Synthesis and computational validation of 4- substituted phenyl containing suitably functionalized homo and heterocyclic systems as novel Antiasthmatic agents

Abstract

The term Asthma is used to describe episodic shortness of breath. It is a chronic inflammatory disease of the airways characterized by fibrosis of the airways, hyperplasia and hypertrophy of smooth muscle cells and mucous secreting cells due to infiltration of activated eosinophils and activation of resident mast cells and lymphocytes. Most of the therapies followed currently for asthma, provide only symptomatic relief to patients and do not control inflammation, is being of much concern to us. Therefore, therapies directed towards lowering inflammation, thereby reducing airway reactivity and asthma severity are being emerging trends to cure asthma look quite promising. Now much of the research in asthma has been focused on pro-inflammatory mechanisms and mediators involved in this complex inflammatory process. One of the modern approaches in this area is to target cytokines and develop cytokine modulators as drugs are also being of much interest to us. Development of cytokine modulators as drugs being a novel approach to treat asthma and also the fact that Interlukin-5 (IL-5) is known to induce the mobilization of eosinophils and eosinophil precursors into the circulation. Once recruited from the circulation, these eosinophils are primed for ligand mediated generation of increased amounts of Cysteinyl-Leukotrienes (Cys-LTs) and for cytotoxicity to other cells such as airway epithelium. Recently there has been increasing clinical and experimental evidence that human eosinophils play a key role in the pathogenesis of bronchial asthma and airway hyperresponsiveness. An increased number of eosinophils in circulation and Bronchoalveolar Lavage Fluids (BALFs) have been reported as a characteristic feature of chronic bronchial asthma. The mechanism of eosinophilia in circulation and BALFs is unclear, but recent research findings offer several explanations..