-
Recent Posts
Top Rated
Most Popular:
- Review: Bioisosteres in Drug Design
- Enhancing solubility by disrupting crystal packing
- Improved PK profile through fluorine and deuterium incorporation
- Working with Ion Channels
- TAK-733 & CH4987655 (Allosteric MEK Inhibitors)
- Reducing bioactivation potential by chemical design
- The Discovery of RG1678 (Gly-T1 inhibitor)
- Efficacy and plasma protein binding
- Review: Gamma-secretase modulators
Blogroll
Conferences
Intellectual Property
Journals
MedChem Resources
News
Organic Chemistry Resources
- Abbott adverse events allosteric allosteric inhibitor amine basicity Analgesic animal PK anti-viral AstraZeneca Aurora beta-secretase bioactivation BIRB-796 Boehringer Ingelheim cancer cardiotoxicity cellular potency CGRP chloro CNS penetration computational method crystal packing CYP450 Deuterium Doramapimod FAAH Fatty acid amide hydrolase fluorine free drug functional antagonist Gly-T1 gpcr hepatotoxicity hERG immunosuppressant isostere kinase kinetic isotope effect Lexicon Pharmaceuticals LipE Merck metabolism mTOR nitrile Novartis osteoarthritis P-gp p38 Pain PF-04457845 PF-3845 Pfizer Phase I Phase II Phase III POC PPB protein binding PSA reactive metabolite review RG1678 rheumatoid arthritis Roche S1P1 S1PL Schizophrenia solubility Structural alert Structure Based Design switch pocket synthesis toxicity Transporters X-ray data
Categories
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
