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(1'R,2'S,4'S,5'S)-4-(2-iodo-6-methylamino-9H-purin-9-yl)-1-[(phosphato)methyl]-2-(phosphato)bicyclo[3.1.0]hexane | 779323-43-2

中文名称
——
中文别名
——
英文名称
(1'R,2'S,4'S,5'S)-4-(2-iodo-6-methylamino-9H-purin-9-yl)-1-[(phosphato)methyl]-2-(phosphato)bicyclo[3.1.0]hexane
英文别名
(1'R,2'S,4'S,5'S)-4-(2-iodo-6-methylamino-purin-9-yl)-1-[(phosphato)-methyl]-2-(phosphato)-bicyclo[3.1.0]hexane;2-iodo-N6-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate;2-iodo-N6-methyl-(N)-methanocarba-2'-deoxyadenosine 3',5'-bisphosphate;MRS2500;MRS 2500;[(1r,2s,4s,5s)-4-[2-Iodo-6-(Methylamino)-9h-Purin-9-Yl]-2-(Phosphonooxy)bicyclo[3.1.0]hex-1-Yl]methyl Dihydrogen Phosphate;[(1R,2S,4S,5S)-4-[2-iodo-6-(methylamino)purin-9-yl]-2-phosphonooxy-1-bicyclo[3.1.0]hexanyl]methyl dihydrogen phosphate
(1'R,2'S,4'S,5'S)-4-(2-iodo-6-methylamino-9H-purin-9-yl)-1-[(phosphato)methyl]-2-(phosphato)bicyclo[3.1.0]hexane化学式
CAS
779323-43-2
化学式
C13H18IN5O8P2
mdl
——
分子量
561.167
InChiKey
NMVWLEUONAKGCD-SMWKGLLFSA-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):
    -1.8
  • 重原子数:
    29
  • 可旋转键数:
    7
  • 环数:
    4.0
  • sp3杂化的碳原子比例:
    0.62
  • 拓扑面积:
    189
  • 氢给体数:
    5
  • 氢受体数:
    12

上下游信息

  • 上游原料
    中文名称 英文名称 CAS号 化学式 分子量

反应信息

  • 作为产物:
    参考文献:
    名称:
    Antiaggregatory activity in human platelets of potent antagonists of the P2Y1 receptor
    摘要:
    Activation of the P2Y(1) nucleotide receptor in platelets by ADP causes changes in shape and aggregation, mediated by activation of phospholipase C (PLC). Recently, MRS2500 (2-iodo-N-6-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate) was introduced as a highly potent and selective antagonist for this receptor. We have studied the actions of MRS2500 in human platelets and compared these effects with the effects of two acyclic nucleotide analogues, a bisphosphate MRS2298 and a bisphosphonate derivative MRS2496, which act as P2Y(1) receptor antagonists, although less potently than MRS2500. Improved synthetic methods for MRS2500 and MRS2496 were devised. The bisphosphonate is predicted to be more stable in general in biological systems than phosphate antagonists due to the non-hydrolyzable C-P bond. MRS2500 inhibited the ADP-induced aggregation of human platelets with an IC50 value of 0.95 nM. MRS2298 and MRS2496 also both inhibited the ADP-induced aggregation of human platelets with IC50 values of 62.8 nM and 1.5 muM, respectively. A similar order of potency was observed for the three antagonists in binding to the recombinant human P2Y(1) receptor and in inhibition of ADP-induced shape change and ADP-induced rise in intracellular Ca2+. No substantial antagonism of the pathway linked to the inhibition of cyclic AMP was observed for the nucleotide derivatives, indicating no interaction of these three P2Y(1) receptor antagonists with the proaggregatory P2Y(12) receptor, which is also activated by ADP. Thus, all three of the bisphosphate derivatives are highly selective antagonists of the platelet P2Y(1) receptor, and MRS2500 is the most potent such antagonist yet reported. (C) 2004 Elsevier Inc. All rights reserved.
    DOI:
    10.1016/j.bcp.2004.06.026
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文献信息

  • Compounds and methods for treating neurological and cardiovascular conditions
    申请人:Astrocyte Pharmaceuticals, Inc.
    公开号:US10265338B2
    公开(公告)日:2019-04-23
    The present invention relates to compounds and methods of use thereof for treatment of certain disorders and conditions, for example brain injuries such as stroke or traumatic brain injuries.
    本发明涉及用于治疗某些疾病和病症(例如脑损伤,如中风或脑外伤)的化合物及其使用方法。
  • 2-Substitution of Adenine Nucleotide Analogues Containing a Bicyclo[3.1.0]hexane Ring System Locked in a Northern Conformation:  Enhanced Potency as P2Y<sub>1</sub> Receptor Antagonists
    作者:Hak Sung Kim、Michihiro Ohno、Bin Xu、Hea Ok Kim、Yongseok Choi、Xiao D. Ji、Savitri Maddileti、Victor E. Marquez、T. Kendall Harden、Kenneth A. Jacobson
    DOI:10.1021/jm030127+
    日期:2003.11.1
    Preference for the northern (N) ring conformation of the ribose moiety of adenine nucleotide 3',5'-bisphosphate antagonists of P2Y(1), receptors was established by using a ring-constrained methanocarba (a bicyclo[3.1.0]hexane) ring as a ribose substitute (Nandanan et al. J. Med. Chem. 2000, 43, 829-842). We have now combined the ring-constrained (N)-methanocarba modification with other functionalities at the 2-position of the adenine moiety. A new synthetic route to this series of bisphosphate derivatives was introduced, consisting of phosphorylation of the pseudoribose moiety prior to coupling with the adenine base. The activity of the newly synthesized analogues was determined by measuring antagonism of 2-methylthio-ADP-stimulated phospholipase C (PLC) activity in 1321N1 human astrocytoma cells expressing the recombinant human P2Y(1), receptor and by using the radiolabeled antagonist [H-3](2)-chloro-N-6-methyl-(N)-methanocarba-2'-deoxyadenosine 3',5'-bisphosphate 5 in a newly developed binding assay in Sf9 cell membranes. Within the series of 2-halo analogues, the most potent molecule at the hP2Y(1) receptor was an (N)-methanocarba N-6-methyl-2-iodo analogue 12, which displayed a K-i value in competition for binding of [H-3]5 of 0.79 nM and a K-B value of 1.74 nM for inhibition of PLC. Thus, 12 is the most potent antagonist selective for the P2Y(1), receptor yet reported. The 2-iodo group was substituted with trimethyltin, thus providing a parallel synthetic route for the introduction of an iodo group in this high-affinity antagonist. The (N)-methanocarba-2-methylthio, 2-methylseleno, 2-hexyl, 2-(1-hexenyl), and 2-(l-hexynyl) analogues bound less well, exhibiting micromolar affinity at P2Y(1), receptors. An enzymatic method of synthesis of the 3',5'-bisphosphate from the corresponding 3'-monophosphate, suitable for the preparation of a radiophosphorylated analogue, was explored.
  • COMPOUNDS AND METHODS FOR TREATING NEUROLOGICAL AND CARDIOVASCULAR CONDITIONS
    申请人:Astrocyte Pharmaceuticals, Inc.
    公开号:US20180021363A1
    公开(公告)日:2018-01-25
    The present invention relates to compounds and methods of use thereof for treatment of certain disorders and conditions, for example brain injuries such as stroke or traumatic brain injuries.
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