2-[(3S)-3-[(6-chloronaphthalen-2-yl)sulfonylamino]-2-oxopiperidin-1-yl]acetic acid | 445280-46-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-[(3S)-3-[(6-chloronaphthalen-2-yl)sulfonylamino]-2-oxopiperidin-1-yl]acetic acid
• CAS: 445280-46-6
• 化学式: C₁₇H₁₇ClN₂O₅S
• 分子量: 396.851
• InChiKey: ZZEPRUJFLKACOY-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[(3S)-3-[(6-chloronaphthalen-2-yl)sulfonylamino]-2-oxopiperidin-1-yl]acetic acid 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 6-chloro-N-[(3S)-2-oxo-1-[2-oxo-2-[7-(piperidine-4-carbonyl)-3,7-diazabicyclo[3.3.1]nonan-3-yl]ethyl]piperidin-3-yl]naphthalene-2-sulfonamide
  参考文献：
  名称：

  Arylsulfonamidopiperidone derivatives as a novel class of factor Xa inhibitors

  摘要：

  The design, synthesis and SAR of a novel class of valerolactam-based arylsulfonamides as potent and selective FXa inhibitors is reported. The arylsulfonamide-valerolactam scaffold was derived based on the proposed bioisosterism to the arylcyanoguanidine-caprolactam core in known FXa inhibitors. The SAR study led to compound 46 as the most potent FXa inhibitor in this series, with an IC50 of 7 nM and EC2xPT of 1.7 mu M. The X-ray structure of compound 40 bound to FXa shows that the sulfonamide-valerolactam scaffold anchors the aryl group in the S1 and the novel acylcytisine pharmacophore in the S4 pockets. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.098
• 作为产物：
  描述：

  (S)-2-(3-(叔丁氧羰基氨基)-2-氧代哌啶-1-基)乙酸 在 盐酸 、 lithium hydroxide monohydrate 、 水 、 碳酸氢钠 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 生成 2-[(3S)-3-[(6-chloronaphthalen-2-yl)sulfonylamino]-2-oxopiperidin-1-yl]acetic acid
  参考文献：
  名称：

  Arylsulfonamidopiperidone derivatives as a novel class of factor Xa inhibitors

  摘要：

  The design, synthesis and SAR of a novel class of valerolactam-based arylsulfonamides as potent and selective FXa inhibitors is reported. The arylsulfonamide-valerolactam scaffold was derived based on the proposed bioisosterism to the arylcyanoguanidine-caprolactam core in known FXa inhibitors. The SAR study led to compound 46 as the most potent FXa inhibitor in this series, with an IC50 of 7 nM and EC2xPT of 1.7 mu M. The X-ray structure of compound 40 bound to FXa shows that the sulfonamide-valerolactam scaffold anchors the aryl group in the S1 and the novel acylcytisine pharmacophore in the S4 pockets. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.098

文献信息

• Sulfonamide lactam inhibitors of FXa and method
  申请人：——

  公开号：US20040186134A1

  公开（公告）日：2004-09-23

  Sulfonamide lactams of the following formula 1 wherein X, R 1 , R 2 , R 3 , R 4 , R 4a , R 5 , R 5a , R 6 , R 6a , R 7 and R 8 are as described herein, are provided which inhibitors of Factor Xa and are useful as anticoagulants in the treatment of cardiovascular diseases associated with thromboses.

  以下式子中的磺胺酰胺内酰胺，其中X、R1、R2、R3、R4、R4a、R5、R5a、R6、R6a、R7和R8如本文所述，被提供为因子Xa的抑制剂，并且在治疗与血栓相关的心血管疾病中作为抗凝剂是有用的。
• US7166586B2
  申请人：——

  公开号：US7166586B2

  公开（公告）日：2007-01-23
• Arylsulfonamidopiperidone derivatives as a novel class of factor Xa inhibitors
  作者：Yan Shi、Stephen P. O’Connor、Doree Sitkoff、Jing Zhang、Mengxiao Shi、Sharon N. Bisaha、Ying Wang、Chi Li、Zheming Ruan、R. Michael Lawrence、Herbert E. Klei、Kevin Kish、Eddie C.-K. Liu、Steve M. Seiler、Liang Schweizer、Thomas E. Steinbacher、William A. Schumacher、Jeffrey A. Robl、John E. Macor、Karnail S. Atwal、Philip D. Stein

  DOI：10.1016/j.bmcl.2011.06.098

  日期：2011.12

  The design, synthesis and SAR of a novel class of valerolactam-based arylsulfonamides as potent and selective FXa inhibitors is reported. The arylsulfonamide-valerolactam scaffold was derived based on the proposed bioisosterism to the arylcyanoguanidine-caprolactam core in known FXa inhibitors. The SAR study led to compound 46 as the most potent FXa inhibitor in this series, with an IC50 of 7 nM and EC2xPT of 1.7 mu M. The X-ray structure of compound 40 bound to FXa shows that the sulfonamide-valerolactam scaffold anchors the aryl group in the S1 and the novel acylcytisine pharmacophore in the S4 pockets. (C) 2011 Elsevier Ltd. All rights reserved.