Green Synthesis and Evaluation of 3-(Aryl)-2-Thioxo-2,3-Dihydroquinazolin- 4(1H)-ones as Novel Anticonvulsant Drugs

Abstract

Epilepsy is a chronic neurological disorder characterized by recurrent seizure attacks which are caused by an abnormal electrical discharge in the brain. Currently, there is a need for improved medicinal agents to treat epilepsy, since the currently available drugs are effective only in 60-80% of epileptic patients. So the indirect type of molecular modeling study was carried out to find out the 3D structural similarity between some reported anticonvulsant drugs and the newly designed quinazolinone derivatives. Thus, a new series of 3-(aryl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-ones were synthesized using an appropriate synthetic route. Microwave radiation provides an alternate to conventional heating for rapid synthesis of drug molecules. The ideal features of microwave-assisted organic synthesis (MAOS) involve reduction of time for a chemical reaction, instantaneous and uniform heating, carrying out solvent free reactions, and possibility of parallel synthesis. It has proved a bonanza for the researchers involved in drug development and discovery processes such as high-speed combinatorial chemistry. In aqueous mediums, it has resulted in the development of relatively sustainable and environmentally benign protocols for the synthesis of novel drugs. MAOS under controlled conditions has many applications in the field of medicinal chemistry and pharmaceutical research. All the newly synthesized compounds were produced in good yield and characterized by I.R, 1H-NMR, and LC-MASS and also evaluated for their anticonvulsant activity by maximal electroshock (MES) model in rats. These findings are helpful to design better quinazolinone derivatives as novel antiepileptic drugs.

An efficient ultrasonic synthetic approach, DFT study, and molecular docking of 6a‐hydroxy‐9‐nitro‐6,6a‐dihydro‐isoindolo[2,1‐a] quinazoline‐5,11‐dione derivatives as algaecides for refining wastewater

“…A series of reactions used in the synthesis of the target algaecide fused quinazolinone-isoindolone hydroxide. The N-heterocyclic compounds have been synthesized in a new sequence of title compounds beginning by reaction of anthranilic acid with 3-nitro phthalic anhydride in the presence of n-butanol to give 2-((2-carboxyphenyl) carbamoyl)-5-nitrobenzoic acid which treated with acetic anhydride to afford 5-nitro-2-(4-oxo-4H-benzo[d] [1,3] oxazin-2-yl)benzoic acid (1a) that is isomerized to 9-nitro-5,11-dioxo-5H-benzo [4,5][1,3]oxazino [2,3-a]isoindol-6a (11H)-yl acetate (1b) was prepared based on the procedures previously reported [19][20][21][22] .…”

“…it allowed to react via nucleophilic center (NH 2 ) beside the electrophilic center (OCOMe) of acetate via bimolecular nucleophilic substitution (SN 2 reaction). The isomers 4a and 4b can be converted to more thermodynamically stable compound 6-amino-isoindolo[2,1-a] [1,3,4]thiadiazolo [2,3-b] quinazoline-9,15-dione (5) and 5-methyl-1,3,4-thiadiazol-2-ylamino-9-nitro-6,6a-dihydroisoindolo [2,1-a]quinazoline 5,11-dione (6), respectively. FTIR spectra for compounds 5 and 6 were characterized by stretching frequency of the hydroxyl, amino, and carbonyl lactam groups at 3512-3487, 3342-3313, and 1671-1665 cm À1 respectively (Scheme 4).…”

“…Quinazolin-4(3H)-ones and their derivatives are versatile heterocyclic nitrogen-containing compounds, usually having very little adverse effect on humans and display a wide variety of biologic activities such as antihistaminic, antimicrobial [1][2][3], algaecides, and antifungal [4][5][6][7]. Consequently, the structures of benzoxazinone and quinazolinone were intensively studied in synthetic chemistry.…”