Cyclic guanidines. 14. Imidazo[1,2-a]thienopyrimidin-2-one derivatives as blood platelet aggregation inhibitors

Abstract

A series of novel 1,2,3,5-tetrahydroimidazo[1,2-a]thieno[2,3-d]-, -[3,2,-d]-, and -[3,4-d]pyrimidin-2-one derivatives has been prepared and tested for the activity of inhibiting platelet aggregation in rats in vitro and ex vivo. These compounds were synthesized through the following reactions: sodium borohydride reduction of 2,4-dichlorothienopyrimidines, followed by ethoxycarbonylmethylation and successive amination. Most of the compounds were found to be potent inhibitors of blood and platelet aggregation. Structure-activity relationships have indicated the essential contribution of the lactam structure and lipophilic substituents on the thiophene ring to the effective interaction of the compounds with a receptor site on the platelet. Among the compounds studied, 1,2,3,5,6,7,8,9-octahydro-[1]benzothieno[2,3-d]imidazo[1,2-a]pyrimidin-2-one (9m) exhibited the most favorable activity.

Condensed isoquinolines 29. Oxidation reactions of 5-aryl-7,12-dihydroisoquino[2,3-a]quinazolinium salts

“…However, by contrast to 5-oxoisoquino [2,3-a]quinazolines, the properties of the latter were not studied. The already existing data for the biological activity of isoquinoquinazolines [5,6] and 4-arylquinazolines condensed along the a edge [7][8][9] points to the potential of such an investigation.…”

Die Synthese von 2,3,4,5‐1H‐Tetrahydroimidazo[2,1‐b]chinazolin‐2,5‐dionen und analogen 2,3,4,5‐1H‐Tetrahydroimidazo[1,2‐a]thieno[2,3‐d] (bzw. [3,2‐d])‐pyrimidin‐2,5‐dionen

“…Imidazochinazolinone der allgemeinen Struktur 1 [ 1-51 und die analogen Imidazothienopyrimidindione 2 [6] [7] besitzen ein breites biologisches Wirkungsspektrum. So wirken sie auf den Kreislauf, als Lipidsenker, als Magensaftsekretionshemmer und besonders als Blutplattchenaggregationshemmer.…”

Guanidines from ‘toxic substances’ to compounds with multiple biological applications – Detailed outlook on synthetic procedures employed for the synthesis of guanidines

“…The reduction of steady-state currents in these axons was also voltage-dependent, with increasing block observed with increasing step depolarization. [196] [197] 81…”