HRP20000799A2 - Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation - Google Patents

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Publication number

HRP20000799A2

HRP20000799A2 HR20000799A HRP20000799A HRP20000799A2 HR P20000799 A2 HRP20000799 A2 HR P20000799A2 HR 20000799 A HR20000799 A HR 20000799A HR P20000799 A HRP20000799 A HR P20000799A HR P20000799 A2 HRP20000799 A2 HR P20000799A2

Authority

HR

Croatia

Prior art keywords

pyrimido

phenylamino

pyrimidin

dihydro

methyl

Prior art date

1998-05-26

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• -1 Bicyclic pyrimidines Chemical class 0.000 title claims description 106
• 239000003112 inhibitor Substances 0.000 title description 11
• 230000004663 cell proliferation Effects 0.000 title description 5
• 150000001875 compounds Chemical class 0.000 claims description 141
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 58
• 238000000034 method Methods 0.000 claims description 57
• HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 claims description 52
• 125000000217 alkyl group Chemical group 0.000 claims description 41
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 40
• 229910052757 nitrogen Inorganic materials 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 35
• 150000003839 salts Chemical class 0.000 claims description 28
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 25
• 229910052736 halogen Inorganic materials 0.000 claims description 23
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 23
• 229910052760 oxygen Inorganic materials 0.000 claims description 23
• 150000002367 halogens Chemical class 0.000 claims description 22
• 125000001072 heteroaryl group Chemical group 0.000 claims description 22
• 101100295741 Gallus gallus COR4 gene Proteins 0.000 claims description 21
• 206010028980 Neoplasm Diseases 0.000 claims description 21
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
• 125000003545 alkoxy group Chemical group 0.000 claims description 20
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 19
• 150000002466 imines Chemical group 0.000 claims description 18
• 229910052717 sulfur Inorganic materials 0.000 claims description 18
• 102000003903 Cyclin-dependent kinases Human genes 0.000 claims description 17
• 108090000266 Cyclin-dependent kinases Proteins 0.000 claims description 17
• 230000002401 inhibitory effect Effects 0.000 claims description 17
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 16
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 16
• 108091000080 Phosphotransferase Proteins 0.000 claims description 15
• 102000020233 phosphotransferase Human genes 0.000 claims description 15
• VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 claims description 15
• 150000003573 thiols Chemical class 0.000 claims description 15
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 14
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical class [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
• 201000011510 cancer Diseases 0.000 claims description 13
• 239000001301 oxygen Chemical class 0.000 claims description 13
• 230000002062 proliferating effect Effects 0.000 claims description 13
• 201000010099 disease Diseases 0.000 claims description 12
• 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 12
• 239000001257 hydrogen Substances 0.000 claims description 12
• 229910052739 hydrogen Inorganic materials 0.000 claims description 12
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 12
• 108050007372 Fibroblast Growth Factor Proteins 0.000 claims description 11
• 102000018233 Fibroblast Growth Factor Human genes 0.000 claims description 11
• 229940126864 fibroblast growth factor Drugs 0.000 claims description 11
• 125000005842 heteroatom Chemical group 0.000 claims description 11
• 125000004076 pyridyl group Chemical group 0.000 claims description 11
• 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 10
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 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
• 230000033115 angiogenesis Effects 0.000 claims description 10
• 125000004432 carbon atom Chemical group C* 0.000 claims description 10
• 101150073031 cdk2 gene Proteins 0.000 claims description 10
• 230000035755 proliferation Effects 0.000 claims description 10
• 208000037803 restenosis Diseases 0.000 claims description 10
• 201000001320 Atherosclerosis Diseases 0.000 claims description 9
• 101100005789 Caenorhabditis elegans cdk-4 gene Proteins 0.000 claims description 9
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims description 9
• 239000004202 carbamide Substances 0.000 claims description 9
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
• 208000035475 disorder Diseases 0.000 claims description 9
• 239000003102 growth factor Substances 0.000 claims description 9
• 150000002829 nitrogen Chemical class 0.000 claims description 9
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims description 8
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical class [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
• 125000000623 heterocyclic group Chemical group 0.000 claims description 8
• 150000002825 nitriles Chemical class 0.000 claims description 8
• 239000011593 sulfur Chemical class 0.000 claims description 8
• 125000004001 thioalkyl group Chemical group 0.000 claims description 8
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 7
• 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 7
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 7
• 241000124008 Mammalia Species 0.000 claims description 7
• 201000004681 Psoriasis Diseases 0.000 claims description 7
• 230000001404 mediated effect Effects 0.000 claims description 7
• 210000002464 muscle smooth vascular Anatomy 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
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 6
• JPOJBQLUJAIHHL-UHFFFAOYSA-N 1h-pyrimido[4,5-d]pyrimidin-2-one Chemical compound N1=CN=C2NC(=O)N=CC2=C1 JPOJBQLUJAIHHL-UHFFFAOYSA-N 0.000 claims description 6
• 150000002431 hydrogen Chemical class 0.000 claims description 6
• 102000037979 non-receptor tyrosine kinases Human genes 0.000 claims description 6
• 108091008046 non-receptor tyrosine kinases Proteins 0.000 claims description 6
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 5
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical class ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 claims description 5
• 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 4
• FXCWWKGXYURZGF-UHFFFAOYSA-N 8-methyl-2-[4-(4-methylpiperazin-1-yl)anilino]-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C(CNC(=O)N2C)C2=N1 FXCWWKGXYURZGF-UHFFFAOYSA-N 0.000 claims description 4
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 4
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 4
• 230000003993 interaction Effects 0.000 claims description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• NFKADCJUKLTGRB-UHFFFAOYSA-N 1-propan-2-yl-7-(4-pyrazol-1-ylanilino)pyrimido[4,5-d]pyrimidin-2-one Chemical compound N=1C=C2C=NC(=O)N(C(C)C)C2=NC=1NC(C=C1)=CC=C1N1C=CC=N1 NFKADCJUKLTGRB-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
• LSQGLPJPPZIBTL-UHFFFAOYSA-N 7-[4-(diethylamino)butylamino]-3-(3,5-dimethoxyphenyl)-1-ethyl-4h-pyrimido[4,5-d]pyrimidin-2-one Chemical compound O=C1N(CC)C2=NC(NCCCCN(CC)CC)=NC=C2CN1C1=CC(OC)=CC(OC)=C1 LSQGLPJPPZIBTL-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
• SRCVYIHSYUUCQT-UHFFFAOYSA-N 8-(3-bicyclo[2.2.1]heptanyl)-2-[4-(4-methylpiperazin-1-yl)anilino]-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C(CNC(=O)N2C3C4CCC(C4)C3)C2=N1 SRCVYIHSYUUCQT-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
• 206010039491 Sarcoma Diseases 0.000 claims description 3
• 206010057469 Vascular stenosis Diseases 0.000 claims description 3
• 230000002980 postoperative effect Effects 0.000 claims description 3
• 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
• CXCVAMWLZIFURV-UHFFFAOYSA-N 1-(3-bicyclo[2.2.1]heptanyl)-7-[4-[4-(3-morpholin-4-ylpropyl)piperidin-1-yl]anilino]pyrimido[4,5-d]pyrimidin-2-one Chemical compound N1=C2N(C3C4CCC(C4)C3)C(=O)N=CC2=CN=C1NC(C=C1)=CC=C1N(CC1)CCC1CCCN1CCOCC1 CXCVAMWLZIFURV-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
• WALFZDZPONVUIH-UHFFFAOYSA-N 1-(3-hydroxypropyl)-7-[4-(4-methylpiperazin-1-yl)anilino]pyrido[4,3-d]pyrimidin-2-one Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC(N=C1)=CC2=C1C=NC(=O)N2CCCO WALFZDZPONVUIH-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
• 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
• 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
• 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
• SEGPMNJSRKJLRF-UHFFFAOYSA-N 1-cyclopentyl-7-(4-fluoro-3-methylanilino)pyrimido[4,5-d]pyrimidin-2-one Chemical compound C1=C(F)C(C)=CC(NC=2N=C3N(C4CCCC4)C(=O)N=CC3=CN=2)=C1 SEGPMNJSRKJLRF-UHFFFAOYSA-N 0.000 claims description 2
• LYPJMMVRHFYBED-UHFFFAOYSA-N 1-cyclopentyl-7-(4-methylsulfonylanilino)pyrimido[4,5-d]pyrimidin-2-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1NC1=NC=C(C=NC(=O)N2C3CCCC3)C2=N1 LYPJMMVRHFYBED-UHFFFAOYSA-N 0.000 claims description 2
• CMPAWLHWVNKEHO-UHFFFAOYSA-N 1-cyclopentyl-7-(pyridin-4-ylamino)pyrimido[4,5-d]pyrimidin-2-one Chemical compound N1=C2N(C3CCCC3)C(=O)N=CC2=CN=C1NC1=CC=NC=C1 CMPAWLHWVNKEHO-UHFFFAOYSA-N 0.000 claims description 2
• MAFLMDDLVBFCJM-UHFFFAOYSA-N 1-cyclopentyl-7-[4-[4-(3-morpholin-4-ylpropyl)piperidin-1-yl]anilino]pyrimido[4,5-d]pyrimidin-2-one Chemical compound N1=C2N(C3CCCC3)C(=O)N=CC2=CN=C1NC(C=C1)=CC=C1N(CC1)CCC1CCCN1CCOCC1 MAFLMDDLVBFCJM-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
• MXEAYMDSLOTGOA-UHFFFAOYSA-N 1-hexa-2,4-dienyl-7-[4-(4-methylpiperazin-1-yl)anilino]pyrido[4,3-d]pyrimidin-2-one Chemical compound N=1C=C2C=NC(=O)N(CC=CC=CC)C2=CC=1NC(C=C1)=CC=C1N1CCN(C)CC1 MXEAYMDSLOTGOA-UHFFFAOYSA-N 0.000 claims description 2
• 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 2
• FAIRRWVQRAQPBG-UHFFFAOYSA-N 1-tert-butyl-3-[3-(2-chloro-3,5-dimethoxyphenyl)-7-[4-[2-(diethylamino)ethoxy]anilino]-4h-pyrimido[4,5-d]pyrimidin-2-yl]urea Chemical compound C1=CC(OCCN(CC)CC)=CC=C1NC1=NC=C(CN(C(NC(=O)NC(C)(C)C)=N2)C=3C(=C(OC)C=C(OC)C=3)Cl)C2=N1 FAIRRWVQRAQPBG-UHFFFAOYSA-N 0.000 claims description 2
• VPNHAJYZVQXPDL-UHFFFAOYSA-N 2-[4-(2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[3,4-c]pyrrol-5-yl)anilino]-8-cyclopentyl-8h-pyrido[4,3-d]pyrimidin-7-one Chemical compound O=C1N=CC2=CN=C(NC=3C=CC(=CC=3)N3CC4CNCC4C3)N=C2C1C1CCCC1 VPNHAJYZVQXPDL-UHFFFAOYSA-N 0.000 claims description 2
• UFSSFDMEEMIJIW-UHFFFAOYSA-N 2-[4-(3-aminopyrrolidin-1-yl)anilino]-8-propan-2-yl-8h-pyrido[4,3-d]pyrimidin-7-one Chemical compound N1=C2C(C(C)C)C(=O)N=CC2=CN=C1NC(C=C1)=CC=C1N1CCC(N)C1 UFSSFDMEEMIJIW-UHFFFAOYSA-N 0.000 claims description 2
• KQVTUIKOGACPKS-UHFFFAOYSA-N 2-[4-(4-acetylpiperazin-1-yl)anilino]-8-cyclopentyl-8h-pyrido[4,3-d]pyrimidin-7-one Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=NC(=O)C2C3CCCC3)C2=N1 KQVTUIKOGACPKS-UHFFFAOYSA-N 0.000 claims description 2
• SLSXXMZCLRYNCE-UHFFFAOYSA-N 2-[4-(4-methylpiperazin-1-yl)anilino]-8-propan-2-ylpyrimido[4,5-d]pyrimidine-5,7-dione Chemical compound N=1C=C2C(=O)NC(=O)N(C(C)C)C2=NC=1NC(C=C1)=CC=C1N1CCN(C)CC1 SLSXXMZCLRYNCE-UHFFFAOYSA-N 0.000 claims description 2
• CCECTNAHAIMUMV-UHFFFAOYSA-N 2-[4-[2-(diethylamino)ethoxy]anilino]-6-(3,5-dimethoxyphenyl)-5,8-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound C1=CC(OCCN(CC)CC)=CC=C1NC1=NC=C(CN(C(=O)N2)C=3C=C(OC)C=C(OC)C=3)C2=N1 CCECTNAHAIMUMV-UHFFFAOYSA-N 0.000 claims description 2
• DKTBRRPWLIMTOU-UHFFFAOYSA-N 2-[4-[2-(diethylamino)ethoxy]anilino]-8-propan-2-ylpyrimido[4,5-d]pyrimidine-5,7-dione Chemical compound C1=CC(OCCN(CC)CC)=CC=C1NC1=NC=C2C(=O)NC(=O)N(C(C)C)C2=N1 DKTBRRPWLIMTOU-UHFFFAOYSA-N 0.000 claims description 2
• NNXCBTRERGAZEA-UHFFFAOYSA-N 3-(2,6-dichloro-3-hydroxyphenyl)-7-[3-(hydroxymethyl)anilino]-1-methyl-4h-pyrimido[4,5-d]pyrimidin-2-one Chemical compound N1=C2N(C)C(=O)N(C=3C(=C(O)C=CC=3Cl)Cl)CC2=CN=C1NC1=CC=CC(CO)=C1 NNXCBTRERGAZEA-UHFFFAOYSA-N 0.000 claims description 2
• ZMJAWSDJCUMJJN-UHFFFAOYSA-N 3-(2,6-dichloro-3-hydroxyphenyl)-7-[4-[2-(ethylamino)ethoxy]anilino]-1-methyl-4h-pyrimido[4,5-d]pyrimidin-2-one Chemical compound C1=CC(OCCNCC)=CC=C1NC1=NC=C(CN(C(=O)N2C)C=3C(=C(O)C=CC=3Cl)Cl)C2=N1 ZMJAWSDJCUMJJN-UHFFFAOYSA-N 0.000 claims description 2
• DDHHWHJBJCYDFY-UHFFFAOYSA-N 3-(3,5-dimethoxyphenyl)-1-ethyl-7-(pyridin-4-ylamino)-4h-pyrido[4,3-d]pyrimidin-2-one Chemical compound C1=C2N(CC)C(=O)N(C=3C=C(OC)C=C(OC)C=3)CC2=CN=C1NC1=CC=NC=C1 DDHHWHJBJCYDFY-UHFFFAOYSA-N 0.000 claims description 2
• BKHNPXOUNMTMCY-UHFFFAOYSA-N 3-[[3-(2,6-dichlorophenyl)-1-methyl-2-oxo-4h-pyrimido[4,5-d]pyrimidin-7-yl]amino]benzoic acid Chemical compound N1=C2N(C)C(=O)N(C=3C(=CC=CC=3Cl)Cl)CC2=CN=C1NC1=CC=CC(C(O)=O)=C1 BKHNPXOUNMTMCY-UHFFFAOYSA-N 0.000 claims description 2
• ZGVAHFAZEXHQBU-UHFFFAOYSA-N 3-methyl-n-[2-[4-(2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)anilino]-5,8-dihydropyrimido[4,5-d]pyrimidin-7-yl]butanamide Chemical compound N=1C=C2CNC(NC(=O)CC(C)C)=NC2=NC=1NC(C=C1)=CC=C1N1CC2CN(C)CC2C1 ZGVAHFAZEXHQBU-UHFFFAOYSA-N 0.000 claims description 2
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