title: Conformation constraint of anilides enabling the discovery of tricyclic lactams as potent MK2 non-ATP competitive inhibitors.
abstract: Conformation restriction of linear N-alkylanilide MK2 inhibitors to their E-conformer was developed. This strategy enabled rapid advance in identifying a series of potent non-ATP competitive inhibitors that exhibited cell based activity in anti-TNFα assay.
authors.affiliation: Medicinal Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. dong.xiao@merck.com
authors.forename: Dong
authors.initials: D
authors.lastname: Xiao
authors.forename: Anandan
authors.initials: A
authors.lastname: Palani
authors.forename: Xianhai
authors.initials: X
authors.lastname: Huang
authors.forename: Michael
authors.initials: M
authors.lastname: Sofolarides
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Robert
authors.initials: R
authors.lastname: Aslanian
authors.forename: Zhuyan
authors.initials: Z
authors.lastname: Guo
authors.forename: James
authors.initials: J
authors.lastname: Fossetta
authors.forename: Fang
authors.initials: F
authors.lastname: Tian
authors.forename: Prashant
authors.initials: P
authors.lastname: Trivedi
authors.forename: Peter
authors.initials: P
authors.lastname: Spacciapoli
authors.forename: Charles E
authors.initials: CE
authors.lastname: Whitehurst
authors.forename: Daniel
authors.initials: D
authors.lastname: Lundell
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000813:Anilides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D001667:Binding, Competitive; D004353:Drug Evaluation, Preclinical; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007769:Lactams / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D000255:Adenosine Triphosphate; D000813:Anilides; D047908:Intracellular Signaling Peptides and Proteins; D007769:Lactams; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D000099190:MAP-Kinase-Activated Kinase 2