5-Oxo-1-(2-thiazolylmethyl)-3-pyrrolidinecarboxylic acid | 845546-27-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 5-Oxo-1-(2-thiazolylmethyl)-3-pyrrolidinecarboxylic acid
• 英文别名: 5-oxo-1-(1,3-thiazol-2-ylmethyl)pyrrolidine-3-carboxylic acid
• CAS: 845546-27-2
• 化学式: C₉H₁₀N₂O₃S
• 分子量: 226.256
• InChiKey: SHUZSNXKORKYFY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  98.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,4R)-2-[(1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-4-benzyloxypyrrolidine-1-carboxylic acid tert-butyl ester 、 5-Oxo-1-(2-thiazolylmethyl)-3-pyrrolidinecarboxylic acid 在 N-羟基-7-氮杂苯并三氮唑 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 生成 、
  参考文献：
  名称：

  Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor

  摘要：

  Based on a lead compound identified from the patent literature, we developed patentably novel BACE-1 inhibitors by introducing a cyclic amine scaffold as embodied by la and 1b. Extensive SAR studies assessed a variety of isophthalamide replacements including substituted pyrrolidinones and ultimately led to the identification of 11. Due to its favorable overall profile, 11 has been extensively profiled in various in vivo settings. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.10.053

文献信息

• CYCLIC AMINE BACE-1 INHIBITORS HAVING A HETEROCYCLIC SUBSTITUENT
  申请人：Cumming Jared N.

  公开号：US20090312341A1

  公开（公告）日：2009-12-17

  Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is X is —O—, —C(R 14 ) 2 — or —N(R)—; Z is —C(R 14 ) 2 — or —N(R)—; t is 0, 1, 2 or 3; each R and R 2 is independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, alkenyl or alkynyl; each R 14 is H, alkyl, alkenyl, alkynyl, halo, —CN, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, —OR 35 , —N(R 24 ) (R 25 ) or —SR 35 ; R 41 is alkyl, cycloalkyl, —SO 2 (alkyl), —C(O)-alkyl, —C(O)-cycloalkyl or -alkyl-NH—C(O)CH 3 ; and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I and methods of treating cognitive or neurodegenerative diseases with compounds of formula I. Also disclosed are pharmaceutical compositions and methods of treatment comprising compounds of formula I in combination with other agents useful in treating cognitive or neurodegenerative diseases.

  本发明涉及公式I的新化合物或其药学上可接受的盐或溶剂，其中R1为X为—O—，—C（R14）2—或—N（R）—；Z为—C（R14）2—或—N（R）—；t为0、1、2或3；每个R和R2独立地为H，烷基，环烷基，环烷基烷基，芳基，杂芳基，杂环烷基，芳基烷基，杂芳基烷基，杂环烷基烷基，烯基或炔基；每个R14为H，烷基，烯基，炔基，卤素，—CN，卤代烷基，环烷基，环烷基烷基，芳基，杂芳基，杂环烷基，芳基烷基，杂芳基烷基，杂环烷基烷基，—OR35，—N（R24）（R25）或—SR35；R41为烷基，环烷基，—SO2（烷基），—C（O）-烷基，—C（O）-环烷基或-烷基-NH-C（O）CH3；其余变量如规范中所定义。本发明还涉及包含公式I化合物的制药组合物以及使用公式I化合物治疗认知或神经退行性疾病的方法。本发明还涉及包含公式I化合物的制药组合物和治疗方法，其中该组合物与其他对治疗认知或神经退行性疾病有用的药物一起使用。
• US7598250B2
  申请人：——

  公开号：US7598250B2

  公开（公告）日：2009-10-06
• US7910590B2
  申请人：——

  公开号：US7910590B2

  公开（公告）日：2011-03-22