Abstract: New pyrimidine or pyridine based compounds, compositions and methods of inhibiting the activity of glycogen synthase kinase (GSK3) in vitro and of treatment of GSK3 mediated disorders in vivo are provided. The methods, compounds and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents in the treatment of disorders mediated by GSK3 activity, such as in the treatment of diabetes, Alzheimer's disease and other neurodegenerative disorders, obesity, atherosclerotic cardiovascular disease, essential hypertension, polycystic ovary syndrome, syndrome X, ischemia, traumatic brain injury, bipolar disorder, immunodeficiency or cancer.

Abstract: New pyrimidine or pyridine based compounds, compositions and methods of inhibiting the activity of glycogen synthase kinase (GSK3) in vitro and of treatment of GSK3 mediated disorders in vivo are provided. The methods, compounds and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents in the treatment of disorders mediated by GSK3 activity, such as diabetes, Alzheimer's disease and other neurodegenerative disorders, obesity, atherosclerotic cardiovascular disease, essential hypertension, polycystic ovary syndrome, syndrome X, ischemia, traumatic brain injury, bipolar disorder, immunodeficiency or cancer.

Abstract: The invention provides truncated GSK3 polypeptides capable of crystallization, including GSK3&agr; and GSK3&bgr; polypeptides, and use of these polypeptides to identify and optimize GSK3 inhibitors. Also provided are GSK3 polypeptides having at least one substituted amino acid that differs from wild-type GSK3, wherein the substituted amino acid is incapable of being phosphorylated. The invention finds use in providing methods of identifying and optimizing compounds useful for treating diseases mediated by GSK3 activity, including Alzheimer's disease, type 2 diabetes, and inflammation.

Abstract: Novel pyridine and pyrimidine derivatives which selectively inhibit glycogen synthase kinase 3 are provided and methods of preparing these compounds are provided. These compounds are useful in treating certain conditions which may be mediated by glycogen synthase kinase 3.

Abstract: The invention provides truncated GSK3 polypeptides capable of crystallization, including GSK3&agr; and GSK3&bgr; polypeptides, and use of these polypeptides to identify and optimize GSK3 inhibitors. Also provided are GSK3 polypeptides having at least one substituted amino acid that differs from wild-type GSK3, wherein the substituted amino acid is incapable of being phosphorylated. The invention finds use in providing methods of identifying and optimizing compounds useful for treating diseases mediated by GSK3 activity, including Alzheimer's disease, type 2 diabetes, and inflammation.

Abstract: Compounds of formula 1: ##STR1## wherein R.sub.1 is alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl, substituted with 0-3 substituents selected from lower alkyl, halo, hydroxy, lower alkoxy, amino, lower alkyl-amino, and nitro;R.sub.2 is hydroxy, amino, or lower alkoxy;R.sub.3 is H, lower alkyl, lower acyl, lower alkoxy-acyl, or amnino-acyl;R.sub.4 is H or lower alkyl; and pharmaceutically acceptable salts and esters thereof; are effective inhibitors of GSK3.

Abstract: The invention provides for use of selective inhibitors of GSK3 for treatment of diseases that are mediated by GSK3 activity, including non-insulin dependent diabetes mellitus (NIDDM) and Alzheimer's disease. Also described are methods of identifying inhibitors of GSK3 activity. The selective GSK3 inhibitor can be a peptide, peptoid, small organic molecule, or polynucleotide.

Abstract: The invention provides for use of selective inhibitors of GSK3 for treatment of diseases that are mediated by GSK3 activity, including non-insulin dependent diabetes mellitus (NIDDM) and Alzheimer's disease. Also described are methods of identifying inhibitors of GSK3 activity. The selective GSK3 inhibitor can be a peptide, peptoid, small organic molecule, or polynucleotide.

Abstract: A method and apparatus for determining with high resolution the fidelity of communications over a communications channel is disclosed. Portable/mobile radios freely roaming between multiple trunked RF communications sites calculate the fidelity of communications received over current and alternate channels with comprehensive, high bit error resolution using a weighted average error dispersion procedure. The weighted average error dispersion analysis generates for each group of redundant messages (and in some instances subpreamble bits) received by a roaming radio in each message frame a weighted average error dispersion number whose incrementally increasing magnitude reflects deteriorating signal fidelity. Decisions about switching to alternate communications channels are made by the roaming radio based on the incrementally changing weighted error dispersion number so that communication channels may be selected to achieve optimum signal fidelity and continuity of communication.

Abstract: Digitally trunked radio transceivers are permitted to roam over an extended coverage area including two or more digitally trunked radio frequency communication networks. Each network includes at least one digital repeater site having a corresponding site coverage area and serving digitally trunked radio transceivers disposed within or near the site coverage area. Each network also includes a local multisite switch for routing communications between the digital repeater sites within the networks. Site adjacency information is established for each site and communicated between the networks. Each digitally trunked transceiver maintains a site adjacency list for its currently selected site and modifies that list when the transceiver roams into a new site coverage area and selects a new repeater site.