Synthesis of certain 1,7,7-trimethyl-bicyclo[2.2.1]heptane derivatives with anticonvulsant, hypoglycemic and anti-inflammatory potential

Starting from (1,7,7-trimethyl-bicyclo2.2.1]hept-2-ylideneamino)-acetic acid methyl esters 6a, 6b, the aryl esters of exo-2-methyl-(1,7,7-trimethyl-bicyclo2.2.1]hept-2-yl)-amino]-ethanol (10a-f) and exo-2-methyl-(1,7,7-trimethyl-bicyclo2.2.1]hept-2-yl)-amino-2-phenyl-ethanol (10g-n) are prepared. Also, from the reaction of 1,7,7-trimethyl-bicyclo2.2.1]heptan nitramine 4 with either 2-amino-1-(4-nitrophenyl)-propane-1,3-diol (17) or 1-aminomethyl-cyclohexanol (18), the alcohol exo-1-(1,7,7-trimethyl-bicylo2.2.1]hept-2-ylamino)-methyl]-cyclohexanol (13), exo-1-(4-aminophenyl)-2-(1,7,7-trimethyl-bicyclo2.2.1]hept-2-ylamino)-propane-1,3-diol (14) and 1-(4-aminophenyl)-2-methyl-1,7,7-trimethylbicyclo2.2.1]hept-2-yl]-amino]-propane-1,3-diol (16) are synthesized. At a dose level of 12.5 mg/kg, compounds 16 and 14 show a significant anticonvulsant protection against pentylenetetrazole seizures (100% and 83% protection, respectively) compared with diphenylhydantoin sodium (50 mg/kg, 100%) and deramciclane fumarate (25 mg/kg, 83%), used as reference drugs. Compound 10b at dose level of 50 mg/kg displayed 41%, hypoglycemic activity, compared with gliclazide (10 mg/kg, 23%) as reference drug. Furthermore, the prepared compounds are screened for their anti-inflammatory potential at a dose level of 50 mg/kg. Compounds 10i, 10g, 14 and 10m exhibited 92%, 90%, 88% and 80% inhibition in rat paw weight, respectively, with no sign of ulcerogenicity, compared with indomethecin (5 mg/kg, 81%).