Novel Phenoxyalkylamine Derivatives. I. : Synthesis and Pharmacological Activities of α-Isopropyl-α-[(phenoxyalkylamino)alkyl]-benzeneacetonitrile Derivatives

Abstract

Novel α-isopropyl-α-[(phenoxyalkylamino)alkyl]benzeneacetonitrile derivatives, the phenoxyalkylamino moiety of which was introduced in place of the phenethylamino moiety of verapamil (known to be an excellent Ca²⁺-antagonist), were synthesized and their pharmacological activities were evaluated. These compounds exhibited α-bloking activity along with Ca²⁺-antagonistic activity, and their activities were influenced by the substituent on the amino nitrogen atom and by the number of carbons between the nitrogen atom and the benzeneacetonitrile moiety (m) as well as that between it and the pheoxy moiety (n). Among these compounds, the N-methyl derivative (2h) where m=n=3, was found to possess a high Ca²⁺-antagonistic activity and the N-H derivative (2c) in which m=3 and n=2 possessed a high α-blocking activity.