Suzuki, Takayoshi; Ota, Yosuke; Ri, Masaki; Bando, Masashige; Gotoh, Aogu; Itoh, Yukihiro; Tsumoto, Hiroki; Tatum, Prima R.; Mizukami, Tamio; Nakagawa, Hidehiko; Iida, Shinsuke; Ueda, Ryuzo; Shirahige, Katsuhiko; Miyata, Naoki published the artcile< Rapid Discovery of Highly Potent and Selective Inhibitors of Histone Deacetylase 8 Using Click Chemistry to Generate Candidate Libraries>, Synthetic Route of 16799-05-6, the main research area is anticancer histone deacetylase 8 inhibitor preparation SAR.
To find HDAC8-selective inhibitors, we designed a library of HDAC inhibitor candidates, each containing a zinc-binding group that coordinates with the active-site zinc ion, linked via a triazole moiety to a capping structure that interacts with residues on the rim of the active site. These compounds were synthesized by using click chem. Screening identified HDAC8-selective inhibitors including (I) (IC50 = 0.070 μM), which was more potent than PCI-34058 (IC50 = 0.31 μM), a known HDAC8 inhibitor. Mol. modeling suggested that the phenylthiomethyl group of I binds to a unique hydrophobic pocket of HDAC8, and the orientation of the phenylthiomethyl and hydroxamate moieties (fixed by the triazole moiety) is important for the potency and selectivity. The inhibitors caused selective acetylation of cohesin in cells and exerted growth-inhibitory effects on T-cell lymphoma and neuroblastoma cells (GI50 = 3-80 μM). These findings suggest that HDAC8-selective inhibitors have potential as anticancer agents.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 16799-05-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BrCl, Synthetic Route of 16799-05-6.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics