Phenethyldihydrobenzodioxolones and methods of use

1. A compound according to formula:

or stereoisomers thereof, wherein R 1 is selected from the group consisting of methoxy, ethoxy, —SCH 3 , —SCH 2 CH 3 , and —NR 8 R 9 ; R 2 is selected from the group consisting of hydrogen, hydroxyl, alkoxy, amino, aminoalkyl, aminoalkenyl, aminoalkynyl, halide, haloalkyl, hydroxyalkyl, —NHCN, aminocarbonyl, hydroxyaminocarbonyl, alkylaminocarbonyl, acyloxy, nitrile, —CH 2 CN, lower alkyl, substituted lower alkyl, lower alkenyl, lower alkynyl, —SH, —SCH 3 , alkoxycarbonyl, alkylcarbonylamino, —NHC(O)—O-lower alkyl, —NHC(O)—O-lower alkenyl, —NHC(O)—O-lower alkynyl, —NHCO-cyclopropyl, —NHCO— haloalkyl, —NHSO 2 CH 3 , —NHCSNHCH 3 , sulfoximine, —CH═NOH, —SOCH 3 , —SO 2 CH 3 , —NHSO 2 CH 3 , and —SO 2 NH 2 ; R 3 is selected from the group consisting of hydrogen, halide, haloalkyl, hydroxyl, amino, methylamino, —CH 2 OH, methoxy, lower alkyl, lower alkenyl, lower alkynyl, acyloxy, alkylcarbonylamino, —C(O)OCH 3 , nitrile, and —CH 2 CN; R 4 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkoxy, alkoxyalkyl, alkoxyalkenyl, alkoxyalkynyl, alkyl ether, alkylthio, alkenylthio, alkynylthio, thioalkyl ether; R 8 and R 9 are independently selected from the group consisting of hydrogen, lower alkyl, substituted lower alkyl, lower alkenyl, and cycloalkyl, or pharmaceutically acceptable salts, solvates, or prodrugs thereof; provided that R 2 is not methoxy when R 1 is methoxy, R 3 is hydrogen, and R 4 is 2-propenyl.

2. A compound as set forth in claim 1 wherein R 2 is selected from the group consisting of hydrogen, hydroxyl, alkoxy, amino, aminoalkyl, aminoalkenyl, halide, haloalkyl, aminocarbonyl, hydroxyaminocarbonyl, alkylaminocarbonyl, acyloxy, nitrile, —CH 2 CN, lower alkyl, lower alkenyl, alkoxycarbonyl, and alkylcarbonylamino; R 3 is selected from the group consisting of hydrogen, halide, haloalkyl, lower alkyl, ethenyl, ethynyl, acyloxy, —C(O)OCH 3 , nitrile, and —CH 2 CN; R 4 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkoxyalkyl, alkoxyalkenyl, alkoxyalkynyl, alkyl ether, alkylthio, alkenylthio, alkynylthio, and thioalkyl ether; and R 8 and R 9 are independently selected from the group consisting of hydrogen and lower alkyl.

3. A compound as set forth in claim 1 wherein R 1 is selected from the group consisting of methoxy, —NHCH 3 , —N(CH 3 ) 2 ; R 2 is selected from the group consisting of hydrogen, hydroxyl, alkoxy, amino, aminoalkyl, aminoalkenyl, halide, haloalkyl, aminocarbonyl, hydroxyaminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, acetoxy, propionyloxy, nitrile, —CH 2 CN, lower alkyl, ethenyl, ethynyl, alkoxycarbonyl, and alkylcarbonylamino; R 3 is selected from the group consisting of hydrogen, halide, haloalkyl, methyl, ethyl, propyl, acetoxy, —C(O)OCH 3 , nitrile, and —CH 2 CN; R 4 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkoxyalkyl, alkoxyalkenyl, alkoxyalkynyl, alkyl ether and thioalkyl ether.

4. A compound as set forth in claim 3 wherein R 2 is selected from the group consisting of hydrogen, hydroxyl, methoxy, ethoxy, amino, —NHCH 3 , halide, methyl, ethyl, propyl, ethenyl, ethynyl, aminocarbonyl, hydroxyaminocarbonyl, methylaminocarbonyl, acetoxy, propionyloxy, nitrile, —CH 2 CN, alkoxycarbonyl, and alkylcarbonylamino.

5. A compound as set forth in claim 3 wherein R 2 is selected from the group consisting of hydrogen, hydroxyl, amino, fluoro, chloro, methyl, ethyl, aminocarbonyl, hydroxyaminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, acetoxy, nitrile, methylcarbonylamino, ethylcarbonylamino, and propylcarbonylamino; R 3 is selected from the group consisting of hydrogen, fluoro, chloro, methyl, ethyl, acetoxy, —C(O)OCH 3 , nitrile, and —CH 2 CN; R 4 is selected from the group consisting of substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, and thioalkyl ether.

6. A compound as set forth in claim 3 wherein R 4 is selected from the group consisting of substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, and substituted lower alkynyl.

7. A compound as set forth in claim 3 wherein R 4 is selected from the group consisting of lower alkyl, lower alkenyl, and lower alkynyl.

8. A compound as set forth in claim 3 wherein R 4 is selected from the group consisting of ethyl, propyl, butyl, 1-methylpropyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-propynyl, and 2-propynyl.

9. A compound as set forth in claim 1 , or enantiomers thereof, wherein R 1 is selected from the group consisting of methoxy; wherein R 2 is selected from the group consisting of hydrogen, hydroxyl, amino, fluoro, chloro, methyl, ethyl, propyl, ethenyl, propenyl, haloalkyl, aminoalkyl, aminoalkenyl, alkoxy, aminocarbonyl, methylaminocarbonyl, ethylcarbonylamino, acetoxy, propionyloxy, nitrile, —CH 2 CN, —C(O)OCH 3 , ethylcarbonylamino, and methylcarbonylamino; R 3 is selected from the group consisting of hydrogen, fluoro, chloro, methyl, ethyl, propyl, haloalkyl, acetoxy, —C(O)OCH 3 , nitrile, and —CH 2 CN; R 4 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkoxyalkyl, alkoxyalkenyl, alkoxyalkynyl, alkyl ether, and thioalkyl ether.

10. A compound as set forth in claim 9 wherein R 4 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl and thioalkyl ether.

11. A compound as set forth in claim 9 wherein R 4 is selected from the group consisting of lower alkyl, lower alkenyl, and lower alkynyl.

12. A compound as set forth in claim 9 wherein R 4 is selected from the group consisting ethyl, propyl, butyl, 1-methylpropyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-propynyl, and 2-propynyl.

13. A compound according to claim 1 having the formula:

or enantiomers thereof, wherein R 2 is selected from the group consisting of hydrogen, hydroxyl, alkoxy, amino, aminoalkyl, aminoalkenyl, halide, haloalkyl, aminocarbonyl, hydroxyaminocarbonyl, alkylaminocarbonyl, acyloxy, nitrile, —CH 2 CN, lower alkyl, lower alkenyl, alkoxycarbonyl, and alkylcarbonylamino; R 3 is selected from the group consisting of hydrogen, halide, haloalkyl, lower alkyl, lower alkenyl, acyloxy, —C(O)OCH 3 , nitrile, and —CH 2 CN.

14. A compound as set forth in claim 13 wherein R 2 is selected from the group consisting of hydrogen, hydroxyl, amino, fluoro, chloro, methyl, ethyl, propyl, ethenyl, propenyl, haloalkyl, aminoalkyl, aminoalkenyl, alkoxy, aminocarbonyl, methylaminocarbonyl, ethylcarbonylamino, acetoxy, propionyloxy, nitrile, —CH 2 CN, —C(O)OCH 3 , ethylcarbonylamino, and methylcarbonylamino; R 3 is selected from the group consisting of hydrogen, fluoro, chloro, methyl, ethyl, propyl, acetoxy, —C(O)OCH 3 , nitrile, and —CH 2 CN.

15. A compound according to claim 1 having the formula:

or enantiomers thereof, wherein R 2 is selected from the group consisting of hydrogen, fluoro, hydroxyl, chloro, methyl, ethyl, propyl, ethenyl, propenyl, and haloalkyl; R 3 is selected from the group consisting of hydrogen, fluoro, chloro, methyl, ethyl, and propyl, and haloalkyl; R 4 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl and thioalkyl ether; and wherein R 8 and R 9 are independently selected from the group consisting of hydrogen, methyl, ethyl, propyl, ethenyl, propenyl, and cycloalkyl.

16. A compound as set forth in claim 15 wherein R 8 and R 9 are independently selected from the group consisting of hydrogen, methyl, and ethyl.

17. A compound according to claim 1 having the formula:

or enantiomers thereof, wherein R 2 is selected from the group consisting of hydrogen, methoxy, fluoro, chloro, methyl, ethyl, propyl, aminocarbonyl, methylaminocarbonyl, acetoxy, nitrile, and methylcarbonylamino; R 3 is selected from the group consisting of hydrogen, fluoro, chloro, methyl, ethyl, haloalkyl, and acetoxy; and wherein R 8 and R 9 are independently selected from the group consisting of hydrogen, methyl, ethyl, propyl, ethenyl, propenyl, and cycloalkyl.

18. A compound according to claim 1 having the formula:

or enantiomers thereof, wherein R 1 is selected from the group consisting of methoxy and ethoxy; R 2 is selected from the group consisting of hydrogen, hydroxyl, amino, fluoro, chloro, methyl, ethyl, propyl, ethenyl, propenyl, haloalkyl, aminoalkyl, aminoalkenyl, alkoxy, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, acetoxy, propionyloxy, nitrile, —CH 2 CN, —C(O)OCH 3 , ethylcarbonylamino, and methylcarbonylamino; R 3 is selected from the group consisting of halide, hydroxyl, methoxy, lower alkyl, lower alkenyl, haloalkyl, acetoxy, —C(O)OCH 3 , nitrile, and —CH 2 CN; R 4 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, and substituted lower alkenyl, lower alkynyl, and substituted lower alkynyl, or pharmaceutically acceptable salts, or solvates thereof.

19. A compound according to claim 1 having the formula:

or enantiomers thereof, wherein R 2 is selected from the group consisting of hydrogen, fluoro, chloro, methyl, and ethyl; R 3 is selected from the group consisting of hydrogen, fluoro, chloro, methyl, ethyl, —CH 2 Cl, nitrile, and —CH 2 CN; R 4 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, and thioalkyl ether; and wherein R 8 and R 9 are independently selected from the group consisting of hydrogen, lower alkyl, or pharmaceutically acceptable salts, or solvates thereof.

20. A compound as set forth in claim 19 wherein R 4 is selected from the group consisting of lower alkyl, lower alkenyl, and lower alkynyl, and R 8 and R 9 are independently selected from the group consisting of hydrogen and methyl.

21. A compound according to claim 1 having the formula:

or enantiomers thereof, wherein R 2 is selected from the group consisting of hydrogen, hydroxyl, amino, fluoro, chloro, methyl, ethyl, propyl, ethenyl, propenyl, haloalkyl, aminoalkyl, aminoalkenyl, alkoxy, aminocarbonyl, methylaminocarbonyl, ethylcarbonylamino, acetoxy, propionyloxy, nitrile, —CH 2 CN, —C(O)OCH 3 , ethylcarbonylamino, and methylcarbonylamino; R 3 is selected from the group consisting of fluoro, chloro, methyl, ethyl, —CH 2 Cl, acetoxy, —C(O)OCH 3 , nitrile, and —CH 2 CN; R 4 is selected from the group consisting of ethyl, propyl, butyl, 1-methylpropyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-propynyl, and 2-propynyl, or pharmaceutically acceptable salts, or solvates thereof.

22. A compound selected from the group consisting of:

or enantiomers thereof, or pharmaceutically acceptable salts, or solvates thereof.

23. A compound according to claim 22 having the chemical structure:

wherein the compound is the (+)-enantiomer.

24. A compound selected from the group consisting of:

or enantiomers thereof, or pharmaceutically acceptable salts, or solvates thereof.

25. A compound according to claim 24 having the chemical structure:

wherein the compound is the (+)-enantiomer.

26. A compound selected from the group consisting of:

or enantiomers thereof, or pharmaceutically acceptable salts, or solvates thereof.

27. A compound according to claim 26 , having the chemical structure:

wherein the compound is the (+)-enantiomer.

28. A compound selected from the group consisting of:

or enantiomers thereof, or pharmaceutically acceptable salts, or solvates thereof.

29. A compound selected from the group consisting of:

or pharmaceutically acceptable salts, or solvates thereof, wherein the compound is the (+)-enantiomer.

30. A compound selected from the group consisting of:

6-allyl-7a-(1-(2-fluoro-4-methoxyphenyl)propan-2-yl)-7,7a-dihydrobenzo[d][1,3]dioxol-5 (6H)-one,

6-allyl-7a-(1-(2-fluoro-5-hydroxy-4-methoxyphenyl)propan-2-yl)-7,7a-dihydrobenzo[d][1,3]dioxol-5(6H)-one,

6-allyl-7a-(1-(2,5-difluoro-4-methoxyphenyl)propan-2-yl)-7,7a-dihydrobenzo[d][1,3]dioxol-5 (6H)-one,

6-allyl-7a-(1-(2,5-difluoro-4-(methylamino)phenyl)propan-2-yl)-7,7a-dihydrobenzo[d][1,3]dioxol-5(6H)-one,

7a-(1-(2-fluoro-4-methoxyphenyl)propan-2-yl)-7,7a-dihydro-6-propylbenzo[d][1,3]dioxol-5 (6H)-one,

7a-(1-(2-fluoro-5-hydroxy-4-methoxyphenyl)propan-2-yl)-7,7a-dihydro-6-propylbenzo[d][1,3]dioxol-5(6H)-one,

7a-(1-(2,5-difluoro-4-methoxyphenyl)propan-2-yl)-7,7a-dihydro-6-propylbenzo[d][1,3]dioxol-5(6H)-one,

7a-(1-(2,5-difluoro-4-(methylamino)phenyl)propan-2-yl)-7,7a-dihydro-6-propylbenzo[d][1,3]dioxol-5(6H)-one,

6-(but-3-en-2-yl)-7a-(1-(2-fluoro-4-methoxyphenyl)propan-2-yl)-7,7a-dihydrobenzo[d][1,3]dioxol-5(6H)-one,

6-(but-3-en-2-yl)-7a-(1-(2-fluoro-5-hydroxy-4-methoxyphenyl)propan-2-yl)-7,7a-dihydrobenzo[d][1,3]dioxol-5(6H)-one,

6-(but-3-en-2-yl)-7a-(1-(2,5-difluoro-4-methoxyphenyl)propan-2-yl)-7,7a-dihydrobenzo[d][1,3]dioxol-5(6H)-one,

6-(but-3-en-2-yl)-7a-(1-(2,5-difluoro-4-(methylamino)phenyl)propan-2-yl)-7,7a-dihydrobenzo[d][1,3]dioxol-5(6H)-one, or

pharmaceutically acceptable salts, or solvates thereof.

31. A compound according to the formula:

or stereoisomers thereof, wherein R 1 is selected from the group consisting of methoxy, ethoxy, —SCH 3 , —NHCH 3 , and —N(CH 3 ) 2 ; R 2 is selected from the group consisting of hydrogen, hydroxyl, methoxy, ethoxy, amino, aminoalkyl, aminoalkenyl, fluoro, chloro, aminocarbonyl, hydroxyaminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, acetoxy, nitrile, lower alkyl, lower alkenyl, lower alkynyl, alkoxycarbonyl, and alkylcarbonylamino; R 3 is selected from the group consisting of hydrogen, fluoro, chloro, lower alkyl, lower alkenyl, haloalkyl, acetoxy, —C(O)OCH 3 , nitrile, and —CH 2 CN; R 4 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkoxyalkyl, alkoxyalkenyl, alkoxyalkynyl, alkyl ether, and thioalkyl ether; R 6 is selected from the group consisting of hydrogen, halide, methoxy, ethoxy, methyl, ethyl, propyl, nitrile, and acetoxy; R 7 is selected from the group consisting of hydrogen, halide, hydroxyl, amino, methoxy, ethoxy, methyl, ethyl, propyl, nitrile, and acetoxy, or pharmaceutically acceptable salts, or solvates thereof; provided that when R 2 is hydrogen R 3 is not hydrogen and only one of either R 6 or R 7 are hydrogen; R 2 , R 3 , R 6 , and R 7 are all not hydrogen; and R 2 is not methoxy when R 1 is methoxy, R 3 , R 5 , and R 6 are hydrogen, and R 4 is 2-propenyl.

32. A compound as set forth in claim 31 , or enantiomers thereof, wherein R 1 is selected from the group consisting of methoxy; R 2 is selected from the group consisting of hydrogen, hydroxyl, amino, aminoalkyl, aminoalkenyl, fluoro, chloro, aminocarbonyl, hydroxyaminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, nitrile, methyl, ethyl, propyl, ethenyl, ethynyl, 2-propenyl, 3-propenyl, ethynyl, alkoxycarbonyl, and alkylcarbonylamino; R 3 is selected from the group consisting of hydrogen, fluoro, chloro, methyl, ethyl, ethenyl, ethynyl, —CH 2 Cl, nitrile, and —CH 2 CN; R 4 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkyl ether, and thioalkyl ether.

33. A compound as set forth in claim 31 , or enantiomers thereof, wherein R 2 is selected from the group consisting of hydrogen, hydroxyl, fluoro, chloro, methyl, nitrile, and methylcarbonylamino; R 3 is selected from the group consisting of hydrogen, fluoro, chloro, methyl, ethyl, —CH 2 Cl, nitrile, and —CH 2 CN; R 4 is selected from the group consisting of ethyl, propyl, butyl, 1-methylpropyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-propynyl, and 2-propynyl, alkoxyalkyl, alkoxyalkenyl, alkoxyalkynyl, and thioalkyl ether.

34. A compound having the chemical structure:

or stereoisomers thereof, or pharmaceutically acceptable salts and solvates thereof.

35. A compound having the chemical structure:

or stereoisomers thereof, or pharmaceutically acceptable salts and solvates thereof.

36. A compound according to claim 1 having the formula:

or enantiomers thereof, wherein R 3 is selected from the group consisting of hydrogen, fluoro, chloro, methyl, ethyl, propyl, ethenyl, ethynyl, acetoxy, —CH 2 Cl, —C(O)OCH 3 , nitrile, and —CH 2 CN; R 4 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkyl ether, and thioalkyl ether, or pharmaceutically acceptable salts, solvates, or prodrugs thereof.

37. A compound as set forth in claim 36 wherein R 3 is selected from the group consisting of hydrogen, fluoro, chloro, and methyl; R 4 is selected from the group consisting of lower alkyl, lower alkenyl, and lower alkynyl.

38. A compound according to claim 1 having the formula:

or enantiomers thereof, wherein R 2 is selected from the group of hydroxyl and aminocarbonyl; R 3 is selected from the group consisting of hydrogen and fluoro; R 4 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkyl ether, and thioalkyl ether, or pharmaceutically acceptable salts, solvates, or prodrugs thereof.

39. A compound according to the formula:

or enantiomers thereof, wherein R 2 is selected from the group consisting of —NHCO—C 1 —O 5 alkyl, —NHCO—C 2 —O 5 alkenyl, —NHC(O)—O—C 1 -C 5 alkyl, —NHC(O)—O—C 2 —O 5 alkenyl, and said alkyl and alkenyl groups may be optionally substituted by independent replacement of one, two, or three hydrogen atoms thereon with substituents selected from the group consisting of methoxy, ethoxy, propoxy, isopropoxy, gem-dimethyl, cyclopropyl, oxo, sulfoxide, acetoxy, hydroxyl, halide, CF 3 , CCl 3 , nitrile, amino, methylamino, dimethylamino, ethylamino, diethylamino, tert-butylamino, aminocarbonyl, methylaminocarbonyl, methylcarbonylamino, —CH═NOH, —COOH, —SOCH 3 , —SO 2 CH 3 , —NHSO 2 CH 3 , —SO 2 NH 2 , —C(O)OCH 3 , —C(O)CH 3 , —SH, —SCH 3 , and —SCH 2 CH 3 ; R 3 is selected from the group consisting of hydrogen and fluoro; R 4 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkyl ether, and thioalkyl ether, or pharmaceutically acceptable salts, solvates, or prodrugs thereof.

40. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of claim 1 .

41. A method of treating cancer in a patient which comprises providing an effective amount of a compound of claim 1 .

42. A method of treating hyperproliferative cellular disease in a patient which comprises providing an effective amount of a compound of claim 1 .

43. A method of treating inflammatory disease in a patient which comprises providing an effective amount of a compound of claim 1 to said patient.