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Low brain penetrant CB1 receptor agonists for the treatment of neuropathic pain.

Abstract：

: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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Adam JM,Clark JK,Davies K,Everett K,Fields R,Francis S,Jeremiah F,Kiyoi T,Maidment M,Morrison A,Ratcliffe P,Prosser A,Schulz J,Wishart G,Baker J,Boyce S,Campbell R,Cottney JE,Deehan M,Martin I

doi

10.1016/j.bmcl.2012.02.048

subject

Has Abstract

pub_date

2012-04-15 00:00:00

pages

2932-7

issue

8

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(12)00240-5

journal_volume

22

pub_type

杂志文章

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