cis-2-hydroxymethyl-4-(2'-amino-6'-cyclopropylamino-purine-9'-yl)-1,3-dioxolane

• 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: cis-2-hydroxymethyl-4-(2'-amino-6'-cyclopropylamino-purine-9'-yl)-1,3-dioxolane
• 英文别名: [(2S,4S)-4-[2-amino-6-(cyclopropylamino)purin-9-yl]-1,3-dioxolan-2-yl]methanol
• 化学式: C₁₂H₁₆N₆O₃
• 分子量: 292.297
• InChiKey: ATSMZGDYBPOXMZ-YUMQZZPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  120
• 氢给体数：
  3
• 氢受体数：
  8

文献信息

• [EN] PHOSPHORAMIDATE NUCLEOSIDE PRODRUG FOR TREATING VIRAL DISEASES AND CANCER, PROCESSES FOR THEIR PREPARATION AND THEIR USE<br/>[FR] PROMÉDICAMENT NUCLÉOSIDE PHOSPHORAMIDATE DESTINÉ AU TRAITEMENT DES MALADIES VIRALES ET DU CANCER, LEURS PROCÉDÉS DE PRÉPARATION ET LEUR UTILISATION
  申请人：IVACHTCHENKO ALEXANDRE VASILIEVICH

  公开号：WO2018022221A1

  公开（公告）日：2018-02-01

  The present invention pertains to chemotherapeutic agents and their use for treating viral and cancerous diseases. These compounds are inhibitors of HCV NS5B polymerase, HBV DNA polymerase and, HIV-1 reverse transcriptase (RT) inhibitor, and for treatment of hepatitis B and C infection in mammals. These compounds are also of interest for the treatment of cancer. The phosphoramidate nucleoside prodrug of the general formula (1), a stereoisomer, isotope-enriched analogue, pharmaceutically acceptable salt, hydrate, solvate, or crystalline or polymorphic form thereof, formula (1) wherein: Ar is aryl or hetaryl; R1 is H or CH3, R2 is the substituent selected from OCH2CH=CH2, OCH2CH≡CH, OCH2CH2CH2OCH3, formula (2), formula (3) or formula (4), R3 is H or CH3; R4 is OH, OR5, NR6R7; R5 is C1-C4-alkyl; R6 and R7 are not necessarily the same substituents selected from H or CH3, Z = O, or NH; an arrow (→) indicates the place of substituent connection; Nuc is formula (5) or (6); R8 and R9 are not necessarily the same substituents selected from H, F, Cl, CH3 or OH provided when continuous line and its accompanying dotted line ( ) together are the single carbon-carbon (C-C) bond or R8 and R9 are hydrogen provided when continuous line and its accompanying dotted line ( ) together are the double carbon-carbon bond (C=C); R10 is the substituent selected from R10.1- R10.5; R10.1 R10.2 R10.4 R10.5 ; R11 is the substituent selected from H, F, CI, CH3, or CF3; R12 is hydrogen, C1-C4-alkyl or C3-C6-cycloalkyl; X is oxygen or ethanediyl-1,1 (C=CH2); Y is O, S, CH2, or HO-CH group provided when continuous line and its accompanying dotted line (formula 7) together are the single carbon-carbon (C-C) bond or Y is CH group provided when continuous line and its accompanying dotted line (formula 7) together are the double carbon-carbon bond (C=C), and compound of the general formula (1), stereoisomers, isotope-enriched analogues, pharmaceutically acceptable salts, hydrates, solvates, or crystalline or polymorphic forms thereof, wherein: Ar is aryl or hetaryl; R1 is H or CH3; R2 is isopropyl; Nuc is formula (8), (9) or (10).

  本发明涉及化疗药物及其用于治疗病毒性和癌症疾病的用途。这些化合物是HCV NS5B聚合酶、HBV DNA聚合酶和HIV-1逆转录酶（RT）抑制剂，用于治疗哺乳动物中的乙型和丙型肝炎感染。这些化合物也对癌症治疗具有兴趣。通用式（1）的磷酰胺核苷前药的立体异构体、同位素富集类似物、药学上可接受的盐、水合物、溶剂合物或晶体或多形式，式（1）其中：Ar为芳基或杂芳基；R1为H或CH3，R2为从OCH2CH=CH2、OCH2CH≡CH、OCH2CH2CH2OCH3、式（2）、式（3）或式（4）中选择的取代基，R3为H或CH3；R4为OH、OR5、NR6R7；R5为C1-C4-烷基；R6和R7不一定相同，选择自H或CH3的取代基，Z=O或NH；箭头（→）表示取代基连接的位置；Nuc为式（5）或（6）；R8和R9不一定相同，选择自H、F、Cl、CH3或OH，提供当连续线及其相应的虚线（）一起为单碳-碳（C-C）键时，或R8和R9为氢，提供当连续线及其相应的虚线（）一起为双碳-碳键（C=C）时；R10为从R10.1-R10.5中选择的取代基；R10.1 R10.2 R10.4 R10.5；R11为从H、F、Cl、CH3或CF3中选择的取代基；R12为氢、C1-C4-烷基或C3-C6-环烷基；X为氧或乙烯二基-1,1（C=CH2）；Y为O、S、CH2或HO-CH基，提供当连续线及其相应的虚线（式7）一起为单碳-碳（C-C）键时，或Y为CH基，提供当连续线及其相应的虚线（式7）一起为双碳-碳键（C=C）时，以及通用式（1）的化合物、立体异构体、同位素富集类似物、药学上可接受的盐、水合物、溶剂合物或晶体或多形式，其中：Ar为芳基或杂芳基；R1为H或CH3；R2为异丙基；Nuc为式（8）、（9）或（10）。
• Antiviral nucleoside analogues
  申请人：BioChem Pharma Inc.

  公开号：US20010049372A1

  公开（公告）日：2001-12-06

  In accordance with the present invention there is provided a nucleoside analogue of formula (I) or (Ia) which is useful as an antiviral agent.

  根据本发明提供了一种式(I)或(Ia)的核苷类似物，可作为抗病毒药物。
• Method for the treatment or prevention of Flaviviridea viral infection using nucleoside analogues
  申请人：BioChem Pharma Inc.

  公开号：US20030225037A1

  公开（公告）日：2003-12-04

  In accordance with the present invention there is provided a method for treating or preventing a Flaviviridea viral infection in a host comprising administering a therapeutically effective amount of at least one compound of formula (I) or (II) 1 or or a pharmaceutically acceptable salts thereof, wherein Ra, R, Z and Y are defined in the application.

  根据本发明，提供了一种用于治疗或预防宿主中的Flavivirideaviral感染的方法，包括给予至少一种式(I)或(II)1或它们的药学上可接受的盐的治疗有效量，其中Ra、R、Z和Y在申请中有定义。
• ANTIVIRAL NUCLEOSIDE ANALOGUES
  申请人：Shire BioChem Inc.

  公开号：EP1140937B1

  公开（公告）日：2003-11-12
• METHOD FOR THE TREATMENT OR PREVENTION OF i FLAVIVIRIDAE /i VIRAL INFECTION USING NUCLEOSIDE ANALOGUES
  申请人：BIOCHEM PHARMA INC

  公开号：EP1225899A2

  公开（公告）日：2002-07-31