2, 2'-Dithiodibenzamides as Inhibitors of Blood Platelet Aggregation

• Published in: Chemical & pharmaceutical bulletin Vol. 33; no. 3; pp. 1214 - 1220
• Main Authors: YAMADA, KOJI, HASHIMOTO, TAMOTSU, SHUTO, KATSUICHI, NIINO, HIDEKI, KUBO, KAZUHIRO, NAKAMIZO, NOBUHIRO, MURAYAMA, YO, ONO, TAKESHI, NAKAMIZO, AKIO
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.01.1985; 公益社団法人日本薬学会; Maruzen; Japan Science and Technology Agency
• Subjects: Adenosine Diphosphate - pharmacology; Amides - chemical synthesis; Animals; Chemistry; Collagen - pharmacology; dithiodibenzamide; ex vivo aggregometry; Exact sciences and technology; in vitro aggregometry; Indicators and Reagents; Noncondensed benzenic compounds; Organic chemistry; Platelet Aggregation - drug effects; platelet aggregation inhibitor; Preparations and properties; pulmonary thrombosis; Rabbits; Structure-Activity Relationship; Thioamides - chemical synthesis; Thioamides - pharmacology; Organic disulfide; Platelet; Structure activity relation; Carboxamide; Benzenic compound; Biological activity; Antiplatelet agent
• ISSN: 0009-2363; 1347-5223; 1347-5223
• DOI: 10.1248/cpb.33.1214

New and known analogues of 2, 2'-dithiodibenzamide were synthesized and tested for various pharmacological actions. This series of compounds was found to inhibit collagen-and adenosine 5'-diphosphate-induced aggregations of blood platelets. 2, 2'-Dithiobis (N-(2-hydroxypropyl) benzamide) (3, KF4939) was one of the most potent compounds in in vitro aggregometry studies. Compound 3 after oral administration also potently inhibited pulmonary thrombosis induced by arachidonic acid injection in mice and platelet aggregation ex vivo in rats. This compound may have clinical value as a new orally active inhibitor of platelet aggregation.