Piperidines promote release of growth hormone

A compound of the Formula Ib:

• ##STR132## wherein:
• R.sup.1 is selected from the group consisting of:
• ##STR133## or their regioisomers where not specified;
• R.sup.2 is selected from the group consisting of:
• hydrogen, --C.sub.1 -C.sub.6 alkyl, --C.sub.3 -C.sub.7 cycloalkyl, and --CH.sub.2 -phenyl, wherein the alkyl or the cyloalkyl is unsubstituted or substituted with hydroxyl, C.sub.1 -C.sub.3 alkoxy, thioalkyl, --C(O)OR.sup.2a, and wherein, if two --C.sub.1 -C.sub.6 alkyl groups are present on one atom, the groups may be optionally joined to form a C.sub.3 -C.sub.8 cyclic ring being selected from the group consisting of pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine;
• R.sub.2a is hydrogen, or C.sub.1 -C.sub.4 alkyl;
• B is selected from:
• ##STR134## R.sup.3 is selected from:
• hydrogen or phenyl, wherein the phenyl is substituted in the ortho position by a substituent selected from the group consisting of:
• C.sub.1 -C.sub.6 alkyl, halogen, --OR.sup.2, --(CH.sub.2).sub.r OR.sup.6, --(CH.sub.2).sub.r N(R.sup.2)(R.sup.6), --(CH.sub.2).sub.r (R.sup.6), --(CH.sub.2).sub.r C(O)OR.sup.2, --(CH.sub.2).sub.r C(O)OR.sup.6, --(CH.sub.2).sub.r C(O)R.sup.2, --(CH.sub.2).sub.r C(O)R.sup.6, --(CH.sub.2).sub.r C(O)N(R.sup.2)(R.sup.2), --(CH.sub.2).sub.r C(O)N(R.sup.2)(R.sup.6), --(CH.sub.2).sub.r SO.sub.2 N(R.sup.2)(R.sup.6), --(CH.sub.2).sub.r SO.sub.2 N(R.sup.2)(R.sup.2), --(CH.sub.2).sub.r S(O).sub.m R.sup.6, and --(CH.sub.2).sub.r S(O).sub.m R.sup.2 ;
• R.sup.3a and R.sup.3b are independently selected from:
• hydrogen, --C.sub.1 -C.sub.6 alkyl and halogen;
• E is selected from:
• ##STR135## which is optionally substituted with one or more substituent(s) selected from:
• halo, hydroxy, --N(R.sup.2)(R.sup.2a), C.sub.1 -C.sub.6 alkyl and C.sub.1 -C.sub.6 alkoxy;
• R.sup.4 and R.sup.5 are independently selected from hydrogen, C.sub.1 -C.sub.6 alkyl, and substituted C.sub.1 -C.sub.6 alkyl where the substituents are selected from halo, hydroxy, phenyl, and C.sub.1 -C.sub.6 alkoxycarbonyl;
• or R.sup.5 and R.sup.4 may be taken together to form --(CH.sub.2).sub.d -L.sub.a (CH.sub.2).sub.e - where L.sub.a is --C(R.sup.2).sub.2 --, --O--, --S(O).sub.m -- or --N(R.sup.2)--, d and e are independently 1 to 3 and R.sup.2 is as defined above;
• R.sup.4a and R.sup.4b are independently selected from:
• hydrogen, C.sub.1 -C.sub.6 alkyl, or substituted C.sub.1 -C.sub.6 alkyl where the substituents are selected from:
• imidazolyl, naphthyl, phenyl, indolyl, and p-hydroxyphenyl;
• R.sup.6 is selected from:
• hydrogen, C.sub.1 -C.sub.6 alkyl, (CH.sub.2).sub.v phenyl, and (CH.sub.2).sub.v heteroaryl, wherein the (CH.sub.2).sub.v and alkyl groups may be optionally substituted by --O(R.sup.2), --S(O).sub.m R.sup.2, --C(O)OR.sup.2, --C(O)N(R.sup.2)(R.sup.2), --SO.sub.2 N(R.sup.2)(R.sup.2), or --N(R.sup.2)C(O)N(R.sup.2)(R.sup.2), wherein the phenyl group is optionally substituted with C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, amino, or hydroxyl and wherein the heteroaryl group is selected from:
• pyridyl, 1H-tetrazolyl, triazolyl, oxadiazolyl, pyrazolyl, thiadiazolyl, and benzimidazol-2-yl, which is optionally substituted with C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, amino, or hydroxyl;
• X is selected from the group consisting of:
• hydrogen, ##STR136## and further selected from the following group of heterocyclic substituents:
• ##STR137## wherein the heterocycle substituent is optionally substituted with a substituent selected from:
• --N(R.sup.2)(R.sup.2), --O(R.sup.2), C.sub.1 -C.sub.3 alkyl, halogen, and trifluoromethyl;
• Y is selected from the group consisting of:
• hydrogen, ##STR138## or their regioisomers whereof where not specified;
• D is selected from:
• --N(R.sup.7)--, --S(O).sub.m --, --C(O)-- and --C(H)(R.sup.7)--, wherein R.sup.7 is selected from:
• --R.sup.2, --(CH.sub.2).sub.q aryl, --C(O)R.sup.2, --SO.sub.2 R.sup.2, --C(O)N(R.sup.2)(R.sup.2), --C(O)OR.sup.2, 1-H-tetrazol-5-yl, --SO.sub.2 N(R.sup.2)heteroaryl, --SO.sub.2 N(R.sup.2)(R.sup.2) and the (CH.sub.2).sub.q may be optionally substituted by C.sub.1 -C.sub.4 alkyl, and the R.sup.2 and aryl may be optionally further substituted with a substituent selected from:
• --OR.sup.2a, --C(O)OR.sup.2a, --C(O)N(R.sup.2a)(R.sup.2a), halogen, --C.sub.1 -C.sub.4 alkyl, and the heteroaryl is selected from the group consisting of:
• triazolyl, oxadiazolyl, 1H-tetrazolyl, and thiadiazolyl, which is optionally substituted with --OR.sup.2a, --C(O)OR.sup.2a, --C(O)N(CR.sup.2a)(R.sup.2a), halogen, or --C.sub.1 -C.sub.4 alkyl;
• m is 0, 1, or 2;
• q is 0, 1, 2, 3, or 4;
• r is 0, 1, 2, or 3;
• v is 0, 1, or 2;
• y is 0, 1, or 2;
• and pharmaceutically acceptable salts and individual diastereomers thereof.