Abstract: The disclosure provides FOXO1 inhibitors having beneficial properties such as selectivity and metabolic stability. FOXO1 inhibitors are useful in the treatment of diabetes.

Abstract: The present disclosure relates to 1,4-benzothiazepine derivatives and use thereof to treat conditions associated with ryanodine receptors that regulate calcium channel functioning in cells.

Abstract: The present disclosure relates to crystalline forms of the compound 4-[(7-methoxy-2,3-dihydro-1,4-benzothiazepin-4(5H)yl)methyl]benzoic acid hemifumarate, pharmaceutical compositions comprising these compounds and uses thereof to treat diseases and conditions associated with Ryanodine Receptor (RyR) dysfunction, in particular cardiac and musculoskeletal disorders and diseases.

Abstract: The present disclosure relates to crystalline forms of the compound 4-[(7-methoxy-2,3-dihydro-1, 4-benzothiazepin-4(5H)yl)methyl]benzoic acid hemifumarate, pharmaceutical compositions comprising these compounds and uses thereof to treat diseases and conditions associated with Ryanodine Receptor (RyR) dysfunction, in particular cardiac and musculoskeletal disorders and diseases.

Abstract: The present disclosure relates to crystalline forms of the compound 4-[(7-methoxy-2,3-dihydro-1,4-benzothiazepin-4(5H)yl)methyl]benzoic acid hemifumarate, pharmaceutical compositions comprising these compounds and uses thereof to treat diseases and conditions associated with Ryanodine Receptor (RyR) dysfunction, in particular cardiac and musculoskeletal disorders and diseases.

Abstract: The present disclosure relates to crystalline forms of the compound 4-[(7-methoxy-2,3-dihydro-1,4-benzothiazepin-4(5H)yl)methyl]benzoic acid hemifumarate, pharmaceutical compositions comprising these compounds and uses thereof to treat diseases and conditions associated with Ryanodine Receptor (RyR) dysfunction, in particular cardiac and musculoskeletal disorders and diseases.

Abstract: Various embodiments relate to a compound (represented by Formula I) or a pharmaceutically acceptable salt or tautomer thereof. The compound may selectively inhibit a Forkhead Box O1 (FOXO1) transcription factor. Various embodiments relate to methods comprising administering to a mammal having a disease or disorder associated with impaired pancreatic endocrine function, a therapeutically effective amount of the compound or a pharmaceutically acceptable salt or tautomer thereof. Various embodiments relate to methods for producing enteroendocrine cells that make and secrete insulin in a mammal, comprising administering to the mammal an effective amount of the compound or a pharmaceutically acceptable salt or tautomer thereof.

Abstract: The invention provides a process for preparing a 2,3,4,5-tetrahydro[1,4]benzothiazepine of formula: by reacting a [2-(acylaminoethyl)thio]arene of formula with an aldehyde or a multimer thereof, and with an acid. The invention also provides for first reacting the [2-(acylaminoethyl)thio]arene with the aldehyde or multimer thereof and a base to form an [N-hydroxymethyl-2-[acylaminoethyl)thio]arene of formula then treating the [N-hydroxymethyl-2-(acylaminoethyl)thio]arene with the acid to form the 2,3,4,5-tetrahydro[1,4]benzothiazepine.

Abstract: The present invention relates to 1,4-benzothiazepine derivatives and their use to treat conditions, disorders and diseases associated with ryanodine receptors (RyRs) that regulate calcium channel functioning in cells. The invention also discloses pharmaceutical compositions comprising the compounds and uses thereof to treat diseases and conditions associated with RyRs, in particular cardiac, musculoskeletal and central nervous system (CNS) disorders.

Abstract: The present invention relates to 1,4-benzothiazepine derivatives and their use to treat conditions, disorders and diseases associated with ryanodine receptors (RyRs) that regulate calcium channel functioning in cells. The invention also discloses pharmaceutical compositions comprising the compounds and uses thereof to treat diseases and conditions associated with RyRs, in particular cardiac, musculoskeletal and central nervous system (CNS) disorders.

Abstract: The invention provides a process for preparing a 2,3,4,5-tetrahydro[1.4]benzothiazepine of formula: by reacting a [2-(acylaminoethyl)thio]arene of formula with an aldehyde or a multimer thereof, and with an acid. The invention also provides for first reacting the [2-(acylaminoethyl)thio]arene with the aldehyde or multimer thereof and a base to form an [N-hydroxymethyl-2-[acylaminoethyl)thio]arene of formula then treating the [N-hydroxymethyl-2-(acylaminoethyl)thio]arene with the acid to form the 2,3,4,5-tetrahydro[1,4]benzothiazepine.

Abstract: The present invention relates to 1,4-benzothiazepine derivatives and their use to treat conditions, disorders and diseases associated with ryanodine receptors (RyRs) that regulate calcium channel functioning in cells. The invention also discloses pharmaceutical compositions comprising the compounds and uses thereof to treat diseases and conditions associated with RyRs, in particular cardiac, musculoskeletal and central nervous system (CNS) disorders.

Abstract: The invention provides a process for preparing a 2,3,4,5-tetrahydro[1,4]benzothiazepine of formula: by reacting a [2-(acylaminoethyl)thio]arene of formula with an aldehyde or a multimer thereof, and with an acid. The invention also provides for first reacting the [2-(acylaminoethyl)thio]arene with the aldehyde or multimer thereof and a base to form an [N-hydroxymethyl-2-[acylaminoethyl)thio]arene of formula then treating the [N-hydroxymethyl-2-(acylaminoethyl)thio]arene with the acid to form the 2,3,4,5-tetrahydro[1,4]benzothiazepine.

Abstract: The present invention relates to 1,4-benzothiazepine derivatives and their use to treat conditions, disorders and diseases associated with ryanodine receptors (RyRs) that regulate calcium channel functioning in cells. The invention also discloses pharmaceutical compositions comprising the compounds and uses thereof to treat diseases and conditions associated with RyRs, in particular cardiac, musculoskeletal and central nervous system (CNS) disorders.

Abstract: The present invention is directed to prodrugs of hydroxamic acid based histone deacetylase (HDAC) inhibitors, e.g., suberoylanilide hydroxamic acid (SAHA). The prodrugs are acylated derivatives having increased aqueous solubility and cellular permeability as compared with the free hydroxamic acid, and are useful for inhibiting HDACs, and for selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the prodrugs of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The prodrugs of the invention are also useful in the prevention and treatment of thioredoxin (TRX)-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases.

Abstract: This invention relates to imidazopyrazine substituted piperidine derivatives and their use as pharmaceuticals.

Abstract: A method of treatment of anxiety disorders which comprises administering to a host in need thereof an effective amount of a compound of formula (I):

Abstract: This invention relates to imidazopyrimidine substituted piperidine derivatives and their use as pharmaceuticals.

Abstract: This invention relates to imidazopyrazine substituted piperidine derivatives and their use as pharmaceuticals.

Abstract: A method of treatment of anxiety disorders which comprises administering to a host in need thereof an effective amount of a compound of formula (I):