Abstract: A process for preparing and purifying a compound of Formula I is provided: thereof, wherein the subscript m is an integer of from 0 to 3; each Ra is independently selected from the group consisting of (C3-C8)cycloalkyl, (C1-C4)haloalkyl, halogen, —OH, —OR1, —SH, —SR1, —S(O)R1, —S(O)2R1, —SO2NH2, —C(O)NH2, —C(O)NHR1, —C(O)N(R1)2, —C(O)R1, —C(O)H, —CO2H, —CO2R1, —NO2, —NH2, —NHR1, —N(R1)2, wherein each R1 is independently (C1-C8)alkyl; L is a linking group selected from the group consisting of a bond or CH2; Qa, Qb, and Qc are each members independently selected from the group consisting of N, S, O and C(Rq) wherein each Rq is independently selected from the group consisting of H, C1-8 alkyl, halo and phenyl, and the ring having Qa, Qb, Qc and Y as ring vertices is a five-membered ring having two double bonds; and Y is selected from the group consisting of C and N.

Abstract: Pure crystalline forms of 1-benzyl-N-(4-carbamimidoylbenzyl)-1H-pyrazole-4-carboxamide acetate, and an amorphous form, pharmaceutical compositions thereof, and methods for making the same, are disclosed.

Abstract: Pure crystalline forms of 1-benzyl-N-(4-carbamimidoylbenzyl)-1H-pyrazole-4-carboxamide acetate, and an amorphous form, pharmaceutical compositions thereof, and methods for making the same, are disclosed.

Abstract: A process for preparing and purifying a compound of Formula I is provided: or a salt thereof, wherein the subscript m is an integer of from 0 to 3; each Ra is independently selected from the group consisting of (C3-C8)cycloalkyl, (C1-C4)haloalkyl, halogen, —OH, —OR1, —SH, —SR1, —S(O)R1, —S(O)2R1, —SO2NH2, —C(O)NH2, —C(O)NHR1, —C(O)N(R1)2, —C(O)R1, —C(O)H, —CO2R1, —NO2, —NH2, —NHR1, —N(R1)2, wherein each R1 is independently (C1-C8)alkyl; L is a linking group selected from the group consisting of a bond or CH2; Qa, Qb, and Qc are each members independently selected from the group consisting of N, S, O and C(Rq) wherein each Rq is independently selected from the group consisting of H, C1-8 alkyl, halo and phenyl, and the ring having Qa, Qb, Qc and Y as ring vertices is a five-membered ring having two double bonds; and Y is selected from the group consisting of C and N.

Abstract: A process for preparing and purifying a compound of Formula I is provided: or a salt thereof, wherein the subscript m is an integer of from 0 to 3; each Ra is independently selected from the group consisting of (C3-C8)cycloalkyl, (C1-C4)haloalkyl, halogen, —OH, —OR1, —SH, —SR1, —S(O)R1, —S(O)2R1, —SO2NH2, —C(O)NH2, —C(O)NHR1, —C(O)N(R1)2, —C(O)R1, —C(O)H, —CO2R1, —NO2, —NH2, —NHR1, —N(R1)2, wherein each R1 is independently (C1-C8)alkyl; L is a linking group selected from the group consisting of a bond or CH2; Qa, Qb, and Qc are each members independently selected from the group consisting of N, S, O and C(Rq) wherein each Rq is independently selected from the group consisting of H, C1-8 alkyl, halo and phenyl, and the ring having Qa, Qb, Qc and Y as ring vertices is a five-membered ring having two double bonds; and Y is selected from the group consisting of C and N.

Abstract: Pure crystalline forms of 1-benzyl-N-(4-carbamimidoylbenzyl)-1H-pyrazole-4-carboxamide acetate, and an amorphous form, pharmaceutical compositions thereof, and methods for making the same, are disclosed.

Abstract: The present invention provides prodrugs of compounds that inhibit the activity of plasma kallikrein (PK) and methods of preventing and treating plasma kallikrein dependent diseases or conditions, for example, diabetic macular edema, with the prodrugs having the formula:

Abstract: The present invention provides prodrugs of compounds that inhibit the activity of plasma kallikrein (PK) and methods of preventing and treating plasma kallikrein dependent diseases or conditions, for example, diabetic macular edema, with the prodrugs having the formula:

Abstract: This invention provides new pharmaceutically useful compounds that are prodrugs of inhibitors of plasma kallikrein and methods and compositions for preventing or treating plasma kallikrein dependent diseases or conditions, such as diabetic macular edema or hemorrhagic stroke, by administering prodrugs of the formula:

Abstract: We have identified classes of kallikrein inhibitors as compounds that are useful in the reduction of vascular permeability (e.g., retinal vascular permeability and cerebral vascular permeability) and astrocyte activation. Diseases and conditions associated with increased vascular permeability include diabetic retinopathy, hemorrhagic stroke, and macular edema. Diseases and conditions associated with astrocyte activation include Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, stroke, epilepsy, and brain trauma.

Abstract: The present invention provides prodrugs of compounds that inhibit the activity of plasma kallikrein (PK) and methods of preventing and treating plasma kallikrein dependent diseases or conditions, for example, diabetic macular edema, with the prodrugs having the formula:

Abstract: This invention provides new pharmaceutically useful compounds that are prodrugs of inhibitors of plasma kallikrein and methods and compositions for preventing or treating plasma kallikrein dependent diseases or conditions, such as diabetic macular edema or hemorrhagic stroke, by administering prodrugs of the formula:

Abstract: The present invention provides compounds that inhibit the activity of plasma kallikrein (PK) and methods of preventing and treating the formation of thrombin during or after a PK dependent disease or condition, for example, after fibrinolysis treatment.

Abstract: The present invention provides compounds that inhibit the activity of plasma kallikrein (PK) and methods of preventing and treating the formation of thrombin during or after a PK dependent disease or condition, for example, after fibrinolysis treatment.

Abstract: Disclosed are various forms of an active, isolated ?-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the brains of individuals afflicted with Alzheimer's disease. Recombinant cells that produce this enzyme either alone or in combination with some of its natural substrates (?-APPwt and ?-APPsw) are also disclosed, as are antibodies directed to such proteins. These compositions are useful for use in methods of selecting compounds that modulate ?-secretase. Inhibitors of ?-secretase are implicated as therapeutics in the treatment of neurodegenerative diseases, such as Alzheimer's disease.

Abstract: The present invention provides compounds that inhibit the activity of plasma kallikrein (PK) and methods of preventing and treating the formation of thrombin during or after a PK dependent disease or condition, for example, after fibrinolysis treatment.

Abstract: The present invention provides prodrugs of compounds that inhibit the activity of plasma kallikrein (PK) and methods of preventing and treating plasma kallikrein dependent diseases or conditions, for example, diabetic macular edema, with the prodrugs having the formula:

Abstract: We have identified classes of kallikrein inhibitors as compounds that are useful in the reduction of vascular permeability (e.g., retinal vascular permeability and cerebral vascular permeability) and astrocyte activation. Diseases and conditions associated with increased vascular permeability include diabetic retinopathy, hemorrhagic stroke, and macular edema. Diseases and conditions associated with astrocyte activation include Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, stroke, epilepsy, and brain trauma.

Abstract: The present invention provides compounds that inhibit the activity of plasma kallikrein (PK) and methods of preventing and treating the formation of thrombin during or after a PK dependent disease or condition, for example, after fibrinolysis treatment.

Abstract: Human BACE polypeptides having modifications to the N-linked glycosylation sites including one or more of the following amino acid substitutions: S174I, N223A, N153Q and N354S. DNA sequences, vectors, and host cells for producing the polypeptides. Crystalline protein compositions formed from the purified polypeptides. Methods of screening for compounds that inhibit A? using the polypeptides.