pf-03654746 has been researched along with Lipidoses* in 1 studies
1 other study(ies) available for pf-03654746 and Lipidoses
| Article | Year |
|---|---|
Discovery of two clinical histamine H(3) receptor antagonists: trans-N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidinylmethyl)phenyl]cyclobutanecarboxamide (PF-03654746) and trans-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]-N-(2-methylpropyl)cyclobuta
The discovery of two histamine H(3) antagonist clinical candidates is disclosed. The pathway to identification of the two clinical candidates, 6 (PF-03654746) and 7 (PF-03654764) required five hypothesis driven design cycles. The key to success in identifying these clinical candidates was the development of a compound design strategy that leveraged medicinal chemistry knowledge and traditional assays in conjunction with computational and in vitro safety tools. Overall, clinical compounds 6 and 7 exceeded conservative safety margins and possessed optimal pharmacological and pharmacokinetic profiles, thus achieving our initial goal of identifying compounds with fully aligned oral drug attributes, "best-in-class" molecules. Topics: Animals; Blood Proteins; Blood-Brain Barrier; Cell Line; Cyclobutanes; Dogs; Drinking Behavior; Drug Design; High-Throughput Screening Assays; Histamine Antagonists; Humans; In Vitro Techniques; Kidney; Lipidoses; Lung; Microsomes, Liver; Models, Molecular; Molecular Structure; Phospholipids; Protein Binding; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptors, Histamine H3; Stereoisomerism; Structure-Activity Relationship | 2011 |