(2S)-(+)-1-(3',4'-dibenzyloxyphenoxy)-2,3-epoxypropane | 177704-09-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (2S)-(+)-1-(3',4'-dibenzyloxyphenoxy)-2,3-epoxypropane
• 英文别名: (S)-2-{[3,4-bis(benzyloxy)phenoxy]methyl}oxirane；(S)-1-(3,4-dibenzyloxyphenoxy)-2,3-epoxypropane；(S)-3-(3,4-dibenzyloxyphenoxy)-1,2-epoxypropane；(2S)-2-[[3,4-bis(phenylmethoxy)phenoxy]methyl]oxirane
• CAS: 177704-09-5
• 化学式: C₂₃H₂₂O₄
• 分子量: 362.425
• InChiKey: RJNAMETVIBKNEQ-OAQYLSRUSA-N

物化性质

• 沸点：
  523.4±40.0 °C(Predicted)
• 密度：
  1.195±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  40.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S)-(+)-1-(3',4'-dibenzyloxyphenoxy)-2,3-epoxypropane 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 乙醇 为溶剂， 20.0~85.0 ℃ 、310.26 kPa 条件下， 反应 15.0h， 生成 (2S)-1-(3,4-dihydroxyphenoxy)-3-[2-(3',4'-dimethoxyphenyl)ethyl]amino-2-propanol
  参考文献：
  名称：

  Asymmetric Synthesis of (2S)‐1‐(3,4‐Dihydroxyphenoxy)‐3‐(3,′4′‐Dimethoxyphenoxy) Ethylamino‐2‐propanol hydrochloride (RO363)

  摘要：

  Enantiomerically pure (S)-RO363 was synthesized by using (R,R) Salen Co(III) complex for the resolution of terminal epoxide. The hydrolytic kinetic resolution process was carried out at room temperature in excellent enantioselectivity. The method can be applied for large-scale preparation of (S)RO363.

  DOI：

  10.1080/00397910600602651
• 作为产物：
  描述：

  3,4-二苄氧基苯甲醛 在 氢氧化钾 、 sodium hydride 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 (2S)-(+)-1-(3',4'-dibenzyloxyphenoxy)-2,3-epoxypropane
  参考文献：
  名称：

  Synthesis and β-adrenoceptor agonist properties of (±)-1-(3',4'-dihydroxyphenoxy)-3-(3",4"-dimethoxyphenyl) ethylamino-2-propanol hydrochloride, (±)-RO363.HCl, and the (2S)-(-)-isomer

  摘要：

  The synthesis of (+/-)-1-(3 ',4'-dihydroxyphenoxy)-3-(3",4"-dimethoxyphenyl)ethylamino-2-propanol hydrochloride, (+/-)R0363.HCl, and the (2S)-(-)-isomer is described for the first time. The binding affinities for (+/-)-R0363.HCl, (2S)-(-)-R0363.HCl and a number of well known beta-adrenoceptor agonists for transfected human beta(1)-, beta(2)-and beta(3),-adrenoceptors expressed in Chinese hamster ovary cells have been determined and compared with the functional potencies in rat atria (beta(1)) and trachea (beta(2)). The results indicate that both (+/-)-R0363 and (2S)-(-)-R0363 are selective for the human and rat beta(1)-adrenoceptors. The (2S)-(-)-isomer of R0363, as expected, has a higher binding affinity for the human and functional potency for rat beta-adrenoceptor subtypes than the racemate. However, in contrast to the catecholamines and formoterol, the functional potency of the racemic mixture and its (-)-enantiomer are not significantly different from their binding affinity, suggesting that they are examples of partial agonists with sufficient intrinsic activity to produce full agonist responses. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(99)80103-2

文献信息

• Derivatives of 4-(2-aminoethyl)phenoxymethyl-phosphonic and -phosphinic
  申请人：SmithKline Beecham p.l.c.

  公开号：US05726165A1

  公开（公告）日：1998-03-10

  A compound of formula (I): ##STR1## or a pharmaceutically acceptable salt, or solvate thereof, wherein, R.sup.o represents an aryl group, optionally substituted; X represents O or S; R.sup.1 and R.sup.1a each independently represents hydrogen or an alkyl group; R.sup.2 represents OCH.sub.2 CO.sub.2 H, or an ester or amide thereof, or R.sup.2 represents a moiety of formula (b): ##STR2## wherein R.sup.4 represent hydrogen, alkyl, hydroxyalkyl, arylalkyl, aralkyloxyalkyl or cycloalkyl and R.sup.5 represent hydroxy, alkoxy, arylalkyloxy, hydroxyalkyloxy, alkoxyalkyloxy, arylalkoxyalkyloxy, cycloalkyloxy, hydrogen, alkyl, substituted alkyl, cycloalkyl, aryl, arylalkyl, arylalkyloxyalkyl or R.sup.5 together with OR.sup.4 represents O(CH.sub.2).sub.n O wherein n is 2, 3 or 4; and R.sup.3 represents hydrogen, halogen, alkyl or alkoxy or R.sup.3 together with R.sup.2 represents a moiety of formula (c): ##STR3## or an ester or amide thereof; a pharmaceutical composition containing such a compound, a process of preparing such a compound and the use of such a compound in medicine.

  化合物的化学式（I）：##STR1## 或其药学上可接受的盐或溶剂化物，其中，R.sup.o代表芳基，可选地取代；X代表O或S；R.sup.1和R.sup.1a各自独立地代表氢或烷基；R.sup.2代表OCH.sub.2 CO.sub.2 H，或其酯或酰胺，或R.sup.2代表式（b）的基团：##STR2## 其中R.sup.4代表氢、烷基、羟基烷基、芳基烷基、芳基氧烷基或环烷基，R.sup.5代表羟基、烷氧基、芳基烷氧基、羟基烷氧基、烷氧基烷氧基、芳基烷氧基烷氧基、环烷氧基、氢、烷基、取代烷基、环烷基、芳基、芳基烷基、芳基烷氧基烷基或R.sup.5与OR.sup.4一起代表O(CH.sub.2).sub.n O，其中n为2、3或4；R.sup.3代表氢、卤素、烷基或烷氧基，或R.sup.3与R.sup.2一起代表式（c）的基团：##STR3## 或其酯或酰胺；包含此类化合物的药物组合物，制备此类化合物的方法以及此类化合物在医药上的用途。
• Synthesis and β-adrenoceptor agonist properties of (±)-1-(3',4'-dihydroxyphenoxy)-3-(3",4"-dimethoxyphenyl) ethylamino-2-propanol hydrochloride, (±)-RO363.HCl, and the (2S)-(-)-isomer
  作者：Dimitri Iakovidis、Simon N.S Louis、Linda A Rezmann、Felicia Colagrande、Tracy L Nero、Graham P Jackman、William J Louis

  DOI：10.1016/s0223-5234(99)80103-2

  日期：1999.6

  The synthesis of (+/-)-1-(3 ',4'-dihydroxyphenoxy)-3-(3",4"-dimethoxyphenyl)ethylamino-2-propanol hydrochloride, (+/-)R0363.HCl, and the (2S)-(-)-isomer is described for the first time. The binding affinities for (+/-)-R0363.HCl, (2S)-(-)-R0363.HCl and a number of well known beta-adrenoceptor agonists for transfected human beta(1)-, beta(2)-and beta(3),-adrenoceptors expressed in Chinese hamster ovary cells have been determined and compared with the functional potencies in rat atria (beta(1)) and trachea (beta(2)). The results indicate that both (+/-)-R0363 and (2S)-(-)-R0363 are selective for the human and rat beta(1)-adrenoceptors. The (2S)-(-)-isomer of R0363, as expected, has a higher binding affinity for the human and functional potency for rat beta-adrenoceptor subtypes than the racemate. However, in contrast to the catecholamines and formoterol, the functional potency of the racemic mixture and its (-)-enantiomer are not significantly different from their binding affinity, suggesting that they are examples of partial agonists with sufficient intrinsic activity to produce full agonist responses. (C) Elsevier, Paris.
• ARYLOXY AND ARYLTHIOPROPANOLAMINE DERIVATIVES USEFUL AS BETA 3-ADRENORECEPTOR AGONISTS AND ANTAGONISTS OF THE BETA 1 AND BETA 2-ADRENORECEPTORS AND PHARMACEUTICAL COMPOSITION THEREOF
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0772585A1

  公开（公告）日：1997-05-14
• US5726165A
  申请人：——

  公开号：US5726165A

  公开（公告）日：1998-03-10
• [EN] ARYLOXY AND ARYLTHIOPROPANOLAMINE DERIVATIVES USEFUL AS BETA 3-ADRENORECEPTOR AGONISTS AND ANTAGONISTS OF THE BETA 1 AND BETA 2-ADRENORECEPTORS AND PHARMACEUTICAL COMPOSITION THEREOF<br/>[FR] DERIVES D'ARYLOXY- ET D'ARYLTHIOPROPANOLAMINE UTILES EN TANT QU'AGONISTES D'ADRENORECEPTEURS BETA 3 ET QU'ANTAGONISTES DES ADRENORECEPTEURS BETA 1 ET BETA 2 ET COMPOSITION PHARMACEUTIQUE
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO1996004233A1

  公开（公告）日：1996-02-15

  (EN) A compound formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein R0 represents an aryl group optionally substituted with one, two or three substituents selected from the list consisting of: hydroxy, hydroxymethyl, nitro, amino, alkylamino, dialkylamino, alkylsulphonamido, arylsulphonamido, formamido, halogen, alkoxy and allyl; X represents O or S; R1 and R1a each independently represents hydrogen or an alkyl group; R2 represents OCH2CO2H, or an ester or amide thereof, or R2 represents a moiety of formula (b), wherein R4 represents hydrogen, alkyl, hydroxyalkyl, arylalkyl, aryloxyalkyl, aralkyloxyalkyl or cycloalkyl and R5 represents hydroxy, alkoxy, arylalkyloxy, hydroxyalkyloxy, alkoxyalkyloxy, aryloxyalkyloxy, arylalkoxyalkyloxy or cycloalkyloxy or R5 represents hydrogen, alkyl, substituted alkyl, cycloalkyl, aryl, arylalkyl, aryloxyalkyl, arylalkyloxyalkyl or R5 together with OR4 represents O(CH2)nO, wherein n is 2, 3 or 4; and R3 represents hydrogen, halogen, alkyl or alkoxy or R3 together with R2 represents a moiety of formula (c) or an ester or amide thereof; providing that 4-[2-[2-hydroxy-3-(4-hydroxyphenoxy)propylamino]propyl]phenoxyacetic acid and salts and esters thereof and the compounds of examples 1 to 36 disclosed in EP0328251 are excluded from the scope of formula (I); a pharmaceutical composition containing such a compound, a process of preparing such a compound and the use of such a compound in medicine.(FR) Composé de formule (I) ou sel ou solvat pharmaceutiquement acceptables dudit composé, dans laquelle Ro représente un groupe aryle éventuellement substitué à l'aide d'un, deux ou trois substituants choisis dans la liste comprenant hydroxy, hydroxyméthyle, nitro, amino, alkylamino, dialkylamino, alkylsulphonamido, arylsulphonamido, formamido, halogène, alcoxy et allyle; X représente O ou S; R1 et R1a représentent chacun indépendamment hydrogène ou un groupe alkyle; R2 représente OCH2CO2H, ou un ester ou amide de ladite substance, ou R2 représente une fraction de formule (b) dans laquelle R4 représente hydrogène, alkyle, hydroxyalkyle, arylalkyle, aryloxyalkyle, aralkyloxyalkyle ou cycloalkyle et R5 représente hydroxy, alcoxy, arylalkyloxy, hydroxyalkyloxy, alcoxyalkyloxy, aryloxyalkyloxy, arylalcoxyalkyloxy ou cycloalkyloxy ou R5 représente hydrogène, alkyle, alkyle substitué, cycloalkyle, aryle, arylakyle, aryloxyalkyle, arylalkyloxyalkyle ou R5 combiné à OR4 représente O(CH2)nO dans laquelle n est 2, 3 ou 4; et R3 représente hydrogène, halogène, alkyle ou alcoxy ou R3 combiné à R2 représente une fraction de formule (c) ou un ester ou amide de ladite fraction; à condition que l'acide 4-[2-[2-hydroxy-3-(4-hydroxyphénoxy)propylamino] phénoxyacétique et les sels et esters dudit acide ainsi que les composés des exemples 1 à 36 décrits dans EP0328251 soient exclus de la portée de la présente invention. Une composition pharmaceutique contenant ledit composé, un procédé de préparation d'un composé de ce type et l'utilisation de ce composé en médecine sont également décrits.