title: Discovery of pyrazolo[1,5-a]pyrimidine-based CHK1 inhibitors: a template-based approach--part 1.
abstract: The synthesis and hit-to-lead SAR development of a pyrazolo[1,5-a]pyrimidine hit 4 is described leading to a series of potent, selective CHK1 inhibitors such as compound 17r. In the Letter, the further utility of the pyrazolo[1,5-a]pyrimidine template for the development of potent, selective kinase inhibitors is detailed.
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA. michael.dwyer@merck.com
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dwyer
authors.forename: Kamil
authors.initials: K
authors.lastname: Paruch
authors.forename: Marc
authors.initials: M
authors.lastname: Labroli
authors.forename: Carmen
authors.initials: C
authors.lastname: Alvarez
authors.forename: Kerry M
authors.initials: KM
authors.lastname: Keertikar
authors.forename: Cory
authors.initials: C
authors.lastname: Poker
authors.forename: Randall
authors.initials: R
authors.lastname: Rossman
authors.forename: Thierry O
authors.initials: TO
authors.lastname: Fischmann
authors.forename: Jose S
authors.initials: JS
authors.lastname: Duca
authors.forename: Vincent
authors.initials: V
authors.lastname: Madison
authors.forename: David
authors.initials: D
authors.lastname: Parry
authors.forename: Nicole
authors.initials: N
authors.lastname: Davis
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Seghezzi
authors.forename: Derek
authors.initials: D
authors.lastname: Wiswell
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Guzi
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D000071877:Checkpoint Kinase 1; D018360:Crystallography, X-Ray; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C527752:pyrazolo(1,5-a)pyrimidine; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; D051357:Cyclin-Dependent Kinase 2