Granted Patent B2

US 7,964,608 · App. 12/532,861 · Granted Jun 21, 2011

Abstract

Claims (334)

1. A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein

A 1 is O or S;

A 2 is O or S;

U is N;

V is C—(CH 2 ) v R V ;

W is C—(CH 2 ) w R W ;

X is C—(CH 2 ) x R X ;

Y is C—(CH 2 ) y R Y ;

Z is C—(CH 2 ) z R Z ;

R 1 is —(CH 2 ) q R Q ;

R 2 is —(CH 2 ) s R S ;

wherein

each of q, s, w, x, y, and z individually is 0, 1, 2, 3, or 4;

v is zero;

R Q is selected from the group consisting of:

alkyl,

cycloalkyl,

phenyl,

benzyl,

tetrahydrofuranyl,

tetrahydropyranyl,

pyrrolidinyl,

piperidinyl, and

—OR 8 , wherein

the cycloalkyl is optionally substituted with one or more R c ;

the phenyl and benzyl are each independently optionally substituted with one or more R a ; and

the tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl and piperidinyl are each independently optionally substituted with one or more R hc ;

R V is chloro or —OCH 3 ;

each of R S , R W , R X , R Y , and R Z is independently selected from the group consisting of

alkyl;

alkenyl;

alkynyl;

aryl;

aryl substituted with one or more R a ;

azido;

cyano;

cycloalkyl;

cycloalkyl substituted with one or more R c ;

fused cycloalkylaryl substituted with one or more R f1 ;

fused arylcycloalkyl substituted with one or more R f2 ;

fused heterocyclyaryl substituted with one or more R f3 ;

fused arylheterocyclyl substituted with one or more R f4 ;

fused cycloalkylheteroaryl substituted with one or more R f5 ;

fused heteroarylcycloalkyl substituted with one or more R f6 ;

fused heterocyclylheteroaryl substituted with one or more R f7 ;

halogen;

haloalkyl;

heterocyclyl;

heterocyclyl substituted with one or more R hc ;

heteroaryl;

heteroaryl substituted with one or more R ha ;

hydrogen;

—NR 3 R 4 ;

—C(O)NR 3 R 4 ;

—C(O)R 5 ;

—C(O) 2 R 6 ;

—S(O) j R 7 ;

—OR 8 ; and

nitro;

wherein

each of R 3 and R 4 is independently selected from the group consisting of H, acyl, alkyl, alkoxy, alkoxyalkyl, alkylsulfonyl, aryl, cycloalkyl, heterocyclyl and heteroaryl;

j is 0, 1, or 2;

each R 5 , R 6 , R 7 , and R 8 is independently selected from the group consisting of

hydrogen;

alkyl;

alkenyl;

alkynyl;

alkoxy;

aryl;

aryl substituted with one or more R a ;

cycloalkyl;

cycloalkyl substituted with one or more R c ;

halogen;

haloalkyl;

heterocyclyl;

heterocyclyl substituted with one or more R hc ;

heteroaryl; and

heteroaryl substituted with one or more R ha ;

wherein each of R a , R c , R f1 , R f2 , R f3 , R f4 , R f5 , R f6 , R f7 , R hc , and R ha is independently selected from the group consisting of acyl, alkyl, alkenyl, alkynyl, alkoxy, amide, amino, aryl, cyano, cycloalkyl, halogen, haloalkyl, haloalkoxy, heteroaryl, hydroxy, nitro, —C(O)OR 9 , —SO 2 R 10 —SR 11 , —C(O)R 12 , —C(O)NR 13 , —NH—SO 2 —R 14 , —SO 2 —NR 15 R 16 , and —SO 2 —CH 2 —SO 2 —CH 3 ; and wherein

each of R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , and R 16 ,is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl, and heteroaryl.

2. The compound according to claim 1 , wherein A 1 and A 2 are each O.

3. The compound according to claim 1 , wherein R x is halogen or hydrogen and x is zero.

4. The compound according to claim 1 , wherein R 1 is cycloalkyl or cycloalkyl substituted with one or more R c .

5. The compound according to claim 4 , wherein the cycloalkyl is cyclopentyl or cyclohexyl substituted with one or more R c .

6. The compound according to claim 1 , wherein R S is selected from the group consisting of

hydrogen,

alkyl,

cycloalkyl,

phenyl,

benzyl,

furanyl,

thiophenyl,

isoxazolyl,

benzodioxolyl, and

indanyl,

—C(O)R 5 ,

—C(O) 2 R 6 , and

—OR 8 , wherein

the cycloalkyl is optionally substituted with one or more R c ;

the phenyl and benzyl are each independently optionally substituted with one or more R a ; and

the furanyl, thiophenyl, isoxazolyl, benzodioxolyl, and indanyl, are each independently optionally substituted with one or more R ha .

7. The compound according to claim 6 , wherein R 2 is phenyl substituted with one or more R a , and R a is halogen.

8. The compound according to claim 7 , wherein R 2 is 3-chlorophenyl.

9. The compound according to claim 8 , wherein R 1 is a 4-substituted cyclohexyl group.

10. The compound according to claim 9 , wherein R 1 is trans-4-cyclohexanecarboxylic acid.

11. The compound according to claim 10 , wherein the compound is in the form of a hydrochloric acid salt.

12. A pharmaceutical composition comprising:

a compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein

A 1 is O or S;

A 2 is O or S;

U is N;

V is C—(CH 2 ) v R V ;

W is C—(CH 2 ) n R W ;

X is C—(CH 2 ) x R X ;

Y is C—(CH 2 ) y R Y ;

Z is C—(CH 2 ) z R Z ;

R 1 is —(CH 2 ) q R Q ;

R 2 is —(CH 2 ) s R S ;

wherein

each of q, s, v, w, x, y, and z individually is 0, 1, 2, 3, or 4;

R Q is selected from the group consisting of:

alkyl,

cycloalkyl,

phenyl,

benzyl,

tetrahydrofuranyl,

tetrahydropyranyl,

pyrrolidinyl,

piperidinyl, and

—OR 8 , wherein

the cycloalkyl is optionally substituted with one or more R c ;

the phenyl and benzyl are each independently optionally substituted with one or more R a ; and

the tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl and piperidinyl are each independently optionally substituted with one or more R hc ;

each of R S , R V , R W , R X , R Y , and R Z is independently selected from the group consisting of

alkyl;

alkenyl;

alkynyl;

aryl;

aryl substituted with one or more R a ;

azido;

cyano;

cycloalkyl;

cycloalkyl substituted with one or more R c ;

fused cycloalkylaryl substituted with one or more R f1 ;

fused arylcycloalkyl substituted with one or more R f2 ;

fused heterocyclyaryl substituted with one or more R f3 ;

fused arylheterocyclyl substituted with one or more R f4 ;

fused cycloalkylheteroaryl substituted with one or more R f5 ;

fused heteroarylcycloalkyl substituted with one or more R f6 ;

fused heterocyclylheteroaryl substituted with one or more R f7 ;

halogen;

haloalkyl;

heterocyclyl;

heterocyclyl substituted with one or more R hc

heteroaryl;

heteroaryl substituted with one or more R ha ;

hydrogen;

—NR 3 R 4 ;

—C(O)NR 3 R 4 ;

—C(O)R 5 ;

—C(O) 2 R 6 ;

—S(O) J R 7 ;

—OR 8 ; and

nitro;

wherein

each of R 3 and R 4 is independently selected from the group consisting of H, acyl, alkyl, alkoxy, alkoxyalkyl, alkylsulfonyl, aryl, cycloalkyl, heterocyclyl and heteroaryl;

j is 0, 1, or 2;

each R 5 , R 6 , R 7 , and R 8 is independently selected from the group consisting of

hydrogen;

alkyl;

alkenyl;

alkynyl;

alkoxy;

aryl;

aryl substituted with one or more R a ;

cycloalkyl;

cycloalkyl substituted with one or more R c ;

halogen;

haloalkyl;

heterocyclyl;

heterocyclyl substituted with one or more R hc ;

heteroaryl; and

heteroaryl substituted with one or more R ha ;

wherein each of R a , R c , R f1 , R f2 , R f3 , R f4 , R f5 , R f6 , R f7 , R hc and R ha is independently selected from the group consisting of acyl, alkyl, alkenyl, alkynyl, alkoxy, amide, amino, aryl, cyano, cycloalkyl, halogen, haloalkyl, haloalkoxy, heteroaryl, hydroxy, nitro, —C(O)OR 9 , —SO 2 R 10 , —SR 11 , —C(O)R 12 , —C(O)NR 13 , —NH—SO 2 —R 14 , —SO 2 —NR 15 R 16 , and —SO 2 —CH 2 —SO 2 —CH 3 ; and wherein

each of R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , and R 16 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl, and heteroaryl; and

a pharmaceutically acceptable carrier.

13. The pharmaceutical composition according to claim 12 , wherein A 1 and A 2 are each O.

14. A method of synthesizing a compound having the formula

comprising mixing a compound of formula

and a compound of formula ONC—R 2 and a base,

wherein

R 1 is —(CH 2 ) q R Q ;

R 2 is —(CH 2 ) s R S ;

R 3 is —(CH 2 ) v R V ;

wherein

each of q, s, and v individually is 0, 1, 2, 3, or 4;

R Q is selected from the group consisting of:

alkyl,

cycloalkyl,

phenyl,

benzyl,

tetrahydrofuranyl,

tetrahydropyranyl,

pyrrolidinyl,

piperidinyl, and

—OR 8 , wherein

the cycloalkyl is optionally substituted with one or more R c ;

the phenyl and benzyl are each independently optionally substituted with one or more R a ; and

the tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl and piperidinyl are each independently optionally substituted with one or more R hc ;

each of R S and R V is independently selected from the group consisting of alkyl;

alkenyl;

alkynyl;

aryl;

aryl substituted with one or more R a ;

azido;

cyano;

cycloalkyl;

cycloalkyl substituted with one or more R c ;

fused cycloalkylaryl substituted with one or more R f1 ;

fused arylcycloalkyl substituted with one or more R f2 ;

fused heterocyclyaryl substituted with one or more R f3 ;

fused arylheterocyclyl substituted with one or more R f4 ;

fused cycloalkylheteroaryl substituted with one or more R f5 ;

fused heteroarylcycloalkyl substituted with one or more R f6 ;

fused heterocyclylheteroaryl substituted with one or more R f7 ;

halogen;

haloalkyl;

heterocyclyl;

heterocyclyl substituted with one or more R hc

heteroaryl;

heteroaryl substituted with one or more R ha ;

hydrogen;

—NR 3 R 4 ;

—C(O)NR 3 R 4 ;

—C(O)R 5 ;

—C(O) 2 R 6 ;

—S(O) j R 7 ;

—OR 8 ; and

nitro;

wherein

each of R 3 and R 4 is independently selected from the group consisting of H, acyl, alkyl, alkoxy, alkoxyalkyl, alkylsulfonyl, aryl, cycloalkyl, heterocyclyl and heteroaryl;

j is 0, 1, or 2;

each R 5 , R 6 , R 7 , and R 8 is independently selected from the group consisting of

hydrogen;

alkyl;

alkenyl;

alkynyl;

alkoxy;

aryl;

aryl substituted with one or more R a ;

cycloalkyl;

cycloalkyl substituted with one or more R c ;

halogen;

haloalkyl;

heterocyclyl;

heterocyclyl substituted with one or more R hc

heteroaryl; and

heteroaryl substituted with one or more R ha ;

wherein each of R a , R c , R f1 % R f2 , R f3 , R f4 , R f5 , R f6 , R f7 , R hc and R ha is independently selected from the group consisting of acyl, alkyl, alkenyl, alkynyl, alkoxy, amide, amino, aryl, cyano, cycloalkyl, halogen, haloalkyl, haloalkoxy, heteroaryl, hydroxy, nitro, —C(O)OR 9 , —SO 2 R 10 , —SR 11 , —C(O)R 12 , —C(O)NR 13 , —NH—SO 2 —R 14 , —SO 2 —NR 15 R 16 , and —SO 2 —CH 2 —SO 2 —CH 3 ; and wherein

each of R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , and R 16 , is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl, and heteroaryl.

15. A compound, where the compound is a compound selected from the group consisting of:

1-cyclopentyl-7-methoxy-3-thiophen-2-yl-1H-pyrimido[5,4-c]quinoline-2,4-dione;

1-cyclopentyl-7-methoxy-3-phenyl-1H-pyrimido[5,4-c]quinoline-2,4-dione;

1-cyclopentyl-7-methoxy-3-thiophen-3-yl-1H-pyrimido[5,4-c]quinoline-2,4-dione;

1-cyclopentyl-7-methoxy-3-(4-methyl-thiophen-2-yl)-1H-pyrimido[5,4-c]quinoline-2,4-dione;

1-cyclopentyl-7-methoxy-3-m-tolyl-1H-pyrimido[5,4-c]quinoline-2,4-dione;

1-cyclopentyl-7-methoxy-3-p-tolyl-1H-pyrimido[5,4-c]quinoline-2,4-dione;

1-cyclopentyl-3-(4-fluoro-3-methyl-phenyl)-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione;

1-cyclopentyl-3-(3-fluoro-4-methyl-phenyl)-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione;

1-cyclopentyl-3-(3-fluoro-phenyl)-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione;

1-cyclopentyl-7-methoxy-3-(5-methyl-2-trifluoromethyl-furan-3-yl)-1H-pyrimido[5,4-c]-quinoline-2,4-dione;

3-(3-chloro-phenyl)-1-cyclopentyl-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione;

1-cyclopentyl-3-(3,5-dimethyl-phenyl)-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione;

1-cyclopentyl-3-(3-ethyl-phenyl)-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione;

1-cyclopentyl-3-(2,3-dimethyl-phenyl)-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione;

1-cyclopentyl-3-(2,5-dimethyl-phenyl)-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione;

1-cyclopentyl-3-(3,4-dimethyl-phenyl)-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione;

1-cyclopentyl-7-methoxy-3-o-tolyl-1H-pyrimido[5,4-c]quinoline-2,4-dione;

4-[3-(3-chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester;

3-(3-chloro-phenyl)-7-methoxy-1-piperidin-4-yl-1H-pyrimido[5,4-c]quinoline-2,4-dione;

3-(3-chloro-phenyl)-1-(1-methanesulfonyl-piperidin-4-yl)-7-methoxy-1H-pyrimido[5,4-c]-quinoline-2,4-dione;

3-(3-chloro-phenyl)-7-methoxy-1-[1-(propane-2-sulfonyl)-piperidin-4-yl]-1H-pyrimido[5,4-c]-quinoline-2,4-dione;

4-[3-(3-chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-1-yl]-piperidine-1-carboxylic acid isopropyl ester;

trans-4-[3-(3-Chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-1-yl]-cyclohexane-carboxylic acid ethyl ester;

trans-4-[3-(3-Chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-1-yl]-cyclohexanecarboxylic acid;

cis-4-[3-(3-Chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-1-yl]-cyclohexane-carboxylic acid ethyl ester;

cis-4-[3-(3-Chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-1-yl]-cyclohexane-carboxylic acid;

3-(3-chloro-phenyl)-1-cyclohexyl-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione;

3-[(R)-3-(3-chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-1-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester;

(R)-3-(3-chloro-phenyl)-7-methoxy-1-pyrrolidin-3-yl-1H-pyrimido[5,4-c]quinoline-2,4-dione;

3-(3-chloro-phenyl)-1-((R)-1-methanesulfonyl-pyrrolidin-3-yl)-7-methoxy-1H-pyrimido[5,4-c]-quinoline-2,4-dione;

3-[(S)-3-(3-chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-1-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester;

(S)-3-(3-chloro-phenyl)-7-methoxy-1-pyrrolidin-3-yl-1H-pyrimido[5,4-c]quinoline-2,4-dione;

3-(3-chloro-phenyl)-1-((S)-1-methanesulfonyl-pyrrolidin-3-yl)-7-methoxy-1H-pyrimido[5,4-c]-quinoline-2,4-dione;

3-(3-chloro-phenyl)-1-(1-ethanesulfonyl-piperidin-4-yl)-7-methoxy-1H-pyrimido[5,4-c]-quinoline-2,4-dione;

4-[3-(3-chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-1-yl]-piperidine-1-carboxylic acid methyl ester;

3-(3-chloro-phenyl)-1-(1-methanesulfonyl-piperidin-4-yl)-7-methoxy-1H-pyrimido[5,4-c]-quinoline-2,4-dione; and

N-{4-[(S)-3-(3-chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-1-yl]-trans-cyclohexyl}-methanesulfonamide;

or a pharmaceutically acceptable salt thereof.

16. 1-Cyclopentyl-7-methoxy-3-(4-methyl-thiophen-2-yl)-1H-pyrimido[5,4-c]quinoline-2,4-dione or a pharmaceutically acceptable salt thereof.

17. The compound according to claim 16 , where the compound is 1-cyclopentyl-7-methoxy-3-(4-methyl-thiophen-2-yl)-1H-pyrimido[5,4-c]quinoline-2,4-dione.

18. 1-Cyclopentyl-7-methoxy-3-m-tolyl-1H-pyrimido[5,4-c]quinoline-2,4-dione or a pharmaceutically acceptable salt thereof.

19. The compound according to claim 18 , where the compound is 1-cyclopentyl-7-methoxy-3-m-tolyl-1H-pyrimido[5,4-c]quinoline-2,4-dione.

20. 3-(3-Chloro-phenyl)-1-(1-methane-sulfonyl-piperidin-4-yl)-7-methoxy-1H-pyrimido[5,4-c]-quinoline-2,4-dione or a pharmaceutically acceptable salt thereof.

21. The compound according to claim 20 , where the compound is 3-(3-chloro-phenyl)-1-(1-methane-sulfonyl-piperidin-4-yl)-7-methoxy-1H-pyrimido[5,4-c]-quinoline-2,4-dione.

22. Trans-4-[3-(3-chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido-[5,4-c]quinolin-1-yl]-cyclohexanecarboxylic acid or a pharmaceutically acceptable salt thereof.

23. The compound according to claim 22 , where the compound is trans-4-[3-(3-chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-1-yl]-cyclohexane-carboxylic acid.

24. 3-(3-Chloro-phenyl)-1-((R)-1-methane-sulfonyl-pyrrolidin-3-yl)-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione or a pharmaceutically acceptable salt thereof.

25. The compound according to claim 24 , where the compound is 3-(3-chloro-phenyl)-1-((R)-1-methane-sulfonyl-pyrrolidin-3-yl)-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione.

26. 3-(3-Chloro-phenyl)-1-((S)-1-methane-sulfonyl-pyrrolidin-3-yl)-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione or a pharmaceutically acceptable salt thereof.

27. The compound according to claim 26 , where the compound is 3-(3-chloro-phenyl)-1-((S)-1-methane-sulfonyl-pyrrolidin-3-yl)-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione.

28. 3-(3-Chloro-phenyl)-1-(1-ethanesulfonyl-piperidin-4-yl)-7-methoxy-1H-pyrimido-[5,4-c]quinoline-2,4-dione or a pharmaceutically acceptable salt thereof.

29. The compound according to claim 28 , where the compound is 3-(3-chloro-phenyl)-1-(1-ethanesulfonyl-piperidin-4-yl)-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione.

30. N-{4-[(S)-3-(3-Chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-1-yl]-trans-cyclohexyl}-methanesulfonamide or a pharmaceutically acceptable salt thereof.

31. The compound according to claim 30 , where the compound is N-{4-[(S)-3-(3-chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-1-yl]-trans-cyclohexyl}-methanesulfonamide.

32. A pharmaceutical composition comprising a compound according to claim 15 and a pharmaceutically acceptable carrier, diluent, or excipient.

33. A pharmaceutical composition comprising a compound according to claim 16 and a pharmaceutically acceptable carrier, diluent, or excipient.

34. A pharmaceutical composition comprising a compound according to claim 17 and a pharmaceutically acceptable carrier, diluent, or excipient.

35. A pharmaceutical composition comprising a compound according to claim 18 and a pharmaceutically acceptable carrier, diluent, or excipient.

36. A pharmaceutical composition comprising a compound according to claim 19 and a pharmaceutically acceptable carrier, diluent, or excipient.

37. A pharmaceutical composition comprising a compound according to claim 20 and a pharmaceutically acceptable carrier, diluent, or excipient.

38. A pharmaceutical composition comprising a compound according to claim 21 and a pharmaceutically acceptable carrier, diluent, or excipient.

39. A pharmaceutical composition comprising a compound according to claim 22 and a pharmaceutically acceptable carrier, diluent, or excipient.

40. A pharmaceutical composition comprising a compound according to claim 23 and a pharmaceutically acceptable carrier, diluent, or excipient.

41. A pharmaceutical composition comprising a compound according to claim 24 and a pharmaceutically acceptable carrier, diluent, or excipient.

42. A pharmaceutical composition comprising a compound according to claim 25 and a pharmaceutically acceptable carrier, diluent, or excipient.

43. A pharmaceutical composition comprising a compound according to claim 26 and a pharmaceutically acceptable carrier, diluent, or excipient.

44. A pharmaceutical composition comprising a compound according to claim 27 and a pharmaceutically acceptable carrier, diluent, or excipient.

45. A pharmaceutical composition comprising a compound according to claim 28 and a pharmaceutically acceptable carrier, diluent, or excipient.

46. A pharmaceutical composition comprising a compound according to claim 29 and a pharmaceutically acceptable carrier, diluent, or excipient.

47. A pharmaceutical composition comprising a compound according to claim 30 and a pharmaceutically acceptable carrier, diluent, or excipient.

48. A pharmaceutical composition comprising a compound according to claim 31 and a pharmaceutically acceptable carrier, diluent, or excipient.

Assignments (11)