沙康唑 | 110588-57-3

• 物质功能分类: 原料药 - 人工合成抗感染类药 - 抗真菌类药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 沙康唑
• 中文别名: 沙柏康唑；4-[4-[4-[4-[[2-(2,4-二氟苯基)-2-(1H-L,2,4-三唑-1-基甲基)-1,3-二氧戊环-4-基]甲氧基]苯基]-1-哌嗪基]苯基]-2,4-二氢-2-(1-甲基丙基)-3H-1,2,4-三唑-3-酮
• 英文名称: Saperconazol
• 英文别名: 2-butan-2-yl-4-[4-[4-[4-[[(2S,4R)-2-(2,4-difluorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one
• CAS: 110588-57-3
• 化学式: C₃₅H₃₈F₂N₈O₄
• 分子量: 672.7
• InChiKey: HUADITLKOCMHSB-AVQIMAJZSA-N

物化性质

• 熔点：
  189.5°
• 沸点：
  812.5±75.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  49
• 可旋转键数：
  11
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  11

制备方法与用途

生物活性

Saperconazole（R66905）是一种广谱的抗真菌性三唑类药物，具有很强的抗曲霉菌活性。其MIC90值为0.19 mg/L。

靶点

• MIC90: 0.19 mg/L

体外研究

Saperconazole对所有黑曲霉（A. niger）菌株均表现出完全的抗真菌活性，仅有一个菌株例外。在浓度为0.1 μg/mL时，80%的菌株表现出完全抑制生长的效果；对于烟曲霉（A. fumigatus），这一比例达到85%，且这种效果持续了14天。

体内研究

感染烟曲霉（A. fumigatus）的所有对照鸽子在2至5天内死亡，显示出肺、气囊、肝、脾和肾的坏死性病灶。通过组织学检查和培养确认这些器官高度阳性。Saperconazole以2.5 mg/kg剂量时未表现出活性；然而，在5 mg/kg或10 mg/kg剂量下，则有92%或100%的鸽子存活，并且其器官培养结果均为阴性。在鸽子中未观察到与药物相关的不良反应。

化学性质

从乙腈中结晶，熔点为189.5℃，难溶于水。

用途

抗真菌药。

生产方法

化合物(I)和甘油在甲磺酸催化下回流缩合。产物经3,5-二硝基苯甲酰氯酰化后，通过硅胶柱色谱分离出顺式构型的产物。水解脱去3,5-二硝基苯甲酰基并用甲磺酰氯酰化后得到化合物(Ⅱ)。

化合物(Ⅲ)经烷基化后，再水解得化合物(Ⅳ)。

最后，在碱催化下将化合物(Ⅱ)和(Ⅳ)缩合得沙康唑。

文献信息

• Novel crystalline forms of conazoles and methods of making and using the same
  申请人：Remenar Julius

  公开号：US20050070551A1

  公开（公告）日：2005-03-31

  The invention provides novel soluble conazole crystalline forms (e.g. itraconazole, posaconazole and saperconazole) that include salts, co-crystals and related solvates useful as pharmaceuticals. The invention also provides pharmaceutical compositions comprising, and processes for making, these conazole crystalline forms. Methods of using such compositions for the treatment or prevention of systemic and local fungal, yeast, and dermatophyte infections are also provided.

  本发明提供了新型可溶性康唑类晶体形式（例如伊曲康唑、泊沙康唑和沙伯康唑），包括盐类、共晶体和相关溶剂化物，可用作药物。本发明还提供了包含这些康唑晶体形式的药物组合物和制备这些康唑晶体形式的方法。还提供了使用这些组合物治疗或预防系统性和局部真菌、酵母和皮肤菌感染的方法。
• SMALL MOLECULE INHIBITORS OF FIBROSIS
  申请人：THE SCRIPPS RESEARCH INSTITUTE

  公开号：US20160130258A1

  公开（公告）日：2016-05-12

  Described herein are compounds and compositions for the treatment of a fibrotic disease.

  本文介绍了用于治疗纤维化疾病的化合物和组合物。
• Novel conazole crystalline forms and related processes, pharmaceutical compositions and methods
  申请人：Transform Pharmaceuticals, Inc.

  公开号：US20040019211A1

  公开（公告）日：2004-01-29

  The invention provides novel soluble conazole crystalline forms (e.g. itraconazole, posaconazole and saperconazole) that include salts, co-crystals and related solvates useful as pharmaceuticals. The invention also provides pharmaceutical compositions comprising, and processes for making, these conazole crystalline forms. Methods of using such compositions for the treatment or prevention of systemic and local fungal, yeast, and dermatophyte infections are also provided.

  本发明提供了新型可溶性康唑类晶体形式（例如伊曲康唑、泊沙康唑和沙伯康唑），包括盐、共晶和相关溶剂化合物，可用作制药用途。本发明还提供了包括这些康唑类晶体形式的制药组合物和制备方法。本发明还提供了使用这种组合物治疗或预防全身性和局部真菌、酵母和皮肤菌感染的方法。
• PHARMACEUTICAL ORAL PREPARATION OF A COMPOUND HAVING AN ANTIFUNGIC ACTIVITY, AND PREPARATION METHOD
  申请人：Liconsa, Liberacion Controlada de Substancias Activas, S.A.

  公开号：EP1103252A1

  公开（公告）日：2001-05-30

  Pharmaceutical preparation comprising a compound having an antifungic activity as active principle, an inert core and a coat which includes said active principle, and is characterized in that said inert core has a particle size between 50 and 600 µm, and is also characterized in that said coat has a unique layer which is produced by nebulization, on said inert core, of a solution which comprises a compound having an antifungic activity, a hydrophilic polymer and a non ionic surfactant. The method is carried out by means of a coating which comprises a unique layer of the inert cores having a size comprised between 50 and 600 µm by nebulization of a solution comprised of the antifungic agent, the hydrophilic polymer and the non ionic surfactant at constant coating speed throughout the process; a single drying process of the coat is required with the same equipment.

  药物制剂，包括作为活性成分的具有抗真菌活性的化合物、惰性核心和包含所述活性成分的包衣，其特征在于所述惰性核心的粒径在 50 至 600 微米之间，其特征还在于所述包衣具有独特的层，该层是通过在所述惰性核心上雾化由具有抗真菌活性的化合物、亲水性聚合物和非离子表面活性剂组成的溶液而产生的。该方法是通过雾化由抗真菌剂、亲水性聚合物和非离子表面活性剂组成的溶液，在整个过程中以恒定的涂布速度进行涂布，从而在惰性芯上形成一层独特的涂层，其尺寸在 50 到 600 微米之间。
• Antifungal formulation and the methods for manufacturing and using the same
  申请人：Yung Shin Pharm. Ind. Co. Ltd.

  公开号：EP1350508A1

  公开（公告）日：2003-10-08

  The present invention provides novel pharmaceutical compositions for azole antimicrobial drugs such as itraconazole, saperconazole, ketoconazole, and fluconazole. The pharmaceutical compositions arc in the form of pellets which comprise a core and a drug emulsion layer, and optionally, a protective layer. The drug emulsion layer contains the azole antimicrobial drug, an emulsifier, a binder, and an absorbent aid. The preferred emulsifier is vitamin E polyethylene glycol succinate. The preferred binder is hydroxypropyl methylcellulose. The preferred absorbent aid is DL malic acid. The drug is dissolved in organic solvents. The preferred organic solvents are ethanol and methylene chloride. The protective layer contains polyethylene glycol (PEG) 20,000, which is coated on the drug emulsion layer.

  本发明提供了新型唑类抗菌药物（如伊曲康唑、萨哌康唑、酮康唑和氟康唑）的药物组合物。这些药物组合物呈弧形颗粒状，由核心层和药物乳液层以及保护层组成。药物乳液层包含唑类抗菌药物、乳化剂、粘合剂和吸附剂。首选的乳化剂是维生素 E 聚乙二醇琥珀酸酯。首选粘合剂是羟丙基甲基纤维素。优选的吸水剂是 DL 苹果酸。药物溶解在有机溶剂中。优选的有机溶剂是乙醇和二氯甲烷。保护层含有聚乙二醇（PEG）20000，涂在药物乳液层上。