4-chloro-6-methyl-2-(4-chloro-2,6-dimethylphenoxy)-1-nicotinic acid methyl ester | 351382-80-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-chloro-6-methyl-2-(4-chloro-2,6-dimethylphenoxy)-1-nicotinic acid methyl ester
• 英文别名: methyl 4-chloro-2-(4-chloro-2,6-dimethylphenoxy)-6-methylnicotinate；4-chloro-6-methyl-2-(4-Chloro-2,6-dimethyl-phenoxy)-nicotinic acid methyl ester；2-(4-Chloro-2,6-dimethyl-phenoxy)-4-chloro-6-methyl-nicotinic acid methyl ester；methyl 4-chloro-2-(4-chloro-2,6-dimethylphenoxy)-6-methylpyridine-3-carboxylate
• CAS: 351382-80-4
• 化学式: C₁₆H₁₅Cl₂NO₃
• 分子量: 340.206
• InChiKey: NXRZMIDGPGTPOC-UHFFFAOYSA-N

物化性质

• 熔点：
  130-134 °C
• 沸点：
  406.4±45.0 °C(Predicted)
• 密度：
  1.289±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-chloro-6-methyl-2-(4-chloro-2,6-dimethylphenoxy)-1-nicotinic acid methyl ester 在 lithium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 4-Chloro-2-(4-chloro-2,6-dimethylphenoxy)-6-methylpyridine-3-carboxylic acid
  参考文献：
  名称：

  2-Aryloxy-4-alkylaminopyridines: Discovery of Novel Corticotropin-Releasing Factor 1 Antagonists

  摘要：

  An orally active clinical candidate of corticotropin-releasing factor 1 (CRF(1)) antagonist 1 showed a significant positive food effect in dog and human after oral administration. Efforts to address the food effect issue led us to explore and discover compounds in series 2 as orally active CRF(1) receptor antagonists, in which some compounds showed improved physicochemical properties while retaining desired pharmacological properties. Compound 3a (CP-376395) was selected for further development, due not only to its reduced food effects but also its greater efficacy in CNS models. Compound 3a was advanced to the clinic. The synthesis of representative potential candidates and their in vitro, ex vivo, and in vivo data are described.

  DOI：

  10.1021/jm070579c
• 作为产物：
  描述：

  methyl 4-chloro-2-(4-chloro-2,6-dimethylphenoxy)-6-methylnicotinate N-oxide 在 三氯化磷 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 4-chloro-6-methyl-2-(4-chloro-2,6-dimethylphenoxy)-1-nicotinic acid methyl ester
  参考文献：
  名称：

  2-Aryloxy-4-alkylaminopyridines: Discovery of Novel Corticotropin-Releasing Factor 1 Antagonists

  摘要：

  An orally active clinical candidate of corticotropin-releasing factor 1 (CRF(1)) antagonist 1 showed a significant positive food effect in dog and human after oral administration. Efforts to address the food effect issue led us to explore and discover compounds in series 2 as orally active CRF(1) receptor antagonists, in which some compounds showed improved physicochemical properties while retaining desired pharmacological properties. Compound 3a (CP-376395) was selected for further development, due not only to its reduced food effects but also its greater efficacy in CNS models. Compound 3a was advanced to the clinic. The synthesis of representative potential candidates and their in vitro, ex vivo, and in vivo data are described.

  DOI：

  10.1021/jm070579c

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。
• 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
• US6844351B1
  申请人：——

  公开号：US6844351B1

  公开（公告）日：2005-01-18
• US6956047B1
  申请人：——

  公开号：US6956047B1

  公开（公告）日：2005-10-18