7421. Pifithrin-α

Nomenclature

CAS number: 63208-82-2
1-(4-Methylphenyl)-2-(4,5,6,7-tetrahydro-2-imino-3(2H)-benzothiazolyl)ethanone monohydrobromide; 2-(2-imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone hydrobromide; PFT-α.
C16H18N2OS.HBr; mol wt 367.30.
C 52.32%, H 5.21%, N 7.63%, O 4.36%, S 8.73%, Br 21.75%.

Description and references

Small molecule inhibitor of p53-mediated gene activation and apoptosis; the name pifithrin is an abbreviation for p-fifty three inhibitor. Converted in vitro to the planar tricyclic condensation product, pifithrin-β. Prepn: A. Singh et al., Indian J. Chem. 14B, 997 (1976). Identification of p53 inhibition: P. G. Komarov et al., Science 285, 1733 (1999). Synthesis and neuroprotective activity: X. Zhu et al., J. Med. Chem. 45, 5090 (2002). Inhibition of heat shock and glucocorticoid signal transduction pathways: E. A. Komarova et al., J. Biol. Chem. 278, 15465 (2003). Characterization as an aryl hydrocarbon receptor agonist: M. S. Hoagland et al., J. Pharmacol. Exp. Ther. 314, 603 (2005). Conversion to pifithrin-β: R. K. Gary, D. A. Jensen, Mol. Pharm. 2, 462 (2005).

Chemical structure

Properties

mp 182°. pKa 9.11. Sol in water, DMSO.

Derivative

Pifithrin-β.

Nomenclature

CAS number: 60477-34-1; 511296-88-1 (hydrobromide)
5,6,7,8-Tetrahydro-2-(4-methylphenyl)imidazo[2,1-b]benzothiazole; 2-(4-methylphenyl)imidazo[2,1b]-5,6,7,8-tetrahydrobenzothiazole; 2-p-tolyl-5,6,7,8-tetrahydrobenzo[d]imidazo[2,1-b]thiazole; cyclic pifithrin-α.
C16H16N2S; mol wt 268.38.
C 71.60%, H 6.01%, N 10.44%, S 11.95%.

Description and references

Crystal structure: W. Clegg, C. Jamieson, Acta Crystallogr. E61, o1486 (2005).

Properties

Crystals from methanol. mp 185°. pKa 4.36. Log P (octanol/water): 4.26. Crystal density: 1.318 Mg/m3.

Use

Biochemical tool in studies of p53 function and apoptosis.