N-(1-isobutoxyethoxy)-2-(6-{[(naphthalen-2-ylmethyl)amino]methyl}-3-azabicyclo[3.1.0]hex-3-yl)pyrimidine-5-carboxamide. | 914938-29-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-(1-isobutoxyethoxy)-2-(6-{[(naphthalen-2-ylmethyl)amino]methyl}-3-azabicyclo[3.1.0]hex-3-yl)pyrimidine-5-carboxamide.
• 英文别名: N-(1-isobutoxyethoxy) 2-(6-{[(naphthalen-2-ylmethyl)amino]methyl}-3-azabicyclo[3.1.0]hex-3-yl)pyrimidine-5-carboxamide；N-[1-(2-methylpropoxy)ethoxy]-2-[6-[(naphthalen-2-ylmethylamino)methyl]-3-azabicyclo[3.1.0]hexan-3-yl]pyrimidine-5-carboxamide
• CAS: 914938-29-7
• 化学式: C₂₈H₃₅N₅O₃
• 分子量: 489.618
• InChiKey: YFADIUIPHORDKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  88.6
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(1-isobutoxyethoxy)-2-(6-{[(naphthalen-2-ylmethyl)amino]methyl}-3-azabicyclo[3.1.0]hex-3-yl)pyrimidine-5-carboxamide. 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 0.17h， 以50%的产率得到N-hydroxy-2-{6-[(naphthalen-2-ylmethylamino)methyl]-3-azabicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide
  参考文献：
  名称：

  WO2006/123121

  摘要：

  公开号：
• 作为产物：
  描述：

  2-甲砜基-5-嘧啶甲酸乙酯 在 盐酸 、 甲醇 、 水 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 97.34h， 生成 N-(1-isobutoxyethoxy)-2-(6-{[(naphthalen-2-ylmethyl)amino]methyl}-3-azabicyclo[3.1.0]hex-3-yl)pyrimidine-5-carboxamide.
  参考文献：
  名称：

  Discovery of 2-(6-{[(6-Fluoroquinolin-2-yl)methyl]amino}bicyclo[3.1.0]hex-3-yl)-N-hydroxypyrimidine-5-carboxamide (CHR-3996), a Class I Selective Orally Active Histone Deacetylase Inhibitor

  摘要：

  A novel series of HDAC inhibitors demonstrating class I subtype selectivity and good oral bioavailability is described. The compounds are potent enzyme inhibitors (IC50 values less than 100 nM), and improved activity in cell proliferation assays was achieved by modulation of polar surface area (PSA) through the introduction of novel linking groups. Employing oral pharmacokinetic studies in mice, comparing drug levels in spleen to plasma, we selected compounds that were tested for efficacy in human tumor xenograft studies based on their potential to distribute into tumor. One compound, 21r (CHR-3996), showed good oral activity in these models, including dose-related activity in a LoVo xenograft. In addition 21r showed good activity in combination with other anticancer agents in in vitro studies. On the basis of these results, 21r was nominated for clinical development.

  DOI：

  10.1021/jm101177s

文献信息

• Histone Deacetylase Inhibitors
  申请人：Moffat David Festus Charles

  公开号：US20100152155A1

  公开（公告）日：2010-06-17

  Compounds of formula: (I), and salts, N-oxides, hydrates and solvates thereof are histone deacetylase inhibitors and are useful in the treatment of cell proliferative diseases, including cancers: (I) wherein Q, V and W independently represent —N═ or —C═; B is a divalent radical selected from: (IIA), (IIB), (IIC), (IID), and (IIE). Wherein the bond marked * is linked to the ring containing Q, V and W through -[Linker1]- and the bond marked ** is linked to A through -[Linker2]-; A is an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system; and -[Linker1]- and -[Linker2]- independently represent a bond, or a divalent linker radical.

  式为(I)的化合物、盐、N-氧化物、水合物和溶剂化物均为组蛋白去乙酰化酶抑制剂，可用于治疗细胞增殖性疾病，包括癌症：(I)其中Q、V和W分别代表—N═或—C═；B是从(IIA)、(IIB)、(IIC)、(IID)和(IIE)中选择的二价基团。其中标记为*的键通过-[连接1]-与含有Q、V和W的环相连，标记为**的键通过-[连接2]-与A相连；A是一个可选取代的单环、双环或三环碳环或杂环系统；-[连接1]-和-[连接2]-分别表示键或二价连接基团。
• Histone deacetylase inhibitors
  申请人：Chroma Therapeutics Ltd.

  公开号：US07932246B2

  公开（公告）日：2011-04-26

  Compounds of formula: (I), and salts, N-oxides, hydrates and solvates thereof are histone deacetylase inhibitors and are useful in the treatment of cell proliferative diseases, including cancers: (I) wherein Q, V and W independently represent —N═ or —C═; B is a divalent radical selected from: (IIA), (IIB), (IIC), (IID), and (IIE). Wherein the bond marked * is linked to the ring containing Q, V and W through -[Linker1]- and the bond marked ** is linked to A through -[Linker2]-; A is an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system; and -[Linker1]- and -[Linker2]- independently represent a bond, or a divalent linker radical.

  公式为（I）的化合物及其盐、N-氧化物、水合物和溶剂化合物是组蛋白去乙酰化酶抑制剂，可用于治疗细胞增殖性疾病，包括癌症：其中Q、V和W分别表示—N═或—C═；B是从（IIA）、（IIB）、（IIC）、（IID）和（IIE）中选择的二价基团。其中标有*的键通过-[Linker1]-与含有Q、V和W的环相连，标有**的键通过-[Linker2]-与A相连；A是可选取代的单环、双环或三环碳环或杂环系统；-[Linker1]-和-[Linker2]-分别表示键或二价连接基团。
• WO2006/123121
  申请人：——

  公开号：——

  公开（公告）日：——
• HISTONE DEACETYLASE INHIBITORS
  申请人：Chroma Therapeutics Limited

  公开号：EP1881977A1

  公开（公告）日：2008-01-30
• US7932246B2
  申请人：——

  公开号：US7932246B2

  公开（公告）日：2011-04-26