Compounds that activate a sphingosine-1-phosphate receptor of the subtype 1 are provided. Certain compounds selectively activate the receptor subtype 1 in relation to the sphingosine-1-phosphate receptor subtype 3. Uses and methods of inventive compounds for treatment of malconditions wherein activation, agonism, inhibition or antagonism of the S1P1 is medically indicated are provided.

Compounds that activate a sphingosine-1-phosphate receptor of the subtype 1 are provided. Certain compounds selectively activate the receptor subtype 1 in relation to the sphingosine-1-phosphate receptor subtype 3. Uses and methods of inventive compounds for treatment of malconditions wherein activation, agonism, inhibition or antagonism of the S1P1 is medically indicated are provided.

The present invention provides: a furoxan compound having a fluorine atom as a substituent group on the ring structure thereof; and a novel nitric oxide donor including the compound. The present invention relates to a fluorofuroxan compound represented by general formula (1) or (2). The compound of formula (1) can be manufactured by reacting a fluoride salt with a nitrofuroxan compound to substitute the nitro group with a fluoro group. The compound of formula (2) can be manufactured by subjecting the compounds of formula (1) to isomerization by irradiation with light.

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The present disclosure relates to bifunctional compounds, which find utility as modulators of α-synuclein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon. Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

The present disclosure relates to bifunctional compounds, which find utility as modulators of α-synuclein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon. Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

The present embodiments are directed, in part, to compounds, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof for modulating the activity of S.sub.1P.sub.1 receptor and methods of using the same.

The present embodiments are directed, in part, to compounds, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof for modulating the activity of S.sub.1P.sub.1 receptor and methods of using the same.

The present invention relates to a pharmaceutical combination comprising (i) firibastat, (ii) a diuretic and (iii) a blocker of the systemic renin-angiotensin system selected from the group consisting of angiotensin I converting enzyme inhibitors (ACEIs) and angiotensin II receptor type 1 (AT1R) antagonists. Said composition is particularly useful for the treatment of hypertension and related diseases and conditions.

The present invention relates to a pharmaceutical combination comprising (i) firibastat, (ii) a diuretic and (iii) a blocker of the systemic renin-angiotensin system selected from the group consisting of angiotensin I converting enzyme inhibitors (ACEIs) and angiotensin II receptor type 1 (AT1R) antagonists. Said composition is particularly useful for the treatment of hypertension and related diseases and conditions.

The present invention relates to a crystalline form of the compound (S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol.