N-((4-fluorophenyl)sulfonyl)-L-valine N-hydroxysuccinimide ester | 190275-58-2

• 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-((4-fluorophenyl)sulfonyl)-L-valine N-hydroxysuccinimide ester
• 英文别名: N-(4-fluorophenylsulfonyl)-L-valine N-hydroxysuccinimide ester；(2,5-dioxopyrrolidin-1-yl) (2S)-2-[(4-fluorophenyl)sulfonylamino]-3-methylbutanoate
• CAS: 190275-58-2
• 化学式: C₁₅H₁₇FN₂O₆S
• 分子量: 372.374
• InChiKey: NHXDOOUTCARAMF-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-((4-fluorophenyl)sulfonyl)-L-valine N-hydroxysuccinimide ester 在 pyridine-SO3 complex 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 反应 18.5h， 生成 钙蛋白酶抑制剂VI
  参考文献：
  名称：

  Exploration of cornea permeable calpain inhibitors as anticataract agents

  摘要：

  To explore cornea permeable calpain inhibitors, four compounds displaying different characteristics were designed and synthesized based on the known potent calpain inhibitor, peptidyl aldehyde SJA6017. Two approaches were adopted; an improvement in the physicochemical properties, and conversion of the active aldehyde. The water-soluble peptidyl aldehyde 1 containing a pyridine ring at the P3 site showed a modest inhibition against calpains and an improvement of corneal permeability in comparison with SJA6017. Replacement of the aldehyde of SJA6017 by an alpha-ketoamide provided compound 2 that was approximately equipotent with SJA6017, but it was extremely water-in soluble. However, compound 3, in which the aldehyde was converted into a cyclic hemiacetal, proved to be a less potent calpain inhibitor than SJA6017, but demonstrated excellent transcorneal permeability. Further modification generating the cyclic hermacetal 4 containing a thiourea linker between the P3 and P2 sites exhibited potent inhibitory activities, high cornea permeability and excellent efficacy in the rat lens culture cataract model. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00612-0
• 作为产物：
  描述：

  4-氟苯磺酰氯 在 sodium hydroxide 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 N-((4-fluorophenyl)sulfonyl)-L-valine N-hydroxysuccinimide ester
  参考文献：
  名称：

  Structure−Activity Relationship Study and Drug Profile of N-(4-Fluorophenylsulfonyl)-l-valyl-l-leucinal (SJA6017) as a Potent Calpain Inhibitor

  摘要：

  Novel N-arylsulfonyldipeptidyl aldehyde derivatives were prepared by DMSO oxidation from the corresponding dipeptide alcohol, and their potencies as calpain inhibitors were evaluated in vitro. Among them, N-(4-fluorophenylsulfonyl)-L-valyl-L-leucinal (8, SJA6017) potently inhibited calpains. 8 also inhibited cathepsin B and L but did not inhibit other cysteine proteases (interleukin 1beta-converting enzyme), serine proteases (trypsin, chymotrypsin, thrombin, factor VIIa, factor Xa), or proteasome. Preliminary cytotoxicity studies of 8 exhibited a relatively safe profile.

  DOI：

  10.1021/jm0201924

文献信息

• Novel alpha-ketomide derivative and use thereof
  申请人：Nakamura Masayuki

  公开号：US20050165113A1

  公开（公告）日：2005-07-28

  The present invention provides a compound represented by the formula (I): wherein R 1 , R 2 and R 3 each represents a lower alkyl group.

  本发明提供了一种由公式（I）表示的化合物：其中R1、R2和R3各代表低碳基团。
• NOVEL ALPHA-KETOAMIDE DERIVATIVE AND USE THEREOF
  申请人：Senju Pharmaceutical Co., Ltd.

  公开号：EP1557407A1

  公开（公告）日：2005-07-27

  The present invention provides a compound represented by the formula (I): wherein R1, R2 and R3 each represents a lower alkyl group.

  本发明提供了一种由式（I）表示的化合物： 其中 R1、R2 和 R3 各代表一个低级烷基。
• NOVEL ALPHA-KETOAMIDE DERIVATIVES AND USE THEREOF
  申请人：Senju Pharmaceutical Co., Ltd.

  公开号：EP1557407B1

  公开（公告）日：2009-11-11
• Exploration of Orally Available Calpain Inhibitors 2:  Peptidyl Hemiacetal Derivatives
  作者：Yoshihisa Shirasaki、Masayuki Nakamura、Masazumi Yamaguchi、Hiroyuki Miyashita、Osamu Sakai、Jun Inoue

  DOI：10.1021/jm060157n

  日期：2006.6.1

  We previously reported a potent calpain inhibitor 1 ( SJA6017, N-( 4-fluorophenyl)-L-valyl-L-leucinal), which displayed relatively low oral bioavailability ( BA). Replacing the metabolically labile aldehyde moiety of 1 with more chemically stable warheads, such as a cyclic hemiacetal, hydrazone, and alpha-ketoamide, provided the inhibitors with improved in vitro metabolic stability. Cyclic hemiacetal 2 was the most stable of these compounds. The optimization of 2 led to hemiacetal 8 ( SNJ-1715) which exhibited high potency, good aqueous solubility, excellent oral BA, and prolonged plasma half-life in rats. Furthermore, 8 showed neuroprotective efficacy via oral administration in a rat retinal ischemia model.
• Angiogenesis inhibitor
  申请人：Senju Pharmaceutical Co., Ltd.

  公开号：EP0771565B1

  公开（公告）日：2003-01-02