1-(6-ethoxynaphthalen-2-yl)-3-(piperidin-4-ylmethyl)imidazo[1,5-a]pyrazin-8-amine | 1574257-98-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(6-ethoxynaphthalen-2-yl)-3-(piperidin-4-ylmethyl)imidazo[1,5-a]pyrazin-8-amine
• 英文别名: US10307425, Example 114
• CAS: 1574257-98-9
• 化学式: C₂₄H₂₇N₅O
• 分子量: 401.511
• InChiKey: NJLWNYVATPDXHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  77.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  在 盐酸 作用下， 以 水 为溶剂， 反应 24.0h， 生成 1-(6-ethoxynaphthalen-2-yl)-3-(piperidin-4-ylmethyl)imidazo[1,5-a]pyrazin-8-amine
  参考文献：
  名称：

  Development of potent and selective Plasmodium falciparum calcium-dependent protein kinase 4 (PfCDPK4) inhibitors that block the transmission of malaria to mosquitoes

  摘要：

  Malaria remains a major health concern for a large percentage of the world's population. While great strides have been made in reducing mortality due to malaria, new strategies and therapies are still needed. Therapies that are capable of blocking the transmission of Plasmodium parasites are particularly attractive, but only primaquine accomplishes this, and toxicity issues hamper its widespread use. In this study, we describe a series of pyrazolopyrimidine- and imidazopyrazine-based compounds that are potent inhibitors of PfCDPK4, which is a calcium-activated Plasmodium protein lcinase that is essential for exflagellation of male gametocytes. Thus, PfCDPK4 is essential for the sexual development of Plasmodium parasites and their ability to infect mosquitoes. We demonstrate that two structural features in the ATPbinding site of PfCDPK4 can be exploited in order to obtain potent and selective inhibitors of this enzyme. Furthermore, we demonstrate that pyrazolopyrimidine-based inhibitors that are potent inhibitors of the in vitro activity of PfCDPK4 are also able to block Plasmodium falciparum exflagellation with no observable toxicity to human cells. This medicinal chemistry effort serves as a valuable starting point in the development of safe, transmission-blocking agents for the control of malaria. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.12.048

文献信息

• [EN] BUMPED KINASE INHIBITOR COMPOSITIONS AND METHODS FOR TREATING CANCER<br/>[FR] COMPOSITIONS D'INHIBITEUR DE KINASE À BOSSES ET MÉTHODES DE TRAITEMENT DU CANCER
  申请人：UNIV WASHINGTON

  公开号：WO2016123151A1

  公开（公告）日：2016-08-04

  The present disclosure is generally directed to bumped kinase inhibitor (BKI) compositions and methods for treating cancer.

  本公开涉及通常用于治疗癌症的凸起激酶抑制剂（BKI）组合物和方法。
• Bumped kinase inhibitor compositions and methods for treating cancer
  申请人：UNIVERSITY OF WASHINGTON

  公开号：US10350211B2

  公开（公告）日：2019-07-16

  The present disclosure is generally directed to bumped kinase inhibitor (BKI) compositions and methods for treating cancer.

  本公开总体上针对治疗癌症的撞击激酶抑制剂（BKI）组合物和方法。
• COMPOSITIONS AND METHODS FOR TREATING TOXOPLASMOSIS, CRYPTOSPORIDIOSIS AND OTHER APICOMPLEXAN PROTOZOAN RELATED DISEASES
  申请人：University of Washington

  公开号：EP3250290A1

  公开（公告）日：2017-12-06
• BUMPED KINASE INHIBITOR COMPOSITIONS AND METHODS FOR TREATING CANCER
  申请人：UNIVERSITY OF WASHINGTON

  公开号：US20180271871A1

  公开（公告）日：2018-09-27

  The present disclosure is generally directed to bumped kinase inhibitor (BKI) compositions and methods for treating cancer.
• [EN] COMPOSITIONS AND METHODS FOR TREATING TOXOPLASMOSIS, CRYPTOSPORIDIOSIS AND OTHER APICOMPLEXAN PROTOZOAN RELATED DISEASES<br/>[FR] COMPOSITIONS ET MÉTHODES DE TRAITEMENT DE LA TOXOPLASMOSE, DE LA CRYPTOSPORIDIOSE ET D'AUTRES MALADIES ASSOCIÉES À UN PROTOZOAIRE APICOMPLEXE
  申请人：UNIV WASHINGTON

  公开号：WO2016123152A1

  公开（公告）日：2016-08-04

  The present disclosure is directed to compositions and methods for inhibiting either Toxoplasma gondii (T. gondii) calcium dependent protein kinases (TgCDPKs) or Cryptosporidium parvum (C. parvum) and Cryptosporidium hominus (C. hominus) calcium dependent protein kinases (CpCDPKs) using pyrazolopyrimidine and/or imidazo[1,5-α]pyrazine inhibitors, of the Formula (I), wherein the variables X, Y, Z, R1, and R3 are defined herein.