(6aR,9aS)-5-ethyl-5,6a,7,8,9,9a-hexahydro-2-(phenylmethyl)cyclopent[4,5]imidazo[2,1-b]purin-4(1H)-one | 191982-79-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: (6aR,9aS)-5-ethyl-5,6a,7,8,9,9a-hexahydro-2-(phenylmethyl)cyclopent[4,5]imidazo[2,1-b]purin-4(1H)-one
• 英文别名: (11R,15S)-4-benzyl-8-ethyl-1,3,5,8,10-pentazatetracyclo[7.6.0.02,6.011,15]pentadeca-2(6),3,9-trien-7-one
• CAS: 191982-79-3
• 化学式: C₁₉H₂₁N₅O
• 分子量: 335.409
• InChiKey: PRCYQPWWULRKLG-KGLIPLIRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(bromomethyl)phenol 、 (6aR,9aS)-5-ethyl-5,6a,7,8,9,9a-hexahydro-2-(phenylmethyl)cyclopent[4,5]imidazo[2,1-b]purin-4(1H)-one 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (11R,15S)-4-benzyl-8-ethyl-5-[(4-hydroxyphenyl)methyl]-1,3,5,8,10-pentazatetracyclo[7.6.0.02,6.011,15]pentadeca-2(6),3,9-trien-7-one
  参考文献：
  名称：

  SAR development of polycyclic guanine derivatives targeted to the discovery of a selective PDE5 inhibitor for treatment of erectile dysfunction

  摘要：

  Development of structure-activity relationship of cyclic guanines I lead us to discovery of a potent and selective series of phosphodiesterase 5 inhibitors 52 59 (IC50 1.3-11.0 nM, PDE6/5 = 116-600). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.12.027
• 作为产物：
  描述：

  Ethyl 5-amino-1,2-dibenzylimidazole-4-carboxylate 在 palladium dihydroxide sodium methylate 、 ammonium formate 、 甲基磺酰氯 、 三乙胺 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 甲醇 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 55.5h， 生成 (6aR,9aS)-5-ethyl-5,6a,7,8,9,9a-hexahydro-2-(phenylmethyl)cyclopent[4,5]imidazo[2,1-b]purin-4(1H)-one
  参考文献：
  名称：

  Potent Tetracyclic Guanine Inhibitors of PDE1 and PDE5 Cyclic Guanosine Monophosphate Phosphodiesterases with Oral Antihypertensive Activity

  摘要：

  Tetracyclic guanines have been shown to be potent and selective inhibitors of the cGMP-hydrolyzing enzymes PDE1 and PDE5. In general, these compounds are inactive or only weakly active as inhibitors of PDE3, which is a major isozyme involved in cAMP hydrolysis. Structure-activity relationships are developed at N-1, C-2, N-3, and N-5 on the core nucleus. Compound 31, with an IC50 of 70 pM, is the most potent inhibitor of PDE1, while 50, with an IC50 of 4 nM, is the most potent inhibitor of PDE5. Compounds 20, 22, 30, and 50 are potent dual inhibitors with IC50 values below 30 nM for both PDE1 and PDE5. Compounds 12, 20, and 28 reduced blood pressure by more than 45 mmHg when administered orally at 10 mg/kg to the spontaneously hypertensive rat (SHR).

  DOI：

  10.1021/jm9608467

文献信息

• Potent Tetracyclic Guanine Inhibitors of PDE1 and PDE5 Cyclic Guanosine Monophosphate Phosphodiesterases with Oral Antihypertensive Activity
  作者：Ho-Sam Ahn、Ana Bercovici、George Boykow、Alan Bronnenkant、Samuel Chackalamannil、Jason Chow、Renee Cleven、John Cook、Michael Czarniecki、Carol Domalski、Ahmad Fawzi、Michael Green、Asli Gündes、Ginny Ho、Malvina Laudicina、Neil Lindo、Ke Ma、Mahua Manna、Brian McKittrick、Bita Mirzai、Terry Nechuta、Bernard Neustadt、Chester Puchalski、Kathryn Pula、Lisa Silverman、Elizabeth Smith、Andrew Stamford、Richard P. Tedesco、Hsingan Tsai、Deen Tulshian、Henry Vaccaro、Robert W. Watkins、Xiaoyu Weng、Joseph T. Witkowski、Yan Xia、Hongtao Zhang

  DOI：10.1021/jm9608467

  日期：1997.7.1

  Tetracyclic guanines have been shown to be potent and selective inhibitors of the cGMP-hydrolyzing enzymes PDE1 and PDE5. In general, these compounds are inactive or only weakly active as inhibitors of PDE3, which is a major isozyme involved in cAMP hydrolysis. Structure-activity relationships are developed at N-1, C-2, N-3, and N-5 on the core nucleus. Compound 31, with an IC50 of 70 pM, is the most potent inhibitor of PDE1, while 50, with an IC50 of 4 nM, is the most potent inhibitor of PDE5. Compounds 20, 22, 30, and 50 are potent dual inhibitors with IC50 values below 30 nM for both PDE1 and PDE5. Compounds 12, 20, and 28 reduced blood pressure by more than 45 mmHg when administered orally at 10 mg/kg to the spontaneously hypertensive rat (SHR).
• SAR development of polycyclic guanine derivatives targeted to the discovery of a selective PDE5 inhibitor for treatment of erectile dysfunction
  作者：Dmitri A Pissarnitski、Theodros Asberom、Craig D Boyle、Samuel Chackalamannil、Madhu Chintala、John W Clader、William J Greenlee、Yueqing Hu、Stanley Kurowski、Joyce Myers、Jairam Palamanda、Andrew W Stamford、Subbarao Vemulapalli、Yuguang Wang、Peng Wang、Ping Wu、Ruo Xu

  DOI：10.1016/j.bmcl.2003.12.027

  日期：2004.3

  Development of structure-activity relationship of cyclic guanines I lead us to discovery of a potent and selective series of phosphodiesterase 5 inhibitors 52 59 (IC50 1.3-11.0 nM, PDE6/5 = 116-600). (C) 2003 Elsevier Ltd. All rights reserved.