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- Nachgewiesen in: USPTO Patent Applications
- Sprachen: English
- Document Number: 20100184812
- Publication Date: July 22, 2010
- Appl. No: 12/663194
- Application Filed: June 06, 2008
- Assignees: UNIVERSITY OF MARYLAND, BALTIMORE (Baltimore, MD, US)
- Claim: 1. A mutual prodrug compound comprising a histone deacetylase inhibitor (HDACI) linked to a retinoid.
- Claim: 2. The mutual prodrug composition of claim 1, wherein said HDACI is selected from the group consisting of SAHA, CI-994 and MS-275: [chemical expression included]
- Claim: 3. The mutual prodrug compound of claim 1, wherein said retinoid is selected from the group consisting of all-trans retinoic acid (ATRA) and 13-cis retinoic acid (13-CRA).
- Claim: 4. The mutual prodrug compound of claim 1, wherein said retinoid is selected from the group consisting of RAMBAs of formula (I): [chemical expression included] wherein R1 is an azole group, an allylic azole group, a sulfur-containing group, an oxygen-containing group, a nitrogen-containing group, a pyridyl group, an ethinyl group, a cyclopropyl-amine group, an ester group, an amino group, an azido group, or a cyano group, or R1 forms, together with the C-4 carbon atom, an oxime, an oxirane or aziridine group; R2 is a hydroxyl group, an aminophenol group, an ester group, an azole group or —OR3, wherein R3 is selected from the group consisting of an alkyl, an aryl and a heterocyclic group; and wherein, independently, any of the unsaturations may be cis or trans.
- Claim: 5. The mutual prodrug compound of claim 4, where said RAMBA selected from the group consisting of the RAMBAs set forth in Table 1: [table included]
- Claim: 6. The mutual prodrug compound of claim 4, where said RAMBA selected from the group consisting of the VN/12-1, VN/14-1 and VN/16-1.
- Claim: 7. The mutual prodrug composition of claim 1, wherein said HDACI is CI-994 and said retinoid is all-trans retinoic acid (ATRA).
- Claim: 8. The mutual prodrug composition of claim 1, wherein said HDACI is MS-275 and said retinoid is all-trans retinoic acid (ATRA).
- Claim: 9. The mutual prodrug composition of claim 1, wherein said HDACI is linked to said retinoid via a linking group selected from the group consisting of an acyloxyalkyl linker, an (acyloxy)alkyl ester linker, an acyloxymethycarbamate linker, a glycine acyloxyalkyl carbamate linker a 1,6-elimination linker and a 1,4-elimination linker.
- Claim: 10. (canceled)
- Claim: 11. The mutual prodrug composition of claim 9, wherein said HDACI is linked to said retinoid via a linking group selected from the group consisting of a butyric acid and a phenyl butyric acid.
- Claim: 12. The mutual prodrug composition of claim 1, wherein said HDACI is linked to said retinoid via a linking group of the following formula: [chemical expression included] where * and ** are attachment points.
- Claim: 13. The mutual prodrug composition of claim 1, wherein said HDACI is linked to said retinoid via a linking group of the following formula: [chemical expression included] where * and ** are attachment points.
- Claim: 14. The mutual prodrug composition of claim 1, wherein said a histone deacetylase inhibitor (HDACI) linked to a retinoid is selected from the group consisting of: [chemical expression included]
- Claim: 15. A pharmaceutically acceptable mutual prodrug composition comprising the mutual prodrug compound of claim 1 and a pharmaceutically acceptable carrier or an excipient.
- Claim: 16. A method of inhibiting ATRA 4-hydroxylase activity in a subject, comprising administering the pharmaceutically acceptable mutual prodrug composition of claim 15 to a subject, thereby inhibiting ATRA 4-hydroxylase activity in said subject.
- Claim: 17. A method of inhibiting growth of a cell in a subject, comprising administering the pharmaceutically acceptable mutual prodrug composition of claim 15 to a subject, thereby inhibiting the growth of a cell in said subject.
- Claim: 18. A method of treating cancer in a subject, comprising administering the pharmaceutically acceptable mutual prodrug composition of claim 15 to a subject in need of treatment, thereby treating cancer in said subject.
- Claim: 19. The method of claim 18, wherein said cancer is selected from the group consisting of an epithelial tumor, melanoma, leukemia, acute promyelocytic leukemia, lymphoma, osteogenic sarcoma, colon cancer, pancreatic cancer, breast cancer, prostate cancer, ovarian cancer, and lung cancer.
- Claim: 20. (canceled)
- Claim: 21. A compound of structural formula: [chemical expression included]
- Claim: 22. A mutual prodrug compound comprising a butyric acid linked to ATRA.
- Claim: 23. The mutual prodrug compound of claim 22, there the prodrug compound has formula [chemical expression included]
- Claim: 24. A pharmaceutically acceptable mutual prodrug composition comprising the mutual prodrug compound of claim 22 and a pharmaceutically acceptable carrier or an excipient.
- Claim: 25. A method of inhibiting ATRA 4-hydroxylase activity in a subject, comprising administering the pharmaceutically acceptable mutual prodrug composition of claim 24 to a subject, thereby inhibiting ATRA 4-hydroxylase activity in said subject.
- Claim: 26. A method of inhibiting growth of a cell in a subject, comprising administering the pharmaceutically acceptable mutual prodrug composition of claim 24 to a subject, thereby inhibiting the growth of a cell in said subject.
- Claim: 27. A method of treating cancer in a subject, comprising administering the pharmaceutically acceptable mutual prodrug composition of claim 24 to a subject in need of treatment, thereby treating cancer in said subject.
- Claim: 28. The method of claim 27, wherein said cancer is selected from the group consisting of an epithelial tumor, melanoma, leukemia, acute promyelocytic leukemia, lymphoma, osteogenic sarcoma, colon cancer, pancreatic cancer, breast cancer, prostate cancer, ovarian cancer, and lung cancer.
- Claim: 29. (canceled)
- Current U.S. Class: 514/357
- Current International Class: 61; 07; 07; 07; 61; 61; 61
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