Synthesis and hypotensive activity of N-alkyl-N''-cyano-N'-pyridylguanidines

Abstract

A variety of N-alkyl-N'-pyridyl-N"-cyanoguanidines III was prepared as potential bioisosteres of hypotensive N-alkyl-N'-pyridylthioureas Ia. Optimal activity of the N,N'-disubstituted cyanoguanidines III was assoicated with the presence of four to seven carbon branched alkyl and 3- or 4-pyridyl groups. Maximum potency was displayed by N-tert-pentyl-N'-3 pyridyl-N"-cyanoguanidine (20). This compound proved to be 200 times more potent than the corresponding thiourea in hypertensive rats and dogs. In comparison with guancydine, which is the de-3-pyridyl analogue of 20, a 150-fold increase of potency in spontaneously hypertensive rats was obtained with 20 and its tert-butyl analogue 19. The observed activity appears to be due to direct vascular relaxation. On a weight basis compounds 19, 20, 50, and 101 compared favorably with hydralazine.

Maintenance of functional activity of human pulmonary arteries after cryopreservation

“…Nevertheless all constricting agents tested, i.e., noradrenaline Figure 2a), P-1075 (Petersen et al, 1978; Figure 2b) and SDZ PCO 400 (Quast et al, 1990; Figure 2c) produced about 40-50% relaxation of precontracted arterial rings from both groups and the apparent pD2 values were slightly reduced in frozen/thawed arteries (Table 1). Marked differences of both efficacy and potency between fresh and frozen/ thawed arteries were observed when cromakalim (Hamilton et al, 1986) was investigated (Figure 2d).…”

Effect of MgATP on pinacidil‐induced displacement of glibenclamide from the sulphonylurea receptor in a pancreatic β‐cell line and rat cerebral cortex

“…Microsomes were prepared from monolayers on 94 mm petri dishes (passage [77][78][79][80][81][82][83][84][85][86][87][88][89][90] (Wohl, 1970;Petersen et al, 1978 and other additions as described in the Results section. Unless stated otherwise, incubations were carried out for 2 h at room temperature and were terminated as described by Glossmann & Ferry (1983) with minor modifications.…”

Similarities in Bioanalogous Structural Transformation Patterns among Various Bioactive Compound Series

“…Systematization is also convenient to make computers recognize otherwise complicated transformation patterns such as those between open-chain amides and cyclic dicarboximides. The fact that, the structural transformation patterns from open-chain herbicides (1-3, 72) to cyclic imide-type agrochemicals (67)(68)(69)73) and those from openchain CNS-active amides (80)(81)(82) to cyclic CNS-agents (77)(78)(79) are identical shown as the the pattern from structure 94 to 95, is not easily and straightforwardly recognizable by the human brain. We are working on a project to construct such a system named EMIL, ExampleMediated-Innovation-for-Lead-Evolution, and the EMIL database.…”