title: Potency switch between CHK1 and MK2: discovery of imidazo[1,2-a]pyrazine- and imidazo[1,2-c]pyrimidine-based kinase inhibitors.
abstract: Chemistry has been developed to access both imidazo[1,2-a]pyrazines and imidazo[1,2-c]pyrimidines. Small structural modifications in both series led to a switch of potency between two kinases involved in mediating cell cycle checkpoint control, CHK1 and MK2.
authors.affiliation: Merck Research Laboratories, 320 Bent Street, Cambridge, MA 02141, USA. zhaoyang.meng@merck.com
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Meng
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Ciavarri
authors.forename: Andrew
authors.initials: A
authors.lastname: McRiner
authors.forename: Yinyan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Lianyun
authors.initials: L
authors.lastname: Zhao
authors.forename: Panduranga Adulla
authors.initials: PA
authors.lastname: Reddy
authors.forename: Xingmin
authors.initials: X
authors.lastname: Zhang
authors.forename: Thierry O
authors.initials: TO
authors.lastname: Fischmann
authors.forename: Charles
authors.initials: C
authors.lastname: Whitehurst
authors.forename: M
authors.initials: M
authors.lastname: Arshad Siddiqui
mesh_terms: D000071877:Checkpoint Kinase 1; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D000071877:Checkpoint Kinase 1; D007093:Imidazoles; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011719:Pyrazines; D011743:Pyrimidines; D000099190:MAP-Kinase-Activated Kinase 2; C556838:imidazo(1,2-a)pyrazine; C584266:imidazo(1,2-c)pyrimidine; C000605867:CHEK1 protein, human