Fused ring azadecalin glucocorticoid receptor modulators

1. A method of modulating a glucocorticoid receptor in a cell by contacting a glucocorticoid receptor with an effective amount of the compound of formula XI, wherein the compound of formula XI has the structure:

wherein

L 1 and L 2 are members independently selected from a bond and unsubstituted alkylene;

R 1 is a member selected from unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted heterocycloalkyl, —OR 1A , —NR 1C R 1D , —C(O)NR 1C R 1D , and —C(O)OR 1A , wherein

R 1A is a member selected from hydrogen, unsubstituted alkyl and unsubstituted heteroalkyl,

R 1C and R 1D are members independently selected from unsubstituted alkyl and unsubstituted heteroalkyl,

wherein R 1C and R 1D are optionally joined to form an unsubstituted ring with the nitrogen to which they are attached, wherein said ring optionally comprises an additional ring nitrogen;

R 2 has the formula:

wherein

R 2G is a member selected from hydrogen, halogen, unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, —CN, and —CF 3 ;

J is phenyl;

t is an integer from 0 to 5;

X is —S(O 2 )—; and

R 5 is phenyl optionally substituted with 1-5 R 5A groups, wherein

R 5A is a member selected from hydrogen, halogen, —OR 5A1 , —S(O 2 )NR 5A2 R 5A3 , —CN, and unsubstituted alkyl, wherein

R 5A1 is a member selected from hydrogen and unsubstituted alkyl, and

R 5A2 and R 5A3 are members independently selected from hydrogen and unsubstituted alkyl.

2. The method of claim 1 , wherein R 2G is a member selected from hydrogen, unsubstituted (C 1 -C 10 ) alkyl, unsubstituted 2-10 membered heteroalkyl, unsubstituted (C 3 -C 7 )cycloalkyl, and unsubstituted 3-7 membered heterocycloalkyl.

3. The method of claim 1 , wherein R 2G is a branched or unbranched (C 1 -C 10 )alkyl.

4. The method of claim 1 , wherein L 1 and L 2 are members independently selected from a bond and unsubstituted (C 1 -C 6 ) alkylene.

5. The method of claim 1 , wherein L 1 -R 1 is a member selected from methyl, —OR 1A , —C(O)OR 1A , CH 2 —OR 1A , (CH 2 ) 2 —OR 1A , NR 1C R 1D , —C(O)NR 1C R 1D ,—CH 2 —NR 1C R 1D , and —(CH 2 ) 2 —NR 1C R 1D .

6. The method of claim 5 , wherein L 1 -R 1 is a member selected from —CH 2 —OR 1A , and —CH 2 —NR 1C R 1D .

7. The method of claim 1 , wherein the compound has the formula

wherein,

L 1 -R 1 is a member selected from methyl, —OR 1A , —C(O)OR 1A , CH 2 —OR 1A , (CH 2 ) 2 —OR 1A , NR 1C R 1D , —C(O)NR 1C R 1D , —CH 2 —NR 1C R 1D , and —(CH 2 ) 2 —NR 1C R 1D .

8. The method of claim 1 , wherein the compound has the formula

9. The method of claim 1 , wherein the compound is selected from the group consisting of:

(S)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(S)-6-Benzenesulfonyl-1-(4-fluoro-phenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-1-1,2,6-triaza-cyclopenta[b]naphthalene;

(S)-1-(4-Fluoro-phenyl)-4a-methyl-6-(toluene-4-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(S)-1-(4-Trifluoromethyl-phenyl)-4a-methyl-6-(toluene-4-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(S)-1-(4-Fluoro-phenyl)-4a-methyl-6-(4-morpholin-4-yl-benzenesulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(S)-1-(4-Fluoro-phenyl)-4a-methyl-6-(4-methyl-3 ,4-dihydro-2H-benzo[1,4]oxazine-7-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

4-[(S)-1-(4-Fluoro-phenyl)-4a-methyl-1,4,4a,5,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-6-sulfonyl]-benzonitrile;

(S)-1-(4-Fluoro-phenyl)-6-(4-methoxy-benzenesulfonyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(S)-6-(4-Fluoro-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1 H-1,2,6-triaza-cyclopenta[b]naphthalene;

(S)-6-(2-Fluoro-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1 H-1,2,6-triaza-cyclopenta[b]naphthalene;

(S)-1-(4-Fluoro-phenyl)-4a-methyl-6-(toluene-2-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

4-[(S)-1-(4-Fluoro-phenyl)-4a-methyl-1,4,4a,5,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-6-sulfonyl]-phenylamine;

(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid methyl ester;

[(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-yl]-methanol;

[(R)-6-(4-Fluoro-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7, 8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-yl]-methanol;

[(R)-1-(4-Fluoro-phenyl)-6-(toluene-4-sulfonyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-yl]-methanol;

[(R)-6-Benzenesulfonyl-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-yl]-methanol;

(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-methoxymethyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-(2-methoxy-ethoxymethyl)-4,4a,5,6,7,8-hexahydro-1 H-1,2,6-triaza-cyclopenta[b]naphthalene;

(R)-6-(Benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-(2-hydroxy-ethoxymethyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(R)-6-(4-tert-Butyl-benzenesulfonyl)-4a-ethoxymethyl-1-(4-fluoro-phenyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-(3-methoxy-propoxymethyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

3-[(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl -1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-ylmethoxy]-propionitrile;

(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-(2-morpholin-4-yl-ethoxymethyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-(2-piperidin-1-yl-ethoxymethyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-(2-pyrrolidin-1-yl-ethoxymethyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(R)-6-(4-Fluoro-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-(2-methoxy-ethoxymethyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(R)-6-(4-Fluoro-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-methoxymethyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(R)-1-(4-Fluoro-phenyl)-4a-methoxymethyl-6-(toluene-4-sulfonyl)-4,4a,5,6,7, 8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(R)-1-(4-Fluoro-phenyl)-4a-(2-methoxy-ethoxymethyl)-6-(toluene-4-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(R)-6-Benzenesulfonyl-1-(4-fluoro-phenyl)-4a-(2-methoxy-ethoxymethyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(R)-6-Benzenesulfonyl-1-(4-fluoro-phenyl)-4a-methoxymethyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carbaldehyde;

[(S)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-ylmethyl]-dimethyl-amine;

(S)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-morpholin-4-ylmethyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(S)-6-(4-Trifluoromethyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-morpholin-4-ylmethyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(S)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-pyrrolidin-1-ylmethyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

([(S)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-ylmethyl]-ethyl-amine;

[(S)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[bnaphthalen-4a-ylmethyl]-diethyl-amine;

(S)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-piperidin-1-ylmethyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

[(S)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-ylmethyl]-(2-methoxy-ethyl)-amine;

(S)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-(4-methyl-piperazin-1-ylmethyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

N′-[(S)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-ylmethyl[-N,N-dimethyl-ethane-1,2-diamine;

N-[(S)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-ylmethyl]-N,N′,N′-trimethyl-ethane-1,2-diamine;

N′-[(S)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-ylmethyl]-N,N-dimethyl-propane-1,3-diamine;

N-[(S)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-ylmethyl]-N,N′,N′-trimethyl-propane-1,3-diamine;

[(S)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-ylmethyl]-(2-methoxy-ethyl -methyl-amine;

[(S)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-ylmethyl]-isopropyl-amine;

(S)-4a-Azetidin-1-ylmethyl-6-(4-tert-butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

Allyl-[(S)-6-(4-tert-butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-ylmethyl]-amine;

2-{[(S)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7-8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-ylmethyl]-amino}-ethanol;

[(S)-1-(4-Fluoro-phenyl)-6-(toluene-4-sulfonyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-ylmethyl]-dimethyl-amine;

(S)-1-(4-Fluoro-phenyl)-4a-pyrrolidin-1-ylmethyl-6-(toluene-4-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

[(S)-6-(4-Fluoro-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-ylmethyl]-dimethyl-amine;

(S)-6-(4-Fluoro-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-pyrrolidin-1-ylmethyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(S)-6-Benzenesulfonyl-1-(4-fluoro-phenyl)-4a-pyrrolidin-1-ylmethyl-4,4a,5,6,7, 8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(S)-6-Benzenesulfonyl-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-ylmethyl]dimethyl-amine;

(S)-6-Benzenesulfonyl-1-(4-fluoro-phenyl)-4a-morpholin-4-ylmethyl-4,4a,5,6,7, 8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

2-{[(S)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-ylmethyl]-methyl-amino}-ethanol;

4-[(S)-1-(4-Fluoro-phenyl)-4a-morpholin-4-ylmethyl-1,4,4a,5,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-6-sulfonyl]-benzonitrile;

[(S)-6-Benzenesulfonyl-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-ylmethyl]diethyl-amine;

Diethyl-[(S)-1-(4-fluoro-phenyl)-6-(4-methoxy-benzenesulfonyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-ylmethyl]-amine;

(S)-6-Benzenesulfonyl-1-(4-fluoro-phenyl)-4a-piperidin-1-ylmethyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(S)-1-(4-Fluoro-phenyl)-6-(4-methoxy-benzenesulfonyl)-4a-piperidin-1-ylmethyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(S)-1-(4-Fluoro-phenyl)-4a-morpholin-4-ylmethyl-6-(toluene-2-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(S)-6-(2-Fluoro-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-morpholin-4-ylmethyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid;

(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid benzylamide;

[(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-yl]-morpholin-4-yl-methanone;

[(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-yl]-piperidin-1-yl-methanone;

[(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-yl]-pyrrolidin-1-yl-methanone;

(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid ethylamide;

(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid dimethylamide;

1-[(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-yl]-ethanol;

1-[(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7, 8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-yl]-propan-1-ol;

[(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-yl]acetic acid methyl ester;

2-[(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-yl]-ethanol;

(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-(2-methoxy-ethyl)-4,4a,5,6,7, 8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene;

{2-[(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalen-4a-yl]-ethyl}-dimethylamine;

(R)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-(2-pyrrolidin-1-yl-ethyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene; and

(4aS,8aS)-6-(4-tert-Butyl-benzenesulfonyl)-1-(4-fluoro-phenyl)-4a-morpholin-4-ylmethyl-4,4a,5,6,7,8,8a,9-octahydro-1H-1,2,6-triazacyclopenta[b]naphthalene.