AB058 | 1092789-31-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: AB058
• 英文别名: 1-tert-butyl-3-(3-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine；1-tert-butyl-3-(3-nitrophenyl)pyrazolo[3,4-d]pyrimidin-4-amine
• CAS: 1092789-31-5
• 化学式: C₁₅H₁₆N₆O₂
• 分子量: 312.331
• InChiKey: ZTMUNGPVTSWGLK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  115
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  AB058 在 palladium on activated charcoal 、 氢气 作用下， 以 乙醇 为溶剂， 生成 AB060
  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：

  、 formamide 生成 AB058
  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

• Kinase antagonists
  申请人：Knight A. Zachary

  公开号：US20070293516A1

  公开（公告）日：2007-12-20

  The present invention provides novel compounds that are antagonists of PI3 kinase, PI3 kinase and tryosine kinase, PI3Kinase and mTOR, or PI3Kinase, mTOR and tryosine kinase.

  本发明提供了一种新型化合物，它们是 PI3 激酶、PI3 激酶和酪氨酸激酶、PI3 激酶和 mTOR，或者 PI3 激酶、mTOR 和酪氨酸激酶的拮抗剂。
• KINASE ANTAGONISTS
  申请人：KNIGHT ZACHARY A.

  公开号：US20100009963A1

  公开（公告）日：2010-01-14

  The present invention provides novel compounds that are antagonists of PI3 kinase, PI3 kinase and tyrosine kinase, PI3 kinase and mTOR, or PI33 kinase, mTOR and tyrosine kinase.

  本发明提供了一些新型化合物，它们是PI3激酶、PI3激酶和酪氨酸激酶、PI3激酶和mTOR、或PI3激酶、mTOR和酪氨酸激酶的拮抗剂。
• Kinase Antagonists
  申请人：Knight Zachary A.

  公开号：US20110301144A1

  公开（公告）日：2011-12-08

  The present invention provides novel compounds that are antagonists of PI3 kinase, PI3 kinase and tyrosine kinase, PI3 kinase and mTOR, or PI33 kinase, mTOR and tyrosine kinase.

  本发明提供了一种新型化合物，它们是PI3激酶、PI3激酶和酪氨酸激酶、PI3激酶和mTOR或PI33激酶、mTOR和酪氨酸激酶的拮抗剂。
• Substituted pyrazolo[3,4-D]pyrimidines as kinase antagonists
  申请人：The Regents of the University of California

  公开号：US07585868B2

  公开（公告）日：2009-09-08

  The present invention provides novel compounds that can be used as antagonists of a lipid kinase such as a PI3 kinase, protein tyrosine kinase, and/or protein serine-threonine kinases such as mTOR. The present invention also provides methods of using the compounds for treating various disease conditions. The compounds include those having the formula: wherein the R1, R2 and R36 are as defined herein.

  本发明提供了一种新颖的化合物，可用作脂质激酶（如PI3激酶，蛋白酪氨酸激酶和/或蛋白丝氨酸/苏氨酸激酶，如mTOR）的拮抗剂。本发明还提供了使用这些化合物治疗各种疾病的方法。这些化合物包括具有以下式的化合物：其中R1，R2和R36如本文所定义。
• Substituted pyrazolo[3,2-d]pyrimidines as anti-cancer agents
  申请人：Knight Zachary A.

  公开号：US08642604B2

  公开（公告）日：2014-02-04

  The present invention provides novel compounds that are antagonists of PI3 kinase, PI3 kinase and tyrosine kinase, PI3 kinase and mTOR, or PI33 kinase, mTOR and tyrosine kinase.

  本发明提供了一种新型化合物，其为PI3激酶、PI3激酶和酪氨酸激酶、PI3激酶和mTOR或PI33激酶、mTOR和酪氨酸激酶的拮抗剂。