ABSTRACT
A number of new 4(1H)-quinazolinones were synthesized and evaluated in the carrageenin-induced paw edema test. Most of the compounds were obtained by the cyclization of the appropriately substituted anthranilamides with acid chlorides, followed by further chemical transformation. Structure-activity data suggest that 2-isopropyl-1-phenyl-, 2-cyclopropyl-1-phenyl-, and 1-isopropyl-2-phenyl-4(1H)-quinazolinones afford optimal potency and the presence of a halogen atom is preferred for activity. Adrenalectomy does not affect the antiinflammatory test results. The best result taking into account both efficacy and side effects was displayed by 1-isopropyl-(2-fluorophenyl)-4-(1H)-quinazolinone (50).
Subject(s)
Anti-Inflammatory Agents/chemical synthesis , Quinazolines/chemical synthesis , Adrenalectomy , Animals , Anti-Inflammatory Agents/toxicity , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Carrageenan/antagonists & inhibitors , Edema/chemically induced , Edema/drug therapy , Male , Mice , Mice, Inbred Strains , Quinazolines/pharmacology , Quinazolines/toxicity , Rats , Rats, Inbred Strains , Stomach Ulcer/chemically induced , Structure-Activity RelationshipABSTRACT
Some 2-(fluoromethyl) analogues of 2-methyl-3-aryl-4-(3H)-quinazolinones have been synthesized and screened for CNS activities. It was shown that the 2-(fluoromethyl) analogues possess in general more potent CNS depressant activities and less toxicities than their parent compounds. Of particular interest were the 2-(fluoromethyl) analogues (22, 24, and 31) of methaqualone and 6-aminomethaqualone. Compound 24 was more potent in CNS depressant activity and less toxic than methaqualone. Compound 31 exhbited potent central muscle relaxing activity and markedly reduced toxicity as compared with 6-aminomethaqualone.
