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 substituted 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 present invention relates to a compound of formula (3Z,5S)-5-(hydroxymethyl)-1-[(2′-methyl-1,1′-biphenyl-4-yl)carbonyl]pyrrolidin-3-one O-meth19243yloxime, and/or an active metabolite thereof having antagonist action at the oxytocin receptor and/or vasopressin V1a receptor, to processes for their preparation, pharmaceutical compositions containing them and their use.

The present invention pertains to a composition comprising a calcium source, a TRP agonist, water and optionally an excipient, wherein the amount of the calcium source is at least 5 wt %, based on the total weight of the composition.

The present invention relates to a compound or a pharmacologically acceptable salt thereof having excellent tissue non-specific alkaline phosphatase inhibitory activity. The present invention provides a compound represented by the following formula (I): wherein X.sup.1 represents a nitrogen atom or CR.sup.9, R.sup.1 represents a hydrogen atom, a C.sup.1-C.sup.6 alkyl group, or a C.sup.1-C.sup.6 alkoxy group, R.sup.2 represents a halogen atom, R.sup.3 represents a hydrogen atom or a halogen atom, R.sup.4 represents a hydrogen atom or a halogen atom, and R5 represents a C.sup.1-C.sup.3 alkylsulfonyl group, a substituted C.sup.1-C.sup.6 alkyl group, a substituted C.sup.1-C.sup.6 haloalkyl group, a substituted C.sup.1-C.sup.6 alkoxy group, or a substituted C.sup.1-C.sup.6 alkylamino group, or a pharmacologically acceptable salt thereof.

##STR00001##

The present invention relates to a compound or a pharmacologically acceptable salt thereof having excellent tissue non-specific alkaline phosphatase inhibitory activity. The present invention provides a compound represented by the following formula (I): wherein X.sup.1 represents a nitrogen atom or CR.sup.9, R.sup.1 represents a hydrogen atom, a C.sup.1-C.sup.6 alkyl group, or a C.sup.1-C.sup.6 alkoxy group, R.sup.2 represents a halogen atom, R.sup.3 represents a hydrogen atom or a halogen atom, R.sup.4 represents a hydrogen atom or a halogen atom, and R5 represents a C.sup.1-C.sup.3 alkylsulfonyl group, a substituted C.sup.1-C.sup.6 alkyl group, a substituted C.sup.1-C.sup.6 haloalkyl group, a substituted C.sup.1-C.sup.6 alkoxy group, or a substituted C.sup.1-C.sup.6 alkylamino group, or a pharmacologically acceptable salt thereof.

##STR00001##

The present invention relates to stimulators and activators of soluble guanylate cyclase in combination with an inhibitor of neutral endopeptidase and/or angiotensin AII antagonists and the use thereof for the treatment and/or prophylaxis of cardiovascular disorders, for example heart failure with preserved ejection fraction or heart failure with reduced ejection fraction, renal disorders, for example chronic kidney failure, urological disorders, lung disorders, disorders of the central nervous system, for regulation of cerebral perfusion, for example in the event of vascular cerebral states of dementia, for the treatment and/or prophylaxis of fibrotic disorders and other disease symptoms (e.g. end organ damage affecting the brain, kidney or heart).

A parenteral nutrition including at least one of an amino acid, a dextrose, a lipid, an electrolyte or a mixture thereof and a trace element including at least one of zinc, copper, selenium, or manganese is provided. The parenteral nutrition including the trace element is stable for about at least 3 days to about 14 days. Methods of preparing and using the stable injectable parenteral nutrition are also provided.

A parenteral nutrition including at least one of an amino acid, a dextrose, a lipid, an electrolyte or a mixture thereof and a trace element including at least one of zinc, copper, selenium, or manganese is provided. The parenteral nutrition including the trace element is stable for about at least 3 days to about 14 days. Methods of preparing and using the stable injectable parenteral nutrition are also provided.

Expression of a phosphatase inhibitor in heart cells can be used to treat cardiac disorders, e.g., heart failure. Decreasing phosphatase activity can improve β-adrenergic responsiveness.

The present invention relates to stimulators and activators of soluble guanylate cyclase in combination with an inhibitor of neutral endopeptidase and/or angiotensin AII antagonists and the use thereof for the treatment and/or prophylaxis of cardiovascular disorders, for example heart failure with preserved ejection fraction or heart failure with reduced ejection fraction, renal disorders, for example chronic kidney failure, urological disorders, lung disorders, disorders of the central nervous system, for regulation of cerebral perfusion, for example in the event of vascular cerebral states of dementia, for the treatment and/or prophylaxis of fibrotic disorders and other disease symptoms (e.g. end organ damage affecting the brain, kidney or heart).