2-cycloalkyl resorcinol cannabinergic ligands

A compound of formula I or a pharmaceutically acceptable salt thereof, including all stereoisomers and enantiomers:

• wherein:
• R1 and R2 are each independently selected from the group consisting of:
• —H, —F, —Cl, —Br, —I, —OH, —SH, —NH2, —NO2, —CN, —CF3, —OC(O)CH3, —C(O)CH3, —C(O)CF3, —O-alkyl, OSi(alkyl)3, —S— alkyl, —NH-alkyl, —N(alkyl)z, —O—P(O)(OR)2, —O—P(O)(OH)(OR) (wherein R is selected from the group consisting of H and alkyl), —P(O)(OR)2, —P(O)(OH)(OR) (wherein R is selected from the group consisting of H and alkyl), —O-alkyl-COOR (wherein R is selected from the group consisting of H and alkyl), —O-alkyl-NR6R7, —O-alkyl-CONR6R7, —OC(O)—R (wherein R is selected from the group consisting of H and alkyl), —OC(O)—CH(OH)—CH2OH, —OC(O)—C(CH2OH)2—CH3, —OC(O)—CH2OH, —OC(O)-alkyl-COOH, —OC(O)—CH═CHCOOH, —OC(O)-alkyl-NR6R7, —OC(O)-alkyl-C(O)NR6R7, —OC(O)—O-alkyl-NR6R7, and —OC(O)—CH(NH2)—R8 (wherein R8 is selected from the group consisting of H, CH(OH)CH3 and alkyl-X1, and X1 is selected from the group consisting of:
• —H, —NHC(═NH)NH2, —C(O)NH2, —COOH, —SH, —SCH3, —OH, —NH2, and an aromatic, heteroaromatic or heterocyclic ring);
• R6 and R7 are each independently selected from the group consisting of:
• H and alkyl, or R6 and R7 together comprise part of a 3 to 7 membered saturated heterocyclic ring containing up to one additional heteroatom selected from the group consisting of N, O and S;
• R3 is selected from the group consisting of:
• -cycloalkyl-R9, -heterocyclic-R9, -adamantyl, -adamantyl-R9, and -heteroadamantyl-R9;
• R9 is selected from the group consisting of:
• —(CH2)j—R10, —(CH)j-A-(CH2)k—R10, and —(CH2)j-A-(CH2)k—B—R10;
• A and B are each independently selected from the group consisting of:
• —CH2—CH2—, —C≡C—, —CH═CH—, —O—, —S—, —NH—, —C(O)—, —C(O)O—, —OC(O)—, —C(O)NH—, —NHC(O)—, —S(O)—, —SO2—, —SO2NH—, —NHSO2—, —SO2O— and —OSO2—;
• R10 is selected from the group consisting of:
• —H, —F, —Cl, —Br, —I, —OH, —SH, —NH2, —CN, —N3, —NCS, —NCO, —SO2Cl, —SO2F, —SO2NH2, —C(O)NH2, —COOH, —NO2, —CHO, —CF3, —SO3H, —O—P(O)(OH)2, —Sn(alkyl)3, —Si(alkyl)3, —C≡CH, —CH═CH2, and an aromatic, heteroaromatic or heterocyclic ring;
• j is an integer from 0 to 8;
• k is an integer from 0 to 8;
• R4 is selected from the group consisting of:
• -alkyl-R11, and —C1-3alkyl-OC(O)-alkyl;
• R11 is selected from the group consisting of:
• —F, —Cl, —Br, —I, —OH, —SH, —NH2, —NH-alkyl, —N(alkyl)2, —CN, —N3, —NCS, —OC(O)CH3, —C(O)OCH3, —SO2NH2, —C(O)NH2, —COOH, —NO2, —CHO, —CF3, —Sn(alkyl)3, —Si(alkyl)3, —C≡CH, —CH═CH2, and an aromatic, heteroaromatic or heterocyclic ring;
• R5 is selected from the group consisting of:
• —H, -alkyl, -alkyl-R12, -alkenyl, -alkenyl-R12, -alkynyl and -alkynyl-R12;
• and
• R12 is selected from the group consisting of:
• —F, —Cl, —Br, —I, —OH, —SH, —NH2, —NH-alkyl, —N(alkyl)2, —CN, —N3, —NCS, —OC(O)CH3, —C(O)OCH3, —SO2NH2, —C(O)NH2, —COOH, —NO2, —CHO, —CF3, —Sn(alkyl)3, —Si(alkyl)3, —C≡CH, —CH═CH2, —(CH2)n-Q (wherein Q is selected from the group consisting of —F, —Cl, —Br, —I, —OH, and n is an integer from 1 to 5), and an aromatic, heteroaromatic or heterocyclic ring.