(4R,5R,6R)-5-Acetylamino-4-hydroxy-6-(phenethylpropylcarbamoyl)-5,6-dihydro-4H-pyran-2-carboxylic acid | 185381-81-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: (4R,5R,6R)-5-Acetylamino-4-hydroxy-6-(phenethylpropylcarbamoyl)-5,6-dihydro-4H-pyran-2-carboxylic acid
• 英文别名: (2R,3R,4R)-3-acetamido-4-hydroxy-2-[phenethyl(propyl)carbamoyl]-3,4-dihydro-2H-pyran-6-carboxylic acid；(2R,3R,4R)-3-acetamido-4-hydroxy-2-[2-phenylethyl(propyl)carbamoyl]-3,4-dihydro-2H-pyran-6-carboxylic acid
• CAS: 185381-81-1
• 化学式: C₂₀H₂₆N₂O₆
• 分子量: 390.436
• InChiKey: BBDDLPOYPXNOTL-KBAYOESNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  116
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4R,5R,6R)-5-Acetylamino-4-hydroxy-6-(phenethylpropylcarbamoyl)-5,6-dihydro-4H-pyran-2-carboxylic acid 在 吡啶 、 sodium tetrahydroborate 、 四(三苯基膦)钯 作用下， 以 四氢呋喃 为溶剂， 生成 (5R,6R)-5-Acetylamino-6-(phenethyl-propyl-carbamoyl)-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
• 作为产物：
  描述：

  (2-苯乙基)丙胺 在 四丁基氟化铵 、 水 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 (4R,5R,6R)-5-Acetylamino-4-hydroxy-6-(phenethylpropylcarbamoyl)-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

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。
• [EN] 6-CARBOXAMIDO DIHYDROPYRAN DERIVATIVES<br/>[FR] DERIVES DU 6-CARBOXAMIDODIHYDROPYRANE
  申请人：BIOTA SCIENTIFIC MANAGEMENT PTY. LTD.

  公开号：WO1996036628A1

  公开（公告）日：1996-11-21

  (EN) Compounds of formula (I), wherein R1 represents OR5, SR5, NR5R6, N(OR5)R6 or N(NR5R6)R6; X represents OH, N3, NR3R4 or NR4CO2R15; Y represents H or NHR2; R2 represents a group SO2R7 or COR7; R3 represents H, C1-6alkyl or C(=NR8)NR9R10; R4 represents H or C1-6alkyl; R5 represents H, C1-20alkyl, C3-8cycloalkyl, C2-20alkenyl, C2-20alkynyl, CHR11COR12 or C1-20alkyl substituted by one or more groups selected from NR13R14, NR13COR14, CO2R13, OR13, C3-8cycloalkyl and optionally substituted aryl; each R6 independently represents H, C1-6alkyl, C3-8cycloalkyl, C2-6alkenyl, C2-20alkynyl, aryl or C1-4alkyl substituted by one or more groups selected from NR13R14, COR13, C3-8cycloalkyl, CN, N3, OR13 and optionally substituted aryl; or R5 and R6 together form a C2-6 hydrocarbon chain which may optionally contain a group NR13 which chain is optionally substituted by 1, 2, 3 or 4 groups selected from oxo and C1-6alkyl groups which groups may optionally be substituted by hydroxy or optionally substituted aryl; R7 represents C1-6alkyl optionally substituted by one or more halogen atoms, C3-8cycloalkyl or optionally substituted aryl; R8, R9 and R10 each independently represent H, C1-6alkyl, amino, hydroxy, cyano or nitro; R11 represents the side chain of a D- or L-amino acid; R12 represents NR13R14, OR13 or R13; each R13 and each R14 independently represents H, C1-6alkyl or optionally substituted arylC1-4alkyl; R15 represents C1-6alkyl; and their pharmaceutically acceptable derivatives are neuraminidase inhibitors useful in the treatment of viral infections.(FR) L'invention porte sur des composés de formule (I) dans laquelle: R1 représente OR5, SR5, NR5R6, N(OR5)R6 ou N(NR5R6)R6; X représente OH, N3, NR3R4 ou NR4CO2R15; Y représente H ou NHR2; R2 représente un groupe SO2R7 ou COR7; R3 représente H, alkyle C1-6 ou C(=NR8)NR9R10; R4 représente H ou alkyle C1-6, R5 représente H, alkyle C1-20, cycloalkyle C3-8, alcényle C2-20, alkynyle C2-20, CHR11COR12 ou alkyle C1-20 substitué par un ou plusieurs groupes choisis parmi NR13R14, NR13COR14, CO2R13, OR13, cycloalkyle C3-8 et un aryle facultativement substitué; chacun des R6 représente indépendamment H, alkyle C1-20, cycloalkyle C3-8, alcényle C2-20, alkynyle C2-20, aryle ou alkyle C1-4 substitué par un ou plusieurs groupes choisis parmi NR13R14, COR13, cycloalkyle C3-8, CN, N3 OR13, et un aryle facultativement substitué; ou bien R5 et R6 forment ensemble une chaîne hydrocarburée C2-6 pouvant facultativement contenir un groupe NR13 et pouvant facultativement être substituée par 1, 2, 3 ou 4 groupes choisis parmi des groupes oxo et alkyle C1-6 pouvant eux-mêmes être facultativement substitués par hydroxy ou aryle facultativement substitué; R7 représente alkyle C1-6 facultativement substitués par un ou plusieurs atomes d'halogène, cycloalkyle C3-8 ou un aryle facultativement substitué; R8, R9 et R10 représentent chacun indépendamment H, alkyle C1-6, amino, hydroxy, cyano ou nitro; R11 représente la chaîne latérale d'un acide aminé D ou L, R12 représente NR13R14, OR13 ou R13; chacun des R13 et R14 représente indépendamment H, alkyle C1-6 ou arylalkyle C1-4 facultativement substitué; R15 représente alkyle C1-6. L'invention porte également sur les dérivés pharmacocompatibles de ces composés qui s'avèrent être des inhibiteurs de la neuraminidase utiles dans le traitement des infections virales.

  化合物的化学式为（I），其中R1代表OR5，SR5，NR5R6，N（OR5）R6或N（NR5R6）R6; X代表OH，N3，NR3R4或NR4CO2R15; Y代表H或NHR2; R2代表SO2R7或COR7基团; R3代表H，C1-6烷基或C（=NR8）NR9R10; R4代表H或C1-6烷基; R5代表H，C1-20烷基，C3-8环烷基，C2-20烯基，C2-20炔基，CHR11COR12或C1-20烷基，其中该烷基被一个或多个从NR13R14，NR13COR14，CO2R13，OR13，C3-8环烷基和可选取代的芳基中选择的基团取代; 每个R6独立地代表H，C1-6烷基，C3-8环烷基，C2-6烯基，C2-20炔基，芳基或C1-4烷基，其中该烷基被一个或多个从NR13R14，COR13，C3-8环烷基，CN，N3，OR13和可选取代的芳基中选择的基团取代; 或R5和R6一起形成一个C2-6碳氢链，该链可以选择性地包含一个NR13基团，该链可以选择性地被1、2、3或4个选择自羟基或可选取代的芳基的氧代和C1-6烷基基团取代; R7代表C1-6烷基，可选择性地被一个或多个卤素原子取代，C3-8环烷基或可选取代的芳基; R8，R9和R10各自独立地代表H，C1-6烷基，氨基，羟基，氰基或硝基; R11代表D-或L-氨基酸的侧链; R12代表NR13R14，OR13或R13; 每个R13和每个R14独立地代表H，C1-6烷基或可选取代的芳基C1-4烷基; R15代表C1-6烷基; 它们的药物可接受的衍生物是神经氨酸酶抑制剂，用于治疗病毒感染。
• 6-CARBOXAMIDO DIHYDROPYRAN DERIVATIVES
  申请人：BIOTA SCIENTIFIC MANAGEMENT PTY. LTD.

  公开号：EP0833825A1

  公开（公告）日：1998-04-08
• EP0833825A4
  申请人：——

  公开号：EP0833825A4

  公开（公告）日：1998-10-07
• US5990156A
  申请人：——

  公开号：US5990156A

  公开（公告）日：1999-11-23