Design and synthesis of boron containing potential pan-RAR inverse agonists. Academic Article uri icon

Overview

abstract

  • We designed and successfully synthesized the compounds 5 and 8 as potential pan-RAR (retinoic acid receptor) agonists. These two compounds were designed based on an existing pan-RAR agonist (BMS493). We synthesized compound 5, in which the carboxylic acid group in BMS 493 was replaced by boronic ester; and compound 8, in which the double bond of BMS 493 was changed to an oxadiazole (as bioisosteres of double bond) ring. The two target molecules 5 and 8 were synthesized from the commercially available 7-bromo-4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one 1. Compound 1 was derivatized to intermediate 5,5-dimethyl-8-(phenylethynyl)-5,6-dihydronaphthalene-2 carbaldehyde 4 by using alkylation, dehydration, and metal exchange reactions. The intermediate 4 was further converted to 5 by using a Wittig reaction and to 8 by amide coupling and dehydration to give overall 18% and 33% yields, respectively, after 8 steps in each case.

publication date

  • January 3, 2012

Identity

PubMed Central ID

  • PMC3505081

Scopus Document Identifier

  • 84856719284

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0027945

PubMed ID

  • 23180890

Additional Document Info

volume

  • 53

issue

  • 11