2-(1,2-diphenylethyl)-3-oxo-1-azabicyclo<2.2.2>octane | 172035-65-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 2-(1,2-diphenylethyl)-3-oxo-1-azabicyclo<2.2.2>octane
• 英文别名: 2-(1,2-Diphenylethyl)-3-oxo-1azabicyclo[2.2.2]octane；2-(1,2-Diphenylethyl)-3-oxo1-azabicyclo [2.2.2]octane；2-(1,2-diphenylethyl)-1-azabicyclo[2.2.2]octan-3-one
• CAS: 172035-65-3；147373-72-6；147373-75-9
• 化学式: C₂₁H₂₃NO
• 分子量: 305.42
• InChiKey: GUIWWUFDXPOTGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(1,2-diphenylethyl)-3-oxo-1-azabicyclo<2.2.2>octane 在 lithium aluminium tetrahydride 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 6.0h， 生成 3-<<(3,5-dimethylphenyl)methyl>oxy>-2-(1,2-diphenylethyl)-1-azabicyclo<2.2.2>octane
  参考文献：
  名称：

  Identification of a Series of 3-(Benzyloxy)-1-azabicyclo[2.2.2]octane Human NK1 Antagonists

  摘要：

  The synthesis and in vitro and in vivo evaluation of a series of 3-(benzyloxy)-1-azabicyclo[2.2.2]octane NK1 antagonists are described. While a number of 3,5-disubstituted benzyl ethers afford high affinity, the 3,5-bis(trifluoromethyl)benzyl was found to combine high in vitro affinity with good oral activity. Detailed structure-activity relationship studies in conjunction with data from molecular modeling and mutagenesis work have allowed the construction of a model of the pharmacophore. Specific interactions that have been identified include an interaction between His-197 and one of the rings of the benzhydryl, a Lipophilic pocket containing His-265 that the benzyl ether occupies, and a possible hydrogen bond between Gln-165 and the oxygen of the benzyl ether.

  DOI：

  10.1021/jm00024a007
• 作为产物：
  描述：

  (Z)-2-benzylidene-1-azabicyclo[2.2.2]octan-3-one 、 苄基氯化镁 以 乙醚 、 二甲基亚砜 为溶剂， 生成 2-(1,2-diphenylethyl)-3-oxo-1-azabicyclo<2.2.2>octane
  参考文献：
  名称：

  Identification of a Series of 3-(Benzyloxy)-1-azabicyclo[2.2.2]octane Human NK1 Antagonists

  摘要：

  The synthesis and in vitro and in vivo evaluation of a series of 3-(benzyloxy)-1-azabicyclo[2.2.2]octane NK1 antagonists are described. While a number of 3,5-disubstituted benzyl ethers afford high affinity, the 3,5-bis(trifluoromethyl)benzyl was found to combine high in vitro affinity with good oral activity. Detailed structure-activity relationship studies in conjunction with data from molecular modeling and mutagenesis work have allowed the construction of a model of the pharmacophore. Specific interactions that have been identified include an interaction between His-197 and one of the rings of the benzhydryl, a Lipophilic pocket containing His-265 that the benzyl ether occupies, and a possible hydrogen bond between Gln-165 and the oxygen of the benzyl ether.

  DOI：

  10.1021/jm00024a007

文献信息

• Azabicyclic compounds, pharmaceutical compositions containing them and
  申请人：Merck Sharp & Dohme Limited

  公开号：US05288730A1

  公开（公告）日：1994-02-22

  Compounds of formula (I), and salts and prodrugs thereof: ##STR1## wherein Q is the residue of an optionally substituted azabicyclic ring system; X represents oxa or thia; Y represents H or hydroxy; R.sup.1 represents phenyl or thienyl, either of which groups may be optionally substituted by halo, trifluoromethyl or C.sub.1-3 alkoxy, or C.sub.5-7 cycloalkyl; R.sup.2 represents benzyl which may be substituted in the benzyl ring by halo, trifluoromethyl or C.sub.1-3 alkoxy, or C.sub.5-7 cycloalkyl; and R.sup.3, R.sup.4 and R.sup.5 independently represent H, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halo, cyano, nitro, trifluoromethyl, trimethylsilyl, --OR.sup.a, SCH.sub.3, SOCH.sub.3, S0.sub.2 CH.sub.3, --NR.sup.a R.sup.b, --NR.sup.a COR.sup.b, --NR.sup.a C0.sub.2 R.sup.b, --C0.sub.2 R.sup.a or --CONR.sup.a R.sup.b ; and R.sup.a and R.sup.b independently represent H, C.sub.1-6 alkyl, phenyl or trifluoromethyl, are tachykinin receptor antagonists. They and compositions thereof are useful in therapy.

  式（I）的化合物，以及其盐和前药：##STR1## 其中Q是可选取代的氮杂双环环系的残基; X代表氧杂或硫杂; Y代表H或羟基; R.sup.1代表苯基或噻吩基，其中任一基团可以可选地被卤素，三氟甲基或C.sub.1-3烷氧基，或C.sub.5-7环烷基取代; R.sup.2代表苄基，苄基环可以被卤素，三氟甲基或C.sub.1-3烷氧基，或C.sub.5-7环烷基取代; R.sup.3，R.sup.4和R.sup.5独立地代表H，C.sub.1-6烷基，C.sub.2-6烯基，C.sub.2-6炔基，卤素，氰基，硝基，三氟甲基，三甲基硅基，--OR.sup.a，SCH.sub.3，SOCH.sub.3，S0.sub.2 CH.sub.3，--NR.sup.a R.sup.b，--NR.sup.a COR.sup.b，--NR.sup.a C0.sub.2 R.sup.b，--C0.sub.2 R.sup.a或--CONR.sup.a R.sup.b; R.sup.a和R.sup.b独立地代表H，C.sub.1-6烷基，苯基或三氟甲基，它们是缓激肽受体拮抗剂。它们及其组合物在治疗中有用。
• Azabicyclic compounds, pharmaceutical compositions containing them and their use in therapy
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP0520555A1

  公开（公告）日：1992-12-30

  Compounds of formula (I), and salts and prodrugs thereof: wherein    Q is the residue of an optionally substituted azabicyclic ring system;    X represents oxa or thia;    Y represents H or hydroxy;    R¹ represents phenyl or thienyl, either of which groups may be optionally substituted by halo, trifluoromethyl or C₁₋₃ alkoxy, or C₅₋₇ cycloalkyl;    R² represents benzyl which may be substituted in the benzyl ring by halo, trifluoromethyl or C₁₋₃alkoxy, or C₅₋₇ cycloalkyl; and    R³, R⁴ and R⁵ independently represent H, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halo, cyano, nitro, trifluoromethyl, trimethylsilyl, -ORa, SCH₃, SOCH₃, SO₂CH₃, -NRaRb, -NRaCORb, -NRaCO₂Rb, -CO₂Ra or -CONRaRb; and    Ra and Rb independently represent H, C₁₋₆ alkyl, phenyl or trifluoromethyl, are tachykinin receptor antagonists. They and compositions thereof are useful in therapy.

  式（I）化合物及其盐类和原药： 其中 Q 是任选取代的氮杂环系统的残基； X 代表氧或硫 Y 代表 H 或羟基 R¹ 代表苯基或噻吩基，其中任一基团可任选被卤、三氟甲基或 C₁₋₃ 烷氧基或 C₅₋₇ 环烷基取代； R² 代表苄基，可在苄基环上被卤代、三氟甲基或 C₁₋₃ 烷氧基或 C₅₋₇ 环烷基取代；以及 R³、R⁴ 和 R⁵ 独立地代表 H、C₁₋₆ 烷基、C₂₋₆ 烯基、C₂₋₆ 炔基、卤代、氰基、硝基、三氟甲基、硝基、三氟甲基、三甲基硅基、-ORa、SCH₃、SOCH₃、SO₂CH₃、-NRaRb、-NRaCORb、-NRaCO₂Rb、-CO₂Ra 或 -CONRaRb；和 Ra 和 Rb 独立地代表 H、C₁₋₆ 烷基、苯基或三氟甲基，它们是速激肽受体拮抗剂。它们及其组合物可用于治疗。
• US5288730A
  申请人：——

  公开号：US5288730A

  公开（公告）日：1994-02-22
• Identification of a Series of 3-(Benzyloxy)-1-azabicyclo[2.2.2]octane Human NK1 Antagonists
  作者：Christopher J. Swain、Eileen M. Sewart、Margaret A. Cascieri、Tung M. Fong、Richard Herbert、D Euan MacIntyre、Kevin J. Merchant、Simon N. Owen、Andrew P. Owens

  DOI：10.1021/jm00024a007

  日期：1995.11

  The synthesis and in vitro and in vivo evaluation of a series of 3-(benzyloxy)-1-azabicyclo[2.2.2]octane NK1 antagonists are described. While a number of 3,5-disubstituted benzyl ethers afford high affinity, the 3,5-bis(trifluoromethyl)benzyl was found to combine high in vitro affinity with good oral activity. Detailed structure-activity relationship studies in conjunction with data from molecular modeling and mutagenesis work have allowed the construction of a model of the pharmacophore. Specific interactions that have been identified include an interaction between His-197 and one of the rings of the benzhydryl, a Lipophilic pocket containing His-265 that the benzyl ether occupies, and a possible hydrogen bond between Gln-165 and the oxygen of the benzyl ether.