Inhibitory compounds

Abstract

The present invention relates to certain compounds that function as inhibitors of enzymes which binds guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5' guanosine triphosphate (GTP) capped RNA, such as enzymes which comprise a RNA cap Guanine N-7 methyl transferase. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of viral infections, as well as other diseases or conditions in which activity of such enzymes is implicated. (Formula (I)

Description

INHIBITORY COMPOUNDSFIELD OF THE INVENTION

[0001] The present invention relates to certain compounds that function as inhibitors of enzymes which bind guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5’ guanosine triphosphate (GTP) capped RNA, such as enzymes which comprise a RNA cap Guanine N-7 methyl transferase. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of viral infections, as well as other diseases or conditions in which activity of such enzymes is implicated.BACKGROUND OF THE INVENTION

[0002] Higher eukaryotic cell messenger RNA (mRNA) and most viral RNA has a N7 methylated guanosine triphosphate modified cap structure at the 5'-end, commonly introduced by a guanosine methyl transferase and mediated by S-adenosylmethionine as cofactor (Shuman). In the case of eukaryotic cells this capping mechanism has many important biological functions including aiding nuclear export of precursor mRNA (Lewis et al) and protecting the mRNA from 5’ to 3’ degradative exonucleases (Schwer et al) and cytoplasmic P-bodies (Ramanathan et al). The capping mechanism also facilitates splicing and polyadenylation of mRNA and facilitates recognition of the mRNA by the eukaryotic translation initiation factor 4E (elF4E) for translation initiation (Ramanathan et al, Cowling).

[0003] For viruses from the family Coronaviridae, specifically the guanosine methyltransferase (MTase) domain of the viral non-structural protein NSP14 (Nonstructural Protein 14) catalyses the 5’ N7 cap methylation of nascent newly transcribed viral RNA, mimicking eukaryotic host cell mRNA 5’ cap and allowing the viral RNA to evade mechanisms of host cell RNA degradation and for the viral RNA to be directly translated by the host cell’s ribosomes. Viral RNA methyl transferases also play a role in protecting the virus from recognition by the hosts innate immune system leading to subsequent prolongation of viral replicative life (Ramdhan et al, Minkoff et al). For SARS-Cov-2, 5’ N7 methyl capping by NSP14 facilitates host cell immune evasion by allowing the viral RNA to commandeer the host cells own translation machinery to facilitate host translation inhibition (Hsu et al, Katahira et al). This prevents recognition by host’s foreign RNA sensors like RIG-1 and modulation of the host cell’s transcriptome to reflect changes in host cell immune components (Zaffagni et al): specifically the interferon pathway and interferon stimulating genes (ISGs) (Kim et al), blocking MDA-5 activity (Zust et al) and activating of the NF-kB pathway (Li et al). NSP14 has also been reported to reduce the accumulation of viral double-stranded (ds) RNAs and thus dampen the pathogen-associated molecular pattern (PAMP) mediated antiviral response(Becares et al).

[0004] NSP14 itself is a bifunctional protein encompassing a MTase catalytic domain at the C-terminus as well as a proof-reading exonuclease domain for replicative integrity at the N- terminus (ExON domain) (Ma et al). Previous studies on RNA viruses, like coronavirus (e.g., SARS-CoV-1 , which was the cause of SARS (severe acute respiratory syndrome) in 2002), have demonstrated that NSP14 is one of the key components involved in maintaining replication fidelity and therefore pathogenicity. The introduction of single amino acid substitutions to the active site of NSP14 methyl transferase are shown to render the enzyme catalytically inactive and to abrogate viral fitness (Ogando et al, Chen et al 2013) and reduce viral replication in various cellular models (Chen et al, 2009).

[0005] The impact of NSP14 inactivating mutations on viral pathogenicity has also been assessed in vivo. Inoculation of mice with MHV (Mouse Hepatitis Virus) virus harbouring mutant NSP14 was shown to result in a dramatically reduced viral load, to increase levels of IFN-p, a key antiviral cytokine, and to protect against infection induced weight loss, indicative of less severe disease. Significantly, by day 8 post infection, all animals treated with wild-type virus were deceased whilst all treated with mutant virus remained viable (Zhang et al).

[0006] The NSP14 methyl transferase domain protein sequence is highly conserved across all members of the family Coronaviridae including across coronaviruses known to be pandemic and endemic in humans (Rohaim et al, Pan et al). Homology of SARS-Cov-2 with SARS-CoV-1 and MERS is 100% within 6A of the cofactor site and bovine and murine coronavirus NSP14 are 89% identical to SARS-CoV-2 in this region, suggesting that ligands associated with SARS-Cov-2 methyl transferase binding site would have broad utility across the family.

[0007] The methyltransferase activity of NSP14 is a key mediator of Coronavirus pathogenicity and is essential for subsequent viral replication and fitness across the family Coronaviridae members. This includes all variants and subvariants of the human associated Betacoronavirus and Alphacoronavirus genus including SARS-Cov-1 , SARS-Cov-2, MERS- Cov, HCov-OC43, HCov-229E, HCov-HKU and HCov-NL63 as well as related family members of all Coronavirus genus which infect mammals and birds including those with zoonotic potential (Ogando et al).

[0008] Since the capping mechanism of the virus itself differs from the capping of messenger RNA in the host cell, it is possible to use the virus capping enzyme as a selective antiviral drug target (Bouvet et al., 2010). Several broad-spectrum drugs that inhibit viral capping systems via the cofactor binding site, such as AdoHcy, Sinefungin, and ATA, inhibit the activity of the methyltransferase of coronavirus (Bouvet et al., 2010). However, these non-specific drugs thatinhibit coronavirus methyltransferase cause significant side effects on the host itself.

[0009] In view of the ongoing SARS-CoV-2 spread that has caused the current worldwide COVID- 19 outbreak, it is desirable to have new methods of inhibiting SARS-CoV-2 viral replication and of treating COVID-19 in patients.

[0010] Inhibitors of NSP14 methyl transferase are expected to have combined additive or synergistic effects when dosed alongside other known antivirals which modulate the same pathways such a modulators of the immune response for example glucocorticoids such as Dexamethasone, cytokine antagonists such as Tocilizumab or Anakinra, Janus kinase inhibitors such as Baricitinib and Tofacitinib (Li et al) and MEK inhibitors such as ATR-002, Zapnometinib (Schreiber et al). Additive or synergistic effects might also be achieved from co-dosing with experimental senolytics such a Navitoclax and combined Quercetin / Dasatinib as well as Complement C5a inhibition (Lee et al 2021 , Kirkland et al 2020, Kalil et al 2022). Emerging drugs which target other non-structural protein (NSP) components of the Coronavirus replicative complex such as modulators of NSP10 / NSP14, NSP9, NSP10, NSP13 and NSP15 would be expected to have an additive or synergistic effect when combined with NSP14 methyl transferase inhibitors in-line with known efficacy already validated for mPro inhibitors such as Nirmatrelvir, Simnotrelvir and Ensetrelvir which ablate activity across multiple components of the viral RNA replicative complex, including NSP14.

[0011] NSP14 methyl transferase inhibitors might also be expected to act additively or synergistically in combination with anticoagulants such as heparin as well as antibodies vulnerable to resistance mechanisms which block the virus Spike protein, such as Bebtelovimab, Regdanvimab, Sotrovimab, Amubarvimab / Romlusevimab, Bamlanivimab / Etesevimab, Casirivimab / lmdevimab and Cilgavimab / Tixagevimab (Li et al 2023).

[0012] Specifically, inhibitors of NSP14 methyl transferase might be expected to promote synergistic effects with inhibitors of Coronavirus polymerases NSP12 such as Remdesivir, Deuremidevir and Molnupirivir (Basu et al 2021) as well as known antiviral inhibitors of IMPDH such as Ribavarin and Mycophenolic Acid (MPA) (Li et al 2022).

[0013] Targeting host cell mechanisms of mRNA recognition and modification to enhance the host’s anti-viral innate immune response would also be expected to show a synergistic or additive effect on co-dosing in combination with NSP14 inhibitors. For example, modulators of METTL3-METTL14, ALKBH5, FTO and YTHDF1 / 2 (Burgess et al 2021 , Li et al 2021 , Izadpanah et al 2022), Fibrillarin (Decle-Carrasco et al 2023, Deffrasnes et al 2016), NSun2 (Wang et al, 2023, Wnuk et al 2020) and ADAR1 (Adenosine Deaminase Acting on RNA 1) (Picardi et al 2021 , Pujantell et al 2017).

[0014] Guanosine N-7 methyl capping to modulate viral replication, translation and the effect on the host cell immune response is a common mechanism of viral disguise used by most viruses but the cap itself is introduced by diverse mechanisms; 3 general mechanisms to achieve this are used by viruses: 1) encoding their own capping enzymes, 2) hijacking the host cell capping machinery and 3) encoding enzymes and ancillary proteins to ‘cap snatch’ from host cell RNA. In viruses which encode their own capping machinery there’s a variety of family dependant enzyme cascades utilized by the virus for the incorporation of N7G involving methylation of GTP before or after transfer to the RNA by guanylyl transferase as the mono or the diphosphate intermediate. Example viruses of clinical importance which utilize their own guanosine N-7 methyl transferases for capping include from the family Pneumoviridae (Respiratory Syncytial Virus and Human Metapneumovirus), Paramyxoviridae (Human Parainfluenza Virus, Measles and Henipaviruses including Nipah), Flaviviridae (Dengue Virus, West Nile Fever, Yellow Fever, Zika, Japanese Encephalitis Virus, Tick Borne Encephalitis), Togaviridae (Rubella Virus, Chikungunya), Rhabdoviridae (Rabies) and Filoviridae (Ebola) (Decroly et al 2012) . The specific MOA of the inhibitors herein might enable cross inhibitory reactivity with other viral guanosine N7 methyl transferases, or other enzymes and ancillary proteins in the capping cascade, especially positive sense RNA methyl transferases but also not discounting those targeting negative sense RNA and DNA. For example, viruses from the same phylogenetic order as the family Coronavirus have structural similarities suggesting crossover, including other Nidovirales such as Berne virus, as well as other positive sense single stranded viruses in the orders Amarillovirales and Alpha-like viruses such as Zika virus and Dengue virus (Rhamdan et al). The compounds described herein may also target negative strand N7 guanosine methyl capping enzymes and includes multiple Mononegavirales viruses such as Rabies virus, Ebola virus, RSV (Respiratory Syncytial Virus), human Metapneumovirus and measles.

[0015] Throughout the SARS-CoV2 pandemic large numbers of SARS-CoV2 variants have emerged in the population. Inhibitors of NSP14 would be expected to be active across SARS- CoV2 variants providing a further therapeutic option to treat new emerging variants of concern, variants of interest and variants under monitoring. For example the currently circulating Omicron and it’s subvariants: EG.5, FL.1.5.1 , XBB.1.16, XBB.1.16.6, HV.1 , XBB.2.3, XBB.1.16.1 , XBB.1.5.70, XBB.1.16.11 , XBB, XBB.1.5, XBB.1.9.1 , GE.1 , EG.6.1 , XBB.1 .5.72, XBB.1.42.2, XBB.1.9.2, XBB.1.5.68, XBB.1.5.10, XBB.2.3.8, CH.1.1 , FD.1.1 , XBB.1.5.59, FE.1.1 , EU.1.1 , XBB.1.5.1 , BQ.1 , BA.2.12.1 , B.1.1.529, BA.5 and FD.2. This does not discount emerging strains highlighted by the CDC, the ECDC and WHO and includes strains from legacy variants and subvariants from Delta, Beta and Alpha strains. NSP14 inhibitors would also be expected to be active against emerging coronavirus with potential for zoonotictransmission to humans, for example the bat SARS-like WIV-1 (Menachery et al 2016) as well as those predicted emerging variants from modelling (Predict Consortium, Panditi et al 2022) as well as scientific expert and evidence-based prediction (Spillover. Global, Grange et al 2020).

[0016] NSP14 inhibitors would also be expected to be active against members of the family Coronaviridae pandemic, endemic and emerging in animal species and related to severe animal disease, for example Avian Infectious Bronchitis virus (IBV), Bovine coronavirus, Feline Infectious Peritonitis virus, Murine Coronavirus (MHV) and the Porcine Epidemic Diarrhea Virus (Oganda et al, 2021).

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R.; Kouzarides, T.; Stapleford, K. A.; Wilson, A. C.; Mohr, I. Targeting the m6A RNA Modification Pathway Blocks SARS- CoV-2 and HCoV-OC43 Replication. Genes Dev. 2021 , 35 (13-14), 1005-1019. https: / / doi.org / 10.1101 / gad.348320.121.Li, N.; Hui, H.; Bray, B.; Gonzalez, G. M.; Zeller, M.; Anderson, K. G.; Knight, R.; Smith, D.; Wang, Y.; Carlin, A. F.; Rana, T. M. METTL3 Regulates Viral M6A RNA Modification and Host Cell Innate Immune Responses during SARS-CoV-2 Infection. Cell Reports 2021 , 35 (6), 109091. https: / / doi.Org / 10.1016 / j.celrep.2O21.109091.Izadpanah, A.; Rappaport, J.; Datta, P. K. Epitranscriptomics of SARS-CoV-2 Infection. Front. Cell Dev. Biol. 2022, 10, 849298. https: / / doi.org / 10.3389 / fcell.2022.849298.Decle-Carrasco, S.; Rodriguez-Pina, A. L.; Rodriguez-Zapata, L. C.; Castano, E. Current Research on Viral Proteins That Interact with Fibrillarin. Mol Biol Rep 2023, 50 (5), 4631- 4643. https : / / doi . org / 10.1007 / s 11033-023-08343-2. Deffrasnes. C.; Marsh, G. A.; Foo, C. H.; Rootes, C. L.; Gould, C. M.; Grusovin, J.; Monaghan, P.; Lo, M. K.; Tompkins, S. M.; Adams, T. E.; Lowenthal, J. W.; Simpson, K. J.; Stewart, C. R.; Bean, A. G. D.; Wang, L.-F.Genome-Wide SiRNA Screening at Biosafety Level 4 Reveals a Crucial Role for Fibrillarin in Henipavirus Infection. PLoS Pathog 2016, 12 (3), e1005478. https: / / d0i.0rg / l 0.1371 / iournal.ppat.1005478.Wang, H.; Feng, J.; Zeng, C.; Liu, J.; Fu, Z.; Wang, D.; Wang, Y.; Zhang, L.; Li, J.; Jiang, A.; He, M.; Cao, Y.; Yan, K.; Tang, H.; Guo, D.; Xu, K.; Zhou, X.; Zhou, L.; Lan, K.; Zhou, Y.; Chen, Y. NSUN2-Mediated m5C Methylation of IRF3 MRNA Negatively Regulates Type I Interferon Responses during Various Viral Infections. Emerging Microbes & Infections 2023, 12 (1), 2178238. https: / / doi.Org / 10.1080 / 22221751.2023.2178238Wnuk, M.; Slipek, P.; Dziedzic, M.; Lewinska, A. The Roles of Host 5-Methylcytosine RNA Methyltransferases during Viral Infections. UMS 2020, 21 (21), 8176. https: / / doi.org / 10.3390 / ijms21218176.Picardi, E.; Mansi, L.; Pesole, G. Detection of A-to-l RNA Editing in SARS-COV-2. Genes 2021 , 13 (1), 41. https: / / doi.org / 10.3390 / genes13010Q41.Pujantell, M.; Riveira-Muhoz, E.; Badia, R.; Castellvi, M.; Garcia-Vidal, E.; Sirera, G.; Puig, T.; Ramirez, C.; Clotet, B.; Este, J. A.; Ballana, E. RNA Editing by ADAR1 Regulates Innateand Antiviral Immune Functions in Primary Macrophages. Sci Rep 2017, 7 (1), 13339. https: / / doi.Org / 10.1038 / S41598-017-13580-0.Decroly, E.; Ferron, F.; Lescar, J.; Canard, B. Conventional and Unconventional Mechanisms for Capping Viral MRNA. Nat Rev Microbiol 2012, 10 (1), 51-65. https: / / d0i.0rg / l 0.1038 / nrmicro2675.Ramdhan, P.; Li, C. Targeting Viral Methyltransferases: An Approach to Antiviral Treatment for SsRNA Viruses. Viruses 2022, 14 (2), 379. https: / / doi.org / 10.3390 / v14020379.SUMMARY OF THE INVENTION

[0018] In one aspect, the present invention provides a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

[0019] The present invention also relates to processes for the preparation of these compounds and to pharmaceutical compositions comprising them.

[0020] In another aspect, the present invention provides a pharmaceutical composition as defined herein which comprises a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and one or more pharmaceutically acceptable excipients.

[0021] In another aspect, the present invention provides a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, for use in therapy.

[0022] In another aspect, the present invention provides a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, for use in the inhibition of activity of an enzyme which binds guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5’ guanosine triphosphate (GTP) capped RNA.

[0023] In another aspect, the present invention provides a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, for use in the treatment of a disease or disorder in which the activity of an enzyme which binds guanosine monophosphate, guanosine diphosphate, guanosine triphosphate or 5’ guanosine triphosphate capped RNA is implicated.

[0024] In another aspect, the present invention provides a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, for use in inhibiting viral replication of a virus comprising an enzyme whichbinds guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5’ guanosine triphosphate (GTP) capped RNA.

[0025] Suitably, the enzyme which binds guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5’ guanosine triphosphate (GTP) capped RNA is an enzyme comprising a RNA cap Guanine N-7 methyl transferase, such as NSP14.

[0026] In another aspect, the present invention provides a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, for use in the treatment of a viral infection. Suitably, the viral infection is an infection described herein.

[0027] In another aspect, the present invention provides a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, for use in the treatment of a coronavirus infection. Suitably, the coronavirus infection is COVID- 19 (caused by SARS-CoV-2).

[0028] In another aspect, the present invention provides a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, for use in the treatment of COVID-19 (caused by SARS-CoV-2). Suitably, the compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or pharmaceutical composition as defined herein, are administered in combination with one or more additional therapeutic agents.

[0029] In another aspect, the present invention provides a method of inhibiting the activity of an enzyme which binds guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5’ guanosine triphosphate (GTP) capped RNA, the method comprising contacting a cell with a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein.

[0030] In another aspect, the present invention provides a method of treating a disease or disorder in which the activity of an enzyme which binds guanosine monophosphate, guanosine diphosphate, guanosine triphosphate or 5’ guanosine triphosphate capped RNA is implicated, said method comprising administering a therapeutically effective amount of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, to a patient in need of such treatment.

[0031] In another aspect, the present invention provides a method of inhibiting viral replication of a virus comprising an enzyme which binds guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5’ guanosine triphosphate (GTP)capped RNA, said method comprising contacting an infected cell with a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein.

[0032] Suitably, the enzyme which binds guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5’ guanosine triphosphate (GTP) capped RNA is an enzyme comprising a RNA cap Guanine N-7 methyl transferase, such as NSP14.

[0033] In another aspect, the present invention provides a method of treating a viral infection, said method comprising administering a therapeutically effective amount of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, to a patient in need of such treatment. Suitably, the viral infection is an infection described herein.

[0034] In another aspect, the present invention provides a method of treating a coronavirus infection, said method comprising administering a therapeutically effective amount of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, to a patient in need of such treatment. Suitably, the viral infection is an infection described herein. Suitably, the coronavirus infection is COVID-19 (caused by SARS-CoV-2).

[0035] In another aspect, the present invention provides a method of treating COVID-19 (caused by SARS-CoV-2)., said method comprising administering a therapeutically effective amount of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, to a patient in need of such treatment. Suitably, the compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or pharmaceutical composition as defined herein, are administered in combination with one or more additional therapeutic agents.

[0036] In another aspect, the present invention provides the use of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for the inhibition of activity of an enzyme which binds guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5’ guanosine triphosphate (GTP) capped RNA.

[0037] In another aspect, the present invention provides the use of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for the treatment of a disease or disorder in which the activity of an enzyme which binds guanosine monophosphate, guanosine diphosphate, guanosine triphosphate or 5’ guanosine triphosphate capped RNA is implicated.

[0038] In another aspect, the present invention provides the use of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for inhibiting viral replication of a virus comprising an enzyme which binds guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5’ guanosine triphosphate (GTP) capped RNA.

[0039] Suitably, the enzyme which binds guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5’ guanosine triphosphate (GTP) capped RNA is an enzyme comprising a RNA cap Guanine N-7 methyl transferase, such as NSP14.

[0040] In another aspect, the present invention provides the use of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for the treatment of a viral infection. Suitably, the viral infection is an infection described herein.

[0041] In another aspect, the present invention provides the use of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for the treatment of a coronavirus infection. Suitably, the coronavirus infection is COVID-19 (caused by SARS-CoV-2).

[0042] In another aspect, the present invention provides the use of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for the treatment of COVID- 19 (caused by SARS-CoV-2). Suitably, the compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or pharmaceutical composition as defined herein, are administered in combination with one or more additional therapeutic agents.

[0043] In another aspect, the present invention provides an inhibitor of an enzyme which binds guanosine monophosphate, guanosine diphosphate, guanosine triphosphate or 5’ guanosine triphosphate capped RNA, for use in the treatment of a viral infection. Suitably, the viral infection is any of the viruses described herein.

[0044] In another aspect, the present invention provides a method of treating a viral infection, said method comprising administering a therapeutically effective amount of an inhibitor of an enzyme which binds guanosine monophosphate, guanosine diphosphate, guanosine triphosphate or 5’ guanosine triphosphate capped RNA to a patient in need of such treatment.

[0045] In another aspect, the method of inhibiting viral replication of a virus, said method comprising contacting an infected cell with a therapeutically effective amount of an inhibitor of an enzyme which binds guanosine monophosphate, guanosine diphosphate, guanosinetriphosphate or 5’ guanosine triphosphate capped RNA.

[0046] In another aspect, the present invention provides a RNA cap Guanine N-7 methyl transferase inhibitor for use in the treatment of a viral infection. Suitably, the viral infection is any of the viruses described herein.

[0047] In another aspect, the present invention provides a method of treating a viral infection, said method comprising administering a therapeutically effective amount of a RNA cap Guanine N-7 methyl transferase inhibitor to a patient in need of such treatment.

[0048] In another aspect, the method of inhibiting viral replication of a virus, said method comprising contacting a viral RNA cap Guanine N-7 methyl transferase enzyme with a therapeutically effective amount of a viral RNA cap Guanine N-7 methyl transferase inhibitor.

[0049] In another aspect, the present invention provides a NSP14 inhibitor for use in the treatment of a viral infection. Suitably, the viral infection is any of the viruses described herein.

[0050] In another aspect, the present invention provides a NSP14 inhibitor for use in the treatment of a coronavirus infection. Suitably, the coronavirus infection is any of those described herein. More suitably, the coronavirus infection is COVID-19

[0051] In another aspect, the present invention provides a method of treating a coronavirus infection, said method comprising administering a therapeutically effective amount of a NSP14 inhibitor to a patient in need of such treatment.

[0052] In another aspect, the method of inhibiting viral replication of a coronavirus, said method comprising contacting an infected cell with a therapeutically effective amount of a RNA cap NSP14 inhibitor.

[0053] In another aspect, the present invention provides a NSP14 inhibitor for use in the treatment of a viral infection. Suitably, the viral infection is any of the viruses described herein.

[0054] In another aspect, the present invention provides a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, obtainable by, or obtained by, or directly obtained by a method of synthesis as defined herein.

[0055] In another aspect, the present invention provides novel intermediates as defined herein which are suitable for use in any one of the synthetic methods as set out herein.

[0056] Preferred, suitable, and optional features of any one particular aspect of the present invention are also preferred, suitable, and optional features of any other aspect.DETAILED DESCRIPTION OF THE INVENTIONDefinitions

[0057] Unless otherwise stated, the following terms used in the specification and claims have the following meanings set out below.

[0058] It is to be appreciated that references to “treating” or “treatment” include prophylaxis as well as the alleviation of established symptoms of a condition. “Treating” or “treatment” of a state, disorder or condition therefore includes: (1) preventing or delaying the appearance of clinical symptoms of the state, disorder or condition developing in a human or animal that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition, (2) inhibiting the state, disorder or condition, i.e., arresting, reducing or delaying the development of the disease or a relapse thereof (in case of maintenance treatment) or at least one clinical or subclinical symptom thereof, or (3) relieving or attenuating the disease, i.e., causing regression of the state, disorder or condition or at least one of its clinical or subclinical symptoms.

[0059] A “therapeutically effective amount” means the amount of a compound that, when administered to a human or animal (e.g. a mammal) for treating a disease, is sufficient to effect such treatment for the disease. The "therapeutically effective amount" will vary depending on the compound, the disease and its severity and the age, weight, etc., of the human or animal to be treated.

[0060] In this specification the term “alkyl” includes both straight and branched chain alkyl groups. References to individual alkyl groups such as “propyl” are specific for the straight chain version only and references to individual branched chain alkyl groups such as “isopropyl” are specific for the branched chain version only. For example, “Ci-ealkyl” includes Ci-4alkyl, Ci-3alkyl, propyl, isopropyl and f-butyl. A similar convention applies to other radicals, for example “phenyl(Ci-6alkyl)” includes phenyl(Ci-4alkyl), benzyl, 1-phenylethyl and 2-phenylethyl.

[0061] The term "(m-nC)" or “Cm-n”, or "(m-nC) group" or “Cm-n” used alone or as a prefix, refers to any group having m to n carbon atoms.

[0062] The term "alkenyl", as used herein, refers to an aliphatic group containing at least one double bond and is intended to include both "unsubstituted alkenyls" and "substituted alkenyls", the latter of which refers to alkenyl moieties having substituents replacing a hydrogen on one or more carbons of the alkenyl group. Such substituents may occur on one or more carbons that are included or not included in one or more double bonds. Moreover, such substituents include all those contemplated for alkyl groups, as discussed below, except where stability is prohibitive. For example, substitution of alkenyl groups by one or more alkyl, carbocyclyl, aryl, heterocyclyl, or heteroaryl groups is contemplated.

[0063] The term "alkynyl", as used herein, refers to an aliphatic group containing at least one triple bond and is intended to include both "unsubstituted alkynyls" and "substituted alkynyls", the latter of which refers to alkynyl moieties having substituents replacing a hydrogen on one or more carbons of the alkynyl group. Such substituents may occur on one or more carbons that are included or not included in one or more triple bonds. Moreover, such substituents include all those contemplated for alkyl groups, as discussed above, except where stability is prohibitive. For example, substitution of alkynyl groups by one or more alkyl, carbocyclyl, aryl, heterocyclyl, or heteroaryl groups is contemplated.

[0064] An “alkylene” group is an alkyl group that is positioned between and serves to connect two other chemical groups. Thus, “C1-3alkylene” means a linear saturated divalent hydrocarbon radical of one to three carbon atoms or a branched saturated divalent hydrocarbon radical of three atoms, for example, methylene, ethylene, propylene, and the like.

[0065] The term “Cm-ncycloalkyl” means a hydrocarbon ring containing from m to n carbon atoms, for example “C3-6cycloalkyl” means a hydrocarbon ring containing from 3 to 6 carbon atoms, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl. The term “Cm-ncycloalkyl” also encompasses non-aromatic saturated or partially saturated monocyclic, fused, bridged, or spiro bicyclic carbocyclic ring system(s). The term “Cm-ncycloalkyl” includes both monovalent species and divalent species. Monocyclic “Cm-ncycloalkyl” rings contain from about 3 to 12 (suitably from 3 to 8, most suitably from 5 to 6) ring carbon atoms. Bicyclic “Cm- ncycloalkyl” contain from 7 to 17 ring carbon atoms, suitably 7 to 12 ring carbon atoms. Bicyclic “Cm-ncycloalkyl” rings may be fused, spiro (e.g. spiro[3,3]heptane), or bridged ring systems (e.g. bicyclo[2.2.1]hept-2-ene and bicyclo[1.1.1]pentanyl).

[0066] The term “halo” or “halogeno” refers to fluoro, chloro, bromo and iodo.

[0067] The term “heterocyclyl”, “heterocyclic” or “heterocycle” means a non-aromatic saturated or partially saturated monocyclic, fused, bridged, or spiro bicyclic heterocyclic ring system(s). The term heterocyclyl includes both monovalent species and divalent species. Monocyclic heterocyclic rings contain from about 3 to 12 (suitably from 3 to 7, most suitably from 5 to 6) ring atoms, with from 1 to 5 (suitably 1 , 2 or 3) heteroatoms selected from nitrogen, oxygen or sulfur in the ring. Bicyclic heterocycles contain from 7 to 17 member atoms, suitably 7 to 12 member atoms, in the ring. Bicyclic heterocycles contain from about 7 to about 17 ring atoms, suitably from 7 to 12 ring atoms. Bicyclic heterocyclic(s) rings may be fused, spiro, or bridged ring systems. Examples of heterocyclic groups include cyclic ethers such as oxiranyl, oxetanyl, tetrahydrofuranyl, dioxanyl, and substituted cyclic ethers. Heterocycles containing nitrogen include, for example, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, tetrahydrotriazinyl, tetrahydropyrazolyl, and the like. Typical sulfur containing heterocyclesinclude tetrahydrothienyl, dihydro-1 , 3-dithiol, tetrahydro-2 / 7-thiopyran, and hexahydrothiepine. Other heterocycles include dihydro-oxathiolyl, tetrahydro-oxazolyl, tetrahydro-oxadiazolyl, tetrahydrodioxazolyl, tetrahydro-oxathiazolyl, hexahydrotriazinyl, tetrahydro-oxazinyl, morpholinyl, thiomorpholinyl, tetrahydropyrimidinyl, dioxolinyl, octahydrobenzofuranyl, octahydrobenzimidazolyl, and octahydrobenzothiazolyl. For heterocycles containing sulfur, the oxidized sulfur heterocycles containing SO or SO2 groups are also included. Examples include the sulfoxide and sulfone forms of tetrahydrothienyl and thiomorpholinyl such as tetrahydrothiene 1 ,1 -dioxide and thiomorpholinyl 1 ,1 -dioxide. A suitable value for a heterocyclyl group which bears 1 or 2 oxo (=0) or thioxo (=S) substituents is, for example, 2-oxopyrrolidinyl, 2-thioxopyrrolidinyl, 2-oxoimidazolidinyl, 2-thioxoimidazolidinyl, 2-oxopiperidinyl, 2,5-dioxopyrrolidinyl, 2,5-dioxoimidazolidinyl or 2,6-dioxopiperidinyl. Particular heterocyclyl groups are saturated monocyclic 3 to 7 membered heterocyclyls containing 1 , 2 or 3 heteroatoms selected from nitrogen, oxygen or sulfur, for example azetidinyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, morpholinyl, tetrahydrothienyl, tetrahydrothienyl 1 ,1-dioxide, thiomorpholinyl, thiomorpholinyl 1 ,1-dioxide, piperidinyl, homopiperidinyl, piperazinyl or homopiperazinyl. As the skilled person would appreciate, any heterocycle may be linked to another group via any suitable atom, such as via a carbon or nitrogen atom. However, reference herein to piperidino or morpholino refers to a piperidin-1-yl or morpholin-4-yl ring that is linked via the ring nitrogen.

[0068] By “bridged ring systems” is meant ring systems in which two rings share more than two atoms, see for example Advanced Organic Chemistry, by Jerry March, 4thEdition, Wiley Interscience, pages 131-133, 1992. Examples of bridged heterocyclyl ring systems include, aza-bicyclo[2.2.1]heptane, 2-oxa-5-azabicyclo[2.2.1]heptane, aza-bicyclo[2.2.2]octane, aza- bicyclo[3.2.1]octane, quinuclidine, 6-azabicyclo[3.1.1]heptane, 8-azabicyclo[3.2.1]octane, bicyclo[3.2.1]octane, 7-oxabicyclo[2.2.1]hept-2-ene and 3-oxa-8-azabicyclo[3.2.1]octane .

[0069] The term “heteroaryl” or “heteroaromatic” means an aromatic mono-, bi-, or polycyclic ring incorporating one or more (for example 1-4, particularly 1 , 2 or 3) heteroatoms selected from nitrogen, oxygen or sulfur. The term heteroaryl includes both monovalent species and divalent species. Examples of heteroaryl groups are monocyclic and bicyclic groups containing from five to twelve ring members, and more usually from five to ten ring members. The heteroaryl group can be, for example, a 5- or 6-membered monocyclic ring or a 9- or 10- membered bicyclic ring, for example a bicyclic structure formed from fused five and six membered rings or two fused six membered rings. Each ring may contain up to about four heteroatoms typically selected from nitrogen, sulfur and oxygen. Typically the heteroaryl ring will contain up to 3 heteroatoms, more usually up to 2, for example a single heteroatom. In one embodiment, the heteroaryl ring contains at least one ring nitrogen atom. The nitrogenatoms in the heteroaryl rings can be basic, as in the case of an imidazole or pyridine, or essentially non-basic as in the case of an indole or pyrrole nitrogen. In general the number of basic nitrogen atoms present in the heteroaryl group, including any amino group substituents of the ring, will be less than five.

[0070] Examples of heteroaryl include furyl, pyrrolyl, thienyl, oxazolyl, isoxazolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1 ,3,5-triazenyl, benzofuranyl, indolyl, isoindolyl, benzothienyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, benzothiazolyl, indazolyl, purinyl, benzofurazanyl, quinolyl, isoquinolyl, quinazolinyl, quinoxalinyl, cinnolinyl, pteridinyl, naphthyridinyl, carbazolyl, phenazinyl, benzisoquinolinyl, pyridopyrazinyl, thieno[2,3-b]furanyl, 2H-furo[3,2-b]-pyranyl, 5H-pyrido[2,3-d]-o-oxazinyl, 1 H-pyrazolo[4,3-d]-oxazolyl, 4H-imidazo[4,5-d]thiazolyl, pyrazino[2,3-d]pyridazinyl, imidazo[2,1-b]thiazolyl, imidazo[1 ,2-b][1 ,2,4]triazinyl. “Heteroaryl” also covers partially aromatic bi- or polycyclic ring systems wherein at least one ring is an aromatic ring and one or more of the other ring(s) is a non-aromatic, saturated or partially saturated ring, provided at least one ring contains one or more heteroatoms selected from nitrogen, oxygen or sulfur. Examples of partially aromatic heteroaryl groups include for example, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 2-oxo-1.2.3.4-tetrahydroquinolinyl, dihydrobenzthienyl, dihydrobenzfuranyl, 2,3-dihydro- benzo[1 ,4]dioxinyl, benzo[1 ,3]dioxolyl, 2,2-dioxo-1 ,3-dihydro-2-benzothienyl, 4, 5,6,7- tetrahydrobenzofuranyl, indolinyl, 1 ,2,3,4-tetrahydro-1 ,8-naphthyridinyl,1.2.3.4-tetrahydropyrido[2,3-b]pyrazinyl and 3,4-dihydro-2 / 7-pyrido[3,2-b][1 ,4]oxazinyl.

[0071] In the present invention “heteroaryl” also covers rings such as pyridones (e.g. 2- pyridonyl), pyrazinones and pyrimidinones (e.g. 4-pyrimidonyl).

[0072] Examples of five membered heteroaryl groups include but are not limited to pyrrolyl, furanyl, thienyl, imidazolyl, furazanyl, oxazolyl, oxadiazolyl, oxatriazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, triazolyl and tetrazolyl groups.

[0073] Examples of six membered heteroaryl groups include but are not limited to pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl and triazinyl.

[0074] A bicyclic heteroaryl group may be, for example, a group selected from: a benzene ring fused to a 5- or 6-membered ring containing 1 , 2 or 3 ring heteroatoms; a pyridine ring fused to a 5- or 6-membered ring containing 1 , 2 or 3 ring heteroatoms; a pyrimidine ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; a pyrrole ring fused to a 5- or 6-membered ring containing 1 , 2 or 3 ring heteroatoms;a pyrazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; a pyrazine ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; an imidazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; an oxazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; an isoxazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; a thiazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; an isothiazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; a thiophene ring fused to a 5- or 6-membered ring containing 1 , 2 or 3 ring heteroatoms; a furan ring fused to a 5- or 6-membered ring containing 1 , 2 or 3 ring heteroatoms; a cyclohexyl ring fused to a 5- or 6-membered heteroaromatic ring containing 1 , 2 or 3 ring heteroatoms; and a cyclopentyl ring fused to a 5- or 6-membered heteroaromatic ring containing 1 , 2 or 3 ring heteroatoms.

[0075] Particular examples of bicyclic heteroaryl groups containing a six membered ring fused to a five membered ring include but are not limited to benzfuranyl, benzthiophenyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzthiazolyl, benzisothiazolyl, isobenzofuranyl, indolyl, isoindolyl, indolizinyl, indolinyl, isoindolinyl, purinyl (e.g., adeninyl, guaninyl), indazolyl, benzodioxolyl and pyrazolopyridinyl groups.

[0076] Particular examples of bicyclic heteroaryl groups containing two fused six membered rings include but are not limited to quinolinyl, isoquinolinyl, chromanyl, thiochromanyl, chromenyl, isochromenyl, chromanyl, isochromanyl, benzodioxanyl, quinolizinyl, benzoxazinyl, benzodiazinyl, pyridopyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, phthalazinyl, naphthyridinyl and pteridinyl groups.

[0077] The term “aryl” means a cyclic or polycyclic aromatic ring having from 5 to 12 carbon atoms. The term aryl includes both monovalent species and divalent species. Examples of aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl and the like. In particular embodiment, an aryl is phenyl.

[0078] The term "optionally substituted" refers to either groups, structures, or molecules that are substituted and those that are not substituted.

[0079] Where optional substituents are chosen from “one or more” groups it is to be understood that this definition includes all substituents being chosen from one of the specified groups or the substituents being chosen from two or more of the specified groups.

[0080] The phrase “compound of the invention” means those compounds which are disclosed herein, both generically and specifically.Compounds of the invention

[0081] In one aspect, the present invention relates to compounds of the formula (I), or a pharmaceutically acceptable salt or solvate thereof,wherein:LA is a linker group of the formula -[CRL1RL2]m- in which m is an integer selected from 1, 2 or 3, and RL1and RL2are each independently selected from hydrogen or (1 -3C)alkyl;Ri is selected from aryl or heteroaryl, each of which being optionally substituted by one or more RIA substituents, wherein each RIA is independently selected from halo, cyano or a group of the formula:-WA-WB-WC whereinWA is absent or (1-6C)alkylene;WB is absent or selected from -O-, -S-, -N(R1 B)-, -C(O)-, -C(O)O-, -OC(O)-, - C(O)N(R1 B)-, -N(R1 B)C(O)-, -S(O)-, -S(O)2-, -S(O)(=NR1 B)-, -S(O)2N(R1 B)- or N(R1 B)SO2; wherein R1 Bis selected from hydrogen or (1 -3C)alkyl;Wc is selected from hydrogen, (1 -6C)alkyl), (3-6C)cycloalkyl or heterocyclyl; wherein Wc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1-4C)alkyl, NR1cR1 D, OR1c,C(O)R1c, C(O)OR1c, OC(O)R1c, C(O)N(R1 D)R1c, N(R1 D)C(O)R1c, S(O)qR1c(where q is 0, 1 or 2), S(O)(=N R1 D)R1c, S(O)2N(R1 D)R1cor N(R1 D)S(O)2R1c; wherein R1cand R1 Dare each independently selected from hydrogen, (1- 3C)alkyl or (3-6C)cycloalkyl, wherein (1 -3C)alkyl or (3-6C)cycloalkyl are each optionally substituted with one or more substituents selected from halo, cyano, hydroxy or NH2;Ring A is selected from:wherein:Xi is selected from O, S, N or NRXIN;X2 is selected from CRx2, O, S, N or NRX2N; wherein:RX2 is selected from hydrogen, hydroxy, halo, cyano, (1-3C)alkyl, (3- 6C)cycloalkyl, OR2A or NR2AR2B, wherein each of R2A and R2B are independently selected from hydrogen or (1 -3C)alkyl; wherein any (1 -3C)alkyl or (3-6C)cycloalkyl is optionally substituted by one or more substituents selected from halo, cyano, (1-3C)alkoxy or hydroxy; andRxiN and Rx2N are independently selected from hydrogen, (1-3C)alkyl or (3-6C)cycloalkyl, each of which being optionally substituted by one or more halo, oxo, methoxy or hydroxy substituents;R3xis selected from halo, cyano, or a group of the formula-XA-XB-XC whereinXA is absent or (1-6C)alkylene;XB is absent or selected from -O-, -S-, -N(R3A)-, -C(O)-, -C(O)O-, -OC(O)-, - N(R3A)C(O)-, -S(O)-, -S(O)2-, -S(O)(=NR3A)-, -S(O)2N(R3A)- or N(R3A)SO2; wherein R3A is selected from hydrogen or (1 -3C)alkyl;Xc is selected from hydrogen, (1 -6C)alkyl), (3-6C)cycloalkyl or heterocyclyl;wherein Xc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1-4C)alkyl, NR3BR3C, OR3B, C(O)R3B, C(O)OR3B, OC(O)R3B, C(O)N(R3C)R3B, N(R3C)C(O)R3B, S(O)qR3B(where q is 0, 1 or 2), S(O)(=NR3C)R3B, S(O)2N(R3C)R3B or N(R3C)S(O)2R3B; wherein R3B and R3c are each independently selected from hydrogen, (1- 3C)alkyl or (3-6C)cycloalkyl, wherein (1 -3C)alkyl or (3-6C)cycloalkyl are each optionally substituted with one or more substituents selected from halo, cyano, hydroxy or NH2; ii)wherein:Y1 is selected from CRY1or N;Y2 is selected from CRY2or N;Y3is selected from CRY3or N; wherein each of RY1, RY2and RY3are independently selected from hydrogen, hydroxy, halo, cyano, (1 -3C)alkyl, (3-6C)cycloalkyl, OR2a, NR2aR2b, wherein each of R2aand R2bare independently selected from hydrogen or (1 -3C)alkyl; wherein any (1 -3C)alkyl or (3-6C)cycloalkyl is optionally substituted by one or more substituents selected from halo, cyano, oxo, (1-3C)alkoxy or hydroxy; andR3yis selected from hydrogen, halo, cyano, or a group of the formula-XA-XB-XC whereinXA is absent or (1-6C)alkylene;XB is absent or selected from -O-, -S-, -N(R3A)-, -C(O)-, -C(O)O-, -OC(O)-, - N(R3A)C(O)-, -S(O)-, -S(O)2-, -S(O)(=NR3A)-, -S(O)2N(R3A)- or N(R3A)SO2; wherein R3A is selected from hydrogen or (1 -3C)alkyl;Xc is selected from hydrogen, (1 -6C)alkyl), (3-6C)cycloalkyl or heterocyclyl; wherein Xc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1-4C)alkyl, NR3BR3C, OR3B,C(O)R3B, C(O)OR3B, OC(O)R3B, C(O)N(R3C)R3B, N(R3C)C(O)R3B, S(O)qR3B(where q is 0, 1 or 2), S(O)(=NR3C)R3B, S(O)2N(R3C)R3B or N(R3C)S(O)2R3B; wherein R3B and R3c are each independently selected from hydrogen, (1- 3C)alkyl or (3-6C)cycloalkyl, wherein (1 -3C)alkyl or (3-6C)cycloalkyl are each optionally substituted with one or more substituents selected from halo, cyano, hydroxy or NH2;Z is selected from (1 -4C)alkyl, (3-12C)cycloalkyl, heterocyclyl, aryl, heteroaryl, (3- 7C)cycloalkyl(1-4C)alkyl, heterocyclyl(1-4C)alkyl, aryl(1-4C)alkyl, heteroaryl(1-4C)alkyl or NR6NR7N; wherein any alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, (3-7C)cycloalkyl(1- 4C)alkyl, heterocyclyl(1-4C)alkyl, aryl(1-4C)alkyl or heteroaryl(1-4C)alkyl, is optionally substituted by one or more substituents selected from halo, cyano, oxo, (1 -3C)alkyl, (2- 3C)alkenyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, aryl or heteroaryl, NRSCRSD, =CR6CR6D, OR6C, C(O)R6C, C(O)OR6C, C(O)N(R6D)R6C, N(R6D)C(O)R6C, SR6C, S(O)R6C, S(O)2R6c, S(O)2N(R6D)R6C or N(R6D)S(O)2R6C, (1-3C)alkyl, (1-3C)haloalkoxy); wherein R6c and RSD are each independently selected from hydrogen or (1 -3C)alkyl; wherein any (1 -3C)alkyl, (2-3C)alkenyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, aryl or heteroaryl substituent on group Z, including those in R6c and RSD, may be optionally further substituted by one or more substituents selected from halo, cyano, oxo, (1-3C)alkyl, (1-3C)haloalkyl, NRSERSF, OR6E, C(O)R6E, C(O)OR6E, OC(O)R6E, C(O)N(R6F)R6E, N(R6F)C(O)R6E, S(O)VR6E (where v is 0, 1 or 2), S(O)2N(R6F)R6E or N(R6F)S(O)2R6E; wherein R6E and RSF are each independently selected from hydrogen or (1 -3C)alkyl; wherein R6Nand R7Nare each independently selected from (1 -4C)alkyl or (3- 7C)cycloalkyl, wherein the (1 -4C)alkyl or (3-7C)cycloalkyl in R6Nand R7Nare optionally substituted with one of more substituents selected from halo, cyano, oxo, (1 -3C)alkyl, (2- 3C)alkenyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, aryl or heteroaryl, NRSGRSH, OR6G, C(O)R6G, C(O)OR6G, C(O)N(R6H)R6G, N(R6H)C(O)R6G, SR6G, S(O)R6G, S(O)2R6G, S(O)2N(R6H)R6G or N(R6H)S(O)2R6G; wherein R3H and R6c are each independently selected from hydrogen or (1 -3C)alkyl.

[0082] In a particular group of the compounds of the invention, the compounds have the structural formula (II) (a sub-definition of Formula (I)):wherein Ri, RXIN, X2, LA, RSX and Z each have any of the meanings as defined herein; or a pharmaceutically acceptable salt thereof.

[0083] In certain embodiments of the compounds of the present invention, if R1 is a phenyl ring, then the phenyl ring comprises at least one substituent other than hydrogen in the ortho position.

[0084] In certain embodiments of the compounds of the present invention, the compound is not:1,5-dimethyl-N-(2-methylbenzyl)-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;N-(2-methoxybenzyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H- pyrrole-2-carboxamide; orN-(2-chlorobenzyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide.

[0085] Particular compounds of the invention include, for example, compounds of Formula (I), or pharmaceutically acceptable salts thereof, wherein, unless otherwise stated, each of and any associated substituent groups has any of the meanings defined hereinbefore or in any one of paragraphs (1) to (137) hereinafter: -(1) LA is a linker group of the formula -[CRL1RL2]m- in which m is an integer selected from 1 or 2, and each occurrence of RL1and RL2are each independently selected from hydrogen or methyl.(2) LA is a linker group of the formula -[CRL1RL2]-, wherein RL1and RL2are independently selected from hydrogen or methyl.(3) LA is a linker group of the formula -[CH2]-.(4) R1 is selected from phenyl, naphthyl or mono or bicyclic heteroaryl, each of which being optionally substituted by one or more substituents RIA, wherein each RIA is independently selected from halo, cyano or a group of the formula:-WA-WB-WC whereinWA is absent or (1-6C)alkylene;WB is absent or selected from -O-, -S-, -N(R1 B)-, -C(O)-, -C(O)O-, -OC(O)-, - C(O)N(R1 B)-, -N(R1 B)C(O)-, -S(O)-, -S(O)2-, -S(O)(=NR1 B)-, -S(O)2N(R1 B)- or N(R1 B)S(O)2; wherein R1cis selected from hydrogen or methyl;Wc is selected from hydrogen, (1-6C)alkyl), (3-6C)cycloalkyl or 4- to 6- membered heterocyclyl; wherein Wc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1-2C)alkyl, NR1cR1 D, OR1c, C(O)R1c, C(O)N(R1 D)R1c, S(O)qR1c(where q is 0, 1 or 2), S(O)(=NR1 D)R1cor S(O)2N(R1 D)R1c; wherein R1cand R1care each independently selected from hydrogen, (1 -2C)alkyl or (3-6C)cycloalkyl, wherein any alkyl or cycloalkyl present in an optional substituent in a Wc group are each optionally substituted with one or more substituents selected from halo, cyano or NH2.(5) R1 is selected from phenyl, naphthyl or mono or bicyclic heteroaryl, each of which being optionally substituted by one or more substituents RIA, wherein each RIA is independently selected from halo, cyano or a group of the formula:-WA-WB-WC whereinWA is absent or (1-4C)alkylene;WB is absent or selected from -O-, -S-, -N(R1 B)-, -C(O)-, -C(O)O-, - C(O)N(R1 B)-, -N(R1 B)C(O)-, -S(O)-, -S(O)2-, -S(O)(=NRW)- or -S(O)2N(R1 B)-; wherein R1cis selected from hydrogen or methyl;Wc is selected from hydrogen, (1 -3C)alkyl), (3-6C)cycloalkyl 4- to 6- membered heterocyclyl; wherein Wc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1-2C)alkyl, NR1cR1 D, OR1c, C(O)R1c, C(O)N(R1c)R1c, S(O)qR1c(where q is 0, 1 or 2), S(O)(=NR1c)R1cor S(O)2N(RW)R1c; wherein R1cand R1care each independently selected from hydrogen or (1 -2C)alkyl, wherein any alkyl present in an optional substituentin a Wc group are each optionally substituted with one or more halo substituents.(6) Ri is selected from phenyl, naphthyl or mono or bicyclic heteroaryl, each of which being optionally substituted by one or more substituents RIA, wherein each RIA is independently selected from halo, cyano or a group of the formula:-WA-WB-WC whereinWA is absent or (1-3C)alkylene;WB is absent or selected from -O-, -S-, -N(R1 B)-, -C(O)-, -C(O)O-, - C(O)N(R1 B)-, -N(R1 B)C(O)-, -S(O)-, -S(O)2-, -S(O)(=NR1 B)- or -S(O)2N(R1 B)-; wherein R1cis selected from hydrogen or methyl;Wc is selected from hydrogen, (1 -2C)alkyl), (3-4C)cycloalkyl or a 4-membered heterocyclyl; wherein Wc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, methyl, NR1cR1 D, OR1cor C(O)N(R1 D)R1c; wherein R1cand R1care each independently selected from hydrogen or methyl, wherein any alkyl present in an optional substituent in a Wc group are each optionally substituted with one or more halo substituents.(7) Ri is selected from phenyl, naphthyl or mono or bicyclic heteroaryl, each of which being optionally substituted by one or more substituents RIA, wherein each RIA is independently selected from halo, cyano or a group of the formula:-WA-WB-WC whereinWA is absent or (1-3C)alkylene;WB is absent or selected from -O-, -S-, -N(R1 B)-, -C(O)-, -C(O)O-, - C(O)N(R1 B)-, -N(R1 B)C(O)-, -S(O)-, -S(O)2-, -S(O)(=NR1 B)- or -S(O)2N(R1 B)-; wherein R1cis selected from hydrogen or methyl;Wc is selected from hydrogen or (1 -2C)alkyl); wherein the (1 -2C)alkyl) in the Wc group is optionally further substituted by one or more fluoro substituents.(8) Ri is selected from phenyl, naphthyl or mono or bicyclic heteroaryl, each of which being optionally substituted by one or more substituents RIA, wherein each RIA is independently selected from halo, cyano or a group of the formula:-WA-WB-WC whereinWA is absent or (1-3C)alkylene;WB is absent or selected from -O-, -S-, -N(R1 B)-, -C(O)-, -C(O)O-, - C(O)N(R1c)- or -N(RiB)C(O)-; wherein R1 Bis selected from hydrogen or methyl;Wc is selected from hydrogen or (1 -2C)alkyl); wherein the (1 -2C)alkyl) in the Wc group is optionally further substituted by one or more fluoro substituents.(9) Ri is selected from phenyl, naphthyl, monocylic heteroaryl or bicyclic heteroaryl, each of which being optionally substituted by one or more substituents RIA, wherein each RIA is independently selected from fluoro, chloro, cyano, methyl, fluoromethyl (e.g. CF3, CHF2or CH2F), fluoromethoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.wherein:R1N and R2N are selected from hydrogen or (1 -2C)alkyl; and each of R4, R5, R6, R7, Rs, R4p, R5p, R6p, R7p, R8p, R9, R10, R11 , R12, R13, R14, R15, R16,R17, R19, R20, R21, R22, R23, R24, R25, R26, R27 and R28 are independently selected from hydrogen or a group RIA, each of R29, R30, R31 and R32 are independently selected from hydrogen or a group RIA, wherein each RIA is independently as defined anywhere herein.(11) R1 is: i) a group with a formula selected from:wherein:R4 is selected from hydrogen, halo (e.g. fluoro, chloro), cyano, (1 -3C)alkyl, (1- 3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; andRs, Re, R7 and Rs are each independently selected from hydrogen, halo, cyano, (1- 3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH ; ii) a group with a formula selected from:wherein:R9is selected from hydrogen, halo (e.g. fluoro, chloro), cyano, (1-3C)alkyl, (1- 3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; andR10, R11 , R12, R13, R14 and R15 are each independently selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; iv) a group with a formula:R16, R17, R18, R19, R20, R21 and R22are each indepedently selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; v) a group with a formula selected from:wherein:R23, R24, R25, R26, R27 and R28 are each independently selected from hydrogen, halo, cyano, (1 -3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2 or CH2F), (1-3C)haloalkoxy (e.g.OCF3, OCHF2 or OCH2F), NH2, OMe or OH;RiN is selected from hydrogen or (1-4C)alkyl; andR2N is selected from hydrogen or (1 -4C)alkyl; vi) a group with a formula:wherein:R29, R30, R31 and R32 are each independently selected from hydrogen, halo, cyano, (1 -3C)alkyl, (3-6C)cycloalkyl, (1-3C)haloalkyl (e.g. CF3, CHF2 or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH. (12) R1 is: i) a group with a formula selected from:wherein:R4is selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F) or OMe;Rs is selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2or OMe;Re is selected from hydrogen, halo, methyl or NH2;R7 is selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2or OMe; andRs is selected from hydrogen, halo (e.g. fluoro, chloro), cyano, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F) NH2or OMe;wherein:R4pis selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g.CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F) or OMe;R8Pis selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2, OMe;R6P is selected from hydrogen, halo, methyl, or NH2;R7P is selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2, OMe; andRsp is selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g.CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F) or OMe. iii) a group with a formula selected from:wherein:R9is selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy or OMe; R1cis selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), NH2, or OH; R11 is selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 orCH2F), NH2or OH;R12 is selected from hydrogen, halo or methyl;R13 is selected from hydrogen, halo or methyl;R14 is selected from hydrogen, halo, or methyl; and R15 is selected from hydrogen, halo or methyl; iv) a group with a formula:wherein:R16 is selected from hydrogen, halo, cyano, methyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F); R17 is hydrogen;R19 is hydrogen;R20 is hydrogen;R21 is hydrogen; andR22is hydrogen; v) a group with a formula selected from:wherein:R23 is selected from hydrogen, halo, methyl or (1-3C)haloalkyl; R24 is hydrogen;R25 is selected from hydrogen or NH2;R26 is hydrogen;R27 is hydrogen;R28 is hydrogen; R1N is selected from hydrogen or methyl; andR2N is selected from hydrogen or methyl; vi) a group with a formula:wherein:R2g, R30, R31 and R32 are each independently selected from hydrogen, halo, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g.OCF3, OCHF2or OCH2F), NH2, OMe or OH.(13) R1 is selected from: i) a group with the formula:wherein:R4 is selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g.CF3, CHF2or CH2F), fluoromethoxy (e.g. OCF3, OCHF2or OCH2F) or OMe;Rs is selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2or CH2F), fluoromethoxy (e.g. OCF3, OCHF2or OCH2F), NH2or OMe;Re is selected from hydrogen, halo, methyl or NH2;R7 is selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2or CH2F), fluoromethoxy (e.g. OCF3, OCHF2or OCH2F), NH2or OMe; andRs is selected from hydrogen, halo (e.g. fluoro, chloro), cyano, methyl, fluoromethyl (e.g. CF3, CHF2or CH2F), fluoromethoxy (e.g. OCF3, OCHF2or OCH2F) NH2or OMe;wherein:R4pis selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g.CF3, CHF2or CH2F), fluoromethoxy (e.g. OCF3, OCHF2or OCH2F) or OMe;R8Pis selected from hydrogen, fluoromethoxy (e.g. OCF3, OCHF2or OCH2F), NH2or OMe;RePis selected from hydrogen, halo (e.g. fluoro or chlro) or NH2;R7Pis selected from hydrogen, fluoromethoxy (e.g. OCF3, OCHF2or OCH2F), NH2or OMe; andRsp is selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g.CF3, CHF2or CH2F), fluoromethoxy (e.g. OCF3, OCHF2or OCH2F) or OMe; optionally wherein at least one of R4Pand R8Pis not hydrogen;wherein:R9is selected from hydrogen, halo (e.g. fluoro, chloro), methyl or fluoromethyl (e.g. CF3, CHF2or CH2F);R10 is selected from hydrogen or NH2;R11 is selected from hydrogen, NH2or OH;R12 is hydrogen;R13 is selected from hydrogen or methyl;R14 is selected from hydrogen or methyl; andR15 is hydrogen; or iv) a group with a formula:wherein:R29 is selected from hydrogen, halo, methyl, CF3, CHF2, CH2F), NH2, OMe or OH;R30 is selected from hydrogen, halo, methyl, CF3, CHF2, CH2F), NH2, OMe or OH;R31 is selected from hydrogen, halo, methyl, CF3, CHF2, CH2F), NH2, OMe orOH; andR32 is selected from hydrogen, halo, methyl, CF3, CHF2, CH2F), NH2, OMe or OH.(14) R1 is: i) a group with a formula:wherein:R4 is selected from hydrogen, methyl or halo (e.g. fluoro or chloro);Rs is selected from hydrogen or NH2;R7 is hydrogen; andRs is hydrogen or methoxy;wherein:R4pis selected from hydrogen or fluoro; R8Pis hydrogen; R6Pis hydrogen or chloro;R7Pis hydrogen; andRsp is selected from hydrogen or methoxy; wherein at least one of R4pand R8Pis not hydrogen;wherein:R9is selected from hydrogen, fluoro or chloro;R10 is hydrogen;R11 is selected from hydrogen or NH2;R12 is hydrogen;R13 is selected from hydrogen or methyl;R14 is hydrogen; andR15 is hydrogen.(15) R1 is selected from: i) a group with a formula:wherein:R4 is selected from hydrogen, methyl or halo (e.g. fluoro or chloro);R5 is selected from hydrogen or NH2;R7 is hydrogen; andRs is hydrogen or methoxy; ii) a group with a formula:wherein R4 is selected from hydrogen or halo; iii) a group with a formula:wherein R4 is selected from hydrogen, methyl or halo; and R7 is selected from hydrogen or NH2; iv) a group with a formula:wherein R7 is selected from hydrogen or NH2and Rs is selected from hydrogen or methyl; v) a group with a formula:wherein:R9is selected from hydrogen, fluoro, methyl or fluromethyl (e.g. CHF2); R11 is selected from hydrogen or NH2; andR13 is selected from hydrogen or methyl; vi) a group with a formula:wherein:R9is selected from hydrogen, fluoro, methyl or fluromethyl (e.g. CHF2);R11 is selected from hydrogen or NH2; and R13 is selected from hydrogen or methyl; vii) a group with a formula:wherein R9is selected from hydrogen, fluoro, methyl or CHF2; R11 is selected from hydrogen or NH2; and R13 is selected from hydrogen or methyl; or viii) a group with a formula:whereinR9is selected from hydrogen, methyl, fluoro or chloro;R11 is selected from hydrogen or NH2;R13 is selected from hydrogen or methyl.(16) RIN and R2N are selected from hydrogen or (1 -2C)alkyl.(17) RIN and R2N are selected from hydrogen or methyl.(18) R4 is selected from hydrogen, halo (e.g. fluoro, chloro), cyano, (1 -3C)alkyl, (1- 3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(19) R4 is selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F) or OMe.(20) R4 is selected from hydrogen, halo (e.g. fluoro or chloro) or methyl.(21) R5 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(22) R5 is selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2or OMe.(23) R5 is selected from hydrogen or NH2.(24) Re is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2 or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(25) Re is selected from hydrogen, halo, methyl or NH2.(26) Re is selected from hydrogen or NH2.(27) R7 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g.CF3, CHF2 or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(28) R7 is selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2or OMe.(29) R7 is selected from hydrogen or NH2.(30) Rs is selected from hydrogen, halo (e.g. fluoro, chloro), cyano, (1 -3C)alkyl, (1- 3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(31) Rs is selected from hydrogen, halo (e.g. fluoro, chloro), cyano, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F) NH2or OMe.(32) Re is selected from hydrogen, methyl or methoxy.(33) R9is selected from hydrogen, halo (e.g. fluoro, chloro), cyano, (1 -3C)alkyl, (1- 3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(34) R9is selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy or OMe.(35) R9is selected from hydrogen, halo (e.g. fluoro, chloro), methyl or fluoromethyl (e.g. CF3, CHF2or CH2F);(36) R9is selected from hydrogen, fluoro or chloro;(37) R1cis selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(38) R1cis selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), NH2, or OH.(39) R10 is selected from hydrogen or NH2.(40) R10 is selected from hydrogen.(41) R11 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2 or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(42) R11 is selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), NH2or OH.(43) R11 is selected from hydrogen, NH2or OH.(44) R11 is selected from hydrogen or NH2.(45) R12 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g.CF3, CHF2 or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe orOH.(46) R12 is selected from hydrogen, halo or methyl.(47) R12 is hydrogen.(48) R11 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2 or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(49) R11 is selected from hydrogen, halo or methyl;(50) R11 is selected from hydrogen or methyl.(51) R14 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g.CF3, CHF2 or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(52) R14 is selected from hydrogen, halo, or methyl.(53) R14 is selected from hydrogen or methyl.(54) R15 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g.CF3, CHF2 or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(55) Ris is selected from hydrogen, halo or methyl.(56) R15 is hydrogen.(57) R16 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(58) R16 is selected from hydrogen, halo, cyano, methyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F);(59) R16 is selected from hydrogen, halo, methyl, CF3, CHF2or CH2F;(60) R11 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(61) R11 is selected from hydrogen, halo, cyano, methyl, CF3, CHF2or CH2F, OCF3, OCHF2or OCH2F or OMe.(62) R11 is hydrogen.(63) R19 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(64) R19 is selected from hydrogen, halo, cyano, methyl, CF3, CHF2or CH2F, OCF3, OCHF2or OCH2F or OMe.(65) R19 is hydrogen.(66) R2O is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(67) R2O is selected from hydrogen, halo, cyano, methyl, CF3, CHF2or CH2F, OCF3, OCHF2or OCH2F or OMe.(68) R2O is hydrogen.(69) R2I is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(70) R2I is selected from hydrogen, halo, cyano, methyl, CF3, CHF2or CH2F, OCF3, OCHF2or OCH2F or OMe.(71) R2I is hydrogen.(72) R22is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(73) R22is selected from hydrogen, halo, cyano, methyl, CF3, CHF2or CH2F, OCF3, OCHF2or OCH2F or OMe.(74) R22 is hydrogen.(75) R23 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH;(76) R23 is selected from hydrogen, halo, cyano, methyl, (1-3C)haloalkyl, OCF3, OCHF2 or OCH2F or OMe.(77) R23 is selected from hydrogen, halo, methyl or (1-3C)haloalkyl;(78) R24 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2 or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(79) R24 is selected from hydrogen, halo, cyano, methyl, CF3, CHF2 or CH2F, OCF3, OCHF2 or OCH2F or OMe.(80) R24 is hydrogen.(81) R25 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2 or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(82) R25 is selected from hydrogen, halo, cyano, methyl, CF3, CHF2 or CH2F, OCF3, OCHF2 or OCH2F or OMe.(83) R25 is selected from hydrogen or NH2.(84) R26 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2 or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH;(85) R26 is selected from hydrogen, halo, cyano, methyl, CF3, CHF2 or CH2F, OCF3, OCHF2 or OCH2F or OMe.(86) R26 is hydrogen.(87) R27 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2 or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH;(88) R27 is selected from hydrogen, halo, cyano, methyl, CF3, CHF2 or CH2F, OCF3, OCHF2 or OCH2F or OMe.(89) R27 is hydrogen.(90) R28 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2 or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH;(91) R28 is selected from hydrogen, halo, cyano, methyl, CF3, CHF2 or CH2F, OCF3, OCHF2 or OCH2F or OMe.(92) R28 is hydrogen.(93) Ring A is selected from:wherein:Xi is selected from O, S, N or N RXI N;X2 is selected from CRX2, O, S, N or N RX2N; wherein:RX2is selected from hydrogen, (1 -3C)alkyl or (3-6C)cycloalkyl, wherein the (1- 3C)alkyl or (3-6C)cycloalkyl is optionally substituted by one or more substituents selected from halo, cyano, (1-2C)alkoxy or hydroxy;RXI N and RX2N are independently selected from hydrogen, (1 -3C)alkyl or (3- 6C)cycloalkyl, each of which being optionally substituted by one or more halo substituents; andRsx and Rsyare as defined anywhere herein;Y1 is selected from CRY1or N;Y2 is selected from CRY2or N; wherein each of RY1, RY2and RY3are independently selected from hydrogen, (1- 3C)alkyl or (3-6C)cycloalkyl, wherein the (1 -3C)alkyl or (3-6C)cycloalkyl is optionally substituted by one or more substituents selected from halo, cyano, (1-2C)alkoxy or hydroxy; andRsx and Rsyare as defined anywhere herein.(94) Ring A is selected from:wherein:Xi is selected from O, S, or N RXI N ; wherein RXI N is selected from hydrogen or (1 -3C)alkyl, wherein the alkyl is optionally substituted by one or more halo substituents; and X2 is selected from CRx2, O, S or N; wherein RX2is selected from hydrogen or methylY1 is selected from CRY1or N;Y2 is selected from CRY2or N; wherein each of RY1and RY2are independently selected from hydrogen or methyl; andRsx and Rsyare as defined anywhere herein.(95) Ring A is selected from:wherein:Xi is selected from O, S, or N RXI N ; wherein RXI N is selected from hydrogen or (1- 3C)alkyl, wherein the alkyl is optionally substituted by one or more fluoro substituentsX2 is selected from CRx2 or N; wherein RX2is selected from hydrogen or (1 -3C)alkyl, wherein the alkyl is optionally substituted by one or more fluoro substituents;Y1 is selected from CRYI or N; wherein RY1is selected from hydrogen or (1 -3C)alkyl, wherein the alkyl is optionally substituted by one or more fluoro substituents; andRsx and Rsyare each as defined anywhere herein.(96) Ring A is selected from:wherein:Xi is selected from N RXI N; wherein RXI N is selected from hydrogen or (1 -3C)alkyl optionally substituted by one or more fluoro substituents;X2 is selected from CRx2 or N; wherein RXI N is selected from hydrogen, methyl or ethyl; andRsx and Rsyare as defined anywhere herein.(97) Ring A is:wherein:Xi is selected from N RXI N; wherein RXI N is selected from hydrogen or (1 -3C)alkyl optionally substituted by one or more fluoro substituents;X2 is selected from CRx2 or N; wherein RXI N is selected from hydrogen, methyl or ethyl; andRsx is as defined anywhere herein.(98) Ring A is selected from:wherein RXI N is selected from hydrogen, methyl or ethyl, wherein the methyl and ethyl are optionally substituted by one or more fluoro substituents; andRsx is as defined anywhere herein.(98a) Ring A is selected from:wherein RXI N is selected from methyl or ethyl, wherein the methyl and ethyl are optionally substituted by one or more fluoro substituents; andRsx is as defined anywhere herein.(99) Ring A is:wherein RXIN is selected from hydrogen, methyl or ethyl, wherein the methyl and ethyl are optionally substituted by one or more fluoro substituents; andR3xis as defined anywhere herein.(99a) Ring A is:wherein RXIN is selected from methyl or ethyl; and Rsx is as defined anywhere herein.(100) Rsx and Rsyare selected from halo, cyano, or a group of the formula:-XA-XB-XC wherein:XA is absent or (1-4C)alkylene;XB is absent or selected from -O-, -S-, -N(RSA)-, -C(O)-, -C(O)O-, -OC(O)-, or - N(RSA)C(O)-; wherein RSA is selected from hydrogen or (1 -2C)alkyl;Xc is selected from hydrogen, (1 -6C)alkyl), (3-6C)cycloalkyl or heterocyclyl; wherein Xc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1-4C)alkyl, NRSBRSC, ORSB, C(O)RSB, C(O)ORSB, OC(O)RSB, C(O)N(R3C)R3B; wherein R3B and R3c are each independently selected from hydrogen, (1-3C)alkyl or (3-6C)cycloalkyl, wherein (1 -3C)alkyl or (3- 6C)cycloalkyl are each optionally substituted with one or more substituents selected from halo, cyano, hydroxy or NH2.(101) Rsx and Rsyare selected from halo, cyano, or a group of the formula:-XA-XB-XC wherein:XA is absent;XB is absent, -O-, or -N(RsA)-;Xc is selected from (1 -6C)alkyl) or (3-6C)cycloalkyl;wherein Xc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1-4C)alkyl, NRSBRSC, ORSB, C(O)RSB, C(O)ORSB, OC(O)RSB, C(O)N(R3C)R3B; wherein R3B and R3c are each independently selected from hydrogen or (1 -2C)alkyl.(102) Rsx and Rsyare selected from halo, cyano, or a group of the formula:-XA-XB-XC wherein:XA is absent;XB is absent;Xc is selected from (1 -3C)alkyl) or (3-6C)cycloalkyl; wherein Xc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1 -2C)alkyl, NRSBRSC or ORSB; wherein RSB and Rsc are each independently selected from hydrogen or methyl.(103) Rsx and Rsyare selected from halo, cyano, (1-2C)alkyl, cyclopropyl, wherein any (1- 2C)alkyl or cyclopropyl in a Rsxor Rsygroup is optionally substituted by one or more substituents selected from halo, hydroxy, NH2or cyano.(104) Rsx and Rsyare selected from fluoro, chloro, bromo, cyano, methyl or cyclopropyl, wherein methyl or cyclopropyl are optionally substituted by one or more substituents selected from fluoro, hydroxy or NH2.(104a) Rsx and Rsyare selected from fluoro, chloro, bromo, cyano, methyl or cyclopropyl, wherein methyl or cyclopropyl are optionally substituted by one or more fluoro substituents.(105) Z is selected from (1-4C)alkyl, (3-12C)cycloalkyl, heterocyclyl, phenyl, heteroaryl or NR6NR7N; wherein any (1-4C)alkyl, (3-12C)cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally substituted by one or more substituents selected from halo, cyano, oxo, (1- 3C)alkyl, (2-3C)alkenyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, aryl, heteroaryl, NRSCRSD, =CR6CR6D, OR6c, C(O)R6c, C(O)OR6c, C(O)N(R6D)R6C, N(R6D)C(O)R6C, SR6c, S(O)R6c or S(O)2R6c; wherein R6c and RSD are each independently selected from hydrogen or (1-3C)alkyl;wherein any (1 -3C)alkyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, aryl or heteroaryl substituent on group Z, including those in R6c and RSD, is optionally further substituted by one or more substituents selected from halo, cyano, oxo, (1 -3C)alkyl, (1-3C)haloalkyl, NRSERSF, ORSE, C(O)R6E, C(O)OReE or OC(O)R6E; wherein RSE and Rep are each independently selected from hydrogen or (1 -3C)alkyl; and wherein R6Nand R7Nare each independently selected from hydrogen, (1 -4C)alkyl or (3-6C)cycloalkyl; wherein R6Nand R7Nare each independently selected from (1 -4C)alkyl or (3-7C)cycloalkyl, wherein the (1 -4C)alkyl or (3-7C)cycloalkyl in R6Nand R7Nare optionally substituted with one of more substituents selected from halo, cyano, oxo, (1 -3C)alkyl, (2- 3C)alkenyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, aryl or heteroaryl, NRSGRSH, OR6G, C(O)R6G, C(O)OR6G, C(O)N(R6H)R6G, N(R6H)C(O)R6G, SR6G, S(O)R6G, S(O)2R6G, S(O)2N(R6H)R6G or N(R6H)S(O)2R6G; wherein RSH and R6c are each independently selected from hydrogen or (1 -3C)alkyl.(106) Z is selected from (3-12C)cycloalkyl, a 4- to 12-membered heterocyclic ring (including fused, bridged and spirocyclic heterocyclic rings), phenyl, mono- or bicyclic heteroaryl or NR6NR7N; wherein any (3-12C)cycloalkyl, a 4- to 12-membered heterocyclic ring, phenyl or mono- or bicyclic heteroaryl ring may be optionally substituted by one or more substituents selected from halo, cyano, oxo, (1-3C)alkyl, (2-3C)alkenyl, (3-6C)cycloalkyl, 4- to 7- membered heterocyclyl, phenyl, 5- or 6-membered heteroaryl, NRSCRSD, OR6c, C(O)R6c, C(O)OR6c, C(O)N(R6D)R6C, N(R6D)C(O)R6C, SR6c, S(O)R6c or S(O)2R6c; wherein R6c and RSD are each independently selected from hydrogen or (1 -3C)alkyl; wherein any (1 -3C)alkyl, (2-3C)alkenyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl present in a substituent on group Z, including those in R6c and RSD, is optionally further substituted by one or more substituents selected from halo, cyano, oxo, (1-3C)alkyl, (1-3C)haloalkyl, NRSERSF, ORSE, C(O)R6E, C(O)OR6E or OC(O)R6E; wherein RSE and RSF are each independently selected from hydrogen or (1 -3C)alkyl; wherein R6Nand R7Nare each independently selected from (1 -4C)alkyl which is optionally substituted by one or more substituents selected from halo, cyano, oxo, (3- 6C)cycloalkyl, 4- to 7-membered heterocyclyl, NRSGRSH, ORSG, C(O)RSG, C(O)OR6G, C(O)N(R6H)R6G, N(R6H)C(O)R6G, SR6G, S(O)RSG or S(O)2R6G; wherein R6G and R6H are each independently selected from hydrogen or (1 -3C)alkyl.(107) Z is selected from(3-12C)cycloalkyl, a 4- to 12-membered heterocyclic ring (including fused, bridged and spirocyclic heterocyclic rings), phenyl, mono- or bicyclic heteroaryl or NR6NR7N; wherein any (3-12C)cycloalkyl, a 4- to 12-membered heterocyclic ring, phenyl or mono- or bicyclic heteroaryl ring may be optionally substituted by one or more substituents selected from halo, cyano, oxo, (1-3C)alkyl, (1-3C)alkenyl, (3-4C)cycloalkyl, 5-membered heteroaryl, NRBCRSD, =CR6cR6D, ORBC, C(O)RBC, C(O)ORBC, C(O)N(R6D)R6C,N(R6D)C(O)R6C, SR6c or S(O)2R6c; wherein R6c and RBD are each independently selected from hydrogen or (1-3C)alkyl; wherein any (1 -3C)alkyl, (1-3C)alkenyl, (3-4C)cycloalkyl, 5-membered heteroaryl, present in a substituent on group Z, including those in R6c and RBD, is optionally further substituted by one or more substituents selected from halo, cyano, oxo, NRBERSF, ORGE, C(O)RGE, C(O)ORBE or OC(O)RBE; wherein RGE and RGF are each independently selected from hydrogen or (1 -3C)alkyl; wherein R6Nand R7Nare each independently selected from (1 -4C)alkyl which is optionally substituted by one or more substituents selected from halo, cyano, oxo, (3- 6C)cycloalkyl, 4- to 7-membered heterocyclyl, NRGGR6H, ORGG, C(O)RGG, C(O)ORBG, C(O)N(R6H)R6G or N(R6H)C(O)R6G; wherein R6c and Ren are each independently selected from hydrogen or (1 -2C)alkyl.(108) Z is selected from (3-8C)cycloalkyl, a 4- to 12-membered nitrogen linked heterocyclic ring (including fused, bridged and spirocyclic heterocyclic rings), phenyl, mono- or bicyclic heteroaryl or NR6NR7N; wherein any (3-8C)cycloalkyl, 4- to 12-membered nitrogen linked heterocyclic ring, phenyl or mono- or bicyclic heteroaryl may be optionally substituted by one or more substituents selected from halo, cyano, oxo, (1-3C)alkyl, (3-4C)cycloalkyl, 5-membered heteroaryl, NRSCRSD, =CR6CR6D, OR6c, C(O)R6c, C(O)OR6c, C(O)N(RBD)R6C, N(RBD)C(O)RBC, SR6c or S(O)2R6c; wherein R6c and RBD are each independently selected from hydrogen or (1- 3C)alkyl; wherein any (1 -3C)alkyl, (3-4C)cycloalkyl or 5-membered heteroaryl present substituent on group Z, including those in R6c and RBD, is optionally further substituted by one or more substituents selected from halo, cyano, oxo, NRBERSF, ORGE, C(O)RGE, C(O)ORGE or OC(O)RGE; wherein RGE and RBF are each independently selected from hydrogen or (1- 3C)alkyl; wherein R6Nand R7Nare each independently selected from (1 -4C)alkyl which is optionally substituted by one or more substituents selected from halo, cyano, oxo, (3-6C)cycloalkyl, NRSGRSH, ORSG or C(0)R6G; wherein R6c and RSH are each independently selected from hydrogen or (1 -2C)alkyl.(109) Z is selected from (3-8C)cycloalkyl, 5- to 12-membered nitrogen linked mono- or bicyclic heterocyclic ring (including fused, bridged and spirocyclic heterocyclic rings), phenyl, mono- or bicyclic heteroaryl or NR6NR7N; wherein any (3-8C)cycloalkyl, a 5- to 12-membered nitrogen linked mono- or bicyclic heterocyclic ring (including fused, bridged and spirocyclic heterocyclic rings), phenyl or mono- or bicyclic heteroaryl may be optionally substituted by one or more substituents selected from halo, cyano, oxo, (1-3C)alkyl, (1-3C)alkenyl, (3-4C)cycloalkyl, 5-membered heteroaryl, NR6CR6D, =CR6cR6D, OR6c, SR6c or S(O)2R6c; wherein R6c and R6D are independently selected from hydrogen or methyl; wherein any (1 -3C)alkyl substituent on group Z, including R6c and RSD, is optionally further substituted by one or more substituents selected from halo, cyano, oxo, NRSERSF or ORSE; wherein RSE and RSF are each independently selected from hydrogen or (1 -2C)alkyl; wherein R6Nand R7Nare each independently selected from (1 -4C)alkyl which is optionally substituted by (3-4C)cycloalkyl.(110) Z is selected from (3-7C)cycloalkyl, 5- to 6-membered nitrogen linked monocyclic saturated or partially saturated heterocyclyl, 4- to 10-membered nitrogen linked fused bicyclic heterocyclyl (including saturated or partially saturated ring systems), 4- to 10- membered nitrogen linked spirocyclic bicyclic heterocyclyl, phenyl, mono- or bicyclic heteroaryl mono- or bicyclic heteroaryl (including partially aromatic heteroaryl, e.g. a 4- to 10-membered nitrogen linked heterocylic ring fused to an aromatic or heteroaromatic ring) or NR6NR7Nwherein any (3-7C)cycloalkyl, 5- to 6-membered nitrogen linked monocyclic saturated or partially saturated heterocyclyl, 4- to 10-membered nitrogen linked fused bicyclic heterocyclyl, 4- to 10-membered nitrogen linked spirocyclic bicyclic heterocyclyl, 4- to 10-membered nitrogen linked fused bicyclic heterocylic ring comprising a non-aromatic heterocyclic ring fused to an aromatic or heteroaromatic ring, phenyl or mono- or bicyclic heteroaryl, may be optionally substituted by one or more substituents selected from halo, cyano, oxo, methyl, =CH2, cyclopropyl, 5-membered heteroaryl, NH2, methoxy, hydroxymethyl, OH, fluoromethoxy, fluoromethyl (e.g. CF3, CHF2 or CH2F), S-CH3 or S(O)2CH3; wherein R6Nis (1 -2C)alkyl and R7Nis (1 -2C)alkyl which is optionally substituted by (3- 4C)cycloalkyl.(111) Z is selected from 5- to 6-membered monocyclic heterocyclyl, a 4- to 10-membered nitrogen linked fused bicyclic heterocylic ring which comprises a non-aromatic heterocyclic ring fused to an aromatic or heteroaromatic ring, phenyl or NR6NR7N; wherein the 5- to 6-membered monocyclic heterocyclyl or 4- to 10-membered fused bicyclic ring comprising a non-aromatic ring fused to an aromatic ring may be optionally substituted by one or more substituents selected from fluoro, chloro, cyano, oxo, methyl, =CH2, NH2, methoxy, hydroxy(1-2C) alkyl, OH, fluoromethoxy, fluoromethyl (e.g. CF3, CHF2or CH2F) or S-CH3; wherein R6Nis (1 -2C)alkyl and R7Nis (1 -2C)alkyl which is optionally substituted by(3-4C)cycloalkyl.(112) Z has a structure selected from:wherein any of the group Z rings above may be substituted on an available carbon atom by one or more substituents as defined in any one of the preceding claims; and R6Nand R7Nare as defined anywhere herein;are selected from hydrogen or (1- 2C)alkyl;(113) Z has a structure selected from:wherein the group Z rings above may be substituted on an available carbon atom by one or more substituents selected from halo, cyano, oxo, (1-3C)alkyl, =CR6cR6D, (2-3C)alkenyl, (3- 6C)cycloalkyl, 5-membered heteroaryl, (1-3C)haloalkyl, NRSCRSD, OR6c, SR6c, S(O)R6c or S(O)2R6c; wherein R6c is selected from hydrogen or (1 -2C)alkyl;wherein any (1 -3C)alkyl substituent on a ring above is optionally further substituted by one or more substituents selected from halo, cyano, oxo, (1 -3C)alkyl, (1-3C)haloalkyl, are each independently selected from hydrogen ormethyl; R6Nand R7Nare each independently selected from (1 -4C)alkyl which is optionally substituted by (3-4C)cycloalkylare selected from hydrogen, (1 -2C)alkyl or a prodrug moiety, e.g. a prodrug moeity of the formula:(114) Z has a structure selected from:wherein the group Z rings above may be substituted on an available carbon atom by one or more substituents selected from halo, cyano, (1 -3C)alkyl, (1-3C)haloalkyl or OR6c; wherein R6c is selected from hydrogen or (1 -2C)alkyl; and selected from hydrogen, (1 -2C)alkyl or a prodrug moiety, e.g. aprodrug moeity of the formula.(115) Z has a structure selected from:wherein the group Z rings above may be substituted on an available carbon atom by one or more substituents selected from halo, cyano, (1 -3C)alkyl, (1-3C)haloalkyl or OR6c; wherein R6c is selected from hydrogen or (1 -2C)alkyl; and selected from hydrogen or (1 -2C)alkyl.(116) Z has a structure selected from:wherein R100, R101, R102 and R103 are each selected from hydrogen, methyl, fluoromethyl, methoxy, fluoro or chloro;R104 is selected from hydrogen or methyl;R105 is selected from hydrogen or hydroxy;RZ3, RZ5, RZ12, Rz13 and RZ144ar seelected from hydrogen, methyl, or a prodrug moiety of the formula:(117) Z has a structure selected from:wherein R1co, R101, R102, R103 and R104 are each selected from hydrogen, fluoro or methyl;Rzs, Rzn and Rzu are selected from hydrogen or a prodrug moiety of the formula:wherein R103 is hydrogen or methyl; Rzn is selected from hydrogen or a prodrug moiety of the formula:(119) R4pis selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F) or OMe.(120) R4pis selected from hydrogen, fluoro, chloro or methyl.(121) R4pis selected from hydrogen or fluoro;(122) Rsp is selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 orCH2F), fluoromethoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe.(123) R8Pis selected from hydrogen, fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2or OMe.(124) R8Pis hydrogen.(125) RePis selected from hydrogen, halo, methyl, or NH2.(126) RePis selected from hydrogen, halo (e.g. fluoro or chlro) or NH2.(127) RePis selected from hydrogen or chlro.(128) R7Pis selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 orCH2F), fluoromethoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe.(129) R7Pis selected from hydrogen, fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2or OMe.(130) R7Pis hydrogen.(131) RePis selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F) or OMe.(132) RePis selected from hydrogen, fluoro, chloro, methyl or OMe;(133) RePis selected from hydrogen or methoxy.(134) R29, R30, R31 and R32 are each independently selected from hydrogen, halo, cyano, (1-3C)alkyl, (3-6C)cycloalkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1- 3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.(135) R29, R30, R31 and R32 are each independently selected from hydrogen, halo, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2 or OCH2F), NH2, OMe or OH.(136) R29, R30, R31 and R32 are each independently selected from hydrogen, halo or methyl.(137) R29, R30, R31 and R32 are each hydrogen.(138) Rzi, RZ2, RZS, RZ4, RZS, Rze, RZ?, RZS, Rzg, RZW, RZI 1 , Rzi2, Rzn and Rzu are selected from hydrogen, (1-2C)alkyl or a prodrug moiety, e.g. a prodrug moeity of the formula:(139) Rzi, Rzz, RZS, RZ4, RZS, Rze, RZ7, RZS, Rzg, RZW, RZI 1 , Rzi2, Rzn and Rzu are selected from hydrogen, methyl or a prodrug moiety, e.g. a prodrug moeity of the formula:(140) Rzi, RZ2, RZS, RZ4, RZS, Rze, RZ?, RZS, Rzg, RZW, RZI 1 , Rzi2, Rzn and Rzu are selected from hydrogen or methyl.(141) Rzi, RZ2, RZS, RZ4, RZS, Rze, RZ7, RZS, Rzg, RZW, RZI 1 , Rzi2, Rzn and Rzu are hydrogen.

[0086] Suitably, LA is as defined in any one of paragraphs (1) to (3) above. More suitably, LA is as defined in paragraph (2) or (3) above. Most suitably, LA is as defined in paragraph (3) above.

[0087] Suitably, Ri is as defined in any one of paragraphs (4) to (15) above. Suitably, Ri is as defined in any one of paragraphs (10) to (15) above. More suitably, Ri is as defined in any one of paragraphs (13) to (15) above. Most suitably, Ri is as defined in paragraph (14) or (15) above.

[0088] Suitably, RI N and RZN are as defined in paragraph (16) or (17) above. Most suitably,RIN and RZN are as defined in paragraph (16) above.

[0089] Suitably, R4 is as defined in any one of paragraphs (18) to (20) above. Most suitably,R4 is as defined in paragraph (20) above.

[0090] Suitably, R5 is as defined in any one of paragraphs (21) to (23) above. Most suitably,Rs is as defined in paragraph (23) above.

[0091] Suitably, Re is as defined in any one of paragraphs (24) to (26) above. Most suitably,Re is as defined in paragraph (25) or (26) above.

[0092] Suitably, R7 is as defined in any one of paragraphs (27) to (29) above. Most suitably,R7 is as defined in paragraph (29) above.

[0093] Suitably, Rs is as defined in any one of paragraphs (30) to (32) above. Most suitably,Rs is as defined in paragraph (32) above.

[0094] Suitably, R9is as defined in any one of paragraphs (33) to (36) above. More suitably,R9is as defined in paragraph (35) or (36) above. Most suitably, R9is as defined in paragraph (36) above.

[0095] Suitably, R10 is as defined in any one of paragraphs (37) to (40) above. More suitably, R10 is as defined in paragraph (39) or (40) above. Most suitably, R10 is as defined in paragraph (40) above.

[0096] Suitably, R11 is as defined in any one of paragraphs (41) to (44) above. More suitably, R11 is as defined in paragraph (43) or (44) above. Most suitably, R11 is as defined in paragraph (44) above.

[0097] Suitably, R1cis as defined in any one of paragraphs (45) to (47) above. Most suitably, R12 is as defined in paragraph (47) above.

[0098] Suitably, R13 is as defined in any one of paragraphs (48) to (50) above. Most suitably, R13 is as defined in paragraph (50) above.

[0099] Suitably, R14 is as defined in any one of paragraphs (51) to (53) above. Most suitably, R14 is as defined in paragraph (53) above.

[0100] Suitably, R1cis as defined in any one of paragraphs (54) to (56) above. Most suitably, R15 is as defined in paragraph (56) above.

[0101] Suitably, R1cis as defined in any one of paragraphs (57) to (59) above. Most suitably, R1cis as defined in paragraph (59) above.

[0102] Suitably, R17 is as defined in any one of paragraphs (60) to (62) above. Most suitably, R17 is as defined in paragraph (62) above.

[0103] Suitably, R1cis as defined in any one of paragraphs (63) to (65) above. Most suitably, R1 9s as defined in paragraph (65) above.

[0104] Suitably, R20 is as defined in any one of paragraphs (66) to (68) above. Most suitably, R20 is as defined in paragraph (68) above.

[0105] Suitably, R21 is as defined in any one of paragraphs (69) to (71) above. Most suitably, R21 is as defined in paragraph (71) above.

[0106] Suitably, R22 is as defined in any one of paragraphs (72) to (74) above. Most suitably, R22 is as defined in paragraph (74) above.

[0107] Suitably, R23 is as defined in any one of paragraphs (75) to (77) above. Most suitably, R23 is as defined in paragraph (77) above.

[0108] Suitably, R24 is as defined in any one of paragraphs (78) to (80) above. Most suitably, R24 is as defined in paragraph (80) above.

[0109] Suitably, R25 is as defined in any one of paragraphs (81) to (83) above. Most suitably, R25 is as defined in paragraph (83) above.

[0110] Suitably, R26 is as defined in any one of paragraphs (84) to (86) above. Most suitably, R26 is as defined in paragraph (86) above.

[0111] Suitably, R27 is as defined in any one of paragraphs (87) to (89) above. Most suitably, R27 is as defined in paragraph (89) above.

[0112] Suitably, R28 is as defined in any one of paragraphs (90) to (92) above. Most suitably, R27 is as defined in paragraph (92) above.

[0113] Suitably, Ring A is as defined in any one of paragraphs (93) to (99) above. More suitably, Ring A is as defined in any one of paragraphs (96) to (99) above. Most suitably, Ring A is as defined in paragraph (98) or (99) above.

[0114] Suitably, Ring A is as defined in any one of paragraphs (93) to (99a) above. More suitably, Ring A is as defined in any one of paragraphs (98a) to (99a) above. Most suitably, Ring A is as defined in paragraph (99) or (99a) above.

[0115] Suitably, Rsx and Rsyare as defined in any one of paragraphs (100) to (104) or (104a) above. More suitably, Rsx and Rsyare as defined in any one of paragraphs (102) to (104) or (104a) above. Most suitably, Rsx and Rsyare as defined in paragraph (104) or (104a) above.

[0116] Suitably, Z is as defined in any one of paragraphs (105) to (113) above. More suitably, Z is as defined in any one of paragraphs (109) to (113) above. Most suitably, Z is as defined in paragraph (111), (112) or (113) above.

[0117] Suitably, Z is as defined in any one of paragraphs (114) to (118) above. More suitably, Z is as defined in any one of paragraphs (115) to (118) above. Most suitably, Z is as defined in paragraph (117) or (118) above.

[0118] Suitably, R4Pis as defined in any one of paragraphs (119) to (121) above. Most suitably, R27 is as defined in paragraph (121) above.

[0119] Suitably, R8Pis as defined in any one of paragraphs (122) to (124) above. Most suitably, R27 is as defined in paragraph (124) above.

[0120] Suitably, RePis as defined in any one of paragraphs (125) to (127) above. Most suitably, R27 is as defined in paragraph (127) above.

[0121] Suitably, R7Pis as defined in any one of paragraphs (128) to (130) above. Most suitably, R27 is as defined in paragraph (130) above.

[0122] Suitably, R8Pis as defined in any one of paragraphs (131) to (133) above. Most suitably, R27 is as defined in paragraph (133) above.

[0123] Suitably, R29, R30, R31 and R32 are each independently as defined in any one of paragraphs (134) to (137). More suitably, R29, R30, R31 and R32 are each independently as defined in paragraph (136) or (137). Most suitably, R29, R30, R31 and R32 are each independently as defined in paragraph (137).

[0124] Rzi, RZ2, RZS, RZ4, RZS, Rze, RZ7, RZS, Rzg, RZW, RZI 1 , Rzi2, Rzn and Rzi4 are as defined in any one of (138) to (141). More suitably, Rzi, Rzz, Rzs, Rz4, Rzs, Rze, Rzz, Rzs, Rzg, Rzw, Rzn, Rzi2, Rzn and Rzu are as defined in paragraph (140) or (141). Most suitably, Rzi, Rzz, RZS, RZ4, RZS, Rze, RZ7, RZS, Rzg, RZW, RZI 1 , Rzi2, Rzn and Rzi4 are as defined in paragraph (141).

[0125] Suitably, Ri is a group with a formula selected from:wherein R4, Rs, Re, R7 and Rs are each independently as defined anywhere herein.

[0126] Suitably, Ri is a group with a formula selected from:wherein R4P, R5P, R6P, R7P, R8P, R9, R10, R11, R12, R13, R14and R15are each independently as defined anywhere herein.

[0127] Suitably, Ri is a group of the formula:wherein R4P, R5P, R6P, R7Pand R8Pare each independently as defined anywhere herein.

[0128] Suitably, Ri is a group with a formula selected from:wherein R9, R10 R11 , R12, R13, R14 and R15 are each independently as defined anywhere herein.

[0129] Suitably, Ri is a group with a formula selected from:wherein R23, R24, R25, R26, R27, R28, RIN and R2N are each independently as defined anywhere herein.

[0130] Suitably, R1 is a group with a formula selected from:wherein:Q1 is selected from C-R9or N; wherein R9is as defined anywhere herein;Q2 is selected from C-H or N;R11 and R13 are each independently as defined anywhere herein.

[0131] Suitably, Ri is a group with a formula selected fromwherein R9, R10, R11 , R12, R13, R14 and R15 are each independently as defined anywhere herein.

[0132] Suitably, R1 is a group with a formula selected from:wherein:R9is selected from hydrogen, methyl, fluoro or chloro;R11 is selected from hydrogen or NH2; andR13 is selected from hydrogen or methyl.wherein R4, Rs, Re and Rs are each independently as defined anywhere herein.

[0134] Suitably, R1 is:wherein R4, Rs and Re are each independently as defined anywhere herein.

[0135] Suitably, R1 is:wherein R4, Rs, Re and R7 are each independently as defined anywhere herein.

[0136] Suitably, R1 is:wherein R4, Rs, R7 and Rs are each independently as defined anywhere herein.

[0137] Suitably, R1 is:wherein R4p, R5p, R6p, R7Pand R8pare each independently as defined anywhere herein.

[0138] Suitably, R1 is:wherein R9, Rw, R11 , R12, R13, R14 and R1care each independently as defined anywhere herein.

[0139] Suitably, R1 is:wherein Rg, R10, R11 , R14 and R1care each independently as defined anywhere herein.

[0140] Suitably, R1 is:wherein R9, R1c, R11, R13, R14 and R 15 are each independently as defined anywhere herein.

[0141] Suitably, R1 is:wherein R10, R11, R13, R14 and R15 are each independently as defined anywhere herein.

[0142] Suitably, R1 is:wherein R9, R11 , R12, R13, R14 and R15 are each independently as defined anywhere herein.

[0143] Suitably, 1 is:wherein R9, R11, R13, R14 and R15 are each independently as defined anywhere herein.

[0144] Suitably, R1 is:wherein R9, R10, R11 , R12, R13 and R14 are each independently as defined anywhere herein.

[0145] Suitably, R1 is:wherein R9, R10, R11, R12, R14 and R15 are each independently as defined anywhere herein.

[0146] Suitably, R1 is:wherein R9, R10, R12, R13, R14 and R15 are each independently as defined anywhere herein.

[0147] Suitably, R1 is:wherein R9, R10, R11, R12, R13 and R15 are each independently as defined anywhere herein.

[0148] Suitably, R1 is:wherein R9, R10, R11 , R13 and R14 are each independently as defined anywhere herein.

[0149] Suitably, R1 is:wherein R1c, R17, R19, R20, R21 and R22 are each independently as defined anywhere herein.

[0150] Suitably, R1 is:wherein RIN, R23, R24, R25, R26 and R27 are each independently as defined anywhere herein.

[0151] Suitably, R1 is:wherein R23, R24, R25, R27 and R2s are each independently as defined anywhere herein.

[0152] Suitably, R1 is:wherein R23, R24, R25, R27 and R2s are each independently as defined anywhere herein.

[0153] Suitably, R1 is:wherein R2N, R23, R24, R25, R27 and R28 are each independently as defined anywhere herein.

[0154] Suitably, Ri is:wherein R2N, R23, R24, R25 and R28 are each independently as defined anywhere herein.

[0155] Suitably, R1 is:wherein R23, R24, R25 and R27 are each independently as defined anywhere herein.

[0156] Suitably, R1 is:wherein R23, R24, R25 and R27 are each independently as defined anywhere herein.

[0157] Suitably, R1 is:wherein R29, R30, R31 and R32 are each independently as defined anywhere herein.

[0158] Suitably, R1 is a group with a formula selected from:wherein R4, R5, Re, Rs, R4p, Rsp, Rep, R7p, Rsp, R9, R10, R11 , R12, R13, R14, R15, R23, R24, R25, R26, R27, R28, R29, R30, R31 and R32 are each independently as defined anywhere herein.

[0159] In a particular group of the compounds of the invention, the compounds have the structural formula (II) (a sub-definition of Formula (I)):wherein Ri, RXIN, X2, LA, RSX and Z each have any of the meanings as defined herein; or a pharmaceutically acceptable salt thereof.

[0160] In a particular group of the compounds of the invention, the compounds have the structural formula (la) (a sub-definition of Formula (I)):wherein R1, RXIN, RSX and Z each have any of the meanings as defined herein; or a pharmaceutically acceptable salt thereof.

[0161] In an embodiment of the compounds of Formula (la):R1 is as defined in any one of paragraphs (4) to (15) above;RXI N is as defined in any one of paragraphs (93) to (99);Rsx is as defined in any one of paragraphs (100) to (104) above; andZ is as defined in any one of paragraphs (85) to (92) above.

[0162] In an embodiment of the compounds of Formula (la):Ri is as defined in any one of paragraphs (10) to (15) above;RXI N is as defined in any one of paragraphs (95) to (99);Rsx is as defined in any one of paragraphs (102) to (104) or (104a) above; andZ is as defined in any one of paragraphs (88) to (92) above.

[0163] In an embodiment of the compounds of Formula (la):Ri is as defined in any one of paragraphs (13) to (15) above;RXI N is as defined in any one of paragraphs (95) to (99);Rsx is as defined in any one of paragraphs (103), (104) or (104a) above; andZ is as defined in paragraph (91) or (92) above.

[0164] In an embodiment of the compounds of Formula (la):Ri is as defined in paragraph (14) or (15) above;RXI N is as defined in paragraph (99);Rsx is as defined in paragraph (104) or (104a) above; andZ is as defined in paragraph (91) or (92) above.

[0165] In an embodiment of the compounds of Formula (la):Ri is as defined in any one of paragraphs (4) to (15) above;RXI N is as defined in any one of paragraphs (93) to (99);Rsx is as defined in any one of paragraphs (100) to (104) above; andZ is as defined in any one of paragraphs (114) to (118) above.

[0166] In an embodiment of the compounds of Formula (la):Ri is as defined in any one of paragraphs (10) to (15) above;RXI N is as defined in any one of paragraphs (95) to (99);Rsx is as defined in any one of paragraphs (102) to (104) or (104a) above; andZ is as defined in any one of paragraphs (115) to (118) above.

[0167] In an embodiment of the compounds of Formula (la):Ri is as defined in any one of paragraphs (13) to (15) above;RXI N is as defined in any one of paragraphs (95) to (99);Rsx is as defined in any one of paragraphs (103), (104) or (104a) above; andZ is as defined in paragraph (116), (117) or (118) above.

[0168] In an embodiment of the compounds of Formula (la):Ri is as defined in paragraph (14) or (15) above;RXI N is as defined in paragraph (99);Rsx is as defined in paragraph (104) or (104a) above; andZ is as defined in paragraph (117) or (118) above.

[0169] In a particular group of the compounds of the invention, Z is a carbon linked heteroaryl or aryl group. The carbon linked heteroaryl or aryl group may be any suitable group described herein, for example:wherein Rz and Rzu are as defined anywhere herein, and the rings above may be optionally substituted on an available carbon atom by one or more substitutents as described elsewhere herein.

[0170] In another particular group of the compounds of the invention, Z is a nitrogen- linked heterocyclic ring or a nitrogen-linked heteroaryl. The nitrogen linked heterocyclic ring or nitrogen linked heteroaryl group may be any suitable group described herein, for example:wherein Rzs is as defined herein, and the rings above may be optionally substituted on an available carbon atom by one or more substitutents as described elsewhere herein.

[0171] In certain compounds of the invention, Rsx is not hydrogen, methyl or ethyl.Preferably, in such compounds, Rsx is chloro.Particular Embodiments of the Invention

[0172] In an embodiment, the compounds have the structural formula (la) (a sub- definition of Formula (I)), or a pharmaceutically acceptable salt thereof:wherein:Ri is selected from:wherein:R4, Rs, Re, R7, Rsp, R9, R10, R11 , R12, R13, R14, R15, R23, R24, R25, R26, R27, R28, R29, R30, R31 and R32 are each independently as defined anywhere herein;RXI N is selected from methyl or ethyl, wherein the methyl and ethyl are optionally substituted by one or more fluoro substituents;Rsx is selected from methyl, ethyl or chloro, wherein methyl or ethyl are optionally substituted by one or more substituents selected from fluoro, hydroxy or NH2; andZ is a group as defined in paragraph (114) above.

[0173] In an embodiment, the compounds have the structural formula (la) (a sub- definition of Formula (I)), or a pharmaceutically acceptable salt thereof:wherein:wherein:R9, R1c, R11 , R12, R13, R and R15 are each independently as defined anywhere herein;RXI N is selected from methyl or ethyl, wherein the methyl and ethyl are optionally substituted by one or more fluoro substituents;Rsx is selected from chloro or methyl, wherein methyl is optionally substituted by one or more substituents selected from fluoro, hydroxy or NH2; and Z is as defined in paragraph (115) or (116).

[0174] In another embodiment, the compounds have the structural formula (la) (a sub- definition of Formula (I)), or a pharmaceutically acceptable salt thereof:wherein:Ri is selected from:wherein:R9is selected from hydrogen, methyl, fluoro or chloro; R11 is selected from hydrogen or NH2;R13 is selected from hydrogen or methyl;RXI N is selected from methyl or ethyl;Rsx is selected from chloro or methyl, wherein methyl is optionally substituted by one or more substituents selected from fluoro, hydroxy or NH2; andZ is as defined in paragraph (116) or (117).

[0175] In another embodiment, the compounds have the structural formula (lb) (a subdefinition of Formula (I)), or a pharmaceutically acceptable salt thereof:wherein Ri, RXIN, RSX and Z are as defined anywhere herein.

[0176] Suitably, in an embodiment of the compounds of Formula (lb): R103 is hydrogen or methyl;Rz is selected from hydrogen or a prodrug moiety of the formula:RXI N is selected from methyl or ethyl;Rsx is selected from chloro or methyl, wherein methyl is optionally substituted by one or more substituents selected from fluoro, hydroxy or NH2;R1 is as defined in any one of paragraphs (13) to (15) above.

[0177] In another embodiment, the compounds have the structural formula (Ic) (a subdefinition of Formula (I)), or a pharmaceutically acceptable salt thereof:wherein:Q1 is selected from C-R9or N; wherein R9is as defined anywhere herein; Q2 is selected from C-H or N;R11 , R13, RX1 N, R3X and Z are as defined anywhere herein.

[0178] Suitably, in an embodiment of the compounds of Formula (Ic):R9is selected from hydrogen, methyl, fluoro or chloro;R11 is selected from hydrogen or NH2; R13 is selected from hydrogen or methyl;RXI N is chloro;Rsx is selected from chloro or methyl, wherein methyl is optionally substituted by one or more substituents selected from fluoro, hydroxy or NH2;Z is as defined in paragraph (116) or (117).

[0179] Suitably, in an embodiment of the compounds of Formula (Ic):R9is selected from hydrogen, methyl, fluoro or chloro;R11 is selected from hydrogen or NH2;R13 is selected from hydrogen or methyl;RXI N is selected from methyl or ethyl;Rsx is selected from chloro or methyl, wherein methyl is optionally substituted by one or more substituents selected from fluoro, hydroxy or NH2;Z is as defined in paragraph (116) or (117).

[0180] Suitably, in an embodiment of the compounds of Formula (Ic):R9is selected from fluoro or chloro;R11 is hydrogen;R13 is selected from hydrogen or methyl;RXI N is methyl;Rsx is selected from chloro or methyl;Z is as defined in paragraph (118).

[0181] Suitably, a heteroaryl or heterocyclyl group as defined herein is a monocyclic or bicyclic heteroaryl or heterocyclyl group comprising one, two or three heteroatoms selected from N, O or S.

[0182] Suitably, a heteroaryl is a 5- or 6-membered heteroaryl ring comprising one, two or three heteroatoms selected from N, O or S.

[0183] Suitably, a heterocyclyl group is a 4-, 5- or 6-membered monocyclic heterocyclyl ring comprising one, two or three heteroatoms selected from N, O or S or a 5- to 10-membered biccyclic heterocyclyl ring (e.g. fused, bridged or spirocyclic) comprising one, two or three heteroatoms selected from N, O or S. Most suitably, a heterocyclyl group is a 5- or 6- membered ring comprising one, two or three heteroatoms selected from N, O or S [e.g. morpholinyl (e.g. 4-morpholinyl), oxetane, methyloxetane (e.g. 3-methyloxetane), pyrrolidinone (e.g. pyrrolidin-2-one)].

[0184] Suitably, an aryl group is phenyl.

[0185] Particular compounds of the present invention include any of the compounds exemplified in the present application, or a pharmaceutically acceptable salt or solvate thereof, and, in particular, any of the following:4-(3-azabicyclo[3.1 ,0]hexan-3-ylsulfonyl)-1 ,5-dimethyl-N-(5-quinolylmethyl)pyrrole-2- carboxamide;4-[[3-(hydroxymethyl)-1-piperidyl]sulfonyl]-1,5-dimethyl-N-(5-quinolylmethyl)pyrrole-2- carboxamide;4-(azepan-1-ylsulfonyl)-1 ,5-dimethyl-N-(2-methylbenzyl)-1 H-pyrrole-2-carboxamide;4-((3-azabicyclo[4.1 ,0]heptan-3-yl)sulfonyl)-1 ,5-dimethyl-N-(2-methylbenzyl)-1 H-pyrrole-2- carboxamide;4-((3,4-dihydroisoquinolin-2(1 H)-yl)sulfonyl)-1 ,5-dimethyl-N-(2-methylbenzyl)-1 H-pyrrole-2- carboxamide;4-((4-hydroxypiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(2-methylbenzyl)-1 H-pyrrole-2- carboxamide;5-bromo-1-methyl-4-[(4-methyl-1-piperidyl)sulfonyl]-N-(5-quinolylmethyl)pyrrole-2- carboxamide;5-cyano-1-methyl-4-[(4-methyl-1-piperidyl)sulfonyl]-N-(5-quinolylmethyl)pyrrole-2- carboxamide;5-cyclopropyl-1-methyl-4-[(4-methyl-1-piperidyl)sulfonyl]-N-(5-quinolylmethyl)pyrrole-2- carboxamide;1.5-dimethyl-4-[(4-methyl-1-piperidyl)sulfonyl]-N-(4-quinolylmethyl)pyrrole-2-carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(naphthalen-1-ylmethyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-[(4-methyl-1-piperidyl)sulfonyl]-N-(8-quinolylmethyl)pyrrole-2-carboxamide;N-(5-isoquinolylmethyl)-1 ,5-dimethyl-4-[(4-methyl-1-piperidyl)sulfonyl]pyrrole-2-carboxamide;N-(4-isoquinolylmethyl)-1 ,5-dimethyl-4-[(4-methyl-1-piperidyl)sulfonyl]pyrrole-2-carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;N-((1 H-indol-7-yl)methyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-((3-methylpyridin-4-yl)methyl)-1 H-pyrrole-2-carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(2-(trifluoromethoxy)benzyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-((4-methylpyridin-3-yl)methyl)-1 H-pyrrole- 2-carboxamide;1.5-dimethyl-N-((1-methyl-1 H-indol-4-yl)methyl)-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(quinoxalin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(pyrazolo[1 ,5-a]pyridin-4-ylmethyl)-1 H- pyrrole-2-carboxamide;N-(2-fluoro-6-methoxybenzyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;N-(3-amino-2-chlorobenzyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl) sulfonyl)- 1 H-pyrrole-2- carboxamide;4-[(4-hydroxypiperidin-1-yl)sulfonyl]-1 ,5-dimethyl-N-[(quinoline-5-yl)methyl]-1 H-pyrrole-2- carboxamide;1.5-dimethyl-N-[(quinoline-5-yl)methyl]-4-(1 ,2,3,4-tetrahydroisoquinoline-2-sulfonyl)-1 H- pyrrole-2-carboxamide;1.5-dimethyl-N-[(quinoline-5-yl)methyl]-4-{[4-(trifluoromethyl)piperidin-1-yl]sulfonyl}-1H- pyrrole-2-carboxamide;1.5-dimethyl-4-[(4-methylpiperidin-1-yl)sulfonyl]-N-[(quinolin-6-yl)methyl]-1H-pyrrole-2- carboxamide;4-(2,3-dihydro-1H-indole-1-sulfonyl)-1,5-dimethyl-N-[(quinolin-5-yl)methyl]-1H-pyrrole-2- carboxamide; give 4-[[4-(hydroxymethyl)-1-piperidyl]sulfonyl]-1,5-dimethyl-N-(6-quinolylmethyl)pyrrole-2- carboxamide;4-(3,4-dihydro-1H-2,6-naphthyridin-2-ylsulfonyl)-1,5-dimethyl-N-(5-quinolylmethyl)pyrrole-2- carboxamide;4-(6-azaspiro[3.4]octan-6-ylsulfonyl)-1,5-dimethyl-N-(5-quinolylmethyl)pyrrole-2- carboxamide;4-(3,4-dihydro-1 H-pyrrolo[1 ,2-a]pyrazin-2-ylsulfonyl)-1 ,5-dimethyl-N-(5- quinolylmethyl)pyrrole-2-carboxamide;4-(3,4-dihydro-1H-2,7-naphthyridin-2-ylsulfonyl)-1,5-dimethyl-N-(5-quinolylmethyl)pyrrole-2- carboxamide;1.5-dimethyl-4-(3-methylpyrrolidin-1-yl)sulfonyl-N-(5-quinolylmethyl)pyrrole-2-carboxamide;1.5-dimethyl-4-morpholinosulfonyl-N-(5-quinolylmethyl)pyrrole-2-carboxamide;4-[(4-fluoro-1-piperidyl)sulfonyl]-1,5-dimethyl-N-(5-quinolylmethyl)pyrrole-2-carboxamide;4-(((3S,4S)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)- 1 H-pyrrole-2-carboxamide;4-{[(3R,4R)-4-hydroxy-3-methylpiperidin-1-yl]sulfonyl}-1 ,5-dimethyl-N-[(quinolin-5-yl)methyl]-1 H-pyrrole-2-carboxamide;4-(((3S,4R)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide4-{[(3R,4S)-4-hydroxy-3-methylpiperidin-1-yl]sulfonyl}-1,5-dimethyl-N-[(quinolin-5-yl)methyl]-1 H-pyrrole-2-carboxamide;4-[(7-hydroxy-3,4-dihydro-1H-isoquinolin-2-yl)sulfonyl]-1 ,5-dimethyl-N-(5- quinolylmethyl)pyrrole-2-carboxamide;1.5-dimethyl-N-(5-quinolylmethyl)-4-(1 ,4,6,7-tetrahydropyrrolo[3,2-c]pyridin-5- ylsulfonyl)pyrrole-2-carboxamide;4-((6,7-dihydroisoxazolo[4,5-b]pyridin-4(5H)-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-((5-fluoroisoindolin-2-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;4-(isoindolin-2-ylsulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1H-pyrrole-2-carboxamide;4-(((3S,4S)-3-fluoro-4-methylpiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1H- pyrrole-2-carboxamide;4-(((3R,4R)-3-fluoro-4-methylpiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1H- pyrrole-2-carboxamide;1.5-dimethyl-4-((4-methyl-3,6-dihydropyridin-1 (2H)-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;1-ethyl-5-methyl-N-(2-methylbenzyl)-4-((4-methylpiperidin-1-yl)sulfonyl)-1H-pyrrole-2- carboxamide;N-((7-aminoquinazolin-5-yl)methyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H- pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-(2-chloro-6-methoxybenzyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;N-(2-methoxy-6-methylbenzyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-((6-methylquinolin-5-yl)methyl)-1H- pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-(benzo[d]thiazol-7-ylmethyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H-pyrrole-2- carboxamide;N-(2-chloro-6-(trifluoromethoxy)benzyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H- pyrrole-2-carboxamide;N-((4-aminonaphthalen-1-yl)methyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;N-(5-amino-2-chlorobenzyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;4-((4-hydroxypiperidin-1-yl)sulfonyl)-N-(2-methoxy-6-(trifluoromethyl)benzyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-4-((4-hydroxypiperidin-1-yl)sulfonyl)-1,5-dimethyl-1H- pyrrole-2-carboxamide;N-(2-chloro-6-(difluoromethoxy)benzyl)-4-((4-hydroxypiperidin-1-yl)sulfonyl)-1,5-dimethyl-1H- pyrrole-2-carboxamide;5-chloro-1-methyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;(S)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(1-(quinolin-5-yl)ethyl)-1 H-pyrrole-2- carboxamide;(R)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(1-(quinolin-5-yl)ethyl)-1 H-pyrrole-2- carboxamide;N-((6-chloroquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((4-methyl-3-oxopiperazin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;N-((8-hydroxyquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-(3-amino-2-methylbenzyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;N-(3-amino-2-methoxybenzyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-((4-methylcyclohexyl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((1 ,4,6,7-tetrahydro-5H-pyrazolo[4,3- c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-(2-fluoro-6-methoxybenzyl)-1 ,5-dimethyl-4-((1 ,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-1 ,5-dimethyl-4-((1 ,4,6,7-tetrahydro-5H- pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-1 ,5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-1 H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-1.5-dimethyl-1 H-pyrrole-2-carboxamide;4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-N-(2-fluoro-6-methoxybenzyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;4-(6,7-dihydro-4H-pyrazolo[1 ,5-a]pyrazin-5-ylsulfonyl)-N-[(6-fluoroquinoxalin-5-yl)methyl]-1.5-dimethyl-pyrrole-2-carboxamide;N-[(2-amino-3-methyl-4-pyridyl)methyl]-4-(6,7-dihydro-4H-pyrazolo[1 ,5-a]pyrazin-5- ylsulfonyl)-1 ,5-dimethyl-pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-4-((6,7-dihydropyrazolo[1,5-a]pyrazin-5(4H)-yl)sulfonyl)-1 ,5-dimethyl-1 H- pyrrole-2-carboxamide;4-((3,4-dihydro-2,6-naphthyridin-2(1H)-yl)sulfonyl)-1,5-dimethyl-N-((2-methylquinazolin-5- yl)methyl)-1 H-pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-4-((3,4-dihydro-2,6-naphthyridin-2(1 H)-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;5-chloro-4-((6,7-dihydropyrazolo[1,5-a]pyrazin-5(4H)-yl)sulfonyl)-N-(2-fluoro-6- methoxybenzyl)-1-methyl-1 H-pyrrole-2-carboxamide;5-chloro-4-(6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-ylsulfonyl)-N-[(6- fluoro- 5- quinolyl)methyl]-1-methyl-pyrrole-2-carboxamide;5-chloro-N-((6-fluoroquinolin-5-yl)methyl)-4-((4-hydroxypiperidin-1-yl)sulfonyl)-1-methyl-1 H- pyrrole-2-carboxamide;5-chloro-4-(2,3-dihydropyrrolo[3,2-b]pyridin-1-ylsulfonyl)-N-[(6-fluoro-5-quinolyl)methyl]-1- methyl-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-1,5-dimethyl-4-(phenylsulfonyl)-1H-pyrrole-2- carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-4-((4-chlorophenyl)sulfonyl)-1,5-dimethyl-1H- pyrrole-2-carboxamide;4-((3,4-dihydroisoquinolin-2(1 H)-yl)sulfonyl)-N-(imidazo[1 ,2-a]pyridin-5-ylmethyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-4-((3,4-dihydroisoquinolin-2(1H)-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-4-((7-fluoro-3,4-dihydroisoquinolin-2(1H)- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;4-((3-hydroxy-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((TRANS)-3,4-dimethylpyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;4-((5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((3S,4S)-3-fluoro-4-methylpyrrolidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;4-(((3R,4R)-3-fluoro-4-methylpyrrolidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;(R)-1,5-dimethyl-4-((3-methylpiperidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-((3-methylenepyrrolidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;(R)-4-((3,3-difluoro-4-methylpyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;(S)-4-((3,3-difluoro-4-methylpyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;1.5-dimethyl-4-((3-(methylthio)azetidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;(S)-1 ,5-dimethyl-4-((3-methylpiperidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;4-(((3S,4R)-3-fluoro-4-hydroxypiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((3R,4S)-3-fluoro-4-hydroxypiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((1 R,5R)-1 -cyano- 3-azabicyclo[3.1.0]hexan-3-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5- ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((1S,5S)-1-cyano-3-azabicyclo[3.1.0]hexan-3-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5- ylmethyl)-1 H-pyrrole-2-carboxamide;4-((6,7-dihydro-[1 ,2,3]triazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5- ylmethyl)-1 H-pyrrole-2-carboxamide;1.5-dimethyl-4-((2-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;(S)-4-((3-cyclopropylpyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole- 2-carboxamide;(R)-4-((3-cyclopropylpyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-((2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;(R)-1 ,5-dimethyl-4-((3-(methylsulfonyl)pyrrolidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;1.5-dimethyl-N-(quinolin-5-ylmethyl)-4-((2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5- yl)sulfonyl)-1 H-pyrrole-2-carboxamide;(R)-4-((3-(1 H-pyrazol-4-yl)pyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;(S)-4-((3-(1 H-pyrazol-4-yl)pyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;4-((3,3-difluoropiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;4-((6-hydroxy-3-azabicyclo[3.1 ,0]hexan-3-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;1.5-dimethyl-4-((3-methyl-2,5-dihydro-1 H-pyrrol-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;4-(((3S,4R)-3-methoxy-4-methylpiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)- 1 H-pyrrole-2-carboxamide;4-(((3R,4S)-3-methoxy-4-methylpiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;(S)-1,5-dimethyl-4-((7-methyl-6,7-dihydropyrazolo[1,5-a]pyrazin-5(4H)-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((2R,4S)-4-hydroxy-2-methylpyrrolidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;(S)-4-((8-hydroxy-5-azaspiro[2.5]octan-5-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;(R)-4-((8-hydroxy-5-azaspiro[2.5]octan-5-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;1.5-dimethyl-4-((3-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;1.5-dimethyl-N-(quinolin-5-ylmethyl)-4-((3-(trifluoromethyl)-2,5-dihydro-1H-pyrrol-1- yl)sulfonyl)-1H-pyrrole-2-carboxamide;4-((7,7-difluoro-3-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-1,5- dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-((6-(hydroxymethyl)-3-azabicyclo[3.1.0]hexan-3-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5- ylmethyl)-1H-pyrrole-2-carboxamide;4-(((3S,4S)-3-fluoro-4-hydroxypiperidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((S)-3-((R)-1-hydroxyethyl)pyrrolidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((S)-3-((S)-1-hydroxyethyl)pyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((R)-3-((S)-1-hydroxyethyl)pyrrolidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((R)-3-((R)-1-hydroxyethyl)pyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-((2,3-dihydro-1 H-pyrrolo[3,2-b]pyridin-1 -yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-((2,3-dihydro-1 H-pyrrolo[3,2-b]pyridin-1-yl)sulfonyl)-1 ,5-dimethyl-N-((2-methylquinazolin-5- yl)methyl)-1 H-pyrrole-2-carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-4-((4-hydroxypiperidin-1-yl)sulfonyl)-1,5-dimethyl-1 H- pyrrole-2-carboxamide;N-((6-fluoroquinoxalin-5-yl)methyl)-4-((4-hydroxypiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-1 H- pyrrole-2-carboxamide;N-(2-(difluoromethyl)-6-methoxybenzyl)-4-((4-hydroxypiperidin-1-yl)sulfonyl)-1,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-4-((4-(difluoromethyl)piperidin-1-yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((6-chloroquinoxalin-5-yl)methyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H- pyrrole-2-carboxamide;1,5-dimethyl-N-((3-methylcinnolin-5-yl)methyl)-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;N-((1 ,6-naphthyridin-5-yl)methyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;4-((1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-4-((1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((6-amino-3-fluoropyridin-2-yl)methyl)-4-((1,3-dihydro-2H-pyrrolo[3,4c]pyridin-2- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((5-amino-3-fluoropyridin-2-yl)methyl)-4-((1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((1 H-indazol-4-yl)methyl)-4-((1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)sulfonyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;(S)-N-(2-fluoro-6-methoxybenzyl)-1,5-dimethyl-4-((3-methyl-5-oxopiperazin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;4-((7,8-dihydropyrido[3,4-d]pyridazin-6(5H)-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-1,5-dimethyl-4-((3-methyl-5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-4-((5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-1,5-dimethyl-4-((1,5,6,7-tetrahydro-4H-pyrazolo[4,3- b]pyridin-4-yl)sulfonyl)-1H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-1,5-dimethyl-4-((3-oxopiperazin-1-yl)sulfonyl)-1H-pyrrole-2- carboxamide;4-((3-aminopiperidin-1-yl)sulfonyl)-N-((6-chloroquinolin-5-yl)methyl)-1,5-dimethyl-1H-pyrrole-2-carboxamide;4-((4H-thieno[3,4-c]pyrrol-5(6H)-yl)sulfonyl)-N-((8-aminoquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-4-((6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-1,5-dimethyl-4-((4-methyl-3,6-dihydropyridin-1(2H)- yl)sulfonyl)-1H-pyrrole-2-carboxamide;4-((5,6-dihydropyrrolo[3,2-c]pyrazol-4(1H)-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;4-((5,6-dihydropyrrolo[3,2-c]pyrazol-4(1H)-yl)sulfonyl)-N-(2-fluoro-6-methoxybenzyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;4-((2,3-dihydro-1 H-pyrido[2,3-b][1 ,4]oxazin-1-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;(R)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((2-methylmorpholino)sulfonyl)-1H- pyrrole-2-carboxamide;(S)-N-((6-fluoroquinolin-5-yl)methyl)-1,5-dimethyl-4-((2-methylmorpholino)sulfonyl)-1H- pyrrole-2-carboxamide;4-(dimethylsulfamoyl)-N-[(6-fluoro-5-quinolyl)methyl]-1 ,5-dimethyl-pyrrole-2-carboxamide;N-[(6-fluoro-5-quinolyl)methyl]-1,5-dimethyl-4-[(3S)-3-methylpiperazin-1-yl]sulfonyl-pyrrole-2- carboxamide;4-(((3R,4S)-3-amino-4-methylpiperidin-1-yl)sulfonyl)-N-(2-fluoro-6-methoxybenzyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-4-(((3r,4r)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-4-(((3S,4S)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-(2-fluoro-6-methoxybenzyl)-4-(((3r,4r)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-(2-fluoro-6-methoxybenzyl)-4-(((3S,4S)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-4-((3,4-dihydro-2,6-naphthyridin-2(1 H)-yl)sulfonyl)-5- methyl-1H-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-4-((6,7-dihydrothieno[3,2-c]pyridin-5(4H)- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;4-((4-chlorophenyl)sulfonyl)-N-((6-fluoroquinoxalin-5-yl)methyl)-1,5-dimethyl-1H-pyrrole-2- carboxamide;4-((4-chlorophenyl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1H-pyrrole-2- carboxamide;1.5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-4-((1,4,6,7-tetrahydro-5H-pyrazolo[4,3- c]pyridin-5-yl)sulfonyl)-1H-pyrrole-2-carboxamide;4-((5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)sulfonyl)-1,5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-1H-pyrrole-2-carboxamide;4-((4,6-dihydropyrrolo[3,4-c]pyrazol-5(1H)-yl)sulfonyl)-1 ,5-dimethyl-N-((2-methylquinazolin-5- yl)methyl)-1 H-pyrrole-2-carboxamide;4-((6,7-dihydro-[1 ,2, 3]triazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-1 ,5-dimethyl-N-((2- methylquinazolin-5-yl)methyl)-1H-pyrrole-2-carboxamide;1.5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-4-((3,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((3,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5- c]pyridin-5-yl)sulfonyl)-1H-pyrrole-2-carboxamide;4-((5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-5-chloro-1-methyl-4-((1,4,6,7-tetrahydro-5H- pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-4-(((3S,4R)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;4-((6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-5- methyl-1H-pyrrole-2-carboxamide;4-((2,3-dihydro-1 H-imidazo[1,2-b]pyrazol-1-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;4-(((3R,4R)-3-fluoro-4-hydroxypiperidin-1-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;4-((2-oxa-5-azabicyclo[4.1 ,0]heptan-5-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;4-((3-azabicyclo[3.1 ,0]hexan-3-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H- pyrrole-2-carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-4-(pyrrolidin-1-ylsulfonyl)-1H-pyrrole-2- carboxamide;4-(azetidin-1 -ylsulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H-pyrrole-2- carboxamide;4-((1H-pyrrolo[3,2-b]pyridin-1-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1,5-dimethyl-1H- pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-4-((4,6-dihydro-5H-thieno[2,3-c]pyrrol-5-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((8-amino-6-fluoroquinolin-5-yl)methyl)-4-((6,7-dihydropyrazolo[1,5-a]pyrazin-5(4H)- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((8-amino-6-fluoroquinolin-5-yl)methyl)-1,5-dimethyl-4-((1,4,6,7-tetrahydro-5H- pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-((8-amino-6-fluoroquinoxalin-5-yl)methyl)-1,5-dimethyl-4-((1 ,4,6,7-tetrahydro-5H- pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;4-((1H-pyrrol-1-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1,5-dimethyl-1H-pyrrole-2- carboxamide;4-((3-chloro-1 H-pyrrol-1-yl) sulfonyl)-N-((6-fluoroquinolin-5-yl) methyl)-"!, 5-dimethyl-1H- pyrrole-2-carboxamide;4-((2-chloro-1 H-pyrrol-1-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H- pyrrole-2-carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-5-methyl-4-((2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5- yl)sulfonyl)-1-(2,2,2-trifluoroethyl)-1H-pyrrole-2-carboxamide;N-((8-aminoisoquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H- pyrrole-2-carboxamide; and4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-N-(2-fluoro-6-methoxybenzyl)-1,5- dimethyl-1 H-imidazole-2-carboxamide;N-((6-fluoroquinazolin-5-yl)methyl)-1,5-dimethyl-4-((1,4,6,7-tetrahydro-5H-pyrazolo[4,3- c]pyridin-5-yl)sulfonyl)-1H-pyrrole-2-carboxamide;N-(1 ,3-benzothiazol-4-ylmethyl)-1 ,5-dimethyl-4-(1 ,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5- ylsulfonyl)pyrrole-2-carboxamide;N-(benzo[d]thiazol-7-ylmethyl)-1,5-dimethyl-4-((1 ,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;4-(4-chlorophenyl)sulfonyl-1,5-dimethyl-N-[(2-methylquinazolin-5-yl)methyl]pyrrole-2- carboxamide;4-(4-chlorophenyl)sulfonyl-1,5-dimethyl-N-(quinazolin-5-ylmethyl)pyrrole-2-carboxamide;4-((1 H-indazol-5-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H-pyrrole-2- carboxamide;4-(1 H-indazol-5-ylsulfonyl)-1 ,5-dimethyl-N-[(2-methylquinazolin-5-yl)methyl]pyrrole-2- carboxamide;4-(1 H-indazol-5-ylsulfonyl)-1 ,5-dimethyl-N-(quinazolin-5-ylmethyl)pyrrole-2-carboxamide;N-((1 ,6-naphthyridin-5-yl)methyl)-4-((1 H-indazol-5-yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2- carboxamide;4-((1 H-indazol-5-yl)sulfonyl)-N-((6-chloro-2-methylquinazolin-5-yl)methyl)-1 ,5-dimethyl-1 H- pyrrole-2-carboxamide;N-((1-aminoisoquinolin-4-yl)methyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H- pyrrole-2-carboxamide;1 ,5-dimethyl-4-((7-methyl-1 H-indazol-5-yl)sulfonyl)-N-(quinazolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;N-((1 ,6-naphthyridin-5-yl)methyl)-1 ,5-dimethyl-4-((7-methyl-1 H-indazol-5-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;N-((1 ,7-naphthyridin-5-yl)methyl)-1 ,5-dimethyl-4-((7-methyl-1 H-indazol-5-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;4-(1 H-indazol-5-ylsulfonyl)-1 ,5-dimethyl-N-[(2-methylquinazolin-5-yl)methyl]pyrrole-2- carboxamide;4-((1,3-dihydroisobenzofuran-5-yl)sulfonyl)-1 ,5-dimethyl-N-((2-methylpyrido[4,3-d]pyrimidin-5-yl)methyl)-1H-pyrrole-2-carboxamide;N-((1 ,6-naphthyridin-5-yl)methyl)-4-((1 ,3-dihydroisobenzofuran-5-yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;4-(1,3-dihydroisobenzofuran-5-ylsulfonyl)-1,5-dimethyl-N-[(2-methylquinazolin-5- yl)methyl]pyrrole-2-carboxamide;4-((1 ,3-dihydroisobenzofuran-5-yl)sulfonyl)-1 ,5-dimethyl-N-(quinazolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;4-((1,3-dihydroisobenzofuran-5-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H- pyrrole-2-carboxamide;4-((1 H-indol-5-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H-pyrrole-2- carboxamide;N-((1 ,6-naphthyridin-5-yl)methyl)-4-((1 ,3-dihydroisobenzofuran-5-yl)sulfonyl)-1 ,5-dimethyl- 1 H-pyrrole-2-carboxamide;4-((1 H-indol-5-yl)sulfonyl)-N-((6-fluoroimidazo[1 ,2-a]pyridin-5-yl)methyl)-1 ,5-dimethyl-1 H- pyrrole-2-carboxamide;4-((1 H-indol-5-yl)sulfonyl)-N-(imidazo[1 ,2-a]pyridin-5-ylmethyl)-1 ,5-dimethyl-1 H-pyrrole-2- carboxamide;4-(1 H-indol-5-ylsulfonyl)-1,5-dimethyl-N-[(2-methylquinazolin-5-yl)methyl]pyrrole-2- carboxamide;4-(1 H-indol-5-ylsulfonyl)-1,5-dimethyl-N-(1,6-naphthyridin-5-ylmethyl)pyrrole-2-carboxamide;N-((6-fluoroimidazo[1,2-a]pyridin-5-yl)methyl)-1 ,5-dimethyl-4-((7-methyl-1 ,4,6,7-tetrahydro- 5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;(S)-1,5-dimethyl-4-((7-methyl-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N- ((2-methylquinazolin-5-yl)methyl)-1 H-pyrrole-2-carboxamide;(R)-1,5-dimethyl-4-((7-methyl-1 ,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N- ((2-methylquinazolin-5-yl)methyl)-1 H-pyrrole-2-carboxamide;(S)-1,5-dimethyl-4-((7-methyl-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N- ((2-methylquinazolin-5-yl)methyl)-1 H-pyrrole-2-carboxamide;(R)-1,5-dimethyl-4-((7-methyl-1 ,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N- ((2-methylquinazolin-5-yl)methyl)-1 H-pyrrole-2-carboxamide;1.5-dimethyl-4-[(7-methyl-1 ,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)sulfonyl]-N-(1 ,6- naphthyridin-5-ylmethyl)pyrrole-2-carboxamide;1.5-dimethyl-N-(quinazolin-5-ylmethyl)-4-((1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridin-5- yl)sulfonyl)-1H-pyrrole-2-carboxamide;1.5-dimethyl-4-(pyrazolo[1,5-a]pyridin-5-ylsulfonyl)-N-(quinazolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-((6-methyl-1 H-indazol-5-yl)sulfonyl)-N-((2-methylquinazolin-5-yl)methyl)-1 H- pyrrole-2-carboxamide;1.5-dimethyl-4-((4-methyl-1 H-indazol-5-yl)sulfonyl)-N-((2-methylquinazolin-5-yl)methyl)-1 H- pyrrole-2-carboxamide;4-((7-chloro-1 H-indazol-5-yl)sulfonyl)-1 ,5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-1 H- pyrrole-2-carboxamide;4-((7-fluoro-1 H-indazol-5-yl)sulfonyl)-1 ,5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-1 H- pyrrole-2-carboxamide;4-((7-methoxy-1H-indazol-5-yl)sulfonyl)-1,5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-1 H- pyrrole-2-carboxamide;N-((4-chloro-2-methoxypyridin-3-yl)methyl)-4-((5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;4-((5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)sulfonyl)-N-((4-fluoro-2-methoxypyridin-3- yl)methyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;4-((5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)sulfonyl)-N-(2-fluoro-6-methoxybenzyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;4-((5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)sulfonyl)-N-((6-fluoroquinazolin-5-yl)methyl)-1.5-dimethyl-1 H-pyrrole-2-carboxamide;4-(6,7-dihydro-4H-pyrazolo[1 ,5-a]pyrazin-5-ylsulfonyl)-N-(imidazo[1,5-a]pyrimidin-6- ylmethyl)-1,5-dimethyl-pyrrole-2-carboxamide;4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-1 ,5-dimethyl-N-(quinazolin-5- ylmethyl)-1H-pyrrole-2-carboxamide;(S)-1,5-dimethyl-4-((7-methyl-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N- (quinazolin-5-ylmethyl)-1H-pyrrole-2-carboxamide;(R)-1,5-dimethyl-4-((7-methyl-1 ,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N- (quinazolin-5-ylmethyl)-1H-pyrrole-2-carboxamide;(S) -1 ,5-dimethyl-4-((7-methyl-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N- (quinazolin-5-ylmethyl)-1H-pyrrole-2-carboxamide;(R)-1,5-dimethyl-4-((7-methyl-1 ,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N- (quinazolin-5-ylmethyl)-1H-pyrrole-2-carboxamide;1.5-dimethyl-4-((5-methyl-5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)sulfonyl)-N-(quinazolin-5-ylmethyl)-1H-pyrrole-2-carboxamide;4-(((3S,4R)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-1H-pyrrole-2-carboxamide;4-(((3S,4R)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinazolin-5- ylmethyl)-1H-pyrrole-2-carboxamide;N-((4-chloro-2-methoxypyridin-3-yl)methyl)-4-(((3S,4R)-4-hydroxy-3-methylpiperidin-1- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((4-fluoro-2-methoxypyridin-3-yl)methyl)-4-(((3R,4R)-4-hydroxy-3-methylpiperidin-1- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;4-(N-(cyclopropylmethyl)-N-methylsulfamoyl)-N-((6-fluoroquinolin-5-yl)methyl)-1,5-dimethyl- 1 H-pyrrole-2-carboxamide;N-[(6-fluoro-5-quinolyl)methyl]-1 ,5-dimethyl-4-(4-oxa-7-azaspiro[2.5]octan-7- ylsulfonyl)pyrrole-2-carboxamide;5-chloro-1-methyl-N-[(2-methylquinazolin-5-yl)methyl]-4-(1 ,4,6,7-tetrahydropyrazolo[4,3- c]pyridin-5-ylsulfonyl)pyrrole-2-carboxamide;4-((1 H-indazol-5-yl) sulfonyl)-5-chloro-N-((6-chloro-2-methylquinazolin-5-yl)methyl)-1-methyl- 1 H-pyrrole-2-carboxamide;N-((1 ,6-naphthyridin-5-yl)methyl)-5-chloro-1-methyl-4-((7-methyl-1 H-indazol-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;4-((1 H-indazol-5-yl)sulfonyl)-5-chloro-1-methyl-N-((2-methylquinazolin-5-yl)methyl)-1 H- pyrrole-2-carboxamide;5-(aminomethyl)-4-((6,7-dihydro-1 H-pyrazolo[4,3-c]pyridin-5(4H)-yl)sulfonyl)-1-methyl-N-((2- methylquinazolin-5-yl)methyl)-1 H-pyrrole-2-carboxamide;5-(hydroxymethyl)-1-methyl-N-[(2-methylquinazolin-5-yl)methyl]-4-(1 , 4,6,7- tetrahydropyrazolo[4,3-c]pyridin-5-ylsulfonyl)pyrrole-2-carboxamide;4-((6,7-dihydro-1 H-pyrazolo[4,3-c]pyridin-5(4H)-yl)sulfonyl)-5-(fluoromethyl)-1-methyl-N-((2- methylquinazolin-5-yl)methyl)-1 H-pyrrole-2-carboxamide;5-(difluoromethyl)-4-((6,7-dihydro-1 H-pyrazolo[4,3-c]pyridin-5(4H)-yl)sulfonyl)-1-methyl-N- ((2-methylquinazolin-5-yl)methyl)-1 H-pyrrole-2-carboxamide;4-([1 ,2, 3]triazolo[1 ,5-a]pyridin-5-ylsulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H- pyrrole-2-carboxamide; and(5-((2-chloro- 5-(((6-chloro-2-methylquinazolin-5-yl)methyl) carbamoyl)- 1 -methyl- 1 H-pyrrol-3- yl)sulfonyl)-1 H-indazol-1-yl)methyl dihydrogen phosphate;or a pharmaceutically acceptable salt or solvate thereof.

[0186] The various functional groups and substituents making up the compounds of the Formula (I) are typically chosen such that the molecular weight of the compound of the Formula (I) does not exceed 1000. More usually, the molecular weight of the compound will be less than 900, for example less than 800, or less than 750, or less than 700, or less than 650. More preferably, the molecular weight is less than 600 and, for example, is 550 or less.

[0187] A suitable pharmaceutically acceptable salt of a compound of the invention is, for example, an acid-addition salt of a compound of the invention which is sufficiently basic, for example, an acid-addition salt with, for example, an inorganic or organic acid, for example hydrochloric, hydrobromic, sulfuric, phosphoric, trifluoroacetic, formic, citric methane sulfonate or maleic acid. In addition, a suitable pharmaceutically acceptable salt of a compound of theinvention which is sufficiently acidic is an alkali metal salt, for example a sodium or potassium salt, an alkaline earth metal salt, for example a calcium or magnesium salt, an ammonium salt or a salt with an organic base which affords a pharmaceutically acceptable cation, for example a salt with methylamine, dimethylamine, trimethylamine, piperidine, morpholine or tris-(2-hydroxyethyl)amine.

[0188] Compounds that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or the arrangement of their atoms in space are termed “isomers”. Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers”. Stereoisomers that are not mirror images of one another are termed “diastereomers” and those that are non-superimposable mirror images of each other are termed “enantiomers”. When a compound has an asymmetric center, for example, it is bonded to four different groups, a pair of enantiomers is possible. An enantiomer can be characterized by the absolute configuration of its asymmetric center and is described by the R- and S-sequencing rules of Cahn and Prelog, or by the manner in which the molecule rotates the plane of polarized light and designated as dextrorotatory or levorotatory (i.e., as (+) or (-)-isomers respectively). A chiral compound can exist as either individual enantiomer or as a mixture thereof. A mixture containing equal proportions of the enantiomers is called a “racemic mixture”.

[0189] The compounds of this invention may possess one or more asymmetric centers; such compounds can therefore be produced as individual (R)- or (S)-stereoisomers or as mixtures thereof. Unless indicated otherwise, the description or naming of a particular compound in the specification and claims is intended to include both individual enantiomers and mixtures, racemic or otherwise, thereof. The methods for the determination of stereochemistry and the separation of stereoisomers are well-known in the art (see discussion in Chapter 4 of “Advanced Organic Chemistry”, 4th edition J. March, John Wiley and Sons, New York, 2001), for example by synthesis from optically active starting materials or by resolution of a racemic form. Some of the compounds of the invention may have geometric isomeric centres (E- and Z- isomers). It is to be understood that the present invention encompasses all optical, diastereoisomers and geometric isomers and mixtures thereof that possess activity herein, , e.g. against NSP14.

[0190] The present invention also encompasses compounds of the invention as defined herein which comprise one or more isotopic substitutions. For example, H may be in any isotopic form, including1H,2H(D), and3H (T); C may be in any isotopic form, including12C,13C, and14C; and O may be in any isotopic form, including16O and18O; and the like.

[0191] It is also to be understood that certain compounds of the Formula (I) (and compounds of subformulas thereof) may exist in solvated as well as unsolvated forms such as, for example, hydrated forms. It is to be understood that the invention encompasses all such solvated forms that possess the activity described herein, e.g. against NSP14.

[0192] It is also to be understood that certain compounds of the Formula (I) (and compounds of subformulas thereof) may exhibit polymorphism, and that the invention encompasses all such forms that possess the activity described herein, e.g. against NSP14.

[0193] Compounds of the Formula (I) (and compounds of subformulas thereof) may exist in a number of different tautomeric forms and references to compounds of the Formula (I) include all such forms. For the avoidance of doubt, where a compound can exist in one of several tautomeric forms, and only one is specifically described or shown, all others are nevertheless embraced by Formula (I). Examples of tautomeric forms include keto-, enol-, and enolate- forms, as in, for example, the following tautomeric pairs: keto / enol (illustrated below), imine / enamine, amide / imino alcohol, amidine / amidine, nitroso / oxime, thioketone / enethiol, and nitro / aci-nitro.keto enol enolate

[0194] Compounds of the Formula (I) containing an amine function may also form N-oxides. A reference herein to a compound of the Formula (I) that contains an amine function also includes the N-oxide. Where a compound contains several amine functions, one or more than one nitrogen atom may be oxidised to form an N-oxide. Particular examples of N-oxides are the N-oxides of a tertiary amine or a nitrogen atom of a nitrogen-containing heterocycle. N- Oxides can be formed by treatment of the corresponding amine with an oxidizing agent such as hydrogen peroxide or a per-acid (e.g. a peroxycarboxylic acid), see for example Advanced Organic Chemistry, by Jerry March, 4thEdition, Wiley Interscience, pages. More particularly, N-oxides can be made by the procedure of L. W. Deady (Syn. Comm. 1977, 7, 509-514) in which the amine compound is reacted with m-chloroperoxybenzoic acid (mCPBA), for example, in an inert solvent such as dichloromethane.

[0195] The compounds of Formula (I) may be administered in the form of a pro-drug which is broken down in the human or animal body to release a compound of the invention. A prodrug may be used to alter the physical properties and / or the pharmacokinetic properties of a compound of the invention. A pro-drug can be formed when the compound of the invention contains a suitable group or substituent to which a property-modifying group can be attached. Examples of pro-drugs include in vivo cleavable ester derivatives that may be formed at acarboxy group or a hydroxy group in a compound of the Formula (I) and in-vivo cleavable amide derivatives that may be formed at a carboxy group or an amino group in a compound of the Formula (I).

[0196] Accordingly, the present invention includes those compounds of the Formula (I) as defined hereinbefore when made available by organic synthesis and when made available within the human or animal body by way of cleavage of a pro-drug thereof. Accordingly, the present invention includes those compounds of the Formula (I) that are produced by organic synthetic means and also such compounds that are produced in the human or animal body by way of metabolism of a precursor compound, that is a compound of the Formula (I) may be a synthetically-produced compound or a metabolically-produced compound.

[0197] A suitable pharmaceutically acceptable pro-drug of a compound of the Formula (I) is one that is based on reasonable medical judgement as being suitable for administration to the human or animal body without undesirable pharmacological activities and without undue toxicity.

[0198] Various forms of pro-drug have been described, for example in the following documents :- a) Methods in Enzymology, Vol. 42, p. 309-396, edited by K. Widder, et al. (Academic Press, 1985); b) Design of Pro-drugs, edited by H. Bundgaard, (Elsevier, 1985); c) A Textbook of Drug Design and Development, edited by Krogsgaard-Larsen and H. Bundgaard, Chapter 5 “Design and Application of Pro-drugs”, by H. Bundgaard p. 113-191 (1991); d) H. Bundgaard, Advanced Drug Delivery Reviews, 8, 1-38 (1992); e) H. Bundgaard, et al., Journal of Pharmaceutical Sciences, 77, 285 (1988); f) N. Kakeya, et al., Chem. Pharm. Bull., 32, 692 (1984); g) T. Higuchi and V. Stella, “Pro-Drugs as Novel Delivery Systems”, A.C.S. Symposium Series, Volume 14; and h) E. Roche (editor), “Bioreversible Carriers in Drug Design”, Pergamon Press, 1987.

[0199] A suitable pharmaceutically acceptable pro-drug of a compound of the Formula (I) that possesses a carboxy group is, for example, an in vivo cleavable ester thereof. An in vivo cleavable ester of a compound of the Formula (I) containing a carboxy group is, for example, a pharmaceutically acceptable ester which is cleaved in the human or animal body to produce the parent acid. Suitable pharmaceutically acceptable esters for carboxy includeCi-ealkyl esters such as methyl, ethyl and terf-butyl, Ci-ealkoxymethyl esters such as methoxymethyl esters, Ci-ealkanoyloxymethyl esters such as pivaloyloxymethyl esters,3-phthalidyl esters, Cs-scycloalkylcarbonyloxy- Ci-ealkyl esters such as cyclopentylcarbonyloxymethyl and 1 -cyclohexylcarbonyloxyethyl esters,2-oxo-1,3-dioxolenylmethyl esters such as 5-methyl-2-oxo-1,3-dioxolen-4-ylmethyl esters and Ci-ealkoxycarbonyloxy- Ci-ealkyl esters such as methoxycarbonyloxymethyl and 1- methoxycarbonyloxyethyl esters.

[0200] A suitable pharmaceutically acceptable pro-drug of a compound of the Formula (I) that possesses a hydroxy group is, for example, an in vivo cleavable ester or ether thereof. An in vivo cleavable ester or ether of a compound of the Formula (I) containing a hydroxy group is, for example, a pharmaceutically acceptable ester or ether which is cleaved in the human or animal body to produce the parent hydroxy compound. Suitable pharmaceutically acceptable ester forming groups for a hydroxy group include inorganic esters such as phosphate esters (including phosphoramidic cyclic esters). Further suitable pharmaceutically acceptable ester forming groups for a hydroxy group include Ci- alkanoyl groups such as acetyl, benzoyl, phenylacetyl and substituted benzoyl and phenylacetyl groups, Ci- alkoxycarbonyl groups such as ethoxycarbonyl, / V, / V-(Ci ^carbamoyl, 2-dialkylaminoacetyl and 2-carboxyacetyl groups. Examples of ring substituents on the phenylacetyl and benzoyl groups include aminomethyl, / V-alkylaminomethyl, / V, / V-dialkylaminomethyl, morpholinomethyl, piperazin-1 -ylmethyl and 4-(Ci-4alkyl)piperazin-1-ylmethyl. Suitable pharmaceutically acceptable ether forming groups for a hydroxy group include a-acyloxyalkyl groups such as acetoxymethyl and pivaloyloxymethyl groups.

[0201] A suitable pharmaceutically acceptable pro-drug of a compound of the Formula (I) that possesses a carboxy group is, for example, an in vivo cleavable amide thereof, for example an amide formed with an amine such as ammonia, a Ci-4alkylamine such as methylamine, a (Ci-4alkyl)2amine such as dimethylamine, / V-ethyl- / V-methylamine or diethylamine, a Ci-4alkoxy- C^alkylamine such as 2-methoxyethylamine, a phenyl-Ci- 4alkylamine such as benzylamine and amino acids such as glycine or an ester thereof.

[0202] A suitable pharmaceutically acceptable pro-drug of a compound of the Formula (I) that possesses an amino group is, for example, an in vivo cleavable amide derivative thereof. Suitable pharmaceutically acceptable amides from an amino group include, for example an amide formed with Ci- alkanoyl groups such as an acetyl, benzoyl, phenylacetyl and substituted benzoyl and phenylacetyl groups. Examples of ring substituents on the phenylacetyl and benzoyl groups include aminomethyl, / V-alkylaminomethyl, N,N- dialkylaminomethyl, morpholinomethyl, piperazin- 1 -ylmethyl and4-(Ci-4alkyl)piperazin-1 -ylmethyl.

[0203] The in vivo effects of a compound of the Formula (I) may be exerted in part by one or more metabolites that are formed within the human or animal body after administration of a compound of the Formula (I). As stated hereinbefore, the in vivo effects of a compound of the Formula (I) may also be exerted by way of metabolism of a precursor compound (a prodrug).

[0204] Though the present invention may relate to any compound or particular group of compounds defined herein by way of optional, preferred or suitable features or otherwise in terms of particular embodiments, the present invention may also relate to any compound or particular group of compounds that specifically excludes said optional, preferred or suitable features or particular embodiments.

[0205] Suitably, the present invention excludes any individual compounds not possessing the biological activity defined herein.Synthesis

[0206] The compounds of the present invention can be prepared by any suitable technique known in the art. Particular processes for the preparation of these compounds are described further in the accompanying examples.

[0207] In the description of the synthetic methods described herein and in any referenced synthetic methods that are used to prepare the starting materials, it is to be understood that all proposed reaction conditions, including choice of solvent, reaction atmosphere, reaction temperature, duration of the experiment and workup procedures, can be selected by a person skilled in the art.

[0208] It is understood by one skilled in the art of organic synthesis that the functionality present on various portions of the molecule must be compatible with the reagents and reaction conditions utilised.

[0209] It will be appreciated that during the synthesis of the compounds of the invention in the processes defined herein, or during the synthesis of certain starting materials, it may be desirable to protect certain substituent groups to prevent their undesired reaction. The skilled chemist will appreciate when such protection is required, and how such protecting groups may be put in place, and later removed.

[0210] For examples of protecting groups see one of the many general texts on the subject, for example, ‘Protective Groups in Organic Synthesis’ by Theodora Green (publisher: John Wiley & Sons). Protecting groups may be removed by any convenient method described in the literature or known to the skilled chemist as appropriate for the removal of the protectinggroup in question, such methods being chosen so as to effect removal of the protecting group with the minimum disturbance of groups elsewhere in the molecule.

[0211] Thus, if reactants include, for example, groups such as amino, carboxy or hydroxy it may be desirable to protect the group in some of the reactions mentioned herein.

[0212] By way of example, a suitable protecting group for an amino or alkylamino group is, for example, an acyl group, for example an alkanoyl group such as acetyl, an alkoxycarbonyl group, for example a methoxycarbonyl, ethoxycarbonyl or t-butoxycarbonyl group, an arylmethoxycarbonyl group, for example benzyloxycarbonyl, or an aroyl group, for example benzoyl. The deprotection conditions for the above protecting groups necessarily vary with the choice of protecting group. Thus, for example, an acyl group such as an alkanoyl or alkoxycarbonyl group or an aroyl group may be removed by, for example, hydrolysis with a suitable base such as an alkali metal hydroxide, for example lithium or sodium hydroxide. Alternatively an acyl group such as a terf-butoxycarbonyl group may be removed, for example, by treatment with a suitable acid as hydrochloric, sulfuric or phosphoric acid or trifluoroacetic acid and an arylmethoxycarbonyl group such as a benzyloxycarbonyl group may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon, or by treatment with a Lewis acid for example boron tris(trifluoroacetate). A suitable alternative protecting group for a primary amino group is, for example, a phthaloyl group which may be removed by treatment with an alkylamine, for example dimethylaminopropylamine, or with hydrazine.

[0213] A suitable protecting group for a hydroxy group is, for example, an acyl group, for example an alkanoyl group such as acetyl, an aroyl group, for example benzoyl, or an arylmethyl group, for example benzyl. The deprotection conditions for the above protecting groups will necessarily vary with the choice of protecting group. Thus, for example, an acyl group such as an alkanoyl or an aroyl group may be removed, for example, by hydrolysis with a suitable base such as an alkali metal hydroxide, for example lithium, sodium hydroxide or ammonia. Alternatively an arylmethyl group such as a benzyl group may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon.

[0214] A suitable protecting group for a carboxy group is, for example, an esterifying group, for example a methyl or an ethyl group which may be removed, for example, by hydrolysis with a base such as sodium hydroxide, or for example a f-butyl group which may be removed, for example, by treatment with an acid, for example an organic acid such as trifluoroacetic acid, or for example a benzyl group which may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon.

[0215] Resins may also be used as a protecting group.

[0216] The methodology employed to synthesise a compound of Formula (I) will vary depending on the nature of the variable groups. Suitable processes for their preparation are described further in the accompanying Examples.

[0217] Once a compound of Formula (I) has been synthesised by any one of the processes defined herein, the processes may then further comprise the additional steps of:(i) removing any protecting groups present;(ii) converting the compound Formula (I) into another compound of Formula (I);(iii) forming a pharmaceutically acceptable salt, hydrate or solvate thereof; and / or(iv) forming a prodrug thereof.

[0218] The resultant compounds of Formula (I) can be isolated and purified using techniques well known in the art.Biological Activity

[0219] The NSP14 enzyme and cell assays described in accompanying Example section may be used to measure the pharmacological effects of the compounds of the present invention.

[0220] Although the pharmacological properties of the compounds of Formula (I) vary with structural change, as expected, the compounds of the invention were found to be active in these NSP14 assays.

[0221] In general, the compounds of the invention demonstrate an IC50 of 1.5 pM or less in the NSP14 SARS-CoV1 enzyme assay described in the examples section, with particularly preferred compounds of the invention demonstrating an IC50 of 500 nM or less and the most preferred compounds of the invention demonstrating an IC50 of 100 nM or less.Pharmaceutical Compositions

[0222] According to a further aspect of the invention there is provided a pharmaceutical composition which comprises a compound of the invention as defined hereinbefore, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

[0223] The compositions of the invention may be in a form suitable for oral use (for example as tablets, lozenges, hard or soft capsules, aqueous or oily suspensions, emulsions, dispersible powders or granules, syrups or elixirs), for topical use (for example as creams, ointments, gels, or aqueous or oily solutions or suspensions), for administration by inhalation (for example as a finely divided powder or a liquid aerosol), for administration by insufflation (for example as a finely divided powder) or for parenteral administration (for example as asterile aqueous or oily solution for intravenous, subcutaneous, intramuscular, intraperitoneal or intramuscular dosing or as a suppository for rectal dosing).

[0224] The compositions of the invention may be obtained by conventional procedures using conventional pharmaceutical excipients, well known in the art. Thus, compositions intended for oral use may contain, for example, one or more colouring, sweetening, flavouring and / or preservative agents.

[0225] An effective amount of a compound of the present invention for use in therapy is an amount sufficient to inhibit viral replication of any of the viruses referred to herein, slow its progression and / or reduce the symptoms associated with the condition and / or disease.

[0226] The amount of active ingredient that is combined with one or more excipients to produce a single dosage form will necessarily vary depending upon the individual treated and the particular route of administration. For example, a formulation intended for oral administration to humans will generally contain, for example, from 0.5 mg to 0.5 g of active agent (more suitably from 0.5 to 100 mg, for example from 1 to 30 mg) compounded with an appropriate and convenient amount of excipients which may vary from about 5 to about 98 percent by weight of the total composition.

[0227] The size of the dose for therapeutic or prophylactic purposes of a compound of the Formula (I) will naturally vary according to the nature and severity of the conditions, the age and sex of the animal or patient and the route of administration, according to well known principles of medicine.

[0228] In using a compound of the invention for therapeutic or prophylactic purposes it will generally be administered so that a daily dose in the range, for example, 0.1 mg / kg to 75 mg / kg body weight is received, given if required in divided doses. In general lower doses will be administered when a parenteral route is employed. Thus, for example, for intravenous or intraperitoneal administration, a dose in the range, for example, 0.1 mg / kg to 30 mg / kg body weight will generally be used. Similarly, for administration by inhalation, a dose in the range, for example, 0.05 mg / kg to 25 mg / kg body weight will be used. Oral administration may also be suitable, particularly in tablet form. Typically, unit dosage forms will contain about 0.5 mg to 0.5 g of a compound of this invention.Therapeutic Uses and Applications

[0229] The present invention provides compounds, or a pharmaceutically acceptable salts, hydrates or solvates thereof, that function as inhbitiors of an enzyme which binds guanosine monophosphate, guanosine diphosphate, guanosine triphosphate or 5’ guanosine triphosphate capped RNA.

[0230] Enzymes which bind GMP, GDP, GTP or 5’ GTP capped RNA can be found in a number of viruses, including human and animal viruses. Such viruses include but are not limited to: SARS-CoV-2 (causing COVID-19), SARS-CoV (causing severe acute respiratory syndrome (SARS)); SARS-Cov-1 related coronavirus (e.g. SHC014-CoV, WIV1); MERS-CoV (causing Middle East respiratory syndrome); HCov-OC43 (causing, inter alia, common cold, pneumonia and bronchiolitis); HCov-229E (causing, inter alia, common cold, pneumonia and bronchiolitis); HCov-HKU (causing, inter alia, common cold, pneumonia and bronchiolitis); HCov-NL63 (causing, inter alia, common cold, pneumonia and bronchiolitis); TGEV (causing transmissible gastroenteritis virus); IBV (causing avian infectious bronchitis virus); Bovine coronavirus; Porcine Deltacoronavirus (PDCoV-HKU15); feline coronavirus (causing Feline infectious peritonitis); Canine coronavirus; Murine Coronavirus (MHV); Porcine Epidemic Diarrhea Virus (PEDV); Pangolin origin Coronaviruses (e.g. pCov-GD01); Noroviruses (e.g. Norwalk virus [NV] causing gastroenteritis); human rhinovirus (HRV); enterovirus 71 (EV71); poliovirus (PV); foot-and-mouth disease virus (FMDV); hepatitis A virus (HAV); hepatitis E virus (HEV); porcine teschovirus (PTV); Pneumoviridae (e.g. Respiratory Syncytial Virus and Human Metapneumovirus); Paramyxoviridae (e.g. Human Parainfluenza Virus, Measles and Henipaviruses including Nipah); Flaviviridae (e.g. Dengue Virus DENV1-4, West Nile fever virus, Yellow ever virus, Zika virus, Japanese encephalitis virus, tick borne encephalitis virus, llsutu virus, Powassan virus); Togaviridae alphavirus (e.g. Chikungunya virus, Venezuelan equine encephalitis virus, Eastern equine encephalitis virus, Mayaro virus, Sindbis virus, O’nyong’nyong virus, Ross River virus, Una virus, Western equine encephalitis virus); Matonaviridae (e.g. Rubella virus); Phenuiviridae (e.g. Rift Valley Fever virus); Arenaviridae mammarenavirus (Lassa virus); Rhabdoviridae (e.g. Rabies); Filoviridae (e.g. Ebola virus, Marburg virus, Bundibugyo virus, Sudan virus, Tai Forest ebola virus); Orthopoxvirus (e.g. Monkey Pox or Small Pox); Paramyxoviridae henipaviruses (e.g. Nipah, Mojiang, Ghanaian bat henipavirus, Hendra, Langya, Kumasi, Newcastle, Mumps and Madagascar); Paramyxoviridae morbillivirus (e.g. measles); or Nairoviridae othonairovirus (e.g. Crimean- congo hemorrhagic fever virus).

[0231] In an embodiment the enzyme which binds guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5’ guanosine triphosphate (GTP) capped RNA is an enzyme comprising a RNA cap Guanine N-7 methyl transferase. RNA cap Guanine N-7 methyl transferases can be found in a number of virus families.

[0232] In a preferred embodiment, the enzyme comprising a RNA cap Guanine N-7 methyl transferase is NSP14, which is found in viruses of the family Coronaviridae, including but not limited to SARS-CoV-2, SARS-CoV, MERS-CoV, HCov-OC43, HCov-229E, HCov- HKU and HCov-NL63, Avian Infectious Bronchitis virus (IBV), Bovine coronavirus, felinecoronavirus, Murine Coronavirus (MHV) and the Porcine Epidemic Diarrhea Virus.

[0233] In a particular embodiment, the present invention provides compounds which exhibit inhibitory activity of enzyme comprising an RNA Guanine cap N-7 methyl transferase. Thus, the compounds of the invention may find use in inhibiting viral replication of a viral RNA Guanine cap N-7 methyl transferase. Thus, the compounds of the invention may find use in the treatment of a disease or disorder in which RNA Guanine cap N-7 methyl transferase activity is implicated.

[0234] Suitably, the enzyme comprising an RNA Guanine cap N-7 methyl transferase may be NSP14. Thus, in a particular embodiment, the present invention provides compounds which exhibit inhibitory activity against NSP14. Thus, the compounds of the invention may find use in the treatment of a disease or disorder in which NSP14 activity is implicated, particularly COVID-19 (caused by SARS-CoV2).

[0235] The NSP14 methyl transferase domain is highly conserved across all variants of SARS-CoV2. Thus, compounds of the present invention would be expected to have activity against all SARS-CoV2 variants. The present invention therefore provides a further therapeutic option to treat new emerging variants of concern, variants of interest and variants under monitoring. For example, the compounds are expected to work against the currently circulating Omicron and it’s subvariants, including but not limited to: EG.5, FL.1.5.1 , XBB.1.16, XBB.1.16.6, HV.1 , XBB.2.3, XBB.1.16.1 , XBB.1.5.70, XBB.1.16.11 , XBB, XBB.1.5, XBB.1.9.1 , GE.1 , EG.6.1 , XBB.1.5.72, XBB.1.42.2, XBB.1.9.2, XBB.1.5.68, XBB.1.5.10, XBB.2.3.8, CH.1.1 , FD.1.1 , XBB.1.5.59, FE.1.1 , EU.1.1 , XBB.1.5.1 , BQ.1, BA.2.12.1 , B.1.1.529, BA.5 and FD.2. This does not discount the compounds being active against emerging strains highlighted by the CDC, the ECDC and WHO and includes strains from legacy variants and subvariants from Delta, Beta and Alpha strains. Thus, in the present invention, a reference to SARS-CoV2 includes all variants and sub-variants thereof.

[0236] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in therapy.

[0237] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in the inhibition of activity of an enzyme which binds guanosine monophosphate, guanosine diphosphate, guanosine triphosphate or 5’ guanosine triphosphate capped RNA.

[0238] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or apharmaceutical composition as defined herein for use in the inhibition of activity of an enzyme comprising an RNA cap Guanine N-7 methyl transferase.

[0239] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in the inhibition of NSP14 activity.

[0240] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in the treatment of a disease or disorder in which the activity of an enzyme which binds guanosine monophosphate, guanosine diphosphate, guanosine triphosphate or 5’ guanosine triphosphate capped RNA is implicated.

[0241] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in the treatment of a disease or disorder in which RNA cap Guanine N-7 methyl transferase activity is implicated.

[0242] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in the treatment of a disease or disorder in which NSP14 enzyme activity is implicated.

[0243] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in the treatment of a viral infection. Suitably, the viral infection is caused by a virus comprising the NSP14 enzyme. Suitably, the virus comprising a the NSP14 enzyme is selected from the family Coronaviridae.

[0244] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in the treatment of a viral infection caused by a virus comprising an enzyme which binds guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5’ guanosine triphosphate (GTP) capped RNA, for example a RNA cap Guanine N-7 methyl transferase, such as NSP14.

[0245] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in the treatment of a viral infection caused by a virus comprising a RNA cap Guanine N-7 methyl transferase.

[0246] According to a further aspect of the present invention, there is provided acompound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in the treatment of a viral infection caused by a virus comprising the enzyme NSP14.

[0247] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in the treatment of a viral infection caused by a virus selected from SARS-CoV-2 (causing COVID- 19), SARS-CoV (causing severe acute respiratory syndrome (SARS)); SARS-Cov-1 related coronavirus (e.g. SHC014- CoV, WIV1); MERS-CoV (causing Middle East respiratory syndrome); HCov-OC43 (causing, inter alia, common cold, pneumonia and bronchiolitis); HCov-229E (causing, inter alia, common cold, pneumonia and bronchiolitis); HCov-HKU (causing, inter alia, common cold, pneumonia and bronchiolitis); HCov-NL63 (causing, inter alia, common cold, pneumonia and bronchiolitis); TGEV (causing transmissible gastroenteritis virus); IBV (causing avian infectious bronchitis virus); Bovine coronavirus; Porcine Deltacoronavirus (PDCoV-HKU15); feline coronavirus (causing Feline infectious peritonitis); Canine coronavirus; Murine Coronavirus (MHV); Porcine Epidemic Diarrhea Virus (PEDV); Pangolin origin Coronaviruses (e.g. pCov-GD01); Noroviruses (e.g. Norwalk virus [NV] causing gastroenteritis); human rhinovirus (HRV); enterovirus 71 (EV71); poliovirus (PV); foot-and-mouth disease virus (FMDV); hepatitis A virus (HAV); hepatitis E virus (HEV); porcine teschovirus (PTV); Pneumoviridae (e.g. Respiratory Syncytial Virus and Human Metapneumovirus); Paramyxoviridae (e.g. Human Parainfluenza Virus, Measles and Henipaviruses including Nipah); Flaviviridae (e.g. Dengue Virus DENV1-4, West Nile fever virus, Yellow ever virus, Zika virus, Japanese encephalitis virus, tick borne encephalitis virus, llsutu virus, Powassan virus); Togaviridae alphavirus (e.g. Chikungunya virus, Venezuelan equine encephalitis virus, Eastern equine encephalitis virus, Mayaro virus, Sindbis virus, O’nyong’nyong virus, Ross River virus, Una virus, Western equine encephalitis virus); Matonaviridae (e.g. Rubella virus); Phenuiviridae (e.g. Rift Valley Fever virus); Arenaviridae mammarenavirus (Lassa virus); Rhabdoviridae (e.g. Rabies); Filoviridae (e.g. Ebola virus, Marburg virus, Bundibugyo virus, Sudan virus, Tai Forest ebola virus); Orthopoxvirus (e.g. Monkey Pox or Small Pox)Paramyxoviridae henipaviruses (e.g. Nipah, Mojiang, Ghanaian bat henipavirus, Hendra, Langya, Kumasi, Mewcastle, Mumps and Madagascar); Paramyxoviridae morbillivirus (e.g. measles); or Nairoviridae othonairovirus (e.g. Crimean-congo hemorrhagic fever virus).

[0248] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in the treatment of a viral infection caused by a virus of the Filoviridae family (e.g. Ebola virus, Marburg virus, Bundibugyo virus,Sudan virus Tai, Forest ebola virus).

[0249] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in the treatment of a viral infection caused by a virus of the Coronaviridae family.

[0250] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in the treatment of a viral infection caused by a virus of the Coronaviridae family (i.e. a coronavirus infection). Suitably, the virus of the Coronaviridae family is selected from SARS-CoV-2, SARS-CoV, MERS-CoV, HCov- OC43, HCov-229E, HCov-HKU and HCov-NL63, Avian Infectious Bronchitis virus (IBV), Bovine coronavirus, feline coronavirus, Murine Coronavirus (MHV) and the Porcine Epidemic Diarrhea Virus. More suitably, the virus of the Coronaviridae family is SARS-CoV-2, SARS- CoV or MERS-CoV. Most suitably, the virus of the Coronaviridae family is SARS-CoV-2.

[0251] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in the treatment of an animal viral infection. Suitably, the animal viral infection is caused by a virus selected from porcine teschovirus (PTV), porcine epidemic diarrhea virus or feline coronavirus (causing Feline infectious peritonitis)

[0252] Thus, the invention provides a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in the treatment of a coronavirus infection. Suitably, the coronavirus infection is COVID-19.

[0253] Thus, the invention provides a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in the treatment of COVID-19

[0254] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in inhibiting viral replication of a virus comprising an enzyme which binds guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5’ guanosine triphosphate (GTP) capped RNA.

[0255] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in inhibiting viral replication of a viruscomprising an RNA Guanine cap N-7 methyl transferase.

[0256] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in inhibiting viral replication of a virus comprising the NSP14 enzyme.

[0257] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in inhibiting SARS-CoV-2 viral replication.

[0258] According to a further aspect of the present invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, for use in the production of a NSP14 inhibitory effect.

[0259] According to a further aspect of the present invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, for use in inhibiting the activity of NSP14 from SARS-CoV-2.

[0260] According to a further aspect of the present invention, there is provided a method of inhibiting activity of an enzyme which binds guanosine monophosphate, guanosine diphosphate, guanosine triphosphate or 5’ guanosine triphosphate capped RNA in vitro or in vivo, said method comprising contacting a cell with an effective amount of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

[0261] According to a further aspect of the present invention, there is provided a method of inhibiting RNA Guanine cap N-7 methyl transferase activity in vitro or in vivo, said method comprising contacting a cell with an effective amount of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

[0262] The present invention therefore provides a method of inhibiting NSP14 activity in vitro or in vivo, said method comprising contacting a cell with an effective amount of a compound, or a pharmaceutically salt, hydrate or solvate thereof.

[0263] According to a further aspect of the present invention, there is provided a method of treating a disease or disorder in which the activity of an enzyme which binds guanosine monophosphate, guanosine diphosphate, guanosine triphosphate or 5’ guanosine triphosphate capped RNA is implicated, in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, ora pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein.

[0264] According to a further aspect of the present invention, there is provided a method of treating a disease or disorder in which RNA cap Guanine N-7 methyl transferase activity is implicated, in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein.

[0265] According to a further aspect of the present invention, there is provided a method of treating a disease or disorder in which NSP14 activity is implicated, in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein.

[0266] According to a further aspect of the present invention, there is provided a method of treating of a viral infection in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein. Suitably, the viral infection is caused by a virus comprising the NSP14 enzyme. Suitably, the virus comprising a the NSP14 enzyme is selected from the family Coronaviridae.

[0267] According to a further aspect of the present invention, there is provided a method of treating a viral infection caused by a virus comprising an enzyme which binds guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5’ guanosine triphosphate (GTP) capped RNA, for example a RNA cap Guanine N- 7 methyl transferase (such as NSP14), in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein.

[0268] According to a further aspect of the present invention, there is provided a method of treating a viral infection caused by a virus comprising a RNA cap Guanine N-7 methyl transferase in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein.

[0269] According to a further aspect of the present invention, there is provided a method of treating a viral infection caused by a virus comprising the enzyme NSP14, in a patient in need of such treatment, said method comprising administering to said patient atherapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein.

[0270] According to a further aspect of the present invention, there is provided a method of treating a viral infection in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, wherein the viral infection is caused by a virus selected from selected from SARS- CoV-2 (causing COVID-19), SARS-CoV (causing severe acute respiratory syndrome (SARS)); SARS-Cov-1 related coronavirus (e.g. SHC014-CoV, WIV1); MERS-CoV (causing Middle East respiratory syndrome); HCov-OC43 (causing, inter alia, common cold, pneumonia and bronchiolitis); HCov-229E (causing, inter alia, common cold, pneumonia and bronchiolitis); HCov-HKU (causing, inter alia, common cold, pneumonia and bronchiolitis); HCov-NL63 (causing, inter alia, common cold, pneumonia and bronchiolitis); TGEV (causing transmissible gastroenteritis virus); IBV (causing avian infectious bronchitis virus); Bovine coronavirus; Porcine Deltacoronavirus (PDCoV-HKU15); feline coronavirus (causing Feline infectious peritonitis); Canine coronavirus; Murine Coronavirus (MHV); Porcine Epidemic Diarrhea Virus (PEDV); Pangolin origin Coronaviruses (e.g. pCov-GD01); Noroviruses (e.g. Norwalk virus [NV] causing gastroenteritis); human rhinovirus (HRV); enterovirus 71 (EV71); poliovirus (PV); foot-and-mouth disease virus (FMDV); hepatitis A virus (HAV); hepatitis E virus (HEV); porcine teschovirus (PTV); Pneumoviridae (e.g. Respiratory Syncytial Virus and Human Metapneumovirus); Paramyxoviridae (e.g. Human Parainfluenza Virus, Measles and Henipaviruses including Nipah); Flaviviridae (e.g. Dengue Virus DENV1-4, West Nile fever virus, Yellow ever virus, Zika virus, Japanese encephalitis virus, tick borne encephalitis virus, llsutu virus, Powassan virus); Togaviridae alphavirus (e.g. Chikungunya virus, Venezuelan equine encephalitis virus, Eastern equine encephalitis virus, Mayaro virus, Sindbis virus, O’nyong’nyong virus, Ross River virus, Una virus, Western equine encephalitis virus); Matonaviridae (e.g. Rubella virus); Phenuiviridae (e.g. Rift Valley Fever virus); Arenaviridae mammarenavirus (Lassa virus); Rhabdoviridae (e.g. Rabies); Filoviridae (e.g. Ebola virus, Marburg virus, Bundibugyo virus, Sudan virus, Tai Forest ebola virus); Orthopoxvirus (e.g. Monkey Pox or Small Pox)Paramyxoviridae henipaviruses (e.g. Nipah, Mojiang, Ghanaian bat henipavirus, Hendra, Langya, Kumasi, Newcastle, Mumps and Madagascar); Paramyxoviridae morbillivirus (e.g. measles); or Nairoviridae othonairovirus (e.g. Crimean- congo hemorrhagic fever virus).

[0271] According to a further aspect of the present invention, there is provided a method of treating a viral infection in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or apharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, wherein the viral infection is caused by a virus of the Filoviridae family (e.g. Ebola virus, Marburg virus, Bundibugyo virus, Sudan virus Tai, Forest ebola virus).

[0272] According to a further aspect of the present invention, there is provided a method of treating a viral infection in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, wherein the viral infection is caused by a virus of the Coronaviridae family.

[0273] According to a further aspect of the present invention, there is provided a method of treating a viral infection in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, wherein the viral infection is caused by a virus of the Coronaviridae family. Suitably, the virus of the Coronaviridae family is selected from SARS-CoV-2, SARS-CoV, MERS-CoV, HCov-OC43, HCov-229E, HCov-HKU and HCov-NL63, Avian Infectious Bronchitis virus (IBV), Bovine coronavirus, feline coronavirus, Murine Coronavirus (MHV) and the Porcine Epidemic Diarrhea Virus. More suitably, the virus of the Coronaviridae family is SARS-CoV-2.

[0274] In another aspect, the present invention provides a method of treating an animal viral infection in an animal of such treatment, said method comprising administering to said animal a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein. Suitably, animal viral infection is caused by a virus selected from porcine teschovirus (PTV), porcine epidemic diarrhea virus or feline coronavirus (causing Feline infectious peritonitis).

[0275] According to a further aspect of the present invention, there is provided a method of treating a coronavirus infection in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein. Suitably, the coronavirus infection is COVID-19.

[0276] According to a further aspect of the present invention, there is provided a method of treating COVID- 19 in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein.

[0277] According to a further aspect of the present invention, there is provided amethod of inhibiting viral replication, in vitro or in vivo, said method comprising contacting a cell with an effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein. Suitably, the virus comprises an enzyme which binds guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5’ guanosine triphosphate (GTP) capped RNA. More suitably, the virus comprises an RNA Guanine cap N-7 methyl transferase, e.g. SARS-CoV-2.

[0278] According to a further aspect of the present invention, there is provided a method of inhibiting SARS-CoV-2 viral replication, in vitro or in vivo, said method comprising contacting a cell with an effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein.

[0279] According to a further aspect of the present invention, there is provided a method of treating a viral infection in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein.

[0280] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament.

[0281] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for the inhibition of activity of an enzyme which binds guanosine monophosphate, guanosine diphosphate, guanosine triphosphate or 5’ guanosine triphosphate capped RNA.

[0282] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in the inhibition of activity of an enzyme comprising an RNA cap Guanine N-7 methyl transferase.

[0283] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for the inhibition of NSP14 activity.

[0284] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for the treatment of a disease or disorder in which the activity of an enzyme which binds guanosine monophosphate, guanosine diphosphate,guanosine triphosphate or 5’ guanosine triphosphate capped RNA is implicated.

[0285] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for the treatment of a disease or disorder in which RNA cap Guanine N-7 methyl transferase activity is implicated.

[0286] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for the treatment of a disease or disorder in which NSP14 enzyme activity is implicated.

[0287] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for the treatment of a viral infection. Suitably, the viral infection is caused by a virus comprising the NSP14 enzyme. Suitably, the virus comprising a the NSP14 enzyme is selected from the family Coronaviridae.

[0288] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for the treatment of a viral infection caused by a virus comprising an enzyme which binds guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5’ guanosine triphosphate (GTP) capped RNA, for example a RNA cap Guanine N-7 methyl transferase, such as NSP14.

[0289] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for the treatment of a viral infection caused by a virus comprising a RNA cap Guanine N-7 methyl transferase.

[0290] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for the treatment of a viral infection caused by a virus comprising the enzyme NSP14.

[0291] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for the treatment of a viral infection caused by a virus selected from SARS-CoV-2 (causing COVID-19), SARS-CoV (causing severe acute respiratory syndrome (SARS)); SARS-Cov-1 related coronavirus (e.g. SHC014-CoV, WIV1); MERS-CoV (causing Middle East respiratory syndrome); HCov-OC43 (causing, inter alia,common cold, pneumonia and bronchiolitis); HCov-229E (causing, inter alia, common cold, pneumonia and bronchiolitis); HCov-HKU (causing, inter alia, common cold, pneumonia and bronchiolitis); HCov-NL63 (causing, inter alia, common cold, pneumonia and bronchiolitis); TGEV (causing transmissible gastroenteritis virus); IBV (causing avian infectious bronchitis virus); Bovine coronavirus; Porcine Deltacoronavirus (PDCoV-HKU15); feline coronavirus (causing Feline infectious peritonitis); Canine coronavirus; Murine Coronavirus (MHV); Porcine Epidemic Diarrhea Virus (PEDV); Pangolin origin Coronaviruses (e.g. pCov-GD01); Noroviruses (e.g. Norwalk virus [NV] causing gastroenteritis); human rhinovirus (HRV); enterovirus 71 (EV71); poliovirus (PV); foot-and-mouth disease virus (FMDV); hepatitis A virus (HAV); hepatitis E virus (HEV); porcine teschovirus (PTV); Pneumoviridae (e.g. Respiratory Syncytial Virus and Human Metapneumovirus); Paramyxoviridae (e.g. Human Parainfluenza Virus, Measles and Henipaviruses including Nipah); Flaviviridae (e.g. Dengue Virus DENV1- 4, West Nile fever virus, Yellow ever virus, Zika virus, Japanese encephalitis virus, tick borne encephalitis virus, llsutu virus, Powassan virus); Togaviridae alphavirus (e.g. Chikungunya virus, Venezuelan equine encephalitis virus, Eastern equine encephalitis virus, Mayaro virus, Sindbis virus, O’nyong’nyong virus, Ross River virus, Una virus, Western equine encephalitis virus); Matonaviridae (e.g. Rubella virus); Phenuiviridae (e.g. Rift Valley Fever virus); Arenaviridae mammarenavirus (Lassa virus); Rhabdoviridae (e.g. Rabies); Filoviridae (e.g. Ebola virus, Marburg virus, Bundibugyo virus, Sudan virus Tai, Forest ebola virus); Orthopoxvirus (e.g. Monkey Pox or Small Pox); Paramyxoviridae henipaviruses (e.g. Nipah, Mojiang, Ghanaian bat henipavirus, Hendra, Langya, Kumasi, Newcastle, Mumps and Madagascar); Paramyxoviridae morbillivirus (e.g. measles); or Nairoviridae othonairovirus (e.g. Crimean-congo hemorrhagic fever virus).

[0292] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for the treatment of a viral infection caused by a virus of the Filoviridae family (e.g. Ebola virus, Marburg virus, Bundibugyo virus, Sudan virus Tai, Forest ebola virus).

[0293] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for the treatment of a viral infection caused by a virus of the Coronaviridae family.

[0294] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for the treatment of a viral infection caused by a virus of the Coronaviridae family (i.e. a coronavirus infection). Suitably, the virus of theCoronaviridae family is selected from SARS-CoV-2, SARS-CoV, MERS-CoV, HCov-OC43, HCov-229E, HCov-HKU and HCov-NL63, Avian Infectious Bronchitis virus (IBV), Bovine coronavirus, feline coronavirus, Murine Coronavirus (MHV) and the Porcine Epidemic Diarrhea Virus. More suitably, the virus of the Coronaviridae family is SARS-CoV-2.

[0295] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for the treatment of an animal viral infection. Suitably, the animal viral infection is caused by a virus selected from porcine teschovirus (PTV), porcine epidemic diarrhea virus or feline coronavirus (causing Feline infectious peritonitis)

[0296] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for the treatment of a coronavirus infection. Suitably, the coronavirus infection is COVID- 19.

[0297] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for the treatment of COVID-19

[0298] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for inhibiting viral replication of a virus comprising an enzyme which binds guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5’ guanosine triphosphate (GTP) capped RNA.

[0299] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for inhibiting viral replication of a virus comprising an RNA Guanine cap N-7 methyl transferase.

[0300] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for inhibiting viral replication of a virus comprising the NSP14 enzyme.

[0301] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for inhibiting SARS-CoV-2 viral replication.

[0302] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as definedherein in the manufacture of a medicament for the production of a NSP14 inhibitory effect.

[0303] According to a further aspect of the present invention, there is provided a use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for inhibiting the activity of NSP14 from SARS- CoV-2.

[0304] Examples of viruses comprising an RNA Guanine cap N-7 methyl transferase, particularly NSP14, include viruses of the Coronaviridae family, including but not limited to SARS-CoV-2, SARS-CoV, MERS-CoV, HCov-OC43, HCov-229E, HCov-HKU and HCov- NL63, Avian Infectious Bronchitis virus (IBV), Bovine coronavirus, feline coronavirus, Murine Coronavirus (MHV) and the Porcine Epidemic Diarrhea Virus. The compounds of the present invention may find utility in the treatment of the diseases caused by these viruses.

[0305] The compounds of the present invention may find utility in the treatment of the diseases caused a virus selected from SARS-CoV-2 (causing COVID-19), SARS-CoV (causing severe acute respiratory syndrome (SARS)); SARS-Cov-1 related coronavirus (e.g. SHC014-CoV, WIV1); MERS-CoV (causing Middle East respiratory syndrome); HCov-OC43 (causing, inter alia, common cold, pneumonia and bronchiolitis); HCov-229E (causing, inter alia, common cold, pneumonia and bronchiolitis); HCov-HKU (causing, inter alia, common cold, pneumonia and bronchiolitis); HCov-NL63 (causing, inter alia, common cold, pneumonia and bronchiolitis); TGEV (causing transmissible gastroenteritis virus); IBV (causing avian infectious bronchitis virus); Bovine coronavirus; Porcine Deltacoronavirus (PDCoV-HKU15); feline coronavirus (causing Feline infectious peritonitis); Canine coronavirus; Murine Coronavirus (MHV); Porcine Epidemic Diarrhea Virus (PEDV); Pangolin origin Coronaviruses (e.g. pCov-GD01); Noroviruses (e.g. Norwalk virus [NV] causing gastroenteritis); human rhinovirus (HRV); enterovirus 71 (EV71); poliovirus (PV); foot-and-mouth disease virus (FMDV); hepatitis A virus (HAV); hepatitis E virus (HEV); porcine teschovirus (PTV); Pneumoviridae (e.g. Respiratory Syncytial Virus and Human Metapneumovirus); Paramyxoviridae (e.g. Human Parainfluenza Virus, Measles and Henipaviruses including Nipah); Flaviviridae (e.g. Dengue Virus DENV1-4, West Nile fever virus, Yellow ever virus, Zika virus, Japanese encephalitis virus, tick borne encephalitis virus, Usutu virus, Powassan virus); Togaviridae alphavirus (e.g. Chikungunya virus, Venezuelan equine encephalitis virus, Eastern equine encephalitis virus, Mayaro virus, Sindbis virus, O’nyong’nyong virus, Ross River virus, Una virus, Western equine encephalitis virus); Matonaviridae (e.g. Rubella virus); Phenuiviridae (e.g. Rift Valley Fever virus); Arenaviridae mammarenavirus (Lassa virus); Rhabdoviridae (e.g. Rabies); Filoviridae (e.g. Ebola virus, Marburg virus, Bundibugyo virus, Sudan virus, Tai Forest ebola virus); Orthopoxvirus (e.g. Monkey Pox or Small Pox); Paramyxoviridae henipaviruses (e.g. Nipah, Mojiang, Ghanaian bat henipavirus, Hendra,Langya, Kumasi, Newcastle, Mumps and Madagascar); Paramyxoviridae morbillivirus (e.g. measles); or Nairoviridae othonairovirus (e.g. Crimean-congo hemorrhagic fever virus).

[0306] In a particular embodiment, the viral infection to be treated is a coronavirus. Preferably the coronavirus is selected from COVID- 19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). More preferably, the coronavirus is COVID- 19.

[0307] The present invention provides a use of a compound, or a pharmaceutically acceptable salt thereof, as defined herein in the manufacture of a medicament for the treatment of a coronavirus infection.

[0308] Suitably, in any of the therapeutic uses and methods described herein, the compound may be selected from:1 ,5-dimethyl-N-(2-methylbenzyl)-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;N-(2-methoxybenzyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide; orN-(2-chlorobenzyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide; or a pharmaceutical salt, solvate or hydrate thereof.Routes of Administration

[0309] The compounds of the invention or pharmaceutical compositions comprising these compounds may be administered to a subject by any convenient route of administration, whether systemically / peripherally or topically (i.e., at the site of desired action).

[0310] Routes of administration include, but are not limited to, oral (e.g, by ingestion); buccal; sublingual; transdermal (including, e.g., by a patch, plaster, etc.); transmucosal (including, e.g., by a patch, plaster, etc.); intranasal (e.g., by nasal spray); ocular (e.g., by eye drops); pulmonary (e.g., by inhalation or insufflation therapy using, e.g., via an aerosol, e.g., through the mouth or nose); rectal (e.g., by suppository or enema); vaginal (e.g., by pessary); parenteral, for example, by injection, including subcutaneous, intradermal, intramuscular, intravenous, intra-arterial, intracardiac, intrathecal, intraspinal, intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subcuticular, intraarticular, subarachnoid, and intrasternal; by implant of a depot or reservoir, for example, subcutaneously or intramuscularly.Combination Therapies

[0311] The antiviral treatment defined hereinbefore may be applied as a sole therapyor may involve, in addition to the compound of the invention, other drugs used for the treatment of the viral infection in question. Suitably, the viral infection may an infection caused by a coronavirus such as SARS-CoV-2.

[0312] In another aspect, the present invention provides a combination comprising a compound of the invention as defined hereinbefore, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and an additional therapeutic agent.

[0313] In another aspect, the present invention provides a combination comprising a compound of the invention as defined hereinbefore, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and ritonavir.

[0314] In another aspect, the present invention provides a compound, as defined herein, in combination with a protease inhibitor, for use in the treatment of a viral infection, e.g. any of the viral infections discussed herein.

[0315] In another aspect, the present invention provides a compound, as defined herein, in combination with ritonavir, for use in the treatment of COVID- 19.

[0316] In an embodiment, the viral infection to be treated is COVID-19. The compound of the invention may be used in combination with a further drug to elicit greater clinical benefit to the patient, such as a larger reduction in COVID-19 symptoms, a faster time to alleviation of symptoms, reduced lung pathology, a larger reduction in the amount of SARS-CoV-2 coronavirus in the patient (viral load), and decreased mortality.

[0317] Additional therapeutic agents that may be used in combination with the compounds of the invention in the treatment of COVID-19 invention include: i. CYP inhibitors such as Ritonavir ii. 3CL protease inhibitors such as Nirmatrelvir, Simnotrelvir, Ensitrelvir, Ibuzatrelvir, CMX990, Simnotrelvir, EDP-235, Pomotrelvir, Olgotrelvir and / or ALG097558; iii. protease inhibitors such as Paxlovid and / or Xiannuoxin; iv. PL protease inhibitors such as Plpro-001 ; v. antivirals such as remdesivir, deuremidevir, galidesivir, favilavir, avifavir, molnupiravir (MK-4482 / EIDD 2801), derivatives of N(4)-hydroxycytidine, AT-527, AT-301 , BLD- 2660, favipiravir, camostat, SLV213, emtrictabine, tenofivir, clevudine, dalcetrapib, boceprevir and / or ABX464; vi. glucocorticoids such as dexamethasone and hydrocortisone; vii. convalescent plasma; viii. a recombinant human plasma such as gelsolin (Rhu-p65N);ix. monoclonal antibodies such as regdanvimab (Regkirova), ravulizumab (Ultomiris), VIR-7831A, R-7832, BRIM 96, BRII-198, COVI- AMG, COVI DROPS (STI-2020), bamlanivimab (LY-CoV555), mavrilimab, leronlimab (PRO140), AZD7442, lenzilumab, infliximab, adalimumab, JS 016, STI-1499 (COVIGUARD), lanadelumab (Takhzyro), canakinumab (Haris), gimsilumab and / or otilimab; x. antibody cocktails such as casirivimab / imdevimab (REGN-Cov2); xi. recombinant fusion protein such as MK-7110 (CD24Fc / SACCOVID); xii. anticoagulants such as heparin and apixaban; xiii. IL-6 receptor agonists such as tocilizumab (Actemra) or sarilumab (Kevzara); xiv. PlKfyve inhibitors such as apilimod dimesylate; xv. RIPK1 inhibitors such as DNL758, DC402234; xvi. VIP receptor agonists such as PB1046; xvii. SGLT2 inhibitors such as dapaglifozin; xviii. TYK inhibitors such as abivertinib; xix. kinase inhibitors such as bemcentinib, acalabrutinib, losmapimod, baricitinib and / or tofacitinib; xx. MEK inhibitors such as ATR-002, PD-0184264, CI-1040, GSK-1120212, GDC-0973, Binimetinib, Selumetinib, PLX-4032, AZD6244, AZD8330, AS-703026, RDEA-119, RO-5126766, RO4987655, PD-0325901, TAK-733, AS703026, PD98059 andPD184352; xxi. H2 blockers such as famotidine; xxii. anthelmintics such as niclosamide, xxiii. furin inhibitors such as diminazene; xxiv. Quercetin and / or Dasatinib; xxv. complement C5a inhibitors; xxvi. modulators of NSP10 / NSP14, NSP9, NSP10, NSP13 and / or NSP15; xxvii. mPro inhibitors such as Nirmatrelvir, Simnotrelvir and Ensetrelvir; xxviii. modulators of METTL3-METTL14 xxix. modulators of ALKBH5, xxx. modulators of FTO, xxxi. modulators of YTHDF1 , xxxii. modulators of YTHDF2, xxxiii. modulators of Fibrillarin, xxxiv. modulators of NSun2; and / or xxxv. modulators of ADAR1.

[0318] Additional therapeutic agents that may be used in combination with thecompounds of the invention in the treatment of COVID-19 invention include: i) modulators of the immune response, for example glucocorticoids such as Dexamethasone, ii) cytokine antagonists such as Tocilizumab or Anakinra, iii) Janus kinase inhibitors such as Baricitinib and Tofacitinib, iv) experimental senolytics such as Navitoclax, v) combined Quercetin / Dasatinib; vi) Complement C5a inhibition; vii) modulators of NSP10 / NSP14, NSP9, NSP10, NSP13 and NSP15; viii) mPro inhibitors such as Nirmatrelvir, Simnotrelvir and Ensetrelvir; ix) anticoagulants such as heparin; x) antibodies vulnerable to resistance mechanisms which block the virus Spike protein, such as Bebtelovimab, Regdanvimab, Sotrovimab, Amubarvimab / Romlusevimab, Bamlanivimab / Etesevimab,Casirivimab / lmdevimab and Cilgavimab / Tixagevimab; xi) inhibitors of Coronavirus polymerases NSP12 such as Remdesivir, Deuremidevir and Molnupirivir; xii) antiviral inhibitors of IMPDH such as Ribavarin and Mycophenolic Acid (MPA); xiii) modulators of METTL3-METTL14; xiv) modulators of ALKBH5; xv) modulators of FTO; xvi) modulators of YTHDF1 and / or YTHDF2; xvii) modulators of Fibrillarin; xviii) modulators of NSun2 xix) modulators of ADAR1 (Adenosine Deaminase Acting on RNA 1).

[0319] Additional therapeutic agents that may be used in combination with the compounds of the invention in the treatment of COVID-19 invention include the following: i. PLpro inhibitors, Apilomod, EIDD-2801 , Ribavirin, Valganciclovir, p-Thymidine, Aspartame, Oxprenolol, Doxycycline, Acetophenazine, lopromide, Riboflavin, Reproterol, 2,2'-Cyclocytidine, Chloramphenicol, Chlorphenesin carbamate,Levodropropizine, Cefamandole, Floxuridine, Tigecycline, Pemetrexed, L(+)- Ascorbic acid, Glutathione, Hesperetin, Ademetionine, Masoprocol, Isotretinoin, Dantrolene, Sulfasalazine Anti-bacterial, Silybin, Nicardipine, Sildenafil, Platycodin, Chrysin, Neohesperidin, Baicalin, Sugetriol-3, 9-diacetate, (-)-Epigallocatechin gallate, Phaitanthrin D, 2-(3,4-Dihydroxyphenyl)-2-[[2-(3,4-dihydroxyphenyl)-3,4- dihydro-5,7-dihydroxy-2H-1-benzopyran-3-yl]oxy]-3,4-dihydro-2H-1-benzopyran- 3,4,5,7-tetrol, 2,2-di(3-indolyl)-3-indolone, (S)-(1S,2R,4aS,5R,8aS)-1-Formamido- 1 ,4a-dimethyl-6-methylene-5-((E)-2-(2-oxo-2,5-dihydrofuran-3- yl)ethenyl)decahydronaphthalen-2-yl-2-amino-3-phenylpropanoate, Piceatannol, Rosmarinic acid, and Magnolol. ii. 3CLpro inhibitors, Lymecycline, Chlorhexidine, Alfuzosin, Cilastatin, Famotidine,Almitrine, Progabide, Nepafenac, Carvedilol, Amprenavir, Tigecycline, Montelukast, Carminic acid, Mimosine, Flavin, Lutein, Cefpiramide, Phenethicillin, Candoxatril, Nicardipine, Estradiol valerate, Pioglitazone, Conivaptan, Telmisartan, Doxycycline, Oxytetracycline, (1S,2R,4aS,5R,8aS)-1-Formamido-1 ,4a-dimethyl-6-methylene-5- ((E)-2-(2-oxo-2,5-dihydrofuran-3-yl)ethenyl)decahydronaphthalen-2-yl5-((R)-1 ,2- dithiolan-3-yl) pentanoate, Betulonal, Chrysin-7-0-p-glucuronide, Andrographiside, (1S,2R,4aS,5R,8aS)-1-Formamido-1 ,4a-dimethyl-6-methylene-5-((E)-2-(2-oxo- 2,5-dihydrofuran-3-yl)ethenyl)decahydronaphthalen-2-yl 2-nitrobenzoate, 2p- Hydroxy-3,4-seco-friedelolactone-27-oic acid (S)-(1 S,2R,4aS,5R,8aS)-1-Formamido-1 ,4a-dimethyl- 6-methylene-5-((E)-2-(2-oxo-2,5-dihydrofuran-3- yl)ethenyl) decahydronaphthalen-2-yl-2-amino-3-phenylpropanoate, Isodecortinol, Cerevisterol, Hesperidin, Neohesperidin, Andrograpanin, 2-((1 R,5R,6R,8aS)-6- Hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2- methylenedecahydronaphthalen-1- yl)ethyl benzoate, Cosmosiin, Cleistocaltone A, 2,2-Di(3-indolyl)-3-indolone, Biorobin, Gnidicin, Phyllaemblinol, Theaflavin 3,3'-di-0- gallate, Rosmarinic acid, Kouitchenside I, Oleanolic acid, Stigmast-5-en-3-ol, Deacetylcentapicrin, and Berchemol. iii. RdRp inhibitors, Valganciclovir, Chlorhexidine, Ceftibuten, Fenoterol, Fludarabine, Itraconazole, Cefuroxime, Atovaquone, Chenodeoxycholic acid, Cromolyn, Pancuronium bromide, Cortisone, Tibolone, Novobiocin, Silybin, Idarubicin Bromocriptine, Diphenoxylate, Benzylpenicilloyl G, Dabigatran etexilate, Betulonal, Gnidicin, 2p,30p-Dihydroxy-3,4-seco-friedelolactone-27-lactone, 14- Deoxy- 11 ,12- didehydroandrographolide, Gniditrin, Theaflavin 3,3'-di-O-gallate, (R)- ((1 R,5aS,6R,9aS)-1 ,5a-Dimethyl-7-methylene-3-oxo-6-((E)-2-(2-oxo-2,5- dihydrofuran-3-yl)ethenyl)decahydro-1 H-benzo[c]azepin-1-yl)methyl2-amino-3-phenylpropanoate, 2p-Hydroxy-3,4-seco-friedelolactone-27-oic acid, 2-(3,4- Dihydroxyphenyl)-2-[[2~(3,4-dihydroxyphenyl)-3,4-dihydro-5,7-dihydroxy-2H-1- benzopyran-3-yl]oxy]-3,4-dihydro-2H-1-benzopyran-3,4,5,7-tetrol, Phyllaemblicin B, 14-hydroxycyperotundone, Andrographiside, 2-((1 R,5R,6R,8aS)-6-Hydroxy-5- (hydroxymethyl)-5,8a-dimethyl-2-methylenedecahydronaphthalen-1-yl)ethyl benzoate, Andrographolide, Sugetriol-3,9- diacetate, Baicalin, (1 S,2R,4aS,5R,8aS)-1-Formamido-1 ,4a-dimethyl-6-methylene-5-((E)-2-(2-oxo-2,5- dihydrofuran-3-yl)ethenyl)decahydronaphthalen-2-yl 5-((R)-1 ,2-dithiolan-3- yl)pentanoate, 1 ,7-Dihydroxy-3-methoxyxanthone, 1 ,2,6- Trimethoxy-8-[(6-0-p-D- xylopyranosyl-p-D-glucopyranosyl)oxy]-9H-xanthen-9-one, and 1 ,8-Dihydroxy-6- methoxy-2-[(6-0-p-D-xylopyranosyl-p-D-glucopyranosyl)oxy]-9H-xanthen-9-one, 8- (P-D-Glucopyranosyloxy)-1 ,3,5-trihydroxy-9H-xanthen-9-one, iv. Additional therapeutic agents such as Diosmin, Hesperidin, MK-3207, Venetoclax, Dihydroergocristine, Bolazine, R428, Ditercalinium, Etoposide, Teniposide, UK- 432097, Irinotecan, Lumacaftor, Velpatasvir, Eluxadoline, Ledipasvir, Lopinavir I Ritonavir + Ribavirin, Alferon, and prednisone. Other additional agents useful in the methods of the present invention include dexamethasone, azithromycin and remdesivir as well as boceprevir, umifenovir and favipiravir. v. Other additional agents such as a-ketoamides compounds designated as 11 r, 13a and 13b, shown below, as described in Zhang, L; Lin, D.; Sun, X.; Rox, K.; Hilgenfeld, R.; X-ray Structure of Main Protease of the Novel Coronavirus SARS- CoV-2 Enables Design of a-Ketoamide Inhibitors; bioRxiv preprint doi: https: / / doi.org / 10.1101 / 2020.02.17.952879Hr 13a 13b vi. Additional agents that can be used in the methods of the present invention include RIG 1 pathway activators such as those described in US Patent No. 9,884,876. vii. Other additional therapeutic agents such as protease inhibitors such as those described in Dai W, Zhang B, Jiang X-M, et ai. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science,2020;368(8497):1331-1335 including compounds such as the compound shown below and a compound designated as DC402234.

[0320] In an embodiment, the additional agent is selected from protease inhibitors such as ritonavir, antivirals such as remdesivir, deuremidevir, galidesivir, favilavir / avifavir, molnupiravir (MK-4482 / EIDD 2801), AT-527, AT-301 , BLD-2660, favipiravir, camostat, SLV213 emtrictabine / tenofivir, clevudine, dalcetrapib, boceprevir and ABX464, glucocorticoids such as dexamethasone and hydrocortisone, convalescent plasma, a recombinant human plasma such as gelsolin (Rhu-p65N), monoclonal antibodies such as regdanvimab (Regkirova), ravulizumab (Ultomiris), VIR-7831A / IR-7832, BRII-196 / BRII-198, COVI- AMG / COVI DROPS (STI-2020), bamlanivimab (LY-CoV555), mavrilimab, leronlimab (PRO140), AZD7442, lenzilumab, infliximab, adalimumab, JS 016, STI-1499 (COVIGUARD), lanadelumab (Takhzyro), canakinumab (Haris), gimsilumab and otilimab, antibody cocktails such as casirivimab / imdevimab (REGN-Cov2), recombinant fusion protein such as MK-7110 (CD24Fc / SACCOVID), anticoagulants such as heparin and apixaban, IL-6 receptor agonists such as tocilizumab (Actemra) and sarilumab (Kevzara), PlKfyve inhibitors such as apilimod dimesylate, RIPK1 inhibitors such as DNL758, DC402234, VIP receptor agonists such as PB1046, SGLT2 inhibitors such as dapaglifozin, TYK inhibitors such as abivertinib, kinase inhibitors such as ATR-002, PD-0184264, CI-1040, GSK-1120212, GDC-0973, Binimetinib, Selumetinib, PLX-4032, AZD6244, AZD8330, AS-703026, RDEA-119, RO-5126766, RO4987655, PD-0325901 , TAK-733, AS703026, PD98059, PD184352, bemcentinib, acalabrutinib, losmapimod, baricitinib and tofacitinib, H2 blockers such as famotidine, anthelmintics such as niclosamide, furin inhibitors such as diminazene.

[0321] The present invention also provides a pharmaceutical composition, comprising the combination as defined hereinbefore, and one or more pharmaceutically acceptable excipients.

[0322] In a preferred embodiment, the compound of the invention is administered in combination with ritonavir. Suitably, the compound of the invention and ritonavir areadministered to the patient orally.

[0323] In an embodiment, about 10 mg to about 1000 mg per day (e.g. 50 to 400 mg) of ritonavir is administered. Suitably, ritonavir is co-administered orally to the patient twice a day.

[0324] Suitably, the compound of the invention, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and about 100 mg (e.g. 75 to 125 mg) of ritonavir are coadministered to the patient twice a day.

[0325] Suitably, a compound of the invention, or a pharmaceutically acceptable salt, hydrate or solvate thereof, is administered orally twice a day.

[0326] Such conjoint treatment may be achieved by way of the simultaneous, sequential or separate dosing of the individual components of the treatment. Such combination products employ the compounds of this invention within the dosage range described hereinbefore and the other pharmaceutically-active agent within its approved dosage range.

[0327] According to this aspect of the invention there is provided a combination for use in the treatment of a viral infection (for example COVID-19) comprising a compound of the invention as defined hereinbefore, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and another anti-viral agent, e.g. ritonavir.

[0328] According to this aspect of the invention there is provided a combination for use in the treatment of a viral infection caused by a virus comprising 3C-like protease, such as a coronavirus infection (for example COVID- 19), comprising a compound of the invention as defined hereinbefore, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and any one of the anti-viral agents listed herein above, e.g. ritonavir.

[0329] In a further aspect of the invention there is provided a compound of the invention or a pharmaceutically acceptable salt, hydrate or solvate thereof, for use in the treatment of COVID-19, in combination with ritonavir.

[0330] Herein, where the term “combination” is used it is to be understood that this refers to simultaneous, separate or sequential administration. In one aspect of the invention “combination” refers to simultaneous administration. In another aspect of the invention “combination” refers to separate administration. In a further aspect of the invention “combination” refers to sequential administration. Where the administration is sequential or separate, the delay in administering the second component should not be such as to lose the beneficial effect of the combination.

[0331] According to a further aspect of the invention there is provided a pharmaceutical composition which comprises a compound of the invention, or apharmaceutically acceptable salt thereof, in combination with an anti-tumour agent (optionally selected from one listed herein above), in association with a pharmaceutically acceptable diluent or carrier.NUMBERED PARAGRAPHSThe following numbered paragraphs define particular aspects and embodiments of the invention.1 . A compound according to Formula (I) below, or a pharmaceutically acceptable salt or solvate thereof:wherein:LA is a linker group of the formula -[CRL1RL2]m- in which m is an integer selected from 1 , 2 or 3, and RL1and RL2are each independently selected from hydrogen or (1 -3C)alkyl;Ri is selected from aryl or heteroaryl, each of which being optionally substituted by one or more RIA substituents, wherein each RIA is independently selected from halo, cyano or a group of the formula:-WA-WB-WC whereinWA is absent or (1-6C)alkylene;WB is absent or selected from -O-, -S-, -N(R1 B)-, -C(O)-, -C(O)O-, -OC(O)-, - C(O)N(R1 B)-, -N(R1 B)C(O)-, -S(O)-, -S(O)2-, -S(O)(=NR1 B)-, -S(O)2N(R1 B)- or N(R1 B)SO2; wherein R1 Bis selected from hydrogen or (1 -3C)alkyl;\Nc is selected from hydrogen, (1 -6C)alkyl), (3-6C)cycloalkyl or heterocyclyl; wherein Wc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1-4C)alkyl, NR1cR1 D, OR1c, C(O)R1c, C(O)OR1c, OC(O)R1c, C(O)N(R1 D)R1c, N(R1 D)C(O)R1c, S(O)qR1c(where q is 0, 1 or 2), S(O)(=NR1 D)R1c, S(O)2N(R1 D)R1cor N(R1 D)S(O)2R1c; wherein R1cand R1 Dare each independently selected from hydrogen, (1- 3C)alkyl or (3-6C)cycloalkyl, wherein (1 -3C)alkyl or (3-6C)cycloalkyl are each optionally substituted with one or more substituents selected from halo, cyano, hydroxy or NH2;Ring A is selected from:Rsxwherein:Xi is selected from O, S, N or NRXIN;X2 is selected from CRx2, O, S, N or NRX2N; wherein:RX2 is selected from hydrogen, hydroxy, halo, cyano, (1-3C)alkyl, (3- 6C)cycloalkyl, OR2A or NR2AR2B, wherein each of R2A and R2B are independently selected from hydrogen or (1 -3C)alkyl; wherein any (1 -3C)alkyl or (3-6C)cycloalkyl is optionally substituted by one or more substituents selected from halo, cyano, (1-3C)alkoxy or hydroxy; andRxiN and Rx2N are independently selected from hydrogen, (1-3C)alkyl or (3-6C)cycloalkyl, each of which being optionally substituted by one or more halo, oxo, methoxy or hydroxy substituents;Rsx is selected from halo, cyano, or a group of the formula-XA-XB-XC whereinXA is absent or (1-6C)alkylene;XB is absent or selected from -O-, -S-, -N(R3A)-, -C(O)-, -C(O)O-, -OC(O)-, - N(R3A)C(O)-, -S(O)-, -S(O)2-, -S(O)(=NR3A)-, -S(O)2N(R3A)- or N(R3A)SO2; wherein R3A is selected from hydrogen or (1 -3C)alkyl;Xc is selected from hydrogen, (1 -6C)alkyl), (3-6C)cycloalkyl or heterocyclyl; ii) wherein Xc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1-4C)alkyl, NR3BR3C, OR3B, C(O)R3B, C(O)OR3B, OC(O)R3B, C(O)N(R3C)R3B, N(R3C)C(O)R3B, S(O)qR3B(where q is 0, 1 or 2), S(O)(=NR3C)R3B, S(O)2N(R3C)R3B or N(R3C)S(O)2R3B; wherein R3B and R3c are each independently selected from hydrogen, (1- 3C)alkyl or (3-6C)cycloalkyl, wherein (1 -3C)alkyl or (3-6C)cycloalkyl are each optionally substituted with one or more substituents selected from halo, cyano, hydroxywherein:Yi is selected from CRY1or N;Y2is selected from CRY2or N;Y3is selected from CRY3or N; wherein each of RY1, RY2and RY3are independently selected from hydrogen, hydroxy, halo, cyano, (1 -3C)alkyl, (3-6C)cycloalkyl, OR2a, NR2aR2b, wherein each of R2aand R2bare independently selected from hydrogen or (1 -3C)alkyl; wherein any (1 -3C)alkyl or (3-6C)cycloalkyl is optionally substituted by one or more substituents selected from halo, cyano, oxo, (1-3C)alkoxy or hydroxy; andR3yis selected from hydrogen, halo, cyano, or a group of the formula-XA-XB-XC whereinXA is absent or (1-6C)alkylene;XB is absent or selected from -O-, -S-, -N(R3A)-, -C(O)-, -C(O)O-, -OC(O)-, - N(R3A)C(O)-, -S(O)-, -S(O)2-, -S(O)(=NR3A)-, -S(O)2N(R3A)- or N(R3A)SO2; wherein R3A is selected from hydrogen or (1 -3C)alkyl;Xc is selected from hydrogen, (1 -6C)alkyl), (3-6C)cycloalkyl or heterocyclyl; wherein Xc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1-4C)alkyl, NR3BR3C, OR3B, C(O)R3B, C(O)OR3B, OC(O)R3B, C(O)N(R3C)R3B, N(R3C)C(O)R3B, S(O)qR3B(where q is 0, 1 or 2), S(O)(=NR3C)R3B, S(O)2N(R3C)R3B or N(R3C)S(O)2R3B; wherein R3B and R3c are each independently selected from hydrogen, (1- 3C)alkyl or (3-6C)cycloalkyl, wherein (1 -3C)alkyl or (3-6C)cycloalkyl are each optionally substituted with one or more substituents selected from halo, cyano, hydroxy or NH2;Z is selected from (1 -4C)alkyl, (3-12C)cycloalkyl, heterocyclyl, aryl, heteroaryl, (3- 7C)cycloalkyl(1-4C)alkyl, heterocyclyl(1-4C)alkyl, aryl(1-4C)alkyl, heteroaryl(1-4C)alkyl or NR6NR7N; wherein any alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, (3-7C)cycloalkyl(1- 4C)alkyl, heterocyclyl(1-4C)alkyl, aryl(1-4C)alkyl or heteroaryl(1-4C)alkyl, is optionally substituted by one or more substituents selected from halo, cyano, oxo, (1 -3C)alkyl, (2- 3C)alkenyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, aryl or heteroaryl, NRSCRSD, =CR6CR6D, OR6C, C(O)R6C, C(O)OR6C, C(O)N(R6D)R6C, N(R6D)C(O)R6C, SR6C, S(O)R6C, S(O)2R6c, S(O)2N(R6D)R6C or N(R6D)S(O)2R6C, (1-3C)alkyl, (1-3C)haloalkoxy); wherein R6c and RSD are each independently selected from hydrogen or (1 -3C)alkyl; wherein any (1 -3C)alkyl, (2-3C)alkenyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, aryl or heteroaryl substituent on group Z, including those in R6c and RSD, may be optionally further substituted by one or more substituents selected from halo, cyano, oxo, (1-3C)alkyl, (1-3C)haloalkyl, NRSERSF, OR6E, C(O)R6E, C(O)OR6E, OC(O)R6E, C(O)N(R6F)R6E, N(R6F)C(O)R6E, S(O)VR6E (where v is 0, 1 or 2), S(O)2N(R6F)R6E or N(R6F)S(O)2R6E; wherein R6E and RSF are each independently selected from hydrogen or (1 -3C)alkyl; wherein R6Nand R7Nare each independently selected from (1 -4C)alkyl or (3- 7C)cycloalkyl, wherein the (1 -4C)alkyl or (3-7C)cycloalkyl in R6Nand R7Nare optionally substituted with one of more substituents selected from halo, cyano, oxo, (1 -3C)alkyl, (2- 3C)alkenyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, aryl or heteroaryl, NRSGRSH, OR6G, C(O)R6G, C(O)OR6G, C(O)N(R6H)R6G, N(R6H)C(O)R6G, SR6G, S(O)R6G, S(O)2R6G, S(O)2N(R6H)R6G or N(R6H)S(O)2R6G; wherein R3H and R6c are each independently selected from hydrogen or (1 -3C)alkyl; i) with the proviso that: if R1 is a phenyl ring, then the phenyl ring comprises at least one substituent other than hydrogen in the ortho position; and ii) the compound is not:1 ,5-dimethyl-N-(2-methylbenzyl)-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;N-(2-methoxybenzyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H- pyrrole-2-carboxamideN-(2-chlorobenzyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide .2. A compound according to paragraph 1, or a pharmaceutically acceptable salt or solvate thereof, wherein LA is a linker group of the formula -[CRL1RL2]m- in which m is an integer selected from 1 or 2, and each occurrence of RL1and RL2are each independently selected from hydrogen or methyl.3. A compound according to paragraph 1 or paragraph 2, or a pharmaceutically acceptable salt or solvate thereof, wherein LA is a linker group of the formula -[CRL1RL2]-, wherein RL1and RL2are independently selected from hydrogen or methyl.3. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein LA is a linker group of the formula -[CH2]-.4. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is selected from phenyl, naphthyl or mono or bicyclic heteroaryl, each of which being optionally substituted by one or more substituents RIA, wherein each RIA is independently selected from halo, cyano or a group of the formula:-WA-WB-WC whereinWA is absent or (1-6C)alkylene;WB is absent or selected from -O-, -S-, -N(R1 B)-, -C(O)-, -C(O)O-, -OC(O)-, - C(O)N(R1 B)-, -N(R1 B)C(O)-, -S(O)-, -S(O)2-, -S(O)(=NR1 B)-, -S(O)2N(R1 B)- or N(R1 B)S(O)2; wherein R1 Bis selected from hydrogen or methyl;Wc is selected from hydrogen, (1-6C)alkyl), (3-6C)cycloalkyl or 4- to 6- membered heterocyclyl;wherein Wc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1-2C)alkyl, NR1cR1c, OR1c, C(O)R1c, C(O)N(R1 D)R1c, S(O)qR1c(where q is 0, 1 or 2), S(O)(=NR1 D)R1cor S(O)2N(R1 D)R1c; wherein R1cand R1care each independently selected from hydrogen, (1 -2C)alkyl or (3-6C)cycloalkyl, wherein any alkyl or cycloalkyl present in an optional substituent in a Wc group are each optionally substituted with one or more substituents selected from halo, cyano or NH2.5. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Ri is selected from phenyl, naphthyl or mono or bicyclic heteroaryl, each of which being optionally substituted by one or more substituents RIA, wherein each RIA is independently selected from halo, cyano or a group of the formula:-WA-WB-WC whereinWA is absent or (1-4C)alkylene;WB is absent or selected from -O-, -S-, -N(R1 B)-, -C(O)-, -C(O)O-, - C(O)N(R1 B)-, -N(R1 B)C(O)-, -S(O)-, -S(O)2-, -S(O)(=NR1 B)- or -S(O)2N(R1 B)-; wherein R1cis selected from hydrogen or methyl;Wc is selected from hydrogen, (1 -3C)alkyl), (3-6C)cycloalkyl 4- to 6- membered heterocyclyl; wherein Wc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1-2C)alkyl, NR1cR1 D, OR1c, C(O)R1c, C(O)N(R1c)R1c, S(O)qR1c(where q is 0, 1 or 2), S(O)(=NR1c)R1cor S(O)2N(R )R1c; wherein R1cand R1care each independently selected from hydrogen or (1 -2C)alkyl, wherein any alkyl present in an optional substituent in a Wc group are each optionally substituted with one or more halo substituents.6. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Ri is selected from phenyl, naphthyl or mono or bicyclic heteroaryl, each of which being optionally substituted by one or more substituents RIA, wherein each RIA is independently selected from halo, cyano or a group of the formula:-WA-WB-WC whereinWA is absent or (1-3C)alkylene;WB is absent or selected from -O-, -S-, -N(R1c)-, -C(O)-, -C(O)O-, - C(O)N(R1 B)-, -N(R1 B)C(O)-, -S(O)-, -S(O)2-, -S(O)(=NR1 B)- or -S(O)2N(RiB)-; wherein R1cis selected from hydrogen or methyl;Wc is selected from hydrogen, (1 -2C)alkyl), (3-4C)cycloalkyl or a 4-membered heterocyclyl; wherein Wc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, methyl, NR1cR1 D, OR1cor C(O)N(R1 D)R1c; wherein R1cand R1care each independently selected from hydrogen or methyl, wherein any alkyl present in an optional substituent in a Wc group are each optionally substituted with one or more halo substituents.7. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Ri is selected from phenyl, naphthyl or mono or bicyclic heteroaryl, each of which being optionally substituted by one or more substituents RIA, wherein each RIA is independently selected from halo, cyano or a group of the formula:-WA-WB-WC whereinWA is absent or (1-3C)alkylene;WB is absent or selected from -O-, -S-, -N(R1 B)-, -C(O)-, -C(O)O-, - C(O)N(R1 B)-, -N(R1 B)C(O)-, -S(O)-, -S(O)2-, -S(O)(=NR1 B)- or -S(O)2N(R1 B)-; wherein R1cis selected from hydrogen or methyl;Wc is selected from hydrogen or (1 -2C)alkyl); wherein the (1 -2C)alkyl) in the Wc group is optionally further substituted by one or more fluoro substituents.8. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Ri is selected from phenyl, naphthyl or mono or bicyclic heteroaryl, each of which being optionally substituted by one or more substituents RIA, wherein each RIA is independently selected from halo, cyano or a group of the formula:-WA-WB-WC whereinWA is absent or (1-3C)alkylene;WB is absent or selected from -O-, -S-, -N(R1 B)-, -C(O)-, -0(0)0-, - C(O)N(R1 B)- or -N(RiB)C(O)-; wherein R1 Bis selected from hydrogen or methyl;Wc is selected from hydrogen or (1 -2C)alkyl); wherein the (1 -2C)alkyl) in the Wc group is optionally further substituted by one or more fluoro substituents.9. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Ri is selected from phenyl, naphthyl, monocylic heteroaryl or bicyclic heteroaryl, each of which being optionally substituted by one or more substituents RIA, wherein each RIA is independently selected from fluoro, chloro, cyano, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2, OMe or OH. 10. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is selected fromwherein:RIN and R2N are selected from hydrogen or (1 -3C)alkyl; and each of R4, R5, Re, R7, Rs, R4p, Rsp, Rep, R7p, Rsp, R9, R10, R11 , R12, R13, R14, R15,R16,Ri7, R19, R20, R21, R22, R23, R24, R25, R26, R27 and R28 are independently selectedfrom hydrogen a group RIA, wherein each RIA is independently as defined in any one of the preceding paragraphs.11. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is: i) a group with a formula selected from:wherein:R4 is selected from hydrogen, halo (e.g. fluoro, chloro), cyano, (1 -3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH;Rs is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH;Re is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH;R7 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; andRs is selected from hydrogen, halo (e.g. fluoro, chloro), cyano, (1 -3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; ii) a group with the formula:wherein:R9is selected from hydrogen, halo (e.g. fluoro, chloro), cyano, (1-3C)alkyl, (1- 3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; R1cis selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; R11 is selected from hydrogen, halo, cyano, (1 -3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; RI2is selected from hydrogen, halo, cyano, (1 -3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; R11 is selected from hydrogen, halo, cyano, (1 -3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; R14 is selected from hydrogen, halo, cyano, (1 -3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; andRis is selected from hydrogen, halo, cyano, (1 -3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; iv) a group with a formula:wherein:R16 is selected from hydrogen, halo, cyano, (1 -3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; R17 is selected from hydrogen, halo, cyano, (1 -3C)alkyl, (1-3C)haloalkyl (e.g. CF3,CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; R19 is selected from hydrogen, halo, cyano, (1 -3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; R2O is selected from hydrogen, halo, cyano, (1 -3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH;R2I is selected from hydrogen, halo, cyano, (1 -3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; R22is selected from hydrogen, halo, cyano, (1 -3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; v) a group with a formula selected from:wherein:R23 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; R24 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; R25 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3,CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; R26 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; R27 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH;R28 is selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH;RIN is selected from hydrogen or (1-4C)alkyl; and R2N is selected from hydrogen or (1 -4C)alkyl.12. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is: i) a group with a formula selected from:wherein:R4 is selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g.CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F) or OMe;Rs is selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2or OMe;Re is selected from hydrogen, halo, methyl or NH2;R7 is selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2or OMe; andRs is selected from hydrogen, halo (e.g. fluoro, chloro), cyano, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F) NH2or OMe; ii) a group with the formula:wherein:R4pis selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F) or OMe; R8Pis selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2, OMe;RePis selected from hydrogen, halo, methyl, or NH2;R7Pis selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2, OMe; and Rsp is selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g.CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F) or OMe. iii) a group with a formula selected from:wherein:R9is selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy or OMe; R1cis selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), NH2, or OH;R11 is selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), NH2or OH;R12 is selected from hydrogen, halo or methyl;R13 is selected from hydrogen, halo or methyl;R14 is selected from hydrogen, halo, or methyl; andR15 is selected from hydrogen, halo or methyl; iv) a group with a formula:wherein:R16 is selected from hydrogen, halo, cyano, methyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F); R17 is hydrogen;R19 is hydrogen;R2O is hydrogen;R2I is hydrogen; andR22is hydrogen; v) a group with a formula selected from:wherein:R23 is selected from hydrogen, halo, methyl or (1-3C)haloalkyl;R24 is hydrogen;R25 is selected from hydrogen or NH2;R26 is hydrogen;R27 is hydrogen;R28 is hydrogen;RIN is selected from hydrogen or methyl; andR2N is selected from hydrogen or methyl.13. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Ri is: i) a group with the formula:wherein:R4 is selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g.CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F) or OMe;Rs is selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2or OMe;Re is selected from hydrogen, halo, methyl or NH2;R7 is selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2or OMe; andRs is selected from hydrogen, halo (e.g. fluoro, chloro), cyano, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F) NH2or OMe; ii) a group with the formula:wherein:R4pis selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g.CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F) or OMe; R8Pis selected from hydrogen, fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2or OMe;RePis selected from hydrogen, or NH2;R7Pis selected from hydrogen, fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2or OMe; andRsp is selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F) or OMe; optionally wherein at least one of R4pand R8Pis not hydrogen; iii) a group with a formula selected from:wherein:R9is selected from hydrogen, halo (e.g. fluoro, chloro), methyl or fluoromethyl (e.g. CF3, CHF2or CH2F);R10 is selected from hydrogen or NH2;R11 is selected from hydrogen, NH2or OH;RI2is hydrogen;R13 is selected from hydrogen or methyl; R14 is selected from hydrogen or methyl; andR15 is hydrogen.14. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Ri is: i) a group with a formula selected from:wherein:R4 is selected from hydrogen, halo or methyl;is selected from hydrogen or NH2; is hydrogen; and is hydrogen;wherein: is selected from hydrogen or fluoro; is hydrogen; is hydrogen; is hydrogen; and is selected from hydrogen or methoxy;wherein at least one of R4pand R8Pis not hydrogen;wherein:R9 is selected from hydrogen, fluoro or chloro;R10 is hydrogen;R11 is selected from hydrogen or NH2;R12 is hydrogen;R13 is selected from hydrogen or methyl;R14 is hydrogen; andR15 is hydrogen.14. A compound according to any one of the preceding paragraphs, wherein if R1 isthen at least one of R4Pand R8Pis not hydrogen, preferably both of R4Pand R8Pare not hydrogen.15. A compound according to any one of paragraph 1 to 12, or a pharmaceutically acceptable salt or solvate thereof, wherein: i) R1 is:wherein R4 is selected from hydrogen or halo; and Rs is selected from hydrogen or methoxy; ii) R1 is:wherein R4 is selected from hydrogen or halo; iii) R1 is:wherein R4 is selected from hydrogen, methyl or halo; and R7 is selected from hydrogen or NH2; iv) R1 is:wherein R7 is selected from hydrogen or NH2and Rs is selected from hydrogen or methyl; v) R1 iswherein R9is selected from hydrogen, fluoro, methyl or fluromethyl (e.g. CHF2); and R11 is selected from hydrogen or NH2; vi) Ri iswherein R9is selected from hydrogen, fluoro, methyl or fluromethyl (e.g. CHF2); and R11 is selected from hydrogen or NH2; vii) Ri is:wherein R9is selected from hydrogen, fluoro, methyl or fluromethyl (e.g. CHF2); andR11 is selected from hydrogen or NH2; or viii) Ri is:wherein R9is selected from hydrogen, fluoro, methyl or fluromethyl (e.g. CHF2); and R11 is selected from hydrogen or NH2.16. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein R2 is selected from hydrogen or (1-3C)alkyl.17. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein R2 is selected from hydrogen or methyl.18. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein R2 is hydrogen.19. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is selected from:wherein:Xi is selected from O, S, N or N RXI N;X2 is selected from CRX2, O, S, N or N RX2N; wherein:RX2is selected from hydrogen, (1 -3C)alkyl or (3-6C)cycloalkyl, wherein the (1- 3C)alkyl or (3-6C)cycloalkyl is optionally substituted by one or more substituents selected from halo, cyano, (1-2C)alkoxy or hydroxy;RXI N and RX2N are independently selected from hydrogen, (1 -3C)alkyl or (3- 6C)cycloalkyl, each of which being optionally substituted by one or more halo substituents; andRsx and Rsyare as defined in any one of the preceding paragraphs;Yi is selected from CRY1or N;Y2 is selected from CRY2or N; wherein each of RY1, RY2and RY3are independently selected from hydrogen, (1- 3C)alkyl or (3-6C)cycloalkyl, wherein the (1 -3C)alkyl or (3-6C)cycloalkyl is optionally substituted by one or more substituents selected from halo, cyano, (1-2C)alkoxy or hydroxy; andRsx and Rsyare as defined in paragraph 1.20. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is selected from:wherein:Xi is selected from O, S, or N RXI N ; wherein RXI N is selected from hydrogen or (1 -3C)alkyl, wherein the alkyl is optionally substituted by one or more halo substituents; andX2 is selected from CRx2, O, S or N; wherein RX2is selected from hydrogen or methylY1 is selected from CRY1or N;Y2 is selected from CRY2or N; wherein each of RY1and RY2are independently selected from hydrogen or methyl; andRsx and Rsyare as defined in paragraph 1.21 . A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is selected from:wherein:Xi is selected from O, S, or NRXIN ; wherein RXIN is selected from hydrogen or (1- 3C)alkyl, wherein the alkyl is optionally substituted by one or more fluoro substituents X2 is selected from CRx2 or N; wherein RX2is selected from hydrogen or (1 -3C)alkyl, wherein the alkyl is optionally substituted by one or more fluoro substituents;Y1 is selected from CRYI or N; wherein RY1is selected from hydrogen or (1 -3C)alkyl, wherein the alkyl is optionally substituted by one or more fluoro substituents; andRsx and Rsyare each as defined in paragraph 1.22. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is selected from:wherein: Xi is selected from NRXIN; wherein RXIN is selected from hydrogen or (1 -3C)alkyl optionally substituted by one or more fluoro substituents;X2 is selected from CRx2 or N; wherein RXIN is selected from hydrogen, methyl or ethyl; andRsx and Rsyare as defined in paragraph 1.23. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is :wherein: Xi is selected from N RXI N; wherein RXI N is selected from hydrogen or (1 -3C)alkyl optionally substituted by one or more fluoro substituents;X2 is selected from CRx2 or N; wherein RXI N is selected from hydrogen, methyl or ethyl;Rsx is as defined in paragraph 1. 24. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is selected from:wherein RXI N is selected from hydrogen, methyl or ethyl, wherein the methyl and ethyl are optionally substituted by one or more fluoro substituents; and Rsx is as defined in paragraph 1.25. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is:wherein RXIN is selected from hydrogen, methyl or ethyl, wherein the methyl and ethyl are optionally substituted by one or more fluoro substituents; andR3xis as defined in paragraph 1.26. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Rsx and Rsyare selected from halo, cyano, or a group of the formula:-XA-XB-XC wherein:XA is absent or (1-4C)alkylene;XB is absent or selected from -O-, -S-, -N(RSA)-, -C(O)-, -C(O)O-, -OC(O)- or - N(RSA)C(O)-; wherein RSA is selected from hydrogen or (1 -2C)alkyl;Xc is selected from hydrogen, (1 -6C)alkyl), (3-6C)cycloalkyl or heterocyclyl; wherein Xc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1-4C)alkyl, NRSBRSC, ORSB, C(O)RSB, C(O)ORSB, OC(O)RSB, C(O)N(R3C)R3B; wherein R3B and R3c are each independently selected from hydrogen, (1-3C)alkyl or (3-6C)cycloalkyl, wherein (1 -3C)alkyl or (3- 6C)cycloalkyl are each optionally substituted with one or more substituents selected from halo, cyano, hydroxy or NH2.27. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Rsx and Rsyare selected from halo, cyano, or a group of the formula:-XA-XB-XC wherein:XA is absent;XB is absent, -0-, or -N(RsA)-;Xc is selected from (1 -6C)alkyl) or (3-6C)cycloalkyl; wherein Xc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1-4C)alkyl, NRSBRSC, ORSB, C(O)RSB, C(O)ORSB, OC(O)RSB, C(O)N(R3C)R3B; wherein R3B and R3c are each independently selected from hydrogen or (1 -2C)alkyl.28. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Rsx and Rsyare selected from halo, cyano, or a group of the formula:-XA-XB-XC wherein:XA is absent;XB is absent;Xc is selected from (1 -3C)alkyl) or (3-6C)cycloalkyl; wherein Xc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1 -2C)alkyl, NRSBRSC or ORSB; wherein RSB and Rsc are each independently selected from hydrogen or methyl.29. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Rsx and Rsyare selected from halo, cyano, (1 -2C)alkyl cyclopropyl, wherein any (1 -2C)alkyl or cyclopropyl in a Rsx or Rsygroup is optionally further substituted by one or more substituents selected from halo or cyano.30. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Rsx and Rsyare selected from fluoro, chloro, bromo, cyano, methyl or cyclopropyl, wherein methyl or cyclopropyl are optionally substituted by one or more fluoro substituents.31. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Z is selected from (1 -4C)alkyl, (3-12C)cycloalkyl, heterocyclyl, phenyl, heteroaryl or NR6NR7N, wherein any (1-4C)alkyl, (3-12C)cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally substituted by one or more substituents selected from halo, cyano, oxo, (1-3C)alkyl, (2-3C)alkenyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, aryl, heteroaryl, NRBCRSD, =CR6CR6D, ORBC, C(O)RBC, C(O)ORBC, C(O)N(R6D)R6C, N(R6D)C(O)R6C, SRBC, S(O)R6c or S(O)2R6c; wherein R6c and RBD are each independently selected from hydrogen or (1-3C)alkyl; wherein any (1 -3C)alkyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, aryl or heteroaryl substituent on group Z, including R6c and RBD, is optionally further substituted by one or more substituents selected from halo, cyano, oxo, (1-3C)alkyl, (1-3C)haloalkyl, NRBERSF, ORGE, C(O)RGE, C(O)ORBE or OC(O)RBE; wherein RGE and RGF are each independently selected from hydrogen or (1 -3C)alkyl; and wherein R6Nand R7Nare each independently selected from hydrogen, (1 -4C)alkyl or (3-6C)cycloalkyl; wherein R6Nand R7Nare each independently selected from (1 -4C)alkyl or (3-7C)cycloalkyl, wherein the (1 -4C)alkyl or (3-7C)cycloalkyl in R6Nand R7Nare optionally substituted with one of more substituents selected from halo, cyano, oxo, (1 -3C)alkyl, (2- 3C)alkenyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, aryl or heteroaryl, NRGGR6H, OR6G, C(O)R6G, C(O)OR6G, C(O)N(R6H)R6G, N(R6H)C(O)R6G, SR6G, S(O)R6G, S(O)2R6G, S(O)2N(R6H)R6G or N(R6H)S(O)2R6G; wherein Ren and R6c are each independently selected from hydrogen or (1 -3C)alkyl.32. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Z is selected from (3- 12C)cycloalkyl, a 4- to 12-membered heterocyclic ring (including fused, bridged and spirocyclic heterocyclic rings), phenyl, mono- or bicyclic heteroaryl or NR6NR7N; wherein any (3-12C)cycloalkyl, a 4- to 12-membered heterocyclic ring, phenyl or mono- or bicyclic heteroaryl ring may be optionally substituted by one or more substituents selected from halo, cyano, oxo, (1-3C)alkyl, (2-3C)alkenyl, (3-6C)cycloalkyl, 4- to 7- membered heterocyclyl, phenyl, 5- or 6-membered heteroaryl, NRBCRSD, OR6c, C(O)R6c, C(O)OR6c, C(O)N(RGD)R6C, N(RBD)C(O)RBC, SR6c, S(O)R6c or S(O)2R6ci wherein R6c and RBD are each independently selected from hydrogen or (1 -3C)alkyl; wherein any (1 -3C)alkyl, (2-3C)alkenyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl present in a substituent on group Z, including those in R6c and RBD, is optionally further substituted by one or more substituents selected from halo, cyano, oxo, (1-3C)alkyl, (1-3C)haloalkyl, NRBERSF, ORGE, C(O)RGE, C(O)ORGE or OC(O)RGE; wherein RGE and RBF are each independently selected from hydrogen or (1 -3C)alkyl; wherein R6Nand R7Nare each independently selected from (1 -4C)alkyl which is optionally substituted by one or more substituents selected from halo, cyano, oxo, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, NRBGRSH, ORBG, C(0)R6G, C(0)0R6G, C(O)N(R6H)R6G, N(R6H)C(O)R6G, SR6G, S(O)RBG or S(O)2RSG; wherein R6G and R6H are each independently selected from hydrogen or (1 -3C)alkyl.33. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Z is selected from (3- 12C)cycloalkyl, a 4- to 12-membered heterocyclic ring (including fused, bridged and spirocyclic heterocyclic rings), phenyl, mono- or bicyclic heteroaryl or NR6NR7N; wherein any (3-12C)cycloalkyl, a 4- to 12-membered heterocyclic ring, phenyl or mono- or bicyclic heteroaryl ring may be optionally substituted by one or more substituents selected from halo, cyano, oxo, (1-3C)alkyl, (1-3C)alkenyl, (3-4C)cycloalkyl, 5-membered heteroaryl, NRBCRSD,=CR6cR6D, ORBC, C(O)RBC, C(O)ORBC, C(O)N(R6D)R6C,N(R6D)C(O)R6C, SR6c or S(O)2R6c; wherein R6c and RBD are each independently selected from hydrogen or (1-3C)alkyl; wherein any (1 -3C)alkyl, (1-3C)alkenyl, (3-4C)cycloalkyl, 5-membered heteroaryl, present in a substituent on group Z, including those in R6c and RBD, is optionally further substituted by one or more substituents selected from halo, cyano, oxo, NRBERSF, ORGE, C(O)RGE, C(O)ORBE or OC(O)RBE; wherein RGE and RGF are each independently selected from hydrogen or (1 -3C)alkyl; wherein R6Nand R7Nare each independently selected from (1 -4C)alkyl which is optionally substituted by one or more substituents selected from halo, cyano, oxo, (3- 6C)cycloalkyl, 4- to 7-membered heterocyclyl, NRGGR6H, ORGG, C(O)RGG, C(O)ORBG, C(O)N(R6H)R6G or N(R6H)C(O)R6G; wherein R6c and Ren are each independently selected from hydrogen or (1 -2C)alkyl.34. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Z is selected from (3- 8C)cycloalkyl, a 4- to 12-membered nitrogen linked heterocyclic ring (including fused, bridged and spirocyclic heterocyclic rings), phenyl, mono- or bicyclic heteroaryl or NR6NR7N; wherein any (3-8C)cycloalkyl, 4- to 12-membered nitrogen linked heterocyclic ring, phenyl or mono- or bicyclic heteroaryl may be optionally substituted by one or more substituents selected from halo, cyano, oxo, (1-3C)alkyl, (3-4C)cycloalkyl, 5-membered heteroaryl, NRSCRSD, =CR6CR6D, OR6c, C(O)R6c, C(O)OR6c, C(O)N(RBD)R6C, N(RBD)C(O)RBC, SR6c or S(O)2R6c; wherein R6c and RBD are each independently selected from hydrogen or (1- 3C)alkyl; wherein any (1 -3C)alkyl, (3-4C)cycloalkyl or 5-membered heteroaryl present substituent on group Z, including those in R6c and RBD, is optionally further substituted by one or moresubstituents selected from halo, cyano, oxo, NRSERSF, ORSE, C(O)RSE, C(O)ORSE or OC(O)R6E; wherein RSE and RSF are each independently selected from hydrogen or (1- 3C)alkyl; wherein R6Nand R7Nare each independently selected from (1 -4C)alkyl which is optionally substituted by one or more substituents selected from halo, cyano, oxo, (3- 6C)cycloalkyl, NRSGRSH, ORSG or C(O)R6G; wherein R6c and RSH are each independently selected from hydrogen or (1 -2C)alkyl.35. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Z is selected from (3- 8C)cycloalkyl, 5- to 12-membered nitrogen linked mono- or bicyclic heterocyclic ring (including fused, bridged and spirocyclic heterocyclic rings), phenyl, mono- or bicyclic heteroaryl (including partially aromatic bicyclic heteroaryls) or NR6NR7N; wherein any (3-8C)cycloalkyl, a 5- to 12-membered nitrogen linked mono- or bicyclic heterocyclic ring (including fused, bridged and spirocyclic heterocyclic rings), phenyl or mono- or bicyclic heteroaryl may be optionally substituted by one or more substituents selected from halo, cyano, oxo, (1-3C)alkyl, (1-3C)alkenyl, (3-4C)cycloalkyl, 5-membered heteroaryl, NR6CR6D, =CR6cR6D, OR6c, SR6c or S(O)2R6c; wherein R6c and R6D are independently selected from hydrogen or methyl; wherein any (1 -3C)alkyl substituent on group Z, including those in R6c and RSD, is optionally further substituted by one or more substituents selected from halo, cyano, oxo, NRSERSF or ORSE; wherein RSE and RSF are each independently selected from hydrogen or (1 -2C)alkyl; wherein R6Nand R7Nare each independently selected from (1 -4C)alkyl which is optionally substituted by (3-4C)cycloalkyl.36. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Z is selected from (3- 7C)cycloalkyl, 5- to 6-membered nitrogen linked monocyclic saturated or partially saturated heterocyclyl, 4- to 10-membered nitrogen linked fused bicyclic heterocyclyl (including saturated or partially saturated ring systems), 4- to 10-membered nitrogen linked spirocyclic bicyclic heterocyclyl, phenyl, mono- or bicyclic heteroaryl (including partially aromatic heteroaryl e.g. a 4- to 10-membered nitrogen linked heterocylic ring fused to an aromatic or heteroaromatic ring) or NR6NR7N; wherein any (3-7C)cycloalkyl, 5- to 6-membered nitrogen linked monocyclic saturated or partially saturated heterocyclyl, 4- to 10-membered nitrogen linked fusedbicyclic heterocyclyl, 4- to 10-membered nitrogen linked spirocyclic bicyclic heterocyclyl, 4- to 10-membered nitrogen linked fused bicyclic heterocylic ring comprising a non-aromatic heterocyclic ring fused to an aromatic or heteroaromatic ring, phenyl or mono- or bicyclic heteroaryl, may be optionally substituted by one or more substituents selected from halo, cyano, oxo, methyl, =CH2, cyclopropyl, 5-membered heteroaryl, NH2, methoxy, hydroxymethyl, OH, fluoromethoxy, fluoromethyl (e.g. CF3, CHF2 or CH2F), S-CH3 or S(O)2CH3; wherein R6Nis (1 -2C)alkyl and R7Nis (1 -2C)alkyl which is optionally substituted by (3- 4C)cycloalkyl.37. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, wherein Z is selected from 5- to 6- membered monocyclic heterocyclyl, a 4- to 10-membered nitrogen-linked bicyclic heterocylic ring fused to an aromatic or heteroaromatic ring, phenyl or NR6NR7N; wherein the 5- to 6-membered monocyclic heterocyclyl or 4- to 10-membered fused bicyclic ring comprising a non-aromatic ring fused to an aromatic ring may be optionally substituted by one or more substituents selected from fluoro, chloro, cyano, oxo, methyl, =CH2, NH2, methoxy, hydroxy(1-2C) alkyl, OH, fluoromethoxy, fluoromethyl (e.g. CF3, CHF2 or CH2F) or S-CH3; wherein R6Nis (1 -2C)alkyl and R7Nis (1 -2C)alkyl which is optionally substituted by (3-4C)cycloalkyl.38. A compound according to any one of paragraphs 1 to 34, or a pharmaceutically acceptable salt or solvate thereof, wherein Z has a structure selected from:wherein any of the group Z rings above may be substituted on an available carbon atom by one or more substituents as defined in any one of the preceding paragraphs; and R6Nand R7Nare as defined in any one of the preceding paragraphs;Rzi is selected from hydrogen or (1 -2C)alkyl;RZ2 is selected from hydrogen or (1 -2C)alkyl;Rzs is selected from hydrogen or (1 -2C)alkyl;RZ4 is selected from hydrogen or (1 -2C)alkyl;Rzs is selected from hydrogen or (1 -2C)alkyl;Rze is selected from hydrogen or (1 -2C)alkyl;Rz? is selected from hydrogen or (1 -2C)alkyl;Rzs is selected from hydrogen or (1 -2C)alkyl;Rzg is selected from hydrogen or (1 -2C)alkyl;Rz is selected from hydrogen or (1 -2C)alkyl; andRzn is selected from hydrogen or (1 -2C)alkyl; optionally wherein the group Z rings above may be substituted on an available carbon atom by one or more substituents selected from halo, cyano, oxo, (1 -3C)alkyl, =CR6cR6D, (2-3C)alkenyl, (3-6C)cycloalkyl, 5-membered heteroaryl, (1-3C)haloalkyl, N RSCRSD, OR6c, SR6c, S(O)R6c orS(O)2R6c; wherein R6c is selected from hydrogen or (1- 2C)alkyl;wherein any (1 -3C)alkyl substituent on the ring above is optionally further substituted by one or more substituents selected from halo, cyano, oxo, (1 -3C)alkyl, (1-3C)haloalkyl, N RSERSF or ORSE; wherein RSE and RSF are each independently selected from hydrogen or methyl; and R6Nand R7Nare each independently selected from (1 -4C)alkyl which is optionally substituted by (3-4C)cycloalkyl.39. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt or solvate thereof, having the structural formula (la):wherein Ri, RXIN, RSX and Z are as defined in any one of the preceding paragraphs.40. A compound selected from:4-(3-azabicyclo[3.1 ,0]hexan-3-ylsulfonyl)-1 ,5-dimethyl-N-(5-quinolylmethyl)pyrrole-2- carboxamide;4-[[3-(hydroxymethyl)-1-piperidyl]sulfonyl]-1,5-dimethyl-N-(5-quinolylmethyl)pyrrole-2- carboxamide;4-(azepan-1-ylsulfonyl)-1 ,5-dimethyl-N-(2-methylbenzyl)-1 H-pyrrole-2-carboxamide;4-((3-azabicyclo[4.1 ,0]heptan-3-yl)sulfonyl)-1 ,5-dimethyl-N-(2-methylbenzyl)-1 H-pyrrole-2- carboxamide;4-((3,4-dihydroisoquinolin-2(1 H)-yl)sulfonyl)-1 ,5-dimethyl-N-(2-methylbenzyl)-1 H-pyrrole-2- carboxamide;4-((4-hydroxypiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(2-methylbenzyl)-1 H-pyrrole-2- carboxamide;5-bromo-1-methyl-4-[(4-methyl-1-piperidyl)sulfonyl]-N-(5-quinolylmethyl)pyrrole-2- carboxamide;5-cyano-1-methyl-4-[(4-methyl-1-piperidyl)sulfonyl]-N-(5-quinolylmethyl)pyrrole-2- carboxamide;5-cyclopropyl-1-methyl-4-[(4-methyl-1-piperidyl)sulfonyl]-N-(5-quinolylmethyl)pyrrole-2- carboxamide;1.5-dimethyl-4-[(4-methyl-1-piperidyl)sulfonyl]-N-(4-quinolylmethyl)pyrrole-2-carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(naphthalen-1-ylmethyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-[(4-methyl-1-piperidyl)sulfonyl]-N-(8-quinolylmethyl)pyrrole-2-carboxamide;N-(5-isoquinolylmethyl)-1 ,5-dimethyl-4-[(4-methyl-1-piperidyl)sulfonyl]pyrrole-2-carboxamide;N-(4-isoquinolylmethyl)-1 ,5-dimethyl-4-[(4-methyl-1-piperidyl)sulfonyl]pyrrole-2-carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;N-((1 H-indol-7-yl)methyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-((3-methylpyridin-4-yl)methyl)-1 H-pyrrole-2-carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(2-(trifluoromethoxy)benzyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-((4-methylpyridin-3-yl)methyl)-1 H-pyrrole-2-carboxamide;1.5-dimethyl-N-((1-methyl-1 H-indol-4-yl)methyl)-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(quinoxalin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(pyrazolo[1 ,5-a]pyridin-4-ylmethyl)-1 H- pyrrole-2-carboxamide;N-(2-fluoro-6-methoxybenzyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;N-(3-amino-2-chlorobenzyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl) sulfonyl)- 1 H-pyrrole-2- carboxamide;4-[(4-hydroxypiperidin-1-yl)sulfonyl]-1 ,5-dimethyl-N-[(quinoline-5-yl)methyl]-1 H-pyrrole-2- carboxamide;1.5-dimethyl-N-[(quinoline-5-yl)methyl]-4-(1 ,2,3,4-tetrahydroisoquinoline-2-sulfonyl)-1 H- pyrrole-2-carboxamide;1.5-dimethyl-N-[(quinoline-5-yl)methyl]-4-{[4-(trifluoromethyl)piperidin-1 -yl]sulfonyl}-1 H- pyrrole-2-carboxamide;1.5-dimethyl-4-[(4-methylpiperidin-1-yl)sulfonyl]-N-[(quinolin-6-yl)methyl]-1H-pyrrole-2- carboxamide;4-(2,3-dihydro-1H-indole-1-sulfonyl)-1,5-dimethyl-N-[(quinolin-5-yl)methyl]-1H-pyrrole-2- carboxamide; give 4-[[4-(hydroxymethyl)-1-piperidyl]sulfonyl]-1,5-dimethyl-N-(6-quinolylmethyl)pyrrole-2- carboxamide;4-(3,4-dihydro-1H-2,6-naphthyridin-2-ylsulfonyl)-1,5-dimethyl-N-(5-quinolylmethyl)pyrrole-2- carboxamide;4-(6-azaspiro[3.4]octan-6-ylsulfonyl)-1,5-dimethyl-N-(5-quinolylmethyl)pyrrole-2- carboxamide;4-(3,4-dihydro-1 H-pyrrolo[1 ,2-a]pyrazin-2-ylsulfonyl)-1 ,5-dimethyl-N-(5- quinolylmethyl)pyrrole-2-carboxamide;4-(3,4-dihydro-1H-2,7-naphthyridin-2-ylsulfonyl)-1,5-dimethyl-N-(5-quinolylmethyl)pyrrole-2- carboxamide;1.5-dimethyl-4-(3-methylpyrrolidin-1-yl)sulfonyl-N-(5-quinolylmethyl)pyrrole-2-carboxamide;1.5-dimethyl-4-morpholinosulfonyl-N-(5-quinolylmethyl)pyrrole-2-carboxamide;4-[(4-fluoro-1-piperidyl)sulfonyl]-1,5-dimethyl-N-(5-quinolylmethyl)pyrrole-2-carboxamide;4-(((3S,4S)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)- 1 H-pyrrole-2-carboxamide;4-{[(3R,4R)-4-hydroxy-3-methylpiperidin-1-yl]sulfonyl}-1 ,5-dimethyl-N-[(quinolin-5-yl)methyl]-1 H-pyrrole-2-carboxamide;4-(((3S,4R)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide4-{[(3R,4S)-4-hydroxy-3-methylpiperidin-1-yl]sulfonyl}-1,5-dimethyl-N-[(quinolin-5-yl)methyl]-1 H-pyrrole-2-carboxamide;4-[(7-hydroxy-3,4-dihydro-1H-isoquinolin-2-yl)sulfonyl]-1 ,5-dimethyl-N-(5- quinolylmethyl)pyrrole-2-carboxamide;1.5-dimethyl-N-(5-quinolylmethyl)-4-(1 ,4,6,7-tetrahydropyrrolo[3,2-c]pyridin-5- ylsulfonyl)pyrrole-2-carboxamide;4-((6,7-dihydroisoxazolo[4,5-b]pyridin-4(5H)-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-((5-fluoroisoindolin-2-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;4-(isoindolin-2-ylsulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1H-pyrrole-2-carboxamide;4-(((3S,4S)-3-fluoro-4-methylpiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1H- pyrrole-2-carboxamide;4-(((3R,4R)-3-fluoro-4-methylpiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1H- pyrrole-2-carboxamide;1.5-dimethyl-4-((4-methyl-3,6-dihydropyridin-1 (2H)-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;1-ethyl-5-methyl-N-(2-methylbenzyl)-4-((4-methylpiperidin-1-yl)sulfonyl)-1H-pyrrole-2- carboxamide;N-((7-aminoquinazolin-5-yl)methyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H- pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-(2-chloro-6-methoxybenzyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;N-(2-methoxy-6-methylbenzyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-((6-methylquinolin-5-yl)methyl)-1H- pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-(benzo[d]thiazol-7-ylmethyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H-pyrrole-2- carboxamide;N-(2-chloro-6-(trifluoromethoxy)benzyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H- pyrrole-2-carboxamide;N-((4-aminonaphthalen-1-yl)methyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;N-(5-amino-2-chlorobenzyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;4-((4-hydroxypiperidin-1-yl)sulfonyl)-N-(2-methoxy-6-(trifluoromethyl)benzyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-4-((4-hydroxypiperidin-1-yl)sulfonyl)-1,5-dimethyl-1H- pyrrole-2-carboxamide;N-(2-chloro-6-(difluoromethoxy)benzyl)-4-((4-hydroxypiperidin-1-yl)sulfonyl)-1,5-dimethyl-1H- pyrrole-2-carboxamide;5-chloro-1-methyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;(S)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(1-(quinolin-5-yl)ethyl)-1 H-pyrrole-2- carboxamide;(R)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(1-(quinolin-5-yl)ethyl)-1 H-pyrrole-2- carboxamide;N-((6-chloroquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((4-methyl-3-oxopiperazin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;N-((8-hydroxyquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-(3-amino-2-methylbenzyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;N-(3-amino-2-methoxybenzyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-((4-methylcyclohexyl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((1 ,4,6,7-tetrahydro-5H-pyrazolo[4,3- c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-(2-fluoro-6-methoxybenzyl)-1 ,5-dimethyl-4-((1 ,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-1 ,5-dimethyl-4-((1 ,4,6,7-tetrahydro-5H- pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-1 ,5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-1 H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-1.5-dimethyl-1 H-pyrrole-2-carboxamide;4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-N-(2-fluoro-6-methoxybenzyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;4-(6,7-dihydro-4H-pyrazolo[1 ,5-a]pyrazin-5-ylsulfonyl)-N-[(6-fluoroquinoxalin-5-yl)methyl]-1.5-dimethyl-pyrrole-2-carboxamide;N-[(2-amino-3-methyl-4-pyridyl)methyl]-4-(6,7-dihydro-4H-pyrazolo[1 ,5-a]pyrazin-5- ylsulfonyl)-1 ,5-dimethyl-pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-1 .5-dimethyl-1 H- pyrrole-2-carboxamide;4-((3,4-dihydro-2,6-naphthyridin-2(1 H)-yl)sulfonyl)-1 ,5-dimethyl-N-((2-methylquinazolin-5- yl)methyl)-1 H-pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-4-((3,4-dihydro-2,6-naphthyridin-2(1 H)-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;5-chloro-4-((6,7-dihydropyrazolo[1,5-a]pyrazin-5(4H)-yl)sulfonyl)-N-(2-fluoro-6- methoxybenzyl)-1-methyl-1 H-pyrrole-2-carboxamide;5-chloro-4-(6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-ylsulfonyl)-N-[(6- fluoro- 5- quinolyl)methyl]-1-methyl-pyrrole-2-carboxamide;5-chloro-N-((6-fluoroquinolin-5-yl)methyl)-4-((4-hydroxypiperidin-1-yl)sulfonyl)-1-methyl-1 H- pyrrole-2-carboxamide;5-chloro-4-(2,3-dihydropyrrolo[3,2-b]pyridin-1-ylsulfonyl)-N-[(6-fluoro-5-quinolyl)methyl]-1- methyl-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-1,5-dimethyl-4-(phenylsulfonyl)-1H-pyrrole-2- carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-4-((4-chlorophenyl)sulfonyl)-1,5-dimethyl-1H- pyrrole-2-carboxamide;4-((3,4-dihydroisoquinolin-2(1 H)-yl)sulfonyl)-N-(imidazo[1 ,2-a]pyridin-5-ylmethyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-4-((3,4-dihydroisoquinolin-2(1H)-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-4-((7-fluoro-3,4-dihydroisoquinolin-2(1H)- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;4-((3-hydroxy-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((TRANS)-3,4-dimethylpyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;4-((5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((3S,4S)-3-fluoro-4-methylpyrrolidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;4-(((3R,4R)-3-fluoro-4-methylpyrrolidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;(R)-1,5-dimethyl-4-((3-methylpiperidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;1,5-dimethyl-4-((3-methylenepyrrolidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1H-pyrrole-2- carboxamide;(R)-4-((3,3-difluoro-4-methylpyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;(S)-4-((3,3-difluoro-4-methylpyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;1.5-dimethyl-4-((3-(methylthio)azetidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;(S)-1 ,5-dimethyl-4-((3-methylpiperidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;4-(((3S,4R)-3-fluoro-4-hydroxypiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((3R,4S)-3-fluoro-4-hydroxypiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((1 R,5R)-1 -cyano- 3-azabicyclo[3.1.0]hexan-3-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5- ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((1S,5S)-1-cyano-3-azabicyclo[3.1.0]hexan-3-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5- ylmethyl)-1 H-pyrrole-2-carboxamide;4-((6,7-dihydro-[1 ,2,3]triazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5- ylmethyl)-1 H-pyrrole-2-carboxamide;1.5-dimethyl-4-((2-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;(S)-4-((3-cyclopropylpyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole- 2-carboxamide(R)-4-((3-cyclopropylpyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole- 2-carboxamide4-((2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;(R)-1 ,5-dimethyl-4-((3-(methylsulfonyl)pyrrolidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;1.5-dimethyl-N-(quinolin-5-ylmethyl)-4-((2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5- yl)sulfonyl)-1 H-pyrrole-2-carboxamide;(R)-4-((3-(1 H-pyrazol-4-yl)pyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;(S)-4-((3-(1 H-pyrazol-4-yl)pyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;4-((3,3-difluoropiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;4-((6-hydroxy-3-azabicyclo[3.1 ,0]hexan-3-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;1.5-dimethyl-4-((3-methyl-2,5-dihydro-1 H-pyrrol-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;4-(((3S,4R)-3-methoxy-4-methylpiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide4-(((3R,4S)-3-methoxy-4-methylpiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide(S)-1,5-dimethyl-4-((7-methyl-6,7-dihydropyrazolo[1,5-a]pyrazin-5(4H)-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((2R,4S)-4-hydroxy-2-methylpyrrolidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;(S)-4-((8-hydroxy-5-azaspiro[2.5]octan-5-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;(R)-4-((8-hydroxy-5-azaspiro[2.5]octan-5-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;1.5-dimethyl-4-((3-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;1.5-dimethyl-N-(quinolin-5-ylmethyl)-4-((3-(trifluoromethyl)-2,5-dihydro-1H-pyrrol-1- yl)sulfonyl)-1H-pyrrole-2-carboxamide;4-((7,7-difluoro-3-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-1,5- dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-((6-(hydroxymethyl)-3-azabicyclo[3.1.0]hexan-3-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5- ylmethyl)-1H-pyrrole-2-carboxamide;4-(((3S,4S)-3-fluoro-4-hydroxypiperidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((S)-3-((R)-1-hydroxyethyl)pyrrolidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((S)-3-((S)-1-hydroxyethyl)pyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((R)-3-((S)-1-hydroxyethyl)pyrrolidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((R)-3-((R)-1-hydroxyethyl)pyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-((2,3-dihydro-1 H-pyrrolo[3,2-b]pyridin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-((2,3-dihydro-1 H-pyrrolo[3,2-b]pyridin-1 -yl)sulfonyl)-1 ,5-dimethyl-N-((2-methylquinazolin-5- yl)methyl)-1 H-pyrrole-2-carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-4-((4-hydroxypiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-1 H- pyrrole-2-carboxamide;N-((6-fluoroquinoxalin-5-yl)methyl)-4-((4-hydroxypiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-1 H- pyrrole-2-carboxamide;N-(2-(difluoromethyl)-6-methoxybenzyl)-4-((4-hydroxypiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-4-((4-(difluoromethyl)piperidin-1-yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((6-chloroquinoxalin-5-yl)methyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;1 ,5-dimethyl-N-((3-methylcinnolin-5-yl)methyl)-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;N-((1 ,6-naphthyridin-5-yl)methyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;4-((1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-4-((1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)sulfonyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((6-amino-3-fluoropyridin-2-yl)methyl)-4-((1 ,3-dihydro-2H-pyrrolo[3,4c]pyridin-2- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((5-amino-3-fluoropyridin-2-yl)methyl)-4-((1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((1 H-indazol-4-yl)methyl)-4-((1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)sulfonyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;(S)-N-(2-fluoro-6-methoxybenzyl)-1 ,5-dimethyl-4-((3-methyl-5-oxopiperazin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;4-((7,8-dihydropyrido[3,4-d]pyridazin-6(5H)-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((3-methyl-5,6-dihydroimidazo[1 ,5-a]pyrazin-7(8H)-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-4-((5,6-dihydro-[1 ,2,4]triazolo[4,3-a]pyrazin-7(8H)- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((1 ,5,6,7-tetrahydro-4H-pyrazolo[4,3- b]pyridin-4-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((3-oxopiperazin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;4-((3-aminopiperidin-1-yl)sulfonyl)-N-((6-chloroquinolin-5-yl)methyl)-1,5-dimethyl-1H-pyrrole- 2-carboxamide;4-((4H-thieno[3,4-c]pyrrol-5(6H)-yl)sulfonyl)-N-((8-aminoquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-4-((6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-1,5-dimethyl-4-((4-methyl-3,6-dihydropyridin-1(2H)- yl)sulfonyl)-1H-pyrrole-2-carboxamide;4-((5,6-dihydropyrrolo[3,2-c]pyrazol-4(1H)-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;4-((5,6-dihydropyrrolo[3,2-c]pyrazol-4(1H)-yl)sulfonyl)-N-(2-fluoro-6-methoxybenzyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;4-((2,3-dihydro-1 H-pyrido[2,3-b][1 ,4]oxazin-1-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;(R)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((2-methylmorpholino)sulfonyl)-1H- pyrrole-2-carboxamide;(S)-N-((6-fluoroquinolin-5-yl)methyl)-1,5-dimethyl-4-((2-methylmorpholino)sulfonyl)-1H- pyrrole-2-carboxamide;4-(dimethylsulfamoyl)-N-[(6-fluoro-5-quinolyl)methyl]-1 ,5-dimethyl-pyrrole-2-carboxamide;N-[(6-fluoro-5-quinolyl)methyl]-1,5-dimethyl-4-[(3S)-3-methylpiperazin-1-yl]sulfonyl-pyrrole-2- carboxamide;4-(((3R,4S)-3-amino-4-methylpiperidin-1-yl)sulfonyl)-N-(2-fluoro-6-methoxybenzyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-4-(((3r,4r)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-4-(((3S,4S)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-(2-fluoro-6-methoxybenzyl)-4-(((3r,4r)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-(2-fluoro-6-methoxybenzyl)-4-(((3S,4S)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-4-((3,4-dihydro-2,6-naphthyridin-2(1 H)-yl)sulfonyl)-5- methyl-1H-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-4-((6,7-dihydrothieno[3,2-c]pyridin-5(4H)- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;4-((4-chlorophenyl)sulfonyl)-N-((6-fluoroquinoxalin-5-yl)methyl)-1,5-dimethyl-1H-pyrrole-2- carboxamide;4-((4-chlorophenyl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1H-pyrrole-2- carboxamide;1.5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-4-((1,4,6,7-tetrahydro-5H-pyrazolo[4,3- c]pyridin-5-yl)sulfonyl)-1H-pyrrole-2-carboxamide;4-((5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)sulfonyl)-1,5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-1H-pyrrole-2-carboxamide;4-((4,6-dihydropyrrolo[3,4-c]pyrazol-5(1H)-yl)sulfonyl)-1 ,5-dimethyl-N-((2-methylquinazolin-5- yl)methyl)-1 H-pyrrole-2-carboxamide;4-((6,7-dihydro-[1 ,2, 3]triazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-1 ,5-dimethyl-N-((2- methylquinazolin-5-yl)methyl)-1H-pyrrole-2-carboxamide;1.5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-4-((3,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((3,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5- c]pyridin-5-yl)sulfonyl)-1H-pyrrole-2-carboxamide;4-((5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((2-amino-...

Claims

CLAIMS1. A compound according to Formula (I) below, or a pharmaceutically acceptable salt thereof:wherein:LA is a linker group of the formula -[CRL1RL2]m- in which m is an integer selected from 1, 2 or 3, and RL1and RL2are each independently selected from hydrogen or (1 -3C)alkyl;Ri is selected from aryl or heteroaryl, each of which being optionally substituted by one or more RIA substituents, wherein each RIA is independently selected from halo, cyano or a group of the formula:-WA-WB-WC whereinWA is absent or (1-6C)alkylene;WB is absent or selected from -O-, -S-, -N(R1 B)-, -C(O)-, -C(O)O-, -OC(O)-, - C(O)N(R1 B)-, -N(R1 B)C(O)-, -S(O)-, -S(O)2-, -S(O)(=NR1 B)-, -S(O)2N(R1 B)- or N(R1 B)SO2; wherein R1 Bis selected from hydrogen or (1 -3C)alkyl;Wc is selected from hydrogen, (1 -6C)alkyl), (3-6C)cycloalkyl or heterocyclyl; wherein Wc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1-4C)alkyl, NR1cR1 D, OR1c, C(O)R1c, C(O)OR1c, OC(O)R1c, C(O)N(R1 D)R1c, N(R1 D)C(O)R1c, S(O)qR1c(where q is 0, 1 or 2), S(O)(=NR1 D)R1c, S(O)2N(R1 D)R1cor N(R1 D)S(O)2R1c; wherein R1cand R1 Dare each independently selected from hydrogen, (1- 3C)alkyl or (3-6C)cycloalkyl, wherein (1 -3C)alkyl or (3-6C)cycloalkyl are eachoptionally substituted with one or more substituents selected from halo, cyano, hydroxy or NH2;Ring A is:wherein:Xi is selected from NRXIN; wherein RXIN is selected from hydrogen or (1 -3C)alkyl optionally substituted by one or more fluoro substituents;X2 is selected from CRx2 or N; wherein RXIN is selected from hydrogen, methyl or ethyl;R3xis selected from halo, cyano, or a group of the formula-XA-XB-XC wherein:XA is absent or (1-6C)alkylene;XB is absent or selected from -O-, -S-, -N(R3A)-, -C(O)-, -C(O)O-, -OC(O)-, - N(R3A)C(O)-, -S(O)-, -S(O)2-, -S(O)(=NR3A)-, -S(O)2N(R3A)- or N(R3A)SO2; wherein R3A is selected from hydrogen or (1 -3C)alkyl;Xc is selected from hydrogen, (1 -6C)alkyl), (3-6C)cycloalkyl or heterocyclyl; i) wherein Xc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1-4C)alkyl, NR3BR3C, OR3B, C(O)R3B, C(O)OR3B, OC(O)R3B, C(O)N(R3C)R3B, N(R3C)C(O)R3B, S(O)qR3B(where q is 0, 1 or 2), S(O)(=NR3C)R3B, S(O)2N(R3C)R3B or N(R3C)S(O)2RSB; wherein R3B and R3c are each independently selected from hydrogen, (1- 3C)alkyl or (3-6C)cycloalkyl, wherein (1 -3C)alkyl or (3-6C)cycloalkyl are each optionally substituted with one or more substituents selected from halo, cyano, hydroxy or NH2;Z is selected from (1 -4C)alkyl, (3-12C)cycloalkyl, heterocyclyl, aryl, heteroaryl, (3- 7C)cycloalkyl(1-4C)alkyl, heterocyclyl(1-4C)alkyl, aryl(1-4C)alkyl, heteroaryl(1-4C)alkyl or NR6NR7N;wherein any alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, (3-7C)cycloalkyl(1- 4C)alkyl, heterocyclyl(1-4C)alkyl, aryl(1-4C)alkyl or heteroaryl(1-4C)alkyl, is optionally substituted by one or more substituents selected from halo, cyano, oxo, (1 -3C)alkyl, (2- 3C)alkenyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, aryl or heteroaryl, NRSCRSD, =CR6CR6D, OR6C, C(O)R6C, C(O)OR6C, C(O)N(R6D)R6C, N(R6D)C(O)R6C, SR6C, S(O)R6C, S(O)2R6c, S(O)2N(R6D)R6C or N(R6D)S(O)2R6C, (1-3C)alkyl, (1-3C)haloalkoxy); wherein R6c and RSD are each independently selected from hydrogen or (1 -3C)alkyl; wherein any (1 -3C)alkyl, (2-3C)alkenyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, aryl or heteroaryl substituent on group Z, including those in R6c and RSD, may be optionally further substituted by one or more substituents selected from halo, cyano, oxo, (1-3C)alkyl, (1-3C)haloalkyl, NRSERSF, OR6E, C(O)R6E, C(O)OR6E, OC(O)R6E, C(O)N(R6F)R6E, N(R6F)C(O)R6E, S(O)VR6E (where v is 0, 1 or 2), S(O)2N(R6F)R6E or N(R6F)S(O)2R6E; wherein R6E and RSF are each independently selected from hydrogen or (1 -3C)alkyl; wherein R6Nand R7Nare each independently selected from (1 -4C)alkyl or (3- 7C)cycloalkyl, wherein the (1 -4C)alkyl or (3-7C)cycloalkyl in R6Nand R7Nare optionally substituted with one of more substituents selected from halo, cyano, oxo, (1 -3C)alkyl, (2- 3C)alkenyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, aryl or heteroaryl, NRSGRSH, OR6G, C(O)R6G, C(O)OR6G, C(O)N(R6H)R6G, N(R6H)C(O)R6G, SR6G, S(O)R6G, S(O)2R6G, S(O)2N(R6H)R6G or N(R6H)S(O)2R6G; wherein RSH and R6c are each independently selected from hydrogen or (1 -3C)alkyl; i) with the proviso that: if Ri is a phenyl ring, then the phenyl ring comprises at least one substituent other than hydrogen in the ortho position; and ii) the compound is not:1 ,5-dimethyl-N-(2-methylbenzyl)-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;N-(2-methoxybenzyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H- pyrrole-2-carboxamide; orN-(2-chlorobenzyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide.

2. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein LA is a linker group of the formula -[CRL1RL2]m- in which m is an integer selected from 1 or 2, and each occurrence of RL1and RL2are each independently selected from hydrogen or methyl;optionally wherein LA is a linker group of the formula -[CRL1RL2]— , wherein RL1and RL2are independently selected from hydrogen or methyl; further optionally wherein LA is a linker group of the formula -[CH2]-.

3. A compound according to claim 1 or claim 2, or a pharmaceutically acceptable salt thereof, wherein R1 is selected from phenyl, naphthyl or mono or bicyclic heteroaryl, each of which being optionally substituted by one or more substituents RIA, wherein each RIA is independently selected from halo, cyano or a group of the formula:-WA-WB-WC whereinWA is absent or (1-6C)alkylene;WB is absent or selected from -O-, -S-, -N(R1 B)-, -C(O)-, -C(O)O-, -OC(O)-, - C(O)N(R1 B)-, -N(R1 B)C(O)-, -S(O)-, -S(O)2-, -S(O)(=NR1 B)-, -S(O)2N(R1 B)- or N(R1 B)S(O)2; wherein R1cis selected from hydrogen or methyl;Wc is selected from hydrogen, (1-6C)alkyl), (3-6C)cycloalkyl or 4- to 6- membered heterocyclyl; wherein Wc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1-2C)alkyl, NR1cR1 D, OR1c, C(O)R1c, C(O)N(R1 D)R1c, S(O)qR1c(where q is 0, 1 or 2), S(O)(=NR1 D)R1cor S(O)2N(R1 D)R1c; wherein R1cand R1care each independently selected from hydrogen, (1 -2C)alkyl or (3-6C)cycloalkyl, wherein any alkyl or cycloalkyl present in an optional substituent in a Wc group are each optionally substituted with one or more substituents selected from halo, cyano or NH2.

4. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R1 is selected from phenyl, naphthyl or mono or bicyclic heteroaryl, each of which being optionally substituted by one or more substituents RIA, wherein each RIA is independently selected from halo, cyano or a group of the formula:-WA-WB-WC whereinWA is absent or (1-3C)alkylene;WB is absent or selected from -O-, -S-, -N(R1 B)-, -C(O)-, -C(O)O-, - C(O)N(R1 B)-, -N(R1 B)C(O)-, -S(O)-, -S(O)2-, -S(O)(=NR1 B)- or -S(O)2N(R1 B)-; wherein R1cis selected from hydrogen or methyl;Wc is selected from hydrogen or (1 -2C)alkyl);wherein the (1 -2C)alkyl) in the Wc group is optionally further substituted by one or more fluoro substituents; optionally wherein Ri is selected from phenyl, naphthyl or mono or bicyclic heteroaryl, each of which being optionally substituted by one or more substituents RIA, wherein each RIA is independently selected from halo, cyano or a group of the formula:-WA-WB-WC whereinWA is absent or (1-3C)alkylene;WB is absent or selected from -O-, -S-, -N(R1 B)-, -C(O)-, -C(O)O-, - C(O)N(R1c)- or -N(RiB)C(O)-; wherein R1 Bis selected from hydrogen or methyl;Wc is selected from hydrogen or (1 -2C)alkyl); wherein the (1 -2C)alkyl) in the Wc group is optionally further substituted by one or more fluoro substituents; further optionally wherein Ri is selected from phenyl, naphthyl, monocylic heteroaryl or bicyclic heteroaryl, each of which being optionally substituted by one or more substituents RIA, wherein each RIA is independently selected from fluoro, chloro, cyano, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2, OMe or OH.

5. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein Ri is: i) a group with a formula selected from:wherein:R4 is selected from hydrogen, halo (e.g. fluoro, chloro), cyano, (1 -3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe orOH; andRs, Re, R7 and Rs are each independently selected from hydrogen, halo, cyano, (1 -3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; ii) a group with the formula:wherein:R9is selected from hydrogen, halo (e.g. fluoro, chloro), cyano, (1-3C)alkyl, (1- 3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH; andR10, R11 , R12, R13, R14 and R15 are each independently selected from hydrogen, halo, cyano, (1-3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2 or CH2F), (1-3C)haloalkoxy (e.g. OCF3, OCHF2 or OCH2F), NH2, OMe or OH; iv) a group with a formula:wherein:R23, R24, R25, R26, R27 and R28 are each independently selected from hydrogen, halo, cyano, (1 -3C)alkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), (1-3C)haloalkoxy (e.g.OCF3, OCHF2or OCH2F), NH2, OMe or OH;RiN is selected from hydrogen or (1-4C)alkyl; andR2N is selected from hydrogen or (1 -4C)alkyl; or vi) a group with a formula:wherein:R29, R30, R31 and R32 are each independently hydrogen, halo, cyano, (1- 3C)alkyl, (3-6C)cycloalkyl, (1-3C)haloalkyl (e.g. CF3, CHF2or CH2F), CI- 3C)haloalkoxy (e.g. OCF3, OCHF2or OCH2F), NH2, OMe or OH.

6. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein Ri is: i) a group with the formula:wherein:R4is selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g.CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F) or OMe;Rs is selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2or OMe;Re is selected from hydrogen, halo, methyl or NH2;R7 is selected from hydrogen, halo, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2or OMe; andRs is selected from hydrogen, halo (e.g. fluoro, chloro), cyano, methyl, fluoromethyl (e.g. CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F) NH2or OMe;wherein:R4pis selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g.CF3, CHF2 or CH2F), fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F) or OMe; R8Pis selected from hydrogen, fluoromethoxy (e.g. OCF3, OCHF2 or OCH2F), NH2or OMe;RePis selected from hydrogen, or NH2;R7Pis selected from hydrogen, fluoromethoxy (e.g. OCF3, OCHF2or OCH2F), NH2or OMe; andRsp is selected from hydrogen, halo (e.g. fluoro, chloro), methyl, fluoromethyl (e.g. CF3, CHF2or CH2F), fluoromethoxy (e.g. OCF3, OCHF2or OCH2F) or OMe; optionally wherein at least one of R4Pand R8Pis not hydrogen; iii) a group with a formula selected from:wherein:R9is selected from hydrogen, halo (e.g. fluoro, chloro), methyl or fluoromethyl (e.g. CF3, CHF2or CH2F);R10 is selected from hydrogen or NH2;R11 is selected from hydrogen, NH2or OH;RI2is hydrogen;R11 is selected from hydrogen or methyl;R14 is selected from hydrogen or methyl; andR15 is hydrogen.

7. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein Ri is: i) a group with a formula selected from:wherein:R4 is selected from hydrogen, methyl or halo (e.g. fluoro or chloro);Rs is selected from hydrogen or NH2;R7 is hydrogen; andRs is hydrogen or methoxy;wherein:R4pis selected from hydrogen or fluoro; R8Pis hydrogen;RePis hydrogen;R7Pis hydrogen; andRsp is selected from hydrogen or methoxy; wherein at least one of R4Pand R8Pis not hydrogen;iii) a group with a formula selected from:wherein:R9is selected from hydrogen, fluoro or chloro;R10 is hydrogen;R11 is selected from hydrogen or NH2;R12 is hydrogen; R13 is selected from hydrogen or methyl;R14 is hydrogen; andR15 is hydrogen.

8. A compound according to any one of the preceding claims, wherein if R1 isthen at least one of R4Pand R8Pis not hydrogen, preferably both of R4Pand R8Pare not hydrogen.

9. A compound according to any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, wherein: i) Ri is:wherein:R4is selected from hydrogen, methyl or halo (e.g. fluoro or chloro); R5 is selected from hydrogen or NH2; andRs is hydrogen or methoxy; ii) R1 is:wherein R4 is selected from hydrogen or halo; iii) R1 is:wherein R4 is selected from hydrogen, methyl or halo; and R7 is selected from hydrogen or NH2; iv) R1 is:wherein R7 is selected from hydrogen or NH2and Rs is selected from hydrogen or methyl; or v) R1 is selected from:whereinR9is selected from hydrogen, methyl, fluoro or chloro;R11 is selected from hydrogen or NH2;R13 is selected from hydrogen or methyl.

10. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from hydrogen or (1 -3C)alkyl; optionally wherein R2 is selected from hydrogen or methyl; further optionally wherein R2 is hydrogen.

11. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein Ring A is selected from:wherein RXI N is selected from hydrogen, methyl or ethyl, wherein the methyl and ethyl are optionally substituted by one or more fluoro substituents; andRsx is as defined in claim 1; optionally wherein Ring A is:wherein RXI N is selected from hydrogen, methyl or ethyl, wherein the methyl and ethyl are optionally substituted by one or more fluoro substituents; andRsx is as defined in claim 1.

12. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein Rsx is selected from halo, cyano, or a group of the formula:-XA-XB-XC wherein:XA is absent or (1-4C)alkylene;XB is absent or selected from -O-, -S-, -N(RSA)-, -C(O)-, -C(O)O-, -OC(O)- or - N(RSA)C(O)-; wherein RSA is selected from hydrogen or (1 -2C)alkyl;Xc is selected from hydrogen, (1 -6C)alkyl), (3-6C)cycloalkyl or heterocyclyl; wherein Xc is optionally further substituted by one or more substituent groups independently selected from halo, cyano, oxo, (1-4C)alkyl, NRSBRSC, ORSB, C(O)RSB, C(O)ORSB, OC(O)RSB, C(O)N(R3C)R3B; wherein R3B and R3c are each independently selected from hydrogen, (1-3C)alkyl or (3-6C)cycloalkyl, wherein (1 -3C)alkyl or (3- 6C)cycloalkyl are each optionally substituted with one or more substituents selected from halo, cyano, hydroxy or NH2.

13. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein Rsx is selected from halo, cyano, (1-2C)alkyl cyclopropyl, wherein any (1 -2C)alkyl or cyclopropyl in a Rsx group is optionally further substituted by one or more substituents selected from halo or cyano; optionally wherein Rsx is selected from fluoro, chloro, bromo, cyano, methyl or cyclopropyl, wherein methyl or cyclopropyl are optionally substituted by one or more fluoro substituents.

14. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein Z is selected from (1-4C)alkyl, (3-12C)cycloalkyl, heterocyclyl, phenyl, heteroaryl or NR6NR7N, wherein any (1-4C)alkyl, (3-12C)cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally substituted by one or more substituents selected from halo, cyano, oxo, (1- 3C)alkyl, (2-3C)alkenyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, aryl, heteroaryl, NRSCRSD, =CR6CR6D, ORGC, C(O)R6c, C(O)OR6c, C(O)N(R6D)R6C, N(R6D)C(O)R6C, SRGC, S(O)R6c or S(O)2R6c; wherein R6c and RGD are each independently selected from hydrogen or (1-3C)alkyl; wherein any (1 -3C)alkyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, aryl or heteroaryl substituent on group Z, including R6c and RBD, is optionally further substituted by one or more substituents selected from halo, cyano, oxo, (1-3C)alkyl, (1-3C)haloalkyl, NRGERSF, ORGE, C(O)RGE, C(O)ORBE or OC(O)RBE; wherein RGE and RGF are each independently selected from hydrogen or (1 -3C)alkyl; andwherein R6Nand R7Nare each independently selected from hydrogen, (1 -4C)alkyl or (3- 6C)cycloalkyl; wherein R6Nand R7Nare each independently selected from (1 -4C)alkyl or (3- 7C)cycloalkyl, wherein the (1 -4C)alkyl or (3-7C)cycloalkyl in R6Nand R7Nare optionally substituted with one of more substituents selected from halo, cyano, oxo, (1 -3C)alkyl, (2- 3C)alkenyl, (3-6C)cycloalkyl, 4- to 7-membered heterocyclyl, aryl or heteroaryl, NRSGRSH, OR6G, C(O)R6G, C(O)OR6G, C(O)N(R6H)R6G, N(R6H)C(O)R6G, SR6G, S(O)R6G, S(O)2R6G, S(O)2N(R6H)R6G or N(R6H)S(O)2R6G; wherein RGH and R6c are each independently selected from hydrogen or (1 -3C)alkyl.

15. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein Z is selected from (3-8C)cycloalkyl, a 4- to 12-membered nitrogen linked heterocyclic ring (including fused, bridged and spirocyclic heterocyclic rings), phenyl, mono- or bicyclic heteroaryl or NR6NR7N; wherein any (3-8C)cycloalkyl, 4- to 12-membered nitrogen linked heterocyclic ring, phenyl or mono- or bicyclic heteroaryl may be optionally substituted by one or more substituents selected from halo, cyano, oxo, (1-3C)alkyl, (3-4C)cycloalkyl, 5-membered heteroaryl, NRSCRSD, =CR6CR6D, ORGC, C(O)R6c, C(O)OR6c, C(O)N(R6D)R6C, N(R6D)C(O)R6C, SRGC or S(O)2R6c; wherein R6c and RGD are each independently selected from hydrogen or (1- 3C)alkyl; wherein any (1 -3C)alkyl, (3-4C)cycloalkyl or 5-membered heteroaryl present substituent on group Z, including those in R6c and RBD, is optionally further substituted by one or more substituents selected from halo, cyano, oxo, NRGERSF, ORGE, C(O)RGE, C(O)ORBE or OC(O)RBE; wherein RGE and RGF are each independently selected from hydrogen or (1- 3C)alkyl; wherein R6Nand R7Nare each independently selected from (1 -4C)alkyl which is optionally substituted by one or more substituents selected from halo, cyano, oxo, (3- 6C)cycloalkyl, NRGGR6H, ORGG or C(O)RGG; wherein R6c and Ren are each independently selected from hydrogen or (1 -2C)alkyl.

16. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein Z is selected from 5- to 6-membered monocyclic heterocyclyl, a 4- to 10-membered nitrogen-linked bicyclic heterocylic ring fused to an aromatic or heteroaromatic ring, phenyl or NR6NR7N; wherein the 5- to 6-membered monocyclic heterocyclyl or 4- to 10-membered fused bicyclic ring comprising a non-aromatic ring fused to an aromatic ring may be optionally substituted by one or more substituents selected from fluoro, chloro, cyano, oxo, methyl,=CH2, NH2, methoxy, hydroxy(1-2C) alkyl, OH, fluoromethoxy, fluoromethyl (e.g. CF3, CHF2or CH2F) or S-CH3; wherein R6Nis (1 -2C)alkyl and R7Nis (1 -2C)alkyl which is optionally substituted by (3-4C)cycloalkyl.

17. A compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein Z has a structure selected from:wherein any of the group Z rings above may be substituted on an available carbon atom by one or more substituents as defined in any one of the preceding claims; and R6Nand R7Nare as defined in any one of the preceding claims;Rzi, RZ2, RZS, RZ4, RZS, Rze, RZ?, RZS, Rzg, RZ , RZI 1 , Rzi2, Rz and Rzu are selected from hydrogen or (1 -2C)alkyl, preferably hydrogen or methyl; optionally wherein the group Z rings above may be substituted on an available carbon atom by one or more substituents selected from halo, cyano, oxo, (1 -3C)alkyl, =CR6cR6D, (2-3C)alkenyl, (3-6C)cycloalkyl, 5-membered heteroaryl, (1-3C)haloalkyl, N RSCRSD, OR6c, SR6c, S(O)R6c orS(O)2R6c; wherein R6c is selected from hydrogen or (1- 2C)alkyl; wherein any (1 -3C)alkyl substituent on the ring above is optionally further substituted by one or more substituents selected from halo, cyano, oxo, (1 -3C)alkyl, (1-3C)haloalkyl, N RSERSF or ORSE; wherein RSE and Rep are each independently selected from hydrogen or methyl; and R6Nand R7Nare each independently selected from (1 -4C)alkyl which is optionally substituted by (3-4C)cycloalkyl.

18. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, having the structural formula (la):wherein R1, RXIN, RSX and Z are as defined in any one of the preceding claims; optionally wherein: Ri is selected from:wherein:R9is selected from hydrogen, methyl, fluoro or chloro; R11 is selected from hydrogen or NH2;R13 is selected from hydrogen or methyl;RXI N is selected from hydrogen, methyl or ethyl, wherein the methyl and ethyl are optionally substituted by one or more fluoro substituents;R3xis selected from chloro or methyl, wherein methyl is optionally substituted by one or more substituents selected from fluoro, hydroxy or NH2; Z is selected from:wherein:R100, R101, R1c2 and R103 are each selected from hydrogen or methyl;Rzs, RZS, Rzi2, Rz and RZu are selected from hydrogen or a prodrug moiety of the formula:R104 is selected from hydrogen or methyl; and R105 is selected from hydrogen or hydroxy.

19. A compound selected from:4-(3-azabicyclo[3.1 ,0]hexan-3-ylsulfonyl)-1 ,5-dimethyl-N-(5-quinolylmethyl)pyrrole-2- carboxamide;4-[[3-(hydroxymethyl)-1-piperidyl]sulfonyl]-1,5-dimethyl-N-(5-quinolylmethyl)pyrrole-2- carboxamide;4-(azepan-1-ylsulfonyl)-1 ,5-dimethyl-N-(2-methylbenzyl)-1 H-pyrrole-2-carboxamide;4-((3-azabicyclo[4.1 ,0]heptan-3-yl)sulfonyl)-1 ,5-dimethyl-N-(2-methylbenzyl)-1 H-pyrrole-2- carboxamide;4-((3,4-dihydroisoquinolin-2(1 H)-yl)sulfonyl)-1 ,5-dimethyl-N-(2-methylbenzyl)-1 H-pyrrole-2- carboxamide;4-((4-hydroxypiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(2-methylbenzyl)-1 H-pyrrole-2- carboxamide;5-bromo-1-methyl-4-[(4-methyl-1-piperidyl)sulfonyl]-N-(5-quinolylmethyl)pyrrole-2- carboxamide;5-cyano-1-methyl-4-[(4-methyl-1-piperidyl)sulfonyl]-N-(5-quinolylmethyl)pyrrole-2- carboxamide;5-cyclopropyl-1-methyl-4-[(4-methyl-1-piperidyl)sulfonyl]-N-(5-quinolylmethyl)pyrrole-2- carboxamide;1.5-dimethyl-4-[(4-methyl-1-piperidyl)sulfonyl]-N-(4-quinolylmethyl)pyrrole-2-carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(naphthalen-1-ylmethyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-[(4-methyl-1-piperidyl)sulfonyl]-N-(8-quinolylmethyl)pyrrole-2-carboxamide;N-(5-isoquinolylmethyl)-1 ,5-dimethyl-4-[(4-methyl-1-piperidyl)sulfonyl]pyrrole-2-carboxamide;N-(4-isoquinolylmethyl)-1 ,5-dimethyl-4-[(4-methyl-1-piperidyl)sulfonyl]pyrrole-2-carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;N-((1 H-indol-7-yl)methyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-((3-methylpyridin-4-yl)methyl)-1 H-pyrrole-2-carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(2-(trifluoromethoxy)benzyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-((4-methylpyridin-3-yl)methyl)-1 H-pyrrole- 2-carboxamide;1.5-dimethyl-N-((1-methyl-1 H-indol-4-yl)methyl)-4-((4-methylpiperidin-1 -yl)sulfonyl)-1 H- pyrrole-2-carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(quinoxalin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(pyrazolo[1,5-a]pyridin-4-ylmethyl)-1H- pyrrole-2-carboxamide;N-(2-fluoro-6-methoxybenzyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;N-(3-amino-2-chlorobenzyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl) sulfonyl)- 1 H-pyrrole-2- carboxamide;4-[(4-hydroxypiperidin-1-yl)sulfonyl]-1,5-dimethyl-N-[(quinoline-5-yl)methyl]-1H-pyrrole-2- carboxamide;1.5-dimethyl-N-[(quinoline-5-yl)methyl]-4-(1 ,2,3,4-tetrahydroisoquinoline-2-sulfonyl)-1 H- pyrrole-2-carboxamide;1.5-dimethyl-N-[(quinoline-5-yl)methyl]-4-{[4-(trifluoromethyl)piperidin-1-yl]sulfonyl}-1H- pyrrole-2-carboxamide;1.5-dimethyl-4-[(4-methylpiperidin-1-yl)sulfonyl]-N-[(quinolin-6-yl)methyl]-1H-pyrrole-2- carboxamide;4-(2,3-dihydro-1H-indole-1-sulfonyl)-1,5-dimethyl-N-[(quinolin-5-yl)methyl]-1H-pyrrole-2- carboxamide; give 4-[[4-(hydroxymethyl)-1-piperidyl]sulfonyl]-1,5-dimethyl-N-(6-quinolylmethyl)pyrrole-2- carboxamide;4-(3,4-dihydro-1H-2,6-naphthyridin-2-ylsulfonyl)-1,5-dimethyl-N-(5-quinolylmethyl)pyrrole-2- carboxamide;4-(6-azaspiro[3.4]octan-6-ylsulfonyl)-1,5-dimethyl-N-(5-quinolylmethyl)pyrrole-2- carboxamide;4-(3,4-dihydro-1 H-pyrrolo[1 ,2-a]pyrazin-2-ylsulfonyl)-1 ,5-dimethyl-N-(5- quinolylmethyl)pyrrole-2-carboxamide;4-(3,4-dihydro-1H-2,7-naphthyridin-2-ylsulfonyl)-1,5-dimethyl-N-(5-quinolylmethyl)pyrrole-2- carboxamide;1.5-dimethyl-4-(3-methylpyrrolidin-1-yl)sulfonyl-N-(5-quinolylmethyl)pyrrole-2-carboxamide;1.5-dimethyl-4-morpholinosulfonyl-N-(5-quinolylmethyl)pyrrole-2-carboxamide;4-[(4-fluoro-1-piperidyl)sulfonyl]-1,5-dimethyl-N-(5-quinolylmethyl)pyrrole-2-carboxamide;4-(((3S,4S)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)- 1 H-pyrrole-2-carboxamide;4-{[(3R,4R)-4-hydroxy-3-methylpiperidin-1-yl]sulfonyl}-1 ,5-dimethyl-N-[(quinolin-5-yl)methyl]- 1 H-pyrrole-2-carboxamide;4-(((3S,4R)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide4-{[(3R,4S)-4-hydroxy-3-methylpiperidin-1-yl]sulfonyl}-1,5-dimethyl-N-[(quinolin-5-yl)methyl]-1 H-pyrrole-2-carboxamide;4-[(7-hydroxy-3,4-dihydro-1H-isoquinolin-2-yl)sulfonyl]-1 ,5-dimethyl-N-(5- quinolylmethyl)pyrrole-2-carboxamide;1.5-dimethyl-N-(5-quinolylmethyl)-4-(1 ,4,6,7-tetrahydropyrrolo[3,2-c]pyridin-5- ylsulfonyl)pyrrole-2-carboxamide;4-((6,7-dihydroisoxazolo[4,5-b]pyridin-4(5H)-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-((5-fluoroisoindolin-2-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;4-(isoindolin-2-ylsulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1H-pyrrole-2-carboxamide;4-(((3S,4S)-3-fluoro-4-methylpiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1H- pyrrole-2-carboxamide;4-(((3R,4R)-3-fluoro-4-methylpiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1H- pyrrole-2-carboxamide;1.5-dimethyl-4-((4-methyl-3,6-dihydropyridin-1 (2H)-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;1-ethyl-5-methyl-N-(2-methylbenzyl)-4-((4-methylpiperidin-1-yl)sulfonyl)-1H-pyrrole-2- carboxamide;N-((7-aminoquinazolin-5-yl)methyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H- pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-(2-chloro-6-methoxybenzyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;N-(2-methoxy-6-methylbenzyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-((6-methylquinolin-5-yl)methyl)-1H- pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-(benzo[d]thiazol-7-ylmethyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H-pyrrole-2- carboxamide;N-(2-chloro-6-(trifluoromethoxy)benzyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H- pyrrole-2-carboxamide;N-((4-aminonaphthalen-1 -yl)methyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;N-(5-amino-2-chlorobenzyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;4-((4-hydroxypiperidin-1-yl)sulfonyl)-N-(2-methoxy-6-(trifluoromethyl)benzyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-4-((4-hydroxypiperidin-1-yl)sulfonyl)-1,5-dimethyl-1H- pyrrole-2-carboxamide;N-(2-chloro-6-(difluoromethoxy)benzyl)-4-((4-hydroxypiperidin-1-yl)sulfonyl)-1,5-dimethyl-1H- pyrrole-2-carboxamide;5-chloro-1-methyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;(S)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(1-(quinolin-5-yl)ethyl)-1H-pyrrole-2- carboxamide;(R)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-N-(1-(quinolin-5-yl)ethyl)-1 H-pyrrole-2- carboxamide;N-((6-chloroquinolin-5-yl)methyl)-1,5-dimethyl-4-((4-methyl-3-oxopiperazin-1-yl)sulfonyl)-1H- pyrrole-2-carboxamide;N-((8-hydroxyquinolin-5-yl)methyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H- pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole- 2-carboxamide;N-(3-amino-2-methylbenzyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H-pyrrole-2- carboxamide;N-(3-amino-2-methoxybenzyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;1,5-dimethyl-4-((4-methylcyclohexyl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((1,4,6,7-tetrahydro-5H-pyrazolo[4,3- c]pyridin-5-yl)sulfonyl)-1H-pyrrole-2-carboxamide;N-(2-fluoro-6-methoxybenzyl)-1,5-dimethyl-4-((1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-1,5-dimethyl-4-((1,4,6,7-tetrahydro-5H- pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-1 ,5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-1 H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-1.5-dimethyl-1 H-pyrrole-2-carboxamide;4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-N-(2-fluoro-6-methoxybenzyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;4-(6,7-dihydro-4H-pyrazolo[1 ,5-a]pyrazin-5-ylsulfonyl)-N-[(6-fluoroquinoxalin-5-yl)methyl]-1.5-dimethyl-pyrrole-2-carboxamide;N-[(2-amino-3-methyl-4-pyridyl)methyl]-4-(6,7-dihydro-4H-pyrazolo[1 ,5-a]pyrazin-5- ylsulfonyl)-1 ,5-dimethyl-pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-1.5-dimethyl-1 H- pyrrole-2-carboxamide;4-((3,4-dihydro-2,6-naphthyridin-2(1 H)-yl)sulfonyl)-1 ,5-dimethyl-N-((2-methylquinazolin-5- yl)methyl)-1 H-pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-4-((3,4-dihydro-2,6-naphthyridin-2(1 H)-yl)sulfonyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;5-chloro-4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-N-(2-fluoro-6- methoxybenzyl)-1-methyl-1 H-pyrrole-2-carboxamide;5-chloro-4-(6,7-dihydro-4H-pyrazolo[1 ,5-a]pyrazin-5-ylsulfonyl)-N-[(6- fluoro- 5- quinolyl)methyl]-1-methyl-pyrrole-2-carboxamide;5-chloro-N-((6-fluoroquinolin-5-yl)methyl)-4-((4-hydroxypiperidin-1-yl)sulfonyl)-1-methyl-1 H- pyrrole-2-carboxamide;5-chloro-4-(2,3-dihydropyrrolo[3,2-b]pyridin-1-ylsulfonyl)-N-[(6-fluoro-5-quinolyl)methyl]-1- methyl-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-1 ,5-dimethyl-4-(phenylsulfonyl)-1 H-pyrrole-2- carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-4-((4-chlorophenyl)sulfonyl)-1 ,5-dimethyl-1 H- pyrrole-2-carboxamide;4-((3,4-dihydroisoquinolin-2(1 H)-yl)sulfonyl)-N-(imidazo[1 ,2-a]pyridin-5-ylmethyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-4-((3,4-dihydroisoquinolin-2(1 H)-yl)sulfonyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-4-((7-fluoro-3,4-dihydroisoquinolin-2(1 H)- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;4-((3-hydroxy-5,6-dihydro-[1 ,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((TRANS)-3,4-dimethylpyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;4-((5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((3S,4S)-3-fluoro-4-methylpyrrolidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;4-(((3R,4R)-3-fluoro-4-methylpyrrolidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;(R)-1,5-dimethyl-4-((3-methylpiperidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-((3-methylenepyrrolidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1H-pyrrole-2- carboxamide;(R)-4-((3,3-difluoro-4-methylpyrrolidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;(S)-4-((3,3-difluoro-4-methylpyrrolidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1H- pyrrole-2-carboxamide;1.5-dimethyl-4-((3-(methylthio)azetidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;(S)-1,5-dimethyl-4-((3-methylpiperidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1H-pyrrole-2- carboxamide;4-(((3S,4R)-3-fluoro-4-hydroxypiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((3R,4S)-3-fluoro-4-hydroxypiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((1R,5R)-1 -cyano- 3-azabicyclo[3.1.0]hexan-3-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5- ylmethyl)-1H-pyrrole-2-carboxamide;4-(((1S,5S)-1-cyano-3-azabicyclo[3.1.0]hexan-3-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5- ylmethyl)-1H-pyrrole-2-carboxamide;4-((6,7-dihydro-[1,2,3]triazolo[1,5-a]pyrazin-5(4H)-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5- ylmethyl)-1H-pyrrole-2-carboxamide;1.5-dimethyl-4-((2-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;(S)-4-((3-cyclopropylpyrrolidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1H-pyrrole-2-carboxamide(R)-4-((3-cyclopropylpyrrolidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide4-((2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;(R)-1,5-dimethyl-4-((3-(methylsulfonyl)pyrrolidin-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1H- pyrrole-2-carboxamide;1.5-dimethyl-N-(quinolin-5-ylmethyl)-4-((2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5- yl)sulfonyl)-1H-pyrrole-2-carboxamide;(R)-4-((3-(1 H-pyrazol-4-yl)pyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;(S)-4-((3-(1H-pyrazol-4-yl)pyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;4-((3,3-difluoropiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;4-((6-hydroxy-3-azabicyclo[3.1 ,0]hexan-3-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;1.5-dimethyl-4-((3-methyl-2,5-dihydro-1 H-pyrrol-1-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;4-(((3S,4R)-3-methoxy-4-methylpiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide4-(((3R,4S)-3-methoxy-4-methylpiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide(S)-1,5-dimethyl-4-((7-methyl-6,7-dihydropyrazolo[1,5-a]pyrazin-5(4H)-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((2R,4S)-4-hydroxy-2-methylpyrrolidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;(S)-4-((8-hydroxy-5-azaspiro[2.5]octan-5-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;(R)-4-((8-hydroxy-5-azaspiro[2.5]octan-5-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;1.5-dimethyl-4-((3-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;1.5-dimethyl-N-(quinolin-5-ylmethyl)-4-((3-(trifluoromethyl)-2,5-dihydro-1H-pyrrol-1- yl)sulfonyl)-1H-pyrrole-2-carboxamide;4-((7,7-difluoro-3-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-1,5- dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-((6-(hydroxymethyl)-3-azabicyclo[3.1.0]hexan-3-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5- ylmethyl)-1H-pyrrole-2-carboxamide;4-(((3S,4S)-3-fluoro-4-hydroxypiperidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((S)-3-((R)-1-hydroxyethyl)pyrrolidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((S)-3-((S)-1-hydroxyethyl)pyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((R)-3-((S)-1-hydroxyethyl)pyrrolidin-1-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-(((R)-3-((R)-1-hydroxyethyl)pyrrolidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-((2,3-dihydro-1 H-pyrrolo[3,2-b]pyridin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;4-((2,3-dihydro-1 H-pyrrolo[3,2-b]pyridin-1-yl)sulfonyl)-1 ,5-dimethyl-N-((2-methylquinazolin-5- yl)methyl)-1 H-pyrrole-2-carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-4-((4-hydroxypiperidin-1-yl)sulfonyl)-1,5-dimethyl-1 H- pyrrole-2-carboxamide;N-((6-fluoroquinoxalin-5-yl)methyl)-4-((4-hydroxypiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-1 H- pyrrole-2-carboxamide;N-(2-(difluoromethyl)-6-methoxybenzyl)-4-((4-hydroxypiperidin-1-yl)sulfonyl)-1,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-4-((4-(difluoromethyl)piperidin-1-yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((6-chloroquinoxalin-5-yl)methyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H- pyrrole-2-carboxamide;1 ,5-dimethyl-N-((3-methylcinnolin-5-yl)methyl)-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;N-((1 ,6-naphthyridin-5-yl)methyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;4-((1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-4-((1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((6-amino-3-fluoropyridin-2-yl)methyl)-4-((1,3-dihydro-2H-pyrrolo[3,4c]pyridin-2- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((5-amino-3-fluoropyridin-2-yl)methyl)-4-((1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((1 H-indazol-4-yl)methyl)-4-((1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)sulfonyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;(S)-N-(2-fluoro-6-methoxybenzyl)-1,5-dimethyl-4-((3-methyl-5-oxopiperazin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;4-((7,8-dihydropyrido[3,4-d]pyridazin-6(5H)-yl)sulfonyl)-1,5-dimethyl-N-(quinolin-5-ylmethyl)-1 H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-1,5-dimethyl-4-((3-methyl-5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-4-((5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-1,5-dimethyl-4-((1,5,6,7-tetrahydro-4H-pyrazolo[4,3- b]pyridin-4-yl)sulfonyl)-1H-pyrrole-2-carboxamide;N-((6-chloroquinolin-5-yl)methyl)-1,5-dimethyl-4-((3-oxopiperazin-1-yl)sulfonyl)-1H-pyrrole-2- carboxamide;4-((3-aminopiperidin-1-yl)sulfonyl)-N-((6-chloroquinolin-5-yl)methyl)-1,5-dimethyl-1H-pyrrole- 2-carboxamide;4-((4H-thieno[3,4-c]pyrrol-5(6H)-yl)sulfonyl)-N-((8-aminoquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-4-((6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-1,5-dimethyl-4-((4-methyl-3,6-dihydropyridin-1(2H)- yl)sulfonyl)-1H-pyrrole-2-carboxamide;4-((5,6-dihydropyrrolo[3,2-c]pyrazol-4(1H)-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;4-((5,6-dihydropyrrolo[3,2-c]pyrazol-4(1H)-yl)sulfonyl)-N-(2-fluoro-6-methoxybenzyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;4-((2,3-dihydro-1 H-pyrido[2,3-b][1 ,4]oxazin-1-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;(R)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((2-methylmorpholino)sulfonyl)-1H- pyrrole-2-carboxamide;(S)-N-((6-fluoroquinolin-5-yl)methyl)-1,5-dimethyl-4-((2-methylmorpholino)sulfonyl)-1H- pyrrole-2-carboxamide;4-(dimethylsulfamoyl)-N-[(6-fluoro-5-quinolyl)methyl]-1 ,5-dimethyl-pyrrole-2-carboxamide;N-[(6-fluoro-5-quinolyl)methyl]-1,5-dimethyl-4-[(3S)-3-methylpiperazin-1-yl]sulfonyl-pyrrole-2- carboxamide;4-(((3R,4S)-3-amino-4-methylpiperidin-1-yl)sulfonyl)-N-(2-fluoro-6-methoxybenzyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-4-(((3r,4r)-4-hydroxy-3-methylpiperidin-1 -yl)sulfonyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-4-(((3S,4S)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-(2-fluoro-6-methoxybenzyl)-4-(((3r,4r)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-(2-fluoro-6-methoxybenzyl)-4-(((3S,4S)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-4-((3,4-dihydro-2,6-naphthyridin-2(1 H)-yl)sulfonyl)-5- methyl-1H-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-4-((6,7-dihydrothieno[3,2-c]pyridin-5(4H)- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;4-((4-chlorophenyl)sulfonyl)-N-((6-fluoroquinoxalin-5-yl)methyl)-1,5-dimethyl-1H-pyrrole-2- carboxamide;4-((4-chlorophenyl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1H-pyrrole-2- carboxamide;1.5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-4-((1,4,6,7-tetrahydro-5H-pyrazolo[4,3- c]pyridin-5-yl)sulfonyl)-1H-pyrrole-2-carboxamide;4-((5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)sulfonyl)-1,5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-1H-pyrrole-2-carboxamide;4-((4,6-dihydropyrrolo[3,4-c]pyrazol-5(1H)-yl)sulfonyl)-1 ,5-dimethyl-N-((2-methylquinazolin-5- yl)methyl)-1 H-pyrrole-2-carboxamide;4-((6,7-dihydro-[1 ,2, 3]triazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-1 ,5-dimethyl-N-((2- methylquinazolin-5-yl)methyl)-1H-pyrrole-2-carboxamide;1.5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-4-((3,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((3,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5- c]pyridin-5-yl)sulfonyl)-1H-pyrrole-2-carboxamide;4-((5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((2-amino-3-methylpyridin-4-yl)methyl)-5-chloro-1-methyl-4-((1,4,6,7-tetrahydro-5H- pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-4-(((3S,4R)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;4-((6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-5- methyl-1H-pyrrole-2-carboxamide;4-((2,3-dihydro-1 H-imidazo[1 ,2-b]pyrazol-1-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;4-(((3R,4R)-3-fluoro-4-hydroxypiperidin-1-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;4-((2-oxa-5-azabicyclo[4.1 ,0]heptan-5-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;4-((3-azabicyclo[3.1 ,0]hexan-3-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H- pyrrole-2-carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-4-(pyrrolidin-1-ylsulfonyl)-1 H-pyrrole-2- carboxamide;4-(azetidin-1-ylsulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H-pyrrole-2- carboxamide;4-((1 H-pyrrolo[3,2-b]pyridin-1-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H- pyrrole-2-carboxamide;N-((8-aminoquinolin-5-yl)methyl)-4-((4,6-dihydro-5H-thieno[2,3-c]pyrrol-5-yl)sulfonyl)-1 ,5- dimethyl-1 H-pyrrole-2-carboxamide;N-((8-amino-6-fluoroquinolin-5-yl)methyl)-4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((8-amino-6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((1 ,4,6,7-tetrahydro-5H- pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-((8-amino-6-fluoroquinoxalin-5-yl)methyl)-1 ,5-dimethyl-4-((1 ,4,6,7-tetrahydro-5H- pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;4-((1 H-pyrrol-1-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H-pyrrole-2- carboxamide;4-((3-chloro-1 H-pyrrol-1-yl) sulfonyl)-N-((6-fluoroquinolin-5-yl) methyl)-"! , 5-dimethyl-1 H- pyrrole-2-carboxamide;4-((2-chloro-1 H-pyrrol-1-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H- pyrrole-2-carboxamide;N-((6-fluoroquinolin-5-yl)methyl)-5-methyl-4-((2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5- yl)sulfonyl)-1-(2,2,2-trifluoroethyl)-1 H-pyrrole-2-carboxamide;N-((8-aminoisoquinolin-5-yl)methyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H- pyrrole-2-carboxamide; and4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-N-(2-fluoro-6-methoxybenzyl)-1 ,5- dimethyl-1 H-imidazole-2-carboxamide;N-((6-fluoroquinazolin-5-yl)methyl)-1 ,5-dimethyl-4-((1 ,4,6,7-tetrahydro-5H-pyrazolo[4,3- c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;N-(1 ,3-benzothiazol-4-ylmethyl)-1 ,5-dimethyl-4-(1 ,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5- ylsulfonyl)pyrrole-2-carboxamide;N-(benzo[d]thiazol-7-ylmethyl)-1,5-dimethyl-4-((1 ,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin- 5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;4-(4-chlorophenyl)sulfonyl-1,5-dimethyl-N-[(2-methylquinazolin-5-yl)methyl]pyrrole-2- carboxamide;4-(4-chlorophenyl)sulfonyl-1,5-dimethyl-N-(quinazolin-5-ylmethyl)pyrrole-2-carboxamide; 4-((1 H-indazol-5-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H-pyrrole-2- carboxamide;4-(1 H-indazol-5-ylsulfonyl)-1 ,5-dimethyl-N-[(2-methylquinazolin-5-yl)methyl]pyrrole-2- carboxamide;4-(1 H-indazol-5-ylsulfonyl)-1 ,5-dimethyl-N-(quinazolin-5-ylmethyl)pyrrole-2-carboxamide; N-((1 ,6-naphthyridin-5-yl)methyl)-4-((1 H-indazol-5-yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2- carboxamide;4-((1 H-indazol-5-yl)sulfonyl)-N-((6-chloro-2-methylquinazolin-5-yl)methyl)-1 ,5-dimethyl-1 H- pyrrole-2-carboxamide;N-((1-aminoisoquinolin-4-yl)methyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H- pyrrole-2-carboxamide;1 ,5-dimethyl-4-((7-methyl-1 H-indazol-5-yl)sulfonyl)-N-(quinazolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;N-((1 ,6-naphthyridin-5-yl)methyl)-1 ,5-dimethyl-4-((7-methyl-1 H-indazol-5-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;N-((1 ,7-naphthyridin-5-yl)methyl)-1 ,5-dimethyl-4-((7-methyl-1 H-indazol-5-yl)sulfonyl)-1 H- pyrrole-2-carboxamide;4-(1 H-indazol-5-ylsulfonyl)-1 ,5-dimethyl-N-[(2-methylquinazolin-5-yl)methyl]pyrrole-2- carboxamide;4-((1,3-dihydroisobenzofuran-5-yl)sulfonyl)-1 ,5-dimethyl-N-((2-methylpyrido[4,3-d]pyrimidin-5-yl)methyl)-1H-pyrrole-2-carboxamide;N-((1 ,6-naphthyridin-5-yl)methyl)-4-((1 ,3-dihydroisobenzofuran-5-yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;4-(1,3-dihydroisobenzofuran-5-ylsulfonyl)-1,5-dimethyl-N-[(2-methylquinazolin-5- yl)methyl]pyrrole-2-carboxamide;4-((1 ,3-dihydroisobenzofuran-5-yl)sulfonyl)-1 ,5-dimethyl-N-(quinazolin-5-ylmethyl)-1 H- pyrrole-2-carboxamide;4-((1 ,3-dihydroisobenzofuran-5-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H- pyrrole-2-carboxamide;4-((1 H-indol-5-yl)sulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H-pyrrole-2- carboxamide;N-((1 ,6-naphthyridin-5-yl)methyl)-4-((1 ,3-dihydroisobenzofuran-5-yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;4-((1 H-indol-5-yl)sulfonyl)-N-((6-fluoroimidazo[1 ,2-a]pyridin-5-yl)methyl)-1 ,5-dimethyl-1 H- pyrrole-2-carboxamide;4-((1 H-indol-5-yl)sulfonyl)-N-(imidazo[1 ,2-a]pyridin-5-ylmethyl)-1 ,5-dimethyl-1 H-pyrrole-2- carboxamide;4-(1 H-indol-5-ylsulfonyl)-1 ,5-dimethyl-N-[(2-methylquinazolin-5-yl)methyl]pyrrole-2- carboxamide;4-(1 H-indol-5-ylsulfonyl)-1 ,5-dimethyl-N-(1 ,6-naphthyridin-5-ylmethyl)pyrrole-2-carboxamide;N-((6-fluoroimidazo[1 ,2-a]pyridin-5-yl)methyl)-1 ,5-dimethyl-4-((7-methyl-1 ,4,6,7-tetrahydro- 5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;(S)-1 ,5-dimethyl-4-((7-methyl-1 ,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N- ((2-methylquinazolin-5-yl)methyl)-1 H-pyrrole-2-carboxamide;(R)-1,5-dimethyl-4-((7-methyl-1 ,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N-((2-methylquinazolin-5-yl)methyl)-1 H-pyrrole-2-carboxamide;(S)-1 ,5-dimethyl-4-((7-methyl-1 ,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N-((2-methylquinazolin-5-yl)methyl)-1 H-pyrrole-2-carboxamide;(R)-1 ,5-dimethyl-4-((7-methyl-1 ,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N- ((2-methylquinazolin-5-yl)methyl)-1 H-pyrrole-2-carboxamide;1.5-dimethyl-4-[(7-methyl-1 ,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)sulfonyl]-N-(1 ,6- naphthyridin-5-ylmethyl)pyrrole-2-carboxamide;1.5-dimethyl-N-(quinazolin-5-ylmethyl)-4-((1 ,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridin-5- yl)sulfonyl)-1 H-pyrrole-2-carboxamide;1.5-dimethyl-4-(pyrazolo[1 ,5-a]pyridin-5-ylsulfonyl)-N-(quinazolin-5-ylmethyl)-1 H-pyrrole-2- carboxamide;1.5-dimethyl-4-((6-methyl-1 H-indazol-5-yl)sulfonyl)-N-((2-methylquinazolin-5-yl)methyl)-1 H- pyrrole-2-carboxamide;1.5-dimethyl-4-((4-methyl-1 H-indazol-5-yl)sulfonyl)-N-((2-methylquinazolin-5-yl)methyl)-1 H- pyrrole-2-carboxamide;4-((7-chloro-1 H-indazol-5-yl)sulfonyl)-1 ,5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-1 H- pyrrole-2-carboxamide;4-((7-fluoro-1 H-indazol-5-yl)sulfonyl)-1 ,5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-1 H- pyrrole-2-carboxamide;4-((7-methoxy-1H-indazol-5-yl)sulfonyl)-1,5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-1 H- pyrrole-2-carboxamide;N-((4-chloro-2-methoxypyridin-3-yl)methyl)-4-((5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;4-((5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)sulfonyl)-N-((4-fluoro-2-methoxypyridin-3- yl)methyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;4-((5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)sulfonyl)-N-(2-fluoro-6-methoxybenzyl)-1,5- dimethyl-1 H-pyrrole-2-carboxamide;4-((5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)sulfonyl)-N-((6-fluoroquinazolin-5-yl)methyl)-1.5-dimethyl-1 H-pyrrole-2-carboxamide;4-(6,7-dihydro-4H-pyrazolo[1 ,5-a]pyrazin-5-ylsulfonyl)-N-(imidazo[1,5-a]pyrimidin-6- ylmethyl)-1,5-dimethyl-pyrrole-2-carboxamide;4-((6,7-dihydropyrazolo[1 ,5-a]pyrazin-5(4H)-yl)sulfonyl)-1 ,5-dimethyl-N-(quinazolin-5- ylmethyl)-1H-pyrrole-2-carboxamide;(S)-1,5-dimethyl-4-((7-methyl-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N- (quinazolin-5-ylmethyl)-1H-pyrrole-2-carboxamide;(R)-1,5-dimethyl-4-((7-methyl-1 ,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N- (quinazolin-5-ylmethyl)-1H-pyrrole-2-carboxamide;(S) -1 ,5-dimethyl-4-((7-methyl-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N- (quinazolin-5-ylmethyl)-1H-pyrrole-2-carboxamide;(R)-1,5-dimethyl-4-((7-methyl-1 ,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)sulfonyl)-N- (quinazolin-5-ylmethyl)-1H-pyrrole-2-carboxamide;1.5-dimethyl-4-((5-methyl-5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)sulfonyl)-N-(quinazolin-5-ylmethyl)-1H-pyrrole-2-carboxamide;4-(((3S,4R)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-((2-methylquinazolin-5-yl)methyl)-1H-pyrrole-2-carboxamide;4-(((3S,4R)-4-hydroxy-3-methylpiperidin-1-yl)sulfonyl)-1 ,5-dimethyl-N-(quinazolin-5- ylmethyl)-1H-pyrrole-2-carboxamide;N-((4-chloro-2-methoxypyridin-3-yl)methyl)-4-(((3S,4R)-4-hydroxy-3-methylpiperidin-1- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;N-((4-fluoro-2-methoxypyridin-3-yl)methyl)-4-(((3R,4R)-4-hydroxy-3-methylpiperidin-1- yl)sulfonyl)-1 ,5-dimethyl-1 H-pyrrole-2-carboxamide;4-(N-(cyclopropylmethyl)-N-methylsulfamoyl)-N-((6-fluoroquinolin-5-yl)methyl)-1,5-dimethyl-1 H-pyrrole-2-carboxamide;N-[(6-fluoro-5-quinolyl)methyl]-1,5-dimethyl-4-(4-oxa-7-azaspiro[2.5]octan-7- ylsulfonyl)pyrrole-2-carboxamide;5-chloro-1-methyl-N-[(2-methylquinazolin-5-yl)methyl]-4-(1,4,6,7-tetrahydropyrazolo[4,3- c]pyridin-5-ylsulfonyl)pyrrole-2-carboxamide;4-((1H-indazol-5-yl) sulfonyl)-5-chloro-N-((6-chloro-2-methylquinazolin-5-yl)methyl)-1-methyl-1 H-pyrrole-2-carboxamide;N-((1,6-naphthyridin-5-yl)methyl)-5-chloro-1-methyl-4-((7-methyl-1H-indazol-5-yl)sulfonyl)-1 H-pyrrole-2-carboxamide;4-((1H-indazol-5-yl)sulfonyl)-5-chloro-1-methyl-N-((2-methylquinazolin-5-yl)methyl)-1 H- pyrrole-2-carboxamide;5-(aminomethyl)-4-((6,7-dihydro-1 H-pyrazolo[4,3-c]pyridin-5(4H)-yl)sulfonyl)-1-methyl-N-((2- methylquinazolin-5-yl)methyl)-1H-pyrrole-2-carboxamide;5-(hydroxymethyl)-1-methyl-N-[(2-methylquinazolin-5-yl)methyl]-4-(1, 4,6,7- tetrahydropyrazolo[4,3-c]pyridin-5-ylsulfonyl)pyrrole-2-carboxamide;4-((6,7-dihydro-1 H-pyrazolo[4,3-c]pyridin-5(4H)-yl)sulfonyl)-5-(fluoromethyl)-1-methyl-N-((2- methylquinazolin-5-yl)methyl)-1H-pyrrole-2-carboxamide;5-(difluoromethyl)-4-((6,7-dihydro-1 H-pyrazolo[4,3-c]pyridin-5(4H)-yl)sulfonyl)-1-methyl-N- ((2-methylquinazolin-5-yl)methyl)-1 H-pyrrole-2-carboxamide;4-([1 ,2, 3]triazolo[1 ,5-a]pyridin-5-ylsulfonyl)-N-((6-fluoroquinolin-5-yl)methyl)-1 ,5-dimethyl-1 H- pyrrole-2-carboxamide; and(5-((2-chloro- 5-(((6-chloro-2-methylquinazolin-5-yl)methyl) carbamoyl)- 1 -methyl- 1H-pyrrol-3- yl)sulfonyl)-1H-indazol-1-yl)methyl dihydrogen phosphate; or a pharmaceutically acceptable salt thereof.

20. A pharmaceutical composition comprising a compound according to any one of claims 1 to 19, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

21. A compound according to any one of claims 1 to 19, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 20, wherein provisos i) and ii) in claim 1 do not apply, or a compound selected from:1,5-dimethyl-N-(2-methylbenzyl)-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide;N-(2-methoxybenzyl)-1,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1H-pyrrole-2- carboxamide;N-(2-chlorobenzyl)-1 ,5-dimethyl-4-((4-methylpiperidin-1-yl)sulfonyl)-1 H-pyrrole-2- carboxamide; or a pharmaceutically acceptable salt thereof; for use in: a. therapy; b. the inhibition of activity of an enzyme which binds guanosine monophosphate, guanosine diphosphate, guanosine triphosphate or 5’ guanosine triphosphate capped RNA; c. the inhibition of activity of an enzyme comprising an RNA cap Guanine N-7 methyl transferase; d. the inhibition of NSP14 activity; e. the treatment of a disease or disorder in which the activity of an enzyme which binds guanosine monophosphate, guanosine diphosphate, guanosine triphosphate or 5’ guanosine triphosphate capped RNA is implicated; f. the treatment of a disease or disorder in which RNA cap Guanine N-7 methyl transferase activity is implicated; g. the treatment of a disease or disorder in which NSP14 enzyme activity is implicated; h. the treatment of a viral infection; i. the treatment of a viral infection caused by a virus comprising an enzyme which binds guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5’ guanosine triphosphate (GTP) capped RNA, for example a RNA cap Guanine N-7 methyl transferase, such as NSP14;j. the treatment of a viral infection caused by a virus comprising a RNA cap Guanine N-7 methyl transferase; k. the treatment of a viral infection caused by a virus comprising NSP14; l. the treatment of a viral infection caused by a virus selected from: i. SARS-CoV-2 (causing COVID-19), ii. SARS-CoV (causing severe acute respiratory syndrome (SARS)), iii. SARS-Cov-1 related coronavirus (e.g. SHC014-CoV, WIV1) iv. MERS-CoV (causing Middle East respiratory syndrome), v. HCov-OC43 (causing, inter alia, common cold, pneumonia and bronchiolitis), vi. HCov-229E (causing, inter alia, common cold, pneumonia and bronchiolitis), vii. HCov-HKU (causing, inter alia, common cold, pneumonia and bronchiolitis) viii. HCov-NL63 (causing, inter alia, common cold, pneumonia and bronchiolitis), ix. TGEV (causing transmissible gastroenteritis virus), x. IBV (causing avian infectious bronchitis virus); xi. Bovine coronavirus; xii. Porcine Deltacoronavirus (PDCoV-HKU15) xiii. feline coronavirus (causing Feline infectious peritonitis); xiv. Canine coronavirus; xv. Murine Coronavirus (MHV); xvi. Porcine Epidemic Diarrhea Virus (PEDV); xvii. Pangolin origin Coronaviruses (e.g. pCov-GD01); xviii. Noroviruses (e.g. Norwalk virus [NV] causing gastroenteritis); xix. human rhinovirus (HRV); xx. enterovirus 71 (EV71); xxi. poliovirus (PV); xxii. foot-and-mouth disease virus (FMDV); xxiii. hepatitis A virus (HAV); xxiv. hepatitis E virus (HEV); xxv. porcine teschovirus (PTV); xxvi. Pneumoviridae (e.g. Respiratory Syncytial Virus and Human Metapneumovirus); xxvii. Paramyxoviridae (e.g. Human Parainfluenza Virus, Measles and Henipaviruses including Nipah);xxviii. Flaviviridae (e.g. Dengue Virus DENV1-4, West Nile fever virus, Yellow ever virus, Zika virus, Japanese encephalitis virus, tick borne encephalitis virus, llsutu virus, Powassan virus); xxix. Togaviridae alphavirus (e.g. Chikungunya virus, Venezuelan equine encephalitis virus, Eastern equine encephalitis virus, Mayaro virus, Sindbis virus, O’nyong’nyong virus, Ross River virus, Una virus, Western equine encephalitis virus); xxx. Matonaviridae (e.g. Rubella virus); xxxi. Phenuiviridae (e.g. Rift Valley Fever virus); xxxii. Arenaviridae mammarenavirus (Lassa virus); xxxiii. Rhabdoviridae (e.g. Rabies); xxxiv. Filoviridae (e.g. Ebola virus, Marburg virus, Bundibugyo virus, Sudan virus, Tai Forest ebola virus); xxxv. Orthopoxvirus (e.g. Monkey Pox or Small Pox); xxxvi. Paramyxoviridae henipaviruses (e.g. Nipah, Mojiang, Ghanaian bat henipavirus, Hendra, Langya, Kumasi, Newcastle, Mumps and Madagascar); xxxvii. Paramyxoviridae morbillivirus (e.g. measles); or xxxviii. Nairoviridae othonairovirus (e.g. Crimean-congo hemorrhagic fever virus); p. the treatment of a viral infection caused by a virus of the Coronaviridae family, e.g. SARS-CoV-2, SARS-CoV, MERS-CoV, HCov-OC43, HCov-229E, HCov- HKU and HCov-NL63, Avian Infectious Bronchitis virus (IBV), Bovine coronavirus, feline coronavirus, Murine Coronavirus (MHV) and the Porcine Epidemic Diarrhea Virus; q. the treatment of COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS) r. the treatment of COVID-19. s. inhibiting viral replication of a virus comprising an enzyme which binds guanosine monophosphate (GMP), guanosine diphosphate (GDP), guanosine triphosphate (GTP) or 5’ guanosine triphosphate (GTP) capped RNA; t. inhibiting viral replication of a virus comprising a N7-Guanosine methyl transferase, u. inhibiting viral replication of a virus comprising the NSP14 enzyme; v. inhibiting SARS-CoV-2 viral replication; or w. the production of a NSP14 inhibitory effect; optionally for use use in the treatment of a coronavirus infection, such as COVID-19.

22. The compound or pharmaceutical composition for the use according to claim 21, wherein the compound or pharmaceutical composition are administered in combination with one or more additional therapeutic agents; optionally wherein the one or more additional therapeutic agents are selected from: i. CYP inhibitors such as Ritonavir ii. 3CL protease inhibitors such as Nirmatrelvir, Simnotrelvir, Ensitrelvir, Ibuzatrelvir, CMX990, Simnotrelvir, EDP-235, Pomotrelvir, Olgotrelvir and / or ALG097558; iii. protease inhibitors such as Paxlovid and / or Xiannuoxin; iv. PL protease inhibitors such as Plpro-001 ; v. antivirals such as remdesivir, deuremidevir, galidesivir, favilavir, avifavir, molnupiravir (MK-4482 / EIDD 2801), derivatives of N(4)-hydroxycytidine, AT-527, AT-301 , BLD- 2660, favipiravir, camostat, SLV213, emtrictabine, tenofivir, clevudine, dalcetrapib, boceprevir and / or ABX464; vi. glucocorticoids such as dexamethasone and hydrocortisone; vii. convalescent plasma; viii. a recombinant human plasma such as gelsolin (Rhu-p65N); ix. monoclonal antibodies such as regdanvimab (Regkirova), ravulizumab (Ultomiris), VIR-7831A, R-7832, BRIM 96, BRII-198, COVI- AMG, COVI DROPS (STI-2020), bamlanivimab (LY-CoV555), mavrilimab, leronlimab (PRO140), AZD7442, lenzilumab, infliximab, adalimumab, JS 016, STI-1499 (COVIGUARD), lanadelumab (Takhzyro), canakinumab (Haris), gimsilumab and / or otilimab; x. antibody cocktails such as casirivimab / imdevimab (REGN-Cov2); xi. recombinant fusion protein such as MK-7110 (CD24Fc / SACCOVID); xii. anticoagulants such as heparin and apixaban; xiii. IL-6 receptor agonists such as tocilizumab (Actemra) or sarilumab (Kevzara); xiv. PlKfyve inhibitors such as apilimod dimesylate; xv. RIPK1 inhibitors such as DNL758, DC402234; xvi. VIP receptor agonists such as PB1046; xvii. SGLT2 inhibitors such as dapaglifozin; xviii. TYK inhibitors such as abivertinib; xix. kinase inhibitors such as bemcentinib, acalabrutinib, losmapimod, baricitinib and / or tofacitinib; xx. MEK inhibitors such as ATR-002, PD-0184264, CI-1040, GSK-1120212, GDC-0973, Binimetinib, Selumetinib, PLX-4032, AZD6244, AZD8330, AS-703026, RDEA-119,RO-5126766, RO4987655, PD-0325901, TAK-733, AS703026, PD98059 and PD184352; xxi. H2 blockers such as famotidine; xxii. anthelmintics such as niclosamide, xxiii. furin inhibitors such as diminazene; xxiv. Quercetin and / or Dasatinib; xxv. complement C5a inhibitors; xxvi. modulators of NSP10 / NSP14, NSP9, NSP10, NSP13 and / or NSP15; xxvii. mPro inhibitors such as Nirmatrelvir, Simnotrelvir and Ensetrelvir; or xxviii. modulators of METTL3-METTL14, ALKBH5, FTO, YTHDF1 , YTHDF2, Fibrillarin, NSun2 and / or ADAR1 ; further optionally wherein the one or more additional therapeutic agents is selected from Ritonavir, Molnupiravir and Paxlovid.

23. A method of inhibiting viral replication of a virus comprising an enzyme which binds guanosine monophosphate, guanosine diphosphate, guanosine triphosphate or 5’ guanosine triphosphate capped RNA in vitro or in vivo, said method comprising contacting a cell with therapeutically effective amount of a compound according to any one of claims 1 to 19, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 20; wherein proviso i) and ii) in claim 1 do not apply; optionally wherein the enzyme comprises a RNA cap Guanine N-7 methyl transferase; further optionally wherein the enzyme is NSP14.

24. A method of inhibiting viral replication of a virus, said method comprising contacting a viral RNA cap Guanine N-7 methyl transferase enzyme with a therapeutically effective amount of a viral RNA cap Guanine N-7 methyl transferase inhibitor; optionally wherein the virus is selected from: i. SARS-CoV-2 (causing COVID-19), ii. SARS-CoV (causing severe acute respiratory syndrome (SARS)), iii. SARS-Cov-1 related coronavirus (e.g. SHC014-CoV, WIV1) iv. MERS-CoV (causing Middle East respiratory syndrome), v. HCov-OC43 (causing, inter alia, common cold, pneumonia and bronchiolitis),vi. HCov-229E (causing, inter alia, common cold, pneumonia and bronchiolitis), vii. HCov-HKU (causing, inter alia, common cold, pneumonia and bronchiolitis) viii. HCov-NL63 (causing, inter alia, common cold, pneumonia and bronchiolitis), ix. TGEV (causing transmissible gastroenteritis virus), x. IBV (causing avian infectious bronchitis virus); xi. Bovine coronavirus; xii. Porcine Deltacoronavirus (PDCoV-HKU15) xiii. feline coronavirus (causing Feline infectious peritonitis); xiv. Canine coronavirus; xv. Murine Coronavirus (MHV); xvi. Porcine Epidemic Diarrhea Virus (PEDV); xvii. Pangolin origin Coronaviruses (e.g. pCov-GD01); xviii. Noroviruses (e.g. Norwalk virus [NV] causing gastroenteritis); xix. human rhinovirus (HRV); xx. enterovirus 71 (EV71); xxi. poliovirus (PV); xxii. foot-and-mouth disease virus (FMDV); xxiii. hepatitis A virus (HAV); xxiv. porcine teschovirus (PTV); xxv. Pneumoviridae (e.g. Respiratory Syncytial Virus and Human Metapneumovirus); xxvi. Paramyxoviridae (e.g. Human Parainfluenza Virus, Measles and Henipaviruses including Nipah); xxvii. Flaviviridae (e.g. Dengue Virus DENV1-4, West Nile fever virus, Yellow ever virus, Zika virus, Japanese encephalitis virus, tick borne encephalitis virus, llsutu virus, Powassan virus); xxviii. Togaviridae alphavirus (e.g. Chikungunya virus, Venezuelan equine encephalitis virus, Eastern equine encephalitis virus, Mayaro virus, Sindbis virus, O’nyong’nyong virus, Ross River virus, Una virus, Western equine encephalitis virus); xxix. Matonaviridae (e.g. Rubella virus); xxx. Phenuiviridae (e.g. Rift Valley Fever virus); xxxi. Arenaviridae mammarenavirus (Lassa virus); xxxii. Rhabdoviridae (e.g. Rabies);xxxiii. Filoviridae (e.g. Ebola virus, Marburg virus, Bundibugyo virus, Sudan virus, Tai Forest ebola virus); xxxiv. Orthopoxvirus (e.g. Monkey Pox or Small Pox); xxxv. Paramyxoviridae henipaviruses (e.g. Nipah, Mojiang, Ghanaian bat henipavirus, Hendra, Langya, Kumas, Newcastle, Mumps and Madagascar); xxxvi. Paramyxoviridae morbillivirus (e.g. measles); or xxxvii. Nairoviridae othonairovirus (e.g. Crimean-congo hemorrhagic fever virus); preferably wherein virus is selected from a virus of the Coronaviridae family; more preferably SARS-CoV-2; and / or the RNA cap Guanine N-7 methyl transferase inhibitor inhibitor is a compound according to any one of claims 1 to 20, wherein proviso i) and ii) in claim 1 do not apply.

25. A method of inhibiting method of inhibiting NSP14 activity in vitro or in vivo, said method comprising contacting a cell with a therapeutically effective amount of a compound according to any one of claims 1 to 19, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 20; wherein proviso i) and ii) in claim 1 do not apply.

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