188889-06-7

Basic information

• Product Name: 6-BroMo-1,1-diMethyl-4-p-tolyl-1,2-dihydro-naphthalene
• Synonyms: 6-BroMo-1,1-diMethyl-4-p-tolyl-1,2-dihydro-naphthalene
• CAS NO: 188889-06-7
• Molecular Formula: C₁₉H₁₉Br
• Molecular Weight: 327.25816
• Mol File: 188889-06-7.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 6-BroMo-1,1-diMethyl-4-p-tolyl-1,2-dihydro-naphthalene(CAS DataBase Reference)
• NIST Chemistry Reference: 6-BroMo-1,1-diMethyl-4-p-tolyl-1,2-dihydro-naphthalene(188889-06-7)
• EPA Substance Registry System: 6-BroMo-1,1-diMethyl-4-p-tolyl-1,2-dihydro-naphthalene(188889-06-7)

Safety Data

• Hazardous Substances Data: 188889-06-7(Hazardous Substances Data)

Upstream product

• 188889-04-5 7-bromo-4,4-dimethyl-1-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-ol 
• 4294-57-9 para-methylphenylmagnesium bromide 
• 166978-46-7 7-bromo-4,4-dimethyl-3,4-dihydro-2H-naphthalen-1-one 
• 60-29-7 diethyl ether 

Downstream Products

• 166978-45-6 5,6-dihydro-5,5-dimethyl-8-(4-methylphenyl)-2-naphthalenecarboxylic acid 
• 192762-68-8 ethyl 2,6-difluoro-4-({[5,6-dihydro-5,5-dimethyl-8-(4-methylphenyl)-2-naphthalenyl]carbonyl}amino)benzoate 
• 188888-45-1 ethyl 2-fluoro-4-[[(5,6-dihydro-5,5-dimethyl-8-(4-methylphenyl)-2-naphthalenyl)carbonyl]amino]-benzoate 
• 188888-33-7 ethyl 4-(5,5-dimethyl-8-(p-tolyl)-5,6-dihydronaphthalene-2-carboxamido)benzoate 
• 204449-10-5 4-{1-[1-(5,5-Dimethyl-8-p-tolyl-5,6-dihydro-naphthalen-2-yl)-meth-(E)-ylidene]-3,3-dimethoxy-propyl}-benzoic acid ethyl ester 
• 204449-13-8 4-{1-[1-[5,5-Dimethyl-8-(5-methyl-thiophen-2-yl)-5,6-dihydro-naphthalen-2-yl]-meth-(E)-ylidene]-3,3-dimethoxy-propyl}-benzoic acid ethyl ester 
• 204449-09-2 5,5-dimethyl-8-p-tolyl-5,6-dihydro-naphthalene-2-carbaldehyde 

Relevant articles and documents

Pharmacological activity of retinoic acid receptor alpha-selective antagonists in vitro and in vivo

Oral administration of a retinoic acid receptor (RAR) pan-antagonist reversibly inhibits spermatogenesis. Given the importance of RARα in regulating spermatogenesis, we identified two RARα-selective antagonists by transactivation and transactivation competition assays and asked whether they effectively inhibit spermatogenesis. Although these two antagonists were potent in vitro, they displayed poor in vivo activity in mice when administered orally. Testicular weights were normal, and morphological analysis revealed normal spermatid alignment and sperm release. In vitro drug property analyses were performed with one of these antagonists and compared with the pan-antagonist. We showed that the discrepancies may be explained by several factors, including high plasma protein binding, faster hepatic metabolism relative to the pan-antagonist, and only moderate permeability. The conclusion of poor oral bioavailability was supported by more pronounced defects in mice when the antagonist was administered intravenously versus intraperitoneally. These results are crucial for designing new RARα-selective antagonists for pharmaceutical application.

Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities

Aryl-substituted and aryl and (3-oxo-1-propenly)-substituted benzopyran, benzothiopyran, 1,2-dihydroquinoline, and 5,6-dihydronaphthalene derivatives have retinoid negative hormone and/or antagonist-like biological activities. The invented RAR antagonists can be administered to mammals, including humans, for the purpose of preventing or diminishing action of RAR agonists on the bound receptor sites. Specifically, the RAR agonists are administered or coadministered with retinoid drugs to prevent or ameliorate toxicity or side effects caused by retinoids or vitamin A or vitamin A precursors. The retinoid negative hormones can be used to potentiate the activities of other retinoids and nuclear receptor agonists. For example, the retinoid negative hormone called AGN 193109 effectively increased the effectiveness of other retinoids and steroid hormones in in vitro transactivation assays. Additionally, transactivation assays can be used to identify compounds having negative hormone activity. These assays are based on the ability of negative hormones to down-regulate the activity of chimeric retinoid receptors engineered to possess a constitutive transcription activator domain.

SYNTHESIS AND USE OF RETINOID COMPOUNDS HAVING NEGATIVE HORMONE AND/OR ANTAGONIST ACTIVITIES

2,2-Dialkyl-4-aryl-substituted benzopyran and benzothiopyran derivatives of the formula STR1 where the symbols have the meaning described in the specification, have retinoid negative hormone and/or antagonist-like biological activities. The invented RAR antagonists can be administered to mammals, including humans, for the purpose of preventing or diminishing action of RAR agonists on the bound receptor sites. Specifically, the RAR agonists are administered or coadministered with retinoid drugs to prevent or ameliorate toxicity or side effects caused by retinoids or vitamin A or vitamin A precursors. The retinoid negative hormones can be used to potentiate the activities of other retinoids and nuclear receptor agonists.

A new class of potent RAR antagonists: Dihydroanthracenyl, benzochromenyl and benzothiochromenyl retinoids

The synthesis and biological activity of a novel series of tricyclic retinoic acid receptor antagonists are described. These compounds bind with high affinity to the RARs and are potent antagonists of retinoid function in in vitro and in vivo systems.

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.