MX2008014959A - Compuestos y metodos para modular fxr. - Google Patents
Compuestos y metodos para modular fxr.Info
- Publication number
- MX2008014959A MX2008014959A MX2008014959A MX2008014959A MX2008014959A MX 2008014959 A MX2008014959 A MX 2008014959A MX 2008014959 A MX2008014959 A MX 2008014959A MX 2008014959 A MX2008014959 A MX 2008014959A MX 2008014959 A MX2008014959 A MX 2008014959A
- Authority
- MX
- Mexico
- Prior art keywords
- methyl
- phenyl
- hydrogen
- isopropyl
- group
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 197
- 238000000034 method Methods 0.000 title claims abstract description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 16
- 208000032928 Dyslipidaemia Diseases 0.000 claims abstract description 15
- 208000017170 Lipid metabolism disease Diseases 0.000 claims abstract description 15
- 201000010099 disease Diseases 0.000 claims abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- -1 C1-C3 thiohaloalkyl Chemical group 0.000 claims description 214
- 229910052739 hydrogen Inorganic materials 0.000 claims description 127
- 239000001257 hydrogen Substances 0.000 claims description 123
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 67
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 56
- 239000002253 acid Substances 0.000 claims description 54
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 50
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 47
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 46
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 46
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 45
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 45
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
- 239000005711 Benzoic acid Substances 0.000 claims description 32
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 28
- 125000001153 fluoro group Chemical group F* 0.000 claims description 28
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 28
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 28
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 22
- 125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 0.000 claims description 21
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 18
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 18
- 125000001041 indolyl group Chemical group 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 125000001188 haloalkyl group Chemical group 0.000 claims description 17
- 125000005843 halogen group Chemical group 0.000 claims description 17
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 12
- 125000002541 furyl group Chemical group 0.000 claims description 11
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 11
- 125000000335 thiazolyl group Chemical group 0.000 claims description 11
- 125000001544 thienyl group Chemical group 0.000 claims description 11
- 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 claims description 10
- 239000000460 chlorine Chemical group 0.000 claims description 9
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 150000003626 triacylglycerols Chemical class 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Chemical group 0.000 claims description 5
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 201000001320 Atherosclerosis Diseases 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
- 206010012601 diabetes mellitus Diseases 0.000 claims description 4
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 4
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 3
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 3
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 238000008214 LDL Cholesterol Methods 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 230000001404 mediated effect Effects 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 25
- XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 claims 1
- 125000005037 alkyl phenyl group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 244
- 238000002360 preparation method Methods 0.000 description 144
- 238000006243 chemical reaction Methods 0.000 description 108
- 239000000243 solution Substances 0.000 description 108
- 235000019439 ethyl acetate Nutrition 0.000 description 98
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 94
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 91
- 150000004702 methyl esters Chemical class 0.000 description 83
- 239000011541 reaction mixture Substances 0.000 description 82
- 230000002829 reductive effect Effects 0.000 description 77
- 239000000203 mixture Substances 0.000 description 76
- 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 73
- 229910001868 water Inorganic materials 0.000 description 71
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 52
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 33
- 239000012267 brine Substances 0.000 description 33
- 239000012044 organic layer Substances 0.000 description 33
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 32
- 239000007787 solid Substances 0.000 description 31
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- 239000010410 layer Substances 0.000 description 29
- 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 28
- 101150041968 CDC13 gene Proteins 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 27
- 238000003818 flash chromatography Methods 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
- 239000007858 starting material Substances 0.000 description 26
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 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
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 16
- 235000019341 magnesium sulphate Nutrition 0.000 description 16
- 125000003944 tolyl group Chemical group 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 239000011734 sodium Substances 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 14
- 235000011152 sodium sulphate Nutrition 0.000 description 14
- 239000012074 organic phase Substances 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
- 235000012000 cholesterol Nutrition 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- 102100038495 Bile acid receptor Human genes 0.000 description 11
- 101000603876 Homo sapiens Bile acid receptor Proteins 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 239000000377 silicon dioxide Substances 0.000 description 11
- 229920002554 vinyl polymer Polymers 0.000 description 11
- 239000005909 Kieselgur Substances 0.000 description 10
- 229910052681 coesite Inorganic materials 0.000 description 10
- 229910052906 cristobalite Inorganic materials 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
- 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 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 125000004494 ethyl ester group Chemical group 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 8
- 102100023172 Nuclear receptor subfamily 0 group B member 2 Human genes 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
- 238000003756 stirring Methods 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
- 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 8
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 7
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-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
- 229910002091 carbon monoxide Inorganic materials 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 6
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 5
- OIWOOOJFKXTXKV-UHFFFAOYSA-N 4-formyl-2-methylbenzoic acid Chemical compound CC1=CC(C=O)=CC=C1C(O)=O OIWOOOJFKXTXKV-UHFFFAOYSA-N 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
- 229910000024 caesium carbonate Inorganic materials 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- 108020004999 messenger RNA Proteins 0.000 description 5
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 5
- 238000012360 testing method Methods 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 4
- GPOQODYGMUTOQL-UHFFFAOYSA-N 4-bromo-3-methylphenol Chemical compound CC1=CC(O)=CC=C1Br GPOQODYGMUTOQL-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 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 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 108010007622 LDL Lipoproteins Proteins 0.000 description 4
- 102000007330 LDL Lipoproteins Human genes 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 238000004440 column chromatography Methods 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
- 150000002148 esters Chemical class 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 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
- 238000000746 purification Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 235000010288 sodium nitrite Nutrition 0.000 description 4
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 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
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 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
- 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 3
- FGOJCPKOOGIRPA-UHFFFAOYSA-N 1-o-tert-butyl 4-o-ethyl 5-oxoazepane-1,4-dicarboxylate Chemical compound CCOC(=O)C1CCN(C(=O)OC(C)(C)C)CCC1=O FGOJCPKOOGIRPA-UHFFFAOYSA-N 0.000 description 3
- QNIRFRFJUNXYMH-UHFFFAOYSA-N 2-(2-trimethylsilylethynyl)benzoic acid Chemical compound C[Si](C)(C)C#CC1=CC=CC=C1C(O)=O QNIRFRFJUNXYMH-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-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
- 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
- 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
- 239000004215 Carbon black (E152) Substances 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
- 102000004895 Lipoproteins Human genes 0.000 description 3
- 108090001030 Lipoproteins Proteins 0.000 description 3
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 239000007832 Na2SO4 Substances 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 235000010357 aspartame Nutrition 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 125000004188 dichlorophenyl group Chemical group 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 229940121360 farnesoid X receptor (fxr) agonists Drugs 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 150000002430 hydrocarbons Chemical class 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
- 239000012139 lysis buffer Substances 0.000 description 3
- 239000000463 material Substances 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
- 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 3
- 102000006255 nuclear receptors Human genes 0.000 description 3
- 108020004017 nuclear receptors Proteins 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 102000004169 proteins and genes Human genes 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
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 3
- 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
- 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 2
- JDMFXJULNGEPOI-UHFFFAOYSA-N 2,6-dichloroaniline Chemical compound NC1=C(Cl)C=CC=C1Cl JDMFXJULNGEPOI-UHFFFAOYSA-N 0.000 description 2
- 125000004974 2-butenyl group Chemical group C(C=CC)* 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
- 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 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
- 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 2
- MNPLTKHJEAFOCA-UHFFFAOYSA-N 4-amino-3-fluorophenol Chemical compound NC1=CC=C(O)C=C1F MNPLTKHJEAFOCA-UHFFFAOYSA-N 0.000 description 2
- RVCJOGNLYVNRDN-UHFFFAOYSA-N 4-bromo-2-methylbenzoic acid Chemical compound CC1=CC(Br)=CC=C1C(O)=O RVCJOGNLYVNRDN-UHFFFAOYSA-N 0.000 description 2
- 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 2
- SJXHLZCPDZPBPW-UHFFFAOYSA-N 4-ethynylbenzoic acid Chemical compound OC(=O)C1=CC=C(C#C)C=C1 SJXHLZCPDZPBPW-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
- QGNGOGOOPUYKMC-UHFFFAOYSA-N 4-hydroxy-6-methylaniline Chemical compound CC1=CC(O)=CC=C1N QGNGOGOOPUYKMC-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
- 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
- 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 2
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 239000004606 Fillers/Extenders 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
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 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
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 2
- GZFJLAPPHFGTTE-UHFFFAOYSA-N OC1=CC(=C(C=C1)N(C)CC1=C(C(=O)O)C=CC=C1)C Chemical compound OC1=CC(=C(C=C1)N(C)CC1=C(C(=O)O)C=CC=C1)C GZFJLAPPHFGTTE-UHFFFAOYSA-N 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
- 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 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
- 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
- 230000004913 activation Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000007864 aqueous solution Substances 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
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000007853 buffer solution 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
- 230000008859 change Effects 0.000 description 2
- 208000029078 coronary artery disease Diseases 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
- 230000001627 detrimental effect Effects 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
- 239000003937 drug carrier Substances 0.000 description 2
- HFBUFVYPHLRXGE-UHFFFAOYSA-N ethyl 3-(2,6-dichlorophenyl)-5-(trifluoromethyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=C(C(F)(F)F)N=NN1C1=C(Cl)C=CC=C1Cl HFBUFVYPHLRXGE-UHFFFAOYSA-N 0.000 description 2
- 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 2
- SFDRHPQGYUYYNX-UHFFFAOYSA-N ethyl 4,4,4-trifluorobut-2-ynoate Chemical compound CCOC(=O)C#CC(F)(F)F SFDRHPQGYUYYNX-UHFFFAOYSA-N 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
- 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
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 108010022197 lipoprotein cholesterol Proteins 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 2
- DSYLZQPIJVFYBP-UHFFFAOYSA-N methyl 2-butoxy-4-(hydroxymethyl)benzoate Chemical compound CCCCOC1=CC(CO)=CC=C1C(=O)OC DSYLZQPIJVFYBP-UHFFFAOYSA-N 0.000 description 2
- FSQOQFQTZISUJL-UHFFFAOYSA-N methyl 2-butoxy-4-methylbenzoate Chemical compound CCCCOC1=CC(C)=CC=C1C(=O)OC FSQOQFQTZISUJL-UHFFFAOYSA-N 0.000 description 2
- JTOJTFMOZMCZKU-UHFFFAOYSA-N methyl 4-(bromomethyl)-2-butoxybenzoate Chemical compound CCCCOC1=CC(CBr)=CC=C1C(=O)OC JTOJTFMOZMCZKU-UHFFFAOYSA-N 0.000 description 2
- DSCDSFHUSZSPLM-UHFFFAOYSA-N methyl 4-(hydroxymethyl)-2-methylbenzoate Chemical compound COC(=O)C1=CC=C(CO)C=C1C DSCDSFHUSZSPLM-UHFFFAOYSA-N 0.000 description 2
- 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 2
- ZCPCZELMTZDPAK-UHFFFAOYSA-N methyl 5-(4-hydroxy-2-methylphenyl)-4-methylthiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC(C)=C1C1=CC=C(O)C=C1C ZCPCZELMTZDPAK-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
- 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 2
- 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 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
- 230000001590 oxidative effect Effects 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
- 239000012071 phase Substances 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 229910052701 rubidium Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 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
- 238000007920 subcutaneous administration Methods 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
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 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
- 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 2
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 2
- VJVZPTPOYCJFNI-UHFFFAOYSA-M (2-ethoxy-2-oxoethyl)-triphenylphosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CC(=O)OCC)C1=CC=CC=C1 VJVZPTPOYCJFNI-UHFFFAOYSA-M 0.000 description 1
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- GKVHYRRQQVUDKB-UHFFFAOYSA-N (4-iodo-3-methylphenyl)methanol Chemical compound CC1=CC(CO)=CC=C1I GKVHYRRQQVUDKB-UHFFFAOYSA-N 0.000 description 1
- 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
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
- VMSLCPKYRPDHLN-UHFFFAOYSA-N (R)-Humulone Chemical compound CC(C)CC(=O)C1=C(O)C(CC=C(C)C)=C(O)C(O)(CC=C(C)C)C1=O VMSLCPKYRPDHLN-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
- 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
- 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
- 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
- BHXVYTQDWMQVBI-UHFFFAOYSA-N 1h-indazole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=NNC2=C1 BHXVYTQDWMQVBI-UHFFFAOYSA-N 0.000 description 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
- NIBFJPXGNVPNHK-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-4-carbaldehyde Chemical group C1=CC(C=O)=C2OC(F)(F)OC2=C1 NIBFJPXGNVPNHK-UHFFFAOYSA-N 0.000 description 1
- QUCMZSJETXEAMC-UHFFFAOYSA-N 2-(2-sulfanylphenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1S QUCMZSJETXEAMC-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
- 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
- IOSGANIYBODQTB-UHFFFAOYSA-N 2-ethynylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C#C IOSGANIYBODQTB-UHFFFAOYSA-N 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 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
- 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 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
- HVFJDDIMHALNJE-UHFFFAOYSA-N 3-(2-trimethylsilylethynyl)benzoic acid Chemical compound C[Si](C)(C)C#CC1=CC=CC(C(O)=O)=C1 HVFJDDIMHALNJE-UHFFFAOYSA-N 0.000 description 1
- 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 1
- ZVXYNUPQYOMXFM-UHFFFAOYSA-N 3-[2-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]-2-methylphenyl]ethenyl]benzoic acid Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC(C=C1C)=CC=C1C=CC1=CC=CC(C(O)=O)=C1 ZVXYNUPQYOMXFM-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
- PHPIMLZTBYCDSX-UHFFFAOYSA-N 3-ethynylbenzoic acid Chemical compound OC(=O)C1=CC=CC(C#C)=C1 PHPIMLZTBYCDSX-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
- ITLWSYAJGXPQSO-UHFFFAOYSA-N 3-methyl-4-phenylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC=C1C1=CC=CC=C1 ITLWSYAJGXPQSO-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
- ZVGCJDPEKKEYES-UHFFFAOYSA-N 3-trimethylsilylprop-2-yn-1-ol Chemical compound C[Si](C)(C)C#CCO ZVGCJDPEKKEYES-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
- 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
- UQRRADWBGZXPLQ-UHFFFAOYSA-N 4-(2-chloro-4-hydroxyphenyl)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=C(O)C=C1Cl UQRRADWBGZXPLQ-UHFFFAOYSA-N 0.000 description 1
- BFZOGYLGSYAMAE-UHFFFAOYSA-N 4-(2-fluoro-4-hydroxyphenyl)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=C(O)C=C1F BFZOGYLGSYAMAE-UHFFFAOYSA-N 0.000 description 1
- SLKZDWAZOKIEEU-UHFFFAOYSA-N 4-(2-fluorophenyl)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=CC=C1F SLKZDWAZOKIEEU-UHFFFAOYSA-N 0.000 description 1
- XKGFCCZEXVIRQH-UHFFFAOYSA-N 4-(2-nitrophenyl)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=CC=C1[N+]([O-])=O XKGFCCZEXVIRQH-UHFFFAOYSA-N 0.000 description 1
- CVFLWXCNPWFJEH-UHFFFAOYSA-N 4-(3-methylphenyl)benzoic acid Chemical compound CC1=CC=CC(C=2C=CC(=CC=2)C(O)=O)=C1 CVFLWXCNPWFJEH-UHFFFAOYSA-N 0.000 description 1
- XMTQOHCLMOKJEV-UHFFFAOYSA-N 4-(4-hydroxy-3-methylphenyl)benzoic acid Chemical compound C1=C(O)C(C)=CC(C=2C=CC(=CC=2)C(O)=O)=C1 XMTQOHCLMOKJEV-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
- 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 1
- MDHXDWFVPXGYJF-UHFFFAOYSA-N 4-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]phenyl]benzamide Chemical compound CC(C)C=1N=NN(C=2C(=CC=CC=2Cl)Cl)C=1COC(C=C1)=CC=C1C1=CC=C(C(N)=O)C=C1 MDHXDWFVPXGYJF-UHFFFAOYSA-N 0.000 description 1
- MGJDQVSIZMWDKE-UHFFFAOYSA-N 4-amino-3-(trifluoromethyl)benzoic acid 4-iodo-3-(trifluoromethyl)benzoic acid Chemical compound NC1=C(C=C(C(=O)O)C=C1)C(F)(F)F.IC1=C(C=C(C(=O)O)C=C1)C(F)(F)F MGJDQVSIZMWDKE-UHFFFAOYSA-N 0.000 description 1
- BPPJOHSPAQNDML-UHFFFAOYSA-N 4-formyl-2-(trifluoromethyl)benzoic acid Chemical compound C(=O)C1=CC(=C(C(=O)O)C=C1)C(F)(F)F BPPJOHSPAQNDML-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
- DKMIWBBIVNNAMG-UHFFFAOYSA-N 4-iodo-3-methylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC=C1I DKMIWBBIVNNAMG-UHFFFAOYSA-N 0.000 description 1
- RQIRASYNLSFTIG-UHFFFAOYSA-N 4-methylpent-2-ynoic acid Chemical compound CC(C)C#CC(O)=O RQIRASYNLSFTIG-UHFFFAOYSA-N 0.000 description 1
- 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 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
- SZVUEGIULUFQQG-UHFFFAOYSA-N 6-bromo-1-propan-2-ylindole-3-carboxylic acid Chemical compound C1=C(Br)C=C2N(C(C)C)C=C(C(O)=O)C2=C1 SZVUEGIULUFQQG-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
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- FWEOQOXTVHGIFQ-UHFFFAOYSA-N 8-anilinonaphthalene-1-sulfonic acid Chemical compound C=12C(S(=O)(=O)O)=CC=CC2=CC=CC=1NC1=CC=CC=C1 FWEOQOXTVHGIFQ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- 229910015845 BBr3 Inorganic materials 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
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 206010008635 Cholestasis Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 238000010485 C−C bond formation reaction Methods 0.000 description 1
- 230000004568 DNA-binding Effects 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
- 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
- 108010001831 LDL receptors Proteins 0.000 description 1
- 102000000853 LDL receptors Human genes 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 1
- CQCWMIPTARNZMO-UHFFFAOYSA-N NC=1C(=CC(=CC1)O)C.COC(C1=C(C=C(C=C1)CNC1=C(C=C(C=C1)O)C)C)=O Chemical compound NC=1C(=CC(=CC1)O)C.COC(C1=C(C=C(C=C1)CNC1=C(C=C(C=C1)O)C)C)=O CQCWMIPTARNZMO-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-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
- 208000006011 Stroke Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- 108010069201 VLDL Cholesterol Proteins 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
- 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
- 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 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
- 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
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229910045601 alloy Inorganic materials 0.000 description 1
- 239000000956 alloy Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 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
- 239000003613 bile acid Substances 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 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
- 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
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 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
- 239000012501 chromatography medium Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 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
- 230000003247 decreasing effect 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
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229940117389 dichlorobenzene Drugs 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
- 239000006185 dispersion Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000003821 enantio-separation 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
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-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
- VYXQGOIIOVRLKW-UHFFFAOYSA-N ethyl 4-methylpent-2-ynoate Chemical compound CCOC(=O)C#CC(C)C VYXQGOIIOVRLKW-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
- QFXZANXYUCUTQH-UHFFFAOYSA-N ethynol Chemical group OC#C QFXZANXYUCUTQH-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
- 238000011049 filling Methods 0.000 description 1
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229910000856 hastalloy Inorganic materials 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000002163 immunogen Effects 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
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 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
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000007937 lozenge Substances 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
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-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
- USOHUXMHLGFRHW-UHFFFAOYSA-N methyl 2-(4-hydroxyphenyl)-1-benzothiophene-6-carboxylate Chemical compound S1C2=CC(C(=O)OC)=CC=C2C=C1C1=CC=C(O)C=C1 USOHUXMHLGFRHW-UHFFFAOYSA-N 0.000 description 1
- RZIFWMFGIZWKOL-UHFFFAOYSA-N methyl 2-(4-methoxyphenyl)benzoate Chemical compound COC(=O)C1=CC=CC=C1C1=CC=C(OC)C=C1 RZIFWMFGIZWKOL-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
- LBMDZNOARBBHHG-UHFFFAOYSA-N methyl 2-ethynylbenzoate Chemical compound COC(=O)C1=CC=CC=C1C#C LBMDZNOARBBHHG-UHFFFAOYSA-N 0.000 description 1
- UITFCFWKYAOJEJ-UHFFFAOYSA-N methyl 2-hydroxy-4-methylbenzoate Chemical compound COC(=O)C1=CC=C(C)C=C1O UITFCFWKYAOJEJ-UHFFFAOYSA-N 0.000 description 1
- BXXLTVBTDZXPTN-UHFFFAOYSA-N methyl 2-iodobenzoate Chemical compound COC(=O)C1=CC=CC=C1I BXXLTVBTDZXPTN-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
- OYDOFGBVULDGDS-UHFFFAOYSA-N methyl 3-(diethoxyphosphorylmethyl)benzoate Chemical compound CCOP(=O)(OCC)CC1=CC=CC(C(=O)OC)=C1 OYDOFGBVULDGDS-UHFFFAOYSA-N 0.000 description 1
- SVKLHAXESBIPNF-UHFFFAOYSA-N methyl 3-[2-(2-chloro-4-hydroxyphenyl)ethenyl]benzoate Chemical compound COC(=O)C1=CC=CC(C=CC=2C(=CC(O)=CC=2)Cl)=C1 SVKLHAXESBIPNF-UHFFFAOYSA-N 0.000 description 1
- IHXVDUQOHZEJLU-UHFFFAOYSA-N methyl 3-[2-(4-hydroxy-2-methylphenyl)ethenyl]benzoate Chemical compound COC(=O)C1=CC=CC(C=CC=2C(=CC(O)=CC=2)C)=C1 IHXVDUQOHZEJLU-UHFFFAOYSA-N 0.000 description 1
- MBKUHNGECMPIHH-UHFFFAOYSA-N methyl 3-ethenylbenzoate Chemical compound COC(=O)C1=CC=CC(C=C)=C1 MBKUHNGECMPIHH-UHFFFAOYSA-N 0.000 description 1
- SJVMXEXEYBEEHK-UHFFFAOYSA-N methyl 4-(2-bromo-4-methoxyphenyl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=C(OC)C=C1Br SJVMXEXEYBEEHK-UHFFFAOYSA-N 0.000 description 1
- AVSYCCCSEGFTDG-UHFFFAOYSA-N methyl 4-(4-hydroxy-2-methylphenyl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=C(O)C=C1C AVSYCCCSEGFTDG-UHFFFAOYSA-N 0.000 description 1
- NLWBJPPMPLPZIE-UHFFFAOYSA-N methyl 4-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CBr)C=C1 NLWBJPPMPLPZIE-UHFFFAOYSA-N 0.000 description 1
- GNEADNFRBXZVDG-UHFFFAOYSA-N methyl 4-[(2-fluoro-4-hydroxyanilino)methyl]-2-methylbenzoate Chemical compound C1=C(C)C(C(=O)OC)=CC=C1CNC1=CC=C(O)C=C1F GNEADNFRBXZVDG-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
- 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 1
- CYEXEOXALMJXDI-UHFFFAOYSA-N methyl 4-bromo-2-methylbenzoate Chemical compound COC(=O)C1=CC=C(Br)C=C1C CYEXEOXALMJXDI-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
- AALWVKQRLXHHRT-UHFFFAOYSA-N methyl 5-(4-methoxy-2-methylphenyl)-4-methylthiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC(C)=C1C1=CC=C(OC)C=C1C AALWVKQRLXHHRT-UHFFFAOYSA-N 0.000 description 1
- MFOKOKHNSVUKON-UHFFFAOYSA-N methyl 5-bromo-1h-indole-3-carboxylate Chemical compound C1=C(Br)C=C2C(C(=O)OC)=CNC2=C1 MFOKOKHNSVUKON-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
- SKWDVGYXADERFY-UHFFFAOYSA-N methyl 6-(4-hydroxy-2-methylphenyl)-1-propan-2-ylindazole-3-carboxylate Chemical compound C=1C=C2C(C(=O)OC)=NN(C(C)C)C2=CC=1C1=CC=C(O)C=C1C SKWDVGYXADERFY-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
- VPDDVKPIOCFHRM-UHFFFAOYSA-N methyl 6-bromo-1-benzothiophene-3-carboxylate Chemical compound BrC1=CC=C2C(C(=O)OC)=CSC2=C1 VPDDVKPIOCFHRM-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
- 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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 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
- 150000002978 peroxides Chemical class 0.000 description 1
- CTRLRINCMYICJO-UHFFFAOYSA-N phenyl azide Chemical compound [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
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 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
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000013014 purified material Substances 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
- 239000000376 reactant Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 102000027483 retinoid hormone receptors Human genes 0.000 description 1
- 108091008679 retinoid hormone receptors Proteins 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
- 101150096065 shp gene Proteins 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000003871 sulfonates Chemical class 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
- 239000003826 tablet Substances 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
- 238000011285 therapeutic regimen Methods 0.000 description 1
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Substances ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 1
- 102000004217 thyroid hormone receptors Human genes 0.000 description 1
- 108090000721 thyroid hormone receptors Proteins 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 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
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000012546 transfer Methods 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
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 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
- 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 (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US80810406P | 2006-05-24 | 2006-05-24 | |
| US87000106P | 2006-12-14 | 2006-12-14 | |
| PCT/US2007/069416 WO2007140174A2 (en) | 2006-05-24 | 2007-05-22 | Compounds and methods for modulating fxr |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2008014959A true MX2008014959A (es) | 2008-12-09 |
Family
ID=38626336
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2008014959A MX2008014959A (es) | 2006-05-24 | 2007-05-22 | Compuestos y metodos 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 |
| US8217064B2 (en) | 2007-12-20 | 2012-07-10 | Envivo Pharmaceuticals, Inc. | Tetrasubstituted benzenes |
| 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 |
| MX2011002794A (es) * | 2008-09-25 | 2011-04-05 | Hoffmann La Roche | Indazol 2,3-sustituido o 4,5,6,7-tetrahidro-indazol como moduladores fxr contra dislipidemia y enfermedades relacionadas. |
| 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 |
| EP2582709B1 (de) | 2010-06-18 | 2018-01-24 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
| EA201390476A1 (ru) | 2010-09-28 | 2013-08-30 | Бристол-Майерс Сквибб Компани | Новые пиперазиновые аналоги с замещенными гетероарильными группами в качестве противовирусных средств широкого применения против гриппа |
| WO2012062623A1 (en) * | 2010-11-09 | 2012-05-18 | F. Hoffmann-La Roche Ag | Triazole derivatives as ligands for gaba receptors |
| 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 |
| EP2683705B1 (de) | 2011-03-08 | 2015-04-22 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| 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 |
| EP2683704B1 (de) | 2011-03-08 | 2014-12-17 | Sanofi | Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| US8710050B2 (en) | 2011-03-08 | 2014-04-29 | Sanofi | Di and tri- substituted oxathiazine derivatives, method for the production, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
| WO2012120052A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2545964A1 (en) * | 2011-07-13 | 2013-01-16 | Phenex Pharmaceuticals AG | Novel FXR (NR1H4) binding and activity modulating compounds |
| IL253437A0 (en) * | 2011-07-13 | 2017-09-28 | Gilead Sciences Inc | New compounds modulate fxr (nr1h4) activity and bind |
| WO2013037482A1 (en) | 2011-09-15 | 2013-03-21 | Phenex Pharmaceuticals Ag | Farnesoid x receptor agonists for cancer treatment and prevention |
| BR112014032501A2 (pt) * | 2012-06-26 | 2017-06-27 | Saniona Aps | composto, e, composição farmacêutica. |
| DK3043865T3 (da) | 2013-09-11 | 2021-02-01 | Univ Claude Bernard Lyon | Fremgangsmåder og farmaceutiske sammensætningr til behandlingen af hepatitis b-virusinfektion |
| US11168085B2 (en) | 2014-01-24 | 2021-11-09 | Synaffix B.V. | Process for the cycloaddition of a hetero(aryl) 1,3-dipole compound with a (hetero)cycloalkyne |
| 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 |
| CN107405325B (zh) | 2015-02-06 | 2021-11-12 | 英特塞普特医药品公司 | 用于组合疗法的药物组合物 |
| 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 |
| AU2016246524B2 (en) | 2015-04-07 | 2021-04-01 | Intercept Pharmaceuticals, Inc. | Pharmaceutical compositions for combination therapy |
| CA2968836C (en) | 2016-06-13 | 2025-09-02 | Gilead Sciences, Inc. | FXR MODULATING COMPOUNDS (NR1H4) |
| EP3468962A1 (en) | 2016-06-13 | 2019-04-17 | 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 |
| JP7618384B2 (ja) | 2017-02-21 | 2025-01-21 | ジェンフィ | Ｐｐａｒアゴニストとｆｘｒアゴニストとの組合せ |
| EP4424364A3 (en) | 2017-03-28 | 2024-11-27 | Gilead Sciences, Inc. | Methods of treating liver disease |
| US20210085662A1 (en) | 2017-03-30 | 2021-03-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for reducing persistence and expression of episomal viruses |
| PT3612520T (pt) * | 2017-04-12 | 2022-01-06 | Il Dong Pharma | Derivados de isoxazol como agonistas de recetores nucleares e utilizações dos mesmos |
| WO2019089665A1 (en) | 2017-11-01 | 2019-05-09 | Bristol-Myers Squibb Company | Alkene spirocyclic compounds as farnesoid x receptor modulators |
| 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 |
| ES2944657T3 (es) | 2017-11-01 | 2023-06-23 | Bristol Myers Squibb Co | Compuestos de alqueno como moduladores del receptor farnesoide X |
| 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 |
| AU2020209564B2 (en) | 2019-01-15 | 2022-12-01 | Gilead Sciences, Inc. | FXR (NR1H4) modulating compounds |
| CN118388474A (zh) | 2019-02-19 | 2024-07-26 | 吉利德科学公司 | Fxr激动剂的固体形式 |
| 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 |
| KR20220035365A (ko) | 2019-07-18 | 2022-03-22 | 엔요 파마 | 인터페론의 부작용을 감소시키는 방법 |
| 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 |
| CN114945361A (zh) | 2020-01-15 | 2022-08-26 | 法国国家卫生及研究医学协会 | Fxr激动剂在治疗丁型肝炎病毒感染中的用途 |
| EP4126858A1 (en) | 2020-03-26 | 2023-02-08 | Richter Gedeon Nyrt. | Dihydro-2-pyrrolo[3,4-c]pyridine derivatives as gabaa a5 receptor modulators |
| AU2022209084A1 (en) | 2021-01-14 | 2023-08-10 | Centre Leon Bérard | Synergistic effect of a fxr agonist and ifn for the treatment of hbv infection |
| WO2022229302A1 (en) | 2021-04-28 | 2022-11-03 | Enyo Pharma | Strong potentiation of tlr3 agonists effects using fxr agonists as a combined treatment |
| 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 |
| EP1285914B1 (en) | 2001-08-13 | 2007-12-19 | PheneX Pharmaceuticals AG | Nr1h4 nuclear receptor binding compounds |
| US7319109B2 (en) * | 2002-11-22 | 2008-01-15 | Smith Kline Beecham Corporation | Farnesoid X receptor agonists |
| AU2004311909A1 (en) * | 2003-12-22 | 2005-07-21 | Eli Lilly And Company | Triazole, oxadiazole and thiadiazole derivative as PPAR modulators for the treatment of diabetes |
-
2007
- 2007-05-22 EP EP07811915A patent/EP2029558B1/en active Active
- 2007-05-22 PE PE2007000629A patent/PE20080259A1/es not_active Application Discontinuation
- 2007-05-22 CA CA002651373A patent/CA2651373A1/en not_active Abandoned
- 2007-05-22 WO PCT/US2007/069416 patent/WO2007140174A2/en not_active Ceased
- 2007-05-22 AR ARP070102216A patent/AR061101A1/es not_active Application Discontinuation
- 2007-05-22 ES ES07811915T patent/ES2340221T3/es active Active
- 2007-05-22 CL CL2007001451A patent/CL2007001451A1/es unknown
- 2007-05-22 AT AT07811915T patent/ATE460403T1/de not_active IP Right Cessation
- 2007-05-22 BR BRPI0711875-9A patent/BRPI0711875A2/pt not_active IP Right Cessation
- 2007-05-22 AU AU2007267692A patent/AU2007267692B2/en not_active Ceased
- 2007-05-22 MX MX2008014959A patent/MX2008014959A/es active IP Right Grant
- 2007-05-22 EA EA200870569A patent/EA014720B1/ru not_active IP Right Cessation
- 2007-05-22 JP JP2009512254A patent/JP5225984B2/ja active Active
- 2007-05-22 US US12/298,769 patent/US8106077B2/en active Active
- 2007-05-22 TW TW096118230A patent/TW200812982A/zh unknown
- 2007-05-22 DE DE602007005256T patent/DE602007005256D1/de active Active
Also Published As
| Publication number | Publication date |
|---|---|
| AU2007267692A1 (en) | 2007-12-06 |
| CL2007001451A1 (es) | 2008-01-11 |
| CA2651373A1 (en) | 2007-12-06 |
| EP2029558A2 (en) | 2009-03-04 |
| JP2009538333A (ja) | 2009-11-05 |
| ES2340221T3 (es) | 2010-05-31 |
| TW200812982A (en) | 2008-03-16 |
| US20090093524A1 (en) | 2009-04-09 |
| JP5225984B2 (ja) | 2013-07-03 |
| EA200870569A1 (ru) | 2009-06-30 |
| WO2007140174A2 (en) | 2007-12-06 |
| AR061101A1 (es) | 2008-08-06 |
| BRPI0711875A2 (pt) | 2012-01-10 |
| PE20080259A1 (es) | 2008-04-10 |
| US8106077B2 (en) | 2012-01-31 |
| DE602007005256D1 (de) | 2010-04-22 |
| AU2007267692B2 (en) | 2012-06-14 |
| ATE460403T1 (de) | 2010-03-15 |
| WO2007140174A3 (en) | 2008-03-20 |
| EA014720B1 (ru) | 2011-02-28 |
| EP2029558B1 (en) | 2010-03-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| MX2008014959A (es) | Compuestos y metodos para modular fxr. | |
| CA2651378C (en) | Fxr agonists | |
| KR101157334B1 (ko) | Ｆｘｒ을 조절하기 위한 화합물 및 방법 | |
| KR101712466B1 (ko) | 신규의 에프엑스알(엔알 1에이치4) 결합 및 활성 조절 화합물 | |
| JP3816922B2 (ja) | Ｐｐａｒ活性を調節する化合物、及び該化合物の製造方法 | |
| RU2627703C2 (ru) | Агонисты gpr40 | |
| WO2004106276A1 (ja) | 縮合環化合物 | |
| AU2008229701A1 (en) | Pyrazole derivatives, compositions containing such compounds and methods of use | |
| US20170044147A1 (en) | Gpr40 agonists for the treatment of type ii diabetes | |
| US20170044146A1 (en) | Gpr40 agonists for the treatment of type ii diabetes | |
| JP4733692B2 (ja) | Ｐｐａｒ活性化剤としてのピラゾールフェニル誘導体 | |
| EP1740531A1 (en) | Indene derivatives and process for the preparation thereof | |
| ES2342222T3 (es) | Agonistas de fxr. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FG | Grant or registration |