2-chloro-6-methyl-3-nitropyridin-4-yl-(1-methoxymethylpropyl)amine | 351382-63-3

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 2-chloro-6-methyl-3-nitropyridin-4-yl-(1-methoxymethylpropyl)amine
• 英文别名: 2-chloro-N-(1-methoxybutan-2-yl)-6-methyl-3-nitropyridin-4-amine
• CAS: 351382-63-3
• 化学式: C₁₁H₁₆ClN₃O₃
• 分子量: 273.719
• InChiKey: AVWYYZLLEJYFQV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  80
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-chloro-6-methyl-3-nitropyridin-4-yl-(1-methoxymethylpropyl)amine 在 溶剂黄146 、 tin(ll) chloride 、 sodium nitrite 作用下， 以 乙醇 、 二氯甲烷 、 水 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
• 作为产物：
  描述：

  4-羟基-6-甲基-3-硝基-2-吡啶醇 在 三乙胺 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 生成 2-chloro-6-methyl-3-nitropyridin-4-yl-(1-methoxymethylpropyl)amine
  参考文献：
  名称：

  三环咪唑并[4,5-b]吡啶-2-酮作为促肾上腺皮质激素释放因子-1拮抗剂的设计与合成。

  摘要：

  本文讨论了三环咪唑并[4,5-b]吡啶-2-酮作为人类促肾上腺皮质激素释放因子受体（CRF（1））拮抗剂的合成和SAR研究。化合物16g被确定为一种功能性拮抗剂，可抑制CRF刺激的环磷酸腺苷生成和CRF诱导的肾上腺皮质营养激素释放。在大鼠体内进行的药代动力学研究表明，16g口服生物可利用的，具有良好的脑部渗透能力，并且半衰期适中。在我们努力确定具有改善的药代动力学特性的CRF（1）拮抗剂的过程中，16g的药物显示出较低的分布体积。

  DOI：

  10.1021/jm050384+

文献信息

• Corticotropin releasing factor antagonists
  申请人：——

  公开号：US20020016328A1

  公开（公告）日：2002-02-07

  Corticotropin-releasing factor (CRF) antagonists having the formulae 1 wherein the dashed lines, A, B, Y, Z, G, R 3 , R 4 , R 5 , R 6 , R 16 and R 17 are as defined in the application, and processes for preparing them. These compounds and their pharmaceutically acceptable salts are useful in the treatment disorders including CNS and stress-related disorders.

  具有以下公式的促肾上腺皮质激素释放因子（CRF）拮抗剂，其中虚线、A、B、Y、Z、G、R3、R4、R5、R6、R16和R17如申请中所定义，并且制备它们的过程。这些化合物及其药用盐可用于治疗包括中枢神经系统和与压力相关的疾病。
• Synthesis, Structure−Activity Relationships, and in Vivo Properties of 3,4-Dihydro-1<i>H</i>-pyrido[2,3-<i>b</i>]pyrazin-2-ones as Corticotropin-Releasing Factor-1 Receptor Antagonists
  作者：Carolyn D. Dzierba、Amy G. Takvorian、Maria Rafalski、Padmaja Kasireddy-Polam、Harvey Wong、Thaddeus F. Molski、Ge Zhang、Yu-Wen Li、Snjezana Lelas、Yong Peng、John F. McElroy、Robert C. Zaczek、Rebecca A. Taub、Andrew P. Combs、Paul J. Gilligan、George L. Trainor

  DOI：10.1021/jm049737f

  日期：2004.11.1

  Corticotropin releasing factor (CRF) is the primary regulator of the hypothalamus-pituitary-adrenal (HPA) axis, coordinating the endocrine, behavioral, and autonomic responses to stress. It has been postulated that small molecules that can antagonize the binding of CRF, to its receptor may serve as a treatment for anxiety-related and/or affective disorders. Members within a series of 3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-ones, exemplified by compound 2 (IC50 = 0.70 nM), were found to be very potent antagonists of CRF1. Compound 8w showed high CRF1 receptor binding affinity and was examined further in vivo. The compound was efficacious in a defensive withdrawal model of anxiety in rats and had a long half-life and reasonable oral bioavailability in dog pharmacokinetic studies.
• CORTICOTROPIN RELEASING FACTOR ANTAGONISTS
  申请人：Pfizer Products Inc.

  公开号：EP1263732A1

  公开（公告）日：2002-12-11
• US6833378B2
  申请人：——

  公开号：US6833378B2

  公开（公告）日：2004-12-21
• US6956047B1
  申请人：——

  公开号：US6956047B1

  公开（公告）日：2005-10-18