Method for treating 5HT.sub.2B receptor related conditions

A method for blocking a 5-HT.sub.2B receptor in a mammal comprising administering to the mammal a 5-HT.sub.2B receptor-blocking dose of a compound of Formula I:

• ##STR195## wherein:
• Q is hydrogen or (CHR.sub.2)R.sub.4
• R.sub.1 is hydrogen or C.sub.1 -C.sub.3 alkyl;
• R.sub.2 is hydrogen or C.sub.1 -C.sub.6 alkyl;
• R.sub.3 is hydrogen or C.sub.1 -C.sub.3 alkyl;
• R.sub.4 is C.sub.5 -C.sub.8 cycloalkyl, substituted C.sub.5 -C.sub.8 cycloalkyl, C.sub.5 -C.sub.8 cycloalkenyl, substituted C.sub.5 -C.sub.8 cycloalkenyl, bicyclic or substituted bicyclic;
• A is selected from the group consisting of ##STR196## wherein R.sub.6 and R.sub.7 are, independently, hydrogen, C.sub.1 -C.sub.6 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.sub.5, C.sub.1 -C.sub.10 alkanoyl, CO.sub.2 R.sub.5', (C.sub.1 -C.sub.6 alkyl).sub.m amino, NO.sub.2, -SR.sub.5, or OR.sub.5 ;
• or
• R.sub.6 and R.sub.7 together with the carbon atoms of group A form a 5- to 8-member carbon ring;
• m is 1 or 2;
• R.sub.5 is hydrogen or C.sub.1 -C.sub.4 alkyl;
• R.sub.5' is C.sub.1 -C.sub.4 alkyl;
• and
• R.sub.8 is an R.sub.6 group, substituted C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cyctoalkyl, C.sub.3 -C.sub.8 cycloalkyl (C.sub.1 C.sub.3)alkyl, C.sub.5 C.sub.8 cycloalkenyl, substituted C.sub.5 -C.sub.8 cycloalkenyl, C.sub.5 -C.sub.8 cycloalkenyl-(C.sub.1 -C.sub.3)alkyl, or C.sub.7 -C.sub.20 arylalkyl;
• or a pharmaceutically acceptable salt or solvate thereof.

A method for selectively blocking a 5-HT.sub.2B receptor in a mammal comprising administering to the mammal a 5-HT.sub.2B selective compound of Formula I:

• ##STR197## wherein:
• Q is hydrogen or (CHR.sub.2)R.sub.4
• R.sub.1 is hydrogen or C.sub.1 -C.sub.3 alkyl;
• R.sub.2 is hydrogen or C.sub.1 -C.sub.6 alkyl;
• R.sub.3 is hydrogen or C.sub.1 -C.sub.3 alkyl;
• R.sub.4 is C.sub.5 -C.sub.8 cycloalkyl, substituted C.sub.5 -C.sub.8 cycloalkyl, C.sub.5 -C.sub.8 cycloalkenyl, substituted C.sub.5 -C.sub.8 cycloalkenyl, bicyclic or substituted bicyclic;
• A is selected from the group consisting of ##STR198## wherein R.sub.6 and R.sub.7 are, independently, hydrogen, C.sub.1 -C.sub.6 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.sub.5, C.sub.1 -C.sub.10 alkanoyl, CO.sub.2 R.sub.5', (C.sub.1 -C.sub.6 alkyl).sub.m amino, NO.sub.2, -SR.sub.5, or OR.sub.5 ;
• or
• R.sub.6 and R.sub.7 together with the carbon atoms of group A form a 5- to 8-member carbon ring;
• m is 1 or 2;
• R.sub.5 is hydrogen or C.sub.1 -C.sub.4 alkyl;
• R.sub.5' is C.sub.1 -C.sub.4 alkyl;
• and
• R.sub.8 is an R.sub.6 group, 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, substituted C.sub.5 -C.sub.8 cycloalkenyl, C.sub.5 -C.sub.8 cycloalkenyl-(C.sub.1 -C.sub.3)alkyl, or C.sub.7 -C.sub.20 arylalkyl;
• or a pharmaceutically acceptable salt or solvate thereof.

An article of manufacture comprising a pharmaceutical agent of Formula I:

• ##STR199## wherein:
• Q is hydrogen or (CHR.sub.2) R.sub.4
• R.sub.1 is hydrogen or C.sub.1 -C.sub.3 alkyl;
• R.sub.2 is hydrogen or C.sub.1 -C.sub.6 alkyl;
• R.sub.3 is hydrogen or C.sub.1 -C.sub.3 alkyl;
• R.sub.4 is C.sub.5 -C.sub.8 cycloalkyl, substituted C.sub.5 -C.sub.8 cycloalkyl, C.sub.5 -C.sub.8 cycloalkenyl, substituted C.sub.5 -C.sub.8 cycloalkenyl, bicyclic or substituted bicyclic;
• A is selected from the group consisting of ##STR200## wherein R.sub.6 and R.sub.7 are, independently, hydrogen, C.sub.1 -C.sub.6 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.sub.5, C.sub.1 -C.sub.10 alkanoyl, CO.sub.2 R.sub.5', (C.sub.1 -C.sub.6 alkyl).sub.m amino, NO.sub.2, -SR.sub.5, or OR.sub.5 ;
• or
• R.sub.6 and R.sub.7 together with the carbon atoms of group A form a 5- to 8-member carbon ring;
• m is 1 or 2;
• R.sub.5 is hydrogen or C.sub.1 -C.sub.4 alkyl;
• R.sub.5' is C.sub.1 -C.sub.4 alkyl;
• and
• R.sub.8 is an R.sub.6 group, 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, substituted C.sub.5 -C.sub.8 cycloalkenyl, C.sub.5 -C.sub.8 cycloalkenyl-(C.sub.1 C.sub.3)alkyl, or C.sub.7 -C.sub.20 arylalkyl;
• or a pharmaceutically acceptable salt or solvate thereof, contained in a packaging material that has a label indicating that the pharmaceutical agent can be used for treating a condition associated with dysfunctional or abnormal 5-HT.sub.2B receptor stimulation.