# US 12,215,128 B2 · (Pyridinylmethyl)butanediamine derivatives that chelate copper

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- Number: US 12,215,128 B2
- Document ID: US12215128B2
- Status: Granted
- Kind: B2
- Application number: 17/261,313
- Filed: 2019-07-19
- Published: 2021-08-26
- Granted: 2025-02-04
- Earliest claimed: 2018-07-20
- Assignees: Cold Spring Harbor Laboratory; Depymed, Inc.
- Applicants: Cold Spring Harbor Laboratory; Depymed, Inc.
- Inventors: Nicholas Tonks; Navasona Krishnan; Andreas Grill
- Web page: https://patentgrep.com/patent/US12215128B2

## CPC

- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- C07J 43/003: {not condensed}
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 35/00: Antineoplastic agents
- C07D 213/38: having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07J 9/00: Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
- C07J 9/005: {containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton}
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07J: STEROIDS (seco-steroids C07C)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Compounds of formula: are described herein. The compounds selectively complex copper and are therefore useful both abiotically for measuring and detecting small amounts of copper and, in biological systems, for treating diseases associated with inappropriate copper levels, such as Wilson's disease and gastric cancer.

## Claims

### Claim 1

A compound of formula:
wherein R1, R2, R3 and R4 are chosen independently from hydrogen, (C1-C6)alkyl, (C1-C6)oxaalkyl, and (C1-C6)aminoalkyl, or two adjacent R1, R2, R3 and R4 may form a five-, six-, or seven-membered ring, said five-, six-, or seven-membered ring optionally substituted with one or two substituents chosen from halogen, cyano, hydroxy, (C1-C6)alkyl, (C1-C6)oxaalkyl, and (C1-C6)aminoalkyl;
A is a polycyclic ring system chosen from one of the following ring systems:
said rings optionally substituted with one or more substituents chosen from halogen, hydroxy, (C1-C6)alkyl, oxo, (C1-C6)oxaalkyl, carboxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkoxycarbonyl(C1-C6)alkyl, carboxy(C1-C6)alkyl, amino, and (C1-C6)aminoalkyl;
n is zero or one; and
p is one or two;
with the proviso that, when R1, R2, R3, and R4 are all hydrogen, p is one, and n is zero, the polycyclic ring system A is not a perhydrocyclopenta[a]phenanthrene of formula
attached at the 3-position as shown, in which a substituent at 17 is —CH(CH3)CH2CH2COOH, —CH(CH3)CH2CH2COOCH3, —CH(CH3)CH2CH2CH(OSO3H)CH(CH3)2,
regardless of the remaining substitutions of the ring.

### Claim 2 (depends on 1)

A compound according to claim 1 wherein p is one and A is

### Claim 3 (depends on 2)

A compound according to claim 2 wherein the polycyclic ring system A is a perhydrocyclopenta[a]phenanthrene of formula
substituted with hydroxyl at 6 or 7, in which a substituent at 17 is (C3-C8)alkyl.

### Claim 4 (depends on 1)

A compound according to claim 1 wherein A is a polycyclic ring system chosen from naphthalene, tetralin, decalin, and anthracene.

### Claim 5 (depends on 4)

A compound according to claim 4 wherein p is one.

### Claim 6 (depends on 4)

A compound according to claim 4 wherein p is two.

### Claim 7 (depends on 1)

A compound according to claim 1 wherein A is a polycyclic ring system chosen from quinoline, isoquinoline.

### Claim 8 (depends on 7)

A compound according to claim 7 wherein p is one.

### Claim 9 (depends on 7)

A compound according to claim 7 wherein p is two.

### Claim 10 (depends on 1)

A compound according to claim 1 wherein p is one and A is
wherein dotted lines represent optional double bonds and Q1 and Q2 are independently chosen from carbon and nitrogen.

### Claim 11 (depends on 2)

A compound according to claim 2 wherein said polycyclic ring system is substituted with one or more substituents chosen from hydroxy, methyl, oxo, amino, (C1-C6)aminoalkyl, (C1-C6)oxaalkyl, carboxy, methoxycarbonyl, methoxycarbonyl(C1-C6)alkyl, and carboxy(C1-C6)alkyl.

### Claim 12 (depends on 2)

A compound according to claim 2 wherein said polycyclic ring system is unsubstituted.

### Claim 13 (depends on 1)

A compound according to claim 1 wherein any adjacent pair of R1, R2, R3 and R4, taken together, form a benzene ring.

### Claim 14 (depends on 1)

A compound according to claim 1 wherein R1, R2, R3, and R4 are all hydrogen.

### Claim 15 (depends on 1)

A compound according to claim 1 wherein n is one.

### Claim 16 (depends on 1)

A compound according to claim 1 wherein n is zero.

### Claim 17 (depends on 1)

A compound according to claim 1 wherein A is other than quinoline or isoquinoline.

### Claim 18 (depends on 1)

A method of chelating copper, comprising contacting a sample containing copper with a compound according to claim 1, whereby a complex between said compound and copper is formed.

### Claim 19 (depends on 1)

A pharmaceutical composition comprising a pharmaceutically acceptable vehicle and a compound according to claim 1.