2,2-Diphenyl-1,3,5,6,8,8a-hexahydroindolizin-7-one | 115031-85-1

• 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: 2,2-Diphenyl-1,3,5,6,8,8a-hexahydroindolizin-7-one
• CAS: 115031-85-1
• 化学式: C₂₀H₂₁NO
• 分子量: 291.393
• InChiKey: IWBIPQJCOGNSLR-UHFFFAOYSA-N

物化性质

• 沸点：
  451.0±45.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 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：

  2,2-Diphenyl-1,3,5,6,8,8a-hexahydroindolizin-7-one 在 吡啶 、 sodium hydroxide 、 戊醇 、 盐酸羟胺 、 sodium 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 (7α,8aβ)-4-amino-5-chloro-2-methoxy-N-(octahydro-2,2-diphenylindolizin-7-yl)benzamide
  参考文献：
  名称：

  Substituted benzamides with conformationally restricted side chains. 2. Indolizidine derivatives as central dopamine receptor antagonists

  摘要：

  The substituted benzamides metoclopramide (1) and clebopride (3) are stimulants of gastric motility. They are also central dopamine receptor antagonists with 3 being the more potent. This is presumed to be due to an additional interaction of its N-benzyl group with the receptor. The effect of restricting the conformation of this group by replacing the N-benzylpiperidine side chain of 3 by phenyl-substituted quinolizidines and indolizidines has been investigated. Only the indolizidines had significant activity, the nature of which depended upon the orientation of the phenyl substituent. The 2 alpha-phenyl isomers 5d-h were potent central dopamine D2 receptor antagonists with 5h showing selectivity for the limbic system. The 2 beta-phenyl isomer 5c was a gastric motility stimulant devoid of significant central dopamine receptor antagonist activity. Implications on receptor models are discussed.

  DOI：

  10.1021/jm00117a008
• 作为产物：
  描述：

  二苯乙腈 在 aluminium hydride 、 盐酸 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 55.0h， 生成 2,2-Diphenyl-1,3,5,6,8,8a-hexahydroindolizin-7-one
  参考文献：
  名称：

  Substituted benzamides with conformationally restricted side chains. 2. Indolizidine derivatives as central dopamine receptor antagonists

  摘要：

  The substituted benzamides metoclopramide (1) and clebopride (3) are stimulants of gastric motility. They are also central dopamine receptor antagonists with 3 being the more potent. This is presumed to be due to an additional interaction of its N-benzyl group with the receptor. The effect of restricting the conformation of this group by replacing the N-benzylpiperidine side chain of 3 by phenyl-substituted quinolizidines and indolizidines has been investigated. Only the indolizidines had significant activity, the nature of which depended upon the orientation of the phenyl substituent. The 2 alpha-phenyl isomers 5d-h were potent central dopamine D2 receptor antagonists with 5h showing selectivity for the limbic system. The 2 beta-phenyl isomer 5c was a gastric motility stimulant devoid of significant central dopamine receptor antagonist activity. Implications on receptor models are discussed.

  DOI：

  10.1021/jm00117a008

文献信息

• Heteroaryl-substituted pyrrole derivatives, their preparation and their therapeutic uses
  申请人：SANKYO COMPANY, LIMITED

  公开号：US20040054173A1

  公开（公告）日：2004-03-18

  Compounds having activity against production of an inflammatory cytokine of formula (I)′: 1 A′ is pyrrole; R 1′ is phenyl or naphthyl; R 2′ is pyridyl or pyrimidinyl; R 3′ is (IIa)′, (IIb)′ or (IIc)′: 2 m′ is 1; E′ is nitrogen; D′ is >C(R 5′ )—, R 5′ is hydrogen, Substituent &agr;′ or Substituent &bgr;′; B′ is nitrogen-containing 5-membered heterocyclic; R 4′ is 1 to 3 substituents from Substituent &agr;′, Substituent &bgr;′ and Substituent &ggr;′; R 1′ and R 3′ are bonded to two atoms of the pyrrole adjacent to the pyrrole atom bonded to R 2′ ; Substituent &agr;′ is hydroxyl, nitro, cyano, halogen, alkoxy, halogeno alkoxy, alkylthio, halogeno alkylthio or —NR a′ R b′ ; R a′ and R b′ are hydrogen, alkyl, alkenyl, alkynyl, aralkyl or alkylsulfonyl, or R a′ and R b′ with the nitrogen atom form a heterocyclyl; Substituent &bgr;′ is alkyl, alkenyl, alkynyl, aralkyl or cycloalkyl; Substituent &ggr;′ is oxo, hydroxyimino, alkoxyimino, alkylene, alkylenedioxy, alkylsulfinyl, alkylsulfonyl, aryl, aryloxy, alkylidenyl or aralkylidenyl.

  具有对抗公式(I)′炎症细胞因子生成活性的化合物： 1 A′是吡咯；R 1′ 是苯基或萘基；R 2′ 是吡啶基或嘧啶基；R 3′ 是(IIa)′，(IIb)′或(IIc)′： 2 m′是1；E′是氮；D′是>C(R 5′ )—, R 5′ 是氢，取代基α′或取代基β′；B′是含氮的5-成员杂环；R 4′ 是来自取代基α′，取代基β′和取代基γ′的1至3个取代基；R 1′ 和R 3′ 分别与吡咯环上与R 2′ 相连的吡咯原子的两个相邻原子成键；取代基α′是羟基，硝基，氰基，卤素，烷氧基，卤代烷氧基，烷基亚砜，卤代烷基亚砜或—NR a′ R b′ ；R a′ 和R b′ 是氢，烷基，烯基，炔基，芳烷基或烷基亚磺酰基，或者R a′ 和R b′ 与氮原子形成杂环；取代基β′是烷基，烯基，炔基，芳烷基或环烷基；取代基γ′是氧代，羟基亚胺，烷氧基亚胺，亚烷基，亚烷基二氧，烷基亚磺酰基，烷基亚磺酰基，芳基，芳氧基，亚烷基或芳亚烷基。
• PYRROLE DERIVATES FOR TREATING CYTOKINE MEDIATED DISEASES
  申请人：Sankyo Company Limited

  公开号：EP1377577A1

  公开（公告）日：2004-01-07
• US7122666B2
  申请人：——

  公开号：US7122666B2

  公开（公告）日：2006-10-17
• [EN] PYRROLE DERIVATES FOR TREATING CYTOKINE MEDIATED DISEASES<br/>[FR] DERIVES DE PYRROLE POUR TRAITER DES MALADIES DANS LESQUELLES INTERVIENNENT DES CYTOKINES
  申请人：SANKYO CO

  公开号：WO2002057264A1

  公开（公告）日：2002-07-25

  Compounds of formula (I): [wherein: A is a pyrrole ring; R1 is an optionally substituted aryl or heteroaryl group; R2 is an optionally substituted nitrogen-containing heteroaryl group; and R3 is formulae (IIa), (IIb) or (IIc), wherein m is 1 or 2, one of D and E is nitrogen and the other is ⊃C(R5)- (wherein R5 is hydrogen, a Substituent ≡ or a Substituent β), B is a nitrogen-containing 4- to 7-membered heterocyclic ring, and R4 is from 1 to 3 substituents from Substituent group ≡, substituent group β and Substituent group η; PROVIDED THAT R?1 and R3¿ are bonded to the two atoms of said pyrrole ring which are adjacent to the atom of the pyrrole ring to which said substituent R2 is bonded; Substituent group ≡ consists of hydroxyl, nitro, cyano, halogen, alkoxy, halogeno alkoxy, alkylthio and halogeno alkythio groups and groups of formula NRaRb (wherein R?a and Rb¿ are hydrogen, alkyl, alkenyl, alkynyl, aralkyl and alkylsulfonyl, or R?a and Rb¿, taken together with the nitrogen atom to which they are attached, form a heterocyclyl); Substituent group β consists of optionally substituted alkyl, alkenyl and alkynyl groups, and aralkyl and cycloalkyl groups; Substituents group η consists of oxo, hydroxyimino, alkoxyimino, alkylene, alkylenedioxy, alkylsufinyl, alkylsulfonyl, optionally substituted aryl, optionally substituted aryloxy, alkylidenyl and aralkylidenyl groups] have excellent activity against the production of inflammatory cytokines.