(E)-6-(naphthalen-2-yl)imidazo[2,1-b]oxazole-5-carbaldehyde O-(4-methoxybenzyl) oxime

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (E)-6-(naphthalen-2-yl)imidazo[2,1-b]oxazole-5-carbaldehyde O-(4-methoxybenzyl) oxime
• 英文别名: (E)-N-[(4-methoxyphenyl)methoxy]-1-(6-naphthalen-2-ylimidazo[2,1-b][1,3]oxazol-5-yl)methanimine
• 化学式: C₂₄H₁₉N₃O₃
• 分子量: 397.433
• InChiKey: MEPUCKXPTANYOU-MFKUBSTISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  61.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-溴代-2-乙酰基萘 在 四氯化钛 、 溶剂黄146 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 、 甲苯 、 乙腈 为溶剂， 反应 33.5h， 生成 (E)-6-(naphthalen-2-yl)imidazo[2,1-b]oxazole-5-carbaldehyde O-(4-methoxybenzyl) oxime
  参考文献：
  名称：

  DL5050, a Selective Agonist for the Human Constitutive Androstane Receptor

  摘要：

  The constitutive androstane receptor (CAR) is a xenobiotic sensor governing the transcription of genes involved in drug disposition, energy homeostasis, and cell proliferation. However, currently available human CAR (hCAR) agonists are nonselective, which commonly activate hCAR along with other nuclear receptors, especially the closely related human pregnane X receptor (hPXR). Using a well-known hCAR agonist CITCO as a template, we report our efforts in the discovery of a potent and highly selective hCAR agonist. Two of the new compounds of the series, 18 and 19 (DL5050), demonstrated excellent potency and selectivity for hCAR over hPXR. DL5050 preferentially induced the expression of CYP2B6 (target of hCAR) over CYP3A4 (target of hPXR) on both the mRNA and protein levels. The selective hCAR agonist DL5050 represents a valuable tool molecule to further define the biological functions of hCAR, and may also be used as a new lead in the discovery of hCAR agonists for various therapeutic applications.

  DOI：

  10.1021/acsmedchemlett.9b00079

文献信息

• CAR ACTIVATOR AGENTS FOR CYCLOPHOSPHAMIDE-BASED TREATMENTS OF CANCER
  申请人：UNIVERSITY OF MARYLAND, BALTIMORE

  公开号：US20200352915A1

  公开（公告）日：2020-11-12

  The invention relates to selective small molecule human constitutive androstane receptor (hCAR) activators of Formula (I) or (II), pharmaceutical compositions thereof, and use thereof for the treatment of hematologic malignancies and other cancers. The small molecule hCAR activator in combination with CPA based chemotherapy regimen provides a synergistic effect to help promote cytoxicity of the cyclophosphamide (CPA) based anticancer treatments including CHOP regimen (CPA, doxorubicin, vincristine, and prednisone) by preferential induction of CYP2B6 over CYP3A4 and promoting the formation of therapeutically active CPA metabolite 4-OH-CPA.