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
Publication Number
US-11059808-B2
Publication Date
2021-07-13
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, which can be used in the treatment of HIV infection and related conditions. These compounds are designed as antiviral agents that inhibit HIV-1 infection, particularly by targeting the gp120 envelope glycoprotein of HIV-1.
The problem being addressed is the lack of drugs that target the HIV-1 gp120 protein, which initiates the viral entry process by binding to the host cell receptor CD4 and coreceptors CCR5 or CXCR4. The Phe43 cavity of HIV-1 gp120 has been identified as a potential target for developing entry inhibitors for AIDS therapy and prophylaxis. The invention aims to provide novel compounds that can inhibit HIV-1 entry by interfering with gp120 binding to host receptors.
The compounds disclosed include various embodiments where the phenyl and pyrrole moieties are optionally substituted, and with various substituents at positions R1, A, and B designed to enhance interaction with the target. Methods of inhibiting HIV and treating HIV infection involve administering these compounds to humans infected with HIV. The detailed description includes the structural features, synthetic methods, and pharmaceutical compositions for these compounds.
Claims Coverage
The patent includes eight claims, with independent claims focusing on the compound structure, composition, and methods of treating HIV infection. Five main inventive features are identified from these claims.
Compound represented by Formula 1
A compound having a structure represented by Formula 1, which encompasses substituted phenylpyrrolecarboxamide derivatives with specific functional groups and substitution patterns designed to inhibit HIV.
Composition comprising the compound
A pharmaceutical composition comprising a compound according to Formula 1, optionally including at least one pharmaceutically acceptable carrier suitable for treatment of HIV infection.
Method of inhibiting HIV by administering the compound
A method for inhibiting HIV infection by administering to a human being infected with HIV a compound according to Formula 1.
Method of treating HIV infection by administering the compound
A method for treating HIV infection by administering a compound represented by Formula 1 to an HIV-infected human being.
Specific compound substitutions enhancing activity
Compounds wherein substitutions such as R5 being fluorine (F), R6 being chlorine (Cl), and R14 being methyl (CH3) are specified to enhance the antiviral properties of the compounds.
The claims cover the novel substituted phenylpyrrolecarboxamide compounds structurally defined in Formula 1, their pharmaceutical compositions, and therapeutic methods for HIV treatment, including specific advantageous substitutions to optimize efficacy.
Stated Advantages
The compounds target the HIV-1 gp120 protein, for which no drugs were previously available, providing a new mechanism for inhibiting viral entry.
The compounds show broad-spectrum anti-HIV activity against multiple HIV-1 subtypes and strains, including lab-adapted and primary isolates.
Pharmaceutical compositions can be formulated for various routes of administration, enhancing therapeutic flexibility.
Documented Applications
Treatment of HIV infection and related conditions in humans by administering substituted phenylpyrrolecarboxamide compounds.
Use of compounds for inhibiting HIV-1 entry by targeting the gp120 envelope glycoprotein.
Formulation of the compounds into pharmaceutical compositions suitable for oral, parenteral, intravenous, intradermal, subcutaneous, inhalative, transdermal, topical, transmucosal, rectal, intravaginal, intraperitoneal, buccal, and intraocular administration.
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