N-(8-hydroxyquinolin-5-yl)-[1,1'-biphenyl]-4-sulfonamide | 1262633-07-7

• 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: N-(8-hydroxyquinolin-5-yl)-[1,1'-biphenyl]-4-sulfonamide
• 英文别名: biphenyl-4-sulfonic acid (8-hydroxyquinolin-5-yl)amide；N-(8-hydroxyquinolin-5-yl)biphenyl-4-sulfonamide；N-(8-Hydroxyquinolin-5-yl)-[1,1''-biphenyl]-4-sulfonamide；N-(8-hydroxyquinolin-5-yl)-4-phenylbenzenesulfonamide
• CAS: 1262633-07-7
• 化学式: C₂₁H₁₆N₂O₃S
• 分子量: 376.436
• InChiKey: OQFSPTGJLFPDPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  87.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  对联苯磺酰氯 、 5-amino-8-hydroxyquinoline dihydrochloride 在 吡啶 作用下， 反应 16.0h， 以37%的产率得到N-(8-hydroxyquinolin-5-yl)-[1,1'-biphenyl]-4-sulfonamide
  参考文献：
  名称：

  Identifying Chelators for Metalloprotein Inhibitors Using a Fragment-Based Approach

  摘要：

  Fragment-based lead design (FBLD) has been used to identify new metal-binding groups for metalloenzyme inhibitors. When screened at 1 mM, a chelator fragment library (CFL-1.1) of 96 compounds produced hit rates ranging from 29% to 43% for five matrix metalloproteases (MMPs), 24% for anthrax lethal factor (LF), 49% for 5-lipoxygenase (5-LO), and 60% for tyrosinase (TY). The ligand efficiencies (LE) of the fragment hits are excellent, in the range of 0.4-0.8 kcal/mol. The MMP enzymes all generally elicit the same chelators as hits from CFL-1.1; however, the chelator fragments that inhibit structurally unrelated metalloenzymes (LF, 5-LO, TY) vary considerably. To develop more advanced hits, one hit from CFL-1.1, 8-hydroxyquinoline, was elaborated at four different positions around the ring system to generate new fragments. 8-Hydroxyquinoline fragments substituted at either the 5- or 7-positions gave potent hits against MMP-2, with IC50 values in the low micromolar range. The 8-hydroxyquinoline represents a promising new chelator scaffold for the development of MMP inhibitors that was discovered by use of a metalloprotein-focused chelator fragment library.

  DOI：

  10.1021/jm101266s

文献信息

• PHARMACEUTICAL COMPOSITION WITH ENHANCED EFFICACY FOR INHIBITING ANGIOGENESIS
  申请人：Kwon Ho Jeong

  公开号：US20140315947A1

  公开（公告）日：2014-10-23

  The present invention relates to a pharmaceutical composition for inhibiting angiogenesis and a novel sulfonyl amide derivative compound which can be useful for the prevention or treatment of angiogenesis-related diseases or disorders. Since the compound used as an active ingredient in the pharmaceutical composition of the invention is specifically bound to UQCRB and inhibits biological functions thereof, apoptosis is not induced and angiogenic responses are inhibited. Therefore, the compound used as an active ingredient in the pharmaceutical composition of the invention can be useful as an effective and safe angiogenesis inhibitory agent.

  本发明涉及一种用于抑制血管生成的药物组合物以及一种新型磺酰胺衍生物化合物，该化合物可用于预防或治疗与血管生成相关的疾病或疾病。由于本发明药物组合物中所使用的活性成分化合物特异地结合到UQCRB并抑制其生物功能，不会诱导凋亡并抑制血管生成反应。因此，本发明药物组合物中所使用的活性成分化合物可以作为一种有效且安全的抑制血管生成的药剂。
• Development of a Novel Class of Mitochondrial Ubiquinol–Cytochrome <i>c</i> Reductase Binding Protein (UQCRB) Modulators as Promising Antiangiogenic Leads
  作者：Hye Jin Jung、Misun Cho、Yonghyo Kim、Gyoonhee Han、Ho Jeong Kwon

  DOI：10.1021/jm500863j

  日期：2014.10.9

  Recently we identified a novel therapeutic target and small molecule for regulating angiogenesis. Our study showed that ubiquinol-cytochrome c-reductase binding protein (UQCRB) of the mitochondrial complex III plays a crucial role in hypoxia-induced angiogenesis via mitochondrial reactive oxygen species (ROS) mediated signaling. Herein, we developed new synthetic small molecules that specifically bind to UQCRB and regulate its function. To improve the pharmacological properties of 6-((1-hydroxynaphthalen 4-ylamino)dioxysulfone) 2H naphtho[1,8-bc]thiophen-2-one (HDNT), a small molecule that targets UQCRB, a series of HDNT derivatives were designed and synthesied. Several derivatives showed a significant increase in hypoxia inducible factor 1 alpha (HIF-1 alpha) inhibitory potency. compared to HDNT. The compounds bound to UQCRB and suppressed mitochondrial ROS-mediated hypoxic signaling, resulting in potent inhibitor of angiogenesis without inducing cytotoxicity. Notably, one of these new derivatives significantly suppressed tumor growth in a mouse xenograft model. Therefore, these mitochondrial UQCRB modulators could be potential leads for the development of novel antiangiogen agents.
• US9371286B2
  申请人：——

  公开号：US9371286B2

  公开（公告）日：2016-06-21
• Identifying Chelators for Metalloprotein Inhibitors Using a Fragment-Based Approach
  作者：Jennifer A. Jacobsen、Jessica L. Fullagar、Melissa T. Miller、Seth M. Cohen

  DOI：10.1021/jm101266s

  日期：2011.1.27

  Fragment-based lead design (FBLD) has been used to identify new metal-binding groups for metalloenzyme inhibitors. When screened at 1 mM, a chelator fragment library (CFL-1.1) of 96 compounds produced hit rates ranging from 29% to 43% for five matrix metalloproteases (MMPs), 24% for anthrax lethal factor (LF), 49% for 5-lipoxygenase (5-LO), and 60% for tyrosinase (TY). The ligand efficiencies (LE) of the fragment hits are excellent, in the range of 0.4-0.8 kcal/mol. The MMP enzymes all generally elicit the same chelators as hits from CFL-1.1; however, the chelator fragments that inhibit structurally unrelated metalloenzymes (LF, 5-LO, TY) vary considerably. To develop more advanced hits, one hit from CFL-1.1, 8-hydroxyquinoline, was elaborated at four different positions around the ring system to generate new fragments. 8-Hydroxyquinoline fragments substituted at either the 5- or 7-positions gave potent hits against MMP-2, with IC50 values in the low micromolar range. The 8-hydroxyquinoline represents a promising new chelator scaffold for the development of MMP inhibitors that was discovered by use of a metalloprotein-focused chelator fragment library.