Aryl and arylalkyl substituted pyrazolyl and pyrimidinyl tricyclic enones as antioxidant inflammation modulators
The present application relates to: (a) compounds of Formula (I): and salts thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , m, n, X and Y are as defined in the specification; (b) compositions comprising such compounds and salts; and (c) methods of use of such compounds, salts, and compositions, particularly use for the treatment and prevention of diseases such as those associated with oxidative stress and inflammation.
1. A compound of Formula (I),
or a pharmaceutically acceptable salt thereof, wherein
is a single or double bond;
m is 0 or 1;
n is 1 or 2;
p is 1, 2, or 3;
q is 1, 2, or 3;
r is 1, 2, 3, or 4;
X is NC—, F 3 C—, R 1x C(O)—, or O 2 N—;
Y is G 1 -, G 1 -(CR a R b )—, G 2 -, or G 2 -(CR a R b )—;
R 1 and R 2 are each independently hydrogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, amido, amino, halogen, hydroxy, G R1a -, G R1a -(CR a R b ) p —, G R1b -, R 1a C(O)—, (R 1a ) 2 N—, G R1a NH—, G R1a -(CR a R b ) p —NH—, G R1a O—, and R 1a CO 2 —; or
R 1 and R 2 joined together with the carbon atom to which they are attached form a C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkenyl, or 4-6-membered heterocycle optionally substituted with C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, cyano, halogen, hydroxy, Or oxo;
R 3 is absent, hydrogen, C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 1 -C 6 -fluoroalkyl, G 3a - or G 3a -(CR a R b ) q —; provided that R 3 is absent when and only when the atom to which it is attached forms part of a double bond;
R 4 is hydrogen, C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 1 -C 6 -fluoroalkyl, amino, C 1 -C 6 -alkylamino, C 1 -C 6 -dialkylamino, C 1 -C 6 -alkoxy, cyano, halogen, hydroxy, G 4a -, G 4b -, G 4a -(CR a R b ) p —, G 4b -(CR a R b ) p —, G 4a O— or G 4a NH—;
R 5 is absent, hydrogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -fluoroalkyl, G R5a -, G R5a -(CR a R b )—, R 5a C(O)—, G R5a C(O)—, hydroxy-C 1 -C 6 -alkyl-C(O)—, R 5a O 2 C—, G R5a O 2 C—, G R5a HNC(O)—, R 5a O 2 CNHCH 2 C(O)—, H 2 NHCH 2 C(O)—, R 5a SO 2 —, or G R5a SO 2 —; provided that R 5 is absent when and only when the atom to which it is attached forms part of a double bond;
R 6 is hydrogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, amino, C 1 -C 6 -alkylamino, C 1 -C 6 -dialkylamino, hydroxy, G 6a -, G 6a N(R a )—, G 6a O— or G 6b -;
R a and R b are, at each occurrence, independently hydrogen, C 1 -C 6 -alkyl, or C 1 -C 6 -haloalkyl;
R 1a is, at each occurrence, independently hydrogen, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl or C 1 -C 4 -haloalkyl;
R 1x is hydroxy, C 1 -C 6 -alkoxy, amino, C 1 -C 6 -alkylamino, C 1 -C 6 -dialkylamino, or C 1 -C 6 -alkylsulfonylamino;
R G1a is, at each occurrence, independently hydrogen, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl or C 1 -C 4 -haloalkyl;
R G1b is, at each occurrence, independently C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl or C 1 -C 4 -haloalkyl;
R G2a is, at each occurrence, independently hydrogen, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl or C 1 -C 4 -haloalkyl;
R G2b is, at each occurrence, independently C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl or C 1 -C 4 -haloalkyl;
R G4a is, at each occurrence, independently C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl or C 1 -C 4 -haloalkyl;
R 5a is, at each occurrence, independently hydrogen, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl or C 1 -C 4 -haloalkyl;
R G6a is, at each occurrence, independently C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl or C 1 -C 4 -haloalkyl;
R G6b is, at each occurrence, independently hydrogen, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl or C 1 -C 4 -haloalkyl;
R G6c is, at each occurrence, independently C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl or C 1 -C 4 -haloalkyl;
R G6d is, at each occurrence, independently hydrogen, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl or C 1 -C 4 -haloalkyl;
G 1 is phenyl optionally substituted with 1, 2, 3, 4 or 5 C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, carboxy, cyano, cyano-C 1 -C 6 -alkyl, halogen, halo-C 1 -C 6 -alkyl, hydroxy, hydroxy-C 1 -C 6 -alkyl, R G1b O 2 C—, R G1a HN(O)C—, (R G1a ) 2 N(O)C—, G 1a C(O)—, G 1b HN(O)C—, G 1b -, R G1a C(O)N(R G1a )—, R G1b (O)CN(R G1a )—, R G1b O2SN(R G1a )—, (R G1a ) 2 N—, G 1b O—, G 1b CH 2 O—, R G1a CO 2 —, (R G1a ) 2 NCO 2 —, HS—, R G1b S—, R G1b S(O)—, R G1b SO 2 — or (R G1a ) 2 NSO 2 —;
G 2 is a 5-6-membered heteroaryl optionally substituted with 1, 2, 3, 4 or 5 C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, carboxy, cyano, cyano-C 1 -C 6 -alkyl, halogen, halo-C 1 -C 6 -alkyl, hydroxy, hydroxy-C 1 -C 6 -alkyl, R G2b CO 2 —, R G2a HNC(O)—, (R G2a ) 2 NC(O)—, G 2a C(O)—, G 2b HNC(O)—, G 2b -, R G2a C(O)N(R G2a )—, R G2b OC(O)N(R G2a )—, R G2b SO 2 N(R G2a )—, (R G2a ) 2 N—, G 2b O—, G 2b CH 2 O—, R G2a CO 2 —, (R G2a ) 2 NCO 2 —, HS—, R G2b S—, R G2b S(O)—, R G2b SO 2 —, or (R G2a ) 2 NSO 2 —;
G 1a is a 4-6-membered heterocycle optionally substituted with 1, 2, 3 or 4 C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, cyano, halogen, hydroxy, or oxo;
G 1b is phenyl or 5-6-membered heteroaryl optionally substituted with 1, 2, 3, 4 or 5 C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, cyano, halogen, hydroxy, or nitro;
G R1a is phenyl or 5-6-membered heteroaryl optionally substituted with 1, 2, 3, 4 or 5 C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, cyano, halogen, hydroxy, or nitro;
G R1b is a 4-6-membered heterocycle optionally substituted with 1, 2, 3 or 4 C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, cyano, halogen, hydroxy, or oxo;
G 2a is a 4-6-membered heterocycle optionally substituted with 1, 2, 3 or 4 C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, cyano, halogen, hydroxy, or oxo;
G 2b is phenyl or 5-6-membered heteroaryl optionally substituted with 1, 2, 3, 4 or 5 C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, cyano, halogen, hydroxy, or nitro;
G 3a is phenyl or 5-6-membered heteroaryl optionally substituted with 1, 2, 3, 4 or 5 C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, cyano, halogen, or hydroxy;
G 4a is phenyl or 5-6-membered heteroaryl optionally substituted with 1, 2, 3, 4 or 5 C 1 -C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, amido, carboxy, cyano, halogen, hydroxy, R G4a O 2 C—, R G4a C(O)—, (R G4a ) 2 NC(O)—, or G 4a1 -;
G 4a1 is phenyl or 5-6-membered heteroaryl optionally substituted with 1, 2, 3, 4 or 5 C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, cyano, halogen, hydroxy, or nitro;
G 4b is a 4-6-membered heterocycle optionally substituted with 1, 2, 3 or 4 C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, cyano, halogen, hydroxy, or oxo;
G R5a is phenyl or 5-6-membered heteroaryl optionally substituted with 1, 2, 3, 4 or 5 C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, cyano, halogen, hydroxy, or nitro;
G 6a is C 6 -C 10 -aryl or 5-10-membered heteroaryl optionally substituted with 1, 2, 3, or 4 C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, amino, C 1 -C 6 -alkylsulfonylamino, carboxy, halogen, hydroxy, hydroxyC 1 -C 6 -alkyl, R G6a C(O)—, R G6a O 2 C—, HO 2 C—(CR a R b ) r —, R G6a O 2 C—(CR a R b ) r —, (R G6b ) 2 N(O)C—(CR a R b ) r —, R G6a CO 2 —(CR a R b ) r —, G 6c -, or G 6d -;
G 6b is 4-6-membered heterocycle optionally substituted with 1, 2, 3, or 4 C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkoxy, cyano, halogen, hydroxy, or oxo;
G 6c is phenyl or 5-6-membered heteroaryl optionally substituted with 1, 2, 3, or 4 C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkoxy, amino, C 1 -C 6 -alkylsulfonylamino, di(C 1 -C 6 -alkylsulfonyl)amino, C 1 -C 6 -alkylsulfonylaminoC 1 -C 6 -alkyl, carboxy, cyano, halogen, hydroxy, hydroxyC 1 -C 6 -alkyl, R G6c C(O)—, R G6c O 2 C—, (R G6d ) 2 NC(O)—, HO 2 C—(CR a R b ) r —, R G6c O 2 C—(CR a R b ) r —, (R G6d ) 2 NC(O)—(CR a R b ) r —, or R G6c CO 2 —(CR a R b ) r —; and
G 6d is 4-6-membered heterocycle optionally substituted with 1, 2, 3, or 4 C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkoxy, cyano, halogen, hydroxy, or oxo.
2. The compound of claim 1 , or salt thereof, further defined by the Formula (Ia).
3. The compound of claim 2 , or salt thereof, further defined by the Formula (Ia-1).
4. The compound of claim 3 , or salt thereof, wherein
X is NC— or R 1x C(O)—;
Y is G 1 - or G 1 -(CR a R b )—; and
R 1x is hydroxy, C 1 -C 6 -alkoxy, amino, C 1 -C 6 -alkylamino, C 1 -C 6 -dialkylamino, or C 1 -C 6 -alkylsulfonylamino.
5. The compound of claim 4 , or salt thereof, wherein
X is NC—; and
Y is G 1 -.
6. The compound of claim 5 , or salt thereof, wherein
r is 1, 2, or 3;
R 4 is hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkylamino, C 1 -C 6 -dialkylamino, C 1 -C 6 -alkoxy, halogen, G 4a -, G 4b -, or G 4a NH—;
R 6 is hydrogen, C 1 -C 6 -alkoxy, hydroxy, G 6a -, G 6a N(R a )— or G 6b -;
R a and R b are, at each occurrence, hydrogen;
R G1a is, at each occurrence, independently hydrogen or C 1 -C 4 -alkyl;
R G1b is, at each occurrence, C 1 -C 4 -alkyl;
R G4a is, at each occurrence, C 1 -C 4 -alkyl;
R G6a is, at each occurrence, C 1 -C 4 -alkyl;
R G6b is, at each occurrence, hydrogen;
R G6c is, at each occurrence, C 1 -C 4 -alkyl;
R G6d is, at each occurrence, hydrogen;
G 1 is phenyl optionally substituted with 1 C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, carboxy, halogen, hydroxy, hydroxy-C 1 -C 6 -alkyl, R G1b O 2 C—, R G1a HN(O)C—, (R G1a ) 2 N(O)C—, G 1a C(O)—, G 1b HN(O)C—, or G 1b CH 2 O—;
G 1a is a 4-6-membered heterocycle;
G 1b is phenyl;
G 4a is phenyl or 5-6-membered heteroaryl optionally substituted with 1 or 2 C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, amido, carboxy, halogen, hydroxy, R G4a O 2 C—, (R G4a ) 2 NC(O)—, or G 4a1 -;
G 4a1 is 5-6-membered heteroaryl optionally substituted with 1 C 1 -C 6 -alkyl;
G 4b is a 4-6-membered heterocycle;
G 6a is C 6 -C 10 -aryl or 5-10-membered heteroaryl optionally substituted with 1 or 2 C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, amino, halogen, hydroxy, hydroxyC 1 -C 6 -alkyl, R G6a C(O)—, R G6a O 2 C—, HO 2 C—(CR a R b ) r —, R G6a O 2 C—(CR a R b ) r —, (R G6b ) 2 N(O)C—(CR a R b ) r —, R G6a CO 2 —(CR a R b ) r —, G 6c -, or G 6d -;
G 6b is 4-6-membered heterocycle optionally substituted with 1 or 2 C 1 -C 6 -alkyl or oxo;
G 6c is phenyl or 5-6-membered heteroaryl optionally substituted with 1 or 2 C 1 -C 6 -alkyl, amino, C 1 -C 6 -alkylsulfonylamino, halogen, hydroxy, R G6c O 2 C—, or (R G6d ) 2 NC(O)—; and
G 6d is 4-6-membered heterocycle.
7. The compound of claim 4 , or salt thereof, wherein
X is R 1x C(O)—;
Y is G 1 -; and
R 1x is amino.
8. The compound of claim 7 , or salt thereof, wherein
R 4 is hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, or halogen;
R 6 is hydrogen, C 1 -C 6 -alkoxy, hydroxy or G 6a -;
R G1b is, at each occurrence, C 1 -C 4 -alkyl;
G 1 is phenyl optionally substituted with 1 C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, halogen, hydroxy, or R G1b O 2 C—;
G 6a is C 6 -C 10 -aryl or 5-10-membered heteroaryl optionally substituted with 1 or 2 C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, halogen, hydroxy, or G 6c -; and
G 6c is phenyl or 5-6-membered heteroaryl optionally substituted with 1 C 1 -C 6 -alkyl or halogen.
9. The compound of claim 1 , or salt thereof, further defined by the Formula (Ib).
10. The compound of claim 9 , or salt thereof, further defined by the Formula (Ib-1).
11. The compound of claim 10 , or salt thereof, wherein
X is NC— or R 1x C(O)—;
Y is G 1 - or G 1 -(CR a R b )—; and
R 1x is hydroxy, C 1 -C 6 -alkoxy, amino, C 1 -C 6 -alkylamino, C 1 -C 6 -dialkylamino, or C 1 -C 6 -alkylsulfonylamino.
12. The compound of claim 11 , or salt thereof, wherein
X is NC—; and
Y is G 1 -.
13. The compound of claim 12 , or salt thereof, wherein
r is 1, 2 or 3;
R 5 is hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, G R5a -, G R5a -(CR a R b )—, R 5a C(O)—, G R5a C(O)—, hydroxy-C 1 -C 6 -alkyl-C(O)—, R 5a O 2 C—, G R5a O 2 C—, G R5a HNC(O)—, R 5a O 2 CNHCH 2 C(O)—, H 2 NHCH 2 C(O)—, R 5a SO 2 —, or G R5a SO 2 —;
R 6 is hydrogen, C 1 -C 6 -alkoxy, or G 6a -;
R a and R b are, at each occurrence, hydrogen;
R G1b is, at each occurrence, C 1 -C 4 -alkyl;
R 5a is, at each occurrence, C 1 -C 4 -alkyl;
R G6d is, at each occurrence, hydrogen;
G 1 is phenyl optionally substituted with 1 or 2 C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, carboxy, halogen, hydroxy, or R G1b O 2 C—;
G R5a is phenyl or 5-6-membered heteroaryl;
G 6a is C 6 -C 10 -aryl or 5-10-membered heteroaryl optionally substituted with 1 or 2 C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, amino, C 1 -C 6 -alkylsulfonylamino, carboxy, halogen, hydroxy, hydroxyC 1 -C 6 -alkyl, HO 2 C—(CR a R b ) r — or G 6c -; and
G 6c is phenyl or 5-6-membered heteroaryl optionally substituted with 1 or 2 C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, amino, C 1 -C 6 -alkylsulfonylamino, di(C 1 -C 6 -alkylsulfonyl)amino, C 1 -C 6 -alkylsulfonylaminoC 1 -C 6 -alkyl, carboxy, cyano, halogen, hydroxy, hydroxyC 1 -C 6 -alkyl, and (R G6d ) 2 NC(O)—.
14. The compound of claim 11 , or salt thereof, wherein
X is NC— or R 1x C(O)—;
Y is G 1 -(CR a R b )—;
R 5 is hydrogen, C 1 -C 6 -alkyl, R 5a C(O)— or R 5a SO 2 —;
R 6 is hydrogen or G 6a -;
R a and R b are, at each occurrence, hydrogen;
R 1x is amino;
R 5a is, at each occurrence, C 1 -C 4 -alkyl;
G 1 is phenyl optionally substituted with 1 or 2 C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, carboxy, halogen, hydroxy, or R G1b O 2 C—; and
G 6a is C 6 -C 10 -aryl or 5-10-membered heteroaryl optionally substituted with 1 or 2 C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -alkylsulfonylamino, carboxy or halogen.
15. The compound of claim 1 , or salt thereof, further defined by the Formula (Ic).
16. The compound of claim 15 , or salt thereof, further defined by the Formula (IC-1).
17. The compound of claim 16 , or salt thereof, wherein,
q is 1;
X is NC—;
Y is G 1 -;
R 3 is hydrogen, C 1 -C 6 -alkyl, or G 3a -(CR a R b ) q —;
R 6 is hydrogen or G 6a -;
R a and R b are, at each occurrence, hydrogen;
R G1a is, at each occurrence, independently hydrogen or C 1 -C 4 -alkyl;
R G1b is, at each occurrence, C 1 -C 4 -alkyl;
G 1 is phenyl optionally substituted with 1 C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, carboxy, halogen, hydroxy, hydroxy-C 1 -C 6 -alkyl, R G1b O 2 C—, R G1a HN(O)C—, (R G1a ) 2 N(O)C—, G 1a C(O)—, G 1b HN(O)C—, or G 1b CH 2 O;
G 1a is a 4-6-membered heterocycle;
G 1b is phenyl;
G 3a is phenyl or 5-6-membered heteroaryl optionally substituted with 1 or 2 C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy or halogen; and
G 6a is C 6 -C 10 -aryl or 5-10-membered heteroaryl optionally substituted with 1 or 2 C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy or halogen.
18. The compound of claim 16 , or salt thereof, wherein,
q is 1;
X is NC—;
Y is G 1 -(CR a R b )—;
R 3 is hydrogen, C 1 -C 6 -alkyl, or G 3a -(CR a R b ) q —;
R 6 is hydrogen or G 6a -;
R a and R b are, at each occurrence, hydrogen;
R G1a is, at each occurrence, independently hydrogen or C 1 -C 4 -alkyl;
R G1b is, at each occurrence, C 1 -C 4 -alkyl;
G 1 is phenyl optionally substituted with 1 C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, carboxy, halogen, hydroxy, hydroxy-C 1 -C 6 -alkyl, R G1b O 2 C—, R G1a HN(O)C—, (R G1a ) 2 N(O)C—, G 1a C(O)—, G 1b HN(O)C—, or G 1b CH 2 O;
G 1a is a 4-6-membered heterocycle;
G 1b is phenyl;
G 3a is phenyl or 5-6-membered heteroaryl optionally substituted with 1 or 2 C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy or halogen; and
G 6a is C 6 -C 10 -aryl or 5-10-membered heteroaryl optionally substituted with 1 or 2 C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy or halogen.
19. The compound of claim 1 , or salt thereof, further defined by the Formula (Id).
20. The compound of claim 19 , or salt thereof, further defined by the Formula (Id-1).
21. The compound of claim 20 , or salt thereof, wherein,
X is NC—; and
Y is G 1 -;
r is 1, 2 or 3;
R 5 is hydrogen, C 1 -C 6 -alkyl, G R5a -(CR a R b )—, R 5a C(O)—, G R5a C(O)—, R 5a SO 2 —, or G R5a SO 2 —;
R 6 is hydrogen or G 6a -;
R a and R b are, at each occurrence, hydrogen;
R 5a is, at each occurrence, C 1 -C 4 -alkyl;
G 1 is phenyl optionally substituted with 1 or 2 C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, carboxy, halogen or hydroxy;
G R5a is phenyl or 5-6-membered heteroaryl;
G 6a is C 6 -C 10 -aryl or 5-10-membered heteroaryl optionally substituted with 1 or 2 C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxy, amino, C 1 -C 6 -alkylsulfonylamino, carboxy, halogen, hydroxy, hydroxyC 1 -C 6 -alkyl, HO 2 C—(CR a R b ) r — or G 6c -; and
G 6c is phenyl or 5-6-membered heteroaryl optionally substituted with 1 or 2 C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, amino, C 1 -C 6 -alkylsulfonylamino, di(C 1 -C 6 -alkylsulfonyl)amino, C 1 -C 6 -alkylsulfonylaminoC 1 -C 6 -alkyl, carboxy, cyano, halogen and hydroxy.
22. The compound of claim 1 , or a salt thereof, wherein the compound is selected from the group consisting of:
(6aS,7S,10aR)-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
rac-(5aS,6S,9aR)-2,6-dimethyl-7-oxo-3,9a-diphenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
rac-(5aS,6S,9aR)-1,6-dimethyl-7-oxo-3,9a-diphenyl-4,5,5a,6,7,9a-hexahydro-1H-benzo[g]indazole-8-carbonitrile;
rac-(5aS,6S,9aR)-9a-(4-methoxyphenyl)-2,6-dimethyl-7-oxo-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
rac-(5aS,6S,9aR)-9a-(4-methoxyphenyl)-1,6-dimethyl-7-oxo-4,5,5a,6,7,9a-hexahydro-1H-benzo[g]indazole-8-carbonitrile;
rac-(5aS,6S,9aR)-6-methyl-7-oxo-3,9a-diphenyl-4,5,5a,6,7,9a-hexahydro-1H-benzo[g]indazole-8-carbonitrile;
(7S)-7-methyl-8-oxo-2,10a-diphenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(7S)-4-methoxy-7-methyl-8-oxo-2,10a-diphenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(7S,10aS)-2-anilino-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-4-methoxy-2-(2-methoxyphenyl)-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-7-methyl-8-oxo-10a-phenyl-2-(pyridin-3-yl)-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2-(ethylamino)-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-4-methoxy-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2-anilino-4-methoxy-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2-[(4-bromophenyl)amino]-4-methoxy-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2-anilino-7-methyl-8-oxo-10a-phenyl-4-(pyrimidin-5-yl)-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2,7-dimethyl-4-(1-methyl-1H-imidazol-5-yl)-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2,7-dimethyl-4-(2-methyl-1,3-thiazol-5-yl)-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-7-methyl-2-(morpholin-4-yl)-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-4-hydroxy-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2,7-dimethyl-8-oxo-4,10a-diphenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2,7-dimethyl-8-oxo-10a-phenyl-4-(pyrimidin-5-yl)-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-4-(3-furyl)-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6S,9aR)-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(6aS,7S,10aR)-2-(2-fluorophenyl)-4-methoxy-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(5aS,6S,9aR)-1,6-dimethyl-7-oxo-9a-phenyl-3-(pyridin-3-yl)-4,5,5a,6,7,9a-hexahydro-1H-benzo[g]indazole-8-carbonitrile;
(6aS,7S,10aR)-2,7-dimethyl-8-oxo-10a-phenyl-4-(pyridin-4-yl)-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6S,9aR)-2-acetyl-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(6aS,7S,10aR)-7-methyl-8-oxo-10a-phenyl-2-(pyridin-4-yl)-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2-(diethylamino)-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2-(2-fluorophenyl)-4-isopropoxy-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
methyl (6S,9aR)-8-cyano-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-2-carboxylate;
rac-(6aS,7S,10aR)-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2,7-dimethyl-8-oxo-10a-phenyl-4-(1H-pyrazol-4-yl)-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2,7-dimethyl-4-(1-methyl-1H-pyrazol-4-yl)-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6S,9aR)-6-methyl-2-(methylsulfonyl)-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
phenyl (6S,9aR)-8-cyano-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-2-carboxylate;
(6S,9aR)-2-benzoyl-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
tert-butyl {2-[(6S,9aR)-8-cyano-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazol-2-yl]-2-oxoethyl}carbamate;
(6S,9aR)-6-methyl-7-oxo-9a-phenyl-2-(1,3-thiazol-4-ylcarbonyl)-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(6S,9aR)-6-methyl-7-oxo-9a-phenyl-2-(phenylsulfonyl)-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(6S,9aR)-2-glycoloyl-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(6aS,7S,10aR)-4-(3-methoxyphenyl)-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7, 8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2,7-dimethyl-4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2,7-dimethyl-8-oxo-10a-phenyl-4-(quinolin-6-yl)-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
2-{3-[(6aS,7S,10aR)-9-cyano-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8, 0a-hexahydrobenzo[h]quinazolin-4-yl]phenyl}ethyl acetate;
(6aS,7S,10aR)-4-[3-(2-hydroxyethyl)phenyl]-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6S,9aR)-8-cyano-6-methyl-7-oxo-9a-phenyl-N-(pyridin-3-yl)-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-2-carboxamide;
(6aS,7S,10aR)-7-methyl-8-oxo-10a-phenyl-2-(pyrimidin-5-yl)-5,6,6a,7, 8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-10a-(4-fluorophenyl)-7-methyl-8-oxo-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-10a-(4-fluorophenyl)-7-methyl-8-oxo-2-(pyridin-3-yl)-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6S,9aR)-2,6-dimethyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(5 aS,6S,9aR)-9a-(3-fluorophenyl)-6-methyl-7-oxo-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(5 aS,6S,9aR)-9a-(4-fluorophenyl)-6-methyl-7-oxo-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(6aS,7S,10aR)-10a-(3-fluorophenyl)-7-methyl-8-oxo-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(5aS,6S,9aR)-2-benzyl-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(5aS,6S,9aR)-1-benzyl-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-1H-benzo[g]indazole-8-carbonitrile;
(5aS,6S,9aR)-9a-(4-methoxyphenyl)-6-methyl-7-oxo-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
methyl 3-[(6aS,7S,10aR)-9-cyano-7-methyl-8-oxo-6,6a,7,8-tetrahydrobenzo[h]quinazolin-10a(5H)-yl]benzoate;
3-[(6aS,7S,10aR)-9-cyano-7-methyl-8-oxo-6,6a,7,8-tetrahydrobenzo[h]quinazolin-10a(5H)-yl]benzoic acid;
3-[(6aS,7S,10aR)-9-cyano-7-methyl-8-oxo-6,6a,7,8-tetrahydrobenzo[h]quinazolin-10a(5H)-yl]benzamide;
methyl 3-[(5aS,6S,9aR)-8-cyano-6-methyl-7-oxo-2,4,5,5a,6,7-hexahydro-9aH-benzo[g]indazol-9a-yl]benzoate;
methyl 4-[(5aS,6S,9aR)-8-cyano-6-methyl-7-oxo-2,4,5,5a,6,7-hexahydro-9aH-benzo[g]indazol-9a-yl]benzoate;
methyl 4-[(6aS,7S,10aR)-9-cyano-7-methyl-8-oxo-6,6a,7,8-tetrahydrobenzo[h]quinazolin-10a(5H)-yl]benzoate;
(5aS,6S,9aR)-1-(4-bromobenzyl)-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-1H-benzo[g]indazole-8-carbonitrile;
4-[(6aS,7S,10aR)-9-cyano-7-methyl-8-oxo-6,6a,7,8-tetrahydrobenzo[h]quinazolin-10a(5H)-yl]benzoic acid;
(6aS,7S,10aR)-10a-(4-methoxyphenyl)-2,7-dimethyl-8-oxo-4-(pyrimidin-5-yl)-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-10a-(4-fluorophenyl)-2,7-dimethyl-8-oxo-4-(pyrimidin-5-yl)-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-10a-(3-fluorophenyl)-2,7-dimethyl-8-oxo-4-(pyrimidin-5-yl)-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-10a-(4-methoxyphenyl)-7-methyl-8-oxo-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
3-[(5aS,6S,9aR)-8-cyano-6-methyl-7-oxo-2,4,5,5a,6,7-hexahydro-9aH-benzo[g]indazol-9a-yl]benzoic acid;
(6S,9aR)-9a-(4-hydroxyphenyl)-6-methyl-7-oxo-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(6aS,7S,10aR)-7-methyl-8-oxo-10a-[4-(pyrrolidin-1-ylcarbonyl)phenyl]-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2-(2,6-difluorophenyl)-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
methyl 4-[(6aS,7S,10aR)-9-cyano-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazolin-2-yl]benzoate;
(6aS,7S,10aR)-4-(1-acetyl-1H-pyrazol-4-yl)-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
4-[(6aS,7S,10aR)-9-cyano-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazolin-2-yl]benzoic acid;
(6S,9aR)-9a-(3-fluorophenyl)-3-[3-(3-hydroxypropyl)phenyl]-6-methyl-7-oxo-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(6aS,7S,10aR)-4-[4-(4-bromo-1H-pyrazol-5-yl)phenyl]-10a-(4-methoxyphenyl)-2,7-dimethyl-8-oxo-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-10a-(4-methoxyphenyl)-2,7-dimethyl-8-oxo-4-[4-(1H-pyrazol-5-yl)phenyl]-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-4-[4-(4-bromo-1H-pyrazol-5-yl)phenyl]-10a-(4-fluorophenyl)-2,7-dimethyl-8-oxo-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(5aS,6S,9aR)-9a-(4-fluorophenyl)-2-glycyl-6-methyl-7-oxo-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(6aS,7S,10aR)-10a-(4-fluorophenyl)-2,7-dimethyl-8-oxo-4-[4-(1H-pyrazol-5-yl)phenyl]-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-7-methyl-8-oxo-10a-phenyl-2-(pyrazin-2-yl)-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2-tert-butyl-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6S,9aR)-6-methyl-7-oxo-9a-phenyl-3-(pyridin-3-yl)-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(6S,9aR)-6-methyl-7-oxo-9a-phenyl-3-(pyrimidin-5-yl)-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(6S,9aR)-3-(3-hydroxyphenyl)-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(6S,9aR)-6-methyl-3-(1-methyl-1H-pyrazol-4-yl)-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(6aS,7S,10aR)-4-(1H-benzimidazol-5-yl)-10a-(4-methoxyphenyl)-2,7-dimethyl-8-oxo-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-4-(1H-benzimidazol-5-yl)-10a-(4-fluorophenyl)-2,7-dimethyl-8-oxo-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-4-(3-bromo-1H-indazol-7-yl)-10a-(4-fluorophenyl)-2,7-dimethyl-8-oxo-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-10a-(4-fluorophenyl)-4-(1H-indazol-7-yl)-2,7-dimethyl-8-oxo-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-4-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-10a-(4-fluorophenyl)-2,7-dimethyl-8-oxo-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
3-[(6aS,7S,10aR)-9-cyano-7-methyl-8-oxo-6,6a,7,8-tetrahydrobenzo[h]quinazolin-10a(5H)-yl]-N-phenylbenzamide;
3-[(6aS,7S,10aR)-9-cyano-7-methyl-8-oxo-6,6a,7,8-tetrahydrobenzo[h]quinazolin-10a(5H)-yl]-N-propylbenzamide;
(5aS,6S,9aR)-2,6-dimethyl-7-oxo-9a-phenyl-3-(pyridazin-4-yl)-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
methyl 4-[(6aS,7S,10aR)-9-cyano-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazolin-4-yl]-1H-pyrazole-1-carboxylate;
methyl 3-[(6aS,7S,10aR)-9-cyano-7-methyl-8-oxo-2-phenyl-6,6a,7,8-tetrahydrobenzo[h]quinazolin-10a(5H)-yl]benzoate;
3-[(6aS,7S,10aR)-9-cyano-7-methyl-8-oxo-2-phenyl-6,6a,7,8-tetrahydrobenzo[h]quinazolin-10a(5H)-yl]benzoic acid;
methyl 3-[(6aS,7S,10aR)-9-cyano-2-[4-(methoxycarbonyl)phenyl]-7-methyl-8-oxo-6,6a,7,8-tetrahydrobenzo[h]quinazolin-10a(5H)-yl]benzoate;
(6aS,7S,10aR)-2-chloro-4-methoxy-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2,4-dimethoxy-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
3-[(6aS,7S,10aR)-2-(4-carboxyphenyl)-9-cyano-7-methyl-8-oxo-6,6a,7,8-tetrahydrobenzo[h]quinazolin-10a(5H)-yl]benzoic acid;
(3R,3aR,5aS,6S,9aR)-2,6-dimethyl-7-oxo-3,9a-diphenyl-3,3a,4,5,5a,6,7,9a-octahydro-2H-benzo[g]indazole-8-carbonitrile;
(6S,9aR)-3-(6-aminopyridin-3-yl)-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(6aS,7S,10aR)-4-(imidazo[1,2-a]pyridin-6-yl)-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-4-(4-hydroxyphenyl)-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-4-(3-hydroxyphenyl)-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-4-[3-(3-hydroxypropyl)phenyl]-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2-(5-bromo-2-hydroxyphenyl)-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
N-{4-[(6S,9aR)-8-cyano-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazol-3-yl]phenyl}methanesulfonamide;
N-{3-[(6S,9aR)-8-cyano-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazol-3-yl]phenyl}methanesulfonamide;
(6aS,7S,10aR)-2-(4-hydroxyphenyl)-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6S,9aR)-3-[4-(2-hydroxyethyl)phenyl]-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(6S,9aR)-3-[3-(2-hydroxyethyl)phenyl]-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(6S,9aR)-3-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(6aS,7S,10aR)-4-(4′-aminobiphenyl-3-yl)-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-4-(4′-hydroxybiphenyl-3-yl)-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-10a-[4-(benzyloxy)phenyl]-7-methyl-8-oxo-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-10a-(4-hydroxyphenyl)-7-methyl-8-oxo-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2,7-dimethyl-8-oxo-10a-phenyl-4-[4-(pyridin-4-yl)phenyl]-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6S,9aR)-3-[3-(3-hydroxypropyl)phenyl]-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
N-{3′-[(6aS,7S,10aR)-9-cyano-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazolin-4-yl]biphenyl-3-yl}methanesulfonamide;
3-{3-[(6aS,7S,10aR)-9-cyano-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazolin-4-yl]phenyl}propyl acetate;
(6S,9aR)-3-[5-(hydroxymethyl)pyridin-3-yl]-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(6aS,7S,10aR)-4-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-10a-[3-(benzyloxy)phenyl]-7-methyl-8-oxo-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2,7-dimethyl-8-oxo-10a-phenyl-4-[4-(pyrimidin-5-yl)phenyl]-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2,7-dimethyl-8-oxo-10a-phenyl-4-(pyrimidin-5-yl)-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carboxamide;
(6aS,7S,10aR)-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carboxamide;
(6aS,7S,10aR)-4-(5-bromo-6-hydroxypyridin-3-yl)-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-4-(6-hydroxypyridin-3-yl)-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
methyl 3′-[(6aS,7S,10aR)-9-cyano-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazolin-4-yl]biphenyl-4-carboxylate;
3′-[(6aS,7S,10aR)-9-cyano-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazolin-4-yl]biphenyl-4-carboxamide;
4-[(6aS,7S,10aR)-9-cyano-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazolin-2-yl]benzamide;
(6aS,7S,10aR)-10a-(3-hydroxyphenyl)-7-methyl-8-oxo-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
4-[(6aS,7S,10aR)-9-cyano-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazolin-2-yl]-N,N-dimethylbenzamide;
(6aS,7S,10aR)-2,7-dimethyl-4-[4-(1-methyl-1H-imidazol-5-yl)phenyl]-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(5aS,6S,9aR)-6-methyl-7-oxo-9a-phenyl-3-(pyridazin-4-yl)-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
{4-[(6S,9aR)-8-cyano-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazol-3-yl]-1H-pyrazol-1-yl}acetic acid;
methyl 3-[(6aS,7S,10aR)-9-carbamoyl-7-methyl-8-oxo-6,6a,7,8-tetrahydrobenzo[h]quinazolin-10a(5H)-yl]benzoate;
(5aS,6S,9aR)-2,6-dimethyl-7-oxo-9a-phenyl-3-[4-(pyridin-4-yl)phenyl]-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(5aS,6S,9aR)-2,6-dimethyl-7-oxo-9a-phenyl-3-[4-(pyrimidin-5-yl)phenyl]-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(6aS,7S,10aR)-2,7-dimethyl-8-oxo-10a-phenyl-4-[4-(pyrimidin-5-yl)phenyl]-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carboxamide;
(6aS,7S,10aR)-4-[3-bromo-4-(morpholin-4-yl)phenyl]-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-2,7-dimethyl-8-oxo-10a-phenyl-4-(pyridin-3-ylamino)-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(5aS,6S,9aR)-3-(3-bromophenyl)-2,6-dimethyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(5aS,6S,9aR)-3-(4′-aminobiphenyl-3-yl)-2,6-dimethyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
N-{3′-[(5aS,6S,9aR)-8-cyano-2,6-dimethyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazol-3-yl]biphenyl-3-yl}methanesulfonamide;
(5aS,6S,9aR)-2,6-dimethyl-7-oxo-9a-phenyl-3-[3-(pyridazin-4-yl)phenyl]-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
N-{3′-[(5aS,6S,9aR)-8-cyano-2,6-dimethyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazol-3-yl]biphenyl-4-yl}-N-(methylsulfonyl)methanesulfonamide;
(5aS,6S,9aR)-3-[3-(2-methoxypyrimidin-5-yl)phenyl]-2,6-dimethyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
methyl 3-{3-[(6aS,7S,10aR)-9-cyano-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazolin-4-yl]phenyl}propanoate;
3-{3-[(6aS,7S,10aR)-9-cyano-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazolin-4-yl]phenyl}propanoic acid;
3-{3-[(6aS,7S,10aR)-9-cyano-2,7-dimethyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazolin-4-yl]phenyl}propanamide;
(5aS,6S,9aR)-3-[1-(4-cyanophenyl)-1H-pyrazol-4-yl]-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(5aS,6S,9aR)-6-methyl-7-oxo-9a-phenyl-3-[1-(pyridin-3-yl)-1H-pyrazol-4-yl]-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(5aS,6S,9aR)-6-methyl-7-oxo-9a-phenyl-3-[1-(pyridin-4-yl)-1H-pyrazol-4-yl]-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
rac-(5aS,6S,9aR)-2,6-dimethyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
rac-(5aS,6S,9aR)-1,6-dimethyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-1H-benzo[g]indazole-8-carbonitrile;
rac-(5aS,6S,9aR)-9a-benzyl-2,6-dimethyl-7-oxo-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
rac-(5aS,6S,9aR)-9a-benzyl-1,6-dimethyl-7-oxo-4,5,5a,6,7,9a-hexahydro-1H-benzo[g]indazole-8-carbonitrile;
rac-(5aS,6S,9aR)-9a-benzyl-2,6-dimethyl-7-oxo-3-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
rac-(5aS,6S,9aR)-9a-benzyl-2,6-dimethyl-7-oxo-3-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carboxamide;
3′-[(5aS,6S,9aR)-8-cyano-2,6-dimethyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazol-3-yl]biphenyl-3-carboxylic acid;
(5aS,6S,9aR)-2,6-dimethyl-7-oxo-9a-phenyl-3-[3-(1H-pyrazol-4-yl)phenyl]-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
N-({3′-[(5aS,6S,9aR)-8-cyano-2,6-dimethyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazol-3-yl]biphenyl-4-yl}methyl)methanesulfonamide;
N-{3′-[(5aS,6S,9aR)-8-cyano-2,6-dimethyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazol-3-yl]biphenyl-4-yl}methanesulfonamide;
(5aS,6S,9aR)-3-(4′-hydroxybiphenyl-3-yl)-2,6-dimethyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
3′-[(5aS,6S,9aR)-8-cyano-2,6-dimethyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazol-3-yl]biphenyl-4-carboxamide;
(6aS,7S,10aR)-2,7-dimethyl-8-oxo-10a-phenyl-4-(pyridazin-4-yl)-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-7-methyl-2-[4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
(6aS,7S,10aR)-10a-(4-methoxyphenyl)-2,7-dimethyl-4-(1-methyl-1H-imidazol-5-yl)-8-oxo-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile;
methyl 4-[(6aS,7S,10aR)-9-cyano-2,7-dimethyl-4-(1-methyl-1H-imidazol-5-yl)-8-oxo-6,6a,7,8-tetrahydrobenzo[h]quinazolin-10a(5H)-yl]benzoate;
methyl 4-[(6aS,7S,10aR)-4-(4-bromo-1-methyl-1H-imidazol-5-yl)-9-cyano-2,7-dimethyl-8-oxo-6,6a,7,8-tetrahydrobenzo[h]quinazolin-10a(5H)-yl]benzoate;
(5aS,6S,9aR)-2,6-dimethyl-7-oxo-9a-phenyl-3-(pyrimidin-5-yl)-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile;
(5aS,6S,9aR)-2,6-dimethyl-7-oxo-9a-phenyl-3-(pyridin-3-yl)-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile; and
(5aS,6S,9aR)-1,6-dimethyl-7-oxo-9a-phenyl-3-(pyrimidin-5-yl)-4,5,5a,6,7,9a-hexahydro-1H-benzo[g]indazole-8-carbonitrile.
23. The compound, or a salt thereof, of claim 1 , wherein the salt is a pharmaceutically acceptable salt.
24. A pharmaceutical composition comprising a therapeutically effective amount of claim 1 , or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.