.beta..sub.3 -Adrenoceptor agonists and antagonists for the treatment of intestinal motility disorders, depression, prostate disease and dyslipidemia

A method of treating a condition selected from the group consisting of intestinal motility disorders, intestinal ulcerations including inflammatory bowel disease, ulcerative colitis, Crohn's disease and proctitis, gastrointestinal ulcerations, depression, prostate disease, and dyslipidemia in a mammal comprising administering to a mammal in need of said treatment an amount of a .beta..sub.3 -adrenoceptor antagonist or agonist formula ##STR29## wherein R.sup.1 is phenyl, --(CH.sub.2).sub.n --O-phenyl or thiazolyl, wherein said phenyl, the phenyl moiety of said --(CH.sub.2).sub.n --O-phenyl and said thiazolyl may optionally be substituted with one or more substituents, independently selected from hydrogen, (C.sub.1 -C.sub.6) alkyl optionally substituted with one or more halo atoms, hydroxy, (C.sub.1 -C.sub.6) alkoxy optionally substituted with one or more halo atoms, (C.sub.1 -C.sub.6) alkylthio, fluoro, chloro, bromo, iodo, nitro and cyano;

• R.sup.2 is hydrogen or (C.sub.1 -C.sub.6) alkyl optionally substituted with one or more halo atoms;
• R.sup.3 is hydrogen, --(CH.sub.2).sub.n -phenyl, --(C.sub.1 -C.sub.10) alkyl, --(CH.sub.2).sub.n --NR.sup.7 R.sup.8, --(CH.sub.2).sub.n --CO.sub.2 R.sup.11, ##STR30## --(CH.sub.2).sub.n --OR.sup.11, --(CH.sub.2).sub.n --SO.sub.3 R.sup.11, --(CH.sub.2).sub.n --SO.sub.2 --(C.sub.1 -C.sub.6) alkyl, --(CH.sub.2).sub.n --SO.sub.2 NR.sup.7 R.sup.8, or a heterocycle selected from --(CH.sub.2).sub.n -pyridyl, --(CH.sub.2).sub.n -pyrimidyl, --(CH.sub.2).sub.n -pyrazinyl, --(CH.sub.2).sub.n -isoxazolyl, --(CH.sub.2).sub.n -oxazolyl, --(CH.sub.2).sub.n -thiazolyl, --(CH.sub.2).sub.n -(1,2,4-oxadiazolyl), --(CH.sub.2).sub.n -imidazolyl, --(CH.sub.2).sub.n -triazolyl and --(CH.sub.2).sub.n -tetrazolyl, wherein one of the ring nitrogen atoms of said --(CH.sub.2).sub.n -imidazolyl, --(CH.sub.2).sub.n -triazolyl or --(CH.sub.2).sub.n -tetrazolyl may optionally be substituted by (C.sub.1 -C.sub.6) alkyl optionally substituted with one or more halo atoms, and wherein each of said heterocycles may optionally be substituted on one or more of the ring carbon atoms by (C.sub.1 -C.sub.6) alkyl optionally substituted with one or more halo atoms halo, nitro, cyano, --(CH.sub.2).sub.n --NR.sup.7 R.sup.8, --(CH.sub.2).sub.n --CO.sub.2 R.sup.11, ##STR31## --(CH.sub.2).sub.n --OR.sup.11, --(CH.sub.2).sub.n --SO.sub.2 R.sup.11, --(CH.sub.2).sub.n --SO.sub.2 --(C.sub.1 -C.sub.6) alkyl, or --(CH.sub.2).sub.n --SO.sub.2 NR.sup.7 R.sup.8, and wherein the phenyl moiety of said (CH.sub.2).sub.n -phenyl may optionally be substituted with one or more substituents independently selected from (C.sub.1 -C.sub.6)alkyl optionally substituted with one or more halo atoms hydroxy, (C.sub.1 -C.sub.6)alkoxy optionally substituted with one or more halo atoms, (C.sub.1 -C.sub.6)alkylthio, fluoro, chloro, bromo, iodo, cyano, nitro, --(CH.sub.2).sub.n --NR.sup.7 R.sup.8, --(CH.sub.2).sub.n --CO.sub.2 R.sup.11, ##STR32## --(CH.sub.2).sub.n --OR.sup.11, --(CH.sub.2).sub.n --SO.sub.3 R.sup.11, --(CH.sub.2).sub.n --SO.sub.2 --(C.sub.1 -C.sub.6)alkyl, and --(CH.sub.2).sub.n --SO.sub.2 NR.sup.7 R.sup.8 ;
• R.sup.4 is --(CH.sub.2).sub.n --CN, --(CH.sub.2).sub.n CO.sub.2 R.sup.11, --(CH.sub.2).sub.n --SO.sub.3 R.sup.11, --(CH.sub.2).sub.n --SO.sub.2 --(C.sub.1 -C.sub.6)alkyl, --(CH.sub.2).sub.n --SO.sub.2 --NR.sup.7 R.sup.8, --(CH.sub.2).sub.n CH.sub.2 OH optionally substituted with a suitable protecting group, --(CH.sub.2).sub.n --CHO, --(CH.sub.2).sub.n --C(.dbd.O)R.sup.11, --(CH.sub.2).sub.n --C(.dbd.O)NR.sup.7 R.sup.8, or a heterocycle selected from --(CH.sub.2).sub.n -thiazolyl, --(CH.sub.2).sub.n -oxazolyl, --(CH.sub.2).sub.n -imidazolyl, --(CH.sub.2).sub.n -triazolyl, --(CH.sub.2).sub.n -1,2,4-oxadiazolyl, --(CH.sub.2).sub.n -isoxazolyl, --(CH.sub.2).sub.n -tetrazolyl and --(CH.sub.2).sub.n -pyrazolyl;
• wherein one of the ring nitrogen atoms of said --(CH.sub.2).sub.n -imidazolyl, --(CH.sub.2).sub.n -triazolyl and --(CH.sub.2).sub.n -tetrazolyl may optionally be substituted by (C.sub.1 -C.sub.6)alkyl optionally substituted with one or more halo atoms, wherein each of said heterocycles may optionally be substituted on any of the ring carbon atoms by hydrogen, (C.sub.1 -C.sub.6)alkyl optionally substituted with one or more halo atoms, --(CH.sub.2).sub.n --NR.sup.7 R.sup.8, --(CH.sub.2).sub.n --CO.sub.2 R.sup.2, halo, nitro, cyano, ##STR33## --(CH.sub.2).sub.n --OR.sup.11, --(CH.sub.2).sub.n --SO.sub.3 R.sup.11, --(CH.sub.2).sub.n --SO.sub.2 --(C.sub.1 -C.sub.6)alkyl, or --(CH.sub.2).sub.n --SO.sub.2 NR.sup.7 R.sup.8 ;
• R.sup.5 is hydrogen or (C.sub.1 -C.sub.6)alkyl optionally substituted with one or more halo atoms;
• each R.sup.7 and each R.sup.8 is selected independently of any other R.sup.7 or R.sup.8 in the same molecule, and is selected from the group consisting of hydrogen, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.8)alkoxy (C.sub.1 -C.sub.6)alkyl and (C.sub.3 -C.sub.8)cycloalkyl, or R.sup.7 and R.sup.8, when attached to the same nitrogen atom, together with the nitrogen to which they are attached, form a saturated heterocyclic ring having from 3 to 5 carbon atoms wherein one of said carbon atoms may optionally be replaced by oxygen, nitrogen or sulfur;
• R.sup.11, wherever it occurs, is selected independently from any other R.sup.11 in the same molecule and is hydrogen or (C.sub.1 -C.sub.6) alkyl optionally substituted with one or more halo atoms;
• n is an integer from zero to six;
• X is a direct link, oxygen or sulfur;
• Y is oxygen, nitrogen or sulfur;
• and
• Z is carbon or nitrogen;
• with the proviso that:
• (i) when Y is oxygen or sulfur, R.sup.3 is absent, and (ii) when Z is nitrogen, R.sup.5 is absent;
• or a pharmaceutically acceptable prodrug of said compound or a pharmaceutically acceptable salt of said compound or prodrug thereof, that is effective in treating said condition.