Endocannabinoid ligands and related analogs

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

• wherein:
• A2 is selected from
• i is an integer from 1 to about 5,
• R1 and R2 are independently selected from —H, -D, —Cl, —Br, —F, —OH, -Me, —CHF2, —CH2F, —CF3,
• R′ is selected from —H, -D and —CH3,
• R″ is -alkyl,
• B2 is selected from
• j is an integer from 1 to about 4,
• Z1, Z2, independently selected from -D, —F, -Me, —CF3,
• n is an integer from 1 to about 7,
• Y2 is selected from -Alkyl, —H, -D, —F, —I, —Cl, —Br, —CF3, —CN, —NCS, —N3—NO2, —SO2F, —ONO2, —OH, —SH, —NH2, —(NH)-Alkyl, —N(Alkyl)2, -heterocyclic ring, -carbocyclic ring, -Ph, —OPh, —SPh, —SOPh, —SO2Ph and
• unless otherwise specifically denoted, each of the aforementioned groups is connected to the main structure from any possible position given that it is fulfilling the valency requirements,
• R4 is selected from —F, —CN, —CF3,
• Z is —NH—, —CH2NH—, —NHCONH—, —COO—, —COOCH2— or —CH2—.

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

• wherein:
• A3 is selected from
• R1 and R2 are independently selected from —H, -D, —Cl, —Br, —F, —OH, -Me, —CHF2, —CH2F, —CF3,
• R′ is selected from —H, -D and —CH3,
• B3 is selected from
• j is an integer from 1 to about 4,
• Z1, Z2, independently selected from —H, -D, —F, -Me, —CF3,
• D1, D2, D3 and D4 are each independently selected from —CH2—, —CF2—, —CD2- and
• provided that at least one of D1 or D2 or D3 or D4 in general formula I is a chiral group selected from
• m is an integer from 0 to about 6.

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

• wherein:
• A4 is selected from
• j is an integer from 1 to about 5,
• R1 and R2 are independently selected from —H, -D, —Cl, —Br, —F, —OH, -Me, —CHF2, —CH2F, —CF3,
• R′ is selected from —HC, -D and —CH3,
• R″ is -alkyl,
• B4 is selected from
• j is an integer from 1 to about 4,
• Z1, Z2, independently selected from —H, -D, —F, -Me, —CF3,
• D1, D2, D3 and D4 are each independently selected from —CH2—, —CF2—, —CD2- and
• provided that at least one of D1 or D2 or D3 or D4 is a cycloalkyl group selected from:
• Y4 is selected from -Alkyl, —H, -D, —F, -L, —Cl, Br, —CF3, —CN, —NCS, —N3—NO2, —SO2F, —ONO2, —OH, —SH, —NH2, —(NH)-Alkyl, —N(Alkyl)2, -heterocyclic ring, -carbocyclic ring, -Ph, —OPh, —SPh, —SOPh, —SO2Ph and
• unless otherwise specifically denoted, each of the aforementioned groups is connected to the main structure from any possible position given that it is fulfilling the valency requirements,
• R4 is selected from —F, —CN, —CF3,
• Z is —NH—, —CH2NH—, —NHCONH—, —COO—, —COOCH2— or —CH2—.

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

• wherein:
• A5 is selected from
• R1, R2 are independently selected from —H, -D, —Cl, —Br, —F, —OH, -Me, —CHF2, —CH2F, —CF3,
• R′ is selected from —H, -D and —CH3,
• R″ is -alkyl,
• i is an integer from 1 to about 5,
• B5 is selected from
• j is an integer from 1 to about 4,
• Z1, Z2, independently selected from —H, -D, —F, -Me, —CF3,
• W1, W2, W3 and W4 are independently selected from ═, ≡ or a π electron system selected from the groups shown below
• provided that the general structure V encompasses at least one of the aforementioned π electron systems and each of the π electron systems is connected to the main structure in any possible position given that it is fulfilling the valency requirements,
• R4 is selected from -D, —F, —CF3, —CN,
• X is selected from CH2, NH, O, S,
• D1, D2, D3 and D4 are independently selected from —CH2—, —CF2—, —CD2- and
• n is an integer from 1 to about 7,
• Y5 is selected from -Alkyl, —H, -D, —F, —I, —Cl, Br, —CF3, —CN, —NCS, —N3—NO2, —SO2F, —ONO2, —OH, —SH, —NH2, —(NH)-Alkyl, —N(Alkyl)2, -heterocyclic ring, -carbocyclic ring, -Ph, —OPh, —SPh, —SOPh, —SO2Ph and
• unless otherwise specifically denoted, each of the aforementioned groups is connected to the main structure from any possible position given that it is fulfilling the valency requirements,
• R4 is selected from —F, —CN, —CF3,
• Z is —NH—, —CH2NH—, —NHCONH—, —COO—, —COOCH2— or —CH2—.