2-anilino-6-chloro-9-(4-acetoxybutyl) purine | 161363-27-5

• 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: 2-anilino-6-chloro-9-(4-acetoxybutyl) purine
• 英文别名: 2-anilino-6-chloro-9-(4-acetoxybutyl)-purine；4-(2-Anilino-6-chloro-9H-purin-9-yl)butyl acetate；4-(2-anilino-6-chloropurin-9-yl)butyl acetate
• CAS: 161363-27-5
• 化学式: C₁₇H₁₈ClN₅O₂
• 分子量: 359.815
• InChiKey: NRBDNMCXPOHNPO-UHFFFAOYSA-N

物化性质

• 沸点：
  563.6±60.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  81.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-anilino-6-chloro-9-(4-acetoxybutyl) purine 在 sodium hydroxide 作用下， 反应 2.0h， 以89%的产率得到2-苯胺基-9-(4-羟基丁基)-3H-嘌呤-6-酮
  参考文献：
  名称：

  Synthesis, Properties, and Pharmacokinetic Studies of N2-Phenylguanine Derivatives as Inhibitors of Herpes Simplex Virus Thymidine Kinases

  摘要：

  Two series of selective inhibitors of herpes simplex virus types 1 and 2 (HSV1,2) thymidine kinases (TK) have been developed as potential treatment of recurrent virus infections. Among compounds related to the potent base analog N-2-[m-(trifluoromethyl)phenyl]guanine (mCF(3)PG), none was a more potent inhibitor than mCF(3)PG itself. Compounds related to the nucleoside N-2-phenyl-2'-deoxyguanosine (PhdG), but with alkyl, hydroxyalkyl, and related substituents at the 9-position in place of the glycosyl group of PhdG, retained significant but variable inhibitory potencies against the HSV TKs. The most potent inhibitor of HSV1 TK among 9-substituted derivatives, 9-(4-hydroxybutyl)-N-2-phenylguanine (HBPG), was a competitive inhibitor with respect to the substrate thymidine but was not itself a substrate for the enzyme. Water solubilities and 1-octanol:water partition coefficients for the 9-substituted N-2-phenylguanines were linearly but oppositely related to the sum of hydrophobic fragmental constants (Sigma f) of the 9-substituents. Four of the inhibitors were given as solutions to mice by iv and ip routes, and the time course of their plasma concentrations was determined by HPLC analysis of the parent compounds. HBPG was completely absorbed by the ip route, and the plasma concentration could be prolonged by use of suspension formulations. HBPG is a candidate for animal trials of the ability of TK inhibitors to prevent recurrent herpes virus infections.

  DOI：

  10.1021/jm00001a010
• 作为产物：
  描述：

  6-chloro-N-phenyl-9H-purin-2-amine 、 4-溴丁基乙酸酯 以 chloroform N,N-dimethylformamide 为溶剂， 以, above, giving 2-anilino-6-chloro-9-(4-acetoxybutyl) purine in a 45% yield (from DMF/chloroform), mp 195°-197° C的产率得到2-anilino-6-chloro-9-(4-acetoxybutyl) purine
  参考文献：
  名称：

  Drugs to prevent recurrent herpes virus infections

  摘要：

  本文介绍了N.sup.2-取代烷基鸟嘌呤和N.sup.2-取代苯基鸟嘌呤化合物，可预防复发性单纯疱疹感染。由于它们在体内能抑制单纯疱疹病毒胸腺嘧啶激酶，这些化合物将预防、减少或减轻人类复发性HSV感染的频率和严重程度。N.sup.2-烷基鸟嘌呤化合物的化学式为：##STR1## 其中R.sub.1是正常或支链C.sub.n H.sub.2n+1（其中n为1-12）；R.sub.2是H、2-去氧核糖呋喃基、（CH.sub.2）.sub.n OH（其中n为2-5）、CH.sub.2 CH（OH）CH.sub.2 OH、（CH.sub.2）.sub.n --COOH（其中n为1-4）、CH.sub.2 CH（OH）CH.sub.2 --O--COR.sub.4、（CH.sub.2）.sub.n --O--COR.sub.4（其中n为2-5）或（CH.sub.2）.sub.n CO--OR.sub.4（其中n为1-4）；R.sub.4是CH.sub.3、CH.sub.2 CH.sub.3、CH.sub.2 CH.sub.2 NH.sub.2、CH.sub.2 CH.sub.2 N（C.sub.2 H.sub.5）.sub.2或CH.sub.2 CH.sub.2 CO.sub.2 H；而R.sub.3是OH、H、Cl或NH.sub.2，或其互变异构体或药学上可接受的盐。N.sup.2-取代苯基鸟嘌呤化合物的结构类似，其中R.sub.1是苯基或在3和4位取代有H、疏水或电子提取基团或CH.sub.2 CH.sub.3的苯基。

  公开号：

  US05646155A1

文献信息

• DRUGS TO PREVENT RECURRENT HERPES VIRUS INFECTIONS
  申请人：UNIVERSITY OF MASSACHUSETTS MEDICAL CENTER

  公开号：EP0794781A1

  公开（公告）日：1997-09-17
• EP0794781A4
  申请人：——

  公开号：EP0794781A4

  公开（公告）日：1998-04-22
• US5646155A
  申请人：——

  公开号：US5646155A

  公开（公告）日：1997-07-08
• [EN] DRUGS TO PREVENT RECURRENT HERPES VIRUS INFECTIONS<br/>[FR] MEDICAMENTS DE PREVENTION CONTRE DES INFECTIONS RECURRENTES PAR LE VIRUS DE L'HERPES
  申请人：UNIVERSITY OF MASSACHUSETTS MEDICAL CENTER

  公开号：WO1996020711A1

  公开（公告）日：1996-07-11

  (EN) N2-substituted alkylguanines and N2-substituted phenylguanine compounds which prevent recurrent herpes simplex infections are disclosed. By virtue of their ability to inhibit herpes virus thymidine kinase $i(in vivo), such compounds will prevent, reduce the frequency of, or reduce the severity of recurrent HSV infections in humans.(FR) L'invention concerne des composés d'alkylguanine N2-substituée et de phénylguanine N2-substituée servant à empêcher des infections récurrentes d'herpès simplex. Etant donné leur capacité d'inhibition de la thymidine kinase du virus de l'herpès $i(in vivo), ces composés serviront à empêcher les infections récurrentes par le virus de l'herpès simplex chez l'homme, ou à diminuer leur fréquence et leur gravité.
• Synthesis, Properties, and Pharmacokinetic Studies of N2-Phenylguanine Derivatives as Inhibitors of Herpes Simplex Virus Thymidine Kinases
  作者：Hongyan Xu、Giovanni Maga、Federico Focher、Emil R. Smith、Silvio Spadari、Joseph Gambino、George E. Wright

  DOI：10.1021/jm00001a010

  日期：1995.1

  Two series of selective inhibitors of herpes simplex virus types 1 and 2 (HSV1,2) thymidine kinases (TK) have been developed as potential treatment of recurrent virus infections. Among compounds related to the potent base analog N-2-[m-(trifluoromethyl)phenyl]guanine (mCF(3)PG), none was a more potent inhibitor than mCF(3)PG itself. Compounds related to the nucleoside N-2-phenyl-2'-deoxyguanosine (PhdG), but with alkyl, hydroxyalkyl, and related substituents at the 9-position in place of the glycosyl group of PhdG, retained significant but variable inhibitory potencies against the HSV TKs. The most potent inhibitor of HSV1 TK among 9-substituted derivatives, 9-(4-hydroxybutyl)-N-2-phenylguanine (HBPG), was a competitive inhibitor with respect to the substrate thymidine but was not itself a substrate for the enzyme. Water solubilities and 1-octanol:water partition coefficients for the 9-substituted N-2-phenylguanines were linearly but oppositely related to the sum of hydrophobic fragmental constants (Sigma f) of the 9-substituents. Four of the inhibitors were given as solutions to mice by iv and ip routes, and the time course of their plasma concentrations was determined by HPLC analysis of the parent compounds. HBPG was completely absorbed by the ip route, and the plasma concentration could be prolonged by use of suspension formulations. HBPG is a candidate for animal trials of the ability of TK inhibitors to prevent recurrent herpes virus infections.