@article { ISI:000318976100026,
	title = {Modular, efficient synthesis of asymmetrically substituted piperazine scaffolds as potent calcium channel blockers},
	journal = {Bioorganic \& Medicinal Chemistry Letters },
	volume = {23},
	number = {11},
	year = {2013},
	month = {JUN 1},
	pages = {3257-3261},
	abstract = {<p>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. (C) 2013 Elsevier Ltd. All rights reserved.</p>},
	issn = {0960-894X},
	doi = {10.1016/j.bmcl.2013.03.114},
	author = {Borzenko, Andrey and Pajouhesh, Hassan and Morrison, Jerrie-Lynn and Tringham, Elizabeth and Snutch, Terrance P. and Schafer, Laurel L.}
}
