156910-52-0Relevant articles and documents
Assay for identification of compounds that promote melanin production and retinoid-like compounds identified by said assay
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, (2008/06/13)
An in vitro assay for selecting compounds that alter pigmentation of skin is provided. Also, a novel class of pro-pigmentatory compounds is provided which comprise substituted aromatic or heterocyclic carboxylic acids, or derivatives thereof, or pharmaceutically acceptable salts, which do not contain a pheno, naphthol, thiophenol, or a thionaphthol function in free or protected form. In a preferred embodiment, thess compounds will display activity for RXRs. These compounds may be used for altering pigmentation of human skin and/or hair in cosmetic or dermatological compositions, and for the treatment of disorders and disease conditions that affect skin or hair pigmentation.
Synthesis and structure-activity relationships of novel retinoid X receptor-selective retinoids
Boehm,Zhang,Badea,White,Mais,Berger,Suto,Goldman,Heyman
, p. 2930 - 2941 (2007/10/02)
Two series of potent retinoid X receptor (RXR)-selective compounds were designed and synthesized based upon recent observation that (E)-4-[2- (5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1-propenyl]benzoic acid (TTNPB) binds and transactivates only the retinoic acid receptor (RAR) subtypes whereas (E)-4-[2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2- naphthalenyl)-1-propenyl]benzoic acid (3-methyl TTNPB) binds and transactivates both the RAR and RXR subfamilies. Addition of functional groups such as methyl, chloro, bromo, or ethyl to the 3-position of the tetrahydronaphthalene moiety of 4-[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro- 2-naphthyl)carbonyl]benzoic acid (5a) and 4-[1-(5,5,8,8-tetramethyl-5,6,7,8- tetrahydro-2-naphthyl)ethenyl]benzoic acid (6a) results in compounds which elicit potent and selective activation of the RXR class. Such RXR-selective compounds offer pharmacological tools for elucidating the biological role of the individual retinoid receptors with which they interact. Activation profiles in cotransfection and competitive binding assays as well as molecular modeling calculations demonstrate critical structural determinants that confer selectivity for members of the RXR subfamily. The most potent compound of these series, 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2- naphthyl)ethenyl]benzoic acid (6b), is the first RXR-selective retinoid (designated as LGD1069) to enter clinical trials for cancer indications.
