Abstract: Novel compounds, or pharmaceutically-acceptable salts, tautomers or prodrugs thereof, of Formula I wherein A, W, X, Z, R1-R3, and R8 are as defined in the specification, are provided. Also provided are methods of treating or preventing a melanin concentrating hormone-mediated disorder in a subject, comprising administering to a subject in need of such treatment or prevention a compound of Formula I.

Abstract: The instant invention provides for compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2) and PDK1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3 TYK2 and PDK1 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer.

Abstract: The present invention relates to a novel class of histone deacetylase inhibitors with aryl-pyrazolyl motifs. The compounds of this invention can be used to treat cancer. The compounds of this invention are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The present invention further provides pharmaceutical compositions comprising the compounds of this invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the compounds of this invention in vivo.

Abstract: The present invention relates to a novel class of aryl-fused spirocyclic compounds. These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases.

Abstract: The present invention relates to a novel class of substituted spirocyclic compounds, represented by the following structural Formula: I Wherein A, B and D are independently selected from CR12, NR1a, C(O) and O; E is selected from a bond, CR12, NR1a, C(O) and O; wherein at least one of A, B, D or E is CR12; and provided that when A is O, then E is not O; G is CR12; R is selected from NH2 and OH; These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing termin differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells.

Abstract: The present invention relates to a novel class of substituted spirocyclic compounds. These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases.

Abstract: Novel compounds, or pharmaceutically-acceptable salts, tautomers or prodrugs thereof, of Formula I wherein A, W, X, Z, R1-R3, and R8 are as defined in the specification, are provided. Also provided are methods of treating or preventing a melanin concentrating hormone-mediated disorder in a subject, comprising administering to a subject in need of such treatment or prevention a compound of Formula I.

Abstract: Novel compounds, or pharmaceutically-acceptable salts, tautomers or prodrugs thereof, of Formula I wherein A, W, X, Z, R1-R3, and R8 are as defined in the specification, are provided. Also provided are methods of treating or preventing a melanin concentrating hormone-mediated disorder in a subject, comprising administering to a subject in need of such treatment or prevention a compound of Formula I.

Abstract: The present invention relates to compounds of Formulas I and II, wherein B1, B2, B3, B4, C1, C2, ring D, L1, L2 and R1-4 are defined herein, synthetic intermediates, and pharmaceutical compositions, comprising such compounds. The compounds and compositions are capable of modulating various protein kinase receptors such as Tie-2 and Aurora and, therefore, influencing kinase related disease states and conditions. The compounds, for example, are capable of treating cancer caused by unregulated angiogenesis, and inflammation as well as other proliferative disorders.

Abstract: The present invention relates to a novel class of substituted spirocyclic compounds. These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases.

Abstract: The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation, cancer and related conditions. The compounds have a general Formula I wherein A1, A2, A3, B, R1, R2, R3 and R4 are defined herein. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of kinase mediated diseases using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention.

Abstract: The present invention relates to chemical compounds having a general formula I wherein A, B, D, E, G, H1-5 and R1-4 are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of these kinases. For example, the compounds are capable of modulating kinase enzymes thereby influencing the process of angiogenesis and treating angiogenesis-related diseases and other poliferative disorders, including cancer and inflammation. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of protein kinases.

Abstract: Novel compounds, or pharmaceutically-acceptable salts, tautomers or prodrugs thereof, of Formula I wherein W, X, Y, Z, R3-R6, and R11 are as defined in the specification, are provided. Also provided are methods of treating or preventing a melanin concentrating hormone-mediated disorder in a subject, comprising administering to a subject in need of such treatment or prevention a compound of Formula I.

Abstract: Novel compounds, or pharmaceutically-acceptable salts, tautomers or prodrugs thereof, of Formula I wherein A, W, X, Z, R1-R3, and R8 are as defined in the specification, are provided. Also provided are methods of treating or preventing a melanin concentrating hormone-mediated disorder in a subject, comprising administering to a subject in need of such treatment or prevention a compound of Formula I.