1-(4-Tolyl)-4-hydroxymethyl-2-pyrrolidone | 133747-59-8

• 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-Tolyl)-4-hydroxymethyl-2-pyrrolidone
• 英文别名: 4-(hydroxymethyl)-1-(4-methylphenyl)pyrrolidin-2-one
• CAS: 133747-59-8
• 化学式: C₁₂H₁₅NO₂
• 分子量: 205.257
• InChiKey: AZLGRTUOZKHRSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(4-Tolyl)-4-hydroxymethyl-2-pyrrolidone 在 氢氧化钾 、 potassium carbonate 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-[1-(4-Tolyl)-2-pyrrolidon-4-yl]methoxybenzoic acid
  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：

  5-氧代-1-(4-甲苯)吡咯烷-3-羧酸 在 sodium tetrahydroborate 、 氯化亚砜 作用下， 以 乙醇 为溶剂， 反应 5.5h， 生成 1-(4-Tolyl)-4-hydroxymethyl-2-pyrrolidone
  参考文献：
  名称：

  A 2B腺苷受体拮抗剂：新型黄嘌呤衍生物的设计，合成和生物学评估

  摘要：

  甲2BA Dor是低亲和力腺苷受体，通过GS功能介导的cAMP的升高和随后的下游信号传导。该受体与肺炎性疾病如COPD和哮喘有关。在文献中已经报道了几种有效的和选择性的A 2B AdoR拮抗剂，但是大多数化合物的药代动力学特性较差。因此，为了鉴定具有改善的药代动力学特性的新颖，有效和选择性的A 2B AdoR拮抗剂，我们首先探索了更受约束的MRS-1754形式（4）。为了改善代谢稳定性，尝试了几种接头修饰，以取代黄嘌呤头基的C8位和末端苯环之间的酰胺接头以及不同的苯基或其他杂芳基。SAR优化导致鉴定了两种新型A 2B AdoR拮抗剂，即8- {1- [5-Oxo-1-（4-三氟甲基-苯基）-吡咯烷-3-基甲基] -1H-吡唑-4-基} -1 ，3-二丙基-黄嘌呤（31）和8-（1- {2-氧代-2- [4-（3-三氟甲基-苯基）-哌嗪-1-基]-乙基} -1H-吡唑-4-基）-1,3-二丙

  DOI：

  10.1016/j.ejmech.2016.11.007

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。
• 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
• US5145865A
  申请人：——

  公开号：US5145865A

  公开（公告）日：1992-09-08
• A 2B adenosine receptor antagonists: Design, synthesis and biological evaluation of novel xanthine derivatives
  作者：Sujay Basu、Dinesh A. Barawkar、Vidya Ramdas、Yogesh Waman、Meena Patel、Anil Panmand、Santosh Kumar、Sachin Thorat、Rajesh Bonagiri、Dilip Jadhav、Partha Mukhopadhyay、Vandna Prasad、B. Srinivasa Reddy、Arnab Goswami、Sandhya Chaturvedi、Suraj Menon、Azfar Quraishi、Indraneel Ghosh、Sushant Dusange、Shalini Paliwal、Abhay Kulkarni、Vikas Karande、Rhishikesh Thakre、Gaurav Bedse、Sreekanth Rouduri、Jayasagar Gundu、Venkata P. Palle、Anita Chugh、Kasim A. Mookhtiar

  DOI：10.1016/j.ejmech.2016.11.007

  日期：2017.2

  affinity adenosine receptor that functions by Gs mediated elevation of cAMP and subsequent downstream signaling. The receptor has been implicated in lung inflammatory disorders like COPD and asthma. Several potent and selective A2BAdoR antagonists have been reported in literature, however most of the compounds suffer from poor pharmacokinetic profile. Therefore, with the aim to identify novel, potent and

  甲2BA Dor是低亲和力腺苷受体，通过GS功能介导的cAMP的升高和随后的下游信号传导。该受体与肺炎性疾病如COPD和哮喘有关。在文献中已经报道了几种有效的和选择性的A 2B AdoR拮抗剂，但是大多数化合物的药代动力学特性较差。因此，为了鉴定具有改善的药代动力学特性的新颖，有效和选择性的A 2B AdoR拮抗剂，我们首先探索了更受约束的MRS-1754形式（4）。为了改善代谢稳定性，尝试了几种接头修饰，以取代黄嘌呤头基的C8位和末端苯环之间的酰胺接头以及不同的苯基或其他杂芳基。SAR优化导致鉴定了两种新型A 2B AdoR拮抗剂，即8- 1- [5-Oxo-1-（4-三氟甲基-苯基）-吡咯烷-3-基甲基] -1H-吡唑-4-基} -1 ，3-二丙基-黄嘌呤（31）和8-（1- 2-氧代-2- [4-（3-三氟甲基-苯基）-哌嗪-1-基]-乙基} -1H-吡唑-4-基）-1,3-二丙
• 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
  作者：S Watanabe、K Ogawa、T Ohmo、S Yano、H Yamada、T Shirasaka

  DOI：10.1016/0223-5234(94)90029-9

  日期：1994.1

  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.