Phenyl-N-quinoline derivatives for treating RNA virus infections

Abstract

To provide compounds suitable for the prevention and / or treatment of a RNA virus infection caused by RNA viruses belonging to group IV or V of the Baltimore classification.SOLUTION: The present invention provides a compound of the formula (I), or its pharmaceutically acceptable salts. Specifically, for example, 8-chloro-N-(2-methyl-4-(trifluoromethoxy)phenyl)quinolin-2-amine is illustrated.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to compounds useful for preventing and / or treating RNA viral infections, most preferably those caused by RNA viruses belonging to Group IV or Group V of the Baltimore Classification.

[0002] The present invention further relates to certain novel compounds, in particular certain novel compounds useful for preventing and / or treating RNA viral infections, most preferably RNA viral infections caused by RNA viruses belonging to Group IV or Group V of the Baltimore Classification.

[0003] The present invention further relates to pharmaceutical compositions containing the above-mentioned novel compounds, and to chemical synthesis methods for obtaining them. [Background technology]

[0004] Viruses are one of the major causes of disease worldwide. Viruses are generally defined as small, non-living infectious agents that replicate only inside living cells, as they lack a fully autonomous replication mechanism. Although they vary in shape and size, viruses typically consist of a virus particle (known as a "virion") made up of at least one nucleic acid molecule and, optionally, a protein coat containing one or more proteins or nucleoproteins, depending on the type of virus.

[0005] Viruses do not possess a completely autonomous replication mechanism and therefore must necessarily depend on the machinery and metabolism of the infected cell or host to replicate and produce multiple copies of themselves.

[0006] Although viral replication cycles vary widely among species, it is generally accepted that the viral life cycle involves six basic steps: attachment, entry, uncoating, replication, assembly, and release.

[0007] Depending on the nature of the target virus, therapeutic molecules have been designed that can interfere with one or more of these mechanisms.

[0008] Among them, the replication process also includes the multiplication of the viral genome, as well as the synthesis of viral messenger RNA for viral protein synthesis, and the regulation or use of the host's transcription or translation machinery. However, it is also clear that the type of genome (single-stranded, double-stranded, RNA, DNA, etc.) dramatically characterizes this replication process. For example, most DNA viruses assemble in the nucleus, whereas most RNA viruses unfold exclusively in the cytoplasm. There is also growing evidence that single-stranded RNA viruses, such as influenza, use the host's RNA splicing and maturation machinery.

[0009] Therefore, taking into account the influence of a given type of genome on the replication process, the Baltimore classification of viruses was developed. This classification clusters viruses into families (or "groups") depending on the viral type of the genome. As of 2018, the current virus classification consists of seven different groups: Group I: double-stranded DNA viruses (dsDNA); Group II: single-stranded DNA viruses (ssDNA); Group III: double-stranded RNA viruses (dsRNA); Group IV: (+) strand or sense viruses ((+)ssRNA); Group V: (-)strand or antisense RNA viruses ((-)ssRNA); Group VI: single-stranded RNA viruses with DNA intermediates (ssRNA-RT); Group VII: double-stranded DNA viruses with an RNA intermediate (dsDNA-RT).

[0010] According to that classification, viruses belonging to group VI are not RNA viruses in the strict sense. For the same reason, viruses belonging to group VII are not DNA viruses in the strict sense. One well-studied example of a virus family belonging to group VI is the Retroviridae (retroviruses), which includes HIV. One well-studied example of a virus family belonging to group VII is the Hepadnaviridae, which includes the Hepatitis B virus (HBV).

[0011] Representatives of viruses related to group IV may include Picornaviruses (a virus family that includes well-known viruses such as Hepatitis A virus, enteroviruses, rhinoviruses, poliovirus, and foot-and-mouth virus), SARS virus, Hepatitis C virus, yellow fever virus, and rubella virus. The Togaviridae family also belongs to group IV, and its known genus is the alphavirus, which includes the Chikungunya virus. The Flaviridae family also belongs to group IV, and includes the well-known mosquito-borne virus, namely the Dengue virus.

[0012] Representatives of viruses related to group V may include the Filoviridae virus family, which includes the Ebola virus, the Paramyxoviridae family, which includes the Respiratory Syncytial virus (RSV), the Rhabdoviridae family, and the Orthomyxoviridae family, which includes influenza A virus, influenza B virus, and influenza C virus.

[0013] A group within the virus family that is particularly focused on within the framework of the present invention is the viruses that include the RNA viruses, in particular the single-stranded RNA viruses, and more particularly the RNA viruses that belong to Group IV or Group V of the Baltimore Classification.

[0014] There are few treatments for diseases caused by RNA virus infections, especially single-stranded RNA viruses, more especially RNA virus infections from viruses belonging to groups IV and V of the Baltimore classification. Treatments are focused on alleviating symptoms. Therefore, RNA virus infections, such as RNA virus infections from groups IV and V, are difficult to treat. of There remains a need to identify new antiviral agents, especially small chemical molecules, for treatment. Summary of the Invention

[0015] definition

[0016] As used herein, the term "patient" refers to either an animal, such as a valuable animal for purposes of breeding, company or conservation, or, preferably, a human or human child who is suffering from or may be suffering from one or more of the diseases and conditions described herein.

[0017] In particular, as used in this application, the term "patient" refers to a mammal, such as a rodent, cat, dog, primate or human, preferably the subject is a human, and also extends to birds.

[0018] Identifying patients in need of treatment for the diseases and conditions described herein is well within the ability and knowledge of one of ordinary skill in the art, and a veterinarian or physician skilled in the art can readily identify patients in need of such treatment by using clinical tests, physical examinations, medical / family history, or biological and diagnostic tests.

[0019] In the context of the present invention, the term "treat" or "treatment" as used herein means to reverse, alleviate, inhibit the progression of a disease caused by an RNA virus infection, more particularly an RNA virus infection from group IV or V, or one or more symptoms of such a disease, or to prevent said disease or symptoms.

[0020] As used herein, "effective amount" refers to an amount of a compound of the present invention that is effective in preventing, alleviating, eliminating, treating, or controlling the symptoms of the diseases and conditions described herein, i.e., RNA viral infections, more particularly RNA viral infections from Groups IV and V. The term "control" is intended to refer to any process that may slow, interrupt, hinder, or stop the progression of the diseases and conditions described herein, but does not necessarily indicate the complete elimination of the symptoms of all diseases and conditions, and is intended to encompass prophylactic treatment.

[0021] The term "effective amount" encompasses a "prophylactically effective amount" as well as a "therapeutically effective amount."

[0022] As used herein, the term "prevent" means reducing the risk or delaying the onset of a given phenomenon, i.e., a disease caused by an RNA viral infection, more particularly an RNA viral infection from group IV or V, in this invention.

[0023] As used herein, "prevent" also encompasses "reducing the likelihood of onset" or "reducing the likelihood of re-onset."

[0024] The term "prophylactically effective amount" refers to a concentration of a compound of the present invention that is effective in preventing delayed onset of disease due to an RNA virus, more particularly an RNA virus from Group IV or Group V, in inhibiting, preventing, reducing the likelihood of disease due to an RNA virus, more particularly an RNA virus from Group IV and Group V of the Baltimore classification, or in preventing an RNA virus infection, more particularly an RNA virus infection from Group IV and Group V, when administered prior to infection, i.e., before, during and / or shortly after the period of exposure to an RNA virus, more particularly an RNA virus from Group IV or Group V.

[0025] Similarly, the term "therapeutically effective amount" refers to a concentration of a compound that is effective in treating an RNA virus infection, e.g., a concentration of a compound that, when administered after infection has occurred, results in a reduction in an RNA virus infection after testing.

[0026] As used herein, the term "pharmacologically acceptable" refers to a compound, substance, excipient, composition, or dosage form that is, within the scope of sound medical judgment, suitable for contact with the tissues of human beings and animals without undue toxicity, irritation, allergic response, or other problem complications commensurate with a reasonable benefit / risk ratio.

[0027] As used herein, "viral infection or virus-associated condition" refers to infection with a virus, more particularly a condition associated with a virus having an RNA genome, especially an RNA virus belonging to Group IV or Group V according to the Baltimore classification. Viruses can be further classified into different families, orders and genera.

[0028] For reference, the contents of the "Baltimore Classification" reported in this specification further refer to the virus classification set out in the 2017 International Committee of Taxonomy of Viruses (ICTV) database, released online on March 12, 2018, at http: / / ictvonline.org / virusTaxonomy.asp, which is incorporated herein in its entirety.

[0029] Alphaviruses may in particular be considered by the present invention and may be related to group IV RNA viruses and the Togaviridae family, which may be defined as positive-sense single-stranded RNA viruses or (+)ssRNA viruses. According to the 2017 virus classification, their order is "unassigned". The Togaviridae family includes the genera Alphavirus and Rubivirus.

[0030] Examples of alphaviruses contemplated by the present invention include: Barmah Forest virus, Chikungunya virus, Mayaro virus, O'nyong'nyong virus, Ross River virus, Semliki Forest virus, Una virus, Eastern equine encephalitis virus, Tonate virus, Venezuelan equine encephalitis virus, and Western equine encephalitis virus.

[0031] More preferably, the alpha-virus infection or alpha-virus associated state according to the present invention is a chikungunya virus infection or a chikungunya virus associated state.

[0032] More specifically, Chikungunya virus (CHIKV) is an RNA virus belonging to the genus Alphavirus, which belongs to the family Togaviridae, i.e., group IV of the Baltimore classification. Chikungunya fever is a mosquito-borne viral disease that was first reported in 1952 during an outbreak in southern Tanzania. CHIKV is an enveloped, positive-sense, single-stranded RNA virus with a genome of approximately 12 kb nucleotides in length. The genome of CHIKV is organized as follows: 5'-cap-nsPl-nsP2-nsP3-nsP4-(junction region)-C-E3-E2-6k-El-poly(A)-3', in which the first four proteins (nsPl-4) are nonstructural proteins, and the structural proteins are capsid (C) and envelope proteins (E). There are no clear serotype differences between CHIKV isolated from Africa, Asia, and islands in the Indian Ocean. Phylogenetic analysis based on El gene sequences allowed grouping of CHIKV into three genotypes (lineages): Asian, east / central / south African (ECSA), and West African. The Asian genotypes differed from the ECSA and West African genotypes by -5% and -15%, respectively, at the nucleotide level. The African genotypes (ECSA vs. West Africa) diverged by -15%. Amino acid identity across the three genotypes varied from 95.2 to 99.8%.

[0033] Chikungunya virus can cause outbreaks associated with severe morbidity.

[0034] Chikungunya is a viral disease transmitted to humans by infected mosquitoes. Both Aedes aegypti (Ae. Aegypti) and Aedes albopictus (Ae. Albopictus) have been implicated in chikungunya outbreaks. Aedes aegypti is confined to the tropics and subtropics, while Aedes also occurs in temperate and cool temperate regions. In recent decades, Aedes albopictus has spread from Asia and established itself in areas of Africa, Europe, and the Americas.

[0035] After infection with the Chikungunya virus, there is an average incubation period of 2-4 days, followed by symptoms of the disease. Such symptoms may include fever and severe joint pain. Other symptoms include muscle pain, headache, nausea, back pain, fatigue, muscle pain, and rash. Severe clinical symptoms of Chikungunya fever may also occur, such as hemorrhagic fever, conjunctivitis, photophobia, hepatitis, and stomatitis. Neurological symptoms such as encephalitis, febrile convulsions, meningeal syndrome, and acute encephalopathy have also been reported.

[0036] Joint pain is often debilitating and can vary in duration.

[0037] The proximity of mosquito breeding sites to human habitation is a significant risk factor for chikungunya.

[0038] The distribution of the Chikungunya virus occurs mainly in Africa, India and Southeast Asia. In recent decades, the mosquito vector of Chikungunya has spread to Europe and the Americas. In 2007, disease transmission was first reported in a localized outbreak in northeastern Italy. Since then, outbreaks have been recorded in France and Croatia.

[0039] Dengue viruses, which exhibit various serotypes, may also be considered according to the present invention and are related to the group IV RNA viruses and the family Flaviviridae, which can be defined as positive-sense single-stranded RNA or (+)ssRNA viruses. More specifically, dengue virus is a (+)ssRNA virus belonging to group IV of the Baltimore classification. It is part of the genus Flavivirus, which belongs to the family Flaviviridae. Other viruses related to the family Flaviviridae are hepatitis C virus and yellow fever virus.

[0040] Viruses of the order Mononegavirales are also specifically contemplated by the present invention. The order Mononegavirales includes viruses belonging to group V of the Baltimore classification. As of 2018, this order mainly includes the following virus families: Bornaviridae, Mymonaviridae, Filoviridae, Nyamiviridae, Paramyxoviridae, Pneumoviridae, Rhabdoviridae, and Sunviridae.

[0041] Human respiratory syncytial virus (HRSV) is a syncytial virus that causes respiratory tract infections. It is a major cause of lower respiratory tract infections and hospital visits in infancy and childhood. HRSV virus may be considered in particular by the present invention and is related to group V of RNA viruses. More particularly, RSV virus is a (-)ssRNA virus belonging to group V of the Baltimore classification. It is a pneumovirus that is part of the family Paramyxoviridae, belonging to the order Mononegavirales. Among other viruses of the order Mononegavirales, those that are particularly considered by the present invention include measles virus, mumps virus, Nipah virus, rabies virus, and human parainfluenza virus (including HPIV-1, HPIV-2, HPIV-3, and HPIV). Of note, the subfamily of Paramyxoviridae has traditionally been integrated into the Paramyxoviridae family by reference to the 2016 updated classification of the Mononegavirales.

[0042] Virus genera of particular interest within the Paramyxoviridae family include the genera Aquaparamyxovirus, Avulavirus, Ferravirus, Henipavirus, Morbillivirus, Respirovirus, and Rubulavirus.

[0043] Viruses of the family Orthomyxoviridae are also specifically contemplated by the present invention. The family Orthomyxoviridae belongs to the order "Unassigned" according to the 2017 classification of viruses. Particularly contemplated virus genera in the family Orthomyxoviridae include Alphainfluenzavirus, Betainfluenzavirus, Deltainfluenzavirus, Gammainfluenzavirus, Isavirus, Quaranjavirus, and Thogotovirus.

[0044] Influenza virus A, influenza virus B, influenza virus C are particularly considered by the present invention and may relate to the group V RNA viruses and the family Orthomyxoviridae, which may be defined as negative-sense single-stranded RNA or (-)ssRNA viruses. Isavirus and Thogotovirus also belong to the order Orthomyxovirales. [Problem to be solved by the invention]

[0045] The present inventors have surprisingly discovered that phenyl-N-quinoline compounds have broad spectrum activity against RNA viruses, more particularly single-stranded RNA viruses belonging to Group IV or Group V of the Baltimore Classification, which respectively include (+)ssRNA viruses and (-)ssRNA viruses, which also refer to positive-sense single-stranded RNA viruses and negative-sense single-stranded RNA viruses.

[0046] For reference, the contents of the "Baltimore Classification" have been taken into account in the context of the classification and nomenclature of viruses as described in the 10th Report on Virus Taxonomy, 2017. [Means for solving the problem]

[0047] The present specification discloses a compound of the following formula (I), or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prophylaxis of an RNA virus infection caused by an RNA virus belonging to group IV or V of the Baltimore classification, in particular a chikungunya virus infection, a dengue virus infection, an influenza virus infection or an RSV virus infection, or a virus-associated condition.

[0048] [ka]

[0049] Where: m is 0, 1 or 2; R 3 represents a chlorine atom or a hydrogen atom, R is a (C1-C4) alkyl group, a (C3-C6) cycloalkyl group, a halogen atom, a (C1-C5) alkoxy group, -SO2-NR a R b group, -SO3H group, -OH group, -O-SO2-OR c Group or -OP(=O)-(OR c )(OR d ) group, R 1 teeth, (i) 3 CF groups, (ii) (C1-C 10 ) alkyl group, wherein the (C1-C 10 Optionally, one of the carbon atoms of the alkyl group may be replaced by an oxygen atom, and the (C1-C 10 ) the alkyl group may be optionally substituted by one or more of a -CF3 group, a halogen atom, in particular a fluorine atom, a pyridyl group, a phenyl group, a (C3-C6)cycloalkyl group, a (C3-C6)heterocycloalkyl group or a hydroxy group; (iii) a (C3-C6)cycloalkyl group or a (C3-C6)heterocycloalkyl group, which may be optionally substituted by one or two groups independently selected from a (C1-C2)alkyl group or a fluorine atom, or (iv) a phenyl group or a naphthyl group, wherein the groups are optionally selected from the group consisting of a (C1-C4) alkyl group, a halogen atom, a -COOR' group, a (C1-C5) alkoxy group, -SO2-NR a R b group, -SO3H group, -OH group, -O-SO2-OR c Group or -OP(=O)-(OR c )(OR d ) groups, and R 2 is a hydrogen atom, (C1-C 10 ) alkyl group, a (C3-C6) cycloalkyl group or a (C3-C6) heterocycloalkyl group, wherein the (C3-C6) cycloalkyl group or the (C3-C6) heterocycloalkyl group may be optionally substituted by one or two groups independently selected from a (C1-C2) alkyl group or a fluorine atom; OR 1 The group is in the para or meta position on the phenyl relative to the NH-group, R', R a and R b each independently represents a hydrogen atom, a (C1-C5) alkyl group, or a (C3-C6) cycloalkyl group, and R c and R d are independently hydrogen atoms, Li, Na, K, N(R a ) 4 or a benzyl group.

[0050] The above-mentioned compounds are particularly suitable for treating or preventing a viral infection or a viral-associated condition, in particular an RNA virus infection or a viral-associated condition caused by an RNA virus belonging to group IV or group V of the Baltimore classification, more preferably a chikungunya virus infection, a dengue virus infection, an influenza virus infection or an RSV virus infection or a viral-associated condition.

[0051] First perspective Accordingly, a subject of the present invention relates to a compound of formula (I), or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA virus infection caused by an RNA virus belonging to group IV or group V of the Baltimore classification, preferably an RSV virus infection, a Chikungunya virus infection, a Dengue virus infection and an Influenza virus infection, more particularly an RSV virus infection, a Chikungunya virus infection and a Dengue virus infection, even more preferably an RSV virus infection.

[0052] [ka]

[0053] Where: m is 0, 1 or 2; R 3 represents a chlorine atom or a hydrogen atom, R is a (C1-C4) alkyl group, a (C3-C6) cycloalkyl group, a halogen atom, a (C1-C5) alkoxy group, -SO2-NR a R b group, -SO3H group, -OH group, -O-SO2-OR c Group, or -OP(=O)-(OR c )(OR d ) group, R 1 teeth, (i) 3 CF groups, (ii) (C1-C 10 ) alkyl group, wherein the (C1-C 10Optionally, one of the carbon atoms of the alkyl group may be replaced by an oxygen atom, and the (C1-C 10 ) the alkyl group may be optionally substituted by one or more of a -CF3 group, a halogen atom, in particular a fluorine atom, a pyridyl group, a phenyl group, a (C3-C6)cycloalkyl group, a (C3-C6)heterocycloalkyl group or a hydroxy group; (iii) a (C3-C6)cycloalkyl group or a (C3-C6)heterocycloalkyl group, which may be optionally substituted by one or two groups independently selected from a (C1-C2)alkyl group or a fluorine atom; or (iv) a phenyl group or a naphthyl group, wherein the groups are optionally selected from the group consisting of a (C1-C4) alkyl group, a halogen atom, a -COOR' group, a (C1-C5) alkoxy group, -SO2-NR a R b group, -SO3H group, -OH group, -O-SO2-OR c Group or -OP(=O)-(OR c )(OR d ) groups, and R 2 is a hydrogen atom, (C1-C 10 ) alkyl group, a (C3-C6) cycloalkyl group or a (C3-C6) heterocycloalkyl group, wherein the (C3-C6) cycloalkyl group or the (C3-C6) heterocycloalkyl group may be optionally substituted by one or two groups independently selected from a (C1-C2) alkyl group or a fluorine atom; OR 1 The group is in the para or meta position on the phenyl relative to the NH-group, R', R a and R b each independently represents a hydrogen atom, a (C1-C5) alkyl group, or a (C3-C6) cycloalkyl group, and R c and R d are independently hydrogen atoms, Li, Na, K, N(R a ) 4 or a benzyl group, Where: R 2 and R 3 are both hydrogen atoms, R is different from a methoxy group, and OR 1 is different from a methoxy group or a benzyloxy group.

[0054] In one embodiment, the invention relates to the compounds of formula (I) as defined above, or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA viral infection caused by an RNA virus belonging to group IV or group V of the Baltimore classification, wherein m is 0 or 1.

[0055] According to another embodiment, the present invention relates to a compound of formula (I) as defined above, or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA viral infection caused by an RNA virus belonging to group IV or group V of the Baltimore classification, wherein R 3 represents a chlorine atom or a hydrogen atom.

[0056] According to another embodiment, the present invention relates to a compound of formula (I) as defined above, or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA viral infection caused by an RNA virus belonging to group IV or group V of the Baltimore classification, wherein R represents a (C1-C4) alkyl group, a (C3-C6) cycloalkyl group (i.e. when m is not 0).

[0057] According to another embodiment, the present invention relates to a compound of formula (I) as defined above, or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA viral infection caused by an RNA virus belonging to group IV or V of the Baltimore classification, wherein R 1 but, (i) 3 CF groups, (ii) (C1-C 10 ) alkyl group, wherein the (C1-C10 Optionally, one of the carbon atoms of the alkyl group may be replaced by an oxygen atom, and the (C1-C 10 ) the alkyl group is optionally substituted with one or more of a -CF3 group, a pyridyl group, a phenyl group, a (C3-C6)heterocycloalkyl group, or a hydroxy group; (iii) a (C3-C6) cycloalkyl group or a (C3-C6) heterocycloalkyl group, or (iv) a phenyl group or a naphthyl group, which may be optionally substituted by one or two groups independently selected from a (C1-C4) alkyl group, a halogen atom, a -COOR' group, a (C1-C5) alkoxy group or a -OH group; represents R' is a (C1-C5) alkyl group, and the OR 1 The group is in the para or meta position on the phenyl relative to the NH-group, Represents.

[0058] According to another embodiment, the present invention relates to a compound of formula (I) as defined above, or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA viral infection caused by an RNA virus belonging to group IV or group V of the Baltimore classification, wherein R 2 is a hydrogen atom, (C1-C 10 ) alkyl group or (C3-C6) cycloalkyl group.

[0059] m, R, R 1 , R 2 and R 3 Any combination of the above defined embodiments with one another forms part of the present invention.

[0060] According to a particular embodiment, the subject of the present invention relates to a compound of formula (I), or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA virus infection caused by an RNA virus belonging to group IV or V of the Baltimore classification, preferably an RSV virus infection, a Chikungunya virus infection, a Dengue virus infection and an Influenza virus infection, more particularly an RSV virus infection, a Chikungunya virus infection and a Dengue virus infection, even more preferably an RSV virus infection.

[0061] [ka]

[0062] Where: m is 0, 1 or 2; R 3 represents a chlorine atom or a hydrogen atom, R is a (C1-C4) alkyl group, a (C3-C6) cycloalkyl group, a halogen atom, a (C1-C5) alkoxy group, -SO2-NR a R b group, -SO3H group, -OH group, -O-SO2-OR c Group, or -OP(=O)-(OR c )(OR d ) group, R 1 teeth, (i) 3 CF groups, (ii) (C1-C 10 ) alkyl group, wherein the (C1-C 10 Optionally, one of the carbon atoms of the alkyl group may be replaced by an oxygen atom, and the (C1-C 10 ) the alkyl group may be optionally substituted by one or more of a -CF3 group, a halogen atom, in particular a fluorine atom, a pyridyl group, a phenyl group, a (C3-C6)cycloalkyl group, a (C3-C6)heterocycloalkyl group or a hydroxy group; (iii) a (C3-C6)cycloalkyl group or a (C3-C6)heterocycloalkyl group, which may be optionally substituted by one or two groups independently selected from a (C1-C2)alkyl group or a fluorine atom; or (iv) a phenyl group or a naphthyl group, wherein the groups are optionally selected from the group consisting of a (C1-C4) alkyl group, a halogen atom, a -COOR' group, a (C1-C5) alkoxy group, -SO2-NR a R b group, -SO3H group, -OH group, -O-SO2-OR c Group or -OP(=O)-(OR c )(OR d ) groups, and R 2 is (C1~C 10 ) alkyl group, a (C3-C6) cycloalkyl group or a (C3-C6) heterocycloalkyl group, wherein the (C3-C6) cycloalkyl group or the (C3-C6) heterocycloalkyl group may be optionally substituted by one or two groups independently selected from a (C1-C2) alkyl group or a fluorine atom; OR 1 The group is in the para or meta position on the phenyl relative to the NH-group, R', R a and R b each independently represents a hydrogen atom, a (C1-C5) alkyl group, or a (C3-C6) cycloalkyl group, and R c and R d are independently hydrogen atoms, Li, Na, K, N(R a ) 4 or a benzyl group.

[0063] According to a particular embodiment, a subject of the present invention relates to a compound of formula (I) as defined above, or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA viral infection caused by an RNA virus belonging to group IV or V of the Baltimore classification, in which m is 0 or 1 and R is a methyl group, and R 1 but, (i) 3 CF groups, (ii) a (C1-C6) alkyl group, in which one of the carbon atoms of the (C1-C6) alkyl group is optionally replaced by an oxygen atom, and the (C1-C6) alkyl group is optionally substituted by a -CF3 group, a pyridyl group, a phenyl group, a (C3-C6) heterocycloalkyl or a hydroxy group, or (iii) a (C3-C6)cycloalkyl group or a (C3-C6)heterocycloalkyl group, (iv) a phenyl group or a naphthyl group, which may be optionally substituted by one or two groups independently selected from a (C1-C4) alkyl group, a -COOR' group, a (C1-C4) alkoxy group, a hydroxy group or a halogen atom; represents R 2 represents a hydrogen atom or a (C1-C4) alkyl group; R' represents a (C1-C2) alkyl group.

[0064] According to a particular embodiment, a subject of the present invention relates to a compound of formula (I) as defined above, or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA virus infection caused by an RNA virus belonging to group IV or group V of the Baltimore classification, preferably an RSV virus infection, a Chikungunya virus infection, a Dengue virus infection and an Influenza virus infection, more particularly an RSV virus infection, a Chikungunya virus infection and a Dengue virus infection, and even more preferably an RSV virus infection, wherein m is 0 or 1 and R is a methyl group (i.e. when m is 1), and R1 but, (i) 3 CF groups, (ii) a (C1-C6) alkyl group, in which one of the carbon atoms of the (C1-C6) alkyl group is optionally replaced by an oxygen atom, and the (C1-C6) alkyl group is optionally substituted by a -CF3 group, a pyridyl group, a phenyl group, a (C3-C6) heterocycloalkyl or a hydroxy group, or (iii) a (C3-C6)cycloalkyl group or a (C3-C6)heterocycloalkyl group, (iv) a phenyl group or a naphthyl group, which may be optionally substituted by one or two groups independently selected from a (C1-C4) alkyl group, a -COOR' group, a (C1-C4) alkoxy group, a hydroxy group or a halogen atom; represents R 2 represents a hydrogen atom or a (C1-C4) alkyl group; R' represents a (C1-C2) alkyl group; Where: R 2 and R 3 If both are hydrogen atoms, then OR 1 is different from a methoxy group or a benzyloxy group.

[0065] The present invention describes a compound of the following formula (I), or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA virus infection from group IV or V of the Baltimore classification,

[0066] [ka]

[0067] Where: m is 0, 1 or 2; R 3 represents a chlorine atom or a hydrogen atom, R is a (C1-C4) alkyl group, a (C3-C6) cycloalkyl group, a halogen atom, a (C1-C5) alkoxy group, -SO2-NR a R b group, -SO3H group, -OH group, -O-SO2-OR c Group, or -OP(=O)-(OR c )(OR d ) group, R 1 teeth, (i) 3 CF groups, (ii) (C1-C 10 ) alkyl group, wherein the (C1-C 10 Optionally, one of the carbon atoms of the alkyl group may be replaced by an oxygen atom, and the (C1-C 10 ) the alkyl group may be optionally substituted by one or more of a -CF3 group, a halogen atom, in particular a fluorine atom, a pyridyl group, a phenyl group, a (C3-C6)cycloalkyl group, a (C3-C6)heterocycloalkyl group or a hydroxy group; (iii) a (C3-C6)cycloalkyl group or a (C3-C6)heterocycloalkyl group, which may be optionally substituted by one or two groups independently selected from a (C1-C2)alkyl group or a fluorine atom; or (iv) a phenyl group or a naphthyl group, wherein the groups are optionally selected from the group consisting of a (C1-C4) alkyl group, a halogen atom, a -COOR' group, a (C1-C5) alkoxy group, -SO2-NR a R b group, -SO3H group, -OH group, -O-SO2-OR c Group or -OP(=O)-(OR c )(OR d ) groups, and R 2 is a hydrogen atom, (C1-C 10) alkyl group, a (C3-C6) cycloalkyl group or a (C3-C6) heterocycloalkyl group, wherein the (C3-C6) cycloalkyl group or the (C3-C6) heterocycloalkyl group may be optionally substituted by one or two groups independently selected from a (C1-C2) alkyl group or a fluorine atom; OR 1 The group is in the para or meta position on the phenyl relative to the NH-group, R', R a and R b each independently represents a hydrogen atom, a (C1-C5) alkyl group, or a (C3-C6) cycloalkyl group, and R c and R d are independently hydrogen atoms, Li, Na, K, N(R a ) 4 or a benzyl group, Here, R 1 means (i) above, then R 2 is different from the methyl group, and R 1 When R denotes unsubstituted phenyl, 2 and R 3 is not a hydrogen atom.

[0068] According to a particular embodiment, the present invention relates to a compound of formula (I) as defined above, or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA virus infection caused by an RNA virus belonging to group IV or V of the Baltimore classification, preferably an RSV virus infection, a Chikungunya virus infection, a Dengue virus infection and an Influenza virus infection, more particularly an RSV virus infection, a Chikungunya virus infection and a Dengue virus infection, even more preferably an RSV virus infection,

[0069] [ka]

[0070] Where: m is 0, 1 or 2; R3 represents a chlorine atom or a hydrogen atom, R is a (C1-C4) alkyl group, a (C3-C6) cycloalkyl group, a halogen atom, a (C1-C5) alkoxy group, -SO2-NR a R b group, -SO3H group, -OH group, -O-SO2-OR c Group or -OP(=O)-(OR c )(OR d ) group, R 1 teeth, (i) 3 CF groups, (ii) (C1-C 10 ) alkyl group, wherein the (C1-C 10 Optionally, one of the carbon atoms of the alkyl group may be replaced by an oxygen atom, and the (C1-C 10 ) the alkyl group may be optionally substituted by one or more of a -CF3 group, a halogen atom, in particular a fluorine atom, a pyridyl group, a phenyl group, a (C3-C6)cycloalkyl group, a (C3-C6)heterocycloalkyl group or a hydroxy group; (iii) a (C3-C6)cycloalkyl group or a (C3-C6)heterocycloalkyl group, which may be optionally substituted by one or two groups independently selected from a (C1-C2)alkyl group or a fluorine atom, or (iv) a phenyl group or a naphthyl group, wherein the groups are optionally selected from the group consisting of a (C1-C4) alkyl group, a halogen atom, a -COOR' group, a (C1-C5) alkoxy group, -SO2-NR a R b group, -SO3H group, -OH group, -O-SO2-OR c Group or -OP(=O)-(OR c )(OR d ) groups, and R 2 is a hydrogen atom, (C1-C 10) alkyl group, a (C3-C6) cycloalkyl group or a (C3-C6) heterocycloalkyl group, wherein the (C3-C6) cycloalkyl group or the (C3-C6) heterocycloalkyl group may be optionally substituted by one or two groups independently selected from a (C1-C2) alkyl group or a fluorine atom; OR 1 The group is in the para or meta position on the phenyl relative to the NH-group, R', R a and R b each independently represents a hydrogen atom, a (C1-C5) alkyl group, or a (C3-C6) cycloalkyl group, and R c and R d are independently hydrogen atoms, Li, Na, K, N(R a ) 4 or a benzyl group, Here, R 1 means (i) above, then R 2 is different from the methyl group, and R 1 When R denotes unsubstituted phenyl, 2 and R 3 is not a hydrogen atom at the same time, Also, R 2 and R 3 and R are hydrogen atoms, R is different from a methoxy group, and OR 1 is different from a methoxy group or a benzyloxy group.

[0071] According to a preferred embodiment, the subject of the present invention relates to a compound of formula (I), or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA virus infection caused by an RNA virus belonging to group IV or V of the Baltimore classification, preferably an RSV virus infection, a Chikungunya virus infection, a Dengue virus infection and an Influenza virus infection, more particularly an RSV virus infection, a Chikungunya virus infection and a Dengue virus infection, and even more preferably an RSV virus infection,

[0072] [ka]

[0073] Where: m is 0, 1 or 2; R 3 represents a chlorine atom or a hydrogen atom, R is a (C1-C4) alkyl group, a (C3-C6) cycloalkyl group, a halogen atom, a (C1-C5) alkoxy group, -SO2-NR a R b group, -SO3H group, -OH group, -O-SO2-OR c Group or -OP(=O)-(OR c )(OR d ) group, R 1 teeth, (i) 3 CF groups, (ii) (C1-C 10 ) alkyl group, wherein the (C1-C 10 Optionally, one of the carbon atoms of the alkyl group may be replaced by an oxygen atom, and the (C1-C 10 ) the alkyl group may be optionally substituted by one or more of a -CF3 group, a halogen atom, in particular a fluorine atom, a pyridyl group, a phenyl group, a (C3-C6)cycloalkyl group, a (C3-C6)heterocycloalkyl group or a hydroxy group; (iii) a (C3-C6)cycloalkyl group or a (C3-C6)heterocycloalkyl group, which may be optionally substituted by one or two groups independently selected from a (C1-C2)alkyl group or a fluorine atom, or (iv) a phenyl group or a naphthyl group, wherein the groups are optionally selected from the group consisting of a (C1-C4) alkyl group, a halogen atom, a -COOR' group, a (C1-C5) alkoxy group, -SO2-NR a R b group, -SO3H group, -OH group, -O-SO2-OR c Group or -OP(=O)-(OR c )(OR d ) groups, and R 2 is (C1~C 10 ) alkyl group or a (C3-C6) cycloalkyl group, wherein the (C3-C6) cycloalkyl group may be optionally substituted by one or two groups independently selected from a (C1-C2) alkyl group or a fluorine atom, and preferably R 2 represents a methyl group, an ethyl group, an isobutyl group, a propyl group or a cyclopropyl group, and even more preferably, R 2 represents a cyclopropyl group. OR 1 The group is in the para or meta position on the phenyl relative to the NH-group, R', R a and R b each independently represents a hydrogen atom, a (C1-C5) alkyl group, or a (C3-C6) cycloalkyl group, and R c and R d are independently hydrogen atoms, Li, Na, K, N(R a ) 4 or a benzyl group.

[0074] According to a more preferred embodiment, the present invention relates to a compound of formula (I) as defined in the present invention, or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA virus infection caused by an RNA virus belonging to group IV or group V of the Baltimore classification, preferably an RSV virus infection, a Chikungunya virus infection, a Dengue virus infection and an Influenza virus infection, more particularly an RSV virus infection, a Chikungunya virus infection and a Dengue virus infection, and even more preferably an RSV virus infection, 2 represents a methyl group, an ethyl group, an isobutyl group or a propyl group.

[0075] According to an even more preferred embodiment, the present invention relates to a compound of formula (I) as defined in the present invention, or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA virus infection caused by an RNA virus belonging to group IV or group V of the Baltimore classification, preferably an RSV virus infection, a Chikungunya virus infection, a Dengue virus infection and an Influenza virus infection, more particularly an RSV virus infection, a Chikungunya virus infection and a Dengue virus infection, and even more preferably an RSV virus infection, wherein the compound is selected from compounds 1, 2, 3, 5, 6, 7, 9 to 19, 21 to 26, 38 to 41, 43, 45, 47 to 51, 53 to 59, 61, 63 to 71, 74 to 76, 78 and 79 as defined below.

[0076] According to an even more preferred embodiment, the present invention relates to a compound of formula (I) as defined in the present invention, or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prophylaxis of RNA viral infections caused by RNA viruses belonging to group IV or group V of the Baltimore classification, preferably RSV viral infections, chikungunya viral infections, dengue viral infections and influenza viral infections, more particularly RSV viral infections, chikungunya viral infections and dengue viral infections, even more preferably RSV viral infections, 2 represents a methyl group.

[0077] According to an even more preferred embodiment, the present invention relates to a compound of formula (I) as defined in the present invention, or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA virus infection caused by an RNA virus belonging to group IV or group V of the Baltimore classification, preferably an RSV virus infection, a Chikungunya virus infection, a Dengue virus infection and an Influenza virus infection, more particularly an RSV virus infection, a Chikungunya virus infection and a Dengue virus infection, and even more preferably an RSV virus infection, wherein the compound is selected from compounds 1, 5, 9, 10, 11, 12, 14 to 18, 21 to 26, 38, 40, 43, 45, 47 to 51, 53 to 59, 63 to 70 and 78 as defined below.

[0078] According to another even more preferred embodiment, the present invention relates to a compound of formula (I) as defined in the present invention, or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prophylaxis of an RNA virus infection caused by an RNA virus belonging to group IV or group V of the Baltimore classification, preferably an RSV virus infection, a Chikungunya virus infection, a Dengue virus infection and an Influenza virus infection, more particularly an RSV virus infection, a Chikungunya virus infection and a Dengue virus infection, and even more preferably an RSV virus infection, 2 represents a mecyclopropyl group.

[0079] According to an even more preferred embodiment, the present invention relates to a compound of formula (I) as defined in the present invention, or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA virus infection caused by an RNA virus belonging to group IV or group V of the Baltimore classification, preferably an RSV virus infection, a Chikungunya virus infection, a Dengue virus infection and an Influenza virus infection, more particularly an RSV virus infection, a Chikungunya virus infection and a Dengue virus infection, and even more preferably an RSV virus infection, wherein the compound is selected from compounds 4, 8, 20, 42, 44, 46, 52, 72 and 73 as defined below.

[0080] According to a particular embodiment, the present invention relates to a compound of formula (I) below, or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA virus infection caused by an RNA virus belonging to group IV or V of the Baltimore classification, preferably a Chikungunya virus infection, an RSV virus infection and / or a Dengue virus infection,

[0081] [ka]

[0082] Where: m is 0 or 1, R 3 represents a chlorine atom or a hydrogen atom, R represents a (C1-C4) alkyl group or a (C3-C6) cycloalkyl group; R 1 teeth, (i) 3 CF groups, (ii) (C1-C 10 ) alkyl group, wherein the (C1-C 10 Optionally, one of the carbon atoms of the alkyl group may be replaced by an oxygen atom, and the (C1-C 10 ) the alkyl group is optionally substituted with one or more of a -CF3 group, a pyridyl group, or a phenyl group; (iii) a (C3-C6) cycloalkyl group, or (iv) a phenyl group or a naphthyl group, which may be optionally substituted by one or two groups independently selected from a (C1-C4) alkyl group, a halogen atom, a (C1-C5) alkoxy group, or a -OH group; and R 2 is a hydrogen atom, (C1-C 10 ) alkyl group or (C3-C6) cycloalkyl group, OR 1 The group is in the para or meta position on the phenyl relative to the NH-group, Where: R 2 and R 3 If both are hydrogen atoms, then OR 1 is different from a methoxy group or a benzyloxy group.

[0083] According to another preferred embodiment, the present invention relates to a compound of formula (I) as defined above, or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA virus infection caused by an RNA virus belonging to group IV or group V of the Baltimore classification, preferably an RSV virus infection, a Chikungunya virus infection, a Dengue virus infection and an Influenza virus infection, more particularly an RSV virus infection, a Chikungunya virus infection and a Dengue virus infection, even more preferably an RSV virus infection and / or a Chikungunya virus infection, which is selected from compounds 1 to 8, 10, 12 to 14, 16, 17, 20 to 23, 28, 29, 31, 32, 38 to 57, 63, 76 and 77 as defined below.

[0084] According to a particular embodiment, the present invention relates to a compound of formula (I), or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA virus infection, preferably a Chikungunya virus infection, caused by an RNA virus belonging to group IV or V of the Baltimore classification,

[0085] [ka]

[0086] Where: m is 0 or 1; R 3 represents a chlorine atom or a hydrogen atom, R represents a (C1-C4) alkyl group; R 1 teeth, (i) 3 CF groups, (ii) (C1-C 10 ) alkyl group, wherein the (C1-C 10 Optionally, one of the carbon atoms of the alkyl group may be replaced by an oxygen atom, and the (C1-C 10 ) the alkyl group may be optionally substituted with one or more -CF3 or pyridyl groups; (iii) a (C3-C6) cycloalkyl group, or (iv) a phenyl group, wherein the phenyl group is optionally substituted by one or two groups independently selected from a (C1-C4) alkyl group, a halogen atom, or a (C1-C5) alkoxy group; and R 2 is a hydrogen atom, (C1-C 10 ) alkyl group or (C3-C6) cycloalkyl group, OR 1 The group is in the para or meta position on the phenyl relative to the NH-group, Where: R 2 and R 3 If both are hydrogen atoms, then OR 1 is different from a methoxy group.

[0087] According to another preferred embodiment, the present invention relates to a compound of formula (I) as defined above, or any one of its pharmaceutically acceptable salts, for use in the treatment and / or prevention of an RNA virus infection caused by an RNA virus belonging to group IV or group V of the Baltimore classification, preferably an RSV virus infection, a Chikungunya virus infection, a Dengue virus infection and an Influenza virus infection, more particularly an RSV virus infection, a Chikungunya virus infection and a Dengue virus infection, even more preferably a Chikungunya virus infection, which is selected from compounds 1 to 4, 6 to 8, 10, 12 to 14, 16, 17, 20 to 23, 29, 31, 32 and 38 to 46 as defined below.

[0088] According to a particular embodiment, the present invention relates to a compound of formula (I), or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA virus infection caused by an RNA virus belonging to group IV or V of the Baltimore classification, preferably an RSV virus infection,

[0089] [ka]

[0090] Where: m is 0 or 1; R 3 represents a chlorine atom or a hydrogen atom, R represents a (C1-C4) alkyl group or a (C3-C6) cycloalkyl group; R 1 teeth, (i) 3 CF groups, (ii) (C1-C 10 ) alkyl group, wherein the (C1-C 10 Optionally, one of the carbon atoms of the alkyl group may be replaced by an oxygen atom, and the (C1-C 10 ) the alkyl group may be optionally substituted with one or more phenyl groups; (iii) a (C3-C6)cycloalkyl group or a (C3-C6)heterocycloalkyl group, which may be optionally substituted by one or two groups independently selected from a (C1-C2)alkyl group or a fluorine atom, or (iii) a phenyl or naphthyl group, which may be optionally substituted by one or two groups independently selected from a halogen atom, a -COOR' group, a (C1-C5)alkoxy group, or a -OH group; and R 2 is a hydrogen atom, (C1-C 10 ) alkyl group or (C3-C6) cycloalkyl group, OR 1 The group is in the para or meta position on the phenyl relative to the NH-group, Where: R 2 and R 3 If both are hydrogen atoms, then OR 1 is different from a methoxy group or a benzyloxy group.

[0091] According to another preferred embodiment, the present invention relates to a compound of formula (I) as defined above, or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA virus infection caused by an RNA virus belonging to group IV or group V of the Baltimore classification, preferably an RSV virus infection, a Chikungunya virus infection, a Dengue virus infection and an Influenza virus infection, more particularly an RSV virus infection, a Chikungunya virus infection and a Dengue virus infection, even more preferably an RSV virus infection, which is selected from compounds 1, 6, 10, 13, 28, 38, 43, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56 and 57 as defined below.

[0092] According to a particular embodiment, the present invention relates to a compound of formula (I), or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA virus infection, preferably a Dengue virus infection, caused by an RNA virus belonging to group IV or V of the Baltimore classification,

[0093] [ka]

[0094] Where: m is 0 or 1; R 3 represents a chlorine atom or a hydrogen atom, R represents a (C1-C4) alkyl group; R 1 teeth, (i) 3 CF groups, (ii) (C1-C 10 ) alkyl group, wherein the (C1-C 10 Optionally, one of the carbon atoms of the alkyl group may be replaced by an oxygen atom, and the (C1-C 10 ) the alkyl group may be optionally substituted with one or more phenyl groups; (iii) a (C3-C6) cycloalkyl group, or (iv) a phenyl group or a naphthyl group, which may be optionally substituted by one or two groups independently selected from a halogen atom or a (C1-C5)alkoxy group; and R 2 is a hydrogen atom, (C1-C 10 ) alkyl group or (C3-C6) cycloalkyl group, OR 1 The group is in the para or meta position on the phenyl relative to the NH-group, Where: R 2 and R 3 If both are hydrogen atoms, then OR 1 is different from a methoxy group or a benzyloxy group.

[0095] According to another preferred embodiment, the present invention relates to a compound of formula (I) as defined above, or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA virus infection caused by an RNA virus belonging to group IV or group V of the Baltimore classification, preferably an RSV virus infection, a Chikungunya virus infection, a Dengue virus infection and an Influenza virus infection, more particularly an RSV virus infection, a Chikungunya virus infection and a Dengue virus infection, even more preferably a Dengue virus infection, which is selected from compounds 5, 10, 12, 13, 16, 20, 22, 39, 40, 42 to 44, 46, 47, 54, 56, 63, 76 and 77 as defined below.

[0096] According to another particular embodiment, the present invention relates to a compound of formula (I) as defined in the present invention, or any one of its pharma- ceutically acceptable salts, for use in the treatment and / or prevention of an RNA virus infection caused by an RNA virus belonging to group IV or V of the Baltimore classification, wherein the RNA virus infection caused by an RNA virus belonging to group IV or V of the Baltimore classification is selected among an RSV virus infection, a Chikungunya virus infection, a Dengue virus infection and an Influenza virus infection, more particularly selected among an RSV virus infection, a Chikungunya virus infection and a Dengue virus infection, and even more preferably an RSV virus infection.

[0097] The present invention further extends to the compounds themselves. Among the novel compounds, the compounds of formula (I) defined in the following groups 1 to 4 as defined below are relevant to the present invention.

[0098] It is a specific embodiment Group 1 According to the invention, a further subject is the compound of formula (I) as defined above, or any one of its pharma- ceutically acceptable salts, in which m, R 1 , R 3and R is as defined above, R 2 represents a (C3-C6)cycloalkyl group or a (C3-C6)heterocycloalkyl group, which may be optionally substituted by one or two groups independently selected from a (C1-C2)alkyl group or a fluorine atom.

[0099] It is a specific embodiment Group 2 Accordingly, an additional subject of the present invention is a compound of formula (I) or any one of its pharma- ceutically acceptable salts, in which R 1 but, (i) CF3 group, where R 2 is neither a hydrogen atom nor a methyl group, (ii) (C1-C 10 ) alkyl group, wherein the (C1-C 10 Optionally, one of the carbon atoms of the alkyl group may be replaced by an oxygen atom, and the (C1-C 10 ) The alkyl group may be optionally substituted by one or more of a -CF3 group, a halogen atom, in particular a fluorine atom, a pyridyl group, a phenyl group, a (C3-C6)cycloalkyl group, a (C3-C6)heterocycloalkyl group or a hydroxy group, provided that R 2 is not a hydrogen atom, or (iii) a (C3-C6)cycloalkyl group or a (C3-C6)heterocycloalkyl group, which may be optionally substituted by one or two (C1-C2)alkyl groups or fluorine atoms; Represents.

[0100] Still according to this particular embodiment, R 1 is preferably (i) or (ii) above.

[0101] Another specific embodiment Group 3 Accordingly, an additional subject of the present invention is a compound of formula (I) or any one of its pharma- ceutically acceptable salts, in which m, R, R 2 and R 3is as defined above, and R 1 but, (i) (C1~C 10 ) alkyl group, wherein the (C1-C 10 Optionally, one of the carbon atoms of the alkyl group may be replaced by an oxygen atom, and the (C1-C 10 ) the alkyl group may be optionally substituted by one or more of the following: -CF3 group, a halogen atom, in particular a fluorine atom, a pyridyl group, a phenyl group, a (C3-C6)cycloalkyl group or a (C3-C6)heterocycloalkyl group or a hydroxy group; However, R 1 includes a (C3-C6)cycloalkyl group or a (C3-C6)heterocycloalkyl group, or (ii) a (C3-C6)cycloalkyl group or a (C3-C6)heterocycloalkyl group, which may be optionally substituted by one or two (C1-C2)alkyl groups or fluorine atoms; Represents.

[0102] In the above embodiment (group 3), in item (i), the expression "wherein R 1 includes a (C3-C6)cycloalkyl group or a (C3-C6)heterocycloalkyl group" means, in the sense of the present invention, that R 1 (C1~C 10 When the alkyl group represents the (C1-C 10 ) alkyl group must contain at least one substituent selected from among (C3-C6) cycloalkyl and (C3-C6) heterocycloalkyl groups.

[0103] Another specific embodiment Group 4 According to the invention, a further subject is the compound of formula (I) as defined above, or any one of its pharma- ceutically acceptable salts, in which m, R 2 , R 3 , R', R a , R b , R c , R dand R is as defined above, and R 1 is optionally a (C1-C4) alkyl group, a halogen atom, a -COOR' group, a (C1-C5) alkoxy group, -SO2-NR a R b group, -SO3H group, -OH group, -O-SO2-OR c Group or -OP(=O)-(OR c )(OR d a naphthyl group optionally substituted by one or two groups independently selected from the group consisting of (C1-C4) alkyl groups, halogen atoms, -COOR' groups, (C1-C5) alkoxy groups, -SO2-NR a R b group, -SO3H group, -OH group, -O-SO2-OR c Group or -OP(=O)-(OR c )(OR d ) groups.

[0104] Another specific embodiment Group 5 According to the invention, a further subject is the compound of formula (I) as defined above, or any one of its pharma- ceutically acceptable salts, in which m, R 2 and R 3 is as defined above, and R 1 teeth, (i) (C1~C 10 ) alkyl group, wherein the (C1-C 10 Optionally, one of the carbon atoms of the alkyl group may be replaced by an oxygen atom, and the (C1-C 10 ) the alkyl group may be optionally substituted by one or more of a -CF3 group, a halogen atom, in particular a fluorine atom, a pyridyl group, a phenyl group, a (C3-C6)cycloalkyl group, a (C3-C6)heterocycloalkyl group or a hydroxy group; However, R 1 includes a (C3-C6)cycloalkyl group or a (C3-C6)heterocycloalkyl group, or (ii) a (C3-C6)cycloalkyl group or a (C3-C6)heterocycloalkyl group, which may be optionally substituted by one or two groups independently selected from a (C1-C2)alkyl group or a fluorine atom; represents Where: R 2 and R 3 are both hydrogen atoms, R is different from a methoxy group, and OR 1 is different from a methoxy group or a benzyloxy group.

[0105] In the above embodiment (group 5), in item (i), the expression "wherein R 1 includes a (C3-C6)cycloalkyl group or a (C3-C6)heterocycloalkyl group" means, in the sense of the present invention, that R 1 (C1~C 10 When the alkyl group represents the (C1-C 10 ) alkyl group must contain at least one substituent selected from among (C3-C6) cycloalkyl and (C3-C6) heterocycloalkyl groups.

[0106] Certain such compounds relate to novel compounds of formula (I).

[0107] According to a preferred embodiment of the present invention, the compounds of formula (I) for use in the treatment and / or prevention of RNA virus infections caused by RNA viruses belonging to group IV or V of the Baltimore classification, preferably RSV virus infections, Chikungunya virus infections, Dengue virus infections and Influenza virus infections, more particularly RSV virus infections, Chikungunya virus infections and Dengue virus infections, even more preferably RSV virus infections, are selected from: (1) 8-Chloro-N-(2-methyl-4-(trifluoromethoxy)phenyl)quinolin-2-amine (2) 8-Chloro-N-(2-ethyl-4-(trifluoromethoxy)phenyl)quinolin-2-amine (3) 8-Chloro-N-(2-isobutyl-4-(trifluoromethoxy)phenyl)quinolin-2-amine (4) 8-Chloro-N-(2-cyclopropyl 4-(trifluoromethoxy)phenyl)quinolin-2-amine (5) 8-Chloro-N-(2-ethyl-6-methyl-4-(trifluoromethoxy)phenyl)quinolin-2-amine (6) 8-Chloro-N-(2-propyl-4-(trifluoromethoxy)phenyl)quinolin-2-amine (7) N-(2-ethyl-4-(trifluoromethoxy)phenyl)quinolin-2-amine (8) N-(2-cyclopropyl 4-(trifluoromethoxy)phenyl)quinolin-2-amine (9) 8-Chloro-N-(4-methoxy-2-methylphenyl)quinolin-2-amine (10) 8-Chloro-N-(4-isopropoxy-2-methylphenyl)quinolin-2-amine (11) 8-Chloro-N-(4-(2-methoxyethoxy)-2-methylphenyl)quinolin-2-amine (12) 8-Chloro-N-(4-ethoxy-2-methylphenyl)quinolin-2-amine (13) 8-Chloro-N-(2-ethyl-4-isopropoxyphenyl)quinolin-2-amine (14) 8-Chloro-N-(2-methyl-4-(2-(trifluoromethoxy)ethoxy)phenyl)quinolin-2-amine (15) 8-Chloro-N-(4-isopropoxy-2,6-dimethylphenyl)quinolin-2-amine (16) 8-Chloro-N-(4-(cyclopentyloxy)-2-methylphenyl)quinolin-2-amine (17) 8-Chloro-N-(4-(cyclohexyloxy)-2-methylphenyl)quinolin-2-amine (18) 2-(4-((8-chloroquinolin-2-yl)amino)-3-methylphenoxy)ethanol (19) N-(2-ethyl-4-isopropoxyphenyl)quinolin-2-amine (20) 8-Chloro-N-(2-cyclopropyl-4-isopropoxyphenyl)quinolin-2-amine (21) 8-Chloro-N-(4-isopropoxy-2,3-dimethylphenyl)quinolin-2-amine (22) 8-Chloro-N-(4-cyclobutoxy-2-methylphenyl)quinolin-2-amine (23) 8-Chloro-N-(2-methyl-4-(pyridin-2-ylmethoxy)phenyl)quinolin-2-amine (24) 8-Chloro-N-(2-methyl-4-(pyridin-4-ylmethoxy)phenyl)quinolin-2-amine (25) 8-Chloro-N-(2-methyl-4-((3-methyloxetan-3-yl)methoxy)phenyl)quinolin-2-amine (26) 8-Chloro-N-(2-methyl-4-(oxetan-3-yloxy)phenyl)quinolin-2-amine (27) N-(4-phenoxyphenyl)quinolin-2-amine (28) N-(4-(p-tolyloxy)phenyl)quinolin-2-amine (29) N-(4-(2-fluorophenoxy)phenyl)quinolin-2-amine (30) 2-(4-(quinolin-2-ylamino)phenoxy)benzoic acid methyl ester (31) 8-Chloro-N-(4-(p-tolyloxy)phenyl)quinolin-2-amine (32) 8-Chloro-N-(4-(2-fluorophenoxy)phenyl)quinolin-2-amine (33) 2-(4-((8-chloroquinolin-2-yl)amino)phenoxy)benzoic acid methyl ester (34) N-(4-(4-chlorophenoxy)phenyl)quinolin-2-amine (35) N-(4-(4-fluorophenoxy)phenyl)quinolin-2-amine (36) 8-Chloro-N-(4-(4-chlorophenoxy)phenyl)quinolin-2-amine (37) 8-Chloro-N-(4-(4-fluorophenoxy)phenyl)quinolin-2-amine (38) N-(4-(2-fluorophenoxy)-2-methylphenyl)quinolin-2-amine (39) N-(2-ethyl-4-(2-fluorophenoxy)phenyl)quinolin-2-amine (40) 8-Chloro-N-(4-isopropoxy-5-isopropyl 2-methylphenyl)quinolin-2-amine (41) 8-Chloro-N-(4-cyclobutoxy-2-ethylphenyl)quinolin-2-amine (42) 8-Chloro-N-(4-cyclobutoxy-2-cyclopropylphenyl)quinolin-2-amine (43) 8-Chloro-N-(4-isopropoxy-2,5-dimethylphenyl)quinolin-2-amine (44) 8-Chloro-N-(4-(cyclopentyloxy)-2-cyclopropylphenyl)quinolin-2-amine (45) N-(4-(2-fluoro-4-methoxyphenoxy)-2-methylphenyl)quinolin-2-amine (46) N-(2-cyclopropyl 4-(2-fluorophenoxy)phenyl)quinolin-2-amine (47) N-(4-(benzyloxy)-2-methylphenyl)-8-chloroquinolin-2-amine (48) 8-Chloro-N-(5-cyclopropyl 4-isopropoxy-2-methylphenyl)quinolin-2-amine (49) 8-Chloro-N-(3-isopropoxy-2-methylphenyl)quinolin-2-amine (50) N-(3-(benzyloxy)-2-methylphenyl)-8-chloroquinolin-2-amine (51) N-(4-(4-methoxyphenoxy)-2-methylphenyl)quinolin-2-amine (52) N-(2-cyclopropyl 4-(2-fluoro-4-methoxyphenoxy)phenyl)quinolin-2-amine (53) 3-Fluoro-4-(3-methyl-4-(quinolin-2-ylamino)phenoxy)phenol (54) 8-Chloro-N-(2-methyl-4-(naphthalen-1-yloxy)phenyl)quinolin-2-amine (55) 8-Chloro-N-(2-methyl-3-phenoxyphenyl)quinolin-2-amine (56) 8-Chloro-N-(2-methyl-4-phenoxyphenyl)quinolin-2-amine 2,2,2-trifluoroacetate (57) 8-Chloro-N-(2-methyl-4-(naphthalen-2-yloxy)phenyl)quinolin-2-amine (58) N-(2-methyl-3-phenoxyphenyl)quinolin-2-amine (59) 8-Chloro-N-(2-methyl-3-(pyridin-3-ylmethoxy)phenyl)quinolin-2-amine (60) 8-Chloro-N-(3-phenoxyphenyl)quinolin-2-amine (61) 8-Chloro-N-(2-methyl-5-phenoxyphenyl)quinolin-2-amine (62) 8-Chloro-N-(4-phenoxyphenyl)quinolin-2-amine (63) 8-Chloro-N-(4-(2-fluorophenoxy)-2,5-dimethylphenyl)quinolin-2-amine 2,2,2-trifluoroacetate (64) 8-Chloro-N-(2,6-dimethyl-4-phenoxyphenyl)quinolin-2-amine (65) N-(4-isopropoxy-2,5-dimethylphenyl)quinolin-2-amine (66) N-(2,6-dimethyl-4-phenoxyphenyl)quinolin-2-amine (67) N-(4-isopropoxy-2-methylphenyl)quinolin-2-amine (68) N-(2-methyl-4-phenoxyphenyl)quinolin-2-amine (69) 2-(3-((8-chloroquinolin-2-yl)amino)-4-methylphenoxy)ethanol (70) 2-(3-((8-chloroquinolin-2-yl)amino)-2-methylphenoxy)ethanol (71) 8-Chloro-N-(2-methyl-6-propyl-4-(trifluoromethoxy)phenyl)quinolin-2-amine (72) 8-Chloro-N-(2-cyclopropyl-6-methyl-4-(trifluoromethoxy)phenyl)quinolin-2-amine (73) N-(2-cyclopropyl 4-isopropoxyphenyl)quinolin-2-amine (74) N-(4-isopropoxy-2-propylphenyl)quinolin-2-amine (75) N-(2-propyl-4-(trifluoromethoxy)phenyl)quinolin-2-amine (76) N-(2-ethyl-4-(2-fluoro-4-methoxyphenoxy)phenyl)quinolin-2-amine (77) N-(4-(2-fluoro-4-methoxyphenoxy)phenyl)quinolin-2-amine (78) 8-Chloro-N-(5-isopropoxy-2-methylphenyl)quinolin-2-amine (79) 2-(4-((8-chloroquinolin-2-yl)amino)-3-propylphenoxy)ethanol and pharma-ceutically acceptable salts thereof.

[0108] The present invention therefore extends to compounds (2) to (26) and (28) to (79) as defined above and their pharma- ceutically acceptable salts, such as the hydrobromides, tartrates, citrates, trifluoroacetates, ascorbates, hydrochlorides, tosylates, triflates, maleates, mesylates, formates, acetates and fumarates.

[0109] In another aspect, the subject of the invention relates to a novel compound of formula (I) as defined above, or any one of its pharma- ceutically acceptable salts, or at least any one of compounds (2) to (26) and (28) to (79), more preferably any one of 2 to 8, 10, 12 to 14, 16, 17, 20 to 23, 28, 29, 31, 32, 38 to 57, 63, 76 and 77, or a pharma- ceutically acceptable salt thereof, for use as a medicament.

[0110] In another aspect of the invention, a subject of the invention relates to the novel compounds of formula (I) as defined above, or any one of their pharmaceutically acceptable salts, or at least one of the compounds (1) to (79), more preferably compounds 1 to 8, 10, 12 to 14, 16, 17, 20 to 23, 28, 29, 31, 32, 38 to 57, 63, 76 and 77, or any one of their pharmaceutically acceptable salts, for use as an agent for preventing, inhibiting or treating an RNA virus infection caused by an RNA virus belonging to group IV or group V of the Baltimore classification, preferably an RSV virus infection, a chikungunya virus infection, a dengue virus infection and an influenza virus infection, more particularly an RSV virus infection, a chikungunya virus infection and a dengue virus infection, even more preferably an RSV virus infection.

[0111] The compounds of the present invention may exist in the form of a free base or in the form of an addition salt with a pharma- ceutically acceptable acid.

[0112] "Pharmaceutically acceptable salts thereof" refers to salts formed from acid addition salts formed with inorganic acids (e.g., hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, and the like) as well as salts formed from acid addition salts formed with organic acids, such as acetic acid, oxalic acid, tartaric acid, succinic acid, malic acid, fumaric acid, maleic acid, ascorbic acid, benzoic acid, tannic acid, palmoic acid, alginic acid, polyglutamic acid, naphlenesulfonic acid, naphlendisulfonic acid, and polygalacturonic acid.

[0113] Suitable physiologically acceptable acid addition salts of compounds of formula (I) include hydrobromides, tartrates, citrates, trifluoroacetates, ascorbates, hydrochlorides, tosylates, triflates, maleates, mesylates, formates, acetates and fumarates.

[0114] The compound of formula (I), and any one of the compounds (1) to (79), or any one of the pharma-ceutically acceptable salts thereof, may form solvates or hydrates, and the present invention includes all such solvates and hydrates.

[0115] The compounds of formula (I) may also exist in tautomeric forms and are also part of the invention.

[0116] The terms "hydrate" and "solvate" simply mean that the compound (I) according to the invention can be in the form of a hydrate or solvate, i.e. combined or associated with one or more water or solvent molecules. This is merely a chemical property of such compounds, which can be applied to all organic compounds of this type.

[0117] In the context of the present invention: The term "halogen" is understood to mean a chlorine, fluorine, bromine or iodine atom, and in particular denotes a chlorine, fluorine or bromine atom. As used herein, the term "(C1-C x )Alkyl" are C1 to C x "C1-C6" refers to a primary, secondary, or tertiary saturated hydrocarbon, such as (C1-C6) alkyl. Examples include, but are not limited to, methyl, ethyl, 1-propyl, 2-propyl, butyl, and pentyl. As used herein, the term "(C3-C6)cycloalkyl" refers to a cyclic saturated hydrocarbon. Examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. As used herein, the term "(C3-C6)heterocycloalkyl group" refers to a (C3-C6)cycloalkyl group, in which one or two of the carbon atoms are replaced by a heteroatom, such as an oxygen atom or a nitrogen atom. Examples include, but are not limited to, morpholine, piperazine, piperidine, pyrrolidine, aziridine, oxetane, furan, and dioxane. As used herein, the term "(C1-C x "(C1-Cx)alkoxy" refers to an O-(C1-Cx)alkyl moiety, where alkyl is as defined above, such as (C1-C6)alkoxy. Examples include, but are not limited to, methoxy, ethoxy, 1-propoxy, 2-propoxy, butoxy and pentoxy.

[0118] The compounds of formula (I) may contain one or more asymmetric carbon atoms. They may therefore exist in enantiomeric or diastereomeric forms. These enantiomers, diastereomers and mixtures thereof, including racemic mixtures, are included within the scope of the present invention.

[0119] The compounds of the present invention can be prepared by conventional methods of organic synthesis practiced by those skilled in the art. The general reaction sequences outlined below represent general methods useful for preparing the compounds of the present invention and are not meant to be limiting in scope or usefulness.

[0120] Compounds of general formula (I) can be prepared according to Scheme 1 below.

[0121] [ka] Scheme 1

[0122] The synthesis is based on a coupling reaction starting from an amino aromatic compound of formula (II) above, where R, m, R 1 and R 2is as defined above and the chloroaromatic compound of formula (III) is as defined above.

[0123] According to route (A), the compound of formula (III) may be placed in a protic solvent, such as tert-butanol, and then the compound of formula (II) may be added in the presence of an inorganic base, such as Cs2CO3 or K2CO3, for example in a molar ratio of 1 to 1.5 relative to the compound of formula (III), or in the presence of a diphosphine, such as Xantphos (4,5-bis(diphenylphosphino)-9,9-dimethylxanthene) or X-Phos (2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl), for example in a molar ratio of 1 to 5, in particular in an amount of 2 mol% to 15 mol% relative to the total amount of the compound of formula (III) and in the presence of an organometallic catalyst, such as Pd(OAc)2 or Pd2dba3, in an amount of 2 mol% to 25 mol% relative to the total amount of the compound of formula (III). The reaction mixture can then be heated at a temperature of 80-130°C, for example 90°C, and stirred under an inert gas, for example argon, for 13-90 hours, for example 24 hours. The reaction mixture can be concentrated under reduced pressure, and the residue can be diluted with an organic solvent, for example ethyl acetate. The organic phase can be washed with water, decanted, dried over magnesium sulfate, filtered, concentrated under reduced pressure, and then purified to give the compound of formula (I).

[0124] As an alternative to following route (A), the compound of formula (III) can be placed in an aprotic solvent, such as anhydrous 1,4-dioxane. Then, the compound of formula (II) can be added in the presence of an inorganic acid, such as hydrochloric acid (e.g. 4N HCl in 1,4-dioxane), in a molar ratio of, for example, 1 to 1.5, such as a molar ratio of 2 to 7, relative to the compound of formula (III). The reaction mixture can then be heated under microwave irradiation at a temperature of 100 to 190° C., such as 170° C., and stirred for 10 to 120 minutes, such as 45 minutes. The reaction mixture can be filtered, concentrated under reduced pressure, and then purified to give the compound of formula (I).

[0125] Starting compounds of formula (II), formula (III) are available or can be prepared according to methods known to those skilled in the art.

[0126] The present invention therefore further relates to a synthetic process for preparing the novel compounds of formula (I) as defined above, comprising the steps of: A compound of formula (II)

[0127] [ka] with a compound of formula (III)

[0128] [ka]

[0129] in the presence of an inorganic base and a diphosphine and in the presence of an organometallic catalyst to obtain a compound of formula (I), Here, R 1 , R 2 , R 3 , R and m are as defined above. The above relates to the method.

[0130] More particularly, R 1 represents an alkyl group and R 2 When is different from H, is used to prepare a compound of formula (I), a compound of formula (II) can be prepared according to Scheme 2 below.

[0131] [ka]

[0132] The intermediate compounds of formula (II), formula (IV) and formula (V) above are useful for preparing compounds of formula (I) according to the present invention.

[0133] According to route (B), the 4-nitrophenol derivative can be placed in a polar solvent, such as N,N-dimethylformamide. The bromo derivative, R 1 Br, can be added in the presence of an inorganic base, such as Cs2CO3 or K2CO3, in a molar ratio of, for example, 1-2, in particular, 1-5, relative to the 4-nitrophenol derivative. The reaction mixture can then be heated at a temperature of 50-150°C, for example at 90°C, and stirred under an inert gas, such as argon, for 5-90 hours, for example 14 hours. The reaction mixture can be concentrated under reduced pressure, and the residue can be partitioned between an organic solvent, such as dichloromethane, and water. The organic phase can be washed with water, decanted, dried over magnesium sulfate, filtered, concentrated under reduced pressure, and purified to give the compound of formula (V).

[0134] According to route (C), a compound of formula (V) and an organometallic catalyst, such as Pd(dppf)Cl2.CH2Cl2, in an amount of, for example, 2 mol % to 20 mol % relative to the amount of the compound of formula (V), can be placed in a non-polar solvent, such as 1,4-dioxane. Then, a boronic acid, R 2 -B(OH)2, in the presence of an inorganic base, such as K3PO4 or K2CO3, may be added in a molar ratio of 1 to 5, particularly 2 to 5, relative to the compound of formula (V). The reaction mixture may then be heated at a temperature of 50 to 150°C, for example at 100°C, and stirred under an inert gas, such as argon, for 10 to 70 hours, for example 20 hours. The reaction mixture may be concentrated under reduced pressure and purified to give the compound of formula (IV).

[0135] According to route (D), the compound of formula (IV) and tin(II) chloride dihydrate in a ratio of 3-8 equivalents can be placed in a protic solvent, such as ethanol. The reaction mixture can then be heated at a temperature of 40-80° C., such as 60° C., and stirred for 15-25 hours, such as 14 hours. The mixture can be poured into a 1N aqueous solution of NaOH and extracted with an organic solvent, such as ethyl acetate. The organic phase can then be washed with water and a saturated aqueous solution of brine, dried over magnesium sulfate, filtered, concentrated under reduced pressure, and purified to give the compound of formula (II).

[0136] More particularly, R 1 represents an aryl group and R 2 When is different from H, is used to prepare a compound of formula (I), a compound of formula (II) can be prepared according to Scheme 3 or Scheme 4 below.

[0137] [ka]

[0138] The intermediate compounds of formula (II), formula (IV) and formula (V) above are useful for preparing compounds of formula (I) according to the present invention.

[0139] According to route (E), the 4-fluoronitrobenzene derivative can be placed in a polar solvent, such as N,N-dimethylformamide. Then, the phenol derivative, R 1OH, can be added in the presence of an inorganic base, such as Cs2CO3 or K2CO3, in a molar ratio of 1 to 2, in particular in a molar ratio of 1 to 5, relative to the 4-fluoronitrobenzene derivative. The reaction mixture can then be heated at a temperature of 50 to 150°C, for example at 70°C, and stirred under an inert gas, such as argon, for 5 to 90 hours, for example 16 hours. The reaction mixture can be concentrated under reduced pressure, and the residue can be partitioned between an organic solvent, such as dichloromethane, and water. The organic phase can be washed with water, decanted, dried over magnesium sulfate, filtered, concentrated under reduced pressure, and purified to give the compound of formula (V).

[0140] According to route (C), a compound of formula (V) and a compound organometallic catalyst, such as Pd(dppf)Cl2.CH2Cl2, in an amount of, for example, 2 mol % to 20 mol % relative to the compound of formula (V), can be placed in a non-polar solvent, such as 1,4-dioxane. Then, a boronic acid, R 2 -B(OH)2, in the presence of an inorganic base, such as K3PO4 or K2CO3, may be added in a molar ratio of 1 to 5, particularly 2 to 5, relative to the compound of formula (V). The reaction mixture may then be heated at a temperature of 50 to 150°C, for example at 100°C, and stirred under an inert gas, such as argon, for 10 to 70 hours, for example 20 hours. The reaction mixture may be concentrated under reduced pressure and purified to give the compound of formula (IV).

[0141] According to route (D), the compound of formula (IV) and tin(II) chloride dihydrate in a ratio of 3-8 equivalents can be placed in a protic solvent, such as ethanol. The reaction mixture can then be heated at a temperature of 40-80° C., such as 60° C., and stirred for 15-25 hours, such as 14 hours. The mixture can be poured into a 1N aqueous solution of NaOH and extracted with an organic solvent, such as ethyl acetate. The organic phase can then be washed with water and a saturated aqueous solution of brine, dried over magnesium sulfate, filtered, concentrated under reduced pressure, and purified to give the compound of formula (II).

[0142] [ka]

[0143] The intermediate compounds of formula (II) above are useful for preparing compounds of formula (I) according to the present invention.

[0144] According to route (F), the halogenoaryl derivative, R 1 X, can be placed in a non-polar solvent, such as toluene. The phenol derivative can then be reacted with compound R in the presence of an inorganic base, such as Cs2CO3 or K2CO3, in a molar ratio of 1 to 2 relative to the halogenoaryl derivative, in the presence of a ligand, such as 1-methylimidazole, in a molar ratio of 1 to 3, in the presence of a copper catalyst, such as CuCl or CuI. 1 Compound R in an amount of 5 mol % to 30 mol % based on the total amount of X 1 X may be added in an amount of 2 mol % to 15 mol % relative to the total amount of X. The reaction mixture may then be heated at a temperature of 50 to 150° C., for example at 130° C., and stirred under an inert gas, for example argon, for 5 to 25 hours, for example 16 hours. The reaction mixture may be filtered through a pad of Celite. The filtrate may be concentrated under reduced pressure, and the residue may be purified to give a compound of formula (II).

[0145] The chemical structures and spectroscopic data of some compounds of formula (I) of the present invention are shown in the following Tables I and II, respectively.

[0146] [Table 1] JPEG0007673362000018.jpg255124JPEG0007673362000019.jpg255123JPEG0007673362000020.jpg255123JPEG000 7673362000021.jpg255121JPEG0007673362000022.jpg255125JPEG0007673362000023.jpg255121JPEG00076733620 00024.jpg255130JPEG0007673362000025.jpg255127JPEG0007673362000026.jpg255127JPEG0007673362000027.j pg255129JPEG0007673362000028.jpg255130JPEG0007673362000029.jpg255127JPEG0007673362000030.jpg116124

[0147] [Table 2] JPEG0007673362000032.jpg251170JPEG0007673362000033.jpg251170JPEG0007673362000034.jpg249170JPEG0007673362000035.jpg242170 JPEG0007673362000036.jpg249170JPEG0007673362000037.jpg252170JPEG0007673362000038.jpg255170JPEG0007673362000039.jpg116170

[0148] The following examples are offered by way of illustration and are not intended to limit the scope of the invention in any way.

[0149] The following examples detail the preparation of some compounds according to the invention. The structures of the products obtained are confirmed by NMR spectroscopy.

[0150] Working Example

[0151] Example 1: Compound (2) in Table I

[0152] According to route (C), 2-bromo-4-trifluoromethoxyaniline (2.3 mL, 15 mmol, 1 equiv.) was placed in 1,4-dioxane (55 mL) with Pd(dppf)Cl2.CH2Cl2 (1.2 g, 1.5 mmol, 0.1 equiv.). Upon addition of Cs2CO3 (19.6 g, 60 mmol, 4 equiv.) and ethylboronic acid (3.3 g, 45 mmol, 3 equiv.), the reaction mixture was heated at 100° C. and stirred for 14 h under an inert atmosphere. The reaction mixture was then concentrated under reduced pressure and the resulting residue was purified by column chromatography on silica gel to give 2-ethyl-4-(trifluoromethoxy)aniline (1.3 g, 42%).

[0153] 1 H NMR (300MHz, CDCl3) δ 6.93(s,1H),6.90(d,J=8.5Hz,1H),6.63(d,J=8.5Hz,1H),3.64(s,2H),2.49(q,J=7.5Hz,2H),1.25(t,J=7.5Hz,3H).

[0154] According to route (A), a reaction mixture of 2,8-dichloroquinoline (1.16 g, 5.85 mmol, 1.0 equiv.), 2-ethyl-4-(trifluoromethoxy)aniline (1.20 g, 5.85 mmol, 1.0 equiv.), Pd(OAc)2 (53 mg, 0.23 mmol, 4 mol %), XantPhos (133 mg, 0.23 mmol, 4 mol %) and Cs2CO3 (5.46 g, 16.75 mmol, 2.9 equiv.) in t-BuOH (23.4 mL) was heated at 90° C. for 3 days. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the resulting residue was diluted with dichloromethane. The organic phase was then washed with water, dried over MgSO4, filtered and concentrated under reduced pressure to give a residue which was purified by column chromatography on silica gel to give, after trituration in cyclohexane, a fraction which afforded 8-chloro-N-[2-ethyl-4-(trifluoromethoxy)phenyl]quinolin-2-amine (2) (626 mg, 29%).

[0155] 1 H NMR(300MHz,CDCl3) δ 7.96(d,J=9.0Hz,1H),7.91(d,J=9.0Hz,1H),7.72(dd,J=8.0,1.0Hz,1H),7.57(dd,J=8.0,1.0Hz,1H),7.21(t,J =8.0Hz,1H),7.15~7.13(m,2H),6.83(d,J=9.0Hz,1H),6.74(s,1H),2.71(q,J=7.5Hz,2H),1.26(t,J=7.5Hz,3H).

[0156] 13 C NMR(75MHz,CDCl3) δ 153.1,143.7,141.6,136.3,136.0,133.5,127.9,127.6,124.1,122.9,122.3,120.5,119.1,116.9,109.2,22.0,11.4

[0157] [M+H] + =367.2

[0158] Example 2 Compound (4) in Table I

[0159] According to route (C), 2-bromo-4-trifluoromethoxyaniline (1.5 mL, 10 mmol, 1 equiv.) was placed in 1,4-dioxane (36 mL) with Pd(dppf)Cl2.CH2Cl2 (817 mg, 1 mmol, 0.1 equiv.). Upon addition of K3PO4 (8.5 g, 40 mmol, 4 equiv.) and cyclopropylboronic acid (2.6 g, 30 mmol, 3 equiv.), the reaction mixture was heated at 100° C. and stirred under inert atmosphere for 16 h. The reaction mixture was then concentrated under reduced pressure and the resulting residue was purified by column chromatography on silica gel to give 2-cyclopropyl 4-(trifluoromethoxy)aniline (1.09 g, 50%).

[0160] 1 H NMR (300MHz, CDCl3) δ 6.90(d,J=7.0Hz,2H),6.62(dd,J=7.0,2.0Hz,1H),3.97(s,2H),1.71~1.62(m,1H),0.93(m,2H),0.60(m,2H).

[0161] According to route (A), a reaction mixture of 2,8-dichloroquinoline (638 mg, 3.22 mmol, 1.0 equiv.), 2-cyclopropyl 4-(trifluoromethoxy)aniline (700 mg, 3.22 mmol, 1.0 equiv.), Pd(OAc)2 (29 mg, 0.13 mmol, 4 mol %), XantPhos (73 mg, 0.13 mmol, 4 mol %) and Cs2CO3 (3.0 g, 9.23 mmol, 2.9 equiv.) in t-BuOH (12.9 mL) was heated at 90° C. for 3 days under an inert atmosphere. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the resulting residue was diluted with dichloromethane. The organic phase was then washed with water, dried over MgSO4, filtered and concentrated under reduced pressure to give a residue which was purified by column chromatography on silica gel to give, after trituration in cyclohexane, a fraction which afforded 8-chloro-N-[2-cyclopropyl 4-(trifluoromethoxy)phenyl]quinolin-2-amine (4) (322 mg, 26%).

[0162] 1 H NMR(300MHz,CDCl3) δ 8.73(d,J=9.0Hz,1H),7.95(d,J=9.0Hz,1H),7.74(dd,J=8.0,1.2Hz,1H),7.58(dd,J=8.0,1.2Hz,1H),7.35(s,1H),7.22(d,J=8.0Hz,1H),7 .17(d,J=2.0Hz,1H),7.01(d,J=2.0Hz,1H),6.92(d,J=9.0Hz,1H),1.91(tt,J=8.3,5.4Hz,1H),1.07(q,J=4.3Hz,2H),0.74(q,J=4.3Hz,2H).

[0163] 13 C NMR(75MHz,CDCl3) δ 152.1,142.2,141.8,136.2,136.0,131.4,128.8,127.9,124.3,123.2,121.1,118.9,118.8,117.8,117.6,111.2,9.5,4.4

[0164] [M+H] + =379.1

[0165] Example 3 Compound (16) in Table I

[0166] According to route (B), 4-nitro-5-methylphenol (1.5 g, 10 mmol, 1 equiv.) was placed in N,N-dimethylformamide (8 mL) with K2CO3 (4.2 g, 30 mmol, 3 equiv.). Upon addition of bromocyclopentane (2.1 mL, 20 mmol, 2 equiv.), the reaction mixture was heated at 50° C. and stirred for 4 days under inert atmosphere. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the resulting residue was partitioned between ethyl acetate and water. Upon decantation, the organic phase was washed with a saturated aqueous solution of brine, dried over MgSO4, filtered, and concentrated under reduced pressure to give 4-(cyclopentyloxy)-2-methyl-1-nitrobenzene (1.8 g, 81%).

[0167] 1 H NMR (300MHz, CDCl3) δ 8.14~8.02(m,1H),6.80~6.72(m,2H),4.85~4.80(m,1H),2.62(s,3H),2.01~1.78(m,6H),1.75~1.57(m,3H).

[0168] According to route (D), 4-(cyclopentyloxy)-2-methyl-1-nitrobenzene (1.8 g, 8.1 mmol, 1 equiv.) and tin(II) chloride dihydrate (9.2 g, 40.7 mmol, 5 equiv.) were placed in EtOH (81 mL). The reaction mixture was heated at 60° C. and stirred for 14 h under an inert atmosphere. The reaction mixture was then concentrated under reduced pressure and the resulting residue was diluted with ethyl acetate. The organic phase was washed with 1N NaOH aqueous solution, then with a saturated aqueous solution of brine, dried over MgSO4, filtered, and concentrated under reduced pressure to give 4-(cyclopentyloxy)-2-methylaniline (1.4 g, 90%).

[0169] 1H NMR (300MHz, CDCl3) δ 6.61(t,J=7.6Hz,3H),4.65~4.61(m,1H),3.33(s,2H),2.62(s,3H),2.01~1.78(m,6H),1.75~1.57(m,3H).

[0170] According to route (A), a reaction mixture of 2,8-dichloroquinoline (297 mg, 1.5 mmol, 1.5 equiv), 4-(cyclopentyloxy)-2-methylaniline (191 mg, 1.0 mmol, 1 equiv), Pd(OAc)2 (9 mg, 0.04 mmol, 4 mol%), XantPhos (23 mg, 0.04 mmol, 4 mol%) and Cs2CO3 (912 mg, 2.8 mmol, 2.8 equiv) in t-BuOH (4 mL) was heated at 90° C. for 14 h under an inert atmosphere. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the resulting residue was diluted with ethyl acetate. The organic phase was then washed with water, dried over MgSO, filtered and concentrated under reduced pressure, and the resulting residue was purified by column chromatography on silica gel to give 8-chloro-N-[4-(cyclopentyloxy)-2-methylphenyl]quinolin-2-amine (16) (94 mg, 27%).

[0171] 1 H NMR(300MHz,CDCl3) δ 7.83(d,J=9.0Hz,1H),7.69(dd,J=8.0,1.0Hz,1H),7.53(dd,J=8.0,1.0Hz,1H),7.37(d,J=8.5Hz,1H),7.15(t,J=8.0Hz,1H),6.82( d,J=2.7Hz,1H),6.76(dd,J=8.5,2.7Hz,1H),6.72(s,1H),6.67(d,J=9.0Hz,1H),4.85~4.72(m,1H),2.26(s,3H),1.97~1.75(m,8H).

[0172] [M+H] + =353.0

[0173] Example 4 Compound (20) in Table I

[0174] According to route (B), 3-bromo-4-nitrophenol (2.2 g, 10 mmol, 1 equiv.) was placed in N,N-dimethylformamide (17 mL) with K2CO3 (4.2 g, 30 mmol, 3 equiv.). Upon addition of 2-bromopropane (1.9 mL, 20 mmol, 2 equiv.), the reaction mixture was heated at 90° C. and stirred for 14 h under an inert atmosphere. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the resulting residue was partitioned between ethyl acetate and water. Upon decantation, the organic phase was washed with a saturated aqueous solution of brine, dried over MgSO4, filtered, and concentrated under reduced pressure to give 2-bromo-1-nitro-4-(propan-2-yloxy)benzene (2.3 g, 88%).

[0175] 1 H NMR (300MHz, CDCl3) δ 7.98(d,J=9.1Hz,1H),7.19(d,J=2.6Hz,1H),6.87(dd,J=9.1,2.6Hz,1H),4.63(hept,J=6.1Hz,1H),1.38(d,J=6.1Hz,6H).

[0176] According to route (C), 2-bromo-1-nitro-4-(propan-2-yloxy)benzene (2.3 g, 8.8 mmol, 1 equiv.) was placed in 1,4-dioxane (32 mL) with Pd(dppf)Cl2.CH2Cl2 (708 mg, 0.9 mmol, 0.1 equiv.). Upon addition of K3PO4 (7.5 g, 35 mmol, 4 equiv.) and cyclopropylboronic acid (2.3 g, 27 mmol, 3 equiv.), the reaction mixture was heated at 100° C. and stirred under inert atmosphere for 3 days. The reaction mixture was then concentrated under reduced pressure and the resulting residue was purified by column chromatography on silica gel to give 2-cyclopropyl-1-nitro-4-(propan-2-yloxy)benzene (1.5 g, 77%).

[0177] 1H NMR(300MHz,CDCl3) δ 7.95(d,J=9.1Hz,1H),6.72(dd,J=9.1,2.7Hz,1H),6.58(d,J=2.7Hz,1H),4.61(hep t,J=6.1Hz,1H),2.59~2.50(m,1H),1.36(d,J=6.1Hz,6H),1.05(m,2H),0.69(m,2H).

[0178] According to route (D), 2-cyclopropyl-1-nitro-4-(propan-2-yloxy)benzene (1.5 g, 6.8 mmol, 1 equiv.) and tin(II) chloride dihydrate (7.7 g, 34 mmol, 5 equiv.) were placed in EtOH (68 mL). The reaction mixture was heated at 60° C. and stirred for 14 h under an inert atmosphere. The reaction mixture was then concentrated under reduced pressure and the resulting residue was diluted with dichloromethane. The organic phase was washed with 1N aqueous NaOH solution, then with a saturated aqueous solution of brine, dried over MgSO4, filtered, and concentrated under reduced pressure to give 2-cyclopropyl-4-(propan-2-yloxy)aniline (1.2 g, 93%).

[0179] 1 H NMR(300MHz,CDCl3) δ 6.65~6.58(m,3H),4.36(hept,J=6.1Hz,1H),3.69(s,2H),1.73~1.64(m,1H),1.28(d,J=6.1Hz,6H),0.89(m,2H),0.59(m,2H).

[0180] According to route (A), a reaction mixture of 2,8-dichloroquinoline (828 mg, 4.18 mmol, 1.0 equiv.), 2-cyclopropyl 4-(propan-2-yloxy)aniline (800 mg, 4.18 mmol, 1.0 equiv.), Pd(OAc)2 (38 mg, 0.17 mmol, 4 mol %), XantPhos (95 mg, 0.17 mmol, 4 mol %) and Cs2CO3 (3.9 g, 12.0 mmol, 2.9 equiv.) in t-BuOH (17 mL) was heated at 90° C. for 14 h under an inert atmosphere. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the resulting residue was diluted with dichloromethane. The organic phase was then washed with water, dried over MgSO4, filtered and concentrated under reduced pressure, and the resulting residue was purified by column chromatography on silica gel to give 8-chloro-N-[2-cyclopropyl 4-(propan-2-yloxy)phenyl]quinolin-2-amine (20) (626 mg, 42%).

[0181] 1 H NMR(300MHz,CDCl3) δ 7.85(d,J=9.0Hz,1H),7.77(d,J=9.0Hz,1H),7.69(dd,J=8.0,1.2Hz,1H),7 .53(dd,J=8.0,1.2Hz,1H),7.16(t,J=8.0Hz,1H),7.05(s,1H),6.79(dd,J=9 .0,4.1Hz,2H),6.58(d,J=2.7Hz,1H),4.53(hept,J=6.1Hz,1H),2.02~1.93 (m,1H),1.34(d,J=6.1Hz,6H),0.94(q,J=4.3Hz,2H),0.68(q,J=4.3Hz,2H).

[0182] 13 C NMR(75MHz,CDCl3) δ 154.1,153.0,141.9,135.5,129.1,127.5,127.4,124.1,122.9,122.6,119.8,117.3,112.0,110.8,109.3,67.7,19.7,9.1,5.2

[0183] [M+H] +=353.2

[0184] Example 5 Compound (22) in Table I

[0185] According to route (B), 4-nitro-5-methylphenol (1.5 g, 10 mmol, 1 equiv.) was placed in N,N-dimethylformamide (8 mL) with K2CO3 (4.2 g, 30 mmol, 3 equiv.). Upon addition of cyclobutyl bromide (1.9 mL, 20 mmol, 2 equiv.), the reaction mixture was heated at 90° C. and stirred for 14 h under an inert atmosphere. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the resulting residue was partitioned between ethyl acetate and water. Upon decantation, the organic phase was washed with a saturated aqueous solution of brine, dried over MgSO4, filtered, and concentrated under reduced pressure to give 4-cyclobutoxy-2-methyl-1-nitrobenzene (1.8 g, 89%).

[0186] 1 H NMR(300MHz,CDCl3) δ 8.08~8.02(m,1H),6.72~6.63(m,2H),4.70(p,J=7.1Hz,1H),2.61(s,3H),2 .53~2.43(m,2H),2.28~2.10(m,2H),1.98~1.83(m,1H),1.81~1.65(m,1H).

[0187] According to route (D), 4-cyclobutoxy-2-methyl-1-nitrobenzene (1.0 g, 4.8 mmol, 1 equiv.) and tin(II) chloride dihydrate (5.4 g, 23.9 mmol, 5 equiv.) were placed in EtOH (48 mL). The reaction mixture was heated at 60° C. and stirred for 14 h under an inert atmosphere. The reaction mixture was then concentrated under reduced pressure and the resulting residue was diluted with dichloromethane. The organic phase was washed with 1N NaOH aqueous solution, then with a saturated aqueous solution of brine, dried over MgSO4, filtered, and concentrated under reduced pressure to give 4-cyclobutoxy-2-methylaniline (846 mg, 99%).

[0188] 1 H NMR(300MHz,CDCl3) δ 6.60~6.58(m,2H),6.55~6.51(m,1H),4.53(p,J=6.9Hz,1H),3.33(s,2H),2.45~2 .34(m,2H),2.14(s,3H),2.13~2.05(m,2H),1.88~1.75(m,1H),1.70~1.53(m,1H).

[0189] According to route (A), a reaction mixture of 2,8-dichloroquinoline (297 mg, 1.5 mmol, 1 equiv.), 4-cyclobutoxy-2-methylaniline (266 mg, 1.5 mmol, 1 equiv.), Pd(OAc)2 (14 mg, 0.06 mmol, 4 mol %), XantPhos (34 mg, 0.06 mmol, 4 mol %) and Cs2CO3 (1.4 g, 4.3 mmol, 2.9 equiv.) in t-BuOH (6 mL) was heated at 90° C. for 14 days under an inert atmosphere. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the resulting residue was diluted with dichloromethane. The organic phase was then washed with water, dried over MgSO4, filtered and concentrated under reduced pressure, and the resulting residue was purified by column chromatography on silica gel to give 8-chloro-N-(4-cyclobutoxy-2-methylphenyl)quinolin-2-amine (22) (248 mg, 49%).

[0190] 1 H NMR (300MHz, CDCl3) δ 7.82(d,J=8.6Hz,1H),7.68(dd,J=8.0,1.2Hz,1H),7.52(dd,J=8.0,1.2Hz,1 H),7.38(d,J=8.6Hz,1H),7.15(t,J=7.8Hz,1H),6.76(d,J=2.8Hz,1H),6.71 (s,1H),6.68(t,J=7.8Hz,2H),4.64(p,J=7.0Hz,1H),2.53~2.40(m,2H),2.2 6(s,3H),2.23~2.10(m,2H),1.95~1.80(m,1H),1.71(tt,J=10.2,5.2Hz,1H).

[0191] 13C NMR(75MHz,CDCl3) δ 154.7,153.4,141.9,135.9,133.3,127.8,127.5,127.3,124.9,124.2,122.6,119.8,115.0,110.7,108.2,69.2,28.4,16.1,10.9

[0192] Example 6 Compound (38) in Table I

[0193] According to route (E), 2-fluorophenol (1.8 g, 16 mmol, 1 equiv.) was placed in N,N-dimethylformamide (50 mL) with K2CO3 (4.5 g, 32 mmol, 2 equiv.). Upon addition of 4-fluoro-2-methyl-1-nitrobenzene (2.5 g, 16 mmol, 1 equiv.), the reaction mixture was heated at 70° C. and stirred under inert atmosphere for 3 days. Upon cooling to room temperature, the reaction mixture was partitioned between ethyl acetate and water. Upon decantation, the organic phase was washed with a saturated aqueous solution of brine, dried over MgSO4, filtered, and concentrated under reduced pressure, and the resulting residue was purified by column chromatography on silica gel to give 4-(2-fluorophenoxy)-2-methyl-1-nitrobenzene (2.8 g, 70%).

[0194] 1 H NMR (300MHz, CDCl3) δ 8.05 (d, J=8.7Hz, 1H), 7.28~7.13 (m, 4H), 6.86~6.78 (m, 2H), 2.60 (s, 3H).

[0195] According to route (D), 4-(2-fluorophenoxy)-2-methyl-1-nitrobenzene (2.8 g, 11.3 mmol, 1 equiv.) and tin(II) chloride dihydrate (7.7 g, 34.0 mmol, 3 equiv.) were placed in EtOH (91 mL). The reaction mixture was heated at 60° C. and stirred for 20 h under an inert atmosphere. The reaction mixture was then concentrated under reduced pressure and the resulting residue was diluted with ethyl acetate. The organic phase was washed with 1N aqueous NaOH solution, then with a saturated aqueous solution of brine, dried over MgSO4, filtered and concentrated under reduced pressure and the resulting residue was purified by column chromatography on silica gel to give 4-(2-fluorophenoxy)-2-methylaniline (1.5 g, 61%).

[0196] 1 H NMR(300MHz,CDCl3) δ 7.17~7.10(m,1H),7.02~6.97(m,2H),6.93~6.87(m,1H),6.78(d,J=2.7Hz,1H), 6.74(dd,J=8.5,2.7Hz,1H),6.64(d,J=8.5Hz,1H),3.50(brs,2H),2.15(s,3H).

[0197] According to route (A), a reaction mixture of 2-chloroquinoline (527 mg, 3.22 mmol, 1 equiv.), 4-(2-fluorophenoxy)-2-methylaniline (700 mg, 3.22 mmol, 1 equiv.), Pd(OAc)2 (15 mg, 0.06 mmol, 2 mol %), XantPhos (37 mg, 0.06 mmol, 2 mol %) and Cs2CO3 (2.9 g, 9.0 mmol, 2.8 equiv.) in t-BuOH (13 mL) was heated at 90° C. for 16 h under an inert atmosphere. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the resulting residue was diluted with dichloromethane. The organic phase was then washed with water, dried over MgSO4, filtered and concentrated under reduced pressure, and the resulting residue was purified by column chromatography on silica gel to give N-[4-(2-fluorophenoxy)-2-methylphenyl]quinolin-2-amine (38) (385 mg, 35%).

[0198] 1 H NMR(300MHz,CDCl3) δ 7.88(d,J=8.9Hz,1H),7.69(d,J=8.2Hz,1H),7.63(d,J=8.2Hz,1H),7.60~7.53(m,1H),7.49(d,J=8.6Hz,1H),7.30 ~7.06(m,2H),6.93(d,J=2.7Hz,1H),6.86(dd,J=8.6,2.7Hz,1H),6.75(d,J=8.9Hz,1H),6.59(s,1H),2.27(s,3H).

[0199] 13 C NMR(75MHz,CDCl3) δ 153.5,152.2,145.4,141.5,141.4,135.5,132.5,130.8,127.4,125.1,123.9,123.7 ,122.4,122.3,122.2,121.5,120.3,119.3,117.2,114.8,114.5,113.2,107.8,15.9

[0200] [M+H] + =345.2

[0201] Example 7 Compound (46) in Table I

[0202] According to route (E), 2-fluorophenol (1.8 g, 16 mmol, 1 equiv.) was placed in N,N-dimethylformamide (50 mL) with K2CO3 (4.5 g, 32 mmol, 2 equiv.). Upon addition of 2-bromo-4-fluoro-1-nitrobenzene (3.5 g, 16 mmol, 1 equiv.), the reaction mixture was heated at 70° C. and stirred for 16 h under an inert atmosphere. Upon cooling to room temperature, the reaction mixture was partitioned between ethyl acetate and water. Upon decantation, the organic phase was washed with a saturated aqueous solution of brine, dried over MgSO4, filtered, and concentrated under reduced pressure, and the resulting residue was purified by column chromatography on silica gel to give 2-bromo-4-(2-fluorophenoxy)-1-nitrobenzene (3.8 g, 77%).

[0203] 1 H NMR(300MHz, CDCl3) δ 7.95(d,J=9.1Hz,1H),7.30~7.15(m,5H),6.95(dd,J=9.1,2.6Hz,1H).

[0204] According to route (C), 2-bromo-4-(2-fluorophenoxy)-1-nitrobenzene (1.0 g, 3.2 mmol, 1 equiv.) was placed in 1,4-dioxane (12 mL) with Pd(dppf)Cl2.CH2Cl2 (262 mg, 0.1 mmol, 0.1 equiv.). Upon addition of K3PO4 (2.7 g, 12.8 mmol, 4 equiv.) and cyclopropylboronic acid (826 mg, 9.6 mmol, 3 equiv.), the reaction mixture was heated at 100° C. and stirred for 20 h under an inert atmosphere. The reaction mixture was then concentrated under reduced pressure and the resulting residue was purified by column chromatography on silica gel to give 2-cyclopropyl 4-(2-fluorophenoxy)-1-nitrobenzene (830 mg, 95%).

[0205] 1 H NMR (300MHz, CDCl3) δ 7.90(d,J=9.6Hz,1H),7.26~7.11(m,4H),6.74~6.69(m,2H),2.56~2.47(m,1H),1.11~1.01(m,2H),0.73~0.61(m,2H).

[0206] According to route (D), 2-cyclopropyl 4-(2-fluorophenoxy)-1-nitrobenzene (830 mg, 3.0 mmol, 1 equiv.) and tin(II) chloride dihydrate (3.4 g, 15.2 mmol, 5 equiv.) were placed in EtOH (30 mL). The reaction mixture was heated at 60° C. and stirred for 14 h under an inert atmosphere. The reaction mixture was then concentrated under reduced pressure and the resulting residue was diluted with ethyl acetate. The organic phase was washed with 1N NaOH aqueous solution, then with a saturated aqueous solution of brine, dried over MgSO4, filtered, and concentrated under reduced pressure to give 2-cyclopropyl 4-(2-fluorophenoxy)aniline (736 mg, 100%).

[0207] 1 H NMR(300MHz,CDCl3) δ 7.18~7.10(m,1H),7.03~6.95(m,2H),6.91~6.84(m,1H),6.78~6.71(m,2H),6.64(d,J =8.4Hz,1H),3.85(brs,2H),1.74~1.63(m,1H),0.93~0.87(m,2H),0.61~0.55(m,2H).

[0208] According to route (A), a reaction mixture of 2-chloroquinoline (164 mg, 1.0 mmol, 1 equiv.), 2-cyclopropyl 4-(2-fluorophenoxy)aniline (243 mg, 1.0 mmol, 1 equiv.), Pd(OAc)2 (9 mg, 0.04 mmol, 4 mol %), XantPhos (23 mg, 0.04 mmol, 4 mol %) and Cs2CO3 (933 mg, 2.9 mmol, 2.9 equiv.) in t-BuOH (4 mL) was heated at 90° C. for 14 h under an inert atmosphere. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the resulting residue was diluted with dichloromethane. The organic phase was then washed with water, dried over MgSO4, filtered and concentrated under reduced pressure, and the resulting residue was purified by column chromatography on silica gel to give N-[2-cyclopropyl 4-(2-fluorophenoxy)phenyl]quinolin-2-amine (46) (121 mg, 33%).

[0209] 1 H NMR(300MHz,CDCl3) δ 7.88(d,J=8.9Hz,1H),7.80(d,J=8.7Hz,1H),7.73(d,J=8.2Hz,1H),7.62(d,J=8.2Hz,1H),7.59~7.54(m,1H),7.29~7.24(m,1H),7.21~7. 15(m,1H),7.12~7.00(m,2H),6.88~6.81(m,2H),6.77(d,J=2.8Hz,1H),1.95(tt,J=8.4,5.4Hz,1H),1.01~0.85(m,2H),0.69~0.60(m,2H).

[0210] 13 C NMR(75MHz,CDCl3) δ 155.8,155.4,153.7,147.8,144.5,144.4,144.3,137.8,137.6,134.8,129.9,127.5,126.5,124.7,124 .6,124.5,124.4,124.1,124.0,122.9,121.2,117.2,116.9,116.5,115.6,111.2,100.0,80.3,11.7,7.2

[0211] [M+H] + =371.2

[0212] Pharmacological Data Example 8: Chikungunya virus The compounds of the invention have been the subject of pharmacological tests which have demonstrated their relevance as active substances in therapy, in particular for preventing, inhibiting or treating Chikungunya virus infection.

[0213] Materials and Methods

[0214] Inhibition of Chikungunya virus (CHIKV) production in infected HEK293T cell lines The ability of the compounds to inhibit viral replication was evaluated in experiments where infected cells were tested with 1 μM of a compound of formula (I). Ribavirin was used as a positive control for inhibition of chikungunya. The toxicity of the compounds was evaluated in parallel.

[0215] · Cell proliferation Human embryonic kidney cells 293T (HEK293T, CRL-11268) were maintained in Dulbecco's modified Eagle's Medium (DMEM, 31966-021, Thermo Fisher Scientific) supplemented with 10% fetal bovine serum (FBS), penicillin, and streptomycin. After removing the medium, the cells were incubated with Ca 2+ and Mg 2+ The cells were then washed with 0.25% trypsin-EDTA solution to remove all traces of serum. After aspirating the wash, the cells were dissociated with 0.25% trypsin-EDTA solution and incubated for at least 30 seconds in a 37°C incubator. The concentration of the cell suspension was measured with an automated cell counter (EVE, NanoEntek) and, where necessary, adjusted to a concentration of 0.33 × 10 in DMEM medium supplemented with 10% FBS. 6 Adjusted to cells / mL.

[0216] · Preparation of compounds 100 μL of cell suspension was dispatched to ViewPlate-96 Black (6005182, PerkinElmer) and clear 96-well cell culture plates (655180, Greiner bio-one). After incubation at 37°C under 5% CO2 for 24 hours, compounds were added at appropriate concentrations.

[0217] · Screening at 1μM Intermediate dilutions were prepared from the stock solution in 96-well V-bottom microplates using DMSO (D8418, Sigma) at 2 mM. Mix 1 μL of 50 mM stock library in 25 μL of DMSO 2 μL of 25 mM stock library mixed in 25 μL of DMSO

[0218] · I C 50 Determining Values Intermediate dilutions were prepared from the stock solution in 96-well V-bottom microplates using DMSO (D8418, Sigma) at 25 mM. 2 μL of 50 mM stock library mixed with 2 μL of DMSO

[0219] Serial dilutions were performed 13 times in 2 μL of DMSO to arrive at 0.0015 mM as in Table III below.

[0220] [Table 3]

[0221] Screening and IC 50 For both determinations, 1 μL of each solution was added to 1 mL of Masterblock 96-well (Greiner bio-one, 780261) containing 1 mL of DMEM medium. As a positive control, 5 μL of 80 mM Ribavirin solution (R9644, Sigma) was added to 1 mL of DMEM, while DMSO was used as a negative control.

[0222] · infection Cells were infected with 30 μL of a CHIKV strain (LR2006-OPY1) originating from La Reunion modified with GFP at the 5' (CHIK 5'LR) (Tsetsarkin K, Higgs S, McGee CE, De Lamballerie X, Charrel RN, Vanlandingham DL. Infectious Clones of Chikungunya Virus (La Reunion solate- Ref-SKU:001N-EVA249 (PMID: 17187566).Vector Borne Zoonotic Dis.2006;6(4)). The modified virus was used to infect cells at an MOI of 0.1. CHIKV strain LR2006-OPY1 (CHIKV-LR) was obtained from the World Reference Center for Arboviruses at the University of Texas Medical Branch, Galveston, Texas. The strain was originally isolated from serum of a febrile French patient returning from La Réunion island.

[0223] · Cell lysis The medium was removed after 22 hours at 37°C under 5% CO2, and the cells were washed as above. 60μL of RIPA buffer (50mM Tris-HCl pH8, 100mM NaCl, 1mM MgCl2, 1% Triton X-100) was added to the cells and incubated for at least 20 minutes, and the fluorescent signal was read. Pierce 660nm Protein Assay Reagent (22660, Thermo scientific) was used to normalize the fluorescent signal by protein amount.

[0224] CellTiter 96® Aqueous One Solution Cell Proliferation Assay (MTS) (G3581, Promega) was used to check the toxicity of the compounds. We added 20 μL of MTS solution and read the absorbance at 492 nm after 1 hour.

[0225] result First round of experiments is performed, where the results are expressed as a percentage of inhibition calculated as follows: 1. Fluorescence intensity (FI) / absorbance at 660 nm (A660) = A This ratio makes it possible to take into account the amount of infection (GFP virus) relative to the amount of protein. 2. A' = A - background noise of uninfected plate 3.B = Fluorescence intensity (FI) / Absorbance at 660 nm (A660) of infected but untreated plate. 4. C=A' / B, which is then converted as the infection percentage after treatment compared to the untreated sample, and subsequently converted as the infection percentage. For example, a value of 100 in Table IV herein below means that after treatment, the signal due to GFP fluorescence disappears, which correlates to the absence of infection. 5. C'=100-C

[0226] This value corresponds to the percentage of inhibition.

[0227] Table IV below contains the above C' values ​​for several compounds, averaged over two experiments, and the corresponding standard deviations, as calculated above.

[0228] Some values ​​were originally above 100. In these cases, the values ​​were lowered to 100. This means that some molecules also affect cell viability. In other words, the A value can be lower than the background noise.

[0229] Furthermore, for each measurement, the test was performed with ribavirin as a control, and the inhibition percentage values ​​were checked and assigned a value of 100%.

[0230] [Table 4]

[0231] Second experiment The results are then compared with the IC 50 was given as.

[0232] I C 50The values ​​are between 0.1 nM and 1 μM, in particular between 0.5 and 500 nM, even more particularly between 1 and 400 nM, for example between 1 and 200 nM. For example, compounds 2, 4, 6, 10, 13, 16, 17, 20, 21, 22, 38, 39, 40, 41, 42, 43, 44, 45 and 46 have IC values ​​between 1 and 200 nM. 50 It has a value.

[0233] conclusion Based on the previous results it can be concluded that the compounds of formula (I) are suitable compounds for treating and / or preventing RNA virus infections caused by group IV RNA viruses, more particularly alphavirus infections, most particularly Chikungunya virus infections.

[0234] Example 9: RSV virus The compounds according to the invention have been the subject of pharmacological tests which have demonstrated their relevance as active substances in therapy, in particular for preventing, inhibiting or treating RSV viral infections.

[0235] Materials and Methods

[0236] Protocol for screening antiviral compounds for RSV inhibition and cytotoxicity using the viral ToxGlo assay HEp-2 cells were maintained in Eagle's minimum essential medium (EMEM) containing Earle's BSS adjusted to contain 2 mM L-glutamine, 10% fetal bovine serum, 100 U / ml penicillin, and 100 μg / ml streptomycin. For the purposes of the screening assay, they were grown to 90% confluency, trypsinized, and harvested. Trypsin was neutralized with cell culture medium, cells were centrifuged at 150 x g for 5 min, and the supernatant was discarded and the cell pellet was resuspended in assay medium (EMEM containing Earle's BSS adjusted to contain 2 mM L-glutamine, 2% fetal bovine serum, and 100 U / ml penicillin and 100 μg / ml streptomycin). Cells were plated at 1.5x10 in 50μl in white clear bottom cell culture plates in 96-well and 384-well plates, respectively. 4 4x10 cells / well and 25 μl 3 Cells were seeded at a density of 1000 cells / well. Only medium / background control column assay medium was added. The cell plates were placed in a humidified chamber and incubated overnight at 37°C / 5% CO2. After overnight incubation, cells were checked for confluency and healthy appearance.

[0237] Test articles were made up at 10x the test concentration with a maximum DMSO concentration of 10% (final assay concentration of DMSO up to 1%) and added to cell plates in volumes of 10 μl for 96-well plates and 5 μl for 384-well plates. For cell and virus control wells, only test article solvent was added. Assay medium for virus or cytotoxicity test wells and media / cell control wells was added immediately after test article at an MOI of 0.5, 40 or 20 μl for 96-well and 384-well plates, respectively. Virus suspensions were prepared by thawing RSV A2 frozen stocks and diluting to the required concentration of plaque forming units with assay medium on ice.

[0238] The cell plates were further incubated at 37°C / 5% CO2 in a humidified chamber for 72 hours pi. After the incubation period, the cells were observed under a microscope to check for characteristic cytopathic effects in virus control wells and healthy cells in cell control wells. After the plates were adjusted to room temperature, 20 / 40 μl of Viral ToxGlo (Promega) was added to each well of the 384 / 96-well cell plates. The plates were incubated at room temperature and luminescence was measured in a spectrophotometer (Biotek Synergy HTX) for 20 minutes protected from light on a plate rocker.

[0239] RSV inhibition was calculated as the percentage of cytopathic effect inhibition relative to virus control and cytotoxicity was calculated as the percentage of cell viability relative to cell control wells. This represents the EC for each test article at which a virus inhibition or cytotoxicity dose response was observed. 50 This allows the calculation of EC values ​​from 0.001 μM to 5 μM. 50 Values ​​were found for compounds 1, 6, 10, 13, 28, 38, 43, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56 and 57.

[0240] [Table 5]

[0241] conclusion Based on the above results, it can be concluded that the compounds of formula (I) are suitable compounds for treating and / or preventing RNA viral infections caused by group V RNA viruses, more particularly pneumovirus infections, most particularly RSV viral infections.

[0242] Example 10: Dengue 2 virus The compounds according to the invention have been the subject of pharmacological tests which have demonstrated their relevance as active substances in therapy, in particular for preventing, inhibiting or treating dengue 2 virus infection.

[0243] Materials and Methods A Protocol for Screening Antiviral Compounds for DENV-2 Inhibition and Cytotoxicity Using the Viral ToxGlo Assay A549 cells were maintained in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum, 100 U / ml penicillin, and 100 μg / ml streptomycin. For the screening assay, they were grown to 90% confluency, trypsinized, and harvested. Trypsin was neutralized in cell culture medium and cells were centrifuged at 150 x g for 5 min, the supernatant was discarded, and the cell pellet was resuspended in assay medium (DMEM supplemented with 2% fetal bovine serum, 100 U / ml penicillin, and 100 μg / ml streptomycin). Cells were plated at 1.0x10 in 50 μl in 96-well white clear-bottom cell culture plates. 4 Cells were seeded at a density of 1000 cells / well. Only medium / background control column assay medium was added. The cell plates were placed in a humidified chamber and incubated overnight at 37°C / 5% CO2. After overnight incubation, cells were checked for confluency and healthy appearance.

[0244] Test compounds were prepared at a final concentration of 10 μM with a maximum DMSO concentration of 1% (maximum final assay concentration of DMSO of 0.1%) and added to the cell plates in a volume of 10 μl. For cell control and virus control wells, only the test article solvent was added. As a positive inhibition control, 7-deaza-2'-C-methyladenosine was added at 100 μM to three wells. Virus (DENV-2 strain 16681) or assay medium for cytotoxicity test wells and medium / cell control wells were added immediately after the test article at an MOI of 0.5 and 40, respectively, for the 96-well plate. Virus suspensions were prepared by thawing DENV-2 frozen stocks and diluting to the required concentration of plaque forming units with assay medium.

[0245] The cell plates were further incubated at 37°C / 5% CO2 in a humidified chamber for 5 days pi. After the incubation period, the cells were observed under a microscope to check for characteristic cytopathic effects in virus control wells and healthy cells in cell control wells. After the plates were adjusted to room temperature, 20 μl of Viral ToxGlo (Promega) was added to each well of the 96-well cell plate. After the plates were incubated at room temperature for 5 minutes, luminescence was measured with a spectrophotometer (Envision, PerkinElmer).

[0246] DENV-2 inhibition was calculated as the percentage of cytopathic effect inhibition relative to virus control, and cytotoxicity was calculated as the percentage of cell viability relative to cell control wells.

[0247] [Table 6]

[0248] conclusion Based on the above results, it can be concluded that the compounds of formula (I) are suitable compounds for treating and / or preventing RNA viral infections caused by group IV RNA viruses, more particularly flavivirus infections, most particularly dengue 2 virus infections.

[0249] The present invention further relates to a pharmaceutical composition comprising at least one of the novel compounds defined above, or any one of their pharma- ceutically acceptable salts, or at least one of the compounds (2) to (26) and (28) to (79) defined above or in claim 3, more preferably any one of the compounds 2 to 8, 10, 12 to 14, 16, 17, 20 to 23, 28, 29, 31, 32, and 38 to 57, 63, 76 and 77, or a pharma- ceutically acceptable salt thereof, and also at least one pharma- ceutically acceptable excipient.

[0250] The pharmaceutical compositions of the present invention may contain one or more compounds of the present invention in any of the forms described herein.

[0251] A still further object of the present invention is at least one compound of formula (I) as defined above, compounds (1) to (79) as defined above, more preferably any one of compounds 2 to 8, 10, 12 to 14, 16, 17, 20 to 23, 28, 29, 31, 32 and 38 to 57, 63, 76 and 77, or a pharma- ceutically acceptable salt thereof, according to the present invention for the preparation of a medicament for the treatment and / or prevention in a patient of an RNA virus infection, most preferably an RNA virus infection caused by an RNA virus from group IV or V according to the Baltimore classification, such as a chikungunya infection, a dengue infection, an influenza infection or an RSV infection.

[0252] The present invention therefore relates to one of the compounds of formula (I) as defined above, and to any one of the compounds (1) to (79), more preferably compounds 1 to 8, 10, 12 to 14, 16, 17, 20 to 23, 28, 29, 31, 32 and 38 to 57, 63, 76 and 77, or a pharma- ceutically acceptable salt thereof, as an agent for inhibiting, preventing or treating an RNA virus infection, more preferably an RNA virus infection from group IV or V, such as a chikungunya infection, a dengue infection, an influenza infection or an RSV infection.

[0253] According to certain embodiments, the treatment is continuous or discontinuous.

[0254] "Continuous treatment" refers to long-term treatment which can be performed at various dosing frequencies, for example, once a day, every third day, once a week or once every two weeks, or once a month.

[0255] In one embodiment, the compound of formula (I), or any one of its pharma- ceutically acceptable salts, is administered at a dose ranging from 0.1 to 1000 mg, in particular from 0.1 to 10 mg, or at a dose varying, for example, from 10 to 200 mg, for example from 200 to 1000 mg.

[0256] Another object of the present invention is to treat an RNA virus infection, more preferably an RNA virus infection from group IV or V, even more preferably a chikungunya infection, a dengue infection, an influenza infection or an RSV infection, even more preferably an RSV virus infection, The present invention relates to a therapeutic method for treating and / or preventing an RNA virus infection in a patient caused by an RNA virus belonging to group IV or group V of the Baltimore classification, which comprises administering a therapeutically effective amount of a compound of formula (I) or of compounds (1) to (79) as defined above, or an acceptable salt thereof.

[0257] In a particular embodiment, the present invention provides the use of a compound of formula (I) according to the invention, or any one of its pharma- ceutically acceptable salts, or a pharma- ceutically active derivatives thereof, or a method according to the invention, wherein the compound of formula (I) is to be administered in combination with an auxiliary agent useful in the treatment of said RNA virus infection, more preferably an RNA virus infection from said group IV or V, such as a chikungunya infection, a dengue infection, an influenza infection or an RSV infection, in particular an RSV infection.

[0258] The compounds can be administered via any mode of administration, such as intramuscular, intravenous, intranasal or oral routes.

[0259] The compounds of the present invention may be administered as prodrugs, e.g., esters, of the compounds involved in the present invention, where appropriate. "Prodrug" means a compound that is convertible in vivo to a compound of the present invention by metabolic means (e.g., by hydrolysis, reduction, or oxidation). For example, an ester prodrug of a compound of the present invention may be convertible to the parent molecule by hydrolysis in vivo. Suitable esters of the compounds of the present invention are, for example, acetate, citrate, lactate, tartrate, malonate, oxalate, salicylate, propionate, succinate, fumarate, maleate, methylene-bis-β-hydroxynaphthate, gentisate, isethionate, di-p-toluoyltartrate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, cyclohexylsulfonate, and quinate. Examples of ester prodrugs are those described by FJ Leinweber, Drug Metab. Res., 1987, 18, 379. As used herein, reference to the compounds of the invention is meant to also encompass any prodrug or metabolite forms.

[0260] The composition of the present invention may further comprise one or more additives, such as diluents, excipients, stabilizers and preservatives. Such additives are well known to those skilled in the art and are described in particular in Ullmann's Encyclopedia of Industrial Chemistry, Vol. 6, No. 6, pp. 111-115, 2002. th Ed. (various editors, 1989-1998, Marcel Dekker) and "Pharmaceutical Dosage Forms and Drug Delivery Systems" (ANSEL et al., 1994, WILLIAMS & WILKINS).

[0261] The above additives are selected according to the dosage form and the desired mode of administration.

[0262] The compositions of the present invention can be administered in any manner, including but not limited to oral, parenteral, sublingual, transdermal, vaginal, rectal, transmucosal, topical, intranasal, buccal or intranasal administration by inhalation, or combinations thereof. Parenteral administration includes but is not limited to intravenous, intraarterial, intraperitoneal, subcutaneous, intramuscular, intrathecal, and intraarticular. The compositions of the present invention can also be administered in the form of an implant, which allows for slow release of the composition and slow controlled intravenous (iv) infusion.

[0263] For example, the compounds of formula (I) can be present, in association with suitable excipients, in any pharmaceutical form suitable for enteral or parenteral administration, for example in the form of plain or coated tablets, hard gelatin, soft shell capsules and other capsules, suppositories, or drinks, e.g. suspensions, syrups, or injectable solutions or suspensions, in doses allowing the daily administration of 0.1 to 1000 mg of active substance.

[0264] In a particular embodiment, the compounds of formula (I) according to the present invention are administered orally.

[0265] The oral administration route is particularly preferred in the prophylactic or therapeutic aspects of the present invention.

[0266] According to other embodiments, the pharma- ceutically acceptable compositions of the present invention may be administered to humans and other animals orally, rectally, parenterally, intracisternally, intravaginally, intraperitoneally, topically (as powders, ointments, or drops), bucally, as an oral or nasal spray, or the like, depending on the severity of the infection being treated.

[0267] The compositions of the present invention may be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, bucally, intravaginally, or via an implanted reservoir. As used herein, the term "parenteral" includes subcutaneous, intravenous, intramuscular, intra-articular, intrasynovial, intrasternal, intrathecal, intrahepatic, intralesional, and intracranial injection or infusion techniques. Preferably, the compositions are administered orally, intraperitoneally, or intravenously. Sterile injectable forms of the compositions of the present invention may be aqueous or oily suspensions. These suspensions may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Vehicles and solvents that may be used are water, Ringer's solution, and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium.

Claims

1. Any one of the compounds of formula (I) below, or a pharma- ceutically acceptable salt thereof: 【Chemistry 1】 Where: m is 0, 1 or 2; R 1 teeth, (i) CF 3 base, (ii) (C 1 ~C 10 ) alkyl group, wherein the (C 1 ~C 10 ) one of the carbon atoms of the alkyl group may be replaced by an oxygen atom, and 1 ~C 10 ) The alkyl group is -CF 3 groups, halogen atoms, pyridyl groups, phenyl groups, (C 3 ~C 6 ) cycloalkyl group, (C 3 ~C 6 ) optionally substituted with one or more heterocycloalkyl or hydroxy groups; (iii) (C 3 ~C 6 ) cycloalkyl group or (C 3 ~C 6 ) heterocycloalkyl groups, where these groups are (C 1 ~C 2 ) may be substituted by one or two groups independently selected from an alkyl group or a fluorine atom, or (iv) a phenyl or naphthyl group, wherein the group is (C 1 ~C 4 ) alkyl group, halogen atom, -COOR' group, (C 1 ~C 5 ) alkoxy group, -SO 2 -NR a R b Group, -SO 3 H group, -OH group, -O-SO 2 -OR c Group or -OP(=O)-(OR c )(OR d ) groups, represents R 3 represents a chlorine atom or a hydrogen atom, R is (C 1 ~C 4 ) alkyl group, (C 3 ~C 6 ) cycloalkyl group, halogen atom, (C 1 ~C 5 ) alkoxy group, -SO 2 -NR a R b Group, -SO 3 H group, -OH group, -O-SO 2 -OR c Group, or -OP(=O)-(OR c )(OR d ) group, the OR 1 group is in the para or meta position on the phenyl relative to the -NH- group; R', R a and R b independently represent a hydrogen atom, a (C 1 -C 5 ) alkyl group or a (C 3 -C 6 ) cycloalkyl group; R c and R d independently represent a hydrogen atom, Li, Na, K, N(R a ) 4 or a benzyl group; and R 2 However, (C 3 ~C 6 ) cycloalkyl group or (C 3 ~C 6 ) heterocycloalkyl groups, where these groups are 1 ~C 2 ) may be substituted by one or two groups independently selected from an alkyl group or a fluorine atom.

2. R 1 but, (i) CF 3 base, (ii) (C 1 ~C 10 ) alkyl group, wherein the (C 1 ~C 10 One of the carbon atoms of the alkyl group may be replaced by an oxygen atom, and 1 ~C 10 ) The alkyl group is -CF 3 groups, halogen atoms, pyridyl groups, phenyl groups, (C 3 ~C 6 ) cycloalkyl group or (C 3 ~C 6 ) may be substituted with one or more heterocycloalkyl or hydroxy groups; or (iii) (C 3 ~C 6 ) cycloalkyl group or (C 3 ~C 6 ) heterocycloalkyl groups, where these groups are 1 ~C 2 ) optionally substituted by one or two alkyl groups or fluorine atoms; 2. The compound of claim 1, wherein:

3. Any one of the compounds of formula (I) below, or a pharma- ceutically acceptable salt thereof: 【Chemistry 2】 Where: m is 0, 1 or 2; R is (C 1 ~C 4 ) alkyl group, (C 3 ~C 6 ) cycloalkyl group, halogen atom, (C 1 ~C 5 ) alkoxy group, -SO 2 -NR a R b Group, -SO 3 H group, -OH group, -O-SO 2 -OR c Group, or -OP(=O)-(OR c )(OR d ) group, the OR 1 group is in the para or meta position on the phenyl relative to the -NH- group; R a and R b independently represent a hydrogen atom, a (C 1 -C 5 ) alkyl group, or a (C 3 -C 6 ) cycloalkyl group; R c and R d each independently represent a hydrogen atom, Li, Na, K, N(R a ) 4 or a benzyl group; R 2 is (C 1 ~C 10 ) alkyl group, (C 3 ~C 6 ) cycloalkyl group or (C 3 ~C 6 ) heterocycloalkyl group, 3 ~C 6 ) cycloalkyl group or (C 3 ~C 6 ) Heterocycloalkyl groups are (C 1 ~C 2 ) optionally substituted with one or two groups independently selected from an alkyl group or a fluorine atom; R 3 represents a chlorine atom or a hydrogen atom, and R 1 but, (I C 1 ~C 10 ) alkyl group, wherein the (C 1 ~C 10 one of the carbon atoms of the (C 1 -C 10 ) alkyl group may be replaced by an oxygen atom, the (C 1 -C 10 ) alkyl group is substituted by one or more groups which are independently a (C 3 -C 6 ) cycloalkyl group or a (C 3 -C 6 ) heterocycloalkyl group, and the (C 1 ~C 10 ) The alkyl group is -CF 3 may be further substituted by one or more of a group, a halogen atom, a pyridyl group, a phenyl group, or a hydroxy group; or (ii) (C 3 ~C 6 ) cycloalkyl group or (C 3 ~C 6 ) heterocycloalkyl groups, where these groups are 1 ~C 2 ) optionally substituted with one or two alkyl groups or fluorine atoms; Represents.

4. Any one of the compounds of formula (I) below, or a pharma- ceutically acceptable salt thereof: 【Chemistry 3】 Where: m is 0, 1 or 2; R 2 is a hydrogen atom, (C 1 ~C 10 ) alkyl group, (C 3 ~C 6 ) cycloalkyl group or (C 3 ~C 6 ) heterocycloalkyl group, 3 ~C 6 ) cycloalkyl group or (C 3 ~C 6 ) Heterocycloalkyl groups are (C 1 ~C 2 ) optionally substituted with one or two groups independently selected from an alkyl group or a fluorine atom; R 3 represents a chlorine atom or a hydrogen atom, R', R a and R b are independently a hydrogen atom, (C 1 ~C 5 ) alkyl group or (C 3 ~C 6 ) represents a cycloalkyl group; R c and R d are independently hydrogen atoms, Li, Na, K, N(R a ) 4 or a benzyl group, R is (C 1 ~C 4 ) alkyl group, (C 3 ~C 6 ) cycloalkyl group, halogen atom, (C 1 ~C 5 ) alkoxy group, -SO 2 -NR a R b Group, -SO 3 H group, -OH group, -O-SO 2 -OR c Group, or -OP(=O)-(OR c )(OR d ) group, and R 1 is (C 1 ~C 4 ) alkyl group, halogen atom, -COOR' group, (C 1 ~C 5 ) alkoxy group, -SO 2 -NR a R b Group, -SO 3 H group, -OH group, -O-SO 2 -OR c Group, or -OP(=O)-(OR c )(OR d ) groups, or (C 1 ~C 4 ) alkyl group, halogen atom, -COOR' group, (C 1 ~C 5 ) alkoxy group, -SO 2 -NR a R b Group, -SO 3 H group, -OH group, -O-SO 2 -OR c Group or -OP(=O)-(OR c )(OR d ) groups, The OR 1 group is in the para or meta position on the phenyl relative to the -NH- group.

5. A compound selected from the table below, or a pharma- ceutically acceptable salt thereof, such as the hydrobromide, tartrate, citrate, trifluoroacetate, ascorbate, hydrochloride, tosylate, triflate, maleate, mesylate, formate, acetate and fumarate salts. 【Table 1】 。

6. An agent for use in the treatment and / or prevention of an RNA viral infection caused by an RNA virus belonging to Group IV or Group V of the Baltimore Classification, comprising any one of the compounds of formula (I) according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, or any one of the compounds (2) to (26) and (28) to (79) defined in claim 5, or a pharmaceutically acceptable salt thereof, wherein the RNA viral infection caused by an RNA virus belonging to Group IV or Group V of the Baltimore Classification is selected from RSV viral infection, chikungunya viral infection, dengue viral infection and influenza viral infection.

7. A pharmaceutical composition for use in the treatment and / or prevention of an RNA viral infection caused by an RNA virus belonging to Group IV or Group V of the Baltimore Classification, comprising at least one compound according to any one of claims 1 to 4, or any one of its pharmaceutical acceptable salts, or at least one of compounds (2) to (26) and (28) to (79) as defined in claim 5, or any one of their pharmaceutical acceptable salts, and also at least one pharmaceutical acceptable excipient, wherein the RNA viral infection caused by an RNA virus belonging to Group IV or Group V of the Baltimore Classification is selected from RSV viral infection, chikungunya virus infection, dengue virus infection and influenza virus infection.

8. A synthetic process for preparing a compound of formula (I) according to any one of claims 1 to 5, comprising the steps of: A compound of formula (II) 【Chemistry 4】 with a compound of formula (III) 【Chemistry 5】 in the presence of an inorganic base and a diphosphine and in the presence of an organometallic catalyst to obtain a compound of formula (I), Here, R 1 , R 2 , R 3 , R and m are as defined in any one of claims 1 to 5. The method.

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