Substituted cycloalkanes
AssigneeThe Upjohn Company
InventorsMoses W. McMillan, Jacob Szmuszkovicz
Life of this patent
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Abstract
[2-Amino(substituted cycloaliphatic)]benzeneacetamide and benzamide compounds, e.g., trans-3,4-dichloro-N-methyl-N-[7-(1-pyrrolidinyl)-1,4-dioxaspiro[4.5]dec-8 -yl]benzeneacetamide, have useful analgesic activity and low abuse or physical dependence liability, or are useful as chemical intermediates for producing such analgesic compounds. Processes for their preparation are disclosed. Pharmaceutical compositions and methods of use are also disclosed.
Claims26
A compound of the formula ##STR9## wherein p and n are each full number integers of from 1 to 3, so that the resulting cycloaliphatic ring has five to seven carbon atoms;
- the wavy line bond (.about.) between the nitrogen in the 2-position and the cycloaliphatic ring carbon indicates the bond can be either cis- or trans- with respect to each substituent on the cycloaliphatic ring;
- q is 0 or 1;
- X and Y are independently selected from the group consisting of hydrogen, a halogen having an atomic number of from 9 to 35, trifluoromethyl, nitro, methoxy, hydroxy, azido, C.sub.1 to C.sub.3 -alkyl, phenyl, methanesulfonyl, cyano, amino, C.sub.1 to C.sub.3 -alkoxycarbonyl, C.sub.1 to C.sub.3 -alkanoyloxy, C.sub.1 to C.sub.3 -carboxacylamino [(-NHC(O)R.sub.6)];
- R is hydrogen or C.sub.1 to C.sub.3 -alkyl;
- R.sub.1 and R.sub.2, taken separately, are hydrogen, C.sub.1 to C.sub.3 -alkyl, allyl,
- R.sub.1 and R.sub.2, taken together with the nitrogen to which they are bonded, complete a ring selected from the group consisting of azetidinyl, pyrrolidinyl, and piperidinyl;
- R.sub.3, taken separately, is hydrogen, hydroxy,--OR.sub.5 or OC(.dbd.O)R.sub.6 ;
- R.sub.4, taken separately, is hydrogen;
- R.sub.3 and R.sub.4, taken together, are selected from the group consisting of --ECH.sub.2 CH.sub.2 E--;
- =E,
- [--N.about.OH], .dbd.N.about.OH and
- [-N.about.OC(O)CH.sub.3 ].dbd.N.about.OC(O)CH.sub.3 ;
- wherein each E is bivalent sulfur or oxygen, and R.sub.3 and R.sub.4 cannot both be hydrogen at the same time;
- R.sub.5 is C.sub.1 to C.sub.3 -alkyl;
- R.sub.6 is hydrogen or C.sub.1 to C.sub.2 -alkyl;
- or an acid addition salt thereof, provided that when R is methyl, R.sub.1 and R.sub.2, taken together with the nitrogen to which they are bonded, form a pyrrolidinyl, X and Y are each chlorine in the 3- and 4-positions of the phenyl ring, p is 1, n is 2, q is 1, E is oxygen, R.sub.4 is hydrogen, then R.sub.3 cannot be acetoxy and a 5-alpha orientation (on the same side of the cycloaliphatic ring as the amide nitrogen).
A composition of claim 27 wherein the compound of Formula I is trans-3,4-dichloro-N-methyl-N[7-(1-pyrrolidinyl)-1,4-dioxaspiro[4.5]dec-8- yl]-benzeneacetamide, or a pharmacologically acceptable salt thereof.
A method of claim 29 wherein the compound is trans-3,4-dichloro-N-methyl-N-[7-(1-pyrrolidinyl)-1,4-dioxaspiro[4.5]dec-8 -yl]benzeneacetamide or a pharmacologically acceptable salt thereof.
Dependencies are inferred from the claim text.