Biomedical subjects

P Selzer

Publications and source records attributed to P Selzer.

6 recordsLinked to original sources

PubMed2002

Decision support systems for chemical structure representation, reaction modeling, and spectra simulation.

The choice of an appropriate structure coding scheme is the secret to success in QSAR studies. Depending on the problem at hand, 2D or 3D descriptors have to be chosen; the consideration of electronic effects might be crucial, conformational flexibility has to be of special concern. Artificial neural networks, both with unsupervised and with supervised learning schemes, are powerful tools for establishing relationships between structure and physical, chemical, or biological properties. The EROS system for the simulation of chemical reactions is briefly presented and its application to the degradation of s-triazine herbicides is shown. It is further shown how the simulation of chemical reactions can be combined with the simulation of infrared spectra for the efficient identification of the structure of degradation products.

Decision Support Techniques↗

PubMed2001

A combined application of reaction prediction and infrared spectra simulation for the identification of degradation products of s-triazine herbicides.

Substance identification in analytical chemistry is usually performed by comparing an experimental spectrum with a reference spectrum. Especially in environmental chemistry, reference spectra from databases are only available for a limited number of compounds. The combination of the reaction prediction system EROS and of infrared spectra simulation is a powerful tool for computer-assisted substance identification. First, possible degradation products of a chemical are predicted and then the infrared spectra of all these compounds are simulated. Comparison of the simulated infrared spectra with experimental spectra allows one to identify the structure of compounds. The method is demonstrated with the example of s-triazine herbicides.

Computer Simulation↗

PubMed2000

Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties.

Molecular polar surface area (PSA), i.e., surface belonging to polar atoms, is a descriptor that was shown to correlate well with passive molecular transport through membranes and, therefore, allows prediction of transport properties of drugs. The calculation of PSA, however, is rather time-consuming because of the necessity to generate a reasonable 3D molecular geometry and the calculation of the surface itself. A new approach for the calculation of the PSA is presented here, based on the summation of tabulated surface contributions of polar fragments. The method, termed topological PSA (TPSA), provides results which are practically identical with the 3D PSA (the correlation coefficient between 3D PSA and fragment-based TPSA for 34 810 molecules from the World Drug Index is 0.99), while the computation speed is 2-3 orders of magnitude faster. The new methodology may, therefore, be used for fast bioavailability screening of virtual libraries having millions of molecules. This article describes the new methodology and shows the results of validation studies based on sets of published absorption data, including intestinal absorption, Caco-2 monolayer penetration, and blood-brain barrier penetration.

Biological Availability↗

PubMed2000

Rapid access to infrared reference spectra of arbitrary organic compounds: scope and limitations of an approach to the simulation of infrared spectra by neural networks

Substance identification by infrared spectroscopy is performed by comparison of the experimental spectrum with a reference spectrum from a printed compilation or a database. If the analyzed compound can not be found in a database the corresponding reference spectrum has to be simulated. In order to achieve this, several reasonable candidates of structures for the compound at hand have to be conceived and for all these, infrared spectra have to be developed. The simulated spectrum that is most similar to the experimental suggests the correct structure. A rapid spectrum prediction method based on neural networks has been developed that supplies reference spectra for any organic compound. The scope and limitations of this method will be discussed on a test set of 16 compounds representing a broad range of organic chemistry.

Journal Article↗

PubMed1991

Occlusive peripheral vascular disease: a multicenter trial of fluorescence-guided, pulsed dye laser-assisted balloon angioplasty.

Fluorescence-guided, laser-assisted balloon angioplasty was performed in 129 patients with iliac and femoropopliteal artery chronic occlusions (range, 0.5-50.0 cm; mean length, 9.9 cm) after failure of recanalization with standard guide-wire techniques. Laser recanalization and short-term angiographic success were achieved in 101 (72%) and 95 (68%) of 140 occlusions, respectively. Laser and balloon angioplasty failures were encountered in heavily calcified plaques or after perforations and dissections. Complications included perforations (19%), hematomas (5%), thromboses (4%), and distal embolizations (4%). Real-time fluorescence spectroscopy identified thrombus, white fibrous plaque, and media but could not avoid perforations in many cases because laser wire advancement outdistanced fluorescence sensing. Disruption of tissue by means of pressure transients and/or mechanical advancement occurred in at least 36% of lesions where the laser energy was insufficient (less than 0.4 J/cm) to ablate significant tissue. Integration of fluorescence guidance with pulsed dye laser ablation is feasible, but additional refinements are necessary to increase safety and efficacy.

Adult↗

PubMedDate not supplied

Web-based cheminformatics and molecular property prediction tools supporting drug design and development at Novartis.

Web-based tools offer many advantages for processing chemical information, most notably ease of use and high interactivity. Therefore more and more pharmaceutical companies are using web technology to deliver sophisticated molecular processing tools directly to the desks of their chemists, to assist them in the process of designing and developing new drugs. In this paper, the web-based cheminformatics system developed at Novartis and currently used by more than thousand users is described. The system allows various molecular modeling and molecular processing tasks, including the calculation of molecular and substituent properties, property-based virtual screening, visualization of molecules, bioisosteric design, diversity analysis, and support of combinatorial chemistry. The methodology to calculate various molecular properties relevant to drug design is described, including the prediction of intestinal absorption, blood-brain barrier penetration, efflux, and water solubility. Information about the web technology used is also provided.

Drug Design↗