3-[[4-(3-pyridyl)pyrimidin-2-yl]amino]tetralin-6-carbohydroxamic acid | 1364164-61-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-[[4-(3-pyridyl)pyrimidin-2-yl]amino]tetralin-6-carbohydroxamic acid
• 英文别名: 7-(4-Pyridin-3-yl-pyrimidin-2-ylamino)-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid hydroxyamide；7-(4-pyridin-3-ylpyrimidin-2-ylamino)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid hydroxyamide；N-hydroxy-7-[(4-pyridin-3-ylpyrimidin-2-yl)amino]-5,6,7,8-tetrahydronaphthalene-2-carboxamide
• CAS: 1364164-61-3
• 化学式: C₂₀H₁₉N₅O₂
• 分子量: 361.403
• InChiKey: MWLFQRZKKHIDTM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  100
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 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 、 羟胺 、 palladium diacetate 、 sodium cyanoborohydride 、 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 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

文献信息

• NOVEL N-HYDROXY-BENZAMIDS FOR THE TREATMENT OF CANCER
  申请人：Guo Lei

  公开号：US20120065204A1

  公开（公告）日：2012-03-15

  The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt, ester or stereoisomer thereof, wherein R 1 to R 3 and X have the significances given herein. The present invention is also directed to processes for making said compounds and uses of said compounds, in particular their use as medicaments, more particularly their use as medicaments in the treatment of cancer.

  本发明提供了式（I）的化合物或其药学上可接受的盐、酯或立体异构体，其中R1至R3和X具有本文中给出的含义。本发明还涉及制备所述化合物的方法和所述化合物的用途，特别是它们作为药物的用途，更具体地说是它们作为治疗癌症的药物的用途。
• [EN] NOVEL N-HYDROXY-BENZAMIDES FOR THE TREATMENT OF CANCER<br/>[FR] NOUVEAUX N-HYDROXY-BENZAMIDES DESTINÉS AU TRAITEMENT DU CANCER
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012031993A1

  公开（公告）日：2012-03-15

  The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt, ester or stereoisomer thereof, wherein R1 to R3 and X have the significances given herein. The present invention is also directed to processes for making said compounds and uses of said compounds, in particular their use as medicaments, more particularly their use as medicaments in the treatment of cancer.

  本发明提供了式（I）的化合物或其药用可接受的盐、酯或立体异构体，其中R1至R3和X具有本文中给出的含义。本发明还涉及制备所述化合物的方法和所述化合物的用途，特别是它们作为药物的用途，更具体地说是它们作为治疗癌症的药物的用途。
• NOVEL N-HYDROXY-BENZAMIDES FOR THE TREATMENT OF CANCER
  申请人：F.Hoffmann-La Roche AG

  公开号：EP2613775A1

  公开（公告）日：2013-07-17
• N-HYDROXY-BENZAMIDES FOR THE TREATMENT OF CANCER
  申请人：F.Hoffmann-La Roche AG

  公开号：EP2613775B1

  公开（公告）日：2014-07-30
• US8716285B2
  申请人：——

  公开号：US8716285B2

  公开（公告）日：2014-05-06