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排序方式: 共有117条查询结果,搜索用时 31 毫秒
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Kikelj D 《Pathophysiology of haemostasis and thrombosis》2003,33(5-6):487-491
The central position of thrombin in the coagulation cascade has made it a popular target for discovery of novel antithrombotic agents. Starting with hirudin, a natural peptide isolated from the medicinal leech, its shorter synthetic analogue hirulog, and argatroban,the first therapeutically used synthetic small-molecule thrombin active site inhibitor, hundreds of direct thrombin inhibitors have been discovered over the last 20 years. Most of them are peptidomimetic compounds,based on the amino acid sequence of fibrinogen which binds into the thrombin active site. Since elucidation of the crystal structure of human thrombin in 1989, the structure-based design of low-molecular-weight peptidomimetic thrombin inhibitors has been greatly aided by the use of x-ray crystallographic analysis of thrombin-inhibitor complexes. The ultimate goal of most research programmes and drug optimization strategies is to develop an orally bioavailable, small-molecule,direct thrombin inhibitor that would be suitable for once or twice daily dosing. An overview of the most advanced peptidomimetic direct thrombin inhibitors bivalirudin, argatroban, ximelagatran and dabigatran is presented. 相似文献
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Design,synthesis, and biological evaluation of 1‐ethyl‐3‐(thiazol‐2‐yl)urea derivatives as Escherichia coli DNA gyrase inhibitors 下载免费PDF全文
Tihomir Tomašič Michaela Barančoková Nace Zidar Janez Ilaš Päivi Tammela Danijel Kikelj 《Archiv der Pharmazie》2018,351(1)
Discovery of novel DNA gyrase B inhibitors remains an attractive field in the search for new antibacterial drugs to overcome the known bacterial resistance mechanisms. In the present study, we designed and synthesized novel ethylurea derivatives of 4,5,6,7‐tetrahydrobenzo[1,2‐d]thiazole‐2,6‐diamine, 2‐(2‐aminothiazol‐4‐yl)acetic acid, and benzo[1,2‐d]thiazole‐2,6‐diamine and evaluated their Escherichia coli DNA gyrase inhibition. The most potent DNA gyrase inhibitors in the prepared library of compounds were benzo[1,2‐d]thiazoles 32–34 , 36 , and 37 with IC50 values in the low micromolar range. The most promising inhibitors identified were evaluated against selected Gram‐positive and Gram‐negative bacterial strains. Compound 33 showed a MIC of 50 μM against an E. coli efflux pump‐defective strain, which suggests that efflux decreases the on‐target concentrations of these compounds. 相似文献
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Uro Urleb Ale Krbav
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Marija Sollner Danijel Kikelj Slavko Pe
ar 《Archiv der Pharmazie》1995,328(2):113-117
The preparation of immunologically active phthalimido desmuramylpeptide analogues 2e-h, 4c-d , and 7b is described. The N-acetylmuramic acid in the muramyl dipeptide has been replaced by a phthaloylated acyclic moiety such as N-phthaloylated amino acids 1a – c , 2-(2-phthalimidoethoxy)acetic acid 3 , or by the carbocyclic rac. trans-2-(2′-phthalimidocyclohexyloxy)acetic acid 6 . 相似文献
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BACKGROUND/AIMS: Intraoperative blood loss is still a major concern for surgeons operating on the liver since it is associated with a significantly higher rate of postoperative complications and shorter long-term survival. An original radiofrequency (RF)-assisted minimal blood loss technique for transecting liver parenchyma is presented. METHODS: In a prospective study, starting November 2001 and ending December 2005, a total of 90 RF-assisted liver resections were done. Pre-cut coagulative desiccation was produced by the Cool-tip (Valleylab, Tyco) water-cooled, single, RF tumor ablation electrode connected to a 480-kHz 200 W generator (Valleylab Cool-tip RF System). Vascular occlusion techniques and low central venous pressure anesthesia were not used. RESULTS: Only 14 (15.5%) patients received blood transfusion (mean transfused blood volume 397 ml; mode 310 ml) and 10 of 14 patients received <310 ml of blood. There was no statistical difference between the patients who underwent major and minor liver resection in frequency of blood transfusion. Blood loss was associated with dense adhesions and difficult liver mobilization and not with liver transection. CONCLUSION: The 'sequential coagulate-cut' RF-assisted liver resection technique is a safe liver transection technique associated with minimal blood loss and it has facilitated tissue-sparing liver resection. 相似文献
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Psychodermatologic disorders are conditions involving an interaction between the mind and the skin. These disorders fall into three major categories: psychosomatic disorders, primary psychiatric disorders and secondary psychiatric disorders (Koo 1995). The treatment of psychodermatologic disorders is almost impossible without a holistic team approach involving psychiatrist, dermatologist and psychologist. Majority of psychodermatologic disorders can be treated with cognitive-bihevioral psychotherapy, psychoterapeutic stress-and-anxiety-management techniques and psychotropic drugs. Psychopharmacologic treatment with anxiolytics, antidepressants, antipsychotics and mood stabilizers can be prescribed by dermatologist, after consulting the psychiatrist. 相似文献
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Marinko P Krbavcic A Mlinsek G Solmajer T Bakija AT Stegnar M Stojan J Kikelj D 《European journal of medicinal chemistry》2004,39(3):257-265
The design, synthesis and biological activity of a series of novel non-covalent D-Phe-Pro-Arg motif-based thrombin inhibitors incorporating 4,5,6,7-tetrahydrobenzothiazol-2-amine as a novel arginine surrogate are described. Compound 9, the most potent in the series of thrombin inhibitors, exhibited an in vitro K(i) of 128 nM and 342-fold selectivity against trypsin. The binding mode of this novel class of thrombin inhibitors in the enzyme active site, based on the X-ray crystal structure of compound 9 co-crystallized with human alpha-thrombin, is discussed. 相似文献
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