The probability of finding retinoids with better therapeutic indices has increased dramatically in the past few years because our understanding of the molecular mechanisms of retinoid action has progressed rapidly since the discovery of the six known retinoid receptors, RARα, RARβ, RARγ, and RXRα, RXRβ, RXRγ It is known that each of the RAR subtypes has a specific tissue distribution pattern (REES 1992). Thus, the full therapeutic potential of retinoids may only be realized if new compounds with vastly improved therapeutic indices can be developed. The use of retinoids in other therapeutic areas is limited because they cause a wide variety of toxic side effects such as teratogenicity and mucocu- taneous toxicity. Currently, retinoids are useful for the treatment of a limited number human diseases, including skin disorders such as acne and psoriasis, and for the treatment of some cancers. Retinoids are known to mediate many different biological processes, including cellular differentiation and proliferation, epithelial homeostasis, immunocompetence, and embryogenesis ( Sporn et al. First, it would be desirable to decrease the toxic side effects associated with retinoid therapy. There are two primary reasons for developing retinoic acid receptor (RAR) subtype-selective agonists and antagonists.
