8-substituted tetrahydro-beta-carbolines

A method for binding a 5-HT.sub.2A receptor in a mammal, comprising administering to the mammal a receptor-binding dose of a compound of Formula I ##STR18## wherein:

• R.sup.1 is hydrogen, C.sub.1 -C.sub.3 alkyl, substituted C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkyl-(C.sub.1 -C.sub.3)alkyl, C.sub.5 -C.sub.8 cycloalkenyl-(C.sub.1 -C.sub.3)alkyl, or C.sub.7 -C.sub.16 arylalkyl;
• R.sup.4 and R.sup.5 are independently hydrogen, C.sub.1 -C.sub.3 alkyl, C.sub.2 -C.sub.6 alkenyl, halo, halo(C.sub.1 -C.sub.6)alkyl, halo(C.sub.2 -C.sub.6)alkenyl, COR.sup.7, C.sub.1 -C.sub.10 alkanoyl, CO.sub.2 R.sup.7', (C.sub.1 -C.sub.6 alkyl).sub.m amino, NO.sub.2, --SR.sup.7, OR.sup.7, substituted C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkyl-(C.sub.1 -C.sub.3)alkyl, C.sub.5 -C.sub.8 cycloalkenyl-(C.sub.1 -C.sub.3)alkyl, or C.sub.7 -C.sub.16 arylalkyl;
• m is 1 or 2;
• R.sup.7 is hydrogen or C.sub.1 C.sub.4 alkyl;
• R.sup.7' is C.sub.1 -C.sub.4 alkyl;
• R.sup.6 is selected from the group consisting of C.sub.1 -C.sub.4 alkyl, OR.sup.5', fluoro, bromo, iodo, and chloro;
• and
• R.sup.5' is selected from the group consisting of hydrogen and C.sup.1 -C.sub.4 alkyl;
• or
• a pharmaceutically acceptable salt or solvate thereof.

A method for binding a 5-HT.sub.2C receptor in a mammal, comprising administering to the mammal a receptor-binding dose of a compound of Formula I ##STR19## wherein:

• R.sup.1 is hydrogen, C.sub.1 -C.sub.3 alkyl, substituted C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkyl-(C.sub.1 -C.sub.3)alkyl, C.sub.5 -C.sub.8 cycloalkenyl-(C.sub.1 -C.sub.3)alkyl, or C.sub.7 -C.sub.16 arylalkyl;
• R.sup.4 and R.sup.5 are independently hydrogen, C.sub.1 -C.sub.3 alkyl, C.sub.2 -C.sub.6 alkenyl, halo, halo(C.sub.1 -C.sub.6)alkyl, halo(C.sub.2 -C.sub.6)alkenyl, COR.sup.7, C.sub.1 -C.sub.10 alkanoyl, CO.sub.2 R.sup.7', (C.sub.1 -C.sub.6 alkyl).sub.m amino, NO.sub.2, --SR.sup.7, OR.sup.7, substituted C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C8 cycloalkyl-(C.sub.1 -C.sub.3)alkyl, C.sub.5 -C.sub.8 cycloalkenyl-(C.sub.1 -C.sub.3)alkyl, or C.sub.7 -C.sub.16 arylalkyl;
• m is 1 or 2;
• R.sup.7 is hydrogen or C.sub.1 -C.sub.4 alkyl;
• R.sup.7' is C.sub.1 -C.sub.4 alkyl;
• R.sup.6 is selected from the group consisting of C.sub.1 -C.sub.4 alkyl, OR.sup.5', fluoro, bromo, iodo, and chloro;
• and
• R.sup.5' is selected from the group consisting of hydrogen and C.sub.1 -C.sub.4 alkyl;
• or
• a pharmaceutically acceptable salt or solvate thereof.

A method for treating a mammal suffering from or susceptible to a condition associated with the modulation of a 5-HT.sub.2A receptor, comprising administering an effective amount of a compound of Formula I ##STR20## wherein:

• R.sup.l is hydrogen, C.sub.1 -C.sub.3 alkyl, substituted C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkyl-(C.sub.1 -C.sub.3)alkyl, C.sub.5 -C.sub.8 cycloalkenyl-(C.sub.1 -C.sub.3)alkyl, or C.sub.7 -C.sub.16 arylalkyl;
• R.sup.4 and R.sup.5 are independently hydrogen, C.sub.1 -C.sub.3 alkyl, C.sub.2 -C.sub.6 alkenyl, halo, halo(C.sub.1 -C.sub.6)alkyl, halo(C.sub.2 -C.sub.6)alkenyl, COR.sup.7, C.sub.1 -C.sub.10 alkanoyl, CO.sub.2 R.sup.7', (C.sub.1 -C.sub.6 alkyl).sub.m amino, NO.sub.2, --SR.sup.7, OR.sup.7, substituted C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkyl-(C.sub.1 -C.sub.3)alkyl, C.sub.5 -C.sub.8 cycloalkenyl-(C.sub.1 -C.sub.3)alkyl, or C.sub.7 -C.sub.16 arylalkyl;
• m is 1 or 2;
• R.sup.7 is hydrogen or C.sub.1 -C.sub.4 alkyl;
• R.sup.7' is C.sub.1 -C.sub.4 alkyl;
• R.sup.6 is selected from the group consisting of C.sub.1 -C.sub.4 alkyl, OR.sup.5', fluoro, bromo, iodo, and chloro;
• and
• R.sup.5' is selected from the group consisting of hydrogen and C.sub.1 -C.sub.4 alkyl;
• or
• a pharmaceutically acceptable salt or solvate thereof.

A method for treating a mammal suffering from or susceptible to a condition associated with the modulation of a 5-HT.sub.2C receptor, comprising administering an effective amount of a compound of Formula I ##STR21## wherein:

• R.sup.1 is hydrogen, C.sub.1 -C.sub.3 alkyl, substituted C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkyl-(C.sub.1 -C.sub.3)alkyl, C.sub.5 -C.sub.8 cycloalkenyl-(C.sub.1 -C.sub.3)alkyl, or C.sub.7 -C.sub.16 arylalkyl;
• R.sup.4 and R.sup.5 are independently hydrogen, C.sub.1 -C.sub.3 alkyl, C.sub.2 -C.sub.6 alkenyl, halo, halo(C.sub.1 -C.sub.6)alkyl, halo(C.sub.2 -C.sub.6)alkenyl, COR.sup.7, C.sub.1 -C.sub.10 alkanoyl, CO.sub.2 R.sup.7', (C.sub.1 -C.sub.6 alkyl).sub.m amino, NO.sub.2, --SR.sup.7, OR.sup.7, substituted C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkyl-(C.sub.1 -C.sub.3)alkyl, C.sub.5 -C.sub.8 cycloalkenyl-(C.sub.1 -C.sub.3)alkyl, or C.sub.7 -C.sub.16 arylalkyl;
• m is 1 or 2;
• R.sup.7 is hydrogen or C.sub.1 -C.sub.4 alkyl;
• R.sup.7' is C.sub.1 -C.sub.4 alkyl;
• R.sup.6 is selected from the group consisting of C.sub.1 -C.sub.4 alkyl, OR.sup.5', fluoro, bromo, iodo, and chloro;
• and
• R.sup.5' is selected from the group consisting of hydrogen and C.sub.1 -C.sub.4 alkyl;
• or
• a pharmaceutically acceptable salt or solvate thereof.

An article of manufacture comprising packaging material and one or more pharmaceutical agents contained within said packaging material, wherein one of said pharmaceutical agents is effective for the treatment of a condition associated with 5-HT.sub.2C modulation and is a compound of Formula I ##STR22## wherein:

• R.sup.1 is hydrogen, C.sub.1 -C.sub.3 alkyl, substituted C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkyl-(C.sub.1 -C.sub.3)alkyl, C.sub.5 -C.sub.8 cycloalkenyl-(C.sub.1 -C.sub.3)alkyl, or C.sub.7 -C.sub.16 arylalkyl;
• R.sup.4 and R.sup.5 are independently hydrogen, C.sub.1 -C.sub.3 alkyl, C.sub.2 -C.sub.6 alkenyl, halo, halo(C.sub.1 -C.sub.6)alkyl, halo(C.sub.2 -C.sub.6)alkenyl, COR.sup.7, C.sub.1 -C.sub.10 alkanoyl, CO.sub.2 R.sup.7', (C.sub.1 -C.sub.6 alkyl).sub.m amino, NO.sub.2, --SR.sup.7, OR.sup.7, substituted C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkyl-(C.sub.1 -C.sub.3)alkyl, C.sub.5 -C.sub.8 cycloalkenyl-(C.sub.1 -C.sub.3)alkyl, or C.sub.7 -C.sub.16 arylalkyl;
• m is 1 or 2;
• R.sup.7 is hydrogen or C.sub.1 -C.sub.4 alkyl;
• R.sup.7' is C.sub.1 -C.sub.4 alkyl;
• R.sup.6 is selected from the group consisting of C.sub.1 -C.sub.4 alkyl, OR.sup.5', fluoro, bromo, iodo, and chloro;
• and
• R.sup.5' is selected from the group consisting of hydrogen and C.sub.1 -C.sub.4 alkyl;
• or a pharmaceutically acceptable salt or solvate thereof;
• and
• said packaging material comprises a label which indicates that said pharmaceutical agent can be used for the treatment of a condition associated with 5-HT.sub.2C modulation.