Acrylamide derivatives as antiallergic agents. I. Synthesis and structure-activity relationships of N-((4-substituted 1-piperazinyl)alkyl)-3-(aryl and heteroaryl)acrylamides.

Abstract

A new series of acrylamide derivatives (7-10) were synthesized. Antiallergic activity of these compounds was evaluated and their structure-activity relationships were examined. Compound 10d, N-[4-(4-diphenylmethyl-1-piperazinyl)butyl]-3-(3-pyridyl)acrylamid e, showed antiallergic activity equivalent or superior to that of ketotifen in the rat passive cutaneous anaphylaxis (PCA) test by oral administration. Compound 10d, unlike ketotifen, had more potent in vitro 5-lipoxygenase inhibitory activity than caffeic acid, whereas its in vitro antihistamine activity was weaker than that of ketotifen. In addition, its inhibitory activity against histamine release from rat mast cells was approximately two-thirds as potent as that of disodium cromoglycate (DSCG). Compound 10d is a promising agent for treating a variety of allergic diseases.

Synthesis of Some <i>N</i>-[(4-Substituted-1-Piperazinyl)-Oxo(Alkyl and Ethylcarbamoyl)]-3-(2-Thiophenyl)Acrylamides as Non-Steroidal Anti-Allergic and Anti-Inflammatory Agents

“…Traditionally symptomatic treatment of allergies and bronchial asthma has been provided by β-sympathomimetic agents, methylxanthines, corticosteroids, and anticholinergics [1][2][3]. Japanese authors have synthesized a series of acrylamide derivatives linked with different piperazines via alkyl chains and proved them as promising anti-allergic candidates (Figure 1(A)) [4][5][6][7].…”

Synthesis of Some Amino Acid and Peptide Conjugates and their Evaluation as Potential Anti-allergic and Anti-inflammatory Agents

“…The promising success of Youshinori Nishikawa et al (1)(2)(3) in designing new antiallergic drugs characterized as an antagonist of histamine as well as inhibitor for the generation of leukotrienes and prostaglandins, has stimulated a research interest. They synthesized orally active anti-allergic compounds having structure [A] with acrylamide segments responsible for inhibition of enzyme 5lipoxygenase which catalyzed the generation of chemical mediators like (leukotrienes) from arachidonic acid and cause allergy.…”