JP2003525295A5 - - Google Patents
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- JP2003525295A5 JP2003525295A5 JP2001564176A JP2001564176A JP2003525295A5 JP 2003525295 A5 JP2003525295 A5 JP 2003525295A5 JP 2001564176 A JP2001564176 A JP 2001564176A JP 2001564176 A JP2001564176 A JP 2001564176A JP 2003525295 A5 JP2003525295 A5 JP 2003525295A5
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- JP
- Japan
- Prior art keywords
- alkyl
- optionally substituted
- dihydro
- pyrimido
- aryl
- 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.)
- Pending
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- 125000000217 alkyl group Chemical group 0.000 description 92
- 150000001875 compounds Chemical class 0.000 description 63
- 125000001072 heteroaryl group Chemical group 0.000 description 36
- 229910052739 hydrogen Inorganic materials 0.000 description 34
- 239000001257 hydrogen Substances 0.000 description 34
- -1 NR c Chemical group 0.000 description 33
- 125000003118 aryl group Chemical group 0.000 description 33
- 125000000623 heterocyclic group Chemical group 0.000 description 31
- 125000003107 substituted aryl group Chemical group 0.000 description 24
- 150000002431 hydrogen Chemical class 0.000 description 21
- 238000000034 method Methods 0.000 description 18
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 14
- 229910052760 oxygen Inorganic materials 0.000 description 14
- 239000001301 oxygen Substances 0.000 description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 13
- 206010040070 Septic Shock Diseases 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 11
- 229910052717 sulfur Inorganic materials 0.000 description 11
- 239000011593 sulfur Substances 0.000 description 11
- 229910052736 halogen Inorganic materials 0.000 description 10
- 150000002367 halogens Chemical class 0.000 description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical class C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- 206010012689 Diabetic retinopathy Diseases 0.000 description 8
- 201000005569 Gout Diseases 0.000 description 8
- 108010084680 Heterogeneous-Nuclear Ribonucleoprotein K Proteins 0.000 description 8
- 241000124008 Mammalia Species 0.000 description 8
- 102100023482 Mitogen-activated protein kinase 14 Human genes 0.000 description 8
- 206010035664 Pneumonia Diseases 0.000 description 8
- 206010040047 Sepsis Diseases 0.000 description 8
- 208000002780 macular degeneration Diseases 0.000 description 8
- 230000001404 mediated effect Effects 0.000 description 8
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 8
- 125000003545 alkoxy group Chemical group 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical class C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 125000001188 haloalkyl group Chemical group 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 4
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 4
- 206010007559 Cardiac failure congestive Diseases 0.000 description 4
- 206010063094 Cerebral malaria Diseases 0.000 description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 4
- 208000018652 Closed Head injury Diseases 0.000 description 4
- 206010009900 Colitis ulcerative Diseases 0.000 description 4
- 206010010741 Conjunctivitis Diseases 0.000 description 4
- 208000011231 Crohn disease Diseases 0.000 description 4
- 201000004624 Dermatitis Diseases 0.000 description 4
- 206010012442 Dermatitis contact Diseases 0.000 description 4
- 206010014824 Endotoxic shock Diseases 0.000 description 4
- 206010018364 Glomerulonephritis Diseases 0.000 description 4
- 206010018634 Gouty Arthritis Diseases 0.000 description 4
- 206010019280 Heart failures Diseases 0.000 description 4
- 208000016988 Hemorrhagic Stroke Diseases 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 4
- 208000032382 Ischaemic stroke Diseases 0.000 description 4
- 201000009906 Meningitis Diseases 0.000 description 4
- 206010027476 Metastases Diseases 0.000 description 4
- 206010028289 Muscle atrophy Diseases 0.000 description 4
- 208000001132 Osteoporosis Diseases 0.000 description 4
- 201000004681 Psoriasis Diseases 0.000 description 4
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 4
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 4
- 208000033464 Reiter syndrome Diseases 0.000 description 4
- 206010063837 Reperfusion injury Diseases 0.000 description 4
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 4
- 201000010001 Silicosis Diseases 0.000 description 4
- 206010042496 Sunburn Diseases 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 4
- 206010044248 Toxic shock syndrome Diseases 0.000 description 4
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 4
- 206010048873 Traumatic arthritis Diseases 0.000 description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 description 4
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 4
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 4
- 230000002491 angiogenic effect Effects 0.000 description 4
- 230000002917 arthritic effect Effects 0.000 description 4
- 206010003246 arthritis Diseases 0.000 description 4
- 208000006673 asthma Diseases 0.000 description 4
- 208000010668 atopic eczema Diseases 0.000 description 4
- 208000019664 bone resorption disease Diseases 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 208000020832 chronic kidney disease Diseases 0.000 description 4
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 4
- 208000010247 contact dermatitis Diseases 0.000 description 4
- 210000004351 coronary vessel Anatomy 0.000 description 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 208000024908 graft versus host disease Diseases 0.000 description 4
- 210000002216 heart Anatomy 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 206010022000 influenza Diseases 0.000 description 4
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 4
- 230000000302 ischemic effect Effects 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- 230000004770 neurodegeneration Effects 0.000 description 4
- 208000015122 neurodegenerative disease Diseases 0.000 description 4
- 201000008482 osteoarthritis Diseases 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 201000003651 pulmonary sarcoidosis Diseases 0.000 description 4
- 208000002574 reactive arthritis Diseases 0.000 description 4
- 208000037803 restenosis Diseases 0.000 description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 description 4
- 201000005404 rubella Diseases 0.000 description 4
- 230000036303 septic shock Effects 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 201000004595 synovitis Diseases 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- 125000003341 7 membered heterocyclic group Chemical group 0.000 description 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical class C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 150000002460 imidazoles Chemical class 0.000 description 3
- XFIVQPQXMLYMEL-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-(2-pyridin-3-ylethylamino)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound CC1=CC(F)=CC=C1C1=NC(NCCC=2C=NC=CC=2)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F XFIVQPQXMLYMEL-UHFFFAOYSA-N 0.000 description 2
- SJDADHVFQGGIIK-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-(4-methylpiperazin-1-yl)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound C1CN(C)CCN1C(N=C1C=2C(=CC(F)=CC=2)C)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F SJDADHVFQGGIIK-UHFFFAOYSA-N 0.000 description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 2
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 2
- GFPULOWPXJKUAA-UHFFFAOYSA-N 1-[8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-7-oxo-5,6-dihydropyrimido[4,5-d]pyrimidin-2-yl]piperidine-4-carboxylic acid Chemical compound CC1=CC(F)=CC=C1C1=NC(N2CCC(CC2)C(O)=O)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F GFPULOWPXJKUAA-UHFFFAOYSA-N 0.000 description 1
- ITDATIHWOGJRRY-UHFFFAOYSA-N 1-amino-3,4-dihydropyrimido[4,5-d]pyrimidin-2-one ethanol Chemical compound NN1C(NCC=2C1=NC=NC2)=O.CCO ITDATIHWOGJRRY-UHFFFAOYSA-N 0.000 description 1
- ITCXGNOGLOWIDP-UHFFFAOYSA-N 2-[2-(diethylamino)ethylamino]-8-(2,6-difluorophenyl)-4-(2-methylphenyl)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(NCCN(CC)CC)=NC=2N(C=3C(=CC=CC=3F)F)C(=O)NCC=2C=1C1=CC=CC=C1C ITCXGNOGLOWIDP-UHFFFAOYSA-N 0.000 description 1
- ZMIKRTDSJYSRIQ-UHFFFAOYSA-N 2-[2-[bis(2-hydroxyethyl)amino]ethoxy]-8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound CC1=CC(F)=CC=C1C1=NC(OCCN(CCO)CCO)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F ZMIKRTDSJYSRIQ-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- NHWQNBZGHWTZTF-UHFFFAOYSA-N 2-methoxy-4,8-diphenyl-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(OC)=NC=2N(C=3C=CC=CC=3)C(=O)NCC=2C=1C1=CC=CC=C1 NHWQNBZGHWTZTF-UHFFFAOYSA-N 0.000 description 1
- QPZMKCAFTCXOLA-UHFFFAOYSA-N 2-methylsulfanyl-4,8-diphenyl-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(SC)=NC=2N(C=3C=CC=CC=3)C(=O)NCC=2C=1C1=CC=CC=C1 QPZMKCAFTCXOLA-UHFFFAOYSA-N 0.000 description 1
- JVOOMMOBLOIUCK-UHFFFAOYSA-N 2-methylsulfanyl-4-phenyl-8-(1-phenylethyl)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound O=C1NCC=2C(C=3C=CC=CC=3)=NC(SC)=NC=2N1C(C)C1=CC=CC=C1 JVOOMMOBLOIUCK-UHFFFAOYSA-N 0.000 description 1
- POIUUYBLAPDZRL-CQSZACIVSA-N 4-(4-fluoro-2-methylphenyl)-2-methylsulfanyl-8-[(1r)-1-phenylethyl]-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound C1([C@@H](C)N2C=3N=C(N=C(C=3CNC2=O)C=2C(=CC(F)=CC=2)C)SC)=CC=CC=C1 POIUUYBLAPDZRL-CQSZACIVSA-N 0.000 description 1
- POIUUYBLAPDZRL-AWEZNQCLSA-N 4-(4-fluoro-2-methylphenyl)-2-methylsulfanyl-8-[(1s)-1-phenylethyl]-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound C1([C@H](C)N2C=3N=C(N=C(C=3CNC2=O)C=2C(=CC(F)=CC=2)C)SC)=CC=CC=C1 POIUUYBLAPDZRL-AWEZNQCLSA-N 0.000 description 1
- VTAGMHSMSZFMCO-UHFFFAOYSA-N 5-fluoro-2-[1-methyl-2-(2-methylphenyl)piperidin-4-yl]oxy-6,8-dihydro-5H-pyrimido[4,5-d]pyrimidin-7-one Chemical compound FC1NC(NC2=NC(=NC=C21)OC1CC(N(CC1)C)C1=C(C=CC=C1)C)=O VTAGMHSMSZFMCO-UHFFFAOYSA-N 0.000 description 1
- UXTBSKJWTIWZJC-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-2-(2,3-dihydroxypropylamino)-4-(4-fluoro-2-methylphenyl)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound CC1=CC(F)=CC=C1C1=NC(NCC(O)CO)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F UXTBSKJWTIWZJC-UHFFFAOYSA-N 0.000 description 1
- KKIFZUMHCDKAOR-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-2-[(1,3-dihydroxy-2-methylpropan-2-yl)amino]-4-(4-fluoro-2-methylphenyl)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound CC1=CC(F)=CC=C1C1=NC(NC(C)(CO)CO)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F KKIFZUMHCDKAOR-UHFFFAOYSA-N 0.000 description 1
- FWIQAZGOXKXCIO-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-2-methoxy-4-phenyl-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(OC)=NC=2N(C=3C(=CC=CC=3F)F)C(=O)NCC=2C=1C1=CC=CC=C1 FWIQAZGOXKXCIO-UHFFFAOYSA-N 0.000 description 1
- ZRQQTBJJAHYZCN-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-2-methylsulfanyl-4-phenyl-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(SC)=NC=2N(C=3C(=CC=CC=3F)F)C(=O)NCC=2C=1C1=CC=CC=C1 ZRQQTBJJAHYZCN-UHFFFAOYSA-N 0.000 description 1
- BQVQXFNBKINDHJ-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(2-methylphenyl)-2-methylsulfanyl-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(SC)=NC=2N(C=3C(=CC=CC=3F)F)C(=O)NCC=2C=1C1=CC=CC=C1C BQVQXFNBKINDHJ-UHFFFAOYSA-N 0.000 description 1
- NFCBJEPHFJANDG-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-(2-hydroxyethylamino)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound CC1=CC(F)=CC=C1C1=NC(NCCO)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F NFCBJEPHFJANDG-UHFFFAOYSA-N 0.000 description 1
- IUSUIUXWQUDOPR-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-(2-morpholin-4-ylethylamino)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound CC1=CC(F)=CC=C1C1=NC(NCCN2CCOCC2)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F IUSUIUXWQUDOPR-UHFFFAOYSA-N 0.000 description 1
- RBKUFYXURQWVHJ-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-(2-piperidin-1-ylethylamino)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound CC1=CC(F)=CC=C1C1=NC(NCCN2CCCCC2)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F RBKUFYXURQWVHJ-UHFFFAOYSA-N 0.000 description 1
- HKPXJUXWLNGMFC-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-(2-pyrrolidin-1-ylethylamino)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound CC1=CC(F)=CC=C1C1=NC(NCCN2CCCC2)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F HKPXJUXWLNGMFC-UHFFFAOYSA-N 0.000 description 1
- BMVPALGMLXXMPG-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-(4-hydroxypiperidin-1-yl)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound CC1=CC(F)=CC=C1C1=NC(N2CCC(O)CC2)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F BMVPALGMLXXMPG-UHFFFAOYSA-N 0.000 description 1
- CGRTXKHCITVACI-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-[(1-hydroxy-2-methylpropan-2-yl)amino]-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound CC1=CC(F)=CC=C1C1=NC(NC(C)(C)CO)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F CGRTXKHCITVACI-UHFFFAOYSA-N 0.000 description 1
- OWBLWOFCPKNBSN-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-[(1-methylpiperidin-4-yl)amino]-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound C1CN(C)CCC1NC(N=C1C=2C(=CC(F)=CC=2)C)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F OWBLWOFCPKNBSN-UHFFFAOYSA-N 0.000 description 1
- BRONJFZGPOXZGW-GFCCVEGCSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-[[(2r)-1-hydroxypropan-2-yl]amino]-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(N[C@@H](CO)C)=NC=2N(C=3C(=CC=CC=3F)F)C(=O)NCC=2C=1C1=CC=C(F)C=C1C BRONJFZGPOXZGW-GFCCVEGCSA-N 0.000 description 1
- BRONJFZGPOXZGW-LBPRGKRZSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-[[(2s)-1-hydroxypropan-2-yl]amino]-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(N[C@H](CO)C)=NC=2N(C=3C(=CC=CC=3F)F)C(=O)NCC=2C=1C1=CC=C(F)C=C1C BRONJFZGPOXZGW-LBPRGKRZSA-N 0.000 description 1
- RYLOGURSYLZAJG-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-[methyl(1,1,2-trihydroxyethyl)amino]-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(N(C)C(O)(O)CO)=NC=2N(C=3C(=CC=CC=3F)F)C(=O)NCC=2C=1C1=CC=C(F)C=C1C RYLOGURSYLZAJG-UHFFFAOYSA-N 0.000 description 1
- DQJMEYBIBKRMNE-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-methylsulfanyl-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(SC)=NC=2N(C=3C(=CC=CC=3F)F)C(=O)NCC=2C=1C1=CC=C(F)C=C1C DQJMEYBIBKRMNE-UHFFFAOYSA-N 0.000 description 1
- OWJIMCIWDXHGMZ-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-methylsulfonyl-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound CC1=CC(F)=CC=C1C1=NC(S(C)(=O)=O)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F OWJIMCIWDXHGMZ-UHFFFAOYSA-N 0.000 description 1
- UKDRKTYBKGGGFY-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluorophenyl)-2-methylsulfanyl-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(SC)=NC=2N(C=3C(=CC=CC=3F)F)C(=O)NCC=2C=1C1=CC=C(F)C=C1 UKDRKTYBKGGGFY-UHFFFAOYSA-N 0.000 description 1
- QNAFKGWWCNUNJJ-UHFFFAOYSA-N C12=NC(OCC)=NC=C2CNC(=O)N1C1=CC=C(F)C=C1C Chemical compound C12=NC(OCC)=NC=C2CNC(=O)N1C1=CC=C(F)C=C1C QNAFKGWWCNUNJJ-UHFFFAOYSA-N 0.000 description 1
- BFXAYXBWKHQXAB-UHFFFAOYSA-N C1CN(CCC1CO)N2C3=NC=NC=C3CNC2=O Chemical compound C1CN(CCC1CO)N2C3=NC=NC=C3CNC2=O BFXAYXBWKHQXAB-UHFFFAOYSA-N 0.000 description 1
- JZZKJWPYWONGMJ-UHFFFAOYSA-N CC1=CC(F)=CC=C1N1C2=NC(OCCO)=NC=C2CNC1=O Chemical compound CC1=CC(F)=CC=C1N1C2=NC(OCCO)=NC=C2CNC1=O JZZKJWPYWONGMJ-UHFFFAOYSA-N 0.000 description 1
- HJRZJLXRMCLQIU-UHFFFAOYSA-N CCN(CC)CCNN(C1=NC=NC=C1CN1)C1=O Chemical compound CCN(CC)CCNN(C1=NC=NC=C1CN1)C1=O HJRZJLXRMCLQIU-UHFFFAOYSA-N 0.000 description 1
- HSGBJJOLDDAAAC-UHFFFAOYSA-N CN1C=CN=C1N1C2=NC=NC=C2CNC1=O Chemical compound CN1C=CN=C1N1C2=NC=NC=C2CNC1=O HSGBJJOLDDAAAC-UHFFFAOYSA-N 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- VBPRDTNZCVKPNV-UHFFFAOYSA-N ethyl 1-[8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-7-oxo-5,6-dihydropyrimido[4,5-d]pyrimidin-2-yl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C(N=C1C=2C(=CC(F)=CC=2)C)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F VBPRDTNZCVKPNV-UHFFFAOYSA-N 0.000 description 1
- 125000005343 heterocyclic alkyl group Chemical group 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
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| PCT/US2001/006688 WO2001064679A1 (en) | 2000-03-02 | 2001-03-02 | 1,5-disubstituted-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one compounds and their use in treating csbp/p38 kinase mediated diseases |
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Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
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| ES2310039T3 (es) | 1998-05-26 | 2008-12-16 | Warner-Lambert Company Llc | Pirimidinas biciclicas y 3,4-dihidropirimidinas biciclicas como inhibidores de la proliferacion celular. |
| US6858617B2 (en) | 1998-05-26 | 2005-02-22 | Smithkline Beecham Corporation | Substituted imidazole compounds |
| DE60023025T2 (de) | 1999-11-23 | 2006-07-13 | Smithkline Beecham Corp. | 3,4-dihydro-(1h)chinazolin-2-on-verbindungen als csbp/p39-kinase-inhibitoren |
| WO2001038314A1 (en) | 1999-11-23 | 2001-05-31 | Smithkline Beecham Corporation | 3,4-dihydro-(1h)quinazolin-2-one compounds as csbp/p38 kinase inhibitors |
| ES2230171T3 (es) | 1999-11-23 | 2005-05-01 | Smithkline Beecham Corporation | Compuestos 3,4-dihidro-(1h)quinazolin-2-ona como inhibidores de csbp/p38 quinasa. |
| US7235551B2 (en) | 2000-03-02 | 2007-06-26 | Smithkline Beecham Corporation | 1,5-disubstituted-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one compounds and their use in treating csbp/p38 kinase mediated diseases |
| EP2404603A1 (en) * | 2000-10-23 | 2012-01-11 | Glaxosmithkline LLC | Novel trisubstituted-8H-pyrido[2,3-d]pyrimidin-7-one compounds for the treatment of CSBP/p38 kinase mediated diseases |
| EP1345603A4 (en) | 2000-12-20 | 2004-09-08 | Merck & Co Inc | (HALO-BENZO-CARBONYL) HETEROCYCLO-CONDENSED PHENYL-P38-KINASE INHIBITING AGENTS |
| GB0124848D0 (en) * | 2001-10-16 | 2001-12-05 | Celltech R&D Ltd | Chemical compounds |
| ATE375980T1 (de) | 2002-02-12 | 2007-11-15 | Smithkline Beecham Corp | Nicotinamide und deren verwendung als p38 inhibitoren |
| BR0307665A (pt) | 2002-02-13 | 2005-01-04 | Hoffmann La Roche | Compostos, processo para a sua manufatura, composições farmacêuticas que compreendem os mesmos, método para o tratamento e/ou profilaxia de enfermidades associadas com dpp iv e utilização dos compostos |
| US7629350B2 (en) * | 2002-04-19 | 2009-12-08 | Smithkline Beecham Corporation | Compounds |
| GB0214268D0 (en) * | 2002-06-20 | 2002-07-31 | Celltech R&D Ltd | Chemical compounds |
| PA8577501A1 (es) | 2002-07-25 | 2004-02-07 | Warner Lambert Co | Inhibidores de quinasas |
| GB0218800D0 (en) * | 2002-08-13 | 2002-09-18 | Celltech R&D Ltd | Chemical compounds |
| US7084270B2 (en) * | 2002-08-14 | 2006-08-01 | Hoffman-La Roche Inc. | Pyrimido compounds having antiproliferative activity |
| US7268139B2 (en) | 2002-08-29 | 2007-09-11 | Scios, Inc. | Methods of promoting osteogenesis |
| US7129351B2 (en) | 2002-11-04 | 2006-10-31 | Hoffmann-La Roche Inc. | Pyrimido compounds having antiproliferative activity |
| WO2004043367A2 (en) | 2002-11-06 | 2004-05-27 | Bristol-Myers Squibb Company | Fused heterocyclic compounds and use thereof |
| US7098332B2 (en) | 2002-12-20 | 2006-08-29 | Hoffmann-La Roche Inc. | 5,8-Dihydro-6H-pyrido[2,3-d]pyrimidin-7-ones |
| KR100864393B1 (ko) | 2003-04-10 | 2008-10-20 | 에프. 호프만-라 로슈 아게 | 피리미도 화합물 |
| US7244441B2 (en) | 2003-09-25 | 2007-07-17 | Scios, Inc. | Stents and intra-luminal prostheses containing map kinase inhibitors |
| US7569571B2 (en) * | 2003-12-23 | 2009-08-04 | Novartis Ag | Substituted pyrazolo [3,4-d]pyrimidines as cytokine modulators |
| US7767687B2 (en) | 2004-12-13 | 2010-08-03 | Biogen Idec Ma Inc. | Pyrido pyrimidinones, dihydro pyrimido pyrimidinones and pteridinones useful as RAF kinase inhibitors |
| EP1676574A3 (en) | 2004-12-30 | 2006-07-26 | Johnson & Johnson Vision Care, Inc. | Methods for promoting survival of transplanted tissues and cells |
| JP5201817B2 (ja) * | 2005-10-28 | 2013-06-05 | 大塚製薬株式会社 | 医薬組成物 |
| JP2009542818A (ja) * | 2006-06-16 | 2009-12-03 | グラクソ グループ リミテッド | 新規化合物 |
| JP2009542817A (ja) * | 2006-06-16 | 2009-12-03 | グラクソ グループ リミテッド | 新規化合物 |
| KR101040394B1 (ko) * | 2010-05-18 | 2011-06-09 | (주)이성산업 | 역화 방지 기능을 갖는 야외용 가스 히터 |
| CN102816162B (zh) * | 2011-06-10 | 2016-04-27 | 中国科学院广州生物医药与健康研究院 | 嘧啶并嘧啶酮类化合物及其药用组合物和应用 |
| NZ711376A (en) | 2013-03-15 | 2020-01-31 | Sanofi Sa | Heteroaryl compounds and uses thereof |
| US9321786B2 (en) | 2013-03-15 | 2016-04-26 | Celgene Avilomics Research, Inc. | Heteroaryl compounds and uses thereof |
| AU2014228746B2 (en) | 2013-03-15 | 2018-08-30 | Celgene Car Llc | Heteroaryl compounds and uses thereof |
| JP6139789B2 (ja) | 2013-10-16 | 2017-05-31 | シャンハイ インリ ファーマシューティカル カンパニー リミティド | 縮合複素環化合物、その調製方法、医薬組成物及びその使用 |
| WO2017151409A1 (en) | 2016-02-29 | 2017-09-08 | University Of Florida Research Foundation, Incorporated | Chemotherapeutic methods |
| US10342786B2 (en) | 2017-10-05 | 2019-07-09 | Fulcrum Therapeutics, Inc. | P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD |
| CA3127373A1 (en) | 2017-10-05 | 2019-04-11 | Fulcrum Therapeutics, Inc. | P38 kinase inhibitors reduce dux4 and downstream gene expression for the treatment of fshd |
| WO2023066283A1 (en) | 2021-10-20 | 2023-04-27 | Insilico Medicine Ip Limited | Methionine adenosyltransferase 2a (mat2a) inhibitors and uses thereof |
Family Cites Families (5)
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| JPS60226882A (ja) * | 1984-04-24 | 1985-11-12 | Nippon Zoki Pharmaceut Co Ltd | 新規ピリミドピリミジン誘導体 |
| EA003188B1 (ru) * | 1996-08-06 | 2003-02-27 | Пфайзер Инк | Замещенные пиридо- или пиримидосодержащие 6,6- или 6,7-бициклические производные |
| ES2310039T3 (es) * | 1998-05-26 | 2008-12-16 | Warner-Lambert Company Llc | Pirimidinas biciclicas y 3,4-dihidropirimidinas biciclicas como inhibidores de la proliferacion celular. |
| EP1086085A1 (en) * | 1998-06-12 | 2001-03-28 | Vertex Pharmaceuticals Incorporated | INHIBITORS OF p38 |
| NZ510760A (en) * | 1998-10-23 | 2003-08-29 | F | Bicyclic nitrogen heterocycles |
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- 2001-03-02 WO PCT/US2001/006688 patent/WO2001064679A1/en not_active Ceased
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