(azithromycin-3'-(N-(2-triazolylbenzyl)))-N-hydroxyheptanamide

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (azithromycin-3'-(N-(2-triazolylbenzyl)))-N-hydroxyheptanamide
• 英文别名: 7-[4-[2-[[[(2S,3R,4S,6R)-2-[[(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-2-ethyl-3,4,10-trihydroxy-13-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,6,8,10,12,14-heptamethyl-15-oxo-1-oxa-6-azacyclopentadec-11-yl]oxy]-3-hydroxy-6-methyloxan-4-yl]-methylamino]methyl]phenyl]triazol-1-yl]-N-hydroxyheptanamide
• 化学式: C₅₃H₉₀N₆O₁₄
• 分子量: 1035.33
• InChiKey: AQJOBVFCYXDUFA-GGXWVIOLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  73
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  260
• 氢给体数：
  7
• 氢受体数：
  18

反应信息

• 作为产物：
  描述：

  7-叠氮庚酸 在 copper(l) iodide 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 cesium fluoride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 12.25h， 生成 (azithromycin-3'-(N-(2-triazolylbenzyl)))-N-hydroxyheptanamide
  参考文献：
  名称：

  A structure–activity relationship of non-peptide macrocyclic histone deacetylase inhibitors and their anti-proliferative and anti-inflammatory activities

  摘要：

  Inhibition of the enzymatic activity of histone deacetylase (HDAC) is a promising therapeutic strategy for cancer treatment and several distinct small molecule histone deacetylase inhibitors (HDACi) have been reported. We have previously identified a new class of non-peptide macrocyclic HDACi derived from 14- and 15-membered macrolide skeletons. In these HDACi, the macrocyclic ring is linked to the zinc chelating hydroxamate moiety through a para-substituted aryl-triazole cap group. To further delineate the depth of the SAR of this class of HDACi, we have synthesized series of analogous compounds and investigated the influence of various substitution patterns on their HDAC inhibitory, anti-proliferative and anti-inflammatory activities. We identified compounds 25b and 38f with robust anti-proliferative activities and compound 26f (IC50 47.2 nM) with superior anti-inflammatory (IC50 88 nM) activity relative to SAHA. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.10.045

文献信息

• 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。
• US8871728B2
  申请人：——

  公开号：US8871728B2

  公开（公告）日：2014-10-28
• A structure–activity relationship of non-peptide macrocyclic histone deacetylase inhibitors and their anti-proliferative and anti-inflammatory activities
  作者：Subhasish Tapadar、Shaghayegh Fathi、Idris Raji、Wilson Omesiete、James R. Kornacki、Sandra C. Mwakwari、Masanori Miyata、Kazunori Mitsutake、Jian-Dong Li、Milan Mrksich、Adegboyega K. Oyelere

  DOI：10.1016/j.bmc.2015.10.045

  日期：2015.12

  Inhibition of the enzymatic activity of histone deacetylase (HDAC) is a promising therapeutic strategy for cancer treatment and several distinct small molecule histone deacetylase inhibitors (HDACi) have been reported. We have previously identified a new class of non-peptide macrocyclic HDACi derived from 14- and 15-membered macrolide skeletons. In these HDACi, the macrocyclic ring is linked to the zinc chelating hydroxamate moiety through a para-substituted aryl-triazole cap group. To further delineate the depth of the SAR of this class of HDACi, we have synthesized series of analogous compounds and investigated the influence of various substitution patterns on their HDAC inhibitory, anti-proliferative and anti-inflammatory activities. We identified compounds 25b and 38f with robust anti-proliferative activities and compound 26f (IC50 47.2 nM) with superior anti-inflammatory (IC50 88 nM) activity relative to SAHA. (C) 2015 Elsevier Ltd. All rights reserved.