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-10869856-B2
Publication Date
2020-12-22
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 discloses substituted phenylpyrrolecarboxamide compounds represented by Formula A that are useful in the treatment of HIV infection and related conditions. These anti-HIV compounds can be formulated into pharmaceutical compositions and administered to humans infected with HIV to inhibit the virus.
The background identifies that HIV-1 infects host cells via its envelope glycoprotein gp120 binding to the host cell receptor CD4, triggering conformational changes that enable binding to coreceptors CCR5 or CXCR4. Notably, there is no existing drug that targets HIV-1 gp120. The gp120 Phe43 cavity is identified as a potential therapeutic target for developing entry inhibitors to treat or prevent AIDS.
The invention addresses this problem by providing compounds that may target and inhibit gp120 from binding to the CD4 receptor on host cells. The disclosed compounds have defined chemical structures with various substituents detailed in Formula A and its embodiments. Methods of use include administering these compounds to humans infected with HIV to inhibit viral entry and treat the infection.
Claims Coverage
The patent includes one independent claim directed to a compound represented by a specific chemical formula and several dependent claims refining structural features. The inventive features primarily relate to the structural characteristics of the claimed compounds and their substituents.
Chemical structure of substituted phenylpyrrolecarboxamide compound
A compound represented by Formula 1 with defined substituents, including specific groups at positions R4, R5, R6, R7, R8, R9, R10, R11, R13, R14, R15, R15a, R16 and a hydrocarbyl Y group of C1-3 length.
Specific substituent selections at key positions
Selections of R11, R15, and R15a as independently H, C1-6 alkyl, carbamimidoyl, C1-6 aryl, or C1-6 heteroaryl; R4, R5, R7, and R8 from groups including H, F, Cl, NH2, CH3, SO2NH2, OCH3, CH2OH, or N(C2H5)2; R6 as H, F, Cl, CN, CH3, CF3, OH, NH2, C1-6 alkyl or C1-6 alkoxy; R9, R10, and R11 independently H or CH3; R13 and R14 independently H, F, Cl, NH2, CH3, SO2NH2, OCH3, CH2OH, or N(C2H5)2; R15 and R15a independently as aforementioned; R16 as H or CH3; Y as C1-3 hydrocarbyl.
Preferred stereoisomerism and defined chemical structures
Claims specify compounds having stereochemistry consisting of one stereoisomer and specific structures as illustrated for embodiments of Formula 1.
The claims cover substituted phenylpyrrolecarboxamide compounds with precise substituent groups and stereochemistry, enabling targeted inhibition of HIV through molecular structures designed for therapeutic efficacy.
Stated Advantages
The compounds disclosed can target and inhibit HIV-1 gp120 binding to the CD4 receptor, addressing a previously untargeted mechanism in HIV therapy.
Pharmaceutical compositions comprising these compounds can be formulated for various administration routes with appropriate excipients, offering flexibility in clinical use.
Compounds exhibit inhibitory activity against a wide range of HIV-1 strains, including laboratory-adapted and primary isolates, as demonstrated by in vitro assays.
Compounds show selective antiviral activity with acceptable cytotoxicity profiles in multiple cell types, indicating potential therapeutic use.
Documented Applications
Treatment and prevention of HIV infection in humans by administering the substituted phenylpyrrolecarboxamide compounds.
Use of the compounds as entry inhibitors targeting HIV-1 gp120 to prevent viral entry into host cells.
Pharmaceutical compositions for administration via various routes including oral, parenteral, intravenous, intradermal, subcutaneous, inhalative, transdermal, topical, transmucosal, rectal, intravaginal, intraperitoneal, buccal, and intraocular.
Interested in licensing this patent?