The present disclosure provides GLP-1R agonists, and compositions, methods, and kits thereof. Such compounds are generally useful for treating a GLP-1R mediated disease or condition in a human.

The present disclosure relates generally to compounds that bind to Lysophosphatidic Acid Receptor 1 (LPAR1) and act as antagonists of LPAR1. The disclosure further relates to the use of the compounds for the preparation of a medicament for the treatment of diseases and/or conditions through binding of LPAR1, including fibrosis and liver diseases such as non alcoholic steatohepatitis (NASH).

The present disclosure relates generally to compounds that bind to Lysophosphatidic Acid Receptor 1 (LPAR1) and act as antagonists of LPAR1. The disclosure further relates to the use of the compounds for the preparation of a medicament for the treatment of diseases and/or conditions through binding of LPAR1, including fibrosis and liver diseases such as non alcoholic steatohepatitis (NASH).

The present application is directed to compounds of Formula I:

##STR00001##

compounds comprising these compounds and their uses, for example as medicaments for the treatment of diseases, disorders or conditions mediated or treatable by inhibition of binding between WDR5 protein and its binding partners.

The present application is directed to compounds of Formula I:

##STR00001##

compounds comprising these compounds and their uses, for example as medicaments for the treatment of diseases, disorders or conditions mediated or treatable by inhibition of binding between WDR5 protein and its binding partners.

Compounds of formula (1) comprising a pleuromutilin backbone with a triazole based side-group at C22 are provided. The compounds can be used for treatment of bacterial infections and fungal infections. Importantly, infections caused by multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) may be treated effectively.

##STR00001##

Compounds of formula (1) comprising a pleuromutilin backbone with a triazole based side-group at C22 are provided. The compounds can be used for treatment of bacterial infections and fungal infections. Importantly, infections caused by multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) may be treated effectively.

##STR00001##

Compounds of the formula (I):

##STR00001##

wherein A and B together represent an optionally substituted, fused aromatic ring; X can be NR.sup.X or CR.sup.XR.sup.Y; if X=NR.sup.X then n is 1 or 2 and if X=CR.sup.XR.sup.Y then n is 1; R.sup.X is selected from the group consisting of H, optionally substituted C.sub.1-20 alkyl, C.sub.5-20 aryl, C.sub.3-20 heterocyclyl, amido, thioamido, ester, acyl, and sulfonyl groups; R.sup.Y is selected from H, hydroxy, amino; or R.sup.X and R.sup.Y may together form a spiro-C.sub.3-7 cycloalkyl or heterocyclyl group; R.sup.C1 and R.sup.C2 are both hydrogen, or when X is CR.sup.XR.sup.Y, R.sup.C1, R.sup.C2, R.sup.X and R.sup.Y, together with the carbon atoms to which they are attached, may form an optionally substituted fused aromatic ring; and
R.sup.1 is selected from H and halo.

Compounds of the formula (I):

##STR00001##

wherein A and B together represent an optionally substituted, fused aromatic ring; X can be NR.sup.X or CR.sup.XR.sup.Y; if X=NR.sup.X then n is 1 or 2 and if X=CR.sup.XR.sup.Y then n is 1; R.sup.X is selected from the group consisting of H, optionally substituted C.sub.1-20 alkyl, C.sub.5-20 aryl, C.sub.3-20 heterocyclyl, amido, thioamido, ester, acyl, and sulfonyl groups; R.sup.Y is selected from H, hydroxy, amino; or R.sup.X and R.sup.Y may together form a spiro-C.sub.3-7 cycloalkyl or heterocyclyl group; R.sup.C1 and R.sup.C2 are both hydrogen, or when X is CR.sup.XR.sup.Y, R.sup.C1, R.sup.C2, R.sup.X and R.sup.Y, together with the carbon atoms to which they are attached, may form an optionally substituted fused aromatic ring; and
R.sup.1 is selected from H and halo.

An organic compound represented by the following general formula [1] is excellent in thermal stability. ##STR00001##
In the general formula [1], R.sub.1 to R.sub.12 are each independently selected from the group consisting of a hydrogen atom and a substituent. Symbol A is selected from the group consisting of a divalent residue of naphthalene, phenanthrene, fluorene, benzofluorene, dibenzofluorene or spirofluorene, and a heteroarylene group having 4 to 12 carbon atoms. Symbol B is selected from the group consisting of an arylene group having 6 to 25 carbon atoms and a heteroarylene group having 4 to 12 carbon atoms. Symbol n is an integer of 0 to 3.