Febuxostat

Febuxostat 속성

Febuxostat C화학적 특성, 용도, 생산

개요

Febuxostat, a selective xanthine oxidase inhibitor, was launched for the chronic management of hyperuricemia in patients with gout. Hyperuricemia is defined as a serum uric acid concentration exceeding the limit of solubility. It predisposes affected persons to gout, a disease characterized by the formation of crystals of monosodium urate or uric acid from supersaturated fluids in joints and other tissues. Crystal deposition is asymptomatic, but it is revealed by bouts of joint inflammation. If left untreated, further crystals accumulate in joints and can form deposits known as tophi. A major aim in gout management is the long-term reduction of serum uric acid concentrations below saturation levels, as this results in crystal dissolution and eventual disappearance.
Febuxostat is a nonpurine derivative with higher potency and selectivity than allopurinol for inhibiting xanthine oxidase. It completely inhibits human xanthine oxidase activity in the lung cancer cell line A549, whereas the activities of other enzymes involved in purine or pyrimidine metabolism (e.g., purine nucleoside phosphorylase, adenosine deaminase, and pyrimidine nucleoside phosphorylase) are affected by<4%.

화학적 성질

Crystalline Solid

물리적 성질

Febuxostat has low solubility. It is almost insoluble in acidic conditions, slightly soluble in neutral conditions, and slightly more soluble in alkaline conditions. It is not suitable for making injections, but it can be taken orally because of its high oil-water partition coefficient and strong ability to cross cell membranes.

용도

Febuxostat is a new generation xanthine oxidase inhibitor developed by Tejin Co. (Japan,) used clinically for for long-term treatment of hyperuicemia (gout,) a new and highly effective non-purine selective inhibitor of xanthine oxidase. 40-120 mg/day febuxostat was proven effective in lowering serum urate levels when administered to manage hyperuricemia in patients with gout. It is not recommended for gout patients without hyperuricemia.

제조 방법

Febuxostat can be synthesized in a multistep sequence from 2,4-dicyanophenol, starting with the alkylation of the phenolic hydroxyl group with isobutyl bromide and potassium carbonate, followed by treatment with thioacetamide in hot dimethyl formamide to yield 3-cyano-4-isobutoxythiobenzamide. Cyclization of the thioamide group with 2-chloroacetoacetic acid ethyl ester in refluxing ethanol affords 2-(3-cyano-4-isoutoxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester, which is hydrolyzed with sodium hydroxide to produce febuxostat.

일반 설명

Febuxostat is a potent, non-purine compound, which inhibits the expression of cytokines/chemokines. It has also been reported to inhibit LPS-induced TNF-α, VCAM-1, MMP9 and MCP-1 expression.

Clinical Use

Fabuxostat was discovered by Teijin Pharmaceuticals and licensed to TAP Pharmaceuticals (which is currently part of Takeda Pharmaceuticals) and was approved in the U.S. for the treatment of hyperuricemia in patients with gout. It is a once-daily non-purine based agent with potent inhibitory activity against xanthine oxidase. The safety profile of the drug also does not require dose adjustment for patients with mild to moderate renal or hepatic impairment. Febuxostat is the first new agent cleared for this indication in 40 years.

부작용

The incidence of adverse events such as dizziness, diarrhea, headache, and nausea with febuxostat was similar to allopurinol. Febuxostat is contraindicated in patients being treated with the xanthine oxidase substrates such as azathioprine, mercaptopurine, and theophylline.

Mode of action

Xanthine oxidase is the main enzyme promoting uric acid production. It works by non-competitively blocking the molybdenum pterin center, which is the active site of xanthine oxidase. Through highly selective inhibition of oxidized and reduced xanthine oxidase, Febuxostat can reduce the synthesis of uric acid, decreasing its concentration and effectively treating gout. Through liver metabolism, Xanthine oxidase does not rely on renal excretion, so patients with moderate to severe liver and kidney dysfunction do not need to reduce dosages. Febuxostat is a non-purine XOR inhibitor, so it is very safe.

Febuxostat 준비 용품 및 원자재

원자재

준비 용품

Febuxostat 공급 업체

공급자	전화	이메일	국가	제품 수	이점
SHANDONG BOYUAN PHARMACEUTICAL CO., LTD.	+86-0531-69954981 +8615666777973	dwyane.wang@boyuanpharm.com	China	211	58
shan dong Fengjin Pharmaceutical company	+8615066764791	liangfulin@fengjin-pharma.com	China	8	58
JUYE XIANDAI fine chemistry Co.,Ltd	+86-18958038633; +8618958038633	tony@sdhypharma.com	China	64	58
Hubei Chuyunshun Biotechnology Co., Ltd.	+86-15926415536 +86-15926415536	hbcyssw@163.com	China	160	58
Hebei Weibang Biotechnology Co., Ltd	+8615531157085	abby@weibangbio.com	China	8810	58
Hebei Mojin Biotechnology Co., Ltd	+86 13288715578 +8613288715578	sales@hbmojin.com	China	12839	58
Zibo Hangyu Biotechnology Development Co., Ltd	+86-0533-2185556 +8617865335152	Mandy@hangyubiotech.com	China	10986	58
Anhui Ruihan Technology Co., Ltd	+8617756083858	daisy@anhuiruihan.com	China	973	58
hebei hongtan Biotechnology Co., Ltd	+86-86-1913198-3935 +8617331935328	sales03@chemcn.cn	China	970	58
BEIJING SJAR TECHNOLOGY DEVELOPMENT CO., LTD.	+86-18600796368 +86-18600796368	sales@sjar-tech.com	China	444	58

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