HETEROCYCLIC AMIDE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING IT AND ITS USE IN THE MANUFACTURE OF A MEDICINAL PRODUCT

Abstract

Claim 1: A heterocyclic amide compound characterized in that it is (E)-1-(4-(5-carbamoyl-2-(1-ethyl-3-methyl-1H-pyrazol-5-carboxamido)-7-(3-morpholinopropoxy)-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)-2-(1-ethyl-3-methyl-1H-pyrazol-5-carboxamido)-7-methoxy-1H-benzo[d]imidazol-5-carboxamide having the structure of formula (1), or a tautomer thereof, or a pharmaceutically acceptable salt thereof, or a hydrate thereof.

Description

HETEROCYCLIC AMIDE COMPOUND, PHARMACEUTICAL COMPOSITION THAT INCLUDES IT AND ITS USE FOR THE MANUFACTURE OF A MEDICINAL PRODUCT Related request This application claims the benefit of priority over US Provisional Application No. 62 / 319358, filed on April 7, 2016, US Provisional Application No. 62 / 461301, filed on February 21 2017, and United States Provisional Application No. 62 / 461975, filed on February 22, 2017, the entire contents of which are incorporated herein by reference. field of invention The present invention relates to heterocyclic amides that are useful as modulators of transmembrane protein 173 (TMEM173), which is also known as STING (Stimulator of Interferon Genes), and to methods for producing and using the same. Background of the invention Vertebrates are constantly threatened by the invasion of microorganisms and have developed immune defense mechanisms throughout their evolution to eliminate infectious pathogens. In mammals, this immune system comprises two branches; innate immunity and adaptive immunity. The innate immune system is the first line of defense that is initiated by Pattern Recognition Receptors (PRRs) that detect pathogen ligands as well as damage associated with molecular patterns (Takeucho O. et al, Cell, 2010:140, 805-820). An increasing number of these receptors have been identified, including Toll-like receptors (TLR), C-type lectin receptors, retinoic acid-inducible gene I-type receptors (RIGI), and NOD-like receptors (NLR). and also double-stranded DNA sensors. Activation of PRRs results in the upregulation of genes involved in the inflammatory response, including type 1 interferons, proinflammatory atocins, and chemokines that suppress pathogen replication and facilitate adaptive immunity. The adapter protein STING (Stimulator of Interferon Genes), also known as TMEM 173, MPYS, MITA and ERIS, has been identified as a crucial signaling molecule in the innate immune response to cytosolic nucleic acids (Ishikawa H and Barber GN, Nature, 2008: 455, 674-678; Activation of STING results in the upregulation of IRF3 and NFkB pathways leading to the induction of interferon-β and other attocins. STING is critical for responses to cytosolic DNA of pathogen or host origin, and to rare nucleic acids called cyclic dinucleotides (CDN). IF-2019-16742483-APN-ANP#INPI 1 Page 1 of 402 CDNs were first identified as secondary bacterial messengers responsible for the control of numerous responses in the prokaryotic cell. Bacterial CDNs, such as c-di-GMP, are symmetrical molecules characterized by two 3',5' phosphodiester bonds. Direct activation of STING by bacterial CDNs has recently been confirmed by X-ray crystallography (Burdette D L and Vance R E, Nature Immunology, 2013:14, 19-26). Consequently, CDNs and their analogues have attracted interest as potential vaccine adjuvants (Libanova R. etal, Microbial Biotechnology 2012:5,168-176; WD2007 / 054279, W02005 / 087238). More recently, the response to cytosolic DNA has been elucidated and shown to involve the generation, by an enzyme called cyclic GMP-AMP synthase (cGAS, formerly known as C6orfl50 or MB21D1), of a novel CDN signaling molecule. mammalian cell identified as cGAMP, which then activates STING. Unlike bacterial CDNs, cGAMP is an asymmetric molecule characterized by its mixed 2',5' and 3',5' phosphodiester bonds. (Gao P etal, Cell, 2013:153,1094-1107). Likewise, the interaction of cGAMP (II) with STING has been demonstrated by X-ray crystallography (Cai X etal, Molecular Cell, 2014: 54, 289-296). Originally, interferon was described as a substance that could protect cells against viral infection (Isaacs and Lindemann, J. Virus Interference. Proc. R. Soc. Lon. Ser. B. Bioi. Sci. 1957:147, 258-267). In humans, type I interferons are a family of related proteins encoded by genes on chromosome 9 and encoding at least 13 isoforms of interferon alpha (IFNa) and one isoform of interferon beta (ΙΡΝβ). Recombinant IFNa was the first biological therapeutic agent and has become an important therapy for viral infections and cancer. As well as their direct antiviral activity in cells, interferons are known to be potent modulators of the immune response, acting on the cells of the immune system. The administration of a small molecule compound, which could modulate the innate immune response, including the activation or inhibition of the production of type I interferon and other cytokines, could be an important strategy for the IF-2019-16742483-APN-ANP#INPI2 Page 2 of 402 treatment or prevention of human diseases, including viral infections and autoimmune diseases. This type of immunomodulatory strategy has the potential to identify compounds that may be useful not only in innate immunity for infectious diseases, but also for cancer (Zitvogei, L, et a!., Nature Reviews Immunology, 201515(7), p405 -414), allergic diseases (MoisanJ. et al, Am. J. Physiol. Lung Cell Mol. Physiol., 2006:290, L987-995), neurodegenerative diseases, such as amyotrophic lateral sclerosis and multiple sclerosis {Lemos, H. et al, J. ImmunoL, 2014: 192(12), 5571-8; Cirulli, E. etaL, Science, 2015:347(6229), 1436-41; Freischmidt, A., etaL, Nat. Neurosci., 18(5), 631-6), other inflammatory conditions, such as irritable bowel disease (Rakoff-Nahoum S, Cell., 2004, 23,118(2): 229 -41), and as adjuvants for vaccines (Persing et ai. Trends Microbio!. 2002:10(10 Supi), S32-7y Dubensky et aL, Therapeutic Advances in Vaccines, published online September 5, 2013). STING is essential for host antimicrobial defense, including protection against a number of DNA and RNA viruses and bacteria (reviewed in Barber et al. Nat. Rev. ImmunoL 2015:15(2): 87-103, Ma and Damania , Cell Host & Microbe, 2016:19(2) ISO158). The Herpesviridae, Fiaviviridae, Coronaviridae, PapiHomaviridae, Adenoviridae, Hepadnaviridae, ortho- and paramyxoviridae, and rhabdoviridae have evolved mechanisms to inhibit STING-mediated type I interferon production and escape host immune control {Hoim et al., Nat Comm . 2016: 7:10680; Ma et al, PNAS 2015:112(31) E4306-E4315; Wu etai, Cell Host Microbe 2015:18(3) 333-44; Liu et al, J Virol 2016: 90(20) 9406-19; Chen et L, Protein Cell2014:5(5) 369-81; Lau etai, Science 2013: 350(6260) 568-71; Ding et al, J Hepatol 2013:59(1) 52-8; Nitta et al, Hepatology 2013 57(1) 46-58; Sun etai, PloS One 2012: 7(2) e30802; Aguirre etai, PioSPathog 2012: 8(10) el002934; Ishikawa etai, Nature2009: 461(7265) 788-92). Therefore, small molecule inactivation of STING could be beneficial for the treatment of these infectious diseases. In contrast, increased and prolonged production of type I IFN is associated with a number of chronic infections, including Mycobacteria (Collins et al, Cell Host Microbe 2015:17(6) 820-8); Wassermann etai., Cell Host Microbe 2015:17(6) 799-810; Watson et ai., Cell Host Microbe 2015:17(6) 811-9), Francisceiia {Storek et aL, J Immunol. 2015:194(7) 3236-45; Jin et al, J ImmunoL 2011:187(5) 2595-60Í), Chlamydia {Prantner et al, J Immunol 2010:184(5) 2551-60; Plasmodium {Sharma etai., Immunity 2011:35(2) 194-207. and HIV {Herzner et alL, Nat Immunol 201516(10) 1025-33; Gao et L, Science 2013:341(6148) 903-6. Similarly, excess production of type I interferon is observed among patients with complex forms of autoimmune diseases. We hypothesize that inhibition of STING results in a reduction in disease-driving type I interferon. IF-2019-16742483-APN-ANP#INPI3 Page 3 of 402 autoimmune disease is supported by genetic evidence in humans and by animal studies {Crow YJ, et al., Nat. Genet. 2006; 38(8) 38917-920, Stetson DB, et al., Cell 2008; 134587-598). Therefore, STING inhibitors provide a treatment for patients with chronic production of type I interferon and proinflammatory cytokines with infections or complex autoimmune diseases. Allergic diseases are associated with a Th2-biased immune response to allergens. Th2 responses are associated with increased levels of IgE, which, through their effects on mast cells, promote hypersensitivity to allergens, resulting in the symptoms observed, for example, in allergic rhinitis and asthma. In healthy individuals, the immune response to allergens is more balanced, with mixed Th2 / Th2 and regulatory T cell response. Induction of type I interferons has been shown to result in the reduction of Th2-type cytokines in the local environment and promote Thl / Treg responses. In this context, the induction of type I interferons through, for example, the activation of STING, may offer a benefit in the treatment of allergic diseases, such as asthma and allergic rhinitis {Huber J.P. et al J Immunol 2010: 185, 813-817). Compounds that bind STING and act as agonists have been shown to induce type I interferons and other cytokines when incubated with human PBMCs. Compounds that induce human interferons may be useful in the treatment of various disorders, for example, the treatment of allergic diseases and other inflammatory conditions, for example, allergic rhinitis and asthma, the treatment of infectious diseases, neurodegenerative disease, precancerous syndromes and cancer. , and may also be useful as an immunogenic composition or adjuvants for vaccines. Compounds that bind STING can act as antagonists and could be useful in the treatment, for example, of autoimmune diseases. It is anticipated that targeting STING with activating or inhibiting agents may be a promising strategy to treat diseases and conditions in which modulation of the type 1 IFN pathway is beneficial, including inflammatory, allergic and autoimmune diseases, infections, cancer, precancerous syndromes and as immunogenic composition or adjuvants for vaccines. Skin cancers and various viral skin infections involve an immune-privileged environment and activation of the local immune response to lesions may be a topical therapeutic strategy. STING agonists can be used to treat viral warts, superficial skin cancers, and premalignant actinic keratoses. Through a dual mechanism of action, STING activation (e.g., through microneedle patch delivery or a topical formulation) can be used to directly control HPV through the production of antiviral type I interferon and indirectly enhancing the IF-2019-16742483-APN-ANP#INPI4 Page 4 of 402 adaptive immune response downstream of innate immune activation. STING agonists can activate the innate immune response in the lesion and drive the anti-HPV T cell response. Recent evidence has indicated that spontaneous activation of the STING pathway in tumor-resident dendritic cells leads to type I IFN production and adaptive immune responses against tumors. Furthermore, activation of this pathway in antigen-presenting cells (APCs) in the tumor microenvironment drives subsequent priming of T cells against tumor-associated antigens. Corrales and Gajewski, Clin Cancer Res; 21(21); 4774-9, 2015. International Patent Applications WO2014 / 093936, WO2014 / 189805, WO2013 / 185052, U.S.2014 / 0341976, WO 2015 / 077354, PCT / EP2015 / 062281 and GB 1501462.4 disclose certain cyclic dinucleotides and their use to induce an immune response through the activation of STING. The compounds of the present invention modulate the activity of STING, and therefore, may provide a beneficial therapeutic impact in the treatment of diseases, disorders and / or conditions in which the modulation of STING (Stimulator of Interferon Genes) is beneficial. , for example, for inflammatory, allergic and autoimmune diseases, infectious diseases, cancer, precancerous syndromes and as adjuvants for vaccines. DIGEST OF THE INVENTION The invention relates to a compound according to the formula (I-N): IF-2019-16742483-APN-ANP#INPI5 Page 5 of 402 R4 where: q is 0 or 1; r is 0 or 1; s is 0 or 1; where q + r + s = 1 or 2; when q is 0, RA1 and RA2 are each independently H, halogen, hydroxy, -0P(O)(OH)2, -Ο-Ρ(Ο)(^Π)2, -N(Re)(Rf), -CO2Rf, -N(Rf)CORb, -N(R9)SO2(Ci-C4 alkyl)-N(Re)( Rf), -N(R9)CO(Ci-C4 alkyl)-N(Rb)(Rf), (Ci-C6 alkyl) optionally substituted, (Cj-CeJoxy- alkyl optionally substituted, (Ci-C^amino-alkyl) optionally substituted, and (Ci-C6 alkyl)(optionally substituted CrC^alkyl)amino-, wherein the (Ci-C6 alkyl) of said (CrC6 alkyl) optionally substituted, (Ci-Ce alkyl)oxy- optionally substituted, (alkyl optionally substituted Ci-Ce)amino- and (optionally substituted Ci-C6 alkyl)(optionally substituted Ci-C^alkylamino-) is optionally substituted with 1-4 substituents each independently selected from hydroxy, -O-P(O)(OH)2, -Ο-Ρ(Ο)(^π)2, CpCr alkoxy, -N(Re)(Rf), -CO2(Rf), -CON(Re)(Rf), optionally substituted phenyl, optionally substituted 5-6-membered heterocycloalkyl and an optionally substituted 5-6-membered heteroaryl group, wherein said optionally substituted phenyl, 5-6 membered heterocycloalkyl or 5-6 membered heteroaryl is optionally IF-2019-16742483-APN-ANP#INPI6 Page 6 of 402 substituted with 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -O-PÍOjíR'R11)^ amino, (Ci-C6 alkyl)amino-, (alkyl Ci-C6)(CrC6 alkyl)amino-, -(Ci-Cej-NHz alkyl, halo(CrC6 alkyl), hydroxy-(CrC» alkyl)-, -(Ci-C4 alkyl)-O-P(O)(OH) 2, -(alkyl Ci-Qj-O-PtOXR'R11)^ halo(alkoxy¡ Ci-C,)-, alkoxy CrC4-, hydroxy-(alkoxy C2-C})-, -(alkoxy C2-Q)-O-P(O)(OH)2, -(alkoxy (Ζ2<4)-Ο-Ρ(Ο)(^Π)2, -alkyl Ci-CHalkoxy Ci-C») or alkoxy Ci-CXalkoxy CrQ)-; when r is 0, RB1 and RB2 are each independently optionally substituted, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-10 membered heteroaryl, wherein said optionally substituted Ci-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, C3-cycloalkyl C6optionally substituted, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-10 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, nitro , -Rc, -OH, -O-P(O)(OH)2, -Ο-Ρ(Ο)(^Π)2, -ORC, -NH2, -NRCRC, -NRcRd, -OCORC, -CO2H, -CO2Rc , -SORc, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc; when s is 0, RC1 is H, halogen, or Ci-q alkyl and RC2 is optionally substituted CrQ alkyl, wherein said optionally substituted Ci-C4 alkyl group is optionally substituted with a substituent selected from -ORC, -NRcRd, -CO2Rc, -CONRcRd , -SO2NRcRd, and -OCONRcRd; when q is 1, RA1 and RA2 are each independently -CH2-, -NRe-, or -O-, and A, taken together with RA1 and RA2, forms a linking group, where A is -halo(Ci-C12 alkyl)- , -Cx-Ci2-alkyl- optionally substituted, C2-Ci2-alkenyl- optionally substituted, C2-Ci2-alkynyl- optionally substituted, -Ci-Cg-O-alkyl Ci-Ce- optionally substituted, -CrC6-alkyl-NRa-CrCg-alkyl- optionally substituted, -Ci-C6-alkyl-(C3-C6 cycloalkyl)-Ci-C6-alkyl- optionally substituted, -Ci-C6-alkyl-phenyl- alkyl CrQj- optionally substituted, -CrC6-alkyl-(4-6-membered heterocycloalkyl)-optionally substituted CrC6-alkyl, or -optionally substituted -CrC6-alkyl-(5-6-membered heteroaryl)-CrCg-alkyl, wherein the alkyl moiety of said -Ci-Ci2-alkyl - optionally substituted, alkenyl IF-2019-16742483-APN-ANP#INPI 7 Page 7 of 402 C2-Ci2- optionally substituted, C2-Ci2-alkynyl optionally substituted, -CrC6-alkyl-O-Ci-C6-alkyl- optionally substituted, -Ci-C6-alkyl-NRa-Cj-Cg-alkyl- optionally substituted, -CrCg-alkyl-( C3-C6 cycloalkyl)-CrC6-alkyl- optionally substituted, -CrCg-alkyl-phenyl-Ci-C6-alkyl- optionally substituted, -CrCg-alkyl-(4-6-membered heterocycloalkyl)-alkyl optionally substituted Ci-Cg-, or -optionally substituted -Ci-Cg-alkyl-(5-6 membered heteroaryl)-optionally substituted Ci-C6-alkyl is optionally substituted by 1-4 substituents each independently selected from halogen, halo(Ci-alkyl) C4), -OH, -O-P(O)(OH)2, -O-P(O)(R'Rn)2, -ORC, -NH2, -NRcRd, -OCORc, -CO2H, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and - NRdSO2Rc, and the C3-C6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said optionally substituted -CrC6 alkyl-(C3-Cg cycloalkyl)-Ci-Cg alkyl-, -Ci-C6 alkyl- optionally substituted phenyl-Ci-Cg-alkyl, -optionally substituted -Ci-C6-alkyl-(4-6-membered heterocycloalkyl)-optionally substituted-Ci-Cg-alkyl, or -optionally substituted-Ci-C6-alkyl-(5-6-membered heteroaryl)-alkyl Optionally substituted Cj-Cg- is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -O-R(O)(R!Rn)2, amino, (alkyl Ci -C4)amino-, (Cj-qAlkylCi-Qamino-alkyl, CrC4 alkyl, halo(CrC4 alkyl), halo(Ci-C alkoxy)-, Cj-C alkoxy-, hydroxy-(Ci-alkoxy- C4)-, -(C1-C4 alkoxyl)-O-P(O)(OH)2, -(Ci-C^-O-PCOXR'R11 alkoxyl);" and Ci-C4 alkoxy-(Ci-Ci alkoxy) -; when r is 1, RB1 and RB2 are each independently -CH2-, and B, taken together with RB1 and Rb2, forms a linking group, where B is a bond or B is -halo(Ci-Cio alkyl)-, -Ci alkyl -Cw optionally substituted, C2-Ci0-alkenyl optionally substituted, C2-Ci0-alkynyl optionally substituted, -CpCg-O-alkyl Ci-Cg- optionally substituted, -Ci-C6-alkyl-NRa-Cj-Cg-alkyl- optionally substituted, C3-C6 cycloalkyl optionally substituted, phenyl optionally substituted, 4-6 membered heterocycloalkyl optionally substituted, 5-6 membered heteroaryl optionally substituted , -Ci-C4alkyl-(C3-Cg cycloalkyl)-Cj-C»-alkyl- optionally substituted, -Cy-Q-alkyl-phenyl-Ci-C4-alkyl- optionally substituted, -4-6-membered Ci-Crtheterocycloalkyl) -optionally substituted CrCr alkyl, or -optionally substituted -Ci-CXalkylheteroarylj-optionally substituted Ci-Cp alkyl, wherein the alkyl moiety of said -optionally substituted -Cj-Cio*alkyl, optionally substituted C2-Ciq-alkenyl, alkynyl C2-Ciq- optionally substituted, -CrCg-O-alkylCi-C6-alkyl- optionally substituted, -CrC6-alkyl-NRa-alkyl IF-2019-16742483-APN-ANP#INPI8 Page 8 of 402 Ci-C6- optionally substituted, -alkyl Ci-CAcycloalkyl C3-C6)-alkyl C1-C4- optionally substituted, -alkylCy-Crphenyl-C1-C4alkyl- optionally substituted, -alkylCy-CXheterocycloalkyl4-6 membered)-alkyl C1-C4- optionally substituted, or -CrC alkyl|-(5-6 membered heteroaryl-C1-C4 alkyl)- optionally substituted is optionally substituted with 1 or 2 substituents each independently selected from halogen, halo(CrC alkyl,) , -OH, -O-P(O)(OH)2, -O-P(O)(RiRn)2, -ORC, -NH2i -NRcRd, -OCORc, -CO2H, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc, and the moiety C3-C6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl or 5-6 heteroaryl members of said optionally substituted C3-C6 cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, -optionally substituted C1-C4 alkyl, - Ci-Clj-alkyl-phenyl-C1-C4-alkyl- optionally substituted, -CrCr-alkyl(4-6-membered Cheterocycloalkyl)-alkyl C1-C4- optionally substituted, or -alkylCrCX5-6-memberedheteroaryl)-optionally substituted C1-C4-alkyl is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH) 2, O-P / OXR'r'A, amino, (CrCOamino-alkyl, (Ci-C4 alkyl)(Ci-COamino-alkyl, C1-C4 alkyl, halo(C1-C4 alkyl), halo(C1-C4 alkoxy )-, C1-C4-alkoxy-, hydroxy-(CrCj alkoxy)-, (CrC alkoxy») O-P(O)(OH)2, -(CrGO-O-PIOXR'R11 alkoxy);", and Cj-alkoxy- CKalkoxy Ci-C,)-; when s is 1, RC1 and RC2 are each independently -CH2-, and C, taken together with RC1 and RC2, forms a linker group, where C is -halo(Ci-Ci2 alkyl)-, -Cj-Ci2 alkyl- optionally substituted , optionally substituted C2-Ci2-alkenyl, optionally substituted C2-CJ2-alkynyl, -optionally substituted -CrC6-O-alkyl-CrC6-alkyl, -optionally substituted -Ci-C6-alkyl-NRa-optionally substituted CrC6-alkyl, -CrC6-alkyl-(C3-cycloalkyl -C6)-alkyl Ci-Cg- optionally substituted, -alkyl CrCg-phenyl-alkyl CrC6- optionally substituted, -alkyl CrCg-(4-6 membered heterocycloalkylj-alkyl CrC6- optionally substituted, or -alkyl CrCg-(5-6 membered heteroaryl)-alkyl Cx-Cg- optionally substituted, wherein the alkyl moiety of said -CrCi2-alkyl- optionally substituted, C2-C12-alkenyl- optionally substituted, C2-Ci2-alkynyl- optionally substituted, -CrCg-O-alkyl-Q-Cg-alkyl- optionally substituted, -Ci-Cg-NRa-alkyl-Ci-alkyl- Cg- optionally substituted, -alkyl CrCg-(C3-C6 cycloalkyl)-alkyl IF-2019-16742483-APN-ANP#INPI 9 Page 9 of 402 Ci-C6- optionally substituted, -Cj-C6 alkyl-phenyI-Ci-C6-alkyl optionally substituted, -CrC6 alkyl-(4-6-membered heterocycloalkyl)-alkyl Optionally substituted Ci-C6-, or -CrC6-alkyl-(5-6-membered heteroaryl)-optionally substituted CrC6-alkyl is optionally substituted with 1 or 2 substituents each independently selected from halogen, halo(Ci-C4 alkyl), - OH, -O-P(O)(OH)2, -O-R(O)(R'Rn)2, -ORC, -NH2, -NRcRd, -OCORc, -CO2H, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and - NRdSO2Rc, and the C3-C6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said optionally substituted -Ci-C6 alkyl-(C3-Cg cycloalkyl)-Ci-Cg alkyl-, -Cj alkyl- Optionally substituted Ce-phenyl-Ci-C6-alkyl, -Cj-Ce-alkyl(4-6 membered Cheterocycloalkyl)-optionally substituted Ci-C6-alkyl, or -Ci-C6-alkyl-(5-6 membered heteroaryl) )-optionally substituted Ci-C6-alkyl is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -O-PCOXR'R11)?, amino, (Ci-alkyl -COamino-, (Ci-C alkyl), (Ci-C alkyl^amino-, C1-C4 alkyl, halo(C1-C4 alkyl), halo(C1-C4 alkoxy)-, C1-C4 alkoxy-, hydroxy -(alkoxy¡ 0,-0,)-, -(alkoxy C2-C,)-0P(O)(OH)2, -(alkoxy 02-0,)-0-Ρ(0)(^Π)2 , and alkoxy O-C,-(alkoxy¡ O-C,)-; R3 and R5 are each independently -CON(Rd)(Rf), or one of R3 and R5 is -CON(Rd)(Rf), and the other of R3 and R5 is H, COOH or -CO2(RC); R4 and R6 are each independently selected from H, halogen, halo(O-C6 alkyl), halo(O-C6 alkoxy)-, hydroxy, -O-P(O)(OH)2, -0Ρ(0)(^π) 2, -NH2, -NRcRc, -NRcRd, -CORc, -C02Rc, -N(Rd)CORc, -N(Rd)SO2Rc, -N(R9)SO2(Ci-C2 alkyl)-N(Rh)(Rf), -N(R9)CO(Ci-C2 alkyl)-N(Rh)(Rf), ( optionally substituted Ci-Ce alkyl, (optionally substituted CrCgjoxy alkyl, optionally substituted (Ci-C6 alkyl)amino, and optionally substituted (Ci-C6 alkyl)(CrCOamino alkyl), wherein the (O-C6 alkyl) of said (CrC6 alkyl) optionally substituted, (Ci-C6 alkyl)oxy- optionally substituted, (CrCejamino alkyl- optionally substituted and (Ci-C6 alkyl)(optionally substituted CpGOamino alkyl) is optionally substituted with 1-4 substituents each independently selected between -OH, -O-P(O)(OH)2, -0-Ρ(0)(^π)2,^ε, -NH2, -NRCRC, -NRcRd, -CO2H, -CO2Rc, -OCORc, -CO2H, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc , -NRdCO2Rc, -NRdSO2Rc, optionally substituted phenyl, 5-6 heterocycloalkyl IF-2019-16742483-APN-ANP#INPI10 Page 10 of 402 optionally substituted members and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl, 5-6 membered heterocycloalkyl or 5-6 membered heteroaryl is optionally substituted with 1-4 selected substituents each independently from halogen, hydroxy, -O-P(O)(OH)2, -O-PCOXlVR11^, amino, (Ci-COamino alkyl, (Ci-C4 alkyl)(CrC4 alkyl)amino-, C1-C4 alkyl, halo (C1-C4 alkyl), hydroxy-(C1-C4 alkyl)-, (Ci-C4 alkyl)-O-P(O)(OH)2, -(Ci-CO-O-PIOXR1^ alkoxy, halo(CrC4 alkoxy )-, CrCr alkoxy, hydroxy-(C2-C4 alkoxy)-, -(C2-C4 alkoxy)-O-P(O)(OH)2, -(alkoxy CrCO-O-PIOXR'RHh, alkoxy Ci-C4-(alkoxy¡ CpC,)-, -CORd, -CON(Rd)(Rf), and -CO2Rd; R14 is optionally substituted C1-C4 alkyl, wherein said optionally substituted Ci-Ci alkyl is optionally substituted with a substituent selected from -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; R16is H, halogen, or CrG alkyl; R15 and R17 are each independently H, cyclopropyl, or Ci-Ct alkyl; Raes H, -Rc, -CORc, -CO2H, -CO2Rc, -SORC, -SO2RC, -CONH2, -CONRcRd, -SO2NH2, or -SO2NRcRd; each Rbes independently C1-C4 alkyl, halo(CrC4 alkyl), -(CrC4 alkyl)-OH, -(alkyl Ci-CO-O-PIOXOHh, -(alkoxy Ci-Cjj-O-PIOjíR'R1^, -(alkyl Ci-Q-OXalkyl Cj-C,), -(alkyl Ci-CO-N^XRf) , -(Ci-Q-O-CCXC1-C4alkyl), or -(Ci-C,alkyl)-CO-O-(CrC,alkyl); each Rces independently alkyl CrC^, halo(alkyl Cj-Q), -(alkyl Ci-CO-OH, -(alkyl Ci-Q-O-PIOXOHh, -(alkyl Ci-CO-O-PtOXR'RHh, -(alkyl CrCQ-O-alkyl CpC,), -(alkyl CpCO-N^XR'), -(alkyl Ci-CQ-O-CCXalkyl Ci-C» ), -(Cj-CO-CO-OXalkylCi-CQalkyl, optionally substituted C3-C6cycloalkyl, optionally substituted phenyl, optionally substituted 4-6-membered heterocycloalkyl, optionally substituted 5-6-membered heteroaryl, 9-10-membered heteroaryl optionally substituted, -Ci-C^alkyl-C3-C6cycloalkyl optionally substituted, -Cj-alkyl-Crphenyl optionally substituted, -Ci-C4alkyl-4-6 membered heterocycloalkyl optionally substituted, -5-6 membered Ci-Crheteroaryl alkyl optionally substituted substituted, or - optionally substituted 9-10 membered CrCrheteroaryl alkyl, wherein the C3-C6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl or 9-10 membered heteroaryl moiety of said C3-Ce cycloalkyl optionally substituted, optionally substituted phenyl, optionally substituted 4-6-membered heterocycloalkyl, optionally substituted 5-6-membered heteroaryl, optionally substituted 9-10-membered heteroaryl, -alkyl IF-2019-16742483-APN-ANP#INPI11 Page 11 of 402 optionally substituted Ci-C^-C3-C6 cycloalkyl, -optionally substituted Ci-C4 alkylphenyl, -optionally substituted 4-6 membered Ci-Crheterocycloalkyl, -optionally substituted 5-6 membered Ci-Crheteroaryl alkyl, or - optionally substituted 9-10 membered alkyl Ci-Qrheteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -O-PtOXR'RHh, amino, -(alkyl Ci-C4)NH2, (alkyl enjamino-, (alkyl CrC4)(alkyl Ci-C4)amino-, alkyl Ci-Q, halo(alkyl C4-C4), halo(alkoxy Ci-Cj)-, alkoxy CrCp , hydroxy-(alkoxy CrC,)-, -(alkoxy C2-C4)-O-P(O)(OH)2, -(alkoxy σ2-Οι)-0-Ρ(0)(^π)2, alkoxy CrC4- (alkoxy Cj-C,)-, -CORd, -CON(Rd)(Rf), and -CO2Rd; each Rdes independently H or CpC alkyl,; each Rees independently H, (CrCj alkyl), -CO(Ci-CO alkyl, -OCO(alkyl Ci-C,), -CO2(CpCO alkyl, -(Ci-C4 alkyl)NH2, -(CrC4 alkyl) C1-C4 alkoxy, -CO-(5-6 membered heterocycloalkyl optionally substituted), -CO(Ci-C4 alkyl)-(5-6 membered heterocycloalkyl optionally substituted), -CO(optionally substituted 5-6-membered heteroaryl), -CO(optionally substituted 5-6-membered alkylheteroaryl), wherein the optionally substituted 5-6-membered heterocycloalkyl or the 5-6-membered heteroaryl optionally substituted members are optionally substituted with 1-4 substituents independently selected from halogen, hydroxy, -OP(O)(OH)2, -O-P(O)(RiRii)2, amino, (Ci-C4 alkyl)amino-, ( Ci-C^XalkylCj-Cljamino-alkyl, C1-C4 alkyl, halo(C1-C4 alkyl), halo(CrC alkoxy)-, C1-C4 alkoxy-, hydroxy-(C2-C4 alkoxy)-, - (alkoxy Q-C4) O-P(O)(OH)2, -(CrCO-O-PÍOXR’RHh alkoxy, C1-C4 alkoxy Ci-CXalkoxy)-, -CORd, -CON(Rd)(Rf), and -CO2Rd; each Rfes independently H or (C1-C4 alkyl); R9 and Rh are each independently H or (Ci-Q alkyl) or R9 and Rh, taken together with the atom or atoms through which they are connected, form a 5-6 membered ring; and each occurrence of R1 and Rnes independently (Ci-C6 alkyl)ox¡-; or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. References herein to compounds of formula (I-N), (I-P) or (I), and salts thereof, should be understood to encompass compounds of formula (I-N), (I-P) or (I), in the form of free bases, or as salts thereof, for example, in the form of salts IF-2019-16742483-APN-ANP#INPI12 Page 12 of 402 pharmaceutically acceptable thereof. Therefore, in one embodiment, the invention relates to compounds of formula (I-N), (I-P) or (I), in the form of their free base. In another embodiment, the invention relates to compounds of formula (I-N), (I-P) ο (I), and salts thereof. In a further embodiment, the invention relates to compounds of formula (I-N), (I-P)ο (I), and pharmaceutically acceptable salts thereof. Compounds according to the formula (I-N), (I-P) or (I), or their salts, in particular pharmaceutically acceptable salts thereof, are STING modulators. Accordingly, the present invention provides a compound of formula (I-N), (I-P) or (I) or a salt thereof, in particular a pharmaceutically acceptable salt thereof, for use in therapy. The present invention specifically provides the use of a compound of formula (I-N), (I-P)ο (I), or a pharmaceutically acceptable salt thereof, as an active therapeutic substance in the treatment of a STING-mediated disease or disorder, specifically, for use in the treatment of a disease mediated by STING agonism or antagonism. Likewise, the invention provides a compound of formula (I-N), (I-P)ο (I), or a salt thereof, in particular a pharmaceutically acceptable salt thereof, for use in the manufacture of a medicament for the treatment of a STING-mediated disease or disorder. The invention also relates to a method for modulating STING, said method comprising contacting a cell with a compound according to the formula (I-N), (I-P) or (I), or a salt, in particular a pharmaceutically acceptable salt thereof. . Furthermore, the invention relates to a method of treating a STING-mediated disease or disorder comprising administering a therapeutically effective amount of a compound according to formula (I-N), (I-P) or (I), or a salt, in particular a pharmaceutically acceptable salt thereof, to a patient (a human being or other mammal, in particular, a human being) in need thereof. Such STING-mediated diseases or disorders include inflammation, allergic and autoimmune diseases, infectious diseases, cancer, and precancerous syndromes. Furthermore, STING modulators may be useful as immunogenic composition or vaccine adjuvants. The present invention further relates to a pharmaceutical composition comprising a compound according to the formula (I-N), (I-P) or (I), or a salt, in particular a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In particular, the present invention relates to a pharmaceutical composition for the treatment of a STING-mediated disease or disorder, where the composition comprises a compound according to the formula (I-N), (I-P) or (I), or a salt, in particularly a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. IF-2019-16742483-APN-ANP#INPI13 Page 13 of 402 Detailed description of the request According to one aspect of the present invention, the present invention relates to compounds of formula (I-N) where: q is 0 or 1; r is 0 or 1; s is 0 or 1; where q + r + s = 1 or 2; when q is 0, RA1 and RA2 are each independently H, halogen, hydroxy, -0P(O)(OH)2, -Ο-Ρ(Ο)(^Π)2, -N(Re)(Rf), -CO2Rf, -N(Rf)CORb, -N(R9)SO2(Ci-C4 alkyl)-N(Re )(Rf), -N(R9)CO(Ci-C4 alkyl)-N(Rh)(Rf), (Ci-C6 alkyl) optionally substituted, (CrC6 alkyl)ox¡- optionally substituted, (CrCgjamino alkyl- optionally substituted, and (Ci-C6 alkyl)(optionally substituted Ci-C^amino-alkyl, wherein the (Ci-C6 alkyl) of said optionally substituted (Ci-C6 alkyl), (optionally substituted Ci-Cgjoxy-alkyl, ( optionally substituted Ci-CéJamino alkyl- and (optionally substituted Ci-C6 alkyl)(optionally substituted Ci-COamino alkyl- is optionally substituted with 1-4 substituents each independently selected from hydroxy, -O-P(O)(OH)2, -Ο- Ρ(Ο)(^Βπ)2, alkoxy C1-C4-, -N(Re)(Rf), -CO2(Rf), -CON(Re)(Rf), optionally substituted phenyl, IF-2019-16742483-APN-ANP#INPI 14 Page 14 of 402 optionally substituted 5-6 membered heterocycloalkyl and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl, 5-6 membered heterocycloalkyl or 5-6 membered heteroaryl is optionally substituted with 1- 4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -O-PIOXlVR11^, amino, (Ci-C6 alkyl)amino-, (Ci-C6 alkyl)(CrC6 alkyl)amino- , -(Ci-C6 alkyl)-NH2, halo(Ci-C6 alkyl), hydroxy-(C1-C4 alkyl)-, -(Ci-C4 alkyl)-O-P(O)(OH)2, -(Ci alkyl -CO-O-PIOXR'R11);!, halo(C1-C4 alkoxy)-, CpCr alkoxy, hydroxy-(C2-C, alkoxy)-, -(C2-C4 alkoxy)-O-P(O)(OH )2, -(C2-C4 alkoxy)-O-P(O)(RiRii)2, -Ci-Cr alkyl(C1-C4 alkoxy) and Ci-C4 alkoxy-(C1-C4 alkoxy)-; when r is 0, RB1 and RB2 are each independently optionally substituted, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-10 membered heteroaryl, wherein said optionally substituted Ci-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, C3-cycloalkyl C6optionally substituted, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-10 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, nitro , -Rc, -OH, -O-P(O)(OH)2, -Ο-Ρ(ΟΧ^Π)2, -ORc, -NH2, -NRcRc, -NRcRd, -OCORc, -CO2H, -CO2Rc, - SORc, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc; when s is 0, RC1 is H, halogen, or C1-C4 alkyl and RC2 is optionally substituted C1-C4 alkyl, wherein said optionally substituted C1-C4 alkyl group is optionally substituted with a substituent selected from -ORC, -NRcRd, -CO2Rc , -CONRcRd, -SO2NRcRd, and -OCONRcRd; when q is 1, RA1 and RA2 are each independently -CH2-, -NRe-, or -O-, and A, taken together with RA1 and RA2, forms a linking group, where A is -halo(CrCi2 alkyl)-, - Ci-Ci2-alkyl- optionally substituted, C2-Ci2-alkyl- optionally substituted, C2-Ci2-alkyl- optionally substituted, -CrC6-alkyl-O-Ci-C6-alkyl- optionally substituted, -CrC6-NRa-alkyl-Ci-C6-alkyl- optionally substituted, -Ci-C6 alkyl-(C3-C6 cycloalkyl)-Ci-C6 alkyl- optionally substituted, -Ci-C6 alkyl-phenyl-Ci-Q alkyl- optionally substituted, -Ci-C6 alkyl-(heterocycloalkyl 4-6 IF-2019-16742483-APN-ANP#INPI15 Page 15 of 402 members)-optionally substituted Ci-C6-alkyl, or -optionally substituted -Ci-C6-alkyl-(5-6-membered heteroaryl)-optionally substituted Ci-C6-alkyl, wherein the alkyl moiety of said -Ci-alkyl- Ci2- optionally substituted, C2-C12 alkenyl- optionally substituted, C2-C12 alkynyl- optionally substituted, -Ci-C6-O alkyl-Cj-Cg alkyl- optionally substituted, -CrCg-NRa alkyl-Cj-Cg alkyl- optionally substituted , -Ci-C6 alkyl-(C3-C6 cycloalkyl)-CrCg alkyl- optionally substituted, -Ci-Cg alkyl-phenyl-Ci-Cg alkyl- optionally substituted, -Ci-C6 alkyl-(4-6 heterocycloalkyl members)-alkyl Ci-Cg- optionally substituted, or -alkyl Ci-Cg-(5-6 membered heteroaryl)-optionally substituted Ci-Cg-alkyl is optionally substituted by 1-4 substituents each independently selected from halogen, halo(C1 alkyl- C4), -OH, -O-P(O)(OH)2, -Ο-Ρ(ΟΧ^Π)2, -ORC, -NH2, -NRcRd, -OCORc, -CO2H, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and - NRdSO2Rc, and the C3-C6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said optionally substituted -Ci-Cg alkyl-(C3-Cg cycloalkyl)-Ci-C6 alkyl, - Ci-Cg alkyl-phenyl-optionally substituted Ci-C6 alkyl, -CrCg alkyl-(4-6 membered heterocycloalkyl)-optionally substituted CrCg alkyl, or -Ci-C6 alkyl-(5-6 membered heteroaryl)- optionally substituted Ci-C6- alkyl is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -O-PCOXR'R11^, amino, (alkyl CrCOamino-, ( Cj-CíX alkylCrC^amino-alkyl, C1-C4 alkyl, halo(C1-C4 alkyl), halo(C1-C4 alkoxy)-, C1-C4 alkoxy-, hydroxy-(C1-C4 alkoxy)-, - (Ci-C4 alkoxy)-O-P(O)(OH)2, -(C1-C4 alkoxy)-O-P(O)(RiRii)2 and CrCríalkoxy Cj-C»)-alkoxy; when r is 1, RB1 and RB2 are each independently -CH2-, and B, taken together with RB1 and Rb2, forms a linking group, where B is a bond or B is -halo(C1-C10 alkyl)-, -CrCi0 alkyl - optionally substituted, C2-Ci0-alkenyl optionally substituted, C2-Ci0-alkynyl optionally substituted, -Ci-Cg-O-alkyl Cj-Cg- optionally substituted, -alkyl Ci-Cg-NRa-alkyl CrCg- optionally substituted, C3-C6 cycloalkyl optionally substituted, phenyl optionally substituted, 4-6 membered heterocycloalkyl optionally substituted, 5-6 membered heteroaryl optionally substituted, - CrCrycycloalkyl (C3-C6 alkyl)-C1-C4 alkyl- optionally substituted, -Ci-CLj alkyl-phenyl-C1-C4 alkyl- optionally substituted, -Ci-C4 alkyl-(4-6 membered heterocycloalkylj-C1-C4 alkyl- optionally substituted, or -optionally substituted -Ci-C4-alkyl-(5-6-membered heteroaryl)-alkyl, IF-2019-16742483-APN-ANP#INPI16 Page 16 of 402 wherein the alkyl moiety of said -Ci-Cjo-alkyl- optionally substituted, C2-Cio-alkenyl optionally substituted, C2-Ci0-alkynyl- optionally substituted, -CrC6-O-alkylCpCg-alkyl- optionally substituted, -alkyl Ci-C6-NRa-Cj-Cg alkyl- optionally substituted, -Ci-C4 alkyl-(C3-C6 cycloalkyl)-C1-C4 alkyl- optionally substituted, -Ci-Cj alkyl-phenyl-C1-C4 alkyl- optionally substituted , -alkyl Ci-CK(4-6 membered heterocycloalkyl)-alkyl C1-C4- optionally substituted, or -Cj-alkyl-CK5-6-membered heteroaryl-C1-C4 alkyl)- optionally substituted is optionally substituted with 1 or 2 substituents each independently selected from halogen, halo(C1-C4 alkyl), -OH, -O-P(O)(OH)2, -O-PIOXR'R11^, -ORC, -NH2, -NRcRd, -OCORc, -CO2H, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd , -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc, and the C3-C6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl or 5-6 membered heteroaryl moiety of said optionally substituted C3-C6 cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, -Cj-CXalkylC3-Cgcycloalkyl)-optionally substituted C1-C4 alkyl, -Ci alkyl -C^-phenyl-alkyl Cj-Q- optionally substituted, -alkyl CrC4-(4-6-membered heterocycloalkyl)-alkyl C1-C4- optionally substituted, or -Ci-C4-alkyl-(5-6-membered heteroaryl)-optionally substituted C1-C4-alkyl is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, -O-P( O)(OH)2, O-PCOXR'R11^, amino, (alkyl examino-, (Ci-CíX alkylCi-C4alkyl)amino-, C1-C4 alkyl, halo(C1-C4 alkyl), halo(alkoxy C1-C4)-, C1-C4 alkoxy-, hydroxy-(C2-C4 alkoxy)-, (C2-C4 alkoxy) O-P(O)(OH)2, -(CrCO-O-PIOXRW'h alkoxy, and alkoxy C^Xalkoxy C1-C4)-; when s is 1, RC1 and RC2 are each independently -CH2-, and C, taken together with RC1 and RC2, forms a linker group, where C is -halo(Ci-Ci2 alkyl)-, -Ci-Ci2 alkyl- optionally substituted , C2-Cj2-alkenyl- optionally substituted, C2-Ci2-alkynyl- optionally substituted, -CpCg-O-alkyl-Ci-C6-alkyl- optionally substituted, -Ci-C6-alkyl-NRa-CrC6-alkyl- optionally substituted, -Ci-C6-alkyl -(C3-C6 cycloalkyl)-CrCg-alkyl- optionally substituted, -CrCg-alkyl-phenyl-alkyl Ci-C6- optionally substituted, -CrC6-alkyl-(4-6-membered heterocycloalkylj-optionally substituted CrC6-alkyl, or -optionally substituted -CrCg-alkyl-(5-6-membered heteroaryl)-Ci-Cg-alkyl, wherein alkyl moiety of said optionally substituted -Ci-Ci2-alkyl, alkenyl IF-2019-16742483-APN-ANP#INPI 17 Page 17 of 402 C2-C12- optionally substituted, C2-C12-alkynyl- optionally substituted, -CrC6-O-alkyl-Ci-C6-alkyl- optionally substituted, -Ci-C6-alkyl-NRa-Ci-C6-alkyl- optionally substituted, -Ci-C6-alkyl -(C3-C6 cycloalkyl)-alkyl Ci-C6- optionally substituted, -alkyl CrC6-phenyl-alkyl Ci-C6- optionally substituted, -alkyl CrCgX4-6 membered heterocycloalkyl)-alkyl optionally substituted Ci-C6-alkyl, or -optionally substituted Ci-C6-alkyl-(5-6-membered heteroaryl)-optionally substituted Ci-Ce-alkyl is optionally substituted with 1 or 2 substituents each independently selected from halogen, halo(C1-alkyl- C4), -OH, -O-P(O)(OH)2, -Ο-Ρ(ΟΧ^Π)2, -ORC, -NH2, -NRcRd, -OCORc, -CO2H, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd, -5Ο2ΝΗ2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and - NRdSO2Rc, and the C3-C6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said -CrC6 alkyl-(C3-Ce cycloalkyl)-optionally substituted Ci-C6 alkyl, -Ci-C6 alkyl- optionally substituted phenyl-Ci-C6-alkyl, -optionally substituted -Ci-C6-alkyl-(4-6-membered heterocycloalkyl)-optionally substituted-Ci-C6-alkyl, or -optionally substituted-Ci-C6-alkyl-(5-6-membered heteroaryl)-alkyl optionally substituted Ci-C6- is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -O-PCOjCR'R1^, amino, (Ci-C4 alkyl)amino -, (Ci-C4 alkyl)(Ci-C^alkyl)-, C1-C4 alkyl, halo(C1-C4 alkyl), halo(Ci-C4 alkoxy)-, C1-C4 alkoxy-, hydroxy-(C2 alkoxy -C4)-, -(C2-C4 alkoxy)-O-P(O)(OH)2, -(C2-C4 alkoxy)-O-P(O)(RIRII)2, and Ci-Cr alkoxy(C1-C4 alkoxy )-; R3 and R5 are each independently -CON(Rd)(Rf), or one of R3 and R5 is -CON(Rd)(Rf), and the other of R3 and R5 is H, COOH or -CO2(Rc); R4 and R6 are each independently selected from H, halogen, halo(Cj-Ce alkyl), halo(Ci-C6 alkoxy)-, hydroxy, -O-P(O)(OH)2, -OΡ(ΟΧ^Π)2, -NH2, -NRcRc, -NRcRd, -CORc, -CO2Rc, -N(Rd)CORc, -N(Rd)SO2Rc, -N(R9)SO2(Ci-C2 alkyl)-N(Rh)(Rf), -N(R9)CO(Ci-C2 alkyl)-N( Rh)(Rf), (Ci-C6 alkyl) optionally substituted, (Ci-C6 alkyl)ox¡- optionally substituted, (Ci-Cejamino-alkyl) optionally substituted, and (Ci-C6 alkyl)(Ci-C4 alkyl)amino - optionally substituted, wherein (CrC6 alkyl) of said (Ci-C6 alkyl) optionally substituted, (CrC6 alkyl)ox¡- optionally substituted, (Ci-Cejamino-alkyl- optionally substituted and (Ci-C6 alkyl)(C1 alkyl) optionally substituted -C4)amino- is optionally substituted with 1-4 substituents each independently selected IF-2019-16742483-APN-ANP#INPI 18 Page 18 of 402 between -OH, -O-P(O)(OH)2, -0-Ρ(0Χ^π)2,-(^ε, -NH2, -NRcRc, -NRcRd, -CO2H, -CO2Rc, - OCORc, -CO2H, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, -NRdSO 2Rc, optionally substituted phenyl, heterocycloalkyl 5-6 membered optionally substituted group and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl, 5-6 membered heterocycloalkyl or 5-6 membered heteroaryl is optionally substituted with 1-4 selected substituents each independently between halogen, hydroxy, O-P(O)(OH)2, -O-PCOXR^'h, amino, (alkyl enjamino-, (alkyl Ci-CjXalkyl Ci-C4)amino-, alkyl Cj-Q, halo(alkyl Cj-Q), hydroxy-(C1-C4 alkyl)-, -(CrC4 alkyl)-O-P(O)(OH)2, -(Ci-C4 alkoxy)-O-P(O)(RiRii)2, halo(alkoxy ¡ C1-C4)-, C1-C4 alkoxy-, hydroxy-(C2-C4 alkoxy)-, -(C2-C|alkoxy)-O-P(O)(OH)2, -(C2-C4 alkoxy)-OPIOOXR 'R11), C1-C4 alkoxy-(alkoxyCrG.)-, -CORd, -CON(Rd)(Rf), and -CO2Rd; R14 is optionally substituted C1-C4 alkyl, wherein said optionally substituted C1-C4 alkyl is optionally substituted with a substituent selected from -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; R16 is H, halogen, or C1-C4 alkyl; R15 and R17 are each independently H, cyclopropyl, or C1-C4 alkyl; Raes H, -Rc, -CORC, -CO2H, -CO2Rc, -SORC, -SO2RC, -CONH2, -CONRcRd, -SO2NH2, or -SO2NRcRd; each Rbes independently C1-C4 alkyl, halo(C1-C4 alkyl), -(Ci-C^-OH alkyl, -(C1-C4 alkyl CrCO-O-PIOXOHh, -(Ci-CQ-O-PIOXR'RHh alkoxy, -(Ci-C4 alkyl)-O-(C1-C4 alkyl), -(Ci-C4 alkyl)-N(Re)(Rf), -(Ci alkyl -C4)-O-CO(C1-C4 alkyl), or -(Ci-Q-CO-OXC1-C4 alkyl); each Rces independently C1-C4 alkyl, halo(Cj-C4 alkyl), -(Ci-C4 alkyl)-OH, -(Cj^-O-PÍOjíOH alkyl),, -(Ci-C4 alkyl)-O-P(O)(R1Rii)2, -(Ci-C4 alkyl)-O-(CrCl alkyl,), -(Ci-C4 alkyl)-N(Re)(Rf), - (Ci-C4 alkyl)-O-CO(C1-C4 alkyl), -(Ci-C4 alkyl)-CO-O-(C1-C4 alkyl), optionally substituted C3-C6 cycloalkyl, optionally substituted phenyl, 4-heterocycloalkyl -6-membered optionally substituted, 5-6-membered heteroaryl optionally substituted, 9-10-membered heteroaryl optionally substituted, -alkylCy-Crdcloalkyl C3-C6optionally substituted, -alkylCrCpphenyl optionally substituted, -alkylCj^-heterocycloalkyl 4-6 optionally substituted 5-6 membered alkyl Ci-Crheteroaryl, or -optionally substituted 9-10 membered alkyl Ci-Crheteroaryl, wherein the moiety C3-C6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, 5-6 membered or 9-10 membered heteroaryl of said cycloalkyl IF-2019-16742483-APN-ANP#INPI19 Page 19 of 402 C3-C6 optionally substituted, phenyl optionally substituted, 4-6 membered heterocycloalkyl optionally substituted, 5-6 membered heteroaryl optionally substituted, 9-10 membered heteroaryl optionally substituted, -CrC4 alkyl-C3-C6 cycloalkyl optionally substituted, -Cj alkyl- Crphenyl optionally substituted, -optionally substituted 4-6 membered alkylCrCrheterocycloalkyl, -optionally substituted 5-6 membered alkylCrCrheteroaryl, or -optionally substituted 9-10 membered alkylCrheteroaryl is optionally substituted with 1-4 selected substituents each independently among halogen, hydroxy, -O-P(O)(OH)2, -O-P(O)(RiRii)2, amino, -(Ci-C4alkyl)NH2, (alkyl CrC^amino-, (alkyl CrQXalkyl CpGOamino -, C1-C4 alkyl, halo(Ci-C4 alkyl), halo(C1-C4 alkoxy)-, CpCr alkoxy, hydroxy-(CrCj alkoxy)-, -(C2-C4 alkoxy)-O-P(O)(OH )2, -(C2-C4 alkoxy)-O-P(O)(RIRn)2, Ci-Cryalkoxy Ci-CQ- alkoxy, -CORd, -CON(Rd)(Rf), and -CO2Rd; each Rdes independently H or CpC^ alkyl; each Rees independently H, (Ci-C» alkyl), -CO(Ci-CO alkyl, -OCO(Ci-CO alkyl C1-C1), -CO2(Ci-C alkyl), -(Ci-C4 alkyl)NH2, -(Ci-Cj alkyl) CrC4 alkoxy, -CO-(optionally substituted 5-6-membered heterocycloalkyl), -CO(optionally substituted 5-6-membered heterocycloalkyl CrQX), -CO( optionally substituted 5-6-membered heteroaryl), -CO(optionally substituted 5-6-membered alkyl-COXheteroaryl), wherein the optionally substituted 5-6-membered heterocycloalkyl or the optionally substituted 5-6-membered heteroaryl is optionally substituted with 1-4 substituents independently selected from halogen, hydroxy, -OP(O)(OH)2, -Ο-Ρ(Ο)^^π)2, amino, (Ci-C4 alkyl)amino-, (Ci-alkyl) C^Xalkyl CrCOamino-, Ci-Q alkyl, halo(Ci-C alkyl), halo(Ci-C^ alkoxy)-, CpCr alkoxy, hydroxy-(C2-C4 alkoxy)-, -(C2 alkoxy- Ci) O-P(O)(OH)2, -(alkoxy Cz-CO-O-PCOXR'R11);,, alkoxy Ci-C4-(alkoxy¡ CpC,)-, -CORd, -CON(Rd)(Rf ), and -CO2Rd; each Rfes independently H or (Ci-Cj alkyl); R9 and Rh are each independently H or (CrQ alkyl) or R9 and Rh, taken together with the atom or atoms through which they are connected, form a 5-6 membered ring; and each occurrence of R1 and Rnes independently (alkyl Ci-Cgjoxi-; or a tautomer thereof; or a salt, in particular a pharmaceutically acceptable salt thereof. IF-2019-16742483-APN-ANP#INPI20 Page 20 of 402 The invention relates to a compound according to the formula (I-P): R4 r16 where: q is 0 or 1; r is 0 or 1; s is 0 or 1; where q + r + s = 1 or 2; when q is 0, RA1 and RA2 are each independently H, halogen, hydroxy, -0P(O)(OH)2, -Ο-Ρ(Ο)(^Π)2, -N(Re)(Rf), -CO2Rf, -N(Rf)CORb, -N(R9)SO2(Ci-C4 alkyl)-N(Re)( Rf), -N(Rs)CO(Ci-C4 alkyl)-N(Rb)(Rf), (Ci-C6 alkyl) optionally substituted, (CrCeJoxy alkyl- optionally substituted, (Ci-Ce alkyl)amino- optionally substituted , and (Ci-C6 alkyl)(optionally substituted Ci-COamino-alkyl, wherein the (Ci-C6 alkyl) of said optionally substituted (Ci-C6 alkyl), (CrCe alkyl)ox¡- optionally substituted, (CrCe alkyl )optionally substituted amino- and (CrC6 alkyl)(optionally substituted Ci-COamino alkyl- is optionally substituted with 1-4 substituents each independently selected from hydroxy, -O-P(O)(OH)2, -Ο-Ρ(Ο)(^Π)2, alkoxy CrCr, -N(Re)(Rf), -CO2(Rf), -CON(Re)(Rf), optionally substituted phenyl, 5-6 membered heterocycloalkyl optionally substituted and an optionally substituted 5-6 membered heteroaryl group, wherein said phenyl IF-2019-16742483-APN-ANP#INPI21 Page 21 of 402 optionally substituted, 5-6 membered heterocycloalkyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -Ο-Ρ(Ο)(^ΚΠ)2, amino, (Ci-QOamino alkyl-, (Ci-C6 alkyl)(Ci-C6 alkyl)amino-, -(Ci-C6 alkyl)-NH2, halo(alkyl Ci-C6), hydroxy-(Ci-Q alkyl)-, -(Ci-C4 alkyl)-O-P(O)(OH)2, -(C1-C4 alkyl)-O-P(O)(RiRii)2, halo (alkoxy CpC,)-, alkoxy CpCr, hydroxy-(alkoxy¡ Cz-C,)-, -(alkoxy CrCO-O-PIOXOHh, -(alkoxy ε2-Ο0-Ο-Ρ(Ο)(^π)2, or alkoxy Ci-CHalkoxy Ci-G,)-; when r is 0, RB1 and RB2 are each independently optionally substituted member, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-10 membered heteroaryl, wherein said optionally substituted Ci-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, C3 cycloalkyl -Cg optionally substituted, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-10 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen , nitro, -Rc, -OH, -O-P(O)(OH)2, -Ο-Ρ(Ο)(^Π)2, -ORC, -NH2, -NRCRC, -NRcRd, -OCORC, -CO2H, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc; when s is 0, RC1 is H, halogen, or CpC alkyl, and RC2 is optionally substituted CpCj alkyl, wherein said optionally substituted CrQ alkyl group is optionally substituted with a substituent selected from -ORC, -NRcRd, -CO2Rc, -CONRcRd, - SO2NRcRd, and -OCONRcRd; when q is 1, RA1 and RA2 are each independently -CH2-, -NRe-, or -O-, and A, taken together with RA1 and RA2, forms a linking group, where A is -halo(Ci-Ci2 alkyl)- , -Ci-Ci2-alkyl- optionally substituted, C2-Ci2-alkenyl optionally substituted, C2-Ci2-alkynyl- optionally substituted, -CrCg-O-alkyl CrC6- optionally substituted, -CrC6-NRa alkyl-Ci-Cg alkyl- optionally substituted, -Ci-C6 alkyl-(C3-C6 cycloalkyl)-Cj-Cg alkyl- optionally substituted, -Ci-C6 alkyl-phenyl- optionally substituted Ci-Cg alkyl, -Ci-C6-alkyl-(4-6-membered heterocycloalkyl)-CrC6-alkyl- optionally substituted, or -CrCg-alkyl-5-6-membered heteroaryl)-Ci-Cg-alkyl- optionally substituted, IF-2019-16742483-APN-ANP#INPI22 Page 22 of 402 wherein the alkyl moiety of said -C1-C12-alkyl- optionally substituted, C2-C12-alkenyl- optionally substituted, C2-Ci2-alkynyl- optionally substituted, -Ci-Ce-O-alkyl-CrC6-alkyl- optionally substituted, -Ci-C6-alkyl-NRa-Ci-C6-alkyl- optionally substituted, -Ci-C6-alkyl-(C3-C6 cycloalkyl)-CrC6-alkyl- optionally substituted, -CrC6-alkyl-phenyI-CrC6-alkyl- optionally substituted, -CrC6-alkyl -(4-6 membered heterocycloalkyl)-CrC6-alkyl- optionally substituted, or -5-6 membered alkylCi-Cg-pheteroaryl)-optionally substituted Cj-Cg-alkyl is optionally substituted by 1-4 substituents each independently selected among halogen, halo(CrC4 alkyl), -OH, -O-P(O)(OH)2, -O-P(O)(R'Rn)2, -ORC, -NH2, -NRcRd, -OCORc, -CO2H, - CO2Rc, -SORC, -SO2RC, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc, and the C3-C6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said -Ci-C6 alkyl-(C3-Ce cycloalkyl)-optionally substituted ΟρΟθ-alkyl, -Ci-C6 alkyl- optionally substituted phenyl-Ci-C6-alkyl, -optionally substituted -Ci-C6-alkyl-(4-6-membered heterocycloalkyl)-optionally substituted-Ci-C6-alkyl, or -optionally substituted-Ci-C6-alkyl-(5-6-membered heteroaryl)-alkyl optionally substituted Ci-C6- is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -O-PIOXR'R11)^ amino, (Ci-C4 alkyl)amino -, (Q-qXalkylCi-C4alkyl)amino-, Ci-C4alkyl, halo(Ci-C»alkyl), halo(Ci-CQ-alkoxy, CpCr-alkoxy, hydroxy-(C1-C4alkoxy)-, -(Ci-C4 alkoxy)-O-P(O)(OH)2, (Ci-C^-O-PfOXR'R11 alkoxy) and CpCHalkoxy Ci-C,)-; when r is 1, RB1 and RB2 are each independently -CH2-, and B, taken together with Rb1 and RB2, forms a linking group, where B is a bond or B is -halo(C1-C10 alkyl)-, -C1 alkyl -C10- optionally substituted, C2-Ci0-alkenyl- optionally substituted, C2-Ci0-alkynyl- optionally substituted, -Ci-C6-alkyl-O-Cj-Ce-alkyl- optionally substituted, -CrC6-NRa-alkyl-Ci-C6-alkyl- optionally substituted, optionally substituted C3-C6cycloalkyl, optionally substituted phenyl, optionally substituted 4-6-membered heterocycloalkyl, optionally substituted 5-6-membered heteroaryl, -Cy-CalkylC3-Cecycloalkyl)-optionally substituted Ci-C4-alkyl, -alkyl Optionally substituted Ci-Q-phenyl-Ci-Cr alkyl, -optionally substituted -Ci-C4-alkyl-(4-6-membered heterocycloalkyl)-C1-C4-alkyl, or -5-6-membered-Cy-Cryheteroaryl-alkyl)-alkyl Ci-C,- optionally substituted, wherein the alkyl moiety of said -C1-C10 alkyl- optionally substituted, alkenyl IF-2019-16742483-APN-ANP#INPI23 Page 23 of 402 C2-Cio- optionally substituted, C2-Cio-alkynyl optionally substituted, -CrC6-O-alkylCrC6-alkyl- optionally substituted, -Ci-C6-NRa-alkyl-CrC6-alkyl- optionally substituted, -CrCXalkyl(C3-C6cycloalkyl)-alkyl CrC4- optionally substituted, -alkyl CrQ-phenyl-C1-C4 alkyl- optionally substituted, -Ci-C alkyl^4-6 membered heterocycloalkyl)-alkyl C1-C4- optionally substituted, or -Ci-alkyl-5-6-membered Cryheteroaryl-C1-C4 alkyl)- optionally substituted is optionally substituted with 1 or 2 substituents each independently selected from halogen, halo(Cj-Ci alkyl), -OH, -O-P(O)(OH)2, -O-P(O)(RiRn)2, -ORC, -NH2, -NRcRd, -OCORC, -CO2H, -CO2Rc, -SORC, -SO2RC, -CONH2, -CONRcRd, -SO2N H2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, - NRdCO2Rc, and -NRdSO2Rc, and the C3-C6 cycloalkyl moiety, phenyl, 4-6 membered heterocycloalkyl or 5-6 membered heteroaryl of said optionally substituted C3-Cg cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl optionally substituted, -CrCrycycloalkylC3-C6alkyl)-C1-C4alkyl- optionally substituted, -CfC^alkylphenyl-C1-C4alkyl- optionally substituted, -Ci-Cralkyl(4-6 membered heterocycloalkyl)-alkyl C1-C4- optionally substituted, or -CrCr(5-6 membered heteroaryl)alkyl-optionally substituted C1-C4-alkyl is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)( OH)2, Ο-Ρ(Ο)(^Π)2, amino, (Ci-C4 alkyl)amino-, (Ci-C4 alkyl)(Ci-Qamino-alkyl, Ci-C4 alkyl, halo(Cj-alkyl C4), halo(Ci-C» alkoxy)-, CpCr alkoxy, hydroxy-(C2-C0 alkoxy-, (C2-C0 alkoxy O-P(O)(OH)2, -((Ζ2-Ο) alkoxy)-0- Ρ(0)(^π)2, and alkoxy Cj-CHalkoxy C1-C0-; when s is 1, RC1 and Rc2 are each independently -CH2-, and O taken together with RC1 and RC2, forms a linking group, where C is -halo(Ο-Ο2 alkyl)-, -optionally substituted Ci-Ci2 alkyl, C2-Cj2- alkenyl optionally substituted, C2-Ci2-alkynyl optionally substituted, -Ci-Ce-O alkyl-optionally substituted 0-0' alkyl, -Ci-C6-alkyl-NRa-Ci-C6 alkyl- optionally substituted, -alkyl Ci-C6-(C3-C6 cycloalkyl)-CpCe-alkyl- optionally substituted, -Ci-C6-alkyl-phenyl-alkyl Ci-C6- optionally substituted, -Cj-Cg-alkyl-4-6-membered heterocycloalkyl)-CrCe-alkyl- optionally substituted, or -Ci-C6-alkyl-(5-6-membered heteroaryl)-Ci-Ce-alkyl- optionally substituted , wherein the alkyl moiety of said -optionally substituted CrCi2-alkyl, optionally substituted C2-Ci2-alkenyl, optionally substituted C2-Ci2-alkynyl, -alkyl IF-2019-16742483-APN-ANP#INPI 24 Page 24 of 402 CrC6-O-Ci-C6-alkyl- optionally substituted, -Ci-C6-alkyl-NRa-CrC6-alkyl- optionally substituted, -CrC6-alkyl-(C3-C6 cycloalkyl)-CrCg-alkyl- optionally substituted, -Ci-C6-alkyl-phenyl -Ci-C6-alkyl- optionally substituted, -CrC6-alkyl-(4-6-membered heterodcloalkyl)-alkyl CrC6- optionally substituted, or -Ci-C6-alkyl-(5-6 membered heteroaryl)-optionally substituted CrC6-alkyl is optionally substituted with 1 or 2 substituents each independently selected from halogen, halo(Ci-C4 alkyl), - OH, -O-P(O)(OH)2, -Ο-Ρ(Ο)(^π)2, -ORc, -NH2, -NRcRd, -OCORc, -CO2H, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and - NRdSO2Rc, and the C3-C6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said optionally substituted -Ci-C6 alkyl-(C3-C6 cycloalkyl)-Cj-Ce-alkyl, -Ci-alkyl C6-phenyl-Ci-C6-alkyl- optionally substituted, -CrC6-alkyl-(4-6-membered heterocycloalkyl)-optionally substituted CrCe-alkyl, or -Ci-C6-alkyl-(5-6-membered heteroaryl)-Ci-alkyl- C6- optionally substituted is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -Ο-Ρ(Ο)^^Π)2, amino, (alkyl Ci- C^amino-, (Ci-C4 alkyl)(Ci-C^amino-alkyl, Ci-C^ alkyl, halo(Ci-C4 alkyl), halo(Ci-C4 alkoxy)-, Ci-Q alkoxy-, hydroxy-(C2-C4 alkoxy)-, -(CrCO-OP(O)(OH)2 alkoxy, -(σ2-α0-Ο-Ρ(Ο)(^π)2 alkoxy, and Ci-Cryalkoxy Ci alkoxy -C,)-; R3 and R5 are each independently -CON(Rd)(Rf), or one of R3 and R5 is -CON(Rd)(Rf), and the other of R3 and R5 is H, COOH or -CO2(RC); R4 and R6 are each independently selected from H, halogen, halo(Ci-C6 alkyl), halo(CrC6 alkoxy)-, hydroxy, -O-P(O)(OH)2, -OΡ(Ο)(^Π)2, - NH2, -NRcRc, -NRcRd, -CORc, -CO2Rc, -N(Rd)CORc, -N(Rd)SO2Rc, -N(R9)SO2(Ci-C2 alkyl)-N(Rh)(Rf), - N(R9)CO(Cj-C2 alkyl)-N(Rh)(Rf), (CpCe alkyl) optionally substituted, (Ci-C6 alkyl)ox¡- optionally substituted, (Ci-C6 alkyl)amino- optionally substituted, and (Ci-C6 alkyl)(optionally substituted Ci-C^amino-alkyl, wherein the (CrC6 alkyl) of said optionally substituted (Ci-C6 alkyl), (Ci-C6 alkyl)ox¡- optionally substituted, (Ci-C6 alkyl) Ci-Cejamino- optionally substituted and (alkyl Ci-CeXalkyl CrC4)amino- optionally substituted is optionally substituted with 1-4 substituents each independently selected from -OH, -O-P(O)(OH)2, -O-P(O)( RIRn)2,-ORc, -NH2, -NRCRC, IF-2019-16742483-APN-ANP#INPI25 Page 25 of 402 -NRcRd, -CO2H, -CO2Rc, -OCORc, -CO2H, -CO2Rc, -SORc, -SO2Rc, -CONH2z -CONRcRd, -S O2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc , -NRdSO2Rc, optionally substituted phenyl, optionally substituted 5-6-membered heterocycloalkyl and an optionally substituted 5-6-membered heteroaryl group, wherein said optionally substituted phenyl, 5-6-membered heterocycloalkyl or 5-6-membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -Ο-Ρ(Ο)(Ρ^Π)2, amino, (alkyl Ci-COamino-, (alkyl CpCjXalkyl Ci-Qamino-, C1-C4 alkyl, halo(C1-C4 alkyl), hydroxy-(C1-C4 alkyl)-, -(Ci-C4 alkyl)-O-P(OXOH)2, -(Ci-Cjj-O-PIOjíR’R1^ alkoxy, halo(C1-C4 alkoxy)-, alkoxy C1-C4-, hydroxy-(C2-C4 alkoxy)-, -(C2-C4 alkoxy)-O-P(O)(OH)2, -(alkoxy ^-0,)-0Ρ(ΟΧ^Π)2, alkoxy Ci-C4-(alkoxy¡ Cj-Q)-, -CORd, -CON(Rd)(Rf), and -CO2Rd; R14 is optionally substituted C1-C4 alkyl, wherein said optionally substituted C1-C4 alkyl is optionally substituted with a substituent selected from -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; R16is H, halogen, or CrQ alkyl; R15 and R17 are each independently H, cyclopropyl, or C1-C4 alkyl; Raes H, -Rc, -CORc, -CO2H, -CO2Rc, -SORC, -SO2RC, -CONH2, -CONRcRd, -SO2NH2, or -SO2NRcRd; each Rbes independently C1-C4 alkyl, halo(C1-C4 alkyl), -(Ci-C^-OH alkyl, -(Ci-C4 alkyl)-O-P(O)(OH)2, -(Ci-C4 alkoxy)-O-P(O)(R!Rn)2, -(Cj-QO-OXalkyl Q-Q), or -( alkyl Ci-GO-NÍR'Xtf), -(alkyl Ci-CQ-O-CCXalkyl CpG,), or -(alkyl CrQ-CO-OXalkyl C!-C4); each Rces independently Ci-C4 alkyl, halo(CpCt alkyl), -(Ci-CO-OH alkyl, -(Ci-Q-O-PÍOXOHh alkyl, -(alkyl Cr^-O-PfOJfR'R11)^ -(alkyl CrQ-O-alkyl Cj-C,), -(alkyl ¢^-0,)-14^(^), -(alkyl Ci-C4) -O-CO(Ci-Q alkyl), -(Ci-qj alkyl-CO-O-Cj-C alkyl), optionally substituted C3-C6 cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, 5-6 membered optionally substituted, 9-10 membered heteroaryl optionally substituted, -Ci-C alkyl, -C3-C6 cycloalkyl optionally substituted, -CpCt alkyl-phenyl optionally substituted, -Ci-C4 alkyl-heterocycloalkyl optionally substituted substituted, -optionally substituted -Ci-C^alkyl-5-6 membered heteroaryl, or -optionally substituted -Ci-C4alkylheteroaryl, wherein the moiety C3-Ce cycloalkyl, phenyl, 4-6 membered heterocycloalkyl , 35 5-6 membered heteroaryl or 9-10 membered heteroaryl of said cycloalkyl C3-Cg optionally substituted, phenyl optionally substituted, heterocycloalkyl of IF-2019-16742483-APN-ANP#INPI26 Page 26 of 402 4-6 membered optionally substituted, 5-6 membered optionally substituted heteroaryl, 9-10 membered heteroaryl optionally substituted, -Ci-C4 alkyl-C3-C6 cycloalkyl optionally substituted, -Ci-Crphenyl alkyl optionally substituted, -Ci-Crheterocycloalkyl alkyl 4-6 membered optionally substituted, -optionally substituted 5-6 membered -alkyl Ci-Crheteroaryl, or -optionally substituted 9-10 membered -alkyl Ci-Crheteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxy , -O-P(O)(OH)2, -Ο-Ρ(θ)(ΐνρπ)2, amino, -(Ci-C4 alkyl)NH2, (Ci-C^alkyl)amino-, (Cr^yalkyl Ci-C4)amino-, CrCá alkyl, halo(alkyl C1-C4), halo(C1-C4 alkoxy)-, CrCr alkoxy, hydroxy-(C2-C4 alkoxy)-, -(C2-C4 alkoxy)-O-P(O)(OH)2, -(alkoxy CrGO-O-PIOXR’R11)^ alkoxy CrC4-(alkoxy C1-C4)-, -CORd, -CON(Rd)(Rf), and -CO2Rd; each Rdes independently H or CrCj alkyl; each Rees independently H, (CrC alkyl}), -CO(CpCO alkyl, -OCO(CpCO alkyl CrCt), -CO2(Cj-C alkyl»), -(Ci-C4 alkyl)NH2, -(CrC4 alkyl) C1-C4 alkoxy, -CO-(optionally substituted 5-6 membered heterocycloalkyl), -CO(optionally substituted 5-6 membered heterocycloalkyl), - CO(optionally substituted 5-6-membered heteroaryl), -CO(optionally substituted 5-6-membered heteroaryl), -CO(optionally substituted 5-6-membered heteroaryl), wherein the optionally substituted 5-6-membered heterocycloalkyl or the 5-6-membered heteroaryl optionally substituted members are optionally substituted with 1-4 substituents independently selected from halogen, hydroxy, -OP(O)(OH)2, -O-PIOXR'R11);,, amino, (alkyl Ci-CQamino-, (alkyl Ci -CtXalkyl Ci-C^amino-, C4-C4 alkyl, halo(C1-C4 alkyl), halo(alkoxy¡ Ci-C^-, alkoxy Ci-C»-, hydroxy-(alkoxy¡ C2-C4)-, -(C2-C4 alkoxy) O-P(O)(OH)2, -(C2-C4 alkoxy)-O-P(O)(RIRn)2, Ci-C4 alkoxy-(CpCi alkoxy)-, -CORd, -CON(Rd)(Rf), and -CO2Rd; each Rfes independently H or (C1-C4 alkyl); R9 and Rh are each independently H or (Ci-C alkyl) or R9 and Rh, taken together with the atom or atoms through which they are connected, form a 5-6 membered ring; and each occurrence of R1 and Rnes independently (Ci-Cg alkyl)oxy-; or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. IF-2019-16742483-APN-ANP#INPI27 Page 27 of 402 Another aspect of the present invention relates to compounds of formula (I) R4 R16 R17(I) where: q is 0 or 1; r is 0 or 1; s is 0 or 1; where q + r + s = 1 or 2; when q is 0, RA1 and RA2 are each independently H, halogen, hydroxy, -N(Re)(Rf), -CO2Rf, -N(Rf)CORb, -N(R9)SO2(Ci-C4 alkyl)-N( Re)(Rf), -N(R9)CO(Ci-C4 alkyl)-N(Rb)(Rf), (Ci-C6 alkyl) optionally substituted, (Ci-Cgjoxy-alkyl) optionally substituted, (alkyl Ci-C6)amino- optionally substituted, and (Ci-C6 alkyl)(optionally substituted Ci-C^alkyl), wherein the (Ci-C6 alkyl) of said (Ci-C6 alkyl) optionally substituted, (Ci alkyl -C6)ox¡- optionally substituted, (optionally substituted Ci-Cgjamino alkyl- and (optionally substituted Ci-C6 alkyl)(optionally substituted Ci-COamino alkyl-) is optionally substituted with 1-4 substituents each independently selected from hydroxy, Cj alkoxy- C,-, -N(Re)(Rf), -CO2(Rf), -CON(Re)(Rf), optionally substituted phenyl, optionally substituted 5-6-membered heterocycloalkyl and an optionally 5-6-membered heteroaryl group substituted, wherein said optionally substituted phenyl, 5-6 membered heterocycloalkyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents selected each IF-2019-16742483-APN-ANP#INPI 28 Page 28 of 402 one independently of halogen, hydroxy, amino, (CrC6 alkyl)amino-, (CrC6 alkyl)(Ci-C6 alkyl)amino-, halo(Ci-C6 alkyl), hydroxy-(C1-C4 alkyl)- , halo(C1-C4 alkoxy)-, C1-C4 alkoxy-, hydroxy-(C2-C4 alkoxy)-, and Ci-C4 alkoxy-(C1-C4 alkoxy)-; when r is 0, RB1 and RB2 are each independently optionally substituted, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-10 membered heteroaryl, wherein said optionally substituted Ci-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C3-C6 cycloalkyl, heterocycloalkyl optionally substituted 4-6 membered, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-10 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, nitro, -Rc, -OH, -ORC, -NH2, -NRCRC, -NRcRd, -OCORc, -CO2H, -CO2Rc, -SORC, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc , -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc; when s is 0, RC1 is H, halogen, or C1-C4 alkyl and RC2 is optionally substituted C1-C4 alkyl, wherein said optionally substituted C1-C4 alkyl group is optionally substituted with a substituent selected from -ORC, -NRcRd, -CO2Rc , -CONRcRd, -SO2NRcRd, and -OCONRcRd; when q is 1, RA1 and RA2 are each independently -CH2-, -NRe-, or -O-, and A, taken together with RA1 and RA2, forms a linking group, where A is -halo(CrCi2 alkyl)-, - CrCi2- alkyl optionally substituted, C2-Ci2- alkenyl optionally substituted, C2-Ci2- alkynyl optionally substituted, -Cj-Cg-O-alkyl Ci-C6- optionally substituted, -Cj-C6-alkyl-NRa-Ci-C6-alkyl- optionally substituted, -Ci-C6-alkyl-(C3-C6 cycloalkyl)-Ci-C6-alkyl- optionally substituted, -Ci-C6-alkyl- optionally substituted phenyl-Ci-Qr alkyl, -optionally substituted -Ci-C6-alkyl-(4-6-membered heterocycloalkylj-optionally substituted Ci-C6-alkyl, or -Ci-C6-alkyl-(5-6-membered heteroarylj-Ci-C6-alkyl - optionally substituted, wherein the alkyl moiety of said -CrCi2-alkyl- optionally substituted, C2-Ci2-alkenyl optionally substituted, C2-Ci2-alkynyl- optionally substituted, -Cj-Cg-O-alkylCrC6-alkyl- optionally substituted, -alkyl CrC6-NRa-CrC6-alkyl- optionally substituted, -CrC6-alkyl-(C3-C6 cycloalkyl)-CrC6-alkyl- optionally substituted, -CrC6-alkyl-phenyl-Ci-C6-alkyl- optionally IF-2019-16742483-APN-ANP#INPI 29 Page 29 of 402 substituted, -CrCg-alkyl-(4-6-membered heterocycloalkyl)-CrCg-alkyl- optionally substituted, or -optionally substituted-Ci-Cg-alkyl-(5-6-membered heteroaryl)-Ci-Cg-alkyl- is substituted optionally by 1-4 substituents each independently selected from halogen, halo(C1-C4 alkyl), -OH, -ORC, -NH2, -NRcRd, -OCORc, -CO2H, -CO2Rc, -SORC, -SO2RC, -CONH2 , -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc, and the C3-C6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said optionally substituted -CrCg alkyl-(C3-Cg cycloalkyl)-Ci-Cg alkyl-, -Ci-Cg alkyl- phenyl-alkylCrCg- optionally substituted, -alkylCrCg-(5-6-membered heteroaryl)-alkylCrCg- optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, amino, (CrC4alkyl)amino-, (CrQXalkylCrC^amino-, C1-C4alkyl, halo(CrQalkyl), halo(C1-C4alkoxy) -, C1-C4 alkoxy-, hydroxy-(Ο,-C, alkoxy)-, and CrC4 alkoxy-(CrQ alkoxy)-; when r is 1, RB1 and RB2 are each independently -CH2-, and B, taken together with RB1 and Rb2, forms a linking group, where B is a bond or B is -halo(C1-C10 alkyl)-, -CrCi0 alkyl - optionally substituted, optionally substituted C2-Ci0-alkenyl, optionally substituted C2-Ci0-alkynyl, -CrCg-O-alkyl CrCg- optionally substituted, -alkyl CrCg-NRa-alkyl CrCg- optionally substituted, C3-C6 cycloalkyl optionally substituted, phenyl optionally substituted, 4-6-membered heterocycloalkyl optionally substituted, 5-6-membered heteroaryl optionally substituted, -alkylCrC4- (C3-Cg cycloalkyl)-C1-C4-alkyl-optionally substituted, -CrCrphenyl-alkyl-optionally substituted CrCr-alkyl, -4-6-membered CrCryheterocycloalkyl)-optionally substituted Cj-Gr-alkyl, or -CrC4-alkyl-(5-membered heteroaryl) -6 membered)-optionally substituted CrCr alkyl, wherein the alkyl moiety of said -CrCio alkyl- optionally substituted, C2-Cjo- alkenyl optionally substituted, C2-Cio alkynyl- optionally substituted, -CrCg-alkyl-O-CrCg alkyl- optionally substituted, -alkyl CrCg-NRa-alkyl CrCg- optionally substituted, -alkyl Ci-CLj-ícycloalkyl C3-C6)-alkyl CrCr optionally substituted, -alkyl CrCrphenyl-alkyl CrC4- optionally substituted, -alkyl CrCr(4-6 heterocycloalkyl members)-alkyl CrCr optionally substituted, or -alkyl CrCr(5-6 membered heteroaryl-alkyl CrCj)- optionally substituted is optionally substituted with 1 or 2 IF-2019-16742483-APN-ANP#INPI30 Page 30 of 402 substituents each independently selected from halogen, halo(CrC4 alkyl), -OH, -ORC, -NH2, -NRcRd, -OCORc, -CO2H, -CO2Rc, -SORC, -SO2RC, -CONH2, -CONRcRd , -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc, and the C3-C6 cycloalkyl moiety, phenyl, 4-6 membered heterocycloalkyl or 5-6 membered heteroaryl of said optionally substituted C3-C6 cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl substituted, -Ci-Oj-C3-C6 alkyl-Ccycloalkyl)-Ci-C4 alkyl- optionally substituted, -CrQ alkyl-phenyl-CrQ alkyl- optionally substituted, -4-6 membered alkylCrCXheterocycloalkyl)-CrC4 alkyl- optionally substituted, or -optionally substituted -alkylCy-CXheteroaryl)-alkylCrQ- is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, amino, (alkylCi-C^amino-, (alkylCrQXalkylCi -C^amino-, CrCi alkyl, halo(Cj-Q alkyl), halo(Ci-Gj alkoxy)-, Ci-C» alkoxy-, hydroxy-(C2-C4 alkoxy)-, and Ci-C4 alkoxy- (Ci-Ci alkoxy)-; I when s is 1, RC1 and RC2 are each independently -CH2-, and C, taken together with RC1 and RC2, forms a linking group, where C is -halo(CrCi2 alkyl)-, - optionally substituted Ci-Ci2-alkyl, optionally substituted C2-Ci2-alkenyl, optionally substituted C2-Ci2-alkynyl, -Ci-C6-alkyl-O-optionally substituted Ci-C6-alkyl, -Ci-C6-alkyl-NRa-Ci-C6-alkyl - optionally substituted, -Ci-C6 alkyl-(C3-Ce cycloalkyl)-Ci-Ce alkyl- optionally substituted, -Ci-Ce alkyl-phenyl-alkyl CrCe- optionally substituted, -Ci-C6 alkyl-(4-6 membered heterocycloalkyl)-Ci-C6 alkyl- optionally substituted, or -Ci-C6 alkyl-(5-6 membered heteroarylj-CpCe alkyl- optionally substituted, in wherein the alkyl moiety of said -Cj-Ci2-alkyl- optionally substituted, C2-Ci2-alkenyl optionally substituted, C2-Ci2-alkynyl- optionally substituted, -Ci-C6-alkyl-O-CrCe-alkyl- optionally substituted, -CrC6-NRa alkyl -Ci-C6 alkyl- optionally substituted, -Ci-CeX alkyl(C3-C6 cycloalkyl)-Ci-C6 alkyl- optionally substituted, -Ci-C6 alkyl-phenyl-CrCe alkyl- optionally substituted, -Ci-C6 alkyl-(heterocycloalkyl) 4-6 members)-alkyl CrC6- optionally substituted, or -alkyl CrCeX5-6 membered heteroaryl)-optionally substituted Ci-C6-alkyl is optionally substituted with 1 or 2 substituents each independently selected from halogen, halo(Ci-C4 alkyl), -OH, - ORC, -NH2, -NRcRd, -OCORc, -CO2H, IF-2019-16742483-APN-ANP#INPI31 Page 31 of 402 -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRCRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc, and the C3-C6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said -Ci-Cg alkyl-C3-Ce cycloalkyl)-optionally substituted Ci-C6 alkyl, -Cj-Cg alkyl -phenyl-Ci-C6-alkyl- optionally substituted, -Ci-C6-alkyl-(4-6-membered heterocycloalkyl)-optionally substituted Ci-C6-alkyl, ο -Ci-C6-alkyl-(5-6-membered heteroaryl)- optionally substituted Ci-C6-alkyl is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, amino, (CrQjamino-alkyl, (Ci-C4-alkyl)(Ci-CQamino-alkyl, C1-C4-alkyl, halo (C1-C4 alkyl), halo(C1-C4 alkoxy)-, C1-C4 alkoxy-, hydroxy-(CrC alkoxy)-, and CrCHalkoxy Cj-C alkoxy)-; R3 and R are each independently -CON(Rd)(Rf), or one of R3 and R5 is -CON(Rd)(Rf), and the other of R3 and R5 is H or -CO2(Rc); R4 and R6 are each independently selected from H, halogen, halo(alkyl CrC6), halo(alkoxy CrCg)-, hydroxy, -NH2, -NRCRC, -NRcRd, -CORc, -CO2Rc, -N(Rd)CORc, -N (Rd)SO2Rc, -N(R9)SO2(CrC2 alkyl)-N(Rh)(Rf), -N(R9)CO(Ci-C2 alkyl)-N(Rh)(Rf), (CrCe alkyl) optionally substituted, (CrCe alkyl)oxy- optionally substituted, (C!-C6 alkyl)amino- optionally substituted, and (Ci-C6 alkyl)(Ci-C^alkyl amino- optionally substituted, wherein (Ci-C6 alkyl) of said (Ci-Q alkyl) optionally substituted, (Ci-C6 alkyl)ox¡- optionally substituted, (Ci-CeJamino alkyl- optionally substituted and (Ci-C6 alkyl) (optionally substituted Ci-COamino alkyl) is optionally substituted with 1-4 substituents each independently selected from -OH, -ORC, -NH2, -NRCRC, -NRcRd, -CO2H, -CO2Rc, -OCORc, -CO2H, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd , -SO2NH2, -SO2NRcRd, -OC ONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, -NRdSO2Rc, optionally substituted phenyl, optionally substituted 5-6-membered heterocycloalkyl and an optionally substituted 5-6-membered heteroaryl group, wherein said optionally substituted phenyl, 5-6 membered heterocycloalkyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxy, amino, (alkyl Ci-GOamino-, (alkyl Ci- C4)(Ci-C^amino-alkyl, C1-C4 alkyl, halo(Cj-C alkyl), hydroxy-(C1-C4 alkyl)-, halo(C4-C4 alkoxy)-, C1-C4 alkoxy -, hydroxy-(C2-Gi alkoxy)-, Cj-CAalkoxy C1-C4), -CORd, -CON(Rd)(Rf), and -CO2Rd; R14 is optionally substituted C1-C4 alkyl, wherein said C1-C4 alkyl optionally IF-2019-16742483-APN-ANP#INPI32 Page 32 of 402 substituted is optionally substituted with a substituent selected from -ORC, -NRcRd, -CO2Rc, -CONRcRd, -SO2NRcRd, and -OCONRcRd; R16is H, halogen, or CrC alkyl»; R15 and R17 are each independently H, cyclopropyl, or C»-C4 alkyl; Raes H, -Rc, -CORc, -CO2H, -CO2Rc, -SORC, -SO2RC, -CONH2, -CONRcRd, -SO2NH2, or -SO2NRcRd; each Rbes independently C1-C4 alkyl, halo(CrC»alkyl), -(CrC»alkyl)-0H, -(CrC4alkyl)-O-(CrC»alkyl), -(CrC»alkyl)-N(Re)( Rf), -(CrC»alkyl)-O-CO(CrC4alkyl), or -(CrC»alkyl)-CC)-O-(C»-C»alkyl); each Rces independently alkyl CrC», halo(alkyl CrC»), -(alkyl CrC»)-OH, -(alkyl C!-C4)-O-(alkyl CrC»), -(alkyl CrC»)-N(Re )(Rf), -(CrC alkyl)-O-CO(CpC alkyl), -(Ci-C4 alkyl)-CO-O-(CrQ alkyl), optionally substituted C3-Cg cycloalkyl, optionally substituted phenyl, heterocycloalkyl optionally substituted 4-6-membered heteroaryl, optionally substituted 5-6-membered heteroaryl, optionally substituted 9-10-membered heteroaryl, -optionally substituted CrC4alkyl-C3-Cgcycloalkyl, -optionally substituted CrCyalkylphenyl, -CrC»alkyl- optionally substituted 4-6 membered heterocycloalkyl, -optionally substituted -CrC»alkyl-5-6 membered heteroaryl, or -optionally substituted -Cy-C4 alkyl-heteroaryl, wherein the moiety C3-C6 cycloalkyl, phenyl, heterocycloalkyl 4-6 membered heteroaryl, 5-6 membered heteroaryl or 9-10 membered heteroaryl of said C3-C6 substituted cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, 9-10 membered optionally substituted, -Ci-C4alkyl-C3-C6cycloalkyl optionally substituted, -CrC»alkyl-phenyl optionally substituted, -Cy-Crheterocycloalkyl optionally substituted 4-6 membered, -CrCrheteroaryl alkyl optionally substituted 5-6 membered substituted, or -optionally substituted 9-10 membered Ci-C4 alkyl-heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxy, amino, (CrC4 alkyl)amino-, (CrC alkyl) (CrC4alkyl)amino-, CrC4alkyl, halo(CrCalkyl), halo(Ci-C»alkoxy)-, CrC»alkoxy-, hydroxy-(C2-C4alkoxy)-, Ci-Cralkoxy(alkoxy CrC»)-, -CORd, -CON(Rd)(Rf), and -CO2Rd; each Rdes independently H or alkyl CrC»; each Rees independently H, (CrC alkyl»), -CO(CrC» alkyl), -OCO(CrC alkyl CrC»), -CO2(CrC alkyl»), -CO-(optionally substituted 5-6 membered heterocycloalkyl), -CO(optionally substituted CrC alkyl)-(optionally substituted 5-6 membered heterocycloalkyl), -CO(optionally substituted 5-6 membered heteroaryl), -CO(Ci-C4 alkyl)-(5-6 membered heteroaryl IF-2019-16742483-APN-ANP#INPI33 Page 33 of 402 optionally substituted), wherein the optionally substituted 5-6 membered heterocycloalkyl or the optionally substituted 5-6 membered heteroaryl is optionally substituted with 1-4 substituents independently selected from halogen, hydroxy, amino, (CrC4 alkyl) amino-, (Ci-QXalkylCi-C^amino-alkyl, Cj-C4 alkyl, halo(CrQ alkyl), halo(Ci-Gj alkoxy)-, Cj-Q-alkoxy, hydroxy-(CrC alkoxy») -, alkoxy CrCHalkoxy Ci-CO-, -CORd, -CON(Rd)(Rf), and -CO2Rd; each Rfes independently H or (Ci-Ci alkyl); R9 and Rh are each independently H or (Ci-Q alkyl) or R9 and Rh, taken together with the atom or atoms through which they are connected, form a 5-6 membered ring; or a tautomer thereof; or a salt, in particular a pharmaceutically acceptable salt thereof. The alternative definitions for the various groups and substituent groups of formula (I-N), (I) or formula (I-P) provided throughout the specification are intended to particularly describe each species of compound disclosed herein, individually, as well as of one or more species of compounds. The scope of the present invention includes any combination of these group and substituent group definitions. The compounds of the invention are only those that are contemplated as chemically stable, as will be appreciated by those skilled in the art. Those skilled in the art will appreciate that the compounds of the present invention may exist in other tautomeric forms including zwitterionic or isomeric forms. All tautomeric (including zwitterionic forms) and isomeric forms of the formulas and compounds described herein are intended to be encompassed within the scope of the present invention. Those skilled in the art will also appreciate that the compounds of the present invention may exist in tautomeric forms including, but not limited to, formula (A), formula (B) and / or formula (C) or the forms zwitterionics including, but not limited to, formula (D) or formula (E). IF-2019-16742483-APN-ANP#INPI 34 Page 34 of 402 Formula (A) Formula (B) Formula (C) Formula (D) Formula (E) The chemical names provided for the intermediate compounds and / or the compounds of the present invention described herein may refer to any one of the tautomeric representations of said compounds (in some cases, such alternative names are provided in the experimental part). It should be understood that any reference to a named compound (an intermediate compound or a compound of the invention) or a structurally illustrated compound (an intermediate compound or a compound of the present invention) is intended to encompass all tautomeric forms including zwitterionic forms of said compounds and any mixture thereof. As used herein, the term alkyl represents a linear or branched saturated hydrocarbon group having the specified number of carbon atoms. The term CpCT alkyl refers to a linear or branched alkyl moiety containing 1 to 4 carbon atoms. Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, pentyl and hexyl. When a substituent term, such as alkyl, is used in combination with another substituent term, for example, as in hydroxy(Ci-C4 alkyl), the term of the linking substituent (e.g., alkyl) is intended to encompass a bivalent moiety, wherein the point of attachment is through that linker substituent. Examples of hydroxy(CrC alkyl) groups include, but are not limited to, hydroxymethyl, hydroxyethyl, and hydroxyisopropyl. As used herein, the term halo(alkyl) represents a linear or branched saturated hydrocarbon group having the specified number (n) of carbon atoms and one or more (up to 2n+l) halogen atoms. For example, the term halo(C1-C4 alkyl) represents a group having one or more halogen atoms, which may be the same or different, on one or more carbon atoms of an alkyl moiety containing 1 to 4 atoms. carbon. Examples of halo(C1-C4 alkyl) groups include, but are not limited to, -CF3 (trifluoromethyl), -CCI3 (trichloromethyl), 1,1-difluoroethyl, 2,2,2-trifluoroethyl, and hexafluoroisopropyl. Alkenyl refers to a linear or branched hydrocarbon group having the number IF-2019-16742483-APN-ANP#INPI35 Page 35 of 402 specified carbon atoms and at least 1 to 3 carbon-carbon double bonds. Examples include ethenyl and propendend. Alkynyl refers to a linear or branched hydrocarbon group having the specified number of carbon atoms and at least 1 to 3 carbon-carbon triple bonds. Examples include ethinyl and propynyl. Alkoxy- or (alkyl)oxy- refers to an alkyl-oxy- group, containing an alkyl moiety, having the specified number of carbon atoms, linked through an oxygen linker atom. For example, the term Cj-Cr alkoxy represents a linear or branched saturated hydrocarbon moiety having at least 1 and up to 4 carbon atoms linked through an oxygen linker atom. Exemplary CrC4-alkoxy or (Ci-COoxy-alkyl) groups include, but are not limited to, methoxy, ethoxy, / 7-propoxy, isopropoxy, butoxy, s-butoxy, and f-butoxy. As used herein, the term halo(alkoxy) represents a linear or branched saturated hydrocarbon group having the specified number (n) of carbon atoms and one or more (up to 2n+l) halogen atoms, attached through a linker oxygen atom. For example, the term halo(Ci-Q alkoxy)- refers to a halo alkyl-oxy- group, which contains a halo(Cj-Ct alkyl) moiety attached through a linker oxygen atom. Exemplary halo(alkoxy Ci-CO groups include, but are not limited to, -OCHF2(difluoromethoxy), -OCF3(trifluoromethoxy), -OCH2CF3(trifluoroethoxy), and -OCH(CF3)2(hexafluoroisopropoxy). A carbocyclic group or moiety is a cyclic group or moiety in which the ring members are carbon atoms, which may be saturated, partially unsaturated (non-aromatic), or completely unsaturated (aromatic). Cycloalkyl refers to a saturated, non-aromatic hydrocarbon ring group containing the specified number of carbon atoms in the ring. For example, the term C3-C6 cycloalkyl refers to a cyclic group having three to six ring carbon atoms. Exemplary C3-C6 cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. A heterocyclic group or moiety is a cyclic group or moiety that has, as members of the ring, atoms of at least two different elements, said cyclic group or moiety being saturated, partially unsaturated (non-aromatic) or completely unsaturated (aromatic). Heteroatom refers to a nitrogen, sulfur or oxygen atom, for example, a nitrogen atom or an oxygen atom. Heterocycloalkyl refers to a monocyclic or bicyclic non-aromatic group containing 3-10 ring atoms and containing one or more (generally one or two) ring members of heteroatoms independently selected from oxygen, sulfur, and nitrogen. The point of attachment of a heterocycloalkyl group may be through any suitable carbon or nitrogen atom. IF-2019-16742483-APN-ANP#INPI36 Page 36 of 402 Examples of heterocycloalkyl groups include, but are not limited to, aziridinyl, thiyranyl, oxiranyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, 1,3-dioxolanyl, piperidinyl, piperazinyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, 1,3-dioxanyl , 1,4-dioxanyl, 1,3-oxathiolanyl, 1,3-oxatianyl, 1,3-dithianyl, 1,4-oxathiolanyl, 1,4-oxathiolanyl, 1,4-dithianyl, morpholinyl, thiomorpholinyl, and hexahydro-l / / -l,4-diazepine. Examples of 4-membered heterocycloalkyl include oxetanyl, thietanyl and azetidinyl. The term 5-6 membered heterocycloalkyl represents a saturated monocyclic group, containing 5 or 6 ring atoms, including one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen. Illustrative examples of 5-6 membered heterocycloalkyl groups include, but are not limited to, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, piperazinyl, morpholinyl, and thiomorpholinyl. Heteroaryl refers to a monocyclic or bicyclic aromatic group containing 5 to 10 ring atoms, including 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur, where at least a part of the group is aromatic. For example, this term encompasses bicyclic heterocycloalkyl groups containing either a phenyl ring fused to a heterocyclic moiety or a heteroaryl ring moiety fused to a carbocyclic moiety. The point of attachment of a heteroaryl group may be through any suitable carbon or nitrogen atom. The term 5-6 membered heteroaryl represents a monocyclic aromatic group containing 5 or 6 ring atoms, including at least one carbon atom and 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur. Selected 5-membered heteroaryl groups contain one nitrogen, oxygen, or sulfur ring heteroatom, and optionally contain 1, 2, or 3 additional nitrogen ring atoms. Selected 6-membered heteroaryl groups contain 1, 2, or 3 nitrogen ring heteroatoms. Examples of 5-membered heteroaryl groups include furyl (furanyl), thienyl, pyrrolyl, imidazolyl, pyrazolyl, thnazolyl, tetrazolyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, and oxadiazolyl. Selected 6-membered heteroaryl groups include pyridinyl (pyridyl), pyrazinyl, pyrimidinyl, pyridazinyl and triazinyl. The term 9-10 membered heteroaryl refers to a bicyclic aromatic group containing 9 or 10 ring atoms, including 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur. Examples of 9-membered heteroaryl (6,5-fused heteroaryl) groups include benzothienyl, benzofuranyl, indolyl, indolinyl (dihydroindolyl), isoindolyl, isoindolinyl, indazolyl, isobenzofuryl, 2,3-dihydrobenzofuryl, benzoxazolyl, benzoisoxazolyl, benzothiazolyl, ilo, benzimidazolyl, benzoxadiazolyl, benzothiadiazolyl, benzotriazolyl, purinyl, imidazopyridinyl, pyrazolopyridinyl, IF-2019-16742483-APN-ANP#INPI37 Page 37 of 402 triazolopyridinyl and 1,3-benzodioxolyl. Examples of 10-membered heteroaryl groups (6,6-fused heteroaryl) include quinolinyl (quinolyl), isoquinolyl, phthalazinyl, naphthyridinyl (1,5-naphthyridinyl, 1,6-naphthyridinyl, 1,7-naphthyridinyl, 1,8-naphthyridinyl) , quinazolinyl, quinoxalinyl, 4H-quinolizinyl, 1,2,3,4-tetrahydroquinolinyl (tetrahydroquinolinyl), 1,2,3,4-tetrahydroisoquinolinyl (tetrahydroisoquinolinyl), cinolinyl, pteridinyl, and 2,3-dihydrobenzo[b][l ,4]dioxin¡lo. The terms halogen and halo refer to a halogen radical, for example, a fluorine, chlorine, bromine or iodine substituent. Oxo represents an oxygen moiety with a double bond; For example, if it binds to a carbon atom it forms a carbonite residue (C=O). Hydroxy or hydroxyl refers to the -OH radical. As used herein, the term damage refers to a nitrile group, -ΟξΝ. As used herein, the term optionally substituted indicates that a group (such as an alkyl, cycloalkyl, alkoxy, heterocycloalkyl, aryl or heteroaryl group) or ring or moiety may be unsubstituted, or the group, ring or moiety may be substituted with one or more substituents as defined in the definitions of substituents (A, R3, etc.) provided herein. In cases where groups can be selected from a series of alternative groups, the selected groups can be the same or different. The term independently means that in cases where more than one substituent is selected from a series of possible substituents, these substituents may be the same or different. The term "pharmaceutically acceptable" refers to those compounds, materials, compositions, and dosage forms that are, within the scope of good medical judgment, suitable for use in contact with the tissues of humans and animals without toxicity, irritation, or other excessive problem or complication, provided with a reasonable benefit / risk ratio. As used herein, the terms compounds of the invention or compounds of the present invention mean a compound of formula (I-N), of formula (I) or of formula (I-P), as defined herein, in any form, that is, any tautomeric form, any isomeric form, any salt or non-salt form (for example, in the form of a free acid or base, or in the form of a salt, in particular a pharmaceutically acceptable salt of the themselves) and any physical form thereof (for example, including non-solid forms (for example, liquid or semi-solid forms), and solid forms (for example, amorphous or crystalline forms, specific polymorphic forms, forms of IF-2019-16742483-APN-ANP#INPI 38 Page 38 of 402 solvate, including hydrate forms (e.g., mono-, di-, and hemi-hydrates), and mixtures of various forms. Accordingly, the present invention includes compounds of formula (I-N), (I-P) or (I), as defined herein, in any salt or non-salt form and any physical form thereof and mixtures of various forms. Although these are included in the present invention, it will be understood that compounds of formula (I-N), (I-P) or (I), as defined herein, in any salt or non-salt form, and in any form physical properties of them, they can have different levels of activity, different bioavailabilities and different handling properties for formulation purposes. In one embodiment of the compounds of the present invention, R3 and R5 are each independently -CON(Rd)(Rf), or one of R3 and R5 is -CON(Rd)(Rf), and the other of R3 and R5 is H or -CO2( Rc). In one embodiment, R3 and R5 are each independently -CON(Rd)(Rf). In another embodiment, one of R3 and R5 is -CON(Rd)(Rf) and the other of R3 and R5 is H. In a specific embodiment, R3 and R5 are each -CONH2. It should be understood that when q is 0, A is absent and RA1 and RA2 are not connected. Similarly, it should be understood that when r is 0, B is absent and RB1 and RB2 are not connected. Similarly, it should be understood that when s is 0, C is absent and RC1 and RC2 are not connected. In one embodiment of the compounds of the present invention, q is 1, r is 0 and s is 0 (q+r+s= 1) and the compound has the formula (I-A) or (I-a): R4 In one embodiment of the compounds of the present invention, q is 0, r is 1 and s is 0 IF-2019-16742483-APN-ANP#INPI39 Page 39 of 402 (q+r+s=l) and the compound has the formula (I-B) or (I-b): In one embodiment of the compounds of the present invention, q is 0, r is 0 and s is 1 (q+r+s=l) and the compound has the formula (I-C) or (I-c): IF-2019-16742483-APN-ANP#INPI40 c) Page 40 of 402 In one embodiment of the compounds of the present invention, q is 1, r is 1 and s is 0 (q+r+s=2) and the compound has the formula (I-AB) or (I-ab): (I-ab) In one embodiment of the compounds of the present invention, q is 1, r is 0 and s is 1 (q+r+s=2) and the compound has the formula (I-AC) or (I-ac): IF-2019-16742483-APN-ANP#INPI41 Page 41 of 402 (I-AC) (I-ac) In one embodiment of the compounds of the present invention, q is 0, r is 1 and s is 1 (q+r+s=2) and the compound has the formula (I-BC) or (I-bc): In one embodiment of the compounds of the present invention, q is 0 and RA1 and RA2 are each independently H, halogen, hydroxy, -N(Re)(Rf), -CO2Rf, -N(Rf)CORb, -N(R9) SO2(C!-C4 alkyl)-N(Re)(Rf), -N(R9)CO(C1-C4 alkyl)-N(Rh)(Rf), (CrC6 alkyl) optionally substituted, (Ci-Cgjoxy alkyl - optionally substituted, (Ci-C6 alkyl)amino- optionally substituted, and (Ci-C6 alkyl)(Ci-C^alkyl)amino-optionally substituted, wherein the (Ci-C6 alkyl) of said (Ci-C6 alkyl) optionally substituted, (CrCg alkyl)oxy- optionally substituted, (optionally substituted CrCgjamino alkyl- and (optionally substituted Ci-C6 alkyl)(optionally substituted CrCOamino alkyl) is optionally substituted with 1-4 substituents each independently selected from hydroxyl, C1-C4 alkoxy -, -N(Re)(Rf), -CO2(Rf), -CON(Re)(Rf), optionally substituted phenyl, optionally substituted 5-6-membered heterocycloalkyl and an optionally substituted 5-6-membered heteroaryl group, wherein said optionally substituted phenyl, 5-6 membered heterocycloalkyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxy, amino, (Ci-C6 alkyl)amino-, (Ci-alkyl) CeXalkyl CrC6)amino-, IF-2019-16742483-APN-ANP#INPI 42 Page 42 of 402 halo(CrC6 alkyl), hydroxy-(C1-C4 alkyl)-, halo(Cj-G alkoxy)-, C1-C4 alkoxy-, hydroxy-(C2-C4 alkoxy)-, and CrC4 alkoxy- (C1-C4 alkoxy)-. In one embodiment of the compounds of the present invention, q is 0 and R and R are each independently H, halogen, hydroxy, -O-P(O)(OH)2, -OPtOXR'RHh, -N(ReXRf), -CO2Rf, -N(Rf)CORb, -N(R9)SO2(Crq alkyl)-N(Re)(Rf), -N(R9)CO(Ci-C4 alkyl)-N(Rh)(Rf), (Ci-C6 alkyl) optionally substituted, (CrCejoxy alkyl- optionally substituted, (Ci-Cejamino alkyl) optionally substituted, and (Ci-C6 alkyl) of said ( Ci-C6 alkyl) optionally substituted, (Ci-C6 alkyl)ox¡- optionally substituted, (optionally substituted Ci-QQamino alkyl- and (Ci-C6 alkyl)(optionally substituted Ci-CQamino alkyl- is optionally substituted with 1-4 substituents each independently selected from hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'Rn)2, Ci-C4-alkoxy, -N(Re)(Rf), -CO2(Rf), -CON(Re)(Rf), optionally substituted phenyl, 5-heterocycloalkyl 6-membered optionally substituted and an optionally substituted 5-6-membered heteroaryl group, wherein said optionally substituted phenyl, 5-6-membered heterocycloalkyl or 5-6-membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen , hydroxy, -O-P(O)(OH)2, -O-PIOXR'RHh, amino, (CrCejamino alkyl-, (Ci-C6 alkyl)(Ci-CeJamino alkyl-, (Ci-C6 alkyl)-NH2, halo (Ci-C6 alkyl), hydroxy-(C1-C4 alkyl)-, -(Ci-GO-OP(O)(OH)2 alkyl, -(Ci-CO-O-PIOXR'RHh alkoxy, halo(C1 alkoxy -C4)-, C1-C4 alkoxy-, hydroxy-(C2-C4 alkoxy)-, -(C2-C4 alkoxy)-O-P(O)(OH)2, -(C2-C4 alkoxy)-O-P(O) (RIRn)2, and alkoxy CrQXalkoxy CrQ)-. In one embodiment of the compounds of the present invention, q is 0 and RA1 and RA2 are each independently H, hydroxy, amino, (CrCOamino alkyl, (Ci-C4 alkyl)(Ci-C4 alkyl)amino-, (Ci-alkyl) CQ, hydroxy(C1-C0 alkyl-, amino(CrC4 alkyl)-, (Ci-C4 alkyl)amino(Ci-C alkyl)-, (Ci-Q alkyl)(Cj-COaminoyalkyl Ci-C»)- , Cj-Cr alkoxy, hydroxy(C2-C4 alkoxy)-, amino(C2-C4 alkoxy-CO-, (CrC4 alkyl)amino(C2-C4 alkoxy)-, (C2-C4 alkylCy-Qjaminoalkoxy) -, 6-membered heterocycloalkyl-(CrC4 alkyl)-, phenyl(Cj-Ci alkoxy)-, (Ci-Q alkyl)OCONH(Ci-C4 alkyl)-, hydroxy(Ci-C^alkyl)-, (Ci-C4 alkyl)CONH-, (Ci-C alkyl^CONtalkyl Ci-CQ-, -CO2H, -CO2(Cj-G alkyl,), amino(CrC4 alkyl)CONH-, (Ci-CO alkylaminotalkyl Ci-COCONH -, (alkyl Cj-QXalkyl Cr^aminoalkyl IF-2019-16742483-APN-ANP#INPI 43 Page 43 of 402 Ci-C4)CONH-, amino(Ci-C4 alkyl)CON(Ci-Q alkyl)-, (Ci-C4 alkyl)amino(CrC4 alkyl)CON(C1-C4 alkyl)-, hydroxy(Ci-alkyl)- C^CONH-, (Ci-CtalkylCj-C^aminoCalkyl Ci-C,)CON(C1-C4 alkyl)-, hydroxy(Ci-QjalkyCONÍCpC alkyl,)-, HO2C(CpG alkoxy,)-, ( C!-Q alkyl)OCO(C1-C4 alkoxy)-, H2NCO(Cj-Q alkoxy)-, (Cj-CQHNCiXCi-C4 alkyl)-, (Ci-C4 alkyl)(Ci-C4 alkyl) NCO(alkoxy¡ Cj-C^)-, and -NHSO2(alkyl Ci-Cj). In one embodiment of the compounds of the present invention, q is 0 and R and R are each independently H, hydroxy, -O-P(O)(OH)2, -Ο-Ρ(Ο)(^Π)2, amino , (CrCOaminoalkyl-, (Ci-GiXalkylCi-C4alkyl)amino-, (CpC alkyl,), hydroxy(Ci-C^alkyl)-, amino(C1-CQ-alkyl-, (Cr^aminoalkylCi-C ^)-, (Ci-C alkyl^XCi-COaminotalkyl CpC alkyl,)-, Ci-C alkoxy»-, hydroxy(CrC alkoxy,)-, -(C2-C4 alkoxy)-O-P(O)(OH)2 , (alkoxy CrCO-O-PIOXR^)^ amino(alkoxy¡ C2·^)-, (alkyl Ci-C4)amino(alkoxy¡ C2-C4)-, (alkyl Ci-Cjjálkyl Ci-C4)amino(alkoxy¡ C2·^)-, 6-membered heterocycloalkyl-(Ci-C4 alkyl)-, phenyl(alkoxy(ΙΛ)-, (CrQOCONHYalkylCrC4 alkyl)-, hydroxy(Ci-C^alkyl)-, amino (alkyl C!-C4)-O-P(O)(OH)2, -amino(alkyl Ci-QFO-PIOXR'r)^ (alkyl Ci-CQCONH-, (alkyl CrCOCONtalkyl Cj-Q)-, -CO2H, - CO2(Q-Q alkyl), amino(Ci-Q alkyl)CONH-, (Ci-C4 alkyl)amino(Ci-CQ alkylCONH-, (CpQalkylCi-Qaminoalkyl CrCOCONH-, amino(Ci-CXjCONÍalkylCpC,)-, (Ci-C4 alkyl)amino(Ci-C4 alkyl)CON(Ci-C alkyl)-, hydroxy(Ci-C4 alkyl)-, -NHCO(Ci-C4 alkyl)-O-P(O)(OH)2, - NHCO(Ci-CO-O-PIOXR'R11 alkyl)^ (Ct-C4 alkyl)(CrC alkyl^aminotalkyl Ci-CjjCONÍC1-C4 alkyl)-, hydroxy(Ci-COCONÍalkyl Ci-C»)-, -(alkyl Ci-^NCOÍalkyl Ci-Q)-O-P(O)(OH)2, -(alkyl CrCONCOÍalkyl Ci-Qj-O-PÍOJÍR'R1^, HO2C(alkoxy¡ CrQ-, (alkyl Ci-COOCCXalkoxy Ci-C,) -, H2NCO(Ci-C» alkoxy)-, (Cj-C4 alkyl)HNCO(Ci-C» alkoxy)-, (CrQalkyl Ci-C4 alkyl)NCO(Q-Q alkoxy-, and -NHSO2(Q-C alkyl,) . In one embodiment, q is 0 and RA1 and RA2 are each independently H, (CrC6 alkyl)ox¡- or hydroxy(C2-C6 alkyl)ox¡-. In one embodiment, q is 0 and RA1 and RA2 are each independently H, (Ci-Cg alkyl)ox¡-, hydroxy(C2-Cg alkyl)oxy-, -(alkoxy 62-04)-0-Ρ(0)( 0Η)2, -(alkoxy CrGO-O-PIOXR'R11);,. In one embodiment, q is 0 and RA1 and RA2 are each H. In selected embodiments, q is 0 and RA1 and RA2 are independently selected from H, -OCH2CH2CH2OH and -OCH3. In one embodiment, q is 0 and RA2 and RA1 are each independently H, (CrCg alkyl) optionally substituted, or (CrCg alkyl)ox¡- optionally substituted, wherein the Ci-Cg alkyl of said (Q-Cg alkyl) optionally substituted, or optionally substituted (alkyl CrC6)ox¡- is optionally substituted with 1-4 substituents each independently selected from the group consisting of hydroxyl, -O-P(O)(OH)2, -O-PIOXR'R11)^ IF-2019-16742483-APN-ANP#INPI44 Page 44 of 402 C1-C4 alkoxy, -N(Re)(Rf), -COOH, optionally substituted phenyl, and optionally substituted 5-6 membered heterocycloalkyl, and each Rese independently selected from H, C1-C4 alkyl, -CO (C1-C4 alkyl), -OCO(C1-C4 alkyl), -(Ci-C4 alkyl)NH2, -(C1-C4 alkyl) C1-C4 alkoxy, or -CO2(C1-C4 alkyl). In one embodiment, q is 0 and RA2 and RA1 are each independently H, (CiC& alkyl) optionally substituted, or (Ci-Cejoxy-alkyl) optionally substituted, and the Cj-Ce alkyl of said (CrC6 alkyl) optionally substituted, (CrC6 alkyl optionally substituted )oxy- is optionally substituted with 1-4 substituents each independently selected from the group consisting of hydroxyl, -O-P(O)(OH)2, -Ο-Ρ(ΟΧ^Π)2, -N(Re )(Rf), C1-C4 alkoxy, phenyl, and optionally substituted 5-6 membered heterocycloalkyl containing at least one nitrogen or oxygen as a ring member, and each Rese independently selected from H, C1-C4 alkyl, (C1-C4 alkyl, Ci-C4)NH2, or -(Ci-COalkoxy C1-C4 alkyl. In one embodiment, q is 0 and at least one of RA2 or RA1 are each independently H, (optionally substituted Ci-C6 alkyl), or (optionally substituted Ci-QO alkyl, and the CrCe alkyl of said optionally substituted (Ci-Ce alkyl). , optionally substituted (CrC6 alkyl)oxy- is optionally substituted with 1-4 substituents independently selected from -N(Re)(Rf), tetrahydropyran, pyrrolidinyl, piperazinyl, piperidyl and morpholinyl and each Rese independently selected from H, C1-C4 alkyl , (Ci-C4 alkyl)NH2, or -(Cj-C alkyl^C1-C4 alkoxy. In one embodiment, q is 0 and at least one of RA2 or RA1 are each independently H, (optionally substituted Ci-C6 alkyl), or (optionally substituted Ci-QO alkyl, and the Ci-Ce alkyl of said (Ci-Cg alkyl) optionally substituted, optionally substituted (Ci-C6 alkyl)oxy- is optionally substituted with 1-4 substituents independently selected from tetrahydropyran, pyrrolidinyl, piperazinyl, piperidyl and morpholinyl, and each Rese independently selected from H or CpC^ alkyl. In one embodiment of the compounds of the present invention, r is 0 and R and R are each independently H, optionally substituted Ci-Ce alkyl, halo(Ci-Ce alkyl), optionally substituted C2-Cg alkenyl, optionally substituted C2-C6 alkynyl. substituted, optionally substituted C3-C6 cycloalkyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-10 membered heteroaryl, wherein said optionally substituted Ci-Ce alkyl , optionally substituted C2-Ce alkenyl, optionally substituted C2-Ce alkynyl, optionally substituted C3-C6 cycloalkyl, optionally substituted 4-6 membered heterocycloalkyl, phenyl IF-2019-16742483-APN-ANP#INPI 45 Page 45 of 402 optionally substituted, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-10 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, nitro, -Rc, -OH, -ORC , -NH2, -NRCRC, -NRcRd, -OCORc, -CO2H, -CO2Rc, -SORC, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, - NRdCO2Rc, and -NRdSO2Rc. In one embodiment, r is 0 and RB1 and RB2 are each H. In another embodiment, r is 0 and RB1 and RB2 are each independently optionally substituted 6-membered, optionally substituted 5-6-membered heteroaryl or optionally substituted 9-membered heteroaryl. In one embodiment of the compounds of the present invention, s is 0 and RC1 is H, halogen, or Ci-C4 alkyl and RC2 is optionally substituted Ci-Cj alkyl, wherein said optionally substituted CrC4 alkyl group is optionally substituted with a substituent selected from - ORC, -NRcRd, -CO2Rc, -CONRcRd, -SO2NRcRd, and -OCONRcRd. f Cl C2 In one embodiment of the compounds of the present invention, when s is 0, R and R are each independently H or Cj-C4 alkyl. In another embodiment, when s is 0, RC1 is CrC3 alkyl, specifically methyl. In another embodiment, when s is 0, RC2 is CrC3 alkyl, specifically methyl or ethyl. In a selected embodiment, when s is 0, Rc2 is ethyl. In one embodiment of the compounds of the present invention, q is 1 and RA1 and RA2 are each independently -CH2-, -NRe-, or -O-, and A, taken together with RA1 and RA2, forms a linker group, where A is -halo(Cj-C^alkyl)-, -Ci-Ci2-alkyl- optionally substituted, C2-Ci2-alkenyl- optionally substituted, C2-Ci2-alkynyl- optionally substituted, -Cj-Cg-O-alkylCrC6-alkyl- optionally substituted , -Ci-C6-NRa-alkyl-CrC6-alkyl- optionally substituted, -CfCe-alkyl-C3-C6-Ccycloalkyl)-CrC6-alkyl- optionally substituted, -Ci-C6-alkyl-phenyl-Cj-Ce-alkyl- optionally substituted, -CrC6-alkyl -(4-6-membered heterocycloalkyl)-optionally substituted Cj-Cg-alkyl, or -optionally substituted -CrC6-alkyl-(5-6-membered heteroaryl)-optionally substituted Ci-C6-alkyl, wherein the alkyl moiety of said -Cj-alkyl -Ci2- optionally substituted, C2-Ci2-alkenyl optionally substituted, C2-Ci2-alkynyl optionally substituted, -Ci-C6-alkyl-O-Ci-C6-alkyl- optionally substituted, -Ci-C6-alkyl-NRa-Ci-C6-alkyl - optionally substituted, -Ci-C6 alkyl-(C3-C6 cycloalkyl)-CrCe alkyl- optionally substituted, -Ci-C6 alkyl-phenyl-CpCe alkyl- optionally substituted IF-2019-16742483-APN-ANP#INPI46 Page 46 of 402 substituted, -Ci-C6-alkyl-(4-6-membered heterocycloalkyl)-alkyl Ci-Ce- optionally substituted, or -CrC6-alkyl-(5-6-membered heteroaryl)-optionally substituted Ci-C6-alkyl is optionally substituted by 1-4 substituents each independently selected from halogen, halo(C1-C4 alkyl) , -OH, -ORC, -NH2, -NRcRd, -OCORc, -CO2H, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcR d -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc, and the C3-C6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said -Ci-C6 alkyl-(C3-C6 cycloalkyl)-optionally substituted Ci-C6 alkyl, -Ci-alkyl C6-phenyl-Ci-C6-alkyl-optionally substituted, -Ci-C6-alkyl-(4-6-membered heterocycloalkyl)-optionally substituted Ci-C6-alkyl, or -CrC6-alkyl-(5-6-membered heteroaryl) members)-optionally substituted CrC6-alkyl is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, amino, (Ci-COamino-alkyl, (Ci-C4-alkyl)(Ci-Qamino-alkyl, CrC-alkyl, , halo(Q-C4 alkyl), halo(Ci-C4 alkoxy)-, C1-C4 alkoxy-, hydroxy-(C2-C4 alkoxy)-, and Ci-CX alkoxyCi-C4 alkoxy)-. In one embodiment of the compounds of the present invention, q is 1 and RA1 and RA2 are each independently -CH2-, -NRe-, or -O-, and A, taken together with RA1 and RA2, forms a linker group, where A is -halo(Ci-Ci2 alkyl)-, -CrCi2-alkyl- optionally substituted, C2-Ci2-alkenyl optionally substituted, C2-Cj2-alkyl- optionally substituted, -Ci-Ce-O-alkyl-Ci-C6-alkyl- optionally substituted, -Ci-C6-alkyl-NRa-CrC6-alkyl- optionally substituted, -Ci-C6-alkyl-(C3-C6 cycloalkyl)-Ci-Ce-alkyl- optionally substituted, -Ci-C6-alkyl-phenyl-Ci-C6-alkyl- optionally substituted , -Ci-C6-alkyl-(4-6-membered heterocycloalkyl)-optionally substituted Ci-C6-alkyl, or -optionally substituted-Ci-C6-alkyl-(5-6-membered heteroaryl)-Ci-C6-alkyl, wherein the alkyl moiety of said -CrCi2-alkyl- optionally substituted, C2-Ci2-alkenyl optionally substituted, C2-Ci2-alkynyl- optionally substituted, -Ci-C6-alkyl-O-CrC6-alkyl- optionally substituted, -CrC6-alkyl-NRa- CrC6-alkyl- optionally substituted, -Ci-C6-alkyl-(C3-C6 cycloalkyl)-CrC6-alkyl- optionally substituted, -Ci-C6-alkyl-phenyl-Ci-Cg-alkyl- optionally substituted, -Ci-C6-alkyl-(heterocycloalkyl) 4-6 members)-alkyl Ci-Ce- optionally substituted, or -Ci-C6-alkyl-(5-6-membered heteroaryl)-optionally substituted Ci-C6-alkyl is optionally substituted by 1-4 substituents IF-2019-16742483-APN-ANP#INPI 4? Page 47 of 402 each independently selected from halogen, halo(Ci-C4 alkyl), -OH, -O-P(O)(OH)2, -O-P(O)(RiRn)2, -ORc, -NH2, -NRcRd, -OCORc, -CO2H, -CO2Rc, -SORC, -SO2RC, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, - OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc, and the C3-C6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said -Ci-Cg alkyl-fC3-Ce cycloalkyl)-Ci-C6 alkyl- optionally substituted, -Ci-C6 alkyl -phenyl-Ci-C6-alkyl- optionally substituted, -Ci-C6-alkyl-(4-6-membered heterocycloalkyl)-optionally substituted Ci-C6-alkyl, or -CrC6-alkyl-(5-6-membered heteroaryl)-Ci-alkyl optionally substituted -Cg- is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -Ο-Ρ(Ο)^^Π)2, amino, (alkyl Ci -GOamino-, (Ci-CjalkylCi-C^alkyl^amino-, CrC4 alkyl, halo(Ci-Q alkyl), halo(Ci-CO alkoxy, Ci-Cp alkoxy, hydroxy-(C2·^ alkoxy) -, -(alkoxy CrCO-O-PIOXOHh, -(alkoxy CrqyO-PtOXR^h, and alkoxy Cj-CHalcoxj Ci-C,)-. In one embodiment, q is 1 and A, taken together with RA1 and RA2, forms a 4-8 member linker group. In a further embodiment, q is 1 and A, taken together with RA1 and Ra2, forms a 4-6 member linker group. In yet another embodiment, q is 1 and A, taken together with RA1 and RA2, forms a 5-member linker group. In another embodiment, q is 1, RA1 and RA2 are each independently -CH2-, -NRe-, or -O-, and A is a substituted -C2-Ci0-alkyl- group or is a -C2-Ci0-alkyl- group, - C2-Ci0 alkenyl, -C2-Ci0 alkynyl, -Cj-C4 alkyl-O-CpCr alkyl, or -Ci-CpNRa alkyl-Ci-Cj alkyl- unsubstituted, said group being -C2-Ci0 alkyl- substituted, substituted with 1-4 substituents each independently selected from halogen, hydroxy, amino, (Ci-COamino-alkyl, (Ci-C4alkylxXCi-C4alkyl)amino-, halo(CrC4alkyl), halo(Ci-C4alkoxy)- , and Ci-Cp alkoxy. In another embodiment, q is 1, RA1 and RA2 are each independently -CH2-, -NRe-, or -O-, and A is a substituted -C2-Ci0-alkyl- group or is a -C2-Cio-alkyl- group, - C2-Ci0 alkenyl-, -C2-Ci0 alkynyl-, -Ci-CpO alkyl-Ci-Q alkyl-, or -CrQ-NRa alkyl-Q-Ci alkyl- unsubstituted, said group being -C2-Cio alkyl- substituted , substituted with 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -0P(O)(R!Rn)2, amino, (alkyl Ci-COamino-, (alkyl Cj -qXalkyl Cj-^amino-, halo(CpC alkyl), halo(Ci-Ch alkoxy)-, and Ci-C»-alkoxy-. IF-2019-16742483-APN-ANP#INPI 48 Page 48 of 402 In another embodiment, q is 1, RA1 and RA2 are each independently -CH2-, -NRe-, or -O-, and A is a substituted -C2-C8-alkyl- group or is a -C2-C8-alkyl- group, - C2-C8 alkenyl-, -C2-C8 alkynyl-, -C2-C2 alkyl-O-CrC2 alkyl-, or -C2-C2 alkyl-NRa-CrC2 alkyl- unsubstituted, said group being -C2-C8 alkyl- substituted , substituted with 1-2 substituents each independently selected from halogen, hydroxy, amino, (alkyl Ci-COamino-, (alkyl CrC4)(alkyl Ci-C^amino-, halo(alkyl CrQ), halo(alkoxy¡ Ci- Q)-, and alkoxy Oj-Cr. In another embodiment, q is 1, RA1 and RA2 are each independently -CH2-, -NRe-, or -O-, and A is a substituted -C2-C8-alkyl- group or is a -C2-C8-alkyl- group, - C2-C8 alkenyl-, -C2-C8 alkynyl-, -Cj-C2 alkyl-O-Cj-C2 alkyl-, or -Ci-C2 alkyl-NRa-Cj-C2 alkyl- unsubstituted, said group being -C2 alkyl -C8- substituted, substituted with 1-2 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -Ο-Ρ(Ο)^^Π)2, amino, (alkyl Ci-COamino -, (Cj-QalkylCi-C^amino-alkyl, halo(CpC alkyl), halo(CpC alkoxy)-, and Ci-Cp alkoxy. In another embodiment, q is 1, RA1 and RA2 are each independently -CH2-, -NRe-, or -O-, and A is a substituted -C2-C6-alkyl- group or is a -C2-Ce-alkyl- group, - C2-C6 alkenyl-, -C2-Cg alkynyl-, -Ci-C2 alkyl-O-Cj-C2 alkyl-, or -C2-C2 alkyl-NRa-Ci-C2 alkyl- unsubstituted, said group being -C2 alkyl -Ce- substituted, substituted with 1-2 substituents each independently selected from halogen, hydroxy, amino, (alkyl CrQjamino-, (alkyl Ci-CQfalkyl Ci-Cjjamino-, halo(alkyl Cj-Gj), halo(alkoxy¡ Ci -C,)-, and alkoxy Ci-C,-. In another embodiment, q is 1, RA1 and RA2 are each independently -CH2-, -NRe-, or -O-, and A is a substituted -C2-C8-alkyl- group or is a -C2-C8-alkyl- group, - C2-C8 alkenyl-, -C2-C6 alkynyl-, -Ci-C2 alkyl-O-Cj-C2 alkyl-, or -CrC2-NRa alkyl-CrC2 alkyl- unsubstituted, said group being -C2-Cg alkyl- substituted , substituted with 1-2 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -Ο-Ρ(Ο)^^Π)2, amino, (Ci-C4 alkyl)amino-, (CrC alkylCrQamino-alkyl, halo(CrQ alkyl), halo(Ci-C alkoxy)-, and CrC4 alkoxy-. In another embodiment, q is 1, RA1 and RA2 are each independently -CH2- or -O-, and A is a -CrCr alkyl, -C2·^-alkenyl, or -GC-alkynyl- group. In selected embodiments, q is 1, RA1 and RA2 are each -O-, and A is -CH2CH2CH2-, where A, taken together with RA1 and RA2, forms a group -OCH2CH2CH2O-. In another embodiment, q is 1, RA1 and RA2 are each -O-, and A is -CH2-phenyl-CH2-, where A, taken together with RA1 and RA2, forms a group -OCH2-phenyl-CH2O-. In a specific embodiment, q is 1, A, taken together with RA1 and RA2, forms a -OCH2-phenyl-CH2O- group, wherein the -OCH2- groups are located at 1, 4 on the phenyl ring moiety. The length of the linker groups defined herein represents the smallest number of atoms in a direct chain composed of -RA1-A-RA2- and / or -Rb1-B-Rb2- and / or IF-2019-16742483-APN-ANP#INPI49 Page 49 of 402 -Rci-C-Rc2-. For example, when B is an optionally substituted phenyl, the linker group -Rb1-B-Rb2- may be represented as -(CH2)-phenyl-(CH2)-. This linker group is characterized as a 4-membered linker group when the 2 -(CH2) residues are located on adjacent carbon atoms of the phenyl ring (1,2-substituted phenyl). In another embodiment, this linker group is characterized as a 6-member linker group when the 2 residues -(CH2)- are substituted at para positions on the phenyl ring (1,4 substituted phenyl). Any alkyl, alkenyl or alkynyl group or residue of A, B or C will be understood to be a linear or branched alkyl, alkenyl or alkynyl group or residue. For example, a linker group -Rb1-B-Rb2-, where B is -Cj-Cio alkyl- may contain an 8-member linker group that has one branching group (C1-C4 alkyl) or 2-4 branching groups ( C1-C3 alkyl), for example, 4 methyl branching groups (2 gem-dimethyl groups) or 2 methyl branching groups. In one embodiment of the compounds of the present invention, r is 1 and RB1 and RB2 are each independently -CH2-, and B, taken together with RB1 and RB2, forms a linker group, where B is a bond or B is -halo( C1-C10 alkyl)-, -C1-C10 alkyl- optionally substituted, C2-Ci0 alkenyl- optionally substituted, C2-Cio-alkynyl optionally substituted, -Ci-C6-alkyl-O-Ci-C6 alkyl- optionally substituted, -alkyl CrCe-NRa-optionally substituted Ci-Ce-alkyl, optionally substituted C3-Ce cycloalkyl, optionally substituted phenyl, optionally substituted 4-6-membered heterocycloalkyl, optionally substituted 5-6-membered heteroaryl, -CrC4-alkyl-(C3-C6 cycloalkyl )-optionally substituted Ci-C4-alkyl, -optionally substituted -Ci-Crphenyl-alkyl-CrQ-alkyl, -optionally substituted 4-6-membered Ci-C-alkylheterocycloalkyl)-optionally substituted Ci-Cp-alkyl, or -5-membered -Ci-Crtheteroaryl alkyl 6 membered) -C1-C4-alkyl- optionally substituted, wherein the alkyl moiety of said -C1-C10-alkyl- optionally substituted, C2-Cio-alkenyl- optionally substituted, C2-Cio-alkynyl- optionally substituted, -Ci-C6-alkyl- O-Ci-C6-alkyl-optionally substituted, -Ci-C6-alkyl-NRa-Ci-C6-alkyl-optionally substituted, -Ci-CHalkylcycloalkylC3-C6)-optionally substituted CrCr-alkyl, -CrQ-alkyl-phenyl-alkyl C1-C4- optionally substituted, -Cj-alkyl-4-6-memberedCryheterocycloalkyl)-optionally substituted Ci-Cr-alkyl, or -Cr-alkylCryheteroaryl5-6-membered-Ci-C4-alkyl)- optionally substituted is optionally substituted with 1 or 2 substituents each independently selected from halogen, halo(Cj-C»alkyl), -OH, -ORC, -NH2, -NRcRd, -OCORc, -CO2H, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd , -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRCR d / -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc, IF-2019-16742483-APN-ANP#INPI50 Page 50 of 402 the moiety C3-C6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl or 5-6 membered heteroaryl of said optionally substituted C3-C6 cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, 5-membered heteroaryl -6 members optionally substituted, -Ci-C4 alkyl-(C3-C6 cycloalkyl)-C1-C4 alkyl- optionally substituted, -Ci-C4 alkyl-phenyl-C1-C4 alkyl- optionally substituted, -Ci-C4 alkyl-( 4-6 membered heterocycloalkyl)-optionally substituted CrCr alkyl, or -5-6 membered Ci-Crtheteroaryl alkyl)-optionally substituted Ci-C4-alkyl is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, amino, (Ci-C alkyl^amino-, (CrC alkyl^Xalkyl CrCOamino-, Ci-Cj alkyl, halo(C1-C0 alkyl, halo(Cj-C^ alkoxy)-, Ci-Cr alkoxy, hydroxy-(alkoxy ¡ C2-CO-, and alkoxy Ci-Críalkoxy Ci-C4)-. In one embodiment of the compounds of the present invention, r is 1 and RB1 and RB2 are each independently -CH2-, and B, taken together with RB1 and RB2, forms a linker group, where B is a bond or B is -halo( C1-C10 alkyl)-, -CrCio-alkyl- optionally substituted, C2-Cio-alkenyl- optionally substituted, C2-C10-alkynyl- optionally substituted, -CrC6-alkyl-O-Ci-C6-alkyl- optionally substituted, -CrC6-alkyl-NRa- optionally substituted Ci-C6-alkyl, optionally substituted C3-Cg cycloalkyl, optionally substituted phenyl, optionally substituted 4-6-membered heterocycloalkyl, optionally substituted 5-6-membered heteroaryl, -optionally substituted CrCtXcycloalkyl)-optionally substituted Ci-Cr alkyl substituted, -Cy-C4 alkyl-phenyl-CpCr alkyl optionally substituted, -Cj-alkyl-Cryheterocycloalkyl of 4-6 members)-alkyl Cj-C4- optionally substituted, or -Cy-C4 alkyl-(5-6 membered heteroaryl) -optionally substituted Ci-Cp alkyl, wherein the alkyl moiety of said -optionally substituted C1-C10 alkyl, optionally substituted C2-Cio alkenyl, optionally substituted C2-C10 alkynyl, -Cj-Cg-O-Ci alkyl -C6- optionally substituted, -Ci-C6-NRa-alkyl Ci-C6- optionally substituted, -CrC4 alkyl-(C3-C6 cycloalkyl)-optionally substituted CpCr alkyl, -Ci-C4 alkyl-phenyl-Ci-C4 alkyl- optionally substituted, -CrC4 alkyl-(4-6 membered heterocycloalkylj -I rent optionally substituted Ci-Cp, or -optionally substituted -5-6-membered Ci-Cryheteroaryl-alkyl-CpCi)-alkyl is optionally substituted with 1 or 2 substituents each independently selected from halogen, halo(Cj-C4 alkyl), -OH, -O-P(O)(OH)2, -O-PÍOjí^R11)^ -ORC, -NH2, -NRcRd, -OCORc, -CO2H, -CO2Rc, -SORC, -SO2RC, -CONH2, -CONRcRd, -SO2N IF-2019-16742483-APN-ANP#INPI51 Page 51 of 402 H2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc, and the C3-C6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl or 5-6 membered heteroaryl moiety of said cycloalkyl C3-C6 optionally substituted, phenyl optionally substituted, 4-6 membered heterocycloalkyl optionally substituted, 5-6 membered heteroaryl optionally substituted, -Ci-C4 alkyl-(C3-C6 cycloalkyl)-C1-C4 alkyl- optionally substituted, -Ci-Gj-alkyl-phenyl-C1-C4-alkyl- optionally substituted, -Ci-C4-alkyl-(4-6-membered heterocycloalkyl)-C,-C4-alkyl- optionally substituted, or -Ci-Cr-alkylCheteroaryl -6-membered)-alkylCrC,- optionally substituted is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -Ο-Ρ(Ο)(^π)2 , amino, (Ci-C^amino-alkyl, (Cj-COAlkylCi-C^amino-alkyl, C1-G1 alkyl, halo(Cj-C alkyl), halo(CrQ alkoxy)-, Cj-Gr alkoxy, hydroxy-(C2-C4 alkoxy)-, and CrQXalkoxy Ci-C,)-. In one embodiment of the compounds of the present invention, r is 1, RB1 and RB2 are each independently -CH2-, and B, taken together with RB1 and RB2, forms a 2-6 member linker group. In a further embodiment, r is 1, RB1 and RB2 are each independently -CH2-, and B, taken together with RB1 and RB2, forms a 3-6 member linker group. In yet another embodiment, r is 1, RB1 and RB2 are each independently -CH2-, and B, taken together with RB1 and RB2, forms a 4-5 member linker group. In one embodiment, B is a link. In another embodiment, r is 1, RB1 and RB2 are each independently -CH2-, and B is a substituted -C1-C10-alkyl- group or is a -C1-C10-alkyl-, -C2-C,o-alkenyl- group, - C2-C10-alkynyl-, -Ci-C6-alkyl-O-Ci-C6-alkyl-, or -Ci-C6-alkyl-NRa-Q-Ce-alkyl- unsubstituted, said group being -Q-Cio-alkyl- substituted, substituted with 1-4 substituents each independently selected from halogen, hydroxy, amino, (CrCeJamino-alkyl), (Ci-Ce alkyl)(Ci-C6 alkyl)amino-, halo(Ci-C6 alkyl), halo(C1 alkoxy -C4)-, Cj-C4 alkoxy-, hydroxy-(C2-C4 alkoxy)-, Cj-CH alkoxyCj-C alkoxy,)-, -NHCO(Ci-Q alkyl), optionally substituted phenyl, 5-6 heterocycloalkyl optionally substituted member and optionally substituted 5-6 membered heteroaryl, wherein said optionally substituted phenyl, 5-6 membered heterocycloalkyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxy, amino, (CrC6 alkyl)amino-, (Ci-C6 alkyl)(CrC6 alkyl)amino-, halo(Ci-CJ alkyl, halo(Ci-C4 alkoxy)-, IF-2019-16742483-APN-ANP#INPI52 Page 52 of 402 C1-C4 alkoxy-, hydroxy-(C2-C4 alkoxy)-, and CrCr alkoxy(C1-C4 alkoxy)-. In another embodiment, r is 1, RB1 and RB2 are each independently -CH2-, and B is a substituted -CrCi0-alkyl- group or is a -C1-C10-alkyl-, -C2-Ci0-alkenyl-, -C2-C10-alkynyl group. -, -CrQ alkyl-O-Ci-C6 alkyl-, or -CrC6 alkyl-NRa-CrQ alkyl- unsubstituted, said group -C1-C10 alkyl- being substituted, substituted with 1-4 substituents each independently selected from halogen , hydroxy, -O-P(O)(OH)2, -Ο-Ρ(Ο)(^π)2, amino, (Ci-C6 alkyl)amino-, (Ci-C6 alkyl)(CrQamino alkyl-, halo( CpCe alkyl), halo(C1-C4 alkoxy)-, C1-C4 alkoxy-, hydroxy-(CrC alkoxy)-, Ci-C4 alkoxy-(C1-C0 alkoxy-, -NHCO(Ci-C alkyl) , optionally substituted phenyl, optionally substituted 5-6 membered heterocycloalkyl and optionally substituted 5-6 membered heteroaryl, wherein said optionally substituted phenyl, 5-6 membered heterocycloalkyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -O-PIOXR'R11)2, amino, (Ci-C6 alkyl)amino-, (Ci-C6 alkyl)(Ci-alkyl) Qamino-, halo(Ci-C6 alkyl), halo(Ci-C alkoxy)-, Ci-Gr alkoxy, hydroxy-(Cz-C» alkoxy)-, and CrCiXalkoxy Ci-q)-. In another embodiment, r is 1, RB1 and RB2 are each independently -CH2-, and B is a -substituted Ci-Cw alkyl group or is a -C1-C10 alkyl-, -C2-C10 alkenyl-, -C2 alkynyl- group. Ci0-, -Ci-C6-alkyl-O-Ci-C6-alkyl-, or -Ci-Ce-NRa-alkyl-CpCg-alkyl- unsubstituted, said group being -Ci-Cw-alkyl- substituted, substituted with 1-4 selected substituents each independently between halogen, hydroxy, amino, (alkyl Ci-C^amino-, (alkyl CrC^Xalkyl Ci-C^amino-, halo(alkyl Ci-Q), halo(alkoxy¡ Cj-Ch)-, and alkoxy Ci-C4-. In another embodiment, r is 1, RB1 and RB2 are each independently -CH2-, and B is a substituted -CrCi0-alkyl- group or is a -Ci-Ci0-alkyl-, -C2-Ci0-alkenyl-, -C2-C10-alkynyl group. -, -CrC6-alkyl-O-Ci-C6 alkyl-, or -Ci-C6 alkyl-alkyl-, unsubstituted, said group being -CpCio-alkyl- substituted, substituted with 1-4 substituents each independently selected from halogen , hydroxy, -O-P(O)(OH)2, -Ο-Ρ(Ο)(Β^π)2, amino, (CpC^alkyl^amino-, (Ci-C4alkyl)(Ci-Qaminoalkyl-, halo (Ci-CO alkyl, halo(alkoxy, CrC4)-, and Cj-C4 alkoxy-. In another embodiment, r is 1, RB1 and RB2 are each independently -CH2-, and B is a substituted -Ci-C8 alkyl- group or is a -Ci-C8 alkyl-, -C2-C8 alkenyl-, -C2 alkynyl group. -C8-, -Ci-Gi-O-alkyl-CpCr-alkyl, or -Cj-C4-NRa-alkyl-Oj-C-alkyl,- unsubstituted, said group being -Ci-C8-alkyl- substituted, substituted with 1-4 substituents each independently selected from halogen, hydroxy, amino, (Ci-C alkyl^amino-, (CrQX alkyl Ci-COamino alkyl-, halo(Ci-CO alkyl, halo(CrC alkoxy)-, and C1-C4 alkoxy-. In another embodiment, r is 1, RB1 and RB2 are each independently -CH2-, and B is a IF-2019-16742483-APN-ANP#INPI 53 Page 53 of 402 substituted -CrC8-alkyl- group or is a group -Ci-C8-alkyl-, -C2-C8-alkenyl-, -C2-C8-alkynyl-, -Ci-CrO-alkyl-CpCp-alkyl, or -CpCí-alkyl-NR '-C1-C4-alkyl- unsubstituted, said -CpC8-alkyl- group being substituted, substituted with 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -Ο-Ρ(ΟΧ^Π)2, amino, (CpCOamino alkyl-, (Ci-C4 alkyl)(Ci-GQamino alkyl-, halo(C1-C4 alkyl), halo (CpQ alkoxy)-, and C1-C4 alkoxy-. In another embodiment, r is 1, RB1 and RB2 are each independently -CH2-, and B is a substituted -Ci-C6 alkyl- group or is a -CpCg alkyl-, -C2-C6 alkenyl-, -C2-C6 alkynyl group. -, -Ci-C2-O-alkyl-Ci-C2-alkyl-, or -Ci-C2-alkyl-NRa-CpC2-alkyl- unsubstituted, said group being -Ci-C6-alkyl- substituted, substituted with 1-2 substituents each selected one independently of halogen, hydroxy, amino, (CpC4 alkyl)amino-, (CpC4 alkyl)(Ci-C^amino alkyl-, halo(CpC4 alkyl), halo(CpC4 alkoxy)-, and CpCp alkoxy. In another embodiment, r is 1, RB1 and RB2 are each independently -CH2-, and B is a substituted -Ci-C6 alkyl- group or is a -CpCe alkyl-, -C2-C6 alkenyl-, -C2-C6 alkynyl group. -, -Ci-C2-O-alkyl-CpC2-alkyl-, or -unsubstituted -CpC2-alkyl-NRa-CpC2-alkyl-, said group being substituted -CrC6-alkyl-, substituted with 1-2 substituents each independently selected from halogen, hydroxy , -O-P(O)(OH)2, -Ο-Ρ(ΟΧ^Π)2, amino, (Ci-C4 alkyl)amino-, (CpCj alkylCpCOamino-alkyl-, halo(CpC alkyl»), halo(CpCj alkoxy )-, and alkoxy CpCp. In another embodiment, r is 1, RB1 and RB2 are each independently -CH2-, and B is a substituted -C2-C4-alkyl- group or is a -C2-C4-alkyl-, -C2-C4-alkenyl-, -C2-alkynyl- group. C4-, -Ci-O-alkyl-Cp alkyl or -CrNRa alkyl-unsubstituted Cp alkyl, said group being -C2-C4-alkyl- substituted, substituted with 1-2 substituents each independently selected from halogen, hydroxy, amino, ( alkyl CpCOamino-, (alkyl CpCjXalkyl CpCOamino-, halo(alkyl CpCO, halo(alkoxy¡ CpC,)-, and alkoxy CpC4-. In another embodiment, r is 1, RB1 and RB2 are each independently -CH2-, and B is a substituted -C2-Ci-alkyl- group or is a -C2-Cp alkyl, -C2-C4 alkenyl-, -C2-alkynyl- group. C4-, -Ci-O alkyl-Cp alkyl or -CpNRa alkyl-unsubstituted Cp alkyl, said group being substituted -C2-C4 alkyl-, substituted with 1-2 substituents each independently selected from halogen, hydroxy, -O-P( O)(OH)2, -O-R(O)(R'Rn)2, amino, (alkyl CpCQamino-, (alkyl CpCjXalkyl CpCOamino-, halo(alkyl CpC4), halo(alkoxyCpC,)-, and alkoxy CpCp . In selected embodiments, r is 1, RB1 and RB2 are each independently -CH2-, and B is -CH=CH-, -CH2CH2-, -CH(OH)CH(OH)-, or -CH2N(CH3)CH2-. In these embodiments, r is 1, B, taken together with RB1 and RB2, forms a group -CH2CH=CHCH2-, -CH2CH2CH2CH2-, CH2CH(OH)CH(OH)CH2- or -CH2CH2N(CH3)CH2CH2-. IF-2019-16742483-APN-ANP#INPI 54 Page 54 of 402 - In these embodiments, r is 1, B, taken together with RB1 and RB2, forms a -CH2CH=CHCH2-. In one embodiment of the compounds of the present invention, s is 1 and RC1 and RC2 are each independently -CH2-, and C, taken together with RC1 and RC2, forms a linking group, where C is -halo(CrCi2 alkyl)-, -CrCi2-alkyl- optionally substituted, C2-Ci2-alkenyl- optionally substituted, C2-Ci2-alkynyl- optionally substituted, -Ci-Cg-O-alkyl-Ci-C6-alkyl- optionally substituted, -CrC6-alkyl-NRa-Ci-C6-alkyl- optionally substituted, -Ci-Cg alkyl-(C3-C6 cycloalkyl)-Ci-C6 alkyl- optionally substituted, -Ci-C6 alkyl-phenyl-Ci-Cg alkyl- optionally substituted, -Ci-C6 alkyl-(heterocycloalkyl 4-6-membered)-optionally substituted Ci-C6-alkyl, or -optionally substituted -Ci-C6-alkyl-(5-6-membered heteroaryl)-Ci-C6-alkyl, wherein the alkyl moiety of said -Ci-alkyl- Ci2- optionally substituted, C2-Ci2-alkenyl optionally substituted, C2-Ci2-alkynyl- optionally substituted, -Cj-Cg-O-alkyl-Ci-C6-alkyl- optionally substituted, -Ci-C6-alkyl-NRa-CrCg-alkyl- optionally substituted , -Ci-Cg alkyl-(C3-C6 cycloalkyl)-optionally substituted Ci-Cg alkyl, -CrCg alkyl-phenyl-optionally substituted Ci-C6 alkyl, -Ci-C6 alkyl-(4-6 membered heterocycloalkyl) -I rent Cj-Cg- optionally substituted, or -alkyl Ci-Cg-(5-6 membered heteroaryl)-optionally substituted Ci-Cg-alkyl is optionally substituted with 1 or 2 substituents each independently selected from halogen, halo(C1 alkyl- C4), -OH, -ORC, -NH2, -NRcRd, -OCORC, -CO2H, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc, and the C3-C6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said -Ci-Cg alkyl-(C3-Cg cycloalkyl)-Cj-Cg alkyl- optionally substituted, -Ci alkyl- Cg-phenyl-alkyl CpCg- optionally substituted, -alkyl CrCg-(4-6-membered heterocycloalkyl)-alkyl CrCg- optionally substituted, or -alkyl CrCg-(5-6-membered heteroaryl)-alkyl Cj-Cg- optionally substituted is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, amino, (CrCOamino alkyl, (Ci-C4 alkyl)(Ci-C^alkyl, C1-C4 alkyl, halo(C1-C4 alkyl ), halo(C1-C4 alkoxy)-, C1-C4 alkoxy-, hydroxy-(C2-C4 alkoxy)-, and Ci-C4 alkoxy-(C1-C4 alkoxy)-. In one embodiment of the compounds of the present invention, s is 1 and R and R are each independently -CH2-, and C, taken together with RC1 and Rc2, forms a IF-2019-16742483-APN-ANP#INPI55 Page 55 of 402 linker group, where C is -halo(CrCi2 alkyl)-, -optionally substituted Ci-Ci2 alkyl, optionally substituted C2-Ci2 alkenyl, optionally substituted C2-Ci2 alkynyl, -Cj-CgO alkyl- CrC6-alkyl- optionally substituted, -CrCg-NRa-alkyl-Cj-Cg-alkyl- optionally substituted, -Ci-C6-alkyl-(C3-C6 cycloalkyl)-Ci-C6-alkyl- optionally substituted, -Cj-Cg-alkyl-phenyl-alkyl Ci-Cg- optionally substituted, -Ci-Cg-alkyl-(4-6-membered heterocycloalkyl)-optionally substituted Cj-Cg-alkyl, or -Ci-C6-alkyl-(5-6-membered heteroaryl)-Ci-alkyl -C6- optionally substituted, wherein the alkyl moiety of said -Ci-Ci2-alkyl- optionally substituted, C2-Ci2-alkenyl optionally substituted, C2-Ci2-alkynyl- optionally substituted, -Ct-Cg-O-alkyl-CpCg-alkyl- optionally substituted, -CrC6-NRa alkyl-Ci-Cg alkyl- optionally substituted, -Ci-Cg alkyl-(C3-Cg cycloalkyl)-Ci-Cg alkyl- optionally substituted, -Ci-Cg alkyl-phenyl-Ci-C6 alkyl- optionally substituted, -Ci-Cg-alkyl-(4-6-membered heterocycloalkyl)-alkyl Cj-Cg- optionally substituted, or -alkyl Ci-Cg-(5-6 membered heteroaryl)-optionally substituted Ci-Cg-alkyl is optionally substituted with 1 or 2 substituents each independently selected from halogen, halo(Cj-alkyl G»), -OH, -O-P(O)(OH)2, -Ο-Ρ(Ο)(^π)2, -ORC, -NH2, -NRcRd, -OCORc, -CO2H, -CO2Rc, -SORC, -SO2RC, -CONH2, -CONRcRd, -SO2N H2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, - NRdCO2Rc, and -NRdSO2Rc, and the C3-C6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said -Ci-C6 alkyl-(C3-Cg cycloalkyl)-CpCg alkyl- optionally substituted, -Ci-Cg alkyl- optionally substituted phenyl-Ci-Cg-alkyl, -optionally substituted -Ci-Cg-alkyl-(4-6-membered heterocycloalkyl)-optionally substituted-Ci-C6-alkyl, or -CrCg-alkyl-(5-6-membered heteroaryl)-Q-alkyl- Optionally substituted Cg- is optionally substituted by 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -O-PIOXR'rHX, amino, (alkyl Ci-COamino-, (alkyl Ci -C4)(Ci-Gjamino-alkyl, C1-C4 alkyl, halo(C1-C4 alkyl), halo(C1-C4 alkoxy)-, C1-C4 alkoxy-, hydroxy-(CrCl alkoxy)-, C2-C4 alkoxy)-O-P(O)(OH)2, -(CrGXO-PtOXR'R11 alkoxy)^ and Ci-C4 alkoxy-(CrC4 alkoxy)-. In one embodiment of the compounds of the present invention, s is 1, RC1 and RC2 are each independently -CH2-, and C, taken together with RC1 and RC2, forms a 4-8 member linker group. In a further embodiment, s is 1 and C, taken together with RC1 and RC2, forms a 4-6 member linker group. In another embodiment IF-2019-16742483-APN-ANP#INPI 56 Page 56 of 402 additionally, s is 1 and C, taken together with RC1 and RC2, forms a 5-member linking group. In another embodiment, s is 1, RC1 and RC2 are each independently -CH2-, and C is a substituted -C2-Ci0-alkyl- group or is a -C2-Cio-alkyl-, -C2-Ci0-alkenyl-, -C2-alkynyl group. -Cw-, -alkyl G-G-O-alkyl GO or -alkyl G-G-NRa-alkyl G-G- unsubstituted, said group being substituted -C2-Ci0-alkyl, substituted with 1-4 substituents each independently selected from halogen, hydroxy, amino , (G-G alkyl)amino-, (G'G alkyl)(Ci-C alkyl)amino-, halo(G_G alkyl), halo(C1-C4 alkoxy)-, and C1-C4 alkoxy-. In another embodiment, s is 1, RC1 and RC2 are each independently -CH2-, and C is a substituted -C2-Ci0-alkyl- group or is a -C2-Ci0-alkyl-, -C2-Ci0-alkenyl-, -C2-alkynyl group. -Cio-, -Ci-C4 alkyl-O-Cj-Gr alkyl or -CrG alkyl,-NRa-G-G alkyl- unsubstituted, said group being -C2-Ci0 alkyl- substituted, substituted with 1-4 selected substituents each independently between halogen, hydroxy, -O-P(O)(OH)2, -Ο-Ρ(Ο)(^π)2, amino, (Ci-G alkyl)amino-, (G-G alkyl)(G-G alkyl)amino- , halo(G-G alkyl), halo(G-G alkoxy)-, and G-G alkoxyIn another embodiment, s is 1, RC1 and RC2 are each independently -CH2-, and C is a substituted -C2-C8 alkyl- group or is a -G-C8 alkyl-, -C2-C8 alkenyl-, -C2-C8 alkynyl-, -G-G-O-alkyl-G-C2-alkyl- or -G-G-NRa-alkyl-G-G-alkyl- group being unsubstituted, said group being -C2-alkyl- -C8- substituted, substituted with 1-2 substituents each independently selected from halogen, hydroxy, amino, (G-G alkyl)amino-, (GG alkyl)(G-G alkyl)amino-, halo(G-G alkyl), halo(alkoxy) G-G)-, and alkoxy G-GIn another embodiment, s is 1, RC1 and RC2 are each independently -CH2-, and C is a substituted -C2-C8-alkyl- group or is a -G-C8-alkyl-, -alkenyl group G-C8-, -alkyl G-C8-, -alkyl G-G-O-alkyl G-C2- or -alkyl G-G'NRa-alkyl G-G- unsubstituted, said group being -alkyl G-C8- substituted, substituted with 1 -2 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -O-P(O)(R1Rii)2, amino, (alkyl G-G)amino-, (alkyl G-G)(alkyl G-G)amino -, halo(G-G alkyl), halo(G-G alkoxy)-, and G-G alkoxy. In another embodiment, s is 1, RC1 and RC2 are each independently -CH2-, and C is a substituted -G-G alkyl- group or is a group -G-G-alkyl-, -G-G-alkenyl-, -G-G-alkynyl-, -G-G-O-alkyl-G-C2-alkyl- or -G-G-NRa-alkyl-G-G-alkyl- unsubstituted, said group -G-C6-alkyl- being substituted, substituted with 1-2 substituents each independently selected from halogen, hydroxy, amino, (GG-alkyl)amino-, (GG-alkyl)(GG-alkyl)amino-, halo(GG-alkyl), halo(GG-alkoxy)-, and alkoxy G-GIn another embodiment, s is 1, RC1 and RC2 are each independently -CH2-, and C is a substituted -C2-C6-alkyl- group or is a -G-G alkyl-, -G-Ce-alkenyl-, -G-alkynyl group -EC-, IF-2019-16742483-APN-ANP#INPI57 Page 57 of 402 -CrC2-alkyl-O-CrC2-alkyl- or -CrC2-alkyl-NRa-Ci-C2-alkyl- unsubstituted, said group being -C2-C6-alkyl- substituted, substituted with 1-2 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -O-PIOXRV1)^ amino, (Ci-C alkyl^amino-, (Ci-C4 alkyl)(Ci-C4 alkyl)amino-, halo(C1-C0 alkyl, halo (Ci-C4 alkoxy)-, and Ci-Cp alkoxy. In another embodiment, s is 1, RC1 and RC2 are each independently -CH2-, and C is a -Q-Gr alkyl, -C2-C4 alkenyl- or -C2-C4 alkynyl- group. In selected embodiments, s is 1, RC1 and RC2 are each independently -CH2-, and C is -CH2CH2CH2-, where C, taken together with RC1 and RC2, forms a group -CH2CH2CH2CH2CH2-. In one embodiment of the compounds of the present invention, R4 and R6 are each independently selected from H, halogen, halo(Cy-Q alkyl), halo(CrCe alkoxy)-, hydroxy, -NH2, -NRcRc, -NRcRd, - CORc, -CO2Rc, -N(Rd)CORc, -N(Rd)SO2Rc, -N(R9)SO2(CrC2 alkyl)-N(Rh)(Rf), -N(R9)CO(CrC2 alkyl)-N (Rh)(Rf), optionally substituted (CrC6 alkyl), optionally substituted (Ci-C6 alkyl)ox¡-, (optionally substituted Cr^amino alkyl), and (Ci-C6 alkyl)(Ci-C^amino alkyl). optionally substituted, wherein (Ci-Ce alkyl) of said (Ci-C6 alkyl) optionally substituted, (Ci-C6 alkyl)ox¡- optionally substituted, (CrCejamino alkyl- optionally substituted and (Ci-C6 alkyl)(alkyl Optionally substituted Ci-COamino- is optionally substituted with 1-4 substituents each independently selected from -OH, -ORC, -NH2, -NRCRC, -NRcRd, -CO2H, -CO2Rc, -OCORc, -CO2H, -CO2Rc, - SORC, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, -NRdSO2Rc, optionally substituted phenyl, optionally substituted 5-6 membered heterocycloalkyl and a group optionally substituted 5-6 membered heteroaryl, wherein said optionally substituted phenyl, 5-6 membered heterocycloalkyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxy, amino, (alkyl Ci-C^amino-, (CrQXalkylCi-C4alkyl)amino-, Q-q alkyl, halo(C1-C4 alkyl), hydroxy-(Cj-C» alkyl)-, halo(CpC alkoxy)-, Ci alkoxy -Cr, hydroxy-(C2-C4 alkoxy)-, Ci-Cryalkoxy Cx-C4 alkoxy)-, -CORd, -CON(Rd)(Rf), and -CO2Rd. In one embodiment of the compounds of the present invention, R4 and R6 are each independently selected from H, halogen, halo(Ci-Q alkyl), halo(Ci-Cg alkoxy)-, hydroxy, -O-P(O)(OH)2 , IF-2019-16742483-APN-ANP#INPI 58 Page 58 of 402 -O-P(O)(RiRii)2, -NH2, -NRcRc, -NRcRd, -CORc, -CO2Rc, -N(Rd)CORc, -N(Rd)SO2Rc, -N(R9)SO2(alkyl CrC2)- N(Rh)(Rf), -N(R9)CO(CrC2 alkyl)-N(Rh)(Rf), (Cj-Q alkyl) optionally substituted, (Ci-C6 alkyl)ox¡- optionally substituted, (alkyl CrC6)amino- optionally substituted, and (Cj-CeX alkylCi-C^alkyl optionally substituted, wherein the (Q-Ce alkyl) of said optionally substituted (Ci-C6 alkyl), (Ci-Ce alkyl)oxy- optionally substituted, (optionally substituted Ci-Cgjamino alkyl and optionally substituted (Ci-C6 alkyl)(Ci-C4 alkyl)amino- is optionally substituted with 1-4 substituents each independently selected from -OH, -O-P(O)( OH)2, -Ο-Ρ(Ο)(^Π)2, -ORC, -NH2, -NRCRC, -NRcRd, -CO2H, -CO2Rc, -OCORc, -CO2H, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc , -NRdSO 2Rc, optionally substituted phenyl, optionally substituted 5-6-membered heterocycloalkyl and an optionally substituted 5-6-membered heteroaryl group, wherein said optionally substituted phenyl, 5-6-membered heterocycloalkyl or 5-6-membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxy, amino, (examino-alkyl, (Q-Qialkyl Ci-Cjjamino-alkyl, Ci-C4 alkyl, halo(Ci-C4 alkyl), hydroxy-(Ci-C4 alkyl) C1-C4)-, -(alkyl σι-0})-0-Ρ(0)(ΟΗ)2, -(alkoxy Ci-C4)-O-P(O)(RiRii)2, halo(alkoxy Cj-C» )-, C1-C4 alkoxy-, hydroxy-(alkoxy C2-C4)-, -(C2-C4 alkoxy)-O-P(O)(OH)2, -(CrGO-O-PtOXR'R11 alkoxy)?, Ci-C4 alkoxy-(CrQ-alkoxy, -CORd, -CON(Rd)( Rf), and -CO2Rd. In one embodiment, R4 and R6 are each H. In one embodiment of the compounds of the present invention, R14 is optionally substituted C1-C4 alkyl, wherein said optionally substituted Ci-CL alkyl is optionally substituted with a substituent selected from -ORC, -NRcRd, -CO2Rc, -CONRcRd, -SO2NRcRd , and -OCONRcRd. In one embodiment of the compounds of the present invention, R16 is H, halogen, or CrQ alkyl. In one embodiment of the compounds of the present invention, R15 and R17 are each independently H, cyclopropyl, or Ci-Q alkyl. In one embodiment of the compounds of the present invention, R14, R15, R16, and R17 are each independently H or Ci-C alkyl. In one embodiment of the present invention, R16 is H. IF-2019-16742483-APN-ANP#INPI59 Page 59 of 402 In another embodiment, R14, R15, and R17 are each independently C1-C4 alkyl. In another embodiment, R14, R15, and R17 are each independently C1-C3 alkyl, specifically, methyl or ethyl. In a selected embodiment, R14 is ethyl. In another embodiment, R15 and R17 are each methyl. In one embodiment of the compounds of the present invention, Raes H, Rc, -CORc, -CO2H, -CO2Rc, -SORC, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, or -SO2NRcRd. In another embodiment, Raes H, C1-C4 alkyl, -CO(C1-C4 alkyl), -CO(Ci-C^-alkyl, -CO(Ci-q alkyl)-O-(Crq alkyl), -CO(Crq alkyl)-NH2, -CO(Ci-q alkyl)-NH(C1-C4 alkyl), or -CO(Crq alkyl)- N(CpCO alkyl(C1-C4 alkyl). An embodiment of the present invention relates to a compound of formula (I-N), of formula (I) or of formula (I-P), wherein: q + r + s = 1 or 2; q is 0 and RA1 and RA2 are independently selected from H, -OCH2CH2CH2OH and OCH3; or q is 1, RA1 and RA2 are each -O-, and A is -CH2CH2CH2-; r is 0 and RB1 and RB2 are each H; or r is 1, RB1 and RB2 are each independently -CH2-, and B is -CH=CH-, -CH2CH2-, -CH(OH)CH(OH)-, or -CH2N(CH3)CH2-; s is 0, RC1 is methyl and RC2 is ethyl; or s is 1, RC1 and RC2 are each independently -CH2-, and C is -CH2CH2CH2-; R3 and R5 are each -CONH2; R4 and R6 are each H; R14 is ethyl; R15 is methyl; R16 is H; R17 is methyl; or a salt, in particular a pharmaceutically acceptable salt thereof. In one embodiment of the present invention, the compound of the invention has the formula (I-NIF-2019-16742483-APN-ANP#INPI θθ Page 60 of 402 where R3 and R5 are each independently -CON(Rd)(Rf), or one of R3 and R5 is -CON(Rd)(Rf), and the other of R3 and R5 is H, COOH or -CO2(Rc); Rces Ci-C4 alkyl; rbi and rbz are cac|a independently -CH2-; B is -halo(C4-C5 alkyl), -unsubstituted C4-C5 alkyl, or -unsubstituted C2-Cs* alkenyl; ra2 and ra1 are each independently H, halogen, hydroxyl, -O-P(O)(OH)2, -OPÍOXR'R11)^ (optionally substituted Ci-C6 alkyl), or (optionally substituted (CrC6 alkyl)ox¡-, wherein Ci-Q alkyl of said optionally substituted (CrC6 alkyl), or optionally substituted (Ci-C6 alkyl)ox¡- is optionally substituted with 1-4 substituents each independently selected from the group consisting of hydroxyl, -O-P(O) (OH)2, -O-PIOXR'R11)^ C1-C4 alkoxy, -N(Re)(Rf), -CO2(Rf), optionally substituted phenyl, and optionally substituted 5-6 membered heterocycloalkyl; wherein said optionally substituted phenyl, or 5-6 membered heterocycloalkyl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -Ο-ΡίΟχρνχ, amino, (Cj alkyl-Cejamino-, (CrC6 alkyl)(CrC6 alkyl)amino-, halo(Ci-Cg alkyl), hydroxy-(C1-C4 alkyl)-, -(CrC4 alkyl)-O-P (O)(OH)2, -(Cj-GO-O-PIOX^rHX alkoxy, halo(C1-C4 alkoxy)-, C1-C4 alkoxy-, hydroxy-(C2-C4 alkoxy)-, -( alkoxy C2-C4)-O-P(O)(OH)2, IF-2019-16742483-APN-ANP#INPI61 Page 61 of 402 -(alkoxy Cz-CO-O-PtOXR'R11^, -(alkyl Ci-C6)-NH2, -alkyl CrC4-(alkoxy CrQ) and alkoxy CpC^alkoxy C1-C4)-; each Rdes independently H or CrC4 alkyl; Rese selected from H, (C1-C4 alkyl), -CO (C1-C4 alkyl), -OCO (C1-C4 alkyl), -(C1-C4 alkyl C1-C4)-NH2, -(C1-C4 alkyl)C1-C4 alkoxy, or -CO2(C1-C4 alkyl), each occurrence of Rfes H or (C1-C4 alkyl); R4 and R6 are H; R14 is CrC4 alkyl; RC1 is H or C1-C4 alkyl; RC2is Ci-C4 alkyl; R15is H or C1.C4 alkyl; R16is H or C1-C4 alkyl; R17is H or C1-C4 alkyl; and each occurrence of R1 and Rnes independently (Ci-C6 alkyl)oxy-, or a tautomer thereof, or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment of the present invention, the compound of the invention has the formula (I-PB') where R3 and R5 are each independently -WITH(Rd)(Rf), or one of R3 and R5 IF-2019-16742483-APN-ANP#INPI 62 Page 62 of 402 is -CON(Rd)(Rf), and the other of R3and R5is H, COOH or -CO2(Rc); Rces alkyl Cj-C4; rbi and rb2 are box one independently -CH2-; B is -halo(C1-C5 alkyl), -unsubstituted C1-C5 alkyl, or -unsubstituted C2-Cs-alkenyl; ra2 and RA1 are each independently H, halogen, hydroxyl, -O-P(O)(OH)2, -0Ρ(Ο)^^Π)2, (CrC6 alkyl) optionally substituted, or (CrC6 alkyl)ox¡- optionally substituted, wherein the Ci-C6 alkyl of said optionally substituted (Ci-C6 alkyl), or optionally substituted (Ci-C6 alkyl)ox¡- is optionally substituted with 1-4 substituents each independently selected from the group consisting of hydroxyl, - O-P(O)(OH)2, -O-P(O)(RiRii)2, C1-C4 alkoxy, -N(Re)(Rf), -CO2(Rf), optionally substituted phenyl, and optionally substituted 5-6 membered heterocycloalkyl; wherein said optionally substituted phenyl, or 5-6 membered heterocycloalkyl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -Ο-ΡίΟχΡ^Ηχ, amino, (CrCeJamino alkyl-, (Cj-CeX alkyl Ci-C6 alkyl)amino-, halo(Ci-C6 alkyl), hydroxy-(C1-C4 alkyl)-, -(Ci-C4 alkyl) )-O-P(O)(OH)2, -(C1-C4 alkoxy)-O-P(O)(RiRii)2, halo(C1-C4 alkoxy)-, C1-C4 alkoxy-, hydroxy-(C2 alkoxy- C4)-, -(alkoxy CrGQ-O-PIOXOHX, -(alkoxy CrCO-O-PIOXR’R11);!, -(alkyl Ci-C6)-NH2, and alkoxy Ci-CHalkoxy CpG)-; each Rdes independently H or alkyl CrG; Rese selected from H, (Ci-Q alkyl), -CO (Ci-C4 alkyl), -OCO (CrG alkyl), -(Ci-C4 alkyl), Ci-CO-NH,, -(Ci-C4 alkyl) alkoxy CrG, or -CO2(CrC4 alkyl), each occurrence of Rfes H or (CrCO alkyl; R4 and R6 are H; R14is alkyl CrG; RC1is H or Ci-C alkyl»; RC2is CrC4 alkyl; R15is H or Ci-C4 alkyl; R16is H or Ci-G alkyl; R17is H or Cj-G alkyl; and each occurrence of R1 and Rnes independently (Ci-Ce alkyl)oxy-, or a tautomer thereof, or a salt thereof, in particular a pharmaceutically acceptable salt thereof. IF-2019-16742483-APN-ANP#INPI63 Page 63 of 402 In one embodiment of the present invention, the compound of the invention is of formula (I-B') where R3and R5are each independently -CON(Rd)(Rf), or one of R3and R5is -CON(Rd)(Rf), and the other of R3and R5is H or -CO2(Rc); Rces alkyl CrQ; RB1 and Rb2 are each independently -CH2-; B is -halo(Ci-C5 alkyl), -unsubstituted Ci-C5 alkyl, or -unsubstituted C2-C5 alkenyl; Ra2 and RA1 are each independently H, halogen, hydroxyl, (CrCg alkyl) optionally substituted, or (CrCg alkyl)oxy-, wherein the CrCg alkyl of said optionally substituted (CrCg alkyl), or (CrCg alkyl)oxy- optionally substituted is optionally substituted with 1-4 substituents each independently selected from the group consisting of hydroxyl, C1-C4 alkoxy, -N(Re)(Rf), -CO2(Rf), optionally substituted phenyl, and heterocycloalkyl -6 members optionally replaced; wherein said optionally substituted phenyl, or 5-6 membered heterocycloalkyl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -O-PIOXR'R11);" , amino, (CrCg alkyl)amino-, (CrCg alkyl)(CrCg alkyl)amino-, halo(CrCg alkyl), hydroxy-(CrQ alkyl)-, halo(C1-C4 alkoxy)-, C1-C4 alkoxy-, hydroxy-(alkoxyQrC,)-, and alkoxyCrCr(alkoxyCrQ)-; each Rdes independently H or C1-C4 alkyl; IF-2019-16742483-APN-ANP#INPI64 Page 64 of 402 Rese selected from H, (Ci-Cj alkyl), -CO (C1-C4 alkyl), -OCO (C1-C4 alkyl), or -CO2 (C1-C4 alkyl); each Rfes H or (CrC4 alkyl); R4 and R6 are H; R14 is C1-C4 alkyl; RC1 is H or C1-C4 alkyl; RC2 is C1-C4 alkyl; R15is H or C1.C4 alkyl; R16is H or C1-C4 alkyl; R17is H or C1.C4 alkyl; and each occurrence of R1 and R11 is independently (alkyl CrC6)ox¡-, a tautomer, a salt, or a prodrug thereof. In one embodiment of the present invention, the compound of the invention is of formula (I-N- Formula (I-N-b') where B is -halo(C4-C5 alkyl), -unsubstituted C1-C5 alkyl, or -unsubstituted C2-Cs-alkenyl; ra2 and ra1 are each independently H, halogen, hydroxyl, -O-P(O)(OH)2, -Ο-Ρ(Ο)(^Π)2, optionally substituted (Ci-C6 alkyl), or (Ci-C6 alkyl) oxy-optionally substituted, wherein the Ci-Ce alkyl of said optionally substituted (Cj-Ce alkyl) or (optionally substituted (Ci-C6 alkyl)oxy- is optionally substituted with 1-4 IF-2019-16742483-APN-ANP#INPI65 Page 65 of 402 substituents each independently selected from the group consisting of hydroxyl, C1-C4 alkoxy, -N(Re)(Rf), -CO2(Rf), optionally substituted phenyl, and optionally substituted 5-6 membered heterocycloalkyl, and wherein said optionally substituted phenyl, or 5-6 membered heterocycloalkyl is optionally substituted with 1- 4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -Ο-Ρ(Ο)^^Π)2, amino, (alkyl Ci-Cgjamino-, (alkyl CrC6)(alkyl Ci -Cgjamino-, halo(CrC6 alkyl), hydroxy-(C1-C4 alkyl)-, -(Ci-C4 alkyl)-O-P(O)(OH)2, -(CrC4 alkoxy)-O-P(O)(RiRn) 2, halo(C1-C4 alkoxy)-, C1-C4 alkoxy-, hydroxy-(C2-C4 alkoxy)-, -(C2-C4 alkoxy)-O-P(O)(OH)2, -(Cz-C^j-O-PCOjíR'R11 alkoxy)^ -(Ci-C6 alkyl)-NH2, -CrC4 alkyl-(C1 alkoxy- C4) and Ci-C4 alkoxy-(C1-C4 alkoxy)-; Reselected from H, (C1-C4 alkyl), -CO (C1-C4 alkyl), -OCO (C1-C4 alkyl), -(Ci-C4 alkyl)-NH2, -(C1-C4 alkyl) Cj-Cj alkoxy, or -CO2(C1-C4 alkyl), each Rfes H or (C1-C4 alkyl); R14is Ci-C4 alkyl; RC2is Ci-C4 alkyl; R15 is C1-C4 alkyl; and R17is Ci-C4 alkyl; each occurrence of R1 and Rnes independently (Ci-C6 alkyl)ox¡-, a tautomer, a salt, or a prodrug thereof. In one embodiment of the present invention, the compound of the invention has the formula (I-PbD, IF-2019-16742483-APN-ANP#INPI66 Page 66 of 402 EITHER EITHER R15 where B is -halo(CrC5 alkyl), -unsubstituted Cj-Q alkyl, or -unsubstituted C2-C5-alkenyl; ra2 and ra1 are each independently H, halogen, hydroxyl, -O-P(O)(OH)2, -OΡ(Ο)(ΐνκπ)2, optionally substituted (Ci-C6 alkyl), or (Ci-C6 alkyl)ox¡- optionally substituted, wherein the Ci-C6 alkyl of said optionally substituted (Ci-C6 alkyl), or optionally substituted (Ci-C6 alkyl)ox¡- is optionally substituted with 1-4 substituents each independently selected from the group consisting of hydroxyl, C1-C4 alkoxy, -N(Re)(Rf), -CO2(Rf), optionally substituted phenyl, and optionally substituted 5-6 membered heterocycloalkyl, and wherein said optionally substituted phenyl, or 5-6 membered heterocycloalkyl is optionally substituted with 1- 4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -O-PIOXR'R11^, amino, (alkyl CrCgjamino-, (alkyl Ci-CeXalkyl Ci-Cejamino-, halo(alkyl Ci -Cg), hydroxy-(CrQ alkyl)-, -(Ci-C4 alkyl)-O-P(O)(OH)2, -(CrC4 alkoxy)-O-P(O)(RiRn)2, halo(C1 alkoxy- C4)-, C1-C4 alkoxy-, hydroxy-(C2-C4 alkoxy)-, -(C2-C4 alkoxy)-O-P(O)(OH)2, -(C2-C4 alkoxy)-O-P(O)(RIRII)2, -(Ci-C^-NH^ alkyl and Ci-C4 alkoxy- (alcox¡ Cj-Q)-; Reselected from H, (CrQ alkyl), -CO (CrG alkyl), -OCO (CrG alkyl), IF-2019-16742483-APN-ANP#INPI67 Page 67 of 402 -(CrC4 alkyl)-NH2, -(C1-C4 alkyl) C1-C4 alkoxy, or -CO2(C1-C4 alkyl), each Rfes H or (C1-C4 alkyl); R14 RC2 R15 R17is alkyl CrQ; is C1-C4 alkyl; is C1.C4 alkyl; and is C1.C4 alkyl; each occurrence of R1 and Rnes independently (Ci-C6 alkyl)ox¡-, a tautomer, a salt, or a prodrug thereof. In one embodiment of the present invention, the compound of the invention has the formula (Ib'), b where B is -halo(CpCs alkyl), -unsubstituted CrC5 alkyl, or -unsubstituted C2-C5 alkenyl; Ra2 and RA1 are each independently H, halogen, optionally substituted (Ci-C6 alkyl), or optionally substituted (Ci-C6 alkyl), or optionally substituted (Ci-C6 alkyl), or optionally substituted (C!-C6 alkyl)oxy- is optionally substituted with 1-4 substituents each independently selected from the group consisting of hydroxyl, C1-C4 alkoxy, -N(Re)(Rf), -CO2(Rf) , optionally substituted phenyl, and optionally substituted 5-6 membered heterocycloalkyl, and wherein said optionally substituted phenyl, or 5-6 membered heterocycloalkyl is optionally substituted IF-2019-16742483-APN-ANP#INPI 68 Page 68 of 402 with 1-4 substituents each independently selected from halogen, hydroxy, amino, (CrC6 alkyl)amino-, (Ci-C6 alkyl)(CrC6 alkyl)amino-, halo(C»-Cg alkyl), hydroxy -(CrC» alkyl)-, halo(CrC» alkoxy)-, CrC» alkoxy-, hydroxy-(C2-C4 alkoxy)-, and Cj-C4 alkoxy-(CrC» alkoxy)-; Rees H, (CpQ alkyl), -CO(CrC alkyl), -OCO(CrC4 alkyl), or -CO2(Cj-C alkyl), each occurrence of Rfes H or (Ci-C4 alkyl); R14is alkyl CrC»; RC2is alkyl CrC»; R15is Ci.C4 alkyl; and R17is Ci-C alkyl»; each occurrence of R1 and Rnes independently (Ci-C6 alkyl)ox¡-, a tautomer, a salt, or a prodrug thereof. In one embodiment, the compound of formula (I-N-B'), (I-P-B'), (I-N-b'), or (I-P-b'), where RA2 and RA1 are each independently H, halogen, (alkyl Cj-Cg) optionally substituted, or optionally substituted (Ci-Cg alkyl)oxy-, and the Cj-Cg alkyl of said optionally substituted (Cr Cg alkyl), optionally substituted (Ci-Cg alkyl)oxy- is optionally substituted with 1-4 substituents each independently selected from the group consisting of hydroxyl, -O-P(O)(OH)2, -O-PIOjíR'R1^, -N(Re)(Rf), alkoxy CrC", phenyl, heterocycloalkyl 5-6 membered optionally substituted ring containing at least one nitrogen or oxygen as a ring member, each Rese independently selected from H, (Cj-C» alkyl), -(Ci-C» alkyl)-NH2, or -(Cj-C» alkyl)-NH2, or -(Cj-C» alkyl) Cj-C»)alkoxy Cj-C» and each Rfes independently H or (alkyl CrC»). In one embodiment, the compound of formula (I-N-B^, (I-P-B'), (I-B'), (I-N-b'), (I-P-b') or (I-b'), where RA2y RA1 are each independently H, halogen, (Q-Cg alkyl) optionally substituted, or (Ci-Cg alkyl)ox¡-, and the C»-Cg alkyl of said optionally substituted (C»-Cg alkyl), ( optionally substituted CrCg)oxy alkyl is optionally substituted with 1-4 substituents each independently selected from the group consisting of hydroxyl, -N(Re)(Rf), CrC alkoxy", phenyl, optionally substituted 56-membered heterocycloalkyl contains at least one nitrogen or oxygen as a ring member, and Rey Rf are each independently H o (CrC4 alkyl). In one embodiment, the compound of formula (I-N-B^, (I-P-B'), (I-N-b'), or (I-P-b'), wherein at least one of RA2 or RA1 is independently H, halogen, (CrC alkyl >) optionally substituted, or (alkyl CrCg)oxy- optionally substituted, and the C»-Cg alkyl of IF-2019-16742483-APN-ANP#INPI69 Page 69 of 402 said optionally substituted (Q-G alkyl), optionally substituted (Ci-C6 alkyl)ox¡- is optionally substituted with 1-4 substituents independently selected from N(Re)(Rf), tetrahydropyran, pyrrolidinyl, piperazinyl, piperidyl and morpholinyl, each Rese independently selected from H, (G-G alkyl), -(G-G alkyl)-NH2, or -(Ci-C4 alkyl)G-G alkoxy and each Rfes independently H or (G’G alkyl)· In one embodiment, the compound of formula (I-N-B'), (I-P-B'), (I-B'), (I-N-b'), (I-P-b') or (I-b'), wherein at least one of RA2 or RA1 is each independently H, halogen, (Ci-C6 alkyl) optionally substituted, or (G-G alkyl)ox¡-, and the Ci-C6 alkyl of said (Ci-C6 alkyl) optionally substituted , optionally substituted (alkyl G-G)ox¡- is optionally substituted with 1-4 substituents independently selected from -N(Re)(Rf), tetrahydropyran, pyrrolidinyl, piperazinyl, piperidyl or morpholinyl, and Rey Rf are each independently H or (alkyl G_G)· In one embodiment, the compound of formula (I-N-B'), (I-P-B'), (I-B'), (I-N-b'), (I-P-b') or (I-b'), where B is -unsubstituted Ci-C5 alkyl, or -unsubstituted -C2-C5-alkenyl; ra2 and ra1 are each independently H, halogen, (G_G alkyl) optionally substituted, or (G-G alkyl)ox¡- optionally substituted, wherein the Ci-C6 alkyl of said (Ci-C6 alkyl) optionally substituted, or (Ci-C6 alkyl )oxy-optionally substituted is optionally substituted with 1-2 substituents each independently selected from the group consisting of hydroxyl, G-G alkoxy, -N(Re)(Rf), -CO2(Rf), unsubstituted phenyl and unsubstituted 5-6 membered heterocycloalkyl, Rees H, (CrG alkyl), -CO(CrG alkyl), -OCO(G’G alkyl), or -CO2(G’G alkyl), each occurrence of Rfes H or (G-G alkyl); R14 is C1-C4 alkyl; RC2is alkyl CrG; R15 is C1-C4 alkyl; and R17is CpQ alkyl; each occurrence of R1 and Rnes independently (alkyl CrC6)oxy-, or a tautomer thereof, or a salt thereof, or a prodrug thereof. IF-2019-16742483-APN-ANP#INPI70 Page 70 of 402 In one embodiment, the compound of formula (I-b'), wherein B is unsubstituted -C2-C5-alkenyl; ra2 and ra1 are each independently H, (Ci-C6 alkyl) optionally substituted, or (CrC6 alkyl)oxy- optionally substituted, wherein the CrC6 alkyl of said (CrCg alkyl) optionally substituted, or (Ci-C6 alkyl)oxy- optionally substituted is optionally substituted with 4 substituents each independently selected from the group consisting of hydroxyl, C1-C4 alkoxy, unsubstituted 5-6 membered heterocycloalkyl, R14 is C1-C4 alkyl; RC2 is C1-C4 alkyl; R15 is C1-C4 alkyl; and R17is C1.C4 alkyl; or a tautomer thereof, or a salt thereof, or a prodrug thereof. In one embodiment, the compound of formula (I-b'), wherein B is unsubstituted ethenyl; rA2 and ra1 are each independently H or optionally substituted (Ci-C6 alkyl)oxy-, wherein the CrCg alkyl of said optionally substituted (CrCg alkyl)oxy- is optionally substituted with a substituent selected from hydroxyl or unsubstituted morpholinyl; R14 is methyl or ethyl; RC2is methyl or ethyl; R15 is methyl or ethyl; and R17 is methyl or ethyl; or a tautomer thereof, or a salt thereof, or a prodrug thereof. In one embodiment, the compound of formula A, IF-2019-16742483-APN-ANP#INPI71 Page 71 of 402 where P is an integer between 1 to 6, Ray RB is independently H, (C1-C4 alkyl) or N, Ray Rb forms an optionally substituted 5- or 6-membered heterocyclic ring, wherein the heterocyclic ring is selected from the group consisting of morpholinyl, piperidinyl, piperazinyl and pyrrolidinyl, and the heterocyclic ring is optionally substituted with one or two substituents independently selected from the group consisting of hydroxyl and Cj10 C3 alkyl optionally substituted with one or two hydroxyl or C1-C3 alkoxy substituents, or a tautomer thereof, or a salt thereof, or a prodrug thereof. In one embodiment, the compound of the invention has the formula (I-P-bc) IF-2019-16742483-APN-ANP#INPI72 Page 72 of 402 or where RC1 and RC2 are each independently -CH2-, C is -halo(Ci-C5 alkyl), -unsubstituted CrC5 alkyl, or -unsubstituted C2-C5 alkenyl; RB1 and Rb2 are each independently -CH2-; B is -halo(C1-C5 alkyl), -unsubstituted C1-C5 alkyl, or -unsubstituted C2-Cs-alkenyl; Ra2 and RA1 are each independently H, halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(RiRii)2, (Ci-C6 alkyl) optionally substituted, or (Cj-C6 alkyl)ox¡optionally substituted, wherein the Ci-C6 alkyl of said optionally substituted (Ci-C6 alkyl), or optionally substituted (Ci-C6 alkyl)ox¡- is optionally substituted with 1-4 substituents each independently selected from the group consisting of hydroxyl , -O-P(O)(OH)2, - Ο-Ρ(Ο)(^Π)2, Cj-q alkoxy, -N(Re)(Rf), -CO2(Rf), optionally substituted phenyl, and optionally substituted 5-6 membered heterocycloalkyl; wherein said optionally substituted phenyl, or 5-6 membered heterocycloalkyl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, - O-P(O)(R'Rn)2, amino, (Ci-C6 alkyl)amino-, (Ci-C6 alkyl)(Q-Cejamino alkyl-, halo(Ci-C6 alkyl), hydroxy-(C1 alkyl- C4)-, -(Ci-q alkyl)-O-P(O)(OH)2, -(Ci-q alkoxy)-O-P(O)(R!Rn)2, halo(alkoxy¡ Crq)-, C1 alkoxy -C4-, hydroxy-(C2-q alkoxy)-, -(C2-Q alkoxy)-O-P(O)(OH)2, - (C2-q alkoxy)-O-P(O)(RIRII)2, -(C!-C6 alkyl)-NH2, and Ci-C4 alkoxy-(Crq alkoxy)-; each Rdes independently H or q-Q alkyl; IF-2019-16742483-APN-ANP#INPI73 Page 73 of 402 Reselected from H, (CrC4 alkyl), -CO(CpCi alkyl), -OCO(CpC alkyl), -(CrC4 alkyl)-NH2, -(Ci-C4 alkyl) CrQ alkoxy, or -CO2(CpC alkyl), each Rfes H or (CrQ alkyl); R6is H; R14 is Cj-Q alkyl; R15is Ci-Q alkyl; R16is alkyl CiA; R17 is Ci-C4 alkyl; and each occurrence of R1 and Rnes independently (Ci-C6 alkyl)oxy-, or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment, the compound of the invention has the formula (I-bc) Where RC1 and Rc2 are each independently -CH2-, C is -halo(Ci-C5 alkyl), -unsubstituted Ci-C5 alkyl, or -unsubstituted C2-C5 alkenyl; rbi and rb2 are each independently -CH2-; B is -halo(Ci-C5 alkyl), -unsubstituted Ci-C5 alkyl, or -unsubstituted C2-C5 alkenyl; ra2 and ra1 are each independently H, halogen, hydroxyl, optionally substituted (Ci-C6 alkyl), or optionally substituted (CrC6 alkyl), or optionally substituted (Ci-C6 alkyl), wherein the Ci-Q» alkyl of said optionally substituted (Ci-C6 alkyl), or (optionally substituted alkylCrQOoxy- is optionally substituted with 1-4 IF-2019-16742483-APN-ANP#INPI74 Page 74 of 402 substituents each independently selected from the group consisting of hydroxyl, C1-C4 alkoxy, -N(Re)(Rf), -CO2(Rf), optionally substituted phenyl, and optionally substituted 5-6 membered heterocycloalkyl ; wherein said optionally substituted phenyl, or 5-6 membered heterocycloalkyl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxy, amino, (Ci-CeJamino-alkyl, (Ci-C6 alkyl)(Ci-alkyl) C6)amino-, halo(Ci-C6 alkyl), hydroxy-(C1-C4 alkyl)-, halo(C1-C4 alkoxy)-, C1-C4 alkoxy-, hydroxy-(C2-C4 alkoxy) and CrCryalkoxy Ci-C,)-; each Rdes independently H or CrC4 alkyl; Rese selected from H, (CrC4 alkyl), -CO (CpC» alkyl), -OCO (Ci-CO alkyl, or -CO2 (Ci-Cj alkyl), each Rfes H or (C1-C4 alkyl); R6is H; R14 is optionally substituted Ct-C4 alkyl; R1Ses alkyl CVC4; R16is alkyl Cj.C»; R17is Ci-Q alkyl; and each occurrence of R1 and Rnes independently (Ci-C6 alkyl)oxy-, or a tautomer thereof, or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment, the compound of formula (I-P-bc), wherein RA2 and RA1 are each independently H, halogen, optionally substituted (Ci-Cg alkyl), or optionally oxy-substituted (Ci-Cg alkyl), and the Ci-C6 alkyl of said optionally substituted (Ci-Q alkyl), optionally substituted (Ci-C6 alkyl)ox¡- is optionally substituted with 1-4 substituents each independently selected from the group consisting of hydroxyl, -0P(O)(OH) 2, -Ο-Ρ(Ο)^π)2, -N(Re)(Rf), Ci-C4 alkoxy, phenyl, optionally substituted 5-6 membered heterocycloalkyl containing at least one nitrogen or oxygen as ring member , each Rese independently selected from H, (Ci-C4 alkyl), -(Ci-C4 alkyl)-NH2, or -(Ci-C4 alkyl, Ci-C4 alkoxy) and each Rfes independently H or (Ci-C alkyl,). In one embodiment, the compound of formula (I-P-bc) or (I-bc), wherein RA2 and RA1 are each independently H, halogen, optionally substituted (CrC6 alkyl), or optionally substituted (CrCg alkyl)oxy, and the Cj-Ce alkyl of said optionally substituted (Cj-Ce alkyl), (optionally substituted CrCejoxy-alkyl is optionally substituted with 1-4 substituents each independently selected from the group consisting of hydroxyl, -N(Re)(Rf), Ci-C4 alkoxy, phenyl, 5-6 membered heterocycloalkyl optionally IF-2019-16742483-APN-ANP#INPI 75 Page 75 of 402 substituted containing at least one nitrogen or oxygen as a ring member, and Rey Rf are each independently H o (CrC4 alkyl). In one embodiment, the compound of formula (I-P-bc), wherein at least one of RA2 or RA1 is independently H, halogen, optionally substituted (CrC8 alkyl), or optionally substituted (CrC8 alkyl)ox¡-, and the Ci alkyl -Ce of said optionally substituted (CrC6 alkyl), (optionally substituted Cj-CeJoxy-alkyl is optionally substituted with 1-4 substituents independently selected from -N(Re)(Rf), tetrahydropyran, pyrrolidinyl, piperazinyl, piperidyl and morpholinyl, each Rese is independently selected from H, (Ci-Q alkyl), -(Ci-Cjj-NHz alkyl, or -(Ci-CO alkyl CpC, and each Rfes independently H or (Ci-Cí alkyl). In one embodiment, the compound of formula (I-P-bc) or (I-bc), wherein at least one of RA2 or Ra1 is each independently H, halogen, (Ci-C6 alkyl) optionally substituted, or (Ci-C6 alkyl )oxy- optionally substituted, and the Ci-C6 alkyl of said (Cr C6 alkyl) optionally substituted, (Ci-C6 alkyl)oxy- optionally substituted is optionally substituted with 1-4 substituents independently selected from -N(Re)(Rf ), tetrahydropyran, pyrrolidinyl, piperazinyl, piperidyl or morpholinyl, and King Rf are each independently H o (Ci-C4 alkyl). Representative compounds of the present invention include the example compounds. It will be appreciated that the present invention encompasses compounds of formula (I-N), of formula (I) and of formula (I-P) in the form of the free base and as salts thereof, for example, in the form of a pharmaceutically acceptable salt of the themselves. In one embodiment, the present invention relates to compounds of formula (I-N), of formula (I) and of formula (IP) in the form of a free base. In another embodiment, the present invention relates to compounds of formula (I-N), of formula (I) and of formula (I-P) in the form of a salt, in particular, a pharmaceutically acceptable salt. It will further be appreciated that, in one embodiment, the invention relates to the example compounds in free base form. In another embodiment, the invention relates to the example compounds in the form of a salt, in particular, a pharmaceutically acceptable salt. Specific embodiments of the compounds of the present invention include: l,l'-((2R,3R)-2,3-dihydroxybutane-l,4-diyl)bis(2-(l-ethyl-3-methyl-lH-pyrazole-5carboxamido)- lH-benzo[d]imidazole-5-carboxamide); (E)-l,l,-(but-2-ene-l,4-diyl)bis(2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-lHbenzo[d] imidazole-5-carboxamide); l,l'-((methylazanodiyl)bis(ethane-2,l-diyl))bis(2-(l-ethyl-3-methyl-l / Apyrazole-5-carboxamido)l / Abenzo[( / |imidazole- 5-carboxamide); l-(4-(5-carbamoyl-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-lH-benzo[d]imidazole-lIF-2019-16742483-APN-ANP#INPI76 Page 76 of 402! ζο[ό]ίηηϊ03ΖθΙ-5-03Γ0οχϊΐ3ΐχ> of methyl; l-(4-(5-carbamoyl-2-(l-ethyl-3-methyl·l·lH-pyrazol·5-carboxamido)-lH-benzo[d]midazol-l¡l)butyl )-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-methoxy-lH-benzo[d]imidazole-5carboxamide; (Ε)-1,1,-(όυΙ-2-6ηο-1,4-όίΐΙ)όϊ5(2-(1-βίίΙ-3-ω6ΰΙ-1Η-ρΐΓ3ζοΙ-5-03Γόοχ3ωΊόο)-7-(3hydroxypropoxy)- lH-benzo[d]imidazole-5-carboxamide); 8-ethyl-10,18-dimethyl-7,20-dioxo-6,7,8,ll,12,13,14,15,20,21,28,29,30,31tetradecahydrobenzo[4,5]imidazo[ l,2-a]benzo[4,5]imidazo[2,l-p]dipyrazolo[5,l-e:4',3'l][l,3,6,15,17]pentaazacyclhenicosine-3,24-dicarboxamide; 8-ethyl-10,18,30-trimethyl-7,20-dioxo-7,8,ll,12,13,14,15,20,21,28,29,30,31,32tetradecahydro-lMbenzo[4, 5]imidazo[2,l-b]benzo[4,5]imidazo[l,2-i]dipyrazolo[5,l-m:4,,3'f][l,3,6,9,ll,14]hexaazadclodocosina- 3,24-dicarboxamide; and l,15-bis(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-8,9,16,17,18,19-hexahydro-7H-6,10dioxa-2,14,15a,19a -tetraazacyclopentadeca[l,2,3-cd:ll,10,9-c'd']diindene-4,12-dicarboxamide; in the form of a free base, or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. Additional embodiments of the compounds of the present invention include: (f)-l.(4.(5-carbamoyl-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-(3-hydroxypropoxy)IH-benzotdlimidazole-l-iDbut^- en-l-iD^-tl-ethyl-S-methyl-lH-pyrazole-S-carboxamidoH-methoxy-lHbenzo[d]imidazole-5-carboxamide; (£)-l,l'-(but-2-ene-l,4-diyl)bis(2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-(3morpholinopropoxy)- lH-benzo[d]imidazole-5-carboxamide); (^-(«-(S^arbamoyl^-yl-ethyl-S-methyl-lH-pyrazole-S-carboxamidoHH-benzotdJimidazole-l¡|)Ρυί-2-6η-1-ϊΙ)-2-(1- βΙίΙ-3-πιβΙίΙ-1Η-ρίΓ3ζοΙ-5-0θΓ0οχ3Πΐΐόο)-7-(3-πιθΓίοΓιηορΓοροχί)-1Ηbenzo[d]imidazole-5-carboxamide; (£)-l-(4.(5-Carbamoyl-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-(3-morpholinopropoxy)lH-benzo[d]imidazole-l -yl)but-2-en-l-yl)-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-methoxy-lHbenzo[d]imidazole-5-carboxamide; (EXi-^-CS-carbamoyl^-Cl-ethyl-S-methyl-lH-pyrazole-S-carboxamidoXlH-benzotdrimidazol-lyl)but-2-en-l-yl)-2-(l-ethyl-3- methyl-lH-pyrazole-5-carboxamido)-7-((4-methoxybendl)oxy)-lHbenzo[d]imidazole-5-carboxamide; (£)-1-(4-(5-ε3ΐΈ)3ΓηοίΙ-2-(1-6ίίΙ-3-ιΤ)6ίίΙ-1Η-ρίΓ3ΖθΙ-5-03Γ0οχ3Γηίόο)-1Η-06ηζο[ό]ίΓ ηί03ζοΙ-1IF-2019- 16742483-APN-ANP#INPI 77 Page 77 of 402 il)but-2-en-l-yl)-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-hydroxy-lH-benzo[d]imidazole-5carboxamide ; l,l'-(2,2,3,3-tetrafluorobutane-l,4-diyl)bis(2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)lH-benzo[d]im dazole-5-carboxamide); (3-(((2)-6-carbamoyl-3-((£)-4-((2)-5-carbamoyl-2-((l-ethyl-3-methyl-lH-pyrazole-5carbonyl)imino )-7-methoxy-2,3-dihydro-lH-benzo[d]imidazol-l-yl)but-2-en-l-yl)-2-((l-ethyl-3-methyl-lHpyrazole-5 ti-tere-butyl -carbonyl)imino)-2,3-dihydro-lH-benzo[d]imidazol-4-yl)oxy)propyl)phosphate; 3-((((2)-6-carbamoyl-3-((£)-4-((¿)-5-carbamoyl-2-((l-ethyl-3-methyl-lHpyrazole) dihydrogenphosphate 5-carbonyl)imino)-7-methoxy-2,3-dihydro-lH-benzo[d]imidazol-l-yl)but-2-en-l-yl)-2-((l-ethyl3-methyl- lH-pyrazole-5-carbonyl)imino)-2,3-dihydro-lH-benzo[d]imidazol-4-yl)oxy)propyl; (£)-7-^οωο-1-(4-(5<3^3ΓηοίΙ-2-(1-6ΐίΙ-3-π61ίΙ-1Η-ρΐΓ3ζοΙ-5οώοχ3Γη^ο)-7-(3methoxypropoxy)-lH-benzo [d]imidazol-l-yl)but-2-en-l-yl)-2-(l-ethyl-3-methyl-lH-pyrazole-5carboxamido)-lH-benzo[d]imidazole-5-carboxamide; (£)-3-(5-carbamoyl-l-(4-(5-carbamoyl-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-(3methoxypropoxy)-lH-benzo [d]imidazol-l-yl)but-2-en-l-yl)-2-(l-ethyl-3-methyl-lH-pyrazole-5carboxamido)-lH-benzo[d]imidazol-7-yl) ethyl propanoate; ethyl acid (£)-3-(5-Carbamoyl-l-(4-(5-carbamoyl-2-(l-ethyl-3-methyl-lH-pyrazole-5carboxamido)-7-(3-methoxypropoxy)-lH -benzo[d]imidazol-l-yl)but-2-en-l-yl)-2-(l-ethyl-3-methyl-lHpyrazole-5-carboxamido)-lH-benzo[d]imidazole-7- il)propanoic; l-^XS-carbamoyl-Z-Cl-ethyl-S-methyl-lH-pyrazole-S-carboxamidoj-lH-benzotdlimidazole-lyl)butyl)-2-(l-ethyl-3-methyl-lH-pyrazole-5 methyl -carboxamido)-lH-benzo[d]imidazole-5-carboxylate; l-(4-(5-carbamoyl-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-lH-benzo[d]imidazol-l¡l)butyl)-2-(l- methyl ethyl-3-methyl-lH-pyrazole-5-carboxamido)-lH-benzo[d]imidazole-5-carboxylate; l-(4-(5-carbamoyl-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-lH-benzo[d]imidazoll-yl)butyl acid)-2-(l-ethyl -3-methyl-lH-pyrazole-5-carboxamido)-lH-benzo[d]imidazole-5-carboxylic acid; (£)-l,l'-(but-2-ene-l,4-diyl)bis(2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-methoxy-lHbenzo[ d]imidazole-5-carboxamide); l / l,-(butane-l,4-diyl)bis(2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-(3-hydroxypropoxy)lH-benzo[d]imidazole -5-carboxamide); (£)-8-ethyl-4,26-bis(3-hydroxypropoxy)-10,18-dimethyl-7 / 20-dioxo6,7,8,ll,12,13,14,15,20,21,28 ,31-dodecahydrobenzo[4,5]imidazo[l,2-a]benzo[4,5]imidazo[2,lp]dipyrazolo[5,l-e:4',3'-l][l,3,6, 15,17]pentaazadchlohenicosine-2,24-dicarboxamide; (f)-l-(4-(5-carbamoyl-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-(3-hydroxypropoxy)lH-benzo[d]imidazole-l -yl)but-2-en-l-yl)-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-(3methoxypropoxy)-lH-benzo[d]imidazole-5- carboxamide; (£)-l-(4-(5-carbamoyl-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-lHbenzo[d]imidazole-lIF-2019-16742483-APN-ANP# INPI 78 Page 78 of 402 il)but-2-en-l-yl)-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-(2-methoxyethoxy)-lHbenzo[d]imidazole-5-carboxamide ; (EXV^but^-ene-M-diiObis^Xl-ethyl-S-methyl-lH-pyrazole-S-carboxamidoXy-isopropoxylH-benzo[d]imidazole-5-carboxamide); (Xy-CbenzyloxO-l-^XS-carbamoyl^-Cl-ethyl-S-methyl-lH-pyrazole-S-carboxamidoXy-methoxylH-benzo[d]imidazol-l-yl)but-2-en-l- il)-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-lHbenzo[d]imidazole-5-carboxamide; (Ζ0-1-(4-(5-€3Γ03ΠΊθίΙ-2-(Γ61ίΙ-3-πΊβΙίΙ-1Η-ρίΓ3ζοΙ-5-θ3Γ0οχ3ΠΊίόο)-1Η06ηζο[ό]ίπΊί ό3ζοΙ-1¡l)but-2-in-l- il)-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-methyl-lHbenzo[d]imidazole-5carboxamide; (E)-l,l'-(but-2-ene-l,4-diyl)bis(7-butoxy-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-lHbenzo[ d]imidazole-5-carboxamide); (E)-l-(4-(5-carbamoyl-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-lHbenzo[d]imidazole-l¡Obut^-en-l-yl ^Xl-ethyl-S-methyl-lH-pyrazole-S-carboxamido^-isopropoxy-lH-benzoCdlimidazole-Scarboxamide; (£)-l,l'-(but-2-ene-l,4-diyl)bis(2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-(3isopropoxypropoxy)- lH-benzo[d]imidazole-5-carboxamide); (E)-2-(l-ethyl·3-methyl-lH-pyrazole-5-carboxamido)-l-(4-(2-(l-ethyl-3-methyl-lH-p razole·5carboxamido)-7-(morpholinomethyl)-lH-benzo[d]imidazol-l-yl)but-2-en-l-yl)-lH-benzo[d]imidazole-5carboxamide; in the form of a free base, or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. One embodiment of the compounds of the present invention includes: (£)-l-(4-(5-carbamo¡l-2-(l-ethyl¡l·3-methyl-lH-pyrazol·5-carboxamido)-lH-benzo[d]imidazole· lil)but-2-en-l-yl)-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-(3-hydroxypropoxy)-lHbenzo[d]imidazole-5-carboxamide ; (Ε)-1-((Ε)-4-((Ε)-5-θθΓΡ3ΓηοίΙ-2-((1-β1ίΙ-3-ΓηβΙϊΙ-1Η-ρΪΓθζοΙ-5-θ8Γ0οηϊΙ)ϊΓηίηο)-2, 3-όίΐΊί0Γθ1Η -06ηζο[ό]ίΓηκ13ζοΙ-1-ίΙ)όυΙ-2-θη-1-ίΙ)-2-((1-θΰΙ-3-ΠΊβΐίΙ-1Η-ρίΓ3ΖθΙ-5-ε8ΓΡοηϊΙ) ίπιίηο)-7-(3hydroxypropoxy) -2,3-dihydro-lH-benzo[d]imidazole-5-carboxamide; (Ζ)-1-((Ε)-4-((Ζ)-5<3Γ08ΓηοίΙ-2-((1-6ΰΙ-3-ΓΤ)βϋΙ-1Η-ρίΓ8ΖθΙ-5-θ3Γΐ3θηίΙ)ϊΓηίηο)-2.3 -ό·|ΐΊϊ0ΓθlH-benzo[d]im¡dazol·l-¡l)but-2-en-l-¡l)-2-((l-ethyl¡l-3-methyl·lH-pyrazole -5-carbon¡l)¡m¡no)-7-(3hydroxypropoxy)-2,3-dihydro-1H-benzo[d]imidazole-5-carboxamide; (EXl-^XS-carbamoyl^-Cl-ethyl-S-methyl-lH-pyrazole-S-carboxamido^XS-hydroxypropoxy)IF-2019-16742483-APN-ANP#INPI 79 Page 79 of 402 IH-benzotdlimidazole-l-iObut-Z-en-l-iD-Z-yl-ethyl-S-methyl-lH-pyrazole-S-carboxamidoj-y-methoxy-lHbenzo[d]imidazole-5-carboxamide; (E)-l-((E)-4-((E)-5-carbamoyl-2-((l-ethyl-3-methyl-lH-pyrazole-5-carbonyl)imino)-7-(3ή^ ΓθχίρΓοροχί)-2,3^ίΚ^Γθ-1Η^Θηζο[4]ΪΓΓ^3ΖθΙ-1-ΐΙ^υ1:-2-6η-1-ίΙ)-2-((1-6ίίΙ-3-Γη6ΐΊΐ -1Η -ρ!Γ3ζοΙ-5carbonyl)imino)-7-methoxy-2,3-dihydro-lH-benzo[d]imidazole-5-carboxamide; (Z)-l-((E)-4-((Z)-5-carbamoyl-2-((l-ethyl-3-methyl-lH-pyrazole-5-carbonyl)imino)-7-(3hydroxypropoxy) -2,3-dihydro-lH-benzo[d]imidazol-l-yl)but-2-en-l-yl)-2-((l-ethyl-3-methyl-lH-pyrazol-5carbonyl)imino) -7-methoxy-2,3-dihydro-lH-benzo[d]imidazole-5-carboxamide; (£)-1-(4-(5οώ3ποίΙ-2-(1-ΘΐίΙ-3-ω6ΐίΙ-1Η-ρίΓ3ζοΙ-5ο±οχ3ηη·^ο)-1Η^βηζο^]ίΠΊ^3ζοΙ-1¡l)but- 2-en-l-yl)-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-(3-morpholinopropoxy)-lHbenzo[d]imidezole-5-cerboxemide; (Ε)-1-((Ε)-4-((Ε)-5-εθΦβπιοίΙ-2-((1-βίίΙ-3-ηΊβνιΙ-1Η-ρίΓθζοΙ-5-θθΓΡοηίΙ)ίΓηΙηο)-2 ,3<ΙίΙ ^ΓθIH-benzotdlimidezol-l-iObut-Z-en-l-iO-Z-iyl-ethyl-S-methyl-lH-pyrazole-S-cerboniOimino)- / -^morpholinopropoxy)-2,3-dihydro-lH- benzo[d]imid8zol-5-C8rbox8mid3; (Ζ)-1-((Ε)-4-((Ζ)-5-οθώθΓηοίΙ-2-((1-6ΐίΙ-3-πΊ61ίΙ-1Η-ρίΓθζοΙ-5-θΒώοηίΙ)ίηηίηο)-2.3· < 1ίΐΊκ1ΓθIH-benzotdiimidazole-l-iObut-Z-en-l-iD-Z-iyl-ethyl-S-methyl-lH-pyrazole-S-carboniOiminoj-Z-iSmorpholinopropoxy)-2,3-dihydro-lH-benzo[d ]imidazole-5-carboxamide; (£)-l-(4-(5-cerbemoyl-2-(l-ethyl-3-methyl-lH-pyrezole-5-cerboxemido)-7-(3-morpholinopropoxy)1Η^6ηζομ]ίπ^3ζοΙ-1 -ίΙ^υΙ-2-θη-1-ίΙ)-2-(1-βϋΙ-3-πθίίΙ-1Η-ρίΓ3ζοΙ-5<3ώοχ3π^ο)-7-Π6ϋοχϊ-1Ηbenzo[d]imid8zol-5-C8rbox8mid8; (E)-l-((E)-4-((E)-5-carbamoyl-2-((l-ethyl-3-methyl-lH-pyrazole-5-carbonyl)imino)-7-(3η' ΐθΓίοΙίηορΓοροχί)-2,3<ϋΙ'ϊκ1Γθ-1Η^θηζο[4]ίη'^ΒζοΙ-1-ίΙ^υΐ-2-6η-1-ίΙ)-2-((1-6ίίΙ -3-Γη6ΐίΙ-1Ηpyrazole -5-carbonyl)imino)-7-methoxy-2,3-dihydro-1H-benzo[d]imidazole-5-carboxamide; (Ζ)-1-((Ε)-4-((Ζ)-5-οβΦ8ηοίΙ-2-((1-6ΰΙ-3-η6ίϊΙ-1Η-ρίΓ8ζοΙ-5-θ3±οηΐΙ)ϊηίηο)-7-( 3morpholinopropoxy)-2,3-dihydro-lH-benzo[d]imidazol-l-yl)but-2-en-l-yl)-2-((l-ethyl-3-methyl-lHpyrezole-5-cerbonyl) imino)-7-methoxy-2,3-dihydro-1H-benzo[d]imidezole-5-cerboxemide; 3-(((2)-6-0ΒΦθΓηοίΙ-3-((£)-4-((2)-5-εβΗ}ΒΓηοίΙ-2-((1-6ΰΙ-3-Γη6ίίΙ-1Ηpyrazole-5-) dihydrogen phosphate carbonyl)imino)-7-methoxy-2,3-dihydro-lH-benzo[d]imidazol-l-yl)but-2-en-l-yl)-2-((l-ethylS-methyl-lH- pyrazole-S-carboniOiminoyZ^-dihydro-lH-benzotdJimidazole^-iOoxyjpropyl; dihydrogenphosphate -en-l-yl)-2-(l-ethyl-3-methyl-lH-pyrezole-5carboxamido)-lH-benzo[d]imidazol-7-yl)oxy)propyl; 3-(((Ζ)-6-θ3ώ3ΠΊθ'ιΙ-3-((Ε)-4-((Ζ)-5-θ3ή53ΓηοίΙ-2-((1-61ίΙ-3-ΓηβΟΙ-1ΗρίΓ3ΖθΙ-5-) dihydrogen phosphate 03^)οηίΙ)ίπΊίηο)-7-Γηθίοχί-2,3^ί|·|^Γθ-1Η^6ηζο[4]ίΓηκ13ζοΙ-1-ΐΙ^υ1-2-6η-1-ιΙ)-2-(( 1-θίίΙ3-methyl-lH-pyrazol-5-c8rbonyl)imino)-2,3-dihydro-lH-benzo[d]imid8zol-4-yl)oxy)propyl; or a tsutomer thereof; or joins salt thereof, in psrticuler joins it fermeceutically IF-2019-16742483-APN-ANP#INPI θ° Page 80 of 402 acceptable of them. In one embodiment, the compounds of formula (I-N), of formula (I) or of formula (I-P) are not the following compounds: (£)-l-(4-(5-carbamoyl-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-lH-benzo[d]imidazol-l¡l)but-2- en-l-yl)-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-(3-hydroxypropoxy)-lHbenzo[d]imidazole-5-carboxamide; (Ej-l-CCEH-KEj-S-carbamoyl^-Kl-ethyl-S-methyl-lH-pyrazole-S-carboniDiminoX^S-dihydro1Η-όεηζο[ό]^ϊ03ζοΙ-1-ίΙ)όυν2-6η-1 -!Ι)-2-((1-θνιΙ-3-Γη6ΐϊΙ-1Η··ρίΓ3ΖθΙ-5-03Γ0οηίΙ)ϊΓηίηο)-7-(3hydroxypropoxy)-2,3-dihydro-lH-benzo[d]imidazole-5 -carboxamide; (Z)-l-((E)-4-((Z)-5-carbamoyl-2-((l-ethyl-3-methyl-lH-pyrazole-5-carbonyl)imino)-2,3-dihydro1Η ··όθηζο[ό]ίΓηί03ΖθΙ-1-ίΙ)όυί-2-θη-1··ϊΙ)-2-((1-6ίίΙ-3-ΓηθϋΙ-1Η-ρίΓ3ζοΙ-5-θ3Γ0οηί Ι)ίιτιίηο)-7-( 3hydroxypropoxy)-2,3-dihydro-1H-benzo[d]imidazole-5-carboxamide; (£)-l-(4-(5-carbamoyl-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-(3-hydroxypropoxy)lH-benzotdlimidazole-l-iObut^- en-l-iO^Xl-ethyl-S-methyl-lH-pyrazole-S-carboxamidoyZ-methoxy-lHbenzo[d]imidazole-5-carboxamide; (E)-l-((E)-4-((E)-5-carbamoyl-2-((l-ethyl-3-methyl-lH-pyrazol-5-carbonyl)imino)-7-(3h¡ droxypropoxy¡)-2,3-di¡hydro-lH-benzo[d]ímidazol·l-¡l)but-2-en-l-¡l)-2-((l-ethyl¡l· 3-methyl-lH-pyrazole-5carbonyl)imino)-7-methoxy-2,3-dihydro-lH-benzo[d]imidazole-5-carboxamide; (ZH-GEH-iiZyS-carbamoyl^-tfl-ethyl-S-methyl-lH-pyrazole-S-carboniOiminoH-iShydroxypropoxy)-2,3-dihydro-lH-benzo[d]imidazol-l-yl)but-2 -en-l-yl)-2-((l-ethyl-3-methyl-lH-pyrazole-5carbonyl)imino)-7-methoxy-2,3-dihydro-lH-benzo[d]imidazole-5-carboxamide ; (E)-l-(4-(5-carbamoyl-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-lH-benzo[d]imidazol-lyl)but-2-en- l-¡l)-2-(l-ethyl·3-methyl·lH-pyrazol-5-carboxamido)-7-(3-morpholinopropoxy)-lHbenzo[d]imidazole-5-carboxamide; (E)-l-((E)-4-((E)-5-carbamoyl-2-((l-ethyl-3-methyl-lH-pyrazol-5-carbonyl)imino)-2,3-dihydroIH -benzotdlimidazol-l-iDbut-Z-en-l-iiyZ-tfl-ethyl-S-methyl-lH-pyrazole-S-carboniOiminop-tSmorpholinopropoxy)-2,3-dihydro-lH-benzo[d]imidazole-5- carboxamide; (Z)-l-((E)-4-((Z)-5-carbamoyl-2-((l-ethyl-3-methyl-lH-pyrazole-5-carbonyl)imino)-2,3-dihydroIH -benzoldJimidazole-l-iObut-Z-en-l-iO-Z-iyl-ethyl-S-methyl-lH-pyrazole-S-carboniDiminoJ-Z-iSmorpholinopropoxy)-2,3-dihydro-lH-benzo[d] imidazole-5-carboxamide; (^-l-^XS-carbamoyl-Z-Cl-ethyl-S-methyl-lH-pyrazole-S-carboxamidoj-Z-p-morpholinopropoxy)IH-benzotojimidazol-l-iObut-Z-en-l-iD-Z- yl-etií-S-methyl-lH-pyrazole-S-carboxamidoj-Z-methoxy-lHbenzo[d]imidazole-5-carboxamide;!(Ej-l-iCEj^CiEJ-S-carbamoyl-Z-iyl-ethyl- S-methyl-lH-pyrazole-S-carboniOiminoj-y-iSIF-2019-16742483-APN-ANP#INPI θ1 Page 81 of 402 morpholinopropoxy)-2,3-dihydro-lH-benzo[d]imidazol-l-yl)but-2-en-l-yl)-2-((l-ethyl-3-methyl-lHpyrazole- 5-carbonyl)imino)-7-methoxy-2,3-dihydro-1H-benzo[d]imidazole-5-carboxamide; (Z)-l-((E)-4-((Z)-5-cerbemoyl-2-((l-ethyl-3-methyl-lH-pyrezole-5-cerbonyl)imino)-7-(3morpholinopropoxy) -2,3-dihydro-lH-benzo[d]imidazol-l-yl)but-2-en-l-yl)-2-((l-ethyl-3-methyl-lHpyrazole-5-carbonyl)imino) -7-methoxy-2,3-dihydro-lH-benzo[d]imidazole-5-carboxamide; 3-(((z)-6-cerbemoyl-3-((£)-4-((z)-5-cerbemoyl-2-((l-ethyl-3-methyl-lHpyrazole-5-carbonyl) dihydrogenphosphate imino)-7-methoxy-2,3-dihydro-lH-benzo[d]imidazol-l-yl)but-2-en-l-yl)-2-((l-ethyl3-methyl-lH-pyrezole- 5-cerbonyl)imino)-2,3-dihydro-1H-benzo[d]imidezol-4-yl)oxy)propyl; (E)-3-((5-cerbemoyl-l-(4-(5-cerbemoyl-2-(l-ethyl-3-methyl-lH-pyrezole·5-cerboxemido)-7-methoxy-lH-dihydrogenphosphate benzo[d]imidezol-l-yl)but-2-en-l-yl)-2-(l-ethyl-3-methyl-lH-pyrezol-5cerboxemido)-lH-benzo[d]imidezol-7-yl )oxy)propyl; 3-(((Z)-6-cerbemoyl-3-((E)-4-((Z)-5-cerbemoyl-2-((l-ethyl-3-methyl-lHpyrezole-5-cerbonyl) dihydrogenphosphate imino)-7-methoxy-2,3-dihydro-lH-benzo[d]imidezol-l-yl)but-2-en-l-yl)-2-((l-ethylS-methyl-lH-pyrazole- S-carboniOiminoJ-Z^-dihydro-lH-benzoIdjimidezole^-iOoxOpropyl; or a teutomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In a reappraisal, the compounds of formule (I-N), formule (I) or formule (I-P) are not the following compounds: (E)-l-(4-(5-cerbemoyl-2-(l-ethyl¡l-3-met¡l-lH-pyrezole-5-cerboxemido)-lH-benzo[d]¡midezole-l¡l )but-2-en-l-yl)-2-(l-ethyl-3-methyl-lH-pyrezole-5-cerboxemido)-7-(3-hydroxypropoxy)-lHbenzo[d]imidezole- 5-cerboxemide; (E)-l-((E)-4-((E)-5-cerbamoyl-2-((l-ethyl-3-methyl-lH-pyrezole-5-cerbonyl)imino)-2,3-dihydrolH -benzo[d]imidezol-l-yl)but-2-en-l-yl)-2-((l-ethyl-3-methyl-lH-pyrezol-5-cerbonyl)imino)-7-(3hydroxypropoxy) -2,3-dihydro-lH-benzo[d]imidezole-5-cerboxemide; (Ζ)-1-((Ε)-4-((Ζ)-5-ε3Γ03ΠΐοίΙ-2-((1-β1ίΙ-3-ΓηβΰΙ-1Η-ρίΓ3ΖθΙ-5-θ3Γΐχ>η·|Ι)ίΓη·| ηο)-2,3^ΐΐΊ^ΓθlH-benzo[d]imidazol-l-yl)but-2-en-l-yl)-2-((l-ethyl-3-methyl-lH-pyrazole-5- carbonyl)imino)-7-(3hydroxypropoxy)-2,3-dihydro-1H-benzo[d]imidazole-5-carboxamide; or a teutomer thereof; or one of them, in particular one of the fermeceutically acceptable ones of the same. In a reappraisal, the compounds of formule (I-N), formule (I) or formule (I-P) are not the following compounds: (£)-l-(4-(5-carbamoyl-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-(3-hydroxypropoxy)IF-2019-16742483-APN-ANP #INPI 82 Page 82 of 402 lH-benzo[d]imidazol-l-yl)but-2-en-l-yl)-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-methoxy -lHbenzo[d]imidazole-5-carboxamide; (E)-l-((E)-4-((E)-5-carbamoyl-2-((l-ethyl-3-methyl-lH-pyrazole-5-carbonyl)imino)-7-(3hydroxypropoxy) -2,3-dihydro-lH-benzo[d]imidazol-l-yl)but-2-en-l-yl)-2-((l-ethyl-3-methyl-lH-pyrazol-5carbonyl)imino) -7-methoxy-2,3-dihydro-lH-benzo[d]imidazole-5-carboxamide; (Z)-l-((E)-4-((Z)-5-carbamoyl-2-((l-ethyl-3-methyl-lH-pyrazole-5-carbonyl)imino)-7-(3ΐΊ^ ΓθχίρΓοροχί)-2,3^ίΐΊκΐΓθ-1Η-όβηζο[^]ίηη^3ζοΙ-1-ίΙ)όυυ2-6η-1-ίΙ)-2-((1-βίίΙ-3-Γη 6ΐίΙ-1Η-ρϊΓβζοΙ-5carbonyl) imino)-7-methoxy-2,3-dihydro-1H-benzo[d]imidazole-5-carboxamide; or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment, the compounds of formula (I-N), of formula (I) or of formula (I-P) are not the following compounds: (£)-l-(4-(5-carbamoyl-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-lH-benzo[d]¡m¡dazol-lyl)but -2-en-l-yl)-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-(3-morphopropoxy)-lHbenzo[d]imidazole-5-carboxamide; (E)-l-((E)-4-((E)-5-carbamoyl-2-((l-ethyl-3-methyl-lH-pyrazole-5-carbonyl)imino)-2,3-dihydro1Η -όθηζο[ό]ίΓηί03ΖθΙ-1-ίΙ)όυυ2-θη-1-ίΙ)-2-((1-6ίίΙ-3-ηΊ6ΐίΙ-1Η-ρίΓ3ζοΙ-5-ε3Γ0οηίΙ )ίΠΊίηο)-7-(3morpholinopropoxy)-2 ,3-dihydro-lH-benzo[d]imidazole-5-carboxamide; (Z)-l-((E)-4-((Z)-5-carbamoyl-2-((l-ethyl-3-methyl-lH-pyrazole-5-carbonyl)imino)-2,3-dihydro1Η -06ηζο[ό]!ηηί03ζοΙ-1-ίΙ)όυί-2-6η-1-ΐΙ)-2-((1-6ίίΙ-3-Γη6ΐίΙ-1Η-ρίΓ3ζοΙ-5-03Γ0οηίΙ)ί ΠΊίηο)-7-(3morpholinopropoxy )-2,3-dihydro-lH-benzo[d]imidazole-5-carboxamide; or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In a reappraisal, the compounds of formule (I-N), formule (I) or formule (I-P) are not the following compounds: (£)-l-(4-(5-carbamoyl-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-(3-morpholinopropoxy¡)lH-benzo[ d]imidazol-l-yl)but-2-en-l-yl)-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7-methoxy-lHbenzo[d]imidezole-5 -cerboxem¡de; (E)-l-((E)-4-((E)-5-cerbemoyl-2-((l-ethyl-3-methyl-lH-pyrazole-5-cerbonyl)imino)-7-(3morpholinopropoxy) -2,3-dihydro-lH-benzo[d]imidazol-l-yl)but-2-en-l-yl)-2-((l-ethyl-3-methyl-lHpyrazole-5-carbonyl)imino) -7-methoxy-2,3-dihydro-lH-benzo[d]imidazole-5-carboxamide; (Z)-l-((E)-4-((Z)-5-carbamoyl-2-((l-ethyl-3-methyl-lH-pyrazole-5-carbonyl)imino)-7-(3IF- 2019-16742483-APN-ANP#INPI θ3 Page 83 of 402 morpholinopropoxy)-2,3-dihydro-lH-benzo[d]imidazol-l-yl)but-2-en-l-yl)-2-((l-ethyl-3-methyl-lHpyrazole- 5-carbonyl)imino)-7-methoxy-2,3-dihydro-1H-benzo[d]imidazole-5-carboxamide; or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment, the compounds of formula (1-N), of formula (I) or of formula (I-P) are not the following compounds: 3-(((2)-6-carbamo¡l-3-((£)-4-((2)-5-carbamo¡l-2-((l-ethyl-3-methyl-methyl) dihydrogenphosphate lHpyrazole-5-carbonyl)imino)-7-methoxy-2,3-dihydro-lH-benzo[d]imidazol-l-yl)but-2-en-l-yl)-2-((l-ethyl3- methyl-1H-pyrazol-5-carbonyl)imino)-2,3-dihydro-1H-benzo[d]imidazol-4-yl)oxy)propyl; (E)-3-((5-carbamoyl-l-(4-(5-carbamoyl-2-(l-ethyl-3-methyl-lH-pyrazole5-carboxamido)-7-methoxy-lH-benzo[ dihydrogenphosphate d]imidazol-l-yl)but-2-en-l-yl)-2-(l-ethyl-3-methyl-lH-pyrazole-5carboxamido)-lH-benzo[d]imidazol-7-yl)oxy )propyl; 3-(((Z)-6-carbamoyl-3-((E)-4-((Z)-5-carbamoyl-2-((l-ethyl-3-methyl-lHpyrazole-5-carbonyl) dihydrogenphosphate) imino)-7-methoxy-2,3-dihydro-lH-benzo[d]imidazol-l-yl)but-2-en-l-yl)-2-((l-ethyl3-methyl-lH-pyrazole- 5-carbonyl)imino)-2,3-dihydro-1H-benzo[d]imidazol-4-yl)oxy)propyl; or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment, the compound of formula (1-N), of formula (I) or of formula (1-P) is (£)-l-(4-(5-Carbamoyl-2-(l-ethyl-3-methyl-lH -pyrazole-5-carboxamido)-lH-benzo[d]irnidazol-l-yl)but2-en-l-yl)-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7 -(3-hydroxypropoxy)-lH-benzo[d]imidazole5-carboxamide or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment, the compound of formula (1-N), of formula (I) or of formula (1-P) is IF-2019-16742483-APN-ANP#INPI84 Page 84 of 402 (E)-l-((E)-4-((E)-5-carbamoyl-2-((l-ethyl-3-methyl-lH-pyrazole-5-carbonyl)imino)-2 ,3-dihydro-lHbenzo[d]imidazol-l-yl)but-2-en-l-yl)-2-((l-ethyl-3-methyl-lH-pyrazole-5-carbonyl)imino)-7 -(3hydroxypropoxy)-2,3-dihydro-lH-benzo[d]imidazole-5-carboxamide or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment, the compound of formula (1-N), of formula (I) or of formula (1-P) is (Z)-l-((E)-4-((Z)-5-carbamoyl-2-(( l-ethyl-3-methyl-lH-pyrazol-5-carbonyl)imino)-2,3-dihydro-lH10 benzoidjimidazoi-l-iObut-Z-en-l-iO-Z-tfl-ethyl-S-methyl- lH-pyrazole-S-carboniOimino)-?-^hydroxypropoxy)-2,3-dihydro-lH-benzo[d]imidazole-5-carboxamide or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment, the compound of formula (1-N), of formula (I) or of formula (1-P) is (£)-l-(4-(5-carbamoyl-2-(l-ethyl-3-methyl-lH -pyrazole-5-carboxamido)-7-(3-hydroxypropoxy)-lHbenzo[d]imidazol-l-yl)but-2-en-l-yl)-2-(l-ethyl-3-methyl-lH- pyrazole-5-carboxamido)-7-methoxy-lHbenzo[d]imidazole-5-carboxamide IF-2019-16742483-APN-ANP#INPI85 Page 85 of 402 or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment, the compound of formula (l-N), of formula (I) or of formula (l-P) is (EJ-l-CCEj-^iiEJ-S-carbamoyl-Z-iCl-ethyl-S-methyl-lH- pyrazole-S-carboniOiminoj-y-CS-hydroxypropoxy)2,3-dihydro-lH-benzo[d]imidazol-l-yl)but-2-en-l-yl)-2-((l-ethyl-3 -methyl-lH-pyrazole-5-carbonyl)imino)7-methoxy-2,3-dihydro-lH-benzo[d]imidazole-5-carboxamide or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment, the compound of formula (1-N), of formula (I) or of formula (1-P) is (Z)-l-((E)-4-((Z)-5-carbamoyl-2-(( l-ethyl-3-methyl-lH-pyrazol-5-carbonyl)imino)-7-(3-hydroxypropoxy)15 2,3-dihydro-lH-benzo[d]imidazol-l-yl)but-2-en -l-yl)-2-((l-ethyl-3-methyl-lH-pyrazol-5-carbonyl)imino)7-methoxy-2,3-dihydro-lH-benzo[d]imidazole-5-carboxamide IF-2019-16742483-APN-ANP#INPI86 Page 86 of 402 or or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment, the compound of formula (1-N), of formula (I) or of formula (1-P) is (£)-l-(4-(5-carbamoyl-2-(l-ethyl-3-methyl-lH -pyrazole-5-carboxamido)-lH-benzo[d]imidazol-l-yl)but2-en-l-yl)-2-(l-ethyl-3-methyl-lH-pyrazole-5-carboxamido)-7 -(3-morpholinopropoxy)-lHbenzo[d]imidazole-5-carboxamide or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment, the compound of formula (1-N), of formula (I) or of formula (1-P) is (E)-l-((E)-4-((E)-5-carbamoyl-2-(( l-ethyl-3-methyl-lH-pyrazol-5-carbonyl)imino)-2,3-dihydro-lH15 benzo[d]imidazol-l-yl)but-2-en-l-yl)-2-( (l-ethyl-3-methyl-lH-pyrazol-5-carbonyl)imino)-7-(3morpholinopropoxy)-2,3-dihydro-lH-benzo[d]imidazole-5-carboxamide IF-2019-16742483-APN-ANP#INPI87 Page 87 of 402 .0 or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment, the compound of formula (1-N), of formula (I) or of formula (1-P) is (Z)-l-((E)-4-((Z)-5-carbamoyl-2-(( l-ethyl-3-methyl-lH-pyrazol-5-carbonyl)imino)-2,3-dihydro-lHbenzo[d]imidazol-l-yl)but-2-en-l-yl)-2-(( l-ethyl-3-methyl-lH-pyrazol-5-carbonyl)imino)-7-(3morpholinopropoxy)-2,3-dihydro-lH-benzo[d]imidazole-5-carboxamide or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment, the compound of formula (1-N), of formula (I) or of formula (1-P) is (£)-l-(4-(5-carbamoyl-2-(l-ethyl-3-methyl-lH -pyrazole-5-carboxamido)-7-(3-morpholinopropoxy)-lHbenzo[d]imidazol-l-yl)but-2-en-l-yl)-2-(l-ethyl-3-methyl-lH- pyrazole-5-carboxamido)-7-methoxy-lHbenzo[d]imidazole-5-carboxamide IF-2019-16742483-APN-ANP#INPI θθ Page 88 of 402 or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment, the compound of formula (1-N), of formula (I) or of formula (1-P) is (E)-l-((E)-4-((E)-5-carbamoyl-2-(( l-ethyl-3-methyl-lH-pyrazol-5-carbonyl)imino)-7-(3morpholinopropoxy)-2,3-dihydro-lH-benzo[d]imidazol-l-yl)but-2-en-l -yl)-2-((l-ethyl-3-methyl-lHpyrazole-5-carbonyl)imino)-7-methoxy-2,3-dihydro-lH-benzo[d]imidazole-5-carboxamide or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment, the compound of formula (1-N), of formula (I) or of formula (1-P) is (Z)-l-((E)-4-((Z)-5-carbamoyl-2-(( l-ethyl-3-methyl-lH-pyrazol-5-carbonyl)imino)-7-(3morpholinopropoxy)-2,3-dihydro-lH-benzo[d]imidazol-l-yl)but-2-en-l -yl)-2-((l-ethyl-3-methyl-lHpyrazole-5-carbonyl)imino)-7-methoxy-2,3-dihydro-lH-benzo[d]imidazole-5-carboxamide IF-2019-16742483-APN-ANP#INPI89 Page 89 of 402 or or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment, the compound of formula (1-N), of formula (I) or of formula (1-P) is 3-(((2)-6-carbamoyl-3-((£)-4-((2) dihydrogen phosphate )-5-carbamoyl-2-((l-ethyl-3-methyl-lH-pyrazol5-carbonyl)imino)-7-methoxy-2,3-dihydro-lH-benzo[d]imidazol-l-yl)but -2-en-l-yl)-2-((l-ethyl-3-methyllH-pyrazol-5-carbonyl)imino)-2,3-dihydro-lH-benzo[d]imidazol-4-yl)oxy )propyl or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment, the compound of formula (1-N), of formula (I) or of formula (1-P) is (E)-3-((5-carbamoyl-l-(4-(5-carbamoyl-) dihydrogen phosphate). 2-(l-ethyl-3-methyl-lH-pyrazole-515 carboxamido)-7-methoxy-lH-benzo[d]imidazol-l-yl)but-2-en-l-yl)-2- (l-ethyl-3-methyl-lH-pyrazole-5carboxamido)-lH-benzo[d]imidazol-7-yl)oxy)propyl IF-2019-16742483-APN-ANP#INPI90 Page 90 of 402 or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. In one embodiment, the compound of formula (l-N), of formula (I) or of formula (l-P) is 3-(((Z)-6-carbamoyl-3-((E)-4-(( Z)-5-carbamoyl-2-((l-ethyl-3-methyl-lHpyrazole-5-carbonyl)imino)-7-methoxy-2,3-dihydro-lK-benzo[d]imidazole-l- il)but-2-en-l-yl)-2-((l-ethyl3-methyl-lH-pyrazol-5-carbonyl)imino)-2,3-dihydro-lH-benzo[d]imidazol-4- yl)oxy)propyl or a tautomer thereof; or a salt thereof, in particular a pharmaceutically acceptable salt thereof. Compounds of the present invention may contain one or more asymmetric centers (also referred to as a chiral center), such as a chiral carbon, or a SO-chiral moiety. Compounds of the present invention containing one or more chiral centers may be present in the form of racemic mixtures, diastereomeric mixtures, enantiomerically enriched mixtures, diastereomerically enriched mixtures, or in the form of enantiomerically or diastereomerically pure individual stereoisomers. The stereochemistry of the chiral center present in the compounds of the present invention is generally represented in the names of the compounds and / or in the chemical structures illustrated herein. In cases where the stereochemistry of a chiral center present in a compound of the present invention or in IF-2019-16742483-APN-ANP#INPI91 Page 91 of 402 any chemical structure illustrated herein, the structure is intended to encompass any stereoisomer and all mixtures thereof. Accordingly, the present invention encompasses all isomers of the compounds of formula (I-N), (I-P) or (I), and salts thereof, whether in the form of individual isomers isolated such that they are substantially free of each other. isomer (i.e. pure) or in the form of mixtures (i.e. racemates and racemic mixtures). An individual isomer isolated such that it is substantially free of the other isomer (i.e., pure) may be isolated such that less than 10%, particularly less than about 1%, for example less than about 0, 1% of the other isomer. Individual stereoisomers of a compound of the present invention can be resolved (or mixtures of stereoisomers enriched) using methods known to those skilled in the art. For example, such resolution may be carried out (1) by the formation of salts, complexes or other stereoisomeric derivatives; (2) by selective reaction with a stereoisomer-specific reagent, for example, by enzymatic oxidation or reduction; or (3) by gas-liquid or liquid chromatography in a chiral environment, for example, on a chiral support, such as silica with a chiral ligand attached or in the presence of a chiral solvent. It will be appreciated that in cases where the desired stereoisomer is converted to another chemical entity by one of the separation procedures described above, an additional step is necessary to release the desired form. Alternatively, specific stereoisomers can be synthesized by asymmetric synthesis using optically active reagents, substrates, catalysts or solvents, or by converting one enantiomer to the other by asymmetric transformation. The invention also includes various deuterated forms of the compounds of the present invention. Each available hydrogen atom bonded to a carbon atom can be independently replaced with a deuterium atom. One of ordinary skill in the art will know how to synthesize deuterated forms of the compounds of the present invention. For example, α-deuterated o-amino acids are commercially available or can be prepared by conventional techniques (see, for example: Elemes, Y. and Ragnarsson, U. J. Chem. Soc., Perkin Trans. 1,1996, 6, 537- 40). The use of such compounds may allow the preparation of compounds in which the hydrogen atom in a chiral center is replaced with a deuterium atom. Other commercially available deuterated starting materials may be used in the preparation of deuterated analogues of the compounds of the present invention (see, for example: methyl-c^-amine available from Aldrich Chemical Co., Milwaukee, Wis.), or they may synthesized using conventional techniques employing deuterated reagents (e.g., by reduction using lithium aluminum deuteride or sodium borodeuteride or by metal-halogen exchange followed by inactivation with D2O or IF-2019-16742483-APN-ANP#INPI92 Page 92 of 402 methanol-í / j). Suitable pharmaceutically acceptable salts of the compounds of formula (IN), (1-P) or (I) may include acid addition salts or base addition salts. For reviews of suitable pharmaceutically acceptable salts see Berge etaL, J. Pharm. Sci., 66:1-19, (1977) and P. H. Stahl and C. G. Wermuth, Eds., Handbook of Pharmaceutical Salts: Properties, Selection and Use, We¡nhe¡m / Zür¡ch:Wiley-VCH / VHCA (2002 ). Salts of compounds of formula (l-N), (l-P) or (I) containing a basic amine or other basic functional group can be prepared by any suitable method known in the art, such as treatment of the free base with an inorganic acid or suitable organic. Examples of pharmaceutically acceptable salts formed in this way include acetate, adipate, ascorbate, aspartate, benzenesulfonate, benzoate, camphorate, camphorsulfonate (camsylate), caprate (decanoate), caproate (hexanoate), caprylate (octanoate), carbonate, bicarbonate, cinnamate , citrate, cyclamate, dodecyl sulfate (stolate), ethane-1,2disulfonate (edisylate), ethanesulfonate (esylate), formate, fumarate (hemifumarate, etc.), galactarate (mucate), gentisate (2,5-dihydroxybenzoate), glucoheptonate ( gluceptate), gluconate, glucuronate, glutamate, glutarate, glycerophosphorate, glycolate, hippurate, hydrobromide, hydrochloride (dihydrochloride, etc.), hydroiodide, isobutyrate, lactate, lactobionate, laurate, maleate, malate, malonate, mandelate, methanesulfonate (mesylate), naphthalene-1,5disulfonate (napadisylate), naphthalene-sulfonate (napsylate), nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, phosphate (diphosphate, etc.), proprionate, pyroglymate, salicylate, sebacate, stearate, succinate , sulfate, tartrate, thiocyanate, p-toluenesulfonate (tosylate), undecylenate, 1hydroxy-2-naphthoate, 2,2-dichloroacetate, 2-hydroxyethanesulfonate (isethionate), 2-oxogl utarate, 4acetamidobenzoate, and 4-aminosalicylate. Salts of the disclosed compounds containing a carboxylic acid or other acidic functional group can be prepared by reacting with a suitable base. Said pharmaceutically acceptable salt may be prepared with a base that provides a pharmaceutically acceptable cation, including alkali metal salts (especially sodium and potassium), alkaline earth metal salts (especially calcium and magnesium), aluminum salts and ammonium salts, as well as salts prepared from physiologically acceptable organic bases, such as trimethylamine, triethylamine, morpholine, pyridine, piperidine, picoline, dicyclohexylamine, / V, / V-dibenzylethylenediamine, 2-hydroxyethlamine, d / s-(2-hydroxyethyl )amine, tri-(2hydroxyethyl)amine, procaine, dibenzylpiperidine, dehydroabietylamine, N,Nbisdehydroabietylamine, glucamine, / V-methylglucamine, colidine, choline, quinine, quinoline, and basic amino acids, such as lysine and arginine. The invention includes within its scope all possible stoichiometric and non-stoichiometric forms of salts (for example, hydrobromide, dihydrobromide, fumarate, IF-2019-16742483-APN-ANP#INPI 93 Page 93 of 402 hemifumarate, etc.) of the compounds of formula (I-N), (I-P) or (I). Where a disclosed compound or salt is named or illustrated by its structure, it should be understood that the compound or salt, including solvates (in particular, hydrates) thereof, may exist in crystalline forms, non-crystalline forms, or a mixture. from the same. The compound or salt, or solvates (particularly hydrates) thereof, may also show polymorphism (i.e., the ability to occur in different crystalline forms). These different crystal forms are typically known as polymorphs. It should be understood that the invention includes all polymorphs of any compound of the present invention, for example, all polymorphic forms of any compound named or illustrated by its structure herein, including any salt and / or solvate (in particular, hydrates) of the same. The polymorphs have the same chemical composition but differ in their distribution, geometric arrangement, and other properties descriptive of the crystalline solid state. Polymorphs, therefore, can have different physical properties such as shape, density, hardness, deformability, stability, and dissolution properties. Typically, polymorphs show different melting points, IR spectra, and X-ray powder diffraction patterns, which can be used for their identification. It will be appreciated that different polymorphs can be produced, for example, by changing or adjusting the conditions used when crystallizing / recrystallizing the compound. Polymorphic forms can be characterized and differentiated using a number of conventional analytical techniques, including, but not limited to, X-ray powder diffraction (XRPD) patterns, infrared (IR) spectra, Raman spectra, differential scanning calorimetry (DSC). , thermogravimetric analysis (TGA) and solid state nuclear magnetic resonance (SSNMR). One skilled in the art will appreciate that pharmaceutically acceptable solvates (in particular, hydrates) of a compound of formula (I-N), (I-P) or (I), including pharmaceutically acceptable solvates of a pharmaceutically acceptable salt of a compound of formula (I-N ), (I-P) or (I), can be formed when solvent molecules are incorporated into the crystal lattice during crystallization. Solvates may involve non-aqueous solvents, such as ethanol, or may involve water as a solvent that is incorporated into the crystal lattice. Solvates where water is the solvent that is incorporated into the crystal lattice are typically referred to as hydrates. The present invention includes within its scope all possible stoichiometric and non-stoichiometric salt and / or hydrate forms. Salts and solvates (e.g., hydrates and salt hydrates) of the compounds of the invention that are suitable for use in medicine are those where the counterion or associated solvent is pharmaceutically acceptable. They are within the scope IF-2019-16742483-APN-ANP#INPI94 Page 94 of 402 of the present invention those salts that have non-pharmaceutically acceptable counterions, for example, for use as intermediates in the preparation of other compounds of the invention. Typically, a pharmaceutically acceptable salt can be readily prepared by use of a desired acid or base, as appropriate. The resulting salt may crystallize or precipitate from a solution, or formed by grinding, and may be recovered by filtration, or by evaporation of the solvent. Because the compounds of the present invention are intended for use in pharmaceutical compositions, it will be readily understood that each is preferably provided in substantially pure form, for example, at least 60% pure, more suitably at least 75% pure. % pure and preferably at least 85% pure, especially at least 98% pure (% are by weight). Impure preparations of the compounds can be used to prepare the purer forms used in pharmaceutical compositions. The invention encompasses all prodrugs of the compounds of the present invention, which upon administration to the recipient are capable of providing (directly or indirectly) a compound of the present invention, or a metabolite or active moiety thereof. Said derivatives are recognizable by experts in the field, without unnecessary experimentation. However, reference is made to the teaching of Burger's Medicinal Chemistry and Drug Discovery, 5th Edition, Vol 1: Principles and Practice, which is incorporated herein by reference in its scope of teaching said derivatives. Furthermore, it should be understood that the present invention includes within its scope all tautomeric or isomeric forms of any free base form of the compounds of the present invention as well as all stoichiometric and non-stoichiometric salt forms. The compounds of the invention are useful for the treatment or prevention of diseases and disorders in which modulation of STING is beneficial. Such STING-mediated diseases and disorders include inflammation, allergic and autoimmune diseases, infectious diseases, cancer, and precancerous syndromes. The compounds of the invention are also useful as an immunogenic composition or as a vaccine adjuvant. Accordingly, the invention relates to a method for modulating STING comprising contacting a cell with a compound of the invention. One aspect of the invention provides methods of treating or preventing STING-mediated diseases and disorders, in which STING agonism is beneficial. Illustrative diseases / disorders include, but are not limited to, cancer, infectious diseases (e.g., HIV, HBV, HCV, HPV, and influenza), vaccine adjuvant. IF-2019-16742483-APN-ANP#INPI 95 Page 95 of 402 In one embodiment, the present invention provides a compound of the invention for use in therapy. The present invention also provides a compound of formula (1-N), (1-P) or (I), or a pharmaceutically acceptable salt thereof, for use in therapy. The present invention particularly provides a compound of formula (l-N), (l-P) or (I), or a pharmaceutically acceptable salt thereof, for use in the treatment of a STING-mediated disease or disorder. The present invention also provides a compound of formula (1-N), (1-P) or (I), or a pharmaceutically acceptable salt thereof, for use as a vaccine adjuvant. Therefore, there is also provided an immunogenic composition or a vaccine adjuvant comprising a compound of formula (1-N), (1-P) or (I), or a pharmaceutically acceptable salt thereof. In a further embodiment of the invention, there is provided a composition comprising a compound of formula (1-N), (1-P) or (I), or a pharmaceutically acceptable salt thereof, and one or more immunostimulating agents. In another embodiment, the present invention provides a compound of the invention for use in the treatment of a STING-mediated disease or disorder and / or for use as an immunogenic composition or as a vaccine adjuvant. In another embodiment, the present invention provides a compound of formula (l-N), (l-P) or (I), or a pharmaceutically acceptable salt thereof, for use in alleviating organ injury or damage sustained as a result of a STING-mediated disease or disorder. The invention further provides the use of a compound of the invention in the manufacture of a medicament for the treatment of a STING-mediated disease or disorder. The invention further provides the use of a compound of formula (l-N), (l-P) or (I), or a salt thereof, in particular a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment of a disease or STING-mediated disorder, for example, the diseases and disorders cited herein. The invention further provides the use of a compound of formula (1-N), (1-P) or (I), or a salt thereof, in particular a pharmaceutically acceptable salt thereof, in the manufacture of a vaccine. Furthermore, there is provided the use of a compound of formula (l-N), (l-P) or (I), or a pharmaceutically acceptable salt thereof, for the manufacture of an immunogenic composition comprising an antigen or an antigenic composition, for the treatment or disease prevention. Furthermore, there is provided the use of a compound of formula (l-N), (l-P) or (I), or a pharmaceutically acceptable salt thereof, for the manufacture of a vaccine composition comprising an antigen or an antigenic composition, for the treatment or prevention of diseases. In another embodiment, the invention relates to a method of treating a disease or IF-2019-16742483-APN-ANP#INPI 96 Page 96 of 402 STING-mediated disorder comprising administering a therapeutically effective amount of a compound of the present invention to a human being in need thereof. In another embodiment, the invention relates to a method of treating a STING-mediated disease or disorder comprising administering a therapeutically effective amount of a compound of formula (l-N), (I) or (l-P) or a salt, in particular a pharmaceutically acceptable salt thereof, to a human being in need. In another embodiment, the invention relates to a method of treating or preventing diseases comprising administering to a human subject suffering from or susceptible to a disease, an immunogenic composition comprising an antigen or an antigenic composition and a compound of formula ( l-N), (l-P) or (I), or a pharmaceutically acceptable salt thereof. In another embodiment, the invention relates to a method of treating or preventing diseases comprising administering to a human patient suffering from or susceptible to a disease, a vaccine composition comprising an antigen or an antigenic composition and a compound of formula (l-N), (l-P) or (I), or a pharmaceutically acceptable salt thereof. In one embodiment, the present invention relates to a compound of formula (l-N), (l-P) or (I), or a pharmaceutically acceptable salt thereof for use in the treatment of inflammation. In a further aspect, there is provided a method of treating inflammation comprising administering to a human in need thereof a therapeutically effective amount of a compound of formula (1-N), (1-P) or (I), or a pharmaceutically acceptable salt of the same. In a further aspect, there is provided a compound of formula (l-N), (l-P) or (I) or a pharmaceutically acceptable salt thereof for use in the manufacture of a medicament for the treatment of inflammation. In one embodiment, the present invention relates to a compound of formula (l-N), (l-P) or (I) or a pharmaceutically acceptable salt thereof for use in the treatment of an allergic disease. In a further aspect, there is provided a method of treating an allergic disease comprising administering to a human in need thereof a therapeutically effective amount of a compound of formula (1-N), (1-P) or (I) or a pharmaceutically acceptable salt of the same. In a further aspect, there is provided a compound of formula (l-N), (l-P) or (I) or a pharmaceutically acceptable salt thereof for use in the manufacture of a medicament for the treatment of an allergic disease. In one embodiment, the present invention relates to a compound of formula (l-N), (l-P) or (I) or a pharmaceutically acceptable salt thereof for use in the treatment of an autoimmune disease. In a further aspect, there is provided a method of treating an autoimmune disease comprising administering to a human in need thereof a therapeutically effective amount of a compound of formula (l-N), (l-P) or (I) or IF-2019-16742483-APN-ANP#INPI 97 Page 97 of 402 a pharmaceutically acceptable salt thereof. In a further aspect, there is provided a compound of formula (I-N), (I-P) or (I) or a pharmaceutically acceptable salt thereof for use in the manufacture of a medicament for the treatment of an autoimmune disease. In one embodiment, the present invention relates to a compound of formula (I-N), (I-P) or (I) or a pharmaceutically acceptable salt thereof for use in the treatment of an infectious disease. In a further aspect, there is provided a method of treating an infectious disease comprising administering to a human in need thereof a therapeutically effective amount of a compound of formula (I-N), (I-P) or (I) or a pharmaceutically acceptable salt of the same. In a further aspect, there is provided a compound of formula (I-N), (I-P) or (I) or a pharmaceutically acceptable salt thereof for use in the manufacture of a medicament for the treatment of an infectious disease. In one embodiment, the present invention relates to a method of treating an HIV infection in a human by administering to the human a therapeutically effective amount of a compound of formula (I-N), (I-P) or (I), or a pharmaceutically acceptable salt thereof. In one embodiment, the present invention relates to a method of treating an HIV infection, in a human being who has or is at risk of having the infection by administering to the human a therapeutically effective amount of a compound of formula (I-N), (I-P) or (I), or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to a method of treating an AIDS-causing infection in a human being at risk of having the infection by administering to the human a therapeutically effective amount of a compound of formula (I-N ), (I-P) or (I), or a pharmaceutically acceptable salt thereof. In one embodiment, the present invention relates to a method of treating an HBV infection in a human by administering to the human a therapeutically effective amount of a compound of formula (I-N), (I-P) or (I), or a pharmaceutically acceptable salt thereof. In one embodiment, the present invention relates to a method of treating an HBV infection, in a human being who has or is at risk of having the infection by administering to the human a therapeutically effective amount of a compound of formula (I-N), (I-P) or (I), or a pharmaceutically acceptable salt thereof. In one embodiment, the present invention relates to a method of treating an HCV infection in a human by administering to the human a therapeutically effective amount of a compound of formula (I-N), (I-P) or (I), or a pharmaceutically acceptable salt thereof. In one embodiment, the present invention relates to a method of treating an HCV infection in a human being. IF-2019-16742483-APN-ANP#INPI98 Page 98 of 402 has or is at risk of having the infection by administering to the human being a therapeutically effective amount of a compound of formula (l-N), (l-P) or (I), or a pharmaceutically acceptable salt thereof. In one embodiment, the present invention relates to a method of treating influenza in a human by administering to the human a therapeutically effective amount of a compound of formula (l-N), (l-P) or (I), or a pharmaceutically acceptable salt thereof. In one embodiment, the present invention relates to a method of treating influenza, in a human being who has or is at risk of having the infection by administering to the human a therapeutically effective amount of a compound of formula (l-N ), (l-P) or (I), or a pharmaceutically acceptable salt thereof. In one embodiment, the present invention relates to a method of treating a human papillomavirus (HPV) infection in a human by administering to the human a therapeutically effective amount of a compound of formula (l-N), (l-P) or (I), or a pharmaceutically acceptable salt thereof. In one embodiment, the present invention relates to a method of treating an HPV infection, in a human being who has or is at risk of having the infection by administering to the human a therapeutically effective amount of a compound of formula (l-N), (l-P) or (I), or a pharmaceutically acceptable salt thereof. As used herein, the terms cancer, neoplasia and tumor are used interchangeably and, whether in singular or plural form, refer to cells that have undergone a malignant transformation that renders them pathological for the organism. host. Primary cancer cells can be easily distinguished from non-cancerous cells by well-established techniques, particularly histological examination. The definition of a cancer cell, as used herein, includes not only a primary cancer cell, but any cell derived from an ancestor of the cancer cell. This includes metastasized cancer cells, and in vitro cultures and cell lines derived from cancer cells. When referring to a type of cancer that typically manifests as a solid tumor, a clinically detectable tumor is one that is detectable based on tumor mass; for example, by procedures such as computed tomography (CT) scanning, magnetic resonance imaging (MRI), cancer-specific antigens in a sample obtainable from a patient. The tumors may be a hematopoietic (or hematological or blood-related) cancer, for example, cancers arising from blood cells or immune cells, which may be referred to as liquid tumors. Specific examples of clinical conditions based on hematological tumors include leukemias, such as leukemia IF-2019-16742483-APN-ANP#INPI 99 Page 99 of 402 chronic myelocytic leukemia, acute myelocytic leukemia, chronic lymphocytic leukemia and acute lymphocytic leukemia; plasma cell malignancies, such as multiple myeloma, MGUS, and Waldenstrom's macroglobulinemia; lymphomas, such as non-Hodgkin lymphoma, Hodgkin lymphoma; and the like. Cancer can be any cancer in which an abnormal number of blast cells or unwanted cell proliferation is present or has been diagnosed as hematological cancer, including both lymphoid and myeloid malignancies. Myeloid malignancies include, but are not limited to, acute myeloid (or myelocytic or myelogenous or myeloblastic) leukemia (differentiated or undifferentiated), acute promyeloid (or promyelocytic or promyelogenic or promyeloblastic) leukemia, acute myelomonocytic (or myelomonoblastic) leukemia, monocytic leukemia. (or monoblastic), erythroleukemia and megakaryocytic (or megakaryoblastic) leukemia. These leukemias can be referred to together as acute myeloid (or myelocytic or myelogenous) leukemia (AML). Myeloid malignancies also include myeloproliferative disorders (MPD) including, but not limited to, chronic myelogenous (or myeloid) leukemia (CML), chronic myelomonocytic leukemia (CMML), essential thrombocythemia (or thrombocytosis), and polycythemia vera (PCV). Myeloid malignancies also include myelodysplasia (or myelodysplastic syndrome or MDS), which can be cited as refractory anemia (RA), refractory anemia with excess blasts (RAEB), and refractory anemia with excess blasts in transformation (RAEBT); as well as myelofibrosis (MFS) with or without agnogenic myeloid metaplasia. Hematopoietic cancers also include lymphoid malignancies, which can affect the lymph nodes, spleen, bone marrow, peripheral blood, and / or extranodal sites. Lymphoid cancers include B-cell malignancies, including, but not limited to, B-cell non-Hodgkin lymphomas (B-NHL). B-NHLs can be indolent (or low grade), intermediate grade (or aggressive), or high grade (very aggressive). Indolent B-cell lymphomas include follicular lymphoma (FL); small lymphocytic leukemia (SLL); marginal zone lymphoma (MZL), including nodal MZL, extranodal MZL, splenic MZL, and splenic MZL with villous lymphocytes; lymphoplasmacytic lymphoma (LPL); and mucosa-associated lymphoid tissue lymphoma (MALT or extranodal marginal zone). Intermediate-grade B-NHL includes mantle cell lymphoma (MCL) with or without leukemic involvement, diffuse large cell lymphoma (DLBCL), follicular large cell lymphoma (either grade 3 or grade 3B), and mediastinal lymphoma primary (PML). High-grade B-NHLs include Burkitt lymphoma (BL), Burkitt-type lymphoma, small uncleaved cell lymphoma (SNCCL), and lymphoblastic lymphoma. Other B-NHL include immunoblastic lymphoma (or immunocytoma), primary effusion lymphoma, HIV-associated (or AIDS-related) lymphomas, and disorder or lymphoma IF-2019-16742483 -APN-ANP#INPI100 Page 100 of 402 post-transplant lymphoproliferative disease (PTLD). B cell neoplasms also include, but are not limited to, chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), Waldenstrom macroglobulinemia (WM), tricholeukemia (HCL), large granular lymphocyte leukemia (LGL), lymphoid leukemia (or acute lymphocytic or lymphoblastic), and Castleman disease. NHL may also include T-cell non-Hodgkin lymphoma (T-NHL), including, but not limited to, T-cell non-Hodgkin lymphoma not otherwise specified (NOS), peripheral T-cell lymphoma (PTCL), anaplastic lymphoma large cell lymphoma (ALCL), angioimmunoblastic lymphoid disorder (AILD), nasal natural killer lymphocyte / T cell lymphoma, gamma / delta lymphoma, cutaneous T cell lymphoma, mycosis fungoides, and Sezary syndrome. Hematopoietic cancers also include Hodgkin lymphoma (or disease), including classical Hodgkin lymphoma, nodular sclerosing Hodgkin lymphoma, mixed cellularity Hodgkin lymphoma, lymphocyte predominant (LP) Hodgkin lymphoma, nodular LP Hodgkin lymphoma, and lymphoma Hodgkin's without lymphocytes. Hematopoietic cancers also include plasma cell diseases or cancers, such as multiple myeloma (MM) including smoldering MM, monoclonal gammopathy of undetermined (or unknown or unclear) significance (MGUS), plasmacytoma (bone, extramedullary), lymphoplasmacytic lymphoma (LPL), Waldenstrom macroglobulinemia, plasma cell leukemia, and primary amyloidosis (AL). Hematopoietic cancers may also include other cancers of additional hematopoietic cells, including polymorphonuclear leukocytes (or neutrophils), basophils, eosinophils, dendritic cells, platelets, erythrocytes, and natural killer lymphocytes. Tissues including hematopoietic cells referred to herein as hematopoietic cell tissues include bone marrow; peripherally blood; thymus; and peripheral lymphoid tissues, such as the spleen, lymph nodes, lymphoid tissues associated with the mucosa (such as lymphoid tissues associated with the intestine), tonsils, Peyer's patches and appendix, and lymphoid tissues associated with other mucosa, e.g. the bronchial linings. In one embodiment, the present invention relates to a compound of formula (I-N), (I-P) or (I) or a pharmaceutically acceptable salt thereof for use in the treatment of cancer and precancerous syndromes. In a further aspect there is provided a method of treating cancer and precancerous syndromes comprising administering to a human being in need thereof a therapeutically effective amount of a compound of formula (I-N), (I-P) or (I) or a pharmaceutically acceptable salt of the same. In a further aspect, there is provided a compound of formula (I-N), (I-P) or (I) or a pharmaceutically acceptable salt thereof for use in the manufacture of a medicament for the treatment of cancer and precancerous syndromes. Associated autoimmune diseases include, but are not limited to, vasculitis IF-2019-16742483-APN-ANP#INPI101 Page 101 of 402 associated with STING with onset in childhood (SAVI), Aicardi Goutieres syndrome (AGS), chilblain lupus, ataxia telangectasia (also referred to as Louis-Bar syndrome), retinal vasculopathy with cerebral leukodystrophy (RCVL), lupus systemic erythematosus (SLE), cutaneous lupus, lupus nephritis, psoriasis, diabetes mellitus, including insulin-dependent diabetes mellitus (IDDM), dermatomyositis, human immunodeficiency virus (HIV), AIDS, polymyositis, systemic sclerosis (scleroderma), and Sjogren's syndrome (SS), rheumatoid arthritis, psoriatic arthritis, polyarthritis, myasthenia gravis, polyarteritis nodosa, vasculitis, cutaneous vasculitis, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, Henoch-Schonlein purpura, autoimmune hepatitis, primary sclerosing cholangitis, Wegener's granulomatosis, microscopic polyangiitis, Behcet's disease, spondylitis, giant cell arteritis, polymyalgia rheumatica, Raynaud's phenomenon, primary biliary cirrhosis, primary angiitis of microscopic polyangiitis of the central nervous system, neuromyelitis optica, and mixed connective tissue disease. Inflammation represents a group of vascular, cellular and neurological responses to trauma. Inflammation can be characterized as the movement of inflammatory cells, such as monocytes, neutrophils, and granulocytes into tissues. This is usually associated with reduced endothelial barrier function and edema in the tissues. Inflammation can be classified as acute or chronic. Acute inflammation is the body's initial response to harmful stimuli and is achieved by the increased movement of plasma and leukocytes from the blood to injured tissues. A cascade of biochemical events propagates and matures the inflammatory response, involving the local vascular system, the immune system, and various cells in the injured tissue. Prolonged inflammation, known as chronic inflammation, results in a progressive change in the type of cells that are present at the site of inflammation and is characterized by the simultaneous destruction and healing of tissue due to the inflammatory process. When it occurs as part of an immune response to infection or as an acute response to trauma, inflammation can be beneficial and is usually self-limiting. However, inflammation can be harmful in several conditions. This includes the production of excessive inflammation in response to infectious agents, which can lead to significant organ damage and death (for example, in a situation of septicemia). Furthermore, chronic inflammation is generally harmful and is at the root of numerous chronic diseases, causing serious and irreversible damage to tissues. In such situations, the immune response is often directed against one's own tissues (autoimmunity), although chronic responses to exogenous entities may also result in accompanying damage to one's tissues. The goal of anti-inflammatory therapy is therefore to reduce this inflammation, IF-2019-16742483-APN-ANP#INPI102 Page 102 of 402 inhibit autoimmunity when it is present, and allow the physiological process of healing and tissue repair to advance. The compounds of the present invention can be used to treat inflammation of any tissue and organs of the body, including musculoskeletal inflammation, vascular inflammation, neural inflammation, inflammation of the digestive system, ocular inflammation, inflammation of the reproductive system, and other inflammation, such as is exemplified later. Musculoskeletal inflammation refers to any inflammatory condition of the musculoskeletal system, particularly those conditions affecting the skeletal joints, including the joints of the hand, wrist, elbow, shoulder, jaw, spine, neck, hip, knee, ankle, and foot, and conditions that affect tissues that connect muscles to bones, such as tendons. Examples of musculoskeletal inflammation that can be treated with compounds of the invention include arthritis (including, for example, osteoarthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, acute and chronic infectious arthritis, arthritis associated with gout and pseudogout, and juvenile idiopathic arthritis). , tendonitis, synovitis, tenosynovitis, bursitis, fibrositis (fibromyalgia), epicondylitis, myositis, and osteitis (including, for example, Paget's disease, osteitis pubis, and osteitis cystica fibrosa). Ocular inflammation refers to inflammation of any structure of the eye, including the eyelids. Examples of ocular inflammation that can be treated with the compounds of the invention include blepharitis, blepharochalasis, conjunctivitis, dacryoadenitis, keratitis, keratoconjunctivitis sicca (dry eye), scleritis, trichiasis, and uveitis. Examples of inflammation of the central nervous system that can be treated with the compounds of the invention include encephalitis, Guillain-Barre syndrome, meningitis, neuromyotonia, narcolepsy, multiple sclerosis, myelitis, CNS vasculitis, and schizophrenia. Examples of inflammation of the vasculature or lymphatic system that can be treated with the compounds of the invention include arthrosclerosis, arthritis, phlebitis, vasculitis, and lymphangitis. Examples of inflammatory conditions of the digestive system that can be treated with the compounds of the invention include cholangitis, choleocystitis, enteritis, enterocolitis, gastritis, gastroenteritis, inflammatory bowel disease (such as Crohn's disease and ulcerative colitis), ileitis, and proctitis. Examples of inflammatory conditions of the reproductive system that can be treated with the compounds of the invention include cervicitis, chorioamnionitis, endometritis, epididymitis, omphalitis, oophoritis, orchitis, salpingitis, tube-ovarian abscesses, urethritis, vaginitis, vulvitis, and vulvodynia. The compounds of the present invention can be used to treat conditions IF-2019-16742483-APN-ANP#INPI103 Page 103 of 402 autoimmune diseases that have an inflammatory component. Such conditions include acute universalized disseminated alopecia, Behcet's disease, Chagas' disease, STING-associated vasculitis with onset in infancy (SAVI), Aicardi Goutieres syndrome (AGS), chilblain lupus, ataxia telangiectasia (also referred to as Louis syndrome). Bar), retinal vasculopathy with cerebral leukodystrophy (RCVL), ANCA-associated vasculitis, chronic fatigue syndrome, dysautonomia, encephalomyelitis, ankylosing spondylitis, aplastic anemia, hidradenitis suppurativa, autoimmune hepatitis, autoimmune oophoritis, celiac disease, Crohn's disease, diabetes mellitus type I, giant cell arteritis, Goodpasture syndrome, Grave's disease, Guillain-Barre syndrome, Hashimoto's disease, Henoch-Schonlein purpura, Kawasaki disease, lupus erythematosus, microscopic colitis, microscopic polyarteritis, tissue disease mixed connective tissue, multiple sclerosis, myasthenia gravis, opsoclonus myoclonus syndrome, optic neuritis, ord thyroiditis, pemphigus, polyarteritis nodosa, polymyalgia, rheumatoid arthritis, Reiter's syndrome, Sjogren's syndrome, temporal arteritis, Wegener's granulomatosis, warm autoimmune hemolytic anemia , interstitial cystitis, Lyme disease, morphea, psoriasis, sarcoidosis, scleroderma, ulcerative colitis, and vitiligo. The compounds of the present invention can be used to treat T cell-mediated hypersensitivity diseases that have an inflammatory component. Such conditions include contact hypersensitivity, contact dermatitis (including that due to poison ivy), hives, skin allergies, respiratory allergies (hay fever, allergic rhinitis), and gluten-sensitive enteropathy (celiac disease). Other inflammatory conditions that can be treated with the compounds of the present invention include, for example, appendicitis, dermatitis, dermatomyositis, endocarditis, fibrositis, gingivitis, glossitis, hepatitis, hidradenitis suppurativa, iritis, laryngitis, mastitis, myocarditis, nephritis, otitis, pancreatitis , parotitis, pericarditis, peritonitis, pharyngitis, pleuritis, pneumonitis, prostatitis, pyelonephritis, and stomatitis, transplant rejection (involving organs, such as kidney, liver, heart, lung, pancreas (e.g., islet cells), marrow bone, cornea, small intestine, skin allografts, skin homografts, and heart valve xenografts, serum sickness, and graft versus host disease), acute pancreatitis, chronic pancreatitis, respiratory distress syndrome, Sezary syndrome, congenital adrenal hyperplasia, non-suppurative thyroiditis, hypercalcemia associated with cancer, pemphigus, bullous dermatitis herpetiformis, severe erythema multiforme, exfoliative dermatitis, seborrheic dermatitis, seasonal or perennial allergic rhinitis, bronchial asthma, contact dermatitis, atopic dermatitis, hypersensitivity reactions to drugs, allergic conjunctivitis, keratitis, herpes zoster ophthalmicus, iritis and iridocyclitis, chorioretinitis, optic neuritis, symptomatic sarcoidosis, fulminant or disseminated pulmonary tuberculosis, chemotherapy, purpura IF-2019-16742483-APN-ANP#INPI104 Page 104 of 402 idiopathic thrombocytopenia in adults, secondary thrombocytopenia in adults, acquired hemolytic (autoimmune) anemia, leukemia and lymphomas in adults, acute leukemia of childhood, regional enteritis, autoimmune vasculitis, multiple sclerosis, chronic obstructive pulmonary disease, transplant rejection of solid organs, sepsis. Preferred treatments include treatment of transplant rejection, rheumatoid arthritis, psoriatic arthritis, multiple sclerosis, type 1 diabetes, asthma, inflammatory bowel disease, systemic lupus erythematosus, psoriasis, chronic lung disease, and inflammation accompanying infectious diseases ( for example, sepsis). In one embodiment, the compounds of the present invention can be used to treat asthma. Examples of diseases and cancer conditions in which a compound of the present invention may have potentially beneficial antitumor effects include, but are not limited to, cancers of the lung, bone, pancreas, skin, head, neck, uterus, ovaries, stomach, colon, breast, esophagus, small intestine, intestine, endocrine system, thyroid gland, parathyroid gland, adrenal gland, urethra, prostate, penis, testicles, ureter, bladder, kidney or liver; rectal cancer; cancer of the anal region; carcinomas of the fallopian tube, endometrium, cervix, vagina, vulva, renal pelvis, renal cells; soft tissue sarcoma; myxoma; rhabdomyoma; fibroma; lipoma; teratoma; cholangiocarcinoma; hepatoblastoma; angiosarcoma; hemangioma; hepatoma; fibrosarcoma; chondrosarcoma; myeloma; chronic or acute leukemia; lymphocytic lymphomas; primary CNS lymphoma; CNS neoplasms; spinal axis tumors; squamous cell carcinomas; synovial sarcoma; malignant pleural mesotheliomas; brain stem glioma; pituitary adenoma; bronchial adenoma; chondromatous hamartoma; mesothelioma; Hodgkin's disease or a combination of one or more of the above cancers. Suitably, the present invention relates to a method for treating or alleviating the severity of cancers selected from the group consisting of brain cancer (gliomas), glioblastomas, astrocytomas, glioblastoma multiforme, BannayanZonana syndrome, Cowden disease, Lhermitte-Duclos tumor, Wilm tumor, Ewing sarcoma, rhabdomyosarcoma, ependymoma, medulloblastoma, head and neck, kidney, liver, melanoma, ovarian, pancreatic, adenocarcinoma, ductal carcinoma, adenosquamous carcinoma, acinar cell carcinoma, glucagonoma, insulinoma , prostate, sarcoma, osteosarcoma, giant cell tumor of bone, thyroid, T-cell lymphoblastic leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, tricholeukemia, acute lymphoblastic leukemia, acute myelogenous leukemia, chronic neutrophilic leukemia, acute T-cell lymphoblastic leukemia , plasmacytoma, immunoblastic large cell leukemia, mantle cell leukemia, multiple myeloma, megakaryoblastic leukemia, multiple myeloma, acute megakaryocytic leukemia, promyelocytic leukemia, erythroleukemia, malignant lymphoma, lymphoma IF-2019-16742483-APN-ANP#INPI 1θ5 Page 105 of 402 Hodgkin, non-Hodgkin lymphoma, T-cell lymphoblastic lymphoma, Burkitt lymphoma, follicular lymphoma, neuroblastoma, bladder cancer, urothelial cancer, vulvar cancer, cervical cancer, endometrial cancer, kidney cancer, mesothelioma, esophageal cancer, salivary gland cancer, hepatocellular cancer, gastric cancer, nasopharyngeal cancer, oral cancer, mouth cancer, GIST (gastrointestinal stromal tumor) and testicular cancer. In some embodiments, the compounds of the present invention can be used to treat solid or liquid tumors. In some embodiments, the compounds of the present invention can be used to treat sarcoma, breast cancer, colorectal cancer, gastroesophageal cancer, melanoma, non-small cell lung cancer (NSCLC), clear cell renal cell carcinoma (RCC), lymphomas, squamous cell carcinoma of the head and neck (SCCHN), hepatocellular carcinoma (HCC), and / or non-Hodgkin lymphoma (NHL). Suitably, the present invention relates to a method for treating or alleviating the severity of precancerous syndromes in a mammal, including a human, wherein the precancerous syndrome is selected from: cervical intraepithelial neoplasia, monoclonal gammopathy of significance unknown (MGUS), myelodysplastic syndrome, aplastic anemia, cervical lesions, cutaneous nevi (pre-melanoma), prosthetic (intraductal) intraepithelial neoplasia (PIN), ductal carcinoma in situ (DCIS), colon polyps and severe hepatitis or cirrhosis. In one aspect, the human being has a solid tumor. In one aspect, the tumor is selected from head and neck cancer, gastric cancer, melanoma, renal cell carcinoma (RCC), esophageal cancer, non-small cell lung carcinoma, prostate cancer, colorectal cancer, ovarian cancer and cancer. pancreatic. In one aspect, the human has one or more of the following: colorectal cancer (CRC), esophageal, cervical, bladder, breast, head and neck, ovarian, melanoma, renal cell carcinoma (RCC), CD squamous cell carcinoma, non-small cell lung carcinoma, mesothelioma, and prostate cancer. In another aspect, human has a liquid tumor, such as diffuse large B cell lymphoma (DLBCL), multiple myeloma, chronic lymphocytic leukemia (CLL), follicular lymphoma, acute myeloid leukemia and chronic myelogenous leukemia. In one embodiment, the compounds of the present invention may be useful for the treatment of skin cancers (e.g., non-melanoma skin cancer, squamous cell carcinoma, basal cell carcinoma) or actinic keratosis. In addition to a field effect in eliminating superficial skin cancers, the compounds of the present invention can prevent the development of subsequent skin cancers and premalignant actinic keratoses in treated patients. The compounds of the present invention may also be useful in the treatment of one or more diseases affecting mammals that are characterized by proliferation IF-2019-16742483 -APN-ANP#INPI106 Page 106 of 402 cellular in the area of ​​disorders associated with neovascularization and / or vascular permeability, including proliferative disorders of blood vessels, including arthritis (rheumatoid arthritis) and restenosis; fibrotic disorders, including liver cirrhosis and atherosclerosis; mesangial cell proliferative disorders include glomerulonephritis, diabetic nephropathy, diabetic nephrosclerosis, thrombotic microangiopathic syndromes, proliferative retinopathies, organ transplant rejection, and glomerulopathies; and metabolic disorders include psoriasis, diabetes mellitus, chronic wound healing, inflammation, and neurodegenerative diseases. The compounds of the present invention can be used to treat neurodegenerative diseases. Exemplary neurodegenerative diseases include, but are not limited to, multiple sclerosis, Huntington's disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS). The compounds of the present invention can be used to treat an infectious disease, which is any disease instigated or coincident with an infection due to a pathogen. Pathogens are broadly defined as any species of organism that is exogenous to a human tissue environment. Common disease-causing pathogens include bacteria (many such as TB), viruses (many such as HBV, HIV, influenza), and parasitic protozoa (such as P. falciparum which causes malaria). The compounds of the present invention can be used to treat infectious diseases caused by bacteria, such as TB infection {Mycobacterium tuberculosis), chlamydia, tularemia infection {Francisella tularensis), plasmodium infection or DNA or RNA virus infections. The compounds of the present invention can be used to treat infectious diseases caused by the DNA virus families: Herpesviridae (herpes simplex virus1, Kaposi sarcoma-associated virus and Epstein-Barr virus), PapiHomaviridae (human papillomavirus), adenovirus and Hepadnaviridae (hepatitis B virus). Examples of RNA virus families include Retroviridiae (human immunodeficiency virus), Flaviviridae (dengue virus, hepatitis C virus), Orthomyxoviridae (influenza), and Coronaviridae (human coronavirus and SARS coronzovirus). The compounds of the present invention can be used alone or in combination with other therapeutic agents. As modulators of the immune response, the compounds of the present invention can also be used in monotherapy or used in combination with another therapeutic agent in the treatment of diseases and conditions in which the modulation of STING is beneficial. Combination therapies according to the present invention therefore comprise the administration of a compound of formula (IN), (1-P) or (I) or a pharmaceutically acceptable salt thereof, and at least one other different therapeutically active agent. In one embodiment, the combined therapies according to IF-2019-16742483-APN-ANP#INPI107 Page 107 of 402 The present invention comprises the administration of at least one compound of formula (IN), (1-P) or (I) or a pharmaceutically acceptable salt thereof, and at least one different therapeutic agent. The compounds of formula (l-N), (l-P) or (I) and the pharmaceutically acceptable salts thereof, and the other therapeutic agents may be administered together in a single pharmaceutical composition or separately and, when administered separately, this may happen simultaneously or sequentially in any order. The amounts of the compounds of formula (l-N), (l-P) or (I) and the pharmaceutically acceptable salts thereof, and the other therapeutic agents and the relative times of administration will be selected to achieve the desired combined therapeutic effect. Therefore, in a further aspect, there is provided a combination comprising a compound of formula (1-N), (1-P) or (I), or a pharmaceutically acceptable salt thereof, together with one or more different therapeutic agents. The compounds of formula (l-N), (l-P) or (I) and pharmaceutically acceptable salts thereof can be used in combination with one or more different therapeutic agents that may be useful in the prevention or treatment of allergic diseases, inflammatory diseases, or autoimmune diseases, for example, immunotherapy with antigens, antihistamines, steroids, NSAIDs, bronchodilators (for example, beta 2 agonists, adrenergic agonists, anticholinergic agents, theophylline), methotrexate, leukotriene modulators and similar agents; therapy with monoclonal antibodies, such as anti-IgE, anti-TNF, anti-IL-5, anti-IL-6, anti-IL-12, anti-IL-1 and similar agents; receptor therapies, for example, etanercept and similar agents; non-antigen-specific immunotherapies (for example, interferon or other cytokines / chemokines, cytokine / chemokine receptor modulators, cytokine agonists or antagonists, TLR agonists, and similar agents). The compounds of formula (l-N), (l-P) or (I) and pharmaceutically acceptable salts thereof can be used in combination with radiotherapy and / or surgery and / or at least one other therapeutic agent that may be useful in the treatment of cancer and precancerous syndromes. Any antineoplastic agent that has activity against a susceptible tumor being treated can be used in the combination. Typical useful antineoplastic agents include, but are not limited to, antimicrotubule agents, such as diterpenoids and vinca alkaloids; platinum coordination complexes; alkylating agents, such as nitrogen mustards, oxaazaphosphorines, alkylsulfonates, nitrosoureas, and triazenes; antibiotic agents, such as anthracyclines, actinomycins and bleomycins; topoisomerase II inhibitors, such as epipodophyllotoxins; antimetabolites, such as purine and pyrimidine analogues and antifolate compounds; topoisomerase I inhibitors, such as camptothecins; hormones and hormonal analogues; transduction pathway inhibitors IF-2019-16742483 -APN-ANP#INPll 08 Page 108 of 402 signs; non-tyrosine receptor angiogenesis inhibitors; immunotherapeutic agents; proapoptotic agents; cell cycle signaling inhibitors; immuno-oncology agents and immunostimulatory agents. Anti-microtubule agents or antimitotic agents are phase-specific agents active against the microtubules of tumor cells during the M or mitosis phase of the cell cycle. Examples of anti-microtubule agents include, but are not limited to, diterpenoids and vinca alkaloids. Diterpenoids, which come from natural sources, are phase-specific anti-cancer agents that function in the G2 / M phases of the cell cycle. Diterpenoids are believed to stabilize the β-tubulin subunit of microtubules by binding to this protein. The disassembly of the protein appears to be inhibited, stopping mitosis and causing cell death. Examples of diterpenoids include, but are not limited to, paclitaxel and its analog, docetaxel. Paclitaxel, 4,10-diacetate 2-benzoate 13-ester 5β,20-βροχί-1,2α,4,7β,10β,13αhexa-hydroxytax-ll-en-9-one with (2R,3S)-N -benzo¡l-3-phenyl¡sorserna; is a natural diterpene product isolated from the Pacific yew tree, Taxus brevifolia and is commercially available in the form of an injectable solution, TAXOL®. It is a member of the taxane family of terpenes. Paclitaxel has been approved for clinical use in the treatment of refractory ovarian cancer in the United States (Markman et al., Yale Journal of Biology and Medicine, 64:583, 1991; McGuire et al., Ann. Intern, Med ., 111:273, 1989) and for the treatment of breast cancer (Holmes et al., 1 Nat. Cancer Inst., 83:1797, 1991). It is a potential candidate for the treatment of skin neoplasms (Einzig et. al., Proc. Am. Soc. Clin. Oncol., 20:46) and head and neck carcinomas (Forastire et. al., Sem. Oncol., 20:56, 1990). The compound also shows potential for the treatment of polycystic kidney disease (Woo et al., Nature, 368:750. 1994), lung cancer and malaria. Treatment of patients with paclitaxel results in bone marrow suppression (multiple cell lineages, Ignoff, RJ. et. al, Cancer Chemotherapy Pocket Guide£1998) related to the duration of dosing above a threshold concentration (50 nM) (Kearns, C.M. et. al., Seminars in Oncology, 3(6) p. 16-23, 1995). Docetaxel, N-butyl ester, 13-(2R,3S)-N-carboxy-3-phenysoserine ester with 5β-20-θροχΙ-1,2α,4,7β 4-acetate trihydrate ,10β,13α-ίΊ6Χ3ΐ'ί^Γθχίί3χ-11-θη-9ona; It is commercially available in the form of an injectable solution as TAXOTERE0. Docetaxel is indicated for the treatment of breast cancer. Docetaxel is a semisynthetic derivative of paclitaxel q.v., prepared using a natural precursor, 10-desacetyl-baccatin III, extracted from the needle of the European yew tree. Vinca alkaloids are phase-specific antineoplastic agents derived from IF-2019-16742483-APN-ANP#INPll09 Page 109 of 402 the periwinkle plant. Vinca alkaloids act in the M phase (mitosis) of the cell cycle by binding specifically to tubulin. Consequently, the bound tubulin molecule is unable to polymerize into microtubules. Mitosis is thought to stop at metaphase and cell death follows. Examples of vinca alkaloids include, but are not limited to, vinblastine, vincristine, and vinorelbine. Vinblastine, vincaleucoblastine sulfate, is commercially available as VELBAN® in the form of an injectable solution. Although it has a possible indication as a second-line treatment for several solid tumors, it is mainly indicated in the treatment of testicular cancer and several lymphomas, including Hodgkin's disease; and lymphocytic and histiocytic lymphomas. Myelosuppression is the dose-limiting side effect of vinblastine. Vincristine, vincaleucoblastine 22-oxo-sulfate, is commercially available as ONCOVIN® in the form of an injectable solution. Vincristine is indicated for the treatment of acute leukemias and has also proven useful in treatment regimens for malignant Hodgkin and non-Hodgkin lymphomas. Alopecia and neurological effects are the most common side effect of vincristine, and to a lesser extent, myelosuppression and gastrointestinal mucositis occur. Vinorelbine, 3',4'-didehydro-4'-deoxy-C'-norvincaleucoblastin [R-(R*,R*)-2,3dihydroxybutanedioate (l:2)(salt)], is commercially available as a vinorelbine tartrate injection solution (NAVELBINE®), is a semisynthetic vinca alkaloid. Vinorelbine is indicated for use as a single agent or in combination with other chemotherapeutic agents, such as cisplatin, in the treatment of various solid tumors, particularly non-small cell lung, advanced breast, and hormone-refractory prostate cancers. Myelosuppression is the most common dose-limiting side effect of vinorelbine. Platinum coordination complexes are non-phase-specific anticancer agents that interact with DNA. Platinum complexes enter tumor cells, undergo hydration and form intra- and interchain cross-links with DNA, causing adverse biological effects to the tumor. Examples of platinum coordination complexes include, but are not limited to, oxaliplatin, cisplatin and carboplatin. Cisplatin, cis-diaminodichloroplatinum, is available commercially as PLATINOL® in the form of an injectable solution. Cisplatin is primarily indicated for the treatment of metastatic testicular and ovarian cancer and advanced bladder cancer. Carboplatin, platinum diamine [l,l-cyclobutane-dicarboxylate(2-)-O,O'], is commercially available as PARAPLATIN® in the form of an injectable solution. Carboplatin is indicated mainly in the first and second line treatment of IF-2019-16742483-APN-ANP#INPI110 Page 110 of 402 advanced ovarian carcinoma. Alkylating agents are phase-nonspecific and strong electrophilic anticancer agents. Typically, alkylating agents form covalent bonds, by alkylation, with DNA through nucleophilic moieties of the DNA molecule, such as phosphate, amino, amino, hydroxy, carboxyl and imidazole groups. Said alkylation alters the function of the nucleic acid, leading to cell death. Examples of alkylating agents include, but are not limited to, nitrogen mustards, such as cyclophosphamide, melphalan, and chlorambucil; alkyl sulfonates, such as busulfan; nitrosoureas, such as carmustine; and triazenes, such as dacarbazine. Cyclophosphamide, 2-[bis(2-chloroethyl)amino]tetrahydro-2H1,3,2-oxaazaphosphorine 2-oxide monohydrate, is commercially available as an injectable solution or tablets as CYTOXAN®. Cyclophosphamide is indicated for use as a single agent or in combination with other chemotherapeutic agents, in the treatment of malignant lymphomas, multiple myeloma, and leukemias. Melphalan, 4-[bis(2-chloroethyl)amino]-L-phenylalanine, is commercially available as an injectable solution or tablets as ALKERAN®. Melphalan is indicated for the palliative treatment of multiple myeloma and unresectable epithelial carcinoma of the ovary. Bone marrow suppression is the most common dose-limiting side effect of melphalan. Chlorambucil, 4-[bis(2-chloroethyl)amino]benzenebutanoic acid, is commercially available as LEUKERAN® in tablets. Chlorambucil is indicated for the palliative treatment of chronic lymphatic leukemia, and malignant lymphomas, such as lymphosarcoma, giant follicular lymphoma, and Hodgkin's disease. Busulfan, 1,4-butanediol dimethanesulfonate, is commercially available as MYLERAN® in tablets. Busulfan is indicated for the palliative treatment of chronic myelogenous leukemia. Carmustine, l,3-[bis(2-chloroethyl)-l-nitrosourea, is commercially available in the form of individual vials of lyophilized material such as BiCNU®. Carmustine is indicated for palliative treatment as a single agent or in combination with other agents for brain tumors, multiple myeloma, Hodgkin's disease, and non-Hodgkin's lymphomas. Dacarbazine, 5-(3,3-dimethyl-l-traazene)-imidazole-4-carboxarnide, is commercially available in the form of individual vials of material such as DTIC-Dome°. Dacarbazine is indicated for the treatment of metastatic malignant melanoma and for use in combination with other agents for the second-line treatment of Hodgkin's disease. Antineoplastic antibiotics are non-phase-specific agents, which bind to or IF-2019-16742483-APN-ANP#INPI111 Page 111 of 402 intercalate with DNA. Typically, such action results in stable DNA complexes or strand breakage, which disrupts the normal function of nucleic acids, resulting in cell death. Examples of antineoplastic antibiotic agents include, but are not limited to, actinomycins, such as dactinomycin, anthracyclines, such as daunorubicin and doxorubicin; and blemocins. Dactinomycin, also known as actinomycin D, is commercially available in injectable form as COSMEGEN®. Dactinomycin is indicated for the treatment of Wilm's tumor and rhabdomyosarcoma. Daunorubicin, (8S-cis-)-8-acetyl-10-[(3-amino-2,3,6-trideoxy-a-Llixo-hexopyranosyl)oxy]-7,8,9,10-tetrahydrochloride -6,8,ll-trihydroxy-l-methoxy-5,12 naphthacenedione, is commercially available in injectable liposomal form as DAUNOXOME® or in injectable form as CERUBIDINE®. Daunorubicin is indicated to induce remission in the treatment of acute nonlymphocytic leukemia and advanced Kaposi's sarcoma associated with HIV. Doxorubicin, (8S,10S)-10-[(3-amino-2,3,6-tridesoxy¡-a-L-lixohexop¡ranos¡l)oxy]-8-glycoloyl hydrochloride,7,8,9,10 -tetrahydro-6,8,ll-trihydroxy-l-methoxy-5,12 naphthacenedione, is commercially available in injectable form as RUBEX® or ADRIAMYCIN RDF®. Doxorubicin is indicated primarily for the treatment of acute lymphoblastic leukemia and acute myeloblastic leukemia, but also a useful component in the treatment of some solid tumors and lymphomas. Bleomycin, a cytotoxic glycopeptide antibiotic mixture isolated from a strain of Streptomyces verticillus, is commercially available as BLENOXANE®. Bleomycin is indicated as palliative treatment, as a single agent or in combination with other agents, of squamous cell carcinoma, lymphomas, and testicular carcinomas. Topoisomerase II inhibitors include, but are not limited to, epipodophyllotoxins. Epipodophyllotoxins are phase-specific antineoplastic agents derived from the mandrake plant. Epipodophyllotoxins typically affect cells in the S and G2 phases of the cell cycle by forming a ternary complex with topoisomerase II and DNA causing DNA strand breaks. Strand breaks accumulate and cause cell death. Examples of epipodophyllotoxins include, but are not limited to, etoposide and teniposide. Etoposide, 4'-desmethylepipodophyllotoxin 9[4,6-0-(R)-ethylidene-p-D-glucopyranoside], is commercially available as an injectable solution or as capsules as VePESID® and is commonly known as VP. -16. Etoposide is indicated as a single agent or in combination with other chemotherapeutic agents in the treatment of testicular and non-small cell lung cancers. Teniposide, 4'-desmethylIF-2019-16742483-APN-ANP#INPI112 Page 112 of 402 epipodophyllotoxin, is commercially available in the form of an injectable solution as VUMON® and is commonly known as VM-26. Teniposide is indicated as a single agent or in combination with other chemotherapeutic agents in the treatment of acute leukemia in children. Antineoplastic metabolite agents are phase-specific antineoplastic agents that act in the S phase (DNA synthesis) of the cell cycle by inhibiting DNA synthesis or inhibiting the synthesis of purine or pyrimidine bases and thus limiting DNA synthesis. Consequently, the S phase does not continue and cell death occurs. Examples of antimetabolite antineoplastic agents include, but are not limited to, fluorouracil, methotrexate, cytarabine, mercaptopurine, thioguanine, and gemcitabine. 5-Fluorouracil, 5-fluoro-2,4-(1H,3H)pyrimidinedione, is commercially available as fluorouracil. Administration of 5-fluorouracil results in inhibition of thymidylate synthesis and is also incorporated into both RNA and DNA. The result is typically cell death. 5-Fluorouracil is indicated as a single agent or in combination with other chemotherapeutic agents in the treatment of carcinomas of the breast, colon, rectum, stomach and pancreas. Other fluoropyrimidine analogs include 5-fluorodeoxyuridine (floxuridine) and 5-fluorodeoxyuridine monophosphate. Cytarabine, 4-amino-l-p-D-arabinofuranosyl-2 (lH)-pyrimidinone, is commercially available as CYTOSAR-U® and is commonly known as Ara-C. Cytarabine is believed to display cell phase specificity in S phase by inhibiting DNA strand extension by terminal incorporation of cytarabine into the growing DNA strand. Cytarabine is indicated as a single agent or in combination with other chemotherapeutic agents in the treatment of acute leukemia. Other cytidine analogues include 5-azacytidine and 2',2'-difluorodeoxycytidine (gemcitabine). Mercaptopurine, l,7-dihydro-6H-purin-6-thione monohydrate, is commercially available as PURINETHOL®. Mercaptopurine shows cell phase specificity in the S phase by inhibiting DNA synthesis through a mechanism yet to be determined. Mercaptopurine is indicated as a single agent or in combination with other chemotherapeutic agents in the treatment of acute leukemia. A useful analogue of mercaptopurine is azathioprine. Thioguanine, 2-amino-1,7-dihydro-6H-purin-6-thione, is commercially available as TABLOID®. Thioguanine shows cell phase specificity in the S phase by inhibiting DNA synthesis through a mechanism yet to be determined. Thioguanine is indicated as a single agent or in combination with other chemotherapeutic agents in the treatment of acute leukemia. Other purine analogs include pentostatin, erythrohydroxynonyladenine (EHNA), fludarabine phosphate, and cladribine. IF-2019-16742483-APN-ANP#INPI113 Page 113 of 402 Gemcitabine, 2'-deoxy-2',2'-difluorocytidine monohydrochloride (β-isomer), is commercially available as GEMZAR®. Gemcitabine displays cell phase specificity in the S phase by blocking the progression of cells across the Gl / S boundary. Gemcitabine is indicated in combination with cisplatin in the treatment of locally advanced non-small cell lung cancer and alone in the treatment of locally advanced pancreatic cancer. Methotrexate, N-[4[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-Lglutamic acid, is commercially available as methotrexate sodium. Methotrexate shows effects on the cell phase specifically in the S phase by inhibiting DNA synthesis, repair and / or replication through the inhibition of dihydrofolic acid reductase which is necessary for the synthesis of purine nucleotides and thymidylate. Methotrexate is indicated as a single agent or in combination with other chemotherapeutic agents in the treatment of choriocarcinoma, meningeal leukemia, non-Hodgkin lymphoma, and carcinomas of the breast, head, neck, ovary, and bladder. Camptothecins, including camptothecin and camptothecin derivatives, are available or under development as topoisomerase I inhibitors. The cytotoxic activity of camptothecins is believed to be related to their topoisomerase I inhibitory activity. Examples of camptothecins include, but are not limited to, irinotecan, topotecan, and the various optical forms of 7-(4-methylpiperazino-methylene)-10,ll-ethylenediox¡-20-camptothecin described below. Irinotecan HCI, (4S)-4,ll-diethyl-4-hydroxy-9-[(4piperidinopiperidino)carbonyloxy]-lH-pyran[3',4',6,7]indolizino[l,2] hydrochloride -b]quinolin-3,14(4H,12H)dione, is commercially available in the form of the CAMPTOSAR® injectable solution. Irinotecan is a camptothecin derivative that binds, together with its active metabolite SN-38, to the topoisomerase I - DNA complex. Cytotoxicity is believed to occur as a result of irreparable double-strand breaks caused by the interaction of the ternary complex topoisomerase I:DNA:irinotecan or SN-38 with replication enzymes. Irinotecan is indicated for the treatment of metastatic cancer of the colon or rectum. Topotecan HCl, (S)-10-[(dimethylamino)methyl]-4-ethyl-4,9-dihydroxylH-pyran[3',4',6,7]indolizino monohydrochloride [l,2-b]quinolin-3,14-(4H,12H)-dione is commercially available in the form of HYCAMTIN® injectable solution. Topotecan is a camptothecin derivative that binds to the topoisomerase I-DNA complex and prevents the relegation of single-strand breaks caused by topoisomerase I in response to torsional stress of the DNA molecule. Topotecan is indicated as second-line treatment of metastatic ovarian carcinoma and small cell lung cancer. Hormones and hormone analogs are useful compounds for treating cancers in IF-2019-16742483-A PN-AN P#IN P414 Page 114 of 402 that there is a relationship between hormones and the growth and / or absence of cancer growth. Examples of hormones and hormonal analogs useful in the treatment of cancer include, but are not limited to, adrenocorticosteroids, such as prednisone and prednisolone, which are useful in the treatment of malignant lymphoma and acute leukemia in children, aminoglutethimide and other aromatase inhibitors. , such as anastrozole, letrozole, vorozole, and exemestane, useful in the treatment of adrenocortical carcinoma and hormone-dependent breast carcinoma containing estrogen receptors; progestins, such as megestrol acetate, useful in the treatment of hormone-dependent breast cancer and endometrial carcinoma; estrogens, and antiestrogens, such as fulvestrant, flutamide, nilutamide, bicalutamide, cyproterone acetate and 5a-reductases, such as finasteride and dutasteride, useful in the treatment of prostate carcinoma and benign prostatic hypertrophy; antiestrogens, such as tamoxifen, toremifene, raloxifene, droloxifene, iodoxifene, as well as selective estrogen receptor modulators (SERMS), such as those described in US Patent Nos. 5,681,835, 5,877,219, and 6,207,716, useful in the treatment of hormone-dependent breast carcinoma and other susceptible cancers; and gonadotropin-releasing hormone (GnRH) and analogues thereof that stimulate the release of luteinizing hormone (LH) and / or follicle-stimulating hormone (FSH) for the treatment of prostate carcinoma, for example, agonists and antagonists of LHRH, such as goserelin acetate and luprolide. Inhibitors of signal transduction pathways are those inhibitors that block or inhibit chemical processes that evoke an intracellular change. As used herein, this change is cell proliferation or differentiation. Signal transduction inhibitors useful in the present invention include inhibitors of receptor tyrosine kinases, non-receptor tyrosine kinases, SH2 / SH3 domain blockers, serine / threonine kinases, phosphatidylinositol-3 kinases, myo-inositol signaling, and Ras oncogenes. Several receptor protein kinases catalyze the phosphorylation of specific tyrosyl residues on various proteins involved in the regulation of cell growth. Such protein tyrosine kinases can be broadly classified as receptor or non-receptor kinases. Receptor tyrosine kinases are transmembrane proteins that have an extracellular ligand-binding domain, a transmembrane domain, and a tyrosine kinase domain. Receptor tyrosine kinases are involved in the regulation of cell growth and are usually called growth factor receptors. Inappropriate or uncontrolled activation of many of these kinases, that is, aberrant growth factor receptor kinase activity, for example, through overexpression or mutation, has been shown to result in uncontrolled cell growth. By IF-2019-16742483 -APN-ANP#INPI115 Page 115 of 402 Consequently, the aberrant activity of these kinases has been related to the growth of malignant tissues. Therefore, inhibitors of these kinases could provide treatment methods for cancer. Growth factor receptors include, for example, epidermal growth factor receptor (EGFr), platelet-derived growth factor receptor (PDGFr), erbB2, erbB4, ret, vascular endothelial growth factor receptor (VEGFr), tyrosine kinase with immunoglobulin-like domains and homology to epidermal growth factor (TIE-2), insulin growth factor-I (IGFI) receptor, macrophage colony-stimulating factor (cfms), BTK, ckit, cmet, receptors of fibroblast growth factor (FGF), Trk receptors (TrkA, TrkB, and TrkC), ephrin receptors (eph), and the RET proto-oncogene. Several growth receptor inhibitors are in development and include ligand antagonists, antibodies, tyrosine kinase inhibitors, and antisense oligonucleotides. Growth factor receptors and agents that inhibit growth factor reception function are described, for example, in Kath, John C., Exp. Opin. Ther. Patents (2000) 10(6):803-818; Shawver et al DDT Vol 2, No. 2 February 1997; and Lofts, F. J. et al, Growth factor receptors as targets, New Molecular Targets for Cancer Chemotherapy, ed. Workman, Paul and Kerr, David, CRC press 1994, London. Tyrosine kinases that are not growth factor receptor kinases are called nonreceptor tyrosine kinases. Nonreceptor tyrosine kinases useful in the present invention, which are targets or potential targets of anticancer drugs, include cSrc, Lek, Fyn, Yes, Jak, cAbl, FAK (focal adhesion kinase), Bruton's tyrosine kinase, and Bcr-. Abl. Such non-receptor kinases and agents that inhibit said non-receptor tyrosine kinase function are described in Sinh, S. and Corey, S.J., (1999) Journal of Hematotherapy and Stem Cell Research 8 (5): 465-80; and Bolen, J.B., Brugge, J.S., (1997) Annual review of Immunology. 15: 371-404. SH2 / SH3 domain blockers are agents that alter the binding of the SH2 or SH3 domain in a series of enzymes or adapter proteins including, the p85 subunit of PI3K, Src family kinases, adapter molecules (She, Crk, Nck, Grb2) and Ras-GAP. SH2 / SH3 domains as targets for anticancer drugs are described in Smithgall, T.E. (1995), Journal of Pharmacological and Toxicological Methods. 34(3) 125-32. Inhibitors of serine / threonine kinases, including blockers of the MAP kinase cascade including blockers of Raf kinases (rafk), extracellular or mitogen-regulated kinase (MEK), and extracellular regulated kinases (ERK); and blockers of members of the protein kinase C family, including blockers of PKC (alpha, beta, gamma, epsilon, mu, lambda, iota, zeta), IkB kinase family (IKKa, IKKb), family kinases PKB, members of the akt kinase family, and TGF beta receptor kinases. These serine / threonine IF-2019-16742483-APN-ANP#INPI116 Page 116 of 402 kinases and inhibitors thereof are described in Yamamoto, T., Taya, S., Kaibuchi, K., (1999), Journal of Biochemistry. 126 (5) 799-803; Brodt, P, Samani, A., and Navab, R. (2000), Biochemical Pharmacology, 60. 1101-1107; Massague, J., Weis-Garcia, F. (1996) Cancer Surveys. 27:41-64; Philip, P.A., and Harris, A.L. (1995), Cancer Treatment and Research. 78: 327, Lackey, K. etal Bioorganic and Medicinal Chemistry Letters, (10), 2000, 223-226; US Patent No. 6,268,391; and Martinez-Iacaci, L, et al, Int. J. Cancer (2000), 88(1), 44-52. Inhibitors of phosphatidylinositol-3 kinase members, including blockers of PI3-kinase, ATM, DNA-PK, and Ku are also useful in the present invention. Such kinases are described in Abraham, R.T. (1996), Current Opinion in Immunology. 8 (3) 412-8; Canman, C.E., Lim, D.S. (1998), Oncogene 17 (25) 3301-3308; Jackson, S.P. (1997), International Journal of Biochemistry and Cell Biology. 29 (7):935-8; and Zhong, H. et al, Cancer res, (2000) 60(6), 1541-1545. Also useful in the present invention are inhibitors of myo-inositol signaling, such as phospholipase C blockers and myo-inositol analogs. Such signal inhibitors are described in Powis, G., and Kozikowski A., (1994) New Molecular Targets for Cancer Chemotherapy ed., Paul Workman and David Kerr, CRC press 1994, London. Another group of signal transduction pathway inhibitors are Ras oncogene inhibitors. Such inhibitors include inhibitors of farnesyltransferase, geranyl-geranyl transferase, and CAAX proteases as well as antisense oligonucleotides, ribozymes, and immunotherapy. Such inhibitors have been shown to block ras activation in cells containing wild-type mutant ras, thereby acting as antiproliferative agents. Inhibition of the ras oncogene is described in Scharovsky, O.G., Rozados, V.R., Gervasoni, S.I. Matar, P. (2000), Journal of Biomedical Science. 7(4) 292-8; Ashby, M.N. (1998), Current Opinion in Lipidology. 9 (2) 99 - 102; and BioChim. Biophys. Acta, (19899) 1423(3):19-30. As mentioned above, antibodies antagonistic to receptor kinase ligand binding can also serve as inhibitors of signal transduction. This group of inhibitors of signal transduction pathways includes the use of humanized antibodies to the extracellular ligand-binding domain of receptor tyrosine kinases. For example, the EGFR-specific antibody, Imclone C225 (see Green, M.C. et al, Monoclonal Antibody Therapy for Solid Tumors, Cancer Treat. Rev., (2000), 26(4), 269286); the erbB2 antibody Herceptin® (see Tyrosine Kinase Signaling in Breast cancererbB Family Receptor Tyrosine Kinases, Breast cancer Res., 2000, 2(3), 176-183); and the VEGFR2-specific antibody 2CB (see Brekken, R.A. et al, Selective Inhibition of VEGFR2 Activity by a monoclonal Anti-VEGF antibody blocks tumor growth in mice, Cancer Res. IF-2019-16742483-APN-ANP#INPI117 Page 117 of 402 (2000) 60, 5117-5124). Anti-angiogenic therapeutic agents, including inhibitors of non-receptor MEK angiogenesis, may also be useful. Anti-angiogenic agents, such as those that inhibit the effects of vascular endothelial growth factor, for example, the anti-vascular endothelial cell growth factor antibody, bevacizumab [Avastin™], and compounds that function through other mechanisms (e.g. example, linomide, inhibitors of ανβ3 integrin function, endostatin and angiostatin). Agents used in immunotherapeutic regimens may also be useful in combination with compounds of formula (1-N), (1-P) or (I). Immunotherapeutic strategies, including, for example, ex vivo and in vivo strategies to increase the immunogenicity of the patient's tumor cells, such as transfection with attocins, such as interleukin 2, interleukin 4 or granulocyte-macrophage colony-stimulating factor, strategies to reducing the energy of T cells, strategies that use transfected immune cells, such as dendritic cells transfected with atocins, strategies that use tumor cells transfected with atocins, and strategies that use anti-idiotypic antibodies. Agents used in proapoptotic regimens (e.g., antisense oligonucleotides for bcl-2) may also be used in the combination of the present invention. Cell cycle signaling inhibitors inhibit molecules involved in cell cycle control. A family of protein kinases, called cyclin-dependent kinases (CDKs), and their interaction with a family of proteins called cyclins, control progression through the eukaryotic cell cycle. Coordinated activation and inactivation of different cyclin / CDK complexes is necessary for normal progression through the cell cycle. Several inhibitors of cell cycle signaling are in development. For example, examples of cyclin-dependent kinases, including CDK2, CDK4, and CDK6 and inhibitors therefor are described in, for example, Rosania et al, Exp. Opin. Ther. Patents (2000) 10(2):215-230. In one embodiment, the combination of the present invention comprises a compound of formula (1-N), (1-P) or (I), or a salt thereof, in particular a pharmaceutically acceptable salt thereof, and at least one antineoplastic agent selected from antimicrotubule agents, platinum coordination complexes, alkylating agents, antibiotic agents, topoisomerase II inhibitors, antimetabolites, topoisomerase I inhibitors, hormones and hormonal analogues, signal transduction pathway inhibitors, tyrosine angiogenesis MEK inhibitors receptor, immunotherapeutic agents, proapoptotic agents, and cell cycle signaling inhibitors. In one embodiment, the combination of the present invention comprises a compound of formula (l-N), (l-P) or (I), or a salt thereof, in particular a pharmaceutical salt IF-2019-16742483-APN-ANP#INPll 18 Page 118 of 402 acceptable thereof, and at least one antineoplastic agent which is an anti-microtubule agent selected from diterpenoids and vinca alkaloids. In a further embodiment, at least one antineoplastic agent is a diterpenoid. In a further embodiment, at least one antineoplastic agent is a vinca alkaloid. In one embodiment, the combination of the present invention comprises a compound of formula (1-N), (1-P) or (I), or a salt thereof, in particular a pharmaceutically acceptable salt thereof, and at least one antineoplastic agent, which It is a platinum coordination complex. In a further embodiment, at least one antineoplastic agent is paclitaxel, carboplatin, or vinorelbine. In a further embodiment, at least one antineoplastic agent is carboplatin. In a further embodiment, at least one antineoplastic agent is vinorelbine. In a further embodiment, at least one antineoplastic agent is paclitaxel. In one embodiment, the combination of the present invention comprises a compound of formula (1-N), (1-P) or (I), or a salt, in particular a pharmaceutically acceptable salt thereof, and at least one antineoplastic agent that is an inhibitor of signal transduction pathways. In a further embodiment, the signal transduction pathway inhibitor is an inhibitor of a growth factor receptor kinase such as VEGFR2, TIE2, PDGFR, BTK, erbB2, EGFr, IGFR-1, TrkA, TrkB, TrkC, or c -fms. In a further embodiment, the signal transduction pathway inhibitor is an inhibitor of a serine / threonine kinase rafk, akt, or PKCzeta. In a further embodiment, the signal transduction pathway inhibitor is an inhibitor of a non-receptor tyrosine kinase selected from the src kinase family. In a further embodiment, the signal transduction pathway inhibitor is a c-src inhibitor. In a further embodiment, the signal transduction pathway inhibitor is a Ras oncogene inhibitor selected from farnesyl transferase and geranylgeranyl transferase inhibitors. In a further embodiment, the signal transduction pathway inhibitor is an inhibitor of a serine / threonine kinase selected from the group consisting of PI3K. In a further embodiment, the signal transduction pathway inhibitor is a dual EGFr / erbB2 inhibitor, e.g., N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5 -({[2(methanesulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine. In one embodiment, the combination of the present invention comprises a compound of formula (1-N), (1-P) or (I), or a salt, in particular a pharmaceutically acceptable salt thereof, and at least one antineoplastic agent that is an inhibitor of cell cycle signaling. In a further embodiment, the cell cycle signaling inhibitor is an inhibitor of CDK2, CDK4 or CDK6. Additional examples of other therapeutic agents (e.g., antineoplastic agents) for use in combination or co-administered with a compound of formula (IIF-2019-16742483-APN-ANP#INPI119 Page 119 of 402 N), (I-P) or (I) are the immunomodulators. As used herein, immunomodulators refer to any substance, including monoclonal antibodies, that affects the immune system. Immunomodulators can be used as anti-neoplastic agents for cancer treatment. For example, immunomodulators include, but are not limited to, anti-CTLA-4 antibodies such as ipilimumab (YERVOY) and anti-PD-1 antibodies (Opdivo / nivolumab and Keytruda / pembrolizumab). Other immunomodulators include, but are not limited to, antibodies to ICOS, antibodies to OX-40, antibodies to PD-L1, antibodies to LAG3, antibodies to TIM-3, antibodies to 41BB, and antibodies to GITR. Additional examples of other therapeutic agents (antineoplastic agent) for use in combination or co-administered with a compound of the present invention are anti-PD-Ll agents. Anti-PD-Ll antibodies and methods for producing them are known in the art. Said antibodies for PD-L1 can be polyclonal or monoclonal, and / or recombinant, and / or humanized. Illustrative PD-L1 antibodies are disclosed in U.S. Patent Nos. 8,217,149, 8,383,796, 8,552,154, 9,212,224, and 8,779,108, and in U.S. Patent Publications Nos. Nos. 20110280877, 2014 / 0341902 and 20130045201. Additional exemplary antibodies to PD-L1 (also cited as CD274 or B7-H1) and methods of use are disclosed in US Patent Nos. 7,943,743, 8,168,179. ; and 7,595,048 WO2014055897, W02016007235 and US Patent Publications Nos. 20130034559, 20130034559 and 20150274835. Antibodies to PDL1 are under development as immunomodulatory agents or as immunomodulators for the treatment of cancer. In one embodiment, the antibody for PD-L1 is an antibody disclosed in US Patent No. 8,217,149. In another embodiment, the anti-PD-Ll antibody comprises the CDRs of an antibody disclosed in US Patent No. 8,217,149. In another embodiment, the antibody for PD-L1 is an antibody disclosed in US Patent No. 8,779,108. In another embodiment, the anti-PD-Ll antibody comprises the CDRs of an antibody disclosed in US Application No. 8,779,108. In another embodiment, the antibody for PD-L1 is an antibody disclosed in United States Patent Application Publication No. 20130045201. In another embodiment, the anti-PD-Ll antibody comprises the CDRs of an antibody disclosed in the United States Patent Application Publication No. 20130045201. In one embodiment, the anti-PD-Ll antibody is BMS-936559 (MDX-1105), which was described in WO 2007 / 005874. In another embodiment, the anti-PD-Ll antibody is MPDL3280A (RG7446). In another embodiment, the anti-PD-Ll antibody is MEDI4736, which is an anti-PD-Ll monoclonal antibody described in WO 2011 / 066389 and US 2013 / 034559. In another embodiment, the anti-PD-Ll antibody is IF-2019-16742483 -APN-ANP#INPI120 Page 120 of 402 TECENTRIQ™ (atezolizumab), which is an anti-PDLl cancer immunotherapy that was approved in May 2016 in the United States for specific types of bladder cancer. In another embodiment, the anti-PD-Ll antibody is YW243.55.S70 which is an anti-PD-Ll described in WO 2010 / 077634 and US Patent No. 8,217,149. Examples of anti-PD-Ll antibodies useful for the methods of the present invention, and methods for producing the same are described in PCT Patent Application WO 2010 / 077634, WO 2007 / 005874, WO 2011 / 066389, Patent of US 8,217,149, and US 2013 / 034559. Other examples of mAbs that bind human PD-L1, and useful in the treatment method, medicaments and uses of the present invention, are described in documents W02013 / 019906, W02010 / 077634 Al and US8383796. Specific anti-human PD-Ll mAb useful as a PD-1 antagonist in the treatment method, medicaments and uses of the present invention include MPDL3280A, BMS-936559, MEDI4736, MSB0010718C. Additional examples of other therapeutic agents (antineoplastic agent) for use in combination or co-administered with a compound of the present invention are PD-1 antagonists. PD-1 antagonist means any chemical compound or biological molecule that blocks the binding of PD-L1 expressed on a cancer cell to PD-1 expressed on an immune cell (T cell, B cell or NKT cell) and preferably also blocks the binding. from PD-L2 expressed on a cancer cell to PD-1 expressed on the immune cell. Alternative or synonymous names for PD-1 and its ligands include: PDCD1, PD1, CD279, and SLEB2 for PD-1; PDCD1L1, PDL1, B7H1, B7-4, CD274 and B7-H for PD-L1; and PDCD1L2, PDL2, B7-DC, Btdc, and CD273 for PD-L2. In any embodiment of the aspects or embodiments of the present invention in which a human individual is to be treated, the PD-1 antagonist blocks the binding of human PD-L1 to human PD-1, and preferably blocks the binding of both from PD-L1 as well as from human PD-L2 to human PD-1. The amino acid sequences of human PD-1 can be found in NCBI locus #: NP_005009. The amino acid sequences of human PD-L1 and PD-L2 can be found in NCBI locus #: NP_054862 and NP_079515, respectively. PD-1 antagonists useful in any aspect of the present invention include a monoclonal antibody (mAb), or an antigen-binding fragment thereof, that specifically binds to PD-1 or PD-L1, and preferably is specifically binds human PD-1 or human PD-L1. The mAB may be a human antibody, a humanized antibody, or a chimeric antibody, and may include a human constant region. In some embodiments, the human constant region is selected from the group consisting of IF-2019-16742483-APN-ANP#INPll 21 Page 121 of 402 the constant regions of IgGl, IgG2, IgG3 and IgG4, and in preferred embodiments, the human constant region is a constant region of IgGl or IgG4. In some embodiments, the antigen binding fragment is selected from the group consisting of Fab, Fab'-SH, F(ab')2, scFv and Fv fragments. Examples of mAbs that bind human PD-1, and that are useful in the various aspects and embodiments of the present invention, are described in US7488802, US7521051, US8008449, US8354509, US8168757, W02004 / 004771, W02004 / 072286 , W02004 / 056875, and US2011 / 0271358. Specific anti-human PD-1 mAb useful as a PD-1 antagonist in any of the aspects and embodiments of the present invention include: MK-3475, a humanized IgG4 mAb with the structure described in WHO Drug Information, Vol. 27 , No. 2, pages 161162 (2013) and comprising the heavy and light chain amino acid sequences shown in Figure 6; nivolumab, a human IgG4 mAb with the structure described in WHO Drug Information, Vol. 27, No. 1, pages 68-69 (2013) and comprising the heavy and light chain amino acid sequences shown in Figure 7; the humanized antibodies h409All, h409A16 and h409A17, which are described in document WO2008 / 156712, and AMP-514, which is under development by Medimmune. Other PD-1 antagonists useful in any of the aspects and embodiments of the present invention include an immunoadhesin that specifically binds to PD-1, and preferably binds specifically to human PD-1, for example, a fusion protein containing the extracellular or PD-1 binding part of PD-L1 or PD-L2 fused to a constant region, such as an Fe region of an immunoglobulin molecule. Examples of immunoadhesion molecules that specifically bind to PD-1 are described in W02010 / 027827 and WO2011 / 066342. Specific fusion proteins useful as a PD-1 antagonist in the treatment method, medications and uses of the present invention include AMP-224 (Also known as B7-DCIg), which is a PD-L2 fusion protein. -FC and that binds to human PD-1. KEYTRUDA / pembrolizumab is an anti-PD-1 antibody marketed by Merck for the treatment of lung cancer. The amino acid sequence of pembrolizumab and methods of using it are disclosed in US Patent No. 8,168,757. Opdivo / nivolumab is a fully human monoclonal antibody marketed by Bristol Myers Squibb directed against the human cell surface negative immunomodulatory receptor PD-1 (programmed death-1 or programmed cell death-1 / PCD-1) with immunopotentiating activity. Nivolumab binds to and blocks the activation of PD-1, a transmembrane protein of the Ig superfamily, through its ligands, PD-L1 and PD-L2, resulting in T cell activation and cell-mediated immune responses. IF-2019-16742483 -APN-ANP#INPI122 Page 122 of 402 against tumor cells or pathogens. Activated PD-1 negatively regulates T cell activation and effector function by suppressing activation of the PI3K / Akt pathway. Other names for nivolumab include: BMS-936558, MDX-1106, and ONO-4538. The amino acid sequence for nivolumab and methods of using and producing it are disclosed in US Patent No. 8,008,449. Additional examples of other therapeutic agents (antineoplastic agent) for use in combination or co-administered with a compound of formula (l-N), (l-P) or (I) are antibodies to ICOS. ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28, Nature, 397: 263-266 (1999)). Activation of ICOS occurs by binding through ICOS-L (B7RP-1 / B7-H2). Neither B7-1 nor B7-2 (ligands for CD28 and CTLA4) bind or activate ICOS. However, ICOS-L has been shown to bind weakly to both CD28 and CTLA-4 (Yao S et al., B7-H2 is a costimulatory ligand for CD28 in human, Immunity, 34(5); 729-40 (2011)). ICOS expression appears to be restricted to T cells. ICOS expression levels vary between different T cell subsets and with T cell activation status. ICOS expression has been demonstrated in resting TH17, follicular T cells. collaborators (TFH) and regulatory Ts (Treg); however, unlike CD28; it is not expressed at a high level in populations of TH1 and TH2 effector T cells (Paulos CM et al., The inducible costimulator (ICOS) is critical for the development of human Thl7 cells, Sci Transí Med, 2(55); 55ra78 (2010 )). ICOS expression is largely induced in effector CD4+ and CD8+ T cells after activation by TCR coupling (Wakamatsu E, et al., Convergent and divergent effects of costimulatory molecules in conventional and regulatory CD4+ T cells, Proc Natal Acad Sci USA, 110(3); The CDRs of murine antibodies to human ICOS having agonist activity are shown in PCT / EP2012 / 055735 (WO 2012 / 131004). Antibodies to ICOS are also disclosed in WO 2008 / 137915, WO 2010 / 056804, EP 1374902, EP1374901, and EP1125585. Agonistic antibodies to ICOS or ICOS binding proteins are disclosed in W02012 / 13004, WO 2014 / 033327, WO2016 / 120789, US20160215059, and US20160304610. In one embodiment, agonist antibodies for ICOS include ICOS binding proteins or antigen binding parts thereof comprising one or more of: CDRH1 as set forth in SEQ ID NO: 1; CDRH2 as set forth in SEQ ID NO: 2; CDRH3 as set forth in SEQ ID NO: 3; CDRL1 as set forth in SEQ ID NO: 4; the IF-2019-16742483 -APN-ANP#INPI123 Page 123 of 402 CDRL2 as set forth in SEQ ID NO: 5 and / or CDRL3 as set forth in SEQ ID NO: 6 or a direct equivalent of each CDR wherein a direct equivalent has no more than two amino acid substitutions in said CDR as is disclosed in document WO2016 / 120789, which is incorporated herein by reference in its entirety. In one embodiment, the ICOS binding protein or the antigen binding portion thereof is an ICOS agonist antibody comprising a VH domain comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in the invention. SEQ ID NO: 7 and / or a VL domain comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 8 set forth in document WO2016 / 120789 wherein said ICOS binding protein binds specifically to human ICOS. In one embodiment, the ICOS binding protein is an ICOS agonist antibody comprising a Vh domain comprising the amino acid sequence set forth in SEQ ID NO: 7 and a VL domain comprising the amino acid sequence set forth in SEQ ID NO: : 8 as set forth in document WO2016 / 120789. Yervoy (ipilimumab) is a fully human CTLA-4 antibody marketed by Bristol Myers Squibb. The protein structure of ipilimumab and its methods of use are described in US Patent Nos. 6,984,720 and 7,605,238. CD134, also known as 0X40, is a member of the TNFR superfamily of receptors that is not constitutively expressed on naïve T cells, unlike CD28. 0X40 is a secondary costimulatory molecule, expressed 24 to 72 hours after its activation; Its ligand, OX40L, is also not expressed in resting antigen-presenting cells, but is expressed after activation. 0X40 expression is dependent on complete T cell activation; Without CD28, 0X40 expression is delayed and at four-fold lower levels. Antibodies to OX-40, OX-40 fusion proteins, and methods of using them are disclosed in United States Patent Nos.: US 7,504,101; US 7,758,852; US 7,858,765; US 7,550,140; US 7,960,515; WO2012027328; WO2013028231. In one embodiment, the antigen binding protein 0X40 is one disclosed in document WO2012 / 027328 (PCT / US2011 / 048752), with international filing date of August 23, 2011. In another embodiment, the antigen binding protein It comprises the CDRs of an antibody disclosed in document WO2012 / 027328 (PCT / US2011 / 048752), with international filing date of August 23, 2011, or CDRs with 90% identity with respect to the disclosed CDR sequences. In a further embodiment, the antigen binding protein comprises a VH, a VL, or both of an antibody disclosed in WO2012 / 027328 (PCT / US2011 / 048752), with international filing date of August 23, 2011, o a VH or a VL with 90% identity with respect to the VH sequences o IF-2019-16742483 - A PN - AN P# IN PI124 Page 124 of 402 VL disclosed. In another embodiment, the 0X40 antigen binding protein is disclosed in WO2013 / 028231 (PCT / US2012 / 024570), with international filing date of February 9, 2012, which is incorporated herein by reference at its entirety. In another embodiment, the antigen binding protein comprises the CDR of an antibody disclosed in WO2013 / 028231 (PCT / US2012 / 024570), with international filing date of February 9, 2012, or CDR with 90% identity with respect to the disclosed CDR sequences. In a further embodiment, the antigen binding protein comprises a VH, a VL, or both of an antibody disclosed in WO2013 / 028231 (PCT / US2012 / 024570), with international filing date of February 9, 2012, or a VH or a VL with 90% identity with respect to the disclosed VH or VL sequences. In one embodiment, the 0X0 antigen binding protein is an isolated agonist antibody for 0X40 comprising a light chain variable region having a sequence at least 90% identical to the sequence of SEQ ID NO: 10 such as set forth in WO2013 / 028231 and a heavy chain variable region having a sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 4, as set forth in WO2013 / 028231. In one embodiment, the 0X40 antigen binding protein is an isolated antibody comprising a light chain variable region comprising the amino acid sequence of SEQ ID NO: 10 as set forth in WO2013 / 028231 and a region heavy chain variable comprising the amino acid sequence of SEQ ID NO: 4, as set forth in WO2013 / 028231. Therefore, in one embodiment, methods of treatment are provided to a human in need thereof comprising administering a compound of formula (I-N), (I-P) or (I) or a salt thereof and at least one immunomodulator. In one embodiment, the immunomodulator is selected from an ICOS agonist antibody, an OX-40 antibody, or a PD-1 antibody. In one embodiment, the human has cancer. Also provided herein is the use of a compound of formula (I-N), (I-P) or (I), or a salt thereof in combination with at least one immunomodulator for the treatment of a human being in need thereof. Additional examples of other therapeutic agents for use in combination or co-administered with a compound of formula (I-N), (I-P) or (I), or a salt thereof are immunostimulating agents. As used herein, immunostimulating agent refers to any agent that can stimulate the immune system. As used herein, immunostimulating agents include, but are not limited to, vaccine adjuvants, such as Toll-like receptor agonists, Toll-like receptor blockers, IF-2019-16742483 -APN-ANP#INPI125 Page 125 of 402 T cells, such as mAbs for PD-1 and CTL4 and T cell checkpoint agonists, such as mAbs agonists for OX-40 and ICOS. As used herein, immunostimulating agent refers to any agent that can stimulate the immune system. As used herein, immunostimulating agents include, but are not limited to, vaccine adjuvants. The term Toll-like receptor (or TLR), as used herein, refers to a member of the Toll-like receptor protein family or a fragment thereof that perceives a microbial product and / or initiates a adaptive immune response. In one embodiment, a TLR activates a dendritic cell (DC). Toll-like receptors (TLRs) are a family of pattern recognition receptors that were initially identified as sensors of the innate immune system that recognize microbial pathogens. TLRs recognize distinct structures in microbes, often referred to as PAMPs (pathogen-associated molecular patterns). The binding of ligands to TLRs triggers a cascade of intracellular signaling pathways that induces the production of factors involved in inflammation and immunity. In humans, ten TLRs have been identified. TLRs that are expressed on the cell surface include TLR-1, -2, -4, -5, and -6, while TLR-3, -7 / 8, and -9 are expressed in the ER compartment. Subsets of human DCs can be identified based on distinct TLR expression patterns. As an example, the myeloid or conventional subset of DCs (mDCs) express TLRs 1-8 when stimulated, and a cascade of activation markers occurs (e.g., CD80, CD86, MHC class I and II, CCR7 ), proinflammatory atoxins, and chemokines. One result of this stimulation and resulting expression is antigen-specific priming of CD4+ and CD8+ T cells. These DCs acquire an increased capacity to capture antigens and present them in an appropriate manner to T cells. In contrast, the plasmacytoid subset of DCs (pDCs) express only TLR7 and TLR9 upon activation, with the consequent activation of NK cells as well. as T cells. Since dying tumor cells can adversely affect DC function, it has been suggested that DC activation with TLR agonists may be beneficial for priming antitumor immunity in a Immunotherapy strategy for cancer treatment. It has also been suggested that successful treatment of breast cancer using radiation and chemotherapy requires activation of TLR4. TLR agonists known in the art and useful in the present invention include, but are not limited to, the following: Pam3Cys, a TLR1 / 2 agonist; CFA, a TLR2 agonist; MALP2, a TLR2 agonist; Pam2Cys, a TLR2 agonist; FSL-I, a TLR-2 agonist; Hib-OMPC, a TLR-2 agonist; polyinosinic:polycytidylic acid (Poly I:C), a TLR3 agonist; polyadenosine-polyuridylic acid (poly AU), a TLR3 agonist; acid IF-2019-16742483-APN-ANP#INPI126 Page 126 of 402 polyinosinic-polycytidylic stabilized with poly-L-lysine and carboxymethylcellulose (Hiltonol), a TLR3 agonist; bacterial flagellin, a TLR5 agonist; imiquimod, a TLR7 agonist; resiquimod, a TLR7 / 8 agonist; loxoribin, a TLR7 / 8 agonist; and unmethylated CpG dinucleotide (CpG-ODN), a TLR9 agonist. Additional TLR agonists known in the art and useful in the present invention also include, but are not limited to, alkyl glucosamine phosphates (AGPs) which bind to the TLR4 receptor and are known to be useful as vaccine adjuvants and immunostimulant agents. to stimulate cytokine production, activate macrophages, promote the innate immune response, and increase antibody production in immunized animals. An example of a naturally occurring TLR4 agonist is bacterial LPS. An example of a semisynthetic TLR4 agonist is monophosphoryl lipid A (MPL). AGPs and their immunomodulatory effects through TLR4 are disclosed in patent publications such as WO 2006 / 016997, WO 2001 / 090129, and / or US Patent No. 6,113,918 and have been reported in the literature . Additional AGP derivatives are disclosed in US Patent No. 7,129,219, US Patent No. 6,525,028 and US Patent No. 6,911,434. Certain AGPs act as TLR4 agonists, while others are recognized as TLR4 antagonists. In one embodiment, the immunostimulating agent for use in combination with the compounds of the present invention is a TLR4 agonist. In one embodiment, TLR4 agonists are cited as CRX-601 and CRX-527. Their structures are set out below: (CRX-601) IF-2019-16742483-APN-ANP#INPI 127 Page 127 of 402 Furthermore, another preferred embodiment employs the TLR4 agonist, CRX 547 having the structure shown. CRX 547 Additional embodiments include AGPs, such as CXR 602 or CRX 526 that provide increased stability to AGPs having shorter secondary acyl or alkyl chains. IF-2019-16742483-APN-ANP#INPI128 Page 128 of 402 \CRX-526 Therefore, in one embodiment, methods of treatment are provided to a human in need thereof comprising administering a compound of formula (l-N), (l-P) or (I) or a salt thereof and at least one immunostimulating agent. In one embodiment, the immunostimulating agent is a TLR4 agonist. In one embodiment, the immunostimulating agent is an AGP. In yet another embodiment, the TLR4 agonist is selected from a compound having the formula CRX-601, CRX-527, CRX-547, CRX-602 or CRX-526. In one embodiment, the human has cancer. Also provided herein is the use of a compound of formula (l-N), (l-P) or (I), or a salt thereof in combination with at least one immunostimulating agent for the treatment of a human being in need thereof. IF-2019-16742483-APN-ANP#INPI129 Page 129 of 402 In addition to the immunostimulating agents described above, the compositions of the present invention may further comprise other therapeutic agents that, due to their adjuvant nature, may act by stimulating the immune system to respond to cancer antigens present on inactivated cancer cells. Such adjuvants include, but are not limited to, lipids, liposomes, inactivated bacteria that induce innate immunity (e.g., inactivated or attenuated Listeria monocytogenes), compositions that mediate innate immune activation through (NOD)-like receptors (NLR), based on the retinoic acid-inducible gene similar to (RIG)-l (RLR), and / or the C-type lectin receptors (CLR). Examples of PAMPs include lipoproteins, lipopolypeptides, peptidoglycans, zymosan, lipopolysaccharide, neisserian porins, flagellin, profilin, galactoceramide, muramyl dipeptide. Peptidoglycans, lipoproteins, and lipoteichoic acids are components of the gram-positive cell wall. Lipopolysaccharides are expressed by most bacteria, MPL being just one example. Flagellin refers to the structural component of bacterial flagella that is secreted by pathogenic and commensal bacteria. rt.-galactosylceramide (rt.-GalCer) is an activator of natural killer T (NKT) cells. Muramyl dipeptide is a bioactive peptidoglycan motif common to all bacteria. Due to their adjuvant qualities, TLR agonists are preferably used in combinations with other vaccines, adjuvants and / or immunomodulators, and can be combined in various combinations. Therefore, in certain embodiments, the compounds described herein of formula (I-N), (I-P) or (I) that bind STING and induce STING-dependent TBKI activation and an inactivated tumor cell that expresses and secretes one or more atocins that stimulate the induction, recruitment and / or maturation of DCs, as described herein can be co-administered with one or more TLR agonists for therapeutic purposes. Indoleamine 2,3-dioxygenase 1 (IDO1) is a key immunosuppressive enzyme that modulates the antitumor immune response by promoting the generation of regulatory T cells and blocking the activation of effector T cells, thereby facilitating tumor growth by allowing cancer cells to escape immune surveillance. (Lemos H; et al., Cancer Res. Apr 15, 2015;76(8):2076-81), (Munn DH, et at., Trends Immunol, Mar 2016;37(3): 193-207 ). Additional active ingredients (antineoplastic agents) for use in combination or co-administered with the compounds of formula (I-N), (I-P) or (I) invented herein are IDO inhibitors. Epacadostat, ((Z)-N-(3-bromo-4-fluorophenyl)-N hydroxy-4-[2-(sulfamoylamino)ethylamino]-l,2,5-oxadiazol-3-carboxamidine) is an oral inhibitor highly potent and selective IDO1 enzyme that reverses tumor-associated immune suppression and restores effective antitumor immune responses. Epacadostat is released IF-2019-16742483 -APN-ANP#INPI130 Page 130 of 402 in US Patent No. 8,034,953. Additional examples of other therapeutic agents (antineoplastic agent) for use in combination or co-administered with a compound of formula (l-N), (l-P) or (I) are CD73 inhibitors and adenosine A2a and A2b antagonists. In one embodiment, the compound of the invention can be used with other therapeutic methods to treat infectious diseases. In particular, antiviral and antibacterial agents are provided. Compounds of formula (l-N), (l-P) or (I) and pharmaceutically acceptable salts thereof can be used in combination with at least one other therapeutic agent useful in the prevention or treatment of bacterial or viral infections. Examples of such agents include, without limitation: polymerase inhibitors, such as those disclosed in WO 2004 / 037818-Al, as well as those disclosed in WO 2004 / 037818 and WO 2006 / 045613; JTK-003, JTK-019, NM-283, HCV-796, R-803, R1728, R1626, as well as those disclosed in documents WO 2006 / 018725, WO 2004 / 074270, WO 2003 / 095441, US2005 / 0176701, WO 2006 / 020082, WO 2005 / 080388, WO 2004 / 064925, WO 2004 / 065367, WO 2003 / 007945, WO 02 / 04425, WO 2005 / 014543, WO 2003 / 000254, EP 1065 213, WO 01 / 47883, WO 2002 / 057287, WO 2002 / 057245 and similar agents; replication inhibitors, such as acyclovir, famciclovir, ganciclovir, cidofovir, lamivudine and similar agents; protease inhibitors, such as the HIV protease inhibitors saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, fosamprenavir, brecanavir, atazanavir, tipranavir, palinavir, lasinavir, and the HCV protease inhibitors BILN2061, VX-950, SCH503034 ; and similar agents; nucleoside and nucleotide reverse transcriptase inhibitors, such as zidovudine, didanosine, lamivudine, zalcitabine, abacavir, stavudine, adefovir, adefovir dipivoxil, fozivudine, todoxil, emtridtabine, alovudine, amdoxovir, elvucitabine, tenofovir disproxil fumarate, tenofovir alafenamide fumarate / hemifumarate, and similar agents; non-nucleoside reverse transcriptase inhibitors (including an agent that has antioxidative activity, such as immunocal, oltipraz etc.) such as nevirapine, delavirdine, efavirenz, loviride, immunocal, oltipraz, capravirine, TMC-278, TMC-125, etravirine, rilpivirine and similar agents; entry inhibitors, such as enfuvirtide (T-20), T-1249, PRO-542, PRO-140, TNX-355, BMS-806, 5-helix and similar agents; integrase inhibitors, such as dolutegravir, elvitegravir, raltegravir L-870,180 and similar agents; sprouting inhibitors, such as PA-334 and PA-457, and similar agents; chemokine receptor inhibitors, such as vicriviroc (Sch-C), Sch-D, TAK779, maraviroc (UK-427,857), TAK449, as well as those disclosed in WO 02 / 74769, WO 2004 / 054974, WO 2004 / 055012, WO 2004 / 055010, WO 2004 / 055016, WO 2004 / 055011, and WO 2004 / 054581, and similar agents; pharmacokinetic enhancers, such as cobicistat; neuraminidase inhibitors, such IF-2019-16742483-APN-ANP#INPI131 Page 131 of 402 such as CS-8958, zanamivir, oseltamivir, peramivir and similar agents; ion channel blockers, such as amantadine or rimantadine and similar agents; and RNA interference and antisense oligonucleotides, such as ISI-14803 and similar agents; antiviral agents with an undetermined mechanism of action, for example, those disclosed in WO 2005 / 105761, WO 2003 / 085375, WO 2006 / 122011, ribavirin, and similar agents. Compounds of formula (I-N), (I-P) or (I) and pharmaceutically acceptable salts thereof may also be used in combination with other therapeutic agents that may be useful in the treatment of herpesvirus infection associated with Kaposi's sarcoma. (KSHV and related to KSHV) include, without limitation, chemotherapeutic agents, such as bleomycin, vinblastine, vincristine, cyclophosphamide, prednisone, alitretinoin and liposomal anthracyclines, such as doxorubicin, daunorubicin, immunotherapeutic agents, such as rituximab, tocilizumab, siltuximab and others , such as paclitaxel and rapamycin. In one embodiment of the present invention, the at least one other therapeutic agent is an antimycobacterial agent or a bactericidal antibiotic. Compounds of formula (I-N), (I-P) or (I) and pharmaceutically acceptable salts thereof which may also be used in combination with at least one other therapeutic agent that may be useful in the treatment of TB infection {Mycobacterium tuberculosis and Tularemia {Franciseiia tuiarensis) include, without limitation, the first-line oral agents isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin, rifabutin; injectable agents, including kanamycin, amikacin, capreomycin, streptomycin; fluoroquinolones, including levofloxacin, moxifloxacin, ofloxacin; oral bacteriostatic agents, such as para-aminosalicylic acid, cycloserine, terizidone, thionamide, prothionamide; SQ-109 PNU-100480, Rifapentine Linezolid, PA-824 AZD5847, Gatifloxacin, Moxifloxacin, Sirturo (bedaquiline), Delamanid (OPC-67683) and agents with an undetermined mechanism of action in the treatment of drug-resistant TB, including clofazimine, linezolid, amoxicillin / clavulanate, thioaceta...

Claims

1. A heterocyclic amide compound characterized in that it is - dihydrogen phosphate 3-(((E)-6-carbamoyl-3-((E)-4-((E)-5-carbamoyl-2-((1-ethyl-3-methyl-1H-pyrazole-5-carbonyl)imino)-7-methoxy-2,3-dihydro-1H-benzo[d ]imidazol-1-yl)but-2-en-1-yl)-2-((1-ethyl-3-methyl-1H-pyrazol-5-carbonyl)imino)-2,3-dihydro-1H-benzo[d]imidazol-4-yl)oxy)propyl with the structure, FORMULA 1, and / or - dihydrogen phosphate (E)-3-((5-carbamoyl-1-(4-(5-carbamoyl-2-(1-ethyl-3-methyl-1H-pyrazol-5-carboxamido)-7-methoxy-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)-2-(1-ethyl-3-methyl-1H-pyrazol-5-carboxamido)-1H-benzo[d]imidazol-7-yl)oxy)propyl with the structure, FORMULA 2, or pharmaceutically acceptable salts thereof, or hydrates thereof. Seven claims follow.