RU2023133687A

RU2023133687A - N4-HYDROXYCYTIDINE AND DERIVATIVES AND RELATED ANTIVIRAL USES

Info

Publication number: RU2023133687A
Application number: RU2023133687A
Authority: RU
Inventors: Джордж Р. ПЕЙНТЕР; Грегори Р. БЛЮМЛИНГ; Майкл Дж. НАТЧЕС; Дэвид Гетри
Original assignee: Эмори Юниверсити
Priority date: 2017-12-07
Filing date: 2018-12-07
Publication date: 2024-01-10

Claims

1. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula I

Формула IFormula I

or its pharmaceutical or physiological salt,

where X is CH ₂ , CHCH ₃ , C(CH ₃ ) ₂ , CHF, CF ₂ or CD ₂ ;

Y represents N or CR';

Z represents N or CR";

R' is hydrogen, deuterium, halogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or carbonyl, wherein R' is optionally substituted with one or more of the same or different R ¹⁰ ;

R" is hydrogen, deuterium, halogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl, hydroxyl, thiol or carbonyl, wherein R' is optionally substituted with one or more of the same or various R ¹⁰ ;

R ¹ , R ² , R ³ and R ⁵ are each independently selected from H, optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonate, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyl, optionally substituted oxymethoxythiocarbonyl, optionally substituted oxymethylcarbonyl, optionally substituted oxymethylthiocarbonyl, L-amino acid esters, ester s D-amino acids, N- esters substituted L-amino acids, N, N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N, N-disubstituted D-amino acid esters, optionally substituted sulfenyl, optionally substituted imidate, optionally substituted hydrazonate, optionally substituted oxymyl, optionally substituted imidinyl, optionally substituted imidyl, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carbonimidate, optionally substituted thiocarbonimidate, optionally substituted carbonimidyl, optionally substituted carbamimidate , optionally substituted carbamimidyl, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis(acyloxybenzyl)esters, optionally substituted (acyloxybenzyl)esters and BAB esters, wherein ^R1 , ^R2 , ^R3 and ^R5 are optionally substituted by one or more same or different R ¹⁰ ;

R ¹⁰ represents deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocycloxy, heterocarbocycloxy, aryloxy, heteroaryloxy, heterocycloxy, cycloalkoxy, cycloalkenoxy, alkylamino, (alkyl) ₂ amino, carbocyclamino, heterocarbocyclamino, arylamino, heteroarylamino, heterocyclamino, cycloalkamino, cycloalkenamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R ¹⁰ is optionally substituted with one or more of the same or different R ¹¹ ;

R ¹¹ represents deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocycloxy, heterocarbocycloxy, aryloxy, heteroaryloxy, heterocycloxy, cycloalkoxy, cycloalkenoxy, alkylamino, (alkyl) ₂ amino, carbocyclamino, heterocarbocyclamino, arylamino, heteroarylamino, heterocyclamino, cycloalkamino, cycloalkenamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl; And

the lipid is a C11-C22 higher alkyl, C11-C22 higher alkoxy, polyethylene glycol or aryl substituted with an alkyl group, or a lipid as described herein.

2. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula II

Формула IIFormula II

or a pharmaceutical or physiological salt thereof, where

X is CH ₂ , CHCH ₃ , C(CH ₃ ) ₂ , CHF, CF ₂ or CD ₂ ;

Y represents N or CR';

Z represents N or CR";

R' is deuterium, halogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or carbonyl, wherein R' is optionally substituted with one or more of the same or different R ¹⁰ ;

with the proviso that not all R ¹ , R ² , R ³ and R ⁵ are H;

3. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula III

Формула IIIFormula III

or its pharmaceutical or physiological salt,

where X represents CH ₂ , CHCH ₃ , C(CH ₃ ) ₂ , CHF, CF ₂ or CD ₂ ;

Z represents N or CR";

R" is deuterium, halogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl, hydroxyl, thiol or carbonyl, wherein R' is optionally substituted with one or more of the same or different R ¹⁰ ;

R ¹ , R ² , R ³ and R ⁵ are each independently selected from H, optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonate, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyl, optionally substituted oxymethoxythiocarbonyl, optionally substituted oxymethylcarbonyl, optionally substituted oxymethylthiocarbonyl, L-amino acid esters, esters s D-amino acids, N- esters substituted L-amino acids, N, N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N, N-disubstituted D-amino acid esters, optionally substituted sulfenyl, optionally substituted imidate, optionally substituted hydrazonate, optionally substituted oxymyl, optionally substituted imidinyl, optionally substituted imidyl, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carbonimidate, optionally substituted thiocarbonimidate, optionally substituted carbonimidyl, optionally substituted carbamimidate , optionally substituted carbamimidyl, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis(acyloxybenzyl)esters, optionally substituted (acyloxybenzyl)esters and BAB esters, wherein ^R1 , ^R2 , ^R3 and ^R5 are optionally substituted by one or more same or different R ¹⁰ ;

with the proviso that not all R ¹ , R ² , R ³ and R ⁵ are H;

4. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula IV

Формула IVFormula IV

or its pharmaceutical or physiological salt,

where X is CHCH ₃ , C(CH ₃ ) ₂ , CHF, CF ₂ or CD ₂ ;

with the proviso that not all R ¹ , R ² , R ³ and R ⁵ are H;

5. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula V

Формула VFormula V

or its pharmaceutical or physiological salt,

wherein R ¹ , R ² , R ³ and R ⁵ are each independently selected from the following: optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters , optionally substituted thiocarbonates, optionally substituted S-thiocarbonate, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyl, optionally substituted oxymethoxythiocarbonyl, optionally substituted oxymethylcarbonyl, optionally substituted oxymethylthiocarbonyl, L-amino acid esters, D-amino acid esters, N esters -substituted L-amino acids, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally substituted sulfenyl, optionally substituted imidate, optionally substituted hydrazonate, optional substituted oxymyl, optionally substituted imidinyl, optionally substituted imidyl, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carbonimidate, optionally substituted thiocarbonimidate, optionally substituted carbonimidyl, optionally substituted carb amididate, optionally substituted carbamimidyl, optionally substituted thioacetal , optionally substituted S-acyl-2-thioethyl, optionally substituted bis(acyloxybenzyl)esters, optionally substituted (acyloxybenzyl)esters and BAB esters, wherein R ¹ , R ² , R ³ and R ⁵ are optionally substituted with one or more identical or different R ¹⁰ ;

6. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula VI

Формула VIFormula VI

or its pharmaceutical or physiological salt,

wherein R ¹ , R ² and R ³ are each independently selected from the following: optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonate, optionally substituted dithiocarbonates , optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyl, optionally substituted oxymethoxythiocarbonyl, optionally substituted oxymethylcarbonyl, optionally substituted oxymethylthiocarbonyl, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N, N-disubstituted L esters -amino acids, N-substituted D-amino acid esters, N, N-disubstituted D-amino acid esters, optionally substituted sulfenyl, optionally substituted imidate, optionally substituted hydrazonate, optionally substituted oxymyl, optionally substituted imidinyl, optionally substituted imidyl, optionally substituted aminal , optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carbonimidate, optionally substituted thiocarbonimidate, optionally substituted carbonimidyl, optionally substituted carbamimidyl, optionally substituted carbamimidyl, optionally substituted thioacetal, optionally substituted ny S-acyl-2-thioethyl, optionally substituted complex bis-(acyloxybenzyl)esters, optionally substituted (acyloxybenzyl)esters and BAB-esters, wherein R ¹ , R ² and R ³ are optionally substituted with one or more of the same or different R ¹⁰ ;

7. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula VIa-f

or its pharmaceutical or physiological salt,

8. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula VII

Формула VIIFormula VII

or a pharmaceutical or physiological salt thereof, where

R ¹ , R ² and R ⁵ are each independently selected from the following: optionally substituted esters, optionally substituted branched-chain esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched-chain thioesters, optionally substituted thiocarbonates , optionally substituted S-thiocarbonate, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyl, optionally substituted oxymethoxythiocarbonyl, optionally substituted oxymethylcarbonyl, optionally substituted oxymethylthiocarbonyl, L-amino acid esters, D-amino acid esters, esters N-substituted L- amino acids, N, N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N, N-disubstituted D-amino acid esters, optionally substituted sulfenyl, optionally substituted imidate, optionally substituted hydrazonate, optionally substituted oxymyl, optional substituted imidinyl, optionally substituted imidyl, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carbonimidate, optionally substituted thiocarbonimidate, optionally substituted carbonimidyl, optionally substituted carbamimidate, optionally substituted carbamimidyl, optionally substituted thioacetal, optionally substituted S -acyl-2-thioethyl, optionally substituted bis(acyloxybenzyl)esters, optionally substituted (acyloxybenzyl)esters and BAB esters, wherein R ¹ , R ² and R ⁵ are optionally substituted with one or more of the same or different R ¹⁰ ;

9. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula VIII

Формула VIIIFormula VIII

or its pharmaceutical or physiological salt,

wherein R ¹ , R ³ and R ⁵ are each independently selected from the following: optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonate, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyl, optionally substituted oxymethoxythiocarbonyl, optionally substituted oxymethylcarbonyl, optionally substituted oxymethylthiocarbonyl, L-amino acid esters, D-amino acid esters from, N-substituted esters L -amino acids, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally substituted sulfenyl, optionally substituted imidate, optionally substituted hydrazonate, optionally substituted oxymyl, optionally substituted imidinyl, optionally substituted imidyl, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carbonimidate, optionally substituted thiocarbonimidate, optionally substituted carbonimidyl, optionally substituted carbamimidate, optionally substituted pure carbamimidyl, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis(acyloxybenzyl)esters, optionally substituted (acyloxybenzyl)esters and BAB esters, wherein R ¹ , R 3 and R ⁵ are optionally substituted with one or more of the same or different R ¹⁰ ;

10. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula IX

Формула IXFormula IX

or its pharmaceutical or physiological salt,

wherein R ² , R ³ and R ⁵ are each independently selected from the following: optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonate, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyl, optionally substituted oxymethoxythiocarbonyl, optionally substituted oxymethylcarbonyl, optionally substituted oxymethylthiocarbonyl, L-amino acid esters, D-amino acid esters from, N-substituted esters L -amino acids, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally substituted sulfenyl, optionally substituted imidate, optionally substituted hydrazonate, optionally substituted oxymyl, optionally substituted imidinyl, optionally substituted imidyl, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carbonimidate, optionally substituted thiocarbonimidate, optionally substituted carbonimidyl, optionally substituted carbamimidate, optionally substituted pure carbamimidyl, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis(acyloxybenzyl)esters, optionally substituted (acyloxybenzyl)esters and BAB esters, wherein ^R2 , ^R3 and ^R5 are optionally substituted by one or more of the same or different ^R10 ;

11. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula X

Формула XFormula X

or its pharmaceutical or physiological salt,

wherein R ¹ and R ⁵ are each independently selected from the following: optionally substituted esters, optionally substituted branched-chain esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched-chain thioesters, optionally substituted thiocarbonates, optional substituted S-thiocarbonate, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyl, optionally substituted oxymethoxythiocarbonyl, optionally substituted oxymethylcarbonyl, optionally substituted oxymethylthiocarbonyl, L-amino acid esters, D-amino acid esters, N-substitute esters natural L-amino acids, N, N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N, N-disubstituted D-amino acid esters, optionally substituted sulfenyl, optionally substituted imidate, optionally substituted hydrazonate, optionally substituted oxymyl, optionally substituted imidinyl , optionally substituted imidyl, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carbonimidate, optionally substituted thiocarbonimidate, optionally substituted carbonimidyl, optionally substituted carbamimidyl, optionally substituted carbamimidyl , optionally substituted thioacetal, optionally substituted S-acyl -2-thioethyl, optionally substituted bis(acyloxybenzyl)esters, optionally substituted (acyloxybenzyl)esters and BAB esters, wherein R ¹ and R ⁵ are optionally substituted with one or more of the same or different R ¹⁰ ;

12. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula XI

Формула XIFormula XI

or its pharmaceutical or physiological salt,

wherein R ¹ and R ³ are each independently selected from the following: optionally substituted esters, optionally substituted branched-chain esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched-chain thioesters, optionally substituted thiocarbonates, optional substituted S-thiocarbonate, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyl, optionally substituted oxymethoxythiocarbonyl, optionally substituted oxymethylcarbonyl, optionally substituted oxymethylthiocarbonyl, L-amino acid esters, D-amino acid esters, N-substitute esters natural L-amino acids, N, N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N, N-disubstituted D-amino acid esters, optionally substituted sulfenyl, optionally substituted imidate, optionally substituted hydrazonate, optionally substituted oxymyl, optionally substituted imidinyl , optionally substituted imidyl, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carbonimidate, optionally substituted thiocarbonimidate, optionally substituted carbonimidyl, optionally substituted carbamimidyl, optionally substituted carbamimidyl , optionally substituted thioacetal, optionally substituted S-acyl -2-thioethyl, optionally substituted bis(acyloxybenzyl)esters, optionally substituted (acyloxybenzyl)esters and BAB esters, wherein R ¹ and R ³ are optionally substituted with one or more of the same or different R ¹⁰ ;

13. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula XII

Формула XIIFormula XII

or its pharmaceutical or physiological salt,

wherein R ¹ and R ² are each independently selected from the following: optionally substituted esters, optionally substituted branched-chain esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched-chain thioesters, optionally substituted thiocarbonates, optional substituted S-thiocarbonate, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyl, optionally substituted oxymethoxythiocarbonyl, optionally substituted oxymethylcarbonyl, optionally substituted oxymethylthiocarbonyl, L-amino acid esters, D-amino acid esters, N-substitute esters natural L-amino acids, N, N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N, N-disubstituted D-amino acid esters, optionally substituted sulfenyl, optionally substituted imidate, optionally substituted hydrazonate, optionally substituted oxymyl, optionally substituted imidinyl , optionally substituted imidyl, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carbonimidate, optionally substituted thiocarbonimidate, optionally substituted carbonimidyl, optionally substituted carbamimidyl, optionally substituted carbamimidyl , optionally substituted thioacetal, optionally substituted S-acyl -2-thioethyl, optionally substituted bis(acyloxybenzyl)esters, optionally substituted (acyloxybenzyl)esters and BAB esters, wherein R ¹ and R ² are optionally substituted with one or more of the same or different R ¹⁰ ;

14. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula XIII

Формула XIIIFormula XIII

or its pharmaceutical or physiological salt,

wherein R ² and R ⁵ are each independently selected from the following: optionally substituted esters, optionally substituted branched-chain esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched-chain thioesters, optionally substituted thiocarbonates, optional substituted S-thiocarbonate, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyl, optionally substituted oxymethoxythiocarbonyl, optionally substituted oxymethylcarbonyl, optionally substituted oxymethylthiocarbonyl, L-amino acid esters, D-amino acid esters, N-substitute esters natural L-amino acids, N, N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N, N-disubstituted D-amino acid esters, optionally substituted sulfenyl, optionally substituted imidate, optionally substituted hydrazonate, optionally substituted oxymyl, optionally substituted imidinyl , optionally substituted imidyl, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carbonimidate, optionally substituted thiocarbonimidate, optionally substituted carbonimidyl, optionally substituted carbamimidyl, optionally substituted carbamimidyl , optionally substituted thioacetal, optionally substituted S-acyl -2-thioethyl, optionally substituted bis(acyloxybenzyl)esters, optionally substituted (acyloxybenzyl)esters and BAB esters, wherein R ² and R ⁵ are optionally substituted with one or more of the same or different R ¹⁰ ;

15. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula XIV

Формула XIVFormula XIV

or its pharmaceutical or physiological salt,

wherein R ² and R ³ are each independently selected from the following: optionally substituted esters, optionally substituted branched-chain esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched-chain thioesters, optionally substituted thiocarbonates, optional substituted S-thiocarbonate, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyl, optionally substituted oxymethoxythiocarbonyl, optionally substituted oxymethylcarbonyl, optionally substituted oxymethylthiocarbonyl, L-amino acid esters, D-amino acid esters, N-substitute esters natural L-amino acids, N, N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N, N-disubstituted D-amino acid esters, optionally substituted sulfenyl, optionally substituted imidate, optionally substituted hydrazonate, optionally substituted oxymyl, optionally substituted imidinyl , optionally substituted imidyl, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carbonimidate, optionally substituted thiocarbonimidate, optionally substituted carbonimidyl, optionally substituted carbamimidyl, optionally substituted carbamimidyl , optionally substituted thioacetal, optionally substituted S-acyl -2-thioethyl, optionally substituted bis(acyloxybenzyl)esters, optionally substituted (acyloxybenzyl)esters and BAB esters, wherein R ² and R ³ are optionally substituted with one or more of the same or different R ¹⁰ ;

16. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula XV

Формула XVFormula XV

or its pharmaceutical or physiological salt,

wherein R ³ and R ⁵ are each independently selected from the following: optionally substituted esters, optionally substituted branched-chain esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched-chain thioesters, optionally substituted thiocarbonates, optional substituted S-thiocarbonate, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyl, optionally substituted oxymethoxythiocarbonyl, optionally substituted oxymethylcarbonyl, optionally substituted oxymethylthiocarbonyl, L-amino acid esters, D-amino acid esters, N-substitute esters natural L-amino acids, N, N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N, N-disubstituted D-amino acid esters, optionally substituted sulfenyl, optionally substituted imidate, optionally substituted hydrazonate, optionally substituted oxymyl, optionally substituted imidinyl , optionally substituted imidyl, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carbonimidate, optionally substituted thiocarbonimidate, optionally substituted carbonimidyl, optionally substituted carbamimidyl, optionally substituted carbamimidyl , optionally substituted thioacetal, optionally substituted S-acyl -2-thioethyl, optionally substituted bis(acyloxybenzyl)esters, optionally substituted (acyloxybenzyl)esters and BAB esters, wherein R ³ and R ⁵ are optionally substituted with one or more of the same or different R ¹⁰ ;

17. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula XVI

Формула XVIFormula XVI

or its pharmaceutical or physiological salt,

wherein R ² is selected from the following: optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonate, optionally substituted dithiocar bonates , optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyl, optionally substituted oxymethoxythiocarbonyl, optionally substituted oxymethylcarbonyl, optionally substituted oxymethylthiocarbonyl, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N, N-disubstituted L esters -amino acids, N-substituted D-amino acid esters, N, N-disubstituted D-amino acid esters, optionally substituted sulfenyl, optionally substituted imidate, optionally substituted hydrazonate, optionally substituted oxymyl, optionally substituted imidinyl, optionally substituted imidyl, optionally substituted aminal , optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carbonimidate, optionally substituted thiocarbonimidate, optionally substituted carbonimidyl, optionally substituted carbamimidyl, optionally substituted carbamimidyl, optionally substituted thioacetal, optionally substituted ny S-acyl-2-thioethyl, optionally substituted complex bis-(acyloxybenzyl)esters, optionally substituted (acyloxybenzyl)esters and BAB-esters, wherein R ² is optionally substituted with one or more of the same or different R ¹⁰ ;

18. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula XVII

Формула XVIIFormula XVII

or its pharmaceutical or physiological salt,

wherein R ³ is selected from the following: optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonate, optionally substituted dithiocar bonates , optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyl, optionally substituted oxymethoxythiocarbonyl, optionally substituted oxymethylcarbonyl, optionally substituted oxymethylthiocarbonyl, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N, N-disubstituted L esters -amino acids, N-substituted D-amino acid esters, N, N-disubstituted D-amino acid esters, optionally substituted sulfenyl, optionally substituted imidate, optionally substituted hydrazonate, optionally substituted oxymyl, optionally substituted imidinyl, optionally substituted imidyl, optionally substituted aminal , optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carbonimidate, optionally substituted thiocarbonimidate, optionally substituted carbonimidyl, optionally substituted carbamimidyl, optionally substituted carbamimidyl, optionally substituted thioacetal, optionally substituted ny S-acyl-2-thioethyl, optionally substituted complex bis-(acyloxybenzyl)esters, optionally substituted (acyloxybenzyl)esters and BAB-esters, wherein R ³ is optionally substituted with one or more of the same or different R ¹⁰ ;

19. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula XVIII

Формула XVIIIFormula XVIII

or its pharmaceutical or physiological salt,

wherein R ¹ is selected from the following: optionally substituted branched esters, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonate, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyl, optionally substituted oxymethoxythiocarbonyl, optionally substituted hydroxymethylcarbonyl, optionally substituted hydroxymethylthiocarbonyl, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N, N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, esters esters of N, N-disubstituted D-amino acids, optionally substituted sulfenyl, optionally substituted imidate, optionally substituted hydrazonate, optionally substituted oxymyl, optionally substituted imidinyl, optionally substituted imidyl, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemi acetal, optionally substituted carbonimidate, optionally substituted thiocarbonimidate, optionally substituted carbonimidyl, optionally substituted carbamimidate, optionally substituted carbamimidyl, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis(acyloxybenzyl)esters, optionally substituted pure complex (acyloxybenzyl) esters and BAB esters, wherein R ¹ is optionally substituted with one or more identical or different R ¹⁰ ;

20. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of Formula XIX

Формула XIXFormula XIX

or its pharmaceutical or physiological salt,

wherein R ⁵ is selected from the following: optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonate, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyl, optionally substituted oxymethoxythiocarbonyl , optionally substituted oxymethylcarbonyl, optionally substituted oxymethylthiocarbonyl, esters of L-amino acids, esters of D-amino acids, esters of N-substituted L-amino acids, esters of N, N-disubstituted L-amino acids, esters of N-substituted D-amino acids, esters of N, N-disubstituted D-amino acids, optionally substituted sulfenyl, optionally substituted imidate, optionally substituted hydrazonate, optionally substituted oxymyl, optionally substituted imidinyl, optionally substituted imidyl, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carbonimidate, optionally substituted thiocarbonimidate, optionally substituted carbonimidyl, optionally substituted carbamimidate, optionally substituted carbamimidyl, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis(acyloxybenzyl)esters, optionally substituted (acyloxybenzyl)esters and BABs -esters wherein R ⁵ is optionally substituted with one or more identical or different R ¹⁰ ;

21. Pharmaceutical composition according to claim 1, characterized in that R ¹ , R ² , R ³ and R ⁵ are each independently selected from H,

, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ;

Y ¹ represents O or S;

Y ³ represents OH or BH ₃ ^- M ⁺ ;

R ⁶ represents hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocycloxy, heterocarbocycloxy, aryloxy, heteroaryloxy, heterocycloxy, cycloalkoxy, cycloalkenoxy, alkylamino, (alkyl) ₂ amino, carbocyclamino, heterocarbocyclamino, arylamino, heteroarylamino, heterocyclamino, cycloalkamino, cycloalkenamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, cyano or lipid, wherein R ⁶ is optionally substituted with one or more of the same or different R ¹⁰ ;

R ⁷ represents deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocycloxy, heterocarbocycloxy, aryloxy, heteroaryloxy, heterocycloxy, cycloalkoxy, cycloalkenoxy, alkylamino, (alkyl) ₂ amino, carbocyclamino, heterocarbocyclamino, arylamino, heteroarylamino, heterocyclamino, cycloalkamino, cycloalkenamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R ⁷ is optionally substituted with one or more of the same or different R ¹⁰ ;

R ⁸ represents deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocycloxy, heterocarbocycloxy, aryloxy, heteroaryloxy, heterocycloxy, cycloalkoxy, cycloalkenoxy, alkylamino, (alkyl) ₂ amino, carbocyclamino, heterocarbocyclamino, arylamino, heteroarylamino, heterocyclamino, cycloalkamino, cycloalkenamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R ⁸ is optionally substituted with one or more of the same or different R ¹⁰ ;

R ⁹ is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocycloxy, heterocarbocycloxy, aryloxy, heteroaryloxy, heterocycloxy, cycloalkoxy, cycloalkenoxy, alkylamino, (alkyl) ₂ amino, carbocyclamino, heterocarbocyclamino, arylamino, heteroarylamino, heterocyclamino, cycloalkamino, cycloalkenamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R ⁹ is optionally substituted with one or more of the same or different R ¹⁰ ;

R ⁷ , R ⁸ and R ⁹ can form a ring with the α-carbon atom to which they are attached and with an amino group attached to the α-carbon atom;

R ⁸ and R ⁹ may form a ring with the α-carbon atom to which they are attached;

22. Pharmaceutical composition according to claim 21, characterized in that R ¹ represents hydrogen, , , .

23. The pharmaceutical composition according to claim 1, characterized in that R ^' represents methyl, fluorine, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, trideuteromethyl, thiomethyl, carboxylic acid, formyl, vinyl or ethynyl.

24. The pharmaceutical composition according to claim 1, characterized in that R ^” represents methyl, fluorine, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, trideuteromethyl, thiomethyl, carboxylic acid, formyl, vinyl or ethynyl.

25. The pharmaceutical composition according to claim 2, characterized in that R ^' represents methyl, fluorine, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, trideuteromethyl, thiomethyl, carboxylic acid, formyl, vinyl or ethynyl.

26. The pharmaceutical composition according to claim 2, characterized in that R ^” represents methyl, fluorine, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, trideuteromethyl, thiomethyl, carboxylic acid, formyl, vinyl or ethynyl.

27. The pharmaceutical composition according to claim 3, characterized in that R ^” represents methyl, fluorine, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, trideuteromethyl, thiomethyl, carboxylic acid, formyl, vinyl or ethynyl.

28. Pharmaceutical composition according to any one of paragraphs. 2-5 or 8-17, characterized in that R ¹ , R ² , R ³ and R ⁵ are each independently selected from H,

, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ;

with the proviso that not all R ¹ , R ² , R ³ and R ⁵ are H;

R ⁷ , R ⁸ and R ⁹ may form a ring with the α-carbon atom to which they are attached and with an amino group attached to the α-carbon atom;

29. Pharmaceutical composition according to claim 6 or 7, characterized in that R ¹ , R ² and R ³ are each independently selected from the following:

R ⁶ represents hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, optionally substituted phenyl, optionally substituted aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocycloxy, heterocarbocycloxy, aryloxy, heteroaryloxy, heterocycloxy, cycloalkoxy, cycloalkenoxy, alkylamino, (alkyl) ₂ amino, carbocyclamino, heterocarbocyclamino, arylamino, heteroarylamino, heterocyclamino, cycloalkamino, cycloalkenamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, cyano or lipid, with R ⁶ optional replaced by one or more same or different R ¹⁰ ;

30. Pharmaceutical composition according to claim 18, characterized in that R ¹ is selected from the following:

R ⁶ is hydrogen, C ₁ -C ₇ n-alkyl, C ₉ -C ₂₂ n-alkyl, optionally substituted C ₈ n-alkyl, branched alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl , cycloalkenyl, -O(C ₁ -C ₆ n-alkyl), -O(C ₈ -C ₂₁ n-alkyl), optionally substituted -O(C ₇ n-alkyl), -O(branched alkyl), carbocycloxy, heterocarbocycloxy, aryloxy, heteroaryloxy, heterocycloxy, cycloalkoxy, cycloalkenoxy, -NH(C ₁ -C ₆ n-alkyl), -NH(C ₈ -C ₂₁ n-alkyl), optionally substituted -NH(C7 n-alkyl), - NH(branched alkyl), (alkyl) ₂ amino, carbocyclamino, heterocarbocyclamino, arylamino, heteroarylamino, heterocyclamino, cycloalkamino, cycloalkenamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, cyano or lipid, and R ⁶ is optionally substituted with one or more identical or different R ¹⁰ ;

31. Pharmaceutical composition according to claim 19, characterized in that R ⁵ is selected from the following:

R ⁶ is hydrogen, C ₂ -C ₇ n-alkyl, optionally substituted C ₈ n-alkyl, C ₉ -C ₂₂ n-alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, C ₃ -C ₉ cycloalkyl, C ₁₁ -C ₂₂ cycloalkyl, optionally substituted C ₁₀ cycloalkyl, cycloalkenyl, -O(C ₁ -C ₆ n-alkyl), -O(optionally substituted C ₇ n-alkyl), -O(C ₈ -C ₂₁ n-alkyl), -O(branched alkyl), carbocycloxy, heterocarbocycloxy, aryloxy, heteroaryloxy, heterocycloxy, cycloalkoxy, cycloalkenoxy, -N(C ₂ -C ₂₁ n-alkyl) ₂ , -N(optionally substituted C ₁ alkyl) ₂ , -NH(optionally substituted C ₁ alkyl), -NH(C ₂ -C ₆ n-alkyl), -NH(optionally substituted C ₇ n-alkyl), -NH(C ₈ -C ₁₅ n-alkyl), -NH(optionally substituted C ₁₆ n-alkyl), -NH(C ₁₇ n-alkyl), -NH(optionally substituted C ₁₈ n-alkyl), -NH(C ₁₉ -C ₂₁ n-alkyl), -NH( branched alkyl), -N(branched alkyl) ₂ , carbocyclamino, heterocarbocyclamino, optionally substituted arylamino, heteroarylamino, heterocyclamino, cycloalkamino, cycloalkenylthio, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, al lenil, cyano or lipid, wherein R ⁶ is optionally substituted with one or more identical or different R ¹⁰ ;

32. A pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound selected from the following:

.

33. A pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound selected from the following:

.

34. A pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound selected from the following:

.

35. A pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound selected from the following:

.

36. A pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound selected from the following:

.

37. A pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound selected from the following:

.

38. A pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound selected from the following:

.

39. A pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound selected from the following:

.

40. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of the following structure:

or pharmaceutically acceptable or physiological salts thereof.

41. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of the following structure:

or pharmaceutically acceptable or physiological salts thereof.

42. Pharmaceutical composition containing a pharmaceutically acceptable excipient and a compound of the following structure:

or pharmaceutically acceptable or physiological salts thereof.

43. Pharmaceutical composition according to any one of paragraphs. 1-42, characterized in that it additionally contains a propellant gas.

44. The pharmaceutical composition according to claim 43, characterized in that the propellant gas is compressed air, ethanol, nitrogen, carbon dioxide, nitrogen oxide (I), hydrofluoroalkanes (HFA), 1,1,1,2-tetrafluoroethane, 1 ,1,1,2,3,3,3-heptafluoropropane or combinations thereof.

45. A pressurized container containing a pharmaceutical composition according to any one of paragraphs. 1-42.

46. The container of claim 45, characterized in that it is an aerosol hand pump, an inhaler, a metered dose inhaler, a dry powder inhaler, a nebulizer, a vibrating mesh nebulizer, a jet nebulizer, or an ultrasonic nebulizer.

47. A method of treating or preventing a viral infection, comprising administering an effective amount of a compound according to any one of claims. 1-42 to the subject in need.

48. The method according to claim 47, characterized in that the viral infection is an alphavirus.

49. The method of claim 48, wherein the virus is selected from Eastern Equine Encephalitis Virus, Western Equine Encephalitis Virus, Venezuelan Equine Encephalitis Virus, Chikungunya Virus and Ross River Virus.

50. The method according to claim 47, characterized in that the viral infection is a coronavirus.

51. The method according to claim 50, characterized in that the viral infection is a human coronavirus, SARS coronavirus or MERS coronavirus.

52. The method according to claim 47, characterized in that the viral infection is a Filoviridae virus.

53. The method according to claim 52, characterized in that the viral infection is the Ebola virus.

54. The method according to claim 47, characterized in that the viral infection is an Orthomyxoviridae virus.

55. The method according to claim 54, characterized in that the viral infection is an influenza A virus and an influenza B virus.

56. The method according to claim 47, characterized in that the viral infection is a Paramyxoviridae virus.

57. The method according to claim 56, characterized in that the viral infection is RSV.

58. A method of treating or preventing human coronavirus, SARS coronavirus, MERS coronavirus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Chikungunya virus and Ross River infection, Orthomyxoviridae virus or Paramyxoviridae virus, or RSV virus, or virus influenza A and influenza B virus, or Filoviridae virus, or Ebola virus infection in a patient, comprising administering to the patient in need thereof an effective amount of a compound of the structure

or pharmaceutically acceptable or physiological salts thereof.

59. A method of treating or preventing human coronavirus, SARS coronavirus, MERS coronavirus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Chikungunya virus and Ross River infection, Orthomyxoviridae virus or Paramyxoviridae virus, or RSV virus, or virus influenza A and influenza B virus, or Filoviridae virus, or Ebola virus infection in a patient, comprising administering to the patient in need thereof an effective amount of a compound of the structure

or pharmaceutically acceptable or physiological salts thereof.

60. A method of treating or preventing human coronavirus, SARS coronavirus, MERS coronavirus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Chikungunya virus and Ross River infection, Orthomyxoviridae virus or Paramyxoviridae virus, or RSV virus, or virus influenza A and influenza B virus, or Filoviridae virus, or Ebola virus infection in a patient, comprising administering to the patient in need thereof an effective amount of a compound of the structure

or pharmaceutically acceptable or physiological salts thereof.