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: 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: Comparative Molecular Field Analysis (CoMFA) is an effective computer implemented methodology of 3D-QSAR employing both interactive graphics and statistical techniques for correlating shapes of molecules with their observed biological properties. For each molecule of a series of known substrates the steric and electrostatic interaction energies with a test probe atom are calculated at spatial coordinates around the molecule. Subsequent analysis of the data table by a partial least squares (PLS) cross-validation technique yields a set of coefficients which reflect the relative contribution of the shape elements of the molecular series to differences in biological activities. Display in three dimensions in an interactive graphics environment of the spatial volumes highly associated with biological activity, and comparison with molecular structures yields an understanding of intermolecular associations. CoMFA will also predict the biological activity of new molecular species.

Abstract: Comparative Molecular Field Analysis (CoMFA) is an effective computer implemented methodology of 3D-QSAR employing both interactive graphics and statistical techniques for correlating shapes of molecules with their observed biological properties. For each molecule of a series of known substrates the steric and electrostatic interaction energies with a test probe atom are calculated at spatial coordinates around the molecule. Subsequent analysis of the data table by a partial least squares (PLS) cross-validation technique yields a set of coefficients which reflect the relative contribution of the shape elements of the molecular series to differences in biological activities. Display in three dimensions in an interactive graphics environment of the spatial volumes highly associated with biological activity, and comparison with molecular structures yields an understanding of intermolecular associations. CoMFA will also predict the biological activity of new molecular species.

Abstract: A method is provided for converting a carboxylic acid amide to a carboxylic acid ester by reacting a vaporized mixture of the amide and an aliphatic alcohol or a phenol in the presence of a suitable catalyst at temperatures of from 100.degree. C. to 400.degree. C. The process is especially useful for the conversion of methacrylamide to methyl methacrylate.

Abstract: This invention relates to a new class of indicator dyes useful as optical filter agents in photographic processes to protect a selectively exposed photosensitive material from further exposure during processing in the presence of incident light. Such dyes comprise 3,6-disubstituted carbazoles wherein the 3,6 substituents are selected from a phthalidyl radical, C.sub.6 H.sub.4.CO.O.CR--, wherein R is an aryl group and an o-carboxybenzoyl radical, not more than one of said substituents being o-carboxybenzoyl.