264276-14-4Relevant academic research and scientific papers
HETEROCYCLIC COMPOUNDS AS PROTEIN KINASE INHIBITORS
-
, (2014/06/23)
The present invention provides a heterocyclic compound of formula (I), a pharmaceutically acceptable salt thereof, a prodrug thereof or a hydrate thereof, wherein A, A′ B, D, R1, R2 and R3 are as defined herein, a pharmaceutical composition comprising a compound of formula (I) as an active ingredient, methods of production, and methods of use thereof. Particularly, the present invention provides a compound of formula (I) useful for treating or preventing a disease, condition or disorder associated with protein kinases, preferably Janus Kinase family.
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.
HETEROCYCLIC COMPOUNDS AS PROTEIN KINASE INHIBITORS
-
, (2012/12/13)
The present invention provides a heterocyclic compound of formula (I), a pharmaceutically acceptable salt thereof, a prodrug thereof or a hydrate thereof, wherein A, A' B, D, R1, R2 and R3 are as defined herein, a pharmaceutical composition comprising a compound of formula (I) as an active ingredient, methods of production, and methods of use thereof. Particularly, the present invention provides a compound of formula (I) useful for treating or preventing a disease, condition or disorder associated with protein kinases, preferably Janus Kinase family.
JANUS KINASE INHIBITOR COMPOUNDS AND METHODS
-
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
New phenylalanine derivatives
-
, (2008/06/13)
Specific phenylalanine derivatives or pharmaceutically acceptable. salts thereof have an antagonistic effect on the α4 integrins and, therefore, are usable as therapeutic agents or preventive agents for diseases in which α4 integrin-depending adhesion process participates in the pathology, such as inflammatory diseases, rheumatoid arthritis, inflammatory bowel diseases, systemic lupus erythematosus, multiple sclerosis, Sj?gren's syndrome, asthma, psoriasis, allergy, diabetes, cardiovascular diseases, arterial sclerosis, restenosis, tumor proliferation, tumor metastasis and transplantation rejection.
