153559-98-9

Upstream product

• 153559-49-0 bexarotene 

Downstream Products

• 1380681-81-1 DW₂₂ 
• 926038-66-6 6-(1-(4-iodophenyl)vinyl)-1,1,4,4,7-pentamethyl-1,2,3,4-tetrahydronaphthalene 
• 1356550-80-5 N-(2-aminoethyl)-4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzamide 

Relevant academic research and scientific papers

A one-pot synthesis of tetrazolones from acid chlorides: Understanding functional group compatibility, and application to the late-stage functionalization of marketed drugs

A one-pot and scalable synthesis of tetrazolones (tetrazol-5-ones) from acid chlorides using azidotrimethylsilane is presented. The reaction tolerates many functional groups and can furnish aryl-, heteroaryl-, alkenyl-, or alkyl-substituted tetrazolone products in moderate to excellent yield (14-94%). No reduction in yield was observed when the reaction was undertaken on a larger-scale (20-36 g). The method could be used for the late-stage functionalization of pharmaceuticals, to provide tetrazolone congeners of the marketed drugs aspirin, indomethacin, probenecid, telmisartan, bexarotene, niacin (vitamin B3), and the active metabolite of the recently-launched immuno-modulatory agent, BG-12 (Tecfidera). The ability of a tetrazolone group to serve as a bioisostere of a carboxylic acid, and to improve drug pharmacokinetic profiles is also highlighted.

Discovering alkylamide derivatives of bexarotene as new therapeutic agents against triple-negative breast cancer

Triple-negative breast cancer (TNBC) has been reported to be correlated with high expression of proliferation markers as well as constitutive activation of metastasis-relevant signaling pathways. For many years, breast cancer researchers have been investi

New highly cytotoxic organic and organometallic bexarotene derivatives

A series of bifunctional ruthenium(II) arene compounds modified with bexarotene, a retinoid that selectively activates retinoid X receptors inducing cell differentiation and apoptosis and preventing drug resistance, are described. The bexarotene is tethered to the ruthenium(II) arene fragment via an imidazole linker. Both the bexarotene-imidazole ligand and ruthenium(II) arene complexes are considerably more cytotoxic than the parent drug bexarotene. Docking studies show that the interactions of these compounds with possible targets are significantly different to the binding mode of the parent drug.

Tetrazolone as an acid bioisostere: Application to marketed drugs containing a carboxylic acid

Matched molecular pair analysis was used to evaluate the ability of a tetrazolone group to act as a bioisostere of a carboxylic acid. Compound 7, a tetrazolone of the anti-hypertensive drug, telmisartan 6, was shown to be a potent AT1 antagonist (Kb = 0.14 nM), with activity comparable to telmisartan itself (Kb = 0.44 nM). Additionally, compound 9, a tetrazolone congener of the marketed anti-cancer agent, bexarotene 8, was shown to be an agonist at the retinoid X receptor alpha (EC50 = 64 nM). Compounds containing a tetrazolone group showed similar microsomal stability and plasma protein binding to marketed acid counterparts, while also reducing the value for clog P. Furthermore, compound 7 displayed an improved rat pharmacokinetic profile cf. telmisartan 6. Taken together, the results demonstrate that a tetrazolone group may serve as a bioisostere for a carboxylic acid.

Decarbonylative Suzuki-Miyaura Cross-Coupling of Aroyl Chlorides

Herein, we report a catalyst system for Pd-catalyzed decarbonylative Suzuki-Miyaura cross-coupling of aroyl chlorides with boronic acids to furnish biaryls. This strategy is suitable for a broad range of common aroyl chlorides and boronic acids. The synthetic utility is highlighted in the direct late-stage functionalization of pharmaceuticals and natural products capitalizing on the presence of carboxylic acid moiety. Extensive mechanistic and DFT studies provide key insight into the reaction mechanism and high decarbonylative cross-coupling selectivity.

Antiproliferative activity of Pt(IV) complexes with lonidamine and bexarotene ligands attached via succinate-ethylenediamine linker

We present the synthesis and cytotoxic potencies of new Pt(IV) complexes with lonidamine and bexarotene ligand tethered to Pt-center via a succinate-ethylenediamine linker. The in vitro results for a series of complexes with cisplatin, dichloride(ethane-1,2-diamine)platinum(II), or oxaliplatin core indicate that the addition to the structure lonidamine or bexarotene moiety can confer activity or selectivity of Pt(IV) complexes.

Palladium-Catalyzed Decarbonylative Difluoromethylation of Acid Chlorides at Room Temperature

Methods for the direct synthesis of difluoromethylated arenes are sparse, despite the importance of the difluoromethyl group in medical, agro-, and materials chemistry. A palladium-catalyzed decarbonylative cross-coupling reaction of acid chlorides with a difluoromethyl zinc reagent is achieved to access difluoromethylated compounds. The transformation proceeds at room temperature and shows broad functional group tolerance, thus providing a general and efficient method for decarbonylative difluoromethylation of a wide range of aromatic carboxylic acids.

Tetrazolones as a Carboxylic Acid Bioisosteres

The present disclosure provides compounds that include a tetrazolone derivative of a carboxyl group of an active agent. This disclosure also relates to pharmaceutical compositions that include these compounds, methods of using these compounds in the treatment of various diseases and disorders, and processes for preparing these compounds.

Discovery of a small molecular compound simultaneously targeting RXR and HADC: Design, synthesis, molecular docking and bioassay

Retinoid X receptor (RXR) and Histone deacetylase (HDAC) are considered important targets for anti-cancer therapy due to their crucial roles in genetic or epigenetic regulations of cancer development and progression. Here, we have designed and synthesized a novel compound which targets both RXR and HADC. This dual-targeting agent is derived from bexarotene and suberoylanilide hydroxamic acid (SAHA), prototypical RXR agonist and HDAC inhibitor, respectively. Molecular docking studies demonstrate that this agent has a relatively strong affinity to RXR and HADC. Importantly, it presents the potentials of activation of RXR and inhibition of HDAC in both cell-free and whole-cell assays, and displays anti-proliferative effect on representative cancer cell lines and drug-resistant cancer cell lines.