Synthesis and evaluation of 2,6-piperidinedione derivatives as potentially novel compounds with analgesic and other CNS activities.
New 2,6-piperidinediones 2(a-g) and 4(a-d) were prepared by initial condensation of aromatic aldehydes or cycloalkanones with cyanoacetamide to give alpha-cyanocinnamides l(a-g) or cycloalkylidenes 3(a,b) which underwent Michae1 addition with ethyl cyanoacetate or diethylmalonate. Compounds 4(a-d) were alkylated by various alkyl halides to produce the N-alkylated 2,6-piperidinedione derivatives 5(a-m). Some new selected compounds 2(a-c,f), 4(a-d) and 5(e,h,j) were pharmacologically evaluated for potential anticonvulsant, sedative and analgesic activities. These compounds exhibited significant anticonvulsant and analgesic effects after a single I.P. administration 100 mg/kg b.wt. On the other hand all the investigated compounds induced hypnotic activity and prolonged the phenobarbital sodium- induced sleep as compared with the control group and the most potent compound was found to be 2(f).
El Batran
S A
SA
Pharmacology Department, National Research Center, Dokki, Cairo, Egypt. sehamelbatran@yahoo.com
Osman
A E N
AE
Ismail
M M
MM
El Sayed
A M
AM
D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010881:Piperidones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013997:Time Factors
D018712:Analgesics, Non-Narcotic; D000927:Anticonvulsants; D006993:Hypnotics and Sedatives; D010881:Piperidones