NO322214B1 - Forbindelser som er pyrrolotriazin-inhibitorer for kinaser, farmasoytiske preparater omfattende forbindelsene, samt anvendelser derav for fremstilling av er farmasoytisk preparat. - Google Patents

Forbindelser som er pyrrolotriazin-inhibitorer for kinaser, farmasoytiske preparater omfattende forbindelsene, samt anvendelser derav for fremstilling av er farmasoytisk preparat. Download PDF

Info

Publication number: NO322214B1
Authority: NO; Norway
Prior art keywords: triazine; carboxylic acid; amino; methyl ester; methylpyrrolo
Prior art date: 1999-05-21

Application number

NO20015650A

Other languages

English (en)

Norwegian (no)

Other versions

NO20015650L (no

NO20015650D0 (no

Inventor

John T Hunt

Rajeev S Bhide

Robert M Borzilleri

Ligang Qian

Original Assignee

Bristol Myers Squibb Co

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

1999-05-21

Filing date

2001-11-20

Publication date

2006-08-28

2001-11-20 Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co

2001-11-20 Publication of NO20015650L publication Critical patent/NO20015650L/no

2001-11-20 Publication of NO20015650D0 publication Critical patent/NO20015650D0/no

2006-08-28 Publication of NO322214B1 publication Critical patent/NO322214B1/no

Links

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239000003112 inhibitor Substances 0.000 title description 11
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239000008194 pharmaceutical composition Substances 0.000 title 2
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FLYWWNDDXORVRE-UHFFFAOYSA-N 5-[(5,7-dimethylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]-2-methylphenol Chemical compound C12=C(C)C=C(C)N2N=CN=C1NC1=CC=C(C)C(O)=C1 FLYWWNDDXORVRE-UHFFFAOYSA-N 0.000 claims description 2
KNVIJRHUKKOQEA-UHFFFAOYSA-N 5-[(5-ethylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]-2-methylphenol Chemical compound C12=C(CC)C=CN2N=CN=C1NC1=CC=C(C)C(O)=C1 KNVIJRHUKKOQEA-UHFFFAOYSA-N 0.000 claims description 2
OYWONCFUNIWAQD-UHFFFAOYSA-N 5-[[2-(dimethylamino)pyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]-2-methylphenol Chemical compound C12=CC=CN2N=C(N(C)C)N=C1NC1=CC=C(C)C(O)=C1 OYWONCFUNIWAQD-UHFFFAOYSA-N 0.000 claims description 2
SSEICAMCKGJKRN-UHFFFAOYSA-N 5-ethyl-4-[(6-methoxypyridin-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid Chemical compound C12=C(CC)C(C(O)=O)=CN2N=CN=C1NC1=CC=C(OC)N=C1 SSEICAMCKGJKRN-UHFFFAOYSA-N 0.000 claims description 2
VHPIKEMJVIXMSH-UHFFFAOYSA-N 5-methyl-4-(2-oxo-1,3-dihydroindol-3-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid Chemical compound O=C1NC2=CC=CC=C2C1C1=NC=NN2C=C(C(O)=O)C(C)=C12 VHPIKEMJVIXMSH-UHFFFAOYSA-N 0.000 claims description 2
SDPZKXVWIGGJLK-UHFFFAOYSA-N benzyl n-[5-ethyl-4-[(6-methoxypyridin-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-6-yl]carbamate Chemical compound C=1N2N=CN=C(NC=3C=NC(OC)=CC=3)C2=C(CC)C=1NC(=O)OCC1=CC=CC=C1 SDPZKXVWIGGJLK-UHFFFAOYSA-N 0.000 claims description 2
SBZWEENTHCBFJG-UHFFFAOYSA-N chembl400486 Chemical compound FC1=CC=C2C(C3=NC=NN4C=C(C(=C43)C)C(=O)OC)=C(O)NC2=C1 SBZWEENTHCBFJG-UHFFFAOYSA-N 0.000 claims description 2
ZLOWIHLTINOBGA-UHFFFAOYSA-N diethyl 4-(3-hydroxy-4-methylanilino)pyrrolo[2,1-f][1,2,4]triazine-5,6-dicarboxylate Chemical compound C12=C(C(=O)OCC)C(C(=O)OCC)=CN2N=CN=C1NC1=CC=C(C)C(O)=C1 ZLOWIHLTINOBGA-UHFFFAOYSA-N 0.000 claims description 2
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
ZTOVINQRRLDIIS-UHFFFAOYSA-N ethyl 4-[(6-methoxypyridin-3-yl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OCC)=CN2N=CN=C1NC1=CC=C(OC)N=C1 ZTOVINQRRLDIIS-UHFFFAOYSA-N 0.000 claims description 2
MPVVGXKXQOZABD-UHFFFAOYSA-N ethyl 5-ethyl-4-(2-oxo-1,3-dihydroindol-3-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound O=C1NC2=CC=CC=C2C1C1=NC=NN2C=C(C(=O)OCC)C(CC)=C21 MPVVGXKXQOZABD-UHFFFAOYSA-N 0.000 claims description 2
OKYDIKYNMQSXSY-UHFFFAOYSA-N ethyl 5-ethyl-4-[3-(methanesulfonamido)-4-methylanilino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(CC)C(C(=O)OCC)=CN2N=CN=C1NC1=CC=C(C)C(NS(C)(=O)=O)=C1 OKYDIKYNMQSXSY-UHFFFAOYSA-N 0.000 claims description 2
229940022353 herceptin Drugs 0.000 claims 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 claims description 2
229960004768 irinotecan Drugs 0.000 claims description 2
GZOLPVDOLYQBMB-UHFFFAOYSA-N methyl 4-(1h-indol-6-ylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C1=C2C=CNC2=CC(NC2=NC=NN3C=C(C(=C32)C)C(=O)OC)=C1 GZOLPVDOLYQBMB-UHFFFAOYSA-N 0.000 claims description 2
GKAZEUGTXYNBFY-UHFFFAOYSA-N methyl 4-(2,3-dihydro-1,4-benzodioxin-6-ylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound O1CCOC2=CC(NC3=NC=NN4C=C(C(=C43)C)C(=O)OC)=CC=C21 GKAZEUGTXYNBFY-UHFFFAOYSA-N 0.000 claims description 2
YFGKHNXPJPMCFJ-UHFFFAOYSA-N methyl 4-(3-hydroxy-4-methoxyanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(OC)C(O)=C1 YFGKHNXPJPMCFJ-UHFFFAOYSA-N 0.000 claims description 2
HDUYYHXMLYTCAI-UHFFFAOYSA-N methyl 4-(3-hydroxyanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=CC(O)=C1 HDUYYHXMLYTCAI-UHFFFAOYSA-N 0.000 claims description 2
HGLFWYTYWBQLDW-UHFFFAOYSA-N methyl 4-(3-hydroxyphenoxy)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1OC1=CC=CC(O)=C1 HGLFWYTYWBQLDW-UHFFFAOYSA-N 0.000 claims description 2
MNXPSLVOIQHJAN-UHFFFAOYSA-N methyl 4-(4-chloro-3-nitroanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(Cl)C([N+]([O-])=O)=C1 MNXPSLVOIQHJAN-UHFFFAOYSA-N 0.000 claims description 2
XLAJOHUNILNDLC-UHFFFAOYSA-N methyl 4-(5-carbamoyl-2-oxo-1,3-dihydroindol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound O=C1NC2=CC=C(C(N)=O)C=C2C1C1=NC=NN2C=C(C(=O)OC)C(C)=C21 XLAJOHUNILNDLC-UHFFFAOYSA-N 0.000 claims description 2
HNFPSZBXRLSFSU-UHFFFAOYSA-N methyl 4-[(1,3-dioxoisoindol-5-yl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C1=C2C(=O)NC(=O)C2=CC(NC2=NC=NN3C=C(C(=C32)C)C(=O)OC)=C1 HNFPSZBXRLSFSU-UHFFFAOYSA-N 0.000 claims description 2
QBXSUGIMUCOYBG-UHFFFAOYSA-N methyl 4-[(1-benzylindazol-5-yl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 QBXSUGIMUCOYBG-UHFFFAOYSA-N 0.000 claims description 2
DVQZXKDRIWJVMP-UHFFFAOYSA-N methyl 4-[(6-methoxypyridin-3-yl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(OC)N=C1 DVQZXKDRIWJVMP-UHFFFAOYSA-N 0.000 claims description 2
GYHKNUWTEFVSCN-UHFFFAOYSA-N methyl 4-[3-(hydrazinecarbonyl)anilino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=CC(C(=O)NN)=C1 GYHKNUWTEFVSCN-UHFFFAOYSA-N 0.000 claims description 2
FBQMXMWCIZVMNC-UHFFFAOYSA-N methyl 4-[3-(hydroxymethyl)anilino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=CC(CO)=C1 FBQMXMWCIZVMNC-UHFFFAOYSA-N 0.000 claims description 2
QQQPACPTNIDJCA-UHFFFAOYSA-N methyl 4-[5-(2-hydroxyethylsulfamoyl)-2-oxo-1,3-dihydroindol-3-yl]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound O=C1NC2=CC=C(S(=O)(=O)NCCO)C=C2C1C1=NC=NN2C=C(C(=O)OC)C(C)=C21 QQQPACPTNIDJCA-UHFFFAOYSA-N 0.000 claims description 2
RQLQWLJKCZHOIM-UHFFFAOYSA-N methyl 5-ethyl-4-[(6-methoxypyridin-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(CC)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(OC)N=C1 RQLQWLJKCZHOIM-UHFFFAOYSA-N 0.000 claims description 2
QYEALBQJKRHZQW-UHFFFAOYSA-N methyl 5-methyl-4-(1h-pyrazol-5-ylamino)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC=1C=CNN=1 QYEALBQJKRHZQW-UHFFFAOYSA-N 0.000 claims description 2
CJPKZAUMMYLARG-UHFFFAOYSA-N methyl 5-methyl-4-(3-oxo-1h-indazol-2-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound N1C2=CC=CC=C2C(=O)N1C1=NC=NN2C=C(C(=O)OC)C(C)=C21 CJPKZAUMMYLARG-UHFFFAOYSA-N 0.000 claims description 2
KTNDTJVXEQRHRU-UHFFFAOYSA-N methyl 5-methyl-4-(3-oxo-2,4-dihydroquinoxalin-1-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C1C(=O)NC2=CC=CC=C2N1C1=NC=NN2C=C(C(=O)OC)C(C)=C21 KTNDTJVXEQRHRU-UHFFFAOYSA-N 0.000 claims description 2
WQQASJBTDWIWDV-UHFFFAOYSA-N methyl 5-methyl-4-(3-oxo-2h-indazol-1-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound N1C(=O)C2=CC=CC=C2N1C1=NC=NN2C=C(C(=O)OC)C(C)=C21 WQQASJBTDWIWDV-UHFFFAOYSA-N 0.000 claims description 2
RRFQIXSTCQXRJH-UHFFFAOYSA-N methyl 5-methyl-4-(4-methyl-3-nitroanilino)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(C)C([N+]([O-])=O)=C1 RRFQIXSTCQXRJH-UHFFFAOYSA-N 0.000 claims description 2
CMHKTCZJLHLZPT-UHFFFAOYSA-N methyl 5-methyl-4-(4-methyl-3-sulfamoylanilino)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CMHKTCZJLHLZPT-UHFFFAOYSA-N 0.000 claims description 2
JOHFSMPXICYLLT-UHFFFAOYSA-N methyl 5-methyl-4-(4-phenoxyanilino)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC(C=C1)=CC=C1OC1=CC=CC=C1 JOHFSMPXICYLLT-UHFFFAOYSA-N 0.000 claims description 2
ZTHCOUWUGAEMFY-UHFFFAOYSA-N methyl 5-methyl-4-(6-methylsulfonyl-2-oxo-1,3-dihydroindol-3-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound O=C1NC2=CC(S(C)(=O)=O)=CC=C2C1C1=NC=NN2C=C(C(=O)OC)C(C)=C21 ZTHCOUWUGAEMFY-UHFFFAOYSA-N 0.000 claims description 2
LRFKLXQCKKTUKG-UHFFFAOYSA-N methyl 5-methyl-4-(quinolin-5-ylamino)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C1=CC=C2C(NC3=NC=NN4C=C(C(=C43)C)C(=O)OC)=CC=CC2=N1 LRFKLXQCKKTUKG-UHFFFAOYSA-N 0.000 claims description 2
UQWPABVGTSYMKX-UHFFFAOYSA-N methyl 5-methyl-4-[(5-methylpyridin-2-yl)amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(C)C=N1 UQWPABVGTSYMKX-UHFFFAOYSA-N 0.000 claims description 2
JVEDGNVJCQGYSS-UHFFFAOYSA-N n-(4-chloro-2-fluorophenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine Chemical compound FC1=CC(Cl)=CC=C1NC1=NC=NN2C1=CC=C2 JVEDGNVJCQGYSS-UHFFFAOYSA-N 0.000 claims description 2
OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical class NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 claims description 2
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
RLNCTIUJEJXMBZ-UHFFFAOYSA-N pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide Chemical compound C1=NC=NN2C=C(C(=O)N)C=C21 RLNCTIUJEJXMBZ-UHFFFAOYSA-N 0.000 claims description 2
230000001603 reducing effect Effects 0.000 claims description 2
NPIISCWCOBHJGF-UHFFFAOYSA-N 1-[6-(pyrrolo[2,1-f][1,2,4]triazin-4-ylamino)-2,3-dihydroindol-1-yl]ethanone Chemical compound C1=NN2C=CC=C2C(NC2=CC=C3CCN(C3=C2)C(=O)C)=N1 NPIISCWCOBHJGF-UHFFFAOYSA-N 0.000 claims 1
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
QVHFAUADDZADAN-UHFFFAOYSA-N 2-methyl-5-(pyrrolo[2,1-f][1,2,4]triazin-4-ylamino)phenol Chemical compound C1=C(O)C(C)=CC=C1NC1=NC=NN2C1=CC=C2 QVHFAUADDZADAN-UHFFFAOYSA-N 0.000 claims 1
ATRMGRIXDIZXRO-UHFFFAOYSA-N 2-methyl-5-[(5-methylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]phenol Chemical compound C12=C(C)C=CN2N=CN=C1NC1=CC=C(C)C(O)=C1 ATRMGRIXDIZXRO-UHFFFAOYSA-N 0.000 claims 1
BNJHLXRPLVJJDL-UHFFFAOYSA-N 2-methyl-5-[(6-methylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]phenol Chemical compound N=1C=NN2C=C(C)C=C2C=1NC1=CC=C(C)C(O)=C1 BNJHLXRPLVJJDL-UHFFFAOYSA-N 0.000 claims 1
QFAYCQKPUDKQJB-UHFFFAOYSA-N 2-methyl-5-[(7-methylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]phenol Chemical compound N=1C=NN2C(C)=CC=C2C=1NC1=CC=C(C)C(O)=C1 QFAYCQKPUDKQJB-UHFFFAOYSA-N 0.000 claims 1
125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims 1
MZDDOGMKTHYLKJ-UHFFFAOYSA-N 4-(3-hydroxy-4-methylanilino)-5-methyl-n-(2-pyrrolidin-1-ylethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide Chemical compound C12=C(C)C(C(=O)NCCN3CCCC3)=CN2N=CN=C1NC1=CC=C(C)C(O)=C1 MZDDOGMKTHYLKJ-UHFFFAOYSA-N 0.000 claims 1
WQLIOGMNMDBAAX-UHFFFAOYSA-N 5-[(6-ethyl-5,7-dimethylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]-2-methylphenol Chemical compound N=1C=NN2C(C)=C(CC)C(C)=C2C=1NC1=CC=C(C)C(O)=C1 WQLIOGMNMDBAAX-UHFFFAOYSA-N 0.000 claims 1
FTGMAZNZVBHTAD-UHFFFAOYSA-N 5-[[6-(hydroxymethyl)-5-methylpyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]-2-methylphenol Chemical compound C12=C(C)C(CO)=CN2N=CN=C1NC1=CC=C(C)C(O)=C1 FTGMAZNZVBHTAD-UHFFFAOYSA-N 0.000 claims 1
QEQRJVUCJACZTO-UHFFFAOYSA-N 5-methyl-n-(3-morpholin-4-ylpropyl)-4-(2-oxo-1,3-dihydroindol-3-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide Chemical compound C=1N2N=CN=C(C3C4=CC=CC=C4NC3=O)C2=C(C)C=1C(=O)NCCCN1CCOCC1 QEQRJVUCJACZTO-UHFFFAOYSA-N 0.000 claims 1
NEUKZNKEOJUFJS-UHFFFAOYSA-N 7-bromo-n-(4-chlorophenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine Chemical compound C1=CC(Cl)=CC=C1NC1=NC=NN2C1=CC=C2Br NEUKZNKEOJUFJS-UHFFFAOYSA-N 0.000 claims 1
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims 1
DVQHYTBCTGYNNN-UHFFFAOYSA-N azane;cyclobutane-1,1-dicarboxylic acid;platinum Chemical compound N.N.[Pt].OC(=O)C1(C(O)=O)CCC1 DVQHYTBCTGYNNN-UHFFFAOYSA-N 0.000 claims 1
UUQGIFBMQJPEQA-UHFFFAOYSA-N ethyl 4-(4-bromo-2-fluoroanilino)-5-methoxypyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(OC)C(C(=O)OCC)=CN2N=CN=C1NC1=CC=C(Br)C=C1F UUQGIFBMQJPEQA-UHFFFAOYSA-N 0.000 claims 1
RHBOWHNVBCWQNE-UHFFFAOYSA-N ethyl 4-[(6-chloropyridin-3-yl)amino]-5-ethylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(CC)C(C(=O)OCC)=CN2N=CN=C1NC1=CC=C(Cl)N=C1 RHBOWHNVBCWQNE-UHFFFAOYSA-N 0.000 claims 1
CRIXUQMXXYMARY-UHFFFAOYSA-N methyl 4-(2,3-dihydro-1h-indol-6-ylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C1=C2CCNC2=CC(NC2=NC=NN3C=C(C(=C32)C)C(=O)OC)=C1 CRIXUQMXXYMARY-UHFFFAOYSA-N 0.000 claims 1
UEMMUOLAXAGUOE-UHFFFAOYSA-N methyl 4-(3,4-dimethoxyanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(OC)C(OC)=C1 UEMMUOLAXAGUOE-UHFFFAOYSA-N 0.000 claims 1
QNYCTGJEBPXCTG-UHFFFAOYSA-N methyl 4-(3-hydroxy-2-methylanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=CC(O)=C1C QNYCTGJEBPXCTG-UHFFFAOYSA-N 0.000 claims 1
UUJOHQIBEVTNOG-UHFFFAOYSA-N methyl 4-(3-methoxy-4-methylanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(C)C(OC)=C1 UUJOHQIBEVTNOG-UHFFFAOYSA-N 0.000 claims 1
MNNKPBFQXFETNB-UHFFFAOYSA-N methyl 4-(4-bromo-3-methylanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(Br)C(C)=C1 MNNKPBFQXFETNB-UHFFFAOYSA-N 0.000 claims 1
GVERDVRZRGMLFU-UHFFFAOYSA-N methyl 4-(4-methoxyanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(OC)C=C1 GVERDVRZRGMLFU-UHFFFAOYSA-N 0.000 claims 1
GCEQGTGMPGWITJ-UHFFFAOYSA-N methyl 4-[(1,4-dioxo-2,3-dihydrophthalazin-6-yl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound O=C1NNC(=O)C=2C1=CC(NC1=NC=NN3C=C(C(=C31)C)C(=O)OC)=CC=2 GCEQGTGMPGWITJ-UHFFFAOYSA-N 0.000 claims 1
MXCCSODVRVBQDW-UHFFFAOYSA-N methyl 4-[(6-acetamidopyridin-3-yl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(NC(C)=O)N=C1 MXCCSODVRVBQDW-UHFFFAOYSA-N 0.000 claims 1
IWFGSLJPHSRHBZ-UHFFFAOYSA-N methyl 4-[5-(hydroxymethyl)-2-methylanilino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC(CO)=CC=C1C IWFGSLJPHSRHBZ-UHFFFAOYSA-N 0.000 claims 1
ACBLGNYVHXMIRT-UHFFFAOYSA-N methyl 4-[5-(methanesulfonamido)-2-methylanilino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC(NS(C)(=O)=O)=CC=C1C ACBLGNYVHXMIRT-UHFFFAOYSA-N 0.000 claims 1
XETYQQCOCNFGNU-UHFFFAOYSA-N methyl 5-methyl-4-(2-oxo-5-sulfamoyl-1,3-dihydroindol-3-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound O=C1NC2=CC=C(S(N)(=O)=O)C=C2C1C1=NC=NN2C=C(C(=O)OC)C(C)=C21 XETYQQCOCNFGNU-UHFFFAOYSA-N 0.000 claims 1
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BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
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IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
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LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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208000010570 urinary bladder carcinoma Diseases 0.000 description 1
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Classifications

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NO20015650A 1999-05-21 2001-11-20 Forbindelser som er pyrrolotriazin-inhibitorer for kinaser, farmasoytiske preparater omfattende forbindelsene, samt anvendelser derav for fremstilling av er farmasoytisk preparat. NO322214B1 (no)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US13526599P	1999-05-21	1999-05-21
US19372700P	2000-03-31	2000-03-31
PCT/US2000/013420 WO2000071129A1 (en)	1999-05-21	2000-05-16	Pyrrolotriazine inhibitors of kinases

Publications (3)

Publication Number	Publication Date
NO20015650L NO20015650L (no)	2001-11-20
NO20015650D0 NO20015650D0 (no)	2001-11-20
NO322214B1 true NO322214B1 (no)	2006-08-28

Family

ID=26833147

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20015650A NO322214B1 (no)	1999-05-21	2001-11-20	Forbindelser som er pyrrolotriazin-inhibitorer for kinaser, farmasoytiske preparater omfattende forbindelsene, samt anvendelser derav for fremstilling av er farmasoytisk preparat.

Country Status (28)

Country	Link
EP (1)	EP1183033B1 (es)
JP (2)	JP4649046B2 (es)
KR (1)	KR100666514B1 (es)
CN (1)	CN1351498B (es)
AR (1)	AR043087A1 (es)
AT (1)	ATE318603T1 (es)
AU (1)	AU770377B2 (es)
BR (1)	BR0010482A (es)
CA (1)	CA2373990C (es)
CZ (1)	CZ303660B6 (es)
DE (2)	DE60042620D1 (es)
DK (1)	DK1183033T3 (es)
EG (1)	EG24027A (es)
ES (2)	ES2328269T3 (es)
HK (1)	HK1041599B (es)
HU (1)	HUP0301005A3 (es)
IL (2)	IL144977A0 (es)
MX (1)	MXPA01011832A (es)
MY (1)	MY128370A (es)
NO (1)	NO322214B1 (es)
NZ (1)	NZ516292A (es)
PE (1)	PE20010126A1 (es)
PL (1)	PL204437B1 (es)
RU (1)	RU2331640C2 (es)
TR (1)	TR200103352T2 (es)
TW (1)	TWI238163B (es)
UY (1)	UY26150A1 (es)
WO (1)	WO2000071129A1 (es)

Families Citing this family (185)

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Publication number	Priority date	Publication date	Assignee	Title
EP1183033B1 (en) *	1999-05-21	2006-03-01	Bristol-Myers Squibb Company	Pyrrolotriazine inhibitors of kinases
JP4623483B2 (ja) *	1999-08-23	2011-02-02	塩野義製薬株式会社	ｓＰＬＡ２阻害作用を有するピロロトリアジン誘導体
JP2004505965A (ja) *	2000-08-09	2004-02-26	アストラゼネカ　アクチボラグ	化合物
PT1313734E (pt)	2000-09-01	2010-02-09	Novartis Vaccines & Diagnostic	Derivados aza heterocíclicos e sua utilização terapêutica
ATE309996T1 (de)	2000-09-11	2005-12-15	Chiron Corp	Chinolinonderivate als tyrosin-kinase inhibitoren
US20030028018A1 (en) *	2000-09-11	2003-02-06	Chiron Coporation	Quinolinone derivatives
US6867300B2 (en)	2000-11-17	2005-03-15	Bristol-Myers Squibb Company	Methods for the preparation of pyrrolotriazine compounds useful as kinase inhibitors
GEP20063915B (en) *	2000-11-17	2006-09-11	Bristol Myers Squibb Co	PYRROLOTRIAZINE COMPOUNDS USEFUL AS KINASE INHIBITORS AND USE THEREOF FOR TREATING p38 KINASE-ASSOCIATED CONDITIONS
US6670357B2 (en) *	2000-11-17	2003-12-30	Bristol-Myers Squibb Company	Methods of treating p38 kinase-associated conditions and pyrrolotriazine compounds useful as kinase inhibitors
US6699890B2 (en)	2000-12-22	2004-03-02	Memory Pharmaceuticals Corp.	Phosphodiesterase 4 inhibitors
US7153871B2 (en)	2001-01-22	2006-12-26	Memory Pharmaceuticals Corporation	Phosphodiesterase 4 inhibitors, including aminoindazole and aminobenzofuran analogs
HUP0302793A3 (en) *	2001-01-22	2006-01-30	Memory Pharmaceuticals Corp Mo	N-substituted aniline derivatives useful as phosphodiesterase 4 inhibitors, pharmaceutical compositions containing them and process for their preparations
US7205320B2 (en)	2001-01-22	2007-04-17	Memory Pharmaceuticals Corp.	Phosphodiesterase 4 inhibitors
CA2440553C (en) *	2001-03-13	2010-06-08	Paul J. Gilligan	4-(2-butylamino)-2,7-dimethyl-8-(2-methyl-6-methoxypyrid-3-yl)pyrazolo-[1,5-a]-1,3,5-triazine, its enantiomers and pharmaceutically acceptable salts as corticotropin releasing factor receptor ligands
TW200300350A (en) *	2001-11-14	2003-06-01	Bristol Myers Squibb Co	C-5 modified indazolylpyrrolotriazines
SE0200979D0 (sv) *	2002-03-28	2002-03-28	Astrazeneca Ab	New compounds
US6900208B2 (en)	2002-03-28	2005-05-31	Bristol Myers Squibb Company	Pyrrolopyridazine compounds and methods of use thereof for the treatment of proliferative disorders
SE0302546D0 (sv)	2003-09-24	2003-09-24	Astrazeneca Ab	New compounds
FR2838123B1 (fr) *	2002-04-04	2005-06-10	Sanofi Synthelabo	Nouveaux derives d'indolozine-1,2,3 substituee, inhibiteurs selectifs du b-fgf
US7388009B2 (en)	2002-04-23	2008-06-17	Bristol-Myers Squibb Company	Heteroaryl-substituted pyrrolo-triazine compounds useful as kinase inhibitors
WO2003090912A1 (en)	2002-04-23	2003-11-06	Bristol-Myers Squibb Company	Pyrrolo-triazine aniline compounds useful as kinase inhibitors
ATE418546T1 (de)	2002-04-23	2009-01-15	Bristol Myers Squibb Co	Als kinase inhibitoren geeignete arylketonpyrrolotriazin-verbindungen
TW200400034A (en)	2002-05-20	2004-01-01	Bristol Myers Squibb Co	Pyrazolo-pyrimidine aniline compounds useful as kinase inhibitors
AU2003236557B2 (en) *	2002-06-27	2009-10-01	Verva Pharmaceuticals Pty Ltd	Differentiation modulating agents and uses therefor
TWI329112B (en) *	2002-07-19	2010-08-21	Bristol Myers Squibb Co	Novel inhibitors of kinases
HRP20050082A2 (en)	2002-07-19	2005-06-30	Memory Pharmaceuticals Corporation	6-amino-1h-indazole and 4-aminobenzofuran compounds as phosphodiesterase 4 inhibitors
US6933386B2 (en)	2002-07-19	2005-08-23	Bristol Myers Squibb Company	Process for preparing certain pyrrolotriazine compounds
KR100869417B1 (ko) *	2002-07-19	2008-11-21	브리스톨-마이어스 스큅 컴퍼니	신규한 키나제 억제제
RU2368604C2 (ru)	2002-07-19	2009-09-27	Мемори Фармасьютиклз Корпорейшн	Ингибиторы фосфодиэстеразы 4, включающие n-замещенные аналоги анилина и дифениламина
EP1388541A1 (en)	2002-08-09	2004-02-11	Centre National De La Recherche Scientifique (Cnrs)	Pyrrolopyrazines as kinase inhibitors
EP1539754A4 (en)	2002-08-23	2009-02-25	Novartis Vaccines & Diagnostic	BENZIMIDAZOCHINOLINONE AND ITS USE
US7087625B2 (en)	2002-11-19	2006-08-08	Memory Pharmaceuticals Corporation	Phosphodiesterase 4 inhibitors
TW200420565A (en) *	2002-12-13	2004-10-16	Bristol Myers Squibb Co	C-6 modified indazolylpyrrolotriazines
PL378121A1 (pl)	2003-02-05	2006-03-06	Bristol-Myers Squibb Company	Sposób wytwarzania pirolotriazynowych inhibitorów kinazy
US7102001B2 (en)	2003-12-12	2006-09-05	Bristol-Myers Squibb Company	Process for preparing pyrrolotriazine
MY145634A (en) *	2003-12-29	2012-03-15	Bristol Myers Squibb Co	Pyrrolotriazine compounds as kinase inhibitors
US7064203B2 (en)	2003-12-29	2006-06-20	Bristol Myers Squibb Company	Di-substituted pyrrolotriazine compounds
CN1960993A (zh)	2004-04-02	2007-05-09	Osi制药公司	6,6－双环取代的杂双环蛋白激酶抑制剂
US7459562B2 (en)	2004-04-23	2008-12-02	Bristol-Myers Squibb Company	Monocyclic heterocycles as kinase inhibitors
TW200538453A (en)	2004-04-26	2005-12-01	Bristol Myers Squibb Co	Bicyclic heterocycles as kinase inhibitors
UY28931A1 (es) *	2004-06-03	2005-12-30	Bayer Pharmaceuticals Corp	Derivados de pirrolotriazina utiles para tratar trastornos hiper-proliferativos y enfermedades asociadas con angiogenesis
US7102002B2 (en)	2004-06-16	2006-09-05	Bristol-Myers Squibb Company	Pyrrolotriazine kinase inhibitors
US20050288290A1 (en)	2004-06-28	2005-12-29	Borzilleri Robert M	Fused heterocyclic kinase inhibitors
US7432373B2 (en)	2004-06-28	2008-10-07	Bristol-Meyers Squibb Company	Processes and intermediates useful for preparing fused heterocyclic kinase inhibitors
US7439246B2 (en)	2004-06-28	2008-10-21	Bristol-Myers Squibb Company	Fused heterocyclic kinase inhibitors
TW200600513A (en)	2004-06-30	2006-01-01	Bristol Myers Squibb Co	A method for preparing pyrrolotriazine compounds
US7102003B2 (en)	2004-07-01	2006-09-05	Bristol-Myers Squibb Company	Pyrrolotriazine compounds
AR053090A1 (es) *	2004-07-20	2007-04-25	Osi Pharm Inc	Imidazotriazinas como inhibidores de proteina quinasas y su uso para la preparacion de medicamentos
US7504521B2 (en)	2004-08-05	2009-03-17	Bristol-Myers Squibb Co.	Methods for the preparation of pyrrolotriazine compounds
PE20060421A1 (es)	2004-08-12	2006-06-01	Bristol Myers Squibb Co	Procedimiento para preparar un compuesto de pirrolotriazina anilina como inhibidores de cinasa
US7713973B2 (en) *	2004-10-15	2010-05-11	Takeda Pharmaceutical Company Limited	Kinase inhibitors
US7151176B2 (en) *	2004-10-21	2006-12-19	Bristol-Myers Squibb Company	Pyrrolotriazine compounds
US7759337B2 (en)	2005-03-03	2010-07-20	Amgen Inc.	Phthalazine compounds and methods of use
US7534882B2 (en)	2005-04-06	2009-05-19	Bristol-Myers Squibb Company	Method for preparing pyrrolotriazine compounds via in situ amination of pyrroles
MY158766A (en)	2005-04-11	2016-11-15	Xenon Pharmaceuticals Inc	Spiro-oxindole compounds and their uses as therapeutic agents
AR053710A1 (es)	2005-04-11	2007-05-16	Xenon Pharmaceuticals Inc	Compuestos espiroheterociclicos y sus usos como agentes terapeuticos
KR100695700B1 (ko) *	2005-04-20	2007-03-15	김세중	조립식 경량벽체 패널과 그 조립구조
KR100672087B1 (ko) *	2005-04-25	2007-01-19	재단법인 포항산업과학연구원	폐단형 스터드부재 및 이를 이용한 단열 벽체 시스템
PL1888556T3 (pl)	2005-05-17	2012-03-30	Novartis Ag	Metody syntetyzowania związków heterocyklicznych
US7576082B2 (en) *	2005-06-24	2009-08-18	Hoffman-La Roche Inc.	Oxindole derivatives
US7402582B2 (en)	2005-07-01	2008-07-22	Bristol-Myers Squibb Company	Pyrrolotriazine compounds useful as kinase inhibitors and methods of treating kinase-associated conditions therewith
US7405213B2 (en)	2005-07-01	2008-07-29	Bristol-Myers Squibb Company	Pyrrolotriazine compounds useful as kinase inhibitors and methods of treating kinase-associated conditions therewith
JP4994379B2 (ja)	2005-09-01	2012-08-08	ブリストル−マイヤーズスクイブカンパニー	血管内皮成長因子受容体−２モジュレーターに対する感受性を決定するためのバイオマーカーおよび方法
US7880004B2 (en)	2005-09-15	2011-02-01	Bristol-Myers Squibb Company	Met kinase inhibitors
CA2623125A1 (en)	2005-09-20	2007-03-29	Osi Pharmaceuticals, Inc.	Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors
US7547782B2 (en)	2005-09-30	2009-06-16	Bristol-Myers Squibb Company	Met kinase inhibitors
ES2401099T3 (es) *	2005-11-02	2013-04-16	Bayer Intellectual Property Gmbh	Pirrolo[2,1-F] [1,2,4]-triazin-4-ilaminas como inhibidores de la quinasa IGF-1R para el tratamiento del cáncer y de otras enfermedades hiperproliferativas
US7514435B2 (en)	2005-11-18	2009-04-07	Bristol-Myers Squibb Company	Pyrrolotriazine kinase inhibitors
US7348325B2 (en)	2005-11-30	2008-03-25	Bristol-Myers Squibb Company	Pyrrolotriazine kinase inhibitors
EP1957485B1 (en)	2005-12-02	2013-02-13	Bayer HealthCare, LLC	Substituted 4-amino-pyrrolotriazine derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis
PE20070855A1 (es)	2005-12-02	2007-10-14	Bayer Pharmaceuticals Corp	Derivados de 4-amino-pirrolotriazina sustituida como inhibidores de quinasas
AR057960A1 (es)	2005-12-02	2007-12-26	Osi Pharm Inc	Inhibidores de proteina quinasa biciclicos
US8063208B2 (en)	2006-02-16	2011-11-22	Bristol-Myers Squibb Company	Crystalline forms of (3R,4R)-4-amino-1-[[4-[(3-methoxyphenyl)amino]pyrrolo[2,1-f][1,2,4]triazin-5-yl]methyl]piperidin-3-ol
ATE537450T1 (de)	2006-06-30	2011-12-15	Schering Corp	Igfbp2-biomarker
AU2007269163B2 (en)	2006-07-07	2011-07-28	Bristol-Myers Squibb Company	Pyrrolotriazine kinase inhibitors
EP2049542B1 (en)	2006-08-09	2012-09-19	Bristol-Myers Squibb Company	Pyrrolotriazine kinase inhibitors
US7531539B2 (en)	2006-08-09	2009-05-12	Bristol-Myers Squibb Company	Pyrrolotriazine kinase inhibitors
JP5460324B2 (ja)	2006-10-12	2014-04-02	ゼノン・ファーマシューティカルズ・インコーポレイテッド	治療剤としてのスピロ−オキシインドール化合物の使用
EP2081936B1 (en)	2006-11-03	2014-04-02	Bristol-Myers Squibb Company	Pyrrolotriazine kinase inhibitors
US8268998B2 (en)	2006-11-03	2012-09-18	Bristol-Myers Squibb Company	Pyrrolotriazine kinase inhibitors
CN101627027B (zh) *	2007-01-05	2013-06-19	百时美施贵宝公司	氨基吡唑激酶抑制剂
KR20090128474A (ko)	2007-04-13	2009-12-15	브리스톨-마이어스 스큅 컴퍼니	혈관 내피 성장인자 수용체-2 조절제에 대한 감수성을 판정하기 위한 방법 및 바이오마커
EP2134716A1 (en)	2007-04-18	2009-12-23	Bristol-Myers Squibb Company	Pyrrolotriazine kinase inhibitors
MX2010003269A (es)	2007-09-25	2010-08-02	Bayer Healthcare Llc	Derivados de pirrolotriazina utiles para tratar cancer a traves de la inhibicion de la aurora quinasa.
AU2008308691B2 (en)	2007-10-01	2013-11-07	Isis Pharmaceuticals, Inc.	Antisense modulation of fibroblast growth factor receptor 4 expression
MX2010004327A (es)	2007-10-22	2010-05-13	Schering Corp	Anticuerpos anti-vegf completamente humanos y metodos de uso.
MX2010007523A (es)	2008-01-11	2010-08-18	Natco Pharma Ltd	Nuevos derivados de pirazolo[3,4-d]pirimidina como farmacos anticancer.
MX2010010151A (es)	2008-03-20	2010-10-25	Amgen Inc	Moduladores de cinasa aurora y metodo de uso.
WO2010019473A1 (en)	2008-08-14	2010-02-18	Amgen Inc.	Aurora kinase modulators and methods of use
WO2010042684A1 (en) *	2008-10-08	2010-04-15	Bristol-Myers Squibb Company	Pyrrolotriazine kinase inhibitors
US8497269B2 (en)	2008-10-10	2013-07-30	Amgen Inc.	Phthalazine compounds as p38 map kinase modulators and methods of use thereof
WO2010042646A1 (en)	2008-10-10	2010-04-15	Amgen Inc.	Aza- and diaza-phthalazine compounds as p38 map kinase modulators and methods of use thereof
WO2010045197A1 (en)	2008-10-17	2010-04-22	Xenon Pharmaceuticals, Inc.	Spiro-oxindole compounds and their use as therapeutic agents
CN105218565A (zh)	2008-10-17	2016-01-06	泽农医药公司	螺羟吲哚化合物及其作为治疗剂的用途
CA2742986C (en)	2008-11-07	2015-03-31	Triact Therapeutics, Inc.	Use of catecholic butane derivatives in cancer therapy
WO2010071885A1 (en)	2008-12-19	2010-06-24	Cephalon, Inc.	Pyrrolotriazines as alk and jak2 inhibitors
US8273754B2 (en)	2008-12-30	2012-09-25	Arqule, Inc.	Substituted 1H-pyrazolo[3,4-D]pyrimidine-6-amine compounds
WO2010099139A2 (en)	2009-02-25	2010-09-02	Osi Pharmaceuticals, Inc.	Combination anti-cancer therapy
EP2400990A2 (en)	2009-02-26	2012-01-04	OSI Pharmaceuticals, LLC	In situ methods for monitoring the emt status of tumor cells in vivo
US8465912B2 (en)	2009-02-27	2013-06-18	OSI Pharmaceuticals, LLC	Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation
WO2010099138A2 (en)	2009-02-27	2010-09-02	Osi Pharmaceuticals, Inc.	Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation
US8642834B2 (en)	2009-02-27	2014-02-04	OSI Pharmaceuticals, LLC	Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation
EP2424368B1 (en)	2009-04-29	2014-12-31	Locus Pharmaceuticals, Inc.	Pyrrolotriazine compounds
AR077252A1 (es)	2009-06-29	2011-08-10	Xenon Pharmaceuticals Inc	Enantiomeros de compuestos de espirooxindol y sus usos como agentes terapeuticos
CN102595900B (zh)	2009-08-10	2015-07-15	萨穆梅德有限公司	Wnt信号传导途径的吲唑抑制剂及其治疗用途
US8445696B2 (en)	2009-10-14	2013-05-21	Xenon Pharmaceuticals Inc.	Synthetic methods for spiro-oxindole compounds
US8088815B2 (en)	2009-12-02	2012-01-03	Hoffman-La Roche Inc.	Spiroindolinone pyrrolidines
EP2515655B1 (en)	2009-12-21	2015-08-05	Samumed, LLC	1h-pyrazolo[3,4-beta]pyridines and therapeutic uses thereof
US8288431B2 (en)	2010-02-17	2012-10-16	Hoffmann-La Roche Inc.	Substituted spiroindolinones
CA2788440A1 (en)	2010-02-26	2011-09-01	Xenon Pharmaceuticals Inc.	Pharmaceutical compositions of spiro-oxindole compound for topical administration and their use as therapeutic agents
US20110275644A1 (en)	2010-03-03	2011-11-10	Buck Elizabeth A	Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors
EP2542893A2 (en)	2010-03-03	2013-01-09	OSI Pharmaceuticals, LLC	Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors
US20130005733A1 (en)	2010-03-09	2013-01-03	OSI Pharmaceuticals, LLC	Combination anti-cancer therapy
US8217044B2 (en)	2010-04-28	2012-07-10	Hoffmann-La Roche Inc.	Spiroindolinone pyrrolidines
TW201202246A (en) *	2010-05-28	2012-01-16	Biocryst Pharm Inc	Heterocyclic compounds as JANUS kinase inhibitors
US20120214830A1 (en)	2011-02-22	2012-08-23	OSI Pharmaceuticals, LLC	Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors in hepatocellular carcinoma
US9464079B2 (en)	2011-03-23	2016-10-11	Semorex Technologies Ltd.	Treatment of proliferative disorders with a chemiluminescent agent
WO2012149014A1 (en)	2011-04-25	2012-11-01	OSI Pharmaceuticals, LLC	Use of emt gene signatures in cancer drug discovery, diagnostics, and treatment
CA2839437A1 (en)	2011-06-16	2012-12-20	Isis Pharmaceuticals, Inc.	Antisense modulation of fibroblast growth factor receptor 4 expression
KR20140036269A (ko)	2011-07-01	2014-03-25	바이엘 인텔렉쳐 프로퍼티 게엠베하	Alk1 억제제로서의 히드록시메틸아릴-치환된 피롤로트리아진
AU2012308570B2 (en)	2011-09-14	2016-11-10	Samumed, Llc	Indazole-3-carboxamides and their use as Wnt/b-catenin signaling pathway inhibitors
UY34484A (es)	2011-12-15	2013-07-31	Bayer Ip Gmbh	Benzotienilo-pirrolotriazinas disustituidas y sus usos
US9598416B2 (en)	2011-12-15	2017-03-21	Bayer Intellectual Property Gmbh	Substituted benzothienyl-pyrrolotriazines and uses thereof in the treatment cancer
ES2581065T3 (es) *	2012-02-23	2016-08-31	Bayer Intellectual Property Gmbh	Benzotienil-pirrolotriazinas sustituidas y usos de las mismas
PH12017500997A1 (en)	2012-04-04	2018-02-19	Samumed Llc	Indazole inhibitors of the wnt signal pathway and therapeutic uses thereof
WO2013152252A1 (en)	2012-04-06	2013-10-10	OSI Pharmaceuticals, LLC	Combination anti-cancer therapy
CN102675323B (zh) *	2012-06-01	2014-04-09	南京药石药物研发有限公司	吡咯并[2,1-f][1,2,4]三嗪衍生物及其抗肿瘤用途
WO2014082230A1 (zh) *	2012-11-28	2014-06-05	上海希迈医药科技有限公司	吡咯并三嗪类衍生物、其制备方法及其在医药上的应用
CA2897400A1 (en)	2013-01-08	2014-07-17	Samumed, Llc	3-(benzoimidazol-2-yl)-indazole inhibitors of the wnt signaling pathway and therapeutic uses thereof
WO2014115171A1 (en) *	2013-01-24	2014-07-31	Council Of Scientific & Industrial Research	Triazine compounds and a process for preparation thereof
AU2014223548A1 (en)	2013-02-26	2015-10-15	Triact Therapeutics, Inc.	Cancer therapy
WO2014143606A1 (en) *	2013-03-11	2014-09-18	Bristol-Myers Squibb Company	Pyrrolotriazines as potassium ion channel inhibitors
WO2014143607A1 (en) *	2013-03-11	2014-09-18	Bristol-Myers Squibb Company	Pyrrolopyridazines as potassium ion channel inhibitors
US9050345B2 (en) *	2013-03-11	2015-06-09	Bristol-Myers Squibb Company	Pyrrolotriazines as potassium ion channel inhibitors
EP2970231A1 (en)	2013-03-15	2016-01-20	Blueprint Medicines Corporation	Piperazine derivatives and their use as kit modulators
US9381246B2 (en)	2013-09-09	2016-07-05	Triact Therapeutics, Inc.	Cancer therapy
US9334263B2 (en)	2013-10-17	2016-05-10	Blueprint Medicines Corporation	Compositions useful for treating disorders related to kit
RU2706235C2 (ru) *	2013-10-17	2019-11-15	Блюпринт Медсинс Корпорейшн	Композиции, пригодные для лечения расстройств, связанных с kit
WO2015081783A1 (zh) *	2013-12-06	2015-06-11	江苏奥赛康药业股份有限公司	吡咯并[2,1-f][1,2,4]三嗪类衍生物及其制备方法和用途
CN104725381B (zh) *	2013-12-19	2018-04-10	南京圣和药业股份有限公司	生长因子受体抑制剂及其应用
US9388239B2 (en)	2014-05-01	2016-07-12	Consejo Nacional De Investigation Cientifica	Anti-human VEGF antibodies with unusually strong binding affinity to human VEGF-A and cross reactivity to human VEGF-B
US9688680B2 (en)	2014-08-04	2017-06-27	Blueprint Medicines Corporation	Compositions useful for treating disorders related to kit
WO2016040193A1 (en)	2014-09-08	2016-03-17	Samumed, Llc	3-(1h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridine and therapeutic uses thereof
WO2016040182A1 (en)	2014-09-08	2016-03-17	Samumed, Llc	2-(1h-indazol-3-yl)-1h-imidazo[4,5-c]pyridine and therapeutic uses thereof
WO2016040181A1 (en)	2014-09-08	2016-03-17	Samumed, Llc	3-(1h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof
WO2016040188A1 (en)	2014-09-08	2016-03-17	Samumed, Llc	3-(3h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof
WO2016040180A1 (en)	2014-09-08	2016-03-17	Samumed, Llc	3-(1h-benzo[d]imidazol-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof
WO2016040190A1 (en)	2014-09-08	2016-03-17	Samumed, Llc	3-(3h-imidazo[4,5-b]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridine and therapeutic uses thereof
WO2016040184A1 (en)	2014-09-08	2016-03-17	Samumed, Llc	3-(3h-imidazo[4,5-b]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof
WO2016040185A1 (en)	2014-09-08	2016-03-17	Samumed, Llc	2-(1h-indazol-3-yl)-3h-imidazo[4,5-b]pyridine and therapeutic uses thereof
AR103636A1 (es)	2015-02-05	2017-05-24	Teva Pharmaceuticals Int Gmbh	Métodos de tratamiento de neuralgia postherpética con una formulación tópica de un compuesto de espiro-oxindol
CN104876935B (zh) *	2015-05-18	2017-04-19	南方医科大学	2‑氨基吡咯并[1,2‑f][1,2,4]三嗪类化合物、合成方法及应用
JP2018521076A (ja)	2015-07-24	2018-08-02	ブループリントメディシンズコーポレイション	Ｋｉｔ及びｐｄｇｆｒに関連する疾病を治療するのに有用な化合物
US10392383B2 (en)	2015-08-03	2019-08-27	Samumed, Llc	3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[4,3-b]pyridines and therapeutic uses thereof
WO2017024025A1 (en)	2015-08-03	2017-02-09	Sunil Kumar Kc	3-(1h-pyrrolo[2,3-c]pyridin-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof
WO2017023987A1 (en)	2015-08-03	2017-02-09	Samumed, Llc.	3-(1h-pyrrolo[3,2-c]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
WO2017023986A1 (en)	2015-08-03	2017-02-09	Samumed, Llc	3-(1h-indol-2-yl)-1h-indazoles and therapeutic uses thereof
WO2017023980A1 (en)	2015-08-03	2017-02-09	Samumed, Llc.	3-(1h-pyrrolo[2,3-b]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridines and therapeutic uses thereof
US10329309B2 (en)	2015-08-03	2019-06-25	Samumed, Llc	3-(3H-imidazo[4,5-B]pyridin-2-yl)-1H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof
WO2017023996A1 (en)	2015-08-03	2017-02-09	Samumed, Llc.	3-(1h-pyrrolo[2,3-b]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
US10195185B2 (en)	2015-08-03	2019-02-05	Samumed, Llc	3-(1H-imidazo[4,5-C]pyridin-2-yl)-1H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof
WO2017023993A1 (en)	2015-08-03	2017-02-09	Samumed, Llc.	3-(1h-indol-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof
WO2017024010A1 (en)	2015-08-03	2017-02-09	Samumed, Llc.	3-(1h-pyrrolo[3,2-c]pyridin-2-yl)-1h-indazoles and therapeutic uses thereof
WO2017024003A1 (en)	2015-08-03	2017-02-09	Samumed, Llc	3-(1h-pyrrolo[3,2-c]pyridin-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof
WO2017024021A1 (en)	2015-08-03	2017-02-09	Samumed, Llc	3-(1h-pyrrolo[2,3-b]pyridin-2-yl)-1h-indazoles and therapeutic uses thereof
WO2017023975A1 (en)	2015-08-03	2017-02-09	Samumed, Llc.	3-(1h-pyrrolo[2,3-c]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridines and therapeutic uses thereof
US10206908B2 (en)	2015-08-03	2019-02-19	Samumed, Llc	3-(1H-pyrrolo[3,2-C]pyridin-2-YL)-1H-pyrazolo[3,4-C]pyridines and therapeutic uses thereof
US10188634B2 (en)	2015-08-03	2019-01-29	Samumed, Llc	3-(3H-imidazo[4,5-C]pyridin-2-yl)-1 H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof
US10206909B2 (en)	2015-08-03	2019-02-19	Samumed, Llc	3-(1H-pyrrolo[2,3-B]pyridin-2-yl)-1H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof
WO2017024026A1 (en)	2015-08-03	2017-02-09	Samumed, Llc	3-(1h-indol-2-yl)-1h-pyrazolo[3,4-c]pyridines and therapeutic uses thereof
CN108472290A (zh)	2015-11-06	2018-08-31	萨穆梅德有限公司	治疗骨关节炎
AR108325A1 (es)	2016-04-27	2018-08-08	Samumed Llc	Isoquinolin-3-il carboxamidas y preparación y uso de las mismas
CA3021185C (en) *	2016-04-28	2024-06-04	Takeda Pharmaceutical Company Limited	Fused heterocyclic compound
PT3464285T (pt)	2016-06-01	2022-12-20	Biosplice Therapeutics Inc	Processo para preparar n-(5-(3-(7-(3-fluorofenil)-3himidazo[4,5-c]piridin-2-il)-1h-indazol-5-il)piridin-3-il)-3-metilbutanamida
RU2770613C2 (ru)	2016-10-21	2022-04-19	СЭМЬЮМЕД, ЭлЭлСи	Способы применения индазол-3-карбоксамидов и их применение в качестве ингибиторов сигнального пути wnt/в-катенина
WO2018085865A1 (en)	2016-11-07	2018-05-11	Samumed, Llc	Single-dose, ready-to-use injectable formulations
KR102398659B1 (ko) *	2017-03-17	2022-05-16	주식회사 대웅제약	카이네이즈 저해제로서의 피롤로트리아진 유도체
US11040979B2 (en)	2017-03-31	2021-06-22	Blueprint Medicines Corporation	Substituted pyrrolo[1,2-b]pyridazines for treating disorders related to KIT and PDGFR
WO2019201194A1 (zh)	2018-04-16	2019-10-24	深圳市塔吉瑞生物医药有限公司	取代的吡咯并三嗪类化合物及其药物组合物及其用途
CN113966334B (zh)	2019-04-12	2025-01-21	缆图药品公司	化合物(i)的晶体形式
JP7600140B2 (ja) *	2019-04-12	2024-12-16	ブループリントメディシンズコーポレイション	Ｋｉｔ及びｐｄｇｆｒａ媒介性疾患を治療するための組成物及び方法
WO2021094209A1 (en)	2019-11-12	2021-05-20	Bayer Aktiengesellschaft	Substituted pyrrolo triazine carboxamide derivatives as prostaglandin ep3 receptor antagonists
AU2023249795A1 (en)	2022-04-08	2024-10-17	Shy Therapeutics, Llc	Compounds that interact with ras superfamily proteins for treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease
WO2026019977A1 (en) *	2024-07-19	2026-01-22	Merck Sharp & Dohme Llc	Pyrrolopyridazine vegfr inhibitors
CN119285594A (zh) *	2024-09-25	2025-01-10	浙江大学金华研究院	7-氨基苯并吡喃酮或7-氨基喹啉酮类化合物及其应用

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
RU2057754C1 (ru) *	1989-06-05	1996-04-10	Дайити Фармасьютикал Ко., Лтд.	Гетероциклические соединения или их кислотно-аддитивные соли
RU2097384C1 (ru) *	1989-10-31	1997-11-27	Биокрист Фармасьютикалз Инк.	Производные 2-амино-7-(chr2r3)-3н,5н-пирроло[3,2-d]-пиримидин-4-она, способы их получения и способ селективного ингибирования пролиферации т-лимфоцитов млекопитающего и не оказывающий воздействия на b-лимфоциты
DE69529056T2 (de) *	1994-01-19	2003-11-13	Sankyo Co., Ltd.	Pyrrolopyridazin-derivate
ES2109796T3 (es) *	1994-05-03	1998-01-16	Ciba Geigy Ag	Derivados de pirrolopirimidilo con efecto antiproliferante.
GB9604361D0 (en) *	1996-02-29	1996-05-01	Pharmacia Spa	4-Substituted pyrrolopyrimidine compounds as tyrosine kinase inhibitors
EP1183033B1 (en) *	1999-05-21	2006-03-01	Bristol-Myers Squibb Company	Pyrrolotriazine inhibitors of kinases

2000
- 2000-05-16 EP EP00930761A patent/EP1183033B1/en not_active Expired - Lifetime
- 2000-05-16 WO PCT/US2000/013420 patent/WO2000071129A1/en not_active Ceased
- 2000-05-16 TR TR2001/03352T patent/TR200103352T2/xx unknown
- 2000-05-16 RU RU2001134899/04A patent/RU2331640C2/ru not_active IP Right Cessation
- 2000-05-16 DE DE60042620T patent/DE60042620D1/de not_active Expired - Lifetime
- 2000-05-16 PL PL351720A patent/PL204437B1/pl unknown
- 2000-05-16 BR BR0010482-5A patent/BR0010482A/pt not_active IP Right Cessation
- 2000-05-16 ES ES06003602T patent/ES2328269T3/es not_active Expired - Lifetime
- 2000-05-16 HU HU0301005A patent/HUP0301005A3/hu not_active Application Discontinuation
- 2000-05-16 DK DK00930761T patent/DK1183033T3/da active
- 2000-05-16 MX MXPA01011832A patent/MXPA01011832A/es active IP Right Grant
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- 2000-05-16 AT AT00930761T patent/ATE318603T1/de active
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2001
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Also Published As

Publication number	Publication date
CN1351498B (zh)	2012-08-15
RU2331640C2 (ru)	2008-08-20
TR200103352T2 (tr)	2005-03-21
DK1183033T3 (da)	2006-06-06
CA2373990C (en)	2007-05-08
NO20015650L (no)	2001-11-20
EP1183033A1 (en)	2002-03-06
WO2000071129A1 (en)	2000-11-30
NO20015650D0 (no)	2001-11-20
MXPA01011832A (es)	2002-06-21
JP2003500359A (ja)	2003-01-07
BR0010482A (pt)	2002-04-23
AR043087A1 (es)	2005-07-20
PE20010126A1 (es)	2001-04-22
HUP0301005A3 (en)	2006-05-29
IL144977A0 (en)	2002-06-30
JP4649046B2 (ja)	2011-03-09
CZ303660B6 (cs)	2013-02-13
PL351720A1 (en)	2003-06-02
DE60026297T2 (de)	2006-11-02
PL204437B1 (pl)	2010-01-29
KR20020015041A (ko)	2002-02-27
EP1183033A4 (en)	2002-07-17
HUP0301005A2 (hu)	2003-07-28
TWI238163B (en)	2005-08-21
NZ516292A (en)	2004-01-30
AU770377B2 (en)	2004-02-19
IL144977A (en)	2006-12-10
DE60042620D1 (de)	2009-09-03
UY26150A1 (es)	2000-12-29
HK1041599B (en)	2006-09-15
JP2011037878A (ja)	2011-02-24
HK1041599A1 (en)	2002-07-12
KR100666514B1 (ko)	2007-02-28
EG24027A (en)	2008-03-26
DE60026297D1 (de)	2006-04-27
MY128370A (en)	2007-01-31
ES2258459T3 (es)	2006-09-01
ATE318603T1 (de)	2006-03-15
EP1183033B1 (en)	2006-03-01
AU4852400A (en)	2000-12-12
ES2328269T3 (es)	2009-11-11
CN1351498A (zh)	2002-05-29
CA2373990A1 (en)	2000-11-30
CZ20014169A3 (cs)	2002-10-16

Publication	Publication Date	Title
NO322214B1 (no)	2006-08-28	Forbindelser som er pyrrolotriazin-inhibitorer for kinaser, farmasoytiske preparater omfattende forbindelsene, samt anvendelser derav for fremstilling av er farmasoytisk preparat.
US7244733B2 (en)	2007-07-17	Pyrrolotriazine inhibitors of kinases
KR100901939B1 (ko)	2009-06-10	신규한 키나제 억제제
US20040063708A1 (en)	2004-04-01	Pyrrolotriazine kinase inhibitors
KR20050044441A (ko)	2005-05-12	Ｃ-5 변형된 인다졸릴피롤로트리아진
EP1669071B1 (en)	2009-07-22	Pyrrolotriazine inhibitors of kinases
KR100869417B1 (ko)	2008-11-21	신규한 키나제 억제제
HK1092073A (en)	2007-02-02	Pyrrolotriazine inhibitors of kinases
ZA200109577B (en)	2003-02-20	Pyrrolotriazine inhibitors of kinases.

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