Adamantane derivatives for the treatment of filovirus infection
Inventors
Plewe, Michael Bruno • Brown, Eric • Gantla, Vidyasagar • Henkel, Gregory • McCormack, Kenneth • Sokolova, Nadezda
Assignees
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Publication Number
US-12240857-B2
Publication Date
2025-03-04
Expiration Date
Abstract
Compounds of structural Formula I were developed for the treatment of infections by filoviruses including Ebolavirus and Marburgvirus, wherein, R1, R2, R3, X and Y are defined in the specification.
Core Innovation
The invention is directed to compounds of Structural Formula I and pharmaceutically acceptable salts thereof, with structural variable constraints including X being C-D and Y being a bond, and with D selected from substituent-defined aryl groups or alkyl/alkoxy/carboxylate-derived groups. Additional constraints apply to R1, R2, R3, R8, R9a, R9b, R12, R13, and j, and the disclosed embodiments define the claimed chemical space of Structural Formula I.
The patent also discloses methods of treating infections associated with a Filoviridae enveloped virus, or any virus expressing filovirus glycoproteins to mediate cell entry, by administering to a subject in need thereof a therapeutically effective amount of a compound of Structural Formula I or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable carrier, diluent, or vehicle. The covered viruses include Ebolavirus and Marburgvirus, and dependent refinements include inhibiting the Ebolavirus glycoprotein and adding therapeutic agents such as ribavirin, viral RNA-dependent-RNA polymerase inhibitors, monoclonal antibody therapies, vaccines, small interfering RNAs, microRNAs, and immunomodulators.
The document further includes compound embodiments as a standalone direction to a compound represented by Structural Formula I and selection embodiments from a group of specified compounds. The disclosed examples and supporting content include adamantane-derived amide and carboxamide compounds, spiro-fused and bicyclic cyclic amine motifs, and analytical characterization such as LC/MS and 1H NMR for example compounds.
Claims Coverage
The provided claim set includes independent claims directed to Structural Formula I compounds, methods of treating Filoviridae enveloped virus infections, and selection of compounds from defined groups. Across these claims, the coverage centers on administering therapeutically effective Structural Formula I compounds, or salts, with a pharmaceutically acceptable carrier, and on compound definitions using constrained substituent variables and selected structures. The inventive features number at least four core areas.
Structural Formula I compound definition
A compound represented by Structural Formula I or a pharmaceutically acceptable salt, with X being C-D and Y being a bond, and with D, R1, R2, R3, R8, R9a, R9b, R12, R13, and j defined by the stated selection constraints.
Treating Filoviridae enveloped virus infections with Structural Formula I compounds
A method of treating infections associated with a Filoviridae enveloped virus, or any virus expressing filovirus glycoproteins to mediate cell entry, comprising administering to a subject in need thereof a composition comprising a therapeutically effective amount of a compound of Structural Formula I or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, diluent, or vehicle.
Treating Filoviridae infections using selected compounds in a specified group
A method of treating infections associated with a Filoviridae enveloped virus, or any virus expressing filovirus glycoproteins to mediate cell entry, comprising administering to a subject in need thereof a composition comprising a therapeutically effective amount of a compound selected from a defined group and a pharmaceutically acceptable carrier, diluent, or vehicle.
Selected compound from a defined group
A compound selected from the group consisting of specific compounds, corresponding to structures shown in the accompanying images.
Overall, the independent claims cover Structural Formula I compounds, methods of treating Filoviridae enveloped virus infections using those compounds, and selection-based coverage for specific compounds from defined groups. Dependent refinements further narrow the virus to Ebolavirus or Marburgvirus, specify inhibiting the Ebolavirus glycoprotein, and add therapeutic agent categories and named examples.
Stated Advantages
Inhibiting Filoviridae infection and/or replication associated with filovirus glycoprotein-mediated cell entry.
Provides additional embodiments of Structural Formula I compounds by further constraining substituent variables and enumerating permissible D fragment alternatives.
Documented Applications
Treating infections associated with a Filoviridae enveloped virus, or any virus expressing filovirus glycoproteins to mediate cell entry, by administering a therapeutically effective amount of a compound of Structural Formula I, or a pharmaceutically acceptable salt.
Treating Ebolavirus infection.
Treating Marburgvirus infection.
Inhibiting Ebolavirus glycoprotein as part of the described treatment embodiments.
Co-administration as part of treatment using additional therapeutic agents including ribavirin, viral RNA-dependent-RNA polymerase inhibitors such as favipiravir, triazavirin, and remdesivir, monoclonal antibody therapies including ZMapp, REGN3470-3471-3479, and mAb 114, small interfering RNAs, microRNAs, vaccines including cAd3-EBOZ and rVSV-ZEBOV, and immunomodulators.
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