Enzalutamide

Base Information

• Chemical Name: Enzalutamide
• CAS No.: 915087-33-1
• Molecular Formula: C21H16F4N4O2S
• Molecular Weight: 464.443
• Hs Code.: 29339900
• European Community (EC) Number: 805-022-1
• UNII: 93T0T9GKNU
• ChEMBL ID: CHEMBL1082407
• DSSTox Substance ID: DTXSID10912307
• Metabolomics Workbench ID: 65076
• NCI Thesaurus Code: C71744
• Nikkaji Number: J2.922.494C
• Pharos Ligand ID: A7M3QY3P22VZ
• RXCUI: 1307298
• Wikidata: Q1996756
• Wikipedia: Enzalutamide
• Mol file: 915087-33-1.mol

Synonyms:4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxo-1-imidazolidinyl)-2-fluoro-N-(methyl-d3)benzamide;4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxo-1-imidazolidinyl)-2-fluoro-N-methyl-benzamide;enzalutamide;enzalutamide D3;HC 1119;HC-1119;MDV 3100;MDV-3100;MDV3100;Xtandi

Chemical Property of Enzalutamide

Chemical Property:

• Refractive Index: 1.629
• PKA: 13.88±0.46(Predicted)
• PSA: 108.53000
• Density: 1.49g/cm³
• LogP: 4.51338
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO (>25 mg/ml)
• XLogP3: 3.6
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 3
• Exact Mass: 464.09300959
• Heavy Atom Count: 32
• Complexity: 839

Purity/Quality:

99% ^*data from raw suppliers

MDV 3100 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CC1(C(=O)N(C(=S)N1C2=CC(=C(C=C2)C(=O)NC)F)C3=CC(=C(C=C3)C#N)C(F)(F)F)C
• Recent ClinicalTrials: Enzalutamide and M9241 in PET Positive Recurrent Prostate Cancer (pprPC) Without Testosterone Lowering Therapy
• Recent EU Clinical Trials: A Multi-arm, Open-label Phase I/IIa Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of AZD5305 in Combination with New Hormonal Agents in Patients with Metastatic Prostate Cancer (PETRANHA)
• Recent NIPH Clinical Trials: Phase 2 platform study of combination therapy with pimitespib in patients with malignant tumors
• Indications: For the treatment of metastatic or recurrence of advanced male castration tolerance of prostate cancer.
• Description: In August 2012, the US FDA approved enzalutamide for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in patients who have previously been treated with docetaxel. Synthesis of enzalutamide was achieved by a triply convergent route that employed a Strecker condensation, followed by isothiocyanate condensation and hydrolysis to form the thiohydantoin moiety. In LNCaP/AR cells with high expression of AR, enzalutamide demonstrated potent inhibition of 16b-[18F]-5α-dihydrotestosterone binding (IC50=21 nM compared with bicalutamide IC50=160 nM), and inhibited AR translocation to the nucleus more potently than bicalutamide.The primary metabolite is the result of CYP2C8-mediated N-demethylation; enzalutamide is primarily eliminated by hepatic metabolism.
• Uses: MDV 3100 is an androgen-receptor antagonist that blocks androgens from binding to the androgen receptor and prevents nuclear translocation and co-activator recruitment of the ligand-receptor complex. MDV 3100 has also been shown to induce tumor cell apoptosis, and has no agonist activity. MDV 3100 is a candidate for the treatment of castration-resistant prostate cancer. MDV3100, known as Enzalutamide, is a second-generation androgen receptor (AR) signaling inhibitor. It is able to inhibit binding of androgens to the AR, AR nuclear translocation, and the association of the AR with DNA.
• Clinical Use: In August 2012, the FDA approved enzalutamide, marketed by Medivation and Astellas Pharma US for the treatment of metastatic castration-resistant prostate cancer (CRPC), specifically for those patients who had previously received docetaxel. Enzalutamide is an inhibitor of androgen receptors (AR)— whose increased expression has been closely linked with castration-resistant prostate cancer (CRPC),thus, AR inhibitors have seen increased recent attention from the medicinal chemistry community. Phase I/II trials were particularly promising for enzalutamide, as 43% of patients showed >50% sustained suppression of a key serum biomarker.
• Drug interactions: Potentially hazardous interactions with other drugs Anticoagulants: possibly reduces concentration effect of coumarinsAnxiolytics: concentration of midazolam reduced.Cytotoxics: concentration of palbociclib possibly reduced - avoid. Lipid-regulating drugs: concentration increased by gemfibrozil - avoid or halve enzalutamide dose.

Technology Process of Enzalutamide

There total 47 articles about Enzalutamide 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: 90.9%

2-(3-fluoro-4-(methylcarbamoyl)phenylamino)-2-methylpropionate allyl + 4-isothiocyanato 2-(trifluoromethyl)benzonitrile (143782-23-4) → enzalutamide (915087-33-1)

Guidance literature:

In dimethyl sulfoxide; at 80 ℃; for 4h; Concentration; Temperature;

Reference yield: 90.3%

2-methoxyethyl 2-{[3-fluoro-4-(methylcarbamoyl)phenyl]amino}-2-methylpropanoate + 4-isothiocyanato 2-(trifluoromethyl)benzonitrile (143782-23-4) → enzalutamide (915087-33-1)

Guidance literature:

In Isopropyl acetate; dimethyl sulfoxide; at 85 ℃; for 16h;

Reference yield: 88.7%

4-bromo-2-fluoro-N-methylbenzanamide (749927-69-3) + 2-(trifluoromethyl)-4-(4,4-dimethyl 5-oxo-2-thioimidazolin-1-yl)benzonitrile (143782-28-9) → enzalutamide (915087-33-1)

Guidance literature:

With copper(l) iodide; 2-acetylcyclohexanone; potassium carbonate; In N,N-dimethyl-formamide; at 110 ℃; for 22h; Inert atmosphere;

upstream raw materials:

N-methyl-2-fluoro-4-(1,1-dimethyl-cyanomethyl)-aminobenzamide

4-isothiocyanato 2-(trifluoromethyl)benzonitrile

thiophosgene

4-[1-(4-cyano-3-trifluoromethyl-phenylcarbamoyl)-1-methyl-ethylamino]-2-fluoro-N-methyl-benzamide

Downstream raw materials:

4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-2,4-dioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide

Refernces

• 1、 -. "Method for synthesizing enzalutamide (by machine translation)". . . Retrieved 2020/12/29.
• 2、 -. "Preparation process of medicine enzalutamide of prostate cancer (by machine translation)". . . Retrieved 2020/03/17.