DE10106214A1 - Neue Alkyl-phenylimino-imidazolidin-Derivate zur Behandlung der Harninkontinenz - Google Patents
Neue Alkyl-phenylimino-imidazolidin-Derivate zur Behandlung der HarninkontinenzInfo
- Publication number
- DE10106214A1 DE10106214A1 DE10106214A DE10106214A DE10106214A1 DE 10106214 A1 DE10106214 A1 DE 10106214A1 DE 10106214 A DE10106214 A DE 10106214A DE 10106214 A DE10106214 A DE 10106214A DE 10106214 A1 DE10106214 A1 DE 10106214A1
- Authority
- DE
- Germany
- Prior art keywords
- iminoimidazolidine
- phen
- isopropyl
- tert
- methyl
- 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.)
- Withdrawn
Links
- 206010046543 Urinary incontinence Diseases 0.000 title claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 47
- 229910052801 chlorine Inorganic materials 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 229910052794 bromium Inorganic materials 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 20
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- DISXFZWKRTZTRI-UHFFFAOYSA-N 4,5-dihydro-1h-imidazol-2-amine Chemical compound NC1=NCCN1 DISXFZWKRTZTRI-UHFFFAOYSA-N 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 2
- 208000026533 urinary bladder disease Diseases 0.000 claims 2
- MSYFITFSZJKRQJ-UHFFFAOYSA-N 4,5-dihydroimidazol-1-amine Chemical compound NN1CCN=C1 MSYFITFSZJKRQJ-UHFFFAOYSA-N 0.000 claims 1
- 208000029162 bladder disease Diseases 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 4
- 125000001424 substituent group Chemical group 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 239000000126 substance Substances 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 239000000460 chlorine Substances 0.000 description 13
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 13
- 239000012074 organic phase Substances 0.000 description 13
- 239000000203 mixture Substances 0.000 description 11
- 239000000843 powder Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 238000010992 reflux Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 206010021639 Incontinence Diseases 0.000 description 6
- 239000000556 agonist Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 230000004060 metabolic process Effects 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 150000002460 imidazoles Chemical class 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 206010066218 Stress Urinary Incontinence Diseases 0.000 description 4
- 210000000748 cardiovascular system Anatomy 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 230000008602 contraction Effects 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 4
- MRRMWDRBFHYYLS-UHFFFAOYSA-N 2-methyl-3-propan-2-ylaniline Chemical compound CC(C)C1=CC=CC(N)=C1C MRRMWDRBFHYYLS-UHFFFAOYSA-N 0.000 description 3
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229960002896 clonidine Drugs 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- -1 imido Chemical group 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- RLHOIKPZBFJZLO-UHFFFAOYSA-N (5-tert-butyl-2-methoxyphenyl)thiourea Chemical compound COC1=CC=C(C(C)(C)C)C=C1NC(N)=S RLHOIKPZBFJZLO-UHFFFAOYSA-N 0.000 description 2
- HPQVXLJSJCOYFE-UHFFFAOYSA-N 1-(2-methyl-3-nitrophenyl)ethanone Chemical compound CC(=O)C1=CC=CC([N+]([O-])=O)=C1C HPQVXLJSJCOYFE-UHFFFAOYSA-N 0.000 description 2
- XRGZUSXNHIQMNA-UHFFFAOYSA-N 1-(3-amino-2-methylphenyl)ethanone Chemical compound CC(=O)C1=CC=CC(N)=C1C XRGZUSXNHIQMNA-UHFFFAOYSA-N 0.000 description 2
- UENLNPJRTOHQIC-UHFFFAOYSA-N 2-methyl-3-nitrobenzoyl chloride Chemical compound CC1=C(C(Cl)=O)C=CC=C1[N+]([O-])=O UENLNPJRTOHQIC-UHFFFAOYSA-N 0.000 description 2
- BXMAHVHRBZCSOZ-UHFFFAOYSA-N 2-methyl-3-prop-1-en-2-ylaniline Chemical compound CC(=C)C1=CC=CC(N)=C1C BXMAHVHRBZCSOZ-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- 241000282465 Canis Species 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- ICKWRNNAJNRFQF-UHFFFAOYSA-N diethyl 2-(2-methyl-3-nitrobenzoyl)propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)C(=O)C1=CC=CC([N+]([O-])=O)=C1C ICKWRNNAJNRFQF-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 125000001841 imino group Chemical group [H]N=* 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 210000003903 pelvic floor Anatomy 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 208000022170 stress incontinence Diseases 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 210000003708 urethra Anatomy 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- AAWQRCSXONUDTD-UHFFFAOYSA-N 1-(2-methylsulfanylimidazolidin-1-yl)ethanone Chemical compound CSC1NCCN1C(C)=O AAWQRCSXONUDTD-UHFFFAOYSA-N 0.000 description 1
- BWOJKFHBUFPMBT-UHFFFAOYSA-N 1-methyl-5-propan-2-ylcyclohexa-2,4-dien-1-amine Chemical compound CC(C)C1=CC=CC(C)(N)C1 BWOJKFHBUFPMBT-UHFFFAOYSA-N 0.000 description 1
- YPQAFWHSMWWPLX-UHFFFAOYSA-N 1975-50-4 Chemical compound CC1=C(C(O)=O)C=CC=C1[N+]([O-])=O YPQAFWHSMWWPLX-UHFFFAOYSA-N 0.000 description 1
- RABBMOYULJIAFU-UHFFFAOYSA-N 1h-pyrrole;thiophene Chemical class C=1C=CNC=1.C=1C=CSC=1 RABBMOYULJIAFU-UHFFFAOYSA-N 0.000 description 1
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
- PTKSEFOSCHHMPD-SNVBAGLBSA-N 2-amino-n-[(2s)-2-(2,5-dimethoxyphenyl)-2-hydroxyethyl]acetamide Chemical compound COC1=CC=C(OC)C([C@H](O)CNC(=O)CN)=C1 PTKSEFOSCHHMPD-SNVBAGLBSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- DLTLFDQLMFMTRQ-UHFFFAOYSA-N 5-tert-butyl-2-methoxyaniline Chemical compound COC1=CC=C(C(C)(C)C)C=C1N DLTLFDQLMFMTRQ-UHFFFAOYSA-N 0.000 description 1
- 108060003345 Adrenergic Receptor Proteins 0.000 description 1
- 102000017910 Adrenergic receptor Human genes 0.000 description 1
- HNUALPPJLMYHDK-UHFFFAOYSA-N C[CH]C Chemical compound C[CH]C HNUALPPJLMYHDK-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 108010001237 Cytochrome P-450 CYP2D6 Proteins 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 208000000921 Urge Urinary Incontinence Diseases 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 102000030619 alpha-1 Adrenergic Receptor Human genes 0.000 description 1
- 108020004102 alpha-1 Adrenergic Receptor Proteins 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000035606 childbirth Effects 0.000 description 1
- 150000001804 chlorine Chemical class 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- VFRCNXKYZVQYLX-UHFFFAOYSA-N deglymidodrine Chemical compound COC1=CC=C(OC)C(C(O)CN)=C1 VFRCNXKYZVQYLX-UHFFFAOYSA-N 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 230000030214 innervation Effects 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 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
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 235000011147 magnesium chloride Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- 229960001094 midodrine Drugs 0.000 description 1
- YEPNQNIIERDOCM-UHFFFAOYSA-N n-phenylimidazol-2-imine Chemical class N1=CC=NC1=NC1=CC=CC=C1 YEPNQNIIERDOCM-UHFFFAOYSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 239000004533 oil dispersion Substances 0.000 description 1
- 208000024449 overflow incontinence Diseases 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
- 229960001802 phenylephrine Drugs 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- RFAKLMBNSZNUNX-UHFFFAOYSA-N potassium;isothiocyanate Chemical compound [K+].[N-]=C=S RFAKLMBNSZNUNX-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 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 1
- 230000011514 reflex Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000005070 sphincter Anatomy 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 206010046494 urge incontinence Diseases 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Priority Applications (23)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10106214A DE10106214A1 (de) | 2001-02-10 | 2001-02-10 | Neue Alkyl-phenylimino-imidazolidin-Derivate zur Behandlung der Harninkontinenz |
| PCT/EP2002/000576 WO2002064570A1 (de) | 2001-02-10 | 2002-01-22 | Neue alkyl-phenylimino-imidazolidin-derivate zur behandlung der harninkontinenz |
| EEP200300379A EE200300379A (et) | 2001-02-10 | 2002-01-22 | Alküülfenüüliminoimidasolidiini derivaadid uriinipidamatuse ravimiseks |
| BR0206949-0A BR0206949A (pt) | 2001-02-10 | 2002-01-22 | Derivados de alquil-fenilimino-imidazolidina para tratamento de incontinência urinária |
| EA200300835A EA200300835A1 (ru) | 2001-02-10 | 2002-01-22 | Новые производные алкилфенилиминоимидазолидина для лечения недержания мочи |
| MXPA03007127A MXPA03007127A (es) | 2001-02-10 | 2002-01-22 | Nuevos derivados de alquil-fenilimino-imidazolidina para tratamiento de incontinencia urinaria. |
| CA002437809A CA2437809A1 (en) | 2001-02-10 | 2002-01-22 | Novel alkyl phenylimino-imidazolidine derivatives for treating urinary incontinence |
| CZ20032146A CZ20032146A3 (cs) | 2001-02-10 | 2002-01-22 | Imidazolidinové deriváty a jejich použití |
| CNA02804570XA CN1491216A (zh) | 2001-02-10 | 2002-01-22 | 用于治疗尿失禁的新颖烷基苯基亚氨咪唑烷衍生物 |
| IL15729702A IL157297A0 (en) | 2001-02-10 | 2002-01-22 | Novel alkyl phenylimino-imidazolidine derivatives for treating urinary incontinence |
| KR10-2003-7010280A KR20030076653A (ko) | 2001-02-10 | 2002-01-22 | 요실금의 치료를 위한 신규한알킬-페닐이미노-이미다졸리딘 유도체 |
| HU0303004A HUP0303004A3 (en) | 2001-02-10 | 2002-01-22 | Novel alkyl phenylimino-imidazolidine derivatives, pharmaceutical compositions containing them and their use for preparation of for treating urinary incontinence |
| PL36214902A PL362149A1 (en) | 2001-02-10 | 2002-01-22 | Novel alkyl phenylimino-imidazolidine derivatives for treating urinary incontinence |
| EP02704665A EP1362038A1 (de) | 2001-02-10 | 2002-01-22 | Neue alkyl-phenylimino-imidazolidin-derivate zur behandlung der harninkontinenz |
| JP2002564503A JP2004517963A (ja) | 2001-02-10 | 2002-01-22 | 尿失禁治療用の新規なアルキル−フェニルイミノイミダゾリジン誘導体 |
| SK1013-2003A SK10132003A3 (sk) | 2001-02-10 | 2002-01-22 | Alkylfenyliminoimidazolidínové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie |
| US10/058,456 US20020169193A1 (en) | 2001-02-10 | 2002-01-28 | Alkylphenyliminoimidazolidine derivatives for treating urinary incontinence |
| ARP020100417A AR035226A1 (es) | 2001-02-10 | 2002-02-08 | Derivados de alquil-fenilimino-imidazolidina para el tratamiento de la incontinencia urinaria. |
| ZA200305609A ZA200305609B (en) | 2001-02-10 | 2003-07-21 | Novel-alkyl-phenylimino-imidazolidine derivatives for treating urinary incontinence. |
| EC2003004700A ECSP034700A (es) | 2001-02-10 | 2003-07-22 | Nuevos derivados de m-alquil-fenilimino-imidazolidana para tratar la incontinencia urinaria |
| BG108036A BG108036A (bg) | 2001-02-10 | 2003-07-28 | Нови алкил-фенилимино-имидазолидинови производни за лечение на инконтиненция |
| NO20033368A NO20033368D0 (no) | 2001-02-10 | 2003-07-28 | Nye alkyl-fenylimino-imidazolidin-derivater for behandling av urin-inkontinens |
| US11/006,375 US20050085522A1 (en) | 2001-02-10 | 2004-12-07 | Alkylphenyliminoimidazolidine derivatives for treating urinary incontinence |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10106214A DE10106214A1 (de) | 2001-02-10 | 2001-02-10 | Neue Alkyl-phenylimino-imidazolidin-Derivate zur Behandlung der Harninkontinenz |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE10106214A1 true DE10106214A1 (de) | 2002-08-14 |
Family
ID=7673601
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE10106214A Withdrawn DE10106214A1 (de) | 2001-02-10 | 2001-02-10 | Neue Alkyl-phenylimino-imidazolidin-Derivate zur Behandlung der Harninkontinenz |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP1362038A1 (et) |
| JP (1) | JP2004517963A (et) |
| KR (1) | KR20030076653A (et) |
| CN (1) | CN1491216A (et) |
| AR (1) | AR035226A1 (et) |
| BG (1) | BG108036A (et) |
| BR (1) | BR0206949A (et) |
| CA (1) | CA2437809A1 (et) |
| CZ (1) | CZ20032146A3 (et) |
| DE (1) | DE10106214A1 (et) |
| EA (1) | EA200300835A1 (et) |
| EC (1) | ECSP034700A (et) |
| EE (1) | EE200300379A (et) |
| HU (1) | HUP0303004A3 (et) |
| IL (1) | IL157297A0 (et) |
| MX (1) | MXPA03007127A (et) |
| NO (1) | NO20033368D0 (et) |
| PL (1) | PL362149A1 (et) |
| SK (1) | SK10132003A3 (et) |
| WO (1) | WO2002064570A1 (et) |
| ZA (1) | ZA200305609B (et) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1660484B1 (en) * | 2003-05-09 | 2008-08-27 | F. Hoffmann-La Roche Ag | Methyl indoles and methyl pyrrolopyridines as alpha-1 adrenergic agonists |
| JP4168086B1 (ja) * | 2008-04-16 | 2008-10-22 | 国立大学法人福井大学 | イミダゾリン誘導体 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3202660A (en) * | 1961-10-09 | 1965-08-24 | Boehringer Sohn Ingelheim | Process for the preparation of 3-arylamino-1, 3-diazacycloalkenes |
| DE3518604A1 (de) * | 1984-05-23 | 1985-11-28 | Egyt Gyógyszervegyészeti Gyár, Budapest | Verfahren zur herstellung von 2-(phenylimino)-imidazolidinderivaten |
| WO1996032939A1 (de) * | 1995-04-20 | 1996-10-24 | Boehringer Ingelheim Kg | VERWENDUNG VON α1L-AGONISTEN ZUR BEHANDLUNG DER HARNINKONTINENZ |
| WO1998042679A1 (fr) * | 1997-03-20 | 1998-10-01 | Sanofi-Synthelabo | Derives de benzenesulfonamide, leur preparation et leur application en therapeutique |
| US5952362A (en) * | 1997-06-23 | 1999-09-14 | Syntex (U.S.A) Inc. | 2-imidazoline, 2-oxazoline, 2-thiazoline, and 4-imidazole derivatives of methylphenyl, methoxyphenyl, and aminophenyl alkylsulfonamides and ureas and their use |
-
2001
- 2001-02-10 DE DE10106214A patent/DE10106214A1/de not_active Withdrawn
-
2002
- 2002-01-22 EP EP02704665A patent/EP1362038A1/de not_active Withdrawn
- 2002-01-22 BR BR0206949-0A patent/BR0206949A/pt not_active Application Discontinuation
- 2002-01-22 CA CA002437809A patent/CA2437809A1/en not_active Abandoned
- 2002-01-22 CZ CZ20032146A patent/CZ20032146A3/cs unknown
- 2002-01-22 JP JP2002564503A patent/JP2004517963A/ja active Pending
- 2002-01-22 SK SK1013-2003A patent/SK10132003A3/sk unknown
- 2002-01-22 KR KR10-2003-7010280A patent/KR20030076653A/ko not_active Withdrawn
- 2002-01-22 EE EEP200300379A patent/EE200300379A/et unknown
- 2002-01-22 IL IL15729702A patent/IL157297A0/xx unknown
- 2002-01-22 WO PCT/EP2002/000576 patent/WO2002064570A1/de not_active Ceased
- 2002-01-22 CN CNA02804570XA patent/CN1491216A/zh active Pending
- 2002-01-22 EA EA200300835A patent/EA200300835A1/ru unknown
- 2002-01-22 HU HU0303004A patent/HUP0303004A3/hu unknown
- 2002-01-22 MX MXPA03007127A patent/MXPA03007127A/es unknown
- 2002-01-22 PL PL36214902A patent/PL362149A1/xx not_active Application Discontinuation
- 2002-02-08 AR ARP020100417A patent/AR035226A1/es not_active Application Discontinuation
-
2003
- 2003-07-21 ZA ZA200305609A patent/ZA200305609B/en unknown
- 2003-07-22 EC EC2003004700A patent/ECSP034700A/es unknown
- 2003-07-28 NO NO20033368A patent/NO20033368D0/no not_active Application Discontinuation
- 2003-07-28 BG BG108036A patent/BG108036A/bg unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3202660A (en) * | 1961-10-09 | 1965-08-24 | Boehringer Sohn Ingelheim | Process for the preparation of 3-arylamino-1, 3-diazacycloalkenes |
| DE3518604A1 (de) * | 1984-05-23 | 1985-11-28 | Egyt Gyógyszervegyészeti Gyár, Budapest | Verfahren zur herstellung von 2-(phenylimino)-imidazolidinderivaten |
| WO1996032939A1 (de) * | 1995-04-20 | 1996-10-24 | Boehringer Ingelheim Kg | VERWENDUNG VON α1L-AGONISTEN ZUR BEHANDLUNG DER HARNINKONTINENZ |
| WO1998042679A1 (fr) * | 1997-03-20 | 1998-10-01 | Sanofi-Synthelabo | Derives de benzenesulfonamide, leur preparation et leur application en therapeutique |
| US5952362A (en) * | 1997-06-23 | 1999-09-14 | Syntex (U.S.A) Inc. | 2-imidazoline, 2-oxazoline, 2-thiazoline, and 4-imidazole derivatives of methylphenyl, methoxyphenyl, and aminophenyl alkylsulfonamides and ureas and their use |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002064570A1 (de) | 2002-08-22 |
| HUP0303004A2 (hu) | 2003-12-29 |
| CN1491216A (zh) | 2004-04-21 |
| EP1362038A1 (de) | 2003-11-19 |
| PL362149A1 (en) | 2004-10-18 |
| NO20033368L (no) | 2003-07-28 |
| AR035226A1 (es) | 2004-05-05 |
| BR0206949A (pt) | 2004-02-25 |
| CZ20032146A3 (cs) | 2003-12-17 |
| ZA200305609B (en) | 2004-04-29 |
| HUP0303004A3 (en) | 2004-07-28 |
| ECSP034700A (es) | 2003-08-29 |
| SK10132003A3 (sk) | 2004-02-03 |
| CA2437809A1 (en) | 2002-08-22 |
| MXPA03007127A (es) | 2003-11-18 |
| KR20030076653A (ko) | 2003-09-26 |
| EE200300379A (et) | 2003-12-15 |
| IL157297A0 (en) | 2004-02-19 |
| EA200300835A1 (ru) | 2004-02-26 |
| NO20033368D0 (no) | 2003-07-28 |
| JP2004517963A (ja) | 2004-06-17 |
| BG108036A (bg) | 2004-12-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE2634288B2 (et) | ||
| DD147943A5 (de) | Verfahren zur herstellung von alkyl-imidazol-derivaten | |
| CH646426A5 (en) | Process for the preparation of hydantoin derivatives | |
| EP0538783B1 (de) | N-phenyl-2-cyano-3-hydroxycrotonsäureamidderivate und deren Verwendung als Arzneimittel mit immunmodulatorischer Eigenschaft | |
| WO2001044164A1 (de) | Substituierte norbornylamino-derivate, verfahren zu ihrer herstellung, ihre verwendung als medikament oder diagnostikum sowie sie enthaltendes medikament | |
| DE2938990C2 (et) | ||
| DE2460929C2 (et) | ||
| DE2656088A1 (de) | Neues benzylalkoholderivat und verfahren zu seiner herstellung | |
| DE60025270T2 (de) | N-substituierte benzyl oder phenyl arylsulfamide und ihre verwendung | |
| DE10106214A1 (de) | Neue Alkyl-phenylimino-imidazolidin-Derivate zur Behandlung der Harninkontinenz | |
| DE2535599C2 (de) | Substituierte Zimtsäureamide, Verfahren zu ihrer Herstellung und pharmazeutische Zubereitungen, welche diese Verbindungen enthalten | |
| DE2746550C2 (et) | ||
| DD209628A5 (de) | Verfahren zur herstellung von imidazolinderivaten | |
| EP0160173B1 (de) | Benzothiazolderivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltendes Arzneimittel | |
| CH641444A5 (de) | N,n'-bis(n-cyano-n'-alkynyl)methanimidamidyl)cystamine sowie verfahren zu ihrer herstellung. | |
| DE2342312A1 (de) | Substituierte 2-hydroxyguanidino-carbamate | |
| DE3207023A1 (de) | Amidinverbindungen, verfahren zu ihrer herstellung und antikomplement-mittel, die diese verbindungen enthalten | |
| EP1328517A2 (de) | Neue m-amino-phenylimino-imidazolidin-derivate zur behandlung der harninkontinenz | |
| DD144764A5 (de) | Verfahren zur herstellung von r-n-(2-phenyl-2-hydroxyethyl)-3-phenylpropylaminen | |
| DE2009387C2 (de) | Anilin-acetamidine und ihre nichttoxischen Säureadditionssalze, Verfahren zu ihrer Herstellung und pharmazeutische Zubereitungen, welche diese Verbindungen enthalten | |
| DE2530515A1 (de) | Thienopyridinerivate, verfahren zu ihrer herstellung und sie enthaltende arzneimittelzubereitungen | |
| DE2903458A1 (de) | Phenylpyrol-derivate | |
| AT255034B (de) | Verfahren zur Herstellung von O, S-Dialkoxycarbonylthiaminen | |
| DE69215900T2 (de) | Cyclopropyl-n-hydroxyharnstoff als lypoxygenaseinhibitoren | |
| DE2116252A1 (de) | Dihydrotnazine, ihre Saureadditions salze und N Acyldenvate, Verfahren zu ihrer Herstellung und Arzneimittel, die diese Verbindungen als Wirkstoffe ent halten |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OM8 | Search report available as to paragraph 43 lit. 1 sentence 1 patent law | ||
| 8127 | New person/name/address of the applicant |
Owner name: BOEHRINGER INGELHEIM PHARMA GMBH & CO.KG, 55218 IN |
|
| 8141 | Disposal/no request for examination |