Synthesis and Antiarrhythmic Activity of 2, 2-Dialkyl-1'-(N-substituted aminoalkyl)-spiro-[chroman-4, 4'-imidazolidine]-2', 5'-diones

• Published in: Chemical & pharmaceutical bulletin Vol. 40; no. 7; pp. 1823 - 1827
• Main Authors: MATSUKURA, Masayuki, DAIKU, Yoshiharu, UEDA, Kouichirou, TANAKA, Satoru, IGARASHI, Toshiji, MINAMI, Norio
• Format: Journal Article
• Language: English
• Published: TOKYO The Pharmaceutical Society of Japan 01.07.1992; Pharmaceutical Soc Japan; Maruzen; Japan Science and Technology Agency
• Subjects: (-)-6-chloro-2, 2-dimethyl-1'-[3-(4-hydroxypiperidino)propyl]-spiro-[chroman-4, 4'-imidazolidine]-2', 5'-dione; 2, 2-dialkyl-1'-(N-substituted aminoalkyl)-spiro-[chroman-4, 4'-imidazolidine]-2', 5'-dione; acontitine-induced arrhythmia; Animals; Anti-Arrhythmia Agents - chemical synthesis; Anti-Arrhythmia Agents - pharmacology; Anti-Arrhythmia Agents - toxicity; antiarrhythmic activity; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; chloroform-induced arrhythmia; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Imidazoles - chemical synthesis; Imidazoles - pharmacology; Imidazoles - toxicity; Lethal Dose 50; Life Sciences & Biomedicine; Mice; Organic chemistry; Pharmacology & Pharmacy; Physical Sciences; Preparations and properties; Science & Technology; Spiro Compounds - chemical synthesis; Spiro Compounds - pharmacology; Spiro Compounds - toxicity; spirohydantoin; Structure-Activity Relationship; CHLOROFORM-INDUCED ARRHYTHMIA; ACONTITINE-INDUCED ARRHYTHMIA; ANTIARRHYTHMIC ACTIVITY; (-)-6-CHLORO-2,2-DIMETHYL-1'-[3-(4-HYDROXYPIPERIDINO)PROPYL]-SPIRO-[CHROMAN-4,4'-IMIDAZOLIDINE]-2',5'-DIONE; SPIROHYDANTOIN; 2,2-DIALKYL-1'-(N-SUBSTITUTED AMINOALKYL)-SPIRO-[CHROMAN-4,4'-IMIDAZOLIDINE]-2',5'-DIONE; Five membered ring; Nitrogen heterocycle; Lactam; Tertiary amine; Bicyclic compound; Ureas; Aromatic compound; Oxygen heterocycle; Biological activity; Antiarrhythmia agent; Spiran; Halogen Organic compounds
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.40.1823

A novel series of 2, 2-dialkyl-1'-(N-substituted aminoalkyl)-spiro-[chroman-4, 4'-imidazolidine]-2', 5'-diones was synthesized and evaluated for antiarrhythmic activity in chloroform- or/and aconitine-induced ventricular arrhythmia in mice. Among these compounds, (-)-6-chloro-2, 2-dimethyl-1'-[3-(4-hydroxypiperidino)propyl]-spiro-[chroman-4, 4'-imidazolidine]-2', 5'-dione was found to be more effective than reference agents and was selected for further development.