586058 Disclosed are benzomorphan compounds as represented by the general Formula I, wherein R1 and R2 are each independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -(CH2)n-O-(CH2)n-CH3, alkoxy, C(halo)3, CH(halo)2, CH2(halo), C(O)R6, -C(O)O-alkyl, and -(CH2)n-N(R7)2, each of which is optionally substituted by 1, 2, or 3 independently selected R8 groups； wherein at least one of R1 and R2 is alkyl which is substituted by one R8 group, wherein the R8 group is selected from cycloalkyl； R3 and R4 are each independently selected from H, alkyl, alkenyl, and alkynyl； R5 is selected from (a) H, OH, halo, C(halo)3, -CH(halo)2, and -CH2(halo)； or (b) alkyl, alkenyl, alkynyl, -(CH2)n-O-(CH2)n-CH3, alkoxy, each of which is optionally substituted with 1, 2, or 3 independently selected R8 groups； R6 is selected from -H, alkyl, alkenyl, alkynyl, and alkoxy； each R7 is independently selected from H, alkyl, alkenyl, and alkynyl； each R8 is independently selected from OH, halo, alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl , -CHO, CO2H, -C(halo)3, -CH(halo)2, CH2(halo), and -(CH2)n-O-(CH2)n-CH3； X- is an organic or inorganic anion； each n is independently selected from an integer from 0, 1, 2, 3, 4, 5, or 6 or a solvate or prodrug thereof, wherein the prodrugs are esters of compounds of formula (I). A representative compound includes 2'-hydroxy-2,5,9-trimethyl-2-cyclopropylmethyl-6,7-benzomorphanium-iodide / 3-cyclopropylmethyl-1,2,3,4,5,6-hexahydro-8-hydroxy-3,6,11-trimethyl-2,6-methano-3-benzazocinium iodide. Further disclosed is the use of a compound of Formula I as defined above for the manufacture of a pharmaceutical composition for the treatment of constipation.
