3-[1-(3-hydroxypropyl)-1H-indol-3-yl]-4-(phenylamino)-1H-pyrrole-2,5-dione | 257878-84-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-[1-(3-hydroxypropyl)-1H-indol-3-yl]-4-(phenylamino)-1H-pyrrole-2,5-dione
• 英文别名: 3-[1-(3-Hydroxy-propyl)-1H-indol-3-yl]-4-phenylamino-pyrrole-2,5-dione；3-anilino-4-[1-(3-hydroxypropyl)indol-3-yl]pyrrole-2,5-dione
• CAS: 257878-84-5
• 化学式: C₂₁H₁₉N₃O₃
• 分子量: 361.4
• InChiKey: APGXSWCOZAHJDR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  83.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[1-(3-hydroxypropyl)-1H-indol-3-yl]-4-(phenylamino)-1H-pyrrole-2,5-dione 在 N-溴代丁二酰亚胺(NBS) 、 sodium hydride 、 三苯基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-(phenylamino)-4-(1-(3-pyrrolidin-1-ylpropyl)-1H-indol-3-yl]-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  Synthesis of anilino-monoindolylmaleimides as potent and selective PKCβ inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2004.07.061
• 作为产物：
  描述：

  3-吲哚乙酰胺 在 potassium tert-butylate 、 四丁基氟化铵 、 sodium hydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-[1-(3-hydroxypropyl)-1H-indol-3-yl]-4-(phenylamino)-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  Synthesis of anilino-monoindolylmaleimides as potent and selective PKCβ inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2004.07.061

文献信息

• 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。
• [EN] SELECTIVE KINASE INHIBITORS<br/>[FR] INHIBITEURS SÉLECTIFS DE KINASE
  申请人：REACTION BIOLOGY CORP

  公开号：WO2013029043A1

  公开（公告）日：2013-02-28

  The present invention relates to methods of modulating (for example, inhibiting) activity of JAK3, comprising contacting the JAK3 with a compound of Formula I: or pharmaceutically acceptable salt thereof, wherein constituent members are provided hereinwith. The present invention further provides novel methods of use of the same as JAK3 inhibitors in the treatment of JAK3 -associated diseases including, for example, inflammatory and autoimmune disorders.
• 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.