methyl(7R)-7-amino-5,6,7,8-tetrahydronaphthalene-2-carboxylate hydrochloride | 1355592-62-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: methyl(7R)-7-amino-5,6,7,8-tetrahydronaphthalene-2-carboxylate hydrochloride
• 英文别名: methyl (7R)-7-amino-5,6,7,8-tetrahydronaphthalene-2-carboxylate;hydrochloride
• CAS: 1355592-62-9
• 化学式: C₁₂H₁₅NO₂*ClH
• 分子量: 241.718
• InChiKey: FBNUPRHUWHXNMG-RFVHGSKJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.71
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  52.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl(7R)-7-amino-5,6,7,8-tetrahydronaphthalene-2-carboxylate hydrochloride 在 羟胺 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 (3R)-3-[[4-(3-pyridyl)pyrimidin-2-yl]amino]tetralin-6-carbohydroxamic acid
  参考文献：
  名称：

  Identification of a Novel Aminotetralin Class of HDAC6 and HDAC8 Selective Inhibitors

  摘要：

  Herein we report the identification of a novel class of HDAC6 and HDAC8 selective inhibitors through a unique chemistry and phenotypic screening startegy. Tetrahy droisoquinoline 12 was identified as a potent HDAC6 and HDAC8 dual inhibitor from a focussed library through cellular tubulin acetylation and p21 induction screening assays. Scaffold hopping from 12 led to the discovery of an aminotetralin class of HDAC inhibitors. In particular, the 3-R stereoisomeer 32 showed highly potent inhibiton agains HDAC6 and HDAC6 and HDAC8 with IC50 values of 50 and 80 nM, respectively. Treatment of neuroblastoma BE(2) C cells with 32 resulted in elevated levels of acetylated tubulin, TrKA, and neurite outgrowth with only marginal effects on p21 induction and histone H3 acetylation Consistent withits weak enzymatic indhibition of HDAC, showed significantly less cytotoxicity than SAHA and moderately inhibited the growth of myeloma NCI-H929 and OPM-2 cells.

  DOI：

  10.1021/jm5008962
• 作为产物：
  描述：

  7-溴-3,4-二氢-1H-2-萘酮 在 盐酸 、 甲醇 、 1,3-双(二苯基膦)丙烷 、 ammonium acetate 、 palladium diacetate 、 sodium cyanoborohydride 、 三乙胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 16.0h， 生成 methyl(7R)-7-amino-5,6,7,8-tetrahydronaphthalene-2-carboxylate hydrochloride
  参考文献：
  名称：

  Identification of a Novel Aminotetralin Class of HDAC6 and HDAC8 Selective Inhibitors

  摘要：

  Herein we report the identification of a novel class of HDAC6 and HDAC8 selective inhibitors through a unique chemistry and phenotypic screening startegy. Tetrahy droisoquinoline 12 was identified as a potent HDAC6 and HDAC8 dual inhibitor from a focussed library through cellular tubulin acetylation and p21 induction screening assays. Scaffold hopping from 12 led to the discovery of an aminotetralin class of HDAC inhibitors. In particular, the 3-R stereoisomeer 32 showed highly potent inhibiton agains HDAC6 and HDAC6 and HDAC8 with IC50 values of 50 and 80 nM, respectively. Treatment of neuroblastoma BE(2) C cells with 32 resulted in elevated levels of acetylated tubulin, TrKA, and neurite outgrowth with only marginal effects on p21 induction and histone H3 acetylation Consistent withits weak enzymatic indhibition of HDAC, showed significantly less cytotoxicity than SAHA and moderately inhibited the growth of myeloma NCI-H929 and OPM-2 cells.

  DOI：

  10.1021/jm5008962

文献信息

• SUBSTITUTED HYDROXAMIC ACIDS AND USES THEREOF
  申请人：Blackburn Christopher

  公开号：US20120015943A1

  公开（公告）日：2012-01-19

  This invention provides compounds of formula (I): wherein R 1 , R 1b , R 2a , R 2b , R 2c , and R 2d have values as described in the specification, useful as inhibitors of HDAC6. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of proliferative, inflammatory, infectious, neurological or cardiovascular diseases or disorders.

  本发明提供了公式(I)的化合物： 其中R1、R1b、R2a、R2b、R2c和R2d的值如说明书中所述，可用作HDAC6的抑制剂。本发明还提供了包含本发明化合物的药物组合物，以及使用这些组合物治疗增殖性、炎症性、感染性、神经性或心血管疾病或失调的方法。
• Identification of a Novel Aminotetralin Class of HDAC6 and HDAC8 Selective Inhibitors
  作者：Guozhi Tang、Jason C. Wong、Weixing Zhang、Zhanguo Wang、Nan Zhang、Zhenghong Peng、Zhenshan Zhang、Yiping Rong、Shijie Li、Meifang Zhang、Lingjie Yu、Teng Feng、Xiongwen Zhang、Xihan Wu、Jim Z. Wu、Li Chen

  DOI：10.1021/jm5008962

  日期：2014.10.9

  Herein we report the identification of a novel class of HDAC6 and HDAC8 selective inhibitors through a unique chemistry and phenotypic screening startegy. Tetrahy droisoquinoline 12 was identified as a potent HDAC6 and HDAC8 dual inhibitor from a focussed library through cellular tubulin acetylation and p21 induction screening assays. Scaffold hopping from 12 led to the discovery of an aminotetralin class of HDAC inhibitors. In particular, the 3-R stereoisomeer 32 showed highly potent inhibiton agains HDAC6 and HDAC6 and HDAC8 with IC50 values of 50 and 80 nM, respectively. Treatment of neuroblastoma BE(2) C cells with 32 resulted in elevated levels of acetylated tubulin, TrKA, and neurite outgrowth with only marginal effects on p21 induction and histone H3 acetylation Consistent withits weak enzymatic indhibition of HDAC, showed significantly less cytotoxicity than SAHA and moderately inhibited the growth of myeloma NCI-H929 and OPM-2 cells.