Abstract: A method for computational drug design using an evolutionary algorithm, comprises evaluating virtual molecules according to vector distance (VD) to at least one achievement objective that defines a desired ideal molecule. In one method the invention comprises defining a set of n achievement objectives (OA1-n), where n is at least one; defining a population (PG=0) of at least one molecule; selecting an initial population (Pparent) of at least one molecule (I1-In) from the population (PG=0); and evaluating members (I1-In) of the initial population (Pparent) against at least one of the n achievement objectives (OA1-x), where x is from 1 to n.

Abstract: A method for computational drug design using an evolutionary algorithm, comprises evaluating virtual molecules according to vector distance (VD) to at least one achievement objective that defines a desired ideal molecule. In one method the invention comprises defining a set of n achievement objectives (OA1-n), where n is at least one; defining a population (PG=0) of at least one molecule; selecting an initial population (Pparent) of at least one molecule (I1-In) from the population (PG=0); and evaluating members (I1-In) of the initial population (Pparent) against at least one of the n achievement objectives (OA1-x), where x is from 1 to n.

Abstract: A method for computational drug design using an evolutionary algorithm, comprises evaluating virtual molecules according to vector distance (VD) to at least one achievement objective that defines a desired ideal molecule. In one method the invention comprises defining a set of n achievement objectives (OA1-n), where n is at least one; defining a population (PG=0) of at least one molecule; selecting an initial population (Pparent) of at least one molecule (I1-In) from the population (PG=0); and evaluating members (I1-In) of the initial population (Pparent) against at least one of the n achievement objectives (OA1-x), where x is from 1 to n.

Abstract: The invention relates to morpholino-derivatives according to Formula (I) or stereoisomers or pharmaceutically acceptable salts or solvate thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, m and n are as defined in the specification. The compounds are antagonists, reverse agonists or agonists of G-protein coupled receptors, such as dopamine D4 and 5HT1a. The inventions also relates to pharmaceutical compositions comprising the compounds and methods involving the compounds and compositions. The compounds and compositions of the invention may in particular be used in the treatment of diseases and disorders, such as neurological and neurodegenerative diseases; or as lead compounds for the design and selection of further therapeutic compounds.

Abstract: The invention relates to morpholino-derivatives according to Formula (I) or stereoisomers or pharmaceutically acceptable salts or solvate thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, m and n are as defined in the specification. The compounds are antagonists, reverse agonists or agonists of G-protein coupled receptors, such as dopamine D4 and 5HT1a. The inventions also relates to pharmaceutical compositions comprising the compounds and methods involving the compounds and compositions. The compounds and compositions of the invention may in particular be used in the treatment of diseases and disorders, such as neurological and neurodegenerative diseases; or as lead compounds for the design and selection of further therapeutic compounds.

Abstract: A method for computational drug design using an evolutionary algorithm, comprises evaluating virtual molecules according to vector distance (VD) to at least one achievement objective that defines a desired ideal molecule. In one method the invention comprises defining a set of n achievement objectives (OA1-n), where n is at least one; defining a population (PG=0) of at least one molecule; selecting an initial population (Pparent) of at least one molecule (I1?In) from the population (PG=0); and evaluating members (I1?In) of the initial population (Pparent) against at least one of the n achievement objectives (OA1-x), where x is from 1 to n.

Abstract: The present invention relates to a CCR5 antagonist compound for elevating high density lipoprotein (HDL) particles in a patient, improving plasma lipid profile in a patient or reducing triglycerides in a patient. The invention also relates to a pharmaceutical composition comprising a CCR5 antagonist compound, an HMG-CoA reductase inhibitor compound and a pharmaceutically acceptable carrier. The invention also relates to a pharmaceutical composition comprising a CCR5 antagonist compound, a cholesteryl ester transfer protein (CETP) inhibitor compound and a pharmaceutically acceptable carrier.

Abstract: An assay method for determining binding of a test compound to pyruvate dehydrogenase kinase (PDHK) at a given site comprising determining (a) the degree of polarisation of the light emitted by a PDHK complex formed by contacting in solution a known concentration of PDHK with a known concentration of a fluorescent compound known to bind to PDHK at that site, and (b) the degree of polarisation of the light emitted by a PDHK complex formed by contacting in solution the test compound, the same concentration of PDHK and the same concentration of the fluorescent compound, a lesser value of the degree of polarisation (b) than that of (a) being taken as indicative of binding of the test compound to that site.

Abstract: The present invention relates to the soakable crystal structures of a phosphodiesterase 5 (PDE5) and their uses in identifying PDE5 ligands, including PDE5 inhibitor compounds. The present invention also relates to methods of identifying such PDE5 inhibitor compounds and their medical use. The present invention additionally relates to crystals of PDE5 into which ligands may be soaked and crystals of PDE5 comprising PDE5 ligands that have been soaked into the crystal.

Abstract: The present invention relates to quinolone compounds and their use in the treatment of viral infections.