.beta.-Adrenergic blocking agents. 19. 1-Phenyl-2-[[(substituted-amido)alkyl]amino]ethanols

Abstract

The synthesis of a series of derivatives of 1-phenyl-2-[[(substituted amido)alkyl]amino]ethanols is described. The compounds were investigated for beta-adrenoceptor blocking properties, and many showed a surprising degree of potency and beta 1-cardioselectivity when tested in vivo in anesthetized cats. The structure-activity relationships shown by this series of compounds are discussed and related to known beta-adrenergic blocking agents.

Synthesis and evaluation of 1- and 2-substituted fentanyl analogs for opioid activity

“…The IC50 of fentanyl in the MVD was 9.45 ± 4.05 X 10™9 M (n = 11), while that for morphine was 1.94 ± 0.34 X 10-( = 3). Compound 13, which differs from fentanyl (1) only in having an aminocarbonyl group at the 2-position, was 110 and 450 times less potent than fentanyl in the GPI and MVD, respectively. None of the other fentanyl derivatives at a concentration of 1 X 10"6 M (9) .…”

Quantitative structure-activity relationships employing independent quantum chemical indexes

“…1972, 15, 1066. (8) Anderson, T. The results of this study indicated that the number of essential factors is less than the number of primary indices and that the first component was the most important one in determining pharmacological activity. Methods…”

“…The transformation coefficients were calculated by using principal component analysis. 8 Principal component analysis was used several times in QSAR studies. The investigations involved geometric descriptor indices, substituent constants,9-13 pharmaco- (1) Schnaare, R. S. Drug Des.…”

“…The coefficients c¡j forming matrix c, were obtained by using principal component analysis. 8 The sum of the sample variances of the transformed indices xj is m and is referred to as total sample variance. The sum of the variances of variables X¡ is also m. While the variance of each variable x¡ is 1, the variances of variables X¡ are different.…”