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.

This invention relates to the new use of neurokinin-1(NK-1) receptor antagonists for treating sepsis, septic shock, systemic inflammatory response syndrome (SIRS), acute respiratory distress syndrome (ARDS) or multiple organ dysfunction syndrome (MODS). The invention further relates to pharmaceutical compositions comprising NK-1 receptor antagonists and combinations with one or more therapeutic agents, for such uses.

The present invention relates to compounds having dual pharmacological activity towards both the sigma (σ) receptor, and the μ-opiod receptor and more particularly to 1,9-diazaspiro undecane compounds having this pharmacological activity, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

The present invention relates to compounds having dual pharmacological activity towards both the sigma (σ) receptor, and the μ-opiod receptor and more particularly to 1,9-diazaspiro undecane compounds having this pharmacological activity, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

Compounds, compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo. Also disclosed are pharmaceutical compositions comprising a Cbl-b inhibitor and a cancer vaccine, as well as methods for treating cancer using a Cbl-b inhibitor and a cancer vaccine; and pharmaceutical compositions comprising a Cbl-b inhibitor and an oncolytic virus, as well as methods for treating cancer using a Cbl-b inhibitor and an oncolytic virus.

Compounds, compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo. Also disclosed are pharmaceutical compositions comprising a Cbl-b inhibitor and a cancer vaccine, as well as methods for treating cancer using a Cbl-b inhibitor and a cancer vaccine; and pharmaceutical compositions comprising a Cbl-b inhibitor and an oncolytic virus, as well as methods for treating cancer using a Cbl-b inhibitor and an oncolytic virus.

Novel spirocyclic compounds of formula I: and pharmaceutically acceptable salts thereof are disclosed as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. Pharmaceutical compositions and methods of treatment are also included. ##STR00001##

Novel spirocyclic compounds of formula I: and pharmaceutically acceptable salts thereof are disclosed as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. Pharmaceutical compositions and methods of treatment are also included. ##STR00001##

Provided are novel heteroaromatic compound as an Autotaxin inhibitor, a pharmaceutical composition comprising the compound, and a use thereof in a treatment of a disease with a pathological feature of Autotaxin overexpression in a mammal, wherein the compound is according to formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, tautomer, nitrogen oxide, metabolite, prodrug, or mixture thereof; wherein each of R.sup.1, Ar.sup.1, Ar.sup.2, Ar.sup.3, W, Y, Z, and Cy is defined in the present disclosure.

Provided are novel heteroaromatic compound as an Autotaxin inhibitor, a pharmaceutical composition comprising the compound, and a use thereof in a treatment of a disease with a pathological feature of Autotaxin overexpression in a mammal, wherein the compound is according to formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, tautomer, nitrogen oxide, metabolite, prodrug, or mixture thereof; wherein each of R.sup.1, Ar.sup.1, Ar.sup.2, Ar.sup.3, W, Y, Z, and Cy is defined in the present disclosure.