N-((tetrahydro-4H-pyran-4-yloxy)carbonyl)-L-leucine N-hydroxysuccinimide ester | 854402-76-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-((tetrahydro-4H-pyran-4-yloxy)carbonyl)-L-leucine N-hydroxysuccinimide ester
• 英文别名: (2,5-dioxopyrrolidin-1-yl) (2S)-4-methyl-2-(oxan-4-yloxycarbonylamino)pentanoate
• CAS: 854402-76-9
• 化学式: C₁₆H₂₄N₂O₇
• 分子量: 356.376
• InChiKey: CLJDCDQIFYBNKL-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-((tetrahydro-4H-pyran-4-yloxy)carbonyl)-L-leucine N-hydroxysuccinimide ester 在 戴斯-马丁氧化剂 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 ((1S)-1-((((1S)-1-benzyl-2,3-dioxo-3-(ethylamino)propyl)amino)carbonyl)-3-methylbutyl)carbamic acid tetrahydro-4H-pyran-4-yl ester
  参考文献：
  名称：

  Exploration of orally available calpain inhibitors: Peptidyl α-ketoamides containing an amphiphile at P3 site

  摘要：

  A novel series of dipeptidyl alpha-ketoamide derivatives with amphiphile was designed and synthesized as water-soluble calpain inhibitors. The introduction of amphiphiles at the P3 site increased water solubility without loss of membrane permeability and provided the oral available inhibitors. Extension of the ethylene glycol chain at the P3 site led to an improvement in persistence of plasma levels. In particular, introduction of a combination of a diethylene glycol methyl ether moiety at the P3 site, a phenylalanine residue at the P1 site and a cyclopropyl moiety at the P' site was the most effective modification for an increase in plasma drug exposure. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.04.059
• 作为产物：
  描述：

  N-((tetrahydro-4H-pyran-4-yloxy)carbonyl)-L-leucine ethyl ester 在 sodium hydroxide 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 生成 N-((tetrahydro-4H-pyran-4-yloxy)carbonyl)-L-leucine N-hydroxysuccinimide ester
  参考文献：
  名称：

  Exploration of orally available calpain inhibitors: Peptidyl α-ketoamides containing an amphiphile at P3 site

  摘要：

  A novel series of dipeptidyl alpha-ketoamide derivatives with amphiphile was designed and synthesized as water-soluble calpain inhibitors. The introduction of amphiphiles at the P3 site increased water solubility without loss of membrane permeability and provided the oral available inhibitors. Extension of the ethylene glycol chain at the P3 site led to an improvement in persistence of plasma levels. In particular, introduction of a combination of a diethylene glycol methyl ether moiety at the P3 site, a phenylalanine residue at the P1 site and a cyclopropyl moiety at the P' site was the most effective modification for an increase in plasma drug exposure. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.04.059

文献信息

• Alpha-ketoamide derivative, and production method and use thereof
  申请人：Shirasaki Yoshihisa

  公开号：US20070004643A1

  公开（公告）日：2007-01-04

  The present invention provides a compound represented by the formula (I): (wherein R 1 is a lower alkyl substituted by a lower alkoxy or a heterocyclic group, or a heterocyclic group; R 2 is a lower alkyl optionally substituted by a phenyl; and R 3 is a lower alkyl optionally substituted by a halogen, a lower alkoxy or a phenyl, or a fused polycyclic hydrocarbon group), which is well absorbed orally, exhibits durability of good blood level and has potent calpain inhibitory activity.

  本发明提供了一种化合物，其化学式表示为(I):(其中，R1是一个低烷基，该低烷基被低烷氧基或杂环基取代，或者是一个杂环基；R2是一个低烷基，可选地被苯基取代；R3是一个低烷基，可选地被卤素、低烷氧基或苯基取代，或者是一个融合的多环碳氢基)，该化合物口服吸收良好，血液水平持久，具有强大的钙蛋白酶抑制活性。
• COMPOSITION FOR TREATMENT AND/OR PREVENTION OF PERIPHERAL NERVE DISORDER
  申请人：Osaka City University

  公开号：EP3466421A1

  公开（公告）日：2019-04-10

  The present invention provides a means for treating and/or preventing peripheral nerve disorder by facilitating regeneration of peripheral nerves. Specifically, the present invention provides a composition for treating and/or preventing peripheral nerve disorder comprising a compound represented by the general formula (I) : wherein R1 is lower alkyl substituted with lower alkoxy, lower alkyl substituted with a heterocyclic group, a heterocyclic group, or a group represented by the formula (IIa): wherein R4 is lower alkyl, R5 is lower alkylene, and m is an integer of 1 to 6; R2 is lower alkyl optionally substituted with phenyl; and R3 is lower alkyl optionally substituted with halogen, lower alkoxy, or phenyl; condensed polycyclic hydrocarbon; or hydrogen.

  本发明提供了一种通过促进周围神经再生来治疗和/或预防周围神经紊乱的方法。具体而言，本发明提供了一种用于治疗和/或预防周围神经紊乱的组合物，该组合物由通式（I）所代表的化合物组成： 其中 R1 是被低级烷氧基取代的低级烷基、被杂环基取代的低级烷基、杂环基或式 (IIa) 所代表的基团： 其中 R4 是低级烷基，R5 是低级亚烷基，m 是 1 至 6 的整数； R2 是可选被苯基取代的低级烷基；和 R3 是可选被卤素、低级烷氧基或苯基取代的低级烷基；缩合多环烃；或氢。
• LISSENCEPHALY THERAPEUTIC AGENT
  申请人：Osaka City University

  公开号：EP2647386B1

  公开（公告）日：2018-09-05
• ALPHA-KETOAMIDE DERIVATIVE, AND PRODUCTION METHOD AND USE THEREOF
  申请人：Senju Pharmaceutical Co., Ltd.

  公开号：EP1692098B1

  公开（公告）日：2009-10-28
• US7491705B2
  申请人：——

  公开号：US7491705B2

  公开（公告）日：2009-02-17