Synthesis and SAR of 6-substituted purine derivatives as novel selective positive inotropes.

A series of purine derivatives was prepared and examined for selective inotropic activity in vitro and in vivo. Thioether-linked derivatives were superior to their oxygen and nitrogen isosteres. Substitution of electron-withdrawing groups on the benzhydryl moiety of these agents increased potency.

Synthesis of (aryloxy)alkylamines. 1. Novel antisecretory agents with H+K+-ATPase inhibitory activity.

A series of heterocyclic (aryloxy)alkylamines of structures II and III were prepared and found to possess gastric antisecretory activity. Of the variety of substituted thiazoles, benzoxazoles, and benzothiazoles prepared, thiazole 18, benzoxazole 32, and benzothiazole 47 exhibited gastric antisecretory potency comparable to that of ranitidine in vivo in the pylorous ligated rat model. In an isolated rabbit parietal system, the series of thiazoles, benzoxazoles, and benzothiazoles also demonstrated similar potency to that of ranitidine toward the inhibition of both histamine-stimulated and dcAMP-stimulated uptake of amino[14C]pyrine.

Antihypertensive pyrrolo[1,2-c]quinazolines and pyrrolo[1,2-c]quinazolinones.

The synthesis of a variety of pyrrolo[1,2-c]quinazolines and pyrrolo[1,2-c]quinazolinones is described. Several of these compounds have exhibited antihypertensive properties in the spontaneously hypertensive rat (SHR). Structure-activity comparisons have indicated that optimal activity is obtained in both the 2-carbethoxydihydroquinazoline series (C) and 2-carbethoxyquinazolinone series (D) when there is either a carbethoxy or cyanoethyl group at position 6 and no substitution in the benzene ring, while optimal activity is obtained in the 2-methyl-quinazolinone series (D) when both position 6 and the benzene ring are unsubstituted.