Synthesis and cardiotonic evaluation of R-sulfonyl derivatives of azaheterocycles.
A series of alpha-sulfonyl-2-(3-chloro)hetarylacetonitriles was prepared by the interaction of dichlorodiazines and R-sulfonylacetonitriles. Reaction of nucleophilic substitution of chlorine by different N-H-azoles has been studied. The compounds obtained showed 3 types of activity on cardiac papillary muscles: 1. a biphasic activity with increase in cardiac contractility at low concentration and inhibition in high concentration (1, 2, 4, 12-15), 2. a monophasic inhibitory activity (3, 5, 8-10), 3. non-active compounds (6, 7, 11). The preliminary SAR studies indicate the importance of chlorine atom at position 3 in diazine nucleus and of alkyl substituents in benzimidazole moiety for positive inotropic effects.
Grinevich
A I
AI
Medical Institute, Kiev, Ukraine.
Litvinenko
S V
SV
D000097:Acetonitriles / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000494:pharmacology
D000097:Acetonitriles; D001372:Aza Compounds; D013450:Sulfones