EC3016 | 1119222-18-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: EC3016
• 英文别名: EC017；N(4-(4-amino-1-tert-butyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenyl)cyclopentanecarboxamide；N-(4-(4-amino-1-tert-butyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenyl)cyclopentanecarboxamide；N-[4-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)phenyl]cyclopentanecarboxamide
• CAS: 1119222-18-2
• 化学式: C₂₁H₂₆N₆O
• 分子量: 378.477
• InChiKey: JHFJTTIYEGPPOW-UHFFFAOYSA-N

物化性质

• 沸点：
  645.9±55.0 °C(predicted)
• 密度：
  1.33±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  98.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  环戊基甲酰氯 、 EC3016 在 吡啶 作用下， 生成 EC049
  参考文献：
  名称：

  A small molecule inhibitor selective for a variant ATP-binding site of the chaperonin GroEL

  摘要：

  The chaperonin GroEL is a megadalton-sized molecular machine that plays an essential role in the bacterial cell assisting protein folding to the native state through actions requiring ATP binding and hydrolysis. A combination of medicinal chemistry and genetics has been employed to generate an orthogonal pair, a small molecule that selectively inhibits ATPase activity of a GroEL ATP-binding pocket variant. An initial screen of kinase-directed inhibitors identified an active pyrazolo-pyrimidine scaffold that was iteratively modified and screened against a collective of GroEL nucleotide pocket variants to identify a cyclopentyl carboxamide derivative, EC3016, that specifically inhibits ATPase activity and protein folding by the GroEL mutant, I493C, involving a side chain positioned near the base of ATP. This orthogonal pair will enable in vitro studies of the action of ATP in triggering activation of GroEL-mediated protein folding and might enable further studies of GroEL action in vivo. The approach originated for studying kinases by Shokat and his colleagues may thus also be used to study large macromolecular machines. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.12.015
• 作为产物：
  描述：

  AB061 、 环戊基甲酰氯 在 吡啶 作用下， 以 氯仿 为溶剂， 生成 EC3016
  参考文献：
  名称：

  A small molecule inhibitor selective for a variant ATP-binding site of the chaperonin GroEL

  摘要：

  The chaperonin GroEL is a megadalton-sized molecular machine that plays an essential role in the bacterial cell assisting protein folding to the native state through actions requiring ATP binding and hydrolysis. A combination of medicinal chemistry and genetics has been employed to generate an orthogonal pair, a small molecule that selectively inhibits ATPase activity of a GroEL ATP-binding pocket variant. An initial screen of kinase-directed inhibitors identified an active pyrazolo-pyrimidine scaffold that was iteratively modified and screened against a collective of GroEL nucleotide pocket variants to identify a cyclopentyl carboxamide derivative, EC3016, that specifically inhibits ATPase activity and protein folding by the GroEL mutant, I493C, involving a side chain positioned near the base of ATP. This orthogonal pair will enable in vitro studies of the action of ATP in triggering activation of GroEL-mediated protein folding and might enable further studies of GroEL action in vivo. The approach originated for studying kinases by Shokat and his colleagues may thus also be used to study large macromolecular machines. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.12.015

文献信息

• [EN] COMPOSITIONS AND METHODS FOR TREATING TOXOPLASMOSIS. CRYPTOSPORIDIOSIS AND OTHER APICOMPLEXAN PROTOZOAN RELATED DISEASES<br/>[FR] COMPOSITIONS ET PROCÉDÉS POUR TRAITER LA TOXOPLASMOSE, LA CRYPTOSPORIDIOSE ET D'AUTRES MALADIES ASSOCIÉES AUX PROTOZOAIRES APICOMPLEXA
  申请人：UNIV WASHINGTON

  公开号：WO2011094628A1

  公开（公告）日：2011-08-04

  Compositions and methods for the treatment of toxoplasmosis-, caused by the infectious eukaryotic parasite Toxoplasma gondii (T, gondii) and for the treatment of ciyptosporidiosis, caused by the infectious eukaryotic parasites Cryptosporidium parvum (C parvuai) and Cnγtosporidium homimus (C. hominus) are described. In particular, the present disclosure is directed to compositions and methods for inhibiting either T. gondii calcium dependent protein kinases (TgCDPKs) or C. parvum and C. hominus calcium dependent protein kinases (CpDPKS) using pyrazolopyriinidine and/or imidazo[l,5-a]pyraziαe inhibitors, of the formula.(I), wherein the variables X. Y, Z, L. R1. and R3 are defined herein.

  本文描述了用于治疗由感染性真核寄生虫弓形虫（T. gondii）引起的弓形虫病和用于治疗由感染性真核寄生虫隐孢子虫（C. parvum）和人隐孢子虫（C. hominus）引起的隐孢子虫病的组合物和方法。具体而言，本公开涉及使用吡唑吡啶啉和/或咪唑[1,5-a]吡嗪类抑制剂来抑制T. gondii钙依赖蛋白激酶（TgCDPKs）或C. parvum和C. hominus钙依赖蛋白激酶（CpDPKS）的组合物和方法，其化学式为(I)，其中变量X、Y、Z、L、R1和R3在此处定义。
• Compositions and methods for treating toxoplasmosis, cryptosporidiosis, and other apicomplexan protozoan related diseases
  申请人：University of Washington through its Center for Commercialization

  公开号：US10544104B2

  公开（公告）日：2020-01-28

  Compositions and methods for the treatment of toxoplasmosis, caused by the infectious eukaryotic parasite Toxoplasma gondii (T. gondii) and for the treatment of cryptosporidiosis, caused by the infectious eukaryotic parasites Cryptosporidium parvum (C. parvum) and Cryptosporidium hominus (C. hominus) are described. In particular, the present disclosure is directed to compositions and methods for inhibiting either T. gondii calcium dependent protein kinases (TgCDPKs) or C. parvum and C. hominus calcium dependent protein kinases (CpCDPKs) using pyrazolopyrimidine and/or imidazo[1,5-a]pyrazine inhibitors, of the formula, wherein the variables X, Y, Z, L, R1, and R3 are defined herein.

  本发明描述了治疗由传染性真核寄生虫弓形虫（T. gondii）引起的弓形虫病和治疗由传染性真核寄生虫副隐孢子虫（C. parvum）和原隐孢子虫（C. hominus）引起的隐孢子虫病的组合物和方法。特别是，本公开涉及使用式中的吡唑嘧啶和/或咪唑并[1,5-a]吡嗪抑制剂抑制刚地隐孢子虫钙依赖性蛋白激酶（TgCDPKs）或副隐孢子虫和人隐孢子虫钙依赖性蛋白激酶（CpCDPKs）的组合物和方法、 其中变量 X、Y、Z、L、R1 和 R3 在本文中定义。
• COMPOSITIONS AND METHODS FOR TREATING TOXOPLASMOSIS. CRYPTOSPORIDIOSIS AND OTHER APICOMPLEXAN PROTOZOAN RELATED DISEASES
  申请人：University of Washington

  公开号：EP2528919B1

  公开（公告）日：2016-11-02
• Compositions And Methods For Treating Toxoplasmosis, Cryptosporidiosis, And Other Apicomplexan Protozoan Related Diseases
  申请人：VAN VOORHIS Wesley C.

  公开号：US20130018040A1

  公开（公告）日：2013-01-17

  Compositions and methods for the treatment of toxoplasmosis, caused by the infectious eukaryotic parasite Toxoplasma gondii ( T. gondii ) and for the treatment of cryptosporidiosis, caused by the infectious eukaryotic parasites Cryptosporidium parvum ( C. parvum ) and Cryptosporidium hominus ( C. hominus ) are described. In particular, the present disclosure is directed to compositions and methods for inhibiting either T. gondii calcium dependent protein kinases (TgCDPKs) or C. parvum and C. hominus calcium dependent protein kinases (CpCDPKs) using pyrazolopyrimidine and/or imidazo[1,5-a]pyrazine inhibitors, of the formula, wherein the variables X, Y, Z, L, R 1 , and R 3 are defined herein.
• Compositions and Methods for Treating Toxoplasmosis, Cryptosporidiosis, and Other Apicomplexan Protozoan Related Diseases
  申请人：University of Washington through its Center for Commercialization

  公开号：US20180022709A1

  公开（公告）日：2018-01-25

  Compositions and methods for the treatment of toxoplasmosis, caused by the infectious eukaryotic parasite Toxoplasma gondii ( T. gondii ) and for the treatment of cryptosporidiosis, caused by the infectious eukaryotic parasites Cryptosporidium parvum ( C. parvum ) and Cryptosporidium hominus ( C. hominus ) are described. In particular, the present disclosure is directed to compositions and methods for inhibiting either T. gondii calcium dependent protein kinases (TgCDPKs) or C. parvum and C. hominus calcium dependent protein kinases (CpCDPKs) using pyrazolopyrimidine and/or imidazo[1,5-a]pyrazine inhibitors, of the formula, wherein the variables X, Y, Z, L, R 1 , and R 3 are defined herein.