1-(3-(5-fluoro-1H-indol-3-yl)-3-(3,4,5-trimethoxyphenyl)propanoyl)-5,6-dihydropyridin-2(1H)-one | 1337905-63-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-(3-(5-fluoro-1H-indol-3-yl)-3-(3,4,5-trimethoxyphenyl)propanoyl)-5,6-dihydropyridin-2(1H)-one
• 英文别名: 1-[3-(5-fluoro-1H-indol-3-yl)-3-(3,4,5-trimethoxyphenyl)propanoyl]-2,3-dihydropyridin-6-one
• CAS: 1337905-63-1
• 化学式: C₂₅H₂₅FN₂O₅
• 分子量: 452.482
• InChiKey: WWPQWTQPRLADCU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  80.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5,6-二氢-2(1H)-吡啶酮 在 正丁基锂 、 碘 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 为溶剂， 反应 16.75h， 生成 1-(3-(5-fluoro-1H-indol-3-yl)-3-(3,4,5-trimethoxyphenyl)propanoyl)-5,6-dihydropyridin-2(1H)-one 、 1-(3-(5-fluoro-1H-indol-3-yl)-3-(3,4,5-trimethoxyphenyl)propanoyl)-4-(5-fluoro-1H-indol-3-yl)piperidin-2-one
  参考文献：
  名称：

  作为有效醛糖还原酶抑制剂 (ARI) 的新 piplartine 类似物的合成和生物学评价

  摘要：

  作为我们致力于从天然来源开发抗糖尿病药物的继续努力，从胡椒中分离出了哌拉汀，并发现它可以抑制重组人 ALR2，IC 50为 160 μM。为了提高功效，通过修饰这种天然产物先导物的苯乙烯基/芳香族和杂环官能团，合成了一系列类似物。对所有衍生物的ALR2抑制活性进行了测试，结果表明，哌拉汀与吲哚衍生物迈克尔加成制备的加合物3c 、 3e和2j表现出有效的ARI活性，而其他化合物则表现出不同程度的抑制作用。这些活性化合物还能够防止山梨醇在人红细胞中积聚。

  DOI：

  10.1016/j.ejmech.2012.09.014

文献信息

• ALR2 INHIBITORS AND THEIR SYNTHESIS FROM A NATURAL SOURCE
  申请人：Janaswamy Madhusudana Rao

  公开号：US20120245357A1

  公开（公告）日：2012-09-27

  A Michael adduct of piplartine, to provide inhibition of ALR2 in vitro (supported by molecular docking) and their potential to suppress the accumulation of sorbitol in erythrocytes when incubated under high glucose conditions; a treatment method using a Michael adduct; and a process for preparing a Michael adduct are provided.

  提供一种皮普拉丁的迈克尔加合物，用于体外抑制ALR2（通过分子对接支持），并在高葡萄糖条件下培养时抑制红细胞中山梨醇积累的潜力；提供一种使用迈克尔加合物的治疗方法；以及提供一种制备迈克尔加合物的方法。
• [EN] ALR2 INHIBITORS AND THEIR SYNTHESIS FROM A NATURAL SOURCE<br/>[FR] INHIBITEURS D'ALR2 ET LEUR SYNTHÈSE À PARTIR D'UNE SOURCE NATURELLE
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2011117706A1

  公开（公告）日：2011-09-29

  Activation of polyol pathway due to increased aldose reductase (ALR2) activity is one of the several mechanisms that have been implicated in the development of various complications of diabetes such nephropathy, neuropathy, retinopathy and cataract. Hence, inhibition of ALR2 has been considered as an effective means to prevent and treat the diabetic complications. We have shown that piplartine isolated from Piper species (Piper chaba) inhibits ALR2 activity. Use of compounds of general formula A isolated from medicinal plant Piper chaba having (Aldose reductase) ALR2 inhibitory activity and serves as a lead molecule to synthesize novel ALR2 inhibitors, wherein Ri=Hyrogen, Methyl or Benzyl; R2=Methyl or Phenyl; R3=Nitro, Fluro, Bromo, Iodo, Methyl or Methoxy; R4 is selected from wherein the representative compounds comprising synthesis of Michael adduct from naturally isolated piplartine with different substituted indoles, by using catalytic amount of molecular iodine, under selective solvent 1,2-Dichloroethane are: Mono Michael adduct 2a-c, 2f-k Di Michael adduct 3a-3k
• Synthesis and biological evaluation of new piplartine analogues as potent aldose reductase inhibitors (ARIs)
  作者：Vidadala Ramasubba Rao、Puppala Muthenna、Gundeti Shankaraiah、Chandrasekhar Akileshwari、Kothapalli Hari Babu、Ganji Suresh、Katragadda Suresh Babu、Rotte Sateesh Chandra Kumar、Kothakonda Rajendra Prasad、Potharaju Ashok Yadav、J. Mark Petrash、Geereddy Bhanuprakash Reddy、Janaswamy Madhusudana Rao

  DOI：10.1016/j.ejmech.2012.09.014

  日期：2012.11

  As a continuation of our efforts directed towards the development of anti-diabetic agents from natural sources, piplartine was isolated from Piper chaba, and was found to inhibit recombinant human ALR2 with an IC50 of 160 μM. To improve the efficacy, a series of analogues have been synthesized by modification of the styryl/aromatic and heterocyclic ring functionalities of this natural product lead

  作为我们致力于从天然来源开发抗糖尿病药物的继续努力，从胡椒中分离出了哌拉汀，并发现它可以抑制重组人 ALR2，IC 50为 160 μM。为了提高功效，通过修饰这种天然产物先导物的苯乙烯基/芳香族和杂环官能团，合成了一系列类似物。对所有衍生物的ALR2抑制活性进行了测试，结果表明，哌拉汀与吲哚衍生物迈克尔加成制备的加合物3c 、 3e和2j表现出有效的ARI活性，而其他化合物则表现出不同程度的抑制作用。这些活性化合物还能够防止山梨醇在人红细胞中积聚。