European Journal of Medicinal Chemistry 2009-01-01

Conformationally constrained analogues ofN′-(4-tert-butylbenzyl)-N-(4-methylsulfonylaminobenzyl)thiourea as TRPV1 antagonists

Ju-Ok Lim, Mi-Kyoung Jin, HyungChul Ryu, Dong Wook Kang, Jeewoo Lee, Larry V. Pearce, Richard Tran, Attila Toth, Peter M. Blumberg, Ju-Ok Lim, Mi-Kyoung Jin, HyungChul Ryu, Dong Wook Kang, Jeewoo Lee, Larry V Pearce, Richard Tran, Attila Toth, Peter M Blumberg

Index: Eur. J. Med. Chem. 44(1) , 322-31, (2009)

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Abstract

A series of bicyclic analogues having indan and tetrahydronaphthalene templates in the A-region were designed as conformationally constrained analogues of our previously reported potent TRPV1 antagonists ( 1, 3). The activities for rat TRPV1 of the conformationally restricted analogues were moderately or markedly diminished, particularly in the case of the tetrahydronaphthalene analogues. The analysis indicated that steric constraints at the benzylic position in the bicyclic analogues may be an important factor for their unfavorable interaction with the receptor.