A ligand-free, palladium-catalyzed aminoarylation reaction of the unactivated alkenes in β,γ-unsaturated hydrazones is described. This protocol enables efficient and simultaneous formation of C(sp)-N and C(sp)-C(sp) bonds under mild conditions, providing a practical and general approach to various diversely substituted dihydropyrazoles in generally good yields, without the use of any stoichiometric external oxidant.
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http://dx.doi.org/10.1021/acs.orglett.7b02480 | DOI Listing |
J Org Chem
November 2024
Pharmacy College, Institute of Pharmacology, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271016, China.
A route for nitrification and C-H activation/cyclization of ()--allyl-'-benzylidenebenzenesulfonohydrazide and cobalt nitrate via an iron(II)-catalyzed cascade reaction to synthesize nitrated dihydropyrazoles has been developed. The method features convenient operation and good functional group tolerance. In addition, it employs insensitive and inexpensive FeSO as the catalyst and provides a direct approach for the preparation of dihydropyrazoles.
View Article and Find Full Text PDFJ Med Chem
September 2024
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.
Receptor-interacting serine/threonine protein kinase 1 (RIPK1) has emerged as an important regulator of pathologic cell death and inflammation and is implicated in the pathologies of various central nervous system diseases. In this study, we reported the development of three potent dihydropyrazole-cored RIPK1 positron emission tomography (PET) ligands [F]-. Among these, [F] showed specific binding to RIPK1 in mouse brain sections through autoradiography and exhibited favorable brain kinetics in mice, characterized by a high initial uptake (brain = 4.
View Article and Find Full Text PDFEur J Med Chem
December 2024
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, PR China; Center for Advanced Materials Research & Faculty of Arts and Sciences, Beijing Normal University, Zhuhai, 519087, PR China.
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) regulates programmed cell death and inflammation, contributing to a wide range of human pathologies, including inflammatory disorders, neurodegenerative conditions, and cancer. Despite this, no RIPK1 positron emission tomography (PET) ligand with significant in vivo specificity has been reported to date. In this work, we designed and synthesized a new family of dihydropyrazole-cored ligands suitable for F-labeling at the late stage.
View Article and Find Full Text PDFChem Commun (Camb)
September 2024
School of Petrochemical Engineering, Changzhou University, Changzhou 213164, P. R. China.
A photocatalytic trifluoromethylation/cyclization reaction of -allyl and -homoallyl aldehyde hydrazones with trifluoromethyl thianthrenium triflate was developed for the synthesis of trifluoromethylated dihydropyrazoles and tetrahydropyridazines. Besides, PhI(OCCHF) was employed to realize the construction of difluoromethylated dihydropyrazoles and tetrahydropyridazines. These protocols exhibit a broad substrate scope and good functional group tolerance.
View Article and Find Full Text PDFChem Biol Drug Des
July 2024
School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, China.
Previous studies have indicated that heterocyclic substituted dihydropyrazole derivatives, particularly MW-19, potentially exert anticancer activity in vitro; however, the underlying mechanism remains unknown. The present study was designed to investigate the mechanisms underlying MW-19 activity in triple-negative breast cancer cells. A sulforhodamine B assay was performed to evaluate cell proliferation inhibition rates, and the antitumor effect of MW-19 was evaluated in mice with HCC-1806 xenografts.
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