9-(3,3-dimethyl-5-phosphonopentyl)guanine | 155270-69-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 9-(3,3-dimethyl-5-phosphonopentyl)guanine
• 英文别名: 9-(3,3-Dimethyl-5-phosphonopentyl)guanine；[5-(2-amino-6-oxo-1H-purin-9-yl)-3,3-dimethylpentyl]phosphonic acid
• CAS: 155270-69-2
• 化学式: C₁₂H₂₀N₅O₄P
• 分子量: 329.296
• InChiKey: UYGTVQNSPBEEPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  143
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氨基-6-氯嘌呤 在 sodium hydroxide 、 三甲基溴硅烷 、 水 、 potassium carbonate 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 44.0h， 生成 9-(3,3-dimethyl-5-phosphonopentyl)guanine
  参考文献：
  名称：

  Guida; Elliott; Thomas, Journal of Medicinal Chemistry, 1994, vol. 37, # 8, p. 1109 - 1114

  摘要：

  DOI：

文献信息

• Novel prodrugs for phosphorus-containing compounds
  申请人：——

  公开号：US20020052345A1

  公开（公告）日：2002-05-02

  Prodrugs of formula I, their uses, their intermediates, and their method of manufacture are described: 1 wherein: V, W, and W′ are independently selected from the group consisting of —H, alkyl, aralkyl, alicyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, and 1-alkynyl; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group containing 5-7 atoms, optionally 1 heteroatom, substituted with hydroxy, acyloxy, alkoxycarbonyloxy, or aryloxycarbonyloxy attached to a carbon atom that is three atoms from both O groups attached to the phosphorus; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the O attached to the phosphorus; together V and W are connected via an additional 3 carbon atoms to form an optionally substituted cyclic group containing 6 carbon atoms and substituted with one substituent selected from the group consisting of hydroxy, acyloxy, alkoxycarbonyloxy, alkylthiocarbonyloxy, and aryloxycarbonyloxy, attached to one of said carbon atoms that is three atoms from an O attached to the phosphorus; together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl; together W and W′ are connected via an additional 2-5 atoms to form a cyclic group, optionally containing 0-2 heteroatoms, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl; Z is selected from the group consisting of —CHR 2 OH, —CHR 2 OC(O)R 3 , —CHR 2 OC(S)R 3 , —CHR 2 OC(S)OR 3 , —CHR 2 OC(O)SR 3 , —CHR 2 OCO 2 R 3 , —OR 2 , —SR 2 , —CHR 2 N 3 , —CH 2 aryl, —CH(aryl)OH, —CH(CH═CR 2 2)OH, —CH(C≡CR 2 )OH, —R 2 , —NR 2 2 , —OCOR 3 , —OCO 2 R 3 , —SCOR 3 , —SCO 2 R 3 , —NHCOR 2 , —NHCO 2 R 3 , —CH 2 NHaryl, —(CH 2 ) p — OR 12 , and —(CH 2 ) p —SR 12 ; p is an integer 2 or 3; with the provisos that: a) V, Z, W, W′ are not all —H; and b) when Z is —R 2 , then at least one of V, W, and W′ is not —H, alkyl, aralkyl, or alicyclic; R 2 is selected from the group consisting of R 3 and —H; R 3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl; R 12 is selected from the group consisting of —H, and lower acyl; M is selected from the group that attached to PO 3 2− , P 2 O 6 3− , or P 3 O 9 4− is a biologically active agent, and is attached to the phosphorus in formula I via a carbon, oxygen, sulfur or nitrogen atom; and pharmaceutically acceptable prodrugs and salts thereof.

  本文描述了式I的前药、其用途、其中间体及其制备方法：其中：V、W和W′独立地选自由—H、烷基、芳基烷基、脂环烷基、芳香族、取代芳基、杂芳基、取代杂芳基、1-烯基和1-炔基组成的群体；或者V和Z通过额外的3-5个原子连接形成含有5-7个原子的环状基团，可选地含有1个杂原子，取代为羟基、酰氧基、烷氧羰氧基或芳氧羰氧基，连接到距离磷的两个O基团都有3个原子的碳原子上；或者V和Z通过额外的3-5个原子连接形成一个环状基团，可选地含有1个杂原子，融合到与连接到磷的O的β和γ位的芳基团上；或者V和W通过额外的3个碳原子连接形成一个可选地取代的含有6个碳原子的环状基团，并取代有来自羟基、酰氧基、烷氧羰氧基、烷基硫酰氧基和芳基羰氧基的一种取代基，连接到距离磷的一个O上的碳原子上；或者Z和W通过额外的3-5个原子连接形成一个环状基团，可选地含有一个杂原子，且V必须是芳基、取代芳基、杂芳基或取代杂芳基；或者W和W′通过额外的2-5个原子连接形成一个环状基团，可选地含有0-2个杂原子，且V必须是芳基、取代芳基、杂芳基或取代杂芳基；Z选自由—CHR2OH、—CHR2OC（O）R3、—CHR2OC（S）R3、—CHR2OC（S）OR3、—CHR2OC（O）SR3、—CHR2OCO2R3、—OR2、—SR2、—CHR2N3、—CH2芳基、—CH（芳基）OH、—CH（CH═CR22）OH、—CH（C≡CR2）OH、—R2、—NR22、—OCOR3、—OCO2R3、—SCOR3、—SCO2R3、—NHCOR2、—NHCO2R3、—CH2NH芳基、—（CH2）p—OR12和—（CH2）p—SR12；p是整数2或3；具有以下限制条件：a）V、Z、W、W′不全为—H；b）当Z为—R2时，至少有一个V、W或W′不为—H、烷基、芳基烷基或脂环烷基；R2选自由R3和—H组成的群体；R3选自由烷基、芳基、脂环烷基和芳基烷基组成的群体；R12选自由—H和较低酰基组成的群体；M选自连接到PO32−、P2O63−或P3O94−的群体中的生物活性剂，并通过碳、氧、硫或氮原子连接到式I中的磷；以及其药学上可接受的前药和盐。
• Novel-prodrugs for phosphorus-containing compounds
  申请人：Erion D. Mark

  公开号：US20050288240A1

  公开（公告）日：2005-12-29

  Prodrugs of formula I, their uses, their intermediates, and their method of manufacture are described: wherein: V, W, and W′ are independently selected from the group consisting of —H, alkyl, aralkyl, alicyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, and 1-alkynyl; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group containing 5-7 atoms, optionally 1 heteroatom, substituted with hydroxy, acyloxy, alkoxycarbonyloxy, or aryloxycarbonyloxy attached to a carbon atom that is three atoms from both O groups attached to the phosphorus; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the O attached to the phosphorus; together V and W are connected via an additional 3 carbon atoms to form an optionally substituted cyclic group containing 6 carbon atoms and substituted with one substituent selected from the group consisting of hydroxy, acyloxy, alkoxycarbonyloxy, alkylthiocarbonyloxy, and aryloxycarbonyloxy, attached to one of said carbon atoms that is three atoms from an O attached to the phosphorus; together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl; together W and W′ are connected via an additional 2-5 atoms to form a cyclic group, optionally containing 0-2 heteroatoms, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl; Z is selected from the group consisting of —CHR 2 OH, —CHR 2 OC(O)R 3 , —CHR 2 OC(S)R 3 , —CHR 2 OC(S)OR 3 , —CHR 2 OC(O)SR 3 , —CHR 2 OCO 2 R 3 , —OR 2 , —SR 2 , —CHR 2 N 3 , —CH 2 aryl, —CH(aryl)OH, —CH(CH═CR 2 2)OH, —CH(C≡CR 2 )OH, —R 2 , —NR 2 2 , —OCOR 3 , —OCO 2 R 3 , —SCOR 3 , —SCO 2 R 3 , —NHCOR 2 , —NHCO 2 R 3 , —CH 2 NHaryl, —(CH 2 ) p —OR 12 , and —(CH 2 ) p —SR 12 ; p is an integer 2 or 3; with the provisos that: a) V, Z, W, W′ are not all —H; and b) when Z is —R 2 , then at least one of V, W, and W′ is not —H, alkyl, aralkyl, or alicyclic; R 2 is selected from the group consisting of R 3 and —H; R 3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl; R 12 is selected from the group consisting of —H, and lower acyl; M is selected from the group that attached to PO 3 2− , P 2 O 6 3− , or P 3 O 9 4− is a biologically active agent, and is attached to the phosphorus in formula I via a carbon, oxygen, sulfur or nitrogen atom; and pharmaceutically acceptable prodrugs and salts thereof.

  本文描述了公式I的前药、其用途、其中间体以及其制造方法：其中：V、W和W′独立地选自由-H、烷基、芳基烷基、脂环烷基、取代芳基、杂芳基、取代杂芳基、1-烯基和1-炔基组成的群；或者V和Z通过额外的3-5个原子连接形成含有5-7个原子的环状基团，可选地含有1个杂原子，取代羟基、酰氧基、烷氧羰氧基或芳氧羰氧基，连接到离磷的两个O基团都相隔三个原子的碳原子上；或者V和Z通过额外的3-5个原子连接形成一个环状基团，可选地含有1个杂原子，与连接到磷的O的β和γ位的芳基团融合；V和W通过额外的3个碳原子连接形成一个可选地取代的含有6个碳原子的环状基团，取代基选自羟基、酰氧基、烷氧羰氧基、烷基硫酰氧基和芳基羰氧基，连接到离一个连接到磷的O的三个原子的碳原子上；Z和W通过额外的3-5个原子连接形成一个环状基团，可选地含有一个杂原子，V必须是芳基、取代芳基、杂芳基或取代杂芳基；W和W′通过额外的2-5个原子连接形成一个环状基团，可选地含有0-2个杂原子，V必须是芳基、取代芳基、杂芳基或取代杂芳基；Z选自由CHR2OH、CHR2OC(O)R3、CHR2OC(S)R3、CHR2OC(S)OR3、CHR2OC(O)SR3、CHR2OCO2R3、OR2、SR2、CHR2N3、CH2芳基、CH(芳基)OH、CH(CH═CR22)OH、CH(C≡CR2)OH、R2、NR22、OCOR3、OCO2R3、SCOR3、SCO2R3、NHCOR2、NHCO2R3、CH2NH芳基、(CH2)pOR12和(CH2)pSR12；p是整数2或3；但需要满足以下条件：a）V、Z、W、W′不全为—H；并且b）当Z为—R2时，V、W和W′中至少有一个不是—H、烷基、芳基烷基或脂环烷基；R2选自R3和—H的群；R3选自烷基、芳基、脂环烷基和芳基烷基的群；R12选自—H和较低的酰基的群；M选自附着在PO32−、P2O63−或P3O94−上的生物活性剂，并通过碳、氧、硫或氮原子与公式I中的磷相连接；以及其药学上可接受的前药和盐。
• Anti-inflammatory phosphonate compounds
  申请人：Cannizzaro Carina

  公开号：US20060199788A1

  公开（公告）日：2006-09-07

  The invention is related to phosphorus substituted anti-inflammatory compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

  该发明涉及磷取代的抗炎化合物、含有这些化合物的组合物、包括这些化合物的给药治疗方法，以及用于制备这些化合物的过程和中间体。
• PHOSPHONATE COMPOUNDS HAVING IMMUNO-MODULATORY ACTIVITY
  申请人：Cannizzaro Carina

  公开号：US20090227543A1

  公开（公告）日：2009-09-10

  The invention is related to phosphonate substituted compounds having immuno-modulatory activity, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

  本发明涉及磷酸酯取代化合物，具有免疫调节活性，含有这种化合物的组合物，以及包括这种化合物的给药的治疗方法，还涉及用于制备这种化合物的有用过程和中间体。
• Novel phosphorus-containing prodrugs
  申请人：Erion D. Mark

  公开号：US20070249564A1

  公开（公告）日：2007-10-25

  Novel cyclic phosphoramidate prodrugs of drugs of formula I their use in delivery of drugs to the liver, their use in enhancing oral bioavailability, and their method of preparation are described.

  本文介绍了式I药物的新型环状磷酰胺酰化预药，其在药物传递到肝脏方面的应用、增强口服生物利用度方面的应用以及其制备方法。