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Synthesis, conformational assignment, and anti-inflammatory activities of N-arylidene-2-(4-chloro-2-(2-substituted phenoxy)phenyl)acetic acid hydrazides

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Abstract

A series of N-arylidene-2-(4-chloro-2-(2-fluoro or chlorophenoxy)phenyl)acetic acid hydrazides (16 or 17) was synthesized for their anti-inflammatory activity by the condensation of corresponding hydrazide and aromatic aldehydes. Characterization of these compounds by proton nuclear magnetic resonance showed most of the protons as two separate peaks. The energy was calculated for each possible configuration, and their stereochemical behavior was studied using proton nuclear magnetic resonance techniques. The results indicated that the most stable stereoisomers are the two E geometrical isomers, which undergo a rapid cis/trans amide equilibrium with the cis conformer predominating. These analogs exhibited moderate to excellent anti-inflammatory activity in carrageenan-induced rat paw edema assay. Among them, N-(3,4-dimethoxybenzylidene)-2-(4-chloro-2-(2-chlorophenoxy)phenyl)acetic acid hydrazide (17k) showed the highest anti-inflammatory activity relative to diclofenac sodium acid as a reference drug (86 % vs. 61 % reduction in inflammation post drug administration, respectively).

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Acknowledgments

This work was supported by grants from the Medicinal Chemistry Center of Excellence and Research Council of Tehran University of Medical Sciences (grant No: 92-03-33-24361).

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Authors and Affiliations

  1. Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, 14176, Iran

    Afraz Nakhostin, Mahsa Toolabi, Mohsen Amini, Abbas Shafiee & Latifeh Navidpour

  2. Pharmacology and Toxicology Department, Pharmaceutical Sciences Branch and Pharmaceutical Sciences Research Center, Islamic Azad University, Tehran, Iran

    Samaneh Mirseyyedhosein, Pariya Khodabakhsh, Helia Aghamiri, Soheila Ghaffari & Hamed Shafaroodi

  3. School of Chemistry, College of Science, University of Tehran, Tehran, Iran

    Alireza Shayesteh

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  1. Afraz Nakhostin
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  2. Samaneh Mirseyyedhosein
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  9. Mohsen Amini
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Correspondence to Latifeh Navidpour.

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Nakhostin, A., Mirseyyedhosein, S., Toolabi, M. et al. Synthesis, conformational assignment, and anti-inflammatory activities of N-arylidene-2-(4-chloro-2-(2-substituted phenoxy)phenyl)acetic acid hydrazides. Med Chem Res 25, 2220–2236 (2016). https://doi.org/10.1007/s00044-016-1656-1

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