Indene derivatives useful in treating pain and inflammation

1. A compound of formula (I):

wherein:

is an optionally substituted fused 5- or 6-membered N-heteroaryl;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a is —R 9 —OR 7 and R 4b is hydrogen, alkyl or optionally substituted heteroaryl;

or R 4a is an optionally substituted aryl and R 4 is a bond to C16;

or R 4a and R 4b together form alkylidene, provided that

is a fused 5- or 6-membered N-heteroaryl substituted by substituted aryl, substituted aralkyl, substituted cycloalkyl or substituted heteroaryl;

or R 4a is alkyl and R 4b is hydrogen, provided that

is a fused 5- or 6-membered N-heteroaryl substituted by substituted aryl, substituted aralkyl, substituted cycloalkyl or substituted heteroaryl;

or R 4a and R 1 together form an optionally substituted bicyclic heterocyclyl and R 4b is hydrogen;

or R 4a , R 4b and R 1 together form a fused optionally substituted heteroaryl;

R 5 is alkyl or R 5 is a direct bond to the carbon at C14;

each R 6 is independently selected from a direct bond or a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl;

each R 8 is independently selected from hydrogen or alkyl; and

R 9 is a direct bond or a straight or branched alkylene chain;

or a stereoisomer, enantiomer or tautomer thereof or mixtures thereof, or a pharmaceutically acceptable salt or solvate thereof.

2. The compound of claim 1 wherein:

is an optionally substituted fused 5- or 6-membered N-heteroaryl;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a is —R 9 —OR 7 and R 4b is hydrogen, alkyl or optionally substituted heteroaryl;

R 5 is alkyl or R 5 is a direct bond to the carbon at C14;

each R 6 is independently selected from a direct bond or a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl;

each R 8 is independently selected from hydrogen or alkyl; and

R 9 is a direct bond or a straight or branched alkylene chain.

3. The compound of claim 2 wherein:

is an optionally substituted fused 5- or 6-membered N-heteroaryl;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a is —R 9 —OR 7 and R 4b is hydrogen, alkyl or optionally substituted heteroaryl;

R 5 is alkyl;

each R 6 is a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl;

each R 8 is independently selected from hydrogen or alkyl; and

R 9 is a direct bond.

4. The compound of claim 3 wherein:

is a fused 5-membered N-heteroaryl optionally substituted by one or more substitutents selected from alkyl, haloalkyl, —C(O)OR 7 , —N(R 8 ) 2 , —C(O)N(R 8 ) 2 or optionally substituted aryl;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a is —R 9 —OR 7 and R 4b is hydrogen, alkyl or optionally substituted heteroaryl;

R 5 is alkyl;

each R 6 is a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl;

each R 8 is independently selected from hydrogen or alkyl; and

R 9 is a direct bond.

5. The compound of claim 4 selected from:

(1S,3aS,4R,5S,7aS)-4-(hydroxymethyl)-5-((5R,6S)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)-7a-methyloctahydro-1H-inden-1-ol;

(1R,3aS,4R,5S,7aS)-4-(hydroxymethyl)-5-((5R,6S)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)-7a-methyloctahydro-1H-inden-1-ol;

(1S,3aS,4R,5S,7aS)-4-(hydroxymethyl)-5-((5R,6S)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)-1,7a-dimethyloctahydro-1H-inden-1-ol;

(1S,3aS,4R,5S,7aS)-4-(hydroxymethyl)-5-((5R,6S)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)-7a-methyl-1-(pyridin-2-yl)octahydro-1H-inden-1-ol;

(1S,3aS,4R,5S,7aS)-4-(hydroxymethyl)-5-((5R,6S)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)-7a-methyl-1-(thiazol-2-yl)octahydro-1H-inden-1-ol;

(1S,3aS,4R,5S,7aS)-4-(aminomethyl)-5-((5R,6S)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)-7a-methyl-1-(thiazol-2-yl)octahydro-1H-inden-1-ol; and

(1S,3aS,4R,5S,7aS)-4-(aminomethyl)-5-((5R,6S)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)-7a-methyl-1-(pyridin-2-yl)octahydro-1H-inden-1-ol.

6. The compound of claim 2 wherein:

is an optionally substituted fused 5- or 6-membered N-heteroaryl;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a is —R 9 —OR 7 and R 4b is hydrogen, alkyl or optionally substituted heteroaryl;

R 5 is alkyl;

each R 6 is a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl;

each R 8 is independently selected from hydrogen or alkyl; and

R 9 is straight or branched alkylene chain.

7. The compound of claim 6 wherein:

is a fused 5-membered N-heteroaryl optionally substituted by one or more substitutents selected from alkyl, haloalkyl, —C(O)OR 7 , —N(R 8 ) 2 , —C(O)N(R 8 ) 2 or optionally substituted aryl;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a is —R 9 —OR 7 and R 4b is hydrogen, alkyl or optionally substituted heteroaryl;

R 5 is alkyl;

each R 6 is a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl;

each R 8 is independently selected from hydrogen or alkyl; and

R 9 is a straight or branched alkylene chain.

8. The compound of claim 7 selected from:

(2S,5R)-5-ethyl-2-((1R,3aS,4S,5S,7aS)-4-(hydroxymethyl)-5-((5R,6S)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)-7a-methyloctahydro-1H-inden-1-yl)-6-methylheptan-3-ol.

9. The compound of claim 1 wherein:

is an optionally substituted fused 5- or 6-membered N-heteroaryl;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a and R 1 together form an optionally substituted bicyclic heterocyclyl and R 4b is hydrogen;

R 5 is alkyl or R 5 is a direct bond to the carbon at C14;

each R 6 is independently selected from a direct bond or a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl; and

each R 8 is independently selected from hydrogen or alkyl.

10. The compound of claim 9 wherein:

is an optionally substituted fused 5- or 6-membered N-heteroaryl;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a and R 1 together form an optionally substituted bicyclic heterocyclyl and R 4b is hydrogen;

R 5 is alkyl;

each R 6 is a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl; and

each R 8 is independently selected from hydrogen or alkyl.

11. The compound of claim 10 wherein:

is a fused 5-membered N-heteroaryl optionally substituted by one or more substitutents selected from alkyl, haloalkyl, —C(O)OR 7 , —N(R 8 ) 2 , —C(O)N(R 8 ) 2 or optionally substituted aryl;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a and R 1 together form an optionally substituted bicyclic heterocyclyl and R 4b is hydrogen;

R 5 is alkyl;

each R 6 is a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl; and

each R 8 is independently selected from hydrogen or alkyl.

12. The compound of claim 11 selected from:

((5R,6S)-5-((2R,3S,3aR,3bS,5′R,6S,7R,7aS,8aS)-7-(hydroxymethyl)-3,3b,5′-trimethyltetradecahydrospiro[indeno[2,1-b]furan-2,2′-pyran]-6-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol; and

((5R,6S)-5-((2R,3S,3aR,3bS,5′R,6S,7R,7aS,8aS)-7-(aminomethyl)-3,3b,5′-trimethyltetradecahydrospiro[indeno[2,1-b]furan-2,2′-pyran]-6-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol.

13. The compound of claim 1 wherein:

is an optionally substituted fused 5- or 6-membered N-heteroaryl;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

or R 4a , R 4b and R 1 together form a fused optionally substituted heteroaryl;

R 5 is alkyl or R 5 is a direct bond to the carbon at C14;

each R 6 is independently selected from a direct bond or a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl; and

each R 8 is independently selected from hydrogen or alkyl.

14. The compound of claim 13 wherein:

is an optionally substituted fused 5- or 6-membered N-heteroaryl;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

or R 4a , R 4b and R 1 together form a fused optionally substituted heteroaryl;

R 5 is alkyl;

each R 6 is a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl; and

each R 8 is independently selected from hydrogen or alkyl.

15. The compound of claim 14 wherein:

is a fused 5-membered N-heteroaryl optionally substituted by one or more substitutents selected from alkyl, haloalkyl, —C(O)OR 7 , —N(R 8 ) 2 , —C(O)N(R 8 ) 2 or optionally substituted aryl;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

or R 4a , R 4b and R 1 together form a fused optionally substituted heteroaryl;

R 5 is alkyl;

each R 6 is a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl; and

each R 8 is independently selected from hydrogen or alkyl.

16. The compound of claim 15 selected from:

((4aS,5R,6S,8aS)-6-((5R,6S)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)-8a-methyl-1,4,4a,5,6,7,8,8a-octahydroindeno[1,2-c]pyrazol-5-yl)methanol;

((5R,6S)-5-((4aS,5R,6S,8aS)-5-(aminomethyl)-8a-methyl-1,4,4a,5,6,7,8,8a-octahydroindeno[1,2-c]pyrazol-6-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;

((5R,6S)-5-((5aS,6R,7S,9aS)-6-(aminomethyl)-9a-methyl-5a,6,7,8,9,9a-hexahydro-5H-indeno[1,2-b]pyridin-7-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol; and

((5aS,6R,7S,9aS)-7-((5R,6S)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)-9a-methyl-5a,6,7,8,9,9a-hexahydro-5H-indeno[1,2-b]pyridin-6-yl)methanol.

17. The compound of claim 1 wherein:

is an optionally substituted fused 5- or 6-membered N-heteroaryl;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a is an optionally substituted aryl and R 4b is a bond to C16;

R 5 is alkyl or R 5 is a direct bond to the carbon at C14;

each R 6 is independently selected from a direct bond or a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl; and

each R 8 is independently selected from hydrogen or alkyl.

18. The compound of claim 17 wherein:

is an optionally substituted fused 5- or 6-membered N-heteroaryl;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a is an optionally substituted aryl and R 4 is a bond to C16;

R 5 is alkyl;

each R 6 is a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl; and

each R 8 is independently selected from hydrogen or alkyl.

19. The compound of claim 18 wherein:

is a fused 5-membered N-heteroaryl optionally substituted by one or more substitutents selected from alkyl, haloalkyl, —C(O)OR 7 , —N(R 8 ) 2 , —C(O)N(R 8 ) 2 or optionally substituted aryl;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a is an optionally substituted aryl and R 4b is a bond to C16;

R 5 is alkyl;

each R 6 is a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl; and

each R 8 is independently selected from hydrogen or alkyl.

20. The compound of claim 19 selected from:

((5R,6S)-5-((3aS,6S,7R,7aS)-7-(aminomethyl)-3a-methyl-3-phenyl-3a,4,5,6,7,7a-hexahydro-1H-inden-6-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol; and

((5R,6S)-5-((3aS,6S,7R,7aS)-7-(hydroxymethyl)-3a-methyl-3-phenyl-3a,4,5,6,7,7a-hexahydro-1H-inden-6-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol.

21. The compound of claim 1 wherein:

is a fused 5- or 6-membered N-heteroaryl substituted by substituted aryl, substituted aralkyl, substituted cycloalkyl or substituted heteroaryl;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a and R 4b together form alkylidene;

R 5 is alkyl or R 5 is a direct bond to the carbon at C14;

each R 6 is independently selected from a direct bond or a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl; and

each R 8 is independently selected from hydrogen or alkyl.

22. The compound of claim 21 wherein:

is a fused pyrazolyl substituted by substituted aryl, substituted aralkyl, substituted cycloalkyl or substituted heteroaryl;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a and R 4b together form alkylidene;

R 5 is alkyl or R 5 is a direct bond to the carbon at C14;

each R 6 is independently selected from a direct bond or a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl; and

each R 8 is independently selected from hydrogen or alkyl.

23. The compound of claim 22 wherein:

is a fused pyrazolyl substituted by aryl substituted by one or more substituents selected from halo, —R 10 —OR 11 , —R 10 —C(O)R 11 or —R 10 —C(O)OR 11 ;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a and R 4b together form alkylidene;

R 5 is alkyl or R 5 is a direct bond to the carbon at C14;

each R 6 is independently selected from a direct bond or a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl;

each R 8 is independently selected from hydrogen or alkyl;

each R 10 is independently a direct bond or a straight or branched alkylene chain; and

each R 11 is independently hydrogen, alkyl, cycloalkyl or optionally substituted aryl.

24. The compound of claim 23 selected from:

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-1-(4-fluorophenyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;

4-(4-((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-1-yl)phenoxy)benzoic acid;

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-2-(4-methoxyphenyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol;

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-2-(4-fluorophenyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol;

(4-((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-1-yl)phenyl)(phenyl)methanone;

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-1-(2-fluorophenyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-1-(2,4-difluorophenyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-1-(3,4-difluorophenyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-1-(3-fluorophenyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-2-(3,4-difluorophenyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol;

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-2-(4-fluorophenyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol;

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-2-(4-(4-fluorophenoxy)phenyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol;

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-5-methyl-1-(4-phenoxyphenyl)-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-1-(4-(4-fluorophenoxy)phenyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-5-methyl-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol;

(4-((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-2-yl)phenyl)(phenyl)methanone;

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-2-(2-fluorophenyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol;

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-2-(2,4-difluorophenyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol;

4-(4-((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-2-yl)phenoxy)benzoic acid;

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-2-(3-fluorophenyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol;

(4-((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-1-yl)phenyl)(4-(pent-4-yn-1-yloxy)phenyl)methanone;

(4-((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-2-yl)phenyl)(4-(pent-4-yn-1-yloxy)phenyl)methanone;

4-((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-1-yl)benzoic acid; and

4-((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-2-yl)benzoic acid.

25. The compound of claim 22 wherein:

is a fused pyrazolyl substituted by aralkyl substituted by one or more substituents selected from halo, —R 10 —OR 11 or —R 10 —C(O)R 11 ;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a and R 4b together form alkylidene;

R 5 is alkyl or R 5 is a direct bond to the carbon at C14;

each R 6 is independently selected from a direct bond or a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl;

each R 8 is independently selected from hydrogen or alkyl;

each R 10 is independently a direct bond or a straight or branched alkylene chain; and

each R 11 is independently hydrogen, alkyl, cycloalkyl or optionally substituted aryl.

26. The compound of claim 25 selected from:

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-2-(4-methoxybenzyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol;

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-2-(4-fluorobenzyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol;

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-1-(4-methoxybenzyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol; and

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-1-(4-fluorobenzyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol.

27. The compound of claim 22 wherein:

is a fused pyrazolyl substituted by cycloalkyl substituted by one or more substituents selected from halo, —R 10 —OR 11 or —R 10 —C(O)R 11 ;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a and R 4b together form alkylidene;

R 5 is alkyl or R 5 is a direct bond to the carbon at C14;

each R 6 is independently selected from a direct bond or a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl;

each R 8 is independently selected from hydrogen or alkyl;

each R 10 is independently a direct bond or a straight or branched alkylene chain; and

each R 11 is independently hydrogen, alkyl, cycloalkyl or optionally substituted aryl.

28. The compound of claim 27 selected from:

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-2-(4,4-difluorocyclohexyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol; and

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-1-(4,4-difluorocyclohexyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol.

29. The compound of claim 22 wherein:

is a fused pyrazolyl substituted by heteroaryl substituted by one or more substituents selected from halo, —R 10 —OR 11 or —R 10 —C(O)R 11 ;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a and R 4b together form alkylidene;

R 5 is alkyl or R 5 is a direct bond to the carbon at C14;

each R 6 is independently selected from a direct bond or a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl;

each R 8 is independently selected from hydrogen or alkyl;

each R 10 is independently a direct bond or a straight or branched alkylene chain; and

each R 11 is independently hydrogen, alkyl, cycloalkyl or optionally substituted aryl.

30. The compound of claim 29 selected from:

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-1-(5-fluoropyridin-2-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-1-(5-fluoropyrimidin-2-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-2-(5-fluoropyrimidin-2-yl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol; and

((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-2-(5-fluoropyridin-2-yl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol.

31. The compound of claim 1 wherein:

is a fused 5- or 6-membered N-heteroaryl substituted by substituted aryl, substituted aralkyl, substituted cycloalkyl or substituted heteroaryl;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a is alkyl and R 4b is hydrogen;

R 5 is alkyl or R 5 is a direct bond to the carbon at C14;

each R 6 is independently selected from a direct bond or a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl; and

each R 8 is independently selected from hydrogen or alkyl.

32. The compound of claim 31 wherein:

is a fused pyrazolyl substituted by substituted aryl, substituted aralkyl, substituted cycloalkyl or substituted heteroaryl;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a is alkyl and R 4b is hydrogen;

R 5 is alkyl or R 5 is a direct bond to the carbon at C14;

each R 6 is independently selected from a direct bond or a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl; and

each R 8 is independently selected from hydrogen or alkyl.

33. The compound of claim 32 wherein:

is a fused pyrazolyl substituted by aryl substituted by one or more substituents selected from halo, —R 10 —OR 11 or —R 10 —C(O)R 11 ;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a is alkyl and R 4b is hydrogen;

R 5 is alkyl or R 5 is a direct bond to the carbon at C14;

each R 6 is independently selected from a direct bond or a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl;

each R 8 is independently selected from hydrogen or alkyl;

each R 10 independently is a direct bond or a straight or branched alkylene chain; and

each R 11 is independently hydrogen, alkyl, cycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl.

34. The compound of claim 33 selected from:

(4-((5R,6S)-5-((1S,3aS,4S,5S,7aR)-4-(aminomethyl)-1,7a-dimethyloctahydro-1H-inden-5-yl)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-1-yl)phenyl)(phenyl)methanone;

(4-((5R,6S)-5-((1S,3aS,4S,5S,7aR)-4-(aminomethyl)-1,7a-dimethyloctahydro-1H-inden-5-yl)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-2-yl)phenyl)(phenyl)methanone;

((5R,6S)-5-((1S,3aS,4S,5S,7aR)-4-(aminomethyl)-1,7a-dimethyloctahydro-1H-inden-5-yl)-1-(4-fluorophenyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;

((5R,6S)-5-((1S,3aS,4S,5S,7aR)-4-(aminomethyl)-1,7a-dimethyloctahydro-1H-inden-5-yl)-1-(4-methoxyphenyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;

((5R,6S)-5-((1S,3aS,4S,5S,7aR)-4-(aminomethyl)-1,7a-dimethyloctahydro-1H-inden-5-yl)-2-(4-fluorophenyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol;

((5R,6S)-5-((1S,3aS,4S,5S,7aR)-4-(aminomethyl)-1,7a-dimethyloctahydro-1H-inden-5-yl)-2-(4-methoxyphenyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol;

((5R,6S)-5-((1S,3aS,4S,5S,7aR)-4-(aminomethyl)-1,7a-dimethyloctahydro-1H-inden-5-yl)-2-(4-(4-fluorophenoxy)phenyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol;

((5R,6S)-5-((1S,3aS,4S,5S,7aR)-4-(aminomethyl)-1,7a-dimethyloctahydro-1H-inden-5-yl)-1-(4-(4-fluorophenoxy)phenyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;

((5R,6S)-5-((1S,3aS,4S,5S,7aR)-4-(aminomethyl)-1,7a-dimethyloctahydro-1H-inden-5-yl)-1-(4-(4-fluorophenoxy)phenyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol hydrochloride;

((5R,6S)-5-((1S,3aS,4S,5S,7aR)-4-(aminomethyl)-1,7a-dimethyloctahydro-1H-inden-5-yl)-5-methyl-2-(4-(pyridin-2-yloxy)phenyl)-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol;

((5R,6S)-5-((1S,3aS,4S,5S,7aR)-4-(aminomethyl)-1,7a-dimethyloctahydro-1H-inden-5-yl)-5-methyl-1-(4-(pyridin-2-yloxy)phenyl)-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;

((5R,6S)-5-((1S,3aS,4S,5S,7aR)-4-(aminomethyl)-1,7a-dimethyloctahydro-1H-inden-5-yl)-5-methyl-2-(4-(pyridin-4-yloxy)phenyl)-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol;

((5R,6S)-5-((1S,3aS,4S,5S,7aR)-4-(aminomethyl)-1,7a-dimethyloctahydro-1H-inden-5-yl)-5-methyl-1-(4-(pyridin-4-yloxy)phenyl)-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;

((5R,6S)-5-((1S,3aS,4S,5S,7aR)-4-(aminomethyl)-1,7a-dimethyloctahydro-1H-inden-5-yl)-5-methyl-1-(4-(pyrimidin-5-yloxy)phenyl)-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol; and

((5R,6S)-5-((1S,3aS,4S,5S,7aR)-4-(aminomethyl)-1,7a-dimethyloctahydro-1H-inden-5-yl)-5-methyl-2-(4-(pyrimidin-5-yloxy)phenyl)-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol.

35. The compound of claim 32 wherein:

is a fused pyrazolyl substituted by aralkyl substituted by one or more substituents selected from halo, —R 10 —OR 11 or —R 10 —C(O)R 11 ;

R 1 is hydrogen;

R 2 is —R 6 —OR 7 ;

R 3 is —R 6 —OR 7 or —R 6 —N(R 8 ) 2 ;

R 4a is alkyl and R 4b is hydrogen;

R 5 is alkyl or R 5 is a direct bond to the carbon at C14;

each R 6 is independently selected from a direct bond or a straight or branched alkylene chain;

each R 7 is independently selected from hydrogen or alkyl;

each R 8 is independently selected from hydrogen or alkyl;

each R 10 is independently a direct bond or a straight or branched alkylene chain; and

each R 11 is independently hydrogen, alkyl, cycloalkyl or optionally substituted aryl.

36. The compound of claim 35 selected from:

((5R,6S)-5-((1S,3aS,4S,5S,7aR)-4-(aminomethyl)-1,7a-dimethyloctahydro-1H-inden-5-yl)-2-(4-methoxybenzyl)-5-methyl-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol; and

((5R,6S)-5-((1S,3aS,4S,5S,7aR)-4-(aminomethyl)-1,7a-dimethyloctahydro-1H-inden-5-yl)-1-(4-methoxybenzyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol.

37. A composition comprising a compound of claim 1 , or a stereoisomer, enantiomer or tautomer thereof or mixtures thereof, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

38. A method for treating inflammation and/or pain comprising administering an effective amount of a compound of claim 1 , or a stereoisomer, enantiomer or tautomer thereof or mixtures thereof, or a pharmaceutically acceptable salt or solvate thereof, or a composition of claim 37 to a mammal in need thereof.