Flutamide
[CAS# 13311-84-7]

Identification

• Classification: API >> Antineoplastic agents >> Hormone antineoplastic agents
• Name: Flutamide
• Synonyms: 2-Methyl-N-(4-nitro-3-[trifluoromethyl]phenyl)propanamide
• Molecular Formula: C₁₁H₁₁F₃N₂O₃
• Molecular Weight: 276.21
• CAS Registry Number: 13311-84-7
• EC Number: 236-341-9
• SMILES: CC(C)C(=O)NC1=CC(=C(C=C1)[N+](=O)[O-])C(F)(F)F

Properties

• Solubility: 100 mM (DMSO), 100 mM (ethanol) (Expl.)
• Density: 1.4±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.521, Calc.^*
• Boiling Point: 400.3±45.0 ºC (760 mmHg), Calc.^*
• Flash Point: 195.9±28.7 ºC, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07;GHS08 Danger
• Hazard Statements: H302+H312+H332-H302-H312-H332-H360-H361-H373-H413
• Precautionary Statements: P203-P260-P261-P264-P270-P271-P273-P280-P301+P317-P302+P352-P304+P340-P317-P318-P319-P321-P330-P362+P364-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Reproductive toxicity	Repr.	2	H361
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H312
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Chronic hazardous to the aquatic environment	Aquatic Chronic	4	H413
Reproductive toxicity	Repr.	1B	H360
Eye irritation	Eye Irrit.	2	H319
Carcinogenicity	Carc.	2	H351
Skin irritation	Skin Irrit.	2	H315
Reproductive toxicity	Repr.	1A	H360
Specific target organ toxicity - single exposure	STOT SE	1	H370
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Specific target organ toxicity - single exposure	STOT SE	3	H335
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412

Discovory and Applicatios

Flutamide is a synthetic nonsteroidal antiandrogen that was developed in the 1970s. It is primarily used in the treatment of prostate cancer, where it acts by inhibiting the effects of androgens, such as testosterone, on androgen-sensitive tissues. Flutamide works by binding to androgen receptors, thereby blocking the action of androgens, which are hormones responsible for the growth and proliferation of prostate cancer cells.

Flutamide is usually prescribed as part of a combination therapy for prostate cancer, particularly in patients who are undergoing androgen deprivation therapy. By preventing androgens from binding to their receptors, flutamide helps slow down or stop the growth of prostate cancer cells. It is commonly used in conjunction with other treatments such as surgical castration or luteinizing hormone-releasing hormone (LHRH) agonists to achieve maximal androgen blockade.

The drug was first introduced in the 1980s and has since become an important option for managing prostate cancer. In addition to its use in prostate cancer, flutamide has also been studied for its potential use in the treatment of other conditions influenced by androgens, such as hirsutism in women and as part of the management of androgenic alopecia.

Flutamide is taken orally, typically in the form of tablets, and is metabolized by the liver into its active form, which then exerts its antiandrogenic effects. Its use, however, is accompanied by potential side effects, the most notable of which include liver toxicity, gastrointestinal disturbances, and hot flashes. Liver function is closely monitored during treatment with flutamide due to the risk of hepatotoxicity.

Flutamide was once used in the treatment of other conditions such as polycystic ovary syndrome (PCOS) and excessive hair growth in women, but due to the availability of newer drugs and concerns over its side effects, its use for these purposes has become less common.

In the context of prostate cancer, flutamide continues to be a valuable option in certain treatment regimens. It plays a role in the androgen deprivation therapy, helping manage advanced prostate cancer and improving the quality of life for patients undergoing treatment. However, resistance to flutamide can develop over time, particularly in advanced cases, and newer drugs like enzalutamide and abiraterone have been introduced to address this challenge.

Overall, flutamide remains a significant therapeutic agent in the management of prostate cancer, and its discovery has contributed to the development of more targeted treatments for this disease. Its antiandrogenic properties continue to make it an important tool in the oncological field.

References

1991. Non-steroidal antiandrogens. Design of novel compounds based on an infrared study of the dominant conformation and hydrogen-bonding properties of a series of anilide antiandrogens. Journal of Medicinal Chemistry, 34(1).
DOI: 10.1021/jm00105a067

1991. Effect of combination endocrine therapy (LHRH agonist and flutamide) on normal prostate and prostatic adenocarcinoma. A histopathologic and immunohistochemical study. The American Journal of Surgical Pathology, 15(2).
DOI: 10.1097/00000478-199102000-00002

1987. Effect of flutamide on hepatic cytosolic methyltrienolone (R1881) binding kinetics and testosterone responsive hepatic drug and steroid metabolism in the adult male rat. Biochemical Pharmacology, 36(21).
DOI: 10.1016/0006-2952(87)90004-9