title: 3-Amino-pyrazolo[3,4-d]pyrimidines as p38α kinase inhibitors: design and development to a highly selective lead.
abstract: Learnings from previous Roche p38-selective inhibitors were applied to a new fragment hit, which was optimized to a potent, exquisitely selective preclinical lead with a good pharmacokinetic profile.
authors.affiliation: Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. michael.soth@roche.com
authors.forename: Michael
authors.initials: M
authors.lastname: Soth
authors.forename: Sarah
authors.initials: S
authors.lastname: Abbot
authors.forename: Allassan
authors.initials: A
authors.lastname: Abubakari
authors.forename: Nidhi
authors.initials: N
authors.lastname: Arora
authors.forename: Humberto
authors.initials: H
authors.lastname: Arzeno
authors.forename: Roland
authors.initials: R
authors.lastname: Billedeau
authors.forename: Nolan
authors.initials: N
authors.lastname: Dewdney
authors.forename: Kieran
authors.initials: K
authors.lastname: Durkin
authors.forename: Sandra
authors.initials: S
authors.lastname: Frauchiger
authors.forename: Manjiri
authors.initials: M
authors.lastname: Ghate
authors.forename: David M
authors.initials: DM
authors.lastname: Goldstein
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Hill
authors.forename: Andreas
authors.initials: A
authors.lastname: Kuglstatter
authors.forename: Fujun
authors.initials: F
authors.lastname: Li
authors.forename: Brad
authors.initials: B
authors.lastname: Loe
authors.forename: Kristen
authors.initials: K
authors.lastname: McCaleb
authors.forename: Joel
authors.initials: J
authors.lastname: McIntosh
authors.forename: Eva
authors.initials: E
authors.lastname: Papp
authors.forename: Jaehyeon
authors.initials: J
authors.lastname: Park
authors.forename: Martin
authors.initials: M
authors.lastname: Stahl
authors.forename: Man-Ling
authors.initials: ML
authors.lastname: Sung
authors.forename: Rebecca
authors.initials: R
authors.lastname: Suttman
authors.forename: David C
authors.initials: DC
authors.lastname: Swinney
authors.forename: Paul
authors.initials: P
authors.lastname: Weller
authors.forename: Brian
authors.initials: B
authors.lastname: Wong
authors.forename: Hasim
authors.initials: H
authors.lastname: Zecic
authors.forename: Tobias
authors.initials: T
authors.lastname: Gabriel
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats
chemical_list: D004791:Enzyme Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D048308:Mitogen-Activated Protein Kinase 14