(3aR,6R,6aR)-6-(hydroxymethyl)-2,2,3a-trimethyldihydro-3aH-[1,3]dioxolo[4,5-c]pyrrol-4(5H)-one compound | 872534-56-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3aR,6R,6aR)-6-(hydroxymethyl)-2,2,3a-trimethyldihydro-3aH-[1,3]dioxolo[4,5-c]pyrrol-4(5H)-one compound
• 英文别名: (3aR,6R,6aR)-6-(hydroxymethyl)-2,2,3a-trimethyl-6,6a-dihydro-5H-[1,3]dioxolo[4,5-c]pyrrol-4-one
• CAS: 872534-56-0
• 化学式: C₉H₁₅NO₄
• 分子量: 201.222
• InChiKey: RFBYKWMEHJTGKZ-HCVRKRLWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3aR,6R,6aR)-6-(hydroxymethyl)-2,2,3a-trimethyldihydro-3aH-[1,3]dioxolo[4,5-c]pyrrol-4(5H)-one compound 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 17.0h， 以64%的产率得到((3aR,4R,6aS)-2,2,6a-trimethyltetrahydro-3aH-[1,3]dioxolo[4,5-c]pyrrol-4-yl)methanol
  参考文献：
  名称：

  从天然糖和氨基酸合成亚氨基糖（2 R，3 R，4 S）-2-（羟甲基）-4-甲基吡咯烷-3,4-二醇的方法

  摘要：

  从核糖和d-丝氨酸开始，通过两种替代途径制备了亚氨基糖化合物3。由d-丝氨酸（3 R，4 R，5 R）-3,4-二羟基-5-（羟甲基）-3-甲基吡咯烷丁-2-酮以五个步骤制备，总收率为50％，将其进一步转化为（2 R，3 R，4 S）-2-（羟甲基）-4-甲基吡咯烷-3,4-二醇分三步进行，总收率为23％。

  DOI：

  10.1016/j.tetlet.2010.11.068
• 作为产物：
  描述：

  (3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methylpyrrolidin-2-one 、 2,2-二甲氧基丙烷 在 对甲苯磺酸 、 sodium sulfate 作用下， 反应 24.0h， 以24%的产率得到(3aR,6R,6aR)-6-(hydroxymethyl)-2,2,3a-trimethyldihydro-3aH-[1,3]dioxolo[4,5-c]pyrrol-4(5H)-one compound
  参考文献：
  名称：

  从天然糖和氨基酸合成亚氨基糖（2 R，3 R，4 S）-2-（羟甲基）-4-甲基吡咯烷-3,4-二醇的方法

  摘要：

  从核糖和d-丝氨酸开始，通过两种替代途径制备了亚氨基糖化合物3。由d-丝氨酸（3 R，4 R，5 R）-3,4-二羟基-5-（羟甲基）-3-甲基吡咯烷丁-2-酮以五个步骤制备，总收率为50％，将其进一步转化为（2 R，3 R，4 S）-2-（羟甲基）-4-甲基吡咯烷-3,4-二醇分三步进行，总收率为23％。

  DOI：

  10.1016/j.tetlet.2010.11.068

文献信息

• [EN] AZA NUCLEOSIDES, PREPARATION THEREOF AND USE AS INHIBITORS OF RNA VIRAL POLYMERASES<br/>[FR] AZANUCLEOSIDES, LEUR PREPARATION ET LEUR UTILISATION COMME INHIBITEUR DES ARN POLYMERASES VIRALES
  申请人：BIOCRYST PHARM INC

  公开号：WO2006002231A1

  公开（公告）日：2006-01-05

  Compounds represented by the formula: (I), and pharmaceutically acceptable salts thereof and prodrugs thereof; wherein Rl is H, CH3, C2H5, C3H7 R2 is H, CH3, C2H5, C3H7, CH=CH2, CH2-OH, CH2F, CF3 R'2 is H, OH, NH2, NH-alkyl, F, N3, OCH3, O-C(O)CH(NH2)alkyl R3 is H, CH3, C2H5, C3H7 R'3 is H, OH, NH2, NH-alkyl, F, N3, OCH3, O-C(O)CH(NH2)alkyl R4 is H, CH3, C2H5, C3H7 At least one of R2, R3, or R4 has to be other than H, when X=NH in B R6 is H, CH3, C2H5, -C-CH3 R7 is selected from H, alkyl, alkenyl, aryl, acyloxyalkyl, and pivaloyloxyalkyl, aminoacids, CH2CH2SC(O)alkyl; and B is represented by the following structure: X is independently NR6, O, S, R8 and R9 independently is H, NH2, OH, SH, F, Cl, Br, I, aryl, heterocycle, alkyl, alkene, alkyne, S-alkyl, S-aryl, S(O)-alkyl, SO2-alkyl, SO2NH2, SO2NH-alkyl, SO2NH-aryl, NH-alkyl, NH-aryl, N(alkyl)2, N(aryl)2, O-alkyl, O-aryl, O-heterocycle, NH-(CH2)n-aryl, NH-C(O)-alkyl, NH-C(O)-aryl are useful for inhibiting viral RNA polymerases and treating patients suffering from diseases caused by various RNA viruses.

  由以下公式表示的化合物：(I)，以及其药用盐和前药；其中R1为H，CH3，C2H5，C3H7；R2为H，CH3，C2H5，C3H7，CH=CH2，CH2-OH，CH2F，CF3；R'2为H，OH，NH2，NH-烷基，F，N3，OCH3，O-C(O)CH(NH2)烷基；R3为H，CH3，C2H5，C3H7；R'3为H，OH，NH2，NH-烷基，F，N3，OCH3，O-C(O)CH(NH2)烷基；R4为H，CH3，C2H5，C3H7；当X=NH时，R2，R3或R4中至少有一个不是H；R6为H，CH3，C2H5，-C-CH3；R7从H，烷基，烯基，芳基，酰氧烷基，皮瓦洛氧烷基，氨基酸，CH2CH2SC(O)烷基中选择；B由以下结构表示：X独立地为NR6，O，S；R8和R9独立地为H，NH2，OH，SH，F，Cl，Br，I，芳基，杂环，烷基，烯烃，炔烃，S-烷基，S-芳基，S(O)-烷基，SO2-烷基，SO2NH2，SO2NH-烷基，SO2NH-芳基，NH-烷基，NH-芳基，N(烷基)2，N(芳基)2，O-烷基，O-芳基，O-杂环，NH-(CH2)n-芳基，NH-C(O)-烷基，NH-C(O)-芳基对抑制病毒RNA聚合酶并治疗由各种RNA病毒引起的疾病的患者具有用处。
• AZA nucleosides, preparation thereof and use as inhibitors of RNA viral polymerases
  申请人：Babu S. Yarlagadda

  公开号：US20070099942A1

  公开（公告）日：2007-05-03

  Compounds represented by the formula: , and pharmaceutically acceptable salts thereof and prodrugs thereof; wherein R 1 is H, CH 3 , C 2 H 5 , C 3 H 7 R 2 is H, CH 3 , C 2 H 5 , C 3 H 7 , CH═CH 2 , CH 2 —OH, CH 2 F, CF 3 R′ 2 is H, OH, NH 2 , NH-alkyl, F, N 3 , OCH 3 , O—C(O)CH(NH 2 )alkyl R 3 is H, CH 3 , C 2 H 5 , C 3 H 7 R′ 3 is H, OH, NH 2 , NH-alkyl, F, N 3 , OCH 3 , O—C(O)CH(NH 2 )alkyl R 4 is H, CH 3 , C 2 H 5 , C 3 H 7 At least one of R 2 , R 3 , or R 4 has to be other than H, when X═NH in B R 6 is H, CH 3 , C 2 H 5 , R 7 is selected from H, alkyl, alkenyl, aryl, acyloxyalkyl, and pivaloyloxyalkyl, aminoacids, CH 2 CH 2 SC(O)alkyl; and B is represented by the following structure: X is independently NR 6 , O, S, R 8 and R 9 independently is H, NH 2 , OH, SH, F, Cl, Br, I, aryl, heterocycle, alkyl, alkene, alkyne, S-alkyl, S-aryl, S(O)-alkyl, SO 2 -alkyl, SO 2 NH 2 , SO 2 NH-alkyl, SO 2 NH-aryl, NH-alkyl, NH-aryl, N(alkyl) 2 , N(aryl) 2 , O-alkyl, O-aryl, O-heterocycle, NH-(CH 2 ) n -aryl, NH—C(O)-alkyl, NH—C(O)-aryl are useful for inhibiting viral RNA polymerases and treating patients suffering from diseases caused by various RNA viruses.

  该化合物的结构式为：其中R1为H，CH3，C2H5，C3H7；R2为H，CH3，C2H5，C3H7，CH═CH2，CH2—OH，CH2F，CF3；R′2为H，OH，NH2，NH-烷基，F，N3，OCH3，O—C（O）CH（NH2）烷基；R3为H，CH3，C2H5，C3H7；R′3为H，OH，NH2，NH-烷基，F，N3，OCH3，O—C（O）CH（NH2）烷基；R4为H，CH3，C2H5，C3H7。当X═NH时，R2、R3或R4中至少有一个不为H。BR6为H，CH3，C2H5；R7选择自H、烷基、烯烃基、芳香基、酰氧烷基和哌酰氧烷基、氨基酸、CH2CH2SC（O）烷基；B的结构式如下：其中X独立为NR6，O，S；R8和R9独立为H，NH2，OH，SH，F，Cl，Br，I，芳香基，杂环，烷基，烯烃基，炔基，S-烷基，S-芳香基，S（O）-烷基，SO2-烷基，SO2NH2，SO2NH-烷基，SO2NH-芳香基，NH-烷基，NH-芳香基，N（烷基）2，N（芳香基）2，O-烷基，O-芳香基，O-杂环，NH-（CH2）n-芳香基，NH—C（O）-烷基，NH—C（O）-芳香基。这些化合物可用于抑制病毒RNA聚合酶和治疗由各种RNA病毒引起的患者。此外，还包括这些化合物的药物可接受的盐和前药。
• ANTIVIRAL AZASUGAR-CONTAINING NUCLEOSIDES
  申请人：BIOCRYST PHARMACEUTICALS, INC.

  公开号：US20150291596A1

  公开（公告）日：2015-10-15

  Disclosed are compounds comprising an azasugar attached to a heterocyclic base, including pharmaceutically acceptable salts thereof, suitable for use in inhibiting viral RNA polymerase activity or viral replication, and treating viral infections. The compounds are characterized, in part, by favorable pharmacokinetics for the active pharmaceutical ingredient, particularly in conjunction with enteral administration, including, in particular, oral administration. Also disclosed are pharmaceutical compositions comprising one or more compounds mentioned above, or pharmaceutically acceptable salts thereof, as well as methods for preparing same. Also provided are methods for inhibiting viral RNA polymerase activity, viral replication, and treating viral infections.

  本发明涉及一种含有偶氮糖与杂环碱基结合的化合物，包括其药学上可接受的盐，适用于抑制病毒RNA聚合酶活性或病毒复制，并用于治疗病毒感染。该化合物的特点之一是具有良好的药代动力学，特别是在肠道给药的情况下，包括口服给药。本发明还涉及含有上述一种或多种化合物或其药学上可接受的盐的制药组合物，以及制备它们的方法。本发明还提供了抑制病毒RNA聚合酶活性、病毒复制和治疗病毒感染的方法。
• US7560434B2
  申请人：——

  公开号：US7560434B2

  公开（公告）日：2009-07-14
• [EN] ANTIVIRAL AZASUGAR-CONTAINING NUCLEOSIDES<br/>[FR] NUCLÉOSIDES ANTIVIRAUX CONTENANT DE L'AZASUCRE
  申请人：BIOCRYST PHARM INC

  公开号：WO2014078778A2

  公开（公告）日：2014-05-22

  Disclosed are compounds comprising an azasugar attached to a heterocyclic base, including pharmaceutically acceptable salts thereof, suitable for use in inhibiting viral RNA polymerase activity or viral replication, and treating viral infections. The compounds are characterized, in part, by favorable pharmacokinetics for the active pharmaceutical ingredient, particularly in conjunction with enteral administration, including, in particular, oral administration. Also disclosed are pharmaceutical compositions comprising one or more compounds mentioned above, or pharmaceutically acceptable salts thereof, as well as methods for preparing same. Also provided are methods for inhibiting viral RNA polymerase activity, viral replication, and treating viral infections.