Flutamide 13311-84-7 wiki

1. Names and Identifiers

1.1 Name: Flutamide
1.2 Synonyms: [14C]-Flutamide 2-METHYL-N-(4'-NITRO-3'-(TRIFLUOROMETHYL)PHENYL)PROPANAMIDE 2-METHYL-N-(4-NITRO-3-[TRIFLUOROMETHYL]PHENYL)PROPANAMIDE 2-Methyl-N-(4-nitro-3-[trifluoromethyl]phenyl)propanamide,Flutamide 2-Methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide 2-Methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propionamide 2-Methyl-N-[4-nitro-3-(trifluoromethyl)-phenyl]-propionamide 4'-Nitro-3'-(trifluoromethyl)isobutyranilide 4'-nitro-3'-trifluoromethylisobutyranilide AURORA KA-860 Drogenil EINECS 236-341-9 Eulexin Flutamida Flutamide USP25 Flutamidum Flutamin FXFFR BNW EMVY1&1 MFCD00072009 N1-[4-NITRO-3-(TRIFLUOROMETHYL)PHENYL]-2-METHYLPROPANAMIDE NFBA Niftholide niftolid Niftolide Propanamide, 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]- TIMTEC-BB SBB006930

1.3 CAS No.: 13311-84-7

1.4 CID: 3397

1.5 EINECS(EC#): 236-341-9

1.6 Molecular Formula: C11H11F3N2O3 (isomer)

1.7 Inchi: InChI=1S/C11H11F3N2O3/c1-6(2)10(17)15-7-3-4-9(16(18)19)8(5-7)11(12,13)14/h3-6H,1-2H3,(H,15,17)

1.8 InChkey: MKXKFYHWDHIYRV-UHFFFAOYSA-N

1.9 Canonical Smiles: CC(C)C(=O)NC1=CC(=C(C=C1)[N+](=O)[O-])C(F)(F)F

1.10 Isomers Smiles: CC(C)C(=O)NC1=CC(=C(C=C1)[N+](=O)[O-])C(F)(F)F

2. Properties

2.1 Density: 1.372

2.1 Melting point: 112 °C

2.1 Boiling point: 400.3 °C at 760 mmHg

2.1 Refractive index: 1.477

2.1 Flash Point: 195.9 °C

2.1 Precise Quality: 276.07200

2.1 PSA: 74.92000

2.1 logP: 3.80430

2.1 Appearance: Light Yellow Solid

2.2 Storage: Store at RT

2.3 Chemical Properties: Light Yellow Solid

2.4 Contact Allergens: Flutamide is an antiandrogenic hormonal antineoplas tic drug that can induce photosensitivity and porphy ria-like eruption.

2.5 pKa: 13.12±0.70(Predicted)

2.6 Water Solubility: SOLUBILITY IN WATER Insoluble

2.7 Stability: Stable at normal temperatures and pressures.

2.8 StorageTemp: 2-8°C

3. Use and Manufacturing

3.1 General Description: Flutamide, 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide, is dosed 3 times daily(250-mg dose; 750-mg total daily dose). A major metaboliteof flutamide, hydroxyflutamide, is a more potent AR antagonistthan the parent compound. This metabolite, which ispresent at a much higher steady-state concentration than isflutamide, contributes a significant amount of the antiandrogen action of this drug. A limiting factor in the useof flutamide is hepatotoxicity in from 1% to 5% of patients.Although the hepatotoxicity usually is reversible followingcessation of treatment, rare cases of death associated withhepatic failure have been reported to be associated with flutamidetherapy. Diarrhea is also a limiting side effect withflutamide therapy for some patients.

3.2 History: Flutamide was first described as a member of a series of N-acyl anilides synthesized at Monsanto in the 1960s during a compound finding program aiming at bacteriostatic agents. Soon after, at Schering Corp., the compound was characterized pharmacologically and further developed as SCH-13521. It was found that flutamide inhibits agonist action at the AR by replacing the agonist at the ligand binding site, being the first nonsteroidal compound possessing anti-androgenic activity in animals. In contrast to steroidal anti-androgens, for instance, cyproterone acetate, which also displays significant progestational activity, flutamide has no other hormonal activity. There is also no reduction of serum testosterone levels seen with flutamide but rather a slight increase in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) resulting in elevated serum testosterone levels. This accounts for the beneficial maintenance of libido and potency in sexually active patients. On the other hand, elevated serum estradiol levels resulting from peripheral testosterone aromatization leading to gynecomastia were observed in patients.

3.3 Usage: Antiandrogen; antineoplastic (hormonal).

4. Safety and Handling

4.1 Symbol: GHS07, GHS08

4.1 Hazard Codes: Xn

4.1 Signal Word: Warning

4.1 Risk Statements: R20/21/22;R63

4.1 Safety Statements: S22;S36

4.1 Hazard Declaration: H302 + H312 + H332-H361

4.1 RIDADR: NONH for all modes of transport

4.1 Caution Statement: P261-P280-P301 + P312 + P330

4.1 WGK Germany: 3

4.1 RTECS: UG5700000

4.1 Report

The Flutamide, with the cas registry number 13311-84-7, has the IUPAC name of 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide. Being a kind of light yellow solid, it is nearly insoluble in water, and it is usually used as the Antiandrogen and antineoplastic (hormonal). Besides, its product categories are including Aromatic Carboxylic Acids, Amides, Anilides, Anhydrides & Salts; APIs; Antitumors for Research and Experimental Use; Biochemistry; Amines; Aromatics; Intermediates & Fine Chemicals; Pharmaceuticals; API's.

The characteristics of this chemical are as follows: (1)ACD/LogP: 3.72; (2)# of Rule of 5 Violations: 0; (3)ACD/LogD (pH 5.5): 3.72; (4)ACD/LogD (pH 7.4): 3.72; (5)ACD/BCF (pH 5.5): 392.97; (6)ACD/BCF (pH 7.4): 392.97; (7)ACD/KOC (pH 5.5): 2504.06; (8)ACD/KOC (pH 7.4): 2504.05; (9)#H bond acceptors: 5; (10)#H bond donors: 1; (11)#Freely Rotating Bonds: 3; (12)Polar Surface Area: 66.13; (13)Index of Refraction: 1.52; (14)Molar Refractivity: 61.27 cm³; (15)Molar Volume: 201.2 cm³; (16)Polarizability: 24.29 ×10^-24 cm³; (17)Surface Tension: 38.2 dyne/cm; (18)Density: 1.372 g/cm³; (19)Flash Point: 195.9 °C; (20)Enthalpy of Vaporization: 65.11 kJ/mol; (21)Boiling Point: 400.3 °C at 760 mmHg; (22)Vapour Pressure: 1.29E-06 mmHg at 25°C; (23)Exact Mass: 276.072177; (24)MonoIsotopic Mass: 276.072177; (25)Topological Polar Surface Area: 74.9; (26)Heavy Atom Count: 19; (27)Formal Charge: 0; (28)Complexity: 352.

The production method of this chemical is as below: After the nitrification of benzenyl trifluoride to have m-nitrotrifluorinemethylbenzene, and then restore to have m-trifluorinemethylaniline; Next react with iso-butyryl chloride and then go through the nitrification to produce Flutamide.?

As to its usage, it is widely applied in many ways. It could be used as the NAISD male sex hormone antagonist which could restrain teststrone transforming into dihydro-testosterone; It could also be used in curing the diseases of PCa(prostatic cancer) and prostatic hyperplasia.

When you are dealing with this chemical, you should be very careful and then take some measures to protect yourself. For one thing, it is irritant which may cause inflammation to the skin or other mucous membranes, and it is irritating to rritating to eyes, respiratory system and skin. For another thing, it is harmful that may cause damage to health. If by inhalation, in contact with skin and if swallowed, it will be dangerous. Then it will have possible risk of harm to the unborn child. Therefore, you should take the following instructions. Wear suitable protective clothing, gloves and eye/face protection, and if in case of contact with eyes, rinse immediately with plenty of water and seek medical advice. Do remember not to breathe dust and if contacting with this chemical, take off immediately all contaminated clothing.

Additionally, you could convert the following datas into the molecular structure:
(1)Canonical SMILES: CC(C)C(=O)NC1=CC(=C(C=C1)[N+](=O)[O-])C(F)(F)F
(2)InChI: InChI=1S/C11H11F3N2O3/c1-6(2)10(17)15-7-3-4-9(16(18)19)8(5-7)11(12,13)14/h3-6H,1-2H3,(H,15,17)
(3)InChIKey: MKXKFYHWDHIYRV-UHFFFAOYSA-N?

Below are the toxicity information of this chemical:

Organism	Test Type	Route	Reported Dose (Normalized Dose)	Effect	Source
dog	LD50	oral	> 2gm/kg (2000mg/kg)	GASTROINTESTINAL: NAUSEA OR VOMITING GASTROINTESTINAL: OTHER CHANGES LIVER: OTHER CHANGES	Oyo Yakuri. Pharmacometrics. Vol. 45, Pg. 135, 1993.
man	TDLo	oral	310mg/kg/31D- (310mg/kg)	BEHAVIORAL: EUPHORIA	American Journal of Psychiatry. Vol. 143, Pg. 1498, 1986. ?
rat	LD50	intraperitoneal	289mg/kg (289mg/kg)	BEHAVIORAL: ALTERED SLEEP TIME (INCLUDING CHANGE IN RIGHTING REFLEX) LUNGS, THORAX, OR RESPIRATION: CYANOSIS	Oyo Yakuri. Pharmacometrics. Vol. 45, Pg. 135, 1993.
rat	LD50	oral	787mg/kg (787mg/kg)	KIDNEY, URETER, AND BLADDER: HEMATURIA KIDNEY, URETER, AND BLADDER: INCONTINENCE	Oyo Yakuri. Pharmacometrics. Vol. 45, Pg. 135, 1993.

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4.2 Specification

The Flutamide, with the cas registry number 13311-84-7, has the IUPAC name of 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide. Being a kind of light yellow solid, it is nearly insoluble in water, and it is usually used as the Antiandrogen and antineoplastic (hormonal). Besides, its product categories are including Aromatic Carboxylic Acids, Amides, Anilides, Anhydrides & Salts; APIs; Antitumors for Research and Experimental Use; Biochemistry; Amines; Aromatics; Intermediates & Fine Chemicals; Pharmaceuticals; API's.

The characteristics of this chemical are as follows: (1)ACD/LogP: 3.72; (2)# of Rule of 5 Violations: 0; (3)ACD/LogD (pH 5.5): 3.72; (4)ACD/LogD (pH 7.4): 3.72; (5)ACD/BCF (pH 5.5): 392.97; (6)ACD/BCF (pH 7.4): 392.97; (7)ACD/KOC (pH 5.5): 2504.06; (8)ACD/KOC (pH 7.4): 2504.05; (9)#H bond acceptors: 5; (10)#H bond donors: 1; (11)#Freely Rotating Bonds: 3; (12)Polar Surface Area: 66.13; (13)Index of Refraction: 1.52; (14)Molar Refractivity: 61.27 cm³; (15)Molar Volume: 201.2 cm³; (16)Polarizability: 24.29 ×10^-24 cm³; (17)Surface Tension: 38.2 dyne/cm; (18)Density: 1.372 g/cm³; (19)Flash Point: 195.9 °C; (20)Enthalpy of Vaporization: 65.11 kJ/mol; (21)Boiling Point: 400.3 °C at 760 mmHg; (22)Vapour Pressure: 1.29E-06 mmHg at 25°C; (23)Exact Mass: 276.072177; (24)MonoIsotopic Mass: 276.072177; (25)Topological Polar Surface Area: 74.9; (26)Heavy Atom Count: 19; (27)Formal Charge: 0; (28)Complexity: 352.

The production method of this chemical is as below: After the nitrification of benzenyl trifluoride to have m-nitrotrifluorinemethylbenzene, and then restore to have m-trifluorinemethylaniline; Next react with iso-butyryl chloride and then go through the nitrification to produce Flutamide.?

As to its usage, it is widely applied in many ways. It could be used as the NAISD male sex hormone antagonist which could restrain teststrone transforming into dihydro-testosterone; It could also be used in curing the diseases of PCa(prostatic cancer) and prostatic hyperplasia.

When you are dealing with this chemical, you should be very careful and then take some measures to protect yourself. For one thing, it is irritant which may cause inflammation to the skin or other mucous membranes, and it is irritating to rritating to eyes, respiratory system and skin. For another thing, it is harmful that may cause damage to health. If by inhalation, in contact with skin and if swallowed, it will be dangerous. Then it will have possible risk of harm to the unborn child. Therefore, you should take the following instructions. Wear suitable protective clothing, gloves and eye/face protection, and if in case of contact with eyes, rinse immediately with plenty of water and seek medical advice. Do remember not to breathe dust and if contacting with this chemical, take off immediately all contaminated clothing.

Additionally, you could convert the following datas into the molecular structure:
(1)Canonical SMILES: CC(C)C(=O)NC1=CC(=C(C=C1)[N+](=O)[O-])C(F)(F)F
(2)InChI: InChI=1S/C11H11F3N2O3/c1-6(2)10(17)15-7-3-4-9(16(18)19)8(5-7)11(12,13)14/h3-6H,1-2H3,(H,15,17)
(3)InChIKey: MKXKFYHWDHIYRV-UHFFFAOYSA-N?

Below are the toxicity information of this chemical:

Organism	Test Type	Route	Reported Dose (Normalized Dose)	Effect	Source
dog	LD50	oral	> 2gm/kg (2000mg/kg)	GASTROINTESTINAL: NAUSEA OR VOMITING GASTROINTESTINAL: OTHER CHANGES LIVER: OTHER CHANGES	Oyo Yakuri. Pharmacometrics. Vol. 45, Pg. 135, 1993.
man	TDLo	oral	310mg/kg/31D- (310mg/kg)	BEHAVIORAL: EUPHORIA	American Journal of Psychiatry. Vol. 143, Pg. 1498, 1986. ?
rat	LD50	intraperitoneal	289mg/kg (289mg/kg)	BEHAVIORAL: ALTERED SLEEP TIME (INCLUDING CHANGE IN RIGHTING REFLEX) LUNGS, THORAX, OR RESPIRATION: CYANOSIS	Oyo Yakuri. Pharmacometrics. Vol. 45, Pg. 135, 1993.
rat	LD50	oral	787mg/kg (787mg/kg)	KIDNEY, URETER, AND BLADDER: HEMATURIA KIDNEY, URETER, AND BLADDER: INCONTINENCE	Oyo Yakuri. Pharmacometrics. Vol. 45, Pg. 135, 1993.

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4.3 Toxicity

CHEMICAL IDENTIFICATION

RTECS NUMBER :: UG5700000

CHEMICAL NAME :: m-Propionotoluidide, 2-methyl-4'-nitro-alpha,alpha,alpha-triflouro-

CAS REGISTRY NUMBER :: 13311-84-7

LAST UPDATED :: 199806

DATA ITEMS CITED :: 27

MOLECULAR FORMULA :: C11-H11-F3-N2-O3

MOLECULAR WEIGHT :: 276.24

WISWESSER LINE NOTATION :: FXFFR BNW EMVY1&1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 310 mg/kg/31D-I

TOXIC EFFECTS :: Behavioral - euphoria

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 787 mg/kg

TOXIC EFFECTS :: Kidney, Ureter, Bladder - hematuria Kidney, Ureter, Bladder - incontinence Nutritional and Gross Metabolic - body temperature decrease

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 289 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Lungs, Thorax, or Respiration - cyanosis Nutritional and Gross Metabolic - body temperature decrease

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >2 gm/kg

TOXIC EFFECTS :: Gastrointestinal - nausea or vomiting Gastrointestinal - other changes Liver - other changes

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 700 mg/kg/28D-I

TOXIC EFFECTS :: Endocrine - androgenic Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 27300 mg/kg/52W-I

TOXIC EFFECTS :: Blood - pigmented or nucleated red blood cells Biochemical - Metabolism (Intermediary) - other proteins Related to Chronic Data - changes in prostate weight

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2730 mg/kg/1Y-I

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Reproductive - Tumorigenic effects - testicular tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1050 mg/kg

SEX/DURATION :: female 14-20 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 150 mg/kg

SEX/DURATION :: male 30 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 375 mg/kg

SEX/DURATION :: male 15 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 3840 mg/kg

SEX/DURATION :: male 64 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 280 mg/kg

SEX/DURATION :: male 7 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 525 mg/kg

SEX/DURATION :: female 14-20 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - skin and skin appendages Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 275 mg/kg

SEX/DURATION :: female 11-21 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 70 mg/kg

SEX/DURATION :: male 7 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - other effects on male

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 400 mg/kg

SEX/DURATION :: female 16-19 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - endocrine system Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intramuscular

DOSE :: 65 mg/kg

SEX/DURATION :: female 10-22 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - delayed effects

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intramuscular

DOSE :: 29040 ug/kg

SEX/DURATION :: male 17 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Parenteral

DOSE :: 350 mg/kg

SEX/DURATION :: male 7 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands Reproductive - Paternal Effects - other effects on male

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Parenteral

DOSE :: 200 mg/kg

SEX/DURATION :: female 16-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Paternal Effects - other effects on male Endocrine - androgenic

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 80 mg/kg

SEX/DURATION :: male 10 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 400 mg/kg

SEX/DURATION :: male 10 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 1 gm/kg

SEX/DURATION :: female 13-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - other postnatal measures or effects

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 300 mg/kg

SEX/DURATION :: female 14-16 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1225 mg/kg

SEX/DURATION :: female 6 week(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - other effects to embryo

MUTATION DATA

TYPE OF TEST :: DNA inhibition

TEST SYSTEM :: Rodent - rat Liver

DOSE/DURATION :: 50 umol/L

REFERENCE :: CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980- Volume(issue)/page/year: 13,373,1992

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5. MSDS

2.Hazard identification

2.1 Classification of the substance or mixture

Acute toxicity - Oral, Category 4

Acute toxicity - Dermal, Category 4

Acute toxicity - Inhalation, Category 4

Reproductive toxicity, Category 2

2.2 GHS label elements, including precautionary statements

Pictogram(s)
Signal word	Warning
Hazard statement(s)	H302 Harmful if swallowed H312 Harmful in contact with skin H332 Harmful if inhaled H361 Suspected of damaging fertility or the unborn child
Precautionary statement(s)
Prevention	P264 Wash ... thoroughly after handling. P270 Do not eat, drink or smoke when using this product. P280 Wear protective gloves/protective clothing/eye protection/face protection. P261 Avoid breathing dust/fume/gas/mist/vapours/spray. P271 Use only outdoors or in a well-ventilated area. P201 Obtain special instructions before use. P202 Do not handle until all safety precautions have been read and understood.
Response	P301+P312 IF SWALLOWED: Call a POISON CENTER/doctor/\u2026if you feel unwell. P330 Rinse mouth. P302+P352 IF ON SKIN: Wash with plenty of water/... P312 Call a POISON CENTER/doctor/\u2026if you feel unwell. P321 Specific treatment (see ... on this label). P362+P364 Take off contaminated clothing and wash it before reuse. P304+P340 IF INHALED: Remove person to fresh air and keep comfortable for breathing. P308+P313 IF exposed or concerned: Get medical advice/ attention.
Storage	P405 Store locked up.
Disposal	P501 Dispose of contents/container to ...

2.3 Other hazards which do not result in classification

none

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6. Synthesis Route

13311-84-7Total: 4 Synthesis Route

98-16-8 215 Suppliers

13311-84-7 247 Suppliers

Literatures:
Synthetic Communications, , vol. 36, # 7 p. 859 - 864
Yield: null

98-08-8 98 Suppliers

13311-84-7 247 Suppliers

Literatures:
Journal of Chemical Research, , vol. 38, # 4 p. 200 - 201
Yield: null

1939-27-1 19 Suppliers

13311-84-7 247 Suppliers

Literatures:
Bandgar; Sawant Synthetic Communications, 2006 , vol. 36, # 7 p. 859 - 864
Yield: ~79%

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7. Precursor and Product

precursor:

393-11-3

79-30-1

98-08-8

1939-27-1

98-16-8

product :

393-11-3

1579-89-1

39235-51-3

8. Other Information

8.0 Description: Flutamide is an orally active, non-steroidal antiandrogen indicated for the treatment of prostatic cancer in both castrates and noncastrates.

8.1 Originator: scheting (USA)

8.2 History: Flutamide was first described as a member of a series of N-acyl anilides synthesized at Monsanto in the 1960s during a compound finding program aiming at bacteriostatic agents. Soon after, at Schering Corp., the compound was characterized pharmacologically and further developed as SCH-13521. It was found that flutamide inhibits agonist action at the AR by replacing the agonist at the ligand binding site, being the first nonsteroidal compound possessing anti-androgenic activity in animals. In contrast to steroidal anti-androgens, for instance, cyproterone acetate, which also displays significant progestational activity, flutamide has no other hormonal activity. There is also no reduction of serum testosterone levels seen with flutamide but rather a slight increase in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) resulting in elevated serum testosterone levels. This accounts for the beneficial maintenance of libido and potency in sexually active patients. On the other hand, elevated serum estradiol levels resulting from peripheral testosterone aromatization leading to gynecomastia were observed in patients.

8.3 Uses: 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.

8.4 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.

8.5 Indications: 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.

8.6 Indications: 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.

8.7 Manufacturing Process: To a stirred, cooled solution of 100 g of 4-nitro-3-trifluoromethylaniline in 400 ml of pyridine, slowly and in a dropwise fashion, add 54 g of isobutyrylchloride and then heat the reaction mixture on a steam bath for 1.5 hours. Cool and pour the resulting mixture into ice water, filter and waterwash the crude anilide and crystallize the product of this example from benzene to obtain analytically pure material, MP 111.5°C to 112.5°C.

8.8 Brand name: Eulexin (Schering);DROGENIL.

8.9 General Description: Flutamide, 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide, is dosed 3 times daily(250-mg dose; 750-mg total daily dose). A major metaboliteof flutamide, hydroxyflutamide, is a more potent AR antagonistthan the parent compound. This metabolite, which ispresent at a much higher steady-state concentration than isflutamide, contributes a significant amount of the antiandrogen action of this drug. A limiting factor in the useof flutamide is hepatotoxicity in from 1% to 5% of patients.Although the hepatotoxicity usually is reversible followingcessation of treatment, rare cases of death associated withhepatic failure have been reported to be associated with flutamidetherapy. Diarrhea is also a limiting side effect withflutamide therapy for some patients.

8.10 Biochem/physiol Actions: Flutamide is a non-steroidal anti-androgen drug. It consists of a nitroaromatic structure. Flutamide is a potent competitor of testosterone and dihydrotestosterone receptors. It is a potent hepatotoxin.

8.11 Mechanism of action: Flutamide is a nonsteroid drug that possesses antiandrogenic action. It blocks androgens from binding with target tissues, thus preventing androgen action. The mechanism of action is possibly also linked with a halt in dihydrotestosterone transport. It facilitates a reduction in size and density of the prostate gland, and it reduces the amount of metastases in such cancer, for which it is used in palliative treatment of prostate gland cancer.

8.12 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.

8.13 Chemical Synthesis: Flutamide, 4-nitro-3-trifluoromethylisobutyranilide (29.2.15), a nonsteroid antagonist of androgens, is made by acylating 4-nitro-3-trifluoromethylaniline with isobutyric acid chloride.

8.14 Merck: 14,4208

8.15 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.

8.16 References: https://en.wikipedia.org/wiki/Flutamide
https://pubchem.ncbi.nlm.nih.gov/compound/flutamide#section=Top

8.17 Chemical Properties: Light Yellow Solid

8.18 Uses: neuroleptic

8.19 Uses: Flutamide is a nonsteroidal antiandrogen drug; antineoplastic (hormonal).

8.20 Uses: Antiandrogen; antineoplastic (hormonal).

8.21 Brand name: Eulexin (Schering).

8.22 Contact allergens: Flutamide is an antiandrogenic hormonal antineoplas tic drug that can induce photosensitivity and porphy ria-like eruption.

9. Computational chemical data

Molecular Weight: 276.21185g/mol
Molecular Formula: C₁₁H₁₁F₃N₂O₃
Compound Is Canonicalized: True
XLogP3-AA: null
Exact Mass: 276.07217670
Monoisotopic Mass: 276.07217670
Complexity: 352
Rotatable Bond Count: 2
Hydrogen Bond Donor Count: 1
Hydrogen Bond Acceptor Count: 6
Topological Polar Surface Area: 74.9
Heavy Atom Count: 19
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Isotope Atom Count: 0
Covalently-Bonded Unit Count: 1
CACTVS Substructure Key Fingerprint: AAADccBzMYAAAAAAAAAAAAAAAAAAAAAAAAAwAAAAAAAAAAABAAAAHwAUAAAADQiBmBAywILQQACJAiVSUwCCAAAhAgAoiAEAZIoIICLAkZGEIAhglADIyAcQgAAOAACAQAACAAAAAQCAAAQAAAAAAAAAAA==

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