RU2647727C2 - Производные бензо[1,3]диоксина и их применение в качестве lpar5 антагонистов - Google Patents
Производные бензо[1,3]диоксина и их применение в качестве lpar5 антагонистов Download PDFInfo
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- RU2647727C2 RU2647727C2 RU2014151240A RU2014151240A RU2647727C2 RU 2647727 C2 RU2647727 C2 RU 2647727C2 RU 2014151240 A RU2014151240 A RU 2014151240A RU 2014151240 A RU2014151240 A RU 2014151240A RU 2647727 C2 RU2647727 C2 RU 2647727C2
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- RU
- Russia
- Prior art keywords
- dioxin
- alkyl
- benzo
- carboxylic acid
- group
- Prior art date
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- 239000005557 antagonist Substances 0.000 title abstract description 9
- TWSIYGATPWEKBK-UHFFFAOYSA-N 4h-1,3-benzodioxine Chemical class C1=CC=C2OCOCC2=C1 TWSIYGATPWEKBK-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 234
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 114
- 125000001424 substituent group Chemical group 0.000 claims abstract description 87
- 101001038037 Homo sapiens Lysophosphatidic acid receptor 5 Proteins 0.000 claims abstract description 61
- 150000003839 salts Chemical class 0.000 claims abstract description 61
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 57
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 50
- 239000001257 hydrogen Substances 0.000 claims abstract description 49
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 49
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 48
- 150000002367 halogens Chemical class 0.000 claims abstract description 48
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 46
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 39
- 210000003630 histaminocyte Anatomy 0.000 claims abstract description 39
- 239000011737 fluorine Substances 0.000 claims abstract description 35
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 35
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 32
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 31
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 31
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 30
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 29
- 238000011282 treatment Methods 0.000 claims abstract description 29
- 230000004913 activation Effects 0.000 claims abstract description 27
- 210000000274 microglia Anatomy 0.000 claims abstract description 25
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims abstract description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 23
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims abstract description 22
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 21
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 20
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 18
- 125000003118 aryl group Chemical group 0.000 claims abstract description 15
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 15
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims abstract description 14
- WETJKOLTAUGJRY-UHFFFAOYSA-N 6-chloro-4,4-dicyclohexyl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=C(Cl)C=C2C1(C1CCCCC1)C1CCCCC1 WETJKOLTAUGJRY-UHFFFAOYSA-N 0.000 claims abstract description 9
- AVMYLGNHPBELGC-UHFFFAOYSA-N 6-chloro-4-cyclohexyl-4-phenyl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=C(Cl)C=C2C1(C=1C=CC=CC=1)C1CCCCC1 AVMYLGNHPBELGC-UHFFFAOYSA-N 0.000 claims abstract description 9
- 208000001435 Thromboembolism Diseases 0.000 claims abstract description 9
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 8
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 7
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims abstract description 5
- 150000001924 cycloalkanes Chemical class 0.000 claims abstract description 5
- -1 pyridinyl-O- Chemical class 0.000 claims description 33
- 230000015572 biosynthetic process Effects 0.000 claims description 23
- 230000005764 inhibitory process Effects 0.000 claims description 22
- 201000010099 disease Diseases 0.000 claims description 20
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 20
- 208000007536 Thrombosis Diseases 0.000 claims description 19
- 238000002560 therapeutic procedure Methods 0.000 claims description 18
- 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 description 13
- 230000020411 cell activation Effects 0.000 claims description 9
- 208000006011 Stroke Diseases 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000002757 morpholinyl group Chemical group 0.000 claims description 8
- 208000005189 Embolism Diseases 0.000 claims description 7
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- KDKJWPODDXVGNR-UHFFFAOYSA-N 6-bromo-4,4-dicyclohexyl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=C(Br)C=C2C1(C1CCCCC1)C1CCCCC1 KDKJWPODDXVGNR-UHFFFAOYSA-N 0.000 claims description 6
- 206010000891 acute myocardial infarction Diseases 0.000 claims description 6
- 230000033115 angiogenesis Effects 0.000 claims description 6
- 201000006417 multiple sclerosis Diseases 0.000 claims description 6
- 230000001575 pathological effect Effects 0.000 claims description 6
- 208000037803 restenosis Diseases 0.000 claims description 6
- 230000001052 transient effect Effects 0.000 claims description 6
- 208000004454 Hyperalgesia Diseases 0.000 claims description 5
- 208000035154 Hyperesthesia Diseases 0.000 claims description 5
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 5
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
- 230000002792 vascular Effects 0.000 claims description 5
- WKCGQNXDJFNFQP-UHFFFAOYSA-N 3-(6-chloro-4,4-dicyclohexyl-1,3-benzodioxin-2-yl)-2h-1,2,4-oxadiazol-5-one Chemical compound C12=CC(Cl)=CC=C2OC(C=2NOC(=O)N=2)OC1(C1CCCCC1)C1CCCCC1 WKCGQNXDJFNFQP-UHFFFAOYSA-N 0.000 claims description 4
- DBQKLTSTMBXCTA-UHFFFAOYSA-N 4,4-dicyclohexyl-7-pyrrol-1-yl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC(N3C=CC=C3)=CC=C2C1(C1CCCCC1)C1CCCCC1 DBQKLTSTMBXCTA-UHFFFAOYSA-N 0.000 claims description 4
- ICDZRZKGMHSATO-UHFFFAOYSA-N 4h-1,3-benzodioxine-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)OCC2=C1 ICDZRZKGMHSATO-UHFFFAOYSA-N 0.000 claims description 4
- DZTYTOKNBZNHIB-UHFFFAOYSA-N 5-(6-chloro-4,4-dicyclohexyl-1,3-benzodioxin-2-yl)-2h-tetrazole Chemical compound C12=CC(Cl)=CC=C2OC(C2=NNN=N2)OC1(C1CCCCC1)C1CCCCC1 DZTYTOKNBZNHIB-UHFFFAOYSA-N 0.000 claims description 4
- DHKAHPFOIXOWHE-UHFFFAOYSA-N 5-(6-chloro-4,4-dicyclohexyl-1,3-benzodioxin-2-yl)-3h-1,3,4-oxadiazol-2-one Chemical compound C12=CC(Cl)=CC=C2OC(C=2OC(=O)NN=2)OC1(C1CCCCC1)C1CCCCC1 DHKAHPFOIXOWHE-UHFFFAOYSA-N 0.000 claims description 4
- 206010008092 Cerebral artery thrombosis Diseases 0.000 claims description 4
- 206010011091 Coronary artery thrombosis Diseases 0.000 claims description 4
- 206010051055 Deep vein thrombosis Diseases 0.000 claims description 4
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 4
- 206010063544 Renal embolism Diseases 0.000 claims description 4
- 206010047249 Venous thrombosis Diseases 0.000 claims description 4
- 238000007887 coronary angioplasty Methods 0.000 claims description 4
- 208000002528 coronary thrombosis Diseases 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 201000011461 pre-eclampsia Diseases 0.000 claims description 4
- 201000005060 thrombophlebitis Diseases 0.000 claims description 4
- CGKINPBJKARFLP-UHFFFAOYSA-N 1,1-dicyclohexyl-7,8,9,10-tetrahydrobenzo[f][1,3]benzodioxine-3-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=C3CCCCC3=C2C1(C1CCCCC1)C1CCCCC1 CGKINPBJKARFLP-UHFFFAOYSA-N 0.000 claims description 3
- LWZJFTCOUTZELF-UHFFFAOYSA-N 1,1-dicyclohexylbenzo[f][1,3]benzodioxine-3-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=C3C=CC=CC3=C2C1(C1CCCCC1)C1CCCCC1 LWZJFTCOUTZELF-UHFFFAOYSA-N 0.000 claims description 3
- YUCIBCCPUGNTDT-UHFFFAOYSA-N 10-benzyl-4,4-dicyclohexylbenzo[g][1,3]benzodioxine-2-carboxylic acid Chemical compound C12=CC=CC=C2C=C2C(C3CCCCC3)(C3CCCCC3)OC(C(=O)O)OC2=C1CC1=CC=CC=C1 YUCIBCCPUGNTDT-UHFFFAOYSA-N 0.000 claims description 3
- WAXRDOOISKVDOT-UHFFFAOYSA-N 4,4-di(cycloheptyl)-6-(trifluoromethoxy)-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=C(OC(F)(F)F)C=C2C1(C1CCCCCC1)C1CCCCCC1 WAXRDOOISKVDOT-UHFFFAOYSA-N 0.000 claims description 3
- MBUCGUYVKGSEHA-UHFFFAOYSA-N 4,4-dicyclohexyl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=CC=C2C1(C1CCCCC1)C1CCCCC1 MBUCGUYVKGSEHA-UHFFFAOYSA-N 0.000 claims description 3
- JOJGLFXLBYZKGB-UHFFFAOYSA-N 4,4-dicyclohexyl-5,7-difluoro-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC(F)=CC(F)=C2C1(C1CCCCC1)C1CCCCC1 JOJGLFXLBYZKGB-UHFFFAOYSA-N 0.000 claims description 3
- YBMFWFCVTOAMTR-UHFFFAOYSA-N 4,4-dicyclohexyl-5,7-dimethoxy-1,3-benzodioxine-2-carboxylic acid Chemical compound C=1C(OC)=CC(OC)=C2C=1OC(C(O)=O)OC2(C1CCCCC1)C1CCCCC1 YBMFWFCVTOAMTR-UHFFFAOYSA-N 0.000 claims description 3
- PVUPGOUGVPNXRU-UHFFFAOYSA-N 4,4-dicyclohexyl-5-ethoxy-1,3-benzodioxine-2-carboxylic acid Chemical compound C1=2C(OCC)=CC=CC=2OC(C(O)=O)OC1(C1CCCCC1)C1CCCCC1 PVUPGOUGVPNXRU-UHFFFAOYSA-N 0.000 claims description 3
- QDVMDMANAAENOD-UHFFFAOYSA-N 4,4-dicyclohexyl-5-methyl-1,3-benzodioxine-2-carboxylic acid Chemical compound C1=2C(C)=CC=CC=2OC(C(O)=O)OC1(C1CCCCC1)C1CCCCC1 QDVMDMANAAENOD-UHFFFAOYSA-N 0.000 claims description 3
- LMYZHOYELPVYPT-UHFFFAOYSA-N 4,4-dicyclohexyl-6-(3-methoxyphenoxy)-1,3-benzodioxine-2-carboxylic acid Chemical compound COC1=CC=CC(OC=2C=C3C(C4CCCCC4)(C4CCCCC4)OC(OC3=CC=2)C(O)=O)=C1 LMYZHOYELPVYPT-UHFFFAOYSA-N 0.000 claims description 3
- OJZKUQVZXKOGDE-UHFFFAOYSA-N 4,4-dicyclohexyl-6-(trifluoromethoxy)-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=C(OC(F)(F)F)C=C2C1(C1CCCCC1)C1CCCCC1 OJZKUQVZXKOGDE-UHFFFAOYSA-N 0.000 claims description 3
- ZOLCCSWVSQMFBG-UHFFFAOYSA-N 4,4-dicyclohexyl-6-(trifluoromethyl)-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=C(C(F)(F)F)C=C2C1(C1CCCCC1)C1CCCCC1 ZOLCCSWVSQMFBG-UHFFFAOYSA-N 0.000 claims description 3
- JUGCDSDJNBWLJX-UHFFFAOYSA-N 4,4-dicyclohexyl-6-fluoro-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=C(F)C=C2C1(C1CCCCC1)C1CCCCC1 JUGCDSDJNBWLJX-UHFFFAOYSA-N 0.000 claims description 3
- UNPSUVUWCYRLAV-UHFFFAOYSA-N 4,4-dicyclohexyl-6-iodo-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=C(I)C=C2C1(C1CCCCC1)C1CCCCC1 UNPSUVUWCYRLAV-UHFFFAOYSA-N 0.000 claims description 3
- APFALXFHUMONES-UHFFFAOYSA-N 4,4-dicyclohexyl-6-methoxy-1,3-benzodioxine-2-carboxylic acid Chemical compound C12=CC(OC)=CC=C2OC(C(O)=O)OC1(C1CCCCC1)C1CCCCC1 APFALXFHUMONES-UHFFFAOYSA-N 0.000 claims description 3
- UYEBYMXVPXATKI-UHFFFAOYSA-N 4,4-dicyclohexyl-6-phenyl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=C(C=3C=CC=CC=3)C=C2C1(C1CCCCC1)C1CCCCC1 UYEBYMXVPXATKI-UHFFFAOYSA-N 0.000 claims description 3
- VUGKJOIJENCQHI-UHFFFAOYSA-N 4,4-dicyclohexyl-6-pyridin-3-yloxy-1,3-benzodioxine-2-carboxylic acid Chemical compound C1=C2C(C3CCCCC3)(C3CCCCC3)OC(C(=O)O)OC2=CC=C1OC1=CC=CN=C1 VUGKJOIJENCQHI-UHFFFAOYSA-N 0.000 claims description 3
- QAOMCUWIGZSPHK-UHFFFAOYSA-N 4,4-dicyclohexyl-6-pyridin-4-yl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=C(C=3C=CN=CC=3)C=C2C1(C1CCCCC1)C1CCCCC1 QAOMCUWIGZSPHK-UHFFFAOYSA-N 0.000 claims description 3
- PQKIXWFIZHKPGF-UHFFFAOYSA-N 4,4-dicyclohexyl-6-pyrrolidin-1-ylsulfonyl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=C(S(=O)(=O)N3CCCC3)C=C2C1(C1CCCCC1)C1CCCCC1 PQKIXWFIZHKPGF-UHFFFAOYSA-N 0.000 claims description 3
- ZTMLYBVFVDTKGY-UHFFFAOYSA-N 4,4-dicyclohexyl-7-(diethylamino)-1,3-benzodioxine-2-carboxylic acid Chemical compound C=1C(N(CC)CC)=CC=C2C=1OC(C(O)=O)OC2(C1CCCCC1)C1CCCCC1 ZTMLYBVFVDTKGY-UHFFFAOYSA-N 0.000 claims description 3
- ISFWOCTVLCBYSR-UHFFFAOYSA-N 4,4-dicyclohexyl-7-(dimethylamino)-1,3-benzodioxine-2-carboxylic acid Chemical compound C=1C(N(C)C)=CC=C2C=1OC(C(O)=O)OC2(C1CCCCC1)C1CCCCC1 ISFWOCTVLCBYSR-UHFFFAOYSA-N 0.000 claims description 3
- ZYHRODKZKDHELH-UHFFFAOYSA-N 4,4-dicyclohexyl-7-methoxy-1,3-benzodioxine-2-carboxylic acid Chemical compound C=1C(OC)=CC=C2C=1OC(C(O)=O)OC2(C1CCCCC1)C1CCCCC1 ZYHRODKZKDHELH-UHFFFAOYSA-N 0.000 claims description 3
- CBGGTXULLJKPGU-UHFFFAOYSA-N 4,4-dicyclohexyl-7-methoxy-5-methyl-1,3-benzodioxine-2-carboxylic acid Chemical compound C=1C(OC)=CC(C)=C2C=1OC(C(O)=O)OC2(C1CCCCC1)C1CCCCC1 CBGGTXULLJKPGU-UHFFFAOYSA-N 0.000 claims description 3
- ROUBXFAVLIQQFT-UHFFFAOYSA-N 4,4-dicyclohexyl-7-methyl-1,3-benzodioxine-2-carboxylic acid Chemical compound C=1C(C)=CC=C2C=1OC(C(O)=O)OC2(C1CCCCC1)C1CCCCC1 ROUBXFAVLIQQFT-UHFFFAOYSA-N 0.000 claims description 3
- VLPQUKUASDWSKS-UHFFFAOYSA-N 4,4-dicyclohexyl-7-morpholin-4-yl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC(N3CCOCC3)=CC=C2C1(C1CCCCC1)C1CCCCC1 VLPQUKUASDWSKS-UHFFFAOYSA-N 0.000 claims description 3
- JQUBLGPIULPKCS-UHFFFAOYSA-N 4,4-dicyclohexyl-7-phenylmethoxy-1,3-benzodioxine-2-carboxylic acid Chemical compound C=1C=C2C(C3CCCCC3)(C3CCCCC3)OC(C(=O)O)OC2=CC=1OCC1=CC=CC=C1 JQUBLGPIULPKCS-UHFFFAOYSA-N 0.000 claims description 3
- WYEOQDHXVWKTDD-UHFFFAOYSA-N 4,4-dicyclohexyl-8-(trifluoromethoxy)-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=C(OC(F)(F)F)C=CC=C2C1(C1CCCCC1)C1CCCCC1 WYEOQDHXVWKTDD-UHFFFAOYSA-N 0.000 claims description 3
- NTAQXGSXPPBJFK-UHFFFAOYSA-N 4,4-dicyclohexyl-8-fluoro-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=C(F)C=CC=C2C1(C1CCCCC1)C1CCCCC1 NTAQXGSXPPBJFK-UHFFFAOYSA-N 0.000 claims description 3
- IXDXBIUPFXTVBB-UHFFFAOYSA-N 4,4-dicyclohexyl-8-methoxy-1,3-benzodioxine-2-carboxylic acid Chemical compound COC1=CC=CC2=C1OC(C(O)=O)OC2(C1CCCCC1)C1CCCCC1 IXDXBIUPFXTVBB-UHFFFAOYSA-N 0.000 claims description 3
- YFKGJAVKSKZPSC-UHFFFAOYSA-N 4,4-dicyclohexyl-8-methyl-1,3-benzodioxine-2-carboxylic acid Chemical compound CC1=CC=CC2=C1OC(C(O)=O)OC2(C1CCCCC1)C1CCCCC1 YFKGJAVKSKZPSC-UHFFFAOYSA-N 0.000 claims description 3
- CNOGCZUOGVSHQT-UHFFFAOYSA-N 4,4-dicyclohexylbenzo[g][1,3]benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC3=CC=CC=C3C=C2C1(C1CCCCC1)C1CCCCC1 CNOGCZUOGVSHQT-UHFFFAOYSA-N 0.000 claims description 3
- FXMWJGVQPHEEHB-UHFFFAOYSA-N 4,4-dicyclohexylbenzo[h][1,3]benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC(C2=CC=CC=C2C=C2)=C2C1(C1CCCCC1)C1CCCCC1 FXMWJGVQPHEEHB-UHFFFAOYSA-N 0.000 claims description 3
- QIFNMQAHOULZJM-UHFFFAOYSA-N 6,8-dichloro-4,4-dicyclohexyl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=C(Cl)C=C(Cl)C=C2C1(C1CCCCC1)C1CCCCC1 QIFNMQAHOULZJM-UHFFFAOYSA-N 0.000 claims description 3
- NRWJQWMWMQRUNW-UHFFFAOYSA-N 6-(3-chlorophenoxy)-4,4-dicyclohexyl-1,3-benzodioxine-2-carboxylic acid Chemical compound C1=C2C(C3CCCCC3)(C3CCCCC3)OC(C(=O)O)OC2=CC=C1OC1=CC=CC(Cl)=C1 NRWJQWMWMQRUNW-UHFFFAOYSA-N 0.000 claims description 3
- SMIDBSMNWLETBS-UHFFFAOYSA-N 6-(4-chlorobenzoyl)-4,4-dicyclohexyl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=C(C(=O)C=3C=CC(Cl)=CC=3)C=C2C1(C1CCCCC1)C1CCCCC1 SMIDBSMNWLETBS-UHFFFAOYSA-N 0.000 claims description 3
- TWDRWHNYDGJARY-UHFFFAOYSA-N 6-(4-chlorophenoxy)-4,4-dicyclohexyl-1,3-benzodioxine-2-carboxylic acid Chemical compound C1=C2C(C3CCCCC3)(C3CCCCC3)OC(C(=O)O)OC2=CC=C1OC1=CC=C(Cl)C=C1 TWDRWHNYDGJARY-UHFFFAOYSA-N 0.000 claims description 3
- MEVCCTSZUVOZOO-UHFFFAOYSA-N 6-bromo-4,4-di(cycloheptyl)-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=C(Br)C=C2C1(C1CCCCCC1)C1CCCCCC1 MEVCCTSZUVOZOO-UHFFFAOYSA-N 0.000 claims description 3
- JLDUWYSFYXJSOJ-UHFFFAOYSA-N 6-chloro-4,4-di(cycloheptyl)-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=C(Cl)C=C2C1(C1CCCCCC1)C1CCCCCC1 JLDUWYSFYXJSOJ-UHFFFAOYSA-N 0.000 claims description 3
- MIJGJCGTZZGABX-UHFFFAOYSA-N 6-chloro-4,4-di(cycloheptyl)-7-methyl-1,3-benzodioxine-2-carboxylic acid Chemical compound C1=2C=C(Cl)C(C)=CC=2OC(C(O)=O)OC1(C1CCCCCC1)C1CCCCCC1 MIJGJCGTZZGABX-UHFFFAOYSA-N 0.000 claims description 3
- PSQPVSZHYMTKTM-UHFFFAOYSA-N 6-chloro-4,4-di(cyclooctyl)-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=C(Cl)C=C2C1(C1CCCCCCC1)C1CCCCCCC1 PSQPVSZHYMTKTM-UHFFFAOYSA-N 0.000 claims description 3
- KOLNJYAVUKRGBP-UHFFFAOYSA-N 6-chloro-4,4-dicyclohexyl-2-methyl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C)(C(O)=O)OC2=CC=C(Cl)C=C2C1(C1CCCCC1)C1CCCCC1 KOLNJYAVUKRGBP-UHFFFAOYSA-N 0.000 claims description 3
- UNRMFSCCXVRPDR-UHFFFAOYSA-N 6-chloro-4,4-dicyclohexyl-5-fluoro-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=C(Cl)C(F)=C2C1(C1CCCCC1)C1CCCCC1 UNRMFSCCXVRPDR-UHFFFAOYSA-N 0.000 claims description 3
- NQYVUFAEKZROKZ-UHFFFAOYSA-N 6-chloro-4,4-dicyclohexyl-7-fluoro-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC(F)=C(Cl)C=C2C1(C1CCCCC1)C1CCCCC1 NQYVUFAEKZROKZ-UHFFFAOYSA-N 0.000 claims description 3
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
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- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12305553.5 | 2012-05-18 | ||
| EP12305553 | 2012-05-18 | ||
| PCT/EP2013/060172 WO2013171318A1 (en) | 2012-05-18 | 2013-05-16 | Benzo[1,3]dioxine derivatives and their use as lpar5 antagonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2014151240A RU2014151240A (ru) | 2016-07-10 |
| RU2647727C2 true RU2647727C2 (ru) | 2018-03-19 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2014151240A RU2647727C2 (ru) | 2012-05-18 | 2013-05-16 | Производные бензо[1,3]диоксина и их применение в качестве lpar5 антагонистов |
Country Status (16)
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| EP (1) | EP2850070B1 (enExample) |
| JP (1) | JP6238970B2 (enExample) |
| KR (1) | KR20150016304A (enExample) |
| CN (1) | CN104302633B (enExample) |
| AU (1) | AU2013261719B2 (enExample) |
| BR (1) | BR112014028189A2 (enExample) |
| CA (1) | CA2871545A1 (enExample) |
| ES (1) | ES2649438T3 (enExample) |
| IL (1) | IL235219A (enExample) |
| MX (1) | MX354521B (enExample) |
| PL (1) | PL2850070T3 (enExample) |
| RU (1) | RU2647727C2 (enExample) |
| SG (1) | SG11201407216YA (enExample) |
| SI (1) | SI2850070T1 (enExample) |
| WO (1) | WO2013171318A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US20200215085A1 (en) * | 2017-07-19 | 2020-07-09 | Uti Limited Partnership | Method to Abate Acute Airway Hypersensitivity and Asthma Attacks |
| KR20250140741A (ko) | 2024-03-19 | 2025-09-26 | 경북대학교 산학협력단 | 알룰로스를 포함하는 혈전 예방 또는 개선용 조성물 및 이의 이용 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2022579A (en) * | 1978-05-03 | 1979-12-19 | Roussel Uclaf | 4h-1,3-benzodioxin-2-carboxylic acid derivatives |
| SU1277893A3 (ru) * | 1982-05-12 | 1986-12-15 | Империал Кемикал Индастриз,Плс (Фирма) | Способ получени производных 4-фенил-1,3-диоксан-цис-5-илалкеновой кислоты или их оптически активных форм,или их физиологически приемлемых солей с основани ми |
| WO2005000284A2 (en) * | 2003-05-20 | 2005-01-06 | Bayer Pharmaceuticals Corporation | Diaryl ureas for diseases mediated by pdgfr |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4056540A (en) | 1974-01-01 | 1977-11-01 | Bristol-Myers Company | 4-Phenyl-1,3-benzodioxans |
| US4056450A (en) | 1975-06-30 | 1977-11-01 | M & T Chemicals Inc. | Continuous detinning system |
| FR2424914A2 (fr) * | 1978-05-03 | 1979-11-30 | Roussel Uclaf | Nouveaux derives de (1-3) benzodioxine, un procede pour leur preparation et leur application comme medicaments |
| FR2704857B1 (fr) * | 1993-05-07 | 1995-06-23 | Adir | Nouvelles benzodioxines substituées, leur procédé de préparation et les compositions pharmaceutiques les contenant. |
| CN101124226A (zh) * | 2004-05-07 | 2008-02-13 | 记忆药物公司 | 1h-吲唑、苯并噻唑、1,2-苯并异噁唑、1,2-苯并异噻唑和色酮以及它们的制备和用途 |
| WO2010042600A2 (en) * | 2008-10-08 | 2010-04-15 | The Uab Research Foundation | Photo-activatable therapeutic agents and methods of using |
-
2013
- 2013-05-16 SG SG11201407216YA patent/SG11201407216YA/en unknown
- 2013-05-16 BR BR112014028189A patent/BR112014028189A2/pt not_active Application Discontinuation
- 2013-05-16 PL PL13723767T patent/PL2850070T3/pl unknown
- 2013-05-16 MX MX2014014012A patent/MX354521B/es active IP Right Grant
- 2013-05-16 WO PCT/EP2013/060172 patent/WO2013171318A1/en not_active Ceased
- 2013-05-16 RU RU2014151240A patent/RU2647727C2/ru not_active IP Right Cessation
- 2013-05-16 AU AU2013261719A patent/AU2013261719B2/en not_active Ceased
- 2013-05-16 SI SI201330853T patent/SI2850070T1/en unknown
- 2013-05-16 EP EP13723767.3A patent/EP2850070B1/en not_active Not-in-force
- 2013-05-16 CN CN201380025938.2A patent/CN104302633B/zh not_active Expired - Fee Related
- 2013-05-16 KR KR20147033844A patent/KR20150016304A/ko not_active Withdrawn
- 2013-05-16 ES ES13723767.3T patent/ES2649438T3/es active Active
- 2013-05-16 CA CA 2871545 patent/CA2871545A1/en not_active Abandoned
- 2013-05-16 US US14/401,041 patent/US9221784B2/en not_active Expired - Fee Related
- 2013-05-16 JP JP2015512073A patent/JP6238970B2/ja not_active Expired - Fee Related
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2014
- 2014-10-20 IL IL235219A patent/IL235219A/en active IP Right Grant
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2022579A (en) * | 1978-05-03 | 1979-12-19 | Roussel Uclaf | 4h-1,3-benzodioxin-2-carboxylic acid derivatives |
| SU1277893A3 (ru) * | 1982-05-12 | 1986-12-15 | Империал Кемикал Индастриз,Плс (Фирма) | Способ получени производных 4-фенил-1,3-диоксан-цис-5-илалкеновой кислоты или их оптически активных форм,или их физиологически приемлемых солей с основани ми |
| WO2005000284A2 (en) * | 2003-05-20 | 2005-01-06 | Bayer Pharmaceuticals Corporation | Diaryl ureas for diseases mediated by pdgfr |
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| John F.Gilmer et al. "Synthesis, hydrolysis kinetics and anti- platelet effects of isosoride mononitrate derivatives of aspirin", European J. of Pharmaceutical Seinces, 2001, v. 14, no. 3, p. 221-227. * |
Also Published As
| Publication number | Publication date |
|---|---|
| IL235219A (en) | 2017-03-30 |
| EP2850070B1 (en) | 2017-08-23 |
| KR20150016304A (ko) | 2015-02-11 |
| RU2014151240A (ru) | 2016-07-10 |
| BR112014028189A2 (pt) | 2017-06-27 |
| MX354521B (es) | 2018-03-08 |
| AU2013261719A1 (en) | 2014-12-18 |
| ES2649438T3 (es) | 2018-01-12 |
| WO2013171318A1 (en) | 2013-11-21 |
| MX2014014012A (es) | 2015-02-12 |
| CN104302633B (zh) | 2016-09-07 |
| SI2850070T1 (en) | 2018-01-31 |
| CA2871545A1 (en) | 2013-11-21 |
| SG11201407216YA (en) | 2014-12-30 |
| PL2850070T3 (pl) | 2018-01-31 |
| JP2015517515A (ja) | 2015-06-22 |
| AU2013261719B2 (en) | 2017-07-27 |
| US20150111889A1 (en) | 2015-04-23 |
| CN104302633A (zh) | 2015-01-21 |
| EP2850070A1 (en) | 2015-03-25 |
| JP6238970B2 (ja) | 2017-11-29 |
| US9221784B2 (en) | 2015-12-29 |
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| MM4A | The patent is invalid due to non-payment of fees |
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