Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases; disorders and conditions.

Disclosed herein are secondary amine compounds that inhibit tRNA synthetase. The compounds of the invention are useful in inhibiting tRNA synthetase in Gram-negative bacteria and are useful in killing Gram-negative bacteria. The secondary amine compounds of the invention are also useful in the treatment of tuberculosis.

The specification generally relates to compounds of Formula (I), and pharmaceutically acceptable salts thereof, where A, U, V, W, X, Y, Z, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 have the meanings defined herein. Such compounds are modulators of RXFP1 and may be useful as therapeutic agents. The specification also relates to the use of such compounds to treat or prevent diseases and conditions including heart failure, heart failure with preserved ejection fraction, heart failure with mid-range ejection fraction, heart failure with reduced ejection fraction, chronic kidney disease and acute kidney injury. The specification further relates to compositions comprising such compounds, intermediates useful in processes for preparing such compounds, and processes for preparing such compounds using such intermediates.

Disclosed herein are compounds of formula (I) which are inhibitors of an IDO enzyme: (I). Also disclosed herein are uses of the compounds in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising these compounds. Further disclosed herein are uses of the compositions in the potential treatment or prevention of an IDO-associated disease or disorder. ##STR00001##

The application relates to a compound of Formula (I′) or (I): ##STR00001##
or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which modulates the activity of SSAO, a pharmaceutical composition comprising a compound of Formula (I′) or (I), and a method of treating or preventing a disease in which SSAO plays a role.

The present application is related to an improved process for synthesising 1-(difluoromethyl)-3-iodobicyclo[1.1.1]pentane from difluoromethyl iodide and [1.1.1]propellane. Difluoromethyl iodide is made by reacting an iodide salt with chlorodifluoroacetic acid in the presence of a solvent such as sulfolane and an inorganic base, [1.1.1]propellane is synthesised by reacting 1,1-dibromo-2,2-cis(chloromethyl)cyclopropane with a reagent such as magnesium, methyllithium or phenyllithium.

The present application provides a small-molecule inhibitor targeting an EB virus nuclear antigen protein, and/or a pharmaceutical composition containing the same, which can be used for the treatment of a disease caused by EBNA1 activity, such as, but not limited to, cancer, infectious mononucleosis, chronic fatigue syndrome, multiple sclerosis, systemic lupus erythematosus and/or rheumatoid arthritis. The present application further provides a small-molecule inhibitor targeting an EB virus nuclear antigen protein, and/or a pharmaceutical composition containing the same, which can be used for the treatment of a disease caused by EBV infection in a lytic and/or latent phase.

Provided is a compound according to Formula 1

##STR00001##

wherein X, R, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are as defined herein. The compound of Formula 1 can be useful in a composition and in a method for inducing ferroptosis in a cell.

The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of USP30, and the treatment of USP30-mediated disorders.

Disclosed herein are secondary amine compounds that inhibit tRNA synthetase. The compounds of the invention are useful in inhibiting tRNA synthetase in Gram-negative bacteria and are useful in killing Gram-negative bacteria. The secondary amine compounds of the invention are also useful in the treatment of tuberculosis.