Tag Archives: Merck

Drug discovery approaches to minimise drug induced liver injury in man


The recent literature has seen a flurry of papers describing the issue of, and potential approaches to minimising the incidence of, drug-induced liver injury (DILI) in the clinic.   It is well recognised that attrition throughout the development pipeline is often … Continue reading

Posted in Med Chem Strategy, Toxicology | Tagged , , , , , , , , , , , , , , , , | 3 Comments

Synthesis: Sulfonylated Pyridines


Sulfonyl pyridines have utility both as constituents of bioactive molecules and as synthetic intermediates.  Typical methods for their preparation have suffered from the use of odiferous thiols, capricious oxidation steps, poor atom economy, and production of significant amounts of hazardous … Continue reading

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Discovery of MK-1220 (Hepatitis C NS3/4A protease inhibitor)


A recent letter in ACS Med.Chem.Lett. details the optimisation of a series of inhibitors of the Hepatitis C virus (HCV) NS3/4A protease, and is interesting in that it provides detailed pharmacokinetic data for a series of macrocyclic lactones, a class of therapeutic … Continue reading

Posted in Clinical Candidates, Enzyme Inhibitors, Med Chem Strategy | Tagged , , , , , , , , , , , , , , , , , , , , , , , , | 1 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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Working with Ion Channels


Two recent publications highlight the challenges inherent in the targeting of voltage-gated and ion-gated ion channels.  It is only in relatively recent times that technological advances (e.g. higher throughput patch-clamping) have opened up many of these targets to drug discovery … Continue reading

Posted in Ion Channel Blockers, Med Chem Strategy | Tagged , , , , , , , , , , , , , | 2 Comments

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

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