JP2002516327A - 細胞増殖の阻害剤としての二環式ピリミジンおよび二環式３，４−ジヒドロピリミジン - Google Patents
細胞増殖の阻害剤としての二環式ピリミジンおよび二環式３，４−ジヒドロピリミジンInfo
- Publication number
- JP2002516327A JP2002516327A JP2000550849A JP2000550849A JP2002516327A JP 2002516327 A JP2002516327 A JP 2002516327A JP 2000550849 A JP2000550849 A JP 2000550849A JP 2000550849 A JP2000550849 A JP 2000550849A JP 2002516327 A JP2002516327 A JP 2002516327A
- Authority
- JP
- Japan
- Prior art keywords
- pyrimido
- pyrimidin
- phenylamino
- dihydro
- phenyl
- 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.)
- Abandoned
Links
- -1 Bicyclic pyrimidines Chemical class 0.000 title claims description 226
- 239000003112 inhibitor Substances 0.000 title abstract description 15
- 230000010261 cell growth Effects 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 235
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 57
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 36
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 24
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 20
- 108091000080 Phosphotransferase Proteins 0.000 claims abstract description 16
- 102000020233 phosphotransferase Human genes 0.000 claims abstract description 16
- 230000002062 proliferating effect Effects 0.000 claims abstract description 16
- 102000003903 Cyclin-dependent kinases Human genes 0.000 claims abstract description 14
- 108090000266 Cyclin-dependent kinases Proteins 0.000 claims abstract description 14
- 201000011510 cancer Diseases 0.000 claims abstract description 14
- 239000001257 hydrogen Substances 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 14
- 230000033115 angiogenesis Effects 0.000 claims abstract description 12
- 208000037803 restenosis Diseases 0.000 claims abstract description 11
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 10
- 239000003102 growth factor Substances 0.000 claims abstract description 9
- 230000001404 mediated effect Effects 0.000 claims abstract description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000003085 diluting agent Substances 0.000 claims abstract description 6
- 239000003937 drug carrier Substances 0.000 claims abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 48
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 42
- 229910052757 nitrogen Inorganic materials 0.000 claims description 40
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 38
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
- 229910052760 oxygen Inorganic materials 0.000 claims description 28
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 150000002367 halogens Chemical class 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 24
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 claims description 23
- 125000003545 alkoxy group Chemical group 0.000 claims description 22
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 21
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 21
- 239000002253 acid Chemical class 0.000 claims description 20
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 19
- 125000005842 heteroatom Chemical group 0.000 claims description 18
- 230000002401 inhibitory effect Effects 0.000 claims description 18
- 201000010099 disease Diseases 0.000 claims description 16
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 15
- 239000011593 sulfur Substances 0.000 claims description 15
- 150000003573 thiols Chemical class 0.000 claims description 15
- 125000004001 thioalkyl group Chemical group 0.000 claims description 14
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 11
- 101150073031 cdk2 gene Proteins 0.000 claims description 11
- 101100005789 Caenorhabditis elegans cdk-4 gene Proteins 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 125000000304 alkynyl group Chemical group 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 150000002466 imines Chemical class 0.000 claims description 10
- 108050007372 Fibroblast Growth Factor Proteins 0.000 claims description 9
- 102000018233 Fibroblast Growth Factor Human genes 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- 229940126864 fibroblast growth factor Drugs 0.000 claims description 9
- LPUCHTNHUHOTRY-UHFFFAOYSA-N 1-(3-bicyclo[2.2.1]heptanyl)ethanamine Chemical compound C1CC2C(C(N)C)CC1C2 LPUCHTNHUHOTRY-UHFFFAOYSA-N 0.000 claims description 8
- 101150012716 CDK1 gene Proteins 0.000 claims description 8
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims description 8
- 230000004663 cell proliferation Effects 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 150000002825 nitriles Chemical class 0.000 claims description 8
- 150000002829 nitrogen Chemical class 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 101100059559 Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) nimX gene Proteins 0.000 claims description 7
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims description 7
- 101100273808 Xenopus laevis cdk1-b gene Proteins 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 150000002923 oximes Chemical class 0.000 claims description 7
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 7
- 125000000872 2-diethylaminoethoxy group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 6
- 201000004681 Psoriasis Diseases 0.000 claims description 6
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 6
- 210000004509 vascular smooth muscle cell Anatomy 0.000 claims description 6
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 5
- 102000037979 non-receptor tyrosine kinases Human genes 0.000 claims description 5
- 108091008046 non-receptor tyrosine kinases Proteins 0.000 claims description 5
- 125000005518 carboxamido group Chemical group 0.000 claims description 4
- OOJYJQIMJKZUSJ-UHFFFAOYSA-N 1-(3-bicyclo[2.2.1]heptanyl)-7-[4-(4-methylpiperazin-1-yl)anilino]pyrimido[4,5-d]pyrimidin-2-one Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=NC(=O)N2C3C4CCC(C4)C3)C2=N1 OOJYJQIMJKZUSJ-UHFFFAOYSA-N 0.000 claims description 3
- WGFUGBMZQCPOMB-UHFFFAOYSA-N 1-methyl-7-(4-pyrazol-1-ylanilino)pyrimido[4,5-d]pyrimidin-2-one Chemical compound N=1C=C2C=NC(=O)N(C)C2=NC=1NC(C=C1)=CC=C1N1C=CC=N1 WGFUGBMZQCPOMB-UHFFFAOYSA-N 0.000 claims description 3
- KAHIEOWPOWHUDI-UHFFFAOYSA-N 1-methyl-7-[4-(4-methylpiperazin-1-yl)anilino]pyrimido[4,5-d]pyrimidin-2-one Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=NC(=O)N2C)C2=N1 KAHIEOWPOWHUDI-UHFFFAOYSA-N 0.000 claims description 3
- KQYRLYXVCBSQJQ-UHFFFAOYSA-N 2-[4-(4-hydroxypiperidin-1-yl)anilino]-8-methyl-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N1=C2N(C)C(=O)NCC2=CN=C1NC(C=C1)=CC=C1N1CCC(O)CC1 KQYRLYXVCBSQJQ-UHFFFAOYSA-N 0.000 claims description 3
- QIEARILFCPQQSI-UHFFFAOYSA-N 2-[4-[4-(dimethylamino)piperidin-1-yl]anilino]-8-methyl-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound C1CC(N(C)C)CCN1C(C=C1)=CC=C1NC1=NC=C(CNC(=O)N2C)C2=N1 QIEARILFCPQQSI-UHFFFAOYSA-N 0.000 claims description 3
- JJRJEVUSKRUNDL-UHFFFAOYSA-N 2-[4-[4-(dimethylamino)piperidin-1-yl]anilino]-8-propan-2-yl-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N1=C2N(C(C)C)C(=O)NCC2=CN=C1NC(C=C1)=CC=C1N1CCC(N(C)C)CC1 JJRJEVUSKRUNDL-UHFFFAOYSA-N 0.000 claims description 3
- AKJJXTNCIMJSTI-UHFFFAOYSA-N 7-[4-(4-methylpiperazin-1-yl)anilino]-1-propan-2-ylpyrimido[4,5-d]pyrimidin-2-one Chemical compound N=1C=C2C=NC(=O)N(C(C)C)C2=NC=1NC(C=C1)=CC=C1N1CCN(C)CC1 AKJJXTNCIMJSTI-UHFFFAOYSA-N 0.000 claims description 3
- NIZHMCZGWWIWKG-UHFFFAOYSA-N 7-[4-[2-(diethylamino)ethoxy]anilino]-3-(3,5-dimethoxyphenyl)-1-ethyl-4h-pyrimido[4,5-d]pyrimidin-2-one Chemical compound C1=CC(OCCN(CC)CC)=CC=C1NC1=NC=C(CN(C(=O)N2CC)C=3C=C(OC)C=C(OC)C=3)C2=N1 NIZHMCZGWWIWKG-UHFFFAOYSA-N 0.000 claims description 3
- BPGHVIYMZOHLEA-UHFFFAOYSA-N 7-[4-[4-(3-morpholin-4-ylpropyl)piperidin-1-yl]anilino]-1-propan-2-ylpyrimido[4,5-d]pyrimidin-2-one Chemical compound N=1C=C2C=NC(=O)N(C(C)C)C2=NC=1NC(C=C1)=CC=C1N(CC1)CCC1CCCN1CCOCC1 BPGHVIYMZOHLEA-UHFFFAOYSA-N 0.000 claims description 3
- IDENZAFGZDVXKB-UHFFFAOYSA-N 7-[4-[4-(dimethylamino)piperidin-1-yl]anilino]-1-methylpyrimido[4,5-d]pyrimidin-2-one Chemical compound C1CC(N(C)C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=NC(=O)N2C)C2=N1 IDENZAFGZDVXKB-UHFFFAOYSA-N 0.000 claims description 3
- KQWHLVPKNZXXEV-UHFFFAOYSA-N 7-[4-[4-(dimethylamino)piperidin-1-yl]anilino]-1-propan-2-ylpyrimido[4,5-d]pyrimidin-2-one Chemical compound N=1C=C2C=NC(=O)N(C(C)C)C2=NC=1NC(C=C1)=CC=C1N1CCC(N(C)C)CC1 KQWHLVPKNZXXEV-UHFFFAOYSA-N 0.000 claims description 3
- CKEBVRPXMIKWIP-UHFFFAOYSA-N 8-methyl-2-(4-pyrazol-1-ylanilino)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N1=C2N(C)C(=O)NCC2=CN=C1NC(C=C1)=CC=C1N1C=CC=N1 CKEBVRPXMIKWIP-UHFFFAOYSA-N 0.000 claims description 3
- QQOUBGFAMSXQJP-UHFFFAOYSA-N 8-propan-2-yl-2-(4-pyrazol-1-ylanilino)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N1=C2N(C(C)C)C(=O)NCC2=CN=C1NC(C=C1)=CC=C1N1C=CC=N1 QQOUBGFAMSXQJP-UHFFFAOYSA-N 0.000 claims description 3
- 108700020796 Oncogene Proteins 0.000 claims description 3
- 206010057469 Vascular stenosis Diseases 0.000 claims description 3
- 239000004202 carbamide Substances 0.000 claims description 3
- 230000002980 postoperative effect Effects 0.000 claims description 3
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 3
- LDGZHKKSDWYYBA-UHFFFAOYSA-N 1-(3,5-dimethylheptyl)-7-[4-(4-methylpiperazin-1-yl)anilino]-3,4-dihydropyrido[4,3-d]pyrimidin-2-one Chemical compound C1=C2N(CCC(C)CC(C)CC)C(=O)NCC2=CN=C1NC(C=C1)=CC=C1N1CCN(C)CC1 LDGZHKKSDWYYBA-UHFFFAOYSA-N 0.000 claims description 2
- OWTGPKDIDKXNHZ-UHFFFAOYSA-N 1-(3-bicyclo[2.2.1]heptanyl)-7-(4-pyrazol-1-ylanilino)pyrimido[4,5-d]pyrimidin-2-one Chemical compound N1=C2N(C3C4CCC(C4)C3)C(=O)N=CC2=CN=C1NC(C=C1)=CC=C1N1C=CC=N1 OWTGPKDIDKXNHZ-UHFFFAOYSA-N 0.000 claims description 2
- VRKQHBMOSLPUBQ-UHFFFAOYSA-N 1-(3-bicyclo[2.2.1]heptanyl)-7-[4-(4-hydroxypiperidin-1-yl)anilino]pyrimido[4,5-d]pyrimidin-2-one Chemical compound C1CC(O)CCN1C(C=C1)=CC=C1NC1=NC=C(C=NC(=O)N2C3C4CCC(C4)C3)C2=N1 VRKQHBMOSLPUBQ-UHFFFAOYSA-N 0.000 claims description 2
- WVONWGTWBWLAOJ-UHFFFAOYSA-N 1-(3-bicyclo[2.2.1]heptanyl)-7-[4-[4-(dimethylamino)piperidin-1-yl]anilino]pyrimido[4,5-d]pyrimidin-2-one Chemical compound C1CC(N(C)C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=NC(=O)N2C3C4CCC(C4)C3)C2=N1 WVONWGTWBWLAOJ-UHFFFAOYSA-N 0.000 claims description 2
- ZZADPTLVHZAONE-UHFFFAOYSA-N 1-(3-hydroxypropyl)-7-[4-(4-methylpiperazin-1-yl)anilino]-3,4-dihydropyrido[4,3-d]pyrimidin-2-one Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC(N=C1)=CC2=C1CNC(=O)N2CCCO ZZADPTLVHZAONE-UHFFFAOYSA-N 0.000 claims description 2
- FOTIWFNYARKEJV-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)anilino]-5,8-dihydropyrimido[4,5-d]pyrimidin-7-yl]-3-propan-2-ylurea Chemical compound N=1C=C2CNC(NC(=O)NC(C)C)=NC2=NC=1NC(C=C1)=CC=C1N1CCN(C(C)=O)CC1 FOTIWFNYARKEJV-UHFFFAOYSA-N 0.000 claims description 2
- ITWZTPZSUCXFBF-UHFFFAOYSA-N 1-[3-(2-chloro-3,5-dimethoxyphenyl)-7-(pyridin-4-ylamino)-4h-pyrimido[4,5-d]pyrimidin-2-yl]-3-ethylurea Chemical compound N=1C=C2CN(C=3C(=C(OC)C=C(OC)C=3)Cl)C(NC(=O)NCC)=NC2=NC=1NC1=CC=NC=C1 ITWZTPZSUCXFBF-UHFFFAOYSA-N 0.000 claims description 2
- XIBHMIOBBVHSOX-UHFFFAOYSA-N 1-[3-(2-chloro-3,5-dimethoxyphenyl)-7-[4-(diethylamino)butylamino]-4h-pyrimido[4,5-d]pyrimidin-2-yl]-3-ethylurea Chemical compound CCNC(=O)NC1=NC2=NC(NCCCCN(CC)CC)=NC=C2CN1C1=CC(OC)=CC(OC)=C1Cl XIBHMIOBBVHSOX-UHFFFAOYSA-N 0.000 claims description 2
- JMNNHVDOWHBZGS-UHFFFAOYSA-N 1-[3-(2-chloro-3,5-dimethoxyphenyl)-7-[4-[2-(diethylamino)ethoxy]anilino]-4h-pyrimido[4,5-d]pyrimidin-2-yl]-3-ethylurea Chemical compound N=1C=C2CN(C=3C(=C(OC)C=C(OC)C=3)Cl)C(NC(=O)NCC)=NC2=NC=1NC1=CC=C(OCCN(CC)CC)C=C1 JMNNHVDOWHBZGS-UHFFFAOYSA-N 0.000 claims description 2
- VZXMDOYQIUIEJB-UHFFFAOYSA-N 1-[3-(3,5-dimethoxyphenyl)-7-(pyridin-4-ylamino)-4h-pyrimido[4,5-d]pyrimidin-2-yl]-3-ethylurea Chemical compound N=1C=C2CN(C=3C=C(OC)C=C(OC)C=3)C(NC(=O)NCC)=NC2=NC=1NC1=CC=NC=C1 VZXMDOYQIUIEJB-UHFFFAOYSA-N 0.000 claims description 2
- PYVOKPNSBSGKEP-UHFFFAOYSA-N 1-[3-(dimethylamino)propyl]-7-[4-(4-methylpiperazin-1-yl)anilino]-3,4-dihydropyrido[4,3-d]pyrimidin-2-one Chemical compound C1=C2N(CCCN(C)C)C(=O)NCC2=CN=C1NC(C=C1)=CC=C1N1CCN(C)CC1 PYVOKPNSBSGKEP-UHFFFAOYSA-N 0.000 claims description 2
- JMZBFDDWDQKWEU-UHFFFAOYSA-N 1-[3-(dimethylamino)propyl]-7-[4-(4-methylpiperazin-1-yl)anilino]pyrido[4,3-d]pyrimidin-2-one Chemical compound N=1C=C2C=NC(=O)N(CCCN(C)C)C2=CC=1NC(C=C1)=CC=C1N1CCN(C)CC1 JMZBFDDWDQKWEU-UHFFFAOYSA-N 0.000 claims description 2
- QUAQRTRBWXHSIP-UHFFFAOYSA-N 1-[7-(4-fluoroanilino)pyrimido[4,5-d]pyrimidin-2-yl]-3-methylurea Chemical compound N=1C2=NC(NC(=O)NC)=NC=C2C=NC=1NC1=CC=C(F)C=C1 QUAQRTRBWXHSIP-UHFFFAOYSA-N 0.000 claims description 2
- FAKVFHGYAUSYSU-UHFFFAOYSA-N 1-[7-(4-piperazin-1-ylanilino)pyrimido[4,5-d]pyrimidin-2-yl]-3-propan-2-ylurea Chemical compound N=1C2=NC(NC(=O)NC(C)C)=NC=C2C=NC=1NC(C=C1)=CC=C1N1CCNCC1 FAKVFHGYAUSYSU-UHFFFAOYSA-N 0.000 claims description 2
- DGMQKVSTMNWHCW-UHFFFAOYSA-N 1-[7-[4-(4-acetylpiperazin-1-yl)anilino]pyrimido[4,5-d]pyrimidin-2-yl]-3-propan-2-ylurea Chemical compound N=1C2=NC(NC(=O)NC(C)C)=NC=C2C=NC=1NC(C=C1)=CC=C1N1CCN(C(C)=O)CC1 DGMQKVSTMNWHCW-UHFFFAOYSA-N 0.000 claims description 2
- SFBNZVATRDLUJJ-UHFFFAOYSA-N 1-[7-[4-[2-(diethylamino)ethoxy]anilino]-3-(3,5-dimethoxyphenyl)-4h-pyrimido[4,5-d]pyrimidin-2-yl]-3-ethylurea Chemical compound N=1C=C2CN(C=3C=C(OC)C=C(OC)C=3)C(NC(=O)NCC)=NC2=NC=1NC1=CC=C(OCCN(CC)CC)C=C1 SFBNZVATRDLUJJ-UHFFFAOYSA-N 0.000 claims description 2
- PJOJHRHUSQPXIS-UHFFFAOYSA-N 1-[7-[4-[3-(aminomethyl)pyrrolidin-1-yl]anilino]pyrimido[4,5-d]pyrimidin-2-yl]-3-propan-2-ylurea Chemical compound N=1C2=NC(NC(=O)NC(C)C)=NC=C2C=NC=1NC(C=C1)=CC=C1N1CCC(CN)C1 PJOJHRHUSQPXIS-UHFFFAOYSA-N 0.000 claims description 2
- HSHLNEJOCHYTQO-UHFFFAOYSA-N 1-cyclopentyl-7-(4-piperazin-1-ylanilino)pyrido[4,3-d]pyrimidin-2-one Chemical compound C1=C2N(C3CCCC3)C(=O)N=CC2=CN=C1NC(C=C1)=CC=C1N1CCNCC1 HSHLNEJOCHYTQO-UHFFFAOYSA-N 0.000 claims description 2
- SIIGOVZBTPGWRM-UHFFFAOYSA-N 1-cyclopentyl-7-(4-piperazin-1-ylanilino)pyrimido[4,5-d]pyrimidin-2-one Chemical compound N1=C2N(C3CCCC3)C(=O)N=CC2=CN=C1NC(C=C1)=CC=C1N1CCNCC1 SIIGOVZBTPGWRM-UHFFFAOYSA-N 0.000 claims description 2
- CETJKWMLOZBBRP-UHFFFAOYSA-N 1-cyclopentyl-7-[4-(2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)anilino]pyrimido[4,5-d]pyrimidin-2-one Chemical compound C1C2CN(C)CC2CN1C(C=C1)=CC=C1NC(N=C12)=NC=C1C=NC(=O)N2C1CCCC1 CETJKWMLOZBBRP-UHFFFAOYSA-N 0.000 claims description 2
- CYLYLWLMVRIMFM-UHFFFAOYSA-N 1-hexa-2,4-dienyl-7-[4-(4-methylpiperazin-1-yl)anilino]-3,4-dihydropyrido[4,3-d]pyrimidin-2-one Chemical compound C1=C2N(CC=CC=CC)C(=O)NCC2=CN=C1NC(C=C1)=CC=C1N1CCN(C)CC1 CYLYLWLMVRIMFM-UHFFFAOYSA-N 0.000 claims description 2
- IMKFEYLQHSBAQD-UHFFFAOYSA-N 1-methyl-7-[4-[4-(3-morpholin-4-ylpropyl)piperidin-1-yl]anilino]pyrimido[4,5-d]pyrimidin-2-one Chemical compound N=1C=C2C=NC(=O)N(C)C2=NC=1NC(C=C1)=CC=C1N(CC1)CCC1CCCN1CCOCC1 IMKFEYLQHSBAQD-UHFFFAOYSA-N 0.000 claims description 2
- URBNLZHSLIHZBI-UHFFFAOYSA-N 1-tert-butyl-3-[3-(2-chloro-3,5-dimethoxyphenyl)-7-(pyridin-4-ylamino)-4h-pyrimido[4,5-d]pyrimidin-2-yl]urea Chemical compound COC1=CC(OC)=C(Cl)C(N2C(=NC3=NC(NC=4C=CN=CC=4)=NC=C3C2)NC(=O)NC(C)(C)C)=C1 URBNLZHSLIHZBI-UHFFFAOYSA-N 0.000 claims description 2
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- 125000006000 trichloroethyl group Chemical group 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229910000166 zirconium phosphate Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8670898P | 1998-05-26 | 1998-05-26 | |
| US60/086,708 | 1998-05-26 | ||
| US12615899P | 1999-03-25 | 1999-03-25 | |
| US60/126,158 | 1999-03-25 | ||
| PCT/US1999/010187 WO1999061444A2 (en) | 1998-05-26 | 1999-05-10 | Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002516327A true JP2002516327A (ja) | 2002-06-04 |
| JP2002516327A5 JP2002516327A5 (https=) | 2006-06-22 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000550849A Abandoned JP2002516327A (ja) | 1998-05-26 | 1999-05-10 | 細胞増殖の阻害剤としての二環式ピリミジンおよび二環式３，４−ジヒドロピリミジン |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US7501425B1 (https=) |
| EP (1) | EP1080092B1 (https=) |
| JP (1) | JP2002516327A (https=) |
| KR (1) | KR20010043829A (https=) |
| CN (1) | CN1138778C (https=) |
| AP (1) | AP2000001964A0 (https=) |
| AT (1) | ATE402177T1 (https=) |
| AU (1) | AU763839B2 (https=) |
| BG (1) | BG104960A (https=) |
| BR (1) | BR9911590A (https=) |
| CA (1) | CA2329703C (https=) |
| DE (1) | DE69939168D1 (https=) |
| EA (1) | EA003640B1 (https=) |
| EE (1) | EE200000706A (https=) |
| ES (1) | ES2310039T3 (https=) |
| GE (1) | GEP20033093B (https=) |
| HR (1) | HRP20000799A2 (https=) |
| HU (1) | HUP0102514A3 (https=) |
| ID (1) | ID27589A (https=) |
| IL (1) | IL139599A0 (https=) |
| IS (1) | IS5687A (https=) |
| NO (1) | NO20005928D0 (https=) |
| NZ (1) | NZ508268A (https=) |
| PL (1) | PL344248A1 (https=) |
| SK (1) | SK17532000A3 (https=) |
| TR (1) | TR200003429T2 (https=) |
| WO (1) | WO1999061444A2 (https=) |
| YU (1) | YU73300A (https=) |
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| JP2006526587A (ja) * | 2003-06-04 | 2006-11-24 | バイエル・クロツプサイエンス・アクチエンゲゼルシヤフト | トリアゾロピリミジン類 |
| JP2007500725A (ja) * | 2003-07-29 | 2007-01-18 | アイアールエム・リミテッド・ライアビリティ・カンパニー | プロテインキナーゼ阻害剤としての化合物および組成物 |
| JP2008509964A (ja) * | 2004-08-31 | 2008-04-03 | エフ．ホフマン−ラ ロシュ アーゲー | ７−アミノ−３−フェニル−ジヒドロピリミド［４，５−ｄ］ピリミジノンのアミド誘導体、これらの製造、及びプロテインキナーゼ阻害剤としての使用 |
| JP2008510690A (ja) * | 2004-08-31 | 2008-04-10 | エフ．ホフマン−ラ ロシュ アーゲー | ３−フェニル−ジヒドロピリミド［４，５−ｄ］ピリミジノンのアミド誘導体、これらの製造、及び医薬品としての使用 |
| WO2010098367A1 (en) * | 2009-02-25 | 2010-09-02 | Banyu Pharmaceutical Co.,Ltd. | Pyrimidopyrimidoindazole derivative |
| JP4812763B2 (ja) * | 2004-05-18 | 2011-11-09 | ライジェル ファーマシューティカルズ， インコーポレイテッド | シクロアルキル置換ピリミジンジアミン化合物およびそれらの用途 |
| JP5129812B2 (ja) * | 2007-06-15 | 2013-01-30 | Ｍｓｄ株式会社 | ビシクロアニリン誘導体 |
| JP2013519725A (ja) * | 2010-02-17 | 2013-05-30 | デバイオファーム エスエイ | 二環式化合物および二重ｃ−ＳＲＣ／ＪＡＫ阻害剤としてのそれらの使用 |
| JP2016518372A (ja) * | 2013-04-19 | 2016-06-23 | インサイト・コーポレイションＩｎｃｙｔｅ Ｃｏｒｐｏｒａｔｉｏｎ | Ｆｇｆｒ抑制剤としての二環式複素環 |
| KR20190015470A (ko) * | 2016-06-06 | 2019-02-13 | 상하이 알리스트 파마슈티컬 앤 메디컬 테크놀로지 코퍼레이션스 | 융합된 피리미디노피페리딘 유도체, 및 그의 제조 방법 및 용도 |
| JP2019527682A (ja) * | 2016-07-05 | 2019-10-03 | ザ ブロード インスティテュート, インコーポレーテッドThe Broad Institute, Inc. | 二環式尿素キナーゼインヒビターおよびそれらの使用 |
| US10611762B2 (en) | 2017-05-26 | 2020-04-07 | Incyte Corporation | Crystalline forms of a FGFR inhibitor and processes for preparing the same |
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| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
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| TR200003429T2 (tr) | 1998-05-26 | 2001-07-23 | Warner-Lambert Company | Hücresel çoğalma inhibitörleri olarak bisiklik pirimidinler ve bisiklik 3,4-dihidropirimidinler. |
| HK1041483B (zh) * | 1998-10-23 | 2004-12-24 | 霍夫曼-拉罗奇有限公司 | 雙環氮雜環 |
| AU776250B2 (en) | 1999-10-21 | 2004-09-02 | F. Hoffmann-La Roche Ag | Heteroalkylamino-substituted bicyclic nitrogen heterocycles as inhibitors of P38 protein kinase |
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| SK10572002A3 (sk) * | 2000-01-24 | 2003-10-07 | Warner-Lambert Company | 3-Aminochinazolín-2,4-diónové antibakteriálne činidlá |
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| CA2420286A1 (en) * | 2000-08-31 | 2002-03-07 | F. Hoffmann-La Roche Ag | 7-oxo pyridopyrimidines as inhibitors of a cellular proliferation |
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