An efficient Pd-catalyzed cascade alkynylation of aryl phenol-tethered alkynes with alkynyl bromides is described. This protocol could provide various conjugated 1,3-enynes possessing a polysubstituted spirocyclohexadienone, as well as an all-carbon tetrasubstituted alkene moiety. The products could also undergo ring-expansion and cyclization transformations under different conditions to convert to diverse fused cyclic scaffolds.
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http://dx.doi.org/10.1021/acs.orglett.3c02336 | DOI Listing |
Curr Treat Options Oncol
January 2025
Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin, 300052, Heping District, China.
According to the guidelines, the primary treatment for multiple myeloma is still based on drugs such as carfilzomib, lenalidomide, or daratumumab. However, patients with relapsed/refractory multiple myeloma (RRMM) may be insensitive or develop resistance to the above therapeutic medications. Thus, formulating standardized and rational treatment regimens for such patients remains an area for consideration.
View Article and Find Full Text PDFJ Mater Chem B
January 2025
Institute of Inorganic Chemistry, Leibniz University Hannover, Callinstraße 3-9, 30167 Hannover, Germany.
The increasing prevalence of antimicrobial resistance and adverse effects of systemic treatments calls for urgent reevaluation of current methods that rely on excessive, uncontrolled drug administration. In recent years triggerable systems have emerged as promising alternatives, enabling time-controlled and localized drug release, which are only activated if necessary. Light is an obvious candidate as an external trigger, since it allows for localized activation, is non-invasive and its wavelength and intensity can be tailored to fit the demands of the drug release system.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Institute of Chemistry Chinese Academy of Sciences, Key Laboratory of Organic Solids, Zhongguancun North First Street 2, 100190, 100190, Beijing, CHINA.
The regulation of oxidative stress in living cells is essential for maintaining cellular processes and signal transduction. However, developing straightforward strategies to activate oxidative stress-sensitive membrane channels in situ poses significant challenges. In this study, we presented a chemiluminescence resonance energy transfer (CRET) system based on a conjugated oligomer, oligo(p-phenylenevinylene)-imidazole (OPV-Im), designed for the activation of transient receptor potential melastatin 2 (TRPM2) calcium channels in situ by superoxide anion (O2•-) without requiring external light sources.
View Article and Find Full Text PDFAdv Mater
January 2025
Department of Chemistry, The Chinese University of Hong Kong, Shatin, N. T., Hong Kong, 999077, China.
The globally prevalent rotator cuff tear has a high re-rupture rate, attributing to the failure to reproduce the interfacial fibrocartilaginous enthesis. Herein, a hierarchically organized membrane is developed that mimics the heterogeneous anatomy and properties of the natural enthesis and finely facilitates the reconstruction of tendon-bone interface. A biphasic membrane consisting of a microporous layer and a mineralized fibrous layer is constructed through the non-solvent induced phase separation (NIPS) strategy followed by a co-axial electrospinning procedure.
View Article and Find Full Text PDFPharmacol Res Perspect
February 2025
Clinical Pharmacology, Oncology, Pfizer Inc., Boulder, Colorado, USA.
Binimetinib is a MEK1/2 inhibitor particularly active in cells harboring activating mutations in the MAP kinase pathway, especially in BRAF and NRAS. Binimetinib, in combination with encorafenib, has received marketing approval in several jurisdictions for the treatment of patients with BRAF V600E or V600K mutant melanoma. The absorption, distribution, metabolism, and excretion of binimetinib were evaluated by administering a carbon 14-labeled binimetinib 45 mg dose (containing 40 μCi of radiolabeled material) to 6 healthy male participants.
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