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
, 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.
