(S)-3-(1-((4-(5-(1-(2-hydroxyethyl)-1,2,3,6-tetrahydropyridin-4-yl)pyrimidin-2-yl)morpholin-2-yl)methyl)-6-oxo-1,6-dihydropyridazin-3-yl)benzonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (S)-3-(1-((4-(5-(1-(2-hydroxyethyl)-1,2,3,6-tetrahydropyridin-4-yl)pyrimidin-2-yl)morpholin-2-yl)methyl)-6-oxo-1,6-dihydropyridazin-3-yl)benzonitrile
• 英文别名: (S)-3-(1-((4-(5-(1-(2-hydroxyethyl)-1,2,3,6-tetrahydropyridin-4-yl)pyrimidin-yl)morpholin-2-yl)methyl)-6-oxo-1,6-dihydropyridazin-3-yl)benzonitrile；3-[1-[[(2S)-4-[5-[1-(2-hydroxyethyl)-3,6-dihydro-2H-pyridin-4-yl]pyrimidin-2-yl]morpholin-2-yl]methyl]-6-oxopyridazin-3-yl]benzonitrile
• 化学式: C₂₇H₂₉N₇O₃
• 分子量: 499.572
• InChiKey: ZLYKGBVZHXGOPL-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (S)-吗啉-2-甲醇 在 盐酸 、 4-二甲氨基吡啶 、 palladium bis[bis(diphenylphosphino)ferrocene] dichloride 、 potassium carbonate 、 caesium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 (S)-3-(1-((4-(5-(1-(2-hydroxyethyl)-1,2,3,6-tetrahydropyridin-4-yl)pyrimidin-2-yl)morpholin-2-yl)methyl)-6-oxo-1,6-dihydropyridazin-3-yl)benzonitrile
  参考文献：
  名称：

  Discovery of substituted 6-pheny-3H-pyridazin-3-one derivatives as novel c-Met kinase inhibitors

  摘要：

  We report a series of phenyl substituted pyridazin-3-ones substituted with morpholino-pyrimidines. The SAR of the phenyl was explored and their c-Met kinase and cell-based inhibitory activity toward c-Met driven cell lines were evaluated. Described herein is a potent c-Met inhibitor by structural modification of the parent morpholino-pyridazinone scaffold, with particular focus on the phenyl and pyrimidine substituents. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.08.067

文献信息

• 신규한 히드라진온이 치환된 피리미딘 유도체 및 그의 용도
  申请人：KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY 한국화학연구원(319980077651)

  公开号：KR101842645B1

  公开（公告）日：2018-03-29

  본 발명은 신규한 히드라진온이 치환된 피리미딘 유도체 또는 이의 약제학적 허용 가능한 염, 이들을 유효성분으로 포함하는 c-Met 티로신 키나아제 활성 억제용 약제학적 조성물 및 이상증식성 질환(hyper proliferative disorder)의 예방 또는 치료용 약제학적 조성물에 관한 것이다. 본 발명은 c-Met 티로신 키나아제의 활성을 효율적으로 억제함으로써 비정상적인 키나제의 활성으로 인한 과도한 세포 증식 및 성장과 관련된 다양한 이상증식성 질환, 예를 들어 암, 건선, 류마티스 관절염, 당뇨병성 망막증 등의 치료제로 유용하게 이용될 수 있다.

  本发明涉及一种新型的已替代的嘧啶衍生物或其药学上可接受的盐，包括这些作为有效成分的用于抑制c-Met酪氨酸激酶活性的药学组合物，以及用于预防或治疗增生性疾病的药学组合物。本发明通过有效地抑制c-Met酪氨酸激酶的活性，可以将其用作治疗与异常激酶活性相关的过度细胞增殖和生长的各种增生性疾病，例如癌症、银屑病、类风湿性关节炎、糖尿病性视网膜病变等。
• Discovery of substituted 6-pheny-3H-pyridazin-3-one derivatives as novel c-Met kinase inhibitors
  作者：Seung-Tae Kang、Eun-Young Kim、Raghavendra Archary、Heejung Jung、Chi Hoon Park、Chang-Soo Yun、Jong Yeon Hwang、Sang Un Choi、Chonghak Chae、Chong Ock Lee、Hyoung Rae Kim、Jae Du Ha、Dohyun Ryu、Sung Yun Cho

  DOI：10.1016/j.bmcl.2014.08.067

  日期：2014.11

  We report a series of phenyl substituted pyridazin-3-ones substituted with morpholino-pyrimidines. The SAR of the phenyl was explored and their c-Met kinase and cell-based inhibitory activity toward c-Met driven cell lines were evaluated. Described herein is a potent c-Met inhibitor by structural modification of the parent morpholino-pyridazinone scaffold, with particular focus on the phenyl and pyrimidine substituents. (C) 2014 Elsevier Ltd. All rights reserved.