9-<<2-hydroxy-1-(hydroxymethyl)ethoxy>methyl>-6-chloro-2-aminopurine | 89419-25-0

• 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-<<2-hydroxy-1-(hydroxymethyl)ethoxy>methyl>-6-chloro-2-aminopurine
• 英文别名: 2-amino-6-chloro-9-(1,3-dihydroxy-2-propoxymethyl)purine；1,3-Propanediol, 2-[(2-amino-6-chloro-9H-purin-9-yl)methoxy]-；2-[(2-amino-6-chloropurin-9-yl)methoxy]propane-1,3-diol
• CAS: 89419-25-0
• 化学式: C₉H₁₂ClN₅O₃
• 分子量: 273.679
• InChiKey: WVIKNNBFRIACOB-UHFFFAOYSA-N

物化性质

• 沸点：
  634.9±65.0 °C(Predicted)
• 密度：
  1.79±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  9-<<2-hydroxy-1-(hydroxymethyl)ethoxy>methyl>-6-chloro-2-aminopurine 在 potassium fluoride 、 三甲胺 作用下， 生成 2-(2-Amino-6-fluoro-purin-9-ylmethoxy)-propane-1,3-diol
  参考文献：
  名称：

  Synthesis and Evaluation of 2-Amino-9-(1,3-dihydroxy-2-propoxymethyl)- 6-fluoropurine Mono- and Diesters as Potential Prodrugs of Ganciclovir

  摘要：

  A series of 2-amino-9-(1,3-dihydroxy-2-propoxymethyl)-6-floropurine mono- and diesters, 6a- h, were synthesized as potential prodrugs of ganciclovir and evaluated for their oral ganciclovir bioavailability in rats. Treatment of 2-amino-6-chloro-9-(1,3-dihydroxy-2-propoxymethyl)purine (4) with Me3N in DMF/THF (1/4) followed by the reaction of the resulting trimethylammonium chloride salt 5 with KF in DMF gave 2-amino-9-( 1,3-dihydroxy-2-propoxymethyl)-6-fluoropurine (2) in 83% yield. Esterification of 2 with an appropriate acid anhydride (Ac2O, (EtCO)(2)O, (n-PrCO)(2)O, or (i-PrCO)(2)O) (6 equiv for 6a-d or 1 equiv for 6e-h) in DMF in the presence of a catalytic amount of DMAP produced the diesters 6a-d in 92-98% yields and the monoesters 6e-h in 37-44% yields. Of the prodrugs tested in rats, the monoisobutyrate 6h achieved the highest ganciclovir bioavailability (45%) that is 15-fold higher than that from ganciclovir (3%), followed in order by the diisobutyrate Sd (42%), the diacetate 6a (41%), the monobutyrate 6g (41%), the monopropionate 6f (39%), the dipropionate 6b (35%), the dibutyrate 6c (35%), and the monoacetate 6e (29%). The prodrugs 6e-h were found to be quite stable at pH 6.0 (t(1/2) = >29 days), 7.4 (t(1/2) =>7 days), and 8.0 (t(1/2) = >2 days) but had relatively short half-lives at pH 1.2 (t(1/2) = 60-83 min).

  DOI：

  10.1021/jm980321+
• 作为产物：
  描述：

  9-[1,3-二(苯基甲氧基)丙-2-基氧基甲基]-6-氯嘌呤-2-胺 在 palladium on activated charcoal 、 氢气 、 sodium acetate 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以95%的产率得到9-<<2-hydroxy-1-(hydroxymethyl)ethoxy>methyl>-6-chloro-2-aminopurine
  参考文献：
  名称：

  Synthesis of a purine acyclonucleoside series having pronounced antiviral activity. The glyceropurines

  摘要：

  描述了一系列嘌呤类似物A*（A-Star，1）的无环核苷化合物的合成。该系列化合物已被证明对疱疹病毒具有显著的活性。这些化合物被命名为“甘油苷”。本报告描述了甘油嘌呤。已构建含有甘油腺嘌呤（A*，化合物1）的核苷酸，这些核苷酸对磷酸二酯酶的降解具有抵抗性。化合物A*既是腺苷脱氨酶的劣质底物，也是劣质抑制剂。

  DOI：

  10.1139/v84-039

文献信息

• Arylsulfonyloxy purine intermediates
  申请人：Merck & Co., Inc.

  公开号：US04897479A1

  公开（公告）日：1990-01-30

  Compounds of the formula ##STR1## and the pharmaceutically acceptable salts thereof are disclosed. In these compounds, R.sup.1 is halogen, --SR.sup.4 wherein R.sup.4 is H or alkyl of 1 to 4 carbon atoms, --OCH.sub.3, --OSO.sub.2 Ar wherein Ar is phenyl or alkyl substituted phenyl wherein the alkyl group has 1 to 6 carbon atoms, --NR.sup.4 R.sup.5 wherein R.sup.4 is as defined above and R.sup.5 is H, alkyl of 1 to 4 carbon atoms, amino, alkanoyl of 1 to 8 carbon atoms, benzoyl, methoxy or hydroxy or R.sup.1 is --N(CH.sub.3).sub.3.sup.+ X.sup.- wherein X is halogen or --OSO.sub.2 Ar wherein Ar is phenyl or alkyl substituted phenyl wherein the alkyl group has 1 to 6 carbon atoms; R.sup.2 is H, alkanoyl of 1 to 8 carbon atoms or benzoyl; R.sup.3 is A or B wherein A is ##STR2## and B is ##STR3## wherein R.sup.6 and R.sup.7 are independently selected from H and ##STR4## wherein R.sup.8 and R.sup.9 are independently selected from pharmaceutically acceptable cations and H, or R.sup.6 and R.sup.7 taken together are ##STR5## wherein R.sup.10 is selected from pharmaceutically acceptable cations and H; with the proviso that R.sup.4 is not H when: R.sup.5 is H, R.sup.3 is A, and R.sup.6 and R.sup.7 are H. The compounds have anti-viral activity.

  本文披露了化学式##STR1##的化合物及其药学上可接受的盐。在这些化合物中，R.sup.1是卤素，-SR.sup.4，其中R.sup.4是H或1至4个碳原子的烷基，-OCH.sub.3，-OSO.sub.2 Ar，其中Ar是苯基或烷基取代的苯基，其中烷基具有1至6个碳原子，-NR.sup.4 R.sup.5，其中R.sup.4如上定义，R.sup.5是H，1至4个碳原子的烷基，氨基，1至8个碳原子的烷酰基，苯甲酰基，甲氧基或羟基，或R.sup.1是-N(CH.sub.3).sub.3.sup.+ X.sup.-，其中X是卤素或-OSO.sub.2 Ar，其中Ar是苯基或烷基取代的苯基，其中烷基具有1至6个碳原子; R.sup.2是H，1至8个碳原子的烷酰基或苯甲酰基; R.sup.3是A或B，其中A是##STR2##，B是##STR3##，其中R.sup.6和R.sup.7分别独立地选择自H和##STR4##，其中R.sup.8和R.sup.9分别独立地选择自药学上可接受的阳离子和H，或R.sup.6和R.sup.7一起选择为##STR5##，其中R.sup.10选择自药学上可接受的阳离子和H; 其中R.sup.5为H，R.sup.3为A，且R.sup.6和R.sup.7为H时，R.sup.4不为H。这些化合物具有抗病毒活性。
• Substituted 9-(1 or 3-monoacyloxy or 1,3-diacyloxy-2-propoxymethyl)purines as antiviral agent
  申请人：SYNTEX (U.S.A.) INC.

  公开号：EP0085424A2

  公开（公告）日：1983-08-10

  Compounds useful as antiviral agents are defined by the following formula: and the acid addition salts, preferably the pharmaceutically acceptable acid addition salt thereof, wherein R1 is hydrogen or -C(O)R7 wherein R7 is hydrogen, alkyl of one to nineteen carbon atoms, hydroxyalkyl of one to eight carbon atoms, alkoxyalkyl of two to nine carbon atoms, alkenyl of two to nineteen carbon atoms, phenyl, 1- adamantyl, 2-carboxyethyl or carboxymethyl and the pharmaceutically acceptable alkali metal salts thereof; R2 is -C(O)R7 wherein R7 is as defined above; R3 is hydrogen, halo, thio, lower alkylthio of one to six carbon atoms, azido, NR9R10 wherein R9 and R10 are independently hydrogen or lower alkyl of one to six carbon atoms or -NHC(O)R8 wherein R8 is hydrogen, alkyl of one to nineteen carbon atoms or 1-adamantyl; and (a) R6 is hydrogen, halo, lower alkoxy of one to six carbon atoms, azido, thio, lower alkythio of one to six carbon atoms, -NR9R10 wherein R9 and R10 are as defined above or -NHC(O)R8 wherein R8 is as defined above and R4 together with R5 is a single bond; or (b) R5 together with R6 is a keto group and R4 is hydrogen.

  可用作抗病毒剂的化合物由下式定义： 及其酸加成盐，最好是药学上可接受的酸加成盐，其中 R1 是氢或-C(O)R7，其中 R7 是氢、1 至 19 个碳原子的烷基、1 至 8 个碳原子的羟烷基、2 至 9 个碳原子的烷氧基烷基、2 至 19 个碳原子的烯基、苯基、1-金刚烷基、2-羧乙基或羧甲基及其药学上可接受的碱金属盐； R2 是-C(O)R7，其中 R7 如上定义； R3 是氢、卤代、硫代、一至六个碳原子的低级烷硫基、叠氮、NR9R10（其中 R9 和 R10 独立地是氢或一至六个碳原子的低级烷基）或-NHC(O)R8（其中 R8 是氢、一至十九个碳原子的烷基或 1-金刚烷基）；以及 (a) R6 为氢、卤素、一至六个碳原子的低级烷氧基、叠氮、硫代、一至六个碳原子的低级烷硫基、-NR9R10（其中 R9 和 R10 如上所定义）或-NHC(O)R8（其中 R8 如上所定义），且 R4 与 R5 一起为单键；或 (b) R5 与 R6 同为酮基，R4 为氢。
• Substituted 9-(1-0- or 3-0-monosubstituted or 1,3-di-0-substituted 1,3 dihydroxy-2-propoxymethyl) purines as antiviral agents
  申请人：SYNTEX (U.S.A.) INC.

  公开号：EP0105135A1

  公开（公告）日：1984-04-11

  Compounds useful as antiviral agents are defined by the following formula: wherein R1 is hydrogen, -C(Y)OR7 or -C(O)NHR7 wherein R7 is alkyl of one to twelve carbon atoms, alkenyl of two to twelve carbon atoms, cyclopentyl, cyclohexyl, phenyl or benzyl; R2 is -C(Y)OR7 or -C(O)NHR7 wherein R7 is as defined above; Y is oxygen or sulfur; R3 is hydrogen, halo, thio, lower alkylthio of one to six carbon atoms, azido, NR9R10 wherein R9 and R10 are independently hydrogen or lower alkyl of one to six carbon atoms or -NHC(O)R8 wherein R8 is hydrogen, alkyl of one to nineteen carbon atoms or 1-adamantyl; and (a) R6 is hydrogen, halo, lower alkoxy of one to six carbon atoms, azido, thio, lower alkylthio of one to six carbon atoms, -NR9R10 wherein R9 and R10 are as defined above or -NHC(O)R8 wherein R8 is as defined above and R4 together with R5 is a bond; or (b) R5 together with R6 is a keto group and R4 is hydrogen.

  可用作抗病毒剂的化合物按下式定义： 其中 R1是氢、-C(Y)OR7或-C(O)NHR7，其中R7是一至十二个碳原子的烷基、二至十二个碳原子的烯基、环戊基、环己基、苯基或苄基； R2 是-C(Y)OR7 或-C(O)NHR7，其中 R7 如上定义； Y 是氧或硫； R3 是氢、卤素、硫代、一至六个碳原子的低级烷硫基、叠氮、NR9R10（其中 R9 和 R10 独立地是氢或一至六个碳原子的低级烷基）或-NHC(O)R8（其中 R8 是氢、一至十九个碳原子的烷基或 1-金刚烷基）；以及 (a) R6 是氢、卤素、1 至 6 个碳原子的低级烷氧基、叠氮、硫代、1 至 6 个碳原子的低级烷硫基、-NR9R10（其中 R9 和 R10 如上所定义）或-NHC(O)R8（其中 R8 如上所定义）且 R4 与 R5 一起是键；或 (b) R5 与 R6 同为酮基，R4 为氢。
• Purine derivatives, their application in anti-viral compositions
  申请人：Merck & Co., Inc.

  公开号：EP0138683A2

  公开（公告）日：1985-04-24

  Compounds of the formula and the pharmaceutically acceptable salts thereof are disclosed. In these compounds, R1 is halogen, -SR4 wherein R4 is H or alkyl of 1 to 4 carbon atoms, - OCH3, - OSO2Ar wherein Ar is phenyl or alkyl substituted phenyl wherein the alkyl group has 1 to 6 carbon atoms, -NR4R5 wherein R4 is as defined above and R5 is H, alkyl of 1 to 4 carbon atoms, amino, alkanoyl of 1 to 8 carbon atoms, benzoyl, methoxy or hydroxy or R1 is - N(CH3)3+ X- wherein X is halogen or -OSO2Ar wherein Ar is phenyl or alkyl substituted phenyl wherein the alkyl group has 1 to 6 carbon atoms; R2 is H, alkanoyl of 1 to 8 carbon atoms or benzoyl; R3 is A or B wherein A is wherein R6 and R7 are independently selected from wherein R6 and R9 are independently selected from pharmaceutically acceptable cations and H, H, or R6 and R7 taken together are wherein R10 is selected from pharmaceutically acceptable cations and H; with the proviso that R4 is not H when: RS is H, R3 is A, and R6 and R7 are H. The compounds have anti-viral activity.

  公开了式 及其药学上可接受的盐类。在这些化合物中，R1 是卤素，-SR4 其中 R4 是 H 或 1 至 4 个碳原子的烷基，-OCH3，-OSO2Ar 其中 Ar 是苯基或烷基取代的苯基，其中烷基有 1 至 6 个碳原子，-NR4R5 其中 R4 如上定义，R5 是 H、1至4个碳原子的烷基、氨基、1至8个碳原子的烷酰基、苯甲酰基、甲氧基或羟基，或者 R1 是-N(CH3)3+ X-，其中 X 是卤素或-OSO2Ar，其中 Ar 是苯基或烷基取代的苯基，其中烷基具有 1 至 6 个碳原子； R2 是 H、1 至 8 个碳原子的烷酰基或苯甲酰基； R3 是 A 或 B，其中 A 是 其中 R6 和 R7 独立选自 其中 R6 和 R9 独立选自药学上可接受的阳离子和 H、H 或 R6 和 R7 合在一起是 其中R10选自药学上可接受的阳离子和H；但R4在下列情况下不是H这些化合物具有抗病毒活性。
• US4556659A
  申请人：——

  公开号：US4556659A

  公开（公告）日：1985-12-03