N-{4-[3-(5-methylpyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}acetamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: N-{4-[3-(5-methylpyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}acetamide
• 英文别名: N-[4-[3-(5-methylpyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]acetamide
• 化学式: C₂₀H₁₇N₅O
• 分子量: 343.388
• InChiKey: LIKDYDWODKJNQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基-4-溴吡啶 在 4-二甲氨基吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 四(三苯基膦)钯 、 四丁基氟化铵 、 caesium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 9.0h， 生成 N-{4-[3-(5-methylpyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}acetamide
  参考文献：
  名称：

  Discovery of 4-Azaindole Inhibitors of TGFβRI as Immuno-oncology Agents

  摘要：

  The multifunctional cytokine TGF beta plays a central role in regulating antitumor immunity. It has been postulated that inhibition of TGF beta signaling in concert with checkpoint blockade will provide improved and durable immune response against tumors. Herein, we describe a novel series of 4-azaindole TGF beta receptor kinase inhibitors with excellent selectivity for TGF beta receptor 1 kinase. The combination of compound 3f and an antimouse-PD-1 antibody demonstrated significantly improved antitumor efficacy compared to either treatment alone in a murine tumor model.

  DOI：

  10.1021/acsmedchemlett.8b00357

文献信息

• TGF BETA R ANTAGONISTS
  申请人：Bristol-Myers Squibb Company

  公开号：US20160176871A1

  公开（公告）日：2016-06-23

  The invention relates generally to compounds that modulate the activity of TGFβR-1 and TGFβR-2, pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.

  这项发明通常涉及调节TGFβR-1和TGFβR-2活性的化合物，包含这些化合物的药物组合物以及利用该发明的化合物治疗增殖性疾病和失调凋亡疾病（如癌症）的方法。
• US9708316B2
  申请人：——

  公开号：US9708316B2

  公开（公告）日：2017-07-18
• [EN] TGFβ RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DES RÉCEPTEURS TGFΒ
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2016106266A1

  公开（公告）日：2016-06-30

  The invention relates generally to compounds of formula (I) that modulate the activity of TGFβR-1 and TGFβR-2, pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.
• Discovery of 4-Azaindole Inhibitors of TGFβRI as Immuno-oncology Agents
  作者：Yong Zhang、Yufen Zhao、Andrew J. Tebben、Steven Sheriff、Max Ruzanov、Mark P. Fereshteh、Yi Fan、Jonathan Lippy、Jesse Swanson、Ching-Ping Ho、Barri S. Wautlet、Anne Rose、Karen Parrish、Zheng Yang、Andrew F. Donnell、Liping Zhang、Brian E. Fink、Gregory D. Vite、Karen Augustine-Rauch、Joseph Fargnoli、Robert M. Borzilleri

  DOI：10.1021/acsmedchemlett.8b00357

  日期：2018.11.8

  The multifunctional cytokine TGF beta plays a central role in regulating antitumor immunity. It has been postulated that inhibition of TGF beta signaling in concert with checkpoint blockade will provide improved and durable immune response against tumors. Herein, we describe a novel series of 4-azaindole TGF beta receptor kinase inhibitors with excellent selectivity for TGF beta receptor 1 kinase. The combination of compound 3f and an antimouse-PD-1 antibody demonstrated significantly improved antitumor efficacy compared to either treatment alone in a murine tumor model.