Synthesis and antihypertensive activity of 4-(1,2-dihydro-2-oxo-1-pyridyl)-2H-1-benzopyrans and related compounds, new potassium channel activators.

摘要: The synthesis and antihypertensive activity of 4-(1,2-dihydro-2-oxo-1-pyridyl)-2H-1-benzopyran-3-ols are described. unsubstituted pyridone adduct lead compound 7e is highly active, with substituents on the ring leading to a decrease in activity. Strongly electron-withdrawing at C-6 position required for optimal When 2-pyridone replaced by other heterocycles such as 4-pyridone, pyrimidone, pyridazinone, pyrazinone, 1,4-butanesultam, maintained. removal 3-hydroxy function (----17a) does not significantly reduce elimination water from chromanols leads formation chromenes, which among most potent antihypertensives known. influence diverse substituents, particular heterocyclic was investigated 4-(2-oxo-1-pyrrolidinyl)chroman-3-ol series. Chromanols esterified group short-chain acids, maintain their epoxidation chromene double bond also produces active compounds. rearrangement epoxides 22 3-keto compounds 23 enol derivatives 25. reduction ketone 23a cis-chromanol 7ab along its trans isomer 7e. All were tested oral spontaneously hypertensive rats dose 1 mg/kg; selected ED30 values well duration effect determined. 4-(1,2-Dihydro-2-oxo-1-pyridyl)-2,2-dimethyl-2H-1-benzopyran-6- carbonitrile (18a) under development coronary vasodilator drug treating angina pectoris.