(R)-5-chloro-1-(1-cyclopropyl-2-methoxyethyl)-3-(4-hydroxy-2,5-dimethylphenylamino)pyrazin-2(1H)-one | 1173523-81-3

• 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: (R)-5-chloro-1-(1-cyclopropyl-2-methoxyethyl)-3-(4-hydroxy-2,5-dimethylphenylamino)pyrazin-2(1H)-one
• 英文别名: 5-chloro-1-[(1R)-1-cyclopropyl-2-methoxyethyl]-3-(4-hydroxy-2,5-dimethylanilino)pyrazin-2-one
• CAS: 1173523-81-3
• 化学式: C₁₈H₂₂ClN₃O₃
• 分子量: 363.844
• InChiKey: YUBKTSIORXXQNZ-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  74.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  溴氟甲烷 、 (R)-5-chloro-1-(1-cyclopropyl-2-methoxyethyl)-3-(4-hydroxy-2,5-dimethylphenylamino)pyrazin-2(1H)-one 在 potassium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 生成 5-chloro-1-[(1R)-1-cyclopropyl-2-methoxyethyl]-3-[4-(fluoromethoxy)-2,5-dimethylanilino]pyrazin-2-one
  参考文献：
  名称：

  [18F](R)-5-chloro-1-(1-cyclopropyl-2-methoxyethyl)-3-(4-(2-fluoroethoxy)-2,5-dimethyl phenylamino)pyrazin-2(1H)-one: Introduction of N3-phenylpyrazinones as potential CRF-R1 PET imaging agents

  摘要：

  Based on a favorable balance between CRF-R1 affinity, lipophilicity and metabolic stability, compound 10 was evaluated for potential development as PET radioligand. Compound [F-18]10 was prepared with high radiochemical purity and showed promising binding properties in rat brain imaging experiments. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.112
• 作为产物：
  描述：

  4-甲氧基-2,5-二甲基苯胺 在 sodium hexamethyldisilazane 、 三溴化硼 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (R)-5-chloro-1-(1-cyclopropyl-2-methoxyethyl)-3-(4-hydroxy-2,5-dimethylphenylamino)pyrazin-2(1H)-one
  参考文献：
  名称：

  [18F](R)-5-chloro-1-(1-cyclopropyl-2-methoxyethyl)-3-(4-(2-fluoroethoxy)-2,5-dimethyl phenylamino)pyrazin-2(1H)-one: Introduction of N3-phenylpyrazinones as potential CRF-R1 PET imaging agents

  摘要：

  Based on a favorable balance between CRF-R1 affinity, lipophilicity and metabolic stability, compound 10 was evaluated for potential development as PET radioligand. Compound [F-18]10 was prepared with high radiochemical purity and showed promising binding properties in rat brain imaging experiments. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.112

文献信息

• Synthesis, Structure−Activity Relationships, and In Vivo Evaluation of <i>N</i>³-Phenylpyrazinones as Novel Corticotropin-Releasing Factor-1 (CRF₁) Receptor Antagonists
  作者：Richard A. Hartz、Vijay T. Ahuja、Argyrios G. Arvanitis、Maria Rafalski、Eddy W. Yue、Derek J. Denhart、William D. Schmitz、Jonathan L. Ditta、Jeffrey A. Deskus、Allison B. Brenner、Frank W. Hobbs、Joseph Payne、Snjezana Lelas、Yu-Wen Li、Thaddeus F. Molski、Gail K. Mattson、Yong Peng、Harvey Wong、James E. Grace、Kimberley A. Lentz、Jingfang Qian-Cutrone、Xiaoliang Zhuo、Yue-Zhong Shu、Nicholas J. Lodge、Robert Zaczek、Andrew P. Combs、Richard E. Olson、Joanne J. Bronson、Ronald J. Mattson、John E. Macor

  DOI：10.1021/jm900301y

  日期：2009.7.23

  Evidence suggests that corticotropin-releasing factor-1 (CRF1) receptor antagonists may offer therapeutic potential for the treatment of diseases associated with elevated levels of CRF such as anxiety and depression. A pyrazinone-based chemotype of CRF1 receptor antagonists was discovered. Structure−activity relationship studies led to the identification of numerous potent analogues including 12p,

  有证据表明，促肾上腺皮质激素释放因子1（CRF 1）受体拮抗剂可能为治疗与CRF水平升高有关的疾病（如焦虑症和抑郁症）提供治疗潜力。发现了基于吡嗪酮的CRF 1受体拮抗剂的化学型。结构-活性关系研究导致鉴定出许多有效的类似物，包括12p，这是一种高效和选择性的CRF 1受体拮抗剂，IC 50值为0.26 nM。在大鼠和食蟹猴中评估了12p的药代动力学特性。复合12p对大鼠的防御性戒断试验（焦虑症动物模型）有效。描述了吡嗪酮化学型内化合物的合成，构效关系和体内性质。