IP Library Granted Patent US 8,598,154
Granted Patent B2
US 8,598,154 · App. 13/218,809 · Granted Dec 3, 2013

Pyridyl-amine fused azadecalin modulators

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Quick Facts
Patent No.
US 8,598,154
App. No.
13/218,809
Granted
Dec 3, 2013
Kind
B2
Abstract

The present invention provides a novel class of pyridyl-amine fused azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators.

Claims (107)

1. A compound having the formula:

wherein

L 1 is selected from the group consisting of a bond, —C(O)O—C 0-6 alkylene, C 1-6 alkylene and C 1-6 heteroalkylene;

R 1 is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, C 3-8 cycloalkyl, C 3-8 heterocycloalkyl, aryl, heteroaryl, —OR 1a , NR 1c R 1d , and —C(O)NR 1c R 1d , wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl groups are optionally substituted with hydrogen, C 1-6 alkyl, hydroxy and C 1-6 alkoxy;

each R 1a is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, C 3-8 cycloalkyl, C 1-6 alkylC 3-8 cycloalkyl, C 3-8 heterocycloalkyl, C 1-6 alkylC 3-8 heterocycloalkyl, aryl, C 1-6 alkylaryl, heteroaryl and C 1-6 alkylheteroaryl;

each of R 1c and R 1d are independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 heteroalkyl, C 3-8 cycloalkyl, C 3-8 heterocycloalkyl, aryl, and heteroaryl;

alternatively, R 1c and R 1d are combined to form a C 3-8 heterocycloalkyl having from 1 to 3 heteroatoms each independently selected from the group consisting of N, O and S, and optionally substituted with 1 to 3 groups each independently selected from the group consisting of hydrogen, C 1-6 alkyl, hydroxy and C 1-6 alkoxy;

ring J is a heteroaryl ring having from 5 to 6 ring members and from 1 to 3 heteroatoms each independently selected from the group consisting of N, O and S, wherein at least one heteroatom is N;

each of R 2 and R 3 are independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, C 3-8 cycloalkyl, C 3-8 heterocycloalkyl, aryl and heteroaryl;

R 4 is selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 heteroalkyl, C 3-8 cycloalkyl, C 3-8 heterocycloalkyl, aryl and heteroaryl;

alternatively R 2 is combined with R 3 or R 4 to form a C 3-8 heterocycloalkyl having from 1 to 3 heteroatoms each independently selected from the group consisting of N, O and S, and optionally substituted with 1 to 3 R 2a groups, wherein each R 2a is independently selected from the group consisting of hydrogen, C 1-6 alkyl, halogen, C 1-6 haloalkyl, hydroxy, C 1-6 alkoxy, C 1-6 haloalkoxy, nitro, cyano, C 3-8 cycloalkyl, C 3-8 heterocycloalkyl, aryl and heteroaryl;

subscript n is 0 or 1;

each R 5a is independently selected from the group consisting of hydrogen, halogen, —OR 5a1 , —NR 5a2 R 5a3 , —S(O 2 )NR 5a2 R 5a3 , —CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, C 3-8 cycloalkyl, C 3-8 heterocycloalkyl, aryl, and heteroaryl;

each of R 5a1 , R 5a2 and R 5a3 are independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 heteroalkyl, C 3-8 cycloalkyl, C 3-8 heterocycloalkyl, aryl, and heteroaryl;

wherein when R 4 is hydrogen, subscript n is 1;

and salts and isomers thereof.

2. The compound of claim 1 , having the formula:

wherein

each of R 2 and R 3 is independently selected from the group consisting of H and C 1-6 alkyl;

alternatively, R 2 is combined with R 3 to form a C 3-8 heterocycloalkyl having from 1 to 3 heteroatoms each independently selected from the group consisting of N, O and S, and optionally substituted with 1 to 3 R 2a groups, wherein each R 2a is independently selected from the group consisting of hydrogen, C 1-6 alkyl, halogen, C 1-6 haloalkyl, hydroxy, C 1-6 alkoxy, C 1-6 haloalkoxy, nitro, cyano, C 3-8 cycloalkyl, C 3-8 heterocycloalkyl, aryl and heteroaryl; and

R 5a is halogen.

3. The compound of claim 1 , wherein

L 1 is selected from the group consisting of —C(O)O—, —C(O)O—C 1-6 alkylene, and C 1-6 alkylene;

R 1 is selected from the group consisting of C 1-6 alkyl, C 3-8 cycloalkyl, C 3-8 heterocycloalkyl, heteroaryl, and —OR 1a , wherein the cycloalkyl, heterocycloalkyl and heteroaryl groups are optionally substituted with hydrogen, C 1-6 alkyl, hydroxy and C 1-6 alkoxy; and

each R 1a is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, C 3-8 cycloalkyl, C 1-6 alkylC 3-8 cycloalkyl, C 3-8 heterocycloalkyl, C 1-6 alkylC 3-8 heterocycloalkyl, aryl, C 1-6 alkylaryl, heteroaryl and C 1-6 alkylheteroaryl.

4. The compound of claim 3 , wherein the group L 1 -R 1 is selected from the group consisting of —CH 2 R 1 , —CH 2 OR 1a , —C(O)OR 1 and —C(O)O—CH 2 —R 1 .

5. The compound of claim 4 , wherein the group L 1 -R 1 is selected from the group consisting of methoxymethyl, ethoxymethyl, (difluoromethoxy)methyl, (cyclopropylmethoxy)methyl, (2-methoxyethoxy)methyl, (2-hydroxyethoxy)methyl, (oxazol-2-ylmethoxy)methyl, ((5-methylisoxazol-3-yl)methoxy)methyl, N-(2-hydroxyethyl)-N-methyl-aminomethyl, (3-hydroxy-pyrrolidin-1-yl)methyl, methyl carboxylate, ethyl carboxylate, isopropyl carboxylate, cyclobutyl carboxylate, cyclopropylmethyl carboxylate, cyclobutylmethyl carboxylate, (3-hydroxycyclobutyl)methyl carboxylate, (3-methyloxetan-3-yl)methyl carboxylate, 2-hydroxyethyl carboxylate, 2-(dimethylamino)ethyl carboxylate, and (5-methylisoxazol-3-yl)methyl carboxylate.

6. The compound of claim 1 , wherein ring J is selected from the group consisting of pyrrole, imidazole, pyrazole, thiazole, isothiazole, oxazole, isoxazole, pyridine, pyrazine, pyrimidine and pyridazine.

7. The compound of claim 1 , wherein ring J is selected from the group consisting of pyrid-2-yl, pyrid-3-yl and pyrid-4-yl.

8. The compound of claim 1 , having the formula:

9. The compound of claim 1 , wherein R 2 is combined with R 3 to form a C 3-8 heterocycloalkyl having from 1 to 2 heteroatoms each independently selected from the group consisting of N and O, and optionally substituted with 1 to 3 R 2a groups, wherein each R 2a is independently selected from the group consisting of C 1-6 alkyl, halogen, C 1-6 haloalkyl, hydroxy, C 1-6 alkoxy and C 1-6 haloalkoxy.

10. The compound of claim 9 , wherein R 2 is combined with R 3 to form a C 3-8 heterocycloalkyl selected from the group consisting of azetidine, pyrrolidine, imidazolidine, pyrazolidine, oxazolidine, isoxazolidine, piperidine, piperazine, morpholine, azepane, homopiperazine, azacyclooctane, quinuclidine, 1,4-diazabicyclo[2.2.2]octane and 2-oxa-5-azabicyclo[2.2.1]heptane, each optionally substituted with 1 R 2a group selected from the group consisting of halogen and hydroxy.

11. The compound of claim 10 , wherein R 2 is combined with R 3 to form a C 3-8 heterocycloalkyl selected from the group consisting of azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, morpholin-1-yl and 2-oxa-5-azabicyclo[2.2.1]heptan-5-yl, wherein the azetidin-1-yl, pyrrolidin-1-yl, and piperidin-1-yl are each optionally substituted with 1 R 2a group selected from the group consisting of F and hydroxy.

12. The compound of claim 11 , wherein R 2 is combined with R 3 to form a C 3-8 heterocycloalkyl selected from the group consisting of azetidin-1-yl, 3-fluoro-azetidin-1-yl, 3-hydroxy-azetidin-1-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoro-pyrrolidin-1-yl, morpholin-1-yl and 2-oxa-5-azabicyclo[2.2.1]heptan-5-yl.

13. The compound of claim 1 , wherein R 5a is F.

14. The compound of claim 1 , having the formula:

15. The compound of claim 1 , having the formula:

16. The compound of claim 1 , wherein subscript n is 0.

17. The compound of claim 1 , selected from the group consisting of:

(R)-4a-Ethoxymethyl-1-(4-fluorophenyl)-6-[[6-(4-morpholinyl)-3-pyridinyl]sulfonyl]-1,4,7,8-tetrahydro-1,2,6-triazacyclopenta[b]naphthalene,

(R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-ylpyridine-3-sulfonyl)-1,4,5,6,7,8-hexahydro-1,2,6-triazacyclopenta[b]naphthalene-4a-carboxylic acid methyl ester,

[(R)-1-(4-Fluorophenyl)-6-[[6-(4-morpholinyl)-3-pyridinyl]sulfonyl]-1,4,7,8-tetrahydro-1,2,6-triazacyclopenta[b]naphthalen-4a-yl]methanol,

(R)-4a-Ethoxymethyl-1-(4-fluorophenyl)-6-[[3-pyridinyl]sulfonyl]-1,4,7,8-tetrahydro-1,2,6-triazacyclopenta[b]naphthalene,

(R)-4a-Ethoxymethyl-1-(4-fluorophenyl)-6-[[2H-pyrido[3.2-b]-1,4-oxazin-7-yl]sulfonyl]-1,4,7,8-tetrahydro-1,2,6-triazacyclopenta[b]naphthalene,

(R)-4a-Ethoxymethyl-1-(4-fluorophenyl)-6-[[6-(1-pyrrolidinyl)-3-pyridinyl]sulfonyl]-1,4,7,8-tetrahydro-1,2,6-triazacyclopenta[b]naphthalene,

(R)-1-(4-Fluorophenyl)-4a-methoxymethyl-6-[[6-(1-pyrrolidinyl)-3-pyridinyl]sulfonyl]-1,4,7,8-tetrahydro-1,2,6-triazacyclopenta[b]naphthalene,

(R)-6-[[6-(1-Azetidinyl)-3-pyridinyl]sulfonyl]-4a-ethoxymethyl-1-(4-fluorophenyl)-1,4,7,8-tetrahydro-1,2,6-triazacyclopenta[b]naphthalene,

(R)-4a-Ethoxymethyl-1-(4-fluorophenyl)-6-[[6-methylamino-3-pyridinyl]sulfonyl]-1,4,7,8-tetrahydro-1,2,6-triazacyclopenta[b]naphthalene,

(R)-6-[[6-Dimethylamino-3-pyridinyl]sulfonyl]-4a-ethoxymethyl-1-(4-fluorophenyl)-1,4,7,8-tetrahydro-1,2,6-triazacyclopenta[b]naphthalene,

(R)-1-(4-Fluorophenyl)-4a-methoxymethyl-6-[[6-methylamino-3-pyridinyl]sulfonyl]-1,4,7,8-tetrahydro-1,2,6-triazacyclopenta[b]naphthalene,

(R)-6-[[6-Dimethylamino-3-pyridinyl]sulfonyl]-1-(4-fluorophenyl)-4a-methoxymethyl-1,4,7,8-tetrahydro-1,2,6-triazacyclopenta[b]naphthalene,

(R)-6-[[6-(1-Azetidinyl)-3-pyridinyl]sulfonyl]-1-(4-fluorophenyl)-4a-methoxymethyl-1,4,7,8-tetrahydro-1,2,6-triazacyclopenta[b]naphthalene,

(R)-1-(4-Fluorophenyl)-4a-methoxymethyl-6-(5-morpholin-4-ylpyridine-3-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triazacyclopenta[b]naphthalene,

(R)-6-(5-Azetidin-1-ylpyridine-3-sulfonyl)-1-(4-fluorophenyl)-4a-methoxymethyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triazacyclopenta[b]naphthalene,

(R)-1-(4-Fluorophenyl)-4a-methoxymethyl-6-(6-morpholin-4-yl-pyridine-3-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triazacyclopenta[b]naphthalene,

(R)-4a-Difluoromethoxymethyl-1-(4-fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triazacyclopenta[b]naphthalene,

(R)-6-(6-Azetidin-1-yl-pyridine-3-sulfonyl)-1-(4-fluorophenyl)-4a-(oxazol-2-ylmethoxymethyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triazacyclopenta[b]naphthalene,

(R)-6-(6-Azetidin-1-ylpyridine-3-sulfonyl)-4a-difluoromethoxymethyl-1-(4-fluorophenyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triazacyclopenta[b]naphthalene,

(R)-1-(4-Fluorophenyl)-4a-methoxymethyl-6-[[6-(1-piperazinyl)-3-pyridinyl]sulfonyl]-1,4,7,8-tetrahydro-1,2,6-triazacyclopenta[b]naphthalene,

(R)-1-(4-Fluorophenyl)-4a-methoxymethyl-6-[[6-(1-(4-methylpiperazinyl))-3-pyridinyl]sulfonyl]-1,4,7,8-tetrahydro-1,2,6-triazacyclopenta[b]naphthalene,

(R)-1-(4-Fluorophenyl)-6-[6-((R)-3-fluoropyrrolidin-1-yl)-pyridine-3-sulfonyl]-4a-methoxymethyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene,

(R)-1-{5-[(R)-1-(4-Flurophenyl)-4a-methoxymethyl-1,4,4a,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-6-sulfonyl]-pyridin-2-yl}-pyrrolidin-3-ol,

(S)-1-{5-[(R)-1-(4-Flurophenyl)-4a-methoxymethyl-1,4,4a,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-6-sulfonyl]-pyridin-2-yl}-pyrrolidin-3-ol,

(R)-1-(4-Fluorophenyl)-4a-methoxymethyl-6-[(1S,4S)-6-(2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl)pyridine-3-sulfonyl]-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene,

(R)-1-(4-Fluorophenyl)-4a-methoxymethyl-6-(6-trifluoromethylpyridine-3-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene,

(R)-4a-Cyclopropylmethoxymethyl-1-(4-fluorophenyl)-6-(6-pyrrolidin-1-yl-pyridine-3-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene,

(R)-4a-Cyclopropylmethoxymethyl-1-(4-fluorophenyl)-6-(6-((R)-3-fluoro-pyrrolidin-1-yl)-pyridine-3-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene,

(R)-4a-Cyclopropylmethoxymethyl-1-(4-fluorophenyl)-6-(6-((S)-3-fluoropyrrolidin-1-yl)-pyridine-3-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene,

(R)-1-{5-[(R)-4a-Cyclopropylmethoxymethyl-1-(4-fluorophenyl)-1,4,4a,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-6-sulfonyl]pyridine-2-yl}-pyrrolidine-3-ol,

(S)-1-{5-[(R)-4a-Cyclopropylmethoxymethyl-1-(4-fluorophenyl)-1,4,4a,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-6-sulfonyl]pyridine-2-yl}-pyrrolidine-3-ol,

(R)-4a-Cyclopropylmethoxymethyl-6-[6-(3-fluoroazetin-1-yl)-pyridine-3-sulfonyl]-1-(4-fluorophenyl)-1,4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene,

1-{5-[(R)-4a-Cyclopropylmethoxymethyl-1-(4-fluorophenyl)-1,4,4a,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-6-sulfonyl]-pyridin-2-yl}-azetidin-3-ol,

(R)-4a-Cyclopropylmethoxymethyl-1-(4-fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene,

(R)-1-(4-Fluorophenyl)-6-[6-((R)-3-fluoropyrrolidin-1-yl)-pyridine-3-sulfonyl]-4a-(2-methoxyethoxymethyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene,

2-{(R)-1-(4-Fluorophenyl)-6-[6-((R)-3-fluoropyrrolidin-1-yl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-ylmethoxy}ethanol,

(R)-1-(4-Fluorophenyl)-6-[6-((R)-3-fluoropyrrolidin-1-yl)-pyridine-3-sulfonyl]-4a-(5-methyl-isoxazol-3-ylmethoxymethyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene,

1-{5-[(R)-1-(4-Fluorophenyl)-4a-methoxymethyl-1,4,4a,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-6-sulfonyl]-pyridin-3-yl}-azetidin-3-ol,

(R)-6-[5-(3-Fluoroazetidin-1-yl)-pyridine-3-sulfonyl]-1-(4-fluorophenyl)-4a-methoxymethyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene,

(R)-1-{5-[(R)-1-(4-Fluorophenyl)-4a-methoxymethyl-1,4,4a,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-6-sulfonyl]pyridine-3-yl}-pyrrolidine-3-ol,

(S)-1-{5-[(R)-1-(4-Fluorophenyl)-4a-methoxymethyl-1,4,4a,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-6-sulfonyl]pyridine-3-yl}-pyrrolidine-3-ol,

(R)-1-(4-Fluorophenyl)-6-[5-((R)-3-fluoropyrrolidin-1-yl)-pyridine-3-sulfonyl]-4a-methoxymethyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene,

(R)-1-(4-Fluorophenyl)-6-[5-((S)-3-fluoropyrrolidin-1-yl)-pyridine-3-sulfonyl]-4a-methoxymethyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene,

(R)-1-(4-Fluorophenyl)-4a-methoxymethyl-6-(2-pyrrolidin-1-yl-pyridine-4-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene,

(R)-1-{4-[(R)-1-(4-Fluorophenyl)-4a-methoxymethyl-1,4,4a,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-6-sulfonyl]-pyridin-2-yl}-pyrrolidin-3-ol,

(S)-1-{4-KR)-1-(4-Fluorophenyl)-4a-methoxymethyl-1,4,4a,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-6-sulfonyl]-pyridin-2-yl}-pyrrolidin-3-ol,

2-{[(S)-1-(4-Fluorophenyl)-6-[6-morpholin-4-yl-pyridine-3-sulfonyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-ylmethyl]-methyl-amino}-ethanol,

(S)-1-{(S)-1-(4-Fluorophenyl)-6-[6-((R)-3-hydroxy-pyrrolidin-3-ol)-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-ylmethyl}-pyrrolidin-3-ol,

(S)-1-{(S)-1-(4-Fluorophenyl)-6-[6-((R)-3-fluoro-pyrrolidin-1-yl)-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-ylmethyl}-pyrrolidin-3-ol,

(R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid ethyl ester,

(R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid isopropyl ester,

(R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid cyclobutyl ester,

(R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid cyclopropylmethyl ester,

(R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid cyclobutylmethyl ester,

(R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid 3-hydroxycyclobutylmethyl ester,

(R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid 3-methyloxetan-3-ylmethyl ester,

(R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid 2-hydroxethyl ester,

(R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid 2-dimethylaminoethyl ester,

(R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid 5-methylisoxazol-3-ylmethyl ester,

(R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid cyclopropylmethyl ester,

(R)-1-(4-Fluorophenyl)-6-(6-methoxy pyridine-3-sulfonyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid cyclobutylmethyl ester,

(R)-1-(4-Fluorophenyl)-6-[6-((R)-3-fluoropyrrolidin-1-yl)-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid 5-methylisoxazol-3-ylmethyl ester,

(R)-1-(4-Fluorophenyl)-6-[6-((R)-3-fluoropyrrolidin-1-yl)-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid 3-hydroxy cyclobutylmethyl ester,

(S)-1-[(S)-1-(4-Fluorophenyl)-6-[6-morpholin-4-yl-pyridine-3-sulfonyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-ylmethyl]-pyrrolidin-3-ol,

(R)-1-[(S)-1-(4-Fluorophenyl)-6-[6-morpholin-4-yl-pyridine-3-sulfonyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-ylmethyl]-pyrrolidin-3-ol, or

(R)-1-(4-Fluoro-phenyl)-4a-(2-methoxy-ethoxymethyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-traza-cyclopenta[b]naphthalene.

18. A pharmaceutical composition, comprising a compound of claim 1 and a pharmaceutically acceptable excipient.

19. A method of antagonizing a glucocorticoid receptor, the method comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of claim 1 .

Assignments (3)
RELEASE OF SECURITY INTEREST IN PATENTS AT REEL/FRAME NO. 028801/0190 Recorded Aug 29, 2017
From: BIOPHARMA SECURED INVESTMENTS II SUB, S.A.R.L.
To: CORCEPT THERAPEUTICS INCORPORATED
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