Oxamide IMPDH inhibitors

1. The compound of the formula

wherein

R 2 is hydrogen, unsubstituted lower alkyl, lower alkoxy, halo, hydroxy or cyano;

R 3 is hydrogen, unsubstituted lower alkyl, lower alkoxy, halo, or cyano;

R 5 is hydrogen, unsubstituted lower alkyl, lower alkoxy, halo, or cyano;

R 6 is hydrogen, unsubstituted lower alkyl, lower alkoxy, halo, or cyano;

R 7 is hydrogen, or unsubstituted lower alkyl;

R 9 is hydrogen, lower alkyl, or aryl-lower alkyl; and

R 10 is hydrogen

R 11 is H or lower alkyl, R 13 is H or unsubstituted lower alkyl,

n=0 or 1,

R a , R b are lower alkyl or R a and R b taken together with the carbon atom to which they are attached form a 3 to 7 member carbocycle, and

R 12 is heterocyclyl, aryl or lower cycloalkyl and Z is O, S or NR 28 ,

wherein R 28 is H or lower alkyl.

2. The compound of claim 1 of the formula

wherein

R 11 is H or lower alkyl, R 13 is H or unsubstituted lower alkyl,

n=0 or 1 and

R 12 is heterocyclyl, aryl or lower cycloalkyl.

3. The compound of claim 2 wherein

R 2 is methoxy and R 3 , R 5 , R 6 , R 9 , R 10 , R 11 and R 13 are hydrogen.

4. The compound of claim 3 wherein R 12 is aryl, a 3 to 7 membered cycloalkyl ring, or a 5 or 6-membered monocyclic or 9 or 10-membered bicyclic saturated or unsaturated heterocyclic ring with 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulfur.

5. The compound of claim 4 selected from the group consisting of:

Name

Structure

N-[3-(4-Hydroxy-phenoxy)-1,1- dimethyl-propyl]-N′-(3-methoxy-4- oxazol-5-yl-phenyl)-oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[3-(4- methoxyphenoxy)-1,1- dimethylpropyl]oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-(4- nitrophenoxy)propyl]oxalamide

N-[3-(2-Hydroxyphenoxy)-1,1- dimethylpropyl]-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

N-[3-(4-Amino-phenoxy)-1,1- dimethyl-propyl]-N′-(3-methoxy-4- oxazol-5-yl-phenyl)-oxalamide

N-[3-(-Acetylamino-phenoxy)- 1,1-dimethyl-propyl]-N′-(3- methoxy-4-oxazol-5-yl-phenyl)- oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-(3- pyridyloxy)propyl]oxalamide

N-[3-(3-Hydroxyphenoxy)-1,1- dimethylpropyl]-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[3-(3- methoxyphenoxy)-1,1- dimethylpropyl]oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-(3- nitrophenoxy)propyl]oxalamide

N-[3-(3-Aminophenoxy)-1,1- dimethylpropyl)-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

4-[3-[[[3-Methoxy-4-(5-oxazolyl) anilio]oxalyl]amino]-3- methylbutoxy]benzoic acid

2-[3-[[[3-Methoxy-4-(5-oxazolyl) anilino]oxalyl]amino]-3- methylbutoxy]benzoic acid

3-[3-[[[3-Methoxy-4-(5-oxazolyl) anilino]oxalyl]amino]-3- methylbutoxy]benzoic acid

2-[4-[3-[[[3-Methoxy-4-(5- oxazolyl)anilino]oxalyl]anino]-3- methylbutoxy]phenoxy]acetic acid

2-[2-[3-[[[3-Methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-3- methylbutoxy]phenoxy]acetic acid

N-[3-Methoxy-4-(5- oxazolyl)phenyl]-N′-(1,1-dimethyl- 3-phenoxypropyl)oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-(1- oxido-3-pyridyloxy)propyl] oxalamide

N-[3-(3,4-Dihydroxyphenoxy)-1,1- dimethylpropyl]-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-[4- (methylcarbamoyl)phenoxy]propyl] oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[3-(3,4- dimethoxyphenoxy)-1,1- dimethylpropyl]oxalamide

N-[3-[4-[(2-Hydroxyethyl) carbamoyl]phenoxy]-1,1-dimethyl- propyl]-N′-[3-methoxy-4-(5- oxazolyl)phenyl]oxalamide

N-[3-(3-Chlorophenoxy)-1,1- dimethylpropyl]-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-(3- pyridyloxy)propyl]oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-(2- pyridyloxy)propyl]oxalamide

2-[4-[3-[[[3-Methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-3- methylbutoxy]phenyl]acetic acid

2-[3-[3-[[[3-Methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-3- methylbutoxy]phenyl]acetic acid

4-[2-[[[3-Methoxy-4-(5-oxazolyl) anilino]oxalyl]amino]-2- methylpropoxy]benzoic acid

4-[3-[[[3-Methoxy-4-(5-oxazolyl) anilino]oxalyl]amino]-3- methylbutoxy]-2-methylbenzoic acid

3-[3-[3-[[[3-Methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-3- methylbutoxy]phenyl]propionic acid

3-[4-[3-[[[3-Methoxy-4- (5oxazolyl)anilino]oxalyl]amino]- 3-methylbutoxy]phenyl]propionic acid

3-[2-[3-[[[3-Methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-3- methylbutoxy]phenyl]propionic acid

2-[3-[3-[[[3-Methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-3- 3-methylbutoxy]phenoxy]acetic acid

4-[3-[[[3-Methoxy-4-(5-oxazolyl) anilino]oxalyl-amino]-3- methylbutoxy]-3-methylbenzoic acid

N-[3-(4-Cyano-2- methoxyphenoxy)-1,1- dimethylpropyl]-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

N-[3-(3-Cyanophenoxy-1,1- dimethylpropyl]-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

N-[3-[4-(4-Acetyl-1-piperazinyl) phenoxy]-1,1-dimethylpropyl]-N′- [3-methoxy-4-(5-oxazolyl)phenyl] oxalamide

N-[3-Methoxy-4-(5- oxazolyl)phenyl]-N′-[1,1-dimethyl- 3-(2-morpholinophenoxy)propyl] oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-[3- (dimethylamino)phenoxy] propyl]oxalamide

N-[3-(1,3-Benzodioxol-5-yloxy)- 1,1-dimethylpropyl]-N′-[3- methoxy-4-(5-oxazolyl)phenyl] oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[3-(3,4,5- trimethoxyphenoxy)-1,1- dimethylpropyl]oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[3-(3,5- dimethoxyphenoxy)-1,1- dimethylpropyl]oxalamide

N-[3-(5,6,7,8-Tetrahydro-5-oxo-2- naphthyloxy)-1,1-dimethylpropyl]- N′-(3-methoxy-4-(5- oxazolyl)phenyl]oxalamide

N-[3-(2-Acetamido-5- methylphenoxy)-1,1- dimethylpropyl]-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

N-[3-(3-Acetamidophenoxy)-1,1- dimethylpropyl]-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

N-[3-(1H-Indol-4-yloxy)-1,1- dimethylpropyl]-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

N-[3-(2-Fluoro-6- methoxyphenoxy)-1,1- dimethylpropyl]-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-2-oxo- 2H-1-benzopyran-7- yloxy)propyl]oxalamide

N-[3-(4-Acetyl-3-methylphenoxy)- 1,1-dimethylpropyl]-N′-[3- methoxy-4-(5-oxazolyl)phenyl] oxalamide

(E)-N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-[4-(3- oxo-1-butenyl)phenoxy]propyl] oxalamide

N-[3-(3-Acetylphenoxy)-1,1- dimethylpropyl]-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

N-[3-(4-Acetylphenoxy)-1,1- dimethylpropyl]-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

N-[3-(4-Acetamido-2- chlorophenoxy)-1,1- dimethylpropyl]-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

N-[3-Methoxy-4-(5- oxazolyl)phenyl]-N′-[1,1-dimethyl- 3-(4-pyridyloxy)propyl]oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-(1- oxido-4-pyridyloxy)propyl] oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-(2,6- dimethyl-4-pyridyloxy)propyl] oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-(2,6- dimethyl-1-oxido-4-pyridyloxy) propyl]oxalamide

N-[2-(4-Cyanophenoxy)-1,1- dimethylethyl)-N′-(3-methoxy-4-(5- oxazolyl)phenyl]oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[3-(2-methoxy-4- pyridyloxy)-1,1-dimethylpropyl] oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-2-[4-(1H- tetrazol-5-yl)phenoxy]ethyl] oxalamide

N-[3-(4-Cyanophenoxy)-1,1- dimethylpropyl]-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

N-[2-(3-Cyanophenoxy)-1,1- dimethylethyl)-N′-[3-methoxy-4-(5- oxazolyl)phenyl]oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-2-[3-(1H- tetrazol-5-yl)phenoxy]ethyl] oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-[4-(1H- tetrazol-5-yl)phenoxy]propyl] oxalamide

Benzyl 2-methoxy-4-[3-[[[3- methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-3- methylbutoxy]benzoate

3-Chloro-4-[3-[[[3-methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-3- methylbutoxy]benzoic acid

2-Methoxy-4-[3-[[[3-methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-3- methylbutoxy]benzoic acid

3-Methoxy-4-[3-[[[3-methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-3- methylbutoxy]benzoic acid

2-Chloro-4-[3-[[[3-methoxy-4-(5- oxazolyl)anilino]oxalyl)amino]-3- methylbutoxy-benzoic acid

4-[3-[[[3-Methoxy-4-(5-oxazolyl) anilino]oxalyl]amino]-3- methylbutoxy]-2- quinolinecarboxylic acid

(cis/trans)-4-[3-[[[3-Methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-3- methylbutoxy]-1- cyclohexanecarboxylic acid

(cis/trans)-4-[2-[[[3-Methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-2- methylpropoxy]-1- cyclohexanecarboxylic acid

3-Fluoro-4-[3-[[[3-methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-3- methylbutoxy)benzoic acid

3-Acetamido-4-[3-[[[3-methoxy-4- (5-oxazolyl)anilino)oxalyl]amino]- 3-methylbutoxy]benzoic acid

3-(Methanesulfonamido)-4-[3-[[[3- methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-3- methylbutoxy]benzoic acid

4-[3-[[[3-Methoxy-4-(5-oxazolyl) anilino]oxalyl]amino]-3- methylbutoxy]-3,5-dimethylbenzoic acid

3-[3-[[[3 -Methoxy-4-(5-oxazolyl) anilino]oxalyl]amino]-3- methylbutoxy]-2- pyridinecarboxylic acid

8-[3-[[[3-Methoxy-4-(5-oxazolyl) anilino]oxalyl]amino)-3- methylbutoxy]-2- quinolinecarboxylic acid

5-[3-[[[3-Methoxy-4-(5-oxazolyl) anilino)oxalyl]amino]-3- methylbutoxy]-2-indolecarboxylic acid

6. The compound of claim 1 of the formula:

wherein

R 11 is H or lower alkyl, R 13 is H or unsubstituted lower alkyl,

n=0 or 1, m=1 to 5 and,

R 12 is heterocyclyl, aryl or lower cycloalkyl.

7. The compound of 6 wherein

R 2 is methoxy and R 3 , R 5 , R 6 , R 9 , R 10 , R 11 and R 13 are hydrogen.

8. The compound of claim 7 wherein R 12 is aryl, a 3 to 7 membered cycloalkyl ring, or a 5 or 6-membered monocyclic or 9 or 10-membered bicyclic saturated or unsaturated ring with 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulfur.

9. The compound of claim 8 selected from the group consisting of:

4-[2-[1-[[[3-Methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-1- cyclopropyl]ethoxy]benzoic acid

Benzyl 4-[2-[1-[[[3-methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-1- cyclobutyl]ethoxy]benzoate

Benzyl 4-[2-[1-[[[3-methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-1- cyclopentyl]ethoxy]benzoate

Benzyl 4-[2-[1-[[[3-methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-1- cyclohexyl]ethoxy]benzoate

4-[2-[1-[[[3-Methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-1- cyclopentyl]ethoxy]benzoic acid

4-[2-[1-[[[3-Methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-1- cyclohexyl]ethoxy]benzoic acid

and

4-[2-[1-[[[3-Methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-1- cyclobutyl]ethoxy]benzoic acid

10. The compound of claim 1 of the formula

11. The compound of claim 10 wherein

R 2 is methoxy and R 3 , R 5 , R 6 , R 9 , R 10 , R 11 and R 13 are hydrogen.

12. The compound of claim 11 wherein R 12 is aryl, a 3 to 7 membered cycloalkyl ring, or a 5 or 6-membered monocyclic or 9 or 10-membered bicyclic saturated or unsaturated heterocyclic ring with 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulfur.

13. The compound of claim 12 selected from the group consisting of:

Name

Structure

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-2- (phenylthio)ethyl]oxalamide

N-[2-(4-Hydroxyphenylthio)-1,1- dimethylethyl]-N′-[3-methoxy-4-(5- oxazolyl)phenyl]oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-2- (phenylthio)ethyl]oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-2-(2- pyridylthio)ethyl]oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-(2- pyridylthio)propyl]oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-(2- thienylthio)propyl]oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-(2- pyrimidylthio)propyl]oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-(4- pyridylthio)propyl]oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-(2- thiazolylthio)propyl]oxalamide

N-[3-(4-Hydroxyphenylthio)-1,1- dimethylpropyl]-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N′-[1,1-dimethyl-3-(5- methyl-1,3,4-thiadiazol-2-ylthio) propyl]oxalamide

N-[3-(2-Benzooxazolylthio)-1,1- dimethylpropyl]-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

N-[3-(2-Benzothiazolylthio)-1,1- dimethylpropyl]-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

Methyl 4-[2-[[[3-methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-2- methylpropylthio]benzoate

tert-Butyl 6-[3-[[[3-methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-3- methylbutylthio]-3- pyridinecarboxylate

6-[3-[[[3-Methoxy-4-(5-oxazolyl) anilino]oxalyl]amino]-3- methylbutylthio]-3- pyridinecarboxylic acid trifluoroacetate (1:1)

4-[3-[[[3-Methoxy-4-(5-oxazolyl) anilino]oxalyl]amino]-3- methylbutylthio]benzoic acid

N-[2-(4-Benzyloxyphenylthio)-1,1- dimethylethyl]-N′-[3-methoxy-4-(5- oxazolyl)phenyl]oxalamide

N-[2-(4-Benzyloxyphenylthio)-1,1- dimethylpropyl]-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

2-[3-[[[3-Methoxy-4-(5-oxazolyl) anilino]oxalyl]amino]-3- methylbutylthio]-5- benzoxazolecarboxylic acid

N-[3-(1H-Imidazol-2-ylthio)-1,1- dimethylpropyl]-N′-[3-methoxy-4- (5-oxazolyl)phenyl]oxalamide

2-[3-[[[3-Methoxy-4-(5-oxazolyl) anilino]oxalyl]amino]-3- methylbutylthio]-3- pyridinecarboxylic acid trifluoroacetate (1:1)

4-[2-[[[3-methoxy-4-(5- oxazolyl)anilino]oxalyl]amino]-2- methylpropylthio]benzoic acid

and

2-[3-[[[3-Methoxy-4-(5-oxazolyl) anilino]oxalyl]amino]-3- methylbutylthio]-6- benzoxazolecarboxylic acid

14. The compound of claim 1 of the formula

15. Compound of claim 14 , wherein R 2 is methoxy and R 3 , R 5 , R 6 , R 9 , R 10 , R 11 and R 13 are hydrogen and R 28 is hydrogen or methyl.

16. The compound of claim 15 wherein R 12 is aryl.

17. The compound of claim 16 selected from the group consisting of:

Name

Structure

N-[3-Methoxy-4-(5-oxazolyl) phenyl)-N′-[1,1-dimethyl-2-(N methylanilino) ethyl] oxalamide

N-(3-Anilino-1,1-dimethylpropyl)- N′-[3-methoxy-4-(5-oxazolyl) phenyl]oxalamide hydrochloride (1:1)

4-[3-[[[3-Methoxy-4-(5-oxazolyl) anilino]oxalyl]amino]-3- methylbutylamino]benzoic acid