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171228-49-2 分子结构
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4-{4-[4-(4-{[(3R,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-1-[(2S,3S)-2-hydroxypentan-3-yl]-4,5-dihydro-1H-1,2,4-triazol-5-one

ChemBase编号:72597
分子式:C37H42F2N8O4
平均质量:700.7773864
单一同位素质量:700.3297083
SMILES和InChIs

SMILES:
c1(ccc(cc1)N1CCN(CC1)c1ccc(cc1)OC[C@@H]1CO[C@](C1)(c1ccc(cc1F)F)Cn1ncnc1)n1c(=O)n(nc1)[C@H]([C@H](C)O)CC
Canonical SMILES:
CC[C@H](n1ncn(c1=O)c1ccc(cc1)N1CCN(CC1)c1ccc(cc1)OC[C@@H]1CO[C@@](C1)(Cn1cncn1)c1ccc(cc1F)F)[C@@H](O)C
InChI:
InChI=1S/C37H42F2N8O4/c1-3-35(26(2)48)47-36(49)46(25-42-47)31-7-5-29(6-8-31)43-14-16-44(17-15-43)30-9-11-32(12-10-30)50-20-27-19-37(51-21-27,22-45-24-40-23-41-45)33-13-4-28(38)18-34(33)39/h4-13,18,23-27,35,48H,3,14-17,19-22H2,1-2H3/t26-,27+,35-,37-/m0/s1
InChIKey:
RAGOYPUPXAKGKH-XAKZXMRKSA-N

引用这个纪录

CBID:72597 http://www.chembase.cn/molecule-72597.html

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名称和登记号

名称和登记号

名称 登记号
IUPAC标准名
4-{4-[4-(4-{[(3R,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-1-[(2S,3S)-2-hydroxypentan-3-yl]-4,5-dihydro-1H-1,2,4-triazol-5-one
IUPAC传统名
posaconazole
4-{4-[4-(4-{[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one
别名
2,5-Anhydro-1,3,4-trideoxy-2-C-(2,4-difluorophenyl)-4-[[4-[4-[4-[1-[(1S,2S)-1-ethyl-2-hydroxypropyl]-1,5-dihydro-5-oxo-4H-1,2,4-triazol-4-yl]phenyl]-1-piperazinyl]phenoxy]methyl]-1-(1H-1,2,4-triazol-1-yl)-D-threo-pentitol
Sch 56592
Noxafil
Posaconazole
CAS号
171228-49-2
PubChem SID
162037522
PubChem CID
468595

数据来源

数据来源

所有数据来源 商品来源 非商品来源
数据来源 数据ID
PubChem 468595 external link

理论计算性质

理论计算性质

JChem
可自由旋转的化学键 12  里宾斯基五规则 false 
Acid pKa 14.826501  质子受体
质子供体 LogD (pH = 5.5) 5.394681 
LogD (pH = 7.4) 5.4060388  Log P 5.406185 
摩尔折射率 200.7058 cm3 极化性 70.79972 Å3
极化表面积 111.79 Å2

分子性质

分子性质

理化性质 安全信息 产品相关信息 生物活性(PubChem)
溶解度
Chloroform expand 查看数据来源
DMSO expand 查看数据来源
Methanol (Sparingly) expand 查看数据来源
外观
White Solid expand 查看数据来源
熔点
170-172°C expand 查看数据来源
保存条件
-20°C expand 查看数据来源
-20°C Freezer expand 查看数据来源
MSDS下载
下载链接 expand 查看数据来源
成盐信息
Free Base expand 查看数据来源
质检报告
下载链接 expand 查看数据来源

详细说明

详细说明

Selleck Chemicals Selleck Chemicals TRC TRC
Selleck Chemicals -  S1257 external link
Research Area
Description Infection
Biological Activity
Description Posaconazole (Noxafil) is a sterol C14ɑ demethylase inhibitor with an IC50 of 0.25 nM.
Targets C14ɑ demethylase
IC50 0.25 nM [1]
In Vitro Posaconazole has potent trypanocidal activity. Amiodarone acts synergistically with Posaconazole. Posaconazole also affects and disrupts Ca2+ homeostasis in T. cruzi. Posaconazole blocks the biosynthesis of ergosterol, which is essential for parasite survival. Posaconazole has a clear, dose-dependent effect on proliferation of the epimastigote (extracellular) stages, with a minimal inhibitory concentration of 20 nM and an IC50 of 14 nM. Against the clinically relevant intracellular amastigote form of the parasite, Posaconazole is even more potent. Posaconazole has the minimal inhibitory concentration and IC50 values of 3 nM and 0.25 nM. [1] Posaconazole is active against isolates of Candida and Aspergillus spp. that exhibit resistance to Fluconazole, Voriconazole, and Amphotericin B and is much more active than the other triazoles against zygomycetes. [2]
In Vivo Treatment of infected animals with amiodarone alone reduces parasitemia, increased survival 60 days pi (0% for untreated controls vs 40% for amiodarone-treated animals) and, when given in combination with Posaconazole, delays the development of parasitemia. [1] Coadministration of Posaconazole and Boost Plus increases drug exposure compared to the administration of Posaconazole alone in the fasted state. Food, particularly meals high in fat content, significantly increases Posaconazole bioavailability. Systemic exposure to Posaconazole increases 4- and 2.6-fold when it is consumed with a high-fat and nonfat meal, respectively. [3] Posaconazole and Amiodarone may constitute an effective anti-T. cruzi therapy with low side effect. [4] At twice-daily doses of ≥15 mg/kg of body weight, Posaconazole prolongs the survival of the mice and reduces tissue burden. [5]
Clinical Trials Posaconazole has entered in a phase II clinical trial in the treatment of mycoses.
Features Posaconazole is the most advanced candidate for the treatment of Chagas disease.
Protocol
Cell Assay [1]
Cell Lines Epimastigote form of T. cruzi amastigotes
Concentrations 0 nM -4 nM
Incubation Time 96 hours
Methods The epimastigote form of the parasite is cultivated in liver infusion tryptose medium, supplemented with 10% new born calf serum at 28 °C with strong (120 rpm) agitation. Cultures are initiated at a cell density of 2 × 106 epimastigotes/mL, and Posaconazole is added at a cell density of 0.5?1.0 × 107 epimastigotes/mL. Cell densities are measured by using an electronic particle counter as well as by direct counting with a hemocytometer. Cell viability is followed by Trypan blue exclusion, using light microscopy. Amastigotes are cultured in Vero cells maintained in minimal essential medium supplemented with 1% fetal calf serum in a humidified atmosphere (95% air?5% CO2) at 37 °C. Cells are infected with 10 tissue culture-derived trypomastigotes per cell for 2 hours and then washed three times with phosphate-buffered saline (PBS) to remove nonadherent parasites. Fresh medium with and without Posaconazole is added, and the cells are incubated for 96 hours with a medium change at 48 hours. The percent of infected cells and the numbers of parasites per cell are determined directly using light microscopy, and a statistical analysis of the results is carried out. IC50 values are calculated by nonlinear regression, using the program GraFit. Fractional inhibitory concentrations (FIC) are calculated. Cytoplasmic free Ca2+ concentrations in control and drug-treated extracellular epimastigotes are determined by fluorimetric methods using Fura-2. Subcellular Ca2+ levels and mitochondrial membrane potentials are monitored on individual Vero cells infected with T. cruzi amastigotes by using time-scan confocal microscopy. Briefly, Vero cells heavily infected (72 hours) with T. cruzi amastigotes are plated onto 22 × 40 mm glass coverslips (0.15 mm thickness) and incubated simultaneously with 10 μM cell-permeant Rhod-2 and 10 μg/mL Rhodamine-123 for 50 minutes at 37 °C in culture medium and then washed and incubated with Ringer's solution, with or without amiodarone. Under the conditions used fluorescence of Rhod-2 comes mainly from intracellular Ca2+-rich compartments, like mitochondria, since its low affinity for Ca2+ limits its fluorescence in the Ca2+-poor cytoplasm of the Vero cells or amastigotes. Rhodamine-123 is a mitochondrion-specific cationic dye, which distributes across the inner mitochondrial membranes strictly according to their membrane potential.
Animal Study [1]
Animal Models Female NMRI?IVIC mice with acute Chagas' disease
Formulation Control
Doses 20 mg/kg/d
Administration Oral
References
[1] Benaim G, et al. J Med Chem. 2006, 49(3), 892-389.
[2] Sabatelli F, et al. Antimicrob Agents Chemother. 2006, 50(6), 2009-2015.
[3] Sansone-Parsons A, et al. Antimicrob Agents Chemother. 2006, 50(5), 1881-1883.
[4] Veiga-Santos P, et al. Int J Antimicrob Agents. 2012, 40, 61-71.
[5] Sun QN, et al. Antimicrob Agents Chemother. 2002, 46(7), 2310-2312.
Toronto Research Chemicals -  P689600 external link
Orally active triazole antifungal.

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参考文献

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