The present disclosure relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds Androgen Receptor, such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation/inhibition of Androgen Receptor.

This disclosure provides compounds and compositions and methods of using those compounds and compositions to treat diseases and disorders associated with excessive transforming growth factor-beta (TGF) activity. This disclosure also provides methods of using the compounds in combination with one or more cancer immunotherapies.

This disclosure provides compounds and compositions and methods of using those compounds and compositions to treat diseases and disorders associated with excessive transforming growth factor-beta (TGF) activity. This disclosure also provides methods of using the compounds in combination with one or more cancer immunotherapies.

The present invention relates to a compound exhibiting inhibitory activity of at least one of malate dehydrogenases I (MDH1) and malate dehydrogenases 2 (MDH2), and a pharmaceutical composition for preventing or treating cancer comprising the same as an active ingredient. The inventors of the present invention have experimentally confirmed that the compound exhibiting the MDH1 and/or MDH2 inhibitory activity has an inhibitory effect on mitochondrial respiration in cancer cells, an excellent inhibitory effect on cancer cell growth, etc. Thus, the compound of the present invention is expected to be effectively used as a pharmaceutical composition for treating cancer.

There is provided compounds of formula I (I) or pharmaceutically-acceptable salts thereof, wherein L, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and n have meanings provided in the description, which compounds are useful in the treatment of cancers.

##STR00001##

The present invention relates to a compound represented by Formula (I): ##STR00001##
wherein -L- is C(X), or the like, Z is NR.sup.5, or the like, Z.sup.A is NR.sup.5A, or the like, W is C(R.sup.8R.sup.9)n-, W.sup.A is C(R.sup.3R.sup.4)m-, B is substituted or unsubstituted aromatic carbocyclyl, or the like, Y is a bond, or the like, the ring C is a substituted or unsubstituted aromatic heterocycle, or the like, R.sup.2 is a hydrogen atom, or the like, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising thereof.

The present invention relates to a compound represented by Formula (I): ##STR00001##
wherein -L- is C(X), or the like, Z is NR.sup.5, or the like, Z.sup.A is NR.sup.5A, or the like, W is C(R.sup.8R.sup.9)n-, W.sup.A is C(R.sup.3R.sup.4)m-, B is substituted or unsubstituted aromatic carbocyclyl, or the like, Y is a bond, or the like, the ring C is a substituted or unsubstituted aromatic heterocycle, or the like, R.sup.2 is a hydrogen atom, or the like, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising thereof.

A compound represented by formula (I), wherein A.sup. represents a halogen ion, a benzenesulfonate ion, an alkylsulfonate ion or the like, X represents a halogeno group or the like, a is an integer of 0 to 4, Y represents a C1-C8 alkyl group or the like, b is an integer of 0 to 5.

##STR00001##

The disclosure provides methods of use of certain compounds that are useful for treating certain symptoms of endocrine disturbances, and in particular those associated with hot flashes.

The disclosure provides methods of use of certain compounds that are useful for treating certain symptoms of endocrine disturbances, and in particular those associated with hot flashes.