title: N-(3-(phenylcarbamoyl)arylpyrimidine)-5-carboxamides as potent and selective inhibitors of Lck: structure, synthesis and SAR.
abstract: N-3-(Phenylcarbamoyl)arylpyrimidine-5-carboxamides are a novel class of selective Lck inhibitors. This series of compounds derives its selectivity from a hydrogen bond with the gatekeeper Thr316 of the enzyme. X-ray co-crystal structural data, structure-activity relationships, and the synthesis of these inhibitors are reported herein.
authors: Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA. holly.deak@amgen.com
authors: Holly L
authors: HL
authors: Deak
authors: John R
authors: JR
authors: Newcomb
authors: Joseph J
authors: JJ
authors: Nunes
authors: Christina
authors: C
authors: Boucher
authors: Alan C
authors: AC
authors: Cheng
authors: Erin F
authors: EF
authors: DiMauro
authors: Linda F
authors: LF
authors: Epstein
authors: Paul
authors: P
authors: Gallant
authors: Brian L
authors: BL
authors: Hodous
authors: Xin
authors: X
authors: Huang
authors: Josie H
authors: JH
authors: Lee
authors: Vinod F
authors: VF
authors: Patel
authors: Stephen
authors: S
authors: Schneider
authors: Susan M
authors: SM
authors: Turci
authors: Xiaotian
authors: X
authors: Zhu
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors*; D008968:Molecular Conformation; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013912:Threonine / Q000737:chemistry
chemical_list: D000577:Amides; D011743:Pyrimidines; D013912:Threonine; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)