[4-(2,3,4,5-tetrahydro-1,3-dimethyl-2,4-dioxo-1H-pyrrolo[3,2-d]pyrimidin-6-yl)phenyl]methyl pyridin-2-ylcarbamate | 480993-85-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: [4-(2,3,4,5-tetrahydro-1,3-dimethyl-2,4-dioxo-1H-pyrrolo[3,2-d]pyrimidin-6-yl)phenyl]methyl pyridin-2-ylcarbamate
• 英文别名: [4-(1,3-dimethyl-2,4-dioxo-5H-pyrrolo[3,2-d]pyrimidin-6-yl)phenyl]methyl N-pyridin-2-ylcarbamate
• CAS: 480993-85-9
• 化学式: C₂₁H₁₉N₅O₄
• 分子量: 405.413
• InChiKey: HESPWNZEAPUVKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-[4-(hydroxymethyl)phenyl]-1,3-dimethyl-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione 、 2-异氰酸酯吡啶 以 1,4-二氧六环 为溶剂， 以60%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)phenyl]methyl pyridin-2-ylcarbamate
  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

• Compounds
  申请人：Browning Andrew

  公开号：US20050192339A1

  公开（公告）日：2005-09-01

  The invention relates to compounds of the general formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and X are as defined in the description, or pharmaceutically acceptable salts, hydrates, geometrical isomers, racemates, tautomers, optical isomers, N-oxides and prodrug forms thereof. The compounds may be used for the treatment or prophylaxis of disorders related to the MCH1R receptor and for modulation of appetite. The invention also relates to such use as well as to pharmaceutical formulations comprising a compound of formula (I).

  本发明涉及通式(I)的化合物，其中R1、R2、R3、R4、R5、R6、R7、R8和X如描述中所定义，或其药学上可接受的盐、水合物、几何异构体、外消旋体、互变异构体、光学异构体、N-氧化物和前药形式。这些化合物可用于治疗或预防与MCH1R受体有关的疾病，并用于调节食欲。本发明还涉及这种用途以及包含通式(I)化合物的制药配方。
• 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.