7-[2-(环丙基甲氧基)-6-羟基苯基]-1,4-二氢-5-[(3S)-3-哌啶基]-2H-吡啶并[2,3-d][1,3]恶嗪盐酸盐 | 600734-06-3

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 7-[2-(环丙基甲氧基)-6-羟基苯基]-1,4-二氢-5-[(3S)-3-哌啶基]-2H-吡啶并[2,3-d][1,3]恶嗪盐酸盐
• 英文名称: (-)-7-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-5-[(3S)-3-piperidinyl]-1,4-dihydro-2H-pyrido[2,3-d][1,3]oxazin-2-one hydrochloride
• 英文别名: 7-[2-(Cyclopropylmethoxy)-6-hydroxyphenyl]-1,4-dihydro-5-[(3S)-3-piperidinyl]-2H-pyrido[2,3-d][1,3]oxazin-2-one hydrochloride；7-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-5-[(3S)-piperidin-3-yl]-1,4-dihydropyrido[2,3-d][1,3]oxazin-2-one;hydrochloride
• CAS: 600734-06-3
• 化学式: C₂₂H₂₅N₃O₄*ClH
• 分子量: 431.919
• InChiKey: XZTOAEZYOFWVHB-PFEQFJNWSA-N

物化性质

• 溶解度：
  DMSO：50 mg/mL（115.76 mM；需要超声）

计算性质

• 辛醇/水分配系数(LogP)：
  4.19
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  92.7
• 氢给体数：
  4
• 氢受体数：
  6

制备方法与用途

生物活性

Bay 65-1942 hydrochloride 是一种 ATP 竞争性的选择性 IKKβ 抑制剂。

靶点

IKKβ

体外研究

Delivery of Bay 65-1942 prior to ischemia significantly decreases left ventricular infarct size compared with animals receiving vehicle. Compared with sham animals, animals receiving vehicle have a significant increase in the infarct-to-area at risk (AAR) ratio (70.7±3.4 vs. 5.8±3.4%, P<0.05). This ratio is significantly reduced by treatment with Bay 65-1942 at each time point (prior to ischemia 42.7±4.1%, at reperfusion 42.7±7.5%, 2 h of reperfusion 29.4±5.2%; each group P<0.05 vs. vehicle). Animals pretreated with Bay 65-1942 (n=3) have significantly attenuated CK-MB levels compared with those animals without treatment prior to IR (14,170 ±3,219 units, P<0.05 vs. vehicle).

体内研究

Inhibitors of MEK (AZD6244) and IKK (BAY 65-1942) are used at their IC ₅₀ concentrations, as determined by a 48 hour MTS assay, which achieve sufficient inhibition of kinase activity. MYL-R cells are treated for 24 hours with AZD6244 (5 µM), BAY 65-1942 (10 µM), or a combination of these inhibitors at the same concentrations. AZD6244 and BAY 65-1942 demonstrate synergistic inhibition of cell viability at the dose combination (5 µM AZD6244+10 µM BAY 65-1942), which correlates with IC ₇₅ (CI = 0.48±0.01). Synergism is also indicated at the IC ₅₀ (CI = 0.56±0.09) and IC ₉₀ (CI = 0.46±0.02) dose combinations reported by the software (CI values are the mean of three independent experiments, ± standard deviation). AZD6244 and BAY 65-1942 treatment induces 2- and 1.3-fold caspase 3/7 activation, respectively, compared to the DMSO-treated cells. Treatment with a combination of AZD6244 plus BAY 65-1942 leads to a 3.2-fold increase in caspase 3/7 activity.

反应信息

• 作为产物：
  描述：

  tert-butyl (3S)-(-)-3-(7-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-2-oxo-1,4-dihydro-2H-pyrido[2,3-d][1,3]oxazin-5-yl)-1-piperidinecarboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以71%的产率得到7-[2-(环丙基甲氧基)-6-羟基苯基]-1,4-二氢-5-[(3S)-3-哌啶基]-2H-吡啶并[2,3-d][1,3]恶嗪盐酸盐
  参考文献：
  名称：

  [EN] AN OPTICALLY ACITVE PYRIDINE DERIVATIVE AND A MEDICAMENT CONTAINING THE SAME
  [FR] DERIVE DE PYRIDINE OPTIQUEMENT ACTIF ET MEDICAMENT CONTENANT CE DERNIER

  摘要：

  一种具有优异抗炎活性和其他生物活性的光学活性化合物(-)-7-[2-(环丙基甲氧基)-6-羟基苯基]-5-[(3S)-3-哌啶基]-1,4-二氢-2H-吡啶[2,3-d][1,3]噁唑啉-2-酮（I）的盐或其盐。

  公开号：

  WO2003076447A1

文献信息

• Optically active pyridine derivative and a medicament containing the same
  申请人：Murata Toshiki

  公开号：US20050215547A1

  公开（公告）日：2005-09-29

  An optically active (−)-7-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-5-[(3S)-3-piperidinyl]-1,4-dihydro-2H-pyrido[2,3-d][1,3]α-azin-2-one of the formula (I) or salt thereof. The compound has an excellent anti-inflammatory activity, and other biological activity.

  一种旋光性的(-)-7-[2-(环丙基甲氧基)-6-羟基苯基]-5-[(3S)-3-哌啶基]-1,4-二氢-2H-吡啶[2,3-d][1,3]α-氮杂-2-酮(I式)或其盐。该化合物具有出色的抗炎活性和其他生物活性。
• AN OPTICALLY ACITVE PYRIDINE DERIVATIVE AND A MEDICAMENT CONTAINING THE SAME
  申请人：Bayer HealthCare AG

  公开号：EP1487842B1

  公开（公告）日：2007-03-14
• INHIBITING THE SIGNS OF AGING BY INHIBITING NF-KAPPA B ACTIVATION
  申请人：Robbins Paul D.

  公开号：US20090075902A1

  公开（公告）日：2009-03-19

  The present invention relates to methods and compositions for reducing and/or delaying one or more signs of aging which comprise inhibiting NF-kappa B activation. It is based, at least in part, on the discovery that a peptide which inhibits IKK-β interaction with NEMO, linked to a transducing peptide, inhibits the development of various indicia of senescence in a murine model of aging, Ercc1 −/Δ mice.
• NEURAL STEM CELL THERAPY FOR OBESITY AND DIABETES
  申请人：ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIVERSITY

  公开号：US20140363407A1

  公开（公告）日：2014-12-11

  Methods are provided of treating obesity or an obesity comorbidity in a mammalian subject comprising administering to the subject an amount of an agent effective to treat obesity or the obesity comorbidity, which agent inhibits (i) IκB kinase β (IKKβ) activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) or (ii) Notch signaling in a manner so as to permit the agent to enter the hypothalamus of the subject. Assays are also provided for identifying candidate agents for treating obesity.
• US7375103B2
  申请人：——

  公开号：US7375103B2

  公开（公告）日：2008-05-20