Discovery of 2-amino-heteroaryl-benzothiazole-6-anilides as potent p56(lck) inhibitors

Bioorg Med Chem Lett. 2003 Aug 4;13(15):2587-90. doi: 10.1016/s0960-894x(03)00511-0.

Abstract

A series of structurally novel benzothiazole based small molecule inhibitors of p56(lck) was prepared to elucidate their structure-activity relationships (SAR), selectivity and cell activity in the T-cell proliferation assay. BMS-350751 (2) and BMS-358233 (3) are identified as potent Lck inhibitors with excellent cellular activities against T-cell proliferation.

MeSH terms

  • Anilides / chemical synthesis*
  • Anilides / pharmacology*
  • Cell Division / drug effects
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / antagonists & inhibitors*
  • Models, Molecular
  • Protein Conformation
  • Structure-Activity Relationship
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / enzymology
  • Thiazoles / chemical synthesis*
  • Thiazoles / pharmacology*

Substances

  • Anilides
  • Enzyme Inhibitors
  • Thiazoles
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)