EP0000784B1 - 4-Hydroxy-2-Benzimidazolinon-derivate, Verfahren zu deren Herstellung sowie diese Verbindungen enthaltende Arzneimittel - Google Patents
4-Hydroxy-2-Benzimidazolinon-derivate, Verfahren zu deren Herstellung sowie diese Verbindungen enthaltende Arzneimittel Download PDFInfo
- Publication number
- EP0000784B1 EP0000784B1 EP78100633A EP78100633A EP0000784B1 EP 0000784 B1 EP0000784 B1 EP 0000784B1 EP 78100633 A EP78100633 A EP 78100633A EP 78100633 A EP78100633 A EP 78100633A EP 0000784 B1 EP0000784 B1 EP 0000784B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- general formula
- compound
- hydroxy
- tert
- group
- 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
Links
- 238000000034 method Methods 0.000 title claims description 18
- CPBGGIHYAYWNDD-UHFFFAOYSA-N 4-hydroxy-1,3-dihydrobenzimidazol-2-one Chemical class OC1=CC=CC2=C1NC(=O)N2 CPBGGIHYAYWNDD-UHFFFAOYSA-N 0.000 title claims description 6
- 238000002360 preparation method Methods 0.000 title claims description 6
- 239000003814 drug Substances 0.000 title claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 74
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000006239 protecting group Chemical group 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims description 2
- 238000011282 treatment Methods 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
- -1 aminopropoxy side chain Chemical group 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 239000002253 acid Substances 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 6
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 6
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 6
- 238000000354 decomposition reaction Methods 0.000 description 6
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- BMMVEFDYSJTYLS-UHFFFAOYSA-N 3,4-dimethyl-2-nitro-6-(oxiran-2-ylmethoxy)aniline Chemical compound [O-][N+](=O)C1=C(C)C(C)=CC(OCC2OC2)=C1N BMMVEFDYSJTYLS-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- YEDAPLOEQXPKAP-UHFFFAOYSA-N 4-tert-butyl-2-nitro-6-(oxiran-2-ylmethoxy)aniline Chemical compound [O-][N+](=O)C1=CC(C(C)(C)C)=CC(OCC2OC2)=C1N YEDAPLOEQXPKAP-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 3
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 125000004432 carbon atom Chemical group C* 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
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 2
- BHMJRVRJABFHNG-UHFFFAOYSA-N (2-acetamido-4,5-dimethyl-3-nitrophenyl) acetate Chemical compound CC(=O)NC1=C(OC(C)=O)C=C(C)C(C)=C1[N+]([O-])=O BHMJRVRJABFHNG-UHFFFAOYSA-N 0.000 description 2
- BUUKYQKFPBCDJT-UHFFFAOYSA-N (2-acetamido-5-methyl-3-nitrophenyl) acetate Chemical compound CC(=O)NC1=C(OC(C)=O)C=C(C)C=C1[N+]([O-])=O BUUKYQKFPBCDJT-UHFFFAOYSA-N 0.000 description 2
- KZZFXNRSZXHCCJ-UHFFFAOYSA-N (6-acetamido-2,3-dihydro-1h-inden-5-yl) acetate Chemical compound C1=C(OC(C)=O)C(NC(=O)C)=CC2=C1CCC2 KZZFXNRSZXHCCJ-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- JGIFTMDPWQIWFI-UHFFFAOYSA-N 1-(2-amino-5-tert-butyl-3-nitrophenoxy)-3-(tert-butylamino)propan-2-ol Chemical compound CC(C)(C)NCC(O)COC1=CC(C(C)(C)C)=CC([N+]([O-])=O)=C1N JGIFTMDPWQIWFI-UHFFFAOYSA-N 0.000 description 2
- SBNMHIVUBZGKPD-UHFFFAOYSA-N 1-(tert-butylamino)-3-(2,3-diamino-5-methylphenoxy)propan-2-ol;trihydrochloride Chemical compound Cl.Cl.Cl.CC1=CC(N)=C(N)C(OCC(O)CNC(C)(C)C)=C1 SBNMHIVUBZGKPD-UHFFFAOYSA-N 0.000 description 2
- XQRIIZNTOKFIBU-UHFFFAOYSA-N 2-[(4-methyl-2,3-dinitrophenoxy)methyl]oxirane Chemical compound [O-][N+](=O)C1=C([N+]([O-])=O)C(C)=CC=C1OCC1OC1 XQRIIZNTOKFIBU-UHFFFAOYSA-N 0.000 description 2
- HCPJEHJGFKWRFM-UHFFFAOYSA-N 2-amino-5-methylphenol Chemical compound CC1=CC=C(N)C(O)=C1 HCPJEHJGFKWRFM-UHFFFAOYSA-N 0.000 description 2
- HFCOMOKKPQIADM-UHFFFAOYSA-N 2-amino-5-tert-butylphenol Chemical compound CC(C)(C)C1=CC=C(N)C(O)=C1 HFCOMOKKPQIADM-UHFFFAOYSA-N 0.000 description 2
- HIQCTHFRLRVNPP-UHFFFAOYSA-N 4-methyl-2,3-dinitrophenol Chemical compound CC1=CC=C(O)C([N+]([O-])=O)=C1[N+]([O-])=O HIQCTHFRLRVNPP-UHFFFAOYSA-N 0.000 description 2
- MTCYZSMODJVVFJ-UHFFFAOYSA-N 4-methyl-2-nitro-6-(oxiran-2-ylmethoxy)aniline Chemical compound [O-][N+](=O)C1=CC(C)=CC(OCC2OC2)=C1N MTCYZSMODJVVFJ-UHFFFAOYSA-N 0.000 description 2
- CWQNPEWPVOJINM-UHFFFAOYSA-N 4-tert-butyl-7-[3-(tert-butylamino)-2-hydroxypropoxy]-1,3-dihydrobenzimidazol-2-one Chemical compound CC(C)(C)NCC(O)COC1=CC=C(C(C)(C)C)C2=C1NC(=O)N2 CWQNPEWPVOJINM-UHFFFAOYSA-N 0.000 description 2
- FQVUUPPMBGPBRL-UHFFFAOYSA-N 5-tert-butyl-2-nitrophenol Chemical compound CC(C)(C)C1=CC=C([N+]([O-])=O)C(O)=C1 FQVUUPPMBGPBRL-UHFFFAOYSA-N 0.000 description 2
- HTLLODRBNFYRKI-UHFFFAOYSA-N 6-amino-2,3-dihydro-1h-inden-5-ol Chemical compound C1=C(O)C(N)=CC2=C1CCC2 HTLLODRBNFYRKI-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- APKWQHZGPAVTBD-UHFFFAOYSA-N [1-(tert-butylamino)-3-[(6-methyl-2-oxo-1,3-dihydrobenzimidazol-4-yl)oxy]propan-2-yl] 2,2-dimethylpropanoate Chemical compound CC1=CC(OCC(CNC(C)(C)C)OC(=O)C(C)(C)C)=C2NC(=O)NC2=C1 APKWQHZGPAVTBD-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 229960001317 isoprenaline Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- AMTLYQYIQUZDDA-UHFFFAOYSA-N (2-acetamido-4,5-dimethylphenyl) acetate Chemical compound CC(=O)NC1=CC(C)=C(C)C=C1OC(C)=O AMTLYQYIQUZDDA-UHFFFAOYSA-N 0.000 description 1
- URELJNVCEBTCHA-UHFFFAOYSA-N (2-acetamido-5-tert-butyl-3-nitrophenyl) acetate Chemical compound CC(=O)NC1=C(OC(C)=O)C=C(C(C)(C)C)C=C1[N+]([O-])=O URELJNVCEBTCHA-UHFFFAOYSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- TYNIUVDPUHFEFS-UHFFFAOYSA-N (6-acetamido-7-nitro-2,3-dihydro-1h-inden-5-yl) acetate Chemical compound CC(=O)NC1=C(OC(C)=O)C=C2CCCC2=C1[N+]([O-])=O TYNIUVDPUHFEFS-UHFFFAOYSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-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
- SILNNFMWIMZVEQ-UHFFFAOYSA-N 1,3-dihydrobenzimidazol-2-one Chemical compound C1=CC=C2NC(O)=NC2=C1 SILNNFMWIMZVEQ-UHFFFAOYSA-N 0.000 description 1
- OSSMPVSNUDMMJU-UHFFFAOYSA-N 1-(2,3-diamino-4-methylphenoxy)-3-(propan-2-ylamino)propan-2-ol;trihydrochloride Chemical compound Cl.Cl.Cl.CC(C)NCC(O)COC1=CC=C(C)C(N)=C1N OSSMPVSNUDMMJU-UHFFFAOYSA-N 0.000 description 1
- BJAJMPKRUIXUMB-UHFFFAOYSA-N 1-(2,3-diamino-5-tert-butylphenoxy)-3-(propan-2-ylamino)propan-2-ol Chemical compound CC(C)NCC(O)COC1=CC(C(C)(C)C)=CC(N)=C1N BJAJMPKRUIXUMB-UHFFFAOYSA-N 0.000 description 1
- CEHUHOUFBONBBZ-UHFFFAOYSA-N 1-(2,3-diamino-5-tert-butylphenoxy)-3-(propan-2-ylamino)propan-2-ol;trihydrochloride Chemical compound Cl.Cl.Cl.CC(C)NCC(O)COC1=CC(C(C)(C)C)=CC(N)=C1N CEHUHOUFBONBBZ-UHFFFAOYSA-N 0.000 description 1
- HWYSJGZMFZBZGQ-UHFFFAOYSA-N 1-(2-amino-4,5-dimethyl-3-nitrophenoxy)-3-(tert-butylamino)propan-2-ol Chemical compound CC1=CC(OCC(O)CNC(C)(C)C)=C(N)C([N+]([O-])=O)=C1C HWYSJGZMFZBZGQ-UHFFFAOYSA-N 0.000 description 1
- HPJNVHRTALYSEF-UHFFFAOYSA-N 1-(2-amino-5-tert-butyl-3-nitrophenoxy)-3-(propan-2-ylamino)propan-2-ol Chemical compound CC(C)NCC(O)COC1=CC(C(C)(C)C)=CC([N+]([O-])=O)=C1N HPJNVHRTALYSEF-UHFFFAOYSA-N 0.000 description 1
- PSOUMYHXOBPLDF-UHFFFAOYSA-N 1-(tert-butylamino)-3-(2,3-diamino-4,5-dimethylphenoxy)propan-2-ol Chemical compound CC1=CC(OCC(O)CNC(C)(C)C)=C(N)C(N)=C1C PSOUMYHXOBPLDF-UHFFFAOYSA-N 0.000 description 1
- XMFQBAISOMYQHK-UHFFFAOYSA-N 1-(tert-butylamino)-3-(2,3-diamino-4,5-dimethylphenoxy)propan-2-ol;trihydrochloride Chemical compound Cl.Cl.Cl.CC1=CC(OCC(O)CNC(C)(C)C)=C(N)C(N)=C1C XMFQBAISOMYQHK-UHFFFAOYSA-N 0.000 description 1
- AJLQESNKUTZRAL-UHFFFAOYSA-N 1-(tert-butylamino)-3-(2,3-diamino-4-methylphenoxy)propan-2-ol Chemical compound CC1=CC=C(OCC(O)CNC(C)(C)C)C(N)=C1N AJLQESNKUTZRAL-UHFFFAOYSA-N 0.000 description 1
- CDEXELITYBWMFF-UHFFFAOYSA-N 1-(tert-butylamino)-3-(2,3-diamino-4-methylphenoxy)propan-2-ol;trihydrochloride Chemical compound Cl.Cl.Cl.CC1=CC=C(OCC(O)CNC(C)(C)C)C(N)=C1N CDEXELITYBWMFF-UHFFFAOYSA-N 0.000 description 1
- RCLDYWBTZYJRGN-UHFFFAOYSA-N 1-(tert-butylamino)-3-(2,3-diamino-5-tert-butylphenoxy)propan-2-ol Chemical compound CC(C)(C)NCC(O)COC1=CC(C(C)(C)C)=CC(N)=C1N RCLDYWBTZYJRGN-UHFFFAOYSA-N 0.000 description 1
- NKAAATUZCOBASS-UHFFFAOYSA-N 1-(tert-butylamino)-3-(2,3-diamino-5-tert-butylphenoxy)propan-2-ol;trihydrochloride Chemical compound Cl.Cl.Cl.CC(C)(C)NCC(O)COC1=CC(C(C)(C)C)=CC(N)=C1N NKAAATUZCOBASS-UHFFFAOYSA-N 0.000 description 1
- MLLCDDRZOJHLLR-UHFFFAOYSA-N 1-(tert-butylamino)-3-(5-methyl-5,6-dinitrocyclohexa-1,3-dien-1-yl)oxypropan-2-ol Chemical compound CC(C)(C)NCC(O)COC1=CC=CC(C)([N+]([O-])=O)C1[N+]([O-])=O MLLCDDRZOJHLLR-UHFFFAOYSA-N 0.000 description 1
- GMIBYSVPGPHIRJ-UHFFFAOYSA-N 1-(tert-butylamino)-3-[(6,7-diamino-2,3-dihydro-1h-inden-5-yl)oxy]propan-2-ol Chemical compound NC1=C(N)C(OCC(O)CNC(C)(C)C)=CC2=C1CCC2 GMIBYSVPGPHIRJ-UHFFFAOYSA-N 0.000 description 1
- QEALLRPDWUJYNW-UHFFFAOYSA-N 1-(tert-butylamino)-3-[(6,7-diamino-2,3-dihydro-1h-inden-5-yl)oxy]propan-2-ol;trihydrochloride Chemical compound Cl.Cl.Cl.NC1=C(N)C(OCC(O)CNC(C)(C)C)=CC2=C1CCC2 QEALLRPDWUJYNW-UHFFFAOYSA-N 0.000 description 1
- XDRHZZJERJGBJO-UHFFFAOYSA-N 1-[(6-amino-7-nitro-2,3-dihydro-1h-inden-5-yl)oxy]-3-(tert-butylamino)propan-2-ol Chemical compound [O-][N+](=O)C1=C(N)C(OCC(O)CNC(C)(C)C)=CC2=C1CCC2 XDRHZZJERJGBJO-UHFFFAOYSA-N 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- HVTQDSGGHBWVTR-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-phenylmethoxypyrazol-1-yl]-1-morpholin-4-ylethanone Chemical compound C(C1=CC=CC=C1)OC1=NN(C=C1C=1C=NC(=NC=1)NC1CC2=CC=CC=C2C1)CC(=O)N1CCOCC1 HVTQDSGGHBWVTR-UHFFFAOYSA-N 0.000 description 1
- JVGYGTMQKKLSOK-UHFFFAOYSA-N 2-amino-4,5-dimethyl-3-nitrophenol Chemical compound CC1=CC(O)=C(N)C([N+]([O-])=O)=C1C JVGYGTMQKKLSOK-UHFFFAOYSA-N 0.000 description 1
- JEASLLCHQHBBGM-UHFFFAOYSA-N 2-amino-4,5-dimethylphenol Chemical compound CC1=CC(N)=C(O)C=C1C JEASLLCHQHBBGM-UHFFFAOYSA-N 0.000 description 1
- MFRSIXFISYTVIT-UHFFFAOYSA-N 3-amino-4-methyl-1-naphthalen-1-yloxypentan-2-ol Chemical compound C1=CC=C2C(OCC(O)C(N)C(C)C)=CC=CC2=C1 MFRSIXFISYTVIT-UHFFFAOYSA-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
- IHPDAJPBLHBTTF-UHFFFAOYSA-N 4-[2-hydroxy-3-(propan-2-ylamino)propoxy]-6-methyl-1,3-dihydrobenzimidazol-2-one Chemical compound CC(C)NCC(O)COC1=CC(C)=CC2=C1NC(=O)N2 IHPDAJPBLHBTTF-UHFFFAOYSA-N 0.000 description 1
- ULYDCWAPJBHEIX-UHFFFAOYSA-N 4-[2-hydroxy-3-(propan-2-ylamino)propoxy]-7-methyl-1,3-dihydrobenzimidazol-2-one Chemical compound CC(C)NCC(O)COC1=CC=C(C)C2=C1NC(=O)N2 ULYDCWAPJBHEIX-UHFFFAOYSA-N 0.000 description 1
- GJHQPGOUBCJWJZ-UHFFFAOYSA-N 4-[3-(tert-butylamino)-2-hydroxypropoxy]-7-methyl-1,3-dihydrobenzimidazol-2-one Chemical compound CC1=CC=C(OCC(O)CNC(C)(C)C)C2=C1NC(=O)N2 GJHQPGOUBCJWJZ-UHFFFAOYSA-N 0.000 description 1
- ANAWRRAUQXSHKD-UHFFFAOYSA-N 4-[3-(tert-butylamino)-2-hydroxypropoxy]benzimidazol-2-one Chemical compound CC(C)(C)NCC(O)COC1=CC=CC2=NC(=O)N=C12 ANAWRRAUQXSHKD-UHFFFAOYSA-N 0.000 description 1
- JLLQXDVIQDVETJ-UHFFFAOYSA-N 4-nitro-6-(oxiran-2-ylmethoxy)-2,3-dihydro-1h-inden-5-amine Chemical compound C1=C2CCCC2=C([N+]([O-])=O)C(N)=C1OCC1CO1 JLLQXDVIQDVETJ-UHFFFAOYSA-N 0.000 description 1
- WTFUTSCZYYCBAY-SXBRIOAWSA-N 6-[(E)-C-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-N-hydroxycarbonimidoyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C/C(=N/O)/C1=CC2=C(NC(O2)=O)C=C1 WTFUTSCZYYCBAY-SXBRIOAWSA-N 0.000 description 1
- OWSCQLVYTZXRRP-UHFFFAOYSA-N 6-amino-7-nitro-2,3-dihydro-1h-inden-5-ol Chemical compound NC1=C(O)C=C2CCCC2=C1[N+]([O-])=O OWSCQLVYTZXRRP-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 241001136792 Alle Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- GRNMYORTJDTJLC-UHFFFAOYSA-N C(C)(=O)NC1=C(C=C(C=C1)C(C)(C)C)OC(C)=O.N1=CC=CC=C1 Chemical compound C(C)(=O)NC1=C(C=C(C=C1)C(C)(C)C)OC(C)=O.N1=CC=CC=C1 GRNMYORTJDTJLC-UHFFFAOYSA-N 0.000 description 1
- 0 C*[C@]1(C/C(/*)=C(\*)/C(/O*N(**)ON)=C\C(C)(C)C1)N Chemical compound C*[C@]1(C/C(/*)=C(\*)/C(/O*N(**)ON)=C\C(C)(C)C1)N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 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 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000000397 acetylating effect Effects 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 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
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- PJHUABJTDFXYRQ-UHFFFAOYSA-N benzoyl azide Chemical compound [N-]=[N+]=NC(=O)C1=CC=CC=C1 PJHUABJTDFXYRQ-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229920006158 high molecular weight polymer Polymers 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229960004592 isopropanol Drugs 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 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
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 230000000802 nitrating effect Effects 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 150000004987 o-phenylenediamines Chemical class 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 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
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles 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 in position 2
- C07D235/26—Oxygen atoms
Definitions
- DE-OS 2700193 describes 4-hydroxy-2-benzimidazolinone derivatives with a ⁇ -receptor blocking action, the fused benzene ring of which is unsubstituted.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2736295 | 1977-08-12 | ||
| DE2736295 | 1977-08-12 | ||
| DE2801953 | 1978-01-18 | ||
| DE19782801953 DE2801953A1 (de) | 1978-01-18 | 1978-01-18 | 4-hydroxy-2-benzimidazolinon-derivate, verfahren zu deren herstellung sowie diese verbindungen enthaltende arzneimittel |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP0000784A1 EP0000784A1 (de) | 1979-02-21 |
| EP0000784B1 true EP0000784B1 (de) | 1981-08-26 |
Family
ID=25772515
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP78100633A Expired EP0000784B1 (de) | 1977-08-12 | 1978-08-09 | 4-Hydroxy-2-Benzimidazolinon-derivate, Verfahren zu deren Herstellung sowie diese Verbindungen enthaltende Arzneimittel |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US4367235A (da) |
| EP (1) | EP0000784B1 (da) |
| JP (1) | JPS5432467A (da) |
| AT (1) | AT364831B (da) |
| AU (1) | AU3888578A (da) |
| CA (1) | CA1108619A (da) |
| DD (1) | DD137584A5 (da) |
| DE (1) | DE2860981D1 (da) |
| DK (1) | DK355378A (da) |
| ES (1) | ES472435A1 (da) |
| FI (1) | FI782452A7 (da) |
| IL (1) | IL55315A0 (da) |
| IT (1) | IT7826640A0 (da) |
| PT (1) | PT68404A (da) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0178413A1 (en) * | 1984-08-17 | 1986-04-23 | Beecham Group Plc | Benzimidazoles |
| US4554287A (en) * | 1984-09-12 | 1985-11-19 | Smithkline Beckman Corporation | Antihypertensive 7-[2-(dialkylamino)ethyl]-4-hydroxy-1,3-benzimidazol-2-ones |
| JPS63156809A (ja) * | 1986-12-19 | 1988-06-29 | Shin Etsu Chem Co Ltd | 塩化ビニル系重合体の製造方法 |
| CA2085844A1 (en) * | 1991-12-27 | 1993-06-28 | Nobuyuki Hamanaka | Fused benzeneoxyacetic acid derivatives |
| EP0711284A1 (en) * | 1993-07-31 | 1996-05-15 | Smithkline Beecham Plc | 2-benzoheterocyclyloxy or thiopropanolamine derivatives with adreno receptor agonist activity |
| ZA967892B (en) * | 1995-09-21 | 1998-03-18 | Lilly Co Eli | Selective β3 adrenergic agonists. |
| US5808080A (en) * | 1996-09-05 | 1998-09-15 | Eli Lilly And Company | Selective β3 adrenergic agonists |
| ES2171839T3 (es) | 1996-09-05 | 2002-09-16 | Lilly Co Eli | Analogos de carbazol como agonistas adrenergicos selectivos de beta3. |
| CO5011072A1 (es) * | 1997-12-05 | 2001-02-28 | Lilly Co Eli | Etanolaminas pirazinil substituidas como agfonistas de los receptores |
| CN103445428A (zh) * | 2012-05-28 | 2013-12-18 | 苏州科羽电子技术服务有限公司 | 一种车座手提袋 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4081447A (en) * | 1975-04-09 | 1978-03-28 | Abbott Laboratories | 5-[2-Hydroxy-3-(3,4-dimethoxy phenethylamino)]-propoxy-3,4-dihydro carbostyril and pharmaceutically acceptable salts thereof |
| CH624395A5 (da) * | 1976-01-08 | 1981-07-31 | Ciba Geigy Ag |
-
1978
- 1978-07-31 CA CA308,433A patent/CA1108619A/en not_active Expired
- 1978-08-08 PT PT68404A patent/PT68404A/pt unknown
- 1978-08-08 ES ES472435A patent/ES472435A1/es not_active Expired
- 1978-08-08 IL IL7855315A patent/IL55315A0/xx unknown
- 1978-08-09 EP EP78100633A patent/EP0000784B1/de not_active Expired
- 1978-08-09 DE DE7878100633T patent/DE2860981D1/de not_active Expired
- 1978-08-09 DD DD78207192A patent/DD137584A5/xx unknown
- 1978-08-09 IT IT7826640A patent/IT7826640A0/it unknown
- 1978-08-10 FI FI782452A patent/FI782452A7/fi not_active Application Discontinuation
- 1978-08-10 AT AT0582978A patent/AT364831B/de not_active IP Right Cessation
- 1978-08-11 JP JP9811278A patent/JPS5432467A/ja active Pending
- 1978-08-11 DK DK355378A patent/DK355378A/da not_active Application Discontinuation
- 1978-08-14 AU AU38885/78A patent/AU3888578A/en active Pending
-
1980
- 1980-07-18 US US06/171,940 patent/US4367235A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CA1108619A (en) | 1981-09-08 |
| ATA582978A (de) | 1981-04-15 |
| DK355378A (da) | 1979-02-13 |
| ES472435A1 (es) | 1979-04-16 |
| FI782452A7 (fi) | 1979-02-13 |
| JPS5432467A (en) | 1979-03-09 |
| DE2860981D1 (en) | 1981-11-19 |
| AU3888578A (en) | 1980-02-21 |
| IT7826640A0 (it) | 1978-08-09 |
| DD137584A5 (de) | 1979-09-12 |
| EP0000784A1 (de) | 1979-02-21 |
| US4367235A (en) | 1983-01-04 |
| IL55315A0 (en) | 1978-10-31 |
| PT68404A (de) | 1978-09-01 |
| AT364831B (de) | 1981-11-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE1695556C3 (de) | 3-Alkyl-1,2,3,4,4a,9-hexahydropyrazino[1,2-f]morphanthridinderivate | |
| EP0014951A2 (de) | Heterocyclische Oxypropanolamin-Derivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| DE3119874A1 (de) | "benzazepinderivate, ihre herstellung und ihre verwendung als arzneimittel" | |
| EP0000784B1 (de) | 4-Hydroxy-2-Benzimidazolinon-derivate, Verfahren zu deren Herstellung sowie diese Verbindungen enthaltende Arzneimittel | |
| AT368130B (de) | Verfahren zur herstellung von neuen 9-aminoalkyl- fluorenen und von deren salzen | |
| EP0014928A1 (de) | Neue Piperidinopropylderivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| DE2619164C2 (de) | Indazolyl-(4)-oxy-propanolamine, Verfahren zu ihrer Herstellung und deren Verwendung | |
| DE2504045A1 (de) | 16,17 dihydro-apovincaminsaeureester, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel | |
| EP0003298B1 (de) | 4-Hydroxy-2-benzimidazolin-thion-Derivate, Verfahren zu deren Herstellung sowie diese Verbindungen enthaltende Arzneimittel | |
| DE2723051B2 (de) | N^AcyO-p-amino-N'-Oi-decyl- und n-tridecyO-benzamide sowie diese enthaltende Arzneimittel | |
| DE2535599C2 (de) | Substituierte Zimtsäureamide, Verfahren zu ihrer Herstellung und pharmazeutische Zubereitungen, welche diese Verbindungen enthalten | |
| WO1979000426A1 (fr) | Diamine cyclique n, n'-disubstituee et procede pour sa preparation | |
| AT344151B (de) | Verfahren zur herstellung von neuen naphthalinderivaten | |
| DE2432269A1 (de) | Basisch substituierte derivate des 4-hydroxybenzimidazols und verfahren zu ihrer herstellung | |
| EP0045911B1 (de) | Neue Aminopropanol-Derivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| DE2939914C2 (de) | N-(1-Methyl-2-pyrrolidinylmethyl)-2,3-dimethoxy-5-methylsulfamoylbenzamid-Derivate, Verfahren zu ihrer Herstellung und Arzneimittel | |
| EP0029992B1 (de) | Neue Aminopropanolderivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| DE2923817B1 (de) | (3-Alkylamino-2-hydroxypropoxy)-furan-2-carbonsaeureanilide und deren physiologisch vertraegliche Saeureadditionssalze und Verfahren zu deren Herstellung sowie Arzneimittel mit einem Gehalt dieser Verbindungen | |
| AT375650B (de) | Verfahren zur herstellung von neuen 4-hydroxy-2 -benzimidazolinon-derivaten und von deren salzen, razematen und optisch aktiven formen | |
| EP0088986A2 (de) | Bicyclische Phenolether, Verfahren zu deren Herstellung sowie diese Verbindungen enthaltende Arzneimittel | |
| DE2801953A1 (de) | 4-hydroxy-2-benzimidazolinon-derivate, verfahren zu deren herstellung sowie diese verbindungen enthaltende arzneimittel | |
| DE3886125T2 (de) | Harnstoff-Derivate. | |
| DE2012667A1 (de) | Acyloxyalky!verbindungen, ihre Salze, Verfahren zu ihrer Herstellung und ihre Verwendung | |
| AT356101B (de) | Verfahren zur herstellung von neuen arylimino- imidazolidinderivaten und ihren salzen | |
| DE3150055A1 (de) | Di-fanresyl-verbindungen und verfahren zu deren herstellung |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| AK | Designated contracting states |
Designated state(s): BE CH DE FR GB LU NL SE |
|
| 17P | Request for examination filed | ||
| GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
| AK | Designated contracting states |
Designated state(s): BE CH DE FR GB LU NL SE |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: NL Effective date: 19810826 Ref country code: SE Effective date: 19810826 Ref country code: BE Effective date: 19810826 |
|
| REF | Corresponds to: |
Ref document number: 2860981 Country of ref document: DE Date of ref document: 19811119 |
|
| NLV1 | Nl: lapsed or annulled due to failure to fulfill the requirements of art. 29p and 29m of the patents act | ||
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19820831 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: LU Payment date: 19831228 Year of fee payment: 5 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: FR Payment date: 19840621 Year of fee payment: 7 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: CH Payment date: 19840820 Year of fee payment: 7 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: DE Payment date: 19840823 Year of fee payment: 7 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: CH Effective date: 19850831 |
|
| GBPC | Gb: european patent ceased through non-payment of renewal fee | ||
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: FR Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19860430 |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: PL |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: DE Effective date: 19860501 |
|
| REG | Reference to a national code |
Ref country code: FR Ref legal event code: ST |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: GB Effective date: 19881117 |
|
| PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |