The incorporation of amide groups into biologically active molecules has been proven to be an efficient strategy for drug design and discovery. In this study, we present a simple and practical method for the synthesis of amide-containing quinazolin-4(3)-ones under transition-metal-free conditions. This is achieved through a carbamoyl-radical-triggered cascade cyclization of N3-alkenyl-tethered quinazolinones. Notably, the carbamoyl radical is generated in situ from the oxidative decarboxylative process of oxamic acids in the presence of (NH)SO.
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http://dx.doi.org/10.3390/molecules29050997 | DOI Listing |
J Org Chem
December 2024
Inner Mongolia Key Laboratory of Synthesis and Application of Organic Functional Molecules, Department of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot 010021, China.
A convenient palladium-catalyzed cascade cyclization reaction for the construction of amide-containing indolo[2,1-]isoquinolines from 2-aryl--propenyl indoles with aromatic amines and chloroform is described. A variety of amide-containing indolo[2,1-]isoquinoline compounds have been successfully synthesized in moderate to good yields in which chloroform is employed as the source of CO.
View Article and Find Full Text PDFJ Chem Inf Model
October 2024
Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, BMC, Box 596, SE-751 24, Uppsala, Sweden.
Poly(ADP-ribose) polymerase 1 (PARP1) inhibitors have revolutionized the treatment of many cancers with DNA-repairing deficiencies via synthetic lethality. Advocated by the polypharmacology concept, recent evidence discovered that a significantly synergistic effect in increasing the death of cancer cells was observed by simultaneously perturbating the enzymatic activities of bromodomain-containing protein 4 (BRD4) and PARP1. Here, we developed a novel cheminformatics approach combined with a structure-based method aiming to facilitate the design of dual PARP1-BRD4 inhibitors.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
October 2024
Shanghai Key Laboratory of Green Chemistry and Chemical Processes, State Key Laboratory of Petroleum Molecular & Process Engineering, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China.
A Pd-catalyzed asymmetric isomerization-hydroamidocarbonylation of amide-containing alkenes was developed, affording a variety of chiral α-alkyl succinimides in moderate to good yields with high enantioselectivities. The key to success was introducing bulky 1-adamentyl P-substitution and 2,3,5,6-tetramethoxyphenyl group into the rigid P-chirogenic bisphosphine ligand to create stronger steric hinderance and deeper catalytic pocket. By this approach, regio- or stereo-convergent synthesis of enantiomeric succinimides from the mixture of olefin isomers was achieved.
View Article and Find Full Text PDFChemistry
September 2024
Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, 721302, India.
This paper presents the synthesis and characterization of a series of novel monomeric aqua-ligated iron(III) complexes, [Fe(L)(OH)] (R=OMe, H, Cl, NO), supported by an amide-containing pentadentate N donor ligand, L [HL=2-(((1-methyl-1H-imidazol-2-yl)methyl)(pyridin-2-yl-methyl)amino)-N-(5-R-quinolin-8-yl)acetamide]. The complexes were characterized by various spectroscopic and analytical techniques, including electrochemistry and magnetic measurements. The Fe(III)-hydroxo complexes, [Fe(L)(OH)], were generated in situ by deprotonating the corresponding aqua complexes in a pH ~7 aqueous medium.
View Article and Find Full Text PDFChemMedChem
September 2024
Department of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.
Protein arginine methyltransferase (PRMT) 4 (also known as coactivator-associated arginine methyltransferase 1; CARM1) is involved in a variety of biological processes and is considered as an emerging target class in oncology and other diseases. A successful strategy to identify PRMT substrate-competitive inhibitors has been to exploit chemical scaffolds able to mimic the arginine substrate. (S)-Alanine amide moiety is a valuable arginine mimic for the development of potent and selective PRMT4 inhibitors; however, its high hydrophilicity led to derivatives with poor cellular outcomes.
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