FLUORINATED RETINOIC ACIDS AND THEIR ANALOGS .1. SYNTHESIS AND BIOLOGICAL-ACTIVITY OF (4-METHOXY-2,3,6-TRIMETHYLPHENYL)NONATETRAENOIC ACID ANALOGS

(4-Methoxy-2, 3, 6-trimethylphenyl)nonatetraenoic acids, esters, and amides (analogues of retinoic acid) bearing a fluorine atom(s) or a trifluoromethyl group on the polyene side chain were synthesized. The biological activities of these compounds and of 10-, 12-, and 14-fluororetinoic acid esters were evaluated in vivo in a chemically induced mouse papilloma test; the toxicities were assessed in an in vivo mouse hypervitaminosis A test. Antipapilloma activity greater than the parent nonfluorinated ester was found for lc (ethyl 12-fluororetinoate) and 23 and 39 (aromatic 4-and 6-fluororetinoid esters, respectively). A similar increase in antipapilloma activity was observed for 71 and 72, the aromatic 4-and 6-iluororetinoic acids, respectively, relative to 2 and for 73 (aromatic 4-fluororetinoid amide) relative to 4. © 1979, American Chemical Society. All rights reserved.