4-(heteroaryl)-1-[(2,3-dihydro-1H-indol-1-yl)alkyl]piperidines and related compounds and their therapeutic utility

A compound of the formula:

• ##STR133## wherein, X is --O--, --S--, --NH--, or --N(R.sub.2)--;
• R.sub.2 is selected from the group consisting of lower alkyl, aryl lower alkyl, aryl, cycloalkyl, aroyl, alkanoyl, alkoxycarbonyl, and phenysulfonyl groups;
• aryl is as defined hereinafter;
• p is 1 or 2;
• Y is hydrogen, lower alkyl, hydroxy, chlorine, fluorine, bromine, iodine, lower alkoxy, trifluoromethyl, nitro, or amino;
• R.sub.1 is --CR.sub.24 R.sub.27 --(CR.sub.23 R.sub.24).sub.n --CR.sub.24 R.sub.27 -- where n is 0, 1, 2, or 3;
• or
• --CHR.sub.24 --CH.dbd.CH--CHR.sub.24 --,
• --CHR.sub.24 --C.dbd.C--CHR.sub.24 --,
• --CHR.sub.24 --CH.dbd.CH--CR.sub.23 R.sub.24 --CHR.sub.24 --,
• --CHR.sub.24 --CR.sub.23 R.sub.24 --CH.dbd.CH--CHR.sub.24 --,
• CHR.sub.24 --C.dbd.C--CR.sub.23 R.sub.24 --CHR.sub.24 --, or
• --CHR.sub.24 --CR.sub.23 R.sub.24 --C.dbd.C--CHR.sub.24 --,
• the --CH.dbd.CH-- bond being cis or trans;
• R23 is hydrogen, (C.sub.1 -C.sub.18) linear alkyl phenyl, hydroxy, (C.sub.1 -C.sub.18) alkoxy, aryloxy, aryl(C.sub.1 -C.sub.18)alkyloxy, (C.sub.1 -C.sub.18)alkanoyloxy, hydroxy(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.18)alkoxy(C.sub.1 -C.sub.6)alkyl, phenyl(C.sub.1 -C.sub.6)alkoxy, aryl(C.sub.1 -C.sub.18)alkyloxy, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.18) alkanoyloxy(C.sub.1 -C.sub.6) alkyl, or ##STR134## where Z.sub.1 is lower alkyl, --OH, lower alkoxy, --CF.sub.3, --NO.sub.2, --NH.sub.2 ;
• or halogen, and p is as previously defined;
• and
• R.sub.24 is hydrogen, (C.sub.1 -C.sub.18)linear alkyl, phenyl, hydroxy(C.sub.1 -C.sub.6 )alkyl, (C.sub.1 -C.sub.18)alkoxy(C.sub.1 -C.sub.6)alkyl, phenyl(C.sub.1 -C.sub.6)alkyloxy, aryl(C.sub.1 -C.sub.18)alkyloxy(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.18)alkanoyloxy(C.sub.1 -C.sub.6)alkyl, or ##STR135## where Z.sub.1 is as previously defined, and p is as previously defined;
• R.sub.27 is hydrogen or R.sub.24 and R.sub.24 taken together with the carbon to which they are attached form C.dbd.O or C.dbd.S;
• R.sub.4 is hydrogen, lower alkyl, lower alkoxy, hydroxy, tri(C.sub.1 -C.sub.6)alkylsilyloxy, hydroxy lower alkyl, alkanoyloxy lower alkyl, amino, mono- or dialkylamino, (C.sub.1 -C.sub.18)acyl amino, (C.sub.1 -C.sub.18)alkanoyl, trifluoromethyl, chlorine, fluorine, bromine, --O--C(.dbd.O)--(C.sub.1 -C.sub.18 straight or branched chain)alkyl or --C(.dbd.O)-aryl;
• aryl is phenyl or ##STR136## where R.sub.5 is hydrogen, lower alkoxy, hydroxy, chlorine, fluorine, bromine, iodine, lower monoalkylamino, lower dialkylamino, nitro, cyano, trifluoromethyl, or trifluoromethoxy;
• q is 1, 2, 3, or 4;
• R.sub.29 and R.sub.30 are hydrogen, (C.sub.1 -C.sub.6)alkyl, aryl(C.sub.1 -C.sub.6)alkyl, or aryl, wherein aryl is as defined above
• R.sub.31 and R.sub.32 are hydrogen, hydroxy, (C.sub.1 -C.sub.6)alkyl, aryl(C.sub.1 -C.sub.6)alkyl, aryl, hydroxymethyl, or CHOR.sub.33 where R.sub.33 is (C.sub.1 -C.sub.18)alkanoyl, wherein aryl is as defined above;
• or
• either R.sub.29 and R.sub.30 taken together or R.sub.31 and R.sub.32 taken together with the carbon group to which they are attached form a C.dbd.O or C.dbd.S group;
• and aryl is as defined above;
• and, any hydroxyl group attached to an aliphatic or aromatic carbon atom, or any primary or secondary nitrogen atom may be acylated with a (C.sub.4 -C.sub.18)carboxylic group, in addition, any nitrogen atom may alternatively be acylated with a (C.sub.4 -C.sub.18)alkoxycarbonyl group;
• all geometric, optical, and stereoisomers thereof;
• or a pharmaceutically acceptable acid addition salt thereof.