• Bulletin of the Korean Chemical Society
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• v.30 no.11
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• pp.2707-2712
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• 2009

5-$HT_{3}$ receptor;5-$HT_{3A}$ receptor channel activity;Novel 5-$HT_{3}$ receptor channel current blockers;Chlorophenyl substituted piperazinylethylaminomethylpyrazoles; The 5-$HT_{3A}$ receptors are one of ligand-gated ion channels and are known to be involved in visceral pain, anxiety, or anticancer agent-induced nausea and vomiting. In present study, we designed novel skeletons based on the developed 5-$HT_{3}$ receptor antagonists and evaluated their effects on 5-$HT_{3A}$ receptor channel currents ($I_{5-HT}$) of a series of pyrazole derivatives having N-chlorophenylpiperazine functionality (6-9). We found that most of N-p-chlorophenyl substituted piperazinyl-pyrazole derivatives (7b, 7c, 7e and 7h) exhibited the high potency for the inhibition of $I_{5-HT}$, whereas the compound without chloride (6) or with m-chlorophenyl group (a serious of 8 and 9) showed the low potency. These result indicate that p-chlorophenyl group is might play an important role for increasing the inhibitory potency on $I_{5-HT}$.

• Toxicological Research
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• v.16 no.2
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• pp.141-146
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• 2000

Phthalate esters are used extensively as a plasticizer in the manufacture of plastic products such as PVC bags and medical devices. Recently, phthalate esters have been shown to induce endocrine system mediated responses. However. only a Jew studies have been conducted for estrogenic activity of phthalate esters. In this study estrogenic activities of seven phthalate esters. butyl benzyl phthalate (BBP), di(2-ethylhexyl) phthalate (DEHP), di-n-butylphthalate (DBP), diethylphthalate (DEP), di-n-pentylphthalate (DPP), di-n-propylphthalate (DPrP) and dicyclohexylphthalate (DCHP), were examined in vitro using E-screen assay and competitive binding assay. From the E-screen assay, BBP. DEHP. DBP and DEP showed weak estrogenic activity at the concentration of 5 $\mu\textrm{M}$. The relative proliferative effect (RPE) and the relative proliferative potency (RPP) were 50~70% and 0.01%. respectively, when compared with 500 pM of 17$\beta$-estradiol (E2). In competitive binding assay with the rat uterine estrogen receptor (ER), BBP and DEP showed weak binding potency ［(l/$10^4$~1/$10^5$ of E2］ while DEHP and DBP scarcely bound to ER. These results suggest that some phthalate esters have weak estrogenic activities in vitro.

• Journal of Food Hygiene and Safety
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• v.15 no.2
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• pp.167-172
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• 2000

Lithospermum erythrorhyzon has been used as a red fooddye and traditional Chinese medicine to treat wounds, skin diseases and burns. Platelet activation plays an important role in thrombosis and haemostasis. Here, we studied the inhibition of platelet activation and its active compound from the root of Lithospermum erythrorhyzon. Its ethyl acetate extract inhibited the aggregation of washed rabbit platelets induced by collagen or thrombin. Five naphthoquinone pigments , shikonin , acetylshikonin , is obutylshikonin, $\alpha$-methyl-n-butylshikonin and $\beta$,$\beta$-dimethylacrylshikonin were isolated by means of high pressure liquid chromatography. The structures were determined by comparison of their proton nuclear magnetic resonance spectra. The potency of their inhibition was in the following order : $\beta$,$\beta$-dimethylacrylshikonin$\geq$$\alpha$-methyl-n-butylshikonin>isobutylshikonin>acetylshikonin>shikonin. It is suggested that the size of the aliphatic hydroxy group of shikonin is important for the enhancement of potency.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.117-117
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• 2003

PPARs (peroxisome proliferator activated receptors) are member of nuclear hormone receptors superfamily. Activations of PPARs upon binding with ligands modulate glucose metabolite, differentiation of adipocyte, inflammation response, and so on. Thiazolidinedione analog is one of potential antidiabetic drug that binds and activates PPARν selectively and enhances insulin sensitivity. In an effort to develop novel and effective antidiabetic thiazolidindione analogs, syntheses of benzoxazole and benzothiazole-linked thiazolidinedione analogs were performed via coupling reaction of benzoxazolylalkylaminoethanol with hydroxybenzylthiazolidinedione to develop novel and effective antidiabetic thiazolidindiones. All compounds were evaluated their biological potency by PPARν transactivation assay and revealed the similar potency with Troglitazone. However, lengthening of N-alkyl substituent did not seem to be beneficial for the activity.

• Bulletin of the Korean Chemical Society
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• v.35 no.7
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• pp.2123-2129
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• 2014

Pim kinases are promising targets in the treatment of hematopoietic and solid cancers. Meridianin C was chosen as a starting point to discover novel pim kinase inhibitors. Using known pim kinase's structural information, aminopyrimidine was introduced to provide the hydrogen-bonding interactions with the conserved lysine residue in the ATP binding pocket of all three Pim kinases. Synthesized 3,5-bis(aminopyrimidinyl)indole derivatives showed pan-pim inhibitory activity. Aminoalkyl substituent was attached on the aminopyrimidine to further enhance the potency and physicochemical properties of compound. The research reveals a significative way of designing compounds with high potency and kinase selectivity for pan-pim kinases.

• Bulletin of the Korean Chemical Society
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• v.33 no.11
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• pp.3635-3639
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• 2012

A series of new diarylureas possessing aminoisoquinoline scaffold was synthesized, and their in vitro antiproliferative activity against A375P human melanoma cell line was tested. Compounds 1d, 1l, 1n, 1p, 1q, and 1t showed superior potency against A375P to Sorafenib. The highest potency was shown by compound 1p possessing 3,5-bis(trifluoromethyl)phenyl terminal ring with $IC_{50}$ value of $0.41{\mu}M$.

• Biomolecules & Therapeutics
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• v.11 no.2
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• pp.133-138
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• 2003

The vascular relaxant and antihypertensive effects of newly developed salts of amlodipine-maleate and camsylate-were evaluated on isolated aorta from rats and in spontaneously hypertensive rats, and compared with those of amlodipine besylate, a standard drug. Amlodipine besylate concentration-dependently inhibited $Ca^{2＋}$-induced contraction in depolarised rat aorta($IC_{50}$/: 4.17 nM), with a very slow onset of action. Amlodipine maleate and amlodipine camsylate also showed vascular relaxant effect with a pattern and a potency similar to those of amlodipine besylate($IC_{50}$/: 3.62 and 3.28 nM, respectively). Amloclipine besylate produced a dose-dependent and long-lasting(>10∼24h) antihypertensive effect with a slow onset of action (ED$_{20}$: 2.31 mg/kg) in spontaneously hypertensive rats. Amlodipine maleate and amlodipine camsylate also exerted antihypertensive effects with a pattern and a potency similar to those of amlodipine besylate(ED$_{20}$: 2.09 and 2.21 mg/kg, respectively). These results suggest that amlodipine maleate and amlodipine camsylate are not statistically differ with amlodipine besylate in relaxant effect of $Ca^{2＋}$-induced contraction in depolarised rat aorta and in antihypertensive effect in spontaneously antihypertensive rats.

• Biomolecules & Therapeutics
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• v.12 no.1
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• pp.19-24
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• 2004

The vascular relaxant effect of amlodipine adipate, a new salt of amlodipine, was evaluate in isolated rat aorta, and compared with that of amlodipine besylate. Furthermore, antihypertensive effects were measured in hypertensive rat models, such as spontaneously hypertensive rats (SHR) and rena1 hypertensive rats (RHR). Amlodipine adipate concentration-dependently inhibited $Ca^{2+}$-induced contraction of rat aorta with a very slow onset of action (reached its maximum at 3.5 h;$IC_{50}$: 3.76 nM), having a pattern and a potency similar to those of amlodipine besylate ($IC_{50}$: 4.01 nM). In SHR and RHR, orally administered amlodipine adipate produced a dosedependent and long-lasting (>10-24 h) antihypertensive effect ($ED_{20}$: 2.48 and 1.57 mg/kg, respectively), with a pattern and a potency similar to those of amlodipine besylate ($ED_{20}$: 2.50 and 1.99 mg/kg in SHR and RHR, respectively). These results suggest that amlodipine adipate is a potent and long-lasting antihypertensive agent and that its antihypertensive effect is not significantly different to that of amlodipine besylate.

• Bulletin of the Korean Chemical Society
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• v.35 no.5
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• pp.1365-1374
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• 2014

Thirteen analogs of tridecapeptide ${\alpha}$-factor (WHWLQLKPGQPMY) of Saccharomyces cerevisiae with C- or N-terminal Trp extension and isosteric replacement by Aib at position 8 and 11, Trp at position 13, D-Ala at position 9, and Orn and Glu at position 6 were synthesized and assayed for their biological activity. Receptor binding assay was carried out using our newly developed spectrophotometric method with detector peptide 14. C- or N-terminal extended analogs, ${\alpha}$-factor-$[Trp]_n$ (n =1-5) 1-5 and $[N-Trp]_1$-${\alpha}$-factor 6, were all less active than native ${\alpha}$-factor and gradual decreases in both activity and receptor affinity were observed with greater Trp extension. Trp-substituted analog at position 13, $[Trp^{13}]{\alpha}$-factor 7, exhibited about 2-fold reductions in both activity and receptor affinity. Aib-substituted analogs, $[Aib^8]{\alpha}$-factor 8 and $[Aib^{11}]{\alpha}$-factor 9, showed 5- to 10-fold reduction in activity as well as 3-fold reduction in receptor affinity compared to native ${\alpha}$-factor. $[Orn^6]{\alpha}$-factor 10 demonstrated strong potency with a 7.0-fold increase in halo activity as well as 1.8-fold increase in receptor affinity compared to native ${\alpha}$-factor. For two double substituted analogs, [$Glu^6,{\small{D}}-Ala^9$]${\alpha}$-factor 12 showed the slightly decreased potency in halo activity compared to analog 10, whereas [$Orn^6,{\small{D}}-Ala^9$]${\alpha}$-factor 11 exhibited 15-fold higher halo activity as well as nearly 3-fold higher receptor affinity compared to native ${\alpha}$-factor.

• Archives of Pharmacal Research
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• v.9 no.2
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• pp.99-110
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• 1986

In order to use for metabolic studies of tranylcypromine (TCP), TCP-phenyl-$d_{5}$ was synthesized via the intermediates, 3-benzoylpropionic acid-$d_{5}$ and trans-2-phenylcyclopropanecarboxylic acid-$d_{5}$ -TCP(0.22 mmole/kg) and its deuterated analog were administered s. c. to the rats and GC/MS analyses of the urines led to the detection of N-acetyltranylcypromine (ATCP) and glucuronide conjugate of phenyl-hydroxylated ATCP. MAO activities in rat brain were measured using serotonin as the substrate. In vitro $IC_{50}$ of ATCP was determined to be $10^{-3}M$. The inhibitions by ATCP were not dependent on the preincubation time and were reversed by washing sedimented mitochondrial pellets after the preincubation. In vivo MAO inhibitions at various times of 0.5, 1.5, 3, 6, 12, and 23 hr after the administration of 0.4 mmole/kg (i. p. ) of ATCP were found to be 0.13, 73, 90, 89, and 74 %, respectively. Similarly, the inhibition percents by 0.015 mmole/kg (i. p. ) of TCP were 94, 99, 95, 91, 71 and 49%. The results strongly suggest that deacetylated product of ATCP may account for its in vivo MAO inhibition. The relationship between the metabolism via phenyl-hydroxylation and the in vivo potency of TCP was examined by QSAR study and it was found that groupings discriminating between the compounds with p-substituents and those without them only ensure high correlations, suggesting that ring-hydroxylation which occurs at the para position in most of the compounds is a determining factor to the potency of TCP.