4-chloro-1-(1-methoxymethylpropyl)-6-methyl-1H-[1,2,3]triazolo[4,5-c]pyridine | 221024-28-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并吡啶类
• 英文名称: 4-chloro-1-(1-methoxymethylpropyl)-6-methyl-1H-[1,2,3]triazolo[4,5-c]pyridine
• 英文别名: (R,S)-4-chloro-1-(1-methoxymethylpropyl)-6-methyl-1H-1,2,3-triazolo[4,5-c]pyridine；4-Chloro-1-(1-methoxybutan-2-yl)-6-methyltriazolo[4,5-c]pyridine
• CAS: 221024-28-8
• 化学式: C₁₁H₁₅ClN₄O
• 分子量: 254.719
• InChiKey: PFRHCLYHUKGRDC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  52.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-chloro-1-(1-methoxymethylpropyl)-6-methyl-1H-[1,2,3]triazolo[4,5-c]pyridine 、 2-甲基-4-甲氧基苯胺 在 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 以51%的产率得到SN003
  参考文献：
  名称：

  Synthesis and in vivo evaluation of [11C]SN003 as a PET ligand for CRF1 receptors

  摘要：

  Synthesis and evaluation of [O-methyl-C-11](4-methoxy-2-methylphenyl)[1-(1-methoxymethylpropyl)-6-methyl-1H-[1,2,3]triazolo[4,5-c]pyridin-4-yl]amine or [C-11]SN003 ([C-11]6), as a PET imaging agent for CRF1 receptors, in baboons is described. 4-[1-(1-Methoxymethylpropyl)-6-methyl-H-1-[1,2,3]triazolo[4,5-elpyridin-4-ylamino]-3-methylphenol (5), the precursor molecule for the radiolabeling, was synthesized from 2,4-dichloro-6-methyl-3-nitropyridine in seven steps with 20% overall yield. The total time required for the synthesis of [C-11]SN003 is 30 min from EOB using [C-11]methyl triflate in the presence of NaOH in acetone. The yield of the synthesis is 22% (EOS) with > 99% chemical and radiochemical purities and a specific activity of > 2000 Ci/mmol. PET studies in baboon show that [C-11]6 penetrates the BBB and accumulates in brain. No detectable specific binding was observed, likely due to the rapid metabolism or low density of CRF1 receptors in primate brain. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.02.019
• 作为产物：
  描述：

  2,4-二氯-6-甲基-3-硝基吡啶 在 溶剂黄146 、 N,N-二异丙基乙胺 、 tin(ll) chloride 、 sodium nitrite 作用下， 以 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 3.0h， 生成 4-chloro-1-(1-methoxymethylpropyl)-6-methyl-1H-[1,2,3]triazolo[4,5-c]pyridine
  参考文献：
  名称：

  Synthesis and in vivo evaluation of [11C]SN003 as a PET ligand for CRF1 receptors

  摘要：

  Synthesis and evaluation of [O-methyl-C-11](4-methoxy-2-methylphenyl)[1-(1-methoxymethylpropyl)-6-methyl-1H-[1,2,3]triazolo[4,5-c]pyridin-4-yl]amine or [C-11]SN003 ([C-11]6), as a PET imaging agent for CRF1 receptors, in baboons is described. 4-[1-(1-Methoxymethylpropyl)-6-methyl-H-1-[1,2,3]triazolo[4,5-elpyridin-4-ylamino]-3-methylphenol (5), the precursor molecule for the radiolabeling, was synthesized from 2,4-dichloro-6-methyl-3-nitropyridine in seven steps with 20% overall yield. The total time required for the synthesis of [C-11]SN003 is 30 min from EOB using [C-11]methyl triflate in the presence of NaOH in acetone. The yield of the synthesis is 22% (EOS) with > 99% chemical and radiochemical purities and a specific activity of > 2000 Ci/mmol. PET studies in baboon show that [C-11]6 penetrates the BBB and accumulates in brain. No detectable specific binding was observed, likely due to the rapid metabolism or low density of CRF1 receptors in primate brain. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.02.019

文献信息

• Heterocyclyl-substituted ring-fused pyridines and pyrimidines as corticotropin releasing hormone(CRH) antagonists, useful for treating CNS and stress-related disorders
  申请人：DuPont Pharmaceuticals Company

  公开号：US06245769B1

  公开（公告）日：2001-06-12

  Corticotropin releasing factor (CRF) antagonists of Formula (I): and their use in treating psychiatric disorders and neurological diseases, anxiety-related disorders, post-traumatic stress disorder, supranuclear palsy and feeding disorders as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress in mammals.

  皮质释放因子（CRF）拮抗剂的化学式（I）：及其在治疗精神障碍和神经系统疾病、焦虑相关障碍、创伤后应激障碍、上核性麻痹和进食障碍以及治疗与哺乳动物中的心理病理紊乱和应激相关的结肠过敏性所关联的免疫、心血管或心脏疾病方面的用途。
• US6525056B2
  申请人：——

  公开号：US6525056B2

  公开（公告）日：2003-02-25
• Synthesis and in vivo evaluation of [11C]SN003 as a PET ligand for CRF1 receptors
  作者：J.S. Dileep Kumar、Vattoly J. Majo、Gregory M. Sullivan、Jaya Prabhakaran、Norman R. Simpson、Ronald L. Van Heertum、J. John Mann、Ramin V. Parsey

  DOI：10.1016/j.bmc.2006.02.019

  日期：2006.6

  Synthesis and evaluation of [O-methyl-C-11](4-methoxy-2-methylphenyl)[1-(1-methoxymethylpropyl)-6-methyl-1H-[1,2,3]triazolo[4,5-c]pyridin-4-yl]amine or [C-11]SN003 ([C-11]6), as a PET imaging agent for CRF1 receptors, in baboons is described. 4-[1-(1-Methoxymethylpropyl)-6-methyl-H-1-[1,2,3]triazolo[4,5-elpyridin-4-ylamino]-3-methylphenol (5), the precursor molecule for the radiolabeling, was synthesized from 2,4-dichloro-6-methyl-3-nitropyridine in seven steps with 20% overall yield. The total time required for the synthesis of [C-11]SN003 is 30 min from EOB using [C-11]methyl triflate in the presence of NaOH in acetone. The yield of the synthesis is 22% (EOS) with > 99% chemical and radiochemical purities and a specific activity of > 2000 Ci/mmol. PET studies in baboon show that [C-11]6 penetrates the BBB and accumulates in brain. No detectable specific binding was observed, likely due to the rapid metabolism or low density of CRF1 receptors in primate brain. (c) 2006 Elsevier Ltd. All rights reserved.