1-benzyl-5-oxo-2-phenylpyrrolidine-3-carboxylic acid | 94655-24-0

• 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-benzyl-5-oxo-2-phenylpyrrolidine-3-carboxylic acid
• 英文别名: 1-N-BENZYL-4-CARBOXY-5-PHENYL-PYRROLIDIN-2-ONE
• CAS: 94655-24-0
• 化学式: C₁₈H₁₇NO₃
• mdl: MFCD03306014
• 分子量: 295.338
• InChiKey: DKXRDFRRCPUUKU-UHFFFAOYSA-N

物化性质

• 熔点：
  169-171 °C
• 沸点：
  552.4±50.0 °C(Predicted)
• 密度：
  1.278±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-benzyl-5-oxo-2-phenylpyrrolidine-3-carboxylic acid 在 1,3-二碘-5,5-二甲基海因 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  使用1,3-二碘-5,5-二甲基乙内酰脲通过对锥酸和β-羧基 -γ-丁内酰胺的脱羧碘化，方便地合成α，β-不饱和γ-丁内酯和γ-丁内酰胺†

  摘要：

  开发了一种简便的合成方法，合成α，β-不饱和γ-丁内酯和α，β-不饱和γ-丁内酰胺。该反应通过在辐射下使用1,3-二碘-5,5-二甲基乙内酰脲（DIH）对对苯二甲酸和β-羧基-γ-丁内酰胺进行脱羧碘化，然后对β-碘-γ-丁内酯和γ-进行加氢碘化来进行。丁内酰胺可提供高产率的α，β-不饱和γ-丁内酯和γ-丁内酰胺，它们是有机合成中合成有用的组成部分。

  DOI：

  10.1039/c5ob01574j
• 作为产物：
  描述：

  (E)-N-benzylidenebenzylamine 生成 1-benzyl-5-oxo-2-phenylpyrrolidine-3-carboxylic acid
  参考文献：
  名称：

  SHETTY, BOLA V.;MCFADDEN, ARTHUR;HOFER, PETER

  摘要：

  DOI：

文献信息

• Analgesic 4-carboxy-pyrrolidin-2-one compound
  申请人：The Purdue Frederick Company

  公开号：US04476311A1

  公开（公告）日：1984-10-09

  Analgesic and anti-inflammatory compounds are provided. These compounds possess the following general formula: ##STR1## wherein R=--COOR.sub.5, --CH.sub.2 CO.sub.2 H, ##STR2## wherein A and B=hydrogen, lower alkyl, hydroxy alkyl, lower alkyl amine, substituted lower alkyl amine, aminoalkyl, substituted aminoalkyl; R.sub.5 =lower alkyl; R.sub.1 =aryl, substituted aryl, aralkyl, alkyl, hydrogen, substituted aralkyl and heterocycle; R.sub.2 =aryl, substituted aryl, aralkyl, alkyl, substituted aralkyl, heterocycle, substituted heterocycle, biphenyl, substituted biphenyl, naphthyl, and substituted naphthyl; R.sub.3 =aryl, substituted aryl, hydrogen, aralkyl, substituted aralkyl, alkyl, heterocycle and substituted heterocycle; R.sub.2 and R.sub.3 together form a ring; R.sub.4 =hydrogen, phenyl, substituted phenyl, heterocycle; alkyl, substituted alkyl; or, R.sub.1 and R.sub.4 may form a ring; X=>C.dbd.O, --CH.sub.2 --; Y=--S--CHR.sub.4 --, --O--OHR.sub.4 --, --CHR.sub.4 --, --CR.sub.6 R.sub.7 --CHR.sub.4 --, ##STR3## wherein R.sub.6 =same as R.sub.4 ; R.sub.7 =same as R.sub.4 ; R.sub.6 and R.sub.7 may form a ring; and Z=hydrogen, halogen, alkyl, substituted alkyl, hydroxy, alkyloxy, amino, substituted amino, nitro, aryl, substituted aryl, aryloxy.

  提供镇痛和抗炎化合物。这些化合物具有以下一般公式：##STR1## 其中 R=--COOR.sub.5, --CH.sub.2 CO.sub.2 H, ##STR2## 其中 A 和 B=氢，较低烷基，羟基烷基，较低烷基胺，取代的较低烷基胺，氨基烷基，取代的氨基烷基；R.sub.5=较低烷基；R.sub.1=芳基，取代的芳基，芳基烷基，烷基，氢，取代的芳基烷基和杂环；R.sub.2=芳基，取代的芳基，芳基烷基，烷基，取代的芳基烷基，杂环，取代的杂环，联苯，取代的联苯，萘基，取代的萘基；R.sub.3=芳基，取代的芳基，氢，芳基烷基，取代的芳基烷基，烷基，杂环和取代的杂环；R.sub.2 和 R.sub.3 可以一起形成一个环；R.sub.4=氢，苯基，取代的苯基，杂环；烷基，取代的烷基；或者，R.sub.1 和 R.sub.4 可以形成一个环；X=>C.dbd.O，--CH.sub.2--; Y=--S--CHR.sub.4 --，--O--OHR.sub.4 --，--CHR.sub.4 --，--CR.sub.6 R.sub.7 --CHR.sub.4 --，##STR3## 其中 R.sub.6=与 R.sub.4 相同；R.sub.7=与 R.sub.4 相同；R.sub.6 和 R.sub.7 可以形成一个环；Z=氢，卤素，烷基，取代的烷基，羟基，烷氧基，氨基，取代的氨基，硝基，芳基，取代的芳基，芳氧基。
• Site-Specific Synthesis of β-Fluorinated γ-Butyrolactams via Decarboxylative Fluorination of β-Carboxyl-γ-Butyrolactams
  作者：Supasorn Phae-nok、Manat Pohmakotr、Chutima Kuhakarn、Vichai Reutrakul、Darunee Soorukram

  DOI：10.1002/ejoc.201900685

  日期：2019.8.7

  The direct and site‐specific synthesis of β‐fluorinated γ‐butyrolactams via AgNO3 mediated decarboxylative fluorination of β‐carboxyl‐γ‐butyrolactams using Selectfluor® as a fluorine source was described. The β‐fluorinated γ‐butyrolactams including chiral derivatives were obtained in moderate to good yields.

  描述了使用Selectfluor®作为氟源，通过AgNO 3介导的β-羧基-γ-丁内酰胺的直接脱羧氟化反应，直接合成β-氟化的γ-丁内酰胺。包括手性衍生物在内的β-氟化γ-丁内酰胺的收率中等至良好。
• 1-substituted, 2,3-diphenyl-3-hydroxymethyl pyrrolidines, where the 2-
  申请人：The Purdue Frederick Company

  公开号：US04731457A1

  公开（公告）日：1988-03-15

  Analgesic and anti-inflamatory compounds of the formula ##STR1## wherein n=0-1, X=Halo, lower Alkoxy, HO--, Lower Alkyl, and R= ##STR2##

  镇痛和抗炎化合物的公式为 ##STR1## 其中n = 0-1，X = 卤素，低烷氧基，HO--，低烷基，R = ##STR2##
• Analgesic and anti-inflammatory compounds
  申请人：The Purdue Frederick Company

  公开号：US04639529A1

  公开（公告）日：1987-01-27

  Analgesic and anti-inflammatory compounds are provided. These compounds possess the following general formula: ##STR1## wherein R=--COOR.sub.5, --CH.sub.2 CO.sub.2 H, ##STR2## wherein A and B=hydrogen, lower alkyl, hydroxy alkyl, lower alkyl amine, substituted lower alkyl amine, aminoalkyl, substituted aminoalkyl; R.sub.5 =lower alkyl; R.sub.1 =aryl, substituted aryl, aralkyl, alkyl, hydrogen, substituted aralkyl and heterocycle; R.sub.2 =aryl, substituted aryl, aralkyl, alkyl, substituted aralkyl, heterocycle, substituted heterocycle, biphenyl, substituted biphenyl, naphthyl, and substituted naphthyl; R.sub.3 =aryl, substituted aryl, hydrogen, aralkyl, substituted aralkyl, alkyl, heterocycle and substituted heterocycle; R.sub.2 and R.sub.3 together form a ring; R.sub.4 =hydrogen, phenyl, substituted phenyl, heterocycle; alkyl, substituted alkyl; or, R.sub.1 and R.sub.4 may form a ring; ##STR3## --CH.sub.2 --; Y=--S--CHR.sub.4 --, --O--OHR.sub.4 --,--CHR.sub.4 --, --CR.sub.6 R.sub.7 --CHR.sub.4, ##STR4## wherein R.sub.6 =same as R.sub.4 ; R.sub.7 =same as R.sub.4 ; R.sub.6 and R.sub.7 may form a ring; and Z=hydrogen, halogen, alkyl, substituted alkyl, hydroxy, alkyloxy, amino, substituted amino, nitro, aryl, substituted aryl, aryloxy.

  提供了镇痛和抗炎化合物。这些化合物具有以下一般式：##STR1##其中R=--COOR.sub.5，--CH.sub.2 CO.sub.2 H，##STR2##其中A和B=氢，低烷基，羟基烷基，低烷基胺，取代低烷基胺，氨基烷基，取代氨基烷基；R.sub.5=低烷基；R.sub.1=芳基，取代芳基，芳基烷基，烷基，氢，取代芳基烷基和杂环；R.sub.2=芳基，取代芳基，芳基烷基，烷基，取代芳基烷基，杂环，取代杂环，联苯，取代联苯，萘基和取代萘基；R.sub.3=芳基，取代芳基，氢，芳基烷基，取代芳基烷基，烷基，杂环和取代杂环；R.sub.2和R.sub.3一起形成环；R.sub.4=氢，苯基，取代苯基，杂环；烷基，取代烷基；或者，R.sub.1和R.sub.4可以形成环；##STR3##--CH.sub.2 --；Y=--S--CHR.sub.4 --，--O--OHR.sub.4 --，--CHR.sub.4 --，--CR.sub.6 R.sub.7 --CHR.sub.4，##STR4##其中R.sub.6=与R.sub.4相同；R.sub.7=与R.sub.4相同；R.sub.6和R.sub.7可以形成环；Z=氢，卤素，烷基，取代烷基，羟基，烷氧基，氨基，取代氨基，硝基，芳基，取代芳基，芳氧基。
• From Nature to Synthetic Compounds: Novel 1(N),2,3 Trisubstituted-5-oxopyrrolidines Targeting Multiple Myeloma Cells
  作者：Roberta Listro、Alessio Malacrida、Francesca Alessandra Ambrosio、Giacomo Rossino、Marcello Di Giacomo、Valeria Cavalloro、Martina Garbagnoli、Pasquale Linciano、Daniela Rossi、Guido Cavaletti、Giosuè Costa、Stefano Alcaro、Mariarosaria Miloso、Simona Collina

  DOI：10.3390/ijms232113061

  日期：——

  The insurgence of drug resistance in treating Multiple Myeloma (MM) still represents a major hamper in finding effective treatments, although over the past decades new classes of drugs, such as proteasome inhibitors and immunomodulatory drugs, have been discovered. Recently, our research team, within a Nature-Aided Drug Discovery project, isolated from Hibiscus Sabdariffa L. calyces the secondary metabolite called Hib-ester which possesses antiproliferative properties against human multiple myeloma RPMI 8226 cells, reduces migration and cell invasion and inhibits proteasome without neurotoxic effects. In the present study, we explored the chemical spaces of the hit compound Hib-ester. We explored the structure-activity relationships (SAR), and we optimized the scaffold through sequentially modifying Hib-ester subunits. Compound screening was performed based on cytotoxicity against the RPMI 8226 cells to assess the potential efficacy toward human MM. The ability of the most effective molecules to inhibit the proteasome was evaluated and the binding mode of the most promising compounds in the proteasome chymotrypsin binding pocket was deciphered through molecular modeling simulations. Compounds 13 and 14 are more potent than Hib-ester, demonstrating that our strategy was suitable for the identification of a novel chemotype for developing possible drug candidates and hopefully widening the drug armamentarium against MM.

  过去几十年来，虽然蛋白酶体抑制剂和免疫调节药物等新药不断被发现，但治疗多发性骨髓瘤（MM）的抗药性问题仍然是找到有效治疗方法的主要障碍。最近，我们的研究团队在一个自然辅助药物发现项目中，从木槿萼片中分离出了一种名为 Hib-ester 的次级代谢产物，它具有抗人多发性骨髓瘤 RPMI 8226 细胞增殖的特性，能减少细胞迁移和侵袭，并能抑制蛋白酶体，且无神经毒性作用。在本研究中，我们探索了命中化合物 Hib-ester 的化学空间。我们探索了结构-活性关系（SAR），并通过连续修饰 Hib-ester 亚基优化了支架。根据对 RPMI 8226 细胞的细胞毒性进行了化合物筛选，以评估对人类 MM 的潜在疗效。评估了最有效分子抑制蛋白酶体的能力，并通过分子建模模拟破译了最有希望的化合物在蛋白酶体糜蛋白酶结合袋中的结合模式。化合物 13 和 14 比 Hib-ester 更有效，这表明我们的策略适用于鉴定新的化学类型，以开发可能的候选药物，并有望扩大抗 MM 的药物范围。