Amino acid derivatives as histone deacetylase inhibitors

• Published in: Bioorganic & medicinal chemistry 2008, Vol.18 (1), p.34-38
• Main Authors: Hubbs, Jed L., Zhou, Hua, Kral, Astrid M., Fleming, Judith C., Dahlberg, William K., Hughes, Bethany L., Middleton, Richard E., Szewczak, Alexander A., Secrist, J. Paul, Miller, Thomas A.
• Format: Article
• Language: English
• Subjects: Amino acid; Amino Acids - chemical synthesis; Amino Acids - chemistry; Amino Acids - pharmacology; Antineoplastic agents; Benzothiophene; Biological and medical sciences; Cancer; Drug Screening Assays, Antitumor; General aspects; HCT116 Cells; Histone deacetylase; Histone Deacetylase 1; Histone Deacetylase Inhibitors; Humans; Lysine; Medical sciences; Pharmacology. Drug treatments; Piperazines - chemical synthesis; Piperazines - chemistry; Piperazines - pharmacology; Structure-Activity Relationship; Thiophenes - chemical synthesis; Thiophenes - chemistry; Thiophenes - pharmacology; Ugi reaction
• ISSN: 0960-894X; 0968-0896; 1464-3405; 1464-3391
• DOI: 10.1016/j.bmcl.2007.11.017

Ongoing clinical studies indicate that inhibitors of Class I and Class II histone deacetylase (HDAC) enzymes show great promise for the treatment of cancer. Zolinza ® (SAHA, Zolinza ®) was recently approved by the FDA for the treatment of the cutaneous manifestations of cutaneous T-cell lymphoma. As a part of an ongoing effort to identify novel small molecules to target these important enzymes, we have prepared several classes of amino acid-derived HDAC1 inhibitors. The design rationale and in vitro activity against the HDAC1 enzyme and HCT116 cell line are described in this letter.