Talarozole

Talarozole
Clinical data
Routes of; administration	oral, topical
ATC code	none;
Identifiers
	IUPAC name N-(2-Benzothioazolyl)-N-[4-[2-ethyl-1-(1,2,4-triazo-1-yl)butyl]phenyl]amine;
CAS Number	201410-53-9 ;
PubChem CID	9799888;
ChemSpider	7975653 ;
UNII	XKD9N5CJ6W;
ChEBI	CHEBI:101854 ;
Chemical and physical data
Formula	C21H23N5S
Molar mass	377.505 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES c2ncnn2C(C(CC)CC)c(cc3)ccc3Nc4nc1ccccc1s4;
	InChI InChI=1S/C21H23N5S/c1-3-15(4-2)20(26-14-22-13-23-26)16-9-11-17(12-10-16)24-21-25-18-7-5-6-8-19(18)27-21/h5-15,20H,3-4H2,1-2H3,(H,24,25) ; Key:SNFYYXUGUBUECJ-UHFFFAOYSA-N ;
(what is this?) (verify)

Talarozole (formerly R115866, planned trade name Rambazole) was an investigational drug for the treatment of acne, psoriasis and other keratinization disorders. Development has been discontinued.[1]

Talarozole inhibits the metabolism of retinoic acid by blocking cytochrome P450 enzyme CYP26 isoenzymes (CYP26A1 and possibly also CYP26B1), retinoic acid hydroxylases.[2] Because of this mechanism, it is called a retinoic acid metabolism blocking agent (RAMBA).[2][3]

It has 750-fold higher potency than the earlier drug liarozole as well as greater selectivity, with more than 300-fold selectivity for inhibition of CYP26A1 over other steroid-metabolizing enzymes like CYP17A1 (17α-hydroxylase/17,20-lyase) and aromatase (CYP19A1).[2][4]

References

http://adisinsight.springer.com/drugs/800020802
Nelson CH, Buttrick BR, Isoherranen N (2013). "Therapeutic potential of the inhibition of the retinoic acid hydroxylases CYP26A1 and CYP26B1 by xenobiotics". Curr Top Med Chem. 13 (12): 1402–28. doi:10.2174/1568026611313120004. PMC 4366427. PMID 23688132.
Giltaire, S; Herphelin F; Frankart A; Hérin M; Stoppie P; Poumay Y (11 December 2008). "The CYP26 inhibitor R115866 potentiates the effects of all-trans retinoic acid on cultured human epidermal keratinocytes". Br J Dermatol. 160 (3): 505–13. doi:10.1111/j.1365-2133.2008.08960.x. PMID 19120344.
Gomaa MS, Lim AS, Lau SC, Watts AM, Illingworth NA, Bridgens CE, Veal GJ, Redfern CP, Brancale A, Armstrong JL, Simons C (2012). "Synthesis and CYP26A1 inhibitory activity of novel methyl 3-[4-(arylamino)phenyl]-3-(azole)-2,2-dimethylpropanoates". Bioorg. Med. Chem. 20 (20): 6080–8. doi:10.1016/j.bmc.2012.08.044. PMID 22989911.

External links

Talarozole - AdisInsight

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[AdisInsight-1] ttp://adisinsight.springer.com/drugs/800020802

[pmid23688132-2] Nelson CH, Buttrick BR, Isoherranen N (2013). "Therapeutic potential of the inhibition of the retinoic acid hydroxylases CYP26A1 and CYP26B1 by xenobiotics". Curr Top Med Chem. 13 (12): 1402–28. doi:10.2174/1568026611313120004. PMC 4366427. PMID 23688132.

[pmid19120344-3] Giltaire, S; Herphelin F; Frankart A; Hérin M; Stoppie P; Poumay Y (11 December 2008). "The CYP26 inhibitor R115866 potentiates the effects of all-trans retinoic acid on cultured human epidermal keratinocytes". Br J Dermatol. 160 (3): 505–13. doi:10.1111/j.1365-2133.2008.08960.x. PMID 19120344.

[pmid22989911-4] Gomaa MS, Lim AS, Lau SC, Watts AM, Illingworth NA, Bridgens CE, Veal GJ, Redfern CP, Brancale A, Armstrong JL, Simons C (2012). "Synthesis and CYP26A1 inhibitory activity of novel methyl 3-[4-(arylamino)phenyl]-3-(azole)-2,2-dimethylpropanoates". Bioorg. Med. Chem. 20 (20): 6080–8. doi:10.1016/j.bmc.2012.08.044. PMID 22989911.