N-(2-氯乙基)-10,11-二羟基去甲阿朴啡 | 75946-94-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 阿朴菲
• 中文名称: N-(2-氯乙基)-10,11-二羟基去甲阿朴啡
• 英文名称: (-)-N-(2-chloroethyl)norapomorphine
• 英文别名: N-Chloroethylnorapomorphine；[3H]-N-Chloroethylnorapomorphine；Chloroethylnorapomorphine；(6aR)-6-(2-chloroethyl)-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-10,11-diol
• CAS: 75946-94-0
• 化学式: C₁₈H₁₈ClNO₂
• 分子量: 315.799
• InChiKey: RMKWDBUEXHJPRZ-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  43.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(2-氯乙基)-10,11-二羟基去甲阿朴啡 在 acetate buffer 作用下， 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  Aporphines。50. N-（2-氯乙基）norapomorphine（一种不可逆的多巴胺受体拮抗剂）的溶剂分解动力学。

  摘要：

  （-）-N-（2-氯乙基）norapomorphine（NCA，1c）在水溶液中的溶剂分解速率和机理已通过反相液相色谱（HPLC）进行了追踪，以追踪起始原料和产物的水平。在pH值为7.0的25和37摄氏度下形成叠氮鎓离子的一级速率常数分别为0.024和0.096 min-1。确定NCA消失作为pH的函数的一级速率常数，可以计算出叔胺的pKa约为6.3，而反应条件（例如pH，缓冲盐和浓度，以及在产品分布上添加了亲核试剂）支持了这样的观点，即NCA溶剂分解是通过中间的叠氮鎓离子进行的。HPLC程序的应用使我们能够同时观察NCA的损失以及中间和多种产物的痕量水平。它还可以轻松分离并随后鉴定少量水解产物。在pH值为7时，仅在37°C下10分钟后和1 h后在25°C下达到最大叠氮鎓浓度。温度和pH值的升高促进了氮丙啶鎓离子以及非多巴胺拮抗剂溶剂分解产物的形成速率。讨论了这些发现的意义，包括缓冲离子添

  DOI：

  10.1021/jm00364a003
• 作为产物：
  描述：

  N-(2-hydroxyethyl)norapomorphine hydrochloride 在 palladium on activated charcoal 、 氯化亚砜 、 氢气 、 溴 、 三氟乙酸 作用下， 生成 N-(2-氯乙基)-10,11-二羟基去甲阿朴啡
  参考文献：
  名称：

  Aporphines. 58. N-(2-Chloroethyl)[8,9-2H]norapomorphine, an irreversible ligand for dopamine receptors: synthesis and application

  摘要：

  The synthesis of the title compounds (1c and its 2H isomer 1b) from N-(2-hydroxyethyl)norapomorphine was carried out by ring bromination, followed by chlorination to the 2-chloroethyl compound 6. Further reduction with 2H2 or 3H2 and Pd/C gave 1b or 1c. Radiochemically pure (97%) 1c was obtained with a specific activity of 16.3 Ci/mmol. The purity of 1c was determined by LC, HPLC, UV, and NMR. [3H]NCA was shown to label the D2 receptor; however, the D2 signal appears to be only a small portion of the total signal, which may include binding to other dopamine receptor subtypes (D1 and D3).

  DOI：

  10.1021/jm00372a019

文献信息

• Methods and compositions for treating cancer using P2RX2 inhibitors
  申请人：Flagship Pioneering Innovations V, Inc.

  公开号：US10457740B1

  公开（公告）日：2019-10-29

  The present invention provides methods for treating cancer using P2RX2 inhibitors, such as P2RX2 inhibitory antibodies, among others. The invention also features compositions containing P2RX2 inhibitors, methods of diagnosing patients with P2RX2-associated cancer, and methods of predicting the response of cancer in a subject to treatment with P2RX2 inhibitors.

  本发明提供了使用 P2RX2 抑制剂（如 P2RX2 抑制抗体等）治疗癌症的方法。本发明还包括含有 P2RX2 抑制剂的组合物、诊断 P2RX2 相关癌症患者的方法以及预测癌症对 P2RX2 抑制剂治疗的反应的方法。
• Methods for treating cancer using GRM8 inhibitors
  申请人：Flagship Pioneering Innovations V, Inc.

  公开号：US10683352B1

  公开（公告）日：2020-06-16

  The present invention provides methods for treating cancer using mGluR8 inhibitors, such as mGluR8 inhibitory antibodies and small molecules. The invention also features compositions containing mGluR8 inhibitors, methods of diagnosing patients with mGluR8-associated cancer, and methods of predicting the response of cancer in a subject to treatment with mGluR8 inhibitors.

  本发明提供了使用mGluR8抑制剂（如mGluR8抑制抗体和小分子）治疗癌症的方法。本发明还包括含有 mGluR8 抑制剂的组合物、诊断 mGluR8 相关癌症患者的方法以及预测癌症对 mGluR8 抑制剂治疗的反应的方法。
• Methods and compositions for treating cancer using SERCA pump inhibitors
  申请人：Flagship Pioneering Innovations V, Inc.

  公开号：US11013717B1

  公开（公告）日：2021-05-25

  The present invention provides methods for treating cancer using sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump inhibitors, such as SERCA pump inhibitory antibodies, among others. The invention also features compositions containing SERCA pump inhibitors, methods of diagnosing patients with SERCA pump-associated cancer, and methods of predicting the response of cancer in a subject to treatment with SERCA pump inhibitors.

  本发明提供了使用肌浆/内质网Ca2+-ATP酶（SERCA）泵抑制剂（如SERCA泵抑制抗体等）治疗癌症的方法。本发明还包括含有 SERCA 泵抑制剂的组合物、诊断 SERCA 泵相关癌症患者的方法以及预测癌症对 SERCA 泵抑制剂治疗的反应的方法。
• Methods and compositions for treating cancer using serotonin receptor inhibitors
  申请人：Flagship Pioneering Innovations V, Inc.

  公开号：US11034751B1

  公开（公告）日：2021-06-15

  The present invention provides methods for treating cancer using serotonin receptor inhibitors, such as serotonin receptor inhibitory antibodies, among others. The invention also features compositions containing serotonin receptor inhibitors, methods of diagnosing patients with serotonin receptor-associated cancer, and methods of predicting the response of cancer in a subject to treatment with serotonin receptor inhibitors.

  本发明提供了使用血清素受体抑制剂（如血清素受体抑制抗体等）治疗癌症的方法。本发明还包括含有血清素受体抑制剂的组合物、诊断血清素受体相关癌症患者的方法，以及预测癌症对血清素受体抑制剂治疗的反应的方法。
• Methods and compositions for treating inflammatory or autoimmune diseases or conditions using GRM8 activators
  申请人：Flagship Pioneering Innovations V, Inc.

  公开号：US11059886B1

  公开（公告）日：2021-07-13

  The present invention provides methods for treating inflammatory or autoimmune disease using mGluR8 activators, such as mGluR8 activating antibodies, among others. The invention also features compositions containing mGluR8 activators, methods of diagnosing patients with mGluR8-associated inflammatory or autoimmune disease, and methods of predicting the response of an inflammatory or autoimmune disease or condition in a subject to treatment with mGluR8 activators.

  本发明提供了使用mGluR8激活剂（如mGluR8激活抗体等）治疗炎症或自身免疫性疾病的方法。本发明还包括含有 mGluR8 激活剂的组合物、诊断 mGluR8 相关炎症或自身免疫性疾病患者的方法，以及预测受试者的炎症或自身免疫性疾病或病症对 mGluR8 激活剂治疗的反应的方法。