(R)-4-acetamido-N-hydroxy-2-(N-isopropoxy-4′-methoxybiphenyl-4-ylsulfonamido)butanamide | 1061742-52-6

• 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: (R)-4-acetamido-N-hydroxy-2-(N-isopropoxy-4′-methoxybiphenyl-4-ylsulfonamido)butanamide
• 英文别名: (R)-4-acetamido-N-hydroxy-2-(N-isopropoxy-4'-methoxybiphenyl-4-ylsulfonamido)butanamide；(2R)-4-acetamido-N-hydroxy-2-[[4-(4-methoxyphenyl)phenyl]sulfonyl-propan-2-yloxyamino]butanamide
• CAS: 1061742-52-6
• 化学式: C₂₂H₂₉N₃O₇S
• 分子量: 479.554
• InChiKey: UJKKQEHHLXCTJE-OAQYLSRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  143
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (R)-4-tert-butoxy-3-(N-isopropoxy-4'-methoxybiphenyl-4-ylsulfonamido)-4-oxobutan-1-aminium acetate 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 (R)-4-acetamido-N-hydroxy-2-(N-isopropoxy-4′-methoxybiphenyl-4-ylsulfonamido)butanamide
  参考文献：
  名称：

  N-O-Isopropyl Sulfonamido-Based Hydroxamates as Matrix Metalloproteinase Inhibitors: Hit Selection and in Vivo Antiangiogenic Activity

  摘要：

  Matrix metalloproteinases (MMPs) have been shown to be involved in tumor-induced angiogenesis. In particular, MMP-2, MMP-9, and MMP-14 have been reported to be crucial for tumor angiogenesis and the formation of metastasis, thus becoming attractive targets in cancer therapy. Here, we report our optimization effort to identify novel N-isopropoxy-arylsulfonamide hydroxamates with improved inhibitory activity toward MMP-2, MMP-9, and MMP-14 with respect to the previously discovered compound 1. A new series of hydroxamates was designed, synthesized, and tested for their antiangiogenic activity using in vitro assays with human umbilical vein endothelial cells (HUVECs). A nanomolar MMP-2, MMP-9, and MMP-14 inhibitor was identified, compound 3, able to potently inhibit angiogenesis in vitro and also in vivo in the matrigel sponge assay in mice. Finally, X-ray crystallographic and docking studies were conducted for compound 3 in order to investigate its binding mode to MMP-9 and MMP-14.

  DOI：

  10.1021/acs.jmedchem.5b00367

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。
• Compounds having aryl-sulphonamidic structure useful as metalloproteases inhibitors
  申请人：Bracco S.P.A.

  公开号：EP1972617A1

  公开（公告）日：2008-09-24

  The invention relates to aryl-sulphonamido compounds endowed with inhibitory activity against metallo proteases MMP, having formula (I) below wherein R, R1, R2, R3, R4, R5, n and m 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.

  本发明涉及具有对金属蛋白酶MMP具有抑制活性的芳基磺胺基化合物，其具有以下式（I）其中R、R1、R2、R3、R4、R5、n和m具有规范中报告的含义；本发明还涉及它们的制备方法，包括它们的制药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。
• Diagnostic Agents Selective Against Metalloproteases
  申请人：Bracco Imaging S.p.A

  公开号：EP2147684A1

  公开（公告）日：2010-01-27

  The invention relates to aryl-sulphonamido compounds endowed with affinity against metallo proteases MMP, having formula (I) below wherein R, R1, R2, R3, G and n have the meanings reported in the specification, properly labelled with diagnostic imaging moieties or even radiotherapeutic moieties. The invention also refers to the process for their preparation, to pharmaceutical compositions comprising them and to their use as diagnostic imaging agents or radiotherapeutic agents.

  本发明涉及具有亲和力对金属蛋白酶MMP的芳基磺酰胺化合物，其化学式如下（I），其中R，R1，R2，R3，G和n在规范中有所说明，适当地标记有诊断成像或放射治疗成分。本发明还涉及它们的制备过程、包含它们的药物组成物以及它们作为诊断成像剂或放射治疗剂的用途。
• DIAGNOSTIC AGENTS SELECTIVE AGAINST METALLOPROTEASES
  申请人：Bracco Imaging S.p.A.

  公开号：EP2320954B1

  公开（公告）日：2019-09-04
• Compounds Having Aryl-Sulphonamidic Structure Useful As Metalloproteases Inhibitors
  申请人：Balsamo Aldo

  公开号：US20100087505A1

  公开（公告）日：2010-04-08

  The invention relates to aryl-sulphonamido compounds endowed with inhibitory activity against metallo proteases MMP, having formula (I) below wherein R, R 1 , R 2 , R 3 , R 4 , R 5 , n and m 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.