Combination pharmaceutical agents as RSV inhibitors

Patent metadata

Field	Value
Publication number	US-12268694-B2
Application number	US-202017094029-A
Country	US
Kind code	B2
Filing date	Nov 10, 2020
Priority date	Sep 29, 2017
Publication date	Apr 8, 2025
Grant date	Apr 8, 2025

Abstract

The present invention relates to a pharmaceutical composition useful for treating a Respiratory Syncytial Virus (RSV) infection, comprising a compound which isor a pharmaceutically acceptable salt thereof, and a second anti-respiratory syncytial virus agent.

First claim

What is claimed:

1. A pharmaceutical composition comprising a compound which is

or a pharmaceutically acceptable salt thereof,
a second anti-respiratory syncytial virus agent; and
a pharmaceutically acceptable carrier or excipient.

2. The pharmaceutical composition of claim 1 , wherein the second anti-respiratory syncytial virus agent is selected from the group consisting of an anti-RSV antibody, a fusion protein inhibitor, an N-protein inhibitor, an RSV polymerase inhibitor, an IMPDH inhibitor, and an interferon.

3. The pharmaceutical composition of claim 2 , wherein the second anti-respiratory syncytial virus agent is selected from the group consisting of RSV-IGIV, palivizumab, motavizumab, MK-1654, 1-cyclopropyl-3-[[l-(4-hydroxybutyl)benzimidazol-2-yl]methyl]imidazo[4,5-c]pyridin-2-one (BMS-433771), 4,4″-bis-{4,6-bis-[3-(bis-carbamoylmethyl-sulfamoyl)-phenylamino]-(l,3,5)triazin-2-ylamino}-biphenyl-2,2″-di sulfonic-acid (RFI-641), 4,4′-Bis[4,6-di[3-aminophenyl-N,N-bis(2-carbamoylethyl)-sulfonilimino]-l,3,5-triazine-2-ylamino]-biphenyl-2,2′-disulfonic acid, disodium salt (CL387626), 2-[[2-[[l-(2-aminoethyl)-4-piperidinyl]amino]-4-methyl-lH-benzimidazol-l-yl]-6-methyl-3-pyridinol (JNJ-2408068), 2-[[6-[[[2-(3-Hydroxypropyl)-5-methylphenyl]amino]methyl]-2-[[3-(morpholin-4-yl)propyl]amino]benzimidazol-l-yl]methyl]-6-methylpyridin-3-ol (TMC-353121), 5,5′-bis[l-(((5-amino-lH-tetrazolyl)imino)methyl)]2,2′,4″-methylidynetrisphenol (VP-14637, MDT-637), N-(2-hydroxyethyl)-4-methoxy-N-methyl-3-(6-methyl-[l,2,4]triazolo[3,4-a]phthalazin-3-yl)benzenesulfonamide (P13), 2-((2-((1-(2-aminoethyl)piperidin-4-yl)amino)-4-methyl-1H-benzo[d]imidazol-1-yl)methyl)-6-methylpyridin-3-ol (R170591), l,4-bis(3-methylpyridin-4-yl)-l,4-diazepane (05), (R)-9b-(4-chlorophenyl)-l-(4-fluorobenzoyl)-2,3-dihydro-lH-imidazo[r,2′:l,2]pyrrolo[3,4-c]pyridin-5(9bH)-one (BTA9981), [2,2-bis(docosyloxyoxymethyl)propyl-5-acetaoamido-3,5-dideoxy-4,7,8,9-tetra-0-(sodium-oxysulfonyl)-D-glycero-D-galacto-2-nonulopyranosid]onate (MBX-300), BTA-C286, N-(2-((S)-2-(5-((S)-3-aminopyrrolidin-l-yl)-6-methylpyrazolo[l,5-a]pyrimidin-2-yl)piperidine-1-carbonyl)-4-chlorophenyl)methanesulfonamide (GS-5806), an anti-RSV nanobody, a peptide fusion inhibitor, (S)-l-(2-fluorophenyl)-3-(2-oxo-5-phenyl-2,3-dihydro-lH-benzo[e] [1,4]diazepin-3-yl)urea (RSV-604), STP-92, iKT-041, 6-{4-[(biphenyl-2-ylcarbonyl) amino]benzoyl}-N-cyclopropyl-5,6-dihydro-4H-thieno[3,2-d][l]benzazepine-2-carboxamide (YM-53403), N-cyclopropyl-5-(4-(2-(pyrrolidin-l-yl)benzamido)benzoyl)-5,6,7,10-tetrahydrobenzo[b]cyclopenta[d]azepine-9-carboxamide, 6-(4-(2-(2-oxa-7-azaspiro[3.5]nonan-7-yl)nicotinamido)benzoyl)-N-cyclopropyl-5,6-dihydro-4H-benzo[b]thieno[2,3-d]azepine-2-carboxamide,4-amino-8-(3-{[2-(3,4-dimethoxyphenyl)ethyl]amino}propyl)-6,6-dimethyl-2-(4-methyl-3-nitrophenyl)-1H-imidazo[4,5-h]-isoquinoline-7,9(6H,8H)-dione, AZ27, ribavirin, 5-ethynyl-l-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR), 4-hydroxy-3-beta-D-ribofuranosylpyrazole-5-carboxamide (pyrazofurin), 1-((2R,3R,4S,5R)-3,4-dihydroxy-5(hydroxymethyl)tetrahydrofuran-2-yl)-lH-l,2,4-triazole-3-carboximidamide (Taribavirin, viramidine), (2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-l-(2H)-y I)-2-(chloromethy I)-4-fluoro-2-((isobutyryloxy)methyl)tetrahydrofuran-3-yl isobutyrate, (2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1 (2H)-yl)-2-(chloromethyl)-4-fluoro-2(hydroxymethyl)tetrahydrofuran-3-yl isobutyrate, ((2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-l(2H)-yl)-2-(chloromethyl)-4-fluoro-3-hydroxytetrahydrofuran-2-yl) methyl triphosphate, 4-amino-1-((2R,3R,4R,5R)-5-(chloromethyl)-3-fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(lH)-one, 1,3,4-thiadiazol-2-ylcyanamide (LY253963), tetrahydrofuran-3-yl-3-(3-(3-methoxy-4-(oxazol-5-yl)phenyl)ureido)benzylcarbamate (VX-497), (4E)-6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid (Mycophenolic acid), 2-morpholin-4-ylethyl-(E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-lH-2-benzofuran-5-yl)-4-methylhex-4-enoate (Mycophenolate Mofetil), a Type Iinterferon, a Type 2 interferon, a Type 3 interferon, a double stranded RNA oligonucleotide, 5-methyl-N-[4-(trifluoromethyl)phenyl]-isoxazole-4-carboxamide (leflumomide), N-(2-chloro-4-methylpheny I)-2-((1-(4-methoxypheny I)-lH-benzo[d]imidazol-2-yl)thio)propanamide (JMN3-003), an intratracheal formulation of recombinant human CClO (CG-100), high titer, human immunoglobulin (RI-001), a non-neutralizing mAb against the G protein (mAb 131-2G), ALN-RS VOI, ALN-RSV 02, Medi-559, Medi-534 and Medi-557, JNJ-53718678, AK-0529, RV521, BTA585, MIV-323, PC786, JNJ-64417184, ALS-8176, ALS-8112, ALX-0171, or a pharmaceutically acceptable salt of any of the foregoing.

4. The pharmaceutical composition of claim 1 wherein the second anti-respiratory syncytial virus agent is selected from the group consisting of ALS-8112, AZ-27, GS5806, and palivizumab.

Assignees

• Enanta Pharm Inc

Inventors

• Shook Brian C
• Kim In Jong
• Blaisdell Thomas P
• Yu Jianming
• Panarese Joseph
• Lin Kai
• Rhodin Michael H J
• Mcallister Nicole V
• Or Yat Sun

Classifications

• C07K16/11

  Paramyxoviridae (F); Pneumoviridae (F), e.g. respiratory syncytial virus [RSV] · CPC title

• A61P31/14

  for RNA viruses · CPC title

• C07D498/08

  Bridged systems · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title