Synthesis and SAR of novel imidazoquinoxaline-based Lck inhibitors: improvement of cell potency

Ping Chen; Edwin J Iwanowicz; Derek Norris; Henry H Gu; James Lin; Robert V Moquin; Jagabandhu Das; John Wityak; Steven H Spergel; Henry de Fex; Suhong Pang; Sydney Pitt; Ding Ren Shen; Gary L Schieven; Joel C Barrish

doi:10.1016/s0960-894x(02)00677-7

Synthesis and SAR of novel imidazoquinoxaline-based Lck inhibitors: improvement of cell potency

Bioorg Med Chem Lett. 2002 Nov 4;12(21):3153-6. doi: 10.1016/s0960-894x(02)00677-7.

Authors

Ping Chen¹, Edwin J Iwanowicz, Derek Norris, Henry H Gu, James Lin, Robert V Moquin, Jagabandhu Das, John Wityak, Steven H Spergel, Henry de Fex, Suhong Pang, Sydney Pitt, Ding Ren Shen, Gary L Schieven, Joel C Barrish

Affiliation

¹ Discovery Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543, USA. ping.chen@bms.com

PMID: 12372522
DOI: 10.1016/s0960-894x(02)00677-7

Abstract

A series of anilino(imidazoquinoxaline) analogues bearing solubilizing side chains at the 6- and 7-positions of the fused phenyl ring has been prepared and evaluated for inhibition against Lck enzyme and of T-cell proliferation. Significant improvement of the cellular activity was achieved over the initial lead, compound 2.

MeSH terms

Cell Division / drug effects
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Humans
Indicators and Reagents
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / antagonists & inhibitors*
Quinoxalines / chemical synthesis*
Quinoxalines / pharmacology*
Structure-Activity Relationship
T-Lymphocytes / drug effects

Substances

Enzyme Inhibitors
Indicators and Reagents
Quinoxalines
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)