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 • National Institutes of Health NIH • US Department of Health and Human Services
Publication Number
US-10137107-B2
Publication Date
2018-11-27
Expiration Date
2035-09-18
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
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 specifically target and inhibit HIV-1 gp120 from binding to the host cell receptor CD4. The chemical structures include various substitutions on phenyl, pyrrolyl, and indolyl groups, with different moieties attached to positions designated as R1, A, and B, allowing for a range of compounds with potential antiviral activity.
The problem being addressed is the lack of drugs targeting HIV-1 gp120, which is essential for HIV entry into host cells. HIV-1 gp120 initiates cell entry by binding to the CD4 receptor, triggering conformational changes that enable binding to coreceptors CCR5 or CXCR4. The Phe43 cavity of gp120 is identified as a potential target site for developing entry inhibitors, but prior to this invention, no drugs addressed this target effectively.
The invention provides pharmaceutical compositions comprising these compounds and methods of inhibiting HIV by administering them to infected humans. The compounds can be formulated for various administration routes, including parenteral, oral, transdermal, and others. Detailed chemical descriptions, synthesis methods, and examples of inhibitory activities against various HIV strains and cell types are provided, demonstrating the compounds' potential to inhibit HIV infection through targeting gp120.
Claims Coverage
The patent contains two independent claims covering the chemical compounds and their therapeutic use in HIV treatment. The inventive features include the specific chemical structure of the compounds, their functional substitutions, and the method of treatment using these compounds.
Compounds represented by Formula 1 with specific substitutions
A compound characterized by a structure identified as Formula 1, wherein the variable Y—N(R15, R15a) includes specific groups like —CH2NH2, —CH2CH2NH2, —CH2NHCH3, —CH2N(CH3)2, and others, and other substituents such as R5, R6, R7, R11, R13, R14, and R15 and R15a vary as defined with halides, hydrocarbyls, or carbamimidoyl groups.
Pharmaceutical composition and method of treating HIV infection
A method comprising administering the compound of Formula 1 to a human infected with HIV virus to treat HIV infection, establishing the therapeutic utility of these compounds in inhibiting HIV infection.
Together, these claims cover the novel chemical entities defined by specific substitution patterns on phenylpyrrolecarboxamides and their application in treating HIV infection, emphasizing the invention’s focus on compounds acting on HIV-1 gp120 to inhibit viral entry.
Stated Advantages
The compounds provide a novel means to inhibit HIV-1 gp120 from binding to the host cell receptor CD4, targeting the Phe43 cavity, which was previously unaddressed by existing drugs.
The pharmaceutical compositions can be formulated for multiple administration routes, giving versatility in therapeutic application.
The compounds exhibit effective inhibition of HIV infection in various cell types and against multiple HIV strains, including primary isolates and drug-resistant forms.
Documented Applications
Treatment of HIV infection in humans by administering substituted phenylpyrrolecarboxamide compounds to inhibit viral entry.
Formulation of pharmaceutical compositions including the compounds for various delivery routes such as oral, parenteral, intradermal, subcutaneous, inhalative, transdermal, and transmucosal administration.
Interested in licensing this patent?