The chemistry of nitrogen-containing heterocyclic compounds has been a multifaceted area of research for an extended period due to their varied therapeutic and biological significance. N-Aryl pyrrolidine formed by condensation of aryl group with nitrogen atom of pyrrolidine is present in a wide array of compounds. Various significant activities shown by N-arylated pyrrolidine include anti-Alzheimer, antihypoxic, anticancer, plant activator, analgesic effect, and hepatitis C inhibitor. This review summarizes different synthetic approaches, e.g., transition-metal catalyzed and transition-metal-free synthesis, decarboxylation reaction, reductive amination, nucleophilic cyclization, Ullmann-Goldberg amidation, Buchwald-Hartwig reaction, Chan-Evans-Lam coupling, addition to benzyne, multistep reaction, green synthesis, rearrangement reaction, and multicomponent reaction, to afford the derivatives of N-aryl pyrrolidine. It encompasses synthetic strategies documented from 2015 to 2023.

Enhancing the generation of reactive hydroxyl radicals (•OH) is crucial for overcoming the limitations of the low reactivity of heterogeneous Fenton Fe-based catalysts. Researchers have explored various methods to modify catalyst structures to enhance reactivity, yet often at the expense of stability. Herein, suitable carbon and nitrogen-codoped Fe2O3-CuO composites were synthesized via pyrolysis method, demonstrating high Fenton reaction activity and remarkable stability. Experimental findings and density functional theory calculations (DFT) revealed that the presence of oxygen vacancies on the catalyst surface facilitated an increase in exposed FeNC active sites, promoting electron transfer and the accelerating the rate of •OH generation. Moreover, carbon and nitrogen, particularly in the form of pyrrole nitrogen bonded to Fe imparted exceptional stability to the FeNC active sites, mitigating their dissolution. Additionally, the Fe-based catalysts exhibited strong magnetism, enabling easy separation from the reaction solution while maintaining a high degradation efficiency for various organic pollutants, even in the presence of multiple anions. Furthermore, a comprehensive mechanism for methylene blue (MB) degradation was identified, enhancing the potential practical applications of these catalysts.

UNASSIGNED: Despite the progress in comprehending molecular design principles and biochemical processes associated with thrombin inhibition, there is a crucial need to optimize efforts and curtail the recurrence of synthesis-testing cycles. Nitrogen and N-heterocycles are key features of many anti-thrombin drugs. Hence, a pragmatic analysis of nitrogen and N-heterocycles in thrombin inhibitors is important throughout the drug discovery pipeline. In the present work, the authors present an analysis with a specific focus on understanding the occurrence and distribution of nitrogen and selected N-heterocycles in the realm of thrombin inhibitors.
UNASSIGNED: A dataset comprising 4359 thrombin inhibitors is used to scrutinize various categories of nitrogen atoms such as ring, non-ring, aromatic, and non-aromatic. In addition, selected aromatic and aliphatic N-heterocycles have been analyzed.
UNASSIGNED: The analysis indicates that ~62% of thrombin inhibitors possess five or fewer nitrogen atoms. Substituted N-heterocycles have a high occurrence, like pyrrolidine (23.24%), pyridine (20.56%), piperidine (16.10%), thiazole (9.61%), imidazole (7.36%), etc. in thrombin inhibitors.
UNASSIGNED: The majority of active thrombin inhibitors contain nitrogen atoms close to 5 and a combination of N-heterocycles like pyrrolidine, pyridine, piperidine, etc. This analysis provides crucial insights to optimize the transformation of lead compounds into potential anti-thrombin inhibitors.

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Cancer is one of the leading causes of mortality worldwide, making it a public health concern. A novel series of pyrrolidine-carboxamide derivatives 7a-q were developed and examined in a cell viability assay utilizing a human mammary gland epithelial cell line (MCF-10A), where all the compounds exhibited no cytotoxic effects and more than 85% cell viability at a concentration of 50 μM. Antiproliferative activity was evaluated in vitro against four panels of cancer cell lines A-549, MCF-7, Panc-1, and HT-29. Compounds 7e, 7g, 7k, 7n, and 7o were the most active as antiproliferative agents capable of triggering apoptosis. Compound 7g was the most potent of all the derivatives, with a mean IC50 of 0.90 μM compared to IC50 of 1.10 μM for doxorubicin. Compound 7g inhibited A-549 (epithelial cancer cell line), MCF-7 (breast cancer cell line), and HT-29 (colon cancer cell line) more efficiently than doxorubicin. EGFR inhibitory assay results of 7e, 7g, 7k, 7n, and 7o demonstrated that the tested compounds inhibited EGFR with IC50 values ranging from 87 to 107 nM in comparison with the reference drug erlotinib (IC50  = 80 nM). 7e, 7g, 7k, 7n, and 7o inhibited CDK2 efficiently in comparison to the reference dinaciclib (IC50  = 20 nM), with IC50 values ranging from 15 to 31 nM. The results of inhibitory activity assay against different CDK isoforms revealed that the tested compounds had preferential inhibitory activity against the CDK2 isoform.

In bromido-(pyrrolidine-κN)gold(I) bis-(pyrrolidine-κN)gold(I) bromide, [AuBr(pyr)]·[Au(pyr)2]Br (pyr = pyrrolidine, C4H9N), 2, alternating [AuBr(pyr)] mol-ecules and [Au(pyr)2]+ cations are connected by aurophilic contacts to form infinite chains of residues parallel to the b axis. The chains are cross-linked by three N-H⋯Br- hydrogen bonds and an Au⋯Br contact to form a layer structure parallel to the ab plane. Tri-chlorido-(piperidine-κN)gold(III), [AuCl3(pip)] (pip = piperidine, C5H11N), 3, consists of mol-ecules with the expected square-planar coordination at the gold atom, which are connected by an N-H⋯Cl hydrogen bond and an Au⋯Cl contact to form a layer structure parallel to the ac plane. The structures of bis-(piperidinium) tetra-chlorido-aurate(III) chloride, (pipH)2[AuCl4]Cl, 4, and bis-(pyrrolidinium) tetra-bromido-aurate(III) bromide, (pyrH)2[AuBr4]Br, 6, are closely related but not isotypic. Compound 6 crystallizes in space group Ibam; the Au and two Br atoms of the anion lie in the mirror plane x, y, 0, whereas the bromide ions occupy special positions 0, 0.5, 0 and 0, 0.5, 0.25, with site symmetry 2/m. The NH2 group forms a hydrogen bond to one bromide ion, and also a three-centre hydrogen bond to the other bromide atom and to a metal-bonded Br atom. The packing involves chains of hydrogen-bonded pyrrolidinium and bromide ions parallel to the c axis, combined with a layer structure of [AuBr4]- and bromide anions, parallel to the ab plane and involving Au⋯Br and Br⋯Br contacts. Compound 4, however, crystallizes pseudosymmetrically in space group Iba2; two chlorine atoms of the anion lie on the twofold axis 0.5, 0.5, z, and there are two independent cations. The packing is closely similar to that of 6, but there are no N-H⋯Cl hydrogen bonds to metal-bonded chlorines. The contact distances Au⋯Cl are appreciably longer than their Au⋯Br counterparts in 6, whereas the Cl⋯Cl contact is much shorter than Br⋯Br in 6. Tri-bromido-(piperidine-κN)gold(III) crystallizes as its di-chloro-methane solvate, [AuBr3(pip)]·CH2Cl2, 7. It too displays a square-planar coordination at the gold atom. The packing involves hydrogen bonds N-H⋯Br, stacking of neighbouring AuBr3 units by Au⋯Br contacts, and a short Br⋯Br contact; these combine to form a layer structure parallel to the ac plane.

Aziridine had different regioselective ring openings depending on the functional group of its alkyl substituent. In the case of the alkyl group bearing γ-ketone at the C2 substituent of aziridine, the ring opening by the hydroxy nucleophile from H2O occurred by attacking the aziridine carbon at the C2 position. This reaction proceeded efficiently in the presence of CF3CO2H. Interestingly, the same starting aziridine ring bearing the alkyl substituent at the C2 position with the γ-silylated hydroxy group instead of γ-ketone led to the ring-opening reaction by the same oxygen nucleophile at the unsubstituted C3 position, with the breakage of the bond between aziridine N1 nitrogen and carbon at C3. These reaction products were cyclized to afford substituted pyrrolidine and piperidine rings with representative examples of congeners of pseudoconhydrine and monomorine.

The title compound, C6H13N2 +·Cl-, is as an amidinium salt that was isolated as unexpected product from the reaction between aceto-nitrile, chloro-form and pyrrolidine under refluxing conditions. The packing features two N-H⋯Cl hydrogen bonds to generate centrosymmetric tetra-mers (two cations and two anions) and van der Waals inter-actions.

According to the fusion technique create effective multi-target-directed ligands, in this study, we designed and synthesized a series of benzo[d]thiazol-2-yl)-3-(pyrrolidin-1-yl) or 3-(morph- olino-1-yl)propanamide derivatives, and evaluated their inhibitory potency against MAOs, AChE, BuChE by in vitro enzyme effect assays. Based on activity results, we found that derivatives N-(5-methylbenzo[d]thiazol-2-yl)-3-(pyrrolidin-1-yl)propanamide (2 c) and N-(6-bromobenzo[d]thiazol-2-yl)-3-(pyrrolidin-1-yl)propanamide (2 h) showed good inhibitory potency against BuChE with IC50 values of 15.12 μM and 12.33 μM, respectively. Besides, 2 c and 2 h also exhibited selective MAO-B inhibitory effects with inhibition rates of 60.10 % and 66.30 % at 100 μM, respectively. In contrast, all designed derivatives were poor active against AChE and MAO-A at a concentration of 100 μM. The toxicity analysis in vitro by MTT and AO/EB fluorescence staining confirmed that 2 c and 2 h were nontoxic up to 100 μM. Molecular modeling studies showed that 2 c and 2 h could bind to the active site of BuChE. This research paves the way for further study aimed at designing MAO-B and BuChE inhibitors for the treatment of neurodegenerative disorders.

To overcome numerous health disorders, heterocyclic structures of synthetic or natural origin are utilized, and notably, the emergence of various side effects of existing drugs used for treatment or the resistance of disease-causing microorganisms renders drugs ineffective. Therefore, the discovery of potential therapeutic agents that utilize different modes of action is of utmost significance to circumvent these constraints. Pyrrolidines, pyrrolidine-alkaloids, and pyrrolidine-based hybrid molecules are present in many natural products and pharmacologically important agents. Their key roles in pharmacotherapy make them a versatile scaffold for designing and developing novel biologically active compounds and drug candidates. This review aims to provide an overview of recent advancements (especially during 2015-2023) in the exploration of pyrrolidine derivatives, emphasizing their significance as fundamental components of the skeletal structure. In contrast to previous reviews that have predominantly focused on a singular biological activity associated with these molecules, this review consolidates findings from various investigations encompassing a wide range of important activities (antimicrobial, antiviral, anticancer, anti-inflammatory, anticonvulsant, cholinesterase inhibition, and carbonic anhydrase inhibition) exhibited by pyrrolidine derivatives. This study is also anticipated to serve as a valuable resource for drug research and development endeavors, offering significant insights and guidance.