1378039-20-3Relevant academic research and scientific papers
Identification of an imidazopyridine scaffold to generate potent and selective TYK2 inhibitors that demonstrate activity in an in vivo psoriasis model
Liang, Jun,Van Abbema, Anne,Balazs, Mercedesz,Barrett, Kathy,Berezhkovsky, Leo,Blair, Wade S.,Chang, Christine,Delarosa, Donnie,DeVoss, Jason,Driscoll, Jim,Eigenbrot, Charles,Goodacre, Simon,Ghilardi, Nico,MacLeod, Calum,Johnson, Adam,Bir Kohli, Pawan,Lai, Yingjie,Lin, Zhonghua,Mantik, Priscilla,Menghrajani, Kapil,Nguyen, Hieu,Peng, Ivan,Sambrone, Amy,Shia, Steven,Smith, Jan,Sohn, Sue,Tsui, Vickie,Ultsch, Mark,Williams, Karen,Wu, Lawren C.,Yang, Wenqian,Zhang, Birong,Magnuson, Steven
, p. 4370 - 4376 (2017/09/12)
Herein we report identification of an imidazopyridine class of potent and selective TYK2 inhibitors, exemplified by prototype 6, through constraint of the rotatable amide bond connecting the pyridine and aryl rings of compound 1. Further optimization led to generation of compound 30 that potently inhibits the TYK2 enzyme and the IL-23 pathway in cells, exhibits selectivity against cellular JAK2 activity, and has good pharmacokinetic properties. In mice, compound 30 demonstrated dose-dependent reduction of IL-17 production in a PK/PD model as well as in an imiquimod-induced psoriasis model. In this efficacy model, the IL-17 decrease was accompanied by a reduction of ear thickness indicating the potential of TYK2 inhibition as a therapeutic approach for psoriasis patients.
PYRAZOLOPYRIDINES AND PYRAZOLOPYRIDINES AND THEIR USE AS TYK2 INHIBITORS
-
, (2012/06/01)
The invention provides compounds of Formula (I), stereoisomers or pharmaceutically acceptable salts thereof, wherein A, X, R1, R2, R4 and R5 are defined herein, a pharmaceutical composition that includes a compound of Formula (I) and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of using the compound or composition in therapy, as TYK2 Kinase inhibitors.
