In order to find highly active antidiabetic lead compound, sixteen 4-aminobenzoic acid derivatives were designed and synthesized directly through Mannich reaction in the solution of ethanol at 15-35 degrees C with facile method, mild reaction condition and high yield (45%-90%). Fifteen of them are new compounds. Their structures were confirmed by 1H NMR, 13C NMR, IR, ESI-MS and HR-MS. Alpha-glucosidase inhibitory activity of these compounds indicated that most of these compounds possess the activity with the order: 2c > 2b > 2h > 1a > 1f. The structure-activity relationship of these 4-aminobenzoic acid derivatives was also discussed.
4-Aminobenzoic Acid ; chemical synthesis ; pharmacology ; Drug Design ; Glycoside Hydrolase Inhibitors ; Hypoglycemic Agents ; chemical synthesis ; pharmacology ; Mannich Bases ; chemistry ; Molecular Structure ; Structure-Activity Relationship ; alpha-Glucosidases ; metabolism ; para-Aminobenzoates

To optimize the synthetic method and antibacterial activity of fused heterocyclic thiadiazole compounds, cyclocondensation of 2-(4-methoxyphenyl)-5-amino-1,3,4-thiadiazole (2) with alpha-chloro-4-chloro acetophenone (3) resulted in a key intermediate (4), 6 -(4-chlorophenyl)-2-(4-methoxyphenyl)-imidazo-[2,1-b][1,3,4]thiadiazole, which was carried out an nucleophilic substitution with substituted piperazine to give the corresponding free bases of piperazine (5a-5c), then followed by Mannich reaction with heterocyclicamines and formaldehyde to yield the corresponding Mannich bases, (1a-11) as respective hydrochloride salts. The structures were confirmed by IR, 1H NMR, MS and elemental analysis and the antibacterial activities in vitro of fifteen newly synthesized compounds were also tested against Gram positive bacteria and Gram negative bacteria with the standard 2-fold agar dilution method. The antibacterial results showed that the introduction of a polar group resulted in the enhancement of antibacterial activity in vitro. Thus, the structures of these fused compounds could further be investigated.
Anti-Bacterial Agents ; chemical synthesis ; chemistry ; pharmacology ; Bacillus subtilis ; drug effects ; Escherichia coli ; drug effects ; Imidazoles ; chemical synthesis ; chemistry ; pharmacology ; Mannich Bases ; chemistry ; Microbial Sensitivity Tests ; Molecular Structure ; Pseudomonas aeruginosa ; drug effects ; Staphylococcus aureus ; drug effects ; Thiadiazoles ; chemical synthesis ; chemistry ; pharmacology