# US 9,040,488 B2 · Imino sugar derivatives demonstrate potent antiviral activity and reduced toxicity

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- Number: US 9,040,488 B2
- Document ID: US9040488B2
- Status: Granted
- Kind: B2
- Application number: 13/061,734
- Filed: 2009-09-02
- Published: 2011-08-04
- Granted: 2015-05-26
- Earliest claimed: 2008-09-02
- Assignees: Baruch S. Blumberg Institute; Drexel University
- Applicants: Timothy M. Block; Jinhong Chang; Xiaodong Xu
- Inventors: Timothy M. Block; Jinhong Chang; Xiaodong Xu
- Web page: https://patentgrep.com/patent/US9040488B2

## CPC

- A61K 31/47: Quinolines; Isoquinolines
- A61K 31/7056: containing five-membered rings with nitrogen as a ring hetero atom
- C07D 211/46: having a hydrogen atom as the second substituent in position 4
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Imino sugars, such as deoxynojirimycin (DNJ), are glucose analogues that selectively inhibit cellular α-glucosidase I and II (enzymes that process N-linked glycans in glycoprotein) and exhibit broad spectrum antiviral activities against many enveloped viruses. Previously we have reported a novel DNJ derivative, OSL-95II, with antiviral activity and reduced cytotoxicity. In order to develop imino sugars with more potent antiviral activity as well as improved toxicity profile, OSL-95II was modified by diversifying the nitrogen linked alkylated side chain. The antiviral activities were initially tested in bovine viral diarrhea virus (BVDV) infected MDBK cells, yielding several imino sugar derivatives with novel structure and superior antiviral activity and toxicity profile. Furthermore, these new compounds were shown to be active against Dengue virus (DV) and West Nile virus (WNV) infection in BHK cells where potent anti-DV activity having submicromolar EC50 values and SI of greater than 900. These compounds represent a new generation of iminio sugars and their analogues, having application in the clinical treatment of infection of DV and other members of flaviviridae.

## Claims

### Claim 1

A method of inhibiting production of enveloped viruses with a glycosylated envelope in a subject comprising administering a sufficient amount of an anti-viral composition into the subject to contact a mammalian cell infected by said enveloped virus with an effective micromolar amount of the anti-viral composition comprising a 1,5-dideoxy-1,5-imino-D-glucitol derivative selected from the group consisting of PBDNJ-0801-A, PBDNJ-0802-A, PBDNJ-0803-A, PBDNJ-0804-A, PBDNJ-0805-A, PBDNJ-0806-A, PBDNJ-0807-A, and PBDNJ-0808-A and compounds which are pharmaceutically acceptable salts thereof.

### Claim 2 (depends on 1)

The method of claim 1 where the enveloped virus is a flavivirus.

### Claim 3 (depends on 2)

The method of claim 2 where the flavivirus is selected from the group consisting of Dengue, West Nile, Bovine Viral Diaherra virus, Japanese Encephalitis virus, arenaviridae, filoviridae, and bunyaviridase.

### Claim 4 (depends on 3)

The method of claim 3 where an additional antiviral agent is used in combination with said antiviral composition to inhibit production of said enveloped viruses.

### Claim 5 (depends on 4)

The method of claim 4 where the additional antiviral agent is ribavirin.

### Claim 6

A 1,5-dideoxy-1,5-imino-D-glucitol derivative compound having a formula of PBDNJ-0808-A and pharmaceutically acceptable salts thereof.