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Synthesis, Toxicological, Pharmacological, and Bronchodilating Activity in vitro of some Xanthineacetic Acid Derivatives
Author(s) -
Peikov Plamen,
Danchev Nikolai,
Zlatkov Alexander,
Ivanov Dimiter,
Belcheva Nadya
Publication year - 1995
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19953280709
Subject(s) - aminophylline , theophylline , chemistry , acute toxicity , theobromine , acetic acid , in vitro , acetylcholine , purine , pharmacology , biological activity , bronchodilator , toxicity , organic chemistry , biochemistry , enzyme , asthma , medicine
The possibility of the preparation of some ester derivatives of dimethylxanthines from 1‐theobromine‐ and 7‐theophylline acetic acids and 7‐(2‐hydroxyethyl)‐theophylline by DCC/DMAP‐mediated esterification under mild conditions was studied. The structures of the compounds synthesized and by products isolated were demonstrated by microanalyses, UV‐, IR‐, and 1 H NMR data. Acute toxicity assessment of the compounds on mice showed that compounds 4, 5, 6 , and 7 are less toxic than aminophylline. A pharmacological study of the in vitro broncholytic effect (IC 50 and pD 2 values) of the derivatives and aminophylline showed that the new compound 4 (1,2,3,6‐tetrahydro‐1,3‐dimethyl‐2,6‐dioxo‐7 H ‐purine‐7‐acetic acid 2‐(1,2,3,6‐tetrahydro‐1,3‐dimethyl‐2,6‐dioxo‐7 H ‐purine‐7‐yl)ethyl ester) has a strong bronchodilating effect on serotonine‐ and acetylcholine‐induced spasm in guinea pig trachea. The same compound does not influence barbiturate — induced hypnosis and locomotor activity, unlike to the effect of the aminophylline, used as a reference substance.