1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-[4-(1-acetoxyethoxycarbonyl)-1-piperazinyl]-3-quinolinecarboxylic acid | 99106-35-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-[4-(1-acetoxyethoxycarbonyl)-1-piperazinyl]-3-quinolinecarboxylic acid
• 英文别名: 7-[4-(1-Acetyloxyethoxycarbonyl)piperazin-1-yl]-1-ethyl-6-fluoro-4-oxoquinoline-3-carboxylic acid
• CAS: 99106-35-1
• 化学式: C₂₁H₂₄FN₃O₇
• 分子量: 449.436
• InChiKey: CBVLYNWYKXAQDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  诺氟沙星 在 Proton Sponge 作用下， 以 氯仿 、 溶剂黄146 为溶剂， 反应 88.0h， 生成 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-[4-(1-acetoxyethoxycarbonyl)-1-piperazinyl]-3-quinolinecarboxylic acid
  参考文献：
  名称：

  (Acyloxy)alkyl carbamate prodrugs of norfloxacin

  摘要：

  As a new prodrug approach to norfloxacin (NFLX) we prepared the acetoxyalkyl carbamates of the type NFLXCO-OCHR-OAc by the reaction of sodium or mercuric acetate on NFLX alpha-chloroalkyl carbamates. These prodrugs did not have the bitter taste of NFLX. In vitro, the acetoxyethyl carbamate exhibited activity only against Staphylococcus spp. and was inactive against Gram-negative organisms. However, in the presence of serum and intestinal homogenate, esterase-catalyzed hydrolysis of the ester bond in these modified carbamates led to a cascade reaction resulting in the rapid regeneration of NFLX. At high oral doses of the prodrug, the acetaldehyde produced as a side product in the breakdown of the promoiety caused a slight decrease in alcohol metabolism in a mouse model. The bioavailability of NFLX from the acetoxyethyl carbamate was lower compared to an equivalent dose of NFLX when given as an oral suspension in rhesus monkeys, presumably because of the lower aqueous solubility of the prodrug.

  DOI：

  10.1021/jm00105a013

文献信息

• (Acyloxyalkoxy) carbonyl derivatives as bioreversible prodrug moieties for primary and secondary amine functions in drugs, their preparation and pharmaceutical compositions containing said derivatives
  申请人：Merck & Co., Inc.

  公开号：EP0130119A2

  公开（公告）日：1985-01-02

  This invention relates to novel (acyloxyalkoxy) carbonyl derivatives as a bioreversible prodrug moieties for primary and secondary amine functions in drugs having a primary or secondary amine function thereon. Hydrolytic enzymes are used to trigger the regeneration of the parent amine drug of the carbamate prodrug moiety. The case also contains pharmaceutical composition, method of treatment and process claims.

  本发明涉及新型（酰氧基烷氧基）羰基衍生物，作为具有伯胺或仲胺功能的药物中伯胺和仲胺功能的生物可逆原药分子。使用水解酶可促使氨基甲酸酯原药分子的母胺药物再生。本案还包含药物组合物、治疗方法和工艺权利要求。
• ALEXANDER, JOSE;FROMTLING, ROBERT A.;BLAND, JUDITH A.;PELAK, BARBARA A.;G+, J. MED. CHEM., 34,(1991) N, C. 78-81
  作者：ALEXANDER, JOSE、FROMTLING, ROBERT A.、BLAND, JUDITH A.、PELAK, BARBARA A.、G+

  DOI：——

  日期：——
• US4760057A
  申请人：——

  公开号：US4760057A

  公开（公告）日：1988-07-26
• (Acyloxy)alkyl carbamate prodrugs of norfloxacin
  作者：Jose Alexander、Robert A. Fromtling、Judith A. Bland、Barbara A. Pelak、Evamarie C. Gilfillan

  DOI：10.1021/jm00105a013

  日期：1991.1

  As a new prodrug approach to norfloxacin (NFLX) we prepared the acetoxyalkyl carbamates of the type NFLXCO-OCHR-OAc by the reaction of sodium or mercuric acetate on NFLX alpha-chloroalkyl carbamates. These prodrugs did not have the bitter taste of NFLX. In vitro, the acetoxyethyl carbamate exhibited activity only against Staphylococcus spp. and was inactive against Gram-negative organisms. However, in the presence of serum and intestinal homogenate, esterase-catalyzed hydrolysis of the ester bond in these modified carbamates led to a cascade reaction resulting in the rapid regeneration of NFLX. At high oral doses of the prodrug, the acetaldehyde produced as a side product in the breakdown of the promoiety caused a slight decrease in alcohol metabolism in a mouse model. The bioavailability of NFLX from the acetoxyethyl carbamate was lower compared to an equivalent dose of NFLX when given as an oral suspension in rhesus monkeys, presumably because of the lower aqueous solubility of the prodrug.