6-chloro-5-amino-4-(neopentylamino)-pyrimidine | 213248-52-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 6-chloro-5-amino-4-(neopentylamino)-pyrimidine
• 英文别名: 4-chloro-5-amino-6-neopentylaminopyrimidine；5-amino-6-chloro-4-neopentylaminopyrimidine；6-chloro-5-amino-4-(neopentylamino)pyrimidine；6-chloro-4-N-(2,2-dimethylpropyl)pyrimidine-4,5-diamine
• CAS: 213248-52-3
• 化学式: C₉H₁₅ClN₄
• 分子量: 214.698
• InChiKey: FBXDVHNRIFRFOX-UHFFFAOYSA-N

物化性质

• 沸点：
  349.3±42.0 °C(Predicted)
• 密度：
  1.222±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  63.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-chloro-5-amino-4-(neopentylamino)-pyrimidine 、 乙酰氧基乙酰氯 在 吡啶 作用下， 以 乙醚 为溶剂， 生成 6-chloro-5-acetoxyacetyl-amino-4-neopentylaminopyrimidine
  参考文献：
  名称：

  Purine inhibitors of fructose 1,6-bisphosphatase

  摘要：

  描述了具有以下结构的新型嘌呤化合物及其作为果糖-1,6-二磷酸酶抑制剂的用途。其中A从以下组中选择：—NR82，—NHSO2R3，—OR5，—SR5，卤素，低碳烷基，—CON(R4)2，胍基，酰胍基，—H和全氟烷基；E从以下组中选择：—H，卤素，低硫代烷基，低全氟烷基，低碳烷基，低烯烃基，低炔烃基，低烷氧基，—CN和—NR72；X从以下组中选择：-烷基-NR—，烷基，烯基，炔基，芳基，杂环芳基，-烷基-NR-烷基-，-烷基-O-烷基-，-烷基-S-烷基-，-烷基-S—，脂环烯，杂环脂环，1,1-二卤代烷基，—C(O)-烷基-，—NR—C(O)—NR′—，-烷基-NR—C(O)—，-烷基-C(O)—NR—，—Ar-烷基-和-烷基-Ar—，所有这些都可以是可选的取代基，其中每个R和R′都是独立选择的—H和低碳烷基，每个“烷基”和“芳基”分别是独立选择的烷基或芳基；Y从以下组中选择：—H，烷基，烯基，炔基，芳基，脂环，杂环脂环，芳基烷基，芳氧基烷基，烷氧基烷基，—C(O)R3，—S(O)2R3，—C(O)—OR3，—CONHR3，—NR22和—OR3，除H外都可以是可选的取代基；以及其药学上可接受的前药和盐。

  公开号：

  US06284748B1
• 作为产物：
  描述：

  4,6-二氯-5-氨基嘧啶 、 特戊胺 在 三乙胺 作用下， 以 正丁醇 为溶剂， 生成 6-chloro-5-amino-4-(neopentylamino)-pyrimidine
  参考文献：
  名称：

  嘌呤类似物的有效合成：FeCl 3 -SiO 2促进4,5-二氨基嘧啶与醛的环化反应，生成6,8,9-三取代嘌呤

  摘要：

  通过6-氯-4,5-二氨基嘧啶和FeCl 3 -SiO 2促进的各种醛的环化，可有效合成6,8,9-三取代嘌呤类似物。硅胶上的氯化亚铁（Fe（III））具有脱水剂和氧化剂的双重作用，并且在后处理过程中可以通过过滤方便地除去。

  DOI：

  10.1016/s0040-4039(00)01074-1

文献信息

• Prodrugs phosphorus-containing compounds
  申请人：Metabasis Therapeutics, Inc.

  公开号：US06312662B1

  公开（公告）日：2001-11-06

  Prodrugs of formula I, their uses, their intermediates, and their method of manufacture are described:

  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：
• Fructose-1,6-bisphosphatase Inhibitors. 1. Purine Phosphonic Acids as Novel AMP Mimics
  作者：Qun Dang、Brian S. Brown、Yan Liu、Robert M. Rydzewski、Edward D. Robinson、Paul D. van Poelje、M. Rami Reddy、Mark D. Erion

  DOI：10.1021/jm900078f

  日期：2009.5.14

  Inhibition of FBPase is considered a promising way to reduce hepatic gluconeogenesis and therefore could be a potential approach to treat type 2 diabetes. Herein we report the discovery of a series of purine phosphonic acids as AMP mimics targeting the AMP site of FBPase, which was achieved using a structure-guided drug design approach. These non-nucleotide purine analogues inhibit FBPase in a similar

  抑制FBPase被认为是减少肝脏糖异生的有前途的方法，因此可能是治疗2型糖尿病的潜在方法。本文中，我们报道了一系列嘌呤膦酸的发现，它们是针对FBPase AMP位点的AMP模拟物，这是使用结构指导药物设计方法实现的。这些非核苷酸嘌呤类似物以与AMP相似的方式和相似的效力抑制FBPase。更重要的是，几种嘌呤类似物表现出有效的细胞和体内降糖活性，从而获得了抑制FBPase作为药物发现靶标的概念证明。例如，就FBPase抑制而言，化合物4.11和4.13与AMP等价。此外，化合物4.11 抑制原代大鼠肝细胞中的葡萄糖生成，并显着降低禁食大鼠的血糖水平。
• Novel purine inhibitors of fructose-1,6-bisphosphatase
  申请人：Dang Qun

  公开号：US20050277619A1

  公开（公告）日：2005-12-15

  Novel purine compounds of Formula 1, pharmaceutically acceptable prodrugs and salts thereof, and their use as fructose 1,6-bisphosphatase inhibitors.

  化合物1的新型嘌呤类化合物，其药物可接受的前药和盐，以及它们作为果糖1,6-二磷酸酶抑制剂的用途。
• 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。