Cannabinoid derivatives and methods for their preparation

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 and R4 are each independently selected from hydrogen, hydroxyl, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, alkoxy, aryl, aralkyl, heteroaryl, heteroaralkyl, nitro, cyano, —OR12, —C(═O)R12, —C(═O)OR12, —OC(═O)R12, —OC(═O)OR12, —NHC(═O)R12, —N(R13)(R14), —C(═O)N(R13)(R14), —OC(═O)N(R13)(R14), —NHC(═O)N(R13)(R14), and —C(═O)CHR15N(R13)(R14), each of which group may optionally be unsubstituted or substituted with one or more substituents,
• R2 is independently selected from —(C1-C6)alkyl, —C(═O)(C1-C6)alkyl, —C(═O)O(C1-C6)alkyl, —CN, —C(═O)NH(C1-C6)alkyl, —C(═O)N[(C1-C6)alkyl]2, —C(═O)CHR15NH(C1-C6)alkyl, and —C(═O)CHR15N[(C1-C6)alkyl]2;
• R3 is hydrogen;
• or
• R1 and R2, and/or R2 and R5, and/or R2 and R6, and/or R2 and R7, taken together with the carbon atoms to which each are attached, independently form a 4- to 8-membered ring, wherein 1 or 2 of the ring atoms independently are optionally replaced by —O—, —(C(═O)—, —(C(═O)O—, —NH—, —N(C1-C6)alkyl)-, —(C(═O)NH—, or —(C(═O)N(C1-C6)alkyl)-, and R′ and R4 are each independently selected from hydrogen, hydroxyl, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, alkoxy, aryl, aralkyl, heteroaryl, heteroaralkyl, nitro, cyano, —C(═O)R12, —C(═O)OR12, —OC(═O)R12, —OC(═O)OR12, —NHC(═O)R12, —N(R13)(R14), —C(═O)N(R13)(R14), —OC(═O)N(R13)(R14), —NHC(═O)N(R13)(R14), and —C(═O)CHR15N(R13)(R14), each of which group may optionally be unsubstituted or substituted with one or more substituents;
• R5, R5′, R6, R6′, R7, R7′, R8, R8′, R9, and R9′ are each independently selected from hydrogen, hydroxyl, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloallcyl, alkoxy, aryl, aralkyl, heteroaryl, heteroaralkyl, nitro, cyano, —OR12, —C(═O)R12, —C(═O)OR12, —OC(═O)R12, —OC(═O)OR12, —NHC(═O)R12, —N(R13)(R14), —C(═O)N(R13)(R14), —OC(═O)N(R13)(R14), —NIIC(═O)N(R13)(R14), and —C(═O)CHR15N(R13)(R14), each of which group may optionally be unsubstituted or substituted with one or more substituents, or
• R5, R5′, and/or R6, R6′, and/or R7, R7′, and/or R8, R8′, and/or R9, and R9′ each independently form C═O, C═S, or C═NH, or
• R5 and R6, or R5 and R6, or R6 and R7, or R6 and R8, or R7 and R8, or R7 and R9, or R8 and R9 taken together with the carbon atoms to which each are attached, independently form a 4- to 8-membered ring, wherein 1 or 2 of the ring atoms independently are optionally replaced by —O—, —(C(═O)—, —(C(═O)O—, —NH—, —N(C1-C6)alkyl)-, —(C(═O)NH—, or —(C(═O)N(C1-C6)alkyl)-, and the remainder of R5 and R6, or R5 and R7, or R6 and R7, or R6 and R8, or R7 and R8, or R7 and R9, or R8 and R9, are each independently selected from hydrogen, hydroxyl, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, alkoxy, aryl, aralkyl, heteroaryl, heteroaralkyl, nitro, cyano, —OR″, —C(═O)R12, —C(═O)OR12, —OC(C)R12, —OC(═O)OR12, —NHC(═O)R12, —N(R13)(R14), —C(═O)N(R13)(R14), —OC(═O)N(R13)(R″), —NHC(═O)N(RD)(R14), and —C(═O)CHR15N(R13)(R14), each of which group may optionally be unsubstituted or substituted with one or more substituents;
• A is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, alkoxy, aryl, aralkyl, heteroaryl, heteroaralkyl, 5- or 6-membered heterocyclic ring, 5- or 6-membered heteroaryl ring, and a 6-membered aryl ring, each of which group may be optionally unsubstituted or substituted with one or more substituents;
• R10 and R11 are each independently selected from hydrogen, hydroxyl, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, spiroalkyl, cycloalkenyl, heterocycloalkyl, alkoxy, aryl, aralkyl, heteroaryl, heteroaralkyl, nitro, cyano, —OR12, —C(═O)R12, —C(═O)OR12, —OC(═O)R12, —OC(═O)OR12, —NHC(═O)R12, —N(R13)(R14), —C(═O)N(R13)(R14), —OC(═O)(R13)(R14), —NHC(═O)N(R13)(R14), and —C(═O)CHR15N(R13)(R14), each of which group may optionally be unsubstituted or substituted with one or more substituents, or R10 and R11, taken together with the atom to which they are attached, independently form a substituted or unsubstituted 4 to 8 membered cyclic or heterocyclic ring, or a 5 membered heteroaryl ring, or a 6 membered aryl ring;
• m and n are each independently an integer ranging from 0 to 5;
• R12 is each independently selected from hydrogen, hydroxyl, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, alkoxy, aryl, aralkyl, heteroaryl, heteroaralkyl, nitro, cyano, —N(R13)(R14), —C(═O)N(R13)(R14), —OC(═O)N(R13)(R14), —NHC(═O)N(R13)(R14), and —C(═O)CHR15N(R13)(R14), each of which group may optionally be unsubstituted or substituted with one or more substituents;
• R13 and R14 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, and heteroaralkyl, or
• R13 and R14, taken together with the nitrogen atom to which they are attached, independently form a 4- to 8-membered heterocyclic ring wherein 1 or 2 of the ring atoms independently are optionally replaced by —O—, —S—, —S(═O)—, —S(═O)2—, —NH—, —N(alkyl)-, —N(C(═O)R12′)—, or —N(S(O)2—R12)—;
• and
• R15 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, and heteroaralkyl.