DNA POLYMERASE THETA INHIBITORS

Abstract

The present invention relates to compounds of the Formula I, and pharmaceutically salts thereof, wherein ring A, R1, R2, R3, integer a, integer b, X4, X5, X6 and X7 are each as defined herein. The compounds of the present invention inhibit Polθ. The novel therapeutic compounds are therefore useful for the treatment and / or prevention of diseases and conditions in which Polθ activity is implicated, such as, for example but not limited to, the treatment and / or prevention of cancer. The present invention also relates to pharmaceutical compositions comprising the novel therapeutic compounds defined herein, to processes for synthesising these compounds and to their use for the treatment of diseases and / or conditions in which Polθ activity is implicated.

Description

DNA POLYMERASE THETA INHIBITORS INTRODUCTION

[001] The present invention relates to new therapeutic compounds. More specifically, the present invention relates to novel therapeutic compounds that inhibit PiOI. The novel therapeutic compounds are therefore useful for the treatment and / or prevention of diseases and conditions in which PiOI activity is involved, such as, for example, but not limited to, the treatment and / or prevention of cancer. The present invention also relates to pharmaceutical compositions comprising the novel therapeutic compounds defined herein, to processes for the synthesis of these compounds, and to their use for the treatment of diseases and / or conditions in which PiOI activity is involved. FUNDAMENTALS OF THE INVENTION

[002] Maintaining genome integrity is of paramount importance for cell survival, as genomic aberration is a major cause of disease, notably cancer1. The genome is continually challenged by various types of DNA damage, among which double-strand breaks (DSBs) are considered the most toxic, as they represent a source of dramatic genomic rearrangements if not repaired or if repaired inaccurately2.

[003] Theta DNA polymerase (P0I, encoded by POLQ) is a multifunctional enzyme comprising a C-terminal DNA polymerase domain, an N-terminal ATPase / helicase domain, and a less structured central domain with a protein interaction partner binding function3. Both enzymatic functions have been shown to have mechanistic activity in the DNA repair process. The helicase domain disrupts nucleofilament formation Rad51, removes RPA from single-stranded DNA, and stimulates ssDNA annealing. The polymerase domain extends the ends of single-stranded DNA to close ssDNA gaps. Petition 870250080361, dated 08 / 09 / 2025, page 283 / 513 / 231

[004] The expression of Ροϊθ is largely absent in normal cells, but expression has been shown to be upregulated in multiple cancers and increased expression correlates with poor prognosis4,5,6. In normal mammalian cells, Homologous Recombination (HR) and Non-Homologous End Joining (NHEJ) are the two main pathways for the faithful repair of DSBs. Other alternative pathways referred to as Alternative NHEJ (ALT-NHEJ) are also involved in DSB repair, mainly in the absence of HR and NHEJ, as supporting pathways7,4,8. The most defined ALT-NHEJ pathway is MicroHomology-Mediated End Joining (MMEJ), which relies on micro-homologies flanking the breaks to repair the lesion. In doing so, MMEJ inherently leads to deletions and therefore contributes to genomic instability9,10.ΡοΙΘ acts prominently in MMEJ which has been shown to process and anneal the ends of single-stranded DNA, as well as synthesize DNA to complete repair11, 12, 13.

[005] Deficiency in DNA Damage Response (DDR), such as loss of HR, results in genomic instability and is frequently associated with cancer. However, cancers with deficient DDR can become critically dependent on supporting DNA repair pathways, which present an Achilles' heel that can be targeted to eliminate cancer cells. For example, PARP1 inhibitors are selectively lethal in cancer cells deficient in HR components (e.g., ATM, BARD1, PALB2, BRCA1, BRCA2, etc.)14.

[006] Similarly, selective lethality is observed when Polθ functions are abolished in the context of HR and NHEJ deficiencies. MMEJ is rarely employed when HR and NHEJ are available15, but becomes necessary when canonical pathways are compromised during carcinogenesis, causing these cancer cells to become specifically dependent on Polθ4,16. Petition 870250080361, dated 08 / 09 / 2025, page 284 / 513 / 231

[007] PARP inhibitors are used in the treatment of HR-deficient cancers, but inherent or acquired drug resistance is a significant limitation. Two of the most frequent mechanisms of PARPi resistance could be neutralized by PARPi inhibition: (i) The main resistance mechanism, observed in clinical samples, is the reactivation of HR by the reversal of the mutation that caused the deficiency in HR17. It is believed that a significant proportion of such reversal mutations are acquired by the action of ΡοΙΘ in MMEJ18,19. (ii) Restoration of HR activity in BRCA1-deficient cancer by loss of the SHLD / 53BP1 complex has been shown to lead to resistance to PARP inhibitors20,21,22,23. It is predicted that PI inhibitors will be useful in the treatment of such tumors24 and deficiency in both the SHLD / 53BP1 complex and BRCA1 has been shown to result in vulnerability to PI inhibition25,26.

[008] In addition to the synthetic lethality observed in cancers deficient in HR and NHEJ, it has been reported that the loss of PiI sensitizes cancer cells to many standard care agents. PiI depletion leads to potentiation of several chemotherapies, such as topoisomerase inhibitors 1 / 227hydroxyurea, platinum agents28, bleomycin, as well as irradiation29,30. Furthermore, the loss of PiI has also been shown to intensify the effects of inhibitors targeting DNA repair: for example, PARP31, ATM27, ATR32 and DNAPK32.

[009] Considering the numerous evidences of sensitization to therapies associated with DNA repair, ΡοΙΘ represents a promising target for combination with already established agents that constitute standard of care.

[0010] There is therefore a need for new, improved agents capable of targeting PαοΙΘ and inhibiting its activity. Furthermore, there is a need for Petition 870250080361, dated 09 / 08 / 2025, p. 285 / 513 / 231 improved agents that possess one or more favorable pharmaceutical properties, such as, for example, improved potency, improved metabolic stability in humans, improved cell permeability, or improved sensitivity. The present invention was conceived with the foregoing in mind. References

[0011] 1. Helleday T., et al, Nat Rev Genet. (2014); 15:585-98 2. Ceccaldi R., et al, Trends Cell Biol. (2016); 26:52-64 3. Seki M. et al., Nucleic Acids Res., (2003); 31:6117-26 4. Ceccaldi R., et al., Nature (2015); 518:258-62 5. Lemée F., et al., PNAS (2010); 107:13390-5 6. Higgins GS, et al., Oncotarget (2010); 1:175-84 7. Kabotyanski EB, et al, Nucleic Acids Res. (1998); 26:5333-42 8. Ahrabi S., et al, Nucleic Acids Res. (2016); 44:5743-57 9. McVey M., et al., Trends Genet. (2008); 24:529-38 10. Sfeir A., ​​et al, Biochem Sci. (2015); 40:701-14) 11. Chan SH, et al., PLoS Genet. (2010); 6:e1001005 12. Wyatt DW, et al, Mol Cell. (2016); 63:662-673 13. Black SJ, et al., Nat Commun. (2019); 10:4423 14. Audeh MW, et al., Lancet (2010); 376 (9737):245-51 15. Truong W., et al., PNAS (2013); 110:7720-7725 16. Mateos-Gomez PA, et al., Nature (2015); 518:254-57 17. Noordermeer SM, et al., Trends Cell Biol. (2019); 29:820-834 18. Edwards SL, et al., Nature (2008); 451(7182):1111-5 19. Lukashchuk N., et al., J Clin Oncol (2022) 40(16_suppl):5559-5559) 20. Jaspers JE, et al., Cancer Discov. (2013); 3(1):68 Petição 870250080361, from 08 / 09 / 2025, pág. 286 / 513 / 231 21. Pettitt SJ, et al., Nat Commun. (2018); 9:1849; 22. Noordermeer SM, et al., Nature (2018) 560:117 23. Nacson J., et al, Cell Rep. (2018); 25(5):1384) 24. Higgins G., et al, Science (2018); 359(6381):1217-1218 25. Zatreanu D., et al, Nat Commun. (2021); 12(1):3636 26. Feng W., et al, Nat Commun. (2019); 10(1):4286 27. Wang ZI et al., J Biol Chem. 2019 Mar 15; 294(11): 39093919 28. Dai CH et al., Oncotarget. 2016; 7(40):65157-65170 29. Yousefzadeh MJ et al., PLoS Genet. 2014 Oct 2;10(10):e1004654 30. Higgins G et al. Cancer Res. 2010 Apr 1;70(7):2984-93 31. Schrempf et al., Trends Cancer. 2021;7(2):98-111 32. Kumar RJ et al., NAR Cancer. 2020 Dec; 2(4): zcaa038 SUMMARY OF THE INVENTION

[0012] In one aspect, the present invention provides a compound of Formula I, as defined herein, and / or a pharmaceutically acceptable salt, hydrate or solvate thereof.

[0013] In another aspect, the present invention provides a pharmaceutical composition comprising a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof and one or more pharmaceutically acceptable excipients.

[0014] In another aspect, the present invention provides a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, for use in therapy.

[0015] In another aspect, the present invention provides a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein. Petition 870250080361, dated 09 / 08 / 2025, p. 287 / 513 / 231 defined, for use in the treatment of a disease or condition in which the activity of ΡοΙΘ is implicated.

[0016] In another aspect, the present invention provides a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, for use in the treatment of a disease or condition associated with abnormal activity of ΡοΙΘ.

[0017] In another aspect, the present invention provides a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, for use in the treatment of cancer or benign neoplasms.

[0018] In another aspect, the present invention provides a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, for use in the treatment of cancer.

[0019] In another aspect, the present invention provides the use of a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for use in the treatment of a disease or condition in which the activity of ΡοΙΘ is implicated.

[0020] In another aspect, the present invention provides the use of a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for use in the treatment of a disease or condition associated with abnormal activity of P₂O₅.

[0021] In another aspect, the present invention provides the use of a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for use in the treatment of cancer or benign neoplasms. Petition 870250080361, dated 09 / 08 / 2025, p. 288 / 513 / 231

[0022] In another aspect, the present invention involves the use of a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for use in the treatment of cancer.

[0023] In another aspect, the present invention provides a method for treating a disease or condition in which the activity of ΡοΙΘ is involved, said method comprising administering to an individual in need thereof an effective amount of a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or of a pharmaceutical composition as defined herein.

[0024] In another aspect, the present invention provides a method for treating a disease or condition associated with abnormal activity of ΡοΙΘ, said method comprising administering to an individual in need thereof an effective amount of a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or of a pharmaceutical composition as defined herein.

[0025] In another aspect, the present invention provides a method for the treatment of cancer or benign neoplasms, said method comprising administering to an individual in need thereof an effective amount of a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or of a pharmaceutical composition as defined herein.

[0026] In another aspect, the present invention provides a method for the treatment of cancer, said method comprising administering to an individual in need thereof an effective amount of a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or of a pharmaceutical composition as defined herein.

[0027] In another aspect, the present invention provides a treatment Petition 870250080361, dated 09 / 08 / 2025, p. 289 / 513 / 231 combined comprising a compound of Formula I, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein, with one or more additional therapeutic agents.

[0028] In another aspect, the present invention provides a process for the preparation of compounds of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein, with one or more additional therapeutic agents.

[0029] In a further aspect, the present invention provides the use of a compound of Formula I or a salt, hydrate or solvate thereof, for CRISPR-mediated gene editing in vitro or in vivo.

[0030] In another aspect, the present invention provides the use of a compound of Formula I or a salt, hydrate or solvate thereof, to increase the efficiency of CRISPR gene editing in vitro or in vivo.

[0031] In another aspect, the present invention provides a compound of Formula I, or a salt, hydrate or solvate thereof, for use in CRISPR gene editing in vivo.

[0032] In another aspect, the present invention provides a compound of Formula I, or a salt, hydrate or solvate thereof, for use in increasing the efficiency of CRISPR gene editing in vivo.

[0033] Preferred, suitable and optional features of any particular aspect of the present invention are also preferred, suitable and optional features of any other aspect. DETAILED DESCRIPTION OF THE INVENTION Definitions

[0034] Unless otherwise specified, the following terms, as used in the descriptive report and claims, have the following meanings set forth below.

[0035] It should be recognized that references to “treat” or “treatment” include prophylaxis as well as relief of established symptoms. Petition 870250080361, dated 09 / 08 / 2025, p. 290 / 513 / 231 of a condition. “Treating” or “treatment” of a state, disorder or condition therefore includes: (1) preventing or delaying the appearance of clinical symptoms of the state, disorder or condition that develop in a human who may be affected or predisposed to the state, disorder or condition, but who does not yet present or exhibit clinical or subclinical symptoms of the state, disorder or condition, (2) inhibiting the state, disorder or condition, that is, interrupting, reducing or delaying the development of the disease or a recurrence thereof (in the case of maintenance treatment) or at least one clinical or subclinical symptom thereof or (3) alleviating or attenuating the disease, that is, causing the regression of the state, disorder or condition or at least one of its clinical or subclinical symptoms.

[0036] A “therapeutically effective amount” means the amount of a compound which, when administered to a mammal for the treatment of a disease, is sufficient to effect such treatment for the disease. The “therapeutically effective amount” will vary depending on the compound, the disease and its severity, and the age, weight, etc. of the mammal being treated.

[0037] References to “PΡοΙΘ” refer to theta DNA polymerase (encoded by POLQ).

[0038] The compounds and intermediates described herein may be named according to the IUPAC (International Union for Pure and Applied Chemistry) or CAS (Chemical Abstracts Service) nomenclature systems. It should be understood that, unless expressly specified otherwise, the terms “Formula I compounds”, “compounds of the invention” and the more general term “compounds” refer to and include any and all compounds described by and with reference to Formula I of this document. It should also be understood that these terms encompass all stereoisomers, i.e., cis and trans isomers, as well as optical isomers, i.e., Petition 870250080361, dated 09 / 08 / 2025, p. 291 / 513 / 231 R and S enantiomers of such compounds, in substantially pure form and / or any mixtures thereof in any proportion. This understanding extends to pharmaceutical compositions and treatment methods employing or comprising one or more compounds of Formula I, either alone or in combination with additional agents.

[0039] Unless otherwise specified, atoms are referred to herein by their chemical symbols as listed in the IUPAC Periodic Table of Elements. For example, “C” refers to a carbon atom.

[0040] The term “(m-nC)” or “(m-nC) group”, used alone or as a prefix, refers to any group having man carbon atoms.

[0041] In this descriptive report, the term “alkyl” includes both straight-chain and branched-chain alkyl groups. References to individual alkyl groups, such as “propyl,” are specific only to the straight-chain version, and references to individual branched-chain alkyl groups, such as “isopropyl,” are specific only to the branched-chain version. For example, “(1-6C) alkyl” includes (1-4C) alkyl, (1-3C) alkyl, propyl, isopropyl, and t-butyl. A similar convention applies to other radicals, for example, “1-6C phenyl alkyl” includes (1-4C) phenyl alkyl, benzyl, 1-phenylethyl, and 2-phenylethyl.

[0042] An “alkylene” group is an alkyl group that is positioned between and serves to connect two other chemical groups. Thus, “alkylene(1-6C)” means a linear saturated divalent hydrocarbon radical of one to six carbon atoms or a branched saturated divalent hydrocarbon radical of three to six carbon atoms, for example, methylene, ethylene, propylene, 2-methylpropylene, pentylene and the like.

[0043] “Cycloalkyl(3-6C)” means a hydrocarbon ring containing from 3 to 6 carbon atoms, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or bicyclo[2.2.1]heptyl. Petition 870250080361, dated 08 / 09 / 2025, pages 292 / 513 / 231

[0044] The term “halo” or “halogen” refers to fluorine, chlorine, bromine, and iodine.

[0045] In this descriptive report, alone or together with another term or terms, “haloalkyl” and “haloalkyl group” refer to alkyl groups in which one or more hydrogen atoms are replaced by halogen atoms. Representative examples include, but are not limited to, CF3, -CHF2, -CH2F, -CF2CF3, -CHFCF3 and -CH2CF3. Suitably, a haloalkyl group is selected from -CHF2 and -CF3, suitably -CF3.

[0046] In this descriptive report, alone or together with another term or terms, “haloalkoxy” and “haloalkoxy group” refer to alkoxy groups (i.e., O-alkyl groups) in which one or more hydrogen atoms are replaced by halogen atoms. Representative examples include, but are not limited to, -OCF3, -OCHF2, -OCH2F, and -OCF2CF3. Appropriately, a haloalkoxy group is selected from among -OCHF2 and -OCF3, appropriately OCF3.

[0047] The term “heterocyclic”, “heterocyclic” or “heterocycle” means one or more non-aromatic, saturated or partially saturated, fused, bridging or spiro monocyclic heterocyclic ring systems. Monocyclic heterocyclic rings contain from about 3 to 12 (suitably 3 to 7) ring atoms, containing from 1 to 5 (suitably 1, 2 or 3) heteroatoms selected from nitrogen, oxygen or sulfur in the ring. Bicyclic heterocycles contain from 7 to 17 member atoms, suitably 7 to 12 member atoms, in the ring. Bicyclic heterocyclic ring(s) may be fused, spiro or bridging ring systems. Examples of heterocyclic groups include cyclic ethers such as, among others, oxanyl, oxetanyl, tetrahydrofuranyl, dioxanyl, and substituted cyclic ethers. Nitrogen-containing heterocycles include, for example, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, tetrahydrotriazinyl, tetrahydropyrazolyl, and the like.Typical heterocycles containing sulfur. Petition 870250080361, dated 09 / 08 / 2025, p. 293 / 513 / 231, includes tetrahydrothienyl, dihydro-1,3-dithiol, tetrahydro-2H-thiopyran, and hexahydrothiepin. Other heterocycles include dihydro-oxathiolyl, tetrahydrooxazolyl, tetrahydro-oxadiazolyl, tetrahydrodioxazolyl, tetrahydrooxatiazolyl, hexahydrotriazinyl, tetrahydro-oxazinyl, morpholinyl, thiomorpholinyl, tetrahydropyrimidinyl, dioxolinyl, octahydrobenzofuranyl, octahydrobenzimidazolyl, and octahydrobenzothiazolyl. For heterocycles containing sulfur, heterocycles with oxidized sulfur containing SO or SO2 groups are also included. Examples include the sulfoxide and sulfone forms of tetrahydrothienyl and thiomorpholinyl compounds, such as, among others, tetrahydrothiene 1,1-dioxide and thiomorpholinyl 1,1-dioxide.A suitable value for a heterocyclyl group carrying 1 or 2 oxo (=O) or thioxo (=S) substituents is, for example, 2-oxopyrrolidinyl, 2-thioxopyrrolidinyl, 2-oxoimidazolidinyl, 2-thioxoimidazolidinyl, 2-oxopiperidinyl, 2,5-dioxopyrrolidinyl, 2,5-dioxoimidazolidinyl or 2,6-dioxopiperidinyl. Specific heterocyclyl groups are saturated monocyclic heterocyclides of 3 to 7 members containing 1, 2, or 3 heteroatoms selected from nitrogen, oxygen, or sulfur, for example, azetidinyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, morpholinyl, tetrahydrothienyl, tetrahydrothienyl 1,1-dioxide of tetrahydrothienyl, thiomorpholinyl, thiomorpholinyl 1,1-dioxide of piperidinyl, homopiperidinyl, piperazinyl, or homopiperazinyl. As a person skilled in the art would recognize, any heterocycle can be linked to other groups via any suitable atom, such as a carbon or nitrogen atom.However, the reference here to piperidino or morpholino refers to a piperidin-1-yl or morpholin-4-yl ring that is linked through the ring nitrogen.

[0048] By “bridging ring systems,” we mean ring systems in which two rings share more than two atoms; see, for example, Advanced Organic Chemistry, by Jerry March, 4th Edition, Wiley Interscience, pages 131-133, 1992. Examples of ring systems Petition 870250080361, dated 09 / 08 / 2025, p. 294 / 513 / 231 bridging heterocyclines include aza-bicyclo[2.2.1]heptane, 2-oxa-5-azabicyclo[2.2.1]heptane, aza-bicyclo[2.2.2]octane, aza-bicyclo[3.2.1]octane and quinuclidine.

[0049] By “spirobicyclic ring systems” it is understood that the two ring systems share a common spiro carbon atom, that is, the heterocyclic ring is linked to one more carbocyclic or heterocyclic ring through a single common spiro carbon atom. Examples of spiro ring systems include 6-azaspiro[3.4]octane, 2-oxa-6azaspiro[3.4]octane, 2-azaspiro[3.3]heptanes, 2-oxa-6-azaspiro[3.3]heptanes, 7-oxa-2-azaspiro[3.5]nonane, 6-oxa-2-azaspiro[3.4]octane, 2-oxa-7azaspiro[3.5]nonane and 2-oxa-6-azaspiro[3.5]nonane.

[0050] The term “heteroaryl” or “heteroaromatic” means a mono-, bi-, or polycyclic aromatic ring incorporating one or more (e.g., 14, particularly 1, 2, or 3) heteroatoms selected from nitrogen, oxygen, or sulfur. The term heteroaryl includes both monovalent and bivalent species. Examples of heteroaryl groups are monocyclic and bicyclic groups containing five to twelve members in the ring and, more commonly, five to ten members in the ring. The heteroaryl group may be, for example, a 5- or 6-membered monocyclic ring or a 9- or 10-membered bicyclic ring, for example, a bicyclic structure formed by fused five- and six-membered rings or two fused six-membered rings. Each ring may contain up to about four heteroatoms, typically selected from nitrogen, sulfur, and oxygen. Typically, the heteroaryl ring will contain up to 3 heteroatoms, more commonly up to 2, for example, a single heteroatom.In one embodiment, the heteroaryl ring contains at least one nitrogen atom in the ring. The nitrogen atoms in heteroaryl rings can be basic, as in the case of an imidazole or a pyridine, or essentially non-basic, as in the case of a nitrogen in indole or pyrrole. In general, the number of basic nitrogen atoms... Petition 870250080361, dated 08 / 09 / 2025, page 295 / 513 / 231 present in the heteroaryl group, including any substituents in the amino group of the ring, will be less than five.

[0051] . benzotiazolila, benzotiazolila, indazolila, purinila, benzofurazanila, quinolila, isoquinolila, quinazolinila, quinoxalinila, cinolinila, pteridinila, naftiridinila, carbazolila, phenazinila, benzisoquinolinila, piridopirazinila, tieno[2,3b]-furanil-, 2H-furo[3,2b]piranil-, 5H-pirido[2,3-d]-oxazinil-, 1H-pirazol[4,3-d]-oxazolila, 4Himidazo[4,5d]thiazolila, pirazino[2,3d]piridazinila, -imidazo[2,1b]thiazolila, imidazo[1,2b][1,2,4]-triazinila."Heteroaryl" also encompasses partially aromatic bi- or polycyclic ring systems, wherein at least one ring is an aromatic ring and one or more of the other rings is a non-aromatic ring, saturated or partially saturated, provided that at least one ring contains one or more heteroatoms selected from nitrogen, oxygen, or sulfur. Examples of partially aromatic heteroaryl groups include, for example, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 2-oxo-1,2,3,4-tetrahydroquinolinyl, dihydrobenzthienyl, dihydrobenzfuranyl, 2,3-dihydrobenzo[1,4]dioxinyl, benzo[1,3]dioxyl, 2,2-dioxo-1,3-dihydro-2-benzothienyl, 4,5,6,7-tetrahydrobenzofuranyl, indolinyl. 1,2,3,4-tetrahydro-1,8-naphthyridinyl, 1,2,3,4-tetrahydropyrido[2,3-b]pyrazinyl, 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl and 6,8-dihydro-5H[1,2,4]triazol[4,3-a]pyrazinyl.

[0052] Examples of five-membered heteroaryl groups include, among others, pyrrolyl, furanyl, thienyl, imidazolyl, furazanyl, oxazolyl, oxadiazolyl, oxatriazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, triazolyl and tetrazolyl groups. Petition 870250080361, dated 08 / 09 / 2025, page 296 / 513 / 231

[0053] Examples of six-membered heteroaryl groups include, among others, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, and triazinyl.

[0054] Heteroaryl groups include ring systems such as pyridones, which can exist in heteroaromatic form, as illustrated below.

[0055] A bicyclic heteroaryl group can be, for example, a group selected from: a benzene ring fused to a 5- or 6-membered ring containing 1, 2, or 3 heteroatoms in the ring; a pyridine ring fused to a 5- or 6-membered ring containing 1, 2, or 3 heteroatoms in the ring; a pyrimidine ring fused to a 5- or 6-membered ring containing 1 or 2 heteroatoms in the ring; a pyrrole ring fused to a 5- or 6-membered ring containing 1, 2, or 3 heteroatoms in the ring; a pyrazole ring fused to a 5- or 6-membered ring containing 1 or 2 heteroatoms in the ring; a pyrazine ring fused to a 5- or 6-membered ring containing 1 or 2 heteroatoms in the ring; an imidazole ring fused to a 5- or 6-membered ring containing 1 or 2 heteroatoms in the ring; an oxazole ring fused to a 5- or 6-membered ring containing 1 or 2 heteroatoms in the ring; an isoxazole ring fused to a 5- or 6-membered ring containing 1 or 2 heteroatoms in the ring; a thiazole ring fused to a 5- or 6-membered ring containing Petition 870250080361, dated 08 / 09 / 2025, page 297 / 513 / 231 or 2 heteroatoms in the ring; an isothiazole ring fused to a 5- or 6-membered ring containing 1 or 2 heteroatoms in the ring; a thiophene ring fused to a 5- or 6-membered ring containing 1, 2, or 3 heteroatoms in the ring; a furan ring fused to a 5- or 6-membered ring containing 1, 2, or 3 heteroatoms in the ring; a cyclohexyl ring fused to a 5- or 6-membered heteroaromatic ring containing 1, 2, or 3 heteroatoms in the ring; and a cyclopentyl ring fused to a 5- or 6-membered heteroaromatic ring containing 1, 2, or 3 heteroatoms in the ring.

[0056] Specific examples of bicyclic heteroaryl groups containing a six-membered ring fused to a five-membered ring include, among others, benzfuranyl, benzthiophenyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzthiazolyl, benzisothiazolyl, isobenzofuranyl, indolyl, isoindolyl, indolizinyl, indolinyl, isoindolinyl, purinyl (e.g., adeninyl, guaninyl), indazolyl, benzodioxyl, and pyrazolpyridinyl groups.

[0057] Specific examples of bicyclic heteroaryl groups containing two fused six-membered rings include, among others, quinolinyl, isoquinolinyl, cromanyl, thiocromanyl, chromenyl, isochromenyl, cromanyl, isocromanyl, benzodioxanyl, quinolizinyl, benzoxazinyl, benzodiazinyl, pyridopyridinyl, quinoxalinyl, quinazolinyl, cinolinyl, phthalazinyl, naphthyridinyl and pteridinyl groups.

[0058] The term “aryl” means a cyclic or polycyclic aromatic ring containing from 5 to 12 carbon atoms. The term aryl includes both monovalent and divalent species. Examples of aryl groups include, among others, phenyl, biphenyl, naphthyl and the like. In a particular embodiment, an aryl is phenyl. Petition 870250080361, dated 08 / 09 / 2025, page 298 / 513 / 231

[0059] This descriptive report also makes use of several compound terms to describe groups comprising more than one functionality. Such terms will be understood by those skilled in the art. For example, heterocyclyl-alkyl(m-nC) comprises alkyl(m-nC) substituted by heterocyclyl.

[0060] The term “aryl-alkyl(1-2C)” means an aryl group covalently bonded to an alkylene(1-2C) group, both of which are defined herein. Examples of aryl-alkyl(1-2C) groups include benzyl, phenylethyl and the like.

[0061] “Heteroaryl-alkyl(1-3C)” means a heteroaryl group covalently linked to an alkylene(1-3C) group, both of which are defined herein. Examples of heteroaryl-alkyl groups include pyridine-3-ylmethyl, 2-(benzofuran-2-yl)ethyl and the like.

[0062] “Heterocyclyl-alkyl(1-2C)” means a heterocyclyl group covalently bonded to an alkylene(1-2C) group, both of which are defined herein.

[0063] “Cycloalkyl(3-6C)-alkyl(1-2C)” means a cycloalkyl(3-6C) group covalently bonded to an alkylene(1-2C) group, both of which are defined herein.

[0064] The term “optionally substituted” refers to groups, structures or molecules that are substituted and those that are not substituted. The term “wherein any CH, CH2, CH3 group or heteroatom (i.e., NH) within an R1 group is optionally substituted” properly means that (any) one of the hydrogen radicals of the R1 group is substituted by a relevant stipulated group.

[0065] When optional substituents are chosen from “one or more” groups, it should be understood that this definition includes all substituents that are chosen from one of the specified groups or substituents that are chosen from two or more of the groups. Petition 870250080361, dated 09 / 08 / 2025, p. 299 / 513 / 231 specified.

[0066] A wavy connection () is used here to show a connection point.

[0067] The term “compound of the invention” means those compounds that are described herein, both generically and specifically.

[0068] In this descriptive report, by itself or together with another term or terms, “pharmaceutically acceptable” refers to materials that are generally chemically and / or physically compatible with other ingredients (such as, for example, when referring to a formulation) and / or are generally physiologically compatible with the recipient (such as, for example, an individual) thereof.

[0069] In this descriptive report, alone or together with another term or terms, “individual(s)” and “patient(s)” properly refer to mammals, in particular humans. Compounds of the invention

[0070] In a first aspect, the present invention relates to a compound, or pharmaceutically acceptable salt thereof, having the structural formula I shown below: (I) where: Ring A is selected from the group consisting of a phenyl and a heteroaryl group of 5 to 10 members; R1 is selected from the group consisting of phenyl, 5- to 6-membered heteroaryl, 5- to 6-membered heterocyclyl, heterocyclyl Petition 870250080361, dated 09 / 08 / 2025, p. 300 / 513 / 231 bicyclic with 6 to 10 members, bridging heterocycline with 6 to 10 members and spiro-heterocycline with 6 to 12 members, where: (i) R1 is optionally substituted with one or more R100 substituents; or two R100 substituents on adjacent atoms in the ring at R1 may be linked to form a fused cycloalkyl(3-6C) ring; or (ii) when it is a 5- to 6-membered heterocyclyle, a 6- to 10-membered bicyclic heterocyclyle, a 6- to 10-membered bridging heterocyclyle, and a 6- to 12-membered spiro-heterocyclyle, R1 is optionally substituted with oxo; and wherein R100 is selected from the group consisting of halo, alkyl(1-4C), haloalkyl(1-4C), haloalkoxy(1-4C), cycloalkyl(3-6C), cycloalkyloxy(3-6C), -Q100-OH, -Q100-O-alkyl(1-4C), -C(O)-alkyl(1-4C) and -Q100-cyano; where Q100 is a (1-4C) alkylene or alkylene bond; The integers a and b are each independently either 0 or 1; R2 and R3, when present, are selected, each independently, from the group consisting of halo, cyano, alkyl(1-4C), alkoxy(1-4C), haloalkyl(1-4C), hydroxyalkyl(1-4C), haloalkoxy(1-4C), -Q1-O-alkyl(1-4C) and -C(O)OH, wherein Q1 is a linkage or alkylene(1-4C); X4 is selected from either CRx4 or N; X5 is selected from either CRx5 or N; X6 is selected from either CRx6 or N; X7 is selected from either CRx7 or N; Rx4 is hydrogen, fluorine, chlorine, methyl, or a group of the formula: -YQ where: Y is -O-, -S-, -NH- or -CH2-; Q is selected from hydrogen, alkyl(1-6C), Petition 870250080361, dated 08 / 09 / 2025, page 301 / 513 / 231 cycloalkyl(3-8C), phenyl, heteroaryl, 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl and 6- to 12-membered spiroheterocyclyl, wherein each of the same is optionally substituted by one or more R100 substituents and a cycloalkyl(3-8C), 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl and 6- to 12-membered spiroheterocyclyl is optionally substituted by oxo; Rx5 or Rx6 are selected from: hydrogen, halo, cyano, nitro, or a group of the formula: -L1-Y1-L2-Q1 where: L1 is absent or alkylene(1-2C); Y1 is absent or -O-, -S-, -SO-, -SO2-, -S(O)(=NRy1)-, -N(Ry1)-, -C(O)-, -C(O)O-, -OC(O)-, -C(O)N(Ry1)-, -N(Ry1)C(O)-, -S(O)2N(Ry1)-, N(Ry1)SO2- or -N(Ry1a)C(O)-N(Ry1)-, wherein Ry1 and Ry1a are selected from hydrogen or (1-2C) alkyl; L2 is absent or alkylene(1-2C); and Q1 is hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (26C), cycloalkyl (3-8C), phenyl, 5- to 6-membered heteroaryl, 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl, and 6- to 12-membered spiroheterocyclyl, wherein: (i) when it is alkyl(1-6C), alkenyl(2-6C) or alkynyl(2-6C), Q1 is optionally further replaced by one or more substituent groups selected independently from oxo, halo, cyano or by one or more groups of the formula: -Y2-Q2 where: Y2 is absent or selected from -O-, -S-, -SO-, -SO2-, Petition 870250080361, dated 09 / 08 / 2025, p. 302 / 513 / 231 N(Ry2)-, -C(O)-, -C(O)O-, -OC(O)-, -C(O)N(Ry2)-, -N(Ry2)C(O)-, S(O)2N(Ry2)- or -N(Ry2)SO2-, wherein Ry2 is selected from hydrogen or (1-2C) alkyl; Q2 is selected from: hydrogen; an alkyl(1-4C) group that is optionally substituted with one or more substituents selected from halo, hydroxy, cyano, amino or alkoxy(1-4C); or a 4- to 7-membered heterocyclic ring that is optionally substituted with one or more substituents selected from halo, hydroxy, cyano, amino, alkyl(1-4C) or alkoxy(1-4C); (ii) when it is a cycloalkyl(3-8C), 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl and 6- to 12-membered spiro-heterocyclyl, Q1 is optionally further substituted by one or more substituent groups selected independently from oxo, halo, cyano or by one or more groups of the formula: -Y3-Q3 where: Y3 is absent or selected from either -O-, -S-, -SO-, -SO2-, N(Ry2)-, -C(O)-, -C(O)O-, -OC(O)-, -C(O)N(Ry3)-, -N(Ry3)C(O)-, S(O)2N(Ry3)- or -N(Ry3)SO2-, wherein Ry3 is selected from hydrogen or (1-2C) alkyl; Q3 is selected from: hydrogen; an alkyl(1-4C) group that is optionally substituted with one or more substituents selected from halo, hydroxy, cyano, amino, or alkoxy(14C); or a 4- to 7-membered heterocyclic ring that is optionally Petition 870250080361, dated 08 / 09 / 2025, page 303 / 513 / 231 replaced by one or more substituents selected from halo, hydroxy, cyano, amino, alkyl(1-4C) or alkoxy(1-4C); (iii) when it is 5- to 6-membered phenyl or heteroaryl, Qi is optionally further replaced by one or more substituent groups selected independently from halo, cyano or by one or more groups of the -Y3-Q3 formula defined above; Rx7 is selected from hydrogen, fluorine, chlorine, hydroxyl, NH2, methyl or CF3; or Rx4 and Rx5, Rx5 and Rx6 or Rx6 and Rx7 are linked in such a way that, together with the carbon atoms to which they are attached, they form a fused cycloalkyl(5-6C), phenyl, 5- or 6-membered heteroaryl or 5- or 6-membered heterocyclic ring, wherein each of them is optionally substituted with fluorine, chlorine, methyl or hydroxyl; on the condition that: (i) when X5 is CRx5 and Rx5 is a group of the formula -L1-Y1L2-Q1, Xó is then selected from N, CH, CF, C-CN, C-Cl or C-Me; and (ii) when X6 is CRx6 and Rx6 is a group of the formula -L1-Y1L2-Q1, X5 is then selected from N, CH, CF, C-CN, C-Cl or C-Me.

[0071] In another aspect, the present invention relates to a compound, or pharmaceutically acceptable salt thereof, having the structural formula I shown below: ili (I) where: Ring A is selected from the group consisting of phenyl and Petition 870250080361, dated 09 / 08 / 2025, p. 304 / 513 / 231 a heterosexual group of 5 to 10 members; Ri is selected from the group consisting of phenyl, 5- to 6-membered heteroaryl, 5- to 6-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl, and 6- to 12-membered spiro-heterocyclyl, where: (i) R1 is optionally substituted with one or more R100 substituents; or two R100 substituents on adjacent atoms in the ring at R1 may be linked to form a fused cycloalkyl(3-6C) ring; or (ii) when it is a 5- to 6-membered heterocyclyle, a 6- to 10-membered bicyclic heterocyclyle, a 6- to 10-membered bridging heterocyclyle, and a 6- to 12-membered spiro-heterocyclyle, R1 is optionally substituted with oxo; and wherein R100 is selected from the group consisting of halo, alkyl(1-4C), haloalkyl(1-4C), haloalkoxy(1-4C), cycloalkyl(3-6C), cycloalkyloxy(3-6C), -Q100-OH, -Q1oo-O-alkyl(1-4C), -C(O)-alkyl(1-4C) and -Q1oo-cyano; wherein Q100 is a (1-4C) alkylene or alkylene group; The integers a and b are, each independently, either 0 or 1; R2 and R3, when present, are selected, each independently, from the group consisting of halo, cyano, -O-, alkyl(1-4C), alkoxy(1-4C), haloalkyl(1-4C), hydroxyalkyl(1-4C), haloalkoxy(1-4C), -Q1-O-alkyl(1-4C), -C(O)OH, -Q1-C(O)-NH2, -Q1-C(O)NHMe and -Q1-C(O)-NMe2, where Q1 is a (1-4C) alkylene or bond; X4 is selected from either CRx4 or N; X5 is selected from either CRx5 or N; X6 is selected from either CRx6 or N; X7 is selected from either CRx7 or N; Rx4 is hydrogen, fluorine, chlorine, methyl, or a group of the formula: -YQ Petition 870250080361, dated 09 / 08 / 2025, p. 305 / 513 / 231 in which: Y is -O-, -O-CH2-, -S-, -NH-, -CH2- or -CH2-CH2-; Q is selected from hydrogen, alkyl(1-6C), -C(O)-NH2, -C(O)-NHMe, -C(O)-NMe2, cycloalkyl(3-8C), phenyl, heteroaryl, 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl and 6- to 12-membered spiro-heterocyclyl, wherein each of these is optionally substituted by one or more R100 substituents and a cycloalkyl(3-8C), 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl and 6- to 12-membered spiro-heterocyclyl is optionally substituted by oxo; Rx5 or Rx6 are selected from: hydrogen, halo, cyano, nitro or a group of the formula: -L1-Y1-L2-Q1 where: L1 is absent or alkylene(1-2C); Y1 is absent or -O-, -S-, -SO-, -SO2-, -S(O)(=NRy1)-, -N(Ry1)-, -C(O)-, -C(O)O-, -OC(O)-, -C(O)N(Ry1)-, -N(Ry1)C(O)-, -S(O)2N(Ry1)-, N(Ry1)SO2- or -N(Ry1a)C(O)-N(Ry1)-, wherein Ry1 and Ry1a are selected from hydrogen or (1-2C) alkyl; L2 is absent or alkylene(1-2C); and Q1 is hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (26C), cycloalkyl (3-8C), phenyl, 5- to 6-membered heteroaryl, 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl, and 6- to 12-membered spiroheterocyclyl, wherein: (i) when it is alkyl(1-6C), alkenyl(2-6C) or alkynyl(2-6C), Q1 is optionally further substituted by one or more substituent groups selected independently from oxo, halo, cyano or by one or more Petition 870250080361, dated 09 / 08 / 2025, p. 306 / 513 / 231 groups of the formula: -Y2-Q2 where: Y2 is absent or selected from either -O-, -S-, -SO-, -SO2-, N(Ry2)-, -C(O)-, -C(O)O-, -OC(O)-, -C(O)N(Ry2)-, -N(Ry2)C(O)-, S(O)2N(Ry2)- or -N(Ry2)SO2-, wherein Ry2 is selected from hydrogen or (1-2C) alkyl; Q2 is selected from: hydrogen; an alkyl(1-4C) group that is optionally substituted with one or more substituents selected from halo, hydroxy, cyano, amino or alkoxy(1-4C); or a 4- to 7-membered heterocyclic ring that is optionally substituted with one or more substituents selected from halo, hydroxy, cyano, amino, alkyl(1-4C) or alkoxy(1-4C); (ii) when it is a cycloalkyl(3-8C), 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl and 6- to 12-membered spiro-heterocyclyl, Q1 is optionally further substituted by one or more substituent groups selected independently from oxo, halo, cyano or by one or more groups of the formula: -Y3-Q3 where: Y3 is absent or selected from either -O-, -S-, -SO-, -SO2-, N(Ry2)-, -C(O)-, -C(O)O-, -OC(O)-, -C(O)N(Ry3)-, -N(Ry3)C(O)-, S(O)2N(Ry3)- or -N(Ry3)SO2-, wherein Ry3 is selected from hydrogen or (1-2C) alkyl; Q3 is selected from: hydrogen; Petition 870250080361, dated 08 / 09 / 2025, page 307 / 513 / 231 an alkyl(1-4C) group that is optionally substituted with one or more substituents selected from halo, hydroxy, cyano, amino or alkoxy(1-4C); or a 4- to 7-membered heterocyclic ring that is optionally substituted with one or more substituents selected from halo, hydroxy, cyano, amino, alkyl(1-4C) or alkoxy(1-4C); (iii) when it is 5- to 6-membered phenyl or heteroaryl, Qi is optionally further replaced by one or more substituent groups selected independently from halo, cyano or by one or more groups of the -Y3-Q3 formula defined above; Rx7 is selected from hydrogen, fluorine, chlorine, hydroxyl, NH2, methyl or CF3; or Rx4 and Rx5, Rx5 and Rx6 or Rx6 and Rx7 are linked in such a way that, together with the carbon atoms to which they are attached, they form a fused cycloalkyl(5-6C), phenyl, 5- or 6-membered heteroaryl or 5- or 6-membered heterocyclic ring, wherein each of these is optionally substituted with fluorine, chlorine, methyl or hydroxyl; on the condition that: (i) when X5 is CRx5 and Rx5 is a group of the formula -L1-Y1L2-Q1, X6 is then selected from N, CH, CF, C-CN, C-Cl or C-Me; and (ii) when X6 is CRx6 and Rx6 is a group of the formula -L1-Y1L2-Q1, X5 is then selected from N, CH, CF, C-CN, C-Cl or C-Me.

[0072] Appropriately, when X5 is CRx5 and Rx5 is cyan or a group of the formula -L1-Y1-L2-Q1, then: X4 is selected from N, CH, CF, C-Cl or C-Me; X6 is selected from N, CH, CF, C-CN, C-Cl or C-Me; X7 is selected from N, CH, CF, C-Cl or C-Me.

[0073] In one embodiment, when X5 is CRx5 and Rx5 is cyan or a group of the formula -L1-Y1-L2-Q1, then: Petition 870250080361, dated 08 / 09 / 2025, page 308 / 513 / 231 X4 is selected from N, CH, or CF; Xô is selected from N, CH, CF, C-Cl or C-Me; X7 is selected from N, CH, or CF.

[0074] In a further embodiment, when X5 is CRX5 and RX5 is cyan or a group of the formula -L1-Y1-L2-Q1, then: X4 is selected from N or CH or CF; Xô is selected from N, CH, CF, C-Cl or C-Me; X7 is selected from either N or CH.

[0075] In an additional embodiment, when X5 is CRX5 and RX5 is cyan or a group of the formula -L1-Y1-L2-Q1, then: X4 is CH; Xô is selected from N, CH, CF, C-Cl or C-Me; X7 is selected from either N or CH. [007ô] In an additional embodiment, when X5 is CRX5 and RX5 is cyan or a group of the formula -L1-Y1-L2-Q1, then: X4 is CH; Xô is CH; X7 is N or CH.

[0077] In an additional embodiment, when X5 is CRX5 and RX5 is cyan or a group of the formula -L1-Y1-L2-Q1, then: X4 is CH; Xô is CH; X7 is CH.

[0078] Properly, when Xô is CRxô and Rxô is cyan or a group of the formula -L1-Y1-L2-Q1, then: X4 is selected from N, CH, or CF; X5 is selected from N, CH, CF, C-Cl or C-Me; X7 is selected from N, CH, or CF.

[0079] In one modality, when Xô is CRxô and Rxô is cyan or one Petition 870250080361, dated 08 / 09 / 2025, page 309 / 513 / 231 group of the formula -L1-Y1-L2-Q1, then: X4 is selected from N, CH, or CF; X5 is selected from N, CH, or CF; X7 is selected from N, CH, or CF.

[0080] In an additional embodiment, when X6 is CRx6 and Rx6 is cyan or a group of the formula -L1-Y1-L2-Q1, then: X4 is selected from N, CH, or CF; X5 is selected from N, CH, or CF; X7 is selected from N, CH, or CF.

[0081] In an additional embodiment, when X6 is CRx6 and Rx6 is cyan or a group of the formula -L1-Y1-L2-Q1, then: X4 is selected from either N or CH; X5 is selected from N, CH, or CF; X7 is selected from either N or CH.

[0082] In an additional embodiment, when X6 is CRx6 and Rx6 is cyan or a group of the formula -L1-Y1-L2-Q1, then: X4 is CH; X5 is selected from either N or CH; X7 is selected from either N or CH.

[0083] Particular compounds of the invention include, for example, compounds of Formula I, or pharmaceutically acceptable salts, hydrates and / or solvates thereof, wherein, unless otherwise specified, each of the following of the rings A, R1, R100, R2, R3, the integer a, the integer b, X4, X5, X6, X7, Rx4, Rx5, Rx6, Rx7, X8, the integer c, R100a, the integer d, R100b, the integer ee Riooc has any of the meanings defined herein above or are as defined in any of paragraphs (1) to (89) below: (1) ring A is selected from phenyl or heteroaryl groups of 5, 6, 9 or 10 members; Petition 870250080361, dated 09 / 08 / 2025, p. 310 / 513 / 231 (2) ring A is selected from 5 or 6 membered phenyl or heteroaryl; (3) ring A is selected from 6-membered phenyl or heteroaryl; (4) ring A is a heteroaryl of 5, 6, 9 or 10 members; (5) ring A is a 5 or 6 membered heteroaryl; (6) ring A is phenyl, pyridinyl, pyridazinyl, pyrimidinyl, imidazolyl, pyrazolyl, triazolyl, imidazo[l,2-a]pyridinyl, [l,2,3]triazol[l,5a]pyridinyl, imidazo[l,5-a]pyridinyl, pyrrol[2,3-b]pyridinyl, pyrrol[3,2b]pyridinyl, pyrazol[1,5-a]pyridinyl, [1,2,4]triazol[1,5-a]pyridinyl, 1,6naphthyridinyl, or 1,7-naphthyridinyl; (7) ring A is phenyl, pyridinyl, pyrimidinyl and imidazole[l,2- a]pyridinyl, 1,2,3-triazole, pyrazolyl, isoxazolyl, imidazo[1,5-a]pyridinyl; (8) ring A is phenyl, pyridinyl, pyrimidinyl and imidazole[l,2- a]pyridinyl; (9) ring A is phenyl or pyridyl; (10) ring A is phenyl; (11) ring A is pyridyl; (12) ring A is selected from: ; Petition 870250080361, dated 08 / 09 / 2025, page 311 / 513 / 231, which indicates the point of attachment to the amide group of formula I; and Ri, R2, R3, aeb are as defined herein; (13) ring A is selected from: where indicates the point of attachment to the amide group of formula I; and Ri, R2, R3, aeb are as defined herein; (14) ring A is selected from: or where indicates the point of attachment to the amide group of formula I; and Ri, R2, R3, aeb are as defined herein; (15) ring A is selected from: where indicates the point of attachment to the amide group of formula I; and Ri, R2, R3, aeb are as defined herein; (16) ring A is selected from: Ri jT J íi jR2nou1χΧ ; where indicates the point of attachment to the amide group of formula I; and Ri, R2, R3, aeb are as defined herein; (17) ring A is: Petition 870250080361, dated 09 / 08 / 2025, p. 312 / 513 / 231 R2 Ri where indicates the point of attachment to the amide group of formula I; and R1, R2, R3, a and b are as defined herein; (18) ring A is: where indicates the point of attachment to the amide group of formula I; and Ri, R2, R3, aeb are as defined herein; (19) Ri is selected from phenyl or a 5- to 6-membered heteroaryl, each of which is optionally substituted with one or more R100 as defined herein above and in any of paragraphs (25) to (31) below; or two R100 substituents on adjacent atoms in the ring on Ri may be linked to form a fused cycloalkyl(3-6C) ring; (20) R1 is selected from phenyl or a 6-membered heteroaryl, each of which is optionally substituted with one or more R100 as defined herein above and in any of paragraphs (25) to (31) below; or two R100 substituents on adjacent atoms in the ring at Ri may be linked to form a fused cycloalkyl(3-6C) ring; (21) R1 is a group of the formula: or in which: indicates the point of attachment to ring A of formula I; X8 is CH or N; R100a, R100b and Riooc are R100 substituent groups as defined herein before and in any of paragraphs (25) to (31) below; and Petition 870250080361, dated 09 / 08 / 2025, p. 313 / 513 / 231 the integers c, d and e are 0, 1 or 2; (22) Ri is a group of the formula: or in which: indicates the point of attachment to ring A of formula I; X8 is CH or N; Riooa, Rioob and Riooc are R100 substituent groups as defined herein above and in any of paragraphs (25) to (31) below; and the integers of e are 0 or 1; (23) R1 is a group of the formula: or in which: indicates the point of attachment to ring A of formula I; Rioob is methyl, fluorine, or chlorine; Riooc is fluorine or chlorine, especially fluorine; (24) Ri is a group of the formula: in which: indicates the point of attachment to ring A of formula I.

[0084] (25) Rioo is selected from halo, alkyl(1-3C), haloalkyl(1-3C), haloalkoxy(1-3C), cycloalkyl(3-6C), cycloalkyloxy(3-6C), Petition 870250080361, dated 08 / 09 / 2025, page 314 / 513 / 231 -Q100-OH, -Qioo-O-alkyl(1-3C), -C(O)-alkyl(1-3C) and -Qioo-cyano; wherein Q100 is a (1-3C)alkylene linkage; (26) R100 is selected from halo, alkyl(1-2C), haloalkyl(1-2C), haloalkoxy(1-2C), cycloalkyl(3-6C), cycloalkyloxy(3-6C), -Q100-OH, -Q100-O-alkyl(1-2C), -C(O)-alkyl(1-2C) and -Q100-cyano; wherein Q100 is a linkage or alkylene(1-2C); (27) R100 is selected from halo, alkyl(1-2C), fluoroalkyl(1-2C), fluoroalkoxy(1-2C), cycloalkyl(3-6C), cycloalkyloxy(36C), -Q100-OH, -Q100-O-alkyl(1-2C), -C(O)-alkyl(1-2C) and -Q100-cyano; wherein Q100 is a linkage or alkylene(1-2C); (28) R100 is selected from halo, alkyl(1-2C), fluoroalkyl(1-2C), -Q100-OH, -Q100-O-alkyl(1-2C), -C(O)-alkyl(1-2C) and Q100-cyano; wherein Q100 is a linkage or alkylene(1-2C); (29) R100 is selected from halo, alkyl(1-2C), fluoroalkyl(1-2C), -Q100-OH and -Q100-O-alkyl(1-2C); wherein Q100 is a linkage or alkylene(1-2C); (30) R100 is selected from fluoro, chlorine, alkyl(1-2C), fluoroalkyl(1-2C), -Q100-OH and -Q100-O-alkyl(1-2C); where Q100 is a linkage or alkylene(1-2C); (31) R100 is selected from fluorine, chlorine, methyl, fluoromethyl(1-2C) and -Q100-O-alkyl(1-2C); where Q100 is a linkage or methylene; (32) the integer a is 0 or 1 and the integer b is 0; (33) the integer a is 0 and the integer b is 0; (34) the integer a is 1 and the integer b is 0; (35) R2 and R3, when present, are selected, each independently, from the group consisting of fluorine, chlorine, alkyl(1-2C), alkoxy(1-2C), haloalkyl(1-2C), hydroxyalkyl(1-2C), haloalkoxy(1-2C), -Q1-O-alkyl(1-2C) and -C(O)OH, where Q1 is a linkage or alkylene(1- Petition 870250080361, dated 09 / 08 / 2025, p. 315 / 513 / 231 2C); (36) R2 and R3, when present, are selected, each independently, from the group consisting of fluorine, chlorine, alkyl(12C), alkoxy(1-2C) or haloalkyl(1-2C); (37) R2 and R3, when present, are selected, each independently, from the group consisting of fluorine, alkyl(1-2C) or alkoxy(1-2C); (38) R2 and R3, when present, are methyl; (39) X4 is selected from CRx4; X5 is selected from CRx5 or N; X6 is selected from CRx6; X7 is selected from CRx7 or N; wherein Rx4, Rx5, Rx6 and Rx7 are as defined herein before or Rx4 is as defined in any of paragraphs (50) to (58); Rx5 is as defined in any of paragraphs (59) to (62); Rx6 is as defined in any of paragraphs (59) to (62); or Rx7 is as defined in any of paragraphs (63) or (64); (40) X4 is selected from CRx4; X5 is selected from CRx5 or N; X6 is selected from CRx6; X7 is selected from CH or N; wherein Rx4, Rx5 and Rx6 are as defined herein before or Rx4 is as defined in any of paragraphs (50) to (58); Rx5 is as defined in any of paragraphs (59) to (62); or Rx6 is as defined in any of paragraphs (59) to (62); (41) X4 is selected from CH; X5 is selected from CRx5 or N; X6 is selected from CRx6; X7 is selected from CH or N; wherein Rx5 and Rx6 are as defined herein before or Rx5 is as defined in any of paragraphs (59) to (62) and Rx6 is as defined in any of paragraphs (59) to (62); (42) X4 is selected from CH; X5 is selected from CH or N; X6 is selected from CRx6; X7 is selected from CH or N; wherein Rx6 is as defined herein before or in any of the paragraphs (59) to Petition 870250080361, dated 08 / 09 / 2025, page 316 / 513 / 231 (62); (43) X4 is selected from CH; X5 is selected from CH; Xô is selected from CRxô; X7 is selected from CH or N; wherein Rx6 is as defined herein before or in any of paragraphs (59) to (62); (44) X4 is selected from CH; X5 is selected from CH or N; X6 is selected from CRx6; X7 is selected from CH; wherein Rx6 is as defined herein before or in any of paragraphs (59) to (62); (45) X4 is selected from CH; X5 is selected from CH; Xô is selected from CRxô; X7 is selected from CH; wherein Rx6 is as defined herein before or in any of paragraphs (59) to (62); (46) X4 is selected from CH; X5 is selected from N; Xô is selected from CRxô; X7 is selected from CH; wherein Rx6 is as defined herein before or in any of paragraphs (59) to (62); (47) X4 is selected from CH; X5 is selected from CH; X6 is selected from CRx6; X7 is selected from N; wherein Rx6 is as defined herein before or in any of paragraphs (59) to (62); (48) X4 is selected from CH; X5 is selected from N; X6 is selected from CRx6; X7 is selected from N; wherein Rx6 is as defined herein before or in any of paragraphs (59) to (62); (49) X4 is selected from CH or N; X5 is selected from CRx5; X6 is selected from CH or N; X7 is selected from CH or N; wherein Rx5 is as defined herein before or in any of paragraphs (59) to (62); (50) X4 is selected from CH; X5 is selected from CRx5; X6 is selected from CH; X7 is selected from CH; wherein Rx5 is as defined herein before or in any of paragraphs (59) to (62); (51) X4 is selected from CH; X5 is selected from CRx5; X6 is selected from N; X7 is selected from CH; wherein Rx5 is as defined herein before or in any of paragraphs (59) to (62); Petition 870250080361, dated 08 / 09 / 2025, page 317 / 513 / 231 (52) X4 is selected from CH; X5 is selected from CRx5; X6 is selected from CH; X7 is selected from N; wherein Rx5 is as defined herein before or in any of paragraphs (59) to (62); (53) X4 is selected from N; X5 is selected from CRx5; X6 is selected from CH; X7 is selected from CH; wherein Rx5 is as defined herein before or in any of paragraphs (59) to (62); (54) X4 is selected from N; X5 is selected from CRx5; X6 is selected from N; X7 is selected from CH; wherein Rx5 is as defined herein before or in any of paragraphs (59) to (62); (55) Rx4 is selected from hydrogen, fluorine, chlorine, methyl or a group of the formula: -YQ where: Y is -O-, -S-, -NH- or -CH2-; Q is selected from hydrogen, alkyl(1-4C), cycloalkyl(3-6C), phenyl, 5- or 6-membered heteroaryl, 4- to 7-membered heterocyclyl, wherein each of these is optionally substituted by one or more R100 substituents, and a cycloalkyl(3-8C) and 4- to 7-membered heterocyclyl is optionally substituted by oxo; (56) Rx4 is selected from hydrogen, fluorine, methyl or a group of the formula: -YQ where: Y is -O-, -S-, -NH- or -CH2-; Q is selected from hydrogen, alkyl (1-4C), cycloalkyl (3-6C), phenyl, 5- or 6-membered heteroaryl, 4- to 7-membered heterocyclyl; (57) Rx4 is selected from hydrogen, fluorine, chlorine or methyl; Petition 870250080361, dated 08 / 09 / 2025, page 318 / 513 / 231 (58) Rx4 is hydrogen; (59) Rx5 or Rx6 are selected from hydrogen, halo, cyano, nitro or a group of the formula: -L1-Y1-L2-Q1 where: L1 is absent or alkylene(1-2C); Y1 is absent or -O-, -S-, -SO-, -SO2-, -S(O)(=NRy1)-, -N(Ry1)-, -C(O)-, -C(O)O-, -OC(O)-, -C(O)N(Ry1)-, -N(Ry1)C(O)-, -S(O)2N(Ry1)-, N(Ry1)SO2- or -N(Ry1a)C(O)-N(Ry1)-, wherein Ry1 and Ry1a are selected from hydrogen or (1-2C) alkyl; L2 is absent or alkylene(1-2C); and Q1 is hydrogen, alkyl (1-6C), cycloalkyl (3-8C), phenyl, 5- to 6-membered heteroaryl, 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl, and 6- to 12-membered spiroheterocyclyl, wherein: (i) when it is alkyl(1-6C), Q1 is optionally further replaced by one or more substituent groups selected independently from oxo, halo, cyano or by one or more groups of the formula: -Y2-Q2 where: Y2 is absent or selected from either -O-, -SO2-, -N(Ry2)-, C(O)-, -C(O)N(Ry2)-, -N(Ry2)C(O)-, -S(O)2N(Ry2)- or -N(Ry2)SO2-, wherein Ry2 is selected from either hydrogen or methyl; Q2 is selected from: hydrogen; an alkyl(1-4C) group that is optionally substituted with one or more substituents selected from halo, hydroxy, cyano, amino or alkoxy(14C); or Petition 870250080361, dated 08 / 09 / 2025, page 319 / 513 / 231 a 4- to 7-membered heterocyclic ring that is optionally substituted with one or more substituents selected from halo, hydroxy, cyano, amino, alkyl(1-4C) or alkoxy(1-4C); (ii) when it is a cycloalkyl(3-8C), 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl and 6- to 12-membered spiro-heterocyclyl, Q1 is optionally further substituted by one or more substituent groups selected independently from oxo, halo, cyano or by one or more groups of the formula: -Y3-Q3 where: Y3 is absent or selected from either -O-, -SO2-, -N(Ry3)-, C(O)-, -C(O)N(Ry3)-, -N(Ry3)C(O)-, -S(O)2N(Ry3)- or -N(Ry3)SO2-, wherein Ry3 is selected from either hydrogen or methyl; Q3 is selected from: hydrogen; an alkyl(1-4C) group that is optionally substituted with one or more substituents selected from halo, hydroxy, cyano, amino or alkoxy(1-4C); or a 4- to 7-membered heterocyclic ring that is optionally substituted with one or more substituents selected from halo, hydroxy, cyano, amino, alkyl(1-4C) or alkoxy(1-4C); (iii) when it is 5- to 6-membered phenyl or heteroaryl, Q1 is optionally further replaced by one or more substituent groups independently selected from halo, cyano or from one or more groups of the -Y3-Q3 formula defined above (60) Rx5 or Rx6 are selected from hydrogen, halo, cyano, nitro or a group of the formula: -L1-Y1-L2-Q1 Petition 870250080361, dated 08 / 09 / 2025, pages 320 / 513 / 231 in which: Li is absent or methylene; Yi is absent or -O-, -SO2-, -S(O)(=NRyi)-, -N(Ryi)-, C(O)N(Ryi)-, -N(Ryi)C(O)-, -S(O)2N(Ryi)- or -N(Ryi)SO2-, wherein Ryi and Ryia are selected from hydrogen or alkyl(i-2C); L2 is absent or methylene; and Qi is hydrogen, alkyl(i-4C), cycloalkyl(3-4C), phenyl, 5- to 6-membered heteroaryl, 4- to 7-membered heterocyclyl, 6- to i0-membered bicyclic heterocyclyl, 6- to i0-membered bridging heterocyclyl, and 6- to i2-membered spiroheterocyclyl, wherein: (i) when it is alkyl(i-4C), Qi is optionally further replaced by one or more substituent groups selected independently from halo, cyano or by one or more groups of the formula: -Y2-Q2 where: Y2 is absent or selected from either -O-, -SO2-, -N(Ry2)-, C(O)-, -C(O)N(Ry2)- or -N(Ry2)C(O)-, -S(O)2N(Ry2)- or -N(Ry2)SO2-, wherein Ry2 is selected from either hydrogen or methyl; Q2 is selected from: hydrogen; an alkyl(i-4C) optionally substituted with one or more halos; or a 4- to 7-membered heterocyclic ring; (ii) when it is a cycloalkyl(3-6C), 4- to 7-membered heterocyclylate, 6- to i0-membered bicyclic heterocyclylate, 6- to i0-membered bridging heterocyclylate and 6- to i2-membered spiro-heterocyclylate, Qi is optionally further substituted by one or more substituent groups independently selected from oxo, halo, cyano or by one or more groups of Petition 870250080361, dated 08 / 09 / 2025, page 321 / 513 / 231 formula: -Y3-Q3 where: Y3 is absent or selected from either -O-, -SO2-, -N(Ry3)-, C(O)-, -C(O)N(Ry3)-, -N(Ry3)C(O)-, -S(O)2N(Ry3)- or -N(Ry3)SO2-, wherein Ry3 is selected from either hydrogen or methyl; Q3 is selected from: hydrogen; an alkyl(1-4C) optionally substituted with one or more halos; or a 4- to 7-membered heterocyclic ring; (iii) when it is 5- to 6-membered phenyl or heteroaryl, Q1 is optionally further replaced by one or more substituent groups selected independently from halo, cyano or by one or more groups of the -Y3-Q3 formula defined above; (61) Rx5 or Rx6 are selected from hydrogen, halo, cyano, nitro or a group of the formula: -L1-Y1-L2-Q1 where: L1 is absent or methylene; Y1 is absent or -O-, -SO2-, -S(O)(=NRy1)-, -N(Ry1)-, C(O)N(Ry1)-, -N(Ry1)C(O)-, -S(O)2N(Ry1)- or -N(Ry1)SO2-, wherein Ry1 and Ry1a are selected from hydrogen or (1-2C) alkyl; L2 is absent or methylene; and Q1 is hydrogen, alkyl (1-4C), cycloalkyl (3-4C), phenyl, 5- to 6-membered heteroaryl, 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl, and 6- to 12-membered spiroheterocyclyl, wherein: Petition 870250080361, dated 08 / 09 / 2025, page 322 / 513 / 231 (i) when it is alkyl(1-4C), Qi is optionally further replaced by one or more substituent groups selected independently from halo, cyano or by one or more groups of the formula: -Y2-Q2 where: Y2 is absent or selected from either -O-, -SO2-, or -N(Ry2)-, wherein Ry2 is selected from either hydrogen or methyl; Q2 is selected from: hydrogen; an alkyl(1-4C) optionally substituted with one or more halos; or a 4- to 7-membered heterocyclic ring; (ii) when it is a cycloalkyl(3-6C), 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl and 6- to 12-membered spiro-heterocyclyl, Q1 is optionally further substituted by one or more substituent groups selected independently from oxo, halo, cyano or by one or more groups of the formula: -Y3-Q3 where: Y3 is absent or selected from either -O-, -SO2-, or -N(Ry3)-, wherein Ry3 is selected from either hydrogen or methyl; Q3 is selected from: hydrogen; an alkyl(1-4C) optionally substituted with one or more halos; or a 4- to 7-membered heterocyclic ring; (iii) when it is a 5- to 6-membered phenyl or heteroaryl group, Q1 is optionally further replaced by one or more substituent groups Petition 870250080361, dated 08 / 09 / 2025, page 323 / 513 / 231 selected independently from halo, cyan or by one or more groups of the -Y3-Q3 formula defined above; (62) Rx5 or Rx6 are selected from hydrogen, halo, cyano, nitro or a group of the formula: -L1-Y1-L2-Q1 where: L1 is missing; Y1 is absent or -O-, -SO2-, -S(O)(=NRy1)-, -N(Ry1)-, C(O)N(Ry1)-, -N(Ry1)C(O)-, -S(OhN(Ry1)- or -N(Ry1)SO2-, wherein Ry1 and Ry1a are selected from hydrogen or (1-2C) alkyl; L2 is absent or methylene; and Q1 is hydrogen, alkyl (1-4C), cycloalkyl (3-4C), phenyl, 5- to 6-membered heteroaryl, 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl, and 6- to 12-membered spiroheterocyclyl, wherein: (i) when it is alkyl(1-4C), Q1 is optionally further replaced by one or more substituent groups selected independently from halo, cyano or by one or more groups of the formula: -Y2-Q2 where: Y2 is missing or -O-; Q2 is selected from: hydrogen; an alkyl(1-4C) optionally substituted with one or more halos; or a 4- to 7-membered heterocyclic ring; (ii) when it is a cycloalkyl(3-6C), 4- to 7-membered heterocyclyla, 6- to 10-membered bicyclic heterocyclyla, bridge heterocyclyla Petition 870250080361, dated 08 / 09 / 2025, page 324 / 513 / 231 to 10 members and spiro-heterocycline from 6 to 12 members, Qi is optionally further replaced by one or more substituent groups selected independently from oxo, halo, cyan or by one or more groups of the formula: -Y3-Q3 where: Y3 is missing or -O-; Q3 is selected from among: hydrogen; an alkyl(1-4C) optionally substituted with one or more halos; or a 4- to 7-membered heterocyclic ring; (iii) when it is 5- to 6-membered phenyl or heteroaryl, Q1 is optionally further replaced by one or more substituent groups selected independently from halo, cyano or by one or more groups of the -Y3-Q3 formula defined above; (63) Rx7 is selected from hydrogen, fluorine, chlorine or methyl; (64) Rx7 is hydrogen; (65) X8 is N; (66) X8 is CH; (67) the integer c is 1 and the integer d is 0 or 1; (68) R100a and R100b are both R100 as defined here before; (69) R100a and R100b are both R100 as defined in paragraph (25) above; (70) R100a and R100b are both R100 as defined in paragraph (26) above; (71) R100a and R100b are both R100 as defined in paragraph (27) above; Petition 870250080361, dated 08 / 09 / 2025, page 325 / 513 / 231 (72) R100a and R100b are both R100 as defined in paragraph (28) above; (73) R100a and R100b are both R100 as defined in paragraph (29) above; (74) R100a and R100b are both R100 as defined in paragraph (30) above; (75) R100a and R100b are both R100 as defined in paragraph (31) above; (76) the integer e is 0 or 1; (77) Riooc is as defined in paragraph (23) above; (78) Riooc is as defined in paragraph (26) above; (79) Riooc is as defined in paragraph (27) above; (80) Riooc is as defined in paragraph (28) above; (81) Riooc is as defined in paragraph (29) above; (82) Riooc is as defined in paragraph (30) above; (83) Riooc is as defined in paragraph (31) above; (84) R2 and R3, when present, are selected, each one independently, from the group consisting of fluoro, oxo, alkyl(12C), alkoxy(1-2C), -CH2-C(O)-NH2, -CH2-C(O)-NHMe or -CH2-C(O)-NMe2; (85) R2 and R3, when present, are methyl, oxo or -CH2-C(O)- NMe2; (86) Rx4 is selected from hydrogen, fluorine, chlorine, bromine, methyl or a group of the formula: -YQ where: Y is -O-, -O-CH2-, -S-, -NH-, -CH2- or -CH2-CH2-; Q is selected from hydrogen, alkyl(1-4C), -C(O)-NH2, -C(O)-NHMe, -C(O)-NMe2, cycloalkyl(3-6C), phenyl, 5- or 6-membered heteroaryl, 4- to 7-membered heterocyclyl; Petition 870250080361, dated 08 / 09 / 2025, page 326 / 513 / 231 (87) Rx4 is selected from hydrogen, fluorine, chlorine, bromine or methyl; (88) Rx5 or Rx6 are selected from hydrogen, halo, cyano, nitro or a group of the formula: -L1-Y1-L2-Q1 where: L1 is absent or methylene; Y1 is absent or -O-, -SO2-, -S(O)(=NRy1)-, -N(Ry1)-, C(O)N(Ry1)-, -N(Ry1)C(O)-, -S(O)2N(Ry1)- or -N(Ry1)SO2-, wherein Ry1 and Ry1a are selected from hydrogen or (1-2C) alkyl; L2 is absent or alkylene(1-2C); and Q1 is hydrogen, alkyl (1-4C), cycloalkyl (3-4C), phenyl, 5- to 6-membered heteroaryl, 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl, and 6- to 12-membered spiroheterocyclyl, wherein: (i) when it is alkyl(1-4C), Q1 is optionally further replaced by one or more substituent groups selected independently from oxo, halo, cyano or by one or more groups of the formula: -Y2-Q2 where: Y2 is absent or selected from either -O-, -SO2-, -OC(O)-, N(Ry2)-, -C(O)N(Ry2)- or -N(Ry2)C(O)-, wherein Ry2 is selected from either hydrogen or methyl; Q2 is selected from: hydrogen; an alkyl(1-4C) optionally substituted with one or more halos; or a 4- to 7-membered heterocyclic ring; Petition 870250080361, dated 08 / 09 / 2025, page 327 / 513 / 231 (ii) when it is a cycloalkyl(3-6C), 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl and 6- to 12-membered spiro-heterocyclyl, Q1 is optionally further substituted by one or more substituent groups independently selected from oxo, halo, cyano or by one or more groups of the formula: -Y3-Q3 where: Y3 is absent or selected from either -O-, -SO2-, or -N(Ry3)-, wherein Ry3 is selected from either hydrogen or methyl; Q3 is selected from: hydrogen; an alkyl(1-4C) optionally substituted with one or more halos; or a 4- to 7-membered heterocyclic ring; (iii) when it is 5- to 6-membered phenyl or heteroaryl, Q1 is optionally further replaced by one or more substituent groups selected independently from halo, cyano or by one or more groups of the -Y3-Q3 formula defined above; (89) Rx5 or Rx6 are selected from hydrogen, halo, cyano, nitro or a group of the formula: -L1-Y1-L2-Q1 where: L1 is missing; Y1 is absent or -O-, -SO2-, -S(O)(=NRy1)-, -N(Ry1)-, C(O)N(Ry1)-, -N(Ry1)C(O)-, -S(O)2N(Ry1)- or -N(Ry1)SO2-, wherein Ry1 and RyU are selected from hydrogen or (1-2C) alkyl; L2 is absent or alkylene(1-2C); and Q1 is hydrogen, alkyl(1-4C), cycloalkyl(3-4C), phenyl, Petition 870250080361, dated 08 / 09 / 2025, page 328 / 513 / 231 heteroaryl with 5 to 6 members, heterocyclyl with 4 to 7 members, bicyclic heterocyclyl with 6 to 10 members, bridging heterocyclyl with 6 to 10 members and spiro-heterocyclyl with 6 to 12 members, wherein: (i) when it is alkyl(1-4C), Qi is optionally further replaced by one or more substituent groups selected independently from oxo, halo, cyano or by one or more groups of the formula: -Y2-Q2 where: Y2 is absent, -O-, -OC(O)-, -C(O)NH- or -C(O)NMe-; Q2 is selected from: hydrogen; an alkyl(1-4C) optionally substituted with one or more halos; or a 4- to 7-membered heterocyclic ring; (ii) when it is a cycloalkyl(3-6C), 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl and 6- to 12-membered spiro-heterocyclyl, Q1 is optionally further substituted by one or more substituent groups selected independently from oxo, halo, cyano or by one or more groups of the formula: -Y3-Q3 where: Y3 is missing or -O-; Q3 is selected from: hydrogen; an alkyl(1-4C) optionally substituted with one or more halos; or a 4- to 7-membered heterocyclic ring; Petition 870250080361, dated 08 / 09 / 2025, page 329 / 513 / 231 (iii) when it is phenyl or heteroaryl with 5 to 6 members, Qi is optionally further replaced by one or more substituent groups selected independently from halo, cyano or by one or more groups of the -Y3-Q3 formula defined above.

[0085] Properly, in compounds of formula I, ring A is as defined herein before or as defined in any of paragraphs (1) to (18) above. More properly, ring A is as defined in paragraphs (12) to (18) above. Most properly, ring A is as defined in paragraphs (15) or paragraph (16) above.

[0086] Properly, in compounds of formula I, R1 is as defined herein before or is as defined in either paragraph (19) to (24) above. More properly, R1 is as defined in paragraphs (21) to (23) above. Most properly, R1 is as defined in paragraph (22) or paragraph (23) above.

[0087] Properly, in compounds of formula I, R100 is as defined herein before or is as defined in either paragraphs (25) to (31) above. More properly, R100 is as defined in paragraphs (27) to (31) above. The most proper is R100 being as defined in paragraph (27) or paragraph (30) above.

[0088] Properly, in compounds of formula I, the integers aeb are as defined herein before or are as defined in either paragraph (32) to (34) above. More properly, the integers aeb are as defined in paragraph (32) or paragraph (33) above. Most properly, the integers aeb are as defined in paragraph (32) above.

[0089] Properly, in compounds of formula I, R2 and R3 are as defined herein before or are as defined in any of paragraphs (35) to (38), (84) or (85) above. More properly, R2 and R3 are as defined in paragraphs (36) to (38) or (85) above. The most suitable is R2 Petition 870250080361, dated 08 / 09 / 2025, page 330 / 513 / 231 and R3 being as defined in paragraph (36) or paragraph (37) above.

[0090] Properly, in compounds of formula I, X4, X5, X6 and X7 are as defined herein before or are as defined in any of paragraphs (39) to (54) above. More properly, X4, X5, X6 and X7 are as defined in paragraph (40) above. Most properly, X4, X5, X6 and X7 are as defined in paragraphs (41), (42), (49) or (50) above.

[0091] Properly, in compounds of formula I, Rx4 is as defined herein before or is as defined in any of paragraphs (55) to (58), (86) or (87) above. More properly, Rx4 is as defined in paragraphs (56) to (58) or (87) above. Most properly, Rx4 is as defined in paragraph (57) or paragraph (58) above.

[0092] Properly, in compounds of formula I, Rx5 is as defined herein before or is as defined in any of paragraphs (59) to (62), (88) or (89) above. More properly, Rx5 is as defined in paragraph (60) or (89) above. Most properly, Rx5 is as defined in paragraph (61) or paragraph (62) above.

[0093] Properly, in compounds of formula I, Rx6 is as defined herein before or is as defined in any of paragraphs (59) to (62), (88) or (89) above. More properly, Rx6 is as defined in paragraph (60) or (89) above. Most properly, Rx6 is as defined in paragraph (61) or paragraph (62) above.

[0094] Appropriately, at least one of Rx5 and Rx6 is not hydrogen. In one embodiment, when both Rx5 and Rx6 are present, Rx6 is not hydrogen. In another embodiment, when both Rx5 and Rx6 are present, Rx5 is not hydrogen. In one embodiment, when both Rx5 and Rx6 are present and Rx5 is hydrogen, Rx6 is not hydrogen. In one embodiment, when both Rx5 and Rx6 are present and Rx6 is hydrogen, Rx5 is not hydrogen.

[0095] In one embodiment, Rx5 and Rx6 are as defined herein before Petition 870250080361, dated 08 / 09 / 2025, page 331 / 513 / 231 on the condition that at least one of Rx5 and Rx6 is not hydrogen. In another embodiment, Rx5 and Rx6 are as defined in paragraph (59) above, on the condition that at least one of Rx5 and Rx6 is not hydrogen. In another embodiment, Rx5 and Rx6 are as defined in paragraph (60) above, on the condition that at least one of Rx5 and Rx6 is not hydrogen. In another embodiment, Rx5 and Rx6 are as defined in paragraph (61) above, on the condition that at least one of Rx5 and Rx6 is not hydrogen. In another embodiment, Rx5 and Rx6 are as defined in paragraph (62) above, on the condition that at least one of Rx5 and Rx6 is not hydrogen. In another embodiment, Rx6 is as defined in paragraph (59) above, provided that Rx6 is not hydrogen. In another embodiment, Rx6 is as defined in paragraph (60) above, provided that Rx6 is not hydrogen.In another embodiment, Rx6 is as defined in paragraph (61) above, provided that Rx6 is not hydrogen. In another embodiment, Rx6 is as defined in paragraph (62) above, provided that Rx6 is not hydrogen. In another embodiment, Rx5 and Rx6 are as defined in paragraph (88) above, provided that at least one of Rx5 and Rx6 is not hydrogen. In another embodiment, Rx5 and Rx6 are as defined in paragraph (89) above, provided that at least one of Rx5 and Rx6 is not hydrogen. In another embodiment, Rx6 is as defined in paragraph (88) above, provided that Rx6 is not hydrogen. In another embodiment, Rx6 is as defined in paragraph (89) above, provided that Rx6 is not hydrogen.

[0096] Properly, in compounds of formula I, Rx7 is as defined herein before or is as defined in either paragraph (63) or (64) above. More properly, Rx7 is as defined in paragraph (63) above. The most proper is Rx7 being as defined in paragraph (64) above.

[0097] Properly, in compounds of formula I, X8 is as defined herein before or is as defined in either paragraph (65) or Petition 870250080361, dated 08 / 09 / 2025, page 332 / 513 / 231 (66). More accurately, Xs is as defined in paragraph (65) above.

[0098] Properly, in compounds of formula I, the integers ced are as defined herein before or are as defined in paragraph (67) above.

[0099] Properly, in compounds of formula I, the integer and is as defined herein before or are as defined in paragraph (76) above.

[00100] Properly, in compounds of formula I, Riooa and Rioob are as defined herein before or are as defined in either paragraphs (68) to (75) above. More properly, Ri00a and Ri00b are as defined in paragraph (70). Most properly, Ri00a and Ri00b are as defined in paragraph (72) or paragraph (73) above.

[00101] Properly, in compounds of formula I, Ri00c is as defined herein before in paragraph (23) above.

[00102] In a particular group of compounds of formula I, the compounds, or a pharmaceutically acceptable salt thereof, have one of the structural formulas Ia to Iam shown below: Ia ·I· Ic Petition 870250080361, dated 08 / 09 / 2025, page 333 / 513 / 231 Ie If ig Oh ij Thousand· Im Io Petition 870250080361, dated 08 / 09 / 2025, page 334 / 513 / 231 IP IQ iy Petition 870250080361, dated 08 / 09 / 2025, page 335 / 513 / 231 Iz Hili lae lag Petition 870250080361, dated 08 / 09 / 2025, page 336 / 513 / 231 in which: the ring A, Ri, Rioo, R2, R3, the integer a, the integer b, X4, X5, Xó, X7, Rx4, Rx5, Rx6, Rx7, Xs, the integer c, Riooa, the integer d, Rioob, the integer ee Riooc have any of the meanings defined herein before or are as defined in any of paragraphs (1) to (89) above. [ooio3] In a particular group of compounds of the invention, the compounds have the structural formula Ia shown above. [oo1o4] In a particular group of compounds of the invention, the compounds have the structural formula Ib shown above. [oo1o5] In a particular group of compounds of the invention, the compounds have the structural formula Ic shown above. [oo1o6] In a particular group of compounds of the invention, the compounds have the structural formula Id shown above. [oo1o7] In a particular group of compounds of the invention, the compounds have the structural formula Ie shown above. [oo1o8] In a particular group of compounds of the invention, the compounds have the structural formula If shown above. [oo1o9] In a particular group of compounds of the invention, the Petition 870250080361, dated 09 / 08 / 2025, p. 337 / 513 / 231 compounds have the structural formula Ig shown above.

[00110] In a particular group of compounds of the invention, the compounds have the structural formula Ih shown above.

[00111] In a particular group of compounds of the invention, the compounds have the structural formula Ii shown above.

[00112] In a particular group of compounds of the invention, the compounds have the structural formula Ij shown above.

[00113] In a particular group of compounds of the invention, the compounds have the structural formula Ik shown above.

[00114] In a particular group of compounds of the invention, the compounds have the structural formula Im shown above.

[00115] In a particular group of compounds of the invention, the compounds have the structural formula In shown above.

[00116] In a particular group of compounds of the invention, the compounds have the structural formula Io shown above.

[00117] In a particular group of compounds of the invention, the compounds have the structural formula Ip shown above.

[00118] In a particular group of compounds of the invention, the compounds have the structural formula Iq shown above.

[00119] In a particular group of compounds of the invention, the compounds have the structural formula Ir shown above.

[00120] In a particular group of compounds of the invention, the compounds have the structural formula shown above.

[00121] In a particular group of compounds of the invention, the compounds have the structural formula It shown above.

[00122] In a particular group of compounds of the invention, the compounds have the structural formula Iu shown above.

[00123] In a particular group of compounds of the invention, the compounds have the structural formula Iv shown above. Petition 870250080361, dated 09 / 08 / 2025, p. 338 / 513 / 231

[00124] In a particular group of compounds of the invention, the compounds have the structural formula Iw shown above.

[00125] In a particular group of compounds of the invention, the compounds have the structural formula Ix shown above.

[00126] In a particular group of compounds of the invention, the compounds have the structural formula Iy shown above.

[00127] In a particular group of compounds of the invention, the compounds have the structural formula Iz shown above.

[00128] In a particular group of compounds of the invention, the compounds have the structural formula Iaa shown above.

[00129] In a particular group of compounds of the invention, the compounds have the structural formula Iab shown above.

[00130] In a particular group of compounds of the invention, the compounds have the structural formula Iac shown above.

[00131] In a particular group of compounds of the invention, the compounds have the structural formula Iad shown above.

[00132] In a particular group of compounds of the invention, the compounds have the structural formula Iae shown above.

[00133] In a particular group of compounds of the invention, the compounds have the structural formula Iaf shown above.

[00134] In a particular group of compounds of the invention, the compounds have the structural formula Iag shown above.

[00135] In a particular group of compounds of the invention, the compounds have the structural formula Iah shown above.

[00136] In a particular group of compounds of the invention, the compounds have the structural formula Iai shown above.

[00137] In a particular group of compounds of the invention, the compounds have the structural formula Iaj shown above.

[00138] In a particular group of compounds of the invention, the Petition 870250080361, dated 09 / 08 / 2025, p. 339 / 513 / 231 compounds have the structural formula lal shown above.

[00139] In a particular group of compounds of the invention, the compounds have the structural formula shown above.

[00140] In a particular group of compounds of the invention, the compounds have the structural formula shown above.

[00141] A particular group of compounds has any of the formulas Ia to Iam above, wherein, and when present, each of the rings A, R1, R100, R2, R3, the integer a, the integer b, X4, X5, Xg, X7, Rx4, Rx5, Rx6, Rx7, X8, R100a and R100b has the following definitions: ring A is as defined in paragraph (1) above; R1 is as defined in paragraph (19) above; R100 is as defined in paragraph (25) above; R2 is as defined in paragraph (35) above; R3 is as defined in paragraph (35) above; the integer a is as defined in paragraph (32) above; the integer b is as defined in paragraph (32) above; X4 is as defined in paragraph (39) above; X5 is as defined in paragraph (39) above; X6 is as defined in paragraph (39) above; X7 is as defined in paragraph (39) above; Rx4 is as defined in paragraph (55) above; Rx5 is as defined in paragraph (59) above; Rx6 is as defined in paragraph (59) above; Rx7 is as defined in paragraph (63) above; X8 is as defined in paragraph (65) above; the integer c is as defined in paragraph (67) above; the integer d is as defined in paragraph (67) above; R100a is as defined in paragraph (69) above; R100b is as defined in paragraph (69) above; Petition 870250080361, dated 08 / 09 / 2025, page 340 / 513 / 231 the integer number and is as defined in paragraph (76) above; Riooc is as defined in paragraph (78) above.

[00142] A particular group of compounds has any of the formulas Ia to Iam above, wherein, and when present, each of the rings A, R1, R100, R2, R3, the integer a, the integer b, X4, X5, Xg, X7, Rx4, Rx5, Rx6, Rx7, X8, R100a and R100b has the following definitions: ring A is as defined in paragraph (3) above; R1 is as defined in paragraph (18) above; R100 is as defined in paragraph (26) above; R2 is as defined in paragraph (36) above; R3 is as defined in paragraph (36) above; the integer a is as defined in paragraph (32) above; the integer b is as defined in paragraph (32) above; X4 is as defined in paragraph (39) above; X5 is as defined in paragraph (39) above; X6 is as defined in paragraph (39) above; X7 is as defined in paragraph (39) above; Rx4 is as defined in paragraph (56) above; Rx5 is as defined in paragraph (60) above; Rx6 is as defined in paragraph (60) above; Rx7 is as defined in paragraph (63) above; X8 is as defined in paragraph (65) above; the integer c is as defined in paragraph (67) above; the integer d is as defined in paragraph (67) above; R100a is as defined in paragraph (70) above; R100b is as defined in paragraph (70) above; the integer e is as defined in paragraph (76) above; R100c is as defined in paragraph (23) above.

[00143] A particular group of compounds has any of the Petition 870250080361, dated 08 / 09 / 2025, page 341 / 513 / 231 formulas Ia to Iam above, in which, and when present, each of the following within the ring A, Ri, R100, R2, R3, the integer a, the integer b, X4, X5, Xô, X7, Rx4, Rx5, Rx6, Rx7, X8, R100a and R100b has the following definitions: ring A is as defined in paragraph (12) above; Ri is as defined in paragraph (21) above; R100 is as defined in paragraph (27) above; R2 is as defined in paragraph (36) above; R3 is as defined in paragraph (36) above; the integer a is as defined in paragraph (32) above; the integer b is as defined in paragraph (32) above; X4 is as defined in paragraph (41) above; X5 is as defined in paragraph (41) above; X6 is as defined in paragraph (41) above; X7 is as defined in paragraph (41) above; Rx5 is as defined in paragraph (60) above; Rx6 is as defined in paragraph (60) above; X8 is as defined in paragraph (65) above; the integer c is as defined in paragraph (67) above; the integer d is as defined in paragraph (67) above; R100a is as defined in paragraph (72) above; R100b is as defined in paragraph (72) above; the integer and is as defined in paragraph (76) above; Riooc is as defined in paragraph (23) above.

[00144] A particular group of compounds has any of the formulas Ia to Iam above, wherein, and when present, each of the rings A, R100, R2, R3, the integer a, the integer b, X4, X5, X6, X7, Rx4, Rx5, Rx6, Rx7, X8, R100a and R100b has the following definitions: ring A is as defined in paragraph (15) above; R1 is as defined in paragraph (22) above; Petition 870250080361, dated 08 / 09 / 2025, pages 342 / 513 / 231 R100 is as defined in paragraph (30) above; R2 is as defined in paragraph (37) above; R3 is as defined in paragraph (37) above; the integer a is as defined in paragraph (32) above; the integer b is as defined in paragraph (32) above; X4 is as defined in paragraph (41) above; X5 is as defined in paragraph (41) above; X6 is as defined in paragraph (41) above; X7 is as defined in paragraph (41) above; Rx5 is as defined in paragraph (61) above; Rx6 is as defined in paragraph (61) above; X8 is as defined in paragraph (65) above; the integer c is as defined in paragraph (67) above; the integer d is as defined in paragraph (67) above; R100a is as defined in paragraph (73) above; R100b is as defined in paragraph (73) above; the integer and is as defined in paragraph (76) above; Riooc is as defined in paragraph (23) above.

[00145] A particular group of compounds has any of the formulas Ia to Iam above, wherein, and when present, each of the rings A, R1, R10O, R2, R3, the integer a, the integer b, X4, X5, Xo, X7, Rx4, Rx5, Rx6, Rx7, X8, R100a and R100b has the following definitions: ring A is as defined in paragraph (16) above; R1 is as defined in paragraph (23) above; R100 is as defined in paragraph (30) above; R2 is as defined in paragraph (37) above; R3 is as defined in paragraph (37) above; the integer a is as defined in paragraph (32) above; the integer b is as defined in paragraph (32) above; Petition 870250080361, dated 08 / 09 / 2025, page 343 / 513 / 231 X4 is as defined in paragraph (41) above; X5 is as defined in paragraph (41) above; X6 is as defined in paragraph (41) above; X7 is as defined in paragraph (41) above; Rx5 is as defined in paragraph (61) above; Rx6 is as defined in paragraph (61) above; X8 is as defined in paragraph (65) above; the integer c is as defined in paragraph (67) above; the integer d is as defined in paragraph (67) above; R100a is as defined in paragraph (73) above; R100b is as defined in paragraph (73) above; the integer and is as defined in paragraph (76) above; Riooc is as defined in paragraph (23) above.

[00146] A particular group of compounds has any of the formulas Ia to Iam above, wherein, and when present, each of the rings A, R1, R100, R2, R3, the integer a, the integer b, X4, X5, X6, X7, Rx4, Rx5, Rx6, Rx7, X8, R100a and R100b has the following definitions: ring A is as defined in paragraph (1) above; R1 is as defined in paragraph (19) above; R100 is as defined in paragraph (25) above; R2 is as defined in paragraph (84) above; R3 is as defined in paragraph (84) above; the integer a is as defined in paragraph (32) above; the integer b is as defined in paragraph (32) above; X4 is as defined in paragraph (39) above; X5 is as defined in paragraph (39) above; X6 is as defined in paragraph (39) above; X7 is as defined in paragraph (39) above; Rx4 is as defined in paragraph (86) above; Petition 870250080361, dated 08 / 09 / 2025, page 344 / 513 / 231 Rx5 is as defined in paragraph (88) above; Rx6 is as defined in paragraph (88) above; Rx7 is as defined in paragraph (63) above; X8 is as defined in paragraph (65) above; the integer c is as defined in paragraph (67) above; the integer d is as defined in paragraph (67) above; R100a is as defined in paragraph (69) above; R100b is as defined in paragraph (69) above; the integer and is as defined in paragraph (76) above; Riooc is as defined in paragraph (78) above.

[00147] A particular group of compounds has any of the formulas Ia to Iam above, wherein, and when present, each of the rings A, R1, R100, R2, R3, the integer a, the integer b, X4, X5, X6, X7, Rx4, Rx5, Rx6, Rx7, X8, Rx1a and Rx2b has the following definitions: ring A is as defined in paragraph (3) above; R1 is as defined in paragraph (19) above; R100 is as defined in paragraph (26) above; R2 is as defined in paragraph (85) above; R3 is as defined in paragraph (85) above; the integer a is as defined in paragraph (32) above; the integer b is as defined in paragraph (32) above; X4 is as defined in paragraph (39) above; X5 is as defined in paragraph (39) above; X6 is as defined in paragraph (39) above; X7 is as defined in paragraph (39) above; Rx4 is as defined in paragraph (87) above; Rx5 is as defined in paragraph (89) above; Rx6 is as defined in paragraph (89) above; Rx7 is as defined in paragraph (63) above; Petition 870250080361, dated 08 / 09 / 2025, page 345 / 513 / 231 Xs is as defined in paragraph (65) above; the integer c is as defined in paragraph (67) above; the integer d is as defined in paragraph (67) above; Riooa is as defined in paragraph (70) above; Rioob is as defined in paragraph (70) above; the integer and is as defined in paragraph (76) above; Riooc is as defined in paragraph (23) above.

[00148] A particular group of compounds has any of the formulas Ia to Iam above, wherein, and when present, each of the rings A, R1, R100, R2, R3, the integer a, the integer b, X4, X5, X6, X7, Rx4, Rx5, Rx6, Rx7, Xs, Rx1a and Rx2b has the following definitions: ring A is as defined in paragraph (12) above; R1 is as defined in paragraph (21) above; R100 is as defined in paragraph (27) above; R2 is as defined in paragraph (85) above; R3 is as defined in paragraph (85) above; the integer a is as defined in paragraph (32) above; the integer b is as defined in paragraph (32) above; X4 is as defined in paragraph (4i) above; X5 is as defined in paragraph (4i) above; X6 is as defined in paragraph (4i) above; X7 is as defined in paragraph (4i) above; Rx5 is as defined in paragraph (89) above; Rx6 is as defined in paragraph (89) above; X8 is as defined in paragraph (65) above; the integer c is as defined in paragraph (67) above; the integer d is as defined in paragraph (67) above; Riooa is as defined in paragraph (72) above; Rioob is as defined in paragraph (72) above; Petition 870250080361, dated 08 / 09 / 2025, page 346 / 513 / 231 the whole number and is as defined in paragraph (76) above; Riooc is as defined in paragraph (23) above.

[00149] A particular group of compounds has any of the formulas Ia to Iam above, wherein, and when present, each of the rings A, R1, R100, R2, R3, the integer a, the integer b, X4, X5, X6, X7, Rx4, Rx5, Rx6, Rx7, X8, R100a and R100b has the following definitions: ring A is as defined in paragraph (15) above; R1 is as defined in paragraph (22) above; R100 is as defined in paragraph (30) above; R2 is as defined in paragraph (85) above; R3 is as defined in paragraph (85) above; the integer a is as defined in paragraph (32) above; the integer b is as defined in paragraph (32) above; X4 is as defined in paragraph (41) above; X5 is as defined in paragraph (41) above; X6 is as defined in paragraph (41) above; X7 is as defined in paragraph (41) above; Rx5 is as defined in paragraph (89) above; Rx6 is as defined in paragraph (89) above; X8 is as defined in paragraph (65) above; the integer c is as defined in paragraph (67) above; the integer d is as defined in paragraph (67) above; R100a is as defined in paragraph (73) above; R100b is as defined in paragraph (73) above; the integer e is as defined in paragraph (76) above; R100c is as defined in paragraph (23) above.

[00150] A particular group of compounds has any of the formulas Ia to Iam above, wherein, and when present, each of the following is a ring: A, R1, R100, R2, R3, the integer a, the integer b, X4, X5, X6, X7, Rx4, Petition 870250080361, dated 08 / 09 / 2025, page 347 / 513 / 231 Rx5, Rx6, Rx7, X8, Riooa, and Rioob have the following definitions: ring A is as defined in paragraph (16) above; Ri is as defined in paragraph (23) above; R100 is as defined in paragraph (30) above; R2 is as defined in paragraph (85) above; R3 is as defined in paragraph (85) above; the integer a is as defined in paragraph (32) above; the integer b is as defined in paragraph (32) above; X4 is as defined in paragraph (41) above; X5 is as defined in paragraph (41) above; X6 is as defined in paragraph (41) above; X7 is as defined in paragraph (41) above; Rx5 is as defined in paragraph (89) above; Rx6 is as defined in paragraph (89) above; X8 is as defined in paragraph (65) above; the integer c is as defined in paragraph (67) above; the integer d is as defined in paragraph (67) above; R100a is as defined in paragraph (73) above; R100b is as defined in paragraph (73) above; the integer e is as defined in paragraph (76) above; R100c is as defined in paragraph (23) above.

[00151] A particular group of compounds has any of the formulas Ia to Iam above, wherein, and when present, each of R100, R2, R3, the integer a, the integer b, Rx4, Rx5, Rx6, Rx7, X8, R100a and R100b has any of the definitions described herein and each of the rings A, R1, X4, X5, X6 and X7 has the following definitions: ring A is as defined in paragraph (12) above; R1 is as defined in paragraph (21) above; X4 is selected from CH; Petition 870250080361, dated 08 / 09 / 2025, page 348 / 513 / 231 X5 is selected from N; X6 is selected from CRx6; and X7 is selected from either N or CH.

[00152] A particular group of compounds has any of the formulas Ia to Iam above, wherein, and when present, each of R100, R2, R3, the integer a, the integer b, Rx4, Rx5, Rx6, Rx7, X8, R100a and R100b has any of the definitions described herein and each of the rings A, Ri, X4, X5, X6 and X7 has the following definitions: ring A is as defined in paragraph (15) above; R1 is as defined in paragraph (22) above; X4 is selected from CH; X5 is selected from N; X6 is selected from CRx6; and X7 is selected from either N or CH.

[00153] A particular group of compounds has any of the formulas Ia to Iam above, wherein, and when present, each of R100, R2, R3, the integer a, the integer b, Rx4, Rx5, Rx6, Rx7, X8, R100a and R100b has any of the definitions described herein and each of the rings A, Ri, X4, X5, X6 and X7 has the following definitions: ring A is as defined in paragraph (17) above; R1 is as defined in paragraph (23) above; X4 is selected from CH; X5 is selected from N; X6 is selected from CRx6; and X7 is selected from either N or CH.

[00154] A particular group of compounds has any of the formulas Ia to Iam above, wherein, and when present, each of R100, R2, R3, the integer a, the integer b, Rx4, Rx5, Rx6, Rx7, X8, R100a and R100b has any of the definitions described herein and each of the ring Petition 870250080361, dated 08 / 09 / 2025, page 349 / 513 / 231 A, Ri, X4, X5, X6, and X7 have the following definitions: ring A is as defined in paragraph (18) above; Ri is as defined in paragraph (24) above; X4 is selected from CH; X5 is selected from N; X6 is selected from CRX6; and X7 is selected from either N or CH.

[00155] In a group of compounds of the invention, including compounds of formula I and any of the formulas Ia to Iam defined above, RX4 and Rx5, Rx5 and Rx6 or Rx6 and RX7 may be linked so that, together with the carbon atoms to which they are attached, they form a fused cycloalkyl(5-6C), phenyl, 5- or 6-membered heteroaryl or 5- or 6-membered heterocyclic ring, wherein each of them is optionally replaced by fluorine, chlorine, methyl or hydroxyl. In such compounds, all other variable groups may have any of the definitions set forth herein.

[00156] In such compounds, Rx4 and Rx5 are suitably linked so that, together with the carbon atoms to which they are attached, they form a 5- or 6-membered fused heteroaryl or 5- or 6-membered heterocyclic ring, wherein each of them is optionally replaced by fluorine, chlorine, methyl or hydroxyl.

[00157] In a particular group of compounds of the invention, including compounds of formula I and any of the formulas Ia to Iam defined above, Rx4 and Rx5 can be linked so that, together with the carbon atoms to which they are attached, they form a fused cycloalkyl(5-6C), phenyl, 5- or 6-membered heteroaryl or 5- or 6-membered heterocyclic ring, wherein each of these is optionally substituted with fluorine, chlorine, methyl or hydroxyl.

[00158] In such compounds, Rx4 and Rx5 are suitably linked so that, together with the carbon atoms to which they are attached, Petition 870250080361, dated 09 / 08 / 2025, p. 350 / 513 / 231 form a fused heteroaryl of 5 or 6 members or a heterocyclic ring of 5 or 6 members, in which each of them is optionally replaced by fluorine, chlorine, methyl or hydroxyl.

[00159] Particular compounds of the present invention include any of the compounds described in the examples section of this patent application, or a pharmaceutically acceptable salt thereof, and in particular, any of the following: N-(6-chloro-1,3-benzothiazol-2-yl)-4-(2-chloro-5-methoxy-4pyridyl)-6-methyl-pyridine-3-carboxamide; 2'-chloro-N-(6-methanesulfonyl-1,3-benzothiazol-2-yl)-5'methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-(6-cyano-1,3-benzothiazol-2-yl)-5'-methoxy-6-methyl[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-(6-iodo-1,3-benzothiazol-2-yl)-5'-methoxy-6-methyl[4,4'-bipyridine]-3-carboxamide; N-(6-bromo-1,3-benzothiazol-2-yl)-2'-chloro-5'-methoxy-6-methyl[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-{5-chloro-[1,3]thiazol[5,4-d]pyrimidin-2-yl}-5'methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N -{5-chloro-[1,3]thiazol[5,4-b]pyridin-2-yl}-5 '-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 3-(2-methoxyphenyl)-N-{[1,3]thiazol[5,4-d]pyrimidin-2-yl}pyridine-4-carboxamide; N-(6-bromo-1,3-benzothiazol-2-yl)-3-(2-methoxyphenyl)pyridine-4-carboxamide; 3-(2-methoxyphenyl)-N-{[1,3]thiazol[4,5-c]pyridin-2-yl}pyridine-4-carboxamide; 3-(2-methoxyphenyl)-N-{[1,3]thiazol[4,5-b]pyridin-2-yl}pyridine-4-carboxamide; Petition 870250080361, de 08 / 09 / 2025, pág. 351 / 513 / 231 3-(2-methoxyphenyl)-N-[5-(trifluoromethyl)-1,3-benzothiazol-2yl]pyridine-4-carboxamide; N-(5-chloro-1,3-benzothiazol-2-yl)-3-(2-methoxyphenyl)pyridine-4carboxamide; 3-(2-methoxyphenyl)-N-{[1,3]thiazol[5,4-b]pyridin-2-yl}pyridine-4-carboxamide; N-(1,3-benzothiazol-2-yl)-3-(2-methoxyphenyl)pyridine-4-carboxamide; N-(5-cyano-1,3-benzothiazol-2-yl)-3-(2-methoxyphenyl)pyridine-4-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(morpholin-4-yl)-1,3benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-(6-nitro-1,3-benzothiazol-2-yl)[4,4'-bipyridine]-3-carboxamide; 4-(2-chloro-5-methoxy-4-pyridyl)-N-[5-[(3R)-3-hydroxypyrrolidin-1-yl]thiazol[5,4-d]pyrimidin-2-yl]-6-methyl-pyridin-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(piperidin-1-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-[5-(4,4-difluoropiperidin-1-yl)-[1,3]thiazolo[5,4d]pyrimidin-2-yl]-5'-methoxy-6-methyl- [4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(morpholin-4-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-{5-[(3S)-3-hydroxypyrrolidin-1-yl]-[1,3]thiazolo[5,4d]pyrimidin-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(pyrrolidin-1-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-[5-(3,3-difluoropyrrolidin-1-yl)-[1,3]thiazol[5,4d]pyrimidin-2-yl]-5'-methoxy-6-metil- [4,4'-bipyridina]-3-carboxamide; 2'-chloro-N-{5-[(3R)-3-hydroxypyrrolidin-1-yl]-[1,3]thiazol[5,4 Petition 870250080361, de 08 / 09 / 2025, pág. 352 / 513 / 231 d]pyrimidin-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-[5-(1,1-dioxo-1À6-thiomorpholin-4-yl)-[1,3]thiazolo[5,4d]pyrimidin-2-yl]-5'-methoxy-6-methyl- [4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(4-methylpiperazin-1-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-(5-{2-oxa-6azaspiro[3.3]heptan-6-yl}-[1,3]thiazolo[5,4-d]pyrimidin-2-yl)-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-N-{5-[(2-methoxyethyl)amino]-[1,3]thiazolo[5,4d]pyrimidin-2-yl}-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N -[5-(3-hydroxyazetidin-1-yl)-[1,3]thiazolo[5,4d]pyrimidin-2-yl]-5'-methoxy-6-methyl- [4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-N-[5-(3-methoxypyrrolidin-1-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-[5-(4-hydroxypiperidin-1-yl)-[1,3]thiazolo[5,4d]pyrimidin-2-yl]-5'-methoxy-6-methyl- [4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-{5-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-[1,3]thiazol[5,4-d]pyrimidin-2-yl}-[4,4'bipyridine]-3-carboxamide; 2'-chloro-N-[5-(3-cyanopiperidin-1-yl)-[1,3]thiazol[5,4d]pyrimidin-2-yl]-5'-methoxy-6-methyl- [4,4'-bipyridine]-3-carboxamide; N-(6-amino-1,3-benzothiazol-2-yl)-4-(2-chloro-5-methoxy-4-pyridyl)-6-methyl-pyridine-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(2-oxopiperidin-1yl)-1,3-benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide; 4-(2-chloro-5-methoxy-4-pyridyl)-N-[5-(3,6-dihydro-2H-pyran-5yl)thiazol[5,4-b]pyridin-2-yl]-6-metil-pyridina-3-carboxamide; 4-(2-chloro-5-methoxy-4-pyridyl)-N-[6-(5-chloro-2-pyridyl)-1,3benzothiazol-2-yl]-6-methyl-pyridin-3-carboxamide; Petition 870250080361, de 08 / 09 / 2025, pág. 353 / 513 / 231 N-[6-(5-chloropyridin-2-yl)-1,3-benzothiazol-2yl]-3-(2-methoxyphenyl)pyridine-4-carboxamide; 2'-chloro-N-[6-(3-hydroxyoxolan-3-yl)-1,3-benzothiazol-2yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-(6-methanesulfonamido-1,3-benzothiazol-2yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-{[1,3]thiazol[5,4-d]pyrimidin-2yl}-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(methylsulfanyl)-1,3benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-{[1,3]thiazol[5,4-c]pyridin-2-yl}[4,4'-bipyridine]-3-carboxamide; N-[5-(4-acetylpiperazin-1-yl)-[1,3]thiazolo[5,4-d]pyrimidin-2-yl]2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N -{5-[(2-hydroxyethyl)amino] -[1,3 ]thiazol[5,4d]pyrimidin-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-N-[5-(3-methoxyazetidin-1-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-{5-[(4-hydroxycyclohexyl)amino]-[1,3]thiazol[5,4d]pyrimidin-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; rac-2'-chloro-N-(5-{[(1R,3S)-3-hydroxycyclopentyl]amino}[1,3]thiazol[5,4-d]pyrimidin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-{5-[(3R)-3-methylmorpholin-4-yl][1,3]thiazolo[5,4-d]pyrimidin-2-yl}-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-{5-[(3S)-3-methylmorpholin-4-yl][1,3]thiazolo[5,4-d]pyrimidin-2-yl}-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-{5-[(propan-2-yl)amino][1,3]thiazolo[5,4-d]pyrimidin-2-yl}-[4,4'-bipyridine]-3-carboxamide; Petition 870250080361, de 08 / 09 / 2025, pág. 354 / 513 / 231 2'-chloro-5'-methoxy-6-methyl-N-(5-{2-oxa-7-azaspiro[3,5]nonan7-yl}-[1,3]thiazol[5,4-d]pyrimidin-2-yl)-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-(5-{3,8-diazabiciclo[3.2.1]octan-3-yl}[1,3]thiazol[5,4-d]pyrimidin-2-yl)-5'-methoxy-6-metil-[4,4'-bipyridina]-3carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(piperazin-1-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(2-oxopyrrolidin-1-yl)-1,3benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(3-oxomorpholin-4-yl)-1,3benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(3-methyl-2-oxoimidazolidin1-yl)-1,3-benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(2-oxo-1,3-oxazolidin-3-yl)1,3-benzothiazol-2-yl]-[4,4' -bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(2-oxoimidazolidin-1-yl)-1,3benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(2-oxopiperidin-1-yl)[1,3]thiazol [4,5-c]pyridin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-{[1,3]thiazol[4,5-c]pyridin-2-yl}[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-{6-chloro-[1,3]thiazol[5,4-c]pyridin-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-{6-chloro-[1,3]thiazol[4,5-c]pyridin-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(morpholin-4-yl)[1,3]thiazol [4,5-c]pyridin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N -[6-(dimethylsulfamoyl)-1,3-benzothiazol-2-yl] -5'methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; Petition 870250080361, de 08 / 09 / 2025, pág. 355 / 513 / 231 2'-chloro-5'-methoxy-6-methyl-N-[6-(morpholin-4-yl)[1,3]thiazol [4,5-b]pyridin-2-yl]-[4,4' -bipyridine]-3-carboxamide; 2'-chloro-N-[6-(4-hydroxypiperidin-1-yl)-[1,3]thiazol[4,5c]pyridin-2-yl]-5'-methoxy-6-methyl-[4,4' -bipyridine]-3-carboxamide; N-(1,3-benzothiazol-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(2-oxopiperidin-1-yl)[1,3]thiazol [4,5-b]pyridin-2-yl]-[4,4' -bipyridine]-3-carboxamide; 2'-chloro-N-[6-(4-hydroxypiperidin-1-yl)-[1,3]thiazol[4,5b]pyridin-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(morpholin-4-yl)[1,3]thiazolo[5,4-b]pyridin-2-yl]-[4,4' -bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(2-oxopiperidin-1-yl)[1,3]thiazolo[5,4-b]pyridin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-[5-(4-hydroxypiperidin-1-yl)-[1,3]thiazolo[5,4b]pyridin-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-N-{5-methoxy-[1,3]thiazol[5,4-d]pyrimidin-2yl}-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-(5-{2-oxa-6-azaspiro[3.4]octan6-yl}-[1,3]thiazolo[5,4-d]pyrimidin-2-yl)-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N -{5-[(2-hydroxy-2-methylpropyl)amino][1,3]thiazol[5,4-d]pyrimidin-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-{5-[(2-methylpropyl)amino][1,3]thiazolo[5,4-d]pyrimidin-2-yl}-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-[5-(cyclobutylamino)-[1,3]thiazol[5,4-d]pyrimidin-2yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-N-[5-(4-methoxypiperidin-1-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-6-methyl-[4,4'-bipyridine]-3-carboxamide; Petition 870250080361, de 08 / 09 / 2025, pág. 356 / 513 / 231 2'-chloro-N-(5-{6-hydroxy-2-azaspiro[3.3]heptan-2-yl}[1,3]thiazolo[5,4-d]pyrimidin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-(5-{6-oxa-2-azaspiro[3.4]octan2-yl}-[1,3]thiazolo[5,4-d]pyrimidin-2-yl)-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N -{6-[imino(methyl)oxo-λ6-sulfanyl]-1,3-benzothiazol-2yl}-5'-methoxy-6-methyl-[4,4'-bipyridine] -3-carboxamide; 2'-chloro-N-[6-(1,1 -dioxo-1 λ6,2-thiazolidin-2-yl)-1,3benzothiazol-2-yl]-5'-methoxy-6-methyl-[4,4' -bipyridine]-3-carboxamide; 2'-chloro-N -{6-[(4R)-4-hydroxy-2-oxopiperidin-1-yl]-1,3benzothiazol-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(4-methyl-2-oxopiperazin-1-yl)1,3-benzothiazol-2-yl]-[4,4' -bipyridine]-3-carboxamide; 2'-chloro-N-[5-(3,6-dihydro-2H-pyran-4-yl)-[1,3]thiazolo[5,4d]pyrimidin-2-yl]-5'-methoxy-6-methyl- [4,4'-bipyridine]-3-carboxamide; N-[5-(4-hydroxypiperidin-1-yl)-[1,3]thiazolo[5,4-d]pyrimidin-2-yl]5'-methoxy-6-methyl-2'-(trifluoromethyl)-[4,4'-bipyridine]-3-carboxamide; N-[5-(4-hydroxypiperidin-1-yl)-[1,3]thiazolo[5,4-d]pyrimidin-2-yl]5'-methoxy-6-methyl-2'-(trifluoromethyl)-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(trifluoromethyl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-{5-methyl-[1,3]thiazol[5,4d]pyrimidin-2-yl}-[4,4'-bipyridine]-3-carboxamide; 5'-methoxy-2',6-dimethyl-N-[5-(morpholin-4-yl)-[1,3]thiazolo[5,4d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-fluoro-5'-methoxy-6-methyl-N-[5-(morpholin-4-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(2-oxopiperidin-1-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide; Petition 870250080361, de 08 / 09 / 2025, pág. 357 / 513 / 231 2'-chloro-N-(5-{[(2R)-2-hydroxypropyl]amino}-[1,3]thiazolo[5,4-d]pyrimidin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-(5-{[(2S)-2-hydroxypropyl]amino}-[1,3]thiazol[5,4-d]pyrimidin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-N-[5-(3-methoxy-3-methylazetidin-1yl)-[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-6-methyl-[4,4'-bipyridine]-3-carboxamide; N-(4-bromo-1,3-benzothiazol-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-{4-[2-(dimethylcarbamoyl)ethyl]-1,3-benzothiazol-2yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-[5-(cyanomethoxy)-1,3-benzothiazol-2-yl]-5'methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-{5-[difluoro(methylcarbamoyl)methoxy]-1,3-benzothiazol-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; N-(5-bromo-1,3-benzothiazol-2yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-{5-[(dimethylcarbamoyl)difluoromethoxy]-1,3-benzothiazol-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(methylcarbamoyl)-1,3-benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-N-(5-methoxy-1,3-benzothiazol-2yl)-6-methyl- [4,4' -bipyridine] -3-carboxamide; 2'-chloro-5'-methoxy-N-{5-[(2-methoxyethyl)carbamoyl]-1,3-benzothiazol-2-yl}-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-{7-[(dimethylcarbamoyl)methoxy]-[1,3]thiazol[5,4-d]pyrimidin-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; N-{5-[(1-acetylpiperidin-4-yl)methoxy]-1,3-benzothiazol-2yl}-2'-chloro-5'-methoxy-6-methyl- [4,4' -bipyridine] -3-carboxamide; 2'-chloro-N-{5-[(dimethylcarbamoyl)methoxy]-1,3-benzothiazol-2-one} Petition 870250080361, de 08 / 09 / 2025, pág. 358 / 513 / 231 il}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-{5-[2-(morpholin-4-yl)ethoxy]-1,3-benzothiazol-2-yl}-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(propan-2-yloxy)-1,3-benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-{5-[(1,1-dioxo-1-Z6-thietan-3 yl)methoxy]-1,3-benzothiazol-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-(5-ethoxy-1,3-benzothiazol-2yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-{5-[2-(trifluoromethoxy)ethoxy]-1,3-benzothiazol-2-yl}-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-N-[6-(3-methoxyazetidin-1yl)-[1,3]thiazolo[4,5-c]pyridin-2-yl]-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-{6-[(2-hydroxy-2-methylpropyl)amino]-[1,3]thiazol[4,5 -c]pyridin-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-N-[6-(3-methoxy-3-methylazetidin-1yl)-[1,3]thiazolo[4,5-c]pyridin-2-yl]-6-methyl-[4,4'-bipyridine]-3-carboxamide; 6-[(dimethylcarbamoyl)metil]-5'-methoxy-N-{[1,3]thiazol[5,4d]pyrimidin-2-yl}-2' -(trifluorometil)- [4,4'-bipyridina]-3-carboxamide; N-[5-(4-hydroxypiperidin-1-yl)-[1,3]thiazolo[5,4-d]pyrimidin-2yl]-5'-methoxy-2',6-dimethyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(2-oxopiperidin-1yl)-[1,3]thiazolo[5,4-b]pyridin-2-yl]-[4,4'-bipyridine]-3-carboxamide; acid 5-[(2-{2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-amido}-[1,3]thiazolo[4,5-c ]pyridin-6-yl)amino]pentanoic acid; acid 5-[(2-{2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-amido}-[1,3]thiazol[5,4-b Petition 870250080361, de 08 / 09 / 2025, pág. 359 / 513 / 231 ]pyridin-5-yl)amino]pentanoic; 2'-chloro-5'-methoxy-6-methyl-N-{5-[(2H-1,2,3,4-tetrazol-5-yl)methoxy]-1,3-benzothiazol-2-yl}-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-(5-hydroxy-1,3-benzothiazol-2yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; acetate 2-[(2-{2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-amido}-1,3-benzothiazol-5-yl)oxy]ethyl; 2'-chloro-N-[5-(2-hydroxyethoxy)-1,3-benzothiazol-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2' -chloro-5' -methoxy-1 -methyl-6-oxo- 1,6-dihydro-[3,4' -bipyridine] -4-carboxilato de 5-(4-hydroxypiperidin-1-yl)-[1,3]thiazol [5,4-d]pyrimidin-2-yl; 2'-chloro-N-[7-(cyanomethoxy)-[1,3]thiazol[5,4-d]pyrimidin-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; N-[7-(carbamoylmethoxy)-[1,3]thiazolo[5,4-d]pyrimidin-2yl]-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(morpholin-3yl)-1,3-benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-[5-(4-hydroxypiperidin-1yl)-7-methyl-[1,3]thiazol[5,4-d]pyrimidin-2-yl]-5'-methoxy-6-methyl- [4,4' -bipyridine] -3-carboxamide; 2'-chloro-N-[5-(2-hydroxy-2-methylpropoxy)-[1,3]thiazol[5,4-d]pyri midin-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide, or a pharmaceutically acceptable salt thereof.

[00160] Although the present invention may relate to any particular compound or group of compounds defined herein by way of optional, preferred or suitable characteristics or otherwise in terms of specific embodiments, the present invention may also relate to any particular compound or group of compounds that excludes Petition 870250080361, dated 09 / 08 / 2025, p. 360 / 513 / 231 specifically the so-called optional, preferred or suitable features or specific modalities.

[00161] Appropriately, the present invention excludes any individual compounds that do not possess the biological activity defined herein. Salts and solvates

[00162] The compounds (including end products and intermediates) described herein may be purified and used alone or may be isolated in the form of a salt, suitably pharmaceutically acceptable salts. It should be understood that the terms “salt(s)” and “salt form(s)”, used alone or in conjunction with another term or terms, encompass all inorganic and organic salts, including industrially acceptable salts as defined herein, and pharmaceutically acceptable salts as defined herein, unless otherwise specified. In this descriptive report, industrially acceptable salts are salts that are generally suitable for manufacture and / or processing (including purification) as well as for shipment and storage, but may not be salts that are typically administered for clinical or therapeutic use.Industrially acceptable salts can be prepared on a laboratory scale, i.e., milligrams or less, or on a larger scale, i.e., up to and including kilograms or more.

[00163] Pharmaceutically acceptable salts, in this descriptive report, are salts that are generally chemically and / or physically compatible with the other ingredients comprised in a formulation and / or are generally physiologically compatible with the recipient thereof. Pharmaceutically acceptable salts may be prepared on a laboratory scale, i.e., milligram or less, or on a larger scale, i.e., up to and including kilogram or more. It should be understood that pharmaceutically acceptable salts are not limited to salts that are typically administered or approved by the FDA or an equivalent foreign regulatory body for Petition 870250080361, dated 08 / 09 / 2025, page 361 / 513 / 231 clinical or therapeutic use in humans. Anyone skilled in the art will quickly recognize that some salts are both industrially acceptable and pharmaceutically acceptable. It should be understood that all such salts, including mixed salt forms, are covered by the scope of the patent application.

[00164] In one embodiment, compounds of Formula I and subformulas thereof are isolated as pharmaceutically acceptable salts.

[00165] A suitable pharmaceutically acceptable salt of a compound of the invention is, for example, an acid addition salt of a compound of the invention that is sufficiently basic, for example, an acid addition salt with, for example, an inorganic or organic acid, for example, hydrochloric, hydrobromic, sulfuric, phosphoric, trifluoroacetic, formic, citric or maleic acid. Furthermore, a suitable pharmaceutically acceptable salt of a compound of the invention that is sufficiently acidic is an alkali metal salt, for example, a sodium or potassium salt, an alkaline earth metal salt, for example, a calcium or magnesium salt, an ammonium salt, or a salt with an organic base that provides a physiologically acceptable cation, for example, a salt with methylamine, dimethylamine, trimethylamine, piperidine, morpholine or tris-(2-hydroxyethyl)amine.

[00166] In general, the salts of the present patent application can be prepared in situ during the isolation and / or purification of a compound (including intermediates), or by separately reacting the compound (or intermediate) with a suitable organic or inorganic acid or base (as appropriate) and isolating the salt thus formed. The degree of ionization in the salt can vary from completely ionized to nearly non-ionized. In practice, the various salts can be precipitated (with or without the addition of one or more co-solvents and / or anti-solvents) and collected by filtration, or the salts can be recovered by evaporation of solvent(s). The salts of the present patent application Petition 870250080361, dated 08 / 09 / 2025, page 362 / 513 / 231 patent can be formed by means of a “salt exchange” or ion exchange / double displacement reaction, that is, a reaction in which one ion is replaced (in whole or in part) by another ion with the same charge. Those skilled in the art will recognize that salts can be prepared and / or isolated using a single method or a combination of methods.

[00167] Representative salts include, among others, acetate, aspartate, benzoate, besylate, bicarbonate / carbonate, bisulfate / sulfate, borate, cansilate, citrate, edisilate, esilate, formate, fumarate, gluceptate, gluconate, glucuronate, hexafluorophosphate, hybenzate, hydrochloride / chloride, hydrobromide / bromide, iodide / iodide, isethionate, lactate, malate, maleate, malonate, mesylate, methylsulfate, naphthylate, 2-napsylate, nicotinate, nitrate, orotate, oxalate, palmitate, pamoate, phosphate / hydrogen phosphate / dihydrogen phosphate, saccharate, stearate, succinate, tartrate, tosylate, trifluoroacetate and the like.Other examples of representative salts include alkali or alkaline earth metal cations such as, among others, sodium, lithium, potassium, calcium, magnesium and the like, as well as non-toxic ammonium, quaternary ammonium and amine cations including, among others, ammonium, tetramethylammonium, tetraethylammonium, lysine, arginine, benzathine, choline, tromethamine, diolamine, glycine, meglumine, olamine and the like.

[00168] Certain compounds of Formula I and subformulas thereof may exist in solvated forms as well as non-solvated forms, such as hydrated forms. It should be understood that the invention covers all such solvated forms possessing the biological activity described herein. Polymorphs

[00169] It should also be understood that certain compounds of Formula I and subformulas thereof may exhibit polymorphism and that the invention encompasses all such forms possessing the biological activity described herein. Petition 870250080361, dated 08 / 09 / 2025, page 363 / 513 / 231 described. N-oxides

[00170] Compounds of Formula I and subformulas thereof containing an amine function may also form N-oxides. The reference here to a compound of Formula I and subformulas thereof containing an amine function also includes N-oxides. When a compound contains multiple amine functions, one or more nitrogen atoms may be oxidized to form an N-oxide. Specific examples of N-oxides are the N-oxides of a tertiary amine or a nitrogen atom of a nitrogen-containing heterocycle. N-oxides may be formed by treating the corresponding amine with an oxidizing agent such as, among others, hydrogen peroxide or a peracid (e.g., a peroxycarboxylic acid), see, for example, Advanced Organic Chemistry, by Jerry March, 4th Edition, Wiley Interscience, pages. More particularly, N-oxides may be produced by the procedure of L.W. Deady (Syn. Comm.1977, 7, 509-514) in which the amine compound is reacted with m-chloroperoxybenzoic acid (mCPBA), for example, in a solvent such as, among others, dichloromethane. Tautomers

[00171] Compounds of Formula I and subformulas thereof may exist in several different tautomeric forms, and references to compounds of Formula I and subformulas thereof include all such forms. For the avoidance of doubt, when a compound may exist in one of several tautomeric forms and only one is specifically described or shown, all others are nonetheless encompassed by Formula I and subformulas thereof. Examples of tautomeric forms include the keto, enol, and enolate forms, as in, for example, the following tautomeric pairs: keto / enol (illustrated below), pyrimidone / hydroxypyrimidine, imine / enamine, amide / imino alcohol, amidine / amidine, nitroso / oxime, thioketone / enethiol, and Petition 870250080361, dated 09 / 08 / 2025, p. 364 / 513 / 231 nitro / aci-nitro. HZOχOH H'χQ-—9“CC — C=C' — c=cX / \ H+ / \ keto enol enolate Isomers

[00172] Compounds that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or in the arrangement of their atoms in space are called “isomers.” Isomers that differ in the arrangement of their atoms in space are called “stereoisomers.” Stereoisomers that are not mirror images of each other are called “diastereomers,” and those that are mirror images that cannot be superimposed on each other are called “enantiomers.” When a compound has an asymmetric center, for example, when it is linked to four different groups, a pair of enantiomers is possible. An enantiomer can be distinguished by its absolute configuration and is described by the Cahn and Prelog R and S sequencing rules, or by the way in which the molecule rotates the plane of polarized light and is designated dextrorotatory or levorotatory (i.e., (+) or (-) isomers, respectively).A chiral compound can exist as an individual enantiomer or as a mixture of them. A mixture containing equal proportions of the enantiomers is called a "racemic mixture".

[00173] Certain compounds of Formula I and subformulas thereof may have one or more asymmetric centers and, therefore, may exist in various stereoisomeric configurations. Consequently, such compounds may be synthesized and / or isolated as mixtures of enantiomers and / or as individual (pure) enantiomers and, in the case of two or more asymmetric centers, as single diastereomers and / or mixtures of diastereomers. It should be understood that this patent application includes all such enantiomers and diastereomers and mixtures thereof in all proportions. Petition 870250080361, dated 09 / 08 / 2025, p. 365 / 513 / 231 Isotopes

[00174] The compounds of the present invention are described herein using structural formulas that do not specifically mention the mass numbers or isotope ratios of the constituent atoms. Thus, the intention is that the present patent application includes compounds in which the constituent atoms are present in any proportion of isotope forms. For example, carbon atoms may be present in any proportion of 12C, 13C and 14C; hydrogen atoms may be present in any proportion of 1H, 2H and 3H; etc. Preferably, the constituent atoms in the compounds of the present invention are present in their natural proportions of isotope forms. Prodrugs and metabolites

[00175] The compounds of Formula I and subformulas thereof can be administered in the form of a prodrug that is broken down in the human or animal body to release a compound of the invention. A prodrug can be used to alter the physical and / or pharmacokinetic properties of a compound of the invention. A prodrug can be formed when the compound of the invention contains a suitable group or substituent to which a property-modifying group can be attached. Examples of prodrugs include in vivo cleavable ester derivatives that can be formed at a carboxy group or a hydroxy group in a compound of Formula I and in vivo cleavable amide derivatives that can be formed at a carboxy group or an amino group in a compound of Formula I and subformulas thereof.

[00176] Consequently, the present invention includes those compounds of Formula I and subformulas thereof as defined herein before when made available by organic synthesis and when made available within the human or animal body by means of cleavage of a prodrug thereof. Thus, the present invention includes those Petition 870250080361, dated 09 / 08 / 2025, p. 366 / 513 / 231 compounds of Formula I that are produced by means of organic synthesis and also compounds that are produced in the human or animal body by means of metabolism of a precursor compound, which is a compound of Formula I and subformulas thereof and may be a synthetically produced compound or a metabolically produced compound.

[00177] A suitable pharmaceutically acceptable prodrug of a compound of Formula I and subformulas thereof is one that, based on sound medical judgment, is suitable for administration to the human or animal body without undesirable pharmacological activities and without undue toxicity.

[00178] Several forms of prodrugs have been described, for example, in the following documents:- a) Methods in Enzymology, Vol. 42, p. 309-396, edited by K. Widder, et al. (Academic Press, 1985); b) Design of Pro-Drugs, edited by H. Bundgaard, (Elsevier, 1985); c) A Textbook of Drug Design and Development, edited by Krogsgaard-Larsen and H. Bundgaard, Chapter 5 “Design and Application of Pro-Drugs”, by H. Bundgaard p. 113-191 (1991); d) H. Bundgaard, Advanced Drug Delivery Reviews, 8, 1-38 (1992); e) H. Bundgaard, et al., Journal of Pharmaceutical Sciences, 77, 285 (1988); f) N. Kakeya, et al., Chem. Pharm. Bull., 32, 692 (1984); g) T. Higuchi and V. Stella, “Pro-Drugs as Novel Delivery Systems”, ACS Symposium Series, Volume 14; and h) E. Roche (editor), “Bioreversible Carriers in Drug Design”, Pergamon Press, 1987.

[00179] A pharmaceutically acceptable prodrug suitable for a Petition 870250080361, dated 09 / 08 / 2025, p. 367 / 513 / 231. A compound of Formula I and subformulas thereof that possesses a carboxy group is, for example, a cleavable ester thereof in vivo. An in vivo cleavable ester of a compound of Formula I containing a carboxy group is, for example, a pharmaceutically acceptable ester that is cleaved in the human or animal body to produce the parent acid.Pharmaceutically acceptable esters suitable for carboxy include C1-6 alkyl esters such as, but not limited to, methyl, ethyl and tert-butyl, C1-6 alkoxymethyl esters such as, but not limited to, methoxymethyl esters, C1-6 alkanoyloxymethyl esters such as, but not limited to, pivaloyloxymethyl esters, 3-phthalidyl esters, C38 cycloalkylcarbonyloxy-alkylC1-6 cycloalkyl esters such as, but not limited to, cyclopentylcarbonyloxymethyl and 1-cyclohexylcarbonyloxyethyl esters, 2-oxo-1,3-dioxolenylmethyl esters such as, but not limited to, 5-methyl-2-oxo-1,3-dioxolen-4-ylmethyl esters and C16 alkoxycarbonyloxy-alkylC1-6 alkoxy esters such as, but not limited to, methoxycarbonyloxymethyl and 1-methoxycarbonyloxyethyl esters.

[00180] A suitable pharmaceutically acceptable prodrug of a compound of Formula I and subformulas thereof having a hydroxy group is, for example, an ester or ether cleavable in vivo thereof. An ester or ether cleavable in vivo of a compound of Formula I and subformulas thereof containing a hydroxy group is, for example, a pharmaceutically acceptable ester or ether that is cleaved in the human or animal body to produce the parent hydroxy compound. Suitable pharmaceutically acceptable ester-forming groups for a hydroxy group include inorganic esters such as, but not limited to, phosphate esters (including phosphoramidine cyclic esters).Additional pharmaceutically acceptable ester-forming groups suitable for a hydroxyl group include C1-10 alkanoyl groups such as, but not limited to, acetyl, benzoyl, phenylacetyl and substituted benzoyl and phenylacetyl groups, C1-10 alkoxycarbonyl groups such as, but not limited to, ethoxycarbonyl, N,N-(C1-6)2-carbamoyl, 2-dialkylaminoacetyl and 2-carboxyacetyl groups. Examples of ring substituents include... Petition 870250080361, dated 08 / 09 / 2025, page 368 / 513 / 231 Phenylacetyl and benzoyl groups include aminomethyl, N-alkylaminomethyl, N,N-dialkylaminomethyl, morpholinomethyl, piperazin-1-ylmethyl and 4-(alkylC14a)piperazin-1-ylmethyl. Pharmaceutically acceptable ether-forming groups suitable for a hydroxyl group include α-acyloxyalkyl groups such as, among others, acetoxymethyl and pivaloyloxymethyl groups.

[00181] A suitable pharmaceutically acceptable prodrug of a compound of Formula I and subformulas thereof having a carboxy group is, for example, a cleavable amide thereof in vivo, for example, an amide formed with an amine such as, among others, ammonia, an alkylC14amine such as, among others, methylamine, an (alkylC1-4)2amine such as, among others, dimethylamine, N-ethyl-N-methylamine or diethylamine, an alkoxyC1-4alkylC2-4amine such as, among others, 2-methoxyethylamine, a phenyl-alkylC14amine such as, among others, benzylamine and amino acids such as, among others, glycine or an ester thereof.

[00182] A suitable pharmaceutically acceptable prodrug of a compound of Formula I and subformulas thereof having an amino group is, for example, a cleavable amide derivative thereof in vivo. Suitable pharmaceutically acceptable amides of an amino group include, for example, an amide formed with C1-10 alkanoyl groups such as, among others, an acetyl, benzoyl, phenylacetyl and substituted benzoyl and phenylacetyl group. Examples of ring substituents on phenylacetyl and benzoyl groups include aminomethyl, N-alkylaminomethyl, N,N-dialkylaminomethyl, morpholinomethyl, piperazin-1-ylmethyl and 4-(alkylC1-4)piperazin-1-ylmethyl.

[00183] The in vivo effects of a compound of Formula I and subformulas thereof may be exerted in part by one or more metabolites that are formed in the human or animal body after administration of a compound of Formula I and subformulas thereof. As stated herein before, the in vivo effects of a compound of Formula I and subformulas thereof may also be exerted by means of Petition 870250080361, dated 09 / 08 / 2025, p. 369 / 513 / 231 metabolism of a precursor compound (a prodrug). Pharmaceutical compositions

[00184] According to a further aspect of the invention, a pharmaceutical composition is provided comprising a compound of the invention as defined herein above, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in association with a pharmaceutically acceptable diluent or vehicle.

[00185] The compositions of the invention may be in a form suitable for oral use (for example, as tablets, lozenges, hard or soft capsules, aqueous or oily suspensions, emulsions, dispersible powders or granules, syrups or elixirs), for topical use (for example, as creams, ointments, gels or aqueous or oily solutions or suspensions), for administration by inhalation (for example, as a finely divided powder or a liquid aerosol), for administration by insufflation (for example, as a finely divided powder) or for parenteral administration (for example, as a sterile aqueous or oily solution for intravenous, subcutaneous, intramuscular, intraperitoneal or intramuscular administration or as a suppository for rectal administration).

[00186] The compositions of the invention can be obtained by conventional procedures, using conventional pharmaceutical excipients, as well known in the art. Thus, compositions intended for oral use may contain, for example, one or more coloring agents, sweeteners, flavorings and / or preservatives.

[00187] An effective amount of a compound of the present invention for use in therapy is an amount sufficient to treat or prevent a proliferative condition referred to herein, slow its progression and / or reduce the symptoms associated with the condition.

[00188] The amount of active ingredient that is combined with one or more excipients to produce a unique pharmaceutical form will vary. Petition 870250080361, dated 09 / 08 / 2025, p. 370 / 513 / 231 necessarily depending on the individual treated and the particular route of administration. For example, a formulation intended for oral administration to humans will generally contain, for example, 0.5 mg to 1.5 g of active agent (more appropriately 0.5 to 600 mg, for example, 1 to 200 mg) combined with an appropriate and convenient amount of excipients which may vary from about 5 to about 98 percent by weight of the total composition.

[00189] The dose size for therapeutic or prophylactic purposes of a compound of Formula I will naturally vary according to the nature and severity of the conditions, the age and sex of the animal or patient, and the route of administration, in accordance with well-known principles of medicine.

[00190] It should be noted that doses and administration schedules may vary with the type and severity of the condition to be relieved, and may include the administration of a single dose or multiple doses, i.e., 1x / day (once a day), 2x / day (twice a day), etc., over a particular period of time (days or hours). It should further be understood that, for any particular individual or patient, specific dosage schedules may need to be adjusted over time according to individual need and the professional judgment of the person administering or supervising the administration of the pharmaceutical compositions. For example, doses may be adjusted based on pharmacokinetic or pharmacodynamic parameters, which may include clinical effects such as toxic effects and / or laboratory values. Thus, the present patent application covers the gradual increase of the dose in the same patient, as determined by the person skilled in the art.Procedures and processes for determining the appropriate dosage(s) and administration schedule(s) are well known in the relevant art and will be readily ascertained by a person skilled in the art. Thus, any person skilled in the art will quickly appreciate and recognize that the dosage ranges presented here are exemplary. Petition 870250080361, dated 08 / 09 / 2025, page 371 / 513 / 231 only and which do not intend to limit the scope or practice of the pharmaceutical compositions described herein.

[00191] When using a compound of the invention for therapeutic or prophylactic purposes, it will generally be administered in such a way that a daily dose in the range of, for example, 0.1 mg / kg to 75 mg / kg of body weight is received, given in divided doses if necessary. In general, lower doses will be administered when a parenteral route is employed. Thus, for example, for intravenous or intraperitoneal administration, a dose in the range of, for example, 0.1 mg / kg to 30 mg / kg of body weight will generally be used. Similarly, for administration by inhalation, a dose in the range of, for example, 0.05 mg / kg to 25 mg / kg of body weight will be used.

[00192] For the compounds of the present invention, oral administration is particularly suitable. The compounds of the present invention can be formulated as a tablet, capsule, or solution for oral administration. Suitably, the compound of the present invention is formulated in a unit-dose form (e.g., a tablet or capsule) for oral administration. Typically, the unit-dose forms will contain about 0.5 mg to 1.5 g of a compound of this invention. Synthesis

[00193] The compounds of the present invention can be prepared by any suitable technique known in the field. Specific methods for forming the compounds of formula I defined herein are shown in the accompanying examples section.

[00194] In the description of the synthetic methods described herein and in any cited synthetic methods that are used to prepare the starting materials, it should be understood that all proposed reaction conditions, including choice of solvent, reaction atmosphere, reaction temperature, duration of the experiment, and workup procedures, may be Petition 870250080361, dated 09 / 08 / 2025, p. 372 / 513 / 231 selected by a technician in the subject matter.

[00195] It will be understood by a person skilled in the art of organic synthesis that the functionality present in various portions of the molecule must be compatible with the reagents and reaction conditions used.

[00196] It will be recognized that, during the synthesis of the compounds of the invention in the process defined herein, or during the synthesis of certain starting materials, it may be desirable to protect certain substituent groups to prevent their undesired reaction. A competent chemist will recognize when such protection is necessary and how such protecting groups can be put in place and later removed.

[00197] For examples of protecting groups, see one of the many general texts on the subject, for example, “Protective Groups in Organic Synthesis” by Theodora Green (publisher: John Wiley & Sons). Protecting groups can be removed by any convenient method described in the literature or known to a competent chemist to be appropriate for removing the protecting group in question, such methods being chosen so as to effect the removal of the protecting group with the least perturbation of groups elsewhere in the molecule.

[00198] Thus, if the reagents include, for example, groups such as amino, carboxy or hydroxy, it may be desirable to protect the group in some of the reactions mentioned here.

[00199] By way of example, a suitable protecting group for an amino or alkylamino group is, for example, an acyl group, for example, an alkanoyl group such as, among others, acetyl, an alkoxycarbonyl group, for example, a methoxycarbonyl, ethoxycarbonyl or t-butoxycarbonyl group, an arylmethoxycarbonyl group, for example, benzyloxycarbonyl, or an aroyl group, for example, benzoyl. The deprotection conditions for the above protecting groups necessarily vary with the choice of protecting group. Thus, for example, an acyl group, such as an alkanoyl group or Petition 870250080361, dated 08 / 09 / 2025, page 373 / 513 / 231. An alkoxycarbonyl group can be removed, for example, by hydrolysis with a suitable base such as, among others, an alkali metal hydroxide, for example, lithium or sodium hydroxide. Alternatively, an acyl group, such as a tert-butoxycarbonyl group, can be removed, for example, by treatment with a suitable acid, such as hydrochloric, sulfuric or phosphoric acid or trifluoroacetic acid, and an arylmethoxycarbonyl group, such as a benzyloxycarbonyl group, can be removed, for example, by hydrogenation with a catalyst, such as palladium held on carbon, or by treatment with a Lewis acid, for example, boron tris(trifluoroacetate). A suitable alternative protecting group to the primary amino group is, for example, a phthaloyl group which can be removed by treatment with an alkylamine, for example, dimethylaminopropylamine, or with hydrazine.

[00200] A suitable protecting group for a hydroxyl group is, for example, an acyl group, such as acetyl, an aroyl group, such as benzoyl, or an arylmethyl group, such as benzyl. The deprotection conditions for the above protecting groups will necessarily vary with the choice of protecting group. Thus, for example, an acyl group, such as an alkanoyl or aroyl group, can be removed, for example, by hydrolysis with a suitable base, such as an alkali metal hydroxide, such as lithium or sodium hydroxide or ammonia. Alternatively, an arylmethyl group, such as a benzyl group, can be removed, for example, by hydrogenation with a catalyst such as palladium held on carbon.

[00201] A suitable protecting group for a carboxy group is, for example, an esterifying group, for example, a methyl or ethyl group that can be removed, for example, by hydrolysis with a base such as sodium hydroxide, or, for example, a t-butyl group that can be removed, for example, by treatment with an acid, for example, an organic acid such as trifluoroacetic acid, or, for example, a benzyl group that Petition 870250080361, dated 08 / 09 / 2025, page 374 / 513 / 231 can be removed, for example, by hydrogenation with a catalyst such as carbon-supported palladium.

[00202] Resins can also be used as a protective group.

[00203] The methodology employed to synthesize a compound of formula (I) will vary depending on the nature of the ring A, Ri, R100, R2, R3, the integer a, the integer b, X4, X5, Xg, X7, Rx4, Rx5, Rx6, Rx7, Xs, R100a and Rioob and any substituent groups associated with them. Suitable processes for their preparation are further described in the attached examples section.

[00204] Once a compound of formula (I) has been synthesized by any of the processes defined herein, the process may then additionally comprise one or more of the following steps: (i) remove any residual protective groups present; (ii) convert the compound of formula (I) into another compound of formula (I); (iii) to form a pharmaceutically acceptable salt, hydrate or solvate of the compound of formula I; and / or (iv) to form a prodrug of the compound of formula I.

[00205] An example of (ii) above is when a compound of formula (I) is synthesized and then one or more of the ring groups A, Ri, R100, R2, R3, the integer a, the integer b, X4, X5, Xg, X7, Rx4, Rx5, Rx6, Rx7, Xs, Ri00a and Ri00b can be further reacted to change the nature of the group and provide an alternative compound of formula (I).

[00206] The resulting compounds of formula (I) can be isolated and purified using techniques well known in the field. Therapeutic uses and applications

[00207] The compounds of the present invention are potent inhibitors of Polθ. Data showing the inhibition of Polθ for the exemplified compounds are presented in the attached examples section. Petition 870250080361, dated 09 / 08 / 2025, p. 375 / 513 / 231

[00208] Consequently, compounds of formula I are useful for the treatment and / or prevention of diseases and conditions in which ΡοΙΘ is implicated, such as, for example, among others, the treatment and / or prevention of cancer and / or benign neoplasms.

[00209] In one aspect, the present invention provides a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, for use in therapy.

[00210] In another aspect, the present invention provides a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, for use in the treatment of a disease or condition in which the activity of ΡοΙΘ is implicated.

[00211] In another aspect, the present invention provides the use of a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for use in the treatment of a disease or condition in which the activity of ΡοΙΘ is implicated.

[00212] In another aspect, the present invention provides a method for treating a disease or condition in which the activity of ΡοΙΘ is involved, said method comprising administering to an individual in need thereof an effective amount of a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or of a pharmaceutical composition as defined herein.

[00213] In another aspect, the present invention provides a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, for use in the treatment of a disease or condition associated with abnormal activity of ΡοΙΘ. Petition 870250080361, dated 09 / 08 / 2025, p. 376 / 513 / 231

[00214] In another aspect, the present invention provides the use of a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for use in the treatment of a disease or condition associated with abnormal activity of P₂O₅.

[00215] In another aspect, the present invention provides a method for treating a disease or condition associated with abnormal activity of ΡοΙΘ, said method comprising administering to an individual in need thereof an effective amount of a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or of a pharmaceutical composition as defined herein.

[00216] In another aspect, the present invention provides a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, for use in the treatment of cancer or benign neoplasms.

[00217] In another aspect, the present invention provides the use of a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for use in the treatment of cancer or benign neoplasms.

[00218] In another aspect, the present invention provides a method for treating a cancer or a benign neoplasm, said method comprising administering to an individual in need thereof an effective amount of a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or of a pharmaceutical composition as defined herein.

[00219] A benign neoplasm may be, for example, hemangiomas, hepatocellular adenoma, cavernous hemangioma, focal nodular hyperplasia, acoustic neuromas, neurofibroma, bile duct adenoma, bile duct cystoma, fibroma, lipomas, leiomyomas, mesotheliomas, teratomas, Petition 870250080361, dated 08 / 09 / 2025, page 377 / 513 / 231 myxomas, regenerative nodular hyperplasia, trachomas, pyogenic granulomas, moles, uterine fibroids, thyroid adenomas, adrenocortical adenomas or pituitary adenomas. Benign neoplasia may be endometrial implants or an odontogenic keratocystic tumor.

[00220] In another aspect, the present invention provides a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein, for use in the treatment of cancer.

[00221] In another aspect, the present invention relates to the use of a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for use in the treatment of cancer.

[00222] In another aspect, the present invention provides a method for the treatment of cancer, said method comprising administering to an individual in need thereof an effective amount of a compound of Formula I, as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or of a pharmaceutical composition as defined herein.

[00223] The compounds of the present invention, or pharmaceutically acceptable salts thereof, can be used in the treatment of homologous recombination (HR) deficient cancer.

[00224] The compounds of the present invention, or pharmaceutically acceptable salts thereof, can be used in the treatment of a cancer that is distinguished by a reduction or absence of homologous recombinant (HR) components.

[00225] For this reason, the compounds of the present invention can be used in the treatment of cancers that are distinguished by a reaction or absence of one or more of the following genes: ATM, BARD1, PALB2, BRCA1 and BRCA2, the absence of one or more of the genes ATM, BARD1, PALB2, BRCA1 and Petition 870250080361, dated 08 / 09 / 2025, page 378 / 513 / 231 BRCA2 genes, or by a reduced function of the ATM, BARD1, PALB2, BRCA1 and BRCA2 proteins.

[00226] In a specific aspect of the invention, the compounds of the present invention, or pharmaceutically acceptable salts thereof, can be used in the treatment of a cancer that is distinguished by a reduction or absence of BRCA gene expression, by the absence of the BRCA gene, or by a reduced function of the BRCA protein.

[00227] In a further aspect, the present invention relates to compounds of the present invention, or pharmaceutically acceptable salts thereof, for use in the treatment of cancers that are resistant to treatment with PARP inhibitors.

[00228] The compounds of the present invention may be useful for the treatment of the adult population. The compounds of the present invention may also be useful for the treatment of the pediatric population.

[00229] As a consequence of their inhibition of P0I, the compounds of the present invention will be useful in providing a means of disabling the ability of cells to perform MMEJ. It is therefore anticipated that the compounds may prove useful in the treatment or prevention of proliferative disorders such as cancers. Furthermore, the compounds of the invention may be useful in the treatment of diseases in which there is a disorder associated with the accumulation of cells.

[00230] In one embodiment, the compounds of the present invention are suitably lethal in primary and secondary solid tumors deficient in BRCA1 and BRCA2, including breast, ovarian, prostate, and pancreatic tumors. In a further embodiment, the compounds of the present invention are suitably lethal in a variety of primary and secondary solid tumors that exhibit HRD through mechanisms other than BRCA deficiency, such as those with promoter hypermethylation. In these tumors in which no DSB repair pathway can be fully regulated Petition 870250080361, dated 09 / 08 / 2025, p. 379 / 513 / 231 negatively, the compound of the present invention can be supplied together with another DDR modulator, such as a PARP inhibitor, a DNA-PK inhibitor, an ATR inhibitor, an ATM inhibitor, a wee1 inhibitor or a CHK1 inhibitor.

[00231] In a further embodiment, the compounds of the present invention are suitably lethal in primary and secondary breast, ovarian, prostate and pancreatic tumors that retain BRCA1 deficiency, but which, after or not exposure to PARP inhibitor drugs, are resistant to treatment with PARP inhibitors.

[00232] In a further embodiment, the compounds of the present invention adequately increase the objective response rate (ORR), including the complete response rate (CRR), delay the onset of resistance to PARP inhibitors, increase time to relapse and disease-free survival (DFS), and increase overall survival (OS) of primary and secondary tumors (breast, ovary, prostate, and pancreas) with homologous recombination deficiency (HRD, deficient in BRCA1 / 2 and other HRD mechanisms) when provided with treatment programs with PARP inhibitors.

[00233] In a further embodiment, the compounds of the present invention adequately exhibit synthetic disease and / or synthetic lethality in a variety of tumors with loss of ATM activity (ATM- / -), particularly in the context of WT p53. Tumor types will include around 10% of all solid tumors, including gastric, lung, breast, and colorectal cancer (CRC), along with chronic lymphocytic leukemia (CLL). Co-administration with another DDR modifier such as a DNA-PK inhibitor, PARP inhibitor, or ATR inhibitor may further enhance such activity. P53 inhibitors will re-sensitize CLL to classical chemotherapy and chemo-immunotherapy from which drug resistance arose. Thus, according to a further embodiment, the Petition 870250080361, dated 08 / 09 / 2025, page 380 / 513 / 231: The pharmaceutical composition of the present invention further comprises a DNA-PK inhibitor, PARP inhibitor, or ATR inhibitor.

[00234] In a further embodiment, the compounds of the present invention adequately exhibit synthetic disease and / or synthetic lethality in a variety of tumors deficient in the non-homologous end-joining (NHEJ-D) double-strand break repair process. The tumor types will include approximately 2-10% of all solid tumors, including prostate, pancreas, cervix, breast, lung, bladder, and esophagus. Co-administration with another DDR modifier, such as a PARP inhibitor, ATM inhibitor, wee1 inhibitor, CHK inhibitor, or ATR inhibitor, may further enhance such activity. P0I inhibitors will further sensitize NHEJD-inducing cancer cells to double-strand break (DSB)-inducing chemotherapies and ionizing radiation-based therapies.Thus, according to a further embodiment, the pharmaceutical composition of the present invention additionally comprises a PARP inhibitor, ATM inhibitor, wee1 inhibitor, CHK inhibitor or ATR inhibitor.

[00235] In a further embodiment, the compounds of the present invention adequately reduce the stress response in DNA replication during chemotherapy of HR-proficient tumors such as ovarian tumor, non-small cell lung cancer (NSCLC), and breast cancer that overexpress PI. This will increase the objective response rate (ORR) to treatment and increase overall survival (OS). Such effects are particularly likely with cytarabine (Ara-C) and hydroxyurea, used in a wide variety of leukemias including chronic myeloid leukemia (CML), and the management of squamous cell carcinomas.

[00236] In a further embodiment, the compounds of the present invention suitably selectively sensitize solid tumors to radiotherapy, including EBRT and brachytherapy, with little or no Petition 870250080361, dated 09 / 08 / 2025, pp. 381 / 513 100 / 231 sensitization of normal tissues. In a context of fractional curative intent, this will increase locoregional control leading to greater survival. This will be particularly evident in the management of non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCC), rectal cancer, prostate cancer, and pancreatic cancer. In a further embodiment, the compounds of the present invention adequately demonstrate synthetic disease and / or synthetic lethality in tumors with deleted PTEN, such as prostate cancer, with or without co-administration with a PARP inhibitor. Furthermore, such tumors will exhibit differentiated sensitivity to radiotherapy due to both the deletion of PTEN and the P1I inhibitor that induced radiosensitivity.

[00237] In a further embodiment, the compounds of the present invention adequately suppress TLS polymerase activity, sensitizing primary and secondary solid tumors (e.g., breast, lung, ovarian, colorectal cancer) to drugs (e.g., cisplatin, mitomycin, and cyclophosphamide) as well as reducing the acquisition of drug-induced mutations implicated in tumor resistance, leading to prolonged remission and increased TTR.

[00238] In a further embodiment, the compounds of the present invention adequately resensitize BCR-ABL-positive CML that has developed resistance to imatinib, as well as other solid tumors with elevated levels of ligase Ilia, reduced levels of ligase IV and greater dependence on DSB repair by altEJ.

[00239] In a further embodiment, the compounds of the present invention adequately exhibit synthetic disease and / or synthetic lethality in primary and secondary ER breast cancers resistant to aromatase inhibitor, again exhibiting elevated levels of ligase I1a, reduced levels of ligase IV and greater dependence on DSB repair by altEJ.

[00240] According to a further aspect of the invention, it is provided Petition 870250080361, dated 09 / 08 / 2025, pp. 382 / 513 101 / 231 a compound of formula (I) as defined herein for use in the treatment of tumors that are distinguished by a homologous recombination deficiency (HRD).

[00241] It will be acknowledged that references in this descriptive report to “homologous recombination deficiency (HRD)” refer to any genetic variation that results in a deficiency or loss of function of the gene resulting from homologous recombination. Examples of such genetic variation include mutations (e.g., point mutations), substitutions, deletions, single nucleotide polymorphisms (SNPs), haplotypes, chromosomal abnormalities, copy number variation (CNV), epigenetics, DNA inversions, reduced expression, and localization errors.

[00242] In one embodiment, said homologous recombination genes are selected from among: ATM, ATR, BRCA1, BRCA2, BARD1, RAD51C, RAD50, CHEK1, CHEK2, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, PALB2 (FANCN), FANCP (BTBD12), ERCC4 (FANCQ), PTEN, CDK12, MRE11, NBS1, NBN, CLASPIN, BLM, WRN, SMARCA2, SMARCA4, LIG1, RPA1, RPA2, BRIP1 and PTEN.

[00243] It will be acknowledged that references in this descriptive report to “non-homologous end joining deficiency (NHEJD)” refer to any genetic variation that results in a deficiency or loss of function of the gene resulting from homologous recombination. Examples of such genetic variation include mutations (e.g., point mutations), substitutions, deletions, single nucleotide polymorphisms (SNPs), haplotypes, chromosomal abnormalities, copy number variation (CNV), epigenetics, DNA inversions, reduced expression, and localization errors.

[00244] In one embodiment, said non-homologous end-joining genes are selected from any one or more of: LIG4, NHEJ1, POLL, POLM, PRKDC, XRCC4, XRCC5, XRCC6, and DCLRE1C. Petition 870250080361, dated 08 / 09 / 2025, pages 383 / 513 102 / 231

[00245] According to a further aspect of the invention, a compound of formula (I) as defined herein is provided for use in the treatment of tumors that overexpress P0I.

[00246] According to a further aspect of the invention, a compound of formula (I) as defined herein is provided for use in the treatment of tumors exhibiting elevated levels of ligase Ilia, reduced levels of ligase IV and greater dependence on DSB repair by altEJ.

[00247] Cancer can be non-metastatic or metastatic and can be a solid tumor or a hematologic (“liquid”) cancer. Cancer can be selected, for example, from: (1) Carcinoma, including, for example, tumors derived from stratified squamous epithelium (squamous cell carcinomas) and tumors arising within organs or glands (adenocarcinomas). Examples include breast, colon, lung, prostate, ovarian, esophageal (including, but not limited to, adenocarcinoma and squamous cell carcinoma of the esophagus), basal-like breast carcinoma, basal cell carcinoma (a form of skin cancer), squamous cell carcinoma (various tissues), head and neck carcinoma (including, but not limited to, squamous cell carcinomas), stomach carcinoma (including, but not limited to, adenocarcinoma of the stomach, gastrointestinal stromal tumor), signet ring cell carcinoma, bladder carcinoma (including transitional cell carcinoma (a malignant neoplasm of the bladder)), bronchogenic carcinoma, colorectal carcinoma (including, but not limited to, colon carcinoma and rectal carcinoma), anal carcinoma, gastric carcinoma, lung carcinoma (including,among others, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), lung adenocarcinoma, squamous cell carcinoma, large cell lung cancer, bronchoalveolar carcinoma and mesothelioma), neuroendocrine tumors (including, among others, carcinoids of the gastrointestinal tract, breast and other organs), Petition 870250080361, dated 08 / 09 / 2025, pages 384 / 513 103 / 231 adrenocortical carcinoma, thyroid carcinoma, pancreatic carcinoma (including, but not limited to, pancreatic ductal adenocarcinoma, pancreatic adenocarcinoma, acinar cell carcinoma, intraductal papillary mucinous neoplasm with invasive carcinoma, cystic mucinous neoplasm with invasive carcinoma, islet cell carcinoma and neuroendocrine tumors), breast carcinoma (including, but not limited to, ductal carcinoma, lobular carcinoma, inflammatory breast cancer, clear cell carcinoma, mucinous carcinoma), ovarian carcinoma (including, but not limited to, epithelial ovarian carcinoma or epithelial-stromal surface tumor including serous tumor, endometrioid tumor and mucinous cystadenocarcinoma, sex cord stromal tumor), liver and bile duct carcinoma (including, but not limited to, hepatocellular carcinoma, cholangiocarcinoma and hemangioma), prostate carcinoma, adenocarcinoma, brain tumors (including, but not limited to, glioma,glioblastoma and medulloblastoma), germ cell tumors, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinoma, cystadenocarcinoma, kidney carcinoma (including, but not limited to, renal cell carcinoma, clear cell carcinoma and Wilms' tumor), medullary carcinoma, ductal carcinoma in situ or bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, cervical carcinoma, uterine carcinoma (including, but not limited to, endometrial adenocarcinoma, serous papillary carcinoma of the uterus, clear cell carcinoma of the uterus, uterine sarcomas and leiomyosarcomas, mixed Müllerian tumors), testicular carcinoma, osteogenic carcinoma, epithelial carcinoma, sarcomatoid carcinoma, nasopharyngeal carcinoma, laryngeal carcinoma; oral and oropharyngeal squamous cell carcinoma; (2) Sarcomas, including: osteosarcoma and osteogenic sarcoma (bone); chondrosarcoma (cartilage); leiomyosarcoma (smooth muscle); rhabdomyosarcoma (skeletal muscle); mesothelial sarcoma and mesothelioma Petition 870250080361, dated 08 / 09 / 2025, pages 385 / 513 104 / 231 (membranous lining of body cavities); fibrosarcoma (fibrous tissue); angiosarcoma and hemangioendothelioma (blood vessels); liposarcoma (adipose tissue); glioma and astrocytoma (neurogenic connective tissue found in the brain); myxosarcoma (primitive embryonic connective tissue); chordoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, Ewing's sarcoma, mixed mesenchymal and mesodermal tumor (mixed connective tissue types) and other soft tissue sarcomas; (3) Myeloma and multiple myeloma; (4) Hematopoietic tumors, including: myelogenous and granulocytic leukemia (malignancy of the myeloid and granulocytic white blood cell series); lymphocytic, lymphocytic and lymphoblastic leukemia (malignancy of the lymphoid and lymphocytic blood cell series); polycythemia vera and erythremia (malignancy of various blood cell products, but with a predominance of erythrocytes); myelofibrosis. (5) Lymphomas, including: Hodgkin's and non-Hodgkin's lymphoma; (6) Solid tumors of the nervous system including medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma, neuroblastoma and schwannoma; (7) Melanoma, uveal melanoma and retinoblastoma; and (8) Mixed types, including, for example, adenosquamous carcinoma, mixed mesodermal tumor, carcinosarcoma or teratocarcinoma.

[00248] Additional examples of cancers (and their benign equivalents) that can be treated (or inhibited) include, among others, tumors of epithelial origin (adenomas and carcinomas of various types including adenocarcinomas, squamous cell carcinomas, transitional cell carcinomas and other carcinomas) such as carcinomas of the bladder and urinary tract, breast, Petition 870250080361, dated 08 / 09 / 2025, pages 386 / 513 105 / 231 gastrointestinal tract (including the esophagus, stomach (gastric), duodenum, colon, rectum, and anus), liver (hepatocellular carcinoma), gallbladder and biliary system, exocrine pancreas, kidney, lung (e.g., adenocarcinomas, small cell lung carcinomas, non-small cell lung carcinomas, bronchoalveolar carcinomas, and mesotheliomas), head and neck (e.g., cancers of the tongue, oral cavity, larynx, pharynx, nasopharynx, tonsils, salivary glands, nasal cavity, and paranasal sinuses), ovary, fallopian tubes, peritoneum, vagina, vulva, penis, cervix, myometrium, endometrium, thyroid (e.g., follicular thyroid carcinoma), adrenal gland, prostate gland, skin and appendages (e.g., melanoma, basal cell carcinoma, squamous cell carcinoma, keratoacanthoma, nevus) dysplastic); hematological malignancies (i.e., leukemias, lymphomas) and pre-malignant hematological disorders and borderline malignancy disorders,including hematological malignancies and related conditions of the lymphoid lineage (e.g., acute lymphocytic leukemia [ALL], chronic lymphocytic leukemia [CLL], B-cell lymphomas such as diffuse large B-cell lymphoma [DLBCL], follicular lymphoma, Burkitt lymphoma, mantle cell lymphoma, MALT lymphoma, T-cell lymphomas and leukemias, natural killer cell [NK] lymphomas, Hodgkin lymphoma, hairy cell leukemia, monoclonal gammopathy of uncertain significance, plasmacytoma, multiple myeloma, and post-transplant lymphoproliferative disorders) and hematological malignancies and related conditions of the myeloid lineage (e.g., acute myeloid leukemia [AML], chronic myeloid leukemia [CML], chronic myelomonocytic leukemia [CMML], hypereosinophilic syndrome, myeloproliferative disorders such as polycythemia vera, essential thrombocythemia, and Primary myelofibrosis, myeloproliferative syndrome,Myelodysplastic syndrome and promyelocytic leukemia); tumors of mesenchymal origin, for example, sarcomas of soft tissue, bone or cartilage such as osteosarcomas, fibrosarcomas, chondrosarcomas, rhabdomyosarcomas, Petition 870250080361, dated 08 / 09 / 2025, pages 387 / 513 106 / 231 leiomyosarcomas, liposarcomas, angiosarcomas, Kaposi's sarcoma, Ewing's sarcoma, synovial sarcomas, epithelioid sarcomas, gastrointestinal stromal tumors, benign and malignant histiocytomas and dermatofibrosarcoma protuberans; tumors of the central or peripheral nervous system (e.g., astrocytomas, gliomas and glioblastomas, meningiomas, ependymomas, pineal tumors and schwannomas); endocrine tumors (e.g., pituitary tumors, adrenal tumors, islet cell tumors, parathyroid tumors, carcinoid tumors and medullary thyroid carcinoma); ocular and adnexal tumors (e.g., retinoblastoma); germ cell and trophoblastic tumors (e.g., teratomas, seminomas, dysgerminomas, hydatidiform moles and choriocarcinomas); and pediatric and embryonic tumors (e.g., medulloblastoma, neuroblastoma, Wilms' tumor, and primitive neuroectodermal tumors);or syndromes, congenital or not, that leave the patient susceptible to malignancy (for example, Xeroderma pigmentosum).

[00249] Specific examples of cancers that may be targeted by the compounds of the present invention include, but are not limited to, lymphoma, rhabdoid tumor, multiple myeloma, uterine cancer, gastric cancer, peripheral nervous system cancer, rhabdomyosarcoma, bone cancer, colorectal cancer, prostate cancer, mesothelioma, breast cancer, ovarian cancer, lung cancer, fibroblastic cancer, central nervous system cancer, urinary tract cancer, upper aerodigestive tract cancer, leukemia, kidney cancer, skin cancer, esophageal cancer, and pancreatic cancer. More particularly, the cancers may be one or more of the following: breast cancer, ovarian cancer, pancreatic cancer, prostate cancer, lung cancer, and / or colorectal cancer.

[00250] Many diseases are distinguished by persistent and dysregulated angiogenesis. Chronic proliferative diseases are frequently accompanied by deep angiogenesis, which may contribute to or maintain a Petition 870250080361, dated 08 / 09 / 2025, pages 388 / 513 107 / 231 inflammatory and / or proliferative state or leading to tissue destruction by invasive proliferation of blood vessels. Tumor growth and metastases have been shown to be dependent on angiogenesis. The compounds of the invention may therefore be useful in preventing or disrupting the onset of tumor angiogenesis. In particular, the compounds of the invention may be useful in the treatment of metastases and metastatic cancers.

[00251] Metastasis or metastatic disease is the spread of a disease from one organ or part to another non-adjacent organ or part. Cancers that can be treated by the compounds of the invention include primary tumors (i.e., cancer cells at the site of origin), locally invasive tumors (cancer cells that penetrate and infiltrate surrounding normal tissues in the local area), and metastatic (or secondary) tumors, i.e., tumors that have formed from malignant cells that have circulated through the bloodstream (hematogenous dissemination) or via the lymphatic system or through body cavities (trans-coelomic) to other sites and tissues in the body.

[00252] Specific cancers include hepatocellular carcinoma, melanoma, esophageal carcinoma, renal carcinoma, colon carcinoma, lung carcinoma (e.g., mesothelioma or pulmonary adenocarcinoma), breast cancer, bladder cancer, gastrointestinal cancer, ovarian cancer, and prostate cancer.

[00253] The compounds may also be useful in the treatment of tumor growth, pathogenesis, resistance to chemotherapy and radiotherapy by chemotherapy-sensitizing cells, and as an antimetastatic agent. Routes of administration

[00254] The compounds of the invention or pharmaceutical compositions comprising these compounds can be administered to an individual by any convenient route of administration, whether systemically / peripherally or topically (i.e., at the desired site of action).

[00255] Routes of administration include, among others, oral (by Petition 870250080361, dated 08 / 09 / 2025, pp. 389 / 513 108 / 231 example, by ingestion); buccal; sublingual; transdermal (e.g., by a patch, dressing, etc.); transmucosal (e.g., by a patch, dressing, etc.); intranasal (e.g., by nasal spray); ocular (e.g., by eye drops, eye ointment, etc.); pulmonary (e.g., by inhalation or insufflation therapy, e.g., via an aerosol, e.g., through the nose or mouth); rectal (e.g., by suppository or enema); vaginal (e.g., by pessary); parenteral, e.g., by injection, including subcutaneous, intradermal, intramuscular, intravenous, intra-arterial, intracardiac, intrathecal, intraspinal, intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subcuticular, intra-articular, subarachnoid and intrasternal; by implantation of a depot or reservoir pharmaceutical form, for example, subcutaneously or intramuscularly.

[00256] The compounds of the present invention are particularly suitable for oral administration. Combined therapies

[00257] The compounds of the invention, and salts, solvates thereof defined herein may be applied as a single therapy or may involve, in addition to the compound of the invention, one or more additional therapeutic agents, for example, an antitumor agent.

[00258] In the context of cancer treatment, in addition to the compound of the invention, therapy may further involve conventional surgery, radiotherapy and / or chemotherapy. Such chemotherapy may include one or more of the following categories of antitumor agents:- - other antiproliferative / antineoplastic drugs and combinations thereof, as used in medical oncology, such as, among others, alkylating agents (e.g., cisplatin, oxaliplatin, carboplatin, cyclophosphamide, nitrogen mustard, melphalan, chlorambucil, busulfan, temozolomide and nitrosoureas); antimetabolites (e.g., gemcitabine and antifolates such as, among others, fluoropyrimidines such as Petition 870250080361, dated 08 / 09 / 2025, pages 390 / 513 109 / 231 5-fluorouracil and tegafur, raltitrexed, methotrexate, cytosine arabinoside and hydroxyurea); antitumor antibiotics (e.g., anthracyclines such as adriamycin, bleomycin, doxorubicin, daunomycin, epirubicin, idarubicin, mitomycin-C, dactinomycin and mithramycin); antimitotic agents (e.g., vinca alkaloids such as vincristine, vinblastine, vindesine and vinorelbine and taxoids such as taxol and taxotero and polokinase inhibitors); and topoisomerase inhibitors (e.g., epipodophyllotoxins such as etoposide and teniposide, ansacrine, topotecan and camptothecin); - cytostatic agents such as, among others, antiestrogens (e.g., tamoxifen, fulvestrant, toremifene, raloxifene, droloxifene and iodoxifene), antiandrogens (e.g., bicalutamide, flutamide, nilutamide and cyproterone acetate), LHRH antagonists or LHRH agonists (e.g., goserelin, leuprorelin and buserelin), progestogens (e.g., megestrol acetate), aromatase inhibitors (e.g., anastrozole, letrozole, vorazol and exemestane) and 5α-reductase inhibitors such as, among others, finasteride; - anti-invasion agents [e.g., cSrc kinase family inhibitors such as 4-(6-chloro-2,3-methylenedioxyanilino)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-tetrahydropyran-4-yloxyquinazoline (AZD0530; International Patent Application WO 01 / 94341), N-(2-chloro-6-methylphenyl)-2{6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-ylamino}thiazol-5-carboxamide (dasatinib, BMS-354825; J. Med. Chem., 2004, 47, 6658-6661) and bosutinib (SKI-606), metalloproteinase inhibitors such as marimastat, plasminogen activator receptor function inhibitors urokinase or antibodies against heparanase]; - Growth factor function inhibitors: for example, such inhibitors include antibodies against growth factors and antibodies against growth factor receptors (e.g., the anti-erbB2 antibody trastuzumab [Herceptin™], the anti-EGFR antibody panitumumab, the Petition 870250080361, dated 08 / 09 / 2025, pages 391 / 513 110 / 231 anti-erbB1 cetuximab antibody [Erbitux, C225] and any antibodies against growth factors or growth factor receptors described by Stern et al. (Critical reviews in oncology / haematology, 2005, Vol. 54, pp. 11-29); These inhibitors also include tyrosine kinase inhibitors, for example, epidermal growth factor family inhibitors (e.g., EGFR family tyrosine kinase inhibitors such as, among others, N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine (gefitinib, ZD1839), N-(3-ethinylphenyl)6,7-bis(2-methoxyethoxy)quinazolin-4-amine (erlotinib, OSI-774) and 6-acrylamide-N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-quinazolin-4-amine (CI 1033), erbB2 tyrosine kinase inhibitors such as, among others, lapatinib); hepatocyte growth factor family inhibitors; insulin-like growth factor family inhibitors;Inhibitors of the platelet-derived growth factor family, such as imatinib and / or nilotinib (AMN107); serine / threonine kinase inhibitors (e.g., Ras / Raf signaling inhibitors such as farnesyltransferase inhibitors, e.g., sorafenib (BAY 43-9006), tipifarnib (R115777) and lonafarnib (SCH66336)), inhibitors of cell signaling via MEK and / or AKT kinases, c-kit inhibitors, abl kinase inhibitors, PI3 kinase inhibitors, Plt3 kinase inhibitors, CSF-1R kinase inhibitors, IGF (insulin-like growth factor) receptor kinase inhibitors; Aurora kinase inhibitors (e.g., AZD1152, PH739358, VX-680, MLN8054, R763, MP235, MP529, VX-528 and AX39459) and cyclin-dependent kinase inhibitors such as, among others, CDK2 and / or CDK4 inhibitors; - agents such as, among others, those that inhibit the effects of vascular endothelial growth factor, [for example, the anti-vascular endothelial cell growth factor antibody bevacizumab (Avastin™) and, for example, a VEGF tyrosine kinase receptor inhibitor such as, among others] Petition 870250080361, dated 08 / 09 / 2025, pages 392 / 513 111 / 231 others, vandetanib (ZD6474), vatalanib (PTK787), sunitinib (SU11248), axitinib (AG-013736), pazopanib (GW 786034) and 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline (AZD2171; Example 240 in WO 00 / 47212), compounds such as, among others, those described in International Patent Applications WO97 / 22596, WO 97 / 30035, WO 97 / 32856 and WO 98 / 13354 and compounds acting by other mechanisms (e.g., linomide, αγβ3 integrin function inhibitors and angiostatin)]; - agents that damage the vascular network such as, among others, Combretastatin A4 and compounds described in International Patent Applications WO 99 / 02166, WO 00 / 40529, WO 00 / 41669, WO 01 / 92224, WO 02 / 04434 and WO 02 / 08213; - an endothelin receptor antagonist, for example, zibotentan (ZD4054) or atrasentan; - antisense therapies, for example, those that target the targets listed above, such as, among others, ISIS 2503, an anti-ras antisense; - gene therapy approaches, including, for example, approaches to replace abnormal genes such as, among others, abnormal p53 or approaches for abnormal BRCA1 or BRCA2, GDEPT (gene-targeted enzyme prodrug therapy) such as, among others, those using cytosine deaminase, thymidine kinase or a bacterial nitroreductase enzyme, and approaches to increase patient tolerance to chemotherapy or radiotherapy such as gene therapy for multidrug resistance; and - Immunotherapy approaches, including, for example, ex vivo and in vivo approaches to increase the immunogenicity of the patient's tumor cells, such as, among others, transfection with cytokines like interleukin 2, interleukin 4, or granulocyte colony-stimulating factor. Petition 870250080361, dated 08 / 09 / 2025, pages 393 / 513 112 / 231 macrophages, approaches to decrease T cell anergy, approaches using transfected immune cells such as, among others, dendritic cells transfected with cytokines, approaches using tumor cell lines transfected with cytokines, and approaches using anti-idiotypic antibodies.

[00259] In a particular embodiment, the antiproliferative treatment defined herein may involve, in addition to the compound of the invention, conventional surgery or radiotherapy or chemotherapy.

[00260] In a further embodiment, the antiproliferative treatment defined herein may involve, in addition to the compound of the invention, standard chemotherapy for the cancer in question and / or therapy with inhibitors of DNA damage repair (e.g., inhibitors of PARP, ATM, ATR, WEE1, CHK1, USP1 and DNAPK).

[00261] In a further embodiment, the antiproliferative treatment defined herein may involve, in addition to the compound of the invention, therapy with a PARP inhibitor.

[00262] Such combined treatment can be performed by simultaneous, sequential or separate administration of the individual components of the treatment. Such combined products employ the compounds of this invention with the dosage range described herein above and the other pharmaceutically active agent within its approved dosage range.

[00263] According to this aspect of the invention, a combination is provided for use in the treatment of cancer (for example, cancer involving a solid tumor) comprising a compound of the invention, as defined herein above, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and another antitumor agent.

[00264] According to this aspect of the invention, a combination is provided for use in the treatment of a proliferative condition, such as, among others, cancer (for example, cancer involving a solid tumor), Petition 870250080361, dated 08 / 09 / 2025, pages 394 / 513 113 / 231 comprising a compound of the invention, as defined herein above, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and any of the antitumor agents listed above.

[00265] In a further aspect of the invention, a compound of the invention or a pharmaceutically acceptable salt, hydrate or solvate thereof is provided for use in the treatment of cancer in combination with another antitumor agent, optionally selected from one of those listed above.

[00266] Here, when the term “combination” is used, it should be understood that it refers to simultaneous, separate, or sequential administration. In one aspect of the invention, “combination” refers to simultaneous administration. In another aspect of the invention, “combination” refers to separate administration. In a further aspect of the invention, “combination” refers to sequential administration. When administration is sequential or separate, the waiting period for the administration of the second component should not be such as to lose the beneficial effect of the combination. In one embodiment, a combination refers to a combined product.

[00267] According to a further aspect of the invention, a pharmaceutical composition is provided comprising a compound of the invention, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in combination with an antitumor agent (optionally selected from one of those listed above), in association with a pharmaceutically acceptable diluent or vehicle. Biological activity

[00268] The biological assay described in the examples section (Biological assay 1) can be used to measure the pharmacological effects of the compounds of the present invention.

[00269] Although the pharmacological properties of the compounds of formula I vary with the structural alteration, as expected, the compounds of the invention have been shown to be active in the assays described in the Biological Assay. Petition 870250080361, dated 08 / 09 / 2025, pages 395 / 513 114 / 231 1. In general, the compounds of the invention demonstrate an IC50 of 5000 nM or less in the assay described in Biological Assay 1, with the preferred compounds of the invention demonstrating an IC50 of 100 nM or less and the most preferred compounds of the invention demonstrating an IC50 of 30 nM or less. Additional applications

[00270] The compounds of the present invention are also potentially useful agents for increasing the efficiency and robustness of CRISPR gene editing in vitro and in vivo.

[00271] In this regard, homologous recombination (HR) is paramount to ensure correct DNA modification (DNA insertion into the genome, base mutation, etc.). Consistent with the hypothesis that TMEJ competes with HR for access to DNA breaks (Mateos-Gomez PA, et al., (2017), Nat. Struct. Mol. Biol. (2017) 24(12):1116-1123), it has been shown that the loss of P0I leads to an increase in HR in CRISPR-induced breaks and improves the fidelity and frequency of genome modification (Mara K., et al., New Phyto. (2019); 222(3):1380-1391; Zelenski AN, et al., Nat. Commun., (2017); 8(1):66). Therefore, a PiI inhibitor can be used to increase the efficiency and robustness of CRISPR genome editing in vitro and potentially in vivo (Schimmel J. et al., Cell Rep. (2023) 42: 112019).

[00272] For this reason, it has been described that the loss of PαοΙΘ contributes to enhancing the effectiveness of CRISPR-mediated gene editing in document WO 2017 / 062754. Thus, the compounds of the invention will likely be useful for increasing the efficiency of CRISPR-based editing methodologies and / or CRISPR-based editing therapy. Furthermore, the inhibition of PαοΙΘ mediated by the compounds will likely reduce the frequency of random integration events and thus provide a pathway to improve any safety-related issues of CRISPR-mediated technology. Thus, according to a further aspect of the invention, the use of a compound of formula (I) is provided. Petition 870250080361, dated 08 / 09 / 2025, pages 396 / 513 115 / 231 as defined herein in a CRISPR-based editing methodology and / or CRISPR-based editing therapy, as the enhanced efficiency of the CRISPR-based editing methodology and / or CRISPR-based editing therapy.

[00273] For this reason, in a further aspect, the present invention provides the use of a compound of the invention (i.e., a compound of formula I or any subformulas thereof) or a salt, hydrate or solvate thereof, for gene editing by CRISPR in vitro or in vivo.

[00274] In another aspect, the present invention provides the use of a compound of the invention (i.e., a compound of formula I or any subformulas thereof), or a salt, hydrate or solvate thereof, to increase the efficiency of CRISPR gene editing in vitro or in vivo.

[00275] In another aspect, the present invention provides a compound of the invention (i.e., a compound of formula I or any subformulas thereof), or a salt, hydrate or solvate thereof, for use in CRISPR gene editing in vivo.

[00276] In another aspect, the present invention provides a compound of the invention (i.e., a compound of formula I or any subformulas thereof), or a salt, hydrate or solvate thereof, for use in increasing the efficiency of CRISPR gene editing in vivo. EXAMPLES - PART A

[00277] The invention will now be illustrated, but not limited to, by reference to the embodiments described in the following examples. The compounds are named using conventional IUPAC nomenclature, or as named by the chemical supplier.

[00278] The following synthetic procedures are provided for illustration of the methods used; for a given preparation or step, the precursor used may not necessarily be derived from the individual batch synthesized according to the step in the description provided. Petition 870250080361, dated 08 / 09 / 2025, pages 397 / 513 116 / 231 General

[00279] All solvents and chemical reagents were obtained from commercial sources and used without further purification or drying. NMR spectra were recorded on a Bruker Avance III HD 400 MHz, a Bruker NEO 400 MHz, a Bruker Avance III HD 500 MHz, a Bruker Avance NEO 500 MHz, or a Bruker Avance III HD 600 MHz spectrometer. Chemical shifts are quoted in ppm, using residual undeuterated solvent as the internal reference.

[00280] The LCMS spectra were recorded on a Waters Aquity UPLC, using: Method A - Waters UPLC® BEHTMC18 2.1 x 50 mm 1.7 column at 40°C, eluting with 0.1% formic acid in acetonitrile and 0.1% formic acid in water, using a gradient of 5-100% over 1.35 minutes at a rate of 0.9 mL / min; Method B - Phenomenex Kinetix-XB C18 column 2.1 x 100 mm, 1.7 gm at 40°C, eluting with 0.1% formic acid in acetonitrile and 0.1% formic acid in water, using a gradient of 5-100% over 5.8 minutes at a rate of 0.6 mL / min; Method C - Waters UPLC® BEHTMC18 2.1 x 50 mm 1.7 gm column at 55°C, eluting with 2 mM ammonium bicarbonate in water, buffered to pH 10 and acetonitrile using a gradient of 1-100% over 1.10 minutes at a rate of 1 mL / min; Method D - Waters UPLC® BEHTMC18 2.1 x 100 mm 1.7 g column at 55°C, eluting with 2 mM ammonium bicarbonate in water, buffered to pH 10 and acetonitrile using a 5-100% gradient over 5.30 minutes at a rate of 0.6 mL / min; Method E - Waters CSH C18 column 2.1 x 50 mm, 1.7 gm at 55°C, eluting with 0.035% TFA in acetonitrile and 0.05% TFA in water, using a gradient from 2% to 98% over 1.5 minutes at a rate of Petition 870250080361, dated 09 / 08 / 2025, pp. 398 / 513 117 / 231 0.8 mL / min; Method F - Waters CSH C18 column 2.1 x 50 mm, 1.7 gm at 55°C, eluting with 0.035% TFA in acetonitrile and 0.05% TFA in water, using a gradient from 2% to 98% over 2.4 minutes at a rate of 0.8 mL / min; Method G - Waters CSH C18 column 2.1 x 50 mm, 1.7 gm at 55°C, eluting with 0.02% formic acid in acetonitrile and 0.02% formic acid in water, using a gradient from 2% to 98% over 4.5 minutes at a rate of 1 mL / min; or Method H - Waters CSH C18 column 2.1 x 50 mm, 1.7 gm at 55°C, eluting with 0.02% formic acid in acetonitrile and 0.02% formic acid in water, using a gradient from 2% to 98% over 2.4 minutes at a rate of 0.8 mL / min.

[00281] Mass spectra were obtained with a Waters HPLCSQD, SQD2 or QDA detector using electrospray ionization in positive or negative mode. Purity by LCMS was assigned with AUC monitoring at 215, 254 or 280 nm.

[00282] Preparative HPLC was performed using: Method A - Waters Sunfire C18 column 30 mm x 100 mm, 5 μm at room temperature, using 30% 0.1% formic acid in acetonitrile and 70% 0.1% formic acid in water for 1.9 minutes, then a gradient of 30-95% 0.1% formic acid in acetonitrile for 9.6 minutes at a flow rate of 40 mL / min; Method B - Waters XBridge C18 column 30 mm x 100 mm, 5 μm at room temperature, using 30% acetonitrile and 70% ammonium hydroxide 0.2% in water for 2 minutes, then a gradient of 30-95% acetonitrile for 9.5 minutes at a flow rate of 40 mL / min; or Method C - Waters Sunfire™ C18 column (30 mm x 100 mm, 5 μm; temperature: ambient temperature), with injection volume Petition 870250080361, dated 09 / 08 / 2025, pp. 399 / 513 118 / 231 of 1500 pL at a flow rate of 40 mL / min of 10% B for 1.90 minutes, then a gradient of 10-95% B over 14.10 minutes and a hold of 2.0 minutes, where A = 0.1% formic acid in water and B = 0.1% formic acid in acetonitrile.

[00283] UV spectra were recorded at 215 nm using a Gilson detector. List of abbreviations

[00284] RT - Ambient temperature DTBPF - Di-tert-butylphosphinoferrocene THF - Tetrahydrofuran TCFH - Ν,Ν,Ν',Ν'tetramethylformamidinium chloro hexafluorophosphate DCM - Dichloromethane DIPEA - N,N-diisopropylethylamine DMF - Dimethylformamide DCE - Dichloroethane DPPF - Diphenylphosphinoferrocene Sat. - Saturated Equiv. - Equivalents SPhos - 2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl Pd2(dba)3 - Tris(dibenzylideneacetone)dipalladium(0) DPEPhos - (Oxidi-2,1-phenylene)bis(diphenylphosphine) THF - tetrahydrofuran DMAP - N,N-dimethylaminopyridine Rt - Retention time General scheme Petition 870250080361, dated 08 / 09 / 2025, pages 400 / 513 119 / 231 Procedure B Procedure D

[00285] In the scheme above, X100 is a halide; Ai is N or C-Me; A2 is N when Ai is C-Me, or A2 is CH when A is N; the groups RX5a and RX6a are different groups Rx5 and Rx6, respectively, formed by procedure D; the remaining groups are as defined here before. General procedure A for Suzuki coupling

[00286] A solution of the desired aryl halide (1 equiv.) in 1,4-dioxane / water (3:1, 0.2 mmol / mL) in a round-bottom flask fitted Petition 870250080361, dated 08 / 09 / 2025, pages 401 / 513 Using a magnetic stir bar, the corresponding boronic acid (1.5 equiv.), dipotassium carbonate (3.7 equiv.), and palladium catalyst (10 mol%) were added. The mixture was washed with nitrogen, fitted with a condenser, and stirred at 90°C for 18 hours. The reaction was cooled to room temperature, and the mixture was diluted with water and extracted with ethyl acetate. The organic extracts were combined, washed with brine, dried (Na2SO4), and concentrated under reduced pressure. The crude product was purified by automated chromatography with Biotage Isolera™ using an ethyl acetate-heptanes gradient to provide the desired biaryl products. Intermediate 1: 4-(2-chloro-5-methoxy-4-pyridyl)-6-methylpyridine-3-carboxylate

[00287] To a solution of methyl 4-chloro-6-methylpyridine-3-carboxylate (1.20 g, 6.47 mmol) in 1,4-dioxane (21 mL) and water (7 mL), in a 250 mL round-bottom flask fitted with a magnetic stir bar, (2-chloro-5-methoxy-4-pyridyl)boronic acid (1.60 g, 8.54 mmol), dipotassium carbonate (3.30 g, 23.9 mmol) and palladium dichloride DTBPF (360 mg, 0.55 mmol) were added. The mixture was washed with nitrogen, adjusted with a condenser, and stirred at 90°C for 18 hours. The reaction was cooled to room temperature and the mixture was diluted with water (50 mL) and extracted with ethyl acetate (3 x 50 mL). The organic extracts were combined, washed with brine, dried (Na2SO4), and the solvent was removed under reduced pressure. The crude product was purified by automated chromatography with Biotage Isolera™ (Sfar Duo, 100 g) using a 0-100% ethyl acetate gradient in heptane. The fractions that Petition 870250080361, dated 08 / 09 / 2025, pages 402 / 513 Samples 121 / 231 containing the product were evaporated under reduced pressure to give the title compound (5.03 g, 91% yield) as a whitish solid. 1H NMR (400 MHz, DMSO-de) δ 8.88 (s, 1H), 8.23 ​​(s, 1H), 7.50 (s, 1H), 7.38 (s, 1H), 3.78 (s, 3H), 3.68 (s, 3H), 2.58 (s, 3H). LCMS (method B); RT 2.58 minutes (100%), m / z 293.1 / 295.1 (M+H)+.

[00288] Intermediates 2 and 3 in Table 1 below were also synthesized using the general procedure A detailed above. Table 1 - Intermediates 2 and 3 synthesized using general procedure A Intermediate Yield Purity LCMS (%) LCMS RT (min.) m / z Method LCMS NMR 1H Intermediate 2 T | Methyl 3-(2-methoxyphenyl)pyridine-4-carboxylate 65 90 0.76 244.2 1H NMR (500 MHz, DMSO-de) δ 8.70 (d, J = 4.9 Hz, 1H), 8.59 (s, 1H), 7.64 (dd, J = 4.9; 0.8 Hz, 1H), 7.43 - 7.38 (m, 1H), 7.33 (dd, J = 7.4; 1.7 Hz, 1H), 7.09 - 7.04 (m, 2H), 3.66 (d, J = 2.7 Hz, 6H). Intermediate 3 । II ÃJ* 2'-chloro-5'-methoxy-6-methyl[4,4'-bipyridine]-3-carboxylate methyl 91 100 2.58 293.1 / 295.1 B NMR 1H (400 MHz, DMSO-de) δ 8.88 (s, 1H), 8.23 ​​(s, 1H), 7.50 (s, 1H), 7.38 (s, 1H), 3.78 (s, 3H), 3.68 (s, 3H), 2.58 (s, 3H). General procedure B for ester hydrolysis

[00289] To a solution of methyl ester (1 equiv.) in THF (0.2 mmol / mL), 1 M lithium hydroxide solution (2 equiv.) was added and the mixture was stirred for 18 hours. The mixture was acidified to pH 3 with 1 M aqueous HCl solution and extracted with ethyl acetate. The combined organic extracts were dried (Na2SO4) and the solvent removed under reduced pressure. The resulting solid was dried in a vacuum oven at 40°C overnight to provide the desired carboxylic acid. Petition 870250080361, dated 09 / 08 / 2025, pp. 403 / 513 122 / 231 Intermediate 4: acid Ad^chloro-SmethoxM-pyridylj-ó-m^ carboxylic

[00290] To a solution of methyl 4-(2-chloro-5-methoxy-4-pyridyl)-6-methylpyridine-3-carboxylate (5.03 g, 17.2 mmol) in THF (98 mL), 1 M lithium hydroxide solution (35 mL, 35.0 mmol) was added and the mixture was stirred for 18 hours. The mixture was acidified to pH 3 with 1 M aqueous HCl solution and extracted with ethyl acetate (3 x 25 mL). The combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure. The resulting solid was dried in a vacuum oven at 40°C overnight to give the title compound (3.30 g, 69% yield) as a white solid. 1H NMR (400 MHz, DMSO-de) δ 13.06 (s, 1H), 8.89 (s, 1H), 8.21 (s, 1H), 7.44 (s, 1H), 7.30 (s, 1H), 3.79 (s, 3H), 2.56 (s, 3H). LCMS (method B); RT 1.63 minutes (100%), m / z 279.1 / 281.1 (M+H)+.

[00291] Intermediates 5 and 6 in Table 2 below were also synthesized using the general procedure B detailed above. Table 2 - Intermediates 2 and 3 synthesized using general procedure A Intermediate Yield Purity LCMS (%) LCMS RT (min.) m / z Method LCMS 1H NMR Intermediate 5 3-(2-methoxyphenyl)pyridine-4-carboxylic acid W- 70 95 0.4 230.2 1H NMR (400 MHz, DMSO-de) δ 8.66 (d, J = 5.0 Hz, 1H), 8.53 (d, J = 0.7 Hz, 1H), 7.63 (dd, J = 5.0; 0.7 Hz, 1H), 7.40 - 7.36 (m, 1H), 7.28 (dd, J = 7.7; 1.7 Hz, 1H), 7.07 - 7.03 (m, 2H), 3.67 (s, 3H). Petition 870250080361, dated 09 / 08 / 2025, pp. 404 / 513 123 / 231 Intermediate 6 2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid ι II 69 100 1.63 279.1 / 281.1 B 1H NMR (400 MHz, DMSO-de) δ 13.06 (s, 1H), 8.89 (s, 1H), 8.21 (s, 1H), 7.44 (s, 1H), 7.30 (s, 1H), 3.79 (s, 3H), 2.56 (s, 3H) General Procedure C for Amide Coupling

[00292] To a solution of carboxylic acid (1.1 equiv.), amine (1 equiv.) and 1-methylimidazole (5.1 equiv.) in acetonitrile, a solution of TCFH (1.1 equiv.) in acetonitrile was added. The mixture was stirred for 18 hours at room temperature.

[00293] If it precipitated from the solution, the product was filtered, washed with diethyl ether, and dried in a vacuum oven at 40°C to provide the desired amide. If the product did not precipitate, the solution was diluted with ethyl acetate and washed with saturated aqueous NaHCO3 solution. The organic extracts were combined, dried (Na2SO4), and concentrated under reduced pressure. The crude product was purified by automatic chromatography with Biotage Isolera™ using a methanol-ethyl acetate gradient or preparative HPLC method A to provide the desired amide. Example 1 - N-(6-chloro-1,3-benzothiazol-2-yl)-4-(2-chloro-5-methoxy-4-pyridyl)o-methyl-pyridine-Bcarboxamide H3C OI CH l N H

[00294] To a solution of 4-(2-chloro-5-methoxy-4-pyridyl)-6-methylpyridine-3-carboxylic acid (50 mg, 0.18 mmol) in acetonitrile (1 mL), 6-chloro-1,3-benzothiazol-2-amine (36 mg, 0.20 mmol) and 1-methylimidazole (73 μL, 0.91 mmol) were added and washed with nitrogen. To the above solution, TCFH (53 mg, 0.20 mmol) in acetonitrile (1 mL) was added and the reaction mixture was stirred at room temperature for 18 hours. The product Petition 870250080361, dated 08 / 09 / 2025, pages 405 / 513 124 / 231 precipitated from the reaction mixture and was filtered. The filtered cake was washed sequentially with acetonitrile and diethyl ether, then dried in a vacuum oven at 40°C for 3 hours to give the title compound (53 mg, 66% yield) as a colorless powder. 1H NMR (500 MHz, DMSO-de) δ 13.04 (s, 1H), 8.85 (s, 1H), 8.16 (s, 1H), 8.13 (d, J = 2.2 Hz, 1H), 7.77 (d, J = 8.6 Hz, 1H), 7.58 (s, 1H), 7.50 - 7.44 (m, 2H), 3.59 (s, 3H), 2.60 (s, 3H). LCMS (method B); RT 3.60 minutes (99%), m / z 445.0 / 446.9 (M+H)+

[00295] Examples 2 to 18 in Table 3 below were also synthesized using the general procedure C detailed above. Table 3 - Examples 2 to 18 synthesized using the general procedure C Example Yield Purity LCMS (%) LCMS RT (min.) m / z LCMS Method 1H NMR Example 2 2'-chloro-N-(6methanesulfonyl-1,3benzothiazol-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3carboxamide „ XX 1 JL IMT 12 100 2.73 489.2 / 491.2 B 1H NMR (500 MHz, DMSO-de) δ 13.26 (s, 1H), 8.87 (s, 1H), 8.65 (s, 1H), 8.16 (s, 1H), 7.99 7.95 (m, 2H), 7.60 (s, 1H), 7.48 (s, 1H), 3.58 (s, 3H), 3.25 (s, 3H), 2.61 (s, 3H). Example 3 2'-chloro-N-(6-cyano-1,3benzothiazol-2-yl)-5'-methoxy6-methyl-[4,4'-bipyridine]-3carboxamide M. XT 15 100 3.1 436.2 / 438.2 B 1H NMR (500 MHz, DMSO-de) δ 13.28 (s, 1H), 8.87 (s, 1H), 8.58 (s, 1H), 8.16 (s, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.86 (dd, J = 8.5; 1.8 Hz, 1H), 7.60 (s, 1H), 7.48 (s, 1H), 3.58 (s, 3H), 2.61 (s, 3H). Petition 870250080361, dated 08 / 09 / 2025, pages 406 / 513 125 / 231 Exemplo 4 2’-cloro-N-(6-iodo-1,3benzotiazol-2-il)-5’-metoxi6-metil-[4,4’-bipiridina]-3carboxamida ! 72 100 3,79 535,1 / 537,1 B RMN 1H (500 MHz, DMSO-de) δ 13,02 (s, 1H), 8,85 (s, 1H), 8,39 (d, J = 1,8 Hz, 1H), 8,16 (s, 1H), 7,74 (dd, J = 8,4; 1,8 Hz, 1H), 7,59 - 7,55 (m, 2H), 7,46 (s, 1H), 3,59 (s, 3H), 2,60 (s, 3H). Exemplo 5 N-(6-bromo-1,3benzotiazol-2-il)-2’-cloro5’-metoxi-6-metil-[4,4’bipiridina]-3-carboxamida -.¾ 65 98 3,73 489,1 / 491,1 B RMN 1H (400 MHz, CDCl3) δ 11,63 (s, 1H), 8,77 (s, 1H), 8,04 (s, 1H), 7,94 (d, J = 2,0 Hz, 1H), 7,29 (dd, J = 8,6; 2,0 Hz, 1H), 7,13 (s, 1H), 7,05 (s, 1H), 6,80 (d, J = 8,7 Hz, 1H), 3,70 (s, 3H), 2,64 (s, 3H) Exemplo 6 2’-cloro-N-{5-cloro[1,3]tiazol[5,4-d]pirimidin2-il}-5’-metoxi-6-metil[4,4’-bipiridina]-3carboxamida 1 χ X >= «-Μ* ' 22 95 3,08 447,0 / 449,0 B RMN 1H (400 MHz, DMSO-de) δ 13,50 (s, 1H), 9,12 (s, 1H), 8,88 (s, 1H), 8,17 (s, 1H), 7,59 (s, 1H), 7,47 (s, 1H), 3,61 (s, 3H), 2,61 (s, 3H).Example 7 2'-chloro-N-{5-chloro[1,3]thiazol[5,4-b]pyridin-2yl}-5'-methoxy-6-methyl-[4,4'bipyridine]-3-carboxamide —.fX .-ry. 1 χ 2H), 7.46 (s, 1H), 3.61 (s, 3H), 2.60 (s, 3H). Petition 870250080361, dated 08 / 09 / 2025, pages 407 / 513 126 / 231 Exemplo 8 3-(2-metoxifenil)-N{[1,3]tiazol[5,4d]pirimidin-2-il}piridina-4carboxamida ... X) / =\ 1 x 0· 1 11 100 2,41 364 B RMN 1H (400 MHz, DMSO-de) δ 13,33 (s, 1H), 9,20 (s, 1H), 9,03 (s, 1H), 8,76 (d, J = 4,9 Hz, 1H), 8,66 (s, 1H), 7,72 (d, J = 5,0 Hz, 1H), 7,44 7,36 (m, 2H), 7,09 (t, J = 6,9 Hz, 1H), 6,99 (d, J = 8,3 Hz, 1H), 3,51 (s, 3H). Exemplo 9 N-(6-bromo-1,3benzotiazol-2-il)-3-(2metoxifenil)piridina-4carboxamida 16 100 3,7 440,0 / 442,1 B RMN 1H (400 MHz, DMSO-de) δ 8,72 (s, 1H), 8,62 (s, 1H), 8,23 (s, 1H), 7,68 (d, J = 5,1 Hz, 2H), 7,57 (s, 1H), 7,38 (s, 2H), 7,10 - 7,05 (m, 1H), 6,98 (d, J = 8,3 Hz, 1H), 3,49 (s, 3H). Exemplo 10 3-(2-metoxifenil)-N{[1,3]tiazol[4,5-c]piridin-2il}piridina-4-carboxamida -XO . 1 χ X )=7 O' 1 6 99 1,73 363,1 B RMN 1H (400 MHz, DMSO-de) δ 9,00 (s, 1H), 8,76 - 8,70 (m, 1H), 8,62 (s, 1H), 8,41 - 8,35 (m, 1H), 8,02 (s, 1H), 7,72 7,67 (m, 1H), 7,42 - 7,33 (m, 2H), 7,10 - 7,03 (m, 1H), 6,99 - 6,94 (m, 1H), 3,48 (s, 3H).Exemplo 11 3-(2-metoxifenil)-N{[1,3]tiazol[4,5-b]piridin-2il}piridina-4-carboxamida -XO . 1 χ X )=7 O' 1 25 98 2,49 363,1 B RMN 1H (400 MHz, DMSO-de) δ 13,14 (s, 1H), 8,78 - 8,72 (m, 1H), 8,65 (s, 1H), 8,60 - 8,54 (m, 1H), 8,46 - 8,41 (m, 1H), 7,70 (d, J = 4,9 Hz, 1H), 7,45 - 7,35 (m, 2H), 7,36 - 7,29 (m, 1H), 7,09 (t, J = 7,6 Hz, 1H), 6,98 (d, J = 8,3 Hz, 1H), 3,50 (s, 3H). Exemplo 12 3-(2-metoxifenil)-N-[5(trifluorometil)-1,3benzotiazol-2-il]piridina-4carboxamida XX u ! ' 17 100 3,72 430,2 B RMN 1H (500 MHz, DMSO-de) δ 13,12 (s, 1H), 8,75 (d, J = 5,0 Hz, 1H), 8,65 (s, 1H), 8,24 (d, J = 8,2 Hz, 1H), 8,09 (s, 1H), 7,70 (d, J = 4,9 Hz, 1H), 7,65 (d, J = 10,4 Hz, 1H), 7,43 - 7,35 (m, 2H), 7,08 (t, J = 6,9 Hz, 1H), 6,97 (d, J = 8,4 Hz, 1H), 3,48 (s, 3H). Petição 870250080361, de 08 / 09 / 2025, pág. 408 / 513 127 / 231 Exemplo 13 N-(5-cloro-1,3-benzotiazol2-il)-3-(2metoxifenil)piridina-4carboxamida I Μ* ' 18 100 3,58 396,0 / 397,9 B RMN 1H (400 MHz, DMSO-de) δ 13,00 (s, 1H), 8,74 (d, J = 4,9 Hz, 1H), 8,64 (s, 1H), 8,01 (d, J = 8,5 Hz, 1H), 7,84 (d, J = 2,0 Hz, 1H), 7,68 (d, J = 5,0 Hz, 1H), 7,43 - 7,34 (m, 3H), 7,08 (t, J = 6,9 Hz, 1H), 6,97 (d, J = 8,3 Hz, 1H), 3,48 (s, 3H). Exemplo 14 3-(2-metoxifenil)-N{[1,3]tiazol[5,4-b]piridin-2il}piridina-4-carboxamida mJO -ρλ O' 10 100 2,57 363,1 B RMN 1H (500 MHz, DMSO-de) δ 13,00 (s, 1H), 8,75 (d, J = 5,0 Hz, 1H), 8,65 (s, 1H), 8,49 (dd, J = 4,7; 1,5 Hz, 1H), 8,16 - 8,12 (m, 1H), 7,69 (d, J = 5,0 Hz, 1H), 7,51 (dd, J = 8,2; 4,7 Hz, 1H), 7,43 - 7,35 (m, 2H), 7,11 - 7,07 (m, 1H), 6,98 (dd, J = 8,4, 1,0 Hz, 1H), 3,51 (s, 3H).Example 15 N-(1,3-benzothiazol-2-yl)-3(2-methoxyphenyl)pyridine-4carboxamide sO / =\ (m, 1H), 7.98 - 7.88 (m, 1H), 7.77 - 7.70 (m, 1H), 7.68 (d, J = 4.9 Hz, 1H), 7.45 7.32 (m, 3H), 7.32 - 7.24 (m, 1H), 7.09 - 7.03 (m, 1H), 6.98 (d, J = 8.1 Hz, 1H), 3.51 (s, 3H). Example 16 N-(5-cyano-1,3-benzothiazol2-yl)-3-(2methoxyphenyl)pyridine-4carboxamide Hz, 1H), 8.65 (s, 1H), 8.29 (d, J = 1.5 Hz, 1H), 8.22 (d, J = 8.2 Hz, 1H), 7.71 (dd, J = 8.2; 1.5 Hz, 1H), 7.69 (d, J = 5.0 Hz, 1H), 7.41 (dd, J = 7.5; 1.7Hz, 1H), 7.40 - 7.36 (m, 1H), 7.08 (td, J = 7.5; 1.0 Hz, 1H), 6.97 (d, J = 7.9 Hz, 1H), 3.48 (s, 3H). Petition 870250080361, dated 09 / 08 / 2025, pp. 409 / 513 128 / 231 Example 17 2'-chloro-5'-methoxy-6-methylN-[6-(morpholin-4-yl)-1,3benzothiazol-2-yl]-[4,4'bipyridine]-3-carboxamide 56 100 2.88 496.1 / 498.1 B 1H NMR (500 MHz, DMSO-de) δ 8.83 (s, 1H) 3.73 (m, 4H), 3.60 (s, 3H), 3.16 - 3.10 (m, 4H), 2.59 (s, 3H) Example 18 2'-chloro-5'-methoxy-6-methylN-(6-nitro-1,3-benzothiazol2-yl)-[4,4'-bipyridine]-3carboxamide .. 0.91 456.1 / 458.0 A 1H NMR (400 MHz, DMSO-de) δ 13.38 (s, 1H), 9.06 (s, 1H), 8.88 (s, 1H), 8.32 - 8.29 (m, 1H), 8.17 (s, 1H), 7.93 (d, J = 8.9Hz, 1H), 7.60 (s, 1H), 7.48 (s, 1H), 3.59 (s, 3H), 2.61 (s, 3H). General procedure D for SNAr reaction

[00296] To a solution of the required chlorothiazolopyrimidine (1 equiv., prepared using general procedure C) in DMF, ethanol, ethanol / DCE (1:1) or n-butanol, the desired amine (5 equiv.) was added. The reaction was heated to 80 or 100°C and monitored by LCMS until completion. If necessary, more amine (5 equiv.) was added. When complete, the reaction was concentrated under reduced pressure and the crude product purified by preparative HPLC using method A or method B. Example 19 - 4-(2-chloro-5-methoxy-4-pyridyl)-N-[5-[(3R)-3-hydroxypyrrolidin-1yl]thiazol[5,4-d]pyrimidin-2-yl]-6-methyl-pyridine-3-carboxamide

[00297] To a solution of 4-(2-chloro-5-methoxy-4-pyridyl)-N-(5-chlorothiazol[5,4-d]pyrimidin-2-yl)-6-methylpyridine-3-carboxamide (30.0 mg, 0.07 mmol) in a mixture of ethanol (0.5 mL) and DCE (0.5 mL), (3R)-pyrrolidin-3-ol (30 mg, 0.34 mmol) was added and the reaction was stirred at 80°C for Petition 870250080361, dated 08 / 09 / 2025, pages 410 / 513 129 / 231 hours. Another 5 equivalents of (3R)-pyrrolidin-3-ol were added and heating continued for 8 hours. Another 5 equivalents of (3R)-pyrrolidin-3-ol were added and heating continued for 18 hours. The reaction mixture was concentrated under reduced pressure and the residue dissolved in acetonitrile / water (1:1, 1 mL) and purified by preparative HPLC method A. The fractions containing the product were concentrated and lyophilized to give the title compound (7.0 mg, 21% yield) as a yellow powder. 1H NMR (500 MHz, DMSO-de) δ 8.84 (s, 1H), 8.71 (s, 1H), 8.16 (s, 1H), 7.54 (s, 1H), 7.42 (s, 1H), 4.96 (d, J = 3.5 Hz, 1H), 4.41 4.36 (m, 1H), 3.63 - 3.54 (m, 6H), 3.49 - 3.46 (m, 1H), 2.59 (s, 3H), 2.05 1.98 (m, 1H), 1.92 - 1.86 (m, 1H). LCMS (method B); RT 2.41 minutes (100%), m / z 498.1 / 500.1 (M+H)+

[00298] Examples 20 to 35 in Table 4 below were all synthesized using the general procedure D detailed above. Table 4 - Examples 20 to 35 synthesized with the general procedure D Example Yield LCMS Purity (%) LCMS RT (min.) m / z LCMS Method 1H NMR Example 201 2'-chloro-5'-methoxy-6-methyl- N-[5-(piperidin-1-yl)- [1,3]thiazol[5,4-d]pyrimidin2-yl]-[4,4'-bipyridine]-3carboxamide ...jv :' 9 100 3.86 496.5 / 498.5 B 1H NMR (400 MHz, DMSO-de) δ 12.86 (s, 1H), 8.83 (s, 1H), 8.72 (s, 1H), 8.17 (s, 1H), 7.56 (s, 1H), 7.44 (s, 1H), 3.82 - 3.72 (m, 4H), 3.62 (s, 3H), 2.59 (s, 3H), 1.68 - 1.58 (m, 2H), 1.58 - 1.48 (m, 4H). Petition 870250080361, dated 08 / 09 / 2025, pages 411 / 513 130 / 231 Exemplo 212 2’-cloro-N-[5-(4,4difluoropiperidin-1 -il)[l,3]tiazol[5,4-d]pirimidin2-il] -5 ’ -metoxi-6-metil[4,4’ -bipiridina] - 3 carboxamida T J 35 100 3,7 532,1 / 534,1 B RMN Ή (500 MHz, DMSO-ώ) δ 12,93 (s, 1H), 8,84 (s, 1H), 8,79 (s, 1H), 8,17 (s, 1H), 7,56 (s, 1H), 7,45 (s, 1H), 3,99 - 3,87 (m, 4H), 3,63 (s, 3H), 2,60 (s, 3H), 2,07 - 1,97 (m, 4H). Exemplo 223 2’-cloro-5’-metoxi-6-metil- N-[5-(morfolin-4-il)[l,3]tiazol[5,4-d]pirimidin2-il]-[4,4’-bipiridina]-3carboxamida ' T I 1“ AX’ 28 97 3,03 498,1 / 500,1 B RMN Ή (500 MHz, DMSO-ώ) δ 12,93 (s, 1H), 8,83 (s, 1H), 8,79 (s, 1H), 8,17 (s, 1H), 7,57 (s, 1H), 7,45 (s, 1H), 3,74 - 3,66 (m, 8H), 3,62 (s, 3H), 2,60 (s, 3H).Exemplo 234 2’-cloro-N-{5-[(3S)-3hidroxipirrolidin-1 -il] [l,3]tiazol[5,4-d]pirimidin2-il} -5 ’ -metoxi-6-metil[4,4’ -bipiridina] - 3 carboxamida 22 90 2,4 498,1 / 500,1 B RMN Ή (500 MHz, DMSO - de) δ 8,83 (s, 1H), 8,72 (s, 1H), 8,16 (s, 1H), 7,55 (s, 1H), 7,43 (s, 1H), 4,96 (d, J = 3,5 Hz, 1H), 4,41 4,36 (m, 1H), 3,65 3,53 (m, 6H), 3,50 3,45 (m, 1H), 2,59 (s, 3H), 2,05 - 1,98 (m, 1H), 1,93 - 1,87 (m, 1H). Exemplo 245 2’-cloro-5’-metoxi-6-metil- N-[5-(pirrolidin-l-il)[l,3]tiazol[5,4-d]pirimidin2-il]-[4,4’-bipiridina]-3carboxamida 31 100 3,21 482,2 / 484,2 B RMN Ή (500 MHz, DMSO-ώ) δ 12,84 (s, 1H), 8,82 (s, 1H), 8,75 (s, 1H), 8,17 (s, 1H), 7,57 (s, 1H), 7,46 (s, 1H), 3,63 (s, 3H), 3,55 - 3,49 (m, 4H), 2,60 (s, 3H), 1,98 - 1,91 (m, 4H). Petição 870250080361, de 08 / 09 / 2025, pág. 412 / 513 131 / 231 Example 256 2'-chloro-N-[5-(3,3difluoropirrolidin-1-il)[l,3]tiazol[5,4-d]pirimidin2-il]-5'-metoxi-6-methyl[4,4'-bipiridina]-3 carboxamide 42 98 3.33 518.2 / 520.2 B RMN Ή (400 MHz, DMSO-ri6) δ 12.93 (s, 1H), 8.83 (m, 2H), 8.17 (s, 1H), 7.57 (s, 1H), 7.46 (s, 1H), 3.95 (t, J = 13.1 Hz, 2H), 3.77 (t, J = 7.4 Hz, 2H), 3.62 (s, 3H), 2.60 (m, 5H). Exemplo 267 2'-chloro-N-{5-[(3R)-3hidroxipirrolidin-1 -il] [l,3]tiazol[5,4-d]pirimidin2-il} -5 ' -metoxi-6-metil[4,4' -bipiridina] - 3 carboxamida TJ r ,χ / ϊ 21 100 2.41 498.1 / 500.1 B RMN Ή (500 MHz, DMSO-ri6) δ 8.84 (s, 1H), 8.71 (s, 1H), 8.16 (s, 1H), 7.54 (s, 1H), 7.42 (s, 1H), 4.96 (d, J = 3.5 Hz, 1H), 4.41 4.36 (m, 1H), 3.63 3.54 (m, 6H), 3.49 3.46 (m, 1H), 2.59 (s, 3H), 2.05 - 1.98 (m, 1H), 1.92 - 1.86 (m, 1H).Example 278 2'-chloro-N-[5-(1,1-dioxo- 1 Z6-thiomorpholin-4-yl)[l,3]thiazol[5,4-d]pyrimidin2-yl] -5 ' -methoxy-6-methyl[4,4' -bipyridine] - 3 carboxamide TI JW^· 9 100 2.78 546.1 / 548.0 B NMR Ή (400 MHz, DMSO-ri6) δ 12.98 (s, 1H), 8.87 (s, 1H), 8.16 (s, 1H), 7.56 - 7.37 (m, 3H), 4.23 (s, 4H), 3.61 (s, 3H), 3.17(s, 4H), 2.59(s, 3H). Example 289 2'-chloro-5'-methoxy-6-methylN-[5-(4-methylpiperazin-1yl)-[l,3]thiazol[5,4d]pyrimidin-2-yl] - [4,4 ' bipyridine] - 3 -carboxamide 42 100 1.76 511 / 513.1 B NMR Ή (500 MHz, DMSO-ri6) δ 8.84(s,1H), 8.76(s,1H), 8.17(s,1H), 7.57(s,1H), 7.45(s,1H), 3.79 3.73(m,4H), 3.63(s,3H), 2.60(s,000). 3H), 2.44 - 2.39 (m, 4H), 2.24 (s, 3H). Petition 870250080361, 08 / 09 / 2025, p. 413 / 5 132 / Exemplo 2910 2’-cloro-5’-metoxi-6-metil- N-(5-{2-oxa-6azaspiro[3,3]heptan-6-il}[1,3]tiazol[5,4-d]pirimidin2-il)-[4,4’-bipiridina]-3carboxamida 21 100 2,55 510,1 / 512,1 B RMN 1H (500 MHz, DMSO - de) δ 12,92 (s, 1H), 8,83 (s, 1H), 8,75 (s, 1H), 8,16 (s, 1H), 7,56 (s, 1H), 7,44 (s, 1H), 4,73 (s, 4H), 4,24 (s, 4H), 3,61 (s, 3H), 2,59 (s, 3H). Exemplo 3011 2’-cloro-5’-metoxi-N-{5[(2-metoxietil)amino][1,3]tiazol[5,4-d]pirimidin2-il}-6-metil-[4,4’bipiridina]-3-carboxamida 38 100 2,69 486,0 / 488,1 B RMN 1H (400 MHz, DMSO-de) δ 12,86 (s, 1H), 8,85 (s, 1H), 8,66 (s, 1H), 8,17 (s, 1H), 7,55 (s, 1H), 7,43 (s, 1H), 7,28 (s, 1H), 3,63 (s, 3H), 3,50 - 3,45 (m, 4H), 3,27 (s, 3H), 2,60 (s, 3H).Exemplo 3112 2'-chloro-N-[5-(3hidroxiazetidin-1-il)[1,3]tiazol[5,4-d]pirimidin2-il]-5'-metoxi-6-metil[4,4'-bipiridina]-3carboxamida 7 100 2.27 484.1 / 486.0 B RMN 1H (500 MHz, DMSO-de) δ 12.87 (s, 1H), 8.88 (s, 1H), 8.64 (s, 1H), 8.15 (s, 1H), 7.50 (s, 1H), 7.37 (s, 1H), 5.67 (d, J = 6.7 Hz, 1H), 4.59 - 4,52 (m, 1H), 4.28 - 4.21 (m, 2H), 3.82 - 3.76 (m, 2H), 3.62 (s, 3H), 2.58 (s, 3H). Exemplo 3213 2'-chloro-5'-metoxi-N-[5-(3metoxipirrolidin-1-il)[1,3]tiazol[5,4-d]pirimidin- 2-il]-6-metil-[4,4'-bipiridina]-3-carboxamida 32 99 2.93 512.1 / 514.1 B RMN 1H (500 MHz, DMSO-de) δ 12.87 (s, 1H), 8.83 (s, 1H), 8.76 (s, 1H), 8.18 (s, 1H), 7.57 (s, 1H), 7.46 (s, 1H), 4.08 (s, 1H), 3.69 - 3.57 (m, 6H), 3,49 (q, J = 8.7 Hz, 1H), 3.27 (s, 3H), 2.60 (s, 3H), 2.10 - 2.04 (m, 2H). Petition 870250080361, on 09 / 08 / 2025, page. 414 / 513 133 / 231 Exemplo 3314 2'-chloro-N-[5-(4hidroxipiperidin-1 -il)[l,3]tiazol[5,4-d]pirimidin2-il] -5' -metoxi-6-metil[4,4' -bipiridina] - 3 carboxamida EE» O 28 100 2.66 512.1 / 514.1 B RMN Ή (400 MHz, DMSO - de) δ 12.87 (s, 1H), 8.83 (s, 1H), 8.72 (s, 1H), 8.16 (s, 1H), 7.55 (s, 1H), 7.44 (s, 1H), 4.73 (d, J = 4.3 Hz, 1H), 4.33 4.22 (m, (2H), 3.74 (dq, J = 8.5; 4.1 Hz, 1H), 3.62 (s, 3H), 2.59 (s, 3H), 1.83 - 1.74 (m, 2H), 1.40 - 1.29 (m, 2H).Exemplo 3415 2’-cloro-5’-metoxi-6-metil- N-{5-[(lS,4S)-2-oxa-5azabiciclo[2,2,1 ]heptan-5il]-[l,3]tiazol[5,4d]pirimidin-2-il} - [4,4 ’ bipiridina] - 3 -carboxamida 24 100 2,74 510,1 / 512,1 B RMN Ή (400 MHz, DMSO-ris) δ 12,88 (s, 1H), 8,84 (s, 1H), 8,74 (s, 1H), 8,17 (s, 1H), 7,55 (s, 1H), 7,44 (s, 1H), 4,96 (s, 1H), 4,67 (s, 1H), 3,81 (d, J = 5,8 Hz, 1H), 3,68 (d, J = 7,3 Hz, 1H), 3,62 (s, 3H), 3,52 (d, J = 9,3 Hz, 1H), 3,42 (d, J = 11,4 Hz, 1H), 2,59 (s, 3H), 1,94 (d, J = 7,3 Hz, 1H), 1,87 (d, J = 9,5 Hz, 1H) Exemplo 3516 2’-cloro-N-[5-(3cianopiperidin-1 -il)[l,3]tiazol[5,4-d]pirimidin2-il] -5 ’ -metoxi-6-metil[4,4’ -bipiridina] - 3 carboxamida Λ 18 100 3,27 521,1 / 523,1 B RMN 1H (400 MHz, DMSO-ris) δ 12,93 (s, 1H), 8,84 (s, 1H), 8,78 (s, 1H), 8,16 (s, 1H), 7,56 (s, 1H), 7,45 (s, 1H), 4,24 - 4,17 (m, 1H), 4,02 - 3,94 (m, 1H), 3,90 - 3,84 (m, 1H), 3,68 - 3,63 (m, 1H), 3,62 (s, 3H), 3,14 - 3,08 (m, 1H), 2,59 (s, 3H), 1,99 - 1,88 (m, 2H), 1,72 - 1,55 (m, 2H). Table 5 - Solvent and reaction temperature used in the preparation of Examples in Table 4 above_________________________________________ Footnote in Table 4 above: Reaction Solvent | Reaction Temperature (°C) | 1 DMF 80 | 2 Ethanol / DCE 80 | 3 Ethanol / DCE 80 | 4 Ethanol / DCE 80 | 5 Ethanol / DCE 80 | 6 Ethanol / DCE 80 | 7 Ethanol / DCE 80 Petition 870250080361, dated 08 / 09 / 2025, pages 415 / 513 134 / 231 8 Ethanol / DCE 80 9 Ethanol / DCE 80 10 Ethanol / DCE 80 11 n-Butanol 100 12 Ethanol 80 13 Ethanol 80 14 DMF 80 15 Ethanol 80 16 Ethanol / DCE 80 Examples 36A and 36B - Synthesis of 2'Ξchloro25%meLθXL·62meLil2NΣLM2oxopipcπdinvbl·ilL·L3ΣbeΠ.ZOliazoL·22 Step A - N-(6-amino-1,3-benzothiazol-2-yl)-4-(2-chloro-5-methoxy-4-pyridyl)-6methyl-pyridine-3-carboxamide (Example 36A)

[00299] A stirred solution of 4-(2-chloro-5-methoxy-4-pyridyl)-6-methyl-N-(6-nitro-1,3-benzothiazol-2-yl)pyridine-3-carboxamide (1.1 g, 2.41 mmol, prepared using general procedure C) in ethanol (11 mL) and water (4.4 mL) was washed with nitrogen for 5 minutes, then powdered iron (0.9 g, 16.1 mmol) and solid ammonium chloride (1.2 g, 22.4 mmol) were added. The reaction mixture was stirred at 60°C for 30 minutes, then filtered through a layer of celite, washed with ethyl acetate (20 mL), and the resulting filtrate was washed with water (15 mL). The organic layer was separated, dried (Na2SÜ4), and concentrated under reduced pressure. The residue was purified by automated chromatography with Biotage Isolera™ (Sfar Duo 10g) using a 0-10% methanol gradient in DCM to provide the title compound. Petition 870250080361, dated 08 / 09 / 2025, pages 416 / 513 135 / 231 (454 mg, 44% yield) as a yellowish brown solid. 1H NMR (400 MHz, DMSO-de) δ 12.59(s,1H), 8.82(s,1H), 8.17(s,1H), 7.55(s,1H), 7.46 - 7.41 (m, 2H), 7.00 (d, J = 2.2 Hz, 1H), 6.73 (dd, J = 8.6; 2.3 Hz, 1H), 5.17 (s, 2H), 3.62 (s, 3H), 2.60 (s, 3H). LCMS (method B); RT 1.93 minutes (99%), m / z 424.5 / 426.5 (M+H)+. Stage________B________2l·çloroΣ5Σmethox^6-methy^NΣI6=(2oxopi^^yl)-1,3-benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide (Example 36B) .Nx_Cl O SCt O 3,%%^^^^ II Λ H h3c^%t

[00300] To a chilled, stirred solution of N-(6-amino-1,3-benzothiazol-2-yl)-4-(2-chloro-5-methoxy-4-pyridyl)-6-methylpyridine-3-carboxamide (30.0 mg, 0.07 mmol) and DIPEA (12 μL, 0.07 mmol) in THF (0.6 mL), a solution of 5-bromopentanoyl chloride (11 μL, 0.08 mmol) in THF (0.6 mL) was added dropwise, and the reaction mixture was stirred for 15 minutes. Then, it was treated portion by portion with potassium tert-butoxide (30.0 mg, 0.27 mmol). Stirring was continued for 30 minutes. The mixture was treated with water (5 mL) and brine (5 mL) and extracted with ethyl acetate (2 x 15 mL). The combined organic extracts were dried (MgSO4), filtered, and evaporated under reduced pressure. The crude product was purified by preparative HPLC method A. The fractions containing the product were evaporated under reduced pressure and lyophilized to provide the title compound (6.8 mg, 19% yield) as a white powder.1H NMR (500 MHz, DMSO- de) δ 12.97 (s, 1H), 8.87 (s, 1H), 8.16 (s, 1H), 7.87 (s, 1H), 7.75 (d, J = 8.6 Hz, 1H), (1H), 7,4.58 7.34 (dd, J = 8.5; 2.1 Hz, 1H), 3.64 (t, J = 5.7 Hz, 2H), 3.60 (s, 3H), 2.61 (s, 3H), 2.41 (t, J = 6.3 Hz, 2H, 1.3). LCMS (method B); RT 2.79 minutes (100%), m / z 508.2 / 510.1(M+H)+. Petition 870250080361, dated 08 / 09 / 2025, p. 417 / 513 136 / 231 Example 37 - Synthesis of 2'-chloro-N-r5-(5,6-dihydro-2H-pyran-3yl)-[ 1,31thiazol[5,4-b]pyridin-2yl]-5 ' -methoxy-6-methyl- [4,4 ' -bipyridine] -amide Λ Stage A . Stage B ,r. < > Stage C / \ Μ-'Λ,z''' * ' * ' '' * X / ®” λ''; ••'vj li' * | Stage D * ' ''T' ·< ' '.m '' >5- .'*xr>'' and 'f ' Stage A N-(5-chlorothiazol[5,4-b]pyridin-2-yl)tert-butyl carbamate

[00301] A solution of 5-chlorothiazol[5,4-b]pyridin-2-amine (100 mg, 0.54 mmol) in DCE (2.5 mL), DIPEA (0.20 mL, 1.15 mmol) and N,N-dimethylpyridin-4-amine (6.17 mg, 0.05 mmol) was added at room temperature. To the previous solution, di-tert-butyl dicarbonate (124 mg, 0.57 mmol) was added and the resulting mixture was stirred at room temperature for 4 hours. Another 0.5 equivalent of N,N-dimethylpyridin-4-amine and di-tert-butyl dicarbonate was added and stirring continued for 18 hours. The mixture was diluted with DCM and washed with a solution of water and brine (10 mL). The combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure. The crude product was purified by automated chromatography with Biotage Isolera™ (10g, Sfar Duo) eluting with 0-50% ethyl acetate in heptanes to give the title compound (137 mg, 89% yield) as a colorless powder.NMR Ή (500 MHz, DMSO-in / d) δ 12.09 (s, 1H), 8.08 (d, J = 8.5 Hz, 1H), 7.52 (d, J = 8.4 Hz, 1H), 1.52 (s, 9H). LCMS (method A); 0.97 min (100%), m / z 230.0 / 232.0 (MιΒη+Η)+. Step B N-p5-(3,6-dihydro-2H-pyran-5-iDthiazoir5,4-b]pyridin-2-yl]tert-butyl carbamate Petition 870250080361, of 08 / 09 / 2025, p. 418 / 513 137 / 231

[00302] To a solution of tert-butyl N-(5-chlorothiazol[5,4-b]pyridin-2-yl)carbamate (130 mg, 0.46 mmol) in 1,4-dioxane (1.8 mL) and water (0.45 mL) in a pressure flask, 2-(3,6-dihydro2H-pyran-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolan (115 mg, 0.55 mmol) and dipotassium carbonate (157 mg, 1.14 mmol) were added. The mixture was degassed under nitrogen before palladium dichloride DTBPF (30 mg, 0.05 mmol) was added, and the mixture was stirred at 90°C for 3 hours. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (20 mL). The solution was washed with water and brine solution (10 mL), then dried (Na2SÜ4) and concentrated under reduced pressure. The crude product was purified by automatic chromatography with Biotage Isolera™ (25 g, Sfar Duo) eluting with 0-50% ethyl acetate in heptanes to give the title compound (92 mg, 58% yield) as a colorless powder.1H NMR (500 MHz, DMSO-de) δ 11.91 (s, 1H), 7.97 (d, J = 8.6 Hz, 1H), 7.64 (d, J = 8.6 Hz, 1H), 6.82 - 6.78 (m, 1H), 4.58 - 4.54 (m, 2H), 3.75 (t, J = 5.5 Hz, 2H), 2.33 - 2.29 (m, 2H), 1.52 (s, 9H). LCMS (method A); RT 0.96 minute (96%), m / z 334.1 (M+H)+. Step C 5-(3,6-dihydro-2H-pyran-5-yl)thiazol[5,4-b]pyridin-2-amine N*'\ / \ / ii no H^N''''^S

[00303] To a solution of tert-butyl N-[5-(3,6-dihydro-2H-pyran-5-yl)thiazol[5,4b]pyridin-2-yl]carbamate (20.0 mg, 0.06 mmol) in acetonitrile (0.25 mL), 4 M hydrogen chloride in 1,4-dioxane (0.22 mL, 0.86 mmol) was added and the mixture was stirred at room temperature for 18 hours.

[00304] The reaction mixture was concentrated under reduced pressure and the residue dissolved in DCM / methanol 1:1 (0.5 mL). 4 M hydrogen chloride in 1,4-dioxane (0.22 mL, 0.86 mmol) was added. Petition 870250080361, dated 09 / 08 / 2025, pp. 419 / 513 138 / 231

[00305] The mixture was stirred at room temperature for 72 hours. The reaction mixture was concentrated under reduced pressure and the resulting solid dissolved in methanol and loaded into an Ig SCX ion exchange cartridge. The cartridge was washed with methanol (5 mL) and then with 2M ammonia in methanol (5 mL). The ammonia filtrate was concentrated under reduced pressure to give (12 mg, 80% yield) a colorless powder, which was used immediately without further purification. LCMS (method A) RT 0.60 minute (87%), m / z 234.5 (M+H)+. Step D 4-(2-chloro-5-methoxy-4-pyridyl)-N-r5-(3,6-dihydro-2H-pyran-5yl)thiazol[5,4-b]pyridin-2-yl]-6-methyl-pyridine-3-carboxamide

[00306] Prepared with the general procedure C detailed above to provide the title compound (3.5 mg, 15% yield) as a colorless powder. NMR Ή (500 MHz, DMSO-íZ6) δ 13.05 (s, 1H), 8.85 (s, 1H), 8.16 (s, 1H), 8.08 (d, J = 8.5 Hz, 1H), 7.72 (d, J = 8.6 Hz, 1H), 7.58 (s, 1H), 7.47 (s, 1H), 6.87 - 6.80 (m, 1H), 4.58 (d, J = 2.3 Hz, 2H), 3.75 (t, J = 5.5 Hz, 2H), 3.61 (s, 3H), 2.60 (s, 3H), 2.34 - 2.31 (m, 2H). LCMS (method B) RT 3.22 minutes (100%) m / z 494.1 / 496.1 (M+H)+. Example 38 - Synthesis of 2'-chloro-N-r6-(5-chloropyridin-2yl)-1,3-benzothiazol-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide Step A Tert-butyl N-(6-bromo-1,3-benzothiazol-2-yl)carbamate Petition 870250080361, dated 09 / 08 / 2025, pp. 420 / 513 139 / 231 CH3 ON H3C I IIIIH3CoN H

[00307] Prepared in a manner analogous to N-(5-chlorothiazol[5,4-b]pyridin2-yl)carbamate detailed above to provide the title compound (665 mg, 58% yield) as an orange solid. 1H NMR (400 MHz, DMSO- δ 8.18 (d, J = 2.0 Hz, 1H), 7.60 (d, J = 8.5 Hz, 1H), 7.52 (dd, J = 8.5; 2.0 Hz, 1H), 1.51 (s, 9H). LCMS (method B) RT 4.09 minutes (74%), m / z 329.0 / 331.0 (M+H)+. Step B tert-Butyl N-[6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzothiazol-2yl]carbamate)

[00308] To a solution of tert-butyl N-(6-bromo-1,3-benzothiazol-2-yl)carbamate (150 mg, 0.46 mmol) in 1,4-dioxane (2.5 mL) in a pressure flask, 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (231 mg, 0.91 mmol) and potassium acetate (223 mg, 2.28 mmol) were added. The mixture was degassed under nitrogen before palladium dichloride DPPF (33 mg, 0.05 mmol) was added. The mixture was stirred at 90°C for 3 hours. The reaction mixture was cooled to room temperature and filtered through celite. The celite layer was washed with ethyl acetate and the filtrate purified by automatic chromatography with Biotage Isolera™ (25g, Sfar duo) eluting with 0-50% ethyl acetate in heptanes to give the title compound (210 mg, 86% yield), as a light yellow glass that began to crystallize when left to stand at room temperature.1H NMR (400 MHz, DMSO-de) δ 11.85 (br s, 1H), 8.22 (s, 1H), 7.68 - 7.63 (m, 2H), 1.51 (s, 9H), 1.31 (s, 12H). LCMS (method A); RT 1.16 minutes (100%), m / z 377.2 (M+H)+. Step C Tert-butyl N-[6-(5-chloro-2-pyridyl)-1,3-benzothiazol-2-yl]carbamate Petition 870250080361, dated 08 / 09 / 2025, pages 421 / 513 140 / 231

[00309] To a solution of tert-butyl N-[6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzothiazol-2-yl]carbamate (210 mg, 0.39 mmol) in 1,4-dioxane (1.6 mL) and water (0.4 mL) in a pressure flask, 2-bromo-5-chloropyridine (98 mg, 0.51 mmol) and dipotassium carbonate (135 mg, 0.98 mmol) were added. The mixture was degassed under nitrogen before palladium dichloride DTBPF (26 mg, 0.04 mmol) was added. The mixture was stirred at 90°C for 3 hours. The reaction was cooled to room temperature, diluted with ethyl acetate (20 mL), and washed with water and brine (10 mL). After the organic layer was separated, a precipitate began to form. The solution was cooled in an ice bath for 30 minutes, then the precipitate was filtered. The filtered cake was washed with ether and dried under a stream of nitrogen. LCMS showed that the solid was a pure product (45 mg).The filtrate was concentrated under reduced pressure and purified by automatic chromatography with Biotage Isolera™ (25g, Sfar Duo) eluting with 0-100% ethyl acetate in heptanes to provide a second crop of product. Both crops were combined to provide the title compound (109 mg, 77% yield) as a beige powder. 1H NMR (500 MHz, DMSO-de) δ 11.88 (br s, 1H), 8.70 (d, J = 2.5 Hz, 1H), 8.67 (d, J = 1.9 Hz, 1H), 8.13 (dd, J = 8.5; 1.9 Hz, 1H), 8.07 (d, J = 8.7 Hz, 1H), 8.01 (dd, J = 8.6; 2.5 Hz, 1H), 7.75 (d, J = 8.5 Hz, 1H), 1.52 (s, 9H). LCMS (method A); RT 1.15 minutes, m / z 362 / 364.0 (M+H)+. Step D 6-(5-chloro-2-pyridyl)-1,3-benzothiazol-2-amine; dihydrochloride

[00310] To a suspension of tert-butyl N-[6-(5-chloro-2-pyridyl)-1,3-benzothiazol-2-yl]carbamate (109 mg, 0.3 mmol) in 1,4-dioxane (0.5 mL) at 0°C, 4 M hydrogen chloride in 1,4-dioxane (1.1 mL, 4.52 mmol) was added dropwise. Once the addition was complete, the mixture was heated until Petition 870250080361, dated 09 / 08 / 2025, pp. 422 / 513 141 / 231 room temperature and stirred for 18 hours. The starting material precipitated from the solution. 1 mL of acetonitrile was added to aid solubility and stirring continued for 24 hours. The mixture was concentrated under reduced pressure and the residue dried azeotropically with diethyl ether to give the title compound (109 mg, quantitative yield) as a colorless powder, which was used immediately without further purification. LCMS (method A); RT 0.75 minute (100%) m / z 262.1 / 264.1 (M+H)+. Step E 4-(2-chloro-5-methoxy-4-pyridyl)-N-[6-(3-chloro-2-pyridyl)-1,3benzothiazol-2-yl]-6-methyl-pyridine-3-carboxamide

[00311] Prepared with the general procedure C detailed above to provide the title compound (83 mg, 54% yield) as a colorless powder. NMR Ή (500 MHz, DMSO-í / 6) δ 13.08 (s, 1H), 8.87 (s, 1H), 8.73 8.70 (m, 2H), 8.20 (dd, J = 8.5; 1.9 Hz, 1H), 8.17 (s, 1H), 8.09 (d, J = 8.6 Hz, 1H), 8.03 (dd, J = 8.6; 2.5 Hz, 1H), 7.86 (d, J = 8.5 Hz, 1H), 7.59 (s, 1H), 7.47 (s, 1H), 3.61 (s, 3H), 2.61 (s, 3H). LCMS (method B); RT 3.92 minutes (100%) m / z 522 / 524 (M+H)+. Example 39 - Synthesis of N-r6-(5-chloropyridin-2-yl)-1,3-benzothiazol-2yl1-3-(2-methoxyphenyl)pyridine-4-carboxamide

[00312] Synthesized using general procedure C from 6-(5-chloropyridin-2-yl)-1,3-benzothiazol-2-amine hydrochloride, prepared in a manner analogous to that shown above, to provide the title compound (40 mg, 19% yield) as a colorless powder. NZHMR (500 MHz, DMSO-t / b) δ 12.96 (br s, 1H), 8.5-8.9 (m, 4H), 8.19 (dd, 1H, J=1.8; 8.6 Hz), 8.0-8.1 (m, 1H), 8.02 (dd, 1H, J=2.6; 8.6 Hz), 7.85 (d, 1H, J=8.5 Hz), 7.69 (d, 1H, J=4.8 Petition 870250080361, dated 08 / 09 / 2025, pages 423 / 513 142 / 231 Hz), 7.3-7.4 (m, 2H), 7.0-7.1 (m, 1H), 6.9-7.0 (m, 1H), 3.4-3.6 (m, 3H). ECMS (method B) RT 2.72 minutes (87%), m / z 473.1 / 475.1 (M+H)+. Example 40 - Synthesis of 2'-chloro-N-[6-(3-hydroxyoxolan-3yl)-1,3-benzothiazol-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide

[00313] Butyllithium 1.6 M in hexane (50 μE, 0.08 mmol) was added dropwise to a solution of N-(6-bromo-1,3-benzothiazol-2-yl)-4(2-chloro-5-methoxy-4-pyridyl)-6-methylpyridine-3-carboxamide (16 mg, 0.03 mmol, prepared with the general procedure C detailed above) in THF (0.5 mE) at -78°C. The reaction mixture was stirred at -78°C for a further 15 minutes. Then, dihydrofuran-3(2H)-one (4.0 mg, 0.05 mmol) was added dropwise as a solution in THF (0.2 mE) to the reaction mixture and stirred for 2 hours at -78°C. A saturated aqueous solution of ammonium chloride was added (10 mE) and the mixture extracted with diethyl ether (2 x 10 mE) and ethyl acetate (1 x 10 mE) due to the low solubility of the product. The organic extracts were combined, dried (Na2SO4), filtered, and evaporated under reduced pressure.The crude product was purified by automated chromatography with Biotage Isolera™ (Sfar Duo, 10 g) eluting with a gradient of 0-100% ethyl acetate in heptanes increasing to 10% methanol in ethyl acetate. The fractions containing the product were concentrated under reduced pressure and the product was further purified by preparative HPEC method A to give the title compound (1.6 mg, 8% yield) as a white powder. 1H NMR (400 MHz, CDCl3) δ 8.89 (s, 1H), 8.05 (s, 1H), 7.85 - 7.81 (m, 1H), 7.46 - 7.39 (m, 1H), 7.36 - 7.32 (m, 2H), 7.21 (d, J = 3.0 Hz, 2H), 4.08 - 3.91 (m, 2H), 3.76 - 3.72 (m, 4H), 3.66 (d, J = 9.2 Hz, 1H), 2.06 - 1.98 (m, 2H). ECMS (method B); RT 2.91 minutes (86%), m / z 497.2 / 499.2 (M+H)+. Petition 870250080361, dated 09 / 08 / 2025, pp. 424 / 513 143 / 231 Example 41 - Synthesis of 2'2cloI02N%6ΣmeLaΠθsullòπamldo%3benzoLiazθL·2-ΠL5%mctoxH6Σmcύl·LA [4'-bipyridine]-3-carboxamide

[00314] To a solution of N-(6-amino-1,3-benzothiazol-2-yl)-4-(2-chloro-5-methoxy-4-pyridyl)-6-methylpyridine-3-carboxamide (30.0 mg, 0.07 mmol), prepared in a manner analogous to that shown above, and DIPEA (15 μE, 0.08 mmol) in DCM (0.5 mL), sulfonyl methane chloride (6 μE, 0.08 mmol) at 0°C was added. Once the addition was complete, the reaction mixture was heated to room temperature and stirred for 4 hours. Another 1.2 equivalents of DIPEA and sulfonyl methane chloride were added and the reaction continued at room temperature for 2 hours. The mixture was diluted with DCM and washed with saturated aqueous NaHCO3 solution. The organic extracts were dried (Na2SO4) and concentrated to give the crude product as a yellow glass. The crude product was purified by preparative HPLC method A to give the title compound (10 mg, 28% yield) as a colorless powder.1H NMR (500 MHz, DMSO-de) δ 12.90 (s, 1H), 9.77 (s, 1H), 8.84 (s, 1H), 8.15 (s, 1H), 7.78 (s, 1H), 7.72 (d, J = 8.8 Hz, 1H), 7.57 (s, 1H), 7.45 (s, 1H), 7.30 (d, J = 8.8 Hz, 1H), 3.60 (s, 3H), 2.99 (s, 3H), 2.60 (s, 3H). LCMS (method B); RT 2.63 minutes (100%) m / z 504.0 / 506.0 (M+H)+. Examples 42 to 44

[00315] Examples 42 to 44 listed in Table 6 below were synthesized using the general C procedure described earlier. Petition 870250080361, dated 09 / 08 / 2025, pp. 425 / 513 144 / 231 Table 6 Exemplo Rendimento Pureza LCMS (%) LCMS RT (min.) m / z Método de LCMS RMN 1H •UC®. .- / 3 1 X X >= jOt· Exemplo 42 2’-cloro-5’-metoxi-6-metilN-{[1,3]tiazol[5,4d]pirimidin-2-il}-[4,4’bipiridina] - 3-carboxamida 6 100 2,46 413,0 / 415,0 B RMN 1H (500 MHz, DMSO-d6) δ 13,38 (s, 1H), 9,15 - 8,89 (m, 3H), 8,15 (s, 1H), 7,53 (s, 1H), 7,40 (s, 1H), 3,61 (s, 3H), 2,59 (s, 3H). 'XX X^X7 ...Xj : Exemplo 43 2’-cloro-5’-metoxi-6-metilN-[6-(metilsulfanil)-1,3benzotiazol-2-il]-[4,4’bipiridina] - 3-carboxamida 14 100 3,47 457,0 / 459,0 B RMN 1H (400 MHz, DMSO-d6) δ 12,93 (s, 1H), 8,84 (s, 1H), 8,16 (s, 1H), 7,91 (d, J = 2,0 Hz, 1H), 7,69 (d, J = 8,5 Hz, 1H), 7,57 (s, 1H), 7,46 (s, 1H), 7,36 (dd, J = 8,6; 1,9 Hz, 1H), 3,59 (s, 3H), 2,60 (s, 3H), 2,53 (s, 3H).XXX / =7 jy ! Example 44 2'-chloro-5'-methoxy-6-methyl- N-{[1,3]thiazol[5,4-c]pyridin2-yl}-[4,4'-bipyridine]-3carboxamide 24 100 1.11 412.0 / 414.0 D 1H NMR (500 MHz, DMSO-d6) δ 13.09 (s, 1H), 8.87 (s, 1H), 8.49 (dd, J = 4.7; 1.5 Hz, 1H), 8.17 (s, 1H), 8.14 (d, J = 8.2 Hz, 1H), 7.59 (s, 1H), 7.51 (dd, J = 8.2; 4.7 Hz, 1H), 7.47 (s, 1H), 3.62 (s, 3H), 2.61 (s, 3H). Examples 45 to 53

[00316] Examples 45 to 53 and intermediates 7 and 8 in Table 7 below were synthesized using the general procedure D described above, using the conditions described in Table 8 of footnotes. Petition 870250080361, dated 09 / 08 / 2025, pp. 426 / 513 145 / 231 Table 7 Example Yield LCMS Purity (%) LCMS RT (min.) m / z LCMS Method 1H NMR Example 453 N-[5-(4-acetylpiperazin-1yl)-[1,3]thiazol[5,4d]pyrimidin-2-yl]-2'-chloro5'-methoxy-6-methyl-[4,4'bipyridine] - 3-carboxamide 35 100 2.66 539.1 / 541.1 B 1H NMR (400 MHz, DMSO-de) δ 12.82 (s, 1H), 8.83 (s, 1H), 8.79 (s, 1H), 8.17 (s, 1H), 7.57 (s, 1H), 7.45 (s, 1H), 3.85 3.77 (m, 2H), 3.77 - 3.71 (m, 2H), 3.62 (s, 3H), 3.57 - 3.50 (m, 4H), 2.60 (s, 3H), 2.05 (s, 3H). Cs.aCI OH í| | Example 462 472.1 / 474.1 B 1H NMR (400 MHz, DMSO-de) δ 8.87 (s, 1H), 8.58 (s, 1H), 8.15 (s, 1H), 7.50 (s, 1H), 7.37 (s, 1H), 7.11 - 7.03 (m, 1H), 4.67 (s, 1H), 3.63 (s, 3H), 3.52 (t, J = 6.3 Hz, 2H), 2.58 (s, 3H), a methylene group obscured by the water peak and a non-interchangeable proton not observed. .Ns___„Cl H . .% s H,C Ή Exemplo 474 2’-cloro-5’-metoxi-N-[5-(3metoxiazetidin-1-il)- [1,3]tiazol[5,4-d]pirimidin2-il]-6-metil-[4,4’bipiridina] - 3-carboxamida 46 99 2,74 498,1 / 500,1 B RMN 1H (400 MHz, DMSO-de) δ 12,92 (s, 1H), 8,86 (s, 1H), 8,72 (s, 1H), 8,17 (s, 1H), 7,54 (s, 1H), 7,42 (s, 1H), 4,35 4,29 (m, 1H), 4,26 (dd, J = 8,6; 6,5 Hz, 2H), 3,89 (dd, J = 10,1; 3,7 Hz, 2H), 3,63 (s, 3H), 3,26 (s, 3H), 2,59 (s, 3H). OH 'ΑΧ ,-Ο-ί NΛ H-C^ Exemplo 482 2’-cloro-N-{5-[(4hidroxiciclo-hexil)amino][1,3]tiazol[5,4-d]pirimidin2-il}-5’-metoxi-6-metil[4,4’-bipiridina]-3carboxamida 13 100 2,42 526,1 / 528,1 B RMN 1H (500 MHz, DMSO-de) δ 12,80 (s, 1H), 8,84 (s, 1H), 8,60 (s, 1H), 8,21 - 8,06 (m, 1H), 7,51 (s, 1H), 7,39 (s, 1H), 7,22 - 6,96 (m, 1H), 4,52 (d, J = 4,4 Hz, 1H), 3,72 3,38 (m, 5H), 2,57 (s, 3H), 1,95 - 1,76 (m, 4H), 1,32 - 1,16 (m, 4H). Petição 870250080361, de 08 / 09 / 2025, pág. 427 / 513 146 / 231 “Xã a9xk Exemplo 492 rac-2’-cloro-N-(5{[(lR,3S)-3hidroxiciclopentil]amino} [l,3]tiazol[5,4-d]pirimidin2-il)-5 ’ -metoxi-6-metil[4,4’ -bipiridina] - 3 carboxamida 18 100 2,50 512,1 / 514,1 B RMN Ή (500 MHz, DMSO-ώ) δ 12,83 (s, 1H), 8,84 (s, 1H), 8,65 (s, 1H), 8,29 - 8,05 (m, 1H), 7,55 (s, 1H), 7,43 (s, 1H), 7,22 (s, 1H), 4,64 (d, J = 4,1 Hz, 1H), 4,22 - 4,14 (m, 1H), 4,14 - 4,08 (m, 1H), 3,63 (s, 3H), 2,59 (s, 3H), 2,25 - 2,11 (m, 1H), 1,98 - 1,84 (m, 1H), 1,80 - 1,71 (m, 1H), 1,68 1,53 (m, 2H), 1,50 - 1,40 (m, 1H). ...ν’ Exemplo 505 2’-cloro-5’-metoxi-6-metil- N-{5-[(3R)-3metilmorfolin-4-il] [l,3]tiazol[5,4-d]pirimidin2-il} - [4,4 ’ -bipiridina] -3 carboxamida 12 95 3,18 512,1 / 514,1 B RMN Ή (500 MHz, DMSO-ώ) δ 12,90 (s, 1H), 8,83 (s, 1H), 8,78 (s, 1H), 8,16 (s, 1H), 7,56 (s, 1H), 7,45 (s, 1H), 4,66 4,60 (m, 1H), 4,24 (d, J = 11,9 Hz, 1H), 3,95 - 3,90 (m, 1H), 3,72 (d, J = 11,4 Hz, 1H), 3,62 (s, 3H), 3,61 - 3,57 (m, 1H), 3,47 - 3,40 (m, 1H), 3,20 (dd, J = 13,2; 3,3 Hz, 1H), 2,59 (s, 3H), 1,19 (d, J = 6,9 Hz, 3H).XÁ h3ct Example 515 2'-chloro-5'-methoxy-6-methyl- N-{5-[(3S)-3methylmorpholin-4-yl] [l,3]thiazol[5,4-d]pyrimidin2-yl} - [4,4 ' -bipyridine]-3 carboxamide 14 96 3.18 512.1 / 2. 514.1 B NMR Ή (500 MHz, DMSO-ώ) δ 12.91(s,1H), 8.82(s,1H), 8.80(s,1H), 8.17(s,1H), 7.57(s,1H), 7.46(s,1H), 4.63 (dd, J = 6.9; 2.9 Hz, 1H), 4.24 (dd, J = 13.6; 2.9 Hz, 1H), 3.93 (dd, J = 11.1, 3.7 Hz, 1H), 3.72 (d, J = 11.4 Hz, 1H), 3.62 (s, 3H), 3.61 - 3.57 (m, 1H), 3.44 (td, J = 11.4; 3.1 Hz, 1H), 3.23 - 3.16 (m, 1H), 2.60 (s, 3H), 1.20 (d, J = 6.7 Hz, 3H). χ nor if Ύ λ—n O 4 %NH 1 II II \=n )—ch3 h3C Λ9 H h3c n Example 525 2'-chloro-5'-methoxy-6-methylN- {5-[(propan-2-yl)amino][l,3]thiazol[5,4-d]pyrimidin2-yl} - [4,4 ' . -bipyridine]-3 carboxamide 3 97 2.07 470.3 / 472.3 B NMR Ή (500 MHz, DMSO-ώ) δ 12.83(s,1H), 8.84(s,1H), 8.65(s,1H), 8.16(s,1H), 7.53(s,1). 1H), 7.42 (s, 1H), 7.20 (s, 1H), 4.09 - 4.01 (m, 1H), 3.63 (s, 3H), 2.59 (s, 3H), 1.16 (d, J=6.6Hz, 6H). Petition 870250080361, dated 08 / 09 / 2025, pages 428 / 513 147 / 231 .N,,___„Cl h,c^ Ji J Αν vx, oon—5 / —NA, O 1 Ϊ Ϊ >=N VV v Λη SHC >N^ Example 531 2'-chloro-5'-methoxy-6-methyl- N-(5-{2-oxa-7azaspiro[3,5]nonan-7-yl}[1,3]thiazol[5,4-d]pyrimidin2-yl)-[4,4'-bipyridine]-3carboxamide 10 96 3.12 538.1 / 540.1 B 1H NMR (500 MHz, DMSO-d6) 12.86 (s, 1H), 8.86 (s, 1H), 8.67 (s, 1H), 8.15 (s, 1H), 7.52 (s, 1H), 7.39 (s, 1H), 4.35 (s, 4H), 3.74-3.67 (m, 4H), 3.62 (s, 3H), 2.58 (s, 3H), 1.85-1.76 (m, 4H) Intermediate 72 3-(2-{2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-amido}-[1,3]thiazol[5,4-d]pyrimidin-5-yl)-3,8-diazabicyclo[3.2.1]octano-8-carboxylate tert-butyl 96 88 1.08 623.3 / 625.3 A Intermediate 82 4-(2-{2'-chloro-5'-methoxy-6-methyl-[4,4' -bipyridine] -3 -amido} - [1,3]thiazol[5,4-d]pyrimidin-5-yl)piperazine-1-tert-butylcarboxylate 88 100 1.03 597.2 / 599.2 A Table 8 - Solvent and reaction temperature used in the preparation of Examples in Table 7 above. Footnote in Table x above: Reaction Solvent | Reaction Temperature (°C) | 1 Ethanol | 80 | 2 n-Butanol | 100 | 3 Ethanol / DCE | 80 | 4 n-Butanol | 80 | 5 n-Butanol | 110 General procedure E for Boc deprotection

[00317] A 4M hydrogen chloride solution in 1,4-dioxane (10 equiv.) was added to the required precursor with Boc-protected amine (derived from general method D, 1 equiv.) at room temperature. The mixture was stirred at room temperature and monitored by LCMS until the reaction Petition 870250080361, dated 08 / 09 / 2025, pages 429 / 513 148 / 231 was completed. The mixture was concentrated under reduced pressure and the residue purified by preparative HPLC method B to provide the desired products. Example 54 Synthesis of 2'-chloro-N-(5-{3,8-diazabicyclo[3.2.1]octan-3-yl}[1,3]thiazol[5,4-d]pyrimidin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3carboxamide Boc NH

[00318] 4M hydrogen chloride in 1,4-dioxane (250 pL, 1 mmol) was added 3-(2-{2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-amido}-[1,3]thiazol[5,4-d]pyrimidin-5-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate tert-butyl (200 mg, 0.1 mmol, Intermediate 7, prepared with general procedure D) and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated and the residue purified by preparative HPLC method B to give the title compound (15 mg, 30% yield) as a yellow powder. 1H NMR (400 MHz, DMSO-de) δ 8.93 (s, 1H), 8.56 (s, 1H), 8.13 (s, 1H), 7.44 (s, 1H), 7.29 (s, 1H), 4.26 (dd, J = 13.1; 2.4 Hz, 2H), 3.81 - 3.75 (m, 2H), 3.62 (s, 3H), 3.08 (dd, J = 13.0; 2.1 Hz, 2H), 2.56 (s, 3H), 1.83 1.61 (m, 4H), two interchangeable protons not observed. LCMS (method D); RT 1.83 minutes (99%), m / z 523.4 / 525.3 (M+H)+

[00319] Example 55 in Table 9 below was prepared using the general procedure E described above. Petition 870250080361, dated 08 / 09 / 2025, pages 430 / 513 149 / 231 Table 9 Example Yield LCMS Purity (%) LCMS RT (min.) m / z LCMS Method 1H NMR Example 55 2'-chloro-5'-methoxy-6-methyl- N-[5-(piperazin-1-yl)-[1,3]thiazol[5,4-d]pyrimidin2-yl]-[4,4'-bipyridine]-3-carboxamide 23 100 1.64 497.2 / 499.2 B 1H NMR (400 MHz, DMSO-de) δ 8.93 (s, 1H), 8.57 (s, 1H), 8.14 (s, 1H), 7.44 (s, 1H), 7.29 (s, 1H), 3.74 (t, J = 5.0 Hz, 4H), 3.62 (s, 3H), 2.90 (t, J = 5.1 Hz, 4H), 2.56 (s, 3H), two interchangeable protons not observed. Examples 56 and 57

[00320] Examples 56 and 57 in Table 10 below were prepared in the same manner as Example 36B above. Table 10 Example: LCMS Purity Yield (%) LCMS RT (min.) m / z LCMS Method 1H NMR ..JÇP! ' Example 56 2'-chloro-5'-methoxy-6-methyl- N-[6-(2-oxopyrrolidin-1-yl)1,3-benzothiazol-2-yl]-[4,4'bipyridine]-3-carboxamide 14 90 2.77 494.1 / 496.1 B 1H NMR (500 MHz, DMSO-de) δ 8.88 (s, 1H), 8.17 - 8.04 (m, 2H), 7.78 - 7.63 (m, 2H), 7.50 (s, 1H), 7.37 (s, 1H), 3.88 (t, J = 7.0 Hz, 2H), 3.59 (s, 3H), 2.58 (s, 3H), 2.08 (p, J = 7.6 Hz, 2H), a methylene signal obscured by the solvent peak and an unobserved exchangeable proton. .%xCi o JU ov \ i 1H (400 MHz, DMSO-de) δ 13.00 (s, 1H), 8.86 (s, 1H), 8.16 (s, 1H), 8.01 (d, J = 2.0 Hz, 1H), 7.80 (d, J = 8.6 Hz, 1H), 7.59 (s, 1H), 7.51 7.42 (m, 2H), 4.23 (s, 2H), 4.04 - 3.96 (m, 2H), 3.81 - 3.74 (m, 2H), 3.60 (s, 3H), 2.61 (s, 3H). General procedure F for Ullman coupling

[00321] A solution of the desired iodobenzothiazole (1 equiv.) in DMSO, the necessary amide was added (2 equiv.), cesium carbonate (3 Petition 870250080361, dated 08 / 09 / 2025, pages 431 / 513 150 / 231 equiv.) and copper(I) iodide (3 equiv.). The mixture was degassed under nitrogen and then 1,2-dimethylethylenediamine (3 equiv.) was added. The mixture was stirred at 100°C and monitored by LCMS until complete. The mixture was cooled to room temperature, diluted with DCM, and washed with saturated ammonium chloride solution, then with water. The organic phase was treated with SMOPEX™ scavenging resin. The resin was filtered and the filtrate concentrated under reduced pressure. The residue was purified by automated chromatography with Biotage Isolera™ to provide the desired products. Example 58 Synthesis of 2'-chloro-5'-methoxy-6-methyl-N-[6-(3-methyl-2oxoimidazolidin-1-yl)—1J3-benzothiazol-2-yl]-14,4'-bipyridine]-3-carboxamide H3C I N H H3C H3C CH3

[00322] To a solution of 2'-chloro-N-(6-iodo-1,3-benzothiazol-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide (Example 4, 100 mg, 0.17 mmol) in DMSO (2 mL), 1-methylimidazolidin-2-one (35 mg, 0.35 mmol), cesium carbonate (169 mg, 0.52 mmol) and copper(I) iodide (99 mg, 0.52 mmol) were added. The mixture was degassed under a stream of nitrogen, then 1,2-dimethylethylenediamine (56 pL, 0.52 mmol) was added and the mixture heated to 100°C for 2 hours. The reaction mixture was cooled to room temperature, diluted with DCM (25 mL), and sequentially washed with saturated ammonium chloride solution (20 mL then 2 x 10 mL), water (10 mL), and brine (10 mL). The organic phase was passed through a Telos™ phase separator, treated with SMOPEX™ metal scavenging resin, and stirred overnight. The solution was filtered and concentrated under reduced pressure.The crude residue was purified by automated chromatography with Biotage Isolera™ (C18 Duo, 12g) using a gradient of 100% acetonitrile in water (0.1% formic acid). The fractions that... Petition 870250080361, dated 08 / 09 / 2025, pages 432 / 513 Samples 151 / 231 containing the product were combined and further purified by automated chromatography with Biotage Isolera™ (Sfar Duo 10g) using a 0-10% methanol gradient in DCM to provide the title compound (8.7 mg, 10% yield) as a colorless powder. 1H NMR (500 MHz, DMSO) 7.44 (s, 1H) 3.92 - 3.79 (m, 2H), 3.60 (s, 3H), 3.51 - 3.41 (m, 2H), 2.78 (s, 3H), 2.59 (s, 3H). LCMS (method D); RT 1.57 minutes (99%), m / z 509.3 / 511.2 (M+H)+.

[00323] Examples 59 and 60 in Table 11 below were prepared using the general procedure F described above. Table 11 Exemplo Rendimento Pureza LCMS (%) LCMS RT (min.) m / z Método de LCMS RMN 1H , nx___„ao x0' o nA J AA N^U, AJl H h3c n Exemplo 59 2'-chloro-5'-metoxi-6-metil- N-[6-(2-oxo-1,3oxazolidin-3-il)-1,3benzotiazol-2-il]-[4,4'bipiridina] - 3-carboxamida 18 100 1.39 496.2 / 498.2 D RMN 1H (500 MHz DMSO-de) δ 12.92 (s, 1H), 8.85 (s, 1H), 8.15 (s, 1H), 8.08 (s, 1H), 7.84 7.68 (m, 2H), 7.57 (s, 1H), 7.45 (s, 1H), 4.53 4.39 (m, 2H), 4.22 - 4.06 (m, 2H), 3.60 (s, 3H), 2.60 (s, 3H). ,Ύ^α 0 H.c'Xr Exemplo 60 2'-chloro-5'-metoxi-6-methylN-[6-(2-oxoimidazolidin-1il)-1,3-benzotiazol-2-il][4,4'-bipiridina]-3carboxamida 12 100 2.39 495.1 / 497.0 B RMN 1H (400 MHz, DMSO) d 12.84 (s, 1H), 8.84 (s, 1H), 8.16 (s, 1H), 8.01 (s, 1H), 7.83-7.73 (m, 1H), 7.73-7.63 (m, 1H), 7.56 (s, 1H), 7.44 (s, 1H), 6.98 (s, 1H), 3,953.85 (m, 2H), 3.60 (s, 3H), 3.46-3.39 (m, 2H), 2.60 (s, 3H). Examples 61 to 75

[00324] Examples 61 to 75 listed in Table 12 below were prepared in a manner analogous to the general procedure C described previously. In parentheses, (1) indicates that the reaction was carried out at room temperature, (2) at 80°C, (3) at 90°C and (4) at 50°C. When the reactions Petition 870250080361, dated 08 / 09 / 2025, pages 433 / 513 152 / 231 were heated, the components were first mixed at room temperature. Table 12 Example: LCMS Purity Yield (%) LCMS Rt (min.) m / z LCMS Method RMN 1H Example 61 (2) 2'-chloro-5'-metoxi-6-methyl-N[6-(2-oxopiperidin-1-il)-[1,3]tiazol[4,5-c]piridin-2-il]-[4,4'-bipiridina]-3-carboxamide 15 100 2.64 509.4 / 507.4 B RMN 1H (400 MHz, DMSO-de) δ 13.16 (s, 1H), 8.89 (s, 2H), 8.16 (s, 2H), 7.58 (s, 1H), 7.46 (s, 1H), 3.88 - 3.81 (m, 2H), 3.61 (s, 3H), 2.61 (s, 3H), 2.46 - 2.43 (m, 2H), 1.92 - 1.83 (m, 4H). ... -3carboxamida 20 99 1.17 412.2 / 414.1 D RMN 1H (500 MHz, DMSO-de) δ 13.54 (s, 1H), 9.36 (s, 1H), 8.90 (s, 1H), 8.60 (d, J = 6.0 Hz, 1H), 8.50 (d, J = 5.9 Hz, 1H), 8.17 (s, 1H), 7.61 (s, 1H), 7.51 (s, 1H), 3.59 (s, 3H), 2.62 (s, 3H).Example 63 (1) 2'-chloro-N-{6-chloro[1,3]thiazol[5,4-c]pyridin-2-yl}5'-methoxy-6-methyl-[4,4'bipyridine] - 3-carboxamide 5 100 3.01 446.0 / 448.0 D 1H NMR (500 MHz, CDCl3) δ 8.83 (s, 1H), 8.79 (s, 1H), 8.07 (s, 1H), 7.24 (s, 1H), 7.09 (s, 1H), 6.57 (s, 1H), 3.70 (s, 3H), 2.69 (s, 3H). .yy B 1 Π J )=7 jy· 1 Example 64 (2) 2'-chloro-N-{6-chloro[1,3]thiazol[4,5-c]pyridin-2-yl}5'-methoxy-6-methyl-[4,4'bipyridine] - 3-carboxamide 83 100 3.12 446.0 / 448.0 B 1H NMR (500 MHz, DMSO-DE) 2.60 (s, 3H). Petition 870250080361, dated 08 / 09 / 2025, pages 434 / 513 153 / 231 - - 7^.1 Exemplo 65 (2) 2'-chloro-5'-methoxy-6-methyl-N[6-(morpholin-4-yl)- [1,3]thiazol[4,5-c]pyridin-2-yl][4,4'-bipyridine]-3- carboxamida 56 100 2,57 497,1 / 499,1 B NMR 1H (500 MHz, DMSO-de) δ 12.88 (s, 1H), 8.83 (s, 1H), 8.63 (s, 1H), 8.16 (s, 1H), 7.57 (s, 1H), 7.45 (s, 1H), 7.45 (s, 1H), 7.40 (s, 1H), 3.80 - 3.69 (m, 4H), 3.61 (s, 3H), 3.46 3.43 (m, 4H), 2.60 (s, 3H). H3C / ^y^l o-\,y ? HC Η^-'-ζ^ΗΚ-'^^^ CH3 NO Example 66 (1) 2'-chloro-N-[6(dimethylsulfamoyl)-1,3benzothiazol-2-yl]-5'-methoxy-6methyl-[4,4'-bipyridine]-3carboxamide 26 99 3.07 518.1 / 520.1 B 1H NMR (400 MHz, DMSO-de) δ 13.25 (s, 1H), 8.87 (s, 1H), 8.51 (d, J = 2.0 Hz, 1H), 8.17 (s, 1H), 7.96 (d, J = 8.6 Hz, 1H), 7.79 (d, J = 8.5 Hz, 1H), 7.60 (s, 1H), 7.48 (s, 1H), 3.60 (s, 3H), 2.63 (s, 6H), 2.61 (s, 3H). χ'τ- / '=vo.- Ύιιχ'-7 Exemplo 67 (2) 2'-chloro-5'-metoxi-6-metil-N- [6-(morfolin-4-il)- [1,3]tiazol[4,5-b]piridin-2-il][4,4'-bipiridina]-3- carboxamida 73 98 2.65 497.1 / 499.1 B RMN 1H (500 MHz, DMSO-de) δ 13.00 (s, 1H), 8.85 (s, 1H), 8.38 (d, J = 2.8 Hz, 1H), 8.16 (s, 1H), 7.97 (d, J = 2.8 Hz, 1H), 7.58 (s, 1H), 7,46 (s, 1H), 3.81 - 3.75 (m, 4H), 3.60 (s, 3H), 3.20 - 3.16 (m, 4H), 2.60 (s, 3H). VA Exemplo 68 (2) 2'-chloro-N-[6-(4hidroxipiperidin- 1-il)[1,3]tiazol[4,5-c]piridin-2-il]5'-metoxi-6-metil-[4,4'bipiridina]-3-carboxamida 11 100 2.05 511.2 / 513.2 B RMN 1H (500 MHz, DMSO-de) δ 12.82 (s, 1H), 8.83 (s, 1H), 8.58 (s, 1H), 8.16 (s, 1H), 7.56 (s, 1H), 7.45 (s, 1H), 7.38 (s, 1H), 4.48 (d, J = 4.3 Hz, 1H), 4.05 - 3.95 (m, 2H), 3.75 3.64 (m, 1H), 3.61 (s, 3H), 3.16 - 3.00 (m, 2H), 2.60 (s, 3H), 1.85 1.73 (m, 2H), 1.47 1.30 (m, 2H).Γ-- Nk H3C Jj ​​​​V-c1 O—X-ss / h3c^P HN-\>^ / Example 69 (1) N-(1,3-benzothiazol-2-yl)-2'chloro-5'-methoxy-6-methyl-[4,4'bipyridine]-3-carboxamide 17 100 2.22 411.1 / 413.1 F NMR 1H (600 MHz, DMSO-de) δ 12.92 (s, 1H), 8.85 (s, 1H), 8.15 (s, 1H), 7.97 (d, J = 7.9 Hz, 1H), 7.77 (d, J = 8.1Hz, 1H), 7.57 (s, 1H), 7.50 - 7.39 (m, 2H), 7.39 - 7.19 (m, 1H), 3.59 (s, 3H), 2.60 (s, 3H). Petition 870250080361, dated 09 / 08 / 2025, pp. 435 / 513 154 / 231 Exemplo 70 (2) 2'-chloro-5'-metoxi-6-metil-N[6-(2-oxopiperidin-1-il)- [1,3]tiazol[4,5-b]piridin-2-il][4,4'-bipiridina]-3carboxamida 72 98 2.57 509.1 / 511.1 B RMN 1H (500 MHz, DMSO-de) δ 13.25 (s, 1H), 8.88 (s, 1H), 8.48 (d, J = 2.5 Hz, 1H), 8.38 (d, J = 2.5 Hz, 1H), 8.16 (s, 1H), 7.60 (s, 1H), 7.47 (s, 1H), 3,68 (t, J = 5.7 Hz, 2H), 3.60 (s, 3H), 2.61 (s, 3H), 2.44 (t, J = 6.3 Hz, 2H), 1.93 - 1.85 (m, 4H). .. ί*Τ _ jy: Exemplo 71 (2) 2'-chloro-N-[6-(4- hydroxipiperidin- 1-il)- [1,3]tiazol[4,5-b]piridin-2-il]5'-metoxi-6-metil-[4,4'- bipiridina]-3-carboxamida 26 98 2,32 511.1 / 513.1 B RMN 1H (500 MHz, DMSO-de) δ 12.97 (s, 1H), 8.85 (s, 1H), 8.36 (d, J = 2.8 Hz, 1H), 8.17 (s, 1H), 7.95 (d, J = 2.8 Hz, 1H), 7.58 (s, 1H), 7,46 (s, 1H), 4.71 (d, J = 4.1 Hz, 1H), 3.69 - 3.63 (m, 1H), 3.61 (s, 3H), 3.59 - 3.52 (m, 2H), 2.93 - 2.90 (m, 2H), 2.61 (s, 3H), 1.88 - 1.82 (m, 2H), 1.56 - 1.49 (m, 2H). .<>o yy : ' Exemplo 72 (2) 2'-chloro-5'-metoxi-6-metil-N- [5-(morfolin-4-il)- [1,3]tiazol[5,4-b]piridin-2-il][4,4'-bipiridina]-3- carboxamida 25 100 2.82 497.1 / 499.1 B RMN 1H (500 MHz, DMSO-de) δ 8.84 (s, 1H), 8.15 (s, 1H), 7.87 (d, J = 9.0 Hz, 1H), 7.53 (s, 1H), 7.41 (s, 1H), 6.97 (d, J = 9.0 Hz, 1H), 3.74 - 3.69 (m, 4H), 3.61 (s, 3H), 3.49 - 3.44 (m, 4H), 2.59 (s, 3H). H,cA»n·^ Exemplo 73 (4) 2'-chloro-5'-metoxi-6-metil-N[5-(2-oxopiperidin-1-il)- [1,3]tiazol[5,4-b]piridin-2-il][4,4'-bipiridina]-3carboxamida 84 100 2.69 509.3 / 511.3 B RMN 1H (500 MHz, DMSO-de) δ 13.06 (s, 1H), 8.87 (s, 1H), 8.16 (s, 1H), 8.09 (d, J = 8.5 Hz, 1H), 7.70 (d, J = 8.8 Hz, 1H), 7.57 (s, 1H), 7,45 (s, 1H), 3.85 (t, J = 5.9 Hz, 2H), 3.61 (s, 3H), 2.60 (s, 3H), 2.48 2.45 (m, 2H), 1.93 1.78 (m, 4H). Petition 870250080361, on 09 / 08 / 2025, page. 436 / 513 155 / 231 Exemplo 74 (4) 2'-chloro-N-[5-(4- hydroxipiperidin- 1-il)- [1,3]tiazol[5,4-b]piridin-2-il]5'-metoxi-6-metil-[4,4'- bipiridina]-3-carboxamida 20 99 2.46 511.1 / 513.1 B RMN 1H (500 MHz, DMSO-de) δ 12.67 (s, 1H), 8.82 (s, 1H), 8.16 (s, 1H), 7.83 (d, J = 9.0 Hz, 1H), 7.55 (s, 1H), 7.43 (s, 1H), 6.98 (d, J = 9.1 Hz, 1H), 4.70 (d, J = 4.3 Hz, 1H), 4.07 - 3.96 (m, 2H), 3.75 - 3.65 (m, 1H), 3.62 (s, 3H), 3.19 - 3.05 (m, 2H), 2.59 (s, 3H), 1.86 - 1.74 (m, 2H), 1.44 - 1.30 (m, 2H). XVci c / 443.2 / 445.2 G RMN 1H (600 MHz, DMSO-de) δ 13.15 (s, 1H), 8.99 (s, 1H), 8.85 (s, 1H), 8.17 (s, 1H), 7.58 (s, 1H), 7.47 (s, 1H), 3.97 (s, 3H), 3.61 (s, 3H), 2.60 (s, 3H). Examples 76 to 82

[00325] Examples 76 to 82 in Table 13 below were prepared in a manner analogous to the general procedure D described previously. In parentheses, (1) indicates the use of nBuOH at 100°C and (2) the use of EtOH at 80°C. Table 13 Example Yield Purity LCMS (%) LCMS Rt (min.) m / z Method LCMS 1H NMR ..AJ1 ' Example 76 (2) 2'-chloro-5'-methoxy-6-methyl-N(5-{2-oxa-6-azaspiro[3,4]octan-6-yl}[1,3]thiazol[5,4-d]pyrimidin-2yl)-[4,4'-bipyridine]-3carboxamide 43 100 2.72 524.1 / 526.1 B 1H NMR (400 MHz, DMSO-de) δ 12.87 (s, 1H), 8.83 (s, 1H), 8.74 (s, 1H), 8.17 (s, 1H), 7.55 (s, 1H), 7.44 (s, 1H), 4.61 (d, J = 6.0 Hz, 2H), 4.51 (d, J = 6.0 Hz, 2H), 3.77 (s, 2H), 3.62 (s, 3H), 3.55 (d, J = 6.9 Hz, 2H), 2.59 (s, 3H), 2.25 (t, J = 7.0 Hz, 2H). Petition 870250080361, dated 09 / 08 / 2025, pp. 437 / 513 156 / 231 Exemplo 77 (1) 2’-cloro-N-{5-[(2-hidroxi-2metilpropil)amino]- [1,3]tiazol[5,4-d]pirimidin-2il}-5’-metoxi-6-metil-[4,4’bipiridina] - 3-carboxamida 31 100 2,54 500,1 / 502,1 B RMN 1H (400 MHz, DMSO-de) δ 12,85 (s, 1H), 8,82 (s, 1H), 8,67 (s, 1H), 8,17 (s, 1H), 7,56 (s, 1H), 7,44 (s, 1H), 6,97 (s, 1H), 4,52 (s, 1H), 3,63 (s, 3H), 2,59 (s, 3H), 1,12 (s, 6H). Exemplo 78 (1) 2’-cloro-5’-metoxi-6-metil-N{5-[(2-metilpropil)amino][1,3]tiazol[5,4-d]pirimidin-2il}-[4,4’-bipiridina] -3carboxamida 29 98 3,33 484,1 / 486,1 B RMN 1H (400 MHz, DMSO-de) δ 12,84 (s, 1H), 8,83 (s, 1H), 8,67 (s, 1H), 8,17 (s, 1H), 7,57 (s, 1H), 7,45 (s, 2H), 3,63 (s, 3H), 3,19 - 3,07 (m, 2H), 2,60 (s, 3H), 1,88 (hept, J = 6,6 Hz, 1H), 0,92 0,88 (m, 6H).Xaa Exemplo 79 (1) 2'-cloro-N-[5(ciclobutilamino)[1,3]tiazol[5,4-d]pirimidin-2il]-5'-metoxi-6-metil-[4,4'bipiridina] - 3-carboxamida 27 91 3,20 482,1 / ​​484,1 B RMN 1H (400 MHz, DMSO-de) δ 8.85 (s, 1H), 8.61 (s, 1H), 8.15 (s, 1H), 7.45 (s, 1H), 7.37 (s, 1H), 7.28 (br s, 1H), 4.42-4.36 (m, 1H), 3.67 (s, 3H), 2,60 (s, 3H), 2.31 - 2.24 (m, 2H), 2.04 - 1.96 (m, 2H), 1.72 - 1.64 (m, 2H). χο Exemplo 80 (2) 2'-chloro-5'-metoxi-N-[5-(4metoxipiperidin-1-il)-[1,3]tiazol[5,4-d]pirimidin-2il]-6-methyl-[4,4'-bipiridina]-3carboxamide 17 100 3,34 526,2 / 528,2 B RMN 1H (400 MHz, CDCl3) δ 10,47 (s, 1H), 8,81 (s, 1H), 8,10 - 7,95 (m, 2H), 7,20 7,13 (m, 2H), 4,36 4,24 (m, 2H), 3,74 (s, 3H), 3,52 - 3,41 (m, 3H), 3.40 (s, 3H), 2.67 (s, 3H), 2.00 - 1.90 (m, 2H), 1.65 - 1.58 (m, 2H). Petition 870250080361, on 09 / 08 / 2025, page. 438 / 513 157 / 231 ,--¾. λ Exemplo 81 (2) 2'-chloro-N-(5-{6-hidroxi-2azaspiro[3,3]heptan-2-il}[1,3]tiazol[5,4-d]pirimidin-2il)-5'-metoxi-6-metil-[4,4'bipiridina] - 3-carboxamida 38 100 1,22 524.3 / 526.3 B RMN 1H (500MHz, DMSO-de) δ 12.90 (s, 1H), 8.84 (s, 1H), 8.71 (s, 1H), 8.17 (s, 1H), 7.55 (s, 1H), 7.44 (s, 1H), 5.06 (d, J = 6.2 Hz, 1H), 4.08 - 3.98 (m, 5H), 3.62 (s, 3H), 2.60 (s, 3H), 2.05 1.99 (m, 2H). Example 82(2) 2'-chloro-5'-metoxi-6-methyl-N(5-{6-oxa-2azaspiro[3,4]octan-2-il}[1,3]tiazol[5,4-d]pirimidin-2il)-[4,4'-bipiridina]-3carboxamide 8 100 2.77 524.1 / 526.1 B RMN 1H (400 MHz, CDCl3) δ 8.84 (s, 1H), 8.04 (s, 1H), 7.19 (s, 1H), 7.16 (s, 1H), 4.17 (s, 4H), 3.94 (s, 2H), 3.90 (t, J = 7.0 Hz, 3H), 3.74 (s, 3H), 2.69 (s, 3H), 2.23 (t, J = 7.0 Hz, 2H). Exemplo 83 Esquema 1 person de exemplo 83 PhI(OAc)2(NH4)2CO3 MeOH, RT Example 43 Exemplo 83 Example 83 - 2'-chloro-N-{6-[imino(methyl)oxo-À6-sulfanyl]-1,3-benzothiazol-2yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide

[00326] 2'-chloro-5'-methoxy-6-methyl-N-[6-(methylsulfanyl)-1,3-benzothiazol-l-2-yl]-[4,4'-bipyridine]-3-carboxamide (Example 43, 170 mg, 0.37 mmol) was dissolved in methanol (5.7 mL) and the mixture purged with N2(g). To the stirred mixture, ammonium carbonate (54 mg, 0.56 mmol) in methanol (2.8 mL) was added followed by diacetoxy-iodobenzene (275 mg, 0.85 mmol) in Petition 870250080361, dated 08 / 09 / 2025, pages 439 / 513 158 / 231 methanol (2.8 mL). The mixture was stirred at room temperature under N2(g) for 18 hours. The mixture was filtered and the filtrate concentrated under reduced pressure. The residue was purified by automatic chromatography with Biotage Isolera™ (Sfar Duo 10 g) using a 0-10% methanol gradient in DCM. The partially purified product was further purified by automatic chromatography with Biotage Isolera™ (C18 Duo, 12 g) using a 0-100% acetonitrile gradient in water (0.1% formic acid) to give the title compound (16 mg, 9%) as a colorless powder. 1H NMR (500 MHz, DMSO-de) δ 13.19 (s, 1H), 8.89 (s, 1H), 8.58 (s, 1H), 8.16 (s, 1H), 7.96 (d, J = 7.9 Hz, 1H), 7.90 (d, J = 8.2 Hz, 1H), 7.58 (s, 1H), 7.46 (s, 1H), 4.22 (s, 1H), 3.59 (s, 3H), 3.10 (s, 3H), 2.60 (s, 3H). LCMS (method B); Rt 2.24 minutes (100%), m / z 488.1 / 490.0 (M+H)+ General Procedure G for Ullman Coupling (described previously)

[00327] To a solution of the desired iodobenzothiazole (1 equiv.) in DMSO, the required amide (2 equiv.), cesium carbonate (3 equiv.) and copper(I) iodide (3 equiv.) were added. The mixture was degassed under N2(g) and then 1,2-dimethylethylenediamine (3 equiv.) was added. The mixture was heated to 100°C and monitored by LCMS until complete. The mixture was cooled to room temperature, diluted with DCM and washed with saturated ammonium chloride solution and water. The organic extracts were combined and treated with SMOPEX™ scavenging resin. The resin was filtered and the filtrate concentrated under reduced pressure. The residue was purified by automated chromatography with Biotage Isolera™ to provide the desired coupling products.

[00328] The following examples, in Table 14 below, were prepared in a similar manner: Petition 870250080361, dated 08 / 09 / 2025, pages 440 / 513 159 / 231 Table 14 Exemplo Rendimento Pureza LCMS (%) LCMS Rt (min.) m / z Método de LCMS RMN 1H Exemplo 84 2’-cloro-N-[6-(l,l-dioxolL6,2-tiazolidin-2-il)-l,3benzotiazol-2-il]-5 ’ -metoxi6-metil- [4,4 ’ -bipiridina] -3carboxamida 9 99 2,84 530,1 / 532,1 B RMN Ή (500 MHz, DMSO-X) δ 12,93 (s, 1H), 8,88 (s, 1H), 8,14 (s, 1H), 7,76 (s, 1H), 7,74 7,68 (m, 1H), 7,53 (s, 1H), 7,41 (s, 1H), 7,38 7,33 (m, 1H), 3,78 (t, J = 6,5 Hz, 2H), 3,60 (s, 3H), 3,51 (t, J = 7,5 Hz, 2H), 2,59 (s, 3H), 2,46 - 2,39 (m, 2H). III χ / '—' Exemplo 85 2’-cloro-N-{6-[(4R)-4hidroxi-2-oxopiperidin-1 - il] -1,3 -benzotiazol-2-il}-5 ’ metoxi-6-metil-[4,4’bipiridina] - 3-carboxamida 3 97 2,29 524,1 / 526,1 B RMN Ή (400 MHz, CDC13) δ 12,15 (s, 1H), 8,75 (s, 1H), 8,01 (s, 1H), 7,67 (d, J = 2,0 Hz, 1H), 7,13 (s, 1H), 7,09 - 7,01 (m, 2H), 6,91 - 6,80 (m, 1H), 4,43 - 4,34 (m, 1H), 3,98 - 3,87 (m, 1H), 3,65 (s, 3H), 3,62 - 3,52 (m, 1H), 2,82 (dd, J = 17,6; 4,5 Hz, 1H), 2,64 - 2,56 (m, 4H), 2,21 - 2,01 (m, 2H).86 δ 12.96 (s, 1H), 8.86 (s, 1H), 8.16 (s, 1H), 7.95 (d, J = 1.1 Hz, 1H), 7.77 (d, J = 8.6 Hz, 1H), 7.59 (s, 1H), 7.47 (s, 1H), 7.39 (dd, J=8.6, 2.2Hz, 1H), 3.72 - 3.67 (m, 2H), 3.60 (s, 3H), 3.14 (s, 2H), 2.79 - 2.72 (m, 2H), 2.61 (s, 3H), 2.31 (s, 3H). Example 87 Scheme 2 Summary of Example 87 Petition 870250080361, dated 09 / 08 / 2025, pp. 441 / 513 160 / 231 I * I·,··, I·. 1,4-dioxane-water 100°C Intermediate I1 - N-{5-chloro-[1,3]thiazol[5,4-d]pyrimidin-2-yl}carbamate tert-butyl Boc^ H

[00329] 5-chloro-[1,3]thiazol[5,4-d]pyrimidin-2-amine (1.53 g, 8.2 mmol), DMAP (200 mg, 1.64 mmol) and Et3N (1.14 mL, 8.2 mmol) in 2-Methyl THF (120 mL) were portion-by-portion treated with tert-butyl-carbonate tert-butoxycarbonyl (3.65 g, 16.4 mmol). The reaction was stirred at room temperature for 3 days, then concentrated under reduced pressure. The resulting solid was triturated with n-heptane (30 mL) and the resulting solid filtered and vacuum dried to give the title compound (2.42 g, 93%) as a white powder. LCMS (method H); Rt 1.68 minute (90%), m / z 231.1 (M-tbu)+ Intermediate J2^52(3J62dihydro-2H-pyran-42yl)2[1J3]thiazol[5J42dlpyrimidin222 amine h2n

[00330] A stirred suspension of tert-butyl N-(5-chlorothiazol[5,4-d]pyrimidin-2yl)carbamate (intermediate I1, 200 mg, 0.670 mmol), 2-(3,6dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolan (296 mg, 1.34 Petition 870250080361, dated 09 / 08 / 2025, pp. 442 / 513 A mixture of 161 / 231 mmol) and 2M K2CÜ3(aq) (1.0 mL, 2.01 mmol) in 1,4-dioxane (8 mL) and water (1.5 mL) was degassed under N2(g) for 5 minutes. SPhos (56 mg, 0.134 mmol) and Pd2(dba)3 (65 mg, 0.067 mmol) were added and the mixture stirred at 100°C overnight in a sealed pressure vessel. The mixture was cooled to room temperature and separated between water and EtÜAc. The layers were separated, and the aqueous layer was further extracted with EtÜAc (x 2). The combined organic layers were dried with hydrophobic filter paper and concentrated under reduced pressure. Reversed-phase column chromatography (30 g, Redisep gold C18 aq., 100% acetonitrile in water, neutral) yielded the title compound (64 mg, 41%) as a whitish solid. 1H NMR (500 MHz, DMSÜ-de) δ 8.59 (s, 1H), 8.10 (s, 2H), 7.06 - 7.05 (m, 1H), 4.30 - 4.28 (m, 2H), 3.81 (t, J = 5.5 Hz, 2H), 2.59 - 2.56 (m, 2H). LCMS (method E); Rt 0.54 minute (100%), m / z 235.2 (M+H)+ Example 87 - 2'-chloro-N-[5-(3,6-dihydro-2H-pyran-4-yl)-[1,3]thiazol[5,4d]pyrimidin-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide

[00331] Prepared analogously to the general procedure C at 90°C, followed by reversed-phase column chromatography (30 g, Redisep Aq18, 0-100% acetonitrile in water, neutral), then trituration with methanol to give the title compound (70 mg, 47%) as a white powder. 1H NMR (600 MHz, DMSÜ-de) δ 13.30 (s, 1H), 9.16 (s, 1H), 8.86 (s, 1H), 8.17 (s, 1H), 7.59 (s, 1H), 7.48 (s, 1H), 7.25 - 7.24 (m, 1H), 4.32 (br d, 2H, J = 2.8 Hz), 3.83 (s, 2H), 3.61 (s, 3H), 2.61 (s, 5H). LCMS (method G); Rt 2.19 minutes (97%), m / z 495.1 / 497.1 (M+H)+ Example 88 Petition 870250080361, dated 09 / 08 / 2025, pp. 443 / 513 162 / 231 Scheme 3 Summary of Example 88 cat., 80 °C amine, n-buOH 100 °C Intermediate 13 - 5-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2(trifluoromethyl)pyridine

[00332] Di-Mp-methanol-di-iridium(Ir-Ir)-cyclo-octa-1,5-diene (1:2) (37 mg, 0.057 mmol) and 4- / erc-butyl-2-(4-tert-butyl-2-pyridyl)pyridine (30 mg, 0.113 mmol) were added to a Schlenk flask that had been emptied and refilled with N2(g) three times. 4,4,5,5-tetramethyl-1,3,2-dioxaborolan (1.23 mL, 8.47 mmol) and 5-methoxy-2-(trifluoromethyl)pyridine (0.79 mL, 5.65 mmol) were added via syringe. The flask was closed and the mixture was heated to 80°C for 2 hours. The mixture was cooled to room temperature and diluted with EtOAc. The resulting mixture was concentrated under reduced pressure. The crude product thus obtained was Petition 870250080361, dated 09 / 08 / 2025, pp. 444 / 513 163 / 231 purified by column chromatography (SiO2, 40 g Redisep gold, 0-100% EtOAc-EtOH (3:1) in heptane) to give the title compound (1.66 g, 81%), a beige-colored solid. 1H NMR (400 MHz, DMSO-d) δ 8.56 (s, 1H), 7.80 (d, J = 0.6 Hz, 1H), 3.98 (s, 3H), 1.31 (s, 12H). LCMS (method F); Rt 0.93 minute (94%), m / z 222.2. Intermediate I4 - 5'-methoxy-6-methyl-2'-(trifluoromethyl)-[4,4'-bipyridine]-3-methylcarboxylate

[00333] In a sealed flask, a stirred suspension of 5-methoxy-4(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)pyridine (intermediate I3, 640 mg, 1.82 mmol), methyl 4-bromo-6-methylpyridine-3-carboxylate (220 mg, 0.956 mmol) and K2CO3 (396 mg, 2.87 mmol) in 1,4-dioxane (17.2 mL) and water (5.0 mL) was degassed over N2(g) for 5 minutes. Palladium dichloride DTBPF (125 mg, 0.191 mmol) was added and the mixture was stirred at 100°C for 3 hours. The mixture was cooled to room temperature and diluted with water and EtOAc. The organic layer was washed with brine, dried with hydrophobic filter paper, then concentrated under reduced pressure. Reversed-phase column chromatography (0-100% ACN in water, redisep C18 aq. 50 g) yielded the title compound (316 mg, 96%) as a brown gum. LCMS (method F); Rt 1.23 minute (94%), m / z 327.3 (M+H)+. Intermediate I5 - 5'-methoxy-6-methyl-2'-(trifluoromethyl)-[4,4'-bipyridine]-3-carboxylic acid Petition 870250080361, dated 08 / 09 / 2025, pages 445 / 513 164 / 231

[00334] Prepared analogously to general procedure B with intermediate I4 providing the title compound (300 mg, quantitative) as a brown foam. 1H NMR (500 MHz, DMSO-d 6) δ 12.3 - 13.5 (m, 1H), 8.92 (s, 1H), 8.59 (s, 1H), 7.81 (s, 1H), 7.34 (s, 1H), 3.90 (s, 3H), 2.57 (s, 3H). LCMS (method F); Rt 0.91 minute (96%), m / z 313.2 (M+H)+. Intermediate I6 - 1-{2-amino-[1,3]thiazol[5,4-d]pyrimidin-5-yl}piperidin-4-ol

[00335] Piperidin-4-ol (130 mg, 1.29 mmol) was added to a suspension of 5-chlorothiazol[5,4-d]pyrimidin-2-amine (50 mg, 0.26 mmol) in n-butanol (1.3 mL). The reaction was stirred at 100°C overnight. After cooling to room temperature, the mixture was diluted with EtOAc and washed with water followed by brine. The organic phase was dried (Na2SO4) and concentrated under reduced pressure to provide an orange-colored solid. The solid was evaporated along with diethyl ether to remove residual n-butanol, and the resulting solid was triturated with diethyl ether and filtered under vacuum. The filtered cake was dried under a stream of N2(g) to provide the title compound (56 mg, 82%) as an orange-colored powder. 1H NMR (500 MHz, DMSOd6) δ 8.25 (s, 1H), 7.48 (s, 2H), 4.68 (d, J = 4.3 Hz, 1H), 4.19 (dt, J = 12.7; 4.4 Hz, 2H), 3.73 - 3.66 (m, 1H), 3.21 - 3.15 (m, 2H), 1.78 - 1.72 (m, 2H), Petition 870250080361, dated 08 / 09 / 2025, pages 446 / 513 165 / 231 1.35 - 1.27 (m, 2H)-.LCMS (Method A); Rt 0.43 minute (100%), m / z 252.1 (M+H)+ Example 88 - N-[5-(4-hydroxypiperidin-1-yl)-[1,3]thiazol[5,4-d]pyrimidin-2-yl]^-methoxy-o-methyl-r-^rifluoromethylHylj^bipyridin^^ F H3C H3C OH

[00336] Prepared analogously to general procedure C with intermediates I5 and I6 at 80°C. Purified by reverse-phase chromatography (30 g Redisep Aq18) using an acetonitrile-in-water gradient from 0% to 100% (neutral) to give the title compound (23 mg, 28%) as a brown powder. 1H NMR (600 MHz, DMSO-d) δ 12.89 (s, 1H), 8.84 (s, 1H), 8.74 (s, 1H), 8.54 (s, 1H), 7.94 (s, 1H), 7.51 (s, 1H), 4.72 (d, J = 4.25 Hz, 1H), 4.27 (dt, J = 13.3; 4.6 Hz, 2H), 3.71 - 3.76 (m, 4H), 3.29 - 3.30 (m, 2H), 2.61 (s, 3H), 1.75 - 1.82 (m, 2H), 1.31 - 1.38 (m, 2H). LCMS (method G); Rt 1.9 minutes (99%), m / z 546.3 (M+H)+ Example 89 Scheme 4 Summary of Example 89 Ag Pd2(dba)3, DPEPos, PhMe, 80 °C Example 89 - N-[5-(4-hydroxypiperidin-1-yl)-[1,3]thiazol[5,4-d]pyrimidin-2-yl]52-methoxy-6-methyl-2'-(trifluoromethyl)-[4,4'-bipyridine]-3.-carboxamide Petition 870250080361, dated 08 / 09 / 2025, pages 447 / 513 166 / 231

[00337] To a stirred solution of 4-(2-chloro-5-methoxy-4-pyridyl)-6-methyl-N-(5-morpholinothiazol[5,4-d]pyrimidin-2-yl)pyridine-3-carboxamide (Example 22, 70 mg, 0.141 mmol) in anhydrous toluene (1.8 mL, degassed for 10 minutes under N2(g) spray before use) under N2(g), Pd2(dba)3 (13 mg, 0.01 mmol) and DPEPhos (15 mg, 0.028 mmol) were added, followed by [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-1-io2-yl]-(difluoromethyl)silver (100 mg, 0.183 mmol). The mixture was stirred at 80°C for 18 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure and the gum was then purified by normal-phase column chromatography (10 g sfar, 0-100% EtOAc in heptane, then 0-20% methanol in EtOAc).The partially purified product was further purified by preparative HPLC (method C) under the following conditions: Column: Sunfire C18, 150 x 19 mm, 5 µm; flow rate: 20 mL / min, 595% formic acid 0.1% in acetonitrile - formic acid 0.1% in water over 18 minutes. This yielded the title compound (4 mg, 6%), after lyophilization from acetonitrile-water 1:1, as a whitish solid. 1H NMR (500 MHz, DMSO-de) δ 8.99 (s, 1H), 8.47 (s, 1H), 8.41 (s, 1H), 8.29 (s, 1H), 7.55 (s, 1H), 7.21 (s, 1H), 6.95 (t, J = 55.2 Hz, 1H), 3.70 (s, 3H), 3.68 - 3.61 (m, 8H), 2.54 (s, 3H). LCMS (Method B); Rt 2.79 minutes (94%), m / z 514.1 (M+H)+. Example 90 Scheme 5 Example Summary 90 Petition 870250080361, dated 09 / 08 / 2025, pp. 448 / 513 167 / 231 Intermediate I11 - 4-bromo-2-(trifluoromethyl)pyrimidin-5-amine

[00338] To a stirred solution of 2-(trifluoromethyl)pyrimidin-5-amine (500 mg, 2.91 mmol) in anhydrous acetonitrile (5 mL), 1-bromopyrrolidine-2,5-dione (628 mg, 3.49 mmol) was added in portions. The mixture was stirred at room temperature for 17 hours. Under stirring, the mixture was poured into a solution of 1N Na2S2O3(aq) and EtOAc. The organic layer was dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by normal-phase chromatography (SiO2, Biotage, Redisep 24 g) using a 70-100% DCM gradient on heptane to give the title compound (266 mg, 38%) as an orange powder. 1H NMR (600 MHz, DMSO-άβ,) δ 8.22 (s, 1H), 6.63 (s, 2H). Intermediate I12 - 5-(trifluoromethyl)-[1,3]thiazol[5,4-d]pyrimidin-2-amine

[00339] To a stirred suspension of potassium thiocyanate (120 mg, 1.17 mmol) in acetic acid (1.5 mL), 4-bromo-2 was added. Petition 870250080361, dated 08 / 09 / 2025, pages 449 / 513 168 / 231 (trifluoromethyl)pyrimidin-5-amine (Intermediate I11, 257 mg, 1.06 mmol). The mixture was stirred at 80°C overnight. The mixture was poured into diethyl ether, the resulting solid was filtered, the filtrate treated with water and 17 ml of 2 M NaOH(aq) were added. The organic layer was dried with Na2SO4 then concentrated to dryness. The residue was ground with DCM, filtered, rinsed several times with n-pentane and dried under vacuum at 50°C overnight to give the title compound (146 mg, 62%) as a beige powder. 1H NMR (600 MHz, DMSO-de) δ 8.76 (s, 1H), 8.56 (s, 2H). LCMS (method E); Rt 0.64 minute (99%), m / z 221.1 (M+H)+ Example_____90_____-_____22-chlorio252-methoxy-6-methyl-N.[5.-(jrfluoI^ [1,3]thiazole [5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide

[00340] Prepared analogously to the general procedure C at 80°C, yielding the title compound (33 mg, 16%) as a white powder. 1H NMR (600 MHz, DMSO-de) δ 13.65 (br s, 1H), 9.39 (s, 1H), 8.89 (s, 1H), 8.17 (s, 1H), 7.61 (s, 1H), 7.50 (s, 1H), 3.60 (s, 3H), 2.61 (s, 3H). LCMS (method F); Rt 1.51 minute (100%), m / z 481.1 / 482.9 (M+H)+ Example 91 Scheme 6 Summary of Example 91 Intermediate_17^_5-methi]-[1J3Jthiazol£5J42dJ,pyrimidin-22amine Petition 870250080361, dated 08 / 09 / 2025, pages 450 / 513 169 / 231 h2n

[00341] Prepared analogously to intermediate I12, using the corresponding commercial aryl chloride as starting material. 1H NMR (500 MHz, DMSO-de) δ 8.51 (s, 1H), 8.00 (s, 2H), 2.58 (s, 3H). Example 91 - 2'-chloro-5'-methoxy-6-methyl-N-{5-methyl-[1,3]thiazol[5,4d]pyrimidin-2-yl}-[4,4'-bipyridine]-3-carboxamide

[00342] Prepared analogously to the general procedure C at 80°C. The mixture contained a precipitate which was filtered and washed sequentially with water and acetonitrile to give a white solid. Purification by reversed-phase column chromatography (10-100% acetonitrile in water, AcOH 0.1%) to give the title compound (100 mg, 39%) as a white solid. 1H NMR (400 MHz, DMSO-de) δ 13.26 (s, 1H), 9.08 (s, 1H), 8.86 (s, 1H), 8.17 (s, 1H), 7.59 (s, 1H), 7.48 (s, 1H), 3.61 (s, 3H), 2.72 (s, 3H), 2.61 (s, 3H). LCMS (method G); Rt 1.86 minutes (100%), m / z 427.1 / 429.1 (M+H)+ Example 92 Scheme 7 Summary of Example 92 Petition 870250080361, dated 08 / 09 / 2025, pages 451 / 513 170 / 231 CH3 Example 92 - 5'-methoxy-2',6-dimethyl-N-[5-(morpholin-4-yl)-[1,31thiazol[5,4dlpyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide

[00343] 4-(2-chloro-5-methoxy-4-pyridyl)-6-methyl-N-(5-morpholinothiazol[5,4-d]pyrimidin-2-yl)pyridine-3-carboxamide (Example 22, 120 mg, 0.241 mmol), trimethylboroxine (121 mg, 0.964 mmol) and CS2CO2 (236 mg, 0.723 mmol) were stirred in 1,4-dioxane (0.66 mL) and water (0.28 mL) and the mixture degassed under N2(g) spray for 5 minutes. Pd(dppf)Cl2.DCM (20 mg, 0.0241 mmol) was added and the mixture further degassed under N2(g) for 5 minutes. The mixture was stirred at 100°C (in a pressure flask) for 18 hours. After being cooled to room temperature, the mixture was further treated with trimethylboroxine (121 mg, 0.964 mmol), Cs2CO2 (236 mg, 0.723 mmol) and Pd(dppf)Cl2.DCM (20 mg, 0.0241 mmol). The mixture was degassed for 5 minutes under N2(g) spray and then stirred at 100°C for 6 hours. After being cooled to room temperature, the mixture was diluted with DCM (6 mL), at which point a precipitate formed.The mixture was filtered and the filtered cake washed with DCM. The filtrate was treated as follows. The organic phase was separated and concentrated under reduced pressure. The residue was dissolved in DMSO (2.5 mL with 1 drop of water). Preparative HPLC (method A), followed by lyophilization from acetonitrile / water, yielded the partially purified product. Normal phase column chromatography (0-10% MeOH in...) Petition 870250080361, dated 08 / 09 / 2025, pages 452 / 513 171 / 231 DCM), followed by lyophilization from acetonitrile / water, yielded the title compound (24 mg, 20%) as a whitish powder. Ή NMR (400 MHz, CDC13) 10.18 - 9.99 (m, 1H), 8.75 (s, 1H), 8.17 - 8.08 (m, 2H), 7.09 (s, 1H), 6.94 (s, 1H), 3.79 - 3.70 (m, 8H), 3.69 (s, 3H), 2.60 (s, 3H), 2.48 (s, 3H). LCMS (method B); Rt 1.89 minute (100%), m / z 478.1 (M+H)+ Example 93 Scheme 8 Example Summary 93 TCFH, NMI MeCN, 90 °C amine, EtOH, 110°C (sealed tube) Intermediate 18 - 2'-fluoro-5'-methoxy-6-methyl-[4,4'-bipyridine-1,3-carboxylate]

[00344] Prepared analogously to general procedure A, providing the title compound (296 mg, 65%) as a light yellow oil. NMR Ή (400 MHz, DMSO-^) δ 8.88 (s, 1H), 7.97 (d, J = 1.9 Hz, 1H), 7.37 (s, 1H), 7.22 (d, J = 2.9 Hz, 1H), 3.75 (s, 3H), 3.67 (s, 3H), 2.58 (s, 3H). Petition 870250080361, dated 08 / 09 / 2025, pages 453 / 513 172 / 231 LCMS (method F); Rt 0.96 minute (98%), m / z 277.2 (M+H)+ Intermediate I9 - 2'-fluoro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylate sodium

[00345] To a stirred solution of methyl 4-(2-fluoro-5-methoxy-4-pyridyl)-6-methylpyridine-3-carboxylate (intermediate I8, 296 mg, 1.05 mmol) in methanol (3 mL), 1 M NaOH(aq) (3.0 mL, 3.0 mmol) was added at room temperature. The mixture was stirred for 2 hours at room temperature and concentrated under reduced pressure to give the title compound (406 mg, 95%) as a yellow solid. 1H NMR (400 MHz, DMSO-d 6) δ 8.73 (s, 1H), 7.83 (d, J = 1.8 Hz, 1H), 6.94 (s, 1H), 6.87 (d, J = 2.8 Hz, 1H), 3.72 (s, 3H), 2.44 (s, 3H).LCMS (method F); Rt 0.72 minute (97%), m / z (free acid) 263.3 (M+H)+ Intermediate I10 - 5-(morpholin-4-yl)-[1,3]thiazol[5,4-d]pyrimidin-2-amine

[00346] To a suspension of 5-chloro-[1,3]thiazol[5,4-d]pyrimidin-2amine (2.25 g, 11.5 mmol) in ethanol (43 mL) at room temperature, morpholine (9.88 mL, 115 mmol) was added. The flask was sealed and the mixture was stirred at 110°C for 6 hours. The mixture was allowed to cool to room temperature and stirred at room temperature overnight. The precipitate was filtered, washed with ethanol (x2), diethyl ether (x3) and vacuum dried overnight to give a pink powder. This was triturated with water (x3), filtered and vacuum dried at 45°C to give the title compound. Petition 870250080361, dated 08 / 09 / 2025, pages 454 / 513 173 / 231 (1.27 g, 47%) as a pinkish powder. NMR Ή (400 MHz, DMSO-1 / 6) δ 8.29 (s, 1H), 7.54 (s, 2H), 3.75 - 3.51 (m, 8H). LCMS (method E); Rt 0.55 minute (95%), m / z 238.2 (M+H)+ Example 93 - 2'-fluoro-5'-methoxy-6-methyl-N-[5-(morpholin-4-yl)[1,31-thiazol[5,4-d1-pyrimidin-2-yl1-[4,4'-bipyridine]-3-carboxamide

[00347] Prepared analogously to the general procedure C at 90°C, followed by column chromatography (S1O2, 0-100% EtOAc / EtOH (3 / 1) in heptane) to give the title compound (94 mg, 47%) as a white solid. NMR Ή (400 MHz, DMSO-tZa) δ 12.93 (s, 1H), 8.84 (s, 1H), 8.80 (s, 1H), 7.92 (d, J= 1.6 Hz, 1H), 7.45 (s, 1H), 7.30 (d, J= 2.7 Hz, 1H), 3.77 - 3.64 (m, 8H), 3.60 (s, 3H), 2.61 (s, 3H). LCMS (method F); Rt 1.23 minutes (100%), m / z 482.3 (M+H)+ Example 94 Scheme 9 Example Summary 94 Intermediate 113 - N-[5-(2-oxopiperidin-1-iD-[1,31thiazol[5,4-d]pyrimidin-2yl] tert-butyl carbamate Petition 870250080361, dated 09 / 08 / 2025, pp. 455 / 513 174 / 231

[00348] tert-butyl N-(5-chlorothiazol[5,4-d]pyrimidin-2-yl)carbamate (intermediate I1, 750 mg, 2.48 mmol), piperidin-2-one (493 mg, 4.97 mmol) and CS2CO3 (2.89 g, 8.70 mmol) were stirred in anhydrous 1,4-dioxane (28 mL) and degassed by spraying with N2(g) for 10 minutes. Pd2(dba)3 (228 mg, 0.248 mmol) and Xantphos (288 mg, 0.497 mmol) were added and the mixture was further degassed by spraying with N2(g) for 5 minutes. The mixture was stirred at 105°C under N2(g) for 18 hours. After cooling to room temperature, the mixture was diluted with water (6 mL) and EtOAc (20 mL). The organic phase was separated and the aqueous phase was further extracted with EtOAc (2 x 20 mL). The combined organic layers were washed with brine (20 mL). The aqueous phase was extracted with EtOAc (2 x 20 mL) and the combined organic layers were dried (MgSO4) and then concentrated under reduced pressure. Column chromatography (0-10% methanol in DCM) yielded the title compound (812 mg, 61%).1H NMR (400 MHz, DMSO-d6) δ 12.27 (s, 1H), 9.05 (s, 1H), 3.77 (t, J = 5.6 Hz, 2H), 2.44 (t, J = 6.2 Hz, 2H), 1.95 - 1.80 (m, 4H), 1.53 (s, 9H). LCMS (method A); Rt 0.76 minute (96%), m / z 350.1 (M+H)+. Intermediate I14 - 1-{2-amino-[1,3]thiazol[5,4-d]pyrimidin-5-ilipipendin-^one hydrochloride

[00349] N-[5-(2-oxo-1-piperidyl)thiazol[5,4-d]pyrimidin-2-yl]carbamate tert-butyl (intermediate I13 390 mg, 0.726 mmol) was stirred with 4 M HCl in 1,4-dioxane (5.0 mL, 20.0 mmol) for 1 hour at room temperature. The mixture was diluted with anhydrous 1,4-dioxane (5 mL) and stirred for 24 hours. Petition 870250080361, dated 09 / 08 / 2025, pp. 456 / 513 175 / 231 The reaction was concentrated under reduced pressure and evaporated sequentially along with acetonitrile (10 mL) and heptane (10 mL) to give the title compound (406 mg, 92%). 1H NMR (400 MHz, DMSO-de) δ 8.58 (s, 1H), 7.62 - 7.24 (m, 3H), 3.69 (t, J = 5.6 Hz, 2H), 2.40 (t, J = 6.3 Hz, 2H), 1.91 - 1.78 (m, 4H). LCMS (method A); Rt 0.43 minute (86%), m / z 250.0 (M+H)+ Example 94 - 2'-chloro-5'-methoxy-6-methyl-N-[5-(2-oxopiperidin-1-yl)[1,3]thiazol [5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide

[00350] Prepared analogously to the general procedure C at 80°C to give the title compound (23 mg, 13%) as a whitish solid. 1H NMR (400 MHz, CDCl3) δ 10.34 (s, 1H), 8.94 (s, 1H), 8.74 (s, 1H), 8.05 (s, 1H), 7.29 (s, 1H), 7.20 (s, 1H), 3.92 (t, J = 5.6 Hz, 2H), 3.75 (s, 3H), 2.71 (s, 3H), 2.60 (t, J = 6.4 Hz, 2H), 2.06 - 1.92 (m, 4H). LCMS (method B); Rt 2.58 minutes (99%), m / z 510.2 / 512.1 (M+H)+. Biological assay 1

[00351] The Polθ ATPase assay was used to evaluate the inhibitors of Polθ ATPase activity in vitro. The experiments were performed with a truncated Polθ protein (Polθ-Hel containing the helicase domain (67-894), ATP, and a single-stranded DNA oligo (5'CTGTCCTGCATGATG-3') in Polθ assay buffer (20 mM Tris-HCl (pH 8.8), 5 mM MgCl2, 0.01% Tween-20, 0.01% NP40, 0.01% BSA, 1 mM DTT). 2 pL of assay buffer, containing Polθ-Hel protein (0.5 nM) and DNA substrate (500 nM), were transferred to assay-ready plates containing 0.04 pL of compounds diluted in DMSO. After a 30-minute incubation at 23°C in the dark, the reaction was triggered by Petition 870250080361, dated 08 / 09 / 2025, pages 457 / 513 176 / 231 addition of 2 μL of ATP (60 μM) in assay buffer. After 60 minutes at 23°C, 4 μL of ADP-Glo™ reagent (Glo 1) were added, followed by 40 minutes of incubation, then 8 μL of ADP-Glo™ kinase detection reagent (Glo 2) were added followed by 60 minutes of incubation at 23°C. Luminescence was then measured with the Tecan F200 Infinite plate reader. Raw data were analyzed with GeneData to generate IC50 values.

[00352] The results are shown in Table 15 below. Table 15 - IC50 results of the Polθ ATPase assay Exemplo No Compound IC50 of Polθ ATPase 1 N-(6-chloro-1,3-benzothiazol-2-yl)-4-(2-chloro-5-methoxy-4pyridyl)-6-methyl-pyridine-3-carboxamida Nv___„Cl A7 O N-fY' Ch3 I. iç 3<^<^N^^S aj H ^C^ ^N^ *** 2 2'-chloro-N-(6-methanesulfonyl-1,3-benzothiazol-2-yl)-5'methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamida „ xx *** 3 2'-chloro-N-(6-cyano-1,3-benzothiazol-2-yl)-5'-methoxy-6methyl-[4,4'-bipyridine]-3-carboxamida ... Cf 1 Ã ir ...Xj : *** 4 2'-chloro-N-(6-iodo-1,3-benzothiazol-2-yl)-5'-methoxy-6methyl-[4,4'-bipyridine]-3-carboxamida mXâaP·' ..AJ *** Petition 870250080361, 08 / 09 / 2025, pág. 458 / 513 1ΊΊ / 231 5 N-(6-bromo-1,3-benzothiazol-2-yl)-2'-chloro-5'-methoxy-6methyl-[4,4'-bipyridine]-3-carboxamida -ΧΛ yy* ΛΓ! ' *** 6 2'-chloro-N-{5-chloro-[1,3]thiazol[5,4-d]pyrimidin-2-yl}-5'methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamida 1 χ í}= *** Ί 2'-chloro-N-{5-chloro-[1,3]thiazol[5,4-b]pyridin-2-yl}-5'methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamida sXÉ .- / ½ 1 χ í}= *** 8 3-(2-methoxyphenyl)-N-{[1,3]thiazol[5,4-d]pyrimidin-2yl}pyridine-4-carboxamida ... N-(6-bromo-1,3-benzothiazol-2-yl)-3-(2methoxyphenyl)pyridine-4-carboxamida ** 10 3-(2-methoxyphenyl)-N-{[1,3]thiazol[4,5-c]pyridin-2yl}pyridine-4-carboxamida 1 IX 2=7 * Petition 870250080361, 08 / 09 / 2025, pág. 459 / 513 178 / 231 11 3-(2-Methoxyphenyl)-N-{[1,3]thiazol[4,5-b]pyridin-2yl}pyridine-4-carboxamide -Ap. A} * 12 3-(2-methoxyphenyl)-N-[5-(trifluoromethyl)-1,3-benzothiazol2-yl]pyridine-4-carboxamide * 13 N-(5-chloro-1,3-benzothiazol-2-yl)-3-(2methoxyphenyl)pyridine-4-carboxamide ν' ' * 14 3-(2-methoxyphenyl)-N-{[1,3]thiazolo[5,4-b]pyridin-2yl}pyridine-4-carboxamide mJO aa 1 JL IA- * 15 N-(1,3-benzothiazol-2-yl)-3-(2-methoxyphenyl)pyridine-4carboxamide II rM j * * 16 N-(5-cyano-1,3-benzothiazol-2-yl)-3-(2methoxyphenyl)pyridine-4-carboxamide 'A. .-p .çr- ND Petition 870250080361, dated 08 / 09 / 2025, page 460 / 513 179 / 231 17 2'-chloro-5'-methoxy-6-methyl-N-[6-(morpholin-4-yl)-1,3benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide *** 18 2'-chloro-5'-methoxy-6-methyl-N-(6-nitro-1,3-benzothiazol-2-yl)-[4,4'-bipyridine]-3-carboxamide .. X^ / =\ ND 19 4-(2-chloro-5-methoxy-4-pyridyl)-N-[5-[(3R)-3hydroxypyrrolidin-1-yl]thiazol[5,4-d]pyrimidin-2-yl]-6-methylpyridine-3-carboxamide *** 20 2'-chloro-5'-methoxy-6-methyl-N-[5-(piperidin-1-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3carboxamide *** 21 2'-chloro-N-[5-(4,4-difluoropiperidin-1-yl)-[1,3]thiazolo[5,4d]pyrimidin-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3carboxamide ill Ab1 *** 22 2'-chloro-5'-methoxy-6-methyl-N-[5-(morpholin-4-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3carboxamide *** Petition 870250080361, de 08 / 09 / 2025, pág. 461 / 513 180 / 231 23 2 ' -chloro-N- {5 - [(3 S)-3-hidroxipyrrolidin-1 -yl] [l,3]thiazol[5,4-d]pyrimidin-2-yl}-5'-methoxi-6-methyl-[4,4'bipyridine] - 3 -carboxamida *** 24 2'-chloro-5'-methoxy-6-methyl-N-[5-(pyrrolidin-l-yl)[l,3]thiazol[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3carboxamida *** 25 2 ' -chloro-N- [5 -(3,3 -difluoropyrrolidin-1 -yl)[l,3]thiazol[5,4-d]pyrimidin-2-yl]-5'-methoxy-6-methyl-[4,4'- bipyridine] - 3 -carboxamida *** 26 2'-chloro-N-{5-[(3R)-3-hidroxipyrrolidin-l-yl][l,3]thiazol[5,4-d]pyrimidin-2-yl}-5'-methoxi-6-methyl-[4,4'- bipyridine] - 3 -carboxamida TJJ >= *** 27 2 ' -chloro-N- [5 -(1,1 -dioxo-1 Z6-thiomorpholin-4-yl)[l,3]thiazol[5,4-d]pyrimidin-2-yl]-5'-methoxy-6-methyl-[4,4'bipyridine] - 3 -carboxamida -AO* yyyyj- *** Petition 870250080361, 08 / 09 / 2025, pág. 462 / 513 181 / 231 28 2'-chloro-5'-methoxy-6-methyl-N-[5-(4-methylpiperazin-1-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide *** 29 2'-chloro-5'-methoxy-6-methyl-N-(5-{2-oxa-6azaspiro[3.3]heptan-6-yl}-[1,3]thiazolo[5,4-d]pyrimidin-2-yl)-[4,4'-bipyridine]-3-carboxamide *** 30 2'-chloro-5'-methoxy-N-{5-[(2-methoxyethyl)amino][1,3]thiazolo[5,4-d]pyrimidin-2-yl}-6-methyl-[4,4'bipyridine]-3-carboxamide *** 31 2'-chloro-N-[5-(3-hydroxyazetidin-1-yl)-[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide *** 32 2'-chloro-5'-methoxy-N-[5-(3-methoxypyrrolidin-1-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-6-methyl-[4,4'-bipyridine]-3-carboxamide *** Petition 870250080361, de 08 / 09 / 2025, pág. 463 / 513 182 / 231 33 2'-chloro-N-[5-(4-hydroxypiperidin-l-yl)-[l,3]thiazol[5,4d]pyrimidin-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3carboxamide *** 34 2'-chloro-5'-methoxy-6-methyl-N-{5-[(lS,4S)-2-oxa-5- azabicyclo[2.2.1]heptan-5-yl]-[l,3]thiazol[5,4-d]pyrimidin- 2-yl} - [4,4 ' -bipyridine] -3 -carboxamide T I *** 35 2'-chloro-N-[5-(3-cyanopiperidin-l-yl)-[l,3]thiazol[5,4d]pyrimidin-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3carboxamide ..AT* Λ *** 36A N-(6-amino-l,3-benzothiazol-2-yl)-4-(2-chloro-5-methoxy-4pyridyl)-6-methyl-pyridine-3-carboxamide jÇC .-o—. II 1 ** 36B 2'-chloro-5'-methoxy-6-methyl-N-[6-(2-oxopiperidin-l- yl)-l,3-benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide *** 37 4-(2-chloro-5-methoxy-4-pyridyl)-N-[5-(3,6-dihydro-2Hpyran-5-yl)thiazol[5,4-b]pyridin-2-yl]-6-methyl-pyridine-3carboxamide M -XL JL *** Petition 870250080361, de 08 / 09 / 2025, pág. 464 / 513 183 / 231 38 4-(2-chloro-5-methoxy-4-pyridyl)-N-[6-(5-chloro-2-pyridyl)1,3-benzothiazol-2-yl]-6-methyl-pyridine-3-carboxamide .XX .-ΧΛ—ΧΛ— i.7= χ χ N-[6-(5-chloropyridine-2-yl)-1,3-benzothiazol-2-yl]-3(2-methoxyphenyl)pyridine-4-carboxamide OO ---\ / ^\. Cl 1 II II \—f ch, JL IL / TIT N^ S 1 1 HN^ ** 40 2'-chloro-N-[6-(3-hydroxyoxolan-3-yl)-1,3-benzothiazol-2yl]-5'-methoxy-6-methyl-[4,4-3·-bicarboxyde-[4,4'-3·-bicarboxydene] k IÀ Xj s ** 41 2'-chloro-N-(6-methanosulfonamido-1,3-benzothiazol-2-yl)5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide ,ΧΪ. . Λ*. I. T 5 p )=7 Xj : ' *** 42 1 π x >= XJi ' 2'-chloro-5'-methoxy-6-methyl-N-{[1,3]thiazol[5,4- d]pyrimidine-2-yl}-[4,4' -bipyridine] - 1 ^*** 3-χ4carboxamide .,,χχ: 2′-chloro-5′-methoxy-6-methyl-N-[6-(methylsulfanyl)-1,3benzothiazol-2-yl]-[4,4′ -bipyridine]-3-carboxamide *** 44 1 χ χ 2= / Xj ' 1 2′-chloro-5′-methoxy-6-methyl-N-{[1,3]thiazol[5,4-c]peiidin- 2-yl}-[4,4′-bipyridine]-3-carboxamide *** Petition 870250080361, de 08 / 09 / 2025, pág. 465 / 513 184 / 231 45 N-[5-(4-acetylpiperazin-l-yl)-[l,3]thiazol[5,4-d]pyrimidin2-yl]-2'-chloro-5'-methoxy-6-metil-[4,4'-bipiridina]-3carboxamida *** 46 OH íí T λ—N / — 0nh h3ct X 2'-chloro-N-{5-[(2-hidroxietil)amino]-[1,3]thiazol[5,4d]pyrimidin-2-yl}-5'-methoxy-6-metil-[4,4'-bipyridina]-3carboxamida *** 47 nn · h3c or 2'-chloro-5'-methoxy-N-[5-(3-methoxyazetidin-l-yl)[l,3]thiazol[5,4-d]pyrimidin-2-yl]-6-metil-[4,4'-bipyridina]- 3-carboxamida *** 48 OH a-ÇC, ,vyP jYA h3ct X 2 ' -chloro-N- {5 - [(4-hydroxycyclo-hexyl)amino]- [l,3]thiazol[5,4-d]pyrimidin-2-yl}-5'-methoxy-6-methyl-[4,4'- bipyridine] - 3 -carboxamide *** 49 .1. -a· jyy^ Ui' ' í rac-2'-chloro-N-(5-{[(1R,3S)-3- hydroxycyclopentyl]amino}-[1,3]thiazolo[5,4-d]pyrimidin-2yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide *** 50 yy 2'-chloro-5'-methoxy-6-methyl-N-{5-[(3R)-3-methylmorpholin4-yl]-[1,3]thiazolo[5,4-d]pyrimidin-2yl}-[4,4'-bipyridine]-3carboxamide *** Petition 870250080361, dated 08 / 09 / 2025, p. 466 / 513 185 / 231 51 / 7 / HC Xa AH,cr 2'-chloro-5'-methoxy-6-methyl-N-{5-[(3S)-3-methylmorpholin4-yl]-[l,3]thiazol[5,4-d]pyrimidine-2-yl}-[4,4'-bipyridine=JO,JV)-c5-3carboxamide ) s 2'-chloro-5'-methoxy-6-methyl-N-{5-[(propan-2-yl)amino][l,3]thiazol[5,4-d]pyrimidine-2-yl}-[4,4'-bipyridine]-3carboxamide *** 53 HC^ ,JÍ JV? \ZY> 1 χ ΐ >=n \v jÔA s H3C TT 2'-chloro-5'-methoxy-6-methyl-N-(5-{2-oxa-7- azaspiro[3,5]nonan-7-yl}-[l,3]thiazol[4]'pyrimi [5,pyri-2-d, - 3 -carboxamide *** 54 ' ' JX JL ΑΓ / =· / ^ / 2'-chloro-N-(5-{3,8-diazabicyclo[3.2.l1octan-3-yl}ri,31thiazoir5,4-dlpyrimidine-2-yl-metho)[metho)-46,4'-me bipyridine1-3-carboxamide 55 2'-chloro-5'-methoxy-6-methyl-N-[5-(piperazin-l-yl)[l,3]thiazol[5,4-d]pyrimidine-2-yl]-[4,4'-bipyridine]-3carboxamide !j *** .. 2′-chloro-5′-methoxy-6-methyl-N-[6-(2-oxopyrrolidin-l-yl)l,3-benzothiazol-2-yl]-[4,4′-bipyridine]-3-carboxamide *** Petition 870250080361, dated 09 / 08 / 2025, pp. 467 / 513 186 / 231 57 .%xCi ο on^QO JP has HeC^^N^ 2'-chloro-5'-methoxy-6-methyl-N-[6-(3-oxomorpholin-4-yl)- 1,3-benzothiazole-2-yl]-[4,4'-bipyridine]-X-***-X5-carboxamide j^j S 2'-chloro-5'-methoxy-6-methyl-N-[6-(3-methyl-2oxoimidazolidin-1-yl)-1,3-benzothiazol-2-yl]-[4,4'bipyridine] - 3-carboxamide *** 59 Nx_.Cl O HSC. Xjl n AA^0 0^ 0 N\ J n^^s ÁJ h h3c n 2'-chloro-5'-methoxy-6-methyl-N-[6-(2-oxo-1,3-oxazolidin3-yl)-1,3-benzothiazol-2-yl]-[4,dynamide-N***3'-bi ο jrfyò hc^Nt 2'-chloro-5'-methoxy-6-methyl-N-[6-(2-oxoimidazolidin-1yl)-1,3-benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide *** 61 L< 2'-chloro-5'-methoxy-6-methyl-N-[6-(2-oxopiperidin-1-yl)[1,3]thiazol[4,5-c]pyridin-2-yl]-[4,4'-bipyridine]-3carboxamide *** 62 . N. Cl N H3C ky fí \ 3 0 N^\ / 1 X ϊ )=7 N^^^S 1 l| H ^C^^N^ 2'-chloro-5'-methoxy-6-methyl-N-{[1,3]thiazol[4,5-c]pyridine2-yl}-[4,4'-bipyridine]-3-carboxamide *** 63 2'-chloro-N-{6-chloro-[1,3]thiazol[5,4-c]pyridine-2-yl}-5'methoxy-6-methyl- [4,4' -bipyridine]-3-carboxamide *** Petition 870250080361, de 08 / 09 / 2025, pág. 468 / 513 187 / 231 64 -V- L. 1 JJ 5= / 2'-chloro-N-{6-chloro-[1,3]thiazol[4,5-c]pyridin-2-yl}-5'methoxy-6-methyl- [4,4' -bipyridine]-3-carboxamide *** 65 2'-chloro-5'-methoxy-6-methyl-N-[6-(morpholin-4-yl)[1,3]thiazol[4,5-c]pyridin-2-yl]-[4,4'-bipyridine]-3carboxamide *** 66 Jf —ZA xxx- 2'-chloro-N-[6-(dimethylsulfamoyl)-1,3-benzothiazol-2-yl]5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide *** 67 . - C'Y- / =\_ AL .aa^^ 2'-chloro-5'-methoxy-6-metil-N-[6-(morpholin-4-yl)[1,3]thiazol[4,5-b]pyridin-2-yl]-[4,4'-bipyridina]-3carboxamide *** 68 ALtCAy. 2'-chloro-N-[6-(4-hydroxypiperidin-1-yl)-[1,3]thiazol[4,5c]pyridin-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3carboxamide *** 69 NK H3C J / XC10—Assy HcANA nAA^ / N-(1,3-benzothiazol-2-yl)-2'-chloro-5'-methoxy-6-methyl[4,4'-bipyridine]-3-carboxamide *** 70 2'-chloro-5'-methoxy-6-methyl-N-[6-(2-oxopiperidin-1-yl)[1,3]thiazol[4,5-b]pyridin-2-yl]-[4,4'-bipyridine]-3carboxamide *** Petition 870250080361, de 08 / 09 / 2025, pág. 469 / 513 188 / 231 71 ,vTí JU1 ' 2'-chloro-N-[6-(4-hydroxypiperidin-1-yl)-[1,3]thiazol[4,5b]pyridin-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3carboxamide *** 72 -oo IJJ \=· \— / ..Λθ! ' 2'-chloro-5'-methoxy-6-methyl-N-[5-(morpholin-4-yl)[1,3]thiazol[5,4-b]pyridin-2-yl]-[4,4'-bipyridine]-3carboxamide *** 73 HAOpb IICV 2'-chloro-5'-methoxy-6-methyl-N-[5-(2-oxopiperidin-1-yl)[1,3]thiazol[5,4-b]pyridin-2-yl]-[4,4'-bipyridine]-3carboxamide *** 74 2'-chloro-N-[5-(4-hydroxypiperidin-1-yl)-[1,3]thiazol[5,4b]pyridin-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3carboxamide *** 75 A·^·- 2'-chloro-5'-methoxy-N-{5-methoxy-[1,3]thiazol[5,4-d]pyrimidin-2-yl}-6-methyl-[4,4'-bipyridine]-3-carboxamide *** 76 ..JU ' 2'-chloro-5'-methoxy-6-methyl-N-(5-{2-oxa-6- azaspiro[3.4]octan-6-yl}-[1,3]thiazol[5,4-d]pyrimidin-2-yl)[4,4'-bipyridine]-3-carboxamide *** Petition 870250080361, de 08 / 09 / 2025, pág. 470 / 513 189 / 231 77 2'-chloro-N-{5-[(2-hydroxy-2-methylpropyl)amino][1,3]thiazol[5,4-d]pyrimidin-2-yl}-5'-methoxy-6-methyl-[4,4'bipyridine] - 3-carboxamide *** 78 2'-chloro-5'-methoxy-6-methyl-N-{5-[(2-methylpropyl)amino][1,3]thiazol[5,4-d]pyrimidin-2-yl}-[4,4'-bipyridine]-3-carboxamide *** 79 2'-chloro-N-[5-(cyclobutylamino)-[1,3]thiazol[5,4d]pyrimidin-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide *** 80 2'-chloro-5'-methoxy-N-[5-(4-methoxypiperidin-1-yl)[1,3]thiazol[5,4-d]pyrimidin-2-yl]-6-methyl-[4,4'-bipyridine]3-carboxamide *** 81 2'-chloro-N-(5-{6-hydroxy-2-azaspiro[3.3]heptan-2-yl}[1,3]thiazol[5,4-d]pyrimidin-2-yl)-5'-methoxy-6-methyl-[4,4'bipyridine] - 3-carboxamide *** 82 XN S___Cl H3C / iT O^'XJ' H,C <XJÁ^X? 2’-cloro-5’-metoxi-6-metil-N-(5-{6-oxa-2- azaspiro[3.4]octan-2-il}-[1,3]tiazol[5,4-d]pirimidin-2-il)[4,4’-bipiridina]-3-carboxamida *** Petition 870250080361, de 08 / 09 / 2025, pág. 471 / 513 190 / 231 83 Ms X Γ ai 2 ' -chloro-N- {6- [imino(metil)oxo-Z6-sulfanyl] -1,3 benzothiazol-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3carboxamide *** 84 AC-pTS ,,xo 2' -chloro-N- [6-( 1,1 -dioxo-1 Z6,2-thiazolidin-2-yl)-1,3benzothiazol-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3carboxamide *** 85 2 ' -chloro-N- {6- [(4R)-4-hydroxy-2-oxopiperidin-1 -yl] -1,3 benzothiazol-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3carboxamide *** 86 Eypv wr 2'-chloro-5'-methoxy-6-methyl-N-[6-(4-methyl-2- oxopiperazin-1-yl)-1,3 -benzothiazol-2-yl]- [4,4 ' -bipyridine] 3-carboxamide *** 87 LA 2'-chloro-N-[5-(3,6-dihydro-2H-pyran-4-yl)-[l,3]thiazol[5,4d]pyrimidin-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3carboxamide *** 88 N-[5-(4-hydroxypiperidin-1-yl)-[l,3]thiazol[5,4d]pyrimidin-2-yl]-5 ' -methoxy-6-methyl-2 ' -(trifluoromethyl)[4,4'-bipyridine]-3-carboxamide *** Petition 870250080361, de 08 / 09 / 2025, pág. 472 / 513 191 / 231 89 N-[5-(4-hydroxypiperidin-1-yl)-[1,3]thiazol[5,4d]pyrimidin-2-yl]-5'-methoxy-6-metil-2'-(trifluorometil)[4,4'-bipiridina]-3-carboxamida *** 90 Mx·XX XXX·. 2'-chloro-5'-methoxy-6-methyl-N-[5-(trifluoromethyl)[1,3]thiazol[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3carboxamide *** 91 H3C Γ V-C1 o— •° 4 / CXh h3c^X .H.^S^^^ 2'-chloro-5'-methoxy-6-methyl-N-{5-methyl-[1,3]thiazol[5,4d]pyrimidin-2-yl}-[4,4' -bipyridine] - 3-carboxamide *** 92 5'-methoxy-2',6-dimethyl-N-[5-(morpholin-4-yl)[1,3]thiazol[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3carboxamide *** 93 H3C. Γ Vf O--\ _ / fy-i0 ?i HC^X HN—>=>KI / ^N 3 \^n \^0 2'-fluoro-5'-methoxy-6-methyl-N-[5-(morpholin-4-yl)[1,3]thiazol[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3carboxamide *** 94 2'-chloro-5'-methoxy-6-methyl-N-[5-(2-oxopiperidin-1-yl)[1,3]thiazol[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3carboxamide *** *** indicates an IC50 inferior to 100nM ** indicates an IC50 de 100nM to 1000nM * indicates an IC50 superior to 1000nM Petition 870250080361, dated 08 / 09 / 2025, pages 473 / 513 192 / 231 Examples - Part B Analytical

[00353] All solvents and chemical reagents were obtained from commercial sources and used without further purification or drying. NMR spectra were recorded on a Bruker Avance III HD 400 MHz, a Bruker NEO 400 MHz, a Bruker Avance III HD 500 MHz, a Bruker Avance NEO 500 MHz, or a Bruker Avance III HD 600 MHz spectrometer. Chemical shifts are quoted in ppm using non-deuterated solvent as the internal reference.

[00354] LCMS spectra were recorded on a Waters Aquity UPLC using method A: Waters UPLC® BEH™ C18 2.1 x 50 mm 1.7 µm column at 40°C, eluting with 0.1% formic acid in acetonitrile and 0.1% formic acid in water, using a gradient of 5-100% over 1.35 minutes at a rate of 0.9 mL / min; method B: Phenomenex Kinetix-XB C18 2.1 x 100 mm, 1.7 µm column at 40°C, eluting with 0.1% formic acid in acetonitrile and 0.1% formic acid in water, using a gradient of 5-100% over 5.8 minutes at a rate of 0.6 mL / min; method C: Waters UPLC® column Method A: Waters UPLC® BEH₂™ C18 2.1 x 50 mm 1.7 pm column at 55°C, eluting with 2 mM ammonium bicarbonate in water, buffered to pH 10, and acetonitrile using a gradient of 1-100% over 1.10 minutes at a rate of 1 mL / min; Method B: Waters UPLC® BEH₂™ C18 2.1 x 100 mm 1.7 pm column at 55°C, eluting with 2 mM ammonium bicarbonate in water, buffered to pH 10, and acetonitrile using a gradient of 5-100% over 5.30 minutes at a rate of 0.6 mL / min.Method E: Waters CSH C18 column, 2.1 x 50 mm, 1.7 µm at 55°C, eluting with 0.035% TFA in acetonitrile and 0.05% TFA in water, using a gradient from 2% to 98% over 1.5 minutes at a rate of 0.8 mL / min; Method F: Waters CSH C18 column, 2.1 x 50 mm, 1.7 µm at 55°C, eluting with 0.035% TFA in acetonitrile and 0.05% TFA in water, using a gradient from 2% to 98% over 1.5 minutes at a rate of 0.8 mL / min. Petition 870250080361, dated 09 / 08 / 2025, pp. 474 / 513 193 / 231 over 2.4 minutes at a rate of 0.8 mL / min, method G: Waters CSH C18 column 2.1 x 50 mm, 1.7 μm at 55 °C, eluting with 0.02% formic acid in acetonitrile and 0.02% formic acid in water, using a gradient from 2% to 98% over 4.5 minutes at a rate of 1 mL / min, or method H: Waters CSH C18 column 2.1 x 50 mm, 1.7 μm at 55 °C, eluting with 0.02% formic acid in acetonitrile and 0.02% formic acid in water, using a gradient from 2% to 98% over 2.4 minutes at a rate of 0.8 mL / min. Mass spectra were obtained using a Waters SQD, SQD2, or QDA detector with electrospray ionization in positive or negative mode. LCMS purity was determined by monitoring the AUC at 215, 220, 254, or 280 nm.

[00355] Preparative HPLC was performed using method A: Waters Sunfire C18 30 mm x 100 mm, 5 μm column at room temperature, using 30% formic acid 0.1% in acetonitrile and 70% formic acid 0.1% in water for 1.9 minutes, then a gradient of 30-95% formic acid 0.1% in acetonitrile for 9.6 minutes at a flow rate of 40 mL / min, method B: Waters XBridge C18 30 mm x 100 mm, 5 μm column at room temperature, using 30% acetonitrile and 70% ammonium hydroxide 0.2% in water for 2 minutes, then a gradient of 30-95% acetonitrile for 9.5 minutes at a flow rate of 40 mL / min, or method C: Waters Sunfire™ C18 column (30 mm x 100 mm, 5 gm; temperature: ambient temperature), with an injection volume of 1500 g / L at a flow rate of 40 mL / min with 10% B for 1.90 min, then a gradient of 10-95% B over 14.10 min and a holding time of 2.0 min, where A = 0.1% formic acid in water and B = 0.1% formic acid in acetonitrile.UV spectra were recorded at 215 nm using a Gilson detector. Experimental

[00356] The examples listed in Table 16 below were prepared in a manner analogous to the general procedure D described previously. Petition 870250080361, dated 08 / 09 / 2025, pages 475 / 513 194 / 231 Table 16 Exemplo Rendimento Pureza LCMS (%) LCMS Rt (min.) m / z Método de LCMS RMN 1H Exemplo 95 2’-cloro-N-(5-{[(2R)-2-hidroxipro pil]amino}-[1,3]tiazol[5,4-d]pirimi din-2- il)-5’-metoxi-6-metil-[4,4’-bipiridi na] - 3 -carboxamida 6,5 95 2,41 486,3 / 488,3 B RMN 1H (400 MHz, DMSO-d 6) δ 12,85 (s, 1H), 8,85 (s, 1H), 8,66 (s, 1H), 8,17 (s, 1H), 7,55 (s, 1H), 7,43 (s, 1H), 7,20 (s, 1H), 4,70 (d, J = 4,8 Hz, 1H), 3,86 3,75 (m, 1H), 3,63 (s, 3H), 3,28 3,22 (m, 2H), 2,60 (s, 3H), 1,08 (d, J = 6,2 Hz, 3H). Exemplo 96 2’-cloro-N-(5-{[(2S)-2-hidroxipro pil]amino}-[1,3]tiazol[5,4-d]pirimi din-2- il)-5’-metoxi-6-metil-[4,4’-bipiridi na] - 3 -carboxamida 8,8 95 2,43 486,3 / 488,3 B RMN 1H (400 MHz, DMSO-d 6) δ 8,84 (s, 1H), 8,62 (s, 1H), 8,15 (s, 1H), 7,56 - 7,36 (m, 2H), 4,68 (d, J = 4,8 Hz, 1H), 3,86 - 3,72 (m, 1H), 3,62 (s, 3H), 3,28 - 3,18 (m, 3H), 2,58 (s, 3H), 2,06 - 1,94 (m, 1H), 1,06 (d, J = 6,2 Hz, 3H).Example 97 2'-chloro-5'-methoxy-N-[5-(3-methoxy-3-methylazetidin-1-yl)-[1,3]thiazol[5,4-d]pyrimidin-2yl]-6-methyl-[4,4'-bipyridine]-3-carboxamide 41 100 2.92 512.3 / 514.3 B NMR - 3.86 (m, 2H), 3.62 (s, 3H), 3.21 (s, 3H), 2.60 (s, 3H), 1.47 (s, 3H). General Procedure H for the Preparation of 5-alkoxy-1,3-benzothiazol-2-amines

[00357] To a solution of 2-amino-1,3-benzothiazol-5-ol (1 equiv.) and potassium carbonate or cesium carbonate (2 equiv.) in acetone, DMF or acetonitrile (0.2 mmol / mL), the required alkyl halide (1.2 equiv.) was added and the reaction was stirred at 50°C until the reaction was considered complete by LCMS. The reaction mixture was diluted with water; if the product precipitated, it was filtered and dried in a vacuum oven. If the product Petition 870250080361, dated 08 / 09 / 2025, pages 476 / 513 If 195 / 231 did not precipitate, the aqueous mixture was extracted with ethyl acetate. The organic extracts were washed with brine solution, dried, and concentrated under reduced pressure. The residue was used in its crude state in the next stage or purified by automated chromatography with Biotage Isolera™ to provide the desired alkylated products. Intermediate I15 2-[(2-amino-1,3-benzothiazol-5-yl)oxy]acetonitrile

[00358] To a stirred suspension of 2-amino-1,3-benzothiazol-5-ol (202 mg, 1.2 mmol) and potassium carbonate (330 mg, 2.4 mmol) in acetone (6.0 mL), bromoacetonitrile (100 µL, 1.39 mmol) was added. The mixture was stirred at 50°C for 16 hours. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (2 ≈ 10 mL). The organic extracts were washed with brine and dried by filtration through hydrophobic filter paper. The crude residue was purified by automated chromatography with Biotage Isolera™ (25 g, Sfar Duo), eluting with a solvent gradient of 0-10% methanol in DCM to give the title compound (45 mg, 19%) as a beige powder. 1H NMR (400 MHz, DMSO-d6) δ 7.58 (d, J = 8.6 Hz, 1H), 7.53 (s, 2H), 7.06 (d, J = 2.6 Hz, 1H), 6.74 (dd, J = 8.6; 2.6 Hz, 1H), 5.16 (s, 2H). LCMS (method F) Rt 0.57 minute (100%), m / z 206.2 (M+H)+.

[00359] The intermediates in Table 17 below were prepared in a manner analogous to the general procedure H described above. Table 17 Intermediate Yield Purity LCMS (%) LCMS Rt (min.) m / z LCMS Method 1H NMR axaV Intermediate I16 2-[(2-amino-1,3-benzothiazol-5-yl)oxy]-N,N-dimethylacetamide 93 61 0.53 252.2 F Not registered Petition 870250080361, dated 08 / 09 / 2025, pages 477 / 513 196 / 231 -OT Intermediate I17 5-(propan-2-yloxy)-1,3-benzothiazol-2-amine 73 75 0.80 209.0 F Not registered r Intermediate I18 3-{[(2-amino-1,3-benzothiazol-5-yl)oxy]methyl}-1-λ-6-thietano-1,1-dione 2.6 70 0.58 285.2 F Not registered Intermediate I19 5-ethoxy-1,3-benzothiazol-2-amine unknown quantity 0.50 195.2 E Not registered Intermediate I20 5-[2-(trifluoromethoxy)ethoxy]-1,3-benzothiazol-2-amine 19 95 0.93 279.2 F 1H NMR (400 MHz, DMSO-d6) δ 7.51 (d, J = 8.6 Hz, 1H), 7.46 (s, 2H), 6.94 (d, J = 2.5 Hz, 1H), 6.66 (dd, J = 8.5; 2.5 Hz, 1H), 4.43 4.36 (m, 2H), 4.27 - 4.20 (m, 2H). Intermediate I21 1-(4-{[(2-amino-1,3-benzothiazol-5-yl)oxy]methyl}piperidin-1yl)ethan-1-one

[00360] To a stirred solution of N,Nisopropoxycarbonylaminocarbamate (338 µL, 1.71 mmol) in THF (9 mL), triphenylphosphine (1.07 g, 1.71 mmol) was added. The reaction mixture was cooled to 0°C, then 2-amino-1,3-benzothiazol-5-ol (250 mg, 1.43 mmol) and 1-[4-(hydroxymethyl)piperidin-1-yl]ethanone (260 mg, 1.57 mmol) were added. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was heated under reflux for 4 hours, then allowed to cool to room temperature overnight. The reaction mixture was filtered, and the filtrate was concentrated. Petition 870250080361, dated 08 / 09 / 2025, pages 478 / 513 197 / 231 under reduced pressure. The crude residue was purified by automated reverse-phase chromatography with Biotage Isolera™ (15 g, Cl8), using a solvent gradient of 0-100% acetonitrile in water with 0.1% acetic acid additive to give the title compound (335 mg, 65%) as a brown semisolid. LCM...

Claims

CLAIMS 1. A compound, or a pharmaceutically acceptable salt thereof, characterized in that it has the structural formula (I) shown below: (I) wherein: ring A is selected from the group consisting of phenyl and a 5- to 10-membered heteroaryl; R1 is selected from the group consisting of phenyl, 5- to 6-membered heteroaryl, 5- to 6-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl and 6- to 12-membered spiro-heterocyclyl, wherein: (i) R1 is optionally substituted with one or more R100 substituents; or two R100 substituents on adjacent atoms in the ring in R1 may be linked to form a fused cycloalkyl(3-6C) ring; or (ii) when it is a 5- to 6-membered heterocycline, a 6- to 10-membered bicyclic heterocycline, a 6- to 10-membered bridging heterocycline, and a 6- to 12-membered spiro-heterocycline, R1 is optionally replaced by oxo;wherein R100 is selected from the group consisting of halo, alkyl(1-4C), haloalkyl(1-4C), haloalkoxy(1-4C), cycloalkyl(3-6C), cycloalkyloxy(3-6C), -Q100-OH, -Q100-O-alkyl(1-4C), -C(O)-alkyl(1-4C) and -Q100-cyano; wherein Q100 is a (1-4C) alkylene or alkylene bond; the integers a and b are each independently 0 or 1; R2 and R3, when present, are each selected independently from the group consisting of halo, cyano, -O-, alkyl(1-4C), alkoxy(1-4C), haloalkyl(1-4C), hydroxyalkyl(1-4C), haloalkoxy(1-4C), -Q1-O-alkyl(1-4C), -C(O)OH, -Qi-C(O)-NH2, -Qi-C(O)NHMe and -Q1-C(O)-NMe2, where Qi is a (1-4C) alkylene or bond; X4 is selected from CRx4 or N; X5 is selected from CRx5 or N; X6 is selected from CRx6 or N; X7 is selected from CRx7 or N; Rx4 is hydrogen, fluorine, chlorine, methyl, or a group of the formula: -yq where: Y is -O-, -O-CH2-, -S-, -NH-, -CH2-, or -CH2-CH2-;Q is selected from hydrogen, alkyl(1-6C), -C(O)-NH2, -C(O)-NHMe, -C(O)-NMe2, cycloalkyl(3-8C), phenyl, heteroaryl, 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl and 6- to 12-membered spiro-heterocyclyl, wherein each of these is optionally substituted by one or more R100 substituents and a cycloalkyl(3-8C), 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl and 6- to 12-membered spiro-heterocyclyl is optionally substituted by oxo; Rx5 or Rx6 are selected from: hydrogen, halo, cyano, nitro, or a group of the formula: -L1-Y1-L2-Q1 wherein: L1 is absent or alkylene(1-2C);Y1 is absent or -O-, -S-, -SO-, -SO2-, -S(O)(=NRy1)-, -N(Ry1)-, Petition 870250080361, dated 08 / 09 / 2025, page 245 / 513 3 / 37 -C(O)-, -C(O)O-, -OC(O)-, -C(O)N(Ryi)-, -N(Ryi)C(O)-, -S(O)2N(Ryi)-, N(Ryi)SÜ2- or -N(Ryia)C(O)-N(Ryi)-, wherein Ryi and Ryia are selected from hydrogen or alkyl(i-2C); L2 is absent or alkylene(i-2C);and Qi is hydrogen, alkyl(i-6C), alkenyl(2-6C), alkynyl(26C), cycloalkyl(3-8C), phenyl, 5- to 6-membered heteroaryl, 4- to 7-membered heterocyclyl, 6- to i0-membered bicyclic heterocyclyl, 6- to i0-membered bridging heterocyclyl and 6- to i2-membered spiro-heterocyclyl, where: (i) when it is alkyl(i-6C), alkenyl(2-6C) or alkynyl(2-6C), Qi is optionally further substituted by one or more substituent groups independently selected from oxo, halo, cyano or by one or more groups of the formula: -Y2-Q2 wherein: Y2 is absent or selected from or -O-, -S-, -SO-, -SO2-, N(Ry2)-, -C(O)-, -C(O)O-, -OC(O)-, -C(O)N(Ry2)-, -N(Ry2)C(O)-, S(O)2N(Ry2)- or -N(Ry2)SO2-, wherein Ry2 is selected from hydrogen or alkyl(i-2C); Q2 is selected from: hydrogen; an alkyl(i-4C) that is optionally substituted by one or more substituents selected from halo, hydroxy, cyano, amino or alkoxy(i4C);or a 4- to 7-membered heterocyclic ring that is optionally substituted with one or more substituents selected from halo, hydroxy, cyano, amino, alkyl(i-4C) or alkoxy(i-4C); (ii) when it is cycloalkyl(3-8C), 4- to 7-membered heterocyclyl, 6- to i0-membered bicyclic heterocyclyl, bridge heterocyclyl of Petition 870250080361, dated 08 / 09 / 2025, page. 246 / 513 4 / 37 6 to 10 members and 6 to 12 members spiro-heterocyclyl, Qi is optionally further substituted by one or more substituent groups independently selected from oxo, halo, cyano or by one or more groups of the formula: -Y3-Q3 wherein: Y3 is absent or selected from or -O-, -S-, -SO-, -SO2-, N(Ry2)-, -C(O)-, -C(O)O-, -OC(O)-, -C(O)N(Ry3)-, -N(Ry3)C(O)-, S(O)2N(Ry3)- or -N(Ry3)SO2-, wherein Ry3 is selected from hydrogen or (1-2C) alkyl; Q3 is selected from: hydrogen;an alkyl(1-4C) group that is optionally substituted with one or more substituents selected from halo, hydroxy, cyano, amino, or alkoxy(1-4C); or a 4- to 7-membered heterocyclic ring that is optionally substituted with one or more substituents selected from halo, hydroxy, cyano, amino, alkyl(1-4C), or alkoxy(1-4C); (iii) when it is a 5- to 6-membered phenyl or heteroaryl group, Qi is optionally further substituted with one or more substituent groups independently selected from halo, cyano, or from one or more groups of the -Y3-Q3 formula defined above; Rx7 is selected from hydrogen, fluorine, chlorine, hydroxy, NH2, methyl, or CF3; or Rx4 and Rx5, Rx5 and Rx6 or Rx6 and Rx7 are linked in such a way that, together with the carbon atoms to which they are attached, they form a fused cycloalkyl(5-6C), phenyl, 5- or 6-membered heteroaryl or 5- or 6-membered heterocyclic ring, wherein each of these is optionally substituted with fluorine, chlorine, methyl or hydroxyl;Petition 870250080361, dated 08 / 09 / 2025, page 247 / 513 5 / 37 on the condition that: (i) when X5 is CRx5 and Rx5 is a group of the formula -L1-Y1L2-Q1, X6 is then selected from N, CH, CF, C-CN, C-Cl or C-Me; and (ii) when X6 is CRx6 and Rx6 is a group of the formula -L1-Y1L2-Q1, X5 is then selected from N, CH, CF, C-Cn, C-Cl or C-Me.; 2. Compound according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that: (i) when X5 is CRx5 and Rx5 is cyan or a group of the formula -L1-Y1-L2-Q1, then: X4 is selected from N, CH, CF, C-Cl or C-Me; X6 is selected from N, CH, CF, C-CN, C-Cl or C-Me; X7 is selected from N, CH, CF, C-Cl or C-Me; and (ii) when X6 is CRx6 and Rx6 is cyan or a group of the formula -L1-Y1-L2-Q1, then: X4 is selected from N, CH, CF, C-Cl or C-Me; X5 is selected from N, CH, CF, C-Cl or C-Me; X7 is selected from N, CH, CF, C-Cl or C-Me.

3. A compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized in that ring A is selected from 5, 6, 9 or 10 membered phenyl or heteroaryl groups.

4. A compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, characterized in that ring A is selected from: (i) phenyl, pyridinyl, pyridazinyl, pyrimidinyl, imidazolyl, pyrazolyl, triazolyl, imidazo[1,2-a]pyridinyl, [1,2,3]triazol[1,5-a]pyridinyl, imidazo[1,5-a]pyridinyl, pyrrol[2,3-b]pyridinyl, pyrrol[3,2-b]pyridinyl, pyrazol[1,5-a]pyridinyl, [1,2,4]triazol[1,5-a]pyridinyl, 1,6-naphthyridinyl, or 1,7-naphthyridinyl; (ii) phenyl, pyridinyl, pyrimidinyl, imidazo[l,2-a]pyridinyl, Petition 870250080361, of 09 / 08 / 2025, p. 248 / 513 6 / 37 1,2,3-triazole, pyrazolyl, isoxazolyl, imidazo[1,5-a]pyridinyl; (iii) phenyl, pyridinyl, pyrimidinyl and imidazo[1,2-a]pyridinyl; (iv) phenyl or pyridyl; (v) pyridyl.

5. A compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, characterized in that ring A is selected from: ; ; where indicates the point of attachment to the amide group of formula I; and R1, R2, R3, and R4 are as defined in claim 1.

6. A compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, characterized in that ring A is selected from: ; or where indicates the point of attachment to the amide group of formula I; and R1, R2, R3, a and b are as defined in this patent application.

7. Compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, characterized in that ring A is selected from: ; or where indicates the point of attachment to the amide group of formula I; and R1, R2, R3, and R4 are as defined in claim 1.

8. Compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, characterized in that ring A is selected from: (i) Bl1· ; Bl1· ; or ; or (ii) ; or where indicates the point of attachment to the amide group of formula I; and R1, R2, R3, a and b are as defined in claim 1.

9. A compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, characterized in that R1 is selected from one of the following options: (i) a 5- to 6-membered phenyl or heteroaryl group, each of which is optionally substituted with one or more R100 substituents as defined in claim 1; or two R100 substituents on adjacent atoms in the ring in R1 may be linked to form a fused cycloalkyl(3-6C) ring; or (ii) a 6-membered phenyl or heteroaryl group, each of which is optionally substituted with one or more R100 substituents as defined in claim 1; or two R100 substituents on adjacent atoms in the ring in R1 may be linked to form a fused cycloalkyl(3-6C) ring.

10. A compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, characterized in that R1 is selected from one of the following options: (i) a group of the formula OVW or 'Λ~ν wherein: indicates the point of attachment to ring A of formula I; X8 is CH or N; R100a, R100b and Riooc are R100 substituent groups as defined in claim 1; and the integers c, d and e are 0, 1 or 2; (ii) a group of the formula: wherein: indicates the point of attachment to ring A of formula I; X8 is CH or N; R100a and R100b are both R100 substituent groups as defined in claim 1; and the integers c and d are 0, 1 or 2; (iii) a group of the formula: Petition 870250080361, dated 09 / 08 / 2025, p.251 / 513 9 / 37 where: indicates the point of attachment to ring A of formula I; X8 is CH or N; R100a, R100b and Riooc are R100 substituent groups as defined in claim 1; and the integers d and e are 0 or 1; (iv) a group of the formula: or where: indicates the point of attachment to ring A of formula I; X8 is CH or N; R100a and R100b are both R100 substituent groups as defined in claim 1; and the integer d is 0 or 1; (v) a group of the formula: . / wv , jvw or where: indicates the point of attachment to ring A of formula I; R100b is methyl, fluorine or chlorine; Riooc is fluorine or chlorine, especially fluorine; (vi) a group of the formula: Petition 870250080361, of 09 / 08 / 2025, p. 252 / 513 10 / 37 where: indicates the point of attachment to ring A of formula I; Rioob is fluorine or chlorine; or (vii) a group of the formula: where: indicates the point of attachment to ring A of formula I.

11. A compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, characterized in that R100 is selected from one of the following options: (i) halo, alkyl(1-3C), haloalkyl(1-3C), haloalkoxy(1-3C), cycloalkyl(3-6C), cycloalkyloxy(3-6C), -Q100-OH, -Q100-O-alkyl(1-3C), C(O)-alkyl(1-3C) and -Q100-cyano; where Q100 is a (13C)alkylene linkage; (ii) halo, alkyl(1-2C), haloalkyl(1-2C), haloalkoxy(1-2C), cycloalkyl(3-6C), cycloalkyloxy(3-6C), -Q100-OH, -Q100-O-alkyl(1-2C), C(O)-alkyl(1-2C) and -Q100-cyano; where Q100 is a linkage or alkylene(1-2C); (iii) halo, alkyl(1-2C), fluoroalkyl(1-2C), fluoroalkoxy(12C), cycloalkyl(3-6C), cycloalkyloxy(3-6C), -Q100-OH, -Q100-O-alkyl(12C), -C(O)-alkyl(1-2C) and -Q100-cyano; where Q100 is a linkage or alkylene(1-2C); (iv) halo, alkyl(1-2C), fluoroalkyl(1-2C), -Q-OH, -Q100-Oalkyl(1-2C), -C(O)-alkyl(1-2C) and -Q100-cyano;where Q100 is a linkage or alkylene(1-2C); (v) halo, alkyl(1-2C), fluoroalkyl(1-2C), -Q-OH and -Q-O-alkyl(1-2C); where Q is a linkage or alkylene(1-2C); (vi) fluorine, chlorine, alkyl(1-2C), fluoroalkyl(1-2C), -Q100-OH and -Q100-O-alkyl(1-2C); where Q100 is a linkage or alkylene(1-2C); or (vii) fluorine, chlorine, methyl, fluoromethyl(1-2C) and -Q100-O-alkyl(1-2C); where Q100 is a linkage or methylene.; 12. A compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, characterized in that: (i) the integer a is 0 or 1 and the integer b is 0; (ii) the integer a is 0 and the integer b is 0; (iii) the integer a is 1 and the integer b is 0.

13. A compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, characterized in that R2 and R3, when present, are each independently selected from: (i) the group consisting of fluorine, chlorine, alkyl(1-2C), alkoxy(1-2C), haloalkyl(1-2C), hydroxyalkyl(1-2C), haloalkoxy(1-2C), -Q1-Oalkyl(1-2C) and -C(O)OH, where Q1 is a linkage or alkylene(1-2C); (ii) the group consisting of fluorine, chlorine, alkyl(1-2C), alkoxy(1-2C) or haloalkyl(1-2C); (iii) the group consisting of fluorine, alkyl(1-2C) or alkoxy(1-2C); or (iv) methyl.

14. Compound, or a pharmaceutically acceptable salt thereof, characterized in that it has one of the following formulas Ia to Iac shown below: Petition 870250080361, dated 08 / 09 / 2025, p. 254 / 513 12 / 37 Ia Ib Ic Ie li lj Petition 870250080361, dated 09 / 08 / 2025, p. 255 / 513 13 / 37 Mil· Mil· Im Ip iq It Petition 870250080361, dated 09 / 08 / 2025, p. 256 / 513 14 / 37 ill lac lad lae Petition 870250080361, dated 09 / 08 / 2025, p. 257 / 513 15 / 37 lag lak where: lam the ring A, R1, the integer a, the integer b, R2, R3, X4, X5, X6, X7, Rx5 and Rx6 are as defined in any of claims 1 to 13 or 15 to 21; X8 is CH or N; R100a, R100b and R100c are both R100 as defined in claim 1; and the integers c, d and e are 0 or 1. Petition 870250080361, dated 09 / 08 / 2025, p. 258 / 513 16 / 37 15. A compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, characterized in that X4, X5, X6 and X7 are selected from one of the following options: (i) X4 is selected from CRx4 or N; X5 is selected from CRx5 or N; X6 is selected from CRx6; X7 is selected from CRx7 or N; (ii) X4 is selected from CRx4; X5 is selected from CRx5 or N; X6 is selected from CRx6; X7 is selected from CRx7 or N; (iii) X4 is selected from CRx4; X5 is selected from CRx5 or N; X6 is selected from CRx6; X7 is selected from CH or N; (iv) X4 is selected from CH; X5 is selected from CRx5 or N; X6 is selected from CRx6; X7 is selected from CH or N; (v) X4 is selected from CH; X5 is selected from CH or N; X6 is selected from CRx6; X7 is selected from CH or N; (vi) X4 is selected from CH; X5 is selected from CH; X6 is selected from CRx6;X7 is selected from CH or N; (vii) X4 is selected from CH; Petition 870250080361, dated 08 / 09 / 2025, page 259 / 513 17 / 37 X5 is selected from CH or N; Xô is selected from CRx6; X7 is selected from CH; (viii) X4 is selected from CH; X5 is selected from CH; X6 is selected from CRx6; X7 is selected from CH; (ix) X4 is selected from CH; X5 is selected from N; X6 is selected from CRx6; X7 is selected from CH; (x) X4 is selected from CH; X5 is selected from CH; X6 is selected from CRx6; X7 is selected from N; (xi) X4 is selected from CH; X5 is selected from N; X6 is selected from CRx6; X7 is selected from N; (xii) X4 is selected from CH or N; X5 is selected from CRx5; X6 is selected from CH or N; X7 is selected from CH or N; (xiii) X4 is selected from CH; X5 is selected from CRx5; X6 is selected from CH; X7 is selected from CH; (xvi) X4 is selected from CH;X5 is selected from CRx5; Petition 870250080361, dated 08 / 09 / 2025, page 260 / 513 18 / 37 Xô is selected from N; X7 is selected from CH; (xv) X4 is selected from CH; X5 is selected from CRx5; Xô is selected from CH; X7 is selected from N; (xvi) X4 is selected from N; X5 is selected from CRx5; Xô is selected from CH; X7 is selected from CH; (xvii) X4 is selected from N; X5 is selected from CRx5; Xô is selected from N; X7 is selected from CH. 1ô. Compound according to claim 14, or a pharmaceutically acceptable salt thereof, characterized in that X4, X5, Xô and X7 are selected from one of the following options: (i) X4 is selected from CH; X5 is selected from CH or N; Xô is selected from CRxô; X7 is selected from CH or N; (ii) X4 is selected from CH; X5 is selected from CH; Xô is selected from CRxô; X7 is selected from CH or N; (iii) X4 is selected from CH;X5 is selected from CH or N; Xô is selected from CRxô; X7 is selected from CH; Petition 870250080361, dated 08 / 09 / 2025, page 261 / 513 19 / 37 (iv) X4 is selected from CH; X5 is selected from CH; X6 is selected from CRx6; X7 is selected from CH; (v) X4 is selected from CH; X5 is selected from N; X6 is selected from CRx6; X7 is selected from CH; (vi) X4 is selected from CH; X5 is selected from CH; X6 is selected from CRx6; X7 is selected from N; (vii) X4 is selected from CH; X5 is selected from N; X6 is selected from CRx6; X7 is selected from N; (viii) X4 is selected from CH; X5 is selected from CRx5; X6 is selected from CH; X7 is selected from CH.; 17. Compound according to claim 14, or a pharmaceutically acceptable salt thereof, characterized in that X4, X5, X6 and X7 are selected from one of the following options: (i) X4 is selected from CH; X5 is selected from CH; X6 is selected from CRx6; X7 is selected from CH; (ii) X4 is selected from CH; X5 is selected from N; Petition 870250080361, dated 08 / 09 / 2025, page 262 / 513 20 / 37 Xô is selected from CRxô; X7 is selected from CH; (iii) X4 is selected from CH; X5 is selected from CH; Xô is selected from CRxô; X7 is selected from N; (iv) X4 is selected from CH; X5 is selected from N; Xô is selected from CRxô; X7 is selected from N; (v) X4 is selected from CH; X5 is selected from CRx5; Xô is selected from CH; X7 is selected from CH.

18. Compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, characterized in that Rx4 is selected from one of the following options: (i) hydrogen, fluorine, chlorine, methyl or a group of the formula: -YQ wherein: Y is -O-, -S-, -NH- or -CH2-; Q is selected from hydrogen, alkyl(1-4C), cycloalkyl(3-0C), phenyl, 5- or 0-membered heteroaryl, 4- to 7-membered heterocyclyl, each of which is optionally substituted by one or more substituents R100 and a cycloalkyl(3-8C) and 4- to 7-membered heterocyclyl is optionally substituted by oxo; (ii) hydrogen, fluorine, methyl or a group of the formula: -YQ wherein: Petition 870250080361, dated 08 / 09 / 2025, p. 263 / 513 21 / 37 Y is -O-, -S-, -NH- or -CH2-; Q is selected from hydrogen, alkyl(1-4C), cycloalkyl(3-6C), phenyl, 5- or 6-membered heteroaryl, 4- to 7-membered heterocyclyl; (iii) hydrogen, fluorine, chlorine or methyl; or (iv) hydrogen.

19. A compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, characterized in that Rx5 or Rx6 are selected from hydrogen, halo, cyano, nitro or a group of the formula: -L1-Y1-L2-Q1 wherein: L1 is absent or alkylene(1-2C); Y1 is absent or -O-, -S-, -SO-, -SO2-, -S(O)(=NRy1)-, -N(Ry1)-, -C(O)-, -C(O)O-, -OC(O)-, -C(O)N(Ry1)-, -N(Ry1)C(O)-, -S(O)2N(Ry1)-, N(Ry1)SO2- or -N(Ry1a)C(O)-N(Ry1)-, wherein Ry1 and Ry1a are selected from hydrogen or alkyl(1-2C); L2 is absent or alkylene(1-2C);and Q1 is hydrogen, alkyl(1-6C), cycloalkyl(3-8C), phenyl, 5- to 6-membered heteroaryl, 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl and 6- to 12-membered spiro-heterocyclyl, wherein: (i) when it is alkyl(1-4C), Q1 is optionally further substituted by one or more substituent groups independently selected from oxo, halo, cyano or by one or more groups of the formula: -Y2-Q2 wherein: Petition 870250080361, dated 08 / 09 / 2025, page. 264 / 513 22 / 37 Y2 is absent or selected from or -O-, -SO2-, -N(Ry2)-, C(O)-, -C(O)N(Ry2)-, -N(Ry2)C(O)-, -S(O)2N(Ry2)- or -N(Ry2)SO2-, wherein Ry2 is selected from hydrogen or methyl; Q2 is selected from: hydrogen; an alkyl(1-4C) that is optionally substituted by one or more substituents selected from halo, hydroxy, cyano, amino or alkoxy(14C);or a 4- to 7-membered heterocyclic ring that is optionally substituted with one or more substituents selected from halo, hydroxy, cyano, amino, alkyl(1-4C) or alkoxy(1-4C); (ii) when Q1 is a cycloalkyl(3-8C), 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl and 6- to 12-membered spiro-heterocyclyl, it is optionally further substituted by one or more substituent groups independently selected from oxo, halo, cyano or by one or more groups of the formula: -Y3-Q3 wherein: Y3 is absent or selected from or -O-, -SO2-, -N(Ry3)-, C(O)-, -C(O)N(Ry3)-, -N(Ry3)C(O)-, -S(O)2N(Ry3)- or -N(Ry3)SO2-, wherein Ry3 is selected from hydrogen or methyl; Q3 is selected from: hydrogen; an alkyl(1-4C) group that is optionally substituted with one or more substituents selected from halo, hydroxy, cyano, amino or alkoxy(14C);or a 4- to 7-membered heterocyclic ring that is optionally substituted with one or more substituents selected from halo, hydroxy, cyano, amino, alkyl(1-4C) or alkoxy(1-4C); (iii) when it is a 5- to 6-membered phenyl or heteroaryl ring, Qi is optionally further substituted with one or more substituent groups selected independently from halo, cyano or one or more groups of the -Y3-Q3 formula defined above.

20. A compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, characterized in that Rx5 or Rx6 are selected from hydrogen, halo, cyano, nitro or a group of the formula: -L1-Y1-L2-Q1 wherein: L1 is absent or methylene; Y1 is absent or -O-, -SO2-, -S(O)(=NRy1)-, -N(Ry1)-, C(O)N(Ry1)-, -N(Ry1)C(O)-, -S(O)2N(Ry1)- or -N(Ry1)SO2-, wherein Ry1 and Ry1a are selected from hydrogen or (1-2C) alkyl; L2 is absent or methylene;and Q1 is hydrogen, (1-4C) alkyl, (3-4C) cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl and 6- to 12-membered spiroheterocyclyl, wherein: (i) when it is (1-4C) alkyl, Q1 is optionally further substituted by one or more substituent groups independently selected from halo, cyano or by one or more groups of the formula: -Y2-Q2 wherein: Y2 is absent or selected from or -O-, -SO2-, -N(Ry2)-, C(O)-, -C(O)N(Ry2)- or -N(Ry2)C(O)-, -S(O)2N(Ry2)- or -N(Ry2)SO2-, wherein Ry2 is selected from hydrogen or methyl; Petition 870250080361, dated 08 / 09 / 2025, page 266 / 513 24 / 37 Q2 ​​is selected from: hydrogen; an alkyl(1-4C) optionally substituted by one or more halos; or a 4- to 7-membered heterocyclic ring;(ii) when it is a cycloalkyl(3-6C), 4- to 7-membered heterocyclyl, 6- to 10-membered bicyclic heterocyclyl, 6- to 10-membered bridging heterocyclyl and 6- to 12-membered spiro-heterocyclyl, Qi is optionally further substituted by one or more substituent groups independently selected from oxo, halo, cyano or by one or more groups of the formula: -Y3-Q3 wherein: Y3 is absent or selected from or -O-, -SO2-, -N(Ry3)-, C(O)-, -C(O)N(Ry3)-, -N(Ry3)C(O)-, -S(O)2N(Ry3)- or -N(Ry3)SO2-, wherein Ry3 is selected from hydrogen or methyl; Q3 is selected from: hydrogen; an alkyl(1-4C) optionally substituted by one or more halo; or a 4- to 7-membered heterocyclic ring; (iii) when it is a 5- to 6-membered phenyl or heteroaryl group, Qi is optionally further substituted by one or more substituent groups selected independently from halo, cyano, or by one or more groups of the -Y3-Q3 formula defined above.

21. Compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, characterized in that Rx7 is selected from one of the following options: (i) hydrogen, fluorine, chlorine or methyl; or Petition 870250080361, dated 09 / 08 / 2025, p. 267 / 513 25 / 37 (ii) hydrogen.

22. A compound according to any one of claims 14 to 21, or a pharmaceutically acceptable salt thereof, characterized in that: (i) X8 is N; R100a and R100b are both R100 as defined in claim 1 or 11; and the integers ced are 0 or 1; (ii) X8 is CH; R100a and R100b are both R100 as defined in claim 1 or 11; and the integers ced are 0 or 1; (iii) X8 is N; R100a and R100b are both R100 as defined in claim 11; and the integers ced are 0 or 1; (iv) X8 is CH; R100a and R100b are both R100 as defined in claim 11; and the integers ced are 0 or 1.

23. Compound according to any one of claims 1 to 22, or a pharmaceutically acceptable salt thereof, characterized in that X4, X5, X6 and X7 are selected from the following options: (i) X4 is selected from CH; X5 is selected from N; X6 is selected from CRx6; and X7 is selected from N; or (ii) X4 is selected from CH; X5 is selected from N; Petition 870250080361, dated 08 / 09 / 2025, page 268 / 513 26 / 37 Xô is selected from CRx6; and X7 is selected from CH.

24. Compound according to claim 23, or a pharmaceutically acceptable salt thereof, characterized in that Ri is selected from a group of the formula: wherein indicates the point of attachment to ring A of formula I.

25. Compound according to claim 23 or 24, or a pharmaceutically acceptable salt thereof, characterized in that ring A is selected from: Ri La Ta jT J í Ύ r2 N ; or xX ; wherein indicates the point of attachment to the amide group of formula I; and Ri and R2 are as defined in claim i.

26. Compound, characterized by being selected from any of the following, or a pharmaceutically acceptable salt thereof: N-(6-chloro-1,3-benzothiazol-2-yl)-4-(2-chloro-5-methoxy-4-pyridyl)-6-methyl-pyridine-3-carboxamide; 2'-chloro-N-(6-methanesulfonyl-1,3-benzothiazol-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-(6-cyano-1,3-benzothiazol-2-yl)-5'-methoxy-6-methyl[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-(6-iodo-1,3-benzothiazol-2-yl)-5'-methoxy-6-methyl[4,4'-bipyridine]-3-carboxamide; Petition 870250080361, of 09 / 08 / 2025, p. 269 / 513 27 / 37 N-(6-bromo-1,3-benzothiazol-2-yl)-2'-chloro-5'-methoxy-6-methyl[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-{5-chloro-[1,3]thiazol[5,4-d]pyrimidin-2-yl}-5'methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-{5-chloro-[1,3]thiazol[5,4-b]pyridin-2-yl}-5'-methoxy6-methyl-[4,4'-bipyridine]-3-carboxamide; 3-(2-methoxyphenyl)-N-{[1,3]thiazol[5,4-d]pyrimidin-2-yl}pyridine4-carboxamide;N-(6-bromo-1,3-benzothiazol-2-yl)-3-(2-methoxyphenyl)pyridine-4-carboxamide; 3-(2-methoxyphenyl)-N-{[1,3]thiazol[4,5-c]pyridin-2-yl}pyridine-4-carboxamide; 3-(2-methoxyphenyl)-N-{[1,3]thiazol[4,5-b]pyridin-2-yl}pyridine-4-carboxamide; 3-(2-methoxyphenyl)-N-[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]pyridine-4-carboxamide; N-(5-chloro-1,3-benzothiazol-2-yl)-3-(2-methoxyphenyl)pyridine-4-carboxamide; 3-(2-methoxyphenyl)-N-{[1,3]thiazol[5,4-b]pyridin-2-yl}pyridine-4-carboxamide; N-(1,3-benzothiazol-2-yl)-3-(2-methoxyphenyl)pyridine-4-carboxamide; N-(5-cyano-1,3-benzothiazol-2-yl)-3-(2-methoxyphenyl)pyridine-4-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(morpholin-4-yl)-1,3benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-(6-nitro-1,3-benzothiazol-2-yl)[4,4'-bipyridine]-3-carboxamide; 4-(2-chloro-5-methoxy-4-pyridyl)-N-[5-[(3R)-3-hydroxypyrrolidine Petition 870250080361, of 08 / 09 / 2025, p. 270 / 513 28 / 37 1-yl]thiazol[5,4-d]pyrimidin-2-yl]-6-methyl-pyridine-3-carboxamide;2'-chloro-5'-methoxy-6-methyl-N-[5-(piperidin-1-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-[5-(4,4-difluoropiperidin-1-yl)-[1,3]thiazolo[5,4d]pyrimidin-2-yl]-5'-methoxy-6-methyl- [4,4'-bipyridine]-3 -carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(morpholin-4-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-{5-[(3S)-3-hydroxypyrrolidin-1-yl]-[1,3]thiazolo[5,4d]pyrimidin-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(pyrrolidin-1-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-[5-(3,3-difluoropyrrolidin-1-yl)-[1,3]thiazolo[5,4d]pyrimidin-2-yl]-5'-methoxy-6-methyl- [4,4'-bipyridine]-3 -carboxamide; 2'-chloro-N-{5-[(3R)-3-hydroxypyrrolidin-1-yl]-[1,3]thiazolo[5,4d]pyrimidin-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-[5-(1,1-dioxo-1Z6-thiomorpholin-4-yl)-[1,3]thiazolo[5,4d]pyrimidin-2-yl]-5'-methoxy-6-methyl- [4,4'-bipyridine]-3 -carboxamide;2'-chloro-5'-methoxy-6-methyl-N-[5-(4-methylpiperazin-1-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-(5-{2-oxa-6azaspiro[3.3]heptan-6-yl}-[1,3]thiazolo[5,4-d]pyrimidin-2-yl)-[4,4'-bipyridine]-3carboxamide; 2'-chloro-5'-methoxy-N-{5-[ (2-methoxyethyl)amino]-[1,3]thiazolo[5,4d]pyrimidin-2-yl}-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N -[5-(3-hydroxyazetidin-1-yl)-[1,3]thiazol[5,4d]pyrimidin-2-yl]-5'-methoxy-6-methyl- [4,4'-bipyridine]-3 -carboxamide; 2'-chloro-5'-methoxy-N-[5-(3-methoxypyrrolidin-1-yl)[1,3]thiazol[5,4-d]pyrimidin-2-yl]-6-methyl-[4,4'-bipyridine] -3-carboxamide; 2'-chloro-N-[5-(4-hydroxypiperidin-1-yl)-[1,3]thiazol[5,4 Petition 870250080361, of 08 / 09 / 2025, p. 271 / 513 29 / 37 d]pyrimidin-2-yl]-5'-methoxy-6-methyl- [4,4'-bipyridine]-3 -carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-{5-[(1S,4S)-2-oxa-5azabicyclo[2.2.1]heptan-5-yl]-[1,3]thiazol[5,4-d]pyrimidin-2-yl}-[4,4'bipyridine]-3-carboxamide;2'-chloro-N-[5-(3-cyanopiperidin-1-yl)-[1,3]thiazolo[5,4d]pyrimidin-2-yl]-5'-methoxy-6-methyl- [4,4'-bipyridine]-3-carboxamide; N-(6-amino-1,3-benzothiazol-2-yl)-4-(2-chloro-5-methoxy-4pyridyl)-6-methyl-pyridine-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(2-oxopiperidin-1-yl)-1,3-benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide; 4-(2-chloro-5-methoxy-4-pyridyl)-N-[5-(3,6-dihydro-2H-pyran-5yl)thiazolo[5,4-b]pyridin-2-yl]-6-methyl-pyridine-3-carboxamide; 4-(2-chloro-5-methoxy-4-pyridyl)-N-[6-(5-chloro-2-pyridyl)-1,3benzothiazol-2-yl]-6-methyl-pyridine-3-carboxamide; N-[6-(5-chloropyridin-2-yl)-1,3-benzothiazol-2yl]-3-(2-methoxyphenyl)pyridine-4-carboxamide; 2' -chloro-N - [6-(3 -hydroxyoxolan-3-yl)-1,3 -benzothiazol-2yl] - 5' -methoxy-6-methyl- [4,4' -bipyridine] -3 -carboxamide; 2'-chloro-N-(6-methanesulfonamido-1,3-benzothiazol-2yl)-5 ' -methoxy-6-methyl- [4,4' -bipyridine] -3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-{[1,3]thiazol[5,4-d]pyrimidin-2yl}-[4,4'-bipyridine] -3-carboxamide;2'-chloro-5'-methoxy-6-methyl-N-[6-(methylsulfanyl)-1,3benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-{[1,3]thiazol[5,4-c]pyridin-2-yl}[4,4'-bipyridine]-3-carboxamide; N-[5-(4-acetylpiperazin-1-yl)-[1,3]thiazol[5,4-d]pyrimidin-2-yl]2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine] -3-carboxamide; 2'-chloro-N -{5-[(2-hydroxyethyl)amino] -[1,3 ]thiazol[5,4 Petition 870250080361, of 08 / 09 / 2025, pág. 272 / 513 30 / 37 d]pyrimidin-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-N-[5-(3-methoxyazetidin- 1-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-6-methyl-[4,4'-bipyridine] -3-carboxamide; 2'-chloro-N-{5-[(4-hydroxycyclohexyl)amino]-[1,3]thiazolo[5,4d]pyrimidin-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; rac-2'-chloro-N-(5-{[(1R,3S)-3-hydroxycyclopentyl]amino}[1,3]thiazol[5,4-d]pyrimidin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide;2'-chloro-5'-methoxy-6-methyl-N-{5-[(3R)-3-methylmorpholin-4-yl][1,3]thiazolo[5,4-d]pyrimidin-2-yl} -[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-{5-[(3S)-3-methylmorpholin-4-yl][1,3]thiazolo[5,4-d]pyrimidin-2-yl} -[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-{5-[(propan-2-yl)amino][1,3]thiazolo[5,4-d]pyrimidin-2-yl} -[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-(5-{2-oxa-7-azaspiro[3,5]nonan7-yl}-[1,3]thiazol[5,4-d]pyrimidin-2-yl)-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-(5-{3,8-diazabicyclo[3.2.1]octan-3-yl}[1,3]thiazol[5,4-d]pyrimidin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(piperazin-1-yl)[1,3]thiazol[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(2-oxopyrrolidin-1-yl)-1,3benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(3-oxomorpholin-4-yl)-1,3benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide;2'-chloro-5'-methoxy-6-methyl-N-[6-(3-methyl-2-oxoimidazolidin1-yl)-1,3-benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(2-oxo-1,3-oxazolidin-3-yl)1,3-benzothiazol-2-yl]-[4,4' -bipyridine]-3-carboxamide; Petition 870250080361, of 08 / 09 / 2025, pág. 273 / 513 31 / 37 2'-chloro-5'-methoxy-6-methyl-N-[6-(2-oxoimidazolidin1-yl)-1,3benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(2-oxopiperidin-1-yl)[1,3]thiazol [4,5-c]pyridin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-{[1,3]thiazol[4,5-c]pyridin-2-yl}[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-{6-chloro-[1,3]thiazol[5,4-c]pyridin-2-yl}-5'-methoxy6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-{6-chloro-[1,3]thiazol[4,5-c]pyridin-2-yl}-5'-methoxy6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(morpholin-4-yl)[1,3]thiazol [4,5-c]pyridin-2-yl]-[4,4'-bipyridine]-3-carboxamide;2'-chloro-N -[6-(dimethylsulfamoyl)-1,3-benzothiazol-2-yl] -5'methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(morpholin-4-yl)[1,3]thiazol [4,5-b]pyridin-2-yl]-[4,4' -bipyridine]-3-carboxamide; 2'-chloro-N-[6-(4-hydroxypiperidin-1-yl)-[1,3]thiazol [4,5c]pyridin-2-yl]-5'-methoxy-6-methyl-[4,4' -bipyridine]-3-carboxamide; N-(1,3-benzothiazol-2-yl)-2'-chloro-5' -methoxy-6-methyl-[4,4' -bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(2-oxopiperidin-1-yl)[1,3]thiazol [4,5-b]pyridin-2-yl]-[4,4' -bipyridine]-3-carboxamide; 2'-chloro-N-[6-(4-hydroxypiperidin-1-yl)-[1,3]thiazol[4,5b]pyridin-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(morpholin-4-yl)[1,3]thiazol[5,4-b]pyridin-2-yl]-[4,4' -bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(2-oxopiperidin-1-yl)[1,3]thiazolo[5,4-b]pyridin-2-yl]-[4,4'-bipyridine]-3-carboxamide;2'-chloro-N-[5-(4-hydroxypiperidin-1-yl)-[1,3]thiazol[5,4b]pyridin-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-N-{5-methoxy-[1,3]thiazol[5,4-d]pyrimidin-2yl}-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-(5-{2-oxa-6-azaspiro[3.4]octan6-yl}-[1,3]thiazol[5,4-d]pyrimidin-2-yl)-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N -{5-[(2-hydroxy-2-methylpropyl)amino][1,3]thiazol[5,4-d]pyrimidin-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-{5-[(2-methylpropyl)amino][1,3]thiazol[5,4-d]pyrimidin-2-yl} -[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-[5-(cyclobutylamino)-[1,3]thiazol[5,4-d]pyrimidin-2yl]-5 '-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-N-[5-(4-methoxypiperidin-1-yl)[1,3]thiazol[5,4-d]pyrimidin-2-yl]-6-methyl-[4,4'-bipyridine] -3-carboxamide;2'-chloro-N-(5-{6-hydroxy-2-azaspiro[3.3]heptan-2-yl}[1,3]thiazol[5,4-d]pyrimidin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-(5-{6-oxa-2-azaspiro[3.4]octan2-yl}-[1,3]thiazol[5,4-d]pyrimidin-2-yl)-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N -{6-[imino(methyl)oxo-λ6-sulfanyl]-1,3-benzothiazol-2yl}-5'-methoxy-6-methyl-[4,4'-bipyridine] -3-carboxamide; 2'-chloro-N-[6-(1,1 -dioxo-1 λ6,2-thiazolidin-2-yl)-1,3benzothiazol-2-yl]-5'-methoxy-6-methyl-[4,4' -bipyridine]-3-carboxamide; 2'-chloro-N -{6-[(4R)-4-hydroxy-2-oxopiperidin-1 -yl]-1,3benzothiazol-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[6-(4-methyl-2-oxopiperidin-1-yl)1,3-benzothiazol-2-yl]-[4,4' -bipyridine]-3-carboxamide; 2'-chloro-N-[5-(3,6-dihydro-2H-pyran-4-yl)-[1,3]thiazolo[5,4d]pyrimidin-2-yl]-5'-methoxy-6-methyl- [4,4'-bipyridine]-3-carboxamide;Petition 870250080361, of 08 / 09 / 2025, pág. 275 / 513 33 / 37 N-[5-(4-hydroxypiperidin-1-yl)-[1,3]thiazol[5,4-d]pyrimidin-2-yl]5'-methoxy-6-methyl-2 '-(trifluoromethyl) -[4,4'-bipyridine] -3-carboxamide; N-[5-(4-hydroxypiperidin-1-yl)-[1,3]thiazol[5,4-d]pyrimidin-2-yl]5'-methoxy-6-methyl-2 '-(trifluoromethyl) -[4,4'-bipyridine] -3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(trifluoromethyl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-{5-methyl-[1,3]thiazolo[5,4-d]pyrimidin-2-yl}-[4,4'-bipyridine]-3-carboxamide; 5'-methoxy-2',6-dimethyl-N-[5-(morpholin-4-yl)-[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-fluoro-5 '-methoxy-6-methyl-N -[5-(morpholin-4-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(2-oxopiperidin-1-yl)[1,3]thiazolo[5,4-d]pyrimidin-2-yl]-[4,4'-bipyridine]-3-carboxamide;2'-chloro-N-(5-{[(2R)-2-hydroxypropyl]amino}-[1,3]thiazol[5,4-d ]pyrimidin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-(5-{[(2S)-2-hydroxypropyl]amino}-[1,3]thiazol[5,4-d]pyrimidin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2' -chloro-5' -methoxy-N - [5 -(3 -methoxy-3 -methylazetidin-1yl)- [1,3]thiazol[5,4-d]pyrimidin-2-yl] -6-methyl- [4,4' -bipyridine] -3 -carboxamide; N-(4-bromo-1,3 -benzothiazol-2-yl) -2' -chloro-5' -methoxy-6-methyl- [4,4' -bipyridine]-3 -carboxamide; 2'-chloro-N-{4-[2-(dimethylcarbamoyl)ethyl]-1,3-benzothiazol-2yl} -5' -methoxy-6-methyl- [4,4' -bipyridine] -3 -carboxamide; 2' -chloro-N - [5 - (cyanomethoxy)-1,3 -benzothiazol-2-yl] -5' methoxy-6-methyl- [4,4' -bipyridine] -3 -carboxamide; 2' -chloro-N - {5 - [difluoro(methylcarbamoyl)methoxy] -1,3 -benzothiazol-2-yl} -5' -methoxy-6-methyl- [4,4' -bipyridine] -3-carboxamide;N-(5-bromo-1,3 -benzothiazol-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2' -chloro-N - {5 - [(dimethylcarbamoyl)difluoromethoxy] -1,3 -benzothiazol-2-yl} -5 ' -methoxy-6-methyl- [4,4' -bipyridine] -3-carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(methylcarbamoyl)-1,3-benzothiazol-2-yl] - [4,4' -bipyridine] -3 -carboxamide; 2'-chloro-5'-methoxy-N-(5-methoxy-1,3-benzothiazol-2yl)-6-methyl- [4,4' -bipyridine] -3-carboxamide; 2' -chloro-5' -methoxy-N - {5 -[(2-methoxyethyl)carbamoyl] -1,3 -benzothiazol-2-yl}-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2' -chloro-N - {7 - [(dimethylcarbamoyl)methoxy] - [1,3]thiazol[5,4-d]pyrimidin-2-yl}-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; N-{5-[(1-acetylpiperidin-4-yl)methoxy]-1,3-benzothiazol-2yl} -2' -chloro-5' -methoxy-6-methyl- [4,4' -bipyridine] -3-carboxamide; 2' -chloro-N - {5 - [(dimethylcarbamoyl)methoxy] -1,3 -benzothiazol-2yl} -5' -methoxy-6-methyl- [4,4' -bipyridine] -3-carboxamide;2' -chloro-5' -methoxy-6-methyl-N - {5 -[2-(morpholin-4yl)ethoxy] -1,3 -benzothiazol-2-yl} - [4,4' -bipyridine] -3 -carboxamide; 2'-chloro-5'-methoxy-6-methyl-N - [5-(propan-2yloxy)-1,3 -benzothiazol-2-yl] - [4,4' -bipyridine] -3 -carboxamide; 2' -chloro-N - {5 - [(1,1 -dioxo- 1-Z6-thietan-3 yl)methoxy] - 1,3-benzothiazol-2-yl} -5' -methoxy-6-methyl-[4,4 ' -bipyridine] -3carboxamide; 2' -chloro-N-(5 -ethoxy-1,3 -benzothiazol-2yl)-5 ' -methoxy-6-methyl- [4,4' -bipyridine] -3 -carboxamide; 2'-chloro-5'-methoxy-6-methyl-N- {5-[2-(trifluoromethoxy)ethoxy]-1,3 -benzothiazol-2-yl} - [4,4' -bipyridine] -3 -carboxamide; 2' -chloro-5' -methoxy-N - [6-(3 -methoxyazetidin-1yl)-[1,3]thiazol[4,5-c]pyridin-2-yl]-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-{6-[(2-hidroxi-2-metilpropil)amino]-[1,3]thiazol[4,5 Petição 870250080361, de 08 / 09 / 2025, pág. 277 / 513 35 / 37 -c]pyridin-2-yl}-5'-methoxy-6-metil-[4,4'-bipyridina]-3-carboxamide;2' -chloro-5' -methoxy-N - [6-(3 -methoxy-3 -methylazetidin-1yl)-[1,3]thiazolo[4,5-c]pyridin-2-yl]-6-methyl-[4,4'-bipyridine]-3-carboxamide; 6-[(dimethylcarbamoyl)methyl]-5'-methoxy-N-{[1,3]thiazolo[5,4d]pyrimidin-2-yl} -2' -(trifluoromethyl)- [4,4' -bipyridine] -3 -carboxamide; N-[5-(4-hydroxypiperidin-1-yl)-[1,3]thiazolo[5,4-d]pyrimidin-2yl] - 5' -methoxy-2',6-dimethyl- [4,4' -bipyridine] -3 -carboxamide; 2'-chloro-5'-methoxy-6-methyl-N-[5-(2-oxopiperidin-1yl)-[1,3]thiazolo[5,4-b]pyridin-2-yl]-[4,4'-bipyridine]-3-carboxamide; 5-[(2-{2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-amido}-[1,3]thiazolo[4,5-c]pyridin-6-yl)amino]pentanoic acid; 5-[(2-{2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-amido}-[1,3]thiazolo[5,4-b]pyridin-5-yl)amino]pentanoic acid; 2'-chloro-5'-methoxy-6-methyl-N-{5-[(2H-1,2,3,4-tetrazol-5-yl)methoxy]-1,3-benzothiazol-2-yl}-[4,4'-bipyridine]-3-carboxamide; 2' -chloro-N-(5 -hydroxy-1,3 -benzothiazol-2-yl)-5 ' -methoxy-6-methyl- [4,4' -bipyridine] -3 -carboxamide;2-[(2-{2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-amido}-1,3-benzothiazol5-yl)oxy]ethyl acetate; 2' -chloro-N - [5 -(2-hydroxyethoxy)-1,3 -benzothiazol-2yl] - 5' -methoxy-6-methyl- [4,4' -bipyridine] -3 -carboxamide; 5-(4-hydroxypiperidin-1-yl)-[1,3]thiazol[5,4-d]pyrimidin-2-yl 2'-chloro-5'-methoxy-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-4-carboxylate; 2' -chloro-N - [7-(cyanomethoxy)- [1,3]thiazol[5,4-d]pyrimidin-2yl] - 5' -methoxy-6-methyl- [4,4' -bipyridine] -3 -carboxamide; N-[7-(carbamoylmethoxy)-[1,3]thiazol[5,4-d]pyrimidin-2yl]-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide; 2' -chloro-5' -methoxy-6-methyl-N - [6-(morpholin-3yl)-1,3-benzothiazol-2-yl]-[4,4'-bipyridine]-3-carboxamide; 2'-chloro-N-[5-(4-hydroxypiperidin-1yl)-7-methyl-[1,3]thiazol[5,4-d]pyrimidin-2yl]-5'-methoxy-6-methyl- [4,4' -bipyridine] -3-carboxamide;2'-chloro-N-[5-(2-hydroxy-2-methylpropoxy)-[1,3]thiazol[5,4-d]pyrimidin-2-yl]-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxamide, or a pharmaceutically acceptable salt thereof.

27. Pharmaceutical composition, characterized in that it comprises a compound as defined in any one of claims 1 to 26, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

28. A compound according to any one of claims 1 to 26, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 27, characterized in that it is for use in: (i) therapy; (ii) treatment of a disease distinguished by overexpression of PI; (iii) treatment of cancer; (iv) treatment of a cancer with homologous recombination deficiency (HR); (v) treatment of cancer distinguished by reduced or absent expression of the BRCA gene, absence of the BRCA gene, or reduced function of the BRCA protein; and / or (vi) treatment of lymphoma, rhabdoid tumor, multiple myeloma, uterine cancer, gastric cancer, peripheral nervous system cancer, rhabdomyosarcoma, bone cancer, colorectal cancer, mesothelioma, cancer of Petition 870250080361, dated 08 / 09 / 2025, p.279 / 513 37 / 37 breast cancer, ovarian cancer, lung cancer, fibroblastic cancer, central nervous system cancer, urinary tract cancer, upper aerodigestive tract cancer, leukemia, kidney cancer, skin cancer, esophageal cancer and pancreatic cancer.

29. Method, characterized by being for: (i) treating a disease distinguished by overexpression of PI; (ii) treating cancer; (iii) treating a cancer with homologous recombination deficiency (HR); (iv) treating a cancer distinguished by reduced or absent expression of the BRCA gene, absence of the BRCA gene, or reduced function of the BRCA protein; and / or (v) treating lymphoma, rhabdoid tumor, multiple myeloma, uterine cancer, gastric cancer, peripheral nervous system cancer, rhabdomyosarcoma, bone cancer, colorectal cancer, mesothelioma, breast cancer, ovarian cancer, lung cancer, fibroblastic cancer, central nervous system cancer, urinary tract cancer, upper aerodigestive tract cancer, leukemia, kidney cancer, skin cancer, esophageal cancer, and pancreatic cancer;wherein the method comprises administering to a patient in need of such treatment a therapeutically effective amount of a compound as defined in any one of claims 1 to 26, or a pharmaceutically acceptable salt thereof, or of a pharmaceutical composition as defined in claim 27.