SK4322003A3 - Aza- and polyaza-naphthalenyl carboxamides useful as HIV integrase inhibitors - Google Patents

Aza- and polyaza-naphthalenyl carboxamides useful as HIV integrase inhibitors Download PDF

Info

Publication number: SK4322003A3
Authority: SK; Slovakia
Prior art keywords: alkyl; fluoroalkyl; substituted; hydroxy; halogen
Prior art date: 2000-10-12

Application number

SK432-2003A

Other languages

English (en)

Slovak (sk)

Inventor

Neville J Anthony

Robert P Gomez

Steven D Young

Melissa Egbertson

John S Wai

Linghang Zhuang

Mark Embrey

Lekhanh Tran

Jeffrey Y Melamed

Marie H Langford

James P Guare

Thorsten E Fisher

Samson M Jolly

Michelle KUO

Debra S Perlow

Jennifer J Bennett

Timothy W Funk

Original Assignee

Merck & Co Inc

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.)

2000-10-12

Filing date

2001-10-09

Publication date

2003-09-11

2001-10-09 Application filed by Merck & Co Inc filed Critical Merck & Co Inc

2003-09-11 Publication of SK4322003A3 publication Critical patent/SK4322003A3/sk

Links

229940099797 HIV integrase inhibitor Drugs 0.000 title description 4
239000003084 hiv integrase inhibitor Substances 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims abstract description 118
208000030507 AIDS Diseases 0.000 claims abstract description 29
150000003839 salts Chemical class 0.000 claims abstract description 24
108010002459 HIV Integrase Proteins 0.000 claims abstract description 10
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
208000015181 infectious disease Diseases 0.000 claims abstract description 8
-1 phenyloxy Chemical group 0.000 claims description 109
150000002367 halogens Chemical class 0.000 claims description 52
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 48
229910052736 halogen Inorganic materials 0.000 claims description 47
229910052757 nitrogen Inorganic materials 0.000 claims description 45
125000001424 substituent group Chemical group 0.000 claims description 44
125000000217 alkyl group Chemical group 0.000 claims description 43
125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 36
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
125000000623 heterocyclic group Chemical group 0.000 claims description 22
229910052799 carbon Inorganic materials 0.000 claims description 20
125000003709 fluoroalkyl group Chemical group 0.000 claims description 17
125000005842 heteroatom Chemical group 0.000 claims description 17
229920006395 saturated elastomer Polymers 0.000 claims description 16
229910052717 sulfur Inorganic materials 0.000 claims description 16
229910052760 oxygen Inorganic materials 0.000 claims description 15
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
125000001309 chloro group Chemical group Cl* 0.000 claims description 10
125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 10
125000003118 aryl group Chemical group 0.000 claims description 9
125000001072 heteroaryl group Chemical group 0.000 claims description 9
239000011593 sulfur Chemical group 0.000 claims description 9
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
239000001301 oxygen Chemical group 0.000 claims description 8
125000004432 carbon atom Chemical group C* 0.000 claims description 7
125000005843 halogen group Chemical group 0.000 claims description 7
230000002401 inhibitory effect Effects 0.000 claims description 7
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 7
125000001624 naphthyl group Chemical group 0.000 claims description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
DIDKWCOCQJWMDJ-UHFFFAOYSA-N 5-(1,1-dioxothiazinan-2-yl)-n-[(4-fluorophenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound C12=CC=CN=C2C(O)=C(C(=O)NCC=2C=CC(F)=CC=2)N=C1N1CCCCS1(=O)=O DIDKWCOCQJWMDJ-UHFFFAOYSA-N 0.000 claims description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 4
150000001721 carbon Chemical group 0.000 claims description 4
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
125000003342 alkenyl group Chemical group 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
238000000034 method Methods 0.000 abstract description 39
239000003443 antiviral agent Substances 0.000 abstract description 11
230000010076 replication Effects 0.000 abstract description 9
239000003112 inhibitor Substances 0.000 abstract description 6
239000002955 immunomodulating agent Substances 0.000 abstract description 5
229940121354 immunomodulator Drugs 0.000 abstract description 5
239000004615 ingredient Substances 0.000 abstract description 5
229960005486 vaccine Drugs 0.000 abstract description 4
239000003242 anti bacterial agent Substances 0.000 abstract description 2
229940088710 antibiotic agent Drugs 0.000 abstract description 2
229940053202 antiepileptics carboxamide derivative Drugs 0.000 abstract description 2
230000002265 prevention Effects 0.000 abstract description 2
JKNBCQYLFYHBHU-UHFFFAOYSA-N 1,8-naphthyridine-2-carboxamide Chemical class C1=CC=NC2=NC(C(=O)N)=CC=C21 JKNBCQYLFYHBHU-UHFFFAOYSA-N 0.000 abstract 1
229940042443 other antivirals in atc Drugs 0.000 abstract 1
ZEXKKIXCRDTKBF-UHFFFAOYSA-N quinoline-2-carboxamide Chemical compound C1=CC=CC2=NC(C(=O)N)=CC=C21 ZEXKKIXCRDTKBF-UHFFFAOYSA-N 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
239000000203 mixture Substances 0.000 description 40
239000007787 solid Substances 0.000 description 37
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 36
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 35
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
239000000243 solution Substances 0.000 description 31
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
238000002360 preparation method Methods 0.000 description 29
239000011541 reaction mixture Substances 0.000 description 29
238000005481 NMR spectroscopy Methods 0.000 description 24
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 22
241000725303 Human immunodeficiency virus Species 0.000 description 22
238000006243 chemical reaction Methods 0.000 description 22
238000004128 high performance liquid chromatography Methods 0.000 description 22
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 20
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 19
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
239000000047 product Substances 0.000 description 17
239000002904 solvent Substances 0.000 description 17
239000000839 emulsion Substances 0.000 description 16
235000019439 ethyl acetate Nutrition 0.000 description 15
238000010265 fast atom bombardment Methods 0.000 description 14
229910052739 hydrogen Inorganic materials 0.000 description 13
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
208000031886 HIV Infections Diseases 0.000 description 11
102100034343 Integrase Human genes 0.000 description 11
238000010992 reflux Methods 0.000 description 11
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
208000037357 HIV infectious disease Diseases 0.000 description 10
108010061833 Integrases Proteins 0.000 description 10
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
239000011734 sodium Substances 0.000 description 10
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 9
230000015572 biosynthetic process Effects 0.000 description 9
239000012074 organic phase Substances 0.000 description 9
239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 9
108020004414 DNA Proteins 0.000 description 8
108010078851 HIV Reverse Transcriptase Proteins 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
150000001412 amines Chemical class 0.000 description 8
238000003556 assay Methods 0.000 description 8
239000000460 chlorine Substances 0.000 description 8
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 8
239000002777 nucleoside Substances 0.000 description 8
150000003833 nucleoside derivatives Chemical class 0.000 description 8
238000003756 stirring Methods 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
125000004122 cyclic group Chemical group 0.000 description 7
238000001514 detection method Methods 0.000 description 7
150000002148 esters Chemical class 0.000 description 7
239000012065 filter cake Substances 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
238000010829 isocratic elution Methods 0.000 description 7
230000014759 maintenance of location Effects 0.000 description 7
239000007858 starting material Substances 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 6
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 6
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 6
HHEOXNRPYVCORL-UHFFFAOYSA-N methyl 5-bromo-8-hydroxy-1,6-naphthyridine-7-carboxylate Chemical compound C1=CC=NC2=C(O)C(C(=O)OC)=NC(Br)=C21 HHEOXNRPYVCORL-UHFFFAOYSA-N 0.000 description 6
125000004076 pyridyl group Chemical group 0.000 description 6
230000002829 reductive effect Effects 0.000 description 6
239000000725 suspension Substances 0.000 description 6
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 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
150000001408 amides Chemical class 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
239000010949 copper Substances 0.000 description 5
238000005859 coupling reaction Methods 0.000 description 5
239000013078 crystal Substances 0.000 description 5
239000000284 extract Substances 0.000 description 5
239000007789 gas Substances 0.000 description 5
125000004043 oxo group Chemical group O=* 0.000 description 5
229910052763 palladium Inorganic materials 0.000 description 5
238000000634 powder X-ray diffraction Methods 0.000 description 5
125000003373 pyrazinyl group Chemical group 0.000 description 5
159000000000 sodium salts Chemical class 0.000 description 5
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 4
FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical group N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 4
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
ACOKNWXGEPFMGV-UHFFFAOYSA-N 4-fluoro-2-methylsulfonylbenzonitrile Chemical compound CS(=O)(=O)C1=CC(F)=CC=C1C#N ACOKNWXGEPFMGV-UHFFFAOYSA-N 0.000 description 4
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
230000037396 body weight Effects 0.000 description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
BERDEBHAJNAUOM-UHFFFAOYSA-N copper(i) oxide Chemical compound [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 4
GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 4
238000001914 filtration Methods 0.000 description 4
238000009472 formulation Methods 0.000 description 4
239000004030 hiv protease inhibitor Substances 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
239000000463 material Substances 0.000 description 4
YXGQKWXSHVOXAQ-UHFFFAOYSA-N methyl 5-bromo-8-(4-methylphenyl)sulfonyloxy-1,6-naphthyridine-7-carboxylate Chemical compound COC(=O)C1=NC(Br)=C2C=CC=NC2=C1OS(=O)(=O)C1=CC=C(C)C=C1 YXGQKWXSHVOXAQ-UHFFFAOYSA-N 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
125000003107 substituted aryl group Chemical group 0.000 description 4
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 4
238000012546 transfer Methods 0.000 description 4
HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 4
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
QZJDWDYPVSMWHX-UHFFFAOYSA-N 4-fluoro-2-methylsulfanylbenzonitrile Chemical compound CSC1=CC(F)=CC=C1C#N QZJDWDYPVSMWHX-UHFFFAOYSA-N 0.000 description 3
VRVGOUHPADQNHC-UHFFFAOYSA-N 5-bromo-n-[(4-fluorophenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound N1=C(Br)C2=CC=CN=C2C(O)=C1C(=O)NCC1=CC=C(F)C=C1 VRVGOUHPADQNHC-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 3
102100032373 Coiled-coil domain-containing protein 85B Human genes 0.000 description 3
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
101000868814 Homo sapiens Coiled-coil domain-containing protein 85B Proteins 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Substances IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 3
239000012300 argon atmosphere Substances 0.000 description 3
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 3
229940125904 compound 1 Drugs 0.000 description 3
229940125773 compound 10 Drugs 0.000 description 3
229940125782 compound 2 Drugs 0.000 description 3
229940126214 compound 3 Drugs 0.000 description 3
229940125898 compound 5 Drugs 0.000 description 3
229910052802 copper Inorganic materials 0.000 description 3
238000010168 coupling process Methods 0.000 description 3
LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 description 3
201000010099 disease Diseases 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
238000004108 freeze drying Methods 0.000 description 3
125000002541 furyl group Chemical group 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
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 3
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
JBNIKIMAOKUJRO-UHFFFAOYSA-N methyl 5-(1,1-dioxothiazinan-2-yl)-8-(4-methylphenyl)sulfonyloxy-1,6-naphthyridine-7-carboxylate Chemical compound C=12C=CC=NC2=C(OS(=O)(=O)C=2C=CC(C)=CC=2)C(C(=O)OC)=NC=1N1CCCCS1(=O)=O JBNIKIMAOKUJRO-UHFFFAOYSA-N 0.000 description 3
WDCSXBRXJCGXNG-UHFFFAOYSA-N methyl 8-hydroxy-1,6-naphthyridine-7-carboxylate Chemical compound C1=CC=NC2=C(O)C(C(=O)OC)=NC=C21 WDCSXBRXJCGXNG-UHFFFAOYSA-N 0.000 description 3
230000004048 modification Effects 0.000 description 3
238000012986 modification Methods 0.000 description 3
125000002950 monocyclic group Chemical group 0.000 description 3
MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
239000003921 oil Substances 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
230000001566 pro-viral effect Effects 0.000 description 3
230000008569 process Effects 0.000 description 3
239000000651 prodrug Substances 0.000 description 3
229940002612 prodrug Drugs 0.000 description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
238000000746 purification Methods 0.000 description 3
125000006413 ring segment Chemical group 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
229910000029 sodium carbonate Inorganic materials 0.000 description 3
238000001228 spectrum Methods 0.000 description 3
239000000126 substance Substances 0.000 description 3
125000000446 sulfanediyl group Chemical group *S* 0.000 description 3
229940124530 sulfonamide Drugs 0.000 description 3
150000003456 sulfonamides Chemical class 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
125000000335 thiazolyl group Chemical group 0.000 description 3
IJOJPUHYXKENFN-UHFFFAOYSA-N (4-fluoro-2-methylsulfonylphenyl)methanamine;hydrochloride Chemical compound Cl.CS(=O)(=O)C1=CC(F)=CC=C1CN IJOJPUHYXKENFN-UHFFFAOYSA-N 0.000 description 2
IIFVWLUQBAIPMJ-UHFFFAOYSA-N (4-fluorophenyl)methanamine Chemical compound NCC1=CC=C(F)C=C1 IIFVWLUQBAIPMJ-UHFFFAOYSA-N 0.000 description 2
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 2
XDQLPJWKJFFSFI-UHFFFAOYSA-N 1,2,5-thiadiazepane 1,1-dioxide Chemical compound O=S1(=O)CCNCCN1 XDQLPJWKJFFSFI-UHFFFAOYSA-N 0.000 description 2
JCTXXFXWHMLHLS-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid;hydrate Chemical compound O.OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O JCTXXFXWHMLHLS-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 2
XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
108010010369 HIV Protease Proteins 0.000 description 2
206010019972 Herpes viral infections Diseases 0.000 description 2
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 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
KJHKTHWMRKYKJE-SUGCFTRWSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O KJHKTHWMRKYKJE-SUGCFTRWSA-N 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
239000012359 Methanesulfonyl chloride Substances 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 2
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 2
MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 description 2
229960004748 abacavir Drugs 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
150000001263 acyl chlorides Chemical class 0.000 description 2
125000000304 alkynyl group Chemical group 0.000 description 2
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
230000002924 anti-infective effect Effects 0.000 description 2
229960005475 antiinfective agent Drugs 0.000 description 2
239000004599 antimicrobial Substances 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
125000004429 atom Chemical group 0.000 description 2
239000002585 base Substances 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
239000004305 biphenyl Substances 0.000 description 2
239000012267 brine Substances 0.000 description 2
230000031709 bromination Effects 0.000 description 2
238000005893 bromination reaction Methods 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
238000001816 cooling Methods 0.000 description 2
230000008878 coupling Effects 0.000 description 2
KRFJLUBVMFXRPN-UHFFFAOYSA-N cuprous oxide Chemical compound [O-2].[Cu+].[Cu+] KRFJLUBVMFXRPN-UHFFFAOYSA-N 0.000 description 2
229940112669 cuprous oxide Drugs 0.000 description 2
MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 2
HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
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 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([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
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 2
239000003814 drug Substances 0.000 description 2
229960003804 efavirenz Drugs 0.000 description 2
XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 description 2
230000000694 effects Effects 0.000 description 2
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 2
239000012458 free base Substances 0.000 description 2
230000002140 halogenating effect Effects 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
125000002883 imidazolyl group Chemical group 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
CBVCZFGXHXORBI-PXQQMZJSSA-N indinavir Chemical compound C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 CBVCZFGXHXORBI-PXQQMZJSSA-N 0.000 description 2
229960001936 indinavir Drugs 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
239000011630 iodine Substances 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
JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropyl acetate Chemical compound CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
238000010902 jet-milling Methods 0.000 description 2
239000010410 layer Substances 0.000 description 2
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
238000004949 mass spectrometry Methods 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
VRDCTKAFGYAUBU-UHFFFAOYSA-N methyl 5-(1,1-dioxothiazinan-2-yl)-8-hydroxy-1,6-naphthyridine-7-carboxylate Chemical compound C=12C=CC=NC2=C(O)C(C(=O)OC)=NC=1N1CCCCS1(=O)=O VRDCTKAFGYAUBU-UHFFFAOYSA-N 0.000 description 2
KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 2
YPRJBICVQVLHJW-UHFFFAOYSA-N n-(2-aminoethyl)ethenesulfonamide;hydrochloride Chemical compound [Cl-].[NH3+]CCNS(=O)(=O)C=C YPRJBICVQVLHJW-UHFFFAOYSA-N 0.000 description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 description 2
239000002773 nucleotide Substances 0.000 description 2
125000003729 nucleotide group Chemical group 0.000 description 2
239000010502 orange oil Substances 0.000 description 2
125000001715 oxadiazolyl group Chemical group 0.000 description 2
125000002971 oxazolyl group Chemical group 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
239000002243 precursor Substances 0.000 description 2
238000002953 preparative HPLC Methods 0.000 description 2
PNMJLJGBBPMRSY-UHFFFAOYSA-N propan-2-yl 3-[[(2-methoxy-2-oxoethyl)-(4-methylphenyl)sulfonylamino]methyl]pyridine-2-carboxylate Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)N(CC(=O)OC)CC1=CC=CN=C1C(=O)OC(C)C PNMJLJGBBPMRSY-UHFFFAOYSA-N 0.000 description 2
125000002098 pyridazinyl group Chemical group 0.000 description 2
125000000714 pyrimidinyl group Chemical group 0.000 description 2
125000000168 pyrrolyl group Chemical group 0.000 description 2
125000001567 quinoxalinyl group Chemical class N1=C(C=NC2=CC=CC=C12)* 0.000 description 2
230000004044 response Effects 0.000 description 2
238000004007 reversed phase HPLC Methods 0.000 description 2
238000007363 ring formation reaction Methods 0.000 description 2
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
238000011894 semi-preparative HPLC Methods 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
150000003457 sulfones Chemical class 0.000 description 2
238000013268 sustained release Methods 0.000 description 2
239000012730 sustained-release form Substances 0.000 description 2
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 2
GVIKIENGBAHDOI-UHFFFAOYSA-N tert-butyl n-[2-(ethenylsulfonylamino)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCNS(=O)(=O)C=C GVIKIENGBAHDOI-UHFFFAOYSA-N 0.000 description 2
125000003831 tetrazolyl group Chemical group 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
238000006276 transfer reaction Methods 0.000 description 2
125000001425 triazolyl group Chemical group 0.000 description 2
241001430294 unidentified retrovirus Species 0.000 description 2
125000000391 vinyl group Chemical class [H]C([*])=C([H])[H] 0.000 description 2
229960002555 zidovudine Drugs 0.000 description 2
125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 description 1
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 1
125000006729 (C2-C5) alkenyl group Chemical group 0.000 description 1
125000006730 (C2-C5) alkynyl group Chemical group 0.000 description 1
125000005871 1,3-benzodioxolyl group Chemical group 0.000 description 1
125000005960 1,4-diazepanyl group Chemical group 0.000 description 1
YKEGCGXXZWOYCF-UHFFFAOYSA-N 1,6-naphthyridine-7-carboxamide Chemical compound C1=CC=C2C=NC(C(=O)N)=CC2=N1 YKEGCGXXZWOYCF-UHFFFAOYSA-N 0.000 description 1
150000005058 1,8-naphthyridines Chemical class 0.000 description 1
125000004973 1-butenyl group Chemical class C(=CCC)* 0.000 description 1
125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
125000004776 1-fluoroethyl group Chemical group [H]C([H])([H])C([H])(F)* 0.000 description 1
PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical group O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
125000006017 1-propenyl group Chemical class 0.000 description 1
125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 1
LJFDXXUKKMEQKE-UHFFFAOYSA-N 2,4-difluorobenzonitrile Chemical compound FC1=CC=C(C#N)C(F)=C1 LJFDXXUKKMEQKE-UHFFFAOYSA-N 0.000 description 1
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 1
125000004974 2-butenyl group Chemical class C(C=CC)* 0.000 description 1
125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
UHNSRUQBYCAURK-UHFFFAOYSA-N 2-fluoro-4-methylsulfonylbenzonitrile Chemical compound CS(=O)(=O)C1=CC=C(C#N)C(F)=C1 UHNSRUQBYCAURK-UHFFFAOYSA-N 0.000 description 1
125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
IWTFOFMTUOBLHG-UHFFFAOYSA-N 2-methoxypyridine Chemical compound COC1=CC=CC=N1 IWTFOFMTUOBLHG-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical class [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
ZTGQZSKPSJUEBU-UHFFFAOYSA-N 3-bromopropan-1-amine Chemical compound NCCCBr ZTGQZSKPSJUEBU-UHFFFAOYSA-N 0.000 description 1
PQIYSSSTRHVOBW-UHFFFAOYSA-N 3-bromopropan-1-amine;hydron;bromide Chemical class Br.NCCCBr PQIYSSSTRHVOBW-UHFFFAOYSA-N 0.000 description 1
125000004975 3-butenyl group Chemical class C(CC=C)* 0.000 description 1
125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
UBOOKRVGOBKDMM-UHFFFAOYSA-N 3h-imidazo[4,5-c]pyridine Chemical compound C1=NC=C2NC=NC2=C1 UBOOKRVGOBKDMM-UHFFFAOYSA-N 0.000 description 1
LHCOVOKZWQYODM-CPEOKENHSA-N 4-amino-1-[(2r,5s)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one;1-[(2r,4s,5s)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1.O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 LHCOVOKZWQYODM-CPEOKENHSA-N 0.000 description 1
RINRLYXWGIBGMT-UHFFFAOYSA-N 4-oxo-1h-quinoline-2-carboxamide Chemical class C1=CC=CC2=NC(C(=O)N)=CC(O)=C21 RINRLYXWGIBGMT-UHFFFAOYSA-N 0.000 description 1
ADFYNTZFPWWXAK-UHFFFAOYSA-N 5-(1,1-dioxothiazinan-2-yl)-n-[(4-fluoro-2-methylsulfonylphenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound CS(=O)(=O)C1=CC(F)=CC=C1CNC(=O)C1=NC(N2S(CCCC2)(=O)=O)=C(C=CC=N2)C2=C1O ADFYNTZFPWWXAK-UHFFFAOYSA-N 0.000 description 1
SSKJBFGODNGAAF-UHFFFAOYSA-N 5-(1,5-dioxo-1,4-thiazepan-7-yl)-n-[(4-fluorophenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound C12=CC=CN=C2C(O)=C(C(=O)NCC=2C=CC(F)=CC=2)N=C1C1CC(=O)NCCS1=O SSKJBFGODNGAAF-UHFFFAOYSA-N 0.000 description 1
UOXJJAWUHWTXIN-UHFFFAOYSA-N 5-(2-aminoethylamino)-n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound OC=1C2=NC=CC=C2C(NCCN)=NC=1C(=O)NCC1=CC(Cl)=CC(Cl)=C1 UOXJJAWUHWTXIN-UHFFFAOYSA-N 0.000 description 1
ZUDWJSDKIDRGHM-UHFFFAOYSA-N 5-(3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazin-2-yl)-n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound N1=C(N2CC3CCCN3CC2)C2=CC=CN=C2C(O)=C1C(=O)NCC1=CC(Cl)=CC(Cl)=C1 ZUDWJSDKIDRGHM-UHFFFAOYSA-N 0.000 description 1
FGCJBJRTTDGQTK-UHFFFAOYSA-N 5-(3-aminopyrrolidin-1-yl)-n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1C(N)CCN1C1=NC(C(=O)NCC=2C=C(Cl)C=C(Cl)C=2)=C(O)C2=NC=CC=C12 FGCJBJRTTDGQTK-UHFFFAOYSA-N 0.000 description 1
CMDHXSMHDPAKPW-UHFFFAOYSA-N 5-(benzenesulfonyl)-n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound C12=CC=CN=C2C(O)=C(C(=O)NCC=2C=C(Cl)C=C(Cl)C=2)N=C1S(=O)(=O)C1=CC=CC=C1 CMDHXSMHDPAKPW-UHFFFAOYSA-N 0.000 description 1
ULRULKDUOLZKHU-UHFFFAOYSA-N 5-(cyclopropylmethylamino)-n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound C12=CC=CN=C2C(O)=C(C(=O)NCC=2C=C(Cl)C=C(Cl)C=2)N=C1NCC1CC1 ULRULKDUOLZKHU-UHFFFAOYSA-N 0.000 description 1
MQTICBWDXKHKQC-UHFFFAOYSA-N 5-[2-aminoethyl(benzyl)amino]-n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound N=1C(C(=O)NCC=2C=C(Cl)C=C(Cl)C=2)=C(O)C2=NC=CC=C2C=1N(CCN)CC1=CC=CC=C1 MQTICBWDXKHKQC-UHFFFAOYSA-N 0.000 description 1
WCPIDSOAYNZXII-UHFFFAOYSA-N 5-[4-(2-aminoethyl)piperazin-1-yl]-n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound C1CN(CCN)CCN1C1=NC(C(=O)NCC=2C=C(Cl)C=C(Cl)C=2)=C(O)C2=NC=CC=C12 WCPIDSOAYNZXII-UHFFFAOYSA-N 0.000 description 1
VDGZGJBZUCUGHZ-UHFFFAOYSA-N 5-benzyl-N,2-dimethyl-1-oxo-4-pyrrolidin-1-yl-N-(trifluoromethyl)isoquinoline-3-carboxamide Chemical compound C(C1=CC=CC=C1)C1=C2C(=C(N(C(C2=CC=C1)=O)C)C(=O)N(C)C(F)(F)F)N1CCCC1 VDGZGJBZUCUGHZ-UHFFFAOYSA-N 0.000 description 1
OCPSLKOEQVGAIK-UHFFFAOYSA-N 5-bromo-n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound N1=C(Br)C2=CC=CN=C2C(O)=C1C(=O)NCC1=CC(Cl)=CC(Cl)=C1 OCPSLKOEQVGAIK-UHFFFAOYSA-N 0.000 description 1
IYUJZQJMBQMDQO-UHFFFAOYSA-N 5-chloro-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound C1=CC=NC2=C(O)C(C(=O)N)=NC(Cl)=C21 IYUJZQJMBQMDQO-UHFFFAOYSA-N 0.000 description 1
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 1
YBYNBJQECLWGMU-ZDUSSCGKSA-N 8-hydroxy-n-[(1r)-2-hydroxy-1-phenylethyl]-1,6-naphthyridine-7-carboxamide Chemical compound C1([C@@H](NC(=O)C=2C(=C3N=CC=CC3=CN=2)O)CO)=CC=CC=C1 YBYNBJQECLWGMU-ZDUSSCGKSA-N 0.000 description 1
QHDZLNBTKUXQTB-WOJBJXKFSA-N 8-hydroxy-n-[(1r,3r)-3-phenyl-2,3-dihydro-1h-inden-1-yl]-1,6-naphthyridine-7-carboxamide Chemical compound C1([C@H]2C[C@H](C3=CC=CC=C32)NC(=O)C2=C(C3=NC=CC=C3C=N2)O)=CC=CC=C1 QHDZLNBTKUXQTB-WOJBJXKFSA-N 0.000 description 1
MMPCZAZWHKQEKH-NSHDSACASA-N 8-hydroxy-n-[(1s)-1-phenylethyl]-1,6-naphthyridine-7-carboxamide Chemical compound C1([C@@H](NC(=O)C=2C(=C3N=CC=CC3=CN=2)O)C)=CC=CC=C1 MMPCZAZWHKQEKH-NSHDSACASA-N 0.000 description 1
NEJFQZQRYADVDX-UHFFFAOYSA-N 8-hydroxy-n-[(2-methylsulfanylphenyl)methyl]-5-phenylsulfanyl-1,6-naphthyridine-7-carboxamide Chemical compound CSC1=CC=CC=C1CNC(=O)C1=NC(SC=2C=CC=CC=2)=C(C=CC=N2)C2=C1O NEJFQZQRYADVDX-UHFFFAOYSA-N 0.000 description 1
RPXBMGACCSLYOD-UHFFFAOYSA-N 8-hydroxy-n-[(2-phenylphenyl)methyl]-1,6-naphthyridine-7-carboxamide Chemical compound N1=CC2=CC=CN=C2C(O)=C1C(=O)NCC1=CC=CC=C1C1=CC=CC=C1 RPXBMGACCSLYOD-UHFFFAOYSA-N 0.000 description 1
MTTZCNWOJKHBNR-AWEZNQCLSA-N 8-hydroxy-n-[(2s)-1-hydroxy-3-phenylpropan-2-yl]-1,6-naphthyridine-7-carboxamide Chemical compound C([C@@H](CO)NC(=O)C=1C(=C2N=CC=CC2=CN=1)O)C1=CC=CC=C1 MTTZCNWOJKHBNR-AWEZNQCLSA-N 0.000 description 1
NLMGXKRVIOBUTI-UHFFFAOYSA-N 8-hydroxy-n-[(3-phenylphenyl)methyl]-1,6-naphthyridine-7-carboxamide Chemical compound N1=CC2=CC=CN=C2C(O)=C1C(=O)NCC(C=1)=CC=CC=1C1=CC=CC=C1 NLMGXKRVIOBUTI-UHFFFAOYSA-N 0.000 description 1
FOXMISVOVQTSGS-UHFFFAOYSA-N 8-hydroxyquinoline-7-carboxamide Chemical class C1=CC=NC2=C(O)C(C(=O)N)=CC=C21 FOXMISVOVQTSGS-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
206010000807 Acute HIV infection Diseases 0.000 description 1
102000002260 Alkaline Phosphatase Human genes 0.000 description 1
108020004774 Alkaline Phosphatase Proteins 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
229910014265 BrCl Inorganic materials 0.000 description 1
LOQMWQVAJVWEEO-UHFFFAOYSA-N CN(C1=NC(=C(C2=C1C=CC=N2)COC(=O)C(=O)O)C(=O)NCC3=CC=C(C=C3)F)C(=O)C(=O)OC Chemical compound CN(C1=NC(=C(C2=C1C=CC=N2)COC(=O)C(=O)O)C(=O)NCC3=CC=C(C=C3)F)C(=O)C(=O)OC LOQMWQVAJVWEEO-UHFFFAOYSA-N 0.000 description 1
QAGYKUNXZHXKMR-UHFFFAOYSA-N CPD000469186 Natural products CC1=C(O)C=CC=C1C(=O)NC(C(O)CN1C(CC2CCCCC2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-UHFFFAOYSA-N 0.000 description 1
229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
229910004373 HOAc Inorganic materials 0.000 description 1
241000282412 Homo Species 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
OFFWOVJBSQMVPI-RMLGOCCBSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O.N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 OFFWOVJBSQMVPI-RMLGOCCBSA-N 0.000 description 1
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 1
238000005684 Liebig rearrangement reaction Methods 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
150000001204 N-oxides Chemical class 0.000 description 1
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
102000011931 Nucleoproteins Human genes 0.000 description 1
108010061100 Nucleoproteins Proteins 0.000 description 1
108700026244 Open Reading Frames Proteins 0.000 description 1
239000008896 Opium Substances 0.000 description 1
CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 1
229910004298 SiO 2 Inorganic materials 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
XNKLLVCARDGLGL-JGVFFNPUSA-N Stavudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](CO)O1 XNKLLVCARDGLGL-JGVFFNPUSA-N 0.000 description 1
108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
108020005202 Viral DNA Proteins 0.000 description 1
241000700605 Viruses Species 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
239000003377 acid catalyst Substances 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000006978 adaptation Effects 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
125000003172 aldehyde group Chemical group 0.000 description 1
150000001335 aliphatic alkanes Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
238000007112 amidation reaction Methods 0.000 description 1
150000001413 amino acids Chemical group 0.000 description 1
238000007098 aminolysis reaction Methods 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
229960001830 amprenavir Drugs 0.000 description 1
YMARZQAQMVYCKC-OEMFJLHTSA-N amprenavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 YMARZQAQMVYCKC-OEMFJLHTSA-N 0.000 description 1
SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 1
230000000840 anti-viral effect Effects 0.000 description 1
229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
239000003849 aromatic solvent Substances 0.000 description 1
125000001769 aryl amino group Chemical group 0.000 description 1
125000004104 aryloxy group Chemical group 0.000 description 1
125000003725 azepanyl group Chemical group 0.000 description 1
125000002785 azepinyl group Chemical group 0.000 description 1
230000008901 benefit Effects 0.000 description 1
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
150000003939 benzylamines Chemical class 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
239000012455 biphasic mixture Substances 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
125000005620 boronic acid group Chemical class 0.000 description 1
CODNYICXDISAEA-UHFFFAOYSA-N bromine monochloride Chemical compound BrCl CODNYICXDISAEA-UHFFFAOYSA-N 0.000 description 1
150000001649 bromium compounds Chemical class 0.000 description 1
229910052792 caesium Inorganic materials 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
230000006315 carbonylation Effects 0.000 description 1
238000005810 carbonylation reaction Methods 0.000 description 1
150000003857 carboxamides Chemical class 0.000 description 1
125000005518 carboxamido group Chemical class 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
150000007942 carboxylates Chemical class 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
230000008859 change Effects 0.000 description 1
239000002026 chloroform extract Substances 0.000 description 1
125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
238000004040 coloring Methods 0.000 description 1
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
238000004132 cross linking Methods 0.000 description 1
239000012043 crude product Substances 0.000 description 1
238000007333 cyanation reaction Methods 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
230000006378 damage Effects 0.000 description 1
230000007850 degeneration Effects 0.000 description 1
WHBIGIKBNXZKFE-UHFFFAOYSA-N delavirdine mesylate Natural products CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(NS(C)(=O)=O)C=C3C=2)CC1 WHBIGIKBNXZKFE-UHFFFAOYSA-N 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
150000004985 diamines Chemical class 0.000 description 1
125000005959 diazepanyl group Chemical group 0.000 description 1
229960002656 didanosine Drugs 0.000 description 1
238000000113 differential scanning calorimetry Methods 0.000 description 1
238000001938 differential scanning calorimetry curve Methods 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
125000006263 dimethyl aminosulfonyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])S(*)(=O)=O 0.000 description 1
229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
238000011038 discontinuous diafiltration by volume reduction Methods 0.000 description 1
231100000676 disease causative agent Toxicity 0.000 description 1
KAKKHKRHCKCAGH-UHFFFAOYSA-L disodium;(4-nitrophenyl) phosphate;hexahydrate Chemical compound O.O.O.O.O.O.[Na+].[Na+].[O-][N+](=O)C1=CC=C(OP([O-])([O-])=O)C=C1 KAKKHKRHCKCAGH-UHFFFAOYSA-L 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
238000009510 drug design Methods 0.000 description 1
238000007876 drug discovery Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000003480 eluent Substances 0.000 description 1
238000010828 elution Methods 0.000 description 1
GJCMPSFDXTZWFO-UHFFFAOYSA-N ethyl 4-[2,5-dioxo-3-[2-oxo-2-(4-sulfamoylanilino)ethyl]sulfanylpyrrolidin-1-yl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1N1C(=O)C(SCC(=O)NC=2C=CC(=CC=2)S(N)(=O)=O)CC1=O GJCMPSFDXTZWFO-UHFFFAOYSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
230000029142 excretion Effects 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
238000000605 extraction Methods 0.000 description 1
RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 1
MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
150000004795 grignard reagents Chemical class 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000001188 haloalkyl group Chemical group 0.000 description 1
230000036541 health Effects 0.000 description 1
150000002390 heteroarenes Chemical class 0.000 description 1
150000002391 heterocyclic compounds Chemical class 0.000 description 1
125000004634 hexahydroazepinyl group Chemical group N1(CCCCCC1)* 0.000 description 1
238000004896 high resolution mass spectrometry Methods 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
239000012456 homogeneous solution Substances 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
125000002632 imidazolidinyl group Chemical group 0.000 description 1
125000002636 imidazolinyl group Chemical group 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
239000012535 impurity Substances 0.000 description 1
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
238000001802 infusion Methods 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
230000010354 integration Effects 0.000 description 1
230000002452 interceptive effect Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
MGIYRDNGCNKGJU-UHFFFAOYSA-N isothiazolinone Chemical compound O=C1C=CSN1 MGIYRDNGCNKGJU-UHFFFAOYSA-N 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
229940112586 kaletra Drugs 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000008101 lactose Substances 0.000 description 1
229960001627 lamivudine Drugs 0.000 description 1
JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
229960004525 lopinavir Drugs 0.000 description 1
229940120922 lopinavir and ritonavir Drugs 0.000 description 1
238000003760 magnetic stirring Methods 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
238000004519 manufacturing process Methods 0.000 description 1
230000035800 maturation Effects 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
LSDPWZHWYPCBBB-UHFFFAOYSA-M methanethiolate Chemical compound [S-]C LSDPWZHWYPCBBB-UHFFFAOYSA-M 0.000 description 1
238000006140 methanolysis reaction Methods 0.000 description 1
GYQBPYXMRNEAKZ-UHFFFAOYSA-N methyl 2-[(4-methylphenyl)sulfonylamino]acetate Chemical compound COC(=O)CNS(=O)(=O)C1=CC=C(C)C=C1 GYQBPYXMRNEAKZ-UHFFFAOYSA-N 0.000 description 1
ZXUQEPZWVQIOJE-UHFFFAOYSA-N methyl 2-chloro-2-oxoacetate Chemical compound COC(=O)C(Cl)=O ZXUQEPZWVQIOJE-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
238000002156 mixing Methods 0.000 description 1
RAQWHSLAOXPLLF-UHFFFAOYSA-N n-(1,2-diphenylethyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound N1=CC2=CC=CN=C2C(O)=C1C(=O)NC(C=1C=CC=CC=1)CC1=CC=CC=C1 RAQWHSLAOXPLLF-UHFFFAOYSA-N 0.000 description 1
TZXAEGHYLIIQTE-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-1-yl)-8-hydroxy-5-phenyl-1,6-naphthyridine-7-carboxamide Chemical compound C12=CC=CN=C2C(O)=C(C(=O)NC2C3=CC=CC=C3CC2)N=C1C1=CC=CC=C1 TZXAEGHYLIIQTE-UHFFFAOYSA-N 0.000 description 1
FXBKXTMULGSDTD-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-1-ylmethyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound C1CC2=CC=CC=C2C1CNC(=O)C1=C(O)C2=NC=CC=C2C=N1 FXBKXTMULGSDTD-UHFFFAOYSA-N 0.000 description 1
CODPDEUURMCITK-AWEZNQCLSA-N n-[(1s)-2,3-dihydro-1h-inden-1-yl]-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound C1CC2=CC=CC=C2[C@H]1NC(=O)C1=C(O)C2=NC=CC=C2C=N1 CODPDEUURMCITK-AWEZNQCLSA-N 0.000 description 1
XDWSBPJGAYOXRQ-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-5-[2-(dimethylamino)ethyl-methylamino]-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound OC=1C2=NC=CC=C2C(N(C)CCN(C)C)=NC=1C(=O)NCC1=CC(Cl)=CC(Cl)=C1 XDWSBPJGAYOXRQ-UHFFFAOYSA-N 0.000 description 1
DDNFQVNOPLWISH-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound N1=CC2=CC=CN=C2C(O)=C1C(=O)NCC1=CC(Cl)=CC(Cl)=C1 DDNFQVNOPLWISH-UHFFFAOYSA-N 0.000 description 1
DQMYXBAVTMRNAH-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-5-(1,2,4-triazol-1-yl)-1,6-naphthyridine-7-carboxamide Chemical compound C12=CC=CN=C2C(O)=C(C(=O)NCC=2C=C(Cl)C=C(Cl)C=2)N=C1N1C=NC=N1 DQMYXBAVTMRNAH-UHFFFAOYSA-N 0.000 description 1
BOOOMABWYITNIN-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-5-(3-hydroxyprop-1-ynyl)-1,6-naphthyridine-7-carboxamide Chemical compound OC=1C2=NC=CC=C2C(C#CCO)=NC=1C(=O)NCC1=CC(Cl)=CC(Cl)=C1 BOOOMABWYITNIN-UHFFFAOYSA-N 0.000 description 1
PXHIKNIIRYKXSO-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-5-(3-hydroxypyrrolidin-1-yl)-1,6-naphthyridine-7-carboxamide Chemical compound C1C(O)CCN1C1=NC(C(=O)NCC=2C=C(Cl)C=C(Cl)C=2)=C(O)C2=NC=CC=C12 PXHIKNIIRYKXSO-UHFFFAOYSA-N 0.000 description 1
NYNNRBJQZXXJIJ-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-5-(3-morpholin-4-ylprop-1-ynyl)-1,6-naphthyridine-7-carboxamide Chemical compound C12=CC=CN=C2C(O)=C(C(=O)NCC=2C=C(Cl)C=C(Cl)C=2)N=C1C#CCN1CCOCC1 NYNNRBJQZXXJIJ-UHFFFAOYSA-N 0.000 description 1
RCKJNNFDGJOVAQ-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-5-(3-piperidin-1-ylprop-1-ynyl)-1,6-naphthyridine-7-carboxamide Chemical compound C12=CC=CN=C2C(O)=C(C(=O)NCC=2C=C(Cl)C=C(Cl)C=2)N=C1C#CCN1CCCCC1 RCKJNNFDGJOVAQ-UHFFFAOYSA-N 0.000 description 1
CRKMQOHLYHPZFH-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-5-(4-pyrrolidin-1-ylpiperidin-1-yl)-1,6-naphthyridine-7-carboxamide Chemical compound C12=CC=CN=C2C(O)=C(C(=O)NCC=2C=C(Cl)C=C(Cl)C=2)N=C1N(CC1)CCC1N1CCCC1 CRKMQOHLYHPZFH-UHFFFAOYSA-N 0.000 description 1
MPHJQEBRPPYQHF-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-5-(pyridin-4-ylamino)-1,6-naphthyridine-7-carboxamide Chemical compound C12=CC=CN=C2C(O)=C(C(=O)NCC=2C=C(Cl)C=C(Cl)C=2)N=C1NC1=CC=NC=C1 MPHJQEBRPPYQHF-UHFFFAOYSA-N 0.000 description 1
PGJZHWLHHNLASX-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-5-[3-(4-methylpiperazin-1-yl)propylamino]-1,6-naphthyridine-7-carboxamide Chemical compound C1CN(C)CCN1CCCNC1=NC(C(=O)NCC=2C=C(Cl)C=C(Cl)C=2)=C(O)C2=NC=CC=C12 PGJZHWLHHNLASX-UHFFFAOYSA-N 0.000 description 1
GYOMDIVFOMZZCQ-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-5-[4-(2-oxo-2-pyrrolidin-1-ylethyl)piperazin-1-yl]-1,6-naphthyridine-7-carboxamide Chemical compound C12=CC=CN=C2C(O)=C(C(=O)NCC=2C=C(Cl)C=C(Cl)C=2)N=C1N(CC1)CCN1CC(=O)N1CCCC1 GYOMDIVFOMZZCQ-UHFFFAOYSA-N 0.000 description 1
NBZXMMOMDCMIQG-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-5-[4-(2-phenylethyl)piperazin-1-yl]-1,6-naphthyridine-7-carboxamide Chemical compound C12=CC=CN=C2C(O)=C(C(=O)NCC=2C=C(Cl)C=C(Cl)C=2)N=C1N(CC1)CCN1CCC1=CC=CC=C1 NBZXMMOMDCMIQG-UHFFFAOYSA-N 0.000 description 1
WWAIWWQZMYVHNL-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-5-phenylsulfanyl-1,6-naphthyridine-7-carboxamide Chemical compound C12=CC=CN=C2C(O)=C(C(=O)NCC=2C=C(Cl)C=C(Cl)C=2)N=C1SC1=CC=CC=C1 WWAIWWQZMYVHNL-UHFFFAOYSA-N 0.000 description 1
PIFNFMPMIQRPDW-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-5-piperazin-1-yl-1,6-naphthyridine-7-carboxamide Chemical compound C12=CC=CN=C2C(O)=C(C(=O)NCC=2C=C(Cl)C=C(Cl)C=2)N=C1N1CCNCC1 PIFNFMPMIQRPDW-UHFFFAOYSA-N 0.000 description 1
QGXYWOMWDMKIEM-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-8-hydroxy-6-methyl-5h-1,6-naphthyridine-7-carboxamide Chemical compound CN1CC2=CC=CN=C2C(O)=C1C(=O)NCC1=CC(Cl)=CC(Cl)=C1 QGXYWOMWDMKIEM-UHFFFAOYSA-N 0.000 description 1
YZTWHZCMZKCCGU-UHFFFAOYSA-N n-[(4-chlorophenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound N1=CC2=CC=CN=C2C(O)=C1C(=O)NCC1=CC=C(Cl)C=C1 YZTWHZCMZKCCGU-UHFFFAOYSA-N 0.000 description 1
HLLMSPCWQWRDAM-UHFFFAOYSA-N n-[(4-fluoro-2-methylsulfonylphenyl)methyl]-8-hydroxy-5-[methyl-(1-methylimidazol-4-yl)sulfonylamino]-1,6-naphthyridine-7-carboxamide Chemical compound C=1N(C)C=NC=1S(=O)(=O)N(C)C(C1=CC=CN=C1C=1O)=NC=1C(=O)NCC1=CC=C(F)C=C1S(C)(=O)=O HLLMSPCWQWRDAM-UHFFFAOYSA-N 0.000 description 1
LQCQPBUEUDRVLA-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-8-hydroxy-5-(4-methylpiperazin-1-yl)-1,6-naphthyridine-7-carboxamide Chemical compound C1CN(C)CCN1C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C2=NC=CC=C12 LQCQPBUEUDRVLA-UHFFFAOYSA-N 0.000 description 1
VREWQJLHOCORCY-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-8-hydroxy-5-(5-oxo-1,4-thiazepan-7-yl)-1,6-naphthyridine-7-carboxamide Chemical compound C12=CC=CN=C2C(O)=C(C(=O)NCC=2C=CC(F)=CC=2)N=C1C1CC(=O)NCCS1 VREWQJLHOCORCY-UHFFFAOYSA-N 0.000 description 1
DDCRTNPPGCWMEL-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-8-hydroxy-5-(methylamino)-1,6-naphthyridine-7-carboxamide Chemical compound OC=1C2=NC=CC=C2C(NC)=NC=1C(=O)NCC1=CC=C(F)C=C1 DDCRTNPPGCWMEL-UHFFFAOYSA-N 0.000 description 1
OGNMBDBLPZXYGO-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-8-hydroxy-5-[2-(2-oxoimidazolidin-1-yl)ethyl]-1,6-naphthyridine-7-carboxamide Chemical compound C12=CC=CN=C2C(O)=C(C(=O)NCC=2C=CC(F)=CC=2)N=C1CCN1CCNC1=O OGNMBDBLPZXYGO-UHFFFAOYSA-N 0.000 description 1
XTTJNNWYVFBGFL-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-8-hydroxy-5-[2-(2-oxopiperazin-1-yl)ethyl]-1,6-naphthyridine-7-carboxamide Chemical compound C12=CC=CN=C2C(O)=C(C(=O)NCC=2C=CC(F)=CC=2)N=C1CCN1CCNCC1=O XTTJNNWYVFBGFL-UHFFFAOYSA-N 0.000 description 1
PGNJQJSGUAOGNQ-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-8-hydroxy-5-piperazin-1-yl-1,6-naphthyridine-7-carboxamide Chemical compound C12=CC=CN=C2C(O)=C(C(=O)NCC=2C=CC(F)=CC=2)N=C1N1CCNCC1 PGNJQJSGUAOGNQ-UHFFFAOYSA-N 0.000 description 1
YETBUVUUAFDTCG-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-8-hydroxy-6-methyl-5h-1,6-naphthyridine-7-carboxamide Chemical compound CN1CC2=CC=CN=C2C(O)=C1C(=O)NCC1=CC=C(F)C=C1 YETBUVUUAFDTCG-UHFFFAOYSA-N 0.000 description 1
SGMJOCRZHPWSJI-UHFFFAOYSA-N n-[2-(4-chlorophenyl)ethyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound N1=CC2=CC=CN=C2C(O)=C1C(=O)NCCC1=CC=C(Cl)C=C1 SGMJOCRZHPWSJI-UHFFFAOYSA-N 0.000 description 1
GOJUTGQPTKVFPX-UHFFFAOYSA-N n-[5-(2-fluoro-5-hydroxy-4-methylanilino)-1,8-naphthyridin-2-yl]acetamide Chemical compound C=1C=NC2=NC(NC(=O)C)=CC=C2C=1NC1=CC(O)=C(C)C=C1F GOJUTGQPTKVFPX-UHFFFAOYSA-N 0.000 description 1
150000005054 naphthyridines Chemical class 0.000 description 1
QAGYKUNXZHXKMR-HKWSIXNMSA-N nelfinavir Chemical compound CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-HKWSIXNMSA-N 0.000 description 1
229960000884 nelfinavir Drugs 0.000 description 1
229960000689 nevirapine Drugs 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
235000016709 nutrition Nutrition 0.000 description 1
230000035764 nutrition Effects 0.000 description 1
229940049964 oleate Drugs 0.000 description 1
229960001027 opium Drugs 0.000 description 1
125000000160 oxazolidinyl group Chemical group 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
239000002245 particle Substances 0.000 description 1
125000002255 pentenyl group Chemical class C(=CCCC)* 0.000 description 1
125000005981 pentynyl group Chemical group 0.000 description 1
239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
125000005005 perfluorohexyl group Chemical group FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)* 0.000 description 1
210000001428 peripheral nervous system Anatomy 0.000 description 1
239000008177 pharmaceutical agent Substances 0.000 description 1
ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
108700004029 pol Genes Proteins 0.000 description 1
101150088264 pol gene Proteins 0.000 description 1
239000003880 polar aprotic solvent Substances 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
239000013014 purified material Substances 0.000 description 1
125000003072 pyrazolidinyl group Chemical group 0.000 description 1
125000002755 pyrazolinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
238000010791 quenching Methods 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
150000003248 quinolines Chemical class 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
230000005855 radiation Effects 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
108091006082 receptor inhibitors Proteins 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000008439 repair process Effects 0.000 description 1
NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 1
229960000311 ritonavir Drugs 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 1
229960001852 saquinavir Drugs 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000010956 selective crystallization Methods 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
JXHZRQHZVYDRGX-UHFFFAOYSA-M sodium;hydrogen sulfate;hydrate Chemical compound [OH-].[Na+].OS(O)(=O)=O JXHZRQHZVYDRGX-UHFFFAOYSA-M 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
239000000758 substrate Substances 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
CWLVFOOPGRZQMZ-UHFFFAOYSA-N tert-butyl 1,1-dioxo-1,2,5-thiadiazepane-5-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNS(=O)(=O)CC1 CWLVFOOPGRZQMZ-UHFFFAOYSA-N 0.000 description 1
YEBBRWKNKIJVPW-UHFFFAOYSA-N tert-butyl 2-[7-[(4-fluorophenyl)methylcarbamoyl]-8-hydroxy-1,6-naphthyridin-5-yl]-1,1-dioxo-1,2,5-thiadiazepane-5-carboxylate Chemical compound O=S1(=O)CCN(C(=O)OC(C)(C)C)CCN1C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C2=NC=CC=C12 YEBBRWKNKIJVPW-UHFFFAOYSA-N 0.000 description 1
AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 1
CDGMTZPYNBYLPQ-UHFFFAOYSA-N tert-butyl n-[1-[7-[(3,5-dichlorophenyl)methylcarbamoyl]-8-hydroxy-1,6-naphthyridin-5-yl]pyrrolidin-3-yl]carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)CCN1C1=NC(C(=O)NCC=2C=C(Cl)C=C(Cl)C=2)=C(O)C2=NC=CC=C12 CDGMTZPYNBYLPQ-UHFFFAOYSA-N 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
DNGMYXZLJGHHOM-UHFFFAOYSA-N thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCCCN1 DNGMYXZLJGHHOM-UHFFFAOYSA-N 0.000 description 1
125000006407 thiazinanyl group Chemical group 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
125000004569 thiomorpholin-2-yl group Chemical group N1CC(SCC1)* 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
125000000464 thioxo group Chemical group S=* 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
229940111527 trizivir Drugs 0.000 description 1
239000010981 turquoise Substances 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
239000003643 water by type Substances 0.000 description 1
229960000523 zalcitabine Drugs 0.000 description 1

Classifications

- 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
- 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
- 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
- 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
- A61P31/18—Antivirals for RNA viruses for HIV

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Public Health (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
Virology (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
AIDS & HIV (AREA)
Tropical Medicine & Parasitology (AREA)
Molecular Biology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

SK432-2003A 2000-10-12 2001-10-09 Aza- and polyaza-naphthalenyl carboxamides useful as HIV integrase inhibitors SK4322003A3 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US23970700P	2000-10-12	2000-10-12
US28165601P	2001-04-05	2001-04-05
PCT/US2001/042564 WO2002030931A2 (en)	2000-10-12	2001-10-09	Aza- and polyaza-naphthalenyl carboxamides useful as hiv integrase inhibitors

Publications (1)

Publication Number	Publication Date
SK4322003A3 true SK4322003A3 (en)	2003-09-11

Family

ID=26932782

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK432-2003A SK4322003A3 (en)	2000-10-12	2001-10-09	Aza- and polyaza-naphthalenyl carboxamides useful as HIV integrase inhibitors

Country Status (26)

Country	Link
US (2)	US6921759B2 (cs)
EP (1)	EP1326865B1 (cs)
JP (1)	JP4252797B2 (cs)
KR (1)	KR20030036922A (cs)
CN (1)	CN1469878A (cs)
AR (1)	AR033845A1 (cs)
AT (1)	ATE430745T1 (cs)
AU (3)	AU1152702A (cs)
BG (1)	BG107677A (cs)
BR (1)	BR0114610A (cs)
CA (1)	CA2425440C (cs)
CZ (1)	CZ20031028A3 (cs)
DE (1)	DE60138635D1 (cs)
EA (1)	EA200300449A1 (cs)
EE (1)	EE200300145A (cs)
HU (1)	HUP0302367A2 (cs)
IL (1)	IL155089A0 (cs)
IS (1)	IS6760A (cs)
MX (1)	MXPA03003263A (cs)
NO (1)	NO20031672L (cs)
NZ (1)	NZ525088A (cs)
PE (1)	PE20020509A1 (cs)
PL (1)	PL360944A1 (cs)
SK (1)	SK4322003A3 (cs)
WO (2)	WO2002030931A2 (cs)
YU (1)	YU27903A (cs)

Families Citing this family (93)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ATE430745T1 (de) *	2000-10-12	2009-05-15	Merck & Co Inc	Aza- und polyaza naphthalenyl karboxamide als inhibitoren der hiv-integrase
TWI243164B (en)	2001-02-13	2005-11-11	Aventis Pharma Gmbh	Acylated indanyl amines and their use as pharmaceuticals
IL157638A0 (en) *	2001-03-01	2004-03-28	Shionogi & Co	Nitrogen-containing heteroaryl compounds having hiv integrase inhibitory activity
DK3042894T1 (da)	2001-08-10	2016-11-07	Shionogi & Co	Antiviralt middel
AR036256A1 (es) *	2001-08-17	2004-08-25	Merck & Co Inc	Sal sodica de un inhibidor de integrasa del vih, procesos para su preparacion, composiciones farmaceuticas que lo contienen y su uso para la manufactura de un medicamento
WO2003016294A1 (en) *	2001-08-17	2003-02-27	Merck & Co., Inc.	Process for preparing sultams
EP1427726A1 (en) *	2001-08-17	2004-06-16	Merck & Co., Inc.	Process for preparing 5-sulfonamido-8-hydroxy-1, 6-naphthyridine-7-carboxamides
DE60209381T2 (de) *	2001-10-26	2006-10-05	Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A.	N-substituierte hydroxypyrimidinoncarboxamid-hemmer der hiv-integrase
SI1441734T1 (sl)	2001-10-26	2007-08-31	Angeletti P Ist Richerche Bio	Dihidropirimidin karboksamidni inhibitorji HIV-integraze
DE10155075A1 (de)	2001-11-09	2003-05-22	Merck Patent Gmbh	Cyclische Sulfonamide
ES2291642T3 (es)	2002-01-17	2008-03-01	MERCK & CO., INC.	Hidroxinaftiridinoncarboxamidas utiles como inhibidores de la integrasa de vih.
AU2003218130A1 (en)	2002-03-15	2003-09-29	Merck And Co., Inc.	N-(substituted benzyl)-8-hydroxy-1,6-naphthyridine-7- carboxamides useful as hiv integrase inhibitors
US20050165000A1 (en) *	2002-04-10	2005-07-28	Robertson Sandra K.	Pharmaceutical compositions containing an hiv integrase inhibitor and a nonionic surfactant
AU2003269878A1 (en) *	2002-05-22	2003-12-22	Smithkline Beecham Corporation	Protease inhibitors
EP1388535A1 (en) *	2002-08-07	2004-02-11	Aventis Pharma Deutschland GmbH	Acylated arylcycloalkylamines and their use as pharmaceuticals
DE60322920D1 (de) *	2002-08-13	2008-09-25	Shionogi & Co	Heterocyclische verbindungen mit hiv-integrase-hemmender wirkung
US7399763B2 (en)	2002-09-11	2008-07-15	Merck & Co., Inc.	8-hydroxy-1-oxo-tetrahydropyrrolopyrazine compounds useful as HIV integrase inhibitors
US7517532B2 (en)	2002-09-11	2009-04-14	Merck & Co., Inc.	Dihydroxypyridopyrazine-1,6-dione compounds useful as HIV integrase inhibitors
EP1558585B1 (en)	2002-10-04	2013-09-25	Prana Biotechnology Limited	Neurologically-active compounds
AU2003284001A1 (en)	2002-10-07	2004-05-04	Bristol-Myers Squibb Company	Triazolone and triazolethione derivatives
WO2004035577A2 (en) *	2002-10-16	2004-04-29	Gilead Sciences, Inc.	Pre-organized tricyclic integrase inhibitor compounds
BR0317749A (pt)	2002-12-27	2005-11-22	Angeletti P Ist Richerche Bio	Composto, composição farmacêutica, e, uso de um composto
WO2004080402A2 (en) *	2003-03-12	2004-09-23	Merck & Co. Inc.	Potassium salt of an hiv integrase inhibitor
US20040220273A1 (en) *	2003-03-12	2004-11-04	Jaemoon Lee	Preparation of 2-aminomethyl-5-fluorobenzamides
WO2004101512A2 (en)	2003-05-13	2004-11-25	Smithkline Beecham Corporation	Naphthyridine integrase inhibitors
CA2532064A1 (en) *	2003-07-15	2005-02-03	Merck & Co., Inc.	Hydroxypyridine cgrp receptor antagonists
TW200510425A (en)	2003-08-13	2005-03-16	Japan Tobacco Inc	Nitrogen-containing fused ring compound and use thereof as HIV integrase inhibitor
WO2005028478A1 (en)	2003-09-19	2005-03-31	Gilead Sciences, Inc.	Aza-quinolinol phosphonate integrase inhibitor compounds
JP2007509149A (ja)	2003-10-20	2007-04-12	メルク　エンド　カムパニー　インコーポレーテッド	Ｈｉｖインテグラーゼ阻害薬として有用なヒドロキシピリドピロロピラジンジオン化合物
TW200533357A (en)	2004-01-08	2005-10-16	Millennium Pharm Inc	2-(amino-substituted)-4-aryl pyrimidines and related compounds useful for treating inflammatory diseases
CA2554120A1 (en) *	2004-01-30	2005-08-18	Merck & Co., Inc.	N-benzyl-3,4-dihydroxypyridine-2-carboxamide and n-benzyl-2,3-dihydroxypyridine-4-carboxamide compounds useful as hiv integras inhibitors
EP1714966A4 (en) *	2004-02-04	2008-01-02	Shionogi & Co	NAPHTHYLIDINE DERIVATIVE HAVING HIGH INTEGRASE HIV INHIBITING ACTIVITY
EP1720856B1 (en)	2004-02-11	2013-08-14	GlaxoSmithKline LLC	Hiv integrase inhibitors
EP1725556A1 (en) *	2004-03-09	2006-11-29	Merck & Co., Inc.	Hiv integrase inhibitors
JP2007528396A (ja) *	2004-03-09	2007-10-11	メルク　エンド　カムパニー　インコーポレーテッド	Ｈｉｖインテグラーゼ阻害薬
JP2007528394A (ja) *	2004-03-09	2007-10-11	メルク　エンド　カムパニー　インコーポレーテッド	Ｈｉｖインテグラーゼ阻害薬
CA2557926A1 (en)	2004-03-09	2005-09-22	Monica Donghi	Hiv integrase inhibitors
EP1756114B1 (en) *	2004-05-07	2014-11-19	Merck Sharp & Dohme Corp.	Hiv integrase inhibitors
WO2005120516A2 (en) *	2004-06-09	2005-12-22	Merck & Co., Inc.	Hiv integrase inhibitors
UA87884C2 (uk)	2004-12-03	2009-08-25	Мерк Энд Ко., Инк.	Безводна кристалічна калієва сіль інгібітора віл-інтегрази
MX2007006637A (es) *	2004-12-03	2007-06-19	Merck & Co Inc	Uso de atazanavir para mejorar los parametros farmacocineticos de farmacos metabolizados por isoforma 1a1 de udp-glucuronosil- transferasa.
ATE516026T1 (de) *	2005-02-21	2011-07-15	Shionogi & Co	Bicyclisches carbamoylpyridonderivat mit hiv- integrase-hemmender wirkung
AU2006228278C1 (en) *	2005-03-31	2011-06-23	Msd Italia S.R.L.	HIV integrase inhibitors
CA2607151C (en) *	2005-05-10	2012-06-19	Merck & Co., Inc.	Hiv integrase inhibitors
EP1888581A2 (en) *	2005-05-16	2008-02-20	Gilead Sciences, Inc.	Hiv-integrase inhibitor compounds
WO2007019130A2 (en) *	2005-08-04	2007-02-15	Smithkline Beecham Corporation	Hiv integrase inhibitors
JP2009503083A (ja) *	2005-08-04	2009-01-29	スミスクラインビーチャムコーポレーション	Ｈｉｖインテグラーゼ阻害薬
US20080194523A1 (en) *	2005-08-04	2008-08-14	Smithkline Beecham Corporation	Hiv Integrase Inhibitors
EP1910363A4 (en) *	2005-08-04	2010-05-26	Glaxosmithkline Llc	INHIBITORS OF HIV INTEGRASE
CA2622639C (en) *	2005-10-04	2012-01-03	Istituto Di Recerche Di Biologia Molecolare P. Angeletti S.P.A.	Hiv integrase inhibitors
AU2006307101A1 (en)	2005-10-27	2007-05-03	Shionogi & Co., Ltd.	Polycyclic carbamoylpyridone derivative having inhibitory activity on HIV integrase
AU2006306355A1 (en) *	2005-10-27	2007-05-03	Merck & Co., Inc.	HIV integrase inhibitors
CN102702194A (zh) *	2005-12-21	2012-10-03	雅培制药有限公司	抗病毒化合物
WO2007136714A2 (en) *	2006-05-16	2007-11-29	Gilead Sciences, Inc.	Integrase inhibitors
CA2657287A1 (en) *	2006-07-17	2008-01-24	Merck & Co., Inc.	1-hydroxy naphthyridine compounds as anti-hiv agents
CA2658793A1 (en) *	2006-07-25	2008-02-07	Daniel Dumas	Quinoline derivatives
CN101522609A (zh) *	2006-09-05	2009-09-02	彼帕科学公司	癌症的治疗
ES2488922T3 (es)	2006-09-29	2014-09-01	Idenix Pharmaceuticals, Inc.	Fosfoindoles enantiómeramente puros como inhibidores del HIV
AU2007313293A1 (en) *	2006-10-18	2008-04-24	Merck & Co., Inc.	HIV integrase inhibitors
US20090291921A1 (en) *	2007-11-20	2009-11-26	Gilead Sciences, Inc.	Integrase inhibitors
CN101977610B (zh)	2008-01-25	2012-05-16	奇默里克斯公司	治疗病毒感染的方法
CA2730890C (en)	2008-07-17	2018-05-15	Critical Outcome Technologies Inc.	Thiosemicarbazone inhibitor compounds and cancer treatment methods
JP2012513464A (ja)	2008-12-23	2012-06-14	ザトラスティーズオブコロンビアユニヴァーシティインザシティオブニューヨーク	ホスホジエステラーゼ阻害剤及びその使用
JP2012528160A (ja)	2009-05-27	2012-11-12	メルク・シャープ・エンド・ドーム・コーポレイション	Ｈｉｖプロテアーゼ阻害薬
JP5624148B2 (ja) *	2009-10-13	2014-11-12	エランコ・アニマル・ヘルス・アイルランド・リミテッド	大環状インテグラーゼ阻害剤
ES2898348T3 (es)	2009-10-26	2022-03-07	Merck Sharp & Dohme	Composiciones farmacéuticas sólidas que contienen un inhibidor de la integrasa
EP2345643A1 (en)	2009-12-29	2011-07-20	Polichem S.A.	New tertiary 8-hydroxyquinoline-7-carboxamide derivatives and uses thereof
EP2345641A1 (en)	2009-12-29	2011-07-20	Polichem S.A.	New secondary 8-hydroxyquinoline-7-carboxamide derivatives
EP2345642A1 (en) *	2009-12-29	2011-07-20	Polichem S.A.	Secondary 8-hydroxyquinoline-7-carboxamide derivatives for use as antifungal agents
PT2534150T (pt)	2010-02-12	2017-05-02	Chimerix Inc	Métodos para tratar uma infecção viral
CA2794952C (en)	2010-04-01	2018-05-15	Critical Outcome Technologies Inc.	Compounds and method for treatment of hiv
RU2567385C2 (ru)	2010-04-02	2015-11-10	ЯНССЕН Ар ЭНД Ди АЙРЛЭНД	Макроциклические ингибиторы интегразы
WO2012055031A1 (en)	2010-10-28	2012-05-03	Merck Canada Inc.	Hiv protease inhibitors
EP2661265B1 (en)	2010-12-23	2017-03-08	Merck Sharp & Dohme Corp.	Quinolines and aza-quinolines as crth2 receptor modulators
ES2635030T3 (es)	2010-12-23	2017-10-02	Merck Sharp & Dohme Corp.	Quinoxalinas y aza-quinoxalinas como moduladores del receptor CRTH2
EP2487176A1 (en) *	2011-02-14	2012-08-15	Elanco Animal Health Ireland Limited	Macrocyclic integrase inhibitors for use in the treatment of feline immunodeficiency virus
CN103547566B (zh)	2011-02-18	2017-05-31	阿萨纳生物科技有限责任公司	氨基茚满化合物及其治疗疼痛的用途
EP2771332B1 (en)	2011-10-26	2016-06-29	Merck Canada Inc.	Thiophen and thiazol sulfonamid derivatives as HIV protease inhibitors for the treatment of AIDS
TWI603957B (zh)	2012-08-15	2017-11-01	阿沙納生物科學有限責任公司	胺基氫茚化合物用於治療膀胱過動症及間質性膀胱炎之用途
BR112015005347A2 (pt)	2012-09-11	2017-08-08	Merck Sharp & Dohme Corp E Merck Canada Inc	composto, composição farmacêutica, e, método para tratamento ou profilaxia de infecção por hiv ou para tratamento, profilaxia, ou atraso no início de aids
CN103709162B (zh) *	2012-09-29	2016-12-07	中国科学院上海药物研究所	三取代咪唑并二氮杂萘酮化合物及其制备方法和用途
CN104003986B (zh) *	2013-02-22	2016-06-08	中国科学院上海药物研究所	吡啶骈环类化合物及其制备方法、其药物组合物和用途
WO2015013835A1 (en)	2013-07-31	2015-02-05	Merck Sharp & Dohme Corp.	Piperazine derivatives as hiv protease inhibitors
WO2015095265A1 (en)	2013-12-19	2015-06-25	Merck Sharp & Dohme Corp.	Hiv protease inhibitors
WO2015095276A1 (en)	2013-12-19	2015-06-25	Merck Sharp & Dohme Corp.	Hiv protease inhibitors
WO2015134366A1 (en)	2014-03-06	2015-09-11	Merck Sharp & Dohme Corp.	Hiv protease inhibitors
US10138255B2 (en)	2014-03-10	2018-11-27	Merck Sharp & Dohme Corp.	Piperazine derivatives as HIV protease inhibitors
WO2017151922A1 (en)	2016-03-02	2017-09-08	The Board Of Regents Of The University Of Texas System	Sting activating nanovaccine for immunotherapy
CN106588922B (zh) *	2017-01-17	2018-04-27	北京工业大学	二取代八氢-1,6-萘啶类化合物及其制备方法和应用
WO2019018354A1 (en) *	2017-07-18	2019-01-24	Merck Patent Gmbh	ANTAGONISTS OF TLR7 / 8 AND USES THEREOF
CN109776415B (zh) *	2019-03-07	2020-11-17	福建南方制药股份有限公司	一种Roxadustat中间体的制备方法
CN115710249B (zh) *	2022-11-14	2024-11-19	广东工业大学	一种多取代异喹啉和1,6-萘啶化合物的制备方法及光电材料常见分子骨架
CN119841471B (zh) *	2025-03-24	2025-06-03	杭州汇能实业有限公司	一种热镀锌冷却循环水的处理方法

Family Cites Families (30)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS5751837B2 (cs) *	1973-04-05	1982-11-04
US4416884A (en)	1978-04-12	1983-11-22	Otsuka Pharmaceutical Co., Ltd.	Piperazinylbenzoheterocyclic compounds
FR2632639B1 (fr)	1988-06-09	1990-10-05	Sanofi Sa	Derives d'amino-4 carboxy-3 naphtyridines, leur preparation et compositions pharmaceutiques qui les contiennent
IL101860A0 (en)	1991-05-31	1992-12-30	Ici Plc	Heterocyclic derivatives
US5681832A (en) *	1995-02-17	1997-10-28	The United States Of America As Represented By The Department Of Health And Human Services	Aroylaniline compounds, pharmaceutical compositions, and methods of using same to inhibit viral activity
US5633362A (en) *	1995-05-12	1997-05-27	E. I. Du Pont De Nemours And Company	Production of 1,3-propanediol from glycerol by recombinant bacteria expressing recombinant diol dehydratase
ES2211965T3 (es) *	1995-08-02	2004-07-16	Darwin Discovery Limited	Quinolonas y su utilizacion terapeutica.
US5945431A (en)	1996-03-15	1999-08-31	Biochem Therapeutics Incorporated	Cytomegalovirus inhibiting compounds
US6310211B1 (en) *	1996-09-10	2001-10-30	Pharmacia & Upjohn Company	8-hydroxy-7-substituted quinolines as anti-viral agents
AU733551B2 (en)	1996-09-25	2001-05-17	Astrazeneca Ab	Qinoline derivatives inhibiting the effect of growth factors such as VEGF
US5766944A (en) *	1996-12-31	1998-06-16	Ruiz; Margaret Eileen	T cell differentiation of CD34+ stem cells in cultured thymic epithelial fragments
CA2295309A1 (en)	1997-06-30	1999-01-07	Nippon Kayaku Kabushiki Kaisha	Novel naphthyridine derivatives or salts thereof
YU10500A (sh)	1997-08-25	2002-10-18	Neurogen Corporation	Supstituisani 4-okso-naptiridin-3-karboksamidi kao gaba moždani receptorski liganidi
GB9720052D0 (en)	1997-09-19	1997-11-19	Smithkline Beecham Plc	Novel compounds
US6525042B1 (en)	1997-09-30	2003-02-25	Daiichi Pharmaceutical Co., Ltd.	Sulfonyl derivatives
RU2220960C2 (ru)	1997-12-22	2004-01-10	Фармация Энд Апджон Компани	4-гидрокси-3-хинолинкарбоксамиды и гидразиды, фармацевтическая композиция и способ лечения на их основе
US6306891B1 (en)	1998-06-03	2001-10-23	Merck & Co., Inc.	HIV integrase inhibitors
US6262055B1 (en)	1998-06-03	2001-07-17	Merck & Co., Inc.	HIV integrase inhibitors
US6380249B1 (en)	1998-06-03	2002-04-30	Merck & Co., Inc.	HIV integrase inhibitors
SE9802550D0 (sv)	1998-07-15	1998-07-15	Active Biotech Ab	Quinoline derivatives
JP2003503386A (ja)	1999-06-25	2003-01-28	メルクエンドカムパニーインコーポレーテッド	１−（芳香族またはヘテロ芳香族置換）−３−（ヘテロ芳香族置換）−１，３−プロパンジオン類およびそれの使用
US6730682B2 (en)	2000-07-12	2004-05-04	Pharmacia & Upjohn Company	Heterocycle carboxamides as antiviral agents
GB0017676D0 (en)	2000-07-19	2000-09-06	Angeletti P Ist Richerche Bio	Inhibitors of viral polymerase
ATE430745T1 (de) *	2000-10-12	2009-05-15	Merck & Co Inc	Aza- und polyaza naphthalenyl karboxamide als inhibitoren der hiv-integrase
CN1336363A (zh)	2001-07-25	2002-02-20	张元宾	乙酰磺胺酸钾的合成制备方法
AR036256A1 (es) *	2001-08-17	2004-08-25	Merck & Co Inc	Sal sodica de un inhibidor de integrasa del vih, procesos para su preparacion, composiciones farmaceuticas que lo contienen y su uso para la manufactura de un medicamento
EP1427726A1 (en)	2001-08-17	2004-06-16	Merck & Co., Inc.	Process for preparing 5-sulfonamido-8-hydroxy-1, 6-naphthyridine-7-carboxamides
DE60209381T2 (de)	2001-10-26	2006-10-05	Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A.	N-substituierte hydroxypyrimidinoncarboxamid-hemmer der hiv-integrase
SI1441734T1 (sl)	2001-10-26	2007-08-31	Angeletti P Ist Richerche Bio	Dihidropirimidin karboksamidni inhibitorji HIV-integraze
US20050165000A1 (en) *	2002-04-10	2005-07-28	Robertson Sandra K.	Pharmaceutical compositions containing an hiv integrase inhibitor and a nonionic surfactant

2001
- 2001-10-09 AT AT01979582T patent/ATE430745T1/de not_active IP Right Cessation
- 2001-10-09 AU AU1152702A patent/AU1152702A/xx active Pending
- 2001-10-09 KR KR10-2003-7005140A patent/KR20030036922A/ko not_active Withdrawn
- 2001-10-09 EP EP01979582A patent/EP1326865B1/en not_active Expired - Lifetime
- 2001-10-09 DE DE60138635T patent/DE60138635D1/de not_active Expired - Lifetime
- 2001-10-09 PL PL01360944A patent/PL360944A1/xx not_active Application Discontinuation
- 2001-10-09 CN CNA018172970A patent/CN1469878A/zh active Pending
- 2001-10-09 WO PCT/US2001/042564 patent/WO2002030931A2/en not_active Ceased
- 2001-10-09 AU AU2002211527A patent/AU2002211527B2/en not_active Ceased
- 2001-10-09 EA EA200300449A patent/EA200300449A1/ru unknown
- 2001-10-09 SK SK432-2003A patent/SK4322003A3/sk unknown
- 2001-10-09 CA CA2425440A patent/CA2425440C/en not_active Expired - Fee Related
- 2001-10-09 IL IL15508901A patent/IL155089A0/xx unknown
- 2001-10-09 NZ NZ525088A patent/NZ525088A/en unknown
- 2001-10-09 AU AU2002211874A patent/AU2002211874A1/en not_active Abandoned
- 2001-10-09 WO PCT/US2001/031456 patent/WO2002030930A2/en not_active Ceased
- 2001-10-09 MX MXPA03003263A patent/MXPA03003263A/es unknown
- 2001-10-09 CZ CZ20031028A patent/CZ20031028A3/cs unknown
- 2001-10-09 BR BR0114610-6A patent/BR0114610A/pt not_active IP Right Cessation
- 2001-10-09 EE EEP200300145A patent/EE200300145A/xx unknown
- 2001-10-09 HU HU0302367A patent/HUP0302367A2/hu unknown
- 2001-10-09 YU YU27903A patent/YU27903A/sh unknown
- 2001-10-09 JP JP2002534317A patent/JP4252797B2/ja not_active Expired - Fee Related
- 2001-10-10 US US09/973,853 patent/US6921759B2/en not_active Expired - Fee Related
- 2001-10-11 AR ARP010104777A patent/AR033845A1/es not_active Application Discontinuation
- 2001-10-11 PE PE2001001008A patent/PE20020509A1/es not_active Application Discontinuation
2003
- 2003-03-26 BG BG107677A patent/BG107677A/bg unknown
- 2003-03-27 IS IS6760A patent/IS6760A/is unknown
- 2003-04-11 NO NO20031672A patent/NO20031672L/no not_active Application Discontinuation
2005
- 2005-02-11 US US11/056,412 patent/US20050176718A1/en not_active Abandoned

Also Published As

Publication number	Publication date
BR0114610A (pt)	2005-12-13
BG107677A (bg)	2003-11-28
US20030055071A1 (en)	2003-03-20
CN1469878A (zh)	2004-01-21
KR20030036922A (ko)	2003-05-09
EE200300145A (et)	2003-06-16
CZ20031028A3 (cs)	2003-08-13
US20050176718A1 (en)	2005-08-11
WO2002030930A3 (en)	2002-08-29
AU2002211874A1 (en)	2002-04-22
PL360944A1 (en)	2004-09-20
AR033845A1 (es)	2004-01-07
CA2425440A1 (en)	2002-04-18
JP4252797B2 (ja)	2009-04-08
WO2002030931A3 (en)	2002-10-24
EA200300449A1 (ru)	2003-10-30
NO20031672D0 (no)	2003-04-11
YU27903A (sh)	2006-05-25
IL155089A0 (en)	2003-10-31
WO2002030930A2 (en)	2002-04-18
DE60138635D1 (de)	2009-06-18
WO2002030931A2 (en)	2002-04-18
HUP0302367A2 (hu)	2003-11-28
NZ525088A (en)	2004-11-26
CA2425440C (en)	2010-04-13
PE20020509A1 (es)	2002-06-20
ATE430745T1 (de)	2009-05-15
JP2004511483A (ja)	2004-04-15
NO20031672L (no)	2003-06-05
EP1326865B1 (en)	2009-05-06
US6921759B2 (en)	2005-07-26
AU1152702A (en)	2002-04-22
IS6760A (is)	2003-03-27
MXPA03003263A (es)	2003-06-06
EP1326865A2 (en)	2003-07-16
AU2002211527B2 (en)	2006-08-24

Legal Events

Date	Code	Title	Description
2010-05-07	FB9A	Suspension of patent application procedure

Publication	Publication Date	Title
JP4252797B2 (ja)	2009-04-08	Ｈｉｖインテグラーゼ阻害薬として有用なアザ−およびポリアザ−ナフタレニルカルボキサミド類
JP4287649B2 (ja)	2009-07-01	Ｈｉｖインテグラーゼ阻害薬として有用なアザ−およびポリアザ−ナフタレニルカルボキサミド類
CN114728962B (zh)	2025-09-19	血浆激肽释放酶抑制剂及其用途
TWI399380B (zh)	2013-06-21	抗病毒化合物
KR101689421B1 (ko)	2016-12-23	치환된 이미다조피리디닐-아미노피리딘 화합물
CN102939289B (zh)	2016-01-20	取代的5-氟-1h-吡唑并吡啶类化合物及其用途
ES2274913T3 (es)	2007-06-01	Aza y poliaza-naftalenil carboxamidas utiles como inhibidores de vih integrada.
JP4523281B2 (ja)	2010-08-11	Ｈｉｖインテグラーゼ阻害薬として有用なヒドロキシナフチリジノンカルボキサミド類
JP7269917B2 (ja)	2023-05-09	Ａｈｒ阻害剤およびその使用
WO2018157857A1 (zh)	2018-09-07	凋亡信号调节激酶抑制剂及其制备方法和应用
AU2003292436A1 (en)	2004-07-22	Tetrahydro-4H-pyrido[1,2-A]pyrimidines and related compounds useful as HIV integrase inhibitors
AU2002211527A1 (en)	2002-06-27	Aza- and polyaza-naphthalenyl carboxamides useful as HIV integrase inhibitors
KR20090106604A (ko)	2009-10-09	축합 피리딘 화합물
TWI783205B (zh)	2022-11-11	鹵代烯丙基胺類化合物及其用途
AU2002215328A1 (en)	2002-06-27	AZA- and polyaza-naphthalenyl-carboxamides useful as HIV integrase inhibitors
SK57893A3 (en)	1994-01-12	Imidazopyridine derivatives, process for their preparation and pharmaceutical compositions
WO2005019188A1 (ja)	2005-03-03	縮合ピリミジン誘導体およびその用途
RS63656B1 (sr)	2022-11-30	Kondenzovano heterociklično jedinjenje
CN107074856A (zh)	2017-08-18	CaMKII抑制剂及其用途
CN101005843A (zh)	2007-07-25	吡咯并三嗪激酶抑制剂
JP2004115450A (ja)	2004-04-15	医薬組成物
HK1062299A (en)	2004-10-29	Aza- and polyaza-naphthalenyl carboxamides useful as hiv integrase inhibitors
HK40053245A (en)	2022-02-04	Haloallylamine compounds and application thereof
HK40053245B (en)	2025-04-17	Haloallylamine compounds and application thereof