(3E,5E)-1-methyl-3,5-bis((5-methyl-1,2-oxazol-3-yl)methylene)piperidin-4-one | 1578301-12-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (3E,5E)-1-methyl-3,5-bis((5-methyl-1,2-oxazol-3-yl)methylene)piperidin-4-one
• 英文别名: (3E,5E)-1-methyl-3,5-bis[(5-methyl-1,2-oxazol-3-yl)methylidene]piperidin-4-one
• CAS: 1578301-12-8
• 化学式: C₁₆H₁₇N₃O₃
• 分子量: 299.329
• InChiKey: PQWMKPLFEFLPTN-PWHKKFIBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  72.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-甲基-4-哌啶酮 、 5-甲基异恶唑-3-甲醛 在 sodium methylate 作用下， 以 甲醇 为溶剂， 以49%的产率得到(3E,5E)-1-methyl-3,5-bis((5-methyl-1,2-oxazol-3-yl)methylene)piperidin-4-one
  参考文献：
  名称：

  THERAPEUTIC USES OF CURCUMIN ANALOGS FOR TREATMENT OF PROSTATE CANCER

  摘要：

  本发明涉及一般用于治疗侵袭性癌症的方法，例如激素难治性转移性前列腺癌，通过将侵袭性癌细胞暴露于具有所述结构支架和侧基团的姜黄素类似物中。姜黄素的抗癌作用与其对细胞内众多生长因子的影响有关。然而，由于在水中溶解度差和体内代谢迅速导致的生物利用度差，其临床开发受到了限制。需要开发新的和改进的姜黄素类似物，具有更好的效力、水溶性和体内代谢稳定性，以及保持安全性。具有所述四种新型支架之一和含有碱性杂环侧基团的姜黄素类似物表现出降低侵袭性癌细胞生存能力和抑制侵袭性癌细胞生长的能力。

  公开号：

  US20150017720A1

文献信息

• THERAPEUTIC USES OF CURCUMIN ANALOGS FOR TREATMENT OF PROSTATE CANCER
  申请人：California State University Fresno

  公开号：US20150017720A1

  公开（公告）日：2015-01-15

  This invention relates generally to methods of treating aggressive cancers, such as hormone-refractory metastatic prostate cancer, by exposing the aggressive cancer cells to curcumin analogs having the claimed structural scaffolds and side groups. The anticancer effects of curcumin are associated with its influence on numerous growth factors within the cells. However, its clinical development has been limited by its suboptimal pharmacokinetics and poor bioavailability caused by poor solubility in water and rapid in vivo metabolism. There is the need to develop new and improved curcumin analogs with better potency, water solubility, and in vivo metabolic stability, as well as retained safety profiles. Curcumin analogs having one of the claimed four novel scaffolds with basic heteroaromatic side groups show the ability to decrease aggressive cancer cell viability and to inhibit aggressive cancer cell growth.

  本发明涉及一般用于治疗侵袭性癌症的方法，例如激素难治性转移性前列腺癌，通过将侵袭性癌细胞暴露于具有所述结构支架和侧基团的姜黄素类似物中。姜黄素的抗癌作用与其对细胞内众多生长因子的影响有关。然而，由于在水中溶解度差和体内代谢迅速导致的生物利用度差，其临床开发受到了限制。需要开发新的和改进的姜黄素类似物，具有更好的效力、水溶性和体内代谢稳定性，以及保持安全性。具有所述四种新型支架之一和含有碱性杂环侧基团的姜黄素类似物表现出降低侵袭性癌细胞生存能力和抑制侵袭性癌细胞生长的能力。
• Design, synthesis, and evaluation of novel heteroaromatic analogs of curcumin as anti-cancer agents
  作者：Nawras Samaan、Qiu Zhong、Jayjoel Fernandez、Guanglin Chen、Ali M. Hussain、Shilong Zheng、Guangdi Wang、Qiao-Hong Chen

  DOI：10.1016/j.ejmech.2014.01.041

  日期：2014.3

  To improve the potential of curcumin to treat advanced hormone-refractory prostate cancer, three series (A-C) of heteroaromatic analogs (thirty two compounds) with different monoketone linkers have been synthesized and evaluated for cytotoxicity against two human androgen-independent prostate cancer cell lines (PC-3 and DU-145). Among them, thirty analogs are more potent than curcumin against PC-3 cells, and twenty one analogs are more cytotoxic towards DU-145 cells relative to curcumin. The most potent compounds (44, 45, 51, and 52) also showed impressive cytotoxicity against three other metastatic cancer cell lines (MDA-MB-231, HeLa, and A549), with IC50 values ranging from 50 nM to 390 nM. All four most potent analogs exhibited no apparent cytotoxicity towards the MCF-10A normal mammary epithelial cells. Taken together, selective enhancement of cell death in prostate cancer cell lines and other aggressive cancer cell lines suggests that nitrogen-containing heteroaromatic rings are promising bio-isosteres of the substituted phenyl ring in curcumin. Published by Elsevier Masson SAS.