OA12316A - 3-Aminoquinazolin-2,4-dione antibacterial agents. - Google Patents

3-Aminoquinazolin-2,4-dione antibacterial agents. Download PDF

Info

Publication number: OA12316A
Authority: OA; OAPI
Prior art keywords: amino; dione; cyclopropyl; fluoro; quinazoline
Prior art date: 2000-01-24

Application number

OA1200200210A

Other languages

English (en)

Inventor

Paul Bird

Edmund Lee Ellsworth

Dai Quoc Nguyen

Joseph Peter Sanchez

Howard Daniel Hollis Showalter

Rajeshwar Singh

Michael Andrew Stier

Tuan Phong Tran

Brian Morgan Watson

Judy Yip

Original Assignee

Warner Lambert Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2000-01-24

Filing date

2000-12-12

Publication date

2006-05-15

2000-12-12 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

2006-05-15 Publication of OA12316A publication Critical patent/OA12316A/en

Links

NMGODFWGUBLTTA-UHFFFAOYSA-N 3-amino-1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)N(N)C(=O)NC2=C1 NMGODFWGUBLTTA-UHFFFAOYSA-N 0.000 title abstract description 14
239000003242 anti bacterial agent Substances 0.000 title description 7
125000000217 alkyl group Chemical group 0.000 claims abstract description 69
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 57
125000003118 aryl group Chemical group 0.000 claims abstract description 48
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 31
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 31
125000000304 alkynyl group Chemical group 0.000 claims abstract description 24
239000001257 hydrogen Substances 0.000 claims abstract description 24
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 24
125000003342 alkenyl group Chemical group 0.000 claims abstract description 22
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 12
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims abstract description 9
229910052799 carbon Inorganic materials 0.000 claims abstract description 9
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract 6
150000001875 compounds Chemical class 0.000 claims description 310
-1 wherein n is 0 or 1 Chemical group 0.000 claims description 193
239000000203 mixture Substances 0.000 claims description 94
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 88
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 68
239000004202 carbamide Substances 0.000 claims description 56
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 51
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 48
125000000547 substituted alkyl group Chemical group 0.000 claims description 41
125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 37
125000005017 substituted alkenyl group Chemical group 0.000 claims description 31
SDQJTWBNWQABLE-UHFFFAOYSA-N 1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)NC2=C1 SDQJTWBNWQABLE-UHFFFAOYSA-N 0.000 claims description 30
125000005843 halogen group Chemical group 0.000 claims description 29
125000004426 substituted alkynyl group Chemical group 0.000 claims description 29
KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 claims description 26
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 23
ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 23
125000001424 substituent group Chemical group 0.000 claims description 18
125000006710 (C2-C12) alkenyl group Chemical group 0.000 claims description 17
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims description 14
RYECOJGRJDOGPP-UHFFFAOYSA-N Ethylurea Chemical compound CCNC(N)=O RYECOJGRJDOGPP-UHFFFAOYSA-N 0.000 claims description 14
LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 14
208000035143 Bacterial infection Diseases 0.000 claims description 13
208000022362 bacterial infectious disease Diseases 0.000 claims description 13
125000006711 (C2-C12) alkynyl group Chemical group 0.000 claims description 12
229910052717 sulfur Inorganic materials 0.000 claims description 12
241000124008 Mammalia Species 0.000 claims description 11
239000003085 diluting agent Substances 0.000 claims description 10
229910052760 oxygen Inorganic materials 0.000 claims description 10
239000000546 pharmaceutical excipient Substances 0.000 claims description 10
125000003107 substituted aryl group Chemical group 0.000 claims description 9
125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 9
108010054814 DNA Gyrase Proteins 0.000 claims description 7
125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 7
125000004122 cyclic group Chemical group 0.000 claims description 7
125000005842 heteroatom Chemical group 0.000 claims description 7
229910052740 iodine Inorganic materials 0.000 claims description 7
125000004429 atom Chemical group 0.000 claims description 6
230000002401 inhibitory effect Effects 0.000 claims description 6
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 4
229910052700 potassium Inorganic materials 0.000 claims description 4
RXUIXCIKQDTZBQ-UHFFFAOYSA-N 1-cyclopropylquinazoline-2,4-dione Chemical compound C1(CC1)N1C(NC(C2=CC=CC=C12)=O)=O RXUIXCIKQDTZBQ-UHFFFAOYSA-N 0.000 claims description 3
XMIQMMOCQFIYFM-UHFFFAOYSA-N pyrrolidine-3-carboxylic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C1CCNC1 XMIQMMOCQFIYFM-UHFFFAOYSA-N 0.000 claims description 3
XJLSEXAGTJCILF-RXMQYKEDSA-N (R)-nipecotic acid zwitterion Chemical compound OC(=O)[C@@H]1CCCNC1 XJLSEXAGTJCILF-RXMQYKEDSA-N 0.000 claims description 2
ZGCGNTZEVIIFAM-UHFFFAOYSA-N 1-fluoro-8-methylquinazoline-2,4-dione Chemical compound FN1C(=O)NC(=O)C2=C1C(C)=CC=C2 ZGCGNTZEVIIFAM-UHFFFAOYSA-N 0.000 claims description 2
NUZLMAGOIPFPSG-UHFFFAOYSA-N 3-amino-1-cyclopropyl-6-fluoro-7-[3-(2-hydroxypropan-2-yl)pyrrolidin-1-yl]-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCC(C(C)(C)O)C1 NUZLMAGOIPFPSG-UHFFFAOYSA-N 0.000 claims description 2
FPGPDSXCAGDSCS-UHFFFAOYSA-N 3-amino-7-(7-amino-5-methyl-3-azabicyclo[3.2.0]heptan-3-yl)-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound COC1=C(N2CC3(C)CC(N)C3C2)C(F)=CC(C(N(N)C2=O)=O)=C1N2C1CC1 FPGPDSXCAGDSCS-UHFFFAOYSA-N 0.000 claims description 2
QWFJOUZUSNZNMP-FOIQADDNSA-N 3-amino-7-[(3r)-3-[(1s)-1-amino-2-phenoxyethyl]pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound C([C@@H](N)[C@@H]1CCN(C1)C1=C(C2=C(C(N(N)C(=O)N2C2CC2)=O)C=C1F)C)OC1=CC=CC=C1 QWFJOUZUSNZNMP-FOIQADDNSA-N 0.000 claims description 2
QCDOITHYWYGQQG-XHSDSOJGSA-N 3-amino-7-[(3r,4s)-3-[(1s)-1-amino-3-methoxypropyl]-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-8-methylquinazoline-2,4-dione Chemical compound C1[C@@H](F)[C@@H]([C@@H](N)CCOC)CN1C1=CC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C QCDOITHYWYGQQG-XHSDSOJGSA-N 0.000 claims description 2
FKEICTOGGGAVEH-ZETCQYMHSA-N 3-amino-7-[(3s)-3-aminopyrrolidin-1-yl]-1-cyclopropyl-6-fluoropyrido[2,3-d]pyrimidine-2,4-dione Chemical compound C1[C@@H](N)CCN1C(C(=C1)F)=NC2=C1C(=O)N(N)C(=O)N2C1CC1 FKEICTOGGGAVEH-ZETCQYMHSA-N 0.000 claims description 2
RXYNGNBFBLYGSY-UHFFFAOYSA-N 3-amino-7-[2-(aminomethyl)-1,3-thiazol-4-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(C)=C1C1=CSC(CN)=N1 RXYNGNBFBLYGSY-UHFFFAOYSA-N 0.000 claims description 2
VLPCEPGNRLOKKI-UHFFFAOYSA-N 3-amino-7-[2-(aminomethyl)-1,3-thiazol-4-yl]-8-chloro-1-cyclopropyl-6-fluoroquinazoline-2,4-dione Chemical compound S1C(CN)=NC(C=2C(=C3C(C(N(N)C(=O)N3C3CC3)=O)=CC=2F)Cl)=C1 VLPCEPGNRLOKKI-UHFFFAOYSA-N 0.000 claims description 2
ZFFKHRCQSMRYSW-UHFFFAOYSA-N 3-amino-7-[3-(1-aminoethyl)-4-methylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CC(C)C(C(C)N)C1 ZFFKHRCQSMRYSW-UHFFFAOYSA-N 0.000 claims description 2
KURNMRMNDDYRKZ-UHFFFAOYSA-N 3-amino-7-[3-(1-aminoethyl)piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCCC(C(C)N)C1 KURNMRMNDDYRKZ-UHFFFAOYSA-N 0.000 claims description 2
DIPPDJOOYUFWLO-UHFFFAOYSA-N 3-amino-7-[3-(2-aminopropan-2-yl)-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-8-methylpyrido[4,3-d]pyrimidine-2,4-dione Chemical compound CC1=C(N2CC(C(F)C2)C(C)(C)N)N=CC(C(N(N)C2=O)=O)=C1N2C1CC1 DIPPDJOOYUFWLO-UHFFFAOYSA-N 0.000 claims description 2
RPBSNJWGNSKHOM-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)-3-(methoxymethyl)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound C1C(COC)(CN)CCN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C RPBSNJWGNSKHOM-UHFFFAOYSA-N 0.000 claims description 2
LFARSGUVNIPJGM-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)-3-methylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoropyrido[2,3-d]pyrimidine-2,4-dione Chemical compound C1C(C)(CN)CCN1C(C(=C1)F)=NC2=C1C(=O)N(N)C(=O)N2C1CC1 LFARSGUVNIPJGM-UHFFFAOYSA-N 0.000 claims description 2
BWXHDANGZXHVDO-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)phenyl]-8-chloro-1-cyclopropyl-6-fluoroquinazoline-2,4-dione Chemical compound NCC1=CC=CC(C=2C(=C3C(C(N(N)C(=O)N3C3CC3)=O)=CC=2F)Cl)=C1 BWXHDANGZXHVDO-UHFFFAOYSA-N 0.000 claims description 2
KMOXXHGLMKCGRK-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)piperidin-1-yl]-1-cyclopropyl-6-fluoropyrido[2,3-d]pyrimidine-2,4-dione Chemical compound C1C(CN)CCCN1C(C(=C1)F)=NC2=C1C(=O)N(N)C(=O)N2C1CC1 KMOXXHGLMKCGRK-UHFFFAOYSA-N 0.000 claims description 2
YSWSMAOIADXSJJ-UHFFFAOYSA-N 3-amino-7-[4-(1-aminoethyl)-3,3-difluoropyrrolidin-1-yl]-1-cyclopropyl-8-methylquinazoline-2,4-dione Chemical compound C1C(F)(F)C(C(N)C)CN1C1=CC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C YSWSMAOIADXSJJ-UHFFFAOYSA-N 0.000 claims description 2
UJHMHUJNQOUEMM-UHFFFAOYSA-N 3-amino-7-[4-(2-aminopropan-2-yl)-3,3-difluoropyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(C)=C1N1CC(C(C)(C)N)C(F)(F)C1 UJHMHUJNQOUEMM-UHFFFAOYSA-N 0.000 claims description 2
HJUIXGXPYMFZOH-UHFFFAOYSA-N 3-amino-7-[4-(2-aminopropan-2-yl)-3,3-difluoropyrrolidin-1-yl]-1-cyclopropyl-8-methylquinazoline-2,4-dione Chemical compound CC1=C(N2CC(F)(F)C(C(C)(C)N)C2)C=CC(C(N(N)C2=O)=O)=C1N2C1CC1 HJUIXGXPYMFZOH-UHFFFAOYSA-N 0.000 claims description 2
VWQSCDFRKGGQGQ-UHFFFAOYSA-N 3-amino-7-[4-(aminomethyl)-3,3-difluoropyrrolidin-1-yl]-1-cyclopropyl-8-methoxyquinazoline-2,4-dione Chemical compound COC1=C(N2CC(F)(F)C(CN)C2)C=CC(C(N(N)C2=O)=O)=C1N2C1CC1 VWQSCDFRKGGQGQ-UHFFFAOYSA-N 0.000 claims description 2
125000003386 piperidinyl group Chemical group 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 10
125000004193 piperazinyl group Chemical group 0.000 claims 2
125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 1
ILSRMENRGMPIHQ-UHFFFAOYSA-N 1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound CC1=CC(F)=CC(C(NC2=O)=O)=C1N2C1CC1 ILSRMENRGMPIHQ-UHFFFAOYSA-N 0.000 claims 1
QGOYJSXAFAHEOQ-UHFFFAOYSA-N 1-cyclopropyl-6-fluoroquinazoline-2,4-dione Chemical compound O=C1NC(=O)C2=CC(F)=CC=C2N1C1CC1 QGOYJSXAFAHEOQ-UHFFFAOYSA-N 0.000 claims 1
125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
GTRJJQDFRZCWKQ-NXEZZACHSA-N 3-amino-1-cyclopropyl-6-fluoro-7-[(3r)-3-[(1r)-1-(methylamino)ethyl]pyrrolidin-1-yl]pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound C1[C@H]([C@@H](C)NC)CCN1C(C(=C1)F)=NC2=C1C(=O)N(N)C(=O)N2C1CC1 GTRJJQDFRZCWKQ-NXEZZACHSA-N 0.000 claims 1
VLVSORUTOYXYIG-UHFFFAOYSA-N 3-amino-7-(2-amino-5-azaspiro[2.4]heptan-5-yl)-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N(C1)CCC21CC2N VLVSORUTOYXYIG-UHFFFAOYSA-N 0.000 claims 1
QBAYAKOQUGQOHL-UHFFFAOYSA-N 3-amino-7-(3-amino-3-methylpyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(C)=C1N1CCC(C)(N)C1 QBAYAKOQUGQOHL-UHFFFAOYSA-N 0.000 claims 1
NICJESYMFMNVRX-UHFFFAOYSA-N 3-amino-7-(3-amino-3-phenylpyrrolidin-1-yl)-8-chloro-1-cyclopropyl-6-fluoroquinazoline-2,4-dione Chemical compound C12=C(Cl)C(N3CC(N)(CC3)C=3C=CC=CC=3)=C(F)C=C2C(=O)N(N)C(=O)N1C1CC1 NICJESYMFMNVRX-UHFFFAOYSA-N 0.000 claims 1
MYNASXNPNLIHST-UHFFFAOYSA-N 3-amino-7-(3-amino-4-fluoropyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CC(N)C(F)C1 MYNASXNPNLIHST-UHFFFAOYSA-N 0.000 claims 1
LMKZWBWISAEVOS-UHFFFAOYSA-N 3-amino-7-(3-amino-4-methoxypyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound C1C(N)C(OC)CN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1OC LMKZWBWISAEVOS-UHFFFAOYSA-N 0.000 claims 1
SMRJEBDYHBYSSD-UHFFFAOYSA-N 3-amino-7-(3-aminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-2,4-dioxoquinazoline-8-carbonitrile Chemical compound C1C(N)CCN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C#N SMRJEBDYHBYSSD-UHFFFAOYSA-N 0.000 claims 1
LXAOHWSBPOQFAW-UHFFFAOYSA-N 3-amino-7-(3-aminopyrrolidin-1-yl)-8-chloro-1-(cyclobutylamino)-6-fluoroquinazoline-2,4-dione Chemical compound C1C(N)CCN1C1=C(F)C=C2C(=O)N(N)C(=O)N(NC3CCC3)C2=C1Cl LXAOHWSBPOQFAW-UHFFFAOYSA-N 0.000 claims 1
USGOLBXMHMCSCB-UHFFFAOYSA-N 3-amino-7-(6-amino-3-azabicyclo[3.1.0]hexan-3-yl)-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound CC1=C(N2CC3C(N)C3C2)C(F)=CC(C(N(N)C2=O)=O)=C1N2C1CC1 USGOLBXMHMCSCB-UHFFFAOYSA-N 0.000 claims 1
WAKUORIXGDVWOW-KUHUBIRLSA-N 3-amino-7-[(3r)-3-[(1r)-1-amino-2-phenoxyethyl]pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound C([C@H](N)[C@@H]1CCN(C1)C1=C(C2=C(C(N(N)C(=O)N2C2CC2)=O)C=C1F)OC)OC1=CC=CC=C1 WAKUORIXGDVWOW-KUHUBIRLSA-N 0.000 claims 1
QZESCCOXPDVVLW-IUODEOHRSA-N 3-amino-7-[(3r)-3-[(1s)-1-amino-2-ethoxyethyl]pyrrolidin-1-yl]-1-cyclopropyl-8-methoxyquinazoline-2,4-dione Chemical compound C1[C@H]([C@H](N)COCC)CCN1C1=CC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1OC QZESCCOXPDVVLW-IUODEOHRSA-N 0.000 claims 1
QCDOITHYWYGQQG-HRCADAONSA-N 3-amino-7-[(3r,4r)-3-[(1r)-1-amino-3-methoxypropyl]-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-8-methylquinazoline-2,4-dione Chemical compound C1[C@H](F)[C@@H]([C@H](N)CCOC)CN1C1=CC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C QCDOITHYWYGQQG-HRCADAONSA-N 0.000 claims 1
WTYRDLVCSKPCMR-VBNZEHGJSA-N 3-amino-7-[(3r,4r)-3-[(1r)-1-amino-3-methoxypropyl]-4-methylpyrrolidin-1-yl]-1-cyclopropyl-8-methoxyquinazoline-2,4-dione Chemical compound C1[C@H](C)[C@@H]([C@H](N)CCOC)CN1C1=CC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1OC WTYRDLVCSKPCMR-VBNZEHGJSA-N 0.000 claims 1
NIHCENZIYVQPQI-AFAVFJNCSA-N 3-amino-7-[(3r,4r)-3-[(1r)-1-amino-3-methoxypropyl]-4-methylpyrrolidin-1-yl]-1-cyclopropyl-8-methylquinazoline-2,4-dione Chemical compound C1[C@H](C)[C@@H]([C@H](N)CCOC)CN1C1=CC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C NIHCENZIYVQPQI-AFAVFJNCSA-N 0.000 claims 1
DMVCNEPYSFWQBP-WQAKAFBOSA-N 3-amino-7-[(3r,4r)-3-[(1r)-1-aminoethyl]-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-8-methoxyquinazoline-2,4-dione Chemical compound COC1=C(N2C[C@@H]([C@@H](F)C2)[C@@H](C)N)C=CC(C(N(N)C2=O)=O)=C1N2C1CC1 DMVCNEPYSFWQBP-WQAKAFBOSA-N 0.000 claims 1
JNBFVIXMWYHESF-HZUKXOBISA-N 3-amino-7-[(3r,4r)-3-[(1s)-1-amino-2-ethoxyethyl]-4-methylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound C1[C@H](C)[C@@H]([C@H](N)COCC)CN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1OC JNBFVIXMWYHESF-HZUKXOBISA-N 0.000 claims 1
DLJALTOFOUWOSY-WCQYABFASA-N 3-amino-7-[(3r,4s)-3-(2-aminopropan-2-yl)-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1C[C@@H](F)[C@@H](C(C)(C)N)C1 DLJALTOFOUWOSY-WCQYABFASA-N 0.000 claims 1
MOZUHBQCTICBJN-ZNMIVQPWSA-N 3-amino-7-[(3r,4s)-3-[(1r)-1-amino-2-ethoxyethyl]-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-8-methoxyquinazoline-2,4-dione Chemical compound C1[C@@H](F)[C@@H]([C@@H](N)COCC)CN1C1=CC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1OC MOZUHBQCTICBJN-ZNMIVQPWSA-N 0.000 claims 1
UQDOBNTYFUNMNV-ZNMIVQPWSA-N 3-amino-7-[(3r,4s)-3-[(1r)-1-amino-2-methoxyethyl]-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-8-methylquinazoline-2,4-dione Chemical compound C1[C@@H](F)[C@@H]([C@@H](N)COC)CN1C1=CC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C UQDOBNTYFUNMNV-ZNMIVQPWSA-N 0.000 claims 1
WCWSUFKBVHIJCI-IMJJTQAJSA-N 3-amino-7-[(3r,4s)-3-[(1s)-1-amino-3-methoxypropyl]-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound C1[C@@H](F)[C@@H]([C@@H](N)CCOC)CN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C WCWSUFKBVHIJCI-IMJJTQAJSA-N 0.000 claims 1
BIXIMKDTYJERQW-ZNMIVQPWSA-N 3-amino-7-[(3r,4s)-3-[(1s)-1-amino-3-methoxypropyl]-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-8-methoxyquinazoline-2,4-dione Chemical compound C1[C@@H](F)[C@@H]([C@@H](N)CCOC)CN1C1=CC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1OC BIXIMKDTYJERQW-ZNMIVQPWSA-N 0.000 claims 1
KTIHLKDZEVPCMQ-ZLKJLUDKSA-N 3-amino-7-[(3r,4s)-3-[(1s)-1-aminoethyl]-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-8-methylquinazoline-2,4-dione Chemical compound C1[C@@H](F)[C@@H]([C@@H](N)C)CN1C1=CC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C KTIHLKDZEVPCMQ-ZLKJLUDKSA-N 0.000 claims 1
QBEKDHJCXXJSMG-UWVGGRQHSA-N 3-amino-7-[(3s)-3-[(1s)-1-aminoethyl]pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CC[C@H]([C@H](C)N)C1 QBEKDHJCXXJSMG-UWVGGRQHSA-N 0.000 claims 1
XTGWCIGUYCKYEE-CTNGQTDRSA-N 3-amino-7-[(4r)-4-[(1r)-1-amino-2-phenoxyethyl]-3,3-dimethylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound C([C@H](N)[C@H]1CN(CC1(C)C)C1=C(C2=C(C(N(N)C(=O)N2C2CC2)=O)C=C1F)C)OC1=CC=CC=C1 XTGWCIGUYCKYEE-CTNGQTDRSA-N 0.000 claims 1
FEHIBOSQMNCPEA-UHFFFAOYSA-N 3-amino-7-[2-(aminomethyl)-1,3-thiazol-4-yl]-1-cyclopropyl-8-methoxyquinazoline-2,4-dione Chemical compound COC1=C(C=2N=C(CN)SC=2)C=CC(C(N(N)C2=O)=O)=C1N2C1CC1 FEHIBOSQMNCPEA-UHFFFAOYSA-N 0.000 claims 1
RNKBXOPKFRJXLU-UHFFFAOYSA-N 3-amino-7-[2-(aminomethyl)-1,3-thiazol-4-yl]-1-cyclopropyl-8-methylquinazoline-2,4-dione Chemical compound CC1=C(C=2N=C(CN)SC=2)C=CC(C(N(N)C2=O)=O)=C1N2C1CC1 RNKBXOPKFRJXLU-UHFFFAOYSA-N 0.000 claims 1
VGZXYHMCVGVCNU-UHFFFAOYSA-N 3-amino-7-[2-(aminomethyl)-1,3-thiazol-4-yl]-8-chloro-1-cyclopropylquinazoline-2,4-dione Chemical compound S1C(CN)=NC(C=2C(=C3C(C(N(N)C(=O)N3C3CC3)=O)=CC=2)Cl)=C1 VGZXYHMCVGVCNU-UHFFFAOYSA-N 0.000 claims 1
USOBMQHLJRHNHP-UHFFFAOYSA-N 3-amino-7-[3-(1-amino-2-methoxyethyl)-4-methylpyrrolidin-1-yl]-1-cyclopropyl-8-methylpyrido[3,2-d]pyrimidine-2,4-dione Chemical compound C1C(C)C(C(N)COC)CN1C1=CN=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C USOBMQHLJRHNHP-UHFFFAOYSA-N 0.000 claims 1
HNLFBZMCUGLSSV-UHFFFAOYSA-N 3-amino-7-[3-(1-amino-2-phenoxyethyl)-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-8-methylpyrido[3,2-d]pyrimidine-2,4-dione Chemical compound CC1=C(N2CC(C(F)C2)C(N)COC=2C=CC=CC=2)C=NC(C(N(N)C2=O)=O)=C1N2C1CC1 HNLFBZMCUGLSSV-UHFFFAOYSA-N 0.000 claims 1
VMUWOJIAZFRLQI-UHFFFAOYSA-N 3-amino-7-[3-(1-amino-2-phenoxyethyl)pyrrolidin-1-yl]-1-cyclopropyl-8-methylpyrido[3,2-d]pyrimidine-2,4-dione Chemical compound CC1=C(N2CC(CC2)C(N)COC=2C=CC=CC=2)C=NC(C(N(N)C2=O)=O)=C1N2C1CC1 VMUWOJIAZFRLQI-UHFFFAOYSA-N 0.000 claims 1
CFMWTONEDJGNEA-UHFFFAOYSA-N 3-amino-7-[3-(1-aminoethyl)-3-fluoropyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCC(F)(C(C)N)C1 CFMWTONEDJGNEA-UHFFFAOYSA-N 0.000 claims 1
PXDQRBZQWZZZNR-UHFFFAOYSA-N 3-amino-7-[3-(1-aminoethyl)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-5-methylquinazoline-2,4-dione Chemical compound FC1=C(C)C(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCC(C(C)N)C1 PXDQRBZQWZZZNR-UHFFFAOYSA-N 0.000 claims 1
WOVLHNXJEKPFRK-UHFFFAOYSA-N 3-amino-7-[3-(1-aminoethyl)pyrrolidin-1-yl]-1-cyclopropyl-8-methoxy-5-methylquinazoline-2,4-dione Chemical compound COC1=C(N2CC(CC2)C(C)N)C=C(C)C(C(N(N)C2=O)=O)=C1N2C1CC1 WOVLHNXJEKPFRK-UHFFFAOYSA-N 0.000 claims 1
UDZZMBWUJRMXKG-UHFFFAOYSA-N 3-amino-7-[3-(2-aminoethyl)piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(C)=C1N1CCCC(CCN)C1 UDZZMBWUJRMXKG-UHFFFAOYSA-N 0.000 claims 1
YGKAPMCVYQSGRM-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)-3-benzylpyrrolidin-1-yl]-8-chloro-1-cyclopropyl-6-fluoroquinazoline-2,4-dione Chemical compound C1CN(C=2C(=C3C(C(N(N)C(=O)N3C3CC3)=O)=CC=2F)Cl)CC1(CN)CC1=CC=CC=C1 YGKAPMCVYQSGRM-UHFFFAOYSA-N 0.000 claims 1
PFAJJDAMOIXZMN-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)phenyl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound COC1=C(C=2C=C(CN)C=CC=2)C(F)=CC(C(N(N)C2=O)=O)=C1N2C1CC1 PFAJJDAMOIXZMN-UHFFFAOYSA-N 0.000 claims 1
UTYJPVXOAGQZNS-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCCC(CN)C1 UTYJPVXOAGQZNS-UHFFFAOYSA-N 0.000 claims 1
WWJJMIXOFUVRBI-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCC(CN)C1 WWJJMIXOFUVRBI-UHFFFAOYSA-N 0.000 claims 1
YIVGSUPJSMHNEV-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(C)=C1N1CCC(CN)C1 YIVGSUPJSMHNEV-UHFFFAOYSA-N 0.000 claims 1
PKBTXJAYWZVJJY-UHFFFAOYSA-N 3-amino-7-[4-(1-amino-2-methoxyethyl)-3,3-dimethylpyrrolidin-1-yl]-1-cyclopropyl-8-methylpyrido[3,2-d]pyrimidine-2,4-dione Chemical compound C1C(C)(C)C(C(N)COC)CN1C1=CN=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C PKBTXJAYWZVJJY-UHFFFAOYSA-N 0.000 claims 1
OPXSUSIFKCWAAZ-UHFFFAOYSA-N 3-amino-7-[4-(1-aminoethyl)-3,3-difluoropyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CC(C(C)N)C(F)(F)C1 OPXSUSIFKCWAAZ-UHFFFAOYSA-N 0.000 claims 1
WHVDJPHTVKCYDW-UHFFFAOYSA-N 3-amino-7-[4-(1-aminoethyl)-3,3-dimethylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound C1C(C)(C)C(C(N)C)CN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C WHVDJPHTVKCYDW-UHFFFAOYSA-N 0.000 claims 1
UOYOEFMXHJGSRL-UHFFFAOYSA-N 3-amino-7-[4-(2-aminopropan-2-yl)-3,3-difluoropyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CC(C(C)(C)N)C(F)(F)C1 UOYOEFMXHJGSRL-UHFFFAOYSA-N 0.000 claims 1
QILKGBMFMDBJDG-UHFFFAOYSA-N 3-amino-7-[4-(2-aminopropan-2-yl)-3,3-difluoropyrrolidin-1-yl]-8-chloro-1-cyclopropylquinazoline-2,4-dione Chemical compound C1C(F)(F)C(C(C)(N)C)CN1C1=CC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1Cl QILKGBMFMDBJDG-UHFFFAOYSA-N 0.000 claims 1
HVYIEAHRHFOQNA-UHFFFAOYSA-N 3-amino-7-[4-(aminomethyl)-3,3-difluoropyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(C)=C1N1CC(CN)C(F)(F)C1 HVYIEAHRHFOQNA-UHFFFAOYSA-N 0.000 claims 1
UCDQJTZOFJBISG-UHFFFAOYSA-N 3-amino-7-[4-(aminomethyl)-3,3-difluoropyrrolidin-1-yl]-8-chloro-1-cyclopropyl-6-fluoroquinazoline-2,4-dione Chemical compound C1C(F)(F)C(CN)CN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1Cl UCDQJTZOFJBISG-UHFFFAOYSA-N 0.000 claims 1
MAXNCKAGFRGUGY-UHFFFAOYSA-N 3-amino-7-[5-(aminomethyl)thiophen-3-yl]-8-chloro-1-cyclopropyl-6-fluoroquinazoline-2,4-dione Chemical compound S1C(CN)=CC(C=2C(=C3C(C(N(N)C(=O)N3C3CC3)=O)=CC=2F)Cl)=C1 MAXNCKAGFRGUGY-UHFFFAOYSA-N 0.000 claims 1
WFDHXKXFTSQIMG-UHFFFAOYSA-N 8-methyl-1h-quinazoline-2,4-dione Chemical compound N1C(=O)NC(=O)C2=C1C(C)=CC=C2 WFDHXKXFTSQIMG-UHFFFAOYSA-N 0.000 claims 1
125000006539 C12 alkyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
RBVBKJAOONPWHN-UHFFFAOYSA-N COC1=CC(=CC2=C1N(CN=C2)C3CC3)F Chemical compound COC1=CC(=CC2=C1N(CN=C2)C3CC3)F RBVBKJAOONPWHN-UHFFFAOYSA-N 0.000 claims 1
230000000844 anti-bacterial effect Effects 0.000 abstract description 14
150000003839 salts Chemical class 0.000 abstract description 9
125000003545 alkoxy group Chemical group 0.000 abstract description 6
125000004663 dialkyl amino group Chemical group 0.000 abstract description 3
125000001475 halogen functional group Chemical group 0.000 abstract description 2
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 319
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 287
238000007429 general method Methods 0.000 description 230
239000000243 solution Substances 0.000 description 228
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 133
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 132
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 132
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 127
KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 116
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 108
239000002253 acid Substances 0.000 description 107
235000019439 ethyl acetate Nutrition 0.000 description 106
229940093499 ethyl acetate Drugs 0.000 description 104
238000000034 method Methods 0.000 description 91
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 90
238000005481 NMR spectroscopy Methods 0.000 description 74
LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 73
KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 72
238000006243 chemical reaction Methods 0.000 description 69
238000003786 synthesis reaction Methods 0.000 description 69
230000015572 biosynthetic process Effects 0.000 description 68
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 66
239000012267 brine Substances 0.000 description 66
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 66
239000012044 organic layer Substances 0.000 description 63
239000007787 solid Substances 0.000 description 62
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 61
239000011541 reaction mixture Substances 0.000 description 56
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 54
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 50
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 50
150000002148 esters Chemical class 0.000 description 49
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 45
229940086542 triethylamine Drugs 0.000 description 44
WJGKQOLBCQGWAL-UHFFFAOYSA-N 3-amino-1-cyclopropyl-6,7-difluoro-8-methoxyquinazoline-2,4-dione Chemical compound COC1=C(F)C(F)=CC(C(N(N)C2=O)=O)=C1N2C1CC1 WJGKQOLBCQGWAL-UHFFFAOYSA-N 0.000 description 41
239000002904 solvent Substances 0.000 description 39
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 38
150000001412 amines Chemical class 0.000 description 36
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
239000000706 filtrate Substances 0.000 description 35
235000013877 carbamide Nutrition 0.000 description 34
DPANLOTXSNLKIA-UHFFFAOYSA-N 3-amino-1-cyclopropyl-6,7-difluoro-5-methylquinazoline-2,4-dione Chemical compound O=C1N(N)C(=O)C=2C(C)=C(F)C(F)=CC=2N1C1CC1 DPANLOTXSNLKIA-UHFFFAOYSA-N 0.000 description 33
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 33
239000002585 base Substances 0.000 description 31
238000003818 flash chromatography Methods 0.000 description 31
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 30
229920006395 saturated elastomer Polymers 0.000 description 29
239000000284 extract Substances 0.000 description 28
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 26
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 23
235000010233 benzoic acid Nutrition 0.000 description 22
239000000460 chlorine Substances 0.000 description 22
239000003921 oil Substances 0.000 description 21
238000001914 filtration Methods 0.000 description 20
230000002829 reductive effect Effects 0.000 description 20
239000005711 Benzoic acid Substances 0.000 description 19
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 19
229960004365 benzoic acid Drugs 0.000 description 19
238000004587 chromatography analysis Methods 0.000 description 19
238000004440 column chromatography Methods 0.000 description 18
230000000694 effects Effects 0.000 description 18
125000006239 protecting group Chemical group 0.000 description 18
235000011121 sodium hydroxide Nutrition 0.000 description 18
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 17
150000001408 amides Chemical class 0.000 description 16
125000004494 ethyl ester group Chemical group 0.000 description 16
229910000104 sodium hydride Inorganic materials 0.000 description 16
229940083608 sodium hydroxide Drugs 0.000 description 16
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
OWIUPIRUAQMTTK-UHFFFAOYSA-N carbazic acid Chemical compound NNC(O)=O OWIUPIRUAQMTTK-UHFFFAOYSA-N 0.000 description 15
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 14
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 14
239000000741 silica gel Substances 0.000 description 14
229910002027 silica gel Inorganic materials 0.000 description 14
229960001866 silicon dioxide Drugs 0.000 description 14
239000012312 sodium hydride Substances 0.000 description 14
VQNBCXNRVVLUKX-UHFFFAOYSA-N 3-amino-7-chloro-1-cyclopropyl-6-fluoropyrido[2,3-d]pyrimidine-2,4-dione Chemical compound C12=NC(Cl)=C(F)C=C2C(=O)N(N)C(=O)N1C1CC1 VQNBCXNRVVLUKX-UHFFFAOYSA-N 0.000 description 13
HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 13
229910052794 bromium Inorganic materials 0.000 description 13
239000003153 chemical reaction reagent Substances 0.000 description 13
239000003795 chemical substances by application Substances 0.000 description 13
238000010992 reflux Methods 0.000 description 13
238000003756 stirring Methods 0.000 description 13
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 12
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
241000588724 Escherichia coli Species 0.000 description 12
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 12
229910000041 hydrogen chloride Inorganic materials 0.000 description 12
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
229910052763 palladium Inorganic materials 0.000 description 12
239000000047 product Substances 0.000 description 12
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 11
239000003054 catalyst Substances 0.000 description 11
229910052801 chlorine Inorganic materials 0.000 description 11
238000001816 cooling Methods 0.000 description 11
150000002923 oximes Chemical class 0.000 description 11
150000007660 quinolones Chemical class 0.000 description 11
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 10
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 10
229960004132 diethyl ether Drugs 0.000 description 10
239000010410 layer Substances 0.000 description 10
239000012038 nucleophile Substances 0.000 description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
238000000746 purification Methods 0.000 description 10
239000007858 starting material Substances 0.000 description 10
239000000725 suspension Substances 0.000 description 10
JWKDABYXHUGBOR-UHFFFAOYSA-N tert-butyl n-amino-n-[2-(cyclopropylamino)-4,5-difluorobenzoyl]carbamate Chemical compound CC(C)(C)OC(=O)N(N)C(=O)C1=CC(F)=C(F)C=C1NC1CC1 JWKDABYXHUGBOR-UHFFFAOYSA-N 0.000 description 10
DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 10
LFIVFMAMROTIED-UHFFFAOYSA-N 3-amino-1-cyclopropyl-6,7-difluoro-8-methylquinazoline-2,4-dione Chemical compound CC1=C(F)C(F)=CC(C(N(N)C2=O)=O)=C1N2C1CC1 LFIVFMAMROTIED-UHFFFAOYSA-N 0.000 description 9
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 9
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 9
239000000463 material Substances 0.000 description 9
239000002244 precipitate Substances 0.000 description 9
150000003235 pyrrolidines Chemical class 0.000 description 9
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 8
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 8
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 8
239000007832 Na2SO4 Substances 0.000 description 8
229960000583 acetic acid Drugs 0.000 description 8
150000001558 benzoic acid derivatives Chemical class 0.000 description 8
244000309464 bull Species 0.000 description 8
229910052731 fluorine Inorganic materials 0.000 description 8
239000000543 intermediate Substances 0.000 description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 0.000 description 8
239000003826 tablet Substances 0.000 description 8
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
238000005160 1H NMR spectroscopy Methods 0.000 description 7
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 7
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
230000001580 bacterial effect Effects 0.000 description 7
238000006555 catalytic reaction Methods 0.000 description 7
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 7
239000007789 gas Substances 0.000 description 7
PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 7
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
239000011734 sodium Substances 0.000 description 7
229910052708 sodium Inorganic materials 0.000 description 7
235000017557 sodium bicarbonate Nutrition 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
239000000758 substrate Substances 0.000 description 7
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
241000894006 Bacteria Species 0.000 description 6
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 6
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 6
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 6
230000008878 coupling Effects 0.000 description 6
238000010168 coupling process Methods 0.000 description 6
238000005859 coupling reaction Methods 0.000 description 6
238000010511 deprotection reaction Methods 0.000 description 6
235000019253 formic acid Nutrition 0.000 description 6
229940013688 formic acid Drugs 0.000 description 6
239000011521 glass Substances 0.000 description 6
150000004678 hydrides Chemical class 0.000 description 6
239000012948 isocyanate Substances 0.000 description 6
150000002513 isocyanates Chemical class 0.000 description 6
150000002576 ketones Chemical class 0.000 description 6
239000007788 liquid Substances 0.000 description 6
229910052943 magnesium sulfate Inorganic materials 0.000 description 6
235000019341 magnesium sulphate Nutrition 0.000 description 6
239000001632 sodium acetate Substances 0.000 description 6
229960004249 sodium acetate Drugs 0.000 description 6
235000017281 sodium acetate Nutrition 0.000 description 6
MMBZQEWHXIZIMA-UHFFFAOYSA-N 3-(dibenzylamino)-1-ethyl-6,7-difluoroquinazoline-2,4-dione Chemical compound O=C1N(CC)C2=CC(F)=C(F)C=C2C(=O)N1N(CC=1C=CC=CC=1)CC1=CC=CC=C1 MMBZQEWHXIZIMA-UHFFFAOYSA-N 0.000 description 5
UBKQNIHKFMGZBC-UHFFFAOYSA-N 3-(dibenzylamino)-6,7-difluoro-1h-quinazoline-2,4-dione Chemical compound O=C1C=2C=C(F)C(F)=CC=2NC(=O)N1N(CC=1C=CC=CC=1)CC1=CC=CC=C1 UBKQNIHKFMGZBC-UHFFFAOYSA-N 0.000 description 5
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 5
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
230000029936 alkylation Effects 0.000 description 5
238000005804 alkylation reaction Methods 0.000 description 5
150000003936 benzamides Chemical class 0.000 description 5
125000006630 butoxycarbonylamino group Chemical group 0.000 description 5
239000002775 capsule Substances 0.000 description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
239000010949 copper Substances 0.000 description 5
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
229940073584 methylene chloride Drugs 0.000 description 5
RWZYAGGXGHYGMB-UHFFFAOYSA-N o-aminobenzenecarboxylic acid Natural products NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
239000000843 powder Substances 0.000 description 5
150000003141 primary amines Chemical class 0.000 description 5
238000006467 substitution reaction Methods 0.000 description 5
150000003462 sulfoxides Chemical class 0.000 description 5
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 5
DQQJBEAXSOOCPG-ZETCQYMHSA-N tert-butyl n-[(3s)-pyrrolidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1CCNC1 DQQJBEAXSOOCPG-ZETCQYMHSA-N 0.000 description 5
UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 5
QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 4
IFZDYNYZWOBYIG-UHFFFAOYSA-N 2-amino-3-chloro-4,5-difluorobenzoic acid Chemical compound NC1=C(Cl)C(F)=C(F)C=C1C(O)=O IFZDYNYZWOBYIG-UHFFFAOYSA-N 0.000 description 4
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical group C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
239000007868 Raney catalyst Substances 0.000 description 4
229910000564 Raney nickel Inorganic materials 0.000 description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
KFTZCNLLRKFMQH-BYPYZUCNSA-N [(3s)-pyrrolidin-3-yl]carbamic acid Chemical compound OC(=O)N[C@H]1CCNC1 KFTZCNLLRKFMQH-BYPYZUCNSA-N 0.000 description 4
230000002378 acidificating effect Effects 0.000 description 4
CLCQGUABBALPKC-UHFFFAOYSA-N amino-[2-(cyclopropylamino)-4,5-difluorobenzoyl]carbamic acid Chemical compound OC(=O)N(N)C(=O)C1=CC(F)=C(F)C=C1NC1CC1 CLCQGUABBALPKC-UHFFFAOYSA-N 0.000 description 4
UFWCPDSEOVJAEA-UHFFFAOYSA-N amino-[3-chloro-2-(cyclopropylamino)-4,5-difluorobenzoyl]carbamic acid Chemical compound OC(=O)N(N)C(=O)C1=CC(F)=C(F)C(Cl)=C1NC1CC1 UFWCPDSEOVJAEA-UHFFFAOYSA-N 0.000 description 4
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 4
MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 4
150000001559 benzoic acids Chemical class 0.000 description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
WRJWRGBVPUUDLA-UHFFFAOYSA-N chlorosulfonyl isocyanate Chemical compound ClS(=O)(=O)N=C=O WRJWRGBVPUUDLA-UHFFFAOYSA-N 0.000 description 4
229910052681 coesite Inorganic materials 0.000 description 4
229910052906 cristobalite Inorganic materials 0.000 description 4
125000004093 cyano group Chemical group *C#N 0.000 description 4
238000006073 displacement reaction Methods 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
150000004820 halides Chemical class 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
239000008101 lactose Substances 0.000 description 4
150000002924 oxiranes Chemical class 0.000 description 4
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
KFTZCNLLRKFMQH-UHFFFAOYSA-N pyrrolidin-3-ylcarbamic acid Chemical compound OC(=O)NC1CCNC1 KFTZCNLLRKFMQH-UHFFFAOYSA-N 0.000 description 4
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 4
238000010561 standard procedure Methods 0.000 description 4
229910052682 stishovite Inorganic materials 0.000 description 4
QELMUWDFAGEENM-UHFFFAOYSA-N tert-butyl n-(3-phenylpyrrolidin-3-yl)carbamate Chemical compound C=1C=CC=CC=1C1(NC(=O)OC(C)(C)C)CCNC1 QELMUWDFAGEENM-UHFFFAOYSA-N 0.000 description 4
229910052905 tridymite Inorganic materials 0.000 description 4
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 4
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
IRFSXVIRXMYULF-UHFFFAOYSA-N 1,2-dihydroquinoline Chemical compound C1=CC=C2C=CCNC2=C1 IRFSXVIRXMYULF-UHFFFAOYSA-N 0.000 description 3
FVRSGQOZJYBPQI-UHFFFAOYSA-N 1-(cyclopropylmethyl)-3-(dibenzylamino)-6,7-difluoroquinazoline-2,4-dione Chemical compound O=C1N(N(CC=2C=CC=CC=2)CC=2C=CC=CC=2)C(=O)C=2C=C(F)C(F)=CC=2N1CC1CC1 FVRSGQOZJYBPQI-UHFFFAOYSA-N 0.000 description 3
RWFOOMQYIRITHL-UHFFFAOYSA-N 1-methylquinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)N(C)C2=C1 RWFOOMQYIRITHL-UHFFFAOYSA-N 0.000 description 3
AKAMNXFLKYKFOJ-UHFFFAOYSA-N 2,4,5-trifluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(F)C=C1F AKAMNXFLKYKFOJ-UHFFFAOYSA-N 0.000 description 3
DGOZIZVTANAGCA-UHFFFAOYSA-N 2-amino-4,5-difluorobenzoic acid Chemical compound NC1=CC(F)=C(F)C=C1C(O)=O DGOZIZVTANAGCA-UHFFFAOYSA-N 0.000 description 3
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
TZZSQUATPYDROZ-UHFFFAOYSA-N 3-hydroxy-1h-quinazoline-2,4-dione Chemical class C1=CC=C2C(=O)N(O)C(=O)NC2=C1 TZZSQUATPYDROZ-UHFFFAOYSA-N 0.000 description 3
CVOUTLIYRVEJSB-UHFFFAOYSA-N 5-benzyl-5-azaspiro[2.4]heptane-7-carboxamide Chemical compound C1C2(CC2)C(C(=O)N)CN1CC1=CC=CC=C1 CVOUTLIYRVEJSB-UHFFFAOYSA-N 0.000 description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
239000012359 Methanesulfonyl chloride Substances 0.000 description 3
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
150000001350 alkyl halides Chemical class 0.000 description 3
238000005576 amination reaction Methods 0.000 description 3
125000003277 amino group Chemical group 0.000 description 3
HRDCWPUIXQGAAM-UHFFFAOYSA-N amino(benzoyl)carbamic acid Chemical class OC(=O)N(N)C(=O)C1=CC=CC=C1 HRDCWPUIXQGAAM-UHFFFAOYSA-N 0.000 description 3
229910021529 ammonia Inorganic materials 0.000 description 3
235000019270 ammonium chloride Nutrition 0.000 description 3
229960001040 ammonium chloride Drugs 0.000 description 3
235000011114 ammonium hydroxide Nutrition 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
229940054066 benzamide antipsychotics Drugs 0.000 description 3
ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 3
239000011575 calcium Substances 0.000 description 3
229910052791 calcium Inorganic materials 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
230000003197 catalytic effect Effects 0.000 description 3
239000003638 chemical reducing agent Substances 0.000 description 3
RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 3
229960002327 chloral hydrate Drugs 0.000 description 3
238000005660 chlorination reaction Methods 0.000 description 3
125000001309 chloro group Chemical group Cl* 0.000 description 3
229960003405 ciprofloxacin Drugs 0.000 description 3
229910052802 copper Inorganic materials 0.000 description 3
239000012043 crude product Substances 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 3
239000006185 dispersion Substances 0.000 description 3
MLANUBGYWOMWLZ-UHFFFAOYSA-N ethyl 2,3,4-trifluorobenzoate Chemical compound CCOC(=O)C1=CC=C(F)C(F)=C1F MLANUBGYWOMWLZ-UHFFFAOYSA-N 0.000 description 3
CNLWICAPVKYJDJ-UHFFFAOYSA-N ethyl 2,4,5-trifluoro-3-methylbenzoate Chemical compound CCOC(=O)C1=CC(F)=C(F)C(C)=C1F CNLWICAPVKYJDJ-UHFFFAOYSA-N 0.000 description 3
YCDADJUAUJPWHD-UHFFFAOYSA-N ethyl 2,4,5-trifluorobenzoate Chemical compound CCOC(=O)C1=CC(F)=C(F)C=C1F YCDADJUAUJPWHD-UHFFFAOYSA-N 0.000 description 3
UPMFDOIEEUTSQC-UHFFFAOYSA-N ethyl 3-chloro-2,4,5-trifluorobenzoate Chemical compound CCOC(=O)C1=CC(F)=C(F)C(Cl)=C1F UPMFDOIEEUTSQC-UHFFFAOYSA-N 0.000 description 3
239000000796 flavoring agent Substances 0.000 description 3
239000011737 fluorine Substances 0.000 description 3
125000001153 fluoro group Chemical group F* 0.000 description 3
229910052736 halogen Inorganic materials 0.000 description 3
150000002367 halogens Chemical class 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
150000002431 hydrogen Chemical group 0.000 description 3
125000004356 hydroxy functional group Chemical group O* 0.000 description 3
239000003112 inhibitor Substances 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
229910052744 lithium Inorganic materials 0.000 description 3
239000012280 lithium aluminium hydride Substances 0.000 description 3
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 3
230000035772 mutation Effects 0.000 description 3
150000002825 nitriles Chemical class 0.000 description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
125000003367 polycyclic group Chemical group 0.000 description 3
239000011591 potassium Substances 0.000 description 3
JAEIBKXSIXOLOL-UHFFFAOYSA-N pyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)C1CCNC1 JAEIBKXSIXOLOL-UHFFFAOYSA-N 0.000 description 3
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 3
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
239000000126 substance Substances 0.000 description 3
ISTGQSQWSKCNFJ-UHFFFAOYSA-N tert-butyl n-ethylcarbamate Chemical compound CCNC(=O)OC(C)(C)C ISTGQSQWSKCNFJ-UHFFFAOYSA-N 0.000 description 3
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 3
238000004809 thin layer chromatography Methods 0.000 description 3
150000003672 ureas Chemical class 0.000 description 3
229940124024 weight reducing agent Drugs 0.000 description 3
239000002023 wood Substances 0.000 description 3
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 2
KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 2
LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 2
HTURLAGGUMXTAE-UHFFFAOYSA-N 2-(2,4-difluoroanilino)-4,5-difluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(F)C=C1NC1=CC=C(F)C=C1F HTURLAGGUMXTAE-UHFFFAOYSA-N 0.000 description 2
NSTREUWFTAOOKS-UHFFFAOYSA-N 2-fluorobenzoic acid Chemical class OC(=O)C1=CC=CC=C1F NSTREUWFTAOOKS-UHFFFAOYSA-N 0.000 description 2
XJPMPMISIRYKGH-UHFFFAOYSA-N 3-amino-1-cyclopropyl-6-fluoro-7-[3-(2-hydroxypropan-2-yl)pyrrolidin-1-yl]-8-methylquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(C)=C1N1CCC(C(C)(C)O)C1 XJPMPMISIRYKGH-UHFFFAOYSA-N 0.000 description 2
ZRLLSDAIVJNZMQ-UHFFFAOYSA-N 3-amino-1-cyclopropyl-6-fluoro-8-methoxy-7-pyrrolidin-1-ylquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCCC1 ZRLLSDAIVJNZMQ-UHFFFAOYSA-N 0.000 description 2
YVKARDDEPDIMAW-UHFFFAOYSA-N 3-amino-7-(3-amino-3-methylpyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione;hydrochloride Chemical compound Cl.FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(C)=C1N1CCC(C)(N)C1 YVKARDDEPDIMAW-UHFFFAOYSA-N 0.000 description 2
PYMLOGUHBHDDDD-UHFFFAOYSA-N 3-amino-7-(3-amino-4-methoxypyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione;hydrochloride Chemical compound Cl.C1C(N)C(OC)CN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1OC PYMLOGUHBHDDDD-UHFFFAOYSA-N 0.000 description 2
FDBCOOAUGVAZKJ-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione;hydrochloride Chemical compound Cl.FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCCC(CN)C1 FDBCOOAUGVAZKJ-UHFFFAOYSA-N 0.000 description 2
JQKQPGZGGHLAGC-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione;hydrochloride Chemical compound Cl.FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(C)=C1N1CCCC(CN)C1 JQKQPGZGGHLAGC-UHFFFAOYSA-N 0.000 description 2
JASKKDJDJMQUCW-UHFFFAOYSA-N 3-amino-7-[4-(aminomethyl)piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCC(CN)CC1 JASKKDJDJMQUCW-UHFFFAOYSA-N 0.000 description 2
ICWQWMNAYJVMHJ-UHFFFAOYSA-N 3-amino-7-[4-(aminomethyl)piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione;hydrochloride Chemical compound Cl.FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCC(CN)CC1 ICWQWMNAYJVMHJ-UHFFFAOYSA-N 0.000 description 2
KBESHLYCSZINAJ-UHFFFAOYSA-N 3-chloro-2,4,5-trifluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(F)C(Cl)=C1F KBESHLYCSZINAJ-UHFFFAOYSA-N 0.000 description 2
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
NBSLFEKLBGUUEA-UHFFFAOYSA-N 3-ethyl-2,4,5-trifluorobenzamide Chemical compound CCC1=C(F)C(F)=CC(C(N)=O)=C1F NBSLFEKLBGUUEA-UHFFFAOYSA-N 0.000 description 2
MXNBDFWNYRNIBH-UHFFFAOYSA-N 3-fluorobenzoic acid Chemical compound OC(=O)C1=CC=CC(F)=C1 MXNBDFWNYRNIBH-UHFFFAOYSA-N 0.000 description 2
ZQQSRVPOAHYHEL-UHFFFAOYSA-N 4-bromo-2-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C=C1F ZQQSRVPOAHYHEL-UHFFFAOYSA-N 0.000 description 2
TUXYZHVUPGXXQG-UHFFFAOYSA-N 4-bromobenzoic acid Chemical class OC(=O)C1=CC=C(Br)C=C1 TUXYZHVUPGXXQG-UHFFFAOYSA-N 0.000 description 2
PMHWMWJIEAQCPA-UHFFFAOYSA-N 5-amino-8,9-difluoro-3-methyl-2,3-dihydro-1-oxa-3a,5-diazaphenalene-4,6-dione Chemical compound O1CC(C)N2C(=O)N(N)C(=O)C3=C2C1=C(F)C(F)=C3 PMHWMWJIEAQCPA-UHFFFAOYSA-N 0.000 description 2
PRAZATCEOJHMET-UHFFFAOYSA-N 5-benzyl-5-azaspiro[2.4]heptane-7-carboxylic acid Chemical compound C1C2(CC2)C(C(=O)O)CN1CC1=CC=CC=C1 PRAZATCEOJHMET-UHFFFAOYSA-N 0.000 description 2
NQNNGQFUHXZUQQ-UHFFFAOYSA-N 7-(1,2,3,4,4a,5,7,7a-octahydropyrrolo[3,4-b]pyridin-6-yl)-3-amino-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione;hydrochloride Chemical compound Cl.CC1=C(N2CC3NCCCC3C2)C(F)=CC(C(N(N)C2=O)=O)=C1N2C1CC1 NQNNGQFUHXZUQQ-UHFFFAOYSA-N 0.000 description 2
PPWBBORVAVZKHU-UHFFFAOYSA-N 7-(1,3,3a,4,5,6,7,7a-octahydropyrrolo[3,4-c]pyridin-2-yl)-3-amino-1-cyclopropyl-6-fluoropyrido[2,3-d]pyrimidine-2,4-dione Chemical compound C12=NC(N3CC4CNCCC4C3)=C(F)C=C2C(=O)N(N)C(=O)N1C1CC1 PPWBBORVAVZKHU-UHFFFAOYSA-N 0.000 description 2
JOUZPZZMCYIDOW-UHFFFAOYSA-N 8-methoxy-1h-quinazoline-2,4-dione Chemical compound N1C(=O)NC(=O)C2=C1C(OC)=CC=C2 JOUZPZZMCYIDOW-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
241000283690 Bos taurus Species 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
101100063435 Caenorhabditis elegans din-1 gene Proteins 0.000 description 2
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
229910021589 Copper(I) bromide Inorganic materials 0.000 description 2
108010041052 DNA Topoisomerase IV Proteins 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
235000019739 Dicalciumphosphate Nutrition 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
239000002262 Schiff base Substances 0.000 description 2
150000004753 Schiff bases Chemical class 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
241000193996 Streptococcus pyogenes Species 0.000 description 2
AWMVMTVKBNGEAK-UHFFFAOYSA-N Styrene oxide Chemical compound C1OC1C1=CC=CC=C1 AWMVMTVKBNGEAK-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
238000010958 [3+2] cycloaddition reaction Methods 0.000 description 2
PCLHRTFHZMANIS-UHFFFAOYSA-N [3-(methoxymethyl)pyrrolidin-3-yl]methylcarbamic acid Chemical compound OC(=O)NCC1(COC)CCNC1 PCLHRTFHZMANIS-UHFFFAOYSA-N 0.000 description 2
FYJKEHKQUPSJDH-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;potassium Chemical compound [K].C[Si](C)(C)N[Si](C)(C)C FYJKEHKQUPSJDH-UHFFFAOYSA-N 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
150000008065 acid anhydrides Chemical class 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
125000003282 alkyl amino group Chemical group 0.000 description 2
150000001356 alkyl thiols Chemical class 0.000 description 2
229960004050 aminobenzoic acid Drugs 0.000 description 2
239000000908 ammonium hydroxide Substances 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
238000011482 antibacterial activity assay Methods 0.000 description 2
229940088710 antibiotic agent Drugs 0.000 description 2
150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
150000001540 azides Chemical class 0.000 description 2
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
238000007664 blowing Methods 0.000 description 2
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
125000001246 bromo group Chemical group Br* 0.000 description 2
239000000872 buffer Substances 0.000 description 2
239000001506 calcium phosphate Substances 0.000 description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
239000000969 carrier Substances 0.000 description 2
238000004296 chiral HPLC Methods 0.000 description 2
229940110456 cocoa butter Drugs 0.000 description 2
235000019868 cocoa butter Nutrition 0.000 description 2
239000003086 colorant Substances 0.000 description 2
229940125773 compound 10 Drugs 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 2
OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
KZZKOVLJUKWSKX-UHFFFAOYSA-N cyclobutanamine Chemical compound NC1CCC1 KZZKOVLJUKWSKX-UHFFFAOYSA-N 0.000 description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 2
229940038472 dicalcium phosphate Drugs 0.000 description 2
229910000390 dicalcium phosphate Inorganic materials 0.000 description 2
125000006333 difluoro benzoyl group Chemical group 0.000 description 2
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000003814 drug Substances 0.000 description 2
SBHMXBYMQZRRLC-UHFFFAOYSA-N ethyl 2,3,4,5-tetrafluorobenzoate Chemical compound CCOC(=O)C1=CC(F)=C(F)C(F)=C1F SBHMXBYMQZRRLC-UHFFFAOYSA-N 0.000 description 2
GJFOWPZJBADLDJ-UHFFFAOYSA-N ethyl 2,3,4,6-tetrafluorobenzoate Chemical compound CCOC(=O)C1=C(F)C=C(F)C(F)=C1F GJFOWPZJBADLDJ-UHFFFAOYSA-N 0.000 description 2
XTMYIEIMUNPCAN-UHFFFAOYSA-N ethyl 2,3,4-trifluoro-5-methoxybenzoate Chemical compound CCOC(=O)C1=CC(OC)=C(F)C(F)=C1F XTMYIEIMUNPCAN-UHFFFAOYSA-N 0.000 description 2
MBTGWZLPWWAHCU-UHFFFAOYSA-N ethyl 2,3-difluorobenzoate Chemical compound CCOC(=O)C1=CC=CC(F)=C1F MBTGWZLPWWAHCU-UHFFFAOYSA-N 0.000 description 2
IDCQRHBVSOPQSN-UHFFFAOYSA-N ethyl 2,4,5-trifluoro-3-(phenylmethoxyiminomethyl)benzoate Chemical compound CCOC(=O)C1=CC(F)=C(F)C(C=NOCC=2C=CC=CC=2)=C1F IDCQRHBVSOPQSN-UHFFFAOYSA-N 0.000 description 2
ZXFYRSUEOKXKOQ-UHFFFAOYSA-N ethyl 2,4,5-trifluoro-3-methoxybenzoate Chemical compound CCOC(=O)C1=CC(F)=C(F)C(OC)=C1F ZXFYRSUEOKXKOQ-UHFFFAOYSA-N 0.000 description 2
LRIZYRFXKQSOFG-UHFFFAOYSA-N ethyl 2,5-difluoro-4-pyrrolidin-1-ylbenzoate Chemical compound C1=C(F)C(C(=O)OCC)=CC(F)=C1N1CCCC1 LRIZYRFXKQSOFG-UHFFFAOYSA-N 0.000 description 2
SOUAXOGPALPTTC-UHFFFAOYSA-N ethyl 2-methylbenzoate Chemical compound CCOC(=O)C1=CC=CC=C1C SOUAXOGPALPTTC-UHFFFAOYSA-N 0.000 description 2
JEZLFPHQDRWQJL-UHFFFAOYSA-N ethyl 5-benzyl-5-azaspiro[2.4]heptane-7-carboxylate Chemical compound C1C2(CC2)C(C(=O)OCC)CN1CC1=CC=CC=C1 JEZLFPHQDRWQJL-UHFFFAOYSA-N 0.000 description 2
239000012065 filter cake Substances 0.000 description 2
235000019634 flavors Nutrition 0.000 description 2
125000006332 fluoro benzoyl group Chemical group 0.000 description 2
238000009472 formulation Methods 0.000 description 2
125000000524 functional group Chemical group 0.000 description 2
239000008187 granular material Substances 0.000 description 2
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
239000005457 ice water Substances 0.000 description 2
208000015181 infectious disease Diseases 0.000 description 2
239000002198 insoluble material Substances 0.000 description 2
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
JJXINDNYLSMEBI-UHFFFAOYSA-N isocyanato thiohypochlorite Chemical compound ClSN=C=O JJXINDNYLSMEBI-UHFFFAOYSA-N 0.000 description 2
ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 2
239000007937 lozenge Substances 0.000 description 2
229960002510 mandelic acid Drugs 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
150000002739 metals Chemical class 0.000 description 2
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
239000002808 molecular sieve Substances 0.000 description 2
DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 2
IHUQJPKASFTOBM-UHFFFAOYSA-N n-(2,4-dinitrophenyl)hydroxylamine Chemical compound ONC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O IHUQJPKASFTOBM-UHFFFAOYSA-N 0.000 description 2
OWIUPIRUAQMTTK-UHFFFAOYSA-M n-aminocarbamate Chemical compound NNC([O-])=O OWIUPIRUAQMTTK-UHFFFAOYSA-M 0.000 description 2
125000004433 nitrogen atom Chemical group N* 0.000 description 2
230000000269 nucleophilic effect Effects 0.000 description 2
239000004533 oil dispersion Substances 0.000 description 2
YZERDTREOUSUHF-UHFFFAOYSA-N pentafluorobenzoic acid Chemical compound OC(=O)C1=C(F)C(F)=C(F)C(F)=C1F YZERDTREOUSUHF-UHFFFAOYSA-N 0.000 description 2
239000006187 pill Substances 0.000 description 2
125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 2
JMXFIDHNGGWPNG-UHFFFAOYSA-N piperidin-3-ylmethylcarbamic acid Chemical compound OC(=O)NCC1CCCNC1 JMXFIDHNGGWPNG-UHFFFAOYSA-N 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
239000002798 polar solvent Substances 0.000 description 2
235000011056 potassium acetate Nutrition 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
125000004076 pyridyl group Chemical group 0.000 description 2
239000000376 reactant Substances 0.000 description 2
230000009257 reactivity Effects 0.000 description 2
238000006268 reductive amination reaction Methods 0.000 description 2
238000011160 research Methods 0.000 description 2
238000007363 ring formation reaction Methods 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
238000005556 structure-activity relationship Methods 0.000 description 2
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
239000011593 sulfur Substances 0.000 description 2
235000011149 sulphuric acid Nutrition 0.000 description 2
239000000829 suppository Substances 0.000 description 2
QIYOMZXJQAKHEK-UHFFFAOYSA-N tert-butyl n-(3-azabicyclo[3.1.0]hexan-6-yl)carbamate Chemical compound C1NCC2C(NC(=O)OC(C)(C)C)C21 QIYOMZXJQAKHEK-UHFFFAOYSA-N 0.000 description 2
DQQJBEAXSOOCPG-UHFFFAOYSA-N tert-butyl n-pyrrolidin-3-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNC1 DQQJBEAXSOOCPG-UHFFFAOYSA-N 0.000 description 2
RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 2
150000003573 thiols Chemical class 0.000 description 2
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
KVWHWHSWGVDONT-UHFFFAOYSA-N (1,3-dibenzylpyrrolidin-3-yl)methanamine Chemical compound C1CN(CC=2C=CC=CC=2)CC1(CN)CC1=CC=CC=C1 KVWHWHSWGVDONT-UHFFFAOYSA-N 0.000 description 1
GFTOKBJWEVSTOT-UHFFFAOYSA-N (1,3-dibenzylpyrrolidin-3-yl)methylcarbamic acid Chemical compound C1CN(CC=2C=CC=CC=2)CC1(CNC(=O)O)CC1=CC=CC=C1 GFTOKBJWEVSTOT-UHFFFAOYSA-N 0.000 description 1
IVTWOXURFILWFQ-UHFFFAOYSA-N (1-benzyl-3-phenylpyrrolidin-3-yl)carbamic acid Chemical compound C1C(NC(=O)O)(C=2C=CC=CC=2)CCN1CC1=CC=CC=C1 IVTWOXURFILWFQ-UHFFFAOYSA-N 0.000 description 1
BZMMRNKDONDVIB-UHFFFAOYSA-N (1-ethoxycyclopropyl)oxy-trimethylsilane Chemical compound CCOC1(O[Si](C)(C)C)CC1 BZMMRNKDONDVIB-UHFFFAOYSA-N 0.000 description 1
ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 1
UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 1
KPIYLFUXCFFIFT-NTSWFWBYSA-N (1s)-1-[(3r)-pyrrolidin-3-yl]ethanamine Chemical compound C[C@H](N)[C@@H]1CCNC1 KPIYLFUXCFFIFT-NTSWFWBYSA-N 0.000 description 1
GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 description 1
IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 1
YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 1
PQXKWPLDPFFDJP-ZXZARUISSA-N (2r,3s)-2,3-dimethyloxirane Chemical compound C[C@H]1O[C@H]1C PQXKWPLDPFFDJP-ZXZARUISSA-N 0.000 description 1
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 1
WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 1
QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
FNHHVPPSBFQMEL-KQHDFZBMSA-N (3S)-5-N-[(1S,5R)-3-hydroxy-6-bicyclo[3.1.0]hexanyl]-7-N,3-dimethyl-3-phenyl-2H-1-benzofuran-5,7-dicarboxamide Chemical compound CNC(=O)c1cc(cc2c1OC[C@@]2(C)c1ccccc1)C(=O)NC1[C@H]2CC(O)C[C@@H]12 FNHHVPPSBFQMEL-KQHDFZBMSA-N 0.000 description 1
IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 1
OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 description 1
HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 1
MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 1
YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 1
STPKWKPURVSAJF-LJEWAXOPSA-N (4r,5r)-5-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2h-1$l^{6}-benzothiepin-4-ol Chemical compound O[C@H]1C(CCCC)(CCCC)CS(=O)(=O)C2=CC=C(N(C)C)C=C2[C@H]1C(C=C1)=CC=C1OCC(C=C1)=CC=C1C[N+]1(CC2)CCN2CC1 STPKWKPURVSAJF-LJEWAXOPSA-N 0.000 description 1
JQTZIHFAISTLHT-UHFFFAOYSA-N (5-benzyl-5-azaspiro[2.4]heptan-7-yl)methylcarbamic acid Chemical compound C(C1=CC=CC=C1)N1CC2(CC2)C(C1)CNC(O)=O JQTZIHFAISTLHT-UHFFFAOYSA-N 0.000 description 1
DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 1
CZVXEAWVGZTLON-UHFFFAOYSA-N 1,1-dibenzylhydrazine Chemical compound C=1C=CC=CC=1CN(N)CC1=CC=CC=C1 CZVXEAWVGZTLON-UHFFFAOYSA-N 0.000 description 1
GRMVKKKRZAKMGY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinazoline-8-carbonitrile Chemical compound C1NCNC2=C1C=CC=C2C#N GRMVKKKRZAKMGY-UHFFFAOYSA-N 0.000 description 1
FIDRAVVQGKNYQK-UHFFFAOYSA-N 1,2,3,4-tetrahydrotriazine Chemical group C1NNNC=C1 FIDRAVVQGKNYQK-UHFFFAOYSA-N 0.000 description 1
DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
OZXIZRZFGJZWBF-UHFFFAOYSA-N 1,3,5-trimethyl-2-(2,4,6-trimethylphenoxy)benzene Chemical compound CC1=CC(C)=CC(C)=C1OC1=C(C)C=C(C)C=C1C OZXIZRZFGJZWBF-UHFFFAOYSA-N 0.000 description 1
KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 1
LVNFQWOJHYWMBQ-UHFFFAOYSA-N 1,5-difluoro-8-methylquinazoline-2,4-dione Chemical compound FC1=C2C(NC(N(C2=C(C=C1)C)F)=O)=O LVNFQWOJHYWMBQ-UHFFFAOYSA-N 0.000 description 1
LHCGUQIZSLMAKQ-UHFFFAOYSA-N 1-(1-benzyl-4-methylpyrrolidin-3-yl)ethanamine Chemical compound C1C(C)C(C(N)C)CN1CC1=CC=CC=C1 LHCGUQIZSLMAKQ-UHFFFAOYSA-N 0.000 description 1
WLLFFDSRCIVDEH-UHFFFAOYSA-N 1-(1-benzyl-4-methylpyrrolidin-3-yl)ethanone Chemical compound C1C(C(C)=O)C(C)CN1CC1=CC=CC=C1 WLLFFDSRCIVDEH-UHFFFAOYSA-N 0.000 description 1
IMUMZPSUQCFIOJ-UHFFFAOYSA-N 1-(1-benzylpiperidin-3-yl)ethanamine Chemical compound C1C(C(N)C)CCCN1CC1=CC=CC=C1 IMUMZPSUQCFIOJ-UHFFFAOYSA-N 0.000 description 1
RQDVPDBLCOYTCI-UHFFFAOYSA-N 1-(3-amino-1-cyclopropyl-6-fluoro-8-methoxy-2,4-dioxoquinazolin-7-yl)pyrrolidine-3-carboxylic acid Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCC(C(O)=O)C1 RQDVPDBLCOYTCI-UHFFFAOYSA-N 0.000 description 1
IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 1
NAGSSHPUGBWQRA-UHFFFAOYSA-N 1-(4-methylpyrrolidin-3-yl)ethylcarbamic acid Chemical compound OC(=O)NC(C)C1CNCC1C NAGSSHPUGBWQRA-UHFFFAOYSA-N 0.000 description 1
UAVGQMYLETUIIP-UHFFFAOYSA-N 1-(7,8-difluoro-3-methyl-2,3-dihydro-1,4-benzoxazin-4-yl)-2-hydroxyiminoethanone Chemical compound FC1=CC=C2N(C(=O)C=NO)C(C)COC2=C1F UAVGQMYLETUIIP-UHFFFAOYSA-N 0.000 description 1
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 1
WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
QXOGPTXQGKQSJT-UHFFFAOYSA-N 1-amino-4-[4-(3,4-dimethylphenyl)sulfanylanilino]-9,10-dioxoanthracene-2-sulfonic acid Chemical compound Cc1ccc(Sc2ccc(Nc3cc(c(N)c4C(=O)c5ccccc5C(=O)c34)S(O)(=O)=O)cc2)cc1C QXOGPTXQGKQSJT-UHFFFAOYSA-N 0.000 description 1
MYMSJFSOOQERIO-UHFFFAOYSA-N 1-bromodecane Chemical compound CCCCCCCCCCBr MYMSJFSOOQERIO-UHFFFAOYSA-N 0.000 description 1
DCPYEEYKLICNTD-UHFFFAOYSA-N 1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound COC1=CC(F)=CC(C(NC2=O)=O)=C1N2C1CC1 DCPYEEYKLICNTD-UHFFFAOYSA-N 0.000 description 1
AICKJUMULHSZFV-UHFFFAOYSA-N 1-cyclopropyl-6-fluoro-8-methylpyrido[3,2-d]pyrimidine-2,4-dione Chemical compound Cc1cc(F)nc2c1n(C1CC1)c(=O)[nH]c2=O AICKJUMULHSZFV-UHFFFAOYSA-N 0.000 description 1
FJKUXVZCNPTQBC-UHFFFAOYSA-N 1-cyclopropyl-6-fluoropyrido[2,3-d]pyrimidine-2,4-dione hydrochloride Chemical compound Cl.C1(CC1)N1C(NC(C2=C1N=CC(=C2)F)=O)=O FJKUXVZCNPTQBC-UHFFFAOYSA-N 0.000 description 1
NJRFMJLTXLPDTB-UHFFFAOYSA-N 1-cyclopropyl-8-methoxyquinazoline-2,4-dione Chemical compound COC1=CC=CC(C(NC2=O)=O)=C1N2C1CC1 NJRFMJLTXLPDTB-UHFFFAOYSA-N 0.000 description 1
LBGAWTGOQQBAHW-UHFFFAOYSA-N 1-cyclopropyl-8-methylpyrido[4,3-d]pyrimidine-2,4-dione Chemical compound C1(CC1)N1C(NC(C2=C1C(=CN=C2)C)=O)=O LBGAWTGOQQBAHW-UHFFFAOYSA-N 0.000 description 1
IHDQPPKBISAIMZ-UHFFFAOYSA-N 1-cyclopropyl-8-methylquinazoline-2,4-dione Chemical compound CC1=CC=CC(C(NC2=O)=O)=C1N2C1CC1 IHDQPPKBISAIMZ-UHFFFAOYSA-N 0.000 description 1
CVIBKISSHDMEKJ-UHFFFAOYSA-N 1-ethylquinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)N(CC)C2=C1 CVIBKISSHDMEKJ-UHFFFAOYSA-N 0.000 description 1
SPUVOGYIVMHJBP-UHFFFAOYSA-N 1-fluoropyrido[2,3-d]pyrimidine-2,4-dione Chemical compound FN1C(NC(C2=C1N=CC=C2)=O)=O SPUVOGYIVMHJBP-UHFFFAOYSA-N 0.000 description 1
NUADXLCTIFJIAU-UHFFFAOYSA-N 1-hydroxyquinazoline-2,4-dione Chemical class C1=CC=C2C(O)=NC(=O)N(O)C2=C1 NUADXLCTIFJIAU-UHFFFAOYSA-N 0.000 description 1
PABBOSQGQGQPFP-UHFFFAOYSA-N 1-piperidin-3-ylethylcarbamic acid Chemical compound OC(=O)NC(C)C1CCCNC1 PABBOSQGQGQPFP-UHFFFAOYSA-N 0.000 description 1
NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 1
SFKRXQKJTIYUAG-UHFFFAOYSA-N 2,3,4,5-tetrafluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(F)C(F)=C1F SFKRXQKJTIYUAG-UHFFFAOYSA-N 0.000 description 1
JMVKZWLEXQRABZ-UHFFFAOYSA-N 2,3,4,6-tetrafluorobenzoic acid Chemical compound OC(=O)C1=C(F)C=C(F)C(F)=C1F JMVKZWLEXQRABZ-UHFFFAOYSA-N 0.000 description 1
CGMSFYATZQKRJY-UHFFFAOYSA-N 2,3,4-trifluoro-5-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=C(F)C(F)=C1F CGMSFYATZQKRJY-UHFFFAOYSA-N 0.000 description 1
WEPXLRANFJEOFZ-UHFFFAOYSA-N 2,3,4-trifluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C(F)=C1F WEPXLRANFJEOFZ-UHFFFAOYSA-N 0.000 description 1
PQXKWPLDPFFDJP-UHFFFAOYSA-N 2,3-dimethyloxirane Chemical compound CC1OC1C PQXKWPLDPFFDJP-UHFFFAOYSA-N 0.000 description 1
PZVWFNBOISIAIN-UHFFFAOYSA-N 2,4,5-trifluoro-3-formylbenzoic acid Chemical compound OC(=O)C1=CC(F)=C(F)C(C=O)=C1F PZVWFNBOISIAIN-UHFFFAOYSA-N 0.000 description 1
VRGBBPYUJDPXBB-UHFFFAOYSA-N 2,4,5-trifluoro-3-methoxybenzamide Chemical compound COC1=C(F)C(F)=CC(C(N)=O)=C1F VRGBBPYUJDPXBB-UHFFFAOYSA-N 0.000 description 1
FAHOHDHMFSGTMT-UHFFFAOYSA-N 2,4,5-trifluoro-3-methylbenzamide Chemical compound CC1=C(F)C(F)=CC(C(N)=O)=C1F FAHOHDHMFSGTMT-UHFFFAOYSA-N 0.000 description 1
CISXRFRLKWCFJS-UHFFFAOYSA-N 2,4,5-trifluoro-3-methylbenzoic acid Chemical compound CC1=C(F)C(F)=CC(C(O)=O)=C1F CISXRFRLKWCFJS-UHFFFAOYSA-N 0.000 description 1
CEPCPXLLFXPZGW-UHFFFAOYSA-N 2,4-difluoroaniline Chemical compound NC1=CC=C(F)C=C1F CEPCPXLLFXPZGW-UHFFFAOYSA-N 0.000 description 1
ZVYNUGSPFZCYEV-UHFFFAOYSA-N 2,6-dichloro-5-fluoropyridine-3-carboxamide Chemical compound NC(=O)C1=CC(F)=C(Cl)N=C1Cl ZVYNUGSPFZCYEV-UHFFFAOYSA-N 0.000 description 1
WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 description 1
FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 description 1
BESBVPBWOJMGFI-UHFFFAOYSA-N 2-(1-benzylpyrrolidin-3-yl)propan-2-ol Chemical compound C1C(C(C)(O)C)CCN1CC1=CC=CC=C1 BESBVPBWOJMGFI-UHFFFAOYSA-N 0.000 description 1
VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 description 1
QEBYEVQKHRUYPE-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-[(1-methylpyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CN(C)N=C1CN1C(=O)C=C2NN(C=3C(=CC=CC=3)Cl)C(=O)C2=C1CN(C)CC1=CC=CN=C1 QEBYEVQKHRUYPE-UHFFFAOYSA-N 0.000 description 1
CJICCPWSDAXVJW-UHFFFAOYSA-N 2-(butan-2-ylamino)-3-chloro-5-fluorobenzoic acid Chemical compound C(C)(CC)NC1=C(C(=O)O)C=C(C=C1Cl)F CJICCPWSDAXVJW-UHFFFAOYSA-N 0.000 description 1
OQWZYHSXLIDCBB-UHFFFAOYSA-N 2-(cyclobutylamino)-5-fluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=CC=C1NC1CCC1 OQWZYHSXLIDCBB-UHFFFAOYSA-N 0.000 description 1
JZKIUAPWPWPRQJ-UHFFFAOYSA-N 2-(cyclopropylamino)-4,5-difluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(F)C=C1NC1CC1 JZKIUAPWPWPRQJ-UHFFFAOYSA-N 0.000 description 1
OFTKVYGVZHVRMC-UHFFFAOYSA-N 2-(cyclopropylamino)benzoic acid Chemical class OC(=O)C1=CC=CC=C1NC1CC1 OFTKVYGVZHVRMC-UHFFFAOYSA-N 0.000 description 1
NOHCGJVKOIEMCT-UHFFFAOYSA-N 2-(methoxymethyl)prop-2-enoic acid Chemical compound COCC(=C)C(O)=O NOHCGJVKOIEMCT-UHFFFAOYSA-N 0.000 description 1
OURMOWNIJUVJSE-UHFFFAOYSA-N 2-(propan-2-ylamino)benzoic acid Chemical compound CC(C)NC1=CC=CC=C1C(O)=O OURMOWNIJUVJSE-UHFFFAOYSA-N 0.000 description 1
NPHAGMZXMINCCX-ZCFIWIBFSA-N 2-[(3r)-pyrrolidin-3-yl]propan-2-amine Chemical compound CC(C)(N)[C@@H]1CCNC1 NPHAGMZXMINCCX-ZCFIWIBFSA-N 0.000 description 1
PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 1
PAYROHWFGZADBR-UHFFFAOYSA-N 2-[[4-amino-5-(5-iodo-4-methoxy-2-propan-2-ylphenoxy)pyrimidin-2-yl]amino]propane-1,3-diol Chemical compound C1=C(I)C(OC)=CC(C(C)C)=C1OC1=CN=C(NC(CO)CO)N=C1N PAYROHWFGZADBR-UHFFFAOYSA-N 0.000 description 1
VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 description 1
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
LGPVTNAJFDUWLF-UHFFFAOYSA-N 2-amino-4-fluorobenzoic acid Chemical compound NC1=CC(F)=CC=C1C(O)=O LGPVTNAJFDUWLF-UHFFFAOYSA-N 0.000 description 1
VTFCXMNTJYSFIR-UHFFFAOYSA-N 2-amino-5-chloro-4-fluorobenzoic acid Chemical compound NC1=CC(F)=C(Cl)C=C1C(O)=O VTFCXMNTJYSFIR-UHFFFAOYSA-N 0.000 description 1
YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
GFXOJLCHSLSWDG-UHFFFAOYSA-N 2-amino-n',n'-dibenzyl-4,5-difluorobenzohydrazide Chemical compound NC1=CC(F)=C(F)C=C1C(=O)NN(CC=1C=CC=CC=1)CC1=CC=CC=C1 GFXOJLCHSLSWDG-UHFFFAOYSA-N 0.000 description 1
VZMAYQMDXZLZFZ-UHFFFAOYSA-N 2-benzyl-1,3,3a,4,5,6,7,7a-octahydropyrrolo[3,4-c]pyridine Chemical compound C1C2CCNCC2CN1CC1=CC=CC=C1 VZMAYQMDXZLZFZ-UHFFFAOYSA-N 0.000 description 1
QFMLCOCFWWTBLB-UHFFFAOYSA-N 2-benzylpent-2-enoic acid Chemical compound CCC=C(C(O)=O)CC1=CC=CC=C1 QFMLCOCFWWTBLB-UHFFFAOYSA-N 0.000 description 1
DUKAXINRLMKHHN-UHFFFAOYSA-N 2-bromo-3-chloro-4,5-difluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(F)C(Cl)=C1Br DUKAXINRLMKHHN-UHFFFAOYSA-N 0.000 description 1
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
XXUNIGZDNWWYED-UHFFFAOYSA-N 2-methylbenzamide Chemical compound CC1=CC=CC=C1C(N)=O XXUNIGZDNWWYED-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 1
PUNCYPYHZDAAFT-UHFFFAOYSA-N 3,4,6-trifluoro-2-methylbenzamide Chemical compound CC1=C(F)C(F)=CC(F)=C1C(N)=O PUNCYPYHZDAAFT-UHFFFAOYSA-N 0.000 description 1
JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
DFRAKBCRUYUFNT-UHFFFAOYSA-N 3,8-dicyclohexyl-2,4,7,9-tetrahydro-[1,3]oxazino[5,6-h][1,3]benzoxazine Chemical compound C1CCCCC1N1CC(C=CC2=C3OCN(C2)C2CCCCC2)=C3OC1 DFRAKBCRUYUFNT-UHFFFAOYSA-N 0.000 description 1
LZEIMXWKROPIMV-UHFFFAOYSA-N 3-(1-aminoethyl)-3-hydroxypyrrolidine-1-carboxylic acid Chemical compound CC(N)C1(O)CCN(C(O)=O)C1 LZEIMXWKROPIMV-UHFFFAOYSA-N 0.000 description 1
QWOQSUGMSNTWNK-UHFFFAOYSA-N 3-(1-azidoethyl)-3-fluoropyrrolidine-1-carboxylic acid Chemical compound [N-]=[N+]=NC(C)C1(F)CCN(C(O)=O)C1 QWOQSUGMSNTWNK-UHFFFAOYSA-N 0.000 description 1
WOBFUTIRYFVZBC-UHFFFAOYSA-N 3-(aminomethyl)-1-benzylpyrrolidin-3-ol Chemical compound C1C(CN)(O)CCN1CC1=CC=CC=C1 WOBFUTIRYFVZBC-UHFFFAOYSA-N 0.000 description 1
QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
WFOVEDJTASPCIR-UHFFFAOYSA-N 3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-n-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1CNC(C=1)=CC=CC=1C(=O)NCC1=CC=CC=C1C(F)(F)F WFOVEDJTASPCIR-UHFFFAOYSA-N 0.000 description 1
OKGVLNCIQZERRV-UHFFFAOYSA-N 3-amino-1-cyclopropyl-6,7-difluoroquinazoline-2,4-dione Chemical compound C12=CC(F)=C(F)C=C2C(=O)N(N)C(=O)N1C1CC1 OKGVLNCIQZERRV-UHFFFAOYSA-N 0.000 description 1
KZIFDDHQIZBWDZ-UHFFFAOYSA-N 3-amino-1-cyclopropyl-8-ethyl-6,7-difluoroquinazoline-2,4-dione Chemical compound CCC1=C(F)C(F)=CC(C(N(N)C2=O)=O)=C1N2C1CC1 KZIFDDHQIZBWDZ-UHFFFAOYSA-N 0.000 description 1
FBZYWRAYHYNGIY-UHFFFAOYSA-N 3-amino-7-(2-amino-5-azaspiro[2.4]heptan-5-yl)-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione;hydrochloride Chemical compound Cl.FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N(C1)CCC21CC2N FBZYWRAYHYNGIY-UHFFFAOYSA-N 0.000 description 1
ONJJNQNMGCKRBJ-UHFFFAOYSA-N 3-amino-7-(3-amino-3-phenylpyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(C)=C1N(C1)CCC1(N)C1=CC=CC=C1 ONJJNQNMGCKRBJ-UHFFFAOYSA-N 0.000 description 1
HHUCACXDAYMCFA-UHFFFAOYSA-N 3-amino-7-(3-amino-3-phenylpyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione;hydrochloride Chemical compound Cl.FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(C)=C1N(C1)CCC1(N)C1=CC=CC=C1 HHUCACXDAYMCFA-UHFFFAOYSA-N 0.000 description 1
RHLHZJMDAZKSES-UHFFFAOYSA-N 3-amino-7-(3-aminoazetidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CC(N)C1 RHLHZJMDAZKSES-UHFFFAOYSA-N 0.000 description 1
MBXPBQAHLCCZOV-UHFFFAOYSA-N 3-amino-7-(3-aminopyrrolidin-1-yl)-1-cyclopropyl-8-ethoxy-6-fluoroquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OCC)=C1N1CCC(N)C1 MBXPBQAHLCCZOV-UHFFFAOYSA-N 0.000 description 1
UOJAWYVCPKBOKI-UHFFFAOYSA-N 3-amino-7-(3-aminopyrrolidin-1-yl)-1-cyclopropyl-8-ethoxy-6-fluoroquinazoline-2,4-dione;hydrochloride Chemical compound Cl.FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OCC)=C1N1CCC(N)C1 UOJAWYVCPKBOKI-UHFFFAOYSA-N 0.000 description 1
FQNCDXCWYOAOPR-UHFFFAOYSA-N 3-amino-7-(3-aminopyrrolidin-1-yl)-1-cyclopropyl-8-fluoro-6-methoxyquinazoline-2,4-dione;hydrochloride Chemical compound Cl.COC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(F)=C1N1CCC(N)C1 FQNCDXCWYOAOPR-UHFFFAOYSA-N 0.000 description 1
XFCMILOJGNQNJQ-UHFFFAOYSA-N 3-amino-7-(3-aminopyrrolidin-1-yl)-8-chloro-1-(cyclobutylamino)-6-fluoroquinazoline-2,4-dione;hydrochloride Chemical compound Cl.C1C(N)CCN1C1=C(F)C=C2C(=O)N(N)C(=O)N(NC3CCC3)C2=C1Cl XFCMILOJGNQNJQ-UHFFFAOYSA-N 0.000 description 1
IZSIJRQLAKGNBV-UHFFFAOYSA-N 3-amino-7-(3-aminopyrrolidin-1-yl)-8-chloro-1-cyclopropyl-6-fluoroquinazoline-2,4-dione Chemical compound C1C(N)CCN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1Cl IZSIJRQLAKGNBV-UHFFFAOYSA-N 0.000 description 1
UFFBMSWIXMBGJA-UHFFFAOYSA-N 3-amino-7-(4-aminopiperidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCC(N)CC1 UFFBMSWIXMBGJA-UHFFFAOYSA-N 0.000 description 1
IXDMETOHGBEQQB-UHFFFAOYSA-N 3-amino-7-(6-amino-3-azabicyclo[3.1.0]hexan-3-yl)-1-cyclopropyl-6-fluoropyrido[2,3-d]pyrimidine-2,4-dione Chemical compound C1C2C(N)C2CN1C(C(=CC=1C(=O)N(N)C2=O)F)=NC=1N2C1CC1 IXDMETOHGBEQQB-UHFFFAOYSA-N 0.000 description 1
UOCLUTIPDCTUDR-SECBINFHSA-N 3-amino-7-[(3r)-3-(2-aminopropan-2-yl)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoropyrido[2,3-d]pyrimidine-2,4-dione Chemical compound C1[C@H](C(C)(N)C)CCN1C(C(=C1)F)=NC2=C1C(=O)N(N)C(=O)N2C1CC1 UOCLUTIPDCTUDR-SECBINFHSA-N 0.000 description 1
ANKPYIGFKBCEHD-HNCPQSOCSA-N 3-amino-7-[(3r)-3-(2-aminopropan-2-yl)pyrrolidin-1-yl]-1-ethyl-6-fluoroquinazoline-2,4-dione;hydrochloride Chemical compound Cl.FC=1C=C2C(=O)N(N)C(=O)N(CC)C2=CC=1N1CC[C@@H](C(C)(C)N)C1 ANKPYIGFKBCEHD-HNCPQSOCSA-N 0.000 description 1
JWSVHFMSXBFEGF-IAQYHMDHSA-N 3-amino-7-[(3r)-3-[(1r)-1-amino-3-methoxypropyl]pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound C1[C@H]([C@H](N)CCOC)CCN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1OC JWSVHFMSXBFEGF-IAQYHMDHSA-N 0.000 description 1
WAKUORIXGDVWOW-AUUYWEPGSA-N 3-amino-7-[(3r)-3-[(1s)-1-amino-2-phenoxyethyl]pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound C([C@@H](N)[C@@H]1CCN(C1)C1=C(C2=C(C(N(N)C(=O)N2C2CC2)=O)C=C1F)OC)OC1=CC=CC=C1 WAKUORIXGDVWOW-AUUYWEPGSA-N 0.000 description 1
JQGVUOKLHQCJOB-CJNGLKHVSA-N 3-amino-7-[(3r)-3-[(1s)-1-amino-3-methoxypropyl]pyrrolidin-1-yl]-1-cyclopropyl-8-methylquinazoline-2,4-dione Chemical compound C1[C@H]([C@@H](N)CCOC)CCN1C1=CC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C JQGVUOKLHQCJOB-CJNGLKHVSA-N 0.000 description 1
WCWSUFKBVHIJCI-CWRNSKLLSA-N 3-amino-7-[(3r,4r)-3-[(1r)-1-amino-3-methoxypropyl]-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound C1[C@H](F)[C@@H]([C@H](N)CCOC)CN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C WCWSUFKBVHIJCI-CWRNSKLLSA-N 0.000 description 1
JMZBLZXEJZISCQ-XNJJOIOASA-N 3-amino-7-[(3r,4r)-3-[(1r)-1-amino-3-methoxypropyl]-4-methylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound C1[C@H](C)[C@@H]([C@H](N)CCOC)CN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C JMZBLZXEJZISCQ-XNJJOIOASA-N 0.000 description 1
SUCBAXXOPKUWKE-GMSGAONNSA-N 3-amino-7-[(3r,4s)-3-(aminomethyl)-4-(trifluoromethyl)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoropyrido[2,3-d]pyrimidine-2,4-dione Chemical compound C1[C@@H](C(F)(F)F)[C@H](CN)CN1C(C(=C1)F)=NC2=C1C(=O)N(N)C(=O)N2C1CC1 SUCBAXXOPKUWKE-GMSGAONNSA-N 0.000 description 1
YVNCLSOUFPUSBG-IMJJTQAJSA-N 3-amino-7-[(3r,4s)-3-[(1r)-1-amino-2-ethoxyethyl]-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound C1[C@@H](F)[C@@H]([C@@H](N)COCC)CN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C YVNCLSOUFPUSBG-IMJJTQAJSA-N 0.000 description 1
WMMXZMSWPCDHCH-XHSDSOJGSA-N 3-amino-7-[(3r,4s)-3-[(1r)-1-amino-2-ethoxyethyl]-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-8-methylquinazoline-2,4-dione Chemical compound C1[C@@H](F)[C@@H]([C@@H](N)COCC)CN1C1=CC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C WMMXZMSWPCDHCH-XHSDSOJGSA-N 0.000 description 1
BXAJEQNNGNFGRI-CFVMTHIKSA-N 3-amino-7-[(3r,4s)-3-[(1r)-1-amino-2-methoxyethyl]-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound C1[C@@H](F)[C@@H]([C@@H](N)COC)CN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C BXAJEQNNGNFGRI-CFVMTHIKSA-N 0.000 description 1
HWEFAWYJNKYDOP-DGFSRKRXSA-N 3-amino-7-[(3r,4s)-3-[(1r)-1-amino-2-methoxyethyl]-4-methylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound C1[C@@H](C)[C@@H]([C@@H](N)COC)CN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1OC HWEFAWYJNKYDOP-DGFSRKRXSA-N 0.000 description 1
JUHGKXCYUJZZLC-UGFHNGPFSA-N 3-amino-7-[(3r,4s)-3-[(1r)-1-amino-2-methoxyethyl]-4-methylpyrrolidin-1-yl]-1-cyclopropyl-8-methoxyquinazoline-2,4-dione Chemical compound C1[C@@H](C)[C@@H]([C@@H](N)COC)CN1C1=CC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1OC JUHGKXCYUJZZLC-UGFHNGPFSA-N 0.000 description 1
TXNCRGZHDIVKJN-ZCNNSNEGSA-N 3-amino-7-[(3r,4s)-3-[(1r)-1-amino-2-phenoxyethyl]-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-8-methylquinazoline-2,4-dione Chemical compound CC1=C(N2C[C@@H]([C@H](F)C2)[C@@H](N)COC=2C=CC=CC=2)C=CC(C(N(N)C2=O)=O)=C1N2C1CC1 TXNCRGZHDIVKJN-ZCNNSNEGSA-N 0.000 description 1
VVEDUPLRSMQSNY-RFVSGWPVSA-N 3-amino-7-[(3r,4s)-3-[(1r)-1-amino-2-phenoxyethyl]-4-methylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound C([C@H](N)[C@H]1CN(C[C@H]1C)C=1C(=C2C(C(N(N)C(=O)N2C2CC2)=O)=CC=1F)C)OC1=CC=CC=C1 VVEDUPLRSMQSNY-RFVSGWPVSA-N 0.000 description 1
GYWQGQNXCURQEH-NQERJWCQSA-N 3-amino-7-[(3r,4s)-3-[(1r)-1-amino-2-phenoxyethyl]-4-methylpyrrolidin-1-yl]-1-cyclopropyl-8-methylquinazoline-2,4-dione Chemical compound C([C@H](N)[C@H]1CN(C[C@H]1C)C=1C(=C2C(C(N(N)C(=O)N2C2CC2)=O)=CC=1)C)OC1=CC=CC=C1 GYWQGQNXCURQEH-NQERJWCQSA-N 0.000 description 1
WTYRDLVCSKPCMR-KCXAZCMYSA-N 3-amino-7-[(3r,4s)-3-[(1s)-1-amino-3-methoxypropyl]-4-methylpyrrolidin-1-yl]-1-cyclopropyl-8-methoxyquinazoline-2,4-dione Chemical compound C1[C@@H](C)[C@@H]([C@@H](N)CCOC)CN1C1=CC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1OC WTYRDLVCSKPCMR-KCXAZCMYSA-N 0.000 description 1
YHGMEWWKLNOXML-MNOVXSKESA-N 3-amino-7-[(3s)-3-[(1r)-1-aminoethyl]pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-5-methylquinazoline-2,4-dione Chemical compound C1[C@@H]([C@H](N)C)CCN1C(C(=C1C)F)=CC2=C1C(=O)N(N)C(=O)N2C1CC1 YHGMEWWKLNOXML-MNOVXSKESA-N 0.000 description 1
SMONLCFJGCJROJ-MNOVXSKESA-N 3-amino-7-[(3s)-3-[(1r)-1-aminoethyl]pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound C1[C@@H]([C@H](N)C)CCN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C SMONLCFJGCJROJ-MNOVXSKESA-N 0.000 description 1
RVXZTPKDGTVNSL-PRHODGIISA-N 3-amino-7-[(3s,4r)-3-amino-4-methylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1C[C@@H](C)[C@H](N)C1 RVXZTPKDGTVNSL-PRHODGIISA-N 0.000 description 1
GMCPKAWGIVMLBF-ZBFHGGJFSA-N 3-amino-7-[(4r)-4-[(1r)-1-amino-2-ethoxyethyl]-3,3-dimethylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound C1C(C)(C)[C@@H]([C@@H](N)COCC)CN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1OC GMCPKAWGIVMLBF-ZBFHGGJFSA-N 0.000 description 1
QRNGWKNPJGFQPC-SJORKVTESA-N 3-amino-7-[(4r)-4-[(1r)-1-amino-2-ethoxyethyl]-3,3-dimethylpyrrolidin-1-yl]-1-cyclopropyl-8-methylquinazoline-2,4-dione Chemical compound C1C(C)(C)[C@@H]([C@@H](N)COCC)CN1C1=CC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C QRNGWKNPJGFQPC-SJORKVTESA-N 0.000 description 1
SCGINPRZWGNIJN-UYAOXDASSA-N 3-amino-7-[(4r)-4-[(1s)-1-amino-2-phenoxyethyl]-3,3-dimethylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound C([C@@H](N)[C@H]1CN(CC1(C)C)C1=C(C2=C(C(N(N)C(=O)N2C2CC2)=O)C=C1F)OC)OC1=CC=CC=C1 SCGINPRZWGNIJN-UYAOXDASSA-N 0.000 description 1
XHJWTSVTXZXVAI-WOJBJXKFSA-N 3-amino-7-[(4r)-4-[(1s)-1-amino-2-phenoxyethyl]-3,3-dimethylpyrrolidin-1-yl]-1-cyclopropyl-8-methoxyquinazoline-2,4-dione Chemical compound COC1=C(N2CC(C)(C)[C@@H]([C@H](N)COC=3C=CC=CC=3)C2)C=CC(C(N(N)C2=O)=O)=C1N2C1CC1 XHJWTSVTXZXVAI-WOJBJXKFSA-N 0.000 description 1
SAXDOWIIPOHGJK-UHFFFAOYSA-N 3-amino-7-[1-(aminomethyl)-1,3,3a,4,5,6,7,7a-octahydroisoindol-2-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound CC1=C(N2C(C3CCCCC3C2)CN)C(F)=CC(C(N(N)C2=O)=O)=C1N2C1CC1 SAXDOWIIPOHGJK-UHFFFAOYSA-N 0.000 description 1
WZEFJJXSICOLBU-UHFFFAOYSA-N 3-amino-7-[1-(aminomethyl)-3-azabicyclo[3.1.0]hexan-3-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound COC1=C(N2CC3(CN)CC3C2)C(F)=CC(C(N(N)C2=O)=O)=C1N2C1CC1 WZEFJJXSICOLBU-UHFFFAOYSA-N 0.000 description 1
NIPRWNSBKFLTLK-UHFFFAOYSA-N 3-amino-7-[3-(1-amino-2-methoxypropyl)-4-methylpyrrolidin-1-yl]-1-cyclopropyl-8-methylpyrido[4,3-d]pyrimidine-2,4-dione Chemical compound C1C(C)C(C(N)C(C)OC)CN1C1=NC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C NIPRWNSBKFLTLK-UHFFFAOYSA-N 0.000 description 1
HCYKRKVCTRDJIX-UHFFFAOYSA-N 3-amino-7-[3-(1-amino-2-methoxypropyl)pyrrolidin-1-yl]-1-cyclopropyl-8-methylpyrido[4,3-d]pyrimidine-2,4-dione Chemical compound C1C(C(N)C(C)OC)CCN1C1=NC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C HCYKRKVCTRDJIX-UHFFFAOYSA-N 0.000 description 1
UBWYHZMRRKOYGJ-UHFFFAOYSA-N 3-amino-7-[3-(1-amino-2-phenoxyethyl)pyrrolidin-1-yl]-1-cyclopropyl-8-methylpyrido[4,3-d]pyrimidine-2,4-dione Chemical compound CC1=C(N2CC(CC2)C(N)COC=2C=CC=CC=2)N=CC(C(N(N)C2=O)=O)=C1N2C1CC1 UBWYHZMRRKOYGJ-UHFFFAOYSA-N 0.000 description 1
QYHNCGDAXNRFGY-UHFFFAOYSA-N 3-amino-7-[3-(1-aminoethyl)-3-methoxypyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound C1C(OC)(C(C)N)CCN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C QYHNCGDAXNRFGY-UHFFFAOYSA-N 0.000 description 1
KSHGSPOSLMZZAJ-UHFFFAOYSA-N 3-amino-7-[3-(1-aminoethyl)piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione;hydrochloride Chemical compound Cl.FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCCC(C(C)N)C1 KSHGSPOSLMZZAJ-UHFFFAOYSA-N 0.000 description 1
XRJWZFHAORTBPI-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)-3-(fluoromethyl)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoroquinazoline-2,4-dione;hydrochloride Chemical compound Cl.C1C(CN)(CF)CCN1C(C(=C1)F)=CC2=C1C(=O)N(N)C(=O)N2C1CC1 XRJWZFHAORTBPI-UHFFFAOYSA-N 0.000 description 1
IIGRIZUDZAXUNS-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)-3-hydroxypyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCC(O)(CN)C1 IIGRIZUDZAXUNS-UHFFFAOYSA-N 0.000 description 1
XOYHKQSGPPTWAD-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)-3-methylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(C)=C1N1CCC(C)(CN)C1 XOYHKQSGPPTWAD-UHFFFAOYSA-N 0.000 description 1
FDPXWWAQMWLPDR-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)-3-methylpyrrolidin-1-yl]-8-chloro-1-cyclopropyl-6-fluoroquinazoline-2,4-dione Chemical compound C1C(C)(CN)CCN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1Cl FDPXWWAQMWLPDR-UHFFFAOYSA-N 0.000 description 1
WTYPWMXNMZPJCE-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)azetidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CC(CN)C1 WTYPWMXNMZPJCE-UHFFFAOYSA-N 0.000 description 1
NNSUFMUPVLRTEA-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)phenyl]-1-cyclopropyl-8-methoxyquinazoline-2,4-dione Chemical compound COC1=C(C=2C=C(CN)C=CC=2)C=CC(C(N(N)C2=O)=O)=C1N2C1CC1 NNSUFMUPVLRTEA-UHFFFAOYSA-N 0.000 description 1
YADGFMPPTBRCNU-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)phenyl]-8-chloro-1-cyclopropylquinazoline-2,4-dione Chemical compound NCC1=CC=CC(C=2C(=C3C(C(N(N)C(=O)N3C3CC3)=O)=CC=2)Cl)=C1 YADGFMPPTBRCNU-UHFFFAOYSA-N 0.000 description 1
DHZKFGGXIOSWDX-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione;hydrochloride Chemical compound Cl.FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCC(CN)C1 DHZKFGGXIOSWDX-UHFFFAOYSA-N 0.000 description 1
HUXFMNVSPFSMDJ-UHFFFAOYSA-N 3-amino-7-[3-(aminomethyl)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(C)=C1N1CCC(CN)C1 HUXFMNVSPFSMDJ-UHFFFAOYSA-N 0.000 description 1
KPEAZQRJPMJXJT-UHFFFAOYSA-N 3-amino-7-[4-(1-amino-2-ethoxyethyl)-3,3-dimethylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylpyrido[3,2-d]pyrimidine-2,4-dione Chemical compound C1C(C)(C)C(C(N)COCC)CN1C1=C(F)N=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C KPEAZQRJPMJXJT-UHFFFAOYSA-N 0.000 description 1
ODGYFTKNQVXYPX-UHFFFAOYSA-N 3-amino-7-[4-(1-aminoethyl)-3,3-difluoropyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound C1C(F)(F)C(C(N)C)CN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C ODGYFTKNQVXYPX-UHFFFAOYSA-N 0.000 description 1
GVYDJTMGSWNLLQ-UHFFFAOYSA-N 3-amino-7-[4-(1-aminoethyl)-3,3-difluoropyrrolidin-1-yl]-1-cyclopropyl-8-methoxyquinazoline-2,4-dione Chemical compound COC1=C(N2CC(F)(F)C(C(C)N)C2)C=CC(C(N(N)C2=O)=O)=C1N2C1CC1 GVYDJTMGSWNLLQ-UHFFFAOYSA-N 0.000 description 1
FXLFPNNYZRRJCG-UHFFFAOYSA-N 3-amino-7-[4-(1-aminoethyl)-3,3-dimethylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CC(C(C)N)C(C)(C)C1 FXLFPNNYZRRJCG-UHFFFAOYSA-N 0.000 description 1
PIXOZOYGPDFQRN-UHFFFAOYSA-N 3-amino-7-[5-(aminomethyl)thiophen-3-yl]-1-cyclopropyl-8-methoxyquinazoline-2,4-dione Chemical compound COC1=C(C=2C=C(CN)SC=2)C=CC(C(N(N)C2=O)=O)=C1N2C1CC1 PIXOZOYGPDFQRN-UHFFFAOYSA-N 0.000 description 1
AINBVJBQTTZKNW-UHFFFAOYSA-N 3-amino-7-[7-(aminomethyl)-5-azaspiro[2.4]heptan-5-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N(C1)CC(CN)C21CC2 AINBVJBQTTZKNW-UHFFFAOYSA-N 0.000 description 1
ASPRZCFYJNJRGE-UHFFFAOYSA-N 3-amino-7-[7-(aminomethyl)-5-azaspiro[2.4]heptan-5-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(C)=C1N(C1)CC(CN)C21CC2 ASPRZCFYJNJRGE-UHFFFAOYSA-N 0.000 description 1
XHDGVTPMBJEXOC-QXXIUIOUSA-N 3-amino-8-[(3R)-3-[(1S)-1-aminoethyl]pyrrolidin-1-yl]-7-fluoro-12-methyl-1,3-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-triene-2,4-dione Chemical compound C1[C@H]([C@@H](N)C)CCN1C1=C(F)C=C2C(=O)N(N)C(=O)N3C(C)CCC1=C32 XHDGVTPMBJEXOC-QXXIUIOUSA-N 0.000 description 1
LGBHTXIBLKBUKN-GKAPJAKFSA-N 3-amino-8-[(3S)-3-aminopyrrolidin-1-yl]-7-fluoro-12-methyl-1,3-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-triene-2,4-dione Chemical compound FC1=CC(C(N(N)C2=O)=O)=C3N2C(C)CCC3=C1N1CC[C@H](N)C1 LGBHTXIBLKBUKN-GKAPJAKFSA-N 0.000 description 1
AJISAFYWCLOWCA-MTICXXPYSA-N 3-amino-8-[(3S)-3-aminopyrrolidin-1-yl]-7-fluoro-12-methyl-10-oxa-1,3-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-triene-2,4-dione hydrochloride Chemical compound Cl.FC1=CC(C(N(N)C2=O)=O)=C3N2C(C)COC3=C1N1CC[C@H](N)C1 AJISAFYWCLOWCA-MTICXXPYSA-N 0.000 description 1
TYIIMJIDXZWQBV-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexan-1-ylmethylcarbamic acid Chemical compound C1NCC2(CNC(=O)O)C1C2 TYIIMJIDXZWQBV-UHFFFAOYSA-N 0.000 description 1
NSFFUUCTCIWHRO-UHFFFAOYSA-N 3-chloro-2-(cyclopropylamino)-4,5-difluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(F)C(Cl)=C1NC1CC1 NSFFUUCTCIWHRO-UHFFFAOYSA-N 0.000 description 1
FPHNWFFKQCPXPI-UHFFFAOYSA-N 3-chlorooxolane Chemical compound ClC1CCOC1 FPHNWFFKQCPXPI-UHFFFAOYSA-N 0.000 description 1
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
BFJMHTOBRRZELQ-UHFFFAOYSA-N 3-iodo-2h-pyrazolo[3,4-c]pyridine Chemical compound N1=CC=C2C(I)=NNC2=C1 BFJMHTOBRRZELQ-UHFFFAOYSA-N 0.000 description 1
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
HRASFKASEOUOPD-UHFFFAOYSA-N 3-oxopyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCC(=O)C1 HRASFKASEOUOPD-UHFFFAOYSA-N 0.000 description 1
PRRFFTYUBPGHLE-UHFFFAOYSA-N 3-phenylpyrrolidine Chemical compound C1NCCC1C1=CC=CC=C1 PRRFFTYUBPGHLE-UHFFFAOYSA-N 0.000 description 1
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
MPMKMQHJHDHPBE-RUZDIDTESA-N 4-[[(2r)-1-(1-benzothiophene-3-carbonyl)-2-methylazetidine-2-carbonyl]-[(3-chlorophenyl)methyl]amino]butanoic acid Chemical compound O=C([C@@]1(N(CC1)C(=O)C=1C2=CC=CC=C2SC=1)C)N(CCCC(O)=O)CC1=CC=CC(Cl)=C1 MPMKMQHJHDHPBE-RUZDIDTESA-N 0.000 description 1
GSDQYSSLIKJJOG-UHFFFAOYSA-N 4-chloro-2-(3-chloroanilino)benzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1NC1=CC=CC(Cl)=C1 GSDQYSSLIKJJOG-UHFFFAOYSA-N 0.000 description 1
DQAZPZIYEOGZAF-UHFFFAOYSA-N 4-ethyl-n-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]piperazine-1-carboxamide Chemical compound C1CN(CC)CCN1C(=O)NC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=CC(C#C)=C1 DQAZPZIYEOGZAF-UHFFFAOYSA-N 0.000 description 1
KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
VKLKXFOZNHEBSW-UHFFFAOYSA-N 5-[[3-[(4-morpholin-4-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide Chemical compound O1CCN(CC1)C1=CC=C(C(=O)NC=2C=C(COC=3C=NC=C(C(=O)N)C=3)C=CC=2)C=C1 VKLKXFOZNHEBSW-UHFFFAOYSA-N 0.000 description 1
UPSMTUVVGYVRLT-UHFFFAOYSA-N 5-azaspiro[2.4]heptan-7-ylmethylcarbamic acid Chemical compound C1CC11CNCC1CNC(O)=O UPSMTUVVGYVRLT-UHFFFAOYSA-N 0.000 description 1
CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 1
CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
OYWCDOHPMUVCFN-UHFFFAOYSA-N 6-(3-amino-1-cyclopropyl-6-fluoro-8-methyl-2,4-dioxoquinazolin-7-yl)-3,4,4a,5,7,7a-hexahydro-2h-pyrrolo[3,4-b]pyridine-1-carboxylic acid Chemical compound CC1=C(N2CC3N(CCCC3C2)C(O)=O)C(F)=CC(C(N(N)C2=O)=O)=C1N2C1CC1 OYWCDOHPMUVCFN-UHFFFAOYSA-N 0.000 description 1
RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 description 1
GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 description 1
FDEBGCDNOMDORP-UHFFFAOYSA-N 6-fluoro-8-methoxy-1h-quinazoline-2,4-dione Chemical compound N1C(=O)NC(=O)C2=C1C(OC)=CC(F)=C2 FDEBGCDNOMDORP-UHFFFAOYSA-N 0.000 description 1
KGBZCXRJTWRQGJ-UHFFFAOYSA-N 6-fluoro-8-methyl-1h-quinazoline-2,4-dione Chemical compound N1C(=O)NC(=O)C2=C1C(C)=CC(F)=C2 KGBZCXRJTWRQGJ-UHFFFAOYSA-N 0.000 description 1
125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 1
ZZEOFKLXAXVIOD-UHFFFAOYSA-N 7-chloro-1-cyclopropyl-6-fluoropyrido[2,3-d]pyrimidine-2,4-dione Chemical compound N1=C(Cl)C(F)=CC(C(NC2=O)=O)=C1N2C1CC1 ZZEOFKLXAXVIOD-UHFFFAOYSA-N 0.000 description 1
CGEUYSMLTTYJHA-UHFFFAOYSA-N 8,9-difluoro-3-methyl-2,3-dihydro-1-oxa-3a,5-diaza-phenalene-4,6-dione Chemical compound O1CC(C)N2C(=O)NC(=O)C3=C2C1=C(F)C(F)=C3 CGEUYSMLTTYJHA-UHFFFAOYSA-N 0.000 description 1
YPKUTBCKHJBNKX-UHFFFAOYSA-N 8-bromo-5,6-difluoro-2-methylquinoline Chemical compound FC1=C(F)C=C(Br)C2=NC(C)=CC=C21 YPKUTBCKHJBNKX-UHFFFAOYSA-N 0.000 description 1
XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 description 1
IRBAWVGZNJIROV-SFHVURJKSA-N 9-(2-cyclopropylethynyl)-2-[[(2s)-1,4-dioxan-2-yl]methoxy]-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one Chemical compound C1=C2C3=CC=C(C#CC4CC4)C=C3CCN2C(=O)N=C1OC[C@@H]1COCCO1 IRBAWVGZNJIROV-SFHVURJKSA-N 0.000 description 1
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
102000009027 Albumins Human genes 0.000 description 1
108010088751 Albumins Proteins 0.000 description 1
241000768714 Anoides Species 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
IYHHRZBKXXKDDY-UHFFFAOYSA-N BI-605906 Chemical compound N=1C=2SC(C(N)=O)=C(N)C=2C(C(F)(F)CC)=CC=1N1CCC(S(C)(=O)=O)CC1 IYHHRZBKXXKDDY-UHFFFAOYSA-N 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
229910000906 Bronze Inorganic materials 0.000 description 1
JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 description 1
GFSRBYTUPIBSKG-UHFFFAOYSA-N C(C1=CC=CC=C1)N1CC(CC1)(O)CNC(O)=O Chemical compound C(C1=CC=CC=C1)N1CC(CC1)(O)CNC(O)=O GFSRBYTUPIBSKG-UHFFFAOYSA-N 0.000 description 1
XAXVZWFMYBMFHS-BAUSSPIASA-N C(N)(O)=O.OC1=CC=C(C=C1)[C@H]1[C@@H](CNC1)N Chemical compound C(N)(O)=O.OC1=CC=C(C=C1)[C@H]1[C@@H](CNC1)N XAXVZWFMYBMFHS-BAUSSPIASA-N 0.000 description 1
ZWTRWPKVEDPSHZ-UHFFFAOYSA-N C1=CC=C(C=C1)C(=O)N(C(=O)O)NCl Chemical compound C1=CC=C(C=C1)C(=O)N(C(=O)O)NCl ZWTRWPKVEDPSHZ-UHFFFAOYSA-N 0.000 description 1
XNOGOHBFPMEBMF-UHFFFAOYSA-N C1CC1NC2=C(C(=C(C=C2F)F)F)C(=O)O Chemical compound C1CC1NC2=C(C(=C(C=C2F)F)F)C(=O)O XNOGOHBFPMEBMF-UHFFFAOYSA-N 0.000 description 1
KCBAMQOKOLXLOX-BSZYMOERSA-N CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O Chemical compound CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O KCBAMQOKOLXLOX-BSZYMOERSA-N 0.000 description 1
UHNRLQRZRNKOKU-UHFFFAOYSA-N CCN(CC1=NC2=C(N1)C1=CC=C(C=C1N=C2N)C1=NNC=C1)C(C)=O Chemical compound CCN(CC1=NC2=C(N1)C1=CC=C(C=C1N=C2N)C1=NNC=C1)C(C)=O UHNRLQRZRNKOKU-UHFFFAOYSA-N 0.000 description 1
BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 1
PKMUHQIDVVOXHQ-HXUWFJFHSA-N C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O Chemical compound C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O PKMUHQIDVVOXHQ-HXUWFJFHSA-N 0.000 description 1
241000070928 Calligonum comosum Species 0.000 description 1
206010007134 Candida infections Diseases 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
XNTJOEHXFIMRTN-UHFFFAOYSA-N Cl.ClC1=C2C(NC(N(C2=CC=C1F)C1CC1)=O)=O Chemical compound Cl.ClC1=C2C(NC(N(C2=CC=C1F)C1CC1)=O)=O XNTJOEHXFIMRTN-UHFFFAOYSA-N 0.000 description 1
229940126657 Compound 17 Drugs 0.000 description 1
229940126639 Compound 33 Drugs 0.000 description 1
229940127007 Compound 39 Drugs 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
239000004375 Dextrin Substances 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
241000283086 Equidae Species 0.000 description 1
241001302584 Escherichia coli str. K-12 substr. W3110 Species 0.000 description 1
241000495778 Escherichia faecalis Species 0.000 description 1
ZFDIRQKJPRINOQ-HWKANZROSA-N Ethyl crotonate Chemical compound CCOC(=O)\C=C\C ZFDIRQKJPRINOQ-HWKANZROSA-N 0.000 description 1
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 1
229920001917 Ficoll Polymers 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
102100022087 Granzyme M Human genes 0.000 description 1
239000007818 Grignard reagent Substances 0.000 description 1
241000282412 Homo Species 0.000 description 1
101000900697 Homo sapiens Granzyme M Proteins 0.000 description 1
LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
241001024304 Mino Species 0.000 description 1
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-Chlorosuccinimide Substances ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 1
HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 1
POFVJRKJJBFPII-UHFFFAOYSA-N N-cyclopentyl-5-[2-[[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]amino]-5-fluoropyrimidin-4-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound C1(CCCC1)NC=1SC(=C(N=1)C)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1CCN(CC1)CC POFVJRKJJBFPII-UHFFFAOYSA-N 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
FYVBUMABRLOPIH-QRPNPIFTSA-N OC(=O)C(F)(F)F.FC=1C=C2C(=O)N(N)C(=O)N([C@@H](C)CC)C2=C(Cl)C=1N1CCC(N)=C1 Chemical compound OC(=O)C(F)(F)F.FC=1C=C2C(=O)N(N)C(=O)N([C@@H](C)CC)C2=C(Cl)C=1N1CCC(N)=C1 FYVBUMABRLOPIH-QRPNPIFTSA-N 0.000 description 1
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
241001494479 Pecora Species 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
108091000080 Phosphotransferase Proteins 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
239000004743 Polypropylene Substances 0.000 description 1
102100040125 Prokineticin-2 Human genes 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
208000035193 Ring chromosome 10 syndrome Diseases 0.000 description 1
101100391171 Schizosaccharomyces pombe (strain 972 / ATCC 24843) for3 gene Proteins 0.000 description 1
PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 1
241000287181 Sturnus vulgaris Species 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
KZVWEOXAPZXAFB-BQFCYCMXSA-N Temocaprilat Chemical compound C([C@H](N[C@H]1CS[C@@H](CN(C1=O)CC(=O)O)C=1SC=CC=1)C(O)=O)CC1=CC=CC=C1 KZVWEOXAPZXAFB-BQFCYCMXSA-N 0.000 description 1
241000746181 Therates Species 0.000 description 1
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 description 1
101710183280 Topoisomerase Proteins 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
ZAJMGFOHORRQHJ-ZJUUUORDSA-N [(1R)-1-[(3S)-1-(3-amino-1-cyclopropyl-6-fluoro-8-methoxy-2,4-dioxoquinazolin-7-yl)pyrrolidin-3-yl]ethyl]carbamic acid Chemical compound NN1C(N(C2=C(C(=C(C=C2C1=O)F)N1C[C@H](CC1)[C@@H](C)NC(O)=O)OC)C1CC1)=O ZAJMGFOHORRQHJ-ZJUUUORDSA-N 0.000 description 1
LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 1
SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 1
PJUXHXXITBWVGH-ONERCXAPSA-N [(2r)-2-amino-2-[(3r,4s)-1-(3-amino-1-cyclopropyl-8-methyl-2,4-dioxoquinazolin-7-yl)-4-methylpyrrolidin-3-yl]ethyl]urea Chemical compound C1[C@H]([C@@H](N)CNC(N)=O)[C@H](C)CN1C1=CC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C PJUXHXXITBWVGH-ONERCXAPSA-N 0.000 description 1
LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
OBSZOKMCBCLMDG-NXEZZACHSA-N [(3R,4S)-1-(3-amino-1-cyclopropyl-6-fluoro-8-methoxy-2,4-dioxoquinazolin-7-yl)-4-methylpyrrolidin-3-yl]methylcarbamic acid Chemical compound NN1C(N(C2=C(C(=C(C=C2C1=O)F)N1C[C@H]([C@@H](C1)C)CNC(O)=O)OC)C1CC1)=O OBSZOKMCBCLMDG-NXEZZACHSA-N 0.000 description 1
PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 1
VVWWZNABBUHLGV-VXGBXAGGSA-N [(3r,4s)-1-benzyl-4-fluoropyrrolidin-3-yl]methanamine Chemical compound C1[C@@H](F)[C@H](CN)CN1CC1=CC=CC=C1 VVWWZNABBUHLGV-VXGBXAGGSA-N 0.000 description 1
INIFTNJCPUKRNG-WHFBIAKZSA-N [(3s,4r)-4-fluoropyrrolidin-3-yl]methylcarbamic acid Chemical compound OC(=O)NC[C@@H]1CNC[C@@H]1F INIFTNJCPUKRNG-WHFBIAKZSA-N 0.000 description 1
CYLQMANYNUPGOT-RFZPGFLSSA-N [(3s,4r)-4-methylpyrrolidin-3-yl]carbamic acid Chemical compound C[C@@H]1CNC[C@H]1NC(O)=O CYLQMANYNUPGOT-RFZPGFLSSA-N 0.000 description 1
FPVAVBQSEOTFLS-UHFFFAOYSA-N [1-benzyl-3-(methoxymethyl)pyrrolidin-3-yl]methylcarbamic acid Chemical compound C(C1=CC=CC=C1)N1CC(CC1)(COC)CNC(O)=O FPVAVBQSEOTFLS-UHFFFAOYSA-N 0.000 description 1
XKDKVSOGSDWQBN-UHFFFAOYSA-N [7a-(aminomethyl)-3,3a,4,5,6,7-hexahydro-1H-isoindol-2-yl]carbamic acid Chemical compound NCC12CN(CC2CCCC1)NC(O)=O XKDKVSOGSDWQBN-UHFFFAOYSA-N 0.000 description 1
DZJXKISLUDYJSV-UHFFFAOYSA-N [N].C1CCNC1 Chemical compound [N].C1CCNC1 DZJXKISLUDYJSV-UHFFFAOYSA-N 0.000 description 1
SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 1
IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000004913 activation Effects 0.000 description 1
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
239000011543 agarose gel Substances 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
150000001298 alcohols Chemical group 0.000 description 1
QBYJBZPUGVGKQQ-SJJAEHHWSA-N aldrin Chemical compound C1[C@H]2C=C[C@@H]1[C@H]1[C@@](C3(Cl)Cl)(Cl)C(Cl)=C(Cl)[C@@]3(Cl)[C@H]12 QBYJBZPUGVGKQQ-SJJAEHHWSA-N 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
239000003513 alkali Substances 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
150000004703 alkoxides Chemical class 0.000 description 1
125000005262 alkoxyamine group Chemical group 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
125000004414 alkyl thio group Chemical group 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
235000001014 amino acid Nutrition 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
CKYZTGMIVXEZCY-UHFFFAOYSA-N amino-[2-(2,4-difluoroanilino)-4,5-difluorobenzoyl]carbamic acid Chemical compound OC(=O)N(N)C(=O)C1=CC(F)=C(F)C=C1NC1=CC=C(F)C=C1F CKYZTGMIVXEZCY-UHFFFAOYSA-N 0.000 description 1
UASGLPSACCQFHO-UHFFFAOYSA-N amino-[5-chloro-2-(cyclopropylamino)-4-fluorobenzoyl]carbamic acid Chemical compound OC(=O)N(N)C(=O)C1=CC(Cl)=C(F)C=C1NC1CC1 UASGLPSACCQFHO-UHFFFAOYSA-N 0.000 description 1
150000005415 aminobenzoic acids Chemical class 0.000 description 1
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
230000001773 anti-convulsant effect Effects 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
239000001961 anticonvulsive agent Substances 0.000 description 1
229960003965 antiepileptics Drugs 0.000 description 1
239000004599 antimicrobial Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
159000000032 aromatic acids Chemical class 0.000 description 1
150000004982 aromatic amines Chemical class 0.000 description 1
125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
235000021311 artificial sweeteners Nutrition 0.000 description 1
125000001769 aryl amino group Chemical group 0.000 description 1
125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
235000003704 aspartic acid Nutrition 0.000 description 1
238000003556 assay Methods 0.000 description 1
XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
201000001034 autosomal recessive chronic granulomatous disease cytochrome b-positive type III Diseases 0.000 description 1
DLGYNVMUCSTYDQ-UHFFFAOYSA-N azane;pyridine Chemical compound N.C1=CC=NC=C1 DLGYNVMUCSTYDQ-UHFFFAOYSA-N 0.000 description 1
XMQFTWRPUQYINF-UHFFFAOYSA-N bensulfuron-methyl Chemical compound COC(=O)C1=CC=CC=C1CS(=O)(=O)NC(=O)NC1=NC(OC)=CC(OC)=N1 XMQFTWRPUQYINF-UHFFFAOYSA-N 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
229940050390 benzoate Drugs 0.000 description 1
WLPUFAZAMBXLPF-UHFFFAOYSA-N benzyl 2,3,4,5,6-pentafluorobenzoate Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1C(=O)OCC1=CC=CC=C1 WLPUFAZAMBXLPF-UHFFFAOYSA-N 0.000 description 1
IBRANEFDJOMGLV-UHFFFAOYSA-N benzyl 2-methyl-1-oxa-6-azaspiro[2.4]heptane-6-carboxylate Chemical compound CC1OC11CN(C(=O)OCC=2C=CC=CC=2)CC1 IBRANEFDJOMGLV-UHFFFAOYSA-N 0.000 description 1
VZLUBHTWJFSSEX-UHFFFAOYSA-N benzyl 3-(1-aminoethyl)-3-hydroxypyrrolidine-1-carboxylate Chemical compound C1C(C(N)C)(O)CCN1C(=O)OCC1=CC=CC=C1 VZLUBHTWJFSSEX-UHFFFAOYSA-N 0.000 description 1
PRAYTHAYJVDPMX-UHFFFAOYSA-N benzyl 3-(1-aminoethyl)-3-methoxypyrrolidine-1-carboxylate Chemical compound C1C(OC)(C(C)N)CCN1C(=O)OCC1=CC=CC=C1 PRAYTHAYJVDPMX-UHFFFAOYSA-N 0.000 description 1
HNRGJNVEHLTNBK-UHFFFAOYSA-N benzyl 3-fluoro-3-(1-hydroxyethyl)pyrrolidine-1-carboxylate Chemical compound C1C(C(O)C)(F)CCN1C(=O)OCC1=CC=CC=C1 HNRGJNVEHLTNBK-UHFFFAOYSA-N 0.000 description 1
SOVOZYVNLBCFLM-UHFFFAOYSA-N benzyl 3-fluoro-3-(1-methylsulfonyloxyethyl)pyrrolidine-1-carboxylate Chemical compound C1C(C(OS(C)(=O)=O)C)(F)CCN1C(=O)OCC1=CC=CC=C1 SOVOZYVNLBCFLM-UHFFFAOYSA-N 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
125000001743 benzylic group Chemical group 0.000 description 1
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
229910000085 borane Inorganic materials 0.000 description 1
230000031709 bromination Effects 0.000 description 1
238000005893 bromination reaction Methods 0.000 description 1
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
RUEKPBLTWGFBOD-UHFFFAOYSA-N bromoethyne Chemical group BrC#C RUEKPBLTWGFBOD-UHFFFAOYSA-N 0.000 description 1
AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
239000010974 bronze Substances 0.000 description 1
ILAJWURWJKXJPW-UHFFFAOYSA-N butanedioic acid;octanedioic acid Chemical compound OC(=O)CCC(O)=O.OC(=O)CCCCCCC(O)=O ILAJWURWJKXJPW-UHFFFAOYSA-N 0.000 description 1
BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 description 1
239000000292 calcium oxide Substances 0.000 description 1
ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 1
239000007963 capsule composition Substances 0.000 description 1
125000001589 carboacyl group Chemical group 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
229910002091 carbon monoxide Inorganic materials 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
229960002023 chloroprocaine Drugs 0.000 description 1
XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960001231 choline Drugs 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
239000000306 component Substances 0.000 description 1
229940125904 compound 1 Drugs 0.000 description 1
229940125797 compound 12 Drugs 0.000 description 1
229940126543 compound 14 Drugs 0.000 description 1
229940125758 compound 15 Drugs 0.000 description 1
229940126142 compound 16 Drugs 0.000 description 1
229940125782 compound 2 Drugs 0.000 description 1
229940125810 compound 20 Drugs 0.000 description 1
229940126086 compound 21 Drugs 0.000 description 1
229940126208 compound 22 Drugs 0.000 description 1
229940125833 compound 23 Drugs 0.000 description 1
229940125961 compound 24 Drugs 0.000 description 1
229940125846 compound 25 Drugs 0.000 description 1
229940125851 compound 27 Drugs 0.000 description 1
229940127204 compound 29 Drugs 0.000 description 1
229940126214 compound 3 Drugs 0.000 description 1
229940125877 compound 31 Drugs 0.000 description 1
229940125878 compound 36 Drugs 0.000 description 1
229940125807 compound 37 Drugs 0.000 description 1
229940127573 compound 38 Drugs 0.000 description 1
229940126540 compound 41 Drugs 0.000 description 1
229940125936 compound 42 Drugs 0.000 description 1
229940125844 compound 46 Drugs 0.000 description 1
229940127271 compound 49 Drugs 0.000 description 1
229940125898 compound 5 Drugs 0.000 description 1
229940125900 compound 59 Drugs 0.000 description 1
229940126179 compound 72 Drugs 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
235000008504 concentrate Nutrition 0.000 description 1
KUNSUQLRTQLHQQ-UHFFFAOYSA-N copper tin Chemical compound [Cu].[Sn] KUNSUQLRTQLHQQ-UHFFFAOYSA-N 0.000 description 1
NWFNSTOSIVLCJA-UHFFFAOYSA-L copper;diacetate;hydrate Chemical compound O.[Cu+2].CC([O-])=O.CC([O-])=O NWFNSTOSIVLCJA-UHFFFAOYSA-L 0.000 description 1
229940076286 cupric acetate Drugs 0.000 description 1
150000004292 cyclic ethers Chemical class 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000006317 cyclopropyl amino group Chemical group 0.000 description 1
231100000433 cytotoxic Toxicity 0.000 description 1
230000001472 cytotoxic effect Effects 0.000 description 1
238000013461 design Methods 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
PBGGNZZGJIKBMJ-UHFFFAOYSA-N di(propan-2-yl)azanide Chemical compound CC(C)[N-]C(C)C PBGGNZZGJIKBMJ-UHFFFAOYSA-N 0.000 description 1
KBNFODAYMUWUDO-UHFFFAOYSA-N diazonio-[1-(3-fluoro-1-phenylmethoxycarbonylpyrrolidin-3-yl)ethyl]azanide Chemical compound C1C(C(N=[N+]=[N-])C)(F)CCN1C(=O)OCC1=CC=CC=C1 KBNFODAYMUWUDO-UHFFFAOYSA-N 0.000 description 1
238000006193 diazotization reaction Methods 0.000 description 1
150000001991 dicarboxylic acids Chemical class 0.000 description 1
PMPYSSMGWFNAAQ-UHFFFAOYSA-N dichloromethane;n,n-diethylethanamine Chemical compound ClCCl.CCN(CC)CC PMPYSSMGWFNAAQ-UHFFFAOYSA-N 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
229940043237 diethanolamine Drugs 0.000 description 1
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
229910001873 dinitrogen Inorganic materials 0.000 description 1
XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
235000011180 diphosphates Nutrition 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
229910000397 disodium phosphate Inorganic materials 0.000 description 1
235000019800 disodium phosphate Nutrition 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000002934 diuretic Substances 0.000 description 1
230000001882 diuretic effect Effects 0.000 description 1
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000012039 electrophile Substances 0.000 description 1
239000003480 eluent Substances 0.000 description 1
238000010828 elution Methods 0.000 description 1
BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
238000010931 ester hydrolysis Methods 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
229940052303 ethers for general anesthesia Drugs 0.000 description 1
AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
GDZPWQCQDBQIJJ-UHFFFAOYSA-N ethyl 1-benzyl-4-methylpyrrolidine-3-carboxylate Chemical compound C1C(C)C(C(=O)OCC)CN1CC1=CC=CC=C1 GDZPWQCQDBQIJJ-UHFFFAOYSA-N 0.000 description 1
AEWXAXFFVMNSMX-UHFFFAOYSA-N ethyl 2-(cyclopropylamino)-3,5-difluorobenzoate Chemical compound C(C)OC(C1=C(C(=CC(=C1)F)F)NC1CC1)=O AEWXAXFFVMNSMX-UHFFFAOYSA-N 0.000 description 1
NSABSAJYHZYYMK-ZDUSSCGKSA-N ethyl 2-(cyclopropylamino)-3,6-difluoro-4-[(3s)-3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound FC1=C(NC2CC2)C(C(=O)OCC)=C(F)C=C1N1CC[C@H](NC(=O)OC(C)(C)C)C1 NSABSAJYHZYYMK-ZDUSSCGKSA-N 0.000 description 1
YZJZNNNOCHXFNJ-UHFFFAOYSA-N ethyl 2-(cyclopropylamino)-3,6-difluorobenzoate Chemical compound C(C)OC(C1=C(C(=CC=C1F)F)NC1CC1)=O YZJZNNNOCHXFNJ-UHFFFAOYSA-N 0.000 description 1
XGPFLQOBZSEQFM-UHFFFAOYSA-N ethyl 2-(cyclopropylamino)-3-fluorobenzoate Chemical compound C(C)OC(C1=C(C(=CC=C1)F)NC1CC1)=O XGPFLQOBZSEQFM-UHFFFAOYSA-N 0.000 description 1
KLDDQZNIRQUHKU-UHFFFAOYSA-N ethyl 2-(cyclopropylamino)-5-fluoro-4-pyrrolidin-1-ylbenzoate Chemical compound CCOC(=O)C1=CC(F)=C(N2CCCC2)C=C1NC1CC1 KLDDQZNIRQUHKU-UHFFFAOYSA-N 0.000 description 1
MYSSYHAITZSBEY-UHFFFAOYSA-N ethyl 2-(cyclopropylamino)-5-fluoro-6-methylsulfanylpyridine-3-carboxylate Chemical compound CCOC(=O)C1=CC(F)=C(SC)N=C1NC1CC1 MYSSYHAITZSBEY-UHFFFAOYSA-N 0.000 description 1
KOWLMUHLYWGECF-UHFFFAOYSA-N ethyl 2-chloro-5-fluoro-6-methylsulfanylpyridine-3-carboxylate Chemical compound CCOC(=O)C1=CC(F)=C(SC)N=C1Cl KOWLMUHLYWGECF-UHFFFAOYSA-N 0.000 description 1
CINXGNHRKLMYRK-UHFFFAOYSA-N ethyl 2-cyclopropylideneacetate Chemical compound CCOC(=O)C=C1CC1 CINXGNHRKLMYRK-UHFFFAOYSA-N 0.000 description 1
GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 description 1
XITYZNUXHDHZKA-JTQLQIEISA-N ethyl 3-chloro-2,5-difluoro-4-[(3s)-3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound ClC1=C(F)C(C(=O)OCC)=CC(F)=C1N1C[C@@H](NC(=O)OC(C)(C)C)CC1 XITYZNUXHDHZKA-JTQLQIEISA-N 0.000 description 1
KDKBIFLYOSNINK-ZDUSSCGKSA-N ethyl 3-chloro-2-(cyclopropylamino)-5-fluoro-4-[(3s)-3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound ClC1=C(NC2CC2)C(C(=O)OCC)=CC(F)=C1N1CC[C@H](NC(=O)OC(C)(C)C)C1 KDKBIFLYOSNINK-ZDUSSCGKSA-N 0.000 description 1
NXCURRNUONQADF-UHFFFAOYSA-N ethyl 3-ethoxy-2,5-difluoro-4-[3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound CCOC1=C(F)C(C(=O)OCC)=CC(F)=C1N1CC(NC(=O)OC(C)(C)C)CC1 NXCURRNUONQADF-UHFFFAOYSA-N 0.000 description 1
UFUOHMISUZIHNY-UHFFFAOYSA-N ethyl 3-ethoxy-2,5-difluorobenzoate Chemical compound CCOC(=O)C1=CC(F)=CC(OCC)=C1F UFUOHMISUZIHNY-UHFFFAOYSA-N 0.000 description 1
239000002024 ethyl acetate extract Substances 0.000 description 1
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
229940117927 ethylene oxide Drugs 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
239000011152 fibreglass Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
125000006419 fluorocyclopropyl group Chemical group 0.000 description 1
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
101150059798 grlA gene Proteins 0.000 description 1
101150097244 grxC2 gene Proteins 0.000 description 1
JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
101150070420 gyrA gene Proteins 0.000 description 1
230000002140 halogenating effect Effects 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
125000004464 hydroxyphenyl group Chemical group 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000000099 in vitro assay Methods 0.000 description 1
238000005462 in vivo assay Methods 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
230000003993 interaction Effects 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
VLODBNNWEWTQJX-UHFFFAOYSA-N iodocyclopropane Chemical compound IC1CC1 VLODBNNWEWTQJX-UHFFFAOYSA-N 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
150000003854 isothiazoles Chemical class 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 1
239000012160 loading buffer Substances 0.000 description 1
GPSDUZXPYCFOSQ-UHFFFAOYSA-N m-toluenecarboxylic acid Natural products CC1=CC=CC(C(O)=O)=C1 GPSDUZXPYCFOSQ-UHFFFAOYSA-N 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
108010093708 mamba intestinal toxin 1 Proteins 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
239000000155 melt Substances 0.000 description 1
SHOJXDKTYKFBRD-UHFFFAOYSA-N mesityl oxide Natural products CC(C)=CC(C)=O SHOJXDKTYKFBRD-UHFFFAOYSA-N 0.000 description 1
125000005341 metaphosphate group Chemical group 0.000 description 1
USJUUYYGHABIBU-UHFFFAOYSA-N methanesulfonamide;hydrochloride Chemical compound Cl.CS(N)(=O)=O USJUUYYGHABIBU-UHFFFAOYSA-N 0.000 description 1
QHRBNLHIYYHJNU-UHFFFAOYSA-N methyl 1,2,3,4-tetrahydroquinoline-8-carboxylate Chemical compound C1CCNC2=C1C=CC=C2C(=O)OC QHRBNLHIYYHJNU-UHFFFAOYSA-N 0.000 description 1
FLKMOQAAIRZPTP-UHFFFAOYSA-N methyl 5,6-difluoro-2-methylquinoline-8-carboxylate Chemical compound C1=C(C)N=C2C(C(=O)OC)=CC(F)=C(F)C2=C1 FLKMOQAAIRZPTP-UHFFFAOYSA-N 0.000 description 1
229940095102 methyl benzoate Drugs 0.000 description 1
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
238000005497 microtitration Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
PWBJWDKDPAPGED-UHFFFAOYSA-N n'-chlorobutanediamide Chemical compound NC(=O)CCC(=O)NCl PWBJWDKDPAPGED-UHFFFAOYSA-N 0.000 description 1
WHQSYGRFZMUQGQ-UHFFFAOYSA-N n,n-dimethylformamide;hydrate Chemical compound O.CN(C)C=O WHQSYGRFZMUQGQ-UHFFFAOYSA-N 0.000 description 1
QWAPDZOXNZQTRF-UHFFFAOYSA-N n-(cyclopropylcarbamoyl)-3-ethyl-2,4,5-trifluorobenzamide Chemical compound CCC1=C(F)C(F)=CC(C(=O)NC(=O)NC2CC2)=C1F QWAPDZOXNZQTRF-UHFFFAOYSA-N 0.000 description 1
VBBUFMFZDHLELS-UHFFFAOYSA-N n-(oxomethylidene)carbamoyl chloride Chemical compound ClC(=O)N=C=O VBBUFMFZDHLELS-UHFFFAOYSA-N 0.000 description 1
YXLVSYUUZGMLFZ-UHFFFAOYSA-N n-[1-(1-benzyl-4-methylpyrrolidin-3-yl)ethylidene]hydroxylamine Chemical compound C1C(C(C)=NO)C(C)CN1CC1=CC=CC=C1 YXLVSYUUZGMLFZ-UHFFFAOYSA-N 0.000 description 1
YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
NGZYRKGJWYJGRS-UHFFFAOYSA-N n-methylpyrrolidin-3-amine Chemical compound CNC1CCNC1 NGZYRKGJWYJGRS-UHFFFAOYSA-N 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
HGAWACRPWVRCFI-UHFFFAOYSA-N n-pyrrolidin-3-ylidenehydroxylamine Chemical compound ON=C1CCNC1 HGAWACRPWVRCFI-UHFFFAOYSA-N 0.000 description 1
XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
235000021096 natural sweeteners Nutrition 0.000 description 1
IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
BVOCPVIXARZNQN-UHFFFAOYSA-N nipecotamide Chemical compound NC(=O)C1CCCNC1 BVOCPVIXARZNQN-UHFFFAOYSA-N 0.000 description 1
XJLSEXAGTJCILF-UHFFFAOYSA-N nipecotic acid Chemical compound OC(=O)C1CCCNC1 XJLSEXAGTJCILF-UHFFFAOYSA-N 0.000 description 1
HYDZPXNVHXJHBG-UHFFFAOYSA-N o-benzylhydroxylamine;hydron;chloride Chemical compound Cl.NOCC1=CC=CC=C1 HYDZPXNVHXJHBG-UHFFFAOYSA-N 0.000 description 1
WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
125000003431 oxalo group Chemical group 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
101150110811 parC gene Proteins 0.000 description 1
WYMSBXTXOHUIGT-UHFFFAOYSA-N paraoxon Chemical compound CCOP(=O)(OCC)OC1=CC=C([N+]([O-])=O)C=C1 WYMSBXTXOHUIGT-UHFFFAOYSA-N 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
229940049953 phenylacetate Drugs 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
102000020233 phosphotransferase Human genes 0.000 description 1
XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
LTEKQAPRXFBRNN-UHFFFAOYSA-N piperidin-4-ylmethanamine Chemical compound NCC1CCNCC1 LTEKQAPRXFBRNN-UHFFFAOYSA-N 0.000 description 1
229960005235 piperonyl butoxide Drugs 0.000 description 1
239000013612 plasmid Substances 0.000 description 1
239000003880 polar aprotic solvent Substances 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
229920001155 polypropylene Polymers 0.000 description 1
230000008092 positive effect Effects 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
230000008569 process Effects 0.000 description 1
ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical group C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
125000004941 pyridazin-5-yl group Chemical group N1=NC=CC(=C1)* 0.000 description 1
BOYOFKUHNQBNPY-UHFFFAOYSA-N pyridine-2-carboxylic acid;hydrofluoride Chemical compound F.OC(=O)C1=CC=CC=N1 BOYOFKUHNQBNPY-UHFFFAOYSA-N 0.000 description 1
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
QGKLPGKXAVVPOJ-UHFFFAOYSA-N pyrrolidin-3-one Chemical compound O=C1CCNC1 QGKLPGKXAVVPOJ-UHFFFAOYSA-N 0.000 description 1
XSUHSSTUTHPGDQ-UHFFFAOYSA-N pyrrolidin-3-ylmethylcarbamic acid Chemical compound OC(=O)NCC1CCNC1 XSUHSSTUTHPGDQ-UHFFFAOYSA-N 0.000 description 1
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
229920003987 resole Polymers 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
102220012991 rs111033344 Human genes 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
229940116351 sebacate Drugs 0.000 description 1
CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
BHRZNVHARXXAHW-UHFFFAOYSA-N sec-butylamine Chemical compound CCC(C)N BHRZNVHARXXAHW-UHFFFAOYSA-N 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
150000003385 sodium Chemical class 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
KSAVQLQVUXSOCR-UHFFFAOYSA-N sodium;2-[dodecanoyl(methyl)amino]acetic acid Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC(O)=O KSAVQLQVUXSOCR-UHFFFAOYSA-N 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
229940063673 spermidine Drugs 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
229910000080 stannane Inorganic materials 0.000 description 1
FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000009897 systematic effect Effects 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000007916 tablet composition Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
LRTPRHCNWAEZBN-UWVGGRQHSA-N tert-butyl (3as,7ar)-1,2,3,3a,4,6,7,7a-octahydropyrrolo[3,4-c]pyridine-5-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@H]2CNC[C@H]21 LRTPRHCNWAEZBN-UWVGGRQHSA-N 0.000 description 1
LGEWGFOMLJQHLL-UHFFFAOYSA-N tert-butyl 2,3,4,4a,5,6,7,7a-octahydropyrrolo[3,4-b]pyridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC2CNCC12 LGEWGFOMLJQHLL-UHFFFAOYSA-N 0.000 description 1
IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 1
MFPSKADFMNXZIY-UHFFFAOYSA-N tert-butyl n-(2,7-diazaspiro[4.4]nonan-2-yl)carbamate Chemical compound C1N(NC(=O)OC(C)(C)C)CCC11CNCC1 MFPSKADFMNXZIY-UHFFFAOYSA-N 0.000 description 1
OWGYHEOEGOLPEK-UHFFFAOYSA-N tert-butyl n-(2-pyrrolidin-3-ylethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCC1CCNC1 OWGYHEOEGOLPEK-UHFFFAOYSA-N 0.000 description 1
DIQWSFWWYVRXRO-UHFFFAOYSA-N tert-butyl n-(3-methylpyrrolidin-3-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1(C)CCNC1 DIQWSFWWYVRXRO-UHFFFAOYSA-N 0.000 description 1
BKITXDSDJGOXPN-UHFFFAOYSA-N tert-butyl n-(4-methylpyrrolidin-3-yl)carbamate Chemical compound CC1CNCC1NC(=O)OC(C)(C)C BKITXDSDJGOXPN-UHFFFAOYSA-N 0.000 description 1
CGEBPOMWRHSMLI-UHFFFAOYSA-N tert-butyl n-(5-azaspiro[2.4]heptan-7-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CNCC11CC1 CGEBPOMWRHSMLI-UHFFFAOYSA-N 0.000 description 1
WIEJVMZWPIUWHO-UHFFFAOYSA-N tert-butyl n-(pyrrolidin-3-ylmethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC1CCNC1 WIEJVMZWPIUWHO-UHFFFAOYSA-N 0.000 description 1
HKMRTYHBVMXVTE-UHFFFAOYSA-N tert-butyl n-[(1,3-dibenzylpyrrolidin-3-yl)methyl]carbamate Chemical compound C1CN(CC=2C=CC=CC=2)CC1(CNC(=O)OC(C)(C)C)CC1=CC=CC=C1 HKMRTYHBVMXVTE-UHFFFAOYSA-N 0.000 description 1
XUQHCLUBVDHVEK-UHFFFAOYSA-N tert-butyl n-[(1-benzyl-3-hydroxypyrrolidin-3-yl)methyl]carbamate Chemical compound C1C(CNC(=O)OC(C)(C)C)(O)CCN1CC1=CC=CC=C1 XUQHCLUBVDHVEK-UHFFFAOYSA-N 0.000 description 1
ZVQYLSQGHKZRPJ-UHFFFAOYSA-N tert-butyl n-[(1-benzyl-3-phenylpyrrolidin-3-yl)methyl]carbamate Chemical compound C1C(CNC(=O)OC(C)(C)C)(C=2C=CC=CC=2)CCN1CC1=CC=CC=C1 ZVQYLSQGHKZRPJ-UHFFFAOYSA-N 0.000 description 1
HJUZGKGDCUOVML-DTWKUNHWSA-N tert-butyl n-[(1s)-1-[(3r)-pyrrolidin-3-yl]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](C)[C@@H]1CCNC1 HJUZGKGDCUOVML-DTWKUNHWSA-N 0.000 description 1
ICTZIUAWAKFRDZ-AGBAINOHSA-N tert-butyl n-[(2r)-2-[3-(dibenzylamino)-1-ethyl-6-fluoro-2,4-dioxoquinazolin-7-yl]-2-pyrrolidin-3-ylpropyl]carbamate Chemical compound O=C1N(CC)C2=CC([C@](C)(CNC(=O)OC(C)(C)C)C3CNCC3)=C(F)C=C2C(=O)N1N(CC=1C=CC=CC=1)CC1=CC=CC=C1 ICTZIUAWAKFRDZ-AGBAINOHSA-N 0.000 description 1
VRLMNTJDNRPIFB-UHFFFAOYSA-N tert-butyl n-[(3-benzylpyrrolidin-3-yl)methyl]carbamate Chemical compound C=1C=CC=CC=1CC1(CNC(=O)OC(C)(C)C)CCNC1 VRLMNTJDNRPIFB-UHFFFAOYSA-N 0.000 description 1
CEFJWUXTHLISAP-UHFFFAOYSA-N tert-butyl n-[(4-methylpyrrolidin-3-yl)methyl]carbamate Chemical compound CC1CNCC1CNC(=O)OC(C)(C)C CEFJWUXTHLISAP-UHFFFAOYSA-N 0.000 description 1
QALVWAHCRSYNFG-UHFFFAOYSA-N tert-butyl n-[1-(1-benzyl-4-methylpyrrolidin-3-yl)ethyl]carbamate Chemical compound C1C(C)C(C(NC(=O)OC(C)(C)C)C)CN1CC1=CC=CC=C1 QALVWAHCRSYNFG-UHFFFAOYSA-N 0.000 description 1
LZUVJGDBPICSGK-UHFFFAOYSA-N tert-butyl n-[1-[1-(3-amino-1-cyclopropyl-6-fluoro-8-methyl-2,4-dioxoquinazolin-7-yl)-3-methoxypyrrolidin-3-yl]ethyl]carbamate Chemical compound C1C(OC)(C(C)NC(=O)OC(C)(C)C)CCN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C LZUVJGDBPICSGK-UHFFFAOYSA-N 0.000 description 1
CQTSDJNUHOTZNB-UHFFFAOYSA-N tert-butyl n-[1-[1-cyclopropyl-8-fluoro-6-methoxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-2,4-dioxoquinazolin-7-yl]pyrrolidin-3-yl]carbamate Chemical compound COC1=CC(C(N(NC(=O)OC(C)(C)C)C(=O)N2C3CC3)=O)=C2C(F)=C1N1CCC(NC(=O)OC(C)(C)C)C1 CQTSDJNUHOTZNB-UHFFFAOYSA-N 0.000 description 1
MNIHYAVDKLMINM-VIFPVBQESA-N tert-butyl n-[2-[(3s)-pyrrolidin-3-yl]propan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)NC(C)(C)[C@H]1CCNC1 MNIHYAVDKLMINM-VIFPVBQESA-N 0.000 description 1
ASHQLXVHLDPBBB-UHFFFAOYSA-N tert-butyl n-[7a-(aminomethyl)-3,3a,4,5,6,7-hexahydro-1h-isoindol-2-yl]carbamate Chemical compound C1CCCC2(CN)CN(NC(=O)OC(C)(C)C)CC21 ASHQLXVHLDPBBB-UHFFFAOYSA-N 0.000 description 1
JJOOCVNFHZXGPL-UHFFFAOYSA-N tert-butyl n-amino-n-benzoylcarbamate Chemical compound CC(C)(C)OC(=O)N(N)C(=O)C1=CC=CC=C1 JJOOCVNFHZXGPL-UHFFFAOYSA-N 0.000 description 1
JHLVEBNWCCKSGY-UHFFFAOYSA-N tert-butyl n-methylcarbamate Chemical compound CNC(=O)OC(C)(C)C JHLVEBNWCCKSGY-UHFFFAOYSA-N 0.000 description 1
IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical group CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 1
238000012360 testing method Methods 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
150000003557 thiazoles Chemical class 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
150000007970 thio esters Chemical class 0.000 description 1
125000005309 thioalkoxy group Chemical group 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
ZFDIRQKJPRINOQ-UHFFFAOYSA-N transbutenic acid ethyl ester Natural products CCOC(=O)C=CC ZFDIRQKJPRINOQ-UHFFFAOYSA-N 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
230000007704 transition Effects 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
125000004953 trihalomethyl group Chemical group 0.000 description 1
PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
- C07D239/96—Two oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Animal Behavior & Ethology (AREA)
Communicable Diseases (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Virology (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Oncology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Molecular Biology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
Paper (AREA)

OA1200200210A 2000-01-24 2000-12-12 3-Aminoquinazolin-2,4-dione antibacterial agents. OA12316A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US17825200P	2000-01-24	2000-01-24
US24126700P	2000-10-18	2000-10-18

Publications (1)

Publication Number	Publication Date
OA12316A true OA12316A (en)	2006-05-15

Family

ID=26874138

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA1200200210A OA12316A (en)	2000-01-24	2000-12-12	3-Aminoquinazolin-2,4-dione antibacterial agents.

Country Status (38)

Country	Link
US (2)	US7094780B1 (pl)
EP (1)	EP1255739B1 (pl)
JP (1)	JP4811978B2 (pl)
KR (1)	KR20020067701A (pl)
CN (1)	CN1425008A (pl)
AP (1)	AP2002002603A0 (pl)
AR (1)	AR030186A1 (pl)
AT (1)	ATE398110T1 (pl)
AU (1)	AU783078B2 (pl)
BG (1)	BG107023A (pl)
BR (1)	BR0017010A (pl)
CA (1)	CA2393802C (pl)
CO (1)	CO5320600A1 (pl)
CR (1)	CR6709A (pl)
DE (1)	DE60039194D1 (pl)
EA (1)	EA005585B1 (pl)
EE (1)	EE200200412A (pl)
ES (1)	ES2304992T3 (pl)
GE (1)	GEP20053429B (pl)
HK (1)	HK1054237A1 (pl)
HN (1)	HN2001000009A (pl)
HR (1)	HRP20020696A2 (pl)
HU (1)	HUP0204101A3 (pl)
IL (1)	IL150393A0 (pl)
IS (1)	IS6448A (pl)
MA (1)	MA26866A1 (pl)
MX (1)	MXPA02005989A (pl)
NO (1)	NO20023516D0 (pl)
OA (1)	OA12316A (pl)
PA (1)	PA8510101A1 (pl)
PE (1)	PE20011060A1 (pl)
PL (1)	PL356837A1 (pl)
SK (1)	SK10572002A3 (pl)
SV (1)	SV2001000288A (pl)
TN (1)	TNSN01011A1 (pl)
UY (1)	UY26551A1 (pl)
WO (1)	WO2001053273A1 (pl)
YU (1)	YU55902A (pl)

Families Citing this family (46)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SK286420B6 (sk)	1997-09-15	2008-09-05	The Procter & Gamble Company	Zlúčenina so štruktúrou chinolónu, farmaceutický prostriedok s jej obsahom a jej použitie
JP2004532876A (ja)	2001-05-30	2004-10-28	ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー	抗菌剤
EP1401830A2 (en) *	2001-06-19	2004-03-31	Warner-Lambert Company LLC	Quinazolinediones as antibacterial agents
US6900224B2 (en) *	2002-07-31	2005-05-31	The Procter & Gamble Company	Antimicrobial quinolones, their compositions and uses
WO2005026153A1 (en) *	2003-09-12	2005-03-24	Warner-Lambert Company Llc	Quinazoline-2, 4-diones as antibacterial agents
JP2007505096A (ja) *	2003-09-12	2007-03-08	ワーナー−ランバートカンパニーリミティドライアビリティーカンパニー	キノロン抗菌剤
EP1687296A1 (en) *	2003-11-18	2006-08-09	Warner-Lambert Company LLC	Antibacterial aminoquinazolidinedione derivatives
WO2006019965A2 (en) *	2004-07-16	2006-02-23	Takeda San Diego, Inc.	Dipeptidyl peptidase inhibitors
GB0416730D0 (en)	2004-07-27	2004-09-01	Novartis Ag	Organic compounds
ATE447572T1 (de) *	2005-01-26	2009-11-15	Hoffmann La Roche	Phenylmethanonderivate und ihre verwendung als glycin-transporter-1-hemmer
GB0507298D0 (en)	2005-04-11	2005-05-18	Novartis Ag	Organic compounds
US7977346B2 (en)	2006-01-17	2011-07-12	Guoqing Paul Chen	Spiro compounds and methods of use
MX2008012488A (es)	2006-03-28	2008-10-10	Procter & Gamble	Un proceso de acoplamiento para preparar intermedios de quinolona.
EP2001862B1 (en)	2006-03-28	2011-04-27	Warner Chilcott Company, LLC	Malate salts, and polymorphs of (3s,5s)-7-[3-amino-5-methyl-piperidinyl]-1-cyclopropyl-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid
US20080139574A1 (en)	2006-11-30	2008-06-12	Cadila Healthcare Limited	Novel quinoline derivatives
PT2239257E (pt) *	2008-01-30	2012-09-12	Shin Poong Pharmaceutical Co Ltd	Novo derivado de quinazolina-2,4-diona e composições médicas para a profilaxia e tratamento da doença dos nervos cranianos contendo o dito derivado
WO2011031745A1 (en)	2009-09-09	2011-03-17	Achaogen, Inc.	Antibacterial fluoroquinolone analogs
US8754114B2 (en)	2010-12-22	2014-06-17	Incyte Corporation	Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3
EP2686320B1 (en)	2011-03-15	2016-05-18	Merck Sharp & Dohme Corp.	Tricyclic gyrase inhibitors
PT2796460T (pt) *	2011-12-21	2018-11-05	Shanghai hengrui pharmaceutical co ltd	Derivado pirrole de anel heteroarilo de seis membros, método de preparação do mesmo e suas utilizações médicas
RS58514B1 (sr)	2012-06-13	2019-04-30	Incyte Holdings Corp	Supstituisana triciklična jedinjenja kao inhibitori fgfr
US9388185B2 (en)	2012-08-10	2016-07-12	Incyte Holdings Corporation	Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors
CN105189505B (zh)	2012-09-12	2019-03-22	默克夏普&多梅有限公司	用作抗菌剂的三环促旋酶抑制剂
US9266892B2 (en)	2012-12-19	2016-02-23	Incyte Holdings Corporation	Fused pyrazoles as FGFR inhibitors
PH12015502383B1 (en)	2013-04-19	2023-02-03	Incyte Holdings Corp	Bicyclic heterocycles as fgfr inhibitors
US10851105B2 (en)	2014-10-22	2020-12-01	Incyte Corporation	Bicyclic heterocycles as FGFR4 inhibitors
TWI712601B (zh)	2015-02-20	2020-12-11	美商英塞特公司	作為fgfr抑制劑之雙環雜環
US9580423B2 (en)	2015-02-20	2017-02-28	Incyte Corporation	Bicyclic heterocycles as FGFR4 inhibitors
MA41551A (fr)	2015-02-20	2017-12-26	Incyte Corp	Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4
CN108530448A (zh) *	2017-03-02	2018-09-14	浙江司太立制药股份有限公司	含有碱性氮杂螺环片段的苯并噻嗪-4-酮类化合物及其制备方法
AR111960A1 (es)	2017-05-26	2019-09-04	Incyte Corp	Formas cristalinas de un inhibidor de fgfr y procesos para su preparación
HRP20241288T1 (hr)	2018-05-04	2024-12-06	Incyte Corporation	Čvrsti oblici fgfr inhibitora i postupci za njihovu proizvodnju
AU2019262579B2 (en)	2018-05-04	2024-09-12	Incyte Corporation	Salts of an FGFR inhibitor
CN111620866A (zh) *	2019-02-27	2020-09-04	南京药石科技股份有限公司	一种顺式-7,7-二氟-六氢-1H 吡咯并[3,4-c]吡啶衍生物及其制备方法
US11628162B2 (en)	2019-03-08	2023-04-18	Incyte Corporation	Methods of treating cancer with an FGFR inhibitor
US11591329B2 (en)	2019-07-09	2023-02-28	Incyte Corporation	Bicyclic heterocycles as FGFR inhibitors
WO2021067374A1 (en)	2019-10-01	2021-04-08	Incyte Corporation	Bicyclic heterocycles as fgfr inhibitors
CA3157361A1 (en)	2019-10-14	2021-04-22	Incyte Corporation	Bicyclic heterocycles as fgfr inhibitors
WO2021076728A1 (en)	2019-10-16	2021-04-22	Incyte Corporation	Bicyclic heterocycles as fgfr inhibitors
JP7832891B2 (ja)	2019-12-04	2026-03-18	インサイト・コーポレイション	Ｆｇｆｒ阻害剤の誘導体
CA3163875A1 (en)	2019-12-04	2021-06-10	Incyte Corporation	Tricyclic heterocycles as fgfr inhibitors
US12012409B2 (en)	2020-01-15	2024-06-18	Incyte Corporation	Bicyclic heterocycles as FGFR inhibitors
CN111499513B (zh) *	2020-04-24	2023-03-14	上海毕得医药科技股份有限公司	一种2,3,4,5-四溴苯甲酸酯的合成方法
WO2022221170A1 (en)	2021-04-12	2022-10-20	Incyte Corporation	Combination therapy comprising an fgfr inhibitor and a nectin-4 targeting agent
US11939331B2 (en)	2021-06-09	2024-03-26	Incyte Corporation	Tricyclic heterocycles as FGFR inhibitors
CA3220155A1 (en)	2021-06-09	2022-12-15	Incyte Corporation	Tricyclic heterocycles as fgfr inhibitors

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE1068263B (pl) *		1959-11-05
FR1203542A (fr) *	1958-02-25	1960-01-19	Rhone Poulenc Sa	Nouveaux dérivés de la phénothiazine comportant en position 10 une chaîne pipérazinique et leurs procédés de préparation
EP0035619B1 (fr)	1980-03-10	1984-07-25	BERRI-BALZAC Société dite:	Dérivés d'amino-3 (1H,3H) quinazolinedione-2,4
GB2097784A (en)	1981-04-28	1982-11-10	Davidson Dr John Stirton	Dihydrobenzotriazepine diones; aminoquinazoline diones
WO1994014809A1 (de)	1992-12-23	1994-07-07	Byk Gulden Lomberg Chemische Fabrik Gmbh	Anellierte uracilderivate
WO1998018781A2 (en)	1996-10-28	1998-05-07	Versicor, Inc.	Fused 2,4-pyrimidinedione combinatorial libraries, their preparation and the use of fused 2,4-pyrimidinediones derivatives as antimicrobial agents
DK1028950T3 (da) *	1997-10-28	2003-09-01	Warner Lambert Co	7-substituerede quinazolin-2,4-dioner nyttige som antibakterielle midler
TR200003429T2 (tr)	1998-05-26	2001-07-23	Warner-Lambert Company	Hücresel çoğalma inhibitörleri olarak bisiklik pirimidinler ve bisiklik 3,4-dihidropirimidinler.
AU765729B2 (en) *	1998-12-11	2003-09-25	F. Hoffmann-La Roche Ag	Cyclic hydrazine derivatives as TNF-alpha inhibitors

2000
- 2000-12-12 SK SK1057-2002A patent/SK10572002A3/sk unknown
- 2000-12-12 DE DE60039194T patent/DE60039194D1/de not_active Expired - Lifetime
- 2000-12-12 GE GE4912A patent/GEP20053429B/en unknown
- 2000-12-12 IL IL15039300A patent/IL150393A0/xx unknown
- 2000-12-12 HK HK03106519.6A patent/HK1054237A1/zh unknown
- 2000-12-12 JP JP2001553275A patent/JP4811978B2/ja not_active Expired - Fee Related
- 2000-12-12 YU YU55902A patent/YU55902A/sh unknown
- 2000-12-12 MX MXPA02005989A patent/MXPA02005989A/es active IP Right Grant
- 2000-12-12 WO PCT/US2000/033656 patent/WO2001053273A1/en not_active Ceased
- 2000-12-12 ES ES00984246T patent/ES2304992T3/es not_active Expired - Lifetime
- 2000-12-12 HR HR20020696A patent/HRP20020696A2/hr not_active Application Discontinuation
- 2000-12-12 US US10/182,221 patent/US7094780B1/en not_active Expired - Fee Related
- 2000-12-12 EA EA200200661A patent/EA005585B1/ru not_active IP Right Cessation
- 2000-12-12 AU AU20899/01A patent/AU783078B2/en not_active Ceased
- 2000-12-12 KR KR1020027009515A patent/KR20020067701A/ko not_active Withdrawn
- 2000-12-12 CA CA2393802A patent/CA2393802C/en not_active Expired - Fee Related
- 2000-12-12 AP APAP/P/2002/002603A patent/AP2002002603A0/en unknown
- 2000-12-12 EE EEP200200412A patent/EE200200412A/xx unknown
- 2000-12-12 OA OA1200200210A patent/OA12316A/en unknown
- 2000-12-12 HU HU0204101A patent/HUP0204101A3/hu unknown
- 2000-12-12 BR BR0017010-0A patent/BR0017010A/pt not_active Application Discontinuation
- 2000-12-12 EP EP00984246A patent/EP1255739B1/en not_active Expired - Lifetime
- 2000-12-12 PL PL00356837A patent/PL356837A1/pl not_active Application Discontinuation
- 2000-12-12 CN CN00818578A patent/CN1425008A/zh active Pending
- 2000-12-12 AT AT00984246T patent/ATE398110T1/de not_active IP Right Cessation
2001
- 2001-01-19 PA PA20018510101A patent/PA8510101A1/es unknown
- 2001-01-22 PE PE2001000066A patent/PE20011060A1/es not_active Application Discontinuation
- 2001-01-22 HN HN2001000009A patent/HN2001000009A/es unknown
- 2001-01-22 SV SV2001000288A patent/SV2001000288A/es not_active Application Discontinuation
- 2001-01-22 TN TNTNSN01011A patent/TNSN01011A1/en unknown
- 2001-01-22 CO CO01004183A patent/CO5320600A1/es not_active Application Discontinuation
- 2001-01-22 UY UY26551A patent/UY26551A1/es not_active Application Discontinuation
- 2001-01-23 AR ARP010100278A patent/AR030186A1/es unknown
2002
- 2002-06-27 IS IS6448A patent/IS6448A/is unknown
- 2002-07-19 CR CR6709A patent/CR6709A/es not_active Application Discontinuation
- 2002-07-22 MA MA26734A patent/MA26866A1/fr unknown
- 2002-07-23 NO NO20023516A patent/NO20023516D0/no not_active Application Discontinuation
- 2002-08-22 BG BG107023A patent/BG107023A/xx unknown
2006
- 2006-06-13 US US11/452,121 patent/US7582627B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
EP1255739A1 (en)	2002-11-13
HUP0204101A3 (en)	2004-05-28
YU55902A (sh)	2006-01-16
GEP20053429B (en)	2005-01-25
CO5320600A1 (es)	2003-09-30
JP2003520277A (ja)	2003-07-02
HK1054237A1 (zh)	2003-11-21
TNSN01011A1 (en)	2005-11-10
US20060183762A1 (en)	2006-08-17
MXPA02005989A (es)	2002-10-23
US7094780B1 (en)	2006-08-22
US20060287308A1 (en)	2006-12-21
HUP0204101A2 (hu)	2003-04-28
HRP20020696A2 (en)	2003-12-31
BR0017010A (pt)	2002-11-05
EP1255739B1 (en)	2008-06-11
MA26866A1 (fr)	2004-12-20
US7582627B2 (en)	2009-09-01
CN1425008A (zh)	2003-06-18
CR6709A (es)	2003-11-25
ATE398110T1 (de)	2008-07-15
WO2001053273A1 (en)	2001-07-26
NO20023516L (no)	2002-07-23
IL150393A0 (en)	2002-12-01
EE200200412A (et)	2003-10-15
AU2089901A (en)	2001-07-31
KR20020067701A (ko)	2002-08-23
CA2393802A1 (en)	2001-07-26
AR030186A1 (es)	2003-08-13
NO20023516D0 (no)	2002-07-23
HN2001000009A (es)	2001-06-13
JP4811978B2 (ja)	2011-11-09
CA2393802C (en)	2011-04-19
ES2304992T3 (es)	2008-11-01
AP2002002603A0 (en)	2002-09-30
PL356837A1 (pl)	2004-07-12
EA200200661A1 (ru)	2003-02-27
PA8510101A1 (es)	2003-06-30
BG107023A (en)	2003-04-30
PE20011060A1 (es)	2001-10-12
EA005585B1 (ru)	2005-04-28
AU783078B2 (en)	2005-09-22
UY26551A1 (es)	2001-04-30
IS6448A (is)	2002-06-27
SV2001000288A (es)	2001-11-30
SK10572002A3 (sk)	2003-10-07
DE60039194D1 (de)	2008-07-24

Publication	Publication Date	Title
OA12316A (en)	2006-05-15	3-Aminoquinazolin-2,4-dione antibacterial agents.
RS55902B1 (sr)	2017-09-29	Obujmica za crevo
JPH0819099B2 (ja)	1996-02-28	アザビシクロキノロンカルボン酸化合物製造用中間体
HU196986B (en)	1989-02-28	Process for producing new naphtiridine- and quinoline-carboxylic acids of antibacterial activity and pharmaceutical compositions containing them
EP1028950B1 (en)	2003-05-02	7-substituted quinazolin-2,4-diones useful as antibacterial agents
EP3080131A1 (en)	2016-10-19	Imidazopyridazine compounds useful as modulators of il-12, il-23 and/or ifn alpha responses
JP2003026574A (ja)	2003-01-29	抗バクテリア剤
NZ243214A (en)	1995-07-26	7-isoindolino-quinolone and naphthyridonecarboxylic acid derivatives and pharmaceutical compositions
AU748749B2 (en)	2002-06-13	Isoquinolones
CZ190393A3 (en)	1994-04-13	Derivatives of 7-isoindolinylquinoline and 7-isoindolinylnaphthhydridone
JPS61243077A (ja)	1986-10-29	抗菌剤
HU219581B (hu)	2001-05-28	Új piridon-karbonsav-származékok, eljárás előállításukra, ezeket tartalmazó gyógyszerkészítmények, valamint intermedierek
EP0362759A1 (en)	1990-04-11	Pyridonecarboxylic acids
US20030114666A1 (en)	2003-06-19	Antibacterial agents
WO1995021163A1 (en)	1995-08-10	Pyridonecarboxylic acid derivative substituted by bicyclic amino group, ester thereof, salt thereof, and bicyclic amine as intermediate therefor
EP0347851A1 (en)	1989-12-27	Quinolonecarboxylic acids
JPH037260A (ja)	1991-01-14	新規キノロン誘導体またはその塩及びこれを含有する抗菌剤
JP3951136B2 (ja)	2007-08-01	新規ピリドンカルボン酸誘導体又はその塩並びに該物質を有効成分とする抗菌剤
JP4009874B2 (ja)	2007-11-21	新規ピリドンカルボン酸誘導体又はその塩並びに該物質を有効成分とする抗菌剤
JPWO1996012704A1 (ja)	1997-11-25	新規ピリドンカルボン酸誘導体又はその塩並びに該物質を有効成分とする抗菌剤