Low brain penetrant CB1 receptor agonists for the treatment of neuropathic pain
| Autor: | Maurice Maidment, Angus John Morrison, Keneth Davies, Fiona Jeremiah, Grant Wishart, Alan Prosser, Robert A. Campbell, James Baker, Stuart Francis, Julia M. Adam, Ruth Fields, Susan Boyce, John K. Clark, Maureen Deehan, Jean E. Cottney, Takao Kiyoi, Iain Martin, Paul Ratcliffe, Kathryn Everett, Jurgen Schulz |
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| Rok vydání: | 2012 |
| Předmět: |
Agonist
Indoles Cannabinoid receptor medicine.drug_class medicine.medical_treatment Clinical Biochemistry Pharmaceutical Science Pharmacology Biochemistry Polar surface area Mice Receptor Cannabinoid CB1 Drug Discovery medicine Animals Humans Receptor Molecular Biology Oxadiazoles Chemistry Organic Chemistry Brain Penetration (firestop) medicine.disease Rats Drug Design Neuropathic pain Neuralgia Molecular Medicine Cannabinoid Caco-2 Cells |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 22:2932-2937 |
| ISSN: | 0960-894X |
| Popis: | Novel, low brain penetrant, orally bioavailable CB1 receptor agonists were designed starting from a mature lead series of potent brain penetrant CB1 receptor agonists. Increasing the calculated polar surface area was found to be a good strategy for reducing brain penetration whilst retaining drug-like properties. This in silico approach led to the discovery of LBP1, an orally bioavailable, low brain penetrant CB1 receptor agonist with robust activity in rodent models of neuropathic pain and a good preclinical therapeutic profile, which was selected for clinical development. |
| Databáze: | OpenAIRE |
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