Inhibitors of cyclin dependent kinases and their use

1. A method of inhibiting the activity of cyclin-dependent kinases selected from the group consisting of cyclin dependent kinase 2 (CDK2) and cyclin dependent kinase 4 (CDK4), which comprises administering to a mammal, an effective amount of a compound of the formula (Ig), or a stereoisomer, optical isomer, a pharmaceutically acceptable salt, or a pharmaceutically acceptable solvate thereof;

wherein

R 1 is phenyl, which is unsubstituted or substituted by 1, 2, or 3 identical or different substituents selected from: halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, nitro, NR 9 R 10 , SR 11 , trifluoromethyl, hydroxyl, cyano, carboxy, C 1 -C 4 -alkoxycarbonyl and —C 1 -C 4 -alkylenehydroxyl, or is a heterocycle, which is a saturated, partially unsaturated or aromatic ring containing 5 or 6 ring atoms of which 1, 2 or 3 are identical or different heteroatoms selected from: nitrogen, oxygen, sulfur, and phosphorus, and where the heterocycle is unsubstituted or substituted by 1, 2, or 3 identical or different substituents selected from: halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, nitro, NR 9 R 10 , SR 11 , trifluoromethyl, hydroxyl, cyano, carboxy, C 1 -C 4 -alkoxycarbonyl and C 1 -C 4 -alkylenehydroxyl;

R 2 is hydrogen, C 1 -C 6 -alkyl and phenyl, which is unsubstituted or substituted by 1, 2, or 3 identical or different substituents selected from: halogen, C 1 -C 4 -alkyl, C 1 -C 4 alkoxy, nitro, NR 9 R 10 , SR 11 , trifluoromethyl, hydroxyl, cyano, carboxy, C 1 -C 4 -alkoxycarbonyl and —C 1 -C 4 -alkylenehydroxyl; OR 11 , halogen, cyano, nitro, NR 9 R 10 or SR 11 ;

R 3 , R 4 and R 5 are each independently selected from: hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxyl, halogen, OR 11 , C 1 -C 4 -alkylcarbonyloxy, NR 9 R 10 , SO 2 NR 9 R 10 , carboxyl, cyano and nitro;

Z is O or S;

A is a 5-membered saturated ring represented by any one of the general structures (i) to (v);

wherein X 1 and X 2 independently represent a carbon atom and a nitrogen atom provided that at least one of X 1 and X 2 is a nitrogen atom and wherein the nitrogen atom is at least monosubstituted by R 13 , wherein R 13 is selected from: hydrogen, unsubstituted C 1 -C 6 -alkyl, or C 1 -C 6 -alkyl substituted by halogen, hydroxyl, or carboxyl, C 2 -C 6 -alkenyl, hydroxyl, C 1 -C 6 -alkoxy, C 1 -C 4 alkylcarbonyl, toluenesulfonyl, SO 2 R 10 , —CO(CH 2 ) m R 4 ; cyano, phenyl, which is unsubstituted or substituted by 1, 2, or 3 identical or different substituents selected from: halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, nitro, NR 9 R 10 , SR 11 , trifluoromethyl, hydroxyl, cyano, carboxy, C 1 -C 4 -alkoxycarbonyl and -C 1 -C 4 -alkylenehydroxyl;

R 6 is C 1 -C 4 -alkyl, —C 1 -C 4 alkanoyl, hydroxyl, C 1 -C 4 alkoxy, —C 1 -C 4 -alkoxycarbonyl, —C 1 -C 4 -alkyleneOR 11 , —C 1 -C 4 -alkylenehalo, —C 1 -C 4 -alkyleneNR 9 R 10 , —C 1 -C 4 -alkyleneC(O)OR 9 , phenoxy, —NR 9 R 10 , SR 12 , S(O) n R 12 or —C(S)R 12 ;

R 9 and R 10 are each independently selected from: hydrogen, C 1 -C 4- alkyl, C 1 -C 4- alkanoyl, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkylcarbonyl, carboxamide and sulfonamide;

R 11 is hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkanoyl, or C 1 -C 4 -alkoxycarbonyl;

R 12 is hydrogen, halogen, C 1 -C 4 -alkyl, —NR 9 R 10 , halogen, —SH, or —S—C 1 -C 4 -alkyl;

R 14 is hydrogen, C 1 -C 4 -alkyl, hydroxyl, NR 9 R 10 , halogen, SH, or —S—C 1 -C 4- alkyl;

m is an integer of 0 to 6; and

n is an integer of 1 or 2.

2. The method of claim 1 , wherein in the compounds of formula (Ig), R 6 is —C 1 -C 4 -alkylene-OR 11 .

3. The method of claim 1 , wherein in the compounds of formula (Ig);

R 1 is phenyl, which is unsubstituted or substituted by 1, 2, or 3 identical or different substituents selected from: halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, nitro, NR 9 R 10 , SR 11 , trifluoromethyl, hydroxyl, cyano, carboxy, C 1 -C 4 alkoxycarbonyl and —C 1 -C 4 -alkylenehydroxyl, or is a heterocycle, which is a saturated, partially unsaturated or aromatic ring containing 6 ring atoms of which 1, 2 or 3 are identical or different heteroatoms selected from: nitrogen, oxygen and sulfur, and where the heterocycle is unsubstituted or substituted by 1, 2, or 3 identical or different substituents selected from: halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, nitro, NR 9 R 10 , SR 11 , trifluoromethyl, hydroxyl, cyano, carboxy, C 1 -C 4 -alkoxycarbonyl and C 1 -C 4 -alkylenehydroxyl;

R 2 and R 4 are hydrogen;

R 3 and R 5 are each independently selected from: hydroxyl, C 1 -C 4 -alkoxyl and C 1 -C 4 -alkylcarbonyloxy;

Z is O;

A is a saturated 5-membered ring represented by the following formula (i);

R 6 is —C 1 -C 4- alkylene-OR 11 ;

R 9 and R 10 are each independently selected from: hydrogen, C 1 -C 4- alkyl, C 1 -C 4- alkanoyl, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkylcarbonyl, carboxamide and sulfonamide;

R 11 is hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkanoyl, or C 1 -C 4 -alkoxycarbonyl; and

R 13 is hydrogen or C 1 -C 4 -alkyl.

4. The method of claim 1 , wherein in the compounds of formula (Ig);

R 1 is phenyl, which is unsubstituted or substituted by 1, 2, or 3 identical or different substituents selected from: halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, nitro, trifluoromethyl, hydroxyl, cyano, carboxy, C 1 -C 4 -alkoxycarbonyl and —C 1 -C 4 -alkylenehydroxyl, or is a heterocycle, which is a saturated, partially unsaturated or aromatic ring containing 6 ring atoms of which 1, 2 or 3 are identical or different heteroatoms selected from: nitrogen, oxygen and sulfur, and where the heterocycle is unsubstituted or substituted by 1, 2, or 3 identical or different substituents selected from: halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, nitro, NR 9 R 10 , SR 11 , trifluoromethyl, hydroxyl, cyano, carboxy, C 1 -C 4 -alkoxycarbonyl and —C 1 -C 4 -alkylenehydroxyl;

R 2 and R 4 are hydrogen;

R 3 and R 5 are each independently selected from: hydroxyl, C 1 -C 4 -alkoxyl and C 1 -C 4 -alkylcarbonyloxy;

Z is O;

A is a 5-membered saturated ring represented by any one of the general structures (i) to (v);

wherein X 1 and X 2 independently represent a carbon atom and a nitrogen atom, provided that at least one of X 1 and X 2 is a nitrogen atom and wherein the nitrogen atom is at least monosubstituted by R 13 , wherein R 13 is selected from: hydrogen, unsubstituted C 1 -C 6 -alkyl, or C 1 -C 6 -alkyl substituted by halogen, hydroxyl, or carboxyl, C 2 -C 6 -alkenyl, hydroxyl, C 1 -C 6 -alkoxy, C 1 -C 4 -alkylcarbonyl, toluenesulfonyl, SO 2 R 10 , —CO(CH 2 ) m R 14 and phenyl, which is unsubstituted or substituted by 1, 2, or 3 identical or different substituents selected from:

halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, nitro, NR 9 R 10 , SR 11 , trifluoromethyl, hydroxyl, cyano, carboxy, C 1 -C 4 -alkoxycarbonyl and —C 1 -C 4 -alkylenehydroxyl;

R 6 is C 1 -C 4 -alkyl, —C 1 -C 4 -alkanoyl, hydroxyl, C 1 -C 4 -alkoxy, —C 1 -C 4 -alkoxycarbonyl, —C 1 -C 4 -alkyleneOR 11 , —C 1 -C 4 -alkylenehalo, —C 1 -C 4 -alkyleneNR 9 R 10 , —C 1 -C 4 -alkyleneC(O)OR 9 , phenoxy, —NR 9 R 10 , SR 12 , S(O) n R 12 or —C(S)R 12 ;

R 9 and R 10 are each independently selected from: hydrogen, C 1 -C 4- alkyl, C 1 -C 4- alkanoyl, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkylcarbonyl, carboxamide and sulfonamide;

R 11 is hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkanoyl, or C 1 -C 4 -alkoxycarbonyl;

R 12 is hydrogen, halogen, C 1 -C 4 -alkyl, —NR 9 R 10 , or OR 9 ;

R 14 is hydrogen, C 1 -C 4 -alkyl, hydroxyl, —NR 9 R 10 , halogen, —SH, or —S—C 1 -C 4- alkyl;

m is an integer of 0 to 6; and

n is an integer of 1 or 2.

5. The method of claim 1 , wherein the compound of formula (Ig) is selected from the group consisting of:

(+/−)-trans-2-(2-Chloro-phenyl)-8-(2-hydroxymethyl- 1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+)-trans-2-(2-Chloro-phenyl)- 8-(2-hydroxymethyl- 1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+)-trans-2-(2-Chloro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(−)-trans-2-(2-Chloro-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(−)-trans-2-(2-Chloro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-2-(2-Bromo-phenyl)-8-(2-hydroxymethy-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+)-trans-2-(2-Bromo-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-2-(4-Bromo-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+)-trans-2-(4-Bromo-phenyl)-5-hydroxy-8-(2-hydroxymethyl- 1-methyl-pyrrolidin-3-yl)-7-methoxy-chromen-4-one;

(+)-trans-2-(4-Bromo-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-2-(3-Chloro-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+)-trans-2-(3-Chloro-phenyl)-5-hydroxy-8-(2-hydroxymethyl- 1-methyl-pyrrolidin-3-yl)-7-methoxy-chromen-4-one;

(+)-trans-2-(3-Chloro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-8-(2-1-1ydroxymethyl-1-methyl-pyrrolidin-3-yl)-2-(2-iodophenyl)-5,7-dimethoxy-chromen-4-one;

(+)-trans-5,7-Dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-2-(2-iodophenyl)-chromen-4-one;

(+)-trans-2-(2-Fluoro-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+)-trans-2-(2-Fluoro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-2-(3-Fluoro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-2-(3-Fluoro-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+)-trans-2-(2,6-Difluoro-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+)-trans-2-(2,6-Difluoro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+/−)-trans-4-[8-(2-Hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-4-oxo-4H-chromen-2-yl]-benzonitrile;

(+/−)-trans-4-[5,7-Dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-4-oxo-4H-chromen-2-yl]-benzonitrile;

(+)-trans-4-[8-(2-Hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-4-oxo-4H-chromen-2-yl]-benzonitrile;

(+)-trans-4-[5,7-Dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-4-oxo-4H-chromen-2-yl]-benzonitrile;

(+/−)-trans-8-(2-Hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-2-(4-trifluoromethyl-phenyl)-chromen-4-one;

(+/−)-trans-5,7-Dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-2-(4-trifluoromethyl-phenyl)-chromen-4-one;

(+)-trans-8-(2-Hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-2-(4-trifluoromethy-phenyl)-chromen-4-one;

(+)-trans-5,7-Dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-2-(4-trifluoromethy-phenyl)-chromen-4-one;

(−)-trans-8-(2-Hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-2-(4-trifluoromethy-phenyl)-chromen-4-one;

(−)-trans-5,7-Dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-2-(4-trifluoromethy-phenyl)-chromen-4-one;

(+)-trans-8-(2-Hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-2-phenyl-chromen-4-one;

(+)-trans-5,7-Dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-2-phenyl-chromen-4-one;

(+)-trans-8-(2-Hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-2-thiophen-2-yl-chromen-4-one;

(+)-trans-5,7-Dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-2-thiophen-2-yl-chromen-4-one;

(+)-trans-4-[5,7-Dihydroxy-8-(2-Hydroxymethyl-1-methyl-pyrrolidin-3-yl)-4-oxo-4H-chromen-2-yl]-3-methyl-benzonitrile;

(+)-trans-4-[8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-4-oxo-4H-chromen-2-yl]-3-methyl-benzonitrile;

(+/−)-trans-2-(2-Bromo-5-methoxy-phenyl)-8-(2-hydroxymethyl- 1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+/−)-trans-2-(2-Bromo-5-methoxy-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl- 1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-2-(2-Bromo-5-methoxy-phenyl)-8-(2-hydroxymethyl- 1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+)-trans-2-(2-Bromo-5-methoxy-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+/−)-trans-2-(2-bromo-5-hydroxy-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-2-(2-bromo-5-methoxy-phenyl)-8-(2-hydroxymethyl- 1-methyl-pyrrolidin-3-yl)-5,7-chromen-4-one;

(+/−)-trans-2-[(3,5-Bis-trifluoromethyl)-phenyl]-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+/−)-trans-2-[(3,5-Bis-trifluoromethyl)-phenyl]-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-2-(2-Chloro-5-methyl-phenyl)-8-(2-hydroxymethyl- 1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+)-trans-2-(2-Chloro-5-methyl-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-2-(2-Bromo-5-nitro-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+/−)-trans-2-(2-Bromo-5-nitro-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+/−)-trans-2-(2-Chloro-pyridin-3-yl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin -3-yl)-5,7-dimethoxy-chromen-4-one;

(+/−)-trans-2-(2-Chloro-pyridin-3-yl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)chromen-4-one;

(+/−)-trans-2-(2-Bromo-5-nitrophenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dihydroxy-chromen-4-one;

(+)-trans-2-(2-Chloro-pyridin-3-yl)-5,7-dihydroxy-8-(2-hydroxymethyl- 1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+/−)-trans-8-(2-Hydroxymethyl- 1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-2-(4-nitrophenyl)-4H-chromen-4-one;

(+/−)-trans-5,7-Dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-2-(4-nitrophenyl)-chromen-4-one;

(+/−)-trans-2-(4-Aminophenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+/−)-trans-8-(2-Hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-2-(2-methoxy-phenyl)-chromen-4-one;

(+/−)-trans-5,7-Dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-2-(2-hydroxy-phenyl)-chromen-4-one;

(+)-trans-3-Chloro-4-[8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-4-oxo-4H-chromen-2-yl]benzonitrile;

(+)-trans-3-Chloro-4-[5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-4-oxo-4H-chromen-2-yl]benzonitrile;

(+)-trans-2-(4-Bromo-2-chloro-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+)-trans-2-(4-Bromo-2-chloro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+/−)-trans-2-(2-Chloro-4-dimethylamino-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+/−)-trans-2-(2-Chloro-4-methylamino-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+/−)-trans-2-(2-Chloro-4-methoxy-phenyl)-8-(2-hydroxymethyl- 1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+/−)-trans-2-(2-Chloro-4-hydroxy-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+/−)-trans-2-(2-Chloro-5-fluoro-phenyl)-8-(2-hydroxymethyl- 1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+/−)-trans-2-(2-Chloro-5-fluoro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+/−)-trans-2-(2-Chloro-5-methoxy-phenyl)-8-(2-hydroxymethyl- 1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+/−)-trans-2-(2-Chloro-5-hydroxy-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+/−)-trans-2-(2-Chloro-5-methoxy-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+/−)-trans-8-(2-Azidomethyl-1-methyl-pyrrolidin-3-yl)-2-(2-chloro-phenyl)-5,7-dimethoxy-chromen-4-one;

(+/−)-trans-8-(2-Aminomethyl-1-methyl-pyrrolidin-3-yl)-2-(2-chloro-phenyl)-5,7-dimethoxy-chromen-4-one;

(+/−)-trans-8-(2-Aminomethyl-1-methyl-pyrrolidin-3-yl)-2-(2-chloro-phenyl)-5,7-dihydroxy-chromen-4-one;

(+/−)-trans-{3-[2-(2-Chloro-phenyl)-5,7-dimethoxy-4-oxo-4H-chromen-8-yl]-1-methyl-pyrrolidin-2-yl}-acetonitrile;

(+/−)-trans-{3-[2-(2-Chloro-phenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl]-1-methyl-pyrrolidin-2-yl}-acetonitrile;

(+/−)-trans-2-[2-Chloro-phenyl-8-(2-mercaptomethyl-1-methyl-pyrrolidin-3-yl)]-5,7-dimethoxy-chromen-4-one;

(+/−)-trans-2-(2-Chloro-phenyl)-5,7-dihydroxy-8-(2-mercaptomethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+/−)-trans-Acetic acid 3-[2-(2-chloro-phenyl)-5,7-dimethoxy-4-oxo-4H-chromen-8-yl]-1-(4-methoxy-phenyl)-pyrrolidin-2-ylmethyl ester;

(+/−)-trans-2-(2-Chloro-phenyl)-8-[2-hydroxymethyl-1-(4-methoxy-phenyl)-pyrrolidin-3-yl]-5,7-dimethoxy-chromen-4-one;

(+/−)-trans-2-(2-Chloro-phenyl)-5,7-dihydroxy-8-[2-hydroxymethyl-1-(4-methoxy-phenyl)-pyrrolidin-3-yl]-chromen-4-one;

(+/−)-trans-Acetic acid 3-[2-(2-chloro-phenyl)-5,7-dimethoxy-4-oxo-4H-chromen-8-yl]-1-propyl-pyrrolidin-2-ylmethyl ester;

(+/−)-trans-2-(2-Chloro-phenyl)-8-[2-hydroxyrnethyl-1-propyl-pyrrolidin-3-yl]-5,7-dimethoxy-chromen-4-one;

(+/−)-trans-2-(2-Chloro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-propyl-pyrrolidin-3-yl)-chromen-4-one;

(+/−)-trans-2-(2-Chloro-4-nitro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methylpyrrolidin-3-yl)-chromen-4-one;

(+/−)-trans-2-(2-Bromo-4-nitro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methylpyrrolidin-3-yl)-chromen-4-one;

(+/−)-trans-3-Chloro-4-[5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-4-oxo-4H-chromen-2-yl]-benzoic acid;

(+/−)-trans-3-Bromo-4-[5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-4-oxo-4H-chromen-2-yl]-benzoic acid;

(+/−)-trans-2-(2-Chloro-4-fluoro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+/−)-trans-2-(4-Amino-2-chloro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+/−)-trans-2-(2-Bromo-5-fluoro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-l-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+/−)-trans-2-(4-Amino-2-bromo-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+/−)-trans-4-Chloro-3-[5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-4-oxo-4H-chromen-2-yl]-benzoic acid;

(+/−)-trans-4-Bromo-3-[5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-4-oxo-4H-chromen-2-yl]-benzoic acid;

(+/−)-trans-4-Bromo-3-[5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-4-oxo-4H-chromen-2-yl]-N-hydroxy-benzamide;

(+/−)-trans-4-Chloro-3-[5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-4-oxo-4H-chromen-2-yl]-N-hydroxy-benzamide;

(+/−)-trans-3-Chloro-4-[5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-4-oxo-4H-chromen-2-yl]-N-hydroxy-benzamide;

(+/−)-trans-3-Bromo-4-[5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-4-oxo-4H-chromen-2-yl]-N-hydroxy-benzamide;

(+/−)-trans-2-(2,4-Difluoro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl- 1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-2-(2-Chloro-3-fluoro-phenyl)-8-(2-hydroxymethyl- 1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+)-trans-2-(2-Chloro-3-fluoro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-2-(2-Bromo-3-fluoro-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+)-trans-2-(2-Bromo-3-fluoro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-2-(2-Bromo-5-fluoro-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+)-trans-2-(2-Bromo-5-fluoro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-2-(2-Chloro-5-iodo-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+)-trans-2-(2-Chloro-5-iodo-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-2-(2-Bromo-5-chloro-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+)-trans-2-(2-Bromo-5-chloro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+/−)-trans-2-(2-Chloro-phenyl)-5,7-dihydroxy-8-(2-hydroxmethyl-1-methyl-1-oxy-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-2-(2-Bromo-4-nitro-phenyl)-8-(2-hydroxyrnethyl-1-methylpyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+)-trans- 2-(2-Bromo-4-nitro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-2-(4-Amino-2-bromo-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+)-trans-2-(4-Amino-2-bromo-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-2-(2-Bromo-4-methoxy-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one;

(+)-trans-2-(2-Bromo-4-methoxy-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-2-(2-Bromo-4-hydroxy-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one;

(+)-trans-Acetic acid 8-(2-acetoxymethyl-1-methyl-pyrrolidin-3-yl)-5-hydroxy-2-(4-nitro-phenyl)-4-oxo-4H-chromen-7-yl ester;

(+)-trans-2-(2,4-Dichloro-5-fluoro-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one; and

(+)-trans-2-(2,4-Dichloro-5-fluoro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one.