초록 ▼

The present invention is concerned with certain novel spiro substituted heterocylic ring derivatives. These compounds may be useful in the manufacture of pharmaceutical compositions for treating disorders mediated by lipoxygenases. They may also be useful in the manufacture of pharmaceutical formula

The present invention is concerned with certain novel spiro substituted heterocylic ring derivatives. These compounds may be useful in the manufacture of pharmaceutical compositions for treating disorders mediated by lipoxygenases. They may also be useful in the manufacture of pharmaceutical formulations for the treatment of lipoxygenase-mediated disorders.

대표청구항 ▼

What is claimed is: 1. A compound represented by Formula I: wherein, X is O or S(O)0-2; R1, R3, and R4 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; R2 is hydroxy

What is claimed is: 1. A compound represented by Formula I: wherein, X is O or S(O)0-2; R1, R3, and R4 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; R2 is hydroxy; R5 and R6 are independently selected from the group consisting of hydrogen, hydroxy, alkoxy, aminosulfonyl, sulfanyl, cyano,--NRORa, or together with the carbon atom to which they are attached, form C═O, or C═NORa; R7 and R8 are independently selected from hydrogen, alkyl, alkoxy, and oxazol-2-yl; R9 and R10 together with the carbon atom to which they are attached, form a (C3-C4)cycloalkyl ring; R is hydrogen or alkyl; Ra is hydrogen or alkyl; and n is 1; with the following proviso no more than one of R1, R3 and R4 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; R41, R43, and R44 are independently selected from the group consisting of hydrogen, halo, alkenyl, and alkyl optionally substituted with amino, or alkoxy; R42 is hydroxy; R45 and R46 are independently selected from the group consisting of hydrogen, hydroxy, alkoxy, aminosulfonyl, sulfanyl, cyano,--NRORa, or together with the carbon atom to which they are attached, form C═O, or C═NORa; R47 and R48 are independently selected from hydrogen, alkyl, alkoxy, and oxazol-2-yl; R49 and R410 together with the carbon atom to which they are attached, form a (C3-C4)cycloalkyl ring; Ra is hydrogen or alkyl; provided no more than one of R41, R43 and R44 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 R41, R43 and R44 are independently selected from the group consisting of hydrogen, halogen, and alkyl. 5. The compound of claim 2, wherein R45 is--NRORa and R46 is hydrogen. 6. The compound of claim 2, wherein R45 is hydroxy and R46 is hydrogen. 7. The compound of claim 5, wherein--CR49R410 is cyclobutyl. 8. The compound of claim 6, wherein--CR49R410 is cyclobutyl. 9. The compound of claim 5, wherein R42 is hydroxy and R41, R43, and R44 are independently selected from hydrogen, halogen, and C1-C10 alkyl. 10. The compound of claim 6, R42 is hydroxy and R41, R43, and R44 are independently of selected from hydrogen, halogen and C1-C10 alkyl. 11. The compound of claim 2, wherein R45 and R46 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; R21, R23, and R24 are independently selected from hydrogen or alkyl; R22 is hydroxy; R26 and R27 are independently selected from: hydrogen, alkyl, alkoxy, cyano,--CN═N--OR20, NR20OR2a and-alkylNR20OR2a; R29 and R210 together with the carbon atom to which they are attached form a (C3-C4)cycloalkyl ring; R20 is hydrogen or alkyl; R2a is hydrogen or alkyl; with the proviso that when R26 or R27 is--NHOR2a, then no more than one of R21, R22, R23 and R24 is hydrogen; or single stereoisomers, mixtures of stereoisomers, or pharmaceutically acceptable salts thereof. 21. A compound of Formula IIA: wherein, R51, R53, and R54 are independently hydrogen or alkyl; R56 and R57 are independently selected from: hydrogen, alkyl, and cyano; R59 and R510 together with the carbon atom to which they are attached form a (C3-C4)cycloalkyl ring; or single stereoisomers, mixtures of stereoisomers, or pharmaceutically acceptable salts thereof. 22. The compound of claim 20, wherein R27 is--NR20OR2a. 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, R30 is selected from the group consisting of alkyl, aralkyl, heterocyclyl and aryl; R31, R33, and R34 are independently hydrogen or alkyl; R32 is hydroxy or alkoxy; R35, R36, R37, and R38 are hydrogen or together with the carbon atom to which they are attached form C═O; R39 and R310 together with the carbon atom to which they are attached form a (C3-C4)cycloalkyl ring; m is 1; with the proviso no more than one of R31, R33 and R34 is hydrogen; or single stereoisomers, mixtures of stereoisomers, or pharmaceutically acceptable salts thereof. 28. A compound of Formula IIIA: R60 is selected from the group consisting of alkyl, aralkyl, acyl, heterocyclyl and aryl; R61, R63, and R64 are independently selected from the group consisting of hydrogen or alkyl; R65 R66, R67, and R68 are hydrogen; R69 and R610 together with the carbon atom to which they are attached form a (C3-C4)cycloalkyl ring; with the following provisos: no more than one of R61, R63 and R64 is hydrogen; or single stereoisomers, mixtures of stereoisomers, or pharmaceutically acceptable salts thereof. 29. The compound of claim 27, wherein--CR35R36 is C═O. 30. The compound of claim 27, wherein--CR37R38 is C═O. 31. The compound of claim 27, wherein R35 and R36 are both hydrogen. 32. The compound of claim 27 wherein R30 is alkyl substituted with an amido, a sulfonylamino or an aminosulfonyl group. 33. The compound of claim 32, wherein R30 is--(CH2)2-6--NHS(O)2-aryl,--(CH2)2-6--S(O)2NH-aryl,--(CH2)2-6--NHC(O)-aryl, or--(CH2)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.