Synthesis and biological activity of trans-(.+-.)-N-methyl-2-(3-pyridyl)-2-tetrahydrothiopyrancarbothioamide 1-oxide (RP 49356) and analogs: a new class of potassium channel opener

Abstract

The synthesis and biological activity of trans-(+-)-N-methyl-2-(3-pyridyl)-2-tetrahydrothiopyrancarbothioamid+ ++ e 1-oxide (8a, RP 49356) and analogues is reported. These compounds constitute a new structural class of K(+)-channel opener. The effects of changes in pyridyl group, thioamide, and thiane ring on in vitro K(+)-channel opening reactivity are discussed. A 3-pyridyl or 3-quinolyl group, a small N-alkyl thioamide function, and a thiane oxide ring, in which the sulfoxide is in a trans relationship to the thioamide, are preferred for activity. Selected compounds were tested intravenously in the normotensive anaesthetized rat for hypotensive effects, and the activities reflect their in vitro K(+)-channel opening activity. This led to further evaluation of compound 8a and the selection of the (-)-enantiomer 8b (RP 52891) for development as an antihypertensive and antianginal agent.

Ruthenium(II) half-sandwich complexes containing thioamides: Synthesis, structures and catalytic transfer hydrogenation of ketones

“…The only side product formed is acetone, which is easily removed by distillation during workup. (4) are grown by slow evaporation at room temperature. A single crystal of suitable size was mounted on the top of a glass fiber, and transferred to a Stoe IPDS diffractometer using monochromated MoKa radiation.…”

One-pot synthesis, biological evaluation, and docking study of new chromeno-annulated thiopyrano[2,3-c]pyrazoles

“…Derivatives of thiopyran, and thiopyrano-fused pyrazoles and other heterocycles, on the other hand, constitute a class of sulfur heterocycle analogs of the possessing significant bioactivities [16][17][18][19][20]. RP 49356 is a K + channel opener [17].…”

“…RP 49356 is a K + channel opener [17]. Thiopyran derivatives are modulators of estrogen receptors, and possess a high dopamine receptor-binding affinity [21,22].…”

Synthesis of Benzofuran, Benzothiophene, and Benzothiazole‐Based Thioamides and their Evaluation as KATP Channel Openers

“…All compounds were investigated with respect to their binding affinity for the SUR2B-type K ATP channels using [ 3 H]P1075 as radioligand. Selected compounds were also tested as agonists in intact cells using DiBAC 4 (3) and DyeB (R7260) as membrane potential dyes. Remarkable affinity for SUR2B/Kir6.1 channels in the single-digit micromolar range was observed.…”

“…In pursuing this goal, we were guided by the idea that heterocyclic skeletons, hitherto unused in K ATP -active drugs, might be promising candidates for the development of new and selective PCOs. For this purpose we combined, for the first time, the thioamide pharmacophore [3] with the benzofuran, benzothiophene, and benzothiazole skeletons.…”