Genomes and Genes
Summary: Compounds also known as tetrahydropyridines with general molecular formula (CH2)4NH.
- Camm A, Toft E, Torp Pedersen C, Vijayaraman P, Juul Moller S, Ip J, et al. Efficacy and safety of vernakalant in patients with atrial flutter: a randomized, double-blind, placebo-controlled trial. Europace. 2012;14:804-9 pubmed publisher..Vernakalant did not restore sinus rhythm in patients with AFL. Vernakalant modestly slowed AFL and ventricular response rates, and was well tolerated. ..
- Vaneckova I, Kujal P, Husková Z, Vanourková Z, Vernerova Z, Certíková Chábová V, et al. Effects of combined endothelin A receptor and renin-angiotensin system blockade on the course of end-organ damage in 5/6 nephrectomized Ren-2 hypertensive rats. Kidney Blood Press Res. 2012;35:382-92 pubmed publisher..However, no additive cardio- and renoprotective effects of ET(A) and RAS blockade were noted at the end of the study. ..
- Lukina E, Watman N, Arreguin E, Dragosky M, Iastrebner M, Rosenbaum H, et al. Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment: 2-year results of a phase 2 study. Blood. 2010;116:4095-8 pubmed publisher..No safety-related trends emerged during 2 years of treatment. This multisite, open-label, single-arm phase 2 study is registered at www.clinicaltrials.gov as NCT00358150...
- Filozof C, Gautier J. A comparison of efficacy and safety of vildagliptin and gliclazide in combination with metformin in patients with Type 2 diabetes inadequately controlled with metformin alone: a 52-week, randomized study. Diabet Med. 2010;27:318-26 pubmed publisher..Although both treatments were well tolerated, vildagliptin-treated patients had fewer hypoglycaemic events and did not gain weight. ..
- Derosa G, Ragonesi P, Carbone A, Fogari E, Bianchi L, Bonaventura A, et al. Vildagliptin added to metformin on ?-cell function after a euglycemic hyperinsulinemic and hyperglycemic clamp in type 2 diabetes patients. Diabetes Technol Ther. 2012;14:475-84 pubmed publisher..The addition of vildagliptin to metformin gave a better improvement of glycemic control, insulin resistance, and ?-cell function compared with metformin alone. ..
- Wettwer E, Christ T, Endig S, Rozmaritsa N, Matschke K, Lynch J, et al. The new antiarrhythmic drug vernakalant: ex vivo study of human atrial tissue from sinus rhythm and chronic atrial fibrillation. Cardiovasc Res. 2013;98:145-54 pubmed publisher..Rate-dependent block of Na(+) channels represents the main antiarrhythmic mechanism of vernakalant in the fibrillating atrium. Open channel block of early transient outward currents and IK,ACh could also contribute. ..
- Torp Pedersen C, Raev D, Dickinson G, Butterfield N, Mangal B, Beatch G. A randomized, placebo-controlled study of vernakalant (oral) for the prevention of atrial fibrillation recurrence after cardioversion. Circ Arrhythm Electrophysiol. 2011;4:637-43 pubmed publisher..The absence of proarrhythmia and favorable safety profile is an important finding for the drug. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00526136. ..
- Gerich J. DPP-4 inhibitors: what may be the clinical differentiators?. Diabetes Res Clin Pract. 2010;90:131-40 pubmed publisher..This review offers an overview of DPP-4 inhibitors in T2DM and suggests some characteristics that may provide clinically relevant differentiators within this class. ..
- Goldstein S, Neven P, Cummings S, Colgan T, Runowicz C, Krpan D, et al. Postmenopausal Evaluation and Risk Reduction With Lasofoxifene (PEARL) trial: 5-year gynecological outcomes. Menopause. 2011;18:17-22 pubmed publisher..These findings indicate that 5 years of lasofoxifene treatment result in benign endometrial changes that do not increase the risk for endometrial cancer or hyperplasia in postmenopausal women. ..
- Tian D, Frishman W. Vernakalant: a new drug to treat patients with acute onset atrial fibrillation. Cardiol Rev. 2011;19:41-4 pubmed publisher..Vernakalant appears to be a safe drug to use, with the most common side-effects being dysgeusia, sneezing, paresthesias, nausea, and hypotension. In the clinical trials, there were minimal drug-induced ventricular arrhythmias observed. ..
- Kothny W, Shao Q, Groop P, Lukashevich V. One-year safety, tolerability and efficacy of vildagliptin in patients with type 2 diabetes and moderate or severe renal impairment. Diabetes Obes Metab. 2012;14:1032-9 pubmed publisher..Assess long-term safety and efficacy of the dipeptidlyl peptidase-4 (DPP-4) inhibitor vildagliptin in 369 patients with type 2 diabetes mellitus (T2DM) and moderate or severe renal impairment (RI)...
- He Y, Yamaguchi M, Ito H, Terao S, Sekiguchi K. Pharmacokinetics and pharmacodynamics of vildagliptin in Japanese patients with type 2 diabetes. Int J Clin Pharmacol Ther. 2010;48:582-95 pubmed..Vildagliptin demonstrated similar pharmacokinetic and pharmacodynamic effects in Japanese patients to those observed previously in non-Japanese patients with Type 2 diabetes. ..
- Keating G. Vildagliptin: a review of its use in type 2 diabetes mellitus. Drugs. 2010;70:2089-112 pubmed publisher..In conclusion, vildagliptin is an important option for use in combination with metformin, a sulfonylurea or a thiazolidinedione in patients with type 2 diabetes who require combination therapy. ..
- Pratt C, Roy D, Torp Pedersen C, Wyse D, Toft E, Juul Moller S, et al. Usefulness of vernakalant hydrochloride injection for rapid conversion of atrial fibrillation. Am J Cardiol. 2010;106:1277-83 pubmed publisher..In conclusion, vernakalant demonstrated a rapid and high rate of conversion for short-duration AF and was well tolerated. ..
- Gonzalez A, Benitez D, Tkatchouk E, Goddard W, Toste F. Phosphoramidite gold(I)-catalyzed diastereo- and enantioselective synthesis of 3,4-substituted pyrrolidines. J Am Chem Soc. 2011;133:5500-7 pubmed publisher..A Au(I)-catalyzed synthesis of 3,4-disubstituted pyrrolidines and ?-lactams is described...
- Cialdella P, Pedicino D, Santangeli P. Novel agents for the acute conversion of atrial fibrillation: focus on vernakalant. Recent Pat Cardiovasc Drug Discov. 2011;6:1-8 pubmed..This article will review the recent patents on this novel atrial-selective agent, discussing its mechanisms of action and possible clinical applications in the real-world practice. ..
- Pardanani A, GOTLIB J, Jamieson C, Cortes J, Talpaz M, Stone R, et al. Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis. J Clin Oncol. 2011;29:789-96 pubmed publisher..01); the decrease was durable at 12 months. TG101348 is well tolerated and produces significant reduction in disease burden and durable clinical benefit in patients with myelofibrosis. ..
- Vardarli I, Nauck M, Köthe L, Deacon C, Holst J, Schweizer A, et al. Inhibition of DPP-4 with vildagliptin improved insulin secretion in response to oral as well as "isoglycemic" intravenous glucose without numerically changing the incretin effect in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011;96:945-54 pubmed publisher..Alternatively, yet unidentified mediators of DPP-4 inhibition may have caused these effects. ..
- Saleh M, Boesen E, Pollock J, Savin V, Pollock D. Endothelin receptor A-specific stimulation of glomerular inflammation and injury in a streptozotocin-induced rat model of diabetes. Diabetologia. 2011;54:979-88 pubmed publisher..These observations support the hypothesis that endothelin-1, via the ET(A) receptor, directly increases P(alb), possibly via nephrin loss, as well as early inflammation in the hyperglycaemic rat. ..
- Schweizer A, Dejager S, Foley J, Couturier A, Ligueros Saylan M, Kothny W. Assessing the cardio-cerebrovascular safety of vildagliptin: meta-analysis of adjudicated events from a large Phase III type 2 diabetes population. Diabetes Obes Metab. 2010;12:485-94 pubmed publisher..In a large meta-analysis, vildagliptin was not associated with an increased risk of adjudicated CCV events relative to all comparators in the broad population of type 2 diabetes including patients at increased risk of CCV events. ..
- Tian J, Ho I, Tsou H, Fang C, Hsiao C, Chen C, et al. UGT2B7 genetic polymorphisms are associated with the withdrawal symptoms in methadone maintenance patients. Pharmacogenomics. 2012;13:879-88 pubmed publisher..008). Haplotypes of GATCAGCCGC and CTCTGATTCT were significantly associated with pupil size score and tremor score (p < 0.034). These results suggest that SNPs of the UGT2B7 gene may play important roles in opiate withdrawal symptoms. ..
- Foley J, Jordan J. Weight neutrality with the DPP-4 inhibitor, vildagliptin: mechanistic basis and clinical experience. Vasc Health Risk Manag. 2010;6:541-8 pubmed..Elaboration of these and other pathways could further clarify the origins of the favorable weight profile of vildagriptin. ..
- Hassanein M, Hanif W, Malik W, Kamal A, Geransar P, Lister N, et al. Comparison of the dipeptidyl peptidase-4 inhibitor vildagliptin and the sulphonylurea gliclazide in combination with metformin, in Muslim patients with type 2 diabetes mellitus fasting during Ramadan: results of the VECTOR study. Curr Med Res Opin. 2011;27:1367-74 pubmed publisher..When extrapolated to the global Muslim population with a similar clinical background, these findings could have considerable public health and clinical implications. ..
- Yin M, Sillje H, Meissner M, van Gilst W, de Boer R. Early and late effects of the DPP-4 inhibitor vildagliptin in a rat model of post-myocardial infarction heart failure. Cardiovasc Diabetol. 2011;10:85 pubmed publisher..Vildagliptin increases the active GLP-1 level via inhibition of DPP-4, but it has no substantial protective effects on cardiac function in this well established long-term post-MI cardiac remodeling model. ..
- Derosa G, Ragonesi P, Carbone A, Fogari E, D Angelo A, Cicero A, et al. Vildagliptin action on some adipocytokine levels in type 2 diabetic patients: a 12-month, placebo-controlled study. Expert Opin Pharmacother. 2012;13:2581-91 pubmed publisher..Vildagliptin + metformin also decreased resistin, RBP-4, and chemerin better. Vildagliptin seems to have a positive action on some adipocytokines related to inflammation. ..
- Zajdel P, Kurczab R, Grychowska K, Satała G, Pawłowski M, Bojarski A. The multiobjective based design, synthesis and evaluation of the arylsulfonamide/amide derivatives of aryloxyethyl- and arylthioethyl- piperidines and pyrrolidines as a novel class of potent 5-HT? receptor antagonists. Eur J Med Chem. 2012;56:348-60 pubmed publisher..library of the arylamide and arylsulfonamide derivatives of aryloxyethyl- and arylthioethyl- piperidines and pyrrolidines. All compounds 24-95 were synthesized according to an elaborated parallel solid-phase method and were ..
- Guerci B, Monnier L, Serusclat P, Petit C, Valensi P, Huet D, et al. Continuous glucose profiles with vildagliptin versus sitagliptin in add-on to metformin: results from the randomized Optima study. Diabetes Metab. 2012;38:359-66 pubmed publisher..However, vildagliptin induced better circadian glycaemic control than sitagliptin with a significant decrease on overall hyperglycemia, mainly driven by reduction on basal hyperglycaemia. ..
- Mai D, Wolfe J. Asymmetric palladium-catalyzed carboamination reactions for the synthesis of enantiomerically enriched 2-(arylmethyl)- and 2-(alkenylmethyl)pyrrolidines. J Am Chem Soc. 2010;132:12157-9 pubmed publisher..The application of this method to a concise asymmetric synthesis of (-)-tylophorine is also discussed. ..
- Terasaki M, Nagashima M, Watanabe T, Nohtomi K, Mori Y, Miyazaki A, et al. Effects of PKF275-055, a dipeptidyl peptidase-4 inhibitor, on the development of atherosclerotic lesions in apolipoprotein E-null mice. Metabolism. 2012;61:974-7 pubmed publisher..Foam cell formation was suppressed by 40% in the exudate peritoneal macrophages obtained from the PKF-treated mice. The DPP-4 inhibitor prevents the development of atherosclerotic lesions by suppressing macrophage foam cell formation...
- Matthews D, Dejager S, Ahren B, Fonseca V, Ferrannini E, Couturier A, et al. Vildagliptin add-on to metformin produces similar efficacy and reduced hypoglycaemic risk compared with glimepiride, with no weight gain: results from a 2-year study. Diabetes Obes Metab. 2010;12:780-9 pubmed publisher..001]. Overall, both treatments were well tolerated and displayed similar safety profiles. Vildagliptin add-on has similar efficacy to glimepiride after 2 years' treatment, with markedly reduced hypoglycaemia risk and no weight gain. ..
- Derosa G, Maffioli P, Ferrari I, Mereu R, Ragonesi P, Querci F, et al. Effects of one year treatment of vildagliptin added to pioglitazone or glimepiride in poorly controlled type 2 diabetic patients. Horm Metab Res. 2010;42:663-9 pubmed publisher..Pioglitazone plus vildagliptin were found to be more effective in preserving beta-cell function, and in reducing insulin resistance, and inflammatory state parameters. ..
- Li H, Kim W, Guillemin G, Hill A, Evin G, Garner B. Modulation of amyloid precursor protein processing by synthetic ceramide analogues. Biochim Biophys Acta. 2010;1801:887-95 pubmed publisher..In conclusion, this study provides novel information regarding the regulation of APP processing by synthetic ceramide analogues and reveals that the most potent of these compounds is EtDO-P4. ..
- James N, Caty A, Payne H, Borre M, Zonnenberg B, Beuzeboc P, et al. Final safety and efficacy analysis of the specific endothelin A receptor antagonist zibotentan (ZD4054) in patients with metastatic castration-resistant prostate cancer and bone metastases who were pain-free or mildly symptomatic for pain: a double-b. BJU Int. 2010;106:966-73 pubmed publisher..To confirm the survival signal observed in the present study, zibotentan is being investigated further in the ENdoTHelin A USE (ENTHUSE) Phase III clinical trial programme. ..
- Duggan S, Scott L. Intravenous vernakalant: a review of its use in the management of recent-onset atrial fibrillation. Drugs. 2011;71:237-52 pubmed publisher..Therefore, intravenous vernakalant provides an effective option for the management of recent-onset atrial fibrillation. ..
- Duttaroy A, Voelker F, Merriam K, Zhang X, Ren X, Subramanian K, et al. The DPP-4 inhibitor vildagliptin increases pancreatic beta cell mass in neonatal rats. Eur J Pharmacol. 2011;650:703-7 pubmed publisher..This study demonstrates that DPP-4 inhibitors can elicit beneficial effects on beta cell turnover that could help to prevent or retard the progression of type 2 diabetes. ..
- Guo Q, Feng L, Liu M, Zhang Y, Chai Y, Lv K, et al. Synthesis and in vitro antibacterial activity of fluoroquinolone derivatives containing 3-(N'-alkoxycarbamimidoyl)-4-(alkoxyimino) pyrrolidines. Eur J Med Chem. 2010;45:5498-506 pubmed publisher..In addition, compound 33 is 32 and 16-32 fold more potent than both the reference drugs against Enterococcus faecium 08-7 and Klebsiella pneumoniae 09-22, respectively. ..
- Schweizer A, Dejager S, Foley J, Shao Q, Kothny W. Clinical experience with vildagliptin in the management of type 2 diabetes in a patient population ?75 years: a pooled analysis from a database of clinical trials. Diabetes Obes Metab. 2011;13:55-64 pubmed publisher..2 vs. 7.5 events per 100 SYE, respectively). The safety profile of vildagliptin was overall similar in younger and older patients. Vildagliptin was effective and well-tolerated in type 2 diabetic patients ?75 years (mean age 77 years). ..
- Ensrud K, LaCroix A, Thompson J, Thompson D, Eastell R, Reid D, et al. Lasofoxifene and cardiovascular events in postmenopausal women with osteoporosis: Five-year results from the Postmenopausal Evaluation and Risk Reduction with Lasofoxifene (PEARL) trial. Circulation. 2010;122:1716-24 pubmed publisher..5 mg/d was due primarily to lower risks of coronary revascularization procedures, hospitalization for unstable angina, and diagnosis of new ischemic heart disease. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00141323. ..
- Vernaleken I, Peters L, Raptis M, Lin R, Buchholz H, Zhou Y, et al. The applicability of SRTM in [(18)F]fallypride PET investigations: impact of scan durations. J Cereb Blood Flow Metab. 2011;31:1958-66 pubmed publisher..Apparently, the D(2/3) receptor occupancy results of APs, especially preferential extrastriatal binding observations, are not relevantly biased by inappropriate scan durations. ..
- Foley J, Bunck M, Möller Goede D, Poelma M, Nijpels G, Eekhoff E, et al. Beta cell function following 1 year vildagliptin or placebo treatment and after 12 week washout in drug-naive patients with type 2 diabetes and mild hyperglycaemia: a randomised controlled trial. Diabetologia. 2011;54:1985-91 pubmed publisher..This effect was not maintained after the washout, indicating that this increased capacity was not a disease modifying effect on beta cell mass and/or function. ClinicalTrials.gov NCT00260156. ..
- Fakhoury W, LeReun C, Wright D. A meta-analysis of placebo-controlled clinical trials assessing the efficacy and safety of incretin-based medications in patients with type 2 diabetes. Pharmacology. 2010;86:44-57 pubmed publisher..30-4.11, p = 0.002). Incretin-based therapies are effective in glycemic control and also offer other advantages such as weight loss (exenatide and liraglutide). This may have an important impact on patient adherence to medication. ..
- Stiell I, Dickinson G, Butterfield N, Clement C, Perry J, Vaillancourt C, et al. Vernakalant hydrochloride: A novel atrial-selective agent for the cardioversion of recent-onset atrial fibrillation in the emergency department. Acad Emerg Med. 2010;17:1175-82 pubmed publisher..Vernakalant rapidly converted recent-onset AF to sinus rhythm in over half of patients, was well tolerated, and has the potential to offer an important therapeutic option for rhythm control of recent-onset AF in the ED. ..
- Lemen G, Wolfe J. Pd-catalyzed carboamination of oxazolidin-2-ones: a stereoselective route to trans-2,5-disubstituted pyrrolidines. Org Lett. 2010;12:2322-5 pubmed publisher..transformations afford bicyclic oxazolidin-2-one derivatives that can be converted to trans-2,5-disubstituted pyrrolidines in one step...