Modeling, synthesis, and biological evaluation of potential retinoid X receptor (RXR) selective agonists: novel analogues of 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene) and (E)-3-(3-(1,2,3,4-tetrahydro-1,1,4,4,6-pentamethylnaphthalen-7-yl)-4-hydroxyphenyl)acrylic acid (CD3254).
Peter W Jurutka, Ichiro Kaneko, Joanna Yang, Jaskaran S Bhogal, Johnathon C Swierski, Christa R Tabacaru, Luis A Montano, Chanh C Huynh, Rabia A Jama, Ryan D Mahelona, Joseph T Sarnowski, Lisa M Marcus, Alexis Quezada, Brittney Lemming, Maria A Tedesco, Audra J Fischer, Said A Mohamed, Joseph W Ziller, Ning Ma, Geoffrey M Gray, Arjan van der Vaart, Pamela A Marshall, Carl E Wagner
Three unreported analogues of 4-[1-(3,5,5,8,8-pentamethyl-5-6-7-8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (1), otherwise known as bexarotene, as well as four novel analogues of (E)-3-(3-(1,2,3,4-tetrahydro-1,1,4,4,6-pentamethylnaphthalen-7-yl)-4-hydroxyphenyl)acrylic acid (CD3254), are described and evaluated for their retinoid X receptor (RXR) selective agonism. Compound 1 has FDA approval as a treatment for cutaneous T-cell lymphoma (CTCL), although treatment with 1 can elicit side-effects by disrupting other RXR-heterodimer receptor pathways...
November 14, 2013: Journal of Medicinal Chemistry