The present invention relates to inhibitors of histone deacetylases, in particular HDAC8, that are useful for the treatment of cancer and other diseases and disorders, as well as the synthesis and applications of said inhibitors.

These compounds are glutamine transporter inhibitors, e.g., alanine, serine, cysteine-preferring transporter 2 (ASCT2) inhibitors. Glutamine transporter inhibitors are useful to treat a variety of diseases, disorders, or conditions including cancer.

These compounds are glutamine transporter inhibitors, e.g., alanine, serine, cysteine-preferring transporter 2 (ASCT2) inhibitors. Glutamine transporter inhibitors are useful to treat a variety of diseases, disorders, or conditions including cancer.

Compounds of formula (I) inhibit HDAC activity: ##STR00001##
wherein A, B and D independently represent ═C— or ═N—; W is a divalent radical —CH═CH— or CH.sub.2CH.sub.2—; R.sub.1 is an ester group; R.sub.2 is the side chain of a natural or non-natural alpha-amino acid; z is 0 or 1; and Y, L.sup.1, and X.sup.1 are as defined in the claims.

Compounds of formula (I) inhibit HDAC activity: ##STR00001##
wherein A, B and D independently represent ═C— or ═N—; W is a divalent radical —CH═CH— or CH.sub.2CH.sub.2—; R.sub.1 is an ester group; R.sub.2 is the side chain of a natural or non-natural alpha-amino acid; z is 0 or 1; and Y, L.sup.1, and X.sup.1 are as defined in the claims.

A heterocyclic derivative represented by formula (I), or a pharmaceutically acceptable salt or a stereoisomer thereof, which has an inhibitory effect on the activation of STAT3 protein, and is useful for the prevention or treatment of diseases associated with the activation of STAT3 protein.

A heterocyclic derivative represented by formula (I), or a pharmaceutically acceptable salt or a stereoisomer thereof, which has an inhibitory effect on the activation of STAT3 protein, and is useful for the prevention or treatment of diseases associated with the activation of STAT3 protein.

The present invention provides acyl sulfonamide compounds of general formula (I):

##STR00001## in which X, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6′ R.sup.a and R.sup.b are as described and 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 or prophylaxis of diseases, in particular of hyperproliferative disorders, as a sole agent or in combination with other active ingredients as well as methods of treating and/or prophylaxing diseases, particularly cancer, more particularly cancer in which KAT6A and/or KAT6B is focally amplified, said method comprising administering an effective amount of at least one compound of formula (I) to a subject in need thereof.

The present invention provides acyl sulfonamide compounds of general formula (I):

##STR00001## in which X, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6′ R.sup.a and R.sup.b are as described and 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 or prophylaxis of diseases, in particular of hyperproliferative disorders, as a sole agent or in combination with other active ingredients as well as methods of treating and/or prophylaxing diseases, particularly cancer, more particularly cancer in which KAT6A and/or KAT6B is focally amplified, said method comprising administering an effective amount of at least one compound of formula (I) to a subject in need thereof.

The disclosure provides in one aspect a method of treating, ameliorating, and/or preventing toxicity caused by a ribosome inactivating protein (RIP) in a subject. In certain embodiments, the method comprises administering to the subject a therapeutically effective amount of at least one compound of the disclosure.