6-aminopurine derivatives useful as POLQ inhibitors

Abstract

The specification generally relates to compounds of Formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, wherein G, Ga, Gb, X, Y, R1, R2, Q1, Q2, and Q3 have any of the meanings defined herein, together with compositions containing them and their use in therapy. The compounds are inhibitors of the polymerase, DNA polymerase theta (Polθ or POLQ), and are thereby particularly useful in the treatment of cancer.

Description

[0001] POLQ INHIBITORS BACKGROUND DNA polymerase theta (Polθ) is a specialized polymerase encoded in the human genome 5 by the POLQ gene and hence it is also simply known as POLQ. It belongs to the A family, a group of DNA polymerases regarded as error prone due to their lack of proofreading activity. It is the only human DNA polymerase that also contains an active DNA helicase domain (Loeb and Monnat, 2008; Ramsden et al., 2022). POLQ has been involved in genome maintenance processes through its roles in translesion synthesis (TLS), a DNA-damage tolerance mechanism, and 10 alternative DNA-end joining (alt-EJ), a DNA repair mechanism involved in the resolution of DNA double-strand breaks (DSBs) (Ramsden et al., 2022; Yoon et al., 2019). DNA DSBs are the most cytotoxic lesion faced by cells and several DNA-damage signalling and repair mechanisms have evolved to deal with them. In human cells, DSB repair is mostly performed by the non-homologous end joining (NHEJ) and homologous recombination 15 repair (HRR) pathways, with a third pathway, named alt-EJ, generally regarded as a less frequently used option. The first steps of the HRR and alt-EJ pathways are shared, where the ends of the DNA DSB will be processed (resected) to generate regions of single-stranded DNA (ssDNA). While during HRR resection is relatively extensive, it is kept to shorter stretches during alt-EJ through a mechanism that remained elusive. In addition, alt-EJ has been linked to the use of sequence 20 microhomologies (2-6 base pairs) surrounding the DSB site for repair by direct annealing, processing of the DNA flaps and ligation, which explains its error-prone nature. As such, alt-EJ is also referred to as microhomology-mediated end joining (MMEJ) (Ciccia and Elledge, 2010). HRR is a form of DNA repair that, once a DSB has occurred on a chromosome’s chromatid, uses the sister chromatid as template for repair. As such, HRR is regarded as error-free and can 25 only take place once a sister chromatid is available, namely during the DNA replication (synthesis) phase (S phase) and gap phase 2 (G2 phase) of the cell cycle. HRR deficiency (HRD) is well described in tumours and is genetically associated with mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 (BRCA genes), among others (Pellegrino et al., 2019). HRD is also associated with increasing levels of genomic instability, highlighted by the presence of specific mutational signatures involving single-base substitutions (SBS), insertions-deletions (INDEL) and rearrangements (Nik-Zainal et al., 2016). Interestingly, the SBS signature associated with HRD (SBS3), is also associated with an INDEL signature (ID6) that is characterised by extensive microhomology usage at the break point (Alexandrov et al., 2020), suggesting that MMEJ could 5 be an important DNA repair pathway in the absence of HRR. In agreement with this, signatures of MMEJ-mediated repair events have been identified in secondary (reversion) mutations restoring the open-reading frame of BRCA and other HRR-related genes in tumours from patients progressing on treatment, strongly suggesting that these reversion events are mediated by MMEJ repair and driving therapy resistance in these clinical cases (Pettitt et al., 2020; Tobalina et al., 10 2021). Recently, POLQ has been involved in MMEJ repair while not playing a significant role in HRR, making it the only MMEJ-specific protein known to date (Wyatt et al., 2016; Yousefzadeh et al., 2014). Interestingly, reports have highlighted a synthetic lethal genetic dependency between inactivating mutations in genes involved in HRR (BRCA1, BRCA2, FANCD2, ATM) and lack of 15 POLQ activity (Ceccaldi et al., 2015; Mateos-Gomez et al., 2015; Shima et al., 2004), being that activity either polymerase or helicase (Mateos-Gomez et al., 2017). As such, there is an increasing interest in developing POLQ inhibitors for the treatment of HRD tumours, both as single agents or in combination with poly(ADP-ribose) polymerase (PARP) inhibitors (Zatreanu et al., 2021; Zhou et al., 2021). Importantly, it has also been shown that POLQ-deficient cells are sensitive to 20 DNA damaging agents including ionising radiation (Higgins et al., 2010; Yousefzadeh et al., 2014), which could open the possibility of combinations of POLQ inhibitors with chemo- or radiotherapy (Higgins and Boulton, 2018). Accordingly, there is a need for POLQ inhibitors that are selective, demonstrate good bioavailability and are suitable for dosing. 25 SUMMARY The present specification provides a compound of formula (I):

[0002] or a stereoisomer ; wherein, R1and R2are each, independently, H, halo, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3hydroxyalkyl, -CN, C2-C4 alkynyl, or C2-C6 alkoxyalkyl; Q1, Q2, and Q3are, independently N, C-L-R, or CRx, wherein one and only one of Q1, Q2, and Q3is C-L-R; L is -O-; -C(O)-; -O(CH2)qC(O)-; -C(O)NRy-; -O(CH2)qC(O)NRy-; -O(CH2)qNRy; -NRy-; - (CH2)q-; -(CH2)qNRy-; -(CH2)qO-; -(CH2)qC(O)-; -(CH2)qC(O)O-; or -O(CH2)q-; q is, independently, 1, 2, or 3 R is H, Ra, Rb, Rc, or Rd; Rais a 3-10 membered heterocycle optionally substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, -CN, -S(O)2OH, C1-C4 alkylamino, C1-C5 alkoxy, C2-C5alkoxyalkyl, 4-6 membered heterocycle, C1-C7alkyl, -S(O)2C1-C3alkyl and - C(O)-C3-C6 carbocycle, wherein the C1-C7 alkyl is optionally substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, -CN, C2-C8 ester, and C1-C5 alkoxy; Rbis a C1-C7 alkyl, wherein one or two methylene groups from the C1-C7 alkyl are optionally independently replaced with NRe, O, S, S(O) or CW1W2wherein W1and W2together form a C3- C6carbocycle, and one or two single bonds in a C2-C7alkyl chain are optionally independently replaced with a double or triple bond(s), wherein the C1-C7 alkyl is optionally substituted with 1 to 4 substituents independently selected from: halo, oxo, hydroxy, carboxy, amino, -CN, C2-C4alkynyl, C2-C6carbamate, C1-C8 amide, C1-C4 sulfonyl, C1-C4 sulfonamide, C1-C4 alkylamino, C1-C5 alkoxy, C3-C6 carbocycle, and 3-10 membered heterocycle, wherein the C3-C6carbocycle is optionally substituted with 1 to 4 substituents independently selected from hydroxy, halo, and carboxy; wherein the 3-10 membered heterocycle is optionally substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, - CN, -S(O)2OH, C1-C4alkylamino, C1-C5alkoxy, C2-C5alkoxyalkyl, 4-6 membered heterocycle, and C1-C7 alkyl, wherein the C1-C7 alkyl is optionally substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, -CN, C2-C8ester, and C1-C5alkoxy; Rcis a C3-C6 carbocycle optionally substituted with 1 to 4 substituents independently selected from hydroxy halo, carboxy, C1-C3 alkyl, and CN; Rdis C1-C4sulfonyl or C1-C4sulfonamide; Ryis H, C1-C3 alkyl, or C1-C3 haloalkyl; Rxis H, halo, hydroxy, -CN, -NH2, C1-C3 alkoxy, C1-C3 alkyl, or C1-C3 haloalkyl; Reis H, halo, C1-C8 alkyl, or C1-C8 haloalkyl; X is a C1-C4alkylene; Y is a phenyl or 5-6 membered heteroaryl, wherein the phenyl or 5-6 membered heteroaryl is optionally substituted with 1 to 3 substituents independently selected from halo, C1-C3 alkyl, C1- C3alkoxy, -CN, C1-C3haloalkyl, and cyclopropyl; G is N or CH; Ga and Gb are N, CH, or CR5wherein one, and only one, of Ga and Gb is N or CH and one, and only one, of Gaand Gbis CR5; , Rzis H, C1-C3alkyl, or Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4- 6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, and: when Rzis H or C1-C3alkyl: (i) Zaand Zbare, independently, H, C1-C5 alkyl, or halo, wherein the C1-C5 alkyl is optionally substituted with hydroxy, or Zaand Zbtogether form a saturated C3- C6 carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3alkoxy, and C1-C3alkyl optionally substituted with hydroxy, or Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, C1-C3 alkyl, halo, hydroxy, C1-C3 alkoxy, C2-C5 alkoxyalkyl, C3-C6 carbocycle, 5-6 membered heteroaryl, or phenyl, wherein the C1-C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide, or (ii) Za, Zband Zctogether form a 5-membered bicyclic ring system containing a bridge of 1 carbon atom; when Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl: Zband Zcare, independently, H, C1-C3alkyl, or C3-C6carbocycle, or Zband Zctogether form a C3-C6 carbocycle or a 4-6 membered heterocycle, or Zbtogether with Rzand Zaform a 7-membered heterobicyclic ring system containing a bridge of 2 carbon atoms, and Zcis H. In some embodiments, the present specification provides a compound of formula (I), wherein: R1and R2are each, independently, H or halo; Q1and Q3are each, independently, CH; Q2is C-L-Rbwherein L is O; Rbis a C1-C7 alkyl, wherein one or two methylene groups from the C1-C7 alkyl is optionally independently replaced with NRe, and wherein the C1-C7alkyl is optionally substituted with carboxy or 3-10 membered heterocycle, Reis C1-C8 alkyl; X is a C1-C4alkylene; Y is a phenyl or 5-6 membered heteroaryl, wherein the phenyl or 5-6 membered heteroaryl is optionally substituted with 1 to 3 substituents independently selected from halo and C1-C3 alkyl; G is N or CH; Gb is N; Ga is CR5; ; Rzis H, C1-C3alkyl, or Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4- 6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, and: when Rzis H or C1-C3alkyl: (i) Zaand Zbare, independently, H, C1-C5 alkyl, or halo, wherein the C1-C5 alkyl is optionally substituted with hydroxy, or Zaand Zbtogether form a saturated C3- C6 carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3 alkoxy, and C1-C3 alkyl optionally substituted with hydroxy, or Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, C1-C3 alkyl, halo, hydroxy, C1-C3 alkoxy, C2-C5 alkoxyalkyl, C3-C6 carbocycle, 5-6 membered heteroaryl, or phenyl, wherein the C1-C3alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide, or (ii) Za, Zband Zctogether form a 5-membered bicyclic ring system containing a bridge of 1 carbon atom; when Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl: Zband Zcare, independently, H, C1-C3 alkyl, or C3-C6 carbocycle, or Zband Zctogether form a C3-C6 carbocycle or a 4-6 membered heterocycle, or Zbtogether with Rzand Zaform a 7-membered heterobicyclic ring system containing a bridge of 2 carbon atoms, and Zcis H. The present specification also provides a pharmaceutical composition which comprises a compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as described anywhere herein, and at least one pharmaceutically acceptable excipient. The present specification also provides a compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as described anywhere herein, or a pharmaceutical composition thereof, for use in the treatment cancer. In some embodiments, the cancer is breast, ovarian, pancreatic, or prostate cancer. The present specification also provides a method of treating cancer which comprises administering to a patient in need thereof, a therapeutically effective amount of a compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as described anywhere herein or of a pharmaceutical composition thereof. In some embodiments, the cancer is breast, 5 ovarian, pancreatic, or prostate cancer. The present specification also provides the use of a compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as described anywhere, or a pharmaceutical composition thereof, in the manufacture of a medicament for the treatment of cancer in a subject. In some embodiments, the cancer is breast, ovarian, pancreatic, or prostate 10 cancer. DETAILED DESCRIPTION This detailed description and its specific examples, while indicating embodiments, are intended for purposes of illustration only. Therefore, there is no limitation to the illustrative 15 embodiments described in this specification. In addition, it is to be appreciated that various features that are, for clarity reasons, described in the context of separate embodiments, also may be combined to form a single embodiment. Conversely, various features that are, for brevity reasons, described in the context of a single embodiment, also may be combined to form sub-combinations thereof. 20 Listed below are definitions of various terms used in the specification and claims. The term “alkoxy” refers to an alkyl group attached to the rest of the molecule via an oxygen atom. Representative alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, tert-butoxy and the like. The term “alkoxyalkyl” refers to an alkyl group attached to an alkoxy group, where in the 25 group is attached to the rest of the molecule via a carbon on the alkyl group, i.e. a group having a structure of -Rʹ-O-Rʹʹ wherein Rʹ and Rʹʹ are the same or different alkyl groups. The term “alkyl” refers to a straight chained or branched non-aromatic hydrocarbon which is completely saturated. The term “alkylene” refers to a saturated hydrocarbon group with two points of attachment to adjacent atoms / groups. Alkyls and alkylenes may include straight chain(s) and / or branched c hain(s). Examples of straight chained and branched alkyl groups include methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, pentyl and octyl. The term “alkylamino” refers to an amino group substituted with at least one alkyl group, i.e. a group having a structure of -NRʹRʹʹ, NHRʹ, NRʹʹRʹH+, or NH2Rʹ+ wherein Rʹ and Rʹʹ are the 5 same or different alkyl groups. The term “alkynyl” is a non-aromatic hydrocarbon comprising at least one carbon-carbon triple bond. Examples of alkynyl groups include acetylenyl, propynyl, and butynyl. The term “amide” refers to a group with the general formula of RʹC(=O)NRʹʹRʹʹʹ, or are either hydrogen, the same or different alkyl groups, 10 The amide is connected to the rest of the molecule via either the or the nitrogen. The term “amino” refers to a group with the formula -NRʹRʹʹ wherein Rʹ and Rʹʹ are independently selected from, for example, hydrogen or a hydrocarbon group, or, in the case of a “cyclic” amino group, Rʹ and Rʹʹ, taken together with the nitrogen atom to which they are attached, 15 form a heterocyclic ring. Amino groups may be primary (-NH2), secondary (-NHRʹ where Rʹ is a hydrocarbon group), or tertiary (-NRʹRʹʹ where Rʹ and Rʹʹ are both independently selected from hydrocarbon groups). In cationic form, amino groups may be quaternary. The term “carbamate” refers to a group with the general formula of RʹOC(O)NRʹʹRʹʹʹ or wherein Rʹ, Rʹʹ, and Rʹʹʹ are either hydrogen or the same or different alkyl 20 least one is an alkyl group. The carbamate is connected to the rest of the molecule via the oxygen or the nitrogen or a carbon on any of the alkyl groups. The term “carbocycle” refers to a partially or completely saturated non-aromatic hydrocarbon ring system, including cycloalkyls, cycloalkenyls, and cycloalkynyls. Cycloalkyls include cyclopropane, cyclobutane, cyclopentane, cyclohexane, cyclopropene, cyclobutene, cyclopentene, and cyclohexene. In some embodiments, the carbocycle is a saturated carbocycle. Carbocycles include monocyclic carbocycles as well as spiro, fused and / or bridged polycyclic carbocycles such as bicyclic carbocycles. Examples of polycyclic carbocycles include 5 bicyclo[1.1.1]pentane. The term “carboxy” refers to a group with the formula -C(=O)OH. The term “ester” refers to a group having the structure Rʹ-C(O)-ORʹʹ, or wherein Rʹ and Rʹʹ are the same or different alkyl groups. The ester is of the molecule via a carbon on either alkyl group. 10 The term “halo” means fluoro, chloro, bromo, and iodo. In some embodiments, halo is fluoro or chloro. In other embodiments, halo is fluoro. In still other embodiments, halo is chloro. The term “haloalkyl” means an alkyl group in which one or more hydrogens has been substituted with a halo. The term “heteroaryl” refers to a substituted or unsubstituted monocyclic aromatic ring 15 system, whose ring structures include at least one heteroatom. Examples of monocyclic heteroaryls or heteroarylenes include, but are not limited to, pyrrole, pyridine, pyrazine, pyridazine, pyrimidine, furan, triazole, thiophene, imidazole, isoxazole, oxazole, oxadiazole, thiazole and pyrazole. The term “hydroxyalkyl” means an alkyl group in which one or more hydrogens has been 20 substituted with a hydroxy group. The term “heterocycle” refers to a partially or completely saturated hydrocarbon ring system wherein at least one of the ring carbon atoms is replaced with a heteroatom independently selected from nitrogen, oxygen and sulphur. Heterocyclic groups can be attached to the rest of the molecule via a carbon or nitrogen ring-member atoms. Heterocycles include monocyclic 25 heterocycles as well as spiro, fused and / or bridged polycyclic heterocycles such as bicyclic heterocycles. In certain embodiments, the heterocycle is a saturated heterocycle. Examples of monocyclic heterocycles include, but are not limited to, tetrahydropyran, tetrahydrofuran, morpholine, azetidine, pyrrolidine, piperidine, piperazine, pyridine, azepane, diazepane, oxetane, tetrahydropyran, thietane, and isoxazolidine. Examples of polycyclic heterocycles include 5- azabicyclo[2.2.1]heptane, 4-azaspiro[2.4]heptane, 1-azaspiro[3.3]heptane, 5-azaspiro[3.4]octane, 2-oxa-5-azaspiro[3.4]octane, 5-azaspiro[2.4]heptane, and 6-oxa-1-azaspiro[3.3]heptane. The term “sulfonamide” refers to a group with the formula -S(=O)2NRʹRʹʹ, wherein Rʹ and Rʹʹ are independently amino substituents, as defined for amino groups. The term “sulfonyl” refers to a group having the general formula RʹS(O)2Rʹʹ, or wherein Rʹ and Rʹʹ are either hydrogen or the same or different alkyl groups, provided at least one is an alkyl group. The sulfonyl is connected to the rest of the molecule via the sulfur or a carbon on either alkyl group. In this specification the prefix Cx-y as used in terms such as “Cx-y alkyl” and the like where x and y are integers, indicates the numerical range of carbon atoms that are present in the group. Examples of suitable C1-3 alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, and i-propyl. Examples of suitable C1-4alkyl groups include, but are not limited to, methyl, ethyl, n- propyl, and i-propyl, n-butyl, i-butyl, s-butyl and t-butyl. In some cases, a group will have two sections comprising carbon, in which case the prefix indicates the numerical range of total carbons in the group, e.g., C2-6alkoxyalkyl, refers to an alkoxyalkyl group wherein the alkyl group and the alkoxy group together have 2 to 6 carbons. A “patient” or “subject” refers to an animal in which the one or more active agents as described herein will have a therapeutic effect. In some embodiments, the patient is a human being. As used herein, unless otherwise stated, the term “pharmaceutically acceptable” as used herein refers to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio. As used herein, unless otherwise stated, the phrase "effective amount" means an amount of a compound or composition which is sufficient to significantly and positively modify the symptoms and / or conditions to be treated (e.g., provide a positive clinical response). The effective amount of an active ingredient for use in a pharmaceutical composition will vary with the particular condition being treated, the severity of the condition, the duration of the treatment, the nature of concurrent therapy, the particular active ingredient(s) being employed, the particular 5 pharmaceutically-acceptable excipient(s) / carrier(s) utilized, and like factors within the knowledge and expertise of the attending physician. The term "treating", as used herein, unless otherwise indicated, means reversing, alleviating, inhibiting the progress of, or slowing or delaying the progression of, the disorder or condition to which such term applies, or one or more symptoms of such disorder or condition. The 10 term "treatment", as used herein, unless otherwise indicated, refers to the act of treating as "treating" is defined immediately above. The term "treating" also includes adjuvant and neo- adjuvant treatment of a subject. The term "treating" also includes the reduction or inhibition of the growth of a tumor or proliferation of cancerous cells in a subject. The language “pharmaceutically acceptable salt” includes acid addition or base addition 15 salts that retain the biological effectiveness and properties of the compounds disclosed herein. In many cases, the compounds disclosed herein capable of forming acid and / or base salts by virtue of the presence of basic and / or carboxyl groups or groups similar thereto. Compounds 20 The present specification provides a compound of formula (I): or a stereoisomer wherein, R1and R2are each, independently, H, halo, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3hydroxyalkyl, -CN, C2-C4 alkynyl, or C2-C6 alkoxyalkyl; Q1, Q2, and Q3are, independently N, C-L-R, or CRx, wherein one and only one of Q1, Q2, and Q3is C-L-R; L is -O-; -C(O)-; -O(CH2)qC(O)-; -C(O)NRy-; -O(CH2)qC(O)NRy-; -O(CH2)qNRy; -NRy-; - (CH2)q-; -(CH2)qNRy-; -(CH2)qO-; -(CH2)qC(O)-; -(CH2)qC(O)O-; or -O(CH2)q-; p is, independently, 1, 2, or 3 R is H, Ra, Rb, Rc, or Rd; Rais a 3-10 membered heterocycle optionally substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, -CN, -S(O)2OH, C1-C4 alkylamino, C1-C5 alkoxy, C2-C5alkoxyalkyl, 4-6 membered heterocycle, C1-C7alkyl, S(O)2C1-C3alkyl and -C(O)- C3-C6 carbocycle, wherein the C1-C7 alkyl is optionally substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, -CN, C2-C8 ester, and C1-C5 alkoxy; Rbis a C1-C7 alkyl, wherein one or two methylene groups from the C1-C7 alkyl are optionally independently replaced with NRe, O, S, S(O), or CW1W2wherein W1and W2together form a C3-C6 carbocycle, and one or two single bonds in a C2-C7 alkyl chain are optionally independently replaced with a double or triple bond(s), wherein the C1-C7 alkyl is optionally substituted with 1 to 4 substituents independently selected from: halo, oxo, hydroxy, carboxy, amino, -CN, C2-C4 alkynyl, C2-C6 carbamate, C1-C8amide, C1-C4sulfonyl, C1-C4sulfonamide, C1-C4alkylamino, C1-C5alkoxy, C3-C6carbocycle, and 3-10 membered heterocycle, wherein the C3-C6 carbocycle is optionally substituted with 1 to 4 substituents independently selected from hydroxy, halo, and carboxy; wherein the 3-10 membered heterocycle is optionally substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, - CN, -S(O)2OH, C1-C4 alkylamino, C1-C5 alkoxy, C2-C5 alkoxyalkyl, 4-6 membered heterocycle, and C1-C7alkyl, wherein the C1-C7alkyl is optionally substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, -CN, C2-C8 ester, and C1-C5 alkoxy; Rcis a C3-C6carbocycle optionally substituted with 1 to 4 substituents independently selected from hydroxy halo, carboxy, C1-C3 alkyl, and CN; Rdis C1-C4 sulfonyl or C1-C4 sulfonamide; Ryis H, C1-C3alkyl, or C1-C3haloalkyl; Rxis H, halo, hydroxy, -CN, -NH2, C1-C3alkoxy, C1-C3alkyl, or C1-C3haloalkyl; Reis H, halo, C1-C8 alkyl, or C1-C8 haloalkyl; X is a C1-C4 alkylene; Y is a phenyl or 5-6 membered heteroaryl, wherein the phenyl or 5-6 membered heteroaryl is optionally substituted with 1 to 3 substituents independently selected from halo, C1-C3 alkyl, C1- C3 alkoxy, -CN, C1-C3 haloalkyl, and cyclopropyl; G is N or CH; Ga and Gb are N, CH, or CR5wherein one, and only one, of Ga and Gb is N or CH and one, and only one, of Ga and Gb is CR5; ; Rzis H, C1-C3 alkyl, or Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4- 6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, and: when Rzis H or C1-C3alkyl: (i) Zaand Zbare, independently, H, C1-C5 alkyl, or halo, wherein the C1-C5 alkyl is optionally substituted with hydroxy, or Zaand Zbtogether form a saturated C3- C6 carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3 alkoxy, and C1-C3 alkyl optionally substituted with hydroxy, or Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, C1-C3 alkyl, halo, hydroxy, C1-C3 alkoxy, C2-C5 alkoxyalkyl, C3-C6 carbocycle, 5-6 membered heteroaryl, or phenyl, wherein the C1-C3alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide, or (ii) Za, Zband Zctogether form a 5-membered bicyclic ring system containing a bridge of 1 carbon atom; when Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl: Zband Zcare, independently, H, C1-C3 alkyl, or C3-C6 carbocycle, or Zband Zctogether form a C3-C6 carbocycle or a 4-6 membered heterocycle, or Zbtogether with Rzand Zaform a 7-membered heterobicyclic ring system containing a bridge of 2 carbon atoms, and Zcis H. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein R1and R2are each, independently, H, halo, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 hydroxyalkyl, -CN, or C2-C4 alkynyl. In some embodiments R1and R2are each, independently, H, halo, -CH3, -OCH3, CH2OH, -CN, or -C-CH. In some embodiments R1and R2are each, independently, H, halo, or C1-C3 alkyl. In some embodiments R1and R2are each, independently, H, halo, or -CH3. In some embodiments R1and R2are each, independently, H, Cl, F, or -CH3. In some embodiments R1and R2are H. In some embodiments R1is H. In some embodiments R1is -CH3. In some embodiments R1is halo. In some embodiments R1is Cl. In some embodiments R1is F. In some embodiments R2is H. In some embodiments R2is -CH3. In some embodiments R2is halo. In some embodiments R2is Cl. In some embodiments R2is F. In some embodiments R1is -CH3and R2is H. In some embodiments R1is H and R2is - CH3. In some embodiments R1and R2are each, independently, H or halo. In some embodiments R1and R2are each, independently, H, Cl, or F. In some embodiments R1or R2is halo and the other is H. In some embodiments R1or R2is Cl or F, and the other is H. In some embodiments R1is H and R2is halo. In some embodiments R1is H and R2is F. In some embodiments R1is H and R2is Cl. In some embodiments R1is halo and R2is H. In some embodiments R1is F and R2is H. In some embodiments R1is Cl and R2is H. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Q1is C-L-R. In some embodiments Q2is C-L-R. In some embodiments Q3is C-L-R. In some embodiments Q1and Q3are each, independently, CH, and Q2is C-L-R. In some embodiments L is -O-, -(CH2)qO- or -O(CH2)q-.In some embodiments Q1is C-L-R and L is -O-, -(CH2)qO- or -O(CH2)q-.In some embodiments Q2is C-L-R and L is -O-, -(CH2)qO- or -O(CH2)q-. In some embodiments Q1and Q3are each, independently, CH; Q2is C-L-R; and L is -O-, -(CH2)qO- or -O(CH2)q-. In some embodiments Q3is C-L-R and L is -O-, -(CH2)qO- or -O(CH2)q-.In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein L is -O-. In some embodiments Q1is C-L-R and L is -O-.In some embodiments Q2is C-L-R and L is -O-.In some embodiments Q1and Q3are each, independently, CH; Q2is C-L-R; and L is -O-. In some embodiments Q3is C-L-R and L is -O-. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein L is -(CH2)qO. In some embodiments Q1is C-L-R and L is -(CH2)qO. In some embodiments Q2is C-L-R and L is -(CH2)qO. In some embodiments Q3is C-L-R and L is -(CH2)qO. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein L is -O(CH2)q-. In some embodiments Q1is C-L-R and L is -O(CH2)q-. In some embodiments Q2is C-L-R and L is - O(CH2)q-. In some embodiments Q3is C-L-R and L is -O(CH2)q-. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein L is -O(CH2)2-. In some embodiments Q1is C-L-R and L is -O(CH2)2-. In some embodiments Q2is C-L-R and L is - O(CH2)2-. In some embodiments Q3is C-L-R and L is -O(CH2)2-. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein L is -C(O)-; - O(CH2)qC(O)-; -C(O)NRy-; -O(CH2)qC(O)NRy-; -(CH2)qC(O)-; or -(CH2)qC(O)O-. In some embodiments Q1is C-L-R and L is -C(O)-; -O(CH2)qC(O)-; -C(O)NRy-; -O(CH2)qC(O)NRy-; - (CH2)qC(O)-; or -(CH2)qC(O)O-. In some embodiments Q2is C-L-R and L is -C(O)-; - O(CH2)qC(O)-; -C(O)NRy-; -O(CH2)qC(O)NRy-; -(CH2)qC(O)-; or -(CH2)qC(O)O-. In some embodiments Q3is C-L-R and L is -C(O)-; -O(CH2)qC(O)-; -C(O)NRy-; -O(CH2)qC(O)NRy-; - (CH2)qC(O)-; or -(CH2)qC(O)O-. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein R is H, Raor Rb. In some embodiments Q1is C-L-R and R is H, Raor Rb. In some embodiments Q2is C-L-R and R is H, Raor Rb. In some embodiments Q3is C-L-R and R is H, Raor Rb. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein R is Ra. In some embodiments Q1, Q2, or Q3is C-L-Raand Rais a 3-10 membered N-heterocycle. In some embodiments Q1, Q2, or Q3is C-L-Raand Rais a 4-7 membered N-heterocycle. In some embodiments Q1, Q2, or Q3is C-L-Raand Rais a 6 membered N-heterocycle. In some embodiments Q1, Q2, or Q3is C-L-Raand Rais piperidine, 1,2-diazinane, 1,3-diazinane, 1,4-diazinane, 1,2- oxazinane, 1,3-oxazinane, or 1,4-oxazinane. In some embodiments Q1, Q2, or Q3is C-L-Raand Rais substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, -CN, -S(O)2OH, C1-C4alkylamino, C1-C5 alkoxy, C2-C5 alkoxyalkyl, 4-6 membered heterocycle, C1-C7 alkyl, -S(O)2C1- C3 alkyl and -C(O)-C3-C6 carbocycle, wherein the C1-C7 alkyl is optionally substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, -CN, C2-C8ester, and C1-C5alkoxy. In some embodiments Q1, Q2, or Q3is C-L-Raand Rais substituted with C1-C7 alkyl, wherein the C1-C7 alkyl is optionally substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, -CN, C2-C8ester, and C1-C5alkoxy. In some embodiments Q1, Q2, or Q3is C-L-Raand Rais substituted with C1-C7 alkyl substituted with oxo. In some embodiments Q1, Q2, or Q3is C-L-Raand Rais substituted with C1- C7alkyl substituted with a C1-C5alkoxy. In some embodiments Q1, Q2, or Q3is C-L-Raand Rais substituted with methyl. In some embodiments Q1, Q2, or Q3is C-L-Raand L is -O(CH2)q- and Rais an optionally substituted 3-10 membered N-heterocycle. In some embodiments Q1, Q2, or Q3is C-L-Raand L is -O(CH2)q- and Rais an unsubstituted 3-10 membered N-heterocycle. In some embodiments Q1, Q2, or Q3is C-L-Raand L is -O(CH2)2- and Rais an optionally substituted 3-10 membered N-heterocycle. In some embodiments Q1, Q2, or Q3is C-L-Raand L is -O(CH2)2- and Rais an optionally substituted 4-7 membered N-heterocycle. In some embodiments Q1, Q2, or Q3is C-L-Raand L is -O(CH2)2- and Rais a 4-7 membered N-heterocycle substituted with hydroxy, methyl, or amino. In some embodiments Q1, Q2, or Q3is C-L-Raand L is -O(CH2)2- and Rais an unsubstituted 4-7 membered N-heterocycle. In some embodiments, Q1, Q2, or Q3is C-L-Raand L is -O(CH2)2- and Rais piperazinyl. In some embodiments Q1and Q3are each, independently, CH, Q2is C-L-Rawherein L is -O(CH2)2- and Rais piperazinyl. In some embodiments Q1, Q2, or Q3is C-L-Raand L is -O(CH2)3- and Rais an optionally substituted 3-10 membered N-heterocycle. In some embodiments Q1, Q2, or Q3is C-L-Raand L is -O(CH2)3- and Rais a 4-7 membered N-heterocycle. In some embodiments Q1, Q2, or Q3is C-L- Raand L is -O(CH2)3- and Rais an unsubstituted 4-7 membered N-heterocycle. In some embodiments Q1, Q2, or Q3is C-L-Raand L is -O(CH2)3- and Rais a 4-7 membered N-heterocycle substituted with hydroxy, methyl, or amino. In some embodiments Q1, Q2, or Q3is C-L-Raand L is -O- and Rais an optionally substituted 3-10 membered N-heterocycle. In some embodiments Q1, Q2, or Q3is C-L-Raand L is -O- and Rais a 4-7 membered N-heterocycle. In some embodiments Q1, Q2, or Q3is C-L-Raand L is -O- and Rais an unsubstituted 4-7 membered N-heterocycle. In some embodiments Q1, Q2, or Q3is C-L-Raand L is -O- and Rais a 4-7 membered N-heterocycle substituted with hydroxy, methyl, or amino. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein R is Rb. In some embodiments Q1, Q2, or Q3is C-L-Rband Rbis substituted with 1 to 4 substituents independently selected from: halo, oxo, hydroxy, carboxy, amino, -CN, C2-C4 alkynyl, C2-C6 carbamate, C1-C8amide, C1-C4sulfonyl, C1-C4sulfonamide, C1-C4alkylamino, C1-C5alkoxy, C3- C6carbocycle, and 3-10 membered heterocycle, wherein the C3-C6carbocycle is optionally substituted with 1 to 4 substituents independently selected from hydroxy, halo, and carboxy, and wherein the 3-10 membered heterocycle is optionally substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, -CN, -S(O)2OH, C1-C4alkylamino, C1-C5 alkoxy, C2-C5 alkoxyalkyl, 4-6 membered heterocycle, and C1-C7 alkyl, wherein the C1-C7 alkyl is optionally substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, -CN, C2-C8ester, and C1-C5alkoxy. In some embodiments Q1and Q3are each CH, Q2is C-L-Rbwherein Rbis a C1-C7 alkyl substituted with 1 to 4 substituents independently selected from: halo, oxo, hydroxy, carboxy, amino, -CN, C2-C4alkynyl, C2-C6carbamate, C1-C8amide, C1-C4sulfonyl, C1-C4sulfonamide, C1-C4alkylamino, C1-C5alkoxy, C3-C6carbocycle, and 3-10 membered heterocycle, wherein the C3-C6 carbocycle is optionally substituted with 1 to 4 substituents independently selected from hydroxy, halo, and carboxy, and wherein the 3-10 membered heterocycle is optionally substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, -CN, - S(O)2OH, C1-C4 alkylamino, C1-C5 alkoxy, C2-C5 alkoxyalkyl, 4-6 membered heterocycle, and C1-C7 alkyl, wherein the C1-C7 alkyl is optionally substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, -CN, C2-C8ester, and C1-C5alkoxy. In some embodiments Q1, Q2, or Q3is C-L-Rband Rbis a C1-C7 alkyl, wherein one or two methylene groups from the C1-C7 alkyl are optionally independently replaced with NRe, O, S, S(O) or CW1W2wherein W1and W2together form a C3-C6carbocycle, and one or two single bonds in a C2-C7alkyl chain are optionally independently replaced with a double or triple bond(s). In some embodiments Q1and Q3are each, independently, CH, Q2is C-L-Rbwherein Rbis a C1-C7 alkyl, wherein one or two methylene groups from the C1-C7 alkyl are optionally independently replaced with NReor O and one or two single bonds in a C2-C7alkyl chain are optionally independently replaced with a double or triple bond(s). In some embodiments Q1, Q2, or Q3is C-L-Rband Rbis substituted with 1 to 4 substituents independently selected from C3-C6carbocycle, wherein the C3-C6carbocycle is substituted with 1 to 4 substituents independently selected from hydroxy, halo, and carboxy. In some embodiments Q1, Q2, or Q3is C-L-Rband Rbis substituted with 1 to 4 substituents independently selected from C3-C6carbocycle, wherein the C3-C6carbocycle is substituted with 1 to 4 substituents independently selected from hydroxy and halo. In some embodiments Q1, Q2, or Q3is C-L-Rband Rbis substituted with hydroxy. In some embodiments Q1, Q2, or Q3is C-L-Rband Rbis substituted with a 3-10 membered heterocycle. In some embodiments, the 3-10 membered heterocycle is unsubstituted. In some embodiments Q1, Q2, or Q3is C-L-Rband Rbis substituted with a 3-10 membered N-heterocycle. In some embodiments Q1, Q2, or Q3is C-L-Rband Rbis substituted with a 4-7 membered N-heterocycle. In some embodiments Q1, Q2, or Q3is C-L-Rband Rbis substituted with a 6 membered N-heterocycle. In some embodiments, the N-heterocycle is unsubstituted. In some embodiments Q1, Q2, or Q3is C-L-Rband Rbis substituted with piperazinyl. In some embodiments Q1and Q3are each, independently, CH, Q2is C-L-Rbwherein Rbis substituted with a 3-10 membered N-heterocycle. In some embodiments Q1and Q3are each, independently, CH, Q2is C-L-Rbwherein Rbis substituted with a 4-7 membered N-heterocycle. In some embodiments Q1and Q3are each, independently, CH, Q2is C-L-Rbwherein Rbis substituted with a 6 membered N-heterocycle. In some embodiments, the N-heterocycle is unsubstituted. In some embodiments Q1and Q3are each, independently, CH, Q2is C-L-Rbwherein Rbis substituted with piperazinyl. In some embodiments Q1, Q2, or Q3is C-L-Rband Rbis substituted with a 3-10 membered heterocycle, such as, but not limited to a N-heterocycle, such as, but not limited to a 4-7 membered N-heterocycle, wherein the heterocycle is substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, -CN, -S(O)2OH, C1-C4alkylamino, C1-C5alkoxy, C2-C5 alkoxyalkyl, 4-6 membered heterocycle, and C1-C7 alkyl, wherein the C1-C7 alkyl is optionally substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, -CN, C2-C8ester, and C1-C5alkoxy. In some embodiments Q1, Q2, or Q3is C-L-Rband Rbis substituted with a 3-10 membered heterocycle, such as, but not limited to a N-heterocycle, such as, but not limited to a 4-7 membered N-heterocycle, wherein the heterocycle is substituted with C1-C7alkyl, oxo, and / or halo. In some embodiments Q1, Q2, or Q3is C-L-Rband Rbis substituted with amino, C1-C8 amide, and / or C1-C4 alkylamino. In some embodiments Q1, Q2, or Q3is C-L-Rband Rbis substituted with oxo, hydroxy, and / or carboxy. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Q1, Q2, or Q3is C- L-Rband Rbis substituted with carboxy. In some embodiments Q1and Q3are each, independently, CH, Q2is C-L-Rbwherein Rbis substituted with oxo, hydroxy, and / or carboxy. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Q1and Q3are each, independently, CH, Q2is C-L-Rbwherein Rbis substituted with carboxy. In some embodiments Q1, Q2, or Q3is C-L-Rband Rbis a C1-C7 alkyl, wherein one or two methylene groups from the C1-C7alkyl are independently replaced with NRe. In some embodiments Q1, Q2, or Q3is C-L-Rband Rbis a C1-C7alkyl, wherein one methylene group from the C1-C7 alkyl is independently replaced with NRe. In some embodiments, Reis a C1-C8 alkyl. In some embodiments Q1, Q2, or Q3is C-L-Rband Rbis a C1-C7alkyl, wherein one methylene group from the C1-C7 alkyl is independently replaced with -N(CH3)-. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Q1, Q2, or Q3is C-L-Rband Rbis a C1-C7 alkyl, wherein one or two methylene groups from the C1-C7 alkyl are independently replaced with NRe. In some embodiments Q1, Q2, or Q3is C-L-Rband Rbis a C1-C7 alkyl, wherein one methylene group from the C1-C7alkyl is independently replaced with NRe. In some embodiments, Reis a C1-C8alkyl. In some embodiments Q1, Q2, or Q3is C-L-Rband Rbis a C1-C7 alkyl, wherein one methylene group from the C1-C7 alkyl is independently replaced with - N(CH3)-. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Q1and Q3are each, independently, CH, Q2is C-L-Rbwherein Rbis a C1-C7 alkyl, wherein one methylene group from the C1-C7alkyl is independently replaced with NRe. In some embodiments, Reis a C1-C8alkyl. In some Q1and Q3are each, independently, CH, Q2is C-L-Rbwherein Rbis a C1-C7 alkyl, wherein one methylene group from the C1-C7 alkyl is independently replaced with -N(CH3)-. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis an optionally substituted C1-C7alkyl. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis an optionally substituted C1-C5 alkyl. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis an optionally substituted C1-C3 alkyl. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis a C1-C7alkyl substituted with a 3-10 membered heterocycle. In some embodiments, the 3-10 membered heterocycle is unsubstituted. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis a C1-C7alkyl substituted with a 3-10 membered N-heterocycle. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis a C1-C7 alkyl substituted with a 4-7 membered N-heterocycle. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis a C1-C7alkyl substituted with a 6 membered N-heterocycle. In some embodiments, the N-heterocycle is unsubstituted. In some embodiments Q1, Q2, or Q3is C- L-Rb, L is -O-, and Rbis a C1-C7 alkyl substituted with piperazinyl. In some embodiments Q1and Q3are each, independently, CH, Q2is C-L-Rbwherein L is -O-, and Rbis a C1-C7alkyl substituted with a 3-10 membered N-heterocycle. In some embodiments Q1and Q3are each, independently, CH, Q2is C-L-Rbwherein L is -O-, and Rbis a C1-C7 alkyl substituted with a 4-7 membered N-heterocycle. In some embodiments Q1and Q3are each, independently, CH, Q2is C-L-Rbwherein L is -O-, and Rbis a C1-C7alkyl substituted with a 6 membered N-heterocycle. In some embodiments, the N-heterocycle is unsubstituted. In some embodiments Q1and Q3are each, independently, CH, Q2is C-L-Rbwherein L is -O-, and Rbis a C1-C7alkyl substituted with piperazinyl. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis an C1-C5alkyl substituted with 1 to 4 substituents independently selected from amino, carboxy, oxy, and hydroxy. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis an C1-C3 alkyl substituted with 1 to 4 substituents independently selected from amino, carboxy, oxy, and hydroxy. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis an C1-C7 alkyl substituted with carboxy. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis an C1-C5 alkyl substituted with carboxy. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis an C4alkyl substituted with carboxy. In some embodiments Q1and Q3are each, independently, CH, Q2is C-L-Rbwherein L is O, and Rbis a C1-C7alkyl, wherein the C1-C7alkyl is substituted with carboxy. In some embodiments Q1and Q3are each, independently, CH, Q2is C-L-Rbwherein L is -O-, and Rbis an C1-C5 alkyl substituted with carboxy. In some embodiments Q1and Q3are each, independently, CH, Q2is C-L-Rbwherein L is -O-, and Rbis an C4 alkyl substituted with carboxy. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis an C1-C5alkyl substituted with 1 to 4 substituents independently selected from -CN, C2-C4 alkynyl, C2-C6 carbamate, and C1-C8 amide. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis an C1-C3 alkyl substituted with 1 to 4 substituents independently selected from -CN, C2-C4alkynyl, C2-C6carbamate, and C1-C8 amide. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis an unsubstituted C1-C5 alkyl. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis an unsubstituted C1-C3alkyl. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis an optionally substituted C1-C7alkyl, wherein one or two methylene groups from the C1-C7alkyl is independently replaced with NReor O. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is O, and Rbis a C1-C7 alkyl, wherein one methylene group from the C1-C7alkyl is independently replaced with NRe. In some embodiments Q1and Q3are each, independently, CH, Q2is C-L-Rbwherein L is O and Rbis a C1-C7 alkyl, wherein one methylene group from the C1-C7 alkyl is independently replaced with NRe. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis an optionally substituted C1-C7 alkyl, wherein one methylene group from the C1-C7 alkyl is replaced with NH. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis an optionally substituted C1-C7alkyl, wherein one methylene group from the C1-C7alkyl is replaced with -N(CH3)-. In some embodiments Q1, Q2, or Q3is C-L-Rb, L is -O-, and Rbis an optionally substituted C4 alkyl, wherein one methylene group from the C4 alkyl is replaced with -N(CH3)-. In some embodiments, Reis a C1-C8alkyl. In some embodiments Q1and Q3are each, independently, CH, Q2is C-L-Rbwherein L is -O- and Rbis a C1-C7 alkyl, wherein one methylene group from the C1-C7 alkyl is independently replaced with -NCH3-. In some embodiments Q1and Q3are each, independently, CH, Q2is C-L-Rbwherein L is -O-, and Rbis an optionally substituted C4alkyl, wherein one methylene group from the C4alkyl is replaced with -N(CH3)-. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Q1, Q2, or Q3is C-L-Rc.In some embodiments Q1, Q2, or Q3is C-L-Rcand Rcis substituted with 1 to 4 substituents independently selected from hydroxy, halo, carboxy, C1-C3 alkyl, and CN. In some embodiments Q1, Q2, or Q3is C-L-Rcand Rcis substituted with 1 to 4 substituents independently selected from hydroxy, halo, and carboxy. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein X is CH2. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Y is a phenyl or a 5-6 membered heteroaryl, wherein the phenyl or 5-6 membered heteroaryl is optionally substituted with 1 to 3 substituents independently selected from halo, C1-C3 alkyl, C1-C3 alkoxy, -CN, C1-C3 and haloalkyl. In some embodiments Y is a phenyl or a 5-6 membered heteroaryl, wherein the phenyl or 5-6 membered heteroaryl is optionally substituted with 1 to 3 substituents independently selected from halo and C1-C3 alkyl. In some embodiments Y is phenyl. In some embodiments Y is a 5-6 membered N- heteroaryl. In some embodiments Y is a pyridinyl. In some embodiments Y is substituted. In some embodiments Y is substituted with 1-3 substituents independently selected from halo, C1-C3 alkyl, C1-C3 alkoxy, -CN, C1-C3 and haloalkyl. In some embodiments Y is substituted with halo. In some embodiments Y is substituted with -Cl. In some embodiments Y is substituted with C1-C3 alkyl. In some embodiments Y is substituted with -CH3. In some embodiments Y is substituted with cyclopropyl. In some embodiments Y is not substituted. In some embodiments Y is phenyl, substituted with 1 substituent selected from halo, C1- C3 alkyl, C1-C3 alkoxy, -CN, C1-C3 haloalkyl, and cyclopropyl. In some embodiments Y is phenyl, substituted with 1 substituent selected from halo and C1-C3 alkyl. In some embodiments Y is phenyl, substituted with 1 substituent selected from -Cl and -CH3. In some embodiments Y is phenyl, substituted with -Cl. In some embodiments Y is pyridinyl, substituted with 1 substituent selected from halo, C1- C3alkyl, C1-C3alkoxy, -CN, C1-C3haloalkyl, and cyclopropyl. In some embodiments Y is pyridinyl, substituted with 1 substituent selected from halo and C1-C3 alkyl. In some embodiments Y is pyridinyl, substituted with 1 substituent selected from -Cl and -CH3. In some embodiments Y is pyridinyl, substituted with -CH3. In some embodiments Y is 4-methylpyridinyl. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein G is N. In some embodiments G is CH. In some embodiments Gb is CR5. In some embodiments Gb is N. In some embodiments Gb is CH. In some embodiments Ga is CR5. In some embodiments G is N, Ga is CR5and Gb is N. In some embodiments G is CH, Ga is CR5and Gbis N. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein R5is ; Rzis H, C1-C3 alkyl, or Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4- 6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3alkyl, and: when Rzis H or C1-C3 alkyl: (i) Zaand Zbare, independently, H, C1-C5 alkyl, or halo, wherein the C1-C5 alkyl is optionally substituted with hydroxy, or Zaand Zbtogether form a saturated C3- C6 carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3 alkoxy, and C1-C3 alkyl optionally substituted with hydroxy, or Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, C1-C3 alkyl, halo, hydroxy, C1-C3 alkoxy, C2-C5 alkoxyalkyl, C3-C6 carbocycle, 5-6 membered heteroaryl, or phenyl, wherein the C1-C3alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide, or (ii) Za, Zband Zctogether form a 5-membered bicyclic ring system containing a bridge of 1 carbon atom; when Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3alkyl: Zband Zcare, independently, H, C1-C3 alkyl, or C3-C6 carbocycle, or Zband Zctogether form a C3-C6 carbocycle or a 4-6 membered heterocycle, or Zbtogether with Rzand Zaform a 7-membered heterobicyclic ring system containing a bridge of 2 carbon atoms, and Zcis H. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein p is 0. In some embodiments p is 1. In some embodiments p is 2. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H or C1-C3 alkyl. In some embodiments, Rzis H. In other embodiments, Rzis C1-C3 alkyl. In some embodiments, Rzis selected from CH3and C2H5. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H or C1-C3 alkyl, and wherein: Zaand Zbare, independently, H, C1-C5 alkyl, or halo, wherein the C1-C5 alkyl is optionally substituted with hydroxy, or Zaand Zbtogether form a saturated C3-C6 carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3alkoxy, and C1-C3alkyl optionally substituted with hydroxy, or Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, C1-C3alkyl, halo, hydroxy, C1-C3alkoxy, C2-C5alkoxyalkyl, C3-C6carbocycle, 5-6 membered heteroaryl, or phenyl, wherein the C1-C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3amide. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein p is 0, wherein Rzis H or C1-C3 alkyl, and wherein: Zaand Zbare, independently, H, C1-C5alkyl, or halo, wherein the C1-C5alkyl is optionally substituted with hydroxy, or Zaand Zbtogether form a saturated C3-C6 carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3alkoxy, and C1-C3alkyl optionally substituted with hydroxy, or Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, C1-C3 alkyl, halo, hydroxy, C1-C3 alkoxy, C2-C5 alkoxyalkyl, C3-C6 carbocycle, 5-6 membered heteroaryl, or phenyl, wherein the C1-C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein p is 1, wherein Rzis H or C1-C3 alkyl, and wherein: Zaand Zbare, independently, H, C1-C5alkyl, or halo, wherein the C1-C5alkyl is optionally substituted with hydroxy, or Zaand Zbtogether form a saturated C3-C6 carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3alkoxy, and C1-C3alkyl optionally substituted with hydroxy, or Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, C1-C3 alkyl, halo, hydroxy, C1-C3 alkoxy, C2-C5 alkoxyalkyl, C3-C6 carbocycle, 5-6 membered heteroaryl, or phenyl, wherein the C1-C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4alkylamino, and C1-C3 amide. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein p is 2, wherein Rzis H or C1-C3alkyl, and wherein: Zaand Zbare, independently, H, C1-C5 alkyl, or halo, wherein the C1-C5 alkyl is optionally substituted with hydroxy, or Zaand Zbtogether form a saturated C3-C6 carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3 alkoxy, and C1-C3 alkyl optionally substituted with hydroxy, or Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, C1-C3 alkyl, halo, hydroxy, C1-C3 alkoxy, C2-C5 alkoxyalkyl, C3-C6 carbocycle, 5-6 membered heteroaryl, or phenyl, wherein the C1-C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H or C1-C3 alkyl, and wherein Zaand Zbare, independently, H, C1-C5alkyl, or halo, and wherein Zcis hydroxy, C2- C5 alkoxyalkyl, or C1-C3 alkyl, wherein the C1-C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H or C1-C3 alkyl, and wherein Zaand Zbare, independently, H, C1-C5 alkyl, or halo, and wherein Zcis C1-C3 alkyl, wherein the C1-C3alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4alkylamino, and C1-C3amide. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H, and wherein Zaand Zbare, independently, H, C1-C5 alkyl, or halo, and wherein Zcis CH3. In some embodiments Rzis H, and Zaand Zbare, independently, CH3 or halo, and Zcis CH3. In some embodiments Rzis H, and Zaand Zbare, independently, CH3or F, and Zcis CH3. In some embodiments Rzis H, and Za, Zband Zcare, independently, CH3. In some embodiments Rzis H, and Zaand Zbare, independently, H or C4 alkyl, and Zcis CH3. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H, and wherein Zaand Zbare, independently, H, C1-C5 alkyl, or halo, and wherein Zcis C1-C3 alkyl, wherein the C1- C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4alkylamino, and C1-C3amide. In some embodiments Rzis H, and Zaand Zbare, independently, H, C1-C5 alkyl, or halo, and Zcis unsubstituted C1-C3 alkyl. In some embodiments Rzis H, and Zaand Zbare, independently, H or C1-C3 alkyl, and Zcis unsubstituted C1-C3 alkyl. In some embodiments Rzis H, and Zaand Zbare, independently, H or C1-C3alkyl, and Zcis C1-C3alkyl, wherein the C1-C3 alkyl is substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide. In some embodiments, the C1-C3 alkyl is substituted with hydroxy. In some embodiments, the C1-C3alkyl is substituted with oxo and C1- C4alkylamino. In some embodiments, the C1-C3alkyl is substituted with C1-C3amide. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H, and wherein Zaand Zbare, independently, H, C1-C5alkyl, or halo, and wherein Zcis hydroxy. In some embodiments Rzis H, and Zaand Zbare, independently, CH3, and Zcis hydroxy. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H, and wherein Zaand Zbare, independently, C1-C5 alkyl, and wherein Zcis C2-C5 alkoxyalkyl. In some embodiments Rzis H, and Zaand Zbare, independently, CH3, and Zcis C2 alkoxyalkyl. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis C1-C3alkyl, and wherein Zaand Zbare, independently, H, C1-C5 alkyl, or halo, and wherein Zcis CH3. In some embodiments Rzis C1-C3 alkyl, and Za, Zband Zcare, independently, CH3. In some embodiments Rzis CH3, and Za, Zband Zcare, independently, CH3. In some embodiments Rzis C2H5, and Zaand Zbare, independently, H, and Zcis CH3. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H or C1-C3alkyl, and wherein Zaand Zbare, independently, H, C1-C5 alkyl, or halo, and wherein Zcis hydroxy, C2- C5 alkoxyalkyl, or C1-C3 alkyl, wherein the C1-C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4alkylamino, and C1-C3amide, and wherein p is 0. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H or C1-C3 alkyl, and wherein Zaand Zbare, independently, H, C1-C5alkyl, or halo, and wherein Zcis hydroxy, C2- C5 alkoxyalkyl, or C1-C3 alkyl, wherein the C1-C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide, and wherein p is 1. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H or C1-C3 alkyl, and wherein Zaand Zbare, independently, H, C1-C5alkyl, or halo, and wherein Zcis hydroxy, C2- C5alkoxyalkyl, or C1-C3alkyl, wherein the C1-C3alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide, and wherein p is 2. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H, wherein Za, Zband Zcare, independently, CH3, and wherein p is 0. In some embodiments Rzis H, Za, Zband Zcare, independently, CH3, and p is 1. In some embodiments Rzis H, Za, Zband Zcare, independently, CH3, and p is 2. In some embodiments Rzis H, and Zaand Zbare, independently, CH3 or F, Zcis CH3, and p is 1. In some embodiments Rzis H, and Zaand Zbare, independently, H or C4 alkyl, and Zcis CH3, and wherein p is 0. In some embodiments Rzis H, and Zaand Zbare, independently, H or C1-C3 alkyl, and Zcis unsubstituted C1-C3 alkyl, and p is 1. In some embodiments Rzis H, and Zaand Zbare, independently, H or C1-C3alkyl, and Zcis C1-C3 alkyl, wherein the C1-C3 alkyl is substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide, and wherein p is 0. In some embodiments Rzis H, and Zaand Zbare, independently, CH3, Zcis hydroxy, and p is 1. In some embodiments Rzis H, and wherein Zaand Zbare, independently, CH3, wherein Zcis C2 alkoxyalkyl, and wherein p is 0. In some embodiments Rzis CH3, Za, Zband Zcare, independently, CH3, and p is 0. In some embodiments Rzis C2H5, Zaand Zbare, independently, H, and Zcis CH3, and p is 0. In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbare, independently, H or C1-C5alkyl, wherein the C1-C5 alkyl is optionally substituted with hydroxy, and Zcis C3-C6 carbocycle. In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbare, independently, H or C1-C3 alkyl, wherein the C1-C3alkyl is optionally substituted with hydroxy, and wherein Zcis C3carbocycle. In some embodiments Rzis H, and Zaand Zbare, independently, H or C1-C3alkyl substituted with hydroxy, and Zcis C3 carbocycle. In some embodiments Rzis H, and Zaand Zbare, independently, H or CH3, and Zcis C3 carbocycle. In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbare, independently, H or C1-C5alkyl, wherein the C1-C5 alkyl is optionally substituted with hydroxy, and Zcis C3-C6 carbocycle, and p is 0. In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbare, independently, H or C1-C5alkyl, wherein the C1-C5 alkyl is optionally substituted with hydroxy, and Zcis C3-C6 carbocycle, and p is 1. In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbare, independently, H or C1-C5 alkyl, wherein the C1-C5alkyl is optionally substituted with hydroxy, and Zcis C3-C6carbocycle, and p is 2. In some embodiments Rzis H, and Zaand Zbare, independently, H or C1-C3 alkyl substituted with hydroxy, Zcis C3carbocycle, and p is 0. In some embodiments Rzis H, and Zaand Zbare, independently, H or CH3, Zcis C3 carbocycle, and p is 0. In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbare, independently, H or C1-C5alkyl, and Zcis a 5-6 membered heteroaryl, or phenyl. In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbare, independently, H or CH3, and Zcis thiazolyl or phenyl. In some embodiments Rzis H, and Zaand Zbare, independently, H or CH3, and Zcis thiazolyl. In some embodiments Rzis H, and Zaand Zbare, independently, H or CH3, and Zcis phenyl. In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbare, independently, H or C1-C5 alkyl, and Zcis 5-6 membered heteroaryl, or phenyl, and p is 0. In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbare, independently, H or C1-C5alkyl, and Zcis 5-6 membered heteroaryl, or phenyl, and p is 1. In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbare, independently, H or C1-C5 alkyl, and Zcis 5-6 membered heteroaryl, or phenyl, and p is 2. In some embodiments Rzis H, and Zaand Zbare, independently, H or CH3, Zcis thiazolyl, and p is 0. In some embodiments Rzis H, and Zaand Zbare, independently, H or CH3, Zcis phenyl, and p is 0. In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbtogether form a saturated C3- C6 carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3alkoxy, and C1-C3alkyl optionally substituted with hydroxy, and wherein Zcis H, halo, C1-C3 alkoxy, or C1-C3 alkyl optionally substituted with hydroxy or halo. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6 carbocycle, and wherein Zcis H, halo, C1-C3alkoxy, or C1-C3alkyl optionally substituted with hydroxy or halo. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6 carbocycle, and Zcis H. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6carbocycle, and Zcis F. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6 carbocycle, and Zcis C1-C3 alkoxy. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6carbocycle, and Zcis C1-C3alkyl. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6 carbocycle, and Zcis CH3. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6 carbocycle, and Zcis C1-C3 alkyl substituted with hydroxy. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6carbocycle, and Zcis C1-C3alkyl substituted with halo, optionally wherein halo is F. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6 carbocycle substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3 alkoxy, and C1-C3alkyl optionally substituted with hydroxy, and wherein Zcis H, halo, C1-C3alkoxy, or C1- C3 alkyl optionally substituted with hydroxy or halo. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6 carbocycle substituted with 1 or 2 substituents independently selected from halo, and wherein Zcis H, optionally wherein halo is F. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6 carbocycle substituted with hydroxy, and wherein Zcis H. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6 carbocycle substituted with C1-C3alkoxy, and Zcis H. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6carbocycle substituted with C1-C3alkyl, wherein the C1-C3alkyl is substituted with hydroxy, and wherein Zcis H. In some embodiments Rzis C1-C3 alkyl, and Zaand Zbtogether form a saturated C3-C6 carbocycle, and Zcis H, halo, C1-C3alkoxy, or C1-C3alkyl optionally substituted with hydroxy or halo. In some embodiments Rzis C1-C3 alkyl, and Zaand Zbtogether form a saturated C3-C6 carbocycle, and Zcis H. In some embodiments Rzis C1-C3alkyl, and Zaand Zbtogether form a saturated C3-C6carbocycle substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3 alkoxy, and C1-C3 alkyl optionally substituted with hydroxy, and Zcis H, halo, C1-C3 alkoxy, or C1-C3alkyl optionally substituted with hydroxy or halo. In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbtogether form a saturated C3- C6 carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3 alkoxy, and C1-C3 alkyl optionally substituted with hydroxy, and Zcis H, halo, C1- C3alkoxy, or C1-C3alkyl optionally substituted with hydroxy or halo, and p is 0. In some embodiments Rzis H or C1-C3 alkyl, and wherein Zaand Zbtogether form a saturated C3-C6 carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3alkoxy, and C1-C3alkyl optionally substituted with hydroxy, and Zcis H, halo, C1-C3 alkoxy, or C1-C3 alkyl optionally substituted with hydroxy or halo, and p is 1. In some embodiments Rzis H or C1-C3 alkyl, and wherein Zaand Zbtogether form a saturated C3-C6carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3alkoxy, and C1-C3alkyl optionally substituted with hydroxy, and wherein Zcis H, halo, C1-C3 alkoxy, or C1-C3 alkyl optionally substituted with hydroxy or halo, and p is 2. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6carbocycle, Zcis H, and p is 0. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6 carbocycle, Zcis H, and p is 1. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6carbocycle, Zcis H, and p is 2. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6 carbocycle, and Zcis F, and p is 1. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6carbocycle, and Zcis C1-C3alkoxy, and p is 1. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6 carbocycle, Zcis CH3, and p is 0. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6 carbocycle, Zcis CH3, and p is 1. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6carbocycle, and Zcis C1-C3 alkyl substituted with hydroxy, and p is 0. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6 carbocycle, and Zcis C1-C3alkyl substituted with halo, and p is 1. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6 carbocycle substituted with 1 or 2 substituents independently selected from halo, Zcis H, and p is 0. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6carbocycle substituted with hydroxy, Zcis H, and p is 0. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6 carbocycle substituted with C1-C3alkoxy, Zcis H, and p is 0. In some embodiments Rzis H, and Zaand Zbtogether form a saturated C3-C6 carbocycle substituted with C1-C3 alkyl, the C1-C3 alkyl is substituted with hydroxy, Zcis H, and p is 0. In some embodiments Rzis C1-C3alkyl, and Zaand Zbtogether form a saturated C3-C6carbocycle, Zcis H, and p is 0. In some embodiments Rzis C1-C3 alkyl, and Zaand Zbtogether form a saturated C3-C6 carbocycle, and Zcis H, and p is 1. In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H. In some embodiments, the saturated 4-6 membered heterocycle contains O or S. In some embodiments Rzis H, and Zaand Zbtogether form a saturated 4-6 membered heterocycle, and Zcis H. In some embodiments, the saturated 4-6 membered heterocycle contains O or S. In some embodiments, the saturated 4-6 membered heterocycle is tetrahydrofuran. In some embodiments, the saturated 4-6 membered heterocycle is tetrahydropyran. In some embodiments Rzis H, and Zaand Zbtogether form a saturated 4-6 membered heterocycle substituted with 1 or 2 substituents independently selected from oxo, and Zcis H. In some embodiments, the saturated 4-6 membered heterocycle is thietane 1,1-dioxide. In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, and p is 0. In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, and p is 1. In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, and p is 2. In some embodiments Rzis H, and Zaand Zbtogether form a saturated 4-6 membered heterocycle, Zcis H, and p is 0. In some embodiments Rzis H, and Zaand Zbtogether form a saturated 4-6 membered heterocycle, Zcis H, and p is 1. In some embodiments Rzis H, and Zaand Zbtogether form a saturated 4-6 membered heterocycle substituted with 1 or 2 substituents independently selected from oxo, Zcis H, and p is 0. In some embodiments Rzis H or C1-C3 alkyl, and Za, Zband Zctogether form a 5-membered bicyclic ring system containing a bridge of 1 carbon atom. In some embodiments Rzis H, and Za, Zband Zctogether form a 5-membered bicyclic ring system containing a bridge of 1 carbon atom. In some embodiments, the bicyclic ring . In some embodiments Rzis H, and Za, form a 5-membered bicyclic ring system containing a bridge of 1 carbon atom, and p is 0. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, and wherein Zband Zcare, independently, H, C1-C3 alkyl, or C3-C6 carbocycle. In some embodiments Rztogether with Zaforms a 4-5 membered N-heterocycle optionally substituted with 1 or 2 CH3, and Zband Zcare, independently, H, CH3, or C3carbocycle. In some embodiments disclosed Rztogether with Zaforms a 4-5 membered N-heterocycle, and Zband Zcare, independently, H or CH3. In some embodiments Rztogether with Zaforms a 4-5 membered N-heterocycle substituted with 2 CH3, and Zband Zcare, independently, H. In some embodiments Rztogether with Zaforms a 4-5 membered N-heterocycle, and Zband Zcare, independently, H or C3-C6 carbocycle. In some embodiments, the 4-5 membered N-heterocycle is selected from piperidinyl, pyrrolidinyl, and azetidinyl. In some embodiments, the 4-5 membered N-heterocycle is pyrrolidinyl. In some embodiments, the 4-5 membered N-heterocycle is azetidinyl. In some embodiments Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3alkyl, and Zband Zcare, independently, H, C1-C3alkyl, or C3-C6carbocycle, and p is 0. In some embodiments Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, and Zband Zcare, independently, H, C1-C3 alkyl, or C3-C6 carbocycle, and p is 1. In some embodiments Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, and Zband Zcare, independently, H, C1-C3 alkyl, or C3-C6 carbocycle, and p is 2. In some embodiments Rztogether with Zaforms a 4-5 membered N-heterocycle, and Zband Zcare, independently, H or CH3, and p is 0. In some embodiments Rztogether with Zaforms a 4-5 membered N-heterocycle substituted with 2 CH3, and Zband Zcare, independently, H, and p is 0. In some embodiments Rztogether with Zaforms a 4-5 membered N-heterocycle, and Zband Zcare, independently, H or C3-C6 carbocycle, and wherein p is 0. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, and wherein Zband Zctogether form a C3-C6carbocycle or a 4-6 membered heterocycle. In some embodiments Rztogether with Zaforms a 4-5 membered N-heterocycle, and Zband Zctogether form a C3-C4 carbocycle. In some embodiments Rztogether with Zaforms a 5 membered N-heterocycle, and Zband Zctogether form a C3carbocycle. In some embodiments disclosed Rztogether with Zaforms a 5 membered N-heterocycle, and Zband Zctogether form a C4 carbocycle. In some embodiments Rztogether with Zaforms a 4 membered N-heterocycle, and wherein Zband Zctogether form a C4carbocycle. In some embodiments, the 4-5 membered N- heterocycle is pyrrolidinyl. In some embodiments, the 4-5 membered N-heterocycle is azetidinyl. In some embodiments Rztogether with Zaforms a 4-5 membered N-heterocycle, and Zband Zctogether form a 4 membered O-heterocycle. In some embodiments, the 4-5 membered N- heterocycle is pyrrolidinyl. In some embodiments, the 4-5 membered N-heterocycle is azetidinyl. In some embodiments, the 4 membered O-heterocycle is oxetanyl. In some embodiments, the 4-5 membered N-heterocycle is pyrrolidinyl and the 4 membered O-heterocycle is oxetanyl. In some embodiments, the 4-5 membered N-heterocycle is azetidinyl and the 4 membered O-heterocycle is oxetanyl. In some embodiments Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3alkyl, and Zband Zctogether form a C3-C6carbocycle or a 4-6 membered heterocycle, and p is 0. In some embodiments Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, and Zband Zctogether form a C3-C6 carbocycle or a 4-6 membered heterocycle, and p is 1. In some embodiments Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, and Zband Zctogether form a C3-C6 carbocycle or a 4-6 membered heterocycle, and p is 2. In some embodiments Rztogether with Zaforms a 4-5 membered N-heterocycle, and Zband Zctogether form a C3-C4carbocycle, and p is 0. In some embodiments Rztogether with Zaforms a 4-5 membered N-heterocycle, and Zband Zctogether form a C3-C4 carbocycle, and p is 1. In some embodiments Rztogether with Zaforms a 4-5 membered N-heterocycle, and Zband Zctogether form a 4 membered O-heterocycle, and p is 0. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, and wherein Zbtogether with Rzand Zaform a 7-membered heterobicyclic ring system containing a bridge of 2 carbon atoms, and Zcis H. In some embodiments Rztogether with Zaforms a 4-6 membered N- heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, and Zbtogether with Rzand Zaform a heterobicyclic ring , and Zc is H.In some with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, and Zbtogether with Rzand Zaform a heterobicyclic ring system , Zcis H, and p is 0. In some embodiments disclosed herein is provided a compound of formula (I), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein, R1and R2are each, independently, H or halo; Q1and Q3are each, independently, CH; Q2is C-L-Rbwherein L is O; Rbis a C1-C7alkyl, wherein one or two methylene groups from the C1-C7alkyl is optionally independently replaced with NRe, and wherein the C1-C7 alkyl is optionally substituted with carboxy or 3-10 membered heterocycle, Reis C1-C8alkyl; X is a C1-C4 alkylene; Y is a phenyl or 5-6 membered heteroaryl, wherein the phenyl or 5-6 membered heteroaryl is optionally substituted with 1 to 3 substituents independently selected from halo and C1-C3 alkyl; G is N or CH; Gb is N; Ga is CR5; ; Rzis H, C1-C3 alkyl, or Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4- 6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3alkyl, and: when Rzis H or C1-C3 alkyl: (i) Zaand Zbare, independently, H, C1-C5 alkyl, or halo, wherein the C1-C5 alkyl is optionally substituted with hydroxy, or Zaand Zbtogether form a saturated C3- C6 carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3 alkoxy, and C1-C3 alkyl optionally substituted with hydroxy, or Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, C1-C3 alkyl, halo, hydroxy, C1-C3 alkoxy, C2-C5 alkoxyalkyl, C3-C6 carbocycle, 5-6 membered heteroaryl, or phenyl, wherein the C1-C3alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide, or (ii) Za, Zband Zctogether form a 5-membered bicyclic ring system containing a bridge of 1 carbon atom; when Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3alkyl: Zband Zcare, independently, H, C1-C3 alkyl, or C3-C6 carbocycle, or Zband Zctogether form a C3-C6 carbocycle or a 4-6 membered heterocycle, or Zbtogether with Rzand Zaform a 7-membered heterobicyclic ring system containing a bridge of 2 carbon atoms, and Zcis H. In some embodiments disclosed herein is provided a compound of formula (I) having the structure of formula (I-A): or any stereoisomer thereof, wherein, R1and R2are each, independently, H or halo; Rbis a C1-C7 alkyl, wherein one or two methylene groups from the C1-C7 alkyl is optionally independently replaced with NRe, and wherein the C1-C7alkyl is optionally substituted with carboxy or 3-10 membered heterocycle, Reis C1-C8 alkyl; X is a C1-C4alkylene; Y is a phenyl or 5-6 membered heteroaryl, wherein the phenyl or 5-6 membered heteroaryl is optionally substituted with 1 to 3 substituents independently selected from halo and C1-C3 alkyl; G is N or CH; Rz, Za, Zb, Zcand p are as defined in formula (I). In some embodiments disclosed herein is provided a compound of formula (I) having the structure of formula (I-B): or any thereof, wherein, R1and R2are each, independently, H or halo; Rbis a C1-C7alkyl, wherein the C1-C7alkyl is substituted with a 3-10 membered N-heterocycle, G is N or CH; Rz, Za, Zb, Zcand p are as defined in formula (I). In some embodiments disclosed herein is provided a compound of formula (I-B), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rbis a C1-C7alkyl, wherein the C1-C7 alkyl is substituted with piperazinyl. In some embodiments disclosed herein is provided a compound of formula (I-B) having the structure of formula (I-C): or any In some embodiments disclosed herein is provided a compound of formula (I-B), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H or C1-C3alkyl, and optionally wherein the compound of formula (I-B) has the structure of formula (I-C). In some embodiments disclosed herein is provided a compound of formula (I-B), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H or C1-C3 alkyl, and wherein: Zaand Zbare, independently, H, C1-C5 alkyl, or halo, wherein the C1-C5 alkyl is optionally substituted with hydroxy, or Zaand Zbtogether form a saturated C3-C6 carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3 alkoxy, and C1-C3 alkyl optionally substituted with hydroxy, or Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, C1-C3 alkyl, halo, hydroxy, C1-C3 alkoxy, C2-C5 alkoxyalkyl, C3-C6 carbocycle, 5-6 membered heteroaryl, or phenyl, wherein the C1-C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3amide, and optionally wherein the compound of formula (I-B) has the structure of formula (I-C). In some embodiments Rzis H or C1-C3 alkyl, and wherein Zaand Zbare, independently, H, C1-C5alkyl, or halo, and wherein Zcis hydroxy, C2-C5alkoxyalkyl, or C1-C3alkyl, wherein the C1-C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide, and optionally wherein the compound of formula (I-B) has the structure of formula (I-C). In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbare, independently, H, C1-C5alkyl, or halo, and Zcis C1-C3 alkyl, wherein the C1-C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide, and optionally wherein the compound of formula (I-B) has the structure of formula (I-C). In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbare, independently, H or C1-C5 alkyl, wherein the C1-C5 alkyl is optionally substituted with hydroxy, and Zcis C3-C6 carbocycle, and optionally wherein the compound of formula (I-B) has the structure of formula (I-C). In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbare, independently, H or C1-C3 alkyl, wherein the C1-C3 alkyl is optionally substituted with hydroxy, and Zcis C3 carbocycle, and optionally wherein the compound of formula (I-B) has the structure of formula (I-C). In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbare, independently, H or C1-C5alkyl, and Zcis 5-6 membered heteroaryl, or phenyl, and optionally wherein the compound of formula (I-B) has the structure of formula (I-C). In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbare, independently, H or CH3, and Zcis thiazolyl or phenyl, and optionally wherein the compound of formula (I-B) has the structure of formula (I-C). In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbtogether form a saturated C3- C6 carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3 alkoxy, and C1-C3 alkyl optionally substituted with hydroxy, and Zcis H, halo, C1- C3alkoxy, or C1-C3alkyl optionally substituted with hydroxy or halo, and optionally wherein the compound of formula (I-B) has the structure of formula (I-C). In some embodiments disclosed herein is provided a compound of formula (I) having the structure of formula (I-D): or any thereof, wherein, R1and R2are each, independently, H or halo; Rbis a C1-C7 alkyl, wherein the C1-C7 alkyl is substituted with a 3-10 membered N-heterocycle; G is N or CH; Rz, Za, Zb, Zcand p are as defined in formula (I). In some embodiments disclosed herein is provided a compound of formula (I-D), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rbis a C1-C7 alkyl, wherein the C1-C7 alkyl is substituted with piperazinyl. In some embodiments disclosed herein is provided a compound of formula (I-D) having the structure of formula (I-E):

[0003] E) or any stereoi ereof, wherein, R1and R2are each, independently, H or halo; G is N or CH; Rz, Za, Zb, Zcand p are as defined in formula (I). In some embodiments disclosed herein is provided a compound of formula (I-D), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H or C1-C3 alkyl, and optionally wherein the compound of formula (I-D) has the structure of formula (I-E). In some embodiments disclosed herein is provided a compound of formula (I-D), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H or C1-C3alkyl, and wherein: Zaand Zbare, independently, H, C1-C5 alkyl, or halo, wherein the C1-C5 alkyl is optionally substituted with hydroxy, or Zaand Zbtogether form a saturated C3-C6carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3 alkoxy, and C1-C3 alkyl optionally substituted with hydroxy, or Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, C1-C3 alkyl, halo, hydroxy, C1-C3 alkoxy, C2-C5 alkoxyalkyl, C3-C6 carbocycle, 5-6 membered heteroaryl, or phenyl, wherein the C1-C3alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3amide, and optionally wherein the compound of formula (I-D) has the structure of formula (I-E). In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbare, independently, H, C1-C5 alkyl, or halo, and Zcis hydroxy, C2-C5alkoxyalkyl, or C1-C3alkyl, wherein the C1-C3alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1- C4 alkylamino, and C1-C3 amide, and optionally wherein the compound of formula (I-D) has the structure of formula (I-E). In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbare, independently, H, C1-C5alkyl, or halo, and Zcis C1-C3 alkyl, wherein the C1-C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide, and optionally wherein the compound of formula (I-D) has the structure of formula (I-E). In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbare, independently, H or C1-C5 alkyl, wherein the C1-C5 alkyl is optionally substituted with hydroxy, and Zcis C3-C6 carbocycle, and optionally wherein the compound of formula (I-D) has the structure of formula (I-E). In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbare, independently, H or C1-C3 alkyl, wherein the C1-C3 alkyl is optionally substituted with hydroxy, and Zcis C3 carbocycle, and optionally wherein the compound of formula (I-D) has the structure of formula (I-E). In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbare, independently, H or C1-C5alkyl, and Zcis 5-6 membered heteroaryl, or phenyl, and optionally wherein the compound of formula (I-D) has the structure of formula (I-E). In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbare, independently, H or CH3, and Zcis thiazolyl or phenyl, and optionally wherein the compound of formula (I-D) has the structure of formula (I-E). In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbtogether form a saturated C3- C6 carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3 alkoxy, and C1-C3 alkyl optionally substituted with hydroxy, and Zcis H, halo, C1- C3alkoxy, or C1-C3alkyl optionally substituted with hydroxy or halo, and optionally wherein the compound of formula (I-D) has the structure of formula (I-E). In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, and optionally wherein the compound of formula (I-D) has the structure of formula (I-E). In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, wherein the 4-6 membered heterocycle contains O or S, and Zcis H, and optionally wherein the compound of formula (I-D) has the structure of formula (I-E). In some embodiments Rzis H or C1-C3alkyl, and Za, Zband Zctogether form a 5-membered bicyclic ring system containing a bridge of 1 carbon atom, and optionally wherein the compound of formula (I-D) has the structure of formula (I-E). In some embodiments Rzis H or C1-C3alkyl, and Za, Zband Zctogether form the bicyclicring , and optionally wherein the compound of formula (I-D) has the structureof formula In some embodiments Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3alkyl, and optionally wherein the compound of formula (I-D) has the structure of formula (I-E). In some embodiments Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, and Zband Zcare, independently, H, C1-C3 alkyl, or C3-C6 carbocycle, and optionally wherein the compound of formula (I-D) has the structure of formula (I-E). In some embodiments Rztogether with Zaforms a 4-5 membered N-heterocycle optionally substituted with 1 or 2 CH3, and Zband Zcare, independently, H, CH3, or C3carbocycle, and optionally wherein the compound of formula (I-D) has the structure of formula (I-E). In some embodiments Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, and Zband Zctogether form a C3-C6 carbocycle or a 4-6 membered heterocycle, and optionally wherein the compound of formula (I-D) has the structure of formula (I-E). In some embodiments Rztogether with Zaforms a 4-5 membered N-heterocycle, and Zband Zctogether form a C3-C4 carbocycle, and optionally wherein the compound of formula (I-D) has the structure of formula (I-E). In some embodiments Rztogether with Zaforms a 4-5 membered N-heterocycle, and Zband Zctogether form a 4 membered O-heterocycle, and optionally wherein the compound of formula (I-D) has the structure of formula (I-E). In some embodiments Zbtogether with Rzand Zaform a 7-membered heterobicyclic ring system containing a bridge of 2 carbon atoms, and Zcis H, and optionally wherein the compound of formula (I-D) has the structure of formula (I-E). In some embodiments Zbtogether with Rzand Zaform the heterobicyclic ring system: optionally wherein the compound of formula (I-D) has the structure In some embodiments disclosed herein is provided a compound of formula (I) having the structure of formula (I-F):

[0004] F) or any stereoisome salt thereof, wherein, R1and R2are each, independently, H or halo; Rbis a C1-C7 alkyl, wherein one methylene group from the C1-C7 alkyl is replaced with -N(CH3)- ; G is N or CH; Rz, Za, Zb, Zcand p are as defined in formula (I). In some embodiments disclosed herein is provided a compound of formula (I-F) having the structure of formula (I-G):

[0005] or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein, R1and R2are each, independently, H or halo; G is N or CH; Rz, Za, Zb, Zcand p are as defined in formula (I). In some embodiments disclosed herein is provided a compound of formula (I-F), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H or C1-C3 alkyl, and optionally wherein the compound of formula (I-F) has the structure of formula (I-G). In some embodiments disclosed herein is provided a compound of formula (I-F), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H or C1-C3alkyl, and wherein: Zaand Zbare, independently, H, C1-C5 alkyl, or halo, wherein the C1-C5 alkyl is optionally substituted with hydroxy, or Zaand Zbtogether form a saturated C3-C6carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3 alkoxy, and C1-C3 alkyl optionally substituted with hydroxy, or Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, C1-C3 alkyl, halo, hydroxy, C1-C3 alkoxy, C2-C5 alkoxyalkyl, C3-C6 carbocycle, 5-6 membered heteroaryl, or phenyl, wherein the C1-C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide, and optionally wherein the compound of formula (I-F) has the structure of formula (I-G). In some embodiments Rzis H or C1-C3alkyl, and wherein Zaand Zbare, independently, H, C1-C5 alkyl, or halo, and Zcis hydroxy, C2-C5 alkoxyalkyl, or C1-C3 alkyl, wherein the C1-C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4alkylamino, and C1-C3amide, and optionally wherein the compound of formula (I-F) has the structure of formula (I-G). In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbare, independently, H, C1-C5 alkyl, or halo, and Zcis C1-C3alkyl, wherein the C1-C3alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide, and optionally wherein the compound of formula (I-F) has the structure of formula (I-G). In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbare, independently, H or C1-C5 alkyl, wherein the C1-C5 alkyl is optionally substituted with hydroxy, and Zcis C3-C6 carbocycle, and optionally wherein the compound of formula (I-F) has the structure of formula (I-G). In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbare, independently, H or C1-C3 alkyl, wherein the C1-C3 alkyl is optionally substituted with hydroxy, and Zcis C3 carbocycle, and optionally wherein the compound of formula (I-F) has the structure of formula (I-G). In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbare, independently, H or C1-C5alkyl, and Zcis 5-6 membered heteroaryl, or phenyl, and optionally wherein the compound of formula (I-F) has the structure of formula (I-G). In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbare, independently, H or CH3, and Zcis thiazolyl or phenyl, and optionally wherein the compound of formula (I-F) has the structure of formula (I-G). In some embodiments disclosed herein is provided a compound of formula (I) having the structure of formula (I-H): or any thereof, wherein, R1and R2are each, independently, H or halo; Rbis a C1-C7alkyl, wherein the C1-C7alkyl is substituted with carboxy; G is N or CH; Rz, Za, Zb, Zcand p are as defined in formula (I). In some embodiments disclosed herein is provided a compound of formula (I-H) having the structure of formula (I-I): I) or any wherein, R1and R2are each, independently, H or halo; G is N or CH; Rz, Za, Zb, Zcand p are as defined in formula (I). In some embodiments disclosed herein is provided a compound of formula (I-H), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H or C1-C3 alkyl, and optionally wherein the compound of formula (I-H) has the structure of formula (I-I). In some embodiments disclosed herein is provided a compound of formula (I-H) or a compound of formula (I-H), or any stereoisomer thereof or pharmaceutically acceptable salt thereof, wherein Rzis H or C1-C3 alkyl, and wherein: Zaand Zbare, independently, H, C1-C5 alkyl, or halo, wherein the C1-C5 alkyl is optionally substituted with hydroxy, or Zaand Zbtogether form a saturated C3-C6carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3 alkoxy, and C1-C3 alkyl optionally substituted with hydroxy, or Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, C1-C3 alkyl, halo, hydroxy, C1-C3 alkoxy, C2-C5 alkoxyalkyl, C3-C6 carbocycle, 5-6 membered heteroaryl, or phenyl, wherein the C1-C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4alkylamino, and C1-C3 amide, and optionally wherein the compound of formula (I-H) has the structure of formula (I-I). In some embodiments Rzis H or C1-C3alkyl, and Zaand Zbare, independently, H, C1-C5alkyl, or halo, and Zcis hydroxy, C2-C5 alkoxyalkyl, or C1-C3 alkyl, wherein the C1-C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1- C4alkylamino, and C1-C3amide, and optionally wherein the compound of formula (I-H) has the structure of formula (I-I). In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbare, independently, H, C1-C5 alkyl, or halo, and Zcis C1-C3alkyl, wherein the C1-C3alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4alkylamino, and C1-C3amide, and optionally wherein the compound of formula (I-H) has the structure of formula (I-I). In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbare, independently, H or C1-C5 alkyl, wherein the C1-C5alkyl is optionally substituted with hydroxy, and Zcis C3-C6carbocycle, and optionally wherein the compound of formula (I-H) has the structure of formula (I-I). In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbare, independently, H or C1-C3 alkyl, wherein the C1-C3alkyl is optionally substituted with hydroxy, and Zcis C3carbocycle, and optionally wherein the compound of formula (I-H) has the structure of formula (I-I). In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbare, independently, H or C1-C5 alkyl, and Zcis 5-6 membered heteroaryl, or phenyl, and optionally wherein the compound of formula (I-H) has the structure of formula (I-I). In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbare, independently, H or CH3, and Zcis thiazolyl or phenyl, and optionally wherein the compound of formula (I-H) has the structure of formula (I-I). In some embodiments Rzis H or C1-C3 alkyl, and Zaand Zbtogether form a saturated C3- C6carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3 alkoxy, and C1-C3 alkyl optionally substituted with hydroxy, and Zcis H, halo, C1- C3 alkoxy, or C1-C3 alkyl optionally substituted with hydroxy or halo, and optionally wherein the compound of formula (I-H) has the structure of formula (I-I). In some embodiments Rzis H or C1-C3alkyl, and Za, Zband Zctogether form a 5-membered bicyclic ring system containing a bridge of 1 carbon atom, and optionally wherein the compound of formula (I-H) has the structure of formula (I-I). In some embodiments Rzis H or C1-C3alkyl, and Za, Zband Zctogether form the bicyclicring , and optionally wherein the compound of formula (I-H) has the structureof formula In some embodiments Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3alkyl, and optionally wherein the compound of formula (I-H) has the structure of formula (I-I). In some embodiments Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, and Zband Zcare, independently, H, C1-C3 alkyl, or C3-C6 carbocycle, and optionally wherein the compound of formula (I-H) has the structure of formula (I-I). In some embodiments Rztogether with Zaforms a 4-5 membered N-heterocycle optionally substituted with 1 or 2 CH3, and Zband Zcare, independently, H, CH3, or C3carbocycle, and optionally wherein the compound of formula (I-H) has the structure of formula (I-I). In some embodiments Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, and Zband Zctogether form a C3-C6 carbocycle or a 4-6 membered heterocycle, and optionally wherein the compound of formula (I-H) has the structure of formula (I-I). In some embodiments Rztogether with Zaforms a 4-5 membered N-heterocycle, and Zband Zctogether form a C3-C4 carbocycle, and optionally wherein the compound of formula (I-H) has the structure of formula (I-I). In some embodiments Rztogether with Zaforms a 4-5 membered N-heterocycle, and Zband Zctogether form a 4 membered O-heterocycle, and optionally wherein the compound of formula (I-H) has the structure of formula (I-I). In some embodiments disclosed herein is provided a compound selected from: 9-Benzyl-N-(tert-butyl)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9H-purin-6-amine; N-(tert-butyl)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; N-(tert-butyl)-2-(2-chloro-4-(2-(dimethylamino)ethoxy)phenyl)-1-((4-methylpyridin-2- yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine; 4-(4-(6-(Tert-butylamino)-9-(3-chlorobenzyl)-9H-purin-8-yl)-3-chlorophenoxy)-2- methylbutanoic acid; 9-benzyl-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(1-methylcyclopropyl)-9H-purin-6- amine; 9-benzyl-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(1-methylcyclobutyl)-9H-purin-6- amine; N-(tert-butyl)-8-(2-chloro-4-(2-(dimethylamino)ethoxy)phenyl)-N-methyl-9-((4-methylpyridin- 2-yl)methyl)-9H-purin-6-amine; 4-(3-chloro-4-(9-(3-chlorobenzyl)-6-(2,2-dimethylpyrrolidin-1-yl)-9H-purin-8-yl)phenoxy)-2- methylbutanoic acid; 4-(3-chloro-4-(9-(3-chlorobenzyl)-6-(2,2-dimethylazetidin-1-yl)-9H-purin-8-yl)phenoxy)-2- methylbutanoic acid; 4-(3-chloro-4-(9-(3-chlorobenzyl)-6-(4-azaspiro[2.4]heptan-4-yl)-9H-purin-8-yl)phenoxy)-2- methylbutanoic acid; 5 4-(3-chloro-4-(9-(3-chlorobenzyl)-6-(1-azaspiro[3.3]heptan-1-yl)-9H-purin-8-yl)phenoxy)-2- methylbutanoic acid; 4-(3-chloro-4-(9-(3-chlorobenzyl)-6-((1-methylcyclobutyl)amino)-9H-purin-8-yl)phenoxy)-2- methylbutanoic acid; 4-(4-(6-(bicyclo[1.1.1]pentan-1-ylamino)-9-(3-chlorobenzyl)-9H-purin-8-yl)-3-chlorophenoxy)- 10 2-methylbutanoic acid; 4-(4-(6-(tert-butyl(methyl)amino)-9-(3-chlorobenzyl)-9H-purin-8-yl)-3-chlorophenoxy)-2- methylbutanoic acid; 4-(3-chloro-4-(9-(3-chlorobenzyl)-6-(5-azaspiro[3.4]octan-5-yl)-9H-purin-8-yl)phenoxy)-2- methylbutanoic acid; 15 4-(3-chloro-4-(9-(3-chlorobenzyl)-6-(6-oxa-1-azaspiro[3.3]heptan-1-yl)-9H-purin-8- yl)phenoxy)-2-methylbutanoic acid; 4-(3-chloro-4-(9-(3-chlorobenzyl)-6-(2-oxa-5-azaspiro[3.4]octan-5-yl)-9H-purin-8-yl)phenoxy)- 2-methylbutanoic acid; 4-(3-chloro-4-(9-(3-chlorobenzyl)-6-((1-methylcyclopropyl)amino)-9H-purin-8-yl)phenoxy)-2- 20 methylbutanoic acid; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-cyclohexyl-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-6-(3,3-dimethylazetidin-1-yl)-9-((4- methylpyridin-2-yl)methyl)-9H-purine; 25 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(3,3-dimethylbutyl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; (S)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-N- (tetrahydrofuran-3-yl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-((1-fluorocyclobutyl)methyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 5 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-N- ((tetrahydrofuran-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N,N-diethyl-9-((4-methylpyridin-2-yl)methyl)- 9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-N- 10 (tetrahydro-2H-pyran-4-yl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(cyclopropylmethyl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; (1-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-9H- purin-6-yl)amino)cyclopentyl)methanol; 15 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-cyclobutyl-N-methyl-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(3,3-difluorocyclobutyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-cyclopropyl-N-ethyl-9-((4-methylpyridin-2- 20 yl)methyl)-9H-purin-6-amine; (S)-3-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-9H- purin-6-yl)amino)-2-methylbutan-2-ol; (1-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-9H- purin-6-yl)amino)cyclopropyl)methanol; 25 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(2-fluoro-2-methylpropyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(1-methylcyclobutyl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-6-(3,3-dimethylpyrrolidin-1-yl)-9-((4- methylpyridin-2-yl)methyl)-9H-purine; 5 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-((1-(fluoromethyl)cyclopropyl)methyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; (S)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(3,3-dimethylbutan-2-yl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; (1S,3R)-3-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)- 10 9H-purin-6-yl)amino)cyclopentan-1-ol; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-6-(2,2-dimethylpyrrolidin-1-yl)-9-((4- methylpyridin-2-yl)methyl)-9H-purine; (R)-2-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-9H- purin-6-yl)amino)-2-cyclopropylethan-1-ol; 15 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(cyclopropylmethyl)-N-methyl-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(cyclobutylmethyl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-((1-methylcyclobutyl)methyl)-9-((4- 20 methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-cyclobutyl-9-((4-methylpyridin-2-yl)methyl)- 9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-6-(5- azaspiro[2.4]heptan-5-yl)-9H-purine; 25 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-6-(5- azaspiro[2.4]heptan-5-yl)-9H-purine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(cyclobutylmethyl)-N-methyl-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(2-cyclopropylethyl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; 5 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-cyclopentyl-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(2-cyclobutylethyl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; N-(bicyclo[1.1.1]pentan-1-yl)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4- 10 methylpyridin-2-yl)methyl)-9H-purin-6-amine; 1-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-9H-purin- 6-yl)amino)-2-methylpropan-2-ol; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(2,2-difluoropropyl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; 15 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-((1s,3s)-3-methoxycyclobutyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; (3-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-9H- purin-6-yl)amino)cyclobutyl)methanol; (R)-2-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-9H- 20 purin-6-yl)amino)butan-1-ol; (R)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-N- (tetrahydrofuran-3-yl)-9H-purin-6-amine; (R)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-6-(2- methylpyrrolidin-1-yl)-9H-purine; 25 (S)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-6-(2-cyclopropylpyrrolidin-1-yl)-9-((4- methylpyridin-2-yl)methyl)-9H-purine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-((1-methoxycyclopropyl)methyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(3-fluorocyclobutyl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; 5 (R)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-6-(2-cyclopropylpyrrolidin-1-yl)-9-((4- methylpyridin-2-yl)methyl)-9H-purine; (S)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-N- (tetrahydro-2H-pyran-3-yl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(1-methoxy-2-methylpropan-2-yl)-9-((4- 10 methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(1-cyclopropylethyl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-6-(3-methylazetidin-1-yl)-9-((4-methylpyridin- 2-yl)methyl)-9H-purine; 15 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-cyclopropyl-N-methyl-9-((4-methylpyridin- 2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(3,3-dimethylbutan-2-yl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-N-(thiazol-5- 20 ylmethyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-N-(thiazol-2- ylmethyl)-9H-purin-6-amine; (R)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-N-(1- phenylethyl)-9H-purin-6-amine; 25 2-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-9H-purin- 6-yl)amino)-N,N-dimethylacetamide; (R)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(1-cyclopropylethyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; N-(2-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-9H- purin-6-yl)amino)ethyl)acetamide; 5 6-(7-azabicyclo[2.2.1]heptan-7-yl)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purine; 3-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-9H-purin- 6-yl)amino)thietane 1,1-dioxide; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(cyclopentylmethyl)-9-((4-methylpyridin-2- 10 yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-((1-methylcyclopropyl)methyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(2-ethylbutyl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; 15 and pharmaceutically acceptable salts thereof. It is to be understood that any of definitions, claims, aspects or embodiments of the variable groups of the formulae disclosed herein, may be combined with any other definitions, claims, aspects or embodiments herein (unless the context does not permit) to provide further 20 embodiments of the specification. Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and organic acids, e.g., acetate, aspartate, benzoate, besylate, bromide / hydrobromide, bicarbonate / carbonate, bisulfate / sulfate, camphorsulfonate, chloride / hydrochloride, chlortheophyllonate, citrate, ethanedisulfonate, fumarate, gluceptate, gluconate, glucuronate, 25 hippurate, hydroiodide / iodide, isethionate, lactate, lactobionate, laurylsulfate, malate, maleate, malonate, mandelate, mesylate, methylsulfate, naphthoate, napsylate, nicotinate, nitrate, octadecanoate, oleate, oxalate, palmitate, palmoate, phosphate / hydrogen phosphate / dihydrogen phosphate, polygalacturonate, propionate, stearate, succinate, subsalicylate, sulfate / hydrogensulfate, tartrate, tosylate and trifluoroacetate salts. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, oxalic acid, maleic acid, malonic acid, succinic 5 acid, fumaric acid, tartaric acid, citric acid, benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, toluenesulfonic acid, trifluoroacetic acid, sulfosalicylic acid, and the like. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases. Inorganic bases from which salts can be derived include, for example, ammonia and salts of ammonium and metals from columns I to XII of the periodic table. In certain embodiments, the 10 salts are derived from sodium, potassium, ammonium, calcium, magnesium, iron, silver, zinc, and copper; particularly suitable salts include ammonium, potassium, sodium, calcium and magnesium salts. Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, and the like. Certain organic amines include isopropylamine, 15 benzathine, cholinate, diethanolamine, diethylamine, lysine, meglumine, piperazine and tromethamine. The pharmaceutically acceptable salts of the compounds disclosed herein can be synthesized from a basic or acidic moiety, by conventional chemical methods. Generally, such salts can be prepared by reacting free acid forms of these compounds with a stoichiometric amount 20 of the appropriate base (such as Na+, Ca2+, Mg2+, or K+hydroxide, carbonate, bicarbonate or the like), or by reacting free base forms of these compounds with a stoichiometric amount of the appropriate acid. Such reactions are typically carried out in water or in an organic solvent, or in a mixture of the two. Generally, use of non-aqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile is desirable, where practicable. Lists of additional suitable salts can be 25 found, e.g., in “Remington's Pharmaceutical Sciences,” 20th ed., Mack Publishing Company, Easton, Pa., (1985); Berge et al., "J. Pharm. Sci., 1977, 66, 1-19 and in “Handbook of Pharmaceutical Salts: Properties, Selection, and Use” by Stahl and Wermuth (Wiley-VCH, Weinheim, Germany, 2002). It is also to be understood that certain compounds disclosed herein, and pharmaceutically 30 salts thereof, can exist in solvated as well as unsolvated forms such as, for example, hydrated and anhydrous forms. It is to be understood that the compounds herein encompass all such solvated forms. For the sake of clarity, this includes both solvated (e.g., hydrated) forms of the free form of the compound, as well as solvated (e.g., hydrated) forms of the salt of the compound. Any formula given herein is also intended to represent unlabeled forms as well as 5 isotopically labeled forms for the compounds disclosed herein. Isotopically labeled compounds have structures depicted by the formulas given herein except that one or more atoms are replaced by an atom of the same element but with differing mass number. Examples of isotopes that can be incorporated into the compounds disclosed herein and their pharmaceutically acceptable salts include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine, chlorine 10 and iodine, such as2H,3H,11C,13C,14C,15N,35S,36Cl and125I. Isotopically labeled compounds disclosed herein can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described in the accompanying Examples using appropriate isotopically labeled reagents in place of the non-labeled reagents previously employed. The compounds disclosed herein may have different isomeric forms. The language “optical 15 isomer,” “stereoisomer” “enantiomer” or “diastereoisomer” refers to any of the various stereoisomeric configurations which may exist for a given compound disclosed herein. Likewise, it is understood that the compounds disclosed herein may exist in tautomeric forms other than that shown in the formula and these are also included within the scope of the present specification. It is understood that a substituent may be attached at a chiral center of a carbon atom and, therefore, 20 the disclosed compounds include enantiomers, diastereomers and racemates. The term “enantiomer” includes pairs of stereoisomers that are non-superimposable mirror images of each other. A 1:1 mixture of a pair of enantiomers is a racemic mixture. The (+ / -) term is used to designate a racemic mixture where appropriate. The terms “diastereomers” or “diastereoisomers” include stereoisomers that have at least two asymmetric atoms, but which are not mirror images of 25 each other. The absolute stereochemistry is specified according to the Cahn-Ingold-Prelog R-S system. When a compound is a pure enantiomer, the stereochemistry at each chiral center may be specified by either R or S. It is understood that one of skill in the art could determine optical rotation and / or absolute stereochemistry. It is understood that such a disclosure includes other stereoisomeric forms of the 30 same compound, as well as stereoisomeric mixtures. Certain compounds disclosed herein contain one or more asymmetric centers or axes and may thus give rise to enantiomers, diastereomers or other stereoisomeric forms that may be defined, in terms of absolute stereochemistry, as (R)- or (S)-. The present disclosure is meant to include all such possible isomers, including racemic mixtures, optically pure forms and intermediate mixtures. Optically active (R)- and (S)-isomers 5 may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques well known in the art, such as chiral HPLC. Pharmaceutical Compositions In some embodiments, disclosed are pharmaceutical compositions comprising a compound 10 disclosed herein and a pharmaceutically acceptable excipient. In some embodiments, disclosed are pharmaceutical compositions comprising a compound disclosed herein and a pharmaceutically acceptable carrier. The language “pharmaceutically acceptable carrier” and “pharmaceutically acceptable excipient” includes compounds, materials, compositions, and / or dosage forms which are, within 15 the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, as ascertained by one of skill in the art. For example, "pharmaceutically acceptable" as used herein includes compounds approved by a regulatory agency of the Federal or a state government, or listed in the U.S. Pharmacopeia, European Pharmacopeia or other generally 20 recognized pharmacopeia for use in animals, and more particularly in humans. The disclosed compositions may be in a form suitable for oral use, for topical use, for administration by inhalation, for administration by insufflation or for parenteral administration. The amount of active ingredient that is combined with one or more pharmaceutically acceptable carriers to produce a single dosage form will necessarily vary depending upon the host 25 treated and the particular route of administration. For further information on Routes of Administration and Dosage Regimes the reader is referred to Chapter 25. 3 in Volume 5 of Comprehensive Medicinal Chemistry (Corwin Hansch; Chairman of Editorial Board), Pergamon Press 1990. The pharmaceutical formulations of the compounds disclosed herein may conveniently be administered in unit dosage form and may be prepared by any of the methods well-known in the pharmaceutical art, for example as described in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, PA. , (1985). 5 Pharmaceutical formulations suitable for oral administration may comprise one or more physiologically compatible carriers and / or excipients and may be in solid or liquid form. Therapeutic Utilities In some embodiments, there is provided a method of treating cancer in a subject in need 10 thereof comprising administering a therapeutically effective amount of a compound of Formula (I) optionally wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In some embodiments, there is provided a compound of Formula (I) optionally wherein the 15 compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for use in treating cancer in a subject in need thereof. In some embodiments, there is provided use of a compound of Formula (I) optionally wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed 20 herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof in the manufacture of a medicament for the treatment of cancer in a subject in need thereof. In certain embodiments, the cancer exhibits homologous recombination repair deficiency (HRD). 25 In some embodiments, the cancer is a solid cancer, such as breast, ovarian, pancreatic, or prostate cancer. In certain embodiments, the cancer is a breast, ovarian, pancreatic, or prostate cancer comprising a BRCA1 and / or BRCA2 mutation. In other embodiments, the cancer is a breast, ovarian, pancreatic, or prostate cancer comprising a BRCA1 mutation. In still other embodiments, the cancer is a breast, ovarian, pancreatic, or prostate cancer comprising a BRCA2 mutation. In some embodiments, the cancer is breast cancer. In further embodiments, the cancer is BRCA1 and / or BRCA2-positive breast cancer. In other embodiments, the cancer is BRCA1- 5 positive breast cancer. In still other embodiments, the cancer is BRCA2-positive breast cancer. In some embodiments, the cancer is ovarian cancer. In further embodiments, the cancer is BRCA1 and / or BRCA2-positive ovarian cancer. In other embodiments, the cancer is BRCA1- positive ovarian cancer. In still other embodiments, the cancer is BRCA2-positive ovarian cancer. In some embodiments, the cancer is pancreatic cancer. In further embodiments, the cancer10 is BRCA1 and / or BRCA2-positive pancreatic cancer. In other embodiments, the cancer is BRCA1- positive pancreatic cancer. In still other embodiments, the cancer is BRCA2-positive pancreatic cancer. In some embodiments, the cancer is prostate cancer. In further embodiments, the cancer is BRCA1 and / or BRCA2-positive prostate cancer. In other embodiments, the cancer is BRCA1- 15 positive prostate cancer. In still other embodiments, the cancer is BRCA2-positive prostate cancer. In some embodiments, the cancer is PARP inhibitor (PARPi) resistant. In some embodiments, the PARPi resistant cancer is PARPi-resistant ovarian cancer. In some embodiments, the PARPi resistant cancer is PARPi-resistant breast cancer. In some embodiments, the PARPi resistant cancer is PARPi-resistant prostate cancer. In some embodiments, the PARPi 20 resistant cancer is PARPi-resistant pancreatic cancer. In some embodiments, the method comprises treating a subject with primary and secondary solid tumors. In still other embodiments, the method comprises treating subjects with primary solid tumors. In yet other embodiments, the method comprises treating subjects with secondary solid tumors. 25 In some embodiments, the cancer is Ataxia Telangiectasia Mutated (ATM) mutation- positive. In certain embodiments, the ATM mutation-positive cancer is a hematological cancer, such as leukemia or lymphoma. In certain embodiments, the ATM mutation-positive cancer is acute leukemia, chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). In other embodiments, the ATM mutation-positive cancer is a solid cancer. In certain embodiments, the ATM mutation-positive cancer is lung cancer, gastric cancer, stomach cancer, breast cancer, ovarian cancer, colorectal cancer, melanoma, or sarcoma. In some embodiments, the cancer is positive for a mutation in genes coding for Fanconi anemia (FA) proteins or FA-like genes, including FANCA, FANCB, FANCC, FANCD1 5 (BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANJ (BRIP1), FANCL, FANCM, FANCN (PALB2), FANCP (SLX4), and FANCS (BRCA1). In some embodiments, the cancer is positive for a mutation in genes coding for DNA repair proteins, including RAD50, RAD51, RAD51B, RAD51C, RAD51D, RAD51L1, RAD51L2, RAD51L3, XRCC2, XRCC3, RAD52, RAD54, RAD54L, RAD54B, MRE11, NBS1, DMC1, 10 CTIP (CTBP-interacting Protein), PALB2 (Partner and Localizer of BRCA2), RECQL4 (RecQ Protein-like 4), BLM (Bloom syndrome, RecQ helicase-like), WRN (Werner syndrome, RecQ helicase-like), NBS1 (Nibrin), and EMSY. In some embodiments, the cancer is positive for a mutation in one or more genes associated with the double strand break (DSB) repair pathway, including AICDA, ALKBH3, APOBEC2, 15 APOBEC4, APTX, ATF2, ATM, AURKA, BARD1, BRCA2, BRIP1, CBX3, CCNH, CDC16, CDC25A, CDC25B, CDC45, CDKN1A, CDKN2A, CHEK2, CLK2, CLSPN, CUL4A, CUL5, DCLRE1A, DCLRE1C, DDB1, DKC1, DNMT3A, DNMT3B, DUT, EME2, ENDOV, EP300, ERCC4, ERCC5, FAN1, FANCG, FANCL, FBXO18, FEN1, GADD45A, GINS1, GTF2H2, GTF2H3, GTF2H4, HDAC2, HDAC3, HDAC4, HELQ, INIP, INO80C, KDM4B, LIG3, LMO4, 20 MAD2L2, MBD4, MGMT, MLH1, MNAT1, MPG, MRE11A, MSH2, MSH6, MTBP, MUTYH, NABP1, NBN, NEIL1, NEIL2, NEIL3, NEK1, NHEJ1, NTHL1, ORC6, PALB2, PARP2, PARP3, PAXIP1, PIF1, PMS2, POLB, POLE, POLK, POLL, POLM, POLN, PPP1CA, PRKDC, PRMT2, PROKR1, RAD21, RAD23B, RAD51, RAD51AP1, RAD52, RAD9A, RAD9B, RB1, RECQL4, RECQL5, REV1, RIF1, RINT1, RMI1, RNASEH1, RNASEH2A, RPA1, RPA2, RTEL1, 25 SHPRH, SIRT6, SLX4, SMC5, SMG1, SMUG1, SPO11, SUMO1, SUMO2, SUV39H1, SUV420H2, SWI5, TDG, TELO2, THOC1, TICRR, TNKS, TNKS2, TOP1, TOP2A, TOP3A, TOP3B, TREX2, TRP53BP1, UBE2N, UNG, UVSSA, WRN, XAB2, XRCC2, XRCC3, and / or, XRCC5. 30 Combination Therapy The compounds of Formula (I) optionally wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, may also be administered in conjunction with other compounds used for the treatment of the above conditions. 5 In some embodiments, there is provided a method of treating cancer in a subject in need thereof comprising administering a combination of a therapeutically effective amount of a compound of Formula (I) optionally wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable 10 salt thereof, or a pharmaceutical composition thereof and a second active ingredient, wherein the compound and second active ingredient are administered concurrently, sequentially or in admixture. In some embodiments, there is provided a compound of Formula (I) optionally wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a 15 stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for use in treating cancer in a subject in need thereof in combination with a second active ingredient, wherein the compound and second active ingredient are administered concurrently, sequentially or in admixture. In some embodiments, there is provided use of a compound of Formula (I) optionally 20 wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof in the manufacture of a medicament for the treatment of cancer in a subject in need thereof in combination with a second active ingredient, wherein the compound and second active ingredient are administered concurrently, sequentially or in admixture. 25 In some embodiments, there is provided a method of treating cancer in a subject in need thereof comprising administering a combination of a therapeutically effective amount of a compound of Formula (I) optionally wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable 30 salt thereof, or a pharmaceutical composition thereof and a PARP inhibitor, wherein the compound and second active ingredient are administered concurrently, sequentially or in admixture. In some embodiments, there is provided a compound of Formula (I) optionally wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for use in treating cancer in a subject in need thereof in combination with a PARP inhibitor, 5 wherein the compound and second active ingredient are administered concurrently, sequentially or in admixture. In some embodiments, there is provided use of a compound of Formula (I) optionally wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical 10 composition thereof in the manufacture of a medicament for the treatment of cancer in a subject in need thereof in combination with a PARP inhibitor, wherein the compound and second active ingredient are administered concurrently, sequentially or in admixture. In certain embodiments, the PARP inhibitor is olaparib, AZD9574 (WO 2021 / 260092), saruparib (AZD5305) (WO 2021 / 013735), talazoparib, niraparib, or rucaparib. In other 15 embodiments, the PARP inhibitor is olaparib, AZD9574, or saruparib (AZD5305). In particular embodiments, the cancer is breast, ovarian, pancreatic, or prostate cancer. In certain embodiments, the PARP inhibitor is olaparib and the cancer is breast, ovarian, pancreatic, or prostate cancer. In other embodiments, the PARP inhibitor is niraparib and the cancer is ovarian cancer. In other embodiments, the PARP inhibitor is rucaparib and the cancer is ovarian cancer or prostate cancer. 20 In other embodiments, the PARP inhibitor is talazoparib and the cancer is breast cancer or prostate cancer. In some embodiments, there is provided a method of treating cancer in a subject in need thereof comprising administering a combination of a therapeutically effective amount of a 25 compound of Formula (I) optionally wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof and an ATR inhibitor, wherein the compound and second active ingredient are administered concurrently, sequentially or in admixture. In some embodiments, there is provided a compound of Formula (I) optionally wherein the 30 compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for use in treating cancer in a subject in need thereof in combination with an ATR inhibitor, wherein the compound and second active ingredient are administered concurrently, sequentially or in admixture. In some embodiments, there is provided use of a compound of Formula (I) optionally 5 wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof in the manufacture of a medicament for the treatment of cancer in a subject in need thereof in combination with an ATR inhibitor, wherein the compound and second active ingredient are administered concurrently, sequentially or in admixture. 10 In certain embodiments, the ATR inhibitor is AZD6738 (WO 2011 / 154737). In some embodiments, there is provided a method of treating cancer in a subject in need thereof comprising administering a combination of a therapeutically effective amount of a compound of Formula (I) optionally wherein the compound of formula (I) has the structure of 15 formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof and a DNA-PK inhibitor, wherein the compound and second active ingredient are administered concurrently, sequentially or in admixture. In some embodiments, there is provided a compound of Formula (I) optionally wherein the 20 compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for use in treating cancer in a subject in need thereof in combination with a DNA-PK inhibitor, wherein the compound and second active ingredient are administered concurrently, sequentially or in admixture. 25 In some embodiments, there is provided use of a compound of Formula (I) optionally wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof in the manufacture of a medicament for the treatment of cancer in a subject in need thereof in combination with an DNA-PK inhibitor, wherein the compound and second 30 active ingredient are administered concurrently, sequentially or in admixture. In certain embodiments, the DNA-PK inhibitor is AZD7648 (WO 2018 / 114999). In some embodiments, there is provided a method of treating cancer in a subject in need thereof comprising administering a combination of a therapeutically effective amount of a compound of Formula (I) optionally wherein the compound of formula (I) has the structure of 5 formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof and an antibody drug conjugate, wherein the compound and antibody drug conjugate are administered concurrently, sequentially or in admixture. In some embodiments, there is provided a compound of Formula (I) optionally wherein the 10 compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for use in treating cancer in a subject in need thereof in combination with an antibody drug conjugate, wherein the compound and antibody drug conjugate are administered concurrently, sequentially or in admixture. 15 In some embodiments, there is provided use of a compound of Formula (I) optionally wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof in the manufacture of a medicament for the treatment of cancer in a subject in need thereof in combination with an antibody drug conjugate, wherein the compound and 20 antibody drug conjugate are administered concurrently, sequentially or in admixture. In certain embodiments, the antibody drug conjugate is trastuzumab deruxtecan (T-DXd). In certain embodiments, the antibody drug conjugate is a TOPOisomerase antibody drug conjugate. In particular embodiments, the cancer is breast cancer, gastric cancer or non-small cell lung cancer (NSCLC). 25 In some embodiments, there is provided a method of treating cancer in a subject in need thereof comprising administering a combination of a therapeutically effective amount of a compound of Formula (I) optionally wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable 30 salt thereof, or a pharmaceutical composition thereof and a platinum-based anti-cancer drug, wherein the compound and platinum-based anti-cancer drug are administered concurrently, sequentially or in admixture. In some embodiments, there is provided a compound of Formula (I) optionally wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a 5 stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for use in treating cancer in a subject in need thereof in combination with a platinum-based anti-cancer drug, wherein the compound and platinum-based anti-cancer drug are administered concurrently, sequentially or in admixture. In some embodiments, there is provided use of a compound of Formula (I) optionally 10 wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof in the manufacture of a medicament for the treatment of cancer in a subject in need thereof in combination with a platinum-based anti-cancer drug, wherein the compound and platinum-based anti-cancer drug are administered concurrently, sequentially or in admixture. 15 In certain embodiments, the platinum-based anti-cancer drug is cisplatin, carboplatin, oxaliplatin, nedaplatin, lobaplatin, triplatin tetranitrate, triplatin tetranitrate, picoplatin, or satraplatin. In some embodiments, there is provided a method of treating cancer in a subject in need 20 thereof comprising administering a combination of a therapeutically effective amount of a compound of Formula (I) optionally wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof and a taxane, wherein the compound and taxane are administered concurrently, sequentially or in admixture. 25 In some embodiments, there is provided a compound of Formula (I) optionally wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for use in treating cancer in a subject in need thereof in combination with a taxane, wherein the compound and taxane are administered concurrently, sequentially or in admixture. 30 In some embodiments, there is provided use of a compound of Formula (I) optionally wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof in the manufacture of a medicament for the treatment of cancer in a subject in need thereof in combination with a taxane, wherein the compound and taxane are administered concurrently, sequentially or in admixture. 5 In certain embodiments, the taxane is docetaxel. In some embodiments, there is provided a method of treating cancer in a subject in need thereof comprising administering a combination of a therapeutically effective amount of a compound of Formula (I) optionally wherein the compound of formula (I) has the structure of 10 formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof in combination with immunotherapy, wherein the compound and immunotherapy are administered concurrently, sequentially or in admixture. In some embodiments, there is provided compound of Formula (I) optionally wherein the 15 compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for use in of treating cancer in a subject in need thereof in combination with immunotherapy, wherein the compound and immunotherapy are administered concurrently, sequentially or in admixture. 20 In some embodiments, there is provided use of compound of Formula (I) optionally wherein the compound of formula (I) has the structure of formula (I-A), a compound disclosed herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof in the manufacture of a medicament for the treatment of cancer in a subject in need thereof in combination with immunotherapy, wherein the compound and immunotherapy 25 are administered concurrently, sequentially or in admixture. In certain embodiments, the immunotherapy is an antibody, such as durvalumab. In particular embodiments, the immunotherapy is durvalumab and the cancer is non-small cell lung cancer (NSCLC). 30 Process Another aspect of the present specification provides a process for preparing a compound of the Formula (I), or a pharmaceutically acceptable salt thereof. A suitable process is illustrated by the following representative process variants in which, unless otherwise stated, G, Ga, Gb, Q1, Q2, Q3, R1, R2, Rz, X, Y, Za, Zb, Zc, and p have any of the meanings defined hereinbefore. Necessary starting materials may be obtained by standard procedures of organic chemistry. The preparation of such starting materials is described in conjunction with the following representative process variants and within the accompanying Examples. Alternatively, necessary starting materials are obtainable by analogous procedures to those illustrated which are within the ordinary skill of an organic chemist. Compounds of Formula (I) may 1. by reaction of another compound of formula (I) where Q1, Q2or Q3is C-OH with a primary or secondary alcohol under conditions known in the art as suitable for Mitsunobu reaction; or by reaction with a primary or secondary halide under typical conditions for nucleophilic substitution, e. g. a suitable solvent such as DMA or DMF in the presence of a suitable base, for example potassium carbonate or cesium carbonate at a suitable temperature (0-120 ºC) with or without a protecting group for other functionalities. 2. by reaction of another compound of formula (I) where Q1, Q2or Q3is C-LG, LG being a leaving group such as halogen, with a suitable amine under conditions known in the art, optionally catalysed by metal complexes such as palladium catalysts suitable for Buchwald- Hartwig amination reactions. 3. by reaction of another compound of formula (I) where Q1, Q2or Q3is C-LG, LG being a leaving group such as halogen, with a suitable alcohol under conditions known in the art (e. g. reaction in the presence of a strong base such sodium hydride to form the alkoxide), optionally catalysed by metal complexes such as palladium catalysts (e. g. RockPhos Pd G3) suitable for ether formation reactions. More generally, a compound of Formula (I) can be made from a compound of Formula (I) (e. g. via amide coupling, or reductive amination). 5 Compound of formula (I) where: Q1, Q2or Q3is C-OH, Q1, Q2or Q3is C-L-R, or where Q1, Q2or Q3is C-LG, and , of formula (II) with a compound of formula (III), 10 where LG is a leaving group known to the art, for example halide such as F, Cl or Br, or trifluoromethanesulfonate (triflate) (e.g. Examples 1, 2, 4 and 5). Conditions for the reaction may use a suitable solvent (for example DMA, DMF or NMP) in the presence of a suitable base (for example DIPEA) and a suitable temperature (such as from 0 ºC to ambient temperature, or at higher temperature such as 60-150 ^C), with or without a protecting group for other functionalities. 15 Alternative reaction conditions include the use of metal complex catalysts such as palladium catalysts in the presence of a base (for example cesium carbonate) in a suitable solvent (for example 1,4-dioxane) and a suitable temperature (such as ambient temperature to 90 ºC) (e.g. Example 3). 20 Compound of formula (II), for example where Q1, Q2or Q3is C-L-R, can be made by reaction of compound of formula (IV) with compound of formula (V) (e.g. Examples 1 and 4). Conditions for the reaction involved one step procedure and may use a suitable solvent (for example EtOH, isopropanol, dioxane, DMSO, or 2-methyltetrahydrofuran) and a suitable temperature (60-120 ºC), optionally in the presence of a mild oxidant (such as iron(III) chloride and / or atmospheric oxygen) and / or an acid (e. g. p-toluenesulfonic acid, acetic acid) and / or a 5 catalyst (e. g. copper(II) acetate). The reaction can be converted in a two-step procedure with the isolation of intermediate compound of formula (VI), where a mild oxidant (e. g. iron(III) chloride and / or oxygen) is added for the second step. Alternatively, compound of formula (II) can be made by reaction of compound of formula (IVa) with compound of formula (V). Conditions for the reaction may use a suitable solvent (for 10 example NMP and water) in the presence of a mild reducing agent such as sodium dithionate (also known as sodium hydrosulfite) at a suitable temperature (e. g.80-120 ºC). Compound of from compounds of formula (II) where Q1, Q2or Q3is C-LG (e.g. Example 5). Where C-L-R is C-O-R (e.g. C-L-R 15 is C-O-(CH2)2N(CH3)2 in Example 5), conditions for the reaction may use metal complex catalysts such as palladium catalysts in the presence of a base (for example potassium phosphate) in a suitable solvent (for example toluene) and a suitable temperature (such as ambient temperature to 90 ºC) (e.g. Example 3). 20 Compound of formula (II), for example where Q1, Q2or Q3is C-LG, can be made by reaction of compound of formula (IV) with compound of formula (Va) (e.g. Example 5). Conditions for the reaction may use a suitable solvent (e.g. sulfolane) in the presence of an oxidant (e.g. phosphoryl trichloride) and optionally in the presence of ammonium chloride, at a suitable temperature (e.g.80-120 ºC). 25

[0006] Compound of formula (IV) can be made by reaction of formulae (IVa) by reduction of the nitro group to the amino group (e. g. in the presence of iron with a suitable solvent such as ethanol) 5 (e.g. Example 3). When X= CH2, compound of made from reaction between compound of formula (VII) and compound of formula (VIIIa) under conditions known in the art as suitable for reductive amination. 10 Alternatively compound of formula (IVa) can be made from reaction between compound of formula (VIIa) and compound of formula (VIII). Conditions for the reaction may use an inert solvent (for example DMF) in the presence of a base (such as triethylamine or potassium carbonate) and a suitable temperature (e. g. room temperature or at higher temperature such as 60 ºC). 15 Alternatively compounds (II) can be obtained from reaction between compound of formula (IIa) and compound of formula (VIIIb) under conditions known in the art as suitable for nucleophilic substitution (e.g. Example 2) or from reaction between compound of formula (IIa) and compound of formula (VIIIc) under conditions known in the art as suitable for Mitsunobu 5 reactions. Compounds of formula (IIa) can be made by reaction of compound of formula (IVb) with 10 compound of formula (V) (e.g. Example 2). Conditions for the reaction may use a Lewis acid (for example ferric chloride) in a suitable solvent (for example MeOH) and a suitable temperature (60- 120 ºC). 15 Compounds of Formula ( ay be also made from reaction between compound of formula (XXI) and compound of formula (VIIIb) under conditions known in the art as suitable for nucleophilic substitution (e. g. Example 23). or from reaction between compound of formula (XXI) and compound of formula (VIIIc) 20 under conditions known in the art as suitable for Mitsunobu reactions.

[0007] It d of formula (I), may be made by reaction already illustrated above. 5 EXAMPLES General Experimental Conditions and Abbreviations The compounds described in this specification are further illustrated in the following Examples. The compounds were named using Chemdraw version 20.0.2.51. These Examples are given by way of illustration only and are non-limiting. In general: 10 Reagents and solvents (all anhydrous HPLC-grade) were obtained from commercial suppliers and used without any further purification unless otherwise stated. All reagents were weighed and handled in air unless otherwise stated. Brine refers to a saturated solution of NaCl. Concentration under reduced pressure refers to the use of a rotary evaporator. Operations were carried out at ambient temperature, i.e. in the range 17 to 25 °C and under 15 an atmosphere of an inert gas such as nitrogen unless otherwise stated. Evaporations were carried out by rotary evaporation under reduced pressure utilising a warm or hot water bath or utilising Genevac equipment or Biotage v10 evaporator in vacuo and work up procedures were carried out after removal of residual solids by filtration. Flash chromatographic purifications were performed on an automated Teledyne Isco 20 CombiFlash® Rf, Teledyne Isco CombiFlash® Companion® or CHEETAH® MP200 system with integrated UV detection using prepacked silica gel columns (40-60 μm) or C18 spherical (20-35 μm) using the chromatographic conditions as detailed in corresponding experimental data. Preparative reverse phase HPLC was performed on an Agilent 1290 Infinity II Preparative system equipped with a SQ MS detector (Multimode ESI / APCI source), with a Waters CSH C18 OBD column (5 microns silica, 30 mm diameter, 100 mm length); Waters MassLynx system with integrated MS detection, with a XBridge or Xselect CSH Prep C18 OBD column 5 (5µm silica, 30 mm diameter, 150 mm length); Gilson GX-281 with integrated UV detection, with either XBridge (10μm, 19mm diameter, 150 mm length) or Sunfire C18 columns (10μm, 19 mm diameter, 250 mm length) using decreasingly polar mixtures of water (containing 0.1—0.3% aqueous ammonium), water (containing 0.05% aqueous ammonia and 10 mmol NH4HCO3), water (containing 0.1% formic acid) or water (containing 0.05% TFA) and acetonitrile or methanol as 10 eluents. Preparative SFC purification was performed on either a Sepiatec P100 SFC system or Waters Prep 100 SFC system equipped with QDa MS detector, using the chromatographic conditions as detailed in corresponding experimental data. Preparative chiral HPLC was performed with a Gilson GX-281 system with integrated 15 UV detection and equipped with one of Chiralpak AS, AD, Chiralcel OD,OJ Chiralpak IA,IB,IC,ID,IE,IF,IG,IH columns (Daicel Chemical Industries, Ltd.) (R,R)-Whelk-O1, (S,S)- Whelk-O1 columns (Regis technologies, Inc. ) CHIRAL Cellulose-SB, SC, SA columns (YMC Co., Ltd.) at different column size (250x20mm, 250x30mm) with noted percentage of either ethanol in hexane (%Et / Hex) or isopropanol in hexane (%IPA / Hex) as isocratic solvent systems. 20 Yields, where present, are not necessarily the maximum attainable. In general, the structures of end-products of the Formula I were confirmed by nuclear magnetic resonance (NMR) spectroscopy;1H-NMR chemical shift values were measured on the delta scale and are quoted in ppm with measurement against TMS or residual solvent peaks as internal standards; proton magnetic resonance spectra were determined using a Bruker Avance 500 25 spectrometer at a proton frequency of 500 MHz, Bruker Avance 400, Bruker Avance III HD or Bruker Avance Neo spectrometers at a proton frequency of 400 MHz or Bruker Avance III, Avance III HD or Avance III NEO spectrometers at a proton frequency of 300 MHz ; measurements were taken at ambient temperature unless otherwise specified; the following abbreviations have been used: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; dd, doublet of doublets; ddd, doublet 30 of doublet of doublet; dt, doublet of triplets; br s, broad signal; hept, heptet. In general, end products of the Formula I were also characterized by mass spectrometry following liquid chromatography (LCMS or UPLC); reverse-phase C18 silica was used with a flow rate of 1 mL / min and detection was by Electrospray Mass Spectrometry and by UV / vis absorbance recording a wavelength range of 220-320 nm. Analytical UPLC was performed using a Waters Acquity UPLC CSH C18 column with dimensions 2.1 x 50 mm and particle size 1.7 micron). Gradient analysis was employed using decreasingly polar mixtures as eluent, for example decreasingly polar mixtures of water (containing 0.1% v / v formic acid or 0.3% ammonia v / v) as solvent A and acetonitrile as solvent B. A typical 1.7 minute analytical UPLC method would employ a solvent gradient over 1.3 min, at 1 mL / min, from a 97:3 mixture of solvents A and B respectively to a 3:97 mixture of solvents A and B. Also, LCMS was performed using a Shimadzu LCMS-2020 with electrospray ionization in positive ion detection mode with 20ADXR pump, SIL-20ACXR autosampler, CTO-20AC column oven, M20A PDA Detector and LCMS 2020 MS detector. LC was run in two set ups: 1) Halo C18 column (2.0 µm 3.0 x 30 mm) in combination with a gradient (5-100% B in 1.2 minutes) of water and formic acid - FA (0.1%) (A) and CH3CN and FA (0.1%) (B) at a flow rate of 1.5 mL / min; 2) Poroshell HPH C18 column (2.7 µm 3.0 x 50 mm) in combination with a gradient (5-95% B in 2 minutes) of aqueous 46 mM ammonium carbonate / ammonia buffer at pH 10 (A) and MeCN (B) at a flow rate of 1.2 mL / min ; 3) Halo C18 column (2.0 µm 3.0x30 mm) in combination with a gradient (5-95% B in 2 minutes) of water and TFA (0.05%) (A) and CH3CN and TFA (0.05%) at a flow rate of 1.5 mL / min (B).The Column Oven (CTO-20AC) temperature was 40.0℃.The injection volume was 1 µL. PDA (SPD-M20A) detection was in the range 190–400 nm. The MS detector, which was configured with electrospray ionization as ionizable source; Acquisition mode: Scan; Nebulizing Gas Flow:1.5 L / min; Drying Gas Flow:15 L / min; Detector Voltage: Tuning Voltage ± 0.2 kV; DL Temperature: 250 oC; Heat Block Temperature: 250 oC; Scan Range: 90.00 - 900.00 m / z. It is understood that, unless otherwise specified, the reported molecular ion corresponds to the [M+H]+, rounded to the lower unit. Typically, unless otherwise specified; for molecules with multiple isotopic patterns (e.g.35Cl,79Br,12C) only the lower most common isotope is reported. Ion exchange purification was generally performed using a SCX-2 (Biotage, Propylsulfonic acid functionalized silica. Manufactured using a trifunctional silane. Non end- capped) cartridge. Intermediate purity was assessed by thin layer chromatographic, mass spectral, HPLC (high performance liquid chromatography) and / or NMR analysis. The following abbreviations have been used: aq. Aqueous 5 DCM dichloromethane DIPEA / DIEA diisopropylethylamine DMA N,N-dimethylacetamide DMF N,N-dimethylformamide DMSO dimethyl sulfoxide 10 EtOAc ethyl acetate EtOH ethanol HPLC high performance liquid chromatography MeCN acetonitrile MeOH methanol 15 MeOD deuterated methanol MTBE tert-butyl methyl ether NMP N-Methyl-2-pyrrolidone rt / RT room temperature TFA trifluoroacetic acid 20 THF tetrahydrofuran Example 1 9-Benzyl-N-(tert-butyl)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9H-purin-6-amine

[0008] To tert-butyl 4-(2-(4-(9-benzyl-6-(tert-butylamino)-9H-purin-8-yl)-3- chlorophenoxy)ethyl)piperazine-1-carboxylate (150 mg, 0.24 mmol) was added TFA (3 mL) at RT. The resulting mixture was stirred for 30 minutes. The reaction mixture was then neutralised with aq. saturated NaHCO3. The reaction mixture was diluted with DCM (100 mL), and washed sequentially with saturated brine (15 mL x 3). The organic layer was dried over Na2SO4, filtered and evaporated to afford the crude product, which was purified by preparative HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5 μm) using decreasingly polar mixtures of water (containing 0.1% aq. NH3 and 10 mmol / L NH4HCO3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 9-benzyl- N-(tert-butyl)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9H-purin-6-amine (35 mg, 28 %) as a white solid.1H NMR (500 MHz, DMSO-d6): 1.52 (9H, s), 2.37–2.44 (4H, m), 2.69 (4H, s), 3.50 (2H, s), 4.17 (2H, t), 5.19 (2H, s), 6.86–6.92 (2H, m), 6.95 (1H, s), 6.97–7.05 (1H, m), 7.16– 7.23 (3H, m), 7.23–7.27 (1H, m), 7.34 (1H, d), 8.30 (1H, s). One proton not observed. m / z: ES+ [M+H]+ 520. Tert-butyl 4-(2-(4-(9-benzyl-6-(tert-butylamino)-9H-purin-8-yl)-3- chlorophenoxy)ethyl)piperazine-1-carboxylate used as starting material was made as follows: N4-benzyl-6-chloropyrimidine-4,5-diamine A mixture of phenylmethanamine (47.0 g, 439 mmol) and triethylamine (74.0 g, 732 mmol) was added dropwise to 4,6-dichloropyrimidin-5-amine (60.0 g, 366 mmol) in DMA (400 mL) at 100°C over a period of 20 minutes under air. The resulting solution was stirred at 100 °C for 8 hours. The resulting solution was poured into water (1000 mL) under stirring. The resulting precipitate was collected by filtration, washed with water (500 mL) and dried at 60 °C to afford N4-benzyl-6-chloropyrimidine-4,5-diamine (60.0 g, 70 %) as a pale yellow solid.1H NMR (300 MHz, DMSO-d6): 4.65 (2H, d), 5.11 (2H, s), 7.19–7.29 (1H, m), 7.29–7.45 (5H, m), 7.76 (1H, s). m / z: ES+ [M+H]+ 235. Tert-butyl 4-(2-(3-chloro-4-formylphenoxy)ethyl)piperazine-1-carboxylate (40 g, 255 mmol) was added to tert-butyl 4-(2- chloroethyl)piperazine-1-carboxylate (76 g, 307 mmol) and K2CO3 (70.6 g, 511 mmol) in MeCN (800 mL) at 25°C. The resulting mixture was stirred at 80 °C for 16 hours. The same reaction was repeated three more times and the combined four reaction mixtures were poured into water (2 L), extracted with EtOAc (3 x 1 L). The organic layer was dried over Na2SO4, filtered and evaporated to afford the crude product. The crude product was purified by crystallisation from EtOAc / heptane (1:1, 500 mL) to afford tert-butyl 4-(2-(3-chloro-4-formylphenoxy)ethyl)piperazine-1-carboxylate (131 g, 46 %) as a pale yellow solid.1H NMR (300 MHz, DMSO-d6): 1.38 (9H, s), 2.43 (4H, d), 2.73 (2H, d), 3.29 (4H, d), 4.17-4.27 (2H, m), 7.05-7.12 (1H, m), 7.21 (1H, d), 7.81 (1H, d), 10.18 (1H, d). m / z: ES+ [M+H]+ 369. Tert-butyl 4-(2-(4-(9-benzyl-6-chloro-9H-purin-8-yl)-3-chlorophenoxy)ethyl)piperazine-1- carboxylate

[0009] . g, dded to N4-benzyl-6-chloropyrimidine-4,5-diamine (60 g, 256 mmol) and tert-butyl 4-(2-(3-chloro-4-formylphenoxy)ethyl)piperazine-1-carboxylate (104 g, 281 mmol) in EtOH (1000 mL). The reaction was stirred at 60 °C for 2 days. The reaction mixture 5 was evaporated to dryness, redissolved in EtOAc (100 mL) and washed sequentially with water (100 mL x 3). The organic layer was dried over Na2SO4, filtered and evaporated to afford the crude product. The crude product was purified by flash C18-flash chromatography, elution gradient 40 to 70% MeCN in water. Pure fractions were evaporated to dryness to afford tert-butyl 4-(2-(4-(9- benzyl-6-chloro-9H-purin-8-yl)-3-chlorophenoxy)ethyl)piperazine-1-carboxylate (60.0 g, 40 %)10 as a yellow solid.1H NMR (300 MHz, DMSO-d6): 1.40 (9H, s), 2.45 (4H, t), 2.74 (2H, t), 3.3– 3.36 (4H, m), 4.22 (2H, t), 5.38 (2H, s), 6.85–7 (2H, m), 7.09 (1H, dd), 7.16–7.24 (3H, m), 7.29 (1H, d), 7.51 (1H, d), 8.86 (1H, s). m / z: ES+ [M+H]+ 583. Tert-butyl 4-(2-(4-(9-benzyl-6-(tert-butylamino)-9H-purin-8-yl)-3- 15 chlorophenoxy)ethyl)piperazine-1-carboxylate To tert-butyl 4-(2-(4-(9-benzyl-6-chloro-9H-purin-8-yl)-3- chlorophenoxy)ethyl)piperazine-1-carboxylate (200 mg, 0.34 mmol) was added tert-butylamine (6 mL, 57.1 mmol) at RT. The resulting mixture was stirred at 110 °C for 2 hours. The reaction mixture was diluted with EtOAc (150 mL), and washed sequentially with saturated brine (25 mL x 3). The organic layer was dried over Na2SO4, filtered and evaporated to afford the crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in petroleum ether. Pure fractions were evaporated to dryness to afford tert-butyl 4-(2-(4-(9- benzyl-6-(tert-butylamino)-9H-purin-8-yl)-3-chlorophenoxy)ethyl)piperazine-1-carboxylate (180 mg, 85 %) as a brown solid.1H NMR (300 MHz, DMSO-d6): 1.40 (9H, s), 1.52 (9H, s), 2.37– 2.47 (4H, m), 2.69–2.77 (2H, m), 3.31–3.34 (4H, m), 4.16–4.21 (2H, m), 5.19 (2H, s), 6.86–6.95 (3H, m), 6.98–7.05 (1H, m), 7.16–7.23 (3H, m), 7.30–7.39 (1H, m), 8.29 (1H, s). One proton not observed. m / z: ES+ [M+H]+ 620. Example 2 N-(tert-butyl)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine TFA (1 mL) was added slowly to tert-butyl 4-(2-(4-(6-(tert-butylamino)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-8-yl)-3-chlorophenoxy)ethyl)piperazine-1-carboxylate (450 mg, 0.71 mmol) in DCM (4 mL) at room temperature. The mixture was stirred for 10 minutes. The reaction mixture was diluted with DCM (50 mL), and washed sequentially with saturated brine (75 mL x 2), and water (75 mL). The organic layer was dried over Na2SO4, filtered and evaporated to afford the crude product. The crude product was purified by preparative HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5 μm) using decreasingly polar mixtures of water (containing 0.1% aq. NH3 and 10 mmol / L NH4HCO3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford N-(tert-butyl)-8-(2-chloro- 4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-9H-purin-6-amine (172 mg, 45%) as a white solid.1H NMR (400 MHz, DMSO-d6): 1.53 (9H, s), 2.19 (3H, s), 2.31–2.48 (4H, m), 2.62-2.70 (6H, m), 4.13 (2H, t), 5.24 (2H, s), 6.80 (1H, s), 6.92–6.96 (2H, m), 7.02-7.05 (1H, m), 7.19 (1H, d), 7.33 (1H, d), 8.19 (1H, d), 8.25 (1H, s). One proton not observed. m / z: ES+ [M+H]+ 535. Tert-butyl 4-(2-(4-(6-(tert-butylamino)-9-((4-methylpyridin-2-yl)methyl)-9H-purin-8-yl)- 3-chlorophenoxy)ethyl)piperazine-1-carboxylate used as starting material was made as follows: Tert-butyl 4-(2-(3-chloro-4-(6-chloro-9H-purin-8-yl)phenoxy)ethyl)piperazine-1- carboxylate was added to tert-butyl 4-(2-(3-chloro-4- formylphenoxy)ethyl)piperazine-1-carboxylate (23 g, 62.3 mmol) and 6-chloropyrimidine-4,5- diamine (8.19 g, 56.7 mmol) in MeOH (460 mL) at 25°C. The resulting mixture was stirred at 80 °C for 9 hours. The reaction was repeated two more times. The combined reaction mixtures were diluted with DCM (5 L) and neutralised with aq. saturated NaHCO3. The mixture was filtered through celite, extracted with DCM (3 x 1 L). The organic layer was dried over Na2SO4, filtered and evaporated to afford the crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% THF in DCM. Pure fractions were evaporated to dryness to afford tert-butyl 4-(2-(3-chloro-4-(6-chloro-9H-purin-8-yl)phenoxy)ethyl)piperazine- 1-carboxylate (21.3 g, 23 %) as a pale yellow solid.1H NMR (300 MHz, DMSO-d6): 1.40 (9H, s), 2.43-2.49 (4H, m), 2.72-2.80 (2H, m), 3.33 (4H, d), 4.19-4.27 (2H, m), 7.12-7.22 (1H, m), 7.31 (1H, d), 7.82 (1H, d), 8.76 (1H, s), 14.06 (1H, s). m / z: ES+ [M+H]+ 493. Tert-butyl 4-(2-(3-chloro-4-(6-chloro-9-((4-methylpyridin-2-yl)methyl)-9H-purin-8- 5 yl)phenoxy)ethyl)piperazine-1-carboxylate 12.2 mmol) was added to tert-butyl 4-(2-(3-chloro-4-(6- chloro-9H-purin-8-yl)phenoxy)ethyl)piperazine-1-carboxylate (2.00 g, 4.05 mmol) and 2- (chloromethyl)-4-methylpyridine (0.861 g, 6.08 mmol) in MeCN (20 mL) at RT. The resulting 10 mixture was stirred at 80 °C for 2 hours. The reaction was repeated and the two reaction mixtures were combined, diluted with EtOAc (100 mL), washed sequentially with saturated brine (100 mL x 2) and water (100 mL). The organic layer was dried over Na2SO4, filtered and evaporated to afford the crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in petroleum ether. Pure fractions were evaporated to dryness to afford15 tert-butyl 4-(2-(3-chloro-4-(6-chloro-9-((4-methylpyridin-2-yl)methyl)-9H-purin-8- yl)phenoxy)ethyl)piperazine-1-carboxylate (2.00 g, 42 %) as a yellow solid.1H NMR (300 MHz, DMSO-d6): 1.40 (9H, s), 2.20 (3H, s), 2.44 (4H, t), 2.73 (2H, t),3.27-3.33 (3H, m), 4.18 (3H, t), 5.44 (2H, s), 6.94 (1H, s), 6.99–7.06 (2H, m), 7.25 (1H, d), 7.46 (1H, d), 8.17 (1H, d), 8.81 (1H, s). m / z: ES+ [M+H]+ 598. 20 Tert-butyl 4-(2-(4-(6-(tert-butylamino)-9-((4-methylpyridin-2-yl)methyl)-9H-purin-8-yl)-3- chlorophenoxy)ethyl)piperazine-1-carboxylate

[0010] , . added slowly to tert-butyl 4-(2-(3-chloro-4-(6-chloro-9- ((4-methylpyridin-2-yl)methyl)-9H-purin-8-yl)phenoxy)ethyl)piperazine-1-carboxylate (500 mg, 0.84 mmol) and tert-butylamine (611 mg, 8.35 mmol) in DMA (5 mL) at 0°C. The resulting 5 mixture was stirred at 25 °C for 2 hours. The reaction mixture was evaporated to dryness and redissolved in DCM (20 mL), and washed sequentially with water (15 mL x 3) and saturated brine (15 mL x 3). The organic layer was dried over Na2SO4, filtered and evaporated to afford crude product, which was used in the next step without further purification. m / z: ES+ [M+H]+ 635. 10 Example 3 N-(tert-butyl)-2-(2-chloro-4-(2-(dimethylamino)ethoxy)phenyl)-1-((4-methylpyridin-2- yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine (1-ethylpropyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-15 2-ylidene]dichloro(2-methylpyridine) (29.5 mg, 0.04 mmol) was added to 2-(3-chloro-4-(4- chloro-1-((4-methylpyridin-2-yl)methyl)-1H-imidazo[4,5-c]pyridin-2-yl)phenoxy)-N,N- dimethylethan-1-amine (160 mg, 0.35 mmol), tert-butylamine (30.8 mg, 0.42 mmol) and Cs2CO3 (228 mg, 0.70 mmol) in 1,4-dioxane (1 mL) at RT over a period of 5 minutes under nitrogen. The resulting mixture was stirred at 90 °C for 5 days. The solvent was removed under reduced pressure. The crude product was purified by preparative HPLC (XBridge Prep OBD C18 Column, 30*150 mm, 5 μm), using decreasingly polar mixtures of water (containing 0.1% aq. NH3 and 10 mmol / L NH4HCO3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford N-(tert-butyl)-2-(2-chloro-4-(2-(dimethylamino)ethoxy)phenyl)-1-((4- methylpyridin-2-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine (30.2 mg, 17 %) as a white solid. 1H NMR (400 MHz, DMSO-d6): 1.51 (9H, s), 2.13–2.28 (9H, m), 2.63 (2H, t), 4.13 (2H, t), 5.23 (2H, s), 5.71 (1H, s), 6.69 (1H, d), 6.80 (1H, s), 6.99 (1H, dd), 7.07 (1H, d), 7.21 (1H, d), 7.40 (1H, d), 7.74 (1H, d), 8.25 (1H, d). m / z: ES+ [M+H]+ 493. 2-(3-Chloro-4-(4-chloro-1-((4-methylpyridin-2-yl)methyl)-1H-imidazo[4,5-c]pyridin-2- yl)phenoxy)-N,N-dimethylethan-1-amine used as starting material was made as follows: 4-(2-Bromoethoxy)-2-chlorobenzaldehyde (96 g, 511 mmol) was added to 2-chloro-4-hydroxybenzaldehyde (8.0 g, 51.1 mmol) and K2CO3(17.6 g, 128 mmol) in MeCN (160 mL) at RT under nitrogen. The resulting mixture was stirred at 60 °C for 8 hours. The reaction mixture was filtered through celite, diluted with EtOAc (500 mL) and washed with saturated brine (150 mL x 3). The organic layer was dried over Na2SO4, filtered and evaporated to afford the crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in petroleum ether. Pure fractions were evaporated to dryness to afford 4-(2-bromoethoxy)-2-chlorobenzaldehyde (9.40 g, 70 %) as a pale yellow solid.1H NMR (300 MHz, DMSO-d6): 3.79–3.89 (2H, m), 4.44–4.54 (2H, m), 7.07–7.17 (1H, m), 7.23 (1H, d), 7.84 (1H, d), 10.20 (1H, d). m / z: ES+ [M+H]+ 264 {37Cl, 79Br or35Cl,81Br isotopes}. 2-Chloro-4-(2-(dimethylamino)ethoxy)benzaldehyde e (10.27 g, 227.7 mmol) was added slowly to 4-(2-bromoethoxy)-2- chlorobenzaldehyde (6.0 g, 22.77 mmol) in MeOH (120 mL) under nitrogen. The resulting mixture was stirred at 60 °C for 2 hours. The reaction mixture was diluted with EtOAc (200 mL) and washed sequentially with saturated brine (50 mL x 3). The organic layer was dried over Na2SO4, filtered and evaporated to afford the crude product. The crude product was purified by flash silica chromatography, elution gradient 40% to 100% EtOAc in petroleum ether. Pure fractions were evaporated to dryness to afford 2-chloro-4-(2-(dimethylamino)ethoxy)benzaldehyde (4.50 g, 87 %) as a yellow solid.1H NMR (300 MHz, DMSO-d6): 2.84 (6H, s), 3.49–3.58 (2H, m), 4.44–4.56 (2H, m), 7.12–7.21 (1H, m), 7.28 (1H, d), 7.87 (1H, d), 10.21 (1H, d). m / z: ES+ [M+H]+ 228. 2-Chloro-N-((4-methylpyridin-2-yl)methyl)-3-nitropyridin-4-amine (17.19 g, 124.36 mmol) was added to 2,4-dichloro-3-nitropyridine (8.0 g, 41.4 mmol) and (4-methylpyridin-2-yl)methanamine dihydrochloride (6.47 g, 33.16 mmol) in MeCN (160 mL) at RT. The resulting mixture was stirred at 60 °C for 2 hours. The reaction mixture was filtered through celite, diluted with EtOAc (500 mL) and washed sequentially with saturated brine (75 mL x 3). The organic layer was dried over Na2SO4, filtered and evaporated to afford the crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 60% EtOAc in petroleum ether. Pure fractions were evaporated to dryness to afford 2-chloro-N-((4- methylpyridin-2-yl)methyl)-3-nitropyridin-4-amine (5.30 g, 46 %) as a yellow solid.1H NMR (400 MHz, DMSO-d6): 2.31 (3H, s), 4.55 (2H, d), 6.84 (1H, d), 7.11–7.18 (2H, m), 7.99 (1H, d), 8.09 (1H, t), 8.40 (1H, d). m / z: ES+ [M+H]+ 279. 2-Chloro-N4-((4-methylpyridin-2-yl)methyl)pyridine-3,4-diamine (5.01 g, 89.70 mmol) was added to 2-chloro-N-((4-methylpyridin-2-yl)methyl)-3- 5 nitropyridin-4-amine (5.0 g, 17.9 mmol) and ammonium chloride (4.80 g, 89.7 mmol) in EtOH (100 mL) and water (10 mL). The resulting mixture was stirred at 80 °C for 16 hours. The reaction mixture was filtered through celite. The reaction mixture was diluted with EtOAc (300 mL) and washed sequentially with saturated brine (50 mL x 3). The organic layer was dried over Na2SO4, filtered and evaporated to afford the crude product. The crude product was purified by flash silica 10 chromatography, elution gradient 0 to 20% MeOH in DCM. Pure fractions were evaporated to dryness to afford 2-chloro-N4-((4-methylpyridin-2-yl)methyl)pyridine-3,4-diamine (3.00 g, 67 %) as a brown solid.1H NMR (400 MHz, DMSO-d6): 2.28 (3H, s), 4.43 (2H, d), 4.85 (2H, s), 6.30 (1H, d), 6.53 (1H, t), 7.10 (1H, dd), 7.17 (1H, s), 7.35 (1H, d), 8.39 (1H, d). m / z: ES+ [M+H]+ 249. 15 2-(3-Chloro-4-(4-chloro-1-((4-methylpyridin-2-yl)methyl)-1H-imidazo[4,5-c]pyridin-2- yl)phenoxy)-N,N-dimethylethan-1-amine 8.04 mmol) was added to 2-chloro-N4-((4-methylpyridin-2-20 yl)methyl)pyridine-3,4-diamine (2.00 g, 8.04 mmol) and 2-chloro-4-(2- (dimethylamino)ethoxy)benzaldehyde (2.20 g, 9.65 mmol) in EtOH (40 mL) under air. The resulting mixture was stirred at 80 °C for 16 hours. The solvent was removed under reduced pressure. Manganese(IV) oxide (0.699 g, 8.04 mmol) was added to the mixture in DCM (40 mL) at RT over a period of 5 minutes under air. The resulting solution was stirred at RT for 4 hours. The reaction mixture was filtered through celite, diluted with EtOAc (200 mL) and washed sequentially with water (50 mL x 2) and saturated brine (50 mL x 2). The organic layer was dried over Na2SO4, filtered and evaporated to afford the crude product. The crude product was purified by flash silica chromatography, elution gradient 50 to 100% EtOAc in petroleum ether. Pure fractions were evaporated to dryness to afford 2-(3-chloro-4-(4-chloro-1-((4-methylpyridin-2- yl)methyl)-1H-imidazo[4,5-c]pyridin-2-yl)phenoxy)-N,N-dimethylethan-1-amine (1.50 g, 41 %) as a brown solid.1H NMR (300 MHz, DMSO-d6): 2.22 (3H, s), 2.68 (6H, s), 3.29 (2H, t), 4.38 (2H, t), 5.43 (2H, s), 6.92 (1H, s), 7.05–7.13 (2H, m), 7.31 (1H, d), 7.52 (1H, d), 7.69 (1H, d), 8.18 (1H, d), 8.22 (1H, d). m / z: ES+ [M+H]+ 458 {37Cl,35Cl isotopes}. Example 4 4-(4-(6-(Tert-butylamino)-9-(3-chlorobenzyl)-9H-purin-8-yl)-3-chlorophenoxy)-2- methylbutanoic acid (racemic) 9-(3-chlorobenzyl)-9H-purin-8-yl)phenoxy)-2- methylbutanoate (racemic, 160 mg, 0.31 mmol) was added to tert-butylamine (158 mg, 2.15 mmol) and DIPEA (796 mg, 6.16 mmol) in DMF (5 mL). The resulting mixture was stirred at 60 °C for 6 hours. The reaction mixture was concentrated and then diluted with EtOAc (5 mL), and washed sequentially with water (15 mL x 2). The organic layer was dried over Na2SO4, filtered and evaporated to afford crude methyl 4-(4-(6-(tert-butylamino)-9-(3-chlorobenzyl)-9H-purin-8-yl)-3- chlorophenoxy)-2-methylbutanoate (racemic), which was added to sodium hydroxide (185 mg, 4.62 mmol) in THF:H2O (5:1, 5 mL). The resulting mixture was stirred at 60 °C for 6 hours. The reaction mixture was acidified with 2M HCl and then purified by preparative HPLC (Column: Xbridge Prep C18 OBD, 30*150 mm, 5 μm), using decreasingly polar mixtures of water (containing 0.1% aq. NH3 and 10 mmol / L NH4HCO3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 4-(4-(6-(tert-butylamino)-9-(3- chlorobenzyl)-9H-purin-8-yl)-3-chlorophenoxy)-2-methylbutanoic acid (racemic, 40.0 mg, 24%) as a white solid.1H NMR (500 MHz, DMSO-d6): 1.16 (3H, d), 1.53 (9H, s), 1.76–1.85 (1H, m), 2.03–2.11 (1H, m), 2.54–2.6 (1H, m), 4.10 (2H, t), 5.19 (2H, s), 6.83–6.96 (2H, m), 6.98–7.04 (2H, m), 7.2–7.29 (3H, m), 7.37 (1H, d), 8.31 (1H, d), 12.24 (1H, s). m / z: ES+ [M+H]+ 542. Methyl-4-(3-chloro-4-(6-chloro-9-(3-chlorobenzyl)-9H-purin-8-yl)phenoxy)-2- methylbutanoate (racemic) used as starting material was made as follows: Methyl-4-iodo-2-methylbutanoate (racemic) iodide (132 g, 883 mmol) was added to methyl-4-chloro-2-methylbutanoate (racemic, 19.0 g, 126 mmol) in acetone (380 mL) at RT. The resulting mixture was stirred at 70 °C for 24 hours. The reaction mixture was diluted with EtOAc (1 L) and filtered through celite. The organic layer was dried over Na2SO4, filtered and evaporated to afford the crude product. (21.0 g, 69%) as a yellow gum.1H NMR (300 MHz, DMSO-d6): 1.08 (3H, d), 1.77–1.89 (1H, m), 2.08–2.15 (1H, m), 2.48–2.56 (1H, m), 3.23 (2H, t), 3.60 (3H, s). m / z: ES+ [M+H]+ 243. Methyl-4-(3-chloro-4-formylphenoxy)-2-methylbutanoate (racemic) (26.5 g, 192 mmol) was added to 2-chloro-4-hydroxybenzaldehyde (10 g, 63.9 mmol) and methyl-4-iodo-2-methylbutanoate (racemic, 15.46 g, 63.87 mmol) in MeCN (300 mL). The resulting mixture was stirred at 80 °C for 10 hours. The solvent was removed under reduced pressure. The reaction mixture was concentrated and diluted with EtOAc (200 mL), and washed sequentially with water (400 mL x 2). The organic layer was dried over Na2SO4, filtered and evaporated to dryness to afford methyl-4-(3-chloro-4-formylphenoxy)-2-methylbutanoate (racemic, 16.0 g, 93 %) as a yellow oil.1H NMR (300 MHz, MeOD): 1.24 (3H, d), 1.77–2.01 (2H, m), 2.1–2.26 (1H, m), 3.70 (3H, s), 4.15 (2H, t), 6.97–7.03 (1H, m), 7.06 (1H, d), 7.87 (1H, d), 10.28 (1H, d). m / z: ES+ [M+H]+ 271. 6-Chloro-N4-(3-chlorobenzyl)pyrimidine-4,5-diamine methanamine (30 g, 211.9 mmol) was added to 4,6-dichloropyrimidin-5- amine (31.3 g, 190.7 mmol) and DIPEA (82 g, 635.6 mmol) in butan-1-ol (1000 mL). The resulting mixture was stirred at 120 °C for 24 hours. The solvent was removed under reduced pressure. The reaction mixture was concentrated and diluted with EtOAc (500 mL), and washed sequentially with water (1L x 2). The organic layer was dried over Na2SO4, filtered and evaporated to afford 6- chloro-N4-(3-chlorobenzyl)pyrimidine-4,5-diamine (45.0 g, 79 %) as a yellow solid.1H NMR (300 MHz, DMSO-d6): 4.63 (2H, d), 5.10 (2H, s), 6.21 (1H, s), 7.30 (1H, d), 7.32 (1H, t), 7.34 (1H, s), 7.36 (1H, s), 7.74 (1H, s). m / z: ES+ [M+H]+ 269. Methyl-4-(3-chloro-4-(6-chloro-9-(3-chlorobenzyl)-9H-purin-8-yl)phenoxy)-2- methylbutanoate (racemic) FeCl3 (12.05 g, 74.31 mmol) was added to 6-chloro-N4-(3-chlorobenzyl)pyrimidine-4,5- diamine (8.0 g, 29.73 mmol) and methyl-4-(3-chloro-4-formylphenoxy)-2-methylbutanoate (racemic, 6.04 g, 22.29 mmol) in 2-methyltetrahydrofuran (300 mL) at 25°C under air. The resulting mixture was stirred at 70 °C for 10 hours. The reaction mixture was concentrated and diluted with EtOAc (200 mL), and washed sequentially with water (400 mL x 2). The organic layer was dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 60% EtOAc in petroleum ether. Pure fractions were evaporated to dryness to afford rac-methyl 4-(3-chloro-4-(6-chloro-9-(3- chlorobenzyl)-9H-purin-8-yl)phenoxy)-2-methylbutanoate (5.00 g, 39 %) as a yellow solid.1H NMR (400 MHz, DMSO-d6): 1.17 (3H, d), 1.81–1.94 (1H, m), 2.03–2.15 (1H, m), 2.64–2.75 (1H, m), 3.63 (3H, s), 4.13 (2H, t), 5.38 (2H, s), 6.89 (1H, d), 6.99 (1H, d), 7.06 (1H, dd), 7.2–7.33 (3H, m), 7.51 (1H, d), 8.87 (1H, s). m / z: ES+ [M+H]+ 521. {37Cl an two35Cl isotopes}. Example 5 N-(tert-butyl)-8-(2-chloro-4-(2-(dimethylamino)ethoxy)phenyl)-N-methyl-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine -N-(tert-butyl)-N-methyl-9-((4-methylpyridin-2-yl)methyl)- 9H-purin-6-amine (163 mg, 0.33 mmol), bis[cinnamyl palladium(II) chloride] (6.6 mg, 0.02 mmol), di-tert-butyl(2',4',6'-triisopropyl-[1,1'-biphenyl]-2-yl)phosphane (13.6 mg, 0.03 mmol) and potassium phosphate (106 mg, 0.50 mmol) was added to a microwave vial and degassed at RT. A degassed mixture of 2-(dimethylamino)ethan-1-ol (0.148 mL, 1.47 mmol) in toluene (1.5 mL) was added and placed in the microwave for 16 hours at 60 °C. The reaction mixture concentrated, filtered and dissolved in 4 mL DMSO, then purified by preparative HPLC (Waters CSH C18 OBD, 30 x 100 mm, 5 μm), using decreasingly polar mixtures of H2O (containing 0.1% aqueous formic acid) and MeCN as eluents. The compound was further purified by ion exchange chromatography using an SCX column. The desired product was eluted from the column using 7M NH3 / MeOH and pure fractions were evaporated to dryness. The sample was dissolved in 2 mL DMSO and then purified by preparative HPLC (Waters CSH C18 OBD, 30 x 100 mm, 5 μm), using decreasingly polar mixtures of H2O (containing 0.3% aqueous ammonium hydroxide) and MeCN as eluents to give N-(tert-butyl)-8-(2-chloro-4-(2-(dimethylamino)ethoxy)phenyl)-N- methyl-9-((4-methylpyridin-2-yl)methyl)-9H-purin-6-amine (14.7 mg, 8.9 %) as a solid.1H NMR (500 MHz, DMSO-d6): 1.60 (9H, s), 2.19 (3H, s), 2.21 (6H, s), 2.62 (2H, t), 3.68 (3H, s), 4.11 (2H, t), 5.27 (2H, s), 6.82 (1H, s), 6.94 (1H, dd), 7.03 (1H, d), 7.18 (1H, d), 7.37 (1H, d), 8.19 (1H, d), 8.25 (1H, s). m / z: ES+ [M+H]+ 508. 8-(4-Bromo-2-chlorophenyl)-N-(tert-butyl)-N-methyl-9-((4-methylpyridin-2-yl)methyl)- 9H-purin-6-amine used as starting material was made as follows: 6-Chloro-N4-((4-methylpyridin-2-yl)methyl)pyrimidine-4,5-diamine (250 mL) was added to 4,6-dichloropyrimidin-5-amine (6.72 g, 41.0 mmol) and (4-methylpyridin-2-yl)methanamine dihydrochloride (10 g, 51.7 mmol) followed by DIPEA (35.8 mL, 205 mmol). The reaction mixture was heated to 117 °C under nitrogen for 18 hrs. The reaction mixture was allowed to cool to RT, then diluted with EtOAc (800 mL), and washed with water and brine (800 mL each). The organic phase was evaporated to a brown solid, which was azeotroped with heptane. The crude material was triturated with MTBE to give 6-chloro-N4-((4- methylpyridin-2-yl)methyl)pyrimidine-4,5-diamine (9.10 g, 89 %) as a brown solid.1H NMR (500 MHz, CDCl3): 2.37 (3H, s), 3.63 (2H, d), 4.73 (2H, d), 6.43 (1H, s), 7.05 (1H, d), 7.13 (1H, s), 8.08 (1H, s), 8.40 (1H, d). m / z: ES+ [M+H]+ 250. 8-(4-bromo-2-chlorophenyl)-6-chloro-9-((4-methylpyridin-2-yl)methyl)-9H-purine ((4-methylpyridin-2-yl)methyl)pyrimidine-4,5-diamine (4.00 g, 16.0 mmol), 4-bromo-2-chlorobenzoic acid (3.39 g, 14.42 mmol) and ammonium chloride (5.14 g, 96.1 mmol) in sulfolane (100 mL) was added phosphoryl trichloride (7.47 mL, 80.1 mmol) at RT. The reaction mixture was heated to 120 °C and stirred. After 10 hours the mixture was allowed to cool to RT. The reaction mixture was poured into a 1:1 stirred solution of MeCN / H2O (300 mL) and 5 M aqueous NaOH was added cautiously to the stirred solution until the pH was above 7. The reaction mixture was diluted with MTBE (300 mL) and the organic layer was separated. The aqueous layer was extracted with MTBE (200 mL x 3). The combined organics were dried over MgSO4 and concentrated. The crude residue was diluted with H2O (50 mL) and MTBE (50 mL) and the organic layer was separated and washed sequentially with H2O (50 mL) and brine (50 mL). The organics were dried over MgSO4and concentrated in vacuo. The crude product was purified by basic alumina chromatography, elution gradient 0-30% EtOAc in heptanes. The pure fractions were evaporated to afford 8-(4-bromo-2-chlorophenyl)-6-chloro-9-((4-methylpyridin-2- yl)methyl)-9H-purine (4.10 g, 57%) as a white solid.1H NMR (500 MHz, CDCl3): 2.25 (3H, s), 5.45 (2H, s), 6.79 (1H, s), 6.94 (1H, d), 7.28 (1H, s), 7.42 (1H, dd), 7.68 (1H, d), 8.20 (1H, d), 8.78 (1H, s). m / z: ES+ [M+H]+ 448. 8-(4-Bromo-2-chlorophenyl)-N-(tert-butyl)-N-methyl-9-((4-methylpyridin-2-yl)methyl)-9H- purin-6-amine

[0011] 8-(4-bromo-2-chlorophenyl)-6-chloro-9-((4-methylpyridin-2-yl)methyl)- 9H-purine (149.6 mg, 0.33 mmol) in NMP (1 mL) was added N,2-dimethylpropan-2-amine (291 mg, 3.34 mmol) and DIPEA (0.09 mL, 0.52 mmol). The mixture was stirred at 150 °C for 8 hours in the microwave. The crude product was purified by preparative HPLC (Waters XSelect CSH C18 ODB column, 5 µ silica, 30 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing by volume 1% aq. NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 8-(4-bromo-2-chlorophenyl)-N-(tert- butyl)-N-methyl-9-((4-methylpyridin-2-yl)methyl)-9H-purin-6-amine (163 mg, 98 %) as a colourless gum.1H NMR (500 MHz, CDCl3): 1.64 (9H, s), 2.22 (3H, s), 3.72 (3H, s), 5.36 (2H, s), 6.71 (1H, s), 6.90 (1H, d), 7.17 (1H, d), 7.36 (1H, dd), 7.63 (1H, d), 8.23 (1H, d), 8.39 (1H, s). m / z: ES+ [M+H]+ 499. Example 6 The following examples in Tables A, B and C were synthesised as stated in the Table or in the notes at the bottom of Tables A, B and C. Table A All compounds in Table A were made in a similar method to Example 1. LCMS Example Structure Name1H NMR [M+H] + (500 MHz, CDCl3): 0.79 – 0.83 (2H, m), 0.89 – 0.93 (2H, m), 1.57 (3H, s), 2.58 9-benzyl-8-(2- (4H, s), 2.82 (2H, t), chloro-4-(2- 2.95 (4H, t), 4.14 (piperazin-1- (2H, t), 5.27 (2H, s), A1 yl)ethoxy)phenyl)- 6.21 (1H, s), 6.81 518 N-(1- (1H, dd), 6.93 (2H, methylcyclopropyl) dd), 7.06 (1H, d), -9H-purin-6-amine 7.10 (1H, d), 7.13 – 7.19 (3H, m), 8.57 (1H, s). One exchangeable not observed. (400 MHz, DMSO- d6): 1.59 (3H, s), 1.76–1.88 (2H, m), 2.05–2.15 (2H, m), 9-benzyl-8-(2- 2.35–2.49 (6H, m), chloro-4-(2- 2.63–2.73 (6H, m), (piperazin-1- 4.17 (2H, t), 5.20 A2 yl)ethoxy)phenyl)- (2H, s), 6.88–6.94 (2H, m), 6.99 532 N-(1- –7.04 methylcyclobutyl)- (1H, m), 7.17–7.22 9H-purin-6-amine (3H, m), 7.24 (1H, d), 7.36 (1H, d), 7.87 (1H, s), 8.26 (1H, s). One exchangeable proton was not seen. Table B All compounds in Table B were made in a similar method to Example 4. 1 LCMS Example Structure Name H NMR [M+H] + (400 MHz, DMSO- d6): 1.14 (3H, d), 1.64 (6H, s), 1.76– 1.83 (1H, m), 1.87– 4-(3-chloro-4-(9- 1.95 (4H, m), 2.02– (3-chlorobenzyl)-6- 2.11 (1H, m), 2.56 (2,2- (1H, d), 4.10 (2H, t), B1 dimethylpyrrolidin- 4.17 (2H, s), 5.21 1-yl)-9H-purin-8- (2H, s), 6.83 (1H, d), 568 yl)phenoxy)-2- 6.93 (1H, d), 7.01 methylbutanoic (1H, dd), 7.19–7.27 acid (racemic) (3H, m), 7.35 (1H, d), 8.27 (1H, s).One exchangeable proton not seen. (400 MHz, DMSO- d6): 1.15 (3H, d), 4-(3-chloro-4-(9- 1.68 (1H, s), 1.80 (3-chlorobenzyl)-6- (2H, dq), 2.07 (3H, (1- dd), 2.55 (3H, d), azaspiro[3.3]heptan 3.24 (2H, d), 4.11 B2 -1-yl)-9H-purin-8- (3H, t), 4.39 (1H, s), 566 yl)phenoxy)-2- 5.24 (2H, s), 6.82 methylbutanoic (1H, d), 6.91 (1H, s), acid (racemic) 7.03 (1H, d), 7.18– 7.33 (4H, m), 8.31 (1H, s), 12.19 (1H, s). (400 MHz, DMSO- d6): 1.15 (3H, d), 1.60 (3H, s), 1.73– 4-(3-chloro-4-(9- 1.89 (3H, m), 2.01– (3-chlorobenzyl)-6- 2.15 (3H, m), 2.38– ((1- 2.48 (2H, m), 2.56 B3 methylcyclobutyl)a (1H, d), 4.10 (2H, t), mino)-9H-purin-8- 5.19 (2H, s), 6.85 554 yl)phenoxy)-2- (1H, d), 6.94 (1H, s), methylbutanoic 7–7.06 (1H, m), acid (racemic) 7.19–7.29 (3H, m), 7.38 (1H, d), 7.92 (1H, s), 8.27 (1H, s), 11.39 (1H, s). (500 MHz, DMSO- d6, 24°C): 1.15 (3H, d), 1.74–1.84 (1H, m), 2.02–2.11 (1H, 4-(4-(6- m), 2.18 (6H, s), 2.48 (bicyclo[1.1.1]pent (1H, s), 2.57 (1H, d), an-1-ylamino)-9- 4.09 (2H, t), 5.21 B4 (3-chlorobenzyl)- (2H, s), 6.83 (1H, d), 9H-purin-8-yl)-3- 6.91 (1H, s), 7.02 552 chlorophenoxy)-2- (1H, dd), 7.19–7.29 methylbutanoic (3H, m), 7.38 (1H, acid (racemic) d), 8.32 (1H, s), 8.58 (1H, s). One exchangeable proton not seen. (500 MHz, DMSO- d6, 24°C): 1.14 (3H, d), 1.60 (9H, s), 1.73–1.82 (1H, m), 4-(4-(6-(tert- 2–2.1 (1H, m), 2.54 butyl(methyl)amin (1H, s), 3.66 (3H, s), o)-9-(3- 4.10 (2H, t), 5.22 B5 chlorobenzyl)-9H- (2H, s), 6.8–6.85 purin-8-yl)-3- (1H, m), 6.94 (1H, 556 chlorophenoxy)-2- d), 7.02 (1H, dd), methylbutanoic 7.18–7.29 (3H, m), acid (racemic) 7.38 (1H, d), 8.31 (1H, s). One exchangeable proton not seen. (400 MHz, DMSO- d6, 20°C): 1.13 (3H, 4-(3-chloro-4-(9- d), 1.74–1.85 (6H, (3-chlorobenzyl)-6- m), 1.89–1.96 (1H, (5- m), 2–2.08 (1H, m), azas 2.14 (2H, t), 2.52– B6 piro[3.4]octan- 5-yl)-9H-purin-8- 2.56 (1H, m), 3.58 580 yl)phenoxy)-2- (2H, d), 4.09 (4H, t), methylbutanoic 5.23 (2H, s), 6.82 acid (racemic) (1H, d), 6.92 (1H, d), 7.01 (1H, dd), 7.18– 7.28 (3H, m), 7.35 (1H, d), 8.35 (1H, s). One exchangeable proton not seen. (400 MHz, DMSO- d6, 20°C): 1.13 (3H, d), 1.72–1.85 (1H, m), 2.01–2.11 (1H, 4-(3-chloro-4-(9- m), 2.52–2.59 (1H, (3-chlorobenzyl)-6- m), 2.74 (2H, t), (6-oxa-1- 4.06–4.35 (4H, m), azaspiro[3.3]h 4.57 (2H, s), 5.24 B7 eptan -1-yl)-9H-purin-8- (2H, s), 5.54 (2H, d), 568 yl)phenoxy)-2- 6.82 (1H, dd), 6.91 methylbutanoic (1H, d), 7.02 (1H, acid (racemic) dd), 7.19–7.3 (3H, m), 7.36 (1H, s), 8.38 (1H, s). One exchangeable proton not seen. (500 MHz, DMSO- d6): 1.13 (3H, d), 1.73–1.89 (3H, m), 2.01–2.1 (1H, m), 4-(3-chloro-4-(9- 2.39 (2H, t), 2.53 (3-chlorobenzyl)-6- (1H, d), 4.06–4.15 (2-oxa-5- (4H, m), 4.30 (2H, B8 azaspiro[3.4]octan- d), 5.25 (2H, s), 5.77 5-yl)-9H-purin-8- (2H, d), 6.83 (1H, d), 582 yl)phenoxy)-2- 6.93 (1H, d), 7.02 methylbutanoic (1H, dd), 7.19–7.29 acid (racemic) (3H, m), 7.35 (1H, d), 8.43 (1H, s). One exchangeable proton not seen. 4-(3-chloro-4-(9- (500 MHz, DMSO- (3-chlorobenzyl)-6- d6, 23°C): 0.63–0.7 ((1- (2H, m), 0.80 (2H, t), methylcyclopropyl) 1.15 (3H, d), 1.46 B9 amino)-9H-purin- (3H, s), 1.74–1.84 y)-2- (1H, m), 2.02 540 8-yl)phenox –2.12 methylbutanoic (1H, m), 2.53–2.58 acid (racemic) (1H, m), 4.10 (2H, t), 5.20 (2H, s), 6.84 (1H, d), 6.93 (1H, d), 7.01 (1H, dd), 7.18– 7.3 (3H, m), 7.38 (1H, d), 8.23 (1H, s), 8.35 (1H, s), 12.24 (1H, s). (500 MHz, DMSO- d6, 24°C): 1.14 (3H, d), 1.69 (6H, d), 1.75–1.84 (1H, m), 4-(3-chloro-4-(9- 2.01–2.09 (1H, m), (3-chlorobenzyl)-6- 2.19–2.25 (2H, m), (2,2- 2.55 (1H, t), 4.01– B10 dimethylazetidin-1- 4.13 (3H, m), 4.42 yl)-9H-purin-8- (1H, t), 5.21 (2H, d), 554 yl)phenoxy)-2- 6.82 (1H, d), 6.91 methylbutanoic (1H, d), 6.99–7.05 acid (racemic) (1H, m), 7.18–7.29 (3H, m), 7.38 (1H, dd), 8.25 (1H, d). One exchangeable proton not seen. (400 MHz, MeOD): 0.57–0.63 (2H, m), 1.24 (3H, d), 1.84– 1.93 (1H, m), 2.03 (2H, t), 2.06–2.12 4-(3-chloro-4-(9- (2H, m), 2.13–2.22 (3-chlorobenzyl)-6- (1H, m), 2.39–2.49 (4- (2H, m), 2.57–2.68 B11 azaspiro[2.4]heptan (1H, m), 4.07–4.19 -4-yl)-9H-purin-8- (2H, m), 4.33 (2H, t), 566 yl)phenoxy)-2- 5.26 (2H, s), 6.78– methylbutanoic 6.86 (2H, m), 6.95 acid (racemic) (1H, dd), 7.15 (1H, d), 7.17–7.24 (3H, m), 8.17 (1H, s). One exchangeable proton not seen. Table C The following examples in Table C were synthesised using similar methods previously exemplified in Examples described above. POLQ POLQ PD Enz Prolif x# Structure Name ES F Lumin Lumin E ormula (MH+) Primar BRCA y CR) 2 - / - GMean mean pIC50 pIC50 C1 8-(2-chloro-4-(2- 561 C30 H37 6.7 5.1 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N- cyclohexyl-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C2 8-(2-chloro-4-(2- 569 C28 H31 6.9 <5.0 (piperazin-1- Cl F2 N8 yl)ethoxy)phenyl)-N-(3,3- O difluorocyclobutyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C3 (R)-2-((8-(2-chloro-4-(2- 563 C29 H35 5.4 <5.0 (piperazin-1- Cl N8 O2 yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- yl)amino)-2- cyclopropylethan-1-ol C4 N-(bicyclo[1.1.1]pentan-1- 545 C29 H33 8.2 6.3 yl)-8-(2-chloro-4-(2- Cl N8 O (piperazin-1- yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C5 (R)-8-(2-chloro-4-(2- 573 C31 H37 6.3 5.4 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-6-(2- cyclopropylpyrrolidin-1- yl)-9-((4-methylpyridin-2- yl)methyl)-9H-purine C6 (R)-8-(2-chloro-4-(2- 547 C29 H35 7.2 5.6 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N-(1- cyclopropylethyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C7 8-(2-chloro-4-(2- 561 C30 H37 6.9 5.8 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N- (cyclopentylmethyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C8 8-(2-chloro-4-(2- 547 C29 H35 7.3 5.5 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N-((1- methylcyclopropyl)methyl )-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6- amine C9 8-(2-chloro-4-(2- 563 C30 H39 6.9 5.8 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N-(2- ethylbutyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C10 8-(2-chloro-4-(2- 547 C29 H35 5.8 <5.0 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-6-(3,3- dimethylazetidin-1-yl)-9- ((4-methylpyridin-2- yl)methyl)-9H-purine C11 8-(2-chloro-4-(2- 563 C30 H39 5.6 5.6 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N-(3,3- dimethylbutyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C12 (S)-8-(2-chloro-4-(2- 549 C28 H33 6.0 <5.0 (piperazin-1- Cl N8 O2 yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-N- (tetrahydrofuran-3-yl)-9H- purin-6-amine C13 8-(2-chloro-4-(2- 565 C29 H34 6.7 <5.0 (piperazin-1- Cl F N8 yl)ethoxy)phenyl)-N-((1- O fluorocyclobutyl)methyl)- 9-((4-methylpyridin-2- yl)methyl)-9H-purin-6- amine C14 8-(2-chloro-4-(2- 563 C29 H35 5.2 <5.0 (piperazin-1- Cl N8 O2 yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-N- ((tetrahydrofuran-2- yl)methyl)-9H-purin-6- amine (racemic) C15 8-(2-chloro-4-(2- 535 C28 H35 5.9 5.5 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N,N- diethyl-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C16 8-(2-chloro-4-(2- 563 C29 H35 5.3 <5.0 (piperazin-1- Cl N8 O2 yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-N-(tetrahydro- 2H-pyran-4-yl)-9H-purin- 6-amine C17 8-(2-chloro-4-(2- 533 C28 H33 6.7 5.3 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N- (cyclopropylmethyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C18 (1-((8-(2-chloro-4-(2- 577 C30 H37 7.1 5.3 (piperazin-1- Cl N8 O2 yl)ethoxy)phenyl)-9-((4- methylpyridin-2-yl)methyl)- 9H-purin-6- yl)amino)cyclopentyl)methan ol C19 8-(2-chloro-4-(2- 547 C29 H35 6.0 5.5 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N- cyclobutyl-N-methyl-9- ((4-methylpyridin-2- yl)methyl)-9H-purin-6- amine C20 8-(2-chloro-4-(2- 547 C29 H35 5.8 <5.0 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N- cyclopropyl-N-ethyl-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C21 (S)-3-((8-(2-chloro-4-(2- 565 C29 H37 5.2 5.1 (piperazin-1- Cl N8 O2 yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- yl)amino)-2-methylbutan- 2-ol C22 (1-((8-(2-chloro-4-(2- 549 C28 H33 6.3 <5.0 (piperazin-1- Cl N8 O2 yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- yl)amino)cyclopropyl)met hanol C23 8-(2-chloro-4-(2- 553 C28 H34 6.5 <5.0 (piperazin-1- Cl F N8 yl)ethoxy)phenyl)-N-(2- O fluoro-2-methylpropyl)-9- ((4-methylpyridin-2- yl)methyl)-9H-purin-6- amine C24 8-(2-chloro-4-(2- 547 C29 H35 8.3 6.3 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N-(1- methylcyclobutyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C25 8-(2-chloro-4-(2- 561 C30 H37 5.7 <5.0 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-6-(3,3- dimethylpyrrolidin-1-yl)- 9-((4-methylpyridin-2- yl)methyl)-9H-purine C26 8-(2-chloro-4-(2- 565 C29 H34 6.6 5.4 (piperazin-1- Cl F N8 yl)ethoxy)phenyl)-N-((1- O (fluoromethyl)cyclopropyl )methyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C27 (S)-8-(2-chloro-4-(2- 563 C30 H39 6.8 5.7 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N-(3,3- dimethylbutan-2-yl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C28 (1S,3R)-3-((8-(2-chloro-4- 563 C29 H35 5.1 <5.0 (2-(piperazin-1- Cl N8 O2 yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- yl)amino)cyclopentan-1-ol C29 8-(2-chloro-4-(2- 561 C30 H37 8.1 6.4 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-6-(2,2- dimethylpyrrolidin-1-yl)- 9-((4-methylpyridin-2- yl)methyl)-9H-purine C30 8-(2-chloro-4-(2- 547 C29 H35 5.8 <5.0 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N- (cyclopropylmethyl)-N- methyl-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C31 8-(2-chloro-4-(2- 547 C29 H35 7.2 5.6 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N- (cyclobutylmethyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C32 8-(2-chloro-4-(2- 561 C30 H37 7.0 5.4 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N-((1- methylcyclobutyl)methyl)- 9-((4-methylpyridin-2- yl)methyl)-9H-purin-6- amine C33 8-(2-chloro-4-(2- 533 C28 H33 7.1 5.1 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N- cyclobutyl-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C34 (S)-8-(2-chloro-4-(2- 547 C29 H35 6.9 5.4 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-6-(2- methylpyrrolidin-1-yl)- 9H-purine C35 8-(2-chloro-4-(2- 559 C30 H35 5.4 5.3 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-6-(5- azaspiro[2.4]heptan-5-yl)- 9H-purine C36 8-(2-chloro-4-(2- 561 C30 H37 5.4 5.5 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N- (cyclobutylmethyl)-N- methyl-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C37 8-(2-chloro-4-(2- 547 C29 H35 6.3 5.1 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N-(2- cyclopropylethyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C38 8-(2-chloro-4-(2-(piperazin- 547 C29 H35 7.4 5.3 1-yl)ethoxy)phenyl)-N- Cl N8 O cyclopentyl-9-((4- methylpyridin-2-yl)methyl)- 9H-purin-6-amine C39 8-(2-chloro-4-(2- 561 C30 H37 6.5 5.7 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N-(2- cyclobutylethyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C40 1-((8-(2-chloro-4-(2- 551 C28 H35 5.4 <5.0 (piperazin-1- Cl N8 O2 yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- yl)amino)-2- methylpropan-2-ol C41 8-(2-chloro-4-(2- 557 C27 H31 7.4 5.2 (piperazin-1- Cl F2 N8 yl)ethoxy)phenyl)-N-(2,2- O difluoropropyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C42 8-(2-chloro-4-(2- 563 C29 H35 5.3 <5.0 (piperazin-1- Cl N8 O2 yl)ethoxy)phenyl)-N- ((1s,3s)-3- methoxycyclobutyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine C43 (3-((8-(2-chloro-4-(2- 563 C29 H35 5.3 <5.0 (piperazin-1- Cl N8 O2 yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- yl)amino)cyclobutyl)meth anol (unknown stereochemistry) C44 (R)-2-((8-(2-chloro-4-(2- 551 C28 H35 5.4 <5.0 (piperazin-1- Cl N8 O2 yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- yl)amino)butan-1-ol C45 (R)-8-(2-chloro-4-(2- 549 C28 H33 6.1 <5.0 (piperazin-1- Cl N8 O2 yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-N- (tetrahydrofuran-3-yl)-9H- purin-6-amine C46 (R)-8-(2-chloro-4-(2- 547 C29 H35 6.2 5.1 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-6-(2- methylpyrrolidin-1-yl)- 9H-purine C47 (S)-8-(2-chloro-4-(2- 573 C31 H37 5.8 5.5 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-6-(2- cyclopropylpyrrolidin-1- yl)-9-((4-methylpyridin-2- yl)methyl)-9H-purine C48 8-(2-chloro-4-(2- 563 C29 H35 5.7 <5.0 (piperazin-1- Cl N8 O2 yl)ethoxy)phenyl)-N-((1- methoxycyclopropyl)meth yl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6- amine C49 8-(2-chloro-4-(2- 551 C28 H32 6.8 <5.0 (piperazin-1- Cl F N8 yl)ethoxy)phenyl)-N-(3- O fluorocyclobutyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine (unknown stereochemistry) C50 (S)-8-(2-chloro-4-(2- 563 C29 H35 5.5 <5.0 (piperazin-1- Cl N8 O2 yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-N-(tetrahydro- 2H-pyran-3-yl)-9H-purin- 6-amine C51 8-(2-chloro-4-(2- 565 C29 H37 7.9 5.8 (piperazin-1- Cl N8 O2 yl)ethoxy)phenyl)-N-(1- methoxy-2-methylpropan- 2-yl)-9-((4-methylpyridin- 2-yl)methyl)-9H-purin-6- amine C52 8-(2-chloro-4-(2- 547 C29 H35 7.8 5.6 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N-(1- cyclopropylethyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- amine (racemic) C53 8-(2-chloro-4-(2- 533 C28 H33 5.6 <5.0 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-6-(3- methylazetidin-1-yl)-9-((4- methylpyridin-2- yl)methyl)-9H-purine (racemic) C54 8-(2-chloro-4-(2- 533 C28 H33 6.2 5.1 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-N- cyclopropyl-N-methyl-9- ((4-methylpyridin-2- yl)methyl)-9H-purin-6- amine C55 8-(2-chloro-4-(2-(piperazin- 563 C30 H39 6.9 5.5 1-yl)ethoxy)phenyl)-N-(3,3- Cl N8 O dimethylbutan-2-yl)-9-((4- methylpyridin-2-yl)methyl)- 9H-purin-6-amine (racemic) C56 8-(2-chloro-4-(2- 576 C28 H30 5.8 <5.0 (piperazin-1- Cl N9 O yl)ethoxy)phenyl)-9-((4- S methylpyridin-2- yl)methyl)-N-(thiazol-5- ylmethyl)-9H-purin-6- amine C57 8-(2-chloro-4-(2- 576 C28 H30 5.3 <5.0 (piperazin-1- Cl N9 O yl)ethoxy)phenyl)-9-((4- S methylpyridin-2- yl)methyl)-N-(thiazol-2- ylmethyl)-9H-purin-6- amine C58 (R)-8-(2-chloro-4-(2- 583 C32 H35 7.0 5.4 (piperazin-1- Cl N8 O yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-N-(1- phenylethyl)-9H-purin-6- amine C59 2-((8-(2-chloro-4-(2- 564 C28 H34 <4.0 <5.0 (piperazin-1- Cl N9 O2 yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- yl)amino)-N,N- dimethylacetamide C60 N-(2-((8-(2-chloro-4-(2- 564 C28 H34 <4.0 <5.0 (piperazin-1- Cl N9 O2 yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purin-6- yl)amino)ethyl)acetamide C61 6-(7- 559 C30 H35 6.5 5.5 azabicyclo[2.2.1]heptan-7- Cl N8 O yl)-8-(2-chloro-4-(2- (piperazin-1- yl)ethoxy)phenyl)-9-((4- methylpyridin-2- yl)methyl)-9H-purine C62 3-((8-(2-chloro-4-(2- 583 C27 H31 5.7 <5.0 (piperazin-1- Cl N8 O3 yl)ethoxy)phenyl)-9-((4- S methylpyridin-2- yl)methyl)-9H-purin-6- yl)amino)thietane 1,1- dioxide Example 7 Table D: Assay Results for Examples 1-5 and A1-A2, B1-B11 POLQ Enz POLQ PD Lumin Primary Prolif POLQ PD Prolif Example # CR) Lumin Lumin DLD1 GMean BRCA2 - / - mean pIC50 mean pIC50 pIC50 1 8.2 7.1 5.8 2 8.3 7.0 5.1 3 8.3 7.2 4 8.1 6.6 <5.0 5 8.0 6.5 A1 8.6 6.2 5.3 A2 7.0 5.9 <5.0 B1 7.8 5.4 <5.0 B2 6.8 5.1 <5.0 B3 8.1 6.2 <5.0 B4 8.1 5.8 <5.0 B5 7.9 5.5 B6 7.1 <5.0 B7 6.4 <5.0 B8 6.5 <5.0 B9 8.2 6.0 B10 7.7 5.2 B11 7.5 <5.0 Polθ polymerase domain enzyme inhibition The following assay was used to identify compounds that inhibit Polθ polymerase domain. 5 The ability of compounds to inhibit the isolated polymerase domain (I1780-V2590) of DNA polymerase theta (Polθ) was assessed in a PPiLight inorganic pyrophosphate assay (Lonza, product code LT07-610) with the luminescent end point detection of the formation of the product inorganic pyrophosphate (PPi). The PPiLight inorganic pyrophosphate assay provides a high-throughput screening method to monitoring polymerase activity by quantifying the amount of PPi released 10 during the polymerisation reaction using luciferase. DNA template In the assay, Polθ interacts with the substrates (deoxy thymidine triphosphate (dTTP) (Sigma, product code T0251) and a DNA template with a 17-nucleotide overhang (Eurogentec, custom creates order), and PPi is formed due to the polymerase reaction. This free PPi interacts 15 with AMP, to generate the ATP used in the luciferase reaction in the production of light. The test compound competitive binding inhibits the polymerase reaction, resulting in the loss of luminescence. The assay was performed as follows with all reagent additions carried out using a CERTUS FLEX liquid dispenser workstation: 20 Test compound (15 nL) was acoustically dispensed into Greiner 1536 well white small volume medium bind assay plates. 1X assay screening buffer (50 mM Tris pH7.5, 5 mM MgCl2, 0.01% v / v Pluronic F127, 2 mM DTT, 0.05 mg / ml BSA) is prepared. dTTP / DNA (1.5 µL) was dispensed of into each of the wells followed by 1.5 µL of Polθ, 25 the plates are covered and the reaction is allowed to progress for 20 minutes at room temperature. To quench, TFA (0.5 µL) was dispensed into the wells, then 2.0 µL of PPiLight reagent was dispensed into each well and incubated at room temperature for 1 hour. Plates were then read on an EnVision plate reader for luminescence 400-700 nm. Compounds were dosed directly from a compound source plate containing serially diluted compounds (4 wells containing 10 mM, 0. 1 mM, 1 µM and 10 nM respectively) to an assay microplate using a labcyte ECHO 550 liquid handler. The ECHO 550 using acoustic technology 5 to transfer between microplates of DMSO compound solutions, with the system being able to be programmed to transfer small nL volumes of compounds from different source plate wells to give serial dilutions for the compounds to be tested and backfilled to normalise the DMSO concentration across the dilution range. In total 15 nL of compound plus DMSO were added to each wells and compounds tested 10 over 12 concentrations points. The final concentration range was 10, 3.33333, 1.66667, 0.3, 0. 1, 0.025, 0.009, 0.003, 0.0015, 0.00027, 0.0001125 and 0.0000225 mM. The luminescence response measured on the EnVision for each compound was exported into Genedata to perform curve fitting analysis and expressed as an IC50 value. This was determined by calculation of the compound required to give a 50% reduction in control compound binding to Polθ. 15 Results are shown in Tables C and D above. Example 9 Homologous Recombination Synthetic Lethal Inhibition of Proliferation. This assay identifies anti-proliferative effects of POLQ compounds in the homologous 20 recombination deficient colorectal cell line DLD-1 BRCA2- / - over 8-9 population doublings (7 days for DLD-1 and 12 days for DLD-1 BRCA2- / -). DLD1 BRCA2 wt are used as a control to detect cell toxic effects not specific to homologous recombination deficiency. DLD-1 BRCA2- / - and DLD-1 cells were kept in continuous culture in Assay Medium (RPMI 1640 phenol red free (Sigma R7509) containing 1% GlutaMAX (Gibco 35050) and 10% 25 Foetal Bovine Serum (Gibco 10270-106)). On the day of the assay cells in culture of ~80 -90% confluent were used. Cell monolayers were washed with 10 mL PBS, then removed and added 2 mL TrypLE Express (Gibco 12604). The cells with TrypLE Express were incubated for 5 minutes in cell culture incubator and then the detached cells resuspend in 15 mL Assay Medium. Cells were counted using a ViCell and the cell images were monitored for clumps of cells, ideally they should be single or ≤ 3 cell clusters. The cells were diluted to 3,000 cells / mL of DLD-1 BRCA2- / - and 1,500 cells / mL of DLD-1 in Assay Medium and 100 µL added per well of transparent bottomed, black, tissue culture-treated 96-well plates (CoStar, No.3904) Assay Ready Plates. The Assay Ready Plates contain a 10 point 10 µM to 0.51 nM dose range with three-fold dilutions in 5 DMSO with a final volume of 100 nL. The plates were incubated at 37°C with 5% CO2for 6 days. On day 6, 100 µL / well of Assay Medium was added to duplicate Assay Ready Plates.90 µL of culture medium was removed from the cell plates and replenished with the Assay Media and compounds from the duplicate Assay Ready Plates using the Bravo. The plates were further incubated at 37°C with 5% CO2. On day 7 the plates containing DLD-1 and Cell Titre Glo 3D 10 (Promega G9683) were equilibrated to room temperature, then 60 µL of Cell Titre Glo 3D was added per well and incubated on a shaking platform for 30 min. Plates were read on the Envision measuring luminescence for 1 second per well. On day 12 the plates containing DLD-1 BRCA2- / - cells and Cell Titre Glo 3D (Promega G9683) were equilibrated to room temperature, then 60 µL Cell Titre Glo 3D added per well and incubated on a shaking platform for 30 min. Plates were 15 read on the Envision measuring luminescence for 1 second per well. The data was exported into a suitable software package (such as Genedata) to perform curve fitting analysis. 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Claims

CLAIMS 1. A compound of formula (I):or a stereoisomer or pharmaceutically acceptable salt thereof; wherein, R1and R2are each, independently, H, halo, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3hydroxyalkyl, -CN, C2-C4 alkynyl, or C2-C6 alkoxyalkyl; Q1, Q2, and Q3are, independently N, C-L-R, or CRx, wherein one and only one of Q1, Q2, and Q3is C-L-R; L is -O-; -C(O)-; -O(CH2)qC(O)-; -C(O)NRy-; -O(CH2)qC(O)NRy-; -O(CH2)qNRy; -NRy-; - (CH2)q-; -(CH2)qNRy-; -(CH2)qO-; -(CH2)qC(O)-; -(CH2)qC(O)O-; or -O(CH2)q-; q is, independently, 1, 2, or 3 R is H, Ra, Rb, Rc, or Rd; Rais a 3-10 membered heterocycle optionally substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, -CN, -S(O)2OH, C1-C4alkylamino, C1-C5alkoxy, C2-C5 alkoxyalkyl, 4-6 membered heterocycle, C1-C7 alkyl, S(O)2C1-C3 alkyl and -C(O)- C3-C6 carbocycle, wherein the C1-C7 alkyl is optionally substituted with 1 to 4 substituentsindependently selected from amino, carboxy, halo, hydroxy, oxo, -CN, C2-C8 ester, and C1-C5 alkoxy; Rbis a C1-C7 alkyl, wherein one or two methylene groups from the C1-C7 alkyl are optionally independently replaced with NRe, O, S, S(O) or CW1W2wherein W1and W2together form a C3- C6carbocycle, and one or two single bonds in a C2-C7alkyl chain are optionally independently replaced with a double or triple bond(s), wherein the C1-C7 alkyl is optionally substituted with 1 to 4 substituents independently selected from: halo, oxo, hydroxy, carboxy, amino, -CN, C2-C4 alkynyl, C2-C6 carbamate, C1-C8amide, C1-C4sulfonyl, C1-C4sulfonamide, C1-C4alkylamino, C1-C5alkoxy, C3-C6carbocycle, and 3-10 membered heterocycle, wherein the C3-C6 carbocycle is optionally substituted with 1 to 4 substituents independently selected from hydroxy, halo, and carboxy; wherein the 3-10 membered heterocycle is optionally substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, - CN, -S(O)2OH, C1-C4alkylamino, C1-C5alkoxy, C2-C5alkoxyalkyl, 4-6 membered heterocycle, and C1-C7 alkyl, wherein the C1-C7 alkyl is optionally substituted with 1 to 4 substituents independently selected from amino, carboxy, halo, hydroxy, oxo, -CN, C2-C8 ester, and C1-C5 alkoxy; Rcis a C3-C6carbocycle optionally substituted with 1 to 4 substituents independently selected from hydroxy halo, carboxy, C1-C3 alkyl, and CN; Rdis C1-C4 sulfonyl or C1-C4 sulfonamide;Ryis H, C1-C3 alkyl, or C1-C3 haloalkyl; Rxis H, halo, hydroxy, -CN, -NH2, C1-C3alkoxy, C1-C3alkyl, or C1-C3haloalkyl; Reis H, halo, C1-C8 alkyl, or C1-C8 haloalkyl; X is a C1-C4 alkylene; Y is a phenyl or 5-6 membered heteroaryl, wherein the phenyl or 5-6 membered heteroaryl is optionally substituted with 1 to 3 substituents independently selected from halo, C1-C3 alkyl, C1- C3 alkoxy, -CN, C1-C3 haloalkyl, and cyclopropyl;G is N or CH; Gaand Gbare N, CH, or CR5wherein one, and only one, of Gaand Gbis N or CH and one, and only one, of Ga and Gb is CR5; ;Rzis H, C1-C3 alkyl, or Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4- 6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3alkyl, and: when Rzis H or C1-C3 alkyl: (i) Zaand Zbare, independently, H, C1-C5 alkyl, or halo, wherein the C1-C5 alkyl is optionally substituted with hydroxy, or Zaand Zbtogether form a saturated C3- C6carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3 alkoxy, and C1-C3 alkyl optionally substituted with hydroxy, or Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, C1-C3 alkyl, halo, hydroxy, C1-C3 alkoxy, C2-C5 alkoxyalkyl, C3-C6 carbocycle, 5-6 membered heteroaryl, or phenyl, wherein the C1-C3alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide, or (ii) Za, Zband Zctogether form a 5-membered bicyclic ring system containing a bridge of 1 carbon atom;when Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl: Zband Zcare, independently, H, C1-C3 alkyl, or C3-C6 carbocycle, or Zband Zctogether form a C3-C6carbocycle or a 4-6 membered heterocycle, or Zbtogether with Rzand Zaform a 7-membered heterobicyclic ring system containing a bridge of 2 carbon atoms, and Zcis H.

2. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 1, wherein, R1and R2are each, independently, H or halo; Q1and Q3are each, independently, CH; Q2is C-L-Rbwherein L is O; Rbis a C1-C7 alkyl, wherein one or two methylene groups from the C1-C7 alkyl is optionally independently replaced with NRe, and wherein the C1-C7 alkyl is optionally substituted with carboxy or 3-10 membered heterocycle, Reis C1-C8 alkyl; X is a C1-C4 alkylene; Y is a phenyl or 5-6 membered heteroaryl, wherein the phenyl or 5-6 membered heteroaryl is optionally substituted with 1 to 3 substituents independently selected from halo and C1-C3alkyl; G is N or CH; Gb is N; Gais CR5; ;p is 0, 1 or 2; Rzis H, C1-C3alkyl, or Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4- 6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, and: when Rzis H or C1-C3alkyl: (i) Zaand Zbare, independently, H, C1-C5 alkyl, or halo, wherein the C1-C5 alkyl is optionally substituted with hydroxy, or Zaand Zbtogether form a saturated C3- C6carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3alkoxy, and C1-C3alkyl optionally substituted with hydroxy, or Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, C1-C3 alkyl, halo, hydroxy, C1-C3 alkoxy, C2-C5 alkoxyalkyl, C3-C6 carbocycle, 5-6 membered heteroaryl, or phenyl, wherein the C1-C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide, or (ii) Za, Zband Zctogether form a 5-membered bicyclic ring system containing a bridge of 1 carbon atom; when Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl: Zband Zcare, independently, H, C1-C3alkyl, or C3-C6carbocycle, or Zband Zctogether form a C3-C6 carbocycle or a 4-6 membered heterocycle, or Zbtogether with Rzand Zaform a 7-membered heterobicyclic ring system containing a bridge of 2 carbon atoms, and Zcis H.

3. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 1 or claim 2, wherein R1or R2is halo and the other is H.

4. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 3, wherein R1is Cl and R2is H.

5. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in any one of the preceding claims, wherein L is O and wherein Rbis a C1-C7alkyl, wherein the C1-C7alkyl is substituted with a 3-10 membered N-heterocycle.

6. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 5, wherein the 3-10 membered N-heterocycle is piperazinyl.

7. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 4, wherein L is O and wherein Rbis a C1-C7alkyl, wherein one methylene group from the C1-C7 alkyl is replaced with -N(CH3)-.

8. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 4, wherein L is O and wherein Rbis a C1-C7alkyl, wherein the C1-C7 alkyl is substituted with carboxy.

9. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in any one of the preceding claims, wherein X is CH2.

10. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in any one of the preceding claims, wherein Y is phenyl, wherein the phenyl is optionally substituted with halo.

11. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 9, wherein Y is pyridinyl, wherein the pyridinyl is substituted with methyl.

12. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in any one of the preceding claims, wherein G is N.

13. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 11, wherein G is CH.

14. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in any one of the preceding claims, wherein Gb is N.

15. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in any one of the preceding claims, wherein Rzis H or C1-C3alkyl.

16. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 15, wherein: Zaand Zbare, independently, H, C1-C5alkyl, or halo, wherein the C1-C5alkyl is optionally substituted with hydroxy, or Zaand Zbtogether form a saturated C3-C6 carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3 alkoxy, and C1-C3 alkyl optionally substituted with hydroxy, or Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and Zcis H, C1-C3 alkyl, halo, hydroxy, C1-C3 alkoxy, C2-C5 alkoxyalkyl, C3-C6 carbocycle, 5-6 membered heteroaryl, or phenyl, wherein the C1-C3alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide.

17. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 16, wherein Zaand Zbare, independently, H, C1-C5 alkyl, or halo, and wherein Zcis hydroxy, C2-C5 alkoxyalkyl, or C1-C3 alkyl, wherein the C1-C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide.

18. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 17, wherein Zcis C1-C3 alkyl, wherein the C1-C3 alkyl is optionally substituted with 1 to 3 substituents independently selected from hydroxy, halo, oxo, C1-C4 alkylamino, and C1-C3 amide.

19. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 16, wherein Zaand Zbare, independently, H or C1-C5alkyl, wherein the C1-C5 alkyl is optionally substituted with hydroxy, and wherein Zcis C3-C6 carbocycle.

20. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable saltthereof, as claimed in claim 19, wherein Zaand Zbare, independently, H or C1-C3 alkyl, wherein the C1-C3alkyl is optionally substituted with hydroxy, and wherein Zcis C3carbocycle.

21. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 16, wherein Zaand Zbare, independently, H or C1-C5alkyl, and wherein Zcis 5-6 membered heteroaryl, or phenyl.

22. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 21, wherein Zaand Zbare, independently, H or CH3, and wherein Zcis thiazolyl or phenyl.

23. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 16, wherein Zaand Zbtogether form a saturated C3-C6 carbocycle optionally substituted with 1 to 3 substituents independently selected from halo, hydroxy, C1-C3 alkoxy, and C1-C3 alkyl optionally substituted with hydroxy, and wherein Zcis H, halo, C1-C3 alkoxy, or C1-C3 alkyl optionally substituted with hydroxy or halo.

24. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 16, wherein Zaand Zbtogether form a saturated 4-6 membered heterocycle optionally substituted with 1 to 3 substituents independently selected from oxo, and wherein Zcis H.

25. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 24, wherein the saturated 4-6 membered heterocycle contains O or S.

26. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 15, wherein Za, Zband Zctogether form a 5-membered bicyclic ring system containing a bridge of 1 carbon atom.

27. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 26, wherein the bicyclic ring .

28. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 14, wherein Rztogether with Zaforms a 4-6 membered N-heterocycle, wherein the 4-6 membered N-heterocycle is optionally substituted with 1 to 3 substituents independently selected from C1-C3 alkyl.

29. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 28, wherein Zband Zcare, independently, H, C1-C3 alkyl, or C3-C6 carbocycle.

30. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 28 or claim 29, wherein Rztogether with Zaforms a 4-5 membered N-heterocycle optionally substituted with 1 or 2 CH3, and Zband Zcare, independently, H, CH3, or C3 carbocycle.

31. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 28, wherein Zband Zctogether form a C3-C6 carbocycle or a 4-6 membered heterocycle.

32. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 31, wherein Rztogether with Zaforms a 4-5 membered N- heterocycle, and wherein Zband Zctogether form a C3-C4 carbocycle.

33. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 31, wherein Rztogether with Zaforms a 4-5 membered N- heterocycle, and wherein Zband Zctogether form a 4 membered O-heterocycle.

34. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 28, wherein Zbtogether with Rzand Zaform a 7-membered heterobicyclic ring system containing a bridge of 2 carbon atoms, and Zcis H.

35. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in claim 34, wherein the heterobicyclic ring .

36. The compound of formula (I), or a stereoisomer orthereof, as claimed in any of the preceding claims, wherein p is 0.

37. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 35, wherein p is 1.

38. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt 5 thereof, as claimed in any one of claims 1 to 35, wherein p is 2.

39. A compound of formula (I) as claimed in claim 1 or claim 2, selected from: 9-Benzyl-N-(tert-butyl)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9H-purin-6- amine; N-(tert-butyl)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; N-(tert-butyl)-2-(2-chloro-4-(2-(dimethylamino)ethoxy)phenyl)-1-((4-methylpyridin-2- yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine; 4-(4-(6-(Tert-butylamino)-9-(3-chlorobenzyl)-9H-purin-8-yl)-3-chlorophenoxy)-2- methylbutanoic acid; 9-benzyl-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(1-methylcyclopropyl)-9H- purin-6-amine; 9-benzyl-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(1-methylcyclobutyl)-9H- purin-6-amine; N-(tert-butyl)-8-(2-chloro-4-(2-(dimethylamino)ethoxy)phenyl)-N-methyl-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 4-(3-chloro-4-(9-(3-chlorobenzyl)-6-(2,2-dimethylpyrrolidin-1-yl)-9H-purin-8- yl)phenoxy)-2-methylbutanoic acid; 4-(3-chloro-4-(9-(3-chlorobenzyl)-6-(2,2-dimethylazetidin-1-yl)-9H-purin-8- yl)phenoxy)-2-methylbutanoic acid; 4-(3-chloro-4-(9-(3-chlorobenzyl)-6-(4-azaspiro[2.4]heptan-4-yl)-9H-purin-8- yl)phenoxy)-2-methylbutanoic acid;4-(3-chloro-4-(9-(3-chlorobenzyl)-6-(1-azaspiro[3.3]heptan-1-yl)-9H-purin-8- yl)phenoxy)-2-methylbutanoic acid; 4-(3-chloro-4-(9-(3-chlorobenzyl)-6-((1-methylcyclobutyl)amino)-9H-purin-8- yl)phenoxy)-2-methylbutanoic acid; 5 4-(4-(6-(bicyclo[1.1.1]pentan-1-ylamino)-9-(3-chlorobenzyl)-9H-purin-8-yl)-3- chlorophenoxy)-2-methylbutanoic acid; 4-(4-(6-(tert-butyl(methyl)amino)-9-(3-chlorobenzyl)-9H-purin-8-yl)-3-chlorophenoxy)- 2-methylbutanoic acid; 4-(3-chloro-4-(9-(3-chlorobenzyl)-6-(5-azaspiro[3.4]octan-5-yl)-9H-purin-8- yl)phenoxy)-2-methylbutanoic acid; 4-(3-chloro-4-(9-(3-chlorobenzyl)-6-(6-oxa-1-azaspiro[3.3]heptan-1-yl)-9H-purin-8- yl)phenoxy)-2-methylbutanoic acid; 4-(3-chloro-4-(9-(3-chlorobenzyl)-6-(2-oxa-5-azaspiro[3.4]octan-5-yl)-9H-purin-8- yl)phenoxy)-2-methylbutanoic acid; 4-(3-chloro-4-(9-(3-chlorobenzyl)-6-((1-methylcyclopropyl)amino)-9H-purin-8- yl)phenoxy)-2-methylbutanoic acid; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-cyclohexyl-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-6-(3,3-dimethylazetidin-1-yl)-9-((4- methylpyridin-2-yl)methyl)-9H-purine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(3,3-dimethylbutyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; (S)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-N- (tetrahydrofuran-3-yl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-((1-fluorocyclobutyl)methyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine;8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-N- ((tetrahydrofuran-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N,N-diethyl-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; 5 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-N- (tetrahydro-2H-pyran-4-yl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(cyclopropylmethyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; (1-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)- 9H-purin-6-yl)amino)cyclopentyl)methanol; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-cyclobutyl-N-methyl-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(3,3-difluorocyclobutyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-cyclopropyl-N-ethyl-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; (S)-3-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-yl)amino)-2-methylbutan-2-ol; (1-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)- 9H-purin-6-yl)amino)cyclopropyl)methanol; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(2-fluoro-2-methylpropyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(1-methylcyclobutyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-6-(3,3-dimethylpyrrolidin-1-yl)-9-((4- methylpyridin-2-yl)methyl)-9H-purine;8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-((1- (fluoromethyl)cyclopropyl)methyl)-9-((4-methylpyridin-2-yl)methyl)-9H-purin-6-amine; (S)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(3,3-dimethylbutan-2-yl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 5 (1S,3R)-3-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-yl)amino)cyclopentan-1-ol; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-6-(2,2-dimethylpyrrolidin-1-yl)-9-((4- methylpyridin-2-yl)methyl)-9H-purine; (R)-2-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-yl)amino)-2-cyclopropylethan-1-ol; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(cyclopropylmethyl)-N-methyl-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(cyclobutylmethyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-((1-methylcyclobutyl)methyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-cyclobutyl-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-6-(5- azaspiro[2.4]heptan-5-yl)-9H-purine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-6-(5- azaspiro[2.4]heptan-5-yl)-9H-purine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(cyclobutylmethyl)-N-methyl-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(2-cyclopropylethyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine;8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-cyclopentyl-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(2-cyclobutylethyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 5 N-(bicyclo[1.1.1]pentan-1-yl)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 1-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)- 9H-purin-6-yl)amino)-2-methylpropan-2-ol; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(2,2-difluoropropyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-((1s,3s)-3-methoxycyclobutyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; (3-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)- 9H-purin-6-yl)amino)cyclobutyl)methanol; (R)-2-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-yl)amino)butan-1-ol; (R)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)- N-(tetrahydrofuran-3-yl)-9H-purin-6-amine; (R)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-6- (2-methylpyrrolidin-1-yl)-9H-purine; (S)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-6-(2-cyclopropylpyrrolidin-1-yl)-9- ((4-methylpyridin-2-yl)methyl)-9H-purine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-((1-methoxycyclopropyl)methyl)-9- ((4-methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(3-fluorocyclobutyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine;(R)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-6-(2-cyclopropylpyrrolidin-1-yl)-9- ((4-methylpyridin-2-yl)methyl)-9H-purine; (S)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-N- (tetrahydro-2H-pyran-3-yl)-9H-purin-6-amine; 5 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(1-methoxy-2-methylpropan-2-yl)-9- ((4-methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(1-cyclopropylethyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-6-(3-methylazetidin-1-yl)-9-((4- methylpyridin-2-yl)methyl)-9H-purine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-cyclopropyl-N-methyl-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(3,3-dimethylbutan-2-yl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-N- (thiazol-5-ylmethyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)-N- (thiazol-2-ylmethyl)-9H-purin-6-amine; (R)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)- N-(1-phenylethyl)-9H-purin-6-amine; 2-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)- 9H-purin-6-yl)amino)-N,N-dimethylacetamide; (R)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(1-cyclopropylethyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; N-(2-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-yl)amino)ethyl)acetamide;6-(7-azabicyclo[2.2.1]heptan-7-yl)-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9- ((4-methylpyridin-2-yl)methyl)-9H-purine; 3-((8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-9-((4-methylpyridin-2-yl)methyl)- 9H-purin-6-yl)amino)thietane 1,1-dioxide; 5 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(cyclopentylmethyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-((1-methylcyclopropyl)methyl)-9-((4- methylpyridin-2-yl)methyl)-9H-purin-6-amine; 8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-N-(2-ethylbutyl)-9-((4-methylpyridin-2- yl)methyl)-9H-purin-6-amine; and pharmaceutically acceptable salts thereof.

40. A pharmaceutical composition which comprises a compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 39, and at least one pharmaceutically acceptable excipient.

41. A compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 39, or a pharmaceutical composition as claimed in claim 40, for use in the treatment cancer.

42. A method of treating cancer which comprises administering to a patient in need thereof, a therapeutically effective amount of a compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 39 or of a pharmaceutical composition as claimed in claim 40.

43. Use of a compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 39, or a pharmaceutical composition as claimed in claim 40, in the manufacture of a medicament for the treatment of cancer in a subject.

44. The compound of formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, or pharmaceutical composition for use as claimed in claim 41, the method as claimed in claim 42 or the use as claimed in claim 43, wherein the cancer is breast, ovarian,pancreatic, or prostate cancer.

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