Methods of use of cyclic amide derivatives to treat schizophrenia

A method of treating or diminishing at least one symptom of schizophrenia in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a compound of the formula (I) or a pharmaceutically acceptable salt, hydrate, or solvate thereof,

• wherein:
• X represents an alkyl group, a cycloalkyl-substituted alkyl group, an aryl-substituted alkyl group, an aryl-substituted alkenyl group, an aryl-substituted alkynyl group, a monocyclic or polycyclic cycloalkyl group which may be substituted with an alkyl group, an aryl group, a heterocyclic group, or a substituted or unsubstituted amino group;
• Q represents a group represented by —CO—, —O—, —S—, —CH(OR)—, —C(═CH2)— or —C(═NR8)— wherein R7 represents a hydrogen atom, an alkyl group, a hydroxyalkyl group, or an acyl group, and R8 represents a hydroxyl group, an alkoxyl group, an aralkyloxy group, an acyloxy group, an acylamino group, or an alkoxycarbonyl amino group;
• n represents an integer of from. 0 to 5;
• R1 and R2 each independently represent a hydrogen atom or an alkyl group;
• B represents the following groups:
• wherein R3, R4, R5 and R6 each independently represent a substituent selected from the group consisting of a hydrogen atom, a halogen atom, a nitro group, an alkyl group, a halogenated alkyl group, a hydroxyl group, an alkoxyl group, a halogenated alkoxyl group, and a cyano group;
• m represents 1 or 2.

A method of treating at least one symptom of schizophrenia in a subject comprising administering to a subject in need thereof a composition comprising:

• (a) a therapeutically effective amount of an antipsychotic compound that is not a compound of formula (I);
• and
• (b) a therapeutically effective amount of a compound of the formula (I) or a pharmaceutically acceptable salt, hydrate, or solvate thereof,
• wherein:
• X represents an alkyl group, a cycloalkyl-substituted alkyl group, an aryl-substituted alkyl group, an aryl-substituted alkenyl group, an aryl-substituted alkynyl group, a monocyclic or polycyclic cycloalkyl group which may be substituted with an alkyl group, an aryl group, a heterocyclic group, or a substituted or unsubstituted amino group;
• Q represents a group represented by —CO—, —O—, —S—, —CH(OR7)—, —C(═CH2)— or —C(═NR8)— wherein R7 represents a hydrogen atom, an alkyl group, a hydroxyalkyl group, or an acyl group, and R8 represents a hydroxyl group, an alkoxyl group, an aralkyloxy group, an acyloxy group, an acylamino group, or an alkoxycarbonyl amino group;
• n represents an integer of from 0 to 5;
• R1 and R2 each independently represent a hydrogen atom or an alkyl group;
• B represents the following groups:
• wherein R3, R4, R5 and R6 each independently represent a substituent selected from the group consisting of a hydrogen atom, a halogen atom, a nitro group, an alkyl group, a halogenated alkyl group, a hydroxyl group, an alkoxyl group, a halogenated alkoxyl group, and a cyano group;
• m represents 1 or 2.

A method of augmenting treatment of schizophrenia in a subject presently receiving one or more compounds for the treatment of schizophrenia, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of the formula (I) or a pharmaceutically acceptable salt, hydrate, or solvate thereof,

• wherein:
• X represents an alkyl group, a cycloalkyl-substituted alkyl group, an aryl-substituted alkyl group, an aryl-substituted alkenyl group, an aryl-substituted alkynyl group, a monocyclic or polycyclic cycloalkyl group which may be substituted with an alkyl group, an aryl group, a heterocyclic group, or a substituted or unsubstituted amino group;
• Q represents a group represented by —CO—, —O—, —S—, —CH(OR7—, —C(═CH2)— or —C(═NR8)— wherein R7 represents a hydrogen atom, an alkyl group, a hydroxyalkyl group, or an acyl group, and R8 represents a hydroxyl group, an alkoxyl group, an aralkyloxy group, an acyloxy group, an acylamino group, or an alkoxycarbonyl amino group;
• n represents an integer of from 0 to 5;
• R1 and R2 each independently represent a hydrogen atom or an alkyl group;
• B represents the following groups:
• wherein R3, R4, R5 and R6 each independently represent a substituent selected from the group consisting of a hydrogen atom, a halogen atom, a nitro group, an alkyl group, a halogenated alkyl group, a hydroxyl group, an alkoxyl group, a halogenated alkoxyl group, and a cyano group;
• m represents 1 or 2,
• wherein prior to the augmented treatment of the subject, the treatment of the subject did not comprise administration of a compound of formula (I).

A method of treating or improving at least one disorder or parameter of sleep in a subject comprising administering to a subject in need thereof a composition comprising:

• (a) a therapeutically effective amount of an antipsychotic compound that is not a compound of formula (I);
• and
• (b) a therapeutically effective amount of a compound of the formula (I) or a pharmaceutically acceptable salt, hydrate, or solvate thereof,
• wherein:
• X represents an alkyl group, a cycloalkyl-substituted alkyl group, an aryl-substituted alkyl group, an aryl-substituted alkenyl group, an aryl-substituted alkynyl group, a monocyclic or polycyclic cycloalkyl group which may be substituted with an alkyl group, an aryl group, a heterocyclic group, or a substituted or unsubstituted amino group;
• Q represents a group represented by —CO—, —O—, —S—, —CH(OR7)—, —C(═CH2)— or —C(═NR8)— wherein R7 represents a hydrogen atom, an alkyl group, a hydroxyalkyl group, or an acyl group, and R8 represents a hydroxyl group, an alkoxyl group, an aralkyloxy group, an acyloxy group, an acylamino group, or an alkoxycarbonyl amino group;
• n represents an integer of from 0 to 5;
• R1 and R2 each independently represent a hydrogen atom or an alkyl group;
• B represents the following groups:
• wherein R3, R4, R5 and R6 each independently represent a substituent selected from the group consisting of a hydrogen atom, a halogen atom, a nitro group, an alkyl group, a halogenated alkyl group, a hydroxyl group, an alkoxyl group, a halogenated alkoxyl group, and a cyano group;
• m represents 1 or 2,
• wherein the therapeutically effective amount of an antipsychotic compound that is not a compound of formula (I) is lower than it would otherwise be in the absence of the compound of formula (I).

A method of treating schizophrenia-related cognitive skills in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a compound of the formula (I) or a pharmaceutically acceptable salt, hydrate, or solvate thereof,

• wherein:
• X represents an alkyl group, a cycloalkyl-substituted alkyl group, an aryl-substituted alkyl group, an aryl-substituted alkenyl group, an aryl-substituted alkynyl group, a monocyclic or polycyclic cycloalkyl group which may be substituted with an alkyl group, an aryl group, a heterocyclic group, or a substituted or unsubstituted amino group;
• Q represents a group represented by —CO—, —O—, —S—, —CH(OR7)—, —C(═CH2)— or —C(═NR8)— wherein R7 represents a hydrogen atom, an alkyl group, a hydroxyalkyl group, or an acyl group, and R8 represents a hydroxyl group, an alkoxyl group, an aralkyloxy group, an acyloxy group, an acylamino group, or an alkoxycarbonyl amino group;
• n represents an integer of from 0 to 5;
• R1 and R2 each independently represent a hydrogen atom or an alkyl group;
• B represents the following groups:
• wherein R3, R4, R5 and R6 each independently represent a substituent selected from the group consisting of a hydrogen atom, a halogen atom, a nitro group, an alkyl group, a halogenated alkyl group, a hydroxyl group, an alkoxyl group, a halogenated alkoxyl group, and a cyano group;
• m represents 1 or 2.

A method of treating schizophrenia or of treating or diminishing at least one symptom of schizophrenia in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a compound of the formula (I) or a pharmaceutically acceptable salt, hydrate, or solvate thereof,

• wherein:
• X represents an alkyl group, a cycloalkyl-substituted alkyl group, an aryl-substituted alkyl group, an aryl-substituted alkenyl group, an aryl-substituted alkynyl group, a monocyclic or polycyclic cycloalkyl group which may be substituted with an alkyl group, an aryl group, a heterocyclic group, or a substituted or unsubstituted amino group;
• Q represents a group represented by —CO—, —O—, —S—, —CH(OR7)—, —C(═CH2)— or —C(═NR8)— wherein R7 represents a hydrogen atom, an alkyl group, a hydroxyalkyl group, or an acyl group, and R8 represents a hydroxyl group, an alkoxyl group, an aralkyloxy group, an acyloxy group, an acylamino group, or an alkoxycarbonyl amino group;
• n represents an integer of from 0 to 5;
• R1 and R2 each independently represent a hydrogen atom or an alkyl group;
• B represents the following groups:
• wherein R3, R4, R5 and R6 each independently represent a substituent selected from the group consisting of a hydrogen atom, a halogen atom, a nitro group, an alkyl group, a halogenated alkyl group, a hydroxyl group, an alkoxyl group, a halogenated alkoxyl group, and a cyano group;
• m represents 1 or 2.