Spiro derivatives as lipoxygenase inhibitors

1. A compound represented by Formula I:

wherein,

X is O or S(O) 0-2 ;

R 1 , R 3 , and R 4 are independently selected from the group consisting of hydrogen, alkyl, halogen amino, and alkenyl, with the proviso that said alkenyl is not substituted with aryl or heteroaryl;

R 2 is hydroxy;

R 5 and R 6 are independently selected from the group consisting of hydrogen, hydroxy, alkoxy, aminosulfonyl, sulfanyl, cyano, —NROR a , or together with the carbon atom to which they are attached, form C═O, or C═NOR a ;

R 7 and R 8 are independently selected from hydrogen, alkyl, alkoxy, and oxazol-2-yl;

R 9 and R 10 together with the carbon atom to which they are attached, form a (C 3 -C 4 )cycloalkyl ring;

R is hydrogen or alkyl;

R a is hydrogen or alkyl;

and n is 1;

with the following proviso no more than one of R 1 , R 3 and R 4 is hydrogen;

or single stereoisomers, mixtures of stereoisomers, or pharmaceutically acceptable salts thereof.

2. A compound of Formula IA:

wherein

X is O or S(O) 0-2 ;

R 41 , R 43 , and R 44 are independently selected from the group consisting of hydrogen, halo, alkenyl, and alkyl optionally substituted with amino, or alkoxy;

R 42 is hydroxy;

R 45 and R 46 are independently selected from the group consisting of hydrogen, hydroxy, alkoxy, aminosulfonyl, sulfanyl, cyano, —NROR a , or together with the carbon atom to which they are attached, form C═O, or C═NOR a ;

R 47 and R 48 are independently selected from hydrogen, alkyl, alkoxy, and oxazol-2-yl;

R 49 and R 410 together with the carbon atom to which they are attached, form a (C 3 -C 4 )cycloalkyl ring;

R a is hydrogen or alkyl;

provided no more than one of R 41 , R 43 and R 44 is hydrogen;

or single stereoisomers, mixtures of stereoisomers, or pharmaceutically acceptable salts thereof.

3. The compound of claim 2 , wherein the compound is of Formula IB:

4. The compound of claim 2 , wherein R 41 , R 43 and R 44 are independently selected from the group consisting of hydrogen, halogen, and alkyl.

5. The compound of claim 2 , wherein R 45 is —NROR a and R 46 is hydrogen.

6. The compound of claim 2 , wherein R 45 is hydroxy and R 46 is hydrogen.

7. The compound of claim 5 , wherein —CR 49 R 410 is cyclobutyl.

8. The compound of claim 6 , wherein —CR 49 R 410 is cyclobutyl.

9. The compound of claim 5 , wherein R 42 is hydroxy and R 41 , R 43 , and R 44 are independently selected from hydrogen, halogen, and C1-C10 alkyl.

10. The compound of claim 6 , R 42 is hydroxy and R 41 , R 43 , and R 44 are independently of selected from hydrogen, halogen and C1-C10 alkyl.

11. The compound of claim 2 , wherein R 45 and R 46 are hydrogen.

12. A compound selected from:

5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

5-chloro-7,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

7-chloro-5,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclopropan]-6-ol;

5-chloro-8-methyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

5,8-dimethyl-7-(3-methylbutyl)-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

8-chloro-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

8-chloro-5-methyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

8-isopropyl-5-methyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

6-hydroxy-7,8-dimethylspiro[chroman-2,1′-cyclopropan]-4(3H)one;

7,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclopropane]-4,6-diol;

7-chloro-5,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-yl (dimethylamino)acetate;

5-isopropyl-8-methyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

6′-hydroxy-5′,7′,8′-trimethylspiro[cyclobutane-1,2′-thiochromen]-4′(3′H)-one;

5′,7′,8′-trimethyl-3′,4′-dihydrospiro[cyclobutane-1,2′-thiochromen]-6′-ol

6′-hydroxy-5′,7′,8′-trimethylspiro[cyclobutane-1,2′-thiochroman]-4′(3′H)-one O-methyloxime;

4′(methoxyamino)-5′,7′,8′-trimethyl-3′,4′-dihydrospiro[cyclobutane-1,2′-thiochromen]-6′-ol;

7-chloro-5,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-yl nicotinate;

5′,7′,8′-trimethyl-3′,4′-dihydrospiro[cyclobutane-1,2′-thiochromen]-6′-yl (dimethylamino)acetate;

5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-yl (dimethylamino)acetate;

5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-yl-2-(4-methylpiperazin-1-yl)acetate;

7,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-yl phenylcarbamate;

5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-yl phenyl(phenylcarbamoyl)carbamate;

2-(7-chloro-5,8-dimethylspiro[chroman-2,1′-cyclobutane]-6-yloxy)-N,N-dimethylethanamine;

4-(methoxyamino)-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-yl acetate;

4-(methoxyamino)-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

2-(dimethylamino)ethyl 5,7,8-trimethylspiro[chroman-2,1′-cyclobutane]-6-yl carbonate;

5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-yl 1H-imidazole-1-carboxylate;

2-(7-chloro-5,8-dimethylspiro[chroman-2,1′-cyclobutane]-6-yloxy)-N,N-dimethylpropan-1-amine;

4-amino-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-yl acetate;

1-(dimethylamino)-3-[(5,7,8-trimethyl-3,4-dihydro-2H-spiro-[chromen-2,1′-cyclobutan]-6-yl)oxy]propan-2-ol;

1-(pyrrolindiny)-3-[(5,7,8-trimethyl-3,4-dihydro-2H-spiro-[chromen-2,1′-cyclobutan]-6-yl)oxy]propan-2-ol;

5,7,8-trimethyl-4-pyrrolidin-1-yl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-(aminomethyl)-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutane]-4,6-diol;

5,7,8-trimethyl-4-morpholin-4-yl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-(1H-imidazol-1-yl)-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutane]-3,6-diol;

3-methoxy-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-(aminomethyl)-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

N-[(6-hydroxy-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl)methyl]acetamide;

4-[(ethylamino)methyl]-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

3-(hydroxymethyl)-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

2-{[(5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-yl)oxy]methyl}pyridine;

2-{[(5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-yl)oxy]methyl}quinoline;

6-hydroxy-3,5,7,8-tetramethylspiro[chroman-2,1′-cyclobutan]-4(3H)-one;

3-(morpholinomethyl)-5,7,8-trimethyl-4-oxo-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-yl acetate;

3-(morpholinomethyl)-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutane]-4,6-diol;

4-[(diethylamino)methyl]-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-methoxy-3,5,7,8-tetramethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

3,5,7,8-tetramethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutane]-4,6-diol;

4-methoxy-3,5,7,8-tetramethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

6-hydroxy-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutane]-4-carbonitrile;

methyl{[(6-hydroxy-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-3-yl)methyl]thio}acetate;

4-ethoxy-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

7,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-methoxy-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-ethoxy-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-(methoxyamino)-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-isopropoxy-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutane]-4,6-diol;

5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutane]-4,6-diol;

8-(hydroxymethyl)-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

8-(methoxymethyl)-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-(cyclopentyloxy)-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutane]-6-diol;

4-(ethoxyamino)-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-(isopropylthio)-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

7,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutane]-4,6-diol;

7,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-yl(dimethylamino)acetate;

4-(methoxyamino)-7,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4′-(ethoxyamino)-5′,7′,8′-trimethyl-3′,4′-dihydrospiro[cyclobutane-1,2′-thiochromen]-6′-ol;

4′-(ethoxyamino)-5′,7′-dimethyl-3′,4′-dihydrospiro[cyclobutan-1,2′-thiochromen]-6′-ol;

4-(ethoxyamino)-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

5-[1-(ethoxyamino)ethyl]-7,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-(methoxyamino)-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-yl acetate;

4′-(methoxyamino)-5′,7′-dimethyl-3′,4′-dihydrospiro[cyclobutane-1,2′-thiochromen]-6′-ol;

4-(ethoxyamino)-7,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-[methoxy(methyl)amino]-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

6-hydroxy-5,7,8-trimethylspiro[chromene-2,1′-cyclobutan]-4(3H)-one oxime;

4-(hydroxyamino)-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

8-[(methoxyamino)methyl]-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol

5,7-dimethyl-8-vinyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-[hydroxy(methyl)amino]-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

6-hydroxy-5,7-dimethylspiro[chromene-2,1′-cyclobutan]-4(3H)-one oxime;

4-(hydroxyamino)-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-[hydroxy(methyl)amino]-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

8-[(ethoxyamino)methyl]-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-[methoxy(methyl)amino]-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-[ethyl(methoxy)amino]-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

5,7-dimethyl-4-methoxyamino-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-yl (dimethylamino)-acetate;

ethyl 4-(methoxyamino)-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-yl carbonate;

6-hydroxy-5,7-dimethylspiro[chromene-2,1′-cyclobutan]-4(3H)-one O-methyloxime;

(4E)-6-hydroxy-5,7-dimethylspiro[chromene-2,1′-cyclobutan]-4(3H)-one O-ethyloxime;

(4Z)-6-hydroxy-5,7-dimethylspiro[chromene-2,1′-cyclobutan]-4(3H)-one O-ethyloxime;

5-ethyl-4-(methoxyamino)-7,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-(ethoxyamino)-5-ethyl-7,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

5-ethyl-6-hydroxy-7,8-dimethylspiro[chromene-2,1′-cyclobutan]-4(3H)-one O-methyloxime;

5-ethyl-6-hydroxy-7,8-dimethylspiro[chromene-2,1′-cyclobutan]-4(3H)-one O-ethyloxime;

6′-hydroxy-5′,7′,8′-trimethylspiro[cyclobutane-1,2′-thiochromen]-4′(3H)-one O-methyloxime;

6′-hydroxy-5′,7′,8′-trimethylspiro[cyclobutane-1,2′-thiochromen]-4′(3′H)-one O-ethyloxime;

6′-hydroxy-5′,7′-dimethylspiro[cyclobutane-1,2′-thiochromen]-4′(3′H)-one O-methyloxime;

3-[(methoxyamino)methyl]-5,7-dimethylspiro[chromene-2,1′-cyclobutan]-6-yl pivalate;

methyl 3-(6-hydroxy-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-8-yl)-4,5-dihydroisoxazole-5-carboxylate;

6′-hydroxy-5′,7′-dimethylspiro[cyclobutane-1,2′-thiochromen]-4′(3′H)-one O-ethyloxime;

5,7-diethyl-6-hydroxyspiro[chromene-2,1′-cyclobutan]-4(3H)-one O-methyloxime;

5,7-diethyl-6-hydroxyspiro[chromene-2,1′-cyclobutan]-4(3H)-one O-ethyloxime;

5,7-diethyl-6-hydroxyspiro[chromene-2,1′-cyclobutan]-4(3H)-one oxime;

(4S)-4-(methoxyamino)-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

(4R)-4-(methoxyamino)-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

5,7-dimethyl-8-(5-butyl-isoxazol-3-yl)-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-(ethoxyamino)-5,7-diethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-(methoxyamino)-5,7-diethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

N-(6-hydroxy-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl)methanesulfonamide;

7-tert-butyl-5-methyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

5,7-dimethyl-8-(1,3-oxazol-5-yl)-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

N-(6-hydroxy-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl)benzenesulfonamide;

5,7-diisopropyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

6-hydroxy-5,7-diisopropyl-3,4-dihydrospiro[chromene-2,1′-yclobutane]-8-carbaldehyde;

4-(methoxyamino)-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-yl isobutyrate;

3-[(ethoxyamino)methyl]-5,7-dimethyl-3,4-dihydrospiro-[chromene-2,1′-cyclobutan]-6-ol;

3-[(methoxyamino)methyl]-5,7-dimethyl-3,4-dihydrospiro-[chromene-2,1′-cyclobutan]-6-ol;

7,8-dimethyl-5-(2-quinolin-2-ylethyl)) 3,4-dihydrospiro-[chromene-2,1′-cyclobutan]-6-ol;

5,7-diisopropyl-8-[(methoxyamino)methyl]3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

5-(3,7-dimethylocta-2,6-dienyl)-7,8-dimethylspiro[chroman-2,1′-cyclobutan]-6-ol;

5,7-diethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

7-isopropyl-4-(methoxyamino)-5-methyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

7-(3,7-dimethylocta-2,6-dienyl)-5,8-dimethylspiro[chroman-2,1′-cyclobutan]-6-ol;

8-(4,5-dimethyl-1H-imidazol-2-yl)-5,7-diethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

7-(4,5-dimethyl-1H-imidazol-2-yl)-5,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

7-ethyl-4-(methoxyamino)-5-methyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

5-ethyl-4-(methoxyamino)-7-methyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

(Z)-5,7-diethyl-8-(hydroxymethyl)-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

5,7-diethyl-8-(hydroxymethyl)-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

7-isopropyl-5-methyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

7-(3,7-dimethyloctyl)-5,8-dimethylspiro[chroman-2,1′-cyclobutan]-6-ol;

8-(hydroxymethyl)-7-isopropyl-5-methylspiro[chroman-2,1′-cyclobutan]-6-ol;

5,7-dimethyl-3-(oxazol-5-yl)spiro[chroman-2,1′-cyclobutan]-6-ol;

7-isopropyl-5-methylspiro[chroman-2,1′-cyclobutane]-4,6-diol;

7-isopropyl-4-methoxy-5-methylspiro[chroman-2,1′-cyclobutan]-6-ol;

7-(5,6-dimethyl-1H-benzo[d]imidazol-2-yl)-5,8-dimethylspiro[chroman-2,1′-cyclobutan]-6-ol;

7-tert-butyl-5-(morpholinomethyl)spiro[chroman-2,1′-cyclobutan]-6-ol;

8-(hydroxymethyl)-5,7-diisopropylspiro[chroman-2,1′-cyclobutan]-6-ol;

8-((hydroxyamino)methyl)-5,7-diisopropylspiro[chroman-2,1′-cyclobutan]-6-ol;

5,8-dimethyl-7-(2-(quinolin-2-yl)ethyl)spiro[chroman-2,1′-cyclobutan]-6-ol;

N-((6-hydroxy-5,7-diisopropylspiro[chroman-2,1′-cyclobutane]-8-yl)methyl)-N-methylacetamide;

5,7-diisopropyl-8-(methoxymethyl)spiro[chroman-2,1′-cyclobutan]-6-ol;

5,7-diethyl-3-(hydroxymethyl)spiro[chroman-2,1′-cyclobutan]-6-ol;

8-(acetamidomethyl)-5,7-diisopropylspiro[chroman-2,1′-cyclobutan]-6-ol;

methyl 2-((5,7-diethyl-6-hydroxyspiro[chroman-2,1′-cyclobutane]-3-yl)methylthio)acetate;

(5,7-diethyl-6-hydroxyspiro[chroman-2,1′-cyclobutane]-3-yl)methyl carbamates;

7-tert-butyl-5-methylspiro[chroman-2,1′-cyclobutane]-4,6-diol;

7-tert-butyl-4-hydroxy-5-methylspiro[chroman-2,1′-cyclobutane]-6-yl acetate;

5,7-diisopropylspiro[chroman-2,1′-cyclobutane]-6-yl 2-amino-2-oxoacetate;

2-hydroxy-2-(6-hydroxy-5,7-diisopropylspiro[chroman-2,1′-cyclobutane]-8-yl)acetonitrile;

5-ethyl-7-isopropylspiro[chroman-2,1′-cyclobutane]-4,6-diol;

(S)-5,7-diethylspiro[chroman-2,1′-cyclobutane]-4,6-diol;

(R)-5,7-diethylspiro[chroman-2,1′-cyclobutane]-4,6-diol;

(S)-7-isopropyl-5-methylspiro[chroman-2,1′-cyclobutane]-4,6-diol;

(R)-7-isopropyl-5-methylspiro[chroman-2,1′-cyclobutane]-4,6-diol;

and single stereoisomers, mixtures of stereoisomers, or pharmaceutically acceptable salts thereof.

13. A compound selected from:

N-(6-hydroxy-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl)acetamide;

N-(6-hydroxy-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl)acetamide;

N-(6-hydroxy-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl)butanamide;

and single stereoisomers, mixtures of stereoisomers, or pharmaceutically acceptable salts thereof.

14. A compound selected from:

4′(methoxyamino)-5′,7′,8′-trimethyl-3′,4′-dihydrospiro[cyclobutane-1,2′-thiochromen]-6′-ol;

4-(methoxyamino)-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-(ethoxyamino)-5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4′-(ethoxyamino)-5′,7′,8′-trimethyl-3′,4′-dihydrospiro[cyclobutane-1,2′-thiochromen]-6′-ol;

4′-(ethoxyamino)-5′,7′-dimethyl-3′,4′-dihydrospiro[cyclobutane-1,2′-thiochromen]-6′-ol;

4-(ethoxyamino)-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4′-(methoxyamino)-5′,7′-dimethyl-3′,4′-dihydrospiro[cyclobutane-1,2′-thiochromen]-6′-ol;

4-[ethyl(methoxy)amino]-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

5-ethyl-4-(methoxyamino)-7,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-(ethoxyamino)-5-ethyl-7,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

(4S)-4-(methoxyamino)-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

(4R)-4-(methoxyamino)-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

4-(methoxyamino)-5,7-diethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

3-[(methoxyamino)methyl]-5,7-dimethyl-3,4-dihydrospiro-[chromene-2,1′-cyclobutan]-6-ol;

7-isopropyl-4-(methoxyamino)-5-methyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

7-ethyl-4-(methoxyamino)-5-methyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

5-ethyl-4-(methoxyamino)-7-methyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

and single stereolsomers, mixtures of stereolsomers, or pharmaceutically acceptable salts thereof.

15. A compound selected from: 5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutane]-4,6-diol;

5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutane]-4,6-diol;

5,7-diethyl-8-(hydroxymethyl)-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

7-isopropyl-5-methylspiro[chroman-2,1′-cyclobutane]-4,6-diol;

7-tert-butyl-5-methylspiro[chroman-2,1′-cyclobutane]-4,6-diol;

5-ethyl-7-isopropylspiro[chroman-2,1′-cyclobutane]-4,6-diol;

(S)-5,7-diethylspiro[chroman-2,1′-cyclobutane]-4,6-diol;

(R)-5,7-diethylspiro[chroman-2,1′-cyclobutane]-4,6-diol;

(S)-7-isopropyl-5-methylspiro[chroman-2,1′-cyclobutane]-4,6-diol;

(R)-7-isopropyl-5-methylspiro[chroman-2,1′-cyclobutane]-4,6-diol;

and single stereoisomers, mixtures of stereoisomers, or pharmaceutically acceptable salts thereof.

16. A compound selected from:

7-isopropyl-5-methyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

5,7-diethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

7-tert-butyl-5-methyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

5,7-dimethyl-8-vinyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

7,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

8-chloro-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol;

5,7-dimethyl-3,4-dihydrospiro[chromene-2,1-cyclobutan]-6-ol;

5,7,8-trimethyl-3,4-dihydrospiro[chromene-2,1′-cyclopropan]-6-ol;

and single stereoisomers, mixtures of stereoisomers, or pharmaceutically acceptable salts thereof.

17. A pharmaceutical composition comprising a compound of claim 1 admixed with a pharmaceutically acceptable excipient.

18. A pharmaceutical composition comprising a compound of claim 12 admixed with a pharmaceutically acceptable excipient.

19. A method of treating a subject suffering from rheumatoid arthritis or atherosclerosis comprising administering to said subject a therapeutically effective amount of a compound of claim 1 .

20. A compound represented by Formula II:

wherein,

X is O or S(O) 0-2 ;

R 21 , R 23 , and R 24 are independently selected from hydrogen or alkyl;

R 22 is hydroxy;

R 26 and R 27 are independently selected from: hydrogen, alkyl, alkoxy, cyano, —CN═N—OR 20 , NR 20 OR 2a and -alkylNR 20 OR 2a ;

R 29 and R 210 together with the carbon atom to which they are attached form a (C 3 -C 4 )cycloalkyl ring;

R 20 is hydrogen or alkyl;

R 2a is hydrogen or alkyl;

with the proviso that when R 26 or R 27 is —NHOR 2a , then no more than one of R 21 , R 22 , R 23 and

R 24 is hydrogen;

or single stereoisomers, mixtures of stereoisomers, or pharmaceutically acceptable salts thereof.

21. A compound of Formula IIA:

wherein,

R 51 , R 53 , and R 54 are independently hydrogen or alkyl;

R 56 and R 57 are independently selected from: hydrogen, alkyl, and cyano;

R 59 and R 510 together with the carbon atom to which they are attached form a (C 3 -C 4 )cycloalkyl ring;

or single stereoisomers, mixtures of stereoisomers, or pharmaceutically acceptable salts thereof.

22. The compound of claim 20 , wherein R 27 is —NR 20 OR 2a .

23. The compound of claim 20 , selected from the group consisting of:

5′,7′,8′-trimethylspiro[cyclobutane-1,2′-thiochromen]-6′-ol;

3-(hydroxymethyl)-5,7,8-trimethylspiro[chromene-2,1′-cyclobutan]-6-ol;

4-(aminomethyl)-5,7,8-trimethylspiro[chromene-2,1′-cyclobutan]-6-ol;

N-[(6-hydroxy-5,7,8-trimethylspiro[chromene-2,1′-cyclobutan]-4-yl)methyl]acetamide;

3-(methoxymethyl)-5,7,8-trimethylspiro[chromene-2,1′-cyclobutan]-6-ol;

3,5,7,8-tetramethylspiro[chromene-2,1′-cyclobutan]-6-ol;

6-hydroxy-5,7,8-trimethylspiro[chromene-2,1′-cyclobutane]-4-carbonitrile;

6-hydroxy-5,7-dimethylspiro[chromene-2,1′-cyclobutane]-3-carbaldehyde O-methyloxime;

3-[(methoxyamino)methyl]-5,7-dimethylspiro[chromene-2,1′-cyclobutan]-6-ol;

3-(1-methoxyethyl)-5,7,8-trimethylspiro[chromene-2,1′-cyclobutan]-6-ol;

3-(1-hydroxyethyl)-5,7,8-trimethylspiro[chromene-2,1′-cyclobutan]-6-ol;

5,7-dimethylspiro[chromene-2,1′-cyclobutan]-6-ol;

6-hydroxy-5,7-dimethylspiro[chromene-2,1′-cyclobutane]-3-carbaldehyde O-ethyloxime;

3-[(ethoxyamino)methyl]-5,7-dimethylspiro[chromene-2,1′-cyclobutan]-6-ol;

5,7-dimethyl-3-(1,3-oxazol-5-yl)spiro[chromene-2,1′-cyclobutan]-6-ol;

5,7-dimethyl-3-(-(4,5-dimethyl-1H-imidazol-2-yl)spiro[chromene-2,1′-cyclobutan]-6-ol;

7-isopropyl-5-methylspiro[chromene-2,1′-cyclobutan]-6-ol;

5,7-diethylspiro[chromene-2,1′-cyclobutan]-6-ol;

5,7-diisopropylspiro[chromene-2,1′-cyclobutan]-6-ol

and single stereoisomers, mixtures of stereoisomers, or pharmaceutically acceptable salts thereof.

24. A pharmaceutical composition comprising a compound of claim 20 admixed with a pharmaceutically acceptable excipient.

25. pharmaceutical composition comprising a compound of claim 23 admixed with a pharmaceutically acceptable excipient.

26. A method of treating a subject suffering from a disorder selected from the group consisting of rheumatoid arthritis or atherosclerosis comprising administering to said subject a therapeutically effective amount of a compound of claim 20 .

27. A compound represented by Formula III:

wherein,

R 30 is selected from the group consisting of alkyl, aralkyl, heterocyclyl and aryl;

R 31 , R 33 , and R 34 are independently hydrogen or alkyl;

R 32 is hydroxy or alkoxy;

R 35 , R 36 , R 37 , and R 38 are hydrogen or together with the carbon atom to which they are attached form C═O;

R 39 and R 310 together with the carbon atom to which they are attached form a (C 3 -C 4 )cycloalkyl ring;

m is 1;

with the proviso no more than one of R 31 , R 33 and R 34 is hydrogen;

or single stereoisomers, mixtures of stereoisomers, or pharmaceutically acceptable salts thereof.

28. A compound of Formula IIIA:

R 60 is selected from the group consisting of alkyl, aralkyl, acyl, heterocyclyl and aryl;

R 61 , R 63 , and R 64 are independently selected from the group consisting of hydrogen or alkyl;

R 65 R 66 , R 67 , and R 68 are hydrogen;

R 69 and R 610 together with the carbon atom to which they are attached form a (C 3 -C 4 )cycloalkyl ring;

with the following provisos: no more than one of R 61 , R 63 and R 64 is hydrogen;

or single stereoisomers, mixtures of stereoisomers, or pharmaceutically acceptable salts thereof.

29. The compound of claim 27 , wherein —CR 35 R 36 is C═O.

30. The compound of claim 27 , wherein —CR 37 R 38 is C═O.

31. The compound of claim 27 , wherein R 35 and R 36 are both hydrogen.

32. The compound of claim 27 wherein R 30 is alkyl substituted with an amido, a sulfonylamino or an aminosulfonyl group.

33. The compound of claim 32 , wherein R 30 is —(CH 2 ) 2-6 —NHS(O) 2 -aryl, —(CH 2 ) 2-6 —S(O) 2 NH-aryl, —(CH 2 ) 2-6 —NHC(O)-aryl, or —(CH 2 ) 2-6 —C(O)NH-aryl.

34. The compound of claim 27 , selected from:

1′-(4-chlorobenzyl)-5′,7′-dimethyl-3′,4′-dihydro-1′H-spiro[cyclobutane-1,2′-quinolin]-6′-ol;

1′-(4-hydroxyphenyl)-7′,8′-dimethyl-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-quinolin]-6′-ol;

1′,7′,8′-trimethyl-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-quinolin]-6′-ol;

4-((6′-hydroxy-5′,7′-dimethyl-3′,4′-dihydro-1′H-spiro[cyclobutane-1,2′-quinoline]-1′-yl)methyl)benzoic acid;

methyl 4-((6′-hydroxy-5′,7′-dimethyl-3′,4′-dihydro-1′H-spiro[cyclobutane-1,2′-quinoline]-1′-yl)methyl)benzoate;

5′,7′-dimethyl-1′-(quinolin-2-ylmethyl)-3′,4′-dihydro-1′H-spiro[cyclobutane-1,2′-quinolin]-6′-ol;

and single stereoisomers, mixtures of stereoisomers, or pharmaceutically acceptable salts thereof.

35. A pharmaceutical composition comprising a compound of claim 27 admixed with a pharmaceutically acceptable excipient.

36. A pharmaceutical composition comprising a compound of claim 34 admixed with a pharmaceutically acceptable excipient.

37. A method of treating a mammal suffering from rheumatoid arthritis or atherosclerosis comprising contacting a cell with an effective amount of a compound of claim 27 .