Novel PD-l1 inhibitors

Abstract

The present invention relates to compounds for modulating PD-1 / PD-L1 protein / protein interaction that are useful in the treatment of various diseases associated with over-expression of PD-1 / PD-L1, including infectious diseases and cancer. The invention additionally relates to compositions comprising such compounds as well as to their uses.

Description

[0001] NOVEL PD-L1 INHIBITORS Technical field The present invention relates to compounds for modulating PD-1 / PD-L1 protein / protein interaction that are useful in the treatment of various diseases associated with over-expression of PD-1 / PD-L1, including infectious diseases and cancer. The invention additionally relates to compositions comprising such compounds as well as to their uses. Background art Immune checkpoint molecules are inhibitory receptors expressed on immune cells that trigger immunosuppressive signalling pathways. These molecules are crucial for maintaining self- tolerance and for modulating the length and magnitude of effector immune responses in peripheral tissues, in order to minimize collateral tissue damage. The protein-protein interaction PD1 / PD-L1 is an important immune checkpoint. PD-1 is expressed on all activated T cells and acts as an inhibitory brake to tamper T cell immune responses as an immune tolerance mechanism. PD-1 inhibits T cell function when bound to either of its binding partners, PD-L1 or PD-L2(1). PD-L1 has been found to be overexpressed in various types of cancer cells. The up-regulation of PD-1 on immune cells also occur during acute and chronic infections, viral as well as bacterial or fungal. Accordingly, this immune checkpoint is believed to play a critical role in the suppression of antigen-specific T cell response in diseases like cancer and infections. Targeting the programmed cell death protein 1 / programmed cell death 1 ligand 1 (PD-1 / PDL1) interaction has become an established strategy for cancer immunotherapy. Additionally, the fact that these inhibitory pathways are also exploited for immune evasion by pathogens suggests that blockade could be used for the prevention and treatment of infectious diseases,in either the acute or chronic phases of infection (2)(3).The majority of clinically used PD-1 / PD-L1 inhibitors are monoclonal antibodies but their applications are limited due to their PD-1 / PD-L1 inhibitors. However, the development of small molecule immunomodulators of the pathway has lagged far behind, and at present, only a limited number of drug candidates show good PD-1 / PD-L1blocking activity in cell-based assays (2). Therefore, the identification of chemical moieties,especially small molecule inhibitors, that facilitate this inhibition is necessary. In particular, it would be useful to have compounds for oral administration that could help overcoming the limitations of antibodies. Accordingly, the identification and development of new PD-1 / PD-L1 inhibitor compounds for treating diseases or conditions associated with reversion of T cell exhaustion would open new opportunities in the realm of cancer and infections treatment. Non-patent literature (1) M.N. Wikes, S. R. Lewin, Nat Rev Immunol. 2018, Vol. 18(2), 91–104(2) C. Fang-Fang, L. Zheng et al. Oncoimmunology, 2020, Vol. 9 no. 1(3) L. Chang, N.P. Seeram et al. Cancer Cell Int. 2021, 21-239Summary of the invention The present invention provides a compound of Formula (I) or a pharmaceutically acceptable salt or a stereoisomer thereof wherein the substituents are as defined herewith. The present invention also relates to a pharmaceutical composition comprising a compound of the invention, or a pharmaceutically acceptable salt or a stereoisomer thereof, and one or more pharmaceutically acceptable carrier or excipient. The present invention also relates to a pharmaceutical composition comprising a compound of the invention, specifically the compound of Formula (I), or a pharmaceutically acceptable salt or a stereoisomer thereof, and one or more pharmaceutically acceptable carrier or excipient. The present invention further provides compounds and compositions for use in a method of treatment of diseases or disorders associated with the reversion of T cell exhaustion, wherein such disease can be cancer or an infection. The present invention further provides a compound of Formula (I) and a composition comprising a compound of Formula (I) for use in a method of treatment of diseases or disorders associated with the reversion of T cell exhaustion, wherein such disease can be cancer or an infection. The present invention additionally provides methods of treatment of diseases or disorders associated with the reversion of T cell exhaustion, wherein such disease can be cancer or an infection. In particular, the present invention additionally provides methods of treatment of diseases or disorders associated with the reversion of T cell exhaustion, wherein such disease can be cancer or an infection, and wherein the method comprises a step of administering the compound of Formula (I) or compositions comprising the compound of Formula (I). The present invention moreover provides a use of the compound of Formula (I) for the manufacture of a medicament. The present invention relates to compounds of Formula (I), and in particular to related compounds of Formulae (II) and (III), which represent specific embodiments within the general Formula (I). Accordingly, the compositions, uses, and methods described herein with respect to compounds of Formula (I) also apply to compounds of formulae (II) and (III). Detailed description of the invention Definitions Unless otherwise specified, all scientific, chemical names, and technical terms used herein have the same meaning as commonly understood by the skilled person. A dash (–) at the front or end of a chemical group is a matter of convenience to indicate the point of attachment. However, chemical groups may be depicted with or without one or more dashes without losing their ordinary meaning. If not otherwise specified, each linking substituent include both the forward and backward forms of the linking substituent. For example, -C6-10aryl-C1-4alkyl- includes both -C6-10 aryl-C1-4 alkyl- and -C1-4 alkyl-C6-10 aryl- and is intended to disclose each of the forms individually and can be attached on one side only (e.g., C1-4 alkyl or C6-10 aryl-) or on both sides. The term "substituted" means that an atom or group of atoms formally replaces hydrogen as a "substituent" attached to another group. The phrase "optionally substituted" means unsubstituted or substituted. The term "substituted", unless otherwise indicated, refers to any level of substitution, e.g., mono-, di-, tri-, or tetra- or penta-substitution, where such substitution is permitted. The substituents are independently selected, and substitution may be at any chemically accessible position. It is to be understood that substitution at a given atom is limited by valency, and by molecular stability. In the present disclosure letters as Xn, Yn, Rncan be used to indicate the substitution of a hydrogen atom with one or more substituents (e.g., Ra, Rb, Rc, Rd, Re, Rf). The substituents are each independently selected, for example, if one Rn is selected to be a certain atom or group of atoms (e.g., C1-6 alkyl), the other Rns can be anything else from the lists of possible substituents. The term "alkyl," as used herein refers to a saturated hydrocarbon group of general formula - CnH2n+1that may be straight-chained or branched. Non limiting examples of alkyl moieties include methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl etc. The term "Cn-malkyl" as used herein refers to an alkyl group having n to m carbon atoms. For example, the term "C1-6alkyl" is intended to individually disclose (without limitation) methyl, ethyl, C3alkyl, C4alkyl, C5alkyl and C6alkyl. The term "alkynyl," as used herein refers to a straight-chain or branched hydrocarbon group corresponding to an alkyl group having one or more triple carbon-carbon bonds. The term "Cn- m alkynyl" refers to an alkynyl group having n to m carbons. Non limiting examples of alkynyl groups include ethynyl, propyn-1-yl, propyn-2-yl and the like. The term "alkoxy," (AlkO) as used herein refers to a group of formula -O-alkyl, wherein the alkyl group is as defined above. The term "Cn-m alkoxy" refers to an alkoxy group, the alkyl group of which has n to m carbons. Non limiting examples of alkoxy groups include methoxy (MeO), ethoxy (OEt), propoxy (e.g., n-propoxy and isopropoxy (PriO)) and the like. The terms "halogen" or “halo” as used herein refers to halogen atom selected from fluoro (F), chloro (Cl), or bromo (Br). In some preferred embodiments of the present invention halogen groups are Cl. The term nitrile" or "cyano" as used herein refers to a group of formula -CN, also written as (- C≡N). The term "amino," as used herein refers to a group of formula -NH2. The term Cn-CmAlkyl-NHRnrefers to an amino group linked to an alkyl group defined as above, wherein additionally one hydrogen atom is substituted with an atom or a group of atoms. The term "carbamyl," as used herein refers to a group of formula -C(O)NH2, -NH2C(O),NHC(O)Rn, C(O)NHRn, also written NHCORn, CONHRn.The term "carbonyl," as used herein refers to a -C(=O)- group, which also may be written as -C(O)-, or -CO-. The term "oxo"(=O) refers to an oxygen atom as a divalent substituent, forming a carbonyl group when attached to carbon, or attached to a heteroatom forming a sulfoxide or sulfone group, or an N-oxide group. In some embodiments, aryl or heterocyclic groups may be optionally substituted by 1 or 2 oxo (=O) substituents. The term "aryl," as used herein refers to an aromatic hydrocarbon group, which may be monocyclic or polycyclic (e.g., having 2 fused rings). The term "Cn-m aryl" refers to an aryl group having from n to m ring carbon atoms. Aryl groups include, e.g., phenyl, naphthyl, indanyl, indenyl and the like. The term "heteroaryl" as used herein refers to a monocyclic or polycyclic aromatic heterocycle having at least one heteroatom ring member selected from sulfur, oxygen and nitrogen. For example, the term 5-14 membered heteroaryl refers to an aromatic heterocycle having 5-14 ring atoms including carbon atoms and 1, 2, 3 or 4 heteroatom ring members independently selected from nitrogen, sulfur and oxygen, preferably nitrogen. Non-limiting examples of heteroaryl groups include pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrazolyl, azolyl, imidazolyl, furanyl, quinolinyl, isoquinolinyl, naphthyridinyl, indolyl, benzofuranyl, and the like. It will be understood that the heteroaryl groups depicted herein are aromatic systems with delocalized π-electrons. The double bonds are shown in fixed positions for simplicity; however, it will be understood that the actual bonding is delocalized within the aromatic system. The term "cycloalkyl," as used herein refers to a non-aromatic hydrocarbon ring system (monocyclic, bicyclic or polycyclic), including cyclized alkyl and alkenyl groups. The term "Cn-m cycloalkyl" refers to a cycloalkyl that has n to m ring member carbon atoms. Cycloalkyl groups can include mono- or polycyclic (e.g., having 2, 3 or 4 fused rings) groups. Non limiting examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptatrienyl, and the like. The term "heterocycloalkyl," as used herein refers to a non-aromatic ring or ring system, which may optionally contain one or more alkenylene groups as part of the ring structure, which has at least one heteroatom ring member independently selected from nitrogen, sulfur and oxygen, and which can have for example, 4-14 ring members, 4-10 ring members, 4-7 ring members, or 4-6 ring members. Included within the term "heterocycloalkyl" are monocyclic 4-, 5-, 6- and 7-membered heterocycloalkyl groups. Non limiting examples of monocyclic heterocycloalkyl groups include piperidinyl, piperazinyl, pyrrolidinyl, azetidinyl, tetrahydropyranyl, tetrahydrofuranyl, and the like. Heterocycloalkyl groups can include also bicyclic or polycyclic (e.g., having two or three fused or bridged attached rings) or spirocyclic ring systems.For example, are to be considered as heterocycloalkyl substituted with anoxo group (=O) and with an R group respectively. The term “cyclic-amide” as used herein refers to cyclic compound with the amide group – C(=O)N– in the ring. Cn-Cm-cyclic-amide refers to a cyclic-amide that has n to m ring member carbon atoms (e.g., C3-C6). The terms described above, can be used alone or in combination with each other. For example, the terms C6-10aryl-C1-4alkyl-, 5-14 membered heteroary-C1-4alkyl-, C1-6alkyl-NHRa, or Cn-Cm- cyclic-amide-C1-4alkyl- refer to an aryl, a 5-14 membered heteroaryl, an amino group or a Cn-Cm-cyclic-amide combined with an alkyl group as defined above. For example, , orare to be considered within the above definition of C6-10 aryl-C1-4 alkyl-, and Cn-Cm- cyclic-amide-C1-4alkyl-. The term "pharmaceutically acceptable" herewith is intended to those compounds and materials, which are generally safe, non-toxic, and neither biologically nor otherwise undesirable and includes that which is acceptable for veterinary use as well as human pharmaceutical use. The terms "subject" or "patient," or “recipient” used interchangeably, refer to any mammal, preferably mice, rats, other rodents, rabbits, dogs, cats, swine, or primates, and most preferably humans. The phrase "therapeutically effective amount" refers to the amount of active compound or pharmaceutical agent that elicits the biological or medicinal response in a tissue, system, animal, individual or human. As used herein, the term "treating" or "treatment" refers to the inhibition of the disease; condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder; and / or to ameliorating the disease; e.g., ameliorating a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., reversing the pathology and / or symptomatology) such as decreasing the severity of disease. Compounds The present invention relates to a compound of Formula (I) or a pharmaceutically acceptable salt or a stereoisomer thereof: Formula I wherein: X1-X4are each independently C or N, with the proviso that at least three of X1-X4are N; Y1-Y3are each independently C or N; with the proviso that at least one of them is N; p is 1-3; q is 1-3; R3and R5are each independently methyl, Cl, or CN; R4is H, C1-6alkyl, halogen, or CN; R6 is H, C1-6 alkyl, halogen, or CN; R7is C1-4alkoxy; Raais H or C1-6alkyl, or Rccand Rcare linked together to form a 4-10 membered heterocycloalkyl optionally substituted with 1, or 2 independently selected Rd substituents; Ra is selected from C1-6 alkyl, C1-6 alkoxy, and C3-10 cycloalkyl, or Raa and Ra are linked together to form a 4-10 membered heterocycloalkyl optionally substituted with 1, or 2 independently selected Rdsubstituents; and wherein the C1-6alkyl, C1-6alkoxy, and C3-10cycloalkyl of Raare each independently substituted with 1, or 2 independently selected Rdsubstituents; Rcc is H or C1-6 alkyl, or Rcc and Rc are linked together to form a 4-10 membered heterocycloalkyl optionally substituted with 1, or 2 independently selected Rd substituents; Rcis selected from C1-6alkyl, C1-6alkoxy, and C3-10cycloalkyl, or Rccand Rcare linked together to form a 4-10 membered heterocycloalkyl optionally substituted with 1, or 2 independently selected Rd substituents; and wherein the C1-6 alkyl, C1-6 alkoxy, and C3-10 cycloalkyl of Rc are each independently substituted with 1, or 2 independently selected Rd substituents; each Rd is independently selected from C1-6 alkyl, C1-6 alkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C3-C6cyclic amide, CN, NH2, C(O)ORe, NHRe, NReRe, NReC(O)Re, NReC(O)ORe, ORe, (=O), S(O)2Reand S(O)2NReRe, and wherein the C1- 6 alkyl, C1-6 alkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, and C3-C6cyclic amide of Rdare each optionally substituted with 1, 2, or 3 independently selected Rf substituents; each Reis independently selected from H, OH, COOH, C(O)Rf, C1-6alkyl, and 5-14 membered heteroaryl, wherein the C1-6alkyl, and 5-14 membered heteroaryl of Reare each optionally substituted with 1, 2 or 3 independently selected Rfsubstituents; each Rf is independently selected from H, C1-4 alkyl, halogen, CN, COOH, OH, and (=O). In the compound of Formula (I) described above, preferably, X1-X4 are each independently C or N, with the proviso that three of X1-X4 are N; the subscript p is 1; the subscript q is 1; R7 is methoxy (MeO), ethoxy (EtO) or isopropoxy (PriO); Y2 and Y3 are each C and Y1 is N; R3and R5are each independently methyl, or Cl; R4and R6are H; Raa is H or C1-6 alkyl; Rais selected from C1-6alkyl and C3-10cycloalkyl; and wherein the C1-6alkyl and C3-10cycloalkyl are each independently substituted with 1 Rdsubstituent; Rcc is H or C1-6 alkyl; Rc is selected from C1-6 alkyl and C3-10 cycloalkyl; and wherein the C1-6 alkyl and C3-10 cycloalkyl are each independently substituted with 1 Rd substituent; each Rdis independently selected from C1-6alkyl, C1-6alkoxy, and C3-C6cyclic amide, C(O)ORe, NHRe, NReC(O)Re, ORe, and wherein the C1-6 alkyl, C1-6 alkoxy, C3-C6 cyclic amide of Rd are each optionally substituted with 1, or 2 independently selected Rf substituents; each Re is independently selected from H, OH, COOH, and C(O)Rf; each Rfis independently selected from H, C1-4alkyl, halogen, CN, COOH, OH, and (=O). Preferably, Rfis independently selected from H, methyl, C2-4alkyl, COOH, OH, and (=O) As mentioned above, it will be understood that the heteroaryl groups depicted herein are aromatic systems with delocalized π-electrons. The double bonds are shown in fixed positions for simplicity; however, it will be understood that the actual bonding is delocalized within the aromatic system. In particular, in the present context, , .In the compound of Formula (I) described above, the heteroaryl group be selected from the group consisting of: the subscript p=1, Raaand Raare as defined in any embodiment disclosed herein.Preferably, the heteroaryl In the compound of Formula (I) described above, NRccRccan be selected from the group consisting of: the other variables other variables of Formula (I) are as defined in any embodiment disclosed herein. In the compound of Formula (I) described above, Raacan be H and Racan be selected from: the other variables other variables of Formula (I) are as defined in any embodiment disclosed herein. In the compound of Formula (I) described above, preferably, the heteroaryl group In the compound of Formula (I) described above, preferably R3and R5are both Cl; preferably, R3 and R5 are both methyl. In the compound of Formula (I) described above, preferably R7 is MeO. In the compound of Formula (I) described above, preferably R3and R5are both Cl; preferably, R3and R5are both methyl, Y2and Y3are C, Y1is N, and R7is MeO. In some embodiments, in the compound of Formula (I) described above, Y2and Y3are C, Y1is N, R7is MeO, R3and R5are Cl; R4, and R6are H, q is 1, p is 1, Rccis H, Rcis C1-6alkyl substituted with Rd, wherein Rdis ORe, and Reis H, Raais H, Rais C1-6alkyl substituted with Rd, wherein Rdis ORe, and and Re is H. In some embodiments, in the compound of Formula (I) described above, Y2 and Y3 are C, Y1 is N, R7 is isopropoxy, R3 and R5 are Cl; R4, and R6 are H, q is 1, p is 1, Rcc is H, Rc is C1-6 alkyl substituted with Rd, wherein Rdis ORe, and Reis H, Raais H, Rais C1-6alkyl substituted with Rd, wherein Rdis ORe, and and Reis H. In some embodiments, in the compound of Formula (I) described above, Y2 and Y3 are C, Y1 is N, R7 is MeO, R3 and R5 are both methyl, X1-X4 are each independently C or N, with the proviso that three of X1-X4 are N; the subscript p is 1; the subscript q is 1, R4 and R6 are H; the other variables of Formula (I) are as defined in any embodiment disclosed herein. In some embodiments, provided herewith is a compound of Formula (I), Y2 and Y3 are C, Y1 is N, R7 is MeO, R3 and R5 are Cl; R4, and R6 are H, q is 1, p is 1, Rcc is H, Rc is C1-6 alkyl substituted with Rd, wherein Rd is NHRe, and Re is C(O)Rf, Rf is C1-4 alkyl, Raa is H, Ra is C1-6 alkyl substituted with Rd, wherein Rd is NHRe, and Re is C(O)Rf, Rf is C1-4 alkyl. In some embodiments, in the compound of Formula (I) described above, Y2and Y3are C, Y1is N, R7is OEt, R3and R5are Cl; R4, and R6are H, q is 1, p is 1, Rccis H, Rcis C1-6alkyl substituted with Rd, wherein Rdis ORe, and Reis H, Raais H, Rais C1-6alkyl substituted with Rd, wherein Rdis ORe, and and Re is H. In each of the above-described embodiments, independently, C1-6 alkyl is preferably, methyl, ethyl, or C3alkyl. In some embodiments, provided herewith is a compound of Formula (I) wherein R3and R5are Cl; R4 and R6 are H, q is 1, p is 1, R7 is MeO, Y2 and Y3 are C, Y1 is N, the heteroaryl group Raa is H and Ra is selected from:

[0002] NRccRc is selected from: Preferably, the compounds of the invention are symmetric compounds, in which Raaand Rccare both H and Ra and Rc are the same. In some embodiments, provided herewith is a compound of Formula (I) wherein R3 and R5 are Cl; R4 and R6 are H, q is 1, p is 1, R7 is MeO, Y2 and Y3 are C, Y1 is N, the heteroaryl group Raa is H and Ra is selected from: NRccRcis selected from: Preferably, the compounds of the invention are symmetric compounds, in which Raa and Rcc are both H and Ra and Rc are the same.In the compound of Formula (I) described above, the heteroaryl group be selected from the group consisting of: the subscript p=1, Raa and Ra are as defined in any embodiment disclosed herein. In some embodiments, provided herein, is a compound having Formula (II). Compound of Formula (II) of the present invention is a preferred embodiment of the compound of Formula (I) or a pharmaceutically acceptable salt or a stereoisomer thereof described above, and is specifically a compound or a pharmaceutically acceptable salt or a stereoisomer thereof represented by the following formula (II): or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein the subscript q is 1, the subscript p is 1, wherein Y1is N,and wherein X1-X4,Rc, Rcc, Raa, Ra, R3, R4, R5, R6and R7have the same meaning as in any embodiment of Formula (I) described herein. In other words, Formula (I) can be replaced with Formula (II) in any of the above described embodiments, as the skilled person will readily understand. In some embodiments, provided herein, is a compound having Formula (III). Compound of Formula (III) of the present invention is a preferred embodiment of the compound of Formula (I) or a pharmaceutically acceptable salt or a stereoisomer thereof described above, and is specifically a compound or a pharmaceutically acceptable salt or a stereoisomer thereof represented by the following formula (III): or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein the subscript q is 1, the subscript p is 1, wherein Y1is N,and wherein X1-X4,Rc, Rcc, Raa, Ra, R3, R4, R5, and R6have the same meaning as in any embodiment of Formula (I) described herein. In other words, Formula (I) can be replaced with Formula (II) in any of the above described embodiments, as the skilled person will readily understand. Preferably, the compound of Formula (I) is not this compound: (S)-5-((((5-(2,2'-dimethyl-3'-(3-(((((S)-5-oxopyrrolidin-2-yl)methyl)amino)methyl)- [1,2,4]triazolo[4,3-a]pyridin-6-yl)-[1,1'-biphenyl]-3-yl)-3-methoxypyrazin-2- yl)methyl)amino)methyl)pyrrolidin-2-one Some embodiments of the present invention disclose a compound having Formula I wherein the compound is selected from: 2-(((2',2''-dichloro-3''-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)- [1,1':3',1''-terphenyl]-4-yl)methyl)amino)ethan-1-ol (S)-1-(((6-(2,2'-dichloro-3'-(2-((((S)-2-hydroxypropyl)amino)methyl)-[1,2,4]triazolo[1,5- a]pyridin-7-yl)-[1,1'-biphenyl]-3-yl)-2-methoxypyridin-3-yl)methyl)amino)propan-2-ol; 3-(((6-(2,2'-dichloro-3'-(2-(((3-hydroxypropyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7- yl)-[1,1'-biphenyl]-3-yl)-2-methoxypyridin-3-yl)methyl)amino)propan-1-ol; (R)-1-(((6-(2,2'-dichloro-3'-(2-((((R)-2-hydroxypropyl)amino)methyl)-[1,2,4]triazolo[1,5- a]pyridin-7-yl)-[1,1'-biphenyl]-3-yl)-2-methoxypyridin-3-yl)methyl)amino)propan-2-ol; N-(2-(((7-(3'-(5-(((2-acetamidoethyl)amino)methyl)-6-methoxypyridin-2-yl)-2,2'-dichloro- [1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)ethyl)acetamide; 2-(((6-(2,2'-dichloro-3'-(2-(((1-hydroxy-2-methylpropan-2-yl)amino)methyl)- [1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1'-biphenyl]-3-yl)-2-methoxypyridin-3-yl)methyl)amino)- 2-methylpropan-1-ol; 2-(((6-(2,2'-dichloro-3'-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)- [1,1'-biphenyl]-3-yl)-2-isopropoxypyridin-3-yl)methyl)amino)ethan-1-ol. 2-(((6-(2,2'-dichloro-3'-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)- [1,1'-biphenyl]-3-yl)-2-ethoxypyridin-3-yl)methyl)amino)ethan-1-ol. Certain features of the invention that are described in separate embodiments, can also be provided in combination in a single embodiment. Thus, it is contemplated that features described as embodiments of the compounds of Formula (I) can be combined in any suitable combination. The compounds described and claimed herein can have one or more stereocenters and can be isolated in enantiopure form (optically active) or as stereomeric mixtures, such as racemic forms. Methods on how to obtain enantiopure compounds with enantioselective synthesis and / or from optically inactive starting materials are known in the art. Cis and trans geometric isomers of the compounds of the present invention may be isolated as a mixture of isomers or as separated isomeric forms. In some embodiments, the compounds of the invention have the (R)-configuration. In other embodiments, the compounds have the (S)-configuration. In compounds with more than one chiral center, each of the chiral centers may be independently (R) or (S). The term "compound" as used herein, includes all geometric isomers, and stereoisomers, of the structures depicted. The present invention also includes pharmaceutically acceptable salts of the compounds described herein. The pharmaceutically acceptable salts of the present invention include the generally regarded as safe (GRAS) salts of the parent compound formed, e.g., from GRAS inorganic or organic acids. All compounds, and pharmaceutically acceptable salts thereof, can be found as such or with other substances such as water and solvents. This in turn means that in the solid state, the compounds described herewith, and salts thereof may occur in various forms, e.g., taking the form of solvates, including hydrates. So, unless indicated otherwise, reference in the specification to compounds and salts thereof should be understood as encompassing any solid state form of the compound (e.g., polymorph or solvate). The compounds of the present inventions or salts thereof can be substantially or partially isolated / purified from the environment in which they were formed or detected. This can be done via a purification process, according to methods known in the art. The term substantially purified compound refers to compositions containing at least 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 99% by weight of the compounds of the invention, or salt thereof. Medical uses For brevity, the uses and methods will be described simply referring to “the compound of the invention” or “compounds of the invention”. It is understood that for the medical uses described herewith, any of the compounds disclosed herein, including any of the embodiments thereof, may be used. In particular, the “compound of the invention” or “compounds of the invention” are any compound or compounds according to Formula (I) as disclosed herein. The compounds of the invention are for use as a medicament. The compound of the invention, or a pharmaceutically acceptable salt or a stereoisomer thereof, or a composition of the invention comprising the compound of the invention, or a pharmaceutically acceptable salt or a stereoisomer thereof, can be for use in a method of treating a disease or disorder associated with inhibition of PD-1 / PD-L1 interaction wherein the disease or disorder is cancer or an infection. Compounds of the present invention can inhibit the activity of PD-1 / PD-L1 protein / protein interaction and are therefore useful in treating diseases and disorders associated with activity of PD-1 / PD-L1 interaction. Accordingly, the present invention provides the compound of the invention and a composition comprising the compound of the invention for use in methods of inhibiting PD-1 / PD-L1 interaction, said methods comprising administering to a patient in need thereof a compound of the invention, or a pharmaceutically acceptable salt or a stereoisomer thereof. The compound of the invention, or a pharmaceutically acceptable salt or a stereoisomer thereof, or a composition of the invention comprising the compound of the invention, or a pharmaceutically acceptable salt or a stereoisomer thereof, can further be for use in a method of enhancing, stimulating and / or increasing the immune response in a patient, wherein the patient has cancer or an acute or chronic infection. The compounds of the present invention can be used alone, in combination with other agents or therapies or as an adjuvant for the treatment of diseases or disorders, including cancer or infection diseases.The compound of the invention induces a reversion of T cell exhaustion, that may occur incancer or infections. The experiments described herein demonstrate that the compound of the invention inhibits the PD-1 / PD-L1 interaction in vitro and / or in vivo, in cancerous cells and during infections. The blockade of PD-1 enhances the immune response to cancerous cells and infectious diseases in mammals, humans included. In some embodiments, provided herein, are the compound of the invention and a composition comprising the compound of the invention for use in a method for treating cancer. In one embodiment, the present disclosure provides the compound of the invention and a composition comprising the compound of the invention for use in a method for inhibiting growth of tumor cells. In some embodiments provided herein, is a method for treating cancer, said method including administering the compound of the invention or a composition comprising the compound of the invention to a subject in need thereof. In some embodiments provided herein, is a method for inhibiting growth of tumor cells, said method including administering the compound of the invention or a composition comprising the compound of the invention to a subject in need thereof. The compound of the invention can be for use in the treatment of all types of cancers where there is an over-expression of PD-L1. Non-limiting examples of cancers that are treatable using the compound of the present invention are MSI-H / dMMR colorectal cancer. PM, pleural mesothelioma, TNBC, triple-negative breast cancer, CSCC, cutaneous squamous cell carcinoma, TMB-H, tumor mutation burden high, CRC, colorectal cancer, BCG-BC, Bacillus Calmette-Guérin bladder cancer, EC, endometrial carcinoma, ESCC, esophageal squamous cell carcinoma, SCLC, small cell lung cancer, RCC, renal cell carcinoma, MCC, Merkel cell carcinoma, HCC, hepatocellular carcinoma, PMBCL, primary mediastinal large B cell lymphoma, CC, cervical cancer, GC, gastric cancer, MSI-H, microsatellite instability high, dMMR, mismatch repair-deficient, UC, urothelial carcinoma, cHL, classical Hodgkin’s lymphoma, HNSCC, head and neck squamous cell carcinoma, NSCLC, non-small cell lung cancer. PD-1 pathway blockade with compounds of the present invention can also be useful for treating infections. Accordingly, the compound of the invention can be for use in a method for treating infections. The compound of the invention can be for use in the treatment of all types of infections where there is an over-expression of PD-1 / PD-L1. These can be viral, bacterial, fungal and / or parasite infections. Non-limiting examples of infections that are treatable with the compound of the invention are chronic hepatitis B, chronic hepatitis C, chronic hepatitis D, HIV and SIV, Covid and other infections caused by coronaviruses, as well as infections caused by herpes simplex virus, cytomegalovirus, Kaposi’s sarcoma-associated herpesvirus, varicella zoster virus and other herpesviruses, influenza virus, lymphocytic choriomeningitis virus, Japanese encephalitis virus, Ebola virus, hantavirus, Friend retrovirus, respiratory syncytial virus, rabies virus, as well as tuberculosis, malaria, candida albicans, helicobacter pylori, staphylococcus aureus, pseudomonas aeruginosa, borrelia, burgdorferi, sepsis. In one embodiment the present disclosure provides the compound of the invention and a composition comprising the compound of the invention for use in a method for treating bacterial infections. In one embodiment the present disclosure provides the compound of the invention and a composition comprising the compound of the invention for use in a method for treating virus infections. In one embodiment the present disclosure provides the compound of the invention and a composition comprising the compound of the invention for use in a method for treating chronic infections. In one embodiment the present disclosure provides the compound of the invention and a composition comprising the compound of the invention for use in a method for treating acute infections. In one embodiment the present disclosure provides a method for treating virus infections, said method including administering the compound of the invention or a composition comprising compound of the invention to a subject in need thereof. In one embodiment the present disclosure provides a method for treating bacterial infections, said method including administering the compound of the invention or a composition comprising the compound of the invention to a subject in need thereof. In one embodiment the present disclosure provides a method for treating chronic infections, said method including administering the compound of the invention or a composition comprising the compound of the invention to a subject in need thereof. In one embodiment the present disclosure provides a method for treating acute infections, said method including administering the compound of the invention or a composition comprising the compound of the invention to a subject in need thereof. Formulation, Dosage Forms and Administration This invention also relates to pharmaceutical compositions comprising the compound of the present invention or a pharmaceutically acceptable salt thereof, in combination with one or more pharmaceutically acceptable carriers or excipients. In these compositions, the compound of the invention is used as an active ingredient. Thus, the present disclosure provides a composition comprising a compound of Formula (I) or any of the formulas as described herein, or a pharmaceutically acceptable salt thereof, or any of the embodiments thereof, and at least one pharmaceutically acceptable carrier or excipient. These compositions can be prepared according to methods known in the art and can be administered by any route appropriate to the condition to be treated. For example, suitable routes include topical, transdermal, parenteral, nasal, oral, rectal, and the like. It will be appreciated that the preferred route may vary with, for example, the condition of the recipient. Particularly preferred and advantageous is the oral administration. The compounds according to the invention can be easily and safely administered by oral administration. In making the compositions of the invention, the active ingredient is typically mixed with an excipient, diluted by an excipient or enclosed within such a carrier in the form of, e.g., a tablet, capsule, sachet, paper, or other container (liquid, solid, spray). Tablets, capsules and other formulation suitable for oral administration are particularly preferred. Some examples of suitable excipients include microcrystalline cellulose, polyvinylpyrrolidone, cellulose, lactose, dextrose, sucrose, alginates, gelatin, calcium silicate, water, sorbitol, mannitol, starches, gum acacia, calcium phosphate, syrup and methyl cellulose. The formulations can include emulsifying and suspending agents; preserving agents such as methyl- and propylhydroxy-benzoates; sweetening agents; and flavoring agents. The compositions can also include lubricating agents such as talc, magnesium stearate and mineral oil; wetting agents; The compositions of the invention can be formulated by employing procedures known in the art.General synthesis. In another aspect, the present invention refers to processes for obtainingthe compounds according to the invention. Examples of the general procedures for obtaining the compounds of the invention, and of the synthetic routes for preparing them as well as their intermediate compounds are explained below. EXAMPLES Compounds of the invention can be prepared using known organic synthesis techniques. The skilled person can easily select the suitable solvents, temperatures and starting materials, as well as the suitable synthetic routes. Abbreviations: ACN - Acetonitrile DCM - Dichloromethane EA - Ethyl acetate EtOH - Ethanol Ex - Example FA - Formic acid H - Hour / s HPLC - High performance liquid chromatography KOAc - Potassium acetate LC-MS - Liquid chromatography - Mass spectrometry MeOH - Methanol NMR - Nuclear Magnetic Resonance Pd2(dba)3- Tris(dibenzylideneacetone)dipalladium(0) Pd(PPh3)4- Tetrakis(triphenylphosphine)palladium(0) PdCl2(dppf) -[1,1 '-Bis (diphenylphosphino)ferrocene]dichloropalladium(II) PdCl2(dppf).dcm - [1,1 '-Bis (diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex Prep-HPLC - Preparative high pressure liquid chromatography RT - Room temperature Sat. - Saturated SFC - Supercritical fluid chromatography SM - Starting material TEA - Triethylamine TFA - Trifluoroacetic acid THF - Tetrahydrofuran General considerations and Analytical Methods: The compounds used in the reaction processes, if not mentioned otherwise, were commercially available. All compounds were characterized by NMR, HPLC and LC-MS (ESI+APCI). NMR data were obtained on Varian 400 MHz spectrometer, all chemical shifts were reported in parts per million (ppm) and were measured relative to TMS. LCMS (ESI+APCI) measurements were performed on Shimadzu LCMS 2020 with N- Series mass spectrometer. The yields of the compounds provided refer to isolated compounds. All compounds were purified or enantiomers separation by using one of the below mentioned methods. Reverse phase HPLC Purification methods: 1. The crude compound was subjected purification by reverse phase HPLC, Inertsil ODS3V column (250 x 20) mm, 5.0 µm; mobile phase (A: B), A = 0.1% FA in H2O, B = ACN 100%. 2. The crude compound was subjected purification by reverse phase HPLC, Inertsil ODScolumn (250 x 20) mm, 5.0 µm; mobile phase (A: B), A = 0.1% FA in H2O, B = ACN:MeOH (1:1) 100%. 3. The crude compound was subjected purification by reverse phase HPLC, X-Bridge C18column (250 x 19) mm, 5.0 µm; mobile phase (A: B), A = 0.1% FA in H2O, B = ACN 100%. 4. The crude compound was subjected purification by reverse phase HPLC, X-Bridge C18column (250 x 20) mm, 5.0 µm; mobile phase (A: B), A = 0.1% FA in H2O, B = ACN:MeOH (1:1) 100%. 5. The crude compound was subjected purification by reverse phase HPLC, Triart C18column (250 x 21) mm, 5.0 µm; mobile phase (A: B), A = 10 mmol ABC in H2O, B = ACN:MeOH (1:1) 100%. 6. The crude compound was subjected purification by reverse phase HPLC, X-Bridge C18column (250 x 20) mm, 5.0 µm; mobile phase (A: B), A = 10 mmol ABC in H2O, B = ACN:MeOH (1:1) 100%. 7. The crude compound was subjected purification by reverse phase HPLC, X-Bridge C18column (250 x 20) mm, 5.0 µm; mobile phase (A:B), A = 10 mmol ABC in H2O, B = ACN 100%. SFC Purification methods: 1. The racemic compound was subjected to chiral separation by SFC, dissolved intetrahydrofuran: methanol (1:1)}, column chiral Pak IG (250 x 21) mm, 5.0 µm; mobile phase 55:45 (A:B).A = Liquid CO2, B = Acetonitrile: Methanol (MeOH) (1:1), flow rate: 45 mL / min; Wavelength 233 nm. 2. The racemic compound was subjected to chiral separation by SFC, in tetrahydrofuran(THF): methanol (MeOH) (1:1)}, column chiral Pak IC (250 x 21) mm, 5.0 µm; mobile phase 60:40(A:B). A = Liquid CO2, B = 0.2% triethyl amine in methanol (MeOH), flow rate: 40 mL / min; Wavelength 254 nm Chiral HPLC Purification methods: 1. The racemic compound was subjected to chiral separation by normal phase HPLC,column chiral Pak IG (250 * 21) mm, 5.0 µm; mobile phase 60:40 (A: B). A=0.1%TFA in n-Hexane, B= EtOH(1:1). Example 1: 2-(((2',2''-dichloro-3''-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5- a]pyridin-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)ethan-1-ol The compound of Example 1 was synthesized via the route shown in the scheme below. Step-1: 2-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinaldehyde A mixture of 6-chloro-2-methoxynicotinaldehyde (5.0 g, 29 mmol), bis(pinacolato)diborane (8.8 g, 34 mmol) in 1,4-dioxane (100 mL) was added KOAc (8.5 g, 87 mmol). The resulting solution was degassed with N2 for 20 minutes and added Pd(dppf)Cl2.DCM (2.3 g, 2.9 mmol) to the reaction mixture and heated the reaction at 95 °C for 2 h. Reaction mixture was allowed to cool to room temperature, diluted with EA, filtered through celite bed, and washed with EA (3 x 100 mL). The combined organic layer was dried over sodium sulphate, filtered, and evaporated to obtain the title compound (7.0 g) as a black liquid. LC-MS calculated for C13H18BNO4(M+H)+: m / z = 263.13; found: 264.151H NMR (500 MHz, CDCl3): δ: 10.395 (s, 1H), 8.054 (d, J = 7 Hz, 1H), 7.540 (d, J = 7.5 Hz, 1H),4.153 (s, 3H), 1.386 (s, 12H). Step-2: 6-(3-bromo-2-chlorophenyl)-2-methoxynicotinaldehyde A mixture of 2-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinaldehyde (5.0g, 18 mmol), 1,3-dibromo-2-chlorobenzene 3 (7.5 g, 28 mmol), in 1,4-dioxane (60 mL) wasadded potassium carbonate (7.4 g, 54 mmol) in water (15 mL), degassed with N2for 20 minutes. Pd(dppf)Cl2(2.40 g, 3.3 mmol) was added and heated the reaction at 95 °C for 3 h. The reaction mixture was allowed to cool to room temperature and diluted with EA (200 mL) and water (300 mL). The organic layer was separated, aqueous layer was extracted with EA (3 x 150 mL). The combined organic layer was dried over sodium sulphate, filtered, and evaporated. Crude material was purified by Biotage flash column chromatography using (0- 20%) EA in hexane to obtain the title compound (2 g, 33%) as a white solid. LC-MS calculated for C13H9BrClNO2(M+2) +: m / z = 326.5; found: 328.01H NMR (500 MHz, CDCl3): δ: 10.419 (s, 1H), 8.19 (d, J = 6 Hz, 1H), 7.73 (d, J = 1.1 Hz, 1H),7.52 (d, J = 1.2 Hz, 1H), 7.31 (d, J = 7.5 Hz, 1H), 7.24 (t, J = 9.0 Hz, 1H), 4.10 (s, 3H). Step-3: 6-(2-chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2- methoxynicotinaldehydeTo a mixture of 6-(3-bromo-2-chlorophenyl)-2-methoxynicotinaldehyde (1.8 g, 5.5 mmol),bis(pinacolato)diborane (2.1 g, 8.2 mmol), in 1,4-dioxane (30 mL) KOAc (1.6 g, 16 mmol) was added, and the mixture was degassed with N2 for 20 minutes. Pd(dppf)Cl2. DCM (0.4 g, 0.5 mmol) was added, heated the reaction heated at 95°C for 3 h. The resulting reaction mixture was cooled to room temperature, diluted with EA, filtered through celite bed, and washed with EA (3 x 100 mL). The combined organic layer was dried over sodium sulphate, filtered, and evaporated and the crude product was purified by Biotage flash column chromatography using (0-10%) EA in hexanes to obtain the title compound (1.5 g, 75 %) as a yellow liquid. LC-MS calculated for C19H21BClNO4 (M+H) +: m / z = 373.3; found: 374.1. 1H NMR (500 MHz, CDCl3): δ: 10.4 (s, 1H), 8.16 (d, J = 4.4 Hz, 1H), 7.72 (dd, J1 = 2.0, J2 = 7.0 Hz, 1H), 7.62 (dd, J1 = 2.0, J2 = 7.0 Hz, 1H), 7.37-7.32 (m, 2H), 4.09 (s, 3H), 1.39 (s, 12H). Step-4: 6-(3'-bromo-2,2'-dichloro-[1,1'-biphenyl]-3-yl)-2-methoxynicotinaldehyde To a mixture of 6-(2-chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2- methoxynicotin aldehyde (2.5 g, 6.7 mmol), 1,3-dibromo-2-chlorobenzene (3.0 g, 12 mmol), in 1,4-dioxane (30 mL) potassium carbonate (2.8 g, 2.0 mmol) and water (5 mL) were added, and the mixture was degassed with N2 for 20 minutes. Pd(dppf)Cl2 (0.48 g, 0.67 mmol) was added then heated the reaction at 95 °C for 2 h. The reaction mixture was cooled to room temperature and diluted with EA, filtered through celite bed and washed with EA (3 x 100 mL). The combined organic layer was dried over sodium sulphate, filtered, and evaporated. The crude material was purified by combi flash column chromatography using (0-10%) EA in hexanes to obtain the title compound (1.1 g, 38 %) as a brown solid. LC-MS calculated for C19H12BrCl2NO2(M+H) +: m / z = 437.11; found: 437.9.1H NMR (500 MHz, CDCl3): δ: 10.35 (s, 1H), 8.127 (d, J = 6.4 Hz, 1H), 7.64-7.60 (m, 2H), 7.40-733 (m, 2H), 7.26-7.13 (m, 3H), 4.03 (s, 3H). Step-5: 6-(2,2'-dichloro-3'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1'-biphenyl]-3- yl)-2-methoxynicotinaldehydeTo a mixture of 6-(3'-bromo-2,2'-dichloro-[1,1'-biphenyl]-3-yl)-2-methoxynicotinaldehyde (1.1g, 2.5 mmol), bis(pinacolato)diborane (0.83 g, 3.2 mmol), in 1,4-dioxane (22 mL) KOAc (0.73 g, 7.5 mmol) was added, and the mixture was degassed with N2for 20 minutes. Pd(dppf)Cl2.DCM (0.205 g, 0.25 mmol) was added and the reaction was heated at 90 °C for 3 h. The mixture was allowed to cool to room temperature and diluted with EA (500 mL) and filtered through celite bed, organic were evaporated. The crude material was purified by combi flash column chromatography using (0-10%) EA in hexanes to obtain the title compound (0.72 g, 60 %) as a white sticky mass. LC-MS calculated for C25H24BCl2NO4 (M+H) +: m / z = 483.12; found: 484.11H NMR (500 MHz, CDCl3): δ: 10.41 (s, 1H), 8.18 (d, J =6.4 Hz, 1H), 7.72-7.09 (m, 1H), 7.64 (d,1H), 7.44-7.42 (m, 2H), 7.35-7.30 (m, 3H), 4.13 (s, 2H), 1.39 (s, 12H). Step-6: 7-(2,2'-dichloro-3'-(5-formyl-6-methoxypyridin-2-yl)-[1,1'-biphenyl]-3-yl)- [1,2,4]triazolo[1,5-a]pyridine-2-carbaldehyde To a mixture of 6-(2,2'-dichloro-3'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1'- biphenyl]-3-yl)-2-methoxynicotinaldehyde (0.722 g, 1.5 mmol), 7-chloro-[1,2,4]triazolo[1,5- a]pyridine-2-carbaldehyde (0.32 g, 1.9 mmol), in 1,4-dioxane (55 mL) potassium carbonate (0.703 g, 5.1 mmol) and water (9 mL) were added, and the mixture was degassed with N2 for 10 minutes. Pd(dppf)cl2 (0.730 gm, 0.102 mmol) was added and the reaction was heated at 95 °C for 2h in a sealed tube. The mixture was allowed to cool to room temperature and diluted with EA (50 mL) and filtered through celite bed. The combined organic layers were evaporated and the resulting crude material was purified by combi flash column chromatography using (0-10%) EA in hexane to obtain the title compound (0.40 g, 44 %) as a light brown solid. LC-MS calculated for C26H16Cl2N4O3(M+1)+ m / z = 502.0; found: 503.1. 1H NMR (500 MHz, DMSO-d6): δ: 10.30 (s, 1H), 10.17 (s, 1H), 9.20 (m, 1H), 8.14 (m, 1H), 7.69(s, 1H), 7.65 (m, 1H), 7.63-7.60 (m, 7H), 4.06 (s, 3H). Step-7: 2-(((6-(2,2'-dichloro-3'-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5- a]pyridin-7-yl)-[1,1'-biphenyl]-3-yl)-2-methoxypyridin-3-yl)methyl)amino)ethan-1-ol To a stirred solution of 7-(2,2'-dichloro-3'-(5-formyl-6-methoxypyridin-2-yl)-[1,1'-biphenyl]-3- yl)-[1,2,4]triazolo[1,5-a]pyridine-2-carbaldehyde (2 g, 4.42 mmol) and ethanol amine (2 g, 33mmol) in methanol (10 mL), ZnCl2(1.75 g, 1.26 mmol) and NaBH3CN (0.79 g, 1.26 mmol) were added. The resulting reaction was heated at 60 oC for 3 h. Organic volatiles were removedunder reduce pressure and the crude material was purified by prep-HPLC (INT ODS 3V-C18 (4.6*250) mm,5μ; mobile phase (A: B), A = 0.1% Formic acid in water, B = Acetonitrile). The pure fractions were collected and lyophilised to obtain the title compound as a formate salt, which was neutralised with aqueous NaHCO3(30 mL) and extracted with 5% methanol in dichloromethane (3 x 100 mL). The organic phase was dried over anhydrous sodium sulphate and concentrated over reduced pressure to get the title compound (30 mg, 32 %). LC-MS calculated for C30H30Cl2N6O3 (M+1)+: m / z = 593.51; found: 594.85. 1H NMR (500 MHz, DMSO-d6): δ: 8.97 (d, J = 5.6 Hz, 1H), 7.86 (s, 1H), 7.80 (d, J = 7.0 Hz, 1H),7.68 (dd, J1 = 2.0 , J2=8.0 Hz, 1H), 7.59-7.51 (m, 4H), 7.53 (dd, J1 = 2.07.3 Hz, 1H), 7.27 (m, 2H), 4.53 (s, 2H), 3.94 (s, 2H), 3.91 (s, 3H), 3.71 (s, 2H), 3.48 (s, 4H), 2.68-2.60 (m, 4H). The following examples shown in Table 1 were prepared according to similar procedures described for Example 1 by reaction with appropriate amines:Ex.No Structure andLC-MS(ESI) m / z: IUPAC Name LC-MS calculated for C32H34Cl2N6O3 (M+H)+: m / z = 621.56; found: 622.55 1H NMR (500 MHz, DMSO-d6): 8.97 (d, J = 5.6 Hz, 1H,), 7.86 (s, (S)-1-(((6-(2,2'-dichloro-3'-(2-((((S)-2- 1H), 7.81 (d, J = 6 Hz, 1H), 7.62 hydroxypropyl)amino)methyl)- (d, J = 4.8 Hz, 1H), 7.63-7.55 (m, [1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1'- 4H), 7.46 (t, J = 5.5 Hz, 1H),7.27- biphenyl]-3-yl)-2-methoxypyridin-3- 7.24 (m, 2H), 4.51 (d, J = 3.6 Hz, yl)methyl)amino)propan-2-ol 2H), 3.97 (m, 5H), 3.73 (m, 4H), 2.46 (m, 4H), 2.22 (bs, 2H) 1.06- 1.03 (m, 6H). LC-MS calculated for C32H34Cl2N6O3 (M / 2+1)+: m / z = 621.56; found: 311.2 (observed monomer mass). 1H NMR (500 MHz, DMSO-d6): 8.97 (d, J = 5.2 Hz, 1H,), 7.85 (s, 3-(((6-(2,2'-dichloro-3'-(2-(((3- 1H), 7.80 (d, J = 8 Hz, 1H), 7.68- hydroxypropyl)amino)methyl)- 7.56 (m, 5H), 7.47 (t, J = 6 Hz, [1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1'- 1H), 7.25 (q, J = 8 Hz, 2H), 4.4 biphenyl]-3-yl)-2-methoxypyridin-3- (bs, 2H), 3.91 (d, J = 3.0 Hz, 5H), yl)methyl)amino)propan-1-ol 3.67 (s, 2H), 3.49-3.45 (m, 4H), 2.65 (s, 2H), 2.62-2.59 (m, 2H), 1.60-1.56 (m, 4H). LC-MS calculated for C32H34Cl2N6O3: m / z = 621.56; found: 621.21 (M)+1H NMR (500 MHz, DMSO-d6): 8.97 (d, J=5.6 Hz, 1H,), 7.86 (s, (R)-1-(((6-(2,2'-dichloro-3'-(2-((((R)-2- 1H), 7.81 (d, J = 6 Hz, 1H), 7.69 hydroxypropyl)amino)methyl)- (d, J = 4.8 Hz, 1H), 7.63-7.55 (m, [1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1'- 4H), 7.51 (d, J = 2.8 Hz, 1H), 7.27- biphenyl]-3-yl)-2-methoxypyridin-3- 7.25 (m, 2H), 4.51 (t, J = 9 Hz, yl)methyl)amino)propan-2-ol 2H), 3.94-3.89 (m, 5H), 3.70 (t, J = 2.5 Hz, 4H), 2.47 (t, J = 2.5 Hz, 4H), 1.06-1.03 (m, 6H). LC-MS calculated for C34H36Cl2N8O3 (M / 2+1)+: m / z = 675.62; found: 338.2 (observed monomer mass). 1H NMR (500 MHz, DMSO-d6): 8.97 (d, J = 5.6 Hz, 1H,), 7.86- N-(2-(((7-(3'-(5-(((2- 7.81 (m, 4H), 7.68 (d, J = 6.4 Hz, acetamidoethyl)amino)methyl)-6- 1H), 7.66-7.54 (m, 4H), 7.53 (d, J methoxypyridin-2-yl)-2,2'-dichloro-[1,1'- = 9.6 Hz, 1H), 7.27 (m, 2H), 3.92 biphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin- (d, J = 3.6 Hz, 6H), 3.69 (s, 2H), 2-yl)methyl)amino)ethyl)acetamide 3.17-3.12 (m, 4H), 2.63 (t, J=6.5 Hz, 2H), 2.58 (t, J = 6.5 Hz, 2H), 1.79 (d, J= 6.0 Hz, 6H). LC-MS calculated for C34H38Cl2N6O3 (M+H)+: m / z = 649.62; found: 651.15. 1H NMR (500 MHz, DMSO-d6): 8.96 (d, J = 5.6 Hz, 1H,), 7.87 (d, J = 6.8 Hz, 2H), 7.67 (d, J = 6 Hz, 2-(((6-(2,2'-dichloro-3'-(2-(((1-hydroxy-2- 1H), 7.62-7.54 (m, 4H), 7.45 (d, J methylpropan-2-yl)amino)methyl)- = 6 Hz, 1H), 7.26 (d, J = 6 Hz, 2H), [1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1'- 4.69 (s, 1H), 4.56 (t, J = 5.5 Hz, biphenyl]-3-yl)-2-methoxypyridin-3- 1H), 3.91 (d, J = 10.5 Hz, 5H), yl)methyl)amino)-2-methylpropan-1-ol 3.64 (s, 2H), 3.24 (d, J = 4.0 Hz, 4H), 2.01 (s, 1H), 1.90 (s, 1H), 1.02 (s, 12H). Example 7: 2-(((6-(2,2'-dichloro-3'-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5- a]pyridin-7-yl)-[1,1'-biphenyl]-3-yl)-2-isopropoxypyridin-3-yl)methyl)amino)ethan-1-ol The compound of Example 7 was synthesized via the route shown in the scheme below. Step-1: 6-chloro-2-isopropoxynicotinic acidNaH (3.1 g, 130 mmol) was added portion wise at 0 oC to a stirred solution of tert-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylate (3.0 g, 12.9 mmol) in IPA (10 mL, 130 mmol) and THF(100 mL). The reaction mixture was stirred at 0 oC for 30 minutes and 2,6-dichloronicotinicacid (5 g, 26 mmol) was added. The resulting reaction was heated at 60°C for 16 h and then cooled to room temperature. The mixture was evaporated to a half and then diluted with 0.1N NaOH solution (200 mL) and washed with diethyl ether (200 mL). The aqueous layer was acidified with 0.5N HCl solution to pH 2 and extracted with DCM (3 x 200 mL). The combined organic layers were dried over sodium sulphate, filtered, and evaporated to obtain the title compound (5.0 g, crude) as a yellow solid. LC-MS calculated for C9H10ClNO3(M+H) +: m / z = 215.0; found:215.9.1H NMR (500 MHz, DMSO-d6): δ: 13.01 (s, 1H), 8.11 (d, J = 7.5 Hz, 1H), 7.13 (d, J = 8.0 Hz, 1H),5.26 (m, 1H), 1.31 (d, J = 6 Hz, 6H). Step-2: Methyl 6-chloro-2-isopropoxynicotinate To a mixture of 6-chloro-2-isopropoxynicotinic acid (5 g, 23 mmol) in MeOH (100 mL) was added thionyl chloride (5.0 mL, 66 mmol) under N2and the reaction mixture heated at 80 °C for 3 h. The mixture was cooled to room temperature and organic volatiles were evaporated. The resulting crude material was purified by Biotage flash column chromatography using (0- 10%) EA in hexanes to obtain the title compound (2.2 g, 40%) as a colourless liquid. LC-MS calculated for C10H12ClNO3 (M+H) +: m / z = 229.0; found:229.6.1H NMR (500 MHz, CDCl3): δ: 8.09 (d, J = 7.5 Hz, 1H), 6.91 (d, J = 8.0 Hz, 1H), 5.41 (m, 1H),3.87 (s, 3H), 1.40 (d, J = 6 Hz, 6H). Step-3: (6-chloro-2-isopropoxypyridin-3-yl)methanol DIBAL-H (1M, 48 mL, 48 mmol) was added at -20°C to a stirred solution of methyl 6-chloro-2- isopropoxynicotinate (4.4 g, 19 mmol) in DCM (100 mL). After being stirred at room temperature for 2 h, the reaction mixture was quenched with NH4Cl solution (100 mL) and EA (200 mL) was added. The mixture was filtered through celite bed and washed with EA (2 x 100 mL). The combined organic layers were dried over Na2SO4, filtered, and evaporated to obtain the title compound (3.5 g, crude) as a colourless liquid. LC-MS calculated for C9H12ClNO2 (M+H) +: m / z = 201.6; found:202.1.1H NMR (500 MHz, CDCl3): δ: 7.51 (d, J = 7.5 Hz, 1H), 6.86 (d, J = 7.5 Hz, 1H), 5.38 (t, J = 6 Hz,1H), 4.60 (d, J = 6 Hz, 2H), 2.24(t, J = 6.5 Hz, 1H), 1.36 (d, J = 6.5 Hz, 6H). Step-4- 6-chloro-2-isopropoxynicotinaldehyde To a stirred solution of (6-chloro-2-isopropoxypyridin-3-yl)methanol (3.5 g, 17 mmol), in DCM (70 mL) DMP (9.5 g, 22 mmol) was added portion wise at 0°C under N2. The reaction was stirred at room temperature for 2 h. After completion, the reaction mixture was diluted with NaHCO3solution (100 mL) and extracted with DCM (3 x 100 mL). The combined organic layers were dried over sodium sulphate, filtered, and evaporated. The crude material was purified by combi flash column chromatography using (0-5%) EA in hexane to obtain the titlecompound (2.7 g, 79 %) as a white solid.LC-MS calculated for C9H10ClNO2 (M+H) +: m / z = 199.6; found: 200.1.1H NMR (500 MHz, CDCl3): δ: 10.3 (s, 1H), 8.04 (d, J = 8 Hz, 1H), 6.97 (d, J = 7.5 Hz, 1H), 5.48(m, 1H), 1.42 (d, J = 6.5 Hz, 6H). Step-5: 6-(3-bromo-2-chlorophenyl)-2-isopropoxynicotinaldehyde A mixture of 6-chloro-2-isopropoxynicotinaldehyde (1.0 g, 5 mmol), 2-(3-bromo-2- chlorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.7 g, 5.5 mmol), K2CO3 (1.7 g, 12.5 mmol) and water (4 mL), in 1,4-dioxane (16 mL) was degassed with N2 for 10 minutes. Pd(dppf)cl2 (0.40 gm, 0.35 mmol) was added, and the reaction was heated at 60 °C for 3 h in a sealed tube. The reaction mixture was cooled to room temperature, diluted with water (100 mL) and extracted with EA (3 x 100 mL). The combined organic layers were dried over Na2SO4, filtered, and evaporated. The crude material was purified by combi flash column chromatography using (2-5%) EA in hexane to obtain the title compound (0.80 g, 47 %) as a colourless liquid. LC-MS calculated for C15H13BrClNO2 (M+H) +: m / z = 354.6; found:355.65.1H NMR (500 MHz, CDCl3): δ: 10.4 (s, 1H), 8.19-8.15 (m, 1H), 7.72 (dd, J1 =1.5, J2= 8.0 Hz, 1H),7.48 (t, J=,1.5 Hz, 1H), 7.24 (q, J=7.0 Hz, 2H), 5.54 (m, 1H), 1.428 (s, 6H). Step-6: 6-(2,2'-dichloro-3'-hydroxy-[1,1'-biphenyl]-3-yl)-2-isopropoxynicotinaldehydeTo a mixture of 6-(3-bromo-2-chlorophenyl)-2-isopropoxynicotinaldehyde (0.8 g, 2.2 mmol)and 2-(3-bromo-2-chlorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.74 g, 2.9 mmol), in 1,4-dioxane (16 mL) K2CO3(0.77 g, 5.6 mmol) and water (6 mL) were added. The mixture was degassed with N2for 10 minutes and Pd(dppf)cl2(0.115 gm, 0.15 mmol) was added. The reaction was heated at 90 °C for 3h in a sealed tube. The reaction mixture was cooled to room temperature, diluted with water (100 mL) and extracted by EA (3 x 100 mL). The combined organic layers were dried over sodium sulphate, filtered, and evaporated. The crude material was purified by combi flash column chromatography using (2-5%) EA in hexanes to obtain the title compound (0.80 g, 88 %) as a white solid. LC-MS calculated for C21H17Cl2NO3 (M+1)+: m / z = 401.06; found: 402.10.1H NMR (500 MHz, CDCl3): δ: 10.4 (s, 1H), 8.18 (d, J = 8 Hz, 1H), 7.62 (dd, J1= 1.5, J2= 7.5 Hz,1H), 7.44 (t, J = 8.0 Hz, 1H), 7.35-7.25 (m, 3H), 7.10 (dd, J1 = 1.5, J2= 8.0 Hz, 1H), 6.901 (dd, J1 = 1.5, J2= 7.5 Hz, 1H), 5.76 (s, 1H), 5.563 (m, 1H), 1.440 (m, 6H).Step-7: 2,2'-dichloro-3'-(5-formyl-6-isopropoxypyridin-2-yl)-[1,1'-biphenyl]-3-yltrifluoromethanesulfonate A mixture of 6-(2,2'-dichloro-3'-hydroxy-[1,1'-biphenyl]-3-yl)-2-isopropoxynicotinaldehyde (0.8 g, 1.9 mmol), and DIPEA (069 mL, 3.9 mmol) in DCM (16 mL) Tf2O (0.38 mL, 2.3 mmol) was added dropwise at 0° C. After being stirred at 0°C for 2h the reaction mixture was diluted with water (100 mL) and extracted by DCM (50 mL x3). The combined organic layers were dried over sodium sulphate, filtered, and evaporated. The crude material was purified by combi flash column chromatography using (2-10%) EA in hexane to obtain the title compound (0.55 g, 52 %) as colourless liquid. LC-MS calculated for C22H16Cl2F3NO5S (M+1)+: m / z = 533.0; found: 534.10.1H NMR (500 MHz, CDCl3): δ: 10.4 (s, 1H), 8.18 (d, J = 7.5 Hz, 1H), 7.66 (dd, J1 =2.0, J2= 8.0Hz, 1H), 7.49-7.44 (m, 3H), 7.38-733 (m, 3H), 5.58 (t, J = 6.0 Hz, 1H), 1. (m, J = 6.0 Hz, 6H). Step-8: 6-(2,2'-dichloro-3'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1'-biphenyl]-3- yl)-2-isopropoxynicotinaldehyde To a mixture of 2,2'-dichloro-3'-(5-formyl-6-isopropoxypyridin-2-yl)-[1,1'-biphenyl]-3-yl trifluoromethanesulfonate (0.55 g, 1.0 mmol), bis(pinacolato)diborane (0.33 g, 1.3 mmol), in 1,4-dioxane (12 mL) KOAc (0.29 g, 3.0 mmol) was added and the mixture was degassed with N2 for 10 minutes. Pd(dppf)cl2 (0.15 gm, 0.7 mmol) was added then the reaction heated at 100°C for 16 h under N2. The reaction mixture was cooled to room temperature and diluted with EA (100 mL), filtered through celite bed and washed with EA (100 mL). The combined organic layers were dried over sodium sulphate, filtered, and evaporated. The crude material was purified by combi flash column chromatography using (10-15%) EA in hexane to obtain the title compound (0.45 g, 86 %) as a yellow solid. LC-MS calculated for C27H28BCl2NO4 (M+2)+: m / z = 512.34; found: 514.1H NMR (500 MHz, CDCl3): δ: 10.4 (s, 1H), 8.16 (d, J = 8 Hz, 1H), 7.72 (dd, J1 =2.5, J2= 6.5 Hz,1H), 7.60 (dd, J1 =2.0, J2 = 8.0 Hz, 1H), 7.41 (t, 8.0 Hz, 1H), 7.35-7.26 (m, 4H), 5.59 (m, 1H), 1.43 (s, 6 H), 1.39 (s, 12H). Step-9: 7-(2,2'-dichloro-3'-(5-formyl-6-isopropoxypyridin-2-yl)-[1,1'-biphenyl]-3-yl)- [1,2,4]triazolo[1,5-a]pyridine-2-carbaldehyde The title compound was prepared in a similar way as Example 1 (step 6) and obtained (200 mg, 45 %) as a pale-yellow solid. LC-MS calculated for C28H20Cl2N4O3(M+H2O)+: m / z =530.0; found:549.1.1H NMR (500 MHz, DMSO-d6): δ: 10.30 (s, 1H), 10.17 (s, 1H), 9.19 (d, J= 7.0 Hz, 1H), 8.16 (q,J= 8.0 Hz, 2H), 7.90-7.51 (m, 7H), 7.42 (d, J= 7.5 Hz, 1H), 5.49-5.44 (m, 1H), 140-1.38 (m, 6H). Step-10: 2-(((6-(2,2'-dichloro-3'-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5- a]pyridin-7-yl)-[1,1'-biphenyl]-3-yl)-2-isopropoxypyridin-3-yl)methyl)amino)ethan-1-ol The title compound was prepared in a similar way as Example 1 (step 7) and obtained (40 mg, 17 %) as white solid. LC-MS calculated for (M+H)+: m / z =620.2; found:621.2.1H. NMR (500 MHz, DMSO-d6): 8.96 (d, J = 7.0 Hz, 1H ), 7.85 (s, 1H), 7.77 (d, J =7.5 Hz, 1H), 7.64- 7.51 ( m, 5H), 7.43 (t, J = 6.0Hz, 1H), 7.26-7.19 (m, 2H), 5.31(m, 1H), 4.49 (q, J = 8 Hz, 2H), 3.94 (s, 1H), 3.68 (s, 2H), 3.491 (m, 4H), 2.68-2.59 (m, 4H), 2.40 (bs, 2H), 1.32-131 (m, 6H). The following example shown in Table 2 was prepared according to a similar procedure described for Example 7. MS: calculated for C31H32Cl2N6O3 607.54; HRMS found 607.2002 1H NMR (500 MHz, DMSO-d6): 8.97 (d, J = 5.6 Hz, 1H), 7.85 (s, 2-(((6-(2,2'-dichloro-3'-(2-(((2- 1H), 7.90 (d, J = 6Hz, 1H), 7.45- hydroxyethyl)amino)methyl)- 7.66 (m, 6H), 7.24 (m, 2H), 4.52 [1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1'- (bs, 2H), 4.38 (q, J = 6.5 Hz, 2H), biphenyl]-3-yl)-2-ethoxypyridin-3- 3.94 (s, 2H), 3.70 (s, 2H), 3.49 ( yl)methyl)amino)ethan-1-ol s, 4H), 2.68-2.60 (m, 4H), 1.33 (t, J = 7.0 Hz, 3H). PD1 / PD-L1 HTRF assay The CisBio HTRF assay kit, purchased from CisBio only, was employed to determine the IC50values of compounds. The PD1 / PD-L1 HTRF assay measures the interactions between the two proteins, PD1 and PD-L1. The interaction is detected by using anti-Tag1 labeled with Europium (HTRF donor) which binds to PD-L1 and anti-Tag2 labeled with XL665 (HTRF acceptor) which binds to PD1. When the two antibodies are in proximity, the excitation of the donor fluorophore results in FRET emission from the acceptor fluorophore. The presence of inhibitors for such an interaction result in reduction of HTRF signal. The assay was conducted in 96-well white assay plates. All the reagents, including Tag1-PD- L1, Tag2-PD1, Anti-Tag1-PD-L1, Anti-Tag2-PD1 were thawed and diluted with PPI Europium Detection buffer to achieve the desired concentration as per the manufacturer’s protocol. A 1000 µM stock solution of test inhibitors was prepared in DMSO. The stock solution was diluted in DMSO to prepare 8 concentrations (1000-0.001 µM). These stock solutions were further diluted in PPI Europium detection buffer to prepare 8 working stock solutions (100- 0.0001 µM). To the 96-well plate, 2 µL of the test inhibitor working stock solutions were added followed by 4 µL of Tag1-PDL1 (5 nM) and 4 µL of Tag2-PD1 (50 nM). The plate was incubated at room temperature for 15 min. Subsequently, 10 µL of pre-mixed Anti-Tag1-PD-L1 and Anti- Tag2-PD1 solution was added. The plate was sealed and incubated at room temperature for 1 h. The HTRF signal was read on Perkin Elmer Envision plate reader using excitation wavelength of 320 nm, emission wavelengths of 620 nm and 665 nm. Results were obtained by calculating the ratio of signal from acceptor at 665 nm to that of signal from donor at 620 nm multiplied by 104. The IC50values were determined by the Hill equation using GraphPad Prism software. Compounds according to the invention as exemplified in the Examples, showed IC50values in the following ranges: +: IC50≤10 nM; ++: 10 nM < IC50≤100 nM; +++: 100 nM < IC50<1000 nM Data obtained for the Example compounds using the PD-1 / PD-L1 homogenous time-resolved fluorescence (HTRF) binding assay described in Examples 1 to 4 is provided in Table 3. Table 3. PD-1 / PD-L1 homogenous time-resolved fluorescence (HTRF) binding assay results for compounds of the invention. Table 3Example HTRF (IC50) Example HTRF (IC50)Example 1 + Example 5 +Example 2 + Example 6 +Example 3 + Example 7 +Example 4 + Example 8 +

Claims

CLAIMS1. A compound of Formula (I) or a pharmaceutically acceptable salt or a stereoisomer thereofFormula I wherein: X1-X4 are each independently C or N, with the proviso that at least three of X1-X4 are N; Y1-Y3 are each independently C or N; with the proviso that at least one of them is N; p is 1-3; q is 1-3; R3 and R5 are each independently methyl, Cl, or CN; R4is H, C1-6alkyl, halogen, or CN; R6is H, C1-6alkyl, halogen, or CN; R7 is C1-4 alkoxy; Raa is H or C1-6 alkyl, or Raa and Ra are linked together to form a 4-10 membered heterocycloalkyl optionally substituted with 1, or 2 independently selected Rdsubstituents; Ra is selected from C1-6 alkyl, C1-6 alkoxy, and C3-10 cycloalkyl, or Raa and Ra are linked together to form a 4-10 membered heterocycloalkyl optionally substituted with 1, or 2 independently selected Rd substituents; and wherein the C1-6 alkyl, C1-6 alkoxy, and C3-10 cycloalkyl of Ra are each independently substituted with 1, or 2 independently selected Rd substituents;Rccis H or C1-6alkyl, or Rccand Rcare linked together to form a 4-10 membered heterocycloalkyl optionally substituted with 1, or 2 independently selected Rdsubstituents; Rc is selected from C1-6 alkyl, C1-6 alkoxy, and C3-10 cycloalkyl, or Rcc and Rc are linked together to form a 4-10 membered heterocycloalkyl optionally substituted with 1, or 2 independently selected Rd substituents; and wherein the C1-6 alkyl, C1-6 alkoxy, and C3-10 cycloalkyl of Rc are each independently substituted with 1, or 2 independently selected Rd substituents; each Rdis independently selected from C1-6alkyl, C1-6alkoxy, C6-10aryl, C3-10cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C3-C6 cyclic amide, CN, NH2, C(O)ORe, NHRe, NReRe, NReC(O)Re, NReC(O)ORe, ORe, (=O), S(O)2Re and S(O)2NReRe, and wherein the C1- 6 alkyl, C1-6 alkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, and C3-C6 cyclic amide of Rd are each optionally substituted with 1, 2, or 3 independently selected Rfsubstituents; each Re is independently selected from H, OH, COOH, C(O)Rf, C1-6 alkyl, and 5-14 membered heteroaryl, wherein the C1-6 alkyl, and 5-14 membered heteroaryl of Re are each optionally substituted with 1, 2 or 3 independently selected Rf substituents; each Rfis independently selected from H, C1-4alkyl, halogen, CN, COOH, OH, and (=O).

2. A compound according to claim 1, or a pharmaceutically acceptable salt or a stereoisomerthereof, wherein the heteroaryl groupselected from the group consistingof:p is 1, and Raa and Ra are as defined in claim 1.

3. A compound of any one of claims 1 or 2, wherein R3 and R5 are Cl; R4, and R6 are H, p is 1,and q is 1.

4. A compound of any one of claims 1-3, or a pharmaceutically acceptable salt or astereoisomer thereof, wherein R7 is methoxy (MeO), ethoxy (OEt) or isopropoxy (PriO).

5. A compound of any one of claims 1-4, wherein Y2 and Y3 are each C and Y1 is N.

6. A compound of any one of claims 1-5, or a pharmaceutically acceptable salt or astereoisomer thereof, wherein R3and R5are Cl; R4, and R6are H, q is 1, p is 1 and wherein theheteroaryl groupRaa and Ra are as defined in claim 1.

7. A compound of any one of claims 1-6, wherein Rcc is H and Rc is selected from:

8. A compound of any one of claims 1-7, wherein Raais H and Rais selected from:

9. A compound of claim 1, wherein Y2 and Y3 are C, Y1 is N, R7 is MeO, R3 and R5 are Cl; R4, and R6 are H, q is 1, p is 1, Rcc is H, Rc is C1-6 alkyl substituted with Rd, wherein Rd is ORe, and Re is H, Raa is H, Ra is C1-6 alkyl substituted with Rd, wherein Rd is ORe, and and Re is H.

10. A compound of claim 1, wherein Y2and Y3are C, Y1is N, R7is methoxy (MeO), ethoxy (OEt) or isopropoxy (PriO), R3and R5are Cl; R4and R6are H, q is 1, p is 1, the heteroaryl groupRcc is H and Rc is selected from:

11. A compound of claim 1 selected from: 2-(((2',2''-dichloro-3''-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)- [1,1':3',1''-terphenyl]-4-yl)methyl)amino)ethan-1-ol (S)-1-(((6-(2,2'-dichloro-3'-(2-((((S)-2-hydroxypropyl)amino)methyl)-[1,2,4]triazolo[1,5- a]pyridin-7-yl)-[1,1'-biphenyl]-3-yl)-2-methoxypyridin-3-yl)methyl)amino)propan-2-ol;3-(((6-(2,2'-dichloro-3'-(2-(((3-hydroxypropyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7- yl)-[1,1'-biphenyl]-3-yl)-2-methoxypyridin-3-yl)methyl)amino)propan-1-ol; (R)-1-(((6-(2,2'-dichloro-3'-(2-((((R)-2-hydroxypropyl)amino)methyl)-[1,2,4]triazolo[1,5- a]pyridin-7-yl)-[1,1'-biphenyl]-3-yl)-2-methoxypyridin-3-yl)methyl)amino)propan-2-ol; N-(2-(((7-(3'-(5-(((2-acetamidoethyl)amino)methyl)-6-methoxypyridin-2-yl)-2,2'-dichloro- [1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)ethyl)acetamide; 2-(((6-(2,2'-dichloro-3'-(2-(((1-hydroxy-2-methylpropan-2-yl)amino)methyl)- [1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1'-biphenyl]-3-yl)-2-methoxypyridin-3-yl)methyl)amino)- 2-methylpropan-1-ol; 2-(((6-(2,2'-dichloro-3'-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)- [1,1'-biphenyl]-3-yl)-2-isopropoxypyridin-3-yl)methyl)amino)ethan-1-ol. 2-(((6-(2,2'-dichloro-3'-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)- [1,1'-biphenyl]-3-yl)-2-ethoxypyridin-3-yl)methyl)amino)ethan-1-ol.

12. A pharmaceutical composition comprising a compound of any one of claims 1-11, or apharmaceutically acceptable salt or a stereoisomer thereof, and one or more pharmaceutically acceptable excipient or carrier.

13. A compound of any one of claims 1-11, or a pharmaceutically acceptable salt or astereoisomer thereof, or a composition of claim 12, for use in a method of treating cancer.

14. A compound of any one of claims 1-11, or a pharmaceutically acceptable salt or astereoisomer thereof, or a composition of claim 12, for use in a method of treating an infection, preferably wherein the infection is a viral, or bacterial or a fungal infection.

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