Synthesis and anticonvulsant activity of some new 2-substituted 3-aryl-4(3H)-quinazolinones

Abstract

A series of 4(3H)-quinazolinones structurally related to 2-methyl-3-o-tolyl-4(3H)-quinazolinone (methaqualone, 3) were synthesized and evaluated for anticonvulsant activity. Preliminary screening of these compounds revealed that 2-[2-oxo-2-(4-pyridyl)ethyl]-3-aryl-4(3H)-quinazolinones 6l and 8i, 8k, and 8p-r having a single ortho substituent on the 3-aryl group had the most promising anticonvulsant activity. Compounds 6l and 8i possessing 3-o-tolyl and 3-o-chlorophenyl groups, respectively, showed good protection against MES- and scMet-induced seizures, combined with relatively low neurotoxicity after intraperitoneal administration in mice. They also exhibited low toxicity in tests for determining the mean hypnotic dose (HD50) and the median lethal dose (LD50). Although these compounds were markedly more potent as anticonvulsants when administered orally in mice and rats, they were also more neurotoxic. This neurotoxicity was particularly acute in oral tests with rats, which resulted in marginal protective indices. In drug differentiation tests, compound 6l was ineffective against seizures induced by bicuculline, picrotoxin, and strychnine, while 8i showed some protection against picrotoxin-induced seizures.

In silico Design, Synthesis and Pharmacological screening of Quinazolinones as NMDA receptor antagonists for Anticonvulsant activity: Part II

“…SHIMADZU Affinity-I spectrophotometer was for recording the IR spectrum. General synthesis scheme of the target compound [7][8][9][10][11] (SMMB [1][2][3] ) To a solution of barbituric acid (0.01 mol)/ thiobarbituric acid (0.01 mol) in methanol as solvent, formaldehyde (0.02 mol) and 3-amino-2-methylquinazolin-4(3H)-one (0.02 mol) were added drop wise. The reaction mixture was refluxed on a steam bath for 4 hr.…”

Zn[(L)-proline] as a Recyclable and Green Catalyst for Efficient and One-pot Three-Component Synthesis of 1,4-Dihydro- pyridines Under Solvent-Free and Microwave Irradiation Conditions

“…and piriqualone 18 . Quinazolinones are normally prepared by treatment of O-acyl anthranil with primary amines at temperatures above 200 0 C 19 .…”

Silica Supported Zinc (II) Chloride (SiO2-ZnCl2) as an Efficient Catalyst for the Eco-Friendly Synthesis of 2,3-Dihydroquinazolin-4(1H)-Ones

“…In particular dihydroquinazolin-4(1H)-one scaffold were found as a core unit in a number of biologically active compounds that they include anticancer, antidituric, anticonvulsant activities. [1][2][3][4][5][6][7][8] Thus, extensive efforts have been exerted on developing methodology for the synthesis of dihydroquinazolin-4(1H)-one derivative. Several numbers of synthetic strategies are known for the preparation of substituted dihydroquinazolin-4(1H)-ones.…”