Chegaev, Konstantin Lazzarato, Loretta Marcarino, Paolo Stilo, Antonella Di Fruttero, Roberta Vanthuyne, Nicolas Roussel, Christian Gasco, Alberto Synthesis of Some Novel Organic Nitrates and Comparative in Vitro Study of Their Vasodilator Profile Synthesis and structural characterization of the 4-phenylbutane-1,2-diyl dinitrate and of the <i>erythro</i> and <i>threo</i> diastereoisomers of 4-phenylbutane-1,2,3-triyl trinitrate as well as the HPLC chiral separation of the corresponding racemic mixtures are reported. Vasodilator activity of the single enantiomers of these products, of 4-phenylbutyl nitrate, and of the previously described phenylpropyl analogues were assessed on rat aorta strips precontracted with phenylephrine. The compounds were able to relax the contracted tissue in a concentration dependent manner. In the couples of antipodes, a complete lack of enantioselectivity was observed as far as the vasodilator potency is concerned. The concentration response curves of the products, with the exception of those of all the trinitrooxy substituted models, were rightward shifted in the presence of ALDH-2 inhibitors. Mono and dinitrates, but not trinitrates, displayed in vitro cross-tolerance with GTN. This new series of nitric acid esters is an interesting tool that can help to shed light on the unresolved puzzle of nitrate pharmacology. Selected members are worthy of additional study as potential drugs. enantioselectivity;phenylpropyl analogues;Novel Organic Nitrates;presence;ALDH;Mono;couple;compound;trinitrate;racemic mixtures;threo diastereoisomers;series;Vitro Study;phenylbutane;lack;Vasodilator ProfileSynthesis;antipodes;erythro;phenylbutyl;vasodilator potency;characterization;puzzle;phenylephrine;enantiomer;nitric acid esters;tool;GTN;rat aorta strips precontracted;exception;Comparative;inhibitor;nitrate pharmacology;concentration response curves;tissue;manner;dinitrate;Selected members;Vasodilator activity;HPLC chiral separation;trinitrooxy;model 2009-07-09
    https://acs.figshare.com/articles/journal_contribution/Synthesis_of_Some_Novel_Organic_Nitrates_and_Comparative_in_Vitro_Study_of_Their_Vasodilator_Profile/2844373
10.1021/jm9002236.s001