Nilutamide

Nilutamide 속성

Nilutamide MSDS

5,5-Dimethyl-3-[4-nitro-3-(trifluoromethyl)phenyl]-2,4-imidazolidinedione

Nilutamide C화학적 특성, 용도, 생산

개요

Nilutamide is a non-steroidal anti-androgen similar in potency to the acyclic urea flutamide (55) and useful in the management of prostatic carcinoma.

화학적 성질

Crystalline Solid

역사

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.

용도

Nonsteroidal antiandrogen. Antineoplastic (hormonal)

Indications

Clinical trials with nilutamide were conducted predominantly in combination with orchiectomy. Results indicated retardation of disease progression and relief of metastatic bone pain in patientswith advanced prostate cancer.However, patient survival benefit was small compared with castration alone. Studies of nilutamide monotherapy or combination with LHRH agonists did not have sufficient patient numbers to allow reliable conclusions on efficacy. Nilutamide was first launched in France in 1987 for treatment of metastatic prostate cancer in adjuvant therapy with surgical castration. Approval in several major markets was granted in the following years.
The tolerability profile of nilutamide was similar to that of flutamide. Hot flushes, nausea, diarrhea, constipation, gastrointestinal pain, abnormal liver function, and gynecomastia were frequently reported adverse events with both drugs. Additional side effects were predominantly associated with nilutamide treatment: interstitial pneumonitis, impaired adaptation to darkness, and alcohol intolerance.
The nonsteroidal anti-androgens flutamide and nilutamide established combined androgen blockade as first-line treatment for metastatic prostate cancer. Still, there was room for improvement with regard to overall survival (OS) and tolerability.

일반 설명

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.

생물학적 활성

Non-steroidal and silent antiandrogen. Binds to androgen receptors and also inhibits androgen biosynthesis in vitro . In rats in vivo it inhibits androgen-induced prostate weight increase and inhibits negative androgen-dependent gonadotropin feedback leading to an increase in luteinising hormone and testosterone. Orally active.

Mechanism of action

The therapeutic effects of nilutamide are overshadowed, however, by the occurrence of several adverse reactions mediated by toxic mechanisms, which are poorly investigated. The reduction of nilutamide is catalyzed by NO synthases via the formation of either or both a nitro anion free radical or its reduction to its hydroxylamino derivative could explain some of the toxic effects of this drug. Nitric oxide synthases also are involved in the formation of reactive NO and oxygen species and in the interactions with some xenobiotic compounds.

Clinical Use

Nilutamide is a hepatotoxic nitroaromatic antiandrogen used for the treatment of metastatic prostate carcinoma in men.

신진 대사

Nilutamide is a nitroaromatic hydantoin analog of flutamide, that is completely absorbed after oral administration, with a mean elimination half-life of approximately 50 hours. One of the methyl groups attached to the hydantoin ring is stereoselectively hydroxylated to a chiral metabolite, which subsequently is oxidized to its carboxylic acid metabolite. Less than 2% of nilutamide is excreted unchanged in the urine. In vitro, the nitro group of nilutamide was reduced to the amine and hydroxylamine moieties by nitric oxide (NO) synthases, a flavin monooxygenase (FMO) system.

Nilutamide 준비 용품 및 원자재

원자재

준비 용품

Nilutamide 공급 업체

공급자	전화	이메일	국가	제품 수	이점
Capot Chemical Co.,Ltd.	571-85586718 +8613336195806	sales@capotchem.com	China	29797	60
career henan chemical co	+86-0371-86658258	sales@coreychem.com	China	29914	58
SHANDONG ZHI SHANG CHEMICAL CO.LTD	+86 18953170293	sales@sdzschem.com	China	2931	58
BOC Sciences	+1-631-485-4226	inquiry@bocsci.com	United States	19553	58
Alchem Pharmtech,Inc.	8485655694	sales@alchempharmtech.com	United States	63711	58
CONIER CHEM AND PHARMA LIMITED	+8618523575427	sales@conier.com	China	47465	58
Shaanxi Dideu Medichem Co. Ltd	+86-29-87569266 15319487004	1015@dideu.com	China	2263	58
TargetMol Chemicals Inc.	+1-781-999-5354 +1-00000000000	marketing@targetmol.com	United States	19892	58
Dideu Industries Group Limited	+86-29-89586680 +86-15129568250	1026@dideu.com	China	29474	58
AFINE CHEMICALS LIMITED	0571-85134551	info@afinechem.com	CHINA	15377	58

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