Patent IL-101382-A (IL)
Title: Piperidinyl-n- alkyl- carboxylates, process for their preparation and pharmaceutical compositions containing them
IPC: C07D401/06
Filed: 1992-03-26
Abstract: Peripheral opioid antagonist compounds of the formula OR1CH3R2 NR3O (CH2)nCH-C-A wherein: R1 is hydrogen or C1-C5 alkyl; R2 is hydrogen, C1-C5 alkyl or C2-C6 alkenyl; R3 is hydrogen, C1-C10 alkenyl, phenyl, cycloalkyl, C5-C8 cycloalkenyl, cycloalkyl- substituted C1-C3 alkyl, C5-C8 cycloalkenyl-substituted C1-C3 alkyl or phenyl-substituted C1-C3 alkyl; A is OR4 or NR5R6; wherein: R4 is hydrogen, C1-C10 alkyl C2-C10 alkenyl, cycloalkyl, C5-C8 cycloalkenyl, cycloalkyl-substituted C1-C3 alkyl, C5-C8 cycloalkenyl-substituted C1-C3 alkyl or phenyl-substituted C1-C3 alkyl; R5 is hydrogen or C1-C3 alkyl; R6 is hydrogen, C1-C10 alkyl, C3-C10 alkenyl, cycloalkyl, phenyl, cycloalkyl-substituted C1-C3 alkyl, C5-C8 cycloalkenyl, C5-C8 cycloalkenyl-substituted C1-C3 alkyl, phenyl-substituted C1-C3 alkyl, or (CH2)q-B; or R5 and R6 are each CH2 which together with N form a 4- to 6-membered heterocyclic ring wherein: B is ONN CR5O ,CWorNR7R8; wherein: R7 is hydrogen or C1-C3 alkyl; R8 is hydrogen, C1-C10 alkyl, C3-C10 alkenyl, cycloalkyl-substituted C1-C3 alkyl, cycloalkyl, C5-C8 cycloalkenyl, C5-C8 cycloalkenyl-substituted C1-C3 alkyl, phenyl or phenyl-substituted C1-C3 alkyl; or R7 and R8 are each CH2 which together with N form a 4 - to 6-membered heterocyclic ring; W is OR9, NR10R11, or OE; wherein; R9 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, cycloalkyl, C5-C8 cycloalkenyl, cycloalkyl-substituted C1-C3 alkyl, C5-C8 cycloalkenyl-substituted C1-C3 alkyl or phenyl-substituted C1-C3 alkyl; R10 is hydrogen or C1-C3 alkyl; R11 is hydrogen, C1-C10 alkyl, C3-C10 alkenyl, phenyl, cycloalkyl, C5-C8 cycloalkenyl, cycloalkyl-substituted C1-C3 alkyl, phenyl- substituted C1-C3 alkyl, O or (CH2)mCY; or R10 and R11 are each CH2 which together with N form a 4 - to 6-membered heterocyclic ring; O E is (CH2) m C-D, H3COO -CH2OO , or O -R12-OCR13 wherein: R12 is C1-C3 alkyl substituted methylene, R13 is C1-C10 alkyl; D is OR14 or NR15R16; wherein: R14 is hydrogen, C1-C10 alkenyl, cycloalkyl, C5-C8 cycloalkenyl, cycloalkyl-substituted C1-C3 alkyl, or C5-C8 cycloalkenyl-substituted C1-C3 alkyl or phenyl-substituted C1-C3 alkyl; R15 is hydrogen, C1-C10 alkyl, C3-C10 alkenyl, phenyl, phenyl-substituted C1-C3 alkyl, cycloalkyl, C5-C8 cycloalkenyl, cycloalkyl-substituted C1-C3 alkyl or C5-C8 cycloalkenyl-substituted C1-C3 alkyl; R16 is hydrogen or C1-C3 alkyl; R15 and R16 are each CH2 which together with N form a 4 - to 6-membered heterocyclic ring; Y is OR17 or NR18R19; wherein: R17 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, cycloalkyl, C5-C8 cycloalkenyl, cycloalkyl-substituted C1-C3 alkyl, C5-C8 cycloalkenyl-substituted C1-C3 alkyl, or phenyl-substituted C1-C3 alkyl; R18 is hydrogen or C1-C3 alkyl; R19 is hydrogen, C1-C10 alkyl, C3-C10 alkenyl, phenyl, cycloalkyl, C5-C8 cycloalkenyl, cycloalkyl-substituted C1-C3 alkyl, C5-C8 cycloalkenyl-substituted C1-C3 alkyl, or phenyl-substituted C1-C3 alkyl;or R18 and R19 are each CH2 which together with N form a 4 - to 6-membered heterocyclic ring; n is 0-4; q is 1-4; m is 1-4; or pharmaceutically acceptable salts thereof.