192762-71-3

Upstream product

• 4167-73-1 4-(2-hydroxyphenyl)-2-methyl-2-butanol 
• 120-47-8 Ethyl 4-hydroxybenzoate 
• 1740-74-5 1,1-diethoxy-3-methyl-2-butene 
• 192762-70-2 ethyl 8-bromo-2,2-dimethyl-4-oxochroman-6-carboxylate 
• 6630-24-6 ethyl 2,2-dimethylchromene-6-carboxylate 
• 32333-31-6 2,2-dimethyl-6-acetylchroman 
• 2039-47-6 2,2-dimethylchroman-6-carboxylic acid 
• 1198-96-5 2,2-dimethylchroman 
• 4294-57-9 para-methylphenylmagnesium bromide 
• 192762-69-9 ethyl 8-bromo-2,2-dimethylchroman-6-carboxylate 

Downstream Products

• 1442439-45-3 ethyl 4-[[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)-6-chromanyl]carbonyl]amino]benzoate 
• 1442439-46-4 4-[[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)-6-chromanyl]carbonyl]amino]benzoic acid 
• 192762-74-6 ethyl 2,6-difluoro-4-({[8-bromo-2,2-dimethyl-4-(4-methylphenyl)-6-chromanyl]carbonyl}amino)benzoate 
• 192762-73-5 ethyl 2-fluoro-4-[[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)-6-chromanyl]carbonyl]amino]benzoate 
• 192762-72-4 8-bromo-2,2-dimethyl-4-(4-methylphenyl)-4(2H)-chroman-6-carboxylic acid 

Relevant academic research and scientific papers

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

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 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 RARα for both compounds. Molecular modeling within the RARα binding pocket was used to compare binding interactions of the desfluoro analog to a known RAR antagonist.

Identification of highly potent retinoic acid receptor α-selective antagonists

The syntheses and full retinoid receptor characterization of a novel series of retinoic acid receptor α (RARα) antagonists, 1-5, are described. These compounds bind with high affinity to RARα but were completely inactive in gene transactivation. They were also potent and effective antagonists of retinoic acid (RA) induced gene transcription at RARα. Compounds 1-5 exhibited varying degrees of selectivity for RARα relative to RARβ/γ, with compound 5 being the most selective in both binding and functional antagonism assays. These compounds will be invaluable tools in delineating the physiological roles of RARα in development and in the adult animal and may themselves be useful therapeutic agents in human diseases associated with RARα.