4-dihydropyridine Derivatives Research Articles

ChemInform Abstract: New 1,4‐Dihydropyridine Derivatives with Potent and Long‐Lasting Hypotensive Effect.

AbstractDie Kondensation der Ausgangsverbindungen (I)‐(III) miteinander führt zu einer Vielzahl neuer 1,4‐Dihydropyridine (IV), von denen viele blutdrucksenkend wirken.

O-105 - Calcium antagonistic effects of KW-3049, a new 1, 4-dihydropyridine derivative, in isolated canine coronary arteries

O-105 - Calcium antagonistic effects of KW-3049, a new 1, 4-dihydropyridine derivative, in isolated canine coronary arteries

New 1,4-dihydropyridine derivatives with potent and long-lasting hypotensive effect.

In a search for new 1, 4-dihydropyridine derivatives with a long-lasting effect on the cardiovascular system, a series of piperazinylalkyl esters (I) bearing a lipophilic substituent on the 4-nitrogen of the piperazine ring was synthesized and tested for hypotensive effect in spontaneously hypertensive rats (SHR). Compounds I, especially those having a diphenylmethyl moiety on the piperazine ring, showed extremely potent and long-lasting hypotensive properties. Analogues related to I were also prepared, and the structure-activity relationships are discussed.

ChemInform Abstract: SYNTHESIS AND REACTIONS OF HETEROCYCLIC DITHIOCARBAMATES

AbstractDie Aminopyridiniumsalze (I) reagieren mit Schwefelkohlenstoff zu den Salzen (II), die mit Dimethylsulfat in die Dithiocarbamate (III) übergehen.

Synthesis and reactions of heterocyclic dithiocarbamates.

(Alkylthio) thiocarbonylimino-1-methyl-1, 2-dihydropyridine derivatives (3a-e) were prepared by the reaction of 2-amino-1-methylpyridinium iodide (1a-c or d) with carbon disulfide in the presence of sodium hydride and subsequent methylation with dimethyl sulfate in good yields. Similarly, 1-methyl-4-(methylthio) thiocarbonyl-1, 4-dihydropyridine (3i), 1-methyl-2-(methylthio) thiocarbonyl-1, 2-dihydrothiazole (3g), and 1-methyl-2-(methylthio) thiocarbonyl-1, 2-dihydrobenzothiazole (3h) were synthesized by the reaction of the corresponding 2-imino- and 4-imino-N-methyl heterocyclic compounds with carbon disulfide. The reaction of 3a-e with dimethyl acetylenedicarboxylate afforded the 2- or 4-[1, 2-bis (methoxycarbonyl)-2-thioxoethylidene]-1, 2- or 1, 4-dihydropyridine derivatives (8a-d). The reaction of 3i with dimethyl acetylenedicarboxylate (2 mol) gave cyclobuta [b] azocine (9). The reaction of 3h with dimethyl acetylenedicarboxylate afforded 2, 3-dihydrobenzothiazole-2-spiro-2'-(2H-pyrrole) (10). 2-[N-bis (methylthio) methylene] amino-N-methylpyridinium and benzothiazolium iodide (11b, c), which were prepared by the methylation of 3a and h with methyl iodide, reacted with nucleophiles to yield the corresponding products substituted on one or two methylthio groups.

Streptonigrin and related compounds. IV. Syntheses of 4-(3,4-methylene-dioxyphenyl)- and 4-(3,4-dimethoxyphenyl)-3-cyano-5-ethoxycarbonyl-6-methyl-2-quinolylpyridine. (Studies on the synthesis of heterocyclic compounds. CXLIX)

Some of the polysubstituted 4-phenylpyridine derivatives show pharmacological activity and, therefore, synthesis was attempted for compounds having a structure similar to the 4-phenylpyridine skeleton present in the structure of streptonigrin. First, examinations were made for the synthesis of C-D rings in streptonigrin and synthesis was effected for 4-(3, 4-methylenedioxyphenyl)-3-cyano-5-ethoxycarbonyl-6-methyl-2-quinolylpyridine, which has a streptonigrin skeleton and a substituent that could be derived to its C ring. The methods used for these syntheses can be classifield into the following three : (1) Condensation of α-cyanocinnamide and ethyl 3-aminocrotonate, (2) Condensation of cyanoacetamide with the product of the Claisen-Schmidt reaction, and (3) the Hantzsch-type synthesis. 4-Phenylpyridine was obtained as the product using methods (1) and (2). The condensation intermediate in these reactions was dihydropyridone compound and its oxidation to pyridone gave a poor yield of the product but the oxidation product was obtained directly when the substituent in the 4-position was piperonal. Attempt to introduce one more substituent into the pyridine ring by the method (2) did not materialize. Oxidation of 1, 4-dihydropyridine derivatives (XXa∼b), obtained by method (3), to pyridine derivatives (XXIa∼b) was not effected by the use of dilute nitric acid, chromic acid, palladium black, or palladium carbon, and it is interesting that the oxidation product was finally obtained by heating the dihydro compounds in a sealed tube with mercury acetate to above the melting point of them.