4-amino-7-(3-hydroxypropyl)-5-p-tolyl-7H-pyrrolo[2,3-d]pyrimidine-6-carbaldehyde

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 4-amino-7-(3-hydroxypropyl)-5-p-tolyl-7H-pyrrolo[2,3-d]pyrimidine-6-carbaldehyde
• 英文别名: 4-Amino-7-(3-hydroxypropyl)-5-(4-methylphenyl)pyrrolo[2,3-d]pyrimidine-6-carbaldehyde；4-amino-7-(3-hydroxypropyl)-5-(4-methylphenyl)pyrrolo[2,3-d]pyrimidine-6-carbaldehyde
• 化学式: C₁₇H₁₈N₄O₂
• 分子量: 310.356
• InChiKey: SNHIOHDMQAQUOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  94
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-amino-7-(3-hydroxypropyl)-5-p-tolyl-7H-pyrrolo[2,3-d]pyrimidine-6-carbaldehyde 、 N-氰乙酰基吗啡啉 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以21%的产率得到3-(4-amino-7-(3-hydroxypropyl)-5-p-tolyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-2-(morpholine-4-carbonyl)acrylonitrile
  参考文献：
  名称：

  KINASE INHIBITORS

  摘要：

  使用具有烯烃基团的激酶抑制剂抑制激酶的方法被披露。

  公开号：

  US20130035325A1
• 作为产物：
  描述：

  4-di-tert-butyloxycarbonylamino-7-(3-tert-butyldimethylsiloxypropyl)-5-p-tolyl-7H-pyrrolo[2,3-d]pyrimidine-6-carbaldehyde 在 三氟乙酸 、 盐酸 作用下， 以 二氯甲烷 、 四氢呋喃 、 水 为溶剂， 反应 36.0h， 以0.99 g的产率得到4-amino-7-(3-hydroxypropyl)-5-p-tolyl-7H-pyrrolo[2,3-d]pyrimidine-6-carbaldehyde
  参考文献：
  名称：

  KINASE INHIBITORS

  摘要：

  使用具有烯烃基团的激酶抑制剂抑制激酶的方法被披露。

  公开号：

  US20130035325A1

文献信息

• Design of Reversible, Cysteine-Targeted Michael Acceptors Guided by Kinetic and Computational Analysis
  作者：Shyam Krishnan、Rand M. Miller、Boxue Tian、R. Dyche Mullins、Matthew P. Jacobson、Jack Taunton

  DOI：10.1021/ja505194w

  日期：2014.9.10

  that covalently modify a cysteine thiol often show enhanced pharmacological potency and selectivity. Although reversible Michael acceptors have been reported, the structural requirements for reversibility are poorly understood. Here, we report a novel class of acrylonitrile-based Michael acceptors, activated by aryl or heteroaryl electron-withdrawing groups. We demonstrate that thiol adducts of these acrylonitriles

  共价修饰半胱氨酸硫醇的亲电探针通常表现出增强的药理学效力和选择性。尽管已经报道了可逆迈克尔受体，但对可逆性的结构要求知之甚少。在这里，我们报告了一类新的基于丙烯腈的迈克尔受体，由芳基或杂芳基吸电子基团激活。我们证明这些丙烯腈的硫醇加合物以超过 3 个数量级的速率进行 β-消除。这些速率与计算出的相应碳负离子的质子亲和力成反比，从而能够以可预测的方式调整硫醇-迈克尔反应的内在可逆性。我们将这些原理应用于设计具有改进特性的新型可逆共价激酶抑制剂。一种此类抑制剂的共晶结构揭示了 1,2,4-三唑激活基团与激酶之间的特定非共价相互作用。我们的实验和计算研究能够设计新的迈克尔受体，扩展可逆的、半胱氨酸靶向的亲电子试剂的调色板。
• Selective serine/threonine kinase inhibitors
  申请人：Taunton Jack

  公开号：US20070082884A1

  公开（公告）日：2007-04-12

  Inhibition of protein kinases having one or more cysteine residues within the ATP binding site is effected by contacting the kinase, per se or in a cell or subject, with an inhibitory-effective amount of a compound having a heterocyclic core structure comprised of two or more fused rings containing at least one nitrogen ring atom, and an electrophilic substituent that is capable of reacting with a cysteine residue within the ATP binding site of a kinase. Preferred compounds include certain pyrrolopyrimidines and oxindoles having such an electrophilic substituent and optionally an aromatic or heteroaromatic substituent that is capable of interacting with a threonine or smaller residue located in the gatekeeper position of the kinase. Kinases lacking such cysteine residues may be engineered or modified so that they are capable of being inhibited by such compounds by replacing a valine or other amino acid residue within the ATP binding site by a cysteine residue.
• SELECTIVE SERINE/THREONINE KINASE INHIBITORS
  申请人：Taunton Jack

  公开号：US20090221614A1

  公开（公告）日：2009-09-03

  Inhibition of protein kinases having one or more cysteine residues within the ATP binding site is effected by contacting the kinase, per se or in a cell or subject, with an inhibitory-effective amount of a compound having a heterocyclic core structure comprised of two or more fused rings containing at least one nitrogen ring atom, and an electrophilic substituent that is capable of reacting with a cysteine residue within the ATP binding site of a kinase. Preferred compounds include certain pyrrolopyrimidines and oxindoles having such an electrophilic substituent and optionally an aromatic or heteroaromatic substituent that is capable of interacting with a threonine or smaller residue located in the gatekeeper position of the kinase. Kinases lacking such cysteine residues may be engineered or modified so that they are capable of being inhibited by such compounds by replacing a valine or other amino acid residue within the ATP binding site by a cysteine residue.
• US8748601B2
  申请人：——

  公开号：US8748601B2

  公开（公告）日：2014-06-10
• US9505766B2
  申请人：——

  公开号：US9505766B2

  公开（公告）日：2016-11-29