# US 10,308,607 B2 · Fucosidase inhibitors

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- Number: US 10,308,607 B2
- Document ID: US10308607B2
- Status: Granted
- Kind: B2
- Application number: 15/941,247
- Filed: 2018-03-30
- Published: 2019-03-14
- Granted: 2019-06-04
- Earliest claimed: 2015-07-30
- Assignees: Horizon Orphan LLC
- Applicants: Horizon Orphan LLC
- Inventors: Todd C. Zankel; Sara Louise Isbell; Amanda Anne Ko
- Web page: https://patentgrep.com/patent/US10308607B2

## CPC

- C07D 211/46: having a hydrogen atom as the second substituent in position 4
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 31/445: Non condensed piperidines, e.g. piperocaine
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 17/00: Drugs for dermatological disorders
- A61P 31/12: Antivirals
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 211/74: Oxygen atoms
- 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

The present disclosure relates, in general, to compounds useful as inhibitors of fucosidase enzymes, and to methods and compositions for the treatment of tumors or cancers, such as liver disorders and liver tumors (e.g., hepatocellular carcinoma), with a compound as disclosed herein.

## Claims

### Claim 1

A method for treating a tumor or cancer in a subject in need thereof comprising administering compound II, compound III, or a compound of formula I in a therapeutically effective amount:
wherein:
X1, X2, and X3 are independently selected from the group consisting of OH, halo, and O(C)OCH3;
R is selected from the group consisting of C1-3alkyl and C1-3haloalkyl;
R1 is selected from the group consisting of H, C1-3alkyl, OH, —CO2C1-3alkyl;
R2 is selected from the group consisting of —NRbC(O)Ra, —NRbC(O)ORa, —NRbC(O)NRcRa, —NRbC(O)SRa, —C(O)Ra, and —C(O)NRbRa;
Ra is —C0-3alkylene-G;
G is selected from the group consisting of aryl, heteroaryl, cycloalkyl, and heterocycloalkyl; and
Rb and Rc are independently selected from the group consisting of H and C1-3alkyl, wherein the tumor or cancer is selected from connective tissue cancer, brain cancer, cervical cancer, prostate cancer, or ovarian cancer.

### Claim 2 (depends on 1)

The method of claim 1, wherein the compound reduces tumor metastasis in a subject.

### Claim 3 (depends on 1)

The method of claim 1, wherein the treatment results in a decrease in tumor size in the subject.

### Claim 4 (depends on 1)

The method of claim 1, wherein the treatment results in a reduction of alpha-fetoprotein levels in blood of the subject compared to levels before treatment.

### Claim 5 (depends on 1)

The method of claim 1, wherein the compound is administered intravenously.

### Claim 6 (depends on 5)

The method of claim 5, wherein the compound is administered via the hepatic artery.

### Claim 7 (depends on 1)

The method of claim 1, wherein the compound is administered in combination with a second agent.

### Claim 8 (depends on 7)

The method of claim 7, wherein the second agent is selected from the group consisting of a chemotherapeutic agent, a cytotoxic agent, a radioisotope, an anti-viral agent, an anti-fungal agent, an anti-inflammatory agent and an antibody.

### Claim 9 (depends on 8)

The method of claim 8, wherein the chemotherapeutic agent is selected from the group consisting of doxorubicin and 5-fluorouracil.

### Claim 10 (depends on 8)

The method of claim 8, wherein the second agent is a cytotoxic agent.

### Claim 11 (depends on 10)

The method of claim 10, wherein the cytotoxic agent is selected from the group consisting of mechlorethamine hydrochloride, cyclophosphamide, ifosfamide, chlorambucil, melphalan, busulfan, thiotepa, carmustine, lomustine, dacarbazine and streptozocin.

### Claim 12 (depends on 8)

The method of claim 8, wherein the second agent is a radioisotope.

### Claim 13 (depends on 12)

The method of claim 12, wherein the radioisotope is selected from the group consisting of 131I, 125I, 111In, 90Y, 67Cu, 127Lu, 212Bi, 213Bi, 255Fm, 149Tb, 223Rd, 213Pb, 212Pb, 211At, 89Sr, 153Sm, 166Ho, 225Ac, 186Re, 67Ga, 68Ga and 99mTc.

### Claim 14 (depends on 8)

The method of claim 8, wherein the tumor is associated with hepatitis virus infection, and the second agent is an antiviral agent.