Monthly Archives: February 2011

Reducing bioactivation potential by chemical design


Continuing the theme of an earlier post, an excellent article in Current Topics in Medicinal Chemistry looks at the issue of adverse drug events associated with the formation of reactive intermediates.  The authors (from Novartis) give some background to drug-related … Continue reading

Posted in Med Chem Strategy, Reviews, Software, Toxicology | Tagged , , , , , , , , , , , | 1 Comment

Structure-based design of BACE inhibitors


In a recent post the difficulties of developing drug-like and CNS penetrant inhibitors of β-secretase (BACE-1 or ASP-2) were hinted at (a detailed account of the state of the art can be found in this book).  Many of the reported inhibitors … Continue reading

Posted in Computational Methods, Enzyme Inhibitors, Med Chem Strategy | Tagged , , , , , , , , , , , , , , | 1 Comment

Synthesis: Copper-mediated trifluoromethylation


The introduction of fluorine in the course of a lead optimisation programme has become a key tool in the medicinal chemist’s armoury and many drug candidates incorporate one or more fluorine atoms.  Two reviews published in 2008 in J.Med.Chem. and … Continue reading

Posted in Med Chem Strategy, Synthesis | Tagged , , , , | 2 Comments

Review: Chemical carcinogenicity and mutagenicity


A new review, titled ‘Mechanisms of chemical carcinogenicity and mutagenicity: a review with implications for predictive toxicology’ , collates the experimentally derived mechanistic knowledge relating to this type of chemically induced toxicity.  Whilst a lot of the material is well … Continue reading

Posted in Toxicology | Tagged , , , , , , | 1 Comment

Site Update: New Links


A link to the UK-QSAR and Chemoinformatics Group has been added to the MedChem Resources links.  This site maintains a repository of slide presentations from the group’s meetings over the last decade.  The slide packs are a little mixed in … Continue reading

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TAK-733 & CH4987655 (Allosteric MEK Inhibitors)


The mitogen-activated protein kinase (MAPK) signalling cascade is one of the key pathways regulating cell proliferation and differentiation and aberrant activation of this pathway is implicated in a number of cancers. Targeting components of the cascade thus has the potential … Continue reading

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

Discovery of MK-2918 (CGRP Antagonist)


The triptan drugs have been highly successful in the treatment of migraine, but adverse effects and low responder rates in some patients have provided the impetus to develop alternative therapies.   Blockers of the calcitonin gene-related peptide (CGRP) receptor have … Continue reading

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