3-hydroxy-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione | 159109-13-4

• 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: 3-hydroxy-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione
• 英文别名: 2-hydroxy-3-(3-indolyl)maleimide；3-hydroxy-4-(indol-3-yl)-pyrrole-2,5-dione；3-hydroxy-4-(1H-indol-3-yl)pyrrole-2,5-dione
• CAS: 159109-13-4
• 化学式: C₁₂H₈N₂O₃
• 分子量: 228.207
• InChiKey: JUUOPFPXRXKRCD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  82.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-hydroxy-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione 在 ammonium hydroxide 、 高氯酸 作用下， 以 乙醇 为溶剂， 反应 3.5h， 生成 5-methylindolo<2,3-c:3,4-e>pyrrolopyridine-1,3-(2H)-dione
  参考文献：
  名称：

  Bogza, S. L.; Nikolyukin, Yu. A.; Zubritskii, M. Yu., Russian Journal of Organic Chemistry, 1993, vol. 29, # 7.2, p. 1230 - 1233

  摘要：

  DOI：
• 作为产物：
  描述：

  ethyl 3-cyano-2-oxo-3-(3-indolyl)propionate 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 0.75h， 以85%的产率得到3-hydroxy-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  Bogza, S. L.; Nikolyukin, Yu. A.; Zubritskii, M. Yu., Russian Journal of Organic Chemistry, 1993, vol. 29, # 7.2, p. 1230 - 1233

  摘要：

  DOI：

文献信息

• Structure-Activity Relationship Refinement and Further Assessment of Indole-3-glyoxylamides as a Lead Series against Prion Disease
  作者：Mark J. Thompson、Jennifer C. Louth、Steven Ferrara、Fiona J. Sorrell、Benjamin J. Irving、Edward J. Cochrane、Anthony J. H. M. Meijer、Beining Chen

  DOI：10.1002/cmdc.201000383

  日期：2011.1.3

  indole‐3‐glyoxylamide series of antiprion agents have been explored further, resulting in discovery of several new compounds demonstrating excellent activity in a cell line model of prion disease (EC50 <10 nM). After examining a range of substituents at the para‐position of the N‐phenylglyoxylamide moiety, five‐membered heterocycles containing at least two heteroatoms were found to be optimal for the antiprion effect

  进一步研究了吲哚-3-乙醛酰胺系列抗pr病毒剂之间的结构活性关系，从而发现了几种在compounds病毒疾病细胞系模型中表现出优异活性的新化合物（EC 50 <10 n M）。在检查N的对位上的一系列取代基后苯乙醛基乙酰胺部分中，含有至少两个杂原子的五元杂环被认为是抗pr病毒作用的最佳选择。尽管没有很好的耐受性，但进行了许多修饰以探讨乙醛酰胺亚结构的重要性。然而，最有效的化合物确实对微粒体代谢具有很大的稳定性，并且最活跃的文库成员在单次给药后无限期地治愈了瘙痒病感染的细胞。因此，目前的结果证实了吲哚-3-乙氧基乙酰胺是有前途的铅系列，可用于继续进行体外和体内抗病毒疾病的评估。
• DISUBSTITUTED MALEIMIDE COMPOUNDS AND MEDICINAL UTILIZATION THEREOF
  申请人：Japan Tobacco Inc.

  公开号：EP1120414A1

  公开（公告）日：2001-08-01

  The present invention relates to a disubstituted maleimide compound of the formula [I] wherein R1 is hydrogen or alkyl, R2 is aryl, cycloalkyl or heterocyclic group, R3, R5, R6, R7 and R8 are hydrogen, halogen, hydroxyl group, amino, alkyl or alkoxy, and R4 is W or R4 and R3, or R4 and R5 jointly form a ring having a substituent W on the ring wherein W is - (CH2)l- (Y)m- (CH2)n-Z, or a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing this compound, and a protein kinase C (PKC) β inhibitor. The compounds of the present invention selectively inhibit PKCβ, and can be safe and effective pharmaceutical or prophylactic agents against the diseases caused by PKC including diabetic complications.

  本发明涉及一种二取代马来酰亚胺化合物，其化学式为[I]，其中R1为氢或烷基，R2为芳基、环烷基或杂环基，R3、R5、R6、R7和R8为氢、卤素、羟基、氨基、烷基或烷氧基，R4为W或R4和R3，或R4和R5共同形成具有环上取代基W的环，其中W为-(CH2)l-(Y)m-(CH2)n-Z，或其药学上可接受的盐，含有该化合物的药物组合物，以及蛋白激酶C（PKC）β抑制剂。本发明的化合物选择性地抑制PKCβ，并可作为安全有效的药物或预防剂用于对抗由PKC引起的疾病，包括糖尿病并发症。
• Neuroprotective and anti-proliferative compounds
  申请人：——

  公开号：US20040102467A1

  公开（公告）日：2004-05-27

  This invention features ring-substituted pyrrolo-&bgr;-carboline derivatives and ring-substitution and structural derivatives of 3-(1H-indol-3-yl)-1H-pyrrole-2,5-dione of formulas (I-III), which are useful as neuroprotective and anti-proliferative compounds. Also disclosed are methods for the preparation of these compounds, selected biological profiles and uses of these compounds in the treatment of various neurodegenerative and inflammatory diseases of the human nervous system and in the treatment of various other proliferative disorders characterized by loss of growth or cellular differentiation control including, but not limited to, cancer and inflammation. 1

  这项发明涉及环取代吡咯β-咔啉衍生物和3-(1H-吲哚-3-基)-1H-吡咯-2,5-二酮的环取代和结构衍生物，其作为神经保护和抗增殖化合物具有用途。还公开了这些化合物的制备方法，选择的生物学特性以及这些化合物在治疗人类神经系统的各种神经退行性和炎症性疾病以及治疗其他各种增殖性疾病中的用途，这些疾病的特征是失去生长或细胞分化控制，包括但不限于癌症和炎症。
• Synthesis of anilino-monoindolylmaleimides as potent and selective PKCβ inhibitors
  作者：Masahiro Tanaka、Shoichi Sagawa、Jun-ichi Hoshi、Fumito Shimoma、Isamu Matsuda、Kenji Sakoda、Tomohiko Sasase、Masanori Shindo、Takashi Inaba

  DOI：10.1016/j.bmcl.2004.07.061

  日期：2004.10

  We report herein synthesis of PKCbeta-selective inhibitors possessing the novel pharmacophore of anilino-monoindolylmalcimide. Several compounds of this series exhibited IC50's as low as 50nM against human PKCbeta2. One of the most potent compounds, 61, inhibited PKCbeta1 and PKCbeta2 with IC50 of 21 and 5nM, respectively, and exhibited selectivity of more than 60-fold in favor of PKCbeta2 relative to other PKC isozymes (PKCalpha, PKCgamma, and PKCepsilon). (C) 2004 Elsevier Ltd. All rights reserved.
• Anilino-monoindolylmaleimides as potent and selective JAK3 inhibitors
  作者：Mark E. McDonnell、Haiyan Bian、Jay Wrobel、Garry R. Smith、Shuguang Liang、Haiching Ma、Allen B. Reitz

  DOI：10.1016/j.bmcl.2014.01.001

  日期：2014.2

  We designed a series of anilino-indoylmaleimides based on structural elements from literature JAK3 inhibitors 3 and 4, and our lead 5. These new compounds were tested as inhibitors of JAKs 1, 2 and 3 and TYK2 for therapeutic intervention in rheumatoid arthritis (RA). Our requirements, based on current scientific rationale for optimum efficacy against RA with reduced side effects, was for potent, mixed JAK1 and 3 inhibition, and selectivity over JAK2. Our efforts yielded a potent JAK3 inhibitor 11d and its eutomer 11e. These compounds were highly selective for inhibition of JAK3 over JAK2 and TYK. The compounds displayed only modest JAK1 inhibition. (C) 2014 Elsevier Ltd. All rights reserved.