Heterocyclic analogs of the antihypertensive .beta.-adrenergic blocking agent (S)-2-[3-(tert-butylamino)-2-hydroxypropoxy]-3-cyanopyridine

Abstract

The synthesis of a series of isoelectronic analogues of (S)-2-[3-(tert-butylamino)-2-hydroxypropoxy]-3-cyanopyridine (1) are described; included in this group are examples of thiazole, isothiazole, thiadiazole, pyrazine, and the structurally related naphthyridines. All of the compounds are similar to 1 in that they contain a cyano group ortho to the aminohydroxypropoxy side chain and meta to the nitrogen heteroatom. In addition, several related examples, having additional nuclear substituents and/or groups other than CN in the position adjacent to the aminohydroxypropoxy group, were prepared, and beta-adrenoceptor antagonist activity and vasodilating potency were determined. Three compounds, thiazole 2 and isothiazoles 3 and 27, effectively lowered mean arterial pressure in the SH rat at 5 mg/kg. Compounds 2, 3, and 27 increased iliac blood flow and exhibited beta-adrenergic blocking properties in the dog.

Facile Synthesis and Antimicrobial Activities of 5H-[1,2,4]triazol[1,3,4]thiadiazine Derivatives

“…The solid separated out was filtered, washed thoroughly with water and crystallized from ethanol (Scheme 1). Synthesis of 5H- [1,2,4]triazolo [3,4-b] [1,3,4] thiadiazines (4a-o) A mixture of compound 3 (10 mmol), catalytic amount of hydrazine hydrate (1 mmol) and DMF (5 mL) as an energy transfer medium was exposed to microwave irradiations for 30 seconds. After that β-diketone/ β-ketoester (10 mmol) was added to the reaction mixture and again exposed to microwave irradiations intermittently at 30 seconds for three minutes.…”

“…All data were found in accordance with the proposed structures of synthesized compounds. All the 5H- [1,2,4]triazolo [3,4-b] [1,3,4]thiadiazine derivatives (4a-o) along with some standard antibiotics and antifungal drugs were screened for their antimicrobial activities against selected bacteria and fungus. All the antimicrobial activity results are summarized in Table 1.…”

“…The yield obtained from microwave methods was better as compared to conventional method. The target compounds, 5H- [1,2,4]triazolo [3,4-b] [1,3,4]thiadiazine derivatives (4a-o) were prepared by environmental friendly method (Scheme 2) in which the mixture of intermediate compound 3, β-diketone / β-ketoester and catalytic amount of hydrazine hydrate irradiated in microwave oven. The purity of the compounds was checked by TLC.…”

“…In general, biological active compounds are derived from heterocyclic structures. Heterocycles containing 1,2,4-triazole and 1,3,4-thiadiazine nucleus have been well studied for a number of pathological conditions including inflammation 1,2 , hypertension 3 and aching 4 . The 1,3,4-thiadiaznie derivatives in which 1,4-thiazines fused with 1,2,4-triazole nucleus are important scaffold in several natural and synthetic compounds of significant pharmacological properties and also have structural similarity with biologically most active phenothiazines in having fold along N-S axis 5 .…”

Synthesis and antioxidant evaluation of some new pyridines

“…Many naturally occurring as well as synthetic compounds containing the pyridine scaffold exhibit interesting pharmacological properties [6][7][8][9][10]. Furthermore, pyridine is one of the most popular N-heteroaromatics incorporated into the structure of many pharmaceuticals.…”