Synthesis and anti-inflammatory activity of 2,3-diaryl-4(3H)-quinazolinones

Abstract

-quinazolinones containing various substituents on diaryl rings have been synthesized and evaluated for their cyclooxygenase-2 inhibitory activity by the colorimetric COX (ovine) inhibitor screening assay and anti-inflammatory activity by the carrageenan-induced rat paw edema assay. 2-(4-Nitrophenyl)-3-(4-tolyl)-4(3H)-quinazolinone showed a maximum COX-2 inhibition of 27.72% at 22 µM concentration in the present series and exhibited a mild anti-inflammatory activity at a dose of 50 mg/kg in carrageenan-induced rat paw edema assay.Keywords: 4(3H)-quinazolinones, COX-2 inhibitors.One of the aims of medicinal chemists is to develop drugs that would hit single targets. Selective drug action is intended to minimize undesired side effects. By optimizing binding to a selected target protein, safe and efficacious drug molecules could be developed for the treatment of a disease. The discovery of isoforms of cyclooxygenase enzyme as COX-1 and COX-2 showed that the side effects of NSAIDs were due to their unwanted inhibition of COX-1 along with the desired blockade of COX-2 enzyme. This discovery led to the development of selective COX-2 inhibitors, which are almost free of gastric side effects and possess potent antiinflammatory activity [1]. The COX-2 inhibitors have been successful in treating such inflammatory diseases as acute pain, rheumatoid arthritis, and osteoarthritis; a few of them are also being studied for treating different types of cancers and Alzheimer's disease [2]. Despite a few latest cautionary reports, COXIB treatment has a high degree of benefit over risk, and the strategies for the use of NSAIDs have been described [3].Unlike classic NSAIDs, which have a diverse class of chemical structures, the selective COX-2 inhibitors can be classified into two classes as (i) acidic methane sulfonamides containing diphenyl ethers, e.g., nimesulide 1 [4] and NS-398 2 [5], and (ii) vicinal diaryl heterocycles with sulfamoyl or methylsulfonyl substitution, e.g., etoricoxib [6], celecoxib [7], refocoxib [8], and valdecoxib [9]. A central carbo/heterocyclic ring system bearing two vicinal aryl moieties is a prerequisite for selective COX-2 inhibitors. A wide variety of heterocycles can serve as a template for COX-2 inhibitors, i.e., pyrazole (celecoxib), isoxazole (valdecoxib, paracoxib sodium), furan (rofecoxib), oxazole (JTE-522), thiophene (DuP-697), pyridine 3 (etoricoxib), pyrazine 4 [10], and quinoxaline 5 [10].

Synthesis and antiproliferative activity of some diaryldiazepines and diarylpyrimidines

“…The present work is in conjunction with our ongoing programme [1][2][3] on the syntheses and biological studies of various diaryl substituted heterocyclic systems. There is an overwhelming evidence indicating that various heterocyclic cores attached to a diaryl system possess diverse pharmacological activities viz., COX II inhibition [4], allosteric modulation of GABA A receptor [5] and estrogen receptor [6], adenosine receptor antagonism [7], selective p38a inhibition [8], cannabinoid receptor antagonism [9], antimitotic activity [10] (combretastatin analogs), antiplatelet activity [11] and anti-HIV-1 activity [12] (TMC-125).…”

Synthesis, Antimicrobial Evaluation, and Docking Studies of Novel 4‐Substituted Quinazoline Derivatives as DNA‐Gyrase Inhibitors

“…USA). 1 H-NMR spectra were recorded on Gemini Varian (Varian, USA) 200 MHz, Bruker (Bruker Bioscience, USA) AV 300 MHz, and Unity (Varian) 400 MHz spectrometer in DMSO-d 6 or CDCl 3 using TMS as an internal standard. Electron impact (EI) and chemical ionization mass spectra were recorded on a VG 7070 H instrument (Micromass, UK) at 70 eV.…”

“…Quinazolines and condensed quinazolines are found to possess potent anticancer [1], antihistaminic [2], and CNS activities like analgesic and anti-inflammatory [3][4][5][6], sedativehypnotic and anticonvulsant [7] activities. Quinazolinones with substitution of ''OCH 2 CONH 2 '' (oxymethylcarbamide) group at the 4 th position have been reported to enhance the biological activities [8].…”

Utility of 2-Methyl-quinazolin-4(3H)-one in the Synthesis of Heterocyclic Compounds with Anticancer Activity

“…A systematic perpusal of literature, reveals that quinazoline derivatives encompass a broad spectrum of pharmaceutical activity profile such as antitumor [4]- [10], anti-HIV [11]- [13], antimicrobial [14]- [16], antibacterial, anti-inflammatory [17]- [20], CNS activity [21]- [23] and cardiovascular activity [24] [25]. The quinazoline nucleus is the scaffold of many antitumor drugs mainly acting as inhibitors of tyrosine kinase receptor (TKR) [26].…”