8-(methoxycarbonyl)-1,5-dioxa-8-azaspiro[5.5]undecane-11-carboxylic acid | 1007595-10-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: 8-(methoxycarbonyl)-1,5-dioxa-8-azaspiro[5.5]undecane-11-carboxylic acid
• CAS: 1007595-10-9
• 化学式: C₁₁H₁₇NO₆
• 分子量: 259.259
• InChiKey: PADGIEWBVYKLEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.29
• 重原子数：
  18.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  85.3
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  8-(methoxycarbonyl)-1,5-dioxa-8-azaspiro[5.5]undecane-11-carboxylic acid 在 sodium azide 、 三乙胺 作用下， 以 水 、 丙酮 、 甲苯 为溶剂， 反应 5.5h， 生成 methyl 11-{[(benzyloxy)carbonyl]amino}-1,5-dioxa-8-azaspiro[5.5]undecane-8-carboxylate
  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：

  11-ethyl 8-methyl 1,5-dioxa-8-azaspiro[5.5]undecane-8,11-dicarboxylate 在 barium(II) hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 72.0h， 以89%的产率得到8-(methoxycarbonyl)-1,5-dioxa-8-azaspiro[5.5]undecane-11-carboxylic acid
  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