Novel compounds as cannabinoid receptor ligands and uses thereof

A method of treating a disorder selected from the group consisting of inflammatory disorders, immune disorders, neurological disorders, cancers of the immune system, respiratory disorders, and cardiovascular disorders in a mammal in need of such treatment, comprising administering to the mammal a therapeutically effective amount of a compound having formula (I)

• or a pharmaceutically acceptable salt, prodrug, salt of a prodrug, or a combination thereof, wherein
• R1 is alkyl, alkenyl, alkoxyalkyl, alkoxyalkoxyalkyl, alkoxycarbonylalkyl, alkynyl, arylalkoxyalkyl, arylalkyl, aryloxyalkyl, carboxyalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkoxyalkyl, heteroarylalkyl, heteroaryloxyalkyl, heterocycle, heterocyclealkyl, heterocycleoxyalkyl, hydroxyalkyl, or RaRbN-alkylene-;
• R2 and R3 are the same or different, and are each independently hydrogen, alkoxy, alkoxycarbonyl, alkoxycarbonylalkyl, azidoalkyl, alkyl, alkylcarbonyl, alkylsulfonyl, aryl, arylalkyl, arylalkenyl, cyano, cycloalkyl, cycloalkenyl, halo, haloalkyl, heteroaryl, heterocycle, —(CRjRk)n—ORp, —C(O)H, RcRdN—, RcRdN-alkylene-, ReRfNC(O)—, or R8-R7;
• or
• R2 and R3, together with the carbon atoms to which they are attached, form a 4-, 5-, 6-, or 7-membered monocyclic ring, optionally fused to a benzo or a monocyclic heteroaryl, said monocyclic ring contains zero, one, or two additional double bonds, zero or one oxygen atom, and zero or one nitrogen atom as ring atoms;
• two non-adjacent atoms of said monocyclic ring can be optionally linked by an alkenylene bridge of 2, 3, or 4 carbon atoms, or optionally linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms, said monocyclic ring is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of oxo, alkyl, alkylsulfonyl, halo, —OH, —O(alkyl), and haloalkyl;
• two substituents on the same carbon atom of said monocyclic ring, together with the carbon atom to which they are attached, optionally form a 3-, 4-, 5-, or 6-membered monocyclic cycloalkyl ring, wherein the monocyclic cycloalkyl ring is optionally substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from the group consisting of alkyl and haloalkyl;
• with the proviso that when R1 is cycloalkylalkyl, and L2 is a single bond, then R2 and R3 are not both alkyl;
• R4 is a bridged cycloalkyl or a bridged heterocycle;
• optionally substituted with 1, 2, 3, 4, 5, or 6 substituents selected from the group consisting of alkyl, —ORp, —NRcRd, oxo, halo, haloalkyl, carboxy and ═CH2;
• R7 and R8, are independently aryl, cycloalkyl, cycloalkenyl, heteroaryl, or heterocycle;
• Ra and Rb are each independently hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, aryl, arylalkyl, arylcarbonyl, arylsulfonyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heteroarylcarbonyl, heteroarylsulfonyl, heterocycle, heterocyclealkyl, heterocyclecarbonyl or heterocyclesulfonyl;
• Rc and Rd, at each occurrence, are each independently hydrogen, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl or arylalkyl;
• Re and Rf, at each occurrence, are each independently hydrogen or alkyl;
• L2 is a single bond, alkylene, —NRg— or —NRg-alkylene- wherein the alkylene moiety is attached to R4 of formula (I);
• Rg is hydrogen or alkyl,
• The aryl, cycloalkyl, cycloalkenyl, heterocycle, and heteroaryl moieties, as substituents or part of a substituent, represented by R1, R2, R3, Ra, Rb, Rc, Rd, R7, and R8, are each independently unsubstituted or substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from the group consisting of alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkoxyalkyl, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyloxy, alkylsulfinyl, alkylsulfinylalkyl, alkylsulfonyl, alkylsulfonylalkyl, alkylthio, alkylthioalkyl, alkynyl, carboxy, carboxyalkyl, cyano, cyanoalkyl, formyl, formylalkyl, halo, haloalkyl, haloalkoxy, oxo, hydroxy, hydroxyalkyl, —SH, —NO2, —NZ1Z2, and (NZ3Z4)carbonyl;
• Z1 and Z2 are each independently hydrogen, alkyl, haloalkyl, alkylcarbonyl, or formyl;
• Z3 and Z4 are each independently hydrogen, alkyl, or haloalkyl;
• Rj and Rk, at each occurrence, are each independently hydrogen, halo, alkyl or haloalkyl;
• Rp, at each occurrence, is independently hydrogen, alkyl, or haloalkyl;
• and
• n is 1, 2, 3, 4, or 5.