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ID: ALA1149228

Journal: Bioorg Med Chem Lett

Title: Analysis of structure-activity relationships for the 'B-region' of N-(3-acyloxy-2-benzylpropyl)-N(')-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists: discovery of an N-hydroxythiourea analogue with potent analgesic activity.

Authors: Lee J, Kang SU, Choi HK, Lee J, Lim JO, Kil MJ, Jin MK, Kim KP, Sung JH, Chung SJ, Ha HJ, Kim YH, Pearce LV, Tran R, Lundberg DJ, Wang Y, Toth A, Blumberg PM.

Abstract: The structural modifications on the B-region of the potent and high affinity vanilloid receptor (VR1) lead ligand N-(3-acyloxy-2-benzylpropyl)-N(')-[4-(methylsulfonylamino)benzyl]thiourea were investigated by the replacement of the thiourea with diverse isosteric functional groups. Structure-activity analysis indicated that the A-region in this series was the primary factor in determining the agonistic/antagonistic activities regardless of the B-region. The N(C)-hydroxy thiourea analogues (12, 13) showed excellent analgesic activities in the acetic acid writhing assay compared to the parent thiourea analogues.

CiteXplore: 15081027

DOI: 10.1016/j.bmcl.2004.02.002