4-氨基-3-溴哒嗪 | 55928-84-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 4-氨基-3-溴哒嗪
• 英文名称: 4-Amino-3-brompyridazin
• 英文别名: 3-bromo-pyridazin-4-ylamine；4-amino-3-bromopyridazine；3-Bromopyridazin-4-amine
• CAS: 55928-84-2
• 化学式: C₄H₄BrN₃
• 分子量: 174.0
• InChiKey: QYOMPWRHTAMYFX-UHFFFAOYSA-N

物化性质

• 沸点：
  354.9±22.0 °C(Predicted)
• 密度：
  1.844±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  51.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(5-fluoro-2-methylphenyl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol 、 4-氨基-3-溴哒嗪 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 1-(4-aminopyridazin-3-yl)-6-(5-fluoro-2-methylphenyl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol
  参考文献：
  名称：

  Identification of Highly Efficacious Glucocorticoid Receptor Agonists with a Potential for Reduced Clinical Bone Side Effects

  摘要：

  Synthesis and structure-activity relationship (SAR) of a series of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain "diazaindole" moieties and display different transcriptional regulatory profiles in vitro and are considered "dissociated" between gene transrepression and transactivation. The lead optimization effort described in this article focused in particular on limiting the transactivation of genes which result in bone side effects and these were assessed in vitro in MG-63 osteosarcoma cells, leading to the identification of (R)-18 and (R)-21. These compounds maintained anti-inflammatory activity in vivo in collagen induced arthritis studies in mouse but had reduced effects on bone relevant parameters compared to the widely used synthetic glucocorticoid prednisolone 2 in vivo. To our knowledge, we are the first to report on selective glucocorticoid ligands with reduced bone loss in a preclinical in vivo model.

  DOI：

  10.1021/jm4019178
• 作为产物：
  描述：

  4-氨基哒嗪 在 溴 、 溶剂黄146 作用下， 以11 %的产率得到4-氨基-3-溴哒嗪
  参考文献：
  名称：

  WO2023/60057

  摘要：

  公开号：

文献信息

• Glucocorticoid mimetics, methods of making them, pharmaceutical compositions and uses thereof
  申请人：Bekkali Younes

  公开号：US20050176706A1

  公开（公告）日：2005-08-11

  Compounds of Formula (IA), (IB), (IC), and (ID) wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are as respectively defined herein for Formula (IA), (IB), (IC), and (ID), or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

  化合物的公式为（IA），（IB），（IC）和（ID），其中R1，R2，R3，R4，R5和R6分别定义为公式（IA），（IB），（IC）和（ID）中所述，或其互变异构体，前药，溶剂化物或盐; 包含这些化合物的药物组合物以及使用这些化合物调节糖皮质激素受体功能的方法和治疗由糖皮质激素受体功能介导或以炎症，过敏或增生过程为特征的疾病状态或病情的方法。
• Biarylsulfonamide CCR9 inhibitors for inflammatory bowel disease
  作者：Jing Zhang、Jan Romero、Audrey Chan、Jennifer Goss、Sabrina Stucka、Jason Cross、Brian Chamberlain、Mustafa Varoglu、Haoqun Chandonnet、Dominic Ryan、Blaise Lippa

  DOI：10.1016/j.bmcl.2015.06.046

  日期：2015.9

  Inflammatory bowel disease, including Crohn's disease and ulcerative colitis, affects millions of people worldwide. CCR9 has been shown to be a key chemokine receptor mediating the local inflammatory responses in the GI tract. The CCR9 inhibitor Vercirnon advanced to phase 3 clinical trials, but carries several liabilities which we sought to improve. (C) 2015 Elsevier Ltd. All rights reserved.
• WO2023/60057
  申请人：——

  公开号：——

  公开（公告）日：——
• Identification of Highly Efficacious Glucocorticoid Receptor Agonists with a Potential for Reduced Clinical Bone Side Effects
  作者：Christian Harcken、Doris Riether、Daniel Kuzmich、Pingrong Liu、Raj Betageri、Mark Ralph、Michel Emmanuel、Jonathan T. Reeves、Angela Berry、Donald Souza、Richard M. Nelson、Alison Kukulka、Tazmeen N. Fadra、Ljiljana Zuvela-Jelaska、Roger Dinallo、Jörg Bentzien、Gerald H. Nabozny、David S. Thomson

  DOI：10.1021/jm4019178

  日期：2014.2.27

  Synthesis and structure-activity relationship (SAR) of a series of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain "diazaindole" moieties and display different transcriptional regulatory profiles in vitro and are considered "dissociated" between gene transrepression and transactivation. The lead optimization effort described in this article focused in particular on limiting the transactivation of genes which result in bone side effects and these were assessed in vitro in MG-63 osteosarcoma cells, leading to the identification of (R)-18 and (R)-21. These compounds maintained anti-inflammatory activity in vivo in collagen induced arthritis studies in mouse but had reduced effects on bone relevant parameters compared to the widely used synthetic glucocorticoid prednisolone 2 in vivo. To our knowledge, we are the first to report on selective glucocorticoid ligands with reduced bone loss in a preclinical in vivo model.