Abstract: The x-ray crystal structure of BACE or BACE-like proteins is useful for solving the structure of other molecules or molecular complexes, and identifying and/or designing potential modifiers of BACE activity.

Abstract: Compounds of formula (I): wherein the substituents are as defined herein, and their salt, solvates, and prodrugs are procollagen C-proteinase (PCP) inhibitors useful in treating conditions mediated by PCP.

Abstract: The present invention relates to novel to P2X7 inhibitors of formula I and to processes for their preparation, intermediates useful in their preparation, pharmaceutical compositions containing them, and their use in therapy. The active compounds of the present invention are potent inhibitors of P2X7 and as such are useful in the treatment of inflammation, osteoarthritis, rheumatoid arthritis, cancer, reperfusion or ischemia in stroke or heart attack, autoimmune diseases and other disorders.

Abstract: This invention provides a compound of the formula (I): wherein R1 represents a (C1–C6)alkyl group; R2 represents a hydrogen atom, a halogen atom, a hydroxy group, a (C1–C6)alkyl group or a (C1–C6)alkoxy group; R3, R4, R5 and R6 each independently represents a hydrogen atom, a (C1–C6)alkyl, or a halogen atom; R7 represents a hydrogen atom, a halogen atom, a hydroxy group, a (C1–C6)alkyl group optionally substituted with a piperidino group, a (C1–C6)alkoxy group optionally substituted with a 3–7 membered cycloalkyl ring, a hydroxy(C1–C6)alkoxy group, a (C1–C6)alkoxy-(C1–C6)alkyl group, a (C1–C6)alkoxy-(C1–C6)alkoxy group, a halo (C1–C6)alkyl group, a (C1–C6)alkylthio group, a (C1–C6)alkylsulfinyl group or a (C1–C6)alkylsulfonyl group; R8 represents a (C1–C6)alkyl group, a halo(C1–C6)alkyl group, a (C1–C6)alkoxy group, a hydroxy(C1–C6)alkoxy group, a (C1–C6)alkoxy-(C1–C6)alkyl group or a (C1–C6)alkoxy-(C1–C6)alkoxy group; or R7 and R8, when adjacent to each other, taken together with the carbon atoms to whic

Abstract: There is disclosed a method and apparatus for an object locator system (10) for requesting and obtaining information about the location of a mobile object, having attached thereon a lightweight object locator (42), operable in a region served by a two-way paging system (12) and a global positioning satellite system (50). The object locator (42) may be selectively activated to conserve power or enabled to respond only when beyond or within a boundary. Further, the object locator system (10) may provide the location information in several forms including rectangular or polar coordinates referred to a base station (18) or origin, position on a map display, etc.

Abstract: The present invention relates to a compound of the formula 1 wherein A and Ar are as defined herein. Such novel pyrimidine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.

Abstract: Novel imidazole compounds, including derivatives thereof, to intermediates for their preparation, to pharmaceutical compositions containing them and to their medicinal use are described. The compounds of the present invention are potent inhibitors of transforming growth factor (“TGF”)- signaling pathway. They are useful in the treatment of various TGF-related disease states including, for example, cancer and fibrotic diseases.

Abstract: This invention is directed to compounds of the formula (I): and their pharmaceutically acceptable salts, wherein R1, R2, and R3 are as defined herein; intermediates for the synthesis of such compounds, pharmaceutical compositions containing such compounds; and methods of using such compounds in the treatment of neurological and psychological disorders.

Abstract: The present invention provides compounds of formula (I) the prodrugs thereof, and the pharmaceutically acceptable salts of the compounds and prodrugs, wherein Ra, Rb, R1, and R2 are as defined herein; pharmaceutical compositions thereof; and uses thereof.

Abstract: The present invention relates to a semi-solid filling medium which comprises a camptothecin derivative; a pharmaceutically acceptable carrier matrix which is a polyglycolized glyceride; and an effective thickening-reducing and stabilizing-promoting amount of one or more pharmaceutically acceptable excipients.

Abstract: A polyketide synthase (“PKS”) of Type I is a complex multienzyme including a loading domain linked to a multiplicity of extension domains. The first extension module receives an acyl starter unit from the loading domain and each extension module adds a further ketide unit which may undergo processing (e.g. reduction). We have found that the Ksq domain possessed by some PKS's has decarboxylating activity, e.g. generating (substituted) acyl from (substituted) malonyl. The CLF domain of type II PKS's has similar activity. By inserting loading modules including such domains into PKS's not normally possessing them it is possible to control the starter units used.

Abstract: PPAR alpha activators, pharmaceutical compositions containing such compounds and the use of such compounds to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases, in mammals, including humans.

Abstract: Novel pyrazine compounds, including derivatives thereof, to intermediates for their preparation, to pharmaceutical compositions containing them and to their medicinal use are described. The compounds of the present invention are potent inhibitors of transforming growth factor (“TGF”)-? signaling pathway. They are useful in the treatment of various TGF-related disease states including, for example, cancer and fibrotic diseases.

Abstract: The invention relates to trycyclic lactam indole derivatives and triacyclic lactam benzimodole derivatives and their use in inhibiting the activity of PARP enzyme. The invention also relates to the use of these compounds in the preparation of medicaments.

Abstract: The present invention relates to antibodies including human antibodies and antigen-binding portions thereof that bind to the extracellular domain (ECD) of activin receptor-like kinase-1 (ALK-1) and that function to abrogate the ALK-1/TGF-beta-1/Smad1 signaling pathway. The invention also relates to heavy and light chain immunoglobulins derived from human anti-ALK-1 antibodies and nucleic acid molecules encoding such immunoglobulins. The present invention also relates to methods of making human anti-ALK-1 antibodies, compositions comprising these antibodies and methods of using the antibodies and compositions. The invention also relates to transgenic animals or plants comprising nucleic acid molecules of the present invention.

Abstract: The invention provides a process for the preparation of a compound of the formula: or an acid addition or base salt thereof, wherein R is phenyl optionally substituted by 1 to 3 substituents each independently selected from halo and trifluoromethyl; R1 is C1–C6 alkyl; and “Het” is pyrimidinyl optionally substituted by 1 to 3 substituents each independently selected from C1–C4 alkyl, C1–C4 alkoxy, halo, oxo, benzyl and benzyloxy, comprising reaction of a compound of the formula: wherein R is as previously defined for a compound of the formula (I), with a compound of the formula: wherein R1 and “Het” are as previously defined for a compound of the formula (I) and X is chloro, bromo or iodo, in the presence of zinc, iodine and/or a Lewis acid and an aprotic organic solvent: said process being optionally followed by conversion of the compound of the formula (I) to an acid addition or base salt thereof.

Abstract: This invention is directed to EP4 receptor selective prostaglandin agonists of the Formula I, wherein R2, X, Z and Q are as defined in the specification. This invention is also directed to pharmaceutical compositions containing those compounds. This invention is also directed to methods of treating conditions which present with low bone mass, particularly osteoporosis, frailty, an osteoporotic fracture, a bone defect, childhood idiopathic bone loss, alveolar bone loss, mandibular bone loss, bone fracture, osteotomy, bone loss associated with periodontitis, or prosthetic ingrowth in a mammal comprising administering those compounds.

Abstract: A compound of the formula wherein R1, R2 and R3 are as defined above, useful as inhibitors of protein kinases, such as the enzyme Janus Kinase 3.

Abstract: The present invention relates to processes for the preparation of any of the intermediate 1,3-substituted indenes of the formulae (Ia), (Ib) and (Ic) or a mixture thereof: wherein R1, R2, R3, R4, and R5 are defined herein. Compounds of formulae (Ia), (Ib) and (Ic) or mixtures thereof are useful in the preparation of compounds of formula (II): wherein R2, R3 and R6 are also defined herein.

Abstract: Compounds of this formula are useful for treating or preventing, obesity, breast cancer, osteoporosis, endometriosis, cardiovascular disease and prostatic disease.