N6-cyclohexyl-N2-(2-methoxy-4-piperazin-1-yl-phenyl)-9H-purine-2,6-diamine | 1246532-95-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N6-cyclohexyl-N2-(2-methoxy-4-piperazin-1-yl-phenyl)-9H-purine-2,6-diamine
• 英文别名: 6-N-cyclohexyl-2-N-(2-methoxy-4-piperazin-1-ylphenyl)-7H-purine-2,6-diamine
• CAS: 1246532-95-5
• 化学式: C₂₂H₃₀N₈O
• 分子量: 422.533
• InChiKey: XVUZUKSPGICVCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  103
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N6-cyclohexyl-N2-(2-methoxy-4-piperazin-1-yl-phenyl)-9H-purine-2,6-diamine 在 lithium aluminium tetrahydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 N6-cyclohexyl-N2-{2-methoxy-4-[4-(tetrahydrofuran-3-ylmethyl)piperazin-1-yl]phenyl}-9H-purine-2,6-diamine
  参考文献：
  名称：

  Lead optimization of purine based orally bioavailable Mps1 (TTK) inhibitors

  摘要：

  Efforts to optimize biological activity, novelty, selectivity and oral bioavailability of Mps1 inhibitors, from a purine based lead MPI-0479605, are described in this Letter. Mps1 biochemical activity and cytotoxicity in HCT-116 cell line were improved. On-target activity confirmation via mechanism based G2/M escape assay was demonstrated. Physico-chemical and ADME properties were optimized to improve oral bioavailability in mouse. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.131
• 作为产物：
  描述：

  2-chloro-N-cyclohexyl-9H-purin-6-amine 在 盐酸 、 palladium diacetate 、 caesium carbonate 、 对甲苯磺酸 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 甲苯 为溶剂， 生成 N6-cyclohexyl-N2-(2-methoxy-4-piperazin-1-yl-phenyl)-9H-purine-2,6-diamine
  参考文献：
  名称：

  Lead optimization of purine based orally bioavailable Mps1 (TTK) inhibitors

  摘要：

  Efforts to optimize biological activity, novelty, selectivity and oral bioavailability of Mps1 inhibitors, from a purine based lead MPI-0479605, are described in this Letter. Mps1 biochemical activity and cytotoxicity in HCT-116 cell line were improved. On-target activity confirmation via mechanism based G2/M escape assay was demonstrated. Physico-chemical and ADME properties were optimized to improve oral bioavailability in mouse. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.131

文献信息

• COMPOUNDS AND THERAPEUTIC USES THEREOF
  申请人：Kumar Dange Vijay

  公开号：US20120122840A1

  公开（公告）日：2012-05-17

  The invention relates to compounds, pharmaceutical compositions, and uses thereof, including therapeutic uses thereof, such as methods useful for treating cancer.

  本发明涉及化合物、药物组合物及其用途，包括治疗用途，例如用于治疗癌症的有用方法。
• [EN] PURINE DERIVATIVES USEFUL AS ANTI - CANCER AGENTS<br/>[FR] COMPOSÉS ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：MYRIAD PHARMACEUTICALS INC

  公开号：WO2010111406A3

  公开（公告）日：2011-07-07
• [EN] COMPOUNDS AND THERAPEUTIC USES THEREOF<br/>[FR] COMPOSÉS ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：MYRIAD PHARMACEUTICALS INC

  公开号：WO2010111406A2

  公开（公告）日：2010-09-30

  The invention relates to compounds of formulae I or II, pharmaceutical compositions, and uses thereof, including therapeutic uses thereof, such as methods useful for treating cancer.
• Lead optimization of purine based orally bioavailable Mps1 (TTK) inhibitors
  作者：D. Vijay Kumar、Christophe Hoarau、Matthew Bursavich、Paul Slattum、David Gerrish、Kraig Yager、Michael Saunders、Mark Shenderovich、Bruce L. Roth、Rena McKinnon、Ashley Chan、Daniel M. Cimbora、Chad Bradford、Leslie Reeves、Scott Patton、Damon I. Papac、Brandi L. Williams、Robert O. Carlson

  DOI：10.1016/j.bmcl.2012.04.131

  日期：2012.7

  Efforts to optimize biological activity, novelty, selectivity and oral bioavailability of Mps1 inhibitors, from a purine based lead MPI-0479605, are described in this Letter. Mps1 biochemical activity and cytotoxicity in HCT-116 cell line were improved. On-target activity confirmation via mechanism based G2/M escape assay was demonstrated. Physico-chemical and ADME properties were optimized to improve oral bioavailability in mouse. (C) 2012 Elsevier Ltd. All rights reserved.