Abstract: Steric features inherent in the three dimensional disposition of atoms in molecules can be represented as multiplets using a defined set of steric descriptors. The resulting multiplets can be encoded in a compressed form of bitstring known as a bitmap. Such bitmaps can be generated in compressed form and used to compare individual conformers or ensembles of conformers of molecules to each other without decompression. Such comparisons are useful in molecular similarity analysis, in molecular diversity analysis, in database searching, and in conformational analysis.

Abstract: The use for biological screening purposes of a subset (library) of a large combinatorially accessible chemical universe increases the efficiency of the screening process only if the subset contains members representative of the total diversity of the universe. In order to insure inclusion in the subset of molecules representing the total diversity of the universe under consideration, valid molecular descriptors which quantitatively reflect the diversity of the molecules in the universe are required. A unique validation method is used to examine both a new three dimensional steric metric and some prior art metrics. With this method, the relative usefulness/validity of individual metrics can be ascertained from their application to randomly selected literature data sets.

Abstract: The distribution of chemical compounds in high-dimensional molecular descriptor space can be viewed in two dimensions by applying the projection method of this invention. This method has particular usefulness for viewing the relationships of a large number of compounds such as found in a large scale HTS or virtual combinatorial library. After selecting a representative subset of the larger data set of comounds, initially components from the high-dimensional descriptor space are determined by PCA. In order to relax an NLM projection using the PCA components as a start, the stress function is modified to reflect a local horizon beyound which the separation of the compounds is not meaningfully measureable. The resulting two dimensional projections provide a clear insight into the distribution of the chemical compounds in the higher dimensional space.

Abstract: The method of this invention identifies distinctive items of information from a larger body of information on the basis of similarities or dissimilarities among the items and achieves a significant increase in speed as well as the ability to balance the representativeness and diversity among the identified items by applying selection criteria to randomly chosen subsamples of all the information. The method is illustrated with reference to the compound selection requirements of medicinal chemists. Compound selection methods currently available to chemists are based on maximum or minimum dissimilarity selection or on hierarchical clustering. The method of the invention is more general and incorporates maximum and minimum dissimilarity-based selection as special cases. In addition, the number of iterations required to select the items is a multiple of the group size which, at its greatest, is approximately the square root of the population size.

Abstract: The problem of how to select out of a large chemically accessible universe molecules representative of the diversity of that universe is resolved by the discovery of a method to validate molecular structural descriptors. Using the validated descriptors, optimally diverse subsets can be selected. In addition, from the universe, molecules with characteristics similar to a selected molecule can be identified. The validated descriptors also enable the generation of a huge virtual library of potential product molecules which could be formed by combinatorial arrangement of structural variations and cores. In this virtual library it is possible to search billions of possible product compounds in relatively short time frames.

Abstract: A new computer implemented method for discovering structure-activity relationships has been discovered which utilizes weighted 2D fingerprints in conjunction with the PLS statistical methodology. This method produces a robust QSAR technique that can be automated. In addition, the MOLECULAR HOLOGRAM QSAR technique generates high quality QSAR models that are in many cases as good as or better than models arising from use of more complex and time consuming techniques such as CoMFA or Apex-3D.

Abstract: The use of biological screening purposes of a subset (library) of a large combinatorially accessible chemical universe increases the efficiency of the screening process only if the subset contains members representative of the total diversity of the universe. In order to insure inclusion in the subset of molecules representing the total diversity of the universe under consideration, valid molecular descriptors which quantitatively reflect the diversity of the molecules in the universe are required. A unique validation method is used to examine both a new three dimensional steric metric and some prior art metrics. With this method, the relative usefulness/validity of individual metrics can be ascertained from their application to randomly selected literature data sets.

Abstract: Disclosed herein is a new class of pyrazole compounds which act at the 5HT.sub.2A receptors.

Abstract: A new computer implemented method for discovering structure-activity relationships has been discovered which utilizes weighted 2D fingerprints in conjunction with the PLS statistical methodology. This method produces a robust QSAR technique that can be automated. In addition, the MOLECULAR HOLOGRAM QSAR technique generates high quality QSAR models that are in many cases as good as or better than models arising from use of more complex and time consuming techniques such as CoMFA or Apex-3D.