2-[(3S,4R)-4-[(3,4-dichloro-5-methyl-1H-pyrrole-2-carbonyl)amino]-3-fluoro-1-piperidyl]thiazole-5-carboxylate | 907539-79-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-[(3S,4R)-4-[(3,4-dichloro-5-methyl-1H-pyrrole-2-carbonyl)amino]-3-fluoro-1-piperidyl]thiazole-5-carboxylate
• 英文别名: 2-((3S,4R)-4-([(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino)-3-fluoropiperidin-1-yl)-1,3-thiazole-5-carboxylic acid；2-[(3S,4R)-4-[(3,4-dichloro-5-methyl-1H-pyrrole-2-carbonyl)amino]-3-fluoropiperidin-1-yl]-1,3-thiazole-5-carboxylic acid
• CAS: 907539-79-1
• 化学式: C₁₅H₁₅Cl₂FN₄O₃S
• 分子量: 421.28
• InChiKey: BGDGHNSKANYMHF-JGVFFNPUSA-N

物化性质

• 密度：
  1.63±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  127
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-[(3S,4R)-4-[(3,4-dichloro-5-methyl-1H-pyrrole-2-carbonyl)amino]-3-fluoro-1-piperidyl]thiazole-5-carboxylate 在 氢氧化钾 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 生成 potassium 2-((3S,4R)-4-([(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino)-3-fluoropiperidin-1-yl)-1,3-thiazole-5-carboxylate
  参考文献：
  名称：

  [EN] ANTIBACTERIAL PIPERIDINE DERIVATIVES
  [FR] COMPOSÉS ANTIBACTÉRIENS DÉRIVÉS DE PIPÉRIDINE

  摘要：

  公式（I）的化合物及其药用盐被描述：公式（I）。还描述了它们的制备方法、含有它们的药物组成物、作为药物的用途以及在治疗细菌感染中的用途。

  公开号：

  WO2006087543A1
• 作为产物：
  描述：

  3,4-dichloro-N-[(3R,4S)-3-fluoropiperidin-4-yl]-5-methyl-1H-pyrrole-2-carboxamide hydrochloride 在 三乙胺 、 sodium hydroxide 作用下， 以 N-甲基吡咯烷酮 、 水 为溶剂， 反应 0.33h， 生成 2-[(3S,4R)-4-[(3,4-dichloro-5-methyl-1H-pyrrole-2-carbonyl)amino]-3-fluoro-1-piperidyl]thiazole-5-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

文献信息

• Pyrrolamide DNA gyrase inhibitors: Optimization of antibacterial activity and efficacy
  作者：Brian A. Sherer、Kenneth Hull、Oluyinka Green、Gregory Basarab、Sheila Hauck、Pamela Hill、James T. Loch、George Mullen、Shanta Bist、Joanna Bryant、Ann Boriack-Sjodin、Jon Read、Nancy DeGrace、Maria Uria-Nickelsen、Ruth N. Illingworth、Ann E. Eakin

  DOI：10.1016/j.bmcl.2011.10.010

  日期：2011.12

  The pyrrolamides are a new class of antibacterial agents targeting DNA gyrase, an essential enzyme across bacterial species and inhibition results in the disruption of DNA synthesis and subsequently, cell death. The optimization of biochemical activity and other drug-like properties through substitutions to the pyrrole, piperidine, and heterocycle portions of the molecule resulted in pyrrolamides with

  吡咯酰胺是一类针对DNA促旋酶的新型抗菌剂，DNA促旋酶是一种跨细菌物种的必不可少的酶，抑制作用会破坏DNA的合成，进而导致细胞死亡。通过取代分子的吡咯，哌啶和杂环部分来优化生化活性和其他类似药物的特性，可得到具有改善的细胞活性和体内功效的吡咯酰胺。
• ANTIBACTERIAL PIPERDINE DERIVATIVES
  申请人：Basarab Gregory

  公开号：US20100179150A1

  公开（公告）日：2010-07-15

  Compounds of formula (I) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described.

  描述了化学式（I）的化合物及其药学上可接受的盐。描述了制备它们的过程，含有它们的药物组合物，它们作为药物的用途以及它们在治疗细菌感染中的用途。
• CHEMICAL COMPOUNDS
  申请人：AstraZeneca, Intellectual Property

  公开号：US20130150366A1

  公开（公告）日：2013-06-13

  Compounds of formula (I) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use in the treatment of bacterial infections are also described.

  本文描述了化学式(I)的化合物及其药学上可接受的盐。还描述了制备它们的过程、含有它们的制药组合物，以及它们在治疗细菌感染方面的用途。
• Antibacterial piperdine derivatives
  申请人：Basarab Gregory

  公开号：US08399489B2

  公开（公告）日：2013-03-19

  Compounds of formula (I) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described.

  本文描述了公式(I)的化合物及其药学上可接受的盐。同时还描述了它们的制备过程、包含它们的药物组合物、它们作为药物的用途以及它们在治疗细菌感染方面的应用。
• ANTIBACTERIAL PIPERIDINE DERIVATIVES
  申请人：AstraZeneca AB

  公开号：EP1853586B1

  公开（公告）日：2013-07-24