Novel compounds as cannabinoid receptor ligands

A compound having formula (I)

• or pharmaceutically acceptable salts, prodrugs, salts of prodrugs, or combinations thereof, wherein
• L is C═O, C═S, S(O)2, or C═NCN;
• R1 is alkyl, alkenyl, alkynyl, —(CRaRb)m—OH, —(CRaRb)m—O(alkyl), —(CRaRb)m—CN, haloalkyl, or G1;
• R2 is alkyl, alkenyl, alkynyl, G1, —C(RZb)═NO(R1e), —O(RZa), —N(RZ1)(RZ2b), —(CRaRb)m—N3, —(CRaRb)m—CN, haloalkyl, —(CRaRb)m—O(RZa), —(CRaRb)m—S(RZb), —(CRaRb)m—C(O)O(RZb), (CRaRb)m—C(O)N(RZ1)(RZ2a), —(CRaRb)m—SO2N(RZ1)(RZ2a), —(CRaRe)m—C(O)(RZb), —(CRaRb)m—SO2(RZd), —SO2(RZd), —(CRaRb)m—C(RZb)═NO(RZ1), —(CRaRb)m—N(RZ1)(RZ2b), or —(CRaRb)m-G1;
• R3 is hydrogen, alkyl, halogen, —CN, -G2, haloalkyl, or —(CRaRb)m-G2;
• R4 is alkyl, alkenyl, alkynyl, —(CRaRb), —CN, —(CRaRb)m—OH, —(CRaRb)n—O(alkyl), haloalkyl, G2, or —(CRaRb)m-G2;
• or
• R2 and R3, or R3 and R4, together with the atoms to which they are attached, form a five-, six-, or seven-membered monocyclic ring containing zero or one additional double bond, zero or one additional heteroatom selected from O, S, N, or N(H), each said ring is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents (R21) selected from the group consisting of oxo, alkyl, alkenyl, alkynyl, halogen, —CN, —O(R1a), —C(O)OH, —C(O)O(alkyl), —C(O)(R1a), —N(RZ3)(R3a), —N(R3a)C(O)R1a, —N(R3a)C(O)O(R1a), —N(R3a)C(O)N(RZ3)(R3a), —N(R3a)S(O)2(R2a), —N(R3a)S(O)2N(RZ3)(R3a), —SO2(R2a), —C(O)N(RZ3)(R3a), —S(O)2N(RZ3)(R3a), —(CR1gR1h)u-G2, —(CR1gR1h)u—CN, —(CR1gR1h)u—O(R1a), and haloalkyl, two adjacent or non-adjacent atoms of each of said rings are optionally linked by an alkylene bridge of one, two, three, or four carbon atoms;
• and two substituents (R21) on the same carbon atom, together with said carbon atom, optionally form a 3-6 membered monocyclic ring containing 0, 1, or 2 heteroatoms selected from O, S, or N(H);
• RZa, at each occurrence, is independently hydrogen, alkyl, haloalkyl, —(CRcRd)p—O(alkyl), G1, —(CRcRd)q—CN, or —(CRcRd)q-G1;
• RZb, at each occurrence, is independently hydrogen, alkyl, haloalkyl, G1, or —(CRcRd)q-G1;
• RZ1, at each occurrence, is independently hydrogen, alkyl, or haloalkyl;
• Z2a, at each occurrence, is independently hydrogen, alkyl, haloalkyl, G1, or —(CRcRd)q-G1, or
• R2b, at each occurrence, is independently hydrogen, alkyl, haloalkyl, G1, —C(O)RZc, —C(O)ORZc, —C(O)N(RZ1)(RZc), —S(O)2RZd, —S(O)2N(RZ1)(RZc), or —(CRcRd)q-G1,
• RZc, at each occurrence, is independently hydrogen, alkyl, haloalkyl, G1, or —(CReRf)t-G1;
• RZd, at each occurrence, is independently alkyl, haloalkyl, G1, or —(CReRf)t-G1;
• G1, at each occurrence, is aryl, heteroaryl, cycloalkyl, cycloalkenyl, or heterocycle, wherein each G1 is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halogen, —CN, oxo, -G2, —NO2, —C(RZ3)═N—O(R1a), —ORa, —O—(CR1gR1h)u—CN, —OC(O)R1a, —OC(O)N(RZ3)(R3a), —O—(CR1gR1h)u—CON(RZ3)(R3a), —O—(CR1gR1h)u—SO2N(RZ3)(R3a), —SR1a, —S(O)2R2a, —S(O)2N(RZ3)(R3a), —C(O)R1a, —C(O)OR1a, —C(O)N(RZ3)(R3a), —N(RZ3)(R3a), —N(RZ3)C(O)R1a, —N(RZ3)S(O)2R2a, —N(RZ3)C(O)O(R1a), —N(RZ3)C(O)N(RZ3)(R3a), (CR1gR1h)u—NO2, —(CR1gR1h)u—OR1a, —(CR1gR1h)u—OC(O)R1a, —(CR1gR1h)u—C(O)N(RZ3)(R3a), —(CR1gR1h)u—SR1a, —(CR1gR1h)u—S(O)2R2a, —(CR1gR1h)u—S(O)2N(RZ3)(R3a), —(CR1gR1h)u—C(O)R1a, —(CR1gR1h)u—C(O)OR1a, —(CR1gR1h)u—C(O)N(RZ3)(R3a), —(CR1gR1h)u—N(RZ3)(R3a), —(CR1gR1h)u—N(RZ3)C(O)R1a, —(CR1gR1h)u—N(RZ3)S(O)2R2a, —(CR1gR1h)u—N(RZ3)C(O)O(R1a), —(CR1gR1h)u—N(RZ3)C(O)N(RZ3)(R3a), —(CR1gR1h)u-G2, —(CR1gR1h)u—CN, and haloalkyl;
• R1a and R3a, at each occurrence, is independently hydrogen, alkyl, haloalkyl, G2, or —(CRkRx)v-G2;
• R2a, at each occurrence, is independently alkyl, haloalkyl, G2, or —(CRkRx)v-G2;
• G2, at each occurrence, is aryl, heteroaryl, cycloalkyl, cycloalkenyl, or heterocycle, wherein each G2 is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halogen, —CN, oxo, —NO2, —OR1b, —OC(O)R1b, —OC(O)N(RZ4)(R3b), —SR1b, —S(O)2R2b, —S(O)2N(RZ4)(R3b), —C(O)R1b, —C(O)OR1b, —C(O)N(RZ4)(R3b), —N(RZ4)(R3b), —N(RZ4)C(O)R1b, —N(RZ4)C(O)O(R1b), —N(RZ4)C(O)N(RZ4)(R3b), (CR2gR2h)w—NO2, —(CR2gR2h)w—OR1b, —(CR2gR2h)w—OC(O)R1b, —(CR2gR2h)w—OC(O)N(RZ4)(R3b), —(CR2gR2h)w—SR1b, —(CR2gR2h)w—S(O)R2b, —(CR2gR2h)wS(O)2N(RZ4)(R3b), —(CR2gR2h)w—C(O)R1b, —(CR2gR2h)w—C(O)OR1b, —(CR2gR2h)w—C(O)N(RZ4)(R3b), —(CR2gR2h)w—N(RZ4)(R3b), —(CR2gR2h)w—N(RZ4)C(O)R1b, —(CR2gR2h)w—N(RZ4)C(O)O(R1b), —(CR2gR2h)w—N(RZ4)C(O)N(RZ4)(R3b), —(CR2gR2h)w—CN, and haloalkyl;
• m, q, t, u, v, and w, at each occurrence, are each independently 1, 2, 3, 4, or 5;
• n and p, at each occurrence, are each independently 2, 3, 4, or 5;
• R1b and R3b, at each occurrence, is independently hydrogen, alkyl, or haloalkyl;
• R2b, at each occurrence, is independently alkyl or haloalkyl;
• Ra, Rc, Rd, Re, Rf, R1g, R1h, R2g, R2h, Rk, and Rx, at each occurrence, are each independently hydrogen, halogen, alkyl, or haloalkyl;
• each occurrence of Rb is independently hydrogen, halogen, alkyl, haloalkyl, or OH;
• and
• RZ3 and RZ4, at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;
• with the proviso that the compound is other than
• 4-methyl-N-[(3Z)-1-phenyl-1,4,5,6-tetrahydro-3H-cyclopenta[c]isothiazol-3-ylidene]benzenesulfonamide;
• N-[(3Z)-1-cyclohexyl-4,5,6,7-tetrahydro-2,1-benzisothiazol-3(1H)-ylidene]-4-methylbenzenesulfonamide;
• or
• 4-methyl-N-[(3Z)-1-phenyl-4,5,6,7-tetrahydro-2,1-benzisothiazol-3(1H)-ylidene]benzenesulfonamide.