(S)-methyl 2-((tert-butoxycarbonyl)amino)-5-(2-chlorophenyl)-5-oxopentanoate

• 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: (S)-methyl 2-((tert-butoxycarbonyl)amino)-5-(2-chlorophenyl)-5-oxopentanoate
• 英文别名: methyl (2S)-5-(2-chlorophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoate
• 化学式: C₁₇H₂₂ClNO₅
• 分子量: 355.818
• InChiKey: UHBGIEAIGVXACA-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-methyl 2-((tert-butoxycarbonyl)amino)-5-(2-chlorophenyl)-5-oxopentanoate 在 水 、 三乙酰氧基硼氢化钠 、 三乙胺 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 5.0h， 生成 (2S,5R)-5-(2-chlorophenyl)-1-(2'-methoxy-[1,1'-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  [EN] COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING INFLAMMATORY DISEASES
  [FR] COMPOSÉS, COMPOSITION PHARMACEUTIQUE ET MÉTHODES À UTILISER DANS LE TRAITEMENT DE MALADIES INFLAMMATOIRES

  摘要：

  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。

  公开号：

  WO2015078949A1
• 作为产物：
  描述：

  L-焦谷氨酸 在 4-二甲氨基吡啶 、 正丁基锂 、 氯化亚砜 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 0.83h， 生成 (S)-methyl 2-((tert-butoxycarbonyl)amino)-5-(2-chlorophenyl)-5-oxopentanoate
  参考文献：
  名称：

  Discovery of a Potent Thiazolidine Free Fatty Acid Receptor 2 Agonist with Favorable Pharmacokinetic Properties

  摘要：

  Free fatty acid receptor 2 (FFA2/GPR43) is a receptor for short-chain fatty acids reported to be involved in regulation of metabolism, appetite, fat accumulation, and inflammatory responses and is a potential target for treatment of various inflammatory and metabolic diseases. By bioisosteric replacement of the central pyrrolidine core of a previously disclosed FFA2 agonist with a synthetically more tractable thiazolidine, we were able to rapidly synthesize and screen analogues modified at both the 2- and 3-positions on the thiazolidine core. Herein, we report SAR exploration of thiazolidine FFA2 agonists and the identification of 31 (TUG-1375), a compound with significantly increased potency (7-fold in a cAMP assay) and reduced lipophilicity (50-fold reduced clogP) relative to the pyrrolidine lead structure. The compound has high solubility, high chemical, microsomal, and hepatocyte stability, and favorable pharmacokinetic properties and was confirmed to induce human neutrophil mobilization and to inhibit lipolysis in murine adipocytes.

  DOI：

  10.1021/acs.jmedchem.8b00855

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。
• [EN] SYNTHESIS OF (2S,5R)-5-(2-CHLOROPHENYL)-1-(2'-METHOXY-[1,1'-BIPHENYL]-4-CARBONYL)PYRROLIDINE-2-CARBOXYLIC ACID<br/>[FR] SYNTHÈSE D'ACIDE (2S,5R)-5-(2-CHLOROPHÉNYL)-1-(2'-MÉTHOXY-[1,1'-BIPHÉNYL]-4-CARBONYL)PYRROLIDINE-2-CARBOXYLIQUE
  申请人：EPICS THERAPEUTICS

  公开号：WO2021250174A1

  公开（公告）日：2021-12-16

  The present invention relates to a process of manufacturing of (2S,5R)-5-(2- chlorophenyl)-1-(2'-methoxy-[1,1'-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid (1), including the preparation of (2S,5R)-methyl 5-(2-chlorophenyl)pyrrolidine-2- carboxylate hydrochloride (6.HCl) as intermediate of synthesis:

  本发明涉及一种制备(2S,5R)-5-(2-氯苯基)-1-(2'-甲氧基-[1,1'-联苯]-4-羰基)吡咯烷-2-羧酸（1）的制造过程，包括制备(2S,5R)-甲基5-(2-氯苯基)吡咯烷-2-羧酸酯盐酸盐（6.HCl）作为合成的中间体。
• 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。