(1E,4Z,6E)-1-(3,4-dimethoxyphenyl)-5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: (1E,4Z,6E)-1-(3,4-dimethoxyphenyl)-5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one
• 英文别名: monomethylcurcumin
• 化学式: C₂₂H₂₂O₆
• 分子量: 382.413
• InChiKey: MXGYVBOZRLQICP-VUSYVUDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.16
• 重原子数：
  28.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  85.22
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  布洛芬 、 (1E,4Z,6E)-1-(3,4-dimethoxyphenyl)-5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 氯仿 为溶剂， 以155 mg的产率得到4-((1E,3Z,6E)-3-hydroxy-(4-hydroxy-3-methoxyphenyl)-5-oxohepta-1,3,3-trienyl)-2-methoxyphenyl-2-(4-isobutylphenyl)propanoate
  参考文献：
  名称：

  姜黄素-NSAIDs 前药的一锅合成、光谱表征、构象分析、化学反应性、分子内相互作用和 DFT 方法的一级超极化

  摘要：

  摘要 一种新型姜黄素-NSAIDs 前药 4-((1E, 3Z, 6E)-3-羟基-(4-羟基-3-甲氧基苯基)-5-氧代庚烷-1,3,3-三烯基)-2-甲氧基苯基-2 -（4-异丁基苯基）丙酸酯（2）衍生物通过 Steglich 酯化反应以高产率合成，并借助 1 H、 13 C NMR、 1 H– 1 H COSY、UV、FT-IR 光谱和质谱进行表征。通过密度泛函理论 (DFT/B3LYP) 使用两种不同的基组 6-31G (d, p) 和 6-311G (d, p) 在基态下计算合成化合物的分子几何形状。进行2的构象分析以确定最稳定的构象。使用自然键轨道 (NBO) 分析法分析作为超共轭相互作用和电子离域结果的分子稳定性。通过AIM（分子中的原子）方法分析分子内相互作用。计算全局和局部反应性描述符以研究分子内的反应位点。使用时间相关密度泛函理论 (TD-DFT) 计算电子特性，例如 HOMO

  DOI：

  10.1016/j.molstruc.2016.03.033
• 作为产物：
  描述：

  curcumin 、 碘甲烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 以51.5%的产率得到(1E,4Z,6E)-1-(3,4-dimethoxyphenyl)-5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one
  参考文献：
  名称：

  Anti-allergic principles from Thai zedoary: structural requirements of curcuminoids for inhibition of degranulation and effect on the release of TNF-α and IL-4 in RBL-2H3 cells

  摘要：

  The 80% aqueous acetone extract of the rhizomes of Curcuma zedoaria cultivated in Thailand (Thai zedoary) was found to inhibit release of beta-hexosaminidase, as a marker of antigen-IgE-mediated degranulation, in RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice. From the active fraction, four curcuminoids (curcumin, dihydrocurcumin, tetra-hydrodemethoxycurcumin, and tetrahydrobisdemethoxycurcumin) were isolated together with two bisabolane-type sesquiterpenes, and the effects of four curcuminoids from Thai zedoary and several related compounds on the degranulation were examined. Among them, curcumin showed the highest activity against beta-hexosaminidase release with IC50 of 5.3 hM, followed by bisdemethoxycurcumin (IC50 = 11muM). With regard to the structural requirements of curcuminoids for the activity, the conjugated olefins at the 1-7 positions and the 4'- or 4"-hydroxyl groups of curcuminoids were suggested to be essential for the strong activity, whereas the 3'- or 3"-methoxyl group only enhanced the activity. Furthermore, effects of curcumin and bisdemethoxycurcumin on calcium ionophores (A23187 and ionomycin)-induced degranulation and antigen-induced release of TNF-alpha and IL-4 were examined. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.08.027

文献信息

• Pharmaceutical Combinations Including Anti-Inflammatory and Antioxidant Conjugates Useful for Treating Metabolic Disorders
  申请人：Laria Julio Cesar Castro Palomino

  公开号：US20150025006A1

  公开（公告）日：2015-01-22

  One aspect of the present invention is a pharmaceutical combination comprising (a) an anti-inflammatory agent/anti-oxidant agent conjugate; and (b) an insulin secretogogue, an insulin sensitizer, an alpha-glucosidase inhibitor, a peptide analog, or a combination thereof. Another aspect of the invention relates to methods of treating metabolic disorders with such conjugates.

  本发明的一个方面是一种药物组合，包括（a）一种抗炎/抗氧化药物偶联物；以及（b）一种胰岛素分泌素、胰岛素敏感剂、α-葡萄糖苷酶抑制剂、肽类类似物或其组合。本发明的另一个方面涉及使用这种偶联物治疗代谢性疾病的方法。
• Anti-Inflammatory And Antioxidant Conjugates Useful For Treating Metabolic Disorders
  申请人：Genmedica Therapeutics SL

  公开号：US20130281520A1

  公开（公告）日：2013-10-24

  The present invention is directed to methods for treating metabolic disorders with compounds that are conjugates. The conjugates of the present invention are comprised of salicylic acid, triflusal, diflusinal, salsalate, IMD-0354, ibuprofen, diclofenac, licofelone, or HTB, and one or more antioxidants.

  本发明涉及使用化合物共轭物治疗代谢性疾病的方法。本发明的共轭物由水杨酸、三氟沙利、二氟沙利、水杨酸盐、IMD-0354、布洛芬、双氯芬酸、利可芬、或HTB以及一种或多种抗氧化剂组成。
• NOVEL CURCUMIN ANALOGUES AND USES THEREOF
  申请人：Lee Kuo-Hsiung

  公开号：US20080161391A1

  公开（公告）日：2008-07-03

  The present invention relates to compounds capable of acting as androgen receptor antagonists, pharmaceutical formulations containing the same, and methods of use thereof. Such uses include, but are not limited to, use as antitumor agents, particularly for the treatment of cancers such as colon, skin and prostate cancer and to induce androgen receptor antagonist activity in a subject afflicted with an androgen-related affliction. Examples of androgen-related afflictions include, but are not limited to, baldness, hirsutism, behavioral disorders, acne, and uninhibited spermatogenesis wherein inhibition of spermatogenesis is so desired.

  本发明涉及能够作为雄激素受体拮抗剂的化合物、含有该化合物的制药配方以及其使用方法。这些用途包括但不限于作为抗肿瘤剂，特别是用于治疗结肠癌、皮肤癌和前列腺癌等癌症，以及在患有雄激素相关疾病的人体内诱导雄激素受体拮抗活性。雄激素相关疾病的例子包括但不限于脱发、多毛症、行为障碍、痤疮以及需要抑制精子生成的不受抑制的精子生成。
• Influence of side-chain changes on histone deacetylase inhibitory and cytotoxicity activities of curcuminoid derivatives
  作者：La-or Somsakeesit、Thanaset Senawong、Pakit Kumboonma、Somprasong Saenglee、Arunta Samankul、Gulsiri Senawong、Chavi Yenjai、Chanokbhorn Phaosiri

  DOI：10.1016/j.bmcl.2020.127171

  日期：2020.6

  Using curcuminoids as lead compounds, fifty-nine curcuminoid derivatives with different side chains at the phenolic moiety were synthesized. All compounds were investigated for their histone deacetylase (HDAC) inhibitory activities. The potent pan-HDAC inhibitors were further tested against three human cancer cell lines including Hela, HCT116 and MCF-7 with MTT-based assay. The bisethylamide 4z and the mono-sec-butyl derivative 5j manifested good antiproliferative activities against HCT116 cancer cells with the IC50 values as 14.60 +/- 1.19 mu g/mL and 7.33 +/- 0.98 mu g/mL, respectively. Molecular docking study of both compounds with Class I HDACs revealed that the compounds might bind tightly to the binding pocket of HDAC2. These findings suggested that these compounds can be putative candidates for the development of anticancer drugs via inhibiting HDACs.
• Antitumor Agents. 217. Curcumin Analogues as Novel Androgen Receptor Antagonists with Potential as Anti-Prostate Cancer Agents
  作者：Hironori Ohtsu、Zhiyan Xiao、Junko Ishida、Masahiro Nagai、Hui-Kang Wang、Hideji Itokawa、Ching-Yuan Su、Charles Shih、Tzuying Chiang、Eugene Chang、Lee、Meng-Yin Tsai、Chawnshang Chang、Kuo-Hsiung Lee

  DOI：10.1021/jm020200g

  日期：2002.11.1

  A number of curcumin analogues were prepared and evaluated as potential androgen receptor antagonists against two human prostate cancer cell lines, PC-3 and DU-145, in the presence of androgen receptor (AR) and androgen receptor coactivator, ARA70. Compounds 4 [5-hydroxy-1,7-bis(3,4-dimethoxyphenyl)-1,4,6-heptatrien-3-one], 20 [5-hydroxy-1,7-bis[3-methoxy-4-(meth-oxycarbonylmethoxy)phenyl]-1,4,6-heptatrien-3-one], 22 [7-(4-hydroxy-3-methoxyphenyl)-4-[3(4-hydroxy-3-methoxyphenyl)acryloyl]-5-oxohepta-4,6-dienoic acid ethyl ester], 23 [7-(4-hydroxy-3-methoxyphenyl)-4-[3-(4-hydroxy-3-methoxyphenyl)acryloyl]5-oxohepta-4,6-dienoic acid], and 39 [bis(3,4-dimethoxyphenyl)-1,3-propanedione] showed potent antiandrogenic activities and were superior to hydroxyflutamide, which is the currently available antiandrogen for the treatment of prostate cancer. Structure-activity relationship (SAR) studies indicated that the bis(3,4-dimethoxyphenyl) moieties, the conjugated beta-diketone moiety, and the intramolecular symmetry of the molecules seem to be important factors related to antiandrogenic activity. The data further suggest that the coplanarity of the beta-diketone moiety and the presence of a strong hydrogen bond donor group were also crucial for the antiandrogenic activity, which is consistent with previous SAR results for hydroxyflutamide analogues. When the pharmacophoric elements of dihydrotestosterone (DHT) and compound 4 are superposed, the resulting construct implies that the curcumin analogues may function as a 17alpha-substituted DHT. Compounds 4, 20, 22, 23, and 39 have been identified as a new class of antiandrogen agents, and these compounds or their new synthetic analogues could be developed into clinical trial candidates to control androgen receptor-mediated prostate cancer growth.