Aryl cyanoguanidine potassium channel openers

Cardioselective Anti-Ischemic ATP-Sensitive Potassium Channel Openers. 3. Structure-Activity Studies on Benzopyranyl Cyanoguanidines; Modification of the Cyanoguanidine Portion

“…These data are consistent with the requirement of an aniline nitrogen for optimal anti-ischemic potency. Insertion of a methylene unit (8, 9) and a nitrogen atom (10) between the pendant phenyl ring and the urea nitrogen leads to diminished anti-ischemic potency (compare 3 vs 8 and 10, 4 vs 9). These data suggest that optimal anti-ischemic potency is achieved with a phenylurea/ cyanoguanidine moiety.…”

“…The modest 50-60% yield of this step is due to incomplete reaction. Details of this method have been described.5-7 Method B involves conversion of the amino alcohol (43) to a common intermediate (5) which is then reacted with the appropriate amine to provide the desired products (8,10,12) (Scheme l).8 Both racemic and chiral forms of benzopyranyl amine 43 are described.5 9 The arythiourea employed in method A (Scheme 1) can be readily prepared by treatment of arylisothiocyanate with monosodium cyanamide.7The acyl analog 7 was prepared from the amine 43 by treatment with phenylacetyl chloride in aqueous sodium bicarbonate. The acid analogs 32 and 33 were obtained by saponification of the esters 30 and 31, ©…”

Cardioselective anti-ischemic ATP-sensitive potassium channel openers

“…were determined by measurement of IC50 values for relaxation of the methoxamine-contracted rat aorta, as described previously.5 The anti-ischemic potencies in vitrowere determined by measurement of EC25 values for increase in time to contracture in globally ischemic isolated rat hearts.6 Time to contracture is defined as the time necessary during total global ischemia to increase end diastolic pressure by 5 mmHg.6 As exemplified by the comparison between phenylcyanoguanidine analog 5 and cromakalim (1), we found no correlation between vasorelaxant and anti-ischemic potencies (Table I). The phenylcyanoguanidine analog 5 was equipotent to cromakalim as an anti-ischemic agent in vitro, despite being 40-fold less potent as a vasorelaxing agent.…”

Efficient access to novel 5-aryloyl-1H-pyrano[2,3-d:6,5-d']dipyrimidine-2,4,6,8(3H,5H,7H,9H)-tetraones and their sulfur analogs in water

“…6 Pyran derivatives are of considerable interest as they possess a wide range of biological properties such as spasmolytic, diuretic, antiallergic, anticoagulant, anticancer, and antianaphylactic activity, etc. [7][8][9] Polyfuctionalized pyran derivatives are common structural subunits in variety of important natural products. [8][9][10][11] In addition, they can be used as cognitive enhancers, for the treatment of neurodegenerative diseases.…”