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Disclosed herein are new antiviral compounds, together with pharmaceutical compositions that include one or more antiviral compounds, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a paramyxovirus viral infection with one or more small molecul

Disclosed herein are new antiviral compounds, together with pharmaceutical compositions that include one or more antiviral compounds, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a paramyxovirus viral infection with one or more small molecule compounds. Examples of paramyxovirus infection include an infection caused by human respiratory syncytial virus (RSV).

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1. A compound of Formula (I), or a pharmaceutically acceptable salt thereof, having the structure: A-L-Y  (I)wherein: L is selected from the group consisting of: A is selected from the group consisting of an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally sub

1. A compound of Formula (I), or a pharmaceutically acceptable salt thereof, having the structure: A-L-Y  (I)wherein: L is selected from the group consisting of: A is selected from the group consisting of an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted aryl, an optionally substituted aryl(C1-2 alkyl), an optionally substituted heteroaryl and an optionally substituted heterocyclyl;Y is selected from the group consisting of an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted aryl, an optionally substituted heteroaryl and an optionally substituted heterocyclyl;R1b, R1c and R1d are each independently hydrogen or an unsubstituted C1-4 alkyl;R2b, R2b1, R2c, R2c1, R2d and R2d1 are each independently selected from the group consisting of hydrogen, an optionally substituted C1-4 alkyl, an optionally substituted aryl(C1-6 alkyl), an optionally substituted heterocyclyl(C1-6 alkyl), an alkoxyalkyl, an aminoalkyl, a hydroxyalkyl and hydroxy; orR2b1 is hydrogen, and R1b and R2b are joined together with the atoms to which they are attached to form an optionally substituted 5 membered heterocyclyl or an optionally substituted 6 membered heterocyclyl;X1b, X2b and X3b are each independently C, N, O or C(═O), and form a bi-cyclic ring selected from an optionally substituted bi-cyclic heteroaryl and an optionally substituted bi-cyclic heterocyclyl by joining X1b and X3b together, wherein between X1b and X2b represents a single or double bond between X1b and X2b; between X2b and X3b represents a single or double bond between X2b and X3b; and provided that at least one of X1b, X2b and X3b comprises a nitrogen atom and both cannot be double bonds; with the proviso that the valencies of X1b, X2b and X3b can be each independently satisfied with a substituent selected from hydrogen and an optionally substituted C1-4 alkyl; and X1b, X2b and X3b are uncharged;R3c and R3c1 are each independently selected from the group consisting of hydrogen, hydroxy, halogen, amino, an optionally substituted C1-4 alkyl, an optionally substituted C2-4 alkenyl, an optionally substituted C2-4 alkynyl, an optionally substituted C3-6 cycloalkyl, an optionally substituted C1-4 alkoxy, —O-carboxy, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, CHF2, CF3 and provided that R3c and R3c1 cannot be both hydrogen; or R3c and R3c1 together form ═N—ORc; or R3c and R3c1 together with the atom to which they are attached can be joined to form an optionally substituted 3 membered ring, an optionally substituted 4 membered ring, an optionally substituted 5 membered ring or an optionally substituted 6 membered ring; is hydrogen or an unsubstituted C1-4 alkyl;R4c and R5c are taken together to form an unsubstituted aryl, an unsubstituted heteroaryl or an optionally substituted heterocyclyl;Zc is N or CH;md is 0 or 1; andring Bd is an optionally substituted C5 cycloalkyl;ring Bd1 is an optionally substituted pyridinyl; andprovided that when L is Formula (IIc), then Y is absent. 2-53. (canceled) 54. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein L is Formula (Ib): 55-59. (canceled) 60. The compound of claim 54, or a pharmaceutically acceptable salt thereof, wherein the bi-cyclic ring is an optionally substituted an optionally substituted an optionally substituted and an optionally substituted wherein each ----- is independently absent or a bond; each RB1, each RB2 and each RB3 is an unsubstituted C1-6 alkyl, halogen, hydroxy, amino, mono-substituted amino, di-substituted amino or —NH—S(═O)C1-4 alkyl; and RB4 is hydrogen or an unsubstituted C1-6 alkyl. 61. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein L is Formula (Ib1): wherein: the dashed semi-circle along with the two carbon atoms to which it is connected form an optionally substituted cycloalkenyl an optionally substituted aryl, an optionally substituted heteroaryl or an optionally substituted heterocyclyl; and R4b3 is selected from the group consisting of hydrogen, halogen, hydroxy, an optionally substituted C1-8 alkyl, an optionally substituted C2-8 alkenyl, an optionally substituted C2-8 alkynyl, an optionally substituted C3-6 cycloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, an optionally substituted hydroxyalkyl, an optionally substituted C1-8 alkoxy, an optionally substituted alkoxyalkyl, amino, mono-substituted amino, di-substituted amino, halo(C1-8 alkyl), haloalkyl and an optionally substituted C-carboxy. 62-65. (canceled) 66. The compound of claim 54, or a pharmaceutically acceptable salt thereof, wherein R1b is hydrogen. 67. The compound of claim 54, or a pharmaceutically acceptable salt thereof, wherein R1b is unsubstituted C1-4 alkyl. 68. The compound of claim 54, or a pharmaceutically acceptable salt thereof, wherein R2b and R2b1 are both hydrogen. 69-73. (canceled) 74. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein L is Formula (Ic): 75-94. (canceled) 95. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein L is Formula (Id): 96-104. (canceled) 105. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein A is an optionally substituted aryl. 106. The compound of claim 105, or a pharmaceutically acceptable salt thereof, wherein A is an optionally substituted phenyl. 107. The compound of claim 106, or a pharmaceutically acceptable salt thereof, wherein A is a phenyl substituted with one or more substituents selected from the group consisting of: an unsubstituted C1-4 alkyl, an optionally substituted C1-4 alkyl, cycloalkyl, hydroxy, an optionally substituted C1-4 alkoxy, C1-4 alkoxy, halogen, haloalkyl, an optionally substituted haloalkoxy, nitro, amino, mono-substituted amino, di-substituted amine, —O-amido, sulfenyl, alkyoxyalkyl, an optionally substituted aryl, an optionally substituted mono-cyclic heteroaryl, an optionally substituted mono-cyclic heterocyclyl, an optionally substituted aryl(C1-4 alkyl), an optionally substituted monocyclic heteroaryl(C1-4 alkyl), an optionally substituted monocyclic heterocyclyl(C1-4 alkyl), hydroxyalkyl and aminoalkyl. 108. The compound of claim 106, or a pharmaceutically acceptable salt thereof, wherein A is a phenyl substituted with one or more substituents selected from the group consisting of: methyl, ethyl, propyl, butyl, hydroxy, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, t-butoxy, phenoxy, bromo, chloro, fluoro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, cyano, N,N-di-methyl-amine, N,N-di-ethyl-amine, N-methyl-N-ethyl-amine, N-methyl-amino, N-ethyl-amino, amino, N-amido, N-sulfonamido, alkylthio, an optionally substituted phenyl, an optionally substituted imidazole, an optionally substituted morpholinyl, an optionally substituted pyrazole, an optionally substituted pyrrolidinyl, an optionally substituted pyridinyl, an optionally substituted piperidinyl, an optionally substituted piperidinone, an optionally substituted pyrrolidinone, an optionally substituted pyrimidine, an optionally substituted pyrazine, an optionally substituted 1,2,4-oxadiazole, —(CH2)1-4—OH, —(CH2)1-2—NH(CH3), an optionally substituted —(CH2)1-2-imidazole, an optionally substituted —(CH2)1-2-pyrrolidinone, an optionally substituted —(CH2)1-2-imidazolidinone, —O(CH2)2—NH2, —O(CH2)2—NH(CH3), —O(CH2)2—N(CH3)2, —O—(CH2)2-4OH, —O(CH2)2OCH3, an optionally substituted —O(CH2)0-2-cyclopentanone, an optionally substituted —O(CH2)0-2pyrrolidinone, an optionally substituted —O(CH2)0-2-morpholinyl, an optionally substituted —O(CH2)0-2-triazole, an optionally substituted —O(CH2)0-2-imidazole, an optionally substituted —O(CH2)0-2-pyrazole, an optionally substituted —O(CH2)0-2-tetrahydrofuran, an optionally substituted —O(CH2)0-2-pyrrolidinone, an optionally substituted —O(CH2)0-2-tetrazole, an optionally substituted —O(CH2)0-2-tetrazolone, 109. The compound of claim 106, or a pharmaceutically acceptable salt thereof, wherein A is a di-substituted phenyl. 110-115. (canceled) 116. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Y is an optionally substituted aryl. 117. The compound of claim 116, or a pharmaceutically acceptable salt thereof, wherein Y is a mono-substituted phenyl. 118. The compound of claim 117, or a pharmaceutically acceptable salt thereof, wherein Y is a di-substituted phenyl. 119-126. (canceled) 127. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Y is unsubstituted. 128. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Y is substituted with one or more RB, wherein each RB is independently selected from the group consisting of: cyano, halogen, an optionally substituted C1-4 alkyl, an unsubstituted C2-4 alkenyl, an unsubstituted C2-4 alkynyl, an optionally substituted aryl, an optionally substituted 5 or 6 membered heteroaryl, an optionally substituted 5 or 6 membered heterocyclyl, hydroxy, C1-4 alkoxy, alkoxyalkyl, C1-4 haloalkyl, haloalkoxy, an unsubstituted acyl, an optionally substituted —C-carboxy, an optionally substituted —C-amido, sulfonyl, carbonyl, amino, mono-substituted amine, di-substituted amine and 129. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Y is an optionally substituted benzothiophene. 130. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Y is an optionally substituted benzofuran or an optionally substituted indole. 131. (canceled) 132. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) is selected from the group consisting of: or a pharmaceutically acceptable salt of the foregoing. 133. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) is selected from the group consisting of: or a pharmaceutically acceptable salt of the foregoing. 134. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) is selected from the group consisting of: or a pharmaceutically acceptable salt of the foregoing. 135. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) is selected from the group consisting of: or a pharmaceutically acceptable salt of the foregoing. 136. A pharmaceutical composition comprising an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, excipient, or combination thereof. 137-143. (canceled) 144. A method of ameliorating or treating a paramyxovirus infection, comprising administering to a subject suffering from the paramyxovirus infection an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof. 145. A method of ameliorating or treating a paramyxovirus infection, comprising contacting a cell infected with the paramyxovirus with an effective amount of a compounds of claim 1, or a pharmaceutically acceptable salt thereof. 146. The method of claim 144, wherein the paramyxovirus infection is a human respiratory syncytial virus infection. 147. A method for inhibiting viral replication of a paramyxovirus, comprising contacting a cell infected with the virus with an effective amount of one or more compounds of claim 1, or a pharmaceutically acceptable salt thereof. 148. The method of claim 147, further comprising contacting the cell with an effective amount with one or more additional agents, wherein the one or more additional anti-RSV agents is selected from the group consisting of an anti-RSV antibody, a fusion protein inhibitor, an N-protein inhibitor, a RSV polymerase inhibitor, an IMPDH inhibitor, an interferon and another compound that inhibits the RSV virus, or a pharmaceutically acceptable salt of any of the foregoing. 149. The method of claim 148, wherein the one or more additional agents is selected from the group consist of RSV-IGIV, palivizumab, motavizumab, 1-cyclopropyl-3-[[1-(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]-(1,3,5)triazin-2-ylamino}-biphenyl-2,2″-disulfonic-acid (RFI-641), 4,4′-Bis[4,6-di[3-aminophenyl-N,N-bis(2-carbamoylethyl)-sulfonilimino]-1,3,5-triazine-2-ylamino]-biphenyl-2,2′-disulfonic acid, disodium salt (CL387626), 2-[[2-[[1-(2-aminoethyl)-4-piperidinyl]amino]-4-methyl-1H-benzimidazol-1-yl]-6-methyl-3-pyridinol (JNJ-2408068), 2-[[6-[[[2-(3-Hydroxypropyl)-5-methylphenyl] amino] methyl]-2-[[3-(morpholin-4-yl)propyl]amino]benzimidazol-1-yl]methyl]-6-methylpyridin-3-ol (TMC-353121), 5,5′-bis[1-(((5-amino-1H-tetrazolyl)imino)methyl)]2,2′,4″-methylidynetrisphenol (VP-14637, MDT-637), N-(2-hydroxyethyl)-4-methoxy-N-methyl-3-(6-methyl-[1,2,4]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), 1,4-bis(3-methylpyridin-4-yl)-1,4-diazepane (C15), (R)-9b-(4-chlorophenyl)-1-(4-fluorobenzoyl)-2,3-dihydro-1H-imidazo[1′,2′: 1,2]pyrrolo[3,4-c]pyridin-5(9bH)-one (BTA9981), [2,2-bis(docosyloxy-oxymethyl)propyl-5-acetaoamido-3,5-dideoxy-4,7,8,9-tetra-O-(sodium-oxysulfonyl)-D-glycero-D-galacto-2-nonulopyranosid]onate (MBX-300), BTA-C286, N-(2-((S)-2-(5-((S)-3-aminopyrrolidin-1-yl)-6-methylpyrazolo[1,5-a]pyrimidin-2-yl)piperidine-1-carbonyl)-4-chlorophenyl)methanesulfonamide (GS-5806), an anti-RSV nanobody, a peptide fusion inhibitor, a peptide having the sequence FDASISQVNEKINQSLAFIRKSDELLHNVNAGKST (T-118), (S)-1-(2-fluorophenyl)-3-(2-oxo-5-phenyl-2,3-dihydro-1H-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][1]benzazepine-2-carboxamide (YM-53403), N-cyclopropyl-5-(4-(2-(pyrrolidin-1-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-1-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)-1H-1,2,4-triazole-3-carboximidamide (Taribavirin, viramidine), 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-1H-2-benzofuran-5-yl)-4-methylhex-4-enoate (Mycophenolate Mofetil), a Type 1 interferon, 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-methylphenyl)-2-((1-(4-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)thio)propanamide (JMN3-003), an intratracheal formulation of recombinant human CC10 (CG-100), high titer, human immunoglobulin (RI-001), a non-neutralizing mAb against the G protein (mAb 131-2G), ALN-RSV01, ALN-RSV02, Medi-559, Medi-534 and Medi-557, or a pharmaceutically acceptable salt of any of the foregoing.