(4S,5R,6R)-5-acetylamino-6-(dipropylcarbamoyl)-4-(2,2,2-trifluoroacetylmethylamino)-5,6-dihydro-4H-pyran-2-carboxylic acid, benzhydryl ester | 185382-32-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4S,5R,6R)-5-acetylamino-6-(dipropylcarbamoyl)-4-(2,2,2-trifluoroacetylmethylamino)-5,6-dihydro-4H-pyran-2-carboxylic acid, benzhydryl ester
• 英文别名: benzhydryl (2R,3R,4S)-3-acetamido-2-(dipropylcarbamoyl)-4-[methyl-(2,2,2-trifluoroacetyl)amino]-3,4-dihydro-2H-pyran-6-carboxylate
• CAS: 185382-32-5
• 化学式: C₃₁H₃₆F₃N₃O₆
• 分子量: 603.639
• InChiKey: OWLSVTIVTNLWOR-VXQMPNGUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  43
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (4S,5R,6R)-5-acetylamino-6-(dipropylcarbamoyl)-4-(2,2,2-trifluoroacetylmethylamino)-5,6-dihydro-4H-pyran-2-carboxylic acid, benzhydryl ester 在 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 生成 (4S,5R,6R)-5-Acetylamino-6-(dipropylcarbamoyl)-4-methylamino-5,6-dihydro-4H-pyran-2-carboxylic acid, trifluoroacetate salt
  参考文献：
  名称：

  6-Carboxamido dihydropyran derivatives

  摘要：

  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代表一个基团SO.sub.2 R.sup.7或COR.sup.7；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，其中烷基被选择自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环烷基和可选择的取代芳基的一个或多个基团取代；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，芳基或被选择自NR.sup.13 R.sup.14，COR.sup.13，C.sub.3-8环烷基，CN，N.sub.3，OR.sup.13和可选择的取代芳基的一个或多个基团取代的C.sub.1-4烷基；或R.sup.5和R.sup.6一起形成一个C.sub.2-6碳氢链，该链可选择地含有一个NR.sup.13基团，该链可选择地被1、2、3或4个被氧和C.sub.1-6烷基基团选择的基团取代，这些基团可选择地被羟基或可选择的取代芳基取代；R.sup.7代表C.sub.1-6烷基，可选择地被一个或多个卤素原子取代，C.sub.3-8环烷基或可选择的取代芳基；R.sup.8，R.sup.9和R.sup.10分别独立地代表H，C.sub.1-6烷基，氨基，羟基，氰基或硝基；R.sup.11代表D-或L-氨基酸的侧链；R.sup.12代表NR.sup.13 R.sup.14，OR.sup.13或R.sup.13；每个R.sup.13和每个R.sup.14独立地代表H，C.sub.1-6烷基或可选择的取代芳基C.sub.1-4烷基；R.sup.15代表C.sub.1-6烷基；它们的药用可接受衍生物是神经氨酸酶抑制剂，用于治疗病毒感染。

  公开号：

  US05990156A1
• 作为产物：
  描述：

  (4S,5R,6R)-5-Acetylamino-4-amino-6-dipropylcarbamoyl-5,6-dihydro-4H-pyran-2-carboxylic acid benzhydryl ester 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (4S,5R,6R)-5-acetylamino-6-(dipropylcarbamoyl)-4-(2,2,2-trifluoroacetylmethylamino)-5,6-dihydro-4H-pyran-2-carboxylic acid, benzhydryl 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

• 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.
• 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代表一个基团SO.sub.2 R.sup.7或COR.sup.7；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，其中烷基被选择自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环烷基和可选择的取代芳基的一个或多个基团取代；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，芳基或被选择自NR.sup.13 R.sup.14，COR.sup.13，C.sub.3-8环烷基，CN，N.sub.3，OR.sup.13和可选择的取代芳基的一个或多个基团取代的C.sub.1-4烷基；或R.sup.5和R.sup.6一起形成一个C.sub.2-6碳氢链，该链可选择地含有一个NR.sup.13基团，该链可选择地被1、2、3或4个被氧和C.sub.1-6烷基基团选择的基团取代，这些基团可选择地被羟基或可选择的取代芳基取代；R.sup.7代表C.sub.1-6烷基，可选择地被一个或多个卤素原子取代，C.sub.3-8环烷基或可选择的取代芳基；R.sup.8，R.sup.9和R.sup.10分别独立地代表H，C.sub.1-6烷基，氨基，羟基，氰基或硝基；R.sup.11代表D-或L-氨基酸的侧链；R.sup.12代表NR.sup.13 R.sup.14，OR.sup.13或R.sup.13；每个R.sup.13和每个R.sup.14独立地代表H，C.sub.1-6烷基或可选择的取代芳基C.sub.1-4烷基；R.sup.15代表C.sub.1-6烷基；它们的药用可接受衍生物是神经氨酸酶抑制剂，用于治疗病毒感染。