10.1039/c3ob41936c
The research presented in the "Organic & Biomolecular Chemistry" paper focuses on the discovery of potential anti-inflammatory drugs, specifically diaryl-1,2,4-triazoles bearing an N-hydroxyurea moiety, which serve as dual inhibitors of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX). The study involves the synthesis and evaluation of a series of hybrid compounds derived from diaryl-1,2,4-triazole and hydroxamic acid or N-hydroxyurea, designed to act as novel anti-inflammatory agents. The synthesized compounds were biologically tested for their inhibitory activities against COX-2 and 5-LOX in vitro, with compound 15e showing optimal inhibitory activities. The selectivity of these compounds for COX-2 over COX-1 was also evaluated, with 15e demonstrating a selectivity index comparable to celecoxib. Additionally, the anti-inflammatory activity of selected compounds was assessed using xylene-induced ear edema in mice, albumen-induced paw edema in rats, and acetic acid-induced vascular permeability in mice models. The analgesic activity was evaluated using acetic acid-induced writhing response and hot-plate assays. Molecular modeling studies were conducted to understand the binding interactions of compound 15e with COX-2 and 5-LOX. The research suggests that compound 15e may be a promising anti-inflammatory agent for further evaluation. The reactants used in the synthesis include para-position substituted phenylhydrazine hydrochloride, ethyl 3-bromopropionate, hydroxylamine methanol solution, KOH, and various substituted phenyl rings, among others. The analyses involved high-performance liquid chromatography (HPLC), electrospray ionisation (ESI) mass spectrometry, infrared (IR) spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy to determine the structures and purities of the synthesized compounds.
10.1016/j.tetlet.2007.09.037
The research presents a convenient synthetic methodology for preparing a variety of substituted N-hydroxysulfamides, which are structurally similar to N-hydroxyureas, N-hydroxysulfonamides, and sulfamides and exhibit a wide range of biological activity. The key starting material, N-Boc-sulfamoyl chloride, was prepared by reacting t-butanol with chlorosulfonylisocyanate (CSI). This intermediate was then reacted with several O-TBDMS protected hydroxylamines in the presence of triethylamine to form protected N-hydroxysulfamides. These protected sulfamides were further alkylated using Mitsunobu conditions or standard alkylation conditions with alkyl halides to introduce different alkyl groups on the nitrogen atoms. The final deprotection to the desired N-hydroxysulfamides was achieved using trifluoroacetic acid (TFA) and hydrochloric acid (HCl) in methanol. The methodology was extended to synthesize more complex targets such as bis-N-hydroxysulfamides and cyclic N-hydroxysulfamides. Chemicals such as t-butanol, chlorosulfonylisocyanate, O-TBDMS protected hydroxylamines, triethylamine, PPh3, DEAD, alkyl alcohols, alkyl halides, and TFA played crucial roles in the synthesis process.
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