非罗考昔

中文名称:

非罗考昔

中文同义词:

非罗考昔溶液, 100PPM;3-(环丙基甲氧基)-5,5-二甲基-4-[4-(甲基磺酰基)苯基]-2(5H)-呋喃酮;非罗考昔

英文名称:

Firocoxib

英文同义词:

FIROCOXIB;2(5H)-Furanone, 3-(cyclopropylmethoxy)-5,5-dimethyl-4-4-(methylsulfonyl)phenyl-;3-(cyclopropylmethoxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2- one;3-(Cyclopropylmethoxy)-5,5-dimethyl-4-[4-(methylsulfonyl)phenyl]-2(5H)-furanone;Equioxx;Equixx;Librens;ML 1785713

CAS号:

189954-96-9

分子式:

C17H20O5S

分子量:

336.4

EINECS号:

200-001-2

相关类别:

信号转导通路激酶抑制剂;化工中间体;兽药原料药;兽药原料;医用原料;原料药;THIOCYMETIN;Aromatics;Heterocycles;Intermediates Fine Chemicals;Pharmaceuticals;Sulfur Selenium Compounds

Mol文件:

189954-96-9.mol

熔点 

78-80°C

沸点 

563.9±50.0 °C(Predicted)

密度 

1.31

储存条件 

-20?C Freezer

概述

非罗考昔是一种重要的非甾体抗炎兽用药物，其作用主要是通过选择性抑制环氧化酶-2(COX-2)介导的前列腺素的合成，以阻断花生四烯酸转化为前列腺素，进而产生解热、镇痛和抗炎的功效。与其他非甾体抗炎兽用药物相比，非罗考昔能够高效地选择性地抑制COX-2，并能够迅速被机体吸收，对缓解骨关节炎疼痛有显著疗效。

制备方法

以化合物A为起始原料，与乙酰氧基乙酰氯反应生成化合物B；化合物B加入DBU，于80℃至少反应18h，得到化合物C；化合物C再在溶剂DMF中，NaH做碱的条件下与环丙基溴甲烷反应生成非罗考昔。反应式如下：

精制提纯

将20g纯度为98.2％非罗考昔粗品加入100g乙醇-纯化水混合液(乙醇与纯化水的质量比为1：1)中，加热至60℃左右固体非罗考昔粗品完全溶解，加入2g活性炭，于60℃左右继续搅拌30min；将上述混合液过滤，得到的母液在搅拌条件下自然降温，稍微降温后析出 固体，继续将上述料液温度冷却至0～5℃保温30min使结晶完全，抽滤，50℃真空干燥干燥得16.2g白色的非罗考昔固体粉末，HPLC纯度99.5％，精制率81％。

生物活性

Firocoxib (ML 1785713) 是一种有效的，选择性的，口服活性的 COX-2 抑制剂，IC50 为 0.13 μM。Firocoxib 对 COX-2 的选择性比对 COX-1 的选择性高 58 倍 (IC50 为 7.5 μM)。Firocoxib 具有抗炎作用。

靶点

COX-2 0.13 μM (IC 50 ) COX-1 7.5 μM (IC 50 )

COX-2 0.13 μM (IC 50 )

COX-1 7.5 μM (IC 50 )

体外研究

The COX-1:COX-2 selectivity ratios generally are established by comparing the IC 50 for COX-1 to the IC 50 for COX-2. The IC 80 value more closely resembles the steady-state plasma drug concentration than does the IC 50 value.The selectivity ratio for Firocoxib based on the IC 80 values is 121 (IC 80 of 0.36 μM and 43.6 μM for COX-2 and COX-1, respectively), indicating that selectivity for COX-2 is not reduced at concentrations higher than the IC 50 . Notably, Firocoxib concentrations that yield 80% to 95% inhibition of COX-2 produce < 20% inhibition of COX-1.

体内研究

Firocoxib (0.75-1.5mg/kg; oral gavage; female domestic shorthair cats) treatment efficacious in attenuating fever when administered to cats 1 or 14 hours before LPS challenge. Pharmacokinetic properties of Firocoxib are determined after i.v. (2 mg/kg) and oral (3 mg/kg) administration in male cats. Firocoxib has moderate to high oral bioavailability (54% to 70%), low plasma clearance (4.7 to 5.8 mL/min/kg), and an elimination half-life of 8.7 to 12.2 hours. Animal Model: 14 healthy female domestic shorthair cats (11-15 months old, 2.9-3.9 kg) with lipopolysaccharide (LPS) Dosage: 0.75 mg/kg, 1.5 mg/kg Administration: Oral gavage Result: Was efficacious in attenuating fever when administered to cats 1 or 14 hours before LPS challenge.

Animal Model:

14 healthy female domestic shorthair cats (11-15 months old, 2.9-3.9 kg) with lipopolysaccharide (LPS)

Dosage:

0.75 mg/kg, 1.5 mg/kg

Administration:

Oral gavage

Result:

Was efficacious in attenuating fever when administered to cats 1 or 14 hours before LPS challenge.