D-glycero-B-D-heptose 1-phosphate (HMP) conjugates and use for targeted immune modulation

Patent metadata

Field	Value
Publication number	US-11795190-B2
Application number	US-201816957173-A
Country	US
Kind code	B2
Filing date	Dec 29, 2018
Priority date	Dec 29, 2017
Publication date	Oct 24, 2023
Grant date	Oct 24, 2023

Abstract

Heptose-1-monophosphate-7-derivatives are modifiable immunomodulators that can be used to prepare clinically active conjugate compounds. Such conjugate compounds are useful in modulating an immune response in a subject.

First claim

The invention claimed is:

1. A compound of formula (I):

wherein
Y is H or an atom for forming a salt thereof; and
R is a moiety for conjugating to a functional molecule, and
R is selected from the group consisting of: —C 1-6 alkyl-O—C 1-6 alkyl-NH 2 , —C 1-6 alkyl-NH 2 , —C(O)OH, —C(O)H, —C 0-6 alkyl-C(O)C 0-6 alkyl-NH 2 , and —C 1-6 alkyl-N 3 .

2. The compound of claim 1 , wherein Y is Na or H.

3. The compound of claim 1 , wherein R is selected from the group consisting of: —CH 2 —O—C 2-4 alkyl-NH 2 , —C 1-4 alkyl-NH 2 , —C(O)OH, —C(O)H, —C(O)C 0-3 alkyl-NH 2 , and —C 1-3 alkyl-N 3 .

4. The compound of claim 1 , wherein R is selected from the group consisting of: —CH 2 —O—CH 2 CH 2 -NH 2 , —CH 2 -NH 2 ; —C(O)OH, —C(O)H, —C(O)NH 2 , and —CH 2 N 3 .

5. The compound of claim 1 , selected from the group consisting of:

and the corresponding dihydrogen phosphate thereof.

6. A compound comprising a functional molecule conjugated to a compound of formula (I) as defined in claim 1 , wherein the functional molecule is conjugated via the R group of the compound of formula (I), and wherein the functional molecule is an anti-HIV drug.

7. The compound of claim 6 , wherein the anti-HIV drug is selected from the group consisting of: a Nucleoside/Nucleotide reverse transcriptase inhibitors (NRTI), a Non-nucleoside reverse transcriptase inhibitor (NNRTI), a protease inhibitor (PI), an Entry inhibitor, a Chemokine co-receptor antagonist (CCR5 antagonist), an integrase inhibitor, and a Cytochrome P4503A (CYP3A) inhibitor.

8. The compound of claim 7 , wherein:
the Nucleoside/Nucleotide reverse transcriptase inhibitor (NRTI) is selected from the group consisting of: abacavir (ziagen), emtriacitabine (emtriva), lamivudine (Epivir), zidovudine (Retrovir), didanosine, tenofovir disoproxil fumarate (Viread), and stavudine (Zerit);
the Non-nucleoside reverse transcriptase inhibitor (NNRTI) drug is selected from the group consisting of: rilpivirine (Edurant), etravirine (Intelence), delavirdine mesylate (Rescriptor), efavirenz (Sustiva), and nevirapine;
the protease inhibitor (PI) drug is selected from the group consisting of: tipranavir (Aptivus), indinavir (Crixivan), saquinavir (Invirase), fosamprenavir (Lexiva), ritonavir (Norvir), darunavir (Prezista), atazanavir (Reyataz) and nelfinavir (Viracept);
the entry inhibitor drug is enfuvirtide (Fuzeon);
the integrase inhibitor drug is selected from the group consisting of: raltegravir (Isentress), dolutegravir (Tivicay) and elvitegravir (Vitekta); or
the chemokine co-receptor (CCR5) antagonist is maraviroc (Selzentry).

9. A method for the treatment of HIV comprising administering to a subject an effective amount of the compound of claim 6 .

10. The compound of claim 1 having the following structural formula:

or the corresponding dihydrogen phosphate thereof.

11. The compound of claim 6 having the following structural formula:

or the corresponding dihydrogen phosphate thereof,
wherein X is an anti-HIV drug.

12. A compound selected from the group consisting of:

Assignees

• Nat Res Council Canada
• Governing Council Univ Toronto

Inventors

• Sauvageau Janelle
• Cox Andrew
• Guo Xinyi
• Gray-Owen Scott

Classifications

• A61K39/0011

  Cancer antigens · CPC title

• C07H11/04 Primary

  Phosphates; Phosphites; Polyphosphates · CPC title

• A61K39/002

  Protozoa antigens · CPC title

• A61K39/005

  Trypanosoma antigens · CPC title

• A61K39/008

  Leishmania antigens · CPC title