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Categories
Category Archives: Enzyme Inhibitors
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
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
Halogen Bonding
Investigators at Roche recently published a communication describing a systematic study of halogen bonding effects in protein-ligand complexes of human Cathepsin L (hCatL). They found that an inhibitor incorporating a 4-chlorophenyl moiety enhanced binding affinity by a factor of 13, … Continue reading
Posted in Computational Methods, Enzyme Inhibitors, Med Chem Strategy
Tagged Cathepsin L, halogen bonding, Roche, X-ray data
13 Comments
Review: Gamma-secretase modulators
An excellent review titled ‘γ-Secretase Modulators as Potential Disease Modifying Anti-Alzheimer’s Drugs’ has recently published in J.Med.Chem. The review gives some background to the disease and to the generally, although not universally, accepted hypothesis that amyloid plays a key role … Continue reading
Posted in Enzyme Inhibitors, Reviews
Tagged Alzheimer's disease, amyloid, beta-secretase, Chiesi, E-2012, Eisai, gamma-secretase, γ-Secretase, review
1 Comment
Discovery of Rivaroxaban (Factor Xa Inhibitor)
The discovery of novel anticoagulants, and the search for novel orally active agents in particular, has been a long and difficult journey. However, the recent (2008) launches of Bayer’s Factor Xa inhibitor (Rivaroxaban, BAY 59-7939) and Boehringer Ingelheim’s Thrombin inhibitor … Continue reading
Discovery of LX2931 (Sphingosine 1-Phosphate Lyase Inhibitor) & Phase IIa Data
Fingolimod (FTY720, Gilenya), an immunosuppresive agent with activity purported to be mediated by binding of it’s phosphorylated derivative to the sphingosine-1-phosphate receptor 1 (S1P1), was approved earlier in the year as the first orally administered disease modifying therapy for the treatment … Continue reading
Discovery of PF-04457845 (FAAH Inhibitor)
In this latest publication from the Pfizer labs, the authors describe their continuing efforts to identify urea-based, irreversible inhibitors of fatty acid amide hydrolase (FAAH). Inhibition of FAAH and the concomitant elevation of endogenous levels of fatty acid amides has … Continue reading
Posted in Clinical Candidates, Enzyme Inhibitors
Tagged Analgesic, CYP450, FAAH, Fatty acid amide hydrolase, osteoarthritis, Pain, PF-04457845, PF-3845, Pfizer, Phase II, POC, PSA
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