This application describes a compound represented by Formula (I):
YZX.sup.1S(O)(X.sup.2)F).sub.m].sub.n(I)
wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X.sup.1 is a covalent bond or CH.sub.2CH.sub.2, X.sup.2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.

A non-leaching mediator may include a polymer having a polymeric backbone, and a plurality of phenothiazine groups bonded to the polymeric backbone. The plurality of phenothiazine groups may include at least one of a phenothiazine group having the general formula (IV):

##STR00001##

and salts thereof, where n is about 9 and R represents the polymeric backbone to which the phenothiazine group is bonded, and a phenothiazine group having the general formula (V):

##STR00002##

and salts thereof, where n is about 9 and R represents the polymeric backbone to which the phenothiazine group is bonded.

A non-leaching mediator may include a polymer having a polymeric backbone, and a plurality of phenothiazine groups bonded to the polymeric backbone. The plurality of phenothiazine groups may include at least one of a phenothiazine group having the general formula (IV):

##STR00001##

and salts thereof, where n is about 9 and R represents the polymeric backbone to which the phenothiazine group is bonded, and a phenothiazine group having the general formula (V):

##STR00002##

and salts thereof, where n is about 9 and R represents the polymeric backbone to which the phenothiazine group is bonded.

The present disclosure provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula (I) wherein variables A, R.sup.1, R.sup.2, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 of Formula (I) are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to A plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, and other central nervous system conditions.

##STR00001##

A non-leaching mediator may include a polymer having a polymeric backbone, and a plurality of phenothiazine groups bonded to the polymeric backbone. The plurality of phenothiazine groups may include at least one of a phenothiazine group having the general formula (IV): ##STR00001##
and salts thereof, where n is about 9 and R represents the polymeric backbone to which the phenothiazine group is bonded, and a phenothiazine group having the general formula (V): ##STR00002##
and salts thereof, where n is about 9 and R represents the polymeric backbone to which the phenothiazine group is bonded.

A non-leaching mediator may include a polymer having a polymeric backbone, and a plurality of phenothiazine groups bonded to the polymeric backbone. The plurality of phenothiazine groups may include at least one of a phenothiazine group having the general formula (IV): ##STR00001##
and salts thereof, where n is about 9 and R represents the polymeric backbone to which the phenothiazine group is bonded, and a phenothiazine group having the general formula (V): ##STR00002##
and salts thereof, where n is about 9 and R represents the polymeric backbone to which the phenothiazine group is bonded.

The present invention relates to the treatment of cancer using combination therapy comprising a dual modulator of Insulin Receptor Substrate (IRS) and signal transducer and activator of transcription 3 (Stat3), in combination with an antibody against programmed cell death 1 (PD-1) protein, an anti-programmed cell death protein 1 ligand (PD-L1) antibody, or a combination thereof. The combination can be used to re-sensitize a tumor that may develop or has developed resistance to the anti-PD-1 and/or anti-PD-L1 antibody, by enhancing response of the tumor to the anti-PD-1 and/or anti-PD-L1 antibody, converting non-responding tumors to responders and/or blocking tumor progression.

The present invention relates to the treatment of cancer using combination therapy comprising a dual modulator of Insulin Receptor Substrate (IRS) and signal transducer and activator of transcription 3 (Stat3), in combination with an antibody against programmed cell death 1 (PD-1) protein, an anti-programmed cell death protein 1 ligand (PD-L1) antibody, or a combination thereof. The combination can be used to re-sensitize a tumor that may develop or has developed resistance to the anti-PD-1 and/or anti-PD-L1 antibody, by enhancing response of the tumor to the anti-PD-1 and/or anti-PD-L1 antibody, converting non-responding tumors to responders and/or blocking tumor progression.

2-homopiperazine-1-yl-4H-1, 3-bensothiazine-4-one derivatives of formula (I) are provided. They are useful in the treatment of bacterial infections, in particular tuberculosis, buruli ulcer and leprosy. A process for the preparation of 2-(homo)piperazine 1, 3-benzothiazine-4-one hydrochlorides is also provided.

2-homopiperazine-1-yl-4H-1, 3-bensothiazine-4-one derivatives of formula (I) are provided. They are useful in the treatment of bacterial infections, in particular tuberculosis, buruli ulcer and leprosy. A process for the preparation of 2-(homo)piperazine 1, 3-benzothiazine-4-one hydrochlorides is also provided.