Provided are compounds of Formula I, compositions and methods for their use as inhibitors of alpha-kinase 1 (ALPK1).

Provided are compounds of Formula I, compositions and methods for their use as inhibitors of alpha-kinase 1 (ALPK1).

Compounds and methods are provided for the treatment of pathogen infections. In some embodiments, the anti-infective compounds have broad spectrum activity against a variety of infective diseases, where the diseases are caused by pathogens containing a basic amino acid PIP-2 pincer (BAAPP) domain that interacts with phosphatidylinositol 4,5-bisphosphate (PIP-2) to mediate pathogen replication. Also provided are methods of inhibiting a PI4-kinase and methods of inhibiting viral infection. In some embodiments, the compound is a PI4-kinase inhibiting compound that is a 5-aryl-thiazole or a 5-hetereoaryl-thiazole. The subject compounds may be formulated or provided to a subject in combination with a second anti-infective agent, e.g. interferon, ribivarin, and the like.

Compounds and methods are provided for the treatment of pathogen infections. In some embodiments, the anti-infective compounds have broad spectrum activity against a variety of infective diseases, where the diseases are caused by pathogens containing a basic amino acid PIP-2 pincer (BAAPP) domain that interacts with phosphatidylinositol 4,5-bisphosphate (PIP-2) to mediate pathogen replication. Also provided are methods of inhibiting a PI4-kinase and methods of inhibiting viral infection. In some embodiments, the compound is a PI4-kinase inhibiting compound that is a 5-aryl-thiazole or a 5-hetereoaryl-thiazole. The subject compounds may be formulated or provided to a subject in combination with a second anti-infective agent, e.g. interferon, ribivarin, and the like.

A compound of formula (I)

##STR00001##

wherein R, R.sup.1, R.sup.2, R.sup.3, Y, Y.sup.1, a, X, and Z are as defined herein.

The compounds of the present invention are inhibitors of hematopoietic prostaglandin D synthase (H-PGDS) and can be useful in the treatment of Duchenne Muscular Dystrophy. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting H-PGDS activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

A compound represented by formula (I) or a salt thereof.

##STR00001##

In formula (I), R.sup.1 and R.sup.4 each independently represent a hydrogen atom, or an unsubstituted or substituted C1 to C6 alkyl group or the like. R.sup.2 represents a hydrogen atom, or an unsubstituted or substituted C1 to C6 alkyl group or the like. R.sup.3 represents an unsubstituted or substituted C1 to C6 alkyl group or the like. R.sup.5 represents a C1 to C6 haloalkyl group or the like. G represents an oxygen atom or a sulfur atom. R.sup.6 and R.sup.7 each independently represent a hydrogen atom, or an unsubstituted or substituted C1 to C6 alkyl group or the like. n represents 0 or 1. R.sup.8 and R.sup.9 each independently represent a hydrogen atom, or an unsubstituted or substituted C1 to C6 alkyl group. Ar represents an unsubstituted or substituted C6 to C10 aryl group or the like.

The present invention features compounds useful in the inhibition of the secretion of proteins. The compounds of the invention can be used in methods for treating diseases associated with protein secretion, and in methods for inhibiting protein secretion.

The invention provides compounds of formulae I, II, IIa, and III:

##STR00001##

and pharmaceutically acceptable salts thereof, as well as compositions containing such compounds and methods for using such compounds and compositions.

The invention provides compounds of formulae I, II, IIa, and III:

##STR00001##

and pharmaceutically acceptable salts thereof, as well as compositions containing such compounds and methods for using such compounds and compositions.

Compounds and methods are provided for the treatment of pathogen infections. In some embodiments, the anti-infective compounds have broad spectrum activity against a variety of infective diseases, where the diseases are caused by pathogens containing a basic amino acid PIP-2 pincer (BAAPP) domain that interacts with phosphatidylinositol 4,5-bisphosphate (PIP-2) to mediate pathogen replication. Also provided are methods of inhibiting a PI4-kinase and methods of inhibiting viral infection. In some embodiments, the compound is a PI4-kinase inhibiting compound that is a 5-aryl-thiazole or a 5-hetereoaryl-thiazole. The subject compounds may be formulated or provided to a subject in combination with a second anti-infective agent, e.g. interferon, ribivarin, and the like.