The structure-activity relationships of (E)-chalcone-4-carboxylic
acids, which are retinoidal
benzoic acids represented by R-Ph-X-Ph-COOH (4, X = -COCH = CH-), are discussed on the basis of differentiation-inducing activity on human promyelocytic
leukemia cells HL-60. The activity was increased by the substitution of a bulky alkyl group(s) (R), and among such compounds, (E)-4-[3-(3,5-di-tert-butylphenyl)-3-oxo-1-propenyl]
benzoic acid (
Ch55) and (E)-4-[3-oxo-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1 -propenyl]
benzoic acid (Ch80) are several times more active than
retinoic acid. Though the stable conformer of
chalcone derivatives is linear (s-cis form), the conformationally restricted analogue 4-(6,7,8,9-tetrahydro-6,6,9,9-tetramethyl-4H-4-oxonaphtho[2,3-b]py
ran-2-yl)
benzoic acid (Fv80) is more active than Ch80. While the effect of introduction of an
oxygen atom varied, 4-[1-hydroxy-3-oxo-3-(5,6,7,8-tetrahydro-3-hydroxy-5,5,8,8-tetramethyl-2 - naphthalenyl)-1-propenyl]
benzoic acid (Re80), regarded as a derivative of Ch80 with two additional
hydroxyl groups, has very strong activity.