Synthesis of New 2,3‐Dihydroquinazolin‐4(1H)‐one Derivatives for Analgesic and Anti‐inflammatory Evaluation

Abstract

Starting from isatoic anhydrides, several new 2,3-dihydroquinazolin-4(1H)-one derivatives bearing chalcone or pyrazole or thiazole moieties at the third position were synthesized. The analgesic and anti-inflammatory activities for most compounds were studied at a dose level of 50 mg/kg via the acetic-acid-induced writhing-response method and carrageenan-induced edema method, respectively. The study showed that the chalcones bearing a 4-chlorophenyl group 4c or 4-nitrophenyl group 4b were the most active ones as analgesics. Both chalcone 4c and N-phenyl pyrazole bearing 4-methoxy phenyl group 5b showed a higher anti-inflammatory activity than celecoxib but still lower than that of diclofenac sodium. Moreover, the chalcone 4c has nearly the same ulcerogenic index as the selective cyclooxygenase-2 inhibitor celecoxib.

Flavonoids as Anti-Inflammatory and Analgesic Drugs: Mechanisms of Action and Perspectives in the Development of Pharmaceutical Forms

“…El-Sabbagh et al [99] synthesized 2,3-dihydroquinazolin-4 (1H)-one derivatives bearing chalcone moieties. One compound showed a significant analgesic effect in the acetic acid-induced writhing test and in the reduction of carrageenan-induced paw edema compared to celecoxib (a commonly used NSAID that selectively inhibits COX-2), and it also exhibited a similar loss of gastric effects, as compared to celecoxib, which were reduced compared to COX-1 inhibitors, such as indomethacin.…”

Alkylamino‐Directed One‐Pot Reaction of N‐Alkyl Anilines with CO, Amines and Aldehydes Leading to 2,3‐Dihydroquinazolin‐4(1H)‐ones

“…2,3‐Dihydroquinazolin‐4(1 H )‐ones (DHQAs) are an important class of nitrogen‐containing heterocycles with a wide range of pharmaceutical and biological activities such as anticancer, antitumor,, antihypertensive, anti‐inflammatory, antibacterial, antifungal, antipsychotic, antihistaminic, antiviral, anti‐Plasmodium, diuretic,,, vasodilating, analgesic, anthelmintic effects and cathepsins B & H, cholinesterases, coagulation factor Xa, HIV‐1 reverse transcriptase, inosine 5′‐monophosphate dehydrogenase, protein kinase C‐ θ , transient receptor potential melastatin 2 19 inhibition. For example, evodiamine,, and metolazone, are typical representatives of clinically significant DHQA medications (Figure ).…”

Larvicidal Activities of 2-Aryl-2,3-Dihydroquinazolin -4-ones against Malaria Vector Anopheles arabiensis, In Silico ADMET Prediction and Molecular Target Investigation

“…The 2,3-dihydroquinazolin-4(1H)-ones (2,3-DHQs) are fused heterocyclic compounds which exist in natural products such as luotonins A, B, E, and F [13], tryptanthrin [14], and rutaecarpine [15]. 2,3-DHQs possess a broad range of pharmacological properties such as anti-cancer [16,17], antidepressant [18], antidiabetic [19], antifungal [20], antihypertensive [21,22], analgesic, anti-inflammatory [23,24], antibacterial [25], antioxidant [26], and antiviral [27] activities; they also act as bronchodilator [28], centrally acting muscle relaxant [29], diuretic [30], sedative, and hypnotic [31] agents (Figure 1). Quinazoline derivatives were also reported as bactericides [32], fungicides [33], and insecticides [34].…”