Isosteric replacement of the urea group of lead compound 1 led to novel substituted piperidine phenylamide analogues. SAR on the electron-induced effects of various linkers as well as substituents on the phenyl rings and the piperidine nitrogen has been investigated. Many single-digit nanomolar MCH R1 antagonists have been identified from this series.
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http://dx.doi.org/10.1016/j.bmcl.2006.04.061 | DOI Listing |
Biomater Adv
December 2024
Department of Biomedical Engineering, Whiting School of Engineering, The Johns Hopkins University, Baltimore, MD, USA; Translational Tissue Engineering Center, Whiting School of Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address:
This study defines biochemical mechanisms that contribute to novel neural-regenerative activities we recently demonstrated for thiol-modified ManNAc analogs in human neural stem cells (hNSCs) by comparing our lead drug candidate for brain repair, "TProp," to a "size-matched" N-alkyl control analog, "But." These analogs biosynthetically install non-natural sialic acids into cell surface glycans, altering cell surface receptor activity and adhesive properties of cells. In this study, TProp modulated sialic acid-related biology in hNSCs to promote neuronal differentiation through modulation of cell adhesion molecules (integrins α6, β1, E-cadherin, and PSGL-1) and stem cell markers.
View Article and Find Full Text PDFCurr Top Med Chem
January 2025
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka, India.
Background: Several chemical studies described the physiological efficacy of 1,4- dihydropyridines (DHPs). DHPs bind to specific sites on the α1 subunit of L-type calcium channels, where they demonstrate a more pronounced inhibition of Ca2+ influx in vascular smooth muscle compared to myocardial tissue. This selective inhibition is the basis for their preferential vasodilatory action on peripheral and coronary arteries, a characteristic that underlies their therapeutic utility in managing hypertension and angina.
View Article and Find Full Text PDFCurr Cancer Drug Targets
January 2025
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India.
Cancer manifests as uncontrolled cell proliferation. Tankyrase, a poly(ADP-ribose) polymerase member, is vital in Wnt signal transmission, making it a promising cancer therapy target. The Wnt/β-catenin pathway regulates critical biological processes like genomic stability, gene expression, energy utilization, and apoptosis.
View Article and Find Full Text PDFSAR QSAR Environ Res
November 2024
Research and Development Center, Bioinnov Solutions LLP, Salem, India.
Hepatocellular carcinoma (HCC) ranks fourth in cancer-related mortality worldwide. This study aims to uncover the genes and pathways involved in HCC through network pharmacology (NP) and to discover potential drugs via machine learning (ML)-based ligand screening. Additionally, toxicity prediction, molecular docking, and molecular dynamics (MD) simulations were conducted.
View Article and Find Full Text PDFJ Enzyme Inhib Med Chem
December 2025
Laboratory of Biochemistry and Molecular Biology, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy.
Antibiotic resistance stands as the foremost post-pandemic threat to public health. The urgent need for new, effective antibacterial treatments is evident. Protein-protein interactions (PPIs), owing to their pivotal role in microbial physiology, emerge as novel and attractive targets.
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