ethyl 3-(3-allyl-4-trifluoromethylsulphonyloxyphenyl)propionate | 166959-23-5

• 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: ethyl 3-(3-allyl-4-trifluoromethylsulphonyloxyphenyl)propionate
• 英文别名: ethyl 3-[3-prop-2-enyl-4-(trifluoromethylsulfonyloxy)phenyl]propanoate
• CAS: 166959-23-5
• 化学式: C₁₅H₁₇F₃O₅S
• 分子量: 366.358
• InChiKey: GVORNBDFGJPERQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  78
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 3-(3-allyl-4-trifluoromethylsulphonyloxyphenyl)propionate 在 bis-triphenylphosphine-palladium(II) chloride 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.0h， 生成 3-[3-Allyl-4-(3-hydroxy-1-aza-bicyclo[2.2.2]oct-3-ylethynyl)-phenyl]-N-methyl-propionamide
  参考文献：
  名称：

  Novel optimised quinuclidine squalene synthase inhibitors

  摘要：

  Optimised quinuclidine squalene synthase (SQS) inhibitors are reported; 3-[2-(2-allyl-4-(2-ethoxy carbonylethyl)phenyl)ethynyl]quinuclidin-3-ol 1c, is a potent inhibitor of rat (KI = 6 nM) and human (KI = 43 nM) microsomal SQS; the oral ED(50) of 1c, for the inhibition of rat cholesterol biosynthesis was 1.3+/-0.45 mg/kg and for the R-enantiomer 1m, 0.8+/-0.2 mg/kg, with the corresponding R-carboxylic acid 6a, being 0.9+/-0.25 mg/kg. (C) 1997 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(97)00053-x
• 作为产物：
  描述：

  对羟基苯丙酸乙酯 在 potassium carbonate 、 三乙胺 作用下， 以 二苯醚 、 二氯甲烷 、 丁酮 为溶剂， 生成 ethyl 3-(3-allyl-4-trifluoromethylsulphonyloxyphenyl)propionate
  参考文献：
  名称：

  Novel optimised quinuclidine squalene synthase inhibitors

  摘要：

  Optimised quinuclidine squalene synthase (SQS) inhibitors are reported; 3-[2-(2-allyl-4-(2-ethoxy carbonylethyl)phenyl)ethynyl]quinuclidin-3-ol 1c, is a potent inhibitor of rat (KI = 6 nM) and human (KI = 43 nM) microsomal SQS; the oral ED(50) of 1c, for the inhibition of rat cholesterol biosynthesis was 1.3+/-0.45 mg/kg and for the R-enantiomer 1m, 0.8+/-0.2 mg/kg, with the corresponding R-carboxylic acid 6a, being 0.9+/-0.25 mg/kg. (C) 1997 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(97)00053-x

文献信息

• Heterocyclic derivatives
  申请人：Zeneca Limited

  公开号：US05919793A1

  公开（公告）日：1999-07-06

  Compounds of formula (I) wherein R.sup.1 is hydrogen or hydroxy; R.sup.2 is hydrogen; or R.sup.1 and R.sup.2 are joined together so that CR.sup.1 14 CR.sup.2 is a double bond; X is selected from --Ch.sub.2 CH.sub.2 --, --C.dbd.CH--, --C.tbd.C--, --CH.sub.2 O--, --OCH.sub.2, CH.sub.2 NH--, --NHCH.sub.2 --, --CH.sub.2 CO--, --COCH.sub.2 --, --CH.sub.2 S(O).sub.n -- and --S(O).sub.n CH.sub.2 -- (wherein n is 0, 1 or 2); Ar is phenyl which bears one or more substituents independently selected from the groups (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, (1-6C)alkoxycarbonyl, (1-6C)alkoxycarbonyl(1-6C)alkyl, (1-6C)alkoxy(1-6C)alkyl, (1-6C)alkylamino, di-\x9b(1-6C)alkyl!amino, carbamoyl, (1-6C) alkylcarbamoyl, di-\x9b(1-6C)alkyl!carbamoyl, (1-6C)alkenyl and oxime derivatives thereof and O--(1-6C)alkyl ethers of said oximes (1-6C)alkylthio, (1-6C)alkylsulphinyl and (1-6C)alkylsulphonyl when substituted by one or more groups selected from (1-6C)alkoxycarbonyl, (1-6C)alkanoyl and oxime derivatives thereof and O-(1-6C)alkyl ethers of said oxime derivatives, (1-6C)alkanoylamimo, (1-6C)alkanoyloxy, (1-6C)alkanoyloxy(1-6)alkyl, carbamoyl, N-(1-6C)alkylcarbamoyl, N,N-di\x9b(1-6C)alkyl!carbamoyl, amino, (1-6C)alkylamino, di-\x9b(1-6C)alkyl!amino, (1-6C)alkoxy, (2-6C)alkenyloxy, (1-6C)alkylthio, (1-6C)alkylsulphinyl, (1-6C)alkylsulphonyl, halogeno(1-6C)alkyl (2-6C)alkenyl, (2-6C)alkynyl, phenyl, phenoxy, cyano, nitro, hydroxy and carboxy; and wherein Ar may bear further substituents; and their pharmaceutically acceptable salts inhibit squalene synthese and are hence useful in lowering cholesterol levels in blood plasma Processes for preparing compounds of formula (I) are also referred to as well as pharmaceutical compositions containing them and their use in medicine.

  式(I)中的化合物，其中R.sup.1是氢或羟基；R.sup.2是氢；或R.sup.1和R.sup.2结合在一起，使得CR.sup.1 14 CR.sup.2是一个双键；X从--Ch.sub.2 CH.sub.2 --，--C.dbd.CH--，--C.tbd.C--，--CH.sub.2 O--，--OCH.sub.2，CH.sub.2 NH--，--NHCH.sub.2 --，--CH.sub.2 CO--，--COCH.sub.2 --，--CH.sub.2 S(O).sub.n --和--S(O).sub.n CH.sub.2 --中选择（其中n为0、1或2）；Ar是苯基，其上独立选择自基团（1-6C）烷基，（2-6C）烯基，（2-6C）炔基，（1-6C）烷氧基，（1-6C）烷氧羰基，（1-6C）烷氧羰基（1-6C）烷基，（1-6C）烷氧基（1-6C）烷基，（1-6C）烷基氨基，二-\x9b（1-6C）烷基！氨基，氨基甲酰基，（1-6C）烷基甲酰基，二-\x9b（1-6C）烷基！甲酰基，（1-6C）烯基和其氧肟衍生物和所述氧肟的O-（1-6C）烷基醚（1-6C）烷硫基，（1-6C）烷磺基和（1-6C）烷磺基，当被一个或多个基团选择时，从（1-6C）烷氧羰基，（1-6C）烷酰基和其氧肟衍生物和所述氧肟衍生物的O-（1-6C）烷基醚，（1-6C）烷酰胺基，（1-6C）烷酰氧基，（1-6C）烷酰氧基（1-6）烷基，氨基甲酰基，N-（1-6C）烷基甲酰基，N，N-二\x9b（1-6C）烷基！甲酰基，氨基，（1-6C）烷基氨基，二-\x9b（1-6C）烷基！氨基，（1-6C）烷氧基，（2-6C）烯氧基，（1-6C）烷硫基，（1-6C）烷磺基，（1-6C）烷磺基，卤代（1-6C）烷基（2-6C）烯基，（2-6C）炔基，苯基，苯氧基，氰基，硝基，羟基和羧基；其中Ar可能带有进一步的取代基；它们的药学上可接受的盐抑制角鲨烯合成，因此在降低血浆胆固醇水平方面有用。制备式(I)化合物的方法也被提及，以及含有它们的药物组合物及其在医学中的用途。
• HETEROCYCLIC DERIVATIVES
  申请人：ZENECA LIMITED

  公开号：EP0696284A1

  公开（公告）日：1996-02-14
• US5919793A
  申请人：——

  公开号：US5919793A

  公开（公告）日：1999-07-06
• [EN] HETEROCYCLIC DERIVATIVES<br/>[FR] DERIVES HETEROCYCLIQUES
  申请人：ZENECA LIMITED

  公开号：WO1994025459A1

  公开（公告）日：1994-11-10

  (EN) Compounds of formula (I) wherein R1 is hydrogen or hydroxy; R2 is hydrogen; or R1 and R2 are joined together so that CR1-CR2 is a double bond; X is selected from -CH2CH2-, -CH=CH-, -C$m(Z)C-, -CH2O-, -OCH2-, CH2NH-, -NHCH2-, -CH2CO-, -COCH2-, -CH2S(O)n- and -S(O)nCH2- (wherein n is 0, 1 or 2); Ar is phenyl which bears one or more substituents independently selected from the groups (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, (1-6C)alkoxycarbonyl, (1-6C)alkoxycarbonyl(1-6C)alkyl, (1-6C)alkoxy(1-6C)alkyl, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, carbamoyl, (1-6C) alkylcarbamoyl, di-[(1-6C)alkyl]carbamoyl, (1-6C)alkanoyl and oxime derivatives thereof and O-(1-6C)alkyl ethers of said oximes, (1-6C)alkylthio, (1-6C)alkylsulphinyl and (1-6C)alkylsulphonyl when substituted by one or more groups selected from (1-6C)alkoxycarbonyl, (1-6C)alkanoyl and oxime derivatives thereof and O-(1-6C)alkyl ethers of said oxime derivatives, (1-6C)alkanoylamino, (1-6C)alkanoyloxy, (1-6C)alkanoyloxy(1-6C)alkyl, carbamoyl, N-(1-6C)alkylcarbamoyl, N,N-di[(1-6C)alkyl]carbamoyl, amino, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, (1-6C)alkoxy, (2-6C)alkenyloxy, (1-6C)alkylthio, (1-6C)alkylsulphinyl, (1-6C)alkylsulphonyl, halogeno(1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, phenyl, phenoxy, cyano, nitro, hydroxy and carboxy; and wherein Ar may bear further substituents; and their pharmaceutically acceptable salts inhibit squalene synthese and are hence useful in lowering cholesterol levels in blood plasma. Processes for preparing compounds of formula (I) are also referred to as well as pharmaceutical compositions containing them and their use in medicine.(FR) L'invention concerne des composés de la formule (I) dans laquelle R1 représente hydrogène ou hydroxy; R2 représente hydrogène; ou R1 et R2 sont reunis de sorte que CR1-CR2 forme une double liaison; X est sélectionné à partir de -CH2CH2-, -CH=CH-, -C$m(Z)C-, -CH2O-, -OCH2-, CH2NH-, -NHCH2-, -CH2CO-, -COCH2-, -CH2S(O)n- and -S(O)nCH2- (où n vaut 0, 1 ou 2); Ar représente phényle qui porte un ou plusieurs substituants indépendamment sélectionnés dans les groupes (1-6)alkyle, (2-6C)alcényle, (2-6C)alkynyle, (1-6C)alcoxy, (1-6C)alcoxycarbonyle, (1-6C)alcoxycarbonyl(1-6C)alkyle, (1-6C)alcoxy(1-6C)alkyle, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, carbamoyle, (1-6C)alkylcarbamoyle, di-[(1-6C)alkyl]carbamoyle, (1-6C)alcanoyle et des dérivés d'oxime de ceux-ci, et des éthers O-(1-6C)alkyl de ces oximes, (1-6C)alkylthio, (1-6C)alkylsulphinyle et (1-6C)alkylsulphonyle lorsqu'ils sont substitués par un ou plusieurs groupes sélectionnés à partir de (1-6C)alcoxycarbonyle, (1-6C)alcanoyle et des dérivés d'oxime de ceux-ci, et des éthers O-(1-6C)alkyle de ces dérivés d'oxime, (1-6C)alcanoylamino, (1-6C)alcanoyloxy, (1-6C)alcanoyloxy(1-6C)alkyle, carbamoyle, N-(1-6C)alkylcarbamoyle, N,N-di[(1-6C)alkyl]carbamoyle, amino, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, (1-6C)alcoxy, (2-6C)alcényloxy, (1-6C)alkylthio, (1-6C)alkylsulphinyle, (1-6C)alkylsulphonyle, halogéno(1-6C)alkyle, (2-6C)alcényle, (2-6C)alkynyle, phényle, phénoxy, cyano, nitro, hydroxy et carboxy; et où Ar peut porter d'autres substituants; et leurs sels pharmaceutiquement acceptables inhibent la synthase squaléne et sont par conséquent utiles dans la réduction des taux de cholestérol dans le plasma sanguin. L'invention concerne également des procédés de préparation des composés de la formule (I) et des compositions pharmaceutiques les contenant ainsi que leur utilisation en médicine.
• Novel optimised quinuclidine squalene synthase inhibitors
  作者：George R. Brown、Alan J. Foubister、Susan Freeman、Fergus McTaggart、Donald J. Mirrlees、Alan C. Reid、Graham J. Smith、Melvyn J. Taylor、Douglas A. Thomason、Paul R.O. Whittamore

  DOI：10.1016/s0960-894x(97)00053-x

  日期：1997.3

  Optimised quinuclidine squalene synthase (SQS) inhibitors are reported; 3-[2-(2-allyl-4-(2-ethoxy carbonylethyl)phenyl)ethynyl]quinuclidin-3-ol 1c, is a potent inhibitor of rat (KI = 6 nM) and human (KI = 43 nM) microsomal SQS; the oral ED(50) of 1c, for the inhibition of rat cholesterol biosynthesis was 1.3+/-0.45 mg/kg and for the R-enantiomer 1m, 0.8+/-0.2 mg/kg, with the corresponding R-carboxylic acid 6a, being 0.9+/-0.25 mg/kg. (C) 1997 Elsevier Science Ltd. All rights reserved.