US 12,630,524 B2 · Pleuromutilin in derivatives for treating viral infections

Abstract

A compound selected from 14-O-[((Alkyl-, cycloalkyl-, heterocycloalkyl-, heteroaryl-, or aryl)-sulfanyl)-acetyl]-12-epi-mutilins, or 14-O-[((Alkyl-, cycloalkyl-, heterocycloalkyl-, heteroaryl-, or aryl)-oxy)-acetyl]-12-epi-mutilins, wherein 12-epi-mutilin is characterized in that the mutilin ring at position 12 is substituted by two substituents, the first substituent at position 12 of the mutilin ring is a methyl group which methyl group has the inverse stereochemistry compared with the stereochemistry of the methyl group at position 12 of the naturally occurring pleuromutilin ring, the second substituent at position 12 of the mutilin ring is a hydrocarbon group comprising at least one nitrogen atom and all other substituents of the mutilin ring having the same stereochemistry compared with the stereochemistry of the substituents at the corresponding positions in the naturally occurring pleuromutilin ring; optionally in the form of a pharmaceutically acceptable salt and/or solvate, prodrug or metabolite, wherein the naturally occurring pleuromutilin is of formula. for the specific use in the treatment or prevention of a disease mediated by a virus. The invention further relates to 12-epi-12-desvinyl-14-O-[(Piperidin-4-ylsulfanyl]-acetyl]-12-[2-(3-methyl-pyrazin-2-yl)-ethenyl]-mutilin and its therapeutic uses.

Claims22

Dependent claims

A compound of formula (II)

or a pharmaceutically acceptable salt or solvate thereof.

A method for treating or preventing a viral infection, comprising administering to a subject in need thereof a compound of formula (I)

wherein R1 is (C1-16)alkyl or (C2-16)alkenyl substituted by heterocyclyl including aliphatic and aromatic heterocyclyl and comprising 1 to 4 heteroatoms selected from N, O, and S, provided that at least one heteroatom is a nitrogen atom, or R1 is
wherein Y—N(R3R4) is
(C1-16)alkyl-N(R3R4),
(C1-16)alkyl-(C6-14)aryl-N(R3R4),
(C1-16)alkyl-(C6-14)aryl-(C1-16)alkyl-N(R3R4),
(C1-16)alkyl-(C1-13)heterocyclyl-N(R3R4),
(C1-16)alkyl-(C1-13)heterocyclyl-(C1-16)alkyl-N(R3R4),
carbonyl-N(R3R4),
(C1-4)alkyl-carbonyl-N(R3R4),
(C2-16)alkenyl-N(R3R4),
(C2-16)alkenyl-(C6-14)aryl-N(R3R4),
(C2-16)alkenyl-(C6-14)aryl-(C1-16)alkyl-N(R3R4),
(C2-16)alkenyl-(C1-13)heterocyclyl-N(R3R4), or
(C2-16)alkenyl-(C1-13)heterocyclyl-(C1-16)alkyl-N(R3R4),
wherein heterocyclyl includes aliphatic and aromatic heterocyclyl and comprises at least one heteroatom selected from N, O, and S, and
wherein alkyl, aryl, heterocyclyl, or alkenyl is optionally substituted by one or more substituents optionally having one or more heteroatoms selected from O, N, S, and halogen;
wherein each of R3 and R4 is independently
hydrogen,
(C1-16)alkyl,
(C2-16)alkenyl,
hydroxy-(C1-16)alkyl,
amino-(C1-16)alkyl,
mono- or di-(C1-6)alkylamino(C1-16)alkyl,
guanidino (C1-16)alkyl, ureido (C1-16)alkyl, or thioureido (C1-16)alkyl,
amino (C1-6)alkyl-(C6-14)aryl-(C1-6)alkyl,
amino(C1-6)alkyl-(C6-14)aryl,
guanidino (C1-6)alkyl-(C6-14)aryl-(C1-6)alkyl,
amino(C1-6)alkyloxy-(C1-6)alkyl,
amino(C3-8) cycloalkyl,
amino(C1-6)alkyl-(C3-8) cycloalkyl,
amino(C3-8) cycloalkyl-(C1-6)alkyl,
amino(C1-6)alkyl-(C3-8) cycloalkyl-(C1-6)alkyl,
(C1-13)heterocyclyl-(C1-16)alkyl,
(C6-14)aryl-(C1-16)alkyl,
(C1-13)heterocyclyl,
amino(C6-14)aryl-(C1-16)alkyl,
amino(C1-6)alkyloxy-(C6-14)aryl-(C1-6)alkyl,
amino(C1-6)alkyl-(C6-12)aryl-carbonyl,
amino(C1-6)alkyl-amido-(C6-12)aryl(C1-6)alkyl,
(C1-4)alkylcarbonyl, or
carbamimidoyl, carbamoyl, or thiocarbamoyl,
wherein heterocyclyl includes aliphatic and aromatic heterocyclyl and comprises at least one heteroatom selected from N, O, and S, and
wherein alkyl, cycloalkyl, heterocyclyl, alkenyl, or aryl is optionally substituted by
amino(C1-4)alkyl, amido, mono- or di-(C1-4)alkyl-amido, (C1-6)alkyloxy-carbonyl, halogen, oxo, or hydroxy,
wherein X is sulfur or oxygen, and
wherein R2 is a hydrocarbon group comprising 1 to 22 carbon atoms, optionally comprising heteroatoms selected from N, O, S, and halogen, or a pharmaceutically acceptable salt or solvate, thereof.

43 more elements

Dependencies are inferred from the claim text.

Pleuromutilin in derivatives for treating viral infections

Life of this patent

Pleuromutilin in derivatives for treating viral infections

Life of this patent

Abstract

Claims22