Substituted phenylpyrrolecarboxamides with therapeutic activity in HIV
Inventors
Debnath, Asim Kumar • Curreli, Francesca • Kwong, Peter D. • Kwon, Young Do
Assignees
New York Blood Center Inc • US Department of Health and Human Services • Government of the United States of America
Publication Number
US-10413527-B2
Publication Date
2019-09-17
Expiration Date
2035-09-18
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Abstract
Substituted phenylpyrrolecarboxamide compounds such as those represented by Formula A can be used in the treatment of HIV infection and related conditions.
Core Innovation
The invention relates to substituted phenylpyrrolecarboxamide compounds represented by Formula A that can be used in the treatment of HIV infection and related conditions. These compounds function as anti-HIV agents, inhibiting infection by targeting the HIV-1 virus.
The problem being addressed is that HIV-1 entry into host cells involves the viral envelope glycoprotein gp120 binding to the host CD4 receptor, followed by binding to a coreceptor CCR5 or CXCR4. There is no current drug available that targets HIV-1 gp120, which is an essential step for viral entry, making this a critical target for therapeutic intervention.
The disclosed compounds act as inhibitors potentially targeting the Phe43 cavity of HIV-1 gp120, thereby interfering with gp120 binding to the host CD4 receptor. The invention also includes pharmaceutical compositions and methods of inhibiting and treating HIV infection by administering these compounds to infected individuals.
Claims Coverage
There is one independent claim which covers a chemical compound represented by Formula 1 with multiple substituent parameters.
Compound represented by Formula 1
A chemical compound represented by Formula 1 featuring a phenylpyrrolecarboxamide core with specific substituents (R4, R5, R6, R7, R8, R13, R14, R15, R15a, and Y) that can be varied as defined in dependent claims. The claim encompasses variants with different halogenations, alkylations, and hydroxymethyl groups at these positions, tailoring anti-HIV activity.
The claim focuses on specific substituted phenylpyrrolecarboxamides, defining variations at multiple positions on the core structure to optimize HIV inhibitory activity and pharmaceutical properties. This provides a chemical space of compounds useful for anti-HIV therapy.
Stated Advantages
The compounds disclosed have antiviral activity against a broad panel of HIV-1 strains including laboratory-adapted and primary isolates.
The compounds target HIV-1 gp120, a novel mechanism for entry inhibition, addressing a currently unmet therapeutic target.
The compounds demonstrate potency in cell-based assays and low cytotoxicity, indicating a favorable therapeutic index.
Documented Applications
Treatment of HIV infection by administering substituted phenylpyrrolecarboxamide compounds that inhibit HIV-1 infection.
Use as entry inhibitors targeting the gp120 binding to CD4 receptor to prevent viral entry and infection propagation.
Pharmaceutical compositions for anti-HIV therapy formulated for various administration routes including oral, parenteral, inhalative, transdermal, and others.
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