Synthesis and pharmacological studies some 2–hydroxy haloalkylamines as H2 antagonist

Abstract

The preparation of the 2–(N,N–dibenzylamino)–1–P–haloaryl–1– hydroxy ethane was carried out according tothe synthetic routes shown in the general scheme of work. The methods used are known in the literature. The acetophenones (1) were first brominated to the phenacyl bromides (2) using molecular bromine in dry diethyl ether at room temperature. The acidic conditions necessary for the reactions were attained by the small amount of HBr usually present in the bromine liquid. However, depending on the reactivity of the acetophenone, the use of a catalyst is sometimes recommended. This has actually been the case in the preparation of some of the phenacyl bromides in thiswork by using anhydrous AlCl3. The phenacyl bromides using Na BH4. This reagent was chosen because of its specificity in reducing Keto groups and because of the mild conditions usually used with it. The reductions were carried out in aqueous methanol suspension at room temperature and sometimes at 50°C. In all the reactions the phenacyl bromides and the bromohydrins indicated sufficient purity to justify direct subsequent use. The bromohydrins were condensed with dibenzylamine (4) in dry benzene to give the amino alcohol (5). This is SN2reaction and the choice of dry benzene has been the result of several trials of solvents of varying degrees of polarity. The use of heatwas found essential for the increase of the yield of the amino alcohols. The condensation reactions were carriedout in refluxing benzene. Due to the high boiling point of dibenzylamine and its similar solubility properties to those of the amino alcohols, the latter were isolated from the reaction mixtures by preparative TLC. The amino alcohols were obtained as yellow liquids. The amino alcohols were used in the pharmacological screenings as their hyarochloride salts. These were obtained by adding calculated amounts of ethanolic HCl to the solutions of the amino alcohols free bases in absolute ethanol and precipitating the hydrochloride salts with diethyl ether. Two 2–hydroxyhaloalkylamine have been prepared according to well– documented synthesis routes in literature. The two compounds thus obtained were investigated pharmacologically to show their anti–ulcer activity. Both studied compounds blocked the relaxing effect of histamine in rat uterus. Both studied compounds antagonized histamine effect completely in guinea pig heart and brought the heart to its normal. In rat stomach, both compounds reduce ulcer lesions. All the above actions of the studied were found to be through H2 receptors blocking activity. In addition the two compounds showed H1 antihistaminic activity as they blocked histamine effect in guinea pig ileum.