N-({4'-[(4-Isobutyrylphenoxy)methyl]biphenyl-4-Yl}sulfonyl)-D-Valine | 925430-98-4

• 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'-[(4-Isobutyrylphenoxy)methyl]biphenyl-4-Yl}sulfonyl)-D-Valine
• 英文别名: (2R)-3-methyl-2-[[4-[4-[[4-(2-methylpropanoyl)phenoxy]methyl]phenyl]phenyl]sulfonylamino]butanoic acid
• CAS: 925430-98-4
• 化学式: C₂₈H₃₁NO₆S
• 分子量: 509.623
• InChiKey: JGTIIKHYSZFICL-AREMUKBSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-({4'-[(4-Isobutyrylphenoxy)methyl]biphenyl-4-Yl}sulfonyl)-D-Valine
  参考文献：
  名称：

  Synthesis and biological evaluation of ((4-keto)-phenoxy)methyl biphenyl-4-sulfonamides: A class of potent aggrecanase-1 inhibitors

  摘要：

  The prevention of aggrecan (a key component of cartilage) cleavage via the inhibition of aggrecanase-1 may provide a unique opportunity to stop the progression of cartilage degradation in osteoarthritis. The evaluation of a series of biphenylsulfonamides resulted in the identification of the ((4-keto)-phenoxy) methyl biphenyl-4-sulfonamides analogs (19-21 and 24) with improved Agg-1 inhibition and MMP-2, MMP-13 activity. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.056

文献信息

• METHOD FOR TREATING ADAMTS-5-ASSOCIATED DISEASE
  申请人：Morris Elisabeth A.

  公开号：US20080311113A1

  公开（公告）日：2008-12-18

  The present invention relates to methods of treating ADAMTS-5-associated diseases and particularly osteoarthritis comprising administering an agent capable of modulating ADMATS-5 activity to a subject afflicted with the disease. The agent is preferably a biaryl sulfonamide compound. The invention is based, in part, on the discovery that transgenic animals that do not express functional ADAMTS-5 show a reduction in the degree of osteoarthritis after the induction of osteoarthritis as compared to WT animals. Furthermore, the ADAMTS-5 transgenic animals have reduced aggrecanase activity in articular tissue as compared to WT animals. These animals are good models for ADAMTS-5-associated diseases, and for screening of drugs useful in the treatment and/or prevention of these diseases. There are no other animal models in which the deletion of the activity of a single gene is capable of abrogating the course of osteoarthritis. Accordingly, these animals also show that osteoarthritis can be prevented and/or treated by administering to a subject an ADAMTS-5 inhibitory agent and particularly an agent capable of inhibiting the aggrecanase activity of ADAMTS-5.

  本发明涉及治疗ADAMTS-5相关疾病，尤其是骨关节炎的方法，包括向患有该疾病的受试者施用能够调节ADMATS-5活性的药剂。该药剂优选为双芳基磺酰胺化合物。该发明部分基于这样的发现，即不表达功能性ADAMTS-5的转基因动物在诱导骨关节炎后与WT动物相比，显示出骨关节炎程度的降低。此外，ADAMTS-5转基因动物在关节组织中的聚集素酶活性相对于WT动物也有所降低。这些动物是ADAMTS-5相关疾病的良好模型，可用于筛选对治疗和/或预防这些疾病有用的药物。没有其他动物模型能够通过删除单个基因的活性来消除骨关节炎的进程。因此，这些动物还表明，通过向受试者施用ADAMTS-5抑制剂，尤其是能够抑制ADAMTS-5聚集素酶活性的药剂，可以预防和/或治疗骨关节炎。
• US7390833B2
  申请人：——

  公开号：US7390833B2

  公开（公告）日：2008-06-24
• Synthesis and biological evaluation of ((4-keto)-phenoxy)methyl biphenyl-4-sulfonamides: A class of potent aggrecanase-1 inhibitors
  作者：Darrin W. Hopper、Matthew D. Vera、David How、Joshua Sabatini、Jason S. Xiang、Manus Ipek、Jennifer Thomason、Yonghan Hu、Eric Feyfant、Qin Wang、Katy E. Georgiadis、Erica Reifenberg、Richard T. Sheldon、Cristin C. Keohan、Manas K. Majumdar、Elisabeth A. Morris、Jerauld Skotnicki、Phaik-Eng Sum

  DOI：10.1016/j.bmcl.2009.03.056

  日期：2009.5

  The prevention of aggrecan (a key component of cartilage) cleavage via the inhibition of aggrecanase-1 may provide a unique opportunity to stop the progression of cartilage degradation in osteoarthritis. The evaluation of a series of biphenylsulfonamides resulted in the identification of the ((4-keto)-phenoxy) methyl biphenyl-4-sulfonamides analogs (19-21 and 24) with improved Agg-1 inhibition and MMP-2, MMP-13 activity. (c) 2009 Elsevier Ltd. All rights reserved.