フルタミド
フルタミド · ドロゲニル · 2-メチル-N-(4-ニトロ-3-トリフルオロメチルフェニル)プロピオンアミド · ニフトリド · N-[3-(トリフルオロメチル)-4-ニトロフェニル]イソブチルアミド · オイレキシン【抗ホルモン】 · 2-メチル-N-[4-ニトロ-3-(トリフルオロメチル)フェニル]プロパンアミド · N-[3-(トリフルオロメチル)-4-ニトロフェニル]-2-メチルプロパンアミド
識別子と物理属性
| CAS No. | 13311-84-7 |
|---|---|
| 分子式 | C11H11F3N2O3 |
| 平均分子量 | 276.21 g/mol |
| 単同位体質量 | 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 |
| 現地名 | フルタミド |
化学・物理的性質
| XLogP | 3.3 |
|---|---|
| 極性表面積 | 74.9 |
| 水素結合供与体数 | 1 |
| 水素結合受容体数 | 6 |
| 回転可能結合数 | 2 |
| 重原子数 | 19 |
| 形式電荷 | 0 |
| 複雑度 | 352 |
| 医薬品 | PharmaceuticalsPharmaceuticals -> Antineoplastic and immunomodulating agents -> Antineoplastic agentsPharmaceuticals -> Listed in ZINC15 |
| LogP（分配係数） | 2.6 |
| 溶解度 | 5.66e-03 g/L>41.4 [ug/mL] (The mean of the results at pH 7.4)水にほとんど溶けず、アセトンとエタノールに溶けやすい (96%)。 |
| Human Drugs | FDA approved drugs -> Active ingredientHormones and antihormones |
| Endocrine Disruptors | Potential endocrine disrupting compound |
| 融点 | 111.5-112.5111 - 113 °C112 °C |
| Physical Description | Solid |
| Collision Cross Section | 154.9 Ų [M-H]- [CCS Type: DTBuffer gas: N2Ionization: ESI-Dataset: TOXCASTSource Identifier: DTXSID7032004]160 Ų [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]154.25 Ų [M+H-H2O]+ [CCS Type: TW |
| 沸点 | 400.3±45.0 °C(Predicted) |
| 密度 | 1.3649 (estimate) |
| 貯蔵条件 | 2-8°C |
| 外観・状態 | Solid |
| pKa（酸解離定数） | 13.12±0.70(Predicted) |
| 色 | 淡黄色～淡黄色 |
| Merck | 14,4208 |
| 主な用途 | 医薬品（低分子化合物） |
| 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 データベース | 13311-84-7(CAS DataBase Reference) |
| EPAの化学物質情報 | Flutamide (13311-84-7) |
化学的特性
Light Yellow Solid
安全性と法規制
| GHS 分類 | 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] |
|---|---|
| 規制情報 | 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). |
| 有害作用 | 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. |
| 暴露経路 | Rapidly and completely absorbed. |
| 毒性の概要 | 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 |
| 水環境危害等級（WGK） | 3 |
| RTECS 番号 | UG5700000 |
| 輸送番号（UN） | UN3077 |
| 税関コード | 29242990 |
| 危険文句（R） | 20/21/22-63-36/37/38 |
| 危険表示 | Xn,Xi |
| 安全措置（S） | 22-36-36/37/39-27-26 |
| 危険等級 | 9Acute Tox. 4 OralAquatic Chronic 2Carc. 2Repr. 2STOT RE 2 |
| 貯蔵分類 | 11 - Combustible Solids |
用途
用途
非ステロイド性抗アンドロゲ ン作用を持ちます。アンドロゲン受容体への アンドロゲンの結合を阻害します。
用途
医薬(抗アンドロゲン剤)
用途
がん研究用試薬
説明
Flutamide is an orally active, non-steroidal antiandrogen indicated for the treatment of prostatic cancer in both castrates and noncastrates.
来歴
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.
使用
Flutamide is a nonsteroidal antiandrogen drug; antineoplastic (hormonal).
一般的な説明
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.