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Abstract: A series of N-benzyl-1-heteroaryl-3-(trifluoromethyl)-1H-pyrazole-5-carboxamides targeting co-activator associated arginine methyltransferase 1 (CARM1) have been designed and synthesized. The potency of these inhibitors was influenced by the nature of the heteroaryl fragment with the thiophene analogues being superior to thiazole, pyridine, isoindoline and benzofuran based inhibitors. [Copyright &y& Elsevier]

The design, synthesis, and biological evaluation of N-(2-aminophenyl)-4-[(4-pyridin-3-ylpyrimidin-2-ylamino)methyl]benzamide 8(MGCD0103) is described. Compound 8is an isotype-selective small molecule histone deacetylase (HDAC) inhibitor that selectively inhibits HDACs 1−3 and 11 at submicromolar concentrations in vitro. 8blocks cancer cell proliferation and induces histone acetylation, p21 cip/waf1protein expression, cell-cycle arrest, and apoptosis. 8is orally bioavailable, has significant antitumor activity in vivo, has entered clinical trials, and shows promise as an anticancer drug. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis and biological evaluation of a variety of 4-(heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides and their analogs is described. Some of these compounds were shown to inhibit HDAC1 with IC50 values below the micromolar range, induce hyperacetylation of histones, upregulate expression of the tumor suppressor p21WAF1/Cip1, and inhibit proliferation of human cancer cells. In addition, certain compounds of this class were active in several human tumor xenograft models in vivo. [Copyright &y& Elsevier]