• Korean Journal of Clinical Pharmacy
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• v.10 no.3
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• pp.140-144
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• 2000

Reofecoxib는 용량 의존적으로 cyclo-oxygenase-2를 선택적으로 억제한다. 골관절염 환자를 대상으로 하여 이중맹검, 무작위, Western Ontario and McMasters Universi-ties Osteoarthritis Index를 이용하여 평가한 결과, rofecoxib 12.5, 25 mg는 신체적 기능을 크게 향상시키는 것으로 보여졌다. 또한 diclofenac (50 mg, 1일 3회), ibuprofen (800 mg, 1일 3회), nabumetone(1500 mg, 1일 1회)와 유사한 임상효과를 나타내었다. Rofecoxib는 원발성 월경곤란증과 수술 후 치통에 효과적으로 억제하였으며 naproxen sodium과 ibuprofen과 같은 진통 효과를 보였다. Rofecoxib는 안전성 면에서 우수하며 가장 흔한 부작용은 설사, 두통, 오심과 상기도 감염증이다. Rofecoxib 12.5, 25, 50 mg/day를 투여한 골관절염 환자에게서 위장관계 부작용(천공, 궤양, 출혈)은 ibuprofen, diclofenac, nabumetone을 투여한 환자보다 훨씬 낮은 발생빈도를 나타내었다.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.347.4-348
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• 2002

Recently it has been demonstrated that selective cyclooxygenase-2 (COX-2) inhibitors retain the antiinflammatory effect but with markedly reduced GI toxicity compared to non selective inhibitors such as traditional NSAIDs. As a consequence, intense efforts have been made to develop selective COX-2 inhibtors during the last decade. Two compounds in this class. celecoxib and rofecoxib. are already in the market and are proved as potent and selective COX-2 inhibitors with much better gastric tolerance. However. there are still strong domands for a COX-2 inhibitor with improved efficacy and safety profiles. Here we report the synthesis and biological profiles of 1.5- and 4.5-disubstituted imidazole analogues as structural equivalents of cefecoxib and refecoxib. The imidazole analogues are overlapped well whth the 3D srructures of celecoxib and rofecoxib.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.5
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• pp.275-280
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• 2008

A brief ischemic insult induces significant protection against subsequent massive ischemic events. The molecular mechanisms known as preconditioning (PC)-induced ischemic tolerance are not completely understood. We investigated whether kinetic changes of cyclooxygenase (COX)-2 during reperfusion time-periods after PC were related to ischemic tolerance. Rats were given PC by occlusion of middle cerebral artery (MCAO) for 10 min and sacrificed after the indicated time-periods of reperfusion (1, 2, 4, 8, 12, 18 or 24 h). In PC-treated rats, focal ischemia was induced by occlusion of MCA for 24 h and brain infarct volume was then studied to determine whether different reperfusion time influenced the damage. We report that the most significant protection against focal ischemia was obtained in rats with 8 h reperfusion after PC. Administration of indomethacin (10 mg/kg, oral) or rofecoxib (5 mg/kg, oral) 48 h prior to PC counteracted the effect of PC. Immunohistochemical analysis showed that COX-2 and HO-l protein were induced in PC-treated rat brain, which was significantly inhibited by rofecoxib. Taken together, we concluded that the kinetic changes of COX-2 expression during the reperfusion period after PC might be partly responsible for ischemic tolerance.

• Journal of the Korean Orthopaedic Association
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• v.55 no.1
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• pp.9-28
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• 2020

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs worldwide for chronic pain, such as arthritis, and there are many different types depending on their composition and mechanism. After long-term use, various side effects can occur, such as gastrointestinal and cardiovascular complications. With a similar analgesic effect to that of traditional non-selective NSAIDs, cyclooxygenase-2-selective NSAIDs have been highly anticipated, because they could complement gastrointestinal tolerance. On the other hand, because of concerns about cardiovascular safety in 2004 and 2005, and the license withdrawals of rofecoxib and valdecoxib, the interest in the side effects of NSAIDs is increasing. Therefore, it is important to use the necessary drugs at a minimum, considering the side effects and interactions of each drug. This study examined the side effects and characteristics of each NSAID that may occur and reviewed the recent research and guidelines related to the use of non-selective NSAIDs and cyclooxygenase-2-selective NSAIDs.

• Biomolecules & Therapeutics
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• v.9 no.2
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• pp.69-78
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• 2001

Cyclooxygenase (COX) is an enzyme, which catalyzes the production of prostaglandins from arachi-donic acid and exists in two isoforms (COX-1 and COX-2). COX-1 is involved in the maintenance of physiological functions such as platelet aggregation, cytoprotection in the stomach and maintenance of normal kidney function. COX-2 is induced significantly in vivo under inflammatory conditions. COX-1 and COX-2 serve different physiological and pathological functions. All commercially available nonsteroidal antiinflammatory drugs (NSAIDS) are inhibitors of both COX-1 and COX-2. Therefore, selective inhibitors of COX-2 may be effective antiinflammatory agents without the ulcerogenic effects associated with current NSAms. Since the mid 1990s, a number of reports have been appeared on the preparation and biological activity of selective COX-2 inhibitors. Recently celecoxib, and rofecoxib, the representative COX-2 inhibitors, are introduced in the drug market. In this paper the relationship of structure-activity for selective COX-2 inhibitors is reviewed.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.339.1-339.1
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• 2002

Since two selective COX-2 inhibitors. celecoxib and rofecoxib, showed good biological activity as antiinflammatory agents. many medicinal chemists are interested in specific COX-2 inhibitors. The distinguished feature of these drugs is that the 5-membered heterocycle ring is substituted with two aryl groups. Therefore, in this study, we designed a new hydantoin derivatives via the reaction of unnatural amino acids as selective COX-2 inhibitors, In systematically steps. 5-phenyl-1 (or substituted) hydantoin derivatives were prepared through esterification. bromination, C-N bond formation, cyclization from phenyl acetic acid. Particularly. a novel hydantoin ring was converted from unnatural amino acids with potassium isoyanate. In last step. the final analogs were synthesized the substitution at 3-position with alkyl reagents.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.343.1-343.1
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• 2002

Nonsteroidal antiinflammatory drugs(NSAIDs) are widely used to treat pain. fever and inflammatory condition. But chronic-disease patients suffer from gastro-intestinal disturbances such as discomfort. nausea. peptic ulcer and severe bleeding because NSAIDs inhibit not only COX-2 associated with anti-inflammatory activity but also COX-1 associated with adverse gastro-intestinal effects. On the basis of this fact. specific COX-2 inhibitors such as celecoxib and rofecoxib are introduced in the drug market. (omitted)

• Biomolecules & Therapeutics
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• v.20 no.6
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• pp.520-525
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• 2012

Prostaglandin (PG) $E_2$, the most abundant prostaglandin in the human body, is synthesized from arachidonic acid via the actions of cyclooxygenase (COX) enzymes. $PGE_2$ exerts homeostatic, cytoprotective, inflammatory, and in some cases anti-inflammatory effects. Also, it has been reported that $PGE_2$ is involved in hair growth. Diphlorethohydroxycarmalol (DPHC) is a phlorotannin compound isolated from the brown algae Ishige okamurae, with various biological activities in vitro and in vivo. In this study, the biological effect and mechanism of action of DPHC on prostaglandin synthesis in HaCaT human keratinocytes was examined. The results showed that, in these cells, DPHC significantly and dose-dependently induced $PGE_2$ synthesis by increasing the protein and mRNA levels of COX-1 and COX-2. Interestingly, DPHC-induced COX-1 expression preceded that of COX-2. Also, while both rofecoxib and indomethacin inhibited $PGE_2$ production, the latter was seems to be the more potent. From above results, we can expect that DPHC has some beneficial effects via increasing of $PGE_2$ production.

• Journal of Hospice and Palliative Care
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• v.8 no.1
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• pp.57-64
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• 2005

Cyclooxygenase-2 (COX-2) selective inhibitors were specifically developed to reduce the risks of gastrointestinal bleeding associated with other NSAID drugs. However, the APPROVe (Adenomatous Polyp Prevention on VIOXX) trials revealed that rofecoxib sometimes exerts prothrombotic effects. Meanwhile, cancer patients, who also carry a risk of thrombosis due to a variety of mechanisms, are often treated with COX-2 selective inhibitors, due to their relative gastrointestinal safety. This report concerns the case of a 46-year old woman with advanced cervical cancer, who had been treated with opioids and a COX-2 selective inhibitor (celecoxib) for 2 months, for the relief of pain associated with her cancer. The patient was admitted due to swelling of the left leg, which was also accompanied by pain. A computerized tomography scan revealed deep vein thrombosis occurring in multiple veins of both legs. After the administration of low-molecular weight heparin and oral warfarin, the patient's symptoms were relieved initially. However, her prothrombin time was found to be prolonged, necessitating the discontinuation of anticoagulation therapy. The patient's dyspnea worsened, ultimately resulting in her death. In conclusion, the administration of cox-2 selective inhibitors should be carefully considered in patients with a number of different risk factors, and assessed on a case-by-case basis.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.114-121
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• 2023

Selective cyclooxygenase (COX)-2 inhibition is a novel strategy to reduce the risk of gastrointestinal side effects caused by conventional nonsteroidal anti-inflammatory drugs. However, some selective COX-2 inhibitors have become apparent to increase the risk of severe cardiovascular disease. The aim of this study was to examine the anti-inflammatory effect of rosemary extract (RE) and confirm the safety of cardiovascular side effects. Inhibition of COX enzyme activity was assessed, and the levels of COX-2 and prostaglandin E₂ (PGE₂) and COX-1 and thromboxane B₂ (TXB₂) were evaluated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. The 40% RE group showed increased COX-2 inhibition activity in a dose-dependent manner, whereas the 50% RE group only exhibited at 100 ㎍/mL. In a cell-based study, COX-2 mRNA expression was similar in both RE groups and PGE₂ levels tended to decrease in the 40% RE group compared to the LPS group in the LPS pretreatment condition. In the LPS posttreatment condition, the COX-2 mRNA expression decreased in the 40% RE group, and PGE₂ levels were increased in the 40 and 50% RE groups. In both conditions, there was no significant difference in COX-1 and TXB₂ levels. In conclusion, 40 and 50% RE showed significant COX-2 inhibition, similar to the positive control group. It was confirmed that the inhibition of the COX-2 expression, but the effect did not affect the balance between prostacyclin and TXB₂. These results indicate that rosemary showed COX-2 inhibition activity with a low risk of cardiovascular diseases.