New 1,4-dihydropyridine derivatives combining calcium antagonism and .alpha.-adrenolytic properties

Abstract

A series of twelve 1,4-dihydropyridine derivatives incorporating an alpha-adrenergic moiety in one of the ester chains was synthesized. The compounds were evaluated for their calcium antagonist activities by the inhibition of [3H]nitrendipine binding and, in vitro, on pig coronary artery. Their alpha 1- and alpha 2-adrenolytic effects were assessed from their inhibition of [3H]prazosin and [3H]yohimbine binding and, in vitro, on rat aorta and guinea pig vas deferens. Compounds 6 and 9-11 displayed strong calcium antagonist activities, identical with that of nicardipine. The moderate alpha-adrenolytic properties observed were attributed to the presence of alpha-adrenergic moieties. The four chiral derivatives 6a (R,R), 6b (S,S), 6c (S,R), and 6d (R,S) with an N-methyl-N-(benzodioxanylmethyl)amino group on the ester chain were prepared and tested as done previously. Some structure-activity relationships are discussed.

1,4‐Dihydropyridines: Effects of Chirality and Conformation on the Calcium Antagonist and Calcium Agonist Activities

“…30 (1991) 1559-1578 essential to the pharmacological activity of the compounds, as is shown by 74 and 81. The pharmacological activity of 81, with the ester group in axial position, is weaker by two orders of magnitude than that of 74 …”

Hierarchical K/LTL zeolites: Synthesis by alkali treatment, characterization and catalytic performance in Knoevenagel condensation reaction

“…23 Knoevenagel condensation of aldehyde or ketone with active 24 methylene group compounds to form bulky unsaturated products 25 (Scheme 1) is one of the most important base catalyzed reactions 26 involving C-C bond formation and plays a vital role in the synthesis 27 of fine chemical [3][4][5] and employed as a probe reaction for the 28 characterization of the basic catalysts [6,7]. The homogeneous 29 Knoevenagel condensation reaction is catalyzed by using various 30 liquid bases such as piperidine, amines, ammonia, and ammonium 31 salts [8].…”

Effects of the Nitridation of Y and USY Zeolites on their Catalytic Activity for the Base Catalyzed Knoevenagel Condensation

“…Finally, the Knoevenagel condensation reaction between benzaldehyde and malononitrile was performed to evaluate the impact of the nitridation on the basicity. The Knoevenagel condensation is one of the reactions used for carbon-carbon bond formation and is often used for the commercial preparation of fine chemistry intermediates [17][18][19]. This reaction, which is a key step in the commercial production of antimalarial drug lumefantrine [19], is also largely employed as probe reaction for the characterization of catalyst basicity [18].…”