(3R)-2-(2,4-difluorophenyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)-1-(1H-1,2,4-triazol-1-yl)2-butanol | 844879-56-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3R)-2-(2,4-difluorophenyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)-1-(1H-1,2,4-triazol-1-yl)2-butanol
• 英文别名: (3R)-2-(2,4-difluorophenyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol；(3R)-2-(2,4-difluorophenyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yl)oxy-1-(1H-1,2,4-triazol-1-yl)-2-butanol；(3R)-2-(2,4-difluorophenyl)-3-(oxan-2-yloxy)-1-(1,2,4-triazol-1-yl)butan-2-ol
• CAS: 844879-56-7
• 化学式: C₁₇H₂₁F₂N₃O₃
• 分子量: 353.369
• InChiKey: JIOCAXCXNCXZBR-AXOLYNHLSA-N

物化性质

• 沸点：
  533.9±60.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  69.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3R)-2-(2,4-difluorophenyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)-1-(1H-1,2,4-triazol-1-yl)2-butanol 在 sodium methylate 、 4-甲基苯磺酸吡啶 、 potassium carbonate 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2R,3R)-2-(2,4-difluorophenyl)-3-(7-nitroindazol-1-yl)-1-(1,2,4-triazol-1-yl)butan-2-ol
  参考文献：
  名称：

  Discovery of novel indazole-linked triazoles as antifungal agents

  摘要：

  The in vitro and in vivo activities of a series of (2R, 3R)-2-(2,4-difluorophenyl)-3-(substituted indazol-1-yl)-1-(1H-1,2,4-triazol- 1-yl)butan-2-ol as potential antifungal agents are described. In particular, the analog 12j having 5-bromo substitution on the indazole ring exhibited significant antifungal activity against a variety of fungal cultures (Candida spp. and Aspergillus spp.). In addition, oral administration of 12j showed its excellent efficacy against Candida albicans in a murine infection model and the significantly improved survival rates of the infected mice. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.074
• 作为产物：
  描述：

  (2R)-1-(2,4-二氟苯基)-2-[(四氢-2H-吡喃-2-基)氧基]-1-丙酮 在 sodium hydride 作用下， 反应 6.75h， 生成 (3R)-2-(2,4-difluorophenyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)-1-(1H-1,2,4-triazol-1-yl)2-butanol
  参考文献：
  名称：

  光学活性抗真菌唑类。I.（2R，3R）-2-（2,4-二氟苯基）-3-巯基-1-（1H-1,2,4-三唑-1-基）-2-丁二醇的合成及抗真菌活性它的立体异构体。

  摘要：

  （2R，3R）-2-（2,4-二氟苯基）-3-巯基-1-（1H-1,2,4-三唑-1-基）-2-丁醇[（2R，3R）-7 ]和其立体异构体[（2S，3R）-，（2S，3S）-和（2R，3S）-7]是通过新开发的开环反应由旋光环氧乙烷6制备的，并评价其抗真菌活性。硫醇（2R，3R）-7在体外和体内均显示出极强的抗真菌活性。旋光性环氧乙烷（2R，3S）-6，一种用于合成含硫抗真菌唑5的有用中间体，是通过（R）-乳酸甲酯[（R）-8]经八步立体控制合成的。合成的关键步骤是（R）-乳酸的酰胺衍生物[（R）-12a]与2,4-二氟苯基-溴化镁（13）的Grignard反应。

  DOI：

  10.1248/cpb.41.1035

文献信息

• [EN] ANTIFUNGAL AZOLE DERIVATIVES HAVING A FLUOROVINYL MOIETY AND PROCESS FOR THE PREPARATION THEREOF<br/>[FR] DERIVES AZOLE ANTIFONGIQUES CONTENANT UN GROUPE FONCTIONNEL FLUOROVINYLE ET PROCEDE DE PREPARATION ASSOCIE
  申请人：KOREA RES INST CHEM TECH

  公开号：WO2005014583A1

  公开（公告）日：2005-02-17

  An azole derivative of formula (I) having a fluorovinyl moiety or a pharmaceutically acceptable salt thereof is superior to the conventional antifungal drugs in antifungal activity against a wide spectrum of pathogenic fungi, and has advantageously low toxicity.

  公式（I）的唑类衍生物具有氟乙烯基团或其药用可接受盐，对广谱病原真菌的抗真菌活性优于传统抗真菌药物，并具有低毒性的优势。
• A rational approach to chiral α-hydroxy aryl ketones from chiral aryl epoxides via regioselective, stereo retentive oxidative epoxide opening: Its application to the synthesis of antifungal Sch 42427/SM 9164
  作者：Dinesh Gala、Donald J. DiBenedetto

  DOI：10.1016/s0040-4039(00)74391-7

  日期：1994.11

  to hydroxy-protected chiral α-hydroxy aryl ketones with complete retention of the chiral center and good regioselectivity has been established. An application of this new reaction to the synthesis of antifungal Sch 42427/SM 9164 is also described.

  建立了一种新的，温和的方法，用于将手性芳基环氧化物直接转化为羟基保护的手性α-羟基芳基酮，同时完全保留手性中心并具有良好的区域选择性。还描述了该新反应在合成抗真菌Sch 42427 / SM 9164中的应用。
• Optically active azole derivatives, their production and use
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：EP0659751A1

  公开（公告）日：1995-06-28

  A process for preparing a compound of the formula (IV) or a salt thereof, , wherein R¹ is an optionally substituted aliphatic or aromatic hydrocarbon residue or an optionally substituted aromatic heterocyclic group, one of Y and Z is a nitrogen atom and the other is a methine group which may be optionally substituted with a lower alkyl group, Ar is a halogenated phenyl group, and (R) shows that the carbon atom marked with (R) has (R)-configuration, in a short period, by simple processes and with high yield and purity; and an azole compound of the formula (IV'), , wherein Ar' is a monofluorophenyl group, and the other symbols have the same meanings as above, or a salt thereof, which are useful for an antifungal therapeutic agent.

  一种制备式（IV）化合物或其盐的方法，其中R¹是可选取的取代脂肪族或芳香烃基残基或可选取的取代芳香杂环基团，Y和Z中的一个是氮原子，另一个是可能被低烷基取代的甲基基团，Ar是卤代苯基团，（R）表示标有（R）的碳原子具有（R）-构型，通过简单的过程，在短时间内高产量和高纯度地制备出所述化合物；以及式（IV'）的唑类化合物或其盐，其中Ar'是单氟苯基团，其他符号具有与上述相同的含义，这些化合物对于抗真菌治疗剂是有用的。
• Triazole compounds and antifungal compositions thereof
  申请人：Takeda Chemical Industries, Co., Ltd.

  公开号：US05405861A1

  公开（公告）日：1995-04-11

  The novel 2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-propanol derivertives of the formula (I): ##STR1## wherein, R.sup.0, R.sup.1 and R.sup.2 are the same or different and represent a hydrogen atom or a lower alkyl group; A represents a formula: ##STR2## wherein, X stands for a chemical bond or a formula: ##STR3## (wherein, X' stands for a chemical bond or an alkylene group having 1 to 5 carbon atoms which may contain sulfur or oxygen atom as the constituent atoms, R.sup.5 and R.sup.6 are the same or different and stand for a hydrogen atom or a lower alkyl group), R.sup.3 stands for an aromatic heterocyclic group which may be substituted, n denotes 0, 1 or 2), and R.sup.4 stands for a hydrogen atom or an alkanoyl group, or a physiologically acceptable salt thereof have antifungal activities, and they are used for preventing or treating infectious diseases caused by fungi.

  公式为(I)的2-(2,4-二氟苯基)-1-(1H-1,2,4-三唑-1-基)-2-丙醇衍生物，其中R.sup.0，R.sup.1和R.sup.2相同或不同，表示氢原子或较低的烷基基团；A表示一个公式：其中，X代表一个化学键或一个公式：其中，X'代表一个化学键或具有1至5个碳原子的烷基基团，其可能包含硫或氧原子作为构成原子，R.sup.5和R.sup.6相同或不同，代表氢原子或较低的烷基基团，R.sup.3代表一个可能被取代的芳香族杂环基团，n表示0,1或2，R.sup.4代表氢原子或脂肪酰基团，或其生理上可接受的盐具有抗真菌活性，它们用于预防或治疗由真菌引起的传染病。
• Triazole compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0421210A2

  公开（公告）日：1991-04-10

  The novel 2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-propanol derivertives have antifungal activities, and they are used for preventing or treating infectious diseases caused by fungi.

  新型 2-(2,4-二氟苯基)-1-(1H-1,2,4-三唑-1-基)-2-丙醇衍生物具有抗真菌活性，可用于预防或治疗由真菌引起的传染性疾病。