Synthesis and pharmacological studies some 2–hydroxy haloalkylamines as H2 antagonist
Synthesis and pharmacological studies some 2–hydroxy haloalkylamines as H2 antagonist
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Date
2015-04-01
Authors
ElHassan, Amna
Journal Title
Journal ISSN
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Publisher
UOFK
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.
Description
Keywords
pharmacological studies,hydroxy haloalkylamines as H2