Therapeutic compounds and methods of use thereof

A method of treating a disease or condition in a mammal selected from the group consisting of pain, depression, cardiovascular diseases, respiratory diseases, and psychiatric diseases, and combinations thereof, wherein the method comprises administering to the mammal in need thereof a therapeutically effective amount of a compound of Formula I:

• or a salt thereof;
• wherein
• each RAA is independently selected from the group consisting of F, Cl, Br, I, —CN, —ORA1, —(XRA)-(6-12 membered aryl), —(XRA)-(5-12 membered heteroaryl), and —RA2, wherein said 6-12 membered aryl and 5-12 membered heteroaryl of RAA is optionally substituted with from 1 to 5 substitutents independently selected from the group consisting of F, Cl, Br, I, C1-4 alkyl, C1-4 haloalkyl, and C1-4(halo)alkoxy;
• RA1 is selected from the group consisting of hydrogen, C1-8 alkyl, C2-8 alkenyl, C1-8 haloalkyl, C3-8 cycloalkyl, phenyl and benzyl;
• RA2 is selected from the group consisting of C1-8 alkyl that is optionally substituted with one or more substituents selected from oxo (═O), fluoro, amino, C1-4 alkylamino and di(C1-4alkyl)amino;
• XKA is selected from the group consisting of absent, —C(═O)—, and C1-4 alkylene;
• wherein any C1-4 alkylene of XRA is optionally substituted with 1 to 3 substituents selected from the group consisting of C1-4 alkyl, C1-4 haloalkyl, and phenyl that is optionally substituted with 1 to 5 substitutents selected from, F, Cl, Br, I, —NH2, —OH, —CN, —NO2, C1-4 alkyl, C1-4 haloalkyl, C1-4alkoxy, C1-4(halo)alkoxy, C1-4 alkylamino and C1-4 dialkylamino;
• n is 0, 1, 2, 3, 4, 5, 6, 7, or 8;
• ring “A” is a 3-15 membered carbocyclyl, a 6-12 membered aryl, a 5-12 membered heteroaryl, or a 3-15 membered heterocyclyl;
• X1 and X2 are each independently selected from the group consisting of absent, —S—, —O— and —N(RX)— wherein Rx is H, C1-8 alkyl, or C1-8 haloalkyl, and wherein if the subscript m is 0 then one of X1 or X2 is absent;
• L is C1-6 alkylene, wherein L is optionally substituted with from 1 to 3 substituents independently selected from the group consisting of C1-4 alkyl, C1-4 alkoxy, halo, oxo (═O), and C1-4 haloalkyl;
• wherein any two substituents attached to the same atom on L are optionally combined to form a 3- to 5-membered carbocyclic ring;
• m is 0 or 1;
• R2 is selected from the group consisting of F, Cl, Br, I, and C3-8 cycloalkyl;
• R4 is selected from the group consisting of F, Cl, Br, I, and C1-8 haloalkyl;
• and R5 are each independently selected from the group consisting of H, F, Cl, Br, I, —CN, C1-8 alkyl, C3-8 cycloalkyl, C1-8 haloalkyl and C1-8 alkoxy;
• X is selected from the group consisting of O, S, S═O, SO2, N(RN), C═O, CH2, and C═S, wherein RN is selected from the group consisting of H, C1-6 alkyl and acyl;
• ring “B” is selected from the group consisting of cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl, wherein ring B is optionally substituted with one or more groups independently selected from C1-4 alkyl;
• and
• R6 is hydrogen or C1-6 alkyl.