3-iodo-4-oxo-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrazine-2-carboxylic acid ethyl ester | 1382786-17-5

• 分子结构分类: 有机化合物
• 英文名称: 3-iodo-4-oxo-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrazine-2-carboxylic acid ethyl ester
• 英文别名: ethyl 3-iodo-4-oxo-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazine-2-carboxylate
• CAS: 1382786-17-5
• 化学式: C₉H₁₀IN₃O₃
• 分子量: 335.101
• InChiKey: JJCOWPIIQQEFQK-UHFFFAOYSA-N

物化性质

• 沸点：
  553.5±50.0 °C(Predicted)
• 密度：
  2.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  73.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-iodo-4-oxo-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrazine-2-carboxylic acid ethyl ester 在 lithium aluminium tetrahydride 、 偶氮二甲酸二叔丁酯 、 palladium diacetate 、 potassium carbonate 、 三苯基膦 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 20.5h， 生成 3-methyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one
  参考文献：
  名称：

  Preliminary investigation of 6,7-dihydropyrazolo[1,5- a ]pyrazin-4-one derivatives as a novel series of mGlu 5 receptor positive allosteric modulators with efficacy in preclinical models of schizophrenia

  摘要：

  As part of our efforts to identify a suitable back-up compound to our recently disclosed mGlu(5) positive allosteric modulator (PAM) clinical candidate VU0490551/JNJ-46778212, this letter details the investigation and challenges of a novel series of 6,7-dihydropyrazolo[1,5-a]pyrazin-4-one derivatives. From these efforts, compound 4k emerged as a potent and selective mGlu(5) PAM displaying overall attractive in vitro (pharmacological and ADMET) and PK profiles combined with in vivo efficacy in preclinical models of schizophrenia. However, further advancement of the compound was precluded due to severely limiting CNS-related side-effects confirming the previously reported association between excessive mGlu(5) activation and target-related toxicities. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.11.098
• 作为产物：
  描述：

  3,5-吡唑羧酸二乙酯 在 盐酸 、 ammonium cerium (IV) nitrate 、 碘 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 3-iodo-4-oxo-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrazine-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  新規ヘテロ芳香族アミド誘導体又はその塩からなる医薬

  摘要：

  本文提供了一种用于治疗或预防与疼痛相关疾病、瘙痒相关疾病、自主神经相关疾病等的与电位依赖性钠通道（Nav1.7）有关的化合物或其药物组合物。具体化合物及其包含的药物组合物如下所示。【选择图】无

  公开号：

  JP2021138690A

文献信息

• [EN] BICYCLIC TRIAZOLE AND PYRAZOLE LACTAMS AS ALLOSTERIC MODULATORS OF MGLUR5 RECEPTORS<br/>[FR] UTILISATION DE LACTAMES DE TRIAZOLE ET DE PYRAZOLE BICYCLIQUES COMME MODULATEURS ALLOSTÉRIQUES DES RÉCEPTEURS MGLUR5
  申请人：UNIV VANDERBILT

  公开号：WO2012083224A1

  公开（公告）日：2012-06-21

  In one aspect, the invention relates to bicyclic triazole and pyrazole lactams, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在一个方面，该发明涉及到双环三唑和吡唑内酰胺，它们的衍生物以及相关化合物，这些化合物可用作代谢型谷氨酸受体亚型5（mGluR5）的正向变构调节剂；制备这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗与谷氨酸功能障碍相关的神经和精神疾病的方法。本摘要旨在作为在特定领域进行搜索的扫描工具，并不意味着对本发明的限制。
• BICYCLIC TRIAZOLE AND PYRAZOLE LACTAMS AS ALLOSTERIC MODULATORS OF MGLUR5 RECEPTORS
  申请人：Conn P. Jeffrey

  公开号：US20120225844A1

  公开（公告）日：2012-09-06

  In one aspect, the invention relates to bicyclic triazole and pyrazole lactams, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  本发明涉及双环三唑和吡唑内酰胺、其衍生物和相关化合物，可作为代谢型谷氨酸受体亚型5（mGluR5）的正向变构调节剂；制备这些化合物的合成方法；包含这些化合物的制药组合物；以及使用这些化合物和组合物治疗与谷氨酸功能障碍相关的神经和精神障碍的方法。本摘要旨在作为特定领域搜索的扫描工具，不限制本发明。
• Bicyclic triazole and pyrazole lactams as allosteric modulators of mGluR5 receptors
  申请人：Conn P. Jeffrey

  公开号：US08592422B2

  公开（公告）日：2013-11-26

  In one aspect, the invention relates to bicyclic triazole and pyrazole lactams, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在某个方面，本发明涉及用作代谢型谷氨酸受体亚型5（mGluR5）正向变构调节剂的双环三唑和吡唑烯酮及其衍生物和相关化合物；制备该化合物的合成方法；包含该化合物的制药组合物；以及使用该化合物和组合物治疗与谷氨酸功能障碍相关的神经和精神障碍的方法。本摘要旨在作为特定领域搜索的扫描工具，不限制本发明。
• EP3851436
  申请人：——

  公开号：——

  公开（公告）日：——
• US8592422B2
  申请人：——

  公开号：US8592422B2

  公开（公告）日：2013-11-26