2-methylamino-5-bromo-3-iodopyridine | 1476713-49-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-methylamino-5-bromo-3-iodopyridine
• 英文别名: 5-bromo-3-iodo-N-methylpyridin-2-amine
• CAS: 1476713-49-1
• 化学式: C₆H₆BrIN₂
• 分子量: 312.936
• InChiKey: GUKCCBBAFFKSNF-UHFFFAOYSA-N

物化性质

• 沸点：
  315.1±42.0 °C(Predicted)
• 密度：
  2.229±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  24.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-methylamino-5-bromo-3-iodopyridine 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 palladium diacetate 、 potassium carbonate 、 三乙胺 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 7.0h， 生成 5-(1-methyl-1H-pyrazol-4-yl)-3-((trimethylsilyl)ethynyl)-2-methylaminopyridine
  参考文献：
  名称：

  一类含杂芳环炔基化合物及其制备方法和用途

  摘要：

  本发明涉及一类含杂芳环炔基化合物及其制备方法和用途，所述含杂芳环炔基化合物为式(I)的化合物，或其氘代化合物、药学上可接受的盐、溶剂化物、酯、酸、代谢物或前药。本发明所述的式(I)化合物具有对原发性KIT突变和耐药型KIT突变携带的肿瘤细胞具有强效的杀伤效果。#imgabs0#

  公开号：

  CN116730978A
• 作为产物：
  描述：

  5-溴-2-(甲基氨基)吡啶 在 碘 作用下， 以 二甲基亚砜 为溶剂， 以32 %的产率得到2-methylamino-5-bromo-3-iodopyridine
  参考文献：
  名称：

  WO2023/225601

  摘要：

  公开号：

文献信息

• Structure–Activity-Relationship Studies around the 2-Amino Group and Pyridine Core of Antimalarial 3,5-Diarylaminopyridines Lead to a Novel Series of Pyrazine Analogues with Oral in Vivo Activity
  作者：Yassir Younis、Frederic Douelle、Diego González Cabrera、Claire Le Manach、Aloysius T. Nchinda、Tanya Paquet、Leslie J. Street、Karen L. White、K. Mohammed Zabiulla、Jayan T. Joseph、Sridevi Bashyam、David Waterson、Michael J. Witty、Sergio Wittlin、Susan A. Charman、Kelly Chibale

  DOI：10.1021/jm401278d

  日期：2013.11.14

  Replacement of the pyridine core of antimalarial 3,5-diaryl-2-aminopyridines led to the identification of a novel series of pyrazine analogues with potent oral antimalarial activity. However, other changes to the pyridine core and replacement or substitution of the 2-amino group led to loss of antimalarial activity. The 3,5-diaryl-2-arninopyrazine series showed impressive in vitro antiplasmodial activity against the K1 (multidrug resistant) and NF54 (sensitive) strains of Plasmodium falciparum in the nanomolar IC50 range of 6-94 nM while also demonstrating good in vitro metabolic stability in human liver microsomes. In the Plasmodium berghei mouse model, this series generally exhibited good efficacy at low oral doses. One of the frontrunner compounds, 4, displayed potent in vitro antiplasmodial activity with IC50 values of 8.4 and 10 nM against the K1 and NF54 strains, respectively. When evaluated in P. berghei-infected mice, compound 4 was completely curative at an oral dose of 4 x 10 mg/kg.
• Structure–Activity Relationship of 3,5-Diaryl-2-aminopyridine ALK2 Inhibitors Reveals Unaltered Binding Affinity for Fibrodysplasia Ossificans Progressiva Causing Mutants
  作者：Agustin H. Mohedas、You Wang、Caroline E. Sanvitale、Peter Canning、Sungwoon Choi、Xuechao Xing、Alex N. Bullock、Gregory D. Cuny、Paul B. Yu

  DOI：10.1021/jm501177w

  日期：2014.10.9

  There are currently no effective therapies for fibrodysplasia ossificans progressiva (FOP), a debilitating and progressive heterotopic ossification disease caused by activating mutations of ACVR1 encoding the BMP type I receptor kinase ALK2. Recently, a subset of these same mutations of ACVR1 have been identified in-diffuse intrinsic pontine ghoma (DIPG) tumors. Here we describe the structure-activity relationship for a series of novel ALK2 inhibitors based on the 2-aminopyridine compound K02288. Several modifications increased potency in kinase, thermal shift, or cell-based assays of BMP signaling and transcription, as well as selectivity for ALK2 versus closely related BMP AND TGF-beta type I receptor kinases. Compounds in this series exhibited a wide range of in vitro cytotoxicity that was not correlated with potency or selectivity, suggesting mechanisms independent of BMP or TGF-beta inhibiton. This study also highlights a potent 2-methylpyridine derivative 10 (LDN 214117) with a high degree of selectivity for ALK2 and low cytotoxicity that could provide a template for preclinical development. contrary to the notion that activating mutations of ALK2 might alter inhibitor efficacy due to potential conformational changes in the ATP-binding site, the compounds demonstrated consistent binding to a panel of mutant and wild-type ALK2 proteins. Thus, BMP inhibitors identified via activity against wild-type ALK2 signaling are likely to be of clinical relevance for the diverse ALK2 mutant proteins associated with FOP and DIPG.