4-[3-(3-Chlorocarbonyl-propylcarbamoyl)-benzoylamino]-butyryl chloride | 853755-36-9

• 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: 4-[3-(3-Chlorocarbonyl-propylcarbamoyl)-benzoylamino]-butyryl chloride
• 英文别名: 4-[[3-[(4-Chloro-4-oxobutyl)carbamoyl]benzoyl]amino]butanoyl chloride
• CAS: 853755-36-9
• 化学式: C₁₆H₁₈Cl₂N₂O₄
• 分子量: 373.236
• InChiKey: DOOHDHZFSLFRKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  92.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[3-(3-Chlorocarbonyl-propylcarbamoyl)-benzoylamino]-butyryl chloride 在 N-甲基吗啉 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 N,N'-Bis(4-{[(3r)-3-[(Biphenyl-4-Ylsulfonyl)(Propan-2-Yloxy)amino]-4-(Hydroxyamino)-4-Oxobutyl]amino}-4-Oxobutyl)benzene-1,3-Dicarboxamide
  参考文献：
  名称：

  A new development of matrix metalloproteinase inhibitors: twin hydroxamic acids as potent inhibitors of MMPs

  摘要：

  Starting from the observation that the CbzNH(CH2)(2) side chain of the potent MMP-2/MMP-14 inhibitor, benzyl-(3R)-4-(hydroxyamino)-3-[isopropoxy(1,1'-biphenyl-4yl-sulfonyl)amino]-4-oxobutylcarbamate, (R)-1 lies in a hydrophobic region (S1) exposed to the solvent of the protease active site, we hypothesized that an aminoethylcarboxamido chain structurally related to that of (R)-1 might be an useful tool to bind another linker stretching out from the protein. This would be able to interact either with a enzyme region adjacent to the active site, or with other molecules of matrix metalloproteinases (MMPs), or other proteins of the extracellular matrix (ECM) that may be involved in the enzyme activation. On these basis we describe new dimeric compounds of type 2, twin hydroxamic acids, obtained by the joint of two drug entities of (R)-1 linked in PI by extendable semirigid linkers. Type 2 compounds are potentially able to undergo more complex inhibitor enzyme interactions than those occurring with monomeric compounds of type 1, thus influencing positively the potency, selectivity and/or cytotoxicity of the new compounds. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.03.002
• 作为产物：
  描述：

  4-[[3-(3-Carboxypropylcarbamoyl)benzoyl]amino]butanoic acid 在 草酰氯 作用下， 以 吡啶 、 甲苯 为溶剂， 生成 4-[3-(3-Chlorocarbonyl-propylcarbamoyl)-benzoylamino]-butyryl chloride
  参考文献：
  名称：

  A new development of matrix metalloproteinase inhibitors: twin hydroxamic acids as potent inhibitors of MMPs

  摘要：

  Starting from the observation that the CbzNH(CH2)(2) side chain of the potent MMP-2/MMP-14 inhibitor, benzyl-(3R)-4-(hydroxyamino)-3-[isopropoxy(1,1'-biphenyl-4yl-sulfonyl)amino]-4-oxobutylcarbamate, (R)-1 lies in a hydrophobic region (S1) exposed to the solvent of the protease active site, we hypothesized that an aminoethylcarboxamido chain structurally related to that of (R)-1 might be an useful tool to bind another linker stretching out from the protein. This would be able to interact either with a enzyme region adjacent to the active site, or with other molecules of matrix metalloproteinases (MMPs), or other proteins of the extracellular matrix (ECM) that may be involved in the enzyme activation. On these basis we describe new dimeric compounds of type 2, twin hydroxamic acids, obtained by the joint of two drug entities of (R)-1 linked in PI by extendable semirigid linkers. Type 2 compounds are potentially able to undergo more complex inhibitor enzyme interactions than those occurring with monomeric compounds of type 1, thus influencing positively the potency, selectivity and/or cytotoxicity of the new compounds. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.03.002

文献信息

• ARYL-SULPHONAMIDIC DIMERS AS METALLOPROTEASES INHIBITORS
  申请人：Bracco Imaging S.p.A

  公开号：EP2149568A1

  公开（公告）日：2010-02-03

  The invention relates to dimeric aryl-sulphonamido compounds endowed with inhibitory activity against metalloproteases MMP, having formula (I) below          (M)-L-(M')     (I) wherein M and M', the same or different from each other, represent the residues of the mctalloprotcascs inhibitors of formula (II) wherein R, R1, R2, R3, G and n have the meanings reported in the specification; the invention also refers to the process for their preparation, to pharmaceutical compositions comprising them and to their use as therapeutic agents, particularly in the treatment of degenerative disorders.

  该发明涉及具有对金属蛋白酶MMP具有抑制活性的二聚芳基磺胺基化合物，其具有以下式(I)：(M)-L-(M')，其中M和M'，相同或不同，代表具有以下式(II)金属蛋白酶抑制剂的残基，其中R、R1、R2、R3、G和n在说明书中有所述；该发明还涉及其制备方法，包括它们的药物组合物以及它们作为治疗剂的用途，特别是在治疗退行性疾病方面。
• Design, synthesis and biological evaluation of bifunctional inhibitors of membrane type 1 matrix metalloproteinase (MT1-MMP)
  作者：Doretta Cuffaro、Elisa Nuti、Valentina Gifford、Noriko Ito、Caterina Camodeca、Tiziano Tuccinardi、Susanna Nencetti、Elisabetta Orlandini、Yoshifumi Itoh、Armando Rossello

  DOI：10.1016/j.bmc.2018.11.041

  日期：2019.1

  cell surface, herein we propose that the use of bifunctional inhibitors of this enzyme could represent an innovative approach to efficiently reduce tumor growth. A small series of symmetrical dimers derived from previously described monomeric arylsulfonamide hydroxamates was synthesized and tested in vitro on isolated MMPs. A nanomolar MT1-MMP inhibitor, compound 6, was identified and then submitted

  胶原蛋白降解和proMMP-2激活是MT1-MMP促进癌细胞侵袭的主要功能。由于这两个过程都需要细胞表面上的 MT1-MMP 同二聚化，因此我们提出使用该酶的双功能抑制剂可以代表一种有效减少肿瘤生长的创新方法。合成了源自先前描述的单体芳基磺酰胺异羟肟酸盐的一小组对称二聚体，并在分离的 MMP 上进行了体外测试。鉴定出一种纳摩尔 MT1-MMP 抑制剂（化合物6），然后对 HT1080 纤维肉瘤细胞进行基于细胞的测定。二聚体6以剂量依赖性方式减少 MT1-MMP 依赖性 proMMP-2 激活、胶原蛋白降解和胶原蛋白侵袭，甚至与其单体类似物相比，效果更好4。这项初步研究表明二聚体 MT1-MMP 抑制剂可能会被进一步开发和利用作为减少癌细胞侵袭的替代工具。