On June 24, 1994, Rewcastle, Gordon W.; Palmer, Brian D.; Dobrusin, Ellen M.; Fry, David W.; Kraker, Alan J.; Denny, William A. published an article.COA of Formula: C7H10N2 The title of the article was Tyrosine Kinase Inhibitors. 3. Structure-Activity Relationships for Inhibition of Protein Tyrosine Kinases by Nuclear-Substituted Derivatives of 2,2′-Dithiobis(1-methyl-N-phenyl-1H-indole-3-carboxamide). And the article contained the following:
A series of indole-substituted 2,2′-dithiobis(1-methyl-N-phenyl-1H-indole-3-carboxamides) I (R = H, 5-Cl, 6-Me, 7-OH, 5-MeO, etc.) were prepared and evaluated for their ability to inhibit the tyrosine kinase activity of both the epidermal growth factor receptor (EGFR) and the nonreceptor pp60v-src tyrosine kinase. The compounds were synthesized by conversion of appropriate 1-methyloxindoles to 1-methyl-2-indolinethiones with P2S5 followed by subsequent reaction with NaH and Ph isocyanate and oxidative dimerization of the resulting 2,3-dihydro-N-phenyl-2-thioxo-1H-indole-3-carboxamides. The parent compound and many of the substituted analogs were moderately potent inhibitors of both kinase enzymes, but no clear relationships were seen between substitution on the indole ring and inhibitory activity. While 4-substituted compounds were generally inactive, 5-substituted derivatives with electron-withdrawing groups showed inhibitory activity. However, none of the substituted compounds showed significantly better activity than the unsubstituted parent compound There was generally a good correlation between activity against the EGFR and pp60v-src kinases, but several compounds did show some specificity (>20-fold) of inhibition; 5-Cl and 5-Br derivatives preferentially inhibited pp60v-src, while the 5-CF3 compound preferentially inhibited EGFR. Selected compounds from the series were found to inhibit the growth of Swiss 3T3 fibroblasts with IC50s in the range 2-25 μM, the most active being 4-substituted derivatives The compounds inhibited bFGF-mediated protein tyrosine phosphorylation in intact cells more effectively than EGFR- or PDGF-mediated phosphorylation. The experimental process involved the reaction of N,3-Dimethylpyridin-2-amine(cas: 156267-13-9).COA of Formula: C7H10N2
The Article related to dithiobismethylphenylindolecarboxamide protein tyrosine kinases inhibitor, indolecarboxamide dithiobismethylphenyl protein tyrosine kinases inhibitor, Heterocyclic Compounds (One Hetero Atom): Indoles, Indolizines, Carbazoles, and Other Arenopyrroles and other aspects.COA of Formula: C7H10N2