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ANRORC type rearrangement/intermolecular cyclocondensation cascade of 5,6-dicyano-3-(2-oxo-2-ethyl)pyrazin-2(1)-ones with hydrazine hydrate for the synthesis of 2-(pyrazol-3-yl)imidazo[4,5-]pyridazines.
Org Biomol Chem
January 2025
Mulliken Center for Theoretical Chemistry University of Bonn Beringstr. 4, 53115 Bonn, Germany.
A novel HSO-catalyzed ANRORC-type rearrangement of pyrazinones to imidazoles proceeding through pyridazino[]annulation with simultaneous introduction of a pyrazole ring at position 2 of the imidazole system has been developed, which offers efficient and expedited access to new biheterocyclic systems - 2-(pyrazol-3-ul)imidazoles and 2-(pyrazol-3-yl)imidazo[4,5-]pyridazines. Diverse bi--heterocyclic systems with the imidazo[4,5-]pyridazine-4,7-diamine moiety could be obtained in excellent yield when 5,6-dicyano-3-(2-oxo-2-ethyl)pyrazin-2(1)-ones interact with hydrazines the selective spiro-formation in a tandem ring-opening/ring-closing process, which allowed the simultaneous construction of five new C-N bonds. This new method is compatible with an array of functional groups, proceeds under mild reaction conditions with the involvement of commercially available reagents.
View Article and Find Full Text PDF[F]BCPP-EF positron emission tomography of rat ovaries for evaluation of mitochondrial function.
Nucl Med Biol
January 2025
Central Research Laboratory, Hamamatsu Photonics K.K., Hamana, Hamamatsu, Shizuoka 434-8601, Japan.
Background: The ovary is an important female organ not only for pregnancy but also for the regulation of life activities via hormone release. Ovarian function is measured by blood hormone levels, but the hormone level reflects only the ovarian reserve and no other essential ovarian functions, such as nurturing and expelling follicles. Ovarian fibrosis is related to essential ovarian function; however, the existing methods for evaluating fibrosis are invasive.
View Article and Find Full Text PDFFlurpiridaz F 18: First Approval.
Am J Cardiovasc Drugs
January 2025
Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.
Flurpiridaz F 18 (FLYRCADO™) is an intravenous (IV) radioactive diagnostic drug being developed by GE Healthcare and Lantheus Medical Imaging for use in positron emission tomography (PET) myocardial perfusion imaging (MPI) to detect coronary artery disease (CAD). In September 2024, flurpiridaz F 18 was approved in the USA for PET MPI under rest or stress (pharmacologic or exercise) in adult patients with known or suspected CAD to evaluate for myocardial ischemia and infarction. This article summarizes the milestones in the development of flurpiridaz F 18 leading to this first approval for use in PET MPI in adult patients to evaluate for myocardial ischemia and infarction.
View Article and Find Full Text PDFReal-World Impact of Olaparib Exposure in Advanced Pancreatic Cancer Patients Harboring Germline BRCA1-2 Pathogenic Variants.
Cancer Med
February 2025
Department of Medical Oncology, IRCCS Ospedale San Raffaele, Milan, Italy.
Introduction: Pancreatic cancer arising in the context of BRCA predisposition may benefit from poly(ADP-ribose) polymerase inhibitors. We analyzed real-world data on the impact of olaparib on survival in metastatic pancreatic cancer patients harboring germline BRCA mutations in Italy, where olaparib is not reimbursed for this indication.
Methods: Clinico/pathological data of pancreatic cancer patients with documented BRCA1-2 germline pathogenic variants who had received first-line chemotherapy for metastatic disease were collected from 23 Italian oncology departments and the impact of olaparib exposure on overall survival (OS) was analyzed.
Comparative Analyses of Antiviral Potencies of Second-Generation Integrase Strand Transfer Inhibitors (INSTIs) and the Developmental Compound 4d Against a Panel of Integrase Quadruple Mutants.
Viruses
January 2025
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
Second-generation integrase strand transfer inhibitors (INSTIs) are strongly recommended for people living with HIV-1 (PLWH). The emergence of resistance to second-generation INSTIs has been infrequent and has not yet been a major issue in high-income countries. However, the delayed rollouts of these INSTIs in low- to middle-income countries during the COVID-19 pandemic combined with increased transmission of drug-resistant mutants worldwide are leading to an increase in INSTI resistance.
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