2,5-二脱氧腺苷 | 6698-26-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 2 '，5'-二脱氧核苷
• 中文名称: 2,5-二脱氧腺苷
• 英文名称: 2' 5'-dideoxyadenosine
• 英文别名: 2',5'-Dideoxyadenosine；2′,5′-dideoxyadenosine；2',5'-dideoxydenosine；2'5'-dideoxyadenosine；dideoxyadenosine；(2R,3S,5R)-5-(6-aminopurin-9-yl)-2-methyloxolan-3-ol
• CAS: 6698-26-6
• 化学式: C₁₀H₁₃N₅O₂
• 分子量: 235.246
• InChiKey: FFHPXOJTVQDVMO-DSYKOEDSSA-N

物化性质

• 沸点：
  547.0±60.0 °C(Predicted)
• 密度：
  1.77±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  99.1
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  -20°C

制备方法与用途

生物活性

2',5'-二脱氧腺苷（2',5'-Dideoxyadenosine）是一种有效且非竞争性的腺苷酸环化酶（adenylyl cyclase）抑制剂，能有效结合P位点，IC50为3 µM。这种核苷类似物在心脏中表现出强大的抗肾上腺素作用。

靶点

• IC50: 3 µM (腺苷酸环化酶)

体外研究

2',5'-二脱氧腺苷（10 μM，30 min）可以减少由乙酰胆碱（CCh）诱导的cAMP生成，并阻止谷氨酸A1受体在Ser845位点的磷酸化。此外，它还可以阻断由乙酰胆碱诱导的Akt的磷酸化增加，并减弱其引起的Ser2448磷酸化。2',5'-二脱氧腺苷（20-150 mM）像腺苷一样，依赖性和可逆性地抑制异丙肾上腺素（8-54 pmol）介导的正性肌力和心率效应，分别减少70%和50%。

Western Blot 分析

• 细胞系：原代海马神经元
• 浓度：10 μM
• 孵育时间：30 min
• 结果：减少了由乙酰胆碱诱导的cAMP生成，并阻止了谷氨酸A1受体在Ser845位点的磷酸化。

体内研究

2',5'-二脱氧腺苷（0.1 mg/kg，腹腔注射；预处理15 min）完全抑制了Fr•EtOAc在大鼠中的利尿、排钠及K+和Cl-保留作用。

反应信息

• 作为反应物：
  描述：

  2,5-二脱氧腺苷 在 叔丁基氯化镁 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 21.58h， 生成 2',5'-dd-3'AMPS
  参考文献：
  名称：

  Synthesis of Nucleoside 3′-Thiophosphates in One Step Procedure

  摘要：

  A mild and efficient one-step method of thiophosphorylation was devised for acid-sensitive nucleosides. The procedure is based on thiophosphorylation of nucleoside magnesium alkoxide by 2-chloro-2-thio-1,3,2-dioxaphospholane. The utility and efficiency of this method combined with deprotection of the resulting cyclic triester were demonstrated by its application to the synthesis of both adenosine 3'- and 5'-thiophosphates. The procedure does not require protection of the exocyclic amino group and can be successfully used for the thiophosphorylation of nucleosides that are unusually sensitive to depurination.

  DOI：

  10.1080/15257779908041610
• 作为产物：
  描述：

  (2S,3S,5R)-5-(6-Amino-9H-purin-9-yl)-2-((phenylthio)methyl)tetrahydrofuran-3-ol 在 镍 作用下， 以 甲醇 、 异丙醇 为溶剂， 反应 48.0h， 以72%的产率得到2,5-二脱氧腺苷
  参考文献：
  名称：

  Synthesis of 2′,5′-Dideoxy-adenosine-3′-monophosphate Derivatives as Allosteric Inhibitors of Adenylyl Cyclase

  摘要：

  The synthesis of a fluorescent and a lipophilic conjugate of 2',5'-dideoxy-3'AMP, an allosteric inhibitor of adenylyl cyclase, has been devised.

  DOI：

  10.1080/15257779508010705

文献信息

• Small organic molecules that increase the activity of Gelatinase A in ocular cells
  申请人：——

  公开号：US20040068017A1

  公开（公告）日：2004-04-08

  Small organic molecules capable of effecting a “pharmacological trabeculocanalotomy” in an eye by means of reducing juxtacanalicular meshwork as a barrier to outflow of aqueous. The small organic molecules increase Gelatinase A activity in ocular cells by increasing cell membrane expression of membrane-type matrix metalloproteinases (MT-MMPs) to increase aqueous outflow as a treatment for primary open angle glaucoma.

  能够通过减少近角网状结构作为截留眼内房水的屏障，从而在眼睛中实现“药理性梁切开术”的小有机分子。这些小有机分子通过增加眼细胞中明胶酶A的活性，通过增加细胞膜表达膜型基质金属蛋白酶（MT-MMPs）来增加房水流出，作为原发性开角青光眼的治疗。
• Synthesis of 6-Substituted 1-Deazapurine 2?-Deoxyribonucleosides
  作者：Thomas Wenzel、Frank Seela

  DOI：10.1002/hlca.19960790117

  日期：1996.2.7

  The synthesis of 6-substituted 1-deazapurine 2′-deoxyribonucleosides is described. Glycosylation of the 1-deazapurine (imidazo[4,5-b]pyridine) anions with the α-D-halogenose 5 gives stereoselectively N7- and N9- regioisomers. 1H-NMR NOE and 13C-NMR spectroscopy are used for unambiguous assignment of isomers, and 15N-NMR chemical shifts are correlated with σparaHammett constants and point charges.

  描述了6-取代的1-脱氮嘌呤2'-脱氧核糖核苷的合成。1-脱氮嘌呤（咪唑并[4,5-的糖基化b与α-d-halogenose]吡啶）阴离子5给出了立体选择性Ñ 7 -和Ñ 9 -区域异构体。1个H-NMR和NOE 13 C-NMR光谱法被用于异构体的明确分配，和15的N- NMR化学位移与σ相关段哈米特常数和点电荷。
• 9-Substituted adenine derivatives as prodrug regulators of cell and tissue function
  申请人：——

  公开号：US20040053825A1

  公开（公告）日：2004-03-18

  The present invention relates to 9-substituted adenine derivatives that inhibit adenylyl cyclase in cells but have little or no effect on isolated adenylyl cyclase. The derivatives are useful as prodrugs for inhibiting adenylyl cyclase and lowering 3′:5′-cAMP in cells, thereby inhibiting adenylyl cyclase dependent effects within cells.

  本发明涉及9-取代腺嘌呤衍生物，它们能抑制细胞中的腺苷酸环化酶，但对单独的腺苷酸环化酶几乎没有影响。这些衍生物可用作前药，用于抑制细胞中的腺苷酸环化酶并降低细胞中的3′：5′-cAMP，从而抑制细胞内腺苷酸环化酶依赖性效应。
• 9-substituted adenine derivatives as prodrug regulators of cell and tissue function
  申请人：The Research Foundation of State University of New York

  公开号：US07045309B2

  公开（公告）日：2006-05-16

  The present invention relates to 9-substituted adenine derivatives represented by formula (I) wherein W is selected from the group consisting of H, halogen, azido and amino group; X is selected from the group consisting of O, S, N(H), CH2, CH and C; Y is selected from the group consisting of H, hydroxy, C1-4 alkyl, C1-4 alkoxy and halogen; R is selected from the group consisting of H, hydroxymethyl, C1-4 alkyl, and C1-4 alkoxy; R1is selected from the group consisting of O, NH and CH2; R2represents a radical selected from the group consisting of —(CH2)n—S—C(O)—R4 and —(CH2)n—S—S—R4, where n=1-4 and R4is a C1-4-alkyl or aryl group and R4 is optionally substituted with a halogen, amino, N-alkylamino, N, N-dialkylamino or C1-4 alkoxy group and wherein each of the R2radicals may be the same or different; and R3is O or S. The derivatives are useful as prodrugs for inhibiting adenylyl cyclase and lowering 3′:5′-cAMP in cells, thereby inhibiting adenylyl cyclase dependent effects within cells.

  本发明涉及公式（I）所表示的9-取代腺嘌呤衍生物，其中W选自H，卤素，叠氮和氨基；X选自O，S，N（H），CH2，CH和C；Y选自H，羟基，C1-4烷基，C1-4烷氧基和卤素；R选自H，羟甲基，C1-4烷基和C1-4烷氧基；R1选自O，NH和CH2；R2表示从-（CH2）n-S-C（O）-R4和-（CH2）n-S-S-R4中选择的基团，其中n = 1-4，R4是C1-4烷基或芳基，并且R4可以选择性地被卤素，氨基，N-烷基氨基，N，N-二烷基氨基或C1-4烷氧基取代，其中每个R2基团可以相同或不同；R3为O或S。这些衍生物可用作前药，以抑制细胞中的腺苷酸酸化酶并降低3'：5'-cAMP，从而抑制细胞内腺苷酸酸化酶依赖性效应。
• COMPOSITION FOR CULTURING MULTIPOTENT STEM CELLS AND UTILIZATION OF THE SAME
  申请人：RIKEN

  公开号：EP1557461A1

  公开（公告）日：2005-07-27

  The invention aims to proliferate or establish undifferentiated pluripotent stem cells that retain their differentiation potency by culturing pluripotent stem cells in a medium free of a feeder cell, or a serum. The aim is attained by using a culture medium for pluripotent stem cells comprising the known ingredients, which is supplemented with an inhibitor of an adenylate cyclase activity.

  本发明旨在通过在不含饲养细胞或血清的培养基中培养多能干细胞，增殖或建立未分化的多能干细胞，以保持其分化潜能。本发明的目的是通过使用由已知成分组成的多能干细胞培养基，并辅以腺苷酸环化酶活性抑制剂来实现的。