The influence of substituents in 3-position on the activity of chroman-type potassium channel activators.
Swern oxidation of chromanol 1 led to ketone 3 with concomitant chlorination of the adjacent 4-position. Using Leuckart conditions, chromanone 2 was converted to enamine 5.--4-Bromochromene-3-carbaldehyde 8, which was obtained by Vilsmeier-Arnold reaction from 7, turned out to be a suitable intermediate for the insertion of the pyridone residue. 3-Chloro derivatives 16 and 19 resulted on heating the mesylate or tosylate with LiCl in DMF. Bromination of chromene 20 led to 21.--All compounds were tested for oral antihypertensive activity in spontaneously hypertensive rats with a dose of 1 mg/kg.
Bergmann
R
R
Preclinical Pharmaceutical Research, E. Merck, Darmstadt, Germany.
Gericke
R
R
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002839:Chromans / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR
D000959:Antihypertensive Agents; D002839:Chromans; D015221:Potassium Channels