Abstract: The disclosures herein relate to novel compounds of formula wherein R1, R2, R3 and R4 and n are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of inflammation, neurological or psychiatric disorders associated with modulating mGlu5 receptor function.

Abstract: The present application relates to certain substituted imidazole and triazole compounds, pharmaceutical compositions containing them, and methods of using them, including methods for treating pain, musculoskeletal inflammation, neuroinflammatory disorders, airway inflammation, itch, dermatitis, colitis and related conditions. The compounds are of Formula (I) where X is N or CH, Z and Y are N or C (but both not N) and R1-R3 are as defined herein.

Abstract: This invention relates to compounds that are agonists of the muscarinic M4 receptor and/or M4 receptor and which are useful in the treatment of muscarinic M1/M4 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds include those according to formula 1a or a salt thereof, wherein n, p, Q, R1, R2, R3, R9 and R4 are as defined herein.

Abstract: The invention provides an assay for assessing the conformational stability of a membrane protein, comprising: (a) providing a sample comprising a first population and a second population of a membrane protein; wherein the membrane protein in the first population is labelled with a donor label and the membrane protein in the second population is labelled with an acceptor label, or the membrane protein in the first population is labelled with an acceptor label and the membrane protein in the second population is labelled with a donor label, (b) exposing the first and second populations of the membrane protein to a stability modulating agent and/or condition, (c) and assessing aggregation between membrane proteins of the first and second populations by activating the donor label to permit a distance-dependent interaction with the acceptor label, which interaction produces a detectable signal.

Abstract: This invention relates to compounds that are agonists of the muscarinic M1 receptor and which are useful in the treatment of muscarinic M1 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula where m, p, q, W, Z, Y, X1, X2, R1, R2, R3 and R4 are as defined herein.

Abstract: This invention relates to compounds that are agonists of the muscarinic M1 receptor and which are useful in the treatment of muscarinic M1 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula I, where n is 1 or 2; p is 0, 1 or 2; q is 0, 1 or 2; and R1-R6 are as defined herein.

Abstract: This invention relates to compounds that are agonists of the muscarinic M1 receptor and/or M4 receptor and which are useful in the treatment of muscarinic M1/M4 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds include those according to formula 1, or a salt thereof wherein Q, R1, R2, R3 and R4 are as defined herein.

Abstract: The invention relates to mutant G-protein coupled receptors with increased conformational stability, and methods of use thereof. In some aspects, polynucleotides encoding the mutant G-protein coupled receptors are provided. In some aspects, host cells comprising the polynucleotides are provided. In some aspects, the invention relates to crystallized forms of the mutant G-protein coupled receptors, and methods of preparing the same.

Abstract: This invention relates to compounds that are agonists of the muscarinic M1 receptor and/or M4 receptor and which are useful in the treatment of muscarinic M1/M4 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds include those according to formula (1a) or a salt thereof, wherein p, q, r, s, Q, R3 and R4 are as defined herein.

Abstract: This invention relates to compounds that are agonists of the muscarinic M1 and/or M4 receptor and which are useful in the treatment of diseases mediated by the muscarinic M1 and M4 receptors. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula where X1; X2; R1 and R4 are as defined herein.

Abstract: The disclosures herein relate to novel compounds of formula wherein W, X and Y1, Y2, Y3 and Y4 are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of neurological or psychiatric disorders associated with orexin receptors.

Abstract: The disclosures herein relate to novel compounds of formula wherein R1, R2, R3 and R4 are as defined herein, and their use in treating, preventing, ameliorating, controlling or reducing cerebrovascular or vascular disorders associated with CGRP receptor function.

Abstract: The present application relates to certain substituted imidazole and triazole compounds, pharmaceutical compositions containing them, and methods of using them, including methods for treating pain, musculoskeletal inflammation, neuroinflammatory disorders, airway inflammation, itch, dermatitis, colitis and related conditions. The compounds are of Formula (I) where X is N or CH, Z and Y are N or C (but both not N) and R1-R3 are as defined herein.

Abstract: The invention provides a fusion protein comprising, from N-terminus to C-terminus: a) a first portion of a Family B G-protein coupled receptor (GPCR) that comprises transmembrane helix (TM)-1, TM2 and TM3 of the GPCR; b) a stable protein domain; and c) a second portion of the GPCR comprising TM4, TM5, TM6 and TM7 of the GPCR. The invention also provides a method of crystallising a GPCR comprising providing the fusion protein of the invention and crystallising it to obtain crystals.

Abstract: This invention relates to compounds (Formula (1)) that are agonists of the muscarinic M1 receptor and which are useful in the treatment of muscarinic M1 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula where R1-R5, X1, X2 and p are as defined herein.

Abstract: This invention relates to compounds that are agonists of the muscarinic M1 receptor or M1 and M4 receptors and which are useful in the treatment of muscarinic M1 or M1/M4 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula wherein Q4, Q5, R5, p, V, Q1, Q2, X1, X2 and W are defined herein.

Abstract: The disclosures herein relate to novel compounds of formula wherein R1, R2 and R3 are as defined herein, and their use in treating, preventing, ameliorating, controlling or reducing cerebrovascular or vascular disorders associated with CGRP receptor function.

Abstract: The disclosures herein relate to novel compounds of formula wherein R1, R2, R3 and R4 and n are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of inflammation, neurological or psychiatric disorders associated with modulating mGlu5 receptor function.

Abstract: A method of producing a conformational specific binding partner of a GPCR, the method comprising: a) providing a mutant GPCR of a parent GPCR, wherein the mutant GPCR has increased stability in a particular conformation relative to the parent GPCR; b) providing a test compound; c) determining whether the test compound binds to the mutant GPCR when residing in a particular conformation; and d) isolating a test compound that binds to the mutant GPCR when residing in the particular formation. Methods of producing GPCRs with increased stability relative to a parent GPCR are also disclosed.

Abstract: This invention relates to compounds that are agonists of the muscarinic M1 receptor and/or M4 receptor and which are useful in the treatment of muscarinic M1/M4 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds include those according to formula 1, or a salt thereof, wherein Q, R1, R2, R3 and R4 are as defined herein.