PARP1 inhibitor compounds

Abstract

Dihydroisoquinol in o ne P ARP 1 inhibitors A compound of formula (I) where XD is C, O or N with the proviso that no more than one XD is O and when XD is not C, ring D is non-aromatic, y is 0, 1 or 2,

Description

Technical Field The present invention relates to PARP1 inhibitor compounds, and in particular to PARP1 inhibitor compounds for use in medicine. The inhibitors of the invention may be used in pharmaceutical compositions, and in particular pharmaceutical compositions for treating a cancer. The invention also relates to methods of manufacture of such inhibitors, and methods of treatment using such inhibitors. Background The family of poly(ADP-ribose) polymerases (PARPs) consists of 17 PARP proteins that catalyse the transfer of ADP-ribose to target proteins, a posttranslational process termed PARylation. Target protein modification by PARylation causes significant changes to function and as such PARPs play an important role in many cellular processes such as chromatin remodelling, transcription, replication, recombination, cell cycle progression and DNA damage repair (Kamaletdinova, T. et al. Cell. 2019; 8: 1625). PARP1 and 2 are the most widely studied PARP enzymes, primarily due to their role in DNA damage repair, in particular in the base excision repair (BER) process of DNA single-strand breaks (Ngoi, YL. et al. Cancer J. 2021; 27: 521-528). PARP1 is activated by DNA damage breaks, and the subsequent PARylation of target proteins leads to recruitment of additional factors that initiate repair of DNA lesions. Auto-PARylation of PARP triggers the release of bound PARP from the DNA allowing other DNA repair proteins access to complete lesion repair. This highlights the critical role PARP plays in enabling a cancer cell to repair DNA damage caused by exogenous agents such as radiation therapy and chemotherapeutic agents. Inhibition of PARP enzymes has been utilised as a strategy to selectively kill cancer cells that harbour genetic defects in complementary DNA damage repair pathways (Farmer, H. et al. Nature. 2005; 434: 917-921). This synthetic lethality approach has been demonstrated successfully in tumours with epigenetic modifications or deleterious mutations in BRCA1 and BRCA2, two functionally redundant tumour suppressor proteins involved in DNA doublestrand break (DSB) repair by homologous recombination (HR) (Lord, CJ. and Ashworth, A. Science. 2017; 355: 1152-1158). Such tumours with HR deficiency (HRD) are dependent on PARP function for survival - following PARP inhibition in these tumours, DSB breaks will be processed by alternative error-prone repair pathways leading to genomic instability and cancer cell death. The inhibition of PARP can trap the inactivated PARP at the sites of DNA damage. This leads to replication fork stalling and subsequent collapse in S-phase when the fork reaches the site of the trapped PARP, resulting in the generation of genotoxic DNA double-strand breaks. It is believed that this PARP1-DNA trapping can lead to the selective death of cancer cells harbouring HRD (Farmer, H. et al. Nature. 2005; 434: 917-921). This strategy has led to the successful approval of several PARP inhibitors for the treatment of cancers with HRD, such as in BRCAl / 2-mutated breast, ovarian and prostate cancer, as well as in ovarian and prostate cancer harbouring genomic consequences of HRD, and ovarian cancer in the maintenance setting where platinum sensitivity acts as a surrogate for HRD (Fong, PC. et al. N. Engl. J. Med. 2009; 361:123-134). It has recently been shown that genomic instability, in the form of unrepaired DNA doublestrand breaks or micronuclei disruption can trigger innate immune system activation via the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS), leading to generation of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) and induction of dimerization of stimulator of interferon genes (STING). STING subsequently translocates from the endoplasmic reticulum to the Golgi where it recruits and activates TANK-binding kinase 1 (TBK1). TBK1 phosphorylates interferon regulatory transcription factor 3 (IRF3) which drives the production of type I interferons and supports the induction of an adaptive immune response (Zhu, Y. etal. Mol. Cancer. 2019,18:152). For example, PARP inhibitor-induced STING pathway activation and anti-tumour immune responses have been demonstrated in multiple tumour models, providing rationale for exploiting combinations of PARP inhibitors with immunotherapies for improved therapeutic efficacy (Sen, T. et al. Cancer Discov. 2019; 9: 646-661). For example, the PARP inhibitor Olaparib was also recently shown to induce synthetic lethal effects in combination with a synthetic cyclic dinucleotide STING agonist in DNA damage repair deficient cancer cells and a BRCA-deficient breast cancer model (Pantelidou, C. et al. 2021: bioRxiv 2021.01.26.428337vl). Overall, modulation of nucleic acid sensing pathways via multiple mechanisms has been shown to promote anti-tumour efficacy in a variety of cell and animal models thus demonstrating therapeutic potential for augmenting efficacy of immunotherapies and overcoming resistance to immune checkpoint blockade through use of PARP inhibitors. There are numerous clinical trials ongoing combining PARP inhibitors with immunotherapies (reviewed in Chabanon, RM, et al. Nat. Rev. Cancer. 2021; 21: 701-717). Recently, PARP1 has also been shown to bind the Epstein Barr Virus (EBV) genome and that PARP1 inhibition can alter EBV chromatin structure and latent gene expression (Morgan, SM. et al. Nat. Commun. 2022; 13:187). Hence, PARP1 inhibitors may play a role in cancers where EBV plays a contributing role such as Burkitt's lymphoma, Hodgkin's lymphoma, nasopharyngeal and gastrointestinal cancers. Interestingly, EBV has also been shown to be a causative factor in multiple sclerosis (MS) whereby EBV infection greatly increases the risk of subsequent MS (Bjornevik, K. et al. Science (2021); 375: 296-301). First-generation PARP inhibitors generally demonstrate non-selective activity at PARP1 and 2. Haematological toxicities such as anaemia, neutropenia and thrombocytopenia are associated with clinical use of these molecules which restricts their use in combination with cytotoxic chemotherapies and other targeted agents due to dose-limiting cytopenias (LaFargue, CJ. et al. Lancet Oncol. 2019, 20, el5-e28). Evidence from pre-clinical mouse studies strongly suggests that PARP2 inhibition is a major driver of these haematological toxicities, with PARP2 being particularly linked to erythrogenesis in mice (Farres, J. et al. Blood. 2013; 122: 44-54). In addition, PARP2 function has been shown to be dispensable for anti-tumour activity in HRD mouse cancer models (Ronson, G E. etal. Nat. Commun. 2018, 9: 746). Taken together, these data suggest an unmet medical need for the development of inhibitors with improved selectivity for PARP1 over PARP2 and other PARPs, thus providing expanded therapeutic utility (1) as single agents and (2) in combination with other anti-cancer agents. To date, two PARPl-selective inhibitors, AZD5305 and AZD9574, have entered clinical development. AZD5305 was described as a potent PARP1 inhibitor and trapper with 500-fold selectivity over PARP2 and less off-target activity against secondary pharmacology targets than first-generation PARP inhibitors (Johannes, JW. et al. J. Med. Chern. 2021; 64: 14498-14512). Importantly, significantly less haematotoxicity was observed for AZD5305 in rodent models than with first-generation PARP inhibitors, confirming the reported pathogenic role of PARP2 in haematologic toxicity (111uzzi, G. et al. Clin. Cancer Res. 2022; CCR-22-0301). Having regard to the above, it is an aim of the present invention to provide PARP1 inhibitors, and in particular PARP1 inhibitors for use in medicine. It is a further aim to provide pharmaceutical compositions comprising such inhibitors, and in particular to provide compoundsand pharmaceutical compositions for treating a cancer. It is also an aim to provide methods of synthesis of the compounds. Summary In one aspect, the present invention provides a PARP1 inhibitor compound having a structure of: wherein: a dotted line represents a bond selected from a single bond and a double bond; y is 0,1, or 2; ring D is aromatic or non-aromatic; each XD is independently selected from C, O, and N; with the provisos that: no more than one XD is O; and when an XD is 0 or N, ring D is non-aromatic; each R1 is independently absent, or present and selected from H and a substituted or unsubstituted organic group; each R4 is independently absent or selected from: H; a halogen; C(R9)i, wherein i is an integer in the range 1 to 3; OR9; and S(R9)j, where j is an integer in the range 1 to 5; wherein each R9 is independently selected from H and a substituted or unsubstituted organic group; R2 and R3 are each independently selected from H and a substituted or unsubstituted organic group; and L is a group having a structure of: wherein: X1, X3 X4 and X5 are each independently selected from C and N; each X2 is independently selected from C, N, O, and S; n is 0,1, 2, 3, 4,or 5; m is 0,1, 2, 3, 4,or 5, with the proviso that n + m is in the range 2 to 5; p is 1, 2 or 3; q is 1, 2 or 3, with the proviso that p + q is in the range 2 to 5; r is 0,1, 2, 3, 4,or 5; s is 0,1, 2, 3, 4, or 5, with the proviso that r + s is in the range 2 to 5; each R5A, R5B, and R5C is independently absent or selected from H and a substituted or unsubstituted organic group; R6 is absent or selected from H and a substituted or unsubstituted organic group; and Q is a bond or a linking group having a structure selected from: wherein: t is 0,1, 2, 3, 4 or 5; u is 0,1, 2, 3, 4 and 5, with the proviso that t + u is in the range 0 to 6; and each R7 and R8 is independently selected from H and a substituted or unsubstituted organic group. The PARP1 inhibitor compound may be for use in medicine. For instance, the PARP1 inhibitor compound may be for use in treating a cancer. Another aspect of the invention provides a pharmaceutical composition comprising a PARP1 inhibitor compound as defined herein. A further aspect of the invention provides a pharmaceutical kit for treating a cancer. The pharmaceutical kit comprises a PARP1 inhibitor compound as defined herein, and a further agent for treating cancer. The PARP1 inhibitor compound and the further agent are suitable for administration simultaneously, sequentially or separately. Still another aspect of the invention provides a method of treating a disease and / or a condition and / or a disorder, which method comprises administering to a patient a PARP1 inhibitor compound, a composition or a kit as defined herein. Another aspect of the invention provides a method of synthesising a PARP1 inhibitor compound as defined herein. The method comprises conducting a reaction between: i) a first reactant comprising rings D and E and bearing a first portion of group L, and ii) a second reactant comprising a remainder of group L, to form the PARP1 inhibitor compound. This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This Summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter. Nor is the claimed subject matter limited to implementations that solve any or all of the disadvantages noted herein. Detailed Description General Definitions The verb 'to comprise' is used herein as shorthand for 'to include or to consist of'. In other words, although the verb 'to comprise' is intended to be an open term, the replacement of this term with the closed term 'to consist of' is explicitly contemplated, particularly where used in connection with chemical compositions. It will be appreciated that some compounds disclosed herein may be ionisable, i.e. some compounds may be weak acids, weak bases, or ampholytes. Representations of the free forms of ionisable compounds are intended to encompass the corresponding ionised forms, lonisable compounds may be in free form, or in the form of a pharmaceutically-acceptable salt. A compound is considered to be a PARP1 inhibitor if its presence is capable of preventing or reducing the ability of immobilised PARP1 to undergo auto-poly-ADP ribosylation (AutoPARylation) following incubation with biotinylated-NAD+ as compared to the same process in its absence. Typically, the compound is considered to be a PARP1 inhibitor if it has an IC50 <10 pM in a suitable assay. A suitable assay may be conducted using 2 nM PARP1, 2 pM biotin-NAD+ assay solution in 20 mM HEPES (pH 7.5), 100 mM NaCI, 2 mM DTT, 0.1 % BSA (w / v), 0.02 % Tween (v / v) assay buffer. PARylation may take place for 2 h at room temperature and may be detected using a dissociation-enhanced lanthanide fluorescence immunoassay (DELFIA) readout. A particularly suitable assay is described in the Examples below. Preferably, the compound has an IC50 <1 pM, more preferably <100 nM and most preferably <10 nM in the PARP1 inhibitor assay. A compound is considered to be a selective PARP1 inhibitor if its presence is capable of displacing or reducing the ability of a high affinity Cy5 fluorescent dye-labelled chemical probe to bind to PARP1 whilst displacing the same chemical probe at PARP2 with at least 10-fold weaker activity. Typically, the compound is considered to be a selective PARP1 inhibitor if it has an IC50 <10 pM in this assay at PARP1 with at least 10-fold selectivity preference over PARP2. A suitable such assay may be conducted for 1 h at room temperature using 10 nM PARP1 or PARP2, Tb-cryptate antibody and PARP1 / 2 binding probe in 20 mM HEPES (pH 7.5), 100 mM NaCI, 2 mM DTT, 0.1 % BSA (w / v), 0.02 % Tween (v / v) assay buffer. Probe binding displacement may be detected using homogeneous time-resolved fluorescence. A particularly suitable assay is described in the Examples below. Preferably the selectivity preference of PARP1 over PARP2 is at least 50-fold, more preferably at least 100-fold. A compound is also considered to be a selective PARP1 inhibitor if it has an IC50 <10 pM at PARP1 with at least 10-fold selectivity preference over PARP2 in NanoBRET assays demonstrating cellular target engagement. These assays are based on bioluminescence resonance energy transfer (BRET) between a Nano-luc-tagged protein (e.g. PARP1 or PARP2) and a fluorescent group on a high affinity NAD+ competitive binding probe. Such cellular probe displacement assays can be utilised to measure inhibitor affinities and selectivity ratios at PARP1 and 2. A particularly suitable assay is described in the Examples below. Preferably the selectivity preference of PARP1 over PARP2 is at least 50-fold, more preferably at least 100-fold. The expression "substituted or unsubstituted organic group" is used herein as a synonym for "substituent". Example organic groups are discussed in more detail hereinbelow. Where it is said that an organic group is "substituted", it is meant that an H in the organic group is replaced by a further organic group. A dotted line in a structural formula represents a covalent bond of any appropriate non-zero order, most typically a single bond or a double bond. As will be appreciated, systems comprising multiple double bonds may be conjugated or aromatic. Except where the configuration of a particular bond is directly illustrated, all formulae herein are shown in non-stereoisomeric form and are intended to represent all possible stereoisomers of a particular structure, including all possible isolated enantiomers corresponding to the formula, all possible mixtures of enantiomers corresponding to the formula, all possible mixtures of diastereomers corresponding to the formula, all possible mixtures of epimers corresponding to the formula and all possible racemic mixtures corresponding to the formula. In addition to this, all formulae herein are intended to represent all tautomeric forms equivalent to the corresponding formula. Where stereochemistry is depicted, the stereochemistry shown is relative stereochemistry rather than absolute stereochemistry. The term "aliphatic ring" is used herein in the broad sense of a non-aromatic ring. An aliphatic ring may be carbocylic or heterocyclic, and may be substituted or unsubstituted. Compound numbering Various ones of the compounds provided herein are enantiomeric or diastereomeric. Where a suffix is applied to a compound number, the suffix indicates stereochemistry. A compound number without a suffix denotes a compound having the indicated structural formula without defining stereochemistry. The suffix 'rac' in a compound number denotes a racemic mixture. The suffixes 'cis' and 'trans' denotes compounds which are A ring cis and A ring trans, as explained in the section "stereochemistry" hereinbelow. In the case of diastereomeric compounds, the cis and trans suffixes may refer to pairs of diastereomers having the indicated configuration of the A ring. Nuclear Overhauser Effect nuclear magnetic resonance spectroscopy ("NOE NMR") may be used to determine the stereochemistry of compounds as described herein. The suffix 'a' in a compound number denotes an enantiomer eluted as a first fraction when a mixture of two enantiomers is separated by supercritical fluid chromatography ("SFC") using a chiral column. The suffix 'b' in a compound number denotes an enantiomer eluted as a second fraction when a mixture of two enantiomers is separated by supercritical fluid chromatography ("SFC") using a chiral column. Discussion Provided herein are PARP1 inhibitor compounds having a structure of: a dotted line represents a bond selected from a single bond and a double bond; y is 0,1, or 2; ring D is aromatic or non aromatic; each XD is independently selected from C, O, and N; with the provisos that: 10 no more than one XD is O; and when an XD is O or N, ring D is non-aromatic; each R1 is independently absent, or present and selected from H and a substituted or unsubstituted organic group; each R4 is independently absent or selected from: H; a halogen; C(R9)i, wherein i is an integer in the range 1 to 3; OR9; and S(R9)j, where j is an integer in the range 1 to 5; wherein each R9 is independently selected from H and a substituted or unsubstituted organic group; r2 anc| are each independently selected from H and a substituted or unsubstituted organic group; and X1, X3, X4 and X5 are each independently selected from C and N; each X2 is independently selected from C, N, O, and S; n is 0,1, 2, 3, 4,or 5; m is 0,1, 2, 3,4,or 5, with the proviso that n + m is in the range 2 to 5; p is 1, 2 or 3; q is 1, 2 or 3, with the proviso that p + q is in the range 2 to 5; r is 0,1, 2, 3, 4,or 5; s is 0,1, 2, 3,4, or 5, with the proviso that r + s is in the range 2 to 5; each R5A, R5B, and R5C is independently absent or selected from H and a substituted or unsubstituted organic group; R6 is absent or selected from H and a substituted or unsubstituted organic group; and Q is a bond or a linking group having a structure selected from: wherein: t is 0,1, 2, 3, 4 or 5; u is 0,1, 2, 3, 4 and 5, with the proviso that t + u is in the range 0 to 6; and each R7 and R8 is independently selected from H and a substituted or unsubstituted organic group. The PARP1 inhibitor compounds provided herein may be selective for PARP1 over PARP2. Various aspects of the above general structure will now be discussed in more detail. Stereochemistry Some of the PARP1 inhibitor compounds provided herein include one or more chiral centres. Such compounds may be provided in the form of an isolated enantiomer; a mixture of two or more enantiomers; a mixture of two or more diastereomers or epimers; or a racemic mixture. Some PARP1 inhibitor compounds may be capable of tautomerism. Such compounds may be provided in the form of any possible tautomer. When ring A of the PARP1 inhibitor compounds is a cycloalkane, the compound may exhibit cis-trans isomerism. In the context of the present disclosure, unless expressly stated otherwise, a "cis" compound has a cis configuration across ring A: And a "trans" compound has a trans configuration across ring A: Substituents - general 5 The expression "R5 group" refers generically to groups R5A, R5B, and R5C. An "R5A" group is an R5 group which is attached to ring A, and so on. Some of the formulae presented herein use more specific identifiers for R5 groups. For example, "R5A1" identifies a subset of R5A groups. 10 The expression "X atom" refers generically to any variable ring atom (XD, X1, X2, X3, X4, X5). In the compounds provided herein, R6 and various ones of the R1, R4, and R5 groups may be absent. Dotted lines in the structural formulae presented herein representing covalent bonds of any non-zero order. 15 As will be appreciated, the number of ring bonds and the number of substituents are selected such that the atoms of the rings maintain a stable valency. Maintaining a stable valency means ensuring that an atom has its normal (typically most common) valency in organic compounds (i.e. 2 for oxygen; 2 or 6 for sulfur; 3 or 4 for nitrogen; and 4 for carbon). When an X atom is N, that atom most preferably has a valency of 3. Compounds containing tetravalent N atoms are also contemplated. Preferably, the PARP1 inhibitor compound includes at most one tetravalent N, and more preferably no tetravalent N atoms. The PARP1 inhibitor compounds are typically free of 0-0 bonds. When an X atom is O, its two immediately adjacent ring atoms are not 0. When an X atom is S, its corresponding Rgroups may both be absent or selected from =0 and =NR10, where R10 is H or a substituted or unsubstituted organic group, preferably a Cl to C3 alkyl group. Each R1, R4 and R5 group may independently be absent or present, and may be the same or different. The substituents (i.e. R groups; R1, R2, R4, R5, R6, R7, and R8) are not especially limited, provided that they do not prevent the PARP1 inhibitory function from occurring. The substituents are selected from H and a substituted or unsubstituted organic group. Thus, both above and in the following, the terms 'substituent' and 'organic group' are not especially limited and may be any functional group or any atom, especially any functional group or atom common in organic chemistry. Any R5 or R6 group may form a ring with any other R5 or R6 group on an adjacent and / or proximal atom, although in most embodiments this is not preferred, except where explicitly stated. Thus, the following substituents may together form a ring: an R5A with another R5A; an R5B with another R5B; an R5C with another R5C; or an R5C with R6. In the present context, an adjacent and / or proximal atom may mean another atom directly bonded to an atom (adjacent) or may be two atoms with only a single atom in between (proximal), or may mean two atoms close enough sterically to be capable of forming a ring (proximal). Preferably R5 / R6 groups attached to the same atom do not together form a ring, although this is not excluded. A single R1, R4, R5 or R6 group on an atom, or two R1 / R4 / R5 groups on the same atom, may form a group which is double bonded to that atom. Accordingly, an R1, R4, R5 or R6 group, or two R1 / R4 / R5 groups attached to the same atom, may together form a =0 group, or a =C(R')2 group (wherein each R' group is the same or different and is H or an organic group, preferably H or a straight or branched Ci-Ce alkyl group). This is more typical in cases where the R groups are attached to a C atom, such that together they form a C=O group or a C=C(R')2 group. Thus in some cases an X2 group which is C may bear a =0 group. For example, a pair of R5A groups attached to the same atom may together represent a carbonyl group. Likewise, a pair of R4 groups attached to the same atom may together represent a carbonyl group. 'Substituent' and 'organic group' may have any of the following meanings. The organic group may comprise any one or more atoms from any of groups IHA, IVA, VA, VIA or VIIA of the Periodic Table, such as a B, Si, N, P, O, or S atom (e.g. OH, OR, NH2, NHR, NR2, SH, SR, SO2R, SO3H, PO4H2) or a halogen atom (e.g. F, Cl, Br or I) where R is a linear or branched lower hydrocarbon (1-6 C atoms) or a linear or branched higher hydrocarbon (7 C atoms or more, e.g. 7-40 C atoms). The organic group preferably comprises a hydrocarbon group. The hydrocarbon group may comprise a straight chain, a branched chain or a cyclic group. Independently, the hydrocarbon group may comprise an aliphatic or an aromatic group. Also independently, the hydrocarbon group may comprise a saturated or unsaturated group. When the hydrocarbon comprises an unsaturated group, it may comprise one or more alkene functionalities and / or one or more alkyne functionalities. When the hydrocarbon comprises a straight or branched chain group, it may comprise one or more primary, secondary and / or tertiary alkyl groups. When the hydrocarbon comprises a cyclic group it may comprise an aromatic ring, a nonaromatic ring, an aliphatic ring, a heterocyclic group, and / or fused ring derivatives of these groups. The ring may be fully saturated, partially saturated, or fully unsaturated. The cyclic group may thus comprise a benzene, naphthalene, anthracene, phenanthrene, phenalene, biphenylene, pentalene, indene, as-indacene, s-indacene, acenaphthylene, fluorene, fluoranthene, acephenanthrylene, azulene, heptalene, pyrrole, pyrazole, imidazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole, pyrrolidine, furan, oxetane, tetrahydrofuran, 2-aza-tetrahydrofuran, 3-aza-tetrahydrofuran, oxazole, isoxazole, furazan, 1,2,4-oxadiazol, 1,3,4-oxadiazole, thiophene, isothiazole, thiazole, thiolane, pyridine, pyridazine, pyrimidine, pyrazine, piperidine, 2-azapiperidine, 3-azapiperidine, piperazine, pyran, tetra hydro pyran, 2-azapyran, 3-azapyran, 4-azapyran, 2-aza-tetrahydropyran, 3-aza-tetrahydropyran, morpholine, thiopyran, 2-azathiopyran, 3-azathiopyran, 4-azathiopyran, thiane, indole, indazole, benzimidazole, 4-azaindole, 5-azaindole, 6-azaindole, 7-azaindole, isoindole, 4-azaisoindole, 5-azaisoindole, 6-azaisoindole, 7-azaisoindole, indolizine, 1-azaindolizine, 2-azaindolizine, 3-azaindolizine, 5-azaindolizine, 6-azaindolizine, 7-azaindolizine, 8-azaindolizine, 9-azaindolizine, purine, carbazole, carboline, benzofuran, isobenzofuran, benzothiophene, isobenzothiophene, quinoline, cinnoline, quinazoline, quinoxaline, 5-azaquinoline, 6-azaquinoline, 7-azaquinoline, isoquinoline, phthalazine, 6-azaisoquinoline, 7-azaisoquinoline, pteridine, chromene, isochromene, acridine, phenanthridine, perimidine, phenanthroline, phenoxazine, xanthene, phenoxanthiin, and / or thianthrene, as well as regioisomers of the above groups. These groups may generally be attached at any point in the group, and also may be attached at a hetero-atom or at a carbon atom. In some instances particular attachment points are preferred, such as at 1-yl, 2-yl and the like, and these are specified explicitly where appropriate. All tautomeric ring forms are included in these definitions. For example pyrrole is intended to include 1 / 7-pyrrole, 2 / 7-pyrrole and 3H-pyrrole. The number of carbon atoms in the hydrocarbon group is not especially limited, but preferably the hydrocarbon group comprises from 1-40 C atoms. The hydrocarbon group may thus be a lower hydrocarbon (1-6 C atoms) or a higher hydrocarbon (7 C atoms or more, e.g. 7-40 C atoms). The lower hydrocarbon group may be a methyl, ethyl, propyl, butyl, pentyl or hexyl group or regioisomers of these, such as isopropyl, isobutyl, tert-butyl, etc. The number of atoms in the ring of the cyclic group is not especially limited, but preferably the ring of the cyclic group comprises from 3-10 atoms, such as 3, 4, 5, 6, 7, 8, 9 or 10 atoms. The groups comprising heteroatoms described above, as well as any of the other groups defined above, may comprise one or more heteroatoms from any of groups IHA, IVA, VA, VIA or VIIA of the Periodic Table, such as a B, Si, N, P, O, or S atom or a halogen atom (e.g. F, Cl, Br or I). Thus, the substituent may comprise one or more of any of the common functional groups in organic chemistry, such as hydroxy groups, carboxylic acid groups, ester groups, ether groups, aldehyde groups, ketone groups, amine groups, amide groups, imine groups, thiol groups, thioether groups, sulfate groups, sulfonic acid groups, sulfonyl groups, and phosphate groups etc. The substituent may also comprise derivatives of these groups, such as carboxylic acid anhydrides and carboxylic acid halides. In addition, any substituent may comprise a combination of two or more of the substituents and / or functional groups defined herein. Where it is said that a substituent (R1, R2, R3, R4, R5A(e.g. R5A1, R5A2, R5A3), R5B, R5C, R6, R7, R8, R51, and / or R52) is a substituted or unsubstituted organic group, the or each substituted or unsubstituted organic group may in particular be independently selected from: deuterium; a halogen (such as -F, -Cl, -Br and -I); a nitrile group; a substituted or unsubstituted linear or branched Ci-Ce alkyl group (such as Me, Et, Pr, i-Pr, n-Bu, i-Bu, t-Bu, pentyl and hexyl); a substituted or unsubstituted linear or branched Ci-Ce alkyl-aryl group (such as -CH2Ph, -CH2(2,3 or 4)F-Ph, -CH2(2,3 or 4)CI-Ph, -CH2(2,3 or 4)Br-Ph, -CH2(2,3 or4)l-Ph, -CH2CH2Ph, -CH2CH2CH2Ph, -CH2CH2CH2CH2Ph, -CH2CH2CH2CH2CH2Ph, and -CH2CH2CH2CH2CH2CH2Ph); a substituted or unsubstituted linear or branched Ci-Ce halogenated alkyl group (such as -CH2F, -CH2CI, -CH2Br, -CH2I, -CHF2, -CF3, -CCI3 -CBr3, -Cl3, -CH2CH2F, -CH2CF3, -CH2CCI3, -CH2CBr3, and -CH2CI3); NH2 or a substituted or unsubstituted linear or branched primary secondary or tertiary Ci-Ce amine group (such as -NMeH, -NMe2, -NEtH, -NEtMe, -NEt2, -NPrH, -NPrMe, -NPrEt, -NPr2, -NBuH, -NBuMe, -NBuEt, —CH2-NH2, -CH2-NMeH, -CH2-NMe2, -CH2-NEtH, -CH2-NEtMe, -CH2-NEt2, -CH2-NPrH, -CH2-NPrMe, and -CH2-NPrEt); a substituted or unsubstituted amino-aryl group (such as -NH-Ph, -NH-(2,3 or4)F-Ph, -NH-(2,3 or4)CI-Ph, -NH-(2,3 or4)Br-Ph, -NH-(2,3 or 4)I-Ph, -NH-(2,3 or 4)Me-Ph, -NH-(2,3 or 4)Et-Ph, -NH-(2,3 or4)Pr-Ph, -NH-(2,3 or4)Bu-Ph, NH-(2,3 or 4)OMe-Ph, -NH-(2,3 or 4)0Et-Ph, -NH-(2,3 or 4)0Pr-Ph, -NH-(2,3 or 4)OBu-Ph, -NH-2,(3,4,5 or 6)F2-Ph, -NH-2,(3,4,5 or 6)CI2-Ph, -NH-2,(3,4,5 or 6)Br2-Ph, -NH-2,(3,4,5 or 6)I2-Ph, -NH-2,(3,4,5 or 6)Me2-Ph, -NH-2,(3,4,5 or 6)Et2-Ph, -NH-2,(3,4,5, or 6)Pr2-Ph, -NH-2,(3,4,5 or 6)Bu2-Ph), a substituted or unsubstituted cyclic amine or amido group (such as pyrrolidin-l-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-l-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, 2-keto-pyrrolidinyl, 3-keto-pyrrolidinyl, 2-keto-piperidinyl, 3-keto-piperidinyl, and 4-keto-piperidinyl); a substituted or unsubstituted cyclic C3-C8 alkyl group (such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl); an -OH group; a substituted or unsubstituted linear or branched Ci-Ce alcohol group (such as-CH2OH, -CH2CH2OH, -CH(CH3)CH2OH, -C(CH3)2OH, -CH2CH2CH2OH, -CH2CH2CH2CH2OH, -CH(CH3)CH2CH2OH, -CH(CH3)CH(CH3)OH, -CH(CH2CH3)CH2OH, -C(CH3)2CH2OH, -CH2CH2CH2CH2CH2OH, and -CH2CH2CH2CH2CH2CH2OH); a substituted or unsubstituted linear or branched Ci-Ce carboxylic acid group (such as -COOH, -CH2COOH, -CH2CH2COOH, -CH2CH2CH2COOH, -CH2CH2CH2CH2COOH, and -CH2CH2CH2CH2CH2COOH); a substituted or unsubstituted linear or branched carbonyl group (such as -(CO)Me, -(CO)Et, -(CO)Pr, -(CO)iPr, -(CO)nBu, -(CO)iBu, -(CO)tBu, -(CO)Ph, -(CO)CH2Ph, -(CO)CH2OH, -(CO)CH2OCH3, -(CO)CH2NH2, -(CO)CH2NHMe, -(CO)CH2NMe2, -(CO)-cyclopropyl, -(CO)-l,3-epoxypropan-2-yl; -(CO)NH2, -(CO)NHMe, -(CO)NMe2, -(CO)NHEt, -(CO)NEt2, -(CO)-pyrollidine-N-yl, -(CO)-morpholine-N-yl, -(CO)-piperazine-N-yl, -(CO)-N-methyl-piperazine-N-yl, -(CO)NHCH2CH2OH, -(CO)NHCH2CH2OMe, -(CO)NHCH2CH2NH2, -(CO)NHCH2CH2NHMe, and -(CO)NHCH2CH2NMe2); a substituted or unsubstituted linear or branched Ci-Ce carboxylic acid ester group (such as -COOMe, -COOEt, -COOPr, -COO-i-Pr, -COO-n-Bu, -COO-i-Bu, -COO-t-Bu, -CH2COOMe, -CH2CH2COOMe, -CH2CH2CH2COOMe, and -CH2CH2CH2CH2COOMe); a substituted or unsubstituted linear or branched Ci-Ce amide group (such as -CO-NH2, -CO-NMeH, -CO-NMe2, -CO-NEtH, -CO-NEtMe, -CO-NEt2, -CO-NPrH, -CO-NPrMe, and -CO-NPrEt); a substituted or unsubstituted linear or branched C1-C7 amino carbonyl group (such as -NH-CO-Me, -NH-CO-Et, -NH-CO-Pr, -NH-CO-Bu, -NH-CO-pentyl, -NH-CO-hexyl, -NH-CO-Ph, -NMe-CO-Me, -NMe-CO-Et, -NMe-CO-Pr, -NMe-CO-Bu, -NMe-CO-pentyl, -NMe-CO-hexyl, -NMe-CO-Ph); a substituted or unsubstituted linear or branched C1-C7 alkoxy or aryloxy group (such as -OMe, -OEt, -OPr, -O-i-Pr, -O-n-Bu, -O-i-Bu, -O-t-Bu, -O-pentyl, -O-hexyl, -OCH2F, -OCHF2, -OCF3, -OCH2CI, -OCHCI2, -OCCI3, -O-Ph, -O-CH2-Ph, -O-CH2-(2,3 or 4)-F-Ph, -O-CH2-(2,3 or 4)-CI-Ph, -CH2OMe, -CH2OEt, -CH2OPr, -CH2OBu, -CH2CH2OMe, -CH2CH2CH2OMe, -CH2CH2CH2CH2OMe, and -CH2CH2CH2CH2CH2OMe); a substituted or unsubstituted linear or branched aminoalkoxy group (such as-OCH2NH2, -OCH2NHMe, -OCH2NMe2, -OCH2NHEt, -OCH2NEt2, -OCH2CH2NH2, -OCH2CH2NHMe, -OCH2CH2NMe2, -OCH2CH2NHEt, and -OCH2CH2NEt2); a substituted or unsubstituted sulfonyl group (such as -SO2Me, -SO2Et, -SO2Pr, -SO2iPr, -SO2Ph, -SO2-(2,3 or 4)-F-Ph, -SO2-cyclopropyl, -SO2CH2CH2OCH3, -SO2NH2, -SO2NHMe, -SO2NMe2, -SO2NHEt, -SO2NEt2, -SO2-pyrrolidine-N-yl, -SO2-morpholine-N-yl, -SO2NHCH2OMe,and -SO2NHCH2CH2OMe); a substituted or unsubstituted aminosulfonyl group (such as -NHSO2Me, -NHSO2Et, - NHSO2Pr, -NHSO2iPr, -NHSO2Ph, -NHSO2-(2,3 or4)-F-Ph, -NHSO2-cyclopropyl, -NHSO2CH2CH2OCH3); a substituted or unsubstituted aromatic group (such as Ph-, 2-F-Ph-, 3-F-Ph-, 4-F-Ph-, 2-CI-Ph-, 3-CI-Ph-, 4-CI-Ph-, 2-Br-Ph-, 3-Br-Ph-, 4-Br-Ph-, 2-l-Ph-, 3-l-Ph, 4-l-Ph-, 2,(3,4,5 or 6)-F2-Ph-, 2,(3,4,5 or 6)-CI2-Ph-, 2,(3,4,5 or 6)-Br2-Ph-, 2,(3,4,5 or 6)-l2-Ph-, 2,(3,4,5 or 6)-Me2-Ph-, 2,(3,4,5 or 6)-Et2-Ph-, 2,(3,4,5 or 6)-Pr2-Ph-, 2,(3,4,5 or 6)-Bu2-Ph-, 2,(3,4,5 or 6)-(CN)2-Ph-, 2,(3,4,5 or 6)-(NO2)2-Ph-, 2,(3,4,5 or 6)-(NH2)2-Ph-, 2,(3,4,5 or 6)-(MeO)2-Ph-, 2,(3,4,5 or 6)-(CF3)2-Ph-, 3,(4 or 5)-F2-Ph-, 3,(4 or 5)-CI2-Ph-, 3,(4 or 5)-Br2-Ph-, 3,(4 or 5)-l2-Ph-, 3,(4 or 5)-Me2-Ph-, 3,(4 or 5)-Et2-Ph-, 3,(4 or 5)-Pr2-Ph-, 3,(4 or 5)-Bu2-Ph-, 3,(4 or 5)-(CN)2-Ph-, 3,(4 or 5)-(NO2)2-Ph-, 3,(4 or 5)-(NH2)2-Ph-, 3,(4 or 5)-(MeO)2-Ph-, 3,(4 or 5)-(CF3)2-Ph-, 2-Me-Ph-, 3-Me-Ph-, 4-Me-Ph-, 2-Et-Ph-, 3-Et-Ph-, 4-Et-Ph-, 2-Pr-Ph-, 3-Pr-Ph-, 4-Pr-Ph-, 2-Bu-Ph-, 3-Bu-Ph-, 4-Bu-Ph-, 2-(CN)-Ph-, 3-(CN)-Ph-, 4-(CN)-Ph-, 2-(NO2)-Ph-, 3-(NO2)-Ph-, 4-(NO2)-Ph-, 2-(NH2)-Ph-, 3-(NH2)-Ph-, 4-(NH2)-Ph-, 2-MeO-Ph-, 3-MeO-Ph-, 4-MeO-Ph-, 2-(NH2-CO)-Ph-, 3-(NH2-CO)-Ph-, 4-(NH2-CO)-Ph-, 2-CF3-Ph-, 3-CF3-Ph-, 4-CF3-Ph-, 2-CF3O-Ph-, 3-CF3O-Ph-, and 4-CF3O-Ph-); a saturated or unsaturated, substituted or unsubstituted, heterocyclic group, optionally an aromatic heterocyclic group or a non-aromatic heterocyclic group (such as pyrrole-l-yl, pyrrole-2-yl, pyrrole-3-yl, pyrazole-l-yl, pyrazole-3-yl, pyrazole-4-yl, pyrazole-5-yl, imidazole-l-yl, imidazole-2-yl, imidazole-4-yl, imidazole-5-yl, 1,2,3-triazole-l-yl, l,2,3-triazole-4-yl, l,2,3-triazole-5-yl, 1,2,4-triazole-l-yl, l,2,4-triazole-3-yl, l,2,4-triazole-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazine-3-yl, pyridazine-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrimidin-6-yl, pyrazine-2-yl, pyrrolidine-l-yl, pyrrolidine-2-yl, pyrrolidine-3-yl, piperidine-l-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, 2-azapiperidine-l-yl, 2-azapiperidine-3-yl, 2-azapiperidine-4-yl, 3-azapiperidine-l-yl, 3-azapiperidine-2-yl, 3-azapiperidine-4-yl, 3-azapiperidine-5-yl, piperazine-l-yl, piperazine-2-yl, furan-2-yl, furan-3-yl, pyran-2-yl, pyran-3-yl, pyran-4-yl, 2-azapyran-2-yl, 2-azapyran-3-yl, 2-azapyran-4-yl, 2-azapyran-5-yl, 2-azapyran-6-yl, 3-azapyran-2-yl, 3-azapyran-4-yl, 3-azapyran-5-yl, 3-azapyran-6-yl, 4-azapyran-2-yl, 4-azapyran-3-yl, 4-azapyran-4-yl, 4-azapyran-5-yl, 4-azapyran-6-yl, oxetan-2-yl, oxetan-3-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-2-yl, 2-aza-tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-4-yl, 2-aza-tetrahydrofuran-5-yl, 3-aza-tetrahydrofuran-2-yl, 3-aza-tetrahydrofuran-3-yl, 3-aza-tetrahydrofuran-4-yl, 3-aza-tetrahydrofuran-5-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, 2-aza-tetrahydropyran-2-yl, 2-aza-tetrahydropyran-3-yl, 2-aza-tetrahydropyran-4-yl, 2-aza-tetrahydropyran-5-yl, 2-aza-tetrahydropyran-6-yl, 3-aza-tetrahydropyran-2-yl, 3-aza-tetrahydropyran-3-yl, 3-aza-tetrahydropyran-4-yl, 3-aza-tetrahydropyran-5-yl, 3-aza-tetrahydropyran-6-yl, morpholine-2-yl, morpholine-3-yl, morpholine-4-yl, thiophen-2-yl, thiophen-3-yl, isothiazole-3-yl, isothiazole-4-yl, isothiazole-5-yl, thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, thiopyran-2-yl, thiopyran-3-yl, thiopyran-4-yl, 2-azathiopyran-2-yl, 2-azathiopyran-3-yl, 2-azathiopyran-4-yl, 2-azathiopyran-5-yl, 2-azathiopyran-6-yl, 3-azathiopyran-2-yl, 3-azathiopyran-4-yl, 3-azathiopyran-5-yl, 3-azathiopyran-6-yl, 4-azathiopyran-2-yl, 4-azathiopyran-3-yl, 4-azathiopyran-4-yl, 4-azathiopyran-5-yl, 4-azathiopyran-6-yl, thiolane-2-yl, thiolane-3-yl, thiane-2-yl, thiane-3-yl, thiane-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, furazan-3-yl, (l,3,4-oxadiazol)-2-yl, (l,3,4-oxadiazol)-5-yl, (l,2,4-oxadiazol)-3-yl, (l,2,4-oxadiazol)-5-yl; and tetrazole-l-yl, tetrazole-2-yl, tetrazole-5-yl). With the exception of R4, pairs of substituent groups with matching identifiers may together form a ring. For example, a pair of substituent groups attached to different atoms of the same ring may be connected to form a ring. A pair of R5A groups attached to different atoms may together form a ring with ring A atoms. A pair of R5B groups attached to different atoms may together form a ring with ring B atoms. A pair of R5C groups attached to different atoms may together form a ring with ring C atoms. It is also contemplated that an R5C group and an R6 group attached to different atoms may together form a ring with ring C atoms. Preferably, each R5 group (R5A, R5B, R5C) is independently absent or selected from: H, deuterium, a halogen (such as -F, -Cl, -Br, and -I; preferably F or Cl), a nitrile group, a CrC6 alkyl group, a Ci-Ce halogenated alkyl group (preferably CF3 or CHF2), a cyclopropyl group, an -OH group, a Ci-Ce alcohol group, a C1-C7 amino carbonyl group (such as -NH-CO-Me), an -NH2 group, a Ci-Ce amino group, and a Ci-Ce alkoxy group. When a pair of R5 groups forms a ring, the pair of R5 groups may together represent a group selected from -CH2-, -CH2CH2-, -CH=CH-CH=CH-, or -NH-CO-NH-. In particular, it is contemplated that two R5A groups may together represent an alkyl group bridging ring A. Various ones of the substituent groups may be bonded to a nitrogen atom. For example, when Q is: R8 is bonded to a nitrogen. In some instances, an R1, R4, or R5A or R5B group may be attached to a ring atom which is N; and R3 is attached to an N. The preferred substituents for N atoms are: H; a substituted or unsubstituted linear or branched Ci-Ce alkyl group (such as Me, Et, Pr, i-Pr, n-Bu, i-Bu, t-Bu, pentyl and hexyl); a substituted or unsubstituted linear or branched Ci-Ce alkyl-aryl group (such as -CH2Ph, -CH2(2,3 or 4)F-Ph, -CH2(2,3 or 4)CI-Ph, -CH2(2,3 or 4)Br-Ph, -CH2(2,3 or4)l-Ph, -CH2CH2Ph, -CH2CH2CH2Ph, -CH2CH2CH2CH2Ph, -CH2CH2CH2CH2CH2Ph, and -CH2CH2CH2CH2CH2CH2Ph); a substituted or unsubstituted linear or branched Ci-Ce halogenated alkyl group (such as -CH2F, -CF3, -CH2CH2F and -CH2CF3); a substituted or unsubstituted cyclic amine or amido group (such as pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, 2-keto-pyrrolidinyl, 3-keto-pyrrolidinyl, 2-keto-piperidinyl, 3-keto-piperidinyl, and 4-keto-piperidinyl); a substituted or unsubstituted cyclic C3-Cs alkyl group (such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl); a substituted or unsubstituted linear or branched C2-Ce alcohol group (such as -CH2CH2OH, -CH(CH3)CH2OH, -C(CH3)2OH, -CH2CH2CH2OH, -CH2CH2CH2CH2OH, -CH(CH3)CH2CH2OH, -CH(CH3)CH(CH3)OH, -CH(CH2CH3)CH2OH, -C(CH3)2CH2OH, -ch2ch2ch2ch2ch2oh, and -CH2CH2CH2CH2CH2CH2OH); a substituted or unsubstituted linear or branched C2-C6 carboxylic acid group (such as -CH2COOH, -CH2CH2COOH, -CH2CH2CH2COOH, -CH2CH2CH2CH2COOH, and -CH2CH2CH2CH2CH2COOH); a substituted or unsubstituted linear or branched carbonyl group (such as -(CO)Me, -(CO)Et, -(CO)Pr, -(CO)-i_Pr, -(CO)-n-Bu, -(CO)-i-Bu, -(CO)-t-Bu, -(CO)Ph, -(CO)CH2Ph, -(CO)CH2OH, -(CO)CH2OCH3, -(CO)CH2NH2, -(CO)CH2NHMe, -(CO)CH2NMe2, -(CO)-cyclopropyl, -(CO)-l,3-epoxypropan-2-y I; -(CO)NH2, -(CO)NHMe, -(CO)NMe2, -(CO)NHEt, -(CO)NEt2, -(CO)-pyrollidine-N-yl, -(CO)-morpholine-N-yl, -(CO)-piperazine-N-yl, -(CO)-N-methyl-piperazine -N-yl, -(CO)NHCH2CH2OH, -(CO)NHCH2CH2OMe, -(CO)NHCH2CH2NH2, -(CO)NHCH2CH2NHMe, and -(CO)NHCH2CH2NMe2); a substituted or unsubstituted linear or branched Ci-Ce carboxylic acid ester group (such as -COOMe, -COOEt, -COOPr, -COO-i-Pr, -COO-n-Bu, -COO-i-Bu, -COO-t-Bu, -CH2COOMe, -CH2CH2COOMe, -CH2CH2CH2COOMe, and -CH2CH2CH2CH2COOMe); a substituted or unsubstituted linear or branched Ci-Ce amide group (such as -CO-NH2, -CO-NMeH, -CO-NMe2, -CO-NEtH, -CO-NEtMe, -CO-NEt2, -CO-NPrH, -CO-NPrMe, and -CO-NPrEt); a substituted or unsubstituted sulfonyl group (such as -SO2Me, -SO2Et, -SO2Pr, -SO2iPr, -SO2Ph, -SO2-(2,3 or 4)-F-Ph, -SO2-cyclopropyl, -SO2CH2CH2OCH3), -SO2NH2, -SO2NHMe, -SO2NMe2, -SO2NHEt, -SO2NEt2, -SO2-pyrrolidine-N-yl, -SO2-morpholine-N-yl, -SO2NHCH2OMe, and -SO2NHCH2CH2OMe); a substituted or unsubstituted aromatic group (such as Ph-, 2-F-Ph-, 3-F-Ph-, 4-F-Ph-, 2-CI-Ph-, 3-CI-Ph-, 4-CI-Ph-, 2-Br-Ph-, 3-Br-Ph-, 4-Br-Ph-, 2-1 -Ph-, 3-l-Ph, 4-l-Ph-, 2,(3,4,5 or 6)-F2-Ph-, 2,(3,4,5 or 6)-CI2-Ph-, 2,(3,4,5 or 6)-Br2-Ph-, 2,(3,4,5 or 6)-l2-Ph-, 2,(3,4,5 or 6)-Me2-Ph-, 2,(3,4,5 or 6)-Et2-Ph-, 2,(3,4,5 or 6)-Pr2-Ph-, 2,(3,4,5 or 6)-Bu2-Ph-, 2,(3,4,5 or 6)-(CN)2-Ph-, 2,(3,4,5 or 6)-(NO2)2-Ph-, 2,(3,4,5 or 6)-(NH2)2-Ph-, 2,(3,4,5 or 6)-(MeO)2-Ph-, 2,(3,4,5 or 6)-(CF3)2-Ph-, 3,(4 or 5)-F2-Ph-, 3,(4 or 5)-CI2-Ph-, 3,(4 or 5)-Br2-Ph-, 3,(4 or 5)-12-Ph-, 3,(4 or 5)-Me2-Ph-, 3,(4 or 5)-Et2-Ph-, 3,(4 or 5)-Pr2-Ph-, 3,(4 or 5)-Bu2-Ph-, 3,(4 or 5)-(CN)2-Ph-, 3,(4 or 5)-(NO2)2-Ph-, 3,(4 or 5)-(NH2)2-Ph-, 3,(4 or 5)-(MeO)2-Ph-, 3,(4 or 5)-(CF3)2-Ph-, 2-Me-Ph-, 3-Me-Ph-, 4-Me-Ph-, 2-Et-Ph-, 3-Et-Ph-, 4-Et-Ph-, 2-Pr-Ph-, 3-Pr-Ph-, 4-Pr-Ph-, 2-Bu-Ph-, 3-Bu-Ph-, 4-Bu-Ph-, 2-(CN)-Ph-, 3-(CN)-Ph-, 4-(CN)-Ph-, 2-(NO2)-Ph-, 3-(NO2)-Ph-, 4-(NO2)-Ph-, 2-(NH2)-Ph-, 3-(NH2)-Ph-, 4-(NH2)-Ph-, 2-MeO-Ph-, 3-MeO-Ph-, 4-MeO-Ph-, 2-(NH2-CO)-Ph-, 3-(NH2-CO)-Ph-, 4-(NH2-CO)-Ph-, 2-CF3-Ph-, 3-CF3-Ph-, 4-CF3-Ph-, 2-CF3O-Ph-, 3-CF3O-Ph-, and 4-CF3O-Ph-); and a substituted or unsubstituted heterocyclic group (such as pyrrole-2-yl, pyrrole-3-yl, pyrazole-3-yl, pyrazole-4-yl, pyrazole-5-yl, imidazole-2-yl, imidazole-4-yl, imidazole-5-yl, l,2,3-triazole-4-yl, l,2,3-triazole-5-yl, l,2,4-triazole-3-yl, l,2,4-triazole-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazine-3-yl, pyridazine-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrimidin-6-yl, pyrazine-2-yl, pyrrolidine-2-yl, pyrrolidine-3-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, 2-azapiperidine-3-yl, 2-azapiperidine-4-yl, 3-azapiperidine-2-yl, 3-azapiperidine-4-yl, 3-azapiperidine-5-yl, piperazine-2-yl, furan-2-yl, furan-3-yl, pyran-2-yl, pyran-3-yl, pyran-4-yl, 2-azapyran-3-yl, 2-azapyran-4-yl, 2-azapyran-5-yl, 2-azapyran-6-yl, 3-azapyran-2-yl, 3-azapyran-4-yl, 3-azapyran-5-yl, 3-azapyran-6-yl, 4-azapyran-2-yl, 4-azapyran-3-yl, 4-azapyran-5-yl, 4-azapyran-6-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-4-yl, 2-aza-tetrahydrofuran-5-yl, 3-aza-tetrahydrofuran-2-yl, 3-aza-tetrahydrofuran-4-yl, 3-aza-tetrahydrofuran-5-yl, tetrahydropyran-2-yl, oxetan-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, 2-aza-tetrahydropyran-3-yl, 2-aza-tetrahydropyran-4-yl, 2-aza-tetrahydropyran-5-yl, 2-aza-tetrahydropyran-6-yl, 3-aza-tetrahydropyran-2-yl, 3-aza-tetrahydropyran-4-yl, 3-aza-tetrahydropyran-5-yl, 3-aza-tetrahydropyran-6-yl, morpholine-2-yl, morpholine-3-yl, thiophen-2-yl, thiophen-3-yl, isothiazole-3-yl, isothiazole-4-yl, isothiazole-5-yl, thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, thiopyran-2-yl, thiopyran-3-yl, thiopyran-4-yl, 2-azathiopyran-3-yl, 2-azathiopyran-4-yl, 2-azathiopyran-5-yl, 2-azathiopyran-6-yl, 3-azathiopyran-2-yl, 3-azathiopyran-4-yl, 3-azathiopyran-5-yl, 3-azathiopyran-6-yl, 4-azathiopyran-2-yl, 4-azathiopyran-3-yl, 4-azathiopyran-5-yl, 4-azathiopyran-6-yl, thiolane-2-yl, thiolane-3-yl, thiane-2-yl, thiane-3-yl, thiane-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, furazan-3-yl, (l,3,4-oxadiazol)-2-yl, (l,3,4-oxadiazol)-5-yl, (l,2,4-oxadiazol)-3-yl, (l,2,4-oxadiazol)-5-yl; and tetrazole-5-yl). Optionally, R8, or any R1, R4, or R5A or R5B that is attached to a ring nitrogen, may preferably be selected from H, a substituted or unsubstituted linear or branched Ci-Ce alkyl group, and a substituted or unsubstituted linear or branched Ci-Ce halogenated alkyl group. An R1 or R4 attached to a N is preferably selected from H, a Cl to C3 alkyl group, and a Cl to C3 fluoroalkyl group, such as CH2CF3. Head group - general The head group of the PARP1 inhibitor compound comprises rings D and E, as shown in the general formula below: A dotted line represents a bond selected from a single bond and a double bond. Ring D may be a saturated ring, an unsaturated non-aromatic ring, or an aromatic ring. y is 0,1, or 2. In other words, ring D may be a 5-, 6-, or 7-membered ring. In particular, ring D may be a 5-membered ring (y=0) or a 6-membered ring (y=l). Compounds having 6-membered D-rings (y=l) are particularly preferred. Each individual XD is selected from C, O, and N. No more than one XD is O. When an XD is O or N, ring D is non-aromatic. Optionally, each XD is C. Each R1 is independently absent, H, or a substituted or unsubstituted organic group. Each R4 is independently absent or selected from: H; a halogen; C(R9)i, wherein i is an integer in the range 1 to 3; OR9; and S(R9)j, where j is an integer in the range 1 to 5. Each R9 is independently selected from H and a substituted or unsubstituted organic group. When R4 is C(R9), and i is 1, R9 may be a nitrile nitrogen, J Each R1 and each R4 may in particular be absent or selected from: H; a halogen; a nitrile group; a Cl to C6 alkyl group, such as a C3 to C6 cycloalkyl group; a Cl to C6 alkoxy group; a Cl to C6 haloalkoxy group, such as -OCF3 or OCHF2; a haloalkyl group; and 23 r23,r r22'''^^ I R22 being selected from H, a halogen, a Cl to C6 alkyl group, a C3 to C6 cycloalkyl group, a Cl to C6 alkoxy group, a Cl to C6 haloalkyl group, and each R23 being independently selected from H, a halogen, a Cl to C6 linear or branched alkyl group, a Cl to C6 linear or branched aminoalkyl group, a Cl to C6 alkoxy group, a Cl to C6 haloalkoxy group, such as -OCF3 or OCHF2; and a Cl to C6 haloalkyl group. Optionally, each R1 and each R4 is independently absent or selected from H; a halogen, optionally Cl or F; a Cl to C3 alkyl group, optionally a methyl group; a Cl to C3 haloalkyl group, optionally a halomethyl group such as -CH2F, -CHF2, or -CF3; a haloethyl group, such as -CH2CF3; and a nitrile group. Further optionally, each R1 and each R4 is independently absent or selected from: H; Cl; F; a halomethyl group, such as CF3; and a nitrile group. Preferably, each R1 and each R4 is independently absent or selected from H and F. In such examples, each R4 may be H, and exactly one R1 may be F. R2 and R3 are each independently selected from H and a substituted or unsubstituted organic group. R2 may in particular be selected from H; a halogen, optionally F or Cl; a Cl to C3 alkyl group, optionally an isopropyl group or a cyclopropyl group; a Cl to C3 haloalkyl group, optionally -CH2F, -CHF2, -CF3, -CH2CF3, or -CH2CH2F; a Cl to C3 alcohol group, optionally -CH2CH2OH; a Cl to C3 alkoxy group, optionally a methoxy group, a methoxymethyl group, or methoxyethyl group; and a Cl to C3 aminoalkyl group. Most preferably, R2 is H. R3 is typically selected from H, a Cl to C3 alkyl group, and a Cl to C3 haloalkyl group. Most preferably, R3 is H. Head groups - aromatic examples 5 When each XD atom is C, and y is 1, ring D may be an aromatic ring. In such examples, the PARP1 inhibitor compound has a structure of: 10 The PARP1 inhibitor compound optionally has a structure of: In such examples, each R1 is preferably selected from H and F. More preferably, the PARP1 inhibitor compound may have a structure selected from: 15 The most preferred structures with aromatic D rings are: 5 Further examples of PARP1 inhibitor compounds with aromatic D rings include those having the following structures: Head groups - non-aromatic examples Alternatively, ring D may be non-aromatic. In such compounds, ring D may be a carbocycle 5 ora heterocycle. each R1 and each R4 being present. In particular, the compound may have a structure of: Alternatively, one XD atom may be O. In such examples, the PARP1 inhibitor compound may have a structure selected from: each R1 and each R4 being present. Of these, the following structures are preferred: The PARP1 inhibitor compound may in particular have a structure of: Alternatively, one XD atom may be N. In such examples, the PARP1 inhibitor compound may Of these, the following structure is preferred: Further examples of PARP1 inhibitor compounds include: The most preferred general structures for PARP1 inhibitor compounds with non-aromatic head groups are: O L group - general Group L of the PARP1 inhibitor compounds provided herein has a structure according to general formula: X1, X3, X4 and X5 are each independently selected from C and N; each X2 is independently selected from C, N, O, and S; n is 0,1, 2, 3, 4,or 5; m is 0,1, 2, 3, 4,or 5, with the proviso that n + m is in the range 2 to 5; 10 p is 1, 2 or 3; q is 1, 2 or 3, with the proviso that p + q is in the range 2 to 5; r is 0,1, 2, 3,4,or 5; s is 0,1, 2, 3,4, or 5, with the proviso that r + s is in the range 2 to 5; each R5A, R5B, and R5C is independently absent or selected from H and a substituted or 15 unsubstituted organic group; R6 is absent or selected from H and a substituted or unsubstituted organic group; and Q is a bond or a linking group having a structure selected from: wherein: t is 0,1, 2, 3, 4 or 5; u is 0,1, 2, 3, 4 and 5, with the proviso that t + u is in the range 0 to 6; and each R7 and R8 is independently selected from H and a substituted or unsubstituted organic group. One or more, and most preferably all, of the following provisos may apply: i) At least one X atom per ring is C. When ring A or ring B is 4-membered, that ring typically includes at most one heteroatom. When ring A or ring B is 5- or 6-membered, that ring typically includes at most three heteroatoms, optionally at most two heteroatoms. ii) Each of rings A, B, and C individually may comprise at most three heteroatoms. iii) The compound is not a quaternary ammonium compound. iv) The compound is free of O-O, S-S, and S-0 bonds. Each portion of group L is discussed in more detail below. Ring A Ring A of the PARP1 inhibitor compound has the general structure: 5A2 n is 0,1, 2, 3, 4,or 5; and m is 0,1, 2, 3,4,or 5, with the proviso that n + m is in the range 2 to 5. In other words, ring A may be a 4-, 5-, 6-, or 7-membered ring. Preferably, ring A is a 5-membered ring (n + m = 3) or a 6-membered ring (n + m = 4). Most preferably, ring A is a 5-membered ring (n + m = 3) Preferably, both n and m are at least 1. In other words, the atoms which connect ring A to rings D and B are preferably non-adjacent. X1 is bonded to ring E, and is selected from C and N. When X1 is N, R5A1 is absent. When X1 is C, R5A1 may be present or absent, and is preferably present. Each X2 is independently selected from C, N, O, and S. Preferably, each X2 is independently selected from C and N. Most preferably, each X2 is C. Each R5A group (i.e., R5A1, R5A2, R5A3) is independently absent or selected from H and a substituted or unsubstituted organic group. The number of R5A groups may be selected such that ring A is saturated, unsaturated and non-aromatic, or aromatic. Preferably, ring A is saturated. In most implementations, no more than two R5A groups are substituted or unsubstituted organic groups. Most typically, no more than one R5A group is a substituted or unsubstituted organic group. Generally, when an R5A group is present, that R5A group is preferably H. Ring A may be a bicyclic ring, in which two R5A groups are fused together. The bicyclic ring may be a bridged bicyclic ring. R5A3 is most typically H. It is preferable that, when present, each R5A is independently selected from H; a halogen, optionally F; a hydroxyl group; a carbonyl group; and a Cl to C3 alkyl group, optionally wherein a pair of R5A groups form a ring, further optionally wherein the ring bridges ring A. Particularly preferably: i) one pair of R5A groups forms -CH2- group bridging ring A, with each other R5A being H; or ii) each R5A is H. Ring A may be a 7-membered ring. For example, ring A may be a cycloheptane having a structure selected from: (to Ring E each R5A being present. Alternatively, ring A may be a 6-membered non-aromatic ring, such as a cyclohexane, cyclohexene, or tetrahydropyran. Ring A may for example have a structure selected from: each R5A being present. In accordance with another possibility, ring A may be a 5-membered non-aromatic ring, such as a cyclopentane, cyclopentene, or a tetra hydrofuran. Ring A may for example have a 5 structure selected from: each R5A being present. In other examples, ring A may be a 4-membered ring having a structure of: 5 each R5A and R5A3 being present. In accordance with still another possibility, ring A may be a bridged ring. Examples of suitable bridged ring structures include: each R5A being present. Ring A typically includes no more than one bridging group. In the three examples immediately above, no R5A groups are fused to form a further ring, and each 5 R5A group is preferably H. Examples of suitable structures for ring A include: where Qa represents a bond to ring E and Qb represents a bond to ring B. Ring A may have a structure of: 5 wherein: Qa represents a bond to ring E and Qb represents a bond to ring B; m is 1 or 2; n is 1 or 2; each R5A2 and R5A3 independently is absent or selected from H and a substituted or 10 unsubstituted organic group, preferably wherein R5A3 is H; and wherein: i) XI is C and R5A1 is selected from H and a substituted or unsubstituted organic group; or ii) XI is N and R5A1 is absent. Each R5A1, R5A2 and R5A3 may independently be absent or selected from H; a halogen, optionally F; a hydroxyl group; a carbonyl group; and a Cl to C3 alkyl group, optionally wherein a pair of R5A groups form a Cl to C3 alkyl group bridging ring A. Preferably, each R5A1, R5A2 and R5A3 is absent or H. Preferred A ring structures include: where Qa represents a bond to ring E and Qb represents a bond to ring B. Most preferably, ring A has a structure of: 15 Ring B Ring B of group L has a general structure of: B Each X2 is independently selected from C, N, O and S. X3 is selected from C and N. p is 1, 2 or 3; and q is 1, 2 or 3, with the proviso that p + q is in the range 2 to 5. In other words, ring B may be a 4-, 5-, 6- or 7-membered ring. Preferably, ring B is a 6-membered ring, and most preferably p and q are both equal to 2. Each R5B is independently absent or selected from H and a substituted or unsubstituted organic group. Preferably, each R5B is independently absent or H. Depending upon the number of R5B groups present, ring B may be saturated or unsaturated. Preferably, ring B is a saturated ring. Preferably, each X2 is C, and ring B has a structure of: X3 is preferably N. In such examples, ring B may have a structure of: 5B R (C)p Ring B may have a general structure selected from: r5B^' 5B R More specific examples of suitable ring B structures include: Most preferably, ring B has a structure of: Linker - Q group Ring B is coupled to ring C via a linker Q: Q may be a bond. In other words, atom X3 may be directly connected to ring C. 10 Alternatively, Qmay be a group selected from: t is a number selected from 0, 1, 2, 3, 4 and 5; and u is independently a number selected from 0,1, 2, 3, 4 and 5; with the proviso that t + u is a number selected from 0,1, 2, 3, 4, 5 and 6; and each R7 and R8 is independently selected from H and a substituted or unsubstituted organic group. Preferably, each R7 is independently selected from H; a halogen, optionally F; a Cl to C6 alkyl group; and a Cl to C6 haloalkyl group. When X3 of ring B is N, and Q is , t is typically at least one. When Qis: R8 may be selected from: H; a substituted or unsubstituted linear or branched Ci-Ce alkyl group (such as Me, Et, Pr, i-Pr, n-Bu, i-Bu, t-Bu, pentyl and hexyl); a substituted or unsubstituted linear or branched Ci-Ce alkyl-aryl group (such as -CH2Ph, -CH2(2,3 or 4)F-Ph, -CH2(2,3 or 4)CI-Ph, -CH2(2,3 or 4)Br-Ph, -CH2(2,3 or4)l-Ph, -CH2CH2Ph, -CH2CH2CH2Ph, -CH2CH2CH2CH2Ph, -CH2CH2CH2CH2CH2Ph, and -CH2CH2CH2CH2CH2CH2Ph); a substituted or unsubstituted linear or branched Ci-Ce halogenated alkyl group (such as -CH2F, -CF3, -CH2CH2F and -CH2CF3); a substituted or unsubstituted cyclic amine or amido group (such as pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, 2-keto-pyrrolidinyl, 3-keto-pyrrolidinyl, 2-keto-piperidinyl, 3-keto-piperidinyl, and 4-keto-piperidinyl); a substituted or unsubstituted cyclic C3-Cs alkyl group (such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl); a substituted or unsubstituted linear or branched C2-Ce alcohol group (such as -CH2CH2OH, -CH(CH3)CH2OH, -C(CH3)2OH, -CH2CH2CH2OH, -CH2CH2CH2CH2OH, -CH(CH3)CH2CH2OH, -CH(CH3)CH(CH3)OH, -CH(CH2CH3)CH2OH, -C(CH3)2CH2OH, -ch2ch2ch2ch2ch2oh, and -CH2CH2CH2CH2CH2CH2OH); a substituted or unsubstituted linear or branched C2-Ce carboxylic acid group (such as -CH2COOH, -CH2CH2COOH, -CH2CH2CH2COOH, -CH2CH2CH2CH2COOH, and -CH2CH2CH2CH2CH2COOH); a substituted or unsubstituted linear or branched carbonyl group (such as -(CO)Me, -(CO)Et, -(CO)Pr, -(CO)-i_Pr, -(CO)-n-Bu, -(CO)-i-Bu, -(CO)-t-Bu, -(CO)Ph, ~(CO)CH2Ph, -(CO)CH2OH, -(CO)CH2OCH3, -(CO)CH2NH2,-(CO)CH2NHMe, -(CO)CH2NMe2, -(CO)-cyclopropyl, -(CO)-l,3-epoxypropan-2-yl; -(CO)NH2, -(CO)NHMe , -(CO)NMe2, -(CO)NHEt, -(CO)NEt2, -(CO)-pyrollidine-N-yl, -(CO)-morpholine-N-yl, -(CO)-piperazine-N-yl, -(CO)-N-methyl-piperazine-N-yl, -(CO)NHCH2CH2OH, -(CO)NHCH2CH2OMe, -(CO)NHCH2CH2NH2, -(CO)NHCH2CH2NHMe, and -(CO)NHCH2CH2NMe2); a substituted or unsubstituted linear or branched Ci-Ce carboxylic acid ester group (such as -COOMe, -COOEt, -COOPr, -COO-i-Pr, -COO-n-Bu, -COO-i-Bu, -COO-t-Bu, -CH2COOMe, -CH2CH2COOMe, -CH2CH2CH2COOMe, and -CH2CH2CH2CH2COOMe); a substituted or unsubstituted linear or branched Ci-Ce amide group (such as -CO-NH2, -CO-NMeH, -CO-NMe2, -CO-NEtH, -CO-NEtMe, -CO-NEt2, -CO-NPrH, -CO-NPrMe, and -CO-NPrEt); a substituted or unsubstituted sulfonyl group (such as -SO2Me, -SO2Et, -SO2Pr, -SO2iPr, -SO2Ph, -SO2-(2,3 or 4)-F-Ph, -SO2-cyclopropyl, -SO2CH2CH2OCH3), -SO2NH2, -SO2NHMe, -SO2NMe2, -SO2NHEt, -SO2NEt2, -SO2-pyrrolidine-N-yl, -SO2-morpholine-N-yl, -SO2NHCH2OMe, and -SO2NHCH2CH2OMe); a substituted or unsubstituted aromatic group (such as Ph-, 2-F-Ph-, 3-F-Ph-, 4-F-Ph-, 2-CI-Ph-, 3-CI-Ph-, 4-CI-Ph-, 2-Br-Ph-, 3-Br-Ph-, 4-Br-Ph-, 2-l-Ph-, 3-l-Ph, 4-l-Ph-, 2,(3,4,5 or 6)-F2-Ph-, 2,(3,4,5 or 6)-CI2-Ph-, 2,(3,4,5 or 6)-Br2-Ph-, 2,(3,4,5 or 6)-l2-Ph-, 2,(3,4,5 or 6)-Me2-Ph-, 2,(3,4,5 or 6)-Et2-Ph-, 2,(3,4,5 or 6)-Pr2-Ph-, 2,(3,4,5 or 6)-Bu2-Ph-, 2,(3,4,5 or 6)-(CN)2-Ph-, 2,(3,4,5 or 6)-(NO2)2-Ph-, 2,(3,4,5 or 6)-(NH2)2-Ph-, 2,(3,4,5 or 6)-(MeO)2-Ph-, 2,(3,4,5 or 6)-(CF3)2-Ph-, 3,(4 or 5)-F2-Ph-, 3,(4 or 5)-CI2-Ph-, 3,(4 or 5)-Br2-Ph-, 3,(4 or 5)-l2-Ph-, 3,(4 or 5)-Me2-Ph-, 3,(4 or 5)-Et2-Ph-, 3,(4 or 5)-Pr2-Ph-, 3,(4 or 5)-Bu2-Ph-, 3,(4 or 5)-(CN)2-Ph-, 3,(4 or 5)-(NO2)2-Ph-, 3,(4 or 5)-(NH2)2-Ph-, 3,(4 or 5)-(MeO)2-Ph-, 3,(4 or 5)-(CF3)2-Ph-, 2-Me-Ph-, 3-Me-Ph-, 4-Me-Ph-, 2-Et-Ph-, 3-Et-Ph-, 4-Et-Ph-, 2-Pr-Ph-, 3-Pr-Ph-, 4-Pr-Ph-, 2-Bu-Ph-, 3-Bu-Ph-, 4-Bu-Ph-, 2-(CN)-Ph-, 3-(CN)-Ph-, 4-(CN)-Ph-, 2-(NO2)-Ph-, 3-(NO2)-Ph-, 4-(NO2)-Ph-, 2-(NH2)-Ph-, 3-(NH2)-Ph-, 4-(NH2)-Ph-, 2-MeO-Ph-, 3-MeO-Ph-, 4-MeO-Ph-, 2-(NH2-CO)-Ph-, 3-(NH2-CO)-Ph-, 4-(NH2-CO)-Ph-, 2-CF3-Ph-, 3-CF3-Ph-, 4-CF3-Ph-, 2-CF3O-Ph-, 3-CF3O-Ph-, and 4-CF3O-Ph-); and a substituted or unsubstituted heterocyclic group (such as pyrrole-2-yl, pyrrole-3-yl, pyrazole-3-yl, pyrazole-4-yl, pyrazole-5-yl, imidazole-2-yl, imidazole-4-yl, imidazole-5-yl, l,2,3-triazole-4-yl, l,2,3-triazole-5-yl, l,2,4-triazole-3-yl, l,2,4-triazole-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazine-3-yl, pyridazine-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrimidin-6-yl, pyrazine-2-yl, pyrrolidine-2-yl, pyrrolidine-3-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, 2-azapiperidine-3-yl, 2-azapiperidine-4-yl, 3-azapiperidine-2-yl, 3-azapiperidine-4-yl, 3-azapiperidine-5-yl, piperazine-2-yl, furan-2-yl, furan-3-yl, pyran-2-yl, pyran-3-yl, pyran-4-yl, 2-azapyran-3-yl, 2-azapyran-4-yl, 2-azapyran-5-yl, 2-azapyran-6-yl, 3-azapyran-2-yl, 3-azapyran-4-yl, 3-azapyran-5-yl, 3-azapyran-6-yl, 4-azapyran-2-yl, 4-azapyran-3-yl, 4-azapyran-5-yl, 4-azapyran-6-yl, tetra hydrofuran-2-yl, tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-4-yl, 2-aza-tetrahydrofuran-5-yl, 3-aza-tetrahydrofuran-2-yl, 3-aza-tetrahydrofuran-4-yl, 3-aza-tetrahydrofuran-5-yl, tetrahydropyran-2-yl, oxetan-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, 2-aza-tetrahydropyran-3-yl, 2-aza-tetrahydropyran-4-yl, 2-aza-tetrahydropyran-5-yl, 2-aza-tetrahydropyran-6-yl, 3-aza-tetrahydropyran-2-yl, 3-aza-tetrahydropyran-4-yl, 3-aza-tetrahydropyran-5-yl, 3-aza-tetrahydropyran-6-yl, morpholine-2-yl, morpholine-3-yl, thiophen-2-yl, thiophen-3-yl, isothiazole-3-yl, isothiazole-4-yl, isothiazole-5-yl, thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, thiopyran-2-yl, thiopyran-3-yl, thiopyran-4-yl, 2-azathiopyran-3-yl, 2-azathiopyran-4-yl, 2-azathiopyran-5-yl, 2-azathiopyran-6-yl, 3-azathiopyran-2-yl, 3-azathiopyran-4-yl, 3-azathiopyran-5-yl, 3-azathiopyran-6-yl, 4-azathiopyran-2-yl, 4-azathiopyran-3-yl, 4-azathiopyran-5-yl, 4-azathiopyran-6-yl, thiolane-2-yl, thiolane-3-yl, thiane-2-yl, thiane-3-yl, thiane-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, furazan-3-yl, (l,3,4-oxadiazol)-2-yl, (l,3,4-oxadiazol)-5-yl, (l,2,4-oxadiazol)-3-yl, (l,2,4-oxadiazol)-5-yl; and tetrazole-5-yl). In particular, R8 may be selected from H, a substituted or unsubstituted Ci-Ce alkyl group or a substituted or unsubstituted linear or branched Ci-Ce halogenated alkyl group. Preferably, Q is a bond or -CH2-. Most preferably, Q is a bond. Ring C Ring C of the PARP1 inhibitor compound has a structure of: X4 and X5 are each independently selected from C and N. Preferably, X4 is C and X5 is C. Rings B and C are not connected by N-N bonds. When Q is: tNu and u=0, X4 is C. When atom X3 of ring B is N and Q is a bond, X4 is C. Each X2 is independently selected from C, N, O, and S, with C and N being preferred. The X2 atoms are selected such that ring C is free of O-O, 0-S, and S-S bonds. Optionally, at least one X2 atom is C. Ring C is preferably a heterocycle. Optionally, one X2 atom is N, and each other X2 atom is C. Alternatively, each X2 atom is C. Each R5C is independently absent or selected from H and a substituted or unsubstituted organic group. Two R5C groups, or an R5C group and R6, may be fused such that ring C is a bridged ring system. Each R5C may be absent, H, or an organic group selected from a halogen, preferably F; a Cl to C3 alkyl group; a Cl to C3 haloalkyl group, optionally a fluoromethyl group such as CF2H or CF3; and a nitrile group. When an R5C group is present, that R5C group may in particular be selected from H and a halogen. The preferred halogen is F. Optionally, exactly one R5C is an organic group. That organic group is most preferably F. r is 0,1, 2, 3, 4,or 5 and s is 0,1, 2, 3, 4, or 5, with the proviso that r + s is in the range 2 to 5. In other words, ring C may be a 4-, 5-, 6-, or 7-membered ring. Optionally, ring C is a 5-membered ring (r + s = 3) or a 6-membered ring (r + s= 4), with 6-membered rings being preferred. Depending upon the chosen number of R5C groups, ring C may be a saturated ring, an unsaturated non-aromatic ring, or an aromatic ring. Preferably, ring C is an aromatic ring. Most preferably, ring C is a 6-membered aromatic ring. Ring C may be a 6-membered saturated ring, optionally having structure of: each R5C and R5C1 being independently selected from H and a substituted or unsubstituted organic group, preferably wherein R5C1 is H, more preferably wherein R5C1 and each R5C is H. Alternatively, ring C may be a 6-membered aromatic ring. For example, ring C may be an optionally-substituted phenyl group, optionally having a structure of: 5 each R5C being independently selected from H and a substituted or unsubstituted organic group, optionally wherein each R5C is H. In accordance with another possibility, ring C may be a pyridine group, optionally having a structure selected from: 10 each R5C being independently selected from H and a substituted or unsubstituted organic group, optionally wherein each R5C is H. Alternatively, ring C may be a diazine group, optionally having a structure selected from: each R5C being independently selected from H and a substituted or unsubstituted organic 5 group, optionally wherein each R5C is H. Compounds wherein ring C is a 5-membered aromatic ring are also contemplated. For example, ring C may be an imidazole group, optionally an imidazole group having a 10 structure selected from: each R5C being independently selected from H and a substituted or unsubstituted organic group, optionally wherein each R5C is H. 15 Alternatively, ring C may be a thiophene group, optionally having a structure selected from: each R5C being independently selected from H and a substituted or unsubstituted organic group, optionally wherein each R5C is H. In accordance with another possibility, ring C may be thiazole group, optionally having a structure selected from: 5 each R5C being independently selected from H and a substituted or unsubstituted organic group, optionally wherein each R5C is H. In still other examples, ring C may be a triazole, optionally having a structure of: 10 R5C being selected from H and a substituted or unsubstituted organic group, optionally wherein R5C is H. Examples of suitable ring C structures include: CN Ring C may have a structure of: Co wherein: 5 XCo and XCm are each selected from C and N, preferably wherein exactly one of XCo and XCm is N; when XCo is C, RCo is H ora halogen, optionally F; when XCo is N, RCo is absent; when XCm is C, RCm is H or a halogen, optionally F; and 10 when XCm is N, RCm is absent. When present, RCo is preferably H or F. When present, RCm is preferably H. Most preferably, ring C has a structure selected from: 5 Terminal substituent R6 Ring C bears a substituent R6, which is selected from H and a substituted or unsubstituted organic group. 10 R6 may in particular be selected from H, -F, -Cl, -Br, -I, -CN, -CONR51R51, -NR51COR52, -SO2NR51R51, -NR51SO2R52, -O-CR52R52R52, -CR52R52NR51R51, and any of the following structures: R51 and R52 are each independently selected from H and a substituted or unsubstituted organic group. Optionally, R51 and R52 are each independently selected from H, a halogen, optionally-deuterated Cl to C3 alkyl, and Cl to C3 haloalkyl. Optionally, R6 is selected from -F, -Cl, -CN, -CONH2, -CONHMe (optionally -CONHCD3), -CONHEt, -CONMe2, -CONHCOMe, -CONHCH2-CH2OMe, -CONH-CH2-CH2F, -CONH-CH2-CF3, -CONH-CH2-CHF2, -OCHF2, -NHCOMe, -NHSO2Me, -SO2NHMe, -CONHSO2Me, Particularly preferably, R6 is selected from: i) CONHMe; ia) CONHCD3; ii) Cl; and iii) CN. Where a compound is depicted with an R6 group selected from i) to iii) as defined immediately above, replacement of the R6 group with any other one of groups i) to iii) is explicitly contemplated. Example L groups Group L of the PARP1 inhibitor compound may in particular be selected from: 5 Rings E and B of the PARP1 inhibitor compound may be in a cis configuration with respect to ring A. In such compounds, group L may be selected from: Alternatively, rings E and B may be in a trans configuration with respect to ring A. In such compounds, group L may be selected from: Example Compounds Provided herein are PARP1 inhibitor compounds having a structure of: where each Z independently represents -CH2- or a heteroatom-containing fragment selected from -O- and -N(RD)-, with the proviso that no more than one Z is a heteroatomcontaining fragment; wherein RD is H or a Cl to C3 alkyl group; XC1 and XC2 are each independently selected from C and N; when XC1 is N, R5C1 is absent; when XC1 is C, R5C1 is selected from H and a halogen, preferably F; when XC2 is N, R5C2 is absent; when XC2 is C, R5C2 is selected from H and a halogen, preferably F; R6 is selected from -CONHMe, -Cl, and -CN. When present, RD is preferably a methyl group. When present, R5C1 is preferably H or F. When present, R5C2 is preferably H or F. XC2 is preferably N. More preferably, XC1 is C and XC2 is N. R6 is preferably -CONHMe, e.g. -CONHCD3. The compound may have a cis configuration: The compound may be selected from the following: 13trans Also provided herein are PARP1 inhibitor compounds according to general formula: 5 RD1 and RD2 are each independently selected from H and F; XC1 and XC2 are each independently selected from C and N; when XC1 is N, R5C1 is absent; when XC1 is C, R5C1 is selected from H and a halogen, preferably F; when XC2 is N, RC2 is absent; when XC2 is C, R5C2 is selected from H and a halogen, preferably F; R6 is selected from -CONHMe, -Cl, and -CN. 5 Preferably, exactly one of RD1 and RD2 is F. Preferably, exactly one of XC1 and XC2 is N. For instance, XC1 may be C and XC2 may be N. Alternatively, XC2 may be C and XC1 may be N; in such examples, R5C2 is preferably H. 10 The compound may have a cis configuration: DI The PARP1 inhibitor compound may have a structure selected from: lOtrans Medical Uses The compounds described herein may be for use in medicine. In the context of the present 5 invention, the medicinal use is not especially limited, provided that it is a use which is facilitated by the PARP1 inhibitory effect of the compound. Thus, the compounds of the invention may be for use in any disease, condition or disorder that may be prevented, ameliorated or treated using a PARP1 inhibitor. The PARP1 inhibitor compounds provided herein may be selective for PARP1 over PARP2. As such, the PARP1 inhibitor compounds may have reduced toxicity. PARP2 inhibition is believed to be a major driver of haematological toxicities such as anaemia, neutropenia and thrombocytopenia. The PARP1 inhibitor compound may be for use in treating a cancer. The nature of the cancer is not especially limited, provided that the cancer is one which may be treated, prevented or ameliorated by using a PARP1 inhibitor. The cancer may comprise a solid or liquid tumour. For example, the cancer may be selected from: a cancer of the eye, brain (such as gliomas, glioblastomas, medulloblastomas, craniopharyngioma, ependymoma, and astrocytoma), spinal cord, kidney, mouth, lip, throat, oral cavity, nasal cavity, small intestine, colon, parathyroid gland, gall bladder, head and neck, breast, bone, bile duct, cervix, heart, hypopharyngeal gland, lung, bronchus, liver, skin, ureter, urethra, testicles, vagina, anus, laryngeal gland, ovary, thyroid, oesophagus, nasopharyngeal gland, pituitary gland, salivary gland, prostate, pancreas, adrenal glands; an endometrial cancer, oral cancer, melanoma, neuroblastoma, gastric cancer, an angiomatosis, a hemangioblastoma, a pheochromocytoma, a pancreatic cyst, a renal cell carcinoma, Wilms' tumour, squamous cell carcinoma, sarcoma, osteosarcoma, Kaposi sarcoma, rhabdomyosarcoma, hepatocellular carcinoma, PTEN Hamartoma-Tumor Syndromes (PHTS) (such as Lhermitte-Duclos disease, Cowden syndrome, Proteus syndrome, and Proteus-like syndrome), leukaemias and lymphomas (such as acute lymphoblastic leukaemia, chronic lymphocytic leukaemia, acute myelogenous leukaemia, chronic myelogenous leukaemia, hairy cell leukaemia, T-cell prolymphocytic leukaemia (T-PLL), large granular lymphocytic leukaemia, adult T-cell leukaemia juvenile myelomonocytic leukaemia, Hodgkin lymphoma, non-Hodgkin lymphoma, mantle lymphoma, follicular lymphoma, primary effusion lymphoma, AIDS-related lymphoma, diffuse B cell lymphoma, Burkitt lymphoma, cutaneous T-cell lymphoma, nasopharyngeal and gastrointestinal cancers. For instance, the cancer may be a cancer of the brain or spinal cord. In addition, the compounds described herein may be of use in cancers where Epstein Barr Virus, EBV, plays a contributing role such as Burkitt's lymphoma, Hodgkin's lymphoma, nasopharyngeal and gastrointestinal cancers. The compounds described herein may be provided for use in for treating a cancer which is deficient in one or more DNA damage response repair pathways, in particular in Homologous Recombination ("HR") dependent DNA Double Strand Break ("DSB") DNA repair activity. Components of HR dependent DNA DSB repair pathways and other DNA damage response pathways include but are not limited to the following proteins: ATM, ATR, ERCC1, XRCC1, XRCC2, XRCC3, RAD51, RAD51L1, RAD51C, RAD51D, RAD51L3, DMC1, RAD52, RAD54L, RAD54B, RAD50, MRE11A, NBS1, BRCA1, BRCA2, FANCP (SLX4), FEN1, PALB2, PBRM1, SMARCA4, ARID1A, ARID1B, FANCD2, BLM. Other components involved in HR dependent DNA DSB repair include regulatory factors such as ESMY (Hughes-Davies, L. et al. Cell. 2003; 115: 523-535). A cancer which is deficient in HR-dependent DNA DSB repair typically becomes dependent on alternative DSB pathway repair mechanisms. Such cancers include but are not limited to cancers of the ovary, prostate, breast, lung, gastrointestine, blood and pancreas. The cancer cells may have a BRCA1 and / or BRCA2 deficient phenotype, i.e. the cancer cells may be deficient in BRCA1 and / or 2 function. The deficiency may arise by means of mutation, polymorphism or epigenetic silencing in the encoding nucleic acids or by means of mutation, polymorphism, amplification in a gene encoding a regulatory factor, e.g. the ESMY gene which encodes a BRCA2 regulatory factor (Hughes-Davies, L. et al. Cell. 2003; 115: 523-535). Amplification of the ESMY gene is associated with breast and ovarian cancer. Carriers of mutations in the tumour suppressor BRCA1 and / or BRCA2 genes are known to have an elevated risk of developing certain cancers including ovarian, prostate and breast. Wild-type alleles of BRCA1 and / or BRCA2 are frequently lost in tumours of heterozygous carriers (Jasin, M. et al. Oncogene. 2002; 21: 8981-93) and their detection, as a means of patient selection, is well known in the art (Radice, PJ. et al. Exp. Clin. Cancer. Res. 2002; 21: 9-12; Chappnis, PO and Foulkes WO. Cancer Treat Res. 2002; 107: 29-59). The compounds provided herein may be administered to a patient who is undergoing radiotherapy and / or chemotherapy using a further agent for treating cancer. For example, the PARP1 inhibitor compound may be administered in conjunction with a further agent for treating cancer. The further agent for treating cancer may be selected from: anti-microtubule agents, platinum coordination complexes, alkylating agents, antibiotic agents, topoisomerase I inhibitors, topoisomerase II inhibitors, antimetabolites, senolytic agents, hormones and hormone analogues, signal transduction pathway inhibitors, other DNA damage repair pathway inhibitors, non-receptor tyrosine kinase angiogenesis inhibitors, antibody-drug conjugates, immunotherapeutic agents, hormone deprivation therapy, proapoptotic agents, radioligand therapies, cell cycle signalling inhibitors, and anti-angiogenic agents. In particular, the further agent may comprise an immunotherapeutic agent selected from: an anti-tumour vaccine; an oncolytic virus; an immune stimulatory antibody such as anti-CTLA4, anti-PDl, anti-PDL-1, anti-OX40, anti-41BB, anti-CD27, anti-CD40, anti-LAG3, anti-TIM3, and anti-GITR; a pattern recognition receptor agonist such as a STING, TLR-9 or RIG-1 Helicase agonist; an IDO orTDO inhibitor; a novel adjuvant; a peptide; a cytokine; a chimeric antigen receptor T cell therapy (CAR-T); a small molecule immune modulator; and a tumour microenvironment modulator. Pharmaceutical Compositions Another aspect provides a pharmaceutical composition comprising a PARP1 inhibitor compound as defined herein. Typically, the composition includes a pharmaceutically acceptable additive and / or excipient. In the pharmaceutical composition, the PARP1 inhibitor compound as defined above may be present in the form described above, but may alternatively be in a form suitable for improving bioavailability, solubility, and / or activity, and / or may be in a form suitable for improving formulation. Thus, the compound may be in the form of a pharmaceutically acceptable salt, hydrate, acid, ester, or other alternative suitable form. Typically, the composition is for use in medicine, e.g. for use in treating a disease, condition or disorder as defined above. For example, the pharmaceutical composition may be for use in treating a cancer. The composition may further comprise a further agent for treating cancer. The further agent for treating cancer is not especially limited, provided that it affords some utility for cancer treatment. The further agent for treating cancer may comprise one or more chemotherapeutic agents such as anti-microtubule agents, platinum coordination complexes, alkylating agents, antibiotic agents, topoisomerase I inhibitors, topoisomerase II inhibitors, antimetabolites, senolytic agents, hormones and hormone analogues, signal transduction pathway inhibitors, other DNA damage repair pathway inhibitors, non-receptor tyrosine kinase angiogenesis inhibitors, antibody-drug conjugates, immunotherapeutic agents, hormone-deprivation therapies, proapoptotic agents, radioligand therapies, anti-angiogenic agents, and cell cycle signalling inhibitors. In particular, the further agent for treating cancer may comprise an immunotherapeutic agent selected from: an anti-tumour vaccine; an oncolytic virus; an immune stimulatory antibody such as anti-CTLA4, anti-PDl, anti-PDL-1, anti-OX40, anti-41BB, anti-CD27, anti-CD40, anti-LAG3, anti-TIM3, and anti-GITR; a pattern recognition receptor agonist such as a STING, TLR-9 or RIG-1 Helicase agonist; an IDO or TDO inhibitor; a novel adjuvant; a peptide; a cytokine; a chimeric antigen receptor T cell therapy (CAR-T); a small molecule immune modulator; and a tumour microenvironment modulator. Kits Another aspect provides a pharmaceutical kit for treating a cancer. The pharmaceutical kit comprises a PARP1 inhibitor compound as defined herein, and a further agent for treating cancer. The compound and the further agent are suitable for administration simultaneously, sequentially or separately. The further agent for treating cancer may be any of the further agents for treating cancer identified above in the discussion of the pharmaceutical composition. In particular, the further agent for treating cancer may comprise one or more chemotherapeutic agents selected from: anti-microtubule agents, platinum coordination complexes, alkylating agents, antibiotic agents, topoisomerase I inhibitors, topoisomerase II inhibitors, antimetabolites, senolytic agents, hormones and hormone analogues, signal transduction pathway inhibitors, other DNA damage repair pathway inhibitors, non-receptor tyrosine kinase angiogenesis inhibitors, antibody-drug conjugates, hormone-deprivation therapies, radioligand therapies, antiangiogenic agents, immunotherapeutic agents (such as selected from an anti-tumour vaccine, an oncolytic virus, an immune stimulatory antibody such as anti-CTLA4, anti-PDl, anti-PDL-1, anti-OX40, anti-41BB, anti-CD27, anti-CD40, anti-LAG3, anti-TIM3, and anti-GITR, a pattern recognition receptor agonist such as a STING, TLR-9 or RIG-1 Helicase agonist, an IDO orTDO inhibitor, a novel adjuvant, a peptide, a cytokine, a chimeric antigen receptor T cell therapy (CAR-T), a small molecule immune modulator, tumour microenvironment modulators), proapoptotic agents and cell cycle signalling inhibitors. Methods of Treatment Another aspect of the invention provides a method of treating a disease and / or a condition and / or a disorder, which method comprises administering to a patient (or subject) a PARP1 inhibitor compound, or a composition, or a kit as defined herein. The method is typically a method for treating any disease condition or disorder mentioned herein. In typical embodiments, the method is a method for treating a cancer. The patient may be any animal, preferably a mammal. For example, the patient may be a human, canine, equine or feline; and is preferably a human. The method may comprise administering to the patient (or subject) a compound or a composition as defined above and a further agent for treating cancer as defined above. The compound or composition and the further agent may be administered simultaneously, sequentially or separately, depending upon the agents and patients involved, and the disease to be treated (e.g., the type of cancer to be treated). The patient may be undergoing treatment using ionising radiation. Methods of synthesising PARP1 inhibitor compounds Also provided are methods for synthesising the PARP1 inhibitor compounds as defined herein. In general, the method comprises conducting a reaction between: (i) a first reactant comprising rings D and E and bearing a first portion of group L, and (ii) a second reactant comprising a remainder of group L, to form the PARP1 inhibitor compound. The skilled person may select reaction conditions with reference to known synthesis techniques depending on the appropriate starting materials. The method may comprise one or more additional steps. Exemplary synthesis methodology is shown in the Examples hereinbelow. In one example method, the first reactant comprises rings D, E and ring A, and the second reactant comprises a ring B precursor bearing a reactive group, which method comprises joining ring A to the ring B precursor. In this method, the reactive group of the ring B precursor may comprise a carbonyl group, an alkyl halide, or an alkyl sulfonate. The reaction may comprise alkylation, reductive amination, or amide formation so as to form group L. In another example method, the first reactant comprises rings D, E, ring A, and ring B, and the second reactant comprises a ring C derivative bearing a leaving group such as a halide or sulfonate. In this method, the reaction may comprise a nucleophilic substitution reaction, such as a nucleophilic aromatic substitution reaction, so as to form group L. The PARP1 inhibitor compound may be obtained in the form of a mixture of two or more structural isomers. The method may further comprise separating the structural isomers. For example, the method may further comprise comprising separating structural isomers of the PARP1 inhibitor compound using chiral supercritical fluid chromatography ("SFC") and / or chiral high-performance liquid chromatography ("HPLC"). When the PARP1 inhibitor compound is diastereomeric, separation may proceed in two stages. In a first stage, two pairs of stereoisomers may be isolated by HPLC. In a second stage, individual stereoisomers may be isolated from the pairs of stereoisomers by SFC. Examples Example 1: synthesis of compound 5cis-a, 5cis-b, 5trans-a, 5trans-b 1003 1005 5 1006 Preparation of 8-fluoro-2-(4-methoxybenzyl)-3-(3-oxocyclopent-l-en-l-yl)isoquinolin-l(2H)-one (1003) A suspension of 3-chloro-8-fluoro-2-(4-methoxybenzyl)isoquinolin-l(2H)-one 1001 (1800 mg, 5.6650 mmol), 3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)cyclopent-2-en-l-one 1002 (1178 mg, 5.6650 mmol), Na2CO3 (1201 mg, 11.3300 mmol) and Pd(dppf)CI2 (462 mg, 0.5665 mmol) in dioxane (100 mL) was heated at 100 °C for 8 h under N2. After cooling to rt, the reaction mixture was poured into ice water and then extracted with EtOAc (200 mix 3). The combined organic layers were washed with water, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by flash silica chromatography (eluting with EtOAc / PE, 0 to 15 %) to give 8-fluoro-2-(4-methoxybenzyl)-3-(3-oxocyclopent-l-en-l-yl)isoquinolin-l(2H)-one 1003 (800 mg, 80 % purity, 31 % yield) as a yellow oil. LCMS (ESI) calcd for C22Hi8FNO3 [M + H] + m / z 364.13, found 364.00. Preparation of 5-(4-(3-(8-fluoro-2-(4-methoxybenzyl)-l-oxo-l,2-dihydroisoquinolin-3-yljcyclopen t-2-en-l -yl)piperazin-l -yl)-N-methylpicolin amide (1005) To a solution of 8-fluoro-2-(4-methoxybenzyl)-3-(3-oxocyclopent-l-en-l-yl)isoquinolin-l(2H)-one 1003 (300 mg, 0.8256 mmol) in MeOH (6 mL) were added N-methyl-5-(piperazin-l-yl)picolinamide 1004 (218 mg, 0.9907 mmol), NaBH(OAc)3 (875 mg, 4.1280 mmol) and NaBH3CN (259 mg, 4.1280 mmol) successively. The reaction mixture was stirred at 60 °C for 48 h. The reaction mixture was quenched with water and concentrated under reduced pressure. The residue was purified by flash column chromatography (eluting with DCM / MeOH = 100:0 to 90:10) to afford 5-(4-(3-(8-fluoro-2-(4-methoxybenzyl)-l-oxo-l,2- dihydroisoquinolin-3-yl)cyclopent-2-en-l-yl)piperazin-l-yl)-N-methylpicolinamide 1005 (220 mg, 90 % purity, 42 % yield) as colorless oil. LCMS (ESI) calcd for C33H34FN5O3 [M + H] + m / z 568.26, found 568.30. Preparation of 5-(4-(3-(8-fluoro-2-(4-methoxybenzyl)-l-oxo-l,2-dihydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)-N-methylpicolinamide (1006) A solution of 5-(4-(3-(8-fluoro-2-(4-methoxybenzyl)-l-oxo-l,2-dihydroisoquinolin-3-yl)cyclopent-2-en-l-yl)piperazin-l-yl)-N-methylpicolinamide 1005 (200 mg, 0.3523 mmol) and Pd(OH)2 / C (99 mg, 0.7046 mmol) in MeOH (5 mL) was stirred at 50 °C for 48 h under H2 atmosphere. The resulting solution was filtered through diatomaceous earth and the filter cake was washed with DCM (10 mL). The filtrate was concentrated under reduced pressure to give 5-(4-(3-(8-fluoro-2-(4-methoxybenzyl)-l-oxo-l,2-dihydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)-N-methylpicolinamide 1006 (180 mg, 85 % purity, 76 % yield) as colorless oil. LCMS (ESI) calcd for C33H36FN5O3 [M + H] + m / z 570.28, found 570.35. Preparation of 5-(4-(3-(8-fluoro-l-oxo-l,2-dihydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)-N-methylpicolinamide (5cis-a, 5cis-b, 5trans-a, and 5trans-b) A solution of 5-(4-(3-(8-fluoro-2-(4-methoxybenzyl)-l-oxo-l,2-dihydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)-N-methylpicolinamide 1006 (180 mg, 0.3160 mmol) in TFA (3 mL) and TfOH (0.3 mL) was stirred at 100 °C for 10 min. The reaction solution was cooled to rt and the reaction solution was adjusted to pH 8 with aq. NaHCOs and extracted with EtOAc (100 mL x 2). The combined organic layers were concentrated under reduced pressure and purified by prep-HPLC (column : Gemini - C18 150 x 21.2 mm, 5 pm; mobile phase: ACN - H2O (0.05 % NH3); gradient : 25 - 70) to obtain 5-(4-(3-(8-fluoro-l-oxo-l,2-dihydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)-N-methylpicolinamide 5cis-a / 5cis-b racemic mixture (27.6 mg, 95 % purity, 18 % yield) as a white solid and 5-(4-(3-(8-fluoro-l-oxo-l,2-dihydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)-N-methylpicolinamide 5trans-a / 5trans-b racemic mixture (7.5 mg, 98 % purity, 5 % yield) as a white solid. 5cis-a / 5cis-b racemic mixture XH NMR (400 MHz, DMSO-de, ppm) 6: 11.63 (s, 1 H), 8.44-8.36 (m, 1 H), 8.29 (d, J = 2.8 Hz, 1 H), 7.84 (d, J = 8.8 Hz, 1 H), 7.64-7.57 (m, 1 H), 7.42 (dd, J = 8.8, 2.8 Hz, 1 H), 7.36 (d, J = 7.6 Hz, 1 H), 7.11-7.04 (m, 1 H), 6.45 (s, 1 H), 3.52-3.35 (m, 4 H), 3.12-2.99 (m, 1 H), 2.79 (d, J = 4.8 Hz, 3 H), 2.72-2.61 (m, 5 H), 2.2-2.05 (m, 2 H), 1.89-1.63 (m, 4 H). NOE experiments suggested a cis stereochemistry for this pair of enantiomers. LCMS (ESI) calcd for C25H28FN5O2 [M + H]+ m / z 450.22, found 450.40. 5trans-a / 5trans-b racemic mixture 2H NMR (400 MHz, DMSO-d6, ppm) 6: 11.17 (s, 1 H), 8.43-8.34 (m, 1 H), 8.27 (d, J = 2.8 Hz, 1 H), 7.83 (d, J = 8.8 Hz, 1 H), 7.65-7.57 (m, 1 H), 7.43-7.34 (m, 2 H), 7.13-7.05 (m, 1 H), 6.42 (s, 5 1 H), 3.36-3.32 (m, 4 H), 3.10-2.96 (m, 1 H), 2.90-2.81 (m, 1 H), 2.78 (d, J = 4.8 Hz, 3 H), 2.65- 2.54 (m, 4 H), 2.13-1.94 (m, 3 H), 1.92-1.80 (m, 1 H), 1.77-1.64 (m, 1 H), 1.61-1.48 (m, 1 H). NOE experiments suggested a trans stereochemistry for this pair of enantiomers. 10 LCMS (ESI) calcd for C25H28FN5O2 [M + H]+ m / z 450.22, found 450.25. Example 2: synthesis of2cis-a, 2cis-b, 2trans-a, 2trans-b yi O F 1 MeONa p 1 MeOH, 60 °C Ol 1102 1101 1002 -------------------* RuPhos Pd G3, RuPhos Cl Na2CO3, Dioxane / H2O, 90 °C 1105 TMSI ACN, 50 °C O Fy^pNH Preparation of 3-chloro-7-fluoro-l -methoxyisoquinoline (1102) To a solution of l,3-dichloro-7-fluoroisoquinoline 1101 (1.0 g, 4.65 mmol) in MeOH (15 mL) was added MeONa (251 mg, 4.65 mmol) under N2. The reaction mixture was stirred at 60 °C for 16 h. The reaction solution was cooled to rt, quenched with water, and extracted with EtOAc (100 mL x 4). The combined organic layer was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by flash chromatography (eluting with PE / EtOAc = 100: 0 to 50: 50) to give 3-chloro-7-fluoro-l-methoxyisoquinoline 1102 (900 mg, 80 % purity, 73 % yield) as a white solid. LCMS (ESI) calcd for C10H7CIFNO [M + H] + m / z 212.02, found 212.10. Preparation of 3-(7-fluoro-l-methoxyisoquinolin-3-yl)cyclopent-2-en-l-one (1103) To a solution of 3-chloro-7-fluoro-l-methoxyisoquinoline 1102 (900 mg, 4.25 mmol), 3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)cyclopent-2-en-l-one 1002 (1.06 g, 5.11 mmol) and RuPhos Pd G3 (357 mg, 0.43 mmol) in dioxane / H2O = 10 : 1 (15 mL) was added Na2CO3 (901 mg, 8.50 mmol) under N2. The reaction mixture was stirred at 90 °C for 2 h. The reaction solution was cooled to rt, quenched with water, and extracted with EtOAc (100 mL x 4). The combined organic layer was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by flash chromatography (eluting with PE / EtOAc = 100: 0 to 50: 50) to give 3-(7-fluoro-l-methoxyisoquinolin-3-yl)cyclopent-2-en-l-one 1103 (800 mg, 90 % purity, 66 % yield) as a white solid. LCMS (ESI) calcd for C15H12FNO2 [M + H] + m / z 258.09, found 258.10. Preparation of 5-(4-(3-(7-fluoro-l-methoxyisoquinolin-3-yl)cyclopent-2-en-l-yl)piperazin-l-yl)-N-methylpicolinamide (1104) To a solution of 3-(7-fluoro-l-methoxyisoquinolin-3-yl)cyclopent-2-en-l-one 1103 (460 mg, 1.79 mmol) in MeOH (20 mL) was added N-methyl-5-(piperazin-l-yl)picolinamide hydrochloride 1004 (1.37 g, 5.40 mmol) and 2 drops of AcOH, then NaBHsCN was added (1.12 g, 17.9 mmol). The reaction mixture was added to stir at 60 °C for 48 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by flash chromatography (eluting with DCM / MeOH = 100 : 0 to 90: 10) to give 5-(4-(3-(7-fluoro-l- methoxyisoquinolin-3-yl)cyclopent-2-en-l-yl)piperazin-l-yl)-N-meth-ylpicolinamide 1104 (530 mg, 70 % purity, 44 % yield) as a white solid. LCMS (ESI) calcd for C26H28FN5O2 [M + H]+ m / z 462.22, found 462.20. Preparation of 5-(4-(3-(7-fluoro-l-methoxyisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)-N-methylpicolinamide (1105) To a solution of 5-(4-(3-(7-fluoro-l-methoxyisoquinolin-3-yl)cyclopent-2-en-l-yl)piperazin-l-yl)-N-meth-ylpicolinamide 1104 (530 mg, 1.14 mmol) in MeOH (20 mL) was added Pd(OH)2 / C (160 mg) under H2. The reaction mixture was stirred at 50 °C for 4 h. The resulting solution was filtered through a celite pad, and the filtrate was concentrated under reduced pressure to give 5-(4-(3-(7-fluoro-l-methoxyisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)-N-methylpicolinamide 1105 (320 mg, 70 % purity, 42 % yield) as white solid. LCMS (ESI) calcd for C26H3oFN502 [M + H]+ m / z 464.24, found 464.30. Preparation of 5-(4-(3-(7-fluoro-l-oxo-l,2-dihydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)-N-methylpicolinamide (2cis-a, 2cis-b, 2trans-a, 2trans-b) To a solution of 5-(4-(3-(7-fluoro-l-methoxyisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)-N-methylpicolinamide 1105 (320 mg, 0.69 mmol) in ACN (20 mL) was added TMSI (414 mg, 2.07 mmol). The reaction mixture stirred at 50 °C for 3 h. the mixture was concentrated under reduced pressure. The residue was purified by prep-HPLC (columns: Gemini 5 pm C18 150 x 21.2 mm, mobile phase: ACN - H2O (0.05 % NH3), gradient: 30 - 65) to give 5-(4-(3-(7-fluoro-l-oxo-l,2-dihydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)-N-methylpicolinamide 2cis-a, 2cis-b racemic mixture (cis, 38 mg, 95 % purity, 10 % yield) and 5-(4-(3-(7-fluoro-l-oxo-l,2-dihydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)-N-methylpicolinamide 2trans-a, 2trans-b racemic mixture (trans, 68 mg, 98 % purity, 21 % yield) as white solid. Preparation of 5-(4-(3-(7-fluoro-l-oxo-l,2-dihydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)-N-methylpicolinamide (2cis-a and 2cis-b) 5-(4-(3-(7-fluoro-l-oxo-l,2-dihydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)-N-methylpicolinamide 2cis-a, 2cis-b racemic mixture (38 mg, 0.08 mmol) was separated by SFC (Column: DAICEL IH 20 mm I.D. x 250 mm, 5 pm; Mobile phase: CO2 / MeOH [0.1% NH3 (7 M Solution in MeOH)] = 60 / 40) and concentrated under reduced pressure to afford the first fraction as 2cis-a (8.6 mg, 95.49 % purity, ee%: 100, white solid) and the second fraction as 2cis-b (10.7 mg, 97.15 % purity, ee%: 100, white solid). 2cis-a TH NMR (400 MHz, DMSO-c / 6, ppm) 6: 11.80 (s, 1 H), 8.44-8.35 (m, 1 H), 8.29 (d, J = 2.4 Hz, 1 H), 7.85 (d, J = 8.8 Hz, 1 H), 7.75 (dd, J = 9.2, 2.4 Hz, 1 H), 7.71-7.63 (m, 1 H), 7.59-7.51 (m, 1 H), 7.42 (dd, J = 8.8, 2.8 Hz, 1 H), 6.50 (s, 1 H), 3.53-3.35 (m, 4 H), 3.14-3.01 (m, 1 H), 2.79 (d, J = 4.8 Hz, 3 H), 2.75-2.69 (m, 1 H), 2.69-2.60 (m, 4 H), 2.23-2.06 (m, 2 H), 1.93-1.83 (m, 1 H), 1.82-1.72 (m, 2 H), 1.71-1.59 (m, 1 H). NOE experiments suggested cis stereochemistry for this compound. LCMS (ESI) calcd for C25H28FN5O2 [M + H]+ m / z 450.22, found 450.40. 2cis-b 2H NMR (400 MHz, DMSO-d6, ppm) 6: 11.80 (s, 1 H), 8.48-8.35 (m, 1 H), 8.29 (d, J = 2.4 Hz, 1 H), 7.85 (d, J = 8.8 Hz, 1 H), 7.75 (dd, J = 9.2, 2.4 Hz, 1 H), 7.70-7.63 (m, 1 H), 7.59-7.50 (m, 1 H), 7.42 (dd, J = 8.8, 2.8 Hz, 1 H), 6.50 (s, 1 H), 3.52-3.35 (m, 4 H), 3.14-3.00 (m, 1 H), 2.79 (d, J = 4.8 Hz, 3 H), 2.75-2.69 (m, 1 H), 2.69-2.61 (m, 4 H), 2.23-2.05 (m, 2 H), 1.94-1.82 (m, 1 H), 1.81-1.72 (m, 2 H), 1.71-1.58 (m, 1 H). NOE experiments suggested cis stereochemistry for this compound. LCMS (ESI) calcd for C25H28FN5O2 [M + H] + m / z 450.22, found 450.40. Preparation of 5-(4-(3-(7-fluoro-l-oxo-l,2-dihydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)-N-methylpicolinamide (2trans-a and 2trans-b) 5-(4-(3-(7-fluoro-l-oxo-l,2-dihydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)-N-methylpicolinamide 2trans-a, 2trans-b racemic mixture (68 mg, 0.15 mmol) was separated by SFC (Column: DAICEL IH 20 mm I.D. x 250 mmL, 5 pm; Mobile phase: CO2 / MeOH [0.1 % NH3 (7 M Solution in MeOH)] = 60 / 40) and concentrated under reduced pressure to afford the first fraction as 2trans-a (18.0 mg, 98.04 % purity, ee%: 100, white solid) and the second fraction as 2trans-b (16.0 mg, 97.86 % purity, ee%: 100, white solid). 2trans-a XH NMR (400 MHz, DMSO-d6, ppm) 6: 11.32 (s, 1 H), 8.43-8.33 (m, 1 H), 8.27 (d, J = 2.8 Hz, 1 H), 7.86-7.80 (m, 1 H), 7.77 (dd, J = 9.6, 2.8 Hz, 1 H), 7.72-7.65 (m, 1 H), 7.59-7.50 (m, 1 H), 7.39 (dd, J = 8.8, 2.8 Hz, 1 H), 6.47 (s, 1 H), 3.35-3.32 (m, 4 H), 3.11-2.99 (m, 1 H), 2.90-2.80 (m, 1 H), 2.78 (d, J = 4.8 Hz, 3 H), 2.61-2.55 (m, 4 H), 2.12-1.95 (m, 3 H), 1.91-1.80 (m, 1 H), 1.76-1.64 (m, 1 H), 1.62-1.48 (m, 1 H). NOE experiments suggested trans stereochemistry for this compound. LCMS (ESI) calcd for C25H28FN5O2 [M + H] + m / z 450.22, found 450.40. 2trans-b TH NMR (400 MHz, DMSO-d6, ppm) 6: 11.32 (s, 1 H), 8.42-8.33 (m, 1 H), 8.27 (d, J = 2.4 Hz, 1 H), 7.83 (d, J = 8.8 Hz, 1 H), 7.77 (dd, J = 9.2, 2.4 Hz, 1 H), 7.73-7.64 (m, 1 H), 7.60-7.51 (m, 1 H), 7.39 (dd, J = 8.8, 2.8 Hz, 1 H), 6.47 (s, 1 H), 3.35-3.32 (m, 4 H), 3.12-3.00 (m, 1 H), 2.89-2.81 (m, 1 H), 2.78 (d, J = 4.8 Hz, 3 H), 2.61-2.55 (m, 4 H), 2.12-1.93 (m, 3 H), 1.90-1.80 (m, 1 H), 1.76-1.64 (m, 1 H), 1.60-1.48 (m, 1 H). NOE experiments suggested trans stereochemistry for this compound. LCMS (ESI) calcd for C25H28FN5O2 [M + H] + m / z 450.22, found 450.40. Example 3: synthesis oflcis-a, Icis-b, Itrans-a, Itrans-b Na2CO3, dioxane, H2O, 100 °C TMSI ACN, 50 °C Preparation of 3-chloro-l-methoxyisoquinoline (1202) To a solution of 1,3-dichloroisoquinoline 1201 (5.0 g, 25.2 mmol) in MeOH (100 mL) was added MeONa (4.1 g, 75.6 mmol). The mixture was heated at 80 °C for 16 hours. The resulting mixture was diluted with water (500 mL) and extracted with EtOAc (200 mL x 3). The combined organic phases were washed with brine, dried over sodium sulfate, concentrated, and purified by silica gel column chromatography (eluting with EtOAc / PE, 30 % to 60 %) to give 3-chloro-l-methoxyisoquinoline 1202 (5.0 g, 90 % purity, 92 % yield) as a white solid. LCMS (ESI) calcd for CwHsCINO [M + H] + m / z 194.03, found 193.90. Preparation of 3-(l-methoxyisoquinolin-3-yl)cyclopent-2-en-l-one (1203) A mixture of 3-chloro-l-methoxyisoquinoline 1202 (1.00 g, 5.20 mmol), 3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)cyclopent-2-en-l-one 1002 (1.62 g, 7.80 mmol), RuPhos Pd G3 (0.44 g, 0.52 mmol), RuPhos (0.73 g, 1.56 mmol) and NazCOs (1.65 g, 15.60 mmol) in dioxane (30 mL) and H2O (3 mL) was heated at 100 °C for 2 hours under an atmosphere of N2. After cooling to ambient temperature, the mixture was filtered through celite, and the filtrate was concentrated under vacuum. The residue was diluted with water and extracted with EtOAc. The combined organic phases were washed with water and brine, dried over sodium sulfate, concentrated under vacuum, and purified by flash chromatography (eluting with EtOAc / PE, 30 % to 60 %) to obtain 3-(l-methoxyisoquinolin-3-yl)cyclopent-2-en-l-one 1203 (1 g, 90 % purity, 73 % yield) as a white solid. LCMS (ESI) calcd for C15H13NO2 [M + H] + m / z 240.10, found 239.90. Preparation of benzyl 4-(3-(l-methoxyisoquinolin-3-yl)cyclopent-2-en-l-yl)piperazine-l-carboxylate (1205) To a solution of 3-(l-methoxyisoquinolin-3-yl)cyclopent-2-en-l-one 1203 (1.0 g, 4.2 mmol) in MeOH (30 mL) were added benzyl piperazine-l-carboxylate 1204 (1.4 g, 6.3 mmol), AcOH (0.5 g, 8.4 mmol) and NaBHsCN (2.64 g, 41.9 mmol) at room temperature. The reaction mixture was stirred at 60 °C for 24 h. The resulting solution was quenched with water and concentrated under reduced pressure. The residue was purified by flash chromatography (eluting with EtOAc / PE, 50 % to 70 %) to give a mixture of benzyl 4-(3-(l-methoxyisoquinolin- 3-yl)cyclopent-2-en-l-yl)piperazine-l-carboxylate 1205 and benzyl 4-(3-(1-methoxyisoquinolin-3-yl)cyclopentyl)piperazine-l-carboxylate 1205a (1.2 g, 90 % purity, ~57 % yield) as a white solid. LCMS (ESI) calcd for C27H29N3O3 [M + H] + m / z 444.22, found 444.05. Preparation of l-methoxy-3-(3-(piperazin-l-yl)cyclopentyl)-5,6,7,8-tetrahydroisoquinoline (1206) To a solution of a mixture of benzyl 4-(3-(l-methoxyisoquinolin-3-yl)cyclopent-2-en-l-yl)piperazine-l-carboxylate 1205 and benzyl 4-(3-(l-methoxyisoquinolin-3-yl)cyclopentyl)piperazine-l-carboxylate 1205a (1.2 g, ~2.7 mmol) in TEA (20 mL) was added PtO2 (0.6 g, 2.7 mmol). The mixture was evacuated and backfilled with hydrogen three times and then charged with hydrogen. The resulting mixture was stirred at room temperature for 16 hours under H2 atmosphere. The mixture was filtered through celite, and the filtrate was concentrated under vacuum to give crude l-methoxy-3-(3-(piperazin-l-yl)cyclopentyl)-5,6,7,8-tetrahydroisoquinoline 1206 (1.2 g, 60 % purity, 85 % yield) as a yellow oil which was used directly in next step without further purification. LCMS (ESI) calcd for C19H29N3O [M + H] + m / z 316.23, found 316.20. Preparation of methyl 5-(4-(3-(l-methoxy-5,6,7,8-tetrahydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)picolinate (1208) To a solution of l-methoxy-3-(3-(piperazin-l-yl)cyclopentyl)-5,6,7,8-tetrahydroisoquinoline 1206 (1.1 g, 3.5 mmol) in DMSO (30 mL) were added methyl 5-fluoropicolinate 1207 (0.8 g, 5.2 mmol) and DIPEA (2.3 g, 17.5 mmol). The mixture was heated at 100 °C for 1 h. The resulting mixture was diluted with water (200 mL) and extracted with EtOAc (100 mLx 3). The combined organic phases were washed with brine, dried over sodium sulfate, concentrated, and purified by silica gel column chromatography (eluting with EtOAc / PE, 50 % to 80 %) to give methyl 5-(4-(3-(l-methoxy-5,6,7,8-tetrahydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)picolinate 1208 (500 mg, 90 % purity, 28 % yield) as a white solid. LCMS (ESI) calcd for C26H34N4O3 [M + H] + m / z 451.27, found 451.20. Preparation            of            5-(4-(3-(l-methoxy-5,6,7,8-tetrahydroisoquinolin-3- yl)cyclopentyl)piperazin-l-yl)-N-methylpicolinamide (1209) A solution of methyl 5-(4-(3-(l-methoxy-5,6,7,8-tetrahydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)picolinate 1208 (500 mg, 1.1 mmol) in MeNFh-MeOH (10 mL, 30% wt.) was heated at 80 °C for 2 hours. The resulting mixture was concentrated to give 5-(4-(3-(l-methoxy-5,6,7,8-tetrahydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)-N-methylpicolinamide 1209 (500 mg, 90 % purity, 90 % yield) as a yellow solid. LCMS (ESI) calcd for C26H35N5O2 [M + H] + m / z 450.28, found 450.30. Preparation of N-methyl-5-(4-(3-(l-oxo-l,2,5,6,7,8-hexahydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)picolinamide (Icis-a / Icis-b / ltrans-a / Itrans-b) To a solution of 5-(4-(3-(l-methoxy-5,6,7,8-tetrahydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)-N-methylpicolinamide 1209 (500 mg, 1.11 mmol) in ACN (20 mL) was added TMSI (667 mg, 3.34 mmol). The mixture was heated at 50 °C for 2 hours. The resulting mixture was diluted with water (200 mL) and extracted with EtOAc (100 mL x 3). The combined organic phases were washed with brine, dried over sodium sulfate, concentrated, and purified by silica gel column chromatography (eluting with MeOH / DCM, 5 % to 10 %). The resulting solid was separated by SFC (Column: Torus 2-PIC OBD 20 mm I.D. x 250 mm, 5 pm; Mobile phase: CO2 / MeOH [0.1 % (NH3)] = 25 / 75) to afford the first fraction as N-methyl-5-(4-(3-(l-oxo-l,2,5,6,7,8-hexahydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)picolinamide lcis-a / Icis-b racemic mixture (cis, 20 mg, 90 % purity, 3 % yield, white solid) and the second fraction as N-methyl-5-(4-(3-(l-oxo-l,2,5,6,7,8-hexahydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)picolinamide ltrans-a / ltrans-b racemic mixture (trans, 20 mg, 90 % purity, 3 % yield, white solid). Preparation of N-methyl-5-(4-(3-(l-oxo-l,2,5,6,7,8-hexahydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)picolinamide (lcis-a and Icis-b) lcis-a / Icis-b racemic mixture was separated by SFC (Column: Daicel ChiraIpak-lH 20 mm I.D. x 250 mm, 5 pm; Mobile phase: CO2 / MeOH [0.1 % (NH3)] = 70 / 30) and concentrated under reduced pressure to afford the first fraction as lcis-a (4.0 mg, 99.00 % purity, 100 % ee, white solid) and the second fraction as lcis-b (4.0 mg, 95.74 % purity, 100 % ee, white solid). lcis-a XH NMR (400 MHz, DMSO-de, ppm) 6: 11.50 (s, 1 H), 8.45-8.33 (m, 1 H), 8.28 (s, 1 H), 7.84 (d, J = 8.8 Hz, 1 H), 7.47-7.34 (m, 1 H), 5.81 (s, 1 H), 3.48-3.35 (m, 4 H), 3.02-2.89 (m, 1 H), 2.78 (d, J = 4.8 Hz, 3 H), 2.69-2.60 (m, 5 H), 2.45-2.40 (m, 2 H), 2.28-2.21 (m, 2 H), 2.13-1.96 (m, 2 H), 1.86-1.72 (m, 2 H), 1.68-1.53 (m, 6 H). NOE experiments suggested cis stereochemistry for this compound. LCMS (ESI) calcd for C25H33N5O2 [M + H] + m / z 436.27, found 436.20. lcis-b XH NMR (400 MHz, DMSO-de, ppm) 6: 11.50 (s, 1 H), 8.40 (q, J = 4.6 Hz, 1 H), 8.27 (d, J = 2.8 Hz, 1 H), 7.84 (d, J = 8.8 Hz, 1 H), 7.40 (dd, J = 8.8, 2.8 Hz, 1 H), 5.81 (s, 1 H), 3.50-3.40 (m, 4 H), 3.01-2.88 (m, 1 H), 2.78 (d, J = 4.8 Hz, 3 H), 2.67-2.58 (m, 5 H), 2.45-2.41 (m, 2 H), 2.29-2.22 (m, 2 H), 2.12-1.98 (m, 2 H), 1.85-1.71 (m, 2 H), 1.67-1.53 (m, 6 H). NOE experiments suggested cis stereochemistry for this compound. LCMS (ESI) calcd for C25H33N5O2 [M + H] + m / z 436.27, found 436.25. Preparation of N-methyl-5-(4-(3-(l-oxo-l,2,5,6,7,8-hexahydroisoquinolin-3-yl)cyclopentyl)piperazin-l-yl)picolinamide (Itrans-a and Itrans-b) Itrans-a / trans-b racemic mixture was separated by SFC (Column: Daicel ChiraIpak-lH 20 mm LD. x 250 mm, 5 pm; Mobile phase: CO2 / MeOH [0.1 % (NH3)] = 70 / 30) and concentrated under reduced pressure to afford the first fraction as ltrans-a (5.2 mg, 99.16 % purity, 100% ee, white solid) and the second fraction as ltrans-b (5.2 mg, 99.39 % purity, 100% ee, white solid). Itrans-a XH NMR (400 MHz, DMSO-d6, ppm) 5: 11.11 (s, 1 H), 8.48-8.35 (m, 1 H), 8.26 (d, J = 2.8 Hz, 1 H), 7.83 (d, J = 8.8 Hz, 1 H), 7.39 (dd, J = 8.8, 2.8 Hz, 1 H), 5.77 (s, 1 H), 3.31-3.28 (m, 4 H), 2.99-2.87 (m, 1 H), 2.85-2.74 (m, 4 H), 2.57-2.53 (m, 4 H), 2.46-2.41 (m, 2 H), 2.29-2.23 (m, 2 H), 2.03-1.88 (m, 3 H), 1.82-1.68 (m, 1 H), 1.67-1.44 (m, 6 H). NOE experiments suggested trans stereochemistry for this compound. LCMS (ESI) calcd for C25H33N5O2 [M + H] + m / z 436.27, found 436.25. Itrans-b TH NMR (400 MHz, DMSO-d6, ppm) 6: 6 11.12 (s, 1 H), 8.49-8.32 (m, 1 H), 8.26 (s, 1 H), 7.83 (d, J = 8.4 Hz, 1 H), 7.48-7.26 (m, 1 H), 5.77 (s, 1 H), 3.31-3.29 (m, 4 H), 2.96-2.88 (m, 1 H), 2.81-2.72 (m, 4 H), 2.57-2.53 (m, 4 H), 2.46-2.42 (m, 2 H), 2.30-2.23 (m, 2 H), 2.00-1.91 (m, 3 H), 1.79-1.71 (m, 1 H), 1.64-1.46 (m, 6 H). NOE experiments suggested trans stereochemistry for this compound. LCMS (ESI) calcd for C25H33N5O2 [M + H] + m / z 436.27, found 436.25. Example 4: Assays Exemplary compounds of the invention were prepared and tested to determine their effect as PARP1 and PARP2 inhibitors. Typical assays are described below. Example 4A. PARP1 biochemical dissociation-enhanced lanthanide fluorescence immunoassay (DELFIA assay) Optiplate HB 384-well plates were coated with anti-FLAG antibody, supplied as a 4 mg / ml solution, using a Na2CO3 / HCO3 coating buffer at pH 9.6, overnight at 4 °C, in order to achieve a final immobilisation per well of 0.3 ug. Wells were then washed 3x5 min in coating wash buffer (PBS / 0.05 % Tween (v / v)), and blocked with 2 % BSA (w / v) in coating wash buffer overnight at 4 °C. Prior to assay, wells were washed 3x5 min in coating wash buffer. For the assay 20 pl of 2.5 nM recombinant full length human N-terminally FLAG-tagged PARP1 was added to each well of the 384-well plate for 30 min at room temperature followed by addition of 50 nL of compound solution in DMSO using pintool technology. Following incubation for 30 min at room temperature, 5 pl of 10 uM biotin-NAD+ and 10 nM activation DNA (sequence shown below) in solution in 20 mM HEPES (pH 7.5), 100 mM NaCI, 2 mM DTT, 0.1 % BSA (w / v), 0.02 % Tween (v / v) assay buffer. Auto-PARylation proceeded for 2 h at room temperature prior to the addition of 5 pl of 12 mM NAD+ quenching solution. After 30 min at room temperature, assay solution was removed and following washing 5 times for 3 min, 100 pl of a 1:1000 dilution of DELFIA Eu-Nl Streptavidin reagent was added. Plates were then incubated for 30 min at room temperature. The reaction mixture was removed and the plates washed 5 times for 3 min prior to the addition of 25 jllI DELFIA enhancement solution. Following incubation for 30 min at room temperature, fluorescence was measured on a Pherastar FS (Ex337 nm, Em620 nm; integration start 60 ps; integration time 400 ps). Typically compounds were tested from 20 pM at 3-fold dilution intervals in 12-point concentration-response curves to determine IC50 values. Data was analysed using ActivityBase software and replicate values for the low (without enzyme, 0.2 % DMSO) and high (0.2 % DMSO) % controls were averaged and the data obtained from the test compounds expressed as a % of 100 % using the below formulae: % value = 100-(100*((high control - unknown) / (high control - low control)) % data was fitted to a non-linear regression equation (log inhibitor vs response-variable slope 4-parameters) to obtain IC50 values. The IC50 values for a variety of test compounds are shown in Table 1. Activation DNA sequence: S^ACGCTGCTGTGGOOdew (SEQ ID NO:1) ^ATCACCTTGTTCTCCAHGCCCACAGCAGGGT^' (SEQ ID NO:2) S’ - “3’(SEQ ID NO:3) ( H is H H 11 El IH H H Example 4B. PARP1 probe displacement homogeneous time-resolved fluorescence assay (HTRF assay) 10 nM full length N-terminally FLAG-tagged PARP1 was incubated with 2 nM Anti-FLAG Tb-cryptate antibody and PARP1 / 2 Cy5 fluorescent dye-labelled binding probe (10-fold probe Kd = 270 nM) in 20 mM HEPES (pH 7.5), 100 mM NaCI, 2 mM DTT, 0.1 % BSA (w / v), 0.02 % Tween (v / v) assay buffer for 40 min at room temperature. A Cy5-labelled binding probe is shown below and described in Papeo, G. et al. J. Biomol. Screen. 2014; 19:1212-1219. 6 pl of this reaction mixture was then transferred to each well of a black non-binding surface 384-well plate and 35 nl of compound solution in DMSO was then added using pintool technology. Following incubation for 1 h at room temperature, fluorescence was measured on a Pherastar FS (Ex 337 nm, Em620 nm, em665 nm; integration start 60 ps; integration time 400 ps) using the HTRF module. Typically compounds were tested from 58.5 pM at factor 3 dilution intervals in 12-point concentration-response curves to determine IC50 values. Data was analysed using ActivityBase software and replicate values for the low (without enzyme but with probe and Tb-cryptate antibody, 0.6 % DMSO) and high (0.6 % DMSO) % controls were averaged and the data obtained from the test compounds expressed as a % of 100 % using the below formulae: %activity = 100*(value - low control) / (high control - low control) %activity data was fitted to a non-linear regression equation to obtain IC50 values Kd values were calculated using Cheng-Prussoff formula: IC50 = (1+ ([probe concentration] / [KmProbe]))*Kd Therefore Kd = IC50 / (l+[[probe concentration] / [Kmprobe])); using probe at 10 x Km, this equated to Kd = IC50 / H Example 4C. PARP2 probe displacement homogeneous time-resolved fluorescence assay (HTRF assay) This assay was performed under identical conditions as for PARP1, except that N-terminally FLAG-tagged PARP2 (amino acids 1-583) was used instead of PARP1, and PARP1 / 2 binding probe was used at 10-fold probe Kd = 540 nM. Data analysis was performed identical as for PARP1. Cy5 probe structure: NanoBRET cellular target occupancy assay NanoBRET assays were employed to demonstrate cellular target engagement and selectivity at PARP1 and PARP2. These assays are based on bioluminescence resonance energy transfer (BRET) between a Nano-luc-tagged protein (eg PARP1 or PARP2) and a fluorescent group on a high affinity NAD+ competitive binding probe. Such cellular probe displacement assays can be utilised to measure inhibitor affinities and selectivity ratios at PARP1 and 2. Frozen HEK293 cells transiently transfected with either PARPl-NanoLuc® fusion or PARP2-NanoLuc® fusion constructs (Promega) were thawed and dispensed as a suspension in 384-well microplates each at a density of 1750 cells per well. NanoBRET™ TE PARP Tracer-01 was then added to final concentrations of 11 and 2 nM for PARP1 and PARP2 assays, respectively. Compounds were added from 25 pM at factor 3 dilution intervals in 12-point concentration response curves and plates were incubated for 2 hours at 37 °C. BRET ratios were then measured using a NanoBRET module (LUM 610-LP 450-80) and PHERAstar FS or FSX reader following addition of NanoBRET™ Nano-Gio® Substrate and Extracellular NanoLuc® Inhibitor according to manufacturer's instructions. Kd values were calculated using Cheng-Prussoff 5 formula: IC50 = (1+ ([tracer concentration] / [Kmtracer])) * Kd Binned potency, affinity and selectivity data for a variety of test compounds are shown in Table 1 where DELFIA and Probe Displacement HTRF assays were used. Binned potency, 10 affinity and selectivity data for a subset of test compounds where the NanoBRET assay was used are shown in Table 1. TABLE 1 Results ofParp 1 / 2 assays for selected compounds (DELFIA and Probe Displacement HTRF) Compound PARP1 DELFIA PARP1 HTRF PARP2 HTRF Selectivity lcis-a ++++ ++++ ++ +++ Icis-b ++++ ++++ +++ + Itrans-a ++++ ++++ ++ + ltrans-b ++++ ++++ +++ + 2cis-a ++++ ++++ ++ +++ 2cis-b ++++ ++++ ++++ - 2trans-a ++++ ++++ ++ + 2trans-b ++++ ++++ +++ + 3cis-rac ++++ ++++ +++ + 3trans-a ++++ ++++ +++ +4- 3trans-b ++++ ++++ + +++ 4cis-a ++++ ++++ ++ +++ 4cis-b ++++ ++++ ++++ - 4trans-a ++++ ++++ + +++ 4trans-b ++++ ++++ +++ + 5cis-a ++++ ++++ ++ +++ 5cis-b ++++ ++++ ++++ - 5trans-a ++++ ++++ +++ + + 5trans-b ++++ ++++ ++ + + 6cis-a ++++ ++++ ++ +++ 6cis-b ++++ ++++ ++++ - 6trans-a 4-4-4-4- 4-4-4-4- 4- 4-4-4- 6trans-b 4-4-4-4- 4-4-4-4- 4-4-4- 4- TABLE 2 Results ofParp 1 / 2 assays for selected compounds (NanoBRET) Compound PARP1 NanoBRET PARP2 NanoBRET Selectivity lcis-b ++++ +++ + ltrans-b ++++ +++ ++ 2cis-b ++++ +++ + 2trans-b ++++ +++ ++ 3cis-rac ++++ +++ +++ 3trans-a ++++ ++ +++ 4cis-a ++++ ++ +++ 4cis-b ++++ +++ + 4trans-a ++++ - +++ 4trans-b ++++ +++ +++ 5cis-b ++++ +++ + 6cis-a ++++ ++ +++ 6cis-b ++++ +++ + 6trans-b ++++ +++ ++ Key DELFIA, Probe Displacement HTRF and NanoBRET assay categories: - indicates IC50 or Kd value above 10 pM 10 + indicates IC50 or Ka value above 1 pM up to 10 pM ++ indicates IC50 or Ka value above 100 nM up to 1 pM +++ indicates IC50 or Kd value above 10 nM up to 100 nM ++++ indicates IC50 or Kd value of 10 nM or less Selectivity categories: - indicates a value of less than 10 5 + indicates a value of 10 to less than 50 ++ indicates a value of 50 to less than 100 +++ indicate a value of at least 100 The selectivity values relate to the selectivity preference of PARP1 over PARP2. They are 10 calculated from the ratio of Kd values for PARP1 and PARP2 inhibition as Kd (PARP2) / Kd (PARP1). It will be appreciated that the above embodiments have been described by way of example 15 only. Other variants or use cases of the disclosed techniques may become apparent to the person skilled in the art once given the disclosure herein. The scope of the disclosure is not limited by the described embodiments but only by the accompanying claims.

Claims

1. A PARP1 inhibitor compound having a structure of:wherein:a dotted line represents a bond selected from a single bond and a double bond;y is 0,1, or 2;ring D is aromatic or non-aromatic;each XD is independently selected from C, O, and N; with the provisos that:no more than one XD is O; andwhen an XD is O or N, ring D is non-aromatic;each R1 is independently absent, or present and selected from H and a substituted or unsubstituted organic group;each R4 is independently absent or selected from:H;a halogen;C(R9)i, wherein i is an integer in the range 1 to 3;OR9; andS(R9)j, where j is an integer in the range 1 to 5;wherein each R9 is independently selected from H and a substituted or unsubstituted organic group;R2 and R3 are each independently selected from H and a substituted or unsubstituted organic group; andL is a group having a structure of:wherein:X1, X3, X4 and X5 are each independently selected from C and N;each X2 is independently selected from C, N, O, and S;n is 0,1, 2, 3, 4,or 5;m is 0,1, 2, 3, 4,or 5, with the proviso that n + m is in the range 2 to 5;p is 1, 2 or 3;q is 1, 2 or 3, with the proviso that p + q is in the range 2 to 5;r is 0,1, 2, 3, 4,or 5;s is 0,1, 2, 3, 4, or 5, with the proviso that r + s is in the range 2 to 5;each R5A, R5B, and R5C is independently absent or selected from H and a substituted or unsubstituted organic group;R6 is absent or selected from H and a substituted or unsubstituted organic group; andQ is a bond or a linking group having a structure selected from:wherein:t is 0, 1, 2, 3, 4 or 5;u is 0,1, 2, 3, 4 and 5, with the proviso that t + u is in the range 0 to 6; andeach R7 and R8 is independently selected from H and a substituted or unsubstituted organic group.

2. The PARP1 inhibitor compound according to claim 1, wherein each R1 and each R4 is independently absent or selected from:H;a halogen;a nitrile group;a Cl to C6 alkyl group, such as a C3 to C6 cycloalkyl group;a Cl to C6 alkoxy group;a Cl to C6 haloalkoxy group, such as -OCF3 or OCHF2;a haloalkyl group; andR22 being selected from H, a halogen, a Cl to C6 alkyl group, a C3 to C6 cycloalkyl group, a Cl to C6 alkoxy group, a Cl to C6 haloalkyl group, andeach R23 being independently selected from H, a halogen, a Cl to C6 linear or branched alkyl group, a Cl to C6 linear or branched aminoalkyl group, a Cl to C6 alkoxy group, a Cl to C6 haloalkoxy group, such as -OCF3 or OCHF2; and a Cl to C6 haloaIkyl group.

3. The PARP1 inhibitor compound according to claim 2, wherein each R1 and each R4 is independently absent or selected from H; a halogen, optionally Cl or F; a Cl to C3 alkyl group, optionally a methyl group; a Cl to C3 haloalkyl group, optionally a halomethyl group such as -CH2F, -CHF2, or-CFs; a haloethyl group, such as -CH2CF3; and a nitrile group.

4. The PARP1 inhibitor compound according to claim 3, wherein each R1 and each R4 is independently absent or selected from: H; Cl; F; a halomethyl group, such as CF3; and a nitrile group.

5. The PARP1 inhibitor compound according to claim 4, wherein each R1 and each R4 is independently absent or selected from H and F;optionally wherein each R4 is H.

6. The PARP1 inhibitor compound according to claim 5, wherein exactly one R1 or exactly one R4 is F.

7. The PARP1 inhibitor compound according to any preceding claim, wherein y is 1.

8. The PARP1 inhibitor compound according to any preceding claim, wherein each XD is9. The PARP1 inhibitor compound according to claim 8, having a structure of:optionally10. The PARP1 inhibitor compound according to claim 9, having a structure of:

11. The PARP1 inhibitor compound according to claim 9, having a structure selected from12. The PARP1 inhibitor compound according to any of claims 1 to 8, wherein ring D isnon-aromatic.from:from:

15. The PARP1 inhibitor compound according to claim 14, having a structure of:and preferably having a structure of:17.The PARP1 inhibitor compound according to claim16, having a structure selectedfrom:

18. The PARP1 inhibitor compound according to any preceding claim, wherein R2 is selected from H; a halogen, optionally F or Cl; a Cl to C3 alkyl group, optionally an isopropyl group or a cyclopropyl group; a Cl to C3 haloalkyl group, optionally -CH2F, -CHF2, -CF3, -CH2CF3, or -CH2CH2F; a Cl to C3 alcohol group, optionally -CH2CH2OH; a Cl to C3 alkoxy group,optionally a methoxy group, a methoxymethyl group, or methoxyethyl group; and a Cl to C3 aminoalkyl group.

19. The PARP1 inhibitor compound according to claim 18, wherein R2 is H.

20. The PARP1 inhibitor compound according to any preceding claim, wherein R3 is selected from H, a Cl to C3 alkyl group, and a Cl to C3 haloalkyl group.

21. The PARP1 inhibitor compound according to claim 20, wherein R3 is H.

22. The PARP1 inhibitor compound according to any preceding claim, having a structureselected from:

23. The PARP1 inhibitor compound according to any preceding claim, wherein both n andm are at least 1.

24. The PARP1 inhibitor compound according to claim 23, wherein:i) ring A is a 7-membered ring, optionally a cycloheptane having a structure selected from:each R5A and R5A3 being independently selected from H and a substituted or unsubstituted organic group, wherein R5A3 is most preferably H; orii) ring A is a 6-membered non-aromatic ring, optionally a cyclohexane, cyclohexene, or tetrahydropyran and further optionally having a structure selected from:each R5A and R5A3 being independently selected from H and a substituted or unsubstituted organic group, wherein R5A3 is most preferably H; oriii) ring A is a 5-membered non-aromatic ring, optionally a cyclopentane, cyclopentene, or atetrahydrofuran, and further optionally having a structure selected from:each R5A and R5A3 being independently selected from H and a substituted or unsubstituted organic group, wherein R5A3 is most preferably H; oriv) ring A is a 4-membered ring having a structure of:each R5A and R5A3 being independently selected from H and a substituted or unsubstituted organic group, wherein R5A3 is most preferably H; orv) ring A is a bridged ring, optionally having a structure selected from:each R5A and R5A3 being independently selected from H and a substituted or unsubstituted organic group, wherein R5A3 is most preferably H.

25. The PARP1 inhibitor compound according to any preceding claim, wherein ring A is asaturated ring.

26. The PARP1 inhibitor compound according to any preceding claim, wherein when present each R5A is independently selected from H; a halogen, optionally F; a hydroxyl group; a carbonyl group; and a Cl to C3 alkyl group, optionally wherein a pair of R5A groups form a ring, further optionally wherein the ring bridges ring A;preferably wherein each R5A is H.

27. The PARP1 inhibitor compound according to claim 24, wherein ring A has a structureselected from:MW IQbOwhere Qa represents a bond to ring E and Qb represents a bond to ring B.

28. The PARP1 inhibitor compound according to claim 23, wherein ring A has a structureof:wherein:Qa represents a bond to ring E and Qb represents a bond to ring B;m is 1 or 2;n is 1 or 2;each R5A2 and R5A3 independently is absent or selected from H and a substituted or unsubstituted organic group, preferably wherein R5A3 is H;and wherein:i) XI is C and R5A1 is selected from H and a substituted or unsubstituted organic group;orii) XI is N and R5A1 is absent.

29. The PARP1 inhibitor compound for use according to claim 28, wherein each R5A2independently is absent or H.selected from:(to ring E)(to ring B)(to ring E)(to ring E)(to ring B)preferably wherein ring A has a structure of:(to ring E)(to ring E)31. The PARP1 inhibitor compound according to any preceding claim, wherein ring B hasa structure of:

32. The PARP1 inhibitor compound according to any preceding claim, wherein X3 is N.

33. The PARP1 inhibitor compound according to claim 31, wherein ring B has a structureselected from:5B R5B R5B 5B34. The PARP1 inhibitor compound according to any preceding claim, wherein each R5B is independently absent or H.

35. The PARP1 inhibitor compound according to claim 33, wherein ring B has a structure36. The PARP1 inhibitor compound according to claim 35, wherein ring B has a structureof:37.The PARP1 inhibitor compound according to any preceding claim, wherein Q. iswherein t + u is at least 1; andwherein R7 is selected from H; a halogen, such as -F, -Cl, -Br, and -I, and preferably -F; an -OH group; a Cl to C6 alkyl group; a Cl to C6 haloalkyl group, preferably CF3; an -NH2 group; a Cl to C6 amino group; a Cl to C6 alcohol group; and a Cl to C6 alkoxygroup.

38. The PARP1 inhibitor compound according to claim 37, wherein R7 is selected from: H; a halogen, optionally F; a Cl to C6 alkyl group; and a Cl to C6 haloalkyl group.

39. The PARP1 inhibitor compound according to any preceding claim, wherein Q has a structure of:and wherein R8 is selected from:H;a substituted or unsubstituted linear or branched Ci-Ce alkyl group (such as Me, Et, Pr, i-Pr, n-Bu, i-Bu, t-Bu, pentyl and hexyl);a substituted or unsubstituted linear or branched Ci-Ce alkyl-aryl group(such as -CH2Ph, -CH2(2,3 or 4)F-Ph, -CH2(2,3 or 4)CI-Ph, -CH2(2,3 or 4)Br-Ph,-CH2(2,3 or4)l-Ph, -CH2CH2Ph, -CH2CH2CH2Ph,-CH2CH2CH2CH2Ph, -CH2CH2CH2CH2CH2Ph, and -CH2CH2CH2CH2CH2CH2Ph);a substituted or unsubstituted linear or branched Ci-Ce halogenated alkyl group (such as -CH2F, -CFS, -CH2CH2F and -CH2CF3);a substituted or unsubstituted cyclic amine or amido group(such as pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, 2-keto-pyrrolidinyl, 3-keto-pyrrolidinyl, 2-keto-piperidinyl, 3-keto-piperidinyl, and 4-keto-piperidinyl);a substituted or unsubstituted cyclic C3-C8 alkyl group(such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl);a substituted or unsubstituted linear or branched C2-Ce alcohol group (such as -CH2CH2OH, -CH(CH3)CH2OH, -C(CH3)2OH, -CH2CH2CH2OH, -CH2CH2CH2CH2OH, -CH(CH3)CH2CH2OH, -CH(CH3)CH(CH3)OH, -CH(CH2CH3)CH2OH, -C(CH3)2CH2OH, -ch2ch2ch2ch2ch2oh, and -CH2CH2CH2CH2CH2CH2OH);a substituted or unsubstituted linear or branched C2-Ce carboxylic acid group (such as -CH2COOH, -CH2CH2COOH, -CH2CH2CH2COOH, -CH2CH2CH2CH2COOH, and -CH2CH2CH2CH2CH2COOH);a substituted or unsubstituted linear or branched carbonyl group(such as -(CO)Me, -(CO)Et, -(CO)Pr, -(CO)-i_Pr, -(CO)-n-Bu, -(CO)-i-Bu, -(CO)-t-Bu, -(CO)Ph, -(CO)CH2Ph, -(CO)CH2OH, -(CO)CH2OCH3, -(CO)CH2NH2, -(CO)CH2NHMe, -(CO)CH2NMe2, -(CO)-cyclopropyl, -(CO)-l,3-epoxypropan-2-y I; -(CO)NH2, -(CO)NHMe, -(CO)NMe2, -(CO)NHEt, -(CO)NEt2, -(CO)-pyrollidine-N-yl, -(CO)-morpholine-N-yl, -(CO)-piperazine-N-yl, -(CO)-N-methyl-piperazine -N-yl, -(CO)NHCH2CH2OH, -(CO)NHCH2CH2OMe, -(CO)NHCH2CH2NH2, -(CO)NHCH2CH2NHMe, and -(CO)NHCH2CH2NMe2);a substituted or unsubstituted linear or branched Ci-Ce carboxylic acid ester group (such as -COOMe, -COOEt, -COOPr, -COO-i-Pr, -COO-n-Bu, -COO-i-Bu, -COO-t-Bu, -CH2COOMe, -CH2CH2COOMe, -CH2CH2CH2COOMe, and -CH2CH2CH2CH2COOMe);a substituted or unsubstituted linear or branched Ci-Ce amide group(such as -CO-NH2, -CO-NMeH, -CO-NMe2, -CO-NEtH, -CO-NEtMe, -CO-NEt2, -CO-NPrH, -CO-NPrMe, and -CO-NPrEt);a substituted or unsubstituted sulfonyl group(such as -SO2Me, -SO2Et, -SO2Pr, -SO2iPr, -SO2Ph, -SO2-(2,3 or 4)-F-Ph, -SO2-cyclopropyl, -SO2CH2CH2OCH3), -SO2NH2, -SO2NHMe, -SO2NMe2, -SO2NHEt, -SO2NEt2, -SO2-pyrrolidine-N-yl,-SO2-morpholine-N-yl, -SO2NHCH2OMe, and -SO2NHCH2CH2OMe);a substituted or unsubstituted aromatic group(such as Ph-, 2-F-Ph-, 3-F-Ph-, 4-F-Ph-, 2-CI-Ph-, 3-CI-Ph-, 4-CI-Ph-, 2-Br-Ph-, 3-Br-Ph-, 4-Br-Ph-, 2-l-Ph-, 3-l-Ph, 4-l-Ph-, 2,(3,4,5 or 6)-F2-Ph-, 2,(3,4,5 or 6)-CI2-Ph-, 2,(3,4,5 or 6)-Br2-Ph-, 2,(3,4,5 or 6)-l2-Ph-, 2,(3,4,5 or 6)-Me2-Ph-, 2,(3,4,5 or 6)-Et2-Ph-, 2,(3,4,5 or 6)-Pr2-Ph-, 2,(3,4,5 or 6)-Bu2-Ph-, 2,(3,4,5 or 6)-(CN)2-Ph-, 2,(3,4,5 or 6)-(NO2)2-Ph-, 2,(3,4,5 or 6)-(NH2)2-Ph-, 2,(3,4,5 or 6)-(MeO)2-Ph-, 2,(3,4,5 or 6)-(CF3)2-Ph-, 3,(4 or 5)-F2-Ph-, 3,(4 or 5)-CI2-Ph-, 3,(4 or 5)-Br2-Ph-, 3,(4 or 5)-12-Ph-, 3,(4 or 5)-Me2-Ph-, 3,(4 or 5)-Et2-Ph-, 3,(4 or 5)-Pr2-Ph-, 3,(4 or 5)-Bu2-Ph-, 3,(4 or 5)-(CN)2-Ph-, 3,(4 or 5)-(NO2)2-Ph-, 3,(4 or 5)-(NH2)2-Ph-, 3,(4 or 5)-(MeO)2-Ph-, 3,(4 or 5)-(CF3)2-Ph-, 2-Me-Ph-, 3-Me-Ph-, 4-Me-Ph-, 2-Et-Ph-, 3-Et-Ph-, 4-Et-Ph-, 2-Pr-Ph-, 3-Pr-Ph-, 4-Pr-Ph-, 2-Bu-Ph-, 3-Bu-Ph-,4-Bu-Ph-, 2-(CN)-Ph-, 3-(CN)-Ph-, 4-(CN)-Ph-, 2-(NO2)-Ph-, 3-(NO2)-Ph-, 4-(NO2)-Ph-, 2-(NH2)-Ph-, 3-(NH2)-Ph-, 4-(NH2)-Ph-, 2-MeO-Ph-, 3-MeO-Ph-, 4-MeO-Ph-, 2-(NH2-CO)-Ph-, 3-(NH2-CO)-Ph-, 4-(NH2-CO)-Ph-, 2-CF3-Ph-, 3-CF3-Ph-, 4-CF3-Ph-, 2-CF3O-Ph-, 3-CF3O-Ph-, and 4-CF3O-Ph-); and a substituted or unsubstituted heterocyclic group(such as pyrrole-2-yl, pyrrole-3-yl, pyrazole-3-yl, pyrazole-4-yl, pyrazole-5-yl, imidazole-2-yl, imidazole-4-yl, imidazole-5-yl, l,2,3-triazole-4-yl, l,2,3-triazole-5-yl, l,2,4-triazole-3-yl, l,2,4-triazole-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazine-3-yl, pyridazine-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrimidin-6-yl, pyrazine-2-yl, pyrrolidine-2-yl, pyrrolidine-3-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, 2-azapiperidine-3-yl, 2-azapiperidine-4-yl, 3-azapiperidine-2-yl, 3-azapiperidine-4-yl, 3-azapiperidine-5-yl, piperazine-2-yl, furan-2-yl, furan-3-yl, pyran-2-yl, pyran-3-yl, pyran-4-yl, 2-azapyran-3-yl, 2-azapyran-4-yl, 2-azapyran-5-yl, 2-azapyran-6-yl, 3-azapyran-2-yl, 3-azapyran-4-yl, 3-azapyran-5-yl, 3-azapyran-6-yl, 4-azapyran-2-yl, 4-azapyran-3-yl, 4-azapyran-5-yl, 4-azapyran-6-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-4-yl, 2-aza-tetrahydrofuran-5-yl, 3-aza-tetrahydrofuran-2-yl, 3-aza-tetrahydrofuran-4-yl, 3-aza-tetrahydrofuran-5-yl, tetrahydropyran-2-yl, oxetan-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, 2-aza-tetrahydropyran-3-yl, 2-aza-tetrahydropyran-4-yl, 2-aza-tetrahydropyran-5-yl, 2-aza-tetrahydropyran-6-yl, 3-aza-tetrahydropyran-2-yl, 3-aza-tetrahydropyran-4-yl, 3-aza-tetrahydropyran-5-yl, 3-aza-tetrahydropyran-6-yl, morpholine-2-yl, morpholine-3-yl, thiophen-2-yl, thiophen-3-yl, isothiazole-3-yl, isothiazole-4-yl, isothiazole-5-yl, thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, thiopyran-2-yl, thiopyran-3-yl, thiopyran-4-yl, 2-azathiopyran-3-yl, 2-azathiopyran-4-yl, 2-azathiopyran-5-yl, 2-azathiopyran-6-yl, 3-azathiopyran-2-yl, 3-azathiopyran-4-yl, 3-azathiopyran-5-yl, 3-azathiopyran-6-yl, 4-azathiopyran-2-yl, 4-azathiopyran-3-yl, 4-azathiopyran-5-yl, 4-azathiopyran-6-yl, thiolane-2-yl, thiolane-3-yl,thiane-2-yl, thiane-3-yl, thiane-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, furazan-3-yl, (l,3,4-oxadiazol)-2-yl, (l,3,4-oxadiazol)-5-yl, (l,2,4-oxadiazol)-3-yl, (l,2,4-oxadiazol)-5-yl; and tetrazole-5-yl).

40. The PARP1 inhibitor compound according to claim 39, wherein R8 is selected from H, a substituted or unsubstituted linear or branched Ci-Ce alkyl group, and a substituted or unsubstituted linear or branched Ci-Ce halogenated alkyl group.

41. The PARP1 inhibitor compound according to any of claims 1 to 36, wherein Q is a bond or -CH2-,preferably wherein Q is a bond.

42. The PARP1 inhibitor compound according to any preceding claim, wherein X3 is C and X4 is C.

43. The PARP1 inhibitor compound according to any preceding claim, wherein both r and s are at least 1,optionally wherein r and s sum to 3 or 4.

44. The PARP1 inhibitor compound according to claim 43, wherein:i) ring C is a 6-membered aliphatic ring, optionally a 6-membered aliphatic ring having structure of:each R5C and R5C1 being independently selected from H and a substituted or unsubstituted organic group, preferably wherein R5C1 is H, more preferably wherein R5C1 anc| r5C js |_|.orii) ring C is a 6-membered aromatic ring, optionally selected from: iia) a phenyl group, optionally having a structure of:each R5C being independently selected from H and a substituted or unsubstituted organic group, optionally wherein each R5C is H;iib) a pyridine group, optionally having a structure selected from:each R5C being independently selected from H and a substituted orunsubstituted organic group, optionally wherein each R5C is H;iic) a diazine group, optionally having a structure selected from:each R5C being independently selected from H and a substituted or unsubstituted organic group, optionally wherein each R5C is H;oriii) ring C is a 5-membered aromatic ring, optionally selected from:iiia) an imidazole group, optionally an imidazole group having a structure selected from:each R5C being independently selected from H and a substituted orunsubstituted organic group, optionally wherein each R5C is H;iiib) a thiophene group, optionally having a structure selected from:each R5C being independently selected from H and a substituted or unsubstituted organic group, optionally wherein each R5C is H;iiic) a thiazole group, optionally having a structure selected from:each R5C being independently selected from H and a substituted or unsubstituted organic group, optionally wherein each R5C is H;iiid) a triazole, optionally a triazole having a structure of:R5C being selected from H and a substituted or unsubstituted organic group,optionally wherein R5C is H.

45. The PARP1 inhibitor compound according to any preceding claim, wherein when present each R5C is H or an organic group selected from a halogen, preferably F; a Cl to C3 alkyl group; a Cl to C3 haloalkyl group, optionally a fluoromethyl group such as CF2H or CF3; and a nitrile group.

46. The PARP1 inhibitor compound according to claim 45, wherein exactly one R5C is an organic group.

47. The PARP1 inhibitor compound according to claim 46, wherein the organic group is F.

48. The PARP1 inhibitor compound according to claim 44, wherein ring C has a structureselected from:

49. The PARP1 inhibitor compound according to claim 43, wherein ring C has a structurewherein:Xc° and XCm are each selected from C and N;when XCo is C, RCo is H or a halogen, F being the preferred halogen;when XCo is N, RCo is absent;when XCm is C, RCm is H or a halogen, F being the preferred halogen; and when XCm is N, RCm is absent;optionally wherein at least one of XCo and XCm is N.

50. The PARP1 inhibitor compound according to claim 49, wherein exactly one of XCo and XCm is N.

51. The PARP1 inhibitor compound according to any preceding claim, wherein R6 isselected from H, -F, -Cl, -Br, -I, -CN, -CONR51R51, -NR51COR52, -SO2NR51R51, -NR51SO2R52,-O-CR52R52R52, -CR52R52NR51R51, and any of the following structures:wherein R51 and R52 are each independently selected from H and a substituted or unsubstituted organic group, optionally wherein R51 and R52 are each independently selected from H, a halogen, optionally-deuterated Cl to C3 alkyl, and Cl to C3 haloalkyl.

52. The PARP1 inhibitor compound according to claim 51, wherein R6 is selected from -F,-Cl, -CN, -CONH2, -CONHMe (optionally -CONHCD3), -CONHEt, -CONMe2,-CONHCOMe, -CONHCH2-CH2OMe, -CONH-CH2-CH2F, -CONH-CH2-CF3, -CONH-CH2-CHF2,-OCHF2, -NHCOMe, -NHSO2Me, -SO2NHMe, -CONHSO2Me, O , O53. The PARP1 inhibitor compound according to claim 52, wherein R6 is CONHMe.54.The PARP1 inhibitor compound according to claim 53, wherein R6 is55. The PARP1 inhibitor compound according to claim 52, wherein R6 is 056. The PARP1 inhibitor compound according to claim 52, wherein R6 is Cl.

57. The PARP1 inhibitor compound according to claim 52, wherein R6 is CN.

58. The PARP1 inhibitor compound according to any preceding claim, wherein L has a structure selected from:

59. The PARP1 inhibitor compound according to any preceding claim, wherein rings D andB are in a cis configuration with respect to ring A, optionally wherein group L is selected from:

60. The PARP1 inhibitor compound according to any of claims 1 to 59, wherein rings D and B are in a trans configuration with respect to ring A, optionally wherein group L is selected from:

61. The PARP1 inhibitor compound according to claim 1, having a structure of:whereineach Z independently represents -CH2- or a heteroatom-containing fragment selected from -O- and -N(RD)-, with the proviso that no more than one Z is a heteroatomcontaining fragment;wherein RD is H or a Cl to C3 alkyl group, preferably a methyl group;XC1 and XC2 are each independently selected from C and N;when XC1 is N, R5C1 is absent;when XC1 is C, R5C1 is selected from H and a halogen;when XC2 is N, RC2 is absent;when XC2 is C, R5C2 is selected from H and a halogen;R6 is selected from -CONHMe, -Cl, and -CN.

62. The PARP1 inhibitor compound according to claim 61, wherein:when XC1 is C, R5C1 is selected from H and F; andwhen XC2 is C, R5C2 is selected from H and F.

63. The PARP1 inhibitor compound according to claim 61 or claim 62, wherein exactly one of XC1 and XC2 is N, and preferably wherein XC1 is C and XC2 is N.

64. The PARP1 inhibitor compound according to any of claims 61 to 63, wherein R6 is CONHMe, optionally -CONHCD3.

65. The PARP1 inhibitor compound according to claim 1, having a structure of:RD1 and RD2 are each independently selected from H and F;XC1 and XC2 are each independently selected from C and N;when XC1 is N, R5C1 is absent;when XC1 is C, R5C1 is selected from H and a halogen, preferably F;when XC2 is N, RC2 is absent;when X02 is C, R5C2 is selected from H and a halogen, preferably F;R6 is selected from -CONHMe, -Cl, and -CN.

66. The PARP1 inhibitor compound according to claim 65, wherein exactly one of RD1 and RD2 is F.

67. The PARP1 inhibitor compound according to claim 65 or claim 66, wherein exactly one of XC1 and XC2 is N.

68. The PARP1 inhibitor compound according to claim 67, wherein XC2 is C and XC1 is N, and optionally wherein R5C2 is H.

69. The PARP1 inhibitor compound according to claim 67, wherein XC1 is C and XC2 is N.

70. The PARP1 inhibitor compound according to claim 1, which is selected from:13trans71. The PARP1 inhibitor compound according to any of claims 1 to 60, wherein when one or more of R1, R2, R3, R5A(e.g. R5A1, R5A2, R5A3), R5B, R5C (e.g. R5C1), R6, R7, R9, R51, and R52 is a substituted or unsubstituted organic group, the or each substituted or unsubstituted organic group is independently selected from:deuterium;a halogen (such as -F, -Cl, -Br and -I);a substituted or unsubstituted linear or branched Ci-Ce alkyl group(such as Me, Et, Pr, i-Pr, n-Bu, i-Bu, t-Bu, pentyl and hexyl);a substituted or unsubstituted linear or branched Ci-Ce alkyl-aryl group(such as -CH2Ph, -CH2(2,3 or 4)F-Ph, -CH2(2,3 or 4)CI-Ph, -CH2(2,3 or 4)Br-Ph,-CH2(2,3 or4)l-Ph, -CH2CH2Ph, -CH2CH2CH2Ph,-CH2CH2CH2CH2Ph, -CH2CH2CH2CH2CH2Ph, and -CH2CH2CH2CH2CH2CH2Ph);a substituted or unsubstituted linear or branched Ci-Ce halogenated alkyl group (such as -CH2F, -CH2CI, -CH2Br, -CH2I, -CHF2, -CF3, -CCI3 -CBr3, -Cl3, -CH2CH2F, -CH2CF3, -CH2CCI3, -CH2CBr3, and -CH2CI3);NH2 or a substituted or unsubstituted linear or branched primary secondary or tertiary Ci-Ce amine group(such as -NMeH, -NMe2, -NEtH, -NEtMe, -NEt2, -NPrH, -NPrMe, -NPrEt, -NPr2, -NBuH, -NBuMe, -NBuEt, -CH2-NH2, -CH2-NMeH, -CH2-NMe2, -CH2-NEtH, -CH2-NEtMe,-CH2-NEt2, -CH2-NPrH, -CH2-NPrMe, and -CH2-NPrEt);a substituted or unsubstituted amino-aryl group(such as -NH-Ph, -NH-(2,3 or4)F-Ph, -NH-(2,3 or4)CI-Ph, -NH-(2,3 or4)Br-Ph,-NH-(2,3 or 4)I-Ph, -NH-(2,3 or 4)Me-Ph, -NH-(2,3 or 4)Et-Ph,-NH-(2,3 or4)Pr-Ph, -NH-(2,3 or4)Bu-Ph, NH-(2,3 or4)OMe-Ph,-NH-(2,3 or 4)OEt-Ph, -NH-(2,3 or 4)OPr-Ph, -NH-(2,3 or 4)OBu-Ph,-NH-2,(3,4,5 or 6)F2-Ph, -NH-2,(3,4,5 or 6)CI2-Ph, -NH-2,(3,4,5 or 6)Br2-Ph,-NH-2,(3,4,5 or 6)I2-Ph, -NH-2,(3,4,5 or 6)Me2-Ph, -NH-2,(3,4,5 or 6)Et2-Ph,-NH-2,(3,4,5, or 6)Pr2-Ph, -NH-2,(3,4,5 or 6)Bu2-Ph), a substituted or unsubstituted cyclic amine or amido group(such as pyrrolidin-l-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-l-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, 2-keto-pyrrolidinyl, 3-keto-pyrrolidinyl, 2-keto-piperidinyl, 3-keto-piperidinyl, and 4-keto-piperidinyl);a substituted or unsubstituted cyclic C3-Cs alkyl group(such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl);a substituted or unsubstituted linear or branched Ci-Ce alcohol group(such as-CH2OH, -CH2CH2OH, -CH(CH3)CH2OH, -C(CH3)2OH, -CH2CH2CH2OH, -CH2CH2CH2CH2OH, -CH(CH3)CH2CH2OH, -CH(CH3)CH(CH3)OH, -CH(CH2CH3)CH2OH, -C(CH3)2CH2OH, -ch2ch2ch2ch2ch2oh, and -CH2CH2CH2CH2CH2CH2OH);a substituted or unsubstituted linear or branched Ci-Ce carboxylic acid group(such as -COOH, -CH2COOH, -CH2CH2COOH, -CH2CH2CH2COOH, -CH2CH2CH2CH2COOH, and -CH2CH2CH2CH2CH2COOH);a substituted or unsubstituted linear or branched carbonyl group(such as -(CO)Me, -(CO)Et, -(CO)Pr, -(CO)iPr, -(CO)nBu, -(CO)iBu, -(CO)tBu, -(CO)Ph, -(CO)CH2Ph, -(CO)CH2OH, -(CO)CH2OCH3, -(CO)CH2NH2, -(CO)CH2NHMe, -(CO)CH2NMe2, -(CO)-cyclopropyl, -(CO)-l,3-epoxypropan-2-yl; -(CO)NH2, -(CO)NHMe, -(CO)NMe2,-(CO)NHEt, -(CO)NEt2,-(CO)-pyrollidine-N-yl, -(CO)-morpholine-N-yl, -(CO)-piperazine-N-yl, -(CO)-N-methyl-piperazine-N-yl, -(CO)NHCH2CH2OH, -(CO)NHCH2CH2OMe, -(CO)NHCH2CH2NH2, -(CO)NHCH2CH2NHMe, and -(CO)NHCH2CH2NMe2);a substituted or unsubstituted linear or branched Ci-Ce carboxylic acid ester group (such as -COOMe, -COOEt, -COOPr, -COO-i-Pr, -COO-n-Bu, -COO-i-Bu, -COO-t-Bu, -CH2COOMe, -CH2CH2COOMe, -CH2CH2CH2COOMe, and -CH2CH2CH2CH2COOMe);a substituted or unsubstituted linear or branched Ci-Ce amide group(such as -CO-NH2, -CO-NMeH, -CO-NMe2, -CO-NEtH, -CO-NEtMe, -CO-NEt2, -CO-NPrH, -CO-NPrMe, and -CO-NPrEt);a substituted or unsubstituted linear or branched C1-C7 amino carbonyl group (such as -NH-CO-Me, -NH-CO-Et, -NH-CO-Pr, -NH-CO-Bu, -NH-CO-pentyl, -NH-CO-hexyl, -NH-CO-Ph, -NMe-CO-Me, -NMe-CO-Et, -NMe-CO-Pr, -NMe-CO-Bu, -NMe-CO-pentyl, -NMe-CO-hexyl, -NMe-CO-Ph);a substituted or unsubstituted linear or branched C1-C7 alkoxy or aryloxy group (such as -OMe, -OEt, -OPr, -O-i-Pr, -O-n-Bu, -O-i-Bu, -O-t-Bu, -O-pentyl, -O-hexyl, -OCH2F, -OCHF2, -OCF3, -OCH2CI, -OCHCI2, -OCCI3, -O-Ph, -O-CH2-Ph,-O-CH2-(2,3 or 4)-F-Ph, -O-CH2-(2,3 or 4)-CI-Ph, -CH2OMe, -CH2OEt, -CH2OPr, -CH2OBu, -CH2CH2OMe, -CH2CH2CH2OMe, -CH2CH2CH2CH2OMe, and -CH2CH2CH2CH2CH2OMe);a substituted or unsubstituted linear or branched aminoalkoxy group(such as -OCH2NH2, -OCH2NHMe, -OCH2NMe2, -OCH2NHEt, -OCH2NEt2, -OCH2CH2NH2, -OCH2CH2NHMe, -OCH2CH2NMe2, -OCH2CH2NHEt, and -OCH2CH2NEt2);a substituted or unsubstituted sulfonyl group(such as -SO2Me, -SO2Et, -SO2Pr, -SO2iPr, -SO2Ph, -SO2-(2,3 or 4)-F-Ph,-SO2-cyclopropyl, -SO2CH2CH2OCH3, -SO2NH2, -SO2NHMe, -SO2NMe2,-SO2NHEt, -SO2NEt2, -SO2-pyrrolidine-N-yl,-SO2-morpholine-N-yl, -SO2NHCH2OMe,and -SO2NHCH2CH2OMe);a substituted or unsubstituted aminosulfonyl group(such as -NHSO2Me, -NHSO2Et, - NHSO2Pr, -NHSO2iPr, -NHSO2Ph, -NHSO2-(2,3 or4)-F-Ph, -NHSO2-cyclopropyl, -NHSO2CH2CH2OCH3);a substituted or unsubstituted aromatic group(such as Ph-, 2-F-Ph-, 3-F-Ph-, 4-F-Ph-, 2-CI-Ph-, 3-CI-Ph-, 4-CI-Ph-, 2-Br-Ph-, 3-Br-Ph-, 4-Br-Ph-, 2-l-Ph-, 3-l-Ph, 4-l-Ph-, 2,(3,4,5 or 6)-F2-Ph-, 2,(3,4,5 or 6)-CI2-Ph-, 2,(3,4,5 or 6)-Br2-Ph-, 2,(3,4,5 or 6)-l2-Ph-, 2,(3,4,5 or 6)-Me2-Ph-, 2,(3,4,5 or 6)-Et2-Ph-, 2,(3,4,5 or 6)-Pr2-Ph-,2,(3,4,5 or 6)-Bu2-Ph-, 2,(3,4,5 or 6)-(CN)2-Ph-, 2,(3,4,5 or 6)-(NO2)2-Ph-, 2,(3,4,5 or 6)-(NH2)2-Ph-, 2,(3,4,5 or 6)-(MeO)2-Ph-, 2,(3,4,5 or 6)-(CF3)2-Ph-, 3,(4 or 5)-F2-Ph-, 3,(4 or 5)-CI2-Ph-, 3,(4 or 5)-Br2-Ph-, 3,(4 or 5)-12-Ph-, 3,(4 or 5)-Me2-Ph-, 3,(4 or 5)-Et2-Ph-, 3,(4 or 5)-Pr2-Ph-, 3,(4 or 5)-Bu2-Ph-, 3,(4 or 5)-(CN)2-Ph-, 3,(4 or 5)-(NO2)2-Ph-, 3,(4 or 5)-(NH2)2-Ph-,3,(4 or 5)-(MeO)2-Ph-, 3,(4 or 5)-(CF3)2-Ph-, 2-Me-Ph-, 3-Me-Ph-, 4-Me-Ph-,2-Et-Ph-, 3-Et-Ph-, 4-Et-Ph-, 2-Pr-Ph-, 3-Pr-Ph-, 4-Pr-Ph-, 2-Bu-Ph-, 3-Bu-Ph-, 4-Bu-Ph-, 2-(CN)-Ph-, 3-(CN)-Ph-, 4-(CN)-Ph-, 2-(NO2)-Ph-, 3-(NO2)-Ph-, 4-(NO2)-Ph-, 2-(NH2)-Ph-, 3-(NH2)-Ph-, 4-(NH2)-Ph-, 2-MeO-Ph-, 3-MeO-Ph-, 4-MeO-Ph-, 2-(NH2-CO)-Ph-, 3-(NH2-CO)-Ph-, 4-(NH2-CO)-Ph-, 2-CF3-Ph-, 3-CF3-Ph-, 4-CF3-Ph-, 2-CF3O-Ph-, 3-CF3O-Ph-, and 4-CF3O-Ph-);a saturated or unsaturated, substituted or unsubstituted, heterocyclic group, optionally an aromatic heterocyclic group or a non-aromatic heterocyclic group(such as pyrrole-l-yl, pyrrole-2-yl, pyrrole-3-yl, pyrazole-l-yl, pyrazole-3-yl, pyrazole-4-yl, pyrazole-5-yl, imidazole-l-yl, imidazole-2-yl, imidazole-4-yl, imidazole-5-yl, 1,2,3-triazole-l-yl, l,2,3-triazole-4-yl, l,2,3-triazole-5-yl, 1,2,4-triazole-l-yl, l,2,4-triazole-3-yl, l,2,4-triazole-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazine-3-yl, pyridazine-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrimidin-6-yl, pyrazine-2-yl, pyrrolidine-l-yl, pyrrolidine-2-yl, pyrrolidine-3-yl, piperidine-l-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, 2-azapiperidine-l-yl, 2-azapiperidine-3-yl, 2-azapiperidine-4-yl, 3-azapiperidine-l-yl, 3-azapiperidine-2-yl, 3-azapiperidine-4-yl, 3-azapiperidine-5-yl, piperazine-l-yl, piperazine-2-yl, furan-2-yl, furan-3-yl, pyran-2-yl, pyran-3-yl, pyran-4-yl, 2-azapyran-2-yl, 2-azapyran-3-yl, 2-azapyran-4-yl, 2-azapyran-5-yl, 2-azapyran-6-yl, 3-azapyran-2-yl, 3-azapyran-4-yl, 3-azapyran-5-yl, 3-azapyran-6-yl, 4-azapyran-2-yl, 4-azapyran-3-yl, 4-azapyran-4-yl, 4-azapyran-5-yl, 4-azapyran-6-yl, oxetan-2-yl, oxetan-3-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-2-yl, 2-aza-tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-4-yl, 2-aza-tetrahydrofuran-5-yl, 3-aza-tetrahydrofuran-2-yl, 3-aza-tetrahydrofuran-3-yl, 3-aza-tetrahydrofuran-4-yl, 3-aza-tetrahydrofuran-5-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, 2-aza-tetrahydropyran-2-yl, 2-aza-tetrahydropyran-3-yl, 2-aza-tetrahydropyran-4-yl, 2-aza-tetrahydropyran-5-yl, 2-aza-tetrahydropyran-6-yl, 3-aza-tetrahydropyran-2-yl, 3-aza-tetrahydropyran-3-yl, 3-aza-tetrahydropyran-4-yl, 3-aza-tetrahydropyran-5-yl, 3-aza-tetrahydropyran-6-yl, morpholine-2-yl, morpholine-3-yl, morpholine-4-yl, thiophen-2-yl, thiophen-3-yl, isothiazole-3-yl, isothiazole-4-yl, isothiazole-5-yl, thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, thiopyran-2-yl, thiopyran-3-yl, thiopyran-4-yl, 2-azathiopyran-2-yl, 2-azathiopyran-3-yl, 2-azathiopyran-4-yl, 2-azathiopyran-5-yl, 2-azathiopyran-6-yl, 3-azathiopyran-2-yl, 3-azathiopyran-4-yl,3-azathiopyran-5-yl, 3-azathiopyran-6-yl, 4-azathiopyran-2-yl, 4-azathiopyran-3-yl, 4-azathiopyran-4-yl, 4-azathiopyran-5-yl, 4-azathiopyran-6-yl, thiolane-2-yl, thiolane-3-yl, thiane-2-yl, thiane-3-yl, thiane-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, furazan-3-yl, (l,3,4-oxadiazol)-2-yl, (l,3,4-oxadiazol)-5-yl, (l,2,4-oxadiazol)-3-yl, (l,2,4-oxadiazol)-5-yl; and tetrazole-l-yl, tetrazole-2-yl, tetrazole-5-yl);wherein:a pair of R5A groups attached to different atoms may together form a ring with ring A atoms; and / ora pair of R5B groups attached to different atoms may together form a ring with ring B atoms, and / ora pair of R5C groups attached to different atoms may together form a ring with ring C atoms; and / oran R5C group and an R6 group attached to different atoms may together form a ring with ring C atoms.

72. The PARP1 inhibitor compound according to claim 71, wherein each of R5A (e.g., R5A1, rsa2, r5A3), r5b, anc| r5c (e g , r5cij js independently absent or selected from:H,deuterium,a halogen, such as -F, -Cl, -Br, and -I; preferably F or Cl;a nitrile group;a Ci-Ce alkyl group;a Ci-C6 halogenated alkyl group, preferably CF3 or CHFz;a cyclopropyl group;an -OH group;a Ci-Ce alcohol group;a C1-C7 amino carbonyl group, such as -NH-CO-Me;an -NH2 group;a Ci-Ce amino group; andwherein, when a pair of R5A groups attached to different atoms together forms a ring with ring A atoms and / or a pair of R5B groups attached to different atoms together forms a ring with ring B atoms and / or a pair R5C groups attached to different atoms together forms a ring with ring C atoms, each of the pair of R5A, R5B or R5C groups independently comprises -CH2- or -CH2CH2-, or the pair of groups together comprise -CH=CH-CH=CH- or -NH-CO-NH-.

73. The PARP1 inhibitor compound according to any preceding claim, which is in the form of:an isolated enantiomer, ora mixture of two or more enantiomers, ora mixture of two or more diastereomers, and / or epimers, ora racemic mixture, ora tautomer of the compound.

74. The PARP1 inhibitor compound according to any preceding claim, which is selective for PARP1 over PARP2.

75. The PARP1 inhibitor compound of any preceding claim, for use in medicine.

76. The PARP1 inhibitor compound for use according to claim 75, which is for use intreating a cancer.

77. The PARP1 inhibitor compound for use according to claim 76, wherein the cancer is selected from: a cancer of the eye; brain, such as gliomas, glioblastomas, medulloblastomas, craniopharyngioma, ependymoma, and astrocytoma; spinal cord; kidney; mouth; lip; throat; oral cavity; nasal cavity; small intestine; colon; parathyroid gland; gall bladder; head and neck; breast; bone; bile duct; cervix; heart; hypopharyngeal gland; lung; bronchus; liver; skin; ureter; urethra; testicles; vagina; anus; laryngeal gland; ovary; thyroid; oesophagus; nasopharyngeal gland; pituitary gland; salivary gland; prostate; pancreas; adrenal glands; an endometrial cancer; oral cancer; melanoma; neuroblastoma; gastric cancer; an angiomatosis; a hemangioblastoma; a pheochromocytoma; a pancreatic cyst; a renal cell carcinoma; Wilms' tumour; squamous cell carcinoma; sarcoma; osteosarcoma; Kaposi sarcoma;rhabdomyosarcoma; hepatocellular carcinoma; PTEN Hamartoma-Tumor Syndromes, such as Lhermitte-Duclos disease, Cowden syndrome, Proteus syndrome, and Proteus-like syndrome; leukaemias and lymphomas, such as acute lymphoblastic leukaemia, chronic lymphocytic leukaemia, acute myelogenous leukaemia, chronic myelogenous leukaemia, hairy cell leukaemia, T-cell prolymphocytic leukaemia, large granular lymphocytic leukaemia, adult T-cell leukaemia, juvenile myelomonocytic leukaemia, Hodgkin lymphoma, non-Hodgkin lymphoma, mantle lymphoma, follicular lymphoma, primary effusion lymphoma, AIDS-related lymphoma, diffuse B cell lymphoma, Burkitt lymphoma, cutaneous T-cell lymphoma, nasopharyngeal and gastrointestinal cancers;optionally wherein the cancer is a cancer of the brain or spinal cord.

78. The PARP1 inhibitor compound for use according to claim 76 or claim 77, wherein the cancer is deficient in a DNA damage response repair pathway, such as Homologous Recombination dependent DNA Double Strand Break DNA repair activity.

79. The PARP1 inhibitor compound for use according to any of claims 76 to 78, wherein the cancer is deficient in BRCA1 and / or BRCA2 function.

80. The PARP1 inhibitor compound for use according to any of claims 76 to 79, which is to be administered in conjunction with a further agent for treating cancer; optionally wherein the further agent for treating cancer is selected from anti-microtubule agents, platinum coordination complexes, alkylating agents, antibiotic agents, topoisomerase I inhibitors, topoisomerase II inhibitors, antimetabolites, senolytic agents, hormones and hormone analogues, signal transduction pathway inhibitors, other DNA damage repair pathway inhibitors, non-receptor tyrosine kinase angiogenesis inhibitors, antibody-drug conjugates, immunotherapeutic agents, hormone deprivation therapy, proapoptotic agents, radioligand therapies, cell cycle signalling inhibitors, and anti-angiogenic agents.

81. The PARP1 inhibitor compound for use according to claim 80, wherein the further agent is an immunotherapeutic agent selected from: an anti-tumour vaccine; an oncolytic virus; an immune stimulatory antibody such as anti-CTLA4, anti-PDl, anti-PDL-1, anti-OX40, anti-41BB, anti-CD27, anti-CD40, anti-LAG3, anti-TIM3, and anti-GITR; a pattern recognition receptoragonist such as a STING, TLR-9 or RIG-1 Helicase agonist; an IDO or TDO inhibitor; a novel adjuvant; a peptide; a cytokine; a chimeric antigen receptor T cell therapy; a small molecule immune modulator; and a tumour microenvironment modulator.

82. A pharmaceutical composition comprising a PARP1 inhibitor compound as defined in any of claims 1 to 74.

83. A pharmaceutical composition according to claim 82, further comprising a pharmaceutically acceptable additive and / or excipient, and / or wherein the compound is in the form of a pharmaceutically acceptable salt, hydrate, acid, ester, or other alternative form of the compound.

84. The pharmaceutical composition according to claim 82 or claim 83, further comprising a further agent for treating cancer; optionally wherein the further agent for treating cancer is selected from anti-microtubule agents, platinum coordination complexes, alkylating agents, antibiotic agents, topoisomerase I inhibitors, topoisomerase II inhibitors, antimetabolites, senolytic agents, hormones and hormone analogues, signal transduction pathway inhibitors, other DNA damage repair pathway inhibitors, non-receptor tyrosine kinase angiogenesis inhibitors, antibody-drug conjugates, immunotherapeutic agents, hormone deprivation therapy, proapoptotic agents, radioligand therapies, anti-angiogenic agents, and cell cycle signalling inhibitors.

85. The pharmaceutical composition according to claim 84, wherein the further agent comprises an immunotherapeutic agent selected from: an anti-tumour vaccine; an oncolytic virus; an immune stimulatory antibody such as anti-CTLA4, anti-PDl, anti-PDL-1, anti-OX40, anti-41BB, anti-CD27, anti-CD40, anti-LAG3, anti-TIM3, and anti-GITR; a pattern recognition receptor agonist such as a STING, TLR-9 or RIG-1 Helicase agonist; an IDO or TDO inhibitor; a novel adjuvant; a peptide; a cytokine; a chimeric antigen receptor T cell therapy; a small molecule immune modulator; and a tumour microenvironment modulator.

86. The pharmaceutical composition according to any of claims 82 to 85, for use in treatinga cancer.

87. A pharmaceutical kit for treating a cancer, which pharmaceutical kit comprises:a) a PARP1 inhibitor compound as defined in any of claims 1 to 74; and b) a further agent for treating cancer;wherein the PARP1 inhibitor compound and the further agent are suitable for administration simultaneously, sequentially or separately; andoptionally wherein the further agent for treating cancer is selected from anti-microtubule agents, platinum coordination complexes, alkylating agents, antibiotic agents, topoisomerase I inhibitors, topoisomerase II inhibitors, antimetabolites, senolytic agents, hormones and hormone analogues, signal transduction pathway inhibitors, other DNA damage repair pathway inhibitors, non-receptor tyrosine kinase angiogenesis inhibitors, antibody-drug conjugates, hormone-deprivation therapy, immunotherapeutic agents (such as selected from an anti-tumour vaccine; an oncolytic virus; an immune stimulatory antibody such as anti-CTLA4, anti-PDl, anti-PDL-1, anti-OX40, anti-41BB, anti-CD27, anti-CD40, anti-LAG3, anti-TIM3, and anti-GITR; a pattern recognition receptor agonist such as a STING, TLR-9 or RIG-1 Helicase agonist; an IDO orTDO inhibitor; a novel adjuvant; a peptide; a cytokine; a chimeric antigen receptor T cell therapy; a small molecule immune modulator; a tumour microenvironment modulator), proapoptotic agents, radioligand therapies, anti-angiogenic agents, and cell cycle signalling inhibitors.

88. A method of treating a disease and / or a condition and / or a disorder, which method comprises administering to a patient a PARP1 inhibitor compound, a composition or a kit as defined in any preceding claim.

89. The method according to claim 88, wherein the patient is an animal, preferably a mammal, optionally a human, canine, equine or feline; and preferably a human.

90. A method of synthesising a PARP1 inhibitor compound as defined in any of claims 1 to 74, which method comprises conducting a reaction between:i) a first reactant comprising rings D and E and bearing a first portion of group Land ii) a second reactant comprising a remainder of group L,to form the PARP1 inhibitor compound.

91. The method according to claim 90, wherein the first reactant comprises rings D, E and ring A, and the second reactant comprises a ring B precursor bearing a reactive group, which method comprises joining ring A to the ring B precursor.

92. The method according to claim 91, wherein the reactive group precursor comprises a carbonyl group, an alkyl halide, or an alkyl sulfonate.

93. The method according to any of claims 90 to 92, wherein the reaction comprises alkylation, reductive amination or amide formation so as to form group L.

94. The method according to claim 90, wherein the first reactant comprises rings D, E, ring A, and ring B, and the second reactant comprises a ring C derivative bearing a leaving group such as a halide or sulfonate.

95. The method according to claim 94, wherein the reaction comprises a nucleophilic substitution reaction, such as a nucleophilic aromatic substitution reaction, so as to form group L.

96. The method according to any of claims 90 to 95, further comprising separating structural isomers of the PARP1 inhibitor compound using chiral supercritical fluid chromatography and / or chiral high-performance liquid chromatography.

Images