• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Current Trends in Toxicological Sciences
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• pp.114-114
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• 2002

Inhibitors of type IV phosphodiesterase (PDE IV) are currently being developed as new therapeutic agents for asthma, chronic obstructive pulmonary disease(COPD) and arthritis. Unfortunately, the anti-inflammatory effect of PDE IV inhibitors has been considered to be associated to some extent with vomiting as adverse effect. The first generation PDE IV inhibitor, rolipram, was known to induce emesis at clinical trials. (omitted)

• 대한수의학회지
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• 제43권4호
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• pp.615-624
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• 2003

Vascular smooth muscle relaxation is modulated by an increase in cGMP subsequent to nitric oxide (NO) production by endothelial cells. The effects of cAMP and cGMP phosphodiesterase (PDE) inhibitors were investigated in phenylephrine-precontracted rat aorta rings by using the specific inhibitors of PDE I, III, IV and V as relaxing agents (calmodulin-activated PDE inhibitors, IBMX and $W_7$, type I; cAMP-specific PDE inhibitors, milrinone, type IV; Ro 20-1724, type III and cGMP-specific PDE inhibitor, zaprinast, type V). All the PDE inhibitors produced a concentration-dependent relaxation in the ring with intact endothelium (+E). Except for milrinone, all the PDE inhibitors-induced relaxations were inhibited by removal of extracellular $Ca^{2+}$, $N^G$-nitro-L-arginine, $N^G$-nitro-L-arginine methyl ester, methylene blue (MS) or nifedipine. The specific PDE I and PDE IV inhibitors both produced endothelium-independent relaxations which were inhibited by MS in -E rings. However, zaprinast had no effect in -E rings. Except for milrinone, sodium nitroprusside (a NO donor)-induced relaxation was significantly augmented by all PDE inhibitors in +E rings. The results suggest that I) the vasorelaxant properties of IBMX, $W_7$, Ro 20-1724 and zaprinast are dependent on endothelium or on interaction with $Ca^{2+}$ regulation, 2) each PDE is differently distributed in vascular tissues (endothelial and smooth muscle cells), 3) the vasodilations of PDE inhibitors are due to the increase of cAMP and cGMP formation through inhibition of cAMP- and cGMP-PDE and 4) the vasodilation action of milrinone does not involve in endothelial-cyclic nucleotide system.

• Biomolecules & Therapeutics
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• 제10권2호
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• pp.117-123
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• 2002

CJ-10882, (E)-[(3-Cyclopentyloxy-4-methoxyphenyl)methylene]hydrazine-carboxamide, is a newly developed type IV phosphodiesterase isozyme (PDE IV) inhibitor. To investigate the subacute toxic effects of CJ-10882, it was administered to both male and female dogs at 0, 25, 50, 100 or 200 mg/kg/day orally for up to 2 weeks. During the test period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross finding, organ weight, and histopathology were evacuated. Several clinical signs were observed in treated dogs at above 25 mg/kg, including salivation and vomiting. A reduction in the body weight was observed in both sexes at above 50 mg/kg. There were no treatment-related effects on mortality, ophthalmoscopy, urinalysis, hematology, sect biochemistry, necropsy findings, and histopathology in any treatment group. The results of this study demonstrate that CJ-10882, a selective Inhibitor of the type IV class of PDE, may cause effects on gastrointestinal tract and salivary glands. Therefore, these organs should be closely examined in studies with other PDE IV inhibitors.

• Archives of Pharmacal Research
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• 제22권2호
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• pp.202-207
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• 1999

New series of catechol ether type derivatives 5, 6 have been synthesized and applied to biological tests. Even though it is ap preliminary data, some of our target molecules show the promising result against PDE IV inhibition. SAR and biological studies with studies with synthetic compounds will be discussed in detail.

• 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.348.1-348.1
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• 2002

We synthesized various catechol ether type derivatives substituted by the hydrazine moiety and evaluated for their ability to inhibit PDE Ⅳ (Phosphodiesterase Ⅳ). These new compounds were synthesized from 4-methoxy-3-hydroxy benzaldehyde through 5 or 7 steps. Some of them have similar or more potent inhibitory activity against PDE Ⅳ than known PDE Ⅳ inhibitor. Ariflo (SB 207499). Structure activity relationship (SAR) and biological studies of described compounds will be discussed in detail. (omitted)

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Current Trends in Toxicological Sciences
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• pp.114-114
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• 2002

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2018년도 춘계학술발표회
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• pp.81-81
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• 2018

The present study was investigated on in vitro anti-obesity effect of 4-hydroxybenzyl alcohol from Cudrania tricuspidata. We isolated various compounds from Cudrania tricuspidata. Among these compounds, anti-obesity effects of 4-hydroxybenzyl alcohol was examined by lipase activity assay, cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase type IV (PDE4) activity assay, and citrate synthase activity assay. 4-hydroxybenzyl alcohol and Cudrania tricuspidata extracts inhibited the enzymatic activities of lipase, PDE4, and citrate synthase. Lipase is known to mediate the hydrolysis of triacylglycerol in adipose tissue and cholesterol esters in other tissue or cells. Also, PDE4 hydrolyses cAMP, a crucial secondary messenger for in metabolic pathways including glucose and lipid metabolism, lipolysis, and thermogenic function. 4-hydroxybenzyl alcohol and Cudrania tricuspidata extracts induced the inhibitory effect against each enzymatic activity on several specific substrates as observed by detection at 405 or 412 nm. These findings might be attributable to the inhibition of adipogenesis, and partial prevention of obesity. In conclusion, these results show that 4-hydroxybenzyl alcohol and Cudrania tricuspidata may be a critical candidate as a natural anti-obesity source.