NO325987B1 - Pyrimidinaminer, anvendelse derav samt farmasoytisk preparat. - Google Patents

Pyrimidinaminer, anvendelse derav samt farmasoytisk preparat. Download PDF

Info

Publication number: NO325987B1
Authority: NO; Norway
Prior art keywords: methyl; amino; indazol; alkyl; pyrimidinyl
Prior art date: 2000-12-21

Application number

NO20032831A

Other languages

English (en)

Norwegian (no)

Other versions

NO20032831L (no

NO20032831D0 (no

Inventor

Robert Anthony Mook

James Martin Veal

Amogh Boloor

Mui Cheng

Ronda Davis

Phillip Anthony Harris

Kevin Hinkle

Jeffrey Alan Stafford

Original Assignee

Glaxo Group Ltd

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.)

2000-12-21

Filing date

2003-06-20

Publication date

2008-08-25

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26946028&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=NO325987(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2003-06-20 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

2003-06-20 Publication of NO20032831D0 publication Critical patent/NO20032831D0/no

2003-08-15 Publication of NO20032831L publication Critical patent/NO20032831L/no

2008-08-25 Publication of NO325987B1 publication Critical patent/NO325987B1/no

Links

239000000825 pharmaceutical preparation Substances 0.000 title claims description 21
LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical class NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 title 1
238000011282 treatment Methods 0.000 claims abstract description 20
150000001875 compounds Chemical class 0.000 claims description 127
-1 cyanomethylene Chemical group 0.000 claims description 96
239000001257 hydrogen Substances 0.000 claims description 81
229910052739 hydrogen Inorganic materials 0.000 claims description 81
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 72
150000002431 hydrogen Chemical class 0.000 claims description 62
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 49
238000002360 preparation method Methods 0.000 claims description 44
150000003839 salts Chemical class 0.000 claims description 42
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 39
125000000217 alkyl group Chemical group 0.000 claims description 39
229910052736 halogen Inorganic materials 0.000 claims description 39
150000002367 halogens Chemical group 0.000 claims description 39
WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 34
125000001188 haloalkyl group Chemical group 0.000 claims description 29
239000012453 solvate Substances 0.000 claims description 29
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 25
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
125000000753 cycloalkyl group Chemical group 0.000 claims description 23
239000000460 chlorine Chemical group 0.000 claims description 20
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
206010028980 Neoplasm Diseases 0.000 claims description 18
229910052757 nitrogen Inorganic materials 0.000 claims description 15
201000011510 cancer Diseases 0.000 claims description 14
125000003545 alkoxy group Chemical group 0.000 claims description 13
125000004093 cyano group Chemical group *C#N 0.000 claims description 12
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 12
239000003814 drug Substances 0.000 claims description 11
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 9
229940079593 drug Drugs 0.000 claims description 9
GMMWNTHAIOJBSD-UHFFFAOYSA-N 6-chloro-4-n-(2,3-dimethylphenyl)-2-n,2-n-dimethylpyrimidine-2,4-diamine Chemical compound CN(C)C1=NC(Cl)=CC(NC=2C(=C(C)C=CC=2)C)=N1 GMMWNTHAIOJBSD-UHFFFAOYSA-N 0.000 claims description 8
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
229910052801 chlorine Inorganic materials 0.000 claims description 8
238000002560 therapeutic procedure Methods 0.000 claims description 8
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 7
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 6
239000003085 diluting agent Substances 0.000 claims description 5
HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 5
YTTBOOLPGZCTSF-UHFFFAOYSA-N 3-[[4-[[2-[(3-chlorophenyl)methyl]-3-methylindazol-6-yl]-methylamino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound C=1C=NC(NC=2C=C(C=CC=2)S(N)(=O)=O)=NC=1N(C)C(=CC1=N2)C=CC1=C(C)N2CC1=CC=CC(Cl)=C1 YTTBOOLPGZCTSF-UHFFFAOYSA-N 0.000 claims description 4
239000000654 additive Substances 0.000 claims description 4
CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 claims description 4
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 4
OVTQMMYLOJBKOP-UHFFFAOYSA-N 1-[4-[[5-fluoro-4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]phenyl]-n-methylmethanesulfonamide Chemical compound C1=CC(CS(=O)(=O)NC)=CC=C1NC1=NC=C(F)C(N(C)C=2C=C3NN=C(C)C3=CC=2)=N1 OVTQMMYLOJBKOP-UHFFFAOYSA-N 0.000 claims description 3
BPGZHRULBGZUFP-UHFFFAOYSA-N 1-[4-methoxy-3-[[4-[(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]phenyl]propan-1-one Chemical compound CCC(=O)C1=CC=C(OC)C(NC=2N=C(NC=3C=C4NN=C(C)C4=CC=3)C=CN=2)=C1 BPGZHRULBGZUFP-UHFFFAOYSA-N 0.000 claims description 3
MQYXDHFLBFNMAM-UHFFFAOYSA-N 2-[(3-methyl-2h-indazol-6-yl)-[2-[4-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]acetonitrile Chemical compound C=1C=C2C(C)=NNC2=CC=1N(CC#N)C(N=1)=CC=NC=1NC1=CC=C(CS(C)(=O)=O)C=C1 MQYXDHFLBFNMAM-UHFFFAOYSA-N 0.000 claims description 3
RLIRKBLVQDRMIA-UHFFFAOYSA-N 3-[[4-[(2,3-dimethylindazol-6-yl)-methylamino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=CC(S(N)(=O)=O)=C1 RLIRKBLVQDRMIA-UHFFFAOYSA-N 0.000 claims description 3
HQBJXXBUOZHSGV-UHFFFAOYSA-N 3-[[4-[(3-methyl-2h-indazol-6-yl)-prop-2-ynylamino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(CC#C)C(N=1)=CC=NC=1NC1=CC=CC(S(N)(=O)=O)=C1 HQBJXXBUOZHSGV-UHFFFAOYSA-N 0.000 claims description 3
HSCPAFQDYZFJML-UHFFFAOYSA-N 3-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=CC=NC=1NC1=CC=CC(S(N)(=O)=O)=C1 HSCPAFQDYZFJML-UHFFFAOYSA-N 0.000 claims description 3
CBNFOUWNKLWLNA-UHFFFAOYSA-N 3-[[5-fluoro-4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]-4-methoxybenzamide Chemical compound COC1=CC=C(C(N)=O)C=C1NC1=NC=C(F)C(N(C)C=2C=C3NN=C(C)C3=CC=2)=N1 CBNFOUWNKLWLNA-UHFFFAOYSA-N 0.000 claims description 3
KGLPIORBSZRHNX-UHFFFAOYSA-N 3-methyl-4-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=CC=NC=1NC1=CC=C(S(N)(=O)=O)C=C1C KGLPIORBSZRHNX-UHFFFAOYSA-N 0.000 claims description 3
XOJHOUVWPOFGRW-UHFFFAOYSA-N 4-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=CC=NC=1NC1=CC=C(S(N)(=O)=O)C=C1 XOJHOUVWPOFGRW-UHFFFAOYSA-N 0.000 claims description 3
ZUKWQTLSOWOKOR-UHFFFAOYSA-N 4-[[5-fluoro-4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]-3-methoxybenzenesulfonamide Chemical compound COC1=CC(S(N)(=O)=O)=CC=C1NC1=NC=C(F)C(N(C)C=2C=C3NN=C(C)C3=CC=2)=N1 ZUKWQTLSOWOKOR-UHFFFAOYSA-N 0.000 claims description 3
OTEXRPIJKRUVMS-UHFFFAOYSA-N 4-[[5-fluoro-4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C(C(=CN=1)F)=NC=1NC1=CC=C(S(N)(=O)=O)C=C1 OTEXRPIJKRUVMS-UHFFFAOYSA-N 0.000 claims description 3
GUWPQACNUZVRGI-UHFFFAOYSA-N 4-chloro-3-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=CC=NC=1NC1=CC(S(N)(=O)=O)=CC=C1Cl GUWPQACNUZVRGI-UHFFFAOYSA-N 0.000 claims description 3
LNURXKSLIOUNCJ-UHFFFAOYSA-N 4-methoxy-n-methyl-3-[[4-[(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC)C(NC=2N=C(NC=3C=C4NN=C(C)C4=CC=3)C=CN=2)=C1 LNURXKSLIOUNCJ-UHFFFAOYSA-N 0.000 claims description 3
DTVMIRCVMNZFLJ-UHFFFAOYSA-N 4-methoxy-n-methyl-3-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC)C(NC=2N=C(C=CN=2)N(C)C=2C=C3NN=C(C)C3=CC=2)=C1 DTVMIRCVMNZFLJ-UHFFFAOYSA-N 0.000 claims description 3
IDXNGTHGCYPLSM-UHFFFAOYSA-N 5-[[4-[(2,3-dimethylindazol-6-yl)-methylamino]-1,3,5-triazin-2-yl]amino]-2-methylbenzenesulfonamide Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=NC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 IDXNGTHGCYPLSM-UHFFFAOYSA-N 0.000 claims description 3
METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims description 3
125000004438 haloalkoxy group Chemical group 0.000 claims description 3
PUSFXFYZPRQPPI-UHFFFAOYSA-N n-cyclopropyl-3-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=CC=NC=1NC(C=1)=CC=CC=1S(=O)(=O)NC1CC1 PUSFXFYZPRQPPI-UHFFFAOYSA-N 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
JEPSYOCVHUMOMN-UHFFFAOYSA-N 2-chloro-4-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=CC=NC=1NC1=CC=C(S(N)(=O)=O)C(Cl)=C1 JEPSYOCVHUMOMN-UHFFFAOYSA-N 0.000 claims description 2
ATYSMJGLCLJPEP-UHFFFAOYSA-N 2-chloro-5-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=CC=NC=1NC1=CC=C(Cl)C(S(N)(=O)=O)=C1 ATYSMJGLCLJPEP-UHFFFAOYSA-N 0.000 claims description 2
BRBRXNGJZMGEHY-UHFFFAOYSA-N 2-methyl-5-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 BRBRXNGJZMGEHY-UHFFFAOYSA-N 0.000 claims description 2
YYEQVRSLWCBRFA-UHFFFAOYSA-N 3-[[4-[(2-benzyl-1-methylbenzimidazol-5-yl)-methylamino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound C=1C=NC(NC=2C=C(C=CC=2)S(N)(=O)=O)=NC=1N(C)C(C=C1N=2)=CC=C1N(C)C=2CC1=CC=CC=C1 YYEQVRSLWCBRFA-UHFFFAOYSA-N 0.000 claims description 2
RQLARVFITLQJPK-UHFFFAOYSA-N 3-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]-n-propan-2-ylbenzenesulfonamide Chemical compound CC(C)NS(=O)(=O)C1=CC=CC(NC=2N=C(C=CN=2)N(C)C=2C=C3NN=C(C)C3=CC=2)=C1 RQLARVFITLQJPK-UHFFFAOYSA-N 0.000 claims description 2
APOUZHQWQWVZSU-UHFFFAOYSA-N 3-methoxy-4-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound COC1=CC(S(N)(=O)=O)=CC=C1NC1=NC=CC(N(C)C=2C=C3NN=C(C)C3=CC=2)=N1 APOUZHQWQWVZSU-UHFFFAOYSA-N 0.000 claims description 2
VEPLCBIWJQEWSM-UHFFFAOYSA-N 4-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]benzamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=CC=NC=1NC1=CC=C(C(N)=O)C=C1 VEPLCBIWJQEWSM-UHFFFAOYSA-N 0.000 claims description 2
YPFGLZQCUOYDCU-UHFFFAOYSA-N 4-methoxy-3-[[4-[(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound COC1=CC=C(S(N)(=O)=O)C=C1NC1=NC=CC(NC=2C=C3NN=C(C)C3=CC=2)=N1 YPFGLZQCUOYDCU-UHFFFAOYSA-N 0.000 claims description 2
BMWDAHJEDVUJGK-UHFFFAOYSA-N 4-methoxy-n-[3-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]phenyl]benzenesulfonamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)NC1=CC=CC(NC=2N=C(C=CN=2)N(C)C=2C=C3NN=C(C)C3=CC=2)=C1 BMWDAHJEDVUJGK-UHFFFAOYSA-N 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
YDHRSWAPJJCSGX-UHFFFAOYSA-N n-[3-[[4-[ethyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]phenyl]acetamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(CC)C(N=1)=CC=NC=1NC1=CC=CC(NC(C)=O)=C1 YDHRSWAPJJCSGX-UHFFFAOYSA-N 0.000 claims description 2
RBENAORRCGKTLF-UHFFFAOYSA-N n-[3-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]phenyl]methanesulfonamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=CC=NC=1NC1=CC=CC(NS(C)(=O)=O)=C1 RBENAORRCGKTLF-UHFFFAOYSA-N 0.000 claims description 2
CCDZAMNZEXREEV-UHFFFAOYSA-N n-[[3-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]phenyl]methyl]methanesulfonamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=CC=NC=1NC1=CC=CC(CNS(C)(=O)=O)=C1 CCDZAMNZEXREEV-UHFFFAOYSA-N 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
JPVADQPGSWZOAV-UHFFFAOYSA-N 3-[[4-[(2,3-dimethylindazol-6-yl)-methylamino]-1,3,5-triazin-2-yl]amino]benzenesulfonamide Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=NC=NC=1NC1=CC=CC(S(N)(=O)=O)=C1 JPVADQPGSWZOAV-UHFFFAOYSA-N 0.000 claims 1
DSWWZJMZQVRSAG-UHFFFAOYSA-N 3-[[5-fluoro-4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]-n-propan-2-ylbenzenesulfonamide Chemical compound CC(C)NS(=O)(=O)C1=CC=CC(NC=2N=C(C(F)=CN=2)N(C)C=2C=C3NN=C(C)C3=CC=2)=C1 DSWWZJMZQVRSAG-UHFFFAOYSA-N 0.000 claims 1
VGKRYNBKIWPPLR-UHFFFAOYSA-N 4-methyl-3-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=CC=NC=1NC1=CC(S(N)(=O)=O)=CC=C1C VGKRYNBKIWPPLR-UHFFFAOYSA-N 0.000 claims 1
RXYIYUOOCZCTQP-UHFFFAOYSA-N 5-methylpyrimidine-2,4-diamine Chemical compound CC1=CN=C(N)N=C1N RXYIYUOOCZCTQP-UHFFFAOYSA-N 0.000 claims 1
125000003944 tolyl group Chemical group 0.000 claims 1
238000000034 method Methods 0.000 abstract description 28
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 19
201000010099 disease Diseases 0.000 abstract description 8
229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 abstract description 3
150000003230 pyrimidines Chemical class 0.000 abstract description 3
229940091171 VEGFR-2 tyrosine kinase inhibitor Drugs 0.000 abstract 1
230000003463 hyperproliferative effect Effects 0.000 abstract 1
238000001819 mass spectrum Methods 0.000 description 92
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 54
239000000543 intermediate Substances 0.000 description 49
239000000243 solution Substances 0.000 description 48
238000005481 NMR spectroscopy Methods 0.000 description 46
239000000203 mixture Substances 0.000 description 46
239000007787 solid Substances 0.000 description 42
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 37
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
235000002639 sodium chloride Nutrition 0.000 description 36
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
235000019439 ethyl acetate Nutrition 0.000 description 28
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
238000003786 synthesis reaction Methods 0.000 description 26
230000015572 biosynthetic process Effects 0.000 description 25
102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 22
239000011541 reaction mixture Substances 0.000 description 21
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 20
230000000694 effects Effects 0.000 description 19
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
239000000047 product Substances 0.000 description 18
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 14
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 14
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 14
230000033115 angiogenesis Effects 0.000 description 14
230000002829 reductive effect Effects 0.000 description 14
239000000741 silica gel Substances 0.000 description 14
229910002027 silica gel Inorganic materials 0.000 description 14
239000002904 solvent Substances 0.000 description 14
239000000725 suspension Substances 0.000 description 14
102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
239000000843 powder Substances 0.000 description 12
239000002244 precipitate Substances 0.000 description 12
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 11
208000035475 disorder Diseases 0.000 description 11
239000003112 inhibitor Substances 0.000 description 11
238000010992 reflux Methods 0.000 description 11
WHPFEQUEHBULBW-UHFFFAOYSA-N 2,4-dichloro-5-fluoropyrimidine Chemical compound FC1=CN=C(Cl)N=C1Cl WHPFEQUEHBULBW-UHFFFAOYSA-N 0.000 description 10
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
239000012044 organic layer Substances 0.000 description 10
238000004809 thin layer chromatography Methods 0.000 description 10
238000005160 1H NMR spectroscopy Methods 0.000 description 9
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
239000004480 active ingredient Substances 0.000 description 9
238000000746 purification Methods 0.000 description 9
229910052938 sodium sulfate Inorganic materials 0.000 description 9
235000011152 sodium sulphate Nutrition 0.000 description 9
239000003826 tablet Substances 0.000 description 9
OMRXVBREYFZQHU-UHFFFAOYSA-N 2,4-dichloro-1,3,5-triazine Chemical compound ClC1=NC=NC(Cl)=N1 OMRXVBREYFZQHU-UHFFFAOYSA-N 0.000 description 8
BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 8
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
108091008605 VEGF receptors Proteins 0.000 description 8
230000002159 abnormal effect Effects 0.000 description 8
239000002246 antineoplastic agent Substances 0.000 description 8
125000004432 carbon atom Chemical group C* 0.000 description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
235000017557 sodium bicarbonate Nutrition 0.000 description 8
238000003756 stirring Methods 0.000 description 8
238000006467 substitution reaction Methods 0.000 description 8
102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 7
230000002491 angiogenic effect Effects 0.000 description 7
210000002889 endothelial cell Anatomy 0.000 description 7
238000001914 filtration Methods 0.000 description 7
239000000463 material Substances 0.000 description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 7
GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 6
241000124008 Mammalia Species 0.000 description 6
229960000583 acetic acid Drugs 0.000 description 6
150000001448 anilines Chemical class 0.000 description 6
229940034982 antineoplastic agent Drugs 0.000 description 6
210000004027 cell Anatomy 0.000 description 6
239000000284 extract Substances 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
125000000623 heterocyclic group Chemical group 0.000 description 6
150000003840 hydrochlorides Chemical class 0.000 description 6
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
238000010898 silica gel chromatography Methods 0.000 description 6
HWSCSUHNTVVKSR-UHFFFAOYSA-N 3-methyl-2h-indazol-6-amine Chemical compound NC1=CC=C2C(C)=NNC2=C1 HWSCSUHNTVVKSR-UHFFFAOYSA-N 0.000 description 5
108091000080 Phosphotransferase Proteins 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 5
230000001594 aberrant effect Effects 0.000 description 5
230000002411 adverse Effects 0.000 description 5
230000022131 cell cycle Effects 0.000 description 5
238000000576 coating method Methods 0.000 description 5
239000006071 cream Substances 0.000 description 5
239000006196 drop Substances 0.000 description 5
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
239000007788 liquid Substances 0.000 description 5
239000000314 lubricant Substances 0.000 description 5
239000002609 medium Substances 0.000 description 5
239000003921 oil Substances 0.000 description 5
239000012071 phase Substances 0.000 description 5
102000020233 phosphotransferase Human genes 0.000 description 5
230000008569 process Effects 0.000 description 5
239000000126 substance Substances 0.000 description 5
125000001424 substituent group Chemical group 0.000 description 5
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 5
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
239000004215 Carbon black (E152) Substances 0.000 description 4
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
230000004913 activation Effects 0.000 description 4
230000006978 adaptation Effects 0.000 description 4
230000029936 alkylation Effects 0.000 description 4
238000005804 alkylation reaction Methods 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
239000002585 base Substances 0.000 description 4
239000011230 binding agent Substances 0.000 description 4
239000002775 capsule Substances 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
239000011248 coating agent Substances 0.000 description 4
239000012043 crude product Substances 0.000 description 4
238000006073 displacement reaction Methods 0.000 description 4
230000006870 function Effects 0.000 description 4
239000008187 granular material Substances 0.000 description 4
125000001072 heteroaryl group Chemical group 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
229930195733 hydrocarbon Natural products 0.000 description 4
150000002430 hydrocarbons Chemical class 0.000 description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
231100000252 nontoxic Toxicity 0.000 description 4
230000003000 nontoxic effect Effects 0.000 description 4
102000005962 receptors Human genes 0.000 description 4
108020003175 receptors Proteins 0.000 description 4
230000004044 response Effects 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
239000008107 starch Substances 0.000 description 4
235000019698 starch Nutrition 0.000 description 4
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
JHGRUPGVUMAQQU-UHFFFAOYSA-N 2,3-dimethyl-6-nitroindazole Chemical compound C1=C([N+]([O-])=O)C=CC2=C(C)N(C)N=C21 JHGRUPGVUMAQQU-UHFFFAOYSA-N 0.000 description 3
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 3
JPVKCHIPRSQDKL-UHFFFAOYSA-N 3-aminobenzenesulfonamide Chemical compound NC1=CC=CC(S(N)(=O)=O)=C1 JPVKCHIPRSQDKL-UHFFFAOYSA-N 0.000 description 3
WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
102100022014 Angiopoietin-1 receptor Human genes 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
102100024785 Fibroblast growth factor 2 Human genes 0.000 description 3
108090000379 Fibroblast growth factor 2 Proteins 0.000 description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
239000007995 HEPES buffer Substances 0.000 description 3
101000753291 Homo sapiens Angiopoietin-1 receptor Proteins 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 3
229910021626 Tin(II) chloride Inorganic materials 0.000 description 3
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
239000013543 active substance Substances 0.000 description 3
125000004647 alkyl sulfenyl group Chemical group 0.000 description 3
125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
125000004414 alkyl thio group Chemical group 0.000 description 3
229940100198 alkylating agent Drugs 0.000 description 3
239000002168 alkylating agent Substances 0.000 description 3
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 3
238000011319 anticancer therapy Methods 0.000 description 3
150000004982 aromatic amines Chemical class 0.000 description 3
125000003118 aryl group Chemical group 0.000 description 3
239000012267 brine Substances 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
238000009833 condensation Methods 0.000 description 3
230000005494 condensation Effects 0.000 description 3
230000001419 dependent effect Effects 0.000 description 3
239000007884 disintegrant Substances 0.000 description 3
238000000132 electrospray ionisation Methods 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
239000011737 fluorine Substances 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
229960002949 fluorouracil Drugs 0.000 description 3
235000013355 food flavoring agent Nutrition 0.000 description 3
239000012458 free base Substances 0.000 description 3
239000000499 gel Substances 0.000 description 3
230000012010 growth Effects 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
239000011630 iodine Substances 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
239000010410 layer Substances 0.000 description 3
239000003446 ligand Substances 0.000 description 3
230000003211 malignant effect Effects 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
XEWWOVPHINSRCF-UHFFFAOYSA-N n,3-dimethyl-2h-indazol-6-amine Chemical compound CNC1=CC=C2C(C)=NNC2=C1 XEWWOVPHINSRCF-UHFFFAOYSA-N 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
125000004043 oxo group Chemical group O=* 0.000 description 3
239000006072 paste Substances 0.000 description 3
125000005010 perfluoroalkyl group Chemical group 0.000 description 3
230000026731 phosphorylation Effects 0.000 description 3
238000006366 phosphorylation reaction Methods 0.000 description 3
229920000642 polymer Polymers 0.000 description 3
108090000765 processed proteins & peptides Proteins 0.000 description 3
230000035755 proliferation Effects 0.000 description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
230000009467 reduction Effects 0.000 description 3
230000019491 signal transduction Effects 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
235000011150 stannous chloride Nutrition 0.000 description 3
229940124530 sulfonamide Drugs 0.000 description 3
150000003456 sulfonamides Chemical class 0.000 description 3
239000006188 syrup Substances 0.000 description 3
235000020357 syrup Nutrition 0.000 description 3
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 3
210000001519 tissue Anatomy 0.000 description 3
238000011200 topical administration Methods 0.000 description 3
230000008728 vascular permeability Effects 0.000 description 3
239000001993 wax Substances 0.000 description 3
UJMLVDVWFPOBPP-UHFFFAOYSA-N (2-methyl-6-nitroindazol-3-yl)methanol Chemical compound C1=C([N+]([O-])=O)C=CC2=C(CO)N(C)N=C21 UJMLVDVWFPOBPP-UHFFFAOYSA-N 0.000 description 2
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 2
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 0.000 description 2
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 2
PVNVSSNARYHLRF-UHFFFAOYSA-N 2,3-dimethylindazol-6-amine Chemical compound C1=C(N)C=CC2=C(C)N(C)N=C21 PVNVSSNARYHLRF-UHFFFAOYSA-N 0.000 description 2
MGSXZPZPZIPVHO-UHFFFAOYSA-N 2-[(3-methyl-2h-indazol-6-yl)-[2-[3-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]acetonitrile Chemical compound C=1C=C2C(C)=NNC2=CC=1N(CC#N)C(N=1)=CC=NC=1NC1=CC=CC(CS(C)(=O)=O)=C1 MGSXZPZPZIPVHO-UHFFFAOYSA-N 0.000 description 2
UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical group ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 2
MLPVBIWIRCKMJV-UHFFFAOYSA-N 2-ethylaniline Chemical compound CCC1=CC=CC=C1N MLPVBIWIRCKMJV-UHFFFAOYSA-N 0.000 description 2
KJVBJICWGQIMOZ-UHFFFAOYSA-N 2-fluoro-5-nitroaniline Chemical compound NC1=CC([N+]([O-])=O)=CC=C1F KJVBJICWGQIMOZ-UHFFFAOYSA-N 0.000 description 2
IWSKRHKNENXMHF-UHFFFAOYSA-N 2-methyl-3-(trityloxymethyl)indazol-6-amine Chemical compound CN1N=C2C=C(N)C=CC2=C1COC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 IWSKRHKNENXMHF-UHFFFAOYSA-N 0.000 description 2
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
FJNLCHNQVJVCPY-UHFFFAOYSA-N 2-n-methoxy-2-n-methyl-4-n,6-n-dipropyl-1,3,5-triazine-2,4,6-triamine Chemical compound CCCNC1=NC(NCCC)=NC(N(C)OC)=N1 FJNLCHNQVJVCPY-UHFFFAOYSA-N 0.000 description 2
HNWHYBPWRJLVPL-UHFFFAOYSA-N 3-(bromomethyl)-2-methyl-6-nitroindazole Chemical compound C1=C([N+]([O-])=O)C=CC2=C(CBr)N(C)N=C21 HNWHYBPWRJLVPL-UHFFFAOYSA-N 0.000 description 2
MNHBALCGJBHRKR-UHFFFAOYSA-N 3-[[4-[[3-(hydroxymethyl)-2-methylindazol-6-yl]-methylamino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound C1=CC2=C(CO)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=CC(S(N)(=O)=O)=C1 MNHBALCGJBHRKR-UHFFFAOYSA-N 0.000 description 2
GAPNLOYBMMGLKD-UHFFFAOYSA-N 3-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]benzamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=CC=NC=1NC1=CC=CC(C(N)=O)=C1 GAPNLOYBMMGLKD-UHFFFAOYSA-N 0.000 description 2
FUNWSYKLFDLUIZ-UHFFFAOYSA-N 3-methyl-6-nitro-2h-indazole Chemical compound C1=C([N+]([O-])=O)C=CC2=C(C)NN=C21 FUNWSYKLFDLUIZ-UHFFFAOYSA-N 0.000 description 2
MQUXVJOIFGANRK-UHFFFAOYSA-N 4-chloro-n-[3-(methylsulfonylmethyl)phenyl]-1,3,5-triazin-2-amine Chemical compound CS(=O)(=O)CC1=CC=CC(NC=2N=C(Cl)N=CN=2)=C1 MQUXVJOIFGANRK-UHFFFAOYSA-N 0.000 description 2
229960000549 4-dimethylaminophenol Drugs 0.000 description 2
VPZVZTQEOLCYMQ-UHFFFAOYSA-N 4-methoxy-3-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound COC1=CC=C(S(N)(=O)=O)C=C1NC1=NC=CC(N(C)C=2C=C3NN=C(C)C3=CC=2)=N1 VPZVZTQEOLCYMQ-UHFFFAOYSA-N 0.000 description 2
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
229920001817 Agar Polymers 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
201000001320 Atherosclerosis Diseases 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
102000001301 EGF receptor Human genes 0.000 description 2
108060006698 EGF receptor Proteins 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 description 2
101000851030 Homo sapiens Vascular endothelial growth factor receptor 3 Proteins 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
101100258328 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) crc-2 gene Proteins 0.000 description 2
108091008606 PDGF receptors Proteins 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
208000034038 Pathologic Neovascularization Diseases 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 2
229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
102000001253 Protein Kinase Human genes 0.000 description 2
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 2
102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 2
102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 2
238000002835 absorbance Methods 0.000 description 2
239000002253 acid Substances 0.000 description 2
RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
125000004423 acyloxy group Chemical group 0.000 description 2
230000000996 additive effect Effects 0.000 description 2
239000000443 aerosol Substances 0.000 description 2
235000010419 agar Nutrition 0.000 description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
239000007900 aqueous suspension Substances 0.000 description 2
238000003556 assay Methods 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
210000002469 basement membrane Anatomy 0.000 description 2
235000012216 bentonite Nutrition 0.000 description 2
239000000440 bentonite Substances 0.000 description 2
229910000278 bentonite Inorganic materials 0.000 description 2
SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
239000008280 blood Substances 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
230000037396 body weight Effects 0.000 description 2
GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
239000000872 buffer Substances 0.000 description 2
229910000024 caesium carbonate Inorganic materials 0.000 description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
239000008112 carboxymethyl-cellulose Substances 0.000 description 2
230000000973 chemotherapeutic effect Effects 0.000 description 2
238000002512 chemotherapy Methods 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
238000003776 cleavage reaction Methods 0.000 description 2
239000003086 colorant Substances 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
238000002648 combination therapy Methods 0.000 description 2
239000000470 constituent Substances 0.000 description 2
238000001816 cooling Methods 0.000 description 2
125000004966 cyanoalkyl group Chemical group 0.000 description 2
229940127089 cytotoxic agent Drugs 0.000 description 2
238000011161 development Methods 0.000 description 2
230000018109 developmental process Effects 0.000 description 2
238000010586 diagram Methods 0.000 description 2
150000004985 diamines Chemical class 0.000 description 2
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
LTYMSROWYAPPGB-UHFFFAOYSA-N diphenyl sulfide Chemical compound C=1C=CC=CC=1SC1=CC=CC=C1 LTYMSROWYAPPGB-UHFFFAOYSA-N 0.000 description 2
238000004090 dissolution Methods 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
239000003480 eluent Substances 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
230000002124 endocrine Effects 0.000 description 2
238000011049 filling Methods 0.000 description 2
239000012467 final product Substances 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
239000012530 fluid Substances 0.000 description 2
239000006260 foam Substances 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
230000014509 gene expression Effects 0.000 description 2
238000005469 granulation Methods 0.000 description 2
230000003179 granulation Effects 0.000 description 2
239000003102 growth factor Substances 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
125000005842 heteroatom Chemical group 0.000 description 2
238000002868 homogeneous time resolved fluorescence Methods 0.000 description 2
239000005457 ice water Substances 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
239000007924 injection Substances 0.000 description 2
238000002347 injection Methods 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 2
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
239000002502 liposome Substances 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
238000003760 magnetic stirring Methods 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
238000002156 mixing Methods 0.000 description 2
125000002950 monocyclic group Chemical group 0.000 description 2
230000035772 mutation Effects 0.000 description 2
SCUMWVJJSLLWHQ-UHFFFAOYSA-N n-(2-chloropyrimidin-4-yl)-2,3-dimethylindazol-6-amine Chemical compound C1=CC2=C(C)N(C)N=C2C=C1NC1=CC=NC(Cl)=N1 SCUMWVJJSLLWHQ-UHFFFAOYSA-N 0.000 description 2
DVGMRZQSSNNTFY-UHFFFAOYSA-N n-(2-chloropyrimidin-4-yl)-n,2,3-trimethylindazol-6-amine Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C1=CC=NC(Cl)=N1 DVGMRZQSSNNTFY-UHFFFAOYSA-N 0.000 description 2
AXBKRLMNVZOBIH-UHFFFAOYSA-N n-[3-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]phenyl]acetamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=CC=NC=1NC1=CC=CC(NC(C)=O)=C1 AXBKRLMNVZOBIH-UHFFFAOYSA-N 0.000 description 2
WSOASQNARKHWJC-UHFFFAOYSA-N n-[[4-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]phenyl]methyl]ethanesulfonamide Chemical compound C1=CC(CNS(=O)(=O)CC)=CC=C1NC1=NC=CC(N(C)C=2C=C3NN=C(C)C3=CC=2)=N1 WSOASQNARKHWJC-UHFFFAOYSA-N 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
238000006396 nitration reaction Methods 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
239000002674 ointment Substances 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
230000002018 overexpression Effects 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
239000010452 phosphate Substances 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
238000003825 pressing Methods 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
108060006633 protein kinase Proteins 0.000 description 2
230000005855 radiation Effects 0.000 description 2
238000011160 research Methods 0.000 description 2
230000002441 reversible effect Effects 0.000 description 2
238000012552 review Methods 0.000 description 2
230000007017 scission Effects 0.000 description 2
239000011734 sodium Substances 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
239000007921 spray Substances 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
239000007858 starting material Substances 0.000 description 2
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
150000003457 sulfones Chemical class 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
235000012222 talc Nutrition 0.000 description 2
XGTBHWCPIXKDGI-UHFFFAOYSA-N tert-butyl 6-[(2-chloropyrimidin-4-yl)amino]-3-methylindazole-1-carboxylate Chemical compound C=1C=C2C(C)=NN(C(=O)OC(C)(C)C)C2=CC=1NC1=CC=NC(Cl)=N1 XGTBHWCPIXKDGI-UHFFFAOYSA-N 0.000 description 2
238000012360 testing method Methods 0.000 description 2
229940124597 therapeutic agent Drugs 0.000 description 2
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 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
125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 2
230000005747 tumor angiogenesis Effects 0.000 description 2
239000002691 unilamellar liposome Substances 0.000 description 2
230000029663 wound healing Effects 0.000 description 2
TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
CRYXXTXWUCPIMU-WNQIDUERSA-N (2s)-2-aminobutanediamide;phenol Chemical compound OC1=CC=CC=C1.NC(=O)[C@@H](N)CC(N)=O CRYXXTXWUCPIMU-WNQIDUERSA-N 0.000 description 1
OMJKFYKNWZZKTK-POHAHGRESA-N (5z)-5-(dimethylaminohydrazinylidene)imidazole-4-carboxamide Chemical compound CN(C)N\N=C1/N=CN=C1C(N)=O OMJKFYKNWZZKTK-POHAHGRESA-N 0.000 description 1
GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
FIDRAVVQGKNYQK-UHFFFAOYSA-N 1,2,3,4-tetrahydrotriazine Chemical compound C1NNNC=C1 FIDRAVVQGKNYQK-UHFFFAOYSA-N 0.000 description 1
CRRGPIBVQLNTRN-UHFFFAOYSA-N 1,2-dimethyl-5-nitrobenzimidazole Chemical compound [O-][N+](=O)C1=CC=C2N(C)C(C)=NC2=C1 CRRGPIBVQLNTRN-UHFFFAOYSA-N 0.000 description 1
KHIGSIBNOPKCOT-UHFFFAOYSA-N 1,2-dimethylbenzimidazol-5-amine Chemical compound NC1=CC=C2N(C)C(C)=NC2=C1 KHIGSIBNOPKCOT-UHFFFAOYSA-N 0.000 description 1
VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 1
VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
LZIYAIRGDHSVED-UHFFFAOYSA-N 1-(bromomethyl)-3-chlorobenzene Chemical compound ClC1=CC=CC(CBr)=C1 LZIYAIRGDHSVED-UHFFFAOYSA-N 0.000 description 1
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
YDTDKKULPWTHRV-UHFFFAOYSA-N 1H-indazol-3-amine Chemical compound C1=CC=C2C(N)=NNC2=C1 YDTDKKULPWTHRV-UHFFFAOYSA-N 0.000 description 1
OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
XSGMGAINOILNJR-UHFFFAOYSA-N 2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-methyl-3-tritylsulfanylbutanoic acid Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)NC(C(O)=O)C(C)(C)SC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 XSGMGAINOILNJR-UHFFFAOYSA-N 0.000 description 1
AQOHXZNHZBSPSK-UHFFFAOYSA-N 2-[(3-chlorophenyl)methyl]-n-(2-chloropyrimidin-4-yl)-n,3-dimethylindazol-6-amine Chemical compound C=1C=NC(Cl)=NC=1N(C)C(=CC1=N2)C=CC1=C(C)N2CC1=CC=CC(Cl)=C1 AQOHXZNHZBSPSK-UHFFFAOYSA-N 0.000 description 1
FHXGQQPTQDWUEV-UHFFFAOYSA-N 2-[4-[[4-[(2,3-dimethylindazol-6-yl)-methylamino]pyrimidin-2-yl]amino]phenyl]ethanesulfonamide Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(CCS(N)(=O)=O)C=C1 FHXGQQPTQDWUEV-UHFFFAOYSA-N 0.000 description 1
JWYUFVNJZUSCSM-UHFFFAOYSA-N 2-aminobenzimidazole Chemical compound C1=CC=C2NC(N)=NC2=C1 JWYUFVNJZUSCSM-UHFFFAOYSA-N 0.000 description 1
URJRMNVBDMPCSI-UHFFFAOYSA-N 2-benzyl-1-methyl-5-nitrobenzimidazole Chemical compound N=1C2=CC([N+]([O-])=O)=CC=C2N(C)C=1CC1=CC=CC=C1 URJRMNVBDMPCSI-UHFFFAOYSA-N 0.000 description 1
125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 1
MMZWMCKTKJKIMC-UHFFFAOYSA-N 2-ethyl-5-nitroaniline Chemical compound CCC1=CC=C([N+]([O-])=O)C=C1N MMZWMCKTKJKIMC-UHFFFAOYSA-N 0.000 description 1
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
HVAPQIDOYHNFCN-UHFFFAOYSA-N 2-methoxy-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=CC=C1OC HVAPQIDOYHNFCN-UHFFFAOYSA-N 0.000 description 1
DCPPLBUZAPJHML-UHFFFAOYSA-N 2-methyl-6-nitro-3-(trityloxymethyl)indazole Chemical compound CN1N=C2C=C([N+]([O-])=O)C=CC2=C1COC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 DCPPLBUZAPJHML-UHFFFAOYSA-N 0.000 description 1
OPJKGTJXHVPYIM-UHFFFAOYSA-N 2-methylprop-2-enamide;phenol Chemical compound CC(=C)C(N)=O.OC1=CC=CC=C1 OPJKGTJXHVPYIM-UHFFFAOYSA-N 0.000 description 1
ALQFBYVDVDYXAA-UHFFFAOYSA-N 2-n-(5-ethylsulfonyl-2-methoxyphenyl)-4-n-(3-methyl-2h-indazol-6-yl)pyrimidine-2,4-diamine Chemical compound CCS(=O)(=O)C1=CC=C(OC)C(NC=2N=C(NC=3C=C4NN=C(C)C4=CC=3)C=CN=2)=C1 ALQFBYVDVDYXAA-UHFFFAOYSA-N 0.000 description 1
KRTDQDCPEZRVGC-UHFFFAOYSA-N 2-nitro-1h-benzimidazole Chemical compound C1=CC=C2NC([N+](=O)[O-])=NC2=C1 KRTDQDCPEZRVGC-UHFFFAOYSA-N 0.000 description 1
MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
GECSZAKQFLIPNJ-UHFFFAOYSA-N 3-(methylsulfonylmethyl)aniline Chemical compound CS(=O)(=O)CC1=CC=CC(N)=C1 GECSZAKQFLIPNJ-UHFFFAOYSA-N 0.000 description 1
FUUMHDABRAONFV-UHFFFAOYSA-N 3-[[4-[(1,2-dimethylbenzimidazol-5-yl)-methylamino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound C=1C=C2N(C)C(C)=NC2=CC=1N(C)C(N=1)=CC=NC=1NC1=CC=CC(S(N)(=O)=O)=C1 FUUMHDABRAONFV-UHFFFAOYSA-N 0.000 description 1
RVEFFVNYSWZPRS-UHFFFAOYSA-N 3-[[4-[(2-ethyl-3-methylindazol-6-yl)-methylamino]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound C1=CC2=C(C)N(CC)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=CC(S(N)(=O)=O)=C1 RVEFFVNYSWZPRS-UHFFFAOYSA-N 0.000 description 1
ZKRVEZQWDFOFJY-UHFFFAOYSA-N 3-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]benzenesulfonamide;hydrochloride Chemical compound Cl.C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=CC=NC=1NC1=CC=CC(S(N)(=O)=O)=C1 ZKRVEZQWDFOFJY-UHFFFAOYSA-N 0.000 description 1
IBCFYVDVAYYIBT-UHFFFAOYSA-N 3-[[5-fluoro-4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]-4-methoxy-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC)C(NC=2N=C(C(F)=CN=2)N(C)C=2C=C3NN=C(C)C3=CC=2)=C1 IBCFYVDVAYYIBT-UHFFFAOYSA-N 0.000 description 1
HUFJHZSBLKYZBE-UHFFFAOYSA-N 3-[[5-fluoro-4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]-4-methoxy-n-propan-2-ylbenzenesulfonamide Chemical compound COC1=CC=C(S(=O)(=O)NC(C)C)C=C1NC1=NC=C(F)C(N(C)C=2C=C3NN=C(C)C3=CC=2)=N1 HUFJHZSBLKYZBE-UHFFFAOYSA-N 0.000 description 1
KLDLRDSRCMJKGM-UHFFFAOYSA-N 3-[chloro-(2-oxo-1,3-oxazolidin-3-yl)phosphoryl]-1,3-oxazolidin-2-one Chemical compound C1COC(=O)N1P(=O)(Cl)N1CCOC1=O KLDLRDSRCMJKGM-UHFFFAOYSA-N 0.000 description 1
HCZDHXMDYWZPPN-UHFFFAOYSA-N 3-amino-4-methylbenzenesulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1N HCZDHXMDYWZPPN-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
AYCUWHKQKJDCOS-UHFFFAOYSA-N 3-methyl-2h-indazol-6-amine;hydrochloride Chemical compound Cl.NC1=CC=C2C(C)=NNC2=C1 AYCUWHKQKJDCOS-UHFFFAOYSA-N 0.000 description 1
AZMNTGQGAOYERI-UHFFFAOYSA-N 3-methyl-6-nitro-7h-indazole Chemical compound C1C([N+]([O-])=O)=CC=C2C(C)=NN=C21 AZMNTGQGAOYERI-UHFFFAOYSA-N 0.000 description 1
OWIRCRREDNEXTA-UHFFFAOYSA-N 3-nitro-1h-indazole Chemical class C1=CC=C2C([N+](=O)[O-])=NNC2=C1 OWIRCRREDNEXTA-UHFFFAOYSA-N 0.000 description 1
AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
NRAGRPIQSKNAQS-UHFFFAOYSA-N 4-(2,3-dimethylindazol-6-yl)-4-N-methyl-2-N-[4-(methylsulfonylmethyl)phenyl]-1H-pyrimidine-2,4-diamine Chemical compound CN1N=C2C=C(C=CC2=C1C)C1(NC(=NC=C1)NC1=CC=C(C=C1)CS(=O)(=O)C)NC NRAGRPIQSKNAQS-UHFFFAOYSA-N 0.000 description 1
125000004539 5-benzimidazolyl group Chemical group N1=CNC2=C1C=CC(=C2)* 0.000 description 1
XDLWNEUYUGKDTC-UHFFFAOYSA-N 5-ethylsulfonyl-2-methoxyaniline Chemical compound CCS(=O)(=O)C1=CC=C(OC)C(N)=C1 XDLWNEUYUGKDTC-UHFFFAOYSA-N 0.000 description 1
AQRABUUXKQANHS-UHFFFAOYSA-N 5-fluoro-4-n-methyl-4-n-(3-methyl-2h-indazol-6-yl)-2-n-[3-(propan-2-ylsulfonylmethyl)phenyl]pyrimidine-2,4-diamine Chemical compound CC(C)S(=O)(=O)CC1=CC=CC(NC=2N=C(C(F)=CN=2)N(C)C=2C=C3NN=C(C)C3=CC=2)=C1 AQRABUUXKQANHS-UHFFFAOYSA-N 0.000 description 1
WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 1
ORZRMRUXSPNQQL-UHFFFAOYSA-N 6-nitro-1h-indazole Chemical class [O-][N+](=O)C1=CC=C2C=NNC2=C1 ORZRMRUXSPNQQL-UHFFFAOYSA-N 0.000 description 1
FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
FUXVKZWTXQUGMW-FQEVSTJZSA-N 9-Aminocamptothecin Chemical compound C1=CC(N)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 FUXVKZWTXQUGMW-FQEVSTJZSA-N 0.000 description 1
OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
206010006187 Breast cancer Diseases 0.000 description 1
208000026310 Breast neoplasm Diseases 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
PBIKYEXGTLNUIF-UHFFFAOYSA-N CC1=C2C=CC(=CC2=NN1)NC3=NC(=NC=C3F)N(C)C4=CC=CC(=C4)CS(=O)(=O)C(C)C Chemical compound CC1=C2C=CC(=CC2=NN1)NC3=NC(=NC=C3F)N(C)C4=CC=CC(=C4)CS(=O)(=O)C(C)C PBIKYEXGTLNUIF-UHFFFAOYSA-N 0.000 description 1
YFGGIHRZNWSTIN-UHFFFAOYSA-N COOC(C)(OOC)OOC Chemical compound COOC(C)(OOC)OOC YFGGIHRZNWSTIN-UHFFFAOYSA-N 0.000 description 1
DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 1
101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
206010063209 Chronic allograft nephropathy Diseases 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
HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
102000012422 Collagen Type I Human genes 0.000 description 1
108010022452 Collagen Type I Proteins 0.000 description 1
206010009944 Colon cancer Diseases 0.000 description 1
102000016736 Cyclin Human genes 0.000 description 1
108050006400 Cyclin Proteins 0.000 description 1
108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 description 1
108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 1
102100036239 Cyclin-dependent kinase 2 Human genes 0.000 description 1
102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 1
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
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 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
108010092160 Dactinomycin Proteins 0.000 description 1
WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
208000007342 Diabetic Nephropathies Diseases 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 description 1
238000002965 ELISA Methods 0.000 description 1
101100001675 Emericella variicolor andJ gene Proteins 0.000 description 1
241000792859 Enema Species 0.000 description 1
HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
241000920033 Eugenes Species 0.000 description 1
108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
206010015866 Extravasation Diseases 0.000 description 1
102000009123 Fibrin Human genes 0.000 description 1
108010073385 Fibrin Proteins 0.000 description 1
BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
241000206672 Gelidium Species 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
108010069236 Goserelin Proteins 0.000 description 1
102000009465 Growth Factor Receptors Human genes 0.000 description 1
108010009202 Growth Factor Receptors Proteins 0.000 description 1
229910004373 HOAc Inorganic materials 0.000 description 1
108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
102100021866 Hepatocyte growth factor Human genes 0.000 description 1
101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
206010021143 Hypoxia Diseases 0.000 description 1
XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 1
206010025538 Malignant ascites Diseases 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
FGOFNVXHDGQVBG-UHFFFAOYSA-N N-(2-methoxyphenyl)acetamide Chemical compound COC1=CC=CC=C1NC(C)=O FGOFNVXHDGQVBG-UHFFFAOYSA-N 0.000 description 1
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
238000007126 N-alkylation reaction Methods 0.000 description 1
ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
150000001204 N-oxides Chemical class 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
206010029113 Neovascularisation Diseases 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-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
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
229930012538 Paclitaxel Natural products 0.000 description 1
229930040373 Paraformaldehyde Natural products 0.000 description 1
YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 1
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
108010039918 Polylysine Proteins 0.000 description 1
229920001710 Polyorthoester Polymers 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
102100024028 Progonadoliberin-1 Human genes 0.000 description 1
102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
102100037787 Protein-tyrosine kinase 2-beta Human genes 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 1
102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
206010038923 Retinopathy Diseases 0.000 description 1
206010038934 Retinopathy proliferative Diseases 0.000 description 1
229910005965 SO 2 Inorganic materials 0.000 description 1
229920001800 Shellac Polymers 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 1
229920002253 Tannate Polymers 0.000 description 1
YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
208000034841 Thrombotic Microangiopathies Diseases 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
206010052779 Transplant rejections Diseases 0.000 description 1
102000004504 Urokinase Plasminogen Activator Receptors Human genes 0.000 description 1
108010042352 Urokinase Plasminogen Activator Receptors Proteins 0.000 description 1
102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 1
102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 description 1
JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
229940122803 Vinca alkaloid Drugs 0.000 description 1
238000002441 X-ray diffraction Methods 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
239000002250 absorbent Substances 0.000 description 1
230000002745 absorbent Effects 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
239000008272 agar Substances 0.000 description 1
239000000556 agonist Substances 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
229940072056 alginate Drugs 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 description 1
229960003459 allopurinol Drugs 0.000 description 1
229960000473 altretamine Drugs 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
238000005576 amination reaction Methods 0.000 description 1
125000000539 amino acid group Chemical group 0.000 description 1
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
229960002932 anastrozole Drugs 0.000 description 1
YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 1
239000002870 angiogenesis inducing agent 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
150000001450 anions Chemical class 0.000 description 1
230000008485 antagonism Effects 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000002280 anti-androgenic effect Effects 0.000 description 1
230000001093 anti-cancer Effects 0.000 description 1
229940124650 anti-cancer therapies Drugs 0.000 description 1
229940046836 anti-estrogen Drugs 0.000 description 1
230000001833 anti-estrogenic effect Effects 0.000 description 1
230000000340 anti-metabolite Effects 0.000 description 1
230000000118 anti-neoplastic effect Effects 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
239000000051 antiandrogen Substances 0.000 description 1
229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
229940100197 antimetabolite Drugs 0.000 description 1
239000002256 antimetabolite Substances 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
239000011260 aqueous acid Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
239000003886 aromatase inhibitor Substances 0.000 description 1
229940046844 aromatase inhibitors Drugs 0.000 description 1
125000003435 aroyl group Chemical group 0.000 description 1
125000005333 aroyloxy group Chemical group 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
239000008122 artificial sweetener Substances 0.000 description 1
235000021311 artificial sweeteners Nutrition 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
230000035578 autophosphorylation Effects 0.000 description 1
VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
239000000022 bacteriostatic agent Substances 0.000 description 1
RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
125000001743 benzylic group Chemical group 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
229960000997 bicalutamide Drugs 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
229920002988 biodegradable polymer Polymers 0.000 description 1
239000004621 biodegradable polymer Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
229920001400 block copolymer Polymers 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
201000008275 breast carcinoma Diseases 0.000 description 1
229960002092 busulfan Drugs 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
235000013539 calcium stearate Nutrition 0.000 description 1
239000008116 calcium stearate Substances 0.000 description 1
MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
229940127093 camptothecin Drugs 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
229960004562 carboplatin Drugs 0.000 description 1
229940105329 carboxymethylcellulose Drugs 0.000 description 1
229960005243 carmustine Drugs 0.000 description 1
239000000969 carrier Substances 0.000 description 1
229960000590 celecoxib Drugs 0.000 description 1
RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
230000010261 cell growth Effects 0.000 description 1
230000004663 cell proliferation Effects 0.000 description 1
238000001516 cell proliferation assay Methods 0.000 description 1
238000000451 chemical ionisation Methods 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
229960004630 chlorambucil Drugs 0.000 description 1
WGXZDYPGLJYBJW-UHFFFAOYSA-N chloroform;propan-2-ol Chemical compound CC(C)O.ClC(Cl)Cl WGXZDYPGLJYBJW-UHFFFAOYSA-N 0.000 description 1
238000005957 chlorosulfonylation reaction Methods 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
208000037976 chronic inflammation Diseases 0.000 description 1
208000037893 chronic inflammatory disorder Diseases 0.000 description 1
208000019425 cirrhosis of liver Diseases 0.000 description 1
229960004316 cisplatin Drugs 0.000 description 1
DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
229940090805 clavulanate Drugs 0.000 description 1
HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
238000004140 cleaning Methods 0.000 description 1
239000008119 colloidal silica Substances 0.000 description 1
210000001072 colon Anatomy 0.000 description 1
JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
229920001577 copolymer Polymers 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
229960004397 cyclophosphamide Drugs 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
229960000978 cyproterone acetate Drugs 0.000 description 1
UWFYSQMTEOIJJG-FDTZYFLXSA-N cyproterone acetate Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 UWFYSQMTEOIJJG-FDTZYFLXSA-N 0.000 description 1
229960000684 cytarabine Drugs 0.000 description 1
231100000433 cytotoxic Toxicity 0.000 description 1
230000001472 cytotoxic effect Effects 0.000 description 1
229960003901 dacarbazine Drugs 0.000 description 1
229960000640 dactinomycin Drugs 0.000 description 1
STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 1
230000008021 deposition Effects 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
238000001514 detection method Methods 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
208000033679 diabetic kidney disease Diseases 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
238000006471 dimerization reaction Methods 0.000 description 1
239000001177 diphosphate Substances 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
239000002270 dispersing agent Substances 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
150000004141 diterpene derivatives Chemical class 0.000 description 1
GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 1
229960003668 docetaxel Drugs 0.000 description 1
POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
229960004679 doxorubicin Drugs 0.000 description 1
229950004203 droloxifene Drugs 0.000 description 1
238000007876 drug discovery Methods 0.000 description 1
239000000975 dye Substances 0.000 description 1
229940009662 edetate Drugs 0.000 description 1
229950005627 embonate Drugs 0.000 description 1
230000013020 embryo development Effects 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000007920 enema Substances 0.000 description 1
229940079360 enema for constipation Drugs 0.000 description 1
229960001904 epirubicin Drugs 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
229950000206 estolate Drugs 0.000 description 1
239000000328 estrogen antagonist Substances 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
229960005420 etoposide Drugs 0.000 description 1
230000005284 excitation Effects 0.000 description 1
229960000255 exemestane Drugs 0.000 description 1
210000002744 extracellular matrix Anatomy 0.000 description 1
230000036251 extravasation Effects 0.000 description 1
239000003889 eye drop Substances 0.000 description 1
229940012356 eye drops Drugs 0.000 description 1
238000010265 fast atom bombardment Methods 0.000 description 1
229950003499 fibrin Drugs 0.000 description 1
230000003176 fibrotic effect Effects 0.000 description 1
DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 1
229960004039 finasteride Drugs 0.000 description 1
239000010419 fine particle Substances 0.000 description 1
ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 1
150000005699 fluoropyrimidines Chemical class 0.000 description 1
MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
229960002074 flutamide Drugs 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
229940050411 fumarate Drugs 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
239000011521 glass Substances 0.000 description 1
229960001731 gluceptate Drugs 0.000 description 1
KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
239000008103 glucose Substances 0.000 description 1
229930195712 glutamate Natural products 0.000 description 1
229940049906 glutamate Drugs 0.000 description 1
XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 1
229960003690 goserelin acetate Drugs 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
235000015220 hamburgers Nutrition 0.000 description 1
201000005787 hematologic cancer Diseases 0.000 description 1
208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000003054 hormonal effect Effects 0.000 description 1
XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
239000000017 hydrogel Substances 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
239000008309 hydrophilic cream Substances 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
230000007954 hypoxia Effects 0.000 description 1
229960000908 idarubicin Drugs 0.000 description 1
230000003116 impacting effect Effects 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
229960004768 irinotecan Drugs 0.000 description 1
208000023589 ischemic disease Diseases 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
238000002955 isolation Methods 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
229940001447 lactate Drugs 0.000 description 1
229940099584 lactobionate Drugs 0.000 description 1
JYTUSYBCFIZPBE-AMTLMPIISA-M lactobionate Chemical compound [O-]C(=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-M 0.000 description 1
229940070765 laurate Drugs 0.000 description 1
229960003881 letrozole Drugs 0.000 description 1
HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
238000011068 loading method Methods 0.000 description 1
229960002247 lomustine Drugs 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
229940049920 malate Drugs 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical compound [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 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
IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
OCSMOTCMPXTDND-OUAUKWLOSA-N marimastat Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)[C@H](CC(C)C)[C@H](O)C(=O)NO OCSMOTCMPXTDND-OUAUKWLOSA-N 0.000 description 1
229950008959 marimastat Drugs 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
229960004961 mechlorethamine Drugs 0.000 description 1
229960004296 megestrol acetate Drugs 0.000 description 1
RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
229960001924 melphalan Drugs 0.000 description 1
239000001525 mentha piperita l. herb oil Substances 0.000 description 1
GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
229960001428 mercaptopurine Drugs 0.000 description 1
210000003584 mesangial cell Anatomy 0.000 description 1
208000030159 metabolic disease Diseases 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
239000003475 metalloproteinase inhibitor Substances 0.000 description 1
229960000485 methotrexate Drugs 0.000 description 1
229940102396 methyl bromide Drugs 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
229960004857 mitomycin Drugs 0.000 description 1
239000003068 molecular probe Substances 0.000 description 1
239000002324 mouth wash Substances 0.000 description 1
229940051866 mouthwash Drugs 0.000 description 1
BXGTVNLGPMZLAZ-UHFFFAOYSA-N n'-ethylmethanediimine;hydrochloride Chemical compound Cl.CCN=C=N BXGTVNLGPMZLAZ-UHFFFAOYSA-N 0.000 description 1
CNUIFIIXYRSXPF-UHFFFAOYSA-N n-(2-chloro-5-fluoropyrimidin-4-yl)-3-methyl-2h-indazol-6-amine Chemical compound C=1C=C2C(C)=NNC2=CC=1NC1=NC(Cl)=NC=C1F CNUIFIIXYRSXPF-UHFFFAOYSA-N 0.000 description 1
OLFYOLGKLZDRGT-UHFFFAOYSA-N n-(2-chloropyrimidin-4-yl)-n,1,2-trimethylbenzimidazol-5-amine Chemical compound C=1C=C2N(C)C(C)=NC2=CC=1N(C)C1=CC=NC(Cl)=N1 OLFYOLGKLZDRGT-UHFFFAOYSA-N 0.000 description 1
YBPAAAOPILYQDC-UHFFFAOYSA-N n-(2-chloropyrimidin-4-yl)-n,3-dimethyl-2h-indazol-6-amine Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C1=CC=NC(Cl)=N1 YBPAAAOPILYQDC-UHFFFAOYSA-N 0.000 description 1
BLCLNMBMMGCOAS-UHFFFAOYSA-N n-[1-[[1-[[1-[[1-[[1-[[1-[[1-[2-[(carbamoylamino)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amin Chemical compound C1CCC(C(=O)NNC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)C(COC(C)(C)C)NC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 BLCLNMBMMGCOAS-UHFFFAOYSA-N 0.000 description 1
FHCXJZSNEBTJKE-UHFFFAOYSA-N n-[2-methyl-5-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]-1,3,5-triazin-2-yl]amino]phenyl]methanesulfonamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=NC=NC=1NC1=CC=C(C)C(NS(C)(=O)=O)=C1 FHCXJZSNEBTJKE-UHFFFAOYSA-N 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
QBZQUILLPPLIMU-UHFFFAOYSA-N n-[4-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]-1,3,5-triazin-2-yl]amino]phenyl]acetamide;hydrochloride Chemical compound Cl.C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=NC=NC=1NC1=CC=C(NC(C)=O)C=C1 QBZQUILLPPLIMU-UHFFFAOYSA-N 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
XGXNTJHZPBRBHJ-UHFFFAOYSA-N n-phenylpyrimidin-2-amine Chemical compound N=1C=CC=NC=1NC1=CC=CC=C1 XGXNTJHZPBRBHJ-UHFFFAOYSA-N 0.000 description 1
239000007923 nasal drop Substances 0.000 description 1
229940100662 nasal drops Drugs 0.000 description 1
229940097496 nasal spray Drugs 0.000 description 1
239000007922 nasal spray Substances 0.000 description 1
235000021096 natural sweeteners Nutrition 0.000 description 1
239000013642 negative control Substances 0.000 description 1
230000035407 negative regulation of cell proliferation Effects 0.000 description 1
201000009925 nephrosclerosis Diseases 0.000 description 1
230000004770 neurodegeneration Effects 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 description 1
229960002653 nilutamide Drugs 0.000 description 1
125000006574 non-aromatic ring group Chemical group 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000003883 ointment base Substances 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
229960003552 other antineoplastic agent in atc Drugs 0.000 description 1
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
229960001756 oxaliplatin Drugs 0.000 description 1
DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
229960001592 paclitaxel Drugs 0.000 description 1
125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229940014662 pantothenate Drugs 0.000 description 1
235000019161 pantothenic acid Nutrition 0.000 description 1
239000011713 pantothenic acid Substances 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
229920002866 paraformaldehyde Polymers 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000002245 particle Substances 0.000 description 1
239000011236 particulate material Substances 0.000 description 1
235000010603 pastilles Nutrition 0.000 description 1
235000019477 peppermint oil Nutrition 0.000 description 1
210000004786 perivascular cell Anatomy 0.000 description 1
239000008177 pharmaceutical agent Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
229960003424 phenylacetic acid Drugs 0.000 description 1
239000003279 phenylacetic acid Substances 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
150000008105 phosphatidylcholines Chemical class 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
229960003171 plicamycin Drugs 0.000 description 1
238000005498 polishing Methods 0.000 description 1
229920000747 poly(lactic acid) Polymers 0.000 description 1
229920002721 polycyanoacrylate Polymers 0.000 description 1
239000004626 polylactic acid Substances 0.000 description 1
229920000656 polylysine Polymers 0.000 description 1
229920006324 polyoxymethylene Polymers 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
230000026341 positive regulation of angiogenesis Effects 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
QPMDWIOUHQWKHV-ODZAUARKSA-M potassium;(z)-4-hydroxy-4-oxobut-2-enoate Chemical compound [K+].OC(=O)\C=C/C([O-])=O QPMDWIOUHQWKHV-ODZAUARKSA-M 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
230000002265 prevention Effects 0.000 description 1
230000001023 pro-angiogenic effect Effects 0.000 description 1
230000009443 proangiogenesis Effects 0.000 description 1
230000006482 proangiogenic pathway Effects 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
239000000583 progesterone congener Substances 0.000 description 1
229940095055 progestogen systemic hormonal contraceptives Drugs 0.000 description 1
230000002062 proliferating effect Effects 0.000 description 1
239000011253 protective coating Substances 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
238000010298 pulverizing process Methods 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical compound NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 description 1
238000001959 radiotherapy Methods 0.000 description 1
229960004622 raloxifene Drugs 0.000 description 1
GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
230000007115 recruitment Effects 0.000 description 1
230000009703 regulation of cell differentiation Effects 0.000 description 1
230000021014 regulation of cell growth Effects 0.000 description 1
230000008521 reorganization Effects 0.000 description 1
230000001850 reproductive effect Effects 0.000 description 1
208000037803 restenosis Diseases 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
239000004576 sand Substances 0.000 description 1
238000009991 scouring Methods 0.000 description 1
239000004208 shellac Substances 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
102000034285 signal transducing proteins Human genes 0.000 description 1
108091006024 signal transducing proteins Proteins 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
ABBQHOQBGMUPJH-UHFFFAOYSA-N sodium;2-hydroxybenzoic acid Chemical compound [Na+].OC(=O)C1=CC=CC=C1O ABBQHOQBGMUPJH-UHFFFAOYSA-N 0.000 description 1
YNBRSWNUNPAQOF-UHFFFAOYSA-M sodium;phenylmethanesulfonate Chemical compound [Na+].[O-]S(=O)(=O)CC1=CC=CC=C1 YNBRSWNUNPAQOF-UHFFFAOYSA-M 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000001119 stannous chloride Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
229960002317 succinimide Drugs 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
125000004646 sulfenyl group Chemical group S(*)* 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
XTQHKBHJIVJGKJ-UHFFFAOYSA-N sulfur monoxide Chemical class S=O XTQHKBHJIVJGKJ-UHFFFAOYSA-N 0.000 description 1
229910052815 sulfur oxide Inorganic materials 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
230000002195 synergetic effect Effects 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
229960001603 tamoxifen Drugs 0.000 description 1
230000008685 targeting Effects 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
229960001278 teniposide Drugs 0.000 description 1
229950002757 teoclate Drugs 0.000 description 1
DHHKPEUQJIEKOA-UHFFFAOYSA-N tert-butyl 2-[6-(nitromethyl)-6-bicyclo[3.2.0]hept-3-enyl]acetate Chemical compound C1C=CC2C(CC(=O)OC(C)(C)C)(C[N+]([O-])=O)CC21 DHHKPEUQJIEKOA-UHFFFAOYSA-N 0.000 description 1
HNKXDUWDVLHDOB-UHFFFAOYSA-N tert-butyl 6-[(2-chloro-5-fluoropyrimidin-4-yl)-methylamino]-3-methylindazole-1-carboxylate Chemical compound C=1C=C2C(C)=NN(C(=O)OC(C)(C)C)C2=CC=1N(C)C1=NC(Cl)=NC=C1F HNKXDUWDVLHDOB-UHFFFAOYSA-N 0.000 description 1
ICQWBNUSYDNQEP-UHFFFAOYSA-N tert-butyl 6-[(2-chloro-5-fluoropyrimidin-4-yl)amino]-3-methylindazole-1-carboxylate Chemical compound C=1C=C2C(C)=NN(C(=O)OC(C)(C)C)C2=CC=1NC1=NC(Cl)=NC=C1F ICQWBNUSYDNQEP-UHFFFAOYSA-N 0.000 description 1
BQFWUQIBPHWZBA-UHFFFAOYSA-N tert-butyl 6-[(2-chloropyrimidin-4-yl)-methylamino]-3-methylindazole-1-carboxylate Chemical compound C=1C=C2C(C)=NN(C(=O)OC(C)(C)C)C2=CC=1N(C)C1=CC=NC(Cl)=N1 BQFWUQIBPHWZBA-UHFFFAOYSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
239000012414 tert-butyl nitrite Substances 0.000 description 1
229960003604 testosterone Drugs 0.000 description 1
RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
150000003536 tetrazoles Chemical class 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 description 1
229960003087 tioguanine Drugs 0.000 description 1
230000008467 tissue growth Effects 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
229940100611 topical cream Drugs 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
229940100615 topical ointment Drugs 0.000 description 1
XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
229960005026 toremifene Drugs 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
238000012546 transfer Methods 0.000 description 1
108091008578 transmembrane receptors Proteins 0.000 description 1
102000027257 transmembrane receptors Human genes 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
WRTMQOHKMFDUKX-UHFFFAOYSA-N triiodide Chemical compound I[I-]I WRTMQOHKMFDUKX-UHFFFAOYSA-N 0.000 description 1
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
210000003606 umbilical vein Anatomy 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
210000005166 vasculature Anatomy 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
229960004528 vincristine Drugs 0.000 description 1
OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
HHJUWIANJFBDHT-KOTLKJBCSA-N vindesine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(N)=O)N4C)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 HHJUWIANJFBDHT-KOTLKJBCSA-N 0.000 description 1
229960004355 vindesine Drugs 0.000 description 1
GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
229960002066 vinorelbine Drugs 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
239000000230 xanthan gum Substances 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
229920001285 xanthan gum Polymers 0.000 description 1
229940082509 xanthan gum Drugs 0.000 description 1
229930195724 β-lactose Natural products 0.000 description 1
PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/30—Halogen atoms or nitro radicals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/10—Ophthalmic agents for accommodation disorders, e.g. myopia
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

NO20032831A 2000-12-21 2003-06-20 Pyrimidinaminer, anvendelse derav samt farmasoytisk preparat. NO325987B1 (no)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US25752600P	2000-12-21	2000-12-21
US26240301P	2001-01-16	2001-01-16
PCT/US2001/049367 WO2002059110A1 (en)	2000-12-21	2001-12-19	Pyrimidineamines as angiogenesis modulators

Publications (3)

Publication Number	Publication Date
NO20032831D0 NO20032831D0 (no)	2003-06-20
NO20032831L NO20032831L (no)	2003-08-15
NO325987B1 true NO325987B1 (no)	2008-08-25

Family

ID=26946028

Family Applications (3)

Application Number	Title	Priority Date	Filing Date
NO20032831A NO325987B1 (no)	2000-12-21	2003-06-20	Pyrimidinaminer, anvendelse derav samt farmasoytisk preparat.
NO2010020C NO2010020I1 (no)	2000-12-21	2010-11-10	5-{{4-[(2,3-dimetyl-2H-indazot-6-yl)(metyl)amino]pyrimidin-2-yl}amino)-2-metylbenzensulfonamid Pazopanib.
NO2022001C NO2022001I1 (no)	2000-12-21	2022-01-06	Pazopanib

Family Applications After (2)

Application Number	Title	Priority Date	Filing Date
NO2010020C NO2010020I1 (no)	2000-12-21	2010-11-10	5-{{4-[(2,3-dimetyl-2H-indazot-6-yl)(metyl)amino]pyrimidin-2-yl}amino)-2-metylbenzensulfonamid Pazopanib.
NO2022001C NO2022001I1 (no)	2000-12-21	2022-01-06	Pazopanib

Country Status (28)

Country	Link
US (6)	US7105530B2 (de)
EP (2)	EP2311825B1 (de)
JP (1)	JP4253188B2 (de)
KR (1)	KR100847169B1 (de)
CN (1)	CN1307173C (de)
AT (1)	ATE430742T1 (de)
AU (1)	AU2002246723B2 (de)
BE (1)	BE2010C030I2 (de)
BR (1)	BR0116452A (de)
CA (1)	CA2432000C (de)
CY (2)	CY1109160T1 (de)
CZ (1)	CZ304059B6 (de)
DE (2)	DE122010000038I1 (de)
DK (2)	DK2311825T3 (de)
ES (2)	ES2324981T3 (de)
FR (1)	FR10C0037I2 (de)
HK (2)	HK1059926A1 (de)
HU (2)	HU230574B1 (de)
IL (2)	IL156306A0 (de)
LU (1)	LU91710I2 (de)
MX (1)	MXPA03005696A (de)
NO (3)	NO325987B1 (de)
NZ (1)	NZ526542A (de)
PL (1)	PL214667B1 (de)
PT (2)	PT1343782E (de)
SI (2)	SI2311825T1 (de)
WO (1)	WO2002059110A1 (de)
ZA (1)	ZA200304482B (de)

Families Citing this family (226)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2001060816A1 (en) *	2000-02-17	2001-08-23	Amgen Inc.	Kinase inhibitors
ATE430742T1 (de) *	2000-12-21	2009-05-15	Smithkline Beecham Corp	Pyrimidinamine als angiogenesemodulatoren
US7153871B2 (en)	2001-01-22	2006-12-26	Memory Pharmaceuticals Corporation	Phosphodiesterase 4 inhibitors, including aminoindazole and aminobenzofuran analogs
US7205320B2 (en)	2001-01-22	2007-04-17	Memory Pharmaceuticals Corp.	Phosphodiesterase 4 inhibitors
CA2451128A1 (en)	2001-06-26	2003-01-09	Bristol-Myers Squibb Company	N-heterocyclic inhibitors of tnf-alpha expression
US7115617B2 (en)	2001-08-22	2006-10-03	Amgen Inc.	Amino-substituted pyrimidinyl derivatives and methods of use
US6939874B2 (en) *	2001-08-22	2005-09-06	Amgen Inc.	Substituted pyrimidinyl derivatives and methods of use
EP2090571B1 (de) *	2001-10-17	2012-05-16	Boehringer Ingelheim Pharma GmbH & Co. KG	Pyrimidinderivate, Arzneimittel enthaltend diese Verbindungen, deren Verwendung und Verfahren zu ihrer Herstellung
MXPA04004176A (es) *	2001-11-01	2004-09-06	Janssen Pharmaceutica Nv	Derivados de aminobenzamida como inhibidores de cinasa 3beta de glicogeno sintasa.
TWI329105B (en)	2002-02-01	2010-08-21	Rigel Pharmaceuticals Inc	2,4-pyrimidinediamine compounds and their uses
ES2290479T3 (es)	2002-03-01	2008-02-16	Smithkline Beecham Corporation	Diamino-pirimidinas y su uso como inhibidores de la angiogenesis.
CA2489648A1 (en) *	2002-06-17	2003-12-24	Smithkline Beecham Corporation	Chemical process
RU2354648C2 (ru) *	2002-07-19	2009-05-10	Мемори Фармасьютиклз Корпорейшн	Соединения 6-амино-1н-индазола и 4-аминобензофурана в качестве ингибиторов фосфодиэстеразы 4
JP2006504656A (ja)	2002-07-19	2006-02-09	メモリー・ファーマシューティカルズ・コーポレイション	Ｎ−置換されたアニリン及びジフェニルアミンアナログを含むホスホジエステラーゼ４インヒビター
US7517886B2 (en) *	2002-07-29	2009-04-14	Rigel Pharmaceuticals, Inc.	Methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds
AU2003287178A1 (en) *	2002-10-10	2004-05-04	Smithkline Beecham Corporation	Chemical compounds
AU2003295656B2 (en)	2002-11-19	2010-11-11	Memory Pharmaceuticals Corporation	Pyridine N-oxide compounds as phosphodiesterase 4 inhibitors
UA80767C2 (en) *	2002-12-20	2007-10-25	Pfizer Prod Inc	Pyrimidine derivatives for the treatment of abnormal cell growth
WO2004056807A1 (en)	2002-12-20	2004-07-08	Pfizer Products Inc.	Pyrimidine derivatives for the treatment of abnormal cell growth
US7109337B2 (en)	2002-12-20	2006-09-19	Pfizer Inc	Pyrimidine derivatives for the treatment of abnormal cell growth
US20040167132A1 (en) *	2003-01-16	2004-08-26	Geetha Shankar	Methods of treating conditions associted with an Edg-2 receptor
ES2325440T3 (es)	2003-02-20	2009-09-04	Smithkline Beecham Corporation	Compuestos de pirimidina.
JP5105874B2 (ja)	2003-07-18	2012-12-26	アムジエン・インコーポレーテツド	肝細胞増殖因子に対する特異的結合因子
CN102358738A (zh)	2003-07-30	2012-02-22	里格尔药品股份有限公司	2,4-嘧啶二胺化合物及其预防和治疗自体免疫疾病的用途
DE602004032446D1 (de) *	2003-08-07	2011-06-09	Rigel Pharmaceuticals Inc	2,4-pyrimidindiamin-verbindungen und verwendungen als antiproliferative mittel
CA2544591A1 (en) *	2003-11-06	2005-05-26	Celgene Corporation	Methods of using and compositions comprising a jnk inhibitor for the treatment and management of asbestos-related diseases and disorders
US20070208023A1 (en) *	2004-04-16	2007-09-06	Smithkline Beecham Corporation	Cancer Treatment Method
BRPI0511132A (pt)	2004-05-14	2007-11-27	Pfizer Prod Inc	derivados de pirimidina e composição farmacêutica compreendendo os mesmos
WO2005111016A1 (en)	2004-05-14	2005-11-24	Pfizer Products Inc.	Pyrimidine derivatives for the treatment of abnormal cell growth
BRPI0510980A (pt)	2004-05-14	2007-11-27	Pfizer Prod Inc	derivados de pirimidina para o tratamento do crescimento anormal de células
CA2566531A1 (en)	2004-05-18	2005-12-15	Rigel Pharmaceuticals, Inc.	Cycloalkyl substituted pyrimidinediamine compounds and their uses
WO2006020564A1 (en) *	2004-08-09	2006-02-23	Smithkline Beecham Corporation	Pyrimidin derivatives for the treatment of multiple myeloma
AU2005295788A1 (en) *	2004-10-13	2006-04-27	Wyeth	N-benzenesulfonyl substituted anilino-pyrimidine analogs
GB2420559B (en)	2004-11-15	2008-08-06	Rigel Pharmaceuticals Inc	Stereoisomerically enriched 3-aminocarbonyl bicycloheptene pyrimidinediamine compounds and their uses
CN100516049C (zh)	2004-11-16	2009-07-22	永信药品工业股份有限公司	抗血管生成药n2-(取代的芳基甲基)-3-(取代的苯基)吲唑的合成
CA2584295C (en)	2004-11-24	2014-08-26	Rigel Pharmaceuticals, Inc.	Spiro-2, 4-pyrimidinediamine compounds and their uses
EP1827434B1 (de)	2004-11-30	2014-01-15	Amgen Inc.	Chinolin- und chinazolinanaloge und deren verwendung als medikamente zur krebsbehandlung
DE602006010979D1 (de)	2005-01-19	2010-01-21	Rigel Pharmaceuticals Inc	Prodrugs aus 2,4-pyrimidindiamin-verbindungen und ihre verwendungen
US8227455B2 (en)	2005-04-18	2012-07-24	Rigel Pharmaceuticals, Inc.	Methods of treating cell proliferative disorders
WO2006129100A1 (en) *	2005-06-03	2006-12-07	Glaxo Group Limited	Novel compounds
US20070203161A1 (en) *	2006-02-24	2007-08-30	Rigel Pharmaceuticals, Inc.	Compositions and methods for inhibition of the jak pathway
WO2006133426A2 (en) *	2005-06-08	2006-12-14	Rigel Pharmaceuticals, Inc.	Compositions and methods for inhibition of the jak pathway
WO2007042504A2 (fr)	2005-10-07	2007-04-19	Guerbet	Composes comprenant une partie de reconnaissance d'une cible biologique, couplee a une partie de signal capable de complexer le gallium
US8986650B2 (en)	2005-10-07	2015-03-24	Guerbet	Complex folate-NOTA-Ga68
DE602006020611D1 (de)	2005-11-29	2011-04-21	Glaxosmithkline Llc	Krebsbehandlungsverfahren
MX2008006379A (es) *	2005-11-29	2009-03-03	Smithkline Beecham Corp	Metodo de tratamiento.
US20080108664A1 (en)	2005-12-23	2008-05-08	Liu Belle B	Solid-state form of AMG 706 and pharmaceutical compositions thereof
TW200736232A (en) *	2006-01-26	2007-10-01	Astrazeneca Ab	Pyrimidine derivatives
AR059066A1 (es)	2006-01-27	2008-03-12	Amgen Inc	Combinaciones del inhibidor de la angiopoyetina -2 (ang2) y el inhibidor del factor de crecimiento endotelial vascular (vegf)
AU2007212696B2 (en)	2006-02-10	2011-05-19	Amgen Inc.	Hydrate forms of AMG706
CA2642229C (en)	2006-02-24	2015-05-12	Rigel Pharmaceuticals, Inc.	Compositions and methods for inhibition of the jak pathway
WO2007143483A2 (en) *	2006-06-01	2007-12-13	Smithkline Beecham Corporation	Combination of pazopanib and lapatinib for treating cancer
PE20121506A1 (es)	2006-07-14	2012-11-26	Amgen Inc	Compuestos triazolopiridinas como inhibidores de c-met
US8217177B2 (en)	2006-07-14	2012-07-10	Amgen Inc.	Fused heterocyclic derivatives and methods of use
WO2008049123A2 (en)	2006-10-19	2008-04-24	Rigel Pharmaceuticals, Inc.	2,4-pyrimidinediamine derivatives as inhibitors of jak kinases for the treatment of autoimmune diseases
AU2007338792B2 (en)	2006-12-20	2012-05-31	Amgen Inc.	Substituted heterocycles and methods of use
US7759344B2 (en)	2007-01-09	2010-07-20	Amgen Inc.	Bis-aryl amide derivatives and methods of use
FR2911604B1 (fr)	2007-01-19	2009-04-17	Sanofi Aventis Sa	Derives de n-(heteroaryl-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique
WO2008103277A2 (en)	2007-02-16	2008-08-28	Amgen Inc.	Nitrogen-containing heterocyclyl ketones and their use as c-met inhibitors
WO2008128231A1 (en) *	2007-04-16	2008-10-23	Hutchison Medipharma Enterprises Limited	Pyrimidine derivatives
CL2008002444A1 (es)	2007-08-21	2009-09-04	Amgen Inc	Anticuerpo o fragmento del mismo que se une a la proteina c-fms humana; molecula de acido nucleico que la codifica; vector y celula huesped; metodo de elaboracion; composicion farmaceutica que la comprende; y su uso para tratar o prevenir una condicion asociada con c-fms en un paciente.
EP2058307A1 (de)	2007-11-12	2009-05-13	Cellzome Ag	Verfahren zur Identifizierung von mit JAK-Kinase wechselwirkenden Molekülen und zur JAK-Kinase-Reinigung
KR20170051521A (ko)	2008-04-16	2017-05-11	포톨라 파마슈티컬스, 인코포레이티드	ｓｙｋ 또는 ＪＡＫ 키나제 억제제로서의 ２,６－디아미노-피리미딘－５－일－카르복스아미드
US8138339B2 (en)	2008-04-16	2012-03-20	Portola Pharmaceuticals, Inc.	Inhibitors of protein kinases
NZ589315A (en)	2008-04-16	2012-11-30	Portola Pharm Inc	2,6-diamino-pyrimidin-5-yl-carboxamides as Spleen tryosine kinase (syk) or Janus kinase (JAK) inhibitors
EP2271631B1 (de)	2008-04-22	2018-07-04	Portola Pharmaceuticals, Inc.	Inhibitoren von proteinkinasen
CA2723961C (en)	2008-05-21	2017-03-21	Ariad Pharmaceuticals, Inc.	Phosphorous derivatives as kinase inhibitors
US9273077B2 (en)	2008-05-21	2016-03-01	Ariad Pharmaceuticals, Inc.	Phosphorus derivatives as kinase inhibitors
US20100029689A1 (en) *	2008-07-02	2010-02-04	Memory Pharmaceuticals Corporation	Phosphodiesterase 4 inhibitors
WO2010036796A1 (en) *	2008-09-26	2010-04-01	Concert Pharmaceuticals, Inc.	Pyridineamine derivatives
FR2942227B1 (fr)	2009-02-13	2011-04-15	Guerbet Sa	Utilisation de tampons pour la complexation de radionucleides
US20120232102A1 (en)	2009-09-30	2012-09-13	Chun-Fang Xu	Methods Of Administration And Treatment
WO2011050159A1 (en) *	2009-10-23	2011-04-28	Glaxo Wellcome Manufacturing Pte Ltd	Compositions and processes
WO2011058179A1 (en)	2009-11-16	2011-05-19	Ratiopharm Gmbh	5- (4- (n- (2, 3 -dimethyl- 2h- indazol- 6 -yl) -n-methylamino) pyrimidin- 2 -ylamino) -2 -methylbenzenesulfonamide
WO2011069053A1 (en)	2009-12-04	2011-06-09	Teva Pharmaceutical Industries Ltd.	Process for the preparation of pazopanip hcl and crystalline forms of pazopanib hcl
TW201201808A (en) *	2010-01-06	2012-01-16	Glaxo Wellcome Mfg Pte Ltd	Treatment method
US10166142B2 (en)	2010-01-29	2019-01-01	Forsight Vision4, Inc.	Small molecule delivery with implantable therapeutic device
US8598156B2 (en)	2010-03-25	2013-12-03	Glaxosmithkline Llc	Chemical compounds
AU2011254550B2 (en)	2010-05-21	2013-11-07	Noviga Research Ab	Novel pyrimidine derivatives
EP2575460A4 (de) *	2010-05-26	2013-10-16	Glaxosmithkline Llc	Kombination
CA2797947C (en)	2010-06-04	2019-07-09	Charles Baker-Glenn	Aminopyrimidine derivatives as lrrk2 modulators
WO2011161217A2 (en)	2010-06-23	2011-12-29	Palacký University in Olomouc	Targeting of vegfr2
US20130165456A1 (en)	2010-08-26	2013-06-27	Tona M. Gilmer	Combination
EP2616057A4 (de) *	2010-09-14	2014-03-12	Glaxosmithkline Ip No 2 Ltd	Kombination aus braf- und vegf-hemmern
CA2810900A1 (en) *	2010-10-14	2012-04-19	Ariad Pharmaceuticals, Inc.	Methods for inhibiting cell proliferation in egfr-driven cancers
US8846928B2 (en)	2010-11-01	2014-09-30	Portola Pharmaceuticals, Inc.	Benzamides and nicotinamides as Syk modulators
US20130317029A1 (en)	2010-11-01	2013-11-28	Portola Pharmaceuticals, Inc.	Oxypyrimidines as syk modulators
EP2635557A2 (de)	2010-11-01	2013-09-11	Portola Pharmaceuticals, Inc.	Nicotinamide als jak-kinasemodulatoren
HUE046617T2 (hu)	2010-11-10	2020-03-30	Genentech Inc	Pirazol-aminopirimidin-származékok mint LRRK2 modulátorok
CA2818612C (en)	2010-11-19	2020-12-29	Forsight Vision4, Inc.	Therapeutic agent formulations for implanted devices
WO2012073254A1 (en)	2010-11-29	2012-06-07	Hetero Research Foundation	A process for the preparation of pazopanib using novel intermediate
CN102093340B (zh) *	2010-12-09	2013-07-17	天津药物研究院	2-甲基吲唑衍生物的制备及用途
CN102060848B (zh) *	2010-12-09	2013-09-18	天津药物研究院	芳香胺取代的嘧啶衍生物的制备及用途
CN102093339B (zh) *	2010-12-09	2013-06-12	天津药物研究院	一类嘧啶衍生物的制备及用途
WO2012082337A2 (en)	2010-12-17	2012-06-21	Glaxo Wellcome Manufacturing Pte Ltd	Combination
FR2968999B1 (fr)	2010-12-20	2013-01-04	Guerbet Sa	Nanoemulsion de chelate pour irm
EP2672969A4 (de)	2011-02-01	2014-07-16	Glaxosmithkline Intellectual Property Ltd	Kombination
DK2688887T3 (en)	2011-03-23	2015-06-29	Amgen Inc	DEHYDRATED tricyclic DUALINHIBITORER OF CDK 4/6 AND FLT3
CA2830129C (en)	2011-03-24	2016-07-19	Chemilia Ab	Novel pyrimidine derivatives
US8916557B2 (en) *	2011-04-19	2014-12-23	Bayer Intellectual Property Gmbh	Substituted 4-Aryl-N-phenyl-1,3,5-triazin-2-amines
CN103501612B (zh)	2011-05-04	2017-03-29	阿里亚德医药股份有限公司	抑制表皮生长因子受体导致的癌症中细胞增殖的化合物
TWI555737B (zh) *	2011-05-24	2016-11-01	拜耳知識產權公司	含有硫醯亞胺基團之４－芳基－ｎ－苯基－１，３，５－三氮雜苯－２－胺
US9745288B2 (en)	2011-08-16	2017-08-29	Indiana University Research And Technology Corporation	Compounds and methods for treating cancer by inhibiting the urokinase receptor
US9133171B2 (en) *	2011-09-16	2015-09-15	Bayer Intellectual Property Gmbh	Disubstituted 5-fluoro pyrimidine derivatives containing a sulfoximine group
FR2980364B1 (fr)	2011-09-26	2018-08-31	Guerbet	Nanoemulsions et leur utilisation comme agents de contraste
IN2014CN02850A (de)	2011-10-31	2015-07-03	Glaxosmithkline Intellectual Property Ltd
IN2014CN04065A (de)	2011-11-23	2015-09-04	Portola Pharm Inc
CN103159742B (zh) *	2011-12-16	2015-08-12	北京韩美药品有限公司	5-氯嘧啶类化合物及其作为egfr酪氨酸激酶抑制剂的应用
AR090263A1 (es)	2012-03-08	2014-10-29	Hoffmann La Roche	Terapia combinada de anticuerpos contra el csf-1r humano y las utilizaciones de la misma
CN103373989B (zh) *	2012-04-28	2016-04-13	上海医药工业研究院	盐酸帕唑帕尼的中间体的制备方法
WO2013169401A1 (en)	2012-05-05	2013-11-14	Ariad Pharmaceuticals, Inc.	Compounds for inhibiting cell proliferation in egfr-driven cancers
US9505749B2 (en)	2012-08-29	2016-11-29	Amgen Inc.	Quinazolinone compounds and derivatives thereof
WO2014058921A2 (en)	2012-10-08	2014-04-17	Portola Pharmaceuticals, Inc.	Substituted pyrimidinyl kinase inhibitors
CA2888383A1 (en)	2012-10-18	2014-04-24	Bayer Pharma Aktiengesellschaft	N-(pyridin-2-yl)pyrimidin-4-amine derivatives containing a sulfone group
CA2888371C (en)	2012-10-18	2021-06-08	Ulrich Lucking	5-fluoro-n-(pyridin-2-yl)pyridin-2-amine derivatives containing a sulfone group
KR102242871B1 (ko)	2012-11-15	2021-04-20	바이엘 파마 악티엔게젤샤프트	술폭시민 기를 함유하는 5-플루오로-n-(피리딘-2-일)피리딘-2-아민 유도체
TW201418243A (zh)	2012-11-15	2014-05-16	Bayer Pharma AG	含有磺醯亞胺基團之ｎ－（吡啶－２－基）嘧啶－４－胺衍生物
CN103864764A (zh) *	2012-12-11	2014-06-18	齐鲁制药有限公司	吲唑取代的嘧啶胺衍生物、其制备方法和用途
EP2935250B1 (de) *	2012-12-17	2018-03-28	Sun Pharmaceutical Industries Limited	Verfahren zur herstellung von pazopanib oder salzen davon
WO2014097152A1 (en)	2012-12-17	2014-06-26	Ranbaxy Laboratories Limited	Process for the preparation of pazopanib or salts thereof
CN103910716A (zh) *	2013-01-07	2014-07-09	华东理工大学	2,4-二取代-环烷基[d]嘧啶类化合物及其用途
JP2016504409A (ja)	2013-01-09	2016-02-12	グラクソスミスクライン、インテレクチュアル、プロパティー、ナンバー２、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅＩｎｔｅｌｌｅｃｔｕａｌＰｒｏｐｅｒｔｙＮｏ．２Ｌｉｍｉｔｅｄ	組合せ
FR3001154B1 (fr)	2013-01-23	2015-06-26	Guerbet Sa	Magneto-emulsion vectorisee
AU2014236455B2 (en)	2013-03-14	2018-07-12	Forsight Vision4, Inc.	Systems for sustained intraocular delivery of low solubility compounds from a port delivery system implant
US9611283B1 (en)	2013-04-10	2017-04-04	Ariad Pharmaceuticals, Inc.	Methods for inhibiting cell proliferation in ALK-driven cancers
CN103214467B (zh) *	2013-04-26	2015-09-30	中国人民解放军军事医学科学院微生物流行病研究所	5-[[4-[(2,3-二甲基-2h-吲唑-6-基)甲氨基]-2嘧啶基]氨基]-2-甲基-苯磺酰胺衍生物及其制备方法与应用
CA2917096C (en)	2013-07-04	2021-05-18	Bayer Pharma Aktiengesellschaft	Sulfoximine substituted 5-fluoro-n-(pyridin-2-yl)pyridin-2-amine derivatives and their use as cdk9 kinase inhibitors
ES2813877T3 (es)	2013-08-28	2021-03-25	Crown Bioscience Inc Taicang	Distintivos de expresión génica predictivos de la respuesta de un sujeto a un inhibidor multicinasa y métodos de uso de los mismos
WO2015056180A1 (en)	2013-10-15	2015-04-23	Glaxosmithkline Intellectual Property (No.2) Limited	Indoline derivatives as inhibitors of perk
WO2015068175A2 (en)	2013-11-05	2015-05-14	Laurus Labs Private Limited	An improved process for the preparation of pazopanib or a pharmaceutically acceptable salt thereof
CN103739550B (zh) *	2014-01-02	2016-06-01	中国药科大学	2,3-二甲基-6-脲-2h-吲唑类化合物及其制备方法与应用
CN104829542B (zh) *	2014-02-10	2018-02-02	中国科学院上海药物研究所	苯胺嘧啶类化合物、其制备方法和医药用途
WO2015136463A1 (en)	2014-03-11	2015-09-17	Glaxosmithkline Intellectual Property (No.2) Limited	Chemical compounds acting as perk inhibitors
US9856242B2 (en)	2014-03-13	2018-01-02	Bayer Pharma Aktiengesellscaft	5-fluoro-N-(pyridin-2-yl)pyridin-2-amine derivatives containing a sulfone group
US9790189B2 (en)	2014-04-01	2017-10-17	Bayer Pharma Aktiengesellschaft	Disubstituted 5-fluoro pyrimidine derivatives containing a sulfondiimine group
CN106459084B (zh)	2014-04-11	2019-04-19	拜耳医药股份有限公司	大环化合物
US9856263B2 (en)	2014-04-28	2018-01-02	Pfizer Inc.	Heteroaromatic compounds and their use as dopamine D1 ligands
MY182793A (en)	2014-08-08	2021-02-05	Forsight Vision4 Inc	Stable and soluble formulations of receptor tyrosine kinase inhibitors, and methods of preparation thereof
WO2016055935A1 (en)	2014-10-06	2016-04-14	Glaxosmithkline Intellectual Property (No.2) Limited	Combination of lysine-specific demethylase 1 inhibitor and thrombopoietin agonist
CN107207475A (zh)	2014-10-16	2017-09-26	拜耳医药股份有限公司	含有砜基团的氟化苯并呋喃基‑嘧啶衍生物
EP3207038B1 (de)	2014-10-16	2018-08-22	Bayer Pharma Aktiengesellschaft	Fluorierte benzofuranyl-pyrimidin-derivate mit einer sulfoximingruppe
EP3242934B1 (de)	2015-01-08	2021-08-18	The Board of Trustees of the Leland Stanford Junior University	Faktoren und zellen zur bereitstellung der induktion von knochen, knochenmark und knorpel
WO2016114322A1 (ja)	2015-01-13	2016-07-21	国立大学法人京都大学	筋萎縮性側索硬化症の予防及び／又は治療剤
KR101705980B1 (ko) *	2015-06-12	2017-02-13	중앙대학교 산학협력단	신규 파조파닙 유도체 및 이를 함유하는 약학조성물
CN105237523B (zh) *	2015-10-08	2018-06-01	深圳市博圣康生物科技有限公司	嘧啶衍生物及其制备方法、用途
WO2017098421A1 (en)	2015-12-08	2017-06-15	Glaxosmithkline Intellectual Property Development Limited	Benzothiadiazine compounds
WO2017153952A1 (en)	2016-03-10	2017-09-14	Glaxosmithkline Intellectual Property Development Limited	5-sulfamoyl-2-hydroxybenzamide derivatives
EP3228630A1 (de)	2016-04-07	2017-10-11	IMBA-Institut für Molekulare Biotechnologie GmbH	Kombination eines apelin-antagonisten und angiogeneseinhibitor zur behandlung von krebs
AU2017279027A1 (en)	2016-06-08	2018-12-20	Glaxosmithkline Intellectual Property Development Limited	Chemical Compounds
KR20190015748A (ko)	2016-06-08	2019-02-14	글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드	Atf4 경로 억제제로서의 화학적 화합물
EP3487503A1 (de)	2016-07-20	2019-05-29	GlaxoSmithKline Intellectual Property Development Limited	Isochinolinderivate als perk-inhibitoren
CN110225983A (zh)	2016-12-01	2019-09-10	葛兰素史密斯克莱知识产权发展有限公司	治疗癌症的方法
RS62456B1 (sr)	2016-12-22	2021-11-30	Amgen Inc	Derivati benzizotiazola, izotiazolo[3,4-b]piridina, hinazolina, ftalazina, pirido[2,3-d]piridazina i pirido[2,3-d]pirimidina kao kras g12c inhibitori za tretman raka pluća, pankreasa ili debelog creva
US11426406B2 (en)	2017-02-09	2022-08-30	Georgetown University	Compositions and methods for treating lysosomal storage disorders
CA3057891A1 (en)	2017-03-28	2018-10-04	Bayer Aktiengesellschaft	Novel ptefb inhibiting macrocyclic compounds
ES2900199T3 (es)	2017-03-28	2022-03-16	Bayer Ag	Novedosos compuestos macrocíclicos inhibidores de PTEFB
JP7108018B2 (ja)	2017-04-17	2022-07-27	イエールユニバーシティ	急性肺傷害を処置または予防する化合物、組成物および方法
JOP20190272A1 (ar)	2017-05-22	2019-11-21	Amgen Inc	مثبطات kras g12c وطرق لاستخدامها
WO2018225093A1 (en)	2017-06-07	2018-12-13	Glaxosmithkline Intellectual Property Development Limited	Chemical compounds as atf4 pathway inhibitors
WO2019008507A1 (en)	2017-07-03	2019-01-10	Glaxosmithkline Intellectual Property Development Limited	2- (4-CHLOROPHENOXY) -N - ((1- (2- (4-CHLOROPHENOXY) ETHYNAZETIDIN-3-YL) METHYL) ACETAMIDE DERIVATIVES AND RELATED COMPOUNDS AS INHIBITORS OF ATF4 FOR THE TREATMENT OF CANCER AND D OTHER DISEASES
CN111164069A (zh)	2017-07-03	2020-05-15	葛兰素史密斯克莱知识产权发展有限公司	作为atf4抑制剂用于治疗癌症和其它疾病的n-(3-(2-(4-氯苯氧基)乙酰胺基)双环[1.1.1]戊-1-基)-2-环丁烷-1-甲酰胺衍生物以及相关化合物
WO2019021208A1 (en)	2017-07-27	2019-01-31	Glaxosmithkline Intellectual Property Development Limited	USEFUL INDAZOLE DERIVATIVES AS PERK INHIBITORS
CN107619407B (zh) *	2017-08-10	2019-05-24	山东大学	基于帕唑帕尼结构的hdac和vegfr双靶点抑制剂及其制备方法和应用
UY37866A (es)	2017-09-07	2019-03-29	Glaxosmithkline Ip Dev Ltd	Nuevos compuestos derivados de benzoimidazol sustituidos que reducen la proteína myc (c-myc) en las células e inhiben la histona acetiltransferasa de p300/cbp.
SG11202001499WA (en)	2017-09-08	2020-03-30	Amgen Inc	Inhibitors of kras g12c and methods of using the same
WO2019053617A1 (en)	2017-09-12	2019-03-21	Glaxosmithkline Intellectual Property Development Limited	CHEMICAL COMPOUNDS
AU2019221019A1 (en)	2018-02-13	2020-07-23	Bayer Aktiengesellschaft	Use of 5-Fluoro-4-(4-fluoro-2-methoxyphenyl)-N-{4-[(S-methylsulfonimidoyl)methyl]pyridin-2-yl}pyridin-2-amine for treating diffuse large B-cell lymphoma
WO2019193541A1 (en)	2018-04-06	2019-10-10	Glaxosmithkline Intellectual Property Development Limited	Bicyclic aromatic ring derivatives of formula (i) as atf4 inhibitors
WO2019193540A1 (en)	2018-04-06	2019-10-10	Glaxosmithkline Intellectual Property Development Limited	Heteroaryl derivatives of formula (i) as atf4 inhibitors
WO2019053500A1 (en)	2018-04-17	2019-03-21	Alvogen Malta Operations (Row) Ltd	PHARMACEUTICAL COMPOSITION OF SOLID DOSAGE FORM CONTAINING PAZOPANIB AND PROCESS FOR PREPARING THE SAME
EP3788038B1 (de)	2018-05-04	2023-10-11	Amgen Inc.	Kras-g12c-inhibitoren und verfahren zu deren verwendung
US11045484B2 (en)	2018-05-04	2021-06-29	Amgen Inc.	KRAS G12C inhibitors and methods of using the same
WO2019217691A1 (en)	2018-05-10	2019-11-14	Amgen Inc.	Kras g12c inhibitors for the treatment of cancer
US11096939B2 (en)	2018-06-01	2021-08-24	Amgen Inc.	KRAS G12C inhibitors and methods of using the same
EP3802537A1 (de)	2018-06-11	2021-04-14	Amgen Inc.	Kras-g12c-inhibitoren zur behandlung von krebs
MX2020012261A (es)	2018-06-12	2021-03-31	Amgen Inc	Inhibidores de kras g12c que comprenden un anillo de piperazina y uso de estos en el tratamiento del cancer.
EP3806858A4 (de)	2018-06-15	2022-03-09	Handa Pharmaceuticals, Inc.	Kinaseinhibitorsalze und zusammensetzungen davon
WO2020007822A1 (en)	2018-07-02	2020-01-09	Conservatoire National Des Arts Et Metiers (Cnam)	Bismuth metallic (0) nanoparticles, process of manufacturing and uses thereof
US20210253528A1 (en)	2018-07-09	2021-08-19	Glaxosmithkline Intellectual Property Development Limited	Chemical compounds
WO2020031107A1 (en)	2018-08-08	2020-02-13	Glaxosmithkline Intellectual Property Development Limited	Chemical compounds
JP2020090482A (ja)	2018-11-16	2020-06-11	アムジエン・インコーポレーテツド	Ｋｒａｓｇ１２ｃ阻害剤化合物の重要な中間体の改良合成法
CA3117222A1 (en)	2018-11-19	2020-05-28	Amgen Inc.	Kras g12c inhibitors and methods of using the same
JP7377679B2 (ja)	2018-11-19	2023-11-10	アムジエン・インコーポレーテツド	がん治療のためのｋｒａｓｇ１２ｃ阻害剤及び１種以上の薬学的に活性な追加の薬剤を含む併用療法
MX2021006156A (es)	2018-11-30	2021-09-08	Glaxosmithkline Ip Dev Ltd	Compuestos utiles en la terapia para el vih.
ES2953821T3 (es)	2018-12-20	2023-11-16	Amgen Inc	Inhibidores de KIF18A
MA54547A (fr)	2018-12-20	2022-03-30	Amgen Inc	Amides d'hétéroaryle utiles en tant qu'inhibiteurs de kif18a
MA54546A (fr)	2018-12-20	2022-03-30	Amgen Inc	Amides d'hétéroaryle utiles en tant qu'inhibiteurs de kif18a
PE20211475A1 (es)	2018-12-20	2021-08-05	Amgen Inc	Inhibidores de kif18a
BR112021011894A2 (pt)	2018-12-21	2021-09-08	Daiichi Sankyo Company, Limited	Composição farmacêutica
JP2022522777A (ja)	2019-03-01	2022-04-20	レボリューションメディシンズインコーポレイテッド	二環式ヘテロアリール化合物及びその使用
US20230096028A1 (en)	2019-03-01	2023-03-30	Revolution Medicines, Inc.	Bicyclic heterocyclyl compounds and uses thereof
EP3738593A1 (de)	2019-05-14	2020-11-18	Amgen, Inc	Dosierung von kras-inhibitor zur behandlung von krebserkrankungen
EP3972973A1 (de)	2019-05-21	2022-03-30	Amgen Inc.	Festkörperformen
WO2021018941A1 (en)	2019-07-31	2021-02-04	Glaxosmithkline Intellectual Property Development Limited	Methods of treating cancer
CN114401953A (zh)	2019-08-02	2022-04-26	美国安进公司	Kif18a抑制剂
WO2021026098A1 (en)	2019-08-02	2021-02-11	Amgen Inc.	Kif18a inhibitors
AU2020324963A1 (en)	2019-08-02	2022-02-24	Amgen Inc.	KIF18A inhibitors
US20220372018A1 (en)	2019-08-02	2022-11-24	Amgen Inc.	Kif18a inhibitors
CN110746402B (zh) *	2019-09-21	2021-01-15	温州医科大学	一种2-n-芳基-4-n-芳基-5-氟嘧啶类化合物及其制备方法和应用
WO2021081212A1 (en)	2019-10-24	2021-04-29	Amgen Inc.	Pyridopyrimidine derivatives useful as kras g12c and kras g12d inhibitors in the treatment of cancer
CA3159559A1 (en)	2019-11-04	2021-05-14	Revolution Medicines, Inc.	Ras inhibitors
TW202132314A (zh)	2019-11-04	2021-09-01	美商銳新醫藥公司	Ｒａｓ抑制劑
EP4054719A1 (de)	2019-11-04	2022-09-14	Revolution Medicines, Inc.	Ras-inhibitoren
PE20230249A1 (es)	2019-11-08	2023-02-07	Revolution Medicines Inc	Compuestos de heteroarilo biciclicos y usos de estos
AR120456A1 (es)	2019-11-14	2022-02-16	Amgen Inc	Síntesis mejorada del compuesto inhibidor de g12c de kras
WO2021097212A1 (en)	2019-11-14	2021-05-20	Amgen Inc.	Improved synthesis of kras g12c inhibitor compound
JP2023505100A (ja)	2019-11-27	2023-02-08	レボリューションメディシンズインコーポレイテッド	共有ｒａｓ阻害剤及びその使用
BR112022010086A2 (pt)	2020-01-07	2022-09-06	Revolution Medicines Inc	Dosagem do inibidor de shp2 e métodos de tratamento de câncer
WO2021236935A1 (en)	2020-05-22	2021-11-25	Qx Therapeutics Inc.	Compositions and methods for treating lung injuries associated with viral infections
CN115916194A (zh)	2020-06-18	2023-04-04	锐新医药公司	用于延迟、预防和治疗针对ras抑制剂的获得性抗性的方法
WO2022040446A1 (en)	2020-08-19	2022-02-24	Nanocopoeia, Llc	Amorphous pazopanib particles and pharmaceutical compositions thereof
AU2021344830A1 (en)	2020-09-03	2023-04-06	Revolution Medicines, Inc.	Use of SOS1 inhibitors to treat malignancies with SHP2 mutations
KR20230067635A (ko)	2020-09-15	2023-05-16	레볼루션 메디슨즈, 인크.	암의 치료에서 ras 억제제로서 인돌 유도체
CN117396472A (zh)	2020-12-22	2024-01-12	上海齐鲁锐格医药研发有限公司	Sos1抑制剂及其用途
WO2022235870A1 (en)	2021-05-05	2022-11-10	Revolution Medicines, Inc.	Ras inhibitors for the treatment of cancer
CR20230570A (es)	2021-05-05	2024-01-22	Revolution Medicines Inc	Inhibidores de ras
CN117500811A (zh)	2021-05-05	2024-02-02	锐新医药公司	共价ras抑制剂及其用途
AR127308A1 (es)	2021-10-08	2024-01-10	Revolution Medicines Inc	Inhibidores ras
WO2023081923A1 (en)	2021-11-08	2023-05-11	Frequency Therapeutics, Inc.	Platelet-derived growth factor receptor (pdgfr) alpha inhibitors and uses thereof
TW202340214A (zh)	2021-12-17	2023-10-16	美商健臻公司	做為shp2抑制劑之吡唑并吡𠯤化合物
EP4227307A1 (de)	2022-02-11	2023-08-16	Genzyme Corporation	Pyrazolopyrazinverbindungen als shp2-inhibitoren
WO2023172940A1 (en)	2022-03-08	2023-09-14	Revolution Medicines, Inc.	Methods for treating immune refractory lung cancer
WO2023228095A1 (en)	2022-05-24	2023-11-30	Daiichi Sankyo Company, Limited	Dosage regimen of an anti-cdh6 antibody-drug conjugate
WO2023230541A1 (en)	2022-05-27	2023-11-30	Viiv Healthcare Company	Piperazine derivatives useful in hiv therapy
WO2023240263A1 (en)	2022-06-10	2023-12-14	Revolution Medicines, Inc.	Macrocyclic ras inhibitors
WO2024081916A1 (en)	2022-10-14	2024-04-18	Black Diamond Therapeutics, Inc.	Methods of treating cancers using isoquinoline or 6-aza-quinoline derivatives

Family Cites Families (49)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS5490121A (en)	1977-11-28	1979-07-17	Boettcher Barry	Neutral copper bonded body and antiinflaming agent
US5639752A (en)	1991-11-25	1997-06-17	Pfizer Inc	Indole derivatives
DE69530989T2 (de)	1994-08-13	2004-05-19	Yuhan Corp.	Neue pyrimidinderivate und verfahren zu ihrer herstellung
US5730977A (en)	1995-08-21	1998-03-24	Mitsui Toatsu Chemicals, Inc.	Anti-VEGF human monoclonal antibody
GB9523675D0 (en)	1995-11-20	1996-01-24	Celltech Therapeutics Ltd	Chemical compounds
GB9624482D0 (en)	1995-12-18	1997-01-15	Zeneca Phaema S A	Chemical compounds
TR199801530T2 (xx)	1996-02-13	1998-11-23	Zeneca Limited	VEGF �nhibit�rleri olarak kinazolin t�revleri.
JP4464466B2 (ja)	1996-03-05	2010-05-19	アストラゼネカ・ユーケイ・リミテッド	４―アニリノキナゾリン誘導体
DE19610799C1 (de)	1996-03-19	1997-09-04	Siemens Ag	Zündeinrichtung zum Auslösen eines Rückhaltemittels in einem Kraftfahrzeug
GB9707800D0 (en)	1996-05-06	1997-06-04	Zeneca Ltd	Chemical compounds
GB9622363D0 (en)	1996-10-28	1997-01-08	Celltech Therapeutics Ltd	Chemical compounds
JP2002501532A (ja)	1997-05-30	2002-01-15	メルクエンドカンパニーインコーポレーテッド	新規血管形成阻害薬
ATE368665T1 (de)	1997-08-22	2007-08-15	Astrazeneca Ab	Oxindolylchinazolinderivate als angiogenesehemmer
EP1017682A4 (de)	1997-09-26	2000-11-08	Merck & Co Inc	Neue angiogenese-inhibitoren
WO1999050250A1 (en)	1998-03-27	1999-10-07	Janssen Pharmaceutica N.V.	Hiv inhibiting pyrimidine derivatives
WO1999060630A1 (en)	1998-05-15	1999-11-25	Glaxo Group Limited	Infrared thermography
UA60365C2 (uk)	1998-06-04	2003-10-15	Пфайзер Продактс Інк.	Похідні ізотіазолу, спосіб їх одержання, фармацевтична композиція та спосіб лікування гіперпроліферативного захворювання у ссавця
WO2000002871A1 (en)	1998-07-10	2000-01-20	Merck & Co., Inc.	Novel angiogenesis inhibitors
US6022307A (en)	1998-07-14	2000-02-08	American Cyanamid Company	Substituted dibenzothiophenes having antiangiogenic activity
DE69933680T2 (de)	1998-08-29	2007-08-23	Astrazeneca Ab	Pyrimidine verbindungen
ATE336484T1 (de)	1998-08-29	2006-09-15	Astrazeneca Ab	Pyrimidine verbindungen
AU760020B2 (en)	1998-08-31	2003-05-08	Merck & Co., Inc.	Novel angiogenesis inhibitors
US6316603B1 (en)	1998-09-08	2001-11-13	Agouron Pharmaceuticals, Inc.	Modifications of the VEGF receptor-2 protein and methods of use
US7262201B1 (en)	1998-10-08	2007-08-28	Astrazeneca Ab	Quinazoline derivatives
GB9828511D0 (en) *	1998-12-24	1999-02-17	Zeneca Ltd	Chemical compounds
AU768201B2 (en)	1999-01-22	2003-12-04	Amgen, Inc.	Kinase inhibitors
CZ306810B6 (cs)	1999-02-10	2017-07-19	Astrazeneca Ab	Použití chinazolinového derivátu jako inhibitoru angiogeneze
WO2000052470A1 (fr)	1999-03-04	2000-09-08	Kyowa Hakko Kogyo Co., Ltd.	Moyen de diagnostic et de traitement de la leucemie
GB9905075D0 (en)	1999-03-06	1999-04-28	Zeneca Ltd	Chemical compounds
US6245759B1 (en)	1999-03-11	2001-06-12	Merck & Co., Inc.	Tyrosine kinase inhibitors
GB9907658D0 (en)	1999-04-06	1999-05-26	Zeneca Ltd	Chemical compounds
CO5170501A1 (es)	1999-04-14	2002-06-27	Novartis Ag	AZOLES SUSTITUIDOS UTILES PARA EL TRATAMIENTO DE ENFERMEDADES MEDIADAS POR TNFa eIL-1 Y ENFERMEDADES DEL METABOLISMO OSEO
CO5170498A1 (es) *	1999-05-28	2002-06-27	Abbott Lab	Biaril sulfonamidas son utiles como inhibidores de proliferacion celular
GB9914258D0 (en) *	1999-06-18	1999-08-18	Celltech Therapeutics Ltd	Chemical compounds
US6498165B1 (en)	1999-06-30	2002-12-24	Merck & Co., Inc.	Src kinase inhibitor compounds
GB9918035D0 (en) *	1999-07-30	1999-09-29	Novartis Ag	Organic compounds
GB9919778D0 (en)	1999-08-21	1999-10-27	Zeneca Ltd	Chemical compounds
BR0013899A (pt)	1999-09-10	2003-07-08	Merck & Co Inc	Composto, composição farmacêutica, processos de tratamento ou prevenção de câncer, de uma doença em que a angiogênese esteja implicada, da vascularização retinal, da retinopatia diabética, da degeneração macular relacionada a idade, de doenças inflamatórias, de uma doença ou condições dependentes da tirosina quinase, de patologias associadas com ossos, e, processos para produzir uma composição farmacêutica, e de reduzir ou prevenir dano tecidual em seguida a um evento isquêmico cerebral
JP2003511378A (ja)	1999-10-07	2003-03-25	アムジエン・インコーポレーテツド	トリアジン系キナーゼ阻害薬
SK7402002A3 (en) *	1999-11-29	2002-11-06	Aventis Pharma Sa	Arylamine derivatives and their use as anti-telomerase agent
EP1246823A1 (de)	1999-12-28	2002-10-09	Pharmacopeia, Inc.	Pyrimidin- und triazin kinase-hemmer
WO2001060816A1 (en) *	2000-02-17	2001-08-23	Amgen Inc.	Kinase inhibitors
GB0004888D0 (en)	2000-03-01	2000-04-19	Astrazeneca Uk Ltd	Chemical compounds
GB0004887D0 (en)	2000-03-01	2000-04-19	Astrazeneca Uk Ltd	Chemical compounds
GB0004890D0 (en)	2000-03-01	2000-04-19	Astrazeneca Uk Ltd	Chemical compounds
IL151992A0 (en)	2000-03-31	2003-04-10	Imclone Systems Inc	Treatment of non-solid mammalian tumors with vascular endothelial growth factor receptor antagonists
AU2001292670A1 (en)	2000-09-15	2002-03-26	Vertex Pharmaceuticals Incorporated	Pyrazole compounds useful as protein kinase inhibitors
AUPR213700A0 (en)	2000-12-18	2001-01-25	Biota Scientific Management Pty Ltd	Antiviral agents
ATE430742T1 (de) *	2000-12-21	2009-05-15	Smithkline Beecham Corp	Pyrimidinamine als angiogenesemodulatoren

2001
- 2001-12-19 AT AT01994315T patent/ATE430742T1/de active
- 2001-12-19 HU HUP0400691A patent/HU230574B1/hu active Protection Beyond IP Right Term
- 2001-12-19 EP EP09159138.8A patent/EP2311825B1/de not_active Expired - Lifetime
- 2001-12-19 ES ES01994315T patent/ES2324981T3/es not_active Expired - Lifetime
- 2001-12-19 PT PT01994315T patent/PT1343782E/pt unknown
- 2001-12-19 DE DE122010000038C patent/DE122010000038I1/de active Pending
- 2001-12-19 DK DK09159138.8T patent/DK2311825T3/en active
- 2001-12-19 IL IL15630601A patent/IL156306A0/xx unknown
- 2001-12-19 BR BR0116452-0A patent/BR0116452A/pt active Search and Examination
- 2001-12-19 PL PL363243A patent/PL214667B1/pl unknown
- 2001-12-19 SI SI200131047T patent/SI2311825T1/sl unknown
- 2001-12-19 MX MXPA03005696A patent/MXPA03005696A/es active IP Right Grant
- 2001-12-19 PT PT91591388T patent/PT2311825E/pt unknown
- 2001-12-19 NZ NZ526542A patent/NZ526542A/en not_active IP Right Cessation
- 2001-12-19 KR KR1020037008349A patent/KR100847169B1/ko active IP Right Review Request
- 2001-12-19 EP EP01994315A patent/EP1343782B1/de not_active Expired - Lifetime
- 2001-12-19 CN CNB018227503A patent/CN1307173C/zh not_active Expired - Lifetime
- 2001-12-19 ES ES09159138.8T patent/ES2556946T3/es not_active Expired - Lifetime
- 2001-12-19 DK DK01994315T patent/DK1343782T3/da active
- 2001-12-19 CZ CZ20031748A patent/CZ304059B6/cs not_active IP Right Cessation
- 2001-12-19 SI SI200130922T patent/SI1343782T1/sl unknown
- 2001-12-19 DE DE60138645T patent/DE60138645D1/de not_active Expired - Lifetime
- 2001-12-19 WO PCT/US2001/049367 patent/WO2002059110A1/en active IP Right Grant
- 2001-12-19 AU AU2002246723A patent/AU2002246723B2/en active Active
- 2001-12-19 US US10/451,305 patent/US7105530B2/en not_active Expired - Lifetime
- 2001-12-19 JP JP2002559412A patent/JP4253188B2/ja not_active Expired - Lifetime
- 2001-12-19 CA CA2432000A patent/CA2432000C/en not_active Expired - Lifetime
2003
- 2003-06-04 IL IL156306A patent/IL156306A/en active Protection Beyond IP Right Term
- 2003-06-09 ZA ZA2003/04482A patent/ZA200304482B/en unknown
- 2003-06-20 NO NO20032831A patent/NO325987B1/no active Protection Beyond IP Right Term
2004
- 2004-02-24 HK HK04101322.3A patent/HK1059926A1/xx not_active IP Right Cessation
2006
- 2006-05-15 US US11/383,229 patent/US7262203B2/en not_active Expired - Lifetime
2007
- 2007-07-30 US US11/830,024 patent/US7858626B2/en not_active Expired - Fee Related
- 2007-07-30 US US11/830,608 patent/US8114885B2/en not_active Expired - Fee Related
2009
- 2009-06-18 CY CY20091100644T patent/CY1109160T1/el unknown
- 2009-10-30 US US12/609,398 patent/US20100105712A1/en not_active Abandoned
2010
- 2010-07-21 LU LU91710C patent/LU91710I2/fr unknown
- 2010-07-29 CY CY2010014C patent/CY2010014I2/el unknown
- 2010-08-05 BE BE2010C030C patent/BE2010C030I2/fr unknown
- 2010-08-17 FR FR10C0037C patent/FR10C0037I2/fr active Active
- 2010-11-10 NO NO2010020C patent/NO2010020I1/no not_active IP Right Cessation
2011
- 2011-04-26 HK HK11104135.5A patent/HK1149930A1/xx not_active IP Right Cessation
2012
- 2012-07-10 US US13/545,029 patent/US20120277258A1/en not_active Abandoned
2017
- 2017-01-11 HU HUS1700003C patent/HUS1700003I1/hu unknown
2022
- 2022-01-06 NO NO2022001C patent/NO2022001I1/no unknown

Also Published As

Publication number	Publication date
KR20040011448A (ko)	2004-02-05
JP2004517925A (ja)	2004-06-17
PT2311825E (pt)	2016-01-22
US20070270427A1 (en)	2007-11-22
US20040242578A1 (en)	2004-12-02
CA2432000C (en)	2011-03-15
WO2002059110A1 (en)	2002-08-01
EP1343782B1 (de)	2009-05-06
CY2010014I1 (el)	2012-01-25
CZ20031748A3 (en)	2004-04-14
DE60138645D1 (de)	2009-06-18
PT1343782E (pt)	2009-06-29
JP4253188B2 (ja)	2009-04-08
US7262203B2 (en)	2007-08-28
EP2311825A1 (de)	2011-04-20
US8114885B2 (en)	2012-02-14
CA2432000A1 (en)	2002-08-01
NO20032831L (no)	2003-08-15
CZ304059B6 (cs)	2013-09-11
CN1549813A (zh)	2004-11-24
PL363243A1 (en)	2004-11-15
DE122010000038I1 (de)	2011-01-27
SI2311825T1 (sl)	2016-02-29
HU230574B1 (hu)	2023-11-28
HK1059926A1 (en)	2004-07-23
LU91710I9 (de)	2019-01-03
NZ526542A (en)	2005-01-28
CY1109160T1 (el)	2012-01-25
IL156306A0 (en)	2004-01-04
US20100105712A1 (en)	2010-04-29
NO2010020I1 (no)	2010-11-22
DK2311825T3 (en)	2016-01-18
US7105530B2 (en)	2006-09-12
FR10C0037I1 (fr)	2010-10-15
CN1307173C (zh)	2007-03-28
US20120277258A1 (en)	2012-11-01
BR0116452A (pt)	2003-09-30
SI1343782T1 (sl)	2009-10-31
CY2010014I2 (el)	2012-01-25
IL156306A (en)	2010-12-30
MXPA03005696A (es)	2003-10-06
ATE430742T1 (de)	2009-05-15
DK1343782T3 (da)	2009-08-24
NO2010020I2 (de)	2012-02-13
HUP0400691A3 (en)	2010-03-29
NO2022001I1 (no)	2022-01-06
US7858626B2 (en)	2010-12-28
US20070292513A1 (en)	2007-12-20
US20070015756A1 (en)	2007-01-18
HK1149930A1 (en)	2011-10-21
HUP0400691A2 (hu)	2004-07-28
ES2556946T3 (es)	2016-01-21
ES2324981T3 (es)	2009-08-21
BE2010C030I2 (de)	2021-06-17
PL214667B1 (pl)	2013-08-30
ZA200304482B (en)	2005-11-30
EP2311825B1 (de)	2015-10-07
AU2002246723B2 (en)	2005-07-14
NO20032831D0 (no)	2003-06-20
EP1343782A1 (de)	2003-09-17
FR10C0037I2 (fr)	2011-04-29
LU91710I2 (fr)	2010-09-21
HUS1700003I1 (hu)	2020-09-28
KR100847169B1 (ko)	2008-07-17

Legal Events

Date	Code	Title	Description
2010-11-22	SPCF	Filing of supplementary protection certificate	Free format text: PRODUCT NAME: VOTRIENT-PAZOPANIB; NAT. REG. NO/DATE: EU/1/10/628/001-004/N 20100628; FIRST REG. NO/DATE: EU/1/10/628/001-004 20100614 Spc suppl protection certif: 2010020 Filing date: 20101110
2012-02-13	SPCG	Granted supplementary protection certificate	Free format text: PRODUCT NAME: VOTRIENT-PAZOPANIB; NAT. REG. NO/DATE: EU/1/10/628/001-004/N 20100628; FIRST REG. NO/DATE: EU/1/10/628/001-004 20100614 Spc suppl protection certif: 2010020 Filing date: 20101110 Extension date: 20250614
2014-12-15	CHAD	Change of the owner's name or address (par. 44 patent law, par. patentforskriften)	Owner name: GLAXOSMITHKLINE LLC, US
2016-03-29	SPCK	Change in the validity period of an spc	Free format text: PROTECTION PERIOD CHANGED TO: 20250616 Spc suppl protection certif: 2010020
2022-01-10	MK1K	Patent expired
2022-01-17	SPCF	Filing of supplementary protection certificate	Free format text: PRODUCT NAME: PAZOPANIB; REG. NO/DATE: 20100628 Spc suppl protection certif: 2022001 Filing date: 20220106
2022-05-02	SPCT	Change of name or address of the representative of a supplementary protection certificate	Spc suppl protection certif: 2010020 Representative=s name: ZACCO NORWAY AS, POSTBOKS 488, 0213 OSLO, NORGE

Publication	Publication Date	Title
NO325987B1 (no)	2008-08-25	Pyrimidinaminer, anvendelse derav samt farmasoytisk preparat.
AU2003276125B2 (en)	2007-05-17	Chemical process
AU2002246723A1 (en)	2003-02-06	Pyrimidineamines as angiogenesis modulators
AU2005292152B2 (en)	2010-08-12	Aryl nitrogen-containing bicyclic compounds and their use as kinase inhibitors
MXPA04007637A (es)	2004-11-10	Compuestos de pirimidina.
KR102219160B1 (ko)	2021-02-23	N-(4-(아자인다졸-6-일)-페닐)-설폰아미드 및 약제로서의 그의 용도
EP1487824A1 (de)	2004-12-22	Diaminopyrimidine und deren verwendung als angiogenesehemmer
WO2004112714A2 (en)	2004-12-29	Chemical compounds