10034. Vorinostat

Nomenclature

CAS number: 149647-78-9
N1-Hydroxy-N8-phenyloctanediamide; suberoylanilide hydroxamic acid; SAHA; Zolinza (Merck & Co.).
C14H20N2O3; mol wt 264.32.
C 63.62%, H 7.63%, N 10.60%, O 18.16%.

Description and references

Second generation hybrid polar compound. Histone deacetylase (HDAC) inhibitor that induces cell cycle arrest, differentiation and apoptosis in tumor cells. Prepn: R. Breslow et al., WO 9307148; eidem, US 5369108 (1993, 1994 both to Sloan-Kettering Inst.; Columbia Univ.); J. C. Stowell et al., J. Med. Chem. 38, 1411 (1995). Improved synthesis: A. Mai et al., Org. Prep. Proced. Int. 33, 391 (2001). HTLC determn in serum: L. Du et al., Rapid Commun. Mass Spectrom. 19, 1779 (2005). Clinical pharmacokinetics and activity in cancer patients: W. K. Kelly et al., J. Clin. Oncol. 23, 3923 (2005). Clinical trial in cutaneous T-cell lymphoma: E. A. Olsen et al., J. Clin. Oncol. 25, 3109 (2007). Review of mechanism of action: V. M. Richon et al., Blood Cells Mol. Dis. 27, 260-264 (2001); and clinical experience: P. A. Marks, Oncogene 26, 1351-1356 (2007).

Chemical structure

Properties

White to light orange powder. Crystals from acetonitrile, mp 159-160.5°. pKa 9.2. Freely sol in DMSO; slightly sol in ethanol, isopropanol, acetone; very slightly sol in water. Insol in methylene chloride. pH of saturated soln in water: 6.6.

Therapeutic Category

Antineoplastic.

Keywords

Antineoplastic; Histone Deacetylase Inhibitors