2-[(3S,4R)-4-[(3,4-dichloro-5-methyl-1H-pyrrole-2-carbonyl)-amino]-3-methoxy-1-piperidyl]-4-[[(1S)-2-methoxy-1-methylethyl]carbamoyl]thiazole-5-carboxylic acid | 907543-25-3

• 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-methoxy-1-piperidyl]-4-[[(1S)-2-methoxy-1-methylethyl]carbamoyl]thiazole-5-carboxylic acid
• 英文别名: AZD5099；2-((3S,4R)-4-([(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino)-3-methoxypiperidin-1-yl)-4-(([(1S)-2-methoxy-1-methylethyl]amino)carbonyl)-1,3-thiazole-5-carboxylic acid；5-Thiazolecarboxylic acid, 2-((3S,4R)-4-(((3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl)amino)-3-methoxy-1-piperidinyl)-4-((((1S)-2-methoxy-1-methylethyl)amino)carbonyl)-；2-[(3S,4R)-4-[(3,4-dichloro-5-methyl-1H-pyrrole-2-carbonyl)amino]-3-methoxypiperidin-1-yl]-4-[[(2S)-1-methoxypropan-2-yl]carbamoyl]-1,3-thiazole-5-carboxylic acid
• CAS: 907543-25-3
• 化学式: C₂₁H₂₇Cl₂N₅O₆S
• 分子量: 548.447
• InChiKey: KGZHRAVDXGQUQM-WCQGTBRESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  174
• 氢给体数：
  4
• 氢受体数：
  9

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-methoxy-1-piperidyl]-4-[[(1S)-2-methoxy-1-methylethyl]carbamoyl]thiazole-5-carboxylic acid 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 生成 sodium 2-[(3S,4R)-4-[(3,4-dichloro-5-methyl-1H-pyrrole-2-carbonyl)amino]-3-methoxy-1-piperidyl]-4-[[(1S)-2-methoxy-1-methyl-ethyl]carbamoyl]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
• 作为产物：
  描述：

  ethyl 2-[(3S,4R)-4-[(3,4-dichloro-5-methyl-1H-pyrrole-2-carbonyl)amino]-3-methoxy-1-piperidyl]-4-[[(1S)-2-methoxy-1-methyl-ethyl]carbamoyl]thiazole-5-carboxylate 在 barium(II) hydroxide 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以95%的产率得到2-[(3S,4R)-4-[(3,4-dichloro-5-methyl-1H-pyrrole-2-carbonyl)-amino]-3-methoxy-1-piperidyl]-4-[[(1S)-2-methoxy-1-methylethyl]carbamoyl]thiazole-5-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

文献信息

• QUINAZOLINE DERIVATIVES AS P13 KINASE INHIBITORS
  申请人：ADAMS Nicholas D.

  公开号：US20090018131A1

  公开（公告）日：2009-01-15

  Invented is a method of inhibiting the activity/function of PI3 kinases using quinazoline derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of quinazoline derivatives.

  本发明涉及使用喹唑啉衍生物来抑制PI3激酶的活性/功能的方法。本发明还涉及使用喹唑啉衍生物治疗以下一种或多种疾病状态的方法：自身免疫性疾病、炎症性疾病、心血管疾病、神经退行性疾病、过敏、哮喘、胰腺炎、多器官衰竭、肾脏疾病、血小板聚集、癌症、精子运动能力、移植排斥、移植物排斥和肺部损伤。通过给予喹唑啉衍生物进行治疗。
• 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。
• [EN] PYRROLE ACYL PIPERYLHYDRAZINE COMPOUND AND USE THEREOF<br/>[FR] COMPOSÉ PYRROLE ACYLE PIPÉRAZINYLHYDRAZINE ET SON UTILISATION<br/>[ZH] 吡咯酰哌啶胺类化合物及其用途
  申请人：[en]INSTITUTE OF MATERIA MEDICA ,CHINESE ACADEMY OF MEDICAL SCICENCES;[zh]中国医学科学院药物研究所

  公开号：WO2022258038A1

  公开（公告）日：2022-12-15

  本发明属于抗菌药物技术领域，公开了吡咯酰哌啶胺类化合物及其用途。具体涉及吡咯酰哌啶胺类化合物与其药学上可接受的盐及其在制备抗菌、抗支原体或者抗衣原体感染药物中的用途。所述化合物具有如下通式所示的结构：
• ANTIBACTERIAL PIPERIDINE DERIVATIVES
  申请人：AstraZeneca AB

  公开号：EP1853586B1

  公开（公告）日：2013-07-24