BRPI0707427A2 - composto ou um sal farmaceuticamente aceitável do mesmo, método para tratar dislipidemia, aterosclerose, e diabetes e complicações da mesma, para elevar os nìveis plásmicos de hdl, e para diminuir triglicerìdeos plásmicos, composição farmacêutica, e, uso de um composto ou de um sal farmaceuticamente aceitável do mesmo - Google Patents

Info

Publication number

BRPI0707427A2

BRPI0707427A2 BRPI0707427-1A BRPI0707427A BRPI0707427A2 BR PI0707427 A2 BRPI0707427 A2 BR PI0707427A2 BR PI0707427 A BRPI0707427 A BR PI0707427A BR PI0707427 A2 BRPI0707427 A2 BR PI0707427A2

Authority

BR

Brazil

Prior art keywords

phenyl

methyl

carboxylic acid

isoxazol

ylmethoxy

Prior art date

2006-02-03

Links

• Espacenet
• Global Dossier
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• 150000001875 compounds Chemical class 0.000 title claims abstract description 226
• 238000000034 method Methods 0.000 title claims abstract description 28
• 150000003839 salts Chemical class 0.000 title claims abstract description 25
• 208000032928 Dyslipidaemia Diseases 0.000 title claims abstract description 13
• 208000017170 Lipid metabolism disease Diseases 0.000 title claims abstract description 13
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 6
• 206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 5
• 201000001320 Atherosclerosis Diseases 0.000 title claims description 6
• 150000003626 triacylglycerols Chemical class 0.000 title claims description 5
• 230000036470 plasma concentration Effects 0.000 title claims 2
• 238000002360 preparation method Methods 0.000 claims description 115
• YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Substances ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 112
• -1 C 1 -C 6 alkoxy Chemical group 0.000 claims description 107
• 239000002253 acid Substances 0.000 claims description 35
• 229910052739 hydrogen Inorganic materials 0.000 claims description 35
• 239000001257 hydrogen Substances 0.000 claims description 33
• 239000000460 chlorine Substances 0.000 claims description 27
• 150000002431 hydrogen Chemical class 0.000 claims description 18
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
• 125000000217 alkyl group Chemical group 0.000 claims description 14
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
• 229910052801 chlorine Inorganic materials 0.000 claims description 12
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
• 239000011737 fluorine Substances 0.000 claims description 9
• 229910052731 fluorine Inorganic materials 0.000 claims description 9
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
• 125000001041 indolyl group Chemical group 0.000 claims description 8
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
• 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 7
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
• 125000000335 thiazolyl group Chemical group 0.000 claims description 7
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 7
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
• 125000001544 thienyl group Chemical group 0.000 claims description 6
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 4
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 4
• 239000003814 drug Substances 0.000 claims description 4
• 230000001404 mediated effect Effects 0.000 claims description 4
• ZVTQYRVARPYRRE-UHFFFAOYSA-N oxadiazol-4-one Chemical compound O=C1CON=N1 ZVTQYRVARPYRRE-UHFFFAOYSA-N 0.000 claims description 4
• XWDMAGXYQPWSDN-UHFFFAOYSA-N 6-[4-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-1-benzothiophene-3-carboxylic acid Chemical compound C=1C=C(C=2C=C3SC=C(C3=CC=2)C(O)=O)C(C)=CC=1OCC1=C(C2CC2)ON=C1C1=CC=CC=C1OC(F)(F)F XWDMAGXYQPWSDN-UHFFFAOYSA-N 0.000 claims description 3
• 238000008214 LDL Cholesterol Methods 0.000 claims description 3
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
• YNVOMSDITJMNET-UHFFFAOYSA-N thiophene-3-carboxylic acid Chemical compound OC(=O)C=1C=CSC=1 YNVOMSDITJMNET-UHFFFAOYSA-N 0.000 claims description 3
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 2
• 239000005977 Ethylene Substances 0.000 claims description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 239000003085 diluting agent Substances 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• XWMXMWHHTIEXRE-UHFFFAOYSA-N thiadiazole 1-oxide Chemical compound O=S1C=CN=N1 XWMXMWHHTIEXRE-UHFFFAOYSA-N 0.000 claims description 2
• 125000001475 halogen functional group Chemical group 0.000 claims 3
• ZZIKYOSVNOPNQR-UHFFFAOYSA-N 6-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]-1-propan-2-ylindazole-3-carboxylic acid Chemical compound C=1C=C(C=2C=C3N(C(C)C)N=C(C3=CC=2)C(O)=O)C=CC=1OCC1=C(C(C)C)ON=C1C1=C(Cl)C=CC=C1Cl ZZIKYOSVNOPNQR-UHFFFAOYSA-N 0.000 claims 2
• OVVDFORZEGKEJM-UHFFFAOYSA-N 1-methylindazole-3-carboxylic acid Chemical compound C1=CC=C2N(C)N=C(C(O)=O)C2=C1 OVVDFORZEGKEJM-UHFFFAOYSA-N 0.000 claims 1
• FVELTSYVRUDGOY-UHFFFAOYSA-N 2-[4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-4-propan-2-yl-1,3-thiazole-5-carboxylic acid Chemical compound S1C(C(O)=O)=C(C(C)C)N=C1C(C(=C1)C)=CC=C1OCC1=C(C2CC2)ON=C1C1=C(Cl)C=CC=C1Cl FVELTSYVRUDGOY-UHFFFAOYSA-N 0.000 claims 1
• WTVHUEAULKJHLB-UHFFFAOYSA-N 2-[4-[[5-cyclopropyl-3-[2-fluoro-6-(trifluoromethyl)phenyl]-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-4-methyl-1,3-thiazole-5-carboxylic acid Chemical compound S1C(C(O)=O)=C(C)N=C1C(C(=C1)C)=CC=C1OCC1=C(C2CC2)ON=C1C1=C(F)C=CC=C1C(F)(F)F WTVHUEAULKJHLB-UHFFFAOYSA-N 0.000 claims 1
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 1
• SSOKAWOHMOSIJQ-UHFFFAOYSA-N 4-methyl-2-[2-methyl-4-[[5-propan-2-yl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]phenyl]-1,3-thiazole-5-carboxylic acid Chemical compound CC(C)C=1ON=C(C=2C(=CC=CC=2)OC(F)(F)F)C=1COC(C=C1C)=CC=C1C1=NC(C)=C(C(O)=O)S1 SSOKAWOHMOSIJQ-UHFFFAOYSA-N 0.000 claims 1
• QWJGNTHOQWQFFL-UHFFFAOYSA-N 5-[4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-4-methylthiophene-2-carboxylic acid Chemical compound C1=C(C(O)=O)SC(C=2C(=CC(OCC=3C(=NOC=3C3CC3)C=3C(=CC=CC=3Cl)Cl)=CC=2)C)=C1C QWJGNTHOQWQFFL-UHFFFAOYSA-N 0.000 claims 1
• BYKHFMZYLWYZSF-UHFFFAOYSA-N 6-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-2-methyl-1-propan-2-ylindole-3-carboxylic acid Chemical compound C=1C=C(C=2C=C3N(C(C)C)C(C)=C(C(O)=O)C3=CC=2)C(C)=CC=1OCC1=C(C(C)C)ON=C1C1=C(Cl)C=CC=C1Cl BYKHFMZYLWYZSF-UHFFFAOYSA-N 0.000 claims 1
• RBASMHPZQAJQJT-UHFFFAOYSA-N 6-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]-1-methylindazole-3-carboxylic acid Chemical compound C=1C=C(C=2C=C3N(C)N=C(C3=CC=2)C(O)=O)C=CC=1OCC1=C(C(C)C)ON=C1C1=C(Cl)C=CC=C1Cl RBASMHPZQAJQJT-UHFFFAOYSA-N 0.000 claims 1
• KZSBGQYBMRPUGK-UHFFFAOYSA-N 6-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]-1-propan-2-ylindole-3-carboxylic acid Chemical group C=1C=C(C=2C=C3N(C(C)C)C=C(C3=CC=2)C(O)=O)C=CC=1OCC1=C(C(C)C)ON=C1C1=C(Cl)C=CC=C1Cl KZSBGQYBMRPUGK-UHFFFAOYSA-N 0.000 claims 1
• UUYQPCIBFJNDPY-UHFFFAOYSA-N 6-[4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-1-benzothiophene-3-carboxylic acid Chemical compound C=1C=C(C=2C=C3SC=C(C3=CC=2)C(O)=O)C(C)=CC=1OCC1=C(C2CC2)ON=C1C1=C(Cl)C=CC=C1Cl UUYQPCIBFJNDPY-UHFFFAOYSA-N 0.000 claims 1
• ZOHJLACFQDZGGA-UHFFFAOYSA-N 6-[4-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-1-methylindole-3-carboxylic acid Chemical compound C=1C=C(C=2C=C3N(C)C=C(C3=CC=2)C(O)=O)C(C)=CC=1OCC1=C(C2CC2)ON=C1C1=CC=CC=C1OC(F)(F)F ZOHJLACFQDZGGA-UHFFFAOYSA-N 0.000 claims 1
• ONXZEWJFFDMQDE-UHFFFAOYSA-N 6-[4-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-2-methyl-1-benzofuran-3-carboxylic acid Chemical compound C=1C=C2C(C(O)=O)=C(C)OC2=CC=1C(C(=C1)C)=CC=C1OCC=1C(C=2C(=CC=CC=2)OC(F)(F)F)=NOC=1C1CC1 ONXZEWJFFDMQDE-UHFFFAOYSA-N 0.000 claims 1
• WRYFJPMYDZTZDM-UHFFFAOYSA-N 6-[4-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]phenyl]-1,2-benzothiazole-3-carboxylic acid Chemical group C=1C=C2C(C(=O)O)=NSC2=CC=1C(C=C1)=CC=C1OCC1=C(C2CC2)ON=C1C1=CC=CC=C1OC(F)(F)F WRYFJPMYDZTZDM-UHFFFAOYSA-N 0.000 claims 1
• JYOCNKHJCKGZQQ-UHFFFAOYSA-N 6-[4-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]phenyl]-1-methylindazole-3-carboxylic acid Chemical compound C1=C2N(C)N=C(C(O)=O)C2=CC=C1C(C=C1)=CC=C1OCC=1C(C=2C(=CC=CC=2)OC(F)(F)F)=NOC=1C1CC1 JYOCNKHJCKGZQQ-UHFFFAOYSA-N 0.000 claims 1
• XIRZPHUVMVDAIL-UHFFFAOYSA-N CC(C)c1onc(c1COc1ccc(c(C)c1)-c1cccc2oc(C)c(C(O)=O)c12)-c1c(Cl)cccc1Cl Chemical compound CC(C)c1onc(c1COc1ccc(c(C)c1)-c1cccc2oc(C)c(C(O)=O)c12)-c1c(Cl)cccc1Cl XIRZPHUVMVDAIL-UHFFFAOYSA-N 0.000 claims 1
• 230000003247 decreasing effect Effects 0.000 claims 1
• 125000004188 dichlorophenyl group Chemical group 0.000 claims 1
• 230000003028 elevating effect Effects 0.000 claims 1
• 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 13
• 201000010099 disease Diseases 0.000 abstract description 10
• 239000004033 plastic Substances 0.000 abstract description 2
• 229920003023 plastic Polymers 0.000 abstract description 2
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 280
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 202
• 239000000203 mixture Substances 0.000 description 156
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 128
• 239000000243 solution Substances 0.000 description 125
• 235000019439 ethyl acetate Nutrition 0.000 description 116
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 83
• 239000011541 reaction mixture Substances 0.000 description 59
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 58
• 238000006243 chemical reaction Methods 0.000 description 57
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 55
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 49
• 239000012044 organic layer Substances 0.000 description 46
• 239000007787 solid Substances 0.000 description 46
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
• 238000005160 1H NMR spectroscopy Methods 0.000 description 41
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
• 239000010410 layer Substances 0.000 description 35
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
• 238000003818 flash chromatography Methods 0.000 description 25
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 24
• 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 24
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
• 239000012267 brine Substances 0.000 description 23
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
• 238000010898 silica gel chromatography Methods 0.000 description 19
• 239000012043 crude product Substances 0.000 description 18
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
• 239000000706 filtrate Substances 0.000 description 17
• 239000011734 sodium Substances 0.000 description 17
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
• 239000002904 solvent Substances 0.000 description 16
• 239000000725 suspension Substances 0.000 description 15
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
• 235000019341 magnesium sulphate Nutrition 0.000 description 14
• 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 14
• 150000004702 methyl esters Chemical class 0.000 description 12
• 229910000027 potassium carbonate Inorganic materials 0.000 description 12
• 229910052938 sodium sulfate Inorganic materials 0.000 description 12
• 235000011152 sodium sulphate Nutrition 0.000 description 12
• 238000003756 stirring Methods 0.000 description 12
• 102100038495 Bile acid receptor Human genes 0.000 description 11
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 11
• 101000603876 Homo sapiens Bile acid receptor Proteins 0.000 description 11
• 235000011181 potassium carbonates Nutrition 0.000 description 11
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• 235000012000 cholesterol Nutrition 0.000 description 10
• 238000004587 chromatography analysis Methods 0.000 description 10
• 239000000047 product Substances 0.000 description 10
• 238000010992 reflux Methods 0.000 description 10
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• 229960000583 acetic acid Drugs 0.000 description 9
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
• 125000005843 halogen group Chemical group 0.000 description 9
• 239000003921 oil Substances 0.000 description 9
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 8
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 8
• 238000004440 column chromatography Methods 0.000 description 8
• 238000001914 filtration Methods 0.000 description 8
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 8
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
• 239000000741 silica gel Substances 0.000 description 8
• 229910002027 silica gel Inorganic materials 0.000 description 8
• 239000012312 sodium hydride Substances 0.000 description 8
• 229910000104 sodium hydride Inorganic materials 0.000 description 8
• 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 8
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 7
• 229910052799 carbon Inorganic materials 0.000 description 7
• KMAKOBLIOCQGJP-UHFFFAOYSA-N indole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CNC2=C1 KMAKOBLIOCQGJP-UHFFFAOYSA-N 0.000 description 7
• 239000005909 Kieselgur Substances 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 125000004432 carbon atom Chemical group C* 0.000 description 6
• 239000012065 filter cake Substances 0.000 description 6
• 150000002632 lipids Chemical class 0.000 description 6
• 239000012074 organic phase Substances 0.000 description 6
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• CFVZERGDGYZJHR-UHFFFAOYSA-N ethyl 2-bromo-4-propan-2-yl-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C=1SC(Br)=NC=1C(C)C CFVZERGDGYZJHR-UHFFFAOYSA-N 0.000 description 2
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• OERYMLHYCBBYLJ-UHFFFAOYSA-N methyl 2-(4-chloro-2-nitrophenyl)-3-hydroxybut-2-enoate Chemical compound COC(=O)C(=C(C)O)C1=CC=C(Cl)C=C1[N+]([O-])=O OERYMLHYCBBYLJ-UHFFFAOYSA-N 0.000 description 2
• SSWHBDSYYMBTKI-UHFFFAOYSA-N methyl 2-(5-bromo-1h-indol-3-yl)acetate Chemical compound C1=C(Br)C=C2C(CC(=O)OC)=CNC2=C1 SSWHBDSYYMBTKI-UHFFFAOYSA-N 0.000 description 2
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• IHXXYBKSTSUCGT-UHFFFAOYSA-N methyl 2-methyl-6-(trifluoromethylsulfonyloxy)-1-benzofuran-3-carboxylate Chemical compound FC(F)(F)S(=O)(=O)OC1=CC=C2C(C(=O)OC)=C(C)OC2=C1 IHXXYBKSTSUCGT-UHFFFAOYSA-N 0.000 description 2
• MIZNLOQJTYKTDH-UHFFFAOYSA-N methyl 2-oxo-2-(6-phenylmethoxy-1h-indol-3-yl)acetate Chemical compound C=1C=C2C(C(=O)C(=O)OC)=CNC2=CC=1OCC1=CC=CC=C1 MIZNLOQJTYKTDH-UHFFFAOYSA-N 0.000 description 2
• 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 2
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• WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-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
• 238000011156 evaluation Methods 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 230000007717 exclusion Effects 0.000 description 1
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• 230000002349 favourable effect Effects 0.000 description 1
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• 239000008103 glucose Substances 0.000 description 1
• 230000004153 glucose metabolism Effects 0.000 description 1
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• 125000004438 haloalkoxy group Chemical group 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
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• 229940125396 insulin Drugs 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 238000004020 luminiscence type Methods 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
• SJFNDMHZXCUXSA-UHFFFAOYSA-M methoxymethyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(COC)C1=CC=CC=C1 SJFNDMHZXCUXSA-UHFFFAOYSA-M 0.000 description 1
• ILKSQFJGMRVGCA-UHFFFAOYSA-N methyl 1-(2-methoxyethyl)indole-3-carboxylate Chemical compound C1=CC=C2N(CCOC)C=C(C(=O)OC)C2=C1 ILKSQFJGMRVGCA-UHFFFAOYSA-N 0.000 description 1
• RPSBSQWZEVPNKA-UHFFFAOYSA-N methyl 1-[2-(dimethylamino)ethyl]-6-(4-hydroxy-2-methylphenyl)indole-3-carboxylate Chemical compound C=1C=C2C(C(=O)OC)=CN(CCN(C)C)C2=CC=1C1=CC=C(O)C=C1C RPSBSQWZEVPNKA-UHFFFAOYSA-N 0.000 description 1
• ZELDTJAAMDIHDY-UHFFFAOYSA-N methyl 2-(4-hydroxy-2-methylphenyl)-4-methyl-1,3-thiazole-5-carboxylate Chemical compound CC1=C(C(=O)OC)SC(C=2C(=CC(O)=CC=2)C)=N1 ZELDTJAAMDIHDY-UHFFFAOYSA-N 0.000 description 1
• XFHXPFCCIGVOES-UHFFFAOYSA-N methyl 2-[5-(4-hydroxy-2-methylphenyl)-1h-indol-3-yl]acetate Chemical compound C1=C2C(CC(=O)OC)=CNC2=CC=C1C1=CC=C(O)C=C1C XFHXPFCCIGVOES-UHFFFAOYSA-N 0.000 description 1
• RKVCIABWEOYYOZ-UHFFFAOYSA-N methyl 2-bromo-4-methyl-1,3-thiazole-5-carboxylate Chemical compound COC(=O)C=1SC(Br)=NC=1C RKVCIABWEOYYOZ-UHFFFAOYSA-N 0.000 description 1
• RIJWDPRXCXJDPK-UHFFFAOYSA-N methyl 3-cyclopropyl-3-oxopropanoate Chemical compound COC(=O)CC(=O)C1CC1 RIJWDPRXCXJDPK-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
• LOYPKNMDUNGIOF-UHFFFAOYSA-N methyl 5-[4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1C(C(=C1)C)=CC=C1OCC1=C(C2CC2)ON=C1C1=C(Cl)C=CC=C1Cl LOYPKNMDUNGIOF-UHFFFAOYSA-N 0.000 description 1
• QZNZVRWWWOWDRV-UHFFFAOYSA-N methyl 5-bromo-1-benzothiophene-3-carboxylate Chemical compound C1=C(Br)C=C2C(C(=O)OC)=CSC2=C1 QZNZVRWWWOWDRV-UHFFFAOYSA-N 0.000 description 1
• DNHVXZDHGTWAQW-UHFFFAOYSA-N methyl 5-bromo-1h-indole-2-carboxylate Chemical compound BrC1=CC=C2NC(C(=O)OC)=CC2=C1 DNHVXZDHGTWAQW-UHFFFAOYSA-N 0.000 description 1
• IPBRHVDRTRBACF-UHFFFAOYSA-N methyl 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylate Chemical compound COC(=O)C1=C(C2CC2)ON=C1C1=C(Cl)C=CC=C1Cl IPBRHVDRTRBACF-UHFFFAOYSA-N 0.000 description 1
• DAFSGDFJRYGREQ-UHFFFAOYSA-N methyl 6-(4-hydroxy-2-methylphenyl)-1,2-benzothiazole-3-carboxylate Chemical compound C=1C=C2C(C(=O)OC)=NSC2=CC=1C1=CC=C(O)C=C1C DAFSGDFJRYGREQ-UHFFFAOYSA-N 0.000 description 1
• KGVJNBAZSXTWJW-UHFFFAOYSA-N methyl 6-(4-hydroxy-2-methylphenyl)-1-(2-methylsulfanylethyl)indole-3-carboxylate Chemical compound C=1C=C2C(C(=O)OC)=CN(CCSC)C2=CC=1C1=CC=C(O)C=C1C KGVJNBAZSXTWJW-UHFFFAOYSA-N 0.000 description 1
• INSNZBHWOMPOKH-UHFFFAOYSA-N methyl 6-(4-hydroxy-2-methylphenyl)-1-benzothiophene-3-carboxylate Chemical compound C=1C=C2C(C(=O)OC)=CSC2=CC=1C1=CC=C(O)C=C1C INSNZBHWOMPOKH-UHFFFAOYSA-N 0.000 description 1
• NRTWWGSSWOLVHM-UHFFFAOYSA-N methyl 6-(4-hydroxy-2-methylphenyl)-1-methylindole-3-carboxylate Chemical compound C=1C=C2C(C(=O)OC)=CN(C)C2=CC=1C1=CC=C(O)C=C1C NRTWWGSSWOLVHM-UHFFFAOYSA-N 0.000 description 1
• 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
• ASHFLMVXCNOCHI-UHFFFAOYSA-N methyl 6-(4-hydroxy-2-methylphenyl)-1h-indole-2-carboxylate Chemical compound C1=C2NC(C(=O)OC)=CC2=CC=C1C1=CC=C(O)C=C1C ASHFLMVXCNOCHI-UHFFFAOYSA-N 0.000 description 1
• WVMUVDHFXPLZAX-UHFFFAOYSA-N methyl 6-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-1h-indole-3-carboxylate Chemical compound C=1C=C2C(C(=O)OC)=CNC2=CC=1C(C(=C1)C)=CC=C1OCC(=C(ON=1)C(C)C)C=1C1=C(Cl)C=CC=C1Cl WVMUVDHFXPLZAX-UHFFFAOYSA-N 0.000 description 1
• GYGUKUIIBGFFEZ-UHFFFAOYSA-N methyl 6-[4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-2-methyl-1-benzofuran-3-carboxylate Chemical compound C=1C=C2C(C(=O)OC)=C(C)OC2=CC=1C(C(=C1)C)=CC=C1OCC1=C(C2CC2)ON=C1C1=C(Cl)C=CC=C1Cl GYGUKUIIBGFFEZ-UHFFFAOYSA-N 0.000 description 1
• POUNGHPAZUJZNT-UHFFFAOYSA-N methyl 6-bromo-1-(2-methylsulfanylethyl)indole-3-carboxylate Chemical compound BrC1=CC=C2C(C(=O)OC)=CN(CCSC)C2=C1 POUNGHPAZUJZNT-UHFFFAOYSA-N 0.000 description 1
• RVKHRBDHVYZAGL-UHFFFAOYSA-N methyl 6-bromo-1-[2-(dimethylamino)ethyl]indole-3-carboxylate Chemical compound BrC1=CC=C2C(C(=O)OC)=CN(CCN(C)C)C2=C1 RVKHRBDHVYZAGL-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
• JYORQPYGJQXAML-UHFFFAOYSA-N methyl 6-bromo-1-butylindole-3-carboxylate Chemical compound C1=C(Br)C=C2N(CCCC)C=C(C(=O)OC)C2=C1 JYORQPYGJQXAML-UHFFFAOYSA-N 0.000 description 1
• SJICLOHNXORMBV-UHFFFAOYSA-N methyl 6-bromo-1-methylindazole-3-carboxylate Chemical compound BrC1=CC=C2C(C(=O)OC)=NN(C)C2=C1 SJICLOHNXORMBV-UHFFFAOYSA-N 0.000 description 1
• HVSAEJIBGMVUJK-UHFFFAOYSA-N methyl 6-bromo-1-propan-2-ylindole-3-carboxylate Chemical compound BrC1=CC=C2C(C(=O)OC)=CN(C(C)C)C2=C1 HVSAEJIBGMVUJK-UHFFFAOYSA-N 0.000 description 1
• VXZQFDQHCLWBHX-UHFFFAOYSA-N methyl 6-chloro-1,2-dimethylindole-3-carboxylate Chemical compound ClC1=CC=C2C(C(=O)OC)=C(C)N(C)C2=C1 VXZQFDQHCLWBHX-UHFFFAOYSA-N 0.000 description 1
• RMEDXVIWDFLGES-UHFFFAOYSA-N methyl 6-chloropyridine-3-carboxylate Chemical compound COC(=O)C1=CC=C(Cl)N=C1 RMEDXVIWDFLGES-UHFFFAOYSA-N 0.000 description 1
• ODAVTXGNQNWWJZ-UHFFFAOYSA-N methyl 6-hydroxy-2-methyl-1-benzofuran-3-carboxylate Chemical compound OC1=CC=C2C(C(=O)OC)=C(C)OC2=C1 ODAVTXGNQNWWJZ-UHFFFAOYSA-N 0.000 description 1
• 125000006431 methyl cyclopropyl group Chemical group 0.000 description 1
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• 238000012986 modification Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
• YBSXDWIAUZOFFV-UHFFFAOYSA-N n-[(2,6-dichlorophenyl)methylidene]hydroxylamine Chemical compound ON=CC1=C(Cl)C=CC=C1Cl YBSXDWIAUZOFFV-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 229910052759 nickel Inorganic materials 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 235000020824 obesity Nutrition 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 238000003305 oral gavage Methods 0.000 description 1
• 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
• 239000012285 osmium tetroxide Substances 0.000 description 1
• JNGDFYLGDPAEBY-UHFFFAOYSA-N oxadiazole-4-thione Chemical compound S=C1CON=N1 JNGDFYLGDPAEBY-UHFFFAOYSA-N 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 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
• 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
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
• 229920000515 polycarbonate Polymers 0.000 description 1
• 239000004417 polycarbonate Substances 0.000 description 1
• 229920000728 polyester Polymers 0.000 description 1
• 235000011056 potassium acetate Nutrition 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 238000012545 processing Methods 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
• 239000012264 purified product Substances 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
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• 230000001105 regulatory effect Effects 0.000 description 1
• 239000012047 saturated solution Substances 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 230000008313 sensitization Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
• 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
• UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
• 229960002218 sodium chlorite Drugs 0.000 description 1
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
• 229910001379 sodium hypophosphite Inorganic materials 0.000 description 1
• 235000009518 sodium iodide Nutrition 0.000 description 1
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• 239000007858 starting material Substances 0.000 description 1
• 239000010959 steel Substances 0.000 description 1
• 125000000547 substituted alkyl group Chemical group 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
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• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
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• GKJLTLRSQRRBNI-UHFFFAOYSA-N tert-butyl 6-(4-hydroxy-2-methylphenyl)-1-benzofuran-3-carboxylate Chemical compound CC1=CC(O)=CC=C1C1=CC=C(C(=CO2)C(=O)OC(C)(C)C)C2=C1 GKJLTLRSQRRBNI-UHFFFAOYSA-N 0.000 description 1
• YEUIUUXECIWPTI-UHFFFAOYSA-N tert-butyl 6-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-1-benzofuran-2-carboxylate Chemical compound C=1C=C(C=2C=C3OC(=CC3=CC=2)C(=O)OC(C)(C)C)C(C)=CC=1OCC1=C(C(C)C)ON=C1C1=C(Cl)C=CC=C1Cl YEUIUUXECIWPTI-UHFFFAOYSA-N 0.000 description 1
• 238000011285 therapeutic regimen Methods 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
• ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 1
• 229930192474 thiophene Natural products 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
• 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
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