Monthly Archives: March 2011

Review: Optimizing CNS access

Posted on March 30, 2011 by

Neurotherapeutic agents generally illicit their effects by acting on receptors in the central nervous system (CNS) and a short review in Expert Opin. Drug Discov. highlights the current best practices and recent developments in targeting molecules to the brain.  The … Continue reading →

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Review: Bioisosteres in Drug Design

Posted on March 21, 2011 by

An excellent J.Med.Chem. perspective titled ‘Synopsis of Some Recent Tactical Applications of Bioisosteres in Drug Design‘ has just published (The article is based on a short course presented at an ACS Prospectives conference in 2009).  The author gives a brief … Continue reading →

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Discovery of PF-04691502 (PI3K/mTOR dual inhibitor)

Posted on March 17, 2011 by

Rapamycin and it’s analogues (or rapalogues e.g. CCI-779) modulate the phosphatidylinositol 3-kinase (PI3K) signalling cascade by binding to an allosteric site on the mTORC1 complex (Mammalian target of rapamycin (mTOR), a class IV PI3K protein kinase, forms two functional complexes, … Continue reading →

Posted in Clinical Candidates, Enzyme Inhibitors, Kinase Inhibitors, Kinases, Med Chem Strategy | Tagged , , , , , , , , , , , , , , , , , , , , , , , | 1 Comment

Synthesis: Sulfonylated Pyridines

Posted on March 15, 2011 by

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)

Posted on March 10, 2011 by

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

Enhancing solubility by disrupting crystal packing

Posted on March 7, 2011 by

Drug candidates can be classified, according to the BCS system, into four groups on the basis of their permeability and aqueous solubility.  Molecules with lower solubility tend to be more difficult to develop and are subject to closer scrutiny by … Continue reading →

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Optimization of plasma protein binding (again…)

Posted on March 2, 2011 by

Following hot on the heels of the Pfizer paper we blogged recently, comes a very similar publication from scientists at Genentech/Depomed.  Titled ‘Do We Need to Optimize Plasma Protein and Tissue Binding in Drug Discovery?’, the authors highlight the apparent … Continue reading →

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