(4S,5R,6R)-4-azido-6-(dipropylcarbamoyl)-5-(2,2,2-trifluoroacetylamino)-5,6-dihydro-4H-pyran-2-carboxylic acid, methyl ester | 185382-36-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: (4S,5R,6R)-4-azido-6-(dipropylcarbamoyl)-5-(2,2,2-trifluoroacetylamino)-5,6-dihydro-4H-pyran-2-carboxylic acid, methyl ester
• 英文别名: methyl (2R,3R,4S)-4-azido-2-(dipropylcarbamoyl)-3-[(2,2,2-trifluoroacetyl)amino]-3,4-dihydro-2H-pyran-6-carboxylate
• CAS: 185382-36-9
• 化学式: C₁₆H₂₂F₃N₅O₅
• 分子量: 421.376
• InChiKey: HKGVLKNBZIIWPA-MVWJERBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  99.3
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (4S,5R,6R)-4-azido-6-(dipropylcarbamoyl)-5-(2,2,2-trifluoroacetylamino)-5,6-dihydro-4H-pyran-2-carboxylic acid, methyl ester 在 水 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 (4S,5R,6R)-4-Amino-6-(dipropylcarbamoyl)-5-(2,2,2-trifluoroacetylamino)-5,6-dihydro-4H-pyran-2-carboxylic acid
  参考文献：
  名称：

  Sialidase inhibitors related to zanamivir. Further SAR studies of 4-amino-4H-pyran-2-carboxylic acid-6-propylamides

  摘要：

  SAR investigations of the 4- and 5-positions of a series of 4-amino-4H-pyran-2-carboxylic acid 6-carboxamides are reported. Potent inhibitors of influenza A sialidase with marked selectivity over the influenza B enzyme were obtained when the basic 4-amino substituent was replaced by hydroxyl or even deleted. Modifications at the 5-position exhibited a tight steric requirement, with trifluoroacetamide being optimal. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00019-1
• 作为产物：
  描述：

  (2R,3R,4S)-4-Azido-3-(tert-butoxycarbonylamino)-3,4-dihydro-2H-pyran-2,6-dicarboxylic acid 6-methyl ester 在 吡啶 、 盐酸 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 生成 (4S,5R,6R)-4-azido-6-(dipropylcarbamoyl)-5-(2,2,2-trifluoroacetylamino)-5,6-dihydro-4H-pyran-2-carboxylic acid, methyl ester
  参考文献：
  名称：

  Sialidase inhibitors related to zanamivir. Further SAR studies of 4-amino-4H-pyran-2-carboxylic acid-6-propylamides

  摘要：

  SAR investigations of the 4- and 5-positions of a series of 4-amino-4H-pyran-2-carboxylic acid 6-carboxamides are reported. Potent inhibitors of influenza A sialidase with marked selectivity over the influenza B enzyme were obtained when the basic 4-amino substituent was replaced by hydroxyl or even deleted. Modifications at the 5-position exhibited a tight steric requirement, with trifluoroacetamide being optimal. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00019-1

文献信息

• 6-Carboxamido dihydropyran derivatives
  申请人：Biota Scientific Management PTY Ltd.

  公开号：US05990156A1

  公开（公告）日：1999-11-23

  Compounds of formula (I), ##STR1## wherein R.sup.1 represents OR.sup.5, SR.sup.5, NR.sup.5 R.sup.6, N(OR.sup.5)R.sup.6 or N(NR.sup.5 R.sup.6)R.sup.6 ; X represents OH, N.sub.3, NR.sup.3 R.sup.4 or NR.sup.4 CO.sub.2 R.sup.15 ; Y represents H or NHR.sup.2 ; R.sup.2 represents a group SO.sub.2 R.sup.7 or COR.sup.7 ; R.sup.3 represents H, C.sub.1-6 alkyl or C(.dbd.NR.sup.8)NR.sup.9 R.sup.10 ; R.sup.4 represents H or C.sub.1-6 alkyl; R.sup.5 represents H, C.sub.1-20 alkyl, C.sub.3-8 cycloalkyl, C.sub.2-20 alkenyl, C.sub.2-20 alkynyl, CHR.sup.11 COR.sup.12 or C.sub.1-20 alkyl substituted by one or more groups selected from NR.sup.13 R.sup.14, NR.sup.13 COR.sup.14, CO.sub.2 R.sup.13, OR.sup.13, C.sub.3-8 cycloalkyl and optionally substituted aryl; each R.sup.6 independently represents H, C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.2-6 alkenyl, C.sub.2-20 alkynyl, aryl or C.sub.1-4 alkyl substituted by one or more groups selected from NR.sup.13 R.sup.14, COR.sup.13, C.sub.3-8 cycloalkyl, CN, N.sub.3, OR.sup.13 and optionally substituted aryl; or R.sup.5 and R.sup.6 together form a C.sub.2-6 hydrocarbon chain which may optionally contain a group NR.sup.13 which chain is optionally substituted by 1, 2, 3 or 4 groups selected from oxo and C.sub.1-6 alkyl groups which groups may optionally be substituted by hydroxy or optionally substituted aryl; R.sup.7 represents C.sub.1-6 alkyl optionally substituted by one or more halogen atoms, C.sub.3-8 cycloalkyl or optionally substituted aryl; R.sup.8, R.sup.9 and R.sup.10 each independently represent H, C.sub.1-6 alkyl, amino, hydroxy, cyano or nitro; R.sup.11 represents the side chain of a D- or L-amino acid; R.sup.12 represents NR.sup.13 R.sup.14, OR.sup.13 or R.sup.13 ; each R.sup.13 and each R.sup.14 independently represents H, C.sub.1-6 alkyl or optionally substituted arylC.sub.1-4 alkyl; R.sup.15 represents C.sub.1-6 alkyl; and their pharmaceutically acceptable derivatives are neuraminidase inhibitors useful in the treatment of viral infections.

  式(I)的化合物，其中R.sup.1代表OR.sup.5，SR.sup.5，NR.sup.5 R.sup.6，N(OR.sup.5)R.sup.6或N(NR.sup.5 R.sup.6)R.sup.6; X代表OH，N.sub.3，NR.sup.3 R.sup.4或NR.sup.4 CO.sub.2 R.sup.15; Y代表H或NHR.sup.2; R.sup.2代表SO.sub.2 R.sup.7或COR.sup.7基团; R.sup.3代表H，C.sub.1-6烷基或C(.dbd.NR.sup.8)NR.sup.9 R.sup.10; R.sup.4代表H或C.sub.1-6烷基; R.sup.5代表H，C.sub.1-20烷基，C.sub.3-8环烷基，C.sub.2-20烯基，C.sub.2-20炔基，CHR.sup.11 COR.sup.12或C.sub.1-20烷基，其上取代着一个或多个选自NR.sup.13 R.sup.14，NR.sup.13 COR.sup.14，CO.sub.2 R.sup.13，OR.sup.13，C.sub.3-8环烷基和可选取代的芳基的基团; 每个R.sup.6独立地代表H，C.sub.1-6烷基，C.sub.3-8环烷基，C.sub.2-6烯基，C.sub.2-20炔基，芳基或C.sub.1-4烷基，其上取代着一个或多个选自NR.sup.13 R.sup.14，COR.sup.13，C.sub.3-8环烷基，CN，N.sub.3，OR.sup.13和可选取代的芳基的基团; 或R.sup.5和R.sup.6共同形成一个C.sub.2-6烃链，该链可以选择性地含有一个NR.sup.13基团，该链可以取代1、2、3或4个选自氧代和C.sub.1-6烷基基团的基团，这些基团可以选择性地被羟基或可选取代的芳基取代; R.sup.7代表C.sub.1-6烷基，其上可以选择性地取代一个或多个卤素原子，C.sub.3-8环烷基或可选取代的芳基; R.sup.8，R.sup.9和R.sup.10各自独立地表示H，C.sub.1-6烷基，氨基，羟基，氰基或硝基; R.sup.11表示D-或L-氨基酸的侧链; R.sup.12表示NR.sup.13 R.sup.14，OR.sup.13或R.sup.13; 每个R.sup.13和每个R.sup.14独立地表示H，C.sub.1-6烷基或可选取代的芳基C.sub.1-4烷基; R.sup.15表示C.sub.1-6烷基; 它们的药学上可接受的衍生物是神经氨酸酶抑制剂，用于治疗病毒感染。
• Sialidase inhibitors related to zanamivir. Further SAR studies of 4-amino-4H-pyran-2-carboxylic acid-6-propylamides
  作者：Paul G Wyatt、Barry A Coomber、Derek N Evans、Torquil I Jack、Heather E Fulton、Alan J Wonacott、Peter Colman、Jose Varghese

  DOI：10.1016/s0960-894x(01)00019-1

  日期：2001.3

  SAR investigations of the 4- and 5-positions of a series of 4-amino-4H-pyran-2-carboxylic acid 6-carboxamides are reported. Potent inhibitors of influenza A sialidase with marked selectivity over the influenza B enzyme were obtained when the basic 4-amino substituent was replaced by hydroxyl or even deleted. Modifications at the 5-position exhibited a tight steric requirement, with trifluoroacetamide being optimal. (C) 2001 Elsevier Science Ltd. All rights reserved.