Compounds as cannabinoid receptor ligands

A compound according to formula (I), or a pharmaceutically acceptable salt, solvate, salt of a solvate, prodrug, salt of a prodrug, or a combination thereof

• wherein
• R1 is aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl;
• wherein each ring is independently substituted by one Rx group and optionally further substituted with 1, 2, 3, or 4 Ry group(s);
• Rx is —C(═NORf)Ra, —(CR1aR1b)q1-A1, alkenyl, or alkynyl;
• wherein the alkenyl and the alkynyl are substituted with one or two A2 groups;
• each Ry is independently G1d, alkyl, alkenyl, alkynyl, halogen, haloalkyl, ═N—CN, ═N—ORf, NO2, —CN, oxo, —ORf, —OC(O)Rf, —OC(O)N(Rf)2, —S(O)2Re, —S(O)2N(Rf)2, —C(O)Rf, —C(O)ORf, —C(O)N(Rf)2, —N(Rf)2, —N(Rf)C(O)Rf, —N(Rf)S(O)2Re, —N(Rf)C(O)O(Re), —N(Rf)C(O)N(Rf)2, —(CR1cR1d)q3—ORf, —(CR1cR1d)q3—OC(O)Rf, —(CR1cR1d)q3—OC(O)N(Rf)2, —(CR1cR1d)q3—S(O)2Re, —(CR1cR1d)q3—S(O)2N(Rf)2, —(CR1cR1d)q3—C(O)Rf, —(CR1cR1d)q3—C(O)ORf, —(CR1cR1d)q3—C(O)N(Rf)2, —(CR1cR1d)q3—N(Rf)2, —(CR1cR1d)q3—N(Rf)C(O)Rf, —(CR1cR1d)q3—N(Rf)S(O)2Re, —(CR1cR1d)q3—N(Rf)C(O)O(Re), —(CR1cR1d)q3—N(Rf)C(O)N(Rf)2, or —(CR1cR1d)q3—CN;
• A1 is —ORa, —OC(O)Ra, —OC(O)N(Rb)(Rc), —N(Rb)(Rk), —C(O)O(Ra), —C(O)Ra, —S(O)2Rd, —S(O)Rd, —SRd, —C(O)N(Rb)(Rc), —C(S)N(Rb)(Rc), —S(O)2N(Rb)(Rc), —C(═NORf)Ra, —CN, —N(Rc)C(O)Ra, —N(Rc)C(O)ORd, —N(Rc)S(O)2Rd, —N(Rc)C(O)N(Rb)(Rc), —N(Rc)S(O)2N(Rb)(Rc), G1a or G1b;
• each occurrence of A2 is independently —ORa, —OC(O)Ra, —OC(O)N(Rb)(Rc), —N(Rb)(Rk′), —C(O)O(Ra), —C(O)Ra, —S(O)2Rd, —S(O)Rd, —SRd, —C(O)N(Rb)(Rc), —C(S)N(Rb)(Rc), —S(O)2N(Rb)(Rc), —C(═NORf)Ra, —CN, —N(Rc)C(O)Ra, —N(Rc)C(O)ORd, —N(Rc)S(O)2Rd, —N(Rc)C(O)N(Rb)(Rc), —N(Rc)S(O)2N(Rb)(Rc), or G1c;
• G1a is a 4-, 5-, 6-, or 7-membered monocyclic heterocycle having zero double bond and one or two heteroatoms in the ring, wherein each ring is substituted with 1, 2, or 3 substituents independently selected from the group consisting of oxo, alkyl, alkenyl, alkynyl, haloalkyl, —OH, alkoxy, —C(O)O(alkyl), and hydroxyalkyl;
• G1b is optionally substituted cycloalkyl or optionally substituted cycloalkenyl;
• G1c is cycloalkyl, cycloalkenyl, aryl, heterocycle, or heteroaryl;
• each ring as represented by G1b and G1c is optionally substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from the group consisting of oxo, alkyl, alkenyl, alkynyl, halogen, haloalkyl, ═N—CN, —C(═NORf)Ra, ═N—ORf, —CN, NO2, oxo, —ORa, —OC(O)Ra, —OC(O)N(Rb)(Rc), —S(O)Rd, —S(O)2Rd, —S(O)2N(Rb)(Rc), —C(O)Ra, —C(O)ORa, —C(O)N(Rb)(Rc), —N(Rb)(Rc), —N(Rc)C(O)Ra, —N(Rc)S(O)2Rd, —N(Rc)C(O)O(Ra), —N(Rc)S(O)2N(Rb)(Rc), —N(Rc)C(O)N(Rb)(Rc), —(CR1cR1d)q3—ORa, —(CR1cR1d)q3—OC(O)Ra, —(CR1cR1d)q3—OC(O)N(Rb)(Rc), —(CR1cR1d)q3—S(O)Rd, —(CR1cR1d)q3—S(O)2Rd, —(CR1cR1d)q3—S(O)2N(Rb)(Rc), —(CR1cR1d)q3—C(O)Ra, —(CR1cR1d)q3—C(O)ORa, —(CR1cR1d)q3—C(O)N(Rb)(Rc), —(CR1cR1d)q3—N(Rb)(Rc), —(CR1cR1d)q3—N(Rc)C(O)Ra, —(CR1cR1d)q3—N(Rc)S(O)2Rd, —(CR1cR1d)q3—N(Rc)C(O)O(Ra), —(CR1cR1d)q3—N(Rc)S(O)2N(Rb)(Rc), —(CR1cR1d)q3—N(Rc)C(O)N(Rb)(Rc), and —(CR1cR1d)q3—CN;
• Ra and Rc, at each occurrence, are each independently hydrogen, alkyl, haloalkyl, —(CR1aR1b)q3-A3, G1d, or —(CR1aR1b)q3-G1d;
• Rb, at each occurrence, is independently hydrogen, alkyl, haloalkyl, alkoxyalkyl, monocyclic cycloalkyl, —(CR1cR1d)q3-(monocyclic cycloalkyl), or haloalkoxyalkyl;
• Rd, at each occurrence, is independently alkyl, haloalkyl, —(CR1aR1b)q3-A3, G1d, or —(CR1aR1b)q3-G1d;
• G1d, at each occurrence, is independently a monocyclic heterocycle, a monocyclic heteroaryl, a phenyl, a monocyclic cycloalkyl, or a monocyclic cycloalkenyl;
• each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of —N(Rh)2, —CN, oxo, alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, and —OH;
• each occurrence of A3 is independently C(O)Rh, —S(O)2Re, —C(O)N(Rh)2, —C(S)N(Rh)2, —S(O)2N(Rh)2, —C(═NORh)Rh, —N(Rh)C(O)Rh, —N(Rh)C(O)ORe, —N(Rh)S(O)2Re, —N(Rh)C(O)N(Rh)2, —N(Rh)S(O)2N(Rh)2, —CN, —ORh, or —N(Rh)2;
• Re, at each occurrence, is independently C1-C4 alkyl, C1-C4 haloalkyl, monocyclic cycloalkyl, monocyclic heterocycle, or —(CR1cR1d)q3-(monocyclic cycloalkyl);
• Rf, at each occurrence, is independently hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, monocyclic heterocycle, monocyclic cycloalkyl, or —(CR1cR1d)q3-(monocyclic cycloalkyl);
• Rk is haloalkyl, —(CR1aR1b)q3-A3, G1d, or —(CR1aR1b)q3-G1d;
• Rk′ is hydrogen, alkyl, haloalkyl, —(CR1aR1b)q3-A3, G1d, or —(CR1aR1b)q3-G1d;
• Rh, at each occurrence, is independently hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, monocyclic heterocycle, monocyclic cycloalkyl, or —(CR1cR1d)q3-(monocyclic cycloalkyl);
• Ring A represents formula (a), (b), (c), or (d)
• R21, R22, R23, and R24 are each independently alkyl, alkenyl, alkynyl, haloalkyl, —(CR2aR2b)q4—OH, —(CR2aR2b)q4—O-alkyl, —(CR2aR2b)q4—O-haloalkyl, —(CR2aR2b)q4—O-G2a, —(CR2aR2b)q4—O—(CR2cR2d)q3-G2a, —(CR2aR2b)q5—C(O)—Ra, —(CR2aR2b)q5—C(O)O(Ra), —(CR2aR2b)q5—C(═N—ORf)Ra, —(CR2aR2b)q5—SO2—Rd, —(CR2aR2b)q5-G2b, —(CR2aR2b)q5—C(O)N(Rb)(Rc), or —(CR2aR2b)q5—CN;
• each occurrence of G2a is independently cycloalkyl, heterocycle, aryl, or heteroaryl;
• G2b is a monocyclic cycloalkyl, monocyclic cycloalkenyl, thienyl, or phenyl;
• each of which is optionally fused with a benzo, a monocyclic cycloalkyl, a monocyclic cycloalkenyl, a monocyclic heterocycle, or a monocyclic heteroaryl;
• G2a and G2b, at each occurrence, are each independently unsubstituted or substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from the group consisting of oxo, alkyl, halogen, —OH, alkoxy, haloalkoxy, and haloalkyl;
• R3, R4, R5, R6, R7, R8, R9, R11, and R12 are each independently G3, hydrogen, alkyl, alkenyl, alkynyl, —NO2, —CN, halogen, —ORh, —N(Rh)2, —C(O)Rh, —C(O)O(Rh), haloalkyl, —(CR3aR3b)q6—ORh, —(CR3aR3b)q6—N(Rh)2, —(CR3aR3b)q6—C(O)Rh, or —(CR3aR3b)q6—C(O)O(Rh);
• G3, at each occurrence, is independently cycloalkyl, cycloalkenyl, aryl, heterocycle or heteroaryl, wherein each G3 is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from the group consisting of C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, halogen, C1-C4 haloalkyl, ═N—CN, ═N—ORh, —CN, oxo, —ORh, —OC(O)Rh, —OC(O)N(Rh)2, —S(O)2Re, —S(O)2N(Rh)2, —C(O)Rh, —C(O)ORh, —C(O)N(Rh)2, —N(Rh)2, —N(Rh)C(O)Rh, —N(Rh)S(O)2Rc, —N(Rh)C(O)O(Rc), and —N(Rh)C(O)N(Rh)2;
• R1a, at each occurrence, is independently hydrogen, halogen, C1-C4 alkyl, or C1-C4 haloalkyl;
• R1b, at each occurrence, is independently hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl, —ORh, —N(Rh)2, —N(Rh)C(O)Rh, —N(Rh)C(O)ORe, or —N(Rh)S(O)2Re;
• R1c, R1d, R2a, R2b, R2c, R2d, R3a and R3b, at each occurrence, are each independently hydrogen, halogen, C1-C4 alkyl, or C1-C4 haloalkyl;
• X1 and X2 are independently O, S, or N(R10) wherein R10 is alkyl, alkoxyalkyl, haloalkoxyalkyl, or haloalkyl;
• q1 and q3, at each occurrence, are each independently 1, 2, 3, or 4;
• q4, at each occurrence, is independently 2, 3, 4, or 5;
• q5 and q6, at each occurrence, are each independently 1, 2, 3, 4, 5, or 6;
• and
• the monocyclic cycloalkyl and the monocyclic heterocycle, as a substituent or as part of a substituent, of Rb, Re, Rf, and Rh, are each independently unsubstituted or substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of oxo, C1-C4 alkyl, halogen, —OH, C1-C4 alkoxy, C1-C4 haloalkoxy, and C1-C4 haloalkyl;
• with the proviso that when Rx is —(CR1aR1b)q1-A1, R1a and R1b are each independently hydrogen or alkyl, and A1 is ORa wherein Ra is G1d, then G1d is other than phenyl;
• and
• with the further proviso that when Rx is —(CR1aR1b)q1-A1, R1a and R1b are each independently hydrogen or alkyl, and A1 is OC(O)Ra, then Ra is other than alkyl.