cis-3-t-butoxycarbonylthio-4-acetylthio-N-Boc-pyrrolidine

• 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: cis-3-t-butoxycarbonylthio-4-acetylthio-N-Boc-pyrrolidine
• 英文别名: tert-butyl (3S,4R)-3-acetylsulfanyl-4-[(2-methylpropan-2-yl)oxycarbonylsulfanyl]pyrrolidine-1-carboxylate
• 化学式: C₁₆H₂₇NO₅S₂
• 分子量: 377.526
• InChiKey: JOQDNBUZNAIGSU-NWDGAFQWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  124
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  cis-3-t-butoxycarbonylthio-4-acetylthio-N-Boc-pyrrolidine 在 盐酸 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 O-(tert-butyl) S-(1-(6-(1,3-dioxoisoindolin-2-yl)hexanoyl)-4-(((R)-4-methyl-1-(((S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxopentan-2-yl)thio)pyrrolidin-3-yl) carbonothioate
  参考文献：
  名称：

  Matrix Metalloproteinase Inhibitors Based on the 3-Mercaptopyrrolidine Core

  摘要：

  New series of pyrrolidine mercaptosulfide, 2-mercaptocyclopentane arylsulfonamide, and 3-mercapto-4-arylsulfonamidopyrrolidine matrix metalloproteinase inhibitors (MMPIs) were designed, synthesized, and evaluated. Exhibiting unique properties over other MMPIs (e.g., hydroxamates), these newly reported compounds are capable of modulating activities of several MMPs in the low nanomolar range, including MMP-2 (similar to 2 to 50 nM), MMP-13 (similar to 2 to 50 nM), and MMP-14 (similar to 4 to 60 nM). Additionally these compounds are selective to intermediate- and deep-pocket MMPs but not shallow-pocketed MMPs (e.g., MMP-1, similar to 850 to >50 000 nM; MMP-7, similar to 4000 to >25 000 nM). Our previous work with the mercaptosulfide functionality attached to both cyclopentane and pyrrolidine frameworks demonstrated that the cis-(3S,4R)-stereochemistry was optimal for all of the MMPs tested. However, in our newest compounds an interesting shift of preference to the trans form of the mercaptosulfonamides was observed with increased oxidative stability and biological compatibility. We also report several kinetic and biological characteristics showing that these compounds may be used to probe the mechanistic activities of MMPs in disease.

  DOI：

  10.1021/jm400529f
• 作为产物：
  描述：

  N-Boc-3-吡咯啉 在 aluminum oxide 、 sodium ethanolate 、 间氯过氧苯甲酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 生成 cis-3-t-butoxycarbonylthio-4-acetylthio-N-Boc-pyrrolidine
  参考文献：
  名称：

  Matrix Metalloproteinase Inhibitors Based on the 3-Mercaptopyrrolidine Core

  摘要：

  New series of pyrrolidine mercaptosulfide, 2-mercaptocyclopentane arylsulfonamide, and 3-mercapto-4-arylsulfonamidopyrrolidine matrix metalloproteinase inhibitors (MMPIs) were designed, synthesized, and evaluated. Exhibiting unique properties over other MMPIs (e.g., hydroxamates), these newly reported compounds are capable of modulating activities of several MMPs in the low nanomolar range, including MMP-2 (similar to 2 to 50 nM), MMP-13 (similar to 2 to 50 nM), and MMP-14 (similar to 4 to 60 nM). Additionally these compounds are selective to intermediate- and deep-pocket MMPs but not shallow-pocketed MMPs (e.g., MMP-1, similar to 850 to >50 000 nM; MMP-7, similar to 4000 to >25 000 nM). Our previous work with the mercaptosulfide functionality attached to both cyclopentane and pyrrolidine frameworks demonstrated that the cis-(3S,4R)-stereochemistry was optimal for all of the MMPs tested. However, in our newest compounds an interesting shift of preference to the trans form of the mercaptosulfonamides was observed with increased oxidative stability and biological compatibility. We also report several kinetic and biological characteristics showing that these compounds may be used to probe the mechanistic activities of MMPs in disease.

  DOI：

  10.1021/jm400529f

文献信息

• [EN] SUBSTITUTED HETEROCYCLIC MERCAPTOSULFIDE INHIBITORS<br/>[FR] INHIBITEURS DE MERCAPTOSULFURE HÉTÉROCYCLIQUE SUBSTITUÉ
  申请人：UNIV FLORIDA STATE RES FOUND

  公开号：WO2005032541A1

  公开（公告）日：2005-04-14

  Novel substituted heterocyclic mercaptosulfide compounds, precursors, and derivatives, the methods for the preparation, and pharmaceutical compositions of these compounds are described in this invention. These compounds are developed and tested to be potent and relatively selective inhibitors of matrix metalloproteinases (MMPs), e.g. membrane type 1 MMP, gelatinase B, gelatinase A, collagenases, matrilysins, metalloelastase, and stromelysin-1. These inhibitors will be used for the control of physiological and pathological processes in which metalloproteases play a significant role. These inhibitors can be used for human beings, animals, and other organisms.

  本发明描述了一种新型替代杂环巯基硫醚化合物、前体和衍生物的方法以及这些化合物的制备方法和制药组合物。这些化合物经过开发和测试，被证明是强效且相对选择性的基质金属蛋白酶（MMPs）抑制剂，例如膜型1 MMP、明胶酶B、明胶酶A、胶原酶、基质蛋白酶、金属弹性蛋白酶和基质金属蛋白酶1。这些抑制剂将用于控制生理和病理过程，其中金属蛋白酶发挥重要作用。这些抑制剂可用于人类、动物和其他生物。
• A practical synthesis of differentially-protected cis-1,2-cyclopentanedithiols and cis-3,4-pyrrolidinedithiols
  作者：Yonghao Jin、Mohammad A Ghaffari、Martin A Schwartz

  DOI：10.1016/s0040-4039(02)01750-1

  日期：2002.10

  A practical method for the synthesis of cis-1,2-cyclopentanedithiols and cis-3,4-pyrrolidinedithiols with differentially protected sulfurs, needed for the design of new metal-chelating ligands, has been developed. (C) 2002 Published by Elsevier Science Ltd.
• Matrix Metalloproteinase Inhibitors Based on the 3-Mercaptopyrrolidine Core
  作者：Yonghao Jin、Mark D. Roycik、Dale B. Bosco、Qiang Cao、Manuel H. Constantino、Martin A. Schwartz、Qing-Xiang Amy Sang

  DOI：10.1021/jm400529f

  日期：2013.6.13

  New series of pyrrolidine mercaptosulfide, 2-mercaptocyclopentane arylsulfonamide, and 3-mercapto-4-arylsulfonamidopyrrolidine matrix metalloproteinase inhibitors (MMPIs) were designed, synthesized, and evaluated. Exhibiting unique properties over other MMPIs (e.g., hydroxamates), these newly reported compounds are capable of modulating activities of several MMPs in the low nanomolar range, including MMP-2 (similar to 2 to 50 nM), MMP-13 (similar to 2 to 50 nM), and MMP-14 (similar to 4 to 60 nM). Additionally these compounds are selective to intermediate- and deep-pocket MMPs but not shallow-pocketed MMPs (e.g., MMP-1, similar to 850 to >50 000 nM; MMP-7, similar to 4000 to >25 000 nM). Our previous work with the mercaptosulfide functionality attached to both cyclopentane and pyrrolidine frameworks demonstrated that the cis-(3S,4R)-stereochemistry was optimal for all of the MMPs tested. However, in our newest compounds an interesting shift of preference to the trans form of the mercaptosulfonamides was observed with increased oxidative stability and biological compatibility. We also report several kinetic and biological characteristics showing that these compounds may be used to probe the mechanistic activities of MMPs in disease.