| 摘要 |
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. |
