A. G. Mikhailovskii, A. Dolzhenko, B. Y. Syropyatov
Jun 1, 2002
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0
Influential Citations
6
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Quality indicators
Journal
Pharmaceutical Chemistry Journal
Abstract
Previously we studied a series of isoquinoline derivatives exhibiting antiaggregant effect with respect to thrombocytes [1 – 5] and possessing hypotensive properties [6 – 8]. At the same time, derivatives of 1-chloromethylisoquinoline [9 – 11] are still not characterized with respect to pharmacological activity. To our knowledge, the properties of 1-methylisoquinoline esters were also never reported in the literature. When the ester residue represents an aromatic or benzyl fragment, such molecules differ from papaverine by the presence of an oxygen bridge. In this context, it was of interest to compare the pharmacological properties of these esters and papaverine. The aim of our study was to determine the effect of 1-chloromethyl-3,4-dihydroisoquinolines (II) and benzo[f]isoquinoline esters (IV) on the thrombocyte aggregation and arterial pressure in experimental animals. The latter compounds were selected as objects for the investigation because previously we observed a pronounced hypotensive activity in benzo[f]isoquinoline derivatives [7, 8]. The series of chloromethylisoquinolines IIa – IIe was synthesized by means of the interaction of carbinols Ia – Ie with chloroacetonitrile under the Ritter cyclocondensation conditions [1 – 3, 7, 8]. Esters IVa – IVf were obtained via reactions of compound III, obtained previously by the same method [7], with alcohols and phenols under conditions of phase-transfer catalysis [12]. In particular, the interaction of III with benzyl alcohol to yield compound IVa (R = PhCH2) [12] proceeds in a KOH/benzene system and is catalyzed by 18-crown-6. The interaction between III and phenols, proceeding in a 50 % NaOH/CH2Cl2 system and catalyzed by tetrabutylammonium hydrosulfate, led to phenyl esters IVb – IVf. Data on the yields, structures (R–R), and properties of the synthesized compound are presented in Tables 1 – 3.