Fused cyclic modulators of nuclear hormone receptor function

• US 20040077606A1
• Filed: 12/18/2002
• Published: 04/22/2004
• Est. Priority Date: 06/28/2000
• Status: Active Grant

• Current Assignee: Bristol-Myers Squibb Company, Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Harikrishnan, Lalgudi S., Salvati, Mark E., Shan, Weifang, Balog, James Aaron, Giese, Soren
• Granted Patent: US 7,001,911 B2
• Time in Patent Office: Days
• US Class Current: 514/81
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/655 Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 487/08 Bridged systems
• CPC Class Codes: C07D 487/14 Ortho-condensed systems

Abstract

Fused cyclic compounds, methods of using such compounds in the treatment of nuclear hormone receptor-associated conditions such as cancer and immune disorders, and pharmaceutical compositions containing such compounds.

Claims

1. A compound of the following formula:

2. The compound of claim 1 wherein

G is an aryl or heterocyclo group, where said group is mono- or polycyclic, and which is optionally substituted at one or more positions;

E is C═

Z₂, CHR⁷, SO₂, P═

OR², or P═

OOR²;

Z₁ is O, S, or NR⁶;

Z₂ is O, S, or NR⁶;

A₁ is CR⁷;

A₂ is CR⁷;

Y is J-J′

-J″

where J is (CR⁷R^7′

)n and n=0-2, J′

is a bond or NH, NR⁶, C═

O, cycloalkyl, or cycloalkenyl, and J″

is (CR⁷R^7′

)n and n=1-2, where Y is not a bond;

W is CR⁷R^7′

—

CR⁷R^7′

, CR⁸═

CR^8′

, CR⁷R^7′

—

C═

O, NR⁹—

CR⁷R^7′

, cycloalkyl or cycloalkenyl;

Q is H, C_1-6 alkyl, alkyl substituted with one or more halogens, C_1-6 alkyl substituted with hydroxy, alkenyl, alkynyl, Cl, F, Br, I, arylalkyl or substituted arylalkyl, CN, R¹OC═

O, R⁴C═

O, R⁵R⁶NC═

O, HOCR⁷R^7′

, R¹OCH₂, R¹O, NH₂, or NR⁴R⁵;

M is a bond or NR¹⁰, and M′

is a bond or NR¹⁰, with the proviso that at least one of M or M′

must be a bond;

L is a bond, (CR⁷R^7′

)n, NH, or NR⁵ where n=0-1;

R¹ and R^1′

are each independently H, alkyl, perfluoroalkyl, cycloalkyl, heterocyclo, cycloalkylalkyl, or heterocycloalkyl;

R² is alkyl, perfluoroalkyl, cycloalkyl, heterocyclo, cycloalkylalkyl, or heterocycloalkyl;

R³ and R^3′

are each independently H, alkyl, perfluoroalkyl, cycloalkyl, heterocyclo, cycloalkylalkyl, heterocycloalkyl, Cl, F, Br, I, CN, alkoxy, amino, NR¹R², thiol, or alkylthio;

R⁴ is H, alkyl, cycloalkyl, heterocyclo, cycloalkylalkyl, heterocycloalkyl, R¹C═

O, R¹NHC═

O, SO₂OR¹, or SO₂NR¹R^1′

;

R⁵ is alkyl, cycloalkyl, heterocyclo, cycloalkylalkyl, heterocycloalkyl, R¹C═

O, R¹NHC═

O, SO₂OR¹, or SO₂NR¹R^1′

;

R⁶ is alkyl or substituted alkyl, cycloalkyl or substituted cycloalkyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, CN, OH, OR¹, R¹C═

O, R¹NHC═

O, SO₂OR¹, or SO₂NR¹R^1′

;

R⁷ and R^7′

are each independently H, alkyl, perfluoroalkyl, cycloalkyl, heterocyclo, cycloalkylalkyl, heterocycloalkyl, aryl, arylalkyl, Cl, F, Br, I, CN, OR¹, nitro, hydroxylamine, hydroxylamide, amino, NHR⁴, NR²R⁵, NOR¹, thiol, alkylthio, R¹C═

O, R¹NHC═

O, SO₂OR¹, or SO₂NR¹R^1′

;

R⁸ and R^8′

are each independently H, alkyl or substituted alkyl, cycloalkyl or substituted cycloalkyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, OR¹, amino, NHR⁴, NR²R⁵, NOR¹, alkylthio or substituted alkylthio, R¹C═

O, R¹NHC═

O, SO₂OR¹, or SO₂NR¹R^1′

;

R⁹ and R^9′

are each independently H, alkyl, alkenyl, cycloalkyl, heterocyclo, cycloalkylalkyl, heterocycloalkyl, aryl, arylalkyl, CN, OH, OR¹, R¹C═

O, R¹OC═

O, R¹NHC═

O, SO₂R¹, SO₂OR¹, or SO₂NR¹R^1′

; and

R¹⁰ is H, alkyl, cycloalkyl, heterocyclo, cycloalkylalkyl, heterocycloalkyl, aryl, arylalkyl, CN, OH, OR¹, R¹C═

O, R¹OC═

O, R¹R^1′

NC═

O, SO₂OR¹, or SO₂NR¹R^1′

.

3. The compound of claim 1, wherein

G is an aryl or heteroaryl group, where said group is mono- or polycyclic, and which is optionally substituted at one or more positions with hydrogen, C_1-3 alkyl, allyl or substituted allyl, alkynyl, Cl, F, Br, I, CN, R¹C═

O, R¹HNC═

O, R¹R²NC═

O, haloalkyl, C_1-3 hydroxyalkyl, HOCR³R³, nitro, R¹OCH₂, R¹O, NR⁴R⁵, or SR¹;

E is C═

Z₂, CHR⁷ or SO₂;

Z₁ is O, S, or NCN;

Z₂ is O, S, or NCN;

A₁ is CR⁷;

A₂ is CR⁷;

Y is J, cyclopropyl, or cyclobutyl, where J═

(CR⁷R^7′

)n and n=1-3;

W is CR⁷R^7′

—

CR⁷R^7′

, CR⁸═

CR^8′

, CR⁷R^7′

—

C═

O, cyclopropyl, or cyclobutyl;

Q is hydrogen, C₁-C₄ alkyl, alkynyl, Cl, F, Br, I, CN, R¹OC═

O, R⁴C═

O, R⁵R⁶NC═

O, haloalkyl, C₁-C₆ hydroxyalkyl, HOCR⁷R^7′

, R¹OCH₂, R¹O, NH₂ or NR⁴R⁵;

M is a bond and M′

is a bond;

L is a bond, (CR⁷R^7′

)n, NH, or NR⁵, where n=0-1;

R¹ and R^1′

are each independently H, alkyl, cycloalkyl, heterocycloalkyl, or perfluoroalkyl;

R² is alkyl, cycloalkyl, heterocycloalkyl, or perfluoroalkyl;

R³ and R^3′

are each independently H, alkyl, perfluoroalkyl, Cl, F, Br, I, CN, alkoxy, amino, NR¹R², thiol, or alkylthio;

R⁴ is H, alkyl, cycloalkyl, heterocycloalkyl, R¹C═

O, R¹NHC═

O, SO₂OR¹, or SO₂NR¹R^1′

;

R⁵ is alkyl, cycloalkyl, heterocycloalkyl, R¹C═

O, R¹NHC═

O, SO₂OR¹, or SO₂NR¹R^1′

;

R⁷ and R^7′

are each independently H, alkyl, arylalkyl, heteroaryl, perfluoroalkyl, heteroarylalkyl, Cl, F, Br, I, CN, OR¹, amino, NHR⁴, NR²R⁵, NOR¹, thiol, alkylthio, R¹C═

O, R¹NHC═

O, SO₂OR¹, or SO₂NR¹R^1′

; and

R¹⁰ is H, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, arylalkyl, CN, R¹C═

O, R¹R^1′

NC═

O, SO₂OR¹, or SO₂NR¹R^1′

.

4. The compound of claim 1, wherein

G is an aryl or heteroaryl group, where said group is mono- or polycyclic, and which is optionally substituted at one or more positions with hydrogen, C₁-C₃ alkyl, allyl or substituted allyl, alkynyl, Cl, F, Br, I, CN, R¹C═

O, R¹HNC═

O, haloalkyl, C₁-C₃ hydroxyalkyl, HOCR³R^3′

, nitro, R¹OCH₂, R¹O, NR⁴R⁵, or SR¹;

E is C═

Z₂;

Z₁ is O;

Z₂ is O or NCN;

A₁ is CR⁷;

A₂ is CR⁷;

Y is J, where J═

(CR⁷R^7′

)n and n=1-3;

W is CR⁷R^7′

—

CR⁷R^7′

, CR⁸═

CR^8′

, or CR⁷R^7′

—

C═

O;

Q is hydrogen, C₁-C₄ alkyl, alkynyl, Cl, F, Br, I, CN, R⁴C═

O, R⁵R⁶NC═

O, haloalkyl, C₁-C₆ hydroxyalkyl, HOCR⁷R^7′

, R¹OCH₂, R¹O, NH₂ or NR⁴R⁵;

M is a bond and M′

is a bond;

L is a bond;

R¹ and R^1′

are each independently H, alkyl, or perfluoroalkyl;

R² is alkyl, or perfluoroalkyl;

R³ and R^3′

are each independently H, alkyl, perfluoroalkyl, Cl, F, Br, I, CN, alkoxy, amino, NR¹R², thiol, or alkylthio;

R⁴ is H, alkyl, R¹C═

O, R¹NHC═

O, or SO₂NR¹R^1′

;

R⁵ is alkyl, R¹C═

O, R¹NHC═

O, or SO₂NR¹R^1′

;

R⁷ and R^7′

are each independently H, alkyl, arylalkyl, heteroaryl, perfluoroalkyl, heteroarylalkyl, Cl, F, Br, I, CN, OR¹, amino, NHR⁴, NR²R⁵, NOR¹, ¹C═

O, R¹NHC═

O, or SO₂NR¹R^1′

; and

R¹⁰ is H, alkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, CN, R¹C═

O, R¹R^1′

NC═

O, or SO₂NR¹R^1′

.

5. The compound of claim 1, wherein

G is an aryl or heterocyclo group, where said group is mono- or polycyclic, and which is optionally substituted at one or more positions with substituents selected from one or more of hydrogen, alkyl or substituted alkyl, halo, heterocyclo, CN, nitro, or R¹O;

E is C═

Z₂ or CHR⁷ where R⁷ is hydrogen;

Z₁ is O or S;

Z₂ is O, S, or NR⁶ where R⁶ is CN or phenyl;

A₁ is CR⁷ where R⁷ is hydrogen;

A₂ is CR⁷ where R⁷ is hydrogen;

Y is (CR⁷R^7′

)n and n=1-2 where R⁷ and R^7′

are hydrogen;

W is CR⁷R^7′

—

CR⁷R^7′

, CR⁸═

CR^8′

, or NR⁹—

CR⁷R^7′

where R⁷,R^7′

,R⁸ and R^8′

are hydrogen;

Q is H, alkyl, alkenyl, arylalkyl or substituted arylalkyl;

M is a bond or NH and M′

is a bond;

L is a bond;

R¹ and R^1′

are each independently alkyl or substituted alkyl, heterocyclo or substituted heterocyclo, aryl or substituted aryl, arylalkyl or substituted arylalkyl; and

R⁹ is H, alkyl, alkenyl, arylalkyl, R¹C═

O, R¹OC═

O, R¹NHC═

O, or SO₂R¹.

6. A compound of claim 1 selected from the group consisting of:

(5α

8α

,8 aα

)-8,8a-Dihydro-2-[3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aα

)-2,3,8,8a-Tetrahydro-2-[3-(trifluoromethyl)phenyl]-3-thioxo-5,8-methanoimidazo[1,5-a]pyridin-1(5H)-one;

(5α

,8α

,8 aα

)-8,8a-Dihydro-8a-methyl-2-[3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aα

)-2,3,8,8a-Tetrahydro-8a-methyl-3-thioxo-2-[3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridin-1(5H)-one;

(5α

,8α

,8 aα

)-2,3,8,8a-Tetrahydro-2-(1-naphthalenyl)-3-thioxo-5,8-methanoimidazo[1,5-a]pyridin-1(5H)-one;

(5α

,8α

,8aα

)-Hexahydro-2-[3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1(5H)-one;

(5α

,8α

,8aα

)-2-[3,5-Bis(trifluoromethyl)phenyl]-8,8a-dihydro-5,8-methanoimidazo[1,5-a]pyridin-1,3(2H,5H)-one;

(5α

,8α

,8aα

)-8,8a-Dihydro-2-(2-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aα

)-8,8a-Dihydro-2-(1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aα

)-2-(3,5-Dichlorophenyl)-8,8a-dihydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8 aβ

)]-Tetrahydro-2-[3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5R-(5α

,8α

,8α

β

)]-Tetrahydro-2-[3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

Tetrahydro-2-(1-naphthalenyl)-5,8-ethanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

Tetrahydro-2-[3-(trifluoromethyl)phenyl]-5,8-ethanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aα

)-2-(4-Bromo-1-naphthalenyl)-8,8a-dihydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8 aβ

)]-2-(3,5-Dichlorophenyl)tetrahydro-5,8-methanoirmidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8 aβ

)]-2-(4-Bromo-1-naphthalenyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5R-(5α

,8α

,8 aβ

)]-2-(4-Bromo-1-naphthalenyl)tetrahydro-5,8-methanoirmidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5R-(5α

,8α

,8 aβ

)]-2-(3,5-Dichlorophenyl)tetrahydro-5,8-methanoirmidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aβ

)-Tetrahydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aβ

)-Hexahydro-2-(1-naphthaleny)-3-thioxo-5,8-methanoirmidazo[1,5-a]pyridine-1(5H)-one;

(5α

,8α

,8aβ

)-Hexahydro-3-thioxo-2-[3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1(5H)-one;

(5α

,8α

,8aα

)-2-(3,5-Dichlorophenyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aβ

)-Tetrahydro-2-[3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aα

)-Tetrahydro-2-[3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aα

)-Tetrahydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aα

)-Hexahydro-3-thioxo-2-[3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1(5H)-one;

[5S-(5α

,8α

,8 aα

)]-Tetrahydro-2-[3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aβ

)-Tetrahydro-2-(2-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aα

)-Tetrahydro-2-(2-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aα

)-Tetrahydro-8a-methyl-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aα

)-8,8a-Dihydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aβ

)-8,8a-Dihydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aα

)-Tetrahydro-8a-(2-propenyl)-2-[3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aα

)-Tetrahydro-8a-(phenylmethyl)-2-[3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[(Octahydro-1-oxo-2-phenyl-5,8-methanoimidazo[1,5-a]pyridin-3-ylidene)amino]carbonitrile;

(5α

,8α

,8 aβ

)-[[2-(3-Chloro-4-fluorophenyl)octahydro-1-oxo-5,8-methanoimidazo[1,5-a]pyridin-3-ylidene]amino]carbonitrile;

(5α

,8α

,8 aα

)-[[2-(3-Chloro-4-fluorophenyl)octahydro-1-oxo-5,8-methanoimidazo[1,5-a]pyridin-3-ylidene]amino]carbonitrile;

(5α

,8α

,8 aβ

)-2-(3-Chlorophenyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aα

)-2-(3-Chlorophenyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aβ

)-[[2-(3-Chlorophenyl)octahydro-1-oxo-5,8-methanoimidazo[1,5-a]pyridin-3-ylidene]amino]carbonitrile;

(5α

,8α

,8 aα

)-[[2-(3-Chlorophenyl)octahydro-1-oxo-5,8-methanoimidazo[1,5-a]pyridin-3-ylidene]amino]carbonitrile;

(5α

,8α

,8α

β

)-[[2-(3,5-Dichlorophenyl)octahydro-1-oxo-5,8-methanoimidazo[1,5-a]pyridin-3-ylidene]amino]carbonitrile;

(5α

,8α

,8 aα

)-[[2-(3,5-Dichlorophenyl)octahydro-1-oxo-5,8-methanoimidazo[1,5-a]pyridin-3-ylidene]amino]carbonitrile;

(5α

,8α

,8 aα

)-2-(3-Chloro-4-fluorophenyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aβ

)-2-(3-Chloro-4-fluorophenyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aβ

)-[[2-(3,4-Dichlorophenyl)octahydro-1-oxo-5,8-methanoimidazo[1,5-a]pyridin-3-ylidene]amino]carbonitrile;

(5α

,8α

,8 aα

)-[[2-(3,4-Dichloro-phenyl)octahydro-1-oxo-5,8-methanoimidazo[1,5-a]pyridin-3-ylidene]amino]-carbonitrile;

(5α

,8α

,8 aβ

)-Tetrahydro-2-[4-nitro-3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aα

)-Tetrahydro-2-[4-nitro-3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aβ

)-2-(3-Chloro-4-fluorophenyl)-8,8a-dihydro-5,8-methano-imidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aα

)-2-(3-Chloro-4-fluorophenyl)-8,8a-dihydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aα

)-8,8a-Dihydro-8a-methyl-2-[4-nitro-3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8 aβ

)-4-(Octahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyridin-2-yl)-2-(trifluoromethyl)benzonitrile;

(5α

,8α

,8 aα

)-4-(Octahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyridin-2-yl)-2-(trifluoromethyl)benzonitrile;

(5α

,8α

,8 aα

)-4-(1,2,3,5,8,8a-Hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyridin-2-yl)-2-(trifluoromethyl)benzonitrile;

(5α

,8α

,8 aα

)-Hexahydro-2-(2-naphthaleny)-3-(phenylimino)-5,8-methanoimidazo[1,5-a]pyridine-1(5H)-one;

(5α

,8α

,8 aβ

)-2-Methoxy-4-(octahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyridin-2-yl)-1-naphthalenecarbonitrile;

(5α

,8α

,8 aα

)-2-Methoxy-4-(octahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyridin-2-yl)-1-naphthalenecarbonitrile;

(5α

,8α

,8 aα

)-8a-[(4-Bromophenyl)methyl]-2-(3,5-dichlorophenyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8 aβ

)]-Tetrahydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8 aα

)]-Tetrahydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5R-(5α

,8α

,8 aα

)]-Tetrahydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5R-(5α

,8α

,8 aα

)]-4-(Octahydro-1,3-dioxo-5,8-methano-imidazo[1,5-a]pyridin-2-yl)-2-(trifluoromethyl)benzonitrile;

[5S-(5α

,8α

,8 aβ

)]-Tetrahydro-2-[4-nitro-3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8 aα

)]-Tetrahydro-2-[4-nitro-3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8 aβ

)]-4-(Octahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyridin-2-yl)-2-(trifluoromethyl)benzonitrile;

[5S-(5α

,8α

,8 aα

)]-4-(Octahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyridin-2-yl)-2-(trifluoromethyl)benzonitrile;

(5α

,8α

,8aα

)-2-(Benzo[b]thiophen-3-yl)-8,8a-dihydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5R-(5α

,8α

,8 aβ

)]-4-(Octahydro-1,3-dioxo-5,8-methano-imidazo[1,5-a]pyridin-2-yl)-2-(trifluoromethyl)benzonitrile;

[5R-(5α

,8α

,aα

)]-Tetrahydro-2-[4-nitro-3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5R-(5α

,8α

,8 aβ

)]-Tetrahydro-2-[4-nitro-3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5R-(5α

,8α

,8 aβ

)]-Tetrahydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(6α

,9α

,9aα

)-Tetrahydro-2-[3-(trifluoromethyl)-phenyl]-6,9-methano-2H-pyrido[1,2-d][1,2,4]triazine-1,4(3H,9aH)-dione;

(5α

,8α

,8aα

)-8,8a-Dihydro-2-(1H-indol-3-yl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aα

)-2-(3-Chlorophenyl)-8,8a-dihydro-5,8-methano-imidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aβ

)-8,8a-Dihydro-2-(1H-indol-3-yl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aα

)-2-(Benzo[b]thiophene-3-yl)-8,8a-dihydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aα

) &

(5α

,8α

,8aβ

)-2-(1,2-Benzisoxazol-3-yl)tetrahydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aα

)-4-(Octahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyridin-2-yl)-1-naphthalenecarbonitrile;

(5α

,8α

,8aβ

)-4-(Octahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyridin-2-yl)-1-naphthalenecarbonitrile;

(5α

,8α

,8aβ

)-Tetrahydro-2-(1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aα

)-Tetrahydro-2-(1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aα

)-2-(4-Fluoro-1-naphthalenyl)tetrahydro-5,8-methanoirnidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aβ

)-2-(4-Fluoro-1-naphthalenyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aβ

)-2-(4-Chloro-1-naphthalenyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aα

)-2-(4-Chloro-1-naphthalenyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aα

)-8,8a-Dihydro-2-(1-oxidobenzo[b]thiophen-3-yl)-5,8-methanoimidazo-[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aα

)-4-(1,2,3,5,8,8a-Hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyridin-2-yl)-1-naphthalenecarbonitrile;

(5α

,8α

,8aα

)-Tetrahydro-2-[4-(1H-tetrazol-5-yl)-1-naphthalenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5S,8S,8aR)-4-[Octahydro-7-[(1,1-dimethylethoxy)-carbonyl]-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazin-2-yl]-2-(trifluoromethyl)-benzonitrile;

(5R,8R,8aR)-4-[Octahydro-7-[(1,1-dimethylethoxy)carbonyl]-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazin-2-yl]-2-(trifluoromethyl)benzonitrile;

(5S-(5α

,8α

,8aα

)]-4-(Hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazin-2(3H)-yl)-2-(trifluoromethyl)benzonitrile;

(5R,8R,8aR)-4-[Octahydro-7-[(1,1-dimethylethoxy)-carbonyl]-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazin-2-yl]-2-(trifluoromethyl)-benzonitrile;

(5S,8S,8aR)-4-[Octahydro-7-[(1,1-dimethylethoxy)carbonyl]-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazin-2-yl]-2-(trifluoromethyl)benzonitrile;

[5S-(5α

,8α

,8aα

)]Hexahydro-2-(4-nitro-1-naphthalenyl)-1,3-dioxo-5,8-methano-imidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 1,1-dimethylethyl ester;

[5S-(5α

,8α

,8aα

)]-Tetrahydro-2-(4-nitro-1-naphthalenyl)-5,8 methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-7-[(4-Fluorophenyl)sulfonyl]-tetrahydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

(5α

,8α

,8aα

)-2-(7-Fluoro-3-benzofuranyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aβ

)-2-(7-Fluoro-3-benzofuranyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-2-[4-Cyano-3-(trifluoromethyl)phenyl]hexahydro-8a-methyl-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 1,1 -dimethylethyl ester;

[5S-(5α

,8α

,8aα

)]-4-(Hexahydro-1,4-dioxo-8a-methyl-5,8-methanoimidazo [1,5-a]pyrazin-2(3H)-yl)-2-(trifluoromethyl)benzonitrile;

[5S-(5α

,8α

8aα

)]-4-(7-Benzoylhexahydro-8a-methyl-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazin-2(3H)-yl)-2-(trifluoromethyl)benzonitrile;

[5S-(5α

,8α

,8aα

)]-7-(4-Fluorobenzoyl)tetrahydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-1-naphthalenyl)tetrahydro-7-(5-isoxazolylcarbonyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione (102A), [5S-(5α

,8α

,8aα

)]-2-(4-Cyano-1-naphthalenyl)hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 4-fluorophenyl ester (102B), [5S-(5α

,8α

,8aα

)]-2-(4-Cyano-1-naphthalenyl)tetrahydro-7-[(1-methyl-1H-imidazol-4-yl)sulfonyl]-5,8-methano-imidazo[1,5-a]pyrazine-1,3(2H,5H)-dione (102C);

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-1-naphthalenyl)-N-(4-fluorophenyl)hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxamide;

[5S-(5α

,8α

,8a β

)]-Tetrahydro-2-(4-nitro-1-naphthalenyl)-7-(phenylmethyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5R-(5α

,8α

,8aα

)]-2-[4-Cyano-3-(trifluoromethyl)phenyl]hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 1,1-dimethylethyl ester;

[5R-(5α

,8α

,8aα

)]-Hexahydro-2-(4-nitro-1-naphthalenyl)-1,3-dioxo-5,8-methanoimnidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 1,1-dimethylethyl ester;

[5R-(5α

,8α

,8aα

)]-Tetrahydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5R-(5α

,8α

,8aα

)]-4-(Hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazin-2(3H)-yl)-2-(trifluoromethyl)benzonitrile;

[5S-(5α

,8α

,8aα

)]-4-(7-Benzoylhexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazin-2(3H)-yl)-2-(trifluoromethyl)benzonitrile;

[5S-(5α

,8α

,8aα

)]-2-[4-Cyano-3-(trifluoromethyl)phenyl]hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, phenylmethyl ester;

[5S-(5α

,8α

,8aα

)]-Tetrahydro-2-(2-methyl-4-nitrophenyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-4-(Hexahydro-7-methyl-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazin-2(3H)-yl)-2-(trifluoromethyl)benzonitrile;

[5S-(5α

,8α

,8aα

)]-7-Benzoyltetrahydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-Hexahydro-2-(4-nitro-1-naphthalenyl)-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, phenylmethyl ester;

[5S-(5α

,8α

,8aα

)]-Tetrahydro-2-(3-methyl-4-nitrophenyl)-5,8-methano-imidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-Tetrahydro-7-methyl-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-Tetrahydro-2-(4-nitro-1-naphthalenyl)-7-(2-propenyl)-5,8-methano-imidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-4-[Hexahydro-1,3-dioxo-7-(phenylmethyl)-5,8-methanoimidazo[1,5-a]pyrazin-2(3H)-yl]-2-(trifluoromethyl)benzonitrile;

[5R-(5α

,8α

,8aα

)]-Tetrahydro-2-(4-nitro-1-naphthalenyl)-7-(2-propenyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5R-(5α

,8α

,8aα

)]-7-[(4-Fluorophenyl)sulfonyl]tetrahydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5R-(5α

,8α

,8aα

)]-7-Benzoyltetrahydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-Tetrahydro-2-(4-nitro-1-naphthalenyl)-7-[(phenylmethyl)sulfonyl]-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-Tetrahydro-2-(4-nitro-1-naphthalenyl)-7-(phenylacetyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-Tetrahydro-2-(4-nitro-1-naphthalenyl)-7-(3phenyl-1-oxopropyl)-5,8-methanoimidazol[1,5-a]pyrazine-1,3(2H,5H)-dione;

(5α

,8α

,8aα

)-2-(2-Benzofuranyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aα

)-Tetrahydro-2-[3-methoxy-4-(4-oxazolyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-1-naphthalenyl)hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 1,1-dimethylethyl ester;

[5S-(5α

,8α

,8aα

)]-4-(Hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazin-2(3H)-yl)-1-naphthalenecarbonitrile;

[5S-(5α

,8α

,8aα

)]-4-[Hexahydro-7-(2-methyl-1-oxopropyl)-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazin-2(3H)-yl]-1-naphthalenecarbonitrile;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-3-iodophenyl)hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 1,1-dimethylethyl ester;

[5S-(5α

,8α

,8aα

)]-4-(Hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazin-2(3H)-yl)-2-iodobenzonitrile;

(5α

,8α

,8aα

)-Tetrahydro-2-(2-methyl-3-benzofuranyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aα

)-2-(2,2-Dimethyl-2H-1-benzopyran-4-yl)tetrahydro-5,8-methanoimidazo[1,5-a]pyridne-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-7-Acetyltetrahydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-Tetrahydro-7-(2-methyl-1-oxopropyl)-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-7-[4-Fluoro-3-(trifluoromethyl)-benzoyl]tetrahydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-7-(4-Chloro-3-nitrobenzoyl)tetrahydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-Tetrahydro-7-(5-isoxazolylcarbonyl)-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-7-(4-Butylbenzoyl)tetrahydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-N-(3-Chloro-4-fluorophenyl)-hexahydro-2-(4-nitro-1-naphthalenyl)-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxamide;

[5S-(5α

,8α

,8aα

)]-Tetrahydro-2-(4-nitro-1-naphthalenyl)-7-[4-(trifluoromethyl)benzoyl]-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-Hexahydro-N-(1-methylethyl)-2-(4-nitro-1-naphthalenyl)-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxamide;

[5S-(5α

,8α

,8aα

)]-N-(4-Fluorophenyl)hexahydro-2-(4-nitro-1-naphthalenyl)-1,3-dioxo-5,8-methanocmidazo[1,5-a]pyrazine-7(8H)-carboxamide;

[5S-(5α

,8α

,8aα

)]-N-[(4-Fluorophenyl)methyl]hexahydro-2-(4-nitro-1-naphthalenyl)-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxamide;

[5S-(5α

,8α

,8aα

)]-Hexahydro-2-(4-nitro-1-naphthalenyl)-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 4-nitrophenyl ester;

[5S-(5α

,8α

,8aα

)]-Hexahydro-2-(4-nitro-1-naphthalenyl)-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 4-fluorophenyl ester;

[5S-(5α

,8α

,8aα

)]-Hexahydro-2-(4-nitro-1-naphthalenyl)-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 4-(nitrophenyl)-methyl ester;

[5S-(5α

,8α

,8aα

)]-Hexahydro-2-(4-nitro-1-naphthalenyl)-1,3-dioxo-5,8-methanoirmidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, butyl ester;

[5S-(5α

,8α

,8aα

)]-Tetrahydro-7-[(1-methyl-1H-imidazol-4-yl)sulfonyl]-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-7-[(4-Chloro-3-nitrophenyl)sulfonyl]tetrahydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-Tetrahydro-2-(4-nitro-1-naphthalenyl)-7-[(2,2,2-trifluoroethyl)sulfonyl]-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-7-Acetyl-2-(4-cyano-1-naphthalenyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-1-naphthalenyl)tetrahydro-7-(2-methyl-1-oxopropyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-1-naphthalenyl)-7-[4-fluoro-3-(trifluoromethyl)benzoyl]tetrahydro-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-7-(4-Chloro-3-nitrobenzoyl)-2-(4-cyano-1-naphthalenyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-7-(4-Butylbenzoyl)-2-(4-cyano-1-naphthalenyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-N-(3-Chloro-4-fluorophenyl)-2-(4-cyano-1-naphthalenyl)hexahydro-1,3-dioxo-5,8-methanoimidazo-[1,5-a]pyrazine-7(8H)-carboxamide;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-1-naphthalenyl)-hexahydro-1,3-dioxo-N-[4-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxamide;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-1-naphthalenyl)-hexahydro-N-(1-methylethyl)-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxamide;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-1-naphthalenyl)-N-[(4-fluorophenyl)methyl]hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxamide;

[5S-(5-(5α

,8α

,8aα

)]-2-(4-Cyano-1-naphthalenyl)hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 4-(nitrophenyl)-methyl ester;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-1-naphthalenyl)hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, butyl ester;

[5S-(5α

,8α

,8aα

)]-7-[(4-Chloro-3-nitrophenyl)sulfonyl]-2-(4-cyano-1-naphthalenyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-1-naphthalenyl)tetrahydro-7-[(2,2,2-trifluoroethyl)sulfonyl]-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-7-Acetyl-2-[4-cyano-3-(trifluoromethyl)phenyl]tetrahydro-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-2-[4-Cyano-3-(trifluoromethyl)phenyl]tetrahydro-7-(2-methyl-1-oxopropyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-2-[4-Cyano-3-(trifluoromethyl)phenyl]-7-[4-fluoro-3-(trifluoromethyl)benzoyl]tetrahydro-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-7-(4-Chloro-3-nitrobenzoyl)-2-[4-cyano-]3-(trifluoromethyl)phenylltetrahydro-5,8-methanoimidazo[1,5-a] pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-2-[4-Cyano-3-(trifluoromethyl)phenyl]tetrahydro-7-(5-isoxazolylcarbonyl)-5,8-methano-imidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-7-(4-Butylbenzoyl)-2-[4-cyano-3-(trifluoromethyl)phenyl]tetrahydro-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-N-(3-Chloro-4-fluorophenyl)-2-[4-cyano-3-(trifluoromethyl)phenyl]hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxamide;

[5S-(5α

,8α

,8aα

)]-2-[4-Cyano-3-(trifluoromethyl)phenyl]-hexahydro-1,3-dioxo-N-[4-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxamide;

[5S-(5α

,8α

,8aα

)]-2-[4-Cyano-3-(trifluoromethyl)-phenyl]hexahydro-N-(1-methylethyl)-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxamide;

[5S-(5α

,8α

,8aα

)]-2-[4-Cyano-3-(trifluoromethyl)phenyl]-N-(4-fluorophenyl)hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxamide;

[5S-(5α

,8α

,8aα

)]-2-[4-Cyano-3-(trifluoromethyl)phenyl]-N-[(4-fluorophenyl)methyl]hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxamide;

[5S-(5α

,8α

,8aα

)]-2-[4-Cyano-3-(trifluoromethyl)phenyl]-hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 4-nitrophenyl ester;

[5S-(5α

,8α

,8aα

)]-2-[4-Cyano-3-(trifluoromethyl)phenyl]-hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 4-fluorophenyl ester;

[5S-(5α

,8α

,8aα

)]-2-[4-Cyano-3-(trifluoromethyl)phenyl]-hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 4-(nitrophenyl)methyl ester;

[5S-(5α

,8α

,8aα

)]-2-[4-Cyano-3-(trifluoromethyl)-phenyl]hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, butyl ester;

[5S-(5α

,8α

,8aα

)]-2-[4-Cyano-3-(trifluoromethyl)phenyl]tetrahydro-7-[(1-methyl-1H-imidazol-4-yl)sulfonyl]-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-7-[(4-Chloro-3-nitrophenyl)sulfonyl]-2-[4-cyano-3-(trifluoromethyl)phenyl]tetrahydro-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-2-[4-Cyano-3-(trifluoromethyl)-phenyl]tetrahydro-7-[(2,2,2-trifluoroethyl)sulfonyl]-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-7-Acetyl-2-(4-cyano-3-iodophenyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-3-iodophenyl)tetrahydro-7-(2-methyl-1-oxopropyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-3-iodophenyl)-7-[4-fluoro-3-(trifluoromethyl)benzoyl]tetrahydro-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-7-(4-Chloro-3-nitrobenzoyl)-2-(4-cyano-3-iodophenyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-3-iodophenyl)tetrahydro-7-(5-isoxazolylcarbonyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-7-(4-Butylbenzoyl)-2-(4-cyano-3-iodophenyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-N-(3-Chloro-4-fluorophenyl)-2-(4-cyano-3-iodophenyl)hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxamide;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-3-iodophenyl)hexahydro-1,3-dioxo-N-[4-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxamide;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-3-iodophenyl)hexahydro-N-(1-methylethyl)-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxamide;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-3-iodophenyl)-N-(4-fluorophenyl)hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxamide;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-3-iodophenyl)-N-[(4-fluorophenyl)-methyl]hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxamide;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-3-iodophenyl)hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 4-nitrophenyl ester;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-3-iodophenyl)hexahydro-1,3-dioxo-5,8-methano-imidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 4-fluorophenyl ester;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-3-iodophenyl)hexahydro-1,3-dioxo-5,8-methano-imidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, (4-nitrophenyl)methyl ester;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-3-iodophenyl)hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, butyl ester;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-3-iodophenyl)tetrahydro-7-[(1-methyl-1H-imidazol-4-yl)sulfonyl]-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-7-[(4-Chloro-3-nitrophenyl)sulfonyl]-2-(4-cyano-3-iodophenyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-2-(4-Cyano-3-iodophenyl)tetrahydro-7-(methylsulfonyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aα

)]-4-(Hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazin-2(3H)-yl)-2-(trifluoromethyl)benzonitrile;

[5R-(5α

,8α

,8aβ

)]-Hexahydro-2-(4-nitro-1-naphthalenyl)-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 1,1-dimethylethyl ester;

[5S-(5α

,8α

,8aα

)]-2-[4-Cyano-3-(trifluoromethyl)phenyl]-hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 1,1-dimethylethyl ester;

[5S-(5α

,8α

,8aβ

)]-Tetrahydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione, trifluoroacetate;

[5R-(5α

,8α

,8aβ

)]-2-[4-Cyano-3-(trifluoromethyl)phenyl]hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 1,1-dimethylethyl ester;

[5S-(5α

,8α

,8aβ

)]-Hexahydro-2-(4-nitro-1-naphthalenyl)-1,3-dioxo-5,8-methano-imidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 1,1-dimethylethyl ester;

[5R-(5α

,8α

,8aβ

)]-4-(Hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazin-2(1H)-yl)-2-(trifluoromethyl)benzonitrile;

[5S-(5α

,8α

,8aβ

)]-4-(7-Benzoylhexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazin-2(3H)-yl)-2-(trifluoromethyl)benzonitrile;

(5α

,8α

,8aβ

)-Tetrahydro-2-(2-methyl-4-nitrophenyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aβ

)]-7-Benzoyltetrahydro-2-(4-nitro-1-naphthalenyl)-5,8-methanoimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione;

(5α

,8α

,8aβ

)-2-(2-Benzofuranyl)tetrahydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aβ

)-Tetrahydro-2-(4,5,6,7-tetrafluoro-2-methyl-3-benzofuranyl)-5,8-methanoinidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

(5α

,8α

,8aβ

)-Tetrahydro-2-[3-methoxy-4-(4-oxazolyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aβ

)]-2-(4-Cyano-1-naphthalenyl)hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 1,1-dimethylethyl ester;

[5S-(5α

,8α

,8aβ

)]-2-(4-Cyano-3-iodophenyl)hexahydro-1,3-dioxo-5,8-methano-imidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 1,1-dimethylethyl ester;

(5α

,8α

,8aβ

)-Tetrahydro-2-(2-methyl-3-benzofuranyl)-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

[5S-(5α

,8α

,8aβ

)]-2-(3,5-Dichlorophenyl)hexahydro-1,3-dioxo-5,8-methanoimidazo[1,5-a]pyrazine-7(8H)-carboxylic acid, 1,1-dimethylethyl ester; and

(5α

,8α

,8aβ

)-2-(2,2-Dimethyl-2H-1-benzopyran-4-yl)tetrahydro-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione;

or a pharmaceutically acceptable salt, solvate, prodrug or stereoisomer thereof.

7. A pharmaceutical composition comprising the following formula:

8. A pharmaceutical composition of claim 7 further comprising another anti-cancer agent.

9. A method of modulating the function of a nuclear hormone receptor which comprises administering to a mammalian species in need thereof an effective nuclear hormone receptor modulating amount of a compound of the following formula I:

10. The method of claim 9 wherein said nuclear hormone receptor is a steroid binding nuclear hormone receptor.

11. The method of claim 9 wherein said nuclear hormone receptor is the androgen receptor.

12. The method of claim 9 wherein said nuclear hormone receptor is the estrogen receptor.

13. The method of claim 9 wherein said nuclear hormone receptor is the progesterone receptor.

14. The method of claim 9 wherein said nuclear hormone receptor is the glucocorticoid receptor.

15. The method of claim 9 wherein said nuclear hormone receptor is the mineralocorticoid receptor.

16. The method of claim 9 wherein said nuclear hormone receptor is the aldosterone receptor.

17. The method of claim 9 wherein said nuclear hormone receptor is the RORbeta receptor.

18. The method of claim 9 wherein said nuclear hormone receptor is the COUP-TF2 receptor.

19. A method for treating a condition or disorder comprising administering to a mammalian species in need thereof a therapeutically effective amount of a compound of the following formula:

20. A method for the preparation of a compound of the following formula IIa:

21. A compound of the following formula E:

22. A compound of the following formula F:

23. A compound of the following formula G:

24. A compound of the following formula H:

25. A compound of the following formula J:

26. A compound of the following formula IIa