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.
SMYD INHIBITORS
-
Paragraph 0910; 0913-0915, (2017/07/18)
The present disclosure provides carboxamides and sulfonamides having Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein A, Y, B, X, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.
CARM1 INHIBITORS AND USES THEREOF
-
, (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.
SUBSTITUTED PIPERIDINE COMPOUNDS
-
Paragraph 0273, (2016/06/01)
The present disclosure provides substituted piperidine compounds having Formula (I), and the pharmaceutically acceptable salts and solvates thereof, wherein R1, B, X, and Z are defined as set forth in the specification. The present disclosure i
TRPA1 MODULATORS
-
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.
COMPOUNDS WHICH HAVE ACTIVITY AT M1 RECEPTOR AND THEIR USES IN MEDICINE
-
Page/Page column 50, (2008/12/04)
Compounds of formula (I) or a salt thereof are provided: (I) wherein R4, R5, R6, Q and R are as defined in the description. Uses of the compounds as medicaments and in the manufacture of medicaments for treating psychotic
