(7-bromo-1-oxo-1H-isoquinolin-2-yl)acetic acid | 1397196-09-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: (7-bromo-1-oxo-1H-isoquinolin-2-yl)acetic acid
• 英文别名: 2-(7-Bromo-1-oxoisoquinolin-2-yl)acetic acid；2-(7-bromo-1-oxoisoquinolin-2-yl)acetic acid
• CAS: 1397196-09-6
• 化学式: C₁₁H₈BrNO₃
• 分子量: 282.093
• InChiKey: GTLSYSAXYWLJSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (7-bromo-1-oxo-1H-isoquinolin-2-yl)acetic acid 在 盐酸 、 1-羟基苯并三唑 作用下， 以 甲醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 21.33h， 生成 R-1-[(7-bromo-1-oxo-1H-isoquinolin-2-yl)acetamido]-3-methylbutylboronic acid
  参考文献：
  名称：

  Optimization of peptidomimetic boronates bearing a P3 bicyclic scaffold as proteasome inhibitors

  摘要：

  A new series of pseudopeptide boronate proteasome inhibitors (2-3) was developed, through optimization of our previously described analogs of bortezomib, bearing a bicyclic 1,6-naphthyridin-5(6H)-one scaffold as P3 fragment (1). The biological evaluation on human 20S proteasome displayed a promising inhibition profile, especially for compounds bearing a P2 ethylene fragment, which exhibited Ki values in the nanomolar range for the ChT-L activity (e.g. 2a, Ki = 0.057 μM) and considerable selectivity for proteasome over bovine pancreatic α-chymotrypsin. Docking experiments into the yeast 20S proteasome revealed that the ligands are accommodated predominantly into the ChT-L site and that they covalently bind to the active site threonine residue via boron atom. Within the cellular assays performed against a 60 cancer cell line panel, compounds 3e and 3f demonstrated also good antiproliferative activity and compound 3f emerged as promising lead compound for the development of anticancer agents targeting melanoma and non-small cell lung cancer.

  DOI：

  10.1016/j.ejmech.2014.06.017
• 作为产物：
  描述：

  (7-bromo-1-oxo-1H-isoquinolin-2-yl)acetic acid ethyl ester 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以97%的产率得到(7-bromo-1-oxo-1H-isoquinolin-2-yl)acetic acid
  参考文献：
  名称：

  Optimization of peptidomimetic boronates bearing a P3 bicyclic scaffold as proteasome inhibitors

  摘要：

  A new series of pseudopeptide boronate proteasome inhibitors (2-3) was developed, through optimization of our previously described analogs of bortezomib, bearing a bicyclic 1,6-naphthyridin-5(6H)-one scaffold as P3 fragment (1). The biological evaluation on human 20S proteasome displayed a promising inhibition profile, especially for compounds bearing a P2 ethylene fragment, which exhibited Ki values in the nanomolar range for the ChT-L activity (e.g. 2a, Ki = 0.057 μM) and considerable selectivity for proteasome over bovine pancreatic α-chymotrypsin. Docking experiments into the yeast 20S proteasome revealed that the ligands are accommodated predominantly into the ChT-L site and that they covalently bind to the active site threonine residue via boron atom. Within the cellular assays performed against a 60 cancer cell line panel, compounds 3e and 3f demonstrated also good antiproliferative activity and compound 3f emerged as promising lead compound for the development of anticancer agents targeting melanoma and non-small cell lung cancer.

  DOI：

  10.1016/j.ejmech.2014.06.017

文献信息

• [EN] HETEROAROMATIC NMDA RECEPTOR MODULATORS AND USES THEREOF<br/>[FR] MODULATEURS DES RÉCEPTEURS NMDA HÉTÉROAROMATIQUES ET UTILISATIONS DE CEUX-CI
  申请人：LUC THERAPEUTICS

  公开号：WO2017100591A1

  公开（公告）日：2017-06-15

  Disclosed herein, in part, are heteroaromatic compounds and methods of use in treating neuropsychiatric disorders, e.g., schizophrenia and major depressive disorder. Pharmaceutical compositions and methods of making heteroaromatic compounds are provided. The compounds are contemplated modulate the NMDA receptor.

  本文披露了杂环芳烃化合物及其在治疗神经精神障碍，例如精神分裂症和重度抑郁症中的用途方法。提供了药物组合物和制备杂环芳烃化合物的方法。这些化合物被认为可以调节NMDA受体。
• Heteroaromatic NMDA receptor modulators and uses thereof
  申请人：Cadent Therapeutics, Inc.

  公开号：US10626122B2

  公开（公告）日：2020-04-21

  Disclosed herein, in part, are heteroaromatic compounds and methods of use in treating neuropsychiatric disorders, e.g., schizophrenia and major depressive disorder. Pharmaceutical compositions and methods of making heteroaromatic compounds are provided. The compounds are contemplated modulate the NMDA receptor.

  本文部分公开了杂芳香族化合物和用于治疗神经精神疾病（如精神分裂症和重度抑郁症）的方法。提供了药物组合物和制造杂芳香族化合物的方法。这些化合物可以调节 NMDA 受体。
• HETEROAROMATIC NMDA RECEPTOR MODULATORS AND USES THEREOF
  申请人：Cadent Therapeutics, Inc.

  公开号：EP3386591B1

  公开（公告）日：2020-06-24
• Optimization of peptidomimetic boronates bearing a P3 bicyclic scaffold as proteasome inhibitors
  作者：Valeria Troiano、Kety Scarbaci、Roberta Ettari、Nicola Micale、Carmen Cerchia、Andrea Pinto、Tanja Schirmeister、Ettore Novellino、Silvana Grasso、Antonio Lavecchia、Maria Zappalà

  DOI：10.1016/j.ejmech.2014.06.017

  日期：2014.8

  A new series of pseudopeptide boronate proteasome inhibitors (2-3) was developed, through optimization of our previously described analogs of bortezomib, bearing a bicyclic 1,6-naphthyridin-5(6H)-one scaffold as P3 fragment (1). The biological evaluation on human 20S proteasome displayed a promising inhibition profile, especially for compounds bearing a P2 ethylene fragment, which exhibited Ki values in the nanomolar range for the ChT-L activity (e.g. 2a, Ki = 0.057 μM) and considerable selectivity for proteasome over bovine pancreatic α-chymotrypsin. Docking experiments into the yeast 20S proteasome revealed that the ligands are accommodated predominantly into the ChT-L site and that they covalently bind to the active site threonine residue via boron atom. Within the cellular assays performed against a 60 cancer cell line panel, compounds 3e and 3f demonstrated also good antiproliferative activity and compound 3f emerged as promising lead compound for the development of anticancer agents targeting melanoma and non-small cell lung cancer.