Evaluation and synthesis of 7-arylhydroxymethyltriazolopyridines as potential cardiovascular agents

Abstract

7-Arylhydroxymethyltriazolopyridines 3a-c and 4a-d were synthesized by regioselective lithiation of [1,2,3]triazolo[1,5-a]pyridines 1 and 2 and subsequent trapping of the 7-lithioderivatives formed using aryl aldehydes as electrophiles. The structural relationship between compounds 3a-c and 4a-d and arylethanolamines suggested their consideration as potential cardiovascular agents. A preliminary evaluation as vascular smooth muscle relaxants was carried out. These compounds did not act as α 1 -adrenoceptor antagonists and were unable to block calcium entry through voltage-dependent calcium channels.

Deprotonative Magnesation and Cadmation of [1,2,3]Triazolo[1,5-a]pyridines

“…Modification of organometallic compounds in order to get more chemoselective bases for the deprotonation of sensitive substrates is a challenging area. Combining lithium and magnesium organometallics in lithium triorganomagnesate (Bu 3 MgLi) resulted in good chemoselectivity when compared to those of lithium bases, allowing reactions to be carried out in similar yields at −10 °C instead of −40 °C when using classical lithium bases. ,,,, Using cadmium instead of magnesium and TMP instead of butyl groups afforded an efficient and chemoselective base, which was able to regioselectively deprotonate [1,2,3]triazolo[1,5- a ]pyridines substituted or not at the 3 position. Polydeprotonation also proved possible in some cases.…”