Bicalutamide

Base Information

• Chemical Name: Bicalutamide
• CAS No.: 90357-06-5
• Molecular Formula: C18H14F4N2O4S
• Molecular Weight: 430.38
• Hs Code.: 29242995
• European Community (EC) Number: 618-534-3
• NSC Number: 759816,722665
• UNII: A0Z3NAU9DP
• DSSTox Substance ID: DTXSID2022678
• Nikkaji Number: J636.420I
• Wikipedia: Bicalutamide
• Wikidata: Q1988832
• NCI Thesaurus Code: C1599
• RXCUI: 83008
• Pharos Ligand ID: TS19J1PB4SYJ
• ChEMBL ID: CHEMBL409
• Mol file: 90357-06-5.mol

Synonyms:4'-cyano-3-(4-fluorophenylsulfonyl)-2-hydroxy-2-methyl-3'-(trifluoromethyl)propionanilide;bicalutamide;Casodex;Cosudex;ICI 176334;ICI-176334

Chemical Property of Bicalutamide

Chemical Property:

• Appearance/Colour: off-white crystalline solid
• Vapor Pressure: 8.47E-18mmHg at 25°C
• Melting Point: 191-193 °C
• Refractive Index: 1.577
• Boiling Point: 650.3 °C at 760 mmHg
• PKA: 11.49±0.29(Predicted)
• Flash Point: 347.1 °C
• PSA: 115.64000
• Density: 1.52 g/cm³
• LogP: 4.03338
• Storage Temp.: Store at RT
• Solubility.: DMSO: >5mg/mL
• XLogP3: 2.3
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 5
• Exact Mass: 430.06104075
• Heavy Atom Count: 29
• Complexity: 750

Purity/Quality:

99% ^*data from raw suppliers

Bicalutamide ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-24/25

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CC(CS(=O)(=O)C1=CC=C(C=C1)F)(C(=O)NC2=CC(=C(C=C2)C#N)C(F)(F)F)O
• Recent ClinicalTrials: Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial
• Recent EU Clinical Trials: Signal TrAnsduction Pathway activity analysis for OVarian cancER treatment. STAPOVER study
• Recent NIPH Clinical Trials: Investigation of neoadjuvant chemohormonal therapy before robot-assisted radical prostatectomy for the patients with high-risk prostate cancer.
• Description: Bicalutamide was launched in the United Kingdom, its first worldwide market, for the treatment of advanced prostate cancer in combination with an LHRH analog or surgical castration. A non-steroidal, peripherally selective antiandrogen, bicalutamide inhibits the action of dihydrotestosterone and testosterone at target sites by competitive binding to the cytosolic androgen receptor. It was reportedly well tolerated with no significant cardiovascular and metabolic side effects due to the benefit of lacking any steroid activity. The efficacy of bicalutamide as a monotherapy has been demonstrated clinically. Promising response rates were also reported in treating colorectal, breast, pancreas and non-small cell lung cancers.
• Uses: adrenocortical suppressant, antineoplastic, steroid biosynthesis inhibitor Non-steroidal peripherally active antiandrogen. Used as an antiandrogen, antineoplastic (hormonal) These Secondary Standards are qualified as Certified Reference Materials. These are suitable for use in several analytical applications including but not limited to pharma release testing, pharma method development for qualitative and quantitative analyses, food and beverage quality control testing, and other calibration requirements. Bicalutamide (CDX) has been used as an androgen receptor (AR) antagonist in prostate, bladder cancer cell lines and human fetal skeletal muscle cells. It has also been used as a supplement in RPMI 1640 for culturing androgen-independent LNCaP (LNCaP-AI) cell line.
• Indications: Bicalutamide was the third nonsteroidal anti-androgen that was used for the treatment of prostate cancer. Flutamide, although effective in the treatment of prostate cancer, is a pure antagonist that also affects the hypothalamus pituitary axis, thus preventing the negative feedback mechanism of androgen. Consequently, the production of LH is increased, which subsequently stimulates the synthesis of testosterone, counteracting the effectiveness of the anti-androgen. Furthermore, the half-life of the active metabolite of flutamide, hydroxyflutamide, is fairly short, and a dosing scheme of 250 mg three times daily is therefore required. The main adverse effects reported for flutamide are gynecomastia, diarrhea, and reversible liver abnormalities. Nilutamide has a longer half-life than flutamide and therefore can be administered once daily. Adverse events reported include problems with light/dark adaptation and interstitial pneumonitis. The goal that ultimately led to the discovery of bicalutamide was the identification of a novel peripherally selective anti-androgen with longer half-life than flutamide and with better tolerability as compared to both, flutamide and nilutamide.
• Clinical Use: Bicalutamide is a nonsteroidal pure antiandrogen given at a dosage of 150 mg once daily as monotherapy for the treatment of early (localized or locally advanced) nonmetastatic prostate cancer. It also can be used at a lower dosage in combination with a LHRH analogue or surgical castration for the treatment of advanced prostate cancer.
• Drug interactions: Potentially hazardous interactions with other drugs Anticoagulants: possibly enhances anticoagulant effect of coumarins. Lipid lowering agents: separate lomitapide and bicalutamide administration by 12 hours. See 'Other information'.

Technology Process of Bicalutamide

There total 45 articles about Bicalutamide 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: 100.0%

N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfanyl]-2-hydroxy-2-methylpropanamide (90356-78-8) → Bicalutamide (90357-06-5)

Guidance literature:

N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfanyl]-2-hydroxy-2-methylpropanamide; With potassium permanganate; tetra(n-butyl)ammonium hydrogensulfate; In water; ethyl acetate; at 25 - 30 ℃; for 2.5h;

With sodium metabisulfite; In water; ethyl acetate; for 1h;

Reference yield: 97.3%

4-Fluorothiophenol (371-42-6) + N-[4-cyano-3-(trifluoromethyl)phenyl]-2-methyloxirane-2-carboxamide (90357-51-0) → Bicalutamide (90357-06-5)

Guidance literature:

4-Fluorothiophenol; N-[4-cyano-3-(trifluoromethyl)phenyl]-2-methyloxirane-2-carboxamide; With sodium hydroxide; tetra(n-butyl)ammonium hydrogensulfate; In water; ethyl acetate; at 25 - 30 ℃; for 3h;

With potassium permanganate; In water; ethyl acetate; for 2.5h;

With sodium metabisulfite; In water; ethyl acetate; at 50 ℃; for 1h; Product distribution / selectivity;

Reference yield: 96.0%

N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfanyl]-2-hydroxy-2-methylpropanamide (90356-78-8) → N-[4-cyano-3-(trifluoromethyl)phenyl]-3-(4-fluorophenyl)sulfinyl-2-hydroxy-2-methyl-propanamide (945419-64-7,1080647-25-1) + Bicalutamide (90357-06-5)

Guidance literature:

With urea hydrogen peroxide adduct; In tetrahydrofuran; formic acid; water; at 27 - 35 ℃; for 1h;

upstream raw materials:

C₁₀H₁₁FO₅S

4-amino-2-trifluoromethylbenzonitrile

C₁₇H₁₉FO₂S

C₁₇H₁₉FO₄S

Downstream raw materials:

O-dibenzyl phosphoric acid ester of (R)-bicalutamide

phosphoric acid ester of (R)-bicalutamide

phosphoric acid ester of bicalutamide

O-dibenzyl phosphoric acid ester of bicalutamide

Refernces

Design, synthesis, and biological evaluation of 4-phenylpyrrole derivatives as novel androgen receptor antagonists

10.1016/j.bmc.2011.10.067

This research presents the design, synthesis, and biological evaluation of 4-phenylpyrrole derivatives as potential androgen receptor antagonists for the treatment of castration-resistant prostate cancer. The study aimed to develop novel orally available antagonists effective against both wild-type and mutant androgen receptors, including those resistant to existing therapies like bicalutamide. The researchers synthesized a series of 4-phenylpyrrole derivatives and evaluated their efficacy against prostate cancer cells, including those resistant to standard treatments. The compound 4n, in particular, showed strong inhibitory effects on tumor cell growth and was effective against both androgen-dependent and bicalutamide-resistant prostate cancer cells in mouse xenograft models. The chemicals used in the synthesis process included various 4-phenylpyrrole derivatives, reagents for organic synthesis such as nitroethane, nitromethane, benzaldehyde, and a range of catalysts and solvents necessary for the reactions, such as n-butylamine, potassium hydroxide, and tetrahydrofuran. The study concluded that the series of pyrrole compounds, with 4n as a lead, are novel androgen receptor antagonists with potential therapeutic effectiveness against prostate cancer, including castration-resistant forms.