# US 9,040,673 B2 · Synthesis and identification of novel RSK-specific inhibitors

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- Number: US 9,040,673 B2
- Document ID: US9040673B2
- Status: Granted
- Kind: B2
- Application number: 13/390,389
- Filed: 2010-08-13
- Published: 2012-09-27
- Granted: 2015-05-26
- Earliest claimed: 2009-08-14
- Assignees: University of Virginia Patent Foundation
- Applicants: Sidney M. Hecht; Deborah A. Lannigan-Macara; Jeffrey Allan Smith; George A. O'Doherty; Michael Kenneth Hilinski
- Inventors: Sidney M. Hecht; Deborah A. Lannigan-Macara; Jeffrey Allan Smith; George A. O'Doherty; Michael Kenneth Hilinski
- Web page: https://patentgrep.com/patent/US9040673B2

## CPC

- A61K 31/535: having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K 31/353: 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K 31/7048: having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin}
- A61P 31/04: Antibacterial agents
- A61P 31/06: for tuberculosis
- A61P 35/00: Antineoplastic agents
- C07H 17/075: Benzo[b]pyran-2-ones
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

A composition comprising an SL0101 [kaempferol 3-O-(3″,4″-di-O-acetyl-α-L-rhamnopyranoside)] derivative compound that has enhanced ability to inhibit RSK activity, relative to the parent compound is provided. The compounds have utility for treating any disease or conditions characterized or associated with excess or undesirable RSK activity. For example the RSK inhibitors of the present invention can be used to reduce the proliferation of neoplastic cells or for inhibiting the establishment or maintenance of an intracellular pathogenic infection by pathogens whose pathogenicity derives in part from the pathogen's ability to impede endosomal/phagosomal maturation in the host cell.

## Claims

### Claim 1

A RSK inhibitor represented by the general structure of Formula III
wherein R1, R3 and R7 are each hydroxyl;
R5, R6, R8 and R9 are each hydrogen;
R10, R11 and R20 are independently selected from the group consisting of hydroxyl, —NHOCOR14, —OCOR14, —COR14 and C1-C4 alkoxy;
X is O or CH2; and
R14 is selected from the group consisting of hydrogen, and C1-C4 alkyl.

### Claim 2 (depends on 1)

The RSK inhibitor of claim 1 wherein
R10, R11 and R20 are independently selected from the group consisting of hydroxyl and —OCOR14, wherein at least one of R10, R11 and R20 is hydroxyl.

### Claim 3 (depends on 2)

The RSK inhibitor of claim 2 wherein
one of R10 and R11 is —OCOCH3 and the other is hydroxyl.

### Claim 4 (depends on 1)

The RSK inhibitor of claim 1 wherein the inhibitor comprise the general structure of Formula IV:
wherein R5, R6, R8 and R9 are each hydrogen;
R10, R11 and R20 are independently selected from the group consisting of —OCOR14, —COR14 and hydroxyl, and R14 is selected from the group consisting of hydrogen and C1-C4 alkyl.

### Claim 5 (depends on 4)

The RSK inhibitor of claim 4 wherein
at least one of R10, R11 and R20 is —OCOCH3, and at least one of R10, R11 and R20 is hydroxyl.

### Claim 6 (depends on 5)

The RSK inhibitor of claim 5 wherein R20 is OCOCH3, and one of R10 and R11 is OCOCH2, and the other is hydroxyl.

### Claim 7 (depends on 4)

The RSK inhibitor of claim 4 wherein R11 and R20 are both OCOCH3, and R10 is hydroxyl.

### Claim 8 (depends on 1)

A pharmaceutical composition comprising a RSK specific inhibitor of claim 1 and a pharmaceutically acceptable carrier.

### Claim 9 (depends on 8)

The composition of claim 8, further comprising an anti-tumor agent.

### Claim 10 (depends on 1)

A method of specifically inhibiting RSK activity, said method comprising the step of contacting a RSK enzyme with the RSK specific inhibitor of claim 1.

### Claim 11 (depends on 6)

A method for treating a disease or condition characterized by inappropriate RSK activation, said method comprising the step of administering to a human or other mammal in need thereof, a composition comprising the RSK specific inhibitor of claim 6 in an amount effective for specifically inhibiting RSK activity in the cells of said human or mammal.

### Claim 12 (depends on 11)

The method of claim 11 wherein the disease is a neoplastic disease.

### Claim 13 (depends on 12)

The method of claim 12 further comprising the step of administering to said patient in an anti-tumour therapy.