플루타마이드
플루타마이드 · Eunex · Odyne · Euflex · Drognil · Eulexin · Fugerel · Drogenil
식별자 및 물리적 특성
| CAS No. | 13311-84-7 |
|---|---|
| 분자식 | C11H11F3N2O3 |
| 평균 분자량 | 276.21 g/mol |
| 단동위원소 질량 | 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 |
| 현지명 | 플루타마이드 |
화학 및 물리적 성질
| XLogP | 3.3 |
|---|---|
| 극성 표면적 | 74.9 |
| 수소 결합 공여자 수 | 1 |
| 수소 결합 수용자 수 | 6 |
| 회전 가능 결합 수 | 2 |
| 무거운 원자 수 | 19 |
| 형식 전하 | 0 |
| 복잡도 | 352 |
| 의약품 | PharmaceuticalsPharmaceuticals -> Antineoplastic and immunomodulating agents -> Antineoplastic agentsPharmaceuticals -> Listed in ZINC15 |
| LogP(분배 계수) | 2.6 |
| 용해도 | 5.66e-03 g/L>41.4 [ug/mL] (The mean of the results at pH 7.4)물에는 거의 녹지 않으며, 아세톤과 에탄올(96%)에는 잘 녹습니다. |
| Human Drugs | FDA approved drugs -> Active ingredientHormones and antihormones |
| Endocrine Disruptors | Potential endocrine disrupting compound |
| 녹는점 | 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 |
| 끓는 점 | 400.3±45.0 °C(Predicted) |
| 밀도 | 1.3649 (estimate) |
| 저장 조건 | 2-8°C |
| 물리적 상태 | Solid |
| pKa(산도 계수) | 13.12±0.70(Predicted) |
| 색상 | 연한 노란색에서 밝은 노란색까지 |
| Merck | 14,4208 |
| 주요 응용 | 의약품(소분자) |
| 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 |
| EPA | Flutamide (13311-84-7) |
화학적 성질
Light Yellow Solid
안전 및 규제
| GHS 분류 | 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] |
|---|---|
| 규제 정보 | 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). |
| 유해 작용 | 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. |
| 노출 경로 | Rapidly and completely absorbed. |
| 독성 요약 | 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 |
| 수질 위해 등급(WGK) | 3 |
| RTECS 번호 | UG5700000 |
| 운송 번호(UN) | UN3077 |
| 관세 코드 | 29242990 |
| 위험 문구(R) | 20/21/22-63-36/37/38 |
| 위험 표시 | Xn,Xi |
| 안전 문구(S) | 22-36-36/37/39-27-26 |
| 위험 등급 | 9Acute Tox. 4 OralAquatic Chronic 2Carc. 2Repr. 2STOT RE 2 |
| 저장 분류 | 11 - Combustible Solids |
용도
개요
Flutamide is an orally active, non-steroidal antiandrogen indicated for the treatment of prostatic cancer in both castrates and noncastrates.
역사
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.
용도
Flutamide is a nonsteroidal antiandrogen drug; antineoplastic (hormonal).
일반 설명
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.