ES2452031T3 - Compuestos y procedimientos para modular receptores FX - Google Patents

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Publication number

ES2452031T3

ES2452031T3 ES07763142.2T ES07763142T ES2452031T3 ES 2452031 T3 ES2452031 T3 ES 2452031T3 ES 07763142 T ES07763142 T ES 07763142T ES 2452031 T3 ES2452031 T3 ES 2452031T3

Authority

ES

Spain

Prior art keywords

phenyl

methyl

carboxylic acid

isoxazol

ylmethoxy

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.)

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 224
• 238000000034 method Methods 0.000 title description 18
• -1 benzoisoxazolyl Chemical group 0.000 claims abstract description 138
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 40
• 239000001257 hydrogen Substances 0.000 claims abstract description 38
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 30
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 27
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 18
• 150000003839 salts Chemical class 0.000 claims abstract description 18
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 10
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims abstract description 9
• 125000001041 indolyl group Chemical group 0.000 claims abstract description 9
• 125000000335 thiazolyl group Chemical group 0.000 claims abstract description 9
• 125000001544 thienyl group Chemical group 0.000 claims abstract description 9
• 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 6
• 125000004076 pyridyl group Chemical group 0.000 claims abstract description 6
• ZVTQYRVARPYRRE-UHFFFAOYSA-N oxadiazol-4-one Chemical compound O=C1CON=N1 ZVTQYRVARPYRRE-UHFFFAOYSA-N 0.000 claims abstract description 5
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims abstract description 4
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims abstract description 4
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims abstract description 4
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 3
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract description 3
• 239000002253 acid Substances 0.000 claims description 60
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
• 208000032928 Dyslipidaemia Diseases 0.000 claims description 12
• 208000017170 Lipid metabolism disease Diseases 0.000 claims description 12
• 239000000460 chlorine Substances 0.000 claims description 12
• 229910052801 chlorine Inorganic materials 0.000 claims description 12
• 125000000217 alkyl group Chemical group 0.000 claims description 11
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
• 125000005843 halogen group Chemical group 0.000 claims description 11
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 9
• 201000010099 disease Diseases 0.000 claims description 8
• 229910052731 fluorine Inorganic materials 0.000 claims description 8
• 239000011737 fluorine Substances 0.000 claims description 8
• 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 6
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
• 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 description 4
• 201000001320 Atherosclerosis Diseases 0.000 claims description 4
• 206010012601 diabetes mellitus Diseases 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 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 description 3
• 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 description 3
• 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 3
• 125000001153 fluoro group Chemical group F* 0.000 claims description 3
• 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 description 2
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
• 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 description 2
• 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 description 2
• HQWMJWTYHIPJEE-UHFFFAOYSA-N 6-[4-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-1,2-dimethylindole-3-carboxylic acid Chemical compound C1=C2N(C)C(C)=C(C(O)=O)C2=CC=C1C(C(=C1)C)=CC=C1OCC=1C(C=2C(=CC=CC=2)OC(F)(F)F)=NOC=1C1CC1 HQWMJWTYHIPJEE-UHFFFAOYSA-N 0.000 claims description 2
• JBTAABRROPVSJS-UHFFFAOYSA-N 6-[4-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-1-methylindole-2-carboxylic acid Chemical compound C=1C=C(C=2C=C3N(C)C(C(O)=O)=CC3=CC=2)C(C)=CC=1OCC1=C(C2CC2)ON=C1C1=CC=CC=C1OC(F)(F)F JBTAABRROPVSJS-UHFFFAOYSA-N 0.000 claims description 2
• 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 description 2
• 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 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
• 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
• 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
• 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
• 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 2
• 150000002431 hydrogen Chemical class 0.000 claims 2
• WBYOWKGKJGRIDX-UHFFFAOYSA-N 1-methyl-6-[2-methyl-4-[[5-propan-2-yl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]phenyl]indole-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=CC=CC=C1OC(F)(F)F WBYOWKGKJGRIDX-UHFFFAOYSA-N 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
• TUMQNQFLMXIJAC-UHFFFAOYSA-N 2-[4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-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(Cl)C=CC=C1Cl TUMQNQFLMXIJAC-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
• 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
• YABZYGXGQPZIAS-UHFFFAOYSA-N 6-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-1,2-dimethylindole-3-carboxylic acid Chemical compound C=1C=C(C=2C=C3N(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 YABZYGXGQPZIAS-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
• 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
• 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 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 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
• QOSBUFDWTQHHPA-UHFFFAOYSA-N 6-[4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-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=C(Cl)C=CC=C1Cl QOSBUFDWTQHHPA-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
• 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
• 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
• 238000002560 therapeutic procedure Methods 0.000 claims 1
• 125000001475 halogen functional group Chemical group 0.000 abstract 3
• JNGDFYLGDPAEBY-UHFFFAOYSA-N oxadiazole-4-thione Chemical compound S=C1CON=N1 JNGDFYLGDPAEBY-UHFFFAOYSA-N 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 289
• 239000000203 mixture Substances 0.000 description 157
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 145
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 139
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 134
• 239000000243 solution Substances 0.000 description 126
• 235000019439 ethyl acetate Nutrition 0.000 description 121
• 238000002360 preparation method Methods 0.000 description 118
• 230000002829 reductive effect Effects 0.000 description 98
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 87
• 229910001868 water Inorganic materials 0.000 description 77
• 239000011541 reaction mixture Substances 0.000 description 73
• 238000006243 chemical reaction Methods 0.000 description 58
• 239000012074 organic phase Substances 0.000 description 57
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 55
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 52
• 239000007787 solid Substances 0.000 description 49
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 47
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 47
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 46
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 39
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 37
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 35
• 238000005160 1H NMR spectroscopy Methods 0.000 description 33
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 32
• 150000004702 methyl esters Chemical class 0.000 description 31
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
• 229910052938 sodium sulfate Inorganic materials 0.000 description 30
• 235000011152 sodium sulphate Nutrition 0.000 description 30
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• FIRYVFXZPZNHBP-UHFFFAOYSA-N methyl 2-[1-methyl-6-(trifluoromethylsulfonyloxy)indol-3-yl]acetate Chemical compound FC(F)(F)S(=O)(=O)OC1=CC=C2C(CC(=O)OC)=CN(C)C2=C1 FIRYVFXZPZNHBP-UHFFFAOYSA-N 0.000 description 3
• BVLZMHRTGRUAKZ-UHFFFAOYSA-N methyl 2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran-3-carboxylate Chemical compound C=1C=C2C(C(=O)OC)=C(C)OC2=CC=1B1OC(C)(C)C(C)(C)O1 BVLZMHRTGRUAKZ-UHFFFAOYSA-N 0.000 description 3
• 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 3
• 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 3
• 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 3
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• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
• 239000012346 acetyl chloride Substances 0.000 description 2
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• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
• 229910000024 caesium carbonate Inorganic materials 0.000 description 2
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
• 208000029078 coronary artery disease Diseases 0.000 description 2
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• GGFKOVMZDAWYEX-UHFFFAOYSA-N dicyclohexyl-(1,3-dimethoxy-2-phenylcyclohexa-2,4-dien-1-yl)phosphane Chemical group C1CCCCC1P(C1CCCCC1)C1(OC)CC=CC(OC)=C1C1=CC=CC=C1 GGFKOVMZDAWYEX-UHFFFAOYSA-N 0.000 description 2
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
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• ODYHOIUFIVBVLS-UHFFFAOYSA-N ethyl 1-benzothiophene-5-carboxylate Chemical compound CCOC(=O)C1=CC=C2SC=CC2=C1 ODYHOIUFIVBVLS-UHFFFAOYSA-N 0.000 description 2
• DZYVXFNCEKBKJL-UHFFFAOYSA-N ethyl 1-cyclopropyl-5-hydroxy-2-methylindole-3-carboxylate Chemical compound C12=CC=C(O)C=C2C(C(=O)OCC)=C(C)N1C1CC1 DZYVXFNCEKBKJL-UHFFFAOYSA-N 0.000 description 2
• JOPRXFUJLQISBF-UHFFFAOYSA-N ethyl 2-(4-hydroxy-2-methylphenyl)-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(C=2C(=CC(O)=CC=2)C)=N1 JOPRXFUJLQISBF-UHFFFAOYSA-N 0.000 description 2
• WVTRTAJFTQLMBR-UHFFFAOYSA-N ethyl 2-(4-hydroxy-2-methylphenyl)-4-(trifluoromethyl)-1,3-thiazole-5-carboxylate Chemical compound FC(F)(F)C1=C(C(=O)OCC)SC(C=2C(=CC(O)=CC=2)C)=N1 WVTRTAJFTQLMBR-UHFFFAOYSA-N 0.000 description 2
• LQQOTNWQTCEPQJ-UHFFFAOYSA-N ethyl 2-(4-hydroxy-2-methylphenyl)-4-propyl-1,3-thiazole-5-carboxylate Chemical compound S1C(C(=O)OCC)=C(CCC)N=C1C1=CC=C(O)C=C1C LQQOTNWQTCEPQJ-UHFFFAOYSA-N 0.000 description 2
• YTALLKCUVAKJOW-UHFFFAOYSA-N ethyl 2-(4-hydroxyphenyl)-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)c1cnc(s1)-c1ccc(O)cc1 YTALLKCUVAKJOW-UHFFFAOYSA-N 0.000 description 2
• JSRLIKYMFUPJKF-UHFFFAOYSA-N ethyl 2-(4-methoxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate Chemical compound CC1=C(C(=O)OCC)SC(C=2C=CC(OC)=CC=2)=N1 JSRLIKYMFUPJKF-UHFFFAOYSA-N 0.000 description 2
• XGOWYXHVRJISDX-UHFFFAOYSA-N ethyl 2-(6-hydroxy-1-benzothiophen-3-yl)acetate Chemical compound OC1=CC=C2C(CC(=O)OCC)=CSC2=C1 XGOWYXHVRJISDX-UHFFFAOYSA-N 0.000 description 2
• SAYUBFVIKXSBTI-UHFFFAOYSA-N ethyl 2-amino-4-propan-2-yl-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C=1SC(N)=NC=1C(C)C SAYUBFVIKXSBTI-UHFFFAOYSA-N 0.000 description 2
• 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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• QNZMCEMVNKFVOA-UHFFFAOYSA-N ethyl 6-bromo-1-benzothiophene-2-carboxylate Chemical compound C1=C(Br)C=C2SC(C(=O)OCC)=CC2=C1 QNZMCEMVNKFVOA-UHFFFAOYSA-N 0.000 description 2
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• DEWFEMVAEWTLQM-UHFFFAOYSA-N ethyl 6-bromo-1-cyclopropyl-5-hydroxy-2-methylindole-3-carboxylate Chemical compound C12=CC(Br)=C(O)C=C2C(C(=O)OCC)=C(C)N1C1CC1 DEWFEMVAEWTLQM-UHFFFAOYSA-N 0.000 description 2
• DFAQILLIZCEVOU-UHFFFAOYSA-N ethyl 6-bromo-1-cyclopropyl-5-methoxy-2-methylindole-3-carboxylate Chemical compound C12=CC(Br)=C(OC)C=C2C(C(=O)OCC)=C(C)N1C1CC1 DFAQILLIZCEVOU-UHFFFAOYSA-N 0.000 description 2
• RXPGUNOYNYVCGK-UHFFFAOYSA-N ethyl 6-hydroxy-1-benzofuran-3-carboxylate Chemical compound OC1=CC=C2C(C(=O)OCC)=COC2=C1 RXPGUNOYNYVCGK-UHFFFAOYSA-N 0.000 description 2
• CSLCYFFJPLEVAX-UHFFFAOYSA-N ethyl 6-methoxy-1-benzofuran-3-carboxylate Chemical compound COC1=CC=C2C(C(=O)OCC)=COC2=C1 CSLCYFFJPLEVAX-UHFFFAOYSA-N 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
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• 229910052736 halogen Inorganic materials 0.000 description 2
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• 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
• OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 2
• 238000002844 melting Methods 0.000 description 2
• 230000008018 melting Effects 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
• MFMNLSWDVPSGBL-UHFFFAOYSA-N methyl 1-benzothiophene-7-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1SC=C2 MFMNLSWDVPSGBL-UHFFFAOYSA-N 0.000 description 2
• UDYWPDSXKAEITG-UHFFFAOYSA-N methyl 2-(1-methyl-6-phenylmethoxyindol-3-yl)-2-oxoacetate Chemical compound C=1C=C2C(C(=O)C(=O)OC)=CN(C)C2=CC=1OCC1=CC=CC=C1 UDYWPDSXKAEITG-UHFFFAOYSA-N 0.000 description 2
• KHXUTOLCCFWPDH-UHFFFAOYSA-N methyl 2-(4-bromo-2-nitrophenyl)acetate Chemical compound COC(=O)CC1=CC=C(Br)C=C1[N+]([O-])=O KHXUTOLCCFWPDH-UHFFFAOYSA-N 0.000 description 2
• 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 2
• LYNLCYUHINBULT-UHFFFAOYSA-N methyl 2-(4-methoxy-2-methylphenyl)-1-benzothiophene-7-carboxylate Chemical compound S1C=2C(C(=O)OC)=CC=CC=2C=C1C1=CC=C(OC)C=C1C LYNLCYUHINBULT-UHFFFAOYSA-N 0.000 description 2
• YQEATBQCQHPLHL-UHFFFAOYSA-N methyl 2-(6-hydroxy-1-methylindol-3-yl)acetate Chemical compound OC1=CC=C2C(CC(=O)OC)=CN(C)C2=C1 YQEATBQCQHPLHL-UHFFFAOYSA-N 0.000 description 2
• 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 2
• ALLIZWQVNLGXJL-UHFFFAOYSA-N methyl 2-[6-(4-hydroxy-2-methylphenyl)-1-benzothiophen-2-yl]acetate Chemical compound C1=C2SC(CC(=O)OC)=CC2=CC=C1C1=CC=C(O)C=C1C ALLIZWQVNLGXJL-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
• 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 2
• 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 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
• QLWUHAQCKDHUNL-UHFFFAOYSA-N methyl 5-bromothiophene-2-carboxylate Chemical compound COC(=O)C1=CC=C(Br)S1 QLWUHAQCKDHUNL-UHFFFAOYSA-N 0.000 description 2
• 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 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
• 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 2
• WKLAMMFIYQQZPD-UHFFFAOYSA-N methyl 6-(4-hydroxy-2-methylphenyl)-1h-indole-3-carboxylate Chemical compound C=1C=C2C(C(=O)OC)=CNC2=CC=1C1=CC=C(O)C=C1C WKLAMMFIYQQZPD-UHFFFAOYSA-N 0.000 description 2
• 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 2
• GHWMXIAQENLMIG-UHFFFAOYSA-N methyl 6-(4-hydroxy-2-methylphenyl)pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1C1=CC=C(O)C=C1C GHWMXIAQENLMIG-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 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 2
• 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 2
• 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 2
• 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 2
• 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 2
• FIPMZRPZSZXFGK-UHFFFAOYSA-N methyl 6-bromo-1h-indazole-3-carboxylate Chemical compound BrC1=CC=C2C(C(=O)OC)=NNC2=C1 FIPMZRPZSZXFGK-UHFFFAOYSA-N 0.000 description 2
• RPUAGJVFXJADEK-UHFFFAOYSA-N methyl 6-chloro-2-methyl-1h-indole-3-carboxylate Chemical compound ClC1=CC=C2C(C(=O)OC)=C(C)NC2=C1 RPUAGJVFXJADEK-UHFFFAOYSA-N 0.000 description 2
• OQJBFFCUFALWQL-UHFFFAOYSA-N n-(piperidine-1-carbonylimino)piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)N=NC(=O)N1CCCCC1 OQJBFFCUFALWQL-UHFFFAOYSA-N 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 230000001575 pathological effect Effects 0.000 description 2
• 230000007170 pathology Effects 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 239000002244 precipitate Substances 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 125000006239 protecting group Chemical group 0.000 description 2
• 230000004224 protection Effects 0.000 description 2
• 108090000623 proteins and genes Proteins 0.000 description 2
• 230000007115 recruitment Effects 0.000 description 2
• 238000002390 rotary evaporation Methods 0.000 description 2
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical group [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
• 239000012258 stirred mixture Substances 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 125000001424 substituent group Chemical group 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• 150000003456 sulfonamides Chemical class 0.000 description 2
• 239000011269 tar Substances 0.000 description 2
• 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 2
• JMEOCQVBRYEHJF-UHFFFAOYSA-N tert-butyl 6-hydroxy-1-benzofuran-2-carboxylate Chemical compound C1=C(O)C=C2OC(C(=O)OC(C)(C)C)=CC2=C1 JMEOCQVBRYEHJF-UHFFFAOYSA-N 0.000 description 2
• 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 2
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
• QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 2
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
• 229910052727 yttrium Inorganic materials 0.000 description 2
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
• LOCGPWGCRVKCFN-UHFFFAOYSA-N (2-chloro-4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C(Cl)=C1 LOCGPWGCRVKCFN-UHFFFAOYSA-N 0.000 description 1
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
• VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 1
• VJWFTDBWRPSNFS-UHFFFAOYSA-N (5-methoxycarbonylthiophen-2-yl)boronic acid Chemical compound COC(=O)C1=CC=C(B(O)O)S1 VJWFTDBWRPSNFS-UHFFFAOYSA-N 0.000 description 1
• 125000006527 (C1-C5) alkyl group Chemical group 0.000 description 1
• USVVENVKYJZFMW-ONEGZZNKSA-N (e)-carboxyiminocarbamic acid Chemical compound OC(=O)\N=N\C(O)=O USVVENVKYJZFMW-ONEGZZNKSA-N 0.000 description 1
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• ASCHFUIPHUEGQU-UHFFFAOYSA-N 1,2-dimethyl-6-[2-methyl-4-[[5-propan-2-yl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]phenyl]indole-3-carboxylic acid Chemical compound C=1C=C(C=2C=C3N(C)C(C)=C(C(O)=O)C3=CC=2)C(C)=CC=1OCC1=C(C(C)C)ON=C1C1=CC=CC=C1OC(F)(F)F ASCHFUIPHUEGQU-UHFFFAOYSA-N 0.000 description 1
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• ZKITXAAKDFPASL-UHFFFAOYSA-N 1-isothiocyanato-4-phenoxybenzene Chemical compound C1=CC(N=C=S)=CC=C1OC1=CC=CC=C1 ZKITXAAKDFPASL-UHFFFAOYSA-N 0.000 description 1
• KJYJJNGAPCAIHG-UHFFFAOYSA-N 1-propan-2-ylindole-3-carboxylic acid Chemical compound C1=CC=C2N(C(C)C)C=C(C(O)=O)C2=C1 KJYJJNGAPCAIHG-UHFFFAOYSA-N 0.000 description 1
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• PZAHFKDGJVYEOT-UHFFFAOYSA-N 2-(4-chloro-2-nitrophenyl)-3-hydroxybut-2-enoic acid Chemical compound ClC1=CC(=C(C=C1)C(C(=O)O)=C(C)O)[N+](=O)[O-] PZAHFKDGJVYEOT-UHFFFAOYSA-N 0.000 description 1
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• CPWICJMAGYIAQA-UHFFFAOYSA-N 2-[4-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-1-benzothiophene-5-carboxylic acid Chemical compound C=1C=C(C=2SC3=CC=C(C=C3C=2)C(O)=O)C(C)=CC=1OCC1=C(C2CC2)ON=C1C1=CC=CC=C1OC(F)(F)F CPWICJMAGYIAQA-UHFFFAOYSA-N 0.000 description 1
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• PARMUMMJPWVJHV-UHFFFAOYSA-N methyl 2-(4-hydroxy-2-methylphenyl)-4-propan-2-yl-1,3-thiazole-5-carboxylate Chemical compound COC(=O)c1sc(nc1C(C)C)-c1ccc(O)cc1C PARMUMMJPWVJHV-UHFFFAOYSA-N 0.000 description 1
• AJKSYJYYRICCNC-UHFFFAOYSA-N methyl 2-[4-[[5-cyclopropyl-3-[2-fluoro-6-(trifluoromethyl)phenyl]-1,2-oxazol-4-yl]methoxy]-2-methylphenyl]-4-methyl-1,3-thiazole-5-carboxylate Chemical compound CC1=C(C(=O)OC)SC(C=2C(=CC(OCC=3C(=NOC=3C3CC3)C=3C(=CC=CC=3F)C(F)(F)F)=CC=2)C)=N1 AJKSYJYYRICCNC-UHFFFAOYSA-N 0.000 description 1
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• RIJWDPRXCXJDPK-UHFFFAOYSA-N methyl 3-cyclopropyl-3-oxopropanoate Chemical compound COC(=O)CC(=O)C1CC1 RIJWDPRXCXJDPK-UHFFFAOYSA-N 0.000 description 1
• YNMFKBHALSXCCM-UHFFFAOYSA-N methyl 4-methyl-5-[2-methyl-4-[[5-propan-2-yl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]phenyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC(C)=C1C(C(=C1)C)=CC=C1OCC1=C(C(C)C)ON=C1C1=CC=CC=C1OC(F)(F)F YNMFKBHALSXCCM-UHFFFAOYSA-N 0.000 description 1
• WJWLMZQPKTUZAY-UHFFFAOYSA-N methyl 5-(4-hydroxy-2-methylphenyl)-1-benzothiophene-3-carboxylate Chemical compound C1=C2C(C(=O)OC)=CSC2=CC=C1C1=CC=C(O)C=C1C WJWLMZQPKTUZAY-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
• 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
• 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
• 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
• LJIIIOBYLKKAFM-UHFFFAOYSA-N methyl 6-(4-hydroxy-2-methylphenyl)-1-methylindazole-3-carboxylate Chemical compound C=1C=C2C(C(=O)OC)=NN(C)C2=CC=1C1=CC=C(O)C=C1C LJIIIOBYLKKAFM-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
• 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
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