An application of a substituted crotonamide, in particular being an application of (E)-N-(3-cyano-7-ethoxyl-4-(3-ethynylphenylamino)quinoline-6-yl)-4-(dimethylamino)but-2-enamide and a pharmaceutically acceptable salt and solvate thereof in the preparation of a drug for treating cancer mediated by a rare EGFR mutation.

The present disclosure relates generally to inhibitors of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), compositions thereof, and methods of using said compounds and compositions thereof. More specifically, the present disclosure relates to sulfoximine-based inhibitors of ENPP1 and methods of their use for treating disease mediated by ENPP1.

The present disclosure provides tetrahydroquinoline derivatives of Formula (I)

##STR00001##

wherein X.sub.1 and X.sub.2 each, independently, are oxygen or sulphur; R.sub.1 is a lower alkoxy, or an optionally substituted aryl group; R.sub.2 is selected from a group consisting of hydrogen, lower alkyl, haloalkyl, or an amino group; R.sub.3 and R.sub.4 each, independently, are hydrogen, or lower alkyl groups; and R5 and R6 are optionally substituted aryl groups. The present disclosure also provides a method for making the compound of Formula (I).

The present disclosure provides tetrahydroquinoline derivatives of Formula (I)

##STR00001##

wherein X.sub.1 and X.sub.2 each, independently, are oxygen or sulphur; R.sub.1 is a lower alkoxy, or an optionally substituted aryl group; R.sub.2 is selected from a group consisting of hydrogen, lower alkyl, haloalkyl, or an amino group; R.sub.3 and R.sub.4 each, independently, are hydrogen, or lower alkyl groups; and R5 and R6 are optionally substituted aryl groups. The present disclosure also provides a method for making the compound of Formula (I).

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I):

##STR00001##

or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R.sup.1, R.sup.2a, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, G.sup.1, G.sup.2, L.sup.1, L.sup.2, m.sup.1, m.sup.2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I):

##STR00001##

or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R.sup.1, R.sup.2a, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, G.sup.1, G.sup.2, L.sup.1, L.sup.2, m.sup.1, m.sup.2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

The present disclosure is directed to formulations of novel quinolines and their pharmaceutically acceptable salts, which are useful for the treatment of protein kinases mediated diseases and conditions. The compounds of this disclosure have a general Formula I

##STR00001## wherein R.sup.10 to R.sup.14 and X are defined herein.

The present disclosure is directed to formulations of novel quinolines and their pharmaceutically acceptable salts, which are useful for the treatment of protein kinases mediated diseases and conditions. The compounds of this disclosure have a general Formula I

##STR00001## wherein R.sup.10 to R.sup.14 and X are defined herein.

The present invention covers new quinoline compounds of general formula (I): ##STR00001##
in which A, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, and Q are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment, control and/or prevention of diseases, in particular of helminth infections, as a sole agent or in combination with other active ingredients.

The present invention relates to a new process for preparing quinoline compounds of the general formula (II): in which Q, A, R4, R.sup.3 and R.sup.3′, are as defined herein, as well as to the intermediate compounds of said new process. ##STR00001##