CA2551167C - Aminoalcohol derivatives - Google Patents
Aminoalcohol derivatives Download PDFInfo
- Publication number
- CA2551167C CA2551167C CA2551167A CA2551167A CA2551167C CA 2551167 C CA2551167 C CA 2551167C CA 2551167 A CA2551167 A CA 2551167A CA 2551167 A CA2551167 A CA 2551167A CA 2551167 C CA2551167 C CA 2551167C
- Authority
- CA
- Canada
- Prior art keywords
- ethyl
- amino
- hydroxy
- esi
- phenylethyl
- Prior art date
- 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.)
- Expired - Fee Related
Links
- 150000001414 amino alcohols Chemical class 0.000 title description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 147
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 106
- 150000003839 salts Chemical class 0.000 claims abstract description 54
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 53
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 41
- 239000001257 hydrogen Substances 0.000 claims abstract description 35
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 17
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 9
- 125000006239 protecting group Chemical group 0.000 claims abstract description 9
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 8
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 8
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 8
- 150000002367 halogens Chemical group 0.000 claims abstract description 8
- -1 benzyloxy, nitro, amino Chemical group 0.000 claims description 117
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 239000000048 adrenergic agonist Substances 0.000 claims description 6
- 229940126157 adrenergic receptor agonist Drugs 0.000 claims description 6
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000001589 carboacyl group Chemical group 0.000 claims description 5
- 206010020853 Hypertonic bladder Diseases 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 208000009722 Overactive Urinary Bladder Diseases 0.000 claims description 3
- 208000020629 overactive bladder Diseases 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 claims description 2
- XSRZJMIJNKWTJY-LJAQVGFWSA-N 2-(cyclohexylamino)-4-[4-[2-[[(2r)-2-hydroxy-2-phenylethyl]amino]ethyl]phenyl]-n-methylsulfonylbenzamide Chemical compound CS(=O)(=O)NC(=O)C1=CC=C(C=2C=CC(CCNC[C@H](O)C=3C=CC=CC=3)=CC=2)C=C1NC1CCCCC1 XSRZJMIJNKWTJY-LJAQVGFWSA-N 0.000 claims 1
- UPFBKTXPNTWJJX-LJAQVGFWSA-N 2-[2-cyclohexyloxy-4-[4-[2-[[(2r)-2-hydroxy-2-phenylethyl]amino]ethyl]phenyl]phenyl]-n-methylsulfonylacetamide Chemical compound CS(=O)(=O)NC(=O)CC1=CC=C(C=2C=CC(CCNC[C@H](O)C=3C=CC=CC=3)=CC=2)C=C1OC1CCCCC1 UPFBKTXPNTWJJX-LJAQVGFWSA-N 0.000 claims 1
- JTSVLQHPARDDKT-NDEPHWFRSA-N 2-[2-cyclohexyloxy-4-[4-[2-[[(2r)-2-hydroxy-2-pyridin-3-ylethyl]amino]ethyl]phenyl]phenyl]-n-methylsulfonylacetamide Chemical compound CS(=O)(=O)NC(=O)CC1=CC=C(C=2C=CC(CCNC[C@H](O)C=3C=NC=CC=3)=CC=2)C=C1OC1CCCCC1 JTSVLQHPARDDKT-NDEPHWFRSA-N 0.000 claims 1
- WWFRXUDMACTFBI-NDEPHWFRSA-N 2-cyclohexyloxy-4-[4-[2-[[(2r)-2-hydroxy-2-phenylethyl]amino]ethyl]phenyl]-n-methylsulfonylbenzamide Chemical compound CS(=O)(=O)NC(=O)C1=CC=C(C=2C=CC(CCNC[C@H](O)C=3C=CC=CC=3)=CC=2)C=C1OC1CCCCC1 WWFRXUDMACTFBI-NDEPHWFRSA-N 0.000 claims 1
- YLQMAAMFQNYJDU-MHZLTWQESA-N 2-cyclohexyloxy-4-[4-[2-[[(2r)-2-hydroxy-2-pyridin-3-ylethyl]amino]ethyl]phenyl]-n-methylsulfonylbenzamide Chemical compound CS(=O)(=O)NC(=O)C1=CC=C(C=2C=CC(CCNC[C@H](O)C=3C=NC=CC=3)=CC=2)C=C1OC1CCCCC1 YLQMAAMFQNYJDU-MHZLTWQESA-N 0.000 claims 1
- SITWWMFSARAANL-KMRXNPHXSA-N 4-[4-[2-[[(1r,2s)-1-hydroxy-1-phenylpropan-2-yl]amino]ethyl]phenyl]-2-(2-methylpropyl)-n-methylsulfonylbenzamide Chemical compound C1=C(C(=O)NS(C)(=O)=O)C(CC(C)C)=CC(C=2C=CC(CCN[C@@H](C)[C@H](O)C=3C=CC=CC=3)=CC=2)=C1 SITWWMFSARAANL-KMRXNPHXSA-N 0.000 claims 1
- FKGYWDPSUXSSQK-MHZLTWQESA-N 4-[4-[2-[[(2r)-2-hydroxy-2-phenylethyl]amino]ethyl]phenyl]-2-(2-methylpropyl)-n-methylsulfonylbenzamide Chemical compound C1=C(C(=O)NS(C)(=O)=O)C(CC(C)C)=CC(C=2C=CC(CCNC[C@H](O)C=3C=CC=CC=3)=CC=2)=C1 FKGYWDPSUXSSQK-MHZLTWQESA-N 0.000 claims 1
- IXBYTCUCLIPCPM-NDEPHWFRSA-N 4-[4-[2-[[(2r)-2-hydroxy-2-phenylethyl]amino]ethyl]phenyl]-2-(3-methylbutyl)-n-methylsulfonylbenzamide Chemical compound C1=C(C(=O)NS(C)(=O)=O)C(CCC(C)C)=CC(C=2C=CC(CCNC[C@H](O)C=3C=CC=CC=3)=CC=2)=C1 IXBYTCUCLIPCPM-NDEPHWFRSA-N 0.000 claims 1
- FEQQLEGJQNYEQY-SANMLTNESA-N 4-[4-[2-[[(2r)-2-hydroxy-2-phenylethyl]amino]ethyl]phenyl]-n-methylsulfonyl-2-(propan-2-ylamino)benzamide Chemical compound C1=C(C(=O)NS(C)(=O)=O)C(NC(C)C)=CC(C=2C=CC(CCNC[C@H](O)C=3C=CC=CC=3)=CC=2)=C1 FEQQLEGJQNYEQY-SANMLTNESA-N 0.000 claims 1
- HXFKZSVPCHUKBX-VWLOTQADSA-N 4-[4-[2-[[(2r)-2-hydroxy-2-phenylethyl]amino]ethyl]phenyl]-n-methylsulfonyl-2-propan-2-ylsulfanylbenzamide Chemical compound C1=C(C(=O)NS(C)(=O)=O)C(SC(C)C)=CC(C=2C=CC(CCNC[C@H](O)C=3C=CC=CC=3)=CC=2)=C1 HXFKZSVPCHUKBX-VWLOTQADSA-N 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- HGOKKKSGWRCIHE-NDEPHWFRSA-N n-[2-cyclohexyloxy-4-[4-[2-[[(2r)-2-hydroxy-2-phenylethyl]amino]ethyl]phenyl]phenyl]sulfonylacetamide Chemical compound CC(=O)NS(=O)(=O)C1=CC=C(C=2C=CC(CCNC[C@H](O)C=3C=CC=CC=3)=CC=2)C=C1OC1CCCCC1 HGOKKKSGWRCIHE-NDEPHWFRSA-N 0.000 claims 1
- IWTORKZSDKQKNR-LJAQVGFWSA-N n-[2-cyclohexyloxy-4-[4-[2-[[(2r)-2-hydroxy-2-phenylethyl]amino]ethyl]phenyl]phenyl]sulfonylbutanamide Chemical compound CCCC(=O)NS(=O)(=O)C1=CC=C(C=2C=CC(CCNC[C@H](O)C=3C=CC=CC=3)=CC=2)C=C1OC1CCCCC1 IWTORKZSDKQKNR-LJAQVGFWSA-N 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 5
- 230000001225 therapeutic effect Effects 0.000 abstract description 4
- 206010046543 Urinary incontinence Diseases 0.000 abstract description 2
- 230000000069 prophylactic effect Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 486
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 442
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 284
- 239000000203 mixture Substances 0.000 description 274
- 239000000243 solution Substances 0.000 description 191
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 168
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 161
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 145
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 144
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 131
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 113
- 238000002360 preparation method Methods 0.000 description 103
- 239000012267 brine Substances 0.000 description 97
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 96
- 230000002829 reductive effect Effects 0.000 description 94
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 93
- 239000012044 organic layer Substances 0.000 description 83
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 80
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 78
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 76
- 235000019341 magnesium sulphate Nutrition 0.000 description 75
- 239000011734 sodium Substances 0.000 description 70
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 68
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 61
- 239000000741 silica gel Substances 0.000 description 61
- 229910002027 silica gel Inorganic materials 0.000 description 61
- 238000004440 column chromatography Methods 0.000 description 54
- 239000007787 solid Substances 0.000 description 54
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 46
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 44
- 238000001914 filtration Methods 0.000 description 43
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 40
- 239000000047 product Substances 0.000 description 38
- 238000001704 evaporation Methods 0.000 description 37
- 230000008020 evaporation Effects 0.000 description 37
- 239000011541 reaction mixture Substances 0.000 description 35
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 31
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 29
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 29
- 239000007864 aqueous solution Substances 0.000 description 28
- 238000001816 cooling Methods 0.000 description 27
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 26
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 25
- 229910052757 nitrogen Inorganic materials 0.000 description 23
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- 239000000725 suspension Substances 0.000 description 19
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
- 229910052938 sodium sulfate Inorganic materials 0.000 description 18
- 235000011152 sodium sulphate Nutrition 0.000 description 18
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 18
- 239000003480 eluent Substances 0.000 description 17
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 17
- 238000000034 method Methods 0.000 description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 16
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
- PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 239000010410 layer Substances 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000002244 precipitate Substances 0.000 description 14
- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 13
- 229910000029 sodium carbonate Inorganic materials 0.000 description 13
- 101150041968 CDC13 gene Proteins 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 12
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 12
- 230000002265 prevention Effects 0.000 description 12
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 239000006260 foam Substances 0.000 description 10
- 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 10
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 9
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 9
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 9
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 description 9
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 8
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 235000011181 potassium carbonates Nutrition 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 8
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 7
- 230000036724 intravesical pressure Effects 0.000 description 7
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- 125000004430 oxygen atom Chemical group O* 0.000 description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 6
- 235000011056 potassium acetate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- ZQQSRVPOAHYHEL-UHFFFAOYSA-N 4-bromo-2-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C=C1F ZQQSRVPOAHYHEL-UHFFFAOYSA-N 0.000 description 5
- 239000005711 Benzoic acid Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
- 235000010233 benzoic acid Nutrition 0.000 description 5
- 229960004365 benzoic acid Drugs 0.000 description 5
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
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- 230000005764 inhibitory process Effects 0.000 description 2
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- ZSGLAKVEUUXMBG-SFCXHYMASA-N methyl 2-amino-4-[4-[2-[benzyl-[(2r)-2-(oxan-2-yloxy)-2-phenylethyl]amino]ethyl]phenyl]benzoate Chemical compound C1=C(N)C(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(CC=1C=CC=CC=1)C[C@@H](C=1C=CC=CC=1)OC1OCCCC1 ZSGLAKVEUUXMBG-SFCXHYMASA-N 0.000 description 2
- CIRLWCKMKNJVHC-YTTGMZPUSA-N methyl 2-cyclohexyloxy-4-[4-[3-[[(2r)-2-hydroxy-2-phenylethyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]propyl]phenyl]benzoate Chemical compound COC(=O)C1=CC=C(C=2C=CC(CCCN(C[C@H](O)C=3C=CC=CC=3)C(=O)OC(C)(C)C)=CC=2)C=C1OC1CCCCC1 CIRLWCKMKNJVHC-YTTGMZPUSA-N 0.000 description 2
- ZRBHEUPJVPCIHW-MHZLTWQESA-N methyl 2-ethylsulfanyl-4-[4-[2-[[(2r)-2-hydroxy-2-phenylethyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]phenyl]benzoate Chemical compound C1=C(C(=O)OC)C(SCC)=CC(C=2C=CC(CCN(C[C@H](O)C=3C=CC=CC=3)C(=O)OC(C)(C)C)=CC=2)=C1 ZRBHEUPJVPCIHW-MHZLTWQESA-N 0.000 description 2
- KUGACAIEYZIXPK-FSRLHOSWSA-N methyl 2-hydroxy-4-[4-[2-[(2-methylpropan-2-yl)oxycarbonyl-[(2r)-2-(oxan-2-yloxy)-2-phenylethyl]amino]ethyl]phenyl]benzoate Chemical compound C1=C(O)C(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(C(=O)OC(C)(C)C)C[C@@H](C=1C=CC=CC=1)OC1OCCCC1 KUGACAIEYZIXPK-FSRLHOSWSA-N 0.000 description 2
- PCVWZTOPCXSREW-SANMLTNESA-N methyl 3-amino-4-[4-[2-[[(2r)-2-hydroxy-2-phenylethyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]phenyl]benzoate Chemical compound NC1=CC(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(C(=O)OC(C)(C)C)C[C@H](O)C1=CC=CC=C1 PCVWZTOPCXSREW-SANMLTNESA-N 0.000 description 2
- RCRFCDIKOVOWOQ-UHFFFAOYSA-N methyl 4-[4-(2-bromoethoxy)phenyl]-2-propan-2-ylsulfanylbenzoate Chemical compound C1=C(SC(C)C)C(C(=O)OC)=CC=C1C1=CC=C(OCCBr)C=C1 RCRFCDIKOVOWOQ-UHFFFAOYSA-N 0.000 description 2
- OYWCSKZUBNZORU-UHFFFAOYSA-N methyl 4-[4-[2-(benzylamino)ethyl]phenyl]-2-(propan-2-ylamino)benzoate Chemical compound C1=C(NC(C)C)C(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCNCC1=CC=CC=C1 OYWCSKZUBNZORU-UHFFFAOYSA-N 0.000 description 2
- HXINFUSZVDGRRI-PPHZAIPVSA-N methyl 4-[4-[2-[[(1r,2s)-1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl]amino]ethoxy]phenyl]-2-propan-2-ylsulfanylbenzoate Chemical compound C1=C(SC(C)C)C(C(=O)OC)=CC=C1C(C=C1)=CC=C1OCCN[C@@H](C)[C@H](O)C1=CC=C(O)C=C1 HXINFUSZVDGRRI-PPHZAIPVSA-N 0.000 description 2
- KDRSERPUOSMQQU-UMSFTDKQSA-N methyl 4-[4-[2-[[(2r)-2-(6-acetamidopyridin-3-yl)-2-[tert-butyl(dimethyl)silyl]oxyethyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]phenyl]-2-propan-2-yloxybenzoate Chemical compound C1=C(OC(C)C)C(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(C(=O)OC(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)C1=CC=C(NC(C)=O)N=C1 KDRSERPUOSMQQU-UMSFTDKQSA-N 0.000 description 2
- ZHICBWUCPHAXEG-NDEPHWFRSA-N methyl 4-[4-[2-[[(2r)-2-hydroxy-2-phenylethyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]phenyl]-2-propan-2-yloxybenzoate Chemical compound C1=C(OC(C)C)C(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(C(=O)OC(C)(C)C)C[C@H](O)C1=CC=CC=C1 ZHICBWUCPHAXEG-NDEPHWFRSA-N 0.000 description 2
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- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
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- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
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- 239000011777 magnesium Substances 0.000 description 1
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- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
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- 208000024714 major depressive disease Diseases 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 201000003995 melancholia Diseases 0.000 description 1
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- IYZUZJZZWIWGGX-NDEPHWFRSA-N methyl 2-acetamido-4-[4-[2-[[(2r)-2-hydroxy-2-phenylethyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]phenyl]benzoate Chemical compound C1=C(NC(C)=O)C(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(C(=O)OC(C)(C)C)C[C@H](O)C1=CC=CC=C1 IYZUZJZZWIWGGX-NDEPHWFRSA-N 0.000 description 1
- GARLALCTMRSWTH-YTTGMZPUSA-N methyl 2-acetamido-4-[4-[2-[benzyl-[(2r)-2-hydroxy-2-phenylethyl]amino]ethyl]phenyl]benzoate Chemical compound C1=C(NC(C)=O)C(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(CC=1C=CC=CC=1)C[C@H](O)C1=CC=CC=C1 GARLALCTMRSWTH-YTTGMZPUSA-N 0.000 description 1
- IHSNQFLLICTCGG-SANMLTNESA-N methyl 2-amino-4-[4-[2-[[(2R)-2-hydroxy-2-phenylethyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]phenyl]benzoate Chemical compound C1=C(N)C(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(C(=O)OC(C)(C)C)C[C@H](O)C1=CC=CC=C1 IHSNQFLLICTCGG-SANMLTNESA-N 0.000 description 1
- LXDIVDJHNBHNQU-NWDJCJOJSA-N methyl 2-cyclohexyloxy-4-[4-[2-[(2-methylpropan-2-yl)oxycarbonyl-[(2r)-2-(oxan-2-yloxy)-2-phenylethyl]amino]ethyl]phenyl]benzoate Chemical compound COC(=O)C1=CC=C(C=2C=CC(CCN(C[C@H](OC3OCCCC3)C=3C=CC=CC=3)C(=O)OC(C)(C)C)=CC=2)C=C1OC1CCCCC1 LXDIVDJHNBHNQU-NWDJCJOJSA-N 0.000 description 1
- CRLUFCYUQYSETR-UHFFFAOYSA-N methyl 2-propan-2-ylsulfanyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate Chemical compound C1=C(SC(C)C)C(C(=O)OC)=CC=C1B1OC(C)(C)C(C)(C)O1 CRLUFCYUQYSETR-UHFFFAOYSA-N 0.000 description 1
- OJHMZWHKSAGJSZ-NDEPHWFRSA-N methyl 3-(dimethylamino)-4-[4-[2-[[(2r)-2-hydroxy-2-phenylethyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]phenyl]benzoate Chemical compound CN(C)C1=CC(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(C(=O)OC(C)(C)C)C[C@H](O)C1=CC=CC=C1 OJHMZWHKSAGJSZ-NDEPHWFRSA-N 0.000 description 1
- RPKQXHNACTWKQY-UHFFFAOYSA-N methyl 3-nitro-4-(trifluoromethylsulfonyloxy)benzoate Chemical compound COC(=O)C1=CC=C(OS(=O)(=O)C(F)(F)F)C([N+]([O-])=O)=C1 RPKQXHNACTWKQY-UHFFFAOYSA-N 0.000 description 1
- YFFHEBWISYUWLD-UHFFFAOYSA-N methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-thiophen-2-ylbenzoate Chemical compound COC(=O)C1=CC=C(B2OC(C)(C)C(C)(C)O2)C=C1C1=CC=CS1 YFFHEBWISYUWLD-UHFFFAOYSA-N 0.000 description 1
- FIAFCQOCWXUULV-UHFFFAOYSA-N methyl 4-[4-(2-amino-2-methylpropyl)phenyl]-2-(2-methylpropyl)benzoate Chemical compound C1=C(CC(C)C)C(C(=O)OC)=CC=C1C1=CC=C(CC(C)(C)N)C=C1 FIAFCQOCWXUULV-UHFFFAOYSA-N 0.000 description 1
- GXTYVWFXPKBJRB-UHFFFAOYSA-N methyl 4-[4-(2-hydroxyethoxy)phenyl]-2-propan-2-ylsulfanylbenzoate Chemical compound C1=C(SC(C)C)C(C(=O)OC)=CC=C1C1=CC=C(OCCO)C=C1 GXTYVWFXPKBJRB-UHFFFAOYSA-N 0.000 description 1
- OMTCPABWAXNQBJ-DLLPINGYSA-N methyl 4-[4-[2-[[(1r,2s)-1-hydroxy-1-phenylpropan-2-yl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]phenyl]-2-(2-methylpropyl)benzoate Chemical compound C1=C(CC(C)C)C(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(C(=O)OC(C)(C)C)[C@@H](C)[C@H](O)C1=CC=CC=C1 OMTCPABWAXNQBJ-DLLPINGYSA-N 0.000 description 1
- YDRUYKWJJGESOP-JHOBJCJYSA-N methyl 4-[4-[2-[[(1r,2s)-1-hydroxy-1-phenylpropan-2-yl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]phenyl]-2-propan-2-ylsulfanylbenzoate Chemical compound C1=C(SC(C)C)C(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(C(=O)OC(C)(C)C)[C@@H](C)[C@H](O)C1=CC=CC=C1 YDRUYKWJJGESOP-JHOBJCJYSA-N 0.000 description 1
- MZTJOSQMGQAVQE-NDEPHWFRSA-N methyl 4-[4-[2-[[(2r)-2-(3-aminophenyl)-2-hydroxyethyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]phenyl]-2-propan-2-yloxybenzoate Chemical compound C1=C(OC(C)C)C(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(C(=O)OC(C)(C)C)C[C@H](O)C1=CC=CC(N)=C1 MZTJOSQMGQAVQE-NDEPHWFRSA-N 0.000 description 1
- BNLXBDOLKOEENU-LHEWISCISA-N methyl 4-[4-[2-[[(2r)-2-(6-acetamidopyridin-3-yl)-2-[tert-butyl(dimethyl)silyl]oxyethyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]phenyl]-2-cycloheptyloxybenzoate Chemical compound COC(=O)C1=CC=C(C=2C=CC(CCN(C[C@H](O[Si](C)(C)C(C)(C)C)C=3C=NC(NC(C)=O)=CC=3)C(=O)OC(C)(C)C)=CC=2)C=C1OC1CCCCCC1 BNLXBDOLKOEENU-LHEWISCISA-N 0.000 description 1
- TVSRXDYLNPEXAU-DHUJRADRSA-N methyl 4-[4-[2-[[(2r)-2-hydroxy-2-(3-phenylmethoxyphenyl)ethyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]phenyl]-2-propan-2-yloxybenzoate Chemical compound C1=C(OC(C)C)C(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(C(=O)OC(C)(C)C)C[C@H](O)C1=CC=CC(OCC=2C=CC=CC=2)=C1 TVSRXDYLNPEXAU-DHUJRADRSA-N 0.000 description 1
- VSIRNRHUULOSMV-LJAQVGFWSA-N methyl 4-[4-[2-[[(2r)-2-hydroxy-2-phenylethyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]phenyl]-2-(propan-2-ylamino)benzoate Chemical compound C1=C(NC(C)C)C(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(C(=O)OC(C)(C)C)C[C@H](O)C1=CC=CC=C1 VSIRNRHUULOSMV-LJAQVGFWSA-N 0.000 description 1
- RDLMBWALUMEMJS-NDEPHWFRSA-N methyl 4-[4-[2-[[(2r)-2-hydroxy-2-phenylethyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]phenyl]-2-propan-2-ylsulfanylbenzoate Chemical compound C1=C(SC(C)C)C(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(C(=O)OC(C)(C)C)C[C@H](O)C1=CC=CC=C1 RDLMBWALUMEMJS-NDEPHWFRSA-N 0.000 description 1
- DLMAFWRGCFHXPU-LJAQVGFWSA-N methyl 4-[4-[2-[[(2r)-2-hydroxy-2-pyridin-3-ylethyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]phenyl]-2-(2-methylpropyl)benzoate Chemical compound C1=C(CC(C)C)C(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(C(=O)OC(C)(C)C)C[C@H](O)C1=CC=CN=C1 DLMAFWRGCFHXPU-LJAQVGFWSA-N 0.000 description 1
- JFTHXBCXELBRKS-MHZLTWQESA-N methyl 4-[4-[2-[[(2r)-2-hydroxy-2-pyridin-3-ylethyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]phenyl]-2-propan-2-ylsulfanylbenzoate Chemical compound C1=C(SC(C)C)C(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(C(=O)OC(C)(C)C)C[C@H](O)C1=CC=CN=C1 JFTHXBCXELBRKS-MHZLTWQESA-N 0.000 description 1
- NYMPKIWBKZNTTN-UHFFFAOYSA-N methyl 4-[4-[2-[benzyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]phenyl]-2-nitrobenzoate Chemical compound C1=C([N+]([O-])=O)C(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(C(=O)OC(C)(C)C)CC1=CC=CC=C1 NYMPKIWBKZNTTN-UHFFFAOYSA-N 0.000 description 1
- JYHBALPATYFQBD-UHFFFAOYSA-N methyl 4-[4-[2-[benzyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]phenyl]-3-nitrobenzoate Chemical compound [O-][N+](=O)C1=CC(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(C(=O)OC(C)(C)C)CC1=CC=CC=C1 JYHBALPATYFQBD-UHFFFAOYSA-N 0.000 description 1
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- RRYUVFWAKFOWLU-PMERELPUSA-N methyl 4-[4-[2-[benzyl-[(2r)-2-hydroxy-2-phenylethyl]amino]ethyl]phenyl]-2-nitrobenzoate Chemical compound C1=C([N+]([O-])=O)C(C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN(CC=1C=CC=CC=1)C[C@H](O)C1=CC=CC=C1 RRYUVFWAKFOWLU-PMERELPUSA-N 0.000 description 1
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- KPJJTGRBQMNBAZ-WOJBJXKFSA-N tert-butyl n-[(2r)-1-hydroxy-3-(4-iodophenyl)propan-2-yl]-n-[(2s)-2-hydroxy-2-phenylethyl]carbamate Chemical compound C1([C@H](O)CN(C(=O)OC(C)(C)C)[C@@H](CO)CC=2C=CC(I)=CC=2)=CC=CC=C1 KPJJTGRBQMNBAZ-WOJBJXKFSA-N 0.000 description 1
- ZEHSVXLTWICYPX-IBGZPJMESA-N tert-butyl n-[(2r)-2-(3-chlorophenyl)-2-hydroxyethyl]-n-[2-(4-iodophenoxy)ethyl]carbamate Chemical compound C([C@H](O)C=1C=C(Cl)C=CC=1)N(C(=O)OC(C)(C)C)CCOC1=CC=C(I)C=C1 ZEHSVXLTWICYPX-IBGZPJMESA-N 0.000 description 1
- KNMPODGXPVOVIU-HKBQPEDESA-N tert-butyl n-[(2r)-2-(4-aminophenyl)-2-hydroxyethyl]-n-[2-[4-[3-cyclohexyloxy-4-(methylsulfonylcarbamoyl)phenyl]phenyl]ethyl]carbamate Chemical compound C([C@H](O)C=1C=CC(N)=CC=1)N(C(=O)OC(C)(C)C)CCC(C=C1)=CC=C1C(C=1)=CC=C(C(=O)NS(C)(=O)=O)C=1OC1CCCCC1 KNMPODGXPVOVIU-HKBQPEDESA-N 0.000 description 1
- CBXLCRHZFWBOCM-HKBQPEDESA-N tert-butyl n-[(2r)-2-(4-aminophenyl)-2-hydroxyethyl]-n-[2-[4-[3-cyclopentyl-4-(methylsulfonylcarbamoyl)phenyl]phenyl]ethyl]carbamate Chemical compound C([C@H](O)C=1C=CC(N)=CC=1)N(C(=O)OC(C)(C)C)CCC(C=C1)=CC=C1C(C=1)=CC=C(C(=O)NS(C)(=O)=O)C=1C1CCCC1 CBXLCRHZFWBOCM-HKBQPEDESA-N 0.000 description 1
- FSNQXCAIEMZKIM-YTTGMZPUSA-N tert-butyl n-[(2r)-2-(4-aminophenyl)-2-hydroxyethyl]-n-[3-[4-[3-cyclohexyloxy-4-(methylsulfonylcarbamoyl)phenyl]phenyl]propyl]carbamate Chemical compound C([C@H](O)C=1C=CC(N)=CC=1)N(C(=O)OC(C)(C)C)CCCC(C=C1)=CC=C1C(C=1)=CC=C(C(=O)NS(C)(=O)=O)C=1OC1CCCCC1 FSNQXCAIEMZKIM-YTTGMZPUSA-N 0.000 description 1
- AGNRSHSQWJQDIX-YTTGMZPUSA-N tert-butyl n-[(2r)-2-(4-aminophenyl)-2-hydroxyethyl]-n-[3-[4-[3-cyclopentyl-4-(methylsulfonylcarbamoyl)phenyl]phenyl]propyl]carbamate Chemical compound C([C@H](O)C=1C=CC(N)=CC=1)N(C(=O)OC(C)(C)C)CCCC(C=C1)=CC=C1C(C=1)=CC=C(C(=O)NS(C)(=O)=O)C=1C1CCCC1 AGNRSHSQWJQDIX-YTTGMZPUSA-N 0.000 description 1
- BWEKPXVNWZROSA-LJAQVGFWSA-N tert-butyl n-[(2r)-2-(4-aminophenyl)-2-hydroxyethyl]-n-[3-[4-[4-(methylsulfonylcarbamoyl)-3-propan-2-yloxyphenyl]phenyl]propyl]carbamate Chemical compound C1=C(C(=O)NS(C)(=O)=O)C(OC(C)C)=CC(C=2C=CC(CCCN(C[C@H](O)C=3C=CC(N)=CC=3)C(=O)OC(C)(C)C)=CC=2)=C1 BWEKPXVNWZROSA-LJAQVGFWSA-N 0.000 description 1
- PYRSVLZHVHEQLU-LJAQVGFWSA-N tert-butyl n-[(2r)-2-(6-chloropyridin-3-yl)-2-hydroxyethyl]-n-[2-[4-[3-cyclohexyloxy-4-(methylsulfonylcarbamoyl)phenyl]phenoxy]ethyl]carbamate Chemical compound C([C@H](O)C=1C=NC(Cl)=CC=1)N(C(=O)OC(C)(C)C)CCOC(C=C1)=CC=C1C(C=1)=CC=C(C(=O)NS(C)(=O)=O)C=1OC1CCCCC1 PYRSVLZHVHEQLU-LJAQVGFWSA-N 0.000 description 1
- XYSFPYZEZAEBBY-MHZLTWQESA-N tert-butyl n-[(2r)-2-(6-chloropyridin-3-yl)-2-hydroxyethyl]-n-[2-[4-[4-(methylsulfonylcarbamoyl)-3-(propan-2-ylamino)phenyl]phenyl]ethyl]carbamate Chemical compound C1=C(C(=O)NS(C)(=O)=O)C(NC(C)C)=CC(C=2C=CC(CCN(C[C@H](O)C=3C=NC(Cl)=CC=3)C(=O)OC(C)(C)C)=CC=2)=C1 XYSFPYZEZAEBBY-MHZLTWQESA-N 0.000 description 1
- UHCSOXKTHFJNJH-LJAQVGFWSA-N tert-butyl n-[(2r)-2-hydroxy-2-phenylethyl]-n-[2-[4-[3-(2-methylpropoxy)-4-(methylsulfonylcarbamoyl)phenyl]phenyl]ethyl]carbamate Chemical compound C1=C(C(=O)NS(C)(=O)=O)C(OCC(C)C)=CC(C=2C=CC(CCN(C[C@H](O)C=3C=CC=CC=3)C(=O)OC(C)(C)C)=CC=2)=C1 UHCSOXKTHFJNJH-LJAQVGFWSA-N 0.000 description 1
- DAUNFAOAIGNVDV-HKBQPEDESA-N tert-butyl n-[(2r)-2-hydroxy-2-phenylethyl]-n-[2-[4-[3-(3-methylbutyl)-4-(methylsulfonylcarbamoyl)phenyl]phenyl]ethyl]carbamate Chemical compound C1=C(C(=O)NS(C)(=O)=O)C(CCC(C)C)=CC(C=2C=CC(CCN(C[C@H](O)C=3C=CC=CC=3)C(=O)OC(C)(C)C)=CC=2)=C1 DAUNFAOAIGNVDV-HKBQPEDESA-N 0.000 description 1
- GCSZFOWJKFXKPN-PMERELPUSA-N tert-butyl n-[(2r)-2-hydroxy-2-phenylethyl]-n-[2-[4-[3-propan-2-yloxy-4-(propylsulfonylcarbamoyl)phenyl]phenyl]ethyl]carbamate Chemical compound C1=C(OC(C)C)C(C(=O)NS(=O)(=O)CCC)=CC=C1C(C=C1)=CC=C1CCN(C(=O)OC(C)(C)C)C[C@H](O)C1=CC=CC=C1 GCSZFOWJKFXKPN-PMERELPUSA-N 0.000 description 1
- CXBNXNOBQCHREP-NDEPHWFRSA-N tert-butyl n-[(2r)-2-hydroxy-2-phenylethyl]-n-[2-[4-[4-(methylsulfonylcarbamoyl)-3-propan-2-yloxyphenyl]phenoxy]ethyl]carbamate Chemical compound C1=C(C(=O)NS(C)(=O)=O)C(OC(C)C)=CC(C=2C=CC(OCCN(C[C@H](O)C=3C=CC=CC=3)C(=O)OC(C)(C)C)=CC=2)=C1 CXBNXNOBQCHREP-NDEPHWFRSA-N 0.000 description 1
- WSQWDAPZMYWNCG-NDEPHWFRSA-N tert-butyl n-[(2r)-2-hydroxy-2-pyridin-3-ylethyl]-n-[2-[4-[4-(methylsulfonylcarbamoyl)-3-(propan-2-ylamino)phenyl]phenyl]ethyl]carbamate Chemical compound C1=C(C(=O)NS(C)(=O)=O)C(NC(C)C)=CC(C=2C=CC(CCN(C[C@H](O)C=3C=NC=CC=3)C(=O)OC(C)(C)C)=CC=2)=C1 WSQWDAPZMYWNCG-NDEPHWFRSA-N 0.000 description 1
- MKACTOFCNRNAMJ-LJAQVGFWSA-N tert-butyl n-[(2r)-2-hydroxy-2-pyridin-3-ylethyl]-n-[3-[4-[3-(2-methylpropoxy)-4-(methylsulfonylcarbamoyl)phenyl]phenyl]propyl]carbamate Chemical compound C1=C(C(=O)NS(C)(=O)=O)C(OCC(C)C)=CC(C=2C=CC(CCCN(C[C@H](O)C=3C=NC=CC=3)C(=O)OC(C)(C)C)=CC=2)=C1 MKACTOFCNRNAMJ-LJAQVGFWSA-N 0.000 description 1
- VLVLMBAWCKGIJQ-YWZLYKJASA-N tert-butyl n-[2-(4-bromophenyl)ethyl]-n-[(1r,2s)-1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl]carbamate Chemical compound C1([C@@H](O)[C@H](C)N(CCC=2C=CC(Br)=CC=2)C(=O)OC(C)(C)C)=CC=C(O)C=C1 VLVLMBAWCKGIJQ-YWZLYKJASA-N 0.000 description 1
- MUZQTHLBMBNOOV-UXMRNZNESA-N tert-butyl n-[2-(4-bromophenyl)ethyl]-n-[(2r)-2-(oxan-2-yloxy)-2-phenylethyl]carbamate Chemical compound C([C@H](OC1OCCCC1)C=1C=CC=CC=1)N(C(=O)OC(C)(C)C)CCC1=CC=C(Br)C=C1 MUZQTHLBMBNOOV-UXMRNZNESA-N 0.000 description 1
- NVBIEJIOLLQCGG-SFHVURJKSA-N tert-butyl n-[2-(4-bromophenyl)ethyl]-n-[(2r)-2-hydroxy-2-pyridin-3-ylethyl]carbamate Chemical compound C([C@H](O)C=1C=NC=CC=1)N(C(=O)OC(C)(C)C)CCC1=CC=C(Br)C=C1 NVBIEJIOLLQCGG-SFHVURJKSA-N 0.000 description 1
- RIVHJNJKFGVQBV-KNPJQLEMSA-N tert-butyl n-[2-[4-(3-cyclohexyloxy-4-sulfamoylphenyl)phenyl]ethyl]-n-[(2r)-2-(oxan-2-yloxy)-2-phenylethyl]carbamate Chemical compound C([C@H](OC1OCCCC1)C=1C=CC=CC=1)N(C(=O)OC(C)(C)C)CCC(C=C1)=CC=C1C(C=1)=CC=C(S(N)(=O)=O)C=1OC1CCCCC1 RIVHJNJKFGVQBV-KNPJQLEMSA-N 0.000 description 1
- WIJILVSEIOPBSR-MHZLTWQESA-N tert-butyl n-[2-[4-[3-(2-fluoroethoxy)-4-(methylsulfonylcarbamoyl)phenyl]phenyl]ethyl]-n-[(2r)-2-hydroxy-2-phenylethyl]carbamate Chemical compound C([C@H](O)C=1C=CC=CC=1)N(C(=O)OC(C)(C)C)CCC(C=C1)=CC=C1C1=CC=C(C(=O)NS(C)(=O)=O)C(OCCF)=C1 WIJILVSEIOPBSR-MHZLTWQESA-N 0.000 description 1
- HLILISXNZZSYOX-JHOBJCJYSA-N tert-butyl n-[2-[4-[3-(3-fluoropropoxy)-4-(methylsulfonylcarbamoyl)phenyl]phenyl]ethyl]-n-[(1r,2s)-1-hydroxy-1-phenylpropan-2-yl]carbamate Chemical compound C1([C@@H](O)[C@H](C)N(CCC=2C=CC(=CC=2)C=2C=C(OCCCF)C(C(=O)NS(C)(=O)=O)=CC=2)C(=O)OC(C)(C)C)=CC=CC=C1 HLILISXNZZSYOX-JHOBJCJYSA-N 0.000 description 1
- XQHZNCUPTYGHKU-HKBQPEDESA-N tert-butyl n-[2-[4-[3-cyclohexyloxy-4-(methylsulfonylcarbamoyl)phenyl]phenoxy]ethyl]-n-[(2r)-2-hydroxy-2-phenylethyl]carbamate Chemical compound C([C@H](O)C=1C=CC=CC=1)N(C(=O)OC(C)(C)C)CCOC(C=C1)=CC=C1C(C=1)=CC=C(C(=O)NS(C)(=O)=O)C=1OC1CCCCC1 XQHZNCUPTYGHKU-HKBQPEDESA-N 0.000 description 1
- LWZVCOVQLWETRK-HKBQPEDESA-N tert-butyl n-[2-[4-[3-cyclohexyloxy-4-(methylsulfonylcarbamoyl)phenyl]phenyl]ethyl]-n-[(2r)-2-hydroxy-2-(3-nitrophenyl)ethyl]carbamate Chemical compound C([C@H](O)C=1C=C(C=CC=1)[N+]([O-])=O)N(C(=O)OC(C)(C)C)CCC(C=C1)=CC=C1C(C=1)=CC=C(C(=O)NS(C)(=O)=O)C=1OC1CCCCC1 LWZVCOVQLWETRK-HKBQPEDESA-N 0.000 description 1
- OXTMJDKSXLYUIQ-HKBQPEDESA-N tert-butyl n-[2-[4-[3-cyclohexyloxy-4-[2-(methanesulfonamido)-2-oxoethyl]phenyl]phenyl]ethyl]-n-[(2r)-2-hydroxy-2-pyridin-3-ylethyl]carbamate Chemical compound C([C@H](O)C=1C=NC=CC=1)N(C(=O)OC(C)(C)C)CCC(C=C1)=CC=C1C(C=1)=CC=C(CC(=O)NS(C)(=O)=O)C=1OC1CCCCC1 OXTMJDKSXLYUIQ-HKBQPEDESA-N 0.000 description 1
- RFCZPVNPWNLYCP-HKBQPEDESA-N tert-butyl n-[2-[4-[3-cyclopentyl-4-(methylsulfonylcarbamoyl)phenyl]phenoxy]ethyl]-n-[(2r)-2-hydroxy-2-(4-nitrophenyl)ethyl]carbamate Chemical compound C([C@H](O)C=1C=CC(=CC=1)[N+]([O-])=O)N(C(=O)OC(C)(C)C)CCOC(C=C1)=CC=C1C(C=1)=CC=C(C(=O)NS(C)(=O)=O)C=1C1CCCC1 RFCZPVNPWNLYCP-HKBQPEDESA-N 0.000 description 1
- RZYLVWRASDGEFX-PMERELPUSA-N tert-butyl n-[2-[4-[3-cyclopentyloxy-4-(methylsulfonylcarbamoyl)phenyl]phenoxy]ethyl]-n-[(2r)-2-hydroxy-2-phenylethyl]carbamate Chemical compound C([C@H](O)C=1C=CC=CC=1)N(C(=O)OC(C)(C)C)CCOC(C=C1)=CC=C1C(C=1)=CC=C(C(=O)NS(C)(=O)=O)C=1OC1CCCC1 RZYLVWRASDGEFX-PMERELPUSA-N 0.000 description 1
- HMMDEYMFAGRQGX-MHZLTWQESA-N tert-butyl n-[2-[4-[3-ethoxy-4-(methylsulfonylcarbamoyl)phenyl]phenoxy]ethyl]-n-[(2r)-2-hydroxy-2-phenylethyl]carbamate Chemical compound C1=C(C(=O)NS(C)(=O)=O)C(OCC)=CC(C=2C=CC(OCCN(C[C@H](O)C=3C=CC=CC=3)C(=O)OC(C)(C)C)=CC=2)=C1 HMMDEYMFAGRQGX-MHZLTWQESA-N 0.000 description 1
- COGZJCHFWSGZCI-XIFFEERXSA-N tert-butyl n-[2-[4-[4-(benzenesulfonylcarbamoyl)-3-propan-2-yloxyphenyl]phenyl]ethyl]-n-[(2r)-2-hydroxy-2-phenylethyl]carbamate Chemical compound CC(C)OC1=CC(C=2C=CC(CCN(C[C@H](O)C=3C=CC=CC=3)C(=O)OC(C)(C)C)=CC=2)=CC=C1C(=O)NS(=O)(=O)C1=CC=CC=C1 COGZJCHFWSGZCI-XIFFEERXSA-N 0.000 description 1
- CFSQEXQGTCJPNC-QNGWXLTQSA-N tert-butyl n-[2-[4-[4-(benzylsulfonylcarbamoyl)-3-cyclohexyloxyphenyl]phenyl]ethyl]-n-[(2r)-2-hydroxy-2-phenylethyl]carbamate Chemical compound C([C@H](O)C=1C=CC=CC=1)N(C(=O)OC(C)(C)C)CCC(C=C1)=CC=C1C(C=C1OC2CCCCC2)=CC=C1C(=O)NS(=O)(=O)CC1=CC=CC=C1 CFSQEXQGTCJPNC-QNGWXLTQSA-N 0.000 description 1
- DHBFXSURFXUPEU-UMSFTDKQSA-N tert-butyl n-[2-[4-[4-(cyclohexylmethylsulfonylcarbamoyl)-3-propan-2-yloxyphenyl]phenyl]ethyl]-n-[(2r)-2-hydroxy-2-phenylethyl]carbamate Chemical compound CC(C)OC1=CC(C=2C=CC(CCN(C[C@H](O)C=3C=CC=CC=3)C(=O)OC(C)(C)C)=CC=2)=CC=C1C(=O)NS(=O)(=O)CC1CCCCC1 DHBFXSURFXUPEU-UMSFTDKQSA-N 0.000 description 1
- DCGXPNITKZMCLT-PMERELPUSA-N tert-butyl n-[2-[4-[4-formyl-3-[methyl(propan-2-yl)amino]phenyl]phenyl]ethyl]-n-[(2r)-2-hydroxy-2-phenylethyl]carbamate Chemical compound C1=C(C=O)C(N(C)C(C)C)=CC(C=2C=CC(CCN(C[C@H](O)C=3C=CC=CC=3)C(=O)OC(C)(C)C)=CC=2)=C1 DCGXPNITKZMCLT-PMERELPUSA-N 0.000 description 1
- WIAIVBFVTDIIER-YTTGMZPUSA-N tert-butyl n-[3-[4-[3-cyclohexyloxy-4-(methylsulfonylcarbamoyl)phenyl]phenyl]propyl]-n-[(2r)-2-hydroxy-2-(4-nitrophenyl)ethyl]carbamate Chemical compound C([C@H](O)C=1C=CC(=CC=1)[N+]([O-])=O)N(C(=O)OC(C)(C)C)CCCC(C=C1)=CC=C1C(C=1)=CC=C(C(=O)NS(C)(=O)=O)C=1OC1CCCCC1 WIAIVBFVTDIIER-YTTGMZPUSA-N 0.000 description 1
- VDJWCZQEIOJZEI-YTTGMZPUSA-N tert-butyl n-[3-[4-[3-cyclohexyloxy-4-(methylsulfonylcarbamoyl)phenyl]phenyl]propyl]-n-[(2r)-2-hydroxy-2-phenylethyl]carbamate Chemical compound C([C@H](O)C=1C=CC=CC=1)N(C(=O)OC(C)(C)C)CCCC(C=C1)=CC=C1C(C=1)=CC=C(C(=O)NS(C)(=O)=O)C=1OC1CCCCC1 VDJWCZQEIOJZEI-YTTGMZPUSA-N 0.000 description 1
- XHARGCMWPVVNEE-UMSFTDKQSA-N tert-butyl n-[3-[4-[3-cyclohexyloxy-4-(propylsulfonylcarbamoyl)phenyl]phenyl]propyl]-n-[(2r)-2-hydroxy-2-phenylethyl]carbamate Chemical compound CCCS(=O)(=O)NC(=O)C1=CC=C(C=2C=CC(CCCN(C[C@H](O)C=3C=CC=CC=3)C(=O)OC(C)(C)C)=CC=2)C=C1OC1CCCCC1 XHARGCMWPVVNEE-UMSFTDKQSA-N 0.000 description 1
- FAMUEZOJZXUSDQ-YTTGMZPUSA-N tert-butyl n-[3-[4-[3-cyclopentyl-4-(methylsulfonylcarbamoyl)phenyl]phenyl]propyl]-n-[(2r)-2-hydroxy-2-phenylethyl]carbamate Chemical compound C([C@H](O)C=1C=CC=CC=1)N(C(=O)OC(C)(C)C)CCCC(C=C1)=CC=C1C(C=1)=CC=C(C(=O)NS(C)(=O)=O)C=1C1CCCC1 FAMUEZOJZXUSDQ-YTTGMZPUSA-N 0.000 description 1
- PJUFNGOLTSWJHJ-NDEPHWFRSA-N tert-butyl n-[3-[4-[3-ethoxy-4-(methylsulfonylcarbamoyl)phenyl]phenyl]propyl]-n-[(2r)-2-hydroxy-2-phenylethyl]carbamate Chemical compound C1=C(C(=O)NS(C)(=O)=O)C(OCC)=CC(C=2C=CC(CCCN(C[C@H](O)C=3C=CC=CC=3)C(=O)OC(C)(C)C)=CC=2)=C1 PJUFNGOLTSWJHJ-NDEPHWFRSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 230000000699 topical effect Effects 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
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- SIOVKLKJSOKLIF-HJWRWDBZSA-N trimethylsilyl (1z)-n-trimethylsilylethanimidate Chemical compound C[Si](C)(C)OC(/C)=N\[Si](C)(C)C SIOVKLKJSOKLIF-HJWRWDBZSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 206010046494 urge incontinence Diseases 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/56—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in ortho-position
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
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- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/16—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
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- C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
- C07C311/51—Y being a hydrogen or a carbon atom
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
- C07C323/63—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2003907111A AU2003907111A0 (en) | 2003-12-23 | Aminoalcohol Derivatives | |
| AU2003907111 | 2003-12-23 | ||
| PCT/JP2004/019495 WO2005061433A2 (en) | 2003-12-23 | 2004-12-20 | Aminoalcohol derivatives |
Publications (2)
| Publication Number | Publication Date |
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| CA2551167A1 CA2551167A1 (en) | 2005-07-07 |
| CA2551167C true CA2551167C (en) | 2011-10-18 |
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| Application Number | Title | Priority Date | Filing Date |
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| CA2551167A Expired - Fee Related CA2551167C (en) | 2003-12-23 | 2004-12-20 | Aminoalcohol derivatives |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US7417060B2 (enExample) |
| EP (1) | EP1697301A2 (enExample) |
| JP (1) | JP4618250B2 (enExample) |
| KR (1) | KR101071748B1 (enExample) |
| CN (1) | CN100582088C (enExample) |
| AR (1) | AR047351A1 (enExample) |
| CA (1) | CA2551167C (enExample) |
| MX (1) | MXPA06007173A (enExample) |
| TW (1) | TW200526551A (enExample) |
| WO (1) | WO2005061433A2 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| RU2319698C2 (ru) * | 2002-06-27 | 2008-03-20 | Астеллас Фарма Инк. | АЛЬФА-ФЕНИЛ ИЛИ ПИРИДИЛ-ЭТАНОЛАМИНЫ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ АГОНИСТОВ β3 АДРЕНЕРГИЧЕСКИХ РЕЦЕПТОРОВ |
| ES2308142T3 (es) | 2003-02-14 | 2008-12-01 | Kissei Pharmaceutical Co., Ltd. | Derivados aminoalcohol, composiciones farmaceuticas que los contienen, y sus usos. |
| EP1679304A4 (en) | 2003-10-24 | 2006-11-15 | Kissei Pharmaceutical | AMINO ALCOHOL DERIVATIVE, MEDICAL COMPOSITION CONTAINING THEREOF AND ITS USE |
| JP4618250B2 (ja) | 2003-12-23 | 2011-01-26 | アステラス製薬株式会社 | アミノアルコール誘導体 |
| JPWO2006022237A1 (ja) * | 2004-08-24 | 2008-05-08 | キッセイ薬品工業株式会社 | 脂肪肝の予防または治療剤 |
| KR101052462B1 (ko) * | 2004-09-21 | 2011-07-28 | 아스텔라스세이야쿠 가부시키가이샤 | 아미노알콜 유도체 |
| EP1860098B1 (en) * | 2005-03-16 | 2012-11-14 | Toyama Chemical Co., Ltd. | Novel anthranilic acid derivative or salt thereof |
| KR100901664B1 (ko) | 2007-08-06 | 2009-06-09 | 주식회사 오스코텍 | β-아미노알콜 유도체, 이의 제조방법 및 이를유효성분으로 함유하는 TNF-α 매개성 질환의 예방 및치료용 약학적 조성물 |
| PL3365321T3 (pl) * | 2015-10-23 | 2024-03-25 | B3Ar Therapeutics, Inc. | Jon obojnaczy solabegronu i jego zastosowania |
| CN116640074B (zh) * | 2023-05-22 | 2025-09-23 | 河北允升精细化工有限公司 | 一种合成5-氯-2-(2-氯乙氧基)苯磺酰胺的方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3718638A1 (de) * | 1987-06-04 | 1988-12-22 | Thomae Gmbh Dr K | Neue phenylethanolamine, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| NO179246C (no) * | 1991-11-20 | 1996-09-04 | Sankyo Co | Aromatiske amino-alkoholderivater og mellomprodukter til fremstilling derav |
| WO1996035671A1 (en) * | 1995-05-10 | 1996-11-14 | Pfizer Inc. | β-ADRENERGIC AGONISTS |
| GB9812709D0 (en) * | 1998-06-13 | 1998-08-12 | Glaxo Group Ltd | Chemical compounds |
| EP1326861A1 (en) * | 2000-10-20 | 2003-07-16 | Pfizer Products Inc. | Alpha-aryl ethanolamines and their use as beta-3 adrenergic receptor agonists |
| JP2005518357A (ja) * | 2001-11-20 | 2005-06-23 | イーライ・リリー・アンド・カンパニー | ベータ3アドレナリンアゴニスト |
| DOP2003000587A (es) * | 2002-02-27 | 2003-08-30 | Pfizer Prod Inc | AGONISTAS DEL RECEPTOR ß3-ADRENERGICO |
| AU2003248352A1 (en) * | 2002-02-27 | 2003-09-09 | Pfizer Products Inc. | PROCESSES AND INTERMEDIATES USEFUL IN PREPARING Beta3-ADRENERGIC RECEPTOR AGONISTS |
| WO2003076397A1 (en) * | 2002-03-14 | 2003-09-18 | Fujisawa Pharmaceutical Co., Ltd. | Aminoalcohol derivatives as beta-3 adrenergic receptor agonists |
| RU2319698C2 (ru) * | 2002-06-27 | 2008-03-20 | Астеллас Фарма Инк. | АЛЬФА-ФЕНИЛ ИЛИ ПИРИДИЛ-ЭТАНОЛАМИНЫ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ АГОНИСТОВ β3 АДРЕНЕРГИЧЕСКИХ РЕЦЕПТОРОВ |
| AU2002952839A0 (en) * | 2002-11-21 | 2002-12-05 | Fujisawa Pharmaceutical Co., Ltd. | Aminoalcohol derivatives |
| ES2308142T3 (es) * | 2003-02-14 | 2008-12-01 | Kissei Pharmaceutical Co., Ltd. | Derivados aminoalcohol, composiciones farmaceuticas que los contienen, y sus usos. |
| JP4618250B2 (ja) | 2003-12-23 | 2011-01-26 | アステラス製薬株式会社 | アミノアルコール誘導体 |
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2004
- 2004-12-20 JP JP2006520478A patent/JP4618250B2/ja not_active Expired - Fee Related
- 2004-12-20 KR KR1020067014417A patent/KR101071748B1/ko not_active Expired - Fee Related
- 2004-12-20 EP EP04807850A patent/EP1697301A2/en not_active Withdrawn
- 2004-12-20 MX MXPA06007173A patent/MXPA06007173A/es active IP Right Grant
- 2004-12-20 CN CN200480041150A patent/CN100582088C/zh not_active Expired - Fee Related
- 2004-12-20 CA CA2551167A patent/CA2551167C/en not_active Expired - Fee Related
- 2004-12-20 WO PCT/JP2004/019495 patent/WO2005061433A2/en not_active Ceased
- 2004-12-21 US US11/016,886 patent/US7417060B2/en not_active Expired - Fee Related
- 2004-12-22 TW TW093139942A patent/TW200526551A/zh unknown
- 2004-12-27 AR ARP040104909A patent/AR047351A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20070019678A (ko) | 2007-02-15 |
| JP4618250B2 (ja) | 2011-01-26 |
| MXPA06007173A (es) | 2006-08-23 |
| KR101071748B1 (ko) | 2011-10-11 |
| CA2551167A1 (en) | 2005-07-07 |
| JP2007516211A (ja) | 2007-06-21 |
| EP1697301A2 (en) | 2006-09-06 |
| US20050137236A1 (en) | 2005-06-23 |
| WO2005061433A2 (en) | 2005-07-07 |
| TW200526551A (en) | 2005-08-16 |
| CN1906154A (zh) | 2007-01-31 |
| WO2005061433A3 (en) | 2005-10-27 |
| US7417060B2 (en) | 2008-08-26 |
| CN100582088C (zh) | 2010-01-20 |
| AR047351A1 (es) | 2006-01-18 |
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