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基本信息
艾沙康唑
愛莎康唑
艾莎康唑
艾沙康挫
伊沙康康唑
硫酸艾沙康唑
愛莎康唑雜質(zhì)41
艾沙康唑 100G
艾沙康唑中間體M9
RO 0094815
Isaconazole
Isavucozole
Isavuconazole
Isavuconazonium
NaMe:Isavuconazole
Isavuconazole(BAL-4815
2R,3R)-3-[4-(4-Cyanophenyl)thiazol-2-yl]-2-(2,5- difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol
4-(2-((2R,3R)-3-(2,5-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan-2-yl)thiazol-4-yl)benzonitrile
物理化學(xué)性質(zhì)
常見問題列表
艾沙康唑硫酸鹽進(jìn)入體內(nèi)后被血漿酯酶迅速轉(zhuǎn)化為活性代謝物艾沙康唑。與其他的唑類抗真菌藥相似,艾沙康唑通過抑制麥角甾醇生物合成從而破壞真菌細(xì)胞膜的形成。艾沙康唑與真菌CYP51 基因編碼的細(xì)胞色素P450 羊毛甾醇14-α-去甲基酶結(jié)合,抑制14-α-去甲基酶的活性,阻礙麥角甾醇合成,而累積的毒性甲基化甾醇影響真菌細(xì)胞膜的結(jié)構(gòu)穩(wěn)定性和完整性,并且改變其功能,最終導(dǎo)致真菌死亡。艾沙康唑結(jié)構(gòu)式分子中的側(cè)鏈與真菌CYP51 蛋白有較高的親合力,促使其具有較廣的抗真菌譜,并且包括對(duì)其他唑類抗真菌藥耐受的真菌。
一種艾沙康唑的制備方法,它包括以:下步驟:
(a)向反應(yīng)釜中依次加入二氟苯基乙酰氯、三氮唑、CuI、碳酸鉀和N,N-二甲基甲酰胺,在80~100℃攪拌反應(yīng)后提純得第一產(chǎn)物
(b)向反應(yīng)容器中加入丙腈、催化劑、第二有機(jī)溶劑,降溫至-20~-5℃,滴加含有第一產(chǎn)物的N,N-二甲基乙酰胺,反應(yīng)提純得第二產(chǎn)物所述催化劑為C-9伯胺金雞納堿和銅色樹堿組成的混合物;
(c)將第二產(chǎn)物加入另一反應(yīng)容器中,加入二硫代磷酸二乙酯、水和異丙醇混合溶劑,加熱至80~90℃,攪拌反應(yīng)后提純得第三產(chǎn)物
(d)將第三產(chǎn)物與2-溴-4’-氰基苯乙酮、95乙醇混合后,在60~70℃攪拌反應(yīng)后提 純即可。優(yōu)化地,所述催化劑為C-9伯胺金雞納堿和銅色樹堿按摩爾比為1:1組成的混合物
Isavuconazole (BAL-4815) shows good activity against all Candida spp., with active MIC 50 of 0.004 mg/L. The MIC 50 s/MIC 90 s range from 0.002/0.004 mg/L for C. albicans to 0.25/0.5 mg/L for C. glabrata . Isavuconazole has potent in vitro activity against most common Aspergillus species, Purpureocillium lilacinum , and Scedosporium apiospermum . Isavuconazole shows potent activity against molds, yeasts, and dimorphic fungi. Rhizopus isolates have MIC values to isavuconazole as low as 0.12 μg/mL with others as high as 32 μg/mL. In the study of pharmacokinetics and pharmacodynamics of isavuconazole against the GFP transformant, F/11628, NIH 4215, and F/16216, the modal MICs of isavuconazole are 1, 8, 1, 4 mg/L, respectively.