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Practical synthesis of a chromene analog for use as a retinoic acid receptor alpha antagonist lead compound.

ABSTRACT: Retinoic acid receptor alpha (RAR?) selective compounds may guide the design of drugs that can be used in conjunction with hormonal adjuvant therapy in the treatment of breast cancer. Herein we report a modified synthesis of a known RAR? antagonist, 2-fluoro-4-[[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)chroman-6-yl]carbonyl]amino]benzoic acid and a synthesis of its unknown, desfluoro analog, 4-[[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)chroman-6-yl]carbonyl]amino]benzoic acid. The modified route allows for facile reaction workups, increased yields, lower cost and incorporates a green alternative step. Structure-activity relationship studies determined through functional cell-based assays, demonstrated antagonism to RAR? for both compounds. Molecular modeling within the RAR? binding pocket was used to compare binding interactions of the desfluoro analog to a known RAR antagonist.

SUBMITTER: Jetson R

PROVIDER: S-EPMC3831886 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Practical synthesis of a chromene analog for use as a retinoic acid receptor alpha antagonist lead compound.

Jetson Rachael R Malik Neha N Luniwal Amarjit A Chari Venkatesh V Ratnam Manohar M Erhardt Paul P

European journal of medicinal chemistry 20130219

Retinoic acid receptor alpha (RARα) selective compounds may guide the design of drugs that can be used in conjunction with hormonal adjuvant therapy in the treatment of breast cancer. Herein we report a modified synthesis of a known RARα antagonist, 2-fluoro-4-[[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)chroman-6-yl]carbonyl]amino]benzoic acid and a synthesis of its unknown, desfluoro analog, 4-[[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)chroman-6-yl]carbonyl]amino]benzoic acid. The modified route a ...[more]

PMID: 23474897

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