1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine | 67914-61-8

• 物质功能分类: 有机原料 - 酮类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine
• 英文别名: 1-[4-[[(2RS,4SR)-2-(2,4-Dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-piperazine；1-[4-[[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine
• CAS: 67914-61-8
• 化学式: C₂₄H₂₆Cl₂N₄O₃
• 分子量: 489.401
• InChiKey: LOUXSEJZCPKWAX-ZJSXRUAMSA-N

物化性质

• 熔点：
  173℃
• 沸点：
  699.7±55.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)
• 溶解度：
  氯仿（微溶）、DMSO（微溶）、甲醇（微溶，超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  60.8
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  储存条件：2-8℃，避光，干燥，密封。

制备方法与用途

Deacylketoconazole is a derivative of ketoconazole, which is an antifungal medication primarily used to treat fungal infections.

反应信息

• 作为反应物：
  描述：

  氯乙基异氰酸酯 、 1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 42.0h， 生成 1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-(4,5-dihydro-1,3-oxazol-2-yl)piperazine
  参考文献：
  名称：

  [EN] NOVEL FUNCTIONALIZED 4-(PHENOXYMETHYL(-1,3-DIOXOLANE ANALOGS EXHIBITING CYTOCHROME P450 INHIBITION AND THEIR METHOD OF USE
  [FR] NOUVEAUX ANALOGUES 4-(PHÉNOXYMÉTHYL)-1,3-DIOXOLANE FONCTIONNALISÉS PRÉSENTANT UNE INHIBITION DU CYTOCHROME P450 ET LEUR PROCÉDÉ D'UTILISATION

  摘要：

  本发明实施例涉及4-(苯氧甲基)-1,3-二噁烷类似物及其药物组合物，在治疗与皮质醇过度产生相关的疾病方面具有疾病修饰作用，包括代谢综合征以及任何涉及皮质醇过度产生的疾病。

  公开号：

  WO2014122530A1
• 作为产物：
  描述：

  ketoconazole 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 18.0h， 生成 1-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine
  参考文献：
  名称：

  Design, synthesis, and evaluation of (2 S ,4 R )-Ketoconazole sulfonamide analogs as potential treatments for Metabolic Syndrome

  摘要：

  Metabolic Syndrome, also referred to as 'Syndrome X' or 'Insulin Resistance Syndrome,' remains a major, unmet medical need despite over 30 years of intense effort. Recent research suggests that there may be a causal link between this condition and abnormal glucocorticoid processing. Specifically, dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis leads to increased systemic cortisol concentrations. Cushing' syndrome, a disorder that is also typified by a marked elevation in levels of cortisol, produces clinical symptomology that is similar to those observed in MetS, and they can be alleviated by decreasing circulating cortisol concentrations. As a result, it has been suggested that decreasing systemic cortisol concentration might have a positive impact on the progression of MetS. This could be accomplished through inhibition of enzymes in the cortisol synthetic pathway, 11 beta-hydroxylase (Cyp11B1), 17 alpha-hydroxylase-C17,20-lyase (Cyp17), and 21-hydroxylase (Cyp21). We have identified a series of novel sulfonamide analogs of (2S, 4R)-Ketoconazole that are potent inhibitors of these enzymes. In addition, selected members of this class of compounds have pharmacokinetic properties consistent with orally delivered drugs, making them well suited to further investigation as potential therapies for MetS. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.10.016

文献信息

• NOVEL FUNCTIONALIZED 4-(PHENOXYMETHYL(-1,3-DIOXOLANE ANALOGS EXHIBITING CYTOCHROME P450 INHIBITION AND THEIR METHOD OF USE
  申请人：CORTENDO AB (PUBL)

  公开号：US20150353530A1

  公开（公告）日：2015-12-10

  Embodiments of the present invention relate to 4-(phenoxymethyl)-1,3-dioxolane analogs and pharmaceutical compositions thereof having a disease-modifying action in the treatment of diseases associated with the overproduction of cortisol that include metabolic syndrome, and any involving the overproduction of cortisol.

  本发明实施例涉及4-(苯氧甲基)-1,3-二氧杂环己烷类似物及其制药组合物，具有治疗与皮质醇过度产生相关的疾病的疾病改善作用，包括代谢综合征和任何涉及皮质醇过度产生的疾病。
• Derivatives of (4-(piperazin-1-yl-phenyloxymethyl)-1.3-dioxolan-2-ylmethyl)-1H-imidazoles and -1H-1.2.4-triazoles, their preparation and use as fungicides and bactericides
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP0006722A1

  公开（公告）日：1980-01-09

  Compounds having the formula: and the pharmaceutically acceptable acid addition salts and stersochemically isomeric forms thersof, wherein: Q is a member selected from the group consisting of N and CH; Ar is a member selected from the group consisting of thienyl, halothienyl, phenyl and substituted phenyl; and Y is a member selected from the group consisting of a) SO2R1, wherein R' is trifluormethyl and aryl and b) substituted alkyl and alkenyl. The compounds are useful as antifungal and antibacterial agents.

  具有以下式子的化合物：及其药学上可接受的酸加成盐和异构体，其中：Q 是选自 N 和 CH 组成的组的成员；Ar 是选自噻吩基、卤代噻吩基、苯基和取代苯基组成的组的成员；Y 是选自 a) SO2R1（其中 R' 为三氟甲基和芳基）和 b) 取代烷基和烯基组成的组的成员。 这些化合物可用作抗真菌剂和抗菌剂。
• Heterocyclic derivatives of (4-(piperazin-1-yl-phenyloxymethyl)-1.3.-dioxolan-2-ylmethyl)-1H-imidazoles and -1H-1.2.4-triazoles, their preparation and use as fungicides and bactericides
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP0007696A1

  公开（公告）日：1980-02-06

  1 H-Imidazole and 1H-1,2,4-triazole derivatives which may structurally be represented by the formula: and the pharmaceutically acceptable acid addition salts and stereochemically isomeric forms thereof, wherein: Q is a member selected from the group consisting of CH and N; Ar is a member selected from the group consisting of phenyl, thienyl, halothienyl and substituted phenyl; and Y is an optionally substituted mono- or binuclear nitrogen-containing heteroaromatic radical. The compounds are useful as antifungal and antibacterial agents.

  1H-咪唑和 1H-1,2,4-三唑衍生物，其结构可由式表示： 及其药学上可接受的酸加成盐和立体化学异构体形式，其中 Q 是选自 CH 和 N 组成的组的成员； Ar 是选自苯基、噻吩基、卤代噻吩基和取代苯基的成员；以及 Y 是任选取代的单核或双核含氮杂芳基。这些化合物可用作抗真菌剂和抗菌剂。
• 2-Azolylmethyl-2-aryl-1,3-dioxolane und deren Salze, Verfahren zu ihrer Herstellung, sie enthaltende Mittel und ihre Verwendung
  申请人：HOECHST AKTIENGESELLSCHAFT

  公开号：EP0237963A2

  公开（公告）日：1987-09-23

  Beschrieben werden Verbindungen I mit A gleich CH oder N; Ar gleich Naphtyl, Thienyl, Phenyl; R1 gleich Alkyl, F, Cl; g gleich null,1,2; Y gleich verschiedene heterocyclische Basen sowie deren Säureadditionssalze. Beschrieben werden mehrere Herstellungsverfahren. Verbindungen llla mit R1, g und Y wie zu Formel I angegeben dienen als Zwischenprodukte zu deren Herstellung. Auch für die Herstellung von IIIa sind Verfahren angegeben. stellen wertvolle Antimykotika dar.

  其中 A 是 CH 或 N；Ar 是萘基、噻吩基、苯基；R1 是烷基、F、Cl；g 是零、1、2；Y 是各种杂环碱及其酸加成盐。 描述了几种生产工艺。 式 I 中含有 R1、g 和 Y 的化合物 llla 可作为其生产的中间体。 还给出了 IIIa 的生产工艺。
• US4144346A
  申请人：——

  公开号：US4144346A

  公开（公告）日：1979-03-13