This invention, in at least some embodiments, relates to an inventive molecule, compositions comprising same, and methods of use thereof for treatment of a neurological disorder.

This invention, in at least some embodiments, relates to an inventive molecule, compositions comprising same, and methods of use thereof for treatment of a neurological disorder.

The present invention relates to a compound of Formula 1, 2 or 3: I II III wherein A is N or —CR.sub.0—, where R.sub.0 is hydrogen, C.sub.1-C.sub.6 linear or branched chain alkyl, etc., Z is —CR.sub.e—, or, —N—, where R.sub.e is hydrogen, C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; R.sub.1 is hydrogen, C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; R.sub.2 are independently hydrogen or C.sub.1-C.sub.6 linear or branched chain alkyl; R.sub.3 and R.sub.4 are independently hydrogen, C.sub.1C.sub.6 linear or branched chain alkyl, etc.; R.sub.5 and R.sub.6 are independently hydrogen or C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; R.sub.8 is hydrogen, C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; R.sub.9 and R.sub.10 are independently hydrogen or C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; Q is —CO—, —(CH.sub.2).sub.q—, —(CHR.sub.s).sub.q—, or —(CR.sub.sR.sub.t).sub.q—, where R.sub.s and R.sub.t are independently C.sub.1-C.sub.6 linear or branched chain alkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where .sub.q is 0, 1, 2, or 3; and, where n is 0, 1, 2, 3, 4 or 5; or, a pharmaceutically acceptable salt thereof, for the treatment of certain diseases, particularly those affected or mediated by the androgen receptor; to combinations comprising such compounds with a second pharmaceutically active ingredient; to compositions containing such combinations; and to such combinations for the treatment of various diseases, particularly, those affected or mediated by the androgen receptor.

##STR00001##

The present invention relates to a compound of Formula 1, 2 or 3: I II III wherein A is N or —CR.sub.0—, where R.sub.0 is hydrogen, C.sub.1-C.sub.6 linear or branched chain alkyl, etc., Z is —CR.sub.e—, or, —N—, where R.sub.e is hydrogen, C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; R.sub.1 is hydrogen, C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; R.sub.2 are independently hydrogen or C.sub.1-C.sub.6 linear or branched chain alkyl; R.sub.3 and R.sub.4 are independently hydrogen, C.sub.1C.sub.6 linear or branched chain alkyl, etc.; R.sub.5 and R.sub.6 are independently hydrogen or C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; R.sub.8 is hydrogen, C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; R.sub.9 and R.sub.10 are independently hydrogen or C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; Q is —CO—, —(CH.sub.2).sub.q—, —(CHR.sub.s).sub.q—, or —(CR.sub.sR.sub.t).sub.q—, where R.sub.s and R.sub.t are independently C.sub.1-C.sub.6 linear or branched chain alkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where .sub.q is 0, 1, 2, or 3; and, where n is 0, 1, 2, 3, 4 or 5; or, a pharmaceutically acceptable salt thereof, for the treatment of certain diseases, particularly those affected or mediated by the androgen receptor; to combinations comprising such compounds with a second pharmaceutically active ingredient; to compositions containing such combinations; and to such combinations for the treatment of various diseases, particularly, those affected or mediated by the androgen receptor.

##STR00001##

The present invention relates to a compound of Formula 1, 2 or 3: I II III wherein A is N or —CR.sub.0—, where R.sub.0 is hydrogen, C.sub.1-C.sub.6 linear or branched chain alkyl, etc., Z is —CR.sub.e—, or, —N—, where R.sub.e is hydrogen, C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; R.sub.1 is hydrogen, C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; R.sub.2 are independently hydrogen or C.sub.1-C.sub.6 linear or branched chain alkyl; R.sub.3 and R.sub.4 are independently hydrogen, C.sub.1C.sub.6 linear or branched chain alkyl, etc.; R.sub.5 and R.sub.6 are independently hydrogen or C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; R.sub.8 is hydrogen, C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; R.sub.9 and R.sub.10 are independently hydrogen or C.sub.1-C.sub.6 linear or branched chain alkyl, etc.; Q is —CO—, —(CH.sub.2).sub.q—, —(CHR.sub.s).sub.q—, or —(CR.sub.sR.sub.t).sub.q—, where R.sub.s and R.sub.t are independently C.sub.1-C.sub.6 linear or branched chain alkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where .sub.q is 0, 1, 2, or 3; and, where n is 0, 1, 2, 3, 4 or 5; or, a pharmaceutically acceptable salt thereof, for the treatment of certain diseases, particularly those affected or mediated by the androgen receptor; to combinations comprising such compounds with a second pharmaceutically active ingredient; to compositions containing such combinations; and to such combinations for the treatment of various diseases, particularly, those affected or mediated by the androgen receptor.

##STR00001##

The present disclosure relates to mdm2 inhibitors for use in specific dosing schedules. It was found that if sufficiently potent or, in alternative, sufficiently high dose of a Mdm2 inhibitor is used, it can cause antineoplastic effect by triggering much longer lasting antiproliferative mechanism in cells. The long lasting effect can sustain for several weeks after a single dose, which eliminates the need for daily treatment and allows administering the Mdm2i intermittently. A treatment with the intermittent dosing schedule of a Mdm2 inhibitor can be combined with a daily treatment of the Mdm2i or with another pharmaceutically acceptable ingredient.

The present disclosure relates to mdm2 inhibitors for use in specific dosing schedules. It was found that if sufficiently potent or, in alternative, sufficiently high dose of a Mdm2 inhibitor is used, it can cause antineoplastic effect by triggering much longer lasting antiproliferative mechanism in cells. The long lasting effect can sustain for several weeks after a single dose, which eliminates the need for daily treatment and allows administering the Mdm2i intermittently. A treatment with the intermittent dosing schedule of a Mdm2 inhibitor can be combined with a daily treatment of the Mdm2i or with another pharmaceutically acceptable ingredient.

A medicament for treating or preventing pruritus is provided. For the medicament for treating or preventing pruritus, a compound having a blocking action on Cav3.2T-type calcium channels represented by General Formulas (I) to (VI), a tautomer of the compound, a stereoisomer of the compound, a pharmaceutically acceptable salt thereof, or a solvate thereof is used as an active ingredient.

A medicament for treating or preventing pruritus is provided. For the medicament for treating or preventing pruritus, a compound having a blocking action on Cav3.2T-type calcium channels represented by General Formulas (I) to (VI), a tautomer of the compound, a stereoisomer of the compound, a pharmaceutically acceptable salt thereof, or a solvate thereof is used as an active ingredient.

This disclosure is directed, at least in part, to GPR40 agonists useful for the treatment of conditions or disorders involving the gut-brain axis. In some embodiments, the GPR40 agonists are gut-restricted compounds. In some embodiments, the GPR40 agonists are full agonists or partial agonists. In some embodiments, the condition or disorder is a metabolic disorder, such as diabetes, obesity, nonalcoholic steatohepatitis (NASH), or a nutritional disorder such as short bowel syndrome.