Abstract: This invention provides biphenyl derivatives of formula I: wherein R1, R2, R3, R4, R5, R6, R7, W, a, b and c are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The biphenyl derivatives of this invention possess both ?2 adrenergic receptor agonist and muscarinic receptor antagonist activity and therefore, such biphenyl derivatives are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.

Abstract: This invention provides biphenyl derivatives of formula I: wherein R1, R2, R3, R4, R5, R6, R7, W, a, b and c are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The biphenyl derivatives of this invention possess both ?2 adrenergic receptor agonist and muscarinic receptor antagonist activity and therefore, such biphenyl derivatives are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.

Abstract: This invention provides biphenyl derivatives of formula I: wherein R1, R2, R3, R4, R5, R6, R7, W, a, b and c are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The biphenyl derivatives of this invention possess both ?2 adrenergic receptor agonist and muscarinic receptor antagonist activity and therefore, such biphenyl derivatives are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.

Abstract: This invention provides biphenyl derivatives of formula I: 1

Abstract: The present invention provides methods and compositions for detection of compounds that have activity in modulating activity of membrane-spanning, signal-transducing (MSST) proteins, e.g., agonists, and antagonists. The detection method is based upon detection of a conformational change in a MSST protein upon interaction with a ligand. Conformational change of the MSST protein upon ligand interaction is accomplished by modifying the MSST protein to comprise a conformationally sensitive detectable probe, so that ligand interaction that results in a conformational change in the MSST protein is detected by a change in detectable signal from the detectable probe. The conformationally sensitive detectable probe can be a chemical label (e.g., a fluorophore) or moiety integral to the protein (e.g., a protease cleavage site, or immunodetectable moiety). The conformational assays of the invention provide for high-throughput screening.

Abstract: The present invention provides methods and compositions for detection of compounds that have activity in modulating G protein-coupled receptor (GPCR) activity, e.g., agonists, and antagonists. The detection method is based upon detection of a conformational change in a GPCR upon interaction with a ligand. Conformational change of the GPCR upon ligand interaction can be accomplished by modifying the GPCR to have a bound detectable label so that ligand interaction results in a conformational change in the GPCR that is detected by a change in detectable signal from the detectable label. Conformational change of the GPCR upon ligand interaction can also be detected by detecting a change in the accessibility of a protease cleavage site to protease cleavage, where the protease cleavage site is naturally-occurring in the GPCR or introduced into the GPCR.

Abstract: The present invention provides modified G protein &agr;-subunits which are characterized by constitutive localization to the plasma membrane; enhanced binding to one or more of the normal receptor binding partners for that &agr;-subunit; and efficient binding to and activation of G protein binding partners. The distribution of these modified &agr;-subunits, which are “tethered” to the plasma membrane, allows the regulation of receptor-G protein coupling, and thus G-protein signaling, in various biological systems.