5-amino-7-[β-(4-benzyloxy)-phenylethyl]-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo-[1,5-c]pyrimidine | 188113-13-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 英文名称: 5-amino-7-[β-(4-benzyloxy)-phenylethyl]-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo-[1,5-c]pyrimidine
• 英文别名: 4-(Furan-2-yl)-10-[2-(4-phenylmethoxyphenyl)ethyl]-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaen-7-amine
• CAS: 188113-13-5
• 化学式: C₂₅H₂₁N₇O₂
• 分子量: 451.487
• InChiKey: WUDQVVRYXALCCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-amino-7-[β-(4-benzyloxy)-phenylethyl]-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo-[1,5-c]pyrimidine 在 palladium on activated charcoal 氢气 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 4.0h， 生成 5-amino-7-[β-(4-hydroxy)-phenylethyl]-2-(furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of a Second Generation of Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as Potent and Selective A_2A Adenosine Receptor Antagonists

  摘要：

  New A(2A) adenosine receptor antagonists in the series of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]-pyrimidines, bearing oxygenated substituents on the phenylalkyl chains on the 7-position, have been synthesized. The compounds were tested in binding and functional assays to evaluate affinity, potency, and selectivity for rat A(2A) compared to rat A(1) and human A(3) receptor subtypes. The most interesting compounds (5d,e,h) were tested also in binding to human A(1) and A(2A) adenosine receptors. They showed very good affinity (K-i = 0.94 nM for compound 5h) and interesting selectivity with respect to both rA(1) and hA(3) (compound 5h: rA(1)/rA(2A) = 787, hA(3)/rA(2A) > 10000) These important findings make this new series of compounds the first really selective for A(2A) adenosine receptors. Thermodynamic parameters were evaluated; all the tested compounds displayed an enthalpy-driven binding as expected for antagonists. Moreover, compound 5h showed a negative entropy value. The highly negative enthalpic and entropic contributions could mean that 5h fits very well in the binding site where, probably, an electrostatic interaction is present associated to a scarce solvent reorganization around the receptor binding site. These compounds deserve to be further developed to assess their potential for treatment of neurodegenerative disorders such as Parkinson's disease.

  DOI：

  10.1021/jm9708689
• 作为产物：
  描述：

  2-呋喃甲酰肼 在 N-甲基吡咯烷酮 、 盐酸 、 对甲苯磺酸 作用下， 反应 4.5h， 生成 5-amino-7-[β-(4-benzyloxy)-phenylethyl]-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo-[1,5-c]pyrimidine
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of a Second Generation of Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as Potent and Selective A_2A Adenosine Receptor Antagonists

  摘要：

  New A(2A) adenosine receptor antagonists in the series of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]-pyrimidines, bearing oxygenated substituents on the phenylalkyl chains on the 7-position, have been synthesized. The compounds were tested in binding and functional assays to evaluate affinity, potency, and selectivity for rat A(2A) compared to rat A(1) and human A(3) receptor subtypes. The most interesting compounds (5d,e,h) were tested also in binding to human A(1) and A(2A) adenosine receptors. They showed very good affinity (K-i = 0.94 nM for compound 5h) and interesting selectivity with respect to both rA(1) and hA(3) (compound 5h: rA(1)/rA(2A) = 787, hA(3)/rA(2A) > 10000) These important findings make this new series of compounds the first really selective for A(2A) adenosine receptors. Thermodynamic parameters were evaluated; all the tested compounds displayed an enthalpy-driven binding as expected for antagonists. Moreover, compound 5h showed a negative entropy value. The highly negative enthalpic and entropic contributions could mean that 5h fits very well in the binding site where, probably, an electrostatic interaction is present associated to a scarce solvent reorganization around the receptor binding site. These compounds deserve to be further developed to assess their potential for treatment of neurodegenerative disorders such as Parkinson's disease.

  DOI：

  10.1021/jm9708689

文献信息

• 1,2,4-TRIAZOLO 1,5-c]PYRIMIDINE HETEROCYCLIC ANALOGUES HAVING ANTAGONISTIC ACTIVITY ON ADENOSINE A 2a? RECEPTOR
  申请人：SCHERING CORPORATION

  公开号：EP0856003A1

  公开（公告）日：1998-08-05
• [EN] 1,2,4-TRIAZOLO[1,5-c]PYRIMIDINE HETEROCYCLIC ANALOGUES HAVING ANTAGONISTIC ACTIVITY ON ADENOSINE A2a RECEPTOR<br/>[FR] ANALOGUES HETEROCYCLIQUES DE 1,2,4-TRIAZOLO[1,5-c] PYRIMIDINE POSSEDANT UNE ACTIVITE ANTAGONISTE SUR LES RECEPTEURS D'ADENOSINE A2a
  申请人：SCHERING-PLOUGH S.P.A.

  公开号：WO1997005138A1

  公开（公告）日：1997-02-13

  (EN) The compounds of general formula (I), wherein A is a pyrazole, imidazole or triazole ring, R is formula (II), wherein R1 and R2, which are the same or different, are H, OH, halogen, C1-4 alkoxy, C1-4 alkyl, nitro, amino, cyano, C1-4 haloalkyl, C1-4 haloalkoxy, carboxy, carboxamido groups; moreover the OH group, together with one of R1 or R2, or R1 and R2, can form the methylenedioxy group -O-CH2-O-; n is an integer from 0 to 4, are useful as therapeutical agents.(FR) L'invention concerne les composés représentés par la formule (I) qui sont utiles en tant qu'agents thérapeutiques. Dans la formule (I) A est un noyau pirazole, imidazole ou triazole, R est représenté par la formule (II) dans laquelle R1 et R2, qui sont identiques ou différents, sont H, ou un groupe OH, halogène, C1-C4 alkoxy, C1-C4 alkyle, nitro, amino, cyano, C1-C4 haloalkyle, C1-C4 haloalkoxy, carboxy, carboxamido; le groupe OH peut en outre former, en association avec R1 ou R2, ou bien avec R1 et R2, le groupe méthylènedioxy -O-CH2-O-; n est un entier compris entre 0 et 4.
• Design, Synthesis, and Biological Evaluation of a Second Generation of Pyrazolo[4,3-<i>e</i>]-1,2,4-triazolo[1,5-<i>c</i>]pyrimidines as Potent and Selective A_2A Adenosine Receptor Antagonists
  作者：Pier Giovanni Baraldi、Barbara Cacciari、Giampiero Spalluto、Manuela Bergonzoni、Silvio Dionisotti、Ennio Ongini、Katia Varani、P. A. Borea

  DOI：10.1021/jm9708689

  日期：1998.6.1

  New A(2A) adenosine receptor antagonists in the series of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]-pyrimidines, bearing oxygenated substituents on the phenylalkyl chains on the 7-position, have been synthesized. The compounds were tested in binding and functional assays to evaluate affinity, potency, and selectivity for rat A(2A) compared to rat A(1) and human A(3) receptor subtypes. The most interesting compounds (5d,e,h) were tested also in binding to human A(1) and A(2A) adenosine receptors. They showed very good affinity (K-i = 0.94 nM for compound 5h) and interesting selectivity with respect to both rA(1) and hA(3) (compound 5h: rA(1)/rA(2A) = 787, hA(3)/rA(2A) > 10000) These important findings make this new series of compounds the first really selective for A(2A) adenosine receptors. Thermodynamic parameters were evaluated; all the tested compounds displayed an enthalpy-driven binding as expected for antagonists. Moreover, compound 5h showed a negative entropy value. The highly negative enthalpic and entropic contributions could mean that 5h fits very well in the binding site where, probably, an electrostatic interaction is present associated to a scarce solvent reorganization around the receptor binding site. These compounds deserve to be further developed to assess their potential for treatment of neurodegenerative disorders such as Parkinson's disease.