Triazine derivatives and methods of use thereof
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Publication Number
US-12187704-B2
Publication Date
2025-01-07
Expiration Date
Abstract
Certain antiviral compounds, pharmaceutical compositions, and methods related thereto are disclosed.
Core Innovation
The invention relates to Formula I compounds as triazine-derivative antiviral compounds based on a defined scaffold with constrained substituent selections for R1, R2 and/or R10, Rx, Rb, k, Ra, h, X, and Y, and a six-membered N-containing heteroaromatic B ring. The compounds include pharmaceutically acceptable salts, deuterium substitutes, isomers, prodrugs, stereoisomer, tautomer, mixture forms, and other defined forms.
The invention provides Route 1 for preparing Formula (I) compounds and variants, including steps that use an LG leaving group, where LG is defined as Cl, Br, I, or OTf. The disclosure includes a detailed example synthetic sequence that yields specific intermediate compounds and example compounds, including Compound 1 and intermediates identified as 1-C, 1-D, and 1-F, together with characterization and identity information including MS and HNMR data.
The document frames the compounds and pharmaceutical formulations for prevention and treatment of broad viral infections, with emphasis on targeting coronavirus 3C-like protease (3CLpro). The disclosed example series is presented alongside the Route 1 synthetic approach, and the invention further relates to biological performance of the example Formula (I) compounds, including in vitro antiviral potency against SARS-CoV-2 Omicron strains in Calu-3 cells and pharmacokinetic results in rats and in crab-eating monkeys.
Claims Coverage
The independent claim is directed to a defined Formula I compound, including pharmaceutically acceptable salts, deuterium substitutes, isomers, and prodrugs, with multiple constrained structural parameters. Dependent claims cover pharmaceutical composition and therapeutic use contexts, including inhibiting coronavirus 3CLpro and treating virus infection in a subject.
Defined Formula I antiviral compound scaffold with constrained substituents
A compound of Formula I including pharmaceutically acceptable salts, deuterium substitutes, isomers, and prodrugs, wherein R1, R2 or R10 are independently selected from hydrogen, halogen, and deuterium; Rx is selected from hydrogen, deuterium, cyano, alkyl, alkenyl, and alkynyl with optional substitution on the alkyl/alkenyl/alkynyl portion; Rb is selected from hydrogen, deuterium, halogen, and cyano; k=2, 3 or 4; B ring is a six-membered heteroaromatic ring containing N and is substituted with h number of Ra; Ra is selected from hydrogen, deuterium, halogen, haloalkyl and alkyl; h=0, 1 or 2; X is C or N; and Y is selected from alkyl, Cl and Br.
Pharmaceutical composition with pharmaceutically acceptable excipient
A pharmaceutical composition comprising the compound of claim 1, or a pharmaceutically acceptable salt, deuterium substitute, isomer, or prodrug thereof, together with a pharmaceutically acceptable excipient.
Method for inhibiting coronavirus 3CLpro
A method for inhibiting a coronavirus 3C-like protease (3CLpro) by administering an effective amount of the compound of claim 1, or a pharmaceutically acceptable salt, deuterium substitute, isomer, or prodrug thereof.
Method for treating a virus infection in a subject
A method treating a virus infection in a subject by administering an effective amount of the pharmaceutical composition.
Claim coverage centers on a constrained Formula I chemical scaffold, extends to pharmaceutical composition, and includes therapeutic methods for inhibiting coronavirus 3CLpro and treating virus infection in a subject.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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