• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.238.2-238.2
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• 2003

The synthesis of a new series of 1${\beta}$-methylcarbapenems having the substituted aminoethyl-carbamoylpyrrolidine moiety is described. Their in vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of substituent on the pyrrolidine ring was investigated. In particular. the compound 11 g having piperazinyl urea moiety showed the most potent antibacterial activity.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.181.1-181.1
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• 2003

2-Aminoindan derivatives has been shown the serotonergic activities. In order to find new serotonergic agent, we trid to enlarge the indan ring. 3, 4-Dimethoxybenzaldehyde, used as starting material was condensed with malonic acid, piperidine to form 3, 4-dimethoxycinnamic acid. It was catalytically hydrogenated and sudsequently cyclized by Friedel-Crafts acylation reaction to yield 5, 6-dimethoxyindanone. This compound was reacted with pyrrolidine and then acrylamide to be synthesized the 3-membered ring. (omitted)

• The Korean Journal of Physiology and Pharmacology
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• 제7권4호
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• pp.199-205
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• 2003

Osteoblasts are affected by TNF-${\alpha}$ overproduction by immune cells during inflammation. It has been suggested that functional $NF-{\kappa}B$ sites are involved in TNF-${\alpha}$-induced bone resorption. Thus, we explored the effect of pyrrolidine dithiocarbamate (PDTC), which potently blocks the activation of nuclear factor $(NF-{\kappa}B)$, on the induction of TNF-${\alpha}$-induced activation of JNK/SAPK, AP-1, cytochrome c, caspase and apoptosis in MC3T3E1 osteoblasts. Pretreatment of the cells with PDTC blocked TNF-${\alpha}$-induced $NF-{\kappa}B$ activation. TNF-${\alpha}$-induced activation of AP-1, another nuclear transcription factor, was suppressed by PDTC. The activation of c-Jun N-terminal kinase, implicated in the regulation of AP-1, was also down regulated by PDTC. TNF-${\alpha}$-induced apoptosis, release of cytochrome c and subsequent activation of caspase-3 were abolished by PDTC. TNF-${\alpha}$-induced apoptosis was partially blocked by Ac-DEVD-CHO, a caspase-3 inhibitor, suggesting that caspase-3 is involved in TNF-${\alpha}$-mediated signaling through $NF-{\kappa}B$ in MC3T3E1 osteoblasts. Thus, these results demonstrate that PDTC, has an inhibitory effect on TNF-${\alpha}$-mediated activation of JNK/SAPK, AP-1, cytochrome c release and subsequent caspase-3, leading to the inhibition of apoptosis. Our study may contribute to the treatment of TNF-${\alpha}$-associated immune and inflammatory diseases such as rheumatoid arthritis and periodontal diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제13권3호
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• pp.195-200
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• 2009

Zinc released from excited glutamatergic neurons accelerates amyloid ${\beta}$ (A ${\beta}$) aggregation, underscoring the therapeutic potential of zinc chelation for the treatment of Alzheimer's disease (AD). Zinc can also alter A ${\beta}$ concentration by affecting its degradation. In order to elucidate the possible role of zinc influx in secretase-processed A ${\beta}$ production, SH-SY5Y cells stably expressing amyloid precursor protein (APP) were treated with pyrrolidine dithiocarbamate (PDTC), a zinc ionophore, and the resultant changes in APP processing were examined. PDTC decreased A ${\beta}$ 40 and A ${\beta}$ 42 concentrations in culture media bathing APP-expressing SH-SY5Y cells. Measuring the levels of a series of C-terminal APP fragments generated by enzymatic cutting at different APP-cleavage sites showed that both ${\beta}$-and ${\alpha}$-cleavage of APP were inhibited by zinc influx. PDTC also interfered with the maturation of APP. PDTC, however, paradoxically increased the intracellular levels of A ${\beta}$ 40. These results indicate that inhibition of secretase-mediated APP cleavage accounts -at least in part- for zinc inhibition of A ${\beta}$ secretion.

• BMB Reports
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• 제42권3호
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• pp.148-153
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• 2009

Pyrrolidine dithiocarbamate (PDTC) is a stable anti-oxidant or pro-oxidant, depending on the situation, and it is widely used to inhibit the activation of NF-${\kappa}B$. We recently reported that PDTC activates the MIP-2 gene in a NF-${\kappa}B$-independent and c-Jun-dependent manner in macrophage cells. In this work, we found that PDTC activates signal transduction pathways in mouse ES cells. Among the three different mitogen-activated protein kinase (MAPK) pathways, including the extracellular-signal-regulated kinase (ERK), p38 MAP kinase, and stress-activated protein kinase (SAPK)/Jun N-terminal kinase (JNK) pathways, only the ERK pathway was significantly activated in mouse ES cells after stimulation with PDTC. Additionally, we observed a synergistic activation of ERK and induction of c-Fos after stimulation with PDTC in the presence of mouse embryonic fibroblast (MEF) conditioned medium. In contrast, another NF-${\kappa}B$ inhibitor, BMS-345541, did not activate the MAP kinase pathways or induce expression of c-Fos. These results suggest that changes in the presence of the NF-${\kappa}B$ inhibitor PDTC should be carefully considered when it used with mouse ES cells.

• 문화기술의 융합
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• 제7권2호
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• pp.389-394
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• 2021

본 연구에서는 알콕시-아민-알루미늄 유도체인 DPHMP-AlH와 프로피오페논, 부티로페논과의 분자구조 및 경계궤도함수의 특성을 알아보았다. 또한, 전이상태의 입체구조 및 열역학적 파라미터를 계산하여 최종 생성물인 (R),(S)-페닐프로판올과 (R),(S)-페닐부탄올의 선택적 환원에 미치는 영향을 조사하였다. 그 결과 입체 분자구조적 안정성을 고려해 볼 때 (S)형 DPHMP-AlH와 알킬페논의 전이상태가 더 안정한 것으로 나타났으며, 이 결과로부터 DPHMP-AlH와 알킬페논의 선택적 환원으로 얻어진 최종 결과물은 (S)-(1)-페닐프로판올과 (S)-(1)-페닐부탄올의 형성이 유리한 것을 확인하였다.

• Bulletin of the Korean Chemical Society
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• 제29권8호
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• pp.1472-1478
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• 2008

The synthesis of a new series of 1$\beta$-methylcarbapenems having spiro[2,4]heptane moieties is described. Their in vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of substituents at the pyrrolidine ring was investigated. Most of the compounds were found to be more active compared to imipenem against Gram-negative bacteria. A particular compound (IIIc) having 7-oxo-5- azaspiro[2,4]heptane moiety showed the most potent antibacterial activity.

• Biomolecules & Therapeutics
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• 제1권2호
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• pp.143-150
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• 1993

The metabolic profile of triprolidine, 2-[(4-methylphenyl)-3-(1-pyrrolidinyl-1-propenyl)] pyridine, was determined. Urinary extracts obtained with enzyme hydrolysis were derivatized with MSTFA/TMSCl (N-methyl-N-trimethylsilyl trifluoroacetamide/trimethylchlorosilane) and analyzed by GC/MSD. In human urine, which were obtained after the oral administration with triprolidine, hydroxymethyltriprolidine, triprolidine carboxylic acid, oxotriprolidine carboxylic acid and unchanged triprolidine were detected. The maximum urinary excretion rate of triprolidine and hydroxymethyltriprolidine which were extracted from human urine was at 2 to 4 hours after the drug administration. Triprolidine and hydroxymethyl triprolidine were identified by comparison with authentic standards In chromatographic and mass spectral properties. Triprolidine carboxylic acid was detected as a major metabolite of its metabolites in the urine. Oxotriprolidine carboxylic acid and triprolidine carboxylic acid were tentatively identified by the interpretation of its mass spectral patterns. These data suggest that in human, hydroxylation of either the benzyl or pyrrolidine ring can occur during triprolidine elimination.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.342.3-343
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• 2002

Non-insulin dependent diabetes mellitus (NIDDM) is characterized by hyperglycemia, hyperinsulinemia. and impaired insulin action. Insulin resistance is considered to be the underlying mechanism in the pathogenesis of type 2 diabetes. which also leads to dyslipidemia, hypertension. and obesity. Thazolidinediones are a class of oral insulin-sensitizing agents that improve glucose utilization without increasing insulin release. They significantly reduce glucose, lipid and insulin levels in rodent models of NIDDM and obesity, and recent clinical data support theri efficacy in obese diabetic patients. (omitted)

• Macromolecular Research
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• 제8권5호
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• pp.209-214
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• 2000

Polyenaminonitriles containing cycloaliphatic and aliphatic units were prepared by interfacial or solution polymerization reaction of p-bis(1-chloro-2,2-dicyanovinyl) benzene (1) with 4-aminobenzyl-amine, 1-(2-aminoethyl)piperazine, 2-(aminomethyl)pyrrolidine and 4-(aminomethyl)piperidine. The chemical structure of the polymers was confirmed through a syntheses of the model compound. The resulting polymers possessed inherent viscosities of 0.29∼0.62 dL/g and they were easily soluble in polar aprotic solvents and common organic solvents. Thermal properties of the polymers such as curability and stability were studied by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and infrared spectroscopy. The polymers exhibited a large exotherm in DSC analyses and underwent a curing reaction around 340-370$\^{C}$ to form insoluble materials. The polymers showed 70-80% residual weight at 600 $\^{C}$ under nitrogen.