CA2627090A1 - Benzimidazole derivatives for use as beta-3 receptor agonists - Google Patents

Info

Publication number

CA2627090A1

CA2627090A1 CA002627090A CA2627090A CA2627090A1 CA 2627090 A1 CA2627090 A1 CA 2627090A1 CA 002627090 A CA002627090 A CA 002627090A CA 2627090 A CA2627090 A CA 2627090A CA 2627090 A1 CA2627090 A1 CA 2627090A1

Authority

CA

Canada

Prior art keywords

phenyl

hydroxy

methyl

butyl

benzimidazole

Prior art date

2005-10-28

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title claims description 5
• 229940044601 receptor agonist Drugs 0.000 title description 3
• 239000000018 receptor agonist Substances 0.000 title description 3
• 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 97
• 239000000203 mixture Substances 0.000 claims abstract description 61
• 150000003839 salts Chemical class 0.000 claims abstract description 42
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 29
• 229940002612 prodrug Drugs 0.000 claims abstract description 13
• 239000000651 prodrug Substances 0.000 claims abstract description 13
• 150000004677 hydrates Chemical class 0.000 claims abstract description 11
• 239000012453 solvate Substances 0.000 claims abstract description 11
• 238000004519 manufacturing process Methods 0.000 claims abstract description 3
• -1 C1-3-alkyloxy Chemical group 0.000 claims description 74
• 125000000217 alkyl group Chemical group 0.000 claims description 41
• 229910052731 fluorine Inorganic materials 0.000 claims description 35
• 239000011737 fluorine Substances 0.000 claims description 35
• 239000000460 chlorine Substances 0.000 claims description 30
• 229910052801 chlorine Inorganic materials 0.000 claims description 30
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 27
• 239000013543 active substance Substances 0.000 claims description 27
• 125000004432 carbon atom Chemical group C* 0.000 claims description 27
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
• 125000001424 substituent group Chemical group 0.000 claims description 22
• FEOUBAYQXHYVTQ-UHFFFAOYSA-N 1-[3-[[2-[3-(benzenesulfonamido)phenyl]-2-hydroxyethyl]amino]-3-methylbutyl]benzimidazole-5-carboxylic acid Chemical compound C1=NC2=CC(C(O)=O)=CC=C2N1CCC(C)(C)NCC(O)C(C=1)=CC=CC=1NS(=O)(=O)C1=CC=CC=C1 FEOUBAYQXHYVTQ-UHFFFAOYSA-N 0.000 claims description 17
• OUDTVESPNOMJHI-UHFFFAOYSA-N ethyl 1-[3-[[2-[3-(benzenesulfonamido)phenyl]-2-hydroxyethyl]amino]-3-methylbutyl]benzimidazole-5-carboxylate Chemical compound C1=NC2=CC(C(=O)OCC)=CC=C2N1CCC(C)(C)NCC(O)C(C=1)=CC=CC=1NS(=O)(=O)C1=CC=CC=C1 OUDTVESPNOMJHI-UHFFFAOYSA-N 0.000 claims description 17
• 125000001246 bromo group Chemical group Br* 0.000 claims description 16
• LMWJQVTYANHCIM-UHFFFAOYSA-N n-[3-[2-[[4-(5-aminobenzimidazol-1-yl)-2-methylbutan-2-yl]amino]-1-hydroxyethyl]phenyl]benzenesulfonamide Chemical compound C1=NC2=CC(N)=CC=C2N1CCC(C)(C)NCC(O)C(C=1)=CC=CC=1NS(=O)(=O)C1=CC=CC=C1 LMWJQVTYANHCIM-UHFFFAOYSA-N 0.000 claims description 15
• 238000011282 treatment Methods 0.000 claims description 14
• 125000003277 amino group Chemical group 0.000 claims description 13
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
• 239000008194 pharmaceutical composition Substances 0.000 claims description 13
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 11
• 238000006243 chemical reaction Methods 0.000 claims description 11
• 238000000034 method Methods 0.000 claims description 10
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
• 239000003112 inhibitor Substances 0.000 claims description 9
• 125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 claims description 8
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
• 208000008589 Obesity Diseases 0.000 claims description 8
• 235000020824 obesity Nutrition 0.000 claims description 8
• 239000000969 carrier Substances 0.000 claims description 7
• FIHDRABZAAQKJG-UHFFFAOYSA-N n-[3-[2-[[4-(6-aminobenzimidazol-1-yl)-2-methylbutan-2-yl]amino]-1-hydroxyethyl]phenyl]benzenesulfonamide Chemical compound C1=NC2=CC=C(N)C=C2N1CCC(C)(C)NCC(O)C(C=1)=CC=CC=1NS(=O)(=O)C1=CC=CC=C1 FIHDRABZAAQKJG-UHFFFAOYSA-N 0.000 claims description 7
• 239000000126 substance Substances 0.000 claims description 7
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 7
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 6
• 230000000694 effects Effects 0.000 claims description 6
• 230000007717 exclusion Effects 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
• IWZSMSOBKJMUIB-VWLOTQADSA-N 1-[3-[[(2r)-2-[3-(benzenesulfonamido)phenyl]-2-hydroxyethyl]amino]-3-methylbutyl]-6-methoxybenzimidazole-5-carboxylic acid Chemical compound C=1C([C@@H](O)CNC(C)(C)CCN2C=3C=C(C(=CC=3N=C2)C(O)=O)OC)=CC=CC=1NS(=O)(=O)C1=CC=CC=C1 IWZSMSOBKJMUIB-VWLOTQADSA-N 0.000 claims description 5
• YSMUFEAIAAOFHE-MHZLTWQESA-N ethyl 3-[3-[[(2r)-2-[3-(benzenesulfonamido)phenyl]-2-hydroxyethyl]amino]-3-methylbutyl]benzimidazole-5-carboxylate Chemical compound C=1C([C@@H](O)CNC(C)(C)CCN2C=NC3=CC=C(C=C32)C(=O)OCC)=CC=CC=1NS(=O)(=O)C1=CC=CC=C1 YSMUFEAIAAOFHE-MHZLTWQESA-N 0.000 claims description 5
• 230000000638 stimulation Effects 0.000 claims description 5
• OIQFJYZHJGRDOB-QHCPKHFHSA-N 1-[3-[[(2r)-2-[3-(benzenesulfonamido)phenyl]-2-hydroxyethyl]amino]-3-methylbutyl]-4-chlorobenzimidazole-5-carboxylic acid Chemical compound C=1C([C@@H](O)CNC(C)(CCN2C3=CC=C(C(Cl)=C3N=C2)C(O)=O)C)=CC=CC=1NS(=O)(=O)C1=CC=CC=C1 OIQFJYZHJGRDOB-QHCPKHFHSA-N 0.000 claims description 4
• FEOUBAYQXHYVTQ-VWLOTQADSA-N 1-[3-[[(2r)-2-[3-(benzenesulfonamido)phenyl]-2-hydroxyethyl]amino]-3-methylbutyl]benzimidazole-5-carboxylic acid Chemical compound C=1C([C@@H](O)CNC(C)(CCN2C3=CC=C(C=C3N=C2)C(O)=O)C)=CC=CC=1NS(=O)(=O)C1=CC=CC=C1 FEOUBAYQXHYVTQ-VWLOTQADSA-N 0.000 claims description 4
• 230000001800 adrenalinergic effect Effects 0.000 claims description 4
• 230000006806 disease prevention Effects 0.000 claims description 4
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
• 125000001544 thienyl group Chemical group 0.000 claims description 4
• SILNNFMWIMZVEQ-JZRMKITLSA-N 1,3-dihydrobenzimidazol-2-one Chemical group C1=CC=C2N[11C](=O)NC2=C1 SILNNFMWIMZVEQ-JZRMKITLSA-N 0.000 claims description 3
• RTZVPEQPDBGUAV-HKBQPEDESA-N 2-morpholin-4-ylethyl 1-[3-[[(2r)-2-[3-(benzenesulfonamido)phenyl]-2-hydroxyethyl]amino]-3-methylbutyl]benzimidazole-5-carboxylate Chemical compound C([C@H](O)C=1C=C(NS(=O)(=O)C=2C=CC=CC=2)C=CC=1)NC(C)(C)CCN(C1=CC=2)C=NC1=CC=2C(=O)OCCN1CCOCC1 RTZVPEQPDBGUAV-HKBQPEDESA-N 0.000 claims description 3
• XLNVCXIQJAMZSB-QHCPKHFHSA-N 3-[3-[[(2r)-2-[3-(benzenesulfonamido)phenyl]-2-hydroxyethyl]amino]-3-methylbutyl]-4-chlorobenzimidazole-5-carboxylic acid Chemical compound C=1C([C@@H](O)CNC(C)(CCN2C3=C(Cl)C(C(O)=O)=CC=C3N=C2)C)=CC=CC=1NS(=O)(=O)C1=CC=CC=C1 XLNVCXIQJAMZSB-QHCPKHFHSA-N 0.000 claims description 3
• YZTYUSDPESXYFY-VWLOTQADSA-N 3-[3-[[(2r)-2-[3-(benzenesulfonamido)phenyl]-2-hydroxyethyl]amino]-3-methylbutyl]-6-chlorobenzimidazole-5-carboxylic acid Chemical compound C=1C([C@@H](O)CNC(C)(CCN2C3=CC(=C(Cl)C=C3N=C2)C(O)=O)C)=CC=CC=1NS(=O)(=O)C1=CC=CC=C1 YZTYUSDPESXYFY-VWLOTQADSA-N 0.000 claims description 3
• ISKUURKCGKMQGQ-VWLOTQADSA-N 3-[3-[[(2r)-2-[3-(benzenesulfonamido)phenyl]-2-hydroxyethyl]amino]-3-methylbutyl]benzimidazole-5-carboxylic acid Chemical compound C=1C([C@@H](O)CNC(C)(CCN2C3=CC(=CC=C3N=C2)C(O)=O)C)=CC=CC=1NS(=O)(=O)C1=CC=CC=C1 ISKUURKCGKMQGQ-VWLOTQADSA-N 0.000 claims description 3
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 3
• 101710204865 Tyrosine-protein phosphatase 1 Proteins 0.000 claims description 3
• 230000003178 anti-diabetic effect Effects 0.000 claims description 3
• 239000003524 antilipemic agent Substances 0.000 claims description 3
• 230000001906 cholesterol absorption Effects 0.000 claims description 3
• 230000002074 deregulated effect Effects 0.000 claims description 3
• YSMUFEAIAAOFHE-UHFFFAOYSA-N ethyl 3-[3-[[2-[3-(benzenesulfonamido)phenyl]-2-hydroxyethyl]amino]-3-methylbutyl]benzimidazole-5-carboxylate Chemical compound C12=CC(C(=O)OCC)=CC=C2N=CN1CCC(C)(C)NCC(O)C(C=1)=CC=CC=1NS(=O)(=O)C1=CC=CC=C1 YSMUFEAIAAOFHE-UHFFFAOYSA-N 0.000 claims description 3
• 230000009229 glucose formation Effects 0.000 claims description 3
• 210000004185 liver Anatomy 0.000 claims description 3
• 238000000926 separation method Methods 0.000 claims description 3
• 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
• KPUYFRHQLDMBNW-VWLOTQADSA-N 1-[3-[[(2r)-2-[3-(benzenesulfonamido)phenyl]-2-hydroxyethyl]amino]-3-methylbutyl]-6-hydroxybenzimidazole-5-carboxylic acid Chemical compound C=1C([C@@H](O)CNC(C)(CCN2C3=CC(O)=C(C(O)=O)C=C3N=C2)C)=CC=CC=1NS(=O)(=O)C1=CC=CC=C1 KPUYFRHQLDMBNW-VWLOTQADSA-N 0.000 claims description 2
• NYRVXGFFPAFXDM-UHFFFAOYSA-N 1-[3-[[2-[3-(benzenesulfonamido)phenyl]-2-hydroxyethyl]amino]-3-methylbutyl]-2-oxo-3h-benzimidazole-5-carboxylic acid Chemical compound C12=CC=C(C(O)=O)C=C2NC(=O)N1CCC(C)(C)NCC(O)C(C=1)=CC=CC=1NS(=O)(=O)C1=CC=CC=C1 NYRVXGFFPAFXDM-UHFFFAOYSA-N 0.000 claims description 2
• RTZVPEQPDBGUAV-UHFFFAOYSA-N 2-morpholin-4-ylethyl 1-[3-[[2-[3-(benzenesulfonamido)phenyl]-2-hydroxyethyl]amino]-3-methylbutyl]benzimidazole-5-carboxylate Chemical compound C=1C=CC(NS(=O)(=O)C=2C=CC=CC=2)=CC=1C(O)CNC(C)(C)CCN(C1=CC=2)C=NC1=CC=2C(=O)OCCN1CCOCC1 RTZVPEQPDBGUAV-UHFFFAOYSA-N 0.000 claims description 2
• ISKUURKCGKMQGQ-UHFFFAOYSA-N 3-[3-[[2-[3-(benzenesulfonamido)phenyl]-2-hydroxyethyl]amino]-3-methylbutyl]benzimidazole-5-carboxylic acid Chemical compound C1=NC2=CC=C(C(O)=O)C=C2N1CCC(C)(C)NCC(O)C(C=1)=CC=CC=1NS(=O)(=O)C1=CC=CC=C1 ISKUURKCGKMQGQ-UHFFFAOYSA-N 0.000 claims description 2
• 239000012320 chlorinating reagent Substances 0.000 claims description 2
• RNEXJMZCXHSHIZ-VWLOTQADSA-N n-[3-[(1r)-2-[[4-[5-(hydrazinecarbonyl)benzimidazol-1-yl]-2-methylbutan-2-yl]amino]-1-hydroxyethyl]phenyl]benzenesulfonamide Chemical compound C=1C([C@@H](O)CNC(C)(CCN2C3=CC=C(C=C3N=C2)C(=O)NN)C)=CC=CC=1NS(=O)(=O)C1=CC=CC=C1 RNEXJMZCXHSHIZ-VWLOTQADSA-N 0.000 claims description 2
• RNEXJMZCXHSHIZ-UHFFFAOYSA-N n-[3-[2-[[4-[5-(hydrazinecarbonyl)benzimidazol-1-yl]-2-methylbutan-2-yl]amino]-1-hydroxyethyl]phenyl]benzenesulfonamide Chemical compound C1=NC2=CC(C(=O)NN)=CC=C2N1CCC(C)(C)NCC(O)C(C=1)=CC=CC=1NS(=O)(=O)C1=CC=CC=C1 RNEXJMZCXHSHIZ-UHFFFAOYSA-N 0.000 claims description 2
• 125000006239 protecting group Chemical group 0.000 claims description 2
• 150000007524 organic acids Chemical class 0.000 abstract description 5
• 235000005985 organic acids Nutrition 0.000 abstract description 5
• 229940079593 drug Drugs 0.000 abstract description 4
• 239000003814 drug Substances 0.000 abstract description 4
• 150000007522 mineralic acids Chemical class 0.000 abstract description 4
• 229940125388 beta agonist Drugs 0.000 abstract description 2
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 171
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 171
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 167
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 111
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• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 73
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• 239000000741 silica gel Substances 0.000 description 72
• 229910002027 silica gel Inorganic materials 0.000 description 72
• 239000011541 reaction mixture Substances 0.000 description 69
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 59
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 58
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
• 239000000243 solution Substances 0.000 description 54
• 239000012071 phase Substances 0.000 description 36
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
• 229910021529 ammonia Inorganic materials 0.000 description 34
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
• 238000001704 evaporation Methods 0.000 description 30
• 230000008020 evaporation Effects 0.000 description 30
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 26
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 26
• 238000003818 flash chromatography Methods 0.000 description 25
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• 239000012074 organic phase Substances 0.000 description 24
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
• 239000003208 petroleum Substances 0.000 description 22
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
• 229920006395 saturated elastomer Polymers 0.000 description 21
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 18
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 18
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
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• 235000011152 sodium sulphate Nutrition 0.000 description 13
• 239000007787 solid Substances 0.000 description 13
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
• WKDNTKXTOZBKQV-UHFFFAOYSA-N n-[3-(2-ethoxy-2-hydroxyacetyl)phenyl]benzenesulfonamide Chemical compound CCOC(O)C(=O)C1=CC=CC(NS(=O)(=O)C=2C=CC=CC=2)=C1 WKDNTKXTOZBKQV-UHFFFAOYSA-N 0.000 description 12
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• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
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• 235000019341 magnesium sulphate Nutrition 0.000 description 9
• WHGHPURRSLRMIX-AWEZNQCLSA-N n-[3-[(2r)-oxiran-2-yl]phenyl]benzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)NC(C=1)=CC=CC=1[C@@H]1CO1 WHGHPURRSLRMIX-AWEZNQCLSA-N 0.000 description 9
• 239000011780 sodium chloride Substances 0.000 description 9
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• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
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• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
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• 235000019359 magnesium stearate Nutrition 0.000 description 7
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• 125000003342 alkenyl group Chemical group 0.000 description 6
• 125000000304 alkynyl group Chemical group 0.000 description 6
• 201000010099 disease Diseases 0.000 description 6
• 239000001257 hydrogen Substances 0.000 description 6
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• 229910052757 nitrogen Inorganic materials 0.000 description 6
• 208000020629 overactive bladder Diseases 0.000 description 6
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• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
• 229920002472 Starch Polymers 0.000 description 5
• 239000002585 base Substances 0.000 description 5
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
• 229910052794 bromium Inorganic materials 0.000 description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
• QYOUNCZBMWMEMY-UHFFFAOYSA-N ethyl 3-(3-amino-3-methylbutyl)benzimidazole-5-carboxylate Chemical compound CCOC(=O)C1=CC=C2N=CN(CCC(C)(C)N)C2=C1 QYOUNCZBMWMEMY-UHFFFAOYSA-N 0.000 description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
• 125000000623 heterocyclic group Chemical group 0.000 description 5
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
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• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
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• 239000008107 starch Substances 0.000 description 5
• 235000019698 starch Nutrition 0.000 description 5
• 239000000454 talc Substances 0.000 description 5
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