3-Benzylamino-2-phenyl-piperidine derivatives as substance P receptor antagonists

A compound having the formula ##STR15## wherein m is an integer from 1 to 8, and any one of the carbon--carbon single bonds of (CH.sub.2).sub.m may optionally be replaced by a carbon--carbon double bond or a carbon--carbon triple bond, and any one of the carbon atoms of said (CH.sub.2).sub.m may optionally be substituted with R.sup.11 ;

• R.sup.1 is hydrogen or (C.sub.1 -C.sub.8) alkyl optionally substituted with hydroxy, alkoxy or fluoro;
• R.sup.3 is aryl selected from phenyl, indanyl and naphthyl;
• heteroaryl selected from benzothienyl, benzofuryl, thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, and quinolyl;
• or cycloalkyl having from three to seven carbon atoms, wherein one of said carbon atoms may optionally be replaced by nitrogen, oxygen or sulfur;
• wherein each of said aryl and heteroaryl groups may optionally be substituted with one or more substituents, and said (C.sub.3 -C.sub.7)cycloalkyl may optionally be substituted with one or two substituents, said substituents being independently selected from halo, nitro, (C.sub.1 -C.sub.10)alkyl optionally substituted with from one to three fluorine atoms, (C.sub.1 -C.sub.10)alkoxy optionally substituted with from one to three fluorine atoms, trifluoromethyl, amino, (C.sub.1 -C.sub.6)-alkylamino, di(C.sub.1 -C.sub.6) alkylamino, ##STR16## hydroxy(C.sub.1 -C.sub.6)alkyl, and (C.sub.1 -C.sub.6)alkoxy(C.sub.1 -C.sub.6)alkyl;
• R.sup.6 is a functionality selected from hydrogen, (C.sub.1 -C.sub.6)straight or branched alkyl, (C.sub.3 -C.sub.7)cycloalkyl wherein one of the carbon atoms may optionally be replaced by nitrogen, oxygen or sulfur;
• aryl selected from biphenyl, phenyl, indanyl and naphthyl;
• heteroaryl selected from benzothienyl, thienyl, furyl, benzofuryl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl and quinolyl;
• phenyl(C.sub.2 -C.sub.6)alkyl, benzhydryl and benzyl, wherein each of said aryl and heteroaryl groups and the phenyl moieties of said benzyl, phenyl(C.sub.2 -C.sub.6)alkyl and benzhydryl may optionally be substituted with one or more substituents independently selected from halo, nitro, (C.sub.1 -C.sub.10)alkyl optionally substituted with from one to three fluorine atoms, (C.sub.1 -C.sub.10)alkoxy optionally substituted with from one to three fluorine atoms, amino, hydroxy(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxy(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)-alkylamino, ##STR17## and wherein one of the phenyl moieties of said benzhydryl may optionally be replaced by naphthyl, thienyl, furyl or pyridyl;
• R.sup.7 is hydrogen, phenyl or (C.sub.1 -C.sub.6)alkyl;
• or R.sup.6 and R.sup.7, together with the carbon to which they are attached, form a saturated carbocyclic ring having from 3 to 7 carbon atoms wherein one of said carbon atoms may optionally be replaced by oxygen, nitrogen or sulfur;
• R.sup.8 may be attached to any atom of the nitrogen containing ring having an available bonding site and R.sup.9 may be attached to any carbon atom of the nitrogen containing ring having an available bonding site;
• R.sup.8 and R.sup.9 are independently selected from hydrogen, hydroxy, halo, amino, oxo (.dbd.O), cyano, hydroxy-(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxy-(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkylamino, di-(C.sub.1 -C.sub.6)alkylamino, (C.sub.1 -C.sub.6)alkoxy, ##STR18## and the functionalities set forth in the definition of R.sup.6 ;
• A is selected from the group consisting of CH.sub.2, nitrogen, oxygen, sulfur and carbonyl;
• G is nitrogen, oxygen or sulfur;
• R.sup.10 is a monocyclic or bicyclic heterocycle selected from the group consisting of pyrimidinyl, benzoxazolyl, 2,3-dihydro-3-oxobenzisosulfonazol-2-yl, succinimidyl or thienyl;
• R.sup.11 is oximino (.dbd.NOH) or one of the functionalities set forth in any of the definitions of R.sup.6, R.sup.8 and R.sup.9 ;
• and
• with the proviso that a) neither R.sup.8, R.sup.9, R.sup.10 nor R.sup.11 can form, together with the carbon to which it is attached, a ring with R.sup.7, (b) when R.sup.8 and R.sup.9 are attached to the same carbon atom, then either each of R.sup.8 and R.sup.9 is independently selected from hydrogen, fluoro, (C.sub.1 -C.sub.6)alkyl, hydroxy-(C.sub.1 -C.sub.6)alkyl, and (C.sub.1 -C.sub.6)alkoxy-(C.sub.1 -C.sub.6)alkyl;
• or R.sup.8 and R.sup.9, together with the carbon to which they are attached, form a (C.sub.3 -C.sub.6)saturated carbocyclic ring that forms a spiro compound with the nitrogen containing ring to which they are attached, (c) when A is nitrogen, sulfur or oxygen, m is greater than one, (d) when A is CH.sub.2 or carbonyl then R.sup.10 must be substituted or unsubstituted pyrimidinyl, benzoxazolyl, 2,3-dihydro-3-oxobenzisosulfonazol-2-yl, or succinimidyl;
• (e) when G is oxygen or sulfur then R.sup.1 is absent.