Some new N-substituted 6,7-benzomorphans were prepared and tested for analgetic activity. The compounds (I) and (II), which proved the most active in a preliminary screening, were submitted to a more detailed investigation, and their ED50 was determined in mice by the phenylquinone, hot-plate and tail-pinch tests. Studies of acute toxicity and physical dependence capacity were also performed.
Download full-text PDF |
Source |
---|
J Org Chem
January 2025
Pharmacy College, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji'nan 250117, China.
Herein, we report a Cu-DTBP-catalyzed [3 + 2] cycloaddition reaction between 1-(2-oxo-2-phenylethyl)--indole-3-aldehyde and arylalkene, using DMF as the solvent. Under relatively mild reaction conditions, a series of indole compounds were synthesized in moderate yields (up to 73%). This protocol features good functional group tolerance and high atom economy.
View Article and Find Full Text PDFBioorg Chem
January 2025
Laboratory of Organic and Medicinal Chemistry, Department of Chemistry, Central University of Punjab, Bathinda, India, 151401. Electronic address:
The pathology of Alzheimer's disease (AD) is complex due to its multifactorial nature and single targeting drugs proved inefficient. A series of novel 4-N-substituted-2-phenylquinazoline derivatives was designed and synthesized as potential multi-target directed ligands (MTDLs) through dual inhibition of AChE and MAO-B enzymes along with Aβ aggregation inhibition for the treatment of AD. Two compounds in the series, VAV-8 and VAV-19 were found to be the most potent inhibitors of both AChE and MAO-B enzymes and moderate inhibitor of Aβ, with good thermodynamic stability at the binding pocket of the enzymes.
View Article and Find Full Text PDFMolecules
December 2024
School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
It is established that reverse hydroxamate analogs of fosmidomycin inhibit the growth of by inhibiting 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), the second enzyme of the non-mevalonate pathway, which is absent in humans. Recent biochemical studies have demonstrated that novel reverse fosmidomycin analogs with phenylalkyl substituents at the hydroxamate nitrogen exhibit inhibitory activities against DXR at the nanomolar level. Moreover, crystallographic analyses have revealed that the phenyl moiety of the -phenylpropyl substituent is accommodated in a previously unidentified subpocket within the active site of DXR.
View Article and Find Full Text PDFMolecules
December 2024
Institut für Pharmazeutische und Medizinische Chemie, Universität Münster, Corrensstraße 48, D-48149 Münster, Germany.
The serine/threonine kinase CK2 (formerly known as casein kinase II) plays a crucial role in various CNS disorders and is highly expressed in various types of cancer. Therefore, inhibiting this key kinase could be promising for the treatment of these diseases. The CK2 holoenzyme is formed by the recruitment of two catalytically active CK2α and/or CK2α' subunits by a regulatory CK2β dimer.
View Article and Find Full Text PDFChem Commun (Camb)
January 2025
Institute of Medicine and Materials Applied Technologies, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, Shandong 273165, China.
A mild and efficient [3+2] annulation of phenidones with propiolates has been developed to access -substituted indole alkylamides, enabled by merging electrochemistry with iridium catalysis using an undivided cell at room temperature. The mechanistic studies have confirmed that the electrochemically mediated catalytic cycle of Ir-Ir-Ir exhibits enhanced efficiency, mild reaction conditions, and unconventional selectivity.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!