title: Diamino-1,2,4-triazole derivatives are selective inhibitors of TYK2 and JAK1 over JAK2 and JAK3.
abstract: Tyrosine kinase 2 (TYK2) is required for signaling of interleukin-23 (IL-23), which plays a key role in rheumatoid arthritis. Presented is the design and synthesis of 1,2,4-triazoles, and the evaluation of their inhibitory activity against the Janus associated kinases TYK2 and JAKs 1-3.
authors.affiliation: SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA.
authors.forename: Jeremiah P
authors.initials: JP
authors.lastname: Malerich
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Lam
authors.forename: Barry
authors.initials: B
authors.lastname: Hart
authors.forename: Richard M
authors.initials: RM
authors.lastname: Fine
authors.forename: Boris
authors.initials: B
authors.lastname: Klebansky
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Tanga
authors.forename: Annalisa
authors.initials: A
authors.lastname: D'Andrea
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D053759:Interleukin-23 / Q000378:metabolism; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D053634:TYK2 Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D053759:Interleukin-23; D047428:Protein Kinase Inhibitors; D014230:Triazoles; C045575:1,2,4-triazole; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D053634:TYK2 Kinase