The present invention provides an antitumor agent comprising a compound or a pharmaceutically acceptable salt thereof that covalently binds to GTP-bound KRASG12C as an active ingredient.

The present invention relates to certain compounds of formula (I) wherein—Ar is (Ar1) or (Ar2) and to their uses as antibacterial agents. The invention further relates to methods of treatment of bacterial infection with such compounds, optionally in combination with other antimicrobials and to compositions and pharmaceutical formulations containing such compounds. The invention additionally relates to coatings containing such compounds and to items having such coatings. ##STR00001##

The present invention relates to novel hydrazone derivatives in which a terminal amine group is substituted with an aryl group or a heteroaryl group, and uses thereof.

Methods are provided for modulating MRGPRX2 generally, or for treating a MRGPRX2 dependent condition more specifically, by contacting the MRGPRX2 or administering to a subject in need thereof, respectively, an effective amount of a compound having structure (I):

##STR00001##

or a pharmaceutically acceptable salt, isomer, hydrate, solvate or isotope thereof, wherein D, W, Z, R.sup.1, R.sup.2 and R.sup.3 are as defined herein. Pharmaceutical compositions containing such compounds, as well as the compounds themselves, are also provided.

Methods are provided for modulating MRGPRX2 generally, or for treating a MRGPRX2 dependent condition more specifically, by contacting the MRGPRX2 or administering to a subject in need thereof, respectively, an effective amount of a compound having structure (I):

##STR00001##

or a pharmaceutically acceptable salt, isomer, hydrate, solvate or isotope thereof, wherein D, W, Z, R.sup.1, R.sup.2 and R.sup.3 are as defined herein. Pharmaceutical compositions containing such compounds, as well as the compounds themselves, are also provided.

Provided are compounds that inhibit ferroptosis activity, or modulate or inhibit a disease associated with ferroptosis dysregulation, such as neuropathy, ischemia reperfusion injury, acute kidney failure and cancer, including corresponding sulfonamides, and pharmaceutically acceptable salts, hydrates and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition.

The invention relates to antibacterial compounds formula I

##STR00001##

wherein R.sup.1 is the group M, whereby M is one of the groups M.sup.A and M.sup.B represented below

##STR00002##

wherein A is a bond or C≡C; R.sup.1A is H or halogen; R.sup.2A is H or halogen; R.sup.3A is H, alkoxy, hydroxyalkoxy, hydroxyalkyl, dihydroxyalkyl, 2-hydroxyacetamido, substituted cycloprop-1-yl or substituted oxetan-3-yl; and R.sup.1B is hydroxyalkyl, dihydroxyalkyl, aminoalkyl, dialkylaminoalkyl, substituted cycloprop-1-yl, substituted cyclobutan-1-yl, substituted oxetan-3-yl, 3-hydroxythietan-3-yl, substituted azetidin-3-yl, trans-(cis-3,4-dihydroxy)-cyclopent-1-yl, 3-hydroxymethylbicyclo[1,1,1]pentan-1-yl, 4-hydroxytetrahydro-2H-pyran-4-yl, (3R,6S)-3-aminotetrahydro-2H-pyran-6-yl, piperidin-4-yl or 1-(2-hydroxyacetyppiperidin-4-yl;

and salts thereof.

A compound containing a benzene ring as shown in formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, an isotopic compound thereof, a crystal form thereof, a nitrogen oxide thereof, and a solvate thereof or a solvate of the pharmaceutically acceptable salt thereof are provided. The compound has high P2X4 antagonistic activity, good selectivity, low toxicity and good metabolic stability.

##STR00001##

The present invention provides compounds of Formula I,

##STR00001##

pharmaceutical compositions comprising these compounds and methods of using these compounds to treat or prevent a disease or disorder mediated as FXR modulators. Specifically, the present invention relates to isoxazole derivatives useful as agonists for FXR, and methods for their preparation and use.

The present invention provides compounds of Formula I,

##STR00001##

pharmaceutical compositions comprising these compounds and methods of using these compounds to treat or prevent a disease or disorder mediated as FXR modulators. Specifically, the present invention relates to isoxazole derivatives useful as agonists for FXR, and methods for their preparation and use.