title: Disubstituted pyrimidines as Lck inhibitors.
abstract: We have developed a family of 4-benzimidazolyl-N-piperazinethyl-pyrimidin-2-amines that are subnanomolar inhibitors of Lck. A subset of these Lck inhibitors, with heterocyclic substituents at the benzimidazole C5, are also low-nanomolar inhibitors of cellular IL2 release.
authors.affiliation: Merck Research Laboratories, Merck & Co., PO Box 2000, Rahway, NJ 07065, United States. julianne_hunt@merck.com
authors.forename: Julianne A
authors.initials: JA
authors.lastname: Hunt
authors.forename: Richard T
authors.initials: RT
authors.lastname: Beresis
authors.forename: Joung L
authors.initials: JL
authors.lastname: Goulet
authors.forename: Mark A
authors.initials: MA
authors.lastname: Holmes
authors.forename: Xinfang J
authors.initials: XJ
authors.lastname: Hong
authors.forename: Ernest
authors.initials: E
authors.lastname: Kovacs
authors.forename: Sander G
authors.initials: SG
authors.lastname: Mills
authors.forename: Rowena D
authors.initials: RD
authors.lastname: Ruzek
authors.forename: Frederick
authors.initials: F
authors.lastname: Wong
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Hermes
authors.forename: Young-Whan
authors.initials: YW
authors.lastname: Park
authors.forename: Scott P
authors.initials: SP
authors.lastname: Salowe
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Sonatore
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.forename: Andrea
authors.initials: A
authors.lastname: Woods
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Zaller
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sinclair
mesh_terms: D020128:Inhibitory Concentration 50; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D007376:Interleukin-2; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)