KR100536095B1 - 3,3-디페닐-프로필아민의 신규한 유도체의 안정한 염 - Google Patents
3,3-디페닐-프로필아민의 신규한 유도체의 안정한 염 Download PDFInfo
- Publication number
- KR100536095B1 KR100536095B1 KR10-2002-7006306A KR20027006306A KR100536095B1 KR 100536095 B1 KR100536095 B1 KR 100536095B1 KR 20027006306 A KR20027006306 A KR 20027006306A KR 100536095 B1 KR100536095 B1 KR 100536095B1
- Authority
- KR
- South Korea
- Prior art keywords
- acid
- phenyl
- propyl
- diisopropylamino
- formula
- Prior art date
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- 150000003839 salts Chemical class 0.000 title abstract description 24
- KISZTEOELCMZPY-UHFFFAOYSA-N 3,3-diphenylpropylamine Chemical class C=1C=CC=CC=1C(CCN)C1=CC=CC=C1 KISZTEOELCMZPY-UHFFFAOYSA-N 0.000 title abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 57
- 150000002148 esters Chemical class 0.000 claims abstract description 10
- CWIFYQQOFPQJEW-JOCHJYFZSA-N 2-[2-[(1r)-3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl]-2-methylpropanoic acid Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(CO)C=2)C(C)(C)C(O)=O)=CC=CC=C1 CWIFYQQOFPQJEW-JOCHJYFZSA-N 0.000 claims abstract description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-M fumarate(1-) Chemical compound OC(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-M 0.000 claims description 4
- -1 R-(+)-2- (3-diisopropylamino-1-phenyl-propyl) -4-hydroxymethylphenylisobutyrate ester Chemical class 0.000 abstract description 32
- 238000000034 method Methods 0.000 abstract description 22
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 abstract description 20
- 238000002360 preparation method Methods 0.000 abstract description 14
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 abstract description 14
- 239000000543 intermediate Substances 0.000 abstract description 12
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 abstract description 11
- 239000000203 mixture Substances 0.000 abstract description 9
- 239000000047 product Substances 0.000 abstract description 7
- 239000013067 intermediate product Substances 0.000 abstract description 5
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical class C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 abstract description 4
- 238000009472 formulation Methods 0.000 abstract description 3
- 230000000144 pharmacologic effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- 239000002253 acid Substances 0.000 description 32
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- DUXZAXCGJSBGDW-HXUWFJFHSA-N Desfesoterodine Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(CO)C=2)O)=CC=CC=C1 DUXZAXCGJSBGDW-HXUWFJFHSA-N 0.000 description 14
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 12
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 12
- 239000013078 crystal Substances 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 150000007522 mineralic acids Chemical class 0.000 description 10
- 150000007524 organic acids Chemical class 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 8
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 8
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 8
- 239000001530 fumaric acid Substances 0.000 description 8
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 description 8
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 description 8
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical group OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 8
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 8
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 7
- GVKBRMPULOEHLO-HHHXNRCGSA-N [3-[(1r)-3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-phenylmethoxyphenyl]methanol Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(CO)C=2)OCC=2C=CC=CC=2)=CC=CC=C1 GVKBRMPULOEHLO-HHHXNRCGSA-N 0.000 description 7
- 238000010586 diagram Methods 0.000 description 7
- YRJYQILAWNHFTB-HHHXNRCGSA-N methyl 3-[(1r)-3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-phenylmethoxybenzoate Chemical compound C1([C@H](CCN(C(C)C)C(C)C)C=2C=CC=CC=2)=CC(C(=O)OC)=CC=C1OCC1=CC=CC=C1 YRJYQILAWNHFTB-HHHXNRCGSA-N 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 238000004809 thin layer chromatography Methods 0.000 description 7
- AGPKNHUKPQYLCB-IREOKEETSA-N (2R)-5-[di(propan-2-yl)amino]-2-[1-(4-hydroxyphenyl)ethyl]-2-methyl-3-phenylpentanoic acid Chemical compound C(C)(C)N(CCC(C1=CC=CC=C1)[C@](C(=O)O)(C(C1=CC=C(C=C1)O)C)C)C(C)C AGPKNHUKPQYLCB-IREOKEETSA-N 0.000 description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 6
- NGSWKAQJJWESNS-UHFFFAOYSA-N 4-coumaric acid Chemical compound OC(=O)C=CC1=CC=C(O)C=C1 NGSWKAQJJWESNS-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 235000011054 acetic acid Nutrition 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- BJEPYKJPYRNKOW-UWTATZPHSA-N (R)-malic acid Chemical compound OC(=O)[C@H](O)CC(O)=O BJEPYKJPYRNKOW-UWTATZPHSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-SZSCBOSDSA-N 2-[(1s)-1,2-dihydroxyethyl]-3,4-dihydroxy-2h-furan-5-one Chemical compound OC[C@H](O)C1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-SZSCBOSDSA-N 0.000 description 4
- HWKRAUXFMLQKLS-UHFFFAOYSA-N 2-oxidanylidenepropanoic acid Chemical compound CC(=O)C(O)=O.CC(=O)C(O)=O HWKRAUXFMLQKLS-UHFFFAOYSA-N 0.000 description 4
- WUECABRAWUKURJ-UHFFFAOYSA-N 3-(2-methyl-1h-indol-3-yl)-3-oxopropanenitrile Chemical compound C1=CC=C2C(C(=O)CC#N)=C(C)NC2=C1 WUECABRAWUKURJ-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 239000005711 Benzoic acid Substances 0.000 description 4
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
- 239000001358 L(+)-tartaric acid Substances 0.000 description 4
- 235000011002 L(+)-tartaric acid Nutrition 0.000 description 4
- FEWJPZIEWOKRBE-LWMBPPNESA-N L-(+)-Tartaric acid Natural products OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 4
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 4
- 239000002211 L-ascorbic acid Substances 0.000 description 4
- 235000000069 L-ascorbic acid Nutrition 0.000 description 4
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- FEWJPZIEWOKRBE-XIXRPRMCSA-N Mesotartaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-XIXRPRMCSA-N 0.000 description 4
- OKJIRPAQVSHGFK-UHFFFAOYSA-N N-acetylglycine Chemical compound CC(=O)NCC(O)=O OKJIRPAQVSHGFK-UHFFFAOYSA-N 0.000 description 4
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 4
- 235000021314 Palmitic acid Nutrition 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- 235000021355 Stearic acid Nutrition 0.000 description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- 229960005261 aspartic acid Drugs 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 235000010233 benzoic acid Nutrition 0.000 description 4
- AEMOLEFTQBMNLQ-UHFFFAOYSA-N beta-D-galactopyranuronic acid Natural products OC1OC(C(O)=O)C(O)C(O)C1O AEMOLEFTQBMNLQ-UHFFFAOYSA-N 0.000 description 4
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 4
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- 235000004515 gallic acid Nutrition 0.000 description 4
- AUONNNVJUCSETH-UHFFFAOYSA-N icosanoyl icosanoate Chemical compound CCCCCCCCCCCCCCCCCCCC(=O)OC(=O)CCCCCCCCCCCCCCCCCCC AUONNNVJUCSETH-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
- 239000011976 maleic acid Substances 0.000 description 4
- 229940098779 methanesulfonic acid Drugs 0.000 description 4
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 4
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 4
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 4
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- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 4
- 235000019260 propionic acid Nutrition 0.000 description 4
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 4
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- NLSNLUSGBGHEII-UHFFFAOYSA-N 2-acetamidoacetic acid Chemical compound CC(=O)NCC(O)=O.CC(=O)NCC(O)=O NLSNLUSGBGHEII-UHFFFAOYSA-N 0.000 description 3
- LAGDURGUNCQADL-UHFFFAOYSA-N 2-methylpropanoic acid;hydrochloride Chemical compound Cl.CC(C)C(O)=O LAGDURGUNCQADL-UHFFFAOYSA-N 0.000 description 3
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- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
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- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
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- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
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- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 239000012286 potassium permanganate Substances 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C219/00—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C219/26—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/46—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C215/48—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by hydroxy groups
- C07C215/54—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by hydroxy groups linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P13/10—Drugs for disorders of the urinary system of the bladder
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
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- A—HUMAN NECESSITIES
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C219/00—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C219/26—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C219/28—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton having amino groups bound to acyclic carbon atoms of the carbon skeleton
-
- 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
- C07C229/38—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to acyclic carbon atoms and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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Abstract
Description
Claims (30)
- R-(+)-2-(3-디이소프로필아미노-1-페닐-프로필)-4-하이드록시메틸페닐이소부티레이트 에스테르 하이드로젠 퓨마레이트인 것을 특징으로 하는 결정형(crystalline form)의 화합물.
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19955190A DE19955190A1 (de) | 1999-11-16 | 1999-11-16 | Stabile Salze neuartiger Derivate von 3,3-Diphenylpropylaminen |
DE19955190.1 | 1999-11-16 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020057018318A Division KR100563149B1 (ko) | 1999-11-16 | 2000-11-15 | 3,3-디페닐-프로필아민의 신규한 유도체의 안정한 염 |
KR10-2005-7001429A Division KR100486394B1 (ko) | 1999-11-16 | 2000-11-15 | 3,3-디페닐-프로필아민의 신규한 유도체의 안정한 염 |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20020059744A KR20020059744A (ko) | 2002-07-13 |
KR100536095B1 true KR100536095B1 (ko) | 2005-12-12 |
Family
ID=7929277
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
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KR1020057018318A KR100563149B1 (ko) | 1999-11-16 | 2000-11-15 | 3,3-디페닐-프로필아민의 신규한 유도체의 안정한 염 |
KR10-2002-7006306A KR100536095B1 (ko) | 1999-11-16 | 2000-11-15 | 3,3-디페닐-프로필아민의 신규한 유도체의 안정한 염 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020057018318A KR100563149B1 (ko) | 1999-11-16 | 2000-11-15 | 3,3-디페닐-프로필아민의 신규한 유도체의 안정한 염 |
Country Status (30)
Country | Link |
---|---|
US (1) | US6858650B1 (ko) |
EP (3) | EP1481964B1 (ko) |
JP (6) | JP4083431B2 (ko) |
KR (2) | KR100563149B1 (ko) |
CN (1) | CN1215045C (ko) |
AT (3) | ATE337293T1 (ko) |
AU (1) | AU778132B2 (ko) |
BR (1) | BRPI0015610C1 (ko) |
CA (1) | CA2389749C (ko) |
CY (2) | CY1106204T1 (ko) |
CZ (2) | CZ302497B6 (ko) |
DE (5) | DE29923134U1 (ko) |
DK (3) | DK1690536T3 (ko) |
EA (1) | EA005588B1 (ko) |
ES (3) | ES2236032T7 (ko) |
GE (1) | GEP20084430B (ko) |
HK (3) | HK1067114A1 (ko) |
HU (2) | HU228197B1 (ko) |
IL (2) | IL149567A0 (ko) |
IS (2) | IS2124B (ko) |
MX (1) | MXPA02004603A (ko) |
NO (2) | NO323920B1 (ko) |
NZ (1) | NZ519230A (ko) |
PL (1) | PL201422B1 (ko) |
PT (3) | PT1230209E (ko) |
SI (3) | SI1690536T1 (ko) |
SK (3) | SK288185B6 (ko) |
UA (2) | UA73324C2 (ko) |
WO (1) | WO2001035957A1 (ko) |
ZA (1) | ZA200203315B (ko) |
Families Citing this family (48)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0957073A1 (en) | 1998-05-12 | 1999-11-17 | Schwarz Pharma Ag | Novel derivatives of 3,3-diphenylpropylamines |
DE29923134U1 (de) * | 1999-11-16 | 2000-06-29 | Sanol Arznei Schwarz Gmbh | Stabile Salze neuartiger Derviate von 3,3-Diphenylpropylaminen |
DE10028443C1 (de) * | 2000-06-14 | 2002-05-29 | Sanol Arznei Schwarz Gmbh | Verfahren zur Herstellung von 3,3-Diarylpropylaminen, (R,S)- und (R)-4-Phenyl-2-chromanon-6-carbonsäure sowie (R)-4-Phenyl-2-chromanon-carbonsäure-cinchonidinsalz und deren Verwendung zur Herstellung eines rechtsdrehenden Hydroxybenzylalkohols und von pharmazeutischen Zusammensetzungen |
DE10315917A1 (de) * | 2003-04-08 | 2004-11-18 | Schwarz Pharma Ag | Hochreine Basen von 3,3-Diphenylpropylaminmonoestern |
DE10315878B4 (de) | 2003-04-08 | 2009-06-04 | Schwarz Pharma Ag | Vorrichtung zur transdermalen Verabreichung von Fesoterodin und Verwendung |
WO2005012227A2 (en) * | 2003-08-05 | 2005-02-10 | Ranbaxy Laboratories Limited | Process for preparation of 2-(3-diisopropylamino-1-phenylpropyl)-4-hydroxymethyl-phenol, a metabolite of tolterodine |
ES2235648B1 (es) * | 2003-12-22 | 2006-11-01 | Ragactives, S.L. | Procedimiento para la obtencion de tolterodina. |
US8034823B2 (en) * | 2005-02-22 | 2011-10-11 | Savvipharm Inc | Method of increasing drug oral bioavailability and compositions of less toxic orotate salts |
KR100647068B1 (ko) | 2005-09-15 | 2006-11-23 | 하나제약 주식회사 | 라세믹n,n-디이소프로필-3-(2-히드록시-5-메틸페닐)-3-페닐프로판아민의 제조방법 |
RU2397163C2 (ru) * | 2006-05-24 | 2010-08-20 | Пфайзер Лимитед | Способ получения производных бензопиран-2-ола |
EP1862449A1 (en) * | 2006-05-31 | 2007-12-05 | Schwarz Pharma Ltd. | A shortened synthesis of substituted hydroxymethyl phenols |
EA016399B1 (ru) * | 2006-05-31 | 2012-04-30 | Шварц Фарма Лтд. | Способ синтеза замещенных гидроксиметилфенолов |
IES20060424A2 (en) * | 2006-06-08 | 2007-10-31 | Schwarz Pharma Ltd | Accelerated synthesis of (3-Diisopropylamino-1-phenylpropyl)-4-(hydroxymethyl)phenol and its phenolic monoesters |
DE602007008389D1 (de) * | 2006-06-09 | 2010-09-23 | Schwarz Pharma Ltd | Synthese von phenolischen estern von hydroxymethylphenolen |
CN101466371B (zh) * | 2006-06-09 | 2011-10-05 | 施瓦茨制药有限公司 | 含非索罗定的稳定的药用组合物 |
US7807715B2 (en) | 2006-06-09 | 2010-10-05 | Ucb Pharma Gmbh | Pharmaceutical compositions comprising fesoterodine |
CA2647990C (en) * | 2006-06-12 | 2014-02-04 | Claus Meese | New chiral intermediate, process for producing the same and its use in the manufacture of tolterodine, fesoterodine, or the active metabolite thereof |
IES20060435A2 (en) | 2006-06-12 | 2007-12-12 | Schwarz Pharma Ltd | Shortened synthesis using paraformaldehyde or trioxane |
WO2009037569A2 (en) * | 2007-09-21 | 2009-03-26 | Actavis Group Ptc Ehf | An improved process for the preparation of fesoterodine |
WO2009044278A1 (en) * | 2007-10-01 | 2009-04-09 | Actavis Group Ptc Ehf | Amorphous fesoterodine fumarate |
EP2294047A2 (en) * | 2008-04-04 | 2011-03-16 | Actavis Group PTC EHF | Novel mandelate salt of fesoterodine |
EP2323967A2 (en) * | 2008-07-21 | 2011-05-25 | Actavis Group PTC EHF | Fesoterodine comprising a reduced amount of dehydroxyfesoterodine |
IT1392082B1 (it) * | 2008-12-10 | 2012-02-09 | Chemi Spa | Nuove forme solide della fesoterodina fumarato |
CA2761602C (en) | 2009-05-11 | 2015-07-07 | Ratiopharm Gmbh | Desfesoterodine in the form of a tartaric acid salt |
IT1394219B1 (it) | 2009-05-15 | 2012-06-01 | Chemi Spa | Metodo di preparazione di fesoterodina fumarato di elevata purezza. |
IT1394217B1 (it) * | 2009-05-15 | 2012-06-01 | Chemi Spa | Metodo di preparazione di fesoterodina e/o fesoterodina fumarato. |
KR20120053027A (ko) | 2009-09-03 | 2012-05-24 | 테바 기오기스제르갸르 자르트쾨렌 뮈쾨되 레스즈베니타르사사그 | 페소테로딘 푸마레이트 및 페소테로딘 염기의 결정형 |
IT1396373B1 (it) * | 2009-10-29 | 2012-11-19 | Dipharma Francis Srl | Procedimento per la preparazione di fesoterodina. |
EP2316432A1 (de) | 2009-10-30 | 2011-05-04 | ratiopharm GmbH | Zusammensetzung enthaltend Fesoterodin und Ballaststoffe |
US20110124903A1 (en) * | 2009-11-20 | 2011-05-26 | Actavis Group Ptc Ehf | Solid state forms of fesoterodine intermediates |
IT1397521B1 (it) * | 2009-12-21 | 2013-01-16 | Dipharma Francis Srl | Procedimento per la preparazione di fesoterodina con un basso contenuto di impurezze. |
IT1397920B1 (it) * | 2010-02-08 | 2013-02-04 | Dipharma Francis Srl | Forma cristallina di fesoterodina fumarato e procedimento per la sua preparazione |
WO2011117884A1 (en) | 2010-03-22 | 2011-09-29 | Cadila Healthcare Limited | Stable pharmaceutical compositions comprising fesoterodine |
CA2796877A1 (en) | 2010-04-30 | 2011-11-03 | Merck Sharp & Dohme Corp. | Novel beta 3 adrenergic receptor agonists |
US20110282094A1 (en) * | 2010-05-11 | 2011-11-17 | Intas Pharmaceuticals Limited | Process for preparation of phenolic monoesters of hydroxymethyl phenols |
WO2011145019A1 (en) * | 2010-05-17 | 2011-11-24 | Orchid Chemicals And Pharmaceuticals Limited | Improved process for diphenylpropylamine derivatives |
IT1401451B1 (it) | 2010-06-10 | 2013-07-26 | Chemi Spa | Nuovo processo di preparazione di 2-idrossi-4-fenil-3,4-diidro-2h-cromen-6-il-metanolo e (r)-2-[3-(diisopropilammino)-1-fenilpropil]-4-(idrossimetil)fenolo. |
WO2011158257A1 (en) | 2010-06-18 | 2011-12-22 | Panacea Biotec Ltd | Preparation process of fesoterodine and intermediates |
WO2012025941A2 (en) | 2010-08-25 | 2012-03-01 | Cadila Healthcare Limited | Processes for the preparation of fesoterodine |
IT1403094B1 (it) * | 2010-12-09 | 2013-10-04 | Dipharma Francis Srl | Procedimento per la preparazione di fesoterodina o un suo sale |
WO2012098560A2 (en) * | 2011-01-17 | 2012-07-26 | Msn Laboratories Limited | Process for the preparation of muscarinic receptor antagonist |
TWI520732B (zh) | 2011-01-18 | 2016-02-11 | 輝瑞有限公司 | 固體分子分散液 |
EP2508173A1 (en) | 2011-04-08 | 2012-10-10 | LEK Pharmaceuticals d.d. | Stabilized pharmaceutical composition comprising fesoterodine |
EP2508175A1 (en) | 2011-04-08 | 2012-10-10 | LEK Pharmaceuticals d.d. | Pharmaceutical composition comprising fesoterodine or a salt or a solvate thereof |
US9422228B2 (en) | 2012-05-04 | 2016-08-23 | Crystal Pharma, S.A.U. | Process for the preparation of optically pure fesoterodine derivatives |
ITMI20121232A1 (it) | 2012-07-16 | 2014-01-17 | Cambrex Profarmaco Milano Srl | Procedimento per la preparazione di 2-(3-n,n-diisopropilamino-1-fenilpropil)-4-idrossimetil-fenolo e suoi derivati |
TR201721437A2 (tr) | 2017-12-25 | 2019-07-22 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Fesoterodi̇ni̇n modi̇fi̇ye salim sağlayan formülasyonlari |
EP4237405A1 (en) * | 2020-10-27 | 2023-09-06 | Wella Germany GmbH | 2-methoxymethyl-p-phenylenediamine in cosmetic grade quality |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FI77018C (fi) * | 1980-11-14 | 1989-01-10 | Lilly Co Eli | Analogifoerfarande foer framstaellning av antidepressivt aktiv (-)-enantiomer av n-metyl-n-/3-(2-metylfenoxi) -3-fenylpropyl/amin och dess farmaceutiskt godtagbara salt. |
IL66831A0 (en) * | 1981-10-05 | 1982-12-31 | Kefalas As | Indane derivatives |
SE8800207D0 (sv) * | 1988-01-22 | 1988-01-22 | Kabivitrum Ab | Nya aminer, deras anvendning och framstellning |
DE69120699T2 (de) * | 1990-03-08 | 1997-01-09 | Fujisawa Pharmaceutical Co | N-Monosubstituierte Cyclopentenylamine, ein Verfahren zu ihrer Herstellung, und ihre Verwendung als Medikament |
JPH0483431A (ja) * | 1990-07-26 | 1992-03-17 | Seiko Epson Corp | 選択呼出受信機 |
SE9203318D0 (sv) * | 1992-11-06 | 1992-11-06 | Kabi Pharmacia Ab | Novel 3,3-diphenylpropylamines, their use and preparation |
SE9701144D0 (sv) * | 1997-03-27 | 1997-03-27 | Pharmacia & Upjohn Ab | Novel compounds, their use and preparation |
EP0957073A1 (en) | 1998-05-12 | 1999-11-17 | Schwarz Pharma Ag | Novel derivatives of 3,3-diphenylpropylamines |
DE29923134U1 (de) * | 1999-11-16 | 2000-06-29 | Sanol Arznei Schwarz Gmbh | Stabile Salze neuartiger Derviate von 3,3-Diphenylpropylaminen |
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