1-[2-[(2,6-二氯苯基)甲氧基]-2-(2,4-二氯苯基)乙基]-1H-咪唑单硝酸盐 | 24168-96-5

• 物质功能分类: 原料药 - 抗生素类药物 - 其它抗生素类药
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-[2-[(2,6-二氯苯基)甲氧基]-2-(2,4-二氯苯基)乙基]-1H-咪唑单硝酸盐
• 中文别名: 硝酸邻氯益康唑；硝酸异康唑；1-[2-(2,4-二氯苯基)-2-[(2,6-二氯苯基)甲氧基]乙基]-1H-咪唑单硝酸盐
• 英文名称: Fazol
• 英文别名: 1-[2-(2,6-dichlorobenzyloxy)-(2,6-dichlorophenyl)ethyl]-1H-imidazole nitrate；isoconazole nitrate；sulconazole nitrate；Travogen；1-[2,4-dichloro-β-(2,6-dichlorobenzyloxy)-phenethyl]-imidazole nitrate；1-[2-(2,4-dichlorophenyl)-2-[(2,6-dichlorophenyl)methoxy]ethyl]imidazole;nitric acid
• CAS: 24168-96-5；40036-10-0
• 化学式: C₁₈H₁₄Cl₄N₂O*HNO₃
• 分子量: 479.147
• InChiKey: NNGQLSIGRSTLLU-UHFFFAOYSA-N

物化性质

• 熔点：
  178-182°C
• 溶解度：
  极微溶于水，溶于甲醇，微溶于乙醇（96%）。

计算性质

• 辛醇/水分配系数(LogP)：
  6.11
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  93.1
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2933290090
• WGK Germany：
  3
• 包装等级：
  III
• 危险类别：
  5.1
• 危险性防范说明：
  P220,P210,P264,P280,P370+P378,P337+P313
• 危险品运输编号：
  1479
• 危险性描述：
  H315,H319,H272

制备方法与用途

概述

硝酸异康唑是一种具有广泛抗真菌作用的咪唑类药物，对白色念珠菌、表皮癣菌以及某些革兰阳性菌均有抑制效果。1979年，该药物在法国上市，并因其显著疗效和低毒副作用而拥有广阔的市场前景。

生物活性

Isoconazole nitrate 是一种唑类抗真菌药。

体外研究

硝酸异康唑（ISN）不仅能够通过抑制麦角固醇合成来作用于真菌膜，还表现出其他多种独立的效应。在体外暴露10分钟后，硝酸异康唑迅速减少细胞内的三磷酸腺苷 (ATP)。当浓度为1 μg/mL 和 10 μg/mL 时，ISN 在体外通过影响细胞膜的合成和组织诱导了细胞分裂受阻。而当其浓度提高到50 μg/mL 和 100 μg/mL 时，则会导致真菌细胞发生坏死和死亡。

用途

硝酸异康唑是一种广谱抗真菌药。

反应信息

• 作为反应物：
  描述：

  copper(II) acetate monohydrate 、 1-[2-[(2,6-二氯苯基)甲氧基]-2-(2,4-二氯苯基)乙基]-1H-咪唑单硝酸盐 以 甲醇 为溶剂， 反应 0.67h， 以58%的产率得到[Cu(acetate)₂(isoconazole)₂]*2H₂O
  参考文献：
  名称：

  New copper(II) complexes with isoconazole: Synthesis, structures and biological properties

  摘要：

  There is an increasing demand for novel metal-based complexes with biologically relevant molecules in technology and medicine. Three new Cu(II) coordination compounds with antifungal agent isoconazole (L), namely mononuclear complexes [CuCl2(L)(2)] (1), and [Cu(O2CMe)(2)(L)(2)]center dot 2H(2)O (2) and coordination polymer [Cu(pht)(L)(2)](n) (3) (where H(2)pht - o-phthalic acid) were synthesized and characterized by IR spectroscopy, thermogravimetric analysis and X-ray crystallography. X-ray analysis showed that in all complexes, the isoconazole is coordinated to Cu(II) centres by a N atom of the imidazole fragment. In complex I, the square-planar environment of Cu(II) atoms is completed by two N atoms of isoconazole and two chloride ligands, whereas the Cu(II) atoms are coordinated by two N atoms from two isoconazole ligands and two O atoms from the different carboxylate residues: acetate in 2 and phthalate in 3. The formation of an infinite chain through the bridging phthalate ligand is observed in 3. The biosynthetic ability of micromycetes Aspergillus niger CNMN FD 10 in the presence of the prepared complexes 1-3 as well as the antifungal drug isoconazole were studied. Complexes 2 and 3 accelerate the biosynthesis of enzymes (beta-glucosidase, xylanase and endoglucanase) by this fungus. Moreover, a simplified and improved method for the preparation of isoconazole nitrate was developed. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.poly.2012.10.040
• 作为产物：
  描述：

  2-溴-2',4'-二氯苯乙酮 在 sodium tetrahydroborate 、 硝酸 、 sodium hydride 作用下， 以 1,4-二氧六环 、 异丙醇 、 丙酮 、 乙腈 、 mineral oil 为溶剂， 反应 15.0h， 生成 1-[2-[(2,6-二氯苯基)甲氧基]-2-(2,4-二氯苯基)乙基]-1H-咪唑单硝酸盐
  参考文献：
  名称：

  New copper(II) complexes with isoconazole: Synthesis, structures and biological properties

  摘要：

  There is an increasing demand for novel metal-based complexes with biologically relevant molecules in technology and medicine. Three new Cu(II) coordination compounds with antifungal agent isoconazole (L), namely mononuclear complexes [CuCl2(L)(2)] (1), and [Cu(O2CMe)(2)(L)(2)]center dot 2H(2)O (2) and coordination polymer [Cu(pht)(L)(2)](n) (3) (where H(2)pht - o-phthalic acid) were synthesized and characterized by IR spectroscopy, thermogravimetric analysis and X-ray crystallography. X-ray analysis showed that in all complexes, the isoconazole is coordinated to Cu(II) centres by a N atom of the imidazole fragment. In complex I, the square-planar environment of Cu(II) atoms is completed by two N atoms of isoconazole and two chloride ligands, whereas the Cu(II) atoms are coordinated by two N atoms from two isoconazole ligands and two O atoms from the different carboxylate residues: acetate in 2 and phthalate in 3. The formation of an infinite chain through the bridging phthalate ligand is observed in 3. The biosynthetic ability of micromycetes Aspergillus niger CNMN FD 10 in the presence of the prepared complexes 1-3 as well as the antifungal drug isoconazole were studied. Complexes 2 and 3 accelerate the biosynthesis of enzymes (beta-glucosidase, xylanase and endoglucanase) by this fungus. Moreover, a simplified and improved method for the preparation of isoconazole nitrate was developed. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.poly.2012.10.040

文献信息

• [EN] PHARMACEUTICAL COMPOSITIONS OF POLYANIONIC AND NON-IONIC CYCLODEXTRIN-BASED DENDRIMERS AND USES THEREOF<br/>[FR] COMPOSITIONS PHARMACEUTIQUES DE DENDRIMÈRES À BASE DE CYCLODEXTRINE POLYANIONIQUE ET NON-IONIQUE ET UTILISATIONS ASSOCIÉES
  申请人：LING CHANG-CHUN

  公开号：WO2016161501A1

  公开（公告）日：2016-10-13

  The present application provides pharmaceutical compositions comprising polyanionic and polynon-ionic cyclodextrin-based dendrimers. The compositions can be used as excipients, or to bind to compounds such as in the use as a rescue medicine to remove undesired drugs and metabolites from a subject. Methods of use in treating a subject are also provided.

  当前申请提供了包含多阴离子和多非离子环糊精基树枝状聚合物的药物组合物。这些组合物可以用作辅料，或者用于结合化合物，例如用作救援药物以从主体中去除不需要的药物和代谢物。还提供了用于治疗主体的方法。
• GAMMA-AAPEPTIDES WITH POTENT AND BROAD-SPECTRUM ANTIMICROBIAL ACTIVITY
  申请人：Cai Jianfeng

  公开号：US20150274782A1

  公开（公告）日：2015-10-01

  The present invention is directed to a novel class of antimicrobial agents called γ-AApeptides. The current invention provides various categories of γ-AApeptides, for example, linear γ-AApeptides, cyclic γ-AApeptides, and lipidated γ-AApeptides. γ-AApeptides of the current invention are designed to exert antimicrobial activity while being stable and non-toxic. γ-AApeptides also do not appear to lead to the development of microbial resistance in treated microorganisms. Thus, the disclosed γ-AApeptides can be used for the treatment of various medical conditions associated with pathogenic microorganisms.

  本发明涉及一种新型类别的抗微生物药物，称为γ-AA肽。当前发明提供了各种类别的γ-AA肽，例如线性γ-AA肽、环状γ-AA肽和脂质化γ-AA肽。本发明的γ-AA肽被设计为具有抗微生物活性，同时稳定且无毒。γ-AA肽似乎也不会导致被治疗微生物体内微生物产生抗药性。因此，所披露的γ-AA肽可用于治疗与病原微生物相关的各种医疗状况。
• External preparation for skin diseases containing nitroimidazole
  申请人：——

  公开号：US20030092754A1

  公开（公告）日：2003-05-15

  An external preparation for skin disease which comprises a nitroimidazole derivative represented by the following formula (I): 1 wherein R 1 , R 3 and R 4 may be the same or different and represent a hydrogen atom, a nitro group, a lower alkyl group, a substituted lower alkyl group, a lower alkenyl group, or a substituted lower alkenyl group; and R 2 represents a hydrogen atom, a lower alkyl group, a substituted lower alkyl group and a lower alkenyl group or a substituted lower alkenyl group, provided that any one of R 1 , R 3 and R 4 is a nitro group.

  一种外用制剂，用于皮肤疾病，包括以下式(I)所代表的硝基咪唑衍生物：1其中R1、R3和R4可以相同也可以不同，并表示氢原子、硝基、低烷基、取代的低烷基、低烯基或取代的低烯基；R2表示氢原子、低烷基、取代的低烷基和低烯基或取代的低烯基，只要R1、R3和R4中的任何一个是硝基。
• MANUFACTURING METHOD AND APPARATUS OF ULTRAFINE PARTICLES HAVING UNIFORM PARTICLE SIZE DISTRIBUTION
  申请人：Hwang Sung Joo

  公开号：US20110200678A1

  公开（公告）日：2011-08-18

  The present invention relates to a novel technology for forming fine particles with a size of 0.02˜3 microns from a solid that can be dissolved in a liquid solvent and is not decomposed by heat. The particle preparation technology according to the present invention may be applicable to the fields of food, cosmetics, biopolymer, polymer compositions, and pharmaceuticals.

  本发明涉及一种新型技术，用于从可溶于液体溶剂且不会被热分解的固体中形成粒径为0.02〜3微米的细小颗粒。本发明的颗粒制备技术可适用于食品、化妆品、生物聚合物、聚合物组合物和制药等领域。
• Medical composition for external application
  申请人：Kao Corporation

  公开号：EP0179277A1

  公开（公告）日：1986-04-30

  57 A medical composition for external application comprises a dialkyl phosphate represented by the formula: wherein R, and R2 independently represent a hydrocarbon group having from 6 to 24 carbon atoms, R3 and R. independently represent hydrocarbon group having from 2 to 6 carbon atoms, m and n indepedently represent a value of from 0 to 20, and x represents a hydrogen atom or a salt of an alkali metal and the like. In the presence of the dialkyl phosphate, percutaneous intake of medically active ingredients is highly enhanced. Examples of the medically active ingredients directed to in the invention include antiinflammatory agents such as ethyl aminobenzoate; adrenocortical hormones such as hydrocortisone; etc. The inventive composition is highly safe without giving any stimulation to the skin.

  57 用于外用的医疗组合物包括由式表示的磷酸二烷基酯：其中 R 和 R2 独立地代表具有 6 至 24 个碳原子的烃基，R3 和 R.独立地代表具有 2 至 6 个碳原子的烃基，m 和 n 独立地代表 0 至 20 的值，x 代表氢原子或碱金属盐等。 在磷酸二烷基酯存在的情况下，经皮摄入医疗活性成分的效果非常好。 本发明所涉及的医疗活性成分包括抗炎剂（如氨基苯甲酸乙酯）、肾上腺皮质激素（如氢化可的松）等，本发明组合物非常安全，不会对皮肤造成任何刺激。