JP2003525295A5 - - Google Patents
Download PDFInfo
- Publication number
- 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
- Authority
- 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
Links
- 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
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US18641900P | 2000-03-02 | 2000-03-02 | |
| US60/186,419 | 2000-03-02 | ||
| 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 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2003525295A JP2003525295A (ja) | 2003-08-26 |
| JP2003525295A5 true JP2003525295A5 (enExample) | 2008-04-03 |
Family
ID=22684876
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001564176A Pending JP2003525295A (ja) | 2000-03-02 | 2001-03-02 | １，５−二置換−３，４−ジヒドロ−１ｈ−ピリミド［４，５−ｄ］ピリミジン−２−オン化合物およびｃｓｂｐ／ｐ３８キナーゼ介在疾患の治療におけるその使用 |
Country Status (25)
| Country | Link |
|---|---|
| EP (1) | EP1265900B1 (enExample) |
| JP (1) | JP2003525295A (enExample) |
| KR (1) | KR100806978B1 (enExample) |
| CN (1) | CN100482664C (enExample) |
| AR (2) | AR030053A1 (enExample) |
| AT (1) | ATE362473T1 (enExample) |
| AU (2) | AU3999201A (enExample) |
| BR (1) | BR0108715A (enExample) |
| CA (1) | CA2402092C (enExample) |
| CY (1) | CY1106816T1 (enExample) |
| CZ (1) | CZ20022933A3 (enExample) |
| DE (1) | DE60128457T2 (enExample) |
| DK (1) | DK1265900T3 (enExample) |
| ES (1) | ES2287107T3 (enExample) |
| HU (1) | HUP0204431A3 (enExample) |
| IL (3) | IL151426A0 (enExample) |
| MX (1) | MXPA02008588A (enExample) |
| MY (1) | MY141144A (enExample) |
| NO (1) | NO326409B1 (enExample) |
| NZ (1) | NZ520914A (enExample) |
| PL (1) | PL358280A1 (enExample) |
| PT (1) | PT1265900E (enExample) |
| TW (1) | TWI290926B (enExample) |
| WO (1) | WO2001064679A1 (enExample) |
| ZA (1) | ZA200207017B (enExample) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69939168D1 (de) | 1998-05-26 | 2008-09-04 | Warner Lambert Co | Bicyclische pyrimidine und bicyclische 3,4-dihydropyrimidine als inhibitoren der zellvermehrung |
| 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 |
| JP2003514900A (ja) | 1999-11-23 | 2003-04-22 | スミスクライン・ビーチャム・コーポレイション | ＣＳＢＰ／ｐ３８キナーゼ阻害剤としての３，４−ジヒドロ−（１Ｈ）−キナゾリン−２−オン化合物 |
| 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 |
| AU2002246855B2 (en) * | 2000-10-23 | 2005-12-22 | Smithkline Beecham Corporation | Novel compounds |
| JP2004521892A (ja) * | 2000-12-20 | 2004-07-22 | メルク エンド カムパニー インコーポレーテッド | （ハロ−ベンゾカルボニル）複素環縮合フェニル系ｐ３８キナーゼ阻害剤 |
| GB0124848D0 (en) * | 2001-10-16 | 2001-12-05 | Celltech R&D Ltd | Chemical compounds |
| CN100369898C (zh) | 2002-02-12 | 2008-02-20 | 史密丝克莱恩比彻姆公司 | 用作p38抑制剂的烟酰胺衍生物 |
| CN1324015C (zh) | 2002-02-13 | 2007-07-04 | 霍夫曼-拉罗奇有限公司 | 吡啶－和嘧啶－衍生物 |
| KR20040103972A (ko) * | 2002-04-19 | 2004-12-09 | 스미스클라인 비참 코포레이션 | 신규 화합물 |
| GB0214268D0 (en) * | 2002-06-20 | 2002-07-31 | Celltech R&D Ltd | Chemical compounds |
| US7196090B2 (en) | 2002-07-25 | 2007-03-27 | Warner-Lambert Company | Kinase inhibitors |
| 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 |
| EP1539121A4 (en) | 2002-08-29 | 2008-08-13 | Scios Inc | METHOD OF REQUESTING OSTEOGENESIS |
| US7129351B2 (en) | 2002-11-04 | 2006-10-31 | Hoffmann-La Roche Inc. | Pyrimido compounds having antiproliferative activity |
| US7384937B2 (en) | 2002-11-06 | 2008-06-10 | Bristol-Myers Squibb Co. | 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 |
| CA2521124A1 (en) | 2003-04-10 | 2004-10-21 | F. Hoffmann-La Roche Ag | Pyrimido compounds |
| US7244441B2 (en) | 2003-09-25 | 2007-07-17 | Scios, Inc. | Stents and intra-luminal prostheses containing map kinase inhibitors |
| JP2007517052A (ja) * | 2003-12-23 | 2007-06-28 | ノバルティス アクチエンゲゼルシャフト | 二環式ヘテロ環式ｐ−３８キナーゼ阻害剤 |
| 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 |
| WO2007147109A2 (en) * | 2006-06-16 | 2007-12-21 | Glaxo Group Limited | Novel compounds |
| EP2031965A4 (en) * | 2006-06-16 | 2010-06-30 | Glaxo Group Ltd | NEW COMPOUNDS |
| 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 |
| TWI647220B (zh) | 2013-03-15 | 2019-01-11 | 美商西建卡爾有限責任公司 | 雜芳基化合物及其用途 |
| MY181020A (en) | 2013-03-15 | 2020-12-16 | Sanofi Sa | Heteroaryl compounds and uses thereof |
| CN106831722B (zh) | 2013-10-16 | 2019-08-30 | 上海璎黎药业有限公司 | 稠合杂环化合物、其制备方法、药物组合物和用途 |
| MA38393B1 (fr) | 2014-03-13 | 2018-11-30 | Sanofi Sa | Composés hétéroaryle et utilisations associées |
| US20190060286A1 (en) | 2016-02-29 | 2019-02-28 | University Of Florida Research Foundation, Incorpo | Chemotherapeutic Methods |
| ES2927715T3 (es) | 2017-10-05 | 2022-11-10 | Fulcrum Therapeutics Inc | Inhibidores de la quinasa p38 reducen la expresión de dux4 y de los genes que le siguen para el tratamiento de la FSHD |
| CN118434722A (zh) | 2021-10-20 | 2024-08-02 | 英矽智能科技知识产权有限公司 | 甲硫氨酸腺苷转移酶2a(mat2a)抑制剂及其用途 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| DK0920429T3 (da) * | 1996-08-06 | 2003-05-12 | Pfizer | Substituerede pyrido- eller pyrimidoholdige, 6,6- eller 6,7-bicykliske derivater |
| DE69939168D1 (de) * | 1998-05-26 | 2008-09-04 | Warner Lambert Co | Bicyclische pyrimidine und bicyclische 3,4-dihydropyrimidine als inhibitoren der zellvermehrung |
| AU4429799A (en) * | 1998-06-12 | 1999-12-30 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
| PL347432A1 (en) * | 1998-10-23 | 2002-04-08 | Hoffmann La Roche | Bicyclic nitrogen heterocycles |
-
2001
- 2001-02-28 AR ARP010100940A patent/AR030053A1/es unknown
- 2001-02-28 MY MYPI20010900A patent/MY141144A/en unknown
- 2001-03-02 NZ NZ520914A patent/NZ520914A/en not_active IP Right Cessation
- 2001-03-02 KR KR1020027011408A patent/KR100806978B1/ko not_active Expired - Fee Related
- 2001-03-02 JP JP2001564176A patent/JP2003525295A/ja active Pending
- 2001-03-02 WO PCT/US2001/006688 patent/WO2001064679A1/en not_active Ceased
- 2001-03-02 CN CNB018076866A patent/CN100482664C/zh not_active Expired - Fee Related
- 2001-03-02 PT PT01914625T patent/PT1265900E/pt unknown
- 2001-03-02 AU AU3999201A patent/AU3999201A/xx active Pending
- 2001-03-02 HU HU0204431A patent/HUP0204431A3/hu unknown
- 2001-03-02 DE DE60128457T patent/DE60128457T2/de not_active Expired - Lifetime
- 2001-03-02 EP EP01914625A patent/EP1265900B1/en not_active Expired - Lifetime
- 2001-03-02 TW TW090104783A patent/TWI290926B/zh not_active IP Right Cessation
- 2001-03-02 IL IL15142601A patent/IL151426A0/xx active IP Right Grant
- 2001-03-02 BR BR0108715-0A patent/BR0108715A/pt not_active Application Discontinuation
- 2001-03-02 MX MXPA02008588A patent/MXPA02008588A/es active IP Right Grant
- 2001-03-02 ES ES01914625T patent/ES2287107T3/es not_active Expired - Lifetime
- 2001-03-02 CZ CZ20022933A patent/CZ20022933A3/cs unknown
- 2001-03-02 CA CA2402092A patent/CA2402092C/en not_active Expired - Fee Related
- 2001-03-02 AU AU2001239992A patent/AU2001239992B2/en not_active Ceased
- 2001-03-02 DK DK01914625T patent/DK1265900T3/da active
- 2001-03-02 AT AT01914625T patent/ATE362473T1/de active
- 2001-03-02 PL PL01358280A patent/PL358280A1/xx not_active Application Discontinuation
-
2002
- 2002-08-22 IL IL151426A patent/IL151426A/en not_active IP Right Cessation
- 2002-08-30 NO NO20024134A patent/NO326409B1/no not_active IP Right Cessation
- 2002-09-02 ZA ZA200207017A patent/ZA200207017B/en unknown
-
2003
- 2003-05-07 AR ARP030101602A patent/AR040075A2/es unknown
-
2007
- 2007-08-13 CY CY20071101080T patent/CY1106816T1/el unknown
-
2008
- 2008-02-28 IL IL189865A patent/IL189865A0/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2402092A1 (en) | 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 | |
| AU655798B2 (en) | 2,4-diaminoquinazolines derivatives for enhancing antitumor activity | |
| DK2346837T3 (en) | Methods for preparing quinazolinone derivatives | |
| US8962644B2 (en) | Benzoimidazol-2-yl pyrimidines and pyrazines as modulators of the histamine H4 receptor | |
| US11014895B2 (en) | Heterocyclic urea compound, and drug composition and application thereof | |
| US10399978B2 (en) | Imidazopyridine thioglycolic acid derivatives as potent inhibitors of human urate transporter 1 | |
| US20050222152A1 (en) | New use of pyrimidine - or triazine - 2 carbonitiles for treating diseases associated with cysteine prostease activity and novel pyrimidine-2-carbonitile derivatives | |
| NZ526958A (en) | Novel 2-alkyl substituted imidazole compounds | |
| JP6804516B2 (ja) | 変異イソクエン酸デヒドロゲナーゼｉｄｈ１ ｒ１３２ｈの阻害剤 | |
| CN106518924A (zh) | 用于治疗 nk‑1 受体相关疾病的取代的 4‑苯基吡啶 | |
| US20030100558A1 (en) | Triazole compounds useful in treating diseases associated with unwanted cytokine activity | |
| RU2006134020A (ru) | Конденсированные производные пиразола | |
| JP2006517976A5 (enExample) | ||
| JP5129138B2 (ja) | 新規なベンジル（ピリジルメチル）アミン構造を有するピリミジン化合物及びこれを含有する医薬 | |
| JP2009515984A5 (enExample) | ||
| JP4272056B2 (ja) | アリールピペラジンに連結したテトラヒドロインドロン及びプリン誘導体 | |
| WO2004076441A1 (ja) | 多酸性塩基化合物の酸付加塩の製造方法 | |
| CN107033149B (zh) | 一种dpp-4酶抑制剂及其制备和应用 | |
| WO2025106780A1 (en) | Rxfp1 receptor agonists | |
| US6770638B2 (en) | Tetrahydroindolone and purine derivatives linked to arylpiperazines | |
| RU94040854A (ru) | Триазолопиримидиновые производные как антагонисты рецепторов ангиотензина 11, способ их получения, фармацевтическая композиция | |
| JP4402959B2 (ja) | 縮合二環式ピリミジン誘導体 | |
| AU2023389998A1 (en) | Process for making antibody-drug conjugates | |
| JP2007520536A5 (enExample) | ||
| JPH06509353A (ja) | フリルチアゾールおよびそのｈ２−受容体拮抗剤および抗菌剤としての用途 |