4-(5-chloro-2-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidin-7-yl)morpholine | 1232224-69-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 4-(5-chloro-2-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidin-7-yl)morpholine
• 英文别名: 4-(5-Chloro-2-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidin-7-yl)morpholine；4-(5-chloro-2-pyridin-4-ylpyrazolo[1,5-a]pyrimidin-7-yl)morpholine
• CAS: 1232224-69-9
• 化学式: C₁₅H₁₄ClN₅O
• 分子量: 315.762
• InChiKey: BTWMFATXLNSDKY-UHFFFAOYSA-N

物化性质

• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  55.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(5-chloro-2-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidin-7-yl)morpholine 在 一水合肼 作用下， 以 1,4-二氧六环 为溶剂， 反应 10.0h， 生成 4-(5-hydrazinyl-2-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidin-7-yl)morpholine
  参考文献：
  名称：

  PYRAZOLO-PYRIMIDINE COMPOUNDS

  摘要：

  本发明已经寻找到多种显示IL-12/IL-23产生抑制活性的化合物，并在此提供了包括该化合物的用于预防或治疗IL-12/IL-23过度产生相关疾病的药物组合物和药剂。

  公开号：

  US20110294781A1
• 作为产物：
  描述：

  异烟酸乙酯 在 18-冠醚-6 potassium tert-butylate 、 sodium ethanolate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， 反应 34.58h， 生成 4-(5-chloro-2-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidin-7-yl)morpholine
  参考文献：
  名称：

  PYRAZOLO-PYRIMIDINE COMPOUNDS

  摘要：

  本发明已经寻找到多种显示IL-12/IL-23产生抑制活性的化合物，并在此提供了包括该化合物的用于预防或治疗IL-12/IL-23过度产生相关疾病的药物组合物和药剂。

  公开号：

  US20110294781A1

文献信息

• [EN] SUBSTITUTED PYRAZOLO-PYRIMIDINES AND USES THEREOF<br/>[FR] PYRAZOLO-PYRIMIDINES SUBSTITUÉES ET LEURS UTILISATIONS
  申请人：VERGE ANALYTICS INC

  公开号：WO2021146192A1

  公开（公告）日：2021-07-22

  The present disclosure provides compounds that are inhibitors of PIKfyve kinases useful for the treatment of neurological diseases treatable by inhibition of PIKfyve. Also provided are pharmaceutical compositions containing such compounds, and methods of treatment using such compounds.

  本公开提供了一些抑制PIKfyve激酶的化合物，可用于治疗通过抑制PIKfyve来治疗的神经系统疾病。还提供了含有这些化合物的药物组合物，以及使用这些化合物进行治疗的方法。
• [EN] NOVEL INHIBITORS OF PIKFYVE AND METHODS USING SAME<br/>[FR] NOUVEAUX INHIBITEURS DE LA PIKFYVE ET LEURS MÉTHODES D'UTILISATION
  申请人：TME THERAPEUTICS LLC

  公开号：WO2022086993A1

  公开（公告）日：2022-04-28

  The invention relates to novel inhibitors of the PIKFYVE, a phosphoinositide kinase, useful for the treatment of diseases or disorders characterized by dysregulation of phosphoinositide mediated signal transduction pathways, including hyperproliferative diseases, autoimmune diseases, Crohn's disease, psoriasis, neurological diseases, diabetes, corneal fleck dystrophy, and viral infection (including HIV, Ebola, and coronavirus infections). The invention further relates to pharmaceutical compositions comprising PIKFYVE inhibitors and methods of treatment of such diseases and disorders.

  该发明涉及一种新型PIKFYVE抑制剂，它是一种磷脂酰肌醇激酶，可用于治疗由于磷脂酰肌醇介导的信号转导通路失调所导致的疾病或障碍，包括增殖过度性疾病、自身免疫性疾病、克罗恩病、银屑病、神经系统疾病、糖尿病、角膜斑点萎缩症和病毒感染（包括HIV、埃博拉和冠状病毒感染）。该发明还涉及包含PIKFYVE抑制剂的制药组合物和治疗上述疾病和障碍的方法。
• SCREENING METHOD
  申请人：Takeshita Sen

  公开号：US20130017548A1

  公开（公告）日：2013-01-17

  The present invention relates to a novel method for screening for a therapeutic or prophylactic agent for an inflammatory disease. More particularly, the present invention relates to a method for screening for a therapeutic or prophylactic agent for an inflammatory disease by selecting a substance having an inhibitory activity specific to PIKfyve by using the presence or absence of the inhibitory activity as an indicator.

  本发明涉及一种新的筛选治疗或预防炎症性疾病的药物的方法。更具体地说，本发明涉及一种通过选择具有特异性抑制PIKfyve的物质并使用抑制活性的存在或缺失作为指标来筛选治疗或预防炎症性疾病的药物的方法。
• [EN] METHODS AND TREATMENT OF VIRAL INFECTION WITH SUBSTITUTED PYRAZOLO-PYRIMIDINES<br/>[FR] PROCÉDÉS ET TRAITEMENT D'INFECTION VIRALE AVEC DES PYRAZOLO-PYRIMIDINES SUBSTITUÉES
  申请人：VERGE ANALYTICS INC

  公开号：WO2022261069A1

  公开（公告）日：2022-12-15

  The present disclosure provides compounds that are useful for the treatment of certain coronavirus infections.

  本公开提供了一些化合物，可用于治疗某些冠状病毒感染。
• Structure–activity relationship study, target identification, and pharmacological characterization of a small molecular IL-12/23 inhibitor, APY0201
  作者：Nobuhiko Hayakawa、Masatsugu Noguchi、Sen Takeshita、Agung Eviryanti、Yukie Seki、Hikaru Nishio、Ryohei Yokoyama、Misato Noguchi、Manami Shuto、Yoichiro Shima、Kanna Kuribayashi、Shunsuke Kageyama、Hiroyuki Eda、Manabu Suzuki、Tomohisa Hatta、Shun-ichiro Iemura、Tohru Natsume、Itsuya Tanabe、Ryusuke Nakagawa、Makoto Shiozaki、Kuniya Sakurai、Masataka Shoji、Ayatoshi Andou、Takashi Yamamoto

  DOI：10.1016/j.bmc.2014.03.036

  日期：2014.6

  Interleukin-12 (IL-12) and IL-23 are proinflammatory cytokines and therapeutic targets for inflammatory and autoimmune diseases, including inflammatory bowel diseases, psoriasis, rheumatoid arthritis, and multiple sclerosis. We describe the discovery of APY0201, a unique small molecular IL-12/23 production inhibitor, from activated macrophages and monocytes, and demonstrate ameliorated inflammation in an experimental model of colitis. Through a chemical proteomics approach using a highly sensitive direct nanoflow LC-MS/MS system and bait compounds equipped with the FLAG epitope associated regulator of PIKfyve (ArPIKfyve) was detected. Further study identified its associated protein phosphoinositide kinase, FYVE finger-containing (PIKfyve), as the target protein of APY0201, which was characterized as a potent, highly selective, ATP-competitive PIKfyve inhibitor that interrupts the conversion of phosphatidylinositol 3-phosphate (PtdIns3P) to PtdIns(3,5)P-2. These results elucidate the function of PIKfyve kinase in the IL-12/23 production pathway and in IL-12/23-driven inflammatory disease pathologies to provide a compelling rationale for targeting PIKfyve kinase in inflammatory and autoimmune diseases. (C) 2014 Elsevier Ltd. All rights reserved.