The present invention relates the field of preservation of functional pancreatic islet and treatment of diabetes, particularly to the use of peptides comprising analogues, particularly retro-analogues of VDAC1-derived peptides, for treating diabetes.

The present invention relates the field of preservation of functional pancreatic islet and treatment of diabetes, particularly to the use of peptides comprising analogues, particularly retro-analogues of VDAC1-derived peptides, for treating diabetes.

An agent for preventing or ameliorating nocturia, containing rosmarinic acid or a salt thereof as an active ingredient.

An agent for preventing or ameliorating nocturia, containing rosmarinic acid or a salt thereof as an active ingredient.

A morphinan derivative represented by the following general formula (I): ##STR00001##
wherein R.sup.1 represents hydrogen, C.sub.1-10 alkyl, cycloalkylalkyl where the cycloalkyl moiety has 3 to 6 carbon atoms, and the alkylene moiety has 1 to 5 carbon atoms, etc.; R.sup.2 represents heterocyclic ring containing 1 to 4 heteroatoms selected from N, O and S and at least one carbon atom as ring-constituting atoms, containing at least one set of adjacent ring-constituting atoms bound by a double bond, and further substituted with at least one oxo group; Y binds to a carbon atom as a ring-constituting atom of R.sup.2; R.sup.3, R.sup.4, and R.sup.5 represent hydrogen, hydroxy, etc.; R.sup.6a and R.sup.6b represent hydrogen, etc.; R.sup.7 and R.sup.8 represent hydrogen, etc.; R.sup.9 and R.sup.10, which are the same or different, represent hydrogen, etc.; X represents O or CH.sub.2; and Y represents C(═O)); a tautomer or stereoisomer of the compound, or a pharmaceutically acceptable salt thereof, or a solvate thereof is used as an anxiolytic drug, antidepressant, etc.

A morphinan derivative represented by the following general formula (I): ##STR00001##
wherein R.sup.1 represents hydrogen, C.sub.1-10 alkyl, cycloalkylalkyl where the cycloalkyl moiety has 3 to 6 carbon atoms, and the alkylene moiety has 1 to 5 carbon atoms, etc.; R.sup.2 represents heterocyclic ring containing 1 to 4 heteroatoms selected from N, O and S and at least one carbon atom as ring-constituting atoms, containing at least one set of adjacent ring-constituting atoms bound by a double bond, and further substituted with at least one oxo group; Y binds to a carbon atom as a ring-constituting atom of R.sup.2; R.sup.3, R.sup.4, and R.sup.5 represent hydrogen, hydroxy, etc.; R.sup.6a and R.sup.6b represent hydrogen, etc.; R.sup.7 and R.sup.8 represent hydrogen, etc.; R.sup.9 and R.sup.10, which are the same or different, represent hydrogen, etc.; X represents O or CH.sub.2; and Y represents C(═O)); a tautomer or stereoisomer of the compound, or a pharmaceutically acceptable salt thereof, or a solvate thereof is used as an anxiolytic drug, antidepressant, etc.

The present invention relates to the finding that certain DPP-4 inhibitors are particularly suitable for treating and/or preventing metabolic diseases, particularly diabetes, in patients with insufficient glycemic control despite a therapy with an oral and/or a non-oral antidiabetic drug.

The problem to be solved by the present invention is to provide a compound suitable for a pharmaceutical composition, specifically an agent for treating nocturia.

The inventors have assumed that inhibition of nocturnal activity of placental leucine aminopeptidase (P-LAP), i.e. aminopeptidase that cleaves AVP, would maintain and/or increase an endogenous AVP level to enhance the antidiuretic effect, which would contribute to a decreased number of nocturnal voids, and have extensively studied compounds which inhibit P-LAP. As a result, the inventors have found that (2R)-3-amino-2-(pyridylmethyl)-2-hydroxy-propanoic acid derivatives have excellent P-LAP inhibitory activity. The inventors have evaluated antidiuretic effects in water-loaded rats and have found that the compounds increase endogenous AVP levels by inhibiting P-LAP and consequently reduce urine production. The present invention therefore provides compounds expected to be used as an agent for treating nocturia based on P-LAP inhibition.

The present invention relates to a substantially crystalline and free solid state form of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid (Form I), pharmaceutical compositions thereof, and methods of treatment therewith.

The present disclosure provides compounds that inhibit protein kinases, such as JAK, Axl, or Syk kinases, compositions comprising the compounds and methods of using the compounds to inhibit protein kinase and treat and/or prevent diseases associated with inappropriate kinase activity.