The present invention provides compounds and compositions which are positive allosteric modulators of GABA-A receptors that selectively target the peripheral nervous system and organs of the body, and which do not pass through the blood-brain barrier. The compounds and compositions of the present invention are useful for treatment of diseases or disorders which are mediated by GABA-A neuronal activity, such as, for example, visceral pain, gut motility, irritable bowel syndrome, functional abdominal pain, functional idiopathic diarrhea, inflammatory bowel diseases, drug induced pain, bile salt malabsorption, lactase or other carbohydrate intolerance.

Provided herein are small molecule active metabotropic glutamate subtype-2 and -3 receptor negative allosteric modulators (NAMs), compositions comprising the compounds, and methods of using the compounds and compositions.

Provided herein are small molecule active metabotropic glutamate subtype-2 and -3 receptor negative allosteric modulators (NAMs), compositions comprising the compounds, and methods of using the compounds and compositions.

A heterocyclic compound represented by the general formula (1) or a salt thereof:

##STR00001##

wherein m, l, and n respectively represent an integer of 1 or 2; X represents O or CH.sub.2;
R.sup.1 represents hydrogen, a lower alkyl group, a hydroxy-lower alkyl group, a protecting group, or a tri-lower alkylsilyloxy-lower alkyl group;
R.sup.2 and R.sup.3, which are the same or different, each independently represent hydrogen or a lower alkyl group; or R.sub.2 and R.sub.3 are bonded to form a cyclo-C3-C8 alkyl group; and
R.sup.4 represents an aromatic group or a heterocyclic group, wherein
the aromatic or heterocyclic group may have one or more arbitrary substituent(s).

A heterocyclic compound represented by the general formula (1) or a salt thereof:

##STR00001##

wherein m, l, and n respectively represent an integer of 1 or 2; X represents O or CH.sub.2;
R.sup.1 represents hydrogen, a lower alkyl group, a hydroxy-lower alkyl group, a protecting group, or a tri-lower alkylsilyloxy-lower alkyl group;
R.sup.2 and R.sup.3, which are the same or different, each independently represent hydrogen or a lower alkyl group; or R.sub.2 and R.sub.3 are bonded to form a cyclo-C3-C8 alkyl group; and
R.sup.4 represents an aromatic group or a heterocyclic group, wherein
the aromatic or heterocyclic group may have one or more arbitrary substituent(s).

The present invention relates to a diazepine derivative represented by the following general formula (I) (in the formula, R.sup.1 and R.sup.2 represent hydrogen atom and the like, or R.sup.1 and R.sup.2 bind together to form a naphthalene ring and the like together with the benzene ring to which they bind, R.sup.3 and R.sup.4 represent hydrogen atom and the like, R.sup.5 represents hydrogen atom and the like, R.sup.6 and R.sup.7 represent hydrogen atom and the like, X represents C, CH or N, Y represents N, NH or C(O), provided that when X is N, Y is not N or NH, and when X is C or CH, Y is not C(O), Z represents oxygen atom or sulfur atom, A represents benzene ring and the like, B represents NHC(O) and the like, D represents an atomic bond and the like, E represents an atomic bond and the like, G represents benzene which may be substituted and the like, and m represents an integer of 0 to 5) or a pharmacologically acceptable salt thereof, and a P2X4 receptor antagonist.

##STR00001##

The present invention relates to a diazepine derivative represented by the following general formula (I) (in the formula, R.sup.1 and R.sup.2 represent hydrogen atom and the like, or R.sup.1 and R.sup.2 bind together to form a naphthalene ring and the like together with the benzene ring to which they bind, R.sup.3 and R.sup.4 represent hydrogen atom and the like, R.sup.5 represents hydrogen atom and the like, R.sup.6 and R.sup.7 represent hydrogen atom and the like, X represents C, CH or N, Y represents N, NH or C(O), provided that when X is N, Y is not N or NH, and when X is C or CH, Y is not C(O), Z represents oxygen atom or sulfur atom, A represents benzene ring and the like, B represents NHC(O) and the like, D represents an atomic bond and the like, E represents an atomic bond and the like, G represents benzene which may be substituted and the like, and m represents an integer of 0 to 5) or a pharmacologically acceptable salt thereof, and a P2X4 receptor antagonist.

##STR00001##

The present invention relates to compounds of formula (I) and formula (II): ##STR00001##
and to salts thereof, wherein R.sup.1-R.sup.4 of formula (I) and R.sup.5-R.sup.6 of formula (II) have any of the values defined herein, and compositions and uses thereof. The compounds are useful as inhibitors of CBP and/or EP300. Also included are pharmaceutical compositions comprising a compound of formula (I) of formula (II), or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various CBP and/or EP300-mediated disorders.

The present invention covers 4-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine-7-carboxamide compounds of general formula (I): in which R.sup.1, R.sup.2a, R.sup.2b, R.sup.2c, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, R.sup.5 and X are as 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 cancer, as a sole agent or in combination with other active ingredients.

##STR00001##

The present invention covers 4-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine-7-carboxamide compounds of general formula (I): in which R.sup.1, R.sup.2a, R.sup.2b, R.sup.2c, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, R.sup.5 and X are as 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 cancer, as a sole agent or in combination with other active ingredients.

##STR00001##