Fucosidase inhibitors

• US 10,308,607 B2
• Filed: 03/30/2018
• Issued: 06/04/2019
• Est. Priority Date: 07/30/2015
• Status: Expired due to Fees

• Current Assignee: Horizon Orphan, LLC (Amgen Inc.)
• Original Assignee: Horizon Orphan, LLC (Amgen Inc.)
• Inventors: Zankel, Todd C., Isbell, Sara Louise, Ko, Amanda Anne
• Primary Examiner(s): Northington Davis, Zinna
• Application Number:
  US15/941,247
• Publication Number:
  US 20190077756A1
• Time in Patent Office: 431 Days
• Field of Search: None
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: 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
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 211/46 having a hydrogen atom as the second substituent in position 4
• CPC Class Codes: C07D 211/74 Oxygen atoms

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

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:

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

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

4. 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.

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

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

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

8. 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.

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

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

11. 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.

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

13. 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.

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