P2Y1 receptor antagonists as novel antithrombotic agents.

The P2Y(1) and P2Y(12) purinergic receptors are responsible for mediating adenosine diphosphate (ADP) dependent platelet aggregation. Evidence from P2Y(1) knockout studies as well as from nucleotide-based small molecule P2Y(1) antagonists has suggested that the antagonism of this receptor may offer a novel and effective method for the treatment of thrombotic disorders. Herein, we report the identification and optimization of a series of non-nucleotide P2Y(1) antagonists that are potent and orally bioavailable.

Comparison of commercially available genetic algorithms: gas as variable selection tool.

Many commercially available software programs claim similar efficiency and accuracy as variable selection tools. Genetic algorithms are commonly used variable selection methods where most relevant variables can be differentiated from 'less important' variables using evolutionary computing techniques. However, different vendors offer several algorithms, and the puzzling question is: which one is the appropriate method of choice? In this study, several genetic algorithm tools (e.

Prediction of HPLC conditions using QSPR techniques: an effective tool to improve combinatorial library design.

The purification and characterization of compounds resulting from parallel synthesis or combinatorial chemistry has not yet been optimized to operate as a completely automated high-throughput process. Liquid chromatography/mass spectroscopy (LC/MS) is most commonly employed to carry out the characterization and identification of combinatorial compounds. This desired level of automation can only be accomplished if the separation conditions for every compound in the combinatorial array are known prior to the analysis.

Prediction of drug-like molecular properties: modeling cytochrome p450 interactions.

Preventing drug-drug interactions and reducing drug-related mortalities dictate cleaner and costlier medicines. The cost to bring a new drug to market has increased dramatically over the last 10 years, with post-discovery activities (preclinical and clinical) costs representing the majority of the spend. With the ever-increasing scrutiny that new drug candidates undergo in the post-discovery assessment phases, there is increasing pressure on discovery to deliver higher-quality drug candidates.

Quantitative chirality analysis of molecular subunits of bis(oxazoline)copper(II) complexes in relation to their enantioselective catalytic activity.

The analysis of the quantitative chirality of molecular subunits of spirocyclic bisoxazoline copper complexes was carried out in order to identify the molecular portions most responsible for the chirality of the whole molecule, and therefore also for its catalytic enantioselectivity. It is shown that the smallest fragment that carries the information on molecular chirality contains only a portion of the bidentate bisoxazoline ligands and most atoms of the two monodentate ligands. The structural parameters that are best correlated to the chirality measures of the studied systems are the bond angles at the bridgehead spiro-carbon atom.

Ligand distortion modes leading to increased chirality content of Katsuki-Jacobsen catalysts.

The "chirality content" of Katsuki-Jacobsen epoxidation catalysts are computed with the Avnir continuous chirality measure (CCM). An assessment of Mn(salen) molecules from the Cambridge Structural Database shows there exist some variation in CCM and the chirality content for several triplet state complexes of these catalysts purported in the literature to be the active species show even larger CCM values. Several deformation modes were analyzed to examine how chirality content changes as catalyst distortion is induced.

Elucidation of the chiral recognition mechanism of cinchona alkaloid carbamate-type receptors for 3,5-dinitrobenzoyl amino acids.

A cinchona alkaloid having extraordinary chiral discriminatory powers (alpha = 32.6 for dinitrobenzoyl leucine) is developed as a chiral stationary phase (CSP) for chromatography. An explanation of how chiral discrimination takes place is presented.