Compounds and methods are provided for inhibiting a PI4-kinase Methods of treating a pathogen infection and methods of treating cancer are also provided. The PI4-kinase inhibitor can be a compound that is a 5-aryl or heteroaryl-thiazole, e.g., as described herein. In certain embodiments, the PI4-kinase inhibitor is a substituted 2-amino-5-phenylthiazole or substituted 2-amino-5-pyridylthiazole compound. In some embodiments, the compounds have broad spectrum anti-infective 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 treating a subject for cancer using a PI4-kinase inhibitor. Aspects of the methods include inhibiting PI4-kinase in a cancer cell to reduce cellular proliferation.

Compounds and methods are provided for inhibiting a PI4-kinase Methods of treating a pathogen infection and methods of treating cancer are also provided. The PI4-kinase inhibitor can be a compound that is a 5-aryl or heteroaryl-thiazole, e.g., as described herein. In certain embodiments, the PI4-kinase inhibitor is a substituted 2-amino-5-phenylthiazole or substituted 2-amino-5-pyridylthiazole compound. In some embodiments, the compounds have broad spectrum anti-infective 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 treating a subject for cancer using a PI4-kinase inhibitor. Aspects of the methods include inhibiting PI4-kinase in a cancer cell to reduce cellular proliferation.

The present disclosures are directed to chlorinated tetralin compounds and pharmaceutical compositions.

The present disclosures are directed to chlorinated tetralin compounds and pharmaceutical compositions.

A method of inhibiting, reducing growth of or destroying gram positive bacteria comprising contacting the gram positive bacteria with an effective amount of a 2-(substituted-amino)-imidazole compound and with an additional antibacterial compound separately, simultaneously, or sequentially, whereby the two compounds provide an antibiotic potentiation effect against the gram-positive bacteria. The additional antibacterial compound may comprise penicillin, daptomycin, vancomycin, oxacillin, linezolid, or a related antibiotic(s).

A compound represented by Formula (I), or a salt or N-oxide compound thereof is provided.

##STR00001##

In Formula (I), A.sup.1 to A.sup.4 each independently represents a carbon atom or nitrogen atom, X.sup.1 represents a C1-6 alkyl group or the like, n represents the number of X.sup.1 groups, R.sup.1 represents a C1-6 alkylthio group or the like, and D is a group represented by Formula (D-1) or (D-2), and

##STR00002##

in Formula (D-1) and (D-2), * represents a binding position, Q represents a C1-6 alkyl group or the like, B.sup.1 and B.sup.2 each independently represents a nitrogen atom or the like, R.sup.2 represents a C1-6 alkyl group or the like that is bound to one of the nitrogen atoms in Formula (D-1), B.sup.3 and B.sup.4 each independently represents a nitrogen atom or carbon atom, R.sup.4 represents a C1-6 alkyl group or the like, and m represents the number of R.sup.4 groups.

A compound represented by Formula (I), or a salt or N-oxide compound thereof is provided.

##STR00001##

In Formula (I), A.sup.1 to A.sup.4 each independently represents a carbon atom or nitrogen atom, X.sup.1 represents a C1-6 alkyl group or the like, n represents the number of X.sup.1 groups, R.sup.1 represents a C1-6 alkylthio group or the like, and D is a group represented by Formula (D-1) or (D-2), and

##STR00002##

in Formula (D-1) and (D-2), * represents a binding position, Q represents a C1-6 alkyl group or the like, B.sup.1 and B.sup.2 each independently represents a nitrogen atom or the like, R.sup.2 represents a C1-6 alkyl group or the like that is bound to one of the nitrogen atoms in Formula (D-1), B.sup.3 and B.sup.4 each independently represents a nitrogen atom or carbon atom, R.sup.4 represents a C1-6 alkyl group or the like, and m represents the number of R.sup.4 groups.

The present disclosure compounds of the formulae:

##STR00001##

wherein the variables are defined herein, as well as pharmaceutical compositions thereof. The present disclosure also provides methods for the use of said compounds and/or pharmaceutical compositions, such as in the treatment of cancer.

The present disclosure compounds of the formulae:

##STR00001##

wherein the variables are defined herein, as well as pharmaceutical compositions thereof. The present disclosure also provides methods for the use of said compounds and/or pharmaceutical compositions, such as in the treatment of cancer.

A compound represented by Formula (I), or a salt or N-oxide compound thereof is provided. ##STR00001## In Formula (I), A.sup.1 to A.sup.4 each independently represents a carbon atom or nitrogen atom, X.sup.1 represents a C1-6 alkyl group or the like, n represents the number of X.sup.1 groups, R.sup.1 represents a C1-6 alkylthio group or the like, and D is a group represented by Formula (D-1) or (D-2), and ##STR00002## in Formula (D-1) and (D-2), * represents a binding position, Q represents a C1-6 alkyl group or the like, B.sup.1 and B.sup.2 each independently represents a nitrogen atom or the like, R.sup.2 represents a C1-6 alkyl group or the like that is bound to one of the nitrogen atoms in Formula (D-1), B.sup.3 and B.sup.4 each independently represents a nitrogen atom or carbon atom, R.sup.4 represents a C1-6 alkyl group or the like, and m represents the number of R.sup.4 groups.