The development of novel 1,2-dihydro-pyrimido[4,5-c]pyridazine based inhibitors of lymphocyte specific kinase (Lck)

Mark Sabat; John C Vanrens; Todd A Brugel; Jennifer Maier; Matthew J Laufersweiler; Adam Golebiowski; Biswanath De; Vijayasurian Easwaran; Lily C Hsieh; Jeff Rosegen; Steve Berberich; Eric Suchanek; Michael J Janusz

doi:10.1016/j.bmcl.2006.05.072

The development of novel 1,2-dihydro-pyrimido[4,5-c]pyridazine based inhibitors of lymphocyte specific kinase (Lck)

Bioorg Med Chem Lett. 2006 Aug 15;16(16):4257-61. doi: 10.1016/j.bmcl.2006.05.072. Epub 2006 Jun 6.

Authors

Mark Sabat¹, John C Vanrens, Todd A Brugel, Jennifer Maier, Matthew J Laufersweiler, Adam Golebiowski, Biswanath De, Vijayasurian Easwaran, Lily C Hsieh, Jeff Rosegen, Steve Berberich, Eric Suchanek, Michael J Janusz

Affiliation

¹ Procter and Gamble Pharmaceuticals, Health Care Research Center, Mason, OH 45040, USA. sabat.mp@pg.com

PMID: 16757169
DOI: 10.1016/j.bmcl.2006.05.072

Abstract

This communication details the synthesis, biological activity, and proposed binding mode of a novel class of tri-cyclic derivatives of 1,2-dihydro-pyrimido[4,5-c]pyridazines 1 and 2. The most potent analogs disclosed showed low nanomolar activity for the inhibition of Lck kinase.

MeSH terms

Drug Design
Drug Industry / methods*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Inhibitory Concentration 50
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / antagonists & inhibitors*
Lymphocytes / metabolism
Models, Chemical
Models, Molecular
Pyridazines / chemistry*
Pyridazines / pharmacology
Pyrimidines / chemistry*
Pyrimidines / pharmacology
Ribonucleosides / chemistry*
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Pyridazines
Pyrimidines
Ribonucleosides
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)