ethyl (3RS,4SR)-4-amino-3-methoxypiperidine-1-carboxylic acid hydrochloride Salt | 83863-71-2

• 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: ethyl (3RS,4SR)-4-amino-3-methoxypiperidine-1-carboxylic acid hydrochloride Salt
• 英文别名: Ethyl cis-4-amino-3-methoxypiperidine-1-carboxylate monohydrochloride；ethyl (3S,4R)-4-amino-3-methoxypiperidine-1-carboxylate;hydrochloride
• CAS: 83863-71-2
• 化学式: C₉H₁₈N₂O₃*ClH
• 分子量: 238.714
• InChiKey: JUIQWDFWJKAYQH-WLYNEOFISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.52
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  66.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl (3RS,4SR)-4-amino-3-methoxypiperidine-1-carboxylic acid hydrochloride Salt 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 甲酸铵 、 碳酸氢钠 作用下， 以 甲醇 、 水 为溶剂， 反应 14.0h， 生成 ethyl (-)-cis-4-amino-3-methoxy-1-piperidinecarboxylate
  参考文献：
  名称：

  Optimization of Pyrrolamide Topoisomerase II Inhibitors Toward Identification of an Antibacterial Clinical Candidate (AZD5099)

  摘要：

  AZD5099 (compound 63) is an antibacterial agent that entered phase 1 clinical trials targeting infections caused by Gram-positive and fastidious Gram-negative bacteria. It was derived from previously reported pyrrolamide antibacterials and a fragment-based approach targeting the ATP binding site of bacterial type II topoisomerases. The program described herein varied a 3-piperidine substituent and incorporated 4-thiazole substituents that form a seven-membered ring intramolecular hydrogen bond with a 5-position carboxylic acid. Improved antibacterial activity and lower in vivo clearances were achieved. The lower clearances were attributed, in part, to reduced recognition by the multidrug resistant transporter Mrp2. Compound 63 showed notable efficacy in a mouse neutropenic Staphylococcus aureus infection model. Resistance frequency versus the drug was low, and reports of clinical resistance due to alteration of the target are few. Hence, 63 could offer a novel treatment for serious issues of resistance to currently used antibacterials.

  DOI：

  10.1021/jm500462x
• 作为产物：
  描述：

  3,4,4-三甲氧基哌啶-1-羧酸乙酯 在 硫酸 、 palladium 10% on activated carbon 、 甲酸铵 、 三乙酰氧基硼氢化钠 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 2.5h， 生成 ethyl (3RS,4SR)-4-amino-3-methoxypiperidine-1-carboxylic acid hydrochloride Salt
  参考文献：
  名称：

  Optimization of Pyrrolamide Topoisomerase II Inhibitors Toward Identification of an Antibacterial Clinical Candidate (AZD5099)

  摘要：

  AZD5099 (compound 63) is an antibacterial agent that entered phase 1 clinical trials targeting infections caused by Gram-positive and fastidious Gram-negative bacteria. It was derived from previously reported pyrrolamide antibacterials and a fragment-based approach targeting the ATP binding site of bacterial type II topoisomerases. The program described herein varied a 3-piperidine substituent and incorporated 4-thiazole substituents that form a seven-membered ring intramolecular hydrogen bond with a 5-position carboxylic acid. Improved antibacterial activity and lower in vivo clearances were achieved. The lower clearances were attributed, in part, to reduced recognition by the multidrug resistant transporter Mrp2. Compound 63 showed notable efficacy in a mouse neutropenic Staphylococcus aureus infection model. Resistance frequency versus the drug was low, and reports of clinical resistance due to alteration of the target are few. Hence, 63 could offer a novel treatment for serious issues of resistance to currently used antibacterials.

  DOI：

  10.1021/jm500462x

文献信息

• PRACTICAL SYNTHESIS OF ETHYL<i>CIS</i>-4-AMINO-3-METHOXY-1-PIPERIDINE CARBOXYLATE, A KEY INTERMEDIATE OF CISAPRIDE
  作者：Bong J. Kim、Do K. Pyun、Hee J. Jung、Hyun J. Kwak、Jae H. Kim、Eun J. Kim、Won J. Jeong、Cheol H. Lee

  DOI：10.1081/scc-100103541

  日期：2001.1

  A practical synthesis of ethyl cis-4-amino-3-methoxy-1-piperidinecarboxylate 1, a key intermediate of cisapride as a potent gastrointestinal stimulant, has been accomplished from 1-methyl-1,2,3,6-tetrahydropyridine 2 via an efficient formation of cis-fused oxazolidinopiperidine 7.

  顺式-4-氨基-3-甲氧基-1-哌啶羧酸乙酯 1 的实用合成是西沙必利的关键中间体，作为一种有效的胃肠刺激剂，已通过 1-甲基-1,2,3,6-四氢吡啶 2 完成顺式稠合恶唑烷并哌啶 7 的有效形成。
• Optimization of Pyrrolamide Topoisomerase II Inhibitors Toward Identification of an Antibacterial Clinical Candidate (AZD5099)
  作者：Gregory S. Basarab、Pamela J. Hill、C. Edwin Garner、Ken Hull、Oluyinka Green、Brian A. Sherer、P. Brian Dangel、John I. Manchester、Shanta Bist、Sheila Hauck、Fei Zhou、Maria Uria-Nickelsen、Ruth Illingworth、Richard Alm、Mike Rooney、Ann E. Eakin

  DOI：10.1021/jm500462x

  日期：2014.7.24

  AZD5099 (compound 63) is an antibacterial agent that entered phase 1 clinical trials targeting infections caused by Gram-positive and fastidious Gram-negative bacteria. It was derived from previously reported pyrrolamide antibacterials and a fragment-based approach targeting the ATP binding site of bacterial type II topoisomerases. The program described herein varied a 3-piperidine substituent and incorporated 4-thiazole substituents that form a seven-membered ring intramolecular hydrogen bond with a 5-position carboxylic acid. Improved antibacterial activity and lower in vivo clearances were achieved. The lower clearances were attributed, in part, to reduced recognition by the multidrug resistant transporter Mrp2. Compound 63 showed notable efficacy in a mouse neutropenic Staphylococcus aureus infection model. Resistance frequency versus the drug was low, and reports of clinical resistance due to alteration of the target are few. Hence, 63 could offer a novel treatment for serious issues of resistance to currently used antibacterials.