• 약학회지
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• 제39권3호
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• pp.329-336
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• 1995

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 crystallographieal 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 conformations] entropy is the major contribution to stabflize 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.

• Archives of Pharmacal Research
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• 제11권1호
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• pp.74-79
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• 1988

Crystals of tolazamide, $C_{14}H_{21}N_3O_3S$, are triclinic space group $P{\bar{1}}$ with cell dimensions of a = 6.355 (2), b = 9.223 (2), c = 13.510 (3) A, ${\alpha}\;=\;101.04\;(8),\;{\beta}=92.80(5),\;{\gamma}\;=\;85.72\;(6)^{\circ}$ and Z = 2. Intensities were collected on an automated four-circle diffractometer using graphite-monochromated Cu K ${\alpha}$ radiations. The structure was solved by direct method and refined by full-matrix least-squares to an R factor of 0.058 for 1184 observed reflections. The molecules are dimerized by the $N-H{\cdots}O$ hydrogen bonds. There are only van der Waals interactions between these molecular dimers.

• The Korean Journal of Physiology and Pharmacology
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• 제19권3호
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• pp.197-202
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• 2015

Sulfonylureas are widely used as an antidiabetic drug. In the present study, the effects of sulfonylurea administered supraspinally on immobilization stress-induced blood glucose level were studied in ICR mice. Mice were once enforced into immobilization stress for 30 min and returned to the cage. The blood glucose level was measured 30, 60, and 120 min after immobilization stress initiation. We found that intracerebroventricular (i.c.v.) injection with $30{\mu}g$ of glyburide, glipizide, glimepiride or tolazamide attenuated the increased blood glucose level induced by immobilization stress. Immobilization stress causes an elevation of the blood corticosterone and insulin levels. Sulfonylureas pretreated i.c.v. caused a further elevation of the blood corticosterone level when mice were forced into the stress. In addition, sulfonylureas pretreated i.c.v. alone caused an elevation of the plasma insulin level. Furthermore, immobilization stress-induced insulin level was reduced by i.c.v. pretreated sulfonylureas. Our results suggest that lowering effect of sulfonylureas administered supraspinally against immobilization stress-induced increase of the blood glucose level appears to be primarily mediated via elevation of the plasma insulin level.