6-[4-[1-(4,4-diphenylpiperidin-1-yl)-2-methyl-1-oxopropan-2-yl]oxyphenyl]-3-methyl-1-propyl-5H-pyrrolo[3,2-d]pyrimidine-2,4-dione | 1029402-14-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-[4-[1-(4,4-diphenylpiperidin-1-yl)-2-methyl-1-oxopropan-2-yl]oxyphenyl]-3-methyl-1-propyl-5H-pyrrolo[3,2-d]pyrimidine-2,4-dione
• CAS: 1029402-14-9
• 化学式: C₃₇H₄₀N₄O₄
• 分子量: 604.749
• InChiKey: PQGFYLALPAFRFB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  45
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  86
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-methyl-2-(4-(3-methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)phenoxy)propanoic acid 、 4-N-甲基苄基-n-乙氧甲酰哌啶双盐酸盐 在 polymer-bound morpholine 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以45%的产率得到6-[4-[1-(4,4-diphenylpiperidin-1-yl)-2-methyl-1-oxopropan-2-yl]oxyphenyl]-3-methyl-1-propyl-5H-pyrrolo[3,2-d]pyrimidine-2,4-dione
  参考文献：
  名称：

  1-, 3- and 8-substituted-9-deazaxanthines as potent and selective antagonists at the human A2B adenosine receptor

  摘要：

  A large series of piperazin-, piperidin- and tetrahydroisoquinolinamides of 4-(1,3-dialkyl-9-deazaxanthin-8-yl)phenoxyacetic acid were prepared through conventional or multiple parallel syntheses and evaluated for their binding affinity at the recombinant human adenosine receptors, chiefly at the hA(2B) and hA(2A) receptor subtypes. Several ligands endowed with high binding affinity at hA(2B) receptors, excellent selectivity over hA(2A) and hA(3) and a significant, but lower, selectivity over hA(1) were identified. Among them, piperazinamide derivatives 23 and 52, and piperidinamide derivative 69 proved highly potent at hA2B (K-i = 11, 2 and 5.5 nM, respectively) and selective towards hA(2A) (hA(2A)/hA(2B) SI = 912, 159 and 630, respectively), hA(3) (hA(3)/hA(2B) SI = > 100, 3090 and >180, respectively) and hA(1) (hA(1)/hA(2B) SI = > 100, 44 and 120, respectively), SI being the selectivity index. A number of selected ligands tested in functional assays in vitro showed very interesting antagonist activities and efficacies at both A(2A) and A(2B) receptor subtypes, with pA(2) values close to the corresponding pK(i)s. Structure-affinity and structure-selectivity relationships suggested that the binding potency at the hA(2B) receptor may be increased by lipophilic substituents at the N4-position of piperazinamides and that an ortho-methoxy substituent at the 8-phenyl ring and alkyl groups at NI larger than the ones at N3, in the 9-deazaxanthine ring, may strongly enhance the hA(2A)/hA(2B) SI. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.01.002

文献信息

• 1-, 3- and 8-substituted-9-deazaxanthines as potent and selective antagonists at the human A2B adenosine receptor
  作者：Angela Stefanachi、Jose Manuel Brea、Maria Isabel Cadavid、Nuria B. Centeno、Cristina Esteve、Maria Isabel Loza、Ana Martinez、Rosa Nieto、Enrique Raviña、Ferran Sanz

  DOI：10.1016/j.bmc.2008.01.002

  日期：2008.3.15

  A large series of piperazin-, piperidin- and tetrahydroisoquinolinamides of 4-(1,3-dialkyl-9-deazaxanthin-8-yl)phenoxyacetic acid were prepared through conventional or multiple parallel syntheses and evaluated for their binding affinity at the recombinant human adenosine receptors, chiefly at the hA(2B) and hA(2A) receptor subtypes. Several ligands endowed with high binding affinity at hA(2B) receptors, excellent selectivity over hA(2A) and hA(3) and a significant, but lower, selectivity over hA(1) were identified. Among them, piperazinamide derivatives 23 and 52, and piperidinamide derivative 69 proved highly potent at hA2B (K-i = 11, 2 and 5.5 nM, respectively) and selective towards hA(2A) (hA(2A)/hA(2B) SI = 912, 159 and 630, respectively), hA(3) (hA(3)/hA(2B) SI = > 100, 3090 and >180, respectively) and hA(1) (hA(1)/hA(2B) SI = > 100, 44 and 120, respectively), SI being the selectivity index. A number of selected ligands tested in functional assays in vitro showed very interesting antagonist activities and efficacies at both A(2A) and A(2B) receptor subtypes, with pA(2) values close to the corresponding pK(i)s. Structure-affinity and structure-selectivity relationships suggested that the binding potency at the hA(2B) receptor may be increased by lipophilic substituents at the N4-position of piperazinamides and that an ortho-methoxy substituent at the 8-phenyl ring and alkyl groups at NI larger than the ones at N3, in the 9-deazaxanthine ring, may strongly enhance the hA(2A)/hA(2B) SI. (C) 2008 Elsevier Ltd. All rights reserved.