Novel phenoxyalkylamine derivatives. III. Quantitative structure-activity relationships of Ca2+-antagonistic .ALPHA.-alkyl-.ALPHA.-((phenoxypropylamino)propyl)-3,4,5-trimethoxybenzeneacetonitrile derivatives.
- 1 January 1988
- journal article
- research article
- Published by Pharmaceutical Society of Japan in CHEMICAL & PHARMACEUTICAL BULLETIN
- Vol. 36 (2) , 776-783
- https://doi.org/10.1248/cpb.36.776
Abstract
The effects of structural modifications of .alpha.-alkyl-.alpha.-[(phenoxypropylamino)propyl]-3,4,5-trimethoxybenzeneacetonitrile derivatives on their Ca2+-antagonistic activity were analyzed quantitatively by means of the Hansch-Fujita method. The effect of the alkyl substituent at the .alpha.-quaternary carbon atom was rationalized by a parabolic function of either steric parameter MR or .DELTA.B5, whrere the optimal value is MR = 1.83 or .DELTA.B5 = 3.04. For substituents on the benzene ring (B ring) at the phenoxy moiety, an electron-releasing substituent with about .pi. = 0 seemed to be most favorable to the activity. The correlations with the local steric and hydrophogic parameters, .DELTA.B5para and .pi.para, of the para substituent of the B ring showed that a substituent with small width and high hydrophobicity is favorable in enhancing activity, leading to the conclusion that hydrogen is the most preferable para substituent. The most effective compound (24) examined in this study has an m-OMe group on the B ring and an iso-Pr group at the quaternary carbon atom. This observation was in agreement with the present analyses.This publication has 1 reference indexed in Scilit:
- SIGMA VALUES FROM REACTIVITIES1The Journal of Physical Chemistry, 1960