331652-44-9Relevant academic research and scientific papers
Development of a novel class of B-RafV600E-selective inhibitors through virtual screening and hierarchical hit optimization
Kong, Xiangqian,Qin, Jie,Li, Zeng,Vultur, Adina,Tong, Linjiang,Feng, Enguang,Rajan, Geena,Liu, Shien,Lu, Junyan,Liang, Zhongjie,Zheng, Mingyue,Zhu, Weiliang,Jiang, Hualiang,Herlyn, Meenhard,Liu, Hong,Marmorstein, Ronen,Luo, Cheng
experimental part, p. 7402 - 7417 (2012/10/08)
Oncogenic mutations in critical nodes of cellular signaling pathways have been associated with tumorigenesis and progression. The B-Raf protein kinase, a key hub in the canonical MAPK signaling cascade, is mutated in a broad range of human cancers and especially in malignant melanoma. The most prevalent B-RafV600E mutant exhibits elevated kinase activity and results in constitutive activation of the MAPK pathway, thus making it a promising drug target for cancer therapy. Herein, we describe the development of novel B-RafV600E selective inhibitors via multi-step virtual screening and hierarchical hit optimization. Nine hit compounds with low micromolar IC 50 values were identified as B-RafV600E inhibitors through virtual screening. Subsequent scaffold-based analogue searching and medicinal chemistry efforts significantly improved both the inhibitor potency and oncogene selectivity. In particular, compounds 22f and 22q possess nanomolar IC 50 values with selectivity for B-RafV600Ein vitro and exclusive cytotoxicity against B-RafV600E harboring cancer cells.
Inhibition of gastric H+, K+-ATPase by novel thiazolidinone derivatives
Chandrappa,Vinaya,Srikanta,Ananda Kumar,Prasanna,Thimmegowda,Dharmesh, Shylaja M.,Rangappa
experimental part, p. 189 - 196 (2010/11/18)
In a program to identify new anti-ulcer compounds, a series of novel substituted thiazolidinone derivatives 5(a-j) were synthesized and screened for their in vitro H+, K+-ATPase inhibitory activity. The synthesized compounds were characterized by nuclear magnetic resonance ( 1H-NMR), liquid chromatography-mass spectrometry (LCMS) and fourier transform infrared (FTIR) analysis. We have briefly investigated the structure-activity relation (SAR) studies and reveal that the nature of position of the fluorine atom influences the anti-ulcer activity. Among the synthesized compounds 5b, 5c and 5e showed 4 and 10-fold higher H+, K +-ATPase activity when compared with those of other derivatives 5a, 5f, 5g and 5j, respectively. H+, K+-ATPase activity of 5b, 5c and 5e were comparable with those of known H+, K +-ATPase blocker lansoprazole which is a potential anti-ulcer drug.
