Cannabinoid derivatives
This disclosure relates to cannabinoid derivatives having the structure of formula (I), pharmaceutical compositions comprising them, and methods of using the cannabinoid derivatives in treating or preventing a diseases associated with a cannabinoid receptor in subject in need thereof, wherein the cannabinoid receptor is one or more of CB1, CB2, 5HT1A, 5HT2A, GPR18, GPR55, GPR119, TRPV1, TRPV2, PPARγ or a μ-opioid receptor.
1. A compound having structural formula:
or an enantiomer, diastereomer, racemate, or tautomer thereof, or a pharmaceutically acceptable salt, solvate or hydrate of the compound, enantiomer, diastereomer, racemate, or tautomer, wherein
the
moiety is
R 1 is hydrogen, halo, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, —CO 2 H, —(C 0 -C 4 alkyl)-C(O)O(C 1 -C 6 alkyl), —(C 0 -C 4 alkyl)-OC(O)O—(C 1 -C 6 alkyl), —OR 1a , —(C 1 -C 4 alkyl)OR 1a , —SR 1a , —(C 1 -C 4 alkyl)SR 1a , —NR 1b R 1c , —(C 1 -C 4 alkyl)NR 1b R 1c , —(C 1 -C 4 alkyl)C(O)NR 1b R 1c , —(C 0 -C 4 alkyl)-aryl, —(C 0 -C 4 alkyl)-heteroaryl, —(C 0 -C 4 alkyl)-cycloalkyl, —(C 0 -C 4 alkyl)-heterocycloalkyl, or oxo when attached to a ring of appropriate saturation, wherein
R 1a , R 1b , and R 1c are independently hydrogen, C 1 -C 4 alkyl, or —C(O)(C 1 -C 4 ) alkyl;
R 2 is hydrogen, halo, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, —CO 2 H, —(C 0 -C 4 alkyl)-C(O)O(C 1 -C 6 alkyl), —(C 0 -C 4 alkyl)-OC(O)O—(C 1 -C 6 alkyl), —OR 2a , —(C 1 -C 4 alkyl)OR 2a , —SR 2a , —(C 1 -C 4 alkyl)SR 2a , —NR 2b R 2c , —(C 1 -C 4 alkyl)NR 2b R 2c , —(C 1 -C 4 alkyl)C(O)NR 2b R 2c , —(C 0 -C 4 alkyl)-aryl, —(C 0 -C 4 alkyl)-heteroaryl, —(C 0 -C 4 alkyl)-cycloalkyl, —(C 0 -C 4 alkyl)-heterocycloalkyl, or oxo when attached to a ring of appropriate saturation, wherein
R 2a , R 2b , and R 2c are independently hydrogen, C 1 -C 4 alkyl, or —C(O)(C 1 -C 4 ) alkyl;
R 3 is C 1 -C 12 alkyl;
R 4 is
wherein
R 4a is C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, —OR 4c , —(C 1 -C 4 alkyl)OR 4c , —(C 1 -C 4 alkyl)-C(O)(C 1 -C 4 alkyl), —(C 0 -C 4 alkyl)-aryl, —(C 0 -C 4 alkyl)-heteroaryl, —(C 0 -C 4 alkyl)-cycloalkyl, —(C 0 -C 4 alkyl)-heterocycloalkyl, —NR 4d R 4e , or —(C 1 -C 4 alkyl)NR 4d R 4e , and
R 4b is C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, —CH 2 —(OCH 2 CH 2 ) 0-6 O(C 1 -C 8 alkyl), —(C 1 -C 4 alkyl)OR 4e , —(C 1 -C 4 alkyl)-C(O)(C 1 -C 4 alkyl), —(C 1 -C 4 alkyl)-C(O)O(R 4e ), —(C 0 -C 4 alkyl)-aryl, —(C 0 -C 4 alkyl)-heteroaryl, —(C 0 -C 4 alkyl)-cycloalkyl, —(C 0 -C 4 alkyl)-heterocycloalkyl, or —(C 1 -C 4 alkyl)NR 4d R 4e , wherein
R 4d is hydrogen, C 1 -C 6 alkyl, —(C 1 -C 4 alkyl)-C(O)(C 1 -C 4 alkyl), —(C 1 -C 4 alkyl)-C(O)O(R 4e ), —(C 1 -C 4 alkyl)-OC(O)(R 4e ), —(C 0 -C 4 alkyl)-aryl, —(C 0 -C 4 alkyl)-heteroaryl, —(C 0 -C 4 alkyl)-cycloalkyl, or —(C 0 -C 4 alkyl)-heterocycloalkyl,
R 4e is hydrogen or C 1 -C 4 alkyl, and
R 4c is hydrogen or C 1 -C 4 alkyl;
R 5 is hydrogen, C 1 -C 8 alkyl, —(C 1 -C 4 alkyl)-O—(C 0 -C 4 alkyl), —C(O)(C 1 -C 4 alkyl), —C(O)O(C 1 -C 4 alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 4 alkyl), —C(O)N(C 1 -C 4 alkyl) 2 , —(C 1 -C 4 alkyl)C(O)O(C 1 -C 4 alkyl), or —(C 1 -C 4 alkyl)OC(O)(C 1 -C 4 alkyl); and
R 6 is hydrogen or —OR 6a , wherein R 6a is hydrogen, C 1 -C 8 alkyl, —(C 1 -C 4 alkyl)-O—(C 0 -C 4 alkyl), —C(O)(C 1 -C 4 alkyl), —C(O)O(C 1 -C 4 alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 4 alkyl), —C(O)N(C 1 -C 4 alkyl) 2 , —(C 1 -C 4 alkyl)C(O)O(C 1 -C 4 alkyl), or —(C 1 -C 4 alkyl)OC(O)(C 1 -C 4 alkyl); wherein
each alkyl, alkenyl and alkynyl is unsubstituted, halogenated, substituted with one or two hydroxyl or C 1 -C 6 alkoxy groups, or substituted with one or two oxo groups;
each cycloalkyl has 3-10 ring carbons and is saturated or partially unsaturated, and optionally includes one or two fused cycloalkyl rings, each fused ring having 3-8 ring members, and is substituted with 0-6 R 7 ;
each heterocycloalkyl has 3-10 ring members and 1-3 heteroatoms where each is independently nitrogen, oxygen or sulfur and is saturated or partially unsaturated, and optionally includes one or two fused cycloalkyl rings, each having 3-8 ring members, and is substituted with 0-6 R 7 ;
each aryl is a phenyl or a naphthyl, and optionally includes one or two fused cycloalkyl or heterocycloalkyl rings, each fused cycloalkyl or heterocycloalkyl ring having 4-8 ring members, and is substituted with 0-5 R 8 ;
each heteroaryl is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms, where each is independently nitrogen, oxygen or sulfur or a 8-10 membered bicyclic heteroaryl having 1-5 heteroatoms where each is independently nitrogen, oxygen or sulfur, and optionally includes one or two fused cycloalkyl or heterocycloalkyl rings, each fused cycloalkyl or heterocycloalkyl ring having 4-8 ring members, and is substituted with 0-5 R 8 ,
in which
each R 7 is independently oxo, C 1 -C 4 alkyl, —Cl, —F, —Br, —CN, —SF 5 , —N 3 , nitro, —SR A , —S(O) 1-2 R A , —OR A , —(C 0 -C 3 alkyl)—OR B , —NR B R A , —C(O)R A , —C(O)NR B R A , —NR B C(O)R A , —C(S)NR B R A , —NR B C(S)R A , —CO 2 R A , —OC(O)R A , —C(O)SR A , —SC(O)R A , —C(S)OR A , —OC(S)R A , —C(S)SR A , —SC(S)R A , —S(O) 1-2 OR A , —OS(O) 1-2 R A , —S(O) 1-2 NR B R A , —NR B S(O) 1-2 R A , —OCO 2 R A , —OC(O)NR B R A , —NR B CO 2 R A , —NR B C(O)NR B R A , —SCO 2 R A , —OC(O)SR A , —SC(O)SR A , —SC(O)NR B R A , —NR B C(O)SR A , —OC(S)OR A , —OC(S)NR B R A , —NR B C(S)OR A , —NR B C(S)NR B R A , —SC(S)OR A , —OC(S)SR A , —SC(S)SR A , —SC(S)NR B R A , —NR B C(S)SR A , —NR B C(NR B )NR B R A , —NR B S(O) 1-2 NR B R A , phenyl, C 3 -C 8 cycloalkyl, a five to six-membered heteroaryl, or a five to six-membered heterocycloalkyl; and
each R 8 is independently optionally-substituted C 1 -C 4 alkyl, —Cl, —F, —Br, —CN, —SF 5 , —N 3 , nitro, —SR A , —S(O) 1-2 R A , —OR A , —(C 0 -C 3 alkyl)-OR B , —NR B R A , —C(O)R A , —C(O)NR B R A , —NR B C(O)R A , —C(S)NR B R A , —NR B C(S)R A , —CO 2 R A , —OC(O)R A , —SO 3 H,—C(O)SR A , —SC(O)R A , —C(S)OR A , —OC(S)R A , —C(S)SR A , —SC(S)R A , —S(O) 1-2 OR A , —OS(O) 1-2 R A , —S(O) 1-2 NR B R A , —NR B S(O) 1-2 R A , —OCO 2 R A , —OC(O)NR B R A , —NR B CO 2 R A , —NR B C(O)NR B R A , —SCO 2 R A , —OC(O)SR A , —SC(O)SR A , —SC(O)NR B R A , —NR B C(O)SR A , —OC(S)OR A , —OC(S)NR B R A , —NR B C(S)OR A , —NR B C(S)NR B R A , —SC(S)OR A , —OC(S)SR A , —SC(S)SR A , —SC(S)NR B R A , —NR B C(S)SR A , —NR B C(NR B )NR B R A , —NR B S(O) 1-2 NR B R A ; phenyl, C 3 -C 8 cycloalkyl, a five to six-membered heteroaryl, or a five to six-membered heterocycloalkyl;
wherein each R A is independently H or C 1 -C 3 alkyl, and each R B is independently H, C 1 -C 3 alkyl, C 1 -C 3 fluoroalkyl, C 1 -C 3 hydroxyalkyl, —S(O) 1-2 (C 1 -C 3 alkyl), —C(O)(C 1 -C 3 alkyl) or —CO 2 (C 1 -C 3 alkyl).
2. The compound according to claim 1 , wherein the moiety
is
3. The compound according to claim 1 , wherein R 1 is hydrogen, halo, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, —CO 2 H, —(C 0 -C 4 alkyl)-C(O)O(C 1 -C 6 alkyl), —OR 1a , —(C 1 -C 4 alkyl)OR 1a , —SR 1a , —(C 1 -C 4 alkyl)SR 1a , —NR 1b R 1c , —(C 1 -C 4 alkyl)NR 1b R 1c , —(C 1 -C 4 alkyl)C(O)NR 1b R 1c ,—(C 0 -C 4 alkyl)-aryl, —(C 0 -C 4 alkyl)-heteroaryl, —(C 0 -C 4 alkyl)-cycloalkyl, —(C 0 -C 4 alkyl)-heterocycloalkyl, or oxo.
4. The compound according to claim 1 , wherein R 2 is hydrogen, halo, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, —CO 2 H, —(C 0 -C 4 alkyl)-C(O)O(C 1 -C 6 alkyl), —OR 2a , —(C 1 -C 4 alkyl)OR 2a , —SR 2a , —(C 1 -C 4 alkyl)SR 2a , —NR 2b R 2c , —(C 1 -C 4 alkyl)NR 2b R 2c , —(C 1 -C 4 alkyl)C(O)NR 2b R 2c ,—(C 0 -C 4 alkyl)-aryl, —(C 0 -C 4 alkyl)-heteroaryl, —(C 0 -C 4 alkyl)-cycloalkyl, —(C 0 -C 4 alkyl)-heterocycloalkyl, or oxo.
5. The compound according to claim 1 , wherein R 5 is hydrogen, C 1 -C 6 alkyl, —(C 1 -C 4 alkyl)-O—(C 0 -C 4 alkyl), —C(O)(C 1 -C 4 alkyl), —C(O)O(C 1 -C 4 alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 4 alkyl), or —C(O)N(C 1 -C 4 alkyl) 2 .
6. The compound according to claim 1 , wherein R 6 is hydrogen or —OR 6a , wherein R 6a is hydrogen, C 1 -C 6 alkyl, —(C 1 -C 4 alkyl)-O—(C 0 -C 4 alkyl), —C(O)(C 1 -C 4 alkyl), —C(O)O(C 1 -C 4 alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 4 alkyl), or —C(O)N(C 1 -C 4 alkyl) 2 .
7. The compound according to claim 1 , wherein the compound is of formula:
8. The compound according to claim 1 , wherein each R 7 is independently oxo, C 1 -C 4 alkyl, —Cl, —F, —Br, —CN, —SF 5 , —N 3 , nitro, —SR A , —S(O) 1-2 R A , —OR A , —NR B R A , —C(O)R A , —C(O)NR B R A , —NR B C(O)R A , —C(S)NR B R A , —NR B C(S)R A , —CO 2 R A , —OC(O)R A , —C(O)SR A , —SC(O)R A , —C(S)OR A , —OC(S)R A , —C(S)SR A , —SC(S)R A , —S(O) 1-2 OR A , —OS(O) 1-2 R A , —S(O) 1-2 NR B R A , or —NR B S(O) 1-2 R A .
9. The compound according to claim 1 , wherein each R 8 is independently C 1 -C 4 alkyl, —Cl, —F, —Br, —CN, —SF 5 , —N 3 , nitro, —SR A , —S(O) 1-2 R A , —OR A , —NR B R A , —C(O)R A , —C(O)NR B R A , —NR B C(O)R A , —C(S)NR B R A , —NR B C(S)R A , —C 2 R A , —OC(O)R A , —C(O)SR A ,—SC(O)R A , —C(S)OR A , —OC(S)R A , —C(S)SR A , —SC(S)R A , —S(O) 1-2 OR A , —OS(O) 1-2 R A , —S(O) 1-2 NR B R A , or —NR B S(O) 1-2 R A .
10. The compound according to claim 1 , which is:
2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-sulfonic acid;
sodium 2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-sulfonate;
3′-methyl-3-(methylsulfonyl)-4-pentyl-[1,1′-biphenyl]-2,6-diol;
3-(cyclopropylsulfonyl)-3′-methyl-4-pentyl-[1,1′-biphenyl]-2,6-diol;
3-(tert-butylsulfonyl)-3′-methyl-4-pentyl-[1,1′-biphenyl]-2,6-diol;
3-(benzylsulfonyl)-3′-methyl-4-pentyl-[1,1′-biphenyl]-2,6-diol;
3′-methyl-4-pentyl-3-(phenylsulfonyl)-[1,1′-biphenyl]-2,6-diol;
3′-methyl-3-((4-nitrophenyl)sulfonyl)-4-pentyl-[1,1′-biphenyl]-2,6-diol;
3′-methyl-4-pentyl-3-(pyridin-3-ylsulfonyl)-[1,1′-biphenyl]-2,6-diol;
3-(furan-3-ylsulfonyl)-3′-methyl-4-pentyl-[1,1′-biphenyl]-2,6-diol;
3-((1H-imidazol-4-yl)sulfonyl)-3′-methyl-4-pentyl-[1,1′-biphenyl]-2,6-diol;
3′-methyl-3-(oxetan-3-ylsulfonyl)-4-pentyl-[1,1′-biphenyl]-2,6-diol;
3′-methyl-4-pentyl-3-((perfluorophenyl)sulfonyl)-[1,1′-biphenyl]-2,6-diol;
4-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)cyclohexan-1-one;
1-(2-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)ethyl)pyrrolidine-2,5-dione;
3-((2-(dimethylamino)ethyl)sulfonyl)-3′-methyl-4-pentyl-[1,1′-biphenyl]-2,6-diol;
1-(3-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)piperidin-1-yl)ethan-1-one;
3-((2-chloropyrimidin-5-yl)sulfonyl)-3′-methyl-4-pentyl-[1,1′-biphenyl]-2,6-diol;
2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-N,3′-dimethyl-4-pentyl-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-N,N,3′-trimethyl-4-pentyl-[1,1′-biphenyl]-3-sulfonamide;
N-cyclopropyl-2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-N-isopropyl-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-3′-methyl-4-pentyl-N-phenyl-[1,1′-biphenyl]-3-sulfonamide;
N-benzyl-2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-sulfonamide;
3′-methyl-3-((4-methylpiperazin-1-yl)sulfonyl)-4-pentyl-[1,1′-biphenyl]-2,6-diol;
3′-methyl-4-pentyl-3-(piperidin-1-ylsulfonyl)-[1,1′-biphenyl]-2,6-diol;
3′-methyl-3-(morpholinosulfonyl)-4-pentyl-[1,1′-biphenyl]-2,6-diol;
2,6-dihydroxy-3′-methyl-4-pentyl-N-(pyridin-3-yl)-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-3′-methyl-4-pentyl-N-(pyrimidin-2-yl)-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-3′-methyl-N-(2-oxopropyl)-4-pentyl-[1,1′-biphenyl]-3-sulfonamide;
1-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)azetidin-3-one;
2,6-dihydroxy-3′-methyl-N-(oxetan-2-ylmethyl)-4-pentyl-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-3′-methyl-N-(oxetan-2-ylmethyl)-4-pentyl-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-3′-methyl-N-(oxetan-2-ylmethyl)-4-pentyl-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-3′-methyl-N-(oxetan-2-ylmethyl)-4-pentyl-[1,1′-biphenyl]-3-sulfonamide;
methyl ((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)alaninate;
N-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)-3-morpholinopropanamide;
4-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl])-3-sulfonamido)-4-oxobutanoic acid;
4-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl])-3-sulfonamido)-4-oxobutanoic acid;
2-amino-N-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)acetamide;
N-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)-2-(2-methoxyethoxy)acetamide;
2-amino-N-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)-3-hydroxypropanamide;
2-amino-N-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)propanamide;
3-amino-N-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)-2-methylpropanamide;
N-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)acetamide;
N-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)-3-oxobutanamide;
N-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)-2-(3-methyl-1H-1,2,4-triazol-5-yl)acetamide;
N-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)-1H-1,2,4-triazole-5-carboxamide;
N-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)oxetane-2-carboxamide;
N-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)benzamide;
N-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)nicotinamide;
N-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)-2-phenylacetamide;
N-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)-2-(furan-2-yl)acetamide;
N-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)-2-(oxazol-2-yl)acetamide;
N-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)-2-(thiazol-2-yl)acetamide;
2-(1H-benzo[d]imidazol-2-yl)-N-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)acetamide;
2,6-dihydroxy-3′-methyl-4-pentyl-N-(phenylsulfonyl)-[1,1′-biphenyl]-3-carboxamide;
N-(cyclohexylsulfonyl)-2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-carboxamide;
(E)-2,6-dihydroxy-3′-methyl-4-pentyl-N-(prop-1-en-1-ylsulfonyl)-[1,1′-biphenyl]-3-carboxamide;
N-((1H-benzo[d]imidazol-2-yl)sulfonyl)-2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-carboxamide;
N,N-diethyl-2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-sulfonamide;
N-(2-bromoethyl)-2,6-dihydroxy-N-(2-hydroxyethyl)-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-sulfonamide;
2,2,2-trifluoroethyl 2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-sulfonate;
-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)-4-(trifluoromethyl)benzamide;
N-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)pivalamide;
2,6-dihydroxy-N,N,3′-trimethyl-4-propyl-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-N-isopropyl-3′-methyl-4-propyl-[1,1′-biphenyl]-3-sulfonamide;
3-(ethylsulfonyl)-3′-methyl-4-pentyl-[1,1′-biphenyl]-2,6-diol;
tert-butyl 4-((2,6-dihydroxy-3′-methyl-4-pentyl-[1,1′-biphenyl]-3-yl)sulfonyl)piperazine-1-carboxylate;
2,6-dihydroxy-3′-methyl-4-pentyl-N-(pyridin-3-ylsulfonyl)-[1,1′-biphenyl]-3-carboxamide;
2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-sulfonic acid;
sodium 2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-sulfonate;
5′-methyl-3-(methylsulfonyl)-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-2,6-diol;
3-(cyclopropylsulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-2,6-diol;
3-(tert-butylsulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-2,6-diol;
3-(benzylsulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-2,6-diol;
5′-methyl-4-pentyl-3-(phenylsulfonyl)-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-2,6-diol;
5′-methyl-3-((4-nitrophenyl)sulfonyl)-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-2,6-diol;
5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-3-(pyridin-3-ylsulfonyl)-[1,1′-biphenyl]-2,6-diol;
3-(furan-3-ylsulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-2,6-diol;
3-((1H-imidazol-4-yl)sulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-2,6-diol;
5′-methyl-3-(oxetan-3-ylsulfonyl)-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-2,6-diol;
5′-methyl-4-pentyl-3-((perfluorophenyl)sulfonyl)-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-2,6-diol;
4-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)cyclohexan-1-one;
1-(2-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)ethyl)pyrrolidine-2,5-dione;
3-((2-(dimethylamino)ethyl)sulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-2,6-diol;
1-(3-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)piperidin-1-yl)ethan-1-one;
3-((2-chloropyrimidin-5-yl)sulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-2,6-diol;
2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-N,5′-dimethyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-N,N,5′-trimethyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-sulfonamide;
N-cyclopropyl-2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-N-isopropyl-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-5′-methyl-4-pentyl-N-phenyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-sulfonamide;
N-benzyl-2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-sulfonamide;
5′-methyl-3-((4-methylpiperazin-1-yl)sulfonyl)-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-2,6-diol;
5′-methyl-4-pentyl-3-(piperidin-1-ylsulfonyl)-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-2,6-diol;
5′-methyl-3-(morpholinosulfonyl)-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-2,6-diol;
2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-N-(pyridin-3-yl)-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-N-(pyrimidin-2-yl)-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-N-(pyrimidin-2-yl)-[1,1′-biphenyl]-3-sulfonamide;
1-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)azetidin-3-one;
2,6-dihydroxy-5′-methyl-N-(oxetan-2-ylmethyl)-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-sulfonamide;
3-((2-azaspiro[3.3]heptan-2-yl)sulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-2,6-diol;
3-((2,6-diazaspiro[3.3]heptan-2-yl)sulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-2,6-diol;
((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)alanine;
methyl ((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)alaninate;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)-3-morpholinopropanamide;
4-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl])-3-sulfonamido)-4-oxobutanoic acid;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)-3-(4-methylpiperazin-1-yl)propanamide;
2-amino-N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)acetamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)-2-(2-methoxyethoxy)acetamide;
2-amino-N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)-3-hydroxypropanamide;
2-amino-N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)propanamide;
3-amino-N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)-2-methylpropanamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)acetamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)-3-oxobutanamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)-3-oxobutanamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)-3-oxobutanamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)-3-oxobutanamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)-3-oxobutanamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)nicotinamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)-2-phenylacetamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)-2-(furan-2-yl)acetamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)-2-(oxazol-2-yl)acetamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)-2-(thiazol-2-yl)acetamide;
2-(1H-benzo[d]imidazol-2-yl)-N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)acetamide;
2,6-dihydroxy-5′-methyl-4-pentyl-N-(phenylsulfonyl)-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-carboxamide;
N-(cyclohexylsulfonyl)-2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-carboxamide;
(E)-2,6-dihydroxy-5′-methyl-4-pentyl-N-(prop-1-en-1-ylsulfonyl)-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-carboxamide;
N-((1H-benzo[d]imidazol-2-yl)sulfonyl)-2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-carboxamide;
N,N-diethyl-2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-sulfonamide;
N-(2-bromoethyl)-2,6-dihydroxy-N-(2-hydroxyethyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-sulfonamide;
2,2,2-trifluoroethyl 2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-sulfonate;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)-4-(trifluoromethyl)benzamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)pivalamide;
2,6-dihydroxy-N,N,5′-trimethyl-2′-(prop-1-en-2-yl)-4-propyl-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-N,N,5′-trimethyl-2′-(prop-1-en-2-yl)-4-propyl-[1,1′-biphenyl]-3-sulfonamide;
3-(ethylsulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-2,6-diol;
tert-butyl 4-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-[1,1′-biphenyl]-3-yl)sulfonyl)piperazine-1-carboxylate;
2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-N-(pyridin-3-ylsulfonyl)-[1,1′-biphenyl]-3-carboxamide;
2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonic acid;
sodium 2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonate;
5′-methyl-3-(methylsulfonyl)-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
3-(cyclopropylsulfonyl)-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
3-(tert-butylsulfonyl)-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
3-(benzylsulfonyl)-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
5′-methyl-4-pentyl-3-(phenylsulfonyl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
5′-methyl-3-((4-nitrophenyl)sulfonyl)-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
5′-methyl-4-pentyl-3-(pyridin-3-ylsulfonyl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
3-(furan-3-ylsulfonyl)-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
3-((1H-imidazol-4-yl)sulfonyl)-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
5′-methyl-3-(oxetan-3-ylsulfonyl)-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
5′-methyl-4-pentyl-3-((perfluorophenyl)sulfonyl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
4-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)cyclohexan-1-one;
1-(2-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)ethyl)pyrrolidine-2,5-dione;
3-((2-(dimethylamino)ethyl)sulfonyl)-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
1-(3-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)piperidin-1-yl)ethan-1-one;
3-((2-chloropyrimidin-5-yl)sulfonyl)-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-N,N,5′-trimethyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
N-cyclopropyl-2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-N-isopropyl-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-5′-methyl-4-pentyl-N-phenyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
N-benzyl-2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
5′-methyl-3-((4-methylpiperazin-1-yl)sulfonyl)-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
5′-methyl-4-pentyl-3-(piperidin-1-ylsulfonyl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
5′-methyl-3-(morpholinosulfonyl)-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
2,6-dihydroxy-5′-methyl-4-pentyl-N-(pyridin-3-yl)-1′, 2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-5′-methyl-4-pentyl-N-(pyrimidin-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-5′-methyl-N-(2-oxopropyl)-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
1-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)azetidin-3-one;
2,6-dihydroxy-5′-methyl-N-(oxetan-2-ylmethyl)-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
3-((2-azaspiro[3.3]heptan-2-yl)sulfonyl)-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
3-((2,6-diazaspiro[3.3]heptan-2-yl)sulfonyl)-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
3-((2,6-diazaspiro[3.3]heptan-2-yl)sulfonyl)-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
methyl ((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)alaninate;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-3-morpholinopropanamide;
4-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl])-3-sulfonamido)-4-oxobutanoic acid;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-3-(4-methylpiperazin-1-yl)propanamide;
2-amino-N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)acetamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-2-(2-methoxyethoxy)acetamide;
2-amino-N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-3-hydroxypropanamide;
2-amino-N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)propanamide;
3-amino-N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-2-methylpropanamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)acetamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-3-oxobutanamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-2-(3-methyl-1H-1,2,4-triazol-5-yl)acetamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-1H-1,2,4-triazole-5-carboxamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)oxetane-2-carboxamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)benzamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)nicotinamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-2-phenylacetamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-2-(furan-2-yl)acetamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-2-(oxazol-2-yl)acetamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-2-(thiazol-2-yl)acetamide;
2-(1H-benzo[d]imidazol-2-yl)-N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)acetamide;
2,6-dihydroxy-5′-methyl-4-pentyl-N-(phenylsulfonyl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-carboxamide;
N-(cyclohexylsulfonyl)-2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-carboxamide;
(E)-2,6-dihydroxy-5′-methyl-4-pentyl-N-(prop-1-en-1-ylsulfonyl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-carboxamide;
N-((1H-benzo[d]imidazol-2-yl)sulfonyl)-2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-carboxamide;
N,N-diethyl-2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
N-(2-bromoethyl)-2,6-dihydroxy-N-(2-hydroxyethyl)-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
2,2,2-trifluoroethyl 2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonate;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-4-(trifluoromethyl)benzamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)pivalamide;
2,6-dihydroxy-N,N,5′-trimethyl-4-propyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-N-isopropyl-5′-methyl-4-propyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
3-(ethylsulfonyl)-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
tert-butyl 4-((2,6-dihydroxy-5′-methyl-4-pentyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)piperazine-1-carboxylate;
2,6-dihydroxy-5′-methyl-4-pentyl-N-(pyridin-3-ylsulfonyl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-carboxamide;
2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonic acid;
sodium 2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonate;
5′-methyl-3-(methylsulfonyl)-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
3-(cyclopropylsulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
3-(tert-butylsulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
3-(benzylsulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
5′-methyl-4-pentyl-3-(phenylsulfonyl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
5′-methyl-4-pentyl-3-(phenylsulfonyl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-3-(pyridin-3-ylsulfonyl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
3-(furan-3-ylsulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
3-((1H-imidazol-4-yl)sulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
5′-methyl-3-(oxetan-3-ylsulfonyl)-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
5′-methyl-3-(oxetan-3-ylsulfonyl)-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
4-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)cyclohexan-1-one;
1-(2-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)ethyl)pyrrolidine-2,5-dione;
3-((2-(dimethylamino)ethyl)sulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
1-(3-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)piperidin-1-yl)ethan-1-one;
3-((2-chloropyrimidin-5-yl)sulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-N,5′-dimethyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-N,N,5′-trimethyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
N-cyclopropyl-2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-N-isopropyl-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-5′-methyl-4-pentyl-N-phenyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
N-benzyl-2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
5′-methyl-3-((4-methylpiperazin-1-yl)sulfonyl)-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
5′-methyl-4-pentyl-3-(piperidin-1-ylsulfonyl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
5′-methyl-3-(morpholinosulfonyl)-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-N-(pyrimidin-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-5′-methyl-N-(2-oxopropyl)-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
1-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)azetidin-3-one;
2,6-dihydroxy-5′-methyl-N-(oxetan-2-ylmethyl)-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
3-((2-azaspiro[3.3]heptan-2-yl)sulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
3-((2,6-diazaspiro[3.3]heptan-2-yl)sulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)alanine;
methyl ((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)alaninate;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-3-morpholinopropanamide;
4-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl])-3-sulfonamido)-4-oxobutanoic acid;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-3-(4-methylpiperazin-1-yl)propanamide;
2-amino-N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)acetamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-2-(2-methoxyethoxy)acetamide;
2-amino-N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-3-hydroxypropanamide;
2-amino-N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)propanamide;
3-amino-N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-2-methylpropanamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)acetamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-3-oxobutanamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-2-(3-methyl-1H-1,2,4-triazol-5-yl)acetamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-1H-1,2,4-triazole-5-carboxamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)oxetane-2-carboxamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)oxetane-2-carboxamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)nicotinamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-2-phenylacetamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-2-(furan-2-yl)acetamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-2-(oxazol-2-yl)acetamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-2-(thiazol-2-yl)acetamide;
2-(1H-benzo[d]imidazol-2-yl)-N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)acetamide;
2-(1H-benzo[d]imidazol-2-yl)-N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)acetamide;
2-(1H-benzo[d]imidazol-2-yl)-N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)acetamide;
(E)-2,6-dihydroxy-5′-methyl-4-pentyl-N-(prop-1-en-1-ylsulfonyl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-carboxamide;
(E)-2,6-dihydroxy-5′-methyl-4-pentyl-N-(prop-1-en-1-ylsulfonyl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-carboxamide;
N,N-diethyl-2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
N-(2-bromoethyl)-2,6-dihydroxy-N-(2-hydroxyethyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′, 2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
2,2,2-trifluoroethyl-2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonate;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)-4-(trifluoromethyl)benzamide;
N-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)pivalamide;
2,6-dihydroxy-N,N,5′-trimethyl-2′-(prop-1-en-2-yl)-4-propyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
2,6-dihydroxy-N-isopropyl-5′-methyl-2′-(prop-1-en-2-yl)-4-propyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-sulfonamide;
3-(ethylsulfonyl)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol;
tert-butyl 4-((2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-yl)sulfonyl)piperazine-1-carboxylate; or
2,6-dihydroxy-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-N-(pyridin-3-ylsulfonyl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-3-carboxamide.
11. A pharmaceutical composition comprising a compound of claim 1 , or an enantiomer, diastereomer, racemate, or tautomer thereof, or a pharmaceutically acceptable salt, solvate or hydrate of the compound, enantiomer, diastereomer, racemate, or tautomer, together with a pharmaceutically acceptable excipient, diluent, or carrier.
12. A method of treating a disease associated with a cannabinoid receptor in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound according to claim 1 .
13. The method according to claim 12 , wherein the cannabinoid receptor is one or more of CB1, CB2, 5HT1A, 5HT2A, GPR18, GPR55, GPR119, TRPV1, TPRV2, PPARγ or a μ-opioid receptor.
14. The method according to claim 13 , wherein the cannabinoid receptor is CB1 or CB2.
15. A method of treating a disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound according to claim 1 , wherein the disease is acute pain, ADHD/ADD, alcohol use disorder, allergic asthma, ALS, Alzheimer's, anorexia, anxiety disorders, social anxiety disorder, specific phobia, test anxiety, generalized anxiety disorder, arthritis, atherosclerosis, autism, bipolar disorder, burns, cancer, cancer pain, Charcot-Marie-Tooth disease, chronic inflammatory demyelinating polyneuropathies, chronic pain, chronic allograft nephropathy, cocaine use disorder, complex regional pain syndrome, congestive heart failure, depression, fibromyalgia, fragile X syndrome/FXTAS, frontotemporal dementias, gingivitis pyrexia, glaucoma, glioblastoma, glomerulonephropathy, Huntington's disease, hypertrophic scars, IBD/IBS, inflammation, Inflammatory myopathies, ischemia, kidney fibrosis, keloids, leukodystrophies, liver fibrosis, liver cirrhosis, lung fibrosis, migraine, multiple sclerosis, myocardial infarction, nausea, neuropathic pain, postherpetic neuralgia, painful diabetic neuropathy, nightmare disorder, non-alcoholic fatty liver disease, obesity, obsessive-compulsive disorder, opioid sparing, opioid use disorder, osteoarthritis, osteoporosis, Parkinson's, post-concussion syndrome/traumatic brain injury, psychosis/schizophrenia, PTSD, regulation of bone mass, REM sleep behaviour disorder, reperfusion injury, Rett syndrome, rheumatoid arthritis, skin conditions, acne, psoriatic arthritis, sleep disorders, spinocerebellar ataxias, systemic fibrosis, systemic sclerosis, thermal injury, tobacco use disorder/nicotine dependence, Tourette's, tumors, or trigeminal neuralgia.
16. A method of treating a disease associated with a cannabinoid receptor in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition according to claim 11 .
17. The method according to claim 16 , wherein the cannabinoid receptor is one or more of CB1, CB2, 5HT1A, 5HT2A, GPR18, GPR55, GPR119, TRPV1, TPRV2, PPARγ or a μ-opioid receptor.
18. The method according to claim 1 , wherein the cannabinoid receptor is CB1 or CB2.
19. A method of treating a disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition according to claim 11 , wherein the disease is acute pain, ADHD/ADD, alcohol use disorder, allergic asthma, ALS, Alzheimer's, anorexia, anxiety disorders, social anxiety disorder, specific phobia, test anxiety, generalized anxiety disorder, arthritis, atherosclerosis, autism, bipolar disorder, burns, cancer, cancer pain, Charcot-Marie-Tooth disease, chronic inflammatory demyelinating polyneuropathies, chronic pain, chronic allograft nephropathy, cocaine use disorder, complex regional pain syndrome, congestive heart failure, depression, fibromyalgia, fragile X syndrome/FXTAS, frontotemporal dementias, gingivitis pyrexia, glaucoma, glioblastoma, glomerulonephropathy, Huntington's disease, hypertrophic scars, IBD/IBS, inflammation, Inflammatory myopathies, ischemia, kidney fibrosis, keloids, leukodystrophies, liver fibrosis, liver cirrhosis, lung fibrosis, migraine, multiple sclerosis, myocardial infarction, nausea, neuropathic pain, postherpetic neuralgia, painful diabetic neuropathy, nightmare disorder, non-alcoholic fatty liver disease, obesity, obsessive-compulsive disorder, opioid sparing, opioid use disorder, osteoarthritis, osteoporosis, Parkinson's, post-concussion syndrome/traumatic brain injury, psychosis/schizophrenia, PTSD, regulation of bone mass, REM sleep behaviour disorder, reperfusion injury, Rett syndrome, rheumatoid arthritis, skin conditions, acne, psoriatic arthritis, sleep disorders, spinocerebellar ataxias, systemic fibrosis, systemic sclerosis, thermal injury, tobacco use disorder/nicotine dependence, Tourette's, tumors, or trigeminal neuralgia.