ニルタミド
アナンドロン · ニルタミド · 5,5-ジメチル-3-[4-ニトロ-3-(トリフルオロメチル)フェニル]ヒダントイン · 5,5-ジメチル-3-[4-ニトロ-3-(トリフルオロメチル)フェニル]-2,4-イミダゾリジンジオン · 5,5-ジメチル-3-[4-ニトロ-3-(トリフルオロメチル)フェニル]イミダゾリジン-2,4-ジオン · Nerumet · RU-23908 · ANANDRON
識別子と物理属性
| CAS No. | 63612-50-0 |
|---|---|
| 分子式 | C12H10F3N3O4 |
| 平均分子量 | 317.22 g/mol |
| 単同位体質量 | 317.06234046 g/mol |
| SMILES | CC1(C)NC(=O)N(c2ccc([N+](=O)[O-])c(C(F)(F)F)c2)C1=O |
| InChIKey | XWXYUMMDTVBTOU-UHFFFAOYSA-N |
| PubChem CID | 4493 |
| ChEMBL | CHEMBL1274 |
| ChEBI | CHEBI:7573 |
| EC No. | 624-700-6 |
| DTXSID | DTXSID3034165 |
| 現地名 | ニルタミド |
化学・物理的性質
| XLogP | 2 |
|---|---|
| 極性表面積 | 95.2 |
| 水素結合供与体数 | 1 |
| 水素結合受容体数 | 7 |
| 回転可能結合数 | 1 |
| 重原子数 | 22 |
| 形式電荷 | 0 |
| 複雑度 | 515 |
| 医薬品 | Pharmaceuticals -> Antineoplastic and immunomodulating agents -> Antineoplastic agentsPharmaceuticals -> Listed in ZINC15 |
| LogP（分配係数） | 1.8 |
| 溶解度 | 4.19e-03 g/L水に微溶、アセトンに易溶、無水エタノールに可溶。 |
| Human Drugs | FDA approved drugs -> Active ingredientHormones and antihormones |
| Endocrine Disruptors | Potential endocrine disrupting compound |
| Physical Description | Solid |
| Collision Cross Section | 162.8 Ų [M-H]- [CCS Type: DTBuffer gas: N2Ionization: ESI-Dataset: TOXCASTSource Identifier: DTXSID3034165] |
| 融点 | 1490C |
| 密度 | 1.463±0.06 g/cm3(Predicted) |
| 貯蔵条件 | Sealed in dry,Room Temperature |
| 外観・状態 | 個体 |
| pKa（酸解離定数） | 7.59±0.70(Predicted) |
| 色 | Light yellow to yellow |
| 主な用途 | 医薬品（低分子化合物） |
| InChI | InChI=1S/C12H10F3N3O4/c1-11(2)9(19)17(10(20)16-11)6-3-4-8(18(21)22)7(5-6)12(13,14)15/h3-5H,1-2H3,(H,16,20) |
| InChIKey | XWXYUMMDTVBTOU-UHFFFAOYSA-N |
| SMILES | C1(=O)NC(C)(C)C(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 |
| CAS データベース | 63612-50-0(CAS DataBase Reference) |
化学的特性
Crystalline Solid
安全性と法規制
| GHS 分類 | DangerH301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]P203, P264, P270, P280, P301+P316, P318, P321, P330, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 41 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Hazard Classes and Categories | Acute Tox. 3 (100%) |
| Hepatotoxicity | In large registration clinical trials, ALT elevations occurred in 8% (range 2% to 33%) of patients during nilutamide therapy. The elevations were usually mild, asymptomatic and transient, requiring drug discontinuation in only 1% of treated patients. In rare instances, clinically apparent acute liver injury has occurred during nilutamide therapy, but the number of published cases are few, and the agent appears to be less hepatotoxic than flutamide. Nevertheless, fatal cases have been reported (Case 1). In reported cases, the latency to onset averaged 2 to 4 months and the clinical pattern of enzyme elevations was typically hepatocellular, thus largely resembling flutamide induced liver injury. Signs of hypersensitivity and autoimmunity were not common. |
| 暴露経路 | Rapidly and completely absorbed, yielding high and persistent plasma concentrations. |
| 毒性の概要 | Nilutamide competes with androgen for the binding of androgen receptors, consequently blocking the action of androgens of adrenal and testicular origin that stimulate the growth of normal and malignant prostatic tissue. This blockade of androgen receptors may result in growth arrest or transient tumor regression through inhibition of androgen-dependent DNA and protein synthesis. |
| Signs and Symptoms | Symptoms of overdose include dizziness, general discomfort, headache, nausea, and vomiting. |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)NilutamidevMost-DILI-concern8Warnings & precautionsDOI:10.1016/j.drudis.2016.02.015 |
| 水環境危害等級（WGK） |
用途
説明
Nilutamide is a non-steroidal anti-androgen similar in potency to the acyclic urea flutamide (55) and useful in the management of prostatic carcinoma.
来歴
The second nonsteroidal anti-androgen to be marketed was nilutamide. It was discovered from a series of flutamide analogues at Roussel Uclaf (now Sanofi) in the 1970s using a rat prostate assay determining the inhibition of androgen uptake.The investigational compound code was RU 23908. Its structure is closely related to hydroxyflutamide, particularly under the assumption that the α-hydroxyamide engages in an internal hydrogen bond when bound to the AR LBD. The hydantoin moiety of nilutamide mimics the active conformation of hydroxyflutamide. Like flutamide, nilutamide blocks the action of androgens originating from both testis and adrenal. It also has neither agonist nor any other hormonal activity. Nilutamide has an elimination half-life of approximately 2 days in patients, which is significantly longer than that of flutamide. Thus, a single oral dose of 150 mg daily was feasible.
使用
Nonsteroidal antiandrogen. Antineoplastic (hormonal)
一般的な説明
Nilutamide, 5,5-dimethyl-3-[4-nitro-3-(trifluoromethyl)phenyl]-2,4-imidazolidinedione, is usedin combination with surgical castration for the treatment ofmetastatic prostate cancer. Nilutamide, which has an eliminationhalf-life of approximately 40 hours, can also be usedin once-daily dosing, but it has side effects that limit itsuse—visual disturbances, alcohol intolerance, and allergicpneumonitis.