3-methyl-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenoxymethyl]benzofuran | 854371-73-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 3-methyl-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenoxymethyl]benzofuran
• 英文别名: 3-Methyl-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxymethyl]-benzofuran；4,4,5,5-tetramethyl-2-[4-[(3-methyl-1-benzofuran-2-yl)methoxy]phenyl]-1,3,2-dioxaborolane
• CAS: 854371-73-6
• 化学式: C₂₂H₂₅BO₄
• 分子量: 364.249
• InChiKey: NALDHPXYHCNPAB-UHFFFAOYSA-N

物化性质

• 沸点：
  494.9±40.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.62
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  40.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-methyl-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenoxymethyl]benzofuran 在 四(三苯基膦)钯 lithium hydroxide 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 水 为溶剂， 反应 20.0h， 生成 D-3-methyl-2-[4'-(3-methyl-benzofuran-2-ylmethoxy)-biphenyl-4-sulfonylamino]-butyric acid
  参考文献：
  名称：

  Potent, selective, and orally bioavailable matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2005.07.076
• 作为产物：
  描述：

  2-Chloromethyl-3-methyl-benzofuran 、 4-羟基苯硼酸频哪醇酯 以to give 3-methyl-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxymethyl]-benzofuran in 44% yield的产率得到3-methyl-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenoxymethyl]benzofuran
  参考文献：
  名称：

  Biaryl sulfonamides and methods for using same

  摘要：

  本发明涉及双芳基磺酰胺及其用途，例如，作为金属蛋白酶抑制剂。

  公开号：

  US07420001B2

文献信息

• Biaryl sulfonamides and methods for using same
  申请人：Xiang Shaoyun Jason

  公开号：US20050130973A1

  公开（公告）日：2005-06-16

  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 A. Elisabeth

  公开号：US20060004066A1

  公开（公告）日：2006-01-05

  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，特别是骨关节炎的方法，包括向患有该疾病的受试者施用能够调节ADMATS-5活性的药物。该药物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，骨关节炎程度降低。此外，与WT动物相比，ADAMTS-5转基因动物在关节组织中的聚集素酶活性降低。这些动物是ADAMTS-5相关疾病的良好模型，并可用于筛选用于治疗和/或预防这些疾病的药物。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，特别是能够抑制ADAMTS-5聚集素酶活性的药物，可以预防和/或治疗骨关节炎。
• 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.