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MRS 3769 | 863202-31-7

中文名称
——
中文别名
——
英文名称
MRS 3769
英文别名
N*6*-Cycloheptyl-N*2*-phenyl-9H-purine-2,6-diamine;6-N-cycloheptyl-2-N-phenyl-7H-purine-2,6-diamine
MRS 3769化学式
CAS
863202-31-7
化学式
C18H22N6
mdl
——
分子量
322.413
InChiKey
YDYCGADXGCIRTH-UHFFFAOYSA-N
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

计算性质

  • 辛醇/水分配系数(LogP):
    4.6
  • 重原子数:
    24
  • 可旋转键数:
    4
  • 环数:
    4.0
  • sp3杂化的碳原子比例:
    0.39
  • 拓扑面积:
    78.5
  • 氢给体数:
    3
  • 氢受体数:
    5

反应信息

  • 作为反应物:
    描述:
    MRS 3769碘甲烷potassium carbonate 作用下, 以 N,N-二甲基甲酰胺 为溶剂, 反应 1.0h, 以86%的产率得到N*6*-Cycloheptyl-9-methyl-N*2*-phenyl-9H-purine-2,6-diamine
    参考文献:
    名称:
    “Reversine” and Its 2-Substituted Adenine Derivatives as Potent and Selective A3 Adenosine Receptor Antagonists
    摘要:
    The dedifferentiation agent "reversine" [2-(4-morpholinoanilino)-N-6-cyclohexyladenine 2] was found to be a moderately potent antagonist for the human A(3) adenosine receptor (AR) with a K-i value of 0.66 mu M. This result prompted an exploration of the structure-activity relationship of related derivatives, synthesized via sequential substitution of 6-chloro-2-fluoropurine with selected nucleophiles. Optimization of substituents at these two positions identified 2-(phenylamino)-N6-cyclohexyladenine (12), 2-(phenylamino)-N-6-cycloheptyladenine (19), and 2-phenylamino-N-6-endo-norbornyladenine (21) as potent A(3) AR ligands with K-i values of 51, 42, and 37 nM, respectively, with 30-200-fold selectivity in comparison to A(1) and A(2A) ARs. The most selective A(3) AR antagonist (> 200-fold) was 2-(phenyloxy)-N-6-cyclohexyladenine (22). 9-Methylation of 12, but not 19, was well-tolerated in A(3) AR binding. Extension of the 2-phenylamino group to 2-benzyl- and 2-(2-phenylethylamino) reduced affinity. In the series of 2-(phenylamino), 2-(phenyloxy), and 2-(phenylthio) substitutions, the order of affinity at the A(3) AR was oxy >= amino > thio. Selected derivatives, including reversine (K-B value of 466 nM via Schild analysis), competitively antagonized the functional effects of a selective A(3) AR agonist, i.e., inhibition of forskolin-stimulated cAMP production in stably transfected Chinese hamster ovary (CHO) cells. These results are in agreement with other studies suggesting the presence of a lipophilic pocket in the AR binding site that is filled by moderately sized cycloalkyl rings at the N-6 position of both adenine and adenosine derivatives. Thus, the compound series reported herein comprise an important new series of selective A(3) AR antagonists. We were unable to reproduce the dedifferentiation effect of reversine, previously reported, or to demonstrate any connection between A(3) AR antagonist effects and dedifferentiation.
    DOI:
    10.1021/jm050221l
  • 作为产物:
    描述:
    2-氟-6-氯嘌呤N,N-二异丙基乙胺 作用下, 以 乙醇正丁醇 为溶剂, 反应 48.0h, 生成 MRS 3769
    参考文献:
    名称:
    “Reversine” and Its 2-Substituted Adenine Derivatives as Potent and Selective A3 Adenosine Receptor Antagonists
    摘要:
    The dedifferentiation agent "reversine" [2-(4-morpholinoanilino)-N-6-cyclohexyladenine 2] was found to be a moderately potent antagonist for the human A(3) adenosine receptor (AR) with a K-i value of 0.66 mu M. This result prompted an exploration of the structure-activity relationship of related derivatives, synthesized via sequential substitution of 6-chloro-2-fluoropurine with selected nucleophiles. Optimization of substituents at these two positions identified 2-(phenylamino)-N6-cyclohexyladenine (12), 2-(phenylamino)-N-6-cycloheptyladenine (19), and 2-phenylamino-N-6-endo-norbornyladenine (21) as potent A(3) AR ligands with K-i values of 51, 42, and 37 nM, respectively, with 30-200-fold selectivity in comparison to A(1) and A(2A) ARs. The most selective A(3) AR antagonist (> 200-fold) was 2-(phenyloxy)-N-6-cyclohexyladenine (22). 9-Methylation of 12, but not 19, was well-tolerated in A(3) AR binding. Extension of the 2-phenylamino group to 2-benzyl- and 2-(2-phenylethylamino) reduced affinity. In the series of 2-(phenylamino), 2-(phenyloxy), and 2-(phenylthio) substitutions, the order of affinity at the A(3) AR was oxy >= amino > thio. Selected derivatives, including reversine (K-B value of 466 nM via Schild analysis), competitively antagonized the functional effects of a selective A(3) AR agonist, i.e., inhibition of forskolin-stimulated cAMP production in stably transfected Chinese hamster ovary (CHO) cells. These results are in agreement with other studies suggesting the presence of a lipophilic pocket in the AR binding site that is filled by moderately sized cycloalkyl rings at the N-6 position of both adenine and adenosine derivatives. Thus, the compound series reported herein comprise an important new series of selective A(3) AR antagonists. We were unable to reproduce the dedifferentiation effect of reversine, previously reported, or to demonstrate any connection between A(3) AR antagonist effects and dedifferentiation.
    DOI:
    10.1021/jm050221l
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文献信息

  • “Reversine” and Its 2-Substituted Adenine Derivatives as Potent and Selective A<sub>3</sub> Adenosine Receptor Antagonists
    作者:Melissa Perreira、Jian-kang Jiang、Athena M. Klutz、Zhan-Guo Gao、Asher Shainberg、Changrui Lu、Craig J. Thomas、Kenneth A. Jacobson
    DOI:10.1021/jm050221l
    日期:2005.7.1
    The dedifferentiation agent "reversine" [2-(4-morpholinoanilino)-N-6-cyclohexyladenine 2] was found to be a moderately potent antagonist for the human A(3) adenosine receptor (AR) with a K-i value of 0.66 mu M. This result prompted an exploration of the structure-activity relationship of related derivatives, synthesized via sequential substitution of 6-chloro-2-fluoropurine with selected nucleophiles. Optimization of substituents at these two positions identified 2-(phenylamino)-N6-cyclohexyladenine (12), 2-(phenylamino)-N-6-cycloheptyladenine (19), and 2-phenylamino-N-6-endo-norbornyladenine (21) as potent A(3) AR ligands with K-i values of 51, 42, and 37 nM, respectively, with 30-200-fold selectivity in comparison to A(1) and A(2A) ARs. The most selective A(3) AR antagonist (> 200-fold) was 2-(phenyloxy)-N-6-cyclohexyladenine (22). 9-Methylation of 12, but not 19, was well-tolerated in A(3) AR binding. Extension of the 2-phenylamino group to 2-benzyl- and 2-(2-phenylethylamino) reduced affinity. In the series of 2-(phenylamino), 2-(phenyloxy), and 2-(phenylthio) substitutions, the order of affinity at the A(3) AR was oxy >= amino > thio. Selected derivatives, including reversine (K-B value of 466 nM via Schild analysis), competitively antagonized the functional effects of a selective A(3) AR agonist, i.e., inhibition of forskolin-stimulated cAMP production in stably transfected Chinese hamster ovary (CHO) cells. These results are in agreement with other studies suggesting the presence of a lipophilic pocket in the AR binding site that is filled by moderately sized cycloalkyl rings at the N-6 position of both adenine and adenosine derivatives. Thus, the compound series reported herein comprise an important new series of selective A(3) AR antagonists. We were unable to reproduce the dedifferentiation effect of reversine, previously reported, or to demonstrate any connection between A(3) AR antagonist effects and dedifferentiation.
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