Synthesis and Positive Inotropic Evaluation of 2‐(4‐(4‐Substituted benzyloxy)‐3‐methoxybenzyl)‐1,4‐diazepan‐1‐yl)‐N‐(4,5‐dihydro‐1‐methyl[1,2,4]triazolo[4,3‐a]quinolin‐7‐yl)‐acetamides

Abstract

In an attempt to search for more potent positive inotropic agents, a series of 2-(4-(4-substituted benzyloxy)-3-methoxybenzyl)-1,4-diazepan-1-yl)-N-(4,5-dihydro-1-methyl[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamides was synthesized and their positive inotropic activities were evaluated by measuring left atrium stroke volume on isolated rabbit-heart preparations. Several compounds showed favorable activity compared with the standard drug Milrinone among which 2-(4-(4-(2-chlorobenzyloxy)-3-methoxybenzyl)-1,4-diazepan-1-yl)-N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamide 6e was found to have the most desirable potency with the 6.79 +/- 0.18% increased stroke volume (Milrinone: 1.67 +/- 0.64%) at a concentration of 1 x 10(-5) M in our in-vitro study. The chronotropic effects of those compounds having inotropic effects were also evaluated in this work.

Design, synthesis, and negative inotropic evaluation of 4‐phenyl‐1H‐1,2,4‐triazol‐5(4H)‐one derivatives containing triazole or piperazine moieties

“…Metoprolol was used as reference drug as negative inotropic drug clinically used for the treatment of congestive heart failure. The tested left atrium was perfused with N ‐2‐hydroxyethyl piperazine‐ N ‐2‐ethanesulfonic acid (HEPES) buffer solution use a peristaltic pump (1.25 mL/min) at 34 °C . The constituent of the buffer was as follows (in mmol): 4.7 KCl, 118 NaCl, 1.2 MgCl 2 , 2.5 CaCl 2 , 25 NaHCO 3 , 10.0 glucose, 10.0 HEPES (adjusted to pH 7.4 with 1 mol NaOH), and 0.1% bovine serum albumin (BSA).…”

Synthesis and in‐vitro inotropic evaluation of 2‐(4‐substitutedbenzyl‐1,4‐diazepan‐1‐yl)‐N‐(4,5‐dihydro‐1‐phenyl‐[1,2,4]triazolo[4,3‐a]quinolin‐7‐yl)acetamides

“…At the outset of our studies, a series of 2-(4-(4-substitutedbenzyloxy)-3-methoxybenzyl)-1,4-diazepan-1-yl)-N-(4,5-dihydro-1-methyl [1,2,4]triazolo [4,3-a]quinolin-7-yl)acetamides was synthesized and tested for their biological activity. Among these compounds, 1 showed significant inotropic activity (four-times more potent than milrinone at 1 Â 10 À5 M) [9]. The result seems to indicate that incorporating triazole ring to the 1,2-position of 3,4-dihydro-2(1H)-quinolinone is beneficial to enhance the activity, and some derivatives bearing phenyl group at 1-position of the triazole ring also showed good activity [10].…”