Bexarotene

Base Information

• Chemical Name: Bexarotene
• CAS No.: 153559-49-0
• Molecular Formula: C24H28O2
• Molecular Weight: 348.485
• Hs Code.: 29163990
• European Community (EC) Number: 681-650-8
• NSC Number: 747528
• UNII: A61RXM4375
• DSSTox Substance ID: DTXSID1040619
• Nikkaji Number: J612.549B
• Wikipedia: Bexarotene
• Wikidata: Q418192
• NCI Thesaurus Code: C1635
• RXCUI: 233272
• Pharos Ligand ID: 7HWH6ZBVJMRW
• Metabolomics Workbench ID: 42694
• ChEMBL ID: CHEMBL1023
• Mol file: 153559-49-0.mol

Synonyms:3-methyl-TTNEB;4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethenyl)benzoic acid;bexarotene;LG69 compound;LGD 1069;LGD-1069;LGD1069;Targretin

Chemical Property of Bexarotene

Chemical Property:

• Appearance/Colour: white solid
• Melting Point: 230-231 °C
• Boiling Point: 489.7 °C at 760 mmHg
• PKA: 4.08±0.10(Predicted)
• Flash Point: 229.5 °C
• PSA: 37.30000
• Density: 1.042 g/cm³
• LogP: 6.10370
• Storage Temp.: -20°C Freezer
• Solubility.: Soluble in DMSO and ethanol
• XLogP3: 7.6
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 3
• Exact Mass: 348.208930132
• Heavy Atom Count: 26
• Complexity: 551

Purity/Quality:

Bexarotene ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CC1=CC2=C(C=C1C(=C)C3=CC=C(C=C3)C(=O)O)C(CCC2(C)C)(C)C
• Recent ClinicalTrials: Bexarotene in Preventing Breast Cancer in Patients at High Risk for Breast Cancer
• Recent EU Clinical Trials: A randomised placebo-controlled study of the safety and tolerability of a retinoid-X receptor agonist's ability to promote remyelination in people with relapsing-remitting multiple sclerosis already on interferon-beta therapy: a phase 2a trial
• Recent NIPH Clinical Trials: Continuous administration trial of phase II study of BSC-1 in patients with ATL
• Description: Bexarotene was launched in the US for the treatment of manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy. The four step synthesis of bexarotene involves a double Friedel-Craft alkylation of toluene with 2,5-dichloro-2,5-dimethylhexane followed by acylation with monomethylterephthalic acid chloride, then Wittig methylidenation. Bexarotene is the first retinoid X receptor (RXR) agonist to be selective versus retinoid A receptors (RAR). Its activation of the three RXRα, β, γ isoforms induces cell differentiation and apoptosis and inhibits cell proliferation in several models of cancer. In phase ll/lll clinical trials, 48% of patients with refractory or persistent early-stage cutaneous T-cell lymphoma achieved a complete or partial response when treated with 300 mg/m2/day of bexarotene. It was shown in phase I trials that this second-generation retinoid was substantially less toxic than the broad-spectrum or RARselective retinoids. Bexarotene is an agonist of retinoid X receptors (RXRs; EC50s = 28, 25, and 20 nM for RXRα, RXRβ, and RXRγ, respectively, in reporter assays). It is selective for RXRs over retinoic acid receptors (RARs; EC50s = >10 μM for RARα, RARβ, and RARγ). Bexarotene (10 μM) induces apoptosis in MJ, HuT 78, and HH cutaneous T cell lymphoma (CTCL) cells, as well as inhibits lung metastasis and angiogenesis in A549 and MDA-MB-231 mouse xenograft models when administered at a dose of 100 mg/kg per day. It reduces increased brain interstitial fluid levels of amyloid-β (1-40) (Aβ40) and Aβ42 in the APP/PS1 transgenic mouse model of Alzheimer’s disease. It also reduces viral load in the culture supernatant of Vero E6 cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; EC90 = 9.4 μM) and inhibits SARS-CoV-2 replication in a plaque reduction assay (EC50 = 2.01 μM). Formulations containing bexarotene have been used in the treatment of CTCL.
• Uses: Used as an antineoplastic. A selective retinoid X receptor (RXR) agonist Bexarotene is used as a Synthetic retinoid analog with specific affinity for the retinoid X receptor, an antineoplastic agent, already approved as an oral antineoplastic agent for cutaneous T cell lymphoma and being investigated against other cancers. A study has found that bexarotene in a mouse Alzheimer?s model lowered the most toxic form of β-amyloid peptide and increased cognitive ability.
• Indications: Bexarotene (Targretin) belongs to a subclass of retinoids that selectively bind to and activates retinoid X receptors (RXRs), which have biological properties distinct from those of RARs. In vitro, bexarotene exerts antiproliferative effects on some tumor lines of hematopoietic and squamous cell origin.
• Therapeutic Function: Antineoplastic
• Clinical Use: Antineoplastic agent: Treatment of skin manifestations of cutaneous T-cell lymphoma
• Drug interactions: Potentially hazardous interactions with other drugs Antipsychotics: avoid with clozapine (increased risk of agranulocytosis) Lipid-regulating drugs: concentration increased by gemfibrozil - avoid.

Technology Process of Bexarotene

There total 31 articles about Bexarotene which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 93.0%

methyl 4-<1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)ethenyl>benzoate (153559-48-9) → bexarotene (153559-49-0)

Guidance literature:

With potassium hydroxide; In methanol; Heating;

Reference yield: 89.0%

ethyl 4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzoate (1346970-00-0) → bexarotene (153559-49-0)

Guidance literature:

With potassium hydroxide; In methanol; for 2h; Inert atmosphere; Reflux;

DOI:10.1002/chem.201203646

Reference yield: 66.0%

carbon dioxide (124-38-9,18923-20-1) + C24H27F3O3S → bexarotene (153559-49-0)

Guidance literature:

With (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate; palladium diacetate; caesium carbonate; N-ethyl-N,N-diisopropylamine; DavePhos; In N,N-dimethyl acetamide; at 20 ℃; for 36h; chemoselective reaction; Irradiation; Green chemistry;

DOI:10.1021/acs.orglett.9b01532

upstream raw materials:

methyl 4-<1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)ethenyl>benzoate

2,5-dimethyl-2,5-hexanediol

2,5-dichloro-2,5-dimethyl hexane

methyl 4-acetylbenzoate

Downstream raw materials:

4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzaldehyde O-methyl oxime

4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzaldehyde oxime

4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzaldehyde

(4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)phenyl)methanol

Refernces

• 1、 Bhunia, Samir Kumar,Das, Pritha,Nandi, Shantanu,Jana, Ranjan. "Carboxylation of Aryl Triflates with CO2 Merging Palladium and Visible-Light-Photoredox Catalysts". . p. 4632 - 4637. Retrieved 2019/06/27.
• 2、 Yoshida,Shinke,Kawano,Takaki. "Copper-catalyzed α-selective hydrostannylation of alkynes for the synthesis of branched alkenylstannanes". supporting information. p. 10616 - 10619. Retrieved 2015/06/30.