6960-46-9Relevant articles and documents
Structure-based discovery of 1H-indole-2-carboxamide derivatives as potent ASK1 inhibitors for potential treatment of ulcerative colitis
Hou, Shaohua,Yang, Xiping,Tong, Yu,Yang, Yuejing,Chen, Quanwei,Wan, Boheng,Wei, Ran,Wang, Yuchen,Zhang, Yanmin,Kong, Bo,Huang, Jianhang,Chen, Yadong,Lu, Tao,Hu, Qinghua,Du, Ding
, (2020/12/29)
Apoptosis signal-regulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase (MAPK) family, is implicated in many human diseases. Here, we describe the structural optimization of hit compound 7 and conduct further structure-activity relationship (SAR) studies that result in the development of compound 19 with a novel indole-2-carboxamide hinge scaffold. Compound 19 displays potent anti-ASK1 kinase activity and stronger inhibitory effect on ASK1 in AP1-HEK293 cells than previously described ASK1 inhibitor GS-4997. Besides improved in vitro activity, compound 19 also exhibits an appropriate in vivo PK profile. In a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis (UC), compound 19 shows significant anti-UC efficacy and markedly attenuates DSS-induced body weight loss, colonic shortening, elevation in disease activity index (DAI) and inflammatory cell infiltration in colon tissues. Mechanistically, compound 19 represses the phosphorylation of ASK1-p38/JNK signaling pathways and suppresses the overexpression of inflammatory cytokines. Together, these findings suggest that ASK1 inhibitors can potentially be used as a therapeutic strategy for UC.
Design, synthesis and biological evaluation of 7-nitro-1H-indole-2- carboxylic acid derivatives as allosteric inhibitors of fructose-1,6- bisphosphatase
Bie, Jianbo,Liu, Shuainan,Zhou, Jie,Xu, Bailing,Shen, Zhufang
, p. 1850 - 1862 (2014/03/21)
A series of novel indole derivatives was synthesized as inhibitors of fructose-1,6-bisphosphatase (FBPase). Extensive structure-activity relationships were conducted and led to a potent FBPase inhibitor 3.9 with an IC50 of 0.99 μM. The binding mode of this series of indoles was predicted using CDOCKER algorithm. The results of this research will shed light on the further design and optimization of novel small molecules as FBPase inhibitors.
Efficient synthesis of 2-ethoxycarbonyl indoles
Sudhakara,Jayadevappa,Mahadevan,Hulikal, Vijaykumar
experimental part, p. 2506 - 2515 (2009/12/06)
An efficient one-pot procedure for the synthesis of 2-ethoxycarbonyl indoles from commercially available materials has been developed. The one-step procedure involves in situ formation of the hydrazones from phenylhydrazine hydrochloride and ethyl pyruvate in the presence of bismuth nitrate followed by Fischer cyclization in polyphosphoric acid and ethanol. This method is efficient and simple.
