4-[(E)-2-(1,2,3,6-tetrahydro-1,3-dimethyl-5-nitro-2,6-dioxopyrimidin-4-yl)vinyl]benzoic acid | 1165949-60-9

• 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: 4-[(E)-2-(1,2,3,6-tetrahydro-1,3-dimethyl-5-nitro-2,6-dioxopyrimidin-4-yl)vinyl]benzoic acid
• 英文别名: 4-[(E)-2-(1,3-dimethyl-5-nitro-2,6-dioxopyrimidin-4-yl)ethenyl]benzoic acid
• CAS: 1165949-60-9
• 化学式: C₁₅H₁₃N₃O₆
• 分子量: 331.285
• InChiKey: FSWJYRVLWDVJEM-VMPITWQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-[(E)-2-(1,2,3,6-tetrahydro-1,3-dimethyl-5-nitro-2,6-dioxopyrimidin-4-yl)vinyl]benzoic acid 在 甲酸 、 sodium dithionite 作用下， 以80%的产率得到4-(2,3,4,5-tetrahydro-1,3-dimethyl-2,4-dioxo-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzoic acid
  参考文献：
  名称：

  1,3-Dialkyl-8-N-substituted benzyloxycarbonylamino-9-deazaxanthines as potent adenosine receptor ligands: Design, synthesis, structure–affinity and structure–selectivity relationships

  摘要：

  A number of 1,3-dialkyl-9-deazaxanthines (9-dAXs), bearing a variety of N-substituted benzyloxycarbonylamino substituents at position 8, were prepared and evaluated for their binding affinity to the recombinant human adenosine receptors (hARs), chiefly to the hA(2B) and hA(2A) AR subtypes. Several ligands endowed with excellent binding affinity to the hA2B receptors, but low selectivity versus hA2A and hA(1) were identified. Among these, 1,3-dimethyl-N-30-thienyl carbamate 15 resulted as the most potent ligand at hA(2B) (K-i = 0.8 nM), with a low selectivity versus hA(2A) (hA(2A)/hA(2B) = 12.6) and hA(1) (hA(1)/hA(2B) = 12.5) and a higher selectivity versus hA(3) (hA(3)/hA(2B) = 454). When tested in functional assays in vitro, compound 15 exhibited high antagonist activities and efficacies versus both the A(2A) and A(2B) receptor subtypes, with pA(2) values close to the corresponding pK(i)s. A comparative analysis of structure - affinity and structure selectivity relationships of the similar analogues 8-N-substituted benzyloxycarbonylamino- and 8-N-substituted phenoxyacetamido-9-dAXs suggested that their binding modes at the hA(2B) and hA(2A) ARs may strongly differ. Computational studies help to clarify this striking difference arising from a simple, albeit crucial, structural change, from CH2OCON to OCH2CON, in the para-position of the 8-phenyl ring. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.03.062
• 作为产物：
  描述：

  1,3,6-三甲基-5-硝基-2,4(1H,3H)-嘧啶二酮 、 对醛基苯甲酸 在 哌啶 作用下， 以 1,4-二氧六环 为溶剂， 以70%的产率得到4-[(E)-2-(1,2,3,6-tetrahydro-1,3-dimethyl-5-nitro-2,6-dioxopyrimidin-4-yl)vinyl]benzoic acid
  参考文献：
  名称：

  1,3-Dialkyl-8-N-substituted benzyloxycarbonylamino-9-deazaxanthines as potent adenosine receptor ligands: Design, synthesis, structure–affinity and structure–selectivity relationships

  摘要：

  A number of 1,3-dialkyl-9-deazaxanthines (9-dAXs), bearing a variety of N-substituted benzyloxycarbonylamino substituents at position 8, were prepared and evaluated for their binding affinity to the recombinant human adenosine receptors (hARs), chiefly to the hA(2B) and hA(2A) AR subtypes. Several ligands endowed with excellent binding affinity to the hA2B receptors, but low selectivity versus hA2A and hA(1) were identified. Among these, 1,3-dimethyl-N-30-thienyl carbamate 15 resulted as the most potent ligand at hA(2B) (K-i = 0.8 nM), with a low selectivity versus hA(2A) (hA(2A)/hA(2B) = 12.6) and hA(1) (hA(1)/hA(2B) = 12.5) and a higher selectivity versus hA(3) (hA(3)/hA(2B) = 454). When tested in functional assays in vitro, compound 15 exhibited high antagonist activities and efficacies versus both the A(2A) and A(2B) receptor subtypes, with pA(2) values close to the corresponding pK(i)s. A comparative analysis of structure - affinity and structure selectivity relationships of the similar analogues 8-N-substituted benzyloxycarbonylamino- and 8-N-substituted phenoxyacetamido-9-dAXs suggested that their binding modes at the hA(2B) and hA(2A) ARs may strongly differ. Computational studies help to clarify this striking difference arising from a simple, albeit crucial, structural change, from CH2OCON to OCH2CON, in the para-position of the 8-phenyl ring. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.03.062

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。
• 1,3-Dialkyl-8-N-substituted benzyloxycarbonylamino-9-deazaxanthines as potent adenosine receptor ligands: Design, synthesis, structure–affinity and structure–selectivity relationships
  作者：Franco Fernández、Olga Caamaño、M. Isabel Nieto、Carmen López、Xerardo García-Mera、Angela Stefanachi、Orazio Nicolotti、M. Isabel Loza、Jose Brea、Cristina Esteve、Victor Segarra、Bernat Vidal、Angelo Carotti

  DOI：10.1016/j.bmc.2009.03.062

  日期：2009.5

  A number of 1,3-dialkyl-9-deazaxanthines (9-dAXs), bearing a variety of N-substituted benzyloxycarbonylamino substituents at position 8, were prepared and evaluated for their binding affinity to the recombinant human adenosine receptors (hARs), chiefly to the hA(2B) and hA(2A) AR subtypes. Several ligands endowed with excellent binding affinity to the hA2B receptors, but low selectivity versus hA2A and hA(1) were identified. Among these, 1,3-dimethyl-N-30-thienyl carbamate 15 resulted as the most potent ligand at hA(2B) (K-i = 0.8 nM), with a low selectivity versus hA(2A) (hA(2A)/hA(2B) = 12.6) and hA(1) (hA(1)/hA(2B) = 12.5) and a higher selectivity versus hA(3) (hA(3)/hA(2B) = 454). When tested in functional assays in vitro, compound 15 exhibited high antagonist activities and efficacies versus both the A(2A) and A(2B) receptor subtypes, with pA(2) values close to the corresponding pK(i)s. A comparative analysis of structure - affinity and structure selectivity relationships of the similar analogues 8-N-substituted benzyloxycarbonylamino- and 8-N-substituted phenoxyacetamido-9-dAXs suggested that their binding modes at the hA(2B) and hA(2A) ARs may strongly differ. Computational studies help to clarify this striking difference arising from a simple, albeit crucial, structural change, from CH2OCON to OCH2CON, in the para-position of the 8-phenyl ring. (C) 2009 Elsevier Ltd. All rights reserved.