Adenine derivatives as HSP90 inhibitors

Abstract

The present invention relates to compounds of formula (I), or pharmaceutically acceptable salts and / or solvates thereof, wherein X1, X2, Y, L1, R1, R1', R2, R2', n, and A are as defined in the claims, which are useful as inhibitors of HSP90, in particular for the treatment of cancers, neurodegenerative diseases, and neurodegenerative diseases with proteins aggregates such as congenital central hypoventilation syndrome (CCHS).

Description

1 / 79 Adenine derivatives as HSP90 inhibitors Field of Invention

[001] The present invention relates to adenine derivatives, especially compounds of formula (I) as detailed below, which are useful as HSP90 inhibitors, in particular for the treatment of cancers, neurodegenerative diseases and neurodegenerative diseases with protein aggregates such as congenital central hypoventilation syndrome (CCHS). Fundamentals of the Invention

[002] HSP90s (heat shock proteins 90) are a ubiquitous family of ATP-dependent molecular chaperone proteins consisting of four paralogs: Hsp90ae and Hsp90p in the cytosol, Grp94 in the endoplasmic reticulum, and Trap1 in the mitochondria. Dozens of client proteins, including growth factors, signaling kinases, transcription factors, and cell surface receptors, depend on members of the HSP90 family for their conformational maturation, stabilization, and appropriate subcellular localization.

[003] HSP90s orchestrate crucial physiological processes such as cell survival, cell cycle control, hormone signaling, and apoptosis. Conversely, HSP90s and their secreted forms contribute to the development and progression of serious Petition 870250083412, dated 09 / 16 / 2025, page 19 / 105 2 / 79 pathologies, including cancers, neurodegenerative diseases, and neurodegenerative diseases with protein aggregates such as congenital central hypoventilation syndrome (CCHS).

[004] As a result, HSP90 proteins have emerged as an attractive target for the development of treatments for these diseases.

[005] Several HSP90 inhibitors have been developed and tested, such as, for example, Debio0932 (also referred to as CUDC-305, which stands for 2-((6-(dimethylamino)benzo[d][1,3]dioxol-5-yl)thio)-1-(2(neopentylamino)ethyl)-1H-imidazo[4,5-c]pyridin-4-amine). However, despite initial promise, many of these inhibitors have exhibited limited stability, efficacy, and selectivity. For example, HSP90 inhibitors such as Debio0932 exhibit an improvable metabolization profile and thus suboptimal pharmacokinetic properties.

[006] Thus, there is a need for new and improved HSP90 inhibitors with good potency and selectivity and with improved metabolization profiles.

[007] The present invention provides a new class of HSP90 inhibitors that exhibit improved CYP inhibition profiles and microsomal clearance, as detailed in the experimental section.

[008] The new HSP90 inhibitors of the invention have Petition 870250083412, dated 09 / 16 / 2025, p. 20 / 105 3 / 79 potential for the treatment of diseases or disorders in which HSP90 is implicated, such as cancers, neurodegenerative diseases, and neurodegenerative diseases with protein aggregates such as congenital central hypoventilation syndrome (CCHS). Summary

[009] This invention thus relates to a compound of formula (I): (I) or a pharmaceutically acceptable salt and / or solvate thereof, where X1, X2, Y, L1, R1, R1', R2, R2', n, and A are as defined below.

[0010] The invention also relates to a pharmaceutical composition comprising a compound according to the invention or a pharmaceutically acceptable salt and / or solvate thereof and at least one pharmaceutically acceptable carrier.

[0011] The invention further relates to a compound according to the invention or a pharmaceutically acceptable salt and / or solvate thereof, for use as a medicament. Petition 870250083412, dated 09 / 16 / 2025, p. 21 / 105 4 / 79

[0012] The invention also relates to a compound according to the invention or a pharmaceutically acceptable salt and / or solvate thereof, for use in the treatment of cancers, neurodegenerative diseases, neurodegenerative diseases with protein aggregates, infectious diseases, ROHHAD (Rapid Onset Obesity with Hypothalamic Dysfunction, Hypoventilation and Autonomic Dysregulation), diabetic atherosclerosis, severe psoriasis, primary myelofibrosis and acute pancreatitis.

[0013] In one embodiment, cancer is selected from among brain tumors, hematopoietic disorders, breast cancer, lung cancer, leukemia, lymphoma, pancreatic cancer, multiple myeloma, prostate cancer, glioma, colon cancer, gastric cancer, ovarian cancer, and any cancer with oncogene production controlled by HSP90.

[0014] In one embodiment, the neurodegenerative disease is selected from among Alzheimer's disease, senile dementia of the Alzheimer type, dementia due to head trauma and diffuse brain damage, pugilistic dementia, frontal lobe dementia, Pick's disease, Huntington's disease, multiple system atrophy combining dementia with ataxia and / or manifestations of Parkinson's disease, progressive supranuclear palsy, diffuse Lewy body disease, corticobasal degeneration, Hallervorden-Spatz disease, Petition 870250083412, dated 09 / 16 / 2025, page 22 / 105 5 / 79 progressive familial myoclonic epilepsy, Parkinson's disease, striatonigral degeneration, progressive supranuclear palsy, torsion dystonia, spasmodic torticollis, familial tremor, Gilles de la Tourette syndrome, cerebellar cortical degeneration, olivopontocerebellar atrophy, spinocerebellar degeneration, Shy-Drager syndrome, amyotrophic lateral sclerosis, spinal muscular atrophy, spinal and bulbar muscular atrophy (Kennedy's disease), primary lateral sclerosis, hereditary spastic paraplegia, neural muscular atrophy, chronic familial polyneuropathies, peroneal muscular atrophy, hypertrophic interstitial polyneuropathy, retinitis pigmentosa, hereditary optic atrophy, and Leber amaurosis.

[0015] In one embodiment, the neurodegenerative disease with protein aggregates is selected from congenital central hypoventilation syndrome (CCHS), Huntington's disease (HTT), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), synucleinopathies, and central hypoventilation syndrome (CHS). Definitions

[0016] The definitions and explanations below are for the terms as used throughout the application, including both the descriptive report and the claims. When describing the compounds of the invention, the terms used should be Petition 870250083412, dated 09 / 16 / 2025, page 23 / 105 6 / 79 interpreted according to the following definitions, unless otherwise indicated.

[0017] Where chemical substituents are combinations of chemical groups, the point of attachment of the substituent to the molecule is by the last chemical group mentioned. For example, a cycloalkyl substituent is attached to the rest of the molecule through the alkyl portion and it can be represented as follows: -alkyl-cycloalkyl.

[0018] In the present invention, the following terms have the following meanings:

[0019] Alkyl, by itself or as part of another substituent, refers to a hydrocarbyl radical of the formula CnH2n+i where n is a number greater than or equal to 1. Generally, the alkyl groups of this invention comprise from 1 to 12 carbon atoms, from 1 to 6 carbon atoms, or preferably from 1 to 4 carbon atoms. The alkyl groups may be linear or branched and may be substituted as indicated herein. The alkyl groups may be linear or branched and may be substituted as indicated herein. Non-limiting examples of alkyl groups include methyl, ethyl, propyl (n-propyl, i-propyl), butyl (n-butyl, i-butyl, s-butyl and t-butyl), pentyl and its isomers (e.g., n-pentyl, iso-pentyl), and hexyl and its isomers (e.g., n-hexyl, iso-hexyl).

[0020] Alkenyl refers to a hydrocarbyl group Petition 870250083412, dated 09 / 16 / 2025, p. 24 / 105 7 / 79 unsaturated, which may be linear or branched, comprising one or more carbon-carbon double bonds. Suitable alkenyl groups comprise 2 to 6 carbon atoms, preferably between 2 and 4 carbon atoms, and even more preferably between 2 and 3 carbon atoms. Examples of alkenyl groups are ethenyl, 2-propenyl (allyl), 2-butenyl, 3-butenyl, 2-pentenyl and their isomers, 2-hexenyl and its isomers, 2,4-pentadienyl and the like.

[0021] Aminocarbonylalkyl refers to any -alkyl-(C=O)-NH2 group, wherein the alkyl is as defined above.

[0022] Cyanoalkyl refers to any alkyl-CN group, wherein the alkyl is as defined above.

[0023] Cyanocarbonyl refers to a -(C=O)CN group.

[0024] Cycloalkyl, by itself or as part of another substituent, refers to a cyclic alkyl group, that is, a monovalent hydrocarbyl group, saturated or unsaturated having one or two cyclic structures. Cycloalkyl includes monocyclic or bicyclic hydrocarbyl groups. Cycloalkyl groups may comprise three or more carbon atoms in the ring and, generally according to this invention, comprise from three to ten carbon atoms, more preferably from three to eight carbon atoms, even more preferably from three to six. Petition 870250083412, dated 09 / 16 / 2025, p. 25 / 105 8 / 79 carbon atoms. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0025] Cycloalkylalkyl refers to any -alkyl-cycloalkyl group, wherein the alkyl and cycloalkyl are as defined above.

[0026] Halogen or halo means fluorine, chlorine, bromine or iodine. Generally, the halo groups of this invention are fluorine, chlorine or bromine, preferably fluorine.

[0027] Haloalkyl, by itself or as part of another substituent, refers to an alkyl radical having the meaning as defined above in which one or more hydrogens are replaced by a halogen as defined above. Non-limiting examples of such haloalkyl radicals include chloromethyl, 1-bromoethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1,1-difluoroethyl, 1,1,1-trifluoroethyl and the like.

[0028] Heterocyclic, by itself or as part of another substituent, refers to non-aromatic cyclic groups, fully saturated or partially unsaturated (e.g., monocyclic groups of 3 to 7 elements, bicyclic groups of 7 to 11 elements, or containing a total of 3 to 10 atoms in the ring) having at least one heteroatom in at least one ring containing carbon atoms. Heterocyclic groups may be particular for groups of 3 to 7 elements, of Petition 870250083412, dated 09 / 16 / 2025, p. 26 / 105 9 / 79 A preferred mode, of 5 or 6 elements. Heterocyclic groups in particular may be monocyclic or bicyclic, preferably monocyclic. Each ring of the heterocyclic group containing a heteroatom may have 1, 2, 3 or 4 heteroatoms selected from nitrogen, oxygen and / or sulfur atoms, where the nitrogen and sulfur heteroatoms may optionally be oxidized and the nitrogen heteroatoms may optionally be quaternized. Any of the carbon atoms of the heterocyclic group may be substituted by oxo (e.g., piperidone, pyrrolidinone). The heterocyclic group may be attached to any heteroatom or carbon atom of the ring or ring system, where valence permits. Heterocyclic rings with multiple rings may be fused, bridged and / or joined through one or more spiro atoms.Exemplary non-limiting heterocyclic groups include oxetanyl, piperidinyl, azetidinyl, 2-imidazolinyl, pyrazolidinylimidazolidinyl, isoxazolinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, piperidinyl, 3H-indolyl, indolinyl, isoindolinyl, 2-oxopiperazinyl, piperazinyl, homopiperazinyl, 2pyrazolinyl, 3-pyrazolinyl, tetrahydro-2H-pyranyl, 2Hpyranyl, 4H-pyranyl, 3,4-dihydro-2H-pyranyl, 3dioxolanyl, 1,4-dioxanyl, 2,5-dioximidazolidinyl, 2. Petition 870250083412, de 16 / 09 / 2025, pág. 27 / 105 10 / 79 oxopiperidinila, 2-oxopyrrolodinila, indolinila, tetrahydropyranila, tetra-hidrofuranila, tetra-hidroquinolinila, tetra-hidroisoquinolin-1-ila, tetra-hidroisoquinolin-2-ila, tetra-hidroisoquinolin-3-ila, tetra-hidroisoquinolin-4-ila, thiomorpholin-4-yl, thiomorpholin-4-ylsulfonate, 1,3-dioxolanila, 1,4-oxatianila, 1H pyrrolizinila, tetra-hidro-1,1-dioxothiofenila, N -formylpiperazinila and morpholin-4-ila.

[0029] Heterocyclylalkyl refers to any -alkyl-heterocyclyl group, wherein the alkyl and heterocyclyl are as defined above.

[0030] Pharmaceutically acceptable means that the component is not harmful to the individual to whom it is administered and is compatible with all other components administered together.

[0031] A pharmaceutically acceptable carrier refers to an excipient that does not produce an adverse, allergic, or other undesirable reaction when administered to an animal, or preferably a human being. This includes any and all solvents, dispersing media, coatings, antibacterial and antifungal agents, isotonic and absorption retardants, and the like. For human administration, preparations must satisfy sterility, pyrogenicity, general safety and purity standards as required by regulatory bodies. Petition 870250083412, dated 09 / 16 / 2025, page 28 / 105 11 / 79, such as the FDA or EMA office.

[0032] Prodrug as used herein means the pharmacologically acceptable derivatives of the compounds of the invention, the in vivo biotransformation product of which is the active drug. Prodrugs are distinguished by increased bioavailability and are readily metabolized into the active compounds in vivo. Suitable prodrugs for the purpose of the invention include carboxylic esters, in particular alkyl esters, aryl esters, acyloxyalkyl esters and dioxolene carboxylic esters; ascorbic acid esters.

[0033] Solvate is used herein to describe a molecular complex comprising a compound of the invention and containing stoichiometric or substoichiometric amounts of one or more molecules of a pharmaceutically acceptable solvent such as ethanol. The term hydrate refers to when said solvent is water.

[0034] Administration or a variant thereof (e.g., administer) means to provide the active agent or active ingredient, alone or as part of a pharmaceutically acceptable composition, to an individual in need thereof.

[0035] Individual refers to a mammal, preferably a human being. According to the present invention, an individual is a mammal, preferably, Petition 870250083412, dated 09 / 16 / 2025, page 29 / 105 12 / 79 a human being who suffers from the target disease and / or who is prone to developing the target disease. In one embodiment, the individual is a “patient,” that is, a mammal, preferably a human being, who is expecting or is receiving medical assistance or was / is / will be the subject of a medical procedure or is monitored for the development of the target disease.

[0036] “Therapeutically acceptable amount” (or more simply an “effective amount”) as used herein refers to the amount of active agent or active ingredient that is targeted without causing significant negative or adverse side effects to the individual in need of treatment, prevention, reduction, relief or delay (attenuation) of one or more of the symptoms of the target disease.

[0037] “Treat” or “treatment” refers to a therapeutic treatment, a prophylactic (or preventive) treatment, or both a therapeutic and a prophylactic (or preventive) treatment, where the objective is to prevent, reduce, alleviate, and / or delay (attenuate) one or more of the symptoms of the target disease in an individual in need of treatment. Those in need of treatment include those already with the disorder as well as those likely to have the disorder or those in whom the disorder should be prevented. Detailed Description Petition 870250083412, dated 09 / 16 / 2025, p. 30 / 105 13 / 79 Compounds

[0038] This invention relates to a compound of formula (I) (I) or a pharmaceutically acceptable salt and / or solvate thereof, wherein: X1 is N or CH; X2 is N or CH; provided that X1 and X2 are not both N; Y is S, SO, SO2, NH, O or CH2; L1 is a C1-4 alkyl group; R1 is a C1-8 alkyl group; R1' is H or C1-4 alkyl; n equals 1 or 2. R2e R2' are each independently H, D, methyl or halo; A is NR3R3', OR3 or SO2R3; where: R3 is cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, alkenyl, C1-4 haloalkyl, cyanoalkyl, cyanocarbonyl, aminocarbonylalkyl; in which the cycloalkyl and Petition 870250083412, dated 09 / 16 / 2025, p. 31 / 105 14 / 79 heterocyclyl groups are optionally substituted with one or more substituents selected from D, cyano, halo, hydroxyl, and C1-4 alkyl; R3' is C1-4 alkyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, alkenyl, C1-4 haloalkyl, cyanoalkyl, cyanocarbonyl, aminocarbonylalkyl; wherein the cycloalkyl and heterocyclyl moieties are optionally substituted by one or more substituents selected from D, cyano, halo, hydroxyl, and C1-4 alkyl; preferably, R3' is methyl.

[0039] In one embodiment, X1 and X2 are both CH or X1 is N and X2 is CH. In one embodiment, X1 and X2 are both CH. In another embodiment, X1 is N and X2 is CH.

[0040] In one embodiment, L1 is ethyl. In one embodiment, R1 is a C5 alkyl, preferably neopentyl. In one embodiment, R1' is H. In a specific embodiment, L1 is ethyl, R1 is neopentyl and R1' is H.

[0041] In a preferred embodiment, Y is S, SO or NH; in a preferred mode, Y is S.

[0042] In one modality, n equals 1.

[0043] In one embodiment, R2 and R2' are both H, both F, both D, or both methyl. In one embodiment, one of R2 and R2' is F, D, or methyl and the other is H. In one embodiment, R2 and R2' are both H or both F. Petition 870250083412, dated 09 / 16 / 2025, p. 32 / 105 15 / 79

[0044] In a specific embodiment, n equals 1, and R2 and R2' are either both H or both F.

[0045] In one embodiment, A is NR3R3', OR3 or SO2R3.

[0046] In a preferred embodiment, R3 is cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, alkenyl or C1-4 haloalkyl. In a preferred embodiment, R3 is cycloalkyl, cycloalkylalkyl, alkenyl or C1-4 haloalkyl.

[0047] In a preferred embodiment, R3' is C1-4 alkyl; in more than one preferred embodiment, R3' is methyl.

[0048] In one embodiment, R3 is from formula (i): R4R4, . ,R(i) where Z is CH or N; Each R4 is independently H, D, cyano, halo, hydroxyl, or C1-4 alkyl; m equals 0, 1, 2, or 3; p is equal to 1, 2, 3, or 4; and represents the point of attachment to the rest of the compound.

[0049] In one embodiment, in formula (i), Z is CH, m equals 0 or 1, ep equals 1 or 2. In an exemplary embodiment, the portion of formula (i) is selected from cyclobutyl and cyclopropylmethyl. Petition 870250083412, dated 09 / 16 / 2025, p. 33 / 105 16 / 79

[0050] In another embodiment, R3 is alkenyl; in a preferred form, R3 is allyl.

[0051] In another embodiment, R3 is a C1-4 haloalkyl; preferably, R3 is difluoroethyl.

[0052] In one embodiment, R3' is methyl.

[0053] In a particular embodiment, A is NR3R3'. In a preferred embodiment, A is NR3R3' wherein R3 is cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, alkenyl or C1-4 haloalkyl; and R3' is C1-4 alkyl. In another preferred embodiment, A is NR3R3' wherein R3 is cycloalkyl, cycloalkylalkyl, alkenyl or C1-4 haloalkyl; and R3' is methyl. In a preferred embodiment, A is NR3R3' wherein R3 is of formula (i) as defined above, alkenyl or C1-4 haloalkyl; and R3' is methyl. In a specific embodiment, A is NR3R3' wherein R3 is of formula (i) as defined above and R3' is methyl. In another specific embodiment, A is NR3R3' where R3 is an alkenyl, preferably an allyl, and R3' is a methyl. In another specific embodiment, A is NR3R3' where R3 is a C1-4 haloalkyl, preferably a difluoroethyl, and R3' is a methyl.

[0054] In one embodiment, the compounds of the invention are of formula (Ia): Petition 870250083412, dated 09 / 16 / 2025, p. 34 / 105 17 / 79 (Ia) or a pharmaceutically acceptable salt and / or solvate thereof, where X1, X2, Y, L1, R1, R1', R2, R2', R3', R4, n, m, ep are as defined above.

[0055] In one embodiment, the compounds of the invention are of formula (Ib): (Ib) or a pharmaceutically acceptable salt and / or solvate thereof, where X1, X2, Y, L1, R1, R1', R2, R2', R3' and n are as defined above.

[0056] According to one embodiment, the compound according to the invention is selected from those listed in Table 1: Table 1 01 <XI A 1 Γ T z^zJ 2-((6- ((ciclopropilmetil)(metil)amino)benzo[ d][1,3]dioxol-5-il)tio)-1-(2- (neopentilamino)etil)-1H-imidazo[4,5c]piridin-4-amina Petition 870250083412, dated 09 / 16 / 2025, p. 35 / 105 18 / 79 02 z^Vz Η' v xx > 8-((6- ((cyclopropyl·methyl)(methyl)amino)benzo[ d][1,3]dioxol-5-yl)thio)-9-(2- (neophentylamino)ethyl)-9H-purin-6-amine 03 o^o nh2 nH2 n^A n^n ^n. HN^ 8-((6- (allyl(methyl)amino)benzo[d][1,3]dioxol5-yl)thio)-9-(2-(neopentalamino)ethyl)- 9H-purine-6-amine 04 y ozO nh2 )r\ Η 1 A Nn^n / \= HNX 8-((6-(allyl(methyl)amino)-2,2- difluorobenzo[d][1,3]dioxol-5-yl)thio)9-(2-(neopentalamino)ethyl)-9H-purine-6amine 05 ( / o nh2NAyN >=< II J As / \—FF HN-2 ((2,2-2) difluoroethyl)(methyl)amino)benzo[d][1,3 ]dioxol-5-yl)thio)-1- (2- (neophentylamino)ethyl)-1H-imidazo[4,5- c]pyridine-4-amine 06 / > < XI Λ rx 1 Γ i í-15 2-(6-(6) (cyclobutyl(methyl)amino)benzo[d][1,3]d ioxol-5-yl)thio)-1-(2- (neophentylamino)ethyl)-1H-imidazo[4,5c]pyridine-4-amine and pharmaceutically acceptable salts and / or solvates of the same .

[0063] The compounds in Table 1 were named using ChemDraw® Ultra 12.0. acquired from CambridgeSoft (Cambridge, MA, USA). Petition 870250083412, dated 09 / 16 / 2025, p. 36 / 105 19 / 79

[0064] All references to compounds of formula (I) include references to salts, solvates, multicomponent complexes and / or liquid crystals thereof. All references to compounds of formula (I) include references to polymorphs and / or crystal habits thereof. All references to compounds of formula (I) include references to pharmaceutically acceptable prodrugs thereof.

[0065] The compounds of formula (I) and their subformulas may contain asymmetric center(s) and thus may exist as different stereoisomeric forms. Consequently, all references to the compounds of formula (I) include references to all possible stereoisomers and include not only racemic compounds but also individual enantiomers and their non-racemic mixtures. When a compound is desired as a single enantiomer, such a single enantiomer may be obtained by stereospecific synthesis, by resolution of the final product or any convenient intermediate, or by chiral chromatographic methods as are each known in the art. Resolution of the final product, an intermediate, or a starting material may be carried out by any suitable method known in the art.

[0066] The bonds of an asymmetric carbon in compounds are generally described using a line. Petition 870250083412, dated 09 / 16 / 2025, p. 37 / 105 20 / 79 continuous (), a continuous wedge ( ) or a dotted wedge .............. It is understood that the use of a continuous or dotted wedge to describe the bonding of an asymmetric carbon atom indicates that only the stereoisomer shown should be included. It is understood that the use of a solid line to describe the bonding of an asymmetric carbon atom indicates that all possible stereoisomers should be included, unless it is clear from the context that a specific stereoisomer is intended.

[0067] All references to compounds of formula (I) include references to isotopically labeled compounds of formula (I), including deuterated compounds of formula (I).

[0068] The compounds of the invention may be in the form of pharmaceutically acceptable salts. The pharmaceutically acceptable salts of the compounds of formula (I) include the acid and base addition salts thereof.

[0069] Suitable acid addition salts are formed from acids that form non-toxic salts. Examples include acetate, adipate, ammonium, aspartate, benzenesulfonate, benzoate, besylate, bicarbonate / carbonate, bisulfate / sulfate, bitartrate / tartrate, borate, bromide, calcium edetate, camsylate, chloride, citrate, clavulanate, cyclamate salts, Petition 870250083412, dated 09 / 16 / 2025, page 38 / 105 21 / 79 dihydrochloride, edetate, edisilate, estolate, hexilate, formate, fumarate, gluceptate, gluconate, glucuronate, glutamate, glycolylarsanilate, hexafluorophosphate, hexylresorcinate, hibenzate, hydrochloride / chlorethum, hidrabamine, hydrobromide / brometho, iodihydrate / iodetum, hidroxinaphthoate, isethionate, lactate, lactobionate, laurate, malate, maleate, malonate, mandelate, mesylate, methyl bromethoate, N-methylglucamine, methylnitrate, methylsulfate, mucate, naphthylate, napsylate, nicotinate, nitrate, oleate, orotate, oxalate, palmitate, pamoate, pantothenate, phosphate / hhydrogen phosphate / di-hydrogen phosphate, polygalacturonate, pyroglutamate, saccharate, salicylate, estearate, succinate, sulfate, subacetate, thanate, theoclate, tosylate, triethiodetox, trifluoroacetate, valerate, hexofoate.

[0070] Basic salts are formed from bases that form non-toxic salts. Examples include aluminum salts, ammonia, arginine, benzathine, N-benzylphenethylamine, calcium, choline, chloroprocaine, N,N'-dibenzylethylenediamine, diethanolamine, diethylamine, 2-(diethylamino)ethanol, diolamine, ethylenediamine, ethanolamine, glycine, 4-(2-hydroxyethyl)morpholine, lithium, lysine, magnesium, meglumine, N-methylglutamine, morpholine, olamine, ornithine, potassium, piperazine, procaine, sodium, tetramethylammonium hydroxide, Petition 870250083412, dated 09 / 16 / 2025, page 39 / 105 22 / 79 tris(hydroxymethyl)aminomethane, tromethamine and zinc.

[0071] Hemissals of acids and bases can also be formed, for example, hemisulfate and hemicalcium salts.

[0072] When the compounds of formula (I) contain an acid group as well as a basic group, the compounds of the invention can also form internal salts and such compounds are within the scope of the invention. When the compounds of the invention contain a hydrogen-donating heteroatom (e.g., NH), the invention also covers salts and / or isomers formed by the transfer of said hydrogen atom to a basic group or atom within the molecule.

[0073] Pharmaceutically acceptable salts of the compounds of formula (I) may be prepared by one or more of these methods: (i) by the reaction of the compound of formula (I) with the desired acid; (ii) by the reaction of the compound of formula (I) with the desired base; (iii) by removing an acid- or base-labile protecting group from a suitable precursor of the compound of formula (I) or by ring-opening a suitable cyclic precursor, for example, a lactone or lactam, using the desired acid; and / or (iv) by converting a salt of the compound of formula (I) into another by reaction with an appropriate acid or by Petition 870250083412, dated 09 / 16 / 2025, page 40 / 105 23 / 79 in the middle of a suitable ion exchange column.

[0074] All these reactions are typically carried out in solution. The salt may precipitate from the solution and be collected by filtration or it may be recovered by evaporation of the solvent. The degree of ionization in the salt can vary from completely ionized to nearly non-ionized.

[0075] Although, generally, with regard to the salts of the compounds of the invention, pharmaceutically acceptable salts are preferred, it should be noted that the invention in its broadest sense also included non-pharmaceutically acceptable salts, which, for example, can be used in the isolation and / or purification of the compounds of the invention. For example, salts formed with optically active acids or bases can be used to form diastereomeric salts that can facilitate the separation of optically active isomers of the compounds of formula (I) above. Manufacturing Process

[0076] The compound of the invention can be synthesized by methods known in the art. In particular, the compound of the invention can be synthesized by the methods detailed in the experimental section below. Pharmaceutical Composition

[0077] This invention also relates to a pharmaceutical composition comprising a compound according to Petition 870250083412, dated 09 / 16 / 2025, page 41 / 105 24 / 79 invention, as described above, and at least one pharmaceutically acceptable carrier.

[0078] According to a first embodiment, the pharmaceutical composition comprises the compound according to the invention as the sole therapeutic agent.

[0079] According to a second embodiment, the pharmaceutical composition additionally comprises at least one other therapeutic agent. In one embodiment, the other therapeutic agent is selected from among the therapeutic agents detailed below related to combination therapy.

[0080] The pharmaceutical composition of the invention may additionally comprise therapeutically active compounds other than those listed herein, which are commonly used in the treatment of the target pathological conditions. Medical Use and Treatment Methods

[0081] This invention also relates to a compound according to the invention, as described above, for use as a medicament.

[0082] This invention also relates to a compound according to the invention, as described above, for use as an HSP90 inhibitor.

[0083] The compounds of the invention are advantageously specific HSP90 inhibitors. In some embodiments, the compounds of the invention are selective HSP90 inhibitors. Petition 870250083412, dated 09 / 16 / 2025, p. 42 / 105 25 / 79 alpha with respect to HSP90 beta. In some embodiments, the compounds of the invention are selective inhibitors of HSP90 alpha with respect to the other three HSP90 paralogs (HSP90 beta, Grp94 and Trap-1).

[0084] In some embodiments, the compounds of the invention exhibit improved penetration into the brain compared to other HSP90 inhibitors.

[0085] This invention also relates to a compound according to the invention, as described above, for use in the treatment of a disease or disorder in which HSP90 is implicated. Examples of diseases or disorders in which HSP90 is implicated include cancers, neurodegenerative diseases, neurodegenerative diseases with protein aggregates, infectious diseases, ROHHAD (Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation and Autonomic Dysregulation), diabetic atherosclerosis, severe psoriasis, primary myelofibrosis, and acute pancreatitis.

[0086] In one embodiment, the invention provides a compound according to the invention, as described above, for use in the treatment of cancers, neurodegenerative diseases, neurodegenerative diseases with protein aggregates, infectious diseases, ROHHAD, diabetic atherosclerosis, severe psoriasis, primary myelofibrosis and acute pancreatitis.

[0087] The invention thus provides a compound accordingly Petition 870250083412, dated 09 / 16 / 2025, page 43 / 105 26 / 79 with the invention, as described above, for use in the treatment of cancer. In one particular embodiment, the cancer is human cancer. In one embodiment, the cancer is solid cancer. In another embodiment, the cancer is non-solid cancer.

[0088] Examples of cancers include, but are not limited to, brain tumors, hematopoietic disorders, breast cancer, lung cancer, leukemia, lymphoma, pancreatic cancer, multiple myeloma, prostate cancer, glioma, colon cancer, gastric cancer, ovarian cancer, and any cancer with oncogene production controlled by HSP90. The term "cancer with oncogene production controlled by HSP90" here refers to cancers triggered by oncogenic proteins that are clients of HSP90, where the oncogenic proteins are, for example, selected from v-Src, Lyn, Lck, Yes, Fps, Fes, Bcr-Abl, Raf-1, AKT / PKB, ErbB2, Plk-1, MET, Wee1, Cdc2, Cdc4, Cdc6, Dnmt-1, Survivin, Mutant p53, c-Myc, hTERT, MOK, MAK, MRK, DNA polymerase α, estrogen receptor, androgen receptor, HIF-1a, SV40 large T antigen and SV40 small T antigen; and oncogenic translocations such as AlkNPM or Alk-EML4.

[0089] The present invention also provides a compound according to the invention, as described above, for use in the treatment of a neurodegenerative disease. Petition 870250083412, dated 09 / 16 / 2025, p. 44 / 105 27 / 79

[0090] Examples of neurodegenerative diseases include, but are not limited to, Alzheimer's disease, senile dementia of the Alzheimer type, dementia due to head trauma and diffuse brain damage, pugilistic dementia, frontal lobe dementia, Pick's disease, Huntington's disease, multiple system atrophy combining dementia with ataxia and / or manifestations of Parkinson's disease, progressive supranuclear palsy, diffuse Lewy body disease, corticobasal degeneration, Hallervorden-Spatz disease, progressive familial myoclonic epilepsy, Parkinson's disease, striatonigral degeneration, progressive supranuclear palsy, torsion dystonia, spasmodic torticollis, familial tremor, Gilles de la Tourette syndrome, cerebellar cortical degeneration, olivopontocerebellar atrophy, spinocerebellar degeneration, Shy-Drager syndrome, amyotrophic lateral sclerosis, muscular atrophy spinal muscular atrophy, spinal and bulbar muscular atrophy (Kennedy's disease), primary lateral sclerosis,Hereditary spastic paraplegia, neural muscular atrophy, chronic familial polyneuropathies, peroneal muscular atrophy, hypertrophic interstitial polyneuropathy, retinitis pigmentosa, hereditary optic atrophy, and Leber amaurosis.

[0091] The present invention also provides a compound according to the invention, as described above, for use in Petition 870250083412, dated 09 / 16 / 2025, page 45 / 105 28 / 79 treatment of a neurodegenerative disease with protein aggregates.

[0092] Examples of neurodegenerative diseases with protein aggregates include, but are not limited to, congenital central hypoventilation syndrome (CCHS), Huntington's disease (HTT), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), alpha-synucleinopathies, and central hypoventilation syndrome (CHS).

[0093] In particular, the invention provides a compound according to the invention, as described above, for use in the treatment of congenital central hypoventilation syndrome (CCHS). The terms “congenital central hypoventilation syndrome,” “CCHS,” “Ondine’s syndrome,” “congenital failure of autonomic control,” “Haddad’s syndrome,” and “Ondine-Hirschsprung disease” are equivalent and refer to a rare neurocristopathy distinguished by the absence of adequate autonomic control of respiration with decreased sensitivity to hypoxia and hypercapnia. Congenital central hypoventilation syndrome is distinguished by sleep hypoventilation associated with dysfunction of CO2 / H+-sensitive PHOX2B neurons of the retrotrapezoidal nucleus / parafacial respiratory group (RTN / pFRG). Patients are therefore deprived of the interoceptive alarms that normally trigger awakening in cases of life-threatening hypoxia during sleep and in Petition 870250083412, dated 09 / 16 / 2025, page 46 / 105 29 / 79 subjects are more severely affected, also during waking hours. Congenital central hypoventilation syndrome is associated with malfunction of the nerves that control involuntary bodily functions and abnormal development of the early embryonic cells that form the spinal cord. The hypercapnia, acidosis, and hypoxemia resulting from CCHS negatively affect physiological functions and can be fatal.

[0094] The present invention also provides a compound according to the invention, as described above, for use in the treatment of an infectious disease.

[0095] Examples of infectious diseases include, but are not limited to, viral infections such as Enterovirus 71 (EV71) infection, other viruses in the picornavirus family, or COVID-19; and protozoan (Plasmodium) infections such as Malaria.

[0096] This invention also relates to the use of a compound according to the invention, as described above, in the manufacture of a medicament to inhibit HSP90.

[0097] This invention also relates to the use of a compound according to the invention, as described above, in the manufacture of a medicament for the treatment of a disease or disorder in which HSP90 is implicated, as defined above.

[0098] In one embodiment, the invention provides the use of a Petition 870250083412, dated 09 / 16 / 2025, page 47 / 105 30 / 79 compound according to the invention, as described above, in the manufacture of a medicament for the treatment of cancers, neurodegenerative diseases, neurodegenerative diseases with protein aggregates, infectious diseases, ROHHAD, diabetic atherosclerosis, severe psoriasis, primary myelofibrosis and acute pancreatitis.

[0099] The invention thus provides the use of a compound according to the invention, as described above, in the manufacture of a medicament for the treatment of cancer, as defined above.

[00100] The invention also provides for the use of a compound according to the invention, as described above, in the manufacture of a medicament for the treatment of a neurodegenerative disease, as defined above.

[00101] The invention also provides the use of a compound according to the invention, as described above, in the manufacture of a medicament for the treatment of a neurodegenerative disease with protein aggregates, as defined above. In particular, the invention provides the use of a compound according to the invention, as described above, in the manufacture of a medicament for the treatment of congenital central hypoventilation syndrome (CCHS).

[00102] The invention also provides the use of a compound according to the invention, as described above, in the manufacture of a medicament for the treatment of a Petition 870250083412, dated 09 / 16 / 2025, page 48 / 105 31 / 79 infectious disease, as defined above.

[00103] This invention also relates to a method of inhibiting HSP90 in an individual in need thereof, comprising a step of administering to said individual a therapeutically acceptable amount of a compound according to the invention, as described above.

[00104] This invention also relates to a method for treating a disease or disorder in which HSP90 is implicated, in an individual in need thereof, comprising a step of administering to said individual a therapeutically acceptable amount of a compound according to the invention, as described above.

[00105] This invention also relates to a method for treating cancers, neurodegenerative diseases, neurodegenerative diseases with protein aggregates, infectious diseases, ROHHAD, diabetic atherosclerosis, severe psoriasis, primary myelofibrosis and acute pancreatitis, in an individual in need thereof, comprising a step of administering to said individual a therapeutically acceptable amount of a compound according to the invention, as described above.

[00106] This invention also relates to a method for treating cancer in an individual in need thereof, comprising a step of administering to said individual a quantity Petition 870250083412, dated 09 / 16 / 2025, page 49 / 105 32 / 79 therapeutically acceptable of a compound according to the invention, as described above.

[00107] This invention also relates to a method for treating a neurodegenerative disease in an individual in need thereof, comprising a step of administering to said individual a therapeutically acceptable amount of a compound according to the invention, as described above.

[00108] This invention also relates to a method for treating a neurodegenerative disease with protein aggregates in an individual in need thereof, comprising a step of administering to said individual a therapeutically acceptable amount of a compound according to the invention, as described above. In particular, this invention relates to a method for treating congenital central hypoventilation syndrome (CCHS) in an individual in need thereof, comprising a step of administering to said individual a therapeutically acceptable amount of a compound according to the invention.

[00109] This invention also relates to a method for treating an infectious disease in an individual in need thereof, comprising a step of administering to said individual a therapeutically acceptable amount of a compound according to Petition 870250083412, dated 09 / 16 / 2025, page 50 / 105 33 / 79 invention, as described above.

[00110] According to one embodiment, the compound according to the invention is administered to the individual as the sole therapeutic agent.

[00111] According to another embodiment, the compound according to the invention is administered to the individual in combination with at least one other therapeutic agent.

[00112] According to one embodiment, the compound according to the invention is administered to the individual in combination with at least one other therapeutic agent that is beneficial for the disease being treated.

[00113] In one embodiment, the other therapeutic agent may be selected from a second anticancer therapy, such as chemotherapy, immunotherapy, cell therapy and / or any anticancer agent currently in clinical use or in clinical trials.

[00114] According to one embodiment, the compound according to the invention can be administered in combination with conventional surgery, radiotherapy or transplantation, and / or with at least one other therapeutic agent as mentioned above.

[00115] Such combined treatments can be achieved through simultaneous, sequential, or separate dosing of the individual treatment components. Such combined products employ the compounds of the invention. Petition 870250083412, dated 09 / 16 / 2025, page 51 / 105 34 / 79 within the dosage range described herein and the other therapeutic agent within its appropriate dosage range.

[00116] In the context of the present invention, the term “combination” preferably means a combined occurrence of the compound according to the invention and an additional therapeutic agent. Therefore, the combination may occur as a composition, comprising all the components in one and the same mixture (e.g., a pharmaceutical composition) or it may occur as a kit of parts, wherein different components form different parts of such a kit of parts. Administration of the compound according to the invention and the additional therapeutic agent may occur either simultaneously or temporally staggered, with similar or different administration times (i.e., similar or different numbers of administrations of each component), either at the same administration site or at different administration sites, in similar or different dosage forms.

[00117] The compounds of the invention can be administered orally, parenterally (e.g., intramuscular, intraperitoneal, intravenous, intracerebroventricular, intracisternal, subcutaneous injection or implant), by inhalation spray, nasal, vaginal, rectal, sublingual or topical routes of administration and can be formulated in unit formulations of Petition 870250083412, dated 09 / 16 / 2025, page 52 / 105 35 / 79 appropriate dosages containing conventional, non-toxic, and pharmaceutically acceptable carriers, adjuvants, and vehicles suitable for each route of administration.

[00118] Pharmaceutical compositions for administering the compounds of this invention can conveniently be presented in the form of dosage units and can be prepared by any of the methods well-known in the pharmaceutical art. All methods include the step of placing the active ingredient in association with the carrier, which constitutes one or more accessory ingredients. In general, pharmaceutical compositions are prepared by uniformly and intimately placing the active ingredient in association with a liquid carrier or a finely divided solid carrier, or both, and then, if necessary, molding the product into the desired formulation. In the pharmaceutical composition, the active ingredient is included in a sufficient quantity to produce the desired effect on the disease process or condition.As used herein, the term "composition" is intended to encompass a product comprising the specified ingredients in the specified quantities, as well as any product that results directly or indirectly from the combination of the specified ingredients in the specified quantities.

[00119] Pharmaceutical compositions containing the Petition 870250083412, dated 09 / 16 / 2025, page 53 / 105 36 / 79 The active ingredient may be in a form suitable for oral use, for example, as tablets, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups or elixirs. Compositions intended for oral use may be prepared according to any method known in the art for the manufacture of pharmaceutical compositions, and such compositions may contain one or more agents selected from the group consisting of sweetening agents, flavoring agents, coloring agents, and preservatives in order to provide pharmaceutically elegant and palatable preparations. Tablets contain the active ingredient in a mixture with pharmaceutically acceptable non-toxic excipients which are suitable for the manufacture of tablets.These excipients may be, for example, inert diluents such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example, corn starch or alginic acid; binding agents, for example, starch, gelatin or acacia; and lubricating agents, for example, magnesium stearate, stearic acid or talc. The tablets may be uncoated or they may be coated by techniques known to retard disintegration and absorption in the gastrointestinal tract. Petition 870250083412, dated 09 / 16 / 2025, page 54 / 105 37 / 79 thus provide sustained action over a longer period. For example, a time-retardant material such as glyceryl monostearate or glyceryl distearate may be employed. They may also be coated by the techniques described in U.S. Patents 4,256,108; 4,166,452; and 4,265,874 to form osmotic therapeutic tablets for controlled release. Formulations for oral use may also be presented as hard gelatin capsules in which the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules in which the active ingredient is mixed with water or an oily medium, for example, peanut oil, liquid paraffin or olive oil.

[00120] Pharmaceutical compositions may be in the form of a sterile aqueous or oily injectable suspension. This suspension may be formulated according to known techniques using those suitable dispersing or wetting agents and suspending agents mentioned above. The sterile injectable preparation may also be a sterile injectable solution or suspension in a parenterally acceptable non-toxic diluent or solvent, for example, a solution in 1,3-butanediol. Acceptable vehicles and solvents that may be used include water, Ringer's solution, and isotonic chloride solution. Petition 870250083412, dated 09 / 16 / 2025, page 55 / 105 38 / 79 sodium. Furthermore, sterile fixed oils are conventionally used as a solvent or suspension medium. For this purpose, any tasteless fixed oil can be used, including synthetic mono- or diglycerides. Additionally, fatty acids such as oleic acid are useful in the preparation of injectables.

[00121] The compounds of the present invention can also be administered in the form of suppositories for rectal administration of the drug. These compositions can be prepared by mixing the drug with a suitable non-irritating excipient that is solid at normal temperatures but liquid at rectal temperature and therefore melts in the rectum to release the drug. Such materials are cocoa butter and polyethylene glycols.

[00122] For topical use, creams, ointments, gels, solutions or suspensions, etc., containing the compounds of the present invention are employed.

[00123] In the treatment or prevention of HSP90-related diseases, an appropriate dosage level will generally be about 0.01 to 250 mg per kg of the patient's body weight per day (mg / kg per day), which may be administered in single or multiple doses. Preferably, the dosage level will be about 0.1 to about 100 mg / kg per day, such as 0.1 to about 50 mg / kg per day. For oral administration, the wording, in a manner Petition 870250083412, dated 09 / 16 / 2025, p. 56 / 105 39 / 79 preferred, are provided in the form of tablets containing 1.0 to 1000 mg of the active ingredient for symptomatic dosage adjustment for the patient being treated. The compounds may be administered as a single daily dose, divided into one or more daily doses, for example, in a regimen of 1 to 4 times a day. It will be understood, however, that the specific dose level and dosing frequency for any particular patient may vary and will depend on a variety of factors including the activity of the specific compound employed, the metabolic stability and duration of action of that compound, age, body weight, general health, sex, diet, mode and time of administration, excretion rate, drug combination, severity of the particular condition and the host in therapy. Examples

[00124] The present invention is further illustrated by the following examples. Abbreviations

[00125] The following abbreviations are used: ACN: acetonitrile, AcOH: acetic acid, Ar: argon, CyHex: cyclohexane, DCM: dichloromethane, Petition 870250083412, dated 09 / 16 / 2025, p. 57 / 105 40 / 79 DMF: N,N-dimethylformamide, eq: equivalent, EtOAc or AcOEt: ethyl acetate, EtOH: ethanol, g: grams, h: hour(s), L: liters, MeOH: methanol, mg: milligrams, mL: milliliters, mmol: millimoles, mol: moles, M: mol / L, MS: mass spectrometry, MTBE: methyl tert-butyl ether, PMB: para-methoxybenzyl, RT or rt: room temperature, TEA: triethylamine, TFA: trifluoroacetic acid, THF: tetrahydrofuran, TLC: thin-layer chromatography, μL: microliters. Chemical Examples General Procedures

[00126] The compounds of the invention may be Petition 870250083412, dated 09 / 16 / 2025, p. 58 / 105 41 / 79 synthesized using the general paths described in Scheme 1 below. Scheme 1: General scheme for the synthesis of the compounds of the invention. Cul, neocuproin tBuONa DMF, 120°C, 20h Synthesis of the Compounds of the Invention Compound 2- ( (6((cyclopropylmethyl)(methyl)amino)benzo[d][1,3]dioxol-5yl)thio)-1-(2-(neopentylamino)ethyl)-IH-imidazo[4,5 c]pyridin-4-amine Synthesis of the Intermediate (II-l)

[00127] Step 1: N2,N2-bis[(4-methoxyphenyl)methyl]-3nitro-pyridine-2,4-diamine PMB2-NH, EtgN EtOH, 90 °C, 8h Petition 870250083412, dated 09 / 16 / 2025, p. 59 / 105 42 / 79

[00128] To a stirred solution of l-(4-methoxyphenyl)N-[(4-methoxyphenyl)methyl]methanamine (4.45 g, 17.3 mmol, 1.2 eg.) and triethylamine (3.0 mL, 21.6 mmol, 1.5 eg.) in EtOH (36 mL, [C] = 0.4 M) was added 2-chloro-3-nitropyridin-4-amine (2.50 g, 14.4 mmol) at RT and the resulting mixture was stirred at 90 °C for 8 h. After cooling to RT, the mixture was concentrated under reduced pressure. The residue was partitioned between saturated aqueous NH4Cl and EtOAc. The layers were separated and the aqueous phase was extracted with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4), filtered, and concentrated to give the title compound, 5.60 g (92% yield) as an orange oil. The crude product was used directly in the next step without further purification. MS (ESI+) : [M+H] + = 395 .

[00129] Step 2: N2,N2-bis[(4methoxyphenyl)methyl]pyridine-2,3,4-triamine 10% Pd / C, H2 EtOH, RT, 20h

[00130] To a stirred solution of N2,N2-bis[(4-methoxyphenyl)methyl]-3-nitropyridine-2,4-diamine (5.06 g, 12.8 mmol) in EtOH (60 mL, [C] = 0.2 M) palladium on carbon (10% Pd / C, 546 mg, 2.57 mmol) was added Petition 870250083412, dated 09 / 16 / 2025, pp. 60 / 105 43 / 79 RT under Ar and the resulting mixture was stirred under an H2 atmosphere at RT for 4 h. The mixture was filtered over a Celite layer and the filtrate was concentrated. The residue was purified by flash chromatography on silica gel (DCM / 7N in NH3 in MeOH, 90 / 10) to give the title compound, 3.53 g (75% yield) as an orange oil. MS (ESI+) : [M+H]+= 365.

[00131] Step 3: 4-[bis[(4-methoxyphenyl)methyl]amino]IH-imidazo[4,5-c]pyridine-2-thiol (Intermediate II-l) s

[00132] To a stirred solution of N2,N2-bis[(4-methoxyphenyl)methyl]pyridine-2,3,4-triamine (3.53 g, 9.69 mmol) in T&H (48 mL, [C] = 0.2 M) was added 1,1-thiocarbonyl diimidazole (2.59 g, 14.5 mmol, 1.5 e.g.) at RT and the resulting mixture was stirred at RT for 4 h. The mixture was concentrated under reduced pressure and the residue was purified by flash chromatography on silica gel (CyHex. / EtOAc, 9 / 1 to 2 / 1) to give Intermediate II-l, 2.80 g (71% yield) as a pink foam. MS (ESI+): [M+H]+ = 407. Synthesis of the Intermediate (III-l) Step 1: N-(cyclopropylmethyl)-6-iodo-1,3-benzodioxol Petition 870250083412, dated 09 / 16 / 2025, p. 61 / 105 44 / 79 5-amine

[00133] To a stirred solution of 6-iodo-1,3benzodioxol-5-amine (2.0 g, 7.07 mmol) in DCM (29 mL, [C] = 0.25 M) was added cyclopropanecarboxaldehyde (580 pL, 7.785 mmol, 1.1 eg.) followed by AcOH (1.2 mL, 21.2 mmol, 3 eg.) at RT and the resulting mixture was stirred at RT for 1 h. Sodium triacetoxyborohydride (4.5 g, 21.2 mmol, 3 eg.) was added at 0°C and the resulting mixture was stirred at RT for 1 h. Saturated aqueous NaHCO3 was added under vigorous stirring. The phases were separated and the aqueous phase was extracted with DCM (2x). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (CyHex. / EtOAc (1 / 0 to 4 / 1)) to provide the title compound, 1.46 g (52% yield) as a yellow oil. MS (ESI+): [M+H]+ = 318. Step 2: N-(cyclopropylmethyl)-6-iodo-N-methyl-1,3-benzodioxol-5-amine (Intermediate III-1) NaH, Mel DMF, RT, 48h Petition 870250083412, dated 09 / 16 / 2025, p. 62 / 105 45 / 79

[00134] To a stirred solution of N(cyclopropylmethyl)-6-iodo-1,3-benzodioxol-5-amine (1.46 g, 3.68 mmol) in dry DMF (10 mL, [C] = 0.4 M), NaH (60% in mineral oil, 220 mg, 5.52 mmol, 1.5 eq.) was added at 0 °C and the resulting mixture was stirred at RT for 30 min. Iodomethane (0.57 mL, 9.20 mmol, 2.5 eq.) was added and the resulting mixture was stirred at RT for 26 h. The solution was partitioned between EtOAc and water and the layers were separated. The organic phase was washed with water (2x), brine, dried (Na2SO4), filtered and concentrated. The crude product (2.5 g) was purified by flash chromatography on silica gel (CyHex. / EtOAc (1 / 0 to 97 / 3)) to give Intermediate III-1, 700 mg (57% yield) as a yellow oil. MS (ESI+) : [M+H]+= 332. Synthesis of Compound 001 Step 1: 2-[[6-[cyclopropylmethyl(methyl)amino]-1,3benzodioxol-5-yl]sulfanyl]-Ν,Ν-bis[(4-methoxyphenyl)methyl]IH-imidazo[4,5-c]pyridin-4-amine (Intermediate IV-1)

[00135] A microwaveable jar was loaded with the Intermediate II-l 4-[bis[(4-methoxyphenyl)methyl]amino]-1H Petition 870250083412, dated 09 / 16 / 2025, pp. 63 / 105 46 / 79 imidazo[4,5-c]pyridine-2-thiol (200 mg, 0.492 mmol), Intermediate III-1 N-(cyclopropylmethyl)-6-iodo-N-methyl-1,3-benzodioxol-5-amine (179 mg, 0.541 mmol, 1.1 eq.), sodium tectobutylate (118 mg, 1.23 mmol, 2.5 eq.), neocuproin (20 mg, 0.0984 mmol, 0.2 eq.) and copper(I) iodide (19 mg, 0.0984 mmol, 0.2 eq.). The flask was closed and purged with argon for 10 min. Degassed DMF (2.5 mL, [C] = 0.2 M) was added and the resulting mixture was stirred at 120 °C for 17 h. After cooling to RT, the mixture was diluted with EtOAc and quenched with saturated aqueous NH4Cl. The layers were separated and the aqueous phase was extracted with EtOAc (2x). The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated. The residue (432 mg) was purified by flash chromatography on silica gel (CyHex. / EtOAc, 4 / 1 to 3 / 1) to give the title compound of Intermediate IV-1, 204 mg (68% yield) as a white solid. MS (ESI+): [M+H]+ = 610. Step 2 (A and B): 2-[[6-[cyclopropylmethyl(methyl)amino]1,3-benzodioxol-5-yl]sulfanyl]-1-[2-(2,2dimethylpropylamino)ethyl]-N,N-bis[(4methoxyphenyl)methyl]imidazo[4,5-c]pyridin-4-amine Petition 870250083412, dated 09 / 16 / 2025, pp. 64 / 105 47 / 79 DMF, RT, 7 days Stage B

[00136] Step A: To a stirred solution of Intermediate IV-1 2-[[6-[cyclopropylmethyl(methyl)amino]1,3-benzodioxol-5-yl]sulfanyl]-N,N-bis[(4-methoxyphenyl)methyl]-IH-imidazo[4,5-c]pyridin-4-amine (200 mg, 0.328 mmol) in dry DMF (1.8 mL, 0.18 M) was added cesium carbonate (267 mg, 0.82 mmol, 2.5 eq.) followed by 1,2-dibromoethane (0.14 mL, 164 mmol, 5.0 eq.) at RT and the resulting mixture was stirred at RT for 1.5 h. The mixture was poured into water and extracted with EtOAc (2x). The combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated to give the intermediate, 293 mg, as a light green oil.

[00137] Step B: The intermediate was dissolved in DMF (1.64 mL, 0.17 M) and neopentylamine (0.50 mL, 6.43 Petition 870250083412, dated 09 / 16 / 2025, pp. 65 / 105 48 / 79 mmols, 13 eq.) RT was added and the resulting mixture was stirred at RT for 7 days. The mixture was concentrated and purified by flash chromatography on silica gel (CyHex. / EtOAc, 3 / 1 to 1 / 1) to give the title compound, 150 mg (63% yield) as a colorless oil. MS (ESI+) : [M+H]+ = 723. Step 3: 2-((6((cyclopropylmethyl)(methyl)amino)benzo[d][1,3]dioxol-5yl)thio)-1-(2-(neopentylamino)ethyl)-IH-imidazo[4,5c]pyridin-4-amine (Compound 001)

[00138] A solution of 2—[ [6 — [cyclopropylmethyl(methyl)amino]-1,3-benzodioxol-5yl]sulfanyl]-1-[2-(2,2-dimethylpropylamino)ethyl]-N,N-bis[(4-methoxyphenyl)methyl]imidazo[4,5-c]pyridin-4-amine (150 mg, 0.197 mmol) in trifluoroacetic acid (1.5 mL) was stirred at RT for 3 days. The reaction mixture was concentrated in vacuo and the residue was diluted in H2O. Saturated aqueous NaHCO3 was added and the aqueous layer was extracted with DCM (3x). The combined organic layers were dried (Na2SO4), filtered and concentrated. The crude mixture (61 mg) was Petition 870250083412, dated 09 / 16 / 2025, pp. 66 / 105 49 / 79 purified by TLC preparation on silica gel (DCM / MeOH, 95 / 5) to give Compound 001, 20 mg (20% yield) as a green oil. MS (ESI+) : [M+H]+= 483.

[00139] The product was dissolved in MeOH (1 mL) and 0.5 N HCl in MeOH (2 eq.) was added. After 5 min, the product was concentrated and dried under reduced pressure at 40 °C to give the corresponding bishydrochloride salt. Compound 002:8 — ( (6 — ((cyclopropylmethyl)(methyl)amino)benzo[d][1,3]dioxol-5yl)thio)-9-(2-(neopentylamino)ethyl)-9H-purin-6~amine Synthesis of Compound 002 Step 1: 8-[[6-[cyclopropylmethyl(methyl)amino]-1,3benzodioxol-5-yl]sulfanyl]-9H-purin-6-amine (Intermediate IV-2)

[00140] A microwaveable flask was loaded with 6-amino-9H-purine-8-thiol (Intermediate II-2) (115 mg, 0.688 mmol), Intermediate III-1 N-(cyclopropylmethyl)-6-iodo-N-methyl-1,3-benzodioxol-5-amine (239 mg, 0.722 mmol, 1.05 eq.), sodium tecto-butylate (165 mg, 1.72 mmol, 2.5 Petition 870250083412, dated 09 / 16 / 2025, p. 67 / 105 50 / 79 eq.), neocuprin (29 mg, 0.138 mmol, 0.2 eq.) and copper(I) iodide (26 mg, 0.138 mmol, 0.2 eq.). The flask was closed and purged with argon for 10 min. Degassed DMF (2.7 mL, [C] = 0.2 M) was added and the resulting mixture was stirred at 120 °C for 20 h. After cooling to RT, the mixture was diluted with EtOAc and quenched with saturated aqueous NH4Cl. The layers were separated and the aqueous phase was extracted with EtOAc (2x). The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel (DCM / MeOH, 96 / 4) to give the title compound, Intermediate IV-2, mg (15% yield) as an orange oil. MS (ESI+): [M+H]+ = 371. Step 2 (A and B): 8-((6( (cyclopropylmethyl) (methyl)amino)benzo[d] [1,3]dioxol-5yl)thio)-9-(2-(neopentylamino)ethyl)-9H-purin-6-amine (Compound 002) Br Br Gs2CO3 <dmf, rt, 2hStage A Stage B DMF, RT, 7 days

[00141] Stage A: A solution to Intermediate IV-2 8-[[6-[cyclopropylmethyl(methyl)amino]-1,3-benzodioxol-5yl]sulfanyl]-9H-purin-6-amine (37 mg, 0.10 mmol) diluted in Petition 870250083412, dated 09 / 16 / 2025, pp. 68 / 105 51 / 79 Dry DMF (1 mL, [C] = 0.1 M) was added to cesium carbonate (81 mg, 0.25 mmol, 2.5 eq.) followed by 1,2-dibromoethane (43 mL, 0.50 mmol, 5.0 eq.) at RT and the resulting mixture was stirred at RT for 2 h. The mixture was poured into water and extracted with EtOAc (2x). The combined organic extracts were washed with brine, dried (NazSO₄), filtered and concentrated to give the intermediate, 46 mg as an orange oil.

[00142] Stage B: The intermediary was dissolved in DMF (1 mL, [C] = 0.1 M) and neopentylamine (0.18 mL, 1.5 mmol, 15 eq.) were added at RT and the resulting mixture was stirred at RT for 20 h. The mixture was concentrated and purified by flash chromatography on silica gel (DCM / MeOH, 95 / 5) to give Compound 002, 20 mg (41% yield) as a light yellow solid. MS (ESI+): [M+H]+ = 484.

[00143] The product was dissolved in MeOH (1 mL) and 0.5 N HCl in MeOH (2 eq.) was added. After 5 min, the product was concentrated and dried under reduced pressure at 40 °C to give the corresponding bis-hydrochloride salts. Compound 003:8-((6(allyl(methyl)amino)benzo[d][1,3]dioxol-5-yl)thio)-9-(2(neopentylamino)ethyl)-9H-purin-6-amine Synthesis of the Intermediate (III-2) Step 1: N-allyl-6-iodo-1,3-benzodioxol-5-amine Petition 870250083412, dated 09 / 16 / 2025, pp. 69 / 105 52 / 79 Br K2CO3, DMF, RT, 20h

[00144] To a solution of 6-iodo-1,3-benzodioxol-5amine (900 mg, 3.42 mmol) in DMF (6.8 mL, [C] = 0.5 M) was added potassium carbonate (709 mg, 5.13 mmol, 1.5 eq.) followed by allyl bromide (0.31 mL, 3.59 mmol, 1.05 eq.) at RT and the resulting mixture was stirred at RT for 20 h. Most of the DMF was removed under reduced pressure and the residue was dissolved in EtOAc (50 mL). The organic layer was washed with water, brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (CyHex. / EtOAc, 1 / 0 to 4 / 1) to give the title compound, 566 mg (52% yield) as a yellow oil. MS (ESI+): [M+H]+= 304. Step 2: N-allyl-6-iodo-N-methyl-1,3-benzodioxol-5-amine (Intermediate III-2) NaH, Mel DMF, RT, 48h

[00145] To a stirred solution of N-allyl-6-iodo-1,3-benzodioxol-5-amine (420 mg, 1.38 mmol) in dry DMF (3.9 mL, [C] = 0.4 M) NaH (60% in mineral oil, mg, 1.66 mmol, 1.2 eq.) was added at 0 °C and the resulting mixture Petition 870250083412, dated 09 / 16 / 2025, pp. 70-105 53 / 79 was stirred at RT for 30 min. Iodomethane (0.10 mL, 1.66 mmol, 1.2 eq.) was added and the resulting mixture was stirred at RT for 20 h. The solution was partitioned between EtOAc and water and the layers were separated. The organic phase was washed with water (2x), brine, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel (CyHex. / EtOAc, 1 / 0 to 97 / 3) to give Intermediate III-2, 383 mg (64% yield) as a yellow oil. MS (ESI+): [M+H]+ = 318. Synthesis of Compound 003 Step 1: 8-[[6-[alii(methyl)amino]-1,3-benzodioxol-5yl]sulfanyl]-9H-purin-6-amine (Intermediate IV-3) Cul, neocuproina.tBuONa DMF, 120°C, 8pm

[00146] A microwaveable flask was loaded with 6-amino-9H-purine-8-thiol (Intermediate II-2) (184 mg, 1.10 mmol), Intermediate III-2 N-allyl-6-iodo-N-methyl-1, 3-benzodioxol-5-amine (384 mg, 1.21 mmol, 1.1 eq.), sodium thiobutylate (264 mg, 2.75 mmol, 2.5 eq.), neocuprin (46 mg, 0.22 mmol, 0.2 eq.), and copper(I) iodide (42 mg, 0.22 mmol, 0.2 eq.). The flask was closed and purged with Petition 870250083412, dated 09 / 16 / 2025, pp. 71 / 105 54 / 79 argon for 10 min. Degassed DMF (4.7 mL, [C] = 0.25 M) was added and the resulting mixture was stirred at 120 °C for 20 h. After cooling to RT, the mixture was diluted with EtOAc and quenched with saturated aqueous NH4Cl. The layers were separated and the aqueous phase was extracted with EtOAc (2x). The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel (CyHex. / EtOAc, 4 / 1 to 3 / 1) to give Intermediate IV3, 139 mg (32% yield) as an orange solid. MS (ESI+): [M+H]+= 357. Step 2 (A and B): 8-((6(allyl(methyl)amino)benzo[d][1,3]dioxol-5-yl)thio)-9-(2(neopentylamino)ethyl)-9H-purin-6-amine (Compound 003) Stage A: Cs2CO3, DMF, RT, 1.5h Stage B: NH2 DMF, RT, 8 PM

[00147] Stage A: A solution to Intermediate IV-3 8-[[6-[allyl(methyl)amino]-1,3-benzodioxol-5-yl]sulfanyl]-9H purin-6-amine (138 mg, 0.35 mmol) diluted in dry DMF (3.5 Petition 870250083412, dated 09 / 16 / 2025, pp. 72-105 Cesium carbonate (170 mg, 0.52 mmol, 1.5 eq.) was added followed by 1,2-dibromoethane (0.15 mL, 1.74 mmol, 5.0 eq.) at RT and the resulting mixture was stirred at RT for 1.5 h. The mixture was concentrated and purified by preparative TLC on silica gel (CyHex. / EtOAc, 2 / 3) to give the title compound, 55 mg (33% yield) as a white solid. MS (ESI+): [M+H]+ = 464 / 466.

[00148] Step B: To a solution of 8-[[6[allyl(methyl)amino]-1,3-benzodioxol-5-yl]sulfanyl]-9-(2-bromoethyl)purin-6-amine (55 mg, 0.114 mmol) dissolved in DMF (1.1 mL, [C] = 0.1 M) was added neopentylamine (0.54 mL, 4.56 mmol, 40 eq.) at RT and the resulting mixture was stirred at RT for 20 h. The mixture was concentrated and purified by preparative TLC on silica gel (DCM / MeOH, 95 / 5) to give Compound 003, 47 mg (86% yield) as a white solid. MS (ESI+): [M+H]+= 470.

[00149] The product was dissolved in MeOH (1 mL) and 0.5 N HCl in MeOH (2 eq.) was added. After 5 min, the product was concentrated and dried under reduced pressure at 40 °C to give the corresponding bis-hydrochloride salts. Compound 004:8 - ((6- (allyl (methyl)amino) -2,2difluorobenzo[d][1A3]dioxol-5-yl)thiO)-9-(2(neopentylamino)ethyl)-9H-purin-6-amine Synthesis of the Intermediate (III-3) Step 1: N-allyl-2,2-difluoro-6-iodo-1,3-benzodioxol-5 Petition 870250083412, dated 09 / 16 / 2025, page 73 / 105 56 / 79 amine K2CO3, DMF, RT, 20h

[00150] To a solution of 2,2-difluoro-6-iodo-1,3benzodioxol-5-amine (2.0 g, 6.69 mmol) in DMF (8.4 mL, [C] = 0.8 M) was added potassium carbonate (1.85 g, 13.4 mmol, 2 eq.) followed by allyl bromide (0.87 mL, 10.0 mmol, 1.5 eq.) at RT and the resulting mixture was stirred at RT for 20 h. Most of the DMF was removed under reduced pressure and the residue was dissolved in EtOAc (50 mL). The organic layer was washed with water, brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (CyHex. / EtOAc, 1 / 0 to 9 / 1) to give the title compound, 1.25 g (55% yield) as a colorless oil. MS (ESI+): [M+H]+= 340. Step 2: N-allyl-2,2-difluoro-6-iodo-N-methyl-1,3-benzodioxol-5-amine (Intermediate III-3) NaH, Mel DMF, RT, 48h

[00151] To a stirred solution of N-allyl-2,2-difluor 6-iodo-1,3-benzodioxol-5-amine (500 mg, 1.40 mmol) in DMF Petition 870250083412, dated 09 / 16 / 2025, pp. 74 / 105 57 / 79 dry (3.1 mL, [C] = 0.45 M) NaH (60% in mineral oil, 67 mg, 1.66 mmol, 1.2 eq.) was added at 0 °C and the resulting mixture was stirred at RT for 30 min. Iodomethane (95 pL, 1.54 mmol, 1.1 eq.) was added and the resulting mixture was stirred at RT for 4 h. The solution was partitioned between EtOAc and water and the layers were separated. The organic phase was washed with water (2x), brine, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel (CyHex. / EtOAc, 1 / 0 to 9 / 1) to give Intermediate III-3, 430 mg (87% yield) as a colorless oil. MS (ESI+) : [M+H] + = 354 . Synthesis of Compound 004 Step 1: 8-[[6-[alii(methyl)amino]-2,2-difluoro-1,3benzodioxol-5-I1]sulfanyl]-9H-purin-6-amine (Intermediate IV-4) Cul, neocuproina.tBuONa DMF, 120°C, 8 PM

[00152] A microwaveable jar was loaded with 6-amino-9H-purine-8-thiol (Intermediate II-2) (90 mg, 0.54 mmol), N-allyl-6-iodo-N-methyl-1,3-benzodioxol-5-amine Petition 870250083412, dated 09 / 16 / 2025, pp. 75 / 105 58 / 79 (190 mg, 0.54 mmol, 1 eq.), sodium tectobutylate (129 mg, 1.34 mmol, 2.5 eq.), neocuprin (22 mg, 0.11 mmol, 0.2 eq.) and copper(I) iodide (20 mg, 0.11 mmol, 0.2 eq.). The flask was closed and purged with argon for 10 min. Degassed DMF (2.7 mL, [C] = 0.2 M) was added and the resulting mixture was stirred at 120 °C for 20 h. After cooling to RT, the mixture was diluted with EtOAc and quenched with saturated aqueous NH4Cl. The layers were separated and the aqueous phase was extracted with EtOAc (2x). The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated. The residue was purified by flash chromatography on silica gel (DCM / MeOH, 95 / 5) to give the title compound, 49 mg (23% yield) as an orange solid. MS (ESI+): [M+H]+ = 393. Step 2 (A and B): 8-((6-(allyl(methyl)amino)-2,2difluorobenzo[d][1,3]dioxol-5-yl)thio)-9-(2(neopentylamino)ethyl)-9H-purin-6-amine (Compound 004) Stage A: CS2CO3, DMF, RT, 20h Br Petition 870250083412, dated 09 / 16 / 2025, pp. 76 / 105 59 / 79 Br nh2 DMF, RT, 8 PM N NHo N H ,----IN ,----N Step B: =7= / \

[00153] Step A: To a solution of 8-[[6[allyl(methyl)amino]-2,2-difluoro-1,3-benzodioxol-5yl]sulfanyl]-9H-purin-6-amine (49 mg, 0.12 mmol) diluted in dry DMF (1.2 mL, [C] = 0.1 M) was added cesium carbonate (102 mg, 0.31 mmol, 2.5 eq.) followed by 1,2-dibromoethane (54 μL, 0.62 mmol, 5.0 eq.) at RT and the resulting mixture was stirred at RT for 20 h. The mixture was concentrated and purified by preparative TLC on silica gel (CyHex. / EtOAc, 2 / 3) to give the title compound, 22 mg (35% yield) as a white solid. MS (ESI+): [M+H]+= 499 / 501.

[00154] Step B: To a solution of 8-[[6[allyl(methyl)amino]-2,2-difluoro-1,3-benzodioxol-5yl]sulfanyl]-9-(2-bromoethyl)purin-6-amine (22 mg, 44 μmol) dissolved in DMF (0.9 mL, [C] = 0.05 M) was added neopentylamine (104 μL, 0.88 mmol, 20 eq.) at RT and the resulting mixture was stirred at RT for 20 h. The mixture was concentrated and purified by preparative TLC on silica gel (DCM / MeOH, 95 / 5) to give Compound 004, 19 mg (84% yield) as a white solid. MS (ESI+): [M+H]+= 506.

[00155] The product was dissolved in MeOH (1 mL) and 0.5 N HCl in MeOH (2 eq.) was added. After 5 min, the Petition 870250083412, dated 09 / 16 / 2025, pp. 77 / 105 60 / 79 product was concentrated and dried under reduced pressure at 40 °C to give the corresponding bis-chloride salts. Compound 005:2-((6-((2,2difluoroethyl)(methyl)amino)benzo[d][1,3]dioxol-5-yl)thio)-1(2-(neopentylamino)ethyl)-1H-imidazo[4,5-c]pyridin-4-amine Synthesis of the Intermediate (III-4)

[00156] Step 1: 2,2-difluoro-N-(6iodobenzo[d][1,3]dioxol-5-yl)acetamide F

[00157] To a solution of the compound 6iodobenzo[d][1,3]dioxol-5-amine (2.00 g, 7.60 mmol, 1.00 eq.) in THF (20.0 mL) was added TEA (2.31 g, 22.8 mmol, 3.17 mL, 3.00 eq.) at 0°C and stirred at 25°C for 0.5 h. Then, the compound 2,2-difluoroacetic anhydride (1.99 g, 11.4 mmol, 1.50 eq.) was added to the mixture at 0°C and stirred at 25°C for 1 h. The reaction mixture was poured into ice water (50.0 mL) at 10°C. The aqueous layer was extracted with EtOAc (20.0 mL x 3). The combined organic layer was washed with brine (20.0 mL x 2), dried over Na2SO4, filtered, and concentrated under reduced pressure to give a crude product. The crude product was purified by column chromatography (SiO2, petroleum ether / acetate of Petition 870250083412, dated 09 / 16 / 2025, pp. 78 / 105 61 / 79 ethyl = 100 / 1 to 0 / 1, Rf = 0.70) to give the title compound (2.10 g, 6.15 mmol, 80.9% yield, 99.9% purity) as a white solid. MS: [M+H]+ = 340.0 Step 2: 2,2-difluoro-N-(6-iodobenzo[d][1,3]dioxol-5yl)-N-methylacetamide F

[00158] To a solution of 2,2-difluoro-N-(6iodobenzo[d][1,3]dioxol-5-yl)acetamide (2.05 g, 6.01 mmol, 1.00 eq.) in DMF (20.0 mL) was added NaH (289 mg, 7.23 mmol, 60.0% purity, 1.20 eq.) at 0 °C and stirred at 25 °C for 0.5 h. Honey (1.02 g, 7.21 mmol, 449 pL, 1.20 eq.) was added dropwise to the mixture at 0 °C and stirred at 25 °C for 1 h. The reaction mixture was poured into chilled saturated aqueous solution of NH4Cl (100 mL) at 0-10°C and extracted with ethyl acetate (30.0 mL x 3). The combined organic layer was washed with brine (30.0 mL x 3), dried over Na2SO4, filtered, and concentrated under reduced pressure to give a crude product. The crude product was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 100 / 1 to 1 / 1, Rf = 0.40) to give the title compound (1.1 g, 3.09 mmol, 51.5% yield, 99.9% purity) as a white solid. MS: [M+H]+ = 356.0 Petition 870250083412, dated 09 / 16 / 2025, pp. 79 / 105 62 / 79 Step 3: N-(2,2-difluoroethyl)-6-iodo-N-methylbenzo[d][1,3]dioxol-5-amine (Intermediate III-4)

[00159] To a solution of 2,2-difluoro-N-(6iodobenzo[d][1,3]dioxol-5-yl)-N-methylacetamide (1.10 g, 3.10 mmol, 1.00 eq.) in THF (3.00 mL) was added BH3. THF (1.00 M, 9.66 mL, 3.12 eq.) was heated to 25 °C. The mixture was stirred at 70 °C for 2 h. The reaction mixture was poured into saturated aqueous NH4Cl solution (30.0 mL) at 0 ~ 10 °C and extracted with ethyl acetate (15.0 mL x 3). The combined organic layer was washed with brine (15.0 mL x 2), dried over Na2SO4, filtered, and concentrated under reduced pressure to give a crude product. The crude product was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 100 / 1 to 1 / 1, Rf = 0.60) to give Intermediate III-4 (1.02 g, 2.86 mmol, 92.3% yield, 95.7% purity) as a yellow oil. MS: [M+H]+ = 352.1 Synthesis of Compound 005 Step 1: 2-[(6-((2,2-difluoroethyl)(methyl)amino)-1,3benzodioxol-5-yl)sulfanyl]-N,N-bis[(4-methoxyphenyl)methyl]1H-imidazo[4,5-c]pyridin-4-amine (Intermediate IV-5) Petition 870250083412, dated 09 / 16 / 2025, pp. 80 / 105 63 / 79 PMB SH Cs2CO3, XantPhos Pd G3 dioxane, 25-100°C, 2h

[00160] A solution of Intermediate II-1 (1.20 g, 2.95 mmol, 1.00 eg.) and Intermediate III-4 (1.01 g, 2.95 mmol, 1.00 eg.) in dioxane (10 mL) was added CS2CO3 (2.40 g, 7.38 mmol, 2.50 eg) and XantPhos Pd G3 (560 mg, 590 pmol, 0.200 eg) were mixed at 25 °C under air. The mixture was then stirred at 100 °C for 2 h under air. The reaction mixture was cooled to 25 °C and poured into ice water (50.0 mL) at 10 °C. The aqueous layer was extracted with EtOAc (30.0 mL x 3). The combined organic layer was washed with brine (30.0 mL x 3), dried over Na2SO4, filtered, and concentrated under reduced pressure to give a residue. The residue was purified by preparative HPLC (column: UniSil 10-120 C18 70x250 mm; mobile phase: [water (NH4HCO3) ACN]; gradient: 50%-80% B over 20 min) to give a crude product. The crude product was then purified by preparative TLC (SiO2, Petroleum ether: Ethyl acetate = 1:1, Rf = 0.60) to give the Intermediate IV-5 of the title (180 mg, 283 pmols, 9.58% yield, 97.4% purity) as a yellow oil. MS: [M+H]+ = 620.4 Petition 870250083412, dated 09 / 16 / 2025, pp. 81 / 105 64 / 79 Step 2 (A, B and C): 2-((6-((2,2difluoroethyl)(methyl)amino) benzo[d][1,3]dioxol-5-yl)thio)-1(2- ​​(neopentylamino)ethyl)-ΙΗ-Ν,Ν-bis[(4methoxyphenyl)methyl]imidazo[4,5-c]pyridin-4-amine Stage A: rNHBoc Br-7b 2.00 eq b, 2.50 eq Cs2CO3, DMF (10 V), 25 ·- 50 °C, 4 h Gross Product Stage B: M HCl / MeOH (10 V). °C, 1 h Gross Product PMB i

[00161] Step Ai A solution of Intermediate IV-5 (180 mg, 290 pmols, 1.00 eg.) in DMF (2.00 mL) was added to CS2CO3 (237 mg, 727 pmols, 2.50 eg.) and compound b (131 mg, 584 pmols, 2.01 eg.) at 25 °C. The mixture was stirred at 50 °C for 4 h. The reaction mixture was cooled to 25 °C and poured into ice water (30 mL). The aqueous layer was extracted with EtOAc (15.0 mL x 3). As Petition 870250083412, dated 09 / 16 / 2025, pp. 82 / 105 65 / 79 combined organic layers were washed with brine (15.0 mL x 2), dried over Na2SO4, filtered, and concentrated under reduced pressure to give the resulting compound (300 mg, crude) as a yellow oil. MS: [M+H]+ = 763.5

[00162] Step B: The compound resulting from step A (220 mg, 288 pmols, 1.00 eq.) in HCl / MeOH (2 M, 2.00 mL, 13.8 eq.) was stirred at 25°C for 1 h. The reaction mixture was slowly poured onto ice with 20% NaHCO3 (30.0 mL) at 10°C. The aqueous layer was extracted with EtOAc (15.0 mL x 3). The combined organic layers were washed with brine (15.0 mL x 2), dried over Na2SO4, filtered, and concentrated under reduced pressure to give the corresponding unprotected compound (190 mg, crude) as a yellow oil. MS: [M+H]+= 663.4

[00163] Step C: To a solution of the compound from step B (190 mg, 287 pmols, 1.00 eq.) and compound c (38.0 mg, 441 pmols, 48.8 pL, 1.54 eq.) in DCM (2.00 mL) was added NaBH(OAc)3 (152 mg, 717 pmols, 2.50 eq.) and HOAc (2.00 mg, 33.3 pmols, 1.91 pL, 0.100 eq.) at 0 °C. The mixture was stirred at 25 °C for 5 h. The reaction mixture was poured into ice-cold water (30.0 mL), extracted with EtOAc (15.0 mL x 3). The combined organic layer was washed with brine (15.0 mL x 2), dried over Na2SO4, filtered, and concentrated under reduced pressure to give a yellow oil (197 mg, crude). MS: [M+H]+= 733.5 Petition 870250083412, dated 09 / 16 / 2025, pp. 83 / 105 66 / 79 Step 3: 2-((6-((2,2difluoroethyl)(methyl)amino)benzo[d][1,3]dioxol-5-yl)thio)-1(2-(neopentylamino)ethyl)-1H-imidazo[4,5-c]pyridin-4-amine (Compound 005)

[00164] The compound resulting from step C above (197 mg, 269 pmols, 1.00 eq.) in TFA (2.00 mL) was stirred at 50 °C for 3 h. The reaction mixture was slowly poured onto ice with 20% NaHCO3 (30.0 mL) at 10 °C, extracted with EtOAc (15.0 mL x 3). The combined organic layers were washed with brine (15.0 mL x 2), dried over Na2SO4, filtered, and concentrated under reduced pressure to give a crude product. The crude product was ground with MTBE (2.00 mL) at 25 °C for 2 h, then filtered, and the cake was washed with MTBE (1.00 mL x 2). The yellow solid was dissolved in ACN (2.00 mL), 1 M HCl (1.00 mL) was added and stirred at 25 °C for 0.5 h, then the mixture was diluted with water (30.0 mL) and lyophilized to give Compound 005 (45.0 mg, 83.7 pmols, 31.1% yield). 98.4% purity, HCl) as a light yellow solid. MS: [M+H]+= 493.2. 1H NMR (400 MHz, DMSO) δ 13.29 (s, 1H), Petition 870250083412, dated 09 / 16 / 2025, pp. 84 / 105 67 / 79 9.12 (br s, 2H), 8.60 (br s, 2H), 7.85 (J = 5.20 Hz, 1H), 7.66 (d, J = 7.20 Hz, 1H), 7.19 (s, 1H), 6.62 (s, 1H), 6.25 - 5.97 (m, 3H), 4.81 (t, J = 7.60 Hz, 2H), 3.36 - 3.26 (m, 4H), 2.83 - 2.71 (m, 2H), 2.71 (s, 3H), 1.01 (s, 9H). Composto 006:2-((6(ciclobutil(metil)amino)benzo[d][1,3]dioxol-5-il)tio)-1-(2(neopentilamino)etil)-1H-imidazo[4,5-c]piridin-4-amina Síntese do Intermediário (III-5) Etapa 1: N-ciclobutil-6-iodobenzo[d][1,3]dioxol-5amina

[00165] To a solution of 6-iodobenzo[d][1,3]dioxol5-amine (2.00 g, 7.60 mmol, 1.00 eq.) and cyclobutanone (600 mg, 8.56 mmol, 1.13 eq.) in DCM (20 mL) was added AcOH (46 mg, 766 pmol, 43.9 pL, 1.01 e-1 eq.) and NaBH(OAc)3 (4.84 g, 22.8 mmol, 3.00 eq.) at 0 °C under N2. The reaction mixture was quenched by the addition of 100 mL of ice-cold water at 0 °C and extracted with DCM (50.0 mL x 3). The combined organic layers were washed with 100 mL of brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 1 / 0 to 5 / 1, Rf = 0.8) to give the title compound. Petition 870250083412, dated 09 / 16 / 2025, pp. 85 / 105 68 / 79 (2.00 g, 5.68 mmol, 74.6% yield, 90.3% purity) as a yellow oil. MS: [M+H]+ = 317.9 Step 2: N-cyclobutyl-6-iodo-N-methylbenzo[d][1,3]dioxol-5-amine (Intermediate III-5) C-- / / CH2O, AcOH '-γ J O^N NaBH(OAc)3, DCM O^NH0-25°C, 3h '

[00166] To a solution of cyclobutyl-6iodobenzo[d][1,3]dioxol-5-amine (1.8 g, 5.68 mmol, 1.00 eq.) and formaldehyde (936 mg, 11.53 mmol, 2.03 eq.) in DCM (18.0 mL) was added AcOH (36.0 mg, 599 pmol, 34.3 pL, 1.06 e-1 eq.) and NaBH(OAc)3 (3.62 g, 17.1 mmol, 3.01 eq.) at 0 °C under N2. The mixture was stirred at 25 °C for 3 h. The reaction mixture was quenched by the addition of 100 mL of ice-cold water at 0 °C and extracted with DCM (50.0 mL x 3). The combined organic layers were washed with 100 mL of brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give Intermediate III-5 (1.80 g, 5.21 mmol, 91.7% yield, 95.8% purity) as a yellow oil that was used for the next step. MS: [M+H]+= 331.9 Synthesis of Compound 006 Step 1: 2-[(6-(cyclobutyl(methyl)amino)-1,3benzodioxol-5-yl)sulfanyl]-N,N-bis[(4-methoxyphenyl)methyl]1H-imidazo[4,5-c]pyridin-4-amine (Intermediate IV-6) Petition 870250083412, dated 09 / 16 / 2025, pp. 86 / 105 69 / 79 DMF, 100°C, 12h

[00167] To a solution of Intermediate II-1 (2.00 g, 4.58 mmol, 1.00 eg.) and Intermediate III-5 (1.52 g, 4.58 mmol, 1.00 eg.) in dioxane (20.0 mL) was added CS2CO3 (3.73 g, 11.4 mmol, 2.50 eg.) and XantPhos Pd G3 (435 mg, 458 pmol, 0.100) at 25 °C under Ar. The mixture was stirred at 100 °C for 12 h under Ar. The reaction mixture was poured into water (100 mL) and extracted with EtOAc (50.0 mL * 2). The combined organic layers were washed with brine (50.0 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to give the crude product. The crude product was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 100 / 1 to 1 / 1, Rf = 0.4) to give the Intermediate IV-6 of the titer (550 mg, 891 pmols, 19.5% yield, 98.8% purity) as a red solid. MS: [M+H]+ = 610.3 Step 2 (A, B and C) : 2-((6(cyclobutyl(methyl) amino)benzo[d] [1,3]dioxol-5-yl)thio)-1-(2(neophentylamino)ethyl)-ΙΗ-Ν,Ν-bis[(4methoxyphenyl)methyl]imidazo [4,5]-piamidine-4-amine Petition 870250083412, of 16 / 09 / 2025, p. 87 / 105 70 / 79 Step A: 2.00 eq b, 2.50 eq Cs2CO3. DMF (10 V), 50 °C, 5 h NHBoc 82.4% yield HCI / MeOH (2 M, 10 V), 25 °C, 20 68.9% yield DCM (10 V), 25 °C, 2tl 79.3% yield 0.10 eq AcOH, 3.00 eq NaBH(OAc)3

[00168] Step A A solution of Intermediate IV-6 (500 mg, 820 pmols, 1.00 eg.) and compound b (367 mg, 1.64 mmol, 2.00 eg.) in DMF (5 mL) was added to CS2CO3 (667 mg, 2.05 mmols, 2.50 eg.) at 25 °C under N2. The mixture was stirred at 50 °C for 5 h. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (50.0 mL * 2). The combined organic layers were washed with brine (50.0 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to give the crude product. The residue was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 100 / 1 to 1 / 1, Rf = 0.4) to give Petition 870250083412, dated 09 / 16 / 2025, pp. 88 / 105 71 / 79 the resulting compound (583 mg, 676 pmols, 82.4% yield, 87.3% purity) as a yellow oil. MS: [M+H]+ = 753.3.

[00169] Step B: The compound resulting from step A (550 mg, 730 pmols, 1.00 eq.) was added to HCl / MeOH (6.00 mL) (2 M) at 25 °C and stirred for 1.5 h under N2. The reaction mixture was diluted with water (40.0 mL) and extracted with DCM (30.0 mL χ2). The combined organic layers were washed with brine (40.0 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to give the corresponding unprotected compound (390 mg, 503 pmols, 68.9% yield, 84.2% purity) as a yellow oil which was used for the next step. MS: [M+H]+= 653.3

[00170] Step C: To a solution of the compound from step B (350 mg, 536 pmols, 1.00 eq.) and compound c (70.0 mg, 813 pmols, 89.9 pL, 1.52 eq.) in DCM (4.00 mL) was added NaBH(OAc)3 (341 mg, 1.61 mmol, 3.00 eq.) and AcOH (4 mg, 66.6 pmols, 3.81 pL, 1.24 e-1 eq.) at 25 °C. The mixture was stirred at 25 °C for 2 h. The reaction mixture was diluted with water (30.0 mL) and extracted with DCM (20.0 mL χ 2). The combined organic layers were washed with brine (20.0 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to give a yellow oil (330 mg, 425 pmols, 79.3% yield, 93.1% purity) (which was used for the next step. MS: [M+H]+= 723.3 Petition 870250083412, dated 09 / 16 / 2025, pp. 89 / 105 72 / 79 Step 3: 2-((6(cyclobutyl(methyl)amino)benzo[d][1,3]dioxol-5-yl)thio)-1-(2(neopentylamino)ethyl)-1H-imidazo[4,5-c]pyridin-4-amine (Compound 006) 0 0 0

[00171] The compound resulting from step C above (300 mg, 414.97 pmols, 1.00 eq.) was added to TFA (3 mL) at 25 °C and stirred for 12 h under N2. The reaction mixture was concentrated under reduced pressure to remove the TFA. The residue was adjusted to pH = 9~10 by NaOH solution and extracted with EtOAc (20.0 mL x 3). The combined organic layers were washed with brine (20.0 mL x 1), dried over Na2SO4, filtered, and concentrated under reduced pressure to give a residue. The residue was purified by preparative HPLC (column: Phenomenex luna C18 150*25mm*10µm; mobile phase: [water (HCl)-ACN]; gradient: 5%-35% B for 10 min) and then lyophilized to give Compound 006 (68.0 mg, 140 pmols, 33.7% yield). 99.4% purity) as a white solid. MS: [M+H]+ = 483.2. 1H NMR (400 MHz, MEOD) δ 7.69 (d, J = 7.60 Hz, 1H), 7.53 (br s, 1H), 7.41 (d, J = 7.20 Hz, 1H), 7.32 (s, 1H), 6.21 Petition 870250083412, dated 09 / 16 / 2025, pp. 90-105 73 / 79 (s, 2H), 4.95 — 4.89 (m, 1H), 4.85 — 4.81 (m, 2H), 4.36 — 4.20 (m, 1H), 3.62 (t, J = 7.20 Hz, 2H), 3.25 (br s, 3H), 3.06 (s, 2H), 2.61 — 2.32 (m, 2H), 2.25 — 2.09 (m, 2H), 1.86 — 1.64 (m, 2H), 1.16 (s, 9H). BIOLOGY EXAMPLES Example 1: Connection to HSP90

[00172] Purpose: The binding to HSP90 alpha and HSP90 beta of the compounds of the invention and the reference compounds Debio0932 was evaluated by fluorescent polarization.

[00173] Material and method: Fluorescence polarization was used to evaluate the binding of the compounds to alpha (N-terminal, ref 50298 BPS) and beta (N-terminal, ref 50299 BPS) HSP90. Binding was determined by calculating the interaction shift of HSP90 isoforms with FITC-labeled geldanamycin (a first-generation panHSP90 inhibitor). In a 96-well plate, each compound was added using a Tecan D300E at different concentrations, ranging from 0.01 μM to 100 μM. FITC-labeled geldanamycin and alpha or beta HSP90 were then added, and the plates were analyzed using an EnVision multimode plate reader.

[00174] Results: The IC50 values ​​of competitive binding were calculated based on a concentration-response test for individual compounds and are Petition 870250083412, dated 09 / 16 / 2025, pp. 91 / 105 74 / 79 summarized in Table 2. Table 2 Compound HSP90 alpha IC50 (μM) HSP90 beta IC50 (μM) 001 0.04 0.09 002 0.12 0.15 003 0.06 0.12 004 0.45 1.9 005 0.88 0.83 006 0.6 1.15 Debio0932 0.09 0.16

[00175] Conclusion: The compounds of the invention show binding to the alpha and beta isoforms of HSP90 of at least the same order as the reference compound Debio0932 or even improved in some cases. Example 2: Thermal shock response (HSR)

[00176] Purpose: One of the main activities of N-terminal HSP90 inhibitors, such as those of the present invention, is to trigger the heat shock response (HSR), mainly distinguished by the upregulation of HSP70 caused by binding to HSP90 by the inhibitor.

[00177] Material and method: MCF-7 cells were treated with Debio0932 or a compound according to the invention at 10 μM and incubated for 24 hours. The lysates Petition 870250083412, dated 09 / 16 / 2025, pp. 92-105 75 / 79 cells were then prepared in RIPA buffer and each condition was analyzed by western blot analysis for HSP70 expression. GAPDH was used as a charge control. The effect of each compound on HSP70 induction was evaluated as the HSP70 signal ratio compared to GAPDH.

[00178] Results: The HSP70 levels at 10 μM (i.e., HSP70 to GAPDH signal ratios) are summarized in Table 3. Table 3 Compound Level HSP70 (10 μM) 001 4.2 002 3.23 003 1.79 Debio0932 1.85

[00179] Conclusion: Treatment of cells with a compound according to the invention led to HSP70 expression of at least the same order as the reference compound Debio0932 or even improved in some cases, showing that the compounds of the invention trigger a strong HSR. Example 3: Metabolism - CYP inhibition profile

[00180] Purpose: Analysis of cytochrome P450 enzyme inhibition is used to predict the interaction Petition 870250083412, dated 09 / 16 / 2025, pp. 93-105 76 / 79 pharmacological interaction with CYP enzymes, as this interaction predicts the metabolism of the compound. In vitro inhibition of the 5 major cytochrome P450 isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4-M) was evaluated for the compounds of the invention and for the reference compound Debio0932 by LC-MS / MS.

[00181] Material and method: Specific CYP isoform substrates are incubated individually with human or mouse liver microsomes and a concentration range (0.05 - 50 μM) of the tested compounds or known CYP inhibitors used as controls. After a 10-minute incubation at 37°C, metabolite formation is monitored by LC-MS / MS.

[00182] Results: The IC50 (μM) values ​​were calculated based on a concentration-response test for the individual compounds and are summarized in Table 4. Table 4 Compound CYP1A2 CYP2C9 CYP2C19 CYP2D6 CYP3A4 001 50 50 50 50 50 002 50 50 50 50 26.1 003 50 50 50 50 5.12 004 50 50 17.8 0.24 6.1 Debio0932 45.9 4.44 0.843 3.73 16.8 Petition 870250083412, dated 09 / 16 / 2025, pp. 94 / 105 77 / 79

[00183] Conclusion: The compounds of the invention showed an improved CYP inhibition profile (decreased inhibition) compared to the reference compound Debio0932, suggesting that they could have a more stable metabolization profile and therefore improved overall pharmacokinetic properties. Example 4: Metabolism - Microsomal clearance of the liver

[00184] Purpose: Liver microsomal clearance analysis consists of calculating the time it takes for a compound to be degraded in the presence of liver microsomes in order to predict its rate of metabolization and clearance in a living organism. The in vitro clearances of the compounds of the invention and the reference compound Debio0932 were calculated in the presence of human liver microsomes by LC-MS / MS.

[00185] Material and method: Each compound was added to the well containing human microsome preparation and mixed. The plates were then incubated at 37°C for different time points before the addition of quenching solution to stop the reaction. The plates were then sealed and shaken for 10 minutes before LC-MS / MS analysis.

[00186] Results: The predicted intrinsic liver clearance CLint(liver) (mL / min / kg) was calculated for each Petition 870250083412, dated 09 / 16 / 2025, pages 95 / 105 78 / 79 compounded with the following formula: C -Cvt -v0Cwhen Ct= —Cn, _ L112 _ 0.69311 ' 2 - -j — —j kekeρτ _ o.693 ,1 111 Vitro 1} ,· 2 mg / mL of microsomal protein in the reaction system emg of microsomes * g of liver lnt(mic) g of liver kg of body weight where: Co is the concentration of the test compound at time t = 0; Ct is the concentration of the test compound at time t (min); ke is the elimination rate constant; t is the point in time of measurement (min); CLint (mic) (mL / min / mg of microsomes) is the intrinsic clearance in vitro, in the presence of hepatic microsomes; CLint (liver) (mL / min / kg) is the predicted intrinsic clearance in vivo.

[00187] The results in Table 5 are expressed as a percentage of Debio0 932 CLint(liver) (mL / min / kg) . Table 5 Compound CLint (liver) as a percentage of Debio 0932 DebioO 932 100.00 Petition 870250083412, dated 09 / 16 / 2025, pp. 96 / 105 79 / 79 001 48.54 002 60.63 003 55.74 004 38.78 005 77.74 006 83.80

[00188] Conclusion: The compounds of the invention showed an improved microsomal clearance profile (enhanced CLint(iiver)), compared to the reference compound Debio0932, suggesting that they could have a more stable metabolization profile and therefore improved overall pharmacokinetic properties. Petition 870250083412, dated 09 / 16 / 2025, pp. 97 / 105

Claims

1 / 7 CLAIMS 1. Compound of formula (I): (I) or a pharmaceutically acceptable salt and / or solvate thereof, characterized in that: X1 is N or CH; X2 is N or CH; provided that X1 and X2 are not both N; Y is S, SO, SO2, NH, O or CH2; L1 is a C1-4 alkyl; R1 is a C1-8 alkyl; R1' is H or C1-4 alkyl; n is equal to 1 or 2. R2 and R2' are each independently H, D, methyl or halo; A is NR3R3', OR3 or SO2R3; where: R3 is cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, alkenyl, C1-4 haloalkyl, cyanoalkyl, cyanocarbonyl, aminocarbonylalkyl; in which the cycloalkyl and heterocyclyl portions are optionally Petition 870250083412, dated 09 / 16 / 2025, p.98 / 105 2 / 7 substituted by one or more substituents selected from D, cyano, halo, hydroxyl and C1-4 alkyl; R3' is C1-4 alkyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, alkenyl, C1-4 haloalkyl, cyanoalkyl, cyanocarbonyl, aminocarbonylalkyl; wherein the cycloalkyl and heterocyclyl portions are optionally substituted by one or more substituents selected from D, cyano, halo, hydroxyl, and C1-4 alkyl; preferably, R3' is C1-4 alkyl; more preferably, R3' is methyl.

2. Compound according to claim 1, characterized in that X1 and X2 are both CH or X1 is N and X2 is CH.

3. Compound according to claim 1 or claim 2, characterized in that Y is S, SO or NH, preferably Y is S.

4. A compound according to any one of claims 1 to 3, characterized in that n equals 1 and R2 and R2' are both H or both F.

5. Compound according to any one of claims 1 to 4, characterized in that L1 is ethyl, R1 is neopentyl and R1' is H.

6. Compound according to any one of claims 1 to 5, characterized in that A is NR3R3', wherein R3 is cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, alkenyl or C1-4 haloalkyl; and R3' is C1-4 alkyl; in a preferred manner, wherein R3 is cycloalkyl, cycloalkylalkyl, alkenyl or C1-4 haloalkyl; and R3' is C1-4 alkyl.

7. Compound according to any one of claims 1 to 6, characterized in that R3 is of formula (i): U^-R4^ R4 r4 , . , K (i) where Z is CH or N; Each R4 is independently H, D, cyano, halo, hydroxyl or C1-4 alkyl; m is equal to 0, 1, 2 or 3; p is equal to 1, 2, 3 or 4; and represents the point of attachment to the rest of the compound.

8. Compound according to any one of claims 1 to 6, characterized in that R3 is an alkenyl or C1-4 haloalkyl; preferably, R3 is an allyl or difluoroethyl.

9. Compound according to any one of claims 1 to 8, characterized in that it is selected from: 2-((6(cyclopropylmethyl)(methyl)amino)benzo[d][1,3]dioxol-5yl)thio)-1-(2-(neopentylamino)ethyl)-1H-imidazo[4,5c]pyridin-4-amine; 8-((6((cyclopropylmethyl)(methyl)amino)benzo[d][1,3]dioxol-5yl)thio)-9-(2-(neopentylamino)ethyl)-9H-purin-6-amine; 8-((6-(allyl(methyl)amino)benzo[d][1,3]dioxol-5-yl)thio)9-(2-(neopentylamino)ethyl)-9H-purin-6-amine; 8 - ((6-(allyl(methyl)amino)-2,2difluorobenzo[d][1,3]dioxol-5-yl)thio)-9-(2(neopentylamino)ethyl)-9H-purin-6-amine; 2-((6-((2,2difluoroethyl)(methyl)amino)benzo[d][1,3]dioxol-5-yl)thio)-1(2-(neopentylamino)ethyl)-1H-imidazo[4,5-c]pyridin-4-amine; 2-((6-(cyclobutyl(methyl)amino)benzo[d][1,3]dioxol-5yl)thio)-1-(2-(neopentylamino)ethyl)-1H-imidazo[4,5c]pyridin-4-amine; and the pharmaceutically acceptable salt and / or solvate thereof.

10. Pharmaceutical composition, characterized in that it comprises a compound, as defined in any one of claims 1 to 9, or a pharmaceutically acceptable salt and / or solvate thereof and at least one pharmaceutically acceptable carrier.

11. Compound, according to any of the claims 1 to 9, or a pharmaceutically acceptable salt and / or solvate thereof, characterized in that it is for use as a medicament.

12. A compound, according to any one of claims 1 to 9, or a pharmaceutically acceptable salt and / or solvate thereof, characterized in that it is for use in the treatment of cancers, neurodegenerative diseases, neurodegenerative diseases with protein aggregates, infectious diseases, ROHHAD (Rapid Onset Obesity with Hypothalamic Dysfunction, Hypoventilation and Autonomic Dysregulation), diabetic atherosclerosis, severe psoriasis, primary myelofibrosis and acute pancreatitis.

13. Compound for use according to claim 12, characterized in that the cancer is selected from among brain tumors, hematopoietic disorders, breast cancer, lung cancer, leukemia, lymphoma, pancreatic cancer, multiple myeloma, prostate cancer, glioma, colon cancer, gastric cancer, ovarian cancer and any cancer with oncogene production controlled by HSP90.

14. Compound for use according to claim 12, characterized in that the neurodegenerative disease is selected from among Alzheimer's disease, senile dementia of the Alzheimer type, dementia by Petition 870250083412, dated 09 / 16 / 2025, page. 102 / 105 6 / 7 head trauma and diffuse brain damage, pugilistic dementia, frontal lobe dementia, Pick's disease, Huntington's disease, multiple system atrophy combining dementia with ataxia and / or manifestations of Parkinson's disease, progressive supranuclear palsy, diffuse Lewy body disease, corticobasal degeneration, Hallervorden-Spatz disease, progressive familial myoclonic epilepsy, Parkinson's disease, striatonigral degeneration, progressive supranuclear palsy, torsion dystonia, spasmodic torticollis, familial tremor, Gilles de la Tourette syndrome, cerebellar cortical degeneration, olivopontocerebellar atrophy, spinocerebellar degeneration, Shy-Drager syndrome, amyotrophic lateral sclerosis,Spinal muscular atrophy, spinal and bulbar muscular atrophy (Kennedy's disease), primary lateral sclerosis, hereditary spastic paraplegia, neural muscular atrophy, chronic familial polyneuropathies, peroneal muscular atrophy, hypertrophic interstitial polyneuropathy, retinitis pigmentosa, hereditary optic atrophy, and Leber amaurosis.

15. Compound for use according to claim 12, characterized in that the neurodegenerative disease with protein aggregates is selected from congenital central hypoventilation syndrome (CCHS), Huntington's disease (HTT), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), synucleinopathies and central hypoventilation syndrome (CHS). Petition 870250083412, dated 09 / 16 / 2025, pp. 103 / 105 7 / 7