Synthesis, anticonvulsant activity and molecular properties prediction of dialkyl 1-(di(ethoxycarbonyl)methyl)-2,6-dimethyl-4-substituted-1,4-dihydropyridine-3,5-dicarboxylates.

The synthesis and anticonvulsant properties of new N-diethylmalonyl derivatives of nifedipine and other isosteric analogues (7a-7n) were described. Anticonvulsant screening was performed by subcutaneous pentylenetetrazole (scPTZ) and maximal electroshock (MES) induced seizures tests. Majority of the compounds were effective in scPTZ and MES screens. Compound 7k showed good activity displaying maximum protection, which may be due to the presence of styryl moiety at position 4 of 1,4-dihydropyridine nucleus and the methyl groups of diester functionality. Compounds 7a-7d, 7g, 7i and 7k obeyed the Lipinski's "rule of five" and have drug-likeness. Based on computational prediction of molecular and pharmacokinetic properties, it was found that the compounds have good oral absorption.

Design, synthesis and evaluation of dialkyl 4-(benzo[d][1,3]dioxol-6-yl)-1,4-dihydro-2,6-dimethyl-1-substituted pyridine-3,5-dicarboxylates as potential anticonvulsants and their molecular properties prediction.

The present study is on the development of dialkyl 4-(benzo[d][1,3]dioxol-6-yl)-1,4-dihydro-2,6-dimethyl-1-substituted pyridine-3,5-dicarboxylate derivatives as isosteric analogues of isradipine and nifedipine, by the replacement of benzofurazanyl and 2-nitrophenyl groups respectively with benzo[d][1,3]dioxo-6-yl group, as potential anticonvulsants. Fivfteen new derivatives (8a-8o) were synthesized and tested for anticonvulsant activity using maximal electroshock and subcutaneous pentylenetetrazole induced seizure methods. Compound 8f possessing free NH group in 1,4-dihydropyridine ring, diethyl ester functionality at the positions 3 and 5 showed significant anticonvulsant and antioxidant activities. This was also supported by molecular properties prediction data. Selected compounds were evaluated for antinociceptive activity in capsaicin induced nociception assay at 10 mg/kg body weight, but displayed no significant activity at the tested dose.

Comparison of rigid and semirigid fixation for advancement genioplasty.

To compare the skeletal stability of rigid versus semirigid fixation for advancement genioplasty by the assessment of vertical and horizontal measurements pre-operatively and post-operatively on lateral cephalometric radiographs. The study comprised of patients who underwent standard advancement genioplasty by inferior osteotomy of the chin with broadest musculoperiosteal pedicle with either rigid fixation or wire fixation. The displacements of vertical and horizontal measurements resulting following surgery was derived by calculating the difference between preoperative, immediate post-operative and 1 year post-operatively on lateral cephalometric radiographs. Preoperative measurements were marked as T1, immediate post-operative as T2, 1 year follow up post-operative as T3. In the semirigid group a mean horizontal advancement of 5.97 mm was accompanied by a relapse of 1.623 mm during a period of minimum 1 year. The mean superior repositioning of menton was 0.7 mm. This was accompanied by a relapse of 0.325 mm during a period of 1 year. In the rigid group a mean horizontal advancement of 4.815 mm was accompanied by a relapse of 0.2 mm during a period of 1 year. The mean superior repositioning of menton was 0.975 mm. This was accompanied by a relapse of 0.1 mm during a period of 1 year. This study confirms the findings of several previous studies that contribute data specific towards the use of rigid fixation in advancement genioplasty. In our study we also observed that, in cases where large advancements are necessary, wire fixation may offer insufficient means of fixation particularly if the movement is complex and asymmetrical, in which case rigid fixation devices are more helpful.