6-(4-{2-[4-(4-Bromophenyl)piperazin-1-yl]-2-oxoethoxy}phenyl)-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione | 480993-49-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 6-(4-{2-[4-(4-Bromophenyl)piperazin-1-yl]-2-oxoethoxy}phenyl)-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione
• 英文别名: 6-[4-[2-[4-(4-bromophenyl)piperazin-1-yl]-2-oxoethoxy]phenyl]-1,3-dimethyl-5H-pyrrolo[3,2-d]pyrimidine-2,4-dione
• CAS: 480993-49-5
• 化学式: C₂₆H₂₆BrN₅O₄
• 分子量: 552.428
• InChiKey: WZUIISQBVTWPJF-UHFFFAOYSA-N

物化性质

• 沸点：
  803.9±75.0 °C(Predicted)
• 密度：
  1.476±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  89.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  [4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-phenoxy]-acetic acid 、 1-(4-溴苯基)哌嗪 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33%的产率得到6-(4-{2-[4-(4-Bromophenyl)piperazin-1-yl]-2-oxoethoxy}phenyl)-1,3-dimethyl-1,5-dihydropyrrolo[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

• 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。
• [EN] PROCESS FOR PREPARING BENZODIAZEPINES<br/>[FR] PROCEDE DE PREPARATION DE BENZODIAZEPINES
  申请人：ARROW THERAPEUTICS LTD

  公开号：WO2005090319A1

  公开（公告）日：2005-09-29

  A process for producing a compound which is a benzodiazepine derivative of formula: (I) wherein: represents or R1 represents C1-6 alkyl, aryl or heteroaryl; each R3 is the same or different and represents halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkyl, C1-6 haloalkoxy, amino, mono(C1-6 alkyl)amino, di(C1-6 alkyl)amino, nitro, cyano, -CO2R/, -CONR/R//, -NH-CO-R/, -S(O)R/, -S(O)2R/, -NH-S(O)2R/, -S(O)NR/R// or -S(O)2NR/R//, wherein each R/ and R// is the same or different and represents hydrogen or C1-6 alkyl; n is from 0 to 3; X represents -NH-, -N(C1-C6 alkyl)-, -CO-, -CO-NR/-, -S(O)- or -S(O)2-, wherein R/ is hydrogen or a C1-C6 alkyl group; and R4 represents hydrogen; or -CO-R4' or -CO-NH-R4', wherein R4' is a C1-C6 alkyl, C1-C6 hydroxyalkyl, aryl, heteroaryl, carbocyclyl or heterocyclyl group, which group is substituted by a C1-C6 hydroxyalkyl, aryl, heteroaryl, carbocyclyl or heterocyclyl group or a -(C1-C4 alkyl)-X1-(C1-C4 alkyl)-X2-(C1-C4 alkyl) group, wherein X1 represents -O-, -S- or -NR/-, wherein R/ represents H or a C1-C4 alkyl group and X2 represents -CO-, -SO- or -SO2-; or R4' represents -A1-Y-A2, wherein: Al is an aryl, heteroaryl, carbocyclyl or heterocyclyl group; Y represents a direct bond or a C1-C4 alkylene, -SO2-, -CO-, -O-, -S or -NR/-, wherein R/ is a C1-C6 alkyl group; and A2 is an aryl, heteroaryl, carbocyclyl or heterocyclyl group; or R4 is a group selected from aryl-C(O)-C(O)-, heteroaryl-C(O)-C(O)-, carbocyclyl-C(O)-C(O)-, heterocyclyl-C(O)-C(O)- and -ZR5, wherein: Z represents -CO-, -S(O)- or -S(O)2-; and R5 represents C1-6 alkyl, hydroxy, C1-6 alkoxy, C1-6 alkylthio, aryl, heteroaryl, carbocyclyl, heterocyclyl, aryl-(C1-6 alkyl)-, heteroaryl-(C1-6 alkyl)-, carbocyclyl-(C1-6 alkyl)-, heterocyclyl-(C1-6 alkyl)-, aryl-(C1-6 alkyl)-O-, heteroaryl-(C1-6 alkyl)-O-, carbocyclyl-(C1-6 alkyl)-O-, heterocyclyl-(C1-6 alkyl)-O- or -NR/R// wherein each R/ and R// is the same or different and represents hydrogen, C1-6 alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, aryl-(C1-6 alkyl)-, heteroaryl-(C1-6 alkyl)-, carbocyclyl-(C1-6 alkyl)- or heterocyclyl-(C1-6 alkyl)-; or a pharmaceutically acceptable salt thereof; which process comprises: (a) subjecting a racemic benzodiazepine derivative of formula: (IIa): wherein R1, R3, R4, n and X are as defined above, and R2 represents an amino protecting group, to crystallisation induced dynamic resolution to yield a benzodiazepine derivative of formula (II): wherein, R1, R2, R3, R4, n and X are as defined above; and (b) deprotecting the benzodiazepine derivative of formula (II) as defined above to yield a benzodiazepine derivative of formula (I) or a pharmaceutically acceptable form thereof as defined above.
• 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.