Design and synthesis of some new 1-phenyl-3/4-[4-(aryl/heteroaryl/alkyl-piperazine1-yl)-phenyl-ureas as potent anticonvulsant and antidepressant agents

• Published in: Archives of pharmacal research 2016, 39(5), , pp.603-617
• Main Authors: Mishra, Chandra Bhushan, Kumari, Shikha, Tiwari, Manisha
• Format: Article
• Language: English
• Subjects: Animals; Anticonvulsants - chemical synthesis; Anticonvulsants - chemistry; Anticonvulsants - therapeutic use; Anticonvulsants - toxicity; Antidepressive Agents - chemical synthesis; Antidepressive Agents - chemistry; Antidepressive Agents - therapeutic use; Antidepressive Agents - toxicity; Behavior, Animal - drug effects; Biological Availability; Dose-Response Relationship, Drug; Drug Design; Female; Male; Medicine; Mice; Molecular Structure; Motor Activity - drug effects; Pharmacology/Toxicology; Pharmacy; Phenylurea Compounds - chemical synthesis; Phenylurea Compounds - chemistry; Phenylurea Compounds - therapeutic use; Phenylurea Compounds - toxicity; Piperazines - chemical synthesis; Piperazines - chemistry; Piperazines - therapeutic use; Piperazines - toxicity; Rats, Wistar; Research Article; Rotarod Performance Test; Seizures - drug therapy; 약학
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-016-0720-1

A series of 1-phenyl-3/4-[4-(aryl/heteroaryl/alkyl-piperazine1-yl)-phenyl-urea derivatives (29 – 42) were designed, synthesized and evaluated for their anticonvulsant activity by using maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) seizure tests. The acute neurotoxicity was checked by rotarod assay. Most of the test compounds were found effective in both seizure tests. Compound 30 (1-{4-[4-(4-chloro-phenyl)-piperazin-1-yl]-phenyl}-3-phenyl-urea) exhibited marked anticonvulsant activity in MES as well as scPTZ tests. The phase II anticonvulsant quantification study of compound 30 indicates the ED 50 value of 28.5 mg/kg against MES induced seizures. In addition, this compound also showed considerable protection against pilocarpine induced status epilepticus in rats. Seizures induced by 3-mercaptopropionic acid model and thiosemicarbazide were significantly attenuated by compound 30 , which suggested its broad spectrum of anticonvulsant activity. Interestingly, compound 30 displayed better antidepressant activity than standard drug fluoxetine. Moreover, compound 30 appeared as a non-toxic chemical entity in sub-acute toxicity studies.