JP2002544262A - 有用な抗凝血剤としての置換多環式アリールおよびヘテロアリールピリミジノン - Google Patents
有用な抗凝血剤としての置換多環式アリールおよびヘテロアリールピリミジノンInfo
- Publication number
- JP2002544262A JP2002544262A JP2000618249A JP2000618249A JP2002544262A JP 2002544262 A JP2002544262 A JP 2002544262A JP 2000618249 A JP2000618249 A JP 2000618249A JP 2000618249 A JP2000618249 A JP 2000618249A JP 2002544262 A JP2002544262 A JP 2002544262A
- Authority
- JP
- Japan
- Prior art keywords
- group
- amino
- hydride
- carbon
- hydroxy
- 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
- -1 heteroaryl pyrimidinones Chemical class 0.000 title claims abstract description 1419
- 239000003146 anticoagulant agent Substances 0.000 title abstract description 7
- 229940127219 anticoagulant drug Drugs 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 62
- 150000003839 salts Chemical class 0.000 claims abstract description 49
- 238000000034 method Methods 0.000 claims abstract description 17
- 239000000203 mixture Substances 0.000 claims abstract description 13
- 230000001732 thrombotic effect Effects 0.000 claims abstract description 7
- 238000011282 treatment Methods 0.000 claims abstract description 7
- 230000002265 prevention Effects 0.000 claims abstract description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 537
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 387
- 150000004678 hydrides Chemical class 0.000 claims description 327
- 125000000217 alkyl group Chemical group 0.000 claims description 225
- 229910052757 nitrogen Inorganic materials 0.000 claims description 214
- 229910052760 oxygen Inorganic materials 0.000 claims description 191
- 229910052717 sulfur Inorganic materials 0.000 claims description 181
- 125000001188 haloalkyl group Chemical group 0.000 claims description 152
- 125000004429 atom Chemical group 0.000 claims description 151
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 145
- 125000005843 halogen group Chemical group 0.000 claims description 140
- 125000003282 alkyl amino group Chemical group 0.000 claims description 137
- 125000003545 alkoxy group Chemical group 0.000 claims description 121
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 117
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 101
- 125000004414 alkyl thio group Chemical group 0.000 claims description 80
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 72
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 64
- 125000000033 alkoxyamino group Chemical group 0.000 claims description 57
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 56
- 125000000623 heterocyclic group Chemical group 0.000 claims description 52
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 52
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 51
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 45
- 125000004076 pyridyl group Chemical group 0.000 claims description 44
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 41
- 125000001072 heteroaryl group Chemical group 0.000 claims description 41
- 125000003118 aryl group Chemical group 0.000 claims description 39
- 125000003342 alkenyl group Chemical group 0.000 claims description 38
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 37
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 35
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 35
- 125000004995 haloalkylthio group Chemical group 0.000 claims description 35
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 34
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 31
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 31
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 30
- 125000003435 aroyl group Chemical group 0.000 claims description 29
- 125000001424 substituent group Chemical group 0.000 claims description 29
- SOWBFZRMHSNYGE-UHFFFAOYSA-N oxamic acid Chemical compound NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 claims description 28
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 25
- 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 24
- 125000000304 alkynyl group Chemical group 0.000 claims description 24
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 22
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 22
- 230000015572 biosynthetic process Effects 0.000 claims description 22
- 239000011593 sulfur Substances 0.000 claims description 22
- 125000000262 haloalkenyl group Chemical group 0.000 claims description 21
- 239000001301 oxygen Substances 0.000 claims description 21
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 20
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 18
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 18
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 17
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 17
- 125000004994 halo alkoxy alkyl group Chemical group 0.000 claims description 17
- SZPWXAOBLNYOHY-UHFFFAOYSA-N [C]1=CC=NC2=CC=CC=C12 Chemical group [C]1=CC=NC2=CC=CC=C12 SZPWXAOBLNYOHY-UHFFFAOYSA-N 0.000 claims description 16
- 150000001721 carbon Chemical group 0.000 claims description 16
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 claims description 16
- 241000124008 Mammalia Species 0.000 claims description 14
- 235000018936 Vitellaria paradoxa Nutrition 0.000 claims description 14
- 239000008280 blood Substances 0.000 claims description 13
- 210000004369 blood Anatomy 0.000 claims description 13
- 150000003857 carboxamides Chemical class 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 12
- 235000014486 Hydrangea macrophylla Nutrition 0.000 claims description 12
- 208000007536 Thrombosis Diseases 0.000 claims description 12
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 12
- 125000001145 hydrido group Chemical group *[H] 0.000 claims description 11
- 150000001408 amides Chemical class 0.000 claims description 10
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 10
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 9
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 9
- 125000004423 acyloxy group Chemical group 0.000 claims description 8
- 125000005466 alkylenyl group Chemical group 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 150000003254 radicals Chemical class 0.000 claims description 7
- 241001024304 Mino Species 0.000 claims description 6
- 125000003368 amide group Chemical group 0.000 claims description 6
- HKIOYBQGHSTUDB-UHFFFAOYSA-N folpet Chemical group C1=CC=C2C(=O)N(SC(Cl)(Cl)Cl)C(=O)C2=C1 HKIOYBQGHSTUDB-UHFFFAOYSA-N 0.000 claims description 6
- 125000001475 halogen functional group Chemical group 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical group C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 claims description 5
- WFBHRSAKANVBKH-UHFFFAOYSA-N N-hydroxyguanidine Chemical compound NC(=N)NO WFBHRSAKANVBKH-UHFFFAOYSA-N 0.000 claims description 5
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 5
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 3
- 206010051055 Deep vein thrombosis Diseases 0.000 claims description 3
- 206010047249 Venous thrombosis Diseases 0.000 claims description 3
- 206010002388 Angina unstable Diseases 0.000 claims description 2
- 208000007814 Unstable Angina Diseases 0.000 claims description 2
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 2
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 claims 131
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 113
- 125000001153 fluoro group Chemical group F* 0.000 claims 71
- 125000001309 chloro group Chemical group Cl* 0.000 claims 58
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 54
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 52
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 49
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 48
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 46
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 40
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 38
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 36
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 35
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims 34
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 33
- 125000001246 bromo group Chemical group Br* 0.000 claims 32
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims 29
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 28
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 28
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 27
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims 25
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 22
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 22
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 21
- LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 claims 20
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 19
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 18
- 229930192474 thiophene Natural products 0.000 claims 18
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 17
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims 17
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 17
- 125000001589 carboacyl group Chemical group 0.000 claims 15
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims 15
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims 14
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 14
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 14
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 13
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 13
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 13
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 13
- NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 claims 12
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 12
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims 12
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims 12
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 12
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 12
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims 12
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 12
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims 11
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 11
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 11
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 11
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 10
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 10
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 10
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims 10
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 10
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 9
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims 9
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims 9
- 241001092080 Hydrangea Species 0.000 claims 9
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims 9
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 9
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 claims 8
- 125000004273 azetidin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])C1([H])* 0.000 claims 8
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims 8
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 7
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 7
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 7
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 7
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims 6
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims 6
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 6
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims 6
- 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims 6
- 125000004317 1,3,5-triazin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=N1 0.000 claims 5
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims 5
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims 5
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 5
- 125000004398 2-methyl-2-butyl group Chemical group CC(C)(CC)* 0.000 claims 5
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 5
- 125000003974 3-carbamimidamidopropyl group Chemical group C(N)(=N)NCCC* 0.000 claims 5
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims 5
- 125000004917 3-methyl-2-butyl group Chemical group CC(C(C)*)C 0.000 claims 5
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims 5
- 125000004920 4-methyl-2-pentyl group Chemical group CC(CC(C)*)C 0.000 claims 5
- JTBLFVSZLZRVKL-UHFFFAOYSA-N CNN(S(=O)(=O)CN(C)C)NCC Chemical compound CNN(S(=O)(=O)CN(C)C)NCC JTBLFVSZLZRVKL-UHFFFAOYSA-N 0.000 claims 5
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 5
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 5
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 5
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims 5
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims 5
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims 5
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims 5
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 5
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims 5
- 150000003557 thiazoles Chemical class 0.000 claims 5
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 claims 4
- 125000006024 2-pentenyl group Chemical group 0.000 claims 4
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims 4
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 claims 4
- 150000001720 carbohydrates Chemical class 0.000 claims 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 4
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims 4
- 125000006074 1-ethyl-2-butenyl group Chemical group 0.000 claims 3
- 125000006048 1-methyl-2-pentenyl group Chemical group 0.000 claims 3
- 125000006052 1-methyl-3-pentenyl group Chemical group 0.000 claims 3
- HUTNOYOBQPAKIA-UHFFFAOYSA-N 1h-pyrazin-2-one Chemical group OC1=CN=CC=N1 HUTNOYOBQPAKIA-UHFFFAOYSA-N 0.000 claims 3
- FEGNSGBHMBUWFL-UHFFFAOYSA-N 2-(ethoxyamino)acetamide Chemical compound CCONCC(N)=O FEGNSGBHMBUWFL-UHFFFAOYSA-N 0.000 claims 3
- ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 claims 3
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 claims 3
- 125000006040 2-hexenyl group Chemical group 0.000 claims 3
- 125000006029 2-methyl-2-butenyl group Chemical group 0.000 claims 3
- 125000006042 4-hexenyl group Chemical group 0.000 claims 3
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- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 3
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Classifications
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- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
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- C07—ORGANIC CHEMISTRY
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- C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
- C07D253/06—1,2,4-Triazines
- C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
- C07D253/07—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members with hetero atoms, or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13479499P | 1999-05-19 | 1999-05-19 | |
| US60/134,794 | 1999-05-19 | ||
| PCT/US2000/009806 WO2000069832A1 (en) | 1999-05-19 | 2000-05-17 | Substituted polycyclic aryl and heteroaryl pyrymidinones useful as anticoagulants |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2002544262A true JP2002544262A (ja) | 2002-12-24 |
Family
ID=22465042
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000618249A Pending JP2002544262A (ja) | 1999-05-19 | 2000-05-17 | 有用な抗凝血剤としての置換多環式アリールおよびヘテロアリールピリミジノン |
Country Status (22)
| Country | Link |
|---|---|
| EP (1) | EP1178970A1 (ko) |
| JP (1) | JP2002544262A (ko) |
| KR (1) | KR20010114271A (ko) |
| CN (1) | CN1157380C (ko) |
| AR (1) | AR030021A1 (ko) |
| AU (2) | AU771718B2 (ko) |
| BR (1) | BR0010758A (ko) |
| CA (1) | CA2373614A1 (ko) |
| CZ (1) | CZ20014116A3 (ko) |
| EA (1) | EA004867B1 (ko) |
| HU (1) | HUP0201242A3 (ko) |
| IL (1) | IL146243A0 (ko) |
| MX (1) | MXPA01011804A (ko) |
| NO (1) | NO20015604L (ko) |
| NZ (1) | NZ514874A (ko) |
| PE (1) | PE20010229A1 (ko) |
| PL (1) | PL352827A1 (ko) |
| SK (1) | SK15852001A3 (ko) |
| TW (1) | TWI222445B (ko) |
| UY (1) | UY26156A1 (ko) |
| WO (1) | WO2000069832A1 (ko) |
| ZA (2) | ZA200109339B (ko) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008542444A (ja) * | 2005-06-07 | 2008-11-27 | フアーマコペイア・インコーポレイテツド | うつ病およびストレス疾患のためのアジノンおよびジアジノンｖ３阻害剤 |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20010113969A (ko) * | 1999-05-19 | 2001-12-28 | 추후보정 | 항응고제로서의 치환된 폴리시클릭 아릴 및 헤테로아릴우라실 |
| US7015230B1 (en) | 1999-05-19 | 2006-03-21 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl uracils useful for selective inhibition of the coagulation cascade |
| US6458952B1 (en) | 1999-05-19 | 2002-10-01 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl uracils useful for selective inhibition of the coagulation cascade |
| US6653316B1 (en) | 1999-05-19 | 2003-11-25 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl pyrimidinones useful for selective inhibition of the coagulation cascade |
| US6664255B1 (en) | 1999-05-19 | 2003-12-16 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl pyrazinones useful for selective inhibition of the coagulation cascade |
| US6750342B1 (en) | 1999-05-19 | 2004-06-15 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl pyrimidinones useful for selective inhibition of the coagulation cascade |
| US6867217B1 (en) | 1999-05-19 | 2005-03-15 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl pyridones useful for selective inhibition of the coagulation cascade |
| US6716838B1 (en) | 1999-05-19 | 2004-04-06 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl uracils as anticoagulative agents |
| AU2001243598A1 (en) | 2000-03-13 | 2001-09-24 | Pharmacia Corporation | Polycyclic aryl and heteroaryl substituted benzenes useful for selective inhibition of the coagulation cascade |
| AU2001251315A1 (en) | 2000-04-05 | 2001-10-23 | Pharmacia Corporation | Polycyclic aryl and heteroaryl substituted 4-pyridones useful for selective inhibition of the coagulation cascade |
| US6875791B2 (en) | 2000-04-05 | 2005-04-05 | Pharmacia Corporation | Polycyclic aryl and heteroaryl substituted 4-pyrones useful for selective inhibition of the coagulation cascade |
| US20040171616A9 (en) | 2000-04-17 | 2004-09-02 | South Michael S. | Polycyclic aryl and heteroaryl substituted 1,4-quinones useful for selective inhibition of the coagulation cascade |
| AU2001222501A1 (en) * | 2000-05-18 | 2001-11-26 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl pyrimidinones useful for selective inhibition of the coagulation cascade |
| US6710058B2 (en) | 2000-11-06 | 2004-03-23 | Bristol-Myers Squibb Pharma Company | Monocyclic or bicyclic carbocycles and heterocycles as factor Xa inhibitors |
| US7015223B1 (en) | 2000-11-20 | 2006-03-21 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl 1,2,4-triazinones useful for selective inhibition of the coagulation cascade |
| WO2002042272A2 (en) | 2000-11-20 | 2002-05-30 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl pyridines useful for selective inhibition of the coagulation cascade |
| US7119094B1 (en) | 2000-11-20 | 2006-10-10 | Warner-Lambert Company | Substituted polycyclic aryl and heteroarpyl pyrazinones useful for selective inhibition of the coagulation cascade |
| WO2003029216A1 (en) | 2001-10-03 | 2003-04-10 | Pharmacia Corporation | 6-membered heterocyclic compounds useful for selective inhibition of the coagulation cascade |
| AU2002367752A1 (en) | 2001-10-03 | 2003-11-17 | Pharmacia Corporation | Substituted 5-membered polycyclic compounds useful for selective inhibition of the coagulation cascade |
| EP1448534A1 (en) * | 2001-10-03 | 2004-08-25 | Pharmacia Corporation | 6-membered unsaturated heterocyclic compounds useful for selective inhibition ofthe coagulation cascade |
| US7015229B2 (en) | 2002-02-22 | 2006-03-21 | Pfizer Inc | Substituted pyrimidinones and pyrimidinthiones |
| TW200307667A (en) | 2002-05-06 | 2003-12-16 | Bristol Myers Squibb Co | Sulfonylaminovalerolactams and derivatives thereof as factor Xa inhibitors |
| US7217794B2 (en) | 2003-04-02 | 2007-05-15 | Daiamed, Inc. | Compounds and methods for treatment of thrombosis |
| US7182738B2 (en) | 2003-04-23 | 2007-02-27 | Marctec, Llc | Patient monitoring apparatus and method for orthosis and other devices |
| CN104311537B (zh) * | 2014-09-19 | 2016-08-24 | 广东东阳光药业有限公司 | 含有嘧啶酮乙酰基取代基吡唑类化合物及其组合物及用途 |
| CN115779953B (zh) * | 2022-12-19 | 2024-06-21 | 中南大学 | 铜负载碳基单原子材料及其制备方法和应用 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5441960A (en) * | 1992-04-16 | 1995-08-15 | Zeneca Limited | 1-pyrimidinylacetamide human leukocyte elastate inhibitors |
| DE69634122D1 (de) * | 1995-04-27 | 2005-02-03 | Mitsubishi Pharma Corp | Heterocyclische amidverbindungen und deren medizinische verwendung |
-
2000
- 2000-05-17 JP JP2000618249A patent/JP2002544262A/ja active Pending
- 2000-05-17 BR BR0010758-1A patent/BR0010758A/pt not_active IP Right Cessation
- 2000-05-17 MX MXPA01011804A patent/MXPA01011804A/es unknown
- 2000-05-17 EA EA200101214A patent/EA004867B1/ru not_active IP Right Cessation
- 2000-05-17 NZ NZ514874A patent/NZ514874A/en unknown
- 2000-05-17 SK SK1585-2001A patent/SK15852001A3/sk unknown
- 2000-05-17 PL PL00352827A patent/PL352827A1/xx not_active Application Discontinuation
- 2000-05-17 WO PCT/US2000/009806 patent/WO2000069832A1/en not_active Application Discontinuation
- 2000-05-17 CN CNB008077479A patent/CN1157380C/zh not_active Expired - Fee Related
- 2000-05-17 IL IL14624300A patent/IL146243A0/xx unknown
- 2000-05-17 AU AU49734/00A patent/AU771718B2/en not_active Ceased
- 2000-05-17 HU HU0201242A patent/HUP0201242A3/hu unknown
- 2000-05-17 CA CA002373614A patent/CA2373614A1/en not_active Abandoned
- 2000-05-17 CZ CZ20014116A patent/CZ20014116A3/cs unknown
- 2000-05-17 EP EP00931928A patent/EP1178970A1/en not_active Withdrawn
- 2000-05-17 KR KR1020017014753A patent/KR20010114271A/ko not_active Application Discontinuation
- 2000-05-19 UY UY26156A patent/UY26156A1/es not_active Application Discontinuation
- 2000-05-19 AR ARP000102446A patent/AR030021A1/es unknown
- 2000-06-09 PE PE2000000575A patent/PE20010229A1/es not_active Application Discontinuation
- 2000-07-25 TW TW089109595A patent/TWI222445B/zh not_active IP Right Cessation
-
2001
- 2001-11-13 ZA ZA200109339A patent/ZA200109339B/xx unknown
- 2001-11-16 NO NO20015604A patent/NO20015604L/no not_active Application Discontinuation
-
2004
- 2004-01-21 ZA ZA200400448A patent/ZA200400448B/xx unknown
- 2004-05-31 AU AU2004202375A patent/AU2004202375A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008542444A (ja) * | 2005-06-07 | 2008-11-27 | フアーマコペイア・インコーポレイテツド | うつ病およびストレス疾患のためのアジノンおよびジアジノンｖ３阻害剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2004202375A1 (en) | 2004-06-24 |
| IL146243A0 (en) | 2002-07-25 |
| ZA200109339B (en) | 2004-05-26 |
| UY26156A1 (es) | 2000-12-29 |
| PL352827A1 (en) | 2003-09-08 |
| CA2373614A1 (en) | 2000-11-23 |
| PE20010229A1 (es) | 2001-03-07 |
| AU771718B2 (en) | 2004-04-01 |
| AR030021A1 (es) | 2003-08-13 |
| CZ20014116A3 (cs) | 2002-06-12 |
| EP1178970A1 (en) | 2002-02-13 |
| AU4973400A (en) | 2000-12-05 |
| CN1157380C (zh) | 2004-07-14 |
| NO20015604L (no) | 2002-01-11 |
| EA200101214A1 (ru) | 2002-06-27 |
| HUP0201242A2 (hu) | 2002-12-28 |
| WO2000069832A1 (en) | 2000-11-23 |
| NO20015604D0 (no) | 2001-11-16 |
| SK15852001A3 (sk) | 2003-06-03 |
| ZA200400448B (en) | 2004-09-29 |
| KR20010114271A (ko) | 2001-12-31 |
| NZ514874A (en) | 2004-11-26 |
| MXPA01011804A (es) | 2003-09-04 |
| HUP0201242A3 (en) | 2003-02-28 |
| EA004867B1 (ru) | 2004-08-26 |
| CN1351593A (zh) | 2002-05-29 |
| BR0010758A (pt) | 2003-06-10 |
| TWI222445B (en) | 2004-10-21 |
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