• Archives of Pharmacal Research
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• v.13 no.3
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• pp.240-245
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• 1990

Asymmetric 2, 6-dimethyl-4-aryl-1, 4-dihydropyridine-3, 5-dicarboxylate with [N-(3, 4-methylenedioxybenzyl)-N-methyl] aminoethyl group as the ester moiety and related 1, 4-dihydropyridine derivatives were prepared and tested for the effects on vascular smooth muscles. 2-6-dimethyl-4-(3'-nitrophenyl)1-4-dihydropyridine-3, 5-dicarboxylic acid 3-[N-(3', 4-methylenedioxybenzyl-N-methyl] aminoethyl ester 5-methyl ester (11) and 2, 6-dimethyl-4-(3'-nitrophenyl)-1, 4-dihydropyridine-3, 5-icarboxylic acid 3-[N-2', 3'-methylenedioxybenzyl)-N-methyl] aminoethyl ester 5-ethyl ester (150 showed potent vasodilating activities $IC_{50}$($10_{-8}M$) was 2, 6 and 2.7 for 11 and 15, compared with 3.5 for nicardipine.

• Journal of Pharmaceutical Investigation
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• v.29 no.3
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• pp.227-234
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• 1999

Solid dispersions were prepared to increase the dissolution rate of biphenyl dimethyl dicarboxylate (DDB) using water-soluble carriers such as povidone, copolyvidone, $2-hydroxypropyl-{\beta}-cyclodextrin (HPCD)$, sodium salicylate or sodium benzoate by solvent evaporation method. Solid dispersions were characterized by infrared spectrometry, differential scanning calorimetry (DSC) and powder X-ray diffractometry, dissolution and permeation studies. DDB tablets (7.5 mg) were prepared by compressing the powder mixtures composed of solid dispersions, lactose, com starch, crospovidone and magnesium stearate using a single-punch press. DDB capsules (7.5 mg) were also prepared by filling the mixtures in empty hard gelatin capsules (size No.1). From the DSC and powder x-ray diffractometric studies, it was found that DDB was amorphous in the HPCD or copolyvidone solid dispersions. Dissolution rates after 10 min of DDB alone and solid dispersions (1 : 10) in sodium benzoate, sodium salicylate and copolyvidone were 11.8, 23.5, 22.8 and 82.5%, respectively. Dissolution rates of DDB after 30 min from 1 : 10 and 1 : 20 copolyvidone solid dispersions were 80.5 and 95.0%, respectively. For the DDB tablets prepared using solid dispersions (1 : 20), the initial dissolution rate was dependent on carrier material, and was ranked in order, $Kollidon\;30\;{\ll}$ copolyvidone < HPCD. For the HPCD solid dispersion tablets, dissolution rate reached 97.4% after 15 min, but thereafter slowly decreased to 80.7% after 2 hr due to the precipitation of DDB. However, in the case of copolyvidone solid dispersion tablets, dissolution increased linearly and reached 93.4% after 2 hr. Reducing the volume of test medium from 900 to 300 ml markedly decreased the dissolution rate of the tablets containing 1 : 20 HPCD solid dispersions and 1 : 10 copolyvidone solid dispersion. For 1 : 20 copolyvidone solid dispersion tablets, there was no significant change in dissolution rate up to 1 hr with different volumes of test medium. Preparation of the copolyvidone solid dispersion (1 : 20) in capsules markedly delayed the dissolution (31.2 % after 2hr) due to the limited diffusion within capsules. The permeation rate $(13.4\;g/cm^2\;after\;8\;hr)$ of DDB through rabbit duodenal mucosa from copolyvidone solid dispersion (1 : 10) was markedly enhanced, when compared with drug alone or physical mixtures. From overall findings, DDB formulations containing copolyvidone solid dispersions (1 : 20) could be used to remarkably improve the dissolution rate in dosage form of powders and tablets.

• Proceedings of the Korean Fiber Society Conference
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• 2003.04a
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• pp.341-342
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• 2003

Poly(trimethylene 2,6-naphthalate)(PTN)은 dimethyl-2,6-naphthalene dicarboxylate(NDC)와 1,3-propanediol(PDO)로 합성된 polyester이다. 비록 PTN은 아직 상업화된 resin은 아니지만 Poly(trimethylene terephthalate)(PTT)와 비슷한 화학적 구조를 가지며 PTT 보다 높은 유리전이 온도(72$^{\circ}C$)를 나타내고 있으므로 다양한 분야에 응용될 수 있다. 특히 최근에 1,3-propanediol based polyester는 가스 차탄 특성이 우수하다는 것이 보고되었으며 PTN의 산소, 이산화탄소 등 가스 차단 특성은 poly(ethylene 2,6-naphthalete)(PEN)보다 우수한 것으로 보고되었다. (중략)

• Bulletin of the Korean Chemical Society
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• v.7 no.3
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• pp.166-169
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• 1986

In order to synthesize conformationally rigid etorphine analogues having potentially interesting pharmacological activities, synthesis of compound 3 by the reaction of compound 4 and compound 5 via intramolecular Diels-Alder reaction has been attempted. However, the reaction did not go well and the compound 3 would not be isolated. Therefore, intermolecular Diels-Alder reaction using dimethyl acetylene dicarboxylate was attempted. As shown in scheme 2, Diels-Alder adduct 9 was converted into the target molecule 14 containing the new [2.2.2] bicyclo octane ring in good yields.

• Journal of Veterinary Clinics
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• v.28 no.2
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• pp.249-253
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• 2011

A 4-year-old intact female American Cocker Spaniel presented with lack of appetite, shivering, and abdominal distension. It was initially diagnosed with chronic hepatitis with cirrhosis, by serum chemistry, radiography, ultrasonography, and histopathologic examination following liver biopsy. Abundant copper granules were detected in most hepatocytes with rhodanine stain, with hepatic copper concentration at 1460 ppm (reference range: <400 ppm). Based on these findings, copper-associated hepatitis with cirrhosis was diagnosed and successfully managed with long-term D-penicillamine, s-adenosylmethionine, biphenyl-dimethyl-dicarboxylate and supportive care. The spaniel died 35 months after diagnosis.

• Polymer(Korea)
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• v.35 no.2
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• pp.146-151
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• 2011

The physical properties of poly (ethylene 2,6-naphthalate) (PEN) copolymers were studied. PEN copolymers were synthesized successfully from the mixtures of ethylene glycol(EG), 1,3-propanediol (PD) and l,4-butanediol (BD) with 2,6-dimethyl naphthalene dicarboxylate. The results indicated that PEN copolymers showed an amorphous state when the content of BD(PD) in applied EG/BD(EG/PD) mixtures was less than 40% during the polycondensation. As a result, the lowering of thermal properties, orientation, and mechanical properties was found, however, the dimensional stability was improved. This is a promising result to apply the synthesized PEN copolymers as flexibles substrates.

• Archives of Pharmacal Research
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• v.29 no.5
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• pp.405-411
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• 2006

Biphenyl dimethyl dicarboxylate (DDB) is a hepatoprotectant, which is used as an adjuvant agent in a treatment for chronic hepatitis. Amantadine is an antiviral agent, which is utilized primarily in the treatment of influenza, but also, occasionally in the treatment of hepatitis C. In a previous study, we reported that DDB, coupled with amantadine, would exert an anti-HBV effect, via the induction of interferon-inducible gene expression in the HepG2 2.2.15 cell line. The primary objective of the present study was to determine whether or not DDB and/or amantadine exhibit anti-HBV properties, and what mechanisms of action might be involved in such properties. In our study, we were able to determine that DDB stimulates Jak/Stat signaling, and induces the expression of interferon alpha $(IFN-\alpha)$ stimulated genes, most notably 6-16 and ISG12. In addition, the antiviral effectors induced by $IFN-\alpha$, PKR, OAS, and MxA, were regulated in the presence of DDB at its optimal concentration $(250{\mu}g/mL)$, to a degree commensurate with the degree of induction associated with the $IFN-\alpha$ treated group. Finally, we determined that the replication of pregenomic RNA and HBeAg was inhibited by DDB treatment, and this inhibition was maximized when coupled with the administration of amantadine $(25{\mu}g/mL)$. In conclusion, the results of this study demonstrated clearly that DDB, as well as the combination of DDB/amantadine, directly inhibited $IFN-\alpha$ signaling-mediated replication of HBV in infected hepatocytes, and thus may represent a novel treatment for chronic hepatitis B, which would be characterized principally by its improved safety over other treatment strategies.

• Archives of Pharmacal Research
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• v.28 no.4
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• pp.451-457
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• 2005

Experimental studies have demonstrated that the triple combination of amantadine (A)/ ursodeoxycholic acid (UDCA, U)/ biphenyl dimethyl dicarboxylate (DDB, D) might have a preferential antiviral effect compared with that observed in interferon-induced antiviral signal pathways, such as those of $STAT1\alpha$ and the 6-16 genes. To confirm the results, this study examined whether th signal transduction for the antiviral activity in HepG2 2.2.15 was induced dependently or independently of interferon. To accomplish this, the correlation between the $STAT1\alpha$ and 6-16 genes, and nitric oxide, for the mediation of the antiviral activity was assessed. The increase in nitric oxide in the UDCA groups suggests that the inhibition of viral gene replication was enhanced by the amantadine combinations (AU and AUD), and might be more effective if incubated for longer periods. It was found that $STAT1\alpha$ was activated by the amantadine combination, although to a lesser extent than that of $interferon-\alpha$, and the primary endpoints examined for the inhibition of gene expression (HBsAg and HBcAg) were remarkably well regulated. This suggests that the amantadine triple, or at least the double, combination had better clinical benefits than those of $IFN-\alpha$ and the nucleoside analogue single treatment. This demonstrates that the amantadine combination might be a substitute for the existing HBV therapy if the results of in vivo and in vitro studies concur.

• Journal of the Korean Chemical Society
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• v.57 no.4
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• pp.455-460
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• 2013

A novel and simple method for the synthesis of 2-amino-4H-pyran-3,4,5-tricarboxylate derivative and the evaluation of their antibacterial activity against Pseudomonas syringae, Xanthomonas citi and Pectobacterium carotovorum are reported. The structure of the isolated compounds has been determined by means of $^1H/^{13}C$ NMR and FT-IR Spectroscopy. The reaction of alkyl isocyanides with acetylenic esters in the presence of dimethyl acetone-1,3-dicarboxylate in the present of $BF_3.SiO_2$ at ambient temperature. Some of the compound showed significant inhibition to growth of bacteria.

• Environmental Analysis Health and Toxicology
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• v.13 no.3_4
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• pp.117-123
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• 1998

Paraquat is a useful nonselective herbicide widely used throughout the world. However, accidental or intentional ingestion of the paraquat cause fetal pulmonary injuring. But there is not suitable antidote of paraquat intoxication and therapeutic agents now be used are not effective. So, in this study we intended to evaluate the inhibitory effects of DDB(dimethyl-4,4'dimethoxy-5,6,5',6'-dimethylene dioxyphenyl-2,2'-dicarboxylate) on paraquat toxicity. DDB (100mg/kg) was administered orally to SD rats lhr after paraquat(50mg/kg) injection. After 24 hours, the biochemical parameters of blood and tissues were examined. In paraquat treated groups sGPT, sGOT, BUN, creatinine, MDA and alkaline phosphatase levels in blood and MDA, glucose-6-phosphatase activity in tissues were elevated by 2 to 5 times of normal values. However in schizandrin treated groups, sGPT, sGOT, MDA and alkaline phosphatase activity in blood and MDA and glucose-6-phosphatase activity were significantly decreased to notmal levels but not in biochemical parameters of nephrotoxicity, BUN and creatinine levels. Therefore, we concluded that schizandrin can be used as an antidote of pulmono, hepatotoxicity of paraquat.