Rapid assessment of a novel series of selective CB(2) agonists using parallel synthesis protocols: A Lipophilic Efficiency (LipE) analysis

Thomas Ryckmans; Martin P Edwards; Val A Horne; Ana Monica Correia; Dafydd R Owen; Lisa R Thompson; Isabelle Tran; Michelle F Tutt; Tim Young

doi:10.1016/j.bmcl.2009.05.062

Rapid assessment of a novel series of selective CB(2) agonists using parallel synthesis protocols: A Lipophilic Efficiency (LipE) analysis

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4406-9. doi: 10.1016/j.bmcl.2009.05.062. Epub 2009 May 21.

Authors

Thomas Ryckmans¹, Martin P Edwards, Val A Horne, Ana Monica Correia, Dafydd R Owen, Lisa R Thompson, Isabelle Tran, Michelle F Tutt, Tim Young

Affiliation

¹ Pfizer Discovery Chemistry, Ramsgate Road, Sandwich CT139NJ Kent, United Kingdom. [email protected]

PMID: 19500981
DOI: 10.1016/j.bmcl.2009.05.062

Abstract

A series of libraries were designed using the 1-(cyclopropylmethyl)-2-alkyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-5-ium templates 2a-b, and Sulfonamide derivatives 11a-n proved to be potent agonists of the CB(2) receptor. Analysis of the Lipophilic Efficiency (LipE) of potent compounds provided new insight for the design of potent, metabolically stable CB2 agonists.

MeSH terms

Animals
Binding Sites
Chemistry, Pharmaceutical / methods
Combinatorial Chemistry Techniques
Drug Design
Inhibitory Concentration 50
Ligands
Microsomes, Liver / drug effects
Models, Chemical
Molecular Structure
Nitrogen / chemistry
Rats
Receptor, Cannabinoid, CB2 / chemistry*
Structure-Activity Relationship
Sulfonamides / chemistry

Substances

Ligands
Receptor, Cannabinoid, CB2
Sulfonamides
Nitrogen