N-[4-(Methylsulfonylamino) benzyl] thiourea analogues as vanilloid receptor antagonists: analysis of structure–activity relationships for the 'C-Region'

J Lee, SU Kang, JO Lim, HK Choi, M Jin, A Toth…

Index: Lee, Jeewoo; Kang, Sang-Uk; Lim, Ju-Ok; Choi, Hyun-Kyung; Jin, Mi-Kyung; Toth, Attila; Pearce, Larry V.; Tran, Richard; Wang, Yun; Szabo, Tamas; Blumberg, Peter M. Bioorganic and Medicinal Chemistry, 2004 , vol. 12, # 2 p. 371 - 385

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Citation Number: 34

Abstract

We recently reported that N-(4-t-butylbenzyl)-N′-[4-(methylsulfonylamino) benzyl] thiourea (2) was a high affinity antagonist of the vanilloid receptor with a binding affinity of Ki= 63 nM and an antagonism of Ki= 53.9 nM in rat VR1 heterologously expressed in Chinese hamster ovary (CHO) cells (Mol. Pharmacol. 2002, 62, 947–956). In an effort to further improve binding affinity and antagonistic potency, we have modified the C-region of the lead 4-t- ...