8,8-dipropyldihydroberberine | 1244023-76-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 原小檗碱生物碱及其衍生物
• 英文名称: 8,8-dipropyldihydroberberine
• 英文别名: 16,17-Dimethoxy-14,14-dipropyl-5,7-dioxa-13-azapentacyclo[11.8.0.02,10.04,8.015,20]henicosa-1(21),2,4(8),9,15(20),16,18-heptaene
• CAS: 1244023-76-4
• 化学式: C₂₆H₃₁NO₄
• 分子量: 421.536
• InChiKey: BFKUXKRLSDTRJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  40.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8,8-dipropyldihydroberberine 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 生成 8,8-dipropyldihydroberberine hydrochloride
  参考文献：
  名称：

  8,8-Dimethyldihydroberberine with improved bioavailability and oral efficacy on obese and diabetic mouse models

  摘要：

  The clinical use of the natural alkaloid berberine (BBR) as an antidiabetic reagent is limited by its poor bioavailability. Our previous work demonstrated that dihydroberberine (dhBBR) has enhanced bioavailability and in vivo efficacy compared with berberine. Here we synthesized the 8,8-dimethyldihydroberberine (Di-Me) with improved stability, and bioavailability over dhBBR. Similar to BBR and dhBBR, Di-Me inhibited mitochondria respiration, increased AMP:ATP ratio, activated AMPK and stimulated glucose uptake in L6 myotubes. In diet-induced obese (DIO) mice, Di-Me counteracted the increased adiposity, tissue triglyceride accumulation and insulin resistance, and improved glucose tolerance at a dosage of 15 mg/kg. Administered to db/db mice with a dosage of 50 mg/kg, Di-Me effectively reduced random fed and fasting blood glucose, improved glucose tolerance, alleviated insulin resistance and reduced plasma triglycerides, with better efficacy than dhBBR at the same dosage. Our work highlights the importance of dihydroberberine analogs as potential therapeutic reagents for type 2 diabetes treatment. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.085
• 作为产物：
  描述：

  小檗浸碱 在 三氯氧磷 作用下， 以 乙醚 、 水 为溶剂， 反应 5.0h， 生成 8,8-dipropyldihydroberberine
  参考文献：
  名称：

  8,8-Dialkyldihydroberberines with Potent Antiprotozoal Activity

  摘要：

  Semisynthetic 8,8-dialkyldihydroberberines (8,8-DDBs) were found to possess mid- to low-nanomolar potency against Plasmodium falciparum blood-stage parasites, Leishmania donovani intracellular amastigotes, and Trypanosoma brucei brucei bloodstream forms. For example, 8,8-diethyldihydroberberine chloride (5b) exhibited in vitro IC50 values of 77, 100, and 5.3 nM against these three parasites, respectively. In turn, two 8,8-dialkylcanadines, obtained by reduction of the corresponding 8,8-DDBs, were much less potent against these parasites in vitro. While the natural product berberine is a weak DNA binder, the 8,8-DDBs displayed no affinity for DNA, as assessed by changes in the melting temperature of poly(dA.dT) DNA. Selected 8,8-DDBs showed efficacy in mouse models of visceral leishmaniasis and African trypanosomiasis, with 8,8-dimethyldihydroberberine chloride (5a) reducing liver parasitemia by 46% in L. donovani-infected BALB/c mice when given at an intraperitoneal dose of 10 mg/kg/day for five days. The 8,8-DDBs may thus serve as leads for discovering new antimalarial, antileishmanial, and antitrypanosomal drug candidates.

  DOI：

  10.1021/np300638f

文献信息

• 8,8-Dimethyldihydroberberine with improved bioavailability and oral efficacy on obese and diabetic mouse models
  作者：Zhe Cheng、An-Feng Chen、Fang Wu、Li Sheng、Han-Kun Zhang、Min Gu、Yuan-Yuan Li、Li-Na Zhang、Li-Hong Hu、Jing-Ya Li、Jia Li

  DOI：10.1016/j.bmc.2010.06.085

  日期：2010.8

  The clinical use of the natural alkaloid berberine (BBR) as an antidiabetic reagent is limited by its poor bioavailability. Our previous work demonstrated that dihydroberberine (dhBBR) has enhanced bioavailability and in vivo efficacy compared with berberine. Here we synthesized the 8,8-dimethyldihydroberberine (Di-Me) with improved stability, and bioavailability over dhBBR. Similar to BBR and dhBBR, Di-Me inhibited mitochondria respiration, increased AMP:ATP ratio, activated AMPK and stimulated glucose uptake in L6 myotubes. In diet-induced obese (DIO) mice, Di-Me counteracted the increased adiposity, tissue triglyceride accumulation and insulin resistance, and improved glucose tolerance at a dosage of 15 mg/kg. Administered to db/db mice with a dosage of 50 mg/kg, Di-Me effectively reduced random fed and fasting blood glucose, improved glucose tolerance, alleviated insulin resistance and reduced plasma triglycerides, with better efficacy than dhBBR at the same dosage. Our work highlights the importance of dihydroberberine analogs as potential therapeutic reagents for type 2 diabetes treatment. (C) 2010 Elsevier Ltd. All rights reserved.
• 8,8-Dialkyldihydroberberines with Potent Antiprotozoal Activity
  作者：Molla Endeshaw、Xiaohua Zhu、Shanshan He、Trupti Pandharkar、Emily Cason、Kiran V. Mahasenan、Hitesh Agarwal、Chenglong Li、Manoj Munde、W. David Wilson、Mark Bahar、Raymond W. Doskotch、A. Douglas Kinghorn、Marcel Kaiser、Reto Brun、Mark E. Drew、Karl A. Werbovetz

  DOI：10.1021/np300638f

  日期：2013.3.22

  Semisynthetic 8,8-dialkyldihydroberberines (8,8-DDBs) were found to possess mid- to low-nanomolar potency against Plasmodium falciparum blood-stage parasites, Leishmania donovani intracellular amastigotes, and Trypanosoma brucei brucei bloodstream forms. For example, 8,8-diethyldihydroberberine chloride (5b) exhibited in vitro IC50 values of 77, 100, and 5.3 nM against these three parasites, respectively. In turn, two 8,8-dialkylcanadines, obtained by reduction of the corresponding 8,8-DDBs, were much less potent against these parasites in vitro. While the natural product berberine is a weak DNA binder, the 8,8-DDBs displayed no affinity for DNA, as assessed by changes in the melting temperature of poly(dA.dT) DNA. Selected 8,8-DDBs showed efficacy in mouse models of visceral leishmaniasis and African trypanosomiasis, with 8,8-dimethyldihydroberberine chloride (5a) reducing liver parasitemia by 46% in L. donovani-infected BALB/c mice when given at an intraperitoneal dose of 10 mg/kg/day for five days. The 8,8-DDBs may thus serve as leads for discovering new antimalarial, antileishmanial, and antitrypanosomal drug candidates.