OA12161A - PyridoÄ2,3-dÜpyrimidine-2,7-diamine kinase inhibitors. - Google Patents

PyridoÄ2,3-dÜpyrimidine-2,7-diamine kinase inhibitors. Download PDF

Info

Publication number: OA12161A
Authority: OA; OAPI
Prior art keywords: pyrido; pyrimidin; urea; piperazin; phenylamino
Prior art date: 2000-01-25

Application number

OA1200200213A

Other languages

English (en)

Inventor

Richard John Booth

Ellen Myra Dobrusin

Vara Prasad Venkata Na Josyula

Dennis Joseph Mcnamara

Peter Laurence Toogood

Original Assignee

Warner Lambert Co

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

2000-01-25

Filing date

2001-01-23

Publication date

2006-05-08

2001-01-23 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

2006-05-08 Publication of OA12161A publication Critical patent/OA12161A/en

Links

229940043355 kinase inhibitor Drugs 0.000 title description 2
239000003757 phosphotransferase inhibitor Substances 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 135
125000000217 alkyl group Chemical group 0.000 claims abstract description 55
229910052736 halogen Inorganic materials 0.000 claims abstract description 34
150000002367 halogens Chemical class 0.000 claims abstract description 30
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 26
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 23
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 22
206010028980 Neoplasm Diseases 0.000 claims abstract description 19
125000003118 aryl group Chemical group 0.000 claims abstract description 19
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
239000001257 hydrogen Substances 0.000 claims abstract description 17
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 17
201000011510 cancer Diseases 0.000 claims abstract description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 12
125000003342 alkenyl group Chemical group 0.000 claims abstract description 12
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 12
125000000304 alkynyl group Chemical group 0.000 claims abstract description 11
239000003102 growth factor Substances 0.000 claims abstract description 11
230000001404 mediated effect Effects 0.000 claims abstract description 9
208000037803 restenosis Diseases 0.000 claims abstract description 6
125000000753 cycloalkyl group Chemical group 0.000 claims abstract 4
239000004202 carbamide Substances 0.000 claims description 90
150000002148 esters Chemical class 0.000 claims description 40
-1 nitro, carboxy Chemical group 0.000 claims description 40
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 23
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
125000003545 alkoxy group Chemical group 0.000 claims description 20
150000003839 salts Chemical class 0.000 claims description 17
101150073031 cdk2 gene Proteins 0.000 claims description 16
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
102000004190 Enzymes Human genes 0.000 claims description 13
108090000790 Enzymes Proteins 0.000 claims description 13
102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 13
108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 13
150000001408 amides Chemical class 0.000 claims description 13
229910052757 nitrogen Inorganic materials 0.000 claims description 12
239000000651 prodrug Substances 0.000 claims description 10
229940002612 prodrug Drugs 0.000 claims description 10
125000002837 carbocyclic group Chemical group 0.000 claims description 9
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
201000010099 disease Diseases 0.000 claims description 8
208000035475 disorder Diseases 0.000 claims description 8
230000002401 inhibitory effect Effects 0.000 claims description 8
101100005789 Caenorhabditis elegans cdk-4 gene Proteins 0.000 claims description 7
125000003710 aryl alkyl group Chemical group 0.000 claims description 7
125000004663 dialkyl amino group Chemical group 0.000 claims description 7
125000005842 heteroatom Chemical group 0.000 claims description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 6
229910052760 oxygen Inorganic materials 0.000 claims description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
201000004681 Psoriasis Diseases 0.000 claims description 5
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
210000001072 colon Anatomy 0.000 claims description 3
125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
241000124008 Mammalia Species 0.000 claims description 2
229910052799 carbon Inorganic materials 0.000 claims description 2
AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 claims description 2
210000004072 lung Anatomy 0.000 claims description 2
201000001441 melanoma Diseases 0.000 claims description 2
210000000329 smooth muscle myocyte Anatomy 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 7
238000004519 manufacturing process Methods 0.000 claims 6
125000004181 carboxyalkyl group Chemical group 0.000 claims 2
125000005143 heteroarylsulfonyl group Chemical group 0.000 claims 2
DMQGWXYTVMVWCU-UHFFFAOYSA-N 1-tert-butyl-3-[5-methyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C=C2C(C)=CC(NC(=O)NC(C)(C)C)=NC2=NC=1NC(C=C1)=CC=C1N1CCNCC1 DMQGWXYTVMVWCU-UHFFFAOYSA-N 0.000 claims 1
206010057469 Vascular stenosis Diseases 0.000 claims 1
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 1
208000003849 large cell carcinoma Diseases 0.000 claims 1
210000002464 muscle smooth vascular Anatomy 0.000 claims 1
108091000080 Phosphotransferase Proteins 0.000 abstract description 11
102000020233 phosphotransferase Human genes 0.000 abstract description 11
239000003112 inhibitor Substances 0.000 abstract description 9
230000003389 potentiating effect Effects 0.000 abstract description 7
239000008194 pharmaceutical composition Substances 0.000 abstract description 4
150000002431 hydrogen Chemical class 0.000 abstract description 2
230000002062 proliferating effect Effects 0.000 abstract description 2
239000000047 product Substances 0.000 description 173
239000007787 solid Substances 0.000 description 114
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
239000000243 solution Substances 0.000 description 40
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 28
238000000034 method Methods 0.000 description 28
239000000460 chlorine Substances 0.000 description 27
239000000725 suspension Substances 0.000 description 27
238000006243 chemical reaction Methods 0.000 description 24
239000000203 mixture Substances 0.000 description 20
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 19
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 19
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 17
FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 16
210000004027 cell Anatomy 0.000 description 14
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 13
XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 13
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 11
239000002253 acid Substances 0.000 description 11
238000001914 filtration Methods 0.000 description 11
230000005764 inhibitory process Effects 0.000 description 11
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
229910000041 hydrogen chloride Inorganic materials 0.000 description 10
WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical group NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 9
235000013877 carbamide Nutrition 0.000 description 9
230000000694 effects Effects 0.000 description 9
239000003826 tablet Substances 0.000 description 9
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
238000003556 assay Methods 0.000 description 8
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 8
229920002472 Starch Polymers 0.000 description 7
230000015572 biosynthetic process Effects 0.000 description 7
230000022131 cell cycle Effects 0.000 description 7
239000003795 chemical substances by application Substances 0.000 description 7
239000000463 material Substances 0.000 description 7
239000011734 sodium Substances 0.000 description 7
229910052708 sodium Inorganic materials 0.000 description 7
239000008107 starch Substances 0.000 description 7
235000019698 starch Nutrition 0.000 description 7
239000007858 starting material Substances 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
102000001332 SRC Human genes 0.000 description 6
108060006706 SRC Proteins 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000000872 buffer Substances 0.000 description 6
239000002775 capsule Substances 0.000 description 6
239000002552 dosage form Substances 0.000 description 6
239000012948 isocyanate Substances 0.000 description 6
150000002513 isocyanates Chemical class 0.000 description 6
238000012360 testing method Methods 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
101150053721 Cdk5 gene Proteins 0.000 description 5
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 5
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
238000003818 flash chromatography Methods 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
239000001301 oxygen Substances 0.000 description 5
239000000843 powder Substances 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
JLJIEMWRJUNUFJ-UHFFFAOYSA-N tert-butyl 4-[4-[[7-(tert-butylcarbamoylamino)pyrido[2,3-d]pyrimidin-2-yl]amino]phenyl]piperazine-1-carboxylate Chemical compound N=1C2=NC(NC(=O)NC(C)(C)C)=CC=C2C=NC=1NC(C=C1)=CC=C1N1CCN(C(=O)OC(C)(C)C)CC1 JLJIEMWRJUNUFJ-UHFFFAOYSA-N 0.000 description 5
PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 4
201000001320 Atherosclerosis Diseases 0.000 description 4
102000016736 Cyclin Human genes 0.000 description 4
108050006400 Cyclin Proteins 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
241000238631 Hexapoda Species 0.000 description 4
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
101150093908 PDGFRB gene Proteins 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
241000206607 Porphyra umbilicalis Species 0.000 description 4
239000007983 Tris buffer Substances 0.000 description 4
241000700605 Viruses Species 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
239000002585 base Substances 0.000 description 4
239000011324 bead Substances 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
239000000796 flavoring agent Substances 0.000 description 4
125000004356 hydroxy functional group Chemical group O* 0.000 description 4
238000011534 incubation Methods 0.000 description 4
239000007788 liquid Substances 0.000 description 4
238000013508 migration Methods 0.000 description 4
230000005012 migration Effects 0.000 description 4
YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
BWESROVQGZSBRX-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine Chemical group C1=NC=NC2=CC=CN=C21 BWESROVQGZSBRX-UHFFFAOYSA-N 0.000 description 4
238000010992 reflux Methods 0.000 description 4
238000003756 stirring Methods 0.000 description 4
125000001424 substituent group Chemical group 0.000 description 4
239000000454 talc Substances 0.000 description 4
229910052623 talc Inorganic materials 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
MGOLNIXAPIAKFM-UHFFFAOYSA-N 2-isocyanato-2-methylpropane Chemical compound CC(C)(C)N=C=O MGOLNIXAPIAKFM-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
108020004414 DNA Proteins 0.000 description 3
206010012689 Diabetic retinopathy Diseases 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
108010033040 Histones Proteins 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
102000001253 Protein Kinase Human genes 0.000 description 3
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
102100022563 Tubulin polymerization-promoting protein Human genes 0.000 description 3
NIXOWILDQLNWCW-UHFFFAOYSA-M acrylate group Chemical group C(C=C)(=O)[O-] NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 3
235000019270 ammonium chloride Nutrition 0.000 description 3
210000000481 breast Anatomy 0.000 description 3
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
239000000969 carrier Substances 0.000 description 3
230000001413 cellular effect Effects 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
229940125797 compound 12 Drugs 0.000 description 3
229960004132 diethyl ether Drugs 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
239000003937 drug carrier Substances 0.000 description 3
235000019634 flavors Nutrition 0.000 description 3
238000010348 incorporation Methods 0.000 description 3
238000000021 kinase assay Methods 0.000 description 3
239000006166 lysate Substances 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
108060006633 protein kinase Proteins 0.000 description 3
102000004169 proteins and genes Human genes 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
UDJFFSGCRRMVFH-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine Chemical class N1=CN=CC2=CC=CN=C21 UDJFFSGCRRMVFH-UHFFFAOYSA-N 0.000 description 3
238000011160 research Methods 0.000 description 3
FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
229940048086 sodium pyrophosphate Drugs 0.000 description 3
239000000758 substrate Substances 0.000 description 3
239000011593 sulfur Substances 0.000 description 3
239000000829 suppository Substances 0.000 description 3
UYFBIPVOSCMPAT-UHFFFAOYSA-N tert-butyl 4-[4-[(7-aminopyrido[2,3-d]pyrimidin-2-yl)amino]phenyl]piperazine-1-carboxylate Chemical group C1CN(C(=O)OC(C)(C)C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=CC(N)=N2)C2=N1 UYFBIPVOSCMPAT-UHFFFAOYSA-N 0.000 description 3
235000019818 tetrasodium diphosphate Nutrition 0.000 description 3
239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 3
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
239000001993 wax Substances 0.000 description 3
VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 2
WPUAPGRZGJOIBX-UHFFFAOYSA-N 2-methylsulfanyl-8h-pyrido[2,3-d]pyrimidin-7-one Chemical compound C1=CC(=O)NC2=NC(SC)=NC=C21 WPUAPGRZGJOIBX-UHFFFAOYSA-N 0.000 description 2
GBTYIAXFRCTFAA-UHFFFAOYSA-N 2-methylsulfinylpyrido[2,3-d]pyrimidin-7-amine Chemical compound C1=CC(N)=NC2=NC(S(=O)C)=NC=C21 GBTYIAXFRCTFAA-UHFFFAOYSA-N 0.000 description 2
YIAMBFRNQLHKKR-UHFFFAOYSA-N 2-n-phenylpyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound N=1C2=NC(N)=CC=C2C=NC=1NC1=CC=CC=C1 YIAMBFRNQLHKKR-UHFFFAOYSA-N 0.000 description 2
QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 2
WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 2
WAKWFGNVQUBSFC-UHFFFAOYSA-N 4-[4-[[7-(tert-butylcarbamoylamino)pyrido[2,3-d]pyrimidin-2-yl]amino]phenyl]piperazine-1-carboxylic acid Chemical compound N=1C2=NC(NC(=O)NC(C)(C)C)=CC=C2C=NC=1NC(C=C1)=CC=C1N1CCN(C(O)=O)CC1 WAKWFGNVQUBSFC-UHFFFAOYSA-N 0.000 description 2
KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 2
BSKBDNXMRMMXLQ-UHFFFAOYSA-N 6-fluoro-2-methylsulfanylpyrido[2,3-d]pyrimidin-7-amine Chemical compound C1=C(F)C(N)=NC2=NC(SC)=NC=C21 BSKBDNXMRMMXLQ-UHFFFAOYSA-N 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical class CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
206010006187 Breast cancer Diseases 0.000 description 2
208000026310 Breast neoplasm Diseases 0.000 description 2
201000009030 Carcinoma Diseases 0.000 description 2
206010011416 Croup infectious Diseases 0.000 description 2
102000003903 Cyclin-dependent kinases Human genes 0.000 description 2
108090000266 Cyclin-dependent kinases Proteins 0.000 description 2
241000514744 Cyclina Species 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
102000009465 Growth Factor Receptors Human genes 0.000 description 2
108010009202 Growth Factor Receptors Proteins 0.000 description 2
XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 2
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical group ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
102100031167 Tyrosine-protein kinase CSK Human genes 0.000 description 2
101710086605 Tyrosine-protein kinase CSK Proteins 0.000 description 2
208000036142 Viral infection Diseases 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
125000005907 alkyl ester group Chemical group 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
230000033115 angiogenesis Effects 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
239000012267 brine Substances 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
229940110456 cocoa butter Drugs 0.000 description 2
235000019868 cocoa butter Nutrition 0.000 description 2
239000003086 colorant Substances 0.000 description 2
229940125904 compound 1 Drugs 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
201000010549 croup Diseases 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
239000012971 dimethylpiperazine Substances 0.000 description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
239000003814 drug Substances 0.000 description 2
238000009472 formulation Methods 0.000 description 2
125000000524 functional group Chemical group 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
239000008187 granular material Substances 0.000 description 2
JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
208000032839 leukemia Diseases 0.000 description 2
239000007937 lozenge Substances 0.000 description 2
208000020816 lung neoplasm Diseases 0.000 description 2
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
238000002156 mixing Methods 0.000 description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
229910000069 nitrogen hydride Inorganic materials 0.000 description 2
102000037979 non-receptor tyrosine kinases Human genes 0.000 description 2
108091008046 non-receptor tyrosine kinases Proteins 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
230000003204 osmotic effect Effects 0.000 description 2
210000003800 pharynx Anatomy 0.000 description 2
JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
239000006187 pill Substances 0.000 description 2
RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
230000008569 process Effects 0.000 description 2
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
210000002307 prostate Anatomy 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
230000000717 retained effect Effects 0.000 description 2
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
229940081974 saccharin Drugs 0.000 description 2
235000019204 saccharin Nutrition 0.000 description 2
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 2
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
239000004299 sodium benzoate Substances 0.000 description 2
235000010234 sodium benzoate Nutrition 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
235000011121 sodium hydroxide Nutrition 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
239000002904 solvent Substances 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
238000012289 standard assay Methods 0.000 description 2
210000002784 stomach Anatomy 0.000 description 2
125000003107 substituted aryl group Chemical group 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
QUKABSSPBMVPRN-UHFFFAOYSA-N tert-butyl 4-(4-aminophenyl)-2,2-dimethylpiperazine-1-carboxylate Chemical compound C1C(C)(C)N(C(=O)OC(C)(C)C)CCN1C1=CC=C(N)C=C1 QUKABSSPBMVPRN-UHFFFAOYSA-N 0.000 description 2
RXFHRKPNLPBDGE-UHFFFAOYSA-N tert-butyl 4-(4-aminophenyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(N)C=C1 RXFHRKPNLPBDGE-UHFFFAOYSA-N 0.000 description 2
QRWVTEIEDYKPMU-UHFFFAOYSA-N tert-butyl 4-[4-[[7-(cyclopentylcarbamoylamino)pyrido[2,3-d]pyrimidin-2-yl]amino]phenyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=CC(NC(=O)NC2CCCC2)=N2)C2=N1 QRWVTEIEDYKPMU-UHFFFAOYSA-N 0.000 description 2
CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical group CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 2
239000002562 thickening agent Substances 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
241000701447 unidentified baculovirus Species 0.000 description 2
241001529453 unidentified herpesvirus Species 0.000 description 2
230000009385 viral infection Effects 0.000 description 2
VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 1
UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 1
SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
PTSOWWFWSWKGAE-IYBDPMFKSA-N (2S,6R)-4-[4-[[7-(tert-butylcarbamoylamino)pyrido[2,3-d]pyrimidin-2-yl]amino]phenyl]-2,6-dimethylpiperazine-1-carboxylic acid Chemical group C(C)(C)(C)NC(NC=1C=CC2=C(N=C(N=C2)NC2=CC=C(C=C2)N2C[C@@H](N([C@@H](C2)C)C(=O)O)C)N1)=O PTSOWWFWSWKGAE-IYBDPMFKSA-N 0.000 description 1
NWYYWIJOWOLJNR-YFKPBYRVSA-N (2r)-2-amino-3-methylbutan-1-ol Chemical group CC(C)[C@@H](N)CO NWYYWIJOWOLJNR-YFKPBYRVSA-N 0.000 description 1
GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 description 1
IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 1
YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 1
WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
VPSSPAXIFBTOHY-LURJTMIESA-N (2s)-2-amino-4-methylpentan-1-ol Chemical group CC(C)C[C@H](N)CO VPSSPAXIFBTOHY-LURJTMIESA-N 0.000 description 1
STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 1
QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
FNHHVPPSBFQMEL-KQHDFZBMSA-N (3S)-5-N-[(1S,5R)-3-hydroxy-6-bicyclo[3.1.0]hexanyl]-7-N,3-dimethyl-3-phenyl-2H-1-benzofuran-5,7-dicarboxamide Chemical compound CNC(=O)c1cc(cc2c1OC[C@@]2(C)c1ccccc1)C(=O)NC1[C@H]2CC(O)C[C@@H]12 FNHHVPPSBFQMEL-KQHDFZBMSA-N 0.000 description 1
IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 1
OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 description 1
HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 1
MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 1
XLVOWGDFXAVSFE-UHFFFAOYSA-N (4-amino-2-methylsulfanylpyrimidin-5-yl)methanol Chemical compound CSC1=NC=C(CO)C(N)=N1 XLVOWGDFXAVSFE-UHFFFAOYSA-N 0.000 description 1
YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 1
STPKWKPURVSAJF-LJEWAXOPSA-N (4r,5r)-5-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2h-1$l^{6}-benzothiepin-4-ol Chemical compound O[C@H]1C(CCCC)(CCCC)CS(=O)(=O)C2=CC=C(N(C)C)C=C2[C@H]1C(C=C1)=CC=C1OCC(C=C1)=CC=C1C[N+]1(CC2)CCN2CC1 STPKWKPURVSAJF-LJEWAXOPSA-N 0.000 description 1
ZLHKUOXVUSHCLN-UHFFFAOYSA-N (furan-2-ylmethylideneamino)thiourea Chemical compound NC(=S)NN=CC1=CC=CO1 ZLHKUOXVUSHCLN-UHFFFAOYSA-N 0.000 description 1
MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 1
DJMOXMNDXFFONV-UHFFFAOYSA-N 1,3-dimethyl-7-[2-(n-methylanilino)ethyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCN(C)C1=CC=CC=C1 DJMOXMNDXFFONV-UHFFFAOYSA-N 0.000 description 1
PAHKIBZRWFCOAM-UHFFFAOYSA-N 1-(2-hydroxyethyl)-3-[2-(pyridin-4-ylamino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C2=NC(NC(=O)NCCO)=CC=C2C=NC=1NC1=CC=NC=C1 PAHKIBZRWFCOAM-UHFFFAOYSA-N 0.000 description 1
XFILUMCRLWWGHF-UHFFFAOYSA-N 1-(2-hydroxyethyl)-3-[5-methyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C=C2C(C)=CC(NC(=O)NCCO)=NC2=NC=1NC(C=C1)=CC=C1N1CCNCC1 XFILUMCRLWWGHF-UHFFFAOYSA-N 0.000 description 1
RAQHINAQAPWZKV-UHFFFAOYSA-N 1-(4-amino-2-methylsulfinylpyrimidin-5-yl)ethanone Chemical group CC(=O)C1=CN=C(S(C)=O)N=C1N RAQHINAQAPWZKV-UHFFFAOYSA-N 0.000 description 1
VWOJSRICSKDKAW-UHFFFAOYSA-N 1-(4-nitrophenyl)piperazine Chemical compound C1=CC([N+](=O)[O-])=CC=C1N1CCNCC1 VWOJSRICSKDKAW-UHFFFAOYSA-N 0.000 description 1
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical group CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 1
WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
MQLDVUKGKUIAAL-UHFFFAOYSA-N 1-[5-methyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]-3-propan-2-ylurea Chemical compound N=1C2=NC(NC(=O)NC(C)C)=CC(C)=C2C=NC=1NC(C=C1)=CC=C1N1CCNCC1 MQLDVUKGKUIAAL-UHFFFAOYSA-N 0.000 description 1
ITGHYDKCLQIJEO-UHFFFAOYSA-N 1-[6-chloro-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]-3-cyclohexylurea Chemical compound N1=C2N=C(NC(=O)NC3CCCCC3)C(Cl)=CC2=CN=C1NC(C=C1)=CC=C1N1CCNCC1 ITGHYDKCLQIJEO-UHFFFAOYSA-N 0.000 description 1
PKJBWOWQJHHAHG-UHFFFAOYSA-N 1-bromo-4-phenylbenzene Chemical group C1=CC(Br)=CC=C1C1=CC=CC=C1 PKJBWOWQJHHAHG-UHFFFAOYSA-N 0.000 description 1
ADAKRBAJFHTIEW-UHFFFAOYSA-N 1-chloro-4-isocyanatobenzene Chemical group ClC1=CC=C(N=C=O)C=C1 ADAKRBAJFHTIEW-UHFFFAOYSA-N 0.000 description 1
MPBWULVFTHBBOK-UHFFFAOYSA-N 1-cyclohexyl-3-[5-methyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C2=NC(NC=3C=CC(=CC=3)N3CCNCC3)=NC=C2C(C)=CC=1NC(=O)NC1CCCCC1 MPBWULVFTHBBOK-UHFFFAOYSA-N 0.000 description 1
LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical compound CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 1
125000006052 1-methyl-3-pentenyl group Chemical group 0.000 description 1
WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 description 1
FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 description 1
VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 description 1
QEBYEVQKHRUYPE-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-[(1-methylpyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CN(C)N=C1CN1C(=O)C=C2NN(C=3C(=CC=CC=3)Cl)C(=O)C2=C1CN(C)CC1=CC=CN=C1 QEBYEVQKHRUYPE-UHFFFAOYSA-N 0.000 description 1
NLMKTBGFQGKQEV-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-hexadecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO NLMKTBGFQGKQEV-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 description 1
VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 description 1
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
ZTGBKXVQAMZVAI-UHFFFAOYSA-N 2-diethoxyphosphorylbutanenitrile Chemical compound CCOP(=O)(OCC)C(CC)C#N ZTGBKXVQAMZVAI-UHFFFAOYSA-N 0.000 description 1
GSLTVFIVJMCNBH-UHFFFAOYSA-N 2-isocyanatopropane Chemical group CC(C)N=C=O GSLTVFIVJMCNBH-UHFFFAOYSA-N 0.000 description 1
LFOIDLOIBZFWDO-UHFFFAOYSA-N 2-methoxy-6-[6-methoxy-4-[(3-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=C2SC(OC)=NN2C=C1C(OC1=CC(OC)=C2)=CC1=C2OCC(C=1)=CC=CC=1OCC1=CC=CC=C1 LFOIDLOIBZFWDO-UHFFFAOYSA-N 0.000 description 1
OXXHQZJBSKTBQV-UHFFFAOYSA-N 2-methylsulfanylpyrido[2,3-d]pyrimidin-7-amine Chemical compound C1=CC(N)=NC2=NC(SC)=NC=C21 OXXHQZJBSKTBQV-UHFFFAOYSA-N 0.000 description 1
BAWUPLMANDGIJL-UHFFFAOYSA-N 2-n-(4-fluoro-3-methylphenyl)pyrido[2,3-d]pyrimidine-2,7-diamine Chemical group C1=C(F)C(C)=CC(NC=2N=C3N=C(N)C=CC3=CN=2)=C1 BAWUPLMANDGIJL-UHFFFAOYSA-N 0.000 description 1
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
DEMNOIPKWUBEAZ-UHFFFAOYSA-N 2-pyrimidin-5-ylethanol Chemical compound OCCC1=CN=CN=C1 DEMNOIPKWUBEAZ-UHFFFAOYSA-N 0.000 description 1
LSMAJBKCYYJNCC-UHFFFAOYSA-N 3,3-dimethyl-1-(4-nitrophenyl)piperazine Chemical compound C1CNC(C)(C)CN1C1=CC=C([N+]([O-])=O)C=C1 LSMAJBKCYYJNCC-UHFFFAOYSA-N 0.000 description 1
DFRAKBCRUYUFNT-UHFFFAOYSA-N 3,8-dicyclohexyl-2,4,7,9-tetrahydro-[1,3]oxazino[5,6-h][1,3]benzoxazine Chemical compound C1CCCCC1N1CC(C=CC2=C3OCN(C2)C2CCCCC2)=C3OC1 DFRAKBCRUYUFNT-UHFFFAOYSA-N 0.000 description 1
HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
125000005925 3-methylpentyloxy group Chemical group 0.000 description 1
UIKUBYKUYUSRSM-UHFFFAOYSA-N 3-morpholinopropylamine Chemical compound NCCCN1CCOCC1 UIKUBYKUYUSRSM-UHFFFAOYSA-N 0.000 description 1
JWOVNYMWNOVOCI-UHFFFAOYSA-N 4-[4-[(7-aminopyrido[2,3-d]pyrimidin-2-yl)amino]phenyl]piperazine-1-carboxylic acid Chemical compound N=1C2=NC(N)=CC=C2C=NC=1NC(C=C1)=CC=C1N1CCN(C(O)=O)CC1 JWOVNYMWNOVOCI-UHFFFAOYSA-N 0.000 description 1
WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 1
MPMKMQHJHDHPBE-RUZDIDTESA-N 4-[[(2r)-1-(1-benzothiophene-3-carbonyl)-2-methylazetidine-2-carbonyl]-[(3-chlorophenyl)methyl]amino]butanoic acid Chemical compound O=C([C@@]1(N(CC1)C(=O)C=1C2=CC=CC=C2SC=1)C)N(CCCC(O)=O)CC1=CC=CC(Cl)=C1 MPMKMQHJHDHPBE-RUZDIDTESA-N 0.000 description 1
DQAZPZIYEOGZAF-UHFFFAOYSA-N 4-ethyl-n-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]piperazine-1-carboxamide Chemical compound C1CN(CC)CCN1C(=O)NC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=CC(C#C)=C1 DQAZPZIYEOGZAF-UHFFFAOYSA-N 0.000 description 1
NYMDPDNETOLVBS-UHFFFAOYSA-N 4-fluoro-3-methylaniline Chemical group CC1=CC(N)=CC=C1F NYMDPDNETOLVBS-UHFFFAOYSA-N 0.000 description 1
KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical group NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 1
VKLKXFOZNHEBSW-UHFFFAOYSA-N 5-[[3-[(4-morpholin-4-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide Chemical compound O1CCN(CC1)C1=CC=C(C(=O)NC=2C=C(COC=3C=NC=C(C(=O)N)C=3)C=CC=2)C=C1 VKLKXFOZNHEBSW-UHFFFAOYSA-N 0.000 description 1
XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 description 1
XJTBMLQVSGDVOT-UHFFFAOYSA-N 5-methyl-2-methylsulfinylpyrido[2,3-d]pyrimidin-7-amine Chemical group CS(=O)C1=NC=C2C(C)=CC(N)=NC2=N1 XJTBMLQVSGDVOT-UHFFFAOYSA-N 0.000 description 1
RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 description 1
KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
FEDCSLRPQNWUHW-UHFFFAOYSA-N 6-bromo-2-methylsulfanyl-8h-pyrido[2,3-d]pyrimidin-7-one Chemical compound C1=C(Br)C(=O)NC2=NC(SC)=NC=C21 FEDCSLRPQNWUHW-UHFFFAOYSA-N 0.000 description 1
GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 description 1
JWYVUHNTODXXRU-UHFFFAOYSA-N 6-chloro-2-methylsulfanylpyrido[2,3-d]pyrimidin-7-amine Chemical compound C1=C(Cl)C(N)=NC2=NC(SC)=NC=C21 JWYVUHNTODXXRU-UHFFFAOYSA-N 0.000 description 1
HEXUGCQBLSDFMP-UHFFFAOYSA-N 6-fluoro-2-methylsulfanyl-8h-pyrido[2,3-d]pyrimidin-7-one Chemical group C1=C(F)C(=O)NC2=NC(SC)=NC=C21 HEXUGCQBLSDFMP-UHFFFAOYSA-N 0.000 description 1
DWWCZKVBNWJJHC-UHFFFAOYSA-N 6-methoxy-2,3-dihydro-1h-indene-5-carbaldehyde Chemical compound C1=C(C=O)C(OC)=CC2=C1CCC2 DWWCZKVBNWJJHC-UHFFFAOYSA-N 0.000 description 1
KNLKKWMQDADZHW-UHFFFAOYSA-N 7-chloro-6-fluoro-2-methylsulfanylpyrido[2,3-d]pyrimidine Chemical compound C1=C(F)C(Cl)=NC2=NC(SC)=NC=C21 KNLKKWMQDADZHW-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-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
XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 description 1
208000003200 Adenoma Diseases 0.000 description 1
206010001233 Adenoma benign Diseases 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
108010039627 Aprotinin Proteins 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
241000201370 Autographa californica nucleopolyhedrovirus Species 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
IYHHRZBKXXKDDY-UHFFFAOYSA-N BI-605906 Chemical compound N=1C=2SC(C(N)=O)=C(N)C=2C(C(F)(F)CC)=CC=1N1CCC(S(C)(=O)=O)CC1 IYHHRZBKXXKDDY-UHFFFAOYSA-N 0.000 description 1
206010005003 Bladder cancer Diseases 0.000 description 1
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
241000167854 Bourreria succulenta Species 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 description 1
OJRUSAPKCPIVBY-KQYNXXCUSA-N C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N Chemical compound C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N OJRUSAPKCPIVBY-KQYNXXCUSA-N 0.000 description 1
BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 1
108091007914 CDKs Proteins 0.000 description 1
RSLFWIACPZZFIN-TXEJJXNPSA-N C[C@@H]1CN(C[C@@H](N1C(=O)O)C)C2=CC=C(C=C2)NC3=NC4=NC(=C(C=C4C=N3)F)N Chemical group C[C@@H]1CN(C[C@@H](N1C(=O)O)C)C2=CC=C(C=C2)NC3=NC4=NC(=C(C=C4C=N3)F)N RSLFWIACPZZFIN-TXEJJXNPSA-N 0.000 description 1
PKMUHQIDVVOXHQ-HXUWFJFHSA-N C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O Chemical compound C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O PKMUHQIDVVOXHQ-HXUWFJFHSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
208000010667 Carcinoma of liver and intrahepatic biliary tract Diseases 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
235000008733 Citrus aurantifolia Nutrition 0.000 description 1
108020004635 Complementary DNA Proteins 0.000 description 1
229940126657 Compound 17 Drugs 0.000 description 1
229940126639 Compound 33 Drugs 0.000 description 1
229940127007 Compound 39 Drugs 0.000 description 1
HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
239000004375 Dextrin Substances 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
208000032131 Diabetic Neuropathies Diseases 0.000 description 1
108060006698 EGF receptor Proteins 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
206010017533 Fungal infection Diseases 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
206010018364 Glomerulonephritis Diseases 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
206010073069 Hepatic cancer Diseases 0.000 description 1
208000017604 Hodgkin disease Diseases 0.000 description 1
101000846416 Homo sapiens Fibroblast growth factor 1 Proteins 0.000 description 1
101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
208000022559 Inflammatory bowel disease Diseases 0.000 description 1
206010023347 Keratoacanthoma Diseases 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 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
GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
208000031888 Mycoses Diseases 0.000 description 1
LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 1
POFVJRKJJBFPII-UHFFFAOYSA-N N-cyclopentyl-5-[2-[[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]amino]-5-fluoropyrimidin-4-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound C1(CCCC1)NC=1SC(=C(N=1)C)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1CCN(CC1)CC POFVJRKJJBFPII-UHFFFAOYSA-N 0.000 description 1
XTUVJUMINZSXGF-UHFFFAOYSA-N N-methylcyclohexylamine Chemical group CNC1CCCCC1 XTUVJUMINZSXGF-UHFFFAOYSA-N 0.000 description 1
125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
NHJSWORVNIOXIT-UHFFFAOYSA-N PD-166866 Chemical compound COC1=CC(OC)=CC(C=2C(=NC3=NC(N)=NC=C3C=2)NC(=O)NC(C)(C)C)=C1 NHJSWORVNIOXIT-UHFFFAOYSA-N 0.000 description 1
108091008606 PDGF receptors Proteins 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
241001494479 Pecora Species 0.000 description 1
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
108010076669 Proline-Directed Protein Kinases Proteins 0.000 description 1
102000011732 Proline-Directed Protein Kinases Human genes 0.000 description 1
108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
206010038389 Renal cancer Diseases 0.000 description 1
201000000582 Retinoblastoma Diseases 0.000 description 1
206010039491 Sarcoma Diseases 0.000 description 1
201000010208 Seminoma Diseases 0.000 description 1
102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
240000006474 Theobroma bicolor Species 0.000 description 1
240000006909 Tilia x europaea Species 0.000 description 1
235000011941 Tilia x europaea Nutrition 0.000 description 1
208000031737 Tissue Adhesions Diseases 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
206010052779 Transplant rejections Diseases 0.000 description 1
229920004890 Triton X-100 Polymers 0.000 description 1
239000013504 Triton X-100 Substances 0.000 description 1
LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 1
SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 1
LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 1
JFBZPFYRPYOZCQ-UHFFFAOYSA-N [Li].[Al] Chemical compound [Li].[Al] JFBZPFYRPYOZCQ-UHFFFAOYSA-N 0.000 description 1
SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
208000009956 adenocarcinoma Diseases 0.000 description 1
QBYJBZPUGVGKQQ-SJJAEHHWSA-N aldrin Chemical compound C1[C@H]2C=C[C@@H]1[C@H]1[C@@](C3(Cl)Cl)(Cl)C(Cl)=C(Cl)[C@@]3(Cl)[C@H]12 QBYJBZPUGVGKQQ-SJJAEHHWSA-N 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
125000003282 alkyl amino group Chemical group 0.000 description 1
230000007815 allergy Effects 0.000 description 1
BIIVYFLTOXDAOV-YVEFUNNKSA-N alvocidib Chemical compound O[C@@H]1CN(C)CC[C@@H]1C1=C(O)C=C(O)C2=C1OC(C=1C(=CC=CC=1)Cl)=CC2=O BIIVYFLTOXDAOV-YVEFUNNKSA-N 0.000 description 1
229950010817 alvocidib Drugs 0.000 description 1
230000006229 amino acid addition Effects 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
239000003708 ampul Substances 0.000 description 1
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
230000003527 anti-angiogenesis Effects 0.000 description 1
230000002788 anti-peptide Effects 0.000 description 1
230000001028 anti-proliverative effect Effects 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
229960004405 aprotinin Drugs 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
235000021311 artificial sweeteners Nutrition 0.000 description 1
239000012131 assay buffer Substances 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
201000001531 bladder carcinoma Diseases 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
230000037396 body weight Effects 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
210000000133 brain stem Anatomy 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
125000001589 carboacyl group Chemical group 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
230000006369 cell cycle progression Effects 0.000 description 1
239000013592 cell lysate Substances 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
235000010980 cellulose Nutrition 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
229940116592 central nervous system diagnostic radiopharmaceuticals Drugs 0.000 description 1
210000003679 cervix uteri Anatomy 0.000 description 1
229940081733 cetearyl alcohol Drugs 0.000 description 1
229940056318 ceteth-20 Drugs 0.000 description 1
239000013000 chemical inhibitor Substances 0.000 description 1
235000019693 cherries Nutrition 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
229940125773 compound 10 Drugs 0.000 description 1
229940126543 compound 14 Drugs 0.000 description 1
229940125758 compound 15 Drugs 0.000 description 1
229940126142 compound 16 Drugs 0.000 description 1
229940125782 compound 2 Drugs 0.000 description 1
229940125810 compound 20 Drugs 0.000 description 1
229940126086 compound 21 Drugs 0.000 description 1
229940126208 compound 22 Drugs 0.000 description 1
229940125833 compound 23 Drugs 0.000 description 1
229940125961 compound 24 Drugs 0.000 description 1
229940125846 compound 25 Drugs 0.000 description 1
229940125851 compound 27 Drugs 0.000 description 1
229940127204 compound 29 Drugs 0.000 description 1
229940126214 compound 3 Drugs 0.000 description 1
229940125877 compound 31 Drugs 0.000 description 1
229940125878 compound 36 Drugs 0.000 description 1
229940125807 compound 37 Drugs 0.000 description 1
229940127573 compound 38 Drugs 0.000 description 1
229940126540 compound 41 Drugs 0.000 description 1
229940125936 compound 42 Drugs 0.000 description 1
229940125844 compound 46 Drugs 0.000 description 1
229940127271 compound 49 Drugs 0.000 description 1
229940125898 compound 5 Drugs 0.000 description 1
229940126545 compound 53 Drugs 0.000 description 1
229940127113 compound 57 Drugs 0.000 description 1
229940125900 compound 59 Drugs 0.000 description 1
229940126179 compound 72 Drugs 0.000 description 1
UUYYJWFAHPQMJY-UHFFFAOYSA-N cyanomethoxy-oxido-oxophosphanium Chemical compound [O-][P+](=O)OCC#N UUYYJWFAHPQMJY-UHFFFAOYSA-N 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
229940043378 cyclin-dependent kinase inhibitor Drugs 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
230000001419 dependent effect Effects 0.000 description 1
238000013461 design Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
125000005265 dialkylamine group Chemical group 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000013024 dilution buffer Substances 0.000 description 1
125000000532 dioxanyl group Chemical group 0.000 description 1
XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
235000011180 diphosphates Nutrition 0.000 description 1
WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical group CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
208000037765 diseases and disorders Diseases 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
229940079593 drug Drugs 0.000 description 1
241001493065 dsRNA viruses Species 0.000 description 1
BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 0.000 description 1
238000001952 enzyme assay Methods 0.000 description 1
SIHZWGODIRRSRA-ONEGZZNKSA-N erbstatin Chemical compound OC1=CC=C(O)C(\C=C\NC=O)=C1 SIHZWGODIRRSRA-ONEGZZNKSA-N 0.000 description 1
210000003238 esophagus Anatomy 0.000 description 1
FVPISMANESAJQZ-UHFFFAOYSA-N ethyl 2-diethoxyphosphoryl-2-fluoroacetate Chemical compound CCOC(=O)C(F)P(=O)(OCC)OCC FVPISMANESAJQZ-UHFFFAOYSA-N 0.000 description 1
GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 description 1
ISFANEDJKPPHBJ-UHFFFAOYSA-N ethyl 7-amino-2-chloropyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N1=C(Cl)N=C2N=C(N)C(C(=O)OCC)=CC2=C1 ISFANEDJKPPHBJ-UHFFFAOYSA-N 0.000 description 1
YCWDQAKDVQNVAR-UHFFFAOYSA-N ethyl pyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=CN=C1 YCWDQAKDVQNVAR-UHFFFAOYSA-N 0.000 description 1
DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
229930003935 flavonoid Natural products 0.000 description 1
150000002215 flavonoids Chemical class 0.000 description 1
235000017173 flavonoids Nutrition 0.000 description 1
239000012530 fluid Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000012458 free base Substances 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000011521 glass Substances 0.000 description 1
239000008103 glucose Substances 0.000 description 1
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
206010073071 hepatocellular carcinoma Diseases 0.000 description 1
125000004415 heterocyclylalkyl group Chemical group 0.000 description 1
IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
239000005457 ice water Substances 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
230000000415 inactivating effect Effects 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
230000003993 interaction Effects 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
230000007794 irritation Effects 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000005921 isopentoxy group Chemical group 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
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 1
229940099584 lactobionate Drugs 0.000 description 1
JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
239000008101 lactose Substances 0.000 description 1
210000002429 large intestine Anatomy 0.000 description 1
239000004816 latex Substances 0.000 description 1
229920000126 latex Polymers 0.000 description 1
229940070765 laurate Drugs 0.000 description 1
GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
108010052968 leupeptin Proteins 0.000 description 1
239000004571 lime Substances 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
201000002250 liver carcinoma Diseases 0.000 description 1
RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 1
201000005202 lung cancer Diseases 0.000 description 1
206010025135 lupus erythematosus Diseases 0.000 description 1
239000012139 lysis buffer Substances 0.000 description 1
208000002780 macular degeneration Diseases 0.000 description 1
NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 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
239000012528 membrane Substances 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
239000011859 microparticle Substances 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
229940045641 monobasic sodium phosphate Drugs 0.000 description 1
229910000403 monosodium phosphate Inorganic materials 0.000 description 1
235000019799 monosodium phosphate Nutrition 0.000 description 1
201000006417 multiple sclerosis Diseases 0.000 description 1
210000000663 muscle cell Anatomy 0.000 description 1
DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
YCJZWBZJSYLMPB-UHFFFAOYSA-N n-(2-chloropyrimidin-4-yl)-2,5-dimethyl-1-phenylimidazole-4-carboxamide Chemical compound CC=1N(C=2C=CC=CC=2)C(C)=NC=1C(=O)NC1=CC=NC(Cl)=N1 YCJZWBZJSYLMPB-UHFFFAOYSA-N 0.000 description 1
FRTLPVFIQJYINI-UHFFFAOYSA-N n-[2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]acetamide Chemical compound N=1C2=NC(NC(=O)C)=CC=C2C=NC=1NC(C=C1)=CC=C1N1CCNCC1 FRTLPVFIQJYINI-UHFFFAOYSA-N 0.000 description 1
CYSOBNVWOAGUIR-UHFFFAOYSA-N n-[6-bromo-2-[4-[2-(diethylamino)ethoxy]anilino]pyrido[2,3-d]pyrimidin-7-yl]acetamide;hydrochloride Chemical compound Cl.C1=CC(OCCN(CC)CC)=CC=C1NC1=NC=C(C=C(Br)C(NC(C)=O)=N2)C2=N1 CYSOBNVWOAGUIR-UHFFFAOYSA-N 0.000 description 1
125000006606 n-butoxy group Chemical group 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000005487 naphthalate group Chemical group 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
235000021096 natural sweeteners Nutrition 0.000 description 1
IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 1
230000004770 neurodegeneration Effects 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
125000006574 non-aromatic ring group Chemical group 0.000 description 1
GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
229940049964 oleate Drugs 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
GTVPOLSIJWJJNY-UHFFFAOYSA-N olomoucine Chemical compound N1=C(NCCO)N=C2N(C)C=NC2=C1NCC1=CC=CC=C1 GTVPOLSIJWJJNY-UHFFFAOYSA-N 0.000 description 1
PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
229940100692 oral suspension Drugs 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
201000010198 papillary carcinoma Diseases 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
229950000964 pepstatin Drugs 0.000 description 1
108010091212 pepstatin Proteins 0.000 description 1
FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
235000019271 petrolatum Nutrition 0.000 description 1
125000005561 phenanthryl group Chemical group 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
125000005545 phthalimidyl group Chemical group 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000005936 piperidyl group Chemical group 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
238000000746 purification Methods 0.000 description 1
QRRCMVPZJCHBLQ-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine-2,7-diamine Chemical class C1=NC(N)=NC2=NC(N)=CC=C21 QRRCMVPZJCHBLQ-UHFFFAOYSA-N 0.000 description 1
159000000018 pyrido[2,3-d]pyrimidines Chemical class 0.000 description 1
UVBZDRKTCAJYLN-UHFFFAOYSA-N pyrido[3,2-d]pyrimidin-7-amine Chemical compound C1=NC=NC2=CC(N)=CN=C21 UVBZDRKTCAJYLN-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
150000003230 pyrimidines Chemical class 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
229940048084 pyrophosphate Drugs 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
239000000376 reactant Substances 0.000 description 1
108091008598 receptor tyrosine kinases Proteins 0.000 description 1
102000027426 receptor tyrosine kinases Human genes 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
201000010174 renal carcinoma Diseases 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
230000004044 response Effects 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
230000019491 signal transduction Effects 0.000 description 1
XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
210000000813 small intestine Anatomy 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229940083608 sodium hydroxide Drugs 0.000 description 1
CMZUMMUJMWNLFH-UHFFFAOYSA-N sodium metavanadate Chemical compound [Na+].[O-][V](=O)=O CMZUMMUJMWNLFH-UHFFFAOYSA-N 0.000 description 1
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
206010041823 squamous cell carcinoma Diseases 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000005017 substituted alkenyl group Chemical group 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
QAHVHSLSRLSVGS-UHFFFAOYSA-N sulfamoyl chloride Chemical compound NS(Cl)(=O)=O QAHVHSLSRLSVGS-UHFFFAOYSA-N 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
GSALRQQUCCLTEJ-BETUJISGSA-N tert-butyl (2s,6r)-4-(4-aminophenyl)-2,6-dimethylpiperazine-1-carboxylate Chemical compound C1[C@@H](C)N(C(=O)OC(C)(C)C)[C@@H](C)CN1C1=CC=C(N)C=C1 GSALRQQUCCLTEJ-BETUJISGSA-N 0.000 description 1
MGYCIJUTYLUYJM-UHFFFAOYSA-N tert-butyl 4-(4-nitrophenyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C([N+]([O-])=O)C=C1 MGYCIJUTYLUYJM-UHFFFAOYSA-N 0.000 description 1
OSBIEGRZGZRSBF-UHFFFAOYSA-N tert-butyl 4-[4-[(5-acetyl-4-aminopyrimidin-2-yl)amino]phenyl]piperazine-1-carboxylate Chemical compound N1=C(N)C(C(=O)C)=CN=C1NC1=CC=C(N2CCN(CC2)C(=O)OC(C)(C)C)C=C1 OSBIEGRZGZRSBF-UHFFFAOYSA-N 0.000 description 1
PWUUIKXPHXIFIT-UHFFFAOYSA-N tert-butyl 4-[4-[(7-amino-5-methylpyrido[2,3-d]pyrimidin-2-yl)amino]phenyl]piperazine-1-carboxylate Chemical group N=1C=C2C(C)=CC(N)=NC2=NC=1NC(C=C1)=CC=C1N1CCN(C(=O)OC(C)(C)C)CC1 PWUUIKXPHXIFIT-UHFFFAOYSA-N 0.000 description 1
FSVJKTYULHABKQ-UHFFFAOYSA-N tert-butyl 4-[4-[(7-amino-6-fluoropyrido[2,3-d]pyrimidin-2-yl)amino]phenyl]-2,2-dimethylpiperazine-1-carboxylate Chemical compound C1C(C)(C)N(C(=O)OC(C)(C)C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=C(F)C(N)=N2)C2=N1 FSVJKTYULHABKQ-UHFFFAOYSA-N 0.000 description 1
UBSVDMOMDQNVDD-QFIPXVFZSA-N tert-butyl 4-[4-[[7-[[(2r)-1-hydroxy-3-methylbutan-2-yl]carbamoylamino]pyrido[2,3-d]pyrimidin-2-yl]amino]phenyl]piperazine-1-carboxylate Chemical compound N=1C2=NC(NC(=O)N[C@@H](CO)C(C)C)=CC=C2C=NC=1NC(C=C1)=CC=C1N1CCN(C(=O)OC(C)(C)C)CC1 UBSVDMOMDQNVDD-QFIPXVFZSA-N 0.000 description 1
210000001550 testis Anatomy 0.000 description 1
CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
125000006000 trichloroethyl group Chemical group 0.000 description 1
IIHPVYJPDKJYOU-UHFFFAOYSA-N triphenylcarbethoxymethylenephosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OCC)C1=CC=CC=C1 IIHPVYJPDKJYOU-UHFFFAOYSA-N 0.000 description 1
231100000588 tumorigenic Toxicity 0.000 description 1
230000000381 tumorigenic effect Effects 0.000 description 1
208000010576 undifferentiated carcinoma Diseases 0.000 description 1
150000003672 ureas Chemical class 0.000 description 1
208000010570 urinary bladder carcinoma Diseases 0.000 description 1
229940070710 valerate Drugs 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000002792 vascular Effects 0.000 description 1
239000011345 viscous material Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000003871 white petrolatum Substances 0.000 description 1
229910000166 zirconium phosphate Inorganic materials 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Neurology (AREA)
Molecular Biology (AREA)
Biochemistry (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Vascular Medicine (AREA)
Hospice & Palliative Care (AREA)
Heart & Thoracic Surgery (AREA)
Psychiatry (AREA)
Dermatology (AREA)
Urology & Nephrology (AREA)
Cardiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Enzymes And Modification Thereof (AREA)

OA1200200213A 2000-01-25 2001-01-23 PyridoÄ2,3-dÜpyrimidine-2,7-diamine kinase inhibitors. OA12161A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US17826100P	2000-01-25	2000-01-25

Publications (1)

Publication Number	Publication Date
OA12161A true OA12161A (en)	2006-05-08

Family

ID=22651853

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA1200200213A OA12161A (en)	2000-01-25	2001-01-23	PyridoÄ2,3-dÜpyrimidine-2,7-diamine kinase inhibitors.

Country Status (34)

Country	Link
EP (1)	EP1254137A1 (fr)
JP (1)	JP4047010B2 (fr)
KR (1)	KR20020065939A (fr)
CN (1)	CN1395578A (fr)
AP (1)	AP2002002586A0 (fr)
AR (1)	AR030044A1 (fr)
AU (1)	AU2542501A (fr)
BG (1)	BG106850A (fr)
BR (1)	BR0107751A (fr)
CA (1)	CA2397961C (fr)
CO (1)	CO5261549A1 (fr)
CR (1)	CR6706A (fr)
CZ (1)	CZ20022475A3 (fr)
DZ (1)	DZ3266A1 (fr)
EA (1)	EA200200643A1 (fr)
EE (1)	EE200200405A (fr)
GT (1)	GT200100016A (fr)
HN (1)	HN2001000013A (fr)
HU (1)	HUP0204141A3 (fr)
IL (1)	IL150545A0 (fr)
IS (1)	IS6443A (fr)
MA (1)	MA26868A1 (fr)
MX (1)	MXPA02007221A (fr)
NO (1)	NO20023527L (fr)
OA (1)	OA12161A (fr)
PA (1)	PA8510701A1 (fr)
PE (1)	PE20011066A1 (fr)
PL (1)	PL356802A1 (fr)
SK (1)	SK10632002A3 (fr)
SV (1)	SV2002000294A (fr)
TN (1)	TNSN01014A1 (fr)
WO (1)	WO2001055147A1 (fr)
YU (1)	YU50402A (fr)
ZA (1)	ZA200205879B (fr)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7235551B2 (en)	2000-03-02	2007-06-26	Smithkline Beecham Corporation	1,5-disubstituted-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one compounds and their use in treating csbp/p38 kinase mediated diseases
EP2404603A1 (fr)	2000-10-23	2012-01-11	Glaxosmithkline LLC	Nouveaux composés 8H-pyrido[2,3-d]pyrimidin-7-one trisubstituté pour le traitement des maladies faisant intervenir les kinases CSBP/p38.
PE20030008A1 (es) *	2001-06-19	2003-01-22	Bristol Myers Squibb Co	Inhibidores duales de pde 7 y pde 4
MXPA04010267A (es)	2002-04-19	2005-02-03	Smithkline Beecham Corp	Compuestos novedosos.
KR20050084027A (ko) *	2002-11-28	2005-08-26	쉐링 악티엔게젤샤프트	Ｃｈｋ-, ｐｄｋ- 및 ａｋｔ-억제성 피리미딘, 그의제조방법 및 약제로서의 그의 용도
US7157455B2 (en) *	2003-02-10	2007-01-02	Hoffmann-La Roche Inc.	4-Aminopyrimidine-5-one derivatives
TW200502236A (en) *	2003-03-28	2005-01-16	Hoffmann La Roche	Novel pyrido[2,3-d]pyrimidin-7-carboxylic acid derivatives, their manufacture and use as pharmaceutical agents
FR2873118B1 (fr)	2004-07-15	2007-11-23	Sanofi Synthelabo	Derives de pyrido-pyrimidine, leur application en therapeutique
US7550589B2 (en) *	2004-09-21	2009-06-23	Hoffman-La Roche Inc.	6-(2-alkyl-phenyl)-pyrido[2,3-D]pyrimidines useful as protein kinase inhibitors
PE20061351A1 (es)	2005-03-25	2007-01-14	Glaxo Group Ltd	COMPUESTOS 8H-PIRIDO[2,3-d]PIRIMIDIN-7-ONA 2,4,8-TRISUSTITUIDOS COMO INHIBIDORES DE LA QUINASA CSBP/RK/p38
US20090137550A1 (en)	2005-03-25	2009-05-28	Glaxo Group Limited	Novel Compounds
TW200724142A (en)	2005-03-25	2007-07-01	Glaxo Group Ltd	Novel compounds
EP1865959A2 (fr)	2005-03-25	2007-12-19	Glaxo Group Limited	Procede de preparation de derives pyridoý2,3-d¨pyrimidin-7-one et 3,4-dihydropyrimidoý4,5-d¨pyrimidin-2(1h)-one
FR2887882B1 (fr) *	2005-07-01	2007-09-07	Sanofi Aventis Sa	Derives de pyrido[2,3-d] pyrimidine, leur preparation, leur application en therapeutique
WO2007009911A1 (fr) *	2005-07-21	2007-01-25	F. Hoffmann-La Roche Ag	Composes pyrido [2, 3-d] pyrimidine-2, 4-diamine utilises comme inhibiteurs de ptp1b
AU2006279992A1 (en)	2005-08-09	2007-02-22	Irm Llc	Compounds and compositions as protein kinase inhibitors
FR2896246B1 (fr)	2006-01-13	2008-08-15	Sanofi Aventis Sa	Derives de pyrido-pyrimidone, leur preparation, leur application en therapeutique.
EP1914234A1 (fr)	2006-10-16	2008-04-23	GPC Biotech Inc.	Pyrido[2,3-d]pyrimidines et leur utilisation comme inhibiteurs de kinases
JO2985B1 (ar)	2006-12-20	2016-09-05	Takeda Pharmaceuticals Co	مثبطات كينازmapk/erk
FR2910813B1 (fr) *	2006-12-28	2009-02-06	Sanofi Aventis Sa	Nouvelle utilisation therapeutique pour le traitement des leucemies
EP2112150B1 (fr)	2008-04-22	2013-10-16	Forma Therapeutics, Inc.	Inhibiteurs Raf améliorés
EA201100879A1 (ru) *	2008-12-01	2012-01-30	Мерк Патент Гмбх	Производные пиридопиримидина в качестве ингибиторов аутотаксина
GB201104267D0 (en)	2011-03-14	2011-04-27	Cancer Rec Tech Ltd	Pyrrolopyridineamino derivatives
GB201216017D0 (en)	2012-09-07	2012-10-24	Cancer Rec Tech Ltd	Inhibitor compounds
GB201216018D0 (en)	2012-09-07	2012-10-24	Cancer Rec Tech Ltd	Pharmacologically active compounds
EP3733184B1 (fr) *	2013-03-14	2023-08-30	Icahn School of Medicine at Mount Sinai	Composés de pyrimidine pour l'utililisation dans la traitment de cancer
GB201403536D0 (en)	2014-02-28	2014-04-16	Cancer Rec Tech Ltd	Inhibitor compounds
KR101671404B1 (ko) *	2014-09-02	2016-11-02	한국원자력의학원	항암 효과, 방사선 병용치료 효과 및 당뇨병 치료 효과를 갖는 피리미딘 유도체 및 이의 의학적 용도
CN107286180B (zh) *	2016-04-11	2019-07-02	上海勋和医药科技有限公司	杂代吡啶并嘧啶酮衍生物作为cdk抑制剂及其应用
GB201709840D0 (en)	2017-06-20	2017-08-02	Inst Of Cancer Research: Royal Cancer Hospital	Methods and medical uses

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL115256A0 (en) *	1994-11-14	1995-12-31	Warner Lambert Co	6-Aryl pyrido (2,3-d) pyrimidines and naphthyridines and their use
MX9702245A (es) *	1994-11-14	1997-06-28	Warner Lambert Co	Seis-aril-pirido(2,3-d)pirimidinas y naftiridinas para inhibir la proliferacion celular mediada por la proteina cinasa tirosina.
US5620981A (en) *	1995-05-03	1997-04-15	Warner-Lambert Company	Pyrido [2,3-D]pyrimidines for inhibiting protein tyrosine kinase mediated cellular proliferation
EE200000706A (et) *	1998-05-26	2002-06-17	Warner-Lambert Company	Bitsüklilised pürimidiinid ja bitsüklilised 3,4-dihüdropürimidiinid kui rakkude proliferatsiooni inhibiitorid

2001
- 2001-01-23 WO PCT/IB2001/000069 patent/WO2001055147A1/fr not_active Ceased
- 2001-01-23 EE EEP200200405A patent/EE200200405A/xx unknown
- 2001-01-23 YU YU50402A patent/YU50402A/sh unknown
- 2001-01-23 PA PA20018510701A patent/PA8510701A1/es unknown
- 2001-01-23 HU HU0204141A patent/HUP0204141A3/hu unknown
- 2001-01-23 DZ DZ013266A patent/DZ3266A1/fr active
- 2001-01-23 EA EA200200643A patent/EA200200643A1/ru unknown
- 2001-01-23 EP EP01900591A patent/EP1254137A1/fr not_active Withdrawn
- 2001-01-23 AR ARP010100285A patent/AR030044A1/es not_active Application Discontinuation
- 2001-01-23 CZ CZ20022475A patent/CZ20022475A3/cs unknown
- 2001-01-23 SK SK1063-2002A patent/SK10632002A3/sk not_active Application Discontinuation
- 2001-01-23 CA CA002397961A patent/CA2397961C/fr not_active Expired - Fee Related
- 2001-01-23 PE PE2001000072A patent/PE20011066A1/es not_active Application Discontinuation
- 2001-01-23 OA OA1200200213A patent/OA12161A/en unknown
- 2001-01-23 BR BR0107751-1A patent/BR0107751A/pt not_active IP Right Cessation
- 2001-01-23 JP JP2001561006A patent/JP4047010B2/ja not_active Expired - Fee Related
- 2001-01-23 GT GT200100016A patent/GT200100016A/es unknown
- 2001-01-23 MX MXPA02007221A patent/MXPA02007221A/es not_active Application Discontinuation
- 2001-01-23 AU AU25425/01A patent/AU2542501A/en not_active Abandoned
- 2001-01-23 PL PL01356802A patent/PL356802A1/xx not_active Application Discontinuation
- 2001-01-23 KR KR1020027009516A patent/KR20020065939A/ko not_active Ceased
- 2001-01-23 CN CN01804048A patent/CN1395578A/zh active Pending
- 2001-01-23 AP APAP/P/2002/002586A patent/AP2002002586A0/en unknown
- 2001-01-23 IL IL15054501A patent/IL150545A0/xx unknown
- 2001-01-24 CO CO01005268A patent/CO5261549A1/es not_active Application Discontinuation
- 2001-01-24 SV SV2001000294A patent/SV2002000294A/es not_active Application Discontinuation
- 2001-01-24 TN TNTNSN01014A patent/TNSN01014A1/fr unknown
- 2001-01-24 HN HN2001000013A patent/HN2001000013A/es unknown
2002
- 2002-06-20 BG BG106850A patent/BG106850A/bg unknown
- 2002-06-25 IS IS6443A patent/IS6443A/is unknown
- 2002-07-17 CR CR6706A patent/CR6706A/es not_active Application Discontinuation
- 2002-07-22 MA MA26736A patent/MA26868A1/fr unknown
- 2002-07-23 ZA ZA200205879A patent/ZA200205879B/en unknown
- 2002-07-24 NO NO20023527A patent/NO20023527L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
TNSN01014A1 (fr)	2005-11-10
NO20023527L (no)	2002-09-10
PL356802A1 (en)	2004-07-12
CZ20022475A3 (cs)	2003-03-12
AP2002002586A0 (en)	2002-09-30
JP2003523357A (ja)	2003-08-05
WO2001055147A1 (fr)	2001-08-02
EA200200643A1 (ru)	2002-12-26
CN1395578A (zh)	2003-02-05
EP1254137A1 (fr)	2002-11-06
CA2397961C (fr)	2008-08-26
YU50402A (sh)	2005-11-28
MA26868A1 (fr)	2004-12-20
CA2397961A1 (fr)	2001-08-02
NO20023527D0 (no)	2002-07-24
KR20020065939A (ko)	2002-08-14
BG106850A (bg)	2003-02-28
CO5261549A1 (es)	2003-03-31
DZ3266A1 (fr)	2001-08-02
HUP0204141A2 (hu)	2003-04-28
GT200100016A (es)	2001-10-19
AU2542501A (en)	2001-08-07
IL150545A0 (en)	2003-02-12
BR0107751A (pt)	2002-11-12
IS6443A (is)	2002-06-25
HUP0204141A3 (en)	2005-03-29
SV2002000294A (es)	2002-07-16
SK10632002A3 (sk)	2003-06-03
HN2001000013A (es)	2001-06-18
AR030044A1 (es)	2003-08-13
ZA200205879B (en)	2003-09-29
PA8510701A1 (es)	2002-12-11
CR6706A (es)	2005-04-04
MXPA02007221A (es)	2002-11-29
EE200200405A (et)	2003-12-15
PE20011066A1 (es)	2001-10-22
JP4047010B2 (ja)	2008-02-13

Publication	Publication Date	Title
CA2397961C (fr)	2008-08-26	Inhibiteurs de pyrido[2,3-d]pyrimidine-2,7-diamine kinase
US7053070B2 (en)	2006-05-30	Pyrido[2,3-d]pyrimidine-2,7-diamine kinase inhibitors
US7244729B2 (en)	2007-07-17	4-amino-6-phenyl-pyrrolo[2,3-d]pyrimidine derivatives
AU777468B2 (en)	2004-10-21	Pteridinones as kinase inhibitors
ES2274526T3 (es)	2007-05-16	Pirido(2,3-d)pirimidinas para inhibir la proliferacion celular mediada por tirosinaquinasa.
US20090312321A1 (en)	2009-12-17	Compositions and methods for fgf receptor kinases inhibitors
OA12227A (en)	2004-03-18	5-AlkylpyridoÄ2,3-DÜpyrimidines tyrosine kinase inhibitors.
EP1080092A2 (fr)	2001-03-07	Pyrimidines bicycliques et 3,4-dihydropyrimidines bicycliques, inhibiteurs de proliferation cellulaire
KR19990008252A (ko)	1999-01-25	단백질 티로신 키나제 매개된 세포 증식을 억제하기 위한 피리도[2,3-ｄ]피리미딘
JP2015519396A (ja)	2015-07-09	Ｊａｋ１およびｊａｋ２の阻害剤
US7323469B2 (en)	2008-01-29	7H-pyrrolo[2,3-d]pyrimidine derivatives
HK1065483B (en)	2008-08-22	4-amino-6-phenyl-pyrrolo[2,3-d]pyrimidine derivatives