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

Jeewoo Lee, Sang Uk Kang, Hyun Kyung Choi, Jiyoun Lee, Ju Ok Lim, Min Jung Kil, Mi Kyung Jin, Kang Pil Kim, Jong Hyuk Sung, Suk Jae Chung, Hee Jin Ha, Young Ho Kim, Larry V. Pearce, Richard Tran, Daniel J. Lundberg, Yun Wang, Attila Toth, Peter M. Blumberg

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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 NC-hydroxy thiourea analogues (12, 13) showed excellent analgesic activities in the acetic acid writhing assay compared to the parent thiourea analogues.

Original languageEnglish
Pages (from-to)2291-2297
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Volume14
Issue number9
DOIs
Publication statusPublished - 2004 May 3

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Lee, J., Kang, S. U., Choi, H. K., Lee, J., Lim, J. O., Kil, M. J., Jin, M. K., Kim, K. P., Sung, J. H., Chung, S. J., Ha, H. J., Kim, Y. H., Pearce, L. V., Tran, R., Lundberg, D. J., Wang, Y., Toth, A., & Blumberg, P. M. (2004). 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. Bioorganic and Medicinal Chemistry Letters, 14(9), 2291-2297. https://doi.org/10.1016/j.bmcl.2004.02.002