tert-butyl N-[(4'-hydroxy-1,1'-biphenyl-4-yl)sulfonyl]-D-valinate | 854372-00-2

• 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: tert-butyl N-[(4'-hydroxy-1,1'-biphenyl-4-yl)sulfonyl]-D-valinate
• 英文别名: (R)-2-(4'-hydroxy-biphenyl-4-sulfonylamino)-3-methyl-butyric acid tert-butyl ester；tert-butyl (2R)-2-[[4-(4-hydroxyphenyl)phenyl]sulfonylamino]-3-methylbutanoate
• CAS: 854372-00-2
• 化学式: C₂₁H₂₇NO₅S
• 分子量: 405.515
• InChiKey: ACSCDVOXADKAOE-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(4'-hydroxy-1,1'-biphenyl-4-yl)sulfonyl]-D-valinate 在 N,N'-二环己基碳二亚胺 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以30.5%的产率得到benzofuran-2-carboxylic acid 4'-(1-tert-butoxycarbonyl-2-methylpropylsulfamoyl)biphenyl-4-yl ester
  参考文献：
  名称：

  Biaryl sulfonamides and methods for using same

  摘要：

  本发明涉及联苯磺酰胺及其用途，例如作为金属蛋白酶抑制剂。

  公开号：

  US20050130973A1
• 作为产物：
  描述：

  D-缬氨酸叔丁基盐酸盐 在 四(三苯基膦)钯 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 15.0h， 生成 tert-butyl N-[(4'-hydroxy-1,1'-biphenyl-4-yl)sulfonyl]-D-valinate
  参考文献：
  名称：

  Synthesis and biological evaluation of biphenylsulfonamide carboxylate aggrecanase-1 inhibitors

  摘要：

  Aggrecanases are recently discovered enzymes that cleave aggrecan, a key component of cartilage. Aggrecanase inhibitors may provide a unique means to halt the progression of cartilage destruction in osteoarthritis. The synthesis and evaluation of biphenylsulfonamidocarboxylic acid inhibitors of aggrecanase-1 are reported. Compound 24 demonstrated 89% inhibition of proteoglycan degradation at 10 mu g/mL and has an oral bioavailability in rat of 35%. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.10.001

文献信息

• Biaryl Sulfonamides and Methods for Using Same
  申请人：Xiang Shaoyun Jason

  公开号：US20070225327A1

  公开（公告）日：2007-09-27

  The present invention relates to biaryl sulfonamides and their use as, for example, metalloproteinase inhibitors.

  本发明涉及联苯磺酰胺及其用途，例如作为金属蛋白酶抑制剂。
• 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。
• Potent, selective, and orally bioavailable matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis
  作者：Yonghan Hu、Jason S. Xiang、Martin J. DiGrandi、Xuemei Du、Manus Ipek、Leif M. Laakso、Jianchang Li、Wei Li、Thomas S. Rush、Jean Schmid、Jerauld S. Skotnicki、Steve Tam、Jennifer R. Thomason、Qin Wang、Jeremy I. Levin

  DOI：10.1016/j.bmc.2005.07.076

  日期：2005.12

  Modification of alpha-biphenylsulfonamidocarboxylic acids led to potent and selective MMP-13 inhibitors. Compound 16 showed 100% oral bioavailability in rats and demonstrated > 50% inhibition of bovine cartilage degradation at 10 ng/mL. (c) 2005 Elsevier Ltd. All rights reserved.
• Continued exploration of biphenylsulfonamide scaffold as a platform for aggrecanase-1 inhibition
  作者：Yonghan Hu、Li Xing、Jennifer R. Thomason、Jason Xiang、Manus Ipek、Satenig Guler、Huanqiu Li、Joshua Sabatini、Priya Chockalingam、Erica Reifenberg、Richard Sheldon、Elisabeth A. Morris、Katy E. Georgiadis、Steve Tam

  DOI：10.1016/j.bmcl.2011.09.036

  日期：2011.11

  Design, synthesis and structure-activity relationship of a series of biphenylsulfonamido-3-methylbutanoic acid based aggrecanase-1 inhibitors are described. In addition to robust aggrecanase-1 inhibition, these compounds also exhibit potent MMP-13 activity. In cell-based cartilage explants assay compound 48 produced 87% inhibition of proteoglycan degradation at 10 mu g/mL. Good pharmacokinetic properties were demonstrated by 46 with a half-life of 6 h and bioavailability of 23%. (C) 2011 Elsevier Ltd. All rights reserved.
• US7268135B2
  申请人：——

  公开号：US7268135B2

  公开（公告）日：2007-09-11