264272-64-2Relevant articles and documents
INHIBITORS OF ALPHA 2 BETA 1 INTEGRIN AND METHODS OF USE THEREOF
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Paragraph 0724; 0781-0783; 1541-1543, (2021/11/06)
Disclosed herein, inter alia, are inhibitors of alpha 2 beta 1 integrin and methods of using the same.
Lead optimization of a 4-aminopyridine benzamide scaffold to identify potent, selective, and orally bioavailable TYK2 inhibitors
Liang, Jun,Van Abbema, Anne,Balazs, Mercedesz,Barrett, Kathy,Berezhkovsky, Leo,Blair, Wade,Chang, Christine,Delarosa, Donnie,Devoss, Jason,Driscoll, Jim,Eigenbrot, Charles,Ghilardi, Nico,Gibbons, Paul,Halladay, Jason,Johnson, Adam,Kohli, Pawan Bir,Lai, Yingjie,Liu, Yanzhou,Lyssikatos, Joseph,Mantik, Priscilla,Menghrajani, Kapil,Murray, Jeremy,Peng, Ivan,Sambrone, Amy,Shia, Steven,Shin, Young,Smith, Jan,Sohn, Sue,Tsui, Vickie,Ultsch, Mark,Wu, Lawren C.,Xiao, Yisong,Yang, Wenqian,Young, Judy,Zhang, Birong,Zhu, Bing-Yan,Magnuson, Steven
, p. 4521 - 4536 (2013/07/25)
Herein we report our lead optimization effort to identify potent, selective, and orally bioavailable TYK2 inhibitors, starting with lead molecule 3. We used structure-based design to discover 2,6-dichloro-4-cyanophenyl and (1R,2R)-2-fluorocyclopropylamide modifications, each of which exhibited improved TYK2 potency and JAK1 and JAK2 selectivity relative to 3. Further optimization eventually led to compound 37 that showed good TYK2 enzyme and interleukin-12 (IL-12) cell potency, as well as acceptable cellular JAK1 and JAK2 selectivity and excellent oral exposure in mice. When tested in a mouse IL-12 PK/PD model, compound 37 showed statistically significant knockdown of cytokine interferon-γ (IFNγ), suggesting that selective inhibition of TYK2 kinase activity might be sufficient to block the IL-12 pathway in vivo.
JANUS KINASE INHIBITOR COMPOUNDS AND METHODS
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Page/Page column 101, (2010/12/29)
The invention provides compounds of Formula I, stereoisomers or pharmaceutically acceptable salts thereof, wherein A, B, D, R1, R2, R4 and R5 are defined herein, a pharmaceutical composition that includes a compound of Formula I and methods of use thereof