The present disclosure relates to 3-substituted 1,2,4-oxadiazole compounds and their derivatives, which are useful as T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) inhibitors or as dual inhibitors of TIM-3 and the programmed cell death 1 (PD-1) signaling pathway. The disclosure also relates to treatment of disorders by inhibiting an immunosuppressive signal induced by TIM-3, PD-1, PD-L1, and/or PD-L2.

The present disclosure relates generally to compositions and methods for inhibiting exon 3 skipping in the 6-pyruvoyltetrahydropterin synthase (PTS) gene in monocytes, monocyte-derived cells such as macrophages and dendritic cells of the precursor cells thereof. The inhibition can be achieved with genome editing of the genomic sequence to remove certain splicing factor recognition sites or inhibiting the expression or activity of the splicing factors that contribute to the cell-specific exon skipping. Monocytes and monocyte-derived cells that have reduced exon skipping in the PTS gene can generate more potent immune response and thus are useful in preventing or treating diseases such as infectious diseases and cancer.

The present invention provides compounds of Formula (I):

##STR00001##

wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are biased agonists, or β-Arrestin agonists of the angiotensin II receptor, which may be used as medicaments.

The present invention provides compounds of Formula (I):

##STR00001##

wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are biased agonists, or β-Arrestin agonists of the angiotensin II receptor, which may be used as medicaments.

The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5A inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5A activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

##STR00001##

The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5A inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5A activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

##STR00001##

The present invention is a method of treating or preventing Mycobacterium tuberculosis infection in a subject by administering to the subject an effective amount of oxazolidinone, specifically(N-(((S)-3-(dibenzo[b,e][1,4]dioxin-7-yl)-2-oxooxazolidin-5-yl)methyl)acetamide) or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

The present invention is a method of treating or preventing Mycobacterium tuberculosis infection in a subject by administering to the subject an effective amount of oxazolidinone, specifically(N-(((S)-3-(dibenzo[b,e][1,4]dioxin-7-yl)-2-oxooxazolidin-5-yl)methyl)acetamide) or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

The current invention is based on the determination that a S1P receptor modulator compound of formula (I):

##STR00001##

decreases the heart rate of a subject to which it is administered by about 5 beats/min or less daily, or about 4 beats/min or less daily, or about 3 beats/min or less daily, or about 2 beats/min or less daily, wherein the S1P receptor modulator is administered at an initial daily dosage which is substantially the same as the standard daily therapeutic dosage.

The current invention is based on the determination that a S1P receptor modulator compound of formula (I):

##STR00001##

decreases the heart rate of a subject to which it is administered by about 5 beats/min or less daily, or about 4 beats/min or less daily, or about 3 beats/min or less daily, or about 2 beats/min or less daily, wherein the S1P receptor modulator is administered at an initial daily dosage which is substantially the same as the standard daily therapeutic dosage.