1-(4-chlorophenyl)-4-cyanomethyl-2-oxo-pyrrolidine | 133748-65-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 1-(4-chlorophenyl)-4-cyanomethyl-2-oxo-pyrrolidine
• 英文别名: 1-(4-Chlorophenyl)-4-cyanomethyl-2-pyrrolidone；2-[1-(4-Chlorophenyl)-5-oxopyrrolidin-3-yl]acetonitrile
• CAS: 133748-65-9
• 化学式: C₁₂H₁₁ClN₂O
• 分子量: 234.685
• InChiKey: VPSIIOXKGVHBNG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(4-chlorophenyl)-4-cyanomethyl-2-oxo-pyrrolidine 在 sodium hydroxide 、 硫酸 、 水 作用下， 以 乙醇 为溶剂， 反应 23.0h， 生成 methyl 1-(4-chlorophenyl)-5-oxo-pyrrolidine-3-acetate
  参考文献：
  名称：

  Synthesis of 4-[1-(substituted phenyl)-2-oxo-pyrrolidin-4-yl]methyloxybenzoic acids and related compounds, and their inhibitory capacities toward fatty-acid and sterol biosyntheses

  摘要：

  The synthesis of a series of 4[1-(substituted phenyl)-2-oxo-pyrrolidin-4-yl]methyloxybenzoic acids and related compounds, and their evaluation for inhibitory capacity toward fatty-acid and sterol biosyntheses using rats' liver slices in vitro and rabbits in vivo, are described. Among the compounds synthesized, 7e, 7g, 7h, 7i, 7k, 7r, 21, 23 and 29a b showed a potent inhibitory activity toward fatty-acid and sterol biosyntheses. Their IC(50)s were 4.4-6.8 x 10(-6) M and 6.6-9.8 x 10(-6) M, respectively. These activities were always superior to those of compounds I, II, III and Clinofibrate as references. The inhibitory activity toward the sterol biosynthesis of these compounds was inferior to that of Pravastatin. The reducing effects of the representative compounds (7e and 7l) toward plasma cholesterols and triglyceride were evaluated in Japanese white rabbits (30 and 100 mg/kg, po) and compared with those of Clinofibrate:and Pravastatin; The compounds showed a similar hypocholesterolemic effect to Pravastatin and a more potent hypotriglycemic effect than Clinofibrate and Pravastatin in this animal model. Thus, a dual,action of hypolipidemic effects was noted in 7e and 7l compared with the references.

  DOI：

  10.1016/0223-5234(94)90029-9
• 作为产物：
  描述：

  1-(4-chlorophenyl)-5-oxopyrrolidine-3-carboxylic acid methyl ester 在 甲醇 、 sodium tetrahydroborate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 1-(4-chlorophenyl)-4-cyanomethyl-2-oxo-pyrrolidine
  参考文献：
  名称：

  Synthesis of 4-[1-(substituted phenyl)-2-oxo-pyrrolidin-4-yl]methyloxybenzoic acids and related compounds, and their inhibitory capacities toward fatty-acid and sterol biosyntheses

  摘要：

  The synthesis of a series of 4[1-(substituted phenyl)-2-oxo-pyrrolidin-4-yl]methyloxybenzoic acids and related compounds, and their evaluation for inhibitory capacity toward fatty-acid and sterol biosyntheses using rats' liver slices in vitro and rabbits in vivo, are described. Among the compounds synthesized, 7e, 7g, 7h, 7i, 7k, 7r, 21, 23 and 29a b showed a potent inhibitory activity toward fatty-acid and sterol biosyntheses. Their IC(50)s were 4.4-6.8 x 10(-6) M and 6.6-9.8 x 10(-6) M, respectively. These activities were always superior to those of compounds I, II, III and Clinofibrate as references. The inhibitory activity toward the sterol biosynthesis of these compounds was inferior to that of Pravastatin. The reducing effects of the representative compounds (7e and 7l) toward plasma cholesterols and triglyceride were evaluated in Japanese white rabbits (30 and 100 mg/kg, po) and compared with those of Clinofibrate:and Pravastatin; The compounds showed a similar hypocholesterolemic effect to Pravastatin and a more potent hypotriglycemic effect than Clinofibrate and Pravastatin in this animal model. Thus, a dual,action of hypolipidemic effects was noted in 7e and 7l compared with the references.

  DOI：

  10.1016/0223-5234(94)90029-9

文献信息

• Phenylcarboxylic acid derivatives having hetero ring
  申请人：Otsuka Pharmaceutical Company, Limited

  公开号：US05145865A1

  公开（公告）日：1992-09-08

  Phenylcarboxylic acid derivatives having a hetero ring in the substituent of the formula: ##STR1## wherein R.sup.1 is halogen, alkyl, cycloalkyl, hydroxy, alkoxy, phenoxy which has a substituent selected from halogen and alkyl, carboxyl, alkylsulfonyloxy, phenylsulfonyloxy optionally substituted by halogen, alkylsulfonyloxyalkoxy, amino, alkanoylamino, benzoylamino, alkenyloxy, phenylalkoxyalkoxy, hydroxyalkoxy, phenylalkoxy having optionally 1 to 3 substituents selected from halogen, alkyl and alkoxy, halogenoalkyl, cycloalkyloxy optionally substituted by hydroxy, alkoxy substituted by cycloalkyl having optionally hydroxy substituent, imidazolylalkyl or imidazolylalkoxy; k is 0 or 1 to 3; or (R.sup.1).sub.k is alkylenedioxy; A is alkylene or alkylenoxy; l is 0 or 1; B is methylene or carbonyl; m is 0 or 1; D is alkylene; E is alkylene or alkenylene; n is 0 or 1; and R.sup.2 is hydrogen or alkyl, or a salt thereof, which have fatty acid synthesis-inhibitory activity, cholesterol synthesis-inhibitory activity and are useful as antilipidemic agent, prophylactic and treating agent of arteriosclerosis, prophylactic and treating agent of obesity, antidiabetics.

  具有杂环取代基的苯甲酸衍生物的化学式：其中R.sup.1是卤素、烷基、环烷基、羟基、烷氧基、苯氧基，其取代基可选择自卤素和烷基、羧基、烷基磺酰氧基、苯基磺酰氧基，可选择地取代为卤素、烷基磺酰氧基烷氧基、氨基、烷酰胺基、苯甲酰胺基、烯烃氧基、苯基烷氧基烷氧基、羟基烷氧基、苯基烷氧基，其可选择地具有1至3个取代基，选自卤素、烷基和烷氧基、卤代烷基、环烷氧基，可选择地取代为羟基，烷氧基取代为环烷基，其可选择地具有羟基取代基，咪唑基烷基或咪唑基烷氧基；k为0或1至3；或（R.sup.1）.sub.k为亚烷二氧基；A为烷基或烷氧基；l为0或1；B为亚甲基或羰基；m为0或1；D为烷基；E为烷基或烯基；n为0或1；R.sup.2为氢或烷基，或其盐，具有脂肪酸合成抑制活性、胆固醇合成抑制活性并用作抗血脂药物、动脉粥样硬化的预防和治疗药物、肥胖症的预防和治疗药物、抗糖尿病药物。
• Lp(a)-LOWERING AGENTS AND APOPROTEIN (a) PRODUCTION INHIBTORS
  申请人：TAIHO PHARMACEUTICAL COMPANY, LIMITED

  公开号：EP1000620A1

  公开（公告）日：2000-05-17

  Lp(a)-lowering agents or apo(a) production inhibitors containing as the active ingredient phenylcarboxylic acid derivatives represented by general formula (1) or salts thereof, wherein R1 represents optionally substituted phenyl; A represents lower alkylene or lower alkyleneoxy; B represents methylene or carbonyl; D represents lower alkylene; E represents lower alkylene or lower alkenylene; R2 represents hydrogen or lower alkyl; and l, m and n are each 0 or 1. These drugs can significantly lower Lp(a) while scarcely showing any side effects.

  Lp(a)降低剂或apo(a)生成抑制剂，其活性成分为通式(1)代表的苯基羧酸衍生物或其盐类，其中R1代表任选取代的苯基；A代表低级亚烷基或低级亚烷氧基；B代表亚甲基或羰基；D代表低级亚烷基；E代表低级亚烷基或低级亚烯基；R2代表氢或低级亚烷基；l、m和n均为0或1。这些药物可以大大降低脂蛋白（a），同时几乎没有任何副作用。
• Phenylcarboxylic acid derivatives having a hetero ring
  申请人：OTSUKA PHARMACEUTICAL CO., LTD.

  公开号：EP0393607B1

  公开（公告）日：1996-02-21
• Lp(a)-LOWERING AGENTS AND APOPROTEIN (a) PRODUCTION INHIBITORS
  申请人：TAIHO PHARMACEUTICAL COMPANY, LIMITED

  公开号：EP1000620B1

  公开（公告）日：2005-12-07
• US5145865A
  申请人：——

  公开号：US5145865A

  公开（公告）日：1992-09-08