Monthly Archives: December 2010

Efficacy and plasma protein binding

The December issue of Nature Reviews|Drug Discovery includes an informative article from scientists at Pfizer titled ‘The effect of plasma protein binding on in vivo efficacy: misconceptions in drug discovery’.  In it they discuss the ways in which plasma protein … Continue reading

Posted in Med Chem Strategy | Tagged , , , | 1 Comment

Discovery of LX2931 (Sphingosine 1-Phosphate Lyase Inhibitor) & Phase IIa Data

Fingolimod (FTY720, Gilenya), an immunosuppresive agent with activity purported to be mediated by binding of it’s phosphorylated derivative to the sphingosine-1-phosphate receptor 1 (S1P1), was approved earlier in the year as the first orally administered disease modifying therapy for the treatment … Continue reading

Posted in Clinical Candidates, Enzyme Inhibitors | Tagged , , , , , , , , , , , , , , , | Leave a comment

Aromatic chloride to nitrile transformation

Introducing a nitrile in the place of less polar substituents is a fairly common approach to reducing lipophilicity in a lead molecule but in this review from the MedChem group at Pfizer the associated benefits of specifically the aromatic chloride to … Continue reading

Posted in Med Chem Strategy, Synthesis | Tagged , , , , , | Leave a comment

Improved PK profile through fluorine and deuterium incorporation

Compound (1) was identified by scientists at Merck as a potent Aurora kinase inhibitor with the potential to be useful in the treatment of various cancers.  In this paper the authors reveal that the basic amine which is key to good … Continue reading

Posted in Kinase Inhibitors, Kinases | Tagged , , , , , , , , , , , | Leave a comment

Discovery of PF-04457845 (FAAH Inhibitor)

In this latest publication from the Pfizer labs, the authors describe their continuing efforts to identify urea-based, irreversible inhibitors of fatty acid amide hydrolase (FAAH).  Inhibition of FAAH and the concomitant elevation of endogenous levels of fatty acid amides has … Continue reading

Posted in Clinical Candidates, Enzyme Inhibitors | Tagged , , , , , , , , , , , | Leave a comment