# US 12,109,269 B2 · Carborane hydroxamic acid matrix metalloproteinase inhibitors and agents for boron neutron capture therapy

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

- Number: US 12,109,269 B2
- Document ID: US12109269B2
- Status: Granted
- Kind: B2
- Application number: 18/175,956
- Filed: 2023-02-28
- Published: 2024-02-15
- Granted: 2024-10-08
- Earliest claimed: 2018-06-29
- Assignees: Loyola University of Chicago
- Applicants: Loyola University of Chicago
- Inventors: Daniel Paul Becker; Marlon Ray Lutz, Jr.
- Web page: https://patentgrep.com/patent/US12109269B2

## CPC

- A61K 31/69: Boron compounds
- A61K 41/0095: {Boron neutron capture therapy, i.e. BNCT, e.g. using boronated porphyrins}
- A61K 47/545: {Heterocyclic compounds (A61K47/558 takes precedence)}
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- C07F 5/05: Cyclic compounds having at least one ring containing boron but no carbon in the ring
- C07F 7/0814: {said ring is substituted at a C ring atom by Si}
- 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
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

Disclosed herein are novel carborane hydroxamic acid matrix metalloproteinase (“MMP”) inhibitors and agents bearing borane-containing moieties and methods for their use in treating or preventing a disease, such as cancer and rheumatoid arthritis. In particular, disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salt thereof: Formula (I) wherein the substituents are as described.

## Claims

### Claim 1

A compound having a structure of Formula (I), or a pharmaceutically acceptable salt thereof:
wherein
m is 1;
n is 1;
W1 and W2 are each absent;
X is aryl;
Y is O or C1-2alkylene-O;
Z is NR1;
R1 is C1-6alkylene-CB; C1-6alkylene-C3-8heteroaryl-C1-6alkylene-CB, CH(C1-3alkylene-C3-8heteroaryl-CB)2, C1-4alkylene-CH(C1-3alkylene-C3-8-heteroaryl-CB)2, CH(C1-3alkylene-C3-8heteroaryl-C1-6alkylene- CB)2, C1-4alkylene-CH(C1-3alkylene-C3-8 heteroaryl-C1-6alkylene-CB)2, C(C1-3alkylene-C3-8-heteroaryl-CB)3, C1-4alkylene- C(C1-3alkylene-C3-8-heteroaryl-CB)3, C(C1-3alkylene-C3-8-heteroaryl-C1-6alkylene-CB)3, or C1-4alkylene-C(C1-3alkylene-C3-8-heteroaryl-C1-6alkylene-CB)3;
R2 is aryl-R4 or C1-2alkylene-aryl-R4;
R3 is H;
R4 is OC1-6alkyl substituted with halo or C1-6alkylene-OC1-6alkyl substituted with halo; and
CB is carborane,
wherein C3-8heteroaryl includes 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S.

### Claim 2 (depends on 1)

The compound or salt of claim 1, wherein X is phenyleneyl.

### Claim 3 (depends on 1)

The compound or salt of claim 1, wherein Y is O.

### Claim 4 (depends on 1)

The compound or salt of claim 1, wherein R1 is C1-6alkylene-CB.

### Claim 5 (depends on 4)

The compound or salt of claim 4, wherein R1 is CH2-CB.

### Claim 6 (depends on 1)

The compound or salt of claim 1, wherein R1 is C1-6alkylene-heteroaryl-C1-6alkylene-CB.

### Claim 7 (depends on 6)

The compound or salt of claim 6, wherein R1 is CH2-heteroaryl-CH2CH2-CB or CH2-heteroaryl-CH2CH2CH2-CB.

### Claim 8 (depends on 1)

The compound or salt of claim 1, wherein R1 is CH(C1-3alkylene-heteroaryl-CB)2, C1-4alkylene-CH(C1-3alkylene-heteroaryl-CB)2, CH(C1-3alkylene-heteroaryl-C1-6alkylene-CB)2, C1-4alkylene-CH(C1-3alkylene-heteroaryl-C1-6alkylene-CB)2, C(C1-3alkylene-heteroaryl-CB)3, C1-4alkylene-C(C1-3alkylene-heteroaryl-CB)3, C(C1-3alkylene-heteroaryl-C1-6alkylene-CB)3, or C1-4alkylene-C(C1-3alkylene-heteroaryl-C1-6alkylene-CB)3.

### Claim 9 (depends on 8)

The compound or salt of claim 8, wherein R1 is CH(CH2-heteroaryl-CB)2 or C(CH2-heteroaryl-CB)3.

### Claim 10 (depends on 8)

The compound or salt of claim 8, wherein heteroaryl is triazolenyl.

### Claim 11 (depends on 1)

The compound or salt of claim 1, wherein R2 is phenylene-R4 or C1-2alkylene-phenylene-R4.

### Claim 12 (depends on 1)

The compound or salt of claim 1, wherein R4 is OC1-6 alkyl substituted with halo.

### Claim 13 (depends on 12)

The compound or salt of claim 12, wherein R4 is OCF3 or OCF2CF3.

### Claim 14 (depends on 13)

The compound or salt of claim 13, wherein R4 is OCF3.

### Claim 15 (depends on 1)

A pharmaceutical formulation comprising the compound or salt of claim 1 and a pharmaceutically acceptable excipient.

### Claim 16 (depends on 1)

A method of inhibiting matrix metalloproteinase (“MMP”) in a cell, comprising contacting the cell with the compound or salt of claim 1, in an amount effective to inhibit MMP.

### Claim 17 (depends on 1)

A method of treating cancer or rheumatoid arthritis in a subject comprising administering to the subject a therapeutically effective amount of a compound of claim 1.

### Claim 18

A tert-butyldimethylsilyl ether propyl azido carborane compound having a structure: