SK15862001A3 - Substituované polycyklické aryl a heteroaryl pyridóny užitočné na selektívnu inhibíciu koagulačnej kaskády - Google Patents
Substituované polycyklické aryl a heteroaryl pyridóny užitočné na selektívnu inhibíciu koagulačnej kaskády Download PDFInfo
- Publication number
- SK15862001A3 SK15862001A3 SK1586-2001A SK15862001A SK15862001A3 SK 15862001 A3 SK15862001 A3 SK 15862001A3 SK 15862001 A SK15862001 A SK 15862001A SK 15862001 A3 SK15862001 A3 SK 15862001A3
- Authority
- SK
- Slovakia
- Prior art keywords
- group
- hydrido
- amino
- hydroxy
- carbon
- Prior art date
Links
- -1 heteroaryl pyridones Chemical class 0.000 title claims abstract description 1800
- 230000015271 coagulation Effects 0.000 title abstract description 11
- 238000005345 coagulation Methods 0.000 title abstract description 11
- 230000005764 inhibitory process Effects 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 48
- 238000011282 treatment Methods 0.000 claims abstract description 9
- 230000002265 prevention Effects 0.000 claims abstract description 7
- 230000001732 thrombotic effect Effects 0.000 claims abstract description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 453
- 125000001145 hydrido group Chemical group *[H] 0.000 claims description 388
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 312
- 229910052757 nitrogen Inorganic materials 0.000 claims description 197
- 229910052760 oxygen Inorganic materials 0.000 claims description 175
- 125000000217 alkyl group Chemical group 0.000 claims description 161
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 155
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 148
- 229910052717 sulfur Inorganic materials 0.000 claims description 134
- 125000001188 haloalkyl group Chemical group 0.000 claims description 118
- 125000004429 atom Chemical group 0.000 claims description 113
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 108
- 125000003282 alkyl amino group Chemical group 0.000 claims description 102
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 83
- 125000003545 alkoxy group Chemical group 0.000 claims description 81
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 65
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 63
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 60
- 125000004414 alkyl thio group Chemical group 0.000 claims description 59
- 125000004432 carbon atom Chemical group C* 0.000 claims description 56
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 53
- 125000000033 alkoxyamino group Chemical group 0.000 claims description 52
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 48
- 150000004820 halides Chemical class 0.000 claims description 48
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 47
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 44
- 150000001721 carbon Chemical group 0.000 claims description 40
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 38
- 125000001072 heteroaryl group Chemical group 0.000 claims description 36
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 34
- 125000003118 aryl group Chemical group 0.000 claims description 34
- 125000000623 heterocyclic group Chemical group 0.000 claims description 33
- 125000003342 alkenyl group Chemical group 0.000 claims description 32
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 32
- 229910052736 halogen Inorganic materials 0.000 claims description 32
- 150000002367 halogens Chemical class 0.000 claims description 32
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 32
- 125000004995 haloalkylthio group Chemical group 0.000 claims description 31
- 125000004043 oxo group Chemical group O=* 0.000 claims description 30
- 125000005518 carboxamido group Chemical group 0.000 claims description 28
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 28
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 28
- 125000004076 pyridyl group Chemical group 0.000 claims description 28
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 26
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 26
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 26
- 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 25
- 125000005843 halogen group Chemical group 0.000 claims description 23
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 20
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 19
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 19
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
- 125000003435 aroyl group Chemical group 0.000 claims description 17
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 17
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 16
- 230000015572 biosynthetic process Effects 0.000 claims description 16
- 208000007536 Thrombosis Diseases 0.000 claims description 15
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 15
- 125000004994 halo alkoxy alkyl group Chemical group 0.000 claims description 15
- 125000000304 alkynyl group Chemical group 0.000 claims description 14
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 claims description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
- 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 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 239000011593 sulfur Substances 0.000 claims description 12
- 230000002401 inhibitory effect Effects 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 125000006413 ring segment Chemical group 0.000 claims description 11
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 10
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 10
- 125000000262 haloalkenyl group Chemical group 0.000 claims description 10
- 239000008280 blood Substances 0.000 claims description 9
- 210000004369 blood Anatomy 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 9
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 9
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 8
- 125000005466 alkylenyl group Chemical group 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 8
- 125000004487 4-tetrahydropyranyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 6
- 125000004423 acyloxy group Chemical group 0.000 claims description 6
- 125000005647 linker group Chemical group 0.000 claims description 6
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 6
- 230000002792 vascular Effects 0.000 claims description 5
- 208000005189 Embolism Diseases 0.000 claims description 4
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 4
- 125000004688 alkyl sulfonyl alkyl group Chemical group 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 206010002383 Angina Pectoris Diseases 0.000 claims description 3
- HUTNOYOBQPAKIA-UHFFFAOYSA-N 1h-pyrazin-2-one Chemical group OC1=CN=CC=N1 HUTNOYOBQPAKIA-UHFFFAOYSA-N 0.000 claims description 2
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 2
- 125000003277 amino group Chemical group 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 132
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 120
- 125000001153 fluoro group Chemical group F* 0.000 claims 101
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 93
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 71
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 66
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 64
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 60
- 125000001309 chloro group Chemical group Cl* 0.000 claims 60
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 59
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 48
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 44
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims 44
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims 42
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 42
- 125000001246 bromo group Chemical group Br* 0.000 claims 39
- 229910014033 C-OH Inorganic materials 0.000 claims 37
- 229910014570 C—OH Inorganic materials 0.000 claims 37
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 36
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 32
- 229930192474 thiophene Natural products 0.000 claims 32
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 30
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 29
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 29
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 24
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims 23
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 22
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 22
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims 21
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 21
- LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 claims 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 20
- 125000001589 carboacyl group Chemical group 0.000 claims 19
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims 18
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 17
- 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 17
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 17
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 17
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 17
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims 16
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims 16
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 16
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 16
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 16
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims 15
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 15
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 15
- 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 15
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 14
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims 14
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 13
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims 13
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 12
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 12
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims 12
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 12
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims 12
- 125000004273 azetidin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])C1([H])* 0.000 claims 12
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 12
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims 12
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 12
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 12
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims 11
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 11
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims 11
- 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 11
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims 10
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 10
- 101150065749 Churc1 gene Proteins 0.000 claims 10
- 102100038239 Protein Churchill Human genes 0.000 claims 10
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 9
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims 9
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims 9
- 125000003974 3-carbamimidamidopropyl group Chemical group C(N)(=N)NCCC* 0.000 claims 8
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims 8
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims 8
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims 7
- 125000004398 2-methyl-2-butyl group Chemical group CC(C)(CC)* 0.000 claims 7
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 7
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims 7
- 125000004917 3-methyl-2-butyl group Chemical group CC(C(C)*)C 0.000 claims 7
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims 7
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 claims 7
- 125000004920 4-methyl-2-pentyl group Chemical group CC(CC(C)*)C 0.000 claims 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 7
- 229910052794 bromium Inorganic materials 0.000 claims 7
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims 7
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 7
- 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims 7
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 7
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 claims 6
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 6
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims 6
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims 6
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 6
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims 6
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 6
- 150000002240 furans Chemical class 0.000 claims 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 6
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims 6
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims 6
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims 6
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 6
- 125000006074 1-ethyl-2-butenyl group Chemical group 0.000 claims 5
- 125000006048 1-methyl-2-pentenyl group Chemical group 0.000 claims 5
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 5
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 claims 5
- 125000006040 2-hexenyl group Chemical group 0.000 claims 5
- 125000006041 3-hexenyl group Chemical group 0.000 claims 5
- 125000006042 4-hexenyl group Chemical group 0.000 claims 5
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 5
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 5
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 5
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims 5
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 5
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 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
- ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 claims 4
- 125000006029 2-methyl-2-butenyl group Chemical group 0.000 claims 4
- 125000006024 2-pentenyl group Chemical group 0.000 claims 4
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 claims 4
- CCQWVVMBBHILMN-UHFFFAOYSA-N C(C(OCl(OC(F)(F)F)F)(F)F)(F)F Chemical compound C(C(OCl(OC(F)(F)F)F)(F)F)(F)F CCQWVVMBBHILMN-UHFFFAOYSA-N 0.000 claims 4
- 125000006414 CCl Chemical group ClC* 0.000 claims 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 4
- 229910052801 chlorine Inorganic materials 0.000 claims 4
- 239000000460 chlorine Substances 0.000 claims 4
- 125000006037 1-ethyl-2-propenyl group Chemical group 0.000 claims 3
- 125000006075 1-ethyl-3-butenyl group Chemical group 0.000 claims 3
- 125000006028 1-methyl-2-butenyl group Chemical group 0.000 claims 3
- 125000006030 1-methyl-3-butenyl group Chemical group 0.000 claims 3
- 125000006052 1-methyl-3-pentenyl group Chemical group 0.000 claims 3
- 125000006031 2-methyl-3-butenyl group Chemical group 0.000 claims 3
- 125000006043 5-hexenyl group Chemical group 0.000 claims 3
- PBHQTWZEARSGNC-UHFFFAOYSA-N [1,1,2,2-tetrafluoro-2-(trifluoromethoxy)ethyl] hypofluorite Chemical compound FOC(F)(F)C(F)(F)OC(F)(F)F PBHQTWZEARSGNC-UHFFFAOYSA-N 0.000 claims 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 3
- 239000003937 drug carrier Substances 0.000 claims 3
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 3
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims 3
- 125000006055 1-methyl-4-pentenyl group Chemical group 0.000 claims 2
- 125000006032 3-methyl-3-butenyl group Chemical group 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 208000001435 Thromboembolism Diseases 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 claims 2
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 claims 2
- 125000006850 spacer group Chemical group 0.000 claims 2
- 125000004317 1,3,5-triazin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=N1 0.000 claims 1
- YCWRFIYBUQBHJI-UHFFFAOYSA-N 2-(4-aminophenyl)acetonitrile Chemical group NC1=CC=C(CC#N)C=C1 YCWRFIYBUQBHJI-UHFFFAOYSA-N 0.000 claims 1
- 125000006058 4-methyl-4-pentenyl group Chemical group 0.000 claims 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims 1
- 101000957333 Homo sapiens Muscleblind-like protein 3 Proteins 0.000 claims 1
- 102100038751 Muscleblind-like protein 3 Human genes 0.000 claims 1
- CHEXHYHWTJLVJJ-UHFFFAOYSA-N N-(1,2-dihydropyridin-2-yl)acetamide Chemical compound CC(=O)NC1NC=CC=C1 CHEXHYHWTJLVJJ-UHFFFAOYSA-N 0.000 claims 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims 1
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims 1
- 230000001269 cardiogenic effect Effects 0.000 claims 1
- 238000002512 chemotherapy Methods 0.000 claims 1
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims 1
- 239000002319 fibrinogen receptor antagonist Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims 1
- 125000003373 pyrazinyl group Chemical group 0.000 claims 1
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 claims 1
- 125000006300 thietan-3-yl group Chemical group [H]C1([H])SC([H])([H])C1([H])* 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims 1
- SMBZJSVIKJMSFP-UHFFFAOYSA-N trifluoromethyl hypofluorite Chemical compound FOC(F)(F)F SMBZJSVIKJMSFP-UHFFFAOYSA-N 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 9
- 239000003146 anticoagulant agent Substances 0.000 abstract description 6
- 229940127219 anticoagulant drug Drugs 0.000 abstract description 5
- 208000026106 cerebrovascular disease Diseases 0.000 abstract description 4
- 238000000034 method Methods 0.000 abstract description 4
- 102000012479 Serine Proteases Human genes 0.000 abstract description 3
- 108010022999 Serine Proteases Proteins 0.000 abstract description 3
- 238000002560 therapeutic procedure Methods 0.000 abstract description 3
- 208000029078 coronary artery disease Diseases 0.000 abstract description 2
- 210000004351 coronary vessel Anatomy 0.000 abstract description 2
- 239000003112 inhibitor Substances 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 abstract 1
- 125000002252 acyl group Chemical group 0.000 description 11
- 108090000190 Thrombin Proteins 0.000 description 10
- 229960004072 thrombin Drugs 0.000 description 10
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 9
- 108010073385 Fibrin Proteins 0.000 description 9
- 102000009123 Fibrin Human genes 0.000 description 9
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 9
- 229950003499 fibrin Drugs 0.000 description 9
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 6
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 6
- 239000003114 blood coagulation factor Substances 0.000 description 6
- 206010053567 Coagulopathies Diseases 0.000 description 4
- 150000001408 amides Chemical group 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000035602 clotting Effects 0.000 description 4
- XXRUAAOADAPPII-UHFFFAOYSA-N 6-(trifluoromethyl)-1h-pyridin-2-one Chemical class OC1=CC=CC(C(F)(F)F)=N1 XXRUAAOADAPPII-UHFFFAOYSA-N 0.000 description 3
- 200000000007 Arterial disease Diseases 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 150000003869 acetamides Chemical class 0.000 description 3
- 125000005021 aminoalkenyl group Chemical group 0.000 description 3
- 125000005160 aryl oxy alkyl group Chemical group 0.000 description 3
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 3
- 125000004104 aryloxy group Chemical group 0.000 description 3
- 125000002573 ethenylidene group Chemical group [*]=C=C([H])[H] 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 125000006769 halocycloalkoxy group Chemical group 0.000 description 3
- 125000005347 halocycloalkyl group Chemical group 0.000 description 3
- 125000005326 heteroaryloxy alkyl group Chemical group 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000011669 selenium Substances 0.000 description 3
- 108010062466 Enzyme Precursors Proteins 0.000 description 2
- 102000010911 Enzyme Precursors Human genes 0.000 description 2
- 125000005452 alkenyloxyalkyl group Chemical group 0.000 description 2
- 125000004687 alkyl sulfinyl alkyl group Chemical group 0.000 description 2
- 125000005140 aralkylsulfonyl group Chemical group 0.000 description 2
- 125000001691 aryl alkyl amino group Chemical group 0.000 description 2
- 125000001769 aryl amino group Chemical group 0.000 description 2
- 125000005135 aryl sulfinyl group Chemical group 0.000 description 2
- 125000005421 aryl sulfonamido group Chemical group 0.000 description 2
- 125000005110 aryl thio group Chemical group 0.000 description 2
- 125000005164 aryl thioalkyl group Chemical group 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 150000003857 carboxamides Chemical class 0.000 description 2
- 125000004465 cycloalkenyloxy group Chemical group 0.000 description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 description 2
- 125000004858 cycloalkoxyalkyl group Chemical group 0.000 description 2
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 description 2
- 125000004475 heteroaralkyl group Chemical group 0.000 description 2
- 125000004447 heteroarylalkenyl group Chemical group 0.000 description 2
- 125000005241 heteroarylamino group Chemical group 0.000 description 2
- 125000005150 heteroarylsulfinyl group Chemical group 0.000 description 2
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 description 2
- 125000005368 heteroarylthio group Chemical group 0.000 description 2
- 125000004468 heterocyclylthio group Chemical group 0.000 description 2
- 230000013632 homeostatic process Effects 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- QDPBFNSXUVIBTG-UHFFFAOYSA-N 3,4-diamino-6-methyl-1h-pyridin-2-one Chemical class CC1=CC(N)=C(N)C(=O)N1 QDPBFNSXUVIBTG-UHFFFAOYSA-N 0.000 description 1
- JEAVIRYCMBDJIU-UHFFFAOYSA-N 6-methyl-1h-pyridin-2-one Chemical group CC1=CC=CC(O)=N1 JEAVIRYCMBDJIU-UHFFFAOYSA-N 0.000 description 1
- 206010003178 Arterial thrombosis Diseases 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 206010014498 Embolic stroke Diseases 0.000 description 1
- 108010074105 Factor Va Proteins 0.000 description 1
- 108010074860 Factor Xa Proteins 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- IJCKBIINTQEGLY-UHFFFAOYSA-N N(4)-acetylcytosine Chemical class CC(=O)NC1=CC=NC(=O)N1 IJCKBIINTQEGLY-UHFFFAOYSA-N 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 206010038563 Reocclusion Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 102000002262 Thromboplastin Human genes 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 125000003302 alkenyloxy group Chemical group 0.000 description 1
- 125000005263 alkylenediamine group Chemical group 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 208000028922 artery disease Diseases 0.000 description 1
- 125000005018 aryl alkenyl group Chemical group 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 206010061592 cardiac fibrillation Diseases 0.000 description 1
- 239000003601 chymase inhibitor Substances 0.000 description 1
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
- 125000004966 cyanoalkyl group Chemical group 0.000 description 1
- 125000006310 cycloalkyl amino group Chemical group 0.000 description 1
- 125000005356 cycloalkylalkenyl group Chemical group 0.000 description 1
- 125000005144 cycloalkylsulfonyl group Chemical group 0.000 description 1
- 230000002600 fibrillogenic effect Effects 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 125000005553 heteroaryloxy group Chemical group 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- FVZVCSNXTFCBQU-UHFFFAOYSA-N phosphanyl Chemical group [PH2] FVZVCSNXTFCBQU-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 150000005299 pyridinones Chemical group 0.000 description 1
- TYLGVQVJCVFREB-UHFFFAOYSA-N pyrido[3,4-b]pyrazine Chemical class C1=NC=CC2=NC=CN=C21 TYLGVQVJCVFREB-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 229960003766 thrombin (human) Drugs 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/76—Nitrogen atoms to which a second hetero atom is attached
- C07D213/77—Hydrazine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- 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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Quinoline Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13481199P | 1999-05-19 | 1999-05-19 | |
| PCT/US2000/008220 WO2000069826A1 (en) | 1999-05-19 | 2000-05-15 | Substituted polycyclic aryl and heteroaryl pyridones useful for selective inhibition of the coagulation cascade |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK15862001A3 true SK15862001A3 (sk) | 2002-08-06 |
Family
ID=22465131
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1586-2001A SK15862001A3 (sk) | 1999-05-19 | 2000-05-15 | Substituované polycyklické aryl a heteroaryl pyridóny užitočné na selektívnu inhibíciu koagulačnej kaskády |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP1178964A1 (xx) |
| JP (1) | JP2002544260A (xx) |
| KR (1) | KR20010113970A (xx) |
| CN (1) | CN1378534A (xx) |
| AR (1) | AR029635A1 (xx) |
| AU (1) | AU771928B2 (xx) |
| BR (1) | BR0011272A (xx) |
| CA (1) | CA2373509A1 (xx) |
| CZ (1) | CZ20014117A3 (xx) |
| EA (1) | EA005367B1 (xx) |
| HU (1) | HUP0201996A3 (xx) |
| IL (1) | IL146244A0 (xx) |
| MX (1) | MXPA01011805A (xx) |
| MY (1) | MY138303A (xx) |
| NO (1) | NO20015606L (xx) |
| NZ (1) | NZ514875A (xx) |
| PL (1) | PL352403A1 (xx) |
| SK (1) | SK15862001A3 (xx) |
| UY (1) | UY26154A1 (xx) |
| WO (1) | WO2000069826A1 (xx) |
| ZA (2) | ZA200109340B (xx) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6664255B1 (en) | 1999-05-19 | 2003-12-16 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl pyrazinones 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 |
| US6716838B1 (en) | 1999-05-19 | 2004-04-06 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl uracils as anticoagulative agents |
| US6653316B1 (en) | 1999-05-19 | 2003-11-25 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl pyrimidinones 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 |
| US7015230B1 (en) | 1999-05-19 | 2006-03-21 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl uracils useful for selective inhibition of the coagulation cascade |
| US6852761B2 (en) | 2000-03-13 | 2005-02-08 | Pharmacia Corporation | Polycyclic aryl and heteroaryl substituted benzenes useful for selective inhibition of the coagulation cascade |
| CA2405306A1 (en) | 2000-04-05 | 2001-10-18 | Pharmacia Corporation | Polycyclic aryl and heteroaryl substituted 4-pyridones useful for selective inhibition of the coagulation cascade |
| JP2004505014A (ja) | 2000-04-05 | 2004-02-19 | ファルマシア・コーポレーション | 凝血カスケードの選択的阻害に有用な多環式アリールおよびヘテロアリール置換された４−ピロン類 |
| AU2001255399A1 (en) * | 2000-04-14 | 2001-10-30 | Corvas International, Inc. | Pyridine and pyrazine derivatives as thrombin inhibitors |
| WO2001079155A2 (en) | 2000-04-17 | 2001-10-25 | Pharmacia Corporation | Polycyclic aryl and heteroaryl substituted 1,4-quinones useful for selective inhibition of the coagulation cascade |
| AU2001217827A1 (en) * | 2000-05-18 | 2001-11-26 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl pyridones 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 |
| 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 |
| 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 |
| CN100575345C (zh) | 2000-12-28 | 2009-12-30 | 盐野义制药株式会社 | 对2型大麻素受体具有结合活性的吡啶酮衍生物 |
| EP1438292A1 (en) | 2001-10-03 | 2004-07-21 | Pharmacia Corporation | 6-membered heterocyclic compounds useful for selective inhibition of the coagulation cascade |
| WO2003093242A2 (en) | 2001-10-03 | 2003-11-13 | Pharmacia Corporation | Substituted 5-membered polycyclic compounds useful for selective inhibition of the coagulation cascade |
| US7262211B2 (en) * | 2001-12-04 | 2007-08-28 | Dendreon Corporation | Aromatic heterocyclic non-covalent inhibitors of urokinase and blood vessel formation |
| TW200307667A (en) | 2002-05-06 | 2003-12-16 | Bristol Myers Squibb Co | Sulfonylaminovalerolactams and derivatives thereof as factor Xa inhibitors |
| ES2534804T3 (es) | 2010-05-07 | 2015-04-28 | Glaxosmithkline Llc | Indazoles |
| TWI633089B (zh) * | 2013-03-28 | 2018-08-21 | 拜耳製藥股份有限公司 | 經取代的酮基吡啶衍生物 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2224437A1 (en) * | 1995-06-27 | 1997-01-16 | Merck & Co., Inc. | Pyridinone-thrombin inhibitors |
| EP0923372A4 (en) * | 1996-02-22 | 2001-09-05 | Merck & Co Inc | PYRIDINONE THROMBINE INHIBITORS |
| EP0932608A1 (en) * | 1996-10-11 | 1999-08-04 | Cor Therapeutics, Inc. | SELECTIVE FACTOR Xa INHIBITORS |
| US5792779A (en) * | 1997-02-19 | 1998-08-11 | Merck & Co., Inc. | Pyridinone thrombin inhibitors |
| WO1998042342A1 (en) * | 1997-03-24 | 1998-10-01 | Merck & Co., Inc. | Thrombin inhibitors |
| IL123986A (en) * | 1997-04-24 | 2011-10-31 | Organon Nv | Medicinal compounds |
| IL133627A0 (en) * | 1997-06-26 | 2001-04-30 | Lilly Co Eli | Antithrombotic agents |
| CA2301520A1 (en) * | 1997-09-05 | 1999-03-11 | Merck & Co., Inc. | Pyrazinone thrombin inhibitors |
| ATE344246T1 (de) * | 1997-11-26 | 2006-11-15 | Ortho Mcneil Pharm Inc | Heteroaryl aminoguanidin- und alkoxyguanidinderivate und ihre verwendung als proteasehemmer |
| JP2002525370A (ja) * | 1998-09-28 | 2002-08-13 | メルク エンド カムパニー インコーポレーテッド | トロンビン阻害剤 |
| WO2000026211A1 (en) * | 1998-10-30 | 2000-05-11 | Merck & Co., Inc. | Thrombin inhibitors |
| CA2348530A1 (en) * | 1998-10-30 | 2000-05-11 | Merck & Co., Inc. | Thrombin inhibitors |
| FR2786482B1 (fr) * | 1998-11-27 | 2002-08-09 | Synthelabo | Nouveaux derives de 2-pyridone, leur preparation et leur application en therapeutique |
-
2000
- 2000-05-15 CA CA002373509A patent/CA2373509A1/en not_active Abandoned
- 2000-05-15 EA EA200101213A patent/EA005367B1/ru not_active IP Right Cessation
- 2000-05-15 IL IL14624400A patent/IL146244A0/xx unknown
- 2000-05-15 MX MXPA01011805A patent/MXPA01011805A/es active IP Right Grant
- 2000-05-15 EP EP00930092A patent/EP1178964A1/en not_active Withdrawn
- 2000-05-15 PL PL00352403A patent/PL352403A1/xx not_active Application Discontinuation
- 2000-05-15 AU AU47973/00A patent/AU771928B2/en not_active Ceased
- 2000-05-15 JP JP2000618243A patent/JP2002544260A/ja active Pending
- 2000-05-15 CZ CZ20014117A patent/CZ20014117A3/cs unknown
- 2000-05-15 WO PCT/US2000/008220 patent/WO2000069826A1/en not_active Application Discontinuation
- 2000-05-15 NZ NZ514875A patent/NZ514875A/en unknown
- 2000-05-15 HU HU0201996A patent/HUP0201996A3/hu unknown
- 2000-05-15 CN CN00810182A patent/CN1378534A/zh active Pending
- 2000-05-15 BR BR0011272-0A patent/BR0011272A/pt not_active IP Right Cessation
- 2000-05-15 KR KR1020017014751A patent/KR20010113970A/ko not_active Withdrawn
- 2000-05-15 SK SK1586-2001A patent/SK15862001A3/sk unknown
- 2000-05-19 UY UY26154A patent/UY26154A1/es not_active Application Discontinuation
- 2000-05-19 MY MYPI20002212A patent/MY138303A/en unknown
- 2000-05-19 AR ARP000102448A patent/AR029635A1/es unknown
-
2001
- 2001-11-13 ZA ZA200109340A patent/ZA200109340B/xx unknown
- 2001-11-16 NO NO20015606A patent/NO20015606L/no not_active Application Discontinuation
-
2004
- 2004-01-21 ZA ZA200400449A patent/ZA200400449B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL146244A0 (en) | 2002-07-25 |
| MY138303A (en) | 2009-05-29 |
| JP2002544260A (ja) | 2002-12-24 |
| UY26154A1 (es) | 2000-12-29 |
| ZA200109340B (en) | 2004-05-26 |
| CN1378534A (zh) | 2002-11-06 |
| WO2000069826A1 (en) | 2000-11-23 |
| PL352403A1 (en) | 2003-08-25 |
| NO20015606L (no) | 2002-01-21 |
| HUP0201996A2 (en) | 2002-09-28 |
| NZ514875A (en) | 2004-10-29 |
| ZA200400449B (en) | 2004-11-24 |
| CZ20014117A3 (cs) | 2002-05-15 |
| CA2373509A1 (en) | 2000-11-23 |
| NO20015606D0 (no) | 2001-11-16 |
| BR0011272A (pt) | 2002-05-07 |
| MXPA01011805A (es) | 2003-09-04 |
| AU4797300A (en) | 2000-12-05 |
| EA005367B1 (ru) | 2005-02-24 |
| EP1178964A1 (en) | 2002-02-13 |
| EA200101213A1 (ru) | 2002-04-25 |
| AU771928B2 (en) | 2004-04-08 |
| KR20010113970A (ko) | 2001-12-28 |
| HUP0201996A3 (en) | 2002-12-28 |
| AR029635A1 (es) | 2003-07-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6624180B2 (en) | Substituted polycyclic aryl and heteroaryl pyridines useful for selective inhibition of the coagulation cascade | |
| SK15862001A3 (sk) | Substituované polycyklické aryl a heteroaryl pyridóny užitočné na selektívnu inhibíciu koagulačnej kaskády | |
| AU771718B2 (en) | Substituted polycyclic aryl and heteroaryl pyrymidinones useful as anticoagulants | |
| AU771740B2 (en) | Substituted polycyclic aryl and heteroaryl uracils as anticoagulative agents | |
| AU775229B2 (en) | Substituted polycyclic aryl and heteroaryl pyrazinones useful for selective inhibition of the coagulation cascade | |
| US6664255B1 (en) | Substituted polycyclic aryl and heteroaryl pyrazinones useful for selective inhibition of the coagulation cascade | |
| US6653316B1 (en) | Substituted polycyclic aryl and heteroaryl pyrimidinones useful for selective inhibition of the coagulation cascade | |
| US6867217B1 (en) | Substituted polycyclic aryl and heteroaryl pyridones useful for selective inhibition of the coagulation cascade | |
| US6750342B1 (en) | Substituted polycyclic aryl and heteroaryl pyrimidinones useful for selective inhibition of the coagulation cascade | |
| US7015223B1 (en) | Substituted polycyclic aryl and heteroaryl 1,2,4-triazinones useful for selective inhibition of the coagulation cascade | |
| US6906068B1 (en) | Substituted polycyclic aryl and heteroaryl 1,2,4 - triazinones useful as anticoagulants | |
| US7119094B1 (en) | Substituted polycyclic aryl and heteroarpyl pyrazinones useful for selective inhibition of the coagulation cascade | |
| US20040068113A1 (en) | Substituted polycyclic aryl and heteroaryl pyridines useful for selective inhibition of the coagulation cascade | |
| EP1586565A1 (en) | Substituted polycyclic aryl and heteroaryl pyrazinones useful for selective inhibition of the coagulation cascade |