HRP20090468T1 - Urea antagonisti p2y1 receptora korisni u liječenju trombotičkih stanja - Google Patents
Urea antagonisti p2y1 receptora korisni u liječenju trombotičkih stanja Download PDFInfo
- Publication number
- HRP20090468T1 HRP20090468T1 HR20090468T HRP20090468T HRP20090468T1 HR P20090468 T1 HRP20090468 T1 HR P20090468T1 HR 20090468 T HR20090468 T HR 20090468T HR P20090468 T HRP20090468 T HR P20090468T HR P20090468 T1 HRP20090468 T1 HR P20090468T1
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- Prior art keywords
- substituted
- phenyl
- alkyl
- crfrf
- heterocyclic ring
- Prior art date
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- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 title claims 15
- 239000004202 carbamide Substances 0.000 title claims 15
- 102000016927 Purinergic P2Y1 Receptors Human genes 0.000 title 1
- 108010028935 Purinergic P2Y1 Receptors Proteins 0.000 title 1
- 239000005557 antagonist Substances 0.000 title 1
- 230000001732 thrombotic effect Effects 0.000 title 1
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract 101
- -1 4,4,5,5-tetramethyl-1,3,2-dioxaborolanyl Chemical group 0.000 claims abstract 73
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract 71
- 229910052760 oxygen Inorganic materials 0.000 claims abstract 71
- 125000005842 heteroatom Chemical group 0.000 claims abstract 59
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract 56
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract 44
- 229910052731 fluorine Inorganic materials 0.000 claims abstract 43
- 229910052801 chlorine Inorganic materials 0.000 claims abstract 41
- 229910052794 bromium Inorganic materials 0.000 claims abstract 32
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract 30
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract 29
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims abstract 27
- 150000001875 compounds Chemical class 0.000 claims abstract 23
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract 22
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 20
- 229910052799 carbon Inorganic materials 0.000 claims abstract 20
- 125000001960 7 membered carbocyclic group Chemical group 0.000 claims abstract 17
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims abstract 14
- 125000003545 alkoxy group Chemical group 0.000 claims abstract 14
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims abstract 13
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract 12
- 229910052717 sulfur Inorganic materials 0.000 claims abstract 12
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims abstract 11
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims abstract 9
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims abstract 7
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract 7
- 125000003118 aryl group Chemical group 0.000 claims abstract 7
- 125000004438 haloalkoxy group Chemical group 0.000 claims abstract 7
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims abstract 6
- 150000003839 salts Chemical class 0.000 claims abstract 6
- 239000012453 solvate Substances 0.000 claims abstract 6
- 125000001624 naphthyl group Chemical group 0.000 claims abstract 2
- 229910020008 S(O) Inorganic materials 0.000 claims 105
- 125000000217 alkyl group Chemical group 0.000 claims 39
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 38
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 36
- 229910052739 hydrogen Inorganic materials 0.000 claims 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 19
- 229910052710 silicon Inorganic materials 0.000 claims 16
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims 12
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 11
- 125000004429 atom Chemical group 0.000 claims 11
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 11
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims 8
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 7
- 150000001721 carbon Chemical group 0.000 claims 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 7
- 125000003003 spiro group Chemical group 0.000 claims 7
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 claims 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 6
- 208000035475 disorder Diseases 0.000 claims 6
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 6
- 125000000335 thiazolyl group Chemical group 0.000 claims 6
- 230000009424 thromboembolic effect Effects 0.000 claims 6
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 5
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims 5
- 125000002541 furyl group Chemical group 0.000 claims 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 5
- 125000004076 pyridyl group Chemical group 0.000 claims 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 4
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims 4
- 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 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 4
- 125000001544 thienyl group Chemical group 0.000 claims 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 3
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims 3
- 125000000062 cyclohexylmethoxy group Chemical group [H]C([H])(O*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 3
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims 3
- 229910052757 nitrogen Inorganic materials 0.000 claims 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 3
- HYZDJHJGTFYYCK-UHFFFAOYSA-N spiro[indole-3,4'-piperidine] Chemical compound C1CNCCC21C1=CC=CC=C1N=C2 HYZDJHJGTFYYCK-UHFFFAOYSA-N 0.000 claims 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 claims 2
- LOFVUPFIGBAWCL-UHFFFAOYSA-N 1-[2-(4-methyl-3,4-dihydro-2h-quinolin-1-yl)phenyl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C12=CC=CC=C2C(C)CCN1C1=CC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 LOFVUPFIGBAWCL-UHFFFAOYSA-N 0.000 claims 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 2
- DMCLNIZKWQGPTM-UHFFFAOYSA-N 5-bromo-2-[(3-octoxyphenyl)methylsulfanyl]benzoic acid Chemical compound CCCCCCCCOC1=CC=CC(CSC=2C(=CC(Br)=CC=2)C(O)=O)=C1 DMCLNIZKWQGPTM-UHFFFAOYSA-N 0.000 claims 2
- 206010047249 Venous thrombosis Diseases 0.000 claims 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- 125000005921 isopentoxy group Chemical group 0.000 claims 2
- 208000010125 myocardial infarction Diseases 0.000 claims 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 2
- 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 2
- 125000003386 piperidinyl group Chemical group 0.000 claims 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 2
- PEUPUKDBCPLDIH-UHFFFAOYSA-N 1,2,4-triazole Chemical group C1=NC=N[N]1 PEUPUKDBCPLDIH-UHFFFAOYSA-N 0.000 claims 1
- VDWKAMQYMKFDGJ-UHFFFAOYSA-N 1,3-bis[2-(3,3-dimethyl-2h-indol-1-yl)pyridin-3-yl]urea Chemical compound C1C(C)(C)C2=CC=CC=C2N1C1=NC=CC=C1NC(=O)NC1=CC=CN=C1N1CC(C)(C)C2=CC=CC=C21 VDWKAMQYMKFDGJ-UHFFFAOYSA-N 0.000 claims 1
- YWHDYWJSIMVZPX-UHFFFAOYSA-N 1-(2-carbazol-9-ylpyridin-3-yl)-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(=O)NC1=CC=CN=C1N1C2=CC=CC=C2C2=CC=CC=C21 YWHDYWJSIMVZPX-UHFFFAOYSA-N 0.000 claims 1
- GEJIPPAZXMEKNZ-UHFFFAOYSA-N 1-(2-indol-1-ylpyridin-3-yl)-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(=O)NC1=CC=CN=C1N1C2=CC=CC=C2C=C1 GEJIPPAZXMEKNZ-UHFFFAOYSA-N 0.000 claims 1
- VLVYGPOBUIHHAE-UHFFFAOYSA-N 1-(2-spiro[2h-indole-3,1'-cyclopentane]-1-ylphenyl)-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(=O)NC1=CC=CC=C1N1C2=CC=CC=C2C2(CCCC2)C1 VLVYGPOBUIHHAE-UHFFFAOYSA-N 0.000 claims 1
- DINOSKMIZHXYDP-UHFFFAOYSA-N 1-(2-spiro[2h-indole-3,1'-cyclopropane]-1-ylphenyl)-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(=O)NC1=CC=CC=C1N1C2=CC=CC=C2C2(CC2)C1 DINOSKMIZHXYDP-UHFFFAOYSA-N 0.000 claims 1
- JJASALXIXQIGMZ-UHFFFAOYSA-N 1-(4-acetylphenyl)-3-[2-(3,3-dimethyl-2h-indol-1-yl)pyridin-3-yl]urea Chemical compound C1=CC(C(=O)C)=CC=C1NC(=O)NC1=CC=CN=C1N1C2=CC=CC=C2C(C)(C)C1 JJASALXIXQIGMZ-UHFFFAOYSA-N 0.000 claims 1
- JHNSPALSBCMLFK-UHFFFAOYSA-N 1-(4-tert-butylphenyl)-3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)phenyl]urea Chemical compound C1=CC(C(C)(C)C)=CC=C1NC(=O)NC1=CC=CC=C1N1C2=CC=CC=C2OCC1 JHNSPALSBCMLFK-UHFFFAOYSA-N 0.000 claims 1
- UKCBXPKZIITHTF-UHFFFAOYSA-N 1-(4-tert-butylphenyl)-3-[2-(3,3-dimethyl-2h-indol-1-yl)phenyl]urea Chemical compound C1=CC(C(C)(C)C)=CC=C1NC(=O)NC1=CC=CC=C1N1C2=CC=CC=C2C(C)(C)C1 UKCBXPKZIITHTF-UHFFFAOYSA-N 0.000 claims 1
- DKIAAKJMIPLHGV-UHFFFAOYSA-N 1-(4-tert-butylphenyl)-3-[2-(3,4-dihydro-2h-quinolin-1-yl)phenyl]urea Chemical compound C1=CC(C(C)(C)C)=CC=C1NC(=O)NC1=CC=CC=C1N1C2=CC=CC=C2CCC1 DKIAAKJMIPLHGV-UHFFFAOYSA-N 0.000 claims 1
- AOIAAKXCMGNRJJ-UHFFFAOYSA-N 1-(4-tert-butylphenyl)-3-[2-(3-methylindol-1-yl)phenyl]urea Chemical compound C12=CC=CC=C2C(C)=CN1C1=CC=CC=C1NC(=O)NC1=CC=C(C(C)(C)C)C=C1 AOIAAKXCMGNRJJ-UHFFFAOYSA-N 0.000 claims 1
- XFIAOQQYXCGDIW-UHFFFAOYSA-N 1-[2-(2,2-dimethyl-3h-1,4-benzoxazin-4-yl)phenyl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C12=CC=CC=C2OC(C)(C)CN1C1=CC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 XFIAOQQYXCGDIW-UHFFFAOYSA-N 0.000 claims 1
- QFFJSBMLUIUWDZ-UHFFFAOYSA-N 1-[2-(2,3,4,5-tetrahydro-1-benzazepin-1-yl)phenyl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(=O)NC1=CC=CC=C1N1C2=CC=CC=C2CCCC1 QFFJSBMLUIUWDZ-UHFFFAOYSA-N 0.000 claims 1
- QZHSNXPJBHKISL-UHFFFAOYSA-N 1-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)phenyl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(=O)NC1=CC=CC=C1N1C2=CC=CC=C2OCC1 QZHSNXPJBHKISL-UHFFFAOYSA-N 0.000 claims 1
- CJWUSALUJUGZED-UHFFFAOYSA-N 1-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)pyridin-3-yl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(=O)NC1=CC=CN=C1N1C2=CC=CC=C2OCC1 CJWUSALUJUGZED-UHFFFAOYSA-N 0.000 claims 1
- JPVGPAVDZNKJBB-UHFFFAOYSA-N 1-[2-(2-methyl-2,3-dihydroindol-1-yl)pyridin-3-yl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound CC1CC2=CC=CC=C2N1C1=NC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 JPVGPAVDZNKJBB-UHFFFAOYSA-N 0.000 claims 1
- AWPACHBRNPJTJV-UHFFFAOYSA-N 1-[2-(2-methylindol-1-yl)phenyl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound CC1=CC2=CC=CC=C2N1C1=CC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 AWPACHBRNPJTJV-UHFFFAOYSA-N 0.000 claims 1
- REXIWLOVDSYKOF-UHFFFAOYSA-N 1-[2-(2-tert-butylphenoxy)pyridin-3-yl]-3-[2-(3,3-dimethyl-2h-indol-1-yl)phenyl]urea Chemical compound CC(C)(C)C1=CC=CC=C1OC1=NC=CC=C1NC(=O)NC1=CC=CC=C1N1C2=CC=CC=C2C(C)(C)C1 REXIWLOVDSYKOF-UHFFFAOYSA-N 0.000 claims 1
- REMMHUBNJVPSLV-UHFFFAOYSA-N 1-[2-(2-tert-butylphenoxy)pyridin-3-yl]-3-[2-(3,3-dimethyl-2h-indol-1-yl)pyridin-3-yl]urea Chemical compound CC(C)(C)C1=CC=CC=C1OC1=NC=CC=C1NC(=O)NC1=CC=CN=C1N1C2=CC=CC=C2C(C)(C)C1 REMMHUBNJVPSLV-UHFFFAOYSA-N 0.000 claims 1
- GYKCLACFAZJLOM-UHFFFAOYSA-N 1-[2-(3,3-dimethyl-2h-indol-1-yl)phenyl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C12=CC=CC=C2C(C)(C)CN1C1=CC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 GYKCLACFAZJLOM-UHFFFAOYSA-N 0.000 claims 1
- SVZKEGBBEMLNOZ-UHFFFAOYSA-N 1-[2-(3,3-dimethyl-2h-indol-1-yl)pyridin-3-yl]-3-(4-methylphenyl)urea Chemical compound C1=CC(C)=CC=C1NC(=O)NC1=CC=CN=C1N1C2=CC=CC=C2C(C)(C)C1 SVZKEGBBEMLNOZ-UHFFFAOYSA-N 0.000 claims 1
- FLOSTSHWSBYXJK-UHFFFAOYSA-N 1-[2-(3,3-dimethyl-2h-indol-1-yl)pyridin-3-yl]-3-[3-[1-(2-methylpropoxy)ethyl]phenyl]urea Chemical compound CC(C)COC(C)C1=CC=CC(NC(=O)NC=2C(=NC=CC=2)N2C3=CC=CC=C3C(C)(C)C2)=C1 FLOSTSHWSBYXJK-UHFFFAOYSA-N 0.000 claims 1
- YWCWWPHEGIYNRQ-UHFFFAOYSA-N 1-[2-(3,3-dimethyl-2h-indol-1-yl)pyridin-3-yl]-3-[3-[1-[[4-(trifluoromethyl)phenyl]methoxy]ethyl]phenyl]urea Chemical compound C=1C=CC(NC(=O)NC=2C(=NC=CC=2)N2C3=CC=CC=C3C(C)(C)C2)=CC=1C(C)OCC1=CC=C(C(F)(F)F)C=C1 YWCWWPHEGIYNRQ-UHFFFAOYSA-N 0.000 claims 1
- JRISVVBXOYQRMC-UHFFFAOYSA-N 1-[2-(3,3-dimethyl-2h-indol-1-yl)pyridin-3-yl]-3-[3-[1-[furan-2-ylmethyl(methyl)amino]ethyl]phenyl]urea Chemical compound C=1C=CC(NC(=O)NC=2C(=NC=CC=2)N2C3=CC=CC=C3C(C)(C)C2)=CC=1C(C)N(C)CC1=CC=CO1 JRISVVBXOYQRMC-UHFFFAOYSA-N 0.000 claims 1
- VAAAVLYHAKZTJL-UHFFFAOYSA-N 1-[2-(3,3-dimethyl-2h-indol-1-yl)pyridin-3-yl]-3-[3-[1-[methyl(thiophen-2-ylmethyl)amino]ethyl]phenyl]urea Chemical compound C=1C=CC(NC(=O)NC=2C(=NC=CC=2)N2C3=CC=CC=C3C(C)(C)C2)=CC=1C(C)N(C)CC1=CC=CS1 VAAAVLYHAKZTJL-UHFFFAOYSA-N 0.000 claims 1
- UOMLGZPBHKLNEG-UHFFFAOYSA-N 1-[2-(3,3-dimethyl-2h-indol-1-yl)pyridin-3-yl]-3-[3-[1-[methyl-[[4-(trifluoromethyl)phenyl]methyl]amino]ethyl]phenyl]urea Chemical compound C=1C=CC(NC(=O)NC=2C(=NC=CC=2)N2C3=CC=CC=C3C(C)(C)C2)=CC=1C(C)N(C)CC1=CC=C(C(F)(F)F)C=C1 UOMLGZPBHKLNEG-UHFFFAOYSA-N 0.000 claims 1
- GPJRMPHHMBOOAY-UHFFFAOYSA-N 1-[2-(3,3-dimethyl-2h-indol-1-yl)pyridin-3-yl]-3-[4-(1-hydroxyethyl)phenyl]urea Chemical compound C1=CC(C(O)C)=CC=C1NC(=O)NC1=CC=CN=C1N1C2=CC=CC=C2C(C)(C)C1 GPJRMPHHMBOOAY-UHFFFAOYSA-N 0.000 claims 1
- ZAPYCZXUTQRITJ-UHFFFAOYSA-N 1-[2-(3,3-dimethyl-2h-indol-1-yl)pyridin-3-yl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C12=CC=CC=C2C(C)(C)CN1C1=NC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 ZAPYCZXUTQRITJ-UHFFFAOYSA-N 0.000 claims 1
- ASAONUKCNBIUEL-UHFFFAOYSA-N 1-[2-(3,4,4a,5,6,7,8,8a-octahydro-2h-quinolin-1-yl)pyridin-3-yl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(=O)NC1=CC=CN=C1N1C2CCCCC2CCC1 ASAONUKCNBIUEL-UHFFFAOYSA-N 0.000 claims 1
- BLHBKMAJQLLUEL-UHFFFAOYSA-N 1-[2-(3,4-dihydro-2h-quinolin-1-yl)phenyl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(=O)NC1=CC=CC=C1N1C2=CC=CC=C2CCC1 BLHBKMAJQLLUEL-UHFFFAOYSA-N 0.000 claims 1
- JGACRMXBPNXEJK-UHFFFAOYSA-N 1-[2-(3,4-dihydro-2h-quinolin-1-yl)pyridin-3-yl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(=O)NC1=CC=CN=C1N1C2=CC=CC=C2CCC1 JGACRMXBPNXEJK-UHFFFAOYSA-N 0.000 claims 1
- DUKYXMVRDWTFNT-UHFFFAOYSA-N 1-[2-(3-ethyl-2,3-dihydroindol-1-yl)phenyl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C12=CC=CC=C2C(CC)CN1C1=CC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 DUKYXMVRDWTFNT-UHFFFAOYSA-N 0.000 claims 1
- BLWGMWAETYEFAK-UHFFFAOYSA-N 1-[2-(3-methyl-2,3-dihydroindol-1-yl)pyridin-3-yl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C12=CC=CC=C2C(C)CN1C1=NC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 BLWGMWAETYEFAK-UHFFFAOYSA-N 0.000 claims 1
- BNTXLQPLYABDJI-UHFFFAOYSA-N 1-[2-(3-methylindol-1-yl)phenyl]-3-(3-methylphenyl)urea Chemical compound C12=CC=CC=C2C(C)=CN1C1=CC=CC=C1NC(=O)NC1=CC=CC(C)=C1 BNTXLQPLYABDJI-UHFFFAOYSA-N 0.000 claims 1
- BPWRHXZFNVVPRF-UHFFFAOYSA-N 1-[2-(3-methylindol-1-yl)phenyl]-3-(4-methylphenyl)urea Chemical compound C12=CC=CC=C2C(C)=CN1C1=CC=CC=C1NC(=O)NC1=CC=C(C)C=C1 BPWRHXZFNVVPRF-UHFFFAOYSA-N 0.000 claims 1
- OXNZMYYOFALHCO-UHFFFAOYSA-N 1-[2-(3-methylindol-1-yl)phenyl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C12=CC=CC=C2C(C)=CN1C1=CC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 OXNZMYYOFALHCO-UHFFFAOYSA-N 0.000 claims 1
- PAMCJSWNRUXDCB-UHFFFAOYSA-N 1-[2-(3-methylindol-1-yl)pyridin-3-yl]-3-(3-methylphenyl)urea Chemical compound C12=CC=CC=C2C(C)=CN1C1=NC=CC=C1NC(=O)NC1=CC=CC(C)=C1 PAMCJSWNRUXDCB-UHFFFAOYSA-N 0.000 claims 1
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- LGFVTDNRYVUXDC-UHFFFAOYSA-N 1-[2-(3-methylindol-1-yl)pyridin-3-yl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C12=CC=CC=C2C(C)=CN1C1=NC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 LGFVTDNRYVUXDC-UHFFFAOYSA-N 0.000 claims 1
- WJDPSXIDDMFMPB-UHFFFAOYSA-N 1-[2-(4,4-dimethyl-2,3-dihydroquinolin-1-yl)phenyl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C12=CC=CC=C2C(C)(C)CCN1C1=CC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 WJDPSXIDDMFMPB-UHFFFAOYSA-N 0.000 claims 1
- WFBIIKCFAHENBM-UHFFFAOYSA-N 1-[2-(4,4-dimethyl-2,3-dihydroquinolin-1-yl)pyridin-3-yl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C12=CC=CC=C2C(C)(C)CCN1C1=NC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 WFBIIKCFAHENBM-UHFFFAOYSA-N 0.000 claims 1
- YQLCNOKNJHVDLX-UHFFFAOYSA-N 1-[2-(4-chloroindol-1-yl)pyridin-3-yl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(=O)NC1=CC=CN=C1N1C2=CC=CC(Cl)=C2C=C1 YQLCNOKNJHVDLX-UHFFFAOYSA-N 0.000 claims 1
- CYQQAMNVBGQLCF-UHFFFAOYSA-N 1-[2-(4-hydroxy-4-phenyl-2,3,4a,5,6,7,8,8a-octahydroquinolin-1-yl)phenyl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C12CCCCC2C(O)(C=2C=CC=CC=2)CCN1C1=CC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 CYQQAMNVBGQLCF-UHFFFAOYSA-N 0.000 claims 1
- VNZCYOMPWAFPQP-UHFFFAOYSA-N 1-[2-(4-methoxyindol-1-yl)pyridin-3-yl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C1=CC=2C(OC)=CC=CC=2N1C1=NC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 VNZCYOMPWAFPQP-UHFFFAOYSA-N 0.000 claims 1
- LUAFYSGRSJFMFG-UHFFFAOYSA-N 1-[2-(4-methyl-2,3-dihydroquinoxalin-1-yl)phenyl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C12=CC=CC=C2N(C)CCN1C1=CC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 LUAFYSGRSJFMFG-UHFFFAOYSA-N 0.000 claims 1
- IEBOWSPUCMMSCM-UHFFFAOYSA-N 1-[2-(4-methylindol-1-yl)pyridin-3-yl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C1=CC=2C(C)=CC=CC=2N1C1=NC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 IEBOWSPUCMMSCM-UHFFFAOYSA-N 0.000 claims 1
- MXSZCFQQWUFZRT-UHFFFAOYSA-N 1-[2-(5-methoxyindol-1-yl)pyridin-3-yl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C1=CC2=CC(OC)=CC=C2N1C1=NC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 MXSZCFQQWUFZRT-UHFFFAOYSA-N 0.000 claims 1
- QPFRSWSXJCOYSY-UHFFFAOYSA-N 1-[2-(5-methylindol-1-yl)pyridin-3-yl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C1=CC2=CC(C)=CC=C2N1C1=NC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 QPFRSWSXJCOYSY-UHFFFAOYSA-N 0.000 claims 1
- WUSJSAKHFYUVST-UHFFFAOYSA-N 1-[2-(6-fluoroindol-1-yl)pyridin-3-yl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C12=CC(F)=CC=C2C=CN1C1=NC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 WUSJSAKHFYUVST-UHFFFAOYSA-N 0.000 claims 1
- GSPHUDDWZJTMCG-UHFFFAOYSA-N 1-[2-(6-methylindol-1-yl)pyridin-3-yl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C12=CC(C)=CC=C2C=CN1C1=NC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 GSPHUDDWZJTMCG-UHFFFAOYSA-N 0.000 claims 1
- ZXJBQKBVJVCOPU-UHFFFAOYSA-N 1-[2-[3-(2-cyanopropan-2-yl)indol-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C12=CC=CC=C2C(C(C)(C#N)C)=CN1C1=CC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 ZXJBQKBVJVCOPU-UHFFFAOYSA-N 0.000 claims 1
- BXBGTQSGSLOHQZ-UHFFFAOYSA-N 1-[4-(3,3-dimethyl-2h-indol-1-yl)pyridin-3-yl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C12=CC=CC=C2C(C)(C)CN1C1=CC=NC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 BXBGTQSGSLOHQZ-UHFFFAOYSA-N 0.000 claims 1
- QFPIUBDXPAYMGI-UHFFFAOYSA-N 1-[4-[3-(dimethylamino)-2,2-dimethylpropoxy]phenyl]-3-[2-(4,4-dimethyl-2,3-dihydroquinolin-1-yl)phenyl]urea Chemical compound C1=CC(OCC(C)(C)CN(C)C)=CC=C1NC(=O)NC1=CC=CC=C1N1C2=CC=CC=C2C(C)(C)CC1 QFPIUBDXPAYMGI-UHFFFAOYSA-N 0.000 claims 1
- 125000004562 2,3-dihydroindol-1-yl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
- 208000004476 Acute Coronary Syndrome Diseases 0.000 claims 1
- 206010002388 Angina unstable Diseases 0.000 claims 1
- 200000000007 Arterial disease Diseases 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- 206010008088 Cerebral artery embolism Diseases 0.000 claims 1
- 206010008092 Cerebral artery thrombosis Diseases 0.000 claims 1
- 206010011091 Coronary artery thrombosis Diseases 0.000 claims 1
- 206010051055 Deep vein thrombosis Diseases 0.000 claims 1
- 206010014513 Embolism arterial Diseases 0.000 claims 1
- 206010037379 Pulmonary embolism and thrombosis Diseases 0.000 claims 1
- 206010063544 Renal embolism Diseases 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 claims 1
- 206010042434 Sudden death Diseases 0.000 claims 1
- 208000007536 Thrombosis Diseases 0.000 claims 1
- 208000032109 Transient ischaemic attack Diseases 0.000 claims 1
- 208000007814 Unstable Angina Diseases 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 claims 1
- 210000005242 cardiac chamber Anatomy 0.000 claims 1
- 230000002612 cardiopulmonary effect Effects 0.000 claims 1
- 208000002528 coronary thrombosis Diseases 0.000 claims 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000001631 haemodialysis Methods 0.000 claims 1
- 230000000322 hemodialysis Effects 0.000 claims 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 1
- 239000007943 implant Substances 0.000 claims 1
- 125000001041 indolyl group Chemical group 0.000 claims 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims 1
- 201000010849 intracranial embolism Diseases 0.000 claims 1
- 230000000302 ischemic effect Effects 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- LFFKWOOHLNFMKG-UHFFFAOYSA-N methyl 1-[3-[[4-(trifluoromethoxy)phenyl]carbamoylamino]pyridin-2-yl]indole-3-carboxylate Chemical compound C12=CC=CC=C2C(C(=O)OC)=CN1C1=NC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 LFFKWOOHLNFMKG-UHFFFAOYSA-N 0.000 claims 1
- XCKBVSLQEPNBRT-UHFFFAOYSA-N methyl 1-[3-[[4-(trifluoromethoxy)phenyl]carbamoylamino]pyridin-2-yl]indole-4-carboxylate Chemical compound C1=CC=2C(C(=O)OC)=CC=CC=2N1C1=NC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 XCKBVSLQEPNBRT-UHFFFAOYSA-N 0.000 claims 1
- OWYBGZLTKSVVKX-UHFFFAOYSA-N methyl 2-[1-[2-[[4-(trifluoromethoxy)phenyl]carbamoylamino]phenyl]indol-3-yl]acetate Chemical compound C12=CC=CC=C2C(CC(=O)OC)=CN1C1=CC=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 OWYBGZLTKSVVKX-UHFFFAOYSA-N 0.000 claims 1
- 230000002093 peripheral effect Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 1
- 230000000306 recurrent effect Effects 0.000 claims 1
- UWOLKXCITASVCQ-UHFFFAOYSA-N spiro[indole-3,4'-piperidine]-1'-carboxamide Chemical compound C1CN(C(=O)N)CCC21C1=CC=CC=C1N=C2 UWOLKXCITASVCQ-UHFFFAOYSA-N 0.000 claims 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 125000001113 thiadiazolyl group Chemical group 0.000 claims 1
- 201000005060 thrombophlebitis Diseases 0.000 claims 1
- 201000010875 transient cerebral ischemia Diseases 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 abstract 1
Classifications
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C—CHEMISTRY; METALLURGY
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- 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
- C07D215/04—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
- C07D215/06—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms having only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to the ring nitrogen atom
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
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US57028804P | 2004-05-12 | 2004-05-12 | |
US66573505P | 2005-03-28 | 2005-03-28 | |
US11/126,567 US7550499B2 (en) | 2004-05-12 | 2005-05-10 | Urea antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions |
PCT/US2005/016525 WO2005113537A2 (en) | 2004-05-12 | 2005-05-11 | Urea antagonists of p2y1 receptor useful in the treatment of thrombotic conditions |
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EP (1) | EP1750704B1 (da) |
JP (1) | JP4795336B2 (da) |
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2005
- 2005-05-10 US US11/126,567 patent/US7550499B2/en active Active
- 2005-05-11 PT PT05779448T patent/PT1750704E/pt unknown
- 2005-05-11 PL PL05779448T patent/PL1750704T3/pl unknown
- 2005-05-11 SI SI200530770T patent/SI1750704T1/sl unknown
- 2005-05-11 KR KR1020067023615A patent/KR20070011479A/ko not_active Application Discontinuation
- 2005-05-11 EP EP05779448A patent/EP1750704B1/en active Active
- 2005-05-11 MX MXPA06013024A patent/MXPA06013024A/es active IP Right Grant
- 2005-05-11 AU AU2005245400A patent/AU2005245400A1/en not_active Abandoned
- 2005-05-11 CN CN2005800231306A patent/CN1984655B/zh not_active Expired - Fee Related
- 2005-05-11 WO PCT/US2005/016525 patent/WO2005113537A2/en active Application Filing
- 2005-05-11 JP JP2007513323A patent/JP4795336B2/ja not_active Expired - Fee Related
- 2005-05-11 CN CNA2005800236206A patent/CN1984892A/zh active Pending
- 2005-05-11 DE DE602005015577T patent/DE602005015577D1/de active Active
- 2005-05-11 ES ES05779448T patent/ES2328716T3/es active Active
- 2005-05-11 DK DK05779448T patent/DK1750704T3/da active
-
2006
- 2006-12-01 NO NO20065544A patent/NO20065544L/no not_active Application Discontinuation
-
2009
- 2009-09-03 HR HR20090468T patent/HRP20090468T1/hr unknown
- 2009-10-13 CY CY20091101048T patent/CY1109487T1/el unknown
Also Published As
Publication number | Publication date |
---|---|
AU2005245400A1 (en) | 2005-12-01 |
KR20070011479A (ko) | 2007-01-24 |
EP1750704B1 (en) | 2009-07-22 |
ES2328716T3 (es) | 2009-11-17 |
DE602005015577D1 (de) | 2009-09-03 |
US7550499B2 (en) | 2009-06-23 |
WO2005113537A3 (en) | 2005-12-22 |
WO2005113537A2 (en) | 2005-12-01 |
US20050261244A1 (en) | 2005-11-24 |
CN1984655A (zh) | 2007-06-20 |
PL1750704T3 (pl) | 2010-01-29 |
MXPA06013024A (es) | 2006-12-20 |
JP4795336B2 (ja) | 2011-10-19 |
PT1750704E (pt) | 2009-10-06 |
EP1750704A2 (en) | 2007-02-14 |
CN1984655B (zh) | 2011-11-30 |
JP2007537273A (ja) | 2007-12-20 |
CN1984892A (zh) | 2007-06-20 |
SI1750704T1 (sl) | 2009-12-31 |
DK1750704T3 (da) | 2009-11-02 |
NO20065544L (no) | 2006-12-05 |
CY1109487T1 (el) | 2012-05-23 |
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