5’-羧基-2-氯-2’-3’-O-异亚丙基腺苷酸 | 72209-19-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: 5’-羧基-2-氯-2’-3’-O-异亚丙基腺苷酸
• 英文名称: 2-chloro-2',3'-O-isopropylideneadenosine-5'-carboxylic acid
• 英文别名: (3aR,4R,6R,6aR)-6-(6-amino-2-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuran[3,4-d][1,3]dioxol-4-ylcarboxylic acid；(3aS,4S,6R,6aR)-6-(6-Amino-2-chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxole-4-carboxylic acid；2',3'-O-isopropylidene-2-chloro-adenosine-5'-carboxylic acid；2-chloroadenosine-5'-carboxy-2',3'-O-isopropylidene；(3aS,4S,6R,6aR)-6-(6-amino-2-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylic acid；(3aR,4R,6S,6aS)-4-(6-amino-2-chloropurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carboxylic acid
• CAS: 72209-19-9
• 化学式: C₁₃H₁₄ClN₅O₅
• 分子量: 355.738
• InChiKey: AAIOFNJSAFFWKY-HEZDBXPZSA-N

物化性质

• 熔点：
  250-253 °C
• 沸点：
  610.0±65.0 °C(Predicted)
• 密度：
  2.01±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  135
• 氢给体数：
  2
• 氢受体数：
  9

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  应存放在2-8°C的环境中，避免光照，并保存在惰性气体中。

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
  ——	2-chloro-2',3'-O-isopropylideneadenosine	24639-06-3	C13H16ClN5O4	341.754
  2-氯腺嘌呤核苷	2-Chloroadenosine	146-77-0	C10H12ClN5O4	301.689

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  2-氯-2,3-o-异亚丙基腺苷酸-5-n-乙基羧酰胺	2-chloro-2',3'-O-isopropylideneadenosine-5'-N-ethylcarboxamide	120225-75-4	C15H19ClN6O4	382.807
  ——	2-chloro-2',3'-O-isopropylideneadenosine-5'-N-Boc-ornithineamide t-butyl ester	1414780-55-4	C26H38ClN7O8	612.083
  ——	2-chloroadenosine-5'-N-methyl uronamide	127258-30-4	C11H13ClN6O4	328.715
  ——	2-<<4-<2-(tert-butoxycarbonyl)etyl>phenethyl>amino>-2',3'-O-isopropylideneadenosine-5'-N-ethylcarboxamide	120225-76-5	C30H41N7O6	595.699
  ——	2-chloro-adenosine-5'-N-ethylcarboxamide	72209-22-4	C12H15ClN6O4	342.742
  ——	2-chloroadenosine-5'-N-ornithineamide	1414780-37-2	C14H18ClN7O6	415.793
  ——	(2S,3S,4R,5R)-5-[6-amino-2-(2-phenylethylamino)purin-9-yl]-3,4-dihydroxy-N-methyloxolane-2-carboxamide	120225-61-8	C19H23N7O4	413.436
  ——	(2S,3S,4R,5R)-5-[6-amino-2-(hexylamino)purin-9-yl]-N-butyl-3,4-dihydroxyoxolane-2-carboxamide	864062-00-0	C20H33N7O4	435.527
  (2S,3S,4R,5R)-5-[6-氨基-2-(2-苯基乙基氨基)嘌呤-9-基]-N-乙基-3,4-二羟基四氢呋喃-2-甲酰胺	CGS 21577	120225-53-8	C20H25N7O4	427.463
  ——	(2S,3S,4R,5R)-5-[6-amino-2-[2-(4-fluorophenyl)ethylamino]purin-9-yl]-N-ethyl-3,4-dihydroxyoxolane-2-carboxamide	120225-58-3	C20H24FN7O4	445.453

反应信息

• 作为反应物：
  描述：

  5’-羧基-2-氯-2’-3’-O-异亚丙基腺苷酸 在 氯化亚砜 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 2-氯-2,3-o-异亚丙基腺苷酸-5-n-乙基羧酰胺
  参考文献：
  名称：

  2-(Arylalkylamino)adenosin-5'-uronamides: a new class of highly selective adenosine A2 receptor ligands

  摘要：

  The synthesis and receptor-binding profiles at adenosine receptor subtypes for a series of 2-(arylalkylamino)-adenosin-5'-uronamides is described. Halogenated 2-phenethylamino analogues such as 3e show greater than 200-fold selectivity for the A2 receptor subtype on the basis of rat brain receptor binding. The general structure-activity relationship of this series of compounds is discussed both in terms of potency at A2 receptors as well as receptor subtype selectivity. It is possible to introduce a hydrophilic carboxyalkyl substituent to this series such as in CGS 21680A (3h) and still retain good potency and selectivity for A2 receptors. In addition, functional data in a perfused working rat heart model shows that these compounds possess full agonist properties at A2 receptors with 3h having a greater than 1500-fold separation between A2 (coronary vasodilatory) and A1 (negative chronotropic) receptor mediated events.

  DOI：

  10.1021/jm00169a015
• 作为产物：
  描述：

  2-氯腺嘌呤核苷 在 氢氧化钾 、 potassium permanganate 、 camphor-10-sulfonic acid 作用下， 以 水 、 丙酮 为溶剂， 反应 88.0h， 生成 5’-羧基-2-氯-2’-3’-O-异亚丙基腺苷酸
  参考文献：
  名称：

  2-(Arylalkylamino)adenosin-5'-uronamides: a new class of highly selective adenosine A2 receptor ligands

  摘要：

  The synthesis and receptor-binding profiles at adenosine receptor subtypes for a series of 2-(arylalkylamino)-adenosin-5'-uronamides is described. Halogenated 2-phenethylamino analogues such as 3e show greater than 200-fold selectivity for the A2 receptor subtype on the basis of rat brain receptor binding. The general structure-activity relationship of this series of compounds is discussed both in terms of potency at A2 receptors as well as receptor subtype selectivity. It is possible to introduce a hydrophilic carboxyalkyl substituent to this series such as in CGS 21680A (3h) and still retain good potency and selectivity for A2 receptors. In addition, functional data in a perfused working rat heart model shows that these compounds possess full agonist properties at A2 receptors with 3h having a greater than 1500-fold separation between A2 (coronary vasodilatory) and A1 (negative chronotropic) receptor mediated events.

  DOI：

  10.1021/jm00169a015

文献信息

• FLUORESCENT MOLECULAR PROBES FOR USE IN ASSAYS THAT MEASURE TEST COMPOUND COMPETITIVE BINDING WITH SAM-UTILIZING PROTEINS
  申请人：Barrett Stephen Douglas

  公开号：US20120295283A1

  公开（公告）日：2012-11-22

  Assay methods may generally comprise forming homogeneous assay mixtures comprising target SAM-utilizing protein, fluorescent detection analyte, and test compound, incubating, and measuring FP or TR-FRET signal emitted in order to determine a measure of test compound-SAM-utilizing protein binding. Assay mixtures comprise a SAM-utilizing protein, and a fluorescent detection analyte that binds with the SAM-utilizing protein in the absence of test compound. Assay mixtures may further comprise a test compound. Assay mixture embodiments may generate FP or TR-FRET signal properties that are a function of the inherent binding interactions of both the test compound and the detection analyte with the SAM-utilizing protein. Fluorescent detection analytes comprise a fluorophore moiety, a covalent linker moiety, and a SAM-utilizing protein ligand moiety and could be utilized in FP or TR-FRET assays to measure test compound binding.

  检测方法通常包括形成均质的检测混合物，其中包括目标SAM利用蛋白、荧光检测分析物和测试化合物，孵育，并测量发射的FP或TR-FRET信号，以确定测试化合物-SAM利用蛋白结合的度量。检测混合物包括SAM利用蛋白和荧光检测分析物，在没有测试化合物的情况下与SAM利用蛋白结合。检测混合物还可以包括测试化合物。检测混合物的实施形式可以生成FP或TR-FRET信号特性，这些特性是测试化合物和检测分析物与SAM利用蛋白固有结合相互作用的函数。荧光检测分析物包括荧光团、共价连接物和SAM利用蛋白配体团，可以用于FP或TR-FRET检测来测量测试化合物的结合。
• [EN] ADENOSINE A3 RECEPTOR AGONIST, PREPARATION METHOD THEREFOR, AND USE THEREOF<br/>[FR] AGONISTE RÉCEPTEUR A3 DE L'ADÉNOSINE, PROCÉDÉ DE PRÉPARATION ASSOCIÉ ET UTILISATION ASSOCIÉE<br/>[ZH] A3腺苷受体激动剂及其制备方法和用途
  申请人：[en]ZHEJIANG VIMGREEN PHARMACEUTICALS, LTD;[zh]浙江春禾医药科技有限公司

  公开号：WO2022143740A1

  公开（公告）日：2022-07-07

  提供了一种对A3腺苷受体活性既有调节或激动作用的化合物，该系列化合物的制备方法，该系列化合物的药物组合物，以及该系列化合物的医药用途。该系列化合物可以作为高效的A3腺苷受体激动剂，具有抗肿瘤、抗炎、止痛、神经保护、心肌防护、眼疾治疗和抗感染等多种药理活性。
• [EN] ADENOSINE RECEPTOR AGONISTS<br/>[FR] COMPOSES THERAPEUTIQUES
  申请人：CAMBRIDGE BIOTECHNOLOGY LTD

  公开号：WO2005084653A3

  公开（公告）日：2006-05-18
• An Fc Domain Protein–Small Molecule Conjugate as an Enhanced Immunomodulator
  作者：Meng-Jung Chiang、Marc A. Holbert、Jay H. Kalin、Young-Hoon Ahn、John Giddens、Mohammed N. Amin、Martin S. Taylor、Samuel L. Collins、Yee Chan-Li、Adam Waickman、Po-Yuan Hsiao、David Bolduc、Daniel J. Leahy、Maureen R. Horton、Lai-Xi Wang、Jonathan D. Powell、Philip A. Cole

  DOI：10.1021/ja5006674

  日期：2014.3.5

  Proteins as well as small molecules have demonstrated success as therapeutic agents, but their pharmacologic properties sometimes fall short against particular drug targets. Although the adenosine 2a receptor (A(2A)R) has been identified as a promising target for immunotherapy, small molecule A(2A)R agonists have suffered from short pharmacokinetic half-lives and the potential for toxicity by modulating nonimmune pathways. To overcome these limitations, we have tethered the AR agonist CGS-21680 to the immunoglobulin Fc domain using expressed protein ligation with Sf9 cell secreted protein. The protein small molecule conjugate Fc-CGS retained potent Fc receptor and A(2A)R interactions and showed superior properties as a therapeutic for the treatment of a mouse model of autoimmune pneumonitis. This approach may provide a general strategy for optimizing small molecule therapeutics.
• HUTCHISON, ALAN J.;WILLIAMS, MICHAEL;JESUS, REYNALDA DE;RINA, YOKOYAMA;OE+, J. MED. CHEM., 33,(1990) N, C. 1919-1924
  作者：HUTCHISON, ALAN J.、WILLIAMS, MICHAEL、JESUS, REYNALDA DE、RINA, YOKOYAMA、OE+

  DOI：——

  日期：——