New thiazolopyrimidine derivatives, synthesis and structure-activity relationships

Article abstract of DOI:10.1016/0223-5234(92)90099-M

Twenty-six derivatives of 5- and 7-oxo or 5- and 7-aminothiazolo<3,2-a>pyrimidines were prepared and evaluated as positive inotropic, anti-inflammatory and antihypertensive agents both in vitro and in vivo.The structures of the 5- and 7-isomers have been confirmed unambiguously by IR, UV, 1H and 13C NMR and MS.The structure of 1a was confirmed by the synthesis of compound 1 whose structure had been previously established by X-ray analysis.The 5-aminothiazolo-pyrimidine-6-carbonitrile derivatives 5a and 5e exhibited potent inotropic activities. 5e was more potent thanthe classical reference amrinone.Three compounds 5e, 5i and 5j displayed moderate antihypertensive activities.The 4-chlorophenyl derivative 5d exhibited an anti-inflammatory activity 2-fold that of aspirin.This study has demonstrated that thiazolo<3,2-a>pyrimidine compounds have interesting biological potentialities, particularly as inotropic agents, a field which had never been explored so far for this series. thiazolo<3,2-a>pyrimidines / cardiotonic / inotropic / antihypertensive / anti-inflammatory activity