DE60314500T2 - Diaminopyrimidine und deren verwendung als angiogenesehemmer - Google Patents
Diaminopyrimidine und deren verwendung als angiogenesehemmer Download PDFInfo
- Publication number
- DE60314500T2 DE60314500T2 DE60314500T DE60314500T DE60314500T2 DE 60314500 T2 DE60314500 T2 DE 60314500T2 DE 60314500 T DE60314500 T DE 60314500T DE 60314500 T DE60314500 T DE 60314500T DE 60314500 T2 DE60314500 T2 DE 60314500T2
- Authority
- DE
- Germany
- Prior art keywords
- methyl
- amino
- pyrimidinyl
- phenyl
- benzimidazol
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Fee Related
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- YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical compound NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 title 1
- 101000753291 Homo sapiens Angiopoietin-1 receptor Proteins 0.000 claims abstract description 31
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- 238000011282 treatment Methods 0.000 claims abstract description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 25
- 229940091171 VEGFR-2 tyrosine kinase inhibitor Drugs 0.000 claims abstract description 4
- -1 -NR 8 R 9 Chemical group 0.000 claims description 463
- 150000001875 compounds Chemical class 0.000 claims description 399
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 199
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 178
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 123
- 125000000217 alkyl group Chemical group 0.000 claims description 117
- 229910052739 hydrogen Inorganic materials 0.000 claims description 96
- 239000001257 hydrogen Substances 0.000 claims description 91
- 150000002431 hydrogen Chemical group 0.000 claims description 67
- 150000003839 salts Chemical class 0.000 claims description 51
- 125000003118 aryl group Chemical group 0.000 claims description 44
- 239000012453 solvate Substances 0.000 claims description 38
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 36
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims description 31
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 31
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- 230000000694 effects Effects 0.000 claims description 29
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 28
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims description 27
- 229910052736 halogen Inorganic materials 0.000 claims description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims description 27
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 26
- 150000002367 halogens Chemical class 0.000 claims description 26
- 230000033115 angiogenesis Effects 0.000 claims description 25
- OWCDMRFUFMERMZ-UHFFFAOYSA-N benzenesulfonamide;hydrochloride Chemical compound Cl.NS(=O)(=O)C1=CC=CC=C1 OWCDMRFUFMERMZ-UHFFFAOYSA-N 0.000 claims description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- 206010028980 Neoplasm Diseases 0.000 claims description 24
- 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 claims description 23
- 125000001072 heteroaryl group Chemical group 0.000 claims description 23
- 239000000460 chlorine Substances 0.000 claims description 22
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 22
- 201000011510 cancer Diseases 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 19
- 102000009465 Growth Factor Receptors Human genes 0.000 claims description 16
- 108010009202 Growth Factor Receptors Proteins 0.000 claims description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 15
- 125000002252 acyl group Chemical group 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 125000004104 aryloxy group Chemical group 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 10
- 108091008605 VEGF receptors Proteins 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 239000003112 inhibitor Substances 0.000 claims description 10
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 8
- 125000003435 aroyl group Chemical group 0.000 claims description 8
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 8
- 125000001188 haloalkyl group Chemical group 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 7
- 102000001301 EGF receptor Human genes 0.000 claims description 7
- 108060006698 EGF receptor Proteins 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 6
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 6
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 5
- 125000001769 aryl amino group Chemical group 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 claims description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- RAJZBUQASUJFSW-UHFFFAOYSA-N CC1(NC2=C(N1C)C=CC(=C2)N(C2=NC(=NC=C2)NC2=CC(=CC=C2)CS(=O)(=O)C)C)N Chemical compound CC1(NC2=C(N1C)C=CC(=C2)N(C2=NC(=NC=C2)NC2=CC(=CC=C2)CS(=O)(=O)C)C)N RAJZBUQASUJFSW-UHFFFAOYSA-N 0.000 claims description 3
- GSFXWKHBUFXTRU-UHFFFAOYSA-N Cl.CC(C)(C)C1(NC2=C(N1C)C=CC(=C2)N(C2=NC(=NC=C2)NC2=CC=C(C=C2)CS(=O)(=O)C)C)N Chemical compound Cl.CC(C)(C)C1(NC2=C(N1C)C=CC(=C2)N(C2=NC(=NC=C2)NC2=CC=C(C=C2)CS(=O)(=O)C)C)N GSFXWKHBUFXTRU-UHFFFAOYSA-N 0.000 claims description 3
- VJGBWMCKULAWDV-UHFFFAOYSA-N Cl.CC(C)C1(NC2=C(N1)C=CC(=C2)NC2=NC(=NC=C2)NC2=CC=C(C=C2)CS(=O)(=O)C)N Chemical compound Cl.CC(C)C1(NC2=C(N1)C=CC(=C2)NC2=NC(=NC=C2)NC2=CC=C(C=C2)CS(=O)(=O)C)N VJGBWMCKULAWDV-UHFFFAOYSA-N 0.000 claims description 3
- LOFPNIQTLJLGID-UHFFFAOYSA-N Cl.CC1(NC2=C(N1C)C=CC(=C2)N(C2=NC(=NC=C2)NC2=CC=C(C=C2)CS(=O)(=O)C)C)N Chemical compound Cl.CC1(NC2=C(N1C)C=CC(=C2)N(C2=NC(=NC=C2)NC2=CC=C(C=C2)CS(=O)(=O)C)C)N LOFPNIQTLJLGID-UHFFFAOYSA-N 0.000 claims description 3
- XDRQSRSTPITXGL-UHFFFAOYSA-N Cl.CC1=CC=C(C=C1)CC1(NC2=C(N1)C=CC(=C2)NC2=NC(=NC=C2)NC2=CC(=CC=C2)CCS(=O)(=O)C)N Chemical compound Cl.CC1=CC=C(C=C1)CC1(NC2=C(N1)C=CC(=C2)NC2=NC(=NC=C2)NC2=CC(=CC=C2)CCS(=O)(=O)C)N XDRQSRSTPITXGL-UHFFFAOYSA-N 0.000 claims description 3
- HFOCPXSPTWQCBU-UHFFFAOYSA-N Cl.CC1=CC=C(C=C1)CC1(NC2=C(N1)C=CC(=C2)NC2=NC(=NC=C2)NC2=CC(=CC=C2)CS(=O)(=O)C)N Chemical compound Cl.CC1=CC=C(C=C1)CC1(NC2=C(N1)C=CC(=C2)NC2=NC(=NC=C2)NC2=CC(=CC=C2)CS(=O)(=O)C)N HFOCPXSPTWQCBU-UHFFFAOYSA-N 0.000 claims description 3
- SBYULYZXXGXONZ-UHFFFAOYSA-N Cl.CC1=CC=C(C=C1)CC1(NC2=C(N1)C=CC(=C2)NC2=NC(=NC=C2)NC2=CC=C(C=C2)CCS(=O)(=O)C)N Chemical compound Cl.CC1=CC=C(C=C1)CC1(NC2=C(N1)C=CC(=C2)NC2=NC(=NC=C2)NC2=CC=C(C=C2)CCS(=O)(=O)C)N SBYULYZXXGXONZ-UHFFFAOYSA-N 0.000 claims description 3
- VPSOQJCWGNJXCR-UHFFFAOYSA-N Cl.ClC1=CC=C(C=C1)CC1(NC2=C(N1C)C=CC(=C2)N(C2=NC(=NC=C2)NC2=CC=C(C=C2)CS(=O)(=O)C)C)N Chemical compound Cl.ClC1=CC=C(C=C1)CC1(NC2=C(N1C)C=CC(=C2)N(C2=NC(=NC=C2)NC2=CC=C(C=C2)CS(=O)(=O)C)C)N VPSOQJCWGNJXCR-UHFFFAOYSA-N 0.000 claims description 3
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 claims description 3
- 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 claims description 3
- 230000000118 anti-neoplastic effect Effects 0.000 claims description 3
- 238000011319 anticancer therapy Methods 0.000 claims description 3
- MIBFTLBYFXKULA-UHFFFAOYSA-N 2-cyclohexyl-5-N,1-dimethyl-5-N-[2-[4-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]-3H-benzimidazole-2,5-diamine Chemical compound C1(CCCCC1)C1(NC2=C(N1C)C=CC(=C2)N(C)C1=NC(=NC=C1)NC1=CC=C(C=C1)CS(=O)(=O)C)N MIBFTLBYFXKULA-UHFFFAOYSA-N 0.000 claims description 2
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 2
- 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 claims description 2
- 101000851030 Homo sapiens Vascular endothelial growth factor receptor 3 Proteins 0.000 claims description 2
- 229940124530 sulfonamide Drugs 0.000 claims description 2
- USJUUYYGHABIBU-UHFFFAOYSA-N methanesulfonamide;hydrochloride Chemical compound Cl.CS(N)(=O)=O USJUUYYGHABIBU-UHFFFAOYSA-N 0.000 claims 4
- XLZLNCSZYWPDRJ-UHFFFAOYSA-N ethanesulfonamide;hydrochloride Chemical compound Cl.CCS(N)(=O)=O XLZLNCSZYWPDRJ-UHFFFAOYSA-N 0.000 claims 3
- LJDJWSFXEMYELA-UHFFFAOYSA-N FC(C(=O)O)(F)F.C1(=CC=CC=C1)CS(=O)(=O)O Chemical compound FC(C(=O)O)(F)F.C1(=CC=CC=C1)CS(=O)(=O)O LJDJWSFXEMYELA-UHFFFAOYSA-N 0.000 claims 2
- 108010090091 TIE-2 Receptor Proteins 0.000 claims 2
- 102000012753 TIE-2 Receptor Human genes 0.000 claims 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims 2
- WRHUDFRWZFBPEF-UHFFFAOYSA-N methanesulfonamide;2,2,2-trifluoroacetic acid Chemical compound CS(N)(=O)=O.OC(=O)C(F)(F)F WRHUDFRWZFBPEF-UHFFFAOYSA-N 0.000 claims 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 2
- NIHHYKUHSZFXTC-UHFFFAOYSA-N (4-methoxyphenyl) carbamate Chemical compound COC1=CC=C(OC(N)=O)C=C1 NIHHYKUHSZFXTC-UHFFFAOYSA-N 0.000 claims 1
- XNCMQRWVMWLODV-UHFFFAOYSA-N 1-phenylbenzimidazole Chemical compound C1=NC2=CC=CC=C2N1C1=CC=CC=C1 XNCMQRWVMWLODV-UHFFFAOYSA-N 0.000 claims 1
- NYHUWXNDQAZDPK-UHFFFAOYSA-N 2-[4-[[4-[[2-[(3-fluorophenyl)methylamino]-1-methylbenzimidazol-5-yl]-methylamino]pyrimidin-2-yl]amino]phenyl]-n-methylethanesulfonamide;hydrochloride Chemical compound Cl.C1=CC(CCS(=O)(=O)NC)=CC=C1NC1=NC=CC(N(C)C=2C=C3N=C(NCC=4C=C(F)C=CC=4)N(C)C3=CC=2)=N1 NYHUWXNDQAZDPK-UHFFFAOYSA-N 0.000 claims 1
- IYECZNNMBACPSD-UHFFFAOYSA-N 2-[4-[[4-[[2-[(4-chlorophenyl)methylamino]-1-methylbenzimidazol-5-yl]-methylamino]pyrimidin-2-yl]amino]phenyl]-n-methylethanesulfonamide;hydrochloride Chemical compound Cl.C1=CC(CCS(=O)(=O)NC)=CC=C1NC1=NC=CC(N(C)C=2C=C3N=C(NCC=4C=CC(Cl)=CC=4)N(C)C3=CC=2)=N1 IYECZNNMBACPSD-UHFFFAOYSA-N 0.000 claims 1
- JPCFCNOWHUSYDM-UHFFFAOYSA-N 2-[4-[[4-[[2-[(4-fluorophenyl)methylamino]-1-methylbenzimidazol-5-yl]-methylamino]pyrimidin-2-yl]amino]phenyl]-n-methylethanesulfonamide;hydrochloride Chemical compound Cl.C1=CC(CCS(=O)(=O)NC)=CC=C1NC1=NC=CC(N(C)C=2C=C3N=C(NCC=4C=CC(F)=CC=4)N(C)C3=CC=2)=N1 JPCFCNOWHUSYDM-UHFFFAOYSA-N 0.000 claims 1
- RHMRHGLMZBCOKT-UHFFFAOYSA-N 2-methylbenzenesulfonamide;hydrochloride Chemical compound Cl.CC1=CC=CC=C1S(N)(=O)=O RHMRHGLMZBCOKT-UHFFFAOYSA-N 0.000 claims 1
- CYDFLMAUWNCQTJ-UHFFFAOYSA-N 5-[[4-[[2-(4-fluoroanilino)-1-methylbenzimidazol-5-yl]-methylamino]pyrimidin-2-yl]amino]-2-methylbenzenesulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=NC(NC=2C=C(C(C)=CC=2)S(N)(=O)=O)=NC=1N(C)C(C=C1N=2)=CC=C1N(C)C=2NC1=CC=C(F)C=C1 CYDFLMAUWNCQTJ-UHFFFAOYSA-N 0.000 claims 1
- MMXUAMZMIXZKFR-UHFFFAOYSA-N 5-[[4-[[2-(4-tert-butylanilino)-1-methylbenzimidazol-5-yl]-methylamino]pyrimidin-2-yl]amino]-2-methylbenzenesulfonamide;hydrochloride Chemical compound Cl.C=1C=NC(NC=2C=C(C(C)=CC=2)S(N)(=O)=O)=NC=1N(C)C(C=C1N=2)=CC=C1N(C)C=2NC1=CC=C(C(C)(C)C)C=C1 MMXUAMZMIXZKFR-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- 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
- C07D401/14—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 three or more hetero rings
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- 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
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Vascular Medicine (AREA)
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- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36074102P | 2002-03-01 | 2002-03-01 | |
| US360741P | 2002-03-01 | ||
| PCT/US2003/006022 WO2003074515A1 (en) | 2002-03-01 | 2003-02-28 | Diamino-pyrimidines and their use as angiogenesis inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60314500D1 DE60314500D1 (de) | 2007-08-02 |
| DE60314500T2 true DE60314500T2 (de) | 2008-02-07 |
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| Application Number | Title | Priority Date | Filing Date |
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| DE60314500T Expired - Fee Related DE60314500T2 (de) | 2002-03-01 | 2003-02-28 | Diaminopyrimidine und deren verwendung als angiogenesehemmer |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US7338959B2 (enExample) |
| EP (1) | EP1487824B1 (enExample) |
| JP (1) | JP2005524668A (enExample) |
| AT (1) | ATE365165T1 (enExample) |
| AU (1) | AU2003220970A1 (enExample) |
| CA (1) | CA2477505A1 (enExample) |
| DE (1) | DE60314500T2 (enExample) |
| ES (1) | ES2290479T3 (enExample) |
| MX (1) | MXPA04008458A (enExample) |
| WO (1) | WO2003074515A1 (enExample) |
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| TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| EA007987B1 (ru) * | 2002-03-29 | 2007-02-27 | Чирон Корпорейшн | Замещённые бензазолы и их применение в качестве ингибиторов киназы raf |
| IL166241A0 (en) | 2002-07-29 | 2006-01-15 | Rigel Pharmaceuticals Inc | Method of treating or preventing autoimmune diseases with 2,4-pyrimidinedinediamine compounds |
| US20050282814A1 (en) * | 2002-10-03 | 2005-12-22 | Targegen, Inc. | Vasculostatic agents and methods of use thereof |
| US7531553B2 (en) * | 2003-03-21 | 2009-05-12 | Amgen Inc. | Heterocyclic compounds and methods of use |
| WO2004087153A2 (en) * | 2003-03-28 | 2004-10-14 | Chiron Corporation | Use of organic compounds for immunopotentiation |
| RS53109B (sr) | 2003-07-30 | 2014-06-30 | Rigel Pharmaceuticals Inc. | Jedinjenja 2,4 pirimidindiamina za upotrebu u tretmanu ili prevenciji autoimunih bolesti |
| DE10337942A1 (de) * | 2003-08-18 | 2005-03-17 | Merck Patent Gmbh | Aminobenzimidazolderivate |
| DE10342503A1 (de) * | 2003-09-12 | 2005-04-14 | Merck Patent Gmbh | Benzyl-Benzimidazolylderivate |
| CA2538413A1 (en) * | 2003-09-18 | 2005-03-24 | Novartis Ag | 2,4-di (phenylamino) pyrimidines useful in the treatment of proliferative disorders |
| DE10349587A1 (de) * | 2003-10-24 | 2005-05-25 | Merck Patent Gmbh | Benzimidazolylderivate |
| US7977322B2 (en) | 2004-08-20 | 2011-07-12 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-binding cassette transporters |
| EP1716122B1 (en) * | 2004-01-30 | 2017-04-19 | Vertex Pharmaceuticals Incorporated | Modulators of atp-binding cassette transporters |
| US20050209284A1 (en) * | 2004-02-12 | 2005-09-22 | Boehringer Ingelheim Pharmaceuticals, Inc. | Tec kinase inhibitors |
| NZ551027A (en) | 2004-04-08 | 2011-01-28 | Targegen Inc | Benzotriazine inhibitors of kinases |
| PL382308A1 (pl) | 2004-08-25 | 2007-08-20 | Targegen, Inc. | Związki heterocykliczne i sposoby stosowania |
| CN101039919A (zh) | 2004-10-13 | 2007-09-19 | 惠氏公司 | 经n－苯磺酰基取代的苯胺基嘧啶类似物 |
| ES2380550T3 (es) | 2004-11-24 | 2012-05-16 | Rigel Pharmaceuticals, Inc. | Compuestos de espiro-2,4-pirimidindiamina y sus usos |
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| EP1674470A1 (en) * | 2004-12-22 | 2006-06-28 | Schering Aktiengesellschaft | Sulfonamido-macrocycles as Tie2 inhibitors |
| EP1674466A1 (en) * | 2004-12-27 | 2006-06-28 | 4Sc Ag | 2,5- and 2,6-disubstituted benzazole analogues useful as protein kinase inhibitors |
| US7576090B2 (en) | 2004-12-27 | 2009-08-18 | 4Sc Ag | Benzazole analogues and uses thereof |
| NZ555947A (en) | 2005-01-19 | 2010-11-26 | Rigel Pharmaceuticals Inc | Prodrugs of 2,4-pyrimidinediamine compounds and their uses |
| US20060247263A1 (en) * | 2005-04-19 | 2006-11-02 | Amgen Inc. | Substituted heterocyclic compounds and methods of use |
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| JP2008543775A (ja) * | 2005-06-08 | 2008-12-04 | ターゲジェン インコーポレーティッド | 眼の障害を治療するための方法および組成物 |
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| MY167260A (en) * | 2005-11-01 | 2018-08-14 | Targegen Inc | Bi-aryl meta-pyrimidine inhibitors of kinases |
| US8604042B2 (en) * | 2005-11-01 | 2013-12-10 | Targegen, Inc. | Bi-aryl meta-pyrimidine inhibitors of kinases |
| US20070149508A1 (en) * | 2005-11-02 | 2007-06-28 | Targegen, Inc. | Six membered heteroaromatic inhibitors targeting resistant kinase mutations |
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| EA200802058A1 (ru) | 2006-05-09 | 2009-06-30 | Пфайзер Продактс Инк. | Производные циклоалкиламинокислот и их фармацевтические композиции |
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| CA2684470C (en) | 2007-04-16 | 2016-02-09 | Hutchison Medipharma Enterprises Limited | Pyrimidine derivatives |
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| EP2181987B9 (en) * | 2007-08-23 | 2014-09-03 | Takeda Pharmaceutical Company Limited | 2-Carbonylaminobenzothiazoles and their use for the prophylaxis and treatment of cancer |
| WO2009036066A1 (en) * | 2007-09-10 | 2009-03-19 | Curis, Inc. | Vegfr inhibitors containing a zinc binding moiety |
| KR20100132550A (ko) | 2008-04-16 | 2010-12-17 | 포톨라 파마슈티컬스, 인코포레이티드 | ｓｙｋ 또는 ＪＡＫ 키나제 억제제로서의 ２,６－디아미노-피리미딘－５－일－카르복스아미드 |
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| CZ302548B6 (cs) * | 2008-10-22 | 2011-07-07 | Zentiva, A.S. | Zpusob výroby 5-amino-2-[(4-methoxy-3-methyl-2-pyridyl)methylthio]-1H-benzimidazolu a 5-(1H-pyrrol-1-yl)-2-[(4-methoxy-3-methyl-2-pyridyl)methylthio]-1H-benzimidazolu |
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| JO3101B1 (ar) | 2008-12-02 | 2017-09-20 | Takeda Pharmaceuticals Co | مشتقات بنزوثيازول كعوامل مضادة للسرطان |
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| CN102459236B (zh) * | 2009-05-27 | 2014-10-29 | Abbvie公司 | 激酶活性的嘧啶抑制剂 |
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| GB9523675D0 (en) * | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| EP1109555A4 (en) | 1998-08-31 | 2001-11-21 | Merck & Co Inc | Novel angiogenesis inhibitors |
| DK1343782T3 (da) * | 2000-12-21 | 2009-08-24 | Smithkline Beecham Corp | Pyrimidinaminer som angiogenesemodulatorer |
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- 2003-02-28 CA CA002477505A patent/CA2477505A1/en not_active Abandoned
- 2003-02-28 AT AT03743709T patent/ATE365165T1/de not_active IP Right Cessation
- 2003-02-28 EP EP03743709A patent/EP1487824B1/en not_active Expired - Lifetime
- 2003-02-28 AU AU2003220970A patent/AU2003220970A1/en not_active Abandoned
- 2003-02-28 WO PCT/US2003/006022 patent/WO2003074515A1/en not_active Ceased
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| JP2005524668A (ja) | 2005-08-18 |
| EP1487824A1 (en) | 2004-12-22 |
| ATE365165T1 (de) | 2007-07-15 |
| DE60314500D1 (de) | 2007-08-02 |
| US20050234083A1 (en) | 2005-10-20 |
| AU2003220970A1 (en) | 2003-09-16 |
| WO2003074515A1 (en) | 2003-09-12 |
| EP1487824B1 (en) | 2007-06-20 |
| US7338959B2 (en) | 2008-03-04 |
| CA2477505A1 (en) | 2003-09-12 |
| MXPA04008458A (es) | 2004-12-06 |
| ES2290479T3 (es) | 2008-02-16 |
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| 8381 | Inventor (new situation) |
Inventor name: CHAMBERLAIN, STANLEY DAWES, RESEARCH TRIANGLE , US Inventor name: CHEUNG, MUI, RESEARCH TRIANGLE PARK, NC 27709, US Inventor name: EMERSON, HOLLY KATHLEEN, RESEARCH TRIANGLE PAR, US Inventor name: JOHNSON, NEIL W., RESEARCH TRIANGLE PARK, NC 2, US Inventor name: NAILOR, KRISTEN ELIZABETH, RESEARCH TRIANGLE P, US Inventor name: SAMMOND, DOUGLAS MCCORD, RESEARCH TRIANGLE PAR, US Inventor name: SEMONES, MARCUS, RESEARCH TRIANGLE PARK, NC 27, US |
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| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |