2-[4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-ylsulfonyl]acetonitrile | 1621914-72-4

• 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: 2-[4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-ylsulfonyl]acetonitrile
• 英文别名: 2-[4-[4-[[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]sulfonylacetonitrile
• CAS: 1621914-72-4
• 化学式: C₂₆H₂₇Cl₂N₅O₅S
• 分子量: 592.503
• InChiKey: VQVCXLJVBQAPQH-ZEQKJWHPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  118
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  氰基甲磺酰氯 、 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 24.0h， 以75%的产率得到2-[4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-ylsulfonyl]acetonitrile
  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

• [EN] NOVEL FUNCTIONALIZED 4-(PHENOXYMETHYL(-1,3-DIOXOLANE ANALOGS EXHIBITING CYTOCHROME P450 INHIBITION AND THEIR METHOD OF USE<br/>[FR] NOUVEAUX ANALOGUES 4-(PHÉNOXYMÉTHYL)-1,3-DIOXOLANE FONCTIONNALISÉS PRÉSENTANT UNE INHIBITION DU CYTOCHROME P450 ET LEUR PROCÉDÉ D'UTILISATION
  申请人：CORTENDO AB PUBL

  公开号：WO2014122530A1

  公开（公告）日：2014-08-14

  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。
• 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。
• Design, synthesis, and evaluation of (2 S ,4 R )-Ketoconazole sulfonamide analogs as potential treatments for Metabolic Syndrome
  作者：Benjamin E. Blass、Pravin Iyer、Magid Abou-Gharbia、Wayne E. Childers、John C. Gordon、Mercy Ramanjulu、George Morton、Premkumar Arumugam、Joshodeep Boruwa、John Ellingboe、Sayan Mitra、Rajashekar Reddy Nimmareddy、Shalini Paliwal、Jamallamudi Rajasekhar、Savithiri Shivakumar、Pratima Srivastava、Raghuram S. Tangirala、Konda Venkataramanaiah、Mahesh Yanamandra

  DOI：10.1016/j.bmcl.2016.10.016

  日期：2016.12

  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.