Pyrazole ligands: structure-affinity/activity relationships and estrogen receptor-alpha-selective agonists.
- S. Stauffer, C. Coletta, J. Katzenellenbogen
- Biology, ChemistryJournal of Medicinal Chemistry
- 28 November 2000
Investigations suggest that the pyrazole triols prefer to bind to ERalpha with their C(3)-phenol in the estradiol A-ring binding pocket and that binding selectivity results from differences in the interaction of thePyrazole core and C(4)-propyl group with portions of the receptor where ERalpha has a smaller residue than ERbeta.
Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: Identification of ML300 and…
Discovery, synthesis, and structure-based optimization of a series of N-(tert-butyl)-2-(N-arylamido)-2-(pyridin-3-yl) acetamides (ML188) as potent noncovalent small molecule inhibitors of the severe…
- Jon Jacobs, V. Grum-Tokars, S. Stauffer
- Chemistry, BiologyJournal of Medicinal Chemistry
- 24 January 2013
16-(R) is a noncovalent SARS-CoV 3CL Pro inhibitor with moderate MW and good enzyme and antiviral inhibitory activity and provides an excellent starting point for the further design and refinement of 3CLpro inhibitors that act by a non covalent mechanism of action.
Structure-Based Optimization of ML300-Derived, Noncovalent Inhibitors Targeting the Severe Acute Respiratory Syndrome Coronavirus 3CL Protease (SARS-CoV-2 3CLpro)
In vitro DMPK profiling highlights key areas where further optimization in the series is required to obtain useful in vivo probes, and nanomolar activity in these respective assays, comparable in potency to remdesivir, have implications for antiviral development to combat current and future SARS-like zoonotic coronavirus outbreaks.
Reinforced uncrosslinked poly (vinyl alcohol) gels produced by cyclic freezing-thawing processes: a short review
Discovery of Novel Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5 Reveals Chemical and Functional Diversity and In Vivo Activity in Rat Behavioral Models of Anxiolytic and…
Discovery of structurally and functionally diverse allosteric modulators of mGluR5 that demonstrate in vivo efficacy in rodent models of anxiety and antipsychotic activity provide further support for the tremendous diversity of chemical scaffolds and modes of efficacy of mR5 ligands.
Functional Impact of Allosteric Agonist Activity of Selective Positive Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5 in Regulating Central Nervous System Function
It is suggested that the level of receptor expression influences the ability of mGlu5 PAMs to act as allosteric agonists in vitro and that ago-PAM activity observed in cell-based assays may not be important for in vivo efficacy.
Poly (vinyl alcohol) hydrogels prepared by freezing-thawing cyclic processing
Investigating Metabotropic Glutamate Receptor 5 Allosteric Modulator Cooperativity, Affinity, and Agonism: Enriching Structure-Function Studies and Structure-Activity Relationships
An operational model of allosterism that allows quantitative estimation of modulator affinity and cooperativity values is validated and can be applied to PAM and NAM potency curves in combination with maximal fold-shift data to derive reliable estimates of modulators affinities.