2-(4-chloro-2,6-dimethyl-phenoxy)-4-(S)-(1-hydroxymethyl-propylamino)-6,N-dimethyl-nicotinamide | 351380-46-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(4-chloro-2,6-dimethyl-phenoxy)-4-(S)-(1-hydroxymethyl-propylamino)-6,N-dimethyl-nicotinamide
• 英文别名: 2-(4-chloro-2,6-dimethylphenoxy)-4-{[(2S)-1-hydroxybutan-2-yl]amino}-N,6-dimethylpyridine-3-carboxamide；2-(4-chloro-2,6-dimethylphenoxy)-4-[[(2S)-1-hydroxybutan-2-yl]amino]-N,6-dimethylpyridine-3-carboxamide
• CAS: 351380-46-6
• 化学式: C₂₀H₂₆ClN₃O₃
• 分子量: 391.898
• InChiKey: PBZWSSIFISEGAS-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  83.5
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-chloro-2-(4-chloro-2,6-dimethylphenoxy)-N,6-dimethylpyridine-3-carboxamide 、 (S)-(+)-2-氨基-1-丁醇 以 N-甲基吡咯烷酮 为溶剂， 以25.87 g的产率得到2-(4-chloro-2,6-dimethyl-phenoxy)-4-(S)-(1-hydroxymethyl-propylamino)-6,N-dimethyl-nicotinamide
  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：Chen L. Yuhpyng

  公开号：US20050032846A1

  公开（公告）日：2005-02-10

  A pharmaceutical composition for treatment of a disorder or condition the treatment of which can be effected or facilitated by antagonizing Corticotropin Releasing Factor (CRF). The pharmaceutical composition includes a pharmaceutically acceptable carrier and an effective amount to treat the disorder or condition of the following compound: or a pharmaceutically acceptable salt thereof, wherein A, B, Z, R 3 , R 4 , and R 5 are as defined herein.

  一种用于治疗可以通过拮抗促肾上腺皮质激素释放因子（CRF）来治疗或促进治疗的疾病或病状的药物组合物。该药物组合物包括一种药用载体和以下化合物的有效治疗剂量或其药用可接受盐：或其药用可接受盐，其中A、B、Z、R3、R4和R5如本文所定义。
• 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