(11R,15S)-3-benzyl-4-methyl-8-propan-2-yl-1,3,5,8,10-pentazatetracyclo[7.6.0.02,6.011,15]pentadeca-2(6),4,9-trien-7-one | 1028282-46-3

• 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: (11R,15S)-3-benzyl-4-methyl-8-propan-2-yl-1,3,5,8,10-pentazatetracyclo[7.6.0.02,6.011,15]pentadeca-2(6),4,9-trien-7-one
• CAS: 1028282-46-3
• 化学式: C₂₁H₂₅N₅O
• 分子量: 363.462
• InChiKey: MBRMDXBMSVYFQQ-SJORKVTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  53.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (11R,15S)-3-benzyl-4-methyl-8-propan-2-yl-1,3,5,8,10-pentazatetracyclo[7.6.0.02,6.011,15]pentadeca-2(6),4,9-trien-7-one 在 palladium dihydroxide ammonium formate 作用下， 以 甲醇 为溶剂， 生成 (6aR,9aS)-5,6a,7,8,9,9a-hexahydro-2-methyl-5-(1-methylethyl)cyclopent[4,5]imidazo[2,1-b]purin-4(3H)-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
• 作为产物：
  描述：

  5-氨基-1-苄基-2-甲基-1H-咪唑-4-羧酸乙酯 在 sodium methylate 、 甲基磺酰氯 、 三乙胺 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 苯 为溶剂， 反应 76.0h， 生成 (11R,15S)-3-benzyl-4-methyl-8-propan-2-yl-1,3,5,8,10-pentazatetracyclo[7.6.0.02,6.011,15]pentadeca-2(6),4,9-trien-7-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).