Genomes and Genes
Summary: Compounds with a BENZENE fused to IMIDAZOLES.
- Yuan Y, Wang Q, Paulk J, Kubicek S, Kemp M, Adams D, et al. A small-molecule probe of the histone methyltransferase G9a induces cellular senescence in pancreatic adenocarcinoma. ACS Chem Biol. 2012;7:1152-7 pubmed publisher..ATM-pathway activation, caused by either genetic or small-molecule inhibition of G9a, may mediate BRD4770-induced cell senescence. BRD4770 may be a useful tool to study G9a and its role in senescence and cancer cell biology. ..
- Lentz C, Stumpfe D, Bajorath J, Famulok M, Hoerauf A, Pfarr K. New chemotypes for wALADin1-like inhibitors of delta-aminolevulinic acid dehydratase from Wolbachia endobacteria. Bioorg Med Chem Lett. 2013;23:5558-62 pubmed publisherSubstituted benzimidazoles of the wALADin1-family have recently been identified as a new class of species-selective inhibitors of delta-aminolevulinic acid dehydratase (ALAD) from Wolbachia endobacteria of parasitic filarial worms...
- Min L, Mogi M, Shudou M, Jing F, Tsukuda K, Ohshima K, et al. Peroxisome proliferator-activated receptor-? activation with angiotensin II type 1 receptor blockade is pivotal for the prevention of blood-brain barrier impairment and cognitive decline in type 2 diabetic mice. Hypertension. 2012;59:1079-88 pubmed publisher
- Wanek M, Horn E, Elapavaluru S, Baroody S, Sokos G. Safe use of hemodialysis for dabigatran removal before cardiac surgery. Ann Pharmacother. 2012;46:e21 pubmed publisher..The routine use of preoperative hemodialysis in patients on dabigatran is not recommended; however, the potential efficacy in such circumstances is supported by the successful results in this case. ..
- Zhu D, Bays H, Gao P, Mattheus M, Voelker B, Ruilope L. Efficacy and tolerability of initial therapy with single-pill combination telmisartan/hydrochlorothiazide 80/25 mg in patients with grade 2 or 3 hypertension: a multinational, randomized, double-blind, active-controlled trial. Clin Ther. 2012;34:1613-24 pubmed publisher..Both treatments appeared to be well tolerated. ..
- Spannagl M, Bauersachs R, Debus E, Gawaz M, Gerlach H, Haas S, et al. [Dabigatran therapy--perioperative management and interpretation of coagulation tests]. Hamostaseologie. 2012;32:294-305 pubmed publisher..A distinct feature of dabigatran is the possibility of effectively removing dabigatran from the circulation by haemodialysis...
- Eriksson B, Smith J, Caprini J, Hantel S, Clemens A, Feuring M, et al. Evaluation of the acute coronary syndrome safety profile of dabigatran etexilate in patients undergoing major orthopedic surgery: findings from four Phase 3 trials. Thromb Res. 2012;130:396-402 pubmed publisher..None of these between-group differences were statistically significant. No increased ACS signal was detected with dabigatran etexilate compared with enoxaparin during or after treatment. ..
- Healey J, Eikelboom J, Douketis J, Wallentin L, Oldgren J, Yang S, et al. Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) randomized trial. Circulation. 2012;126:343-8 pubmed publisher..Dabigatran reduces ischemic stroke in comparison with warfarin; however, given the lack of antidote, there is concern that it might increase bleeding when surgery or invasive procedures are required...
- Aguayo Ortiz R, Méndez Lucio O, Medina Franco J, Castillo R, Yepez Mulia L, Hernández Luis F, et al. Towards the identification of the binding site of benzimidazoles to ?-tubulin of Trichinella spiralis: insights from computational and experimental data. J Mol Graph Model. 2013;41:12-9 pubmed publisher..These results constitute valuable information for the design or improvement of more potent and selective molecules...
- Kjeldsen S, Schumacher H, Neldam S, Guthrie R. Telmisartan/Hydrochlorothiazide combination therapy for the treatment of hypertension: a pooled analysis in older and younger patients. J Clin Hypertens (Greenwich). 2013;15:380-8 pubmed publisher..The telmisartan/hydrochlorothiazide combination, particularly high-dose T80/H25, is effective and well tolerated in patients 65 years and older as well as in younger patients. ..
- Shiota A, Shimabukuro M, Fukuda D, Soeki T, Sato H, Uematsu E, et al. Telmisartan ameliorates insulin sensitivity by activating the AMPK/SIRT1 pathway in skeletal muscle of obese db/db mice. Cardiovasc Diabetol. 2012;11:139 pubmed publisher..Here, we investigated the pathways through which telmisartan acts on skeletal muscle, in vitro as well as in vivo...
- Kadoglou N, Moustardas P, Katsimpoulas M, Kapelouzou A, Kostomitsopoulos N, Schafer K, et al. The beneficial effects of a direct thrombin inhibitor, dabigatran etexilate, on the development and stability of atherosclerotic lesions in apolipoprotein E-deficient mice : dabigatran etexilate and atherosclerosis. Cardiovasc Drugs Ther. 2012;26:367-74 pubmed publisher..The plaque-stabilizing effects of chronic thrombin inhibition might be the result of the favorable modification of inflammatory mechanisms. ..
- Schiele F, van Ryn J, Canada K, Newsome C, Sepulveda E, Park J, et al. A specific antidote for dabigatran: functional and structural characterization. Blood. 2013;121:3554-62 pubmed publisher..This is the first report of a specific antidote for a next-generation anticoagulant that may become a valuable tool in patients who require emergency procedures. ..
- Huang C, Siu M, Vu L, Wong S, Shin J. Factors influencing doctors' selection of dabigatran in non-valvular atrial fibrillation. J Eval Clin Pract. 2013;19:938-43 pubmed publisher..Safety and effectiveness of dabigatran as well as patient preference were additional factors influencing their decision. General internists were less comfortable with prescribing dabigatran than cardiologists. ..
- Lambourne M, Eltringham Smith L, Gataiance S, Arnold D, Crowther M, Sheffield W. Prothrombin complex concentrates reduce blood loss in murine coagulopathy induced by warfarin, but not in that induced by dabigatran etexilate. J Thromb Haemost. 2012;10:1830-40 pubmed publisher..Our data suggest that PCC treatment prevents excess bleeding much more effectively in warfarin-induced coagulopathy than in DE-induced coagulopathy. ..
- Pragst I, Zeitler S, Doerr B, Kaspereit F, Herzog E, Dickneite G, et al. Reversal of dabigatran anticoagulation by prothrombin complex concentrate (Beriplex P/N) in a rabbit model. J Thromb Haemost. 2012;10:1841-8 pubmed publisher..89; CI, 1.64-5.09). In this animal study, PCC showed potential as an agent for reversing the effects of dabigatran. Further investigation is warranted. ..
- Snipelisky D, Kauffman C, Prussak K, Johns G, Venkatachalam K, Kusumoto F. A comparison of bleeding complications post-ablation between warfarin and dabigatran. J Interv Card Electrophysiol. 2012;35:29-33 pubmed publisher..In our cohort, bleeding-related complications 48 h and 1 week post-ablation were similar for warfarin and dabigatran. Dabigatran is associated with more intraprocedural variability in ACT than warfarin. ..
- Guo Z, Zhang R, Li J, Xu G. Effect of telmisartan on the expression of adiponectin receptors and nicotinamide adenine dinucleotide phosphate oxidase in the heart and aorta in type 2 diabetic rats. Cardiovasc Diabetol. 2012;11:94 pubmed publisher..Telmisartan also induces a protective role on the vascular system by upregulating the expression of adipoR1 and downregulating the expression of MCP-1 and NF-?B in the abdominal aorta in diabetic rats. ..
- Larsen T, Rasmussen L, Skjøth F, Due K, Callréus T, Rosenzweig M, et al. Efficacy and safety of dabigatran etexilate and warfarin in "real-world" patients with atrial fibrillation: a prospective nationwide cohort study. J Am Coll Cardiol. 2013;61:2264-73 pubmed publisher..We found no evidence of an excess of bleeding events or MI among dabigatran-treated patients in this propensity-matched comparison against warfarin, even in the subgroup with ?1-year follow-up. ..
- Angevin E, López Martín J, Lin C, Gschwend J, Harzstark A, Castellano D, et al. Phase I study of dovitinib (TKI258), an oral FGFR, VEGFR, and PDGFR inhibitor, in advanced or metastatic renal cell carcinoma. Clin Cancer Res. 2013;19:1257-68 pubmed publisher..Here, dovitinib (TKI258), a potent oral inhibitor of FGF receptor, VEGF receptor (VEGFR), and platelet-derived growth factor receptor tyrosine kinases, is studied in a dose escalation trial...
- Van de Werf F, Brueckmann M, Connolly S, Friedman J, Granger C, Hartter S, et al. A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves: THE Randomized, phase II study to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients after heart valve replacement (RE-ALIGN). Am Heart J. 2012;163:931-937.e1 pubmed publisher..RE-ALIGN is the first study to test an alternative to warfarin in patients with mechanical heart valves. A definitive phase III study will be planned based on the results of this study. ..
- Nagarakanti R, Ellis C. Dabigatran in clinical practice. Clin Ther. 2012;34:2051-60 pubmed publisher..Our effort should facilitate the safe and effective use of dabigatran in atrial fibrillation. ..
- Mantha S, Ansell J. An indirect comparison of dabigatran, rivaroxaban and apixaban for atrial fibrillation. Thromb Haemost. 2012;108:476-84 pubmed publisher..Such an indirect comparison should be used only to generate hypotheses which need to be tested in a dedicated randomised trial comparing the three drugs directly...
- Ley L, Schumacher H. Telmisartan plus amlodipine single-pill combination for the management of hypertensive patients with a metabolic risk profile (added-risk patients). Curr Med Res Opin. 2013;29:41-53 pubmed publisher..This combination is also well tolerated, and may be considered a suitable option for these added-risk hypertensive patients. ..
- Dong L, Huang J, Qu C, Zhang Q, Zhang W, Han B, et al. Rhodium(III)-catalyzed vinylic sp2 C-H bond functionalization: efficient synthesis of pyrido[1,2-?]benzimidazoles and imidazo[1,2-?]pyridines. Org Biomol Chem. 2013;11:6142-9 pubmed publisherA simple approach for synthesis of novel aza-fused scaffolds such as pyrido[1,2-?]benzimidazoles and imidazo[1,2-?]pyridines was developed by Rh(III)-catalyzed direct oxidative coupling between alkenes and unactivated alkynes without an ..
- Fagan V, Bonham S, Carty M, Saenz Méndez P, Eriksson L, Aldabbagh F. COMPARE analysis of the toxicity of an iminoquinone derivative of the imidazo[5,4-f]benzimidazoles with NAD(P)H:quinone oxidoreductase 1 (NQO1) activity and computational docking of quinones as NQO1 substrates. Bioorg Med Chem. 2012;20:3223-32 pubmed publisher..Docking also indicated that the presence of a substituent capable of hydrogen bonding to the His194 residue is important in influencing the orientation of the substrate in the NQO1 active site, leading to more efficient reduction. ..
- Nin T, Sairaku A, Yoshida Y, Kamiya H, Tatematsu Y, Nanasato M, et al. A randomized controlled trial of dabigatran versus warfarin for periablation anticoagulation in patients undergoing ablation of atrial fibrillation. Pacing Clin Electrophysiol. 2013;36:172-9 pubmed publisher..An anticoagulation strategy with dabigatran may surpass that with warfarin in reducing both the periprocedural risk of minor bleeding and a hypercoagulable state, and the time to ablation in patients undergoing ablation of AF. ..
- Bansal Y, Silakari O. The therapeutic journey of benzimidazoles: a review. Bioorg Med Chem. 2012;20:6208-36 pubmed publisher..This discussion will further help in the development of novel benzimidazole compounds. ..
- Kaseno K, Naito S, Nakamura K, Sakamoto T, Sasaki T, Tsukada N, et al. Efficacy and safety of periprocedural dabigatran in patients undergoing catheter ablation of atrial fibrillation. Circ J. 2012;76:2337-42 pubmed..9%; P<0.05). ?Dabigatran at a dose of 110mg twice daily was safe for AF ablation in patients with a relatively low risk of thromboemboli, suggesting that it may become an alternative to warfarin in those patients. ..
- Ascierto P, Schadendorf D, Berking C, Agarwala S, van Herpen C, Queirolo P, et al. MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study. Lancet Oncol. 2013;14:249-56 pubmed publisher..To our knowledge, MEK162 is the first targeted therapy to show activity in patients with NRAS -mutated melanoma and might offer a new option for a cancer with few effective treatments. Novartis Pharmaceuticals. ..
- Sakamoto M, Suzuki H, Hayashi T, Iuchi H, Isaka T, Sakamoto N, et al. Effects of candesartan in hypertensive patients with type 2 diabetes mellitus on inflammatory parameters and their relationship to pulse pressure. Cardiovasc Diabetol. 2012;11:118 pubmed publisher..Patients with pulse pressure <60?mmHg might receive protective benefits by candesartan. UMIN000007921. ..
- Lucero M, Patterson A. Whole-body tissue distribution of total radioactivity in rats after oral administration of [¹?C]-bilastine. Drug Chem Toxicol. 2012;35 Suppl 1:1-7 pubmed publisher..In time-mated female rats, but not in albino or pigmented male rats, there was evidence of low-level passage of radioactivity across the placental barrier into fetal tissues as well as low-level transfer of radioactivity into the brain. ..
- Kansal A, Sharma M, Bradley Kennedy C, Clemens A, Monz B, Peng S, et al. Dabigatran versus rivaroxaban for the prevention of stroke and systemic embolism in atrial fibrillation in Canada. Comparative efficacy and cost-effectiveness. Thromb Haemost. 2012;108:672-82 pubmed..This study found dabigatran is economically dominant versus rivaroxaban for prevention of stroke and systemic embolism among Canadian AF patients. ..
- Neldam S, Schumacher H, Guthrie R. Telmisartan 80 mg/hydrochlorothiazide 25 mg provides clinically relevant blood pressure reductions across baseline blood pressures. Adv Ther. 2012;29:327-38 pubmed publisher..Combination treatment of telmisartan and hydrochlorothiazide results in large and clinically relevant BP reductions additional to those provided by monotherapy. ..
- Schulman S, Kearon C, Kakkar A, Schellong S, Eriksson H, Baanstra D, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013;368:709-18 pubmed publisher..Dabigatran, which is administered in a fixed dose and does not require laboratory monitoring, may be suitable for extended treatment of venous thromboembolism...
- Lucero M, Gonzalo A, Mumford R, Betanzos M, Alejandro A. An overview of bilastine metabolism during preclinical investigations. Drug Chem Toxicol. 2012;35 Suppl 1:18-24 pubmed publisher..These characteristics demonstrate the potential for bilastine to be a good choice for allergic patients receiving treatment for other concomitant diseases, including those with renal or hepatic dysfunction. ..
- Brooks M, Neelam S, Fudala R, Gryczynski I, Cammarata P. Lenticular mitoprotection. Part A: Monitoring mitochondrial depolarization with JC-1 and artifactual fluorescence by the glycogen synthase kinase-3? inhibitor, SB216763. Mol Vis. 2013;19:1406-12 pubmed..We conclude that inhibition of GSK-3? activity by the GSK-3? inhibitor SB216763 provides positive protection against mitochondrial depolarization. ..
- Vranckx P, Verheugt F, de Maat M, Ulmans V, Regar E, Smits P, et al. A randomised study of dabigatran in elective percutaneous coronary intervention in stable coronary artery disease patients. EuroIntervention. 2013;8:1052-60 pubmed publisher..One minor access-site bleeding occurred in the dabigatran group. Dabigatran treatment (110 mg or 150 mg BID) may not provide sufficient anticoagulation during PCI. EudraCT. No: 2007-007536-25. ..
- Kirley K, Qato D, Kornfield R, Stafford R, Alexander G. National trends in oral anticoagulant use in the United States, 2007 to 2011. Circ Cardiovasc Qual Outcomes. 2012;5:615-21 pubmed..We did not find evidence that it has increased overall atrial fibrillation treatment rates. ..
- ..e. cetirizine, levocetirizine and desloratadine). Bilastine was generally well tolerated, with a tolerability profile that was generally similar to that of the other second-generation antihistamines included in phase III clinical trials. ..
- Halbmayer W, Weigel G, Quehenberger P, Tomasits J, Haushofer A, Aspoeck G, et al. Interference of the new oral anticoagulant dabigatran with frequently used coagulation tests. Clin Chem Lab Med. 2012;50:1601-5 pubmed publisher..This finding might become particularly important in the elderly and in patients with renal impairment as well as patients whose blood is drawn at peak levels of dabigatran. ..
- Davidson T, Husberg M, Janzon M, Oldgren J, Levin L. Cost-effectiveness of dabigatran compared with warfarin for patients with atrial fibrillation in Sweden. Eur Heart J. 2013;34:177-83 pubmed publisher..Dabigatran is a cost-effective treatment in Sweden, as its incremental cost-effectiveness ratio is below the normally accepted willingness to pay limit. ..
- Lee V, Conners J, Prabhakaran S. Intravenous thrombolysis in a stroke patient taking dabigatran. J Stroke Cerebrovasc Dis. 2012;21:916.e11-2 pubmed publisher..Although aPTT does not provide a linear response to dabigatran therapy, the presence of a completely normal PTT may exclude therapeutic dabigatran anticoagulation. ..
- Marlu R, Hodaj E, Paris A, Albaladejo P, Cracowski J, Crackowski J, et al. Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thromb Haemost. 2012;108:217-24 pubmed publisher..However, clinical evaluation is needed regarding haemorrhagic situations, and a meticulous risk-benefit evaluation regarding their use in this context is required. ..
- Khadzhynov D, Wagner F, Formella S, Wiegert E, Moschetti V, Slowinski T, et al. Effective elimination of dabigatran by haemodialysis. A phase I single-centre study in patients with end-stage renal disease. Thromb Haemost. 2013;109:596-605 pubmed publisher..There was a clinically negligible redistribution of dabigatran after haemodialysis. These results demonstrate that haemodialysis can be a suitable approach to eliminate dabigatran in emergency situations. ..
- Wang X, Kay A, Anak O, Angevin E, Escudier B, Zhou W, et al. Population pharmacokinetic/pharmacodynamic modeling to assist dosing schedule selection for dovitinib. J Clin Pharmacol. 2013;53:14-20 pubmed publisher..Furthermore, dovitinib was well tolerated, and antitumor activity was observed as well in this new study. The 5-days-on/2-days-off dosing schedule is currently used in a dovitinib registration trial and other clinical trials. ..
- Xia X, Wang Y, Wang X, Li Y, Zhong F, Li X, et al. Validation of a method for simultaneous determination of nitroimidazoles, benzimidazoles and chloramphenicols in swine tissues by ultra-high performance liquid chromatography-tandem mass spectrometry. J Chromatogr A. 2013;1292:96-103 pubmed publisher..method for the analysis of 23 veterinary drugs and metabolites belonging to three classes (nitroimidazoles, benzimidazoles, and chloramphenicols) in porcine muscle, liver, and kidney...
- Lentz C, Halls V, Hannam J, Niebel B, Strübing U, Mayer G, et al. A selective inhibitor of heme biosynthesis in endosymbiotic bacteria elicits antifilarial activity in vitro. Chem Biol. 2013;20:177-87 pubmed publisher..Our findings validate wALADins as a basis for developing potent leads that meet current requirements for antifilarial drugs. ..
- Noh Y, Lim H, Kim M, Kim Y, Choi H, Sung H, et al. Pharmacokinetic interaction of telmisartan with s-amlodipine: an open-label, two-period crossover study in healthy Korean male volunteers. Clin Ther. 2012;34:1625-35 pubmed publisher..Both formulations were generally well-tolerated. ..
- Lee I, Kratz M, Schirmer S, Baumhakel M, Bohm M. The effects of direct thrombin inhibition with dabigatran on plaque formation and endothelial function in apolipoprotein E-deficient mice. J Pharmacol Exp Ther. 2012;343:253-7 pubmed publisher..Interference with the coagulation system might provide a therapeutic target to modify atherosclerotic disease progression. ..
- Dans A, Connolly S, Wallentin L, Yang S, Nakamya J, Brueckmann M, et al. Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Circulation. 2013;127:634-40 pubmed publisher..URL: http://clinicaltrials.gov. Unique identifier: NCT00262600. ..
- McKeage K. Dabigatran etexilate: a pharmacoeconomic review of its use in the prevention of stroke and systemic embolism in patients with atrial fibrillation. Pharmacoeconomics. 2012;30:841-55 pubmed publisher..However, the incremental cost per QALY gained for dabigatran versus warfarin improved when levels of international normalized ratio control in warfarin recipients decreased and when the baseline level of risk of stroke increased. ..
- Pang T, Wang J, Benicky J, SÃ¡nchez Lemus E, Saavedra J. Telmisartan directly ameliorates the neuronal inflammatory response to IL-1Î² partly through the JNK/c-Jun and NADPH oxidase pathways. J Neuroinflammation. 2012;9:102 pubmed publisher..Our results support the hypothesis that AT1 receptor blockers are directly neuroprotective, and should be considered for the treatment of inflammatory conditions of the brain. ..
- Antoniou T, Camacho X, Yao Z, Gomes T, Juurlink D, Mamdani M. Comparative effectiveness of angiotensin-receptor blockers for preventing macrovascular disease in patients with diabetes: a population-based cohort study. CMAJ. 2013;185:1035-41 pubmed publisher..Telmisartan and valsartan may therefore be the preferred angiotensin-receptor blockers for use in these patients. ..
- Villapol S, Yaszemski A, Logan T, Sanchez Lemus E, Saavedra J, Symes A. Candesartan, an angiotensin II AT?-receptor blocker and PPAR-? agonist, reduces lesion volume and improves motor and memory function after traumatic brain injury in mice. Neuropsychopharmacology. 2012;37:2817-29 pubmed publisher..Overall, our data suggest that ARBs with dual AT?R-blocking and PPAR? activation properties may have therapeutic value in treating TBI. ..
- Yang Y, Zhi F, He X, Moore M, Kang X, Chao D, et al. ?-opioid receptor activation and microRNA expression of the rat cortex in hypoxia. PLoS ONE. 2012;7:e51524 pubmed publisher..DOR activation can modify, enhance or resolve the changes in miRNAs that target HIF, ion transport, axonal guidance, free radical signaling, apoptosis and many other functions. ..
- Mori H, Okada Y, Arao T, Nishida K, Tanaka Y. Telmisartan at 80 mg/day increases high-molecular-weight adiponectin levels and improves insulin resistance in diabetic patients. Adv Ther. 2012;29:635-44 pubmed publisher..In diabetic patients with hypertension, high-dose telmisartan increased HMW adiponectin levels and improved insulin resistance through activation of PPAR-gamma. ..
- Cheng J, Vu H. Dabigatran etexilate: an oral direct thrombin inhibitor for the management of thromboembolic disorders. Clin Ther. 2012;34:766-87 pubmed publisher..The relative ease of oral administration, no need for routine monitoring, and lack of significant drug interactions, may favor use of DE over other anticoagulants. However, there is no antidote for DE currently available. ..