AU2007212126B2 - Compounds and methods for modulating FX-receptors - Google Patents

Info

Publication number

AU2007212126B2

AU2007212126B2 AU2007212126A AU2007212126A AU2007212126B2 AU 2007212126 B2 AU2007212126 B2 AU 2007212126B2 AU 2007212126 A AU2007212126 A AU 2007212126A AU 2007212126 A AU2007212126 A AU 2007212126A AU 2007212126 B2 AU2007212126 B2 AU 2007212126B2

Authority

AU

Australia

Prior art keywords

phenyl

methyl

carboxylic acid

isoxazol

isopropyl

Prior art date

2006-02-03

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Ceased

Links

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 230
• 238000000034 method Methods 0.000 title claims abstract description 27
• 208000032928 Dyslipidaemia Diseases 0.000 claims abstract description 18
• 208000017170 Lipid metabolism disease Diseases 0.000 claims abstract description 18
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 15
• 201000010099 disease Diseases 0.000 claims abstract description 12
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
• 238000002360 preparation method Methods 0.000 claims description 114
• -1 benzoisoxazolyl Chemical group 0.000 claims description 43
• 229910052739 hydrogen Inorganic materials 0.000 claims description 36
• 239000001257 hydrogen Substances 0.000 claims description 33
• 125000000217 alkyl group Chemical group 0.000 claims description 20
• 150000003839 salts Chemical class 0.000 claims description 19
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
• 150000002431 hydrogen Chemical class 0.000 claims description 16
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
• 125000005843 halogen group Chemical group 0.000 claims description 13
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 13
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 12
• 125000003944 tolyl group Chemical group 0.000 claims description 11
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
• 206010012601 diabetes mellitus Diseases 0.000 claims description 10
• 125000001153 fluoro group Chemical group F* 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
• 125000000335 thiazolyl group Chemical group 0.000 claims description 8
• 125000001544 thienyl group Chemical group 0.000 claims description 8
• 201000001320 Atherosclerosis Diseases 0.000 claims description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
• 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 4
• ZVTQYRVARPYRRE-UHFFFAOYSA-N oxadiazol-4-one Chemical compound O=C1CON=N1 ZVTQYRVARPYRRE-UHFFFAOYSA-N 0.000 claims description 4
• 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
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 230000008569 process Effects 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
• JNGDFYLGDPAEBY-UHFFFAOYSA-N oxadiazole-4-thione Chemical compound S=C1CON=N1 JNGDFYLGDPAEBY-UHFFFAOYSA-N 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
• 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 3
• QJFJBHYIIFGMSF-UHFFFAOYSA-N 6-[2-methyl-4-[[5-propan-2-yl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]phenyl]-1-benzothiophene-3-carboxylic acid Chemical compound C=1C=C(C=2C=C3SC=C(C3=CC=2)C(O)=O)C(C)=CC=1OCC1=C(C(C)C)ON=C1C1=CC=CC=C1OC(F)(F)F QJFJBHYIIFGMSF-UHFFFAOYSA-N 0.000 claims 2
• 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 compound 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 2
• 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 compound 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 2
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 1
• UDHVEBAZALTEPC-UHFFFAOYSA-N 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(O)=O)S1 UDHVEBAZALTEPC-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
• 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
• VXJUTMUZMNGPBO-UHFFFAOYSA-N 5-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-4-methylthiophene-2-carboxylic acid Chemical compound CC(C)C=1ON=C(C=2C(=CC=CC=2Cl)Cl)C=1COC(C=C1C)=CC=C1C=1SC(C(O)=O)=CC=1C VXJUTMUZMNGPBO-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
• CDHJFALRGJMKIE-UHFFFAOYSA-N 5-[4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]thiophene-2-carboxylic acid Chemical compound C=1C=C(C=2SC(=CC=2)C(O)=O)C(C)=CC=1OCC1=C(C2CC2)ON=C1C1=C(Cl)C=CC=C1Cl CDHJFALRGJMKIE-UHFFFAOYSA-N 0.000 claims 1
• DJIPMJOPIWKCLD-UHFFFAOYSA-N 6-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-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(C(C)C)ON=C1C1=C(Cl)C=CC=C1Cl DJIPMJOPIWKCLD-UHFFFAOYSA-N 0.000 claims 1
• CBZGTSZJINLFEQ-UHFFFAOYSA-N 6-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-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(C(C)C)ON=C1C1=C(Cl)C=CC=C1Cl CBZGTSZJINLFEQ-UHFFFAOYSA-N 0.000 claims 1
• OOOHZAYEJFWVSE-UHFFFAOYSA-N 6-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-2-methyl-1-benzofuran-3-carboxylic acid Chemical compound C=1C=C(C=2C=C3OC(C)=C(C(O)=O)C3=CC=2)C(C)=CC=1OCC1=C(C(C)C)ON=C1C1=C(Cl)C=CC=C1Cl OOOHZAYEJFWVSE-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
• PVQOIMYKUJFHSV-UHFFFAOYSA-N 6-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]-1,2-benzothiazole-3-carboxylic acid Chemical compound C=1C=C(C=2C=C3SN=C(C3=CC=2)C(O)=O)C=CC=1OCC1=C(C(C)C)ON=C1C1=C(Cl)C=CC=C1Cl PVQOIMYKUJFHSV-UHFFFAOYSA-N 0.000 claims 1
• 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 1
• XAAWGJUGXCHHTM-UHFFFAOYSA-N 6-[4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-1,2-benzoxazole-3-carboxylic acid Chemical compound C=1C=C(C=2C=C3ON=C(C3=CC=2)C(O)=O)C(C)=CC=1OCC=1C(C=2C(=CC=CC=2Cl)Cl)=NOC=1C1CC1 XAAWGJUGXCHHTM-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
• XIKIQAPAEXOOSR-UHFFFAOYSA-N 6-[4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]phenyl]-1,2-benzothiazole-3-carboxylic acid Chemical compound C=1C=C2C(C(=O)O)=NSC2=CC=1C(C=C1)=CC=C1OCC1=C(C2CC2)ON=C1C1=C(Cl)C=CC=C1Cl XIKIQAPAEXOOSR-UHFFFAOYSA-N 0.000 claims 1
• YDYNTEWMHLSXMZ-UHFFFAOYSA-N 6-[4-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-1-propan-2-ylindole-3-carboxylic acid Chemical compound C1=C2N(C(C)C)C=C(C(O)=O)C2=CC=C1C(C(=C1)C)=CC=C1OCC1=C(C2CC2)ON=C1C1=CC=CC=C1OC(F)(F)F YDYNTEWMHLSXMZ-UHFFFAOYSA-N 0.000 claims 1
• UICHUVJHVIHQHD-UHFFFAOYSA-N 6-[4-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-2-methyl-1-benzothiophene-3-carboxylic acid Chemical compound C=1C=C2C(C(O)=O)=C(C)SC2=CC=1C(C(=C1)C)=CC=C1OCC1=C(C2CC2)ON=C1C1=CC=CC=C1OC(F)(F)F UICHUVJHVIHQHD-UHFFFAOYSA-N 0.000 claims 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
• 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 293
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 173
• 239000000203 mixture Substances 0.000 description 152
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 143
• 239000000243 solution Substances 0.000 description 129
• 235000019439 ethyl acetate Nutrition 0.000 description 122
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 109
• 230000002829 reductive effect Effects 0.000 description 96
• 239000002253 acid Substances 0.000 description 85
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 83
• 239000011541 reaction mixture Substances 0.000 description 74
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 55
• 238000006243 chemical reaction Methods 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 49
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
• 239000007787 solid Substances 0.000 description 47
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
• 238000005481 NMR spectroscopy Methods 0.000 description 44
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 43
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
• 239000010410 layer Substances 0.000 description 36
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 34
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 32
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 29
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• 239000012267 brine Substances 0.000 description 26
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 26
• 238000003818 flash chromatography Methods 0.000 description 25
• 150000004702 methyl esters Chemical class 0.000 description 25
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 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 22
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• 239000012043 crude product Substances 0.000 description 20
• 238000010898 silica gel chromatography Methods 0.000 description 20
• 239000011734 sodium Substances 0.000 description 20
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
• 239000000706 filtrate 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
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
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• 125000004494 ethyl ester group Chemical group 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
• 238000010992 reflux Methods 0.000 description 14
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• 150000001732 carboxylic acid derivatives Chemical group 0.000 description 12
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• 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 10
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• 239000000047 product Substances 0.000 description 9
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
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• 238000001914 filtration Methods 0.000 description 8
• 150000002632 lipids Chemical class 0.000 description 8
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• 235000019341 magnesium sulphate Nutrition 0.000 description 8
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
• 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 8
• 238000005160 1H NMR spectroscopy Methods 0.000 description 7
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• BRWROFVPMUPMJQ-UHFFFAOYSA-N methyl 3-methylthiophene-2-carboxylate Chemical compound COC(=O)C=1SC=CC=1C BRWROFVPMUPMJQ-UHFFFAOYSA-N 0.000 description 1
• COVWTINOAVASMD-UHFFFAOYSA-N methyl 5-(2-chloro-4-hydroxyphenyl)-4-methylthiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC(C)=C1C1=CC=C(O)C=C1Cl COVWTINOAVASMD-UHFFFAOYSA-N 0.000 description 1
• KQHSDTRELVCLHW-UHFFFAOYSA-N methyl 5-(2-chloro-4-hydroxyphenyl)thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1C1=CC=C(O)C=C1Cl KQHSDTRELVCLHW-UHFFFAOYSA-N 0.000 description 1
• JXIFTJPLXDAQGY-UHFFFAOYSA-N methyl 5-(4-hydroxy-2-methylphenyl)-1h-indole-3-carboxylate Chemical compound C1=C2C(C(=O)OC)=CNC2=CC=C1C1=CC=C(O)C=C1C JXIFTJPLXDAQGY-UHFFFAOYSA-N 0.000 description 1
• 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 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
• 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
• QLWUHAQCKDHUNL-UHFFFAOYSA-N methyl 5-bromothiophene-2-carboxylate Chemical compound COC(=O)C1=CC=C(Br)S1 QLWUHAQCKDHUNL-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
• 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
• POIZYKIPHOHXDG-UHFFFAOYSA-N methyl 6-(4-hydroxy-2-methylphenyl)-2-methyl-1-propan-2-ylindole-3-carboxylate Chemical compound C=1C=C2C(C(=O)OC)=C(C)N(C(C)C)C2=CC=1C1=CC=C(O)C=C1C POIZYKIPHOHXDG-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
• 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
• RCDWEKOOOHATJC-UHFFFAOYSA-N methyl 6-bromo-1-methylindole-2-carboxylate Chemical compound C1=C(Br)C=C2N(C)C(C(=O)OC)=CC2=C1 RCDWEKOOOHATJC-UHFFFAOYSA-N 0.000 description 1
• RUBYSVHZXJRNLS-UHFFFAOYSA-N methyl 6-bromo-1-propan-2-ylindazole-3-carboxylate Chemical compound BrC1=CC=C2C(C(=O)OC)=NN(C(C)C)C2=C1 RUBYSVHZXJRNLS-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
• 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
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 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
• OQJBFFCUFALWQL-UHFFFAOYSA-N n-(piperidine-1-carbonylimino)piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)N=NC(=O)N1CCCCC1 OQJBFFCUFALWQL-UHFFFAOYSA-N 0.000 description 1
• 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
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• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
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• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 108020004017 nuclear receptors Proteins 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
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-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
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• 229920000515 polycarbonate Polymers 0.000 description 1
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• 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
• 238000012545 processing Methods 0.000 description 1
• KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
• HNDXKIMMSFCCFW-UHFFFAOYSA-N propane-2-sulphonic acid Chemical compound CC(C)S(O)(=O)=O HNDXKIMMSFCCFW-UHFFFAOYSA-N 0.000 description 1
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
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• 239000011369 resultant mixture Substances 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
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• XCFSBSSAXYTVSV-UHFFFAOYSA-N tert-butyl 6-phenylmethoxy-1-benzofuran-2-carboxylate Chemical compound C1=C2OC(C(=O)OC(C)(C)C)=CC2=CC=C1OCC1=CC=CC=C1 XCFSBSSAXYTVSV-UHFFFAOYSA-N 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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• 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
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• 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
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