[(1R,5S,6r)-3-benzyl-3-azabicyclo[3.1.0]hex-6-yl]methyl methanesulfonate | 1366664-25-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: [(1R,5S,6r)-3-benzyl-3-azabicyclo[3.1.0]hex-6-yl]methyl methanesulfonate
• 英文别名: (exo-3-benzyl-3-azabicyclo[3.1.0]hexan-6-yl)methyl methanesulfonate；(1α,5α,6α)-6-(methylsulphonyloxy)methyl-3-benzyl-3-aza-bicyclo[3.1.0]hexane；(1α,5α,6α)-3-benzyl-6-methanesulphonyloxymethyl-3-aza-bicyclo[3.1.0]hexane
• CAS: 1366664-25-6；848143-95-3
• 化学式: C₁₄H₁₉NO₃S
• 分子量: 281.376
• InChiKey: PQQZJPFOUPZLBS-WDNDVIMCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.34
• 重原子数：
  19.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  46.61
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  [(1R,5S,6r)-3-benzyl-3-azabicyclo[3.1.0]hex-6-yl]methyl methanesulfonate 在 硫酸 、 10% palladium hydroxide on charcoal 、 氢气 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 80.0 ℃ 、344.75 kPa 条件下， 反应 48.0h， 生成 (1α,5α,6α)-(3-aza-bicyclo[3.1.0]hex-6-yl)-acetic acid ethyl ester
  参考文献：
  名称：

  Discovery of PF-06835919: A Potent Inhibitor of Ketohexokinase (KHK) for the Treatment of Metabolic Disorders Driven by the Overconsumption of Fructose

  摘要：

  Increased fructose consumption and its subsequent metabolism have been implicated in metabolic disorders such as nonalcoholic fatty liver disease and steatohepatitis (NAFLD/NASH) and insulin resistance. Ketohexokinase (KHK) converts fructose to fructose-1-phosphate (F1P) in the first step of the metabolic cascade. Herein we report the discovery of a first-in-class KHK inhibitor, PF-06835919 (8), currently in phase 2 clinical trials. The discovery of 8 was built upon our originally reported, fragment-derived lead 1 and the recognition of an alternative, rotated binding mode upon changing the ribose-pocket binding moiety from a pyrrolidinyl to an azetidinyl ring system. This new binding mode enabled efficient exploration of the vector directed at the Arg-108 residue, leading to the identification of highly potent 3-azabicyclo[3.1.0]hexane acetic acid-based KHK inhibitors by combined use of parallel medicinal chemistry and structure-based drug design.

  DOI：

  10.1021/acs.jmedchem.0c00944
• 作为产物：
  描述：

  甲基磺酰氯 、 exo-N-benzyl-3-azabicyclo[3.1.0]hexane-6-methanol 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以74%的产率得到[(1R,5S,6r)-3-benzyl-3-azabicyclo[3.1.0]hex-6-yl]methyl methanesulfonate
  参考文献：
  名称：

  Xanthine Derivatives a Useful as Muscarinic Receptor Antagonists

  摘要：

  这项发明通常涉及黄嘌呤衍生物作为肌氨酸受体拮抗剂，这些衍生物在其他用途中可用于治疗通过肌氨酸受体介导的呼吸系统、泌尿系统和消化系统的各种疾病。该发明还涉及所述化合物的制备方法、含有所述化合物的药物组合物，以及治疗通过肌氨酸受体介导的疾病的方法。

  公开号：

  US20080319002A1

文献信息

• [EN] XANTHINE DERIVATIVES USEFUL AS MUSCARINIC RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE XANTHINE UTILISES EN TANT QU'ANTAGONISTES DU RECEPTEUR MUSCARINIQUE
  申请人：RANBAXY LAB LTD

  公开号：WO2006005980A1

  公开（公告）日：2006-01-19

  This present invention generally relates to xanthine derivatives as muscarinic receptor antagonists which are useful, among other uses, for the treatment of various diseases of the respiratory, urinary and gastrointestinal systems mediated through muscarinic receptors. The invention also relates to the process for the preparation of disclosed compounds, pharmaceutical compositions containing the disclosed compounds, and the methods for treating diseases mediated through muscarinic receptors.

  这项发明通常涉及黄嘌呤衍生物作为肌氨酸受体拮抗剂，这些衍生物在其他用途中可用于治疗通过肌氨酸受体介导的呼吸系统、泌尿系统和消化系统的各种疾病。该发明还涉及所述化合物的制备方法、含有所述化合物的药物组合物，以及治疗通过肌氨酸受体介导的疾病的方法。
• Xanthine Derivatives a Useful as Muscarinic Receptor Antagonists
  申请人：Mehta Anita

  公开号：US20080319002A1

  公开（公告）日：2008-12-25

  This present invention generally relates to xanthine derivatives as muscarinic receptor antagonists which are useful, among other uses, for the treatment of various diseases of the respiratory, urinary and gastrointestinal systems mediated through muscarinic receptors. The invention also relates to the process for the preparation of disclosed compounds, pharmaceutical compositions containing the disclosed compounds, and the methods for treating diseases mediated through muscarinic receptors.

  这项发明通常涉及黄嘌呤衍生物作为肌氨酸受体拮抗剂，这些衍生物在其他用途中可用于治疗通过肌氨酸受体介导的呼吸系统、泌尿系统和消化系统的各种疾病。该发明还涉及所述化合物的制备方法、含有所述化合物的药物组合物，以及治疗通过肌氨酸受体介导的疾病的方法。
• SUBSTITUTED 3-AZABICYCLO[3.1.0]HEXANES AS KETOHEXOKINASE INHIBITORS
  申请人：Pfizer Inc.

  公开号：US20170183328A1

  公开（公告）日：2017-06-29

  Provided herein are substituted 3-azabicyclo[3.1.0]hexanes as ketohexokinase inhibitors, processes to make said compounds, and methods comprising administering said compounds to a mammal in need thereof.

  本文提供了替代3-氮杂双环[3.1.0]己烷作为酮己糖激酶抑制剂，制备该类化合物的方法，以及包括向需要的哺乳动物施用该类化合物的方法。
• [EN] PROCESS FOR THE PREPARATION OF (1alpha, 5alpha, 6alpha)-6-AMINOMETHYL-3-BENZYL-3-AZBICYCLO[3.1.0]HEXANE<br/>[FR] PROCEDE DE PREPARATION DE (1 DOLLAR G(A), 5 DOLLAR G(A), 6 DOLLAR G(A))-6-AMINOMETHYL-3-BENZYL-3-AZABICYCLO[3.1.0]HEXANE
  申请人：RANBAXY LAB LTD

  公开号：WO2005026122A1

  公开（公告）日：2005-03-24

  The present invention relates to a new and industrially advantageous process for the preparation of (1α , 5α , 6α )-6-aminomethyl-3-benzyl-3-azabicyclo[3.1.0]hexane, a key intermediate for the synthesis of azabicyclo quinolone derivatives as antimicrobials and for the synthesis of various azabicyclo[3.1.0]hexane derivatives.

  本发明涉及一种新的、在工业上具有优势的制备(1α, 5α, 6α)-6-氨甲基-3-苄基-3-氮杂双环[3.1.0]己烷的过程，该过程是合成氮杂双环喹诺酮衍生物作为抗微生物药物和合成各种氮杂双环[3.1.0]己烷衍生物的关键中间体。
• [EN] COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH STING ACTIVITY<br/>[FR] COMPOSÉS ET COMPOSITIONS POUR TRAITER DES ÉTATS PATHOLOGIQUES ASSOCIÉS À UNE ACTIVITÉ DE STING
  申请人：IFM DUE INC

  公开号：WO2022015977A1

  公开（公告）日：2022-01-20

  This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that inhibit (e.g., antagonize) Stimulator of Interferon Genes (STING). Said chemical entities are useful, e.g., for treating a condition, disease or disorder in which increased (e.g., excessive) STING activation (e.g., STING signaling) contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also features compositions containing the same as well as methods of using and making the same.

  本公开涉及化学实体（例如，化合物或药物可接受的盐，水合物，共晶体或化合物的药物组合），其抑制（例如，对抗）干扰素基因刺激剂（STING）。这些化学实体是有用的，例如，用于治疗在该主题（例如，人类）中增加（例如，过度）STING激活（例如，STING信号传导）对病理学和/或症状和/或病情进展有贡献的状况，疾病或障碍（例如，癌症）。本公开还涉及包含相同的组合物以及使用和制造相同的方法。