12-Cyclopentyl-10-ethyl-5-phenyl-3,4,6,11,12-pentazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,10-tetraene

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 12-Cyclopentyl-10-ethyl-5-phenyl-3,4,6,11,12-pentazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,10-tetraene
• 化学式: C₂₀H₂₃N₅
• 分子量: 333.436
• InChiKey: WHTVLUBBPXQFPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  48.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  7H-吡唑并[3,4-c]吡啶-7-硫酮,1-环戊基-3-乙基-1,4,5,6-四氢- 在 吡啶 、 silica gel 作用下， 以 乙醚 为溶剂， 反应 9.0h， 生成 12-Cyclopentyl-10-ethyl-5-phenyl-3,4,6,11,12-pentazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,10-tetraene
  参考文献：
  名称：

  SAR of a Series of 5,6-Dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridines as Potent Inhibitors of Human Eosinophil Phosphodiesterase

  摘要：

  The potency and physical properties of a previously reported 7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine series of human eosinophil phosphodiesterase inhibitors were improved by tying the lactam moiety into a triazolo ring. The resulting 5,6-dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-alpha]pyridine series provided nonionizable analogs with melting point properties suitable for micronization. Substitution at the 3-position of the 5,6-dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-alpha]pyridine tricycle led to a 2-thienyl analog, 19 (tofimilast), a potent PDE4 inhibitor with low oral bioavailability and no emesis-associated behaviors in ferrets at plasma concentrations up to 152 ng/mL.

  DOI：

  10.1021/jm060904g

文献信息

• Pde4 inhibitor and an anti-cholinergic agent in combination for treating obstructive airways diseases
  申请人：——

  公开号：US20040147544A1

  公开（公告）日：2004-07-29

  The present invention relates to a combination of a selective PDB4 inhibitor and an anticholinergic agent for simultaneous, sequential or separate administration by the inhaled route in the treatment of an obstructive airways or other inflammatory disease, with the proviso that the anticholinergic agent is not a tiotropium salt.

  本发明涉及一种选择性 PDB4 抑制剂和抗胆碱能药物的组合，用于通过吸入途径同时、连续或单独给药，治疗阻塞性气道疾病或其他炎症性疾病，但抗胆碱能药物不是噻托溴铵盐。
• [EN] NEW COMBINATION<br/>[FR] NOUVELLE COMBINAISON
  申请人：ALTANA PHARMA AG

  公开号：WO2003024488A2

  公开（公告）日：2003-03-27

  The invention relates to the combined administration of PDE4 or PDE3/4 inhibitors and leukotriene receptor antagonists for the treatment of respiratory tract disorders.
• SAR of a Series of 5,6-Dihydro-(9<i>H</i>)-pyrazolo[3,4-<i>c</i>]-1,2,4-triazolo[4,3-α]pyridines as Potent Inhibitors of Human Eosinophil Phosphodiesterase
  作者：Allen J. Duplantier、Elizabeth L. Bachert、John B. Cheng、Victoria L. Cohan、Teresa H. Jenkinson、Kenneth G. Kraus、Michael W. McKechney、Joann D. Pillar、John W. Watson

  DOI：10.1021/jm060904g

  日期：2007.1.1

  The potency and physical properties of a previously reported 7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine series of human eosinophil phosphodiesterase inhibitors were improved by tying the lactam moiety into a triazolo ring. The resulting 5,6-dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-alpha]pyridine series provided nonionizable analogs with melting point properties suitable for micronization. Substitution at the 3-position of the 5,6-dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-alpha]pyridine tricycle led to a 2-thienyl analog, 19 (tofimilast), a potent PDE4 inhibitor with low oral bioavailability and no emesis-associated behaviors in ferrets at plasma concentrations up to 152 ng/mL.