Search results for "Triazole"

Reaction of 3-Amino-1,2,4-Triazole with Diethyl Phosphite and Triethyl Orthoformate: Acid-Base Properties and Antiosteoporotic Activities of the Prod…

2017

The reaction of diethyl phosphite with triethyl orthoformate and a primary amine followed by hydrolysis is presented, and the reaction was suitable for the preparation of (aminomethylene)bisphosphonates. 3-Amino-1,2,4-triazole was chosen as an interesting substrate for this reaction because it possesses multiple groups that can serve as the amino component in the reaction-namely, the side-chain and triazole amines. This substrate readily forms 1,2,4-triazolyl-3-yl-aminomethylenebisphosphonic acid (compound 1) as a major product, along with N-ethylated bisphosphonates as side products. The in vitro antiproliferative effects of the synthesized aminomethylenebisphosphonic acids against J774E m…

Synthesis, structure and properties of N-acetylated derivatives of methyl 5-amino-1H-[1,2,4]triazole-3-carboxylate.

2004

Methyl 5-amino-1H-[1,2,4]triazole-3-carboxylate hydrochloride (1). and free ester (2). were obtained and 2 was reacted with Ac(2)O to give the acetylated products 3-6. Compounds 1-6 were studied using HPLC, GC-MS, FTIR and multinuclear NMR spectroscopy, including the cross-polarisation magic angle spinning (CPMAS) technique. The results of the acetylation of 2 were compared to those of the acetylation of 5-amino-1H-[1,2,4]triazole, and for 2 a significant decrease in the susceptibility to acetylation was found. The reaction of 2 with Ac(2)O at 20 degrees C, regardless of the amount and the concentration of the latter, including neat Ac(2)O, proceeds fully regioselectively and leads to one p…

Calculation of binding energy using BLYP/MM for the HIV-1 integrase complexed with the S-1360 and two analogues.

2007

Abstract Integrase (IN) is one of the three human immunodeficiency virus type 1 (HIV-1) enzymes essential for effective viral replication. S-1360 is a potent and selective inhibitor of HIV-1 IN. In this work, we have carried out molecular dynamics (MD) simulations using a hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) approach, to determine the protein–ligand interaction energy for S-1360 and two analogues. Analysis of the MD trajectories reveals that the strongest protein–inhibitor interactions, observed in the three studied complexes, are established with Lys-159 residue and Mg 2+ cation. Calculations of binding energy using BLYP/MM level of theory reveal that there is a direct rela…

Synthesis of Azole-Heterocycles as Potential Antitumor and/or Antiviral Agents

2014

Impact of glucuronide interferences on therapeutic drug monitoring of posaconazole by tandem mass spectrometry.

2010

Abstract Background: Posaconazole is a novel antifungal drug for oral application intended especially for therapy of invasive mycoses. Due to variable gastrointestinal absorption, adverse side effects, and suspected drug-drug interactions, therapeutic drug monitoring (TDM) of posaconazole is recommended. Method: A fast ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for quantification of posaconazole with a run-time <3 min was developed and compared to a LC-MS/MS method and HPLC method with fluorescence detection. Results: During evaluation of UPLC-MS/MS, two earlier eluting peaks were observed in the MRM trace of posaconazole. This was only seen in p…

The EndoPredict score provides prognostic information on late distant metastases in ER+/HER2− breast cancer patients

2013

Background: ER þ/HER2 � breast cancers have a proclivity for late recurrence. A personalised estimate of relapse risk after 5 years of endocrine treatment can improve patient selection for extended hormonal therapy. Methods: A total of 1702 postmenopausal ER þ/HER2 � breast cancer patients from two adjuvant phase III trials (ABCSG6, ABCSG8) treated with 5 years of endocrine therapy participated in this study. The multigene test EndoPredict (EP) and the EPclin score (which combines EP with tumour size and nodal status) were predefined in independent training cohorts. All patients were retrospectively assigned to risk categories based on gene expression and on clinical parameters. The primary…

A polymorphism at the 3'-UTR region of the aromatase gene defines a subgroup of postmenopausal breast cancer patients with poor response to neoadjuva…

2009

Abstract Background Aromatase (CYP19A1) regulates estrogen biosynthesis. Polymorphisms in CYP19A1 have been related to the pathogenesis of breast cancer (BC). Inhibition of aromatase with letrozole constitutes the best option for treating estrogen-dependent BC in postmenopausal women. We evaluate a series of polymorphisms of CYP19A1 and their effect on response to neoadjuvant letrozole in early BC. Methods We analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by radiology at 4th month by World Health Organization (WHO) criteria. Three polymorphisms of CYP19A1, one in exon 7 (rs700519) and two in…

EndoPredict improves the prognostic classification derived from common clinical guidelines in ER-positive, HER2-negative early breast cancer

2012

Background In early estrogen receptor (ER)-positive/HER2-negative breast cancer, the decision to administer chemotherapy is largely based on prognostic criteria. The combined molecular/clinical EndoPredict test (EPclin) has been validated to accurately assess prognosis in this population. In this study, the clinical relevance of EPclin in relation to well-established clinical guidelines is assessed. Patients and methods We assigned risk groups to 1702 ER-positive/HER2-negative postmenopausal women from two large phase III trials treated only with endocrine therapy. Prognosis was assigned according to National Comprehensive Cancer Center Network-, German S3-, St Gallen guidelines and the EPc…

Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes

2015

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular deat…

Dual orexin receptor blocker suvorexant attenuates hypercapnic ventilatory augmentation in mice

2022

Suvorexant (Belsomra(R)), a dual orexin receptor antagonist widely used in the treatment of insomnia, inhibits the arousal system in the brain. However, the drug’s ventilatory effects have not been fully explored. This study aims to investigate the expression of orexin receptors in respiratory neurons and the effects of suvorexant on ventilation. Immunohistology of brainstem orexin receptor OX2R expression was performed in adult mice (n = 4) in (1) rostral ventral respiratory group (rVRG) neurons projecting to the phrenic nucleus (PhN) retrogradely labeled by Fluoro-Gold (FG) tracer, (2) neurons immunoreactive for paired like homeobox 2b (Phox2b) in the parafacial respiratory group/retrotra…