• Archives of Pharmacal Research
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• v.3 no.1
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• pp.37-49
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• 1980

Chlorpropamide, $C_{10}H_{13}N_{2}O_{3}SCI$, forms orthofombic crystals of space group $P_{2}_{ 1}2_{1}2_{1}$ with a 9.066 $\pm$ 0.004, b = 5.218 $\pm$ 0.003, c = 26, 604 $\pm$, 0.008 $\AA$, and four molecules per cell. Three dimensional photographic data were collected with Mo-K$\alpha$ radiation. The structure was determined using Patterson, Fourier and Difference syntheses methods and refined by the block-diagonal least-squares methods with anisotropic thermal parameters for all nonhydrogen atoms and isotropic thermal parameters for all hydrogen atomes. The final R value was 0.10 for the 1823 observed independent reflections. The dihedral angle between the planes through the benzene ring and the urea goup is 99$^{\circ}$. The conformational angle formed by the projection of the S-C(1) with that of N(1)-C(7) when the projection is taken along the S-N(1) bond is 76$^{\circ}$. The molecule appears to form with neighbouring molecules two hydrogen bonds, N(1)..H...O(3) and N(2)-H...0(2) of lengths 2.774 and 2.954$\AA$ respectively related by screw diads parallel to the a axis. Adjacent molecules parallel to b and c axis are bound together by van der Wasls forces.

• Journal of Pharmaceutical Investigation
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• v.19 no.3
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• pp.155-161
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• 1989

Coprecipitates of chlorpropamide (CPA)-sodium deoxycholate (DC-Na) were prepared at various ratios of CPA to the DC-Na. The X-ray diffraction and DSC measurements indicated that CPA in 1:1 and 1:3 w/w CPA-DC-Na coprecipitates did not exist in amorphous form, but the others were amorphous. The dissolution rate of CPA from the CPA-DC-Na coprecipitates increased in distilled water and KP V 2nd disintegration test fluid (pH 6.8), but decreased extremely in KP V 1st disintegration test fluid (pH 1.2). The dissolution rates of CPA-DC-Na coprecipitates were compared with those of CPA alone and CPA-DC-Na physical mixtures. Especially, it was found that the dissolution rate of CPA markedly increased in the case of 1:5 CPA-DC-Na coprecipitate. The concentration of CPA dissolved from CPA-DC-Na coprecipitate reached a plateau within 5-10 min, and thereafter gradually decreased, indicating that CPA released from the coprecipitate was recrystallized.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.198-198
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• 2001

No report has been addressed to the CYP isoforms catalyzing chlorpropamide, a structural analogue of tolbutamide. To evaluate enzyme(s) mediating formation of 2-hydroxycWorpropamide, a major metabolite and identified by LC/Mass and NMR, incubation studies using human liver microsomes and cDNA expressed CYP were performed on the presence or absence of selective inhibitors of each CYP isoform. (omitted)

• YAKHAK HOEJI
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• v.36 no.6
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• pp.518-528
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• 1992

To determine the optimal conformation of sulfonylureas, the correlation between conformation and hypoglycemic activity of the two sulfonylureas of tolbutamide and chlorpropamide as hypoglycemic agent was studied using an empirical potential function (ECEPP/2) and the hydration shell model in the unhydrated and hydrated states. The conformational energy was minimized from several starting conformations with possible torsion angles in each molecule. The conformational entropy change of each conformation was computed using a harmonic approximation. To understand the hydration effect on the conformation of the molecules in aqueous solution, the contribution of water-accessible volume of each group or atom in the lowest-free-energy conformation was calculated and compared each other. From comparison of the computed lowest-free-energy conformations of two sulfonylureas, it could be suggested that the hydration of sulfonylurea moiety is related to increase the hypoglycemic activity. From the calculation results, it was known that the conformational entropy is the major contribution to stabilize the low-free-energy conformations of two sulfonylureas in unhydrated state. Whereas, in hydrated state, the hydration free energy largely contributes to the total free energies of low-free-energy conformations of tolbutamide and conformational entropy contributes to stabilize the low-free-energy conformations of chlorpropamide. The torsion angles from phenyl ring to urea moiety of the low-free-energy conformations of the two sulfonylureas were shown the nearly regular trend. On the basis of these results, the conformation exhibiting the optimal hypoglycemic activity of sulfonylureas and the binding direction to pancreatic receptor site A could be predicted. Also, according to the side chain lengthening of urea moiety, tolbutamide showed various conformational change. Therefore, steric effect may be important factor in the interaction between sulfonylureas and the putative pancreatic receptor.

• Journal of Pharmaceutical Investigation
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• v.12 no.1
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• pp.12-22
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• 1982

The experimental study have showed that the Polygonatum officinale All. contains diosgenin and ${\beta}-sitosterol$ as active components. Even though many experimental studies were reported, still there are many unknown actions of components from the plant. The purpose of this study was to elucidate the mechanism of hypoglycemic action of ether extract of Polygonatum officinale. The hypoglycemic effect of the ether extract was tested in hyperglycemic rats induced experimentally, The effect on plasma free fatty acid and the acute toxicity were also examined by using mouse. The hypoglycemic effect of the ether extract was compared with other oral hypoglycemic agents such as chlorpropamide and buformin. The ether extract of Polyonatum officinale showed a marked hypoglycemic effect by 1 hour after oral administration in hyperglycemic rats and rabbits but the ethanol extract did not exhibit the hypoglycemic effect. The hypoglycemic effect of the ether extract was potentiated by chlorpropamide while buformin was weak.

• 대한임상약리학회:학술대회논문집
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• 1998.12a
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• pp.62-62
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• 1998

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2001.10b
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• pp.198-198
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• 2001

• YAKHAK HOEJI
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• v.30 no.2
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• pp.87-95
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• 1986

Inclusion complexation of $\alpha$-cyclodextrin($\alpha$-CD), $\beta$-cyclodextrin($\beta$-CD) and tri-O-methyl-$\beta$-cyclodextrin(tri-O-methyl-$\beta$-CD) with chlorpamide(CPA) in aqueous solution and in the solid state were studied by the solubility method, spectroscopy (UV, IR), differential scanning calorimetry (DSC) and powder X-ray diffractometry, and all their molar ratios were found to be 1:1. The solid complexes of CPA with three kinds of cyclodextrins were prepared by a freezedrying method, and their dissolution behaviors were examined. As a result, the release of CPA from the inclusion complexes was significantly improved. The intrinsic dissolution rate of CPA in cyclodextrin inclusion complexes was about 51 times ($\alpha$-CD inclusion complex) and 12 tmies ($\beta$-CD inclusion complex) larger than that of intact CPA.