Flutamid

Eunex · Odyne · Euflex · Drognil · Eulexin · Fugerel · Drogenil · Eu．1exim

Identifikatoren & physikalische Daten

CAS No.	13311-84-7
Summenformel	C11H11F3N2O3
Durchschnittliche Molmasse	276,21 g/mol
Monoisotopische Masse	276,07217687 g/mol
SMILES	CC(C)C(=O)Nc1ccc([N+](=O)[O-])c(C(F)(F)F)c1
InChIKey	MKXKFYHWDHIYRV-UHFFFAOYSA-N
PubChem CID	3397
ChEMBL	CHEMBL4759307
ChEBI	CHEBI:5132
EC No.	236-341-9
DTXSID	DTXSID7032004
Lokaler Name	Flutamid

Chemische & physikalische Eigenschaften

XLogP	3,3
Polarare Oberfläche (TPSA)	74,9
H-Brücken-Donoren	1
H-Brücken-Akzeptoren	6
Frei drehbare Bindungen	2
Schwere Atome	19
Formalladung	0
Komplexität	352
Arzneimittel	PharmaceuticalsPharmaceuticals -> Antineoplastic and immunomodulating agents -> Antineoplastic agentsPharmaceuticals -> Listed in ZINC15
LogP (Verteilungskoeffizient)	2.6
Löslichkeit	5.66e-03 g/L>41.4 [ug/mL] (The mean of the results at pH 7.4)Practically insoluble in water, freely soluble in acetone and in ethanol (96 per cent).
Human Drugs	FDA approved drugs -> Active ingredientHormones and antihormones
Endocrine Disruptors	Potential endocrine disrupting compound
Schmelzpunkt	111.5-112.5111 - 113 °C112 °C
Physical Description	Solid
Collision Cross Section	154.9 Å² [M-H]- [CCS Type: DTBuffer gas: N2Ionization: ESI-Dataset: TOXCASTSource Identifier: DTXSID7032004]160 Å² [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]154.25 Å² [M+H-H2O]+ [CCS Type: TW
Siedepunkt	400.3±45.0 °C(Predicted)
Dichte	1.3649 (estimate)
Lagerbedingungen	2-8°C
Aggregatzustand	Solid
pKa (Säurekonstante)	13.12±0.70(Predicted)
Farbe	Pale Yellow to Light Yellow
Merck	14,4208
Hauptanwendungen	pharmaceutical (small molecule)
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)
InChIKey	MKXKFYHWDHIYRV-UHFFFAOYSA-N
SMILES	C(NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1)(=O)C(C)C
CAS Datenbank	13311-84-7(CAS DataBase Reference)
EPA chemische Informationen	Flutamide (13311-84-7)

Sicherheit & Vorschriften

GHS-Einstufung	DangerH302+H312+H332 (29.8%): Harmful if swallowed, in contact with skin or if inhaled [Warning Acute toxicity, oralacute toxicity, dermalacute toxicity, inhalation]P203, P260, P261, P264, P270, P271, P273, P280, P301+P317, P302+P352, P304+P340, P317, P318, P319, P321, P330, P362+P364, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 94 reports by companies from 15 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.H361: Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]
Regulatorische Informationen	Hazard Traits - Developmental Toxicity
Hazard Classes and Categories	Acute Tox. 4 (88.3%)Reproductive toxicity - Category 2
Hepatotoxicity	Chronic therapy with flutamide is associated with elevations in serum aminotransferase levels in up to 62% of patients, but marked elevations (above 5 times ULN) in only 3% to 5%. Most of these abnormalities are transient, asymptomatic and do not require dose adjustment or drug discontinuation. However, in 0.1% to 1% of patients, acute liver injury with symptoms and jaundice arises which can be prolonged, severe and even fatal. The latency of onset ranges widely from 1 to 10 months (Cases 2 and 3), averaging 3 months. Allergic manifestations are rare as are autoantibodies. The pattern of liver enzyme elevations is most commonly hepatocellular, but many cases with cholestatic and mixed patterns have been described. Liver failure with a requirement for emergency liver transplantation or fatality has been described in many publications with 20 fatal cases reported from the FDA MedWatch program during the first 5 years of its availability. Fatal cases have been reported in children and young women being treated for hirsutism or acne (Case 1).
Unerwünschte Wirkungen	Flutamide comes with a black box warning due to the risk of hepatic failure. Hospitalization and death have occurred, although rarely, due to flutamide usethis is due to cholestatic hepatitis, which leads to failure. Cholestatic hepatitis results from the mitochondrial toxicity that occurs due to flutamide's major metabolite, hydroxyflutamide. This metabolite inhibits enzymes that are necessary for the electron transport chain within the mitochondria of the hepatocyte, leading to a halt of cellular respiration and, ultimately, cellular death. Hepatic failure would most likely be evident within the first three months of use. If the hepatic injury does occur in a patient, discontinuation of flutamide may help reverses the injury. Estimates of the rate at which this adverse effect occurs are three persons in 10,000 or 0.03% of all patients who use the drug. Due to this risk, it is advisable to perform liver function tests if symptoms suggest hepatic dysfunction. Such signs to watch for are abdominal pain, anorexia, nausea, vomiting, jaundice, and right upper quadrant pain and tenderness. Recommendations are to discontinue therapy if jaundice develops or if alanine aminotransferase increased to two times the upper limit of normal.
Expositionspfade	Rapidly and completely absorbed.
Toxizitätsübersicht	There is a risk for severe hepatic injury leading to hepatic failure. There is a potential for aniline toxicity, which may cause methemoglobinemia or hemolytic anemia. The risk of cardiovascular disease may increase due to androgen deprivation.Flutamide is a nonsteroidal antiandrogen that blocks the action of both endogenous and exogenous testosterone by binding to the androgen receptor. In addition Flutamide is a potent inhibitor of testosterone-stimulated prostatic DNA synthesis. Moreover, it is capable of inhibiting prostatic nuclear uptake of androgen.
Signs and Symptoms	In animal studies with flutamide alone, signs of overdose included hypoactivity, piloerection, slow respiration, ataxia, and/or lacrimation, anorexia, tranquilization, emesis, and methemoglobinemia.
Carcinogen Classification	No indication of carcinogenicity to humans (not listed by IARC).
Drug Induced Liver Injury	Drug Induced Liver Injury Rank (DILIrank 2.0)FlutamidevMost-DILI-concern8Box warningDOI:10.1016/j.drudis.2016.02.015
Wassergefährdungsklasse (WGK)	3
UN-Transportnummer	UN3077
Zollcode	29242990
RTECS-Nr.	UG5700000
R-Sätze (R)	20/21/22-63-36/37/38
Gefahrensymbole	Xn,Xi
Sicherheitshinweise (S)	22-36-36/37/39-27-26
Gefahrenklasse	9Acute Tox. 4 OralAquatic Chronic 2Carc. 2Repr. 2STOT RE 2
Lagerklasse	11 - Combustible Solids

Anwendungen & Verwendung

Beschreibung

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

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.

Verwenden

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