7-((2R,5R)-2-methyl-5-phenylmorpholino)-1H-pyrido[2,3-b]-[1,4]oxazin-2(3H)-one | 1349831-01-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 7-((2R,5R)-2-methyl-5-phenylmorpholino)-1H-pyrido[2,3-b]-[1,4]oxazin-2(3H)-one
• 英文别名: 7-((2R,5R)-2-methyl-5-phenylmorpholino)-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one；7-[(2R,5R)-2-methyl-5-phenylmorpholin-4-yl]-1H-pyrido[2,3-b][1,4]oxazin-2-one
• CAS: 1349831-01-1
• 化学式: C₁₈H₁₉N₃O₃
• 分子量: 325.367
• InChiKey: YEFMFDYTYWBJCT-WBMJQRKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  63.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (2R,5R)-2-methyl-5-phenylmorpholin-3-one 在 tris-(dibenzylideneacetone)dipalladium(0) 、 5-(diisopropylphosphino)-1',3',5'-triphenyl-1'H-1,4'-bipyrazole 、 红铝 、 lithium tert-butoxide 作用下， 以 六甲基磷酰三胺 、 2-甲基-2-丁醇 、 甲苯 为溶剂， 生成 7-((2R,5R)-2-methyl-5-phenylmorpholino)-1H-pyrido[2,3-b]-[1,4]oxazin-2(3H)-one
  参考文献：
  名称：

  Identification of Morpholino-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-ones as Nonsteroidal Mineralocorticoid Antagonists

  摘要：

  A novel series of morpholine-based non steroidal mineralocorticoid receptor antagonists is reported. Starting from a pyrrolidine HTS hit 9 that possessed modest potency but excellect selectivity versus related nuclear hormone receptors, a series of libraries led to identification of morpholine lead 10. After further optimization, cis disubstituted morpholine 22 was discovered, which showed a 45-fold boost in binding affinity and corresponding functional potency compared to 13. While 22 had high clearance in rat, it provided sufficient exposure at high doses to favorably assess in vivo efficacy (increased urinary Na+/K+ ratio) and safety. In contrast to rat, the dog and human MetID and PK profiles of 22 were adequate, suggesting that it could be suitable as a potential clinical asset.

  DOI：

  10.1021/acs.jmedchem.7b01515

文献信息

• MORPHOLINE COMPOUNDS
  申请人：Casimiro-Garcia Agustin

  公开号：US20110281854A1

  公开（公告）日：2011-11-17

  Mineralocorticoid receptor antagonists (MRa), pharmaceutical compositions containing such inhibitors and the use of such inhibitors to treat, for example, diabetic nephropathy and hypertension in mammals, including humans.

  矿物皮质激素受体拮抗剂（MRa），含有这类抑制剂的药物组合物以及利用这类抑制剂治疗哺乳动物，包括人类，例如糖尿病肾病和高血压。