Thiophene derivatives as antiviral agents
Inventors
MELDRUM, Eric • de Chassey, Benoit • LINES, LAETITIA • Amaudrut, Jerome • Boubia, Benaissa • DERAIN, VINCENT • Guillier, Fabrice • Montalbetti, Christian • Macleod, Calum • Malagu, Karine Fabienne • VESEY, DAVID ROBERT • WINSHIP, PAUL COLIN MICHAEL
Assignees
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Publication Number
US-11279683-B2
Publication Date
2022-03-22
Expiration Date
Abstract
The present invention relates to a new class of compounds of formula (I) having an antiviral effect and the uses thereof.
Core Innovation
The invention relates to a method of treating a viral infection caused by Influenza virus A by administering, to a subject infected by Influenza virus A, a compound having formula (I), including pharmaceutical salts thereof. The compounds are defined by R1 and R2 forming together a 5-7 membered ring that is saturated or unsaturated, optionally comprising one or more heteroatoms chosen among N, O, and S, with optional substitution patterns for the ring and other radicals.
Formula (I) further defines R3 as a cyclohexyl group substituted in the vicinal position with respect to the CO of the —NH—CO—R3 group by at least one group selected from —C(O)R, —C(O)2R, —C(O)NRR′, —CONHOR, and —CONHSO2R. R4 is a radical selected from ring-containing, aryl, heterocycloalkyl, heteroaryl, and fused variants, optionally substituted by group (B), and R5 is H, (C1-C6)alkyl, (C2-C6)alkenyl, or (C2-C6)alkynyl, or R4 and R5 together form a 5-14 membered ring optionally interrupted by one or several heteroatoms.
The disclosure positions the compound class as antiviral and autophagy-inducing, and also includes thiophene-based antiviral/anticancer compound language in the broader description. The document further describes enumerated example compounds within the formula (I) family and reports IC50 values or potency values for selected compounds, together with autophagy-related marker observations such as LC3 lipidation, p62 expression, LC3 accumulation, p62 downregulation, and mitochondrial effects.
Claims Coverage
The consolidated claim coverage centers on a method of treating Influenza virus A infection by administering a compound of formula (I), with multiple inventive features defined by the R1/R2 ring system and substituent frameworks for R3, R4, and R5, including pharmaceutical salts. Dependent refinements also narrow the target Influenza A subtypes and specify particular structural sub-classes and enumerated example compounds.
Treating Influenza virus A by administering a formula (I) compound
A method of treating a viral infection caused by Influenza virus A comprising administration to a subject infected by Influenza virus A of a compound having formula (I), including pharmaceutical salts thereof.
R1 and R2 forming a 5-7 membered ring
In formula (I), R1 and R2 form together a 5-7 membered ring, saturated or unsaturated, optionally comprising one or more heteroatoms chosen among N, O, and S, and optionally substituted by groups such as (C1-C6)alkyl or (C1-C6)alkyloxy.
R3 cyclohexyl vicinal substitution
R3 represents a cyclohexyl group substituted in the vicinal position with respect to the CO of the —NH—CO—R3 group by at least one group selected from —C(O)R, —C(O)2R, —C(O)NRR′, —CONHOR, and —CONHSO2R.
R4 and R5 substituted radical framework
R4 represents a radical selected from specified ring, aryl, heterocycloalkyl, heteroaryl, fused, and alkyl-linked variants, optionally substituted by group (B), while R5 represents H, (C1-C6)alkyl, (C2-C6)alkenyl, or (C2-C6)alkynyl, and R4 and R5 may together form a 5-14 membered ring optionally interrupted by one or several heteroatoms.
Treatment for specified Influenza A subtypes
The method is further specified for Influenza virus A subtypes selected from H1N1, H1N2, H2N2, H3N1, H3N2, H3N8, H5N1, H5N2, H5N3, H5N8, H5N9, H7N1, H7N2, H7N3, H7N4, H7N7, H7N9, H9N2, and H10N7.
Enumerated cyclohexanecarboxylic acid derivatives and related carboxamide forms
The compound is selected from listed cyclohexanecarboxylic acid derivatives and related carboxamide forms, including named 2-[[3-(arylcarbamoyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl]carbamoyl]cyclohexanecarboxylic acid compounds and related stereoisomer and substituent variants.
Overall, the inventive coverage is directed to treating Influenza virus A infection by administering a formula (I) compound defined by a structured 5-7 membered R1/R2 ring, a vicinally substituted cyclohexyl R3, and defined R4/R5 substitution and ring-forming options, including pharmaceutical salts. Dependent limitations further narrow the Influenza A subtype and the compound sub-classes.
Stated Advantages
The compounds are positioned as antiviral agents.
The compounds are positioned as autophagy-inducing agents.
The compounds are positioned as having antiviral effect for treating Influenza virus A infection.
The compounds are positioned as thiophene-based antiviral/anticancer compounds.
Documented Applications
Treatment of a viral infection caused by Influenza virus A by administration of a compound of formula (I), including pharmaceutical salts thereof.
Treatment of specified Influenza virus A subtypes including H1N1, H1N2, H2N2, H3N1, H3N2, H3N8, H5N1, H5N2, H5N3, H5N8, H5N9, H7N1, H7N2, H7N3, H7N4, H7N7, H7N9, H9N2, and H10N7.
Autophagy-inducing evaluation using LC3 lipidation and p62 expression, with readouts including LC3 positive cytoplasmic puncta, LC3 accumulation, p62 downregulation, and observed mitochondrial effects.
Support for identification and characterization of multiple named compounds via reported NMR and LC/MS readouts.
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