(3S,4S)-3-[(1S)-2-(4-氟苯氧基)-1-羟乙基]-1-(4-氟苯基)-4-(4-羟基苯基)氮杂环丁烷-2-酮 | 172139-48-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 中文名称: (3S,4S)-3-[(1S)-2-(4-氟苯氧基)-1-羟乙基]-1-(4-氟苯基)-4-(4-羟基苯基)氮杂环丁烷-2-酮
• 英文名称: Sch57939
• 英文别名: 3(S)-[2-(4-fluorophenoxy)-1(S)-hydroxyethyl]-4(S)-(4-hydroxyphenyl)-1-(4-fluorophenyl)-2-azetidinone；(3S,4S)-3-[(1S)-2-(4-fluorophenoxy)-1-hydroxyethyl]-1-(4-fluorophenyl)-4-(4-hydroxyphenyl)azetidin-2-one
• CAS: 172139-48-9
• 化学式: C₂₃H₁₉F₂NO₄
• 分子量: 411.405
• InChiKey: MMNZCESXFOCVMF-YPAWHYETSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (3S,4S)-4-(4-(苄氧基)苯基)-3-((S)-1,2-二羟基乙基)-1-(4-氟苯基)氮杂环丁-2-酮 在 吡啶 、 正丁基锂 、 5%-palladium/activated carbon 、 甲酸铵 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 91.17h， 生成 (3S,4S)-3-[(1S)-2-(4-氟苯氧基)-1-羟乙基]-1-(4-氟苯基)-4-(4-羟基苯基)氮杂环丁烷-2-酮
  参考文献：
  名称：

  A Concise Asymmetric Synthesis of A β-Lactam-Based Cholesterol Absorption Inhibitor

  摘要：

  A concise, four-step, asymmetric synthesis of a beta-lactam-based cholesterol absorption inhibitor, Sch 57939, was developed, The discovery of a one-step enantio- and diastereoselective synthesis of a trans-beta-lactam provided easy access to the desired three chiral centers. A novel zinc phenoxide-promoted ether synthesis was reported for the completion of the side chain.

  DOI：

  10.1021/op990196r

文献信息

• (−)-SCH 57939: synthesis and pharmacological properties of a potent, metabolically stable cholesterol absorption inhibitor
  作者：Michael P. Kirkup、Razia Rizvi、Bandarpalle B. Shankar、Sundeep Dugar、John W. Clader、Stuart W. McCombie、Sue-Ing Lin、Nathan Yumibe、Keith Huie、Margaret Van Heek、Douglas S. Compton、Harry R. Davis、Andrew T. McPhail

  DOI：10.1016/0960-894x(96)00365-4

  日期：1996.9

  Previous SAR studies of C-3 side chain modified analogs of (-)-SCH 48461,(1,3,4) as well as information concerning the metabolic stability this series, enabled us to design a cholesterol absorption inhibitor (i.e., (-) 2a, SCH 57939) with tenfold higher potency and greatly enhanced metabolic stability. The synthesis and pharmacological profile, including the role of relative stereochemistry at both the C3 and 1' positions in determining the SAR of these compounds, will be discussed. Copyright (C) 1996 Elsevier Science Ltd
• SUBSTITUTED AZETIDINONE COMPOUNDS USEFUL AS HYPOCHOLESTEROLEMIC AGENTS
  申请人：SCHERING CORPORATION

  公开号：EP0751934A1

  公开（公告）日：1997-01-08
• US5627176A
  申请人：——

  公开号：US5627176A

  公开（公告）日：1997-05-06
• [EN] SUBSTITUTED AZETIDINONE COMPOUNDS USEFUL AS HYPOCHOLESTEROLEMIC AGENTS<br/>[FR] COMPOSES D'AZETIDINONE SUBSTITUEE UTILES COMME AGENTS HYPOCHOLESTEROLEMIQUES
  申请人：SCHERING CORPORATION

  公开号：WO1995026334A1

  公开（公告）日：1995-10-05

  (EN) Substituted azetidinone hypocholesterolemic agents of formula (I) or a pharmaceutically acceptable salt thereof, wherein: Ar1 is R3-substituted aryl; Ar2 is R4-substituted aryl; Ar3 is R5-substituted aryl; Y and Z are independently -CH2-, -CH(lower alkyl)- or -C(dilower alkyl)-; A is -O-, -S-, -S(O)- or -S(O)2-; R1 is -OR6, -O(CO)R6, -O(CO)OR9 or -O(CO)NR6R7; R2 is hydrogen, lower alkyl or aryl; or R1 and R2 together are =O; q is 1, 2 or 3; p is 0, 1, 2, 3 or 4; R5 is 1-3 substituents independently selected from -OR6, -O(CO)R6, -O(CO)OR9, -O(CH2)1-5OR9, -O(CO)NR6R7, -NR6R7, -NR6(CO)R7, -NR6(CO)OR9, -NR6(CO)NR7R8, -NR6SO2-lower alkyl, -NR6SO2-aryl, -CONR6R7, -COR6, -SO2NR6R7, S(O)0-2-alkyl, S(O)0-2-aryl, -O(CH2)1-10-COOR6, -O(CH2)0-10CONR6R7, $i(o)-halogeno, $i(m)-halogeno, $i(o)-lower alkyl, $i(m)-lower alkyl, -(lower alkylene)-COOR6 and -CH=CH-COOR6; R3 and R4 are 1-3 substituents independently selected from R5, hydrogen, $i(p)-lower alkyl, aryl, -NO2, CF3 and $i(p)-halogeno; R6, R7 and R8 are hydrogen, lower alkyl, aryl or aryl-substituted lower alkyl; and R9 is lower alkyl, aryl or aryl-substituted lower alkyl; are disclosed, as well as a method of lowering serum cholesterol by administering said compounds, pharmaceutical compositions containing them, the combination of a substituted azetidinone and a cholesterol biosynthesis inhibitor for the treatment and prevention of atherosclerosis, novel intermediates and methods for preparing said intermediates.(FR) Cette invention concerne des agents hypocholestérolémiques à base d'azétidinone substituée de formule (I) ou un de ses sels pharmaceutiquement acceptable. Dans cette formule, Ar1 représente aryle à substitution R3; Ar2 représente aryle à substitution R4; Ar3 représente aryle à substitution R5; Y et Z représentent indépendamment -CH2-, -CH (alkyle inférieur)- ou -C(alkyle bi-inférieur)-; A représente -O-, -S-, -S(O)- ou -S(O)2; R1 représente -OR6, -O(CO)R6, -O(CO)OR9 ou -O(CO)NR6R7; R2 représente hydrogène, aryle ou alkyle inférieur; ou bien R1 et R2 représentent ensemble =O; q représente 1, 2 ou 3; p représente 0, 1, 2, 3 ou 4; R5 représente de 1 à 3 substituants indépendamment sélectionnés dans le groupe formé par: -OR6, -O(CO)R6, -O(CO)OR9, -O(CH2)1-5OR9, -O(CO)NR6R7, -NR6R7, -NR6SO2-aryle, -CONR6R7, -COR6, -SO2NR6R7, S(O)0-2-alkyle, S(O)0-2-aryle, -O(CH2)1-10-COOR6, -O(CH2)0-10CONR6R7, $i(o)-halogène, $i(m)-halogène, alkyle $i(o)-inférieur, -(alkylène inférieur)-COOR6 et -CH=CH-COOR6; R3 et R4 représentent de 1 à 3 substituants indépendamment sélectionnés dans le groupe formé par: R5, hydrogène, alkyle p-inférieur, aryle, -NO2-, CF3 et p-halogène; R6, R7 et R8 représentent hydrogène, alkyle inférieur, aryle ou alkyle inférieur à substitution aryle; et R9 représente alkyle, aryle ou alkyle inférieur à substitution aryle. On décrit également un procédé permettant de faire baisser le cholestérol sérique au moyen de l'administration des composés de cette invention, des compositions pharmaceutiques contenant ces composés, l'association d'une azétidinone substituée et d'un inhibiteur de la biosynthèse du cholestérol pour traiter et prévenir l'athérosclérose, ainsi que des nouveaux intermédiaires et des procédés de préparation de ces derniers.
• A Concise Asymmetric Synthesis of A β-Lactam-Based Cholesterol Absorption Inhibitor
  作者：George Guangzhong Wu

  DOI：10.1021/op990196r

  日期：2000.7.1

  A concise, four-step, asymmetric synthesis of a beta-lactam-based cholesterol absorption inhibitor, Sch 57939, was developed, The discovery of a one-step enantio- and diastereoselective synthesis of a trans-beta-lactam provided easy access to the desired three chiral centers. A novel zinc phenoxide-promoted ether synthesis was reported for the completion of the side chain.