title: Utilization of a nitrogen-sulfur nonbonding interaction in the design of new 2-aminothiazol-5-yl-pyrimidines as p38α MAP kinase inhibitors.
abstract: The design, synthesis, and structure-activity relationships (SAR) of a series of 2-aminothiazol-5-yl-pyrimidines as novel p38α MAP kinase inhibitors are described. These efforts led to the identification of 41 as a potent p38α inhibitor that utilizes a unique nitrogen-sulfur intramolecular nonbonding interaction to stabilize the conformation required for binding to the p38α active site. X-ray crystallographic studies that confirm the proposed binding mode of this class of inhibitors in p38 α and provide evidence for the proposed intramolecular nitrogen-sulfur interaction are discussed.
authors: Department of Immunology Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA.
authors: Shuqun
authors: S
authors: Lin
authors: Stephen T
authors: ST
authors: Wrobleski
authors: John
authors: J
authors: Hynes
authors: Sidney
authors: S
authors: Pitt
authors: Rosemary
authors: R
authors: Zhang
authors: Yi
authors: Y
authors: Fan
authors: Arthur M
authors: AM
authors: Doweyko
authors: Kevin F
authors: KF
authors: Kish
authors: John S
authors: JS
authors: Sack
authors: Mary F
authors: MF
authors: Malley
authors: Susan E
authors: SE
authors: Kiefer
authors: John A
authors: JA
authors: Newitt
authors: Murray
authors: M
authors: McKinnon
authors: James
authors: J
authors: Trzaskos
authors: Joel C
authors: JC
authors: Barrish
authors: John H
authors: JH
authors: Dodd
authors: Gary L
authors: GL
authors: Schieven
authors: Katerina
authors: K
authors: Leftheris
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009584:Nitrogen / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013455:Sulfur / Q000737:chemistry*; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D013455:Sulfur; D048308:Mitogen-Activated Protein Kinase 14; D009584:Nitrogen