Synthesis and CNS depressant activity of some novel 3-[5-substituted 1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3 H)-ones

• Published in: European journal of medicinal chemistry Vol. 43; no. 1; pp. 135 - 141
• Main Authors: Jatav, Varsha, Mishra, Pradeep, Kashaw, Sushil, Stables, J.P.
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 2008; Elsevier
• Subjects: 4(3 H)-Quinazolinones; Animals; Behavior, Animal - drug effects; Biological and medical sciences; Central Nervous System Depressants - chemical synthesis; Central Nervous System Depressants - chemistry; Central Nervous System Depressants - pharmacology; Chemistry, Medicinal; Drug Design; Electroshock; Hypnotics. Sedatives; Life Sciences & Biomedicine; Medical sciences; MES; Mice; Neuropharmacology; Pentylenetetrazole - antagonists & inhibitors; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Quinazolinones - chemical synthesis; Quinazolinones - chemistry; Quinazolinones - pharmacology; Rats; Science & Technology; Subcutaneous pentylenetetrazole induced seizure; Thiadiazoles - chemistry; 4(3 H)-Quinazolinones; MES; Subcutaneous pentylenetetrazole induced seizure; MAXIMAL ELECTROSHOCK; ANTICONVULSANT ACTIVITY; SEMICARBAZONES; subcutaneous pentylenetetrazole induced seizure; AGENTS; 4(3H)-quinazolinones; Nervous system diseases; Psychotropic; Quinazoline derivatives; Epilepsy; Rodentia; Hypnotic; 4(3H)-Quinazolinones; Central depressant; Biological activity; Cerebral disorder; Vertebrata; Mammalia; Mouse; Animal; Styrene derivatives; Central nervous system disease; Subcutaneous administration; Sedative; Chemical synthesis
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2007.02.004

A series of novel 3-[5-substituted phenyl-1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3 H)-ones were synthesized and evaluated for anticonvulsant, sedative-hypnotic and CNS depressant activities. After i.p. injection to mice at doses of 30, 100, and 300 mg/kg body weight 2-styrylquinazolin-4(3 H)-one derivatives were examined in the maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The neurotoxicity was assessed using the rotorod method. Out of eighteen compounds only 4a, 4d, 4e, 4j and 4k showed anticonvulsant activity in one or more test models. All except 4e and 4f exhibited significant sedative-hypnotic activity via actophotometer screen. CNS depressant activity screened with the help of the forced swim pool method resulted into some potent compounds. From the experimental observation it can be concluded that synthesized compounds exhibited relatively better sedative-hypnotic and CNS depressant activities. [Display omitted] A series of eighteen novel 3-[5-substituted phenyl-1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3 H)-ones have been synthesized and evaluated for anticonvulsant, sedative-hypnotic and CNS depression activities. Maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. Experimental observations indicate that synthesized compounds were better sedative-hypnotic and CNS depressant than anticonvulsant.