Granted Patent B2

US 12,630,524 · App. 17/919,204 · Granted May 19, 2026

Inventors: Susanne Paukner (Vienna, AT); Rosemarie Riedl (Vienna, AT); Wolfgang Wicha (Bruck an der Leitha, AT)

Assignee: ARIVA MED GMBH

C07D401/12A61P31/04A61P31/14C07D241/04

Abstract

Claims (287)

1 . A compound of formula (II)

or a pharmaceutically acceptable salt or solvate thereof.

2 . A pharmaceutical composition comprising a compound of claim 1 or the pharmaceutically acceptable salt or solvate thereof, with at least one pharmaceutical excipient, optionally further comprising another pharmaceutically active agent.

3 . A method of treating or preventing a viral infection comprising administering to a subject in need thereof a compound of claim 1 or the pharmaceutically acceptable salt or solvate thereof.

4 . The method according to claim 3 , wherein the viral infection relates to a respiratory disease.

5 . The method according to claim 3 , wherein the viral infection relates to an acute respiratory syndrome optionally including Influenza, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) or COVID-19.

6 . The method according to claim 3 , wherein the viral infection is associated with a virus being a positive- or negative-sense single-stranded RNA virus, optionally the virus is

Coronaviridae, optionally including human coronavirus,

Paramyxoviridae, optionally including Paramyxovirinae, optionally including Measles virus, or Pneumovirinae, optionally including Respiratory Syncytial Virus,

Orthomyxoviridae, optionally including Influenza virus,

Flaviviridae, optionally including Dengue virus or Zika virus, or

Picornaviridae, optionally including Rhinovirus.

7 . The method according to claim 3 , wherein the viral infection relates to an airborne disease.

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

wherein R 1 is (C 1-16 )alkyl or (C 2-16 )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 R 1 is

wherein Y—N(R 3 R 4 ) is

(C 1-16 )alkyl-N(R 3 R 4 ),

(C 1-16 )alkyl-(C 6-14 )aryl-N(R 3 R 4 ),

(C 1-16 )alkyl-(C 6-14 )aryl-(C 1-16 )alkyl-N(R 3 R 4 ),

(C 1-16 )alkyl-(C 1-13 )heterocyclyl-N(R 3 R 4 ),

(C 1-16 )alkyl-(C 1-13 )heterocyclyl-(C 1-16 )alkyl-N(R 3 R 4 ),

carbonyl-N(R 3 R 4 ),

(C 1-4 )alkyl-carbonyl-N(R 3 R 4 ),

(C 2-16 )alkenyl-N(R 3 R 4 ),

(C 2-16 )alkenyl-(C 6-14 )aryl-N(R 3 R 4 ),

(C 2-16 )alkenyl-(C 6-14 )aryl-(C 1-16 )alkyl-N(R 3 R 4 ),

(C 2-16 )alkenyl-(C 1-13 )heterocyclyl-N(R 3 R 4 ), or

(C 2-16 )alkenyl-(C 1-13 )heterocyclyl-(C 1-16 )alkyl-N(R 3 R 4 ),

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 R 3 and R 4 is independently

hydrogen,

(C 1-16 )alkyl,

(C 2-16 )alkenyl,

hydroxy-(C 1-16 )alkyl,

amino-(C 1-16 )alkyl,

mono- or di-(C 1-6 )alkylamino(C 1-16 )alkyl,

guanidino (C 1-16 )alkyl, ureido (C 1-16 )alkyl, or thioureido (C 1 -16)alkyl,

amino (C 1-6 )alkyl-(C 6-14 )aryl-(C 1-6 )alkyl,

amino(C 1-6 )alkyl-(C 6-14 )aryl,

guanidino (C 1-6 )alkyl-(C 6-14 )aryl-(C 1-6 )alkyl,

amino(C 1-6 )alkyloxy-(C 1-6 )alkyl,

amino(C 3-8 ) cycloalkyl,

amino(C 1-6 )alkyl-(C 3-8 ) cycloalkyl,

amino(C 3-8 ) cycloalkyl-(C 1-6 )alkyl,

amino(C 1-6 )alkyl-(C 3-8 ) cycloalkyl-(C 1-6 )alkyl,

(C 1-13 )heterocyclyl-(C 1-16 )alkyl,

(C 6-14 )aryl-(C 1-16 )alkyl,

(C 1-13 )heterocyclyl,

amino(C 6-14 )aryl-(C 1-16 )alkyl,

amino(C 1-6 )alkyloxy-(C 6-14 )aryl-(C 1-6 )alkyl,

amino(C 1-6 )alkyl-(C 6-12 )aryl-carbonyl,

amino(C 1-6 )alkyl-amido-(C 6-12 )aryl(C 1-6 )alkyl,

(C 1-4 )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(C 1-4 )alkyl, amido, mono- or di-(C 1-4 )alkyl-amido, (C 1-6 )alkyloxy-carbonyl, halogen, oxo, or hydroxy,

wherein X is sulfur or oxygen, and

wherein R 2 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.

9 . The method according to claim 8 , wherein, in the compound or the pharmaceutically acceptable salt or solvate, thereof, R 2 is

(C 1-16 )alkyl,

(C 3-12 ) cycloalkyl,

(C 1-13 )heterocyclyl, or

(C 6-14 )aryl,

wherein heterocyclyl includes aliphatic and aromatic heterocyclyl and comprises at least one heteroatom selected from N, O, and S, and

wherein alkyl, cycloalkyl, aryl, heterocyclyl is optionally substituted by one or more substituents having one or more heteroatoms selected from O, N, S, and halogen.

10 . The method according to claim 9 , wherein, in the compound or the pharmaceutically acceptable salt or solvate thereof, R 2 is

(C 1-16 )alkyl, optionally substituted by

hydroxy or amino,

(C 3-12 ) cycloalkyl optionally substituted by amino or amino(C 1-4 )alkyl, the amino or amino(C 1-4 )alkyl optionally further substituted by amino(C 1-6 )alkylcarbonyl or (C 1-4 )alkyl,

(C 2-11 )heterocyclyl having at least one nitrogen heteroatom and being optionally further substituted by amino(C 1-6 )alkylcarbonyl;

R 2 is cycloalkyl, optionally substituted by

amino(C 1-4 )alkyl, wherein amino is optionally further substituted by amino(C 1-6 )alkylcarbonyl,

hydroxy,

amino optionally substituted by amino(C 1-6 )alkylcarbonyl or (C 1-4 )alkyl,

amino and hydroxy, wherein amino is optionally further substituted by amino(C 1-6 )alkylcarbonyl or (C 1-4 )alkyl,

(C 1-4 )alkylamino optionally further substituted by one or more halogen atoms;

R 2 is aliphatic (C 2-11 )heterocyclyl comprising 1 to 4 heteroatoms selected from N, O, and S, wherein a nitrogen heteroatom is optionally substituted by

(C 1-4 )alkyl, or

amino(C 1-6 )alkylcarbonyl;

R 2 is aryl optionally substituted by

hydroxy, halogen, amino, hydroxy (C 1-4 )alkyl, bis-(hydroxy (C 1-4 )alkyl), amino(C 1-4 )alkyl, bis-(amino(C 1-4 )alkyl), wherein amino in amino(C 1-4 )alkyl is optionally further substituted,

(C 1-6 )alkyl optionally substituted by aminocarbonyl, wherein the nitrogen of the aminocarbonyl group is optionally further substituted by amino(C 1-12 )alkyl, diamino-(C 1-12 )alkyl, bis-(amino(C 1-12 )alkyl), hydroxy (C 1-6 )alkyl, bis-(hydroxy (C 1-6 )alkyl),

acylated amino(C 1-4 )alkyl,

aminocarbonyl, wherein nitrogen is optionally further substituted by amino(C 1-12 )alkyl, bis-(amino(C 1-12 )alkyl), hydroxy (C 1-6 )alkyl,

bis-(hydroxy (C 1-6 )alkyl), diamino(C 1-6 )alkyl, or

(C 1-12 )alkyl, optionally further substituted by

amino, optionally further substituted by formyl,

(C 1-4 )alkylcarbonyl, a 4- to 8-membered saturated or unsaturated heterocyclyl comprising 1 to 3 heteroatoms selected from N, O, and S, or (C 6-14 )aryl optionally further substituted by amino(C 1-4 )alkyl

or wherein nitrogen is part of (C 3-8 )heterocyclyl, including aliphatic and aromatic heterocyclyl, comprising one or more heteroatoms selected from N, O, S and being optionally further substituted by amino(C 1-4 )alkyl; or

R 2 is aromatic (C 1-13 )heterocyclyl comprising 1 to 4 heteroatoms and being optionally substituted by (C 1-6 )alkyl, amino, or hydroxy, wherein alkyl is optionally further substituted by halogen or amino, or being optionally substituted by aminocarbonyl,

wherein amino is optionally further substituted by amino(C 1-12 )alkyl, bis-(amino(C 1 -12)alkyl), hydroxy (C 1-6 )alkyl, bis-(hydroxy (C 1-6 )alkyl), or diamino(C 1-6 )alkyl.

11 . The method according to claim 8 , wherein, in the compound or the pharmaceutically acceptable salt or solvate thereof, R 2 is amido-phenyl, amido (C 1-4 )alkyl-phenyl, wherein nitrogen of amido is optionally substituted by amino(C 1-8 )alkyl, wherein alkyl is optionally further substituted.

12 . The method according to claim 8 , wherein, in the compound or the pharmaceutically acceptable salt or solvate thereof, R 2 is

amino(C 3-12 ) cycloalkyl,

amino(C 1-4 )alkyl(C 3-12 ) cycloalkyl,

amino(C 3-12 ) cycloalkyl(C 1-4 )alkyl, or

amino(C 1-4 )alkyl(C 3-12 ) cycloalkyl(C 1-4 )alkyl,

wherein amino is optionally substituted by amino(C 1-6 )alkylcarbonyl or (C 1-4 )alkyl.

13 . The method according to claim 8 , wherein, in the compound or the pharmaceutically acceptable salt or solvate thereof, R 2 is (C 2-11 )heterocyclyl comprising 1 to 4 heteroatoms selected from N, O, S, wherein, if R 2 has at least one nitrogen heteroatom, the at least one nitrogen heteroatom is optionally substituted by

(C 1-4 )alkyl, or

amino(C 1-6 )alkylcarbonyl.

14 . The method according to claim 8 , wherein, in the compound or the pharmaceutically acceptable salt or solvate thereof,

X is S, and

R 2 is

aminoethyl-amidomethyl-phenyl, aminopropyl-amidomethyl-phenyl, hydroxyphenyl-(amino)ethyl-amidomethyl-phenyl, aminomethyl-phenyl-(amino)ethyl-amidomethyl-phenyl, aminopropyl-amidophenyl, aminomethyl-phenylmethyl-amido-phenyl, aminomethyl-phenyl, aminoacetyl-aminomethyl-phenyl, bis(aminomethyl)phenyl, bisaminopropyl-amidomethyl-phenyl, (2-amino)-aminopropyl-amidomethyl-phenyl, aminoethyl-aminomethyl-phenyl, aminopropyl-aminomethyl-phenyl, allyl-aminomethyl-phenyl, aminomethyl-phenylmethyl-aminomethyl-phenyl, hydroxymethyl-phenyl, bis(hydroxymethyl)-phenyl, (tetrafluoro-hydroxymethyl)-phenyl, amino-hydroxy-cyclohexyl, hydroxyethyl, aminoethyl, piperazinocarbonyl-phenyl, aminomethyl-piperidine-carbonyl-phenyl, piperidine-ylmethyl-amido-phenyl, pyridine-ylmethyl-amido-phenyl, acetyl-aminopropyl-amido-phenyl, formyl-aminopropyl-amido-phenyl, amido-phenyl, aminohexyl-amidophenyl, aminoethyl-amidophenyl, (5-Amino)-4H-[1,2,4]triazol-3-yl, pyridinyl, hydroxyphenyl, fluorophenyl, purinyl, aminophenyl, acetyl-aminomethyl-phenyl, cyclopropyl-aminomethyl-phenyl, aminopropyl-amidopyridinyl, hydroxypropyl-amidophenyl, amino-purinyl, difluoroethylamino-cyclohexyl, amino-hydroxy-cyclohexyl, azepanyl, aminomethylcyclohexylmethyl, N-methyl-piperidinyl, piperidinyl, aminomethylcyclohexyl, aminopropylphenyl, phenyl, N-aminomethylcarbonyl-piperidinyl, N-aminoethylcarbonyl-piperidinyl, N-aminomethylcarbonyl-piperidinylmethyl, aminomethylamidomethylcyclohexyl, aminomethyl-pyridinyl, or aminomethylamidocyclohexyl.

15 . The method according to claim 8 , wherein the compound is of formula (III)

wherein

n is 1 to 12,

R 3 is H, aminoethyl, aminopropyl, aminobutyl, aminopentyl, aminohexyl, aminooctyl, aminodecyl, dimethylaminopropyl, dimethylamidopentyl, guanidinobutyl, guanidinohexyl, carbamimidoyl, aminomethylcyclohexylmethyl, aminopropoxypropyl, aminocyclohexyl, hydroxyhexyl, dihydroxypropyl, aminomethylphenylmethyl, guanidinomethylphenylmethyl, phenylmethyl, morpholinopropyl, piperidinyl, hexyl, pyridinylethyl, allyl, amido-benzyl, aminopropyl-amidobenzyl, (2-amino)-amidoethyl-benzyl, (2-amino)-dimethylamidoethyl-benzyl, 2-amino-1-aminomethyl-ethyl, 5-amino-5-ethoxycarbonyl-pentyl, aminomethylphenylpropyl, aminomethylphenyl, aminophenymethyl, aminoethoxyphenylmethyl, aminomethyl-fluorophenyl-methyl, or aminomethyl-difluorophenyl-methyl, and

R 4 is H, (C 1-4 )alkylcarbonyl, or aminomethylphenylcarbonyl

or a pharmaceutically acceptable salt or solvate, prodrug or metabolite thereof.

16 . The method according to claim 8 , wherein, in the compound or the pharmaceutically acceptable salt or solvate thereof,

R 1 is aminomethylphenylpropyl, aminoethylaminomethylphenylethenyl, aminoethylaminomethylphenylethyl, aminomethylphenylethyl, aminomethylphenylethyl, pyridinylethenyl, or aminoethylamino-fluorophenyl-ethenyl.

17 . The method according to claim 8 , wherein the compound or the pharmaceutically acceptable salt or solvate thereof is selected from

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(2-Amino-ethylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-([Bis-(3-amino-propyl)-carbamoyl]-methyl}-phenylsulfanyl)-acetyl}-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(2,3-Diamino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(2-Amino-ethylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(2-amino-ethylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(2-amino-ethylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(4-amino-butylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(5-amino-pentylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(4-aminomethyl-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(6-guanidino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(4-guanidino-butylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(allylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-aminomethyl mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(4-guanidinomethyl-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(6-hydroxy-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(2,3-dihydroxypropylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(4-piperidylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(3-morpholin-4-yl-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(3-dimethylamino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[(S)-5-amino-5-ethoxycarbonyl-pentylamino-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[4-(4-Aminomethyl-benzylcarbamoyl)-phenylsulfanyl]-acetyl}-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[4-(4-Aminomethylbenzylcarbamoyl)-phenylsulfanyl]-acetyl}-12-[(6-guanidino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[(4-Piperazinylcarbamoyl)-phenylsulfanyl]-acetyl}-12-[(6-guanidino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[4-(4-Aminomethyl-piperidine-1-carbonyl)-phenylsulfanyl]-acetyl}-12-[(6-guanidino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{(4-[(Piperidin-4-ylmethyl)-carbamoyl]-phenylsulfanyl)-acetyl}-12-[(6-guanidino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{(4-[(Pyridin-4-ylmethyl)-carbamoyl]-phenylsulfanyl)-acetyl}-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[3-(3-Aminopropylcarbamoyl)-phenylsulfanyl]-acetyl}-12-[(6-guanidino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[4-(3-Acetylamino-propylcarbamoyl)-phenylsulfanyl]-acetyl}-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[4-(3-Formylamino-propylcarbamoyl)-phenylsulfanyl]-acetyl}-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[4-(3-Amino-propylcarbamoyl)-phenylsulfanyl]-acetyl}-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{(4-[(3-Aminopropylcarbamoyl)-phenylsulfanyl)-acetyl}-12-[(4-aminomethyl-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{(4-[(3-Aminopropylcarbamoyl)-phenylsulfanyl)-acetyl}-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[4-(3-Aminopropylcarbamoyl)-phenylsulfanyl]-acetyl}-12-[(6-guanidino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[4-(3-Aminopropylcarbamoyl)-phenylsulfanyl]-acetyl}-12-[(8-amino-octylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[4-(3-Aminopropylcarbamoyl)-phenylsulfanyl]-acetyl}-12-[(10-amino-decylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{(4-Carbamoyl-phenylsulfanyl)-acetyl}-12-[(6-guanidino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[4-(3-Amino-propylcarbamoyl)-phenylsulfanyl]-acetyl}-12-{[3-(3-amino-propoxy)-propylamino)]-methyl}mutilin,

12-epi-12-desvinyl-14-O-{[4-(3-Amino-propylcarbamoyl)-phenylsulfanyl]-acetyl}-12 [(2-pyridin-4-yl-ethylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[4-(6-Amino-hexylcarbamoyl)-phenylsulfanyl]-acetyl}-12-[(6-guanidino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[4-(2-Amino-ethylcarbamoyl)-phenylsulfanyl]-acetyl}-12-[(6-guanidino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[4-(3-Aminopropylcarbamoyl)-phenylsulfanyl]-acetyl}-12-{[3-(4-aminomethyl-phenyl)-propylamino]-methyl}mutilin,

12-epi-12-desvinyl-14-O-{[(4-Aminomethyl-cyclohexyl)-methylsulfanyl]-acetyl}-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-14-O-[(1-Methyl-piperidin-4-ylsulfanyl)-acetyl}-12-[(6-guanidino-hexylamino)-methyl]mutilin,

12-epi-14-O-[(Piperidin-4-ylsulfanyl)-acetyl]-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[(4-Aminomethyl-cyclohexyl)-sulfanyl]-acetyl}-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[4-(3-Amino-propyl)-phenylsulfanyl]-acetyl}-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{(4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl)-acetyl}-12-{[(3-amino-propyl)-acetylamino]-methyl}mutilin,

12-epi-12-desvinyl-14-O-{(4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl)-acetyl}-12-(3-amino-propylcarbamoyl) mutilin,

12-epi-12-desvinyl-14-O-{[4-(3-Amino-propylcarbamoyl)-phenylsulfanyl]-acetyl}-12-(4-aminomethyl-benzylcarbamoyl) mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylcarbamoyl)-methyl]-phenylsulfanyl}-acetyl}-12-[2-(3-amino-propylamino)-ethyl]mutilin,

12-epi-12-desvinyl-14-O-[(3-Hydroxymethyl-phenylsulfanyl)-acetyl]-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(3-Hydroxymethyl-phenylsulfanyl)-acetyl]-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(3-Hydroxymethyl-phenylsulfanyl)-acetyl]-12-[(4-aminomethyl-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(3-Hydroxymethyl-phenylsulfanyl)-acetyl]-12-[(6-guanidino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(4-Hydroxymethyl-phenylsulfanyl)-acetyl]-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(4-Hydroxymethyl-phenylsulfanyl)-acetyl]-12-[(4-aminomethyl-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(4-Hydroxymethyl-phenylsulfanyl)-acetyl]-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(3,5-Bis-hydroxymethyl-phenylsulfanyl)-acetyl]-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[(2,3,5,6-Tetrafluoro-4-hydroxymethyl)-phenylsulfanyl]-acetyl}-12-[(4-aminomethyl-benzylamino)-methyl]-mutilin,

12-epi-12-desvinyl-14-O-{[(1R,2R,4R)-4-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[(1R,2R,4R)-4-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-12-[(4-aminomethyl-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(2-Hydroxy-ethylsulfanyl)-acetyl]-12-[(4-aminomethyl-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(2-Amino-ethylsulfanyl)-acetyl]-12-[(4-aminomethyl-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[(5-Amino-4H-1,2,4-triazol-3-yl)-sulfanyl]-acetyl}-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(2-Amino-ethylsulfanyl)-acetyl]-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(Pyridin-4-ylsulfanyl)-acetyl]-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(Pyridin-4-ylsulfanyl)-acetyl]-12-[(6-guanidino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(3-Hydroxy-phenylsulfanyl)-acetyl]-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(4-Fluoro-phenylsulfanyl)-acetyl]-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[(7H-Purin-6-yl)-sulfanyl]-acetyl}-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(3-Amino-phenylsulfanyl)-acetyl]-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-(Phenylsulfanyl-acetyl)-12-[(4-aminomethyl-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(4-Fluoro-phenylsulfanyl)-acetyl]-12-[(4-aminomethyl-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(Pyridin-2-ylsulfanyl)-acetyl]-12-[(4-aminomethyl-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(Pyridin-4-ylsulfanyl)-acetyl]-12-[(4-aminomethyl-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[1-(2-Amino-acetyl)-piperidin-4-yl-sulfanyl)]-acetyl}-12-[(4-aminomethyl-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[1-(3-Amino-propionyl)-piperidin-4-yl-sulfanyl)]-acetyl}-12-[(4-aminomethyl-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[1-(3-Amino-propionyl)-piperidin-4-yl-sulfanyl]-acetyl}-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[1-(2-Amino-acetyl)-piperidin-4-yl-methylsulfanyl]-acetyl}-12-[(4-aminomethyl-phenylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[1-(2-Amino-acetyl)-piperidin-4-yl-methylsulfanyl]-acetyl}-12-[(4-amino-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[1-(2-Amino-acetyl)-piperidin-4-yl-sulfanyl]-acetyl}-12 {2-[4-(2-amino-ethoxy)-benzylamino]-methyl}mutilin,

12-epi-12-desvinyl-14-O-{{4-[(2-Amino-acetylamino)-methyl]-cyclohexylsulfanyl}-acetyl}-12-[{4-[(2-amino-ethoxy)-benzylamino]-methyl}mutilin,

12-epi-12-desvinyl-14-O-[(4-Aminomethyl-phenylsulfanyl)-acetyl]-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(3-Aminomethyl-phenylsulfanyl)-acetyl]-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(3-Aminomethyl-phenylsulfanyl)-acetyl]-12-[(6-guanidino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(4-Aminomethyl-phenylsulfanyl)-acetyl]-12-[(4-aminomethyl-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(4-Aminomethyl-phenylsulfanyl)-acetyl]-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(3-Aminomethyl-phenylsulfanyl)-acetyl]-12-[((4-aminomethyl-cyclohexyl)-methylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(4-Aminomethyl-phenylsulfanyl)-acetyl]-12-{[(4-aminocyclohexyl)-amino]-methyl}mutilin,

12-epi-12-desvinyl-14-O-[(4-Aminomethyl-phenylsulfanyl)-acetyl]-12-[(hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(4-Aminomethyl-phenylsulfanyl)-acetyl]-12-[(4-carbamoylphenyl)-methylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(4-Aminomethyl-phenylsulfanyl)-acetyl]-12-{[4-(3-amino-propylcarbamoyl)-benzylamino]-methyl}mutilin,

12-epi-12-desvinyl-14-O-[(4-Aminomethyl-phenylsulfanyl)-acetyl]-12-[(5-dimethylcarbamoyl-pentylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(4-Aminomethyl-phenylsulfanyl)-acetyl]-12-{[4-(2-amino-2-carbamoyl-ethyl)-benzylamino]-methyl}mutilin,

12-epi-12-desvinyl-14-O-[(4-Aminomethyl-phenylsulfanyl)-acetyl]-12-{[4-(2-amino-2-dimethylcarbamoyl-ethyl)-benzylamino]-methyl}mutilin,

12-epi-12-desvinyl-14-O-{[5-Aminomethyl-pyridin-2-yl-sulfanyl)]-acetyl}-12-[(4-aminomethyl-benzylamino)-methyl]mutilin,

12-epi-12-Desvinyl-14-O-{[5-aminomethyl-pyridin-2-yl-sulfanyl)]-acetyl}-12-[(4-aminomethyl-3-fluoro-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[(4-Aminomethyl-cyclohexyl)-methylsulfanyl)-acetyl]{[(4-Aminomethyl-cyclohexyl)-methylsulfanyl]-acetyl}-12-[(4-aminomethyl-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{1-(2-Amino-acetyl)-piperidin-4-yl-sulfanyl]-acetyl}-12-[(4-aminomethyl-3-fluoro-benzylamino)-methyl]mutilin,

12-epi-12-Desvinyl-14-O-{{4-[(2-Amino-acetylamino)-methyl]-cyclohexylsulfanyl}-acetyl}-12-[(4-aminomethyl-3-fluoro-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[5-Aminomethyl-pyridin-2-yl-sulfanyl]-acetyl}-12-[(4-aminomethyl-2,5-difluoro-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(4-Aminomethyl-phenylsulfanyl)-acetyl]-12-[(2-amino-1-aminomethyl-ethylamino)-methyl]mutilin,

12-epi-12-Desvinyl-14-O-[(5-aminomethyl-pyridin-2-yl-sulfanyl)-acetyl]-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{(4-[(2-Amino-acetylamino)-methyl]-phenylsulfanyl)-acetyl}-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{(4-[(2-Amino-3-(4-hydroxy-phenyl)-propionylamino)-methyl]-phenylsulfanyl)-acetyl}-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{(4-[(3-Amino-propionylamino)-methyl]-phenylsulfanyl)-acetyl}-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{(4-[(2-Amino-acetylamino)-methyl]-phenylsulfanyl)-acetyl}-12-[4-aminomethyl-benzylamino-methyl]mutilin,

12-epi-12-desvinyl-14-O-{(4-[(2-Amino-acetylamino)-methyl]-phenylsulfanyl)-acetyl}-12-(6-amino-hexylamino-methyl) mutilin,

12-epi-12-desvinyl-14-O-{[(3-Acetylamino-methyl)-phenylsulfanyl]-acetyl}-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{(4-{[2-Amino-3-(4-aminomethyl-phenyl)-propionylamino]-methyl}-phenylsulfanyl)-acetyl}-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylamino)-methyl]-phenylsulfanyl}-acetyl}-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{3-[(3-Amino-propylamino)-methyl]-phenylsulfanyl}-acetyl}-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(4-Aminomethyl-benzylamino)-methyl]-phenylsulfanyl}-acetyl}-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(3-Allylaminomethyl-phenylsulfanyl)-acetyl]-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(3-Amino-propylamino)-methyl]-phenylsulfanyl}-acetyl}-12-{[3-(3-amino-propoxy)-propylamino]-methyl}mutilin,

12-epi-12-desvinyl-14-O-[(4-Cyclopropylaminomethyl-phenylsulfanyl)-acetyl]-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(4-Cyclopropylaminomethyl-phenylsulfanyl)-acetyl]-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(4-Aminomethyl-benzylamino)-methyl]-phenylsulfanyl}-acetyl}-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(4-Aminomethyl-benzylamino)-methyl]-phenylsulfanyl}-acetyl}-12-[(4-aminomethyl-benzylamino)-methyl]-mutilin,

12-epi-12-desvinyl-14-O-[5-(3-Amino-propylcarbamoyl)-pyridin-2-ylsulfanyl]-acetyl-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(2,5-Bis-aminomethyl-phenylsulfanyl)-acetyl]-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(3,5-Bis-aminomethyl-phenylsulfanyl)-acetyl]-12-[(3-amino-propylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[(3-Amino-propylcarbamoyl)-phenylsulfanyl]-acetyl}-12-[(2-guanidino-ethyl]mutilin,

12-epi-12-desvinyl-14-O-{[4-(3-Hydroxy-propylcarbamoyl)-phenylsulfanyl]-acetyl}-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(2-Hydroxy-ethylsulfanyl)-acetyl]-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[3-(2,2-Difluoro-ethylamino)-cyclohexylsulfanyl]-acetyl}-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(2-Amino-7H-purin-6-ylsulfanyl)-acetyl]-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(Azepan-4-ylsulfanyl)-acetyl]-12-[(6-amino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(Azepan-4-ylsulfanyl)-acetyl]-12-[(6-guanidino-hexylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(Azepan-4-ylsulfanyl)-acetyl]-12-[(4-aminomethyl-benzylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-[(Azepan-4-ylsulfanyl)-acetyl]-12-[(6-amino-octylamino)-methyl]mutilin,

12-epi-12-desvinyl-14-O-{[1-(2-Amino-acetyl)-piperidin-4-yl-sulfanyl)]-acetyl}-12-[(6-amino-hexylamino)-ethyl]mutilin,

12-epi-12-desvinyl-14-O-{[1-(2-Amino-acetyl)-piperidin-4-yl-sulfanyl)]-acetyl}-12-[(4-aminomethyl-benzylamino)-ethyl]mutilin,

12-epi-12-desvinyl-14-O-[5-Hydroxymethyl-pyridin-2-yl-sulfanylacetyl]-12-[(4-aminomethyl-3-fluoro-benzylamino)-ethyl]mutilin,

12-epi-12-desvinyl-14-O-{4-[(2-Amino-acetylamino)-cyclohexylsulfanyl]-acetyl}-12-[(4-aminomethyl-3-fluoro-benzylamino)-ethyl]mutilin,

12-epi-12-desvinyl-14-O-{[1-(2-Amino-acetyl)-piperidin-4-yl-sulfanyl]-acetyl}-12-[(4-aminomethyl-3-fluoro-benzylamino)-ethyl]mutilin,

12-epi-12-desvinyl-14-O-[(5-Aminomethyl-pyridin-2-yl-sulfanyl)-acetyl]-12-[(4-aminomethyl-2,5-difluoro-benzylamino)-ethyl]mutilin,

12-epi-12-desvinyl-14-O-{[1-(2-Amino-acetyl)-piperidin-4-yl-sulfanyl]-acetyl}-12-[(4-aminomethyl-2,5-difluoro-benzylamino)-ethyl]mutilin,

12-epi-12-desvinyl-14-O-{[1-(2-Amino-acetyl)-piperidin-4-yl-sulfanyl]-acetyl}-12 {2-[4-(2-amino-ethoxy)-benzylamino]-ethyl}mutilin,

12-epi-12-desvinyl-14-O-{{4-[(2-Amino-acetylamino)-methyl]-cyclohexylsulfanyl}-acetyl}-12-[(4-aminomethyl-3-fluoro-benzylamino)-ethyl]mutilin,

12-epi-12-desvinyl-14-O-[(Azepan-4-ylsulfanyl)-acetyl]-12-[(4-aminomethyl-phenylamino)-ethyl]mutilin,

12-epi-12-desvinyl-14-O-{{4-[(2-Amino-acetylamino)]-cyclohexylsulfanyl}-acetyl}-12-[(4-aminomethyl-phenylamino)-ethyl]mutilin,

12-epi-12-desvinyl-14-O-{[1-(2-Amino-acetyl)-piperidin-4-yl-methylsulfanyl]-acetyl}-12-[(4-aminomethyl-phenylamino)-ethyl]mutilin,

12-epi-12-desvinyl-14-O-{[1-(2-Amino-acetyl)-piperidin-4-yl-sulfanyl]-acetyl}-12-(8-amino-octyl) mutilin,

12-epi-12-desvinyl-14-O-{[1-(2-Amino-acetyl)-piperidin-4-yl-sulfanyl]-acetyl}-12-[3-(4-aminomethyl-phenyl)-propyl]mutilin,

12-epi-12-desvinyl-14-O-[(Azepan-4-yl-sulfanyl)-acetyl]-12-[3-(4-aminomethyl-phenyl)-propyl]mutilin,

12-epi-12-desvinyl-14-O-[(Azepan-4-yl-sulfanyl)-acetyl]-12-(6-aminohexyl) mutilin,

12-epi-12-desvinyl-14-O-[(Azepan-4-yl-sulfanyl)-acetyl]-12-(8-amino-octyl) mutilin,

12-epi-12-desvinyl-14-O-{{4-[(2-Amino-acetylamino)-methyl]-cyclohexylsulfanyl}-acetyl}-12-[2-{4-[(2-amino-ethylamino)-methyl]-phenyl}-ethenyl) mutilin,

12-epi-12-desvinyl-14-O-{{4-[(2-Amino-acetylamino)-methyl]-cyclohexylsulfanyl}-acetyl}-12-[2-{4-[(2-amino-ethylamino)-methyl]-phenyl}-ethyl) mutilin,

12-epi-12-desvinyl-14-O-[(Azepan-4-ylsulfanyl)-acetyl]-12-[2-(4-Aminomethyl-phenyl)-ethyl]-mutilin,

12-epi-12-desvinyl-14-O-[(Azepan-4-ylsulfanyl)-acetyl]-12-((E)-2-pyridin-3-yl-ethenyl) mutilin,

12-epi-12-desvinyl-14-O-[(Azepan-4-ylsulfanyl)-acetyl]-12-((E)-2-{4-[(2-Amino-ethylamino)-methyl]-phenyl}-ethenyl) mutilin,

12-epi-12-desvinyl-14-O-[(Azepan-4-ylsulfanyl)-acetyl]-12-[2-{4-[(2-amino-ethylamino)-methyl]-phenyl}-ethyl) mutilin,

12-epi-12-desvinyl-14-O-[(Azepan-4-ylsulfanyl)-acetyl]-12-((E)-2-{4-[(2-amino-ethylamino)-methyl]-3-fluoro-phenyl}-ethenyl) mutilin,

12-epi-14-O-{[1-(2-Amino-acetyl)-piperidin-4-yl-sulfanyl]-acetyl}-12-((E)-2-{4-[(2-amino-ethylamino)-methyl]-phenyl}-ethenyl) mutilin,

12-epi-14-O-{[1-(2-Amino-acetyl)-piperidin-4-yl-sulfanyl]-acetyl}-12-[2-{4-[(2-amino-ethylamino)-methyl]-phenyl}-ethyl) mutilin,

12-epi-12-desvinyl-14-O-[(5-Aminomethyl-pyridin-2-ylsulfanyl)-acetyl]-12-[2-(4-aminomethyl-benzoylamino)-ethyl]mutilin,

12-epi-12-desvinyl-14-O-[(Piperidin-4-ylsulfanyl]-acetyl]-12-[2-(3-methyl-pyrazin-2-yl)-ethenyl]-mutilin, and their pharmaceutically acceptable salts or solvates.

18 . The method according to claim 8 , wherein the compound or the pharmaceutically acceptable salt or solvate thereof is 12-epi-12-desvinyl-14-O-[(Piperidin-4-ylsulfanyl]-acetyl]-12-[2-(3-methyl-pyrazin-2-yl)-ethenyl]-mutilin or its pharmaceutically acceptable salts or solvates.

19 . The method according to claim 8 , wherein the viral infection relates to a respiratory disease.

20 . The method according to claim 8 , wherein the viral infection relates to an acute respiratory syndrome optionally including Influenza, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) or COVID-19.

21 . The method according to claim 8 , the viral infection is associated with a virus being a positive- or negative-sense single-stranded RNA virus, optionally the virus is

Coronaviridae, optionally including human coronavirus,

Paramyxoviridae, optionally including Paramyxovirinae, optionally including Measles virus, or Pneumovirinae, optionally including Respiratory Syncytial Virus,

Orthomyxoviridae, optionally including Influenza virus,

Flaviviridae, optionally including Dengue virus or Zika virus, or

Picornaviridae, optionally including Rhinovirus.

22 . The method according to claim 8 , wherein the viral infection relates to an airborne disease.

Assignments (2)

Priority Claims (1)

Continuity (1)

References Cited (26)