Use of nucleoside analog in preparation of drug for treating or preventing diseases caused by paramyxoviridae virus infections

Abstract

The present invention relates to use of a nucleoside analog in the preparation of a drug for treating or preventing diseases caused by Paramyxoviridae virus infections, and particularly relates to use of a compound represented by formula I in combating Paramyxoviridae virus infections. The compound represented by formula I can efficiently inhibit the replication of Paramyxoviridae viruses, has low toxicity, small side effects, high oral bioavailability, and good drug developability, and can be used for treating diseases caused by Paramyxoviridae virus infections, especially diseases caused by human metapneumoviruses, human parainfluenza virus, and canine distemper virus.

Description

Application of nucleoside analogs in the preparation of drugs for the treatment or prevention of diseases caused by paramyxoviridae virus infections Technical Field

[0001] This invention relates to a novel use of a nucleoside analogue, and more specifically, to the use of a nucleoside analogue of formula (I) or a pharmaceutically acceptable salt thereof, and combinations thereof, in the preparation of medicaments for the prevention or treatment of diseases caused by paramyxoviridae virus infections. Background Technology

[0002] Paramyxoviridae is a family of viruses that includes many important species that infect a wide range of animals, including humans, birds, and mammals. Viruses in this family are typically highly infectious and can cause severe respiratory, nervous, and immune system diseases. Representative members of this family include respiratory syncytial virus (RSV), metapneumovirus, parainfluenza virus, measles virus, mumps virus, Nipah virus, Hendra virus, Newcastle disease virus, peste des petits ruminants virus (PPR), canine distemper virus, and duck plague virus.

[0003] Metapneumovirus (MPV) is a group of enveloped, negative-sense RNA viruses widely distributed in nature, infecting various hosts, including humans and animals. Depending on the host, metapneumoviruses can be divided into two main types: avian metapneumovirus (AMPV) and human metapneumovirus (HMPV). HMPV is the primary pathogen infecting humans, especially children, the elderly, and those with weakened immune systems. Infection with HMPV is seasonal, typically peaking in winter and spring. Infected patients may experience mild upper respiratory symptoms (such as cough and runny nose) or severe lower respiratory illnesses (such as bronchitis and pneumonia). HMPV is highly contagious and spreads through droplets.

[0004] Parainfluenza viruses (PIVs) are a group of enveloped, negative-sense RNA viruses widely distributed in nature, infecting various mammalian and avian hosts. Depending on the host, parainfluenza viruses are classified into several types, including human parainfluenza virus (HPIV) which infects humans and bovine parainfluenza virus (BPIV) which infects cattle. Parainfluenza viruses primarily infect respiratory tissues, causing acute respiratory infections with symptoms ranging from mild cough and nasal congestion to severe pneumonia. Human parainfluenza virus (HPIV) is a type of parainfluenza virus that specifically infects humans and is one of the important pathogens causing acute respiratory infections, posing a significant threat, especially to infants, the elderly, and immunocompromised individuals. HPIVs are classified into four types (HPIV-1 to HPIV-4) based on their antigenic characteristics. HPIV-1 and HPIV-2 typically cause laryngitis, manifesting as acute laryngotracheobronchitis, which is highly prevalent in infants and young children; HPIV-3 is closely associated with the occurrence of bronchitis and pneumonia; HPIV-4 is relatively rare and usually causes mild upper respiratory tract infections. HPIVs are transmitted through droplets and close contact and have a strong transmissibility.

[0005] Canine distemper virus is an RNA virus that primarily infects dogs, but can also affect some wild animals. Canine distemper is a fatal disease, typically manifesting as high fever, respiratory symptoms, neurological damage, and immunosuppression, especially severe in puppies, and spreads rapidly in unvaccinated dog populations.

[0006] Currently, there are no specific antiviral drugs or vaccines for the vast majority of paramyxoviridae virus infections, and treatment is mainly symptomatic and supportive. Therefore, developing safe, effective, and easy-to-use antiviral drugs is of great significance for reducing the burden of these virus-related diseases, especially convenient oral medications. Summary of the Invention

[0007] To address the aforementioned problems, this invention provides a class of drugs for the prevention and / or treatment of diseases related to paramyxoviridae virus infection. These drugs have significant anti-paramyxoviridae virus activity and high oral bioavailability, and can be used for the prevention and / or treatment of diseases caused by paramyxoviridae viruses.

[0008] According to one aspect of the present invention, the use of a compound of formula I or a stereoisomer thereof, a solvate, a prodrug, a stable isotopic derivative thereof or a pharmaceutically acceptable salt thereof in the preparation of an inhibitor for inhibiting the replication of paramyxoviridae viruses is provided.

[0009] in,

[0010] R1 is selected from hydrogen, substituted or unsubstituted C. 1-20 Alkyl group, substituted or unsubstituted C 3-10 Cycloalkylformyl group, wherein the substitution is performed by one or more Q1 groups;

[0011] R2 is selected from hydrogen, substituted or unsubstituted C. 1-20 Alkyl group, substituted or unsubstituted C 3-10 Cycloalkylformyl group, wherein the substitution is performed by one or more Q2 groups;

[0012] Alternatively, R1 and R2 can be connected to form a...

[0013] R3 is selected from hydrogen, substituted or unsubstituted C. 1-20 Alkyl group, substituted or unsubstituted C 3-10 Cycloalkylformyl group, wherein the substitution is performed by one or more Q3 groups;

[0014] Q1, Q2, and Q3 are each independently selected from cyano, amino, hydroxyl, and halogen groups;

[0015] R4 is selected from hydrogen, deuterium, cyano, amino, hydroxyl, and halogen.

[0016] In some embodiments, R1 in Formula I is selected from hydrogen, and Q1 is substituted or unsubstituted C. 1-18 Alkyl group, Q1 substituted or unsubstituted C 3-7 Cycloalkylformyl group.

[0017] In some embodiments, R1 in Formula I is selected from hydrogen, and Q1 is substituted or unsubstituted C. 1-18 Alkyl group, Q1 substituted or unsubstituted C 3-6 Cycloalkylformyl group.

[0018] In some embodiments, R1 in Formula I is selected from hydrogen, formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, 2-aminoisovaleryl, pterovaleryl, hexanoyl, 2-ethylbutyryl, 3,3-dimethylbutyryl, heptayl, octanoyl, 2-propylvaleryl, nonanoyl, decanoyl, C 13 Alkyl group, C 14 Alkyl group, C 15 Alkyl group, C 16 Alkyl group, C 17 Alkyl group, C 18 Alkyl, cyclopropylformyl, cyclobutylformyl, cyclopentylformyl, and cyclohexylformyl, particularly selected from hydrogen, acetyl, propionyl, isobutyryl, 2-aminoisovaleryl, pivaloyl, 2-ethylbutyryl, 3,3-dimethylbutyryl, 2-propylvaleryl, C 13 Alkyl group, C15 Alkyl group, C 17 Alkyl group.

[0019] In some embodiments, Q1 is selected from amino, hydroxyl, and halogen.

[0020] In some embodiments, Q1 is selected from amino and halogen.

[0021] In some embodiments, Q1 is an amino group.

[0022] In some embodiments, R2 in Formula I is selected from hydrogen, Q2-substituted or unsubstituted C. 1-18 Alkyl group, Q2 substituted or unsubstituted C 3-7 Cycloalkylformyl group.

[0023] In some embodiments, R2 in Formula I is selected from hydrogen, Q2-substituted or unsubstituted C. 1-18 Alkyl group, Q2 substituted or unsubstituted C 3-6 Cycloalkylformyl group.

[0024] In some embodiments, R2 in Formula I is selected from hydrogen, formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, 2-aminoisovaleryl, pterovaleryl, hexanoyl, 2-ethylbutyryl, 3,3-dimethylbutyryl, heptanoyl, octanoyl, 2-propylvaleryl, nonanoyl, decanoyl, C 13 Alkyl group, C 14 Alkyl group, C 15 Alkyl group, C 16 Alkyl group, C 17 Alkyl group, C 18 Alkyl, cyclopropylformyl, cyclobutylformyl, cyclopentylformyl, and cyclohexylformyl, particularly selected from hydrogen, acetyl, propionyl, isobutyryl, 2-aminoisovaleryl, pivaloyl, 2-ethylbutyryl, 3,3-dimethylbutyryl, 2-propylvaleryl, C 13 Alkyl group, C 15 Alkyl group, C 17 Alkyl group.

[0025] In some embodiments, Q2 is selected from amino, hydroxyl, and halogen.

[0026] In some embodiments, Q2 is selected from amino and halogen.

[0027] In some embodiments, Q2 is an amino group.

[0028] In some embodiments, R1 and R2 in Formula I are not both hydrogen.

[0029] In some embodiments, R3 in Formula I is selected from hydrogen, Q3-substituted or unsubstituted C. 1-18 Alkyl group, Q3 substituted or unsubstituted C 3-7 Cycloalkylformyl group.

[0030] In some embodiments, R3 in Formula I is selected from hydrogen, Q3-substituted or unsubstituted C. 1-18 Alkyl group, Q3 substituted or unsubstituted C 3-6 Cycloalkylformyl group.

[0031] In some embodiments, R3 in Formula I is selected from hydrogen, formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, 2-aminoisovaleryl, pterovaleryl, hexanoyl, 2-ethylbutyryl, 3,3-dimethylbutyryl, heptayl, octanoyl, 2-propylvaleryl, nonanoyl, decanoyl, C 13 Alkyl group, C 14 Alkyl group, C 15 Alkyl group, C 16 Alkyl group, C 17 Alkyl group, C 18 Alkyl, cyclopropylformyl, cyclobutylformyl, cyclopentylformyl, and cyclohexylformyl, particularly selected from hydrogen, acetyl, propionyl, isobutyryl, 2-aminoisovaleryl, pivaloyl, 2-ethylbutyryl, 3,3-dimethylbutyryl, 2-propylvaleryl, C 13 Alkyl group, C 15 Alkyl group, C 17 Alkyl group.

[0032] In some embodiments, Q3 is selected from amino, hydroxyl, and halogen.

[0033] In some embodiments, Q3 is selected from amino and halogen.

[0034] In some embodiments, Q3 is an amino group.

[0035] In some embodiments, R4 in Formula I is selected from hydrogen, deuterium, and halogens.

[0036] In some embodiments, R4 in Formula I is selected from hydrogen, deuterium, fluorine, chlorine and iodine.

[0037] In a specific embodiment, R1, R2, and R3 in Formula I are each independently selected from hydrogen, acetyl, propionyl, isobutyryl, and 2-ethylbutyryl.

[0038] Alternatively, R1 and R2 can be connected to form a...

[0039] R4 is selected from hydrogen and deuterium.

[0040] In some embodiments, the compound represented by Formula I is selected from any of the following:

[0041] On the other hand, the present invention provides the use of a compound of Formula I or a stereoisomer thereof, a solvate, a prodrug, a stable isotope derivative thereof or a pharmaceutically acceptable salt thereof in inhibiting the replication of paramyxoviridae viruses, wherein the compound of Formula I and its substituents are as described above.

[0042] On the other hand, the present invention provides the use of a compound of Formula I or a stereoisomer thereof, a solvate, a prodrug, a stable isotope derivative thereof or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating and / or preventing or alleviating diseases caused by infection with paramyxoviridae viruses, wherein the compound of Formula I and its substituents are as described above.

[0043] On the other hand, the present invention provides the use of a compound of Formula I or a stereoisomer thereof, a solvate, a prodrug, a stable isotope derivative thereof or a pharmaceutically acceptable salt thereof in the treatment and / or prevention and relief of diseases caused by infection with paramyxoviridae viruses, wherein the compound of Formula I and its substituents are as described above.

[0044] On the other hand, the present invention provides the use of a pharmaceutical composition comprising a compound of Formula I and / or its stereoisomers, solvates, prodrugs, stable isotope derivatives or pharmaceutically acceptable salts thereof in the preparation of an inhibitor for inhibiting the replication of paramyxoviridae viruses, wherein the compound of Formula I and its substituents are as described above.

[0045] On the other hand, the present invention provides the use of a pharmaceutical composition comprising a compound of Formula I and / or its stereoisomers, solvates, prodrugs, stable isotope derivatives or pharmaceutically acceptable salts thereof in the preparation of a medicament for treating and / or preventing or alleviating diseases caused by infection with paramyxoviridae viruses, wherein the compound of Formula I and its substituents are as described above.

[0046] In some embodiments, the paramyxoviridae virus is selected from metapneumovirus, parainfluenza virus, measles virus, mumps virus, Nipah virus, Hendra virus, Newcastle disease virus, peste des petits ruminants virus, canine distemper virus, and duck plague virus.

[0047] In some embodiments, the paramyxoviridae virus is selected from metapneumovirus, parainfluenza virus, canine distemper virus, measles virus, mumps virus, Nipah virus, and Hendra virus.

[0048] In some embodiments, the paramyxoviridae virus is selected from metapneumovirus, parainfluenza virus, and canine distemper virus.

[0049] In some embodiments, the diseases associated with infection by paramyxoviridae viruses are selected from the group consisting of:

[0050] (1) Common cold, high-risk symptom infection, respiratory tract infection, bronchitis, pneumonia and its complications caused by metapneumovirus infection;

[0051] (2) Common cold, high-risk symptom infection, respiratory tract infection, bronchitis, pneumonia and their complications caused by parainfluenza virus infection;

[0052] (3) Measles, common cold, high-risk symptom infection, respiratory infection, bronchitis, pneumonia and their complications caused by measles virus infection;

[0053] (4) High-risk symptoms of mumps virus infection, including mumps, orchitis, meningitis, bronchitis, pneumonia and its complications;

[0054] (5) High-risk symptoms of Nipah virus infection, including respiratory infections, encephalitis, pneumonia and its complications;

[0055] (6) High-risk symptomatic infections, encephalitis, pneumonia and their complications caused by Hendra virus infection;

[0056] (7) Newcastle disease caused by Newcastle disease virus infection and its complications;

[0057] (8) Peste des petits ruminants (PPR) virus infection and its complications;

[0058] (9) Canine distemper caused by canine distemper virus infection and its complications;

[0059] (10) Duck plague virus infection causes duck plague and its complications;

[0060] (11) Any combination of the above diseases.

[0061] In some embodiments, the diseases associated with infection by paramyxoviridae viruses are selected from the group consisting of:

[0062] (1) Common cold, high-risk symptom infection, respiratory tract infection, bronchitis, pneumonia and its complications caused by metapneumovirus infection;

[0063] (2) Common cold, high-risk symptom infection, respiratory tract infection, bronchitis, pneumonia and their complications caused by parainfluenza virus infection;

[0064] (3) Measles, common cold, high-risk symptom infection, respiratory infection, bronchitis, pneumonia and their complications caused by measles virus infection;

[0065] (4) High-risk symptoms of mumps virus infection, including mumps, orchitis, meningitis, bronchitis, pneumonia and its complications;

[0066] (5) High-risk symptoms of Nipah virus infection, including respiratory infections, encephalitis, pneumonia and its complications;

[0067] (6) High-risk symptomatic infections, encephalitis, pneumonia and their complications caused by Hendra virus infection;

[0068] (7) Canine distemper caused by canine distemper virus infection and its complications;

[0069] (8) Any combination of the above diseases.

[0070] In some embodiments, the diseases associated with infection by paramyxoviridae viruses are selected from the group consisting of:

[0071] (1) Common cold, high-risk symptom infection, respiratory tract infection, bronchitis, pneumonia and its complications caused by metapneumovirus infection;

[0072] (2) Common cold, high-risk symptom infection, respiratory tract infection, bronchitis, pneumonia and their complications caused by parainfluenza virus infection;

[0073] (3) Canine distemper caused by canine distemper virus infection and its complications;

[0074] (4) Any combination of the above diseases.

[0075] In some embodiments, the pharmaceutical composition comprises at least one of the aforementioned compounds or their stereoisomers, solvates, hydrates, prodrugs, stable isotope derivatives and their pharmaceutically acceptable salts, as well as pharmaceutically acceptable carriers, diluents or excipients.

[0076] In some embodiments, the pharmaceutical composition further comprises other antiviral agents selected from the group consisting of: PF-07321332 (Nirmatrelvir), S-217622 (Ensitrelvir), FHPI (4-[4-(4-fluorophenyl)-5-pyridin-4-yl-1,3-dihydro-imidazol-2-yl]cyclohexyl-2,5-dien-1-one), aloxistatin, conivaptan, favipiravir, Galidesivir, and NHC (EIDD). -1931), EIDD-2801, GC-376, Lopinavir, Ritonavir, Nelfinavir; Chloroquine, Hydroxychloroquine, Cyclosporine, Carrimycin, Baicalin, Baicalein, Forsythoside, Chlorogenic acid acid), emodin, mycophenolic acid, mycophenolate mofetil, naphthoquine, ciclesonide, ribavirin, penciclovir, leflunomide, teriflunomide, nafamostat, nitazoxanide, darunavir, arbidol, carmostat, niclosamide, baricitinib, ruxolitinib, dasatinib, saquinavir, beclabuvir, simeprevir, palilizumab, motavizumab, RSV-IGIV MEDI557, A-60444 (RSV-604), MDT-637, BMS-433771, or pharmaceutically acceptable salts thereof, or combinations thereof.

[0077] In some embodiments, the pharmaceutical composition further comprises one or more other antiviral drugs selected from the group consisting of: PF-07321332 (Nirmatrelvir), S-217622 (Ensitrelvir), FHPI (4-[4-(4-fluorophenyl)-5-pyridin-4-yl-1,3-dihydro-imidazol-2-yl]cyclohexyl-2,5-dien-1-one), aloxistatin, conivaptan, favipiravir, NHC (EIDD-1931), EIDD-2801, baicalin, baicalein, forsythoside, chlorogenic acid, emodin, glycyrrhizic acid, chloroquine, hydroxychloroquine, and nelfinavir.

[0078] In some embodiments, the pharmaceutical composition further comprises other antiviral drugs selected from the group consisting of: interferon, RNA-dependent RNA polymerase inhibitors (such as favipiravir, Galidesivir, NHC (EIDD-1931), EIDD-2801), 3CL protease inhibitors (such as GC-376), lopinavir, ritonavir, nelfinavir, S-217622 (Ensitrelvir), PF-07321332 (Nirmatrelvir); chloroquine, hydroxychloroquine, cyclosporine, carrimycin, baicalin, baicalein, forsythoside, chlorogenic acid, emodin, and mycophenolic acid. cid), Mycophenolate mofetil, Naphthoquine, Ciclesonide, Ribavirin, Penciclovir, Leflunomide, Teriflunomide, Nafamostat, Nitazoxanide, Darunavir, Arbidol, Camostat, Niclosamide, Baricitinib, Rucote Ruxolitinib, dasatinib, saquinavir, beclabuvir, simeprevir, palizumab, motavizumab, RSV-IGIVMEDI-557, A-60444 (RSV-604), MDT637, BMS-433771, FHPI (4-[4-(4-fluorophenyl)-5-pyridin-4-yl-1,3-dihydro-imidazol-2-yl]cyclohexyl-2,5-dien-1-one), aloxistatin, conivaptan, or pharmaceutically acceptable salts thereof, or combinations thereof.

[0079] In some embodiments, the pharmaceutical composition further comprises other drugs selected from the group consisting of: zinc, fingolimod, vitamin C, olmesartan medoxomil, valsartan, losartan, thalidomide, glycyrrhizic acid, artemisinin, dihydroartemisinin, artesunate, artemisone, azithromycin, escin, naproxen, or combinations thereof.

[0080] In some embodiments, the pharmaceutical composition further comprises other drugs selected from the group consisting of: (Y1) RNA replicase inhibitors (such as favipiravir, Galidesivir, NHC, EIDD-2801); (Y2) lopinavir; (Y3) ritonavir; (Y4) chloroquine, hydroxychloroquine, or a pharmaceutically acceptable salt thereof (such as chloroquine phosphate); (Y5) nelfinavir; and (Y6) any combination of Y1 to Y5 above.

[0081] In some embodiments, the pharmaceutical composition further comprises other drugs selected from the group consisting of: interferon, RNA-dependent RNA polymerase inhibitors (such as favipiravir, Galidesivir, NHC, EIDD-2801); 3CL protease inhibitors (such as GC-376), lopinavir, ritonavir, nelfinavir; chloroquine, hydroxychloroquine, cyclosporine, carrimycin, baicalin, baicalein, forsythoside, chlorogenic acid, emodin, mycophenolic acid, and mycophenolate. mofetil, naphthoquine, ciclesonide, ribavirin, penciclovir, leflunomide, terifolium The interferons include nafamostat, nitazoxanide, darunavir, arbidol, carmostat, niclosamide, baricitinib, ruxolitinib, dasatinib, saquinavir, beclabuvir, simeprevir, palizumab, motavizumab, RSV-IGIVMEDI557, A-60444 (RSV-604), MDT-637, BMS-433771, or pharmaceutically acceptable salts thereof, or combinations thereof. The interferons include one or more of interferon α-2a, interferon α-2b, interferon α-n1, interferon α-n3, interferon β-1a, and interferon β-1b.

[0082] In some embodiments, the pharmaceutical composition further comprises one or more other drugs selected from the group consisting of: for example, the application of “anti-inflammatory signal transduction modulators” (referred to herein as AISTMs) such as phosphodiesterase inhibitors (e.g., PDE-4, PDE-5, or PDE-7 specific), transcription factor inhibitors (e.g., blocking NFκB via IKK inhibition), or kinase inhibitors (e.g., blocking P38MAP, JNK, PI3K, EGFR, or Syk) is a logical approach to cutting off inflammation because these small molecules target a limited number of common intracellular pathways—those signal transduction pathways that are key points of anti-inflammatory therapeutic intervention (see review by PJ Barnes, 2006). These non-restrictive additional therapeutic agents include: 5-(2,4-difluoro-phenoxy)-1-isobutyl-1H-indazole-6-carboxylic acid (2-dimethylamino-ethyl)-amide (P38 Map kinase inhibitor ARRY-797); 3-cyclopropylmethoxy-N-(3,5-dichloro-pyridin-4-yl)-4-difluoromethoxy-benzamide (PDE-4 inhibitor roflumilast); 4-[2-(3-cyclopentoxy-4-methoxyphenyl)-2-phenyl-ethyl]-pyridine (PDE-4 inhibitor) CDP-840); N-(3,5-dichloro-4-pyridinyl)-4-(difluoromethoxy)-8-[(methanesulfonyl)amino]-1-dibenzofuran carboxamide (PDE-4 inhibitor Omister); N-(3,5-dichloropyridin-4-yl)-2-[1-(4-fluorobenzyl)-5-hydroxy-1H-indol-3-yl]-2-oxo-acetamide (PDE-4 inhibitor AWD12-281); 8-methoxy-2-trifluoromethyl-quinoline-5-carboxylic acid (3,5-dichloro-1-oxy) 4-pyridin-4-yl)-amide (PDE-4 inhibitor Sch351591); 4-[5-(4-fluorophenyl)-2-(4-methylsulfinyl-phenyl)-1H-imidazol-4-yl]-pyridine (P38 inhibitor SB-203850); 4-[4-(4-fluorophenyl)-1-(3-phenyl-propyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-but-3-yn-1-ol (P38 inhibitor RWJ-67657); 4-cyano-4-(3-cyclopentoxy-4-methoxy) 2-Diethylamino-ethyl ester of (-phenyl)-cyclohexanecarboxylic acid (2-diethyl-ethyl ester prodrug of silostabdominal, PDE-4 inhibitor); (3-chloro-4-fluorophenyl)-[7-methoxy-6-(3-morpholin-4-yl-propoxy)-quinazolin-4-yl]-amine (gefitinib, EGFR inhibitor); and 4-(4-methyl-piperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-benzamide (imatinib, EGFR inhibitor).

[0083] In some embodiments, the unit dose of the pharmaceutical composition is 0.001 mg to 1000 mg.

[0084] In some embodiments, the pharmaceutical composition contains 0.01% to 99.99% of the aforementioned compound based on the total weight of the composition. In some embodiments, the pharmaceutical composition contains 0.1% to 99.9% of the aforementioned compound. In some embodiments, the pharmaceutical composition contains 0.5% to 99.5% of the aforementioned compound. In some embodiments, the pharmaceutical composition contains 1% to 99% of the aforementioned compound or its stereoisomers, solvates, prodrugs, stable isotope derivatives, or pharmaceutically acceptable salts thereof. In some embodiments, the pharmaceutical composition contains 2% to 98% of the aforementioned compound or its stereoisomers, solvates, prodrugs, stable isotope derivatives, or pharmaceutically acceptable salts thereof.

[0085] In some embodiments, the pharmaceutical composition contains 0.01% to 99.99% pharmaceutically acceptable carriers, diluents, or excipients based on the total weight of the composition. In some embodiments, the pharmaceutical composition contains 0.1% to 99.9% pharmaceutically acceptable carriers, diluents, or excipients. In some embodiments, the pharmaceutical composition contains 0.5% to 99.5% pharmaceutically acceptable carriers, diluents, or excipients. In some embodiments, the pharmaceutical composition contains 1% to 99% pharmaceutically acceptable carriers, diluents, or excipients. In some embodiments, the pharmaceutical composition contains 2% to 98% pharmaceutically acceptable carriers, diluents, or excipients.

[0086] All compounds involved in this invention, as well as mixtures and compositions comprising compounds of this invention, can be administered to a living organism via any route of administration. Routes of administration may include oral administration, intravenous injection, intramuscular injection, subcutaneous injection, rectal administration, vaginal administration, sublingual administration, nasal inhalation, oral inhalation, eye drops, or local or systemic transdermal administration.

[0087] All compounds involved in this invention, as well as mixtures and compositions containing compounds of this invention, can be formulated into single doses, containing the active compounds of this invention, as well as carriers, excipients, etc. The dosage forms can be tablets, capsules, injections, granules, powders, suppositories, pills, creams, pastes, gels, powders, oral solutions, inhalers, suspensions, dry suspensions, patches, lotions, etc. These dosage forms may contain commonly used pharmaceutical ingredients, such as diluents, absorbents, wetting agents, binders, disintegrants, colorants, pH adjusters, antioxidants, antibacterial agents, isotonic adjusters, anti-adhesives, etc.

[0088] Suitable formulations for the aforementioned dosage forms are available from publicly available sources, such as Remington: The Science and Practice of Pharmacy, 21st Edition, Lippincott Williams & Wilkins, 2006, and Rowe, Raymond C. Handbook of Pharmaceutical Excipients, Chicago, Pharmaceutical Press, 2005. Therefore, those skilled in the art can readily prepare them.

[0089] Depending on the nature and severity of the disease suffered by different individuals, as well as factors such as age, sex, weight, and route of administration, different dosages can be selected. The dosage of the compound of the present invention can be from 0.01 to 500 mg / kg per day, preferably 1-100 mg / kg per day, and can be administered once or multiple times.

[0090] Experiments have verified that the compounds of this invention or their salts have the following effects:

[0091] (a) The compound of Formula I described in this invention can efficiently inhibit the replication of paramyxoviridae viruses and has very little toxicity to normal cells;

[0092] (b) The compound of formula I described in this invention has high in vivo inhibitory activity against paramyxoviridae viruses;

[0093] (c) The compound of Formula I described in this invention exhibits low toxicity in animals, high oral bioavailability, stable metabolism, and good drug-like properties. This suggests that the active compound of this invention has excellent pharmaceutical prospects in the treatment of paramyxovirial infections.

[0094] Terminology Explanation:

[0095] Unless otherwise stated, the terms used in the specification and claims have the following meanings.

[0096] Term "C" 1-20"Alkyl" refers to a saturated aliphatic hydrocarbon group, which is a straight-chain or branched group containing 1 to 20 carbon atoms, preferably an alkyl group containing 1 to 12 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12) carbon atoms, more preferably an alkyl group containing 1 to 6 carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, and 1,1-dimethylbutyl. 1,2-Dimethylbutyl, 2,2-Dimethylbutyl, 1,3-Dimethylbutyl, 2-Ethylbutyl, 2-Methylpentyl, 3-Methylpentyl, 4-Methylpentyl, 2,3-Dimethylbutyl, n-Heptyl, 2-Methylhexyl, 3-Methylhexyl, 4-Methylhexyl, 5-Methylhexyl, 2,3-Dimethylpentyl, 2,4-Dimethylpentyl, 2,2-Dimethylpentyl, 3,3-Dimethylpentyl, 2-Ethylpentyl, 3-Ethylpentyl, n-Octyl, 2,3-Dimethylhexyl, 2,4-Dimethylhexyl, 2,5-Dimethylhexyl, 2,2-Dimethylhexyl, 3,3-Dimethylhexyl, 4,4-Dimethylhexyl, 2-Ethylhexyl, 3- Ethylhexyl, 4-ethylhexyl, 2-methyl-2-ethylpentyl, 2-methyl-3-ethylpentyl, n-nonyl, 2-methyl-2-ethylhexyl, 2-methyl-3-ethylhexyl, 2,2-diethylpentyl, n-decyl, 3,3-diethylhexyl, 2,2-diethylhexyl, and their various branched isomers, etc. More preferably, lower alkyl groups containing 1 to 6 carbon atoms, and non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1 -Ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, etc. The alkyl group may be substituted or unsubstituted, and when substituted, it may be substituted at any usable connection point. The substituent is preferably independently selected independently from one or more substituents chosen from the group consisting of a D atom, halogen, alkoxy, haloalkyl, haloalkoxy, cycloalkyloxy, heterocyclic oxy, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclic, aryl, and heteroaryl.

[0097] Term "C" 1-20 "alkylyl" means that the group C 1-20 Alkyl-C(O)-, where "C1-20 "alkyl" means as defined above.

[0098] Term "C" 3-10 "Cycloalkyl" refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon substituent, wherein the cycloalkyl ring contains 3 to 10 carbon atoms, preferably 3 to 8 (e.g., 3, 4, 5, 6, 7, and 8) carbon atoms, and more preferably 3 to 6 carbon atoms. Non-limiting examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cyclohepttrienyl, cyclooctyl, etc.; polycyclic cycloalkyl groups include spirocyclic, fused-ring, and bridged-ring cycloalkyl groups.

[0099] The cycloalkyl group can be substituted or unsubstituted, and when substituted, it can be substituted at any usable connection point. The substituent is preferably selected independently from one or more substituents selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, cycloalkyloxy, heterocyclic oxy, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclic, aryl and heteroaryl.

[0100] Term "C" 3-10 "Cycloalkylformyl" means that the group C 3-10 cycloalkyl-C(O)-, where "C 3-10 "Cycloalkyl" means as defined above.

[0101] The term "halogen" refers to fluorine, chlorine, bromine, or iodine.

[0102] The term "hydroxyl group" refers to -OH.

[0103] The term "amino" refers to -NH2.

[0104] The term "cyano" refers to -CN.

[0105] The term "substituted" refers to one or more hydrogen atoms in a group, preferably up to five, more preferably one to three hydrogen atoms, that are independently substituted by the corresponding number of substituents. It goes without saying that the substituents are only in their possible chemical positions, and those skilled in the art can determine (by experiment or theory) possible or impossible substitutions without much effort. For example, an amino or hydroxyl group with free hydrogen may be unstable when combined with a carbon atom having an unsaturated bond (such as an alkene).

[0106] In the chemical structure of the compound described in this invention, the bond... No configuration was specified, i.e., key It can be Or simultaneously include Two configurations.

[0107] The term "stereoisomer" refers to compounds that have the same chemical structure but different spatial arrangements of atoms or groups. Stereoisomers include enantiomers, diastereomers, conformational isomers (rotational isomers), geometric (cis / trans) isomers, and hindered isomers, etc.

[0108] The term "isotope derivative" refers to compounds whose structure differs only in the presence of one or more isotope-enriched atoms. For example, compounds with the structure of this invention use "deuterium" or "tritium" instead of hydrogen, or use... 18 F-fluorine labeling ( 18 F isotopes) can be used instead of fluorine, or... 11 C-, 13 C-, or 14 C-enriched carbon ( 11 C-, 13 C-, or 14 C-carbon labeling; 11 C-, 13 C-, or 14 Compounds in which carbon atoms are replaced by C-isotopes are within the scope of this invention. Such compounds can be used as analytical tools or probes in biological assays, or as in vivo diagnostic imaging tracers for diseases, or as tracers for pharmacodynamic, pharmacokinetic, or receptor studies. The various deuterated forms of compounds in this invention refer to compounds in which each available hydrogen atom bonded to a carbon atom can be independently replaced by a deuterium atom. Those skilled in the art can synthesize deuterated forms of compounds by referring to relevant literature. Commercially available deuteration starting materials can be used in the preparation of deuterated forms of compounds, or they can be synthesized using conventional techniques with deuteration reagents, including but not limited to deuterated boranes, trideuterated borane tetrahydrofuran solutions, deuterated lithium aluminum hydride, deuterated iodoethane, and deuterated iodomethane. Deuterated compounds generally retain activity comparable to undeuterated compounds, and better metabolic stability can be achieved when deuterated at certain specific sites, thus providing certain therapeutic advantages.

[0109] The term "pharmaceutically acceptable salt" means that the compounds of the present invention exist in the form of their pharmaceutical salts, including acid addition salts and base addition salts. Pharmaceutically acceptable salts are described in SMBerge's description of pharmaceutically acceptable salts in J. Pharmaceutical Sciences (Vol. 66: 1-19, 1977). In the present invention, a pharmaceutically acceptable non-toxic acid addition salt means a salt formed by the compounds of the present invention with an organic or inorganic acid, including but not limited to hydrochloric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, nitric acid, perchloric acid, acetic acid, oxalic acid, maleic acid, fumaric acid, tartaric acid, benzenesulfonic acid, methanesulfonic acid, salicylic acid, succinic acid, citric acid, lactic acid, propionic acid, benzoic acid, p-toluenesulfonic acid, malic acid, etc. Pharmaceutically acceptable non-toxic base addition salts refer to salts formed by the compounds of this invention with organic or inorganic bases, including but not limited to alkali metal salts, such as lithium, sodium, or potassium salts; alkaline earth metal salts, such as calcium or magnesium salts; and organic base salts, such as ammonium salts or N-containing organic bases. + (C 1-6 Alkyl)4 salt.

[0110] The term "solvent" refers to the physical bond between the compound of the present invention and one or more, preferably one to three, solvent molecules, whether organic or inorganic. This physical bond includes hydrogen bonds. In some cases, for example, when one or more, preferably one to three, solvent molecules are incorporated into the lattice of a crystalline solid, the solvate will be separated. Exemplary solvates include, but are not limited to, hydrates, ethanolates, methanolates, and isopropanolates. Solvation methods are well known in the art.

[0111] The term "prodrug" refers to a compound that can be converted in the body to produce an active drug substance under physiological conditions, such as through hydrolysis in the blood.

[0112] The term "pharmaceutical composition" refers to a mixture containing one or more of the compounds described herein or their physiologically / pharmacologically acceptable salts or prodrugs, along with other chemical components, such as physiologically / pharmacologically acceptable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration to a living organism, thereby promoting the absorption of the active ingredient and the exertion of its biological activity.

[0113] The terms involved in this invention have been defined above. Those skilled in the art can also understand the above terms in conjunction with the prior art. The following is a further description based on the content of this invention and the definition of the terms.

[0114] The following examples further illustrate the preparation of the compounds and pharmaceutically acceptable salts of the present invention, but these examples are not intended to limit the scope of the present invention. The compounds involved in the present invention can be prepared in a similar manner.

[0115] Experimental methods in the embodiments of this invention that do not specify specific conditions are generally performed under conventional conditions or as recommended by the raw material or product manufacturer. Reagents whose specific source is not specified are commercially available conventional reagents.

[0116] Example 1: Preparation of Compound 6

[0117] Compound 6 of the present invention was prepared by the synthetic method of compound A50 described in Preparation Example 12 of the specification in WO2021213288A1 (which is incorporated herein by reference).

[0118] Example 2: Preparation of Compound 25

[0119] Compound 25 of the present invention was prepared by the synthetic method of compound 25 described in Example 2 of the specification CN117298120A (which is incorporated herein by reference).

[0120] Example 3: Preparation of Compound 27

[0121] Compound 27 of the present invention was prepared by the synthetic method of compound A131 described in Preparation Example 35 of the specification in WO2021213288A1.

[0122] Example 4: Preparation of compound 42

[0123] Compound 42 of the present invention was prepared by the synthetic method of compound A151 described in Preparation Example 36 of the specification in WO2021213288A1. The hydrobromide of compound 42 was prepared by the preparation method described in paragraph 0096 of Example 1 of the specification in CN114391016A (which is incorporated herein by reference).

[0124] Example 5: Preparation of Compound 4

[0125] Compound 4 of the present invention was prepared by the synthetic method of compound A9 described in Preparation Example 5 of the specification WO2021213288A1.

[0126] Example 6: Preparation of Compound 11

[0127] Compound 11 of the present invention was prepared by the synthetic method of compound A70 described in Preparation Example 17 of the specification WO2021213288A1.

[0128] Example 7: Preparation of Compound 20

[0129] Compound 20 of the present invention was prepared by the synthetic method of compound A124 described in Preparation Example 11 of the specification WO2021213288A1.

[0130] Example 8: Preparation of compound 29

[0131] Compound 29 of the present invention was prepared by the synthetic method of compound A138 described in Preparation Example 41 of the specification in WO2021213288A1.

[0132] Example 9: Preparation of Compound 40

[0133] Compound 40 of the present invention was prepared by the synthetic method of compound 40 described in Example 9 of the specification in CN117298120A.

[0134] Example 10: Preparation of Compound 52

[0135] Compound 52 of the present invention was prepared by the synthetic method of compound 52 described in Example 10 of the specification in CN117298120A.

[0136] Example 11: Preparation of Compound 32

[0137] Compound 32 of the present invention was prepared by the synthetic method of compound 32 described in Example 11 of the specification in CN117298120A.

[0138] Example 12: Preparation of Compound 53

[0139] Compound 53 of the present invention was prepared by the synthetic method of compound 53 described in Example 12 of the specification in CN117298120AA.

[0140] Experimental Example

[0141] Experimental Example 1: Determination of the inhibitory activity of the compound of the present invention against human metapneumovirus:

[0142] Healthy LLC-MK2 cells (ATCC(CCL-7)) were seeded into 96-well plates. When the cells reached 80%-90% confluence, 0.1 MOI of human metapneumovirus (HMPV) and 1, 5, or 100 μM of the test compound were added to each well. Cell controls and virus controls were also included. All wells contained 1% DMSO. After incubation at 37°C for 48 h, the cell supernatant was collected. The inhibitory activity of the compound against the virus was assessed by quantitative real-time RT-PCR (qRT-PCR) to quantify the viral copy number in the cell supernatant.

[0143] Table 1. In vitro inhibitory activity of the compounds of the present invention against human metapneumovirus (HMPV).

[0144] As can be seen from Table 1, the compounds of the present invention can inhibit the replication of human metapneumovirus (HMPV) in vitro.

[0145] Experimental Example 2: Determination of the inhibitory activity of the compound of the present invention against human parainfluenza virus:

[0146] LLC-MK2 cells (ATCC(CCL-7)) in good growth condition were seeded in 96-well plates. When the cells reached 80%-90% confluence, 0.1 MOI of human parainfluenza type 3 virus (HPIV-3) (ATCC(VR-93)) and different concentrations (single-concentration inhibition rates are shown in the table, EC50 concentration gradients are 10, 3.33, 1.11, 0.37, 0.123, 0.041) of the test compound were added to each well. Cell controls and virus controls were also set up. All wells contained 1% DMSO. Cells were cultured in an incubator at 5% CO2, 33°C or 37°C for 2 or 5 days until cells in the virus-infected control wells without the compound showed obvious lesions. Then, the cells were treated with CellTiter-Glo luminescence assay reagent (Promega, Madison, WI, USA), and the half-maximal effective concentration (EC50) of the compound against the virus was calculated using GraphPad Prism 7 software. 50 )value.

[0147] Table 2. In vitro inhibitory activity of the compounds of the present invention against human parainfluenza virus type 3 (HPIV-3).

[0148] As can be seen from Table 2, the compounds of the present invention can inhibit the replication of human parainfluenza virus type 3 (HPIV-3) in vitro.

[0149] Experimental Example 3: Determination of the inhibitory activity of the compound of the present invention against canine distemper virus:

[0150] Take Vero cells in good growth condition and seed them into 96-well plates. When the cells reach 80%-90% confluence, add 0.1 MOI of canine distemper virus and different concentrations (single concentration inhibition rates are shown in the table, EC50) to each well. 50 Test compounds were prepared at concentration gradients of 10, 3.33, 1.11, 0.37, 0.123, and 0.041, with cell and virus controls included. All wells contained 1% DMSO. After incubation at 37°C for 72 hours, cell supernatants were collected, and the inhibitory activity of the compounds against the virus was assessed by quantitative real-time RT-PCR (qRT-PCR) to quantify the viral copy number in the cell supernatant.

[0151] Table 3. In vitro inhibitory activity of the compounds of the present invention against canine distemper virus.

[0152] As can be seen from Table 3, the compounds of the present invention can replicate canine distemper virus in vitro.

Claims

1. The use of a compound of Formula I or a stereoisomer thereof, solvate, prodrug, stable isotopic derivative thereof, or a pharmaceutically acceptable salt thereof in the preparation of an inhibitor of the replication of paramyxoviridae viruses. in, R1 is selected from hydrogen, substituted or unsubstituted C. 1-20 Alkyl group, substituted or unsubstituted C 3-10 Cycloalkylformyl group, wherein the substitution is performed by one or more Q1 groups; R2 is selected from hydrogen, substituted or unsubstituted C. 1-20 Alkyl group, substituted or unsubstituted C 3-10 Cycloalkylformyl group, wherein the substitution is performed by one or more Q2 groups; Or formed by connecting R1 and R2 together. R3 is selected from hydrogen, substituted or unsubstituted C. 1-20 Alkyl group, substituted or unsubstituted C 3-10 Cycloalkylformyl group, wherein the substitution is performed by one or more Q3 groups; Q1, Q2, and Q3 are each independently selected from cyano, amino, hydroxyl, and halogen groups; R4 is selected from hydrogen, deuterium, cyano, amino, hydroxyl, and halogen.

2. The application according to claim 1, characterized in that, In Formula I, R1 is selected from hydrogen, and Q1 is substituted or unsubstituted C. 1-18 Alkyl group, Q1 substituted or unsubstituted C 3-7 Cycloalkylformyl; preferably hydrogen, Q1 substituted or unsubstituted C 1-18 Alkyl group, Q1 substituted or unsubstituted C 3-6 Cycloalkylformyl; wherein, Q1 is selected from amino, hydroxyl, and halogen, preferably amino and halogen, most preferably amino; R1 is more preferably hydrogen, formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, 2-aminoisovaleryl, pterovaleryl, hexanoyl, 2-ethylbutyryl, 3,3-dimethylbutyryl, heptanoyl, octanoyl, 2-propylvaleryl, nonanoyl, decanoyl, C 13 Alkyl group, C 14 Alkyl group, C 15 Alkyl group, C 16 Alkyl group, C 17 Alkyl group, C 18 Alkyl, cyclopropylformyl, cyclobutylformyl, cyclopentylformyl, and cyclohexylformyl, particularly selected from hydrogen, acetyl, propionyl, isobutyryl, 2-aminoisovaleryl, pivaloyl, 2-ethylbutyryl, 3,3-dimethylbutyryl, 2-propylvaleryl, C 13 Alkyl group, C 15 Alkyl group, C 17 Alkyl group; and / or In Formula I, R2 is selected from hydrogen, Q2-substituted or unsubstituted C. 1-18 Alkyl group, Q2 substituted or unsubstituted C 3-7 Cycloalkylformyl; preferably hydrogen, Q2 substituted or unsubstituted C 1-18 Alkyl group, Q2 substituted or unsubstituted C 3-6 Cycloalkylformyl; Q2 is selected from amino, hydroxyl, and halogen, preferably amino and halogen, most preferably hydrogen and amino; R2 is more preferably hydrogen, formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, 2-aminoisovaleryl, pterovaleryl, hexanoyl, 2-ethylbutyryl, 3,3-dimethylbutyryl, heptanoyl, octanoyl, 2-propylvaleryl, nonanoyl, decanoyl, C 13 Alkyl group, C 14 Alkyl group, C 15 Alkyl group, C 16 Alkyl group, C 17 Alkyl group, C 18 Alkyl, cyclopropylformyl, cyclobutylformyl, cyclopentylformyl, and cyclohexylformyl, particularly selected from hydrogen, acetyl, propionyl, isobutyryl, 2-aminoisovaleryl, pivaloyl, 2-ethylbutyryl, 3,3-dimethylbutyryl, 2-propylvaleryl, C 13 Alkyl group, C 15 Alkyl group, C 17 Alkyl group; and / or In Formula I, R3 is selected from hydrogen, Q3-substituted or unsubstituted C. 1-18 Alkyl group, Q3 substituted or unsubstituted C 3-7 Cycloalkylformyl; preferably hydrogen, Q3 substituted or unsubstituted C 1-18 Alkyl group, Q3 substituted or unsubstituted C 3-6 Cycloalkylformyl; Q3 is selected from amino, hydroxyl, and halogen, preferably amino and halogen, most preferably hydrogen and amino; R3 is more preferably hydrogen, formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, 2-aminoisovaleryl, pterovaleryl, hexanoyl, 2-ethylbutyryl, 3,3-dimethylbutyryl, heptanoyl, octanoyl, 2-propylvaleryl, nonanoyl, decanoyl, C 13 Alkyl group, C 14 Alkyl group, C 15 Alkyl group, C 16 Alkyl group, C 17 Alkyl group, C 18 Alkyl, cyclopropylformyl, cyclobutylformyl, cyclopentylformyl, and cyclohexylformyl, particularly selected from hydrogen, acetyl, propionyl, isobutyryl, 2-aminoisovaleryl, pivaloyl, 2-ethylbutyryl, 3,3-dimethylbutyryl, 2-propylvaleryl, C 13 Alkyl group, C 15 Alkyl group, C 17 Alkyl group; and / or In Formula I, R4 is selected from hydrogen, deuterium, and halogens, preferably hydrogen, deuterium, fluorine, chlorine, and iodine.

3. The application according to claim 1 or 2, characterized in that, In Formula I, R1 and R2 are not both hydrogen.

4. The application according to claim 1, characterized in that, In Formula I, R1, R2, and R3 are each independently selected from hydrogen, acetyl, propionyl, isobutyryl, and 2-ethylbutyryl. Alternatively, R1 and R2 can be connected to form a... R4 is selected from hydrogen and deuterium.

5. The application according to claim 1, characterized in that, The compound represented by Formula I is selected from any of the following:

6. The use of a compound of Formula I as described in any one of claims 1-5, or a stereoisomer thereof, solvate, prodrug, stable isotope derivative thereof, or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for treating and / or preventing or alleviating diseases related to infection by paramyxoviridae viruses.

7. The use of a composition comprising a compound of Formula I as described in any one of claims 1-5, or a stereoisomer thereof, a solvate, a prodrug, a stable isotopic derivative thereof, or a pharmaceutically acceptable salt thereof, in the preparation of an inhibitor for inhibiting the replication of paramyxoviridae viruses.

8. The use of a composition comprising a compound of Formula I as described in any one of claims 1-5, or a stereoisomer thereof, a solvate, a prodrug, a stable isotopic derivative thereof, or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for treating and / or preventing or alleviating diseases related to infection by paramyxoviridae viruses.

9. The application according to any one of claims 1-8, characterized in that, The paramyxoviridae viruses are selected from metapneumovirus, parainfluenza virus, measles virus, mumps virus, Nipah virus, Hendra virus, Newcastle disease virus, peste des petits ruminants virus, canine distemper virus, and duck plague virus; particularly, the paramyxoviridae viruses are selected from metapneumovirus, parainfluenza virus, canine distemper virus, measles virus, mumps virus, Nipah virus, and Hendra virus; more particularly, the paramyxoviridae viruses are selected from metapneumovirus, parainfluenza virus, and canine distemper virus.

10. The application according to claim 6 or 8, characterized in that, The diseases caused by paramyxoviridae virus infections are selected from the following group: (1) Common cold, high-risk symptom infection, respiratory tract infection, bronchitis, pneumonia and its complications caused by metapneumovirus infection; (2) Common cold, high-risk symptom infection, respiratory tract infection, bronchitis, pneumonia and their complications caused by parainfluenza virus infection; (3) Measles, common cold, high-risk symptom infection, respiratory infection, bronchitis, pneumonia and their complications caused by measles virus infection; (4) High-risk symptoms of mumps virus infection, including mumps, orchitis, meningitis, bronchitis, pneumonia and its complications; (5) High-risk symptoms of Nipah virus infection, including respiratory infections, encephalitis, pneumonia and its complications; (6) High-risk symptomatic infections, encephalitis, pneumonia and their complications caused by Hendra virus infection; (7) Newcastle disease caused by Newcastle disease virus infection and its complications; (8) Peste des petits ruminants (PPR) virus infection and its complications; (9) Canine distemper caused by canine distemper virus infection and its complications; (10) Duck plague virus infection causes duck plague and its complications; (11) Any combination of the above diseases; Specifically, the diseases caused by paramyxoviridae virus infections are selected from the following group: (1) Common cold, high-risk symptom infection, respiratory tract infection, bronchitis, pneumonia and its complications caused by metapneumovirus infection; (2) Common cold, high-risk symptom infection, respiratory tract infection, bronchitis, pneumonia and their complications caused by parainfluenza virus infection; (3) Measles, common cold, high-risk symptom infection, respiratory infection, bronchitis, pneumonia and their complications caused by measles virus infection; (4) High-risk symptoms of mumps virus infection, including mumps, orchitis, meningitis, bronchitis, pneumonia and its complications; (5) High-risk symptoms of Nipah virus infection, including respiratory infections, encephalitis, pneumonia and its complications; (6) High-risk symptomatic infections, encephalitis, pneumonia and their complications caused by Hendra virus infection; (7) Canine distemper caused by canine distemper virus infection and its complications; (8) Any combination of the above diseases; More specifically, the diseases caused by paramyxoviridae virus infections are selected from the following group: (1) Common cold, high-risk symptom infection, respiratory tract infection, bronchitis, pneumonia and its complications caused by metapneumovirus infection; (2) Common cold, high-risk symptom infection, respiratory tract infection, bronchitis, pneumonia and their complications caused by parainfluenza virus infection; (3) Canine distemper caused by canine distemper virus infection and its complications; (4) Any combination of the above diseases.

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