Deng, Jing; Feng, Enguang; Ma, Sheng; Zhang, Yan; Liu, Xiaofeng; Li, Honglin; Huang, Huang; Zhu, Jin; Zhu, Weiliang; Shen, Xu; Miao, Liyan; Liu, Hong; Jiang, Hualiang; Li, Jian published the artcile< Design and synthesis of small molecule RhoA inhibitors: a new promising therapy for cardiovascular diseases?>, Category: quinoxaline, the main research area is quinoxaline derivative preparation SAR drug screen RhoA inhibitory; cardiovascular disease.
RhoA is a member of Rho GTPases, a subgroup of the Ras superfamily of small GTP-binding proteins. RhoA, as an important regulator of diverse cellular signaling pathways, plays significant roles in cytoskeletal organization, transcription, and cell-cycle progression. The RhoA/ROCK inhibitors have emerged as a new promising treatment for cardiovascular diseases. However, to date, RhoA inhibitors are macromols., and to our knowledge, small mol.-based inhibitors have not been reported. In this study, a series of first-in-class small mol. RhoA inhibitors have been discovered by using structure-based virtual screening in conjunction with chem. synthesis and bioassay. Virtual screening of ∼200,000 compounds, followed by SPR-based binding affinity assays resulted in three compounds with binding affinities to RhoA at the micromolar level. Compound I was selected for further structure modifications in considering binding activity and synthesis ease. Forty-one new compounds were designed and synthesized accordingly. It was found that eight showed high RhoA inhibition activities with IC50 values of 1.24 to 3.00 μM. A pharmacol. assay indicated that two compounds II and III demonstrated noticeable vasorelaxation effects against PE-induced contraction in thoracic aorta artery rings and served as good leads for developing more potent cardiovascular agents.
Journal of Medicinal Chemistry published new progress about Amination. 6272-25-9 belongs to class quinoxaline, and the molecular formula is C8H4ClN3O2, Category: quinoxaline.
Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider