Carbazole compounds and therapeutic uses of the compounds

1. A compound having a structural formula:

wherein R a is selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR e , N(R e ) 2 , and SR e ; alternatively, either R a and R 1 or NR e and R 1 together with the carbon atoms to which they are attached form a five or six-membered aliphatic carbocyclic or heterocyclic ring;

R b is selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR e , N(R e ) 2 , and SR e , alternatively, either R b and R 6 or NR e and R 6 together with the carbon atoms to which they are attached form a five or six-membered aliphatic carbocyclic ring or a five or six-membered aliphatic carbocyclic or heterocyclic ring;

R c is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 hydroxyalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, and C(═O)R e , or R c and R d are taken together to form a five, six, or seven-membered aliphatic ring, optionally containing an oxygen atom;

R d is selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, and C(═O)R e , or R d and R 7 together with the atoms to which they are attached form a five or six-membered aliphatic ring;

R e , independently, is selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, or two R e groups taken together with a nitrogen to which they are attached to form a five or six-membered aliphatic ring;

R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 , independently, are selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, halo, OR e , C(═O)R e , C(═O)OR e , OC(═O)R e , C(═O)N(R e ) 2 , C(═O)NR e SO 2 R e , N(R e ) 2 , NR e C(═O)R e ,

NR e C(═O)N(R e ) 2 , CN, NO 2 , CF 3 , OCF 3 , SR e , SOR e , SO 2 R e , SO 2 N(R e ) 2 , and OSO 2 CF 3 ;

R 7 is selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; and

n is 1, 2, 3, 4, or 5,

or a pharmaceutically acceptable salt or hydrate thereof.

2. The compound of claim 1 wherein the compound has a structural formula (Ia):

wherein R a is C 1-3 alkyl, C 1-4 haloalkyl, C 3-5 cycloalkyl, N(R e ) 2 , or OR e , or R a and R 1 together with the carbon atoms to which they are attached form a five or six-membered aliphatic carbocyclic ring;

R b is C 1 alkyl, C 1-4 haloalkyl, C 3-5 cycloalkyl, N(R e ) 2 , or OR e , or R b and R 6 together with the carbon atoms to which they are attached form a five or six-membered aliphatic carbocyclic ring or a five or six-membered aliphatic ring containing one nitrogen atom;

R c is C 1-6 alkyl, C 3-5 cycloalkyl, or C 1-3 hydroxyalkyl;

R d is hydrogen, C 1-4 alkyl, or C 3-5 cycloalkyl, or R d and R 7 together with the atoms to which they are attached form a five or six-membered aliphatic ring containing one nitrogen atom, or R c and R d are taken together to form a six- or seven-membered aliphatic ring, optionally containing an oxygen atom;

R e , independently, is hydrogen or C 1-3 alkyl;

R 1 is hydrogen or C 1-3 alkyl;

R 2 is hydrogen, hydroxy, or C 1-3 alkoxy;

R 3 and R 4 , independently, are hydrogen or C 1-3 alkyl;

R 5 is hydrogen, hydroxy, C 1-3 alkoxy, or halo;

R 6 is hydrogen, C 1-3 alkyl, C 1-3 alkoxy, or halo;

R 7 is hydrogen or C 1-3 alkyl; and

n is 1, 2, 3, 4, or 5,

or a pharmaceutically acceptable salt or hydrate thereof.

3. The compound of claim 1 wherein the compound has a structural formula (Ib):

wherein R a is methyl, ethyl, n-propyl, cyclopropyl, NH(CH 3 ), or OCH 3 , or R a and R 1 together with the carbon atoms to which they are attached form a five-membered aliphatic carbocyclic ring;

R b is methyl, ethyl, n-propyl, cyclopropyl, NH(CH 3 ), or OCH 3 , or R b and R 6 together with the carbon atoms to which they are attached form a five-membered aliphatic carbocyclic ring or a five-membered aliphatic ring containing one nitrogen atom;

R c is methyl, ethyl, n-propyl, isopropyl, cyclobutyl, or 2-hydroxyethyl;

R d is hydrogen, methyl, ethyl, or cyclobutyl, or R d and R 7 together with the atoms to which they are attached form a five-membered aliphatic ring containing one nitrogen atom; or R c and R d are taken together to form a morpholino moiety; a piperidinyl moiety; or a

moiety;

R 1 is hydrogen;

R 2 is hydrogen, hydroxy, or methoxy;

R 3 and R 4 are hydrogen;

R 5 is hydrogen, hydroxy, methoxy, or fluoro;

R 6 is hydrogen, methyl, methoxy or fluoro;

R 7 is hydrogen; and

n is 1 or 2,

or a pharmaceutically acceptable salt or hydrate thereof.

4. A compound having a structural formula:

wherein R f is selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, and C(═O)R h ;

R g is selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, and C(═O)R h , or R g and R 8 together with the atoms to which they are attached form a five or six-membered aliphatic ring;

R h , independently, is selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, or two R h groups taken together with a nitrogen to which they are attached to form a five or six-membered aliphatic ring;

R 8 is selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;

R 9 , R 10 , R 11 , R 12 , R 13 , and R 14 , independently, are selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, halo, OR h , C(═O)R h , C(═O)OR h , OC(═O)R h , C(═O)N(R h ) 2 , C(═O)NR h SO 2 R h , N(R h ) 2 , NR h C(═O)R h , NR h C(═O)N(R h ) 2 , CN, CF 3 , OCF 3 , SR h , SOR h , SO 2 R h , SO 2 N(R h ) 2 , and OSO 2 CF 3 ;

p is 0, 1 , 2, 3, 4, or 5,

with the proviso that when p is 2, one of R f and R g is different from ethyl,

or a pharmaceutically acceptable salt or hydrate thereof.

5. The compound of claim 4 wherein the compound has a structural formula (IIa):

wherein R f is C 1-6 alkyl;

R g is hydrogen or C 1-4 alkyl, or R g and R 8 together with the atoms to which they are attached form a five or six-membered aliphatic ring containing one nitrogen atom;

R 9 is hydrogen or C 1-3 alkyl;

R 10 is hydrogen, hydroxy, or C 1-3 alkoxy;

R 11 and R 12 , independently, are hydrogen or C 1-3 alkyl;

R 13 is hydrogen, hydroxy, C 1-3 alkoxy, or halo;

R 14 is hydrogen, C 1-3 alkyl, or C 1-3 alkoxy;

R 8 is hydrogen or C 1-3 alkyl; and

p is 0, 1, 2, 3, 4, or 5,

with the proviso that when p is 2, one of R f and R g is different from ethyl,

or a pharmaceutically acceptable salt or hydrate thereof.

6. The compound of claim 4 wherein the compound has a structural formula (IIb):

wherein R f is methyl or ethyl;

R g is hydrogen or methyl or R g and R 8 together with the atoms to which they are attached form a five-membered aliphatic ring containing one nitrogen atom;

R 8 is hydrogen; and

p is 1 or 2,

or a pharmaceutically acceptable salt or hydrate thereof.

7. The compound of claim 1 wherein R a is methyl, ethyl, NH(CH 3 ), OCH 3 , or forms a five-membered aliphatic ring with R 1 , R b is methyl, ethyl, NH(CH 3 ), OCH 3 , forms a five-membered aliphatic ring with R 6 , or forms a five-membered, nitrogen containing, aliphatic ring with R 6 , and R d is hydrogen, methyl, ethyl, or forms a five-membered aliphatic ring with R 7 .

8. The compound of claim 1 wherein R 1 is hydrogen or forms a five-membered aliphatic ring with R a , R 2 is hydrogen or hydroxy, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen or hydroxy, R 6 is hydrogen, forms a five-membered aliphatic ring with R b , or forms a five-membered, nitrogen-containing aliphatic ring with R b , R 7 is hydrogen or forms a five-membered ring with R d , and n is 2 or 3.

9. The compound of claim 4 wherein R f is methyl or ethyl, R g is hydrogen, methyl, ethyl, or forms a five-membered, nitrogen containing aliphatic ring with R f and R 8 , or R 8 is hydrogen; R 9 , R 10 , R 11 , R 12 , R 13 , and R 14 are hydrogen, p is 2 or 3.

10. A compound having a structural formula:

11. A compound selected from the group consisting of

12. A compound selected from the group consisting of

13. A compound having a structural formula