This invention relates to pharmaceutical compositions comprising a selective androgen receptor modulator (SARM) compound of Formulae I-XIV and an additional therapeutic agent and uses thereof for treating a breast cancer. The method of the treatment of the invention, in some embodiments, further comprises a step, prior to the treatment, of prescreening a breast cancer subject for whether the breast cancer is susceptible to selective androgen receptor modulator (SARM) treatment.

This invention relates to pharmaceutical compositions comprising a selective androgen receptor modulator (SARM) compound of Formulae I-XIV and an additional therapeutic agent and uses thereof for treating a breast cancer. The method of the treatment of the invention, in some embodiments, further comprises a step, prior to the treatment, of prescreening a breast cancer subject for whether the breast cancer is susceptible to selective androgen receptor modulator (SARM) treatment.

A compound, or a pharmaceutically acceptable salt thereof, having a structure of:

##STR00001##

wherein A is a ring; Y.sup.1 and Y.sup.2 are each independently N or C with the proper valency; X.sup.1 and X.sup.2 are each independently —NH—, —O—, —CH.sub.2—O—, —NH—CH.sub.2—, or —N(CH.sub.3)—CH.sub.2—, provided that when at least one of X.sup.1 and X.sup.2 is —CH.sub.2—O—, —NH—CH.sub.2—, or —N(CH.sub.3)—CH.sub.2— then the —CH.sub.2— is directly connected to A; a and b are each independently 0 or 1; c and d are each independently 0 or 1; Z.sup.1 and Z.sup.2 are each independently a heterocyclic; and R.sup.1 and R.sup.2 are each independently optionally substituted alkyl, optionally substituted aralkyl, optionally substituted cycloalkyl, amino, optionally substituted heteroaralkyl, optionally substituted alkylalkoxy, optionally substituted alkylaryloxy, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocycloalkyl; provided that if Y.sup.1 and Y.sup.2 are each C, then a is 1 and b is 1; provided that if Y.sup.1 and Y.sup.2 are each N, then a is 0 and b is 0; provided that if Y.sup.1 is N and Y.sup.2 is C, then a=0 and b=1; provided that if Y.sup.1 is C and Y.sup.2 is N, then a=1 and b=0; provided that if c=0 and d=0, then R.sup.1 and R.sup.2 are both amino; provided that if c is 1 and d is 1, then both R.sup.1 and R.sup.2 are not amino; provided that if c is 0 and d is 1, then R.sup.1 is amino and R.sup.2 is optionally substituted alkyl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted heteroaralkyl, optionally substituted alkylalkoxy, optionally substituted alkylaryloxy, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocycloalkyl; and provided that if c is 1 and d is 0, then R.sup.2 is amino and R.sup.1 is optionally substituted alkyl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted heteroaralkyl, optionally substituted alkylalkoxy, optionally substituted alkylaryloxy, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocycloalkyl.

A compound, or a pharmaceutically acceptable salt thereof, having a structure of:

##STR00001##

wherein A is a ring; Y.sup.1 and Y.sup.2 are each independently N or C with the proper valency; X.sup.1 and X.sup.2 are each independently —NH—, —O—, —CH.sub.2—O—, —NH—CH.sub.2—, or —N(CH.sub.3)—CH.sub.2—, provided that when at least one of X.sup.1 and X.sup.2 is —CH.sub.2—O—, —NH—CH.sub.2—, or —N(CH.sub.3)—CH.sub.2— then the —CH.sub.2— is directly connected to A; a and b are each independently 0 or 1; c and d are each independently 0 or 1; Z.sup.1 and Z.sup.2 are each independently a heterocyclic; and R.sup.1 and R.sup.2 are each independently optionally substituted alkyl, optionally substituted aralkyl, optionally substituted cycloalkyl, amino, optionally substituted heteroaralkyl, optionally substituted alkylalkoxy, optionally substituted alkylaryloxy, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocycloalkyl; provided that if Y.sup.1 and Y.sup.2 are each C, then a is 1 and b is 1; provided that if Y.sup.1 and Y.sup.2 are each N, then a is 0 and b is 0; provided that if Y.sup.1 is N and Y.sup.2 is C, then a=0 and b=1; provided that if Y.sup.1 is C and Y.sup.2 is N, then a=1 and b=0; provided that if c=0 and d=0, then R.sup.1 and R.sup.2 are both amino; provided that if c is 1 and d is 1, then both R.sup.1 and R.sup.2 are not amino; provided that if c is 0 and d is 1, then R.sup.1 is amino and R.sup.2 is optionally substituted alkyl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted heteroaralkyl, optionally substituted alkylalkoxy, optionally substituted alkylaryloxy, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocycloalkyl; and provided that if c is 1 and d is 0, then R.sup.2 is amino and R.sup.1 is optionally substituted alkyl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted heteroaralkyl, optionally substituted alkylalkoxy, optionally substituted alkylaryloxy, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocycloalkyl.

Disclosed are compositions comprising (a) a GPR40 agonist and (b) an SGLT2 inhibitor, and methods for treating of disorders that are affected by the modulation of the GPR40 receptor and SGLT2 transporter. Such GPR40 compounds are represented by Formula (I) as follows:

##STR00001##

wherein ring W, R.sub.1, R.sub.2, R.sub.3, R.sub.5, R.sub.6, A, and Z, are defined herein.

Disclosed are compositions comprising (a) a GPR40 agonist and (b) an SGLT2 inhibitor, and methods for treating of disorders that are affected by the modulation of the GPR40 receptor and SGLT2 transporter. Such GPR40 compounds are represented by Formula (I) as follows:

##STR00001##

wherein ring W, R.sub.1, R.sub.2, R.sub.3, R.sub.5, R.sub.6, A, and Z, are defined herein.

The present invention provides compounds of Formula I ##STR00001##
and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.

The present invention provides compounds of Formula I ##STR00001##
and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.

Compositions, systems and methods for administration of small volume sufentanil drug dosage forms to the sublingual mucosa of a subject for treatment of pain using a device are disclosed.

Compositions, systems and methods for administration of small volume sufentanil drug dosage forms to the sublingual mucosa of a subject for treatment of pain using a device are disclosed.