2-benzyloxirane-2-carboxylic acid | 1190069-49-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 2-benzyloxirane-2-carboxylic acid
• CAS: 1190069-49-8
• 化学式: C₁₀H₁₀O₃
• 分子量: 178.188
• InChiKey: IPBMNAGOTODZID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-benzyloxirane-2-carboxylic acid 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Investigation of α-phenylnorstatine and α-benzylnorstatine as transition state isostere motifs in the search for new BACE-1 inhibitors

  摘要：

  Inhibition of the BACE-1 protease enzyme has over the recent decade developed into a promising drug strategy for Alzheimer therapy. In this report, more than 20 new BACE-1 protease inhibitors based on alpha-phenylnorstatine, alpha-benzylnorstatine, iso-serine, and beta-alanine moieties have been prepared. The inhibitors were synthesized by applying Fmoc solid phase methodology and evaluated for their inhibitory properties. The most potent inhibitor, tert-alcohol containing (R)-12 (IC50 = 0.19 mu M) was co-crystallized in the active site of the BACE-1 protease, furnishing a novel binding mode in which the N-terminal amine makes a hydrogen bond to one of the catalytic aspartic acids. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.11.042
• 作为产物：
  描述：

  2-benzyloxirane-2-carboxylic acid ethyl ester 在 乙醇 、 potassium hydroxide 、 盐酸 作用下， 以 乙醇 为溶剂， 反应 0.25h， 以95%的产率得到2-benzyloxirane-2-carboxylic acid
  参考文献：
  名称：

  α-取代的去甲他汀作为多种消化液空泡疟疾天冬氨酸蛋白酶抑制剂的过渡态模拟物

  摘要：

  研究了含降nor素的纤溶酶抑制剂中P1侧链从β位置移动到α位置的影响，产生了两类新的含叔醇的α-苄基去甲他汀和α-苯基去甲他汀。设计，合成和评估了十二种α-取代的诺他汀类药物对所有四种导致人类疟疾的疟原虫的消化液中存在的纤溶酶II和纤溶酶IV直向同源物（PM4）的抑制作用。已开发出新的合成路线来生产所需的α-取代的诺他汀类药物，为纯立体异构体。最好的化合物为所有PM4提供的K i值都在纳摩尔范围内，椭圆疟原虫的PM4的最佳值为110 nM。另外，获得了与密切相关的人天冬氨酸蛋白酶组织蛋白酶D的优异的选择性。通过使用线性相互作用能法（LIE）计算抑制剂与蛋白质的结合亲和力，可以合理化丧失P1取代基后对恶性疟原虫PM4的亲和力。

  DOI：

  10.1016/j.bmc.2009.06.065

文献信息

• α-Substituted norstatines as the transition-state mimic in inhibitors of multiple digestive vacuole malaria aspartic proteases
  作者：Kristina M. Orrling、Melissa R. Marzahn、Hugo Gutiérrez-de-Terán、Johan Åqvist、Ben M. Dunn、Mats Larhed

  DOI：10.1016/j.bmc.2009.06.065

  日期：2009.8

  compounds provided Ki values in the nanomolar range for all PM4, with a best value of 110 nM in PM4 from Plasmodium ovale. In addition, excellent selectivity over the closely related human aspartic protease Cathepsin D was achieved. The loss of affinity to Plasmodium falciparum PM4, which was experienced upon the move of the P1 substituent, was rationalized by the calculation of inhibitor–protein binding

  研究了含降nor素的纤溶酶抑制剂中P1侧链从β位置移动到α位置的影响，产生了两类新的含叔醇的α-苄基去甲他汀和α-苯基去甲他汀。设计，合成和评估了十二种α-取代的诺他汀类药物对所有四种导致人类疟疾的疟原虫的消化液中存在的纤溶酶II和纤溶酶IV直向同源物（PM4）的抑制作用。已开发出新的合成路线来生产所需的α-取代的诺他汀类药物，为纯立体异构体。最好的化合物为所有PM4提供的K i值都在纳摩尔范围内，椭圆疟原虫的PM4的最佳值为110 nM。另外，获得了与密切相关的人天冬氨酸蛋白酶组织蛋白酶D的优异的选择性。通过使用线性相互作用能法（LIE）计算抑制剂与蛋白质的结合亲和力，可以合理化丧失P1取代基后对恶性疟原虫PM4的亲和力。
• Investigation of α-phenylnorstatine and α-benzylnorstatine as transition state isostere motifs in the search for new BACE-1 inhibitors
  作者：Fredrik Wångsell、Patrik Nordeman、Jonas Sävmarker、Rikard Emanuelsson、Katarina Jansson、Jimmy Lindberg、Åsa Rosenquist、Bertil Samuelsson、Mats Larhed

  DOI：10.1016/j.bmc.2010.11.042

  日期：2011.1

  Inhibition of the BACE-1 protease enzyme has over the recent decade developed into a promising drug strategy for Alzheimer therapy. In this report, more than 20 new BACE-1 protease inhibitors based on alpha-phenylnorstatine, alpha-benzylnorstatine, iso-serine, and beta-alanine moieties have been prepared. The inhibitors were synthesized by applying Fmoc solid phase methodology and evaluated for their inhibitory properties. The most potent inhibitor, tert-alcohol containing (R)-12 (IC50 = 0.19 mu M) was co-crystallized in the active site of the BACE-1 protease, furnishing a novel binding mode in which the N-terminal amine makes a hydrogen bond to one of the catalytic aspartic acids. (C) 2010 Elsevier Ltd. All rights reserved.