SK15852001A3 - Substituované polycyklické arylové a heteroarylové pyrimidinóny použiteľné ako antikoagulanty - Google Patents
Substituované polycyklické arylové a heteroarylové pyrimidinóny použiteľné ako antikoagulanty Download PDFInfo
- Publication number
- SK15852001A3 SK15852001A3 SK1585-2001A SK15852001A SK15852001A3 SK 15852001 A3 SK15852001 A3 SK 15852001A3 SK 15852001 A SK15852001 A SK 15852001A SK 15852001 A3 SK15852001 A3 SK 15852001A3
- Authority
- SK
- Slovakia
- Prior art keywords
- group
- hydrido
- amino
- hydroxy
- optionally substituted
- Prior art date
Links
- -1 heteroaryl pyrimidinones Chemical class 0.000 title claims abstract description 1521
- 239000003146 anticoagulant agent Substances 0.000 title abstract description 9
- 229940127219 anticoagulant drug Drugs 0.000 title abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 19
- 239000000203 mixture Substances 0.000 claims abstract description 13
- 230000001732 thrombotic effect Effects 0.000 claims abstract description 8
- 230000002265 prevention Effects 0.000 claims abstract description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 527
- 150000001721 carbon Chemical group 0.000 claims description 232
- 229910052760 oxygen Inorganic materials 0.000 claims description 209
- 229910052757 nitrogen Inorganic materials 0.000 claims description 202
- 125000000217 alkyl group Chemical group 0.000 claims description 200
- 125000004429 atom Chemical group 0.000 claims description 195
- 229910052717 sulfur Inorganic materials 0.000 claims description 161
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 146
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 145
- 125000001188 haloalkyl group Chemical group 0.000 claims description 143
- 125000001145 hydrido group Chemical group *[H] 0.000 claims description 132
- 125000003282 alkyl amino group Chemical group 0.000 claims description 128
- 125000003545 alkoxy group Chemical group 0.000 claims description 103
- 150000002367 halogens Chemical class 0.000 claims description 102
- 229910052736 halogen Inorganic materials 0.000 claims description 100
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 96
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 95
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 81
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 79
- 125000004414 alkyl thio group Chemical group 0.000 claims description 77
- 125000001424 substituent group Chemical group 0.000 claims description 64
- 125000000033 alkoxyamino group Chemical group 0.000 claims description 61
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 59
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 57
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 52
- 125000000623 heterocyclic group Chemical group 0.000 claims description 51
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 46
- 150000003839 salts Chemical class 0.000 claims description 46
- 125000001072 heteroaryl group Chemical group 0.000 claims description 45
- 125000004076 pyridyl group Chemical group 0.000 claims description 44
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 40
- 125000003118 aryl group Chemical group 0.000 claims description 40
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 40
- 125000003342 alkenyl group Chemical group 0.000 claims description 35
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 35
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 35
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 34
- 125000005518 carboxamido group Chemical group 0.000 claims description 34
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 34
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 34
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 34
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 33
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 33
- 125000004995 haloalkylthio group Chemical group 0.000 claims description 33
- 125000003435 aroyl group Chemical group 0.000 claims description 31
- 125000004043 oxo group Chemical group O=* 0.000 claims description 31
- 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 30
- 125000005843 halogen group Chemical group 0.000 claims description 29
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 27
- 125000000304 alkynyl group Chemical group 0.000 claims description 21
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 21
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 21
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 20
- 125000004994 halo alkoxy alkyl group Chemical group 0.000 claims description 20
- 125000000262 haloalkenyl group Chemical group 0.000 claims description 20
- 239000011593 sulfur Substances 0.000 claims description 20
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 18
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 18
- 239000001301 oxygen Substances 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
- 208000007536 Thrombosis Diseases 0.000 claims description 17
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 17
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 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
- 230000015572 biosynthetic process Effects 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical group OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 claims description 13
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 13
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 11
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 11
- 125000004688 alkyl sulfonyl alkyl group Chemical group 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 9
- 125000005466 alkylenyl group Chemical group 0.000 claims description 9
- 230000002401 inhibitory effect Effects 0.000 claims description 9
- 239000008280 blood Substances 0.000 claims description 8
- 210000004369 blood Anatomy 0.000 claims description 8
- 125000004423 acyloxy group Chemical group 0.000 claims description 7
- 150000001408 amides Chemical class 0.000 claims description 6
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 4
- 208000005189 Embolism Diseases 0.000 claims description 3
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 2
- 208000007814 Unstable Angina Diseases 0.000 claims description 2
- 101150054130 chfr gene Proteins 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 124
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 114
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 60
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 56
- 125000001309 chloro group Chemical group Cl* 0.000 claims 54
- 125000001153 fluoro group Chemical group F* 0.000 claims 54
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 53
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 47
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 45
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 45
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 44
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(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
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 32
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 32
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 31
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 30
- 125000001246 bromo group Chemical group Br* 0.000 claims 30
- 229930192474 thiophene Natural products 0.000 claims 30
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims 29
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 29
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 28
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 23
- 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 19
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims 19
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 18
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[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 18
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 18
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 17
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 16
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])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
- 125000001589 carboacyl group Chemical group 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
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims 14
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 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
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 13
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=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
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 12
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 11
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims 11
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims 11
- 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 11
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)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
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 10
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims 10
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 10
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims 10
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 10
- 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 10
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 9
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims 9
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 9
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims 9
- 239000000460 chlorine Substances 0.000 claims 9
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 9
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 9
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 8
- 125000004273 azetidin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])C1([H])* 0.000 claims 8
- 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 8
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 7
- 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 7
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims 7
- 229910052801 chlorine Inorganic materials 0.000 claims 7
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims 7
- 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims 7
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims 6
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims 6
- 101150065749 Churc1 gene Proteins 0.000 claims 6
- 102100038239 Protein Churchill Human genes 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
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 6
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims 5
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 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
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims 5
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims 5
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 claims 5
- 125000004920 4-methyl-2-pentyl group Chemical group CC(CC(C)*)C 0.000 claims 5
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims 5
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 5
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims 5
- 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 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
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims 5
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims 5
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 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
- 125000004317 1,3,5-triazin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=N1 0.000 claims 4
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 claims 4
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 claims 4
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims 4
- 125000004398 2-methyl-2-butyl group Chemical group CC(C)(CC)* 0.000 claims 4
- 125000004917 3-methyl-2-butyl group Chemical group CC(C(C)*)C 0.000 claims 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 4
- 229910052794 bromium Inorganic materials 0.000 claims 4
- 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 4
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 4
- 125000000714 pyrimidinyl group Chemical group 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
- 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
- 125000006040 2-hexenyl group Chemical group 0.000 claims 3
- 125000006029 2-methyl-2-butenyl group Chemical group 0.000 claims 3
- 125000006024 2-pentenyl group Chemical group 0.000 claims 3
- 125000006041 3-hexenyl group Chemical group 0.000 claims 3
- 125000006042 4-hexenyl group Chemical group 0.000 claims 3
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 3
- 125000004432 carbon atom Chemical group C* 0.000 claims 3
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims 3
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims 3
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 claims 2
- 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 2
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 2
- 125000003944 tolyl group Chemical group 0.000 claims 2
- 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 claims 1
- 125000006037 1-ethyl-2-propenyl group Chemical group 0.000 claims 1
- 125000006075 1-ethyl-3-butenyl group Chemical group 0.000 claims 1
- 125000006028 1-methyl-2-butenyl group Chemical group 0.000 claims 1
- 125000006030 1-methyl-3-butenyl group Chemical group 0.000 claims 1
- 125000006055 1-methyl-4-pentenyl group Chemical group 0.000 claims 1
- 125000006031 2-methyl-3-butenyl group Chemical group 0.000 claims 1
- 125000006032 3-methyl-3-butenyl group Chemical group 0.000 claims 1
- 125000006043 5-hexenyl group Chemical group 0.000 claims 1
- YCIPQJTZJGUXND-UHFFFAOYSA-N Aglaia odorata Alkaloid Natural products C1=CC(OC)=CC=C1C1(C(C=2C(=O)N3CCCC3=NC=22)C=3C=CC=CC=3)C2(O)C2=C(OC)C=C(OC)C=C2O1 YCIPQJTZJGUXND-UHFFFAOYSA-N 0.000 claims 1
- 125000006414 CCl Chemical group ClC* 0.000 claims 1
- 206010014498 Embolic stroke Diseases 0.000 claims 1
- 206010014522 Embolism venous Diseases 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 208000001435 Thromboembolism Diseases 0.000 claims 1
- 230000001093 anti-cancer Effects 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 230000001269 cardiogenic effect Effects 0.000 claims 1
- 238000002512 chemotherapy Methods 0.000 claims 1
- 125000000068 chlorophenyl group Chemical group 0.000 claims 1
- 125000004188 dichlorophenyl group Chemical group 0.000 claims 1
- 239000002319 fibrinogen receptor antagonist Substances 0.000 claims 1
- 150000002240 furans Chemical class 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- LOTBYPQQWICYBB-UHFFFAOYSA-N methyl n-hexyl-n-[2-(hexylamino)ethyl]carbamate Chemical group CCCCCCNCCN(C(=O)OC)CCCCCC LOTBYPQQWICYBB-UHFFFAOYSA-N 0.000 claims 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims 1
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims 1
- 208000004043 venous thromboembolism Diseases 0.000 claims 1
- 230000015271 coagulation Effects 0.000 abstract description 8
- 238000005345 coagulation Methods 0.000 abstract description 8
- 238000000034 method Methods 0.000 abstract description 5
- 208000026106 cerebrovascular disease Diseases 0.000 abstract description 4
- 208000029078 coronary artery disease Diseases 0.000 abstract description 4
- 238000002560 therapeutic procedure 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
- 210000004351 coronary vessel Anatomy 0.000 abstract description 2
- 239000003112 inhibitor Substances 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- 125000000392 cycloalkenyl group Chemical group 0.000 description 30
- 125000002252 acyl group Chemical group 0.000 description 29
- 239000011669 selenium Substances 0.000 description 28
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 18
- 125000004487 4-tetrahydropyranyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 13
- 150000004678 hydrides Chemical group 0.000 description 12
- 125000004104 aryloxy group Chemical group 0.000 description 11
- 125000005160 aryl oxy alkyl group Chemical group 0.000 description 10
- 206010053567 Coagulopathies Diseases 0.000 description 9
- 125000005347 halocycloalkyl group Chemical group 0.000 description 9
- 108010073385 Fibrin Proteins 0.000 description 8
- 102000009123 Fibrin Human genes 0.000 description 8
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 8
- 125000001769 aryl amino group Chemical group 0.000 description 8
- 230000035602 clotting Effects 0.000 description 8
- 229950003499 fibrin Drugs 0.000 description 8
- 125000005326 heteroaryloxy alkyl group Chemical group 0.000 description 8
- 125000004687 alkyl sulfinyl alkyl group Chemical group 0.000 description 7
- 125000005110 aryl thio group Chemical group 0.000 description 7
- 125000002573 ethenylidene group Chemical group [*]=C=C([H])[H] 0.000 description 7
- 125000005241 heteroarylamino group Chemical group 0.000 description 7
- 125000005452 alkenyloxyalkyl group Chemical group 0.000 description 6
- 125000002947 alkylene group Chemical group 0.000 description 6
- 125000001691 aryl alkyl amino group Chemical group 0.000 description 6
- 125000005164 aryl thioalkyl group Chemical group 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 6
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 5
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 5
- 125000005354 acylalkyl group Chemical group 0.000 description 5
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 5
- 239000003114 blood coagulation factor Substances 0.000 description 5
- 125000005356 cycloalkylalkenyl group Chemical group 0.000 description 5
- 125000005144 cycloalkylsulfonyl group Chemical group 0.000 description 5
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 description 5
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 5
- 108090000190 Thrombin Proteins 0.000 description 4
- 125000003302 alkenyloxy group Chemical group 0.000 description 4
- 125000005021 aminoalkenyl group Chemical group 0.000 description 4
- 125000005135 aryl sulfinyl group Chemical group 0.000 description 4
- 125000005111 carboxyalkoxy group Chemical group 0.000 description 4
- 125000005149 cycloalkylsulfinyl group Chemical group 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229960004072 thrombin Drugs 0.000 description 4
- 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
- 125000005421 aryl sulfonamido group Chemical group 0.000 description 3
- 150000003857 carboxamides Chemical class 0.000 description 3
- 125000004966 cyanoalkyl group Chemical group 0.000 description 3
- 125000004465 cycloalkenyloxy group Chemical group 0.000 description 3
- 125000000000 cycloalkoxy group Chemical group 0.000 description 3
- 125000004858 cycloalkoxyalkyl group Chemical group 0.000 description 3
- 125000006310 cycloalkyl amino group Chemical group 0.000 description 3
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 description 3
- 125000004475 heteroaralkyl group Chemical group 0.000 description 3
- 125000005553 heteroaryloxy group Chemical group 0.000 description 3
- 125000005150 heteroarylsulfinyl group Chemical group 0.000 description 3
- 125000005368 heteroarylthio group Chemical group 0.000 description 3
- 125000004468 heterocyclylthio group Chemical group 0.000 description 3
- 238000005304 joining Methods 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 3
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 2
- 125000005330 8 membered heterocyclic group Chemical group 0.000 description 2
- 108010062466 Enzyme Precursors Proteins 0.000 description 2
- 102000010911 Enzyme Precursors Human genes 0.000 description 2
- 108010074860 Factor Xa Proteins 0.000 description 2
- 125000004442 acylamino group Chemical group 0.000 description 2
- 125000005237 alkyleneamino group Chemical group 0.000 description 2
- 125000005018 aryl alkenyl group Chemical group 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 125000004967 formylalkyl group Chemical group 0.000 description 2
- 125000006769 halocycloalkoxy group Chemical group 0.000 description 2
- 230000023597 hemostasis Effects 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229910000679 solder Inorganic materials 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 102100023804 Coagulation factor VII Human genes 0.000 description 1
- 108010023321 Factor VII Proteins 0.000 description 1
- 108010054265 Factor VIIa Proteins 0.000 description 1
- 108010074105 Factor Va Proteins 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- ZUTMWBXMAHNQCX-UHFFFAOYSA-N NC=1C(=NC(=NC=1)O)NC(=O)C Chemical class NC=1C(=NC(=NC=1)O)NC(=O)C ZUTMWBXMAHNQCX-UHFFFAOYSA-N 0.000 description 1
- IGFMYNAGGDCVOB-UHFFFAOYSA-N NC=1C(=NC(NC1)=O)CC(=O)N Chemical class NC=1C(=NC(NC1)=O)CC(=O)N IGFMYNAGGDCVOB-UHFFFAOYSA-N 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 206010061876 Obstruction Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 102000002262 Thromboplastin Human genes 0.000 description 1
- 208000032109 Transient ischaemic attack Diseases 0.000 description 1
- RLTPOGIGJILWFY-UHFFFAOYSA-N [N].O=C1N=CC=CN1 Chemical compound [N].O=C1N=CC=CN1 RLTPOGIGJILWFY-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 125000005140 aralkylsulfonyl group Chemical group 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 208000015294 blood coagulation disease Diseases 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 239000003601 chymase inhibitor Substances 0.000 description 1
- 229940105772 coagulation factor vii Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229940012414 factor viia Drugs 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- QYNDTTJOWNQBII-UHFFFAOYSA-N furo[3,4-c]pyridine Chemical compound C1=NC=CC2=COC=C21 QYNDTTJOWNQBII-UHFFFAOYSA-N 0.000 description 1
- 125000004440 haloalkylsulfinyl group Chemical group 0.000 description 1
- 230000002439 hemostatic effect Effects 0.000 description 1
- 125000004404 heteroalkyl group Chemical group 0.000 description 1
- 125000005844 heterocyclyloxy group Chemical group 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical group C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000004963 sulfonylalkyl group Chemical group 0.000 description 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—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
- 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
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- 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
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (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)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13479499P | 1999-05-19 | 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 |
|---|---|
| SK15852001A3 true SK15852001A3 (sk) | 2003-06-03 |
Family
ID=22465042
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1585-2001A SK15852001A3 (sk) | 1999-05-19 | 2000-05-17 | Substituované polycyklické arylové a heteroarylové pyrimidinóny použiteľné ako antikoagulanty |
Country Status (22)
| Country | Link |
|---|---|
| EP (1) | EP1178970A1 (zh) |
| JP (1) | JP2002544262A (zh) |
| KR (1) | KR20010114271A (zh) |
| CN (1) | CN1157380C (zh) |
| AR (1) | AR030021A1 (zh) |
| AU (2) | AU771718B2 (zh) |
| BR (1) | BR0010758A (zh) |
| CA (1) | CA2373614A1 (zh) |
| CZ (1) | CZ20014116A3 (zh) |
| EA (1) | EA004867B1 (zh) |
| HU (1) | HUP0201242A3 (zh) |
| IL (1) | IL146243A0 (zh) |
| MX (1) | MXPA01011804A (zh) |
| NO (1) | NO20015604L (zh) |
| NZ (1) | NZ514874A (zh) |
| PE (1) | PE20010229A1 (zh) |
| PL (1) | PL352827A1 (zh) |
| SK (1) | SK15852001A3 (zh) |
| TW (1) | TWI222445B (zh) |
| UY (1) | UY26156A1 (zh) |
| WO (1) | WO2000069832A1 (zh) |
| ZA (2) | ZA200109339B (zh) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6750342B1 (en) | 1999-05-19 | 2004-06-15 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl pyrimidinones useful for selective inhibition of the coagulation cascade |
| JP2002544263A (ja) * | 1999-05-19 | 2002-12-24 | ファルマシア・コーポレイション | 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ウラシル |
| US6867217B1 (en) | 1999-05-19 | 2005-03-15 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl pyridones 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 |
| 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 |
| US7015230B1 (en) | 1999-05-19 | 2006-03-21 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl uracils useful for selective inhibition of the coagulation cascade |
| WO2001068605A1 (en) | 2000-03-13 | 2001-09-20 | 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 |
| WO2001077097A2 (en) | 2000-04-05 | 2001-10-18 | Pharmacia Corporation | Polycyclic aryl and heteroaryl substituted 4-pyrones useful for selective inhibition of the coagulation cascade |
| US6686484B2 (en) | 2000-04-17 | 2004-02-03 | Pharmacia Corporation | 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 |
| CA2430037A1 (en) | 2000-11-20 | 2002-05-30 | Michael S. South | 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 |
| 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 |
| BR0213092A (pt) | 2001-10-03 | 2004-10-19 | Pharmacia Corp | Compostos heterocìclicos de 6 elementos úteis para a inibição seletiva da cascata de coagulação |
| US7105559B2 (en) | 2001-10-03 | 2006-09-12 | Pharmacia Corporation | Substituted 5-membered polycyclic compounds useful for selective inhibition of the coagulation cascade |
| MXPA04003167A (es) * | 2001-10-03 | 2004-07-08 | Pharmacia Corp | Compuestos heterociclicos insaturados de 6 miembros utiles para la inhibicion selectiva de la cascada de coagulacion. |
| WO2003072107A1 (en) * | 2002-02-22 | 2003-09-04 | Pharmacia & Upjohn Company | 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 |
| CA2610400A1 (en) * | 2005-06-07 | 2006-12-14 | Pharmacopeia, Inc. | Azinone and diazinone v3 inhibitors for depression and stress disorders |
| 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 |
| AU2020396565C1 (en) * | 2019-12-04 | 2025-05-15 | Omeros Corporation | MASP-2 inhibitors and methods of use |
| 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 |
| EP0826671B1 (en) * | 1995-04-27 | 2004-12-29 | Mitsubishi Pharma Corporation | Heterocyclic amide compounds and medicinal use of the same |
-
2000
- 2000-05-17 MX MXPA01011804A patent/MXPA01011804A/es unknown
- 2000-05-17 CZ CZ20014116A patent/CZ20014116A3/cs unknown
- 2000-05-17 CA CA002373614A patent/CA2373614A1/en not_active Abandoned
- 2000-05-17 EA EA200101214A patent/EA004867B1/ru not_active IP Right Cessation
- 2000-05-17 SK SK1585-2001A patent/SK15852001A3/sk unknown
- 2000-05-17 JP JP2000618249A patent/JP2002544262A/ja active Pending
- 2000-05-17 HU HU0201242A patent/HUP0201242A3/hu unknown
- 2000-05-17 WO PCT/US2000/009806 patent/WO2000069832A1/en not_active Ceased
- 2000-05-17 BR BR0010758-1A patent/BR0010758A/pt not_active IP Right Cessation
- 2000-05-17 AU AU49734/00A patent/AU771718B2/en not_active Ceased
- 2000-05-17 KR KR1020017014753A patent/KR20010114271A/ko not_active Withdrawn
- 2000-05-17 CN CNB008077479A patent/CN1157380C/zh not_active Expired - Fee Related
- 2000-05-17 NZ NZ514874A patent/NZ514874A/en unknown
- 2000-05-17 PL PL00352827A patent/PL352827A1/xx not_active Application Discontinuation
- 2000-05-17 IL IL14624300A patent/IL146243A0/xx unknown
- 2000-05-17 EP EP00931928A patent/EP1178970A1/en not_active Withdrawn
- 2000-05-19 AR ARP000102446A patent/AR030021A1/es unknown
- 2000-05-19 UY UY26156A patent/UY26156A1/es not_active Application Discontinuation
- 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
Also Published As
| Publication number | Publication date |
|---|---|
| AU2004202375A1 (en) | 2004-06-24 |
| KR20010114271A (ko) | 2001-12-31 |
| EA200101214A1 (ru) | 2002-06-27 |
| CN1351593A (zh) | 2002-05-29 |
| MXPA01011804A (es) | 2003-09-04 |
| PL352827A1 (en) | 2003-09-08 |
| ZA200109339B (en) | 2004-05-26 |
| NO20015604D0 (no) | 2001-11-16 |
| EA004867B1 (ru) | 2004-08-26 |
| CA2373614A1 (en) | 2000-11-23 |
| HUP0201242A2 (hu) | 2002-12-28 |
| NZ514874A (en) | 2004-11-26 |
| EP1178970A1 (en) | 2002-02-13 |
| CN1157380C (zh) | 2004-07-14 |
| WO2000069832A1 (en) | 2000-11-23 |
| HUP0201242A3 (en) | 2003-02-28 |
| PE20010229A1 (es) | 2001-03-07 |
| TWI222445B (en) | 2004-10-21 |
| ZA200400448B (en) | 2004-09-29 |
| JP2002544262A (ja) | 2002-12-24 |
| NO20015604L (no) | 2002-01-11 |
| AU771718B2 (en) | 2004-04-01 |
| UY26156A1 (es) | 2000-12-29 |
| CZ20014116A3 (cs) | 2002-06-12 |
| AR030021A1 (es) | 2003-08-13 |
| BR0010758A (pt) | 2003-06-10 |
| IL146243A0 (en) | 2002-07-25 |
| AU4973400A (en) | 2000-12-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SK15852001A3 (sk) | Substituované polycyklické arylové a heteroarylové pyrimidinóny použiteľné ako antikoagulanty | |
| AU771740B2 (en) | Substituted polycyclic aryl and heteroaryl uracils as anticoagulative agents | |
| KR20010113970A (ko) | 응고 캐스케이드의 선택적 억제에 유용한 치환 폴리시클릭아릴 및 헤테로아릴 피리돈 | |
| US6664255B1 (en) | Substituted polycyclic aryl and heteroaryl pyrazinones useful for selective inhibition of the coagulation cascade | |
| KR20010113971A (ko) | 응고 케스케이드의 선택적 억제에 유용한 치환 폴리시클릭아릴 및 헤테로아릴 피라지논 | |
| US6653316B1 (en) | Substituted polycyclic aryl and heteroaryl pyrimidinones useful for selective inhibition of the coagulation cascade | |
| US6458952B1 (en) | Substituted polycyclic aryl and heteroaryl uracils useful for selective inhibition of the coagulation cascade | |
| US6750342B1 (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 | |
| US7015223B1 (en) | Substituted polycyclic aryl and heteroaryl 1,2,4-triazinones useful for selective inhibition of the coagulation cascade | |
| US6908919B2 (en) | Substituted polycyclic aryl and heteroaryl pyrazinones useful for selective inhibition of the coagulation cascade | |
| WO2001087851A1 (en) | Substituted polycyclic aryl and heteroaryl pyrimidinones useful for selective inhibition of the coagulation cascade | |
| US6716838B1 (en) | Substituted polycyclic aryl and heteroaryl uracils as anticoagulative agents | |
| 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 | |
| EP1586565A1 (en) | Substituted polycyclic aryl and heteroaryl pyrazinones useful for selective inhibition of the coagulation cascade |