PSB-16 | 156547-49-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: PSB-16
• 英文别名: 8-cyclopentyl-3-(3-hydroxypropyl)-1-propyl-3,7-dihydropurine-2,6-dione；8-cyclopentyl-3-(3-hydroxypropyl)-1-propylxanthine；1-Propyl-3-(3-hydroxypropyl)-8-cyclopentylxanthine；8-cyclopentyl-3-(3-hydroxypropyl)-1-propyl-7H-purine-2,6-dione
• CAS: 156547-49-8
• 化学式: C₁₆H₂₄N₄O₃
• 分子量: 320.392
• InChiKey: JIMRXOSHDPMNSO-UHFFFAOYSA-N

物化性质

• 沸点：
  603.7±61.0 °C(Predicted)
• 密度：
  1.271±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  89.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(氟磺酰基)苯甲酰氯 、 PSB-16 以 1,4-二氧六环 为溶剂， 反应 12.0h， 以80%的产率得到3-Fluorosulfonyl-benzoic acid 3-(8-cyclopentyl-2,6-dioxo-1-propyl-1,2,6,7-tetrahydro-purin-3-yl)-propyl ester
  参考文献：
  名称：

  Substituted 1,3-Dipropylxanthines as Irreversible Antagonists of A1 Adenosine Receptors

  摘要：

  This report describes the synthesis of 29 xanthines containing a chemoreactive chloroaryl beta-chloroethylamino, alpha,beta-unsaturated carbonyl bromoacetyl, 3-(fluorosulfonyl)benzoyl, or 4-(fluorosulfonyl)benzoyl group as part of an exocyclic 1-, 3-, or 8-substituent. The xanthines inhibited the binding of [H-3]-8-cyclopentyl-1,3-dipropylxanthine ([H-3]CPX) to the A(1) adenosine receptor (A(1)AR) of DDT1 MF2 cells at IC(50)s in the low-nanomolar to low-micromolar range. Seven of the 29 analogues irreversibly inhibited the binding of [H-3]CPX without changing the K-D of that ligand; five were 1,3-dipropylxantines having the following reactive groups as 8-substituents: (bromoacetamido)methyl (24), (bromoacetamido)ethyl (25), (bromoacetamido)propyl (26), [4-(fluorosulfonyl)benzamido]methyl (33) or 3-[[4-(fluorosulfonyl)benzoyl]oxy]cyclopentyl (42). Both 8-cyclopentyl-3-[3-[[4-(fluorosulfonyl)benzoyl]oxy]propyl]-1-propylxanthine (53) and 8-cyclopentyl-3-bis[3-[[4-(fluorosulfonyl)benzoyl]oxy]propyl]xanthine (55) inhibited [H-3]CPX binding irreversibly. Five of the ligands, including 26, 33 (IC50 = 49 mu M), and 53 (IC50 = 9 mu M), antagonized the binding of [H-3]NECA to the A(2a)AR of PC12 cells, but unlike binding to the A(1)AR, binding to the A(2a)AR was completely reversible. The potency of 33 (IC50 = 2 mu M, 72% loss of CPX binding at 1 mu M) and 53 (IC50 - 0.01 mu M, 74% loss of CPX binding at 0.05 mu M) and their seletivity for the A(1)AR suggest that those two ligands may be useful in studies of the structure and function of that receptor.

  DOI：

  10.1021/jm00043a010
• 作为产物：
  描述：

  环戊酸 在 ammonium sulfate 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 六甲基二硅氮烷 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 64.0h， 生成 PSB-16
  参考文献：
  名称：

  Versatile, convenient synthesis of pyrimido[1,2,3-cd]purinediones

  摘要：

  The alkylation of 3-substituted cycloalkylcarboxamido-6-aminouraciI derivatives with 3-bromo-1-propanol followed by ring closure yields 1,3,8-trisubstituted xanthine derivatives bearing a polar hydroxyl group. Use of the more reactive 1,3-dibromopropane or homologous dibromoalkanes for the alkylation reaction results in simultaneous alkylation at N1 and the exocyclic amino group (N-6) yielding imidazo-, pyrimido- and diazepino-pyrimidine derivatives. The pyrimidopyrimidine derivatives can subsequently be cyclised using hexamethyldisilazane at high temperature affording an easy, convenient and general access to tricyclic pyrimido[1,2,3-cd]purinediones. Alternatively, 3-substituted 6-amino-5-benzylideneaminouraciI derivatives can be reacted with 1,3-dibromopropane followed by an oxidative cyclisation using thionyl chloride to obtain the desired tricyclic pyrimido[1,2,3-cd]purinediones, which are sterically fixed analogues of pharmacologically active purine derivatives. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(02)01485-0

文献信息

• [DE] UNSYMMETRISCH SUBSTITUIERTE XANTHINE MIT ADENOSINANTAGONISTISCHEN EIGENSCHAFTEN<br/>[EN] ASYMMETRICALLY SUBSTITUTED XANTHINE WITH ADENOSINE-ANTAGONISTIC PROPERTIES<br/>[FR] XANTHINE SUBSTITUEE ASYMETRIQUEMENT AYANT DES PROPRIETES ANTAGONISTES DE L'ADENOSINE
  申请人：BOEHRINGER INGELHEIM KG

  公开号：WO1994003456A1

  公开（公告）日：1994-02-17

  (DE) Die vorliegende Erfindung betrifft neue Xanthin-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel und ihre Verwendung als Zwischenverbindungen.(EN) New xanthine derivatives, a process for preparing the same and their use as medicaments are disclosed, as well as their use as intermediate compounds.(FR) L'invention concerne de nouveaux dérivés de xanthine, leur procédé de fabrication et leur utilisation comme médicaments, ainsi que leur utilisation comme composés intermédiaires.

  该发明涉及新型蒽醌衍生物、制备它们的方法以及它们用作药品和中间化合物的用途。...(此处截稿，完整翻译未提供)
• A₁ Adenosine Receptor Antagonists as Ligands for Positron Emission Tomography (PET) and Single-Photon Emission Tomography (SPET)
  作者：Marcus H. Holschbach、Thomas Fein、Christof Krummeich、Robert G. Lewis、Walter Wutz、Ulrich Schwabe、Dieter Unterlugauer、Ray A. Olsson

  DOI：10.1021/jm9705465

  日期：1998.2.1

  The high affinity of 8-cyclopentyl-1,3-dipropylxanthine (CPX) for the A(1) adenosine receptor (A(1)AR) provides a good lead for developing radioligands suitable for positron emission tomography (PET) and single-photon emission tomography (SPET). This study tested the hypothesis that the kinds of chemical modifications made in the synthesis of CPX analogues containing carbon-ii, fluorine-18, or radioiodine will not alter affinity for the A(1)AR. This report describes the synthesis and radioligand binding assays of unlabeled CPX analogues having methyl, 2-methoxyethyl, 2-fluoropropyl, or 3-fluoropropyl substituents, respectively, at either N-1 (13a-d) or N-3 (8a-d) or an (E)-3-iodoprop-2-en-1-yl substituent at N-3 (8f). Compounds 8d,f and 13b,d antagonized the binding of [H-3]CPX to the A(1)AR of rat brain with affinities similar to those of CPX; compound 8c was twice as potent as CPX. Analogues 8a,b and 13a were less potent than CPX, but for each the K-i of antagonism was greater than or equal to 0.5 nM. Attempts to iodinate the 8-(4-hydroxyphenyl) analogue of CPX failed, probably because the xanthine substituent strongly deactivated the phenol toward electrophilic iodination. In summary, several of the modifications of the propyl groups of CPX needed to produce ligands for imaging by PET and SPET preserve or enhance affinity for the A(1)AR.
• Fluorosulfonyl-Substituted Xanthines as Selective Irreversible Antagonists for the A₁-Adenosine Receptor
  作者：Anthony R. Beauglehole、Stephen P. Baker、Peter J. Scammells

  DOI：10.1021/jm000181f

  日期：2000.12.1

  FSCPX (1) has been reported to be a potent, selective, and irreversible antagonist for the A(1)-adenosine receptor (AR). To obtain an irreversible A(1)AR antagonist with potentially better stability and to further elucidate the effects of linker structure on the pharmacological characteristics, several new analogues were targeted in which the labile ester linkage of 1 was replaced by more stable functionalities. In particular, alkyl and:amide linkers between the xanthine pharmacophore and the reactive 4-fluorosulfonylphenyl group were explored. The data showed that the chemical composition of the linker affects the affinity and apparent irreversible binding to the A(1)AR. Overall, compound 23b appeared to have the most advantageous characteristics as a potential irreversible ligand for the A(1)AR. These include relatively high affinity for the A(1)AR. as compared to the A(2A)AR, concentration-dependent and selective apparent irreversible binding to the A(1)AR, and ease;of removal of unbound ligand from biological membranes. These :properties indicate that 23b has the potential to be a useful tool for further study of the structure and function of the A(1)AR.
• Synthesis and use of FSCPX, an irreversible adenosine A1 antagonist, as a ‘Receptor Knock-Down’ tool
  作者：Jacqueline E.van Muijlwijk-Koezen、Henk Timmerman、Richard P.van der Sluis、Andrea C van de Stolpe、Wiro M.P.B Menge、Margot W Beukers、Piet H van der Graaf、Miriam de Groote、Adriaan P IJzerman

  DOI：10.1016/s0960-894x(01)00069-5

  日期：2001.3

  A new preparative synthetic route for the irreversible adenosine A1 antagonist 8-cyclopentyl-3-N-[3-((3-(4-fluorosulphonyl)benzoyl)-oxy)-propyl]-1-N-propyl-xanthine (FSCPX, 1) is described. The availability of ample amounts of the irreversible antagonist FSCPX allowed us to use FSCPX as a research tool for adenosine A1 receptors in in vivo experiments. After verification of the irreversible antagonistic function of FSCPX in in vitro experiments, FSCPX was used successfully as a 'receptor knock-down' tool in in vivo experiments on conscious rats.
• Scammells Peter J., Baker Stephen P., Belardinelli Luiz, Olsson Ray A., J. Med. Chem, 37 (1994) N 17, S 2704-2712
  作者：Scammells Peter J., Baker Stephen P., Belardinelli Luiz, Olsson Ray A.

  DOI：——

  日期：——