Beta-arrestin-biased cannabinoid CB1 receptor agonists and methods for making and using them

A compound having the Formula I:

• or a pharmaceutically acceptable salt thereof;
• wherein
• R1 is selected from the group consisting of halo, cyano, nitro, and acetyl;
• R2 is selected from the group consisting of C1-12 alkyl, C0-4 alkyl-C3-8 cycloalkyl, and C0-4 alkyl-C6-10 aryl,
• R3 is selected from the group consisting of C3-C8 cycloalkyl and 4- to 8-membered heterocyclyl;
• W is selected from the group consisting of N and CR1a, wherein R1a is selected from the group consisting of H and R1;
• X is selected from the group consisting of O, C═O, and NR4, wherein R4 is selected from the group consisting of H and C1-6 alkyl;
• Y1, Y2, and Y3 are independently selected from the group consisting of N and CH;
• Z is selected from the group consisting of O, CH2, and NR4, wherein R4 is selected from the group consisting of H and C1-6 alkyl;
• subscript t is 0 when W is CR1a and R1a is R1;
• subscript t is 1 when W is N or when W is CR1a and R1a is H;
• and
• L is selected from the group consisting of
• wherein
• R5, R6, R7, and R8 are independently selected from the group consisting of H and OH, provided that at least one of R5 and R6 is H and at least one of R7 and R8 is H, or
• one of R5 and R6 is taken together with one of R7 and R8 to form a 5- to 6-membered saturated carbocyclic or heterocyclic group, or
• R5 and R7 are absent and R6 and R8 are taken together to form a 5- to 6-membered unsaturated carbocyclic or heterocyclic group, and
• R9 and R10 are independently selected from the group consisting of H and OH, provided that at least of R9 and R10 is H.