2,6-anhydro-3,5-dideoxy-5-acrylamido-D-glycero-D-galacto-non-2-enoic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2,6-anhydro-3,5-dideoxy-5-acrylamido-D-glycero-D-galacto-non-2-enoic acid
• 英文别名: (2R,3R,4S)-3-(Acryloylamino)-4-hydroxy-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid；(2R,3R,4S)-4-hydroxy-3-(prop-2-enoylamino)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid
• 化学式: C₁₂H₁₇NO₈
• 分子量: 303.269
• InChiKey: ACESPDVJLWHBJT-FAMUSVHTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  157
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate 在 barium dihydroxide 、 水 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 18.0h， 生成 2,6-anhydro-3,5-dideoxy-5-acrylamido-D-glycero-D-galacto-non-2-enoic acid
  参考文献：
  名称：

  The design, synthesis and biological evaluation of neuraminic acid-based probes of Vibrio cholerae sialidase

  摘要：

  A molecular modelling study using the program GRID has been used to investigate the structural requirements of a potential inhibitor binding to Vibrio cholerae sialidase. A number of favourable interactions were predicted between the sialidase and Neu2en derivatives containing hydroxyl- or halogen-substituted acyl groups on the C-5 amine. As a result of this study, a detailed analysis of the interactions of C-5-substituted Neu2en derivatives with the active site of V. cholerae sialidase was undertaken using a conformational searching routine based on molecular dynamics. Based on the results of these molecular design studies several N-acyl-Neu2en-based probes were prepared and evaluated for sialidase inhibition. As envisaged, and pleasingly, the designed compounds were found to be accommodated by the enzyme's active site architecture, and to be strong inhibitors of V. cholerae sialidase. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(99)00552-2

文献信息

• Compounds useful for inhibiting paramyxovirus neuraminidase
  申请人：——

  公开号：US20030187063A1

  公开（公告）日：2003-10-02

  Compounds represented by the formula: 1 wherein X is selected from the group consisting of: CHR, O, NR, N—OR, NR(O), S, S(O) and S(O)O X 1 is selected from the group consisting of CR, N, and N(O); R is selected from the group consisting of: H, alkyl, alkene, alkyne, CN, NO 2 , N 3 , halo and NHR 10 ; R 1 is selected from the group consisting of: H, (CH 2 )nCO 2 R 10 , (CH 2 )n-tetrazol, (CH 2 )nSO 3 H, (CH 2 )nSO 2 H, (CH 2 )nPO 3 H 2 , (CH 2 )nCONR 10 , (CH 2 )nNO 2 , and (CH 2 )nCHO; R 1a is selected from the group consisting of: H, (CH 2 )nOR 10 , (CH 2 )nCN, (CH 2 )nNR 10 R 10a , (CH 2 )nNHC(O)R 10 , (CH 2 )nC(O)NR 10 R 10a , and (CH 2 )nOC(O)R 10 ; R 1 and R 1a both cannot be H each of R 2 and R 2a is independently selected from the group consisting of H, halo, CN, (CH 2 )nCO 2 R 10 , (CH 2 )nNR 10 R 10a and (CH 2 ) n —OR 10 ; each of R 3 and R 3a is independently selected from the group consisting of: H, NHSO 2 R 10 , N(O)—SO 2 R 10 , NR 10 SO 2 R 10a , (CH 2 )mYR 10 , and (CH 2 )mR 6 ; at least one of R 3 and R 3a should be other than H Y is selected from the group consisting of: O, NH, NHC(O), C(O)NH, S, S(O), S(O)O, NHS(O)O, S(O)ONH, NHC(O)NH and heterocycle; R 3 and R 3a together may be ═O, ═CHR 6 , ═CHR 10 , ═NR 10 , NR 10 and ═N—OR 10 R 4 and R 4a is independently selected from the group consisting of: H, (CH 2 )mYR 10 and (CH 2 )mR 6 R 4 and R 4a together may be: ═O, ═CHR 6 , ═CHR 10 , ═NR 10 and ═N—OR 10 each of R 5 and R 5a is independently selected from the group consisting of C(R 7 )(R 7a ), C(R 7 )(R 7a )C(R 8 )(R 8a ), C(R 7 )(R 7a )C(R 8 )(R 8a )C(R 9 )(R 9a ), OC(R 7 )(R 7a ), OC(R 7 )(R 7a )C(R 8 )(R 8a ), C(R 7 )(R 7a )OC(R 8 )(R 8a ), N(R 10 )C(R 7 )(R 7a ), N(R 10 ) C(R 7 )(R 7a )C(R 8 )(R 8a ), C(R 7 )(R 7a )N(R 10 )C(R 8 )(R 8a ), and C(O)NR 10 R 10a ; R 6 is selected from the group consisting of H, halo, CN, NO 2 , N 3 , CO 2 R 10 , R 10 and NR 10 R 10a ; R 7 , R 7a , R 8 , R 8a , R 9 and R 9a is selected from the group from the group consisting of: H, (CH 2 )mYR 10 and (CH 2 )mR 6 each of the R 10 and R 10a is individually selected from the groups consisting of: H, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heterocycle, substituted heterocycle, alkenyl, substituted alkenyl, alkynyl, and substituted alkynyl; Each of m and n is individually 0, 1, 2, 3, or 4; and pharmaceutically acceptable salt thereof; and prodrugs thereof, and uses thereof.

  该化合物的结构式为：1，其中X从以下组中选择：CHR，O，NR，N—OR，NR（O），S，S（O）和S（O）OX1从以下组中选择：CR，N和N（O）；R从以下组中选择：H，烷基，烯烃，炔烃，CN，NO2，N3，卤素和NHR10；R1从以下组中选择：H，（CH2）nCO2R10，（CH2）n-四唑，（CH2）nSO3H，（CH2）nSO2H，（CH2）nPO3H2，（CH2）nCONR10，（CH2）nNO2和（CH2）nCHO；R1a从以下组中选择：H，（CH2）nOR10，（CH2）nCN，（CH2）nNR10R10a，（CH2）nNHC（O）R10，（CH2）nC（O）NR10R10a和（CH2）nOC（O）R10；R1和R1a都不能是H；R2和R2a各自从H，卤素，CN，（CH2）nCO2R10，（CH2）nNR10R10a和（CH2）n—OR10中选择；R3和R3a各自从H，NHSO2R10，N（O）—SO2R10，NR10SO2R10a，（CH2）mYR10和（CH2）mR6中选择；其中至少有一个R3和R3a不是H，Y从以下组中选择：O，NH，NHC（O），C（O）NH，S，S（O），S（O）O，NHS（O）O，S（O）ONH，NHC（O）NH和杂环；R3和R3a可以组成&boxH；O，&boxH；CHR6，&boxH；CHR10，&boxH；NR10，NR10和&boxH；N—OR10；R4和R4a各自从H，（CH2）mYR10和（CH2）mR6中选择；其中R5和R5a各自从C（R7）（R7a），C（R7）（R7a）C（R8）（R8a），C（R7）（R7a）C（R8）（R8a）C（R9）（R9a），OC（R7）（R7a），OC（R7）（R7a）C（R8）（R8a），C（R7）（R7a）OC（R8）（R8a），N（R10）C（R7）（R7a），N（R10）C（R7）（R7a）C（R8）（R8a），C（R7）（R7a）N（R10）C（R8）（R8a）和C（O）NR10R10a中选择；R6从以下组中选择：H，卤素，CN，NO2，N3，CO2R10，R10和NR10R10a；R7、R7a、R8、R8a、R9和R9a从以下组中选择：H，（CH2）mYR10和（CH2）mR6；R10和R10a各自从以下组中选择：H，烷基，取代烷基，芳基，取代芳基，芳基烷基，取代芳基烷基，杂环，取代杂环，烯基，取代烯基，炔基和取代炔基；m和n各自为0、1、2、3或4；以及其药学上可接受的盐和前药，以及其用途。
• US7045535B2
  申请人：——

  公开号：US7045535B2

  公开（公告）日：2006-05-16
• The design, synthesis and biological evaluation of neuraminic acid-based probes of Vibrio cholerae sialidase
  作者：Jennifer C Wilson、Robin J Thomson、Jeffrey C Dyason、Pas Florio、Kaylene J Quelch、Samia Abo、Mark von Itzstein

  DOI：10.1016/s0957-4166(99)00552-2

  日期：2000.1

  A molecular modelling study using the program GRID has been used to investigate the structural requirements of a potential inhibitor binding to Vibrio cholerae sialidase. A number of favourable interactions were predicted between the sialidase and Neu2en derivatives containing hydroxyl- or halogen-substituted acyl groups on the C-5 amine. As a result of this study, a detailed analysis of the interactions of C-5-substituted Neu2en derivatives with the active site of V. cholerae sialidase was undertaken using a conformational searching routine based on molecular dynamics. Based on the results of these molecular design studies several N-acyl-Neu2en-based probes were prepared and evaluated for sialidase inhibition. As envisaged, and pleasingly, the designed compounds were found to be accommodated by the enzyme's active site architecture, and to be strong inhibitors of V. cholerae sialidase. (C) 2000 Elsevier Science Ltd. All rights reserved.