Monocyclic cyanoenones and methods of use thereof

1. A compound of the formula:

wherein:

R 1 , R 3 , R 4 , R 5 and R 6 are each independently:

hydrogen, hydroxy, amino, cyano, or

alkyl (C≦18) , alkenyl (C≦18) , alkynyl (C≦18) ; aryl (C≦18) , aralkyl (C≦18) , heteroaryl (C≦18) , heteroaralkyl (C≦18) , acyl (C≦18) , alkoxy (C≦18) , alkenyloxy (C≦18) , alkynyloxy (C≦18) , aryloxy (C≦18) , aralkoxy (C≦18) , heteroaryloxy (C≦18) , heteroaralkoxy (C≦18) , acyloxy (C≦18) , alkyl-amino (C≦18) , dialkylamino (C≦18) , alkoxyamino (C≦18) , alkenyl-amino (C≦18) , alkynylamino (C≦18) , arylamino (C≦18) , aralkylamino (C≦18) , heteroarylamino (C≦18) , heteroaralkylamino (C≦18) , alkylsulfonylamino (C≦18) , amido (C≦18) , alkylideneamino (C≦18) ; aralkylideneamino (C≦18) ; or a substituted version of any of these groups;

R 1 and R 3 are taken together and are alkanediyl (C≦18) , alkenediyl (C≦18) , arenediyl (C≦18) , alkoxydiyl (C≦18) , alkenyloxydiyl (C≦18) , alkylaminodiyl (C≦18) , alkenylaminodiyl (C≦18) , alkenylaminooxydiyl (C≦18) , alkenyl-aminothiodiyl (C≦18) , with R 2 , R 4 , R 5 and R 6 as defined above; or

R 3 and R 5 are taken together and are alkanediyl (C≦18) , alkenediyl (C≦18) , arenediyl (C≦18) , alkoxydiyl (C≦18) , alkenyloxydiyl (C≦18) , alkylaminodiyl (C≦18) , alkenylaminodiyl (C≦18) , alkenylaminooxydiyl (C≦18) , alkenyl-aminothiodiyl (C≦18) , with R 1 , R 2 , R 4 and R 6 as defined above;

provided that: R 4 is absent when the atom to which it is bound forms part of a double bond; R 6 is absent when the atom to which it is bound forms part of a double bond; neither R 1 nor R 2 is hydrogen; and R 1 and R 2 are not both methyl; and

R 2 is cyano, alkynyl (C≦8) , substituted alkynyl (C≦8) , or —C≡C—R 9 wherein R 9 is:

hydrogen or cyano; or

alkyl (C≦6) , aryl (C≦6) , acyl (C≦6) , alkylsilyl (C≦6) or a substituted version of any of these groups;

or a pharmaceutically acceptable salt or tautomer of the formula.

2. The compound of claim 1 further defined as:

wherein:

R 1 is:

hydroxy, amino, cyano, or

alkyl (C≦18) , alkenyl (C≦18) , alkynyl (C≦18) , aryl (C≦18) , aralkyl (C≦18) , heteroaryl (C≦18) , heteroaralkyl (C≦18) , acyl (c≦18) , alkoxy (C≦18) , alkenyloxy (C≦18) , alkynyloxy (C≦18) , aryloxy (C≦18) , aralkoxy (C≦18) , heteroaryloxy (C≦18) , heteroaralkoxy (C≦18) , acyloxy (C≦18) , alkyl-amino (C≦18) , dialkylamino (C≦18) , alkoxyamino (C≦18) , alkenyl-amino (C≦18) , alkynylamino (C≦18) , arylamino (C≦18) , aralkylamino (C≦18) , heteroarylamino (C≦18) , heteroaralkylamino (C≦18) , alkylsulfonylamino (C≦18) , amido (C≦18) , alkylideneamino (C≦18) , aralkylideneamino (C≦18) , or a substituted version of any of these groups, provided that R 1 and R 2 are not both methyl; and

R 2 is cyano, alkynyl (C≦8) , substituted alkynyl (C≦8) , or —C≡C—R 9 wherein R 9 is:

hydrogen or cyano; or

alky (C≦6) , aryl (C≦6) alkylsilyl (C≦6) or a substituted version of any of these groups;

or a pharmaceutically acceptable salt or tautomer of the formula.

3. The compound of claim 2 , wherein the bond between atoms 4 and 5 is a double bond.

4. The compound of claim 3 , wherein R 2 is alkynyl (C≦8) or substituted alkynyl (C≦8) .

5. The compound of claim 3 , wherein R 2 is —C≡C—R 9 , wherein R 9 is:

hydrogen or cyano; or

alkyl (C≦6) , aryl (C≦6) , acyl (C≦6) , alkylsilyl (C≦6) or a substituted version of any of these groups.

6. The compound of claim 5 , wherein R 9 is hydrogen.

7. The compound of claim 5 , wherein R 9 is —Si(CH 3 ) 2 C(CH 3 ) 3 .

8. The compound of claim 1 , wherein R 2 is cyano.

9. The compound of claim 3 , wherein R 1 is alkyl (C≦8) or substituted alkyl (C≦8) .

10. The compound of claim 9 , wherein R 1 is methyl or ethyl.

11. The compound of claim 3 , wherein R 1 is aralkyl (C≦18) , substituted aralkyl (C≦18) , heteroaralkyl (C≦18) or substituted heteroaralkyl (C≦18) .

12. The compound of claim 3 , wherein R 1 is cyano.

13. The compound according to claim 1 , further defined as:

wherein R 1 is:

cyano, or

alkyl (C≦18) , alkenyl (C≦18) , alkynyl (C≦18) , aryl (C≦18) , aralkyl (C≦18) , heteroaryl (C≦18) , heteroaralkyl (C≦18) , acyl (C≦18) , alkoxy (C≦18) , alkenyloxy (C≦18) , alkynyloxy (C≦18) , aryloxy (C≦18) , aralkoxy (C≦18) , heteroaryloxy (C≦18) , heteroaralkoxy (C≦18) , acyloxy (C≦18) , alkylamino (C≦18) , dialkylamino (C≦18) , alkoxyamino (C≦18) , alkenylamino (C≦18) , alkynylamino (C≦18) , arylamino (C≦18) , aralkylamino (C≦18) , heteroarylamino (C≦18) , heteroaralkylamino (C≦18) , alkylsulfonylamino (C≦18) , amido (C≦18) , alkylideneamino (C≦18) , aralkylideneamino (C≦18) , or a substituted version of any of these groups;

or a pharmaceutically acceptable salt or tautomer of the formula.

14. The compound of claim 1 , wherein R 5 is hydrogen.

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

16. A pharmaceutical composition comprising as an active ingredient a compound of claim 1 and a pharmaceutically acceptable carrier.