methyl 8-((4-(hydroxymethyl)phenyl)amino)-8-oxooctanoate | 910610-24-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 8-((4-(hydroxymethyl)phenyl)amino)-8-oxooctanoate
• 英文别名: methyl 8-(4-(hydroxylmethyl)phenylamino)-8-oxo-octanoate；methyl 8-(4-(hydroxymethyl)phenylamino)-8-oxooctanoate；methyl 8-[4-(hydroxymethyl)anilino]-8-oxooctanoate
• CAS: 910610-24-1
• 化学式: C₁₆H₂₃NO₄
• 分子量: 293.363
• InChiKey: WYHWQIDYMOKGAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  21
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 8-((4-(hydroxymethyl)phenyl)amino)-8-oxooctanoate 在 pyridinium chlorochromate 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以95%的产率得到methyl 8-((4-formylphenyl)amino)-8-oxooctanoate
  参考文献：
  名称：

  发现新型多作用拓扑异构酶I / II和组蛋白脱乙酰基酶抑制剂

  摘要：

  设计多靶点药物仍然是当前抗肿瘤药物发现中的重大挑战。由于拓扑异构酶和HDAC抑制剂之间的协同作用，本研究报道了拓扑异构酶I / II和HDAC的同类中的三重抑制剂。在3-氨基-10-羟基乙二胺和SAHA的基础上，成功设计并合成了一系列杂化分子。特别是，化合物8c被证明是拓扑异构酶I / II和HDAC的有效抑制剂，具有良好的抗增殖和凋亡活性。这项概念验证研究还验证了发现三重拓扑异构酶I / II和HDAC抑制剂作为新型抗肿瘤药的有效性。

  DOI：

  10.1021/ml500327q
• 作为产物：
  描述：

  在 四丁基氟化铵 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.5h， 以275 mg的产率得到methyl 8-((4-(hydroxymethyl)phenyl)amino)-8-oxooctanoate
  参考文献：
  名称：

  Non-Peptide Macrocyclic Histone Deacetylase Inhibitors

  摘要：

  Inhibition of histone deacetylase inhibitors (HDACi) hold great promise in cancer therapy because of their demonstrated ability to arrest proliferation of nearly all transformed cell types. Of the several structurally distinct small molecule HDACi reported, macrocyclic depsipeptides have the most complex recognition cap-group moieties and present an excellent opportunity for the modulation of the biological activities of HDACi. Unfortunately, the structure-activity relationship (SAR) studies for this class of compounds have been impaired largely because most macrocyclic HDACi known to date comprise complex peptide macrocycles. In addition to retaining the pharmacologically disadvantaged peptidyl backbone, they offer only limited opportunity for side chain modifications. Here, we report the discovery of a new class of macrocyclic HDAG based on the macrolide antibiotics skeletons. SAR studies revealed that these compounds displayed both linker-length and macrolide-type dependent HDAC inhibition activities with IC50 in the low nanomolar range. In addition, these non-peptide macrocyclic HDACi are more selective against HDACs 1 and 2 relative to HDAC 8, another class I HDAC isoform, and hence have subclass HDAC isoform selectivity.

  DOI：

  10.1021/jm801128g

文献信息

• A New Approach to Tubacin
  作者：Jian Hong、Xin Xu、Debasis Das、Pengyu Yang、Shu-Hui Chen、Ge Li

  DOI：10.2174/157017810790533913

  日期：2010.1.1

  A new simple synthesis of tubacin is reported. It entails the formation of the syn-1,3-diol unit and its stereoselective ketalization with a functionalized benzaldehyde derivative.

  报道了一种新的简单合成 tubacin 的方法。该方法涉及 syn-1,3-二醇单元的形成及其与功能化苯甲醛衍生物的立体选择性缩醛化。
• Non-Peptide Macrocyclic Histone Deacetylase (HDAC) Inhibitors and Methods of Making and Using Thereof
  申请人：Oyelere Adegboyega

  公开号：US20100197622A1

  公开（公告）日：2010-08-05

  Compounds of Formula I or II, and methods of making and using thereof, are described herein. M represents a macrolide subunit, n is a C 1-6 group, optionally containing one or more heteroatoms, D is an alkyl or aryl group, A is a linking group connected to D, B is an alkyl, alkylaryl or alkylheteroaryl spacer group, ZBG is a Zinc Binding Group, R 1 , R 2 and R 4 are independently are selected from hydrogen, a C1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 1-6 alkanoate group, a C 2-6 carbamate group, a C 2-6 carbonate group, a C 2-6 carbamate group, or a C 2-6 thiocarbamate group, R 3 is hydrogen or —OR 5 , R 5 is selected from a group consisting of Hydrogen, a C 1-6 alkyl hgroup, a C 2-6 alkenyl group, a C 2-6 alkynyl group, C 1-6 alkanoate group, C 2-6 carbamate group, C 2-6 carbonate group, C 2-6 carbamate group, or C 2-6 thiocarbamate group.

  本文描述了公式I或II的化合物，以及制备和使用它们的方法。其中，M代表大环内酯亚基，n是C1-6基团，可选地含有一个或多个杂原子，D是烷基或芳基基团，A是连接到D的连接基团，B是烷基、烷基芳基或烷基杂芳基间隔基团，ZBG是锌结合基团，R1、R2和R4独立地选择自氢、C1-6烷基、C2-6烯基、C2-6炔基、C1-6烷酸酯基、C2-6氨基甲酸酯基、C2-6碳酸酯基、C2-6氨基甲酸酯基或C2-6硫代氨基甲酸酯基，R3是氢或-OR5，R5选择自氢、C1-6烷基、C2-6烯基、C2-6炔基、C1-6烷酸酯基、C2-6氨基甲酸酯基、C2-6碳酸酯基、C2-6氨基甲酸酯基或C2-6硫代氨基甲酸酯基的一组。
• Non-peptide macrocyclic histone deacetylase (HDAC) inhibitors and methods of making and using thereof
  申请人：Georgia Tech Research Corporation

  公开号：US08188054B2

  公开（公告）日：2012-05-29

  Compounds of Formula I or II, and methods of making and using thereof, are described herein. M represents a macrolide subunit, n is a C1-6 group, optionally containing one or more heteroatoms, D is an alkyl or aryl group, A is a linking group connected to D, B is an alkyl, alkylaryl or alkylheteroaryl spacer group, ZBG is a Zinc Binding Group, R1, R2 and R4 are independently are selected from hydrogen, a C1-6 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, a C1-6 alkanoate group, a C2-6 carbamate group, a C2-6 carbonate group, a C2-6 carbamate group, or a C2-6 thiocarbamate group, R3 is hydrogen or —OR5, R5 is selected from a group consisting of Hydrogen, a C1-6 alkyl hgroup, a C2-6 alkenyl group, a C2-6 alkynyl group, C1-6 alkanoate group, C2-6 carbamate group, C2-6 carbonate group, C2-6 carbamate group, or C2-6 thiocarbamate group.

  本文描述了I或II式化合物及其制备和使用方法。其中，M代表大环内酯亚基，n为C1-6基团，可选含有一个或多个杂原子，D为烷基或芳基基团，A为连接到D的连接基团，B为烷基、烷基芳基或烷基杂芳基间隔基团，ZBG为锌结合基团，R1、R2和R4独立地选择自氢、C1-6烷基、C2-6烯基、C2-6炔基、C1-6烷酸酯基、C2-6碳酸酯基、C2-6氨基甲酸酯基、C2-6硫代氨基甲酸酯基或C2-6硫代氨基甲酸酯基，R3为氢或—OR5，R5选择自氢、C1-6烷基、C2-6烯基、C2-6炔基、C1-6烷酸酯基、C2-6碳酸酯基、C2-6氨基甲酸酯基、C2-6硫代氨基甲酸酯基或C2-6硫代氨基甲酸酯基。
• NON-PEPTIDE MACROCYCLIC HISTONE DEACETYLASE (HDAC) INHIBITORS AND METHODS OF MAKING AND USING THEREOF
  申请人：Oyelere Adegboyega

  公开号：US20120329741A1

  公开（公告）日：2012-12-27

  Compounds of Formula I or II, and methods of making and using thereof, are described herein. M represents a macrolide subunit, E is a C 1-6 group, optionally containing one or more heteroatoms, D is an alkyl or aryl group, A is a linking group connected to D, B is an alkyl, alkylaryl or alkylheteroaryl spacer group, ZBG is a Zinc Binding Group, R 1 , R 2 and R 4 are independently are selected from hydrogen, a C1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 1-6 alkanoate group, a C 2-6 carbamate group, a C 2-6 carbonate group, a C 2-6 carbamate group, or a C 2-6 thiocarbamate group, R 3 is hydrogen or —OR 5 , R 5 is selected from a group consisting of Hydrogen, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, C 1-6 alkanoate group, C 2-6 carbamate group, C 2-6 carbonate group, C 2-6 carbamate group, or C 2-6 thiocarbamate group.

  本文描述了I或II式化合物及其制备和使用方法。其中，M代表大环内酯亚基，E为C1-6基团，可选含有一个或多个杂原子，D为烷基或芳基基团，A为连接到D的连接基团，B为烷基、烷基芳基或烷基杂芳基间隔基团，ZBG为锌结合基团，R1、R2和R4独立地选择自氢、C1-6烷基、C2-6烯基、C2-6炔基、C1-6烷酸酯基、C2-6氨基甲酸酯基、C2-6碳酸酯基、C2-6氨基甲酰基或C2-6硫代氨基甲酰基，R3为氢或-OR5，R5选择自氢、C1-6烷基、C2-6烯基、C2-6炔基、C1-6烷酸酯基、C2-6氨基甲酸酯基、C2-6碳酸酯基、C2-6氨基甲酰基或C2-6硫代氨基甲酰基。
• Non-peptide macrocyclic histone deacetylese (HDAC) inhibitors and methods of making and using thereof
  申请人：Oyelere Adegboyega

  公开号：US08871728B2

  公开（公告）日：2014-10-28

  Compounds of Formula I or II, and methods of making and using thereof, are described herein. M represents a macrolide subunit, E is a C1-6 group, optionally containing one or more heteroatoms, D is an alkyl or aryl group, A is a linking group connected to D, B is an alkyl, alkylaryl or alkylheteroaryl spacer group, ZBG is a Zinc Binding Group, R1, R2 and R4 are independently are selected from hydrogen, a C1-6 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, a C1-6 alkanoate group, a C2-6 carbamate group, a C2-6 carbonate group, a C2-6 carbamate group, or a C2-6 thiocarbamate group, R3 is hydrogen or —OR5, R5 is selected from a group consisting of Hydrogen, a C1-6 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, C1-6 alkanoate group, C2-6 carbamate group, C2-6 carbonate group, C2-6 carbamate group, or C2-6 thiocarbamate group.

  本文描述了化合物I或II的公式，以及制备和使用它们的方法。其中，M代表大环内酯亚基，E是C1-6基团，可以包含一个或多个杂原子，D是烷基或芳基基团，A是连接到D的连接基团，B是烷基、烷基芳基或烷基杂芳基间隔基团，ZBG是锌结合基团，R1、R2和R4分别选择自氢、C1-6烷基、C2-6烯基、C2-6炔基、C1-6烷酸酯基、C2-6氨基甲酸酯基、C2-6碳酸酯基、C2-6氨基甲酸酯基或C2-6硫代氨基甲酸酯基，R3是氢或—OR5，R5选择自氢、C1-6烷基、C2-6烯基、C2-6炔基、C1-6烷酸酯基、C2-6氨基甲酸酯基、C2-6碳酸酯基、C2-6氨基甲酸酯基或C2-6硫代氨基甲酸酯基。