Compounds of the formula II:

##STR00001## wherein R.sup.1 and R.sup.2 are independently H, F or CH.sub.3; or R.sup.1 forms an ethynyl bond and R.sup.2 is H or C.sub.3-C.sub.6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF.sub.3, OMe or halo; R.sup.3 is C.sub.1-C.sub.3 alkyl or C.sub.3-C.sub.6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R.sup.3 is C.sub.3-C.sub.6 cycloalkyl it may alternatively be gem subsituted with fluoro; R.sup.4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A.sub.1 is CH or N, A.sub.2 is CR.sup.6R7 or NR.sup.6, provided at least one of A.sub.1 and A.sub.2 comprises N; R.sup.6 is H, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.3 alkyl-O-C.sub.1-C.sub.3 alkyl, or when A.sub.2 is C, R.sup.6 can also be C.sub.1-C.sub.4 alkoxy or F; R.sup.7 is H, C.sub.1-C.sub.4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.

Compounds of the formula II:

##STR00001## wherein R.sup.1 and R.sup.2 are independently H, F or CH.sub.3; or R.sup.1 forms an ethynyl bond and R.sup.2 is H or C.sub.3-C.sub.6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF.sub.3, OMe or halo; R.sup.3 is C.sub.1-C.sub.3 alkyl or C.sub.3-C.sub.6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R.sup.3 is C.sub.3-C.sub.6 cycloalkyl it may alternatively be gem subsituted with fluoro; R.sup.4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A.sub.1 is CH or N, A.sub.2 is CR.sup.6R7 or NR.sup.6, provided at least one of A.sub.1 and A.sub.2 comprises N; R.sup.6 is H, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.3 alkyl-O-C.sub.1-C.sub.3 alkyl, or when A.sub.2 is C, R.sup.6 can also be C.sub.1-C.sub.4 alkoxy or F; R.sup.7 is H, C.sub.1-C.sub.4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.

The invention relates to a compound of formula (1):

A-B-D-E  (1) or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof, wherein: A is selected from monocyclic and bicyclic heteroaryl, which may independently substituted by alkyl or amino; B is selected from alkyl, heteroalkyl, alkyl-amino, aryl, heteroaryl, cycloalkyl, heterocyclyl and alkylene, wherein said groups may independently be substituted by alkyl; D is selected from aryl-amino, heteroaryl-amino, cycloalkyl-amino, heterocyclyl, heterocyclyl-amino, urea, thioamide, thiourea, sulfonamide, sulfoximine and sulfamoyl, wherein said aryl, heteroaryl, cycloalkyl and heterocyclyl groups may independently be substituted; and E is selected from aryl, heteroaryl, cycloalkyl, heterocyclyl, wherein said aryl, heteroaryl, cycloalkyl and heterocyclyl groups may independently be substituted.

The compounds of formula (1) are inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5). QC catalyzes the intramolecular cyclization of N-terminal glutamine residues into pyroglutamic acid (5-oxo-prolyl, pGlu*) under liberation of ammonia and the intramolecular cyclization of N-terminal glutamate residues into pyroglutamic acid under liberation of water.

The invention relates to a compound of formula (1):

A-B-D-E  (1) or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof, wherein: A is selected from monocyclic and bicyclic heteroaryl, which may independently substituted by alkyl or amino; B is selected from alkyl, heteroalkyl, alkyl-amino, aryl, heteroaryl, cycloalkyl, heterocyclyl and alkylene, wherein said groups may independently be substituted by alkyl; D is selected from aryl-amino, heteroaryl-amino, cycloalkyl-amino, heterocyclyl, heterocyclyl-amino, urea, thioamide, thiourea, sulfonamide, sulfoximine and sulfamoyl, wherein said aryl, heteroaryl, cycloalkyl and heterocyclyl groups may independently be substituted; and E is selected from aryl, heteroaryl, cycloalkyl, heterocyclyl, wherein said aryl, heteroaryl, cycloalkyl and heterocyclyl groups may independently be substituted.

The compounds of formula (1) are inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5). QC catalyzes the intramolecular cyclization of N-terminal glutamine residues into pyroglutamic acid (5-oxo-prolyl, pGlu*) under liberation of ammonia and the intramolecular cyclization of N-terminal glutamate residues into pyroglutamic acid under liberation of water.

Compounds that inhibit HIF-2α, and compositions containing the compound(s) and methods for synthesizing the compounds, are described herein. Also described are the use of such compounds and compositions for the treatment of a diverse array of diseases, disorders, and conditions, including cancer- and immune-related disorders that are mediated, at least in part, by HIF-2α.

The invention provides small molecule heteroaromatic compounds that are ATP-competitive tyrosine kinase inhibitors displaying a significant inhibitory potency towards resistant T315I ABL mutants. The compounds of the invention find a useful application in the treatment of BCR-ABL inhibitor resistant diseases, such as imatinib resistant chronic myelogenous leukemia.

The invention provides small molecule heteroaromatic compounds that are ATP-competitive tyrosine kinase inhibitors displaying a significant inhibitory potency towards resistant T315I ABL mutants. The compounds of the invention find a useful application in the treatment of BCR-ABL inhibitor resistant diseases, such as imatinib resistant chronic myelogenous leukemia.

There is herein provided a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein the ring containing Q.sup.1 to Q.sup.5, and the groups R.sup.1, R.sup.2 and R.sup.3, have meanings as provided in the description. ##STR00001##

Compounds that inhibit HIF-2α, and compositions containing the compound(s) and methods for synthesizing the compounds, are described herein. Also described are the use of such compounds and compositions for the treatment of a diverse array of diseases, disorders, and conditions, including cancer- and immune-related disorders that are mediated, at least in part, by HIF-2α.

The present invention provides a method for obtaining a specifically-shaped crystal (specifically, spherocrystal) of a compound with good reproducibility. This method for producing a specifically-shaped crystal (specifically spherocrystal) of a compound comprises: (1) a step for preparing a supersaturated solution of a compound having a degree of supersaturation equal to or higher than a critical degree of supersaturation; and (2) a step for precipitating a specifically-shaped crystal (specifically spherocrystal) of a compound from the supersaturated solution.