(2R,3R,5S)-2-[6-(N-benzoylbenzamido)-2-nitro-9H-purin-9-yl]-5-[(benzoyloxy)methyl]oxolan-3-yl benzoate | 864062-07-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: (2R,3R,5S)-2-[6-(N-benzoylbenzamido)-2-nitro-9H-purin-9-yl]-5-[(benzoyloxy)methyl]oxolan-3-yl benzoate
• 英文别名: 3'-deoxy-tetrabenzoyl-2-nitro-adenosine；[(2S,4R,5R)-4-benzoyloxy-5-[6-(dibenzoylamino)-2-nitropurin-9-yl]oxolan-2-yl]methyl benzoate
• CAS: 864062-07-7
• 化学式: C₃₈H₂₈N₆O₉
• 分子量: 712.675
• InChiKey: BIIZFTWYIHVUHH-JVLQLMMJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  53
• 可旋转键数：
  11
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  189
• 氢给体数：
  0
• 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
  ——	N6,N6,2'-O,5'-O-tetrabenzoyl-3'-deoxyadenosine	66884-45-5	C38H29N5O7	667.678
  [(1R,2R,4R,5R)-2-(6-氨基嘌呤-9-基)-3,6-二氧杂双环[3.1.0]己烷-4-基]甲醇	9-(2,3-anhydro-β-D-ribofuranosyl)adenine	2627-64-7	C10H11N5O3	249.229
  腺苷	adenosine	58-61-7	C10H13N5O4	267.244
  虫草素	cordycepin	73-03-0	C10H13N5O3	251.245

反应信息

• 作为反应物：
  描述：

  (2R,3R,5S)-2-[6-(N-benzoylbenzamido)-2-nitro-9H-purin-9-yl]-5-[(benzoyloxy)methyl]oxolan-3-yl benzoate 在 四丁基氟化铵 作用下， 以 乙腈 为溶剂， 反应 0.67h， 以59%的产率得到(2R,3R,5S)-2-[6-(N-benzoylbenzamido)-2-fluoro-9H-purin-9-yl]-5-[(benzoyloxy)methyl]oxolan-3-yl benzoate
  参考文献：
  名称：

  Structure–Activity Relationships of Synthetic Cordycepin Analogues as Experimental Therapeutics for African Trypanosomiasis

  摘要：

  Novel methods for treatment of African trypanosomiasis, caused by infection with Trypanosoma brucei are needed. Cordycepin (3'-deoxyadenosine, la) is a powerful trypanocidal compound in vitro but is ineffective in vivo because of rapid metabolic,degradation by adenosine deaminase (ADA). We elucidated the structural moieties of cordycepin required for trypanocidal activity and designed analogues that retained trypanotoxicity while gaining resistance to ADA-mediated metabolism. 2-Fluorocordycepin (2-fluoro3'-deoxyadenosine, 1b) was identified as a selective, potent, and ADA-resistant trypanocidal compound that cured T. brucei infection in mice. Compound 1b is transported through the high affinity TbAT1/P2 adenosine transporter and is a substrate of T. b. brucei adenosine kinase. 1b has good preclinical properties suitable for an, oral drug, albeit a relatively short plasma half-life. We present a rapid and efficient synthesis of 2-halogenated cordycepins, also useful synthons. for the development of additional novel C2-substituted 3'-deoxyadenosine analogues to be evaluated in development of experimental therapeutics.

  DOI：

  10.1021/jm401530a
• 作为产物：
  描述：

  虫草素 在 吡啶 、 四丁基硝酸铵 、 三氟乙酸酐 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 (2R,3R,5S)-2-[6-(N-benzoylbenzamido)-2-nitro-9H-purin-9-yl]-5-[(benzoyloxy)methyl]oxolan-3-yl benzoate
  参考文献：
  名称：

  Structure–Activity Relationships of Synthetic Cordycepin Analogues as Experimental Therapeutics for African Trypanosomiasis

  摘要：

  Novel methods for treatment of African trypanosomiasis, caused by infection with Trypanosoma brucei are needed. Cordycepin (3'-deoxyadenosine, la) is a powerful trypanocidal compound in vitro but is ineffective in vivo because of rapid metabolic,degradation by adenosine deaminase (ADA). We elucidated the structural moieties of cordycepin required for trypanocidal activity and designed analogues that retained trypanotoxicity while gaining resistance to ADA-mediated metabolism. 2-Fluorocordycepin (2-fluoro3'-deoxyadenosine, 1b) was identified as a selective, potent, and ADA-resistant trypanocidal compound that cured T. brucei infection in mice. Compound 1b is transported through the high affinity TbAT1/P2 adenosine transporter and is a substrate of T. b. brucei adenosine kinase. 1b has good preclinical properties suitable for an, oral drug, albeit a relatively short plasma half-life. We present a rapid and efficient synthesis of 2-halogenated cordycepins, also useful synthons. for the development of additional novel C2-substituted 3'-deoxyadenosine analogues to be evaluated in development of experimental therapeutics.

  DOI：

  10.1021/jm401530a

文献信息

• Therapeutic compounds
  申请人：Higginbottom Michael

  公开号：US20080076776A1

  公开（公告）日：2008-03-27

  Compounds of formula (I) below are disclosed. Their use as medicaments is described, in particular for the treatment of pain or inflammation: wherein: when X═Y=Z=OH, R 1 is OCH 2 CF 2 CF 3 , phenoxy (substituted with 3-(4-trifluoromethylphenyl), 3,4-dichloro, (3-trifluoromethyl,4-fluoro), (3-trifluoromethyl,4-chloro), (3-chloro, 4-cyano), or 3,5-bis(trifluoromethyl)), 1-piperazinyl(4-(3,4-dichlorophenyl)), phenyl (substituted with 3,4-dichloro, 3,5-difluoro, 3,5-bis(trifluoromethyl) or 3,4,5-trifluoro) or 2-benzofuranyl; or when X═Y═OH and Z=OMe, R 1 is OCH 3 , OCH 2 CHF 2 , OCH 2 cyclopentyl, O-(2,5-difluorophenyl) or (S)-sec-butylamino; or when X═H and Y=Z=OH, R 1 is n-hexylamino or cyclopentylamino; or when (IV) X=Z=OH and Y═H, R 1 is cyclopentylamino; or a pharmaceutically acceptable salt thereof.

  公开了以下式子（I）的化合物。它们的用途作为药物被描述，特别是用于治疗疼痛或炎症：其中：当X═Y=Z=OH，R1为OCH2CF2CF3，苯氧（用3-(4-三氟甲基苯基)、3,4-二氯、(3-三氟甲基，4-氟)、(3-三氟甲基，4-氯)、(3-氯，4-氰基)或3,5-双(三氟甲基)取代的），1-哌嗪基(4-(3,4-二氯苯基))，苯基（用3,4-二氯、3,5-二氟、3,5-双(三氟甲基)或3,4,5-三氟取代的）或2-苯并呋喃基；或当X═Y═OH且Z=OMe，R1为OCH3，OCH2CHF2，OCH2环戊基，O-(2,5-二氟苯基)或(S)-sec-丁基氨基；或当X═H且Y=Z=OH，R1为正己基氨基或环戊基氨基；或当（IV）X=Z=OH且Y═H，R1为环戊基氨基；或其药学上可接受的盐。
• [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
• WO2008/745
  申请人：——

  公开号：——

  公开（公告）日：——
• US7807685B2
  申请人：——

  公开号：US7807685B2

  公开（公告）日：2010-10-05
• Structure–Activity Relationships of Synthetic Cordycepin Analogues as Experimental Therapeutics for African Trypanosomiasis
  作者：Suman K. Vodnala、Thomas Lundbäck、Esther Yeheskieli、Birger Sjöberg、Anna-Lena Gustavsson、Richard Svensson、Gabriela C. Olivera、Anthonius A. Eze、Harry P. de Koning、Lars G. J. Hammarström、Martin E. Rottenberg

  DOI：10.1021/jm401530a

  日期：2013.12.27

  Novel methods for treatment of African trypanosomiasis, caused by infection with Trypanosoma brucei are needed. Cordycepin (3'-deoxyadenosine, la) is a powerful trypanocidal compound in vitro but is ineffective in vivo because of rapid metabolic,degradation by adenosine deaminase (ADA). We elucidated the structural moieties of cordycepin required for trypanocidal activity and designed analogues that retained trypanotoxicity while gaining resistance to ADA-mediated metabolism. 2-Fluorocordycepin (2-fluoro3'-deoxyadenosine, 1b) was identified as a selective, potent, and ADA-resistant trypanocidal compound that cured T. brucei infection in mice. Compound 1b is transported through the high affinity TbAT1/P2 adenosine transporter and is a substrate of T. b. brucei adenosine kinase. 1b has good preclinical properties suitable for an, oral drug, albeit a relatively short plasma half-life. We present a rapid and efficient synthesis of 2-halogenated cordycepins, also useful synthons. for the development of additional novel C2-substituted 3'-deoxyadenosine analogues to be evaluated in development of experimental therapeutics.