Low brain penetrant CB1 receptor agonists for the treatment of neuropathic pain
2012; Elsevier BV; Volume: 22; Issue: 8 Linguagem: Inglês
10.1016/j.bmcl.2012.02.048
ISSN1464-3405
AutoresJulia M. Adam, John K. Clark, Keneth Davies, Kathryn Everett, Ruth Fields, Stuart Francis, Fiona Jeremiah, Takao Kiyoi, Maurice S. Maidment, Angus J. Morrison, Paul Ratcliffe, Alan Prosser, Jürgen Schulz, Grant Wishart, James Α. Baker, Susan Boyce, Robert A. Campbell, Jean E. Cottney, Maureen R. Deehan, Iain Martin,
Tópico(s)Neuroscience and Neuropharmacology Research
ResumoNovel, 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.
Referência(s)