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Design and synthesis of potent and orally active GPR4 antagonists with modulatory effects on nociception, inflammation, and angiogenesis.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2017 Aug 15; Vol. 25 (16), pp. 4512-4525. Date of Electronic Publication: 2017 Jun 29. - Publication Year :
- 2017
-
Abstract
- GPR4, a G-protein coupled receptor, functions as a proton sensor being activated by extracellular acidic pH and has been implicated in playing a key role in acidosis associated with a variety of inflammatory conditions. An orally active GPR4 antagonist 39c was developed, starting from a high throughput screening hit 1. The compound shows potent cellular activity and is efficacious in animal models of angiogenesis, inflammation and pain.<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Subjects :
- Administration, Oral
Animals
Anti-Inflammatory Agents, Non-Steroidal administration & dosage
Anti-Inflammatory Agents, Non-Steroidal chemistry
Arthritis drug therapy
Arthritis metabolism
COS Cells
Chlorocebus aethiops
Dose-Response Relationship, Drug
Female
HEK293 Cells
HeLa Cells
Humans
Inflammation metabolism
Mice
Molecular Structure
Pain drug therapy
Pain metabolism
Rats
Rats, Sprague-Dawley
Receptors, G-Protein-Coupled metabolism
Structure-Activity Relationship
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Drug Design
Inflammation drug therapy
Receptors, G-Protein-Coupled antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 25
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 28689977
- Full Text :
- https://doi.org/10.1016/j.bmc.2017.06.050