N-[2-[8-(2-chlorophenyl)-2-methyl-6-(4-methylpiperazin-1-yl)purin-9-yl]ethyl]acetamide | 1335196-94-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-[2-[8-(2-chlorophenyl)-2-methyl-6-(4-methylpiperazin-1-yl)purin-9-yl]ethyl]acetamide
• CAS: 1335196-94-5
• 化学式: C₂₁H₂₆ClN₇O
• 分子量: 427.937
• InChiKey: JNIAMAWGDBKLIP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  79.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[2-[8-(2-chlorophenyl)-2-methyl-6-(4-methylpiperazin-1-yl)purin-9-yl]ethyl]acetamide 在 盐酸 作用下， 以 乙醚 、 水 、 丙酮 、 乙腈 为溶剂， 反应 1.0h， 生成 N-[2-[8-(2-chlorophenyl)-2-methyl-6-(4-methylpiperazin-1-yl)purin-9-yl]ethyl]acetamide hydrochloride
  参考文献：
  名称：

  Selective Cannabinoid Receptor Type 2 (CB2) Agonists: Optimization of a Series of Purines Leading to the Identification of a Clinical Candidate for the Treatment of Osteoarthritic Pain

  摘要：

  A focused screening strategy identified thienopyrimidine 12 as a cannabinoid receptor type 2 agonist (hCB2) with moderate selectivity over the hCB1 receptor. This initial hit suffered from poor in vitro metabolic stability and high in vivo clearance. Structure-activity relationships describe the optimization and modification to a new more polar series of purine CB2 agonists. Examples from this novel scaffold were found to be highly potent and fully efficacious agonists of the human CB2 receptor with excellent selectivity against CBI, often having no CBI agonist activity at the highest concentration measured (>100 mu M). Compound 26 is a centrally penetrant molecule which possesses good biopharmaceutical properties, is highly water-soluble, and demonstrates robust oral activity in rodent models of joint pain. In addition, the peripherally restricted molecule 22 also demonstrated significant efficacy in the same analgesic model of rodent inflammatory pain.

  DOI：

  10.1021/jm400305d
• 作为产物：
  描述：

  2-甲基-4,6-二氯-5-氨基嘧啶 在 氨 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 水 、 异丙醇 为溶剂， 反应 38.0h， 生成 N-[2-[8-(2-chlorophenyl)-2-methyl-6-(4-methylpiperazin-1-yl)purin-9-yl]ethyl]acetamide
  参考文献：
  名称：

  Selective Cannabinoid Receptor Type 2 (CB2) Agonists: Optimization of a Series of Purines Leading to the Identification of a Clinical Candidate for the Treatment of Osteoarthritic Pain

  摘要：

  A focused screening strategy identified thienopyrimidine 12 as a cannabinoid receptor type 2 agonist (hCB2) with moderate selectivity over the hCB1 receptor. This initial hit suffered from poor in vitro metabolic stability and high in vivo clearance. Structure-activity relationships describe the optimization and modification to a new more polar series of purine CB2 agonists. Examples from this novel scaffold were found to be highly potent and fully efficacious agonists of the human CB2 receptor with excellent selectivity against CBI, often having no CBI agonist activity at the highest concentration measured (>100 mu M). Compound 26 is a centrally penetrant molecule which possesses good biopharmaceutical properties, is highly water-soluble, and demonstrates robust oral activity in rodent models of joint pain. In addition, the peripherally restricted molecule 22 also demonstrated significant efficacy in the same analgesic model of rodent inflammatory pain.

  DOI：

  10.1021/jm400305d

文献信息

• PURINE COMPOUNDS USED AS CB2 AGONISTS
  申请人：Hollinshead Sean Patrick

  公开号：US20120329809A1

  公开（公告）日：2012-12-27

  A compound of the formula (I) and pharmaceutical compositions for the treatment of pain.

  公式（I）的化合物和用于治疗疼痛的药物组合物。
• Selective Cannabinoid Receptor Type 2 (CB2) Agonists: Optimization of a Series of Purines Leading to the Identification of a Clinical Candidate for the Treatment of Osteoarthritic Pain
  作者：Sean P. Hollinshead、Michael W. Tidwell、John Palmer、Rossella Guidetti、Adam Sanderson、Michael P. Johnson、Mark G. Chambers、Jennifer Oskins、Robert Stratford、Peter C. Astles

  DOI：10.1021/jm400305d

  日期：2013.7.25

  A focused screening strategy identified thienopyrimidine 12 as a cannabinoid receptor type 2 agonist (hCB2) with moderate selectivity over the hCB1 receptor. This initial hit suffered from poor in vitro metabolic stability and high in vivo clearance. Structure-activity relationships describe the optimization and modification to a new more polar series of purine CB2 agonists. Examples from this novel scaffold were found to be highly potent and fully efficacious agonists of the human CB2 receptor with excellent selectivity against CBI, often having no CBI agonist activity at the highest concentration measured (>100 mu M). Compound 26 is a centrally penetrant molecule which possesses good biopharmaceutical properties, is highly water-soluble, and demonstrates robust oral activity in rodent models of joint pain. In addition, the peripherally restricted molecule 22 also demonstrated significant efficacy in the same analgesic model of rodent inflammatory pain.