dimethyl-tetrahydrocurcumin | 55094-78-5

• 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: dimethyl-tetrahydrocurcumin
• 英文别名: dimethylcurcumin；di-O-methyltetrahydrocurcumin；Di-O-Methylhexahydrocurcumin；1,7-bis(3,4-dimethoxyphenyl)heptane-3,5-dione
• CAS: 55094-78-5
• 化学式: C₂₃H₂₈O₆
• 分子量: 400.472
• InChiKey: UPAMFNILWFQMHT-UHFFFAOYSA-N

物化性质

• 熔点：
  72-73 °C
• 沸点：
  527.2±45.0 °C(Predicted)
• 密度：
  1.125±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  dimethyl-tetrahydrocurcumin 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 生成 (+/-)-di-O-methyl hexahydrocurcumin
  参考文献：
  名称：

  Curcuminoid analogs with potent activity against Trypanosoma and Leishmania species

  摘要：

  The natural curcuminoids curcumin (1), demethoxycurcumin (2) and bisdemethoxycurcumin (3) have been chemically modified to give 46 analogs and 8 pairs of 1: 1 mixture of curcuminoid analogs and these parent curcuminoids and their analogs were assessed against protozoa of the Tryponosoma and Leishmania species. The parent curcuminoids exhibited low antitrypanosomal activity (EC50 for our drug-sensitive Trypanosoma brucei brucei line (WT) of compounds 1, 2 and 3 are 2.5, 4.6 and 7.7 mu M, respectively). Among 43 curcuminoid analogs and 8 pairs of 1: 1 mixture of curcuminoid analogs tested, 8 pure analogs and 5 isomeric mixtures of analogs exhibited high antitrypanosomal activity in sub-micromolar order of magnitude. Among these highly active analogs, 1,7-bis(4-hydroxy-3-methoxy-phenyl)hept-4-en-3-one (40) was the most active compound, with an EC50 value of 0.053 +/- 0.007 mu M; it was about 2-fold more active than the standard veterinary drug diminazene aceturate (EC50 0.12 +/- 0.01 mu M). Using a previously characterized diminazene-resistant T. b, brucei (TbAT1-KO) and a derived multi-drug resistant line (B48), no cross-resistance of curcuminoids was observed to the diamidine and melaminophenyl arsenical drugs that are the current treatments. Indeed, curcuminoids carrying a conjugated keto (enone) motif, including 40, were significantly more active against 7: b. brucei B48. This enone motif was found to contribute to particularly high trypanocidal activity against all Trypanosoma species and strains tested. The parent curcuminoids showed low antileishmanial activity (EC50 values of compounds 1 and 2 for Leishmania mexicana amastigotes are 16 +/- 3 and 37 +/- 6 mu M. respectively) while the control drug, pentamidine, displayed an EC50 of 16 +/- 2 mu M. Among the active curcuminoid analogs, four Compounds exhibited EC50 values of less than 5 mu M against Leishmania major promastigotes and four against L mexicana amastigotes. No significant difference in sensitivity to curcuminoids between L. major promastigotes and L. mexicana amastigotes was observed. The parent curcuminoids and most of their analogs were also tested for their toxicity against human embryonic kidney (HEK) cells. All the curcuminoids exhibited lower toxicity to HEK cells than to T b. brucei bloodstream forms and only one of the tested compounds showed significantly higher activity against HEK cells than curcumin (1). The selectivity index for T b. brucei ranged from 3-fold to 1500-fold. The selectivity index for the most active analog, the enone 40, was 453-fold. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.11.035
• 作为产物：
  描述：

  二甲氧基姜黄素 在 platinum(IV) oxide 氢气 作用下， 以52%的产率得到dimethyl-tetrahydrocurcumin
  参考文献：
  名称：

  β-二酮部分参与四氢姜黄素的抗氧化机制。

  摘要：

  我们研究了姜黄素和姜黄素的主要代谢产物之一四氢姜黄素（THC）对叔丁基过氧化氢诱导的红细胞膜重影的脂质过氧化的抑制作用。结果表明，四氢大麻酚显示出比姜黄素更大的抑制作用。为了研究抗氧化活性的机制，我们检查了几种抑制剂的作用，例如抗氧化剂，羟基自由基清除剂，1O2猝灭剂和金属离子螯合剂。考虑到所有抑制剂均不能抑制膜过氧化，因此THC必须清除自由基，例如叔丁氧基和过氧基。为了阐明THC的抗氧化机理，特别是β-二酮部分的作用，将二甲基化的THC与由2,2'-偶氮双（2，4-二甲基戊腈）。检测到四个氧化产物，其中三个被鉴定为3,4-二甲氧基苯甲酸，3'，4'-二甲氧基苯乙酮和3-（3,4-二甲氧基苯基）-丙酸。第四氧化产物似乎是不稳定的中间体，尚未确定其详细结构。这些结果表明，THC的β-二酮部分必须通过在β-二酮部分中的两个羰基之间的活性亚甲基碳上的CC键的裂解来显示抗氧化活性。由于四氢大麻酚是

  DOI：

  10.1016/0006-2952(96)00302-4

文献信息

• Involvement of the β-diketone moiety in the antioxidative Mechanism of Tetrahydrocurcumin
  作者：Yosunori Sugiyama、Shunro Kawakishi、Toshihiko Osawa

  DOI：10.1016/0006-2952(96)00302-4

  日期：1996.8

  the beta-diketone moiety of THC must exhibit antioxidative activity by cleavage of the C-C bond at the active methylene carbon between two carbonyls in the beta-diketone moiety. Because THC is one of the major metabolites of curcumin, it may also exhibit the same physiological and pharmacological properties as the active form of curcumin in vivo by means of the beta-diketone moiety as well as phenolic

  我们研究了姜黄素和姜黄素的主要代谢产物之一四氢姜黄素（THC）对叔丁基过氧化氢诱导的红细胞膜重影的脂质过氧化的抑制作用。结果表明，四氢大麻酚显示出比姜黄素更大的抑制作用。为了研究抗氧化活性的机制，我们检查了几种抑制剂的作用，例如抗氧化剂，羟基自由基清除剂，1O2猝灭剂和金属离子螯合剂。考虑到所有抑制剂均不能抑制膜过氧化，因此THC必须清除自由基，例如叔丁氧基和过氧基。为了阐明THC的抗氧化机理，特别是β-二酮部分的作用，将二甲基化的THC与由2,2'-偶氮双（2，4-二甲基戊腈）。检测到四个氧化产物，其中三个被鉴定为3,4-二甲氧基苯甲酸，3'，4'-二甲氧基苯乙酮和3-（3,4-二甲氧基苯基）-丙酸。第四氧化产物似乎是不稳定的中间体，尚未确定其详细结构。这些结果表明，THC的β-二酮部分必须通过在β-二酮部分中的两个羰基之间的活性亚甲基碳上的CC键的裂解来显示抗氧化活性。由于四氢大麻酚是
• 姜黄素衍生物的用途
  申请人：中国科学院成都生物研究所

  公开号：CN110327315A

  公开（公告）日：2019-10-15

  本发明提供了姜黄素衍生物的用途。具体提供了式Ⅰ所示姜黄衍生物，或其盐在制备抗炎性疾病的药物和/或COX抑制剂的用途。本发明姜黄素衍生物具有良好COX抑制活性和抗炎活性，可用于制备COX抑制剂和抗炎药物。其中，化合物6和化合物7对于COX‑2抑制活性和抗炎活性的效果最优。可用于制备COX‑2抑制剂和抗炎药物。
• Chemosensory receptor ligand-based therapies
  申请人：Anji Pharma (US) LLC

  公开号：US10610500B2

  公开（公告）日：2020-04-07

  Provided herein are methods for treating conditions associated with a chemosensory receptor, including diabetes, obesity, and other metabolic diseases, disorders or conditions by administrating a composition comprising a chemosensory receptor ligand, such as a bitter receptor ligand. Also provided herein are chemosensory receptor ligand compositions, including bitter receptor ligand compositions, and methods for the preparation thereof for use in the methods of the present invention. Also provided herein are compositions comprising metformin and salts thereof and methods of use.

  本文提供了通过施用包含化感受体配体（如苦味受体配体）的组合物来治疗与化感受体相关的病症（包括糖尿病、肥胖症和其他代谢性疾病、失调或病症）的方法。本文还提供了化学感觉受体配体组合物，包括苦味受体配体组合物，及其用于本发明方法的制备方法。本文还提供了包含二甲双胍及其盐类的组合物和使用方法。
• 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.
• CHEMOSENSORY RECEPTOR LIGAND-BASED THERAPIES
  申请人：Anji Pharma (US) LLC

  公开号：EP2661266B1

  公开（公告）日：2020-09-16