# US 2014/0155366 A1 · Platinum anticancer agents

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- Number: US 2014/0155366 A1
- Document ID: US20140155366A1
- Status: Published application
- Kind: A1
- Application number: 14/175,295
- Filed: 2014-02-07
- Published: 2014-06-05
- Earliest claimed: 2011-08-26
- Assignees: The Regents of the University of California
- Applicants: The Regents of the University of California
- Inventors: Kathleen M. Giacomini; Swati More
- Web page: https://patentgrep.com/patent/US20140155366A1

## CPC

- C07F 15/0093: {without a metal-carbon linkage}
- A61P 35/00: Antineoplastic agents
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Described herein are novel platinum-based compounds and methods of using platinum-based compounds in the treatment of diseases, such as cancer, that are associated with cells expressing solute transporter proteins.

## Claims

### Claim 1

A compound having the formula:
wherein,
X− is a counterion;
R1, R2, and R3 are independently
halogen, —SR9, —OSO2R8, —OSO3H, —NH2NH2, —ONR6R7, —NH2C═(O)NHNH2, —NH2C═(O)NR6R7, —NR5R6R7, —OC(O)R8, —OC(O)NR6R7, —OR9, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl, with the proviso R1, R2, and R3 are attached to the Pt atom through an atom that is not a carbon atom, wherein R1 and R2, R2 and R3 or R1 and R3 may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
R4 is substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R5, R6, R7, R8, and R9 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;
R5 and R6, R6 and R7, or R5 and R7, may optionally be joined to form, in combination with their commonly bonded nitrogen, a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl.

### Claim 2

(canceled)

### Claim 3

(canceled)

### Claim 4

(canceled)

### Claim 5

(canceled)

### Claim 6

(canceled)

### Claim 7

(canceled)

### Claim 8 (depends on 1)

The compound of claim 1, wherein R1 and R2 are independently —SR9, —OSO2R8, —OSO3H, —NH2NH2, —ONR6R7, —NH2C═(O)NHNH2, —NH2C═(O)NR6R7, —NR5R6R7, —OC(O)R8, —OC(O)NR6R7, —OR9, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl, with the proviso R1 and R2 are attached to the Pt atom through an atom that is not a carbon atom; and
R3 is halogen.

### Claim 9 (depends on 8)

The compound of claim 8, wherein R1 and R2 are independently —NH3.

### Claim 10 (depends on 8)

The compound of claim 8, wherein R3 is —Cl.

### Claim 11 (depends on 1)

The compound of claim 1, wherein R1 and R3 are independently —SR9, —OSO2R8, —OSO3H, —NH2NH2, —ONR6R7, —NH2C═(O)NHNH2, —NH2C═(O)NR6R7, —NR5R6R7, —OC(O)R8, —OC(O)NR6R7, —OR9, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl, with the proviso R1 and R3 are attached to the Pt atom through an atom that is not a carbon atom; and
R2 is halogen.

### Claim 12 (depends on 11)

The compound of claim 11, wherein R1 and R3 are independently —NH3.

### Claim 13 (depends on 11)

The compound of claim 11, wherein R2 is —Cl.

### Claim 14 (depends on 1)

The compound of claim 1, wherein R4 is substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.

### Claim 15

(canceled)

### Claim 16 (depends on 14)

The compound of claim 14, wherein R4 is substituted or unsubstituted phenyl.

### Claim 17

(canceled)

### Claim 18

(canceled)

### Claim 19 (depends on 16)

The compound of claim 16, having the formula:
wherein,
R10 is independently halogen, —CY3, —CN, —SO2Cl, —SOqR14, —SOuNR11R12, —NHNH2, —NR11R12, —NHC═(O)NHNH2, —NHC═(O)NR11R12, —N(O)m, —NR11R12, —C(O)R13, —C(O)—OR13, —C(O)NR11R12, —OR14, 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;
two adjacent R10 substituents may optionally be joined to form a substituted or unsubstitued cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R11, R12, R13, and R14 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;
z is an integer from 0 to 5;
u is independently an integer from 1 to 2;
m is independently an integer from 1 to 2;
q is independently an integer from 0 to 4;
Y is independently —Cl, —Br, —I, or —F.

### Claim 20

(canceled)

### Claim 21

(canceled)

### Claim 22

(canceled)

### Claim 23 (depends on 19)

The compound of claim 19, having the formula:

### Claim 24 (depends on 23)

The compound of claim 23, having the formula:

### Claim 25 (depends on 16)

The compound of claim 16, having the formula:

### Claim 26 (depends on 1)

A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 1 or a pharmaceutically acceptable salt thereof.

### Claim 27 (depends on 1)

A method of treating a disease in a patient in need of such treatment, said method comprising administering a therapeutically effective amount of a compound of claim 1.

### Claim 28

(canceled)

### Claim 29 (depends on 27)

The method of claim 27, wherein said disease is colorectal cancer, liver cancer, hepatocarcinoma, renal cancer, renal cell carcinoma, bladder cancer, lung cancer, non-small cell lung cancer, ovarian cancer, uterine cancer, cervical cancer, testicular cancer, anal cancer, bile duct cancer, biliary tract cancer, gastrointestinal carcinoid tumors, esophageal cancer, gall bladder cancer, appendix cancer, small intestine cancer, stomach (gastric) cancer, urinary bladder cancer, genitourinary tract cancer, endometrial cancer, head and neck cancer, nasopharyngeal cancer, head and neck squamous cell carcinoma, mesothelioma, lymphoma, leukemia, breast cancer, or prostate cancer.

### Claim 30

(canceled)

### Claim 31 (depends on 27)

The method of claim 27, further comprising a method of measuring the amount of an organic cation transporter in a sample from the patient.

### Claim 32

(canceled)

### Claim 33

(canceled)

### Claim 34

(canceled)

### Claim 35

(canceled)

### Claim 36

(canceled)

### Claim 37 (depends on 1)

A method of inhibiting replication of DNA in a cell, wherein said method comprises contacting said cell with the compound of claim 1.

### Claim 38

(canceled)

### Claim 39 (depends on 1)

A method of inducing cell death in a cell, wherein said method comprises contacting said cell with the compound of claim 1.

### Claim 40

(canceled)

### Claim 41

(canceled)

### Claim 42 (depends on 1)

A method of treating a disease in a patient in need of such treatment, said method comprising administering a therapeutically effective amount of a compound of claim 1,
wherein said patient has disease-related cells expressing a norepinephrine transporter protein or mRNA.

### Claim 43

(canceled)

### Claim 44

(canceled)

### Claim 45

(canceled)

### Claim 46

(canceled)

### Claim 47

(canceled)

### Claim 48

(canceled)

### Claim 49

(canceled)

### Claim 50

(canceled)

### Claim 51

(canceled)

### Claim 52

(canceled)