New series of cardioselective adrenergic .beta.-receptor blocking compounds. 1-(2-Acyl-4-acylaminophenoxy)-3-isopropylaminopropan-2-ols

Abstract

A series of 1-(2-acyl-4-acylaminophenoxy)-3-isopropylaminopropan-2-ols has been synthesized and examined for beta-receptor blocking and antiarrhythmic activity. Several of these compounds are more than 20 times as active in blocking cardiac beta-receptors than vascular beta-receptors when given intravenously to anesthetized cats. The activities have been correlated quantitatively with partition and steric substitution constants. The observed relationships are consistent with a tentative proposal that the vascular receptor is situated in a more lipophilic environment than the cardiac receptor so that there is a differential transport effect between the two types of receptor.

A Comparison of the Bronchoconstrictor and Β‐adrenoceptor Blocking Activity of Propranolol and Acebutolol

“…Comparison of the 3rd and 4th columns of Table 1 shows that acebutolol and M&B 19421 were more active antagonists at /31-than #2-adrenoceptors and that M&B 16942A was equally effective on both types of receptor. This confirms the findings of Basil et al (1976). The present results also agree with those of Maxwell & Collins (1974); in both studies acebutolol was more selective for the cardiac #l,-receptors than the bronchial 32-receptors.…”

“…The following drugs were used: isoprenaline sulphate (Burroughs Wellcome); (±+propranolol (ICI); acebutolol and two of its analogues, M&B 16942A and 19421 (May and Baker). Details of the analogues of acebutolol are given in Table 1 of the paper by Basil, Clark, Coffee, Jordan, Loveless, Pain & Wooldridge (1976). The compounds chosen for the present experiments were Compound 1, M&B 16942A…”

Use of enantioselective liquid chromatography for preparation of pure atenolol enantiomers

“…The usual synthesis of racemic 3-aryloxy-1-isopropylamino-2-propanol proceeds via the aminolysis of respective glycidylaryl ethers with isopropylamine [12,13]. Atenolol (1), a widely known antihypertensive drug, was usually prepared [14] by the standard procedure given in Scheme 1.…”

Biocatalytic Approach for the Synthesis of Enantiopure Acebutolol as a β1‐Selective Blocker

“…Acebutolol is used in the treatment of high blood pressure, abnormal heart rhythms, and sometimes chest pain . Similar to other β ‐blockers, acebutolol is used as a racemic mixture, despite the fact that its β ‐blocking activity is attributed to the S ‐enantiomer and its major metabolite S ‐diacetolol .…”

“…9,10 Acebutolol is used in the treatment of high blood pressure, abnormal heart rhythms, and sometimes chest pain. [11][12][13][14][15][16][17] Similar to other β-blockers, acebutolol is used as a racemic mixture, despite the fact that its β-blocking activity is attributed to the S-enantiomer and its major metabolite S-diacetolol. 18 Moreover, it has been reported that both the enantiomers of adrenergic β-receptor blockers are not only different from the pharmacodynamic point of view but their pharmacokinetic properties are also very different.…”