Design, synthesis, and pharmacological evaluation of conformationally constrained analogues of N, N'-diaryl-and N-aryl-N-aralkylguanidines as potent inhibitors of …

…, D Berlove, S Connaughton, JB Fischer…

Index: Maillard, Michel C.; Perlman, Michael E.; Amitay, Oved; Baxter, Deborah; Berlove, David; Connaughton, Sonia; Fischer, James B.; Guo, Jun Qing; Hu, Lain-Yen; McBurney, Robert N.; Nagy, Peter I.; Subbarao, Katragadda; Yost, Elizabeth A.; Zhang, Lu; Durant, Graham J. Journal of Medicinal Chemistry, 1998 , vol. 41, # 16 p. 3048 - 3061

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Citation Number: 33

Abstract

In the present investigation, the rationale for the design, synthesis, and biological evaluation of potent inhibitors of neuronal Na+ channels is described. N, N'-Diaryl-and N-aryl-N- aralkylguanidine templates were locked in conformations mimicking the permissible conformations of the flexible diarylguanidinium ion (AS+, AA+, SS+). The resulting set of constrained guanidines termed “lockamers”(cyclophane, quinazoline, ...