(S)-7-(3-tertbutoxycarbonylamino-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid | 127934-52-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (S)-7-(3-tertbutoxycarbonylamino-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid
• 英文别名: (S)-1-Cyclopropyl-7-[3-[[(1,1-dimethylethoxy)carbonyl]-amino]-1-pyrrolidinyl]-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid；1-cyclopropyl-6-fluoro-7-[(3S)-3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]-4-oxo-1,8-naphthyridine-3-carboxylic acid
• CAS: 127934-52-5
• 化学式: C₂₁H₂₅FN₄O₅
• 分子量: 432.452
• InChiKey: ZVPWXQHLRXNEAA-NSHDSACASA-N

物化性质

• 沸点：
  653.0±55.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (S)-7-(3-tertbutoxycarbonylamino-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid 在 盐酸 作用下， 以 乙醇 为溶剂， 生成 PD131628-00028
  参考文献：
  名称：

  (S)-7-(3-amino-1-pyrrolidinyl)-1-cyclop

  摘要：

  该小说描述了(S)-7-(3-氨基-1-吡咯啉基)-1-环丙基-6-氟-1,4-二氢-4-氧基-1,8-n-邻菲啉-3-羧酸，其较低的烷基酯和药用盐，以及其制备、配方和用于治疗细菌感染的方法。

  公开号：

  US04916141A1
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 三乙胺 作用下， 以 甲醇 、 乙腈 、 叔丁醇 为溶剂， 21.0~25.0 ℃ 、348.88 kPa 条件下， 反应 3.5h， 生成 (S)-7-(3-tertbutoxycarbonylamino-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid
  参考文献：
  名称：

  Quinolone antibacterial agents. Synthesis and structure-activity relationships of a series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)quinolones. Highly soluble quinolone prodrugs with in vivo pseudomonas activity

  摘要：

  A series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)-6-fluoro-1,8-naphthyridine-3-carboxylic acids, 1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids, 1-cyclopropyl-6-fluoro-3-quinolinecarboxylic acids, and 5-amino-1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids have been prepared and evaluated for comparative antibacterial activity. Compounds were prepared by acylation of the 3-amino group of the pyrrolidine with common amino acids using standard peptide chemistry. This series has been compared with the parent compounds for antibacterial activity in vitro and in vivo as well as for comparatively solubility. The amino acid analogues were less active in vitro, but had equal or increased efficacy in vivo. Indeed, it was proven that these compounds, which were stable to acid and base under the reaction conditions for their preparation, were rapidly cleaved in serum to give the parent quinolones. The amino acid derivatives showed a 3-70 times improved solubility when compared to the parent compounds. The most active compound of the series was [S-(R*,R*)]-7-[3-[2-amino-1-oxopropyl)-amino]-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (PD 131112).

  DOI：

  10.1021/jm00088a011

文献信息

• Lectin-Targeted Prodrugs Activated by <i>Pseudomonas aeruginosa</i> for Self-Destructive Antibiotic Release
  作者：Joscha Meiers、Katharina Rox、Alexander Titz

  DOI：10.1021/acs.jmedchem.2c01214

  日期：2022.10.27

  can be exploited for targeted drug delivery. In this work, several fluoroquinolones were conjugated to lectin probes by cleavable peptide linkers to yield lectin-targeted prodrugs. Mechanistically, these conjugates therefore remain non-toxic in the systemic distribution and will be activated to kill only once they have accumulated at the infection site. The synthesized prodrugs proved stable in the

  慢性铜绿假单胞菌感染的特征是生物膜形成，这是铜绿假单胞菌的主要毒力因子和广泛耐药性的原因。氟喹诺酮类药物是有效的抗生素，但与严重的副作用有关。两个细胞外铜绿假单胞菌特异性凝集素 LecA 和 LecB 是生物膜的关键结构成分，可用于靶向药物递送。在这项工作中，几种氟喹诺酮类药物通过可裂解的肽接头与凝集素探针结合，产生凝集素靶向前药。因此，从机制上讲，这些缀合物在全身分布中保持无毒，并且只有在它们在感染部位积聚后才会被激活以杀死。合成的前药在宿主血浆和肝脏代谢存在的情况下被证明是稳定的，但在铜绿假单胞菌存在的情况下迅速释放抗生素货物在体外以自我毁灭的方式。此外，前药在体外显示出良好的吸收、分布、代谢和消除 (ADME) 特性并降低了毒性，从而建立了第一个针对铜绿假单胞菌的凝集素靶向抗生素前药。
• (S)-7-(3-Amino-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0394685A2

  公开（公告）日：1990-10-31

  The novel (S)-7-(3-amino-1-pyrrolidinyl)-1-cyclo­propyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-­3-carboxylic acid, lower alkyl esters and pharmaceutically acceptable salts thereof are described as well as a method for its manufacture, formulation, and use in treating bacterial infections.

  介绍了新型 (S)-7-(3-氨基-1-吡咯烷基)-1-环丙基-6-氟-1,4-二氢-4-氧代-1,8-萘啶-3-羧酸、低级烷基酯及其药学上可接受的盐类，以及其生产、配制和用于治疗细菌感染的方法。
• US4916141A
  申请人：——

  公开号：US4916141A

  公开（公告）日：1990-04-10
• Quinolone antibacterial agents. Synthesis and structure-activity relationships of a series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)quinolones. Highly soluble quinolone prodrugs with in vivo pseudomonas activity
  作者：Joseph P. Sanchez、John M. Domagala、Carl L. Heifetz、Stephen R. Priebe、Josephine A. Sesnie、Ashok K. Trehan

  DOI：10.1021/jm00088a011

  日期：1992.5

  A series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)-6-fluoro-1,8-naphthyridine-3-carboxylic acids, 1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids, 1-cyclopropyl-6-fluoro-3-quinolinecarboxylic acids, and 5-amino-1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids have been prepared and evaluated for comparative antibacterial activity. Compounds were prepared by acylation of the 3-amino group of the pyrrolidine with common amino acids using standard peptide chemistry. This series has been compared with the parent compounds for antibacterial activity in vitro and in vivo as well as for comparatively solubility. The amino acid analogues were less active in vitro, but had equal or increased efficacy in vivo. Indeed, it was proven that these compounds, which were stable to acid and base under the reaction conditions for their preparation, were rapidly cleaved in serum to give the parent quinolones. The amino acid derivatives showed a 3-70 times improved solubility when compared to the parent compounds. The most active compound of the series was [S-(R*,R*)]-7-[3-[2-amino-1-oxopropyl)-amino]-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (PD 131112).
• (S)-7-(3-amino-1-pyrrolidinyl)-1-cyclop
  申请人：Warner-Lambert Company

  公开号：US04916141A1

  公开（公告）日：1990-04-10

  The novel (S)-7-(3-amino-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1, 8-n phthyridine-3-carboxylic acid, lower alkyl esters and pharmaceutically acceptable salts thereof are described as well as a method for its manufacture, formulation, and use in treating bacterial infections.

  该小说描述了(S)-7-(3-氨基-1-吡咯啉基)-1-环丙基-6-氟-1,4-二氢-4-氧基-1,8-n-邻菲啉-3-羧酸，其较低的烷基酯和药用盐，以及其制备、配方和用于治疗细菌感染的方法。