Synthesis of 2-piperidinecarboxylic acid derivatives as potential anticonvulsants

Discovery of a 3,4,5-trisubstituted-1,2,4-triazole agonist with high affinity and selectivity at the somatostatin subtype-4 (sst4) receptor

“…Amides 11-17 were synthesized from either indoleacetic acid (9) or indole-propionic acid (10) using a mixed anhydride coupling procedure. 36 The 3,4-dichlorophenylacetamide derivative 25 was prepared from tryptamine and thionyl chloride in the presence of triethylamine. All amides could be thionated using Lawesson's reagent in good to excellent yields (18-24 and 26, Scheme 2).…”

Synthesis and anticonvulsant activity of some alkanamide derivatives

“…According top hase1of the anticonvulsants creening project(ASP),twoconvulsantt ests,maximale lectroshock( MES)and pentylenetetrazole (ScPTZ),a reused forprimary evaluation foranticonvulsantactivity and the rotarod test isu sed forprimary toxicity screening [28].The anticonvulsantactivity of the title compounds wasdetermined against MES seizuresduetothe reported datarevealing the anti-MES activity of anilide pharmacophore [9][10][13][14][15][16][17][18][19].The MES test isamodel forgeneralized tonic-clonicseizuresand represents the compoundspreventing seizurespreads [28].The activity dataof the title compoundsagainst MES seizuresinduced 0.5 and 4h afteradministration atasingle dose level of 100 mg/kg aresummarized in Table 4. Also,the primary neurologicaltoxicity of the compoundsdetermined byt he rotarod test ispresented in Table 4.…”

“…Inrecenty ears,one of the common strategiesfort he developmentof the newAEDsismolecularmodification of the knownd rugsormoleculesw ithanticonvulsant activity.Anilide,one of the pharmacophoresw ithanticonvulsantactivity against maximale lectroshockseizures(MES)wass tudied extensivelybyt he research groupsof Clarkand Vamecq [8][9][10][11][12][13][14][15][16].Ho etal. alsostudied anilide derivativesand reported N -(2,6-dimethylphenyl)piperidine-2-carboxamide ast he most active molecule [17].Inthe lightof thesestudies,anti-MES activity of anilide pharmacophorei sdepending on the substitution patternand the natureo fthe substituent on the N -phenylring. Optimalanti-MES activity was arised byintroduction of small and lipophilicsubstituents atpositions2or2and 6of the N -phenylring [10,13,14].…”

New Anticonvulsant Agents

“…The activity of several 2-piperidinecarboxyamides in the MES test in mice has been reported [85,86]. Receptor binding studies indicate that these amides demonstrated weak binding affinity at the phencyclidine (PCP) site on the N-methyl-D-aspartate (NMDA) receptor complex; however, a correlation between affinity and seizure protection in the MES test was not observed.…”