4-iodo-6-methyl-pyrimidine | 1378865-35-0

• 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: 4-iodo-6-methyl-pyrimidine
• 英文别名: 4-Jod-6-methyl-pyrimidin；4-Iodo-6-methylpyrimidine
• CAS: 1378865-35-0
• 化学式: C₅H₅IN₂
• mdl: MFCD17168868
• 分子量: 220.013
• InChiKey: GHNXXBPTGLYEML-UHFFFAOYSA-N

物化性质

• 沸点：
  249.0±20.0 °C(Predicted)
• 密度：
  1.926±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-iodo-6-methyl-pyrimidine 在 乙醇 、 氨 、 氢溴酸 、 溴 作用下， 生成 4-氨基-5-溴-6-甲基嘧啶
  参考文献：
  名称：

  Gabriel; Colman, Chemische Berichte, 1901, vol. 34, p. 1242

  摘要：

  DOI：
• 作为产物：
  描述：

  2,4-二氯-6-甲基嘧啶 在 氢碘酸 作用下， 生成 4-iodo-6-methyl-pyrimidine
  参考文献：
  名称：

  Gabriel; Colman, Chemische Berichte, 1899, vol. 32, p. 1534,2934

  摘要：

  DOI：

文献信息

• Gabriel; Colman, Chemische Berichte, 1899, vol. 32, p. 1533,2930, 2934
  作者：Gabriel、Colman

  DOI：——

  日期：——
• 1,3,8-Triazaspiro[4.5]decane-2,4-diones as Efficacious Pan-Inhibitors of Hypoxia-Inducible Factor Prolyl Hydroxylase 1–3 (HIF PHD1–3) for the Treatment of Anemia
  作者：Petr Vachal、Shouwu Miao、Joan M. Pierce、Deodial Guiadeen、Vincent J. Colandrea、Matthew J. Wyvratt、Scott P. Salowe、Lisa M. Sonatore、James A. Milligan、Richard Hajdu、Anantha Gollapudi、Carol A. Keohane、Russell B. Lingham、Suzanne M. Mandala、Julie A. DeMartino、Xinchun Tong、Michael Wolff、Dietrich Steinhuebel、Gerard R. Kieczykowski、Fred J. Fleitz、Kevin Chapman、John Athanasopoulos、Gregory Adam、Can D. Akyuz、Dhirendra K. Jena、Jeffrey W. Lusen、Juncai Meng、Benjamin D. Stein、Lei Xia、Edward C. Sherer、Jeffrey J. Hale

  DOI：10.1021/jm201542d

  日期：2012.4.12

  The discovery of 1,3,8-triazaspiro[4.5]decane-2,4-diones (spirohydantoins) as a structural class of pan-inhibitors of the prolyl hydroxylase (PHD) family of enzymes for the treatment of anemia is described. The initial hit class, spirooxindoles, was identified through affinity selection mass spectrometry (AS-MS) and optimized for PHD2 inhibition and optimal PK/PD profile (short-acting PHDi inhibitors). 1,3,8-Triazaspiro[4.5]decane-2,4-diones (spirohydantoins) were optimized as an advanced lead class derived from the original spiroindole hit. A new set of general conditions for C-N coupling, developed using a high-throughput experimentation (HTE) technique, enabled a full SAR analysis of the spirohydantoins. This rapid and directed SAR exploration has resulted in the first reported examples of hydantoin derivatives with good PK in preclinical species. Potassium channel off-target activity (hERG) was successfully eliminated through the systematic introduction of acidic functionality to the molecular structure. Undesired upregulation of alanine aminotransferese (ALT) liver enzymes was mitigated and a robust on-/off-target margin was achieved. Spirohydantoins represent a class of highly efficacious, short-acting PHD1-3 inhibitors causing a robust erythropoietin (EPO) upregulation in vivo in multiple preclinical species. This profile deems spirohydantoins as attractive short-acting PHDi inhibitors with the potential for treatment of anemia.