Adjacently substituted cycloalkane-amide analgesics

Claim 1

A compound of the formula wherein: R is hydrogen or C 1 to C 3 -alkyl; R 1 and R 2 , taken separately, are each hydrogen or C 1 to C 3 -alkyl; R 1 and R 2 , taken together with the nitrogen to which they are bonded, are azetidinyl, pyrrolidinyl or piperidinyl; R 3 , taken separately, is hydroxy, C 1 to C 2 -alkyloxy, or C 1 to C 3 -alkanoyloxy; R 4 , taken separately, is hydrogen when R 3 is hydroxy, C 1 to C 2 -alkyloxy,or C 1 to C 3 -alkanoyloxy; R 3 and R 4 , taken together, complete a moiety selected from the group, ═G (oxo or thioxo), --G--CH 2 CH 2 --G--, --G--CH 2 CH 2 CH 2 --G--, --G--CH 2 CH(CH 3 )CH 2 --G--, --G--CH 2 C(CH 3 ) 2 CH 2 --G--, wherein both G moieties in the same group are oxygen or bivalent sulfur, ═N˜OH, and ═N˜OC(═O)CH 3 , wherein each G is oxygen or bivalent sulfur; X and Y are independently selected from the group consisting of hydrogen, a halogen having an atomic number from 9 to 35, trifluoromethyl, nitro, methoxy, hydroxy, azido, C 1 to C 3 -alkyl, phenyl, methanesulfonyl, cyano, amino, C 1 to C 3 -alkoxycarbonyl, C 1 to C 3 -alkanoyloxy, C 1 to C 3 -carboxacylamino(--NHC(═O)R 6 , wherein R 6 is hydrogen or C 1 to C 2 -alkyl); p and n are whole number integers selected from the group zero, 2, 3, or 4 such that one of p and n is zero and the other of p and n is 2, 3, or 4; q is zero or 1; E is oxygen or bivalent sulfur; provided that when R is C 1 to C 3 -alkyl, R 1 and R 2 taken together with the nitrogen to which they are bonded complete a pyrrolidinyl ring, p is 3 and n is 0, q is 1, X and Y are chlorine in the 3 and 4 positions, R 3 is not hydroxy, C 1 to C 2 -alkoxy or C 1 to C 3 -alkanoyloxy;