3-(1,1-dioxothiazinan-2-yl)-5-[[(1R)-1-phenylethyl]carbamoyl]benzoic acid | 911790-38-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(1,1-dioxothiazinan-2-yl)-5-[[(1R)-1-phenylethyl]carbamoyl]benzoic acid
• CAS: 911790-38-0
• 化学式: C₂₀H₂₂N₂O₅S
• 分子量: 402.471
• InChiKey: FSUAUTOBOKKIPP-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl (R)-2-((1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxypropyl)-4-benzylpiperazine-1-carboxylate 、 3-(1,1-dioxothiazinan-2-yl)-5-[[(1R)-1-phenylethyl]carbamoyl]benzoic acid 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 生成
  参考文献：
  名称：

  Piperazine sulfonamide BACE1 inhibitors: Design, synthesis, and in vivo characterization

  摘要：

  With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2' sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral A beta(40) in transgenic mice with a single subcutaneous dose. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.03.050
• 作为产物：
  描述：

  methyl 3-(1,1-dioxothiazinan-2-yl)-5-[[(1R)-1-phenylethyl]carbamoyl]benzoate 在 sodium hydroxide 、 水 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以90%的产率得到3-(1,1-dioxothiazinan-2-yl)-5-[[(1R)-1-phenylethyl]carbamoyl]benzoic acid
  参考文献：
  名称：

  新型联芳基和稠环 BACE1 抑制剂的分子建模、合成和活性研究

  摘要：

  一系列包含稠环或联芳基部分的 β-分泌酶 1 和 2 (BACE1, 2) 抑制剂的过渡态类似物经过计算设计以探测 S2 口袋，合成并测试 BACE1 和 BACE2 抑制活性。已经表明，与联芳基类似物不同，稠环部分成功地容纳在 BACE1 结合位点中，从而导致配体具有出色的抑制活性。在用瑞典人 APP 稳定转染的 N2a 细胞中，配体5b减少了 65% 的 Aβ40 产量。

  DOI：

  10.1016/j.bmcl.2008.10.096

文献信息

• [EN] BACE-2 INHIBITORY COMPOUNDS AND RELATED METHODS OF USE<br/>[FR] COMPOSÉS INHIBITEURS DE BACE-2 ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：JORTAN PHARMACEUTICALS INC

  公开号：WO2017066742A1

  公开（公告）日：2017-04-20

  Provided herein are novel compounds of Formulae I-III, and methods of using the same to selectively inhibit BACE2.

  本文提供了一种新型化合物的公式I-III，以及使用这些化合物来选择性抑制BACE2的方法。
• Substituted 1,2-ethylenediamines, Methods for Preparing Them and Uses Thereof
  申请人：Eickmeier Christian

  公开号：US20090325940A1

  公开（公告）日：2009-12-31

  The present invention relates to substituted 1,2-ethylenediamines of general formula (I) wherein the groups R 1 to R 15 , A, B, L, i as well as X 1 -X 4 are defined as in the specification and claims and the use thereof for the treatment of Alzheimer's disease (AD) and similar diseases.
• SUBSTITUTED 1,2-ETHYLENEDIAMINES, METHODS FOR PREPARING THEM AND USES THEREOF
  申请人：EICKMEIER Christian

  公开号：US20100204160A1

  公开（公告）日：2010-08-12

  The present invention relates to substituted 1,2-ethylenediamines of general formula (I) wherein the groups R 1 to R 15 , A, B, L, i as well as X 1 -X 4 are defined as in the specification and claims and the use thereof for the treatment of Alzheimer's disease (AD) and similar diseases.
• US7713961B2
  申请人：——

  公开号：US7713961B2

  公开（公告）日：2010-05-11
• Piperazine sulfonamide BACE1 inhibitors: Design, synthesis, and in vivo characterization
  作者：Jared Cumming、Suresh Babu、Ying Huang、Carolyn Carrol、Xia Chen、Leonard Favreau、William Greenlee、Tao Guo、Matthew Kennedy、Reshma Kuvelkar、Thuy Le、Guoqing Li、Nansie McHugh、Peter Orth、Lynne Ozgur、Eric Parker、Kurt Saionz、Andrew Stamford、Corey Strickland、Dawit Tadesse、Johannes Voigt、Lili Zhang、Qi Zhang

  DOI：10.1016/j.bmcl.2010.03.050

  日期：2010.5

  With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2' sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral A beta(40) in transgenic mice with a single subcutaneous dose. (C) 2010 Elsevier Ltd. All rights reserved.