A5063012941- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Immune Cell Function and Interaction
- Chemical Synthesis and Analysis
- Phenothiazines and Benzothiazines Synthesis and Activities
- PI3K/AKT/mTOR signaling in cancer
- CAR-T cell therapy research
- Asthma and respiratory diseases
- Sleep and related disorders
- Estrogen and related hormone effects
- Protein Kinase Regulation and GTPase Signaling
- Monoclonal and Polyclonal Antibodies Research
- Sleep and Wakefulness Research
- Calcium signaling and nucleotide metabolism
- Drug Transport and Resistance Mechanisms
- T-cell and B-cell Immunology
- Growth Hormone and Insulin-like Growth Factors
- Pharmacological Receptor Mechanisms and Effects
- Biomedical Research and Pathophysiology
- Circadian rhythm and melatonin
- Protein Degradation and Inhibitors
- Pancreatic function and diabetes
- Inflammatory mediators and NSAID effects
- Ion Channels and Receptors
- Lung Cancer Research Studies
Janssen (United States)
2015-2023
Lundbeck (United States)
2006-2011
GPR139 is an orphan G-protein-coupled receptor expressed in the central nervous system. To identify its physiologic ligand, we measured activity from recombinant cells after treatment with amino acids, ligands, serum, and tissue extracts. was using guanosine 5'-O-(3-[(35)S]thio)-triphosphate binding, calcium mobilization, extracellular signal-regulated kinases phosphorylation assays. Amino acids L-tryptophan (L-Trp) L-phenylalanine (L-Phe) activated GPR139, EC50 values 30- to 300-μM range,...
Prostaglandin D<sub>2</sub> (PGD<sub>2</sub>) is one of a family biologically active lipids derived from arachidonic acid via the action COX-1 and COX-2. PGD<sub>2</sub> released mast cells binds primarily to two G protein-coupled receptors, namely DP1 DP2, latter also known as chemoattractant receptor-homologous molecule expressed on Th2 cells. DP2 predominantly eosinophils, cells, basophils, but it lesser extent monocytes, epithelial Interaction its metabolites with results in cellular...
A focused high throughput screening for GPR139 was completed a select 100K compounds, and new agonist leads were identified. Subsequent analysis structure-activity relationship studies identified (S)-3-chloro-N-(2-oxo-2-((1-phenylethyl)amino)ethyl)benzamide 7c as potent selective of hGPR139 with an EC50 = 16 nM. The compound found to cross the blood-brain barrier have good drug-like properties amenable oral dosing in rat.
A highly effective one-pot Friedländer quinoline synthesis from o-nitroarylcarbaldehydes and ketones or aldehydes was developed the scope limitations of method were examined. The reduced to o-aminoarylcarbaldehydes with iron in presence a catalytic amount aqueous hydrochloric acid; amino compounds then condensed situ form mono- disubstituted quinolines, respectively, good-to-excellent yields (58-100%).
NKG2D (natural-killer group 2, member D) is a homodimeric transmembrane receptor that plays an important role in NK, γδ+, and CD8+ T cell-mediated immune responses to environmental stressors such as viral or bacterial infections oxidative stress. However, aberrant signaling has also been associated with chronic inflammatory autoimmune diseases, thought be attractive target for intervention. Here, we describe comprehensive small-molecule hit identification strategy two distinct series of...
Herein, we describe a series of substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines as potent GluN2B negative allosteric modulators. Exploration several five- and six-membered heterocycles led to the identification O-linked pyrimidine analogues that possessed balance potency desirable ADME profiles. Due initial observations metabolic saturation, early metabolite studies were conducted on compound 18, results drove further iterative optimization efforts avoid formation undesired...
The orexin system consists of two neuropeptides (orexin-A and orexin-B) that exert their mode action on receptors (orexin-1 orexin-2). While the role orexin-2 receptor is established as an important modulator sleep wake states, orexin-1 believed to play a in addiction, panic, or anxiety. In this manuscript, we describe optimization nonselective substituted azabicyclo[2.2.1]heptane dual antagonist (DORA) into orally bioavailable, brain penetrating, selective (OX1R) antagonists. This resulted...
<b>Abstract ID 128111</b> <b>Poster Board 364</b> Natural killer group 2D (NKG2D) is a homodimeric transmembrane activating immunoreceptor whose function to detect and eliminate infected, stressed, or transformed cells that are targeted due upregulation of NKG2D ligands (NKG2DL). associates with specific adaptor molecule, the DNAX-activating protein 10kDa (DAP10), which contains signaling sequence needed for activation. has also been associated chronic inflammatory autoimmune diseases...
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 200 leading journals. To access Abstract, please click on HTML or PDF.