Synthesis, Anticonvulsant Activity, and SAR Study of Novel 4‐Quinazolinone Derivatives

Abstract

Series of N-(4-substitutedphenyl)-4-(1-methyl (or 1,2-dimethyl)-4-oxo-1,2-dihydroquinazolin-3(4H)-yl)-alkanamides (5a-j) and 4-chloro-N'-((1-methyl (or 1,2-dimethyl)-4-oxo-1,2-dihydroquinazolin-3(4H)-yl)-alkaloyl)benzohydrazides (6a-f) were designed based on the previously reported essential structural features for anticonvulsant activity. Several amino acids were incorporated within the synthesized quinazolin-4(3H)-ones to improve their bioavailability and the anticonvulsant activity. Synthesis of the target compounds was accomplished in four steps starting from the reaction between N-methyl isatoic anhydride and the appropriate amino acid. Then, the carboxylic acid group was utilized to synthesize the required final structures. The new quinazolinone derivatives were evaluated for their anticonvulsant activity according to the Anticonvulsant Drug Development (ADD) Program protocol. All the 16 new quinazolinones exhibited good anticonvulsant activity; especially 5f, 5b, and 5c showed superior anticonvulsant activities in comparison to the reference drug, with ED values of 28.90, 47.38, and 56.40 mg/kg, respectively.

Synthesis, in vivo and in silico evaluation of novel 2,3‐dihydroquinazolin‐4(1H)‐one derivatives as potential anticonvulsant agents

“…Failure to observe even a threshold seizure (a single episode of clonic spasms of at least 5 s duration) was defined as protection. (Edayadulla & Ramesh, ; Krall et al, ; Noureldin et al, ; Obniska et al, ; Obniska et al, ).…”

“…Untreated control mice can maintain their equilibrium when placed on a rotating roller that was set to accelerate from 0 to 40 rpm in 120 s for a prolonged period of time. Acute motor impairment is present when the test animal fails to maintain equilibrium on the revolving roller for at least 1 min in each of three successive trials (Edayadulla & Ramesh, ; Krall et al, ; Noureldin et al, ; Obniska et al, ; Obniska et al, ).…”

“…In the MES test, animals were subjected to electrical shock through a current of 60 Hz and intensity of 25 mA delivered via ear-lip electrodes for 0.2 s duration. The test compound was considered to be able to inhibit MES-induced seizure spread upon the absence of hind limb tonic extension (Edayadulla & Ramesh, 2015;Krall et al, 1978;Noureldin et al, 2017;Obniska et al, 2015;Obniska et al, 2016).…”

“…Acute motor impairment is present when the test animal fails to maintain equilibrium on the revolving roller for at least 1 min in each of three successive trials (Edayadulla & Ramesh, 2015;Krall et al, 1978;Noureldin et al, 2017;Obniska et al, 2015;Obniska et al, 2016…”

An Efficient One‐Pot Three‐Component Synthesis of Some New 3‐(Benzo[d]thiazol‐2‐yl)‐2‐alkyl‐4(3H)‐quinazolinones Using Silica Sulfuric Acid as a Heterogeneous Catalyst

“…Quinazolin‐4(3 H )‐ones and benzothiazole derivatives are an important class of heterocyclic compounds. Quinazolin‐4(3 H )‐ones possess broad spectrum of biological and pharmaceutical activities , such as antitubercular agents , anti‐influenza , Alzheimer's disease , anti‐inflammatory , antibacterial , antimicrobial , anticonvulsant , antitumor , and potent non‐nucleoside reverse transcriptase inhibitors of human immunodeficiency virus . Furthermore, these heterocyclic compounds were recently isolated from plant sources, for example, the pyrroloquinazolinoquinoline alkaloids, luotonin A1 and B2 , the indolopyrido quinazolinone, rutaecarpin 3 , and 2‐(2‐methyl‐4‐oxo‐4 H ‐quinazoline‐3‐yl)benzoic acid methyl ester 4 , which are useful for their antitumor activity and hypertensive, diuretic, and uterotonic properties (Fig.…”