3-[1-(naphthyl-2-yl)methyl-2-oxo-1,2,5,6-tetrahydro-pyridin-3-yl]-propionic acid methyl ester | 798544-02-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-[1-(naphthyl-2-yl)methyl-2-oxo-1,2,5,6-tetrahydro-pyridin-3-yl]-propionic acid methyl ester
• CAS: 798544-02-2
• 化学式: C₂₀H₂₁NO₃
• 分子量: 323.392
• InChiKey: ZBDLRFVCXVRWJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.45
• 重原子数：
  24.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  46.61
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3-[1-(naphthyl-2-yl)methyl-2-oxo-1,2,5,6-tetrahydro-pyridin-3-yl]-propionic acid methyl ester 在 羟胺钾盐 作用下， 以 甲醇 为溶剂， 生成 N-hydroxy-3-(1-(naphthalene-2-yl-methyl)-2-oxo-1,2,5,6-tetrahydro-pyridin-3-yl)-propionamide
  参考文献：
  名称：

  基于内酰胺的HDAC抑制剂用于抗癌化学疗法：通过翻译后修饰和表观遗传控制恢复RUNX3

  摘要：

  肿瘤抑制子相关转录因子3（RUNX3）的表达和稳定性受组蛋白脱乙酰基酶（HDAC）调节。HDAC抑制会改变RUNX3的表观遗传和翻译后稳定性，从而导致肿瘤抑制。但是，HDAC抑制剂可以通过染色质重塑非选择性地改变全局基因的表达。因此，筛选了基于内酰胺的HDAC抑制剂以鉴定有效的蛋白质稳定剂，该稳定剂可通过乙酰化保持RUNX3的稳定性。通过基于细胞的RUNX激活和HDAC抑制测定法确定了111种基于内酰胺的类似物的RUNX活性和HDAC抑制作用。3- [1-（4-溴苄基）-2-氧代-2,5-二氢-1 H-吡咯-3-基] -N-羟基丙酰胺（11-8）可显着提高RUNX3的乙酰化和稳定性，并具有相对较低的RUNX3 mRNA表达和HDAC抑制活性。在MKN28异种移植模型中，该化合物显示出显着的抗肿瘤作用，比SAHA强。因此，我们提出了一种新的策略，其中HDAC抑制剂用作选择性靶向RUNX3的表

  DOI：

  10.1002/cmdc.201300393
• 作为产物：
  描述：

  N-(naphthalen-2-ylmethyl)but-3-en-1-amine 在 Grubbs catalyst first generation 4-二甲氨基吡啶 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 生成 3-[1-(naphthyl-2-yl)methyl-2-oxo-1,2,5,6-tetrahydro-pyridin-3-yl]-propionic acid methyl ester
  参考文献：
  名称：

  Modification of cap group in δ-lactam-based histone deacetylase (HDAC) inhibitors

  摘要：

  Novel delta-lactam-based HDAC inhibitors which have various substituted benzyl, bi-aromatic cap groups were prepared using ring closure metathesis reaction, and evaluated their HDAC inhibitory activities and anti-proliferative effects. Among prepared analogues, 11m and 11o have very strong HDAC enzymatic inhibition and showed the most potent growth inhibitory activity to five human tumor cell lines including PC-3, ACHN, NUGC-3, HCT-15, and MBA-MB-231 tumor cell lines. Compounds 11m and 11o also showed good tumor growth inhibition of MDA-MB-231 cells in in vivo xenograft model. Structure-activity relationship study using docking model explained the significance of hydrophobic aromatic cap groups for their in vitro activities. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.09.034

文献信息

• [EN] NOVEL 2-OXO-HETEROCYCLIC COMPOUNDS AND THE PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME<br/>[FR] NOUVEAUX COMPOSES 2-OXO-HETEROCYCLIQUES ET COMPOSITIONS PHARMACEUTIQUES CONTENANT CES COMPOSES
  申请人：KOREA RES INST OF BIOSCIENCE

  公开号：WO2004101523A1

  公开（公告）日：2004-11-25

  The present invention is related to new 2-oxo-cyclic compound the process for preparing them and a pharmaceutical composition comprising the same. The present invention provides a pharmaceutical composition for preventing and treating the inflammatory disease comprising the pain or inflammation caused by rheumatic disease, for example, rheumatoid arthritis, spondyloarthopathies, gout, osteoarthritis, systemic lupus erythematosus and juvenile arthritis, and inflammatory syndrome for example, from myositis, gingivitis, synovitis, ankylosing spondylitis, burstitis, burns and scar, inflammatory Crohn's disease, Types I diabetes. therefore, it can be used as the therapeutics for treating and preventing inflammatory diseases.

  本发明涉及新的2-氧代环化合物及其制备方法和包含其的药物组合物。本发明提供了一种用于预防和治疗炎症性疾病的药物组合物，包括由风湿性疾病引起的疼痛或炎症，例如类风湿性关节炎、脊柱关节病、痛风、骨关节炎、全身性红斑狼疮和儿童关节炎，以及炎症综合征，例如肌炎、牙龈炎、滑囊炎、强直性脊柱炎、滑囊炎、烧伤和疤痕、炎症性克罗恩病、I型糖尿病等。因此，它可以用作治疗和预防炎症性疾病的治疗药物。