title: The development of 2-benzimidazole substituted pyrimidine based inhibitors of lymphocyte specific kinase (Lck).
abstract: This communication details the synthesis, biological activity, and binding mode of a novel class of 2-benzimidazole substituted pyrimidines. The most potent analogs disclosed showed low nanomolar activity for the inhibition of Lck kinase and a representative analog was co-crystallized with Hck (a structurally related member of the Src family kinases).
authors.affiliation: Procter and Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Rd., Mason, OH 45040, USA. Mark.Sabat@Takedasd.com <Mark.Sabat@Takedasd.com>
authors.forename: Mark
authors.initials: M
authors.lastname: Sabat
authors.forename: John C
authors.initials: JC
authors.lastname: VanRens
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Laufersweiler
authors.forename: Todd A
authors.initials: TA
authors.lastname: Brugel
authors.forename: Jennifer
authors.initials: J
authors.lastname: Maier
authors.forename: Adam
authors.initials: A
authors.lastname: Golebiowski
authors.forename: Biswanath
authors.initials: B
authors.lastname: De
authors.forename: Vijayasurian
authors.initials: V
authors.lastname: Easwaran
authors.forename: Lily C
authors.initials: LC
authors.lastname: Hsieh
authors.forename: Richard L
authors.initials: RL
authors.lastname: Walter
authors.forename: Marlene J
authors.initials: MJ
authors.lastname: Mekel
authors.forename: Artem
authors.initials: A
authors.lastname: Evdokimov
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Janusz
mesh_terms: D001562:Benzimidazoles / Q000737:chemistry*; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D007376:Interleukin-2 / Q000378:metabolism; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis / Q000378:metabolism; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051572:Proto-Oncogene Proteins c-hck / Q000737:chemistry / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D007376:Interleukin-2; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C031000:benzimidazole; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051572:Proto-Oncogene Proteins c-hck; C030986:pyrimidine