Abstract: Covalent conjugates of an ?,?-disubstituted glycine ester and a modulator of the activity of a target intracellular enzyme or receptor, wherein the ester group of the conjugate is hydrolysable by one or more intracellular carboxylesterase enzymes to the corresponding acid and the ?,?-disubstituted glycine ester is conjugated to the modulator at a position remote from the binding interface between the inhibitor and the target enzyme or receptor pass into cells and the active acid hydrolysis product accumulates within the cells, as in the following compound:

Abstract: The present invention relates to a compound of Formula (I) having pharmacological activity, processes for its preparation, pharmaceutical compositions and their use in the treatment of certain parasitic certain parasitic protozoal infections such as malaria, in particular infection by Plasmodium falciparum. (S)—N-(2-fluoropyridin-4-yl)-3-methyl-2-(5-methyl-2,4-dioxo-1,2-dihydropyrido[3,4-d]pyrimidin-3(4H)-yl)butanamide.

Abstract: Disclosed are compounds having the formula: wherein X, Y, Z1, Z2, Z3, Z4, R5, RA, m, A. L, and B are as defined herein, and methods of making and using the same.

Abstract: Disclosed are compounds having the formula (Formula I)): wherein R1, R2, R3 and Z are as defined herein, and methods of making and using the same.

Abstract: Disclosed are compounds having the formula: wherein R1, R2, R3 and Z are as defined herein, and methods of making and using the same.

Abstract: Disclosed are compounds having the formula: wherein X is as defined herein, and methods of making and using the same.

Abstract: Disclosed are compounds having the formula: wherein X, Y, Z1, Z2, Z3, Z4, R5, RA, m, A, L, and B are as defined herein, and methods of making and using the same.

Abstract: A compound of formula (I): or a pharmaceutically acceptable salt thereof, compositions, combinations and medicaments containing said compounds and processes for their preparation.

Abstract: The present invention is directed to compounds and pharmaceutically acceptable salts thereof which are inhibitors of the activity or function of the phosphoinositide 3?OH kinase family (hereinafter PI3K) for use in the treatment or prevention of respiratory infections, the treatment of airway damage, and/or the prevention of airway injury in patients with a PI3K? mutation.

Abstract: The invention relates to activators of soluble guanylate cyclase and their use in pharmaceutical compositions, primarily topically administered ophthalmic compositions. The pharmaceutical compositions are useful for reducing intraocular pressure in animals of the mammalian species.

Abstract: This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung c

Abstract: The present invention relates to novel 3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one compounds that inhibit Lp-PLA2 activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases associated with the activity of Lp-PLA2, for example atherosclerosis, Alzheimer's disease.

Abstract: A system is provided that can include a processing device and a memory device in which instructions executable by the processing device are stored for causing the processing device to receive sensor data indicating a physiological characteristic of a patient. The instructions can also cause the processing device to electronically transform the sensor data into a risk score representative of a risk to the patient for a negative outcome by applying the physiological characteristic to at least one predictive model received from a predictive model database. The instructions can also cause the processing device to electronically determine a corrective option for reducing the risk by applying the physiological characteristic to a plurality of rules received from a rules database. The instructions can also cause the processing device to configure a display device to output a graphical user interface (GUI) comprising the risk score and the corrective option.

Abstract: Compounds of formula (I) inhibit HDAC activity: wherein A, B and D independently represent ?C— or ?N—; W is a divalent radical —CH?CH— or CH2CH2—; R1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular carboxyesterase enzymes to a carboxylic acid group; R2 is the side chain of a natural or non-natural alpha amino acid; z is 0 or 1; and Y, L1, and X1 are as defined in the claims.

Abstract: Disclosed are compounds having the formula: wherein R1, R2R3, R4 and R5 are as defined herein, and methods of making and using the same.

Abstract: Disclosed are 4-amino-2-butenamides of Formula (I) having pharmacological activity, pharmaceutical compositions containing them, and methods for the treatment of diseases mediated by the cathepsin C enzyme such as chronic obstructive pulmonary disease.

Abstract: This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung c

Abstract: The invention relates to improved variants of the anti-serum albumin immunoglobulin single variable domains, as well as ligands and drug conjugates comprising such variants, compositions, nucleic acids, vectors and hosts.

Abstract: Compounds of formula (I), and salts, N-oxides, hydrates and solvates thereof are histone deacetylase inhibitors and are useful in the treatment of cell proliferative diseases, including cancers: wherein Q, V and W independently represent —N? or —C?; B is a divalent radical selected from (B1), (B2), (B3), (B4), (B5) and (B6). wherein the bond marked * is linked to the ring containing Q, V and W through -[Linker1]- and the bond marked ** is linked to A through -[Linker2]-; A is an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system; -[Linker1]- and -[Linker2]- independently represent a bond, or a divalent linker radical; and R is (a) a radical of formula R1R2CHNH—Y-L1-X1—(CH2)z— or (b) a radical of formula R-L1-Y1—(CH2)z—.