title: Discovery and initial SAR of imidazoquinoxalines as inhibitors of the Src-family kinase p56(Lck).
abstract: We have identified a novel series of 1,5-imidazoquinoxalines as inhibitors of Lck with excellent potency (IC50s<5 nM) as well as good cellular activity against T-cell proliferation (IC50s<1 microM). Structure-activity studies demonstrate the requirement for the core heterocycle in addition to an optimal 2,6-disubstituted aniline group.
authors: Department of Discovery Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543, USA. ping.chen@bms.com
authors: Ping
authors: P
authors: Chen
authors: Derek
authors: D
authors: Norris
authors: Edwin J
authors: EJ
authors: Iwanowicz
authors: Steven H
authors: SH
authors: Spergel
authors: James
authors: J
authors: Lin
authors: Henry H
authors: HH
authors: Gu
authors: Zhongqi
authors: Z
authors: Shen
authors: John
authors: J
authors: Wityak
authors: Tai-An
authors: TA
authors: Lin
authors: Suhong
authors: S
authors: Pang
authors: Henry F
authors: HF
authors: De Fex
authors: Sidney
authors: S
authors: Pitt
authors: Ding Ren
authors: DR
authors: Shen
authors: Arthur M
authors: AM
authors: Doweyko
authors: Donna A
authors: DA
authors: Bassolino
authors: Jacques Y
authors: JY
authors: Roberge
authors: Michael A
authors: MA
authors: Poss
authors: Bang-Chi
authors: BC
authors: Chen
authors: Gary L
authors: GL
authors: Schieven
authors: Joel C
authors: JC
authors: Barrish
mesh_terms: D000818:Animals; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D008968:Molecular Conformation; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D011810:Quinoxalines; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases