Discovery and initial SAR of 2-amino-5-carboxamidothiazoles as inhibitors of the Src-family kinase p56(Lck)

John Wityak; Jagabandhu Das; Robert V Moquin; Zhongqi Shen; James Lin; Ping Chen; Arthur M Doweyko; Sidney Pitt; Suhong Pang; Ding Ren Shen; Qiong Fang; Henry F de Fex; Gary L Schieven; Steven B Kanner; Joel C Barrish

doi:10.1016/j.bmcl.2003.08.054

Discovery and initial SAR of 2-amino-5-carboxamidothiazoles as inhibitors of the Src-family kinase p56(Lck)

Bioorg Med Chem Lett. 2003 Nov 17;13(22):4007-10. doi: 10.1016/j.bmcl.2003.08.054.

Authors

John Wityak¹, Jagabandhu Das, Robert V Moquin, Zhongqi Shen, James Lin, Ping Chen, Arthur M Doweyko, Sidney Pitt, Suhong Pang, Ding Ren Shen, Qiong Fang, Henry F de Fex, Gary L Schieven, Steven B Kanner, Joel C Barrish

Affiliation

¹ Department of Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. jwityak@gnf.org

PMID: 14592495
DOI: 10.1016/j.bmcl.2003.08.054

Abstract

A novel series of 2-amino-5-carboxamidothiazoles were identified as inhibitors of Lck. Structure-activity studies demonstrate the structural requirements for potent Lck activity. Cyclopropylamide 11d is a potent Lck inhibitor having sub-micromolar activity in a PBL proliferation assay.

MeSH terms

Amino Acid Sequence
Binding Sites
Drug Design
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / antagonists & inhibitors*
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / chemistry
Models, Molecular
Molecular Structure
Structure-Activity Relationship
Thiazoles / chemical synthesis*
Thiazoles / pharmacology*

Substances

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