5-氧代-1-(2-苯基乙基)吡咯烷-3-羧酸 | 30380-70-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: 5-氧代-1-(2-苯基乙基)吡咯烷-3-羧酸
• 英文名称: (+/-)-1-Phenethyl-5-oxo-pyrrolidin-3-carbonsaeure
• 英文别名: 5-oxo-1-phenethylpyrrolidine-3-carboxylic acid；5-Oxo-1-phenaethyl-pyrrolidin-3-carbonsaeure；5-oxo-1-phenethyl-3-pyrrolidinecarboxylic acid；5-Oxo-1-(2-phenylethyl)pyrrolidine-3-carboxylic acid
• CAS: 30380-70-2
• 化学式: C₁₃H₁₅NO₃
• mdl: MFCD00973748
• 分子量: 233.267
• InChiKey: WXPXDXDHJYRETJ-UHFFFAOYSA-N

物化性质

• 熔点：
  192-193 °C
• 沸点：
  471.1±45.0 °C(Predicted)
• 密度：
  1.248±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.384
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  5-氧代-1-(2-苯基乙基)吡咯烷-3-羧酸 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成 N-[3-(4-benzylpiperidin-1-yl)propyl]-5-oxo-N-phenyl-1-(2-phenylethyl)pyrrolidine-3-carboxamide
  参考文献：
  名称：

  CCR5 Antagonists as Anti-HIV-1 Agents. 1. Synthesis and Biological Evaluation of 5-Oxopyrrolidine-3-carboxamide Derivatives

  摘要：

  一种新型的铅化合物N-{3-[4-(4-氟苯甲酰)piperidin-1-基]丙基}-1-甲基-5-氧代-N-苯基吡咯烷-3-羧酰胺（1）通过高通量筛选与[125I]RANTES和CCR5表达的CHO细胞被鉴定为CCR5拮抗剂。化合物1的IC50值为1.9 μM。为了提高化合物1的结合亲和力，合成了一系列5-氧代吡咯烷-3-羧酰胺。向中心苯环引入3,4-二氯取代基（10i，IC50=0.057 μM；11b，IC50=0.050 μM）或用1-苄基取代5-氧代吡咯烷部分的1-甲基基团（12e，IC50=0.038 μM）被发现有效提高了对CCR5的亲和力。化合物10i、11b和12e也分别以0.44、0.19和0.49 μM的IC50值抑制了CCR5使用的HIV-1包膜介导的膜融合。

  DOI：

  10.1248/cpb.52.63
• 作为产物：
  描述：

  衣康酸二甲酯 在 水 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 生成 5-氧代-1-(2-苯基乙基)吡咯烷-3-羧酸
  参考文献：
  名称：

  Inhibition of noroviruses by piperazine derivatives

  摘要：

  There is currently an unmet need for the development of small-molecule therapeutics for norovirus infection. The piperazine scaffold, a privileged structure embodied in many pharmacological agents, was used to synthesize an array of structurally-diverse derivatives which were screened for anti-norovius activity in a cell-based replicon system. The studies described herein demonstrate for the first time that functionalized piperazine derivatives possess anti-norovirus activity. Furthermore, these studies have led to the identification of two promising compounds (6a and 9I) that can be used as a launching pad for the optimization of potency, cytotoxicity, and drug-like characteristics. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.122

文献信息

• Discovery and Characterization of the First Nonpeptide Antagonists for the Relaxin-3/RXFP3 System
  作者：Elaine A. Gay、Dongliang Guan、Kalynn Van Voorhies、Vineetha Vasukuttan、Kelly M. Mathews、Joyce Besheer、Chunyang Jin

  DOI：10.1021/acs.jmedchem.2c00508

  日期：2022.6.9

  processes such as stress responses, appetite control, and motivation for reward. To date, pharmacological studies of RXFP3 have been limited to peptide ligands. In this study, we report the discovery of the first small-molecule antagonists of RXFP3 through a high-throughput screening campaign. Focused structure–activity relationship studies of the hit compound resulted in RLX-33 (33) that was able to

  神经肽松弛素 3/RXFP3 系统参与许多重要的生理过程，例如应激反应、食欲控制和奖赏动机。迄今为止，RXFP3 的药理学研究仅限于肽配体。在这项研究中，我们报告了通过高通量筛选活动发现的第一个 RXFP3 小分子拮抗剂。对命中化合物的集中构效关系研究导致 RLX-33 ( 33) 能够在一系列功能测定中抑制松弛素 3 的活性。RLX-33 对 RXFP3 的选择性高于松弛素/胰岛素超家族中的两个相关成员 RXFP1 和 RXFP4，并且具有用于行为评估的有利药代动力学特性。当对大鼠进行腹膜内给药时，RLX-33 可阻断由 RXFP3 选择性激动剂 R3/I5 诱导的食物摄入。总的来说，我们的研究结果表明，RLX-33 代表了一种有前途的拮抗剂支架，可用于开发靶向松弛素 3/RXFP3 系统的药物。
• CYCLIC AMIDE COMPOUNDS, PROCESS FOR THE PREPARATION OF THE SAME AND USES THEREOF
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1180513A1

  公开（公告）日：2002-02-20

  A compound of the formula: wherein R1 is a hydrocarbon group, R2 is a hydrocarbon group having 2 or more carbon atoms, where R1 and R2 may in combination form, together with an adjacent nitrogen atom, a ring optionally having a substituent or substituents, R3 is a hydrocarbon group optionally having a substituent or substituents or a heterocyclic group optionally having a substituent or substituents, R4 is a hydrogen atom, a hydrocarbon group, a heterocyclic group and the like, E is a divalent chain hydrocarbon group and the like, G is CO or SO2, J is a nitrogen atom, a methine group and the like, and Q and R are each a divalent chain C1-3 hydrocarbon group and the like, and a salt thereof show a superior CCR5 antagonistic activity and are useful as agents for the prophylaxis or treatment of HIV infection of human peripheral blood mononuclear cells, particularly AIDS.

  以下式子的化合物 其中 R1 是烃基；R2 是具有 2 个或 2 个以上碳原子的烃基；其中 R1 和 R2 可与相邻的氮原子结合形成任选具有一个或多个取代基的环；R3 是任选具有一个或多个取代基的烃基或任选具有一个或多个取代基的杂环基；R4 是氢原子、烃基、杂环基等；E 是二价链烃基等；G 是 CO 或 SO2；J 是氮原子、甲基等、E是二价链烃基等，G是CO或SO2，J是氮原子、甲基等，Q和R各自是二价链C1-3烃基等，它们及其盐具有优异的CCR5拮抗活性，可作为预防或治疗人类外周血单核细胞HIV感染，特别是艾滋病的药物。
• OPTICALLY ACTIVE 3-AMINOPYRROLIDINE SALT, PROCESS FOR PRODUCTION THEREOF, AND METHOD FOR OPTICAL RESOLUTION OF 3-AMINOPYRROLIDINE
  申请人：Toray Fine Chemicals Co., Ltd.

  公开号：EP2236496A1

  公开（公告）日：2010-10-06

  Disclosed are an optically active 3-aminopyrrolidine (3AP) salt having a high optical purity which is useful as an intermediate in an industrial production method of an optically active 3AP, an efficient method for producing it, and an efficient industrial method for optical resolution of 3AP. Optical resolution of 3AP is efficiently carried out by reacting racemic 3AP with optically active 2-methoxyphenylacetic acid in the presence of a mineral acid such as hydrochloric acid in an aqueous solvent, followed by separation of the resulting diastereomer salt constituted by 1 mole of optically active 3AP and 2 moles of optically active 2-methoxyphenylacetic acid.

  本发明公开了一种具有高光学纯度的光学活性 3-氨基吡咯烷（3AP）盐，该盐可用作光学活性 3AP 工业生产方法的中间体，还公开了一种生产该盐的高效方法，以及一种对 3AP 进行光学解析的高效工业方法。外消旋 3AP 与具有光学活性的 2-甲氧基苯乙酸在矿物酸（如盐酸）存在下于水性溶剂中反应，然后分离由 1 摩尔具有光学活性的 3AP 和 2 摩尔具有光学活性的 2-甲氧基苯乙酸构成的非对映异构盐，可有效地进行 3AP 的光学解析。
• Pyrrolidone carboxamides
  申请人：Isler Markus

  公开号：US20050192292A1

  公开（公告）日：2005-09-01

  Pyrrolidone carboxamides of formula (I) where R 2 =a group of formula (a) or (b), R 5 =phenyl, heteroalkyl, aryloxy, alkoxy, alkanoyl or —NR 6 R 7 and R 1 , X, R 3 , R 4 , R 6 and R 7 have the meanings given in the description and the claims, pharmaceutically applicable acid addition salts with basic compounds of formula (I), pharmaceutically applicable salts of acid compounds of formula (I) with bases, pharmaceutically applicable esters of hydroxy- or carboxy-group containing compounds of formula (I) and hydrates and solvates thereof, inhibit the interaction of neuropeptide Y (NPY) with one of the neuropeptide receptor subtypes (NPY-Y5) and are particularly suitable for the prevention and treatment of arthritis, diabetes and especially eating disorders and obesity. The above can be produced by known methods and converted into a galenic dosage form.

  式 (I) 的吡咯烷酮羧酰胺，其中 R 2 =式 (a) 或 (b) 的基团，R 5 =苯基、杂烷基、芳氧基、烷氧基、烷酰基或-NR 6 R 7 和 R 1 ，X，R 3 , R 4 , R 6 和 R 7 具有在说明书和权利要求书中给出的含义；式(I)碱性化合物的药学上适用的酸加成盐；式(I)酸性化合物与碱的药学上适用的盐；含羟基或羧基的式(I)化合物的药学上适用的酯及其水合物和溶剂、抑制神经肽 Y（NPY）与一种神经肽受体亚型（NPY-Y5）的相互作用，特别适用于预防和治疗关节炎、糖尿病，尤其是进食障碍和肥胖症。上述药物可通过已知方法生产，并转化为半成品剂型。
• 10.1021/acs.jmedchem.4c00320
  作者：Zhang, Laiying、Yang, Jiaxing、Xu, Xin、Zhang, Jiangnan、Qiu, Zhiqiang、Ju, Yuan、Luo, Baozhu、Liu, Yan、Gou, Xupeng、Sui, Jing、Chen, Baoyi、Wang, Yanmei、Tao, Tao、He, Lei、Yang, Tao、Luo, Youfu

  DOI：10.1021/acs.jmedchem.4c00320

  日期：——

  Staphylococcus aureus enoyl-acyl carrier protein reductase (SaFabI) emerges as a compelling target for combating methicillin-resistant S. aureus (MRSA) infections. Herein, compound 1, featuring a 4-(1H-benzo[d]imidazol-2-yl)pyrrolidin-2-one scaffold, was identified as a potent SaFabI inhibitor (IC50 = 976.8 nM) from an in-house library. Subsequent optimization yielded compound n31, with improved inhibitory efficacy

  作为脂肪酸生物合成中的限速酶，金黄色葡萄球菌烯酰酰基载体蛋白还原酶 ( Sa FabI)​​ 成为对抗耐甲氧西林金黄色葡萄球菌(MRSA) 感染的引人注目的靶标。在此，以 4-(1 H-苯并[ d ]咪唑-2-基)吡咯烷-2-酮支架为特征的化合物1被内部鉴定为有效的Sa FabI 抑制剂 (IC 50 = 976.8 nM)图书馆。随后的优化产生了化合物n31 ，其对酶活性的抑制功效（IC 50 = 174.2 nM）和对金黄色葡萄球菌的选择性效力（MIC = 1–2 μg/mL）得到改善。从机制上讲， n31在细胞环境中直接抑制Sa FabI。此外， n31表现出良好的安全性和药代动力学特征，并且可以剂量依赖性地治疗 MRSA 引起的皮肤感染，其效果优于已批准的药物利奈唑胺。 n31的手性分离产生( S )-n31 ，具有优异的活性（IC 50 = 94.0 nM，MIC = 0.25–1