3′-chloro-6-methoxy-[1,1′-biphenyl]-3-carboxylicacid | 1181359-77-2

• 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: 3′-chloro-6-methoxy-[1,1′-biphenyl]-3-carboxylicacid
• 英文别名: 3-(3-Chlorophenyl)-4-methoxybenzoic acid
• CAS: 1181359-77-2
• 化学式: C₁₄H₁₁ClO₃
• mdl: MFCD11895454
• 分子量: 262.693
• InChiKey: HMZUJVIKLNYFPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3′-chloro-6-methoxy-[1,1′-biphenyl]-3-carboxylicacid 在 叠氮磷酸二苯酯 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 1.0h， 生成 3-(3-chlorophenyl)-4-methoxybenzoyl azide
  参考文献：
  名称：

  Exploiting Conformational Dynamics in Drug Discovery: Design of C-Terminal Inhibitors of Hsp90 with Improved Activities

  摘要：

  The interaction that occurs between molecules is a dynamic process that impacts both structural and conformational properties of the ligand and the ligand binding site. Herein, we investigate the dynamic cross-talk between a protein and the ligand as a source for new opportunities in ligand design. Analysis of the formation/disappearance of protein pockets produced in response to a first-generation inhibitor assisted in the identification of functional groups that could be introduced onto scaffolds to facilitate optimal binding, which allowed for increased binding with previously uncharacterized regions. MD simulations were used to elucidate primary changes that occur in the Hsp90 C-terminal binding pocket in the presence of first-generation ligands. This data was then used to design ligands that adapt to these receptor conformations, which provides access to an energy landscape that is not visible in a static model. The newly synthesized compounds demonstrated antiproliferative activity at similar to 150 nM concentration. The method identified herein may be used to design chemical probes that provide additional information on structural variations of Hsp90 C-terminal binding site.

  DOI：

  10.1021/ci4005767
• 作为产物：
  描述：

  在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 以451 mg的产率得到3′-chloro-6-methoxy-[1,1′-biphenyl]-3-carboxylicacid
  参考文献：
  名称：

  Exploiting Conformational Dynamics in Drug Discovery: Design of C-Terminal Inhibitors of Hsp90 with Improved Activities

  摘要：

  The interaction that occurs between molecules is a dynamic process that impacts both structural and conformational properties of the ligand and the ligand binding site. Herein, we investigate the dynamic cross-talk between a protein and the ligand as a source for new opportunities in ligand design. Analysis of the formation/disappearance of protein pockets produced in response to a first-generation inhibitor assisted in the identification of functional groups that could be introduced onto scaffolds to facilitate optimal binding, which allowed for increased binding with previously uncharacterized regions. MD simulations were used to elucidate primary changes that occur in the Hsp90 C-terminal binding pocket in the presence of first-generation ligands. This data was then used to design ligands that adapt to these receptor conformations, which provides access to an energy landscape that is not visible in a static model. The newly synthesized compounds demonstrated antiproliferative activity at similar to 150 nM concentration. The method identified herein may be used to design chemical probes that provide additional information on structural variations of Hsp90 C-terminal binding site.

  DOI：

  10.1021/ci4005767

文献信息

• [EN] ARYL-1,3-AZOLE DERIVATIVES AND METHODS FOR INHIBITING HEPARNASE ACTIVITY<br/>[FR] DERIVES D'ARYL-1,3-AZOLE ET PROCEDES PERMETTANT D'INHIBER L'ACTIVITE DE L'HEPARANASE
  申请人：IMCLONE SYSTEMS INC

  公开号：WO2005030206A1

  公开（公告）日：2005-04-07

  The present invention encompasses heparanase inhibitors, particularly to certain 2-substituted heteroaryl-fused and aryl-fused carbazole derivatives that inhibit heparanase, pharmaceutical compositions that contain the compounds, methods for making the compounds, and methods of treating heparanase-dependent diseases and conditions in mammals by administering a therapeutically effective amount of the compounds to the mammals.

  本发明涵盖了抑制肝素酶的抑制剂，特别是特定的2-取代杂芳基融合和芳基融合的咔唑衍生物，这些衍生物抑制肝素酶，包含这些化合物的药物组合物，制备这些化合物的方法，以及通过向哺乳动物施用这些化合物的治疗有效量来治疗依赖肝素酶的疾病和病况的方法。