Tazarotene, receptor-selective retinoid

Chandraratna RAS (1996) Tazarotene first of a new generation of receptor-selective retinoids. Br J Dermatol 135 18-25... 

The major approach for synthesis of retinoids of the tetraenoic acids involves the Wittig-Homer-Emmons reaction. The photochemical reaction has also proved viable and conditions to perform this reaction on commercial scale have been identified. Identification of receptor selective retinoids expanded the chemistry of file retinoids to aryl (Bexarotene, Adapalene) and heteroaryl (Tazarotene) platforms. These analogs are prepared rapidly and efficiently and this chemistry should facilitate both the SAR and commercial development of more novel and selective members of the retinoid class. 

Systemically administered retinoids such as isotretinoin (1, Accutane ) have several disadvantages such as a relatively narrow therapeutic index and a variety of toxic effects including teratogenicity. Topically administered retinoids may avoid some of those drawbacks. For instance, tazarotene (2, Tazorac ) is a topical receptor-selective retenoid that normalizes differentiation and proliferation of keratinocytes. Its major metabolite, tazarotenic acid (11), binds to retinoic acid receptors (RARs) with high affinity. 

Chandraratna RA. Tazarotene the first receptor-selective topical retinoid for the treatment of psoriasis. J Am Acad Dermatol 1997 37 S12-S17. 

Like other retinoids, tazarotene (Razorac) acts by binding to RARs and altering gene expression. Tazarotene appears to be particularly selective for the retinoid receptors RAR-(3 and RAR-y,but the clinical significance of this observation is unknown. 

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