ES2340221T3 - Compuestos y procedimientos para modular fxr. - Google Patents
Compuestos y procedimientos para modular fxr. Download PDFInfo
- Publication number
- ES2340221T3 ES2340221T3 ES07811915T ES07811915T ES2340221T3 ES 2340221 T3 ES2340221 T3 ES 2340221T3 ES 07811915 T ES07811915 T ES 07811915T ES 07811915 T ES07811915 T ES 07811915T ES 2340221 T3 ES2340221 T3 ES 2340221T3
- Authority
- ES
- Spain
- Prior art keywords
- methyl
- phenyl
- hydrogen
- alkyl
- isopropyl
- 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
- 150000001875 compounds Chemical class 0.000 title claims abstract description 190
- 238000000034 method Methods 0.000 title description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 120
- 239000001257 hydrogen Substances 0.000 claims abstract description 117
- -1 C1-C3 thiohaloalkyl Chemical group 0.000 claims abstract description 105
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 58
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 42
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 26
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 23
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims abstract description 18
- 125000001041 indolyl group Chemical group 0.000 claims abstract description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 18
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims abstract description 17
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 10
- 125000002541 furyl group Chemical group 0.000 claims abstract description 10
- 125000000168 pyrrolyl group Chemical group 0.000 claims abstract description 10
- 125000000335 thiazolyl group Chemical group 0.000 claims abstract description 10
- 125000001544 thienyl group Chemical group 0.000 claims abstract description 10
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 5
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 5
- 125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 5
- 125000005037 alkyl phenyl group Chemical group 0.000 claims abstract description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract 9
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract 2
- 239000002253 acid Substances 0.000 claims description 172
- 150000002431 hydrogen Chemical class 0.000 claims description 54
- 239000000460 chlorine Substances 0.000 claims description 52
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 47
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 46
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 41
- 229910052801 chlorine Inorganic materials 0.000 claims description 41
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 39
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 37
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 37
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 28
- 125000001153 fluoro group Chemical group F* 0.000 claims description 24
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 18
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 18
- 125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 15
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 14
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 14
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 12
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 10
- WNJCAUVBQDAAFY-UHFFFAOYSA-N 6-[4-[[3-(2,6-dichlorophenyl)-5-(trifluoromethyl)triazol-4-yl]methoxy]-2-methylphenyl]-1-propan-2-ylindazole-3-carboxylic acid Chemical compound C1=C2N(C(C)C)N=C(C(O)=O)C2=CC=C1C(C(=C1)C)=CC=C1OCC1=C(C(F)(F)F)N=NN1C1=C(Cl)C=CC=C1Cl WNJCAUVBQDAAFY-UHFFFAOYSA-N 0.000 claims description 5
- BEGCLZGRPXQHPZ-UHFFFAOYSA-N 6-[4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)triazol-4-yl]methoxy]-2-methylphenyl]-1-propan-2-ylindazole-3-carboxylic acid Chemical compound C1=C2N(C(C)C)N=C(C(O)=O)C2=CC=C1C(C(=C1)C)=CC=C1OCC1=C(C2CC2)N=NN1C1=C(Cl)C=CC=C1Cl BEGCLZGRPXQHPZ-UHFFFAOYSA-N 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 239000005711 Benzoic acid Substances 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- SQXZQHJANHWQQW-UHFFFAOYSA-N 2-methyl-4-[[methyl-[2-methyl-6-[[5-propan-2-yl-3-[2-(trifluoromethoxy)phenyl]triazol-4-yl]methoxy]pyridin-3-yl]amino]methyl]benzoic acid Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2)OC(F)(F)F)C=1COC(N=C1C)=CC=C1N(C)CC1=CC=C(C(O)=O)C(C)=C1 SQXZQHJANHWQQW-UHFFFAOYSA-N 0.000 claims 1
- ZMQNWRIWGFMCQY-UHFFFAOYSA-N 3-[[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]-n,2-dimethylanilino]methyl]benzoic acid Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC(C=C1C)=CC=C1N(C)CC1=CC=CC(C(O)=O)=C1 ZMQNWRIWGFMCQY-UHFFFAOYSA-N 0.000 claims 1
- SFYBFUNJECIUDC-UHFFFAOYSA-N 3-[[4-[[3-(2-chloro-6-fluorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]-n,2-dimethylanilino]methyl]benzoic acid Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2F)Cl)C=1COC(C=C1C)=CC=C1N(C)CC1=CC=CC(C(O)=O)=C1 SFYBFUNJECIUDC-UHFFFAOYSA-N 0.000 claims 1
- PBOQIQQEKMWEIF-UHFFFAOYSA-N 4-[[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]-n,2-dimethylanilino]methyl]benzoic acid Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC(C=C1C)=CC=C1N(C)CC1=CC=C(C(O)=O)C=C1 PBOQIQQEKMWEIF-UHFFFAOYSA-N 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 239000003981 vehicle Substances 0.000 claims 1
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 abstract description 4
- 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 abstract description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 6
- 125000001475 halogen functional group Chemical group 0.000 abstract 4
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 abstract 2
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 abstract 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 abstract 1
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 abstract 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 239
- 238000002360 preparation method Methods 0.000 description 145
- 238000006243 chemical reaction Methods 0.000 description 127
- 239000000243 solution Substances 0.000 description 107
- 150000004702 methyl esters Chemical class 0.000 description 101
- 235000019439 ethyl acetate Nutrition 0.000 description 97
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 95
- 239000000203 mixture Substances 0.000 description 94
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 75
- 230000002829 reductive effect Effects 0.000 description 73
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 72
- 229910001868 water Inorganic materials 0.000 description 70
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 61
- 239000011541 reaction mixture Substances 0.000 description 60
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
- 239000012074 organic phase Substances 0.000 description 42
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 38
- 238000005481 NMR spectroscopy Methods 0.000 description 35
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 34
- 239000012267 brine Substances 0.000 description 33
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
- 239000007787 solid Substances 0.000 description 31
- 239000007858 starting material Substances 0.000 description 29
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 26
- 238000004587 chromatography analysis Methods 0.000 description 26
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 23
- 229910052938 sodium sulfate Inorganic materials 0.000 description 23
- 235000011152 sodium sulphate Nutrition 0.000 description 23
- 238000003818 flash chromatography Methods 0.000 description 21
- 239000000377 silicon dioxide Substances 0.000 description 21
- 239000008346 aqueous phase Substances 0.000 description 19
- 239000012141 concentrate Substances 0.000 description 19
- 235000008504 concentrate Nutrition 0.000 description 19
- 239000012071 phase Substances 0.000 description 19
- 238000003756 stirring Methods 0.000 description 19
- 235000012000 cholesterol Nutrition 0.000 description 17
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 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 15
- 150000002148 esters Chemical class 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
- 239000007832 Na2SO4 Substances 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- IJVUIOCXNVEGKH-UHFFFAOYSA-N [3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methanol Chemical compound OCC1=C(C(C)C)N=NN1C1=C(Cl)C=CC=C1Cl IJVUIOCXNVEGKH-UHFFFAOYSA-N 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 10
- 229910052681 coesite Inorganic materials 0.000 description 10
- 229910052906 cristobalite Inorganic materials 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- 235000012239 silicon dioxide Nutrition 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 229910052682 stishovite Inorganic materials 0.000 description 10
- 229910052905 tridymite Inorganic materials 0.000 description 10
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
- 239000005909 Kieselgur Substances 0.000 description 9
- 239000012298 atmosphere Substances 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 125000004494 ethyl ester group Chemical group 0.000 description 8
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
- 239000006188 syrup Substances 0.000 description 8
- 235000020357 syrup Nutrition 0.000 description 8
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 8
- 238000001914 filtration Methods 0.000 description 7
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 108010010234 HDL Lipoproteins Proteins 0.000 description 6
- 102000015779 HDL Lipoproteins Human genes 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 6
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 6
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 6
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 150000003626 triacylglycerols Chemical class 0.000 description 6
- 229920002554 vinyl polymer Polymers 0.000 description 6
- HJMZTUQYJYZXAE-UHFFFAOYSA-N 1-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]-2-methylphenyl]ethanone Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC1=CC=C(C(C)=O)C(C)=C1 HJMZTUQYJYZXAE-UHFFFAOYSA-N 0.000 description 5
- NSOJWZLXHCUKPB-UHFFFAOYSA-N 2-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]-2-methylphenyl]propan-2-ol Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC1=CC=C(C(C)(C)O)C(C)=C1 NSOJWZLXHCUKPB-UHFFFAOYSA-N 0.000 description 5
- BYRWOSJFHWKXET-UHFFFAOYSA-N 2-azido-1,3-dichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1N=[N+]=[N-] BYRWOSJFHWKXET-UHFFFAOYSA-N 0.000 description 5
- CKBBSFOOIOHLPC-UHFFFAOYSA-N 6-bromo-1-benzothiophene-2-carboxylic acid Chemical compound C1=C(Br)C=C2SC(C(=O)O)=CC2=C1 CKBBSFOOIOHLPC-UHFFFAOYSA-N 0.000 description 5
- ZXMDECZLLPFSJO-UHFFFAOYSA-N 6-bromo-1-benzothiophene-3-carboxylic acid Chemical compound BrC1=CC=C2C(C(=O)O)=CSC2=C1 ZXMDECZLLPFSJO-UHFFFAOYSA-N 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 108020004999 messenger RNA Proteins 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- BWGTVPNDIBIGSB-UHFFFAOYSA-N 4-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]-2-methylphenyl]benzoic acid Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC(C=C1C)=CC=C1C1=CC=C(C(O)=O)C=C1 BWGTVPNDIBIGSB-UHFFFAOYSA-N 0.000 description 4
- GPOQODYGMUTOQL-UHFFFAOYSA-N 4-bromo-3-methylphenol Chemical compound CC1=CC(O)=CC=C1Br GPOQODYGMUTOQL-UHFFFAOYSA-N 0.000 description 4
- HYRCAPBYLWIDSN-UHFFFAOYSA-N 6-[4-[[3-(2,6-dichlorophenyl)-5-(trifluoromethyl)triazol-4-yl]methoxy]-2-methylphenyl]-1-benzothiophene-3-carboxylic acid Chemical compound C=1C=C(C=2C=C3SC=C(C3=CC=2)C(O)=O)C(C)=CC=1OCC1=C(C(F)(F)F)N=NN1C1=C(Cl)C=CC=C1Cl HYRCAPBYLWIDSN-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 4
- 108010007622 LDL Lipoproteins Proteins 0.000 description 4
- 102000007330 LDL Lipoproteins Human genes 0.000 description 4
- 102000004895 Lipoproteins Human genes 0.000 description 4
- 108090001030 Lipoproteins Proteins 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 description 4
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 4
- 229940121360 farnesoid X receptor (fxr) agonists Drugs 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- 238000005192 partition Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 235000010288 sodium nitrite Nutrition 0.000 description 4
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 4
- GRDFOBOULLNZGI-UHFFFAOYSA-N 1-(6-bromo-1-benzothiophen-3-yl)ethanone Chemical compound BrC1=CC=C2C(C(=O)C)=CSC2=C1 GRDFOBOULLNZGI-UHFFFAOYSA-N 0.000 description 3
- JRFRVSGWNMCLCN-UHFFFAOYSA-N 1-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]-2-methylphenyl]ethanol Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC1=CC=C(C(C)O)C(C)=C1 JRFRVSGWNMCLCN-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- AFKHSXFUDJNWGX-UHFFFAOYSA-N 2-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]phenyl]propan-2-ol Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC1=CC=C(C(C)(C)O)C=C1 AFKHSXFUDJNWGX-UHFFFAOYSA-N 0.000 description 3
- SNIHQVURMSAQCR-UHFFFAOYSA-N 3-(2,6-dichlorophenyl)-5-(trifluoromethyl)triazole-4-carboxylic acid Chemical compound ClC1=C(C(=CC=C1)Cl)N1N=NC(=C1C(=O)O)C(F)(F)F SNIHQVURMSAQCR-UHFFFAOYSA-N 0.000 description 3
- QMMYLIOACVLDOJ-UHFFFAOYSA-N 4-[2-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]-2-methylphenyl]propan-2-ylsulfanyl]benzoic acid Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC(C=C1C)=CC=C1C(C)(C)SC1=CC=C(C(O)=O)C=C1 QMMYLIOACVLDOJ-UHFFFAOYSA-N 0.000 description 3
- FOOWFTOIWJWIOO-UHFFFAOYSA-N 4-[2-bromo-4-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]phenyl]benzoic acid Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC(C=C1Br)=CC=C1C1=CC=C(C(O)=O)C=C1 FOOWFTOIWJWIOO-UHFFFAOYSA-N 0.000 description 3
- UIEFAJIKUVABQA-UHFFFAOYSA-N 4-[[(4-hydroxy-2-methylphenyl)methylamino]methyl]-2-methylbenzoic acid Chemical compound CC1=CC(O)=CC=C1CNCC1=CC=C(C(O)=O)C(C)=C1 UIEFAJIKUVABQA-UHFFFAOYSA-N 0.000 description 3
- WNRPYUFQIKAVOB-UHFFFAOYSA-N 4-[tert-butyl(dimethyl)silyl]oxy-n,2-dimethylaniline Chemical compound CNC1=CC=C(O[Si](C)(C)C(C)(C)C)C=C1C WNRPYUFQIKAVOB-UHFFFAOYSA-N 0.000 description 3
- BCJVBDBJSMFBRW-UHFFFAOYSA-N 4-diphenylphosphanylbutyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 BCJVBDBJSMFBRW-UHFFFAOYSA-N 0.000 description 3
- QGNGOGOOPUYKMC-UHFFFAOYSA-N 4-hydroxy-6-methylaniline Chemical compound CC1=CC(O)=CC=C1N QGNGOGOOPUYKMC-UHFFFAOYSA-N 0.000 description 3
- VZSSMDHNICMIIA-UHFFFAOYSA-N 5-[(4-bromo-3-methylphenoxy)methyl]-1-(2,6-dichlorophenyl)-4-propan-2-yltriazole Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC1=CC=C(Br)C(C)=C1 VZSSMDHNICMIIA-UHFFFAOYSA-N 0.000 description 3
- TVQGFXJSMZCLJU-UHFFFAOYSA-N 6-(4-hydroxy-2-methylphenyl)-1-propan-2-ylindazole-3-carboxylic acid Chemical compound OC1=CC(=C(C=C1)C1=CC=C2C(=NN(C2=C1)C(C)C)C(=O)O)C TVQGFXJSMZCLJU-UHFFFAOYSA-N 0.000 description 3
- QDQJIDDXPACPKY-UHFFFAOYSA-N 6-bromo-1h-indazole-3-carboxylic acid Chemical compound BrC1=CC=C2C(C(=O)O)=NNC2=C1 QDQJIDDXPACPKY-UHFFFAOYSA-N 0.000 description 3
- INNZWYJJSSRJET-UHFFFAOYSA-N 6-bromo-1h-indole-3-carboxylic acid Chemical compound BrC1=CC=C2C(C(=O)O)=CNC2=C1 INNZWYJJSSRJET-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- 101001051093 Homo sapiens Low-density lipoprotein receptor Proteins 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- WVHARBXAVPUYMQ-UHFFFAOYSA-N [3-(2,6-dichlorophenyl)-5-(trifluoromethyl)triazol-4-yl]methanol Chemical compound OCC1=C(C(F)(F)F)N=NN1C1=C(Cl)C=CC=C1Cl WVHARBXAVPUYMQ-UHFFFAOYSA-N 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- PKQUYHNHKATQGH-UHFFFAOYSA-N methyl 4-[[4-[tert-butyl(dimethyl)silyl]oxy-n,2-dimethylanilino]methyl]-2-methylbenzoate Chemical compound C1=C(C)C(C(=O)OC)=CC=C1CN(C)C1=CC=C(O[Si](C)(C)C(C)(C)C)C=C1C PKQUYHNHKATQGH-UHFFFAOYSA-N 0.000 description 3
- MOOHLFRSZUFCOU-UHFFFAOYSA-N methyl 6-(4-hydroxy-2-methylphenyl)-1-benzothiophene-2-carboxylate Chemical compound C1=C2SC(C(=O)OC)=CC2=CC=C1C1=CC=C(O)C=C1C MOOHLFRSZUFCOU-UHFFFAOYSA-N 0.000 description 3
- 108020004017 nuclear receptors Proteins 0.000 description 3
- 102000006255 nuclear receptors Human genes 0.000 description 3
- 229920000728 polyester Polymers 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000006268 reductive amination reaction Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 3
- GNLJBJNONOOOQC-UHFFFAOYSA-N $l^{3}-carbane;magnesium Chemical compound [Mg]C GNLJBJNONOOOQC-UHFFFAOYSA-N 0.000 description 2
- GKVHYRRQQVUDKB-UHFFFAOYSA-N (4-iodo-3-methylphenyl)methanol Chemical compound CC1=CC(CO)=CC=C1I GKVHYRRQQVUDKB-UHFFFAOYSA-N 0.000 description 2
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- DMLYEOVWNNHIIX-UHFFFAOYSA-N 1-(6-bromo-1-benzothiophen-2-yl)ethanone Chemical compound C1=C(Br)C=C2SC(C(=O)C)=CC2=C1 DMLYEOVWNNHIIX-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- BHXVYTQDWMQVBI-UHFFFAOYSA-N 1h-indazole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=NNC2=C1 BHXVYTQDWMQVBI-UHFFFAOYSA-N 0.000 description 2
- JDMFXJULNGEPOI-UHFFFAOYSA-N 2,6-dichloroaniline Chemical compound NC1=C(Cl)C=CC=C1Cl JDMFXJULNGEPOI-UHFFFAOYSA-N 0.000 description 2
- VLROJECCXBBKPZ-UHFFFAOYSA-N 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CC=C1O VLROJECCXBBKPZ-UHFFFAOYSA-N 0.000 description 2
- YKVWTGVTGLIRFU-UHFFFAOYSA-N 2-(4-methoxyphenyl)-1-benzothiophene-6-carboxylic acid Chemical compound COC1=CC=C(C=C1)C1=CC2=C(S1)C=C(C=C2)C(=O)O YKVWTGVTGLIRFU-UHFFFAOYSA-N 0.000 description 2
- PSTSPRRPSLWQSX-UHFFFAOYSA-N 2-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]-3-methylphenyl]propan-2-ol Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC1=CC=C(C(C)(C)O)C=C1C PSTSPRRPSLWQSX-UHFFFAOYSA-N 0.000 description 2
- WGGADQVNWRSSAA-UHFFFAOYSA-N 2-chloro-4-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]benzaldehyde Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC1=CC=C(C=O)C(Cl)=C1 WGGADQVNWRSSAA-UHFFFAOYSA-N 0.000 description 2
- AVCDACDTNHSSKU-UHFFFAOYSA-N 2-methyl-3-nitro-6-[[5-propan-2-yl-3-[2-(trifluoromethoxy)phenyl]triazol-4-yl]methoxy]pyridine Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2)OC(F)(F)F)C=1COC1=CC=C([N+]([O-])=O)C(C)=N1 AVCDACDTNHSSKU-UHFFFAOYSA-N 0.000 description 2
- JDZBJJVWKGKKNJ-UHFFFAOYSA-N 2-methyl-6-[[5-propan-2-yl-3-[2-(trifluoromethoxy)phenyl]triazol-4-yl]methoxy]pyridin-3-amine Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2)OC(F)(F)F)C=1COC1=CC=C(N)C(C)=N1 JDZBJJVWKGKKNJ-UHFFFAOYSA-N 0.000 description 2
- XXHWZPOINHDFKS-UHFFFAOYSA-N 3-[(4-hydroxy-2-methylphenyl)methylamino]benzoic acid Chemical compound OC1=CC(=C(CNC=2C=C(C(=O)O)C=CC=2)C=C1)C XXHWZPOINHDFKS-UHFFFAOYSA-N 0.000 description 2
- KQELZLCLCNPDMC-UHFFFAOYSA-N 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol Chemical compound CC1=CC(O)=CC=C1B1OC(C)(C)C(C)(C)O1 KQELZLCLCNPDMC-UHFFFAOYSA-N 0.000 description 2
- TWOIVKQTWOZVLD-UHFFFAOYSA-N 4-(4-hydroxy-2-methylphenyl)benzoic acid Chemical compound CC1=CC(O)=CC=C1C1=CC=C(C(O)=O)C=C1 TWOIVKQTWOZVLD-UHFFFAOYSA-N 0.000 description 2
- MPSRRIGZONINIX-UHFFFAOYSA-N 4-[2-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]-2-methylphenyl]ethynyl]benzoic acid Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC(C=C1C)=CC=C1C#CC1=CC=C(C(O)=O)C=C1 MPSRRIGZONINIX-UHFFFAOYSA-N 0.000 description 2
- HQBSICCBOJBSSE-UHFFFAOYSA-N 4-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]phenyl]benzonitrile Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC(C=C1)=CC=C1C1=CC=C(C#N)C=C1 HQBSICCBOJBSSE-UHFFFAOYSA-N 0.000 description 2
- MNPLTKHJEAFOCA-UHFFFAOYSA-N 4-amino-3-fluorophenol Chemical compound NC1=CC=C(O)C=C1F MNPLTKHJEAFOCA-UHFFFAOYSA-N 0.000 description 2
- GOUHYARYYWKXHS-UHFFFAOYSA-N 4-formylbenzoic acid Chemical compound OC(=O)C1=CC=C(C=O)C=C1 GOUHYARYYWKXHS-UHFFFAOYSA-N 0.000 description 2
- CLCSUIJVRRBUMI-UHFFFAOYSA-N 5-(4-hydroxy-2-methylphenyl)-4-methylthiophene-2-carboxylic acid Chemical compound OC1=CC(=C(C=C1)C1=C(C=C(S1)C(=O)O)C)C CLCSUIJVRRBUMI-UHFFFAOYSA-N 0.000 description 2
- KLWGJPJVWADJLY-UHFFFAOYSA-N 5-(bromomethyl)-1-(2,6-dichlorophenyl)-4-(trifluoromethyl)triazole Chemical compound BrCC1=C(C(F)(F)F)N=NN1C1=C(Cl)C=CC=C1Cl KLWGJPJVWADJLY-UHFFFAOYSA-N 0.000 description 2
- WURFJQTZHCBJPB-UHFFFAOYSA-N 5-(chloromethyl)-1-(2,6-dichlorophenyl)-4-propan-2-yltriazole Chemical compound ClCC1=C(C(C)C)N=NN1C1=C(Cl)C=CC=C1Cl WURFJQTZHCBJPB-UHFFFAOYSA-N 0.000 description 2
- XAZNDQISJJQOLD-UHFFFAOYSA-N 6-(4-hydroxy-2-methylphenyl)-1-methylindazole-3-carboxylic acid Chemical compound CC1=CC(O)=CC=C1C1=CC=C(C(=NN2C)C(O)=O)C2=C1 XAZNDQISJJQOLD-UHFFFAOYSA-N 0.000 description 2
- FWQJCLJQWQXNTD-UHFFFAOYSA-N 6-bromo-1,2-benzothiazole-3-carboxylic acid Chemical compound BrC1=CC=C2C(C(=O)O)=NSC2=C1 FWQJCLJQWQXNTD-UHFFFAOYSA-N 0.000 description 2
- OPJAPPYKVWTEQM-UHFFFAOYSA-N 6-bromo-1-methylindazole-3-carboxylic acid Chemical compound C1=C(Br)C=C2N(C)N=C(C(O)=O)C2=C1 OPJAPPYKVWTEQM-UHFFFAOYSA-N 0.000 description 2
- NHEDHRVSPFMKTM-UHFFFAOYSA-N 6-bromo-1-propan-2-ylindazole-3-carboxylic acid Chemical compound C1=C(Br)C=C2N(C(C)C)N=C(C(O)=O)C2=C1 NHEDHRVSPFMKTM-UHFFFAOYSA-N 0.000 description 2
- HVPQMLZLINVIHW-UHFFFAOYSA-N 6-bromo-1h-indole-2,3-dione Chemical compound BrC1=CC=C2C(=O)C(=O)NC2=C1 HVPQMLZLINVIHW-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 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
- 108010023302 HDL Cholesterol Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 238000008214 LDL Cholesterol Methods 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- VSLMMHONWGDCIE-UHFFFAOYSA-N [3-(2,6-dichlorophenyl)triazol-4-yl]methanol Chemical compound OCC1=CN=NN1C1=C(Cl)C=CC=C1Cl VSLMMHONWGDCIE-UHFFFAOYSA-N 0.000 description 2
- KZJNNOCWILZPAY-UHFFFAOYSA-N [5-cyclopropyl-3-(2,6-dichlorophenyl)triazol-4-yl]methanol Chemical compound OCC1=C(C2CC2)N=NN1C1=C(Cl)C=CC=C1Cl KZJNNOCWILZPAY-UHFFFAOYSA-N 0.000 description 2
- DGIDOZFYSGWFLD-UHFFFAOYSA-N [5-propan-2-yl-3-[2-(trifluoromethoxy)phenyl]triazol-4-yl]methanol Chemical compound OCC1=C(C(C)C)N=NN1C1=CC=CC=C1OC(F)(F)F DGIDOZFYSGWFLD-UHFFFAOYSA-N 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- WDJHALXBUFZDSR-UHFFFAOYSA-M acetoacetate Chemical compound CC(=O)CC([O-])=O WDJHALXBUFZDSR-UHFFFAOYSA-M 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- NYZUSXJYUGDVCE-UHFFFAOYSA-N benzyl n-[4-[tert-butyl(dimethyl)silyl]oxy-2-methylphenyl]carbamate Chemical compound CC1=CC(O[Si](C)(C)C(C)(C)C)=CC=C1NC(=O)OCC1=CC=CC=C1 NYZUSXJYUGDVCE-UHFFFAOYSA-N 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 239000013058 crude material Substances 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 2
- 125000003963 dichloro group Chemical group Cl* 0.000 description 2
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 230000009931 harmful effect Effects 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- UYFFMVDJHCONSM-UHFFFAOYSA-N methyl 5-cyclopropyl-3-(2,6-dichlorophenyl)triazole-4-carboxylate Chemical compound COC(=O)C1=C(C2CC2)N=NN1C1=C(Cl)C=CC=C1Cl UYFFMVDJHCONSM-UHFFFAOYSA-N 0.000 description 2
- SFDVDNLBYGHFNF-UHFFFAOYSA-N methyl 6-bromo-1-benzothiophene-2-carboxylate Chemical compound C1=C(Br)C=C2SC(C(=O)OC)=CC2=C1 SFDVDNLBYGHFNF-UHFFFAOYSA-N 0.000 description 2
- SKZJYJMYLUQJPG-UHFFFAOYSA-N methyl 6-bromo-1h-indole-3-carboxylate Chemical compound BrC1=CC=C2C(C(=O)OC)=CNC2=C1 SKZJYJMYLUQJPG-UHFFFAOYSA-N 0.000 description 2
- 125000006431 methyl cyclopropyl group Chemical group 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 2
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 101150096065 shp gene Proteins 0.000 description 2
- VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical group COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 2
- AMSQNQJCBXQYEX-UHFFFAOYSA-N (4-methoxy-2-methylphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C(C)=C1 AMSQNQJCBXQYEX-UHFFFAOYSA-N 0.000 description 1
- OQJBFFCUFALWQL-BUHFOSPRSA-N (ne)-n-(piperidine-1-carbonylimino)piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)\N=N\C(=O)N1CCCCC1 OQJBFFCUFALWQL-BUHFOSPRSA-N 0.000 description 1
- KPZGRMZPZLOPBS-UHFFFAOYSA-N 1,3-dichloro-2,2-bis(chloromethyl)propane Chemical compound ClCC(CCl)(CCl)CCl KPZGRMZPZLOPBS-UHFFFAOYSA-N 0.000 description 1
- QWJXSJYZEGFYMN-UHFFFAOYSA-N 1-(2,6-dichlorophenyl)-5-[(4-iodophenoxy)methyl]-4-propan-2-yltriazole Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC1=CC=C(I)C=C1 QWJXSJYZEGFYMN-UHFFFAOYSA-N 0.000 description 1
- RSIBPQAQMPALQP-UHFFFAOYSA-N 1-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]-3-methylphenyl]ethanone Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC1=CC=C(C(C)=O)C=C1C RSIBPQAQMPALQP-UHFFFAOYSA-N 0.000 description 1
- VOTDEEOHADERAE-UHFFFAOYSA-N 1-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]phenyl]ethanone Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC1=CC=C(C(C)=O)C=C1 VOTDEEOHADERAE-UHFFFAOYSA-N 0.000 description 1
- CWJRXPQCOQFJKZ-UHFFFAOYSA-N 1-[4-[[3-(2-chloro-6-fluorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]-2-methylphenyl]ethanol Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2F)Cl)C=1COC1=CC=C(C(C)O)C(C)=C1 CWJRXPQCOQFJKZ-UHFFFAOYSA-N 0.000 description 1
- WXVYVHTYSXWCOD-UHFFFAOYSA-N 1-[4-[[3-(2-chloro-6-fluorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]-2-methylphenyl]ethanone Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2F)Cl)C=1COC1=CC=C(C(C)=O)C(C)=C1 WXVYVHTYSXWCOD-UHFFFAOYSA-N 0.000 description 1
- KNPDKRVXJOVOQP-UHFFFAOYSA-N 1-azido-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1N=[N+]=[N-] KNPDKRVXJOVOQP-UHFFFAOYSA-N 0.000 description 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
- SBFBCWSHVLCQPK-UHFFFAOYSA-N 2-(4-hydroxyphenyl)-1-benzothiophene-6-carboxylic acid Chemical compound OC1=CC=C(C=C1)C1=CC2=C(S1)C=C(C=C2)C(=O)O SBFBCWSHVLCQPK-UHFFFAOYSA-N 0.000 description 1
- VZUFJMKTXKURRI-UHFFFAOYSA-N 2-(4-methoxyphenyl)-1-benzothiophen-6-ol Chemical compound C1=CC(OC)=CC=C1C1=CC2=CC=C(O)C=C2S1 VZUFJMKTXKURRI-UHFFFAOYSA-N 0.000 description 1
- ORXSLDYRYTVAPC-UHFFFAOYSA-N 2-(4-sulfanylphenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(S)C=C1 ORXSLDYRYTVAPC-UHFFFAOYSA-N 0.000 description 1
- BSYVHEMZTXJMFN-UHFFFAOYSA-N 2-(6-bromo-1h-indol-3-yl)acetic acid Chemical compound BrC1=CC=C2C(CC(=O)O)=CNC2=C1 BSYVHEMZTXJMFN-UHFFFAOYSA-N 0.000 description 1
- ORIMWFSTFMIQOL-UHFFFAOYSA-N 2-(azidomethyl)-1,3-dichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1CN=[N+]=[N-] ORIMWFSTFMIQOL-UHFFFAOYSA-N 0.000 description 1
- KRQUFUKTQHISJB-YYADALCUSA-N 2-[(E)-N-[2-(4-chlorophenoxy)propoxy]-C-propylcarbonimidoyl]-3-hydroxy-5-(thian-3-yl)cyclohex-2-en-1-one Chemical compound CCC\C(=N/OCC(C)OC1=CC=C(Cl)C=C1)C1=C(O)CC(CC1=O)C1CCCSC1 KRQUFUKTQHISJB-YYADALCUSA-N 0.000 description 1
- BCQGNLYGARVVBO-UHFFFAOYSA-N 2-azido-1-chloro-3-fluorobenzene Chemical compound FC1=CC=CC(Cl)=C1N=[N+]=[N-] BCQGNLYGARVVBO-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- KMQWNQKESAHDKD-UHFFFAOYSA-N 2-chloro-4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C(Cl)=C1 KMQWNQKESAHDKD-UHFFFAOYSA-N 0.000 description 1
- KKZUMAMOMRDVKA-UHFFFAOYSA-N 2-chloropropane Chemical group [CH2]C(C)Cl KKZUMAMOMRDVKA-UHFFFAOYSA-N 0.000 description 1
- OGVPJBJWJCZBTH-UHFFFAOYSA-N 2-methyl-4-phenylmethoxybenzaldehyde Chemical compound C1=C(C=O)C(C)=CC(OCC=2C=CC=CC=2)=C1 OGVPJBJWJCZBTH-UHFFFAOYSA-N 0.000 description 1
- XRBHBMGGZBBEPS-UHFFFAOYSA-N 3-(2,6-dichlorophenyl)triazole-4-carbaldehyde Chemical compound ClC1=CC=CC(Cl)=C1N1C(C=O)=CN=N1 XRBHBMGGZBBEPS-UHFFFAOYSA-N 0.000 description 1
- FZKURNSIBVVIEU-UHFFFAOYSA-N 3-(diethoxyphosphorylmethyl)benzoic acid Chemical compound CCOP(=O)(OCC)CC1=CC=CC(C(O)=O)=C1 FZKURNSIBVVIEU-UHFFFAOYSA-N 0.000 description 1
- FFFUYAAIQHIBGO-UHFFFAOYSA-N 3-[2-(2-chloro-4-hydroxyphenyl)ethenyl]benzoic acid Chemical compound ClC1=C(C=CC(=C1)O)C=CC=1C=C(C(=O)O)C=CC=1 FFFUYAAIQHIBGO-UHFFFAOYSA-N 0.000 description 1
- PZRKGYTTXMQINL-UHFFFAOYSA-N 3-[2-(4-hydroxy-2-methylphenyl)ethenyl]benzoic acid Chemical compound OC1=CC(=C(C=C1)C=CC=1C=C(C(=O)O)C=CC=1)C PZRKGYTTXMQINL-UHFFFAOYSA-N 0.000 description 1
- SRGOULZPFPICCH-UHFFFAOYSA-N 3-[[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]-2-methylphenyl]methylamino]benzoic acid Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC(C=C1C)=CC=C1CNC1=CC=CC(C(O)=O)=C1 SRGOULZPFPICCH-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
- VWXZFDWVWMQRQR-UHFFFAOYSA-N 3-ethenylbenzoic acid Chemical compound OC(=O)C1=CC=CC(C=C)=C1 VWXZFDWVWMQRQR-UHFFFAOYSA-N 0.000 description 1
- CSSGKHVRDGATJL-UHFFFAOYSA-N 3-fluoro-4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C(F)=C1 CSSGKHVRDGATJL-UHFFFAOYSA-N 0.000 description 1
- IFLKEBSJTZGCJG-UHFFFAOYSA-N 3-methylthiophene-2-carboxylic acid Chemical compound CC=1C=CSC=1C(O)=O IFLKEBSJTZGCJG-UHFFFAOYSA-N 0.000 description 1
- RSFDFESMVAIVKO-UHFFFAOYSA-N 3-sulfanylbenzoic acid Chemical compound OC(=O)C1=CC=CC(S)=C1 RSFDFESMVAIVKO-UHFFFAOYSA-N 0.000 description 1
- LZPWAYBEOJRFAX-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2$l^{2}-dioxaborolane Chemical compound CC1(C)O[B]OC1(C)C LZPWAYBEOJRFAX-UHFFFAOYSA-N 0.000 description 1
- WJTGJOMNVLBCHY-UHFFFAOYSA-N 4-(2-amino-4-methoxyphenyl)-3-methylbenzoic acid Chemical compound CC1=C(C=CC(=C1)C(=O)O)C1=C(C=C(C=C1)OC)N WJTGJOMNVLBCHY-UHFFFAOYSA-N 0.000 description 1
- CJOMQWCFIJYADH-UHFFFAOYSA-N 4-(2-amino-4-methoxyphenyl)benzoic acid Chemical compound NC1=CC(OC)=CC=C1C1=CC=C(C(O)=O)C=C1 CJOMQWCFIJYADH-UHFFFAOYSA-N 0.000 description 1
- AWFRVNVVKAVFGF-UHFFFAOYSA-N 4-(2-bromo-4-hydroxyphenyl)benzoic acid Chemical compound BrC1=C(C=CC(=C1)O)C1=CC=C(C=C1)C(=O)O AWFRVNVVKAVFGF-UHFFFAOYSA-N 0.000 description 1
- GJZNWKYDSWFGBE-UHFFFAOYSA-N 4-(2-bromo-4-methoxyphenyl)benzoic acid Chemical compound BrC1=C(C=CC(=C1)OC)C1=CC=C(C=C1)C(=O)O GJZNWKYDSWFGBE-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
- ZEAMNAZHLUADKR-UHFFFAOYSA-N 4-(4-hydroxy-2-methylphenyl)-3-methylbenzoic acid Chemical compound OC1=CC(=C(C=C1)C1=C(C=C(C=C1)C(=O)O)C)C ZEAMNAZHLUADKR-UHFFFAOYSA-N 0.000 description 1
- LSXDVQPWVWTBHJ-UHFFFAOYSA-N 4-(4-methoxy-2-nitrophenyl)benzoic acid Chemical compound [O-][N+](=O)C1=CC(OC)=CC=C1C1=CC=C(C(O)=O)C=C1 LSXDVQPWVWTBHJ-UHFFFAOYSA-N 0.000 description 1
- JZOMEDWODRISKH-UHFFFAOYSA-N 4-[(4-hydroxy-2-methylphenyl)methylamino]benzoic acid Chemical compound OC1=CC(=C(CNC2=CC=C(C(=O)O)C=C2)C=C1)C JZOMEDWODRISKH-UHFFFAOYSA-N 0.000 description 1
- QNOAFTXJCHMKGF-UHFFFAOYSA-N 4-[(4-hydroxy-N,2-dimethylanilino)methyl]benzoic acid Chemical compound OC1=CC(=C(C=C1)N(C)CC1=CC=C(C(=O)O)C=C1)C QNOAFTXJCHMKGF-UHFFFAOYSA-N 0.000 description 1
- ZNLNZGXCIQVWAE-UHFFFAOYSA-N 4-[2-bromo-4-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]phenyl]benzoyl chloride Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC(C=C1Br)=CC=C1C1=CC=C(C(Cl)=O)C=C1 ZNLNZGXCIQVWAE-UHFFFAOYSA-N 0.000 description 1
- NPPPORJZPNJXNQ-UHFFFAOYSA-N 4-amino-3-(trifluoromethyl)benzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1C(F)(F)F NPPPORJZPNJXNQ-UHFFFAOYSA-N 0.000 description 1
- SJXHLZCPDZPBPW-UHFFFAOYSA-N 4-ethynylbenzoic acid Chemical compound OC(=O)C1=CC=C(C#C)C=C1 SJXHLZCPDZPBPW-UHFFFAOYSA-N 0.000 description 1
- OIWOOOJFKXTXKV-UHFFFAOYSA-N 4-formyl-2-methylbenzoic acid Chemical compound CC1=CC(C=O)=CC=C1C(O)=O OIWOOOJFKXTXKV-UHFFFAOYSA-N 0.000 description 1
- IAMNVCJECQWBLZ-UHFFFAOYSA-N 4-hydroxy-2-methylacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1C IAMNVCJECQWBLZ-UHFFFAOYSA-N 0.000 description 1
- CBSHYVOSDAFWEQ-UHFFFAOYSA-N 5-(4-methoxy-2-methylphenyl)-4-methylthiophene-2-carboxylic acid Chemical compound CC1=CC(OC)=CC=C1C1=C(C)C=C(C(O)=O)S1 CBSHYVOSDAFWEQ-UHFFFAOYSA-N 0.000 description 1
- JVZMBSGNSAHFCY-UHFFFAOYSA-N 5-bromo-1h-indole-3-carboxylic acid Chemical compound C1=C(Br)C=C2C(C(=O)O)=CNC2=C1 JVZMBSGNSAHFCY-UHFFFAOYSA-N 0.000 description 1
- ZFCKHGGZIIUHSX-UHFFFAOYSA-N 6-(4-hydroxy-2-methylphenyl)-1,2-benzothiazole-3-carboxylic acid Chemical compound CC1=CC(O)=CC=C1C1=CC=C(C(=NS2)C(O)=O)C2=C1 ZFCKHGGZIIUHSX-UHFFFAOYSA-N 0.000 description 1
- YKDZFPHOWKBVFD-UHFFFAOYSA-N 6-(4-hydroxy-2-methylphenyl)-1-benzothiophene-3-carboxylic acid Chemical compound OC1=CC(=C(C=C1)C=1C=CC2=C(SC=C2C(=O)O)C=1)C YKDZFPHOWKBVFD-UHFFFAOYSA-N 0.000 description 1
- OQIMJOXSDVGEBU-UHFFFAOYSA-N 6-bromo-1-benzothiophene Chemical compound BrC1=CC=C2C=CSC2=C1 OQIMJOXSDVGEBU-UHFFFAOYSA-N 0.000 description 1
- KYUKAQJZFKJZBZ-UHFFFAOYSA-N 6-bromo-1-methylindole-3-carboxylic acid Chemical compound C1=C(Br)C=C2N(C)C=C(C(O)=O)C2=C1 KYUKAQJZFKJZBZ-UHFFFAOYSA-N 0.000 description 1
- GHSRMSJVYMITDX-UHFFFAOYSA-N 6-chloro-2-methyl-3-nitropyridine Chemical compound CC1=NC(Cl)=CC=C1[N+]([O-])=O GHSRMSJVYMITDX-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 200000000007 Arterial disease Diseases 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- 241000206761 Bacillariophyta Species 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- BTSVZJOJHBKKPM-UHFFFAOYSA-N Cc1cc(O)ccc1-c1ccc2c(cn(C)c2c1)C(O)=O Chemical compound Cc1cc(O)ccc1-c1ccc2c(cn(C)c2c1)C(O)=O BTSVZJOJHBKKPM-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010008635 Cholestasis Diseases 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000600434 Homo sapiens Putative uncharacterized protein encoded by MIR7-3HG Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 108010061306 Lipoprotein Receptors Proteins 0.000 description 1
- 102000011965 Lipoprotein Receptors Human genes 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102100037401 Putative uncharacterized protein encoded by MIR7-3HG Human genes 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 235000021068 Western diet Nutrition 0.000 description 1
- DMKWUTRWUQHDNU-UHFFFAOYSA-N [3-(2,6-dichlorophenyl)-5-methyltriazol-4-yl]methanol Chemical compound OCC1=C(C)N=NN1C1=C(Cl)C=CC=C1Cl DMKWUTRWUQHDNU-UHFFFAOYSA-N 0.000 description 1
- SVAOLOVRQXHLNP-UHFFFAOYSA-N [3-[2-(trifluoromethoxy)phenyl]-5-(trifluoromethyl)triazol-4-yl]methanol Chemical compound OCC1=C(C(F)(F)F)N=NN1C1=CC=CC=C1OC(F)(F)F SVAOLOVRQXHLNP-UHFFFAOYSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- RFFNMBRSBYMCJM-UHFFFAOYSA-N [4-[tert-butyl(dimethyl)silyl]oxy-2-methylphenyl]-methylcarbamic acid Chemical compound C(C)(C)(C)[Si](OC1=CC(=C(C=C1)N(C(O)=O)C)C)(C)C RFFNMBRSBYMCJM-UHFFFAOYSA-N 0.000 description 1
- RBZZODHMVOFEBW-UHFFFAOYSA-N [5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]triazol-4-yl]methanol Chemical compound OCC1=C(C2CC2)N=NN1C1=CC=CC=C1OC(F)(F)F RBZZODHMVOFEBW-UHFFFAOYSA-N 0.000 description 1
- CWXIBGNCALIFNG-UHFFFAOYSA-N [5-propan-2-yl-3-[2-(trifluoromethyl)phenyl]triazol-4-yl]methanol Chemical compound OCC1=C(C(C)C)N=NN1C1=CC=CC=C1C(F)(F)F CWXIBGNCALIFNG-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- SVOKLYOZVAMYNV-UHFFFAOYSA-N benzyl n-[4-[tert-butyl(dimethyl)silyl]oxy-2-methylphenyl]-n-methylcarbamate Chemical compound C=1C=C(O[Si](C)(C)C(C)(C)C)C=C(C)C=1N(C)C(=O)OCC1=CC=CC=C1 SVOKLYOZVAMYNV-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 125000003865 brosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)S(*)(=O)=O 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 230000036996 cardiovascular health Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 1
- 230000007870 cholestasis Effects 0.000 description 1
- 231100000359 cholestasis Toxicity 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- KFGVRWGDTLZAAO-UHFFFAOYSA-N cyclopenta-1,3-diene dicyclohexyl(cyclopenta-1,3-dien-1-yl)phosphane iron(2+) Chemical compound [Fe++].c1cc[cH-]c1.C1CCC(CC1)P(C1CCCCC1)c1ccc[cH-]1 KFGVRWGDTLZAAO-UHFFFAOYSA-N 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- MDHVAGISVVVEJD-UHFFFAOYSA-N diazonio-[2-(trifluoromethoxy)phenyl]azanide Chemical compound FC(F)(F)OC1=CC=CC=C1N=[N+]=[N-] MDHVAGISVVVEJD-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
- GMLFPSKPTROTFV-UHFFFAOYSA-N dimethylborane Chemical compound CBC GMLFPSKPTROTFV-UHFFFAOYSA-N 0.000 description 1
- UZUODNWWWUQRIR-UHFFFAOYSA-L disodium;3-aminonaphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].C1=CC=C(S([O-])(=O)=O)C2=CC(N)=CC(S([O-])(=O)=O)=C21 UZUODNWWWUQRIR-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- QGBQGMHXBSLYLZ-UHFFFAOYSA-N ditert-butyl-(1-naphthalen-1-ylnaphthalen-2-yl)phosphane Chemical group C1=CC=C2C(C3=C4C=CC=CC4=CC=C3P(C(C)(C)C)C(C)(C)C)=CC=CC2=C1 QGBQGMHXBSLYLZ-UHFFFAOYSA-N 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- DQDPZIRMUJBHTI-UHFFFAOYSA-N ethyl 3-(2,6-dichlorophenyl)-5-propan-2-yltriazole-4-carboxylate Chemical compound CCOC(=O)C1=C(C(C)C)N=NN1C1=C(Cl)C=CC=C1Cl DQDPZIRMUJBHTI-UHFFFAOYSA-N 0.000 description 1
- AZDNWEDRRSBDTN-UHFFFAOYSA-N ethyl 3-[2-(trifluoromethoxy)phenyl]-5-(trifluoromethyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=C(C(F)(F)F)N=NN1C1=CC=CC=C1OC(F)(F)F AZDNWEDRRSBDTN-UHFFFAOYSA-N 0.000 description 1
- OLLQMJGUPHIYRE-UHFFFAOYSA-N ethyl 5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]triazole-4-carboxylate Chemical compound CCOC(=O)C1=C(C2CC2)N=NN1C1=CC=CC=C1OC(F)(F)F OLLQMJGUPHIYRE-UHFFFAOYSA-N 0.000 description 1
- VXTYEVFIIYBRAN-UHFFFAOYSA-N ethyl 5-propan-2-yl-3-[2-(trifluoromethoxy)phenyl]triazole-4-carboxylate Chemical compound CCOC(=O)C1=C(C(C)C)N=NN1C1=CC=CC=C1OC(F)(F)F VXTYEVFIIYBRAN-UHFFFAOYSA-N 0.000 description 1
- ANRHEXOCPIXZLT-UHFFFAOYSA-N ethyl 5-propan-2-yl-3-[2-(trifluoromethyl)phenyl]triazole-4-carboxylate Chemical compound CCOC(=O)C1=C(C(C)C)N=NN1C1=CC=CC=C1C(F)(F)F ANRHEXOCPIXZLT-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910000856 hastalloy Inorganic materials 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration 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
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 108010003814 member 2 group B nuclear receptor subfamily 0 Proteins 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- KJKMOADDOGZYQC-UHFFFAOYSA-N methyl 2-(2-trimethylsilylethynyl)benzoate Chemical compound COC(=O)C1=CC=CC=C1C#C[Si](C)(C)C KJKMOADDOGZYQC-UHFFFAOYSA-N 0.000 description 1
- VXQZIUJCGSIQEL-UHFFFAOYSA-N methyl 2-butoxy-4-[[4-[tert-butyl(dimethyl)silyl]oxy-n,2-dimethylanilino]methyl]benzoate Chemical compound C1=C(C(=O)OC)C(OCCCC)=CC(CN(C)C=2C(=CC(O[Si](C)(C)C(C)(C)C)=CC=2)C)=C1 VXQZIUJCGSIQEL-UHFFFAOYSA-N 0.000 description 1
- FIKBYSIYPIRVFD-UHFFFAOYSA-N methyl 2-butoxy-4-formylbenzoate Chemical compound CCCCOC1=CC(C=O)=CC=C1C(=O)OC FIKBYSIYPIRVFD-UHFFFAOYSA-N 0.000 description 1
- PVIUEUMDWMVZLZ-UHFFFAOYSA-N methyl 3-(2,6-dichlorophenyl)-5-methyltriazole-4-carboxylate Chemical compound COC(=O)C1=C(C)N=NN1C1=C(Cl)C=CC=C1Cl PVIUEUMDWMVZLZ-UHFFFAOYSA-N 0.000 description 1
- NSXWMGYQHNWJQL-UHFFFAOYSA-N methyl 3-(2-trimethylsilylethynyl)benzoate Chemical compound COC(=O)C1=CC=CC(C#C[Si](C)(C)C)=C1 NSXWMGYQHNWJQL-UHFFFAOYSA-N 0.000 description 1
- OZYAYUCDARXTOH-UHFFFAOYSA-N methyl 3-[(4-hydroxy-n,2-dimethylanilino)methyl]benzoate Chemical compound COC(=O)C1=CC=CC(CN(C)C=2C(=CC(O)=CC=2)C)=C1 OZYAYUCDARXTOH-UHFFFAOYSA-N 0.000 description 1
- DDXZMLZQQWVSRX-UHFFFAOYSA-N methyl 3-ethynylbenzoate Chemical compound COC(=O)C1=CC=CC(C#C)=C1 DDXZMLZQQWVSRX-UHFFFAOYSA-N 0.000 description 1
- CSALCOFYVWMQBG-UHFFFAOYSA-N methyl 4-(2-chloro-4-hydroxyphenyl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=C(O)C=C1Cl CSALCOFYVWMQBG-UHFFFAOYSA-N 0.000 description 1
- RAEVMJRGBGCZIM-UHFFFAOYSA-N methyl 4-(2-fluoro-4-hydroxyphenyl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=C(O)C=C1F RAEVMJRGBGCZIM-UHFFFAOYSA-N 0.000 description 1
- FWGOAHUFSIVCPG-UHFFFAOYSA-N methyl 4-(4-hydroxy-2-nitrophenyl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=C(O)C=C1[N+]([O-])=O FWGOAHUFSIVCPG-UHFFFAOYSA-N 0.000 description 1
- JGNBKQHCVAPTTM-UHFFFAOYSA-N methyl 4-(4-hydroxy-3-methylphenyl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=C(O)C(C)=C1 JGNBKQHCVAPTTM-UHFFFAOYSA-N 0.000 description 1
- YRTRIWWUUJJESV-UHFFFAOYSA-N methyl 4-[(4-hydroxy-2-methylanilino)methyl]-2-methylbenzoate Chemical compound C1=C(C)C(C(=O)OC)=CC=C1CNC1=CC=C(O)C=C1C YRTRIWWUUJJESV-UHFFFAOYSA-N 0.000 description 1
- WEKDWRRJMSBWOK-UHFFFAOYSA-N methyl 4-[(4-hydroxy-2-methylphenyl)methylamino]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1NCC1=CC=C(O)C=C1C WEKDWRRJMSBWOK-UHFFFAOYSA-N 0.000 description 1
- UUDJXADZYZXWPC-UHFFFAOYSA-N methyl 4-[(4-hydroxy-n,2-dimethylanilino)methyl]-2-(trifluoromethyl)benzoate Chemical compound C1=C(C(F)(F)F)C(C(=O)OC)=CC=C1CN(C)C1=CC=C(O)C=C1C UUDJXADZYZXWPC-UHFFFAOYSA-N 0.000 description 1
- WQIOUBBFTOIXBD-UHFFFAOYSA-N methyl 4-[4-hydroxy-2-(trifluoromethyl)phenyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=C(O)C=C1C(F)(F)F WQIOUBBFTOIXBD-UHFFFAOYSA-N 0.000 description 1
- JPGRSTBIEYGVNO-UHFFFAOYSA-N methyl 4-ethynylbenzoate Chemical compound COC(=O)C1=CC=C(C#C)C=C1 JPGRSTBIEYGVNO-UHFFFAOYSA-N 0.000 description 1
- CGGGWRDRBMSXOL-UHFFFAOYSA-N methyl 4-formyl-2-(trifluoromethyl)benzoate Chemical compound COC(=O)C1=CC=C(C=O)C=C1C(F)(F)F CGGGWRDRBMSXOL-UHFFFAOYSA-N 0.000 description 1
- LHJKZERUIPGPCK-UHFFFAOYSA-N methyl 4-formyl-2-methylbenzoate Chemical compound COC(=O)C1=CC=C(C=O)C=C1C LHJKZERUIPGPCK-UHFFFAOYSA-N 0.000 description 1
- BTZOMWXSWVOOHG-UHFFFAOYSA-N methyl 4-sulfanylbenzoate Chemical compound COC(=O)C1=CC=C(S)C=C1 BTZOMWXSWVOOHG-UHFFFAOYSA-N 0.000 description 1
- LIQIPOFQWQLBCQ-UHFFFAOYSA-N methyl 5-(4-hydroxy-2-methylphenyl)thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1C1=CC=C(O)C=C1C LIQIPOFQWQLBCQ-UHFFFAOYSA-N 0.000 description 1
- MSCOMZNDKVOGGI-UHFFFAOYSA-N methyl 5-(4-hydroxyphenyl)thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1C1=CC=C(O)C=C1 MSCOMZNDKVOGGI-UHFFFAOYSA-N 0.000 description 1
- RJWZFHRMQRWEIH-UHFFFAOYSA-N methyl 5-bromo-4-methylthiophene-2-carboxylate Chemical compound COC(=O)C1=CC(C)=C(Br)S1 RJWZFHRMQRWEIH-UHFFFAOYSA-N 0.000 description 1
- INSNZBHWOMPOKH-UHFFFAOYSA-N methyl 6-(4-hydroxy-2-methylphenyl)-1-benzothiophene-3-carboxylate Chemical compound C=1C=C2C(C(=O)OC)=CSC2=CC=1C1=CC=C(O)C=C1C INSNZBHWOMPOKH-UHFFFAOYSA-N 0.000 description 1
- NRTWWGSSWOLVHM-UHFFFAOYSA-N methyl 6-(4-hydroxy-2-methylphenyl)-1-methylindole-3-carboxylate Chemical compound C=1C=C2C(C(=O)OC)=CN(C)C2=CC=1C1=CC=C(O)C=C1C NRTWWGSSWOLVHM-UHFFFAOYSA-N 0.000 description 1
- XXEWKZYLPOJIIL-UHFFFAOYSA-N methyl 6-(4-hydroxy-2-methylphenyl)-1-propan-2-ylindole-3-carboxylate Chemical compound C=1C=C2C(C(=O)OC)=CN(C(C)C)C2=CC=1C1=CC=C(O)C=C1C XXEWKZYLPOJIIL-UHFFFAOYSA-N 0.000 description 1
- RLMWPNDSVWJWHA-UHFFFAOYSA-N methyl 6-bromo-1-methylindole-3-carboxylate Chemical compound BrC1=CC=C2C(C(=O)OC)=CN(C)C2=C1 RLMWPNDSVWJWHA-UHFFFAOYSA-N 0.000 description 1
- HVSAEJIBGMVUJK-UHFFFAOYSA-N methyl 6-bromo-1-propan-2-ylindole-3-carboxylate Chemical compound BrC1=CC=C2C(C(=O)OC)=CN(C(C)C)C2=C1 HVSAEJIBGMVUJK-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- OQJBFFCUFALWQL-UHFFFAOYSA-N n-(piperidine-1-carbonylimino)piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)N=NC(=O)N1CCCCC1 OQJBFFCUFALWQL-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- CTRLRINCMYICJO-UHFFFAOYSA-N phenyl azide Chemical class [N-]=[N+]=NC1=CC=CC=C1 CTRLRINCMYICJO-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- BHRZNVHARXXAHW-UHFFFAOYSA-N sec-butylamine Chemical compound CCC(C)N BHRZNVHARXXAHW-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- YNVOMSDITJMNET-UHFFFAOYSA-N thiophene-3-carboxylic acid Chemical compound OC(=O)C=1C=CSC=1 YNVOMSDITJMNET-UHFFFAOYSA-N 0.000 description 1
- 108090000721 thyroid hormone receptors Proteins 0.000 description 1
- 102000004217 thyroid hormone receptors Human genes 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- ZMCBYSBVJIMENC-UHFFFAOYSA-N tricaine Chemical compound CCOC(=O)C1=CC=CC(N)=C1 ZMCBYSBVJIMENC-UHFFFAOYSA-N 0.000 description 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
- DQWPFSLDHJDLRL-UHFFFAOYSA-N triethyl phosphate Chemical compound CCOP(=O)(OCC)OCC DQWPFSLDHJDLRL-UHFFFAOYSA-N 0.000 description 1
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-O triphenylphosphanium Chemical compound C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-O 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- CITILBVTAYEWKR-UHFFFAOYSA-L zinc trifluoromethanesulfonate Chemical compound [Zn+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F CITILBVTAYEWKR-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- 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
- C07D403/12—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
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US80810406P | 2006-05-24 | 2006-05-24 | |
| US808104P | 2006-05-24 | ||
| US87000106P | 2006-12-14 | 2006-12-14 | |
| US870001P | 2006-12-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2340221T3 true ES2340221T3 (es) | 2010-05-31 |
Family
ID=38626336
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES07811915T Active ES2340221T3 (es) | 2006-05-24 | 2007-05-22 | Compuestos y procedimientos para modular fxr. |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US8106077B2 (enExample) |
| EP (1) | EP2029558B1 (enExample) |
| JP (1) | JP5225984B2 (enExample) |
| AR (1) | AR061101A1 (enExample) |
| AT (1) | ATE460403T1 (enExample) |
| AU (1) | AU2007267692B2 (enExample) |
| BR (1) | BRPI0711875A2 (enExample) |
| CA (1) | CA2651373A1 (enExample) |
| CL (1) | CL2007001451A1 (enExample) |
| DE (1) | DE602007005256D1 (enExample) |
| EA (1) | EA014720B1 (enExample) |
| ES (1) | ES2340221T3 (enExample) |
| MX (1) | MX2008014959A (enExample) |
| PE (1) | PE20080259A1 (enExample) |
| TW (1) | TW200812982A (enExample) |
| WO (1) | WO2007140174A2 (enExample) |
Families Citing this family (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1894928A1 (en) * | 2006-08-29 | 2008-03-05 | PheneX Pharmaceuticals AG | Heterocyclic fxr binding compounds |
| EP1894924A1 (en) * | 2006-08-29 | 2008-03-05 | Phenex Pharmaceuticals AG | Heterocyclic FXR binding compounds |
| TW200906823A (en) * | 2007-07-16 | 2009-02-16 | Lilly Co Eli | Compounds and methods for modulating FXR |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| JP2011507909A (ja) | 2007-12-20 | 2011-03-10 | エンビボ ファーマシューティカルズ インコーポレイテッド | 四置換ベンゼン |
| US8263630B2 (en) | 2008-02-12 | 2012-09-11 | Bristol-Myers Squibb Company | 1,2,3-triazoles as 11-beta hydroxysteroid dehydrogenase type I inhibitors |
| EP2128158A1 (en) * | 2008-05-26 | 2009-12-02 | Phenex Pharmaceuticals AG | Heterocyclic cyclopropyl-substituted FXR binding compounds |
| CN102164899B (zh) | 2008-09-25 | 2014-11-26 | 霍夫曼-拉罗奇有限公司 | 用作抗异常脂肪血症及相关疾病的fxr调节剂的取代的吲唑或四氢吲唑类 |
| EP2289883A1 (en) | 2009-08-19 | 2011-03-02 | Phenex Pharmaceuticals AG | Novel FXR (NR1H4) binding and activity modulating compounds |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| US8252826B2 (en) | 2010-03-24 | 2012-08-28 | Hoffmann-La Roche Inc. | Cyclopentyl- and cycloheptylpyrazoles |
| US8933024B2 (en) | 2010-06-18 | 2015-01-13 | Sanofi | Azolopyridin-3-one derivatives as inhibitors of lipases and phospholipases |
| BR112013007651A2 (pt) | 2010-09-28 | 2019-09-24 | Bristol-Myers Squibb Company | análogos de piperazina com grupos heteroarila substituídos como antivirais de influenza de amplo espectro |
| BR112013011265A2 (pt) * | 2010-11-09 | 2016-11-01 | Hoffmann La Roche | derivados de triazol como ligantes para receptores gaba |
| US8742097B2 (en) * | 2010-11-09 | 2014-06-03 | Hoffmann-La Roche Inc. | Triazole compounds I |
| CU24152B1 (es) | 2010-12-20 | 2016-02-29 | Irm Llc | 1,2 oxazol-8-azabiciclo[3,2,1]octano 8 il como moduladores de fxr |
| US8828994B2 (en) | 2011-03-08 | 2014-09-09 | Sanofi | Di- and tri-substituted oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
| US8871758B2 (en) | 2011-03-08 | 2014-10-28 | Sanofi | Tetrasubstituted oxathiazine derivatives, method for producing them, their use as medicine and drug containing said derivatives and the use thereof |
| WO2012120053A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2766349B1 (de) | 2011-03-08 | 2016-06-01 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2012120055A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| IL253437A0 (en) * | 2011-07-13 | 2017-09-28 | Gilead Sciences Inc | New compounds modulate fxr (nr1h4) activity and bind |
| EP2545964A1 (en) * | 2011-07-13 | 2013-01-16 | Phenex Pharmaceuticals AG | Novel FXR (NR1H4) binding and activity modulating compounds |
| WO2013037482A1 (en) | 2011-09-15 | 2013-03-21 | Phenex Pharmaceuticals Ag | Farnesoid x receptor agonists for cancer treatment and prevention |
| JP6223443B2 (ja) * | 2012-06-26 | 2017-11-01 | サニオナ・エイピイエス | フェニルトリアゾール誘導体及びｇａｂａａ受容体複合体を調節するための該フェニルトリアゾール誘導体の使用 |
| PT3043865T (pt) | 2013-09-11 | 2021-01-14 | Univ Claude Bernard Lyon | Métodos e composições farmacêuticas para o tratamento da infeção por vírus da hepatite b |
| JP2017505770A (ja) | 2014-01-24 | 2017-02-23 | シンアフィックス ビー．ブイ． | （ヘテロ）アリール１，３−双極子化合物と（ヘテロ）シクロアルキンとの環化付加のためのプロセス |
| EP3006939A1 (en) | 2014-10-06 | 2016-04-13 | Gilead Sciences, Inc. | Histidine-rich Glycoprotein as a marker for hepatic Farnesoid X receptor activation |
| US10208081B2 (en) | 2014-11-26 | 2019-02-19 | Enanta Pharmaceuticals, Inc. | Bile acid derivatives as FXR/TGR5 agonists and methods of use thereof |
| MA41094A (fr) * | 2014-12-02 | 2017-10-10 | Lilly Co Eli | Procédés de traitement de troubles rénaux |
| EP3034499A1 (en) | 2014-12-17 | 2016-06-22 | Gilead Sciences, Inc. | Novel FXR (NR1H4) modulating compounds |
| EP3034501A1 (en) | 2014-12-17 | 2016-06-22 | Gilead Sciences, Inc. | Hydroxy containing FXR (NR1H4) modulating compounds |
| EA036404B1 (ru) | 2015-02-06 | 2020-11-06 | Интерсепт Фармасьютикалз, Инк. | Фармацевтические композиции для комбинированной терапии |
| TWI698430B (zh) | 2015-02-13 | 2020-07-11 | 南北兄弟藥業投資有限公司 | 三環化合物及其在藥物中的應用 |
| EA036757B1 (ru) | 2015-04-07 | 2020-12-17 | Интерсепт Фармасьютикалз, Инк. | Фармацевтические композиции для комбинированной терапии |
| WO2017218337A1 (en) | 2016-06-13 | 2017-12-21 | Gilead Sciences, Inc. | Fxr (nr1h4) modulating compounds |
| CA3252823A1 (en) | 2016-06-13 | 2025-02-25 | Gilead Sciences, Inc. | Fxr (nr1h4) modulating compounds |
| TW201808283A (zh) | 2016-08-05 | 2018-03-16 | 廣東東陽光藥業有限公司 | 含氮三環化合物及其在藥物中的應用 |
| KR20190117632A (ko) | 2017-02-21 | 2019-10-16 | 장피트 | Ppar 효현제와 fxr 효현제의 병용 |
| SI3600309T1 (sl) | 2017-03-28 | 2022-10-28 | Gilead Sciences, Inc. | Terapevtske kombinacije za zdravljenje bolezni jeter |
| JP2020515564A (ja) | 2017-03-30 | 2020-05-28 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | エピソーマルウイルスの持続性及び発現を低下させるための方法及び医薬組成物 |
| JP6886074B2 (ja) * | 2017-04-12 | 2021-06-16 | イルドン ファーマシューティカル カンパニー リミテッド | 核受容体の効能剤であるイソオキサゾール誘導体及びその用途 |
| ES2963652T3 (es) | 2017-11-01 | 2024-04-01 | Bristol Myers Squibb Co | Compuestos espirocíclicos de alquenos como moduladores del receptor x farnesoide |
| CN111278817B (zh) | 2017-11-01 | 2023-05-16 | 百时美施贵宝公司 | 作为法尼醇x受体调节剂的多环化合物 |
| WO2019089670A1 (en) | 2017-11-01 | 2019-05-09 | Bristol-Myers Squibb Company | Alkene compounds as farnesoid x receptor modulators |
| CN110128432B (zh) | 2018-02-02 | 2021-03-02 | 广东东阳光药业有限公司 | 含氮三环化合物及其在药物中的应用 |
| IT201800007265A1 (it) * | 2018-07-17 | 2020-01-17 | Isossazoli come agonisti del recettore fxr | |
| BR102019014802A2 (pt) | 2018-07-20 | 2020-02-04 | Boehringer Ingelheim Int | difluorometil-fenil triazóis |
| HU231223B1 (hu) | 2018-09-28 | 2022-01-28 | Richter Gedeon Nyrt. | GABAA A5 receptor modulátor hatású biciklusos vegyületek |
| WO2020150136A1 (en) | 2019-01-15 | 2020-07-23 | Gilead Sciences, Inc. | Fxr (nr1h4) modulating compounds |
| US11524005B2 (en) | 2019-02-19 | 2022-12-13 | Gilead Sciences, Inc. | Solid forms of FXR agonists |
| CA3142358A1 (en) | 2019-05-30 | 2020-12-03 | Intercept Pharmaceuticals, Inc. | Pharmaceutical compositions comprising a fxr agonist and a fibrate for use in the treatment of cholestatic liver disease |
| CA3139291A1 (en) | 2019-07-18 | 2021-01-21 | Jacky Vonderscher | Method for decreasing adverse-effects of interferon |
| WO2021108974A1 (en) | 2019-12-03 | 2021-06-10 | Gannex Pharma Co., Ltd | Compounds for modulating activity of fxr and uses thereof |
| CN110878052B (zh) * | 2019-12-11 | 2021-05-07 | 山东大学 | 一种含有fxr激动剂的化合物及其制备方法和应用 |
| ES3014367T3 (en) | 2020-01-15 | 2025-04-22 | Inst Nat Sante Rech Med | Use of fxr agonists for treating an infection by hepatitis d virus |
| US20240043418A1 (en) | 2020-03-26 | 2024-02-08 | Richter Gedeon Nyrt. | 1,3-dihydro-2h-pyrrolo[3,4-c]pyridine derivatives as gabaa a5 receptor modulators |
| CA3204800A1 (en) | 2021-01-14 | 2022-07-21 | Raphael Darteil | Synergistic effect of a fxr agonist and ifn for the treatment of hbv infection |
| JP2024517181A (ja) | 2021-04-28 | 2024-04-19 | ウエヌイグレックオ・ファーマ | 組合せ治療としてｆｘｒアゴニストを使用するｔｌｒ３アゴニストの効果の強い増強 |
| CN119710733B (zh) * | 2025-02-07 | 2025-09-30 | 青岛科技大学 | 一种吲哚-3-基烷基丙二酸酯类化合物的制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07138258A (ja) * | 1993-11-16 | 1995-05-30 | Taiho Yakuhin Kogyo Kk | チアゾリジンジオン誘導体又はその塩 |
| DE60131967D1 (de) * | 2001-08-13 | 2008-01-31 | Phenex Pharmaceuticals Ag | Nr1h4-kern-rezeptor-bindende verbindungen |
| AU2003290700A1 (en) | 2002-11-22 | 2004-06-18 | Smithkline Beecham Corporation | Farnesoid x receptor agonists |
| US7507832B2 (en) * | 2003-12-22 | 2009-03-24 | Eli Lilly And Company | Triazole PPAR modulators |
-
2007
- 2007-05-22 AR ARP070102216A patent/AR061101A1/es not_active Application Discontinuation
- 2007-05-22 US US12/298,769 patent/US8106077B2/en active Active
- 2007-05-22 BR BRPI0711875-9A patent/BRPI0711875A2/pt not_active IP Right Cessation
- 2007-05-22 WO PCT/US2007/069416 patent/WO2007140174A2/en not_active Ceased
- 2007-05-22 EA EA200870569A patent/EA014720B1/ru not_active IP Right Cessation
- 2007-05-22 AT AT07811915T patent/ATE460403T1/de not_active IP Right Cessation
- 2007-05-22 ES ES07811915T patent/ES2340221T3/es active Active
- 2007-05-22 AU AU2007267692A patent/AU2007267692B2/en not_active Ceased
- 2007-05-22 DE DE602007005256T patent/DE602007005256D1/de active Active
- 2007-05-22 PE PE2007000629A patent/PE20080259A1/es not_active Application Discontinuation
- 2007-05-22 MX MX2008014959A patent/MX2008014959A/es active IP Right Grant
- 2007-05-22 CA CA002651373A patent/CA2651373A1/en not_active Abandoned
- 2007-05-22 EP EP07811915A patent/EP2029558B1/en active Active
- 2007-05-22 TW TW096118230A patent/TW200812982A/zh unknown
- 2007-05-22 JP JP2009512254A patent/JP5225984B2/ja active Active
- 2007-05-22 CL CL2007001451A patent/CL2007001451A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MX2008014959A (es) | 2008-12-09 |
| PE20080259A1 (es) | 2008-04-10 |
| CL2007001451A1 (es) | 2008-01-11 |
| EA200870569A1 (ru) | 2009-06-30 |
| US20090093524A1 (en) | 2009-04-09 |
| EA014720B1 (ru) | 2011-02-28 |
| TW200812982A (en) | 2008-03-16 |
| EP2029558B1 (en) | 2010-03-10 |
| DE602007005256D1 (de) | 2010-04-22 |
| BRPI0711875A2 (pt) | 2012-01-10 |
| WO2007140174A2 (en) | 2007-12-06 |
| EP2029558A2 (en) | 2009-03-04 |
| JP2009538333A (ja) | 2009-11-05 |
| JP5225984B2 (ja) | 2013-07-03 |
| CA2651373A1 (en) | 2007-12-06 |
| WO2007140174A3 (en) | 2008-03-20 |
| AU2007267692A1 (en) | 2007-12-06 |
| US8106077B2 (en) | 2012-01-31 |
| AU2007267692B2 (en) | 2012-06-14 |
| ATE460403T1 (de) | 2010-03-15 |
| AR061101A1 (es) | 2008-08-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2340221T3 (es) | Compuestos y procedimientos para modular fxr. | |
| JP5119241B2 (ja) | Ｆｘｒアゴニスト | |
| KR101157334B1 (ko) | Ｆｘｒ을 조절하기 위한 화합물 및 방법 | |
| FI104072B (fi) | Menetelmä terapeuttisesti käyttökelpoisten N-(aryylioksialkyyli)heteroaryylipiperidiinien ja -heteroaryylipiperatsiinien valmistamiseksi | |
| ES2255294T3 (es) | Derivados de isoxazol sustituidos como moduladores del receptor de estrogenos. | |
| ES2516716T3 (es) | Compuesto de ácido carboxílico | |
| KR101819680B1 (ko) | 시그마 수용체 억제제로서의 피라졸 화합물 | |
| WO2005087710A1 (ja) | アミノフェニルプロパン酸誘導体 | |
| WO2004106276A1 (ja) | 縮合環化合物 | |
| CN119968377A (zh) | 氨基磷酸酯化合物及其用途 | |
| ES2342222T3 (es) | Agonistas de fxr. | |
| KR20010040254A (ko) | 아미노알킬페놀 유도체 및 관련 화합물 | |
| CN1918129B (zh) | 治疗剂 | |
| JPH0256452A (ja) | フェニルカルボン酸誘導体 |