2-[4-(2,4-dioxo-1,3-dipropyl-5H-pyrrolo[3,2-d]pyrimidin-6-yl)phenoxy]-2-phenylacetic acid | 480994-31-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2-[4-(2,4-dioxo-1,3-dipropyl-5H-pyrrolo[3,2-d]pyrimidin-6-yl)phenoxy]-2-phenylacetic acid
• CAS: 480994-31-8
• 化学式: C₂₆H₂₇N₃O₅
• 分子量: 461.517
• InChiKey: ROEPPLWZZCOTGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[4-(2,4-dioxo-1,3-dipropyl-5H-pyrrolo[3,2-d]pyrimidin-6-yl)phenoxy]-2-phenylacetic acid 、 4-氟苯胺 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20%的产率得到2-[4-(2,4-dioxo-1,3-dipropyl-5H-pyrrolo[3,2-d]pyrimidin-6-yl)phenoxy]-N-(4-fluorophenyl)-2-phenylacetamide
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of 1-,3-,8-, and 9-Substituted-9-deazaxanthines at the Human A_2B Adenosine Receptor

  摘要：

  Over two hundred 1-, 3-, 8-, and 9-substituted-9-deazaxanthines were prepared and evaluated for their binding affinity at the recombinant human adenosine receptors, in particular at the hA(2B) and hA(2A) subtypes. Several ligands endowed with sub-micromolar to low nanomolar binding affinity at hA(2B) receptors, good selectivity over hA(2A) and hA(3), but a relatively poor selectivity over hA(1) were obtained. Good antagonistic potencies and efficacies, with pA(2) values close to the corresponding pK(i)s, were observed in functional assays in vitro performed on a selected series of compounds. 1,3-Dimethyl-8-phenoxy-(N-p-halogenophenyl)-acetamido-9-deazaxanthine derivatives appeared as the most interesting leads, some of them showing outstanding hA(2B) affinities, high selectivity over hA(2A) and hA(3), but low selectivity over hA(1). Structure-affinity relationships suggested that the binding potency at the hA(2B) receptor was mainly modulated by the steric (lipophilic) properties of the substituents at positions 1 and 3 and by the electronic and lipophilic characteristics of the substituents at position 8. A comparison among affinity and selectivity profiles of 9-deazaxanthines with the corresponding xanthines suggested some possible differences in their binding mode.

  DOI：

  10.1021/jm0506221
• 作为产物：
  描述：

  {4-[(E)-2-(5-Nitro-2,6-dioxo-1,3-dipropyl-1,2,3,6-tetrahydro-pyrimidin-4-yl)-vinyl]-phenoxy}-phenyl-acetic acid 在 甲酸 、 sodium dithionite 作用下， 以90%的产率得到2-[4-(2,4-dioxo-1,3-dipropyl-5H-pyrrolo[3,2-d]pyrimidin-6-yl)phenoxy]-2-phenylacetic acid
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of 1-,3-,8-, and 9-Substituted-9-deazaxanthines at the Human A_2B Adenosine Receptor

  摘要：

  Over two hundred 1-, 3-, 8-, and 9-substituted-9-deazaxanthines were prepared and evaluated for their binding affinity at the recombinant human adenosine receptors, in particular at the hA(2B) and hA(2A) subtypes. Several ligands endowed with sub-micromolar to low nanomolar binding affinity at hA(2B) receptors, good selectivity over hA(2A) and hA(3), but a relatively poor selectivity over hA(1) were obtained. Good antagonistic potencies and efficacies, with pA(2) values close to the corresponding pK(i)s, were observed in functional assays in vitro performed on a selected series of compounds. 1,3-Dimethyl-8-phenoxy-(N-p-halogenophenyl)-acetamido-9-deazaxanthine derivatives appeared as the most interesting leads, some of them showing outstanding hA(2B) affinities, high selectivity over hA(2A) and hA(3), but low selectivity over hA(1). Structure-affinity relationships suggested that the binding potency at the hA(2B) receptor was mainly modulated by the steric (lipophilic) properties of the substituents at positions 1 and 3 and by the electronic and lipophilic characteristics of the substituents at position 8. A comparison among affinity and selectivity profiles of 9-deazaxanthines with the corresponding xanthines suggested some possible differences in their binding mode.

  DOI：

  10.1021/jm0506221

文献信息

• 6-Phenyldihydropyrrolopyrimidinedione derivatives
  申请人：Vidal Juan Bernat

  公开号：US20050070558A1

  公开（公告）日：2005-03-31

  6-phenylpyrrolopyrimidinedione derivatives of the formula (I), and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , R 4 and R 5 are organic residues, L 1 is a spacer group and R 6 is C(O) NR 10 R 11 , —S(O) 2 NR 10 R 11 , ? —ON═CR 12 R 13 , or a heterocyclyl, aryl? or heteroaryl group, where R 10 , R 11 , R 12 and R 13 are organic residues, have therapeutic potential as A2 adenosine receptor inhibitors.

  式(I)的6-苯基吡咯嘧啶二酮衍生物及其药学上可接受的盐，其中R1、R2、R3、R4和R5均为有机残基，L1为间隔基，R6为C（O）NR10R11、—S（O）2NR10R11、？—ON═CR12R13或杂环基、芳基或杂芳基，其中R10、R11、R12和R13为有机残基，具有作为A2腺苷受体抑制剂的治疗潜力。
• Design, Synthesis, and Structure−Activity Relationships of 1-,3-,8-, and 9-Substituted-9-deazaxanthines at the Human A_2B Adenosine Receptor
  作者：Angelo Carotti、Maria Isabel Cadavid、Nuria B. Centeno、Cristina Esteve、Maria Isabel Loza、Ana Martinez、Rosa Nieto、Enrique Raviña、Ferran Sanz、Victor Segarra、Eddy Sotelo、Angela Stefanachi、Bernat Vidal

  DOI：10.1021/jm0506221

  日期：2006.1.1

  Over two hundred 1-, 3-, 8-, and 9-substituted-9-deazaxanthines were prepared and evaluated for their binding affinity at the recombinant human adenosine receptors, in particular at the hA(2B) and hA(2A) subtypes. Several ligands endowed with sub-micromolar to low nanomolar binding affinity at hA(2B) receptors, good selectivity over hA(2A) and hA(3), but a relatively poor selectivity over hA(1) were obtained. Good antagonistic potencies and efficacies, with pA(2) values close to the corresponding pK(i)s, were observed in functional assays in vitro performed on a selected series of compounds. 1,3-Dimethyl-8-phenoxy-(N-p-halogenophenyl)-acetamido-9-deazaxanthine derivatives appeared as the most interesting leads, some of them showing outstanding hA(2B) affinities, high selectivity over hA(2A) and hA(3), but low selectivity over hA(1). Structure-affinity relationships suggested that the binding potency at the hA(2B) receptor was mainly modulated by the steric (lipophilic) properties of the substituents at positions 1 and 3 and by the electronic and lipophilic characteristics of the substituents at position 8. A comparison among affinity and selectivity profiles of 9-deazaxanthines with the corresponding xanthines suggested some possible differences in their binding mode.