Patent IL-96821-A (IL)
Title: 3-aminopiperidine derivatives, related nitrogen containing heterocycles and pharmaceutical compositions containing them
Inventor: DESAI MANOJ C
IPC: A61K31/34
Filed: 1990-12-28
Abstract: Substance P antagonist compounds of the formula R1R7R1 YNR| NR2(I) AR5 wherein A is R8- (CH2)m and Y is (CH2) n wherein n is an R6 integer from 1 to 6, and wherein any one of the carbon-carbon single bonds in said (CH2) n may optionally be replaced by a carbon-carbon double bond, and wherein any one of the carbon atoms of said (CH2) n may optionally be substituted with R4, and wherein any one of the carbon atoms of said (CH2) n may optionally be substituted with R7; m is an integer from 0 to 8, and any one of the carbon-carbon single bonds of said (CH2) 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 (CH2) m may optionally be substituted with R8; R1 is hydrogen or (C1-C6) alkyl optionally substituted with hydroxy, alkoxy or fluoro and (C7-C8) alkyl optionally substituted with hydroxy, alkoxy or fluoro; R2 is a radical selected from hydrogen, (C1-C6) straight or branched alkyl, (C3-C7) cycloalkyl wherein one of the carbon atoms may optionally be replaced by nitrogen, oxygen or sulfur; aryl selected from phenyl, naphthyl and indanyl, heteroaryl selected from thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl and quinolyl; phenyl (C2-C6) alkyl, benzhydryl and benzyl, wherein each of said aryl and heteroaryl groups and the phenyl moieties of said benzyl, phenyl (C2-C6) alkyl and benzhydryl may optionally be substituted with one or more substituents independently selected from halo, nitro, (C1-C6) alkyl, (C1-C6) alkoxy, trifluoromethyl, amino, OO (C1-C6) alkylamino, (C1-C6) alkyl-O-C-, (C1-C6) alkyl-O-C- OO (C1-C6) alkyl-, (C1-C6) alkyl-C-O-, (C1-C6) alkyl-C- OO (C1-C6) alkyl-O-, (C1-C6) alkyl-C-, (C1-C6) alkyl-C- O (C1-C6) alkyl-, di-(C1-C6) alkylamino, -CNH- (C1-C6) alkyl, OOO (C1-C6) alkyl-C-NH-(C1-C6) alkyl-, NHCH and -NHC- (C1-C6) alkyl; and wherein one of the phenyl moieties of said benzhydryl may optionally be replaced by naphthyl, thienyl, furyl or pyridyl; R5 is hydrogen, phenyl or (C1-C6) alkyl; or R2 and R5, 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; R3 is aryl selected from phenyl, naphthyl and indanyl; heteroaryl selected from thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl and quinolyl; and cycloalkyl having 3 to 7 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 (C3-C7) cycloalkyl may optionally be substituted with one or two substituents, each of said substituents being independently selected from halo, nitro, (C1-C6) alkyl, (C1-C6) alkoxy, trifluoromethyl, amino, (C1-C6) alkylamino, OOO -CNH- (C1-C6) alkyl, (C1-C6) alkyl-C-NH- (C1-C6) alkyl, -NHCH and O NHC- (C1-C6) alkyl; and R4 and R7 are each independently selected from hydrogen, hydroxy, halo, amino, oxo (=O); nitrile, (C1-C6) alkylamino, di-(C1-C6) alkylamino, (C1-C6) alkoxy, OO (C1-C6) alkyl-O-C-, (C1-C6) alkyl-O-C- (C1-C6) alkyl-, hydroxy - (C1-C6) alkyl, (C1-C6) alkoxy - (C1-C6) alkyl, OO (C1-C6) alkyl-C-O-, (C1-C6) alkyl-C-(C1-C6) alkyl-O-, OO (C1-C6) alkyl-C-, (C1-C6) alkyl-C- (C1-C6) alkyl-, and the radicals set forth in the definition of R2, R6 is NHCR9, NHCH2R9, SO2R9 or one of the radicals set forth in any of the definitions of R2, R4 and R7; R8 is oximino (=NOH) or one of the radicals set forth in any of the definitions of R2, R4, and R7; R9 is (C1-C6) alkyl, hydrogen, phenyl, or phenyl (C1-C6) alkyl; with the proviso that (a) when m is o, R8 is absent, (b) neither R4, R6, R7, nor R8 can form, together with the carbon to which it is attached, a ring with R5, (c) when R4 and R7 are attached to the same carbon atom, then either each of R4 and R7 is independently selected from hydrogen, fluoro and (C1-C6) alkyl, or R4 and R7, together with the carbon to which they are attached, form a (C3-C6) saturated carbocyclic ring that forms a spiro compound with the nitrogen-containing ring to which they are attached, (d) when n is 2 and either R4 or R7 is 5-hydroxy (C1-C6) alkyl or 5- (C1-C6) alkoxy (C1-C6) - alkyl, then the other of R4 and R7 is hydrogen, (e) when n is 2, neither R4 nor R7 is 4-hydroxy (C1-C6) alkyl or 4-(C1-C6) alkoxy (C1-C6) alkyl, and (f) one of R2 and R5 must be other than hydrogen or unsubstituted (C1-C6) alkyl; or pharmaceutically acceptable acid addition salts thereof.