Patent Evaluation: Quinazolinones and pyridopyrimidinones as angiotensin II antagonists

Summary

Novelty: Novel quinazolines and pyridopyrimidinones are claimed as angiotensin II antagonists useful for the treatment of hypertension. In additional representative compounds from this patent are said to have potential utility in treating certain CNS disorders and congestive heart failure.

Biology: The compounds of this patent were evaluated in several tissues for angiotensin II receptor binding affinity including rabbit aortae membrane, bovine adrenal cortex, and rat brain membrane. Representative compounds were found to exhibit balanced AT₁/AT₂ activity of at least 10 μM IC₅₀. However, specific binding data for representative compounds are not provided. Useful CNS activities of these compounds can be demonstrated in a rat passive avoidance assay (cognitive assay), in a rat conditioned emotional response assay (anxiolytic assay), in a mouse tail suspension test (depression assay), and in an apomorphine-induced stereotype model (schizophrenia assay).

Chemistry: The compounds of this patent were synthesized starting from 5-chloro-2-ni-trobenzonitrile as described in six schemes with fifty-nine compounds being specifically claimed.