# US 2013/0158043 A1 · Pak inhibitors for the treatment of cancer

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2013/0158043 A1
- Document ID: US20130158043A1
- Status: Published application
- Kind: A1
- Application number: 13/708,886
- Filed: 2012-12-07
- Published: 2013-06-20
- Earliest claimed: 2011-12-09
- Assignees: Afraxis, Inc.
- Inventors: David Campbell; Sergio G. Duron
- Web page: https://patentgrep.com/patent/US20130158043A1

## CPC

- C07D 471/04: Ortho-condensed systems
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 31/541: Non-condensed thiazines containing further heterocyclic rings
- A61P 35/00: Antineoplastic agents
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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

## Abstract

Provided herein are methods of utilizing PAK inhibitors for the treatment of cancer. Further provided herein are compounds and formulations utilized for the treatment of cancer.

## Claims

### Claim 1

A method for treating a cell proliferative disorder in an individual in need thereof, comprising administering to the subject a therapeutically effective amount of a PAK inhibitor or a pharmaceutically acceptable salt, solvate or N-oxide thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the cell proliferative disorder is cancer.

### Claim 3 (depends on 2)

The method of claim 2, wherein the cancer is a breast cancer, colorectal cancer, brain cancer, lung cancer, pancreatic cancer, kidney cancer, skin cancer, cancer of the central nervous system, liver cancer, stomach cancer, gastrointestinal cancer, ovarian cancer, leukemia, or lymphoma.

### Claim 4 (depends on 3)

The method of claim 3, wherein the brain cancer is a glioblastoma.

### Claim 5 (depends on 3)

The method of claim 3, wherein the lung cancer is a mesothelioma.

### Claim 6 (depends on 3)

The method of claim 3, wherein the cancer of the central nervous system is a tumor associated with neurofibromatosis type 1 or neurofibromatosis type 2.

### Claim 7 (depends on 6)

The method of claim 6, wherein the tumor associated with neurofibromatosis type 1 or neurofibromatosis type 2 is a neurofibroma, optic glioma, malignant peripheral nerve sheath tumor, schwannoma, ependymoma, or meningioma.

### Claim 8 (depends on 3)

The method of claim 3, wherein the kidney cancer is a renal cell carcinoma.

### Claim 9 (depends on 1)

The method of claim 1, wherein the PAK inhibitor is a compound of Formula IV or a pharmaceutically acceptable salt, solvate or N-oxide thereof:
wherein:
R1 and R2 are each independently H or substituted or unsubstituted alkyl; or R1 and R2 together with the carbon to which they are attached form a C3-C6 cycloalkyl ring;
p is 1, 2 or 3;
ring A is aryl or heteroaryl;
R3 is S(═O)R9 or —S(═O)2R9;
each R4 is independently halogen, —CN, —NO2, —OH, —OCF3, —OCF2H, —OCH2F, —CF3, —SR8, —S(═O)R9, —S(═O)2R9, —NR10S(═O)2R9, —S(═O)2N(R10)2, —OR10, —C(═O)R9, —OC(═O)R9, —CO2R10, —N(R10)2, —C(═O)N(R10)2, —NR10C(═O)R10, —NR10C(═O)OR10, —NR10C(═O)N(R10)2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl or substituted or unsubstituted heterocycloalkyl;
R8 is H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
R9 is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
each R10 is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl, or two R10 together with the atoms to which they are attached form a heterocycle;
s is 0-4;
ring B is aryl or heteroaryl;
each R5 is independently halogen, —CN, —NO2, —OH, —S(═O)R9, —S(═O)2R9, NR10S(═O)2R9, —S(═O)2N(R10)2, —C(═O)R9, —OC(═O)R9, —CO2R10, —N(R10)2, —C(═O)N(R10)2, —NR10C(═O)R10, —NR10C(═O)OR10, —NR10C(═O)N(R10)2, —OR10, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl or substituted or unsubstituted heterocycloalkyl;
r is 0-8;
R7 is H, halogen, —CN, substituted or unsubstituted alkyl, —C(═O)N(R10)2, —CO2R10, —OR10, —N(R10)2, acyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.

### Claim 10 (depends on 9)

The method of claim 9, wherein R3 is (R)—S(═O)R9 or (S)—S(═O)R9.

### Claim 11 (depends on 9)

The method of claim 9, wherein R3 is —S(═O)2R9.

### Claim 12 (depends on 9)

The method of claim 9, wherein R1 and R2 are H; and p is 1.

### Claim 13 (depends on 12)

The method of claim 12, wherein ring A is an aryl ring.

### Claim 14 (depends on 13)

The method of claim 13, wherein ring A is a phenyl ring.

### Claim 15 (depends on 12)

The method of claim 12, wherein ring A is a 5-10-membered heteroaryl ring comprising 0-4 N atoms, 0-2 O atoms, 0-2 S atoms, or any combination thereof; wherein at least one N, S, or O atom is present.

### Claim 16 (depends on 15)

The method of claim 15, wherein ring A is selected from pyrrole, furan, thiophene, pyrazole, imidazole, isoxazole, oxazole, isothiazole, thiazole, 1,2,3-triazole, 1,3,4-triazole, 1-oxa-2,3-diazole, 1-oxa-2,4-diazole, 1-oxa-2,5-diazole, 1-oxa-3,4-diazole, 1-thia-2,3-diazole, 1-thia-2,4-diazole, 1-thia-2,5-diazole, 1-thia-3,4-diazole, tetrazole, pyridine, pyridazine, pyrimidine, and pyrazine.

### Claim 17 (depends on 9)

The method of claim 9, wherein s is 0.

### Claim 18 (depends on 9)

The method of claim 9, wherein ring B is an aryl ring.

### Claim 19 (depends on 9)

The method of claim 9, wherein R5 is independently)-N(R10)2, or substituted or unsubstituted heterocycloalkyl.

### Claim 20 (depends on 19)

The method of claim 19, wherein r is 1; and R5 is substituted or unsubstituted piperazine.