N-(4-phenylbutanoyl)-5(R)-tert-butyl-L-proline methyl ester | 725265-92-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(4-phenylbutanoyl)-5(R)-tert-butyl-L-proline methyl ester
• 英文别名: 4-phenylbutanoyl-5(R)-tert-butyl-L-proline methyl ester；methyl (2S,5R)-5-tert-butyl-1-(4-phenylbutanoyl)pyrrolidine-2-carboxylate
• CAS: 725265-92-9
• 化学式: C₂₀H₂₉NO₃
• 分子量: 331.455
• InChiKey: VHTLQGZJSMSREM-DLBZAZTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-phenylbutanoyl)-5(R)-tert-butyl-L-proline methyl ester 在 lithium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 以86%的产率得到N-(4-phenylbutanoyl)-5(R)-tert-butyl-L-proline
  参考文献：
  名称：

  Conformationally rigid N-acyl-5-alkyl-l-prolyl-pyrrolidines as prolyl oligopeptidase inhibitors

  摘要：

  In the N-acyl-(L)-prolyl-pyrrolidine type of prolyl oligopeptidase inhibitors the L-prolyl group was replaced by different 5-alkyl-(L)-prolyl groups, resulting in a series of N-acyl-5-alkyl-(L)-prolyl-pyrrolidines. Since N-amides of 5-alkyl-(L)-prolines are conformationally more rigid than those of (L)-proline, the main objective was to make more rigid prolyl oligopeptidase inhibitors. In the series of compounds where the N-acyl group was a Boc group, the 5(R)-tert-butyl group increased the potency strongly. A similar effect was not observed for the 5(S)-tert-butyl group. In the series of compounds where the N-acyl group was a 4-phenylbutanoyl group, the 5(R)-tert-butyl, 5(R)-methyl and 5(S)-methyl groups did not have an effect on the potency [the 5(S)-tert-butyl group was not tested in this series]. As an additional effect, the 5-tert-butyl groups increased the log P of the compounds 1.5 log units, which might be beneficial when targeting the compounds to the brain. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00363-8
• 作为产物：
  描述：

  4-苯基丁酸 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 N-(4-phenylbutanoyl)-5(R)-tert-butyl-L-proline methyl ester
  参考文献：
  名称：

  Conformationally rigid N-acyl-5-alkyl-l-prolyl-pyrrolidines as prolyl oligopeptidase inhibitors

  摘要：

  In the N-acyl-(L)-prolyl-pyrrolidine type of prolyl oligopeptidase inhibitors the L-prolyl group was replaced by different 5-alkyl-(L)-prolyl groups, resulting in a series of N-acyl-5-alkyl-(L)-prolyl-pyrrolidines. Since N-amides of 5-alkyl-(L)-prolines are conformationally more rigid than those of (L)-proline, the main objective was to make more rigid prolyl oligopeptidase inhibitors. In the series of compounds where the N-acyl group was a Boc group, the 5(R)-tert-butyl group increased the potency strongly. A similar effect was not observed for the 5(S)-tert-butyl group. In the series of compounds where the N-acyl group was a 4-phenylbutanoyl group, the 5(R)-tert-butyl, 5(R)-methyl and 5(S)-methyl groups did not have an effect on the potency [the 5(S)-tert-butyl group was not tested in this series]. As an additional effect, the 5-tert-butyl groups increased the log P of the compounds 1.5 log units, which might be beneficial when targeting the compounds to the brain. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00363-8

文献信息

• [EN] COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING INFLAMMATORY DISEASES<br/>[FR] COMPOSÉS, COMPOSITION PHARMACEUTIQUE ET MÉTHODES À UTILISER DANS LE TRAITEMENT DE MALADIES INFLAMMATOIRES
  申请人：EUROSCREEN SA

  公开号：WO2015078949A1

  公开（公告）日：2015-06-04

  The present invention is directed to compounds of formula (I), useful in treating and/or preventing inflammatory diseases.

  本发明涉及一种化合物，其化学式为(I)，用于治疗和/或预防炎症性疾病。
• [EN] PYRROLIDINE OR THIAZOLIDINE CARBOXYLIC ACID DERIVATIVES, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING METABOLIC DISORDERSAS AS AGONISTS OF G- PROTEIN COUPLED RECEPTOR 43 (GPR43)<br/>[FR] COMPOSÉS, COMPOSITION PHARMACEUTIQUE ET MÉTHODES POUR APPLICATION AU TRAITEMENT DE TROUBLES MÉTABOLIQUES
  申请人：EUROSCREEN SA

  公开号：WO2011073376A1

  公开（公告）日：2011-06-23

  The present invention is directed to novel compounds of formula (I) and their use in treating and/or preventing metabolic diseases.

  本发明涉及具有式（I）的新化合物，以及它们在治疗和/或预防代谢性疾病中的用途。
• Compounds having prolyl oligopeptidase inhibitory activity
  申请人：Gynther Jukka

  公开号：US20060229254A1

  公开（公告）日：2006-10-12

  A compound of formula (I), wherein X, R 1 , R 2 and R 3 are as defined in the disclosure, or a pharmaceutically acceptable salt or ester thereof, useful as a prolyl oligopeptidase inhibitor. The compounds can be used for the treatment of diseases or conditions where prolyl oligopeptidase inhibitors are indicated to be effective, for example for the treatment of neurodegenerative diseases, such as Alzheimer's disease and senile dementia.

  式(I)的化合物，其中X、R1、R2和R3如所披露的定义，或其药学上可接受的盐或酯，可用作脯氨酰寡肽酶抑制剂。这些化合物可用于治疗需要脯氨酰寡肽酶抑制剂具有疗效的疾病或情况，例如用于治疗神经退行性疾病，如阿尔茨海默病和老年性痴呆症。
• PYRROLIDINE OR THIAZOLIDINE CARBOXYLIC ACID DERIVATIVES, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING METABOLIC DISORDERS AS AGONISTS OF G-PROTEIN COUPLED RECEPTOR 43 (GPR43)
  申请人：Hoveyda Hamid R.

  公开号：US20130023539A1

  公开（公告）日：2013-01-24

  The present invention is directed to novel compounds of formula (I) and their use in treating and/or preventing metabolic diseases.

  本发明涉及式（I）的新化合物及其在治疗和/或预防代谢性疾病方面的应用。
• Substituted pyrrolidines as G-protein coupled receptor 43 agonists
  申请人：Ogeda SA

  公开号：US10017468B2

  公开（公告）日：2018-07-10

  The present invention is directed to a process for the preparation of aryl-pyrrolidine carboxylic acid derivative compounds which are useful in treating metabolic diseases, said process consisting of coupling an aryl-pyrrolidine compound with an aryl carboxylic acid compound followed by alkaline or acidic treatment, hydrogenolysis or treatment with a fluoride of the ester intermediate to afford novel aryl-pyrrolidine carboxylic acid derivative compounds.

  本发明涉及一种用于制备治疗代谢性疾病的芳基吡咯烷羧酸衍生物化合物的工艺，所述工艺包括将芳基吡咯烷化合物与芳基羧酸化合物偶联，然后对酯类中间体进行碱性或酸性处理、氢解或用氟化物处理，以得到新型芳基吡咯烷羧酸衍生物化合物。