Indene derivatives useful in treating pain and inflammation

Abstract

Compounds of formula (I) wherein, R 1 , R 2 , R 3 , R 4a , R 4b and R 5 are described herein, or a stereoisomer, enantiomer or tautomer thereof or mixtures thereof, or a pharmaceutically acceptable salt or solvate thereof, are described herein, as well as other compounds. These compounds are useful in treating inflammation and/or pain. Compositions comprising a compound of the invention are also disclosed, as are methods of using the compounds to treat inflammation and/or pain.

1 . A pharmaceutical composition comprising from 0.1 mg to 250 mg of a compound of formula (I) and a pharmaceutically acceptable excipient: 
       
         
           
           
               
               
           
         
       
       wherein: 
       
         
           
           
               
               
           
         
         is an optionally substituted 5 to 14 membered fused N-heteroaryl, wherein the N-heteroaryl contains 1 to 13 carbon atoms and 1 to 6 nitrogen, oxygen or sulfur atoms; is fused to the cyclohexane; and optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, cyano, oxo, thioxo, nitro, thioxo, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, —R 21 —OR 20 , —R 21 —OC(O)—R 20 , —R 21 —N(R 20 ) 2 , —R 21 —C(O)R 20 , —R 21 —C(O)OR 20 , —R 21 —C(O)N(R 20 ) 2 , —R 21 —N(R 20 )C(O)OR 22 , —R 21 —N(R 20 )C(O)R 22 , —R 21 —N(R 20 )S(O) p R 22  where p is 1 to 2, —R 21 —N═C(OR 20 )R 20 , —R 21 —S(O) p OR 22  where p is 1 to 2, —R 21 —S(O) t R 22  where t is 0 to 2, and —R 21 —S(O) p N(R 20 ) 2  where p is 1 to 2; where each R 20  is independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl; each R 21  is independently a direct bond or a straight or branched alkylene chain; and each R 22  is alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl; 
         R 1  is hydrogen or —R 6 —OR 7 ; 
         R 2  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 3  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 4a  and R 4b  are each independently selected from hydrogen, alkyl or alkenyl; 
         or R 4a  is hydrogen, alkyl or alkenyl and R 4b  is a direct bond to the carbon to which R 1  is attached; 
         or 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, alkyl or optionally substituted heteroarylalkyl, wherein the heteroarylalkyl has a formula —R b R i ,
 wherein R b  is an alkylene chain containing 1 to 12 carbon atoms and is optionally substituted by one selected from the group consisting of alkyl, alkenyl, halo, cyano, nitro, aryl, cycloalkyl, heterocyclyl, heteroaryl, oxo, trimethylsilanyl, —OR 20 , —OC(O)—R 20 , —N(R 20 ) 2 , —C(O)R 20 , —C(O)OR 20 , —C(O)N(R 20 ) 2 , —N(R 20 )C(O)OR 22 , —N(R 20 )C(O)R 22 , —N(R 20 )S(O) p R 22  where p is 1 to 2, —S(O) p OR 22  where p is 1 to 2, —S(O) t R 22  where t is 0 to 2, and —S(O) p N(R 20 ) 2  where p is 1 to 2; where each R 20  is independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl; and each R 22  is alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl; and 
 R i  is a heteroaryl radical containing 1 to 13 carbon atoms and 1 to 6 nitrogen, oxygen or sulfur atoms; and optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, cyano, oxo, thioxo, nitro, thioxo, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, —R 21 —OR 20 , —R 21 —OC(O)— R 20 , —R 21 —N(R 20 ) 2 , —R 21 —C(O)R 20 , —R 21 —C(O)OR 20 , —R 21 —C(O)N(R 20 ) 2 , —R 21 —N(R 20 )C(O)OR 22 , —R 21 —N(R 20 )C(O)R 22 , —R 21 —N(R 20 )S(O) p R 22  where p is 1 to 2, —R 21 —N═C(OR 20 )R 20 , —R 21 —S(O) p OR 22  where p is 1 to 2, —R 21 —S(O) t R 22  where t is 0 to 2, and —R 21 —S(O) p N(R 20 ) 2  where p is 1 to 2; where each R 20  is independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl; each R 21  is independently a direct bond or a straight or branched alkylene chain; and each R 22  is alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl; 
 or two R 8 's, together with the nitrogen to which they are attached, form an optionally substituted N-heterocyclyl or an optionally substituted N-heteroaryl,
 wherein the N-heterocyclyl contains 2 to 12 carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, cyano, oxo, thioxo, nitro, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 21 —OR 20 , —R 21 —OC(O)—R 20 , —R 21 —N(R 20 ) 2 , —R 21 —C(O)R 20 , —R 21 —C(O)OR 20 , —R 21 —C(O)N(R 20 ) 2 , —R 21 —N(R 20 )C(O)OR 22 , —R 21 —N(R 20 )C(O)R 22 , —R 21 —N(R 20 )S(O) p R 22  (where p is 1 to 2), —R 21 —N═C(OR 20 )R 20 , —R 21 —S(O) p OR 22  (where p is 1 to 2), —R 21 —S(O) t R 22  (where t is 0 to 2), and —R 21 —S(O) p N(R 20 ) 2  (where p is 1 to 2) where each R 20  is independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl; each R 21  is independently a direct bond or a straight or branched alkylene chain; and each R 22  is alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl, and where the optional substituents on the heterocyclyl, heterocyclylalkyl, heteroaryl and heteroarylalkyl substitutents are selected from alkyl, halo or haloalkyl; 
 and wherein the N-heteroaryl contains 1 to 13 carbon atoms and 1 to 6 nitrogen, oxygen or sulfur atoms; and optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, cyano, oxo, thioxo, nitro, thioxo, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, —R 21 —OR 20 , —R 21 —OC(O)— R 20 , —R 21 —N(R 20 ) 2 , —R 21 —C(O)R 20 , —R 21 —C(O)OR 20 , —R 21 —C(O)N(R 20 ) 2 , —R 21 —N(R 20 )C(O)OR 22 , —R 21 —N(R 20 )C(O)R 22 , —R 21 —N(R 20 )S(O) p R 22  where p is 1 to 2, —R 21 —N═C(OR 20 )R 20 , —R 21 —S(O) p OR 22  where p is 1 to 2, —R 21 —S(O) t R 22  where t is 0 to 2, and —R 21 —S(O) p N(R 20 ) 2  where p is 1 to 2; where each R 20  is independently hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl; each R 21  is independently a direct bond or a straight or branched alkylene chain; and each R 22  is alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl; 
 
 
         or a stereoisomer, enantiomer or tautomer thereof or mixtures thereof, or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The pharmaceutical composition of  claim 1  wherein: 
       
         
           
           
               
               
           
         
         is a fused 5-membered N-heteroaryl optionally substituted by one or more substituents selected from alkyl, haloalkyl, —C(O)OR 7 , —N(R 8 ) 2 , —C(O)N(R 8 ) 2 , cycloalkyl, aryl, aralkyl or heteroaryl; 
         R 1  is hydrogen or —R 6 —OR 7 ; 
         R 2  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 3  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 4a  and R 4b  are each independently selected from hydrogen, alkyl or alkenyl; 
         or R 4a  is hydrogen, alkyl or alkenyl and R 4b  is a direct bond to the carbon to which R 1  is attached; 
         or 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, alkyl or optionally substituted heteroarylalkyl, 
         or two R 8 's, together with the nitrogen to which they are attached, form an optionally substituted N-heterocyclyl or an optionally substituted N-heteroaryl. 
       
     
     
         3 . The pharmaceutical composition of  claim 2  wherein: 
       
         
           
           
               
               
           
         
         is selected from optionally substituted pyrazolyl, optionally substituted oxazolyl, optionally substituted isoxazolyl, optionally substituted pyrrolyl, optionally substituted thiazolyl, or optionally substituted thiadiazolyl; 
         R 1  is hydrogen or —R 6 —OR 7 ; 
         R 2  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 3  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 4a  and R 4b  are each independently selected from hydrogen, alkyl or alkenyl; 
         or R 4a  is hydrogen, alkyl or alkenyl and R 4b  is a direct bond to the carbon to which R 1  is attached; 
         or 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, alkyl or optionally substituted heteroarylalkyl, 
         or two R 8 's, together with the nitrogen to which they are attached, form an optionally substituted N-heterocyclyl or an optionally substituted N-heteroaryl. 
       
     
     
         4 . The pharmaceutical composition of  claim 3  wherein: 
       
         
           
           
               
               
           
         
         is optionally substituted pyrazolyl; 
         R 1  is hydrogen or —R 6 —OR 7 ; 
         R 2  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 3  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 4a  and R 4b  are each independently selected from hydrogen, alkyl or alkenyl; 
         or R 4a  is hydrogen, alkyl or alkenyl and R 4b  is a direct bond to the carbon to which R 1  is attached; 
         or 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, alkyl or optionally substituted heteroarylalkyl, 
         or two R 8 's, together with the nitrogen to which they are attached, form an optionally substituted N-heterocyclyl or an optionally substituted N-heteroaryl. 
       
     
     
         5 . The pharmaceutical composition of  claim 4  wherein: 
       
         
           
           
               
               
           
         
         is optionally substituted pyrazolyl; 
         R 1  is hydrogen or —R 6 —OR 7 ; 
         R 2  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 3  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 4a  and R 4b  are each independently selected from hydrogen, alkyl or alkenyl; 
         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, alkyl or optionally substituted heteroarylalkyl, 
         or two R 8 's, together with the nitrogen to which they are attached, form an optionally substituted N-heterocyclyl or an optionally substituted N-heteroaryl. 
       
     
     
         6 . The pharmaceutical composition of  claim 3  wherein: 
       
         
           
           
               
               
           
         
         is optionally substituted isoxazolyl; 
         R 1  is hydrogen or —R 6 —OR 7 ; 
         R 2  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 3  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 4a  and R 4b  are each independently selected from hydrogen, alkyl or alkenyl; 
         or R 4a  is hydrogen, alkyl or alkenyl and R 4b  is a direct bond to the carbon to which R 1  is attached; 
         or 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, alkyl or optionally substituted heteroarylalkyl, 
         or two R 8 's, together with the nitrogen to which they are attached, form an optionally substituted N-heterocyclyl or an optionally substituted N-heteroaryl. 
       
     
     
         7 . The pharmaceutical composition of  claim 3  wherein: 
       
         
           
           
               
               
           
         
         is optionally substituted pyrrolyl; 
         R 1  is hydrogen or —R 6 —OR 7 ; 
         R 2  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 4a  and R 4b  are each independently selected from hydrogen, alkyl or alkenyl; 
         or R 4a  is hydrogen, alkyl or alkenyl and R 4b  is a direct bond to the carbon to which R 1  is attached; 
         or 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, alkyl or optionally substituted heteroarylalkyl, 
         or two R 8 's, together with the nitrogen to which they are attached, form an optionally substituted N-heterocyclyl or an optionally substituted N-heteroaryl. 
       
     
     
         8 . The pharmaceutical composition of  claim 3  wherein: 
       
         
           
           
               
               
           
         
         is optionally substituted thiazolyl; 
         R 1  is hydrogen or —R 6 —OR 7 ; 
         R 2  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 3  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 4a  and R 4b  are each independently selected from hydrogen, alkyl or alkenyl; 
         or R 4a  is hydrogen, alkyl or alkenyl and R 4b  is a direct bond to the carbon to which R 1  is attached; 
         or 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, alkyl or optionally substituted heteroarylalkyl, 
         or two R 8 's, together with the nitrogen to which they are attached, form an optionally substituted N-heterocyclyl or an optionally substituted N-heteroaryl. 
       
     
     
         9 . The pharmaceutical composition of  claim 3  wherein: 
       
         
           
           
               
               
           
         
         is optionally substituted thiadiazolyl; 
         R 1  is hydrogen or —R 6 —OR 7 ; 
         R 2  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 3  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 4a  and R 4b  are each independently selected from hydrogen, alkyl or alkenyl; 
         or R 4a  is hydrogen, alkyl or alkenyl and R 4b  is a direct bond to the carbon to which R 1  is attached; 
         or 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, alkyl or optionally substituted heteroarylalkyl, 
         or two R 8 's, together with the nitrogen to which they are attached, form an optionally substituted N-heterocyclyl or an optionally substituted N-heteroaryl. 
       
     
     
         10 . The pharmaceutical composition of  claim 3  wherein: 
       
         
           
           
               
               
           
         
         is optionally substituted oxazolyl; 
         R 1  is hydrogen or —R 6 —OR 7 ; 
         R 2  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 4a  and R 4b  are each independently selected from hydrogen, alkyl or alkenyl; 
         or R 4a  is hydrogen, alkyl or alkenyl and R 4b  is a direct bond to the carbon to which R 1  is attached; 
         or 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, alkyl or optionally substituted heteroarylalkyl, 
         or two R 8 's, together with the nitrogen to which they are attached, form an optionally substituted N-heterocyclyl or an optionally substituted N-heteroaryl. 
       
     
     
         11 . The pharmaceutical composition of  claim 3 , wherein the compound is selected from:
 ((5R,6S)-5-((1S,3aS,4S,5S,7aR)-4-(aminomethyl)-1-ethyl-7a-methyloctahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((5R,6S)-5-((4R,5S)-4-(hydroxymethyl)-1,1-dimethyl-2,3,4,5,6,7-hexahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((5R,6S)-5-((1S,3aS,4S,5S,7aR)-4-(hydroxymethyl)-1,7a-dimethyloctahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((5R,6S)-5-((4R,5S)-4-(aminomethyl)-1,1-dimethyl-2,3,4,5,6,7-hexahydro-1H-inden-5-yl)-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)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((3aS,4S,5S,7aS)-5-((5R,6S)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)-7a-methyloctahydro-1H-inden-4-yl)methanol;   (2R,4R,5S)-4-(hydroxymethyl)-5-((5R,6S)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)-1,1-dimethyl-2,3,4,5,6,7-hexahydro-1H-inden-2-ol;   ((5R,6S)-5-((3aS,4S,5S,7aS)-4-(aminomethyl)-7a-methyloctahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((5R,6S)-5-((1R,3aS,4S,5S,7aR)-4-(aminomethyl)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((5R,6S)-5-((1R,3aS,4S,5S,7aR)-4-((((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)amino)methyl)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((5R,6S)-5-((1R,3aS,4S,5S,7aS)-4-(aminomethyl)-7a-methyl-1-(prop-1-en-2-yl)octahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((1R,3aS,4S,5S,7aR)-5-((5R,6S)-6-(aminomethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-4-yl)methanamine;   ((1R,3aS,4S,5S,7aR)-5-((5R,6S)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-4-yl)methanol;   ((1R,3aS,4S,5S,7aS)-5-((5R,6S)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)-7a-methyl-1-(prop-1-en-2-yl)octahydro-1H-inden-4-yl)methanol;   ((5R,6S)-5-((1S,3aS,4S,5S,7aR)-1,7a-dimethyl-4-((methylamino)methyl)octahydro-1H-inden-5-yl)-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)-5-methyl-2-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-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)-1-cyclohexyl-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)-5-methyl-1-(pyridin-2-yl)-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-(pyridin-2-yl)-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-(tert-butyl)-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-(tert-butyl)-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)-5-methyl-1-neopentyl-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-neopentyl-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol;   ((5R,6S)-5-((3aR,6S,7R,7aS)-7-(hydroxymethyl)-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-6-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((5R,6S)-5-((3aR,6S,7R,7aS)-7-(aminomethyl)-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-6-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((5R,6S)-5-((3aS,6S,7R,7aS)-7-(aminomethyl)-3,3a-dimethyl-3a,4,5,6,7,7a-hexahydro-1H-inden-6-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)-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-1-phenyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   (5R,6S)-6-(hydroxymethyl)-5-((3aS,4R,5S,7aS)-4-(hydroxymethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid;   (5R,6S)-6-(hydroxymethyl)-5-((3aS,4R,5S,7aS)-4-(hydroxymethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazole-3-carboxamide;   ((5R,6S)-6-(hydroxymethyl)-5-((3aS,4R,5S,7aS)-4-(hydroxymethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)(piperidin-1-yl)methanone;   ((5R,6S)-6-(hydroxymethyl)-5-((3aS,4R,5S,7aS)-4-(hydroxymethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)(morpholino)methanone;   (2R,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-methyleneoctahydro-1H-inden-2-ol;   (2S,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-methyleneoctahydro-1H-inden-2-ol;   ((5R,6S)-5-((3aS,4R,5S,7aS)-4-((((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)amino)methyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-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)-3,5-dimethyl-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-3-(trifluoromethyl)-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)-3-(difluoromethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((5R,6S)-5-methyl-5-((3aS,4R,5S,7aS)-7a-methyl-1-methylene-4-(morpholinomethyl)octahydro-1H-inden-5-yl)-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((5R,6S)-5-methyl-5-((3aS,4R,5S,7aS)-7a-methyl-1-methylene-4-((4-methylpiperazin-1-yl)methyl)octahydro-1H-inden-5-yl)-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((5R,6S)-5-((3aS,4R,5S,7aS)-4-((1H-imidazol-1-yl)methyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((5R,6S)-5-((3aS,4R,5S,7aS)-4-((1H-pyrazol-1-yl)methyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((3aS,4R,5S,7aS)-5-((5R,6S)-6-(aminomethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)-7a-methyl-1-methyleneoctahydro-1H-inden-4-yl)methanamine;   ((5R,6S)-5-((3aS,4R,5S,7aS)-4-((1H-indol-1-yl)methyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((5R,6S)-5-((3aS,4R,5S,7aS)-4-((6-amino-9H-purin-9-yl)methyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((5R,6S)-5-((3aS,4R,5S,7aS)-4-((1H-benzo[d]imidazol-1-yl)methyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((5R,6S)-5-methyl-5-((3aS,4R,5S,7aS)-7a-methyl-1-methylene-4-(thiomorpholinomethyl)octahydro-1H-inden-5-yl)-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((5R,6S)-5-methyl-5-((3aS,4R,5S,7aS)-7a-methyl-1-methylene-4-(piperidin-1-ylmethyl)octahydro-1H-inden-5-yl)-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   (3aR,4R,5R,7aS)-7a-methyl-5-((5S,6S)-5-methyl-6-(morpholinomethyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl)-1-methyleneoctahydro-1H-inden-4-ol;   ((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-1-ethylidene-7a-methyloctahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((5R,6S)-5-((3aS,4R,5S,7aS,E)-1-ethylidene-4-(hydroxymethyl)-7a-methyloctahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((5R,6S)-5-methyl-5-((3aS,4R,5S,7aS)-7a-methyl-4-((methylamino)methyl)-1-methyleneoctahydro-1H-inden-5-yl)-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((5R,6S)-5-((3aS,4R,5S,7aS)-4-((dimethylamino)methyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-6-yl)methanol;   ((3aS,4R,5S,7aS)-7a-methyl-5-((5R,6S)-5-methyl-6-(piperidin-1-ylmethyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl)-1-methyleneoctahydro-1H-inden-4-yl)methanol;   ((3aS,4R,5S,7aS)-7a-methyl-5-((5R,6S)-5-methyl-6-(morpholinomethyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl)-1-methyleneoctahydro-1H-inden-4-yl)methanol;   ((3aS,4R,5S,7aS)-7a-methyl-5-((5R,6S)-5-methyl-6-(thiomorpholinomethyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl)-1-methyleneoctahydro-1H-inden-4-yl)methanol;   ((3aS,4R,5S,7aS)-7a-methyl-5-((5R,6S)-5-methyl-6-((4-methylpiperazin-1-yl)methyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl)-1-methyleneoctahydro-1H-inden-4-yl)methanol;   ((3aS,4R,5S,7aS)-7a-methyl-5-((5R,6S)-5-methyl-6-(piperidin-1-ylmethyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl)-1-methyleneoctahydro-1H-inden-4-yl)methanamine;   ((3aS,4R,5S,7aS)-7a-methyl-5-((5R,6S)-5-methyl-6-(morpholinomethyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl)-1-methyleneoctahydro-1H-inden-4-yl)methanamine;   ((3aS,4R,5S,7aS)-7a-methyl-5-((5R,6S)-5-methyl-6-(thiomorpholinomethyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl)-1-methyleneoctahydro-1H-inden-4-yl)methanamine;   ((3aS,4R,5S,7aS)-7a-methyl-5-((5R,6S)-5-methyl-6-((4-methylpiperazin-1-yl)methyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl)-1-methyleneoctahydro-1H-inden-4-yl)methanamine;   ((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-2-(tert-butyl)-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-(tert-butyl)-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-dimethyl-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-cyclohexyl-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-(pyridin-2-yl)-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-benzyl-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-(pyridin-3-yl)-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-1-neopentyl-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-neopentyl-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol;   ((3aS,4R,5S,7aS)-5-((5R,6S)-6-(aminomethyl)-5-methyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)-7a-methyl-1-methyleneoctahydro-1H-inden-4-yl)methanol;   (3aR,4R,5R,7aS)-7a-methyl-5-((5S,6S)-5-methyl-6-((4-methylpiperazin-1-yl)methyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl)-1-methyleneoctahydro-1H-inden-4-ol;   ((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-5-methyl-2-phenyl-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-(pyridin-2-yl)-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-dimethyl-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-cyclohexyl-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-benzyl-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-(pyridin-3-yl)-4,5,6,7-tetrahydro-2H-indazol-6-yl)methanol;   (3aR,4R,5R,7aS)-5-((5S,6S)-6-(hydroxymethyl)-5-methyl-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)-7a-methyl-1-methyleneoctahydro-1H-inden-4-ol;   (3aR,4R,5R,7aS)-5-((5S,6S)-6-(hydroxymethyl)-5-methyl-2-(pyrazin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)-7a-methyl-1-methyleneoctahydro-1H-inden-4-ol;   (3aR,4R,5R,7aS)-5-((5S,6S)-6-(hydroxymethyl)-5-methyl-2-(pyrimidin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)-7a-methyl-1-methyleneoctahydro-1H-inden-4-ol;   ((5R,6S)-5-((4R,5S)-4-(aminomethyl)-1,1-dimethyl-2,3,4,5,6,7-hexahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydrobenzo[d]isoxazol-6-yl)methanol;   ((1R,3aS,4S,5S,7aR)-5-((5R,6S)-6-(hydroxymethyl)-5-methyl-4,5,6,7-tetrahydrobenzo[d]isoxazol-5-yl)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-4-yl)methanol;   ((5R,6S)-5-((3aS,6S,7R,7aS)-7-(aminomethyl)-3,3a-dimethyl-3a,4,5,6,7,7a-hexahydro-1H-inden-6-yl)-5-methyl-4,5,6,7-tetrahydrobenzo[d]isoxazol-6-yl)methanol;   ((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydrobenzo[c]isoxazol-6-yl)methanol;   ((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-5-methyl-4,5,6,7-tetrahydro-1H-indol-6-yl)methanol;   ((1R,3aS,4S,5S,7aR)-5-((5S,6R)-2-amino-5-(hydroxymethyl)-6-methyl-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-4-yl)methanol;   ((5S,6R)-2-amino-6-((1R,3aS,4S,5S,7aR)-4-(aminomethyl)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-5-yl)-6-methyl-4,5,6,7-tetrahydrobenzo[d]thiazol-5-yl)methanol;   ((5S,6R)-6-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-2,6-dimethyl-4,5,6,7-tetrahydrobenzo[d]thiazol-5-yl)methanol;   ((5S,6R)-2-amino-6-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-6-methyl-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)methanol;   ((1R,3aS,4S,5S,7aR)-5-((5S,6R)-5-(hydroxymethyl)-6-methyl-4,5,6,7-tetrahydrobenzo[d][1,2,3]thiadiazol-6-yl)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-4-yl)methanol;   ((5S,6R)-6-((1R,3aS,4S,5S,7aR)-4-(aminomethyl)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-5-yl)-6-methyl-4,5,6,7-tetrahydrobenzo[d][1,2,3]thiadiazol-5-yl)methanol;   ((3aS,4R,5S,7aS)-5-((5R,6S)-6-(hydroxymethyl)-2,5-dimethyl-4,5,6,7-tetrahydrobenzo[d]oxazol-5-yl)-7a-methyl-1-methyleneoctahydro-1H-inden-4-yl)methanol; or   ((5R,6S)-5-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-2,5-dimethyl-4,5,6,7-tetrahydrobenzo[d]oxazol-6-yl)methanol.   
     
     
         12 . The pharmaceutical composition of  claim 1  wherein: 
       
         
           
           
               
               
           
         
         is fused 6-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 , cycloalkyl, aryl, aralkyl or heteroaryl; 
         R 1  is hydrogen or —R 6 —OR 7 ; 
         R 2  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 3  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 4a  and R 4b  are each independently selected from hydrogen, alkyl or alkenyl; 
         or R 4a  is hydrogen, alkyl or alkenyl and R 4b  is a direct bond to the carbon to which R 1  is attached; 
         or 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, alkyl or optionally substituted heteroarylalkyl, 
         or two R 8 's, together with the nitrogen to which they are attached, form an optionally substituted N-heterocyclyl or an optionally substituted N-heteroaryl. 
       
     
     
         13 . The pharmaceutical composition of  claim 12  wherein: 
       
         
           
           
               
               
           
         
         is selected from optionally substituted pyrazinyl or optionally substituted pyrimidinyl; 
         R 1  is hydrogen or —R 6 —OR 7 ; 
         R 2  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 3  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 4a  and R 4b  are each independently selected from hydrogen, alkyl or alkenyl; 
         or R 4a  is hydrogen, alkyl or alkenyl and R 4b  is a direct bond to the carbon to which R 1  is attached; 
         or 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, alkyl or optionally substituted heteroarylalkyl, 
         or two R 8 's, together with the nitrogen to which they are attached, form an optionally substituted N-heterocyclyl or an optionally substituted N-heteroaryl. 
       
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein the compound is selected from:
 ((1R,3aS,4S,5S,7aR)-5-((6R,7S)-7-(hydroxymethyl)-6-methyl-5,6,7,8-tetrahydroquinoxalin-6-yl)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-4-yl)methanol;   ((6S,7R)-7-((1R,3aS,4S,5S,7aR)-4-(aminomethyl)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-5-yl)-7-methyl-5,6,7,8-tetrahydroquinoxalin-6-yl)methanol;   ((3aS,4R,5S,7aS)-5-((6R,7S)-7-(hydroxymethyl)-6-methyl-5,6,7,8-tetrahydroquinoxalin-6-yl)-7a-methyl-1-methyleneoctahydro-1H-inden-4-yl)methanol;   ((6S,7R)-7-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-7-methyl-5,6,7,8-tetrahydroquinoxalin-6-yl)methanol;   ((6R,7S)-2-amino-6-((1R,3aS,4S,5S,7aR)-4-(hydroxymethyl)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-5-yl)-6-methyl-5,6,7,8-tetrahydroquinazolin-7-yl)methanol;   ((6R,7S)-2-amino-6-((1R,3aS,4S,5S,7aR)-4-(aminomethyl)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-5-yl)-6-methyl-5,6,7,8-tetrahydroquinazolin-7-yl)methanol;   ((1R,3aS,4S,5S,7aR)-5-((6R,7S)-7-(hydroxymethyl)-2,6-dimethyl-5,6,7,8-tetrahydroquinazolin-6-yl)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-4-yl)methanol;   ((6R,7S)-6-((1R,3aS,4S,5S,7aR)-4-(aminomethyl)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-5-yl)-2,6-dimethyl-5,6,7,8-tetrahydroquinazolin-7-yl)methanol;   ((1R,3aS,4S,5S,7aR)-5-((6R,7S)-7-(hydroxymethyl)-6-methyl-5,6,7,8-tetrahydroquinazolin-6-yl)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-4-yl)methanol;   ((6R,7S)-6-((1R,3aS,4S,5S,7aR)-4-(aminomethyl)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-5-yl)-6-methyl-5,6,7,8-tetrahydroquinazolin-7-yl)methanol;   ((6R,7S)-2-amino-6-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-6-methyl-5,6,7,8-tetrahydroquinazolin-7-yl)methanol;   ((6R,7S)-6-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-2,6-dimethyl-5,6,7,8-tetrahydroquinazolin-7-yl)methanol;   ((6R,7S)-6-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-6-methyl-5,6,7,8-tetrahydroquinazolin-7-yl)methanol;   ((6R,7S)-2-amino-6-((3aS,4R,5S,7aS)-4-(hydroxymethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-6-methyl-5,6,7,8-tetrahydroquinazolin-7-yl)methanol;   ((3aS,4R,5S,7aS)-5-((6R,7S)-7-(hydroxymethyl)-2,6-dimethyl-5,6,7,8-tetrahydroquinazolin-6-yl)-7a-methyl-1-methyleneoctahydro-1H-inden-4-yl)methanol; or   ((3aS,4R,5S,7aS)-5-((6R,7S)-7-(hydroxymethyl)-6-methyl-5,6,7,8-tetrahydroquinazolin-6-yl)-7a-methyl-1-methyleneoctahydro-1H-inden-4-yl)methanol.   
     
     
         15 . The pharmaceutical composition of  claim 1  wherein: 
       
         
           
           
               
               
           
         
         is an optionally substituted fused 13-membered N-heteroaryl; 
         R 1  is hydrogen or —R 6 —OR 7 ; 
         R 2  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 3  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 4a  and R 4b  are each independently selected from hydrogen, alkyl or alkenyl; 
         or R 4a  is hydrogen, alkyl or alkenyl and R 4b  is a direct bond to the carbon to which R 1  is attached; 
         or 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, alkyl or optionally substituted heteroarylalkyl, 
         or two R 8 's, together with the nitrogen to which they are attached, form an optionally substituted N-heterocyclyl or an optionally substituted N-heteroaryl. 
       
     
     
         16 . The pharmaceutical composition of  claim 15  wherein: 
       
         
           
           
               
               
           
         
         is optionally substituted benzo[4,5]imidazo[1,2-a]pyrimidinyl; 
         R 1  is hydrogen or —R 6 —OR 7 ; 
         R 2  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 3  is —R 6 —OR 7  or —R 6 —N(R 8 ) 2 ; 
         R 4a  and R 4b  are each independently selected from hydrogen, alkyl or alkenyl; 
         or R 4a  is hydrogen, alkyl or alkenyl and R 4b  is a direct bond to the carbon to which R 1  is attached; 
         or 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, alkyl or optionally substituted heteroarylalkyl, 
         or two R 8 's, together with the nitrogen to which they are attached, form an optionally substituted N-heterocyclyl or an optionally substituted N-heteroaryl. 
       
     
     
         17 . The pharmaceutical composition of  claim 15 , wherein the compound is selected from:
 ((3aS,4R,5S,7aS)-5-((2R,3S)-3-(hydroxymethyl)-2-methyl-1,2,3,4-tetrahydrobenzo[4,5]imidazo[2,1-b]quinazolin-2-yl)-7a-methyl-1-methyleneoctahydro-1H-inden-4-yl)methanol; or   ((2R,3S)-2-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-2-methyl-1,2,3,4-tetrahydrobenzo[4,5]imidazo[2,1-b]quinazolin-3-yl)methanol.