Patent Evaluation: Substituted aminopyrimidines as angiotensin II antagonists in treatment of hypertension and heart failure

Abstract

Novelty: Novel substituted aminopyrimidines, having angiotensin I1 antagonist activity, are disclosed. Compounds of the claim are stated to have potential utility for treatment of hypertension and congestive heart failure. It is further proposed that they are lipid lowering agents and so have additional utility for treatment of hyperlipidaemia and hypercholesterolaemia as well as treatment of restenosis following angioplasty.

Biology: The compounds of this patent were evaluated for angiotensin I1 receptor binding affinity in rat adrenal tissues. 23 representative compounds exhibited binding affinities from 500-2.5nM. It is stated that the compounds of the present invention showed antihypertensive activity in an A-II infused rat model. One example (47) lowered blood pressure by 57% four hours post administration (3mgkg id).

Chemistry: The compounds of this patent were synthesized starting from 5-[(4-aminomethyl)[1,l -biphen-2-y1]]- 1H-tetrazole hydrochloride as described in one scheme with 23 compounds being specifically claimed.