Novel boronic chalcone derivatives and uses thereof

• US 20050176988A1
• Filed: 06/12/2003
• Published: 08/11/2005
• Est. Priority Date: 06/13/2002
• Status: Active Grant

• Current Assignee: Johns Hopkins University, Johns Hopkins Technology Transfer
• Original Assignee: Johns Hopkins University, Johns Hopkins Technology Transfer
• Inventors: Khan, Saeed R.
• Granted Patent: US 7,514,579 B2
• Time in Patent Office: Days
• US Class Current: 562/7
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds

Abstract

The present invention relates to novel boronic chalcone derivatives which are useful as antitumor/anticancer agents. The present compounds, which are inexpensive to synthesize, exhibit unexpectedly good inhibitors of the growth of human breast cancer cells. The present invention also relates to the use of the novel boronic chalcone derivatives to treat cancer. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing the inhibitors and pharmaceutical compositions in the treatment and prevention of cancer.

Claims

1. A compound including resolved enantiomers, diastereomers, solvates and pharmaceutically acceptable salts thereof, said compound having the Formula (I):

2. The compound of claim 1 having the structure

3. The compound of claim 1 having the structure

4. The compound of claim 1 having the structure

5. The compound of claim 1 having the structure

6. The compound of claim 1 having the structure

7. The compound of claim 1 having the structure

8. The compound of claim 1 having the structure

9. The compound of claim 1 having the structure

10. A compound including resolved enantiomers, diastereomers, solvates and pharmaceutically acceptable salts thereof, said compound having the Formula (II):

11. The compound of claim 10, wherein R³ is fluoro, chloro, bromo, iodo, NO₂, NH₂, CN, SO₂R¹, SO₂Ar, COOH, OAr, COOR¹, OR¹, COR¹, SH, SR¹, OH, CF₃, Ar, alkenyl, alkynyl or allyl, wherein said OAr, Ar, alkenyl, alkynyl and allyl may be optionally unsubstituted or substituted with an electron withdrawing moiety

12. A compound including resolved enantiomers, diastereomers, solvates and pharmaceutically acceptable salts thereof, said compound having the Formula (III):

13. A method of treating a tumor or cancer in a patient in need thereof comprising administering to said patient an effective amount of a compound having the Formula (I):

14. The method of claim 13, wherein said tumor is selected from the group consisting of breast, cervical, stomach, colon, bladder, rectal, liver, pancreatic, lung, cervix uteri, corpus uteri, ovary, prostate, testis, renal, brain/cns, head, neck, throat, anal and oral cancers, eye or ocular cancer, skin melanoma, Ewing'"'"'s Sarcoma, Kaposi'"'"'s Sarcoma, basal cell carcinoma and squamous cell carcinoma, small cell lung cancer, mouth/pharynx, esophageal, larynx, kidney and lymphoma, acute lymphocytic leukemia, and acute myelogenous leukemia,

15. A method of treating a tumor or cancer in a patient in need thereof comprising administering to said patient an effective amount of a compound having the Formula (II):

16. The method of claim 15, wherein said tumor is selected from the group consisting of breast, cervical, stomach, colon, bladder, rectal, liver, pancreatic, lung, cervix uteri, corpus uteri, ovary, prostate, testis, renal, brain/cns, head, neck, throat, anal and oral cancers, eye or ocular cancer, skin melanoma, Ewing'"'"'s Sarcoma, Kaposi'"'"'s Sarcoma, basal cell carcinoma and squamous cell carcinoma, small cell lung cancer, mouth/pharynx, esophageal, larynx, kidney and lymphoma, acute lymphocytic leukemia, and acute myelogenous leukemia.

17. A method of treating a tumor or cancer in a patient in need thereof comprising administering to said patient an effective amount of a compound having the Formula (III):

18. The method of claim 17, wherein said tumor is selected from the group consisting of breast, cervical, stomach, colon, bladder, rectal, liver, pancreatic, lung, cervix uteri, corpus uteri, ovary, prostate, testis, renal, brain/cns, head, neck, throat, anal and oral cancers, eye or ocular cancer, skin melanoma, Ewing'"'"'s Sarcoma, Kaposi'"'"'s Sarcoma, basal cell carcinoma and squamous cell carcinoma, small cell lung cancer, mouth/pharynx, esophageal, larynx, kidney and lymphoma, acute lymphocytic leukemia, and acute myelogenous leukemia.

19. A method of inhibiting MDM2 expression in a mammal, comprising administering an amount of a compound effective to inhibit said expression, said compound having the Formula (I):

20. A method of inhibiting MDM2 expression in a mammal, comprising administering an amount of a compound effective to inhibit said expression, said compound having the Formula (II):

21. A method of inhibiting MDM2 expression in a mammal, comprising administering an amount of a compound effective to inhibit said expression, said compound having the Formula (III):