7546-50-1

Usage

InChI:InChI=1/C10H10N2O2/c1-6-8(5-9(13)14)7-3-2-4-11-10(7)12-6/h2-4H,5H2,1H3,(H,11,12)(H,13,14)

Upstream product

• 23612-48-8 2-methyl-1H-pyrrolo[2,3-b]pyridine 

Downstream Products

• 872365-14-5 2-[2-methyl-1-[[4-methylsulfonyl-2-(trifluoromethyl)phenyl]methyl]pyrrolo[2,3-b]pyridine-3-yl]acetic acid 

Relevant academic research and scientific papers

Design, synthesis, and spectroscopic study of 7-azaindolyl hydrazones with anti-breast cancer activity

A series of 7-azaindolyl hydrazones were prepared by reacting of hydrazides of 7-azaindole-3-acetic acids with aromatic aldehydes and N-substituted indolyl-3-carboxyaldehydes. Structure of all the synthesized compounds were satisfactorily correlated by IR, 1H NMR, 13C NMR and mass spectroscopic evidences. The synthesized compounds were evaluated for their possible anticancer potential against MCF-7 induced breast carcinoma. It is worth mentioning that most of the compounds were considerably active against MCF-7 cell line with GI50 values ranging from 22.3–81.0 μM. The hydrazones of N-1-substituted indole-3-carboxyaldehydes 9f, 9g, 9h, 9c, and 9j were active against MCF-7 cell line with GI50 values less than 40 μM (GI50 = 22.3 and 24.9, 29.6, 30.2 and 37.8 μM respectively) with moderate TGI values (TGI = 56.6, 59.5, 65.5, 70.7 and 94.6 μM respectively). The active compounds were also screened against the normal Vero monkey cell line, which showed moderate selectivity against inhibition of cancer cells.

Fevipiprant selective prostaglandin DP2 (CRTh2) inhibitor treatment of asthma

Prostaglandin D2 (PGD2), a major prostanoid, releases from activated mast cells. It activates and recruits various inflammatory cells like eosinophils and basophils through DP2 receptors to the site of inflammation and further promotes late-phase allergic reactions. For the last decade, the scientific community has extensively explored this pathway and synthesized various specific DP2 receptor antagonists for the management of asthma. About 20 compounds with DP2 antagonistic activity have reached different stages of clinical development. Among these, fevipiprant is one of the most advanced oral DP2 inhibitors as it selectively blocks the DP2 receptors. Fevipiprant has demonstrated an acceptable safety profile in phase II studies as evident from significant reduction of moderate to severe asthma exacerbations. Currently this novel antiasthmatic drug is in phase III clinical trials. This review provides a brief overview of PGD2 blockers, particularly fevipiprant and its preclinical pharmacology and clinical development, by providing a summary of completed or ongoing clinical studies assessing its safety and efficacy in asthma.

Depsipeptides Featuring a Neutral P1 Are Potent Inhibitors of Kallikrein-Related Peptidase 6 with On-Target Cellular Activity

Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease that belongs to the family of tissue kallikreins (KLKs). Many KLKs are investigated as potential biomarkers for cancer as well as therapeutic drug targets for a number of pathologies. KLK6, in particular, has been implicated in neurodegenerative diseases and cancer, but target validation has been hampered by a lack of selective inhibitors. This work introduces a class of depsipeptidic KLK6 inhibitors, discovered via high-throughput screening, which were found to function as substrate mimics that transiently acylate the catalytic serine of KLK6. Detailed structure-activity relationship studies, aided by in silico modeling, uncovered strict structural requirements for potency, stability, and acyl-enzyme complex half-life. An optimized scaffold, DKFZ-251, demonstrated good selectivity for KLK6 compared to other KLKs, and on-target activity in a cellular assay. Moreover, DKFZ-633, an inhibitor-derived activity-based probe, could be used to pull down active endogenous KLK6.