2-(5-formyl-2,4-dimethyl-1H-pyrrol-3-yl)ethyl morpholin-4-yl ketone | 1574491-37-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(5-formyl-2,4-dimethyl-1H-pyrrol-3-yl)ethyl morpholin-4-yl ketone
• 英文别名: 3,5-dimethyl-4-(3-morpholin-4-yl-3-oxo-propyl)-1H-pyrrole-2-carbaldehyde；3,5-dimethyl-4-(3-morpholin-4-yl-3-oxopropyl)-1H-pyrrole-2-carbaldehyde
• CAS: 1574491-37-4
• 化学式: C₁₄H₂₀N₂O₃
• 分子量: 264.324
• InChiKey: CXKBECSDTKMNPQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  62.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(3-chloro-4-fluoro-phenylamino)-5,7-dihydro-pyrrolo[2,3-d]pyrimidin-6-one 、 2-(5-formyl-2,4-dimethyl-1H-pyrrol-3-yl)ethyl morpholin-4-yl ketone 在 哌啶 乙醇 作用下， 以 乙醇 为溶剂， 反应 72.0h， 生成 4-(3-Chloro-4-fluoro-phenylamino)-5-[3,5-dimethyl-4-(3-morpholin-4-yl-3-oxo-propyl)-1H-pyrrol-2-ylmethylene]-5,7-dihydro-pyrrolo[2,3-D]pyrimidin-6-one
  参考文献：
  名称：

  4-substituted 7-AZA-indolin-2-ones and their use as protein kinase inhibitors

  摘要：

  本发明涉及4-取代的7-氮杂吲哚-2-酮及其作为蛋白激酶抑制剂的用途。本文所披露的特定的4-取代的7-氮杂吲哚-2-酮为式1及其药学上可接受的盐、溶剂合物、包合物和前药，其中R1、R2、R3、R4、X、Y和Z在此定义。本发明还涉及包含式1化合物的制药组合物和剂型，以及其用于治疗和/或预防癌症等疾病的方法，但不限于此。

  公开号：

  US06908930B2
• 作为产物：
  描述：

  吗啉 、 3-(2,4-二甲基-5-醛基-1H-吡咯)-3-丙酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 2-(5-formyl-2,4-dimethyl-1H-pyrrol-3-yl)ethyl morpholin-4-yl ketone
  参考文献：
  名称：

  Novel acylureidoindolin-2-one derivatives as dual Aurora B/FLT3 inhibitors for the treatment of acute myeloid leukemia

  摘要：

  A series of 6-acylureido derivatives containing a 3-(pyrrol-2-ylmethylidene)indolin-2-one scaffold were synthesized as potential dual Aurora B/FLT3 inhibitors by replacing the 6-arylureido moiety in 6-arylureidoindolin-2-one-based multi-kinase inhibitors. (Z)-N-(2-(pyrrolidin-l-yl)ethyl)-5-((6-(3-(2-fluoro-4-methoxybenzoyflureido)-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide (54) was identified as a dual Aurora B/FLT3 inhibitor (IC50 = 0.4 nM and 0.5 nM, respectively). Compound 54 also exhibited potent cytotoxicity with single-digit nanomolar IC50 values against the FLT3 mutant-associated human acute myeloid leukemia (AML) cell lines MV4-11 (FLT3-ITD) and MOLM-13 (FLT3-ITD). Compound 54 also specifically induced extrinsic apoptosis by inhibiting the phosphorylation of the Aurora B and FLT3 pathways in MOLM-13 cells. Compound 54 had a moderate pharmacokinetic profile. The mesylate salt of 54 efficiently inhibited tumor growth and reduced the mortality of BALB/c nude mice (subcutaneous xenograft model) that had been implanted with AML MOLM-13 cells. Compound 54 is more potent than sunitinib not only against FLT3-WT AML cells but also active against sunitinib-resistant FLT3-ITD AML cells. This study demonstrates the significance of dual Aurora B/FLT3 inhibitors for the development of potential agents to treat AML. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.07.108

文献信息

• 4-substituted 7-aza-indolin-2-ones and their use as protein kinase inhibitors
  申请人：——

  公开号：US20020183319A1

  公开（公告）日：2002-12-05

  This invention relates to 4-substituted 7-aza-indolin-2-ones and their use as protein kinase inhibitors. Particular 4-substituted 7-aza-indolin-2-ones disclosed herein are of Formula 1 1 and pharmaceutically acceptable salts, solvates, clathrates, and prodrugs thereof, wherein R 1 , R 2 , R 3 , R 4 , X, Y, and Z are defined herein. The invention fuirther relates to pharmaceutical compositions and dosage forms comprising compounds of Formula 1 and to methods of their use for the treatment and/or prevention of diseases such as, but not limited to, cancer.

  该发明涉及4-取代的7-氮杂吲哚-2-酮及其作为蛋白激酶抑制剂的用途。本文披露的特定4-取代的7-氮杂吲哚-2-酮属于第11式和其药学上可接受的盐、溶剂合物、包合物和前药，其中R1、R2、R3、R4、X、Y和Z在此定义。该发明还涉及包含第1式化合物的药物组合物和剂型，以及其用于治疗和/或预防癌症等疾病的方法。
• [EN] 4-SUBSTITUTED 7-AZA-INDOLIN-2-ONES AND THEIR USE AS PROTEIN KINASE INHIBITORS<br/>[FR] 7-AZA-INDOLINE-2-ONES SUBSTITUES EN 4 ET LEUR UTILISATION COMME INHIBITEURS DE PROTEINE KINASE
  申请人：SUGEN INC

  公开号：WO2001046196A1

  公开（公告）日：2001-06-28

  This invention relates to 4-substituted 7-aza-indolin-2-ones and their use as protein kinase inhibitors. Particular 4-substituted 7-aza-indolin-2-ones disclosed herein are of formula (1) and pharmaceuitaclly acceptable salts, solvates, clathrates, and prodrugs thereof, wherein R1, R2, R3, R4, X, Y, and Z are defined herein. The invention further relates to pharmaceutical compositions and dosage forms comprising compounds of formula (1) and to methods of their use for the treatment and/or prevention of diseases such as, but not limited to, cancer.

  本发明涉及4-取代的7-氮杂吲哚-2-酮及其作为蛋白激酶抑制剂的用途。特别是，在此披露的4-取代的7-氮杂吲哚-2-酮的公式（1）及其药物可接受的盐，溶剂合物，包合物和前药，其中R1，R2，R3，R4，X，Y和Z在此定义。本发明还涉及包含公式（1）化合物的制药组合物和剂型，以及它们用于治疗和/或预防癌症等疾病的方法，但不限于此。
• 4-Substituted 7-aza-indolin-2-ones and their use as protein kinase inhibitors
  申请人：SUGEN, INC.

  公开号：US20040053924A1

  公开（公告）日：2004-03-18

  This invention relates to 4-substituted 7-aza-indolin-2-ones and their use as protein kinase inhibitors. Particular 4-substituted 7-aza-indolin-2-ones disclosed herein are of Formula 1 1 and pharmaceutically acceptable salts, solvates, clathrates, and prodrugs thereof, wherein R 1 , R 2 , R 3 , R 4 , X, Y, and Z are defined herein. The invention further relates to pharmaceutical compositions and dosage forms comprising compounds of Formula 1 and to methods of their use for the treatment and/or prevention of diseases such as, but not limited to, cancer.

  本发明涉及4-取代的7-氮杂吲哚-2-酮及其作为蛋白激酶抑制剂的用途。本文披露的特定4-取代的7-氮杂吲哚-2-酮属于公式11和其药学上可接受的盐、溶剂合物、包合物和前药，其中R1、R2、R3、R4、X、Y和Z在此定义。本发明还涉及包含公式1化合物的制药组合物和剂型，以及其用于治疗和/或预防癌症等疾病的方法。
• 4-SUBSTITUTED 7-AZA-INDOLIN-2-ONES AND THEIR USE AS PROTEIN KINASE INHIBITORS
  申请人：Sugen, Inc.

  公开号：EP1244672A1

  公开（公告）日：2002-10-02
• US6610688B2
  申请人：——

  公开号：US6610688B2

  公开（公告）日：2003-08-26