• 약학회지
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• 제44권2호
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• pp.107-114
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• 2000

We have synthesized 4-isonitroso-4H-1-benzopyran and 4-amino-2,3-dihydro -4H-1-benzopyran of chromone derivatives by using condensation method. Physico-chemical properties of these compounds were measured and analyzed by UV and HPLC method. The correlation coefficient of their methanol solutions by UV were 0.9992 and 0.9994, respectively. And oxime compound was resolved within 4 min and had a detection limit of 3 ng at S/N=3 by HPLC using a reversed phase column with three solvents(MeOH, $H_2O$, HAc). The amino compound was resolved within 4.5 min and had a detection limit of 10 ng at S/N=3 by HPLC under the same conditions. Anti-diabetic effect of chromone derivatives were investigated in the streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male Sprague-Dawley rats by injections of STZ (45 mg/kg, i.v). The investigation of the hair growth effect of isonitrosobenzopyran and 4-aminobenzopyran on the hair of black mouse (C57BL/6) was also carried out. The administraion of their ethanol solution to the black mouse (C57BU/6) through skin them promoted the growth of hair.

• Archives of Pharmacal Research
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• 제25권5호
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• pp.664-668
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• 2002

KR-31543,(2S,3R,4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amino]-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-2H-1-benzopyran is a new neuroprotetive agent for ischemia-reperfusion damage. The in vitro and in vivo metabolism of KR-31543 in rats has been studied by LC-electrospray mass spectrometry. Rat liver microsomal incubation of KR-31543 in the presence of NADPH resulted in the formation of a metabolite M1. M1 was identified as N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine on the basis of LC-MS/MS analysis with the synthesized authentic standard. Rat CYP3A1 and 3A2 are the major CYP isozymes involved in the formation of M1.

• Archives of Pharmacal Research
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• 제27권2호
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• pp.239-245
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• 2004

KR-31543, (2S,3R,4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2 -methyl-2H-tetrazol-5-ylmethyl) amino]-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-2H-1-benzopyran, is a new neuroprotective agent for preventing ischemia-reperfusion damage. This study was performed to identify the metabolic pathway of KR-31543 in human liver microsomes and to characterize cytochrome P450 (CYP) enzymes that are involved in the metabolism of KR-31543. Human liver microsomal incubation of KR-31543 in the presence of NADPH resulted in the formation of two metabolites, M1 and M2. M1 was identified as N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine on the basis of LC/MS/MS analysis with a synthesized authentic standard, and M2 was suggested to be hydroxy-KR-31543. Correlation analysis between the known CYP enzyme activities and the rates of the formation of M 1 and M2 in the 12 human liver microsomes have showed significant correlations with testosterone 6$\beta$-hydroxylase activity (a marker of CYP3A4). Ketoconazole, a selective inhibitor of CYP3A4, and anti-CYP3A4 monoclonal antibodies potently inhibited both N-hydrolysis and hydroxylation of KR-31543 in human liver microsomes. These results provide evidence that CYP3A4 is the major isozyme responsible for the metabolism of KR-31543 to M1 and M2.