Bifunctional molecules with antibody-recruiting and entry inhibitory activity against the human immunodeficiency virus

Patent metadata

Field	Value
Publication number	US-10188727-B2
Application number	US-201514883959-A
Country	US
Kind code	B2
Filing date	Oct 15, 2015
Priority date	Oct 13, 2009
Publication date	Jan 29, 2019
Grant date	Jan 29, 2019

Abstract

The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as ARM-H's, function through orthogonal pathways, by inhibiting the gp120-CD4 interaction, and by recruiting anti-DNP antibodies to gp120-expressing cells, thereby preventing cell infection and spread of HIV. It has been shown that ARM-H's bind to gp120 and gp-120 expressing cells competitively with CD4, thereby decreasing viral infectivity as shown by an MT-2 cell assay, the binding leading to formation of a ternary complex by recruiting anti-DNP antibodies to bind thereto, the antibodies present in the ternary complex promoting the complement-dependent destruction of the gp120-expressing cells. Compounds and methods are described herein.

First claim

The invention claimed is:

1. A compound according to the chemical structure:

wherein n is 5 and n′ is 4, or
a pharmaceutically acceptable salt thereof.

2. A pharmaceutical composition comprising an effective amount of a compound according to claim 1 in combination with a pharmaceutically acceptable carrier, additive or excipient.

3. The composition according to claim 2 further comprising an additional anti-HIV agent.

4. The composition according to claim 3 wherein said additional anti-HIV agent is said additional anti-HIV agent is selected from the group consisting of 3TC (Lamivudine), AZT (Zidovudine), (−)-FTC, ddI (Didanosine), ddC (zalcitabine), abacavir (ABC), tenofovir (PMPA), D-D4FC (Reverset), D4T (Stavudine), Racivir, L-FD4C (Elvucitabine), NVP (Nevirapine), DLV (Delavirdine), EFV (Efavirenz), SQVM (Saquinavir mesylate), RTV (Ritonavir), IDV (Indinavir), SQV (Saquinavir), NFV (Nelfinavir), APV (Amprenavir), LPV (Lopinavir), T20 (Enfuvirtide) and mixtures thereof.

5. A method of reducing HIV infected CD cells in a patient comprising administering to an HIV infected patient an effective amount of a composition according to claim 2 .

6. A method of reducing HIV infected CD cells in a patient comprising administering to an HIV infected patient an effective amount of a composition according to claim 3 .

Assignees

• Univ Yale

Inventors

• Spiegel David
• Parker Christopher

Classifications

• C07D405/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• A61K31/4745 Primary

  condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title

• A61K47/545

  Heterocyclic compounds (A61K47/558 takes precedence) · CPC title

• A61K2039/58

  raising an immune response against a target which is not the antigen used for immunisation · CPC title