Discovery of a novel series of quinoxalines as inhibitors of c-Met kinase

Pharmacophore modeling and virtual screening studies to identify new c-Met inhibitors

“…It had the lowest total cost (94.962), the least difference between total and fixed cost (11.972), the highest cost difference between null cost and total cost (154.252), the least RMSD (0.756), and a strong correlation coefficient (0.983) between experimental and estimated activities. And the configuration cost of Hypo1 was 15.095, which did not exceed the maximum limit value of 17 and could guarantee the entire conformation space sampled during the pharmacophore generation. One method of judging a pharmacophore's merit is its ability to predict the activities of individual compounds in the training set [23][24][25].…”

“…At last, 23 structurally diverse compounds with activity values (IC 50 ) between 3 nM and 28,300 nM were selected as training set ( Fig. 2) [3,6,[13][14][15][16][17][18][19], which spanned over four magnitudes. There are ten diverse scaffolds in the training set, including azaindoles, benzyloxyquinolines, quinoxalines, pyridins and other relevant structures.…”

Present status of quinoxaline motifs: Excellent pathfinders in therapeutic medicine

“…Other reported quinoxaline scaffolds with improved kinase inhibitory activity were 188 [173], 189 [174], 190 [175], 191 [176], 192 [176] and 193 [177]. <<<<Fig.…”

Enhancing the cellular anti-proliferation activity of pyridazinones as c-met inhibitors using docking analysis

“…Utilizing a structure-based drug design approach [8], a number of small molecules bearing various pharmacophoric scaffolds, including triazolopyridazines [9], triazolotriazines [10], quinolones [11e16], pyridines and fused pyridines [17e22] pyrimidines [23e25], indolines/indoles [26], dioxopyrazolidines [27], and quinoxalines [28], have been found to be c-Met inhibitors. Several of these substances are now in clinical trials and two of them (1 and 3) were approved by the FDA (Fig.…”