A review of recent investigations in the
retinoid field is presented.
Retinoic acid exerts a prophylactic and a
therapeutic effect on chemically induced benign and
malignant epithelial tumors in mice. In clinical studies positive therapeutic results have been obtained in patients with preneoplastic and neoplastic epithelial lesions. However, treatment with
retinoic acid is limited by serious side effects (
hypervitaminosis A syndrome). Therefore, the synthesis of analogs of
retinoic acid (
retinoids) possessing a more favorable therapeutic ratio has been initiated. Among a large series of synthesized compounds, certain aromatic analogs proved to have a particularly favorable therapeutic ratio. The structure-activity relationship of the most active
retinoids is discussed including some
biological data concerning prophylaxis and
therapy of epithelial
tumors. The total synthesis of
retinoids according to various building schemes is discussed in detail. Methods for the synthesis of the cyclic end group, of the polyene chain component, and of the full
retinoid skeleton are described. Metabolic studies of
retinoic acid and of the most active
retinoid, as well as the synthesis of some isolated metabolites are outlined. Suggestions concerning the mechanism of action of
retinoids are made. Some clinical results on the treatment of
acne,
psoriasis and
precancerous conditions are reported.