Synthesis and Anticonvulsant Activities of 3,3-Dialkyl- and 3-Alkyl-3-benzyl-2-piperidinones (δ-Valerolactams) and Hexahydro-2H-azepin-2-ones (ε-Caprolactams)

Abstract

A series of 3-substituted 2-piperidinone (delta-valerolactam) and hexahydro-2H-azepin-2-one (epsilon-caprolactam) derivatives were prepared and evaluated as anticonvulsants in mice. In the 2-piperidinone series, 3,3-diethyl compound 7b is the most effective anticonvulsant against pentylenetetrazole-induced seizures (ED50, 37 mg/kg; PI (TD50/ED50), 4.46), and 3-benzyl compound 4c (ED50, 41 mg/kg; PI, 7.05) is the most effective anticonvulsant against seizures induced by maximal electroshock. By contrast, none of the epsilon-caprolactams tested had anticonvulsant effects below doses causing rotorod toxicity. log P values were correlated with neurotoxicity and [35S]TBPS displacement, but not with anticonvulsant activity. Electrophysiological evaluations of selected compounds from each series indicated that both the delta-valero-lactams and epsilon-caprolactams potentiated GABA-mediated chloride currents in rat hippocampal neurons.

Contribution of Subsaturating GABA Concentrations to IPSCs in Cultured Hippocampal Neurons

“…The ␥-butyrolactones and their derivatives are GABA A modulatory agents of great interest because they demonstrate potent anticonvulsant activity in mice (Klunk et al, 1982a,b;Canney et al, 1991;Holland et al, 1995;Reddy et al, 1996Reddy et al, , 1997. We have recently focused our attention on a new analog, 3,3-diethyl-2-pyrrolidinone (diethyl-lactam) (Fig.…”

1,3-Dipolar cycloaddition of C-aryl-N-phenylnitrones to (R)-1-(1-phenylethyl)-3-[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones: Synthesis and antimycobacterial evaluation of enantiomerically pure spiroisoxazolidines

“…The spiroisoxazolidines were separated by flash column chromatography and their structures are in accord with their 1 H, 13 C and 2D NMR spectroscopic data as described for 4a. The 1 H NMR spectrum of 4a has two doublets at 4.45 and 4.53 ppm (J ¼ 7.…”

“…Piperidones and their derivatives exhibit anticancer [12], anticonvulsant [13], anti-inflammatory [14], and local anaesthetic [15] activities. Recently, we have initiated a research program on the synthesis of a series of novel heterocycles employing tandem/ domino reactions [16] and/or screened them for antimycobacterial activities [17,18].…”

Synthesis and antimicrobial activity of 1-benzhydryl-sulfonyl-4-(3-(piperidin-4-yl) propyl)piperidine derivatives against pathogens of Lycopersicon esculentum: A structure-activity evaluation study

“…The piperidine scaffold as wide-ranging in its therapeutic uses as it is ubiquitously found in drugs. It is a key structural component of successful antiParkinson's drugs (Klockgether et al, 1996) and displays antipsychotic (Fletcher et al, 2002), antiviral (Christopher et al, 2001), metabolic (Lihu et al, 1998), antimicrobial (Ramalingan et al, 2003a(Ramalingan et al, , 2003b(Ramalingan et al, , 2004, antidepressants (Amat et al, 1996), acetylcholinesterase (Jean-Marie et al, 2001), antimalarial (Maniyan et al, 2006), and anticonvulsant activity (Reddy et al, 1997;Matthew et al, 1998). In 1935, Domargk showed the therapeutic value of group of compounds known as sulfonamides.…”