Flutamide

Base Information

• Chemical Name: Flutamide
• CAS No.: 13311-84-7
• Deprecated CAS: 37209-54-4
• Molecular Formula: C11H11F3N2O3
• Molecular Weight: 276.215
• Hs Code.: 29242990
• European Community (EC) Number: 236-341-9
• NSC Number: 757817,147834,215876
• UNII: 76W6J0943E
• DSSTox Substance ID: DTXSID7032004
• Nikkaji Number: J8.099C
• Wikipedia: Flutamide
• Wikidata: Q418669
• NCI Thesaurus Code: C509
• RXCUI: 4508
• Pharos Ligand ID: WXMVB3PNUN1B
• Metabolomics Workbench ID: 42843
• ChEMBL ID: CHEMBL806,CHEMBL4759307
• Mol file: 13311-84-7.mol

Synonyms:Apimid;Apo Flutamide;Apo-Flutamide;ApoFlutamide;Chimax;Cytamid;Drogenil;Euflex;Eulexin;Eulexine;Fluken;Flulem;Flumid;Fluta 1A Pharma;Fluta cell;Fluta GRY;Fluta-cell;Fluta-GRY;Flutacell;FlutaGRY;Flutamide;Flutamin;Flutandrona;Flutaplex;Flutexin;Fugerel;Grisetin;Niftolid;Niftolide;Novo Flutamide;Novo-Flutamide;NovoFlutamide;Oncosal;PMS Flutamide;PMS-Flutamide;Prostacur;Prostica;Prostogenat;SCH 13521;SCH-13521;SCH13521;Testotard

Chemical Property of Flutamide

Chemical Property:

• Appearance/Colour: light yellow solid
• Melting Point: 112 °C
• Refractive Index: 1.477
• Boiling Point: 400.3 °C at 760 mmHg
• PKA: 13.12±0.70(Predicted)
• Flash Point: 195.9 °C
• PSA: 74.92000
• Density: 1.372 g/cm³
• LogP: 3.80430
• Storage Temp.: Store at RT
• Solubility.: Practically insoluble in water, freely soluble in acetone and in ethanol (96 per cent).
• XLogP3: 3.3
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 2
• Exact Mass: 276.07217670
• Heavy Atom Count: 19
• Complexity: 352

Purity/Quality:

99% ^*data from raw suppliers

Flutamide ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn,Xi
• Hazard Codes: Xn,Xi
• Statements: 20/21/22-63-36/37/38
• Safety Statements: 22-36-36/37/39-27-26

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CC(C)C(=O)NC1=CC(=C(C=C1)[N+](=O)[O-])C(F)(F)F
• Recent ClinicalTrials: Three Drug Combination Therapy Versus Conventional Treatment of Children With Congenital Adrenal Hyperplasia
• Recent EU Clinical Trials: Randomised phase 3 trial of enzalutamide in androgen deprivation therapy with radiation therapy for high risk, clinically localised, prostate cancer.
• Recent NIPH Clinical Trials: 1st Ra-223 Therapy Trial
• Description: Flutamide is a kind of synthetic, non-steroidal antiandrogen which is mainly used for the treatment of prostate cancer. It is a kind of toluidine derivative and a nonsteroidal antiandrogen with a similar structure of bicalutamide and nilutamide. The mechanism of its anti-cancer property is through acting as a selective antagonist of the androgen receptor (AR), preventing androgens such as testosterone and its active metabolite dihydrotestosterone from binding to ARs in the prostate gland. This process inhibits androgen-dependent DNA and protein synthesis in the tumor cell. Therefore, it can prevent androgens from stimulating the growth of prostate cancer cells. Moreover, it can also be used for the treatment of hyperandrogenism in women. It is quite effective in alleviating symptoms such as acne, seborrhea, hirsutism and androgenetic alopecia. Finally, it is also useful as a component in the transgender hormone therapy. Flutamide is an orally active, non-steroidal antiandrogen indicated for the treatment of prostatic cancer in both castrates and noncastrates.
• Uses: Antiandrogen; antineoplastic (hormonal). neuroleptic Flutamide is a nonsteroidal antiandrogen drug; antineoplastic (hormonal). Besides prostate cancer, flutamide has also been tested and/or used off-label in other hyperandrogenism-related disorders like benign prostatic hyperplasia, acne vulgaris, and hirsutism syndrome. Due to its teratogenic potential, flutamide is restricted for premenopausal women and used only in combination with effective contraception.
• Indications: Flutamide is a prodrug possessing only weak androgen antagonistic activity of its own. It is oxidized in vivo to the active principle hydroxyflutamide (6) as primary metabolite.The elimination half-life of hydroxyflutamide is relatively short, 4–6.6 h in patients after a single oral 250 mg dose of flutamide. Therefore, oral dosing of 250 mg flutamide three times daily was applied clinically. The first introduction into clinical studies was achieved in 1975 as single agent in the first-line treatment of advanced prostate carcinoma. In the United States, flutamide was finally approved by FDA in 1989 for the treatment of metastatic prostate cancer in combination with a luteinizing hormone-releasing hormone (LHRH, also referred to as gonadotropin-releasing hormone (GnRH)) agonist, for instance, leuprorelin acetate (Leuprolide(R), Lupron(R)) or goserelin acetate (Zoladex(R)).The combined androgen blockade by flutamide plus an LHRH agonist or surgical castration was introduced in order to maximize the effects of androgen ablation. Flutamide also inhibits the secretion of androgens from the adrenal gland, which is not impaired by chemical castration with LHRH agonists or by surgical castration. In addition, the AR antagonist avoids the unacceptable initial tumor flare that occurs when LHRH agonists are given alone. Favorable response to flutamide was seen with advanced prostate carcinoma patients after single-agent treatment as well as after combination treatment. The progression of the disease was slowed and the lifetime of patients was extended. For instance, the National Cancer Institute (NCI) initiated a trial (INT-0036) and concluded that the combination of leuprolide with flutamide was more effective than leuprolide alone in patients with advanced prostate cancer. However, significant side effects were also reported.The most frequently observed adverse events are summarized in Table 1. Flutamide evidently amplifies some of the LHRH agonist-induced side effects. Table 1 Side effects of LHRH antagonist alone and in combination with flutamide. Flutamide (Eulexin) is a nonsteroidal androgen receptor antagonist that inhibits androgen binding to its nuclear receptor. It is effective in inducing prostatic regression and is approved for the treatment of prostatic carcinoma. For maximum clinical effectiveness it has to be used in combination with a GnRH antagonist (e.g., leuprolide acetate) that inhibits androgen production. Flutamide may eventually be used for the treatment of hirsutism and male pattern baldness in women if a topical preparation is developed. Flutamide (Eulexin) is a nonsteroidal antiandrogen compound that competes with testosterone for binding to androgen receptors. The drug is well absorbed on oral administration. It is an active agent in the hormonal therapy of cancer of the prostate and has been shown to complement the pharmacological castration produced by the gonadotropin-releasing hormone (GnRH) agonist leuprolide. Flutamide prevents the stimulation of tumor growth that may occur as a result of the transient increase in testosterone secretion after the initiation of leuprolide therapy. The most common side effects of flutamide are those expected with androgen blockade: hot flashes, loss of libido, and impotence. Mild nausea and diarrhea occur in about 10% of patients.
• Therapeutic Function: Antiandrogen
• Clinical Use: Flutamide is a pure antagonist, whereas 2-hydroxyflutamide is a more potent AR antagonist but also can activate the androgenic receptor at higher concentrations. These findings raise the possibility that increased conversion of flutamide to 2-hydroxyflutamide or accumulation of 2-hydroxyflutamide in cells may contribute to the anomalous responses to flutamide that are observed in some advanced prostate cancers.
• Drug interactions: Potentially hazardous interactions with other drugs Anticoagulants: effects of coumarins enhanced

Technology Process of Flutamide

There total 11 articles about Flutamide 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: 99.0%

N-(3-iodo-4-nitrophenyl)isobutyramide (1456616-25-3) + trimethylsilyl 2-chloro-2,2-difluoroacetate → Flutamide (13311-84-7)

Guidance literature:

With copper(l) iodide; N,N,N,N,-tetramethylethylenediamine; silver fluoride; In N,N-dimethyl-formamide; at 100 ℃; Sealed tube; Inert atmosphere;

DOI:10.1021/acs.oprd.6b00079

Reference yield: 86.0%

4-bromo-1-nitro-2-(trifluoromethyl)benzene (344-38-7) + potassium (2-methyl-1-((trimethylsilyl)oxy)propylidene)amide → Flutamide (13311-84-7)

Guidance literature:

potassium (2-methyl-1-((trimethylsilyl)oxy)propylidene)amide; With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; XPhos; In 1,4-dioxane; at 100 ℃; for 0.166667h;

4-bromo-1-nitro-2-(trifluoromethyl)benzene; In 1,4-dioxane; at 100 ℃; for 16h;

DOI:10.1055/s-0035-1560724

Reference yield: 83.3%

2-methyl-N-[3-(trifluoromethyl)phenyl]propionamide (1939-27-1) → Flutamide (13311-84-7)

Guidance literature:

With sulfuric acid; nitric acid; at -5 ℃; for 3h;

upstream raw materials:

4-nitro-3-(trifluoromethyl)benzeneamine

isobutyryl chloride

2-methyl-N-[3-(trifluoromethyl)phenyl]propionamide

3-trifluoromethylaniline

Downstream raw materials:

4-nitro-3-(trifluoromethyl)benzeneamine

N-[4-amino-3-(trifluoromethyl)phenyl]acetamide

2-methyl-N-[4-amino-3-(trifluoromethyl)phenyl]propanamide

dihydrogen peroxide

Refernces

• 1、 Pedersen, Simon S.,Donslund, Aske S.,Mikkelsen, Jesper H.,Bakholm, Oskar S.,Papp, Florian,Jensen, Kim B.,Gustafsson, Magnus B. F.,Skrydstrup, Troels. "A Nickel(II)-Mediated Thiocarbonylation Strategy for Carbon Isotope Labeling of Aliphatic Carboxamides". . p. 7114 - 7123. Retrieved 2021.
• 2、 -. "Synthesis method of drug intermediate flutamide". Paragraph 0008; 0010-0028. . Retrieved 2018/06/21.