Anti-HCMV compositions and methods
Inventors
Remiszewski, Stacy • Koyuncu, Emre • Sun, Qun • Chiang, Lillian
Assignees
Forge Life Science LLC • Evrys Bio LLC
Publication Number
US-10723708-B2
Publication Date
2020-07-28
Expiration Date
2035-11-09
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Abstract
This document relates to compounds useful as agents for preventing or treating human cytomegalovirus (HCMV) infections.
Core Innovation
This invention provides compounds useful as agents for preventing or treating human cytomegalovirus (HCMV) infections. The compounds are described by a specific chemical structure, referred to as Formula I, with defined substituents and configurations. Methods for treating or preventing HCMV infection involve administering a therapeutically effective amount of one or more of these compounds to a subject.
The invention addresses the problem of HCMV being a major cause of birth defects and opportunistic infections in immunosuppressed individuals, particularly organ transplant patients who are at high risk for viral infections. Available HCMV antivirals suffer from nephrotoxic side effects and increasing rates of drug-resistance, which significantly reduce graft and patient survival. HCMV-mediated immune modulation can also reactivate other latent viruses in adults.
The compounds of the invention can inhibit HCMV production in cells infected by the virus. Methods include contacting an HCMV-infected cell with a virus production inhibiting amount of the compounds, as well as administering the compounds in various pharmaceutical preparations and delivery routes. The compounds may also be used in conjunction with other antiviral agents.
Claims Coverage
There are two independent claims in this patent: one to a composition and one to a pharmaceutical composition, both covering core inventive features.
Composition comprising compounds of Formula I
A composition comprising a compound of Formula I: - X is NH or O, provided that when m is 1, X is NH. - R1 and R2 are independently selected from H, halo, lower straight chain alkyl, lower branched alkyl, and OR6. - R3, R4, and R5 are independently selected from H, halo, —CN, lower straight chain alkyl, lower branched alkyl, and OR6. - Each R6 is independently selected from H, lower straight chain alkyl, and lower branched alkyl. - m is 0 or 1. - n is 0, 1, 2 or 3, provided that when m is 1, n is not 3. - Ar is a bicyclic aryl group having between 8 and 12 ring atoms, with 0, 1 or 2 heteroatoms (N, O, S), and substituted with 0, 1 or 2 groups (halo, —CN, lower straight chain alkyl, lower branched alkyl). - Includes pharmaceutically acceptable salts thereof.
Pharmaceutical composition comprising compounds of Formula I
A pharmaceutical composition comprising a compound of Formula I as specified above, and a pharmaceutically acceptable carrier. - Formulation suitable for administration (e.g., parenteral, oral, topical, rectal). - Compound is as defined for the composition claim with allowed subsituents and variations. - Includes pharmaceutically acceptable salts thereof.
The inventive features cover compositions and pharmaceutical compositions comprising compounds with a defined structure (Formula I) and specified variants, intended for use against HCMV infection.
Stated Advantages
The compounds are useful for treating and/or preventing HCMV infections.
The compounds can inhibit HCMV production in a cell infected with the virus.
Documented Applications
Prevention of human cytomegalovirus (HCMV) infection in subjects.
Treatment of human cytomegalovirus (HCMV) infection in subjects.
Inhibition of HCMV production in infected cells.
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