Hiroyuki Obase

Non-prostanoid thromboxane A2 receptor antagonists with a dibenzoxepin ring system. 1

A series of 11-[[2-[(arylsulfonyl)amino]ethyl]thio]-6,11- dihydrodibenz[b,e]oxepin-2-carboxylic acids and related derivatives were synthesized. The compounds were tested for their antagonizing effects on guinea pig platelet TXA2/PGH2 receptors. Structure-activity relationships are discussed. (+/-)-11-[[2-[(Styrylsulfonyl)amino]ethyl]-thio]-6,11- dihydrodibenz[b,e]oxepin-2-carboxylic acid (41) and (+/-)-11-[[2-[(phenylsulfonyl)amino]ethyl]thio]-6,11- dihydrodibenz[b,e]thiepin-2-carboxylic acid (4af) were the most promising compounds with K(i) values of 6.5 +/- 0.29 and 3.7 +/- 0.31 nM, respectively, for the TXA2/PGH2 receptor. These compounds also significantly inhibited U-46619-induced guinea pig platelet aggregation ex vivo (10 mg/kg po). Compound 41 was resolved into its optically active form. The (-)-isomer was 60-fold more potent than the (+)-isomer in the TXA2/PGH2 receptor binding assay. Some compounds tested in this study showed both TXA2/PGH2 receptor antagonizing and TXA2 synthase inhibitory effects.

Synthesis and in vitro gastrointestinal motility enhancing activity of 3-aryl-2-imidazolidinylidene propanedinitrile derivatives

Abstract Novel N -3-arylated imidazolidinylidene propanedinitrile derivatives 2a–f were prepared by a new intramolecular cyclization method and their AChE inhibitory activity and in vitro gastrointestinal motility enhancing activity were evaluated. All compounds except 2f were found to be potent in both activities.