benzyl (S)-1-[(1S,2R,4R)-4-amino-2-propylcyclohexyl]-2-oxopyrrolidin-3-ylcarbamate | 848001-48-9

• 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: benzyl (S)-1-[(1S,2R,4R)-4-amino-2-propylcyclohexyl]-2-oxopyrrolidin-3-ylcarbamate
• 英文别名: benzyl N-[(3S)-1-[(1S,2R,4R)-4-amino-2-propylcyclohexyl]-2-oxopyrrolidin-3-yl]carbamate
• CAS: 848001-48-9
• 化学式: C₂₁H₃₁N₃O₃
• 分子量: 373.495
• InChiKey: KBOBWSJTCCCWJY-YRXWBPOGSA-N

物化性质

• 沸点：
  569.5±50.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  84.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl (S)-1-[(1S,2R,4R)-4-amino-2-propylcyclohexyl]-2-oxopyrrolidin-3-ylcarbamate 在 sodium cyanoborohydride 作用下， 以 甲醇 、 水 为溶剂， 反应 19.17h， 生成 benzyl (S)-1-[(1S,2R,4R)-4-(isopropyl(methyl)amino)-2-propylcyclohexyl]-2-oxopyrrolidin-3-ylcarbamate
  参考文献：
  名称：

  Discovery of a Potent and Orally Bioavailable Dual Antagonist of CC Chemokine Receptors 2 and 5

  摘要：

  We describe the hybridization of our previously reported acyclic and cyclic CC chemokine receptor 2 (CCR2) antagonists to lead to a new series of dual antagonists of CCR2 and CCRS. Installation of a gamma-lactam as the spacer group and a quinazoline as a benzamide mimetic improved oral bioavailability markedly. These efforts led to the identification of 13d, a potent and orally bioavailable dual antagonist suitable for use in both murine and monkey models of inflammation.

  DOI：

  10.1021/ml500505q
• 作为产物：
  描述：

  (1R,3S,4S)-(4-benzyloxycarbonylamino-3-propenylcyclohexyl)carbamic acid tert-butyl ester 在 5%-palladium/activated carbon 、 BOP 、 氢气 、 caesium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 81.0h， 生成 benzyl (S)-1-[(1S,2R,4R)-4-amino-2-propylcyclohexyl]-2-oxopyrrolidin-3-ylcarbamate
  参考文献：
  名称：

  Discovery of a Potent and Orally Bioavailable Dual Antagonist of CC Chemokine Receptors 2 and 5

  摘要：

  We describe the hybridization of our previously reported acyclic and cyclic CC chemokine receptor 2 (CCR2) antagonists to lead to a new series of dual antagonists of CCR2 and CCRS. Installation of a gamma-lactam as the spacer group and a quinazoline as a benzamide mimetic improved oral bioavailability markedly. These efforts led to the identification of 13d, a potent and orally bioavailable dual antagonist suitable for use in both murine and monkey models of inflammation.

  DOI：

  10.1021/ml500505q

文献信息

• Cyclic derivatives as modulators of chemokine receptor activity
  申请人：Carter H. Percy

  公开号：US20050054627A1

  公开（公告）日：2005-03-10

  The present application describes modulators of MCP-1 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the treatment of rheumatoid arthritis, multiple sclerosis, atherosclerosis and asthma.

  当前申请描述了MCP-1的调节剂，其化学公式为(I):或其药用可接受的盐形式，用于治疗类风湿性关节炎、多发性硬化症、动脉粥样硬化和哮喘。
• CYCLIC DERIVATIVES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
  申请人：Carter Percy H.

  公开号：US20090124668A1

  公开（公告）日：2009-05-14

  The present application describes modulators of MCP-1 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the treatment of rheumatoid arthritis, multiple sclerosis, atherosclerosis and asthma.

  本申请描述了 MCP-1 的调节剂，其化学式为 (I) 或其药学上可接受的盐形式，适用于治疗类风湿性关节炎、多发性硬化症、动脉粥样硬化和哮喘。
• Discovery of a Potent and Orally Bioavailable Dual Antagonist of CC Chemokine Receptors 2 and 5
  作者：Percy H. Carter、Gregory D. Brown、Robert J. Cherney、Douglas G. Batt、Jing Chen、Cheryl M. Clark、Mary Ellen Cvijic、John V. Duncia、Soo S. Ko、Sandhya Mandlekar、Ruowei Mo、David J. Nelson、Jian Pang、Anne V. Rose、Joseph B. Santella、Andrew J. Tebben、Sarah C. Traeger、Songmei Xu、Qihong Zhao、Joel C. Barrish

  DOI：10.1021/ml500505q

  日期：2015.4.9

  We describe the hybridization of our previously reported acyclic and cyclic CC chemokine receptor 2 (CCR2) antagonists to lead to a new series of dual antagonists of CCR2 and CCRS. Installation of a gamma-lactam as the spacer group and a quinazoline as a benzamide mimetic improved oral bioavailability markedly. These efforts led to the identification of 13d, a potent and orally bioavailable dual antagonist suitable for use in both murine and monkey models of inflammation.