(2S,5R)-N-(1-methylpiperidin-4-yl)-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carboxamide | 1552306-81-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,5R)-N-(1-methylpiperidin-4-yl)-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carboxamide
• CAS: 1552306-81-6
• 化学式: C₂₀H₂₈N₄O₃
• 分子量: 372.467
• InChiKey: MZUWIVRJVSMXBX-MSOLQXFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  65.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,5R)-N-(1-methylpiperidin-4-yl)-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 在 吡啶 、 palladium 10% on activated carbon 、 氢气 、 三氧化硫吡啶 作用下， 以 甲醇 为溶剂， 生成 (2S,5R)-7-oxo-N-[1-methylpiperidin-4-yl]-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide
  参考文献：
  名称：

  Discovery of MK-7655, a β-lactamase inhibitor for combination with Primaxin®

  摘要：

  beta-Lactamase inhibitors with a bicyclic urea core and a variety of heterocyclic side chains were prepared and evaluated as potential partners for combination with imipenem to overcome class A and C beta-lactamase mediated antibiotic resistance. The piperidine analog 3 (MK-7655) inhibited both class A and C beta-lactamases in vitro. It effectively restored imipenem's activity against imipenem-resistant Pseudomonas and Klebsiella strains at clinically achievable concentrations. A combination of MK-7655 and Primaxin (R) is currently in phase II clinical trials for the treatment of Gram-negative bacterial infections. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.101
• 作为产物：
  描述：

  4-氨基-1-甲基哌啶 、 (2S,5R)-6-(苄氧基)-7-氧代-1,6-二氮杂双环[3.2.1]辛烷-2-羧酸 在 2-氯-1-甲基吡啶碘化物 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以84%的产率得到(2S,5R)-N-(1-methylpiperidin-4-yl)-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carboxamide
  参考文献：
  名称：

  Discovery of MK-7655, a β-lactamase inhibitor for combination with Primaxin®

  摘要：

  beta-Lactamase inhibitors with a bicyclic urea core and a variety of heterocyclic side chains were prepared and evaluated as potential partners for combination with imipenem to overcome class A and C beta-lactamase mediated antibiotic resistance. The piperidine analog 3 (MK-7655) inhibited both class A and C beta-lactamases in vitro. It effectively restored imipenem's activity against imipenem-resistant Pseudomonas and Klebsiella strains at clinically achievable concentrations. A combination of MK-7655 and Primaxin (R) is currently in phase II clinical trials for the treatment of Gram-negative bacterial infections. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.101

文献信息

• B-LACTAMASE INHIBITOR AND APPLICATION THEREOF
  申请人：Xuanzhu Pharma Co., Ltd.

  公开号：EP3281942A1

  公开（公告）日：2018-02-14

  The present invention relates to a compound of Formula (I)-(IV) useful as β-lactamase inhibitor, a pharmaceutically acceptable salt, ester, solvate or stereoisomer thereof, wherein R1, R2, M and ring A have definitions as those in the specification. The present invention further relates to methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and uses of these compounds. For example, the compounds of the present invention can be used as β-lactamase inhibitors, for treatment and/or prophylaxis of diseases caused by bacterial infections, solving drug-resistance problems caused by β-lactamases, especially bacterial drug-resistant diseases caused by type B metallo-β-lactamases.

  本发明涉及一种化合物，其化学式为（I）-（IV），可用作β-内酰胺酶抑制剂，其药学上可接受的盐、酯、溶剂合物或立体异构体，其中R1、R2、M和环A的定义如规范中所述。本发明还涉及制备这些化合物的方法，包括这些化合物的药物组合物，以及这些化合物的用途。例如，本发明的化合物可用作β-内酰胺酶抑制剂，用于治疗和/或预防由细菌感染引起的疾病，解决β-内酰胺酶引起的药物耐药问题，特别是由B型金属β-内酰胺酶引起的细菌耐药性疾病。
• β-lactamase inhibitors and uses thereof
  申请人：Xuanzhu Pharma Co., Ltd.

  公开号：US10167283B2

  公开（公告）日：2019-01-01

  The present invention relates to a compound of Formula (I)-(IV) useful as β-lactamase inhibitor, a pharmaceutically acceptable salt, ester, solvate or stereoisomer thereof, wherein R1, R2, M and ring A have definitions as those in the specification. The present invention further relates to methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and uses of these compounds. For example, the compounds of the present invention can be used as β-lactamase inhibitors, for treatment and/or prophylaxis of diseases caused by bacterial infections, solving drug-resistance problems caused by β-lactamases, especially bacterial drug-resistant diseases caused by type B metallo-β-lactamases.

  本发明涉及一种可用作β-内酰胺酶抑制剂的式(I)-(IV)化合物及其药学上可接受的盐、酯、溶剂或立体异构体，其中R1、R2、M和环A的定义与说明书中的定义相同。本发明进一步涉及制备这些化合物的方法、包含这些化合物的药物组合物以及这些化合物的用途。例如，本发明的化合物可用作β-内酰胺酶抑制剂，用于治疗和/或预防由细菌感染引起的疾病，解决由β-内酰胺酶引起的耐药性问题，特别是由B型金属-β-内酰胺酶引起的细菌耐药性疾病。
• [EN] Β-LACTAMASE INHIBITOR AND APPLICATION THEREOF<br/>[FR] INHIBITEUR DE SS-LACTAMASE ET SON APPLICATION<br/>[ZH] β-内酰胺酶抑制剂及其用途
  申请人：XUANZHU PHARMA CO LTD

  公开号：WO2017045510A1

  公开（公告）日：2017-03-23

  提供一类通式(Ⅰ)-（IV）所示的可用作β-内酰胺酶抑制剂的化合物、其药学上可接受的盐、其酯以及其立体异构体，其中R 1、R 2、M、环A如说明书中所定义；同时还提供这些化合物的制备方法，以及这些化合物的用途。例如，所述化合物可以用作β-内酰胺酶抑制剂，用于治疗和/或预防细菌感染性疾病，解决由β-内酰胺酶引起的细菌耐药性问题，特别是B类金属β-内酰胺酶导致的细菌耐药疾病。
• [EN] ANTIBACTERIAL COMPOSITION AND USE THEREOF<br/>[FR] COMPOSITION ANTIBACTÉRIENNE ET SON UTILISATION<br/>[ZH] 一种抗菌组合物及其用途
  申请人：XUANZHU PHARMA CO LTD

  公开号：WO2017167218A1

  公开（公告）日：2017-10-05

  本发明涉及医药技术领域，具体一种药物产品，其包含化合物（a）、或其药学上可接受的盐、酯或溶剂化合物、或其立体异构体，以及至少一种头孢类抗生素或其衍生物，其中，所述化合物（a）具有式（I）所示的结构。本发明还涉及一种预防和/或治疗受试者中由细菌引起的感染性疾病的方法，包括给受试者施用预防和/或治疗有效量的化合物（a）、或其药学上可接受的盐、酯、溶剂化合物、或其立体异构体，以及至少一种头孢类抗生素或其衍生物；优选地，所述细菌具有由β-内酰胺酶引起的耐药性。
• ß-LACTAMASE INHIBITORS AND USES THEREOF
  申请人：XUANZHU PHARMA CO., LTD.

  公开号：US20180148448A1

  公开（公告）日：2018-05-31

  The present invention relates to a compound of Formula (I)-(IV) useful as β-lactamase inhibitor, a pharmaceutically acceptable salt, ester, solvate or stereoisomer thereof, wherein R 1 , R 2 , M and ring A have definitions as those in the specification. The present invention further relates to methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and uses of these compounds. For example, the compounds of the present invention can be used as β-lactamase inhibitors, for treatment and/or prophylaxis of diseases caused by bacterial infections, solving drug-resistance problems caused by β-lactamases, especially bacterial drug-resistant diseases caused by type B metallo-β-lactamases.