piperidines has been researched along with farnesyl-pyrophosphate* in 2 studies
2 other study(ies) available for piperidines and farnesyl-pyrophosphate
| Article | Year |
|---|---|
Synthesis of novel 4,1-benzoxazepine derivatives as squalene synthase inhibitors and their inhibition of cholesterol synthesis.
Modification of the carboxyl group at the 3-position and introduction of protective groups to the hydroxy group of the 4,1-benzoxazepine derivative 2 (metabolite of 1) were carried out, and the inhibitory activity for squalene synthase and cholesterol synthesis in the liver was investigated. Among these compounds, the glycine derivative 3a and beta-alanine derivative 3f exhibited the most potent inhibition of squalene synthase prepared from HepG2 cells (IC(50) = 15 nM). On the other hand, the piperidine-4-acetic acid derivative 4a, which was prepared by acetylation of 3j, was the most effective inhibitor of cholesterol synthesis in rat liver (ED(50) = 2.9 mg/kg, po). After oral administration, 4a was absorbed and rapidly hydrolyzed to deacylated 3j. Compound 3j was detected mainly in the liver, but the plasma level of 3j was found to be low. Compounds 3j and 4a were found to be competitive inhibitors with respect to farnesyl pyrophosphate. Further evaluation of 4a as a cholesterol-lowering and antiatherosclerotic agent is underway. Topics: Animals; Anticholesteremic Agents; Azepines; Cholesterol; Enzyme Inhibitors; Farnesyl-Diphosphate Farnesyltransferase; Humans; Liver; Male; Oxazepines; Piperidines; Polyisoprenyl Phosphates; Rats; Rats, Wistar; Sesquiterpenes; Structure-Activity Relationship | 2002 |
Hydrophobicity at the surface of proteins.
A new method is presented to quantitatively estimate and graphically display the propensity of nonpolar groups to bind at the surface of proteins. It is based on the calculation of the binding energy, i.e., van der Waals interaction plus protein electrostatic desolvation, of a nonpolar probe sphere rolled over the protein surface, and on the color coding of this quantity on a smooth molecular surface (hydrophobicity map). The method is validated on ten protein-ligand complexes and is shown to distinguish precisely where polar and nonpolar groups preferentially bind. Comparisons with existing approaches, like the display of the electrostatic potential or the curvature, illustrate the advantages and the better predictive power of the present method. Hydrophobicity maps will play an important role in the characterization of binding sites for the large number of proteins emerging from the genome projects and structure modeling approaches. Topics: Alkyl and Aryl Transferases; Annexin A2; Binding Sites; Dipeptides; DNA; DNA-Binding Proteins; Farnesyltranstransferase; Homeodomain Proteins; Macromolecular Substances; Models, Molecular; Nuclear Proteins; Peptides; Piperidines; Polyisoprenyl Phosphates; Pre-B-Cell Leukemia Transcription Factor 1; Protein Binding; Protein Conformation; Protein Structure, Quaternary; Proteins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-mdm2; S100 Proteins; Sesquiterpenes; Static Electricity; Surface Properties; Thermodynamics; Thrombin; Tumor Suppressor Protein p53 | 1999 |