Fragment Based Design of New H₄ Receptor−Ligands with Anti-inflammatory Properties in Vivo

Abstract

Using a previously reported flexible alignment model we have designed, synthesized, and evaluated a series of compounds at the human histamine H 4 receptor (H 4R) from which 2-(4-methyl-piperazin-1-yl)-quinoxaline ( 3) was identified as a new lead structure for H 4R ligands. Exploration of the structure-activity relationship (SAR) of this scaffold led to the identification of 6,7-dichloro 3-(4-methylpiperazin-1-yl)quinoxalin-2(1 H)-one (VUF 10214, 57) and 2-benzyl-3-(4-methyl-piperazin-1-yl)quinoxaline (VUF 10148, 20) as potent H 4R ligands with nanomolar affinities. In vivo studies in the rat reveal that compound 57 has significant anti-inflammatory properties in the carrageenan-induced paw-edema model.

Research Progress on Application of Organic Diamines and Their Derivatives

“…Quinoxalines are common nitrogen-containing heterocyclic compounds, which appear in many biologically and pharmaceutically active compounds [17][18][19] . They are synthesized from O-phenylendiamine compounds, ethyl pyruvate and α-bromo ketone.…”

An Efficient and Recyclable Nanoparticle-Supported Cobalt Catalyst for Quinoxaline Synthesis

“…Quinoxaline derivatives are attractive N-containing heterocycles and these scaffolds have attracted much attention, not only in synthetic chemistry [1][2][3] but also in the medicinal field [4][5][6][7][8][9][10][11]. These compounds exhibit diverse biological activities, such as antiviral [4,5], antibacterial [6], anti-inflammatory [7], antitumoral [8,9] and anti-HIV properties [10,11].…”

“…These compounds exhibit diverse biological activities, such as antiviral [4,5], antibacterial [6], anti-inflammatory [7], antitumoral [8,9] and anti-HIV properties [10,11]. Examples of quinoxalinecontaining pharmacological entities are shown in Figure 1.…”

A Chalcone‐Based Highly Selective and Sensitive Chromofluorogenic Probe for Trivalent Metal Cations

“…Quinoxalines, also called benzopyrazines, and their derivatives show a broad spectrum of biological activity including antitumor [15], antiviral [16], antituberculosis [17], anti-inflammatory [18,19], anti-protozoal, anti-HIV [20,21], and have been evaluated as anticancer and anthelmintic agents [22].…”