ICARIIN衍生物 | 1067198-74-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 中文名称: ICARIIN衍生物
• 中文别名: Icariin衍生物
• 英文名称: 3,7-bis(2-hydroxyethyl)icaritin
• 英文别名: 5-hydroxy-3,7-bis(2-hydroxyethoxy)-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)-4H-chromen-4-one；5-hydroxy-3,7-bis(2-hydroxyethoxy)-2-(4-methoxyphenyl)-8-(3-methylbut-2-enyl)chromen-4-one
• CAS: 1067198-74-6
• 化学式: C₂₅H₂₈O₈
• 分子量: 456.493
• InChiKey: WTJGVHRGWYENBZ-UHFFFAOYSA-N

物化性质

• 沸点：
  710.3±60.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  115
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ICARIIN衍生物 在 吡啶 、 三氧化硫 、 碳酸氢钠 作用下， 以20%的产率得到disodium ((5-hydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)-4-oxo-4H-chromene-3,7-diyl)bis(oxy))bis(ethane-1,2-diyloxy) disulfonate
  参考文献：
  名称：

  淫羊藿苷类化合物及其应用

  摘要：

  本发明涉及淫羊藿苷类化合物、及其在制备预防和治疗骨折和骨质疏松的药物中的应用。特别的，本发明涉及通式(I)所示的化合物，其中或其立体异构体、几何异构体、互变异构体、氮氧化物、水合物、溶剂化物、代谢产物、药学上可接受的盐或前药，各变量如说明书所定义。本发明还涉及通式(I)所示的化合物其立体异构体、几何异构体、互变异构体、氮氧化物、水合物、溶剂化物、代谢产物、药学上可接受的盐或前药的盐作为药物的用途，尤其是作为用于预防和治疗骨折和骨质疏松的药物的用途。

  公开号：

  CN104529974B
• 作为产物：
  描述：

  宝藿苷I 在 硫酸 、 potassium carbonate 作用下， 以 乙醇 、 水 、 丙酮 为溶剂， 反应 5.0h， 生成 ICARIIN衍生物
  参考文献：
  名称：

  淫羊藿苷类化合物及其应用

  摘要：

  本发明涉及淫羊藿苷类化合物、及其在制备预防和治疗骨折和骨质疏松的药物中的应用。特别的，本发明涉及通式(I)所示的化合物，其中或其立体异构体、几何异构体、互变异构体、氮氧化物、水合物、溶剂化物、代谢产物、药学上可接受的盐或前药，各变量如说明书所定义。本发明还涉及通式(I)所示的化合物其立体异构体、几何异构体、互变异构体、氮氧化物、水合物、溶剂化物、代谢产物、药学上可接受的盐或前药的盐作为药物的用途，尤其是作为用于预防和治疗骨折和骨质疏松的药物的用途。

  公开号：

  CN104529974B

文献信息

• 一种淫羊藿苷元衍生物及其制备方法和用途
  申请人：鲁南制药集团股份有限公司

  公开号：CN110357844A

  公开（公告）日：2019-10-22

  本发明属于药物化学领域，具体涉及淫羊藿苷元衍生物，如式(I)，及其药理学上容许的盐以及其制备方法，以及其在制备治疗哮喘，骨髓抑制方面药物的用途。
• 淫羊藿素衍生物及其制备方法和用途
  申请人：中国科学院华南植物园

  公开号：CN104610212B

  公开（公告）日：2017-04-26

  本发明公开了淫羊藿素衍生物及其制备方法和用途。淫羊藿素衍生物，其结构如式(1)表示，其中，化合物1：m＝2，n＝3；或化合物2：m＝3，n＝3。本发明的淫羊藿素衍生物水溶性更好，抗肿瘤活性更强，对正常细胞毒性更低，能用于制备抗肿瘤药物，具有广泛的应用前景。
• Synthesis and cancer cell growth inhibitory activity of icaritin derivatives
  作者：Chen Wang、Ping Wu、Jing-Fang Shi、Zi-Hua Jiang、Xiao-Yi Wei

  DOI：10.1016/j.ejmech.2015.06.006

  日期：2015.7

  A series of icaritin derivatives bearing carboxylic acid or carboxylic ester groups are synthesized, and their in vitro cytotoxic activity against three cancer cell lines, MCF-7, MDA-MB-435s, and A549, are evaluated by MTT assay. Several derivatives including 2h, 2j, 5b and 5d show higher cytotoxic activity than the parent compound icaritin against these cancer cell lines. Compounds 5b and 5d are even more cytotoxic to MCF-7 cells than the clinic drug tamoxifen. Moreover, compound 5b is found to be non-toxic to normal cells (Vero) and both 5b and 5d exhibit good selectivity towards estrogen receptor positive MCF-7 breast cancer cells over estrogen receptor negative MDA-MB-435s breast cancer cells. The structure activity relationship analysis has revealed that mono-substitution at either C-3 or C-7 hydroxyl group of icaritin could improve the cytotoxicity of icaritin, and the C-3 hydroxyl group may be a preferable site for chemical modification. In addition, the length, the flexibility and the additional branching substituent group of the substitution chain(s) at both C-3 and C-7 hydroxyl groups can all affect the anticancer activity of these derivatives. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Potent Inhibition of Human Phosphodiesterase-5 by Icariin Derivatives
  作者：Mario Dell’Agli、Germana V. Galli、Esther Dal Cero、Federica Belluti、Riccardo Matera、Elisa Zironi、Giampiero Pagliuca、Enrica Bosisio

  DOI：10.1021/np800049y

  日期：2008.9.1

  Plant extracts traditionally used for male impotence (Tribulus terrestris, Ferula hermonis, Epimedium brevicornum, Cinnamomum cassia), and the individual Compounds cinnamaldehyde, ferutinin, and icariin, were screened against phosphodiesterase-5A1 (PDE5A1) activity. Human recombinant PDE5A1 was used as the enzyme source. Only E. brevicornum extract (80% inhibition at 50 mu g/mL) and its active principle icariin (1) (IC50 5.9 mu M) were active. To improve its inhibitory activity, 1 was subjected to various structural modifications. Thus, 3,7-bis(2-hydroxyethyl)icaritin (5), where both sugars in 1 were replaced with hydroxyethyl residues, potently inhibited PDE5A1 with an IC50 very close to that of sildenafil (IC50 75 vs 74 nM). Thus, 5 was 80 times more potent than 1, and its selectivity versus phosphodiesterase-6 (PDE6) and cyclic adenosine in monophosphate-phosphodiesterase (cAMP-PDE) was much higher in comparison with sildenafil. The improved pharmacodynamic profile and lack of cytotoxicity on human fibroblasts make compound 5 a promising candidate for further development.
• 3,7-Bis(2-hydroxyethyl)icaritin, a potent inhibitor of phosphodiesterase-5, prevents monocrotaline-induced pulmonary arterial hypertension via NO/cGMP activation in rats
  作者：Tao-Hua Lan、Xiao-Ling Chen、Yun-Shan Wu、Hui-Liang Qiu、Jun-Zhe Li、Xin-Min Ruan、Dan-Ping Xu、Dong-Qun Lin

  DOI：10.1016/j.ejphar.2018.04.011

  日期：2018.6

  Pulmonary arterial hypertension (PAH) is a chronic progressive disease which leads to elevated pulmonary arterial pressure and right heart failure. 3,7-Bis(2-hydroxyethyl)icaritin (ICT), an icariin derivatives, was reported to have potent inhibitory activity on phosphodiesterase type 5 (PDE5) which plays a crucial role in the pathogenesis of PAH. The present study was designed to investigate the effects of ICT on monocrotaline (MCT)induced PAH rat model and reveal the underlying mechanism. MCT-induced PAH rat models were established with intragastric administration of ICT (10, 20, 40 mg/kg/d), Icariin (ICA) (40 mg/kg/d) and Sildenafil (25 mg/ kg/d). The mean pulmonary arterial pressure (mPAP) and right ventricle hypertrophy index (RVHI) were measured. Pulmonary artery remodeling was assessed by H&E staining. Blood and lung tissue were collected to evaluate the level of endothelin 1 (ET-1), nitric oxide (NO), and cyclic guanosine monophosphate (cGMP). The expressions endothelial nitric oxide synthase (eNOS) and PDE5A in lung tissues were determined by Western blot analysis. The results showed that ICT reduced RVHI and mPAP, and reversed lung vascular remodeling in rats with MCT-induced PAH. ICT also reversed MCT-induced ET-1 elevation, NO and cGMP reduction in serum or lung tissue. Moreover, ICT administration significantly induced eNOS activation and PDE5A inhibition. ICT with lower dose had better effects than ICA. In summary, ICT is more effective in preventing MCT-induced PAH in rats via NO/cGMP activation compared with ICA. These findings demonstrate a novel mechanism of the action of ICT that may have value in prevention of PAH.