diethylphospho methyl acetaldehyde dimethyl acetal ether

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: diethylphospho methyl acetaldehyde dimethyl acetal ether
• 英文别名: 2-Diethoxyphosphoryl-1,1-dimethoxypropane;hydrate
• 化学式: C₉H₂₁O₅P*H₂O
• 分子量: 258.252
• InChiKey: SZTJDXKZCQDCFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.44
• 重原子数：
  16
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  55
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-溴-1,1-二甲氧基乙烷 、 羟甲基膦酸二乙酯 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 diethylphospho methyl acetaldehyde dimethyl acetal ether
  参考文献：
  名称：

  Prodrugs phosphorus-containing compounds

  摘要：

  公式I的前药，它们的用途，它们的中间体以及它们的制造方法被描述：

  公开号：

  US06312662B1

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。
• NOVEL PRODRUGS FOR PHOSPHORUS-CONTAINING COMPOUNDS
  申请人：Metabasis Therapeutics, Inc.

  公开号：EP1060182B1

  公开（公告）日：2012-12-19
• US6110903A
  申请人：——

  公开号：US6110903A

  公开（公告）日：2000-08-29
• US6312662B1
  申请人：——

  公开号：US6312662B1

  公开（公告）日：2001-11-06