Novel 2-imidazoles have been identified as potent partial agonists of the alpha(1A) adrenergic receptor, with good selectivity over the alpha(1B), alpha(1D) and alpha(2A) receptor sub-types. Sulfonamide 23 possessed attractive drug-like properties with respect to physicochemical and ADME properties and wide ligand selectivity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2008.03.070 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Benzofuranyl-2-imidazoles as imidazoline I receptor ligands for Alzheimer's disease.
Eur J Med Chem
October 2021
Laboratory of Medicinal Chemistry (Associated Unit to CSIC), Department of Pharmacology, Toxicology and Medicinal Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Biomedicine (IBUB), University of Barcelona, Av. Joan XXIII, 27-31, E-08028, Barcelona, Spain. Electronic address:
Recent findings unveil the pharmacological modulation of imidazoline I receptors (I-IR) as a novel strategy to face unmet medical neurodegenerative diseases. In this work, we report the chemical characterization, three-dimensional quantitative structure-activity relationship (3D-QSAR) and ADMET in silico of a family of benzofuranyl-2-imidazoles that exhibit affinity against human brain I-IR and most of them have been predicted to be brain permeable. Acute treatment in mice with 2-(2-benzofuranyl)-2-imidazole, known as LSL60101 (garsevil), showed non-warning properties in the ADMET studies and an optimal pharmacokinetic profile.
View Article and Find Full Text PDFAldehyde dehydrogenase variation enhances effect of pesticides associated with Parkinson disease.
Neurology
February 2014
From the Department of Neurology (A.G.F., B.R., J.M.B.), David Geffen School of Medicine at UCLA, Los Angeles; Department of Molecular Toxicology (A.G.F., B.R., J.M.B.), University of California, Los Angeles; Departments of Epidemiology (S.L.R., B.R.) and Environmental Health Sciences (B.R.), UCLA Fielding School of Public Health, Los Angeles; Department of Preventive Medicine (M.C.), Keck School of Medicine of USC, Los Angeles; and Parkinson's Disease Research, Education, and Clinical Center (J.M.B.), Greater Los Angeles Veterans Affairs Medical Center, Los Angeles, CA.
Objective: The objective of this study was to determine whether environmental and genetic alterations of neuronal aldehyde dehydrogenase (ALDH) enzymes were associated with increased Parkinson disease (PD) risk in an epidemiologic study.
Methods: A novel ex vivo assay was developed to identify pesticides that can inhibit neuronal ALDH activity. These were investigated for PD associations in a population-based case-control study, the Parkinson's Environment & Genes (PEG) Study.
Novel 2-imidazoles as potent, selective and CNS penetrant alpha1A adrenoceptor partial agonists.
Bioorg Med Chem Lett
December 2008
Department of Chemistry, Pfizer Global Research and Development, Sandwich Labs, IPC432, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK.
A novel series of central nervous system (CNS) penetrant indane 2-imidazoles have been identified as potent, partial agonists of the alpha(1A) adrenergic receptor, having good selectivity over the alpha(1B), alpha(1D) and alpha(2) sub-types. A key structural motif to impart selectivity is a methylene spacer between the indane and a pendant substituent, which includes heterocycles, sulphones and ethers. Introduction of an ortho-halogen to this group led to a lowering of intrinsic efficacy (E(max)).
View Article and Find Full Text PDFNovel 2-imidazoles as potent and selective alpha1A adrenoceptor partial agonists.
Bioorg Med Chem Lett
May 2008
Department of Chemistry, Pfizer Global Research and Development, Sandwich Labs, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK.
Novel 2-imidazoles have been identified as potent partial agonists of the alpha(1A) adrenergic receptor, with good selectivity over the alpha(1B), alpha(1D) and alpha(2A) receptor sub-types. Sulfonamide 23 possessed attractive drug-like properties with respect to physicochemical and ADME properties and wide ligand selectivity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!