(S)-3-叠氮基-1-吡咯烷羧酸苯甲酯 | 122536-70-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (S)-3-叠氮基-1-吡咯烷羧酸苯甲酯
• 英文名称: (S)-3-azido-1-pyrrolidinecarboxylic acid phenylmethyl ester
• 英文别名: (S)-3-Azido-1-pyrrolidinecarboxylic acid, phenylmethyl ester；benzyl (3S)-3-azidopyrrolidine-1-carboxylate
• CAS: 122536-70-3
• 化学式: C₁₂H₁₄N₄O₂
• 分子量: 246.269
• InChiKey: WEHHDTHUEKWVKL-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  43.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-3-叠氮基-1-吡咯烷羧酸苯甲酯 在 镍 氢气 作用下， 以 甲醇 为溶剂， 21.5~25.0 ℃ 、344.73 kPa 条件下， 反应 21.5h， 以95%的产率得到(S)-(+)-1-Cbz-3-氨基吡咯烷
  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
• 作为产物：
  描述：

  (R)-3-<(methylsulfonyl)oxy>-1-pyrrolidinecarboxylic acid phenylmethyl ester 在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以98%的产率得到(S)-3-叠氮基-1-吡咯烷羧酸苯甲酯
  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

• [EN] PYRROLOPYRIDAZINE JAK3 INHIBITORS AND THEIR USE FOR THE TREATMENT OF INFLAMMATORY AND AUTOIMMUNE DISEASES<br/>[FR] INHIBITEURS DE JAK3 DE TYPE PYRROLOPYRIDAZINE ET LEUR UTILISATION POUR TRAITER LES MALADIES INFLAMMATOIRES ET AUTO-IMMUNES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2012125893A1

  公开（公告）日：2012-09-20

  The present invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase activity of JAK3, thereby making them useful for the treatment of inflammatory and autoimmune diseases.

  本发明提供了化合物I的公式及其药学上可接受的盐。公式I的化合物抑制JAK3的酪氨酸激酶活性，因此使它们在治疗炎症和自身免疫性疾病方面具有用途。
• (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.

  本文介绍了一种小说(S)-7-(3-氨基-1-吡咯烷基)-1-环丙基-6-氟-1,4-二氢-4-氧-1,8-萘啶-3-羧酸，其低烷基酯和药学上可接受的盐，以及其制造、配方和用于治疗细菌感染的方法。
• Naphthyridine antibacterial agents containing an .alpha.-amino acid in
  申请人：Warner-Lambert Company

  公开号：US04851418A1

  公开（公告）日：1989-07-25

  Novel quinolone and naphthyridine antibacterial agents are herein described having improved in vivo activity both orally and subcutaneously where the 7-side chain of such compounds contain an .alpha.-amino acid; also described are its corresponding optical isomers, methods of preparation as well as compositions and methods of treating infections diseases.

  本文描述了一种新型的喹诺酮和萘啶类抗菌剂，其具有口服和皮下注射的改善体内活性，其中这些化合物的7侧链包含一种α-氨基酸。同时还描述了其相应的光学异构体、制备方法以及治疗感染性疾病的组合物和方法。
• SANCHEZ, JOSEPH P.
  作者：SANCHEZ, JOSEPH P.

  DOI：——

  日期：——
• PYRROLOPYRIDAZINE JAK3 INHIBITORS AND THEIR USE FOR THE TREATMENT OF INFLAMMATORY AND AUTOIMMUNE DISEASES
  申请人：Bristol-Myers Squibb Company

  公开号：EP2686321B1

  公开（公告）日：2016-11-16