Conformational Analysis of Sulfonylureas: Acetohexamide and Tolazamide
정우태(Uoo Tae Chung);강기롱(Kee Long Kang);이성희(Sung Hee Lee)
- Abstract
- Conformational free energy calculations using an empirical potential function and a hydration shell model(program CONBIO) were carried out on hypoglycemic agent acetohexamide and tolazamide in the unhydrated and hydrated states. The initial geometry of sulfonylureas was obtained from X ray crystallographical data and homologous molecular fragments. In both states, the feasible conformations were obtained from the calculations of conformational energy, conformational entropy, and hydration free energy by varying all the torsion angles of the molecules. From the calculation results, it is known that the conformational entropy is the major contribution to stabilize the low-free-energy conformations of two sulfonylureas in both states. But, in hydrated state, the hydration does not directly affect each conformations. The intramolecular hydrogen bonding of sulfonylurea hydrogen and 7-membered nitrogen appeared to the conformations of tolazamide in both states. It is thought that the hydrogen bonding decrease steric hindrance on the receptor binding direction. The substitution of alicyclic or N-heterocyclic ring than that of carbons chain of urea moiety may be properly interaction between sulfonylureas and the putative pancreatic receptor.
- December 2024, 68 (6)
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