Substituted Quinolone Carboxylic Acids, Their Derivatives, Site of Action, And Uses Thereof

A method for the treatment of CNS disorders amenable to amelioration via modulation of the GABAA receptor complex, comprising the step of:

• administering to a patient in need of such treatment an effective amount of compound of Formula I:
• or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:
• R1 is selected from the group consisting of hydrogen;
• an optionally substituted alkyl, and aralkyl;
• each R2 is selected from the group consisting of hydrogen and optionally substituted alkyl;
• each R3 is selected from the group consisting of hydrogen, optionally substituted alkyl;
• a group OR11 and NR12R13;
• R5, R7 and R8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen;
• R9 and R10 are independently selected from the group consisting of optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl;
• or R9 and R10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• R11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl;
• R12 and R13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, aryl, cycloalkyl and cycloaralkyl;
• or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring.

A method for the treatment of anxiety and related disorders, which comprises administering to a patient in need of such treatment an effective amount of a compound of Formula I:

• or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:
• R1 is selected from the group consisting of hydrogen;
• an optionally substituted alkyl and aralkyl;
• each R2 is selected from the group consisting of hydrogen and optionally substituted alkyl;
• each R3 is selected from the group consisting of hydrogen, optionally substituted alkyl;
• a group OR11 and NR12R13;
• R5, R7 and R8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl and halogen;
• R9 and R10 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl;
• or R9 and R10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• R11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl;
• R12 and R13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, aryl, cycloalkyl and cycloaralkyl, or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• with the proviso that when R9 and R10 are taken together to form a piperazinyl ring, R7 is Cl, R3 is OR11, R11 is H, R5 and R8 are H, then R1 is not Et;
• with the further proviso that when R9 and R10 taken together to form 4-methylpiperazine, R7 is Cl, R3 is OR11, R11 is H, and R5 and R8 are H, then R1 is not Et;
• and with the further proviso that when R9 and R10 are taken together to form a morpholinyl ring, R1, R2, R5, R7, R8 are H, R3 is NR12R13 and either R12 or R13 is H, the other is not n-butyl.

A method for the treatment of convulsions, which comprises administering to a patient in need of such treatment an effective amount of a compound of Formula I:

• or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:
• R1 is selected from the group consisting of hydrogen;
• an optionally substituted alkyl, and aralkyl;
• each R2 is selected from the group consisting of hydrogen and optionally substituted alkyl;
• each R3 is selected from the group consisting of hydrogen, optionally substituted alkyl;
• a group OR11 and NR12R13;
• R5, R7 and R8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen;
• R9 and R10 are independently selected from the group consisting of hydrogen optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl;
• or R9 and R10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• R11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl;
• R12 and R13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, aryl, cycloalkyl and cycloaralkyl;
• or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• with the proviso that when R9 and R10 are taken together to form a piperazinyl ring, R7 is Cl, R3 is OR11, R11 is H, R5 and R8 are H, then R1 is not Et;
• with the further proviso that when R9 and R10 taken together to form 4-methylpiperazine, R7 is Cl, R3 is OR11, R11 is H, and R5 and R8 are H, then R1 is not Et;
• and with the further proviso that when R9 and R10 are taken together to form a morpholinyl ring, R1, R2, R5, R7, R8 are H, R3 is NR12R13 and either R12 or R13 is H, the other is not n-butyl.

A method for the treatment of insomnia, which comprises administering to a patient in need of such treatment an effective amount of compound of Formula I:

• or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:
• R1 is selected from the group consisting of hydrogen;
• an optionally substituted alkyl, and aralkyl;
• each R2 is selected from the group consisting of hydrogen and optionally substituted alkyl;
• each R3 is selected from the group consisting of hydrogen, optionally substituted alkyl, a group OR11 and NR12R13;
• R5, R7 and R8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen;
• R9 and R10 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl;
• or R9 and R10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• R11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl;
• R12 and R13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, aryl, cycloalkyl and cycloaralkyl;
• or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• with the proviso that when R9 and R10 are taken together to form a piperazinyl ring, R7 is Cl, R3 is OR11, R11 is H, R5 and R8 are H, then R1 is not Et;
• with the further proviso that when R9 and R10 taken together to form 4-methylpiperazine, R7 is Cl, R3 is OR11, R11 is H, and R5 and R8 are H, then R1 is not Et;
• and with the further proviso that when R9 and R10 are taken together to form a morpholinyl ring, R1, R2, R5, R7, R8 are H, R3 is NR12R13 and either R12 or R13 is H, the other is not n-butyl.

A method for the treatment of major depressive and bipolar disorders, which comprises administering to a patient in need of such treatment an effective amount of compound of Formula I:

• or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:
• R1 is selected from the group consisting of hydrogen;
• an optionally substituted alkyl and aralkyl;
• each R2 is selected from the group consisting of hydrogen and optionally substituted alkyl;
• each R3 is selected from the group consisting of hydrogen, optionally substituted alkyl;
• a group OR11 and NR12R13.
• R5, R7 and R8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl and halogen;
• R9 and R10 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl;
• or R9 and R10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• R11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl;
• R12 and R13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, aryl, cycloalkyl and cycloaralkyl;
• or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• with the proviso that when R9 and R10 are taken together to form a piperazinyl ring, R7 is Cl, R3 is OR11, R11 is H, R5 and R8 are H, then R1 is not Et;
• with the further proviso that when R9 and R10 taken together to form 4-methylpiperazine, R7 is Cl, R3 is OR11, R11 is H, and R5 and R8 are H, then R1 is not Et;
• and with the further proviso that when R9 and R10 are taken together to form a morpholinyl ring, R1, R2, R5, R7, R8 are H, R3 is NR12R13 and either R12 or R13 is H, the other is not n-butyl.

A method for the treatment of chronic or acute pain, which comprises administering to a patient in need of such treatment an effective amount of compound of Formula I:

• or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:
• R1 is selected from the group consisting of hydrogen;
• an optionally substituted alkyl, and aralkyl;
• each R2 is selected from the group consisting of hydrogen and optionally substituted alkyl;
• each R3 is selected from the group consisting of hydrogen, optionally substituted alkyl;
• a group OR11 and NR12R13;
• R5, R7 and R8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen;
• R9 and R10 are independently selected from the group consisting of hydrogen, optionally substituted alkyl aralkyl, cycloalkyl and cycloaralkyl;
• or R9 and R10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• R11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl;
• R12 and R13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl aryl, cycloalkyl and cycloaralkyl;
• or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• with the proviso that when R9 and R10 are taken together to form a piperazinyl ring, R7 is Cl, R3 is OR11, R11 is H, R5 and R8 are H, then R1 is not Et;
• with the further proviso that when R9 and R10 taken together to form 4-methylpiperazine, R7 is Cl, R3 is OR11, R11 is H, and R5 and R8 are H, then R1 is not Et;
• and with the further proviso that when R9 and R10 are taken together to form a morpholinyl ring, R1, R2, R5, R7, R8 are H, R3 is NR12R13 and either R12 or R13 is H, the other is not n-butyl.

A method for the treatment of neuroses, which comprises administering to a patient in need of such treatment an effective amount of compound of Formula I:

• or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:
• R1 is selected from the group consisting of hydrogen;
• an optionally substituted alkyl, and aralkyl;
• each R2 is selected from the group consisting of hydrogen and optionally substituted alkyl;
• each R3 is selected from the group consisting of hydrogen, optionally substituted alkyl;
• a group OR11 and NR12R13;
• R5, R7 and R8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen;
• R9 and R10 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl;
• or R9 and R10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• R11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl;
• R12 and R13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, aryl, cycloalkyl and cycloaralkyl;
• or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• with the proviso that when R9 and R10 are taken together to form a piperazinyl ring, R7 is Cl, R3 is OR11, R11 is H, R5 and R8 are H, then R1 is not Et;
• with the further proviso that when R9 and R10 taken together to form 4-methylpiperazine, R7 is Cl, R3 is OR11, R11 is H, and R5 and R8 are H, then R1 is not Et;
• and with the further proviso that when R9 and R10 are taken together to form a morpholinyl ring, R1, R2, R5, R7, R8 are H, R3 is NR12R13 and either R12 or R13 is H, the other is not n-butyl.

A method for the treatment of withdrawal-induced convulsions from substance abuse which comprises administering to a patient in need of such treatment an effective amount of compound of Formula I:

• or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:
• R1 is selected from the group consisting of hydrogen;
• an optionally substituted alkyl, and aralkyl;
• each R2 is selected from the group consisting of hydrogen and optionally substituted alkyl;
• each R3 is selected from the group consisting of hydrogen, optionally substituted alkyl;
• a group OR11 and NR12R13;
• R5, R7 and R8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen;
• R9 and R10 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl;
• or R9 and R10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• R11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl;
• R12 and R13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, aryl, cycloalkyl and cycloaralkyl, or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• with the proviso that when R9 and R10 are taken together to form a piperazinyl ring, R7 is Cl, R3 is OR11, R11 is H, R5 and R8 are, H, then R1 is not Et;
• with the further proviso that when R9 and R10 taken together to form 4-methylpiperazine, R7 is Cl, R3 is OR11, R11 is H, and R5 and R8 are H, then R1 is not Et;
• and with the further proviso that when R9 and R10 are taken together to form a morpholinyl ring, R1, R2, R5, R7, R8 are H, R3 is NR12R13 and either R12 or R13 is H, the other is not n-butyl.

A method for the treatment of phobias, which comprises administering to a patient in need of such treatment an effective amount of compound of Formula I:

• or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:
• R1 is selected from the group consisting of hydrogen;
• an optionally substituted alkyl, and aralkyl;
• each R2 is selected from the group consisting of hydrogen and optionally substituted alkyl;
• each R3 is selected from the group consisting of hydrogen, optionally substituted alkyl;
• a group OR11 and NR12R13;
• R5, R7 and R8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen;
• R9 and R10 are independently selected from the group consisting of hydrogen, optionally substituted alkyl aralkyl, cycloalkyl and cycloaralkyl;
• or R9 and R10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• R11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl;
• R12 and R13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, aryl, cycloalkyl and cycloaralkyl;
• or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• with the proviso that when R9 and R10 are taken together to form a piperazinyl ring, R7 is Cl, R3 is OR11, R11 is H, R5 and R8 are H, then R1 is not Et;
• with the further proviso that when R9 and R10 taken together to form 4-methylpiperazine, R7 is Cl, R3 is OR11, R11 is H, and R5 and R8 are H, then R1 is not Et;
• and with the further proviso that when R9 and R10 are taken together to form a morpholinyl ring, R1, R2, R5, R7, R8 are H, R3 is NR12R13 and either R12 or R13 is H, the other is not n-butyl.

A method for the treatment of panic disorders, which comprises administering to a patient in need of such treatment an effective amount of compound of Formula I:

• or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:
• R1 is selected from the group consisting of hydrogen;
• an optionally substituted alkyl, and aralkyl;
• each R2 is selected from the group consisting of hydrogen and optionally substituted alkyl;
• each R3 is selected from the group consisting of hydrogen, optionally substituted alkyl, a group OR11 and NR12R13;
• R5, R7 and R8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen;
• R9 and R10 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl;
• or R9 and R10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• R11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl,
• R12 and R13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, aryl, cycloalkyl and cycloaralkyl;
• or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• with the proviso that when R9 and R10 are taken together to form a piperazinyl ring, R7 is Cl, R3 is OR11, R11 is H, R5 and R8 are H, then R1 is not Et;
• with the further proviso that when R9 and R10 taken together to form 4-methylpiperazine, R7 is Cl, R3 is OR11, R11 is H, and R5 and R8 are H, then R1 is not Et;
• and with the further proviso that when R9 and R10 are taken together to form a morpholinyl ring, R1, R2, R5, R7, R8 are H, R3 is NR12R13 and either R12 or R13 is H, the other is not n-butyl.

A method for the treatment of generalized anxiety disorders which comprises administering to a patient in need of such treatment an effective amount of compound of Formula I:

• or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:
• R1 is selected from the group consisting of hydrogen;
• an optionally substituted alkyl, and aralkyl;
• each R2 is selected from the group consisting of hydrogen and optionally substituted alkyl;
• each R3 is selected from the group consisting of hydrogen, optionally substituted alkyl;
• a group OR11 and NR12R13;
• R5, R7 and R8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen;
• R9 and R10 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl;
• or R9 and R10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• R11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl;
• R12 and R13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, aryl, cycloalkyl and cycloaralkyl;
• or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• with the proviso that when R9 and R10 are taken together to form a piperazinyl ring, R7 is Cl, R3 is OR11, R11 is H, R5 and R8 are H, then R1 is not Et;
• with the further proviso that when R9 and R10 taken together to form 4-methylpiperazine, R7 is Cl, R3 is OR11, R11 is H, and R5 and R8 are H, then R1 is not Et;
• and with the further proviso that when R9 and R10 are taken together to form a morpholinyl ring, R1, R2, R5, R7, R8 are H, R3 is NR12R13 and either R12 or R13 is H, the other is not n-butyl.

A method for the treatment of obsessive-compulsive disorders which comprises administering to a patient in need of such treatment an effective amount of compound of Formula I:

• or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:
• R1 is selected from the group consisting of hydrogen;
• an optionally substituted alkyl, and aralkyl;
• each R2 is selected from the group consisting of hydrogen and optionally substituted alkyl;
• each R3 is selected from the group consisting of hydrogen, optionally substituted alkyl;
• a group OR11 and NR12R13;
• R5, R7 and R8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen;
• R9 and R10 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl;
• or R9 and R10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• R11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl:
• R12 and R13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, aryl, cycloalkyl and cycloaralkyl;
• or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• with the proviso that when R9 and R10 are taken together to form a piperazinyl ring, R7 is Cl, R3 is OR11, R11 is H, R5 and R8 are H, then R1 is not Et;
• with the further proviso that when R9 and R10 taken together to form 4-methylpiperazine, R7 is Cl, R3 is OR11, R11 is H, and R5 and R8 are H, then R1 is not Et;
• and with the further proviso that when R9 and R10 are taken together to form a morpholinyl ring, R1, R2, R5, R7, R8 are H, R3 is NR12R13 and either R12 or R13 is H, the other is not n-butyl.

A method for the treatment of post traumatic and acute stress disorders, which comprises administering to a patient in need of such treatment an effective amount of compound of Formula I:

• or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:
• R1 is selected from the group consisting of hydrogen, an optionally substituted alkyl, and aralkyl;
• each R2 is selected from the group consisting of hydrogen and optionally substituted alkyl;
• each R3 is selected from the group consisting of hydrogen, optionally substituted alkyl a group OR11 and NR12R13;
• R5, R7 and R8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen;
• R9 and R10 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl;
• or R9 and R10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• R11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl;
• R12 and R13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, aryl, cycloalkyl and cycloaralkyl;
• or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• with the proviso that when R9 and R10 are taken together to form a piperazinyl ring, R7 is Cl, R3 is OR11, R11 is H, R5 and R8 are H, then R1 is not Et;
• with the further proviso that when R9 and R10 taken together to form 4-methylpiperazine, R7 is Cl, R3 is OR11, R11 is H, and R5 and R8 are H, then R1 is not Et;
• and with the further proviso that when R9 and R10 are taken together to form a morpholinyl ring, R1, R2, R5, R7, R8 are H, R3 is NR12R13 and either R12 or R13 is H, the other is not n-butyl.

A method for the treatment of migraine pain, which comprises administering to a patient in need of such treatment an effective amount of compound of Formula I:

• or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:
• R1 is selected from the group consisting of hydrogen, an optionally substituted alkyl, and aralkyl;
• each R2 is selected from the group consisting of hydrogen and optionally substituted alkyl;
• each R3 is selected from the group consisting of hydrogen, optionally substituted alkyl, a group OR11 and NR12R13;
• R5, R7 and R8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen;
• R9 and R10 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl;
• or R9 and R10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• R11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl;
• R12 and R13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl aralkyl, aryl, cycloalkyl and cycloaralkyl;
• or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• with the proviso that when R9 and R10 are taken together to form a piperazinyl ring, R7 is Cl, R3 is OR11, R11 is H, R5 and R8 are H, then R1 is not Et;
• with the further proviso that when R9 and R10 taken together to form 4-methylpiperazine, R7 is Cl, R3 is OR11, R11 is H, and R5 and R8 are H, then R1 is not Et;
• and with the further proviso that when R9 and R10 are taken together to form a morpholinyl ring, R1, R2, R5, R7, R8 are H, R3 is NR12R13 and either R12 or R13 is H, the other is not n-butyl.

A method for the treatment of bipolar manic disorders, which comprises administering to a patient in need of such treatment an effective amount of compound of Formula I:

• or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:
• R1 is selected from the group consisting of hydrogen;
• an optionally substituted alkyl, and aralkyl;
• each R2 is selected from the group consisting of hydrogen and optionally substituted alkyl;
• each R3 is selected from the group consisting of hydrogen, optionally substituted alkyl;
• a group OR11 and NR12R13;
• R5, R7 and R8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen;
• R9 and R10 are independently selected from the group consisting of hydrogen, optionally substituted alkyl aralkyl, cycloalkyl and cycloaralkyl;
• or R9 and R10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• R11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl;
• R12 and R13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl aralkyl, aryl, cycloalkyl and cycloaralkyl;
• or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• with the proviso that when R9 and R10 are taken together to form a piperazinyl ring, R7 is Cl, R3 is OR11, R11 is H, R5 and R8 are H, then R1 is not Et;
• with the further proviso that when R9 and R10 taken together to form 4-methylpiperazine, R7 is Cl, R3 is OR11, R11 is H, and R5 and R8 are H, then R1 is not Et;
• and with the further proviso that when R9 and R10 are taken together to form a morpholinyl ring, R1, R2, R5, R7, R8 are H, R3 is NR12R13 and either R12 or R13 is H, the other is not n-butyl.

A method for the treatment of cognition deficit disorders, which comprises administering to a patient in need of such treatment an effective amount of compound of Formula I:

• or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:
• R1 is selected from the group consisting of hydrogen;
• an optionally substituted alkyl, and aralkyl;
• each R2 is selected from the group consisting of hydrogen and optionally substituted alkyl;
• each R3 is selected from the group consisting of hydrogen, optionally substituted alkyl a group OR11 and NR12R13;
• R5, R7 and R8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen,
• R9 and R10 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl;
• or R9 and R10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• R11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl;
• R12 and R13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, aryl, cycloalkyl and cycloaralkyl;
• or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• with the proviso that when R9 and R10 are taken together to form a piperazinyl ring, R7 is Cl, R3 is OR11, —R11 is H, R5 and R8 are H, then R1 is not Et;
• with the further proviso that when R9 and R10 taken together to form 4-methylpiperazine, R7 is Cl, R3 is OR11, R11 is H, and R5 and R8 are H, then R1 is not Et;
• and with the further proviso that when R9 and R10 are taken together to form a morpholinyl ring, R1, R2, R5, R7, R8 are H, R3 is NR12R13 and either R12 or R13 is H, the other is not n-butyl.

A method for the treatment of disorders such as anxiety and stress related disorders, depression and other affective disorders, epilepsy and other seizure disorders, insomnia and related sleep disorders, and acute and chronic pain by enhancement of chloride conductance through the site mediating the action of compound of Formula I

• or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:
• R1 is selected from the group consisting of hydrogen, an optionally substituted alkyl, and aralkyl;
• each R2 is selected from the group consisting of hydrogen and optionally substituted alkyl;
• each R3 is selected from the group consisting of hydrogen, optionally substituted alkyl;
• a group OR11 and NR12R13;
• R5, R7 and R8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen;
• R9 and R10 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl;
• or R9 and R10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• R11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl;
• R12 and R13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, aryl, cycloalkyl and cycloaralkyl;
• or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• with the proviso that when R9 and R10 are taken together to form a piperazinyl ring, R7 is Cl, R3 is OR11, R11 is H, R5 and R8 are H, then R1 is not Et, with the further proviso that when R9 and R10 taken together to form 4-methylpiperazine, R7 is Cl, R3 is OR11, R11 is H, and R5 and R8 are H, then R1 is not Et;
• and with the further proviso that when R9 and R10 are taken together to form a morpholinyl ring, R1, R2, R5, R7, R8 are H, R3 is NR12R13 and either R12 or R13 is H, the other is not n-butyl.

A method for the treatment of disorders related to learning and memory such as mild cognitive impairment, age related cognitive decline, senile dementia, Alzheimer's disease, sleep disorders involving reduced wakefulness such as narcolepsy and idiopathic hypersomnia by inhibition of chloride conductance through the site mediating the action of compound of Formula I

• or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:
• R1 is selected from the group consisting of hydrogen;
• an optionally substituted alkyl, and aralkyl;
• each R2 is selected from the group consisting of hydrogen and optionally substituted alkyl;
• each R3 is selected from the group consisting of hydrogen, optionally substituted alkyl:
• a group OR11 and NR12R13;
• R5, R7 and R8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen,
• R9 and R10 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl;
• or R9 and R10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• R11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl;
• R12 and R13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, aryl, cycloalkyl and cycloaralkyl;
• or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;
• with the proviso that when R9 and R10 are taken together to form a piperazinyl ring, R7 is Cl, R3 is OR11, R11 is H, R5 and R8 are H, then R1 is not Et;
• with the further proviso that when R9 and R10 taken together to form 4-methylpiperazine, R7 is Cl, R3 is OR11, R11 is H, and R5 and R8 are H, then R1 is not Et;
• and with the further proviso that when R9 and R10 are taken together to form a morpholinyl ring, R1, R2, R5, R7, R8 are H, R3 is NR12R13 and either R12 or R13 is H, the other is not n-butyl.