C07D215/54

QUINOLINE DERIVATIVES

The present disclosure provides a compound of Formula (I):

##STR00001##

or a pharmaceutically acceptable salt thereof as described herein. The present disclosure also provides pharmaceutical compositions comprising a compound of Formula (I), processes for preparing compounds of Formula (I), and therapeutic methods for treating inflammatory disease.

Analogues of hydroxychloroquine (HCQ) without retinal toxicity

The present invention relates to hydroxychloroquine analogues having an activity superior to that of hydroxychloroquine but free from retinal cytotoxicity of formula (I), their pharmaceutically acceptable salts, solvates or hydrates: ##STR00001##
their method of preparation and their use in the treatment of lupus erythematosus.

Analogues of hydroxychloroquine (HCQ) without retinal toxicity

The present invention relates to hydroxychloroquine analogues having an activity superior to that of hydroxychloroquine but free from retinal cytotoxicity of formula (I), their pharmaceutically acceptable salts, solvates or hydrates: ##STR00001##
their method of preparation and their use in the treatment of lupus erythematosus.

REMOVAL OF SENESCENCE-ASSOCIATED MACROPHAGES

In various aspects and embodiments provided are compounds, compositions and methods relating to aging, senescent cells (SCs) and/or senescence associate macrophages (SAMs). In certain aspects and embodiments provided are compounds and compositions that selectively kill or reprogram senescent cells (SCs) and or senescence associate macrophages (SAMs) and associated methods. In some embodiments, the compounds compositions and methods treat or reverse aging organism Normal tissue and/or age-related diseases.

REMOVAL OF SENESCENCE-ASSOCIATED MACROPHAGES

In various aspects and embodiments provided are compounds, compositions and methods relating to aging, senescent cells (SCs) and/or senescence associate macrophages (SAMs). In certain aspects and embodiments provided are compounds and compositions that selectively kill or reprogram senescent cells (SCs) and or senescence associate macrophages (SAMs) and associated methods. In some embodiments, the compounds compositions and methods treat or reverse aging organism Normal tissue and/or age-related diseases.

SUBSTITUTED QUINAZOLINES AS INHIBITORS OF KRAS G12C

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.

SUBSTITUTED QUINAZOLINES AS INHIBITORS OF KRAS G12C

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.

GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS AND METHODS RELATING THERETO

GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure:

##STR00001##

wherein R.sub.1a, R.sub.1b, R.sub.1c, R.sub.1d, R.sub.2, R.sub.2a, and A are as defined herein, including stereoisomers, esters, solvates and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS AND METHODS RELATING THERETO

GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure:

##STR00001##

wherein R.sub.1a, R.sub.1b, R.sub.1c, R.sub.1d, R.sub.2, R.sub.2a, and A are as defined herein, including stereoisomers, esters, solvates and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

Substituted quinazolines as inhibitors of KRAS G12C

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.