A. A. Kimenis

Synthesis and cardiovascular activity of substituted 3-cyano-3,4-dihydropyridine-2-thiones and 3-cyanopyridine-2-thiones

H H Ia-g , Ila-f I l la-f Ia-g:R i = H, R s ---Phi lla-d, I:R i = = C O O E r , R ~ = Me; IIe R 1 = COObte, R s = Me; Ia:R = H; IbfR = OCHFs-o; ~:R = F-o; Id~R = F@; I~:R = NO~.m; I~R = N@9~; I~:R = Br-~ I Ia :R~ H; ~b:R = NO~.m; IIq.R = NO~-p; IId, e,R = =CI-P; IIe:R = OMe-P; I l la ,b;R1 = Me; IIIr l = p h ; IIIa:R=Me; I I I b , c : R = =Ph; I I Id :R= C~H4OCHF2-o; IIIe:R = =C6HINO2-~ III~R=C6H4CI-p.

Pharmacological effects and mechanism of action for preparations of the 1,4-dihydropyridine series on the cardiovascular system (review)

By their mechanism of action, compounds of the 1,4-dihydropyridine series may be considered as antagonists of calcium ions [36]. This class of medicinal compounds has found widespread application in recent years for the treatment of such diseases as arterial hypertension, arrhythmia, and ischemic heart disease [35], Antagonists of calcium ions have spasmolytic activity towards both coronary and cerebral vessels. They also act on peripheral vessels, as a result of which the systemic arterial pressure is lowered [45].

Effect of 1,4-dihydropyridine derivatives on the cardiovascular system

Almost no vasoselectivity was exhibited by the first cardiovascular preparations of the 1,4-dihydropyridine series. Alterations in their structure resulted in the synthesis of calcium channel blockers such as intrendipine [I], nimodipine [2], and nicardipine [3] which primarily act upon peripheral vessels. Recent searches for compounds exhibiting pronounced selectivity resulted in the synthesis of 1,4-dihydropyridines which contain halide methyl groups in position 2 [4-7]. Some of these compounds exhibit a high degree of selectivity [6] or more extended activity [7]. There are data that show that halide derivatives of intrendipine exhibit less negative inotropic action, although in some cases their vasodilatory action is even greater than in nitrendipine [8].

Synthesis and pharmacological activity of analogs of the hypotensive drug Foridon

The synthesized 1,4-dihydropyridines are colorless crystalline substances: Compounds le-g have a yellowish color. The UV spectra exhibit two absorption maxima, at 240 and 350-370 ran. The introduction of an amide group into position 5 (Id) induced a hypsochromic shift of the longwave absorption maximum (A ~ 15 nm) in comparison to the complex ester group. Replacement of the oxygen atom by a sulfur atom in the aryl substituent (le-g) results in a certain bathochromic shift of the longwave maximum which diminishes as the lengths of the alkyl groups in positions 3 and 5 increaser

Study of the biotransformation of 1,4-dihydropyridines in experiments in vitro

In this work we studied processes of biotransformation of two preparations of the 1,4-dihydropyridine series: 2,6-dimethyl-3,5-diethoxycarbonyl-l,4-dihydropyridine (i, diludine) and 2,6-dimethy~-3,5-dimeth~xycarb~ny~-4-(~-dif~u~r~meth~xypheny~)-l,4-dihydr~pyridine (Ii, foridone), synthesized at the Institute of Organic Synthesis, Academy of Sciences of the Latvian SSR. One of them, antioxidant I, is a stabilizer of vitamin A [I, 4]; the other, II, possesses pronounced hypotensive activity [6, 13]. Earlier, in experiments in vivo we established the structure of three metabolites of [:~C]i and five metabolites of [:~C]il, which constitutes 97and 77% of the radioactive products excreted with the urine, respectively [3, i!].

Metabolism of diludine in experimental animals

A study of the biotransformation of diludine is valuable for the complete pharmacological and toxicological evaluation of the drug. The authors present the results of a study of the qualitative and quantitative composition of its metabolites in rats and rabbits. /sup 14/C-labeled I was produced from (1,3-/sup 14/C)acetoacetic ester with an 80% yield. It is established that I is virtually entirely metabolized in the bodies of the experimental animals.

4-substituted 2,6-dimethyl-3,5-di-β-alkoxyethoxycarbonyl-1,4-dihydropyridines

N-Unsubstituted 2,6-dimethyl-l,4-dihydropyridines containing B-alkoxyethoxycarbonyl groups in positions 3 and 5 and various substituents both in position 4 (pyridyl-, phenyl-, and substituted phenyl groups) and in the ester group (S-ethoxyethyl and S-butoxyethyl esters) have been prepared and studied in this work. N-Methyl derivatives of 1,4-dihydropyridines of this type have also been synthesized. The N-unsubstituted derivatives of 1,4-dihydropyridine (I-VIII) were prepared under the Hantzsch conditions for the synthesis of dihydropyridines from 1 mole of the appropriate aldehyde, 2 moles of the Balkoxyethyl ester of acetoacetic acid, and 1.5 moles of ammonia in alcohol solution (Table i). The carrying out of the reaction requires rather prolonged boiling (6-10 h). The low yields of certain of these compounds are explained by their high solubility in the reaction medium which hinders their isolation.