Anti-cancer polyketide compounds

Patent metadata

Field	Value
Publication number	US-9604973-B2
Application number	US-201414498934-A
Country	US
Kind code	B2
Filing date	Sep 26, 2014
Priority date	Mar 26, 2012
Publication date	Mar 28, 2017
Grant date	Mar 28, 2017

Abstract

Provided herein, inter alia, are anticancer polyketides. The uses of the polyketides described herein include treatment of cancer, for example, through regulation of the spliceosome and detection of spliceosome inhibition.

First claim

What is claimed is:

1. A compound having the formula:

wherein,
X 1 is N, O, or CH 2 ;
X 2 is O or C(R 6 )(R 7 ); and when X 2 is O then:
(i) the chiral carbon at R 2 has (R) stereochemistry and the chiral carbon at R 4 has (S) stereochemistry, and the compound is optically pure; or
(ii) the chiral carbon at R 2 has (S) stereochemistry and the chiral carbon at R 4 has (R) stereochemistry, and the compound is optically pure;

R 6 and R 7 are independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, —OR 12 , —OC(O)R 12 , —OC(O)OR 12 , or —OC(O)NR 13 R 14 ;
R 1 is —C(O)R 8 ;
R 2 is hydrogen or unsubstituted alkyl;
R 4 is —OR 9 ;
R 8 and R 9 are independently hydrogen or unsubstituted alkyl;
R 12 , R 13 and R 14 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and
R 15 is hydrogen or unsubstituted alkyl.

2. The compound of claim 1 , having the formula:

3. The compound of claim 1 , wherein R 15 is hydrogen or C 1 -C 4 unsubstituted alkyl.

4. The compound of claim 3 wherein R 15 is methyl.

5. The compound of claim 2 wherein R 9 is hydrogen.

6. The compound of claim 4 , wherein X 2 is O.

7. The compound of claim 1 , wherein X 2 is C(R 6 )(R 7 ).

8. The compound of claim 7 , wherein R 6 and R 7 are independently hydrogen, halogen, or methyl.

9. The compound of claim 8 , wherein R 6 and R 7 are hydrogen or —F.

10. The compound of claim 1 having the formula:

11. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutical excipient.

12. A method of abating cancer, the method comprising administering to a subject in need thereof a therapeutically effective amount the compound of claim 1 .

13. The method of claim 12 , wherein the cancer is leukemia, lymphoma, metastatic cancer, or bone cancer.

14. The compound of claim 1 , wherein when X 2 is oxygen then the chiral carbon at R 2 has (R) stereochemistry and the chiral carbon at R 4 has (S) stereochemistry, and the compound is optically pure.

Assignees

• Univ California

Inventors

• Burkart Michael D
• La Clair James J
• Jones Brian D
• Mandel Alexander
• Villa Reymundo
• Castro Januario E
• Kashyap Manoj Kumar
• Kumar Deepak

Classifications

• C07D407/06 Primary

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D313/00

  Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom · CPC title