1437872-65-5Relevant academic research and scientific papers
Modular, efficient synthesis of asymmetrically substituted piperazine scaffolds as potent calcium channel blockers
Borzenko, Andrey,Pajouhesh, Hassan,Morrison, Jerrie-Lynn,Tringham, Elizabeth,Snutch, Terrance P.,Schafer, Laurel L.
, p. 3257 - 3261 (2013)
A novel approach to the synthesis of substituted piperazines and their investigation as N-type calcium channel blockers is presented. A common scaffold exhibiting high activity as N-type blockers is N-substituted piperazine. Using recently developed titanium and zirconium catalysts, we describe the efficient and modular synthesis of 2,5-asymmetrically disubstituted piperazines from simple amines and alkynes. The method requires only three isolation/purification protocols and no protection/deprotection steps for the diastereoselective synthesis of 2,5-dialkylated piperazines in moderate to high yield. Screening of the synthesized piperazines for N-type channel blocking activity and selectivity shows the highest activity for a compound with a benzhydryl group on the nitrogen (position 1) and an unprotected alcohol-functionalized side chain.
