Retinobenzoic acids. 3. Structure-activity relationships of retinoidal azobenzene-4-carboxylic acids and stilbene-4-carboxylic acids.
Alkyl-substituted azobenzene-4-carboxylic acids are potent differentiation inducers of human promyelocytic leukemia cell line HL-60 to mature granulocytes. Their structure-activity relationships are very similar to those of other retinoidal benzoic acids which are generally represented by 4 and named retinobenzoic acids. The structure-activity relationships of azobenzenecarboxylic acids can also be applied to the known retinoid TTNPB (3). Thus, (E)-4-[2-(3,4-diisopropylphenyl)-1-propenyl]benzoic acid (St30 (28] and (E)-4-[2-(3-tert-butylphenyl)ethenyl]benzoic acid (St40 (29], the acyclic alkyl analogues of TTNPB, are nearly as active as retinoic acid. Among the oxidatively derived compounds (Az90, Ep series and Ox series) of azobenzene- or stilbenecarboxylic acids, Az90 (71) and Ep80 (61) have strong activities. However, all the bishydroxylated derivatives of TTNPB are inactive, while a diketo analogue Ox580 (69) has only weak potency. The activities of conformationally restricted compounds of TTNPB offer some information on the stereochemistry of the active form of these retinoidal compounds.
Kagechika
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H
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Himi
T
T
Namikawa
K
K
Kawachi
E
E
Hashimoto
Y
Y
Shudo
K
K
D001565:Benzoates / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D008968:Molecular Conformation; D012176:Retinoids / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D001565:Benzoates; D012176:Retinoids; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid