Design and Synthesis of Novel N‐(2‐aminophenyl)benzamide Derivatives as Histone Deacetylase Inhibitors and Their Antitumor Activity Study

Abstract

Histone deacetylases (HDACs) are promising therapeutic targets for cancer therapy because inhibition of HDACs triggers growth arrest or apoptosis of tumor cells. In the present study, a new series of fluorinated N-(2-aminophenyl)benzamide derivatives were synthesized to investigate potential inhibition of HDACs and associated anticancer activity. Among the synthesized derivatives, compound 24a showed potent inhibitory activity of HDACs and higher antitumor efficacy in human cancer cell lines (HCT-116, MCF-7, and A549) compared with SAHA. Moreover, animal studies demonstrated that compound 24a showed potent in vivo antitumor efficacy in an HCT-116 colon cancer xenograft mouse model.

Development and Biological Evaluation of the First Highly Potent and Specific Benzamide-Based Radiotracer [18F]BA3 for Imaging of Histone Deacetylases 1 and 2 in Brain

“…1 H-NMR (400 MHz, CDCl 3 ) δ 9.65 (s, 1H), 8.59 (d, J = 9.0 Hz, 1H), 8.40 (d, J = 2.3 Hz, 1H), 7.82 (dd, J = 8.9, 2.3 Hz, 1H), 7.37–7.30 (m, 2H), 7.10 (dd, J = 5.1, 3.6 Hz, 1H), 1.56 (s, 9H); 13 C-NMR (101 MHz, CDCl 3 ) δ 152.27, 141.49, 136.20, 134.96, 133.07, 128.88, 128.46, 125.81, 124.08, 122.52, 121.35, 82.17, 28.36 (in accordance with literature [ 53 ]).…”

“…1 H-NMR (400 MHz, CDCl 3 ) δ 9.60 (s, 1H), 8.51 (d, J = 9.2 Hz, 1H), 8.33 (d, J = 2.4 Hz, 1H), 7.68 (dd, J = 9.2, 2.4 Hz, 1H), 1.54 (s, 9H); 13 C-NMR (101 MHz, CDCl 3 ) δ 152.09, 138.67, 136.32, 135.28, 128.40, 122.35, 113.88, 82.45, 28.32 (in accordance with literature [ 53 ]).…”

“…Hz, 1H), 7.68 (dd, J = 9.2, 2.4 Hz, 1H), 1.54 (s, 9H);13 C-NMR (101 MHz, CDCl 3 ) δ 152.09, 138.67, 136.32, 135.28, 128.40, 122.35, 113.88, 82.45, 28.32 (in accordance with literature[53]). 3.3.2.…”

“…First of all, the amino group was treated with di-tert-butyl dicarbonate (Boc 2 O) and catalytic amounts of N,N-dimethyl-4-aminopyridine (DMAP) to afford the bis-Boc-protected intermediate followed by cleavage of one Boc group using trifluoroacetic acid (TFA) to give tert-butyl (4-bromo-2-nitrophenyl)carbamate (1) in a total yield of 95%. Under these conditions it was possible to achieve higher yields with this two-step synthesis compared with the reported yields [49][50][51][52][53] using a one-step synthesis. Subsequently, 1 was reacted with 2-/3-thienyl-, 2-/3-furanyl-or para-fluoro-phenylboronic acid in a Suzuki cross coupling reaction with tetrakis(triphenylphosphine)palladium(0) (Pd(PPh 3 ) 4 ) in 1,4-dioxane/water (7:3, v/v) to provide the corresponding compounds 2a-e in very good yields (90-96%).…”

SIWV tetrapeptide and ROS-responsive prodrug conjugate for advanced glioblastoma therapy

“…16,17 The development of a conjugated formulation of drugs with a receptor-targeting moiety (peptides, small molecules, proteins) is a representative method. 18,19…”