(Z)-5-bromo-1,3-dihydro-3-[(1H-pyrrol-2-yl)methylene]-2H-indol-2-one | 276884-13-0

• 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: (Z)-5-bromo-1,3-dihydro-3-[(1H-pyrrol-2-yl)methylene]-2H-indol-2-one
• 英文别名: (Z)-5-bromo-3-(1H-pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one；(3Z)-5-bromo-3-(1H-pyrrol-2-ylmethylene)-1,3-dihydro-2H-indol-2-one；5-bromo-3-(1H-pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one；5-bromo-3-[(pyrrol-2-yl)methylene]indolin-2-one；(Z)-3-((1H-pyrrol-2-yl)methylene)-5-bromoindolin-2-one；(3Z)-5-bromo-3-(1H-pyrrol-2-ylmethylidene)-1H-indol-2-one
• CAS: 276884-13-0
• 化学式: C₁₃H₉BrN₂O
• 分子量: 289.131
• InChiKey: YLCIQJHPQCQLFI-XFFZJAGNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 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：
  44.9
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (Z)-5-bromo-1,3-dihydro-3-[(1H-pyrrol-2-yl)methylene]-2H-indol-2-one 在 tris(dibenzylideneacetone)dipalladium (0) 、 三(邻甲基苯基)磷 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 5-[5-((2S)-2-Amino-3-phenyl-propoxy)-pyridin-3-yl]-3-(1H-pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one
  参考文献：
  名称：

  Syntheses of Potent, Selective, and Orally Bioavailable Indazole-Pyridine Series of Protein Kinase B/Akt Inhibitors with Reduced Hypotension

  摘要：

  Compound 7 was identified as a potent (IC50 = 14 nM), selective, and orally bioavailable (F = 70% in mouse) inhibitor of protein kinase B/Akt. While promising efficacy was observed in vivo, this compound showed effects on depolarization of Purkinje fibers in an in vitro assay and CV hypotension in vivo. Guided by an X-ray structure of 7 bound to protein kinase A, which has 80% homology with Akt in the kinase domain, our efforts have focused on structure-activity relationship (SAR) studies of the phenyl moiety, in an attempt to address the cardiovascular liability and further improve the Akt potency. A novel and efficient synthetic route toward diversely substituted phenyl derivatives of 7 was developed utilizing a copper-mediated aziridine ring-opening reaction as the key step. To improve the selectivity of these Akt inhibitors over other protein kinases, a nitrogen atom was incorporated into selected phenyl analogues of 7 at the C-6 position of the methyl indazole scaffold. These modifications resulted in the discovery of inhibitor 37c with greater potency (IC50 = 0.6 nM vs Akt), selectivity, and improved cardiovascular safety profile. The SARs, pharmacokinetic profile, and CV safety of selected Akt inhibitors will be discussed.

  DOI：

  10.1021/jm0701019
• 作为产物：
  描述：

  5-溴氧化吲哚 生成 (Z)-5-bromo-1,3-dihydro-3-[(1H-pyrrol-2-yl)methylene]-2H-indol-2-one
  参考文献：
  名称：

  Protein kinase inhibitors

  摘要：

  具有公式1或其治疗上可接受的盐的化合物是蛋白激酶抑制剂。 揭示了该化合物的制备、含有该化合物的组合物以及使用该化合物治疗疾病。

  公开号：

  US20030162785A1

文献信息

• Kinase inhibitors
  申请人：——

  公开号：US20030187026A1

  公开（公告）日：2003-10-02

  Compounds having the formula 1 are useful for inhibiting protein kinases. Also disclosed are compositions which inhibit protein kinases and methods of inhibiting protein kinases in a patient.

  具有以下化学式的化合物对抑制蛋白激酶很有用。还公开了抑制蛋白激酶的组合物以及在患者中抑制蛋白激酶的方法。
• 4-and 5-alkynyloxindoles and 4-and 5-alkenyloxindoles
  申请人：Hoffmann-La Roche Inc.

  公开号：US06313310B1

  公开（公告）日：2001-11-06

  Disclosed are 4- and 5-alkynyloxindoles as well as 4- and 5-alkenyloxindoles that inhibit or modulate protein kinases, in particular JNK protein kinases. The compounds of the invention and their pharmaceutically acceptable salts, and prodrugs of said compounds, are useful as anti-inflammatory agents, particularly useful in the treatment of rheumatoid arthritis. Also disclosed are pharmaceutical compositions containing the foregoing compounds, methods for the treatment and/or control of inflammation, particularly in the treatment or control of rheumatoid arthritis using these compounds, as well as intermediates useful in the preparation of compounds of the invention.

  揭示了作为蛋白激酶抑制剂或调节剂的4-和5-炔基氧吲哚以及4-和5-烯基氧吲哚，特别是JNK蛋白激酶。本发明的化合物及其药学上可接受的盐，以及该化合物的前药，在抗炎药物中有用，特别适用于类风湿关节炎的治疗。还公开了含有上述化合物的药物组合物，以及使用这些化合物治疗和/或控制炎症的方法，特别是在治疗或控制类风湿关节炎中使用这些化合物，以及在制备本发明化合物中有用的中间体。
• [EN] Novel Hybrid Compounds<br/>[FR] NOUVEAUX COMPOSÉS HYBRIDES
  申请人：UNIV GREENWICH

  公开号：WO2012025726A1

  公开（公告）日：2012-03-01

  This invention relates to novel hybrid compounds, of formula 1 wherein R1 to R7, L and Y are as defined herein, wherein Y denotes a histone deacetylase inhibiting moiety (such as a heterocycle, hydroxamic acid or diamine) and L denotes a linker group the invention also relates to processes for preparing them and their use as therapeutic agents and diagnostic agents.

  本发明涉及一种新型杂化化合物，其化学式为1，其中R1至R7、L和Y的定义如本文所述，其中Y表示组织脱乙酰酶抑制基团（如杂环、羟基酰胺或二胺），L表示连接基团，该发明还涉及其制备方法以及它们作为治疗剂和诊断剂的用途。
• Indolinone derivatives and their use in treating disease-states such as cancer
  申请人：Arnaiz Damian

  公开号：US20050090541A1

  公开（公告）日：2005-04-28

  Indolinone derivatives, such as compounds of the formula (I): wherein A, m, n, R 1 , R 2 , R 3 , R 5 and R 6 are described herein, are disclosed herein as being useful in treating mammal having disease-states alleviated by the inhibition of PDK-1 activity.

  Indolinone衍生物，例如公式（I）中的化合物：其中A，m，n，R1，R2，R3，R5和R6如本文所述，据本文披露，可用于治疗通过抑制PDK-1活性缓解疾病状态的哺乳动物。
• [EN] BENZOTHIOPHENE, BENZYLOXYBENZYLIDENE AND INDOLINE DERIVATIVES USEFUL FOR THE TREATMENT OF TUBERCULOSIS<br/>[FR] BENZOTHIOPHÈNE, BENZYLOXYBENZYLIDÈNE ET DÉRIVÉS DE L'INDOLINE UTILES POUR LE TRAITEMENT DE LA TUBERCULOSE
  申请人：ECOLE POLYTECH

  公开号：WO2016041972A1

  公开（公告）日：2016-03-24

  The present invention relates to benzothiophene, benzyloxybenzylidene and indoline-2-one derivatives and the use of said derivatives in the treatment and/or prevention of tuberculosis.

  本发明涉及苯并噻吩、苄氧基苯甲醛亚甲基和吲哚啉-2-酮衍生物，以及该衍生物在结核病的治疗和/或预防中的应用。