Design, synthesis, and urease inhibition studies of some 1,3,4-oxadiazoles and 1,2,4-triazoles derived from mandelic acid.
Some new structural type inhibitors of urease, i.e. 2,5-disubstituted-1,3,4-oxadiazoles (4a-e) and 4,5-disubstituted-1,2,4-triazole-3-thiones (5a-e) were synthesized in two steps from mandelic acid hydrazides (2a-e) and aryl isothiocyanates. The hydrazides in turn were synthesized from mandelic acid via esterification. Compounds 4a-e and 5a-e were evaluated against jack bean urease. Compounds 4d, 5b, and 5d were found to be more potent, with IC(50) values of 16.1 +/- 0.12 microM, 18.9 +/- 0.188 microM, and 16.7 +/- 0.178 microM, respectively, when compared to the standard (thiourea; IC(50) = 21.0 +/- 0.011 microM). These compounds may be subjected to further investigations for the development of antiulcer drugs.
Akhtar
Tashfeen
T
Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan.
Hameed
Shahid
S
Khan
Khalid M
KM
Khan
Ajmal
A
Choudhary
Muhammad Iqbal
MI
D000897:Anti-Ulcer Agents; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008333:Mandelic Acids / Q000737:chemistry; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D014510:Urease / Q000037:antagonists & inhibitors*
D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D008333:Mandelic Acids; D010069:Oxadiazoles; D014230:Triazoles; C045575:1,2,4-triazole; D014510:Urease; C037938:mandelic acid