Bioorg Med Chem Lett
October 2011
On the basis of the previously reported benzimidazole 1,3'-bipyrrolidine benzamides (1), a series of related pyrrolidin-3-yl-N-methylbenzamides were synthesized and evaluated as H(3) receptor antagonists. In particular, compound 32 exhibits potent H(3) receptor binding affinity, improved pharmaceutical properties and a favorable in vivo profile.
View Article and Find Full Text PDFPrevious studies with perzinfotel (1), a potent, selective, competitive NMDA receptor antagonist, showed it to be efficacious in inflammatory and neuropathic pain models. To increase the low oral bioavailability of 1 (3-5%), prodrug derivatives (3a-h) were synthesized and evaluated. The oxymethylene-spaced diphenyl analogue 3a demonstrated good stability at acidic and neutral pH, as well as in simulated gastric fluid.
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