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-10576059-B2
Publication Date
2020-03-03
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
Substituted phenylpyrrolecarboxamide compounds represented by specific chemical formulas are disclosed for use in treating HIV infection and related conditions. These compounds include variations where phenyl, pyrrolyl, or indolyl groups are optionally substituted, and other defined moieties such as R1, A, and B are specified with possible substituents. The compounds may inhibit HIV by targeting and inhibiting gp120 from binding to the host cell receptor CD4, thereby preventing HIV-1 cell entry.
The invention addresses the lack of existing drugs targeting HIV-1 gp120, which is implicated in the initiation of the HIV-1 cell entry process through its interaction with the host cell receptor CD4 and coreceptors CCR5 or CXCR4. Specifically, the Phe43 cavity of HIV-1 gp120 has been identified as a target for developing entry inhibitors, and the compounds disclosed are designed to engage this target.
Claims Coverage
The patent discloses one independent claim directed to a method of treating HIV infection by administering specific compounds represented by chemical formulas. The inventive features focus on structural variations of these compounds that enable their therapeutic use.
Method of treating HIV infection using compounds of Formula 1
Administering to a human infected with HIV a compound represented by Formula 1, wherein the compound includes specific substitutions at R4, R5, R6, R7, R8, R13, R14, R15, R15a, and Y positions as detailed in dependent claims.
Specific substitution patterns to enhance therapeutic effect
Selecting particular substituents such as R4 being hydrogen, R5 being fluorine or hydrogen, R6 being hydrogen, chlorine, methyl, or trifluoromethyl, R7 being fluorine or hydrogen, R13 and R14 being hydrogen or CH2OH, R15 and R15a being hydrogen, and Y being methylene (CH2), to optimize the compound's activity and properties.
Method of treating HIV infection with compounds represented by a selected group of formulas
Administering compounds represented by formulas specified in claim 19, encompassing a group of structurally related substituted phenylpyrrolecarboxamides indicated as having anti-HIV activity.
The independent claims fundamentally cover the therapeutic application of substituted phenylpyrrolecarboxamide compounds characterized by defined substituent patterns for treating HIV infection, focusing on molecular structures that inhibit HIV gp120 interactions.
Stated Advantages
The compounds provide therapeutic activity by inhibiting the HIV-1 gp120 from binding to host cell receptor CD4, targeting an entry step not addressed by existing drugs.
They have demonstrated inhibitory activity against various HIV-1 subtypes and resistant viral strains in multiple assays, showing broad-spectrum anti-HIV efficacy.
The compounds exhibit low cytotoxicity in relevant human cell lines, indicating potential for safe therapeutic use.
Documented Applications
Treatment of HIV infection in humans by administering pharmaceutical compositions comprising substituted phenylpyrrolecarboxamide compounds as inhibitors of HIV-1 gp120-CD4 interaction.
Pharmaceutical compositions for inhibiting HIV infection suitable for various routes of administration including oral, parenteral, intravenous, and topical applications.
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