Synthesis and biological evaluation of some new β-lactam-triazole hybrids

Abstract

A series of novel b-lactams was synthesized from different imines and a special ketene derived from Nendo-5-norbornene-2,3-dicarboxyloylglycine 1 via the [2 ? 2] ketene imine cycloaddition. Then, b-lactams 3a-h were treated with 1-azido-4-nitrobenzene 4 to afford blactam-triazole hybrids 5a-h. Of the twenty-three b-lactams tested against chloroquine-resistant P. falciparum K14 strain, 3a and 3d showed IC 50 \ 20 lM, while 3j, 3m, 5a-5f exhibited IC 50 \ 50. These newly synthesized blactams were also tested against S. aureus, E. coli, P. aeruginosa, C. albicans and C. glabrata and showed no activity below 125 lg/mL.

One‐Pot Multicomponent Synthesis of β‐Lactams via In Situ Generated Imines

“…From our ongoing interest in sequential multi‐component reactions, we now describe an experimentally simple and efficient method to prepare β ‐lactams via a three‐component, single‐pot coupling of aldehydes, primary amines and an acid chloride. This improved method provides easier access to β ‐lactams compared to our previously reported two‐pot protocol,, and requires no catalysts, no solvent and no product separation procedure. We have applied the method to both aryl and heteroaryl aldehydes for the in situ generation of the imines, followed by a Staudinger reaction to provide β ‐lactam adducts in good to excellent yields.…”

“…The β ‐lactam ring is a common structure in chemical, pharmaceutical and materials industries, serving as essential core units in the most widely used antibacterial antibiotics and as valuable synthetic building blocks . From a biological standpoint, β ‐lactams have profound applications as chemotherapeutic agents for treating microbial diseases, cholesterol absorption inhibitors, anti‐HIV compounds, antifungals, anticancer agents, and antimalarial agents . Synthetically, β ‐lactams can be accessed through various methods, including cyclization reactions, carbene insertion reactions, rearrangements of heterocyclic compounds, the Reformatsky reaction, and the ketene‐imine [2+2] cycloaddition .…”

Design, Synthesis and Biological Evaluation of 3-n-Butylphthlide-Edaravone Hybrids as Potential Agents for the Treatment of Cerebral Ischemia

“…Drug hybridization is an attracting design strategy for drug development and research, which combines the pharmacophores of two or more existing drugs to create a single molecule with multiple pharmacological targets to increase their therapeutic potential. There are numerous examples of hybrid molecules applying this approach [16][17][18] , among which is a well known antihypertensive drug in clinical use, prizidilol (3), integrated with hydralazine and a pharmacophoric group responsible for β-blocking activity.…”

Addressing Antimicrobial Resistance through New Medicinal and Synthetic Chemistry Strategies

“…However, this strategy holds the promise of achieving structural novelty, which is a great challenge for medicinal chemistry and an even greater challenge for the design of antimicrobial compounds. 142 Several examples of hybrids [141][142][143][144][145][146][147][148] as antibacterials are discussed briefly below.…”