Compounds with positive inotropic activity, IV: Synthesis of N-methoxyquinolinium salts and their effects in heart muscles.
N-Methoxyquinolinium salts 3 are prepared as potential cardiotonic agents by alkylation of the corresponding N-oxides 2 synthesized by two different methods. 1. Oxidation of some quinoline derivatives 1 using 30% H2O2 or 3-chloroperbenzoic acid. 2. Nitration of the quinoline-N-oxides 2a, 2c, and 2m. Preparation of 2h and 2k requires subsequent nucleophilic ipso-substitution of the nitro group. The compounds 3 are tested for positive inotropic activity on isolated left atria and papillary muscles from guinea-pig. Structure activity relationships indicate that the effect depends on the N-methoxy group of the target compounds as well as on the presence of an electron-withdrawing substituent.
Bünz
C
C
Department of Pharmaceutical Chemistry, University of Kiel.
Heber
D
D
Ravens
U
U
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D011806:Quinolinium Compounds / Q000138:chemical synthesis* / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D002316:Cardiotonic Agents; D011806:Quinolinium Compounds