ES2649438T3 - Derivados de benzo[1,3]dioxina y su uso como antagonistas de LPAR5 - Google Patents
Derivados de benzo[1,3]dioxina y su uso como antagonistas de LPAR5 Download PDFInfo
- Publication number
- ES2649438T3 ES2649438T3 ES13723767.3T ES13723767T ES2649438T3 ES 2649438 T3 ES2649438 T3 ES 2649438T3 ES 13723767 T ES13723767 T ES 13723767T ES 2649438 T3 ES2649438 T3 ES 2649438T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- dioxin
- benzo
- series consisting
- carboxylic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 101001038037 Homo sapiens Lysophosphatidic acid receptor 5 Proteins 0.000 title claims description 57
- 102100040404 Lysophosphatidic acid receptor 5 Human genes 0.000 title description 31
- 239000005557 antagonist Substances 0.000 title description 8
- TWSIYGATPWEKBK-UHFFFAOYSA-N 4h-1,3-benzodioxine Chemical class C1=CC=C2OCOCC2=C1 TWSIYGATPWEKBK-UHFFFAOYSA-N 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 224
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 96
- 125000001424 substituent group Chemical group 0.000 claims abstract description 84
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 83
- 150000003839 salts Chemical class 0.000 claims abstract description 65
- 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 55
- 150000002367 halogens Chemical class 0.000 claims abstract description 52
- 239000001257 hydrogen Substances 0.000 claims abstract description 51
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 51
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 49
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 43
- 239000011737 fluorine Substances 0.000 claims abstract description 42
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 39
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 37
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 36
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 35
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 33
- -1 cyclohexyl-4-phenyl-4H-benzo [1,3] dioxin-2-carboxylic acid Chemical compound 0.000 claims abstract description 33
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 33
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 31
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims abstract description 27
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 26
- 239000002253 acid Substances 0.000 claims abstract description 25
- 239000000203 mixture Substances 0.000 claims abstract description 23
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 21
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 20
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 19
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 18
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 17
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 17
- 125000003118 aryl group Chemical group 0.000 claims abstract description 16
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 10
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims abstract description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 9
- 150000001924 cycloalkanes Chemical class 0.000 claims abstract description 8
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 8
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims abstract description 5
- 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 5
- 125000004429 atom Chemical group 0.000 claims abstract description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 3
- 150000002431 hydrogen Chemical class 0.000 claims abstract 5
- 210000003630 histaminocyte Anatomy 0.000 claims description 38
- 230000015572 biosynthetic process Effects 0.000 claims description 33
- 230000005764 inhibitory process Effects 0.000 claims description 28
- 238000011282 treatment Methods 0.000 claims description 27
- 230000009467 reduction Effects 0.000 claims description 26
- 210000000274 microglia Anatomy 0.000 claims description 25
- 238000002560 therapeutic procedure Methods 0.000 claims description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
- 201000010099 disease Diseases 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
- LXOHISCRPIDIIG-UHFFFAOYSA-N 1,4-dioxine-2-carboxylic acid Chemical compound OC(=O)C1=COC=CO1 LXOHISCRPIDIIG-UHFFFAOYSA-N 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 208000007536 Thrombosis Diseases 0.000 claims description 15
- 230000020411 cell activation Effects 0.000 claims description 14
- 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
- 239000003814 drug Substances 0.000 claims description 12
- 230000001575 pathological effect Effects 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 208000037803 restenosis Diseases 0.000 claims description 9
- 125000002757 morpholinyl group Chemical group 0.000 claims description 8
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 7
- 208000001435 Thromboembolism Diseases 0.000 claims description 7
- 230000002776 aggregation Effects 0.000 claims description 7
- 238000004220 aggregation Methods 0.000 claims description 7
- 208000026935 allergic disease Diseases 0.000 claims description 7
- 230000033115 angiogenesis Effects 0.000 claims description 7
- 208000006673 asthma Diseases 0.000 claims description 7
- 201000006417 multiple sclerosis 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
- 208000006011 Stroke Diseases 0.000 claims description 6
- 208000032109 Transient ischaemic attack Diseases 0.000 claims description 6
- 230000001732 thrombotic effect Effects 0.000 claims description 6
- 201000010875 transient cerebral ischemia Diseases 0.000 claims description 6
- 230000002792 vascular Effects 0.000 claims description 6
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 5
- 208000004454 Hyperalgesia Diseases 0.000 claims description 5
- 208000035154 Hyperesthesia Diseases 0.000 claims description 5
- 206010000891 acute myocardial infarction 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
- 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
- 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
- 206010008088 Cerebral artery embolism Diseases 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
- 206010014522 Embolism venous Diseases 0.000 claims description 4
- 206010065390 Inflammatory pain Diseases 0.000 claims description 4
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 4
- 206010037549 Purpura Diseases 0.000 claims description 4
- 241001672981 Purpura Species 0.000 claims description 4
- 206010063544 Renal embolism Diseases 0.000 claims description 4
- 206010047249 Venous thrombosis Diseases 0.000 claims description 4
- 150000001735 carboxylic acids Chemical class 0.000 claims description 4
- 238000007887 coronary angioplasty Methods 0.000 claims description 4
- 208000002528 coronary thrombosis Diseases 0.000 claims description 4
- 208000009190 disseminated intravascular coagulation Diseases 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 201000010849 intracranial embolism Diseases 0.000 claims description 4
- 201000011461 pre-eclampsia Diseases 0.000 claims description 4
- 238000001356 surgical procedure Methods 0.000 claims description 4
- 201000005060 thrombophlebitis Diseases 0.000 claims description 4
- 208000004043 venous thromboembolism 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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 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
- 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
- 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 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
- 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
- KFAZMQCVANACCG-UHFFFAOYSA-N 6-chloro-4,4-dicyclohexyl-7-methyl-1,3-benzodioxine-2-carboxylic acid Chemical compound C1=2C=C(Cl)C(C)=CC=2OC(C(O)=O)OC1(C1CCCCC1)C1CCCCC1 KFAZMQCVANACCG-UHFFFAOYSA-N 0.000 claims description 3
- XKEPFFWGTPYHNI-UHFFFAOYSA-N 6-chloro-4,4-dicyclohexyl-8-methyl-1,3-benzodioxine-2-carboxylic acid Chemical compound CC1=CC(Cl)=CC2=C1OC(C(O)=O)OC2(C1CCCCC1)C1CCCCC1 XKEPFFWGTPYHNI-UHFFFAOYSA-N 0.000 claims description 3
- 206010014513 Embolism arterial Diseases 0.000 claims description 3
- 230000001154 acute effect Effects 0.000 claims description 3
- 210000003462 vein Anatomy 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 2
- 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 2
- 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 2
- 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 2
- 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 2
- DCMVRCLSDLQDJL-UHFFFAOYSA-N 4,4-dicyclohexyl-6-methyl-1,3-benzodioxine-2-carboxylic acid Chemical compound C12=CC(C)=CC=C2OC(C(O)=O)OC1(C1CCCCC1)C1CCCCC1 DCMVRCLSDLQDJL-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 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 2
- 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 2
- 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 2
- 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 2
- 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 2
- 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 2
- 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 2
- 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 2
- 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 2
- 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 2
- ASNFHHPDFMGXNJ-UHFFFAOYSA-N 6-chloro-4,4-dicyclohexyl-8-fluoro-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=C(F)C=C(Cl)C=C2C1(C1CCCCC1)C1CCCCC1 ASNFHHPDFMGXNJ-UHFFFAOYSA-N 0.000 claims description 2
- JVSOMVLADIPVDM-UHFFFAOYSA-N 6-chloro-4,4-dicyclopentyl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC=C(Cl)C=C2C1(C1CCCC1)C1CCCC1 JVSOMVLADIPVDM-UHFFFAOYSA-N 0.000 claims description 2
- OIUMBTSKKUFBAL-UHFFFAOYSA-N 6-chloro-4-cycloheptyl-4h-1,3-benzodioxine-2-carboxylic acid Chemical compound C12=CC(Cl)=CC=C2OC(C(=O)O)OC1C1CCCCCC1 OIUMBTSKKUFBAL-UHFFFAOYSA-N 0.000 claims description 2
- BRJZQGQFLRQVTP-UHFFFAOYSA-N 6-tert-butyl-4,4-dicyclohexyl-1,3-benzodioxine-2-carboxylic acid Chemical compound C12=CC(C(C)(C)C)=CC=C2OC(C(O)=O)OC1(C1CCCCC1)C1CCCCC1 BRJZQGQFLRQVTP-UHFFFAOYSA-N 0.000 claims description 2
- IGUXRXYZDKXFGS-UHFFFAOYSA-N 7-butoxy-4,4-dicyclohexyl-1,3-benzodioxine-2-carboxylic acid Chemical compound C=1C(OCCCC)=CC=C2C=1OC(C(O)=O)OC2(C1CCCCC1)C1CCCCC1 IGUXRXYZDKXFGS-UHFFFAOYSA-N 0.000 claims description 2
- COHDSPLDNUINFU-UHFFFAOYSA-N 8-tert-butyl-4,4-dicyclohexyl-1,3-benzodioxine-2-carboxylic acid Chemical compound CC(C)(C)C1=CC=CC2=C1OC(C(O)=O)OC2(C1CCCCC1)C1CCCCC1 COHDSPLDNUINFU-UHFFFAOYSA-N 0.000 claims description 2
- 208000030939 Chronic inflammatory demyelinating polyneuropathy Diseases 0.000 claims description 2
- 206010053567 Coagulopathies Diseases 0.000 claims description 2
- 208000016192 Demyelinating disease Diseases 0.000 claims description 2
- 208000005189 Embolism Diseases 0.000 claims description 2
- 208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 2
- 206010022562 Intermittent claudication Diseases 0.000 claims description 2
- 206010049567 Miller Fisher syndrome Diseases 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 208000003435 Optic Neuritis Diseases 0.000 claims description 2
- 206010040070 Septic Shock Diseases 0.000 claims description 2
- 208000036142 Viral infection Diseases 0.000 claims description 2
- 230000003187 abdominal effect Effects 0.000 claims description 2
- 230000002159 abnormal effect Effects 0.000 claims description 2
- 239000003146 anticoagulant agent Substances 0.000 claims description 2
- 210000001367 artery Anatomy 0.000 claims description 2
- 208000015294 blood coagulation disease Diseases 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 210000003169 central nervous system Anatomy 0.000 claims description 2
- 201000005795 chronic inflammatory demyelinating polyneuritis Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000001631 haemodialysis Methods 0.000 claims description 2
- 230000000322 hemodialysis Effects 0.000 claims description 2
- 208000021156 intermittent vascular claudication Diseases 0.000 claims description 2
- 210000003127 knee Anatomy 0.000 claims description 2
- 230000007774 longterm Effects 0.000 claims description 2
- 210000003141 lower extremity Anatomy 0.000 claims description 2
- 238000012423 maintenance Methods 0.000 claims description 2
- DEYNIEVZZWOJRQ-UHFFFAOYSA-N methyl 6-chloro-4,4-dicyclohexyl-1,3-benzodioxine-2-carboxylate Chemical compound O1C(C(=O)OC)OC2=CC=C(Cl)C=C2C1(C1CCCCC1)C1CCCCC1 DEYNIEVZZWOJRQ-UHFFFAOYSA-N 0.000 claims description 2
- 208000008795 neuromyelitis optica Diseases 0.000 claims description 2
- 230000002093 peripheral effect Effects 0.000 claims description 2
- 210000001428 peripheral nervous system Anatomy 0.000 claims description 2
- 230000035699 permeability Effects 0.000 claims description 2
- 230000036303 septic shock Effects 0.000 claims description 2
- 230000009885 systemic effect Effects 0.000 claims description 2
- 230000002537 thrombolytic effect Effects 0.000 claims description 2
- 208000009174 transverse myelitis Diseases 0.000 claims description 2
- 238000007891 venous angioplasty Methods 0.000 claims description 2
- 230000009385 viral infection Effects 0.000 claims description 2
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- CSBYNSJIKIGCGU-UHFFFAOYSA-N 7-chloro-4,4-dicyclohexyl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(=O)O)OC2=CC(Cl)=CC=C2C1(C1CCCCC1)C1CCCCC1 CSBYNSJIKIGCGU-UHFFFAOYSA-N 0.000 claims 1
- 208000029067 Neuromyelitis optica spectrum disease Diseases 0.000 claims 1
- 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 abstract description 7
- 150000004702 methyl esters Chemical class 0.000 abstract description 3
- 238000000034 method Methods 0.000 description 46
- 239000000651 prodrug Substances 0.000 description 40
- 229940002612 prodrug Drugs 0.000 description 40
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 35
- 210000001772 blood platelet Anatomy 0.000 description 35
- XGRLSUFHELJJAB-JGSYTFBMSA-M sodium;[(2r)-2-hydroxy-3-[(z)-octadec-9-enoyl]oxypropyl] hydrogen phosphate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)COP(O)([O-])=O XGRLSUFHELJJAB-JGSYTFBMSA-M 0.000 description 35
- 239000000243 solution Substances 0.000 description 32
- 210000004027 cell Anatomy 0.000 description 30
- 230000004913 activation Effects 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 23
- 230000000694 effects Effects 0.000 description 23
- 238000006722 reduction reaction Methods 0.000 description 23
- 238000003786 synthesis reaction Methods 0.000 description 23
- 238000011321 prophylaxis Methods 0.000 description 21
- 238000012360 testing method Methods 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 19
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 230000002401 inhibitory effect Effects 0.000 description 15
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 238000003556 assay Methods 0.000 description 13
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical class C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 13
- 102000004137 Lysophosphatidic Acid Receptors Human genes 0.000 description 12
- 108090000642 Lysophosphatidic Acid Receptors Proteins 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 239000000872 buffer Substances 0.000 description 11
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 125000000524 functional group Chemical group 0.000 description 10
- 230000001404 mediated effect Effects 0.000 description 10
- 239000012071 phase Substances 0.000 description 10
- 239000002243 precursor Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 235000019439 ethyl acetate Nutrition 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 150000007513 acids Chemical class 0.000 description 7
- 125000003277 amino group Chemical group 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- 210000004623 platelet-rich plasma Anatomy 0.000 description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 6
- 238000002953 preparative HPLC Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- 101001038043 Homo sapiens Lysophosphatidic acid receptor 4 Proteins 0.000 description 5
- 102100040405 Lysophosphatidic acid receptor 4 Human genes 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 5
- 150000002430 hydrocarbons Chemical group 0.000 description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
- LYKMMUBOEFYJQG-UHFFFAOYSA-N piperoxan Chemical compound C1OC2=CC=CC=C2OC1CN1CCCCC1 LYKMMUBOEFYJQG-UHFFFAOYSA-N 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 241001529936 Murinae Species 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 229940098773 bovine serum albumin Drugs 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- 125000004185 ester group Chemical group 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 239000012160 loading buffer Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 125000003386 piperidinyl group Chemical group 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- ICDZRZKGMHSATO-UHFFFAOYSA-N 4h-1,3-benzodioxine-2-carboxylic acid Chemical class C1=CC=C2OC(C(=O)O)OCC2=C1 ICDZRZKGMHSATO-UHFFFAOYSA-N 0.000 description 3
- SWULMCRTKGDYOV-UHFFFAOYSA-N 6-chloro-4,4-dicyclohexyl-1,3-benzodioxine-2-carbonitrile Chemical compound C12=CC(Cl)=CC=C2OC(C#N)OC1(C1CCCCC1)C1CCCCC1 SWULMCRTKGDYOV-UHFFFAOYSA-N 0.000 description 3
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical class CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- 102100021977 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Human genes 0.000 description 3
- 108050004000 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Proteins 0.000 description 3
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 3
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 3
- 239000012981 Hank's balanced salt solution Substances 0.000 description 3
- 102100037611 Lysophospholipase Human genes 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 108010058864 Phospholipases A2 Proteins 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 108010022198 alkylglycerophosphoethanolamine phosphodiesterase Proteins 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 230000003915 cell function Effects 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 229940127557 pharmaceutical product Drugs 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000007790 solid phase Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 2
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- 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 description 2
- BBAUXSWABOEJLK-UHFFFAOYSA-N 4-chloro-2-[dicyclohexyl(hydroxy)methyl]phenol Chemical compound OC1=CC=C(Cl)C=C1C(O)(C1CCCCC1)C1CCCCC1 BBAUXSWABOEJLK-UHFFFAOYSA-N 0.000 description 2
- WYYPLKWWWOBYMJ-UHFFFAOYSA-N 6-chloro-4,4-dicyclohexyl-7-methoxy-1,3-benzodioxine-2-carboxylic acid Chemical compound C1=2C=C(Cl)C(OC)=CC=2OC(C(O)=O)OC1(C1CCCCC1)C1CCCCC1 WYYPLKWWWOBYMJ-UHFFFAOYSA-N 0.000 description 2
- NAPRKCTYCUXNSI-UHFFFAOYSA-N 6-chloro-4,4-dicyclohexyl-n'-hydroxy-1,3-benzodioxine-2-carboximidamide Chemical compound O1C(C(=N/O)/N)OC2=CC=C(Cl)C=C2C1(C1CCCCC1)C1CCCCC1 NAPRKCTYCUXNSI-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 2
- 101150081946 ENPP2 gene Proteins 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 108091008606 PDGF receptors Proteins 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 102000011420 Phospholipase D Human genes 0.000 description 2
- 108090000553 Phospholipase D Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- WMJMABVHDMRMJA-UHFFFAOYSA-M [Cl-].[Mg+]C1CCCCC1 Chemical compound [Cl-].[Mg+]C1CCCCC1 WMJMABVHDMRMJA-UHFFFAOYSA-M 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000008484 agonism Effects 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 230000006502 antiplatelets effects Effects 0.000 description 2
- 125000002393 azetidinyl group Chemical group 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 125000002843 carboxylic acid group Chemical group 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000001311 chemical methods and process Methods 0.000 description 2
- 210000004351 coronary vessel Anatomy 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 229960005215 dichloroacetic acid Drugs 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 125000001033 ether group Chemical group 0.000 description 2
- 150000004665 fatty acids Chemical group 0.000 description 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229960003827 isosorbide mononitrate Drugs 0.000 description 2
- YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- OFBUMTAXHZEGLX-UHFFFAOYSA-N methyl 6-chloro-4-cyclohexyl-4-phenyl-1,3-benzodioxine-2-carboxylate Chemical compound O1C(C(=O)OC)OC2=CC=C(Cl)C=C2C1(C=1C=CC=CC=1)C1CCCCC1 OFBUMTAXHZEGLX-UHFFFAOYSA-N 0.000 description 2
- 239000003094 microcapsule Substances 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 230000019499 negative regulation of cell activation Effects 0.000 description 2
- 238000006053 organic reaction Methods 0.000 description 2
- 125000000160 oxazolidinyl group Chemical group 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 230000010118 platelet activation Effects 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000000547 substituted alkyl group Chemical group 0.000 description 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 2
- 125000001984 thiazolidinyl group Chemical group 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 description 1
- 125000004529 1,2,3-triazinyl group Chemical group N1=NN=C(C=C1)* 0.000 description 1
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 description 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 description 1
- KFHQOZXAFUKFNB-UHFFFAOYSA-N 1,3-oxathiolanyl Chemical group [CH]1OCCS1 KFHQOZXAFUKFNB-UHFFFAOYSA-N 0.000 description 1
- PRIGFEJKMMRJSF-UHFFFAOYSA-M 1-fluoro-2,4,6-trimethylpyridin-1-ium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.CC1=CC(C)=[N+](F)C(C)=C1 PRIGFEJKMMRJSF-UHFFFAOYSA-M 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- NCYCYZXNIZJOKI-IOUUIBBYSA-N 11-cis-retinal Chemical compound O=C/C=C(\C)/C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-IOUUIBBYSA-N 0.000 description 1
- SYSVOKZNCITGIT-UHFFFAOYSA-N 2-[dicyclohexyl(hydroxy)methyl]-5-pyrrol-1-ylphenol Chemical compound OC1=CC(N2C=CC=C2)=CC=C1C(O)(C1CCCCC1)C1CCCCC1 SYSVOKZNCITGIT-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- NTYABNDBNKVWOO-UHFFFAOYSA-N 2h-1,3-thiazine Chemical compound C1SC=CC=N1 NTYABNDBNKVWOO-UHFFFAOYSA-N 0.000 description 1
- ZAISDHPZTZIFQF-UHFFFAOYSA-N 2h-1,4-thiazine Chemical compound C1SC=CN=C1 ZAISDHPZTZIFQF-UHFFFAOYSA-N 0.000 description 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- DYMHSSKACIQQMK-UHFFFAOYSA-N 4H-1,3-dioxine-2-carboxylic acid Chemical compound O1C(OCC=C1)C(=O)O DYMHSSKACIQQMK-UHFFFAOYSA-N 0.000 description 1
- FUGKCSRLAQKUHG-UHFFFAOYSA-N 5-chloro-2-hydroxybenzaldehyde Chemical compound OC1=CC=C(Cl)C=C1C=O FUGKCSRLAQKUHG-UHFFFAOYSA-N 0.000 description 1
- NKBASRXWGAGQDP-UHFFFAOYSA-N 5-chlorosalicylic acid Chemical compound OC(=O)C1=CC(Cl)=CC=C1O NKBASRXWGAGQDP-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- IKINCLWVNWVJIB-UHFFFAOYSA-N 6-chloro-4,4-dicyclohexyl-1,3-benzodioxine-2-carbohydrazide Chemical compound O1C(C(=O)NN)OC2=CC=C(Cl)C=C2C1(C1CCCCC1)C1CCCCC1 IKINCLWVNWVJIB-UHFFFAOYSA-N 0.000 description 1
- RVEWRHHXEILQMI-UHFFFAOYSA-N 6-chloro-4,4-dicyclohexyl-1,3-benzodioxine-2-carboxamide Chemical compound O1C(C(=O)N)OC2=CC=C(Cl)C=C2C1(C1CCCCC1)C1CCCCC1 RVEWRHHXEILQMI-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 102000000452 Acetyl-CoA carboxylase Human genes 0.000 description 1
- 108010016219 Acetyl-CoA carboxylase Proteins 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical class [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 102000001327 Chemokine CCL5 Human genes 0.000 description 1
- 108010055166 Chemokine CCL5 Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 206010011084 Coronary artery embolism Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000966782 Homo sapiens Lysophosphatidic acid receptor 1 Proteins 0.000 description 1
- 101001038001 Homo sapiens Lysophosphatidic acid receptor 2 Proteins 0.000 description 1
- 101001038006 Homo sapiens Lysophosphatidic acid receptor 3 Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 208000030514 Leukocyte adhesion deficiency type II Diseases 0.000 description 1
- 102100040607 Lysophosphatidic acid receptor 1 Human genes 0.000 description 1
- 102100040387 Lysophosphatidic acid receptor 2 Human genes 0.000 description 1
- 102100040388 Lysophosphatidic acid receptor 3 Human genes 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 101710151805 Mitochondrial intermediate peptidase 1 Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 102100040756 Rhodopsin Human genes 0.000 description 1
- 108090000820 Rhodopsin Proteins 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 238000006619 Stille reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 108700012920 TNF Proteins 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- QJRKEMJWWVXZCH-UHFFFAOYSA-M [Cl-].[Mg+]C1CCCCCC1 Chemical compound [Cl-].[Mg+]C1CCCCCC1 QJRKEMJWWVXZCH-UHFFFAOYSA-M 0.000 description 1
- QFYKHWFHKLUGAV-UHFFFAOYSA-N [Mg]C1CCCCC1 Chemical compound [Mg]C1CCCCC1 QFYKHWFHKLUGAV-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000012382 advanced drug delivery Methods 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- OSJRGDBEYARHLX-UHFFFAOYSA-N azido(trimethyl)stannane Chemical compound [N-]=[N+]=[N-].C[Sn+](C)C OSJRGDBEYARHLX-UHFFFAOYSA-N 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 125000005620 boronic acid group Chemical class 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 238000013172 carotid endarterectomy Methods 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 208000012839 conversion disease Diseases 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 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 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000004040 defense response to microbe Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 150000002013 dioxins Chemical class 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 230000002900 effect on cell Effects 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000010102 embolization Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- 230000000871 hypocholesterolemic effect Effects 0.000 description 1
- 230000000999 hypotriglyceridemic effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 125000005905 mesyloxy group Chemical group 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000006263 metalation reaction Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- FOBLNLGBEWRJLG-UHFFFAOYSA-N methyl 2-hydroxy-4-pyrrol-1-ylbenzoate Chemical compound C1=C(O)C(C(=O)OC)=CC=C1N1C=CC=C1 FOBLNLGBEWRJLG-UHFFFAOYSA-N 0.000 description 1
- KJWHRMZKJXOWFC-UHFFFAOYSA-N methyl 5-chloro-2-hydroxybenzoate Chemical compound COC(=O)C1=CC(Cl)=CC=C1O KJWHRMZKJXOWFC-UHFFFAOYSA-N 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 230000018127 platelet degranulation Effects 0.000 description 1
- 229920001992 poloxamer 407 Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920005990 polystyrene resin Polymers 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000001147 pulmonary artery Anatomy 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- CQRYARSYNCAZFO-UHFFFAOYSA-N salicyl alcohol Chemical class OCC1=CC=CC=C1O CQRYARSYNCAZFO-UHFFFAOYSA-N 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000006103 sulfonylation Effects 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000006557 surface reaction Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000004525 thiadiazinyl group Chemical group S1NN=C(C=C1)* 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- 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
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
- C07D319/08—1,3-Dioxanes; Hydrogenated 1,3-dioxanes condensed with carbocyclic rings or ring systems
-
- 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
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- 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
- A61K31/4245—Oxadiazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Cardiology (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12305553 | 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 (1)
| Publication Number | Publication Date |
|---|---|
| ES2649438T3 true ES2649438T3 (es) | 2018-01-12 |
Family
ID=48468297
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES13723767.3T Active ES2649438T3 (es) | 2012-05-18 | 2013-05-16 | Derivados de benzo[1,3]dioxina y su uso como antagonistas de LPAR5 |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US9221784B2 (enExample) |
| 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) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Family Cites Families (9)
| 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 |
| SE445553B (sv) * | 1978-05-03 | 1986-06-30 | Roussel Uclaf | /4h/-1,3-bensodioxan-2-karboxylsyraderivat |
| GB8310407D0 (en) * | 1982-05-12 | 1983-05-25 | Ici Plc | 1 3 - dioxan -5- ylalkenoic acids |
| FR2704857B1 (fr) * | 1993-05-07 | 1995-06-23 | Adir | Nouvelles benzodioxines substituées, leur procédé de préparation et les compositions pharmaceutiques les contenant. |
| EP1636585B2 (en) | 2003-05-20 | 2012-06-13 | Bayer HealthCare LLC | Diaryl ureas with kinase inhibiting activity |
| 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
-
2014
- 2014-10-20 IL IL235219A patent/IL235219A/en active IP Right Grant
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 |
| 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 |
| RU2647727C2 (ru) | 2018-03-19 |
| 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 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR102727059B1 (ko) | 설포닐우레아와 관련 화합물 및 그 용도 | |
| US6060475A (en) | Substituted pyrazin-2-yl-sulphonamide-(3-pyridyl) compounds and uses thereof | |
| BR112021011095B1 (pt) | Compostos inibidores de il-17a de imidazo[1,2-b]piridazina, composição farmacêutica que os compreende e usos dos mesmos | |
| JP2018115214A (ja) | チエノピリミジン及びチエノピリジン化合物を含有する組成物並びにそれらの使用方法 | |
| KR101780140B1 (ko) | Bace 억제제 | |
| AU2013255441B2 (en) | Substituted pyrazole compounds as CRAC modulators | |
| CA3036933A1 (en) | Trpv4 antagonists | |
| JP2016041726A (ja) | 治療特性を有する1,4−ベンゾジアゼピン−2,5−ジオンおよび関連化合物 | |
| JP5856063B2 (ja) | 治療特性を有する1,4−ベンゾジアゼピン−2,5−ジオンおよび関連化合物 | |
| WO2017060855A1 (en) | Arylcyclohexyl pyrazoles as nrf2 regulators | |
| Peng et al. | Design, synthesis, and biological evaluation of 2-(phenoxyaryl)-3-urea derivatives as novel P2Y1 receptor antagonists | |
| ES2649438T3 (es) | Derivados de benzo[1,3]dioxina y su uso como antagonistas de LPAR5 | |
| JP2020500918A (ja) | Nrf2レギュレーターとしてのn−アリールピラゾール | |
| JP2021524469A (ja) | Nrf2アクチベーターとしてのインダン | |
| RU2547465C2 (ru) | Соединение, обладающее ингибирующим действием в отношении фосфодиэстеразы 5 типа, и способ его получения | |
| ES2346081T3 (es) | Amidas de acido alcanoico sustituidas por o-heterociclos sustituidos. | |
| CA2989982C (en) | Imidazodiazepine compound | |
| ES2321299T3 (es) | Derivados de tiazol como antagonistas de npy. | |
| TW202235408A (zh) | 化合物 | |
| WO2019184744A1 (zh) | 四氢异喹啉类衍生物及其制备方法和用途 | |
| BR112017017610B1 (pt) | Composto de fórmula (ii) ou um sal ou solvato farmaceuticamente a c e i t á v e i s d o m e s m o , u s o d o c o m p o s t o o u d o s a l o u s o l v a t o farmaceuticamente aceitáveis e composição farmacêutica | |
| HK1005801B (en) | N-heteroaryl-pyridinesulfonamide derivatives and their use as endothelin antagonists |