Bicyclic cannabinoids

A compound of formula Ia below, including physiologically acceptable salts, diastereomers, enantiomers, double bond isomers, or mixtures thereof;

• wherein:
• Y is selected from >C═O or >C═CY7Y8, including all isomers,
• Y7 and Y8 are each independently selected from H, alkyl, alkenyl, CN, OH, alkoxy or —(CH2)n—NR10R11,
• R10 and R11 are each independently selected from H, alkyl, hydroxyalkyl, or R10 and R11 together comprise part of a 3 to 7 membered saturated heterocyclic ring containing up to one additional heteroatom selected from N, O and S,
• n is an integer from 0 to about 4, wherein when an integer is 0 the structural portion modified by that integer is absent and the adjacent subunits are directly connected;
• R1 and R2 are each independently selected from H, OH, NH2, NO2, CN, OCOCH3, OC(O)CH═CHCOOH, halogen, alkyl, —O-alkyl, acyl, aroyl, benzoyl, substituted benzoyl, phenacyl, substituted phenacyl, —O-alkyl-aryl, —O-alkyl-NR10R11, —O-alkyl-COOR (where R is selected from H or alkyl), —O-alkyl-CONR10R11,——N(alkyl)2, —CO(alkyl)X or —OCO(alkyl)X or OCO(alkenyl)X(where X is selected from H, COOH, dialkylamino, a cyclic amine, a carbocyclic ring, a heterocyclic ring, an aromatic ring or a heteroaromatic ring), —O—P(O)(OR)2 or —O—P(O)(OH)(OR) (where R is selected from H or alkyl), —P(O)(OR)2 (where R is selected from H or alkyl), —P(O)(OH)(OR) (where R is selected from H or alkyl) or —OC(O)—CH(NH2)—R16 (where R16 is selected from H, CH(OH)CH3 or alkyl-X3 and X3 is selected from:
• H, —NH—C(═NH)NH2, C(O)NH2, COOH, SH, SCH3, OH, NH2, a substituted or unsubstituted aromatic ring, a substituted or unsubstituted heteroaromatic ring, a substituted or unsubstituted heterocyclic ring,
• R10 and R11 are each independently selected from H, alkyl, hydroxyalkyl or R10 and R11 together comprise part of a 3 to 7 membered saturated heterocyclic ring containing up to one additional heteroatom selected from N, O and S;
• and
• R3 is
• wherein R5 is selected from H, halogen, CN, CF3, N3, COOH, NH2, N(CH3)2, ⊕N(CH3)3, Sn(alkyl)3, phenyl, OH, NCS, NCO, NO2, CHO, SO3H, SO2Cl, SO2F, PO3H2, C(O)CF3, SH, —CH═CH2, —C≡CH, NH(alkyl), N(alkyl)2, O-aryl, alkoxy, thioalkoxy, sulfonamide, COOR (where R is selected from H or alkyl), a substituted or unsubstituted carbocylic ring, a substituted or unsubstituted heterocyclic ring, a substituted or unsubstituted aromatic ring, a substituted or unsubstituted heteroaromatic ring, a polycarbocyclic ring structure having 2 to about 5 rings, a polyheterocyclic ring structure having 2 to about 5 rings or CONR10R11 (where R10and R11 are each independently selected from H, alkyl, hydroxyalkyl, or R10 and R11 together comprise part of a 5 or 6 membered saturated heterocyclic ring containing up to one additional heteroatom selected from N, O and S),
• n is an integer from 0 to about 7, wherein when an integer is 0 the structural portion modified by that integer is absent and the adjacent subunits are directly connected;
• with the following provisos:
• if Y is C═O, and R1 and R2 are both OH, then R3 cannot be C(CH3)2(CH2)nCH3 (where n is an integer from 3-5).

A compound of formula Ib below, including physiologically acceptable salts, diastereomers, enantiomers, double bond isomers, or mixtures thereof;

• wherein:
• Y is selected from >C═O, >CH—(CH2)f—Y1—(CH2)g—Y2, >C═N—Y3, >CH—NY4Y5 or >CH—(CH2)h—Y6, including all isomers,
• Y1 is independently selected from O, C(O)O or CH2,
• Y2 is independently selected from H, I, CN, CF3, N3, NCS or NCO,
• Y3 is independently selected from OH, NH2, C1-C4 alkoxy, C1-C4 alkyl, —(CH2)n—NR10R11, —(CH2)n—CO2R (where R comprises H or alkyl), —O—(CH2)n—NR10R11, —O—(CH2)n—CO2R (where R comprises H or alkyl) or —O—(CH2)n—CONR10R11,
• Y4 is independently selected from H, OH, C1-C4 alkoxy or C1-C4 alkyl,
• Y5 is independently selected from H, OH, C1-C4 alkoxy or C1-C4 alkyl, wherein Y4 and Y5 cannot both be OH and wherein Y4 and Y5 cannot both be C1-C4 alkoxy,
• Y6 is independently selected from I, CN, SO2Cl, SO2F, COalkyl, CF3, COfluoroalkyl, N3, NCS or NCO,
• R10 and R11 are each independently selected from hydroxyalkyl, or R10 and R11 together comprise part of a 3 to 7 membered saturated heterocyclic ring containing one additional heteroatom selected from N, O and S,
• f comprises an integer from 0 to about 5,
• g comprises an integer from 0 to about 5,
• h comprises an integer from 0 to about 5,
• n comprises an integer from 0 to about 4, wherein when an integer is 0 the structural portion modified by that integer is absent and the adjacent subunits are directly connected,
• R1 and R2 are each independently selected from OH, OCH3, NO2, CN, OCOCH3, aroyl, benzoyl, substituted benzoyl, phenacyl, substituted phenacyl, —O-alkyl-aryl, —O-alkyl-NR10R11, —O-alkyl-CONR10R11, —CO(alkyl)X or —OCO(alkyl)X(where X is selected from a cyclic amine, a carbocyclic ring, a heterocyclic ring, an aromatic ring or a heteroaromatic ring), —OC(O)—CH(NH2)—R (where R comprises H or CH(OH)CH3) or alkyl-X (where X is selected from H, —NH—C(═NH)NH2, C(O)NH2, COOH, SH, SCH3, OH, NH2, a substituted or unsubstituted aromatic ring, a substituted or unsubstituted heteroaromatic ring, a substituted or unsubstituted heterocyclic ring),
• R10 and R11 are each independently selected from hydroxyalkyl, or R10 and R11 together comprise part of a 3 to 7 membered saturated heterocyclic ring containing one additional heteroatom selected from N, O and S;
• and
• R3 is selected from the following structures:
• wherein each Z is independently selected from CH2, S, O, NH, N(CH3), SO or SO2,
• D is selected from a heterocyclic ring, an adamantyl ring, an heteroadamantyl ring or any above ring optionally substituted by R4 in any possible position with the proviso that ring D can not be bonded to R4 from the 1′ position,
• L is selected from a cycloalkyl ring, a heterocyclic ring, a heteroaromatic ring, an adamantyl ring, a heteroadamantyl ring or any above ring optionally substituted by R4 in any possible position,
• R4 is —(CH2)j-A-(CH2)k—R5,
• A is selected from —CH2—CH2—, —CH═CH—, —C≡C—, O, S, SO, SO2 or NH,
• R5 is selected from H, halogen, CN, CF3, N3, COOH, NH2, N(CH3)2, ⊕N(CH3)3, Sn(alkyl)3, phenyl, pyrrolidine ring, piperidine ring, morpholine ring, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, NCS, NCO, SO3H, SO2Cl, SO2F, PO3H2, C(O)CF3, —O-aryl, sulfonamide, a carbocylic ring, a heterocyclic ring, a heteroaromatic ring, a polycarbocyclic ring structure having 2 to about 5 rings, a polyheterocyclic ring structure having 2 to about 5 rings or CONR10R11 (where R10 and R11 are each independently selected from hydroxyalkyl, or R10 and R11 together comprise part of a 5 or 6 membered saturated heterocyclic ring containing one additional heteroatom selected from N, O and S),
• n is an integer from 0 to about 3,
• j is an integer from 0 to about 7,
• k is an integer from 0 to about 7, wherein when an integer is 0 the structural portion modified by that integer is absent and the adjacent subunits are directly connected,
• R6 and R7 are each independently selected from H or CH3,
• R8 is selected from —(CH2)j—C≡C—(CH2)k—R5 or —(CH2)j—CH═CH—(CH2)k—R5,
• R5 is selected from H, halogen, CN, CF3, N3, COOH, NH2, N(CH3)2, ⊕N(CH3)3, Sn(alkyl)3, phenyl, pyrrolidine ring, piperidine ring, morpholine ring, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, NCS, NCO, SO3H, SO2Cl, SO2F, PO3H2, C(O)CF3, —O-aryl, sulfonamide, a carbocylic ring, a heterocyclic ring, a heteroaromatic ring, a polycarbocyclic ring structure having 2 to about 5 rings, a polyheterocyclic ring structure having 2 to about 5 rings or CONR10R11 (where R10 and R11 are each independently selected from hydroxyalkyl, or R10 and R11 together comprise part of a 5 or 6 membered saturated heterocyclic ring containing one additional heteroatom selected from N, O and S),
• j is an integer from 0 to about 7,
• k is an integer from 0 to about 7, wherein when an integer is 0 the structural portion modified by that integer is absent and the adjacent subunits are directly connected,
• Q is selected from O, S, NH or N(R18) (where R18 is selected from SO2-aryl, alkyl-R5, aryl-R5 or heteroaryl-R5),
• R17 is selected from alkyl-R5, aryl-R5 or heteroaryl-R5 with the proviso that R5 cannot be hydrogen;
• with the following proviso:
• if Y is C═O, and R1 and R2 are both OH, then R3 cannot be structure Ib 4, where R6 and R7 are both H and R8 is (CH2)j—CH═CH—(CH2)k—R5 where R5 is H and the sum of j and k is equal to 4-9.