1691250-97-1Relevant articles and documents
Discovery and Biological Evaluation of N-Methyl-pyrrolo[2,3- b]pyridine-5-carboxamide Derivatives as JAK1-Selective Inhibitors
Park, Eunsun,Lee, Sun Joo,Moon, Heegyum,Park, Jongmi,Jeon, Hyeonho,Hwang, Ji Sun,Hwang, Hayoung,Hong, Ki Bum,Han, Seung-Hee,Choi, Sun,Kang, Soosung
, p. 958 - 979 (2021/02/01)
Janus kinase 1 (JAK1) plays a key role in most cytokine-mediated inflammatory and autoimmune responses through JAK/STAT signaling; thus, JAK1 inhibition is a promising therapeutic strategy for several diseases. Analysis of the binding modes of current JAK inhibitors to JAK isoforms allowed the design of N-alkyl-substituted 1-H-pyrrolo[2,3-b] pyridine carboxamide as a JAK1-selective scaffold, and the synthesis of various methyl amide derivatives provided 4-((cis-1-(4-chlorobenzyl)-2-methylpiperidin-4-yl)amino)-N-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxamide (31g) as a potent JAK1-selective inhibitor. In particular, the (S,S)-enantiomer of 31g (38a) exhibited excellent potency for JAK1 and selectivity over JAK2, JAK3, and TYK2. On investigating the effect of 31g on hepatic fibrosis, it was found that it reduces the proliferation and fibrogenic gene expression of TGF-β-induced hepatic stellate cells (HSCs). Specifically, 31g significantly inhibited TGF-β-induced migration of HSCs at 0.25 μM in wound-healing assays.
CARM1 INHIBITORS AND USES THEREOF
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, (2016/04/09)
Provided herein are compounds of Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein X, R1, R1a, R2a, R2b, R2c, R2d, are as defined herein, and Ring HET is a 6-membered monocyclic heteroaryl ring system of Formula: wherein L2, R13, G8, G10, G11, and G12 are as defined herein. Compounds of the present invention are useful for inhibiting CARMl activity. Methods of using the compounds for treating CARMl -mediated disorders are also described.
TRPA1 MODULATORS
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Paragraph 0550, (2015/07/16)
This disclosure relates to polycyclic heteroaromatic compounds useful as TRPA1 modulators, as well as compositions and methods of treating pain that include the compounds.