• Journal of Pharmaceutical Investigation
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• v.28 no.4
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• pp.241-247
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• 1998

Ketoconazole is an imidazole antifungal agent which inhibits the biosynthesis of fungal cellmembrane ergosterol and has immunosuppressive properties in vitro. Biphenyl dimethyl dicarboxylate (PMC) has been utilized for antioxidative action and for liver-protective purposes. Studies were undertaken to investigate effects of biphenyl dimethyl dicarboxylate (PMC) on the immunosuppression of ketoconazole in ICR mice. In the combination of PMC and ketoconazole, as compared with the treatment of ketoconazole alone, there were significant increases in activities of natural killer (NK) cells and phagocytes along with circulation leukocytes. The elevation of serum glutamic-pyruvic transaminase (S-GPT) and total protein levels caused by ketoconazole were reduced by the combination of PMC and ketoconazole. In addition, lower serum albumin and albumin/globulin (A/G) ratio were also increased to normal level.

• YAKHAK HOEJI
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• v.51 no.3
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• pp.194-198
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• 2007

The mouse hepatitis virus (MHV-2) induces broad collapses, focal necrosis and cytolysis of hepatocytes, and leads to death after three to five days of intraperitoneal injection in mice. The present study investigated whether the combinatorial treatment of dimethyl dicarboxylate/amantadine (2:1) showed hepatoprotective and/or antiviral properties in MHV-2 infected ICR mice. In the study, we found that dimethyl dicarboxylate/amantadine group (VDDBA) increased the survival rate (30.8%) when compared to positive control, VL (7.7%) and that VDDBA lengthened the survival time (4.2 d)after MHV-2 infection. In addition, ALT and AST were well regulated when treated with VDDBA (p<0.01). Finally, we concluded that those results were probably from the inhibition of viral replication and at least antiproliferative effect on MHV-2.

• Journal of Pharmaceutical Investigation
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• v.26 no.3
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• pp.193-199
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• 1996

The polymorphism of biphenyl dimethyl dicarboxylate was investigated by DSC. From product five crystal forms. Form 1, Form 2, Form 3, Form 4, and Form 5, were characterized and three crystal forms. Form 6, Form 7, and Form 8, were prepared with the recrystallization method. The dissolution patterns of these eight crystal farms were also studied, but there was practically no difference in dissolution rate.

• Archives of Pharmacal Research
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• v.22 no.3
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• pp.255-261
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• 1999

The effect of biphenyl dimethyl dicarboxylate (PMC) on the cellular and nonspecific immunosuppressions by ketoconazole (KCZ) was investigated in ICR mice. PMC at a dose of 6 mg/kg was administered orally to mice daily for 14 consecutive days. KCZ was suspended in RPMI 1640 medium and orally administered at 160 mg/kg/day 2 hrs after the administration of PMC. Immune responses of the delayed-type hypersensitively (DTH) reaction to sheep red blood cells (SRBC), phagocytic activity and natural killer (NK) cell activity were evaluated. DTH reaction to SRBC was enhanced to normal level by the combination of PMC and KCZ, as compared with treatment of KCZ alone. In the combination of PMC and KCZ, as compared with treatment of KCZ alone, there were also significant increases in activities of natural killer (NK) cells and phagocytes along with circulating leukocytes. These findings indicate that PMC shows a significant restoration from the immunotoixc status induced by KCZ.

• Archives of Pharmacal Research
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• v.13 no.3
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• pp.257-260
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• 1990

Hantzch's type reaction of methyl acetopyruvate (2a), methyl 3-aminocrotonate (3) and 3-nitrobenzaldehyde (4) led to dimethyl 3-acetyl-6-methyl-4-(3'-nitrophenyl)-2, 5-dicarboxylate (5a) and methyl 2, 6-dimethyl-5-(1', 2'-dioxo-2'-methoxyethyl)-4-(3' nitrophenyl)- 2, 5-dicarboxylate (5a) and methyl 2, 6-dimethyl-5-(1', 2'-dioxo-2'methoxyethyl_4-(3' nitrophenyl)1, 4-dihydropyridine-3-carboxylate (6a) in 26.7 and 9.2% yield, respectively. On the other hand, methyl 2, 60dimethyl-4-(3'-nitrophenyl)-1, 4-dihydropyridine 3-carboxylate (9) was acylated by ethyl oxaly chloride to give methyl 2, 6-dimethyl-5-(1', 2'-dioxo-2'-ethoxyethyl)-4-(3'-nitrophenyl)-a, 4-dihydropyridine-3-carboxylate (6b) in 76.8% yield.

• Journal of the Korean Applied Science and Technology
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• v.26 no.3
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• pp.317-327
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• 2009

In this study DMT(Dimethylterephthalate), NDC(Dimethyl-2, 6-Naphthalene Dicarboxylate) were used to synthesize polyester polyol which shows enhanced storage stability, improved flame retardancy, and good compressive strength. If DMT and NDC react respectively with DEG(Diethylene Glycol) which is kind of linear diol, the obtained polyester polyols tend to crystallize easily after the reaction. In case of DMT, PA(Phthalic Anhydride) which has asymmetric structure was introduced to retard the crystallization. In case of NDC, DPG(Dipropylene Glycol) which has an methyl side chain was introduced to prevent the crystallization. It was found that to introduce DPG was much more effective method to prevent the crystallization than PA. NDC and DMT were reacted together with DPG for various compositions of NDC:DMT(8:2, 6:4, 4:6 mol ratio). The obtained NDC-DMT-DPG based polyester polyol showed improved flame retardancy, and good compressive strength with increasing the content of NDC.

• Journal of the Korean Chemical Society
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• v.41 no.9
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• pp.483-487
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• 1997

The whole cells of Chromobacterium chocolatum was immobilized in the matrix of polyacrylamide and then used for the hydrolysis of dimethyl-cis-1,3-dibenzyl-2-oxoimidazolidine-4,5-dicarboxylate. This hydrolysis yielded the optically active monoester ( > 96% ee) which is useful as an synthetic intermediate of (+)-biotin. We have studied the optimum condition of hydrolysis by using immobilized cells under variable concentration of substrate, reaction time and pH levels. The activity of lipase in immobilized cell was retained for longer than 4 weeks. The best conversion yield of product was obtained when 2 g of wet cell was immobilized and then reacted with 200 mg of substrate at pH 7.

• YAKHAK HOEJI
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• v.43 no.6
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• pp.827-833
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• 1999

In this study, we have investigated the effect of Biphenyl Dimethyl Dicarboxylate (DDB), a synthetic analogue of Schizandrin C isolated from Schizandrae Fructus on cytochrome $P_450$ lAl and 2Bl, and the protective mechanism against $CCl_4-induced$ hepatotoxicity in rat liver. After DDB was administered into male rats for different periods of time (1~7 days) and with different doses (25, 50, 100 and 200 mg/kg), mRNA levels of CYPlAl were measured by polymearse chain reaction (PCR) and assayed the activities of CYPlAl specific ethoxyresorufin-O-dealkylase (EROD) and CYP2Bl specific benzyloxyresorufin-O-dealkylase (BROD). DDB treatment resulted in increase in CYP2Bl mRNA level and BROD activity, whereas there was no change in CYPlAl mRNA level and EROD activity. This effect of DDB was time-and dose-dependent and reached maximal level by 3 day and 200 mg/kg treatment. In addition, rats were pre-treated with DDB at doses of 25, 50 or 100 mg/kg daily for 4 days, 3-hr after final treatment on the 4th day, $CCl_4$ 0.3ml/kg was intraperitonially injected into the rats to examine the effect of DDB on $CCl_4-induced$ hepatic injury. Serum levels of ALT and AST were determined and histopathological examination was done in rat liver. Furthermore, we have measured hepatic microsomal malondialdehyde(MDA) level, a parameter of lipid peroxidation. Based on serum ALT level and lipid peroxidation, pretreatment of DDB, 50 mg/kg appeared the most protective effect against $CCl_4-induced$ heapatotoxity. These results indicate that DDB stimulates CYP2Bl mRNA level and BROD activity in time and dose dependent manner and suggest that protective effect of DDB on $CCl_4-induced$ hepatotoxicity may be mediated through free radical scavenging.

• Toxicological Research
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• v.11 no.2
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• pp.181-185
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• 1995

To know the mechanism of biphenyl dimethyl dicarboxylate (DDB) in the protection of chemically induced hepatotoxicity, the activity of glutamic pyruvic tran.saminase (GPT) and the level of lipid peroxidation metabolite (malondialdehyde, MDA) and ATP content in hepatocytes were determined in serum and primarily cultured hepatocytes. For in vibo study, rats were pretreated with DDB (300 mg/ kg, p.o.)for 7 days. DDB pretreatment efficiently reduced the elevation of serum GPT activity induced by carbon tetrachloride (1.6 ml/kg, s.c.) and acetaminophen administration (1500 mg/kg, i.p.). In ex vivo study, hepatocytes were isolated from the rats pretreated with DDB (300 mg/kg, p.o.)for 7 days and cultured for 12 hrs before inducing cytotoxicity with chemicals. The MDA formation and the GPT release induced by adriamycin $(1\times10^{-4} mg/ml)$ and cisplatin $(2\times10^{-4} mg/ml)$ were markedly decreased in the hepatocytes from the rats pretreated with DDB as compared to vehicle only. However, DDB pretreatment did not prevent the decrease of ATP contents of hepatocytes induced by cisplatin and adriamycin. In in vitro experiment, DDB was pretreated in primary cultured hepatocytes for 3 days. DDB enhanced the decreases of ATP contents induced by cisplatin and adriamycln. These results suggest that DDB may protect the hepatocytes from injury induced by hepatotoxlcants through inhibiting the lipid peroxidation.

• YAKHAK HOEJI
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• v.44 no.3
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• pp.263-271
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• 2000

In an attempt to develop an injectable form of practically insoluble biphenyl dimethyl dicarboxylate (DDB), the effect of various vehicles, cosolvents and hydrotropic agents was investigated. It was found that polyethylene glycol (PEG) 400 revealed the best solvency toward DDB (17.7 mg/ml at $37^{\circ}C$), and decreasing order of the solubility was as follows: PEG 400>PEG 300>diethylene glycol monoethyl ether (DGME)>PEG-8 glyceryl caprylate/caprate. Among the hydrotropes used, sodium salicylate, sodium benzoate and nicotinamide were effective in increasing the solubility in water. The solubility of DDB in 2 M sodium salicylate, sodium benzoate and nicotinamide solutions was increased 44.3, 23.5 and 44.0 times than that in water, respectively. The addition of sodium salicylate and sodium benzoate to PEG 300-water PEG 400-water and DGME-water cosolvents remarkably increased the solubility of DDB, and significantly retarded precipitate formation when mixed with water Hemolytic properties of DDB injections (2 mg/4~10 ml) in PEG 300-water or DGME-water (60:40 v/v) cosolvents containing sodium benzoate (0.14~0.35 M) were very low. It was concluded from the results that these solutions would be applied to the design of new DDB injections.