5-chloropyrazine-2-boronic acid | 1309982-45-3

• 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: 5-chloropyrazine-2-boronic acid
• 英文别名: (5-Chloropyrazin-2-YL)boronic acid
• CAS: 1309982-45-3
• 化学式: C₄H₄BClN₂O₂
• mdl: MFCD09607635
• 分子量: 158.352
• InChiKey: ZJAIXYVFBKIGPS-UHFFFAOYSA-N

物化性质

• 沸点：
  337.4±52.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-bromo-5-fluoro-7-methoxy-3,3-dimethyl-1-(2-nitrophenyl)indoline 、 5-chloropyrazine-2-boronic acid 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以98%的产率得到
  参考文献：
  名称：

  Discovery of 4-Aryl-7-Hydroxyindoline-Based P2Y₁ Antagonists as Novel Antiplatelet Agents

  摘要：

  Adenosine diphosphate (ADP)-mediated platelet aggregation is signaled through two distinct G protein-coupled receptors (GPCR) on the platelet surface: P2Y(12) and P2Y(1). Blocking P2Y(12) receptor is a clinically well-validated strategy for antithrombotic therapy. P2Y(1) antagonists have been shown to have the potential to provide equivalent antithrombotic efficacy as P2Y(12) inhibitors with reduced bleeding in preclinical animal models. We have previously reported the discovery of a potent and orally bioavailable P2Y(1) antagonist, I. This paper describes further optimization of 1 by introducing 4-aryl groups at the hydroxylindoline in two series. In the neutral series, 10q was identified with excellent potency and desirable pharmacokinetic (PK) profile. It also demonstrated similar antithrombotic efficacy with less bleeding compared with the known P2Y(12) antagonist prasugrel in rabbit efficacy/bleeding models. In the basic series, 20c (BMS-884775) was discovered with an improved PK and liability profile over 1. These results support P2Y(1) antagonism as a promising new antiplatelet target.

  DOI：

  10.1021/jm5006226

文献信息

• Synthesis and SAR of a series of mGlu7 NAMs based on an ethyl-8-methoxy-4-(4-phenylpiperazin-1-yl)quinoline carboxylate core
  作者：Jacob J. Kalbfleisch、Carson W. Reed、Charlotte Park、Paul K. Spearing、Marc C. Quitalig、Matthew T. Jenkins、Alice L. Rodriguez、Anna L. Blobaum、P. Jeffrey Conn、Colleen M. Niswender、Craig W. Lindsley

  DOI：10.1016/j.bmcl.2020.127529

  日期：2020.11

  A High-Throughput Screening (HTS) campaign identified a fundamentally new mGlu₇ NAM chemotype, based on an ethyl-8-methoxy-4-(4-phenylpiperazin-1-yl)quinolone carboxylate core. The initial hit, VU0226390, was a potent mGlu₇ NAM (IC₅₀ = 647 nM, 6% L-AP4 min) with selectivity versus the other group III mGlu receptors (>30 μM vs. mGlu₄ and mGlu₈). A multi-dimensional optimization effort surveyed all regions of this new chemotype, and found very steep SAR, reminiscent of allosteric modulators, and unexpected piperazine mimetics (whereas classical bioisosteres failed). While mGlu₇ NAM potency could be improved (IC₅₀s ~ 350 nM), the necessity of the ethyl ester moiety and poor physiochemical and DMPK properties precluded optimization towards in vivo tool compounds or clinical candidates. Still, this hit-to-lead campaign afforded key medicinal chemistry insights and new opportunities.
• Discovery of 4-Aryl-7-Hydroxyindoline-Based P2Y₁ Antagonists as Novel Antiplatelet Agents
  作者：Wu Yang、Yufeng Wang、Amy Lai、Jennifer X. Qiao、Tammy C. Wang、Ji Hua、Laura A. Price、Hong Shen、Xue-qing Chen、Pancras Wong、Earl Crain、Carol Watson、Christine S. Huang、Dietmar A. Seiffert、Robert Rehfuss、Ruth R. Wexler、Patrick Y. S. Lam

  DOI：10.1021/jm5006226

  日期：2014.7.24

  Adenosine diphosphate (ADP)-mediated platelet aggregation is signaled through two distinct G protein-coupled receptors (GPCR) on the platelet surface: P2Y(12) and P2Y(1). Blocking P2Y(12) receptor is a clinically well-validated strategy for antithrombotic therapy. P2Y(1) antagonists have been shown to have the potential to provide equivalent antithrombotic efficacy as P2Y(12) inhibitors with reduced bleeding in preclinical animal models. We have previously reported the discovery of a potent and orally bioavailable P2Y(1) antagonist, I. This paper describes further optimization of 1 by introducing 4-aryl groups at the hydroxylindoline in two series. In the neutral series, 10q was identified with excellent potency and desirable pharmacokinetic (PK) profile. It also demonstrated similar antithrombotic efficacy with less bleeding compared with the known P2Y(12) antagonist prasugrel in rabbit efficacy/bleeding models. In the basic series, 20c (BMS-884775) was discovered with an improved PK and liability profile over 1. These results support P2Y(1) antagonism as a promising new antiplatelet target.