Abstract: Thromboresistant materials are described which incorporate pyrazinone compounds of the Formula I: wherein X is O, NR11 or CH═N, R3-R11, Ra, Rb, Rc, W, m, and n are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof. The compounds of the invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin. Compositions for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation are described.

Abstract: Disclosed is a method for treating the symptoms of an acute or chronic disorder mediated by the classical pathway of the complement cascade, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula I or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein R1, R2, R3, R4, X, Y and Z are defined in the specification.

Abstract: The present invention relates to novel substituted benzofurans and benzothiophenes compounds that are antagonists of alpha V (&agr;v) integrins, for example &agr;v&bgr;3 and &agr;v&bgr;5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The compounds may be used in the treatment of pathological conditions mediated by &agr;v&bgr;3 and &agr;v&bgr;5 integrins, including such conditions as tumor growth, metastasis, restenosis, osteoporosis, inflammation, macular degeneration, diabetic retinopathy, and rheumatoid arthritis.

Abstract: An automatic, partially automatic, and/or manual iterative system, method and/or computer program product for generating chemical entities having desired or specified physical, chemical, functional, and/or bioactive properties. The present invention identifies a set of compounds for analysis; collects, acquires or synthesizes the identified compounds; analyzes the compounds to determine one or more physical, chemical and/or bioactive properties (structure-property data); and uses the structure-property data to identify another set of compounds for analysis in the next iteration. An Experiment Planner generates Selection Criteria and/or one or more Objective Functions for use by a Selector. The Selector searches the Compound Library to identify a subset of compounds (a Directed Diversity Library) that maximizes or minimizes the Objective Functions. The compounds listed in the Directed Diversity Library are then collected, acquired or synthesized, and are analyzed to evaluate their properties of interest.

Abstract: The present invention is directed to inhibiting pest GABA receptors by contacting said receptors with a compound of Formula I: The invention is also directed to methods of controlling pests, especially insects and arachnids such as fleas and ticks, and to novel compounds within the scope of Formula I.

Abstract: Disclosed is a method for treating the symptoms of an acute or chronic disorder mediated by the classical pathway of the complement cascade, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula I or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein R1, R2, R3, R4, X, Y and Z are defined in the specification.

Abstract: A microtiter plate system includes an integral heater. In an embodiment, the integral heater includes a heater plate. In another embodiment, the integral heater includes resistive heater wires positioned beneath and/or between the wells of a microtiter plate. In an embodiment, the microtiter plate system includes optically clear well bottoms that permit sensing and measurement of samples through the optically clear well bottoms. In an implementation, an optically clear heater is positioned beneath the optically clear well bottoms. In an alternative implementation, resistive heater wires are positioned between the wells. In an embodiment, the microtiter plate system includes a microtiter plate lid with an integral heater, which can be implemented using a heater plate, resistive wires, and the like.

Abstract: The present invention relates to novel tetrahydroisoquinoline-3-carboxylic acid alkoxyguanidine compounds that are antagonists of alpha V (&agr;v) integrins, for example &agr;v&bgr;3 and &agr;v&bgr;5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof.

Abstract: The present invention relates to novel substituted indole compounds that are antagonists of alpha V (&agr;v) integrins, for example &agr;v&bgr;3 and &agr;v&bgr;5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The compounds may be used in the treatment of pathological conditions mediated by &agr;v&bgr;3 and &agr;v&bgr;5 integrins, including such conditions as tumor growth, metastasis, restenosis, osteoporosis, inflammation, macular degeneration, diabetic retinopathy, and rheumatoid arthritis.

Abstract: Cyclic oxyguanidine pyrazinone compounds are described, including compounds of the Formula I: wherein R3, R4, R5, W, and A are as set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof. The compounds of the invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin. Compositions for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation are described.

Abstract: Aminoguanidine and alkoxyguanidine compounds are described, including compounds of the Formula VII: wherein X is O or NR9 and Het, R1, R7, R8, R12-R15, Ra, Rb, Rc, Z, and n are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin. Also described are methods for preparing such compounds. The compounds of the invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin. The invention includes a composition for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation in a mammal, comprising a compound of the invention in a pharmaceutically acceptable carrier.

Abstract: The present invention is directed to non-peptidic factor Xa inhibitors which are useful for the treatment of arterial and venous thrombotic occlusive disorders, inflammation, cancer, and neurodegenerative diseases. The factor Xa inhibitors provide compounds having Formula I: or pharmaceutically acceptable salts thereof; wherein Q is phenyl, benzyl, pyridyl, thienyl, indolyl, quinolinyl, benzothienyl, biphenylyl, or imidazolyl; any of which can include one or more optional substituents independently selected from halo, trifluoromethyl, hydroxy, amino, nitro, cyano, C1-3 alkoxy, C1-3 alkyl, methylenedioxy, carboxamido, acetamido, or amidino; X is methylene, carbonyl, or sulfonyl; Z is methylene, ethylene, or propylene; M is methylene or ethylene; and R1 R2 and R3 are independently hydrogen or C1-3 alkyl.

Abstract: A system, method and computer program product for representing precise or imprecise measurements of similarity/dissimilarity (relationships) between objects as distances between points in a multi-dimensional space that represents the objects. Self-organizing principles are used to iteratively refine an initial (random or partially ordered) configuration of points using stochastic relationship/distance errors. The data can be complete or incomplete (i.e. some relationships between objects may not be known), exact or inexact (i.e. some or all of the relationships may be given in terms of allowed ranges or limits), symmetric or asymmetric (i.e. the relationship of object A to object B may not be the same as the relationship of B to A) and may contain systematic or stochastic errors. The relationships between objects may be derived directly from observation, measurement, a priori knowledge, or intuition, or may be determined indirectly using any suitable technique for deriving proximity (relationship) data.

Abstract: A computer based, iterative process for generating chemical entities with defined physical, chemical and/or bioactive properties. During each iteration of the process, (1) a directed diversity chemical library is robotically generated in accordance with robotic synthesis instructions; (2) the compounds in the directed diversity chemical library are analyzed to identify compounds with the desired properties; (3) structure-property data are used to select compounds to be synthesized in the next iteration; and (4) new robotic synthesis instructions are automatically generated to control the synthesis of the directed diversity chemical library for the next iteration.

Abstract: A method, system, and computer product is presented for mapping a set of patterns into an m-dimensional space so as to preserve relationships that may exist between these patterns. A subset of the input patterns is chosen and mapped into the m-dimensional space using an iterative nonlinear mapping process based on subset refinements. A set of n attributes are determined for each pattern, and one or more neural networks or other supervised machine learning techniques are then trained in accordance with the mapping produced by the iterative process. Additional input patterns not in the subset are mapped into the m-dimensional space by determining their n input attributes and using the neural networks in a feed-forward (prediction) mode.

Abstract: A microtiter plate system includes an integral heater. In an embodiment, the integral heater includes a heater plate. In another embodiment, the integral heater includes resistive heater wires positioned beneath and/or between the wells of a microtiter plate. In an embodiment, the microtiter plate system includes optically clear well bottoms that permit sensing and measurement of samples through the optically clear well bottoms. In an implementation, an optically clear heater is positioned beneath the optically clear well bottoms. In an alternative implementation, resistive heater wires are positioned between the wells. In an embodiment, the microtiter plate system includes a microtiter plate lid with an integral heater, which can be implemented using a heater plate, resistive wires, and the like.

Abstract: Ketothiazole alkoxyguanidine and aminoguanidine analogs are described, including compounds of the Formula I: wherein X is O or NR9 and Het, A, R1, R7, R8, R12, R13, Ra, Rb, Rc, Z, m and n are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin. Also described are methods for preparing such compounds. The compounds of the invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin. The invention includes a composition for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation in a mammal, comprising a compound of the invention in a pharmaceutically acceptable carrier.

Abstract: An automatic, partially automatic, and/or manual iterative system, method and/or computer program product for generating chemical entities having desired or specified physical, chemical, functional, and/or bioactive properties. The present invention identifies a set of compounds for analysis; collects, acquires or synthesizes the identified compounds; analyzes the compounds to determine one or more physical, chemical and/or bioactive properties (structure-property data); and uses the structure-property data to identify another set of compounds for analysis in the next iteration. An Experiment Planner generates Selection Criteria and/or one or more Objective Functions for use by a Selector. The Selector searches the Compound Library to identify a subset of compounds (a Directed Diversity Library) that maximizes or minimizes the Objective Functions. The compounds listed in the Directed Diversity Library are then collected, acquired or synthesized, and are analyzed to evaluate their properties of interest.

Abstract: The present invention is directed to aminoguanidine and alkoxyguanidine compounds, including compounds of Formula I: wherein X is O or NR19 and A1, A2, R7-R10, R18, Ra, Rb, Rc, n and m are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin. Also described are methods for preparing the compounds of Formula I. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin, or are intermediates useful for forming compounds having antithrombotic activity. The invention includes a composition for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation in a mammal.

Abstract: Amidino and benzamidino compounds, including compounds of the formula: wherein R1-R4, R6-R9, Y, Z, n and m are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit a number of proteolytic enzymes are described. Also described are methods for preparing the compounds of Formula I.