13924-94-2Relevant articles and documents
Design, synthesis and biological screening of 2-aminobenzamides as selective HDAC3 inhibitors with promising anticancer effects
Trivedi, Prakruti,Adhikari, Nilanjan,Amin, Sk. Abdul,Jha, Tarun,Ghosh, Balaram
, p. 165 - 181 (2018/09/12)
Histone deacetylases (HDACs) have been found as a potential target for anticancer therapy. A number of HDAC inhibitors have been used pre-clinically and clinically as anticancer agents. In the current study, we have designed and synthesized compound 12a by combining the scaffolds of CI-994 and BG45. Moreover, the structure of compound 12a was optimized and a series of 2-aminobenzamide derivatives were synthesized further. These compounds were tested for their HDAC inhibitory activity and found to be efficient HDAC inhibitors. Compound 26c showed 11.68-fold HDAC3 selectivity over pan HDACs, better than the prototype HDAC3 inhibitor BG45. Most of these compounds exhibited antiproliferative activity in both B16F10 and HeLa cell lines. Particularly, compound 26c exhibited better antitumor efficacy in the cell lines compared to the prototype inhibitors CI-994 and BG45. It was also found to promote apoptosis as well as induced significant cell growth arrest in the G2/M phase of cell cycle in B16F10 melanoma cells. This work may provide significant insight regarding structural information to design newer small molecule HDAC3 inhibitors to fight against the target specific malignancies in future.
Identification of RO4597014, a glucokinase activator studied in the clinic for the treatment of type 2 diabetes
Qian, Yimin,Corbett, Wendy L.,Berthel, Steven J.,Choi, Duk Soon,Dvorozniak, Mark T.,Geng, Wanping,Gillespie, Paul,Guertin, Kevin R.,Haynes, Nancy-Ellen,Kester, Robert F.,Mennona, Francis A.,Moore, David,Racha, Jagdish,Radinov, Roumen,Sarabu, Ramakanth,Scott, Nathan R.,Grimsby, Joseph,Mallalieu, Navita L.
, p. 414 - 418 (2013/07/25)
To resolve the metabolite redox cycling associated with our earlier clinical compound 2, we carried out lead optimization of lead molecule 1. Compound 4 showed improved lipophilic ligand efficiency and demonstrated robust glucose lowering in diet-induced obese mice without a liability in predictive preclinical drug safety studies. Thus, it was selected as a clinical candidate and further studied in type 2 diabetic patients. Clinical data suggests no evidence of metabolite cycling, which is consistent with the preclinical profiling of metabolism.
5,6-BISARYL-2-PYRIDINE-CARBOXAMIDE DERIVATIVES, PREPARATION AND APPLICATION THEREOF IN THERAPEUTICS AS UROTENSIN II RECEPTOR ANTAGONISTS
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Page/Page column 27, (2009/12/28)
The present invention relates to derivatives of 5,6-bisaryl-2-pyridine-carboxamide, their preparation and their application in therapeutics as antagonists of urotensin II receptors.
