2-氯-6-[4-(2-甲基-2-丙基)苯基]吡嗪 | 943997-52-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-氯-6-[4-(2-甲基-2-丙基)苯基]吡嗪
• 英文名称: 2-(4-tert-butylphenyl)-6-chloropyrazine
• 英文别名: 2-(4-(tert-Butyl)phenyl)-6-chloropyrazine
• CAS: 943997-52-2
• 化学式: C₁₄H₁₅ClN₂
• 分子量: 246.739
• InChiKey: BAPSONZYIILSJB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-氯-6-[4-(2-甲基-2-丙基)苯基]吡嗪 、 6-氨基-1,4-苯并二氧杂环 在 tris-(dibenzylideneacetone)dipalladium(0) sodium t-butanolate 、 2-二环己膦基-2'-(N,N-二甲胺)-联苯 作用下， 以 甲苯 为溶剂， 反应 0.33h， 以57%的产率得到6-(4-tert-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)pyrazin-2-amine
  参考文献：
  名称：

  Novel Vanilloid Receptor-1 Antagonists:  1. Conformationally Restricted Analogues of trans-Cinnamides

  摘要：

  The vanilloid receptor-1 (VR1 or TRPV1) is a member of the transient receptor potential (TRP) family of ion channels and plays a role as an integrator of multiple pain-producing stimuli. From a high-throughput screening assay, measuring calcium uptake in TRPV1-expressing cells, we identified an N-aryl trans-cinnamide (AMG9810, compound 9) that acts as a potent TRPV1 antagonist. We have demonstrated the antihyperalgesic properties of 9 in vivo and have also reported the discovery of novel, orally bioavailable cinnamides derived from this lead. Herein, we expand our investigations and describe the synthesis and biological evaluation of a series of conformationally constrained analogues of the s-cis conformer of compound 9. These investigations resulted in the identification of 4-amino- and 4-oxopyrimidine cores as suitable isosteric replacements for the trans-acrylamide moiety. The best examples from this series, pyrimidines 79 and 74, were orally bioavailable and exhibited potent antagonism of both rat (IC50 = 4.5 and 0.6 nM, respectively) and human TRPV1 (IC50 = 7.4 and 3.7 nM, respectively). In addition, compound 74 was shown to be efficacious at blocking a TRPV1-mediated physiological response in vivo in the capsaicin-induced hypothermia model in rats; however, it was ineffective at preventing thermal hyperalgesia induced by complete Freund's adjuvant in rats.

  DOI：

  10.1021/jm070189q
• 作为产物：
  描述：

  2,6-二氯吡嗪 、 4-叔丁基苯硼酸 在 四(三苯基膦)钯 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.33h， 以48%的产率得到2-氯-6-[4-(2-甲基-2-丙基)苯基]吡嗪
  参考文献：
  名称：

  Novel Vanilloid Receptor-1 Antagonists:  1. Conformationally Restricted Analogues of trans-Cinnamides

  摘要：

  The vanilloid receptor-1 (VR1 or TRPV1) is a member of the transient receptor potential (TRP) family of ion channels and plays a role as an integrator of multiple pain-producing stimuli. From a high-throughput screening assay, measuring calcium uptake in TRPV1-expressing cells, we identified an N-aryl trans-cinnamide (AMG9810, compound 9) that acts as a potent TRPV1 antagonist. We have demonstrated the antihyperalgesic properties of 9 in vivo and have also reported the discovery of novel, orally bioavailable cinnamides derived from this lead. Herein, we expand our investigations and describe the synthesis and biological evaluation of a series of conformationally constrained analogues of the s-cis conformer of compound 9. These investigations resulted in the identification of 4-amino- and 4-oxopyrimidine cores as suitable isosteric replacements for the trans-acrylamide moiety. The best examples from this series, pyrimidines 79 and 74, were orally bioavailable and exhibited potent antagonism of both rat (IC50 = 4.5 and 0.6 nM, respectively) and human TRPV1 (IC50 = 7.4 and 3.7 nM, respectively). In addition, compound 74 was shown to be efficacious at blocking a TRPV1-mediated physiological response in vivo in the capsaicin-induced hypothermia model in rats; however, it was ineffective at preventing thermal hyperalgesia induced by complete Freund's adjuvant in rats.

  DOI：

  10.1021/jm070189q

文献信息

• Novel Vanilloid Receptor-1 Antagonists:  1. Conformationally Restricted Analogues of <i>trans</i>-Cinnamides
  作者：Mark H. Norman、Jiawang Zhu、Christopher Fotsch、Yunxin Bo、Ning Chen、Partha Chakrabarti、Elizabeth M. Doherty、Narender R. Gavva、Nobuko Nishimura、Thomas Nixey、Vassil I. Ognyanov、Robert M. Rzasa、Markian Stec、Sekhar Surapaneni、Rami Tamir、Vellarkad N. Viswanadhan、James J. S. Treanor

  DOI：10.1021/jm070189q

  日期：2007.7.1

  The vanilloid receptor-1 (VR1 or TRPV1) is a member of the transient receptor potential (TRP) family of ion channels and plays a role as an integrator of multiple pain-producing stimuli. From a high-throughput screening assay, measuring calcium uptake in TRPV1-expressing cells, we identified an N-aryl trans-cinnamide (AMG9810, compound 9) that acts as a potent TRPV1 antagonist. We have demonstrated the antihyperalgesic properties of 9 in vivo and have also reported the discovery of novel, orally bioavailable cinnamides derived from this lead. Herein, we expand our investigations and describe the synthesis and biological evaluation of a series of conformationally constrained analogues of the s-cis conformer of compound 9. These investigations resulted in the identification of 4-amino- and 4-oxopyrimidine cores as suitable isosteric replacements for the trans-acrylamide moiety. The best examples from this series, pyrimidines 79 and 74, were orally bioavailable and exhibited potent antagonism of both rat (IC50 = 4.5 and 0.6 nM, respectively) and human TRPV1 (IC50 = 7.4 and 3.7 nM, respectively). In addition, compound 74 was shown to be efficacious at blocking a TRPV1-mediated physiological response in vivo in the capsaicin-induced hypothermia model in rats; however, it was ineffective at preventing thermal hyperalgesia induced by complete Freund's adjuvant in rats.