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- Review: Bioisosteres in Drug Design
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- Enhancing solubility by disrupting crystal packing
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Monthly Archives: March 2011
Review: Bioisosteres in Drug Design
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
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
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 animal PK, anti-viral, BILN-2061, Boceprevir, Boehringer Ingelheim, cardiotoxicity, Ensemble Therapeutics Corp., HCV, Hepatitis C, macrocyclic lactone, Merck, MK-1220, MK-7009, NS3/4A, PEG-intron, pegasys, protease, ribavirin, rule of five, SCH 503034, Schering-Plough, Telaprevir, Vaniprevir, Vertex, VX-950
1 Comment
Enhancing solubility by disrupting crystal packing
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
Posted in Med Chem Strategy, Reviews
Tagged BCS, crystal packing, dihedral angle, FDA, formulation, logP, permeability, solubility, University of Tokyo
6 Comments
Optimization of plasma protein binding (again…)
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
Posted in Med Chem Strategy, Uncategorized
Tagged CNS penetration, Depomed, free drug, Genentech, P-gp, PPB, protein binding, shift assay
1 Comment
