6-chloro-2-methyl-N4-(tetrahydro-2H-pyran-4-yl)-pyrimidine-4,5-diamine | 1231220-81-7

• 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: 6-chloro-2-methyl-N4-(tetrahydro-2H-pyran-4-yl)-pyrimidine-4,5-diamine
• 英文别名: 6-chloro-2-methyl-N4-(tetrahydropyran-4-yl)pyrimidine-4,5-diamine；6-Chloro-2-methyl-N*4*-(tetrahydro-pyran-4-yl)-pyrimidine-4,5-diamine；6-chloro-2-methyl-4-N-(oxan-4-yl)pyrimidine-4,5-diamine
• CAS: 1231220-81-7
• 化学式: C₁₀H₁₅ClN₄O
• 分子量: 242.708
• InChiKey: FAYJZRRSCSYKBJ-UHFFFAOYSA-N

物化性质

• 沸点：
  414.6±45.0 °C(Predicted)
• 密度：
  1.352±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  73.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-chloro-2-methyl-N4-(tetrahydro-2H-pyran-4-yl)-pyrimidine-4,5-diamine 在 盐酸 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 、 乙醇 、 水 、 丙酮 、 乙腈 为溶剂， 反应 35.0h， 生成 8-(2-methoxyphenyl)-2-methyl-6-(4-methylpiperazin-1-yl)-9-tetrahydropyran-4-yl-purine 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 、 4-氨基四氢吡喃盐酸盐 在 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 生成 6-chloro-2-methyl-N4-(tetrahydro-2H-pyran-4-yl)-pyrimidine-4,5-diamine
  参考文献：
  名称：

  Purine Compounds

  摘要：

  该化合物的分子式为，并且用于治疗疼痛的药物组合。

  公开号：

  US20100160288A1

文献信息

• Purine compounds
  申请人：Eli Lilly and Company

  公开号：US08252798B2

  公开（公告）日：2012-08-28

  A compound of the formula: and pharmaceutical compositions for the treatment of pain.

  公式为：的化合物以及用于治疗疼痛的药物组合物。
• The Development of Practical Synthetic Routes to a CB₂ Agonist: Efficient Construction of a Densely Substituted Purine Core
  作者：Amy C. DeBaillie、Chauncey D. Jones、Michael E. Laurila、Nicholas A. Magnus、Michael A. Staszak

  DOI：10.1021/op300278c

  日期：2013.2.15

  An efficient and scalable process for the preparation of a purine-based CB2 agonist was developed. The production route to the requisite purine core relies on N-acylation and sequential substitution of a 5-amino-4,6-dichloropyrimidine with two amine building blocks followed by a cyclocondensation reaction. The chemistry was successfully employed to rapidly prepare over S kg of the active pharmaceutical ingredient. To further improve efficiencies, postproduction development resulted in a rearranged synthesis which reduced the need for pressure reactors and introduced the most costly reagent in the final step.
• PURINE COMPOUNDS
  申请人：Eli Lilly and Company

  公开号：EP2379555B1

  公开（公告）日：2015-02-25
• US8252798B2
  申请人：——

  公开号：US8252798B2

  公开（公告）日：2012-08-28
• [EN] PURINE COMPOUNDS<br/>[FR] COMPOSÉS PURINES
  申请人：LILLY CO ELI

  公开号：WO2010080306A1

  公开（公告）日：2010-07-15

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