Analgesic compounds and methods of use
Provided herein, inter alia, are methods and compositions for achieving an analgesic effect in subjects in need thereof.
1. A method of producing sexually dimorphic analgesia in a male subject in need thereof, the method comprising administering to the male subject a therapeutically effective amount of a compound having the formula:
or a pharmaceutically acceptable salt thereof; wherein R 4 is hydrogen or methyl; R 5 is —C(O)-L 1 -R 3 ; L 1 is a bond, —CH 2 —, —CH 2 CH 2 —, or —CH 2 CH 2 CH 2 —; and R 3 is (i) an unsubstituted 5-membered heterocyloalkyl; (ii) an unsubstituted 6-membered heterocycloalkyl; (iii) a 5-membered heterocyloalkyl substituted with one or two substituents selected from the group consisting of ═O, halogen, —OH, —NH 2 , —SH, —C(O)OH, —C(O)NH 2 , —CF 3 , —CCl 3 , —CN, —N 3 , an unsubstituted C 1 -C 8 alkyl, and benzyl; or (iv) a 6-membered heterocycloalkyl.
2. The method of claim 1 , wherein R 3 is (i) an unsubstituted 5-membered heterocyloalkyl containing one nitrogen heteroatom; (ii) an unsubstituted 6-membered heterocycloalkyl containing one nitrogen heteroatom; (iii) a 5-membered heterocyloalkyl containing one nitrogen heteroatom and one or two substituents selected from the group consisting of ═O, halogen, —OH, —NH 2 , —SH, —C(O)OH, —C(O)NH 2 , —CF 3 , —CCl 3 , —CN, —N 3 , an unsubstituted C 1 -C 8 alkyl, and a benzyl; or (iv) a 6-membered heterocycloalkyl containing one nitrogen heteroatom and one or two substituents selected from the group consisting of ═O, halogen, —OH, —NH 2 , —SH, —C(O)OH, —C(O)NH 2 , —CF 3 , —CCl 3 , —CN, —N 3 , an unsubstituted C 1 -C 8 alkyl, a benzyl, and an indene moiety.
3. The method of claim 1 , wherein R 3 is a 5-membered heterocyloalkyl containing one nitrogen heteroatom and one or two substituents selected from the group consisting of ═O, —OH, —NH 2 , benzyl, methyl, and ethyl; or a 6-membered heterocycloalkyl containing one nitrogen heteroatom and one or two substituents selected from the group consisting of ═O, —OH, —NH 2 , methyl, ethyl, benzyl, and an indene moiety.
4. The method of claim 1 , wherein the compound is of the formula:
5. The method of claim 4 , wherein the compound is of the formula:
6. The method of claim 5 , wherein the compound is of the formula: