New pyrazolo[1,5a]pyrimidines as orally active inhibitors of Lck

Nina Gommermann; Peter Buehlmayer; Anette von Matt; Werner Breitenstein; Keiichi Masuya; Bernard Pirard; Pascal Furet; Sandra W Cowan-Jacob; Gisbert Weckbecker

doi:10.1016/j.bmcl.2010.04.112

New pyrazolo[1,5a]pyrimidines as orally active inhibitors of Lck

Bioorg Med Chem Lett. 2010 Jun 15;20(12):3628-31. doi: 10.1016/j.bmcl.2010.04.112. Epub 2010 Apr 29.

Authors

Nina Gommermann¹, Peter Buehlmayer, Anette von Matt, Werner Breitenstein, Keiichi Masuya, Bernard Pirard, Pascal Furet, Sandra W Cowan-Jacob, Gisbert Weckbecker

Affiliation

¹ Novartis Institute of Biomedical Research, Forum 1, Novartis Campus, Basel, Switzerland. nina.gommermann@novartis.com

PMID: 20483608
DOI: 10.1016/j.bmcl.2010.04.112

Abstract

A novel series of pyrazolo[1,5a]pyrimidines was optimized to target lymphocyte-specific kinase (Lck). An efficient synthetic route was developed and SAR studies toward activity and selectivity are described, leading to Lck inhibitors with enzymatic, cellular and in vivo potency.

MeSH terms

Administration, Oral
Animals
Humans
Interleukin-2 / metabolism
Lymphocyte Activation / drug effects
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / antagonists & inhibitors*
Mice
Microsomes, Liver / metabolism
Pyrimidines / pharmacology
Rats
Structure-Activity Relationship

Substances

Interleukin-2
Pyrimidines
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)