3-(3,5-di-((E)-dec-1-enyl)-4,6-dimethylpyridin-2-yl)propan-1-ol

• 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
• 英文名称: 3-(3,5-di-((E)-dec-1-enyl)-4,6-dimethylpyridin-2-yl)propan-1-ol
• 英文别名: 3-[3,5-bis[(E)-dec-1-enyl]-4,6-dimethylpyridin-2-yl]propan-1-ol
• 化学式: C₃₀H₅₁NO
• 分子量: 441.741
• InChiKey: BBIHADVXXJRNBU-WDAKLKSISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11
• 重原子数：
  32
• 可旋转键数：
  19
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(3,5-di-((E)-dec-1-enyl)-4,6-dimethylpyridin-2-yl)propan-1-ol 在 10% Pd/C 作用下， 以71%的产率得到6,8-bis[(E)-dec-1-enyl]-5,7-dimethyl-2,3-dihydro-1H-indolizin-4-ium;chloride
  参考文献：
  名称：

  天然产物趋化因子受体CCR5拮抗剂阿尼巴明对新型抗前列腺癌药物发展的结构活性关系研究

  摘要：

  最近的研究表明，CCR5趋化因子受体可能是治疗前列腺癌的潜在靶标。因此，CCR5拮抗剂的开发可以提供新颖的前列腺癌治疗方法。发现Anibamine是一种从Aniba sp。分离的新型吡啶季生物碱，其与趋化因子受体CCR5的结合可有效与125 I-gp120竞争，其IC 50为50 = 1μM。茴香胺是第一个被报道为CCR5拮抗剂的天然产物，因此提供了一种不同于其他先导化合物的新颖结构骨架，而这些先导化合物通常是从高通量筛选工作中鉴定出来的。为了改善先导化合物的结构并提高阿尼巴胺衍生物作为潜在的抗前列腺癌药物的治疗指数，在这项工作的结构-活性关系研究中采用了“解构-重建-精制”的方法。在这里，我们报告阿尼巴明和17类似物的设计，合成和抗前列腺癌活性。从结果在体外和体内在此描述的研究表明，这类化合物有潜力提供新颖的引线作为抗前列腺癌试剂。

  DOI：

  10.1016/j.ejmech.2012.07.049
• 作为产物：
  描述：

  trans-1-dec-1-enyl boronic acid 在 盐酸 、 palladium diacetate 、 sodium carbonate 、 三苯基膦 作用下， 以 乙醇 为溶剂， 生成 3-(3,5-di-((E)-dec-1-enyl)-4,6-dimethylpyridin-2-yl)propan-1-ol
  参考文献：
  名称：

  天然产物趋化因子受体CCR5拮抗剂阿尼巴明对新型抗前列腺癌药物发展的结构活性关系研究

  摘要：

  最近的研究表明，CCR5趋化因子受体可能是治疗前列腺癌的潜在靶标。因此，CCR5拮抗剂的开发可以提供新颖的前列腺癌治疗方法。发现Anibamine是一种从Aniba sp。分离的新型吡啶季生物碱，其与趋化因子受体CCR5的结合可有效与125 I-gp120竞争，其IC 50为50 = 1μM。茴香胺是第一个被报道为CCR5拮抗剂的天然产物，因此提供了一种不同于其他先导化合物的新颖结构骨架，而这些先导化合物通常是从高通量筛选工作中鉴定出来的。为了改善先导化合物的结构并提高阿尼巴胺衍生物作为潜在的抗前列腺癌药物的治疗指数，在这项工作的结构-活性关系研究中采用了“解构-重建-精制”的方法。在这里，我们报告阿尼巴明和17类似物的设计，合成和抗前列腺癌活性。从结果在体外和体内在此描述的研究表明，这类化合物有潜力提供新颖的引线作为抗前列腺癌试剂。

  DOI：

  10.1016/j.ejmech.2012.07.049

文献信息

• Total Synthesis of Anibamine, a Novel Natural Product as a Chemokine Receptor CCR5 Antagonist
  作者：Guo Li、Karen Watson、Robert W. Buckheit、Yan Zhang

  DOI：10.1021/ol070748n

  日期：2007.5.1

  The total synthesis of anibamine, the first and only natural product known as a chemokine receptor CCR5 antagonist, is reported herein. Anibamine was synthesized from acetylacetone and cyanoacetamide in 10 steps.
• The natural product CCR5 antagonist anibamine and its analogs as anti-prostate cancer agents
  作者：Kendra M. Haney、Feng Zhang、Christopher K. Arnatt、Yunyun Yuan、Guo Li、Joy L. Ware、David A. Gewirtz、Yan Zhang

  DOI：10.1016/j.bmcl.2011.07.058

  日期：2011.9

  Prostate cancer is a leading cause of death among males in the United States. As the chemokine receptor CCR5 is over-expressed in more aggressive forms of prostate cancer, and is also a critical receptor in inflammation, chemokine receptor CCR5 antagonists could potentially act as anti-prostate cancer agents. Anibamine, a natural product CCR5 antagonist, provides a unique molecular scaffold for the generation of novel analogs with possible anti-prostate cancer activity. A series of analogs of anibamine were designed, synthesized and tested against several prostate cancer cell lines. The analogs all acted as CCR5 antagonists at micromolar range affinity to the receptor while their anti-proliferative activity varied depending on the cell line type and their chemical structural properties. Further basal cytotoxicity characterization on these compounds indicated some of them may be suitable for in vivo studies. Published by Elsevier Ltd.
• The potential role of anibamine, a natural product CCR5 antagonist, and its analogues as leads toward development of anti-ovarian cancer agents
  作者：Yan Zhang、Christopher K. Arnatt、Feng Zhang、Jiannan Wang、Kendra M. Haney、Xianjun Fang

  DOI：10.1016/j.bmcl.2012.05.127

  日期：2012.8

  Chemokines and their receptors play important roles in the development of primary tumors and their metastases. Particularly CC chemokine receptor 5 (CCR5) and its ligand CC chemokine ligand 5 (CCL5/RANTES) seem to be critical in proliferation and invasion of ovarian cancer, the leading cause of death from gynecological malignancies in the United States. Anibamine, the first natural product CCR5 antagonist, and its analogues were examined for their effects on proliferation of the OVCAR-3 ovarian cancer cells in order to validate their candidacy as leads to develop novel anti-ovarian cancer agents. Acting as CCR5 antagonists, anibamine and its analogues significantly suppressed CCL5-induced intracellular Ca2+ flux. The compounds also inhibited the proliferation of OVCAR-3 at micromolar to submicromolar range. Moreover, anibamine and several analogues did not show significant cytotoxicity in NIH 3T3 cells at concentrations up to 20 mu M. Based on these results, anibamine and one of its synthetic analogues were defined as potential leads to develop novel agents against ovarian cancer. Published by Elsevier Ltd.