Abstract: Heteroaryl sulfonyl compounds and compositions that have a KRAS Recognition Moiety bound to an electrophile for the selective covalent modification of KRAS, for example a mutant KRAS, to treat KRAS-mediated disorders are described.

Abstract: Heteroaryl sulfonyl compounds and compositions that have a CDK2 Recognition Moiety bound to an electrophile for the selective covalent modification of CDK2 to treat CDK2-mediated disorders are described.

Abstract: Disclosed herein are novel indazole-based compounds that inhibit fructokinase (aka ketohexokinase) and the downstream metabolic effects mediated by fructose metabolism. Fructokinase inhibitors specifically block the metabolism of both dietary and endogenous fructose metabolism and have a host of potential metabolic benefits. These benefits including blocking sugar craving and sugar induced metabolic syndrome and diabetes, but also blocking fructose metabolism can benefit the rare orphan disease Hereditary Fructose Intolerance, obesity, insulin resistance, metabolic syndrome, fatty liver, hypertension, cardiac injury from ischemia, certain cancers (including hepatocellular and pancreas), acute kidney injury from ischemia, heat stress, rhabdomyolysis or radiocontrast, and chronic diabetic and nondiabetic renal disease.

Abstract: Disclosed herein are novel indazole-based compounds that inhibit fructokinase (aka ketohexokinase) and the downstream metabolic effects mediated by fructose metabolism. Fructokinase inhibitors specifically block the metabolism of both dietary and endogenous fructose metabolism and have a host of potential metabolic benefits. These benefits including blocking sugar craving and sugar induced metabolic syndrome and diabetes, but also blocking fructose metabolism can benefit the rare orphan disease Hereditary Fructose Intolerance, obesity, insulin resistance, metabolic syndrome, fatty liver, hypertension, cardiac injury from ischemia, certain cancers (including hepatocellular and pancreas), acute kidney injury from ischemia, heat stress, rhabdomyolysis or radiocontrast, and chronic diabetic and nondiabetic renal disease.

Abstract: The present invention provides compounds of Formula (I) and pharmaceutical compositions comprising compounds of Formula I, and methods for using compounds of Formula I for treating or preventing thromboses, embolisms, hypercoaguability or fibrotic changes.

Abstract: The present invention provides a compound of Formula (I) wherein R1 is H or C1-6 alkyl, R2, is H or C1-6 alkyl or CH2OH, R3 is H or C1-6 alkyl, and R4 is H or C1-6 alkyl, provided that when R1, R2, and R3 are H, R4 is C1-6 alkyl, and when R1, R2, and R4 are H, then R3 is C1-6 alkyl, and when R1, R3, and R4 are H, R2 is C1-6 alkyl or —CH2OH, and when R2, R3, and R4 are H, then R1 is C1-6 alkyl; A is 1) a 9-10 membered bicyclic heterocycle having 1-3 heteroatoms independently selected from N, S and O, which 9-10 membered bicyclic heterocycle is unsubstituted or substituted with R5 and unsubstituted or substituted with R6 and unsubstituted or substituted with NH2, or 2) a 6-9 membered monocyclic or bicyclic carbocyclic ring system unsubstituted or substituted with R5, unsubstituted or substituted with R6, and unsubstituted or substituted with —CH2NH2; and B is 1) a 5- or 6-membered monocyclic heterocycle having 1 or 2 heteroatoms independently selected from N, S or O, which is unsubstituted or substitut

Abstract: The present invention provides a compound of Formula (I) where A is a heterocycle ring system and B is a heterocycle ring system or aryl ring system, and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes.

Abstract: The present invention provides a compound of Formula (I) where A is a heterocycle ring system and B is a heterocycle ring system or aryl ring system, and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes.

Abstract: The present invention provides a compound of Formula (I) wherein R1, R2, R3 and R4 are independently H or C1-6 alkyl, provided that when R1, R2, and R3 are H, R4 is C1-6 alkyl, and when R1, R2, and R4 are H, R3 is C1-6 alkyl, and when R1, R3, and R4 are H, R2 is C1-6 alkyl, and when R2, R3, and R4 are H, R is C1-6 alkyl; and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes.

Abstract: The present invention provides a compound of Formula (I) wherein R1 is H or C1-6 alkyl, R2, is H or C1-6 alkyl or CH2OH, R3 is H or C1-6 alkyl, and R4 is H or C1-6 alkyl, provided that when R1, R2, and R3 are H, R4 is C1-6 alkyl, and when R1, R2, and R4 are H, then R3 is C1-6 alkyl, and when R1, R3, and R4 are H, R2 is C1-6 alkyl or —CH2OH, and when R2, R3, and R4 are H, then R1 is C1-6 alkyl; A is 1) a 9-10 membered bicyclic heterocycle having 1-3 heteroatoms independently selected from N, S and O, which 9-10 membered bicyclic heterocycle is unsubstituted or substituted with R5 and unsubstituted or substituted with R6 and unsubstituted or substituted with NH2, or 2) a 6-9 membered monocyclic or bicyclic carbocyclic ring system unsubstituted or substituted with R5, unsubstituted or substituted with R6, and unsubstituted or substituted with —CH2NH2; and B is 1) a 5- or 6-membered monocyclic heterocycle having 1 or 2 heteroatoms independently selected from N, S or O, which is unsubstituted or substitut