• Journal of Life Science
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• v.21 no.4
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• pp.481-485
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• 2011

T0901317 is a potent synthetic ligand for liver X receptor (LXR, NR1H2/3), a member of the nuclear receptor superfamily that functions as a transcription factor. However, T0901317 has been also reported to modulate the activity at least four other nuclear receptors (NRs), acting as agonists for farnesoid X receptor (FXR, NR1H4) and pregnane X receptor (PXR, NR1I2) and as antagonists for androgen receptor (AR, NR3C4) and retinoid-related orphan receptor-${\alpha}$ (ROR-${\alpha}$, NR1F1). We report here that T0901317 can also function as an inhibitor for constitutive androstane receptor (CAR, NR1I3). Since CAR is a major player of xenobiotic and cholesterol metabolism in the liver, along with PXR, FXR and LXR, which are reported to be regulated by T0901317, this further complicates the interpretation of potential results with T0901317 in liver cells.

• YAKHAK HOEJI
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• v.35 no.5
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• pp.368-371
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• 1991

For the development of new antiulcer agents 5, 6-dihydroimidazo[2, 1-b]- thiazoles substituted at the 3-position are sythesized. Thus, the reaction of 3-chloromethyl-5, 6-dihydroimidazo[2, 1-b]thiazole(2) with thiourea and subsequently with 3-chloro-propionitrile gives 3-[3-[5, 6-dihydroimidazo[2, 1-b]thiazolyl]methylthio]propionitrile(4), which by partial alcoholysis with methanol is converted into methyl-3-[3-[5, 6-dihydro-imidazo[2, 1-b]thiazoyl]methylthio]propionimidate(5) . This compound(5) is treated finally with sulfamide or sulfonamides. 3-[3-[5, 6-dihydroimidazo[2, 1-b]thiazoyl]methylthiol-N$^{2}$-sulfamoyl-propionamidine(6) inhibited gastric acid secretion (45%) when administered intraduodenally (100 mg/kg) to pylorus-ligated rats.

• Korean Journal of Veterinary Research
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• v.28 no.1
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• pp.17-22
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• 1988

평골근(平滑筋)으로 된 자궁근(子宮筋)은 자동성(自動性)을 가지고 있어서 신경지배(神徑支配)와 관계(關係)없이 근자체(筋自體)로 운동(運動)을 하게 된다. 그러나 이러한 자궁근(子宮筋)의 형태적(形態的) 및 기능적(機能的) 정상상태유지(正常狀態維持)에는 estrogen의 작용(作用)이 불가결(不可缺)한 요소(要素)로 되어 있으며 이 estrogen의 작용(作用)에 의하여 histamine의 자궁근(子宮筋)에 대한 (작용)作用이 수용체(受容體)의 어떤 기전에 의한 것인지를 알기 위하여 본(本) 연구(硏究)는 histamine과 5-hydroxytryptamine 및 이들 길항물질(拮抗物質)들의 자궁근(子宮筋) 운동성(運動性)에 대한 수축(收縮) 및 이완작용(弛緩作用)을 조사(調査)하였다. 자궁근(子宮筋)의 운동성(運動性)은 physiograph를 통(通)해 자궁수축(子宮收縮)의 빈도(頻度)와 크기를 기록하여 아래와 같은 결론(結論)을 얻었다. 1. 5-hydroxytryptamine에 대한 phenoxybenzamine의 억제작용(抑制作用)은 phenoxybenzamine의 길항성(拮抗性)의 결과(結果)이다. 2. histamine은 $H_1$-receptor를 통해서 흰쥐의 자궁평활근(子宮平滑筋)의 운동성(運動性)은 증가(增加)한다. 3. 반면 histamine은 $H_2$-receptor를 통해서는 자궁평활근(子宮平滑筋)의 운동성(運動性)을 이완(弛緩)시켰다. 4. 흰쥐의 자궁근(子官筋)에서 $H_2$-receptor 차단제(遮斷劑)가 $H_1$-receptor 차단제(遮斷劑)의 작용(作用)보다 더욱 강하였다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.60-60
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• 1995

새로운 혈소판 활성화인자 (PAF) 수용체 결합 저해활성 유효성분인 pinusolide ($IC_{50}$/=2.5$\times$$10^{-7}$M)와 arctigenin($IC_{50}$/=5.2$\times$$10^{-6}$M)을 측백엽(Biota orientalis)과 우방자(Arctium lappa)로부터 분리하여 이미 보고한 바 있다. PAF 수용체에 대한 구조활성 상관관계를 규명하고자 또한 용해도가 우수한 강력한 PAF 길항제를 개발하고자 이 길항제들의 유도체들을 다양한 유기화학반응을 이용하여 합성하였고 in vitro PAF receptor binding assay로 그 활성의 강도를 비교 검토하였다. 그 결과, lactone ring 부분은 unsaturated lactone이 saturated lactone보다 활성이 강하였고 ring이 개열되면 활성이 현저히 감소하였다. pinusolide 경우 exocylclic double bond 부분은 sp$^2$구조의 hydrophobic한 유도체가 활성이 강하였으며, methyl ester 부분은 hydrophobic한 유도체가 활성이 강하였다. Arctigenin의 경우 aromatic unit가 hydrophobic할수록 활성이 강하였다.

• The Korean Journal of Food And Nutrition
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• v.10 no.2
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• pp.186-192
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• 1997

Endoscopic diagnosis and medical management from K43 and C45 patients, whose sex, occupation, character and life patterns are quite different each other, were discussed. The K43 was patient with erosive gastritis, which may caused by maldietary habits and life stresses. Although the effective drugs such as H2-receptor antagonists with atacids, H+/K+-pump inhibitors, prokinetics, colloidal bismuth, and sucralfates, were administrated for long time, symptomatic relief of abdominal pain was not improved. The tests of clinical phathology and abdominal sonogram were normal, visceral hypersensitivity was appeared from barostat test of stomach. However C45 had taken headache during every day life, and endoscopically confirmed as a gastric·duodenal ulcer patiant, which may caused by chronic use of NSAIDs. The her ulceric symptoms were suppressed from active stage to healing stage by using combination therapy for H. pylori with traditional antipeptic ulcer drugs, where as amitriptyline was administrated to the K43 but not effective. Nonulcer dyspepsia and irritable bowel syndrome is pooly defined, and affect about 15% of the population annually in U. S. A. but don't seek medical care. Author would like to point out that statistics for visceral pains are absent in Korea.

• Journal of Integrative Natural Science
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• v.8 no.2
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• pp.89-98
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• 2015

Chemoattractant receptor homologous molecule expressed on Th2 cells (CRTh2) is a G-protein coupled receptor targeted for inflammatory diseases such as asthma, allergic rhinitis and atopic dermatitis. In this study, pharmacophore modeling and comparative molecular field analysis (CoMFA) were performed on the series of 2-(2-(benzylthio)-1H-benzo[d]imidazol-1-yl) acetic acids derivatives. Five highly active compounds were used for generation of pharmacophore models using GASP module. The best pharmacophore model was selected and used as template for the alignment of compounds which was used for CoMFA analysis. The best predictions obtained for CoMFA was $q^2=0.545$, $r^2=0.756$. The predictive ability of the model was investigated using 15 test set compounds. Contour maps suggested that presence of bulky substituents at $5^{th}$ position of benzene ring connected to suphur atoms attached to imidazol ring will increase the activity of the compounds. The results obtained from this study will be useful to design more potent CRTh2 antagonists.

• Bulletin of the Korean Chemical Society
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• v.33 no.7
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• pp.2389-2392
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• 2012

• Quality Improvement in Health Care
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• v.9 no.2
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• pp.230-240
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• 2002

Background : The purpose of this study was to develop, implement and evaluate the pharmacist intervention program designed to identify and correctly adjust the dosage of $H_2$-receptor antagonists ($H_2RA$) in renally impaired patients and promote timely conversion of $H_2RA$ from IV to PO therapy. Methods : The study population consisted of renally impaired patients who received $H_2RA$ therapy from April 9 to May 8, 2001 at Hallym Medical Center. Each morning a specifically developed software program identified patients with serum creatinine (Scr) greater than 1.2 mg/dl or age greater than 65 years. The pharmacist, then screened the pharmacy profiles of the identified patients to determine if the patient was on $H_2RA$. For these patients on $H_2RA$ with renal impairement the creatinine clearance (CrCl) was calculated using Cockroft & Gault equation. The pharmacist determined the proper dosage for each identified patients based on the calculated CrCl and the oral dosage that would be appropriate for whom IV therapy was no longer indicated. Result : A total of 149 cases (101 patients) were monitored during the study period. The dosage was inappropriately prescribed for renal function in 61 of 149 cases (41%), and of those, pharmacist made recommendations for 58 cases of which 33 cases (57%) were accepted by the physicians. The administration route of H2RA was inappropriately used as IV in 22 of 53 cases (42%), and pharmacist made recommendations for those 22 cases of which 15 cases (68%) were accepted. Conclusion : Monitoring of patients with renal dysfunction by a pharmacist improved the dosing of $H_2RA$ and a dosing program of patients with renal impairment would be of benefit to other clinicians and institutions seeking to optimize patient care.

• Journal of Integrative Natural Science
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• v.8 no.1
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• pp.1-12
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• 2015

CRTh2 receptor is an important mediator of the inflammatory effects and act as beneficial target for the treatment of asthma, COPD, allergic rhinitis and atopic dermatitis. In the present work, Hologram QSAR studies were conducted on a series of 50 training set CRTh2 antagonists (2-(2-(benzylthio)-1H-benzo[d]imidazol-1-yl acetic acids). The best HQSAR model was obtained using atoms, bonds, connections and donor/acceptor as fragment distinction parameter using hologram length 257 and 6 components with fragment size of minimum 7 and maximum 10. Significant cross-validated correlation coefficient ($q^2=0.786$) and non cross-validated correlation coefficients ($r^2=0.954$) were obtained. The model was then used to evaluate the 15 external test compounds which are not included in the training set and the predicted values were in good agreement with the experimental results ($r^2_{pred}=0.739$). Contribution map show that presence of C ring and its substituents makes big contributions for activities. The HQSAR model and analysis from the contribution map could be useful for further design of novel structurally related CRTh2 antagonists.

• Bulletin of the Korean Chemical Society
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• v.34 no.8
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• pp.2305-2310
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• 2013

A novel series of 2-heteroaryl substituted benzimidazole derivatives, containing the piperidinylphenyl acetamide group at the 1-position, were synthesized and evaluated as MCH-R1 antagonists. Extensive SAR investigation probing the effects of C-2 heteroaryl group led to the identification of 2-[2-(pyridin-3-yl)ethyl] analog 3o, which exhibits highly potent MCH-R1 binding activity with an $IC_{50}$ value of 1 nM. This substance 3o also has low hERG binding activity, good metabolic stability, and favorable pharmacokinetic properties.