Cyclohexyl or heterocycloalkyl beta-hydroxy alkyl amines for use in the treatment of hyperglycemia and disorders characterized by hyperglycemia.

Description

1 / 93 Cyclohexyl or heterocycloalkyl beta-hydroxy alkyl amines for use in the treatment of hyperglycemia and disorders characterized by hyperglycemia. FIELD OF THE INVENTION

[0001] The present invention relates to novel compounds and compositions and their use in medicine, such as in the treatment of hyperglycemia and disorders characterized by hyperglycemia, such as type 2 diabetes. In particular, the invention relates to novel compounds, compositions, and methods for treating conditions such as type 2 diabetes through the activation of the β2-adrenergic receptor. It is important to note that these compounds are believed to have a beneficial side effect profile, as they do not exert their effect through the significant release of cAMP. These compounds are also useful in the treatment of other diseases or disorders whose treatment is mediated by the activation of the β2-adrenergic receptor. BACKGROUND OF THE INVENTION

[0002] The listing or discussion of any document apparently published previously in this descriptive report should not necessarily be taken as an acknowledgment that the document is part of the state of the art or is common general knowledge.

[0003] Hyperglycemia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. If left untreated, hyperglycemia can be a serious problem, potentially leading to life-threatening conditions such as ketoacidosis. For example, chronic hyperglycemia can cause heart damage and is strongly associated with heart attacks and death in individuals without coronary artery disease or a history of heart failure. There are several causes of hyperglycemia, including diabetes and severe insulin resistance.

[0004] Severe insulin resistance (SIR) is a condition in which the patient has very low levels (or, in extreme cases, no significant response) to insulin. There are several syndromes characterized by SIR, Petition 870250102326, dated 07 / 11 / 2025, page 9 / 101 2 / 93 including Rabson-Mendenhall syndrome, Donohue syndrome (leprechaunism), Type A and Type B insulin resistance syndromes, HAIR-AN syndrome (hyperandrogenism, insulin resistance, and acanthosis nigricans), pseudoacromegaly, and lipodystrophy. Most of these conditions have genetic causes, such as mutations in the insulin receptor gene. The prevalence of Donohue syndrome, Rabson-Mendenhall syndrome, and type A insulin resistance syndrome ranges from about 50 recorded cases to 1 in 100,000. However, because some diseases are severe and extremely rare, it is likely that many patients will not be diagnosed before death, especially in less developed areas of the world. Therefore, it is difficult to assess the exact number of patients with these syndromes.

[0005] The current standard for treating hyperglycemia in patients with IBS is a controlled diet, supplemented with medications that affect insulin receptor sensitivity, such as metformin, or insulin supplementation. However, particularly in disorders caused by mutations in the insulin receptor gene, this treatment is not sufficiently effective and often fails.

[0006] Diabetes comprises two distinct diseases, type 1 (or insulin-dependent diabetes) and type 2 (insulin-independent diabetes), both involving malfunction of glucose homeostasis. Type 2 diabetes affects more than 400 million people worldwide, and this number is rapidly increasing. Complications of type 2 diabetes include serious cardiovascular problems, kidney failure, peripheral neuropathy, blindness, and, in the most advanced stages of the disease, even limb loss and ultimately death. Type 2 diabetes is characterized by insulin resistance in skeletal muscle and adipose tissue, and currently there is no definitive cure. Most treatments currently used focus on remedying dysfunctional insulin signaling or inhibiting glucose production by the liver, but many of these treatments have several disadvantages and side effects.Therefore, there is great interest in identifying new insulin-independent forms of treatment for type 2 diabetes. Petition 870250102326, dated 07 / 11 / 2025, page 10 / 101 3 / 93

[0007] In type 2 diabetes, the insulin signaling pathway is reduced in peripheral tissues, such as adipose tissue and skeletal muscle. Treatment methods for type 2 diabetes typically include lifestyle changes as well as insulin injections or oral medications to regulate glucose homeostasis. People with type 2 diabetes in the more advanced stages of the disease develop "beta cell insufficiency," meaning the inability of the pancreas to release insulin in response to high blood glucose levels. In the more advanced stages of the disease, patients usually need insulin injections in combination with oral medications to control their diabetes. Furthermore, the most common medications have side effects that include downregulation or desensitization of the insulin pathway and / or promotion of lipid modality in adipose tissue, liver, and skeletal muscle.Therefore, there is great interest in identifying new ways to treat metabolic diseases, including type 2 diabetes, that do not include these side effects.

[0008] After a meal, the increase in blood glucose levels stimulates the release of insulin by the pancreas. Insulin mediates the normalization of blood glucose levels. Important effects of insulin on glucose metabolism include facilitating glucose uptake in skeletal muscle and adipocytes and increasing glycogen storage in the liver. Skeletal muscle and adipocytes are responsible for insulin-mediated glucose uptake and utilization in the fed state, making them very important sites for glucose metabolism.

[0009] The downstream signaling pathway of the insulin receptor has been difficult to understand in detail. In summary, the control of glucose uptake by insulin involves the activation of the insulin receptor (IR), the insulin receptor substrate (IRS), phosphoinositide 3-kinase (PI3K), and therefore the stimulation of phosphatidylinositol (3,4,5)-triphosphate (PIP3), the mammalian target of rapamycin (also called the mechanistic target of rapamycin, mTOR), Akt / PKB (Akt), and TBC1D4 (AS160), leading to the translocation of glucose transporter 4 (GLUT4) to the plasma membrane. Akt activation is considered necessary Petition 870250102326, dated 07 / 11 / 2025, page 11 / 101 4 / 93 for the GLUT4 translocation.

[0010] It should be noted that skeletal muscles constitute the majority of mammalian body weight and have a vital function in regulating systemic glucose metabolism, being responsible for up to 85% of glucose disposal throughout the body. Glucose uptake in skeletal muscles is regulated by several intra- and extracellular signals. Insulin is the best-studied mediator, but others also exist. For example, AMP-activated kinase (AMPK) functions as an energy sensor in the cell, which can increase glucose uptake and fatty acid oxidation. Due to the large influence that skeletal muscles have on glucose homeostasis, it is plausible that additional mechanisms exist. In light of the increasing prevalence of type 2 diabetes, it is of great interest to find and characterize new insulin-independent mechanisms to increase glucose uptake in muscle cells.

[0011] Blood glucose levels can be regulated by both insulin and catecholamines, but they are released into the body in response to different stimuli. While insulin is released in response to increased blood sugar levels (for example, after a meal), epinephrine and norepinephrine are released in response to various internal and external stimuli, such as exercise, emotions, and stress, and also to maintain tissue homeostasis. Insulin is an anabolic hormone that stimulates many processes involved in growth, including glucose uptake, glycogen formation, and triglycerides, while catecholamines are primarily catabolic.

[0012] Although insulin and catecholamines normally have opposing effects, they have been shown to have similar actions on glucose uptake in skeletal muscle (Nevzorova et al., Br. J. Pharmacol, 137, 9, (2002)). In particular, catecholamines have been reported to stimulate glucose uptake via adrenergic receptors (Nevzorova et al., Br. J. Pharmacol, 147, 446, (2006); Hutchinson, Bengtsson, Endocrinology 146, 901, (2005)) to provide muscle cells with an energy-rich substrate. Therefore, it is likely that in mammals, including humans, the adrenergic and insulin systems may interact. Petition 870250102326, dated 07 / 11 / 2025, p. 12 / 101 5 / 93 function independently to regulate the energy needs of skeletal muscle in different situations. Since insulin also stimulates many anabolic processes, including some that promote undesirable effects, such as the stimulation of lipid modality in tissues, leading, for example, to obesity, it would be beneficial to be able to stimulate glucose uptake by other means, for example, by stimulating adrenergic receptors (ARs).

[0013] All ARs are G protein-coupled receptors (GPCRs) located in the cell membrane and characterized by an extracellular N-terminus, followed by seven transmembrane α-helices (TM-1 to TM-7) connected by three intracellular loops (IL-1 to IL-3) and three extracellular loops (EL-1 to EL-3), and finally, an intracellular C-terminus. There are three different classes of ARs, with distinct expression patterns and pharmacological profiles: αι-, α2-, and β-ARs. αι-ARs comprise the subtypes αίA, Oib, and oid, while α2-ARs are divided into α2A, α2B, and α2O. Beta receptors (β-ARs) are also divided into β1, β2, and β3 subtypes, of which β2-AR is the main isoform in skeletal muscle cells. ARs are G protein-coupled receptors (GPCRs) that signal via classic secondary messengers such as cyclic adenosine monophosphate (cAMP) and phospholipase C (PLC).

[0014] Many effects that occur downstream of ARs in skeletal muscles have been attributed to classical secondary messenger signaling, such as increased cAMP levels, PLC activity, and calcium levels. Stimulation involving classical secondary messengers has many effects on different tissues. For example, it increases heart rate, blood flow, airflow in the lungs, and glucose release from the liver, which can be detrimental or considered an undesirable side effect if AR stimulation is considered a treatment for type 2 diabetes. Adverse effects of classical AR agonists include, for example, tachycardia, palpitations, tremors, sweating, agitation, and increased blood glucose levels (glucose production by the liver).Therefore, it would be beneficial to be able to activate ARs without activating these classic secondary messengers, such as cAMP, to increase glucose uptake in peripheral tissues without stimulating unwanted side effects. Petition 870250102326, dated 07 / 11 / 2025, page 13 / 101 6 / 93

[0015] Glucose uptake is primarily stimulated by facilitative glucose transporters (GLUTs) that mediate glucose uptake in most cells. GLUTs are transporter proteins that mediate the transport of glucose and / or fructose across the plasma membrane down the concentration gradient. There are fourteen known members of the GLUT family, designated GLUT1-14, divided into three classes (Class I, Class II, and Class III) depending on substrate specificity and tissue expression. GLUT1 and GLUT4 are the most intensively studied isoforms and, along with GLUT2 and GLUT3, belong to Class I, which primarily transports glucose (in contrast to Class II, which also transports fructose). GLUT1 is ubiquitously expressed and is responsible for basal glucose transport. GLUT4 is expressed only in peripheral tissues such as skeletal muscle, cardiac muscle, and adipose tissue.It has also been reported that GLUT4 is expressed, for example, in the brain, kidneys, and liver. GLUT4 is the main isoform involved in insulin-stimulated glucose uptake. The mechanism by which insulin signaling increases glucose uptake occurs primarily through the translocation of GLUT4 from intracellular storage to the plasma membrane. GLUT4 translocation is known to be induced by stimulation of the β2-adrenergic receptor.

[0016] Thus, a possible treatment for a condition involving dysregulation of glucose homeostasis or glucose uptake in a mammal, such as type 2 diabetes, would involve activation of the β2-adrenergic receptor, leading to translocation of GLUT4 to the plasma membrane and promotion of glucose uptake in skeletal muscle, leading to normalization of glucose homeostasis throughout the body. Furthermore, it would be advantageous if the treatment did not involve signaling via cAMP, as this would lead to a favorable side effect profile. DESCRIPTION OF THE INVENTION

[0017] It has now been surprisingly discovered that certain cyclohexyl or heterocycloalkyl beta-hydroxyalkyl amines that act as agonists at the β2-adrenergic receptor increase glucose uptake in Petition 870250102326, dated 07 / 11 / 2025, page 14 / 101 7 / 93 skeletal muscle.

[0018] Furthermore, it was found that this effect is not mediated by a significant release of cAMP, so many of the commonly described side effects observed with traditional β2-adrenergic agonists (e.g., tachycardia, palpitations, tremor, sweating, agitation, and the like) can be reduced.

[0019] The use of such compounds in medicine represents a promising strategy for the treatment of conditions described in this document, such as those characterized by high blood sugar levels (i.e., hyperglycemia), such as type 2 diabetes. COMPOUNDS OF THE INVENTION

[0020] In a first aspect of the invention, a compound of formula I is provided, Q Q5 Q5Q4Q Q2( Q3OHHR1Nψ-> ÇA)~(Z)n I

[0021] or a pharmaceutically acceptable salt thereof, where:

[0022] R1 represents H or Ci—6 alkyl;

[0023] each of Q1a Q5 independently represents carbon, a heteroatom, or a direct bond, so the ring comprising Q1a Q5 represents:

[0024] plus Y1, or

[0025] replaced by one or more Y2;

[0026] CN, -N3, -N(Rb1)Rc1 or -ORd1;

[0027] a phenyl optionally replaced by a 5- or 6-membered heteroaryl, optionally each Y1 independently represents halo, Ra1, each Y2 independently represents halo, Ra2, Petition 870250102326, dated 07 / 11 / 2025, p. 15 / 101 8 / 93 CN, -N3, -N(Rb2)Rc2 or -ORd2;

[0028] ring A represents a 4- to 7-membered cycloalkyl or a 4- to 7-membered heterocycloalkyl with one or two heteroatoms selected from N or O;

[0029] n represents 0 to 5;

[0030] when present on a carbon atom, each Z independently represents halo, Ra3, -CN, -N3, -N(Rb3)Rc3, -ORd3, -S(O)pRe3, S(O)qN(Rf3)Rg3, -N(Rh3)S(O)tRi3, or =O;

[0031] when present in a nitrogen atom, each Z independently represents Ra3, -S(O)pRe3 or -S(O)qN(Rf3)Rg3;

[0032] each Ra1 and Ra2, independently represents C1-6 alkyl optionally substituted by one or more halos;

[0033] each Ra1 and Ra2, independently represents C1-6 alkyl optionally substituted by one or more halos;

[0034] each Ra3, Re3 and Ri3 independently represents C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, each optionally substituted by one or more groups selected independently from halo and G1;

[0035] each Rb1, Rb2, Rb3, Rc1, Rc2, Rc3, Rd1, Rd2, Rd3, Rf3, Rg3 and Rh3 independently represents

[0036] H, or

[0037] C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, each optionally substituted by one or more groups selected independently from halo and G2;

[0038] or, alternatively, any of the Rb3 and Rc3, and / or Rf3 and Rg3 may be linked together to form, together with the nitrogen atom to which they are attached, a 4- to 6-membered ring, which ring optionally contains one more heteroatom and which ring is optionally substituted by one or more halo-selected groups, C1-3 alkyl optionally substituted by one or more halos and =O;

[0039] each G1 and G2 independently represents Ra4, Petition 870250102326, dated 07 / 11 / 2025, p. 16 / 101 9 / 93 CN, -N3, -N(Rb4)Rc4, -ORd4, -S(O)pRe4, -S(O)qN(Rf4)Rg4, -N(Rh4)S(O)rRi4or =O;

[0040] each Ra4 independently represents 5- or 6-membered phenyl or heteroaryl groups, each optionally substituted by one or more selected halo, Ra5, -CN, -N3, -N(Rb5)Rc5, -ORd5, -S(O)pRe5, S(O)qN(Rf5)Rg5, or -N(Rh5)S(O)tRi5 groups;

[0041] each Rb4, Rc4, Rd4, Rf4, Rh4 and Rg4 independently represents H, or C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl optionally substituted with one or more halos, -CN or =O;

[0042] each Re4e Ri4 independently represents C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, each optionally substituted by one or more halo or -CN;

[0043] or, alternatively, any of the Rb4e Rc4e / or Rf4e Rg4 can be linked to form, together with the nitrogen atom to which they are attached, a 4- to 6-membered ring, which optionally contains one more heteroatom and which is optionally substituted by one or more halo-selected groups, C1-3 alkyl optionally substituted by one or more halos and =O;

[0044] each Ra5, Re5, and Ri5 independently represents C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, each optionally substituted with one or more halo groups selected independently from C1-3 alkyl optionally substituted with one or more halo groups and =O;

[0045] each Rb5, Rc5, Rd5, Rf5, Rg5 and Rh5 independently represents

[0046] H, or

[0047] C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, each optionally substituted with one or more halo groups selected independently from among, C1-3 alkyl optionally substituted with one or more halo groups and =O;

[0048] or, alternatively, any of the Rb5e Rc5, and / or Rf5e Rg5 can be linked together to form, together with the nitrogen atom to which they are attached, a 4- to 6-membered ring, which ring contains, Petition 870250102326, dated 07 / 11 / 2025, p. 17 / 101 10 / 93 optionally, plus one heteroatom and which is optionally replaced by one or more halo-selected groups, C1-3 alkyl optionally replaced by one or more halos and =O;

[0049] each p independently represents 0, 1 or 2;

[0050] each q independently represents 1 or 2;

[0051] each r independently represents 1 or 2; and

[0052] each t independently represents 1 or 2,

[0053] these compounds (including pharmaceutically acceptable salts) may be referred to in this document as “compounds of the invention”.

[0054] For the avoidance of doubt, the expert will understand that references herein to compounds of particular aspects of the invention (such as the first aspect of the invention, for example, compounds of formula I) will include references to all embodiments and particular features thereof, which embodiments and particular features may be taken in combination to form additional embodiments.

[0055] Unless otherwise indicated, all technical and scientific terms used herein have the same meaning commonly understood by a person skilled in the art to which this invention relates.

[0056] Pharmaceutically acceptable salts include acid addition salts and base addition salts. Such salts may be formed by conventional means, for example, by reacting a free acid or a free base form of a compound of the invention with one or more equivalents of an appropriate acid or base, optionally in a solvent or medium in which the salt is insoluble, followed by removal of said solvent or medium using standard techniques (e.g., in vacuo, by lyophilization or by filtration). The salts may also be prepared by exchanging a counter-ion of a compound of the invention in the form of a salt with another counter-ion, for example, using a suitable ion exchange resin.

[0057] Specific acid addition salts that may be mentioned include carboxylate salts (e.g., formate, acetate, trifluoroacetate, propionate, isobutyrate, heptanoate, decanoate, caprate, caprylate, Petition 870250102326, dated 07 / 11 / 2025, page 18 / 10111 / 93 stearate, acrylate, caproate, propiolate, ascorbate, citrate, glucuronate, glutamate, glycolate, α-hydroxybutyrate, lactate, tartrate, hemitartrate, phenylacetate, mandelate, phenylpropionate, phenylbutyrate, benzoate, chlorobenzoate, methylbenzoate, hydroxybenzoate, methoxybenzoate, dinitrobenzoate, o-acetoxybenzoate, salicylate, nicotinate, isonicotinate, cinnamate, oxalate, malonate, succinate, suberate, sebacate, fumarate, malate, maleate, hydroxymaleate, hippurate, phthalate or terephthalate salts), halide salts (e.g., hydrochloride, hydrobromide or iodide salts), sulfonate salts (e.g., benzenesulfonate, methyl-, bromo- or chlorobenzenesulfonate, xylenesulfonate, methanesulfonate, ethanesulfonate, propanesulfonate, hydroxyethanesulfonate, salts of 1- or 2-naphthalenesulfonate or 1,5-naphthalenedisulfonate) or salts of sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate,pyrophosphate or nitrate and similar substances.

[0058] The versed person will understand that the term “hemi” used here in relation to a hemitartrate salt of a compound of formula I means that the stoichiometry between the compound of formula I and the tartrate in the salt is 1:0.5 (i.e., equivalent to 2:1).

[0059] Specific base addition salts that can be mentioned include salts formed with alkali metals (such as Na and K salts), alkaline earth metals (such as Mg and Ca salts), organic bases (such as ethanolamine, diethanolamine, triethanolamine, tromethamine, and lysine), and inorganic bases (such as ammonia and aluminum hydroxide). More particularly, base addition salts that can be mentioned include Mg, Ca, and, more particularly, K and Na salts.

[0060] Among the pharmaceutically acceptable salts that can be mentioned are hydrochloride or acetate salts, such as acetate salts.

[0061] More specific pharmaceutically acceptable salts that may be mentioned include hydrochloride salts.

[0062] For the avoidance of doubt, the compounds of the first aspect of the invention may exist as solids and, therefore, the scope of the invention Petition 870250102326, dated 07 / 11 / 2025, p. 19 / 101 12 / 93 includes all its amorphous, crystalline and partially crystalline forms, and may also exist as oils. When the compounds of the first aspect of the invention exist in crystalline and partially crystalline forms, such forms may include solvates, which are included within the scope of the invention. The compounds of the first aspect of the invention may also exist in solution.

[0063] The compounds of the first aspect of the invention may contain double bonds and therefore may exist as geometric isomers E (entgegen) and Z (zusammen) with respect to each individual double bond. All such isomers and mixtures thereof are included within the scope of the invention.

[0064] The compounds of the first aspect of the invention may also exhibit tautomerism. All tautomeric forms and mixtures thereof are included within the scope of the invention.

[0065] The compounds of the first aspect of the invention may also contain one or more asymmetric carbon atoms and therefore may exhibit optical diastereoisomerism and / or diastereoisomerism. The diastereoisomers can be separated using conventional techniques, for example, chromatography or fractional crystallization. The various stereoisomers (i.e., enantiomers) can be isolated by separating a racemic or other mixture of the compounds using conventional techniques, for example, fractional crystallization or HPLC.Alternatively, the desired optical isomers can be obtained from suitable optically active starting materials under conditions that will not cause racemization or epimerization (i.e., a “chiral pool” method), by reacting the suitable starting material with a “chiral auxiliary” that can be subsequently removed at a suitable stage by derivatization (i.e., resolution, including dynamic resolution); for example, with a homochiral acid followed by separation of the diastereomeric derivatives by conventional means such as chromatography, or by reaction with a suitable chiral reagent or chiral catalyst, all under conditions known to the skilled professional. All stereoisomers and mixtures thereof are included within the scope of the invention.

[0066] As used in this document, the references Petition 870250102326, dated 07 / 11 / 2025, page 20 / 101 13 / 93 halo and / or halogen groups refer independently to fluoro, chlorine, bromine and iodine (e.g., fluoro (F) and chlorine (Cl), as F).

[0067] Unless otherwise specified, the C1-z alkyl groups (where z is the upper limit of the range) defined herein may be straight-chain or, when there are a sufficient number (i.e., at least three) of carbon atoms, be branched-chain and / or cyclic (thus forming a C3-z-cycloalkyl group). When there are a sufficient number (i.e., a minimum of four) of carbon atoms, these groups may also be partially cyclic. Some examples of cyclic alkyl groups include cyclopropylmethyl and cyclohexylethyl. When there are a sufficient number of carbon atoms, these groups may also be multicyclic (e.g., bicyclic or tricyclic) or spirocyclic.

[0068] To avoid confusion, alkyl groups can be linear (also called linear chain), branched (also called branched chain) and / or cyclic. More specifically, alkyl groups can be linear (also called linear chain) or branched (also called branched chain).

[0069] Unless otherwise specified, the C2-z alkenyl groups (where z is the upper limit of the range) defined herein may be straight-chain or, when there are a sufficient number (i.e., at least three) of carbon atoms, branched-chain.

[0070] Unless otherwise specified, the C2-z alkynyl groups (where z is the upper limit of the range) defined herein may be straight-chain or, where there are a sufficient number (i.e., a minimum of four) of carbon atoms, may be branched-chain.

[0071] To avoid doubt, the specialist will understand that the term alkyl refers to varieties of saturated hydrocarbons, while the term alkenyl refers to varieties of unsaturated hydrocarbons containing at least one carbon-carbon double bond and the term alkynyl refers to varieties of unsaturated hydrocarbons containing at least one carbon-carbon triple bond. Petition 870250102326, dated 07 / 11 / 2025, page 21 / 101 14 / 93 carbon.

[0072] As used herein, the term heterocyclyl may refer to non-aromatic monocyclic and bicyclic heterocyclyl groups (groups that may be further bridged) in which at least one (e.g., from one to four) of the atoms in the ring system is other than carbon (i.e., a heteroatom), and in which the total number of atoms in the ring system is between three and twelve (e.g., between five and ten and, more preferably, between three and eight, e.g., a 5- or 6-membered heterocyclyl group). Furthermore, these heterocyclyl groups can be saturated, forming a heterocycloalkyl, or unsaturated, containing one or more carbon-carbon double and / or triple bonds or, where possible, carbon-heteroatom or heteroatom-heteroatom, forming, for example, a C2-Z heterocycloalkenyl (e.g., C4-z) (where z is the upper limit of the range) or a C7-Z heterocycloalkynyl group. C2-Z heterocyclic groups that can be mentioned include 7-azabicyclo-[2.2.1]heptanyl, 6azabicyclo[3.1.1]heptanyl, 6-azabicyclo[3.2.1]-octanyl, 8-azabicyclo[3.2.1]octanyl, aziridinyl, azetidinyl, 2,3-dihydroisothiazolyl, dihydropyranyl, dihydropyridinyl, dihydropyrrolyl (incl. 2,5-dihydropyrrolyl), dioxolanil (incl. 1,3-dioxolanil), dioxanil (including 1,3-dioxanyl and 1,4-dioxanyl), dithianyl (including 1,4-dithianyl), dithiolanil (including 1,3-dithiolanil), imidazolidinyl, imidazolinyl, isothiazolidinyl, morpholinyl, 7-oxabicyclo[2.2.1]heptanyl, 6-oxabicyclo[3.2.1]-octanyl, oxetanil, oxiranil, piperazinyl, piperidinyl, pyranyl, pyrazolidinyl, pyrrolidinonyl, pyrrolidinyl, pyrrolinyl, quinuclidinyl, sulfonyl, 3-sulfolenyl, tetra-hydropyranyl, tetra-hydrofuryl, tetra-hydropyridinyl (as 1,2,3,4-tetrahydropyridinyl and 1,2,3,6-tetrahydropyridinyl), thianyl, thiiranyl, thiolanyl, tetra-hydrothiopyranil, thiomorpholinyl, trithianyl (including 1,3,5trithianyl), tropanyl and the like.Substituents in heterocyclic groups can, when appropriate, be located on any atom in the ring system, including a heteroatom. Furthermore, in the case where the substituent is another cyclic compound, the cyclic compound can be linked through a single atom in the heterocyclic group, forming a so-called "spiral" compound. The point of attachment of heterocyclic groups can be via any atom in the ring system, including (when appropriate) a heteroatom. Petition 870250102326, dated 07 / 11 / 2025, page 22 / 101 15 / 93 additional heteroatom (such as a nitrogen atom) or an atom in any fused carbocyclic ring that may be present as part of the ring system. Heterocyclic groups may also be in the N- or S-oxidized form.

[0073] As described in this document, ring A represents a 4- to 7-membered cycloalkyl or a 4- to 7-membered heterocycloalkyl with one or two heteroatoms (or just one heteroatom) selected from N (nitrogen) or O (oxygen).

[0074] In some embodiments, when ring A represents a 4- to 7-membered heterocycloalkyl group, ring A does not contain any other heteroatoms in its ring structure, i.e., the only heteroatoms of ring A are selected from N and O.

[0075] In certain embodiments, ring A represents a 4- to 7-membered heterocycloalkyl, as well as a 5- to 6-membered heterocycloalkyl.

[0076] Several heterocycloalkyl groups are well known to those skilled in the art, such as dioxolanyl (including 1,3-dioxolanyl), dioxanyl (including 1,3-dioxanyl and 1,4-dioxanyl), imidazolidinyl, morpholinyl, piperazinyl, piperidinyl (including 2, 3 or 4-piperidinyl), pyrazolidinyl, pyrrolidinonyl, pyrrolidinyl (including 2 or 3-pyrrolidinyl), tetrahydropyranyl, tetrahydrofuryl.

[0077] In certain embodiments, ring A may include a heteroatom selected from O (oxygen) and N (nitrogen). For example, ring A may contain an O (oxygen) or ring A may contain an N (nitrogen).

[0078] In other embodiments, ring A may contain two heteroatoms selected from O (oxygen) and N (nitrogen). For example, ring A may contain two O (oxygen) or two N (nitrogen). Alternatively, ring A may contain one O (oxygen) and one N (nitrogen).

[0079] In certain embodiments, ring A may be a 5- or 6-membered heterocycloalkyl, optionally substituted by one or more (e.g., one) Z.

[0080] In more specific configurations, ring A can be Petition 870250102326, dated 07 / 11 / 2025, p. 23 / 101 16 / 93 a 6-membered heterocycloalkyl, optionally substituted by one or more (e.g., one) Z.

[0081] More specific heterocycloalkyl groups representing ring A that can be mentioned include piperidinyl, such as piperidin-3-yl or piperidin-4-yl (referring to the standard numbering where the N atom represents position 1).

[0082] In certain embodiments, ring A represents a 4- to 7-membered cycloalkyl, as well as a 5- to 6-membered cycloalkyl. In more specific embodiments, ring A represents a 6-membered cycloalkyl (i.e., cyclohexyl).

[0083] For the avoidance of doubt, ring A may be replaced by various Z groups, as defined in this document, as appropriate under the circumstances. The expert will understand that the (maximum) number and position of such substituents will be dictated by the nature of the ring, such as the ring size and the level of saturation thereof. Furthermore, the expert will understand that such substituents may be present in suitable parts comprised within ring A, for example, embodiments, the compounds of suitable parts of C (carbon) or N (nitrogen).

[0084] In certain formula I compounds, there may be formula IX or IY compounds. Q2 Q3OHHR1 Q N. _ Q5 Q5 Q4 Q(Z)n ^)m1 X m2 IXOHH R1 Q2QNxWm3Q§Q5>fm4Q(Z)' IY

[0085] wherein the ring comprising Q1 to Q5, R1, Z and n are defined for compounds of formula I (including all its embodiments), and wherein X represents C (carbon) or N (nitrogen), m1 and m2 independently represent 0 to 2, m3 represents 0 to 3 and m4 represents 0 to 2. Petition 870250102326, dated 07 / 11 / 2025, p. 24 / 101 17 / 93

[0086] In a specific embodiment, the sum of ml and m2 is at least 4.

[0087] In a specific modality, the sum of m3 and m4 is at least 4.

[0088] As described in this document, the ring comprising Q1 to Q5 (which may be called ring Q) represents a 5- or 6-membered phenyl or heteroaryl optionally substituted by one or more Y (i.e., one or more Y1 or Y2).

[0089] In this way, the versed person will understand that Q1a Q5:

[0090] - will each represent carbon atoms, so as to form a phenyl group; or

[0091] - together they will represent carbon atoms, one or more heteroatoms and, when the ring containing Q1a Q5 has 5 members, a direct bond, so as to form suitable heteroaryl groups, as is known to those skilled in the art.

[0092] Thus, the expert will understand that, representing Q1 to Q5, the ring may include, in addition to carbon atoms, one or more heteroatoms, so as to form suitable heteroaryl groups, as known to those skilled in the art. Furthermore, the expert will understand that, when the ring containing Q1 to Q5 has 5 members, one of Q1 to Q5 (for example, Q5) will represent a direct bond (i.e., this group will not be present).

[0093] To avoid doubt, the representation of the ring containing groups Q1 to Q5 with a circle (for example, as in formula I) will be understood as an indication that the ring is aromatic.

[0094] For the avoidance of doubt, as used herein, references to heteroatoms will have their normal meaning as understood by a person skilled in the art. Specific heteroatoms that may be mentioned include phosphorus, selenium, tellurium, silicon, boron, oxygen, nitrogen, and sulfur (e.g., oxygen, nitrogen, and sulfur). Petition 870250102326, dated 07 / 11 / 2025, page 25 / 101 18 / 93

[0095] For the avoidance of doubt, references to polycyclic (e.g., bicyclic or tricyclic) groups (e.g., when used in the context of cycloalkyl groups) refer to ring systems in which at least two cleavages would be required to convert these rings into a linear chain, with the minimum number of such cleavages corresponding to the number of rings defined (e.g., the term bicyclic may indicate that a minimum of two cleavages would be required to convert the rings into a linear chain). For the avoidance of doubt, the term bicyclic (e.g., when used in the context of alkyl groups) may refer to groups in which the second ring of a two-ring system is formed between two adjacent atoms of the first ring, and may also refer to groups in which two non-adjacent atoms are linked by an alkylene group, which may be called a bridge.

[0096] The present invention also encompasses isotopically labeled compounds of the present invention that are identical to those described herein, except that one or more atoms are replaced by an atom with an atomic mass or mass number different from the atomic mass or mass number normally found in nature (or the most abundant found in nature). All isotopes of any particular atom or element, as specified in this document, are contemplated within the scope of the compounds of the invention. Therefore, the compounds of the invention also include deuterated compounds, that is, in which one or more hydrogen atoms are replaced by the hydrogen isotope deuterium.

[0097] To avoid doubt, in cases where the identity of two or more substituents in a compound of the invention may be the same, the actual identities of the respective substituents are by no means interdependent. For example, in the situation where two or more Y groups are present, these Y groups may be the same or different. Similarly, when two or more Y groups are present and each of them represents a halo, the halo groups in question may be the same or different. Likewise, when more than one Ra is present and each independently represents C1-6 alkyl Petition 870250102326, dated 07 / 11 / 2025, p. 26 / 101 19 / 93 replaced by one or more groups G, the identities of each G are by no means interdependent.

[0098] The expert will understand that the compounds of the invention that are the subject of this invention include those that are stable. That is, the compounds of the invention include those that are robust enough to survive isolation, for example, from a reaction mixture, to a useful degree of purity.

[0099] All embodiments of the invention and specific features mentioned herein may be taken individually or in combination with any other embodiments and / or specific features mentioned herein (therefore describing more specific embodiments and specific features, as disclosed herein) without departing from the disclosure of the invention.

[0100] In one specific embodiment, there is the caveat that the compound of formula I is not:

[0101] 4-[[2-(4-amino-3,5-dichlorophenyl)-2hydroxyethyl]amino]cyclohexan-1-ol;

[0102] ^)-α-[[(3Methylcyclobutyl)amino]methyl]benzenemethanol;

[0103] ^)-α-[[(3Methylcyclobutyl)amino]methyl]benzenemethanol;

[0104] α-[[(3-Metilciclobutil)amino]methyl]benzenometanol;

[0105] α-[[(3-Aminociclobutil)amino]metil]benzenometanol;

[0106] ^)-α-[[(3Hidroxiciclobutil)amino]methyl]benzenometanol;

[0107] ^)-α-[[(3Hidroxiciclobutil)amino]methyl]benzenometanol;

[0108] α-[[(3Hidroxiciclobutil)amino]methyl]benzenometanol;

[0109] α-[[(3-Metilciclobutil)amino]metil]-3-piridinametanol;

[0110] α-[[(3-Metilciclobutil)amino]metil]-4-piridinametanol; Petição 870250102326, de 07 / 11 / 2025, pág. 27 / 101 20 / 93

[0111] a-[[(4-Metilciclo-hexil)amino]metil]benzenometanol;

[0112] (aS)-a-[[(3Metilciclopentil)amino]metil]benzenometanol;

[0113] (aR)-a-[[(3Metilciclopentil)amino]metil]benzenometanol;

[0114] a-[[(trans-4-methylcyclohexil)amino]methyl]benzenometanol;

[0115] α-[[(3Aminociclopentil)amino]methyl]benzenometanol;

[0116] a-[[(3-Metilciclopentil)amino]metil]benzenometanol;

[0117] a-[[(3-Metilciclo-hexil)amino]metil]benzenometanol;

[0118] α-[[(3-Aminociclohexil)amino]metil]benzenometanol;

[0119] α-[[(4-Aminociclohexil)amino]metil]benzenometanol;

[0120] a-[[(3-fluorociclobutil)amino]metil]benzenometanol;

[0121] a-[[(3-Metilciclobutil)amino]metil]-2-piridinametanol;

[0122] α-[[(3-Hidroxiciclobutil)amino]metil]-3piridinametanol;

[0123] (aR)-a-[[(3Fluorociclobutil)amino]metil]benzenometanol;

[0124] a-[[(4-Metilciclo-heptil)amino]metil]benzenometanol;

[0125] (aR)-a-[[(1-Metil-3azetidinil)amino]metil]benzenometanol;

[0126] α-[[(1^N-3azetidinil)amino]methyl]benzenometanol;

[0127] ^)-α-[[(1^N-3azetidinil)amino]methyl]benzenometanol;

[0128] α-[[(4-Hidroxiciclohexil)amino]methyl]benzenometanol; Petição 870250102326, de 07 / 11 / 2025, pág. 28 / 101 21 / 93

[0129] a-[[(3-Metilciclopentil)amino]metil]-3piridinametanol;

[0130] α-[[(3-Metilciclopentil)amino]metil]-4piridinametanol;

[0131] α-[[(3-Hidroxiciclobutil)amino]metil]-2piridinametanol;

[0132] α-[[(4-Metilciclo-hexil)amino]metil]-4piridinametanol;

[0133] α-[[(3-Metilciclo-hexil)amino]metil]-4piridinametanol;

[0134] (aR)-a-[[(1-Metil-3pirrolidinil)amino]metil]benzenometanol;

[0135] ^)-α-[[(1^N-3pirrolidinil)amino]methyl]benzenometanol;

[0136] α-[[(1^N-3pirrolidinil)amino]methyl]benzenometanol;

[0137] α-[[(1^N-4piperidinil)amino]methyl]benzenometanol; 5-[(2-Hidroxi-2-feniletil)amino]ciclo-octanol;

[0139] α-[[(3-Fluorociclobutil)amino]metil]-3piridinametanol;

[0140] α-[[(1^N-3piperidinil)amino]methyl]benzenometanol;

[0141] α-[[(1-Metil-3-azetidinil)amino]metil]-3piridinametanol;

[0142] α-[[(Hexahydro-1-methyl-1H-azepin-4yl)amino]methyl]benzenemethanol;

[0143] α-[[(3-Fluorocyclobutyl)amino]methyl]-2-pyridinemethanol; α-[[(1-Methyl-3-pyrrolidinyl)amino]methyl]-4 Petition 870250102326, de 07 / 11 / 2025, p. 29 / 101 22 / 93 pyridinemethanol; α-[[(1-Methyl-3-pyrrolidinyl)amino]methyl]-3-pyridinemethanol;

[0146] cloridrato de α-[[(1-methyl-4-piperidinyl)amino]methyl]benzenemethanol;

[0147] α-[[(1-Methyl-3-azetidinyl)amino]methyl]-2-pyridinemethanol; 2-((1-benzylpiperidin-4-yl)amino)-1-phenylethanol,

[0149] 4-(1-hydroxy-2-((1-methylpiperidin-4-yl)amino)ethyl)phenol, 4-(2-((1-benzylpiperidin-4-yl)amino)-1-hydroxyethyl)phenol,

[0151] 4-(2-((1-butylpiperidin-4-yl)amino)-1-hydroxyethyl)phenol,

[0152] 3-(2-((1-butylpiperidin-4-yl)amino)-1-hydroxyethyl)phenol,

[0153] 4-(1-hydroxy-2-((1-(2-methoxyethyl)piperidin-4yl)amino)ethyl)phenol, or

[0154] 4-(1-hydroxy-2-((1-phenethylpiperidin-4yl)amino)ethyl)phenol.

[0155] In a specific embodiment, there are the caveats (A) to (M) that the compound of formula I is not a compound of any of the following:

[0156] (A)

[0157] 4-[[2-(4-amino-3,5-dichlorophenyl)-2hydroxyethyl]amino]cyclohexan-1-ol;

[0158] (B)

[0159] ^)-α-[[(3Methylcyclobutyl)amino]methyl]benzenemethanol;

[0160] ^)-α-[[(3Methylcyclobutyl)amino]methyl]benzenemethanol;

[0161] α-[[(3-Methylcyclobutyl)amino]methyl]benzenemethanol;

[0162] α-[[(3-Aminocyclobutyl)amino]methyl]benzenemethanol;

[0163] ^)-α-[[(3Petition 870250102326, dated 07 / 11 / 2025, page 30 / 101 23 / 93 Hydroxycyclobutyl)amino]methyl]benzenemethanol;

[0164] (aS)-a-[[(3Hydroxycyclobutyl)amino]methyl]benzenemethanol;

[0165] α-[[(3Hidroxiciclobutil)amino]metil]benzenometanol;

[0166] a-[[(3-Metilciclobutil)amino]metil]-3-piridinametanol;

[0167] a-[[(3-Metilciclobutil)amino]metil]-4-piridinametanol;

[0168] a-[[(4-Metilciclo-hexil)amino]metil]benzenometanol;

[0169] (aS)-a-[[(3Metilciclopentil)amino]metil]benzenometanol;

[0170] (aR)-a-[[(3Metilciclopentil)amino]metil]benzenometanol;

[0171] a-[[(trans-4-Metilciclohexil)amino]metil]benzenometanol;

[0172] α-[[(3Aminociclopentil)amino]metil]benzenometanol;

[0173] a-[[(3-Metilciclopentil)amino]metil]benzenometanol;

[0174] a-[[(3-Metilciclo-hexil)amino]metil]benzenometanol;

[0175] a-[[(3-Aminociclohexil)amino]metil]benzenometanol;

[0176] a-[[(4-Aminociclohexil)amino]metil]benzenometanol;

[0177] a-[[(3-Fluorociclobutil)amino]metil]benzenometanol;

[0178] a-[[(3-Metilciclobutil)amino]metil]-2-piridinametanol;

[0179] α-[[(3-Hidroxiciclobutil)amino]metil]-3piridinametanol;

[0180] (aR)-a-[[(3Fluorociclobutil)amino]metil]benzenometanol;

[0181] a-[[(4-Metilciclo-heptil)amino]metil]benzenometanol;

[0182] (aR)-a-[[(1-Metil-3Petição 870250102326, de 07 / 11 / 2025, pág. 31 / 101 24 / 93 azetidinil)amino]metil]benzenometanol;

[0183] a-[[(1-Metil-3azetidinil)amino]metil]benzenometanol;

[0184] (aS)-a-[[(1-Metil-3azetidinil)amino]metil]benzenometanol;

[0185] a-[[(4-Hidroxiciclohexil)amino]metil]benzenometanol;

[0186] α-[[(3-Metilciclopentil)amino]metil]-3piridinametanol;

[0187] α-[[(3-Metilciclopentil)amino]methyl]-4piridinametanol;

[0188] α-[[(3-Hidroxiciclobutil)amino]methyl]-2piridinnametanol;

[0189] α-[[(4-Metilciclo-hexil)amino]metil]-4piridinametanol;

[0190] α-[[(3-Metilciclo-hexil)amino]metil]-4piridinametanol;

[0191] (αR)-α-[[(1-Metil-3pirrolidinil)amino]methyl]benzenometanol;

[0192] ^^-[[(Ι-ΜθΙιΙ^pirrolidinil)amino]metil]benzenometanol;

[0193] α-[[(1-Metil-3pirrolidinil)amino]methyl]benzenometanol; 5-[(2-Hidroxi-2-feniletil)amino]ciclo-octanol;

[0195] α-[[(3-Fluorociclobutil)amino]metil]-3piridinametanol;

[0196] α-[[(1-Metil-3piperidinil)amino]metil]benzenometanol;

[0197] α-[[(1-Metil-3-azetidinil)amino]metil]-3piridinametanol; Petição 870250102326, de 07 / 11 / 2025, pág. 32 / 101 25 / 93

[0198] a-[[(Hexa-hidro-1-metil-1H-azepin-4il)amino]metil]benzenometanol;

[0199] α-[[(3-Fluorociclobutil)amino]metil]-2piridinametanol;

[0200] a-[[(1-Metil-3-pirrolidinil)amino]metil]-4piridinametanol;

[0201] a-[[(1-Metil-3-pirrolidinil)amino]metil]-3piridinametanol;

[0202] a-[[(1-Metil-3-azetidinil)amino]metil]-2piridinametanol;

[0203] (C)

[0204] α-[[(1^N-4piperidinil)amino]methyl]benzenometanol, 2-((1-benzylpiperidin-4-yl)amino)-1-phenylethanol,

[0206] 4-(1-hydroxy-2-((1-methylpiperidin-4-yl)amino)ethyl)phenol,

[0207] 4-(2-((1-benzylpiperidin-4-yl)amino)-1-hydroxyethyl)phenol,

[0208] 4-(2-((1-butylpiperidin-4-yl)amino)-1-hydroxyethyl)phenol,

[0209] 3-(2-((1-butylpiperidin-4-yl)amino)-1-hydroxyethyl)phenol,

[0210] 4-(1-hydroxy-2-((1-(2-methoxyethyl)piperidin-4yl)amino)ethyl)phenol, ou

[0211] 4-(1-hydroxy-2-((1-phenethylpiperidin-4-yl)amino)ethyl)phenol;

[0212] (D) Petition 870250102326, de 07 / 11 / 2025, p. 33 / 101 26 / 93 (Mon) Petition 870250102326, de 07 / 11 / 2025, p. 34 / 101 27 / 93

[0213] For the avoidance of doubt, the ring comprising Q1 to Q5 (also referred to here as ring Q) represents a phenyl group optionally substituted by one or more Y1 groups, or a 5- or 6-membered heteroaryl group optionally substituted by one or more Y2 groups.

[0214] Several heteroaryl groups are well known to specialists, such as pyridinyl, pyridonyl, pyrrolyl, furanyl, thiophenyl, oxadiazolyl, thiadiazolyl, thiazolyl, oxazolyl, pyrazolyl, triazolyl, tetrazolyl, isoxazolyl, isothiazolyl, imidazolyl and the like. Oxides of heteroaryl / heteroaromatic groups are also Petition 870250102326, dated 07 / 11 / 2025, p. 35 / 101 28 / 93 are included within the scope of the invention (e.g., N-oxide).

[0215] In certain embodiments, when representing a heteroaryl, the ring comprising Q1 to Q5, as defined in this document, may include one or more (for example, one or two, as one) heteroatoms, which may be selected from O, S and N (for example, from O and N, as N). For example, the ring Q, as defined in this document, may include a heteroatom, which may be selected from O, S and N (for example, O and N, as N).

[0216] In certain embodiments, when representing a heteroaryl, the ring comprising Q1 to Q5, as defined in this document, may be a 6-membered heteroaryl. Thus, the ring comprising Q1 to Q5 may represent phenyl optionally substituted by one or more (e.g., one) Y1, or a 5- or 6-membered heteroaryl optionally substituted by one or more (e.g., one) Y2.

[0217] More specific heteroaryl groups representing the ring comprising Q1 to Q5 which may include pyridinyl, such as pyridin3-yl (referring to the standard numbering in which the N atom represents position 1).

[0218] In certain embodiments, the ring comprising Q1 to Q5 may represent:

[0219] phenyl optionally replaced by one or more (e.g., one) Y1, or

[0220] pyridyl optionally replaced by one or more (e.g., one) Y2.

[0221] In more specific embodiments, the ring comprising Q1 to Q5 may represent:

[0222] phenyl optionally replaced by one or more (e.g., one) Y1, or

[0223] piridin-3-ila optionally replaced by one or more (e.g., one) Y2.

[0224] Thus, in certain forms, the compound Petition 870250102326, dated 07 / 11 / 2025, p. 36 / 101 29 / 93 of formula IX can be represented as a compound of formula IA or IB. J” N R1(Z)n NY / Z)(v^Pj·' (γ2)χ y γγ X^ S-rX N Srí _m2IAm2IB

[0225] where R1, Z, Y1, Y2, m1, m2 and en are defined for the compounds of formula IX (including all its embodiments), v represents 0 to 5 and w represents 0 to 4.

[0226] For the avoidance of doubt, the ring structure comprising Q1 to Q5, as provided in formulas IA and IB (and in other embodiments), may also be applied to formula I (including all its embodiments).

[0227] For the avoidance of doubt, the ring comprising Q1 to Q5 may be replaced by a number of Y1 or Y2 groups, as defined herein, as appropriate under the circumstances. The person skilled will understand that the (maximum) number and position of such substituents will be dictated by the nature of the ring, such as the ring size and level of saturation thereof. Furthermore, the person skilled will understand that such substituents may be present in suitable varieties comprised in ring Q, for example, suitable C (carbon) varieties.

[0228] In certain embodiments, the ring comprising Q1 to Q5 is replaced by up to two (i.e., 0 to 2) Y1 or Y2 groups, as appropriate.

[0229] In more specific embodiments, the ring comprising Q1 to Q5 is replaced by up to one (i.e., 0 or 1) group Y1 or Y2, as appropriate.

[0230] In more specific embodiments, the ring comprising Q1 to Q5 is (i.e., needs to be) replaced by a Y1 or Y2 group, as appropriate (i.e., in compounds of formula IA, v is 1 and, in compounds of formula IB, w is 1). Petition 870250102326, dated 07 / 11 / 2025, p. 37 / 101 30 / 93

[0231] In particular embodiments, taking the point of attachment to the essential moiety -CH(OH)- as position 1, at least one (or, when only one of these groups is present, the) Y1 or Y2 group, as appropriate, may be located at position 2 or 3 (which may also be called ortho and meta positions, respectively).

[0232] In certain embodiments, the ring comprising Q1 to Q5 may represent:

[0233] phenyl substituted by one or more (e.g., one) Y1, or

[0234] 6-membered heteroaryl replaced by one or more (e.g., one) Y2.

[0235] In more specific embodiments, the ring comprising Q1 to Q5 may represent:

[0236] phenyl substituted by one or more (e.g., one) Y1, or

[0237] piridilla (also called pyridinila) replaced by one or more (for example, one) Y2.

[0238] For example, the ring comprising Q1 to Q5 can represent:

[0239] phenyl replaced by a Y1 (for example, in position 2 or 3, using standard numbering) or

[0240] pyridin-3-yl replaced by a Y2 (for example, at position 5 using standard numbering, which may also be referred to as position 3 when the point of attachment to the essential moiety -CH(OH)- is considered to be position 1).

[0241] Thus, in certain embodiments, the compounds of formulas IA and IB can be represented as compounds of formulas IA' and IB', respectively. Petition 870250102326, dated 07 / 11 / 2025, p. 38 / 101 31 / 93 Y1aOH H R1 N _ (Z)n X m2 IA OH H? 1 (Z)n ^)m1 X m2 IB'

[0242] where R1, Z, Y2, n, ml and m2 are defined for compounds of formula IX (such as compounds of formulas IA and IB, including all their embodiments), and where one of Y1a and Y1b (in particular, Y1b) represents Y1 and the other represents H.

[0243] In certain embodiments, each Y1 independently represents Ra1, halo (e.g., F or Cl), -CN, -N(Rb1)Rc1 or -ORd1.

[0244] In certain embodiments, Ra1 represents C1-3 alkyl (such as linear or branched C1-3 alkyl, for example, linear C1-3 alkyl) optionally substituted by one or more halos.

[0245] In more specific embodiments, Ra1 represents C1 alkyl (i.e., methyl) optionally substituted with one or more halos. For example, Ra1 may represent -CH3 or -CF3.

[0246] In more specific embodiments, each Y1 independently represents halo (e.g., F or Cl) or -CN.

[0247] In more specific modalities, each Y1 independently represents Cl or F.

[0248] In more specific modalities, each Y1 independently represents F.

[0249] In other specific modalities, each Y1 independently represents -CN.

[0250] In certain modalities, one or more (for example, each) Y1 represents -ORd1. In other specific modalities, Rd1 represents H.

[0251] In certain embodiments, one or more (e.g., each) Y1 represents -NRb1Rc1. In other specific embodiments, Rb1 represents H. In other specific embodiments, Rc1 represents H or C1-4 alkyl, Petition 870250102326, dated 07 / 11 / 2025, page 39 / 101 32 / 93 as H.

[0252] In certain embodiments, each Y2 independently represents Ra2, halo (e.g., F or Cl), -CN, -N(Rb2)Rc2 or -ORd2.

[0253] In certain embodiments, Ra2 represents C1-3 alkyl (such as linear or branched C1-3 alkyl, for example, linear C1-3 alkyl) optionally substituted by one or more halos.

[0254] In more specific embodiments, Ra2 represents C1 alkyl (i.e., methyl) optionally substituted with one or more halos. For example, Ra1 may represent -CH3 or -CF3.

[0255] In more specific modalities, each Y2 represents Cl or F independently.

[0256] In more specific modalities, each Y2 represents F independently.

[0257] In certain modalities, Rd2 represents H.

[0258] In certain embodiments, Rb2 represents H and / or (e.g., and) Rc2 represents H or C1-4 alkyl, e.g., H.

[0259] For the avoidance of doubt, as indicated in this document, embodiments of the invention will include combinations of embodiments as described in this document.

[0260] In certain embodiments, each Y1 and Y2 independently represents Ra1, halo (e.g., F or Cl) or -CN.

[0261] For example, in certain modalities that can be mentioned:

[0262] each Y1 independently represents Ra1, halo (e.g., F or Cl) or -CN;

[0263] Ra1 represents C1-3 alkyl (such as linear or branched C1-3 alkyl, for example, linear C1-3 alkyl) optionally substituted with one or more halos;

[0264] each Y2 independently represents Ra2, halo (e.g., F or Cl) or -CN; and Petition 870250102326, dated 07 / 11 / 2025, p. 40 / 101 33 / 93

[0265] Ra2 represents C1-3 alkyl (such as linear or branched C1-3 alkyl, for example, linear C1-3 alkyl) optionally substituted with one or more halos.

[0266] In certain embodiments, each Y1 and Y2 represents Cl or F (particularly, F).

[0267] In certain forms, n represents at least 1 (i.e., there is a requirement that at least one group Z be present). In other forms, n represents up to 5, such as up to 4, up to 3, or up to 2.

[0268] In specific modalities:

[0269] where ring A represents a cycloalkyl group, n represents 1 to 5 (e.g., 1 to 3, as 1 or 2, e.g., 1); and

[0270] where ring A represents a heterocycloalkyl group, n represents 0 to 5 (e.g., 0 to 3, such as 0, 1 or 2, e.g., 1).

[0271] In other modalities:

[0272] where ring A represents a cycloalkyl group, n represents 1 to 3 (such as 1 or 2, for example, 1); and

[0273] where ring A represents a heterocycloalkyl group, n represents 1 to 3 (such as 1 or 2, for example, 1).

[0274] For example, in certain modalities, n represents 1 to 4, as well as 1 to 3.

[0275] In more specific modalities, n represents 1 or 2.

[0276] In other specific modalities, n represents 1.

[0277] In certain embodiments, R1 represents H or C1-4 alkyl (such as C1-2 alkyl, for example, methyl).

[0278] In certain embodiments, R1 represents H. In alternative embodiments, R1 represents methyl.

[0279] In certain modes, the sum of m1 and m2 is 1 or 2.

[0280] In other specific modalities, the sum of m1 Petition 870250102326, dated 07 / 11 / 2025, p. 41 / 101 34 / 93 and m2 is 2. They represent 1. (carbon).

[0281] In certain modalities, m1 and m2

[0282] In certain modalities, X represents C

[0283] In more specific embodiments, X represents C (carbon) and m1 and m2 represent 1. Thus, in such embodiments, ring A (for example, the ring comprising X) represents cyclohexyl.

[0284] Thus, in some embodiments, compounds of formula I may be present as a compound of formula IC OH Q2q3 Q1 Q5 Q5 Q4 Q IC

[0285] wherein R1, the ring comprising Q1a Q5, Z and en are as described in this document (i.e., as described in the first aspect of the invention, including all embodiments and particular features and their combinations).

[0286] In certain forms, X represents N (nitrogen).

[0287] In more specific embodiments, X represents N (nitrogen) and m1 and m2 represent 1. Thus, in such embodiments, ring A (for example, the ring comprising X) represents piperidin-4-yl.

[0288] Thus, in some embodiments, compounds of formula I may be present as a compound of formula ID Q2 Q3m OH hr1 Ql, N Q5Q5Q4Q NH (Z)n ID,

[0289] where R1, the ring comprising Q1a Q5, Z en are as described in this document (i.e., as described in the first Petition 870250102326, dated 07 / 11 / 2025, p. 42 / 101 35 / 93 aspect of the invention, including all embodiments and particular features and their combinations). For the avoidance of doubt, a Z group may be present on the N of the piperidine ring.

[0290] In certain embodiments (for example, formula IX, where n represents 1; and m1 and m2 represent 1), the Z group is present at position 3 or 4 of the ring comprising the X group (relative to the point of attachment to the essential nucleus of the compound).

[0291] Thus, in certain embodiments, the ring A can be represented as follows: < R1 Z1 Z2

[0292] where the wavy line indicates the point of connection with the essential core of the compound, and one of Z1 and Z2 represents Z and the other represents H.

[0293] For example, in certain embodiments that may be mentioned, Z2 represents Z and Z1 represents H. Thus, in certain embodiments, compounds of formula I may be compounds of formula IE. OH q2 Q3 Q1 aQ5q4

[0294] wherein R1, the ring comprising Q1 to Q5, Z and X are as described in this document (i.e., as described in the first aspect of the invention, including all embodiments and particular features and their combinations).

[0295] In certain embodiments, when present on a carbon atom, Z independently represents Ra3, -CN, -N3, -N(Rb3)Rc3, -ORd3, -S(O)pRe3, -S(O)qN(Rf3)Rg3, -N(Rh3)S(O)tRi3, or =O.

[0296] In more specific modalities, when present Petition 870250102326, dated 07 / 11 / 2025, p. 43 / 101 36 / 93 in a carbon atom, each Z independently represents Ra3, -CN, N(Rb3)RC3, -ORd3, -S(O)qN(Rf3)Rg3, -N(Rh3)S(O)tRi3, or =O.

[0297] In more specific modalities, when present on a carbon atom, each Z independently represents Ra3, -N(Rb3)Rc3, ORd3, -N(Rh3)S(O)tRi3, or =O.

[0298] In more specific embodiments, when present on a carbon atom, each Z independently represents Ra3, -N(Rb3)Rc3, ORd3, or -N(Rh3)S(O)tRi3, as Ra3.

[0299] In certain modalities, each t represents 2.

[0300] In certain embodiments, when representing a Z group present on a carbon atom, Ra3 represents C1-6 alkyl (e.g., C1-4 alkyl, such as C2 or C4 alkyl) optionally substituted by one or more (e.g., one or two, e.g., one) G1 groups.

[0301] For example, in some of these embodiments, Z2 represents Ra3, optionally replaced by one or more (e.g., one or two, as one) G1 groups, and Z1 represents H.

[0302] In some of these modalities, Gi represents N(Rb4)RC4 or -N(Rh4)S(O)rRi4.

[0303] In certain embodiments, Rb4 represents H and / or (for example, and) Rc4 represents C1-2 alkyl optionally substituted with one or more halos or =O, such as C2 alkyl optionally substituted with =O

[0304] In certain embodiments, Rh4 represents H and / or (e.g., and) Ri4 represents C1-2 alkyl, optionally replaced by one or more halos, such as C1 alkyl.

[0305] In certain modalities, r represents 2.

[0306] For example, in some of these embodiments, such as when a substituent in a Z group is present on a carbon atom, G1 represents -NH(O)Me or -NHS(O)2Me.

[0307] In certain embodiments, Rb3e / or (for example, or) Rc3 represents H. Petition 870250102326, dated 07 / 11 / 2025, page 44 / 101 37 / 93

[0308] In certain embodiments, Rb3 and / or (for example, or) Rc3 represents C1-6 alkyl optionally substituted by one or more groups selected from halo and G2. In such specific embodiments, G2 may represent Ra4 or =O.

[0309] In certain embodiments, Rd3 represents C1-6 alkyl (such as C1-2 alkyl, for example, methyl or ethyl), optionally substituted by one or more groups selected independently from halo and G2. In certain embodiments, G2 may represent Ra4, -OH or =O.

[0310] In certain modalities, Rh3 represents H.

[0311] In certain embodiments, Ri3 represents C1-6 alkyl (such as C1-2 alkyl, for example, methyl or ethyl) optionally substituted by one or more groups selected independently from halo and G2.

[0312] As described in this document, when present on a nitrogen atom, Z independently represents Ra3, S(O)pRe3, or -S(O)qN(Rf3)Rg3.

[0313] In certain embodiments, when present on a nitrogen atom, Z independently represents Ra3 or -S(O)pRe3.

[0314] In certain embodiments, when representing a Z group present on a nitrogen atom, Ra3 represents C1-6 alkyl (e.g., C1-4 alkyl, such as Ci or C2 alkyl) optionally substituted by one or more (e.g., one or two) G1 groups. For example, G1 may independently represent -ORd4 (such as -OMe or -OH), -N(Rb4)Rc4 (such as -NMe2) or =O.

[0315] For example, in some of these embodiments, Z2 represents Ra3, optionally replaced by one or more (e.g., one or two) G1 groups, and Z1 represents H.

[0316] In some of these modalities, G1 represents =O.

[0317] In certain embodiments, when representing a Z group present on a nitrogen atom, -S(O)pRe3 represents S(O)pRe3 where Re3 represents C1-4 alkyl, such as methyl. Petition 870250102326, dated 07 / 11 / 2025, page 45 / 101 38 / 93

[0318]

[0319] In certain modalities, p represents 2. For example, when present on a nitrogen atom, Z can independently represent -CH2C(O)OMe, -CH2C(O)OH, C(O)Me, -S(O)2CH2C(O)OMe, -S(O)2CH2C(O)OH, -S(O)2nBu or -S(O)2Me, as C(O)Me or -S(O)2Me.

[0320] For the avoidance of doubt, “when present on a carbon atom (or nitrogen atom, as the case may be)” refers to when Z is present on a carbon (or nitrogen atom, as the case may be) of ring A (including all its forms).

[0321] The expert will understand that the R1, X, m1, m2 groups, the Q ring and its substituents, and the Z groups (including any substituents) that may be mentioned include those present in the examples provided in this document.

[0322] The specific compounds of the first aspect of the invention that may be mentioned include the compounds of the examples provided in this document and their pharmaceutically acceptable salts.

[0323] As described herein, the compounds of the first aspect of the invention may also contain one or more asymmetric carbon atoms and therefore may exhibit optical isomerism and / or diastereoisomerism. Furthermore, some of these diastereoisomers and / or optical isomers have been found to be more useful in treating the conditions described in this document, for example, hyperglycemia or disorders characterized by hyperglycemia (such as type 2 diabetes).

[0324] Thus, the compound of formula I may be present as a compound of formula IF and IG (Z)n ^ml Xm2IG (Z)n ^)m1 Xm2IF Q2 Q2 Q Q

[0325] where R1, the ring comprising Q1 to Q5, Z, X, n, m1 and m2 are as described in this document (i.e., as described in Petition 870250102326, dated 07 / 11 / 2025, p. 46 / 101 39 / 93 first aspect of the invention, including all embodiments and particular features and their combinations).

[0326] In specific embodiments, the compound of formula I is a compound of formula IF.

[0327] To avoid doubt, the stereochemistry described in the compounds of formulas IF and IG can be applied to all forms of the compounds of formula I.

[0328] The expert will understand that, in addition to the carbon containing the essential hydroxyl group, the compounds of the invention may include other stereocenters. For the avoidance of doubt, unless specified, the stereochemistry in all stereocenters (including stereochemistry present in positions other than the carbon containing the essential hydroxyl group) may be in any configuration (i.e., in the R or S configuration), or may be present in compounds as a mixture thereof (e.g., a racemic mixture).

[0329] Thus, in a specific embodiment, the compound of formula IF may be a compound of formula IH or IJ. Q2z Q3vyQ5Q4Q OHH R1(Z)nV^Apmi ΎTCHm2IH Q2 Q3 Q1 ?HHRi Á N,( OQ5 Q4Q mi IJ

[0330] where R1, ring Q, Z, X, n, m1 and m2 are as described in this document (i.e., as described in the first aspect of the invention, including all embodiments and particular features and their combinations).

[0331] In other specific embodiments, where X represents C (carbon), the compound with formula IH is a compound with formula IK or a compound with formula IL, and the compound with formula IJ is a compound with formula IM or a compound with formula IN. Q2, Q3, ?HHRi Q1 A. .n Q4Q5 ZIK Q2z Q3t OH HRi Qi A. „N ^Q5 Q4Q )m1ZIL Petition 870250102326, dated 07 / 11 / 2025, p. 47 / 101 40 / 93 q2 Qm2 ZIM Q2 Qm2 ZZ IN

[0332] where R1, ring Q, Z, ml and m2 are as described in this document (i.e., as described in the first aspect of the invention, including all embodiments and particular features and their combinations).

[0333] In other specific embodiments, the compound of formula IF is a compound of formula IO or a compound of formula IP γΐα OH Ylb H R1(Z)n ^)m1 Xm2IO y2 OH (Z)n ^)m1 Xm2IP

[0334] where R1, Y1a, Y1b, Y2, Z, X, n, m1 and m2 are as described in this document (i.e., as described in the first aspect of the invention, including all particular embodiments and features and their combinations).

[0335] A person knowledgeable will understand that references to specific stereoisomers of a compound of formula I (for example, in the case of compounds of formula I, where the carbon substituted by the essential -OH group is in the R configuration) refer to the specific stereoisomer present in the substantial absence of the other (corresponding) stereoisomer(s) (for example, in the case of compounds of formula I, where the carbon substituted by the essential -OH group is in the opposite configuration, i.e., in the S configuration).

[0336] As used herein, references to the substantial absence of the corresponding opposite stereoisomer shall refer to the desired stereoisomer (e.g., in the case of compounds of formula I, where the carbon substituted by the essential group -OH is in the (R) configuration) being present with a purity of at least 80% (e.g., at least 90%, such as at least 95%) relative to the other (e.g., the opposite) stereoisomer (e.g., in the case of compounds of formula I, where the carbon substituted by the essential group Petition 870250102326, dated 07 / 11 / 2025, p. 48 / 101 41 / 93 OH is in the S configuration). Alternatively, in such cases, compounds may be indicated as being present in the substantial absence of the compound in the other configuration(s) (i.e., configuration (S)), which may indicate that the compound in the relevant configuration is present in an enantiomeric excess (ee), or when two or more stereogenic centers are defined, in a diastereomeric excess (de) of at least 80% (such as at least 90%, at least 95%, at least 98%, or particularly at least 99%, for example at least 99.9%).

[0337] In some embodiments, the compound in the relevant configuration is present in an enantiomeric excess (ee), or when two or more stereogenic centers are defined, in a diastereomeric excess (de), of at least 90% (such as at least 95%, at least 98% or, particularly, at least 99%, for example, at least 99.9%).

[0338] For the avoidance of doubt, when stereochemistry of more than one position is specified, the compound will be present in the substantial absence of all other diastereomers.

[0339] To avoid doubt, when the stereochemistry of a given position is not specified, the compounds of the invention will include compounds in which that position has any available stereochemical configuration and mixtures thereof (e.g., racemic mixtures). Thus, compounds referred to as having a specific stereochemistry at a defined position (e.g., in the case of compounds of formula I, the carbon substituted by the essential -OH group is in the R configuration) may also have stereochemistry at one or more positions and therefore may exist as mixtures of enantiomers or diastereomers with respect to the stereochemistry at those positions. MEDICAL USES

[0340] As indicated in this document, the compounds of the invention and, therefore, the compositions and kits containing them, are useful as pharmaceutical products.

[0341] Thus, according to a second aspect of the invention, a compound of the first aspect of the invention is provided, as follows Petition 870250102326, dated 07 / 11 / 2025, p. 49 / 101 42 / 93 defined above (i.e., a compound as defined in the first aspect of the invention, including all embodiments and particular characteristics thereof), for use in medicine (i.e., for use as a pharmaceutical product, which may be described as use as a medicine).

[0342] In a second aspect embodiment, the compound is as defined in the first aspect, but without the caveat (B).

[0343] The compounds described in this document are β2 adrenergic receptor agonists and therefore suitable for the treatment of diseases such as those described in this document. This activity can be observed in the compounds of the invention by identifying compounds that stimulate glucose uptake in skeletal muscle cells, whose activity can be confirmed as being mediated by β2 receptor activation by observing that this activity is prevented or diminished in the presence of a β2 adrenergic receptor antagonist (e.g., selective) (as in the biological example provided in this document).

[0344] Thus, in a third aspect of the invention, a compound of the first aspect of the invention, as defined above, is provided for use in the treatment of a disease or disorder whose treatment is mediated by the activation of the β2 adrenergic receptor.

[0345] In a third alternative aspect of the invention, the use of a compound from the first aspect of the invention in the manufacture of a medicament for use in the treatment of a disease or disorder whose treatment is mediated by the activation of the β2 adrenergic receptor is provided.

[0346] In a third alternative aspect of the invention, a method is provided for treating a disease or disorder whose treatment is mediated by activation of the β2 adrenergic receptor, comprising administering a therapeutically effective amount of a compound from the first aspect of the invention to a patient in need thereof.

[0347] For the avoidance of doubt, references to compounds as defined in the first aspect of the invention shall include references to compounds Petition 870250102326, dated 07 / 11 / 2025, p. 50 / 101 43 / 93 of formula I (including all its forms) and its pharmaceutically acceptable salts.

[0348] In a third aspect embodiment, the compound is as defined in the first aspect, but without the caveats (B) to (M).

[0349] As indicated in this document, the compounds of the invention act by inducing glucose uptake in skeletal muscle cells, thereby allowing the reduction of blood glucose levels in vivo. Thus, the compounds of the invention may be specifically used in the treatment of hyperglycemia or a disorder characterized by hyperglycemia.

[0350] In a specific embodiment of the third aspect of the invention, a compound of the first aspect of the invention, as defined above, is provided for use in the treatment of hyperglycemia or a disorder characterized by hyperglycemia.

[0351] In an alternative embodiment of the third aspect of the invention, the use of a compound from the first aspect of the invention in the manufacture of a medicament for use in the treatment of hyperglycemia or a disorder characterized by hyperglycemia is provided.

[0352] In another alternative embodiment of the third aspect of the invention, a method is provided for treating hyperglycemia or a disorder characterized by hyperglycemia comprising administering to a patient in need a therapeutically effective amount of a compound from the first aspect of the invention.

[0353] For the avoidance of doubt, the term “hyperglycemia,” as used in this document, will be understood by those skilled in the art to mean a condition in which an excessive amount of glucose circulates in the blood plasma of the individual exhibiting it. In particular, it may refer to an individual (e.g., a human individual) with blood glucose levels exceeding approximately 10.0 mmol / L (e.g., exceeding approximately 11.1 mmol / L, e.g., exceeding approximately 15 mmol / L), although it may also refer to an individual (e.g., a human individual) with blood glucose levels exceeding Petition 870250102326, dated 07 / 11 / 2025, p. 51 / 101 44 / 93 approximately 7 mmol / L for a long period of time (e.g., for more than 24 hours, e.g., for more than 48 hours).

[0354] The specialist will understand that references to the treatment of a specific condition (or, similarly, to the treatment of that condition) take on their normal meanings in the field of medicine. In particular, the terms may refer to achieving a reduction in the severity of one or more clinical symptoms associated with the condition. For example, in the case of type 2 diabetes, the term may refer to achieving a reduction in blood glucose levels.In specific modalities, in the case of treatment of hyperglycemia or conditions characterized by hyperglycemia, the term may refer to achieving a reduction in blood glucose levels (e.g., to or below approximately 10.0 mmol / mL (e.g., to levels in the range of approximately 4.0 mmol / L to approximately 10.0 mmol / L), as well as to or below approximately 7.5 mmol / mL (e.g., to levels in the range of approximately 4.0 mmol / L to approximately 7.5 mmol / L) or to or below approximately 6 mmol / mL (e.g., to levels in the range of approximately 4.0 mmol / L to approximately 6.0 mmol / L)).

[0355] As used herein, references to patients will refer to a living subject being treated, including mammalian patients (e.g., human beings). Thus, in particular embodiments of the first aspect of the invention, the treatment is on a mammal (e.g., a human).

[0356] As used herein, the term therapeutically effective amount will refer to an amount of a compound that confers a therapeutic effect on the treated patient. The effect may be objective (i.e., measurable by some test or marker) or subjective (i.e., the subject gives an indication of and / or feels an effect).

[0357] Although the compounds of the first aspect of the invention may possess pharmacological activity as such, certain pharmaceutically acceptable (e.g., “protected”) derivatives of the compounds of the invention may exist or be prepared which may not possess such activity but may be administered parenterally or orally and subsequently metabolized. Petition 870250102326, dated 07 / 11 / 2025, page 52 / 101 45 / 93 in the body to form compounds of the invention. These compounds (which may have some pharmacological activity, provided that this activity is considerably less than that of the active compounds to which they are metabolized) can therefore be described as “prodrugs” of the compounds of the invention.

[0358] As used in this document, references to prodrugs will include compounds that form a compound of the invention, in an experimentally detectable amount, within a predetermined time, after enteral or parenteral administration (e.g., oral or parenteral administration). All prodrugs of the compounds of the first aspect of the invention are included in the scope of the invention.

[0359] For the avoidance of doubt, the compounds of the first aspect of the invention are useful because they possess pharmacological activity and / or are metabolized in the body after oral or parenteral administration to form compounds that possess pharmacological activity. In particular, as described in this document, the compounds of the first aspect of the invention are useful in the treatment of hyperglycemia or disorders characterized by hyperglycemia (such as type 2 diabetes), terms that will be readily understood by someone skilled in the art (as described in this document).

[0360] In one specific modality, the treatment is for a disorder (which may also be called a condition or disease) characterized by hyperglycemia.

[0361] In certain embodiments of the first aspect of the invention, the disorder is type 2 diabetes, such as type 2 diabetes of a subtype selected from the list consisting of maturity-onset diabetes in young people (MODY), adult-onset ketosis-prone diabetes, latent autoimmune diabetes in adults (LADA), and gestational diabetes.

[0362] In other forms, the disorder is type 1 diabetes, particularly when treatment also includes treatment with insulin (or a derivative and / or functional mimetic thereof).

[0363] In certain embodiments, the compounds of Petition 870250102326, dated 07 / 11 / 2025, p. 53 / 101 46 / 93 invention (i.e., the compounds of formula I, including all embodiments thereof) are for use in the treatment of type 2 diabetes (or useful in the manufacture of a medicament for such treatment, or useful in a method for such treatment, as described herein).

[0364] In other specific modalities, type 2 diabetes treatment is performed on a non-obese patient.

[0365] To avoid any doubt, those skilled in the art will understand that patients with a Body Mass Index (BMI) greater than 30 are considered obese.

[0366] In specific modalities, treatment may be for hyperglycemia in a patient at risk of developing type 2 diabetes, a condition that may be defined as prediabetes. Thus, the compounds of the invention may be useful in the prevention of type 2 diabetes (for example, in a patient with prediabetes).

[0367] As used in this document, the term prevention (and similarly, to prevent) includes references to the prophylaxis of the disease or disorder (and vice versa). In this way, references to prevention can also be references to prophylaxis, and vice versa. In particular, the term can refer to achieving a reduction in the probability of the patient (or healthy subject) developing the condition (e.g., at least a 10% reduction, such as at least a 20%, 30% or 40% reduction, e.g., at least a 50% reduction).

[0368] In other specific forms, type 2 diabetes is characterized by the patient having severe insulin resistance (SIR).

[0369] In other modalities, the treatment may be for hyperglycemia in a patient with type 1 diabetes. Thus, the compounds of the invention may be useful in the treatment of hyperglycemia in type 1 diabetes.

[0370] Those skilled in the art will understand that the compounds of the invention may be useful in the treatment of hyperglycemia in patients with impaired insulin production, such as in patients with cystic fibrosis. Thus, in Petition 870250102326, dated 07 / 11 / 2025, page 54 / 101 47 / 93 other modalities, the disorder characterized by hyperglycemia is cystic fibrosis-related diabetes.

[0371] In certain modalities that may be mentioned, the disorder characterized by hyperglycemia is (or is characterized by) severe insulin resistance (SIR), which may be understood by those familiar with the technique as referring to disorders in which the individual has normal or, in some cases, increased insulin production, but significantly reduced insulin sensitivity. In specific cases, these patients may not be obese (i.e., have a healthy weight). Thus, in certain modalities, these treatments are performed on patients who are not defined as obese (i.e., on patients who are defined as having a healthy weight).

[0372] For example, SIR can be identified in a patient based on the fact that the patient has fasting insulin >150 pmol / L and / or a glucose tolerance test insulin spike of >1,500 pmol / L, especially in individuals with a BMI < 30 kg / m2 (who may have normal glucose tolerance).

[0373] More specifically, SIR can be characterized by the fact that the patient does not have a significant response to the presence of insulin, which may result from a defect (e.g., a genetic defect) in insulin receptor function.

[0374] Specific disorders that can be characterized by SIR include: Rabson-Mendenhall syndrome, Donohue syndrome (leprechaunism), Type A and Type B insulin resistance syndromes, HAIR-AN syndromes (hyperandrogenism, insulin resistance and acanthosis nigricans), pseudoacromegaly and lipodystrophy.

[0375] Other specific disorders that can be characterized by SIR include Donohue syndrome and type A insulin resistance syndrome and, even more particularly, Rabson-Mendenhall syndrome.

[0376] Those versed in the technique will understand that the treatment Petition 870250102326, dated 07 / 11 / 2025, page 55 / 101 48 / 93 with compounds of the first aspect of the invention may include (i.e., be combined with) other treatments (i.e., additional / other) for the same condition. In particular, treatment with the compounds of the invention may be combined with other means for the treatment of type 2 diabetes, such as treatment with one or more therapeutic agents useful in the treatment of type 2 diabetes, as known to those skilled in the art, such as therapies requiring the patient to undergo a change in diet and / or exercise regimens and / or surgical procedures intended to promote weight loss (such as gastric banding surgery).

[0377] In particular, treatment with compounds of the invention may be carried out in combination with (for example, in a patient who is also being treated with) one or more (for example, one) additional compounds (i.e., therapeutic agents) that:

[0378] (i) are able to reduce blood sugar levels; and / or

[0379] (ii) are insulin sensitizers; and / or

[0380] (iii) increases insulin release,

[0381] all of which are described below.

[0382] In other embodiments, the compounds of the first aspect of the invention (i.e., the compounds of the invention) may be useful in the treatment of non-alcoholic fatty liver disease (NAFLD).

[0383] Non-alcoholic fatty liver disease (NAFLD) is defined by the excessive accumulation of fat in the form of triglycerides (steatosis) in the liver (designated as an accumulation of more than 5% of hepatocytes histologically). It is the most common liver disorder in developed countries (e.g., it affects about 30% of adults in the US) and most patients are asymptomatic. If left untreated, the condition can progressively worsen and eventually lead to liver cirrhosis. NAFLD is particularly prevalent in obese patients, with about 80% of patients considered to have the disease.

[0384] A subgroup of patients with NAFLD (e.g., between 2 and 5% of North American adults) presents with injury and inflammation. Petition 870250102326, dated 07 / 11 / 2025, page 56 / 101 49 / 93 of liver cells, in addition to excessive fat accumulation. This condition, called non-alcoholic steatohepatitis (NASH), is virtually indistinguishable histologically from alcoholic steatohepatitis. Although the simple steatosis observed in NAFLD does not directly correlate with increased morbidity or mortality in the short term, the progression of this condition to NASH dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. In fact, NASH is now considered one of the leading causes of cirrhosis (including cryptogenic cirrhosis) in the developed world.

[0385] The exact cause of NASH has not yet been elucidated, and it is almost certain that it is not the same in all patients. It is most closely related to insulin resistance, obesity, and metabolic syndrome (which includes diseases related to type 2 diabetes mellitus, insulin resistance, central (truncated) obesity, hyperlipidemia, low high-density lipoprotein (HDL) cholesterol, hypertriglyceridemia, and hypertension). However, not all patients with these conditions have NASH, and not all patients with NASH suffer from one of these conditions. Nevertheless, since NASH is a potentially fatal disease that leads to cirrhosis, liver failure, and hepatocellular carcinoma, there is a clear need for effective treatment.

[0386] In particular embodiments, the compounds of the invention (i.e., compounds of formula I, including all embodiments thereof) are for use in the treatment of non-alcoholic fatty liver disease (or useful in the manufacture of a medicament for such treatment, or useful in a method for such treatment, as described herein).

[0387] The process by which triglyceride fat accumulates in liver cells is called steatosis (i.e., hepatic steatosis). A person versed in the subject will understand that the term “steatosis” encompasses the abnormal retention of fat (i.e., lipids) in a cell. Thus, in certain embodiments of the first aspect of the invention, the treatment or prevention is of a fatty liver disease characterized by steatosis.

[0388] During steatosis, excess lipids Petition 870250102326, dated 07 / 11 / 2025, p. 57 / 101 50 / 93 fat accumulates in vesicles that displace the cell's cytoplasm. Over time, the vesicles can become large enough to distort the nucleus, and the condition is known as macrovesicular steatosis. Otherwise, the condition may be called microvesicular steatosis. Steatosis is practically harmless in mild cases; however, large accumulations of fat in the liver can cause significant health problems. Risk factors associated with steatosis include diabetes mellitus, protein malnutrition, hypertension, obesity, anoxia, sleep apnea, and the presence of toxins in the cell.

[0389] As described in this document, fatty liver disease is most commonly associated with alcohol or a metabolic syndrome (e.g., diabetes, hypertension, obesity, or dyslipidemia). Therefore, depending on the underlying cause, fatty liver disease may be diagnosed as alcohol-related fatty liver disease or non-alcoholic fatty liver disease (NAFLD).

[0390] Specific diseases or conditions associated with fatty liver disease that are not related to alcohol include metabolic conditions such as diabetes, hypertension, obesity, dyslipidemia, abetalipoproteinemia, glycogen storage diseases, Weber-Christian disease, acute fatty liver of pregnancy, and lipodystrophy. Other non-alcohol-related factors associated with fatty liver disease include malnutrition, total parenteral nutrition, severe weight loss, refeeding syndrome, jejunoileal bypass, gastric bypass, polycystic ovary syndrome, and diverticulosis.

[0391] The compounds of the invention have been considered particularly useful in the treatment or prevention of NAFLD, which may be referred to as non-alcohol-related fatty liver disease. A “non-alcohol-related” fatty liver disease can be diagnosed when the patient’s alcohol consumption is not considered the primary causal factor. A typical threshold for diagnosing a fatty liver disease as “non-alcohol-related” is a daily consumption of less than 20 g for women and less than 30 g for men. Petition 870250102326, dated 07 / 11 / 2025, p. 58 / 101 51 / 93 men.

[0392] If left untreated, individuals suffering from fatty liver disease may begin to exhibit liver inflammation (hepatitis). It has been postulated that one of the possible causes of this inflammation may be lipid peroxidation damage to the membranes of liver cells. Inflammation of a fatty liver can lead to several serious diseases, and therefore it is desirable to treat or prevent fatty liver disease before inflammation occurs. Thus, in certain embodiments of the first aspect of the invention, the treatment or prevention is of an inflammation-associated NAFLD.

[0393] Non-alcoholic steatohepatitis (NASH) is the most aggressive form of NAFLD and is a condition in which excessive fat accumulation (steatosis) is accompanied by liver inflammation. When advanced, NASH can lead to the development of scar tissue in the liver (fibrosis) and eventually to cirrhosis. As described above, the compounds of the invention have been found useful in the treatment or prevention of NAFLD, particularly when accompanied by liver inflammation. Therefore, the compounds of the invention are also useful in the treatment or prevention of NASH. Thus, in another embodiment of the first aspect of the invention, the treatment or prevention is of non-alcoholic steatohepatitis (NASH).

[0394] Those skilled in the art will understand that treatment with compounds of the first aspect of the invention may include (i.e., be combined with) other (i.e., additional / other) treatments for the same condition. In particular, treatment with compounds of the invention may be combined with other means for the treatment of a fatty liver disease, as described herein, such as treatment with one or more other therapeutic agents that are useful in the treatment of a fatty liver disease, as known to those skilled in the art; for example, therapies comprising requiring the patient to undergo a change in diet and / or perform exercise regimens and / or surgical procedures designed to promote weight loss (such as gastric banding surgery). Petition 870250102326, dated 07 / 11 / 2025, page 59 / 101 52 / 93

[0395] In particular, treatment with the compounds of the invention can be carried out in combination with (for example, in a patient who is also being treated with) one or more (for example, one) additional compounds (i.e., therapeutic agents) that are capable of reducing the level of fat (for example, triglycerides) in the liver.

[0396] References to the treatment of fatty liver disease may refer to achieving a therapeutically significant reduction in fat (e.g., triglyceride levels) in liver cells (such as a reduction of at least 5% in weight, for example, a reduction of at least 10%, or at least 20%, or even 25%).

[0397] As described in this document, the compounds of the invention may be useful in the treatment of a disease or disorder whose treatment is mediated by the activation of the β2 adrenergic receptor.

[0398] In certain embodiments, the compounds of the first aspect of the invention may be understood as positive modulators of the β2 adrenergic receptor, which may be referred to as β2 adrenergic receptor agonists.

[0399] The specialist will understand what “β2 adrenergic receptor” (or “β-AR”) means. These receptors are known in the art and have been reviewed, for example, in Johnson, M., J. Allergy Clin. Immunol., 117, 18-24 (2006). To avoid confusion, adrenergic receptors are a class of G protein-coupled receptors that bind to and are activated by their endogenous ligands, the catecholamines, adrenaline and noradrenaline. The adrenergic receptor is divided into five types: αι, α2, βι, β2, and β3. These subtypes are expressed in distinct patterns and are involved in different physiological processes, so ligands that can selectively target a subtype have therapeutic potential for various diseases. The present invention relates to the β2 adrenergic receptor, although the compounds may interact with one or more adrenergic receptors (e.g., one or more β adrenergic receptors).

[0400] The term “positively modulates the activity of Petition 870250102326, dated 07 / 11 / 2025, pp. 60 / 101 The term "53 / 93 e2-adrenergic receptor" will be understood to mean that the compound is capable of altering receptor signaling.

[0401] As used in this document, the term “β2 agonist” means β2 adrenergic receptor agonist. In certain embodiments, the term β2 agonist is understood to include compounds that are primarily β2 agonists but may also exhibit some agonism for other adrenergic receptors. In this application, the terms “β2 adrenergic receptor agonist”, “β2 AR agonist”, “^AR agonist”, and “β2 agonist” may be used interchangeably.

[0402] Thus, in certain modalities, references to β2 agonists may include both selective and non-selective agonists.

[0403] In certain embodiments, references to β2 agonists may include any ligand that alters receptor signaling, including, but not limited to, full and partial agonists. Furthermore, the β2 agonists that may be used in accordance with various aspects and embodiments of the present disclosure may be short-acting, long-acting, or ultra-long-acting.

[0404] As used in this document, the term “mediated by β2 adrenergic receptor activation” is used to indicate that activation of the receptor regulates or causes a physiological response that, in turn, will provide a biological effect corresponding to (or leading to) the treatment of the disease or disorder.

[0405] As used in this document, references to diseases and disorders whose treatment is “mediated by β2 adrenergic receptor activation” may also refer to diseases and disorders (and, in particular, their treatment) that are, among others, “associated”, “mediated”, “affected”, “regulated”, “modulated” and “linked” to the β2 adrenergic receptor.

[0406] As described in this document, diseases and disorders whose treatment is mediated by the activation of the β2 adrenergic receptor are known to experts in the art. Thus, the expert will understand that, in Petition 870250102326, dated 07 / 11 / 2025, pp. 61 / 101 54 / 93 with regard to some of the diseases and disorders described in this document, the suitability of the compounds of the invention for the treatment of such diseases and disorders may be known to experts in the field; for example, based on the disclosures mentioned below (the content of which is incorporated herein by reference).

[0407] In addition to those described above, specific diseases and disorders whose treatment is mediated by the activation of the β2 adrenergic receptor that may be mentioned include:

[0408] neurodegenerative diseases, such as MCI (mild cognitive impairment), aMCI (amnestic MCI), vascular dementia, mixed dementia, FTD (frontotemporal dementia), HD (Huntington's disease), Rett syndrome, PSP (progressive supranuclear palsy), CBD (corticobasal degeneration), SCA (spinocerebellar ataxia), MSA (multiple system atrophy), SDS (Shy-Drager syndrome), olivopontocerebellar atrophy, TBI (traumatic brain injury), CTE (chronic traumatic encephalopathy), stroke, EKS (Wernicke-Korsakoff syndrome), normal pressure hydrocephalus, hypersomnia (narcolepsy), ASD (autism spectrum disorders), FXS (fragile X syndrome), YSC (tubular sclerosis complex), prion-related disorders, CJD (Creutzfeldt-Jakob disease), depressive disorders, CLD (Lewy body dementia), PD (Parkinson's disease), PD-D (PD dementia), ADHD (attention deficit hyperactivity disorder (ADHD)), Alzheimer's disease (AD),Early AD and DS (Down syndrome);

[0409] muscular dystrophy or a disorder characterized by muscular dystrophy, such as muscle injury, loss of muscle mass, muscle atrophy, muscle degeneration or sclerosis;

[0410] kidney disease, such as CKD (chronic kidney disease), ESRD (end-stage renal disease) and diabetic nephropathy;

[0411] inflammation or a disorder characterized by inflammation, such as sepsis, psoriasis, dermatitis, psoriasis-like cutaneous dermatitis, lacerations or HDF (human dermal fibroblasts), including localized acute inflammation, such as that related to endotoxemia and acute lung injury (ALI), Petition 870250102326, dated 07 / 11 / 2025, pp. 62 / 101 55 / 93 and respiratory conditions associated with inflammation, such as asthma and other lung disorders, such as chronic obstructive pulmonary disease (COPD); and

[0412] an autoimmune disease, such as SLE (systemic lupus erythematosus), RA (rheumatoid arthritis), MG (myasthenia gravis), MS and GD (Grave's disease).

[0413] The suitability of β2 adrenergic receptor agonists for the treatment of such conditions can be demonstrated by the data provided in this document and by reference to the literature known to those skilled in the art, such as that described in this document (the entire content of which, in particular the experimental results presented, will be understood to be incorporated herein by reference).

[0414] In particular, the suitability of β2 adrenergic receptor agonists for the treatment of some of the diseases and disorders mentioned here can be identified and, in some cases, confirmed by the disclosures in documents WO 2020 / 198466 A1 and WO 2021 / 003161 A1 (which, for the avoidance of doubt, are incorporated into this document by reference, in particular the examples provided).

[0415] In a specific embodiment, a compound of the first aspect of the invention, as defined above, is provided for use in the treatment of neurodegenerative diseases.

[0416] In certain modalities, the neurodegenerative disease is selected from MCI (mild cognitive impairment), aMCI (amnestic MCI), vascular dementia, mixed dementia, FTD (frontotemporal dementia), HD (Huntington's disease), Rett syndrome, PSP (progressive supranuclear palsy), CBD (corticobasal degeneration), SCA (spinocerebellar ataxia), MSA (multiple system atrophy), SDS (ShyDrager syndrome), olivopontocerebellar atrophy, TBI (traumatic brain injury), CTE (chronic traumatic encephalopathy), stroke, EKS (Wernicke-Korsakoff syndrome), normal pressure hydrocephalus, hypersomnia (narcolepsy), ASD (autism spectrum disorders), FXS (fragile X syndrome), YSC (hypersomnia complex) Petition 870250102326, dated 07 / 11 / 2025, page 63 / 101 56 / 93 tubular sclerosis), prion-related disorders, CJD (Creutzfeldt-Jakob disease), depressive disorders, DLC (Lewy body dementia), PD (Parkinson's disease), PDD (PD dementia), ADHD (attention deficit hyperactivity disorder), Alzheimer's disease (AD), early AD, and DS (Down syndrome).

[0417] Mittal. S., et al., Science., 357(6354), 891-898 (2017) describes that β2-adrenergic receptor agonists promote dopamine neuron health by reducing SNCA expression through deacetylation of H2K27 and mitochondrial free radicals. This may benefit nigral dopaminergic neurons, which are prone to mitochondrial bioenergetic dysfunction in the early stages of Lewy body neuropathy. β2-adrenergic receptor agonists are expressed in the substantia nigra and cortex, regions that are progressively affected by Parkinson's disease (PD). Therefore, β2-adrenergic receptor agonists may be used to reduce the risk and effect of PD.

[0418] Hishida. R., The Lancet, 870 (1992) describes that β2-adrenergic receptor agonists can beneficially affect wasting in patients with Parkinson's disease on prolonged levodopa use.

[0419] Uc, EY, et al., Clin. Neuropharmacol., 26(4), 207212 (2003) describes that the β2-adrenergic receptor agonist, albuterol, benefited patients with PD through two mechanisms, a greater response to levodopa and an increase in muscle mass.

[0420] O'Neill, et al., Br. J. Pharmacol., 177, 282-297 (2019) describes that β2-adrenergic receptor agonists restrict microglial activation and protect against the onset and progression of neuronal dopamine cell loss and related motor deficits caused by central or systemic inflammation. Therefore, targeting β2-adrenergic receptors with a β2-adrenergic receptor agonist provides an intervening prophylactic mechanism to protect against the progression of neurodegeneration and the exacerbated decline in motor function associated with systemic and central inflammation. As a result, β2-adrenergic receptor agonists may be beneficial in the treatment of PD-related neuropathy and inflammation-induced motor deficits. Petition 870250102326, dated 07 / 11 / 2025, p. 64 / 101 57 / 93

[0421] In other embodiments, a compound of the first aspect of the invention, as defined above, is provided for use in the treatment of muscular dystrophy or a disorder characterized by muscular dystrophy.

[0422] In such specific forms, muscular dystrophy is muscle damage, loss of muscle mass, muscle atrophy, muscle degeneration or sclerosis.

[0423] Jiang, G., et al., ISRN Pharma., 2011, 1-7 (2011) describes that β2-AR agonists improve weight loss in animals in models of denervation, amyotrophic lateral sclerosis, muscular dystrophy, disuse, aging, and myocardial discharge. Furthermore, in patients with immobilization conditions or muscular dystrophy, β2-AR agonists increase lean mass and improve skeletal muscle function. Additionally, β2-AR agonists have been found to promote myocardial recovery in patients with myocardial discharge atrophy resulting from the application of a left ventricular assist device.

[0424] Bartus, RT, et al., Neurobiol. Dis., 85, 11-24, 2016 indicates that β2-adrenergic receptor agonists can increase muscle volume and strength in patients with amyotrophic lateral sclerosis (ALS) by increasing neurotrophic factors.

[0425] In alternative embodiments, a compound of the first aspect of the invention, as defined above, is provided for use in the treatment of kidney disease.

[0426] In certain modalities, kidney disease is selected from CKD (chronic kidney disease), ESRD (end-stage renal disease), and diabetic nephropathy.

[0427] Cleveland, K., et al., FASEB Journal, 33(1), 514 (2019) describes that β2-adrenergic receptor agonists have been shown to induce mitochondrial biogenesis (MB) and promote recovery from acute kidney injury, and may be used as a possible therapy for diabetic nephropathy (DN). Petition 870250102326, dated 07 / 11 / 2025, pages 65 / 101 58 / 93

[0428] Jesinkey, SR, et al., J. Am. Soc. Nephrol., 25, 1157-1162 (2014) describes the need for mitochondrial biogenesis as an adaptive response to meet the increased metabolic and energy demands during organ recovery after acute injury. In particular, renal mitochondrial dysfunction has been associated with the pathogenesis of acute kidney injury (AKI), a disorder characterized by a rapid decrease in the excretory function of the kidneys and subsequent retention of harmful waste products.

[0429] In other embodiments, a compound of the first aspect of the invention, as defined above, is provided for use in the treatment of inflammation or a disorder characterized by inflammation.

[0430] In certain modalities, inflammation is (or is characterized by) sepsis, psoriasis, dermatitis, psoriasis-like cutaneous dermatitis, lacerations, or HDF (human dermal fibroblasts).

[0431] As an experienced person knows, inflammation is a tightly controlled process that ensures the proper location of immune cells, the release of pro- and anti-inflammatory mediators, the elimination of dead cells, and the containment of the pathogen.

[0432] The specialist knows that inflammation can also be a cause of respiratory diseases, such as asthma and other lung disorders, such as chronic obstructive pulmonary disease (COPD).

[0433] Grailer, JJ et al, J Innate Immun, 6, 607-618 (2014) shows that β2 adrenergic receptor blockade reduced survival and increased injury in mouse models of endotoxemia and LPS-induced acute lung injury, respectively. These results demonstrate the suitability of β2AR activation in the treatment of localized acute inflammation, such as that related to endotoxemia and acute lung injury.

[0434] Agac, D., et al., Brain, Behaviour and Immunity, 74, 176-185 (2018) describes that there is a unique synergistic pathway that converts acute inflammatory signals into an anti-inflammatory response and likely explains a variety of phenomena known to be involved in suppression. Petition 870250102326, dated 07 / 11 / 2025, pp. 66 / 101 59 / 93 immune response mediated by β2-adrenergic receptor agonists. In particular, β2-adrenergic receptor agonist signaling directly controls the expression of the anti-inflammatory cytokine IL-10. These results suggest the use of β2AR agonists in the treatment of inflammatory disorders such as sepsis.

[0435] Liu, F., et al., Cells, 511(9), 1-17 (2020) describes that β2-adrenergic receptor agonists have demonstrated significant antipsoriasis effects, which may involve the regulation of Th17 / Tregs axis balances and glycerophospholipid metabolism in response to imiquimod (IMQ)-induced psoriasis.

[0436] Provost, GS, et al., J. Investig. Dermatol., 135, 279-288 (2015) describes that β2-adrenergic receptor agonists reduce the differentiation of human dermal fibroblasts (HDF), thus reducing scar formation in a patient after a laceration or open wound.

[0437] In alternative embodiments, a compound of the first aspect of the invention, as defined above, is provided for use in the treatment of an autoimmune disease.

[0438] In certain modalities, the autoimmune disease is selected from SLE (systemic lupus erythematosus), RA (rheumatoid arthritis), MG (myasthenia gravis), MS and GD (Grave's disease).

[0439] Wu, et al., Front. Pharmacol., 1313(9), 1-9 (2018) describes that β2-adrenergic receptor agonists may be a treatment target for autoimmune diseases (AD), such as SLE (systemic lupus erythematosus), RA (rheumatoid arthritis), MG (myasthenia gravis), MS and GD (Grave's disease). PHARMACEUTICAL COMPOSITIONS

[0440] As described in this document, the compounds of the first, and therefore the second and third aspects of the invention are useful as pharmaceutical products. These compounds can be administered alone or through known pharmaceutical compositions / formulations.

[0441] In a fourth aspect of the invention, a pharmaceutical composition is provided comprising a compound as defined in Petition 870250102326, dated 07 / 11 / 2025, page 67 / 101 60 / 93 second or third aspect of the invention, and, optionally, one or more pharmaceutically acceptable adjuvants, diluents and / or carriers.

[0442] Those skilled in the art will understand that references herein made to compounds of the first aspect of the invention intended for specific uses (and, likewise, to uses and methods of use relating to the compounds of the invention) may also apply to pharmaceutical compositions comprising the compounds of the invention, as described in this document.

[0443] In a fifth aspect of the invention, a pharmaceutical composition is provided for use in the treatment of hyperglycemia or a disorder characterized by hyperglycemia (as defined herein as type 2 diabetes) comprising a compound as defined in the first aspect of the invention, and optionally one or more pharmaceutically acceptable adjuvants, diluents and / or carriers.

[0444] In a fifth alternative aspect of the invention, it relates to a pharmaceutical composition for use in the treatment or prevention of non-alcoholic fatty liver disease, as defined in this document.

[0445] In a fifth alternative aspect of the invention, it relates to a pharmaceutical composition for use in the treatment or prevention of non-alcoholic fatty liver disease, as defined in this document.

[0446] A person skilled in the art will understand that the compounds of the first (and therefore of the second and third) aspect of the invention can act systemically and / or locally (i.e., at a specific location).

[0447] A person skilled in the art will understand that the compounds and compositions described in the first to fifth aspects of the invention will normally be administered orally, intravenously, subcutaneously, buccally, rectally, dermally, nasally, tracheally, bronchially, sublingually, intranasally, topically, by any other parenteral route or by inhalation, in a pharmaceutically acceptable dosage form. The pharmaceutical compositions described herein will include compositions in the form of tablets, capsules or elixirs for oral administration, suppositories for rectal administration, sterile solutions or suspensions for parenteral administration. Petition 870250102326, dated 07 / 11 / 2025, pages 68 / 101 61 / 93 or intramuscular and similar. Alternatively, especially when these compounds of the invention act locally, the pharmaceutical compositions may be formulated for topical administration.

[0448] Thus, in particular embodiments of the fourth and fifth aspects of the invention, the pharmaceutical formulation is provided in a pharmaceutically acceptable dosage form, including tablets or capsules, liquid forms for oral administration or injection, suppositories, creams, gels, foams, inhalants (e.g., for intranasal application), or forms suitable for topical administration. For the avoidance of doubt, in such embodiments, the compounds of the invention may be present as solids (e.g., a solid dispersion), liquids (e.g., in solution), or in other forms, such as micelles.

[0449] For example, in the preparation of pharmaceutical formulations for oral administration, the compound may be mixed with solid and powdered ingredients such as lactose, sucrose, sorbitol, mannitol, starch, amylopectin, cellulose derivatives, gelatin or other suitable ingredient, as well as with disintegrating agents and lubricating agents such as magnesium stearate, calcium stearate, sodium stearyl fumarate and polyethylene glycol waxes. The mixture may then be processed into granules or compressed into tablets.

[0450] Soft gelatin capsules may be prepared with capsules containing one or more active compounds (for example, compounds from the first and therefore the second and third aspects of the invention and, optionally, additional therapeutic agents), together with, for example, vegetable oil, fat or other suitable vehicle for soft gelatin capsules. Similarly, hard gelatin capsules may contain this / these compound(s) in combination with powdered solid ingredients such as lactose, sucrose, sorbitol, mannitol, potato starch, corn starch, amylopectin, cellulose derivatives or gelatin.

[0451] Dosage units for rectal administration may be prepared (i) in the form of suppositories containing the compound(s) mixed with a neutral fat base; (ii) in the form of a rectal capsule of Petition 870250102326, dated 07 / 11 / 2025, pp. 69 / 101 62 / 93 gelatin containing the active substance in a mixture with a vegetable oil, paraffin oil or other suitable vehicle for rectal gelatin capsules; (iii) in the form of a ready-to-use micro enema; or (iv) in the form of a dry micro enema formulation to be reconstituted in a suitable solvent immediately before administration.

[0452] Liquid preparations for oral administration may be prepared in the form of syrups or suspensions, for example, solutions or suspensions, containing the compound(s) and the remainder of the formulation consisting of sugar or sugar alcohols and a mixture of ethanol, water, glycerol, propylene glycol and polyethylene glycol. If desired, these liquid preparations may contain coloring agents, flavoring agents, saccharin and carboxymethylcellulose or other thickening agent. Liquid preparations for oral administration may also be prepared in the form of a dry powder to be reconstituted with a suitable solvent before use.

[0453] Solutions for parenteral administration may be prepared as a solution of the compound(s) in a pharmaceutically acceptable solvent. These solutions may also contain stabilizing and / or buffering ingredients and are dispensed in unit doses in the form of ampoules or vials. Solutions for parenteral administration may also be prepared as a dry preparation to be reconstituted with a suitable solvent extemporaneously before use.

[0454] The expert will understand that the compounds of the invention and their pharmaceutically acceptable salts can be administered (for example, as formulations as described above) in varying doses, the appropriate doses being easily determined by a person skilled in the art. Oral, pulmonary, and topical (and subcutaneous, although these dosages may be relatively lower) dosages can range from about 0.01 μg / kg of body weight per day (g / kg / day) to about 200 μg / kg / day, preferably from about 0.01 to about 10 μg / kg / day and, more preferably, from about 0.1 to about 5.0 μg / kg / day. For example, when administered orally, treatment with these compounds may include the administration of formulations that typically contain Petition 870250102326, dated 07 / 11 / 2025, pp. 70 / 101 63 / 93 between 0.01 μg and 2,000 mg, for example, between 0.1 μg and 500 mg or between 1 μg and 100 mg (for example, 20 μg and 80 mg) of the active ingredient(s). When administered intravenously, the most preferred doses range from about 0.001 to about 10 μg / kg / hour during constant rate infusion. Advantageously, treatment may involve administering such compounds and compositions in a single daily dose, or the total daily dosage may be administered in divided doses two, three, or four times a day (for example, twice a day with reference to the doses described in this document, such as a dose of 10 mg, 20 mg, 30 mg, or 40 mg twice a day, or 10 μg, 20 μg, 30 μg, or 40 μg twice a day).

[0455] In any case, one skilled in the art (e.g., a physician) will be able to determine the most appropriate actual dosage for an individual patient, which will likely vary with the route of administration, the type and severity of the condition being treated, as well as the species, age, weight, sex, renal function, hepatic function, and response of the specific patient being treated. The aforementioned dosages are illustrative of the average case; there may, of course, be individual cases where higher or lower dosage ranges are of merit, and such are within the scope of this invention.

[0456] As described above, the expert will understand that treatment with compounds of the first aspect of the invention may further comprise (i.e., be combined with) additional / other treatment(s) for the same condition. In particular, treatment with the compounds of the invention may be combined with other means for the treatment of hyperglycemia or a disorder characterized by hyperglycemia (as defined herein as type 2 diabetes), such as treatment with one or more therapeutic agents useful in the treatment of hyperglycemia or a disorder characterized by hyperglycemia (as defined herein as type 2 diabetes).

[0457] In certain embodiments of the fourth and fifth aspects of the invention, the pharmaceutical composition may also include one or more additional therapeutic agents (i.e., others).

[0458] In more specific modalities, one or more Petition 870250102326, dated 07 / 11 / 2025, pp. 71 / 10164 / 93 Additional therapeutic agents are agents for the treatment of type 2 diabetes, as known to those skilled in the art, such as metformin, sulfonylureas (e.g., carbutamide, acetohexamide, chlorpropamide, tolbutamide, glipizide (Glucotrol), gliclazide, glibenclamide, glyburide (Micronase), glibornuride, gliquidone, glisoxepide, glycopyramide, glimepiride (Amaryl), glimiprime, JB253 or JB558), thiazolidinediones (e.g., pioglitazone, rosiglitazone (Avandia), lobeglitazone (Duvie) and troglitazone (Rezulin)), dipeptidyl peptidase-4 inhibitors (e.g., sitagliptin, vildagliptin, saxagliptin, linagliptin, anagliptin, tenegliptin, alogliptin, trelagliptin, gemigliptin, dutogliptin and omarigliptin), SGLT2 inhibitors (e.g., dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, tofogliflozin, sergliflozin etabonate, remogliflozin etabonate and ertugliflozin) and glucagon-like peptide-1 (GLP-1) analogs.

[0459] A person knowledgeable will understand that combinations of therapeutic agents may also be described as a combination product and / or supplied as a kit of parts.

[0460] In a sixth aspect of the invention, a combined product is provided comprising:

[0461] (A) a compound as defined in the first aspect of the invention; and

[0462] (B) one or more additional therapeutic agents,

[0463] wherein each of components (A) and (B) is formulated in a mixture, optionally with one or more pharmaceutically acceptable adjuvants, diluents or carriers.

[0464] In a seventh aspect of the invention, a kit of parts is provided comprising:

[0465] (a) a compound as defined in the first (or second and / or third) aspect of the invention, (or a pharmaceutical composition comprising the same) or a pharmaceutical composition as defined in the fourth or fifth aspect of the invention; and

[0466] (b) one or more other therapeutic agents, Petition 870250102326, dated 07 / 11 / 2025, pp. 72 / 101 65 / 93 optionally in a mixture with one or more pharmaceutically acceptable adjuvants, diluents or carriers,

[0467] which components (a) and (b) are each supplied in a form suitable for administration together with each other.

[0468] In certain embodiments (for example, of the sixth and seventh aspects of the invention), the additional therapeutic agent is a therapeutic agent that is useful for the treatment of hyperglycemia or a disorder characterized by hyperglycemia (for example, type 2 diabetes), as known to those skilled in the art (such as those described in this document).

[0469] For example, in certain embodiments of the fourth and fifth aspects of the invention, the additional therapeutic agent is an agent that:

[0470] (i) is able to reduce blood sugar levels; and / or

[0471] (ii) is an insulin sensitizer; and / or

[0472] (iii) is able to increase insulin release,

[0473] which agents will be easily identified by those skilled in the art and include, in particular, those therapeutic agents that are commercially available (for example, agents that are the subject of a marketing authorization in one or more territories, such as a European or North American marketing authorization).

[0474] A person knowledgeable will understand that references to therapeutic agents capable of reducing blood glucose levels may refer to compounds capable of reducing blood glucose levels by at least 10% (such as at least 20%, at least 30% or at least 40%, for example, at least 50%, at least 60%, at least 70% or at least 80%, for example, at least 90%) when compared to blood glucose levels before treatment with the relevant compound.

[0475] In alternative embodiments of the sixth and seventh aspects of the invention, the additional therapeutic agent is an agent for the treatment Petition 870250102326, dated 07 / 11 / 2025, pp. 73 / 101 66 / 93 or prevention of non-alcoholic fatty liver disease (such as NASH), whose agents will be easily identified by those skilled in the art and include, in particular, therapeutic agents that are commercially available (e.g., agents that are the subject of a marketing authorization in one or more territories, such as a European or North American marketing authorization).

[0476] In alternative embodiments of the sixth and seventh aspects of the invention, the additional therapeutic agent is an agent for the treatment of a disease or disorder whose treatment is mediated by the activation of the β2 adrenergic receptor, which diseases and disorders will include those described in this document and whose agents will be readily identified by those with expertise in the field and will include, in particular, commercially available therapeutic agents (for example, agents subject to a marketing authorization in one or more territories, such as a European or North American marketing authorization). PREPARATION OF COMPOUNDS / COMPOSITIONS

[0477] The pharmaceutical compositions / formulations, combination products and kits as described herein may be prepared in accordance with standard and / or accepted pharmaceutical practice.

[0478] Thus, in a further aspect of the invention, a process is provided for the preparation of a pharmaceutical composition / formulation, as defined above, which process comprises combining a compound of the invention, as defined above, with one or more pharmaceutically acceptable adjuvants, diluents or carriers.

[0479] In other aspects of the invention, a process is provided for preparing a combined product or kit of parts as defined above, which process comprises combining a compound of the invention, as defined above, or a pharmaceutically acceptable salt thereof with another therapeutic agent that is useful in the treatment of hyperglycemia or a disorder characterized by hyperglycemia (e.g., type 2 diabetes), and at least one pharmaceutically acceptable adjuvant, diluent or carrier.

[0480] As used here, the references to be placed in Petition 870250102326, dated 07 / 11 / 2025, pp. 74 / 101 The 67 / 93 association means that the two components are suitable for administration together.

[0481] Thus, with regard to the process of preparing a parts kit as defined above, when putting the two components “in association” with each other, it is included that the two components of the parts kit can be:

[0482] (i) supplied as separate formulations (i.e., independently of each other), which are subsequently combined for use together in combination therapy; or

[0483] (ii) packaged and presented together as separate components of a “combination pack” for use together with each other in combination therapy.

[0484] The compounds defined in the first aspect of the invention (i.e., the compounds of the invention) can be prepared according to techniques well known to those skilled in the art, such as those described in the examples provided below.

[0485] For example, a process is provided for the preparation of a compound of formula I, or a pharmaceutically acceptable salt thereof, wherein R1 represents H and the remaining substituents are defined in the first aspect of the invention, the process comprising:

[0486] (i) reaction of a compound of formula II (Z)n II

[0487] wherein the ring A, R1, Z and en are defined in this document, and wherein M1 represents a suitable metal or metal halide, with a compound of formula III THE Q2 Q3Q4Q III Petition 870250102326, dated 07 / 11 / 2025, pp. 75 / 101 68 / 93

[0488] where Q1a Q5 (and therefore the Q ring) are defined in this document, under conditions known to experts;

[0489] (ii) reaction of a compound of formula IV q2 QL, M2 Q§Q5 IV

[0490] where Q1a Q5 are defined in this document, and where M2 represents a suitable metal or metal halide, with a compound of formula V HR nj_ 7^A)-(Z)n

[0491] wherein the ring A, R1, Z and en are defined in this document, under conditions known to experts.

[0492] The compounds of formulas II, III, IV, V are commercially available, are known in the literature, or can be obtained by analogy with the processes described herein or by conventional synthetic procedures, according to standard techniques, from available starting materials (e.g., benzaldehydes, styrenes or phenacyl bromides appropriately substituted (or phenacyl chloride and the like)) using appropriate reagents and reaction conditions. In this regard, the specialist may consult, among others, “Comprehensive Organic Synthesis”, by B.M. Trost and I. Fleming, Pergamon Press, 1991. Other references that may be employed include “Science of Synthesis”, Volumes 9-17 (Hetarenes and Related Ring Systems), Georg Thieme Verlag, 2006.

[0493] The substituents Y and Z, as defined above, may be modified one or more times, after or during the processes described above for the preparation of compounds of formula I by means of methods well known to those skilled in the art. Examples of such methods include substitutions, reductions, oxidations, dehydrogenations, alkylations, Petition 870250102326, dated 07 / 11 / 2025, pp. 76 / 101 69 / 93 dealkylations, acylations, hydrolyses, esterifications, etherifications, halogenations and nitrations. The precursor groups can be changed to a different group, or to the groups defined in formula I, at any time during the reaction sequence. The specialist may also consult “Comprehensive Organic Functional Group Transformations”, by A.R. Katritzky, O. Meth-Cohn and C.W. Rees, Pergamon Press, 1995 and / or “Comprehensive Organic Transformations”, by R.C. Larock, WileyVCH, 1999.

[0494] These compounds can be isolated from their reaction mixtures and, if necessary, purified using conventional techniques known to those skilled in the art. Thus, the processes for preparing the compounds of the invention, as described in this document, may include, as a final step, the isolation and, optionally, the purification of the compound of the invention (for example, the isolation and, optionally, the purification of the compound of formula I).

[0495] The expert will understand that compounds of formula I with specific stereochemistry can be obtained by reacting suitable starting materials with the required stereochemistry in processes described in this document. Furthermore, the expert will understand that suitable starting materials with the required stereochemistry can be prepared by analogy with the processes described in this document.

[0496] Skilled in the art will understand that, in the processes described above and below, the functional groups of intermediate compounds may need to be protected by protecting groups. The protection and deprotection of functional groups may occur before or after a reaction in the aforementioned schemes.

[0497] Protecting groups can be applied and removed in accordance with techniques well known to those skilled in the art and as described below. For example, protected compounds / intermediates described herein can be chemically converted into unprotected compounds using standard deprotection techniques. The type of chemistry involved will determine the Petition 870250102326, dated 07 / 11 / 2025, pp. 77 / 101 70 / 93 The need for and type of protecting groups, as well as the sequence for carrying out the synthesis, is crucial. The use of protecting groups is fully described in “Protective Groups in Organic Synthesis”, 3rd edition, TW Greene & PGM Wutz, Wiley-Interscience (1999).

[0498] The compounds described herein (in particular, compounds defined in the first and therefore second and third aspects of the invention) may have the advantage of being more effective, less toxic, having a longer duration of action, being more potent, producing fewer side effects, being more easily absorbed and / or having a better pharmacokinetic profile (e.g., greater oral bioavailability and / or lower clearance) and / or having other useful pharmacological, physical or chemical properties compared to compounds known in the prior art, whether for use in the indications mentioned above or otherwise. In particular, such compounds may have the advantage of being more effective and / or exhibiting advantageous properties in vivo.

[0499] Without wanting to get bogged down in theory, it is believed that the compounds described here are potent agonists of the e2-adrenergic receptor, which allows for increased glucose uptake in skeletal muscle cells.

[0500] Furthermore, the compounds described in this document are believed to be ε2-adrenergic receptor agonists without (or with only a minimal effect on) the induction of cAMP production. This is believed to allow for effects such as increased glucose uptake in skeletal muscle cells with lower levels of side effects than would result from other treatments. Additionally, the combination of the compounds described herein with other therapeutic agents, such as those capable of reducing blood glucose levels, is believed to provide an effective combination therapy. EXAMPLES

[0501] The present invention is illustrated by the following examples.

[0502] The chemicals and reagents were obtained from commercial suppliers and were used as received, unless otherwise indicated in Petition 870250102326, dated 07 / 11 / 2025, pp. 78 / 101 71 / 93 contrary. All reactions involving moisture-sensitive reagents were carried out in dry glassware in an oven or flame under positive nitrogen or argon pressure. ABBREVIATIONS

[0503] The abbreviations used in this document are known to those skilled in the art. In particular, the following abbreviations may be used here.

[0504] atmosphere

[0505] aqueous water

[0506] Pd-C palladium on carbon

[0507] at room temperature

[0508] sat saturated EXAMPLE OF COMPOUNDS

[0509] In the event of a discrepancy between the nomenclature and the structure of the compounds, as graphically represented, the latter shall prevail (unless contradicted by any experimental details that may be provided and / or unless it is clear from the context). EXAMPLE 1: N-(1-((CIS)-4-(((R)-2-(3-FLUOROPHENYL)-2HYDROXYETHI L)AMINO)CYCLO-HEXY L)-2-METHYLPROPAN-2-YL)ACETAMI DA

[0510] (a) tert-Butyl ((cis)-4-(hydroxymethyl)cyclohexyl)carbamate

[0511] The boron dimethyl sulfide complex (2.42 mL, (25.48 mmol) was added slowly, drop by drop, to a solution cooled with ice. Petition 870250102326, dated 07 / 11 / 2025, pp. 79 / 101 72 / 93 of (cis)-4-((tert-butoxycarbonyl)amino)cyclohexane-1-carboxylic acid (1.00 g, 4.11 mmol) in THF (30 mL). The cooling bath was removed and the mixture was stirred at room temperature for 3 h. MeOH (5 mL) was added and the mixture was concentrated. MeOH (1 mL) was added to the residue and the mixture was concentrated. This procedure was repeated two more times. NaOH (aq, 2 M) was added to the residue and it was extracted with EtOAc. The combined extracts were washed with brine, dried (Na2SO4) and concentrated to give the compound of the subtitle (1.88 g, 99%), which was used in the next step without further purification.

[0512] (b) methanesulfonate of ((cis)-4-((tert-Butoxycarbonyl)amino)cyclohexyl)methyl

[0513] Methanesulfonyl chloride (0.70 mL, 9.00 mmol) was added dropwise to an ice-cooled, stirred mixture of tert-butyl ((cis)-4(hydroxymethyl)cyclohexyl)carbamate (1.88 g, 8.18 mmol), triethylamine (1.48 mL, 10.63 mmol), and CH2Q2 (50 mL). The mixture was stirred at 0 °C for 2 hours and H2O was added. The layers were separated, and the aqueous phase was extracted with CH2Cl2. The combined organic phases were washed with H2O and brine, dried (Na2SO4), and concentrated to give the subtitle compound (2.50 g, 99%), which was used in the next step without further purification.

[0514] (c) tertButyl ((cis)-4-(cyanomethyl)cyclohexyl)carbamate

[0515] NaCN (1.20 g, 24.40 mmol) was added to a solution of ((cis)-4-((tert-butoxycarbonyl)amino)cyclohexyl)methylmethanesulfonate (2.50 g, 8.13 mmol) in DMSO (20 mL). The mixture was stirred at 90 °C for 4 hours and cooled to room temperature. Brine was added and the mixture was extracted with EtOAc. Petition 870250102326, dated 07 / 11 / 2025, pp. 80 / 101 73 / 93 The combined extracts were washed with brine, dried (Na2SO4) and concentrated. The residue was purified by chromatography to give the compound of the subtitle (1.66 g, 85%).

[0516] (d) tert-Butyl ((cis)-4-(2-amino-2-methylpropyl)cyclohexyl)carbamate H H BocNk / II ηκι L

[0517] A mixture of CeCl3 (4.99 g, 20.25 mmol) and THF (34) was vigorously stirred for 45 minutes at ta. The suspension was cooled to -78 °C, and MeLi (1.6 M in Et2O, 12.66 mL, 20.25 mmol) was added dropwise. The mixture was stirred at -78 °C for 30 minutes and a solution of tert-butyl ((cis)-4-(cyanomethyl)cyclohexyl)carbamate (0.95 g, 4.00 mmol) in THF (8 mL) was added dropwise and the mixture was stirred for 30 minutes at -78 °C and for 3 hours at -65 °C. NH3 (aq, sat) was added dropwise at -65 °C and the mixture was allowed to warm to ta and filtered through a Celite pad, which was washed with CH2Q2. The combined filtrates were dried (Na2SO4) and concentrated. The residue was dissolved in CH2Cl2 (40 mL) and AcOH (1.15 mL, 20 mmol) was added slowly, drop by drop, and the mixture was stirred at room temperature for 30 minutes and concentrated. CH2Cl2 was added to the residue and the mixture was concentrated. This procedure was repeated three times.The residue was ground with MeCN, sonicated, and filtered. The residue was divided between CH2Q2 and NaHCO3 (aq, sat), the layers were separated, and the aq phase was extracted with CH2Q2. The combined organic phases were washed with brine, dried (Na2SO4), and concentrated to give the compound of the subtitle (0.72 g, 66%).

[0518] (e) tert-Butyl((cis)-4-(2-acetamido-2-methylpropyl)cyclohexyl)carbamate

[0519] Et3N (134 μL, 0.96 mmol) followed by sodium chloride Petition 870250102326, dated 07 / 11 / 2025, pp. 81 / 101 74 / 93 acetyl (58 μL, 0.81 mmol) were added to a solution of tert-butyl ((cis)-4-(2-amino-2-methylpropyl)cyclohexyl)carbamate (200 mg, 0.74 mmol) in CH2O2 (5 mL) at 0 °C. The mixture was stirred at 0 °C for 1 hour and diluted with CH2O2. NaHCO3 (aq, sat) was added, the layers were separated, and the aq phase was extracted with CH2Cl2. The combined organic phases were dried (Na2SO4) and concentrated. The residue was purified by chromatography to give the compound of the subtitle (218 mg, 94%).

[0520] (f) N-(1-((cis)-4-Aminocyclohexyl)-2-methylpropan-2yl)acetamide

[0521] Amberlyst 15 resin (300 mg) was washed with MeOH was added to a stirred solution of tert-butyl (cis)-4-(2-acetamido-2-methylpropyl)cyclohexyl)carbamate (100 mg, 0.32 mmol) in CH2O2 (1 mL) and the mixture was stirred at room temperature overnight. Another portion of Amberlyst 15 resin (200 mg) was added and the mixture was stirred at room temperature for 2 days. The resin was filtered and washed with MeOH. The washed resin was placed in 1 mL of 7N NH3 solution in MeOH. The mixture was stirred for 30 minutes. The resin was then filtered and washed with MeOH and the filtrate was concentrated to give the compound of the subtitle (51 mg, 75%), which was used in the next step without further purification.

[0522] (g) N-(1-(( cis )-4-((( R )-2-(3-Fluorophenyl)-2hydroxyethyl)amino)cyclohexyl)-2-methylpropan-2-yl)acetamide

[0523] A mixture of N-(1-((cis)-4-aminocyclohexyl)-2methylpropan-2-yl)acetamide (45 mg, 0.21 mmol), (R)-2-(3-fluorophenyl)oxirane (38 mg, A mixture of 0.28 mmol) and iPrOH (0.5 mL) was stirred at 80 °C for 16 h. The mixture was concentrated and the residue was purified by chromatography to obtain the title compound (30 mg, Petition 870250102326, dated 07 / 11 / 2025, pp. 82 / 101 75 / 93 40%).

[0524] 1H NMR (400 MHz, CDCI3) δ 7.34 - 7.26 (m, 1H), 7.15 - 7.07 (m, 2H), 6.95 (tdd, J = 8.5, 2.6, 1.1 Hz, 1H), 5.18 (s, 1H), 4.66 (dd, J = 9.0, 3.6 Hz, 1H), 2.96 (dd, J = 12.2, 3.6 Hz, 1H), 2.70 - 2.63 (m, 1H), 2.60 (dd, J = 12.2, 9.0 Hz, 1H), 1.90 (s, 3H), 1.70 - 1.66 (m, 2H), 1.66 - 1.56 (m, 2H), 1.56 - 1.44 (m, 5H), 1.44 - 1.36 (m, 2H), 1.31 (s, 6H). EXAMPLE 2: N-(1-((CIS)-4-(((R)-2-(3-FLUOROPHENYL)-2-HYDROXYETHYL)AMINO)CYCLO-HEXYL)-2-METHYLPROPAN-2-YL)METHANESULFONAMIDE

[0525] (a) N-(1-((cis)-4-Aminocyclohexyl)-2-methylpropan-2yl)methanesulfonamide H2N tert-butyl ((cis)-4-(2-methyl-2(methylsulfonamido)propyl)cyclohexyl)carbamate, prepared according to the procedure of Example 1, using methanesulfonyl chloride in Step (e), (0.100 g, 0.287 mmol), NaI (0.056 g, 0.373 mmol), CeCl3*7H2O (0.16 g, 0.43 mmol) and MeCN (2 mL) were stirred for 4 hours at 80 °C. CHCb (10 mL) and NaOH (aq, 1 M, 15 mL) were added and the mixture was stirred until colorless. The layers were separated and the organic phase was washed with water. The combined aq phases were extracted with iPrOH / CHCh (1 / 4) and the organic phases were combined, dried (Na2SO4) and concentrated. The residue was purified by reverse-phase chromatography to obtain the compound from the subtitle (55 mg, 77%).

[0527] (b) N-(1-((cis)-4-(((R)-2-(3-Fluorophenyl)-2hydroxyethyl)amino)cyclohexyl)-2-methylpropan-2-yl)methanesulfonamide Petition 870250102326, dated 07 / 11 / 2025, pages 83 / 101 76 / 93

[0528] The title compound was prepared from N-(1((cis)-4-aminocyclohexyl)-2-methylpropan-2-yl)methanesulfonamide according to the procedure in Example 1, Step (g).

[0529] 1H NMR (400 MHz, CDCI3) δ 7.33 - 7.27 (m, 1H), 7.14 - 7.08 (m, 2H), 6.95 (tdd, J = 8.5, 2.6, 1.1 Hz, 1H), 4.71 (dd, J = 9.1, 3.5 Hz, 1H), 4.22 (s, 1H), 3.02 (s, 3H), 2.97 (dd, J = 12.2, 3.6 Hz, 1H), 2.74 - 2.68 (m, 1H), 2.63 (dd, J = 12.2, 9.1 Hz, 1H), 1.69 - 1.59 (m, 3H), 1.59 - 1.50 (m, 6H), 1.50 - 1.40 (m, 2H), 1.37 (s, 6H). EXAMPLE 3: N-(1-((CIS)-4-(((R)-2-(5-FLUOROPYRIDINE-3-YL)2-HYDROXYETHYL)AMINO)CYCLOHEXYL)-2-METHYLPROPAN-2-YL)ACETAMIDE

[0530] The title compound was prepared according to the procedure of Example 1, using (R )-3-fluoro-5-(oxiran-2-yl)pyridine in Step (g).

[0531] 1H NMR (400 MHz, CDCl3) δ 8.40 - 8.37 (m, 1H), 8.36 (d, J = 2.8 Hz, 1H), 7.55 - 7.43 (m, 1H), 5.22 (s, 1H), 4.69 (dd, J = 9.2, 3.6 Hz, 1H), 2.98 (dd, J = 12.3, 3.7 Hz, 1H), 2.69 - 2.62 (m, 1H), 2.58 (dd, J = 12.3, 9.2 Hz, 1H), 1.89 (s, 3H), 1.72 - 1.65 (m, 2H), 1.65 - 1.43 (m, 7H), 1.43 - 1.34 (m, 2H), 1.30 (s, 6H). EXAMPLE 4: N-(1-((CIS)-4-(((R)-2-(5-FLUOROPYRIDIN-3-YL)-2-HYDROXYETHYL)AMINO)CYCLO-HEXYL)-2-METHYLPROPAN-2YL)METHANESULFONAMIDE Petition 870250102326, dated 07 / 11 / 2025, pages 84 / 101 77 / 93

[0532] The title compound was prepared according to the procedure of Example 1, using methanesulfonyl chloride in Step (e) and (R)2-(3-fluorophenyl)oxirane in Step (g).

[0533] RMN de1H (400 MHz, CDCl3) δ 8.44 - 8.39 (m, 1H), 8.38 (d, J = 2.8 Hz, 1H), 7.55 - 7.46 (m, 1H), 4.76 (dd, J = 9.2, 3.5 Hz, 1H), 4.21 (s, 1H), 3.07 - 2.98 (m, 4H), 2.76 - 2.69 (m, 1H), 2.62 (dd, J = 12.3, 9.2 Hz, 1H), 1.70 1.59 (m, 3H), 1.59 - 1.50 (m, 6H), 1.50 - 1.41 (m, 2H), 1.38 (s, 6H). EXEMPLO 5(R)-1-(4-((2-(3-FLUOROFENIL)-2HIDROXIETIL)AMINO)-4-METILPIPERIDIN-1-IL)ETAN-1-ONA

[0534] (a) (1-acetil-4-metilpiperidin-4-il)carbamato from tercButila L NH

[0535] Et3N (0.33 mL, 2.34 mmol) followed by acetyl chloride (0.14 mL, 1.98 mmol) were added to a solution of tert-butyl (4-methylpiperidin-4-yl)carbamate (0.385 g, 1.80 mmol) in CH2O2 (5 mL) at 0 °C. The mixture was stirred at 0 °C for 1 hour and diluted with CH2O2. NaHCO3 (aq, sat) was added, the layers were separated, and the aq phase was extracted with CH2Cl2. The combined organic phases were dried (Na2SO4) and concentrated. The residue was purified by chromatography to give the compound of the subtitle (0.36 g, 77%).

[0536] (b) 1-(4-Amino-4-methylpiperidin-1-yl)ethan-1-one Petition 870250102326, dated 07 / 11 / 2025, pp. 85 / 101 78 / 93 h2n.

[0537] Amberlyst 15 resin (0.5 g) was washed with MeOH and added to a stirred solution of tert-butyl (1-acetyl-4-methylpiperidin-4-yl)carbamate (0.10 g, 0.39 mmol) in CH2O2 (1 mL) and the mixture was stirred at room temperature for 48 hours. h. The resin was washed with CH2Cl2 and treated with NH3 (7 M in MeOH, 1 mL) and the paste was stirred at room temperature for 30 minutes. The resin was filtered and washed with MeOH, and the combined filtrates were concentrated to give the compound of the subtitle (0.50 g, 82%).

[0538] (d) (R )-1-(4-((2-(3-Fluorophenyl)-2-hydroxyethyl)amino)4-methylpiperidin-1-yl)ethan-1-one

[0539] A mixture of 1-(4-amino-4-methylpiperidin-1yl)ethan-1-one (43 mg, 0.28 mmol), (R)-2-(3-fluorophenyl)oxirane (49 mg, 0.36 mmol) and iPrOH (0.63 mL) was stirred at 80 °C for 16 h. The mixture was concentrated and the residue was purified by chromatography to obtain the title compound (36 mg, 44%).

[0540] 1H NMR (400 MHz, CDCl3) δ 7.35 - 7.27 (m, 1H), 7.24 - 7.16 (m, 2H), 7.03 - 6.92 (m, 1H), 5.35 (dd, J = 10.4, 2.0 Hz, 1H), 3.18 (dd, J = 12.1, 2.1 Hz, 1H), 3.05 - 2.96 (m, 1H), 2.96 - 2.83 (m, 7H), 1.97 - 1.89 (m, 1H), 1.89 - 1.79 (m, 4H), 1.79 - 1.65 (m, 4H), 1.65 - 1.51 (m, 2H), 1.47 (s, 3H), 1.44 (s, 3H). EXAMPLE 6: (R)-1-(3-FLUOROPHENYL)-2-((4-METHYL-1(METHYLSULFONYL)PIPERIDIN-4-YL)AMINO)ETHAN-1-OL

[0541] The title compound was prepared in accordance with Petition 870250102326, dated 07 / 11 / 2025, pages 86 / 101 79 / 93 the procedures of Example 5, using methanesulfonyl chloride in Step (a).

[0542] 1H NMR (400 MHz, CDCh) δ 7.35 - 7.27 (m, 1H), 7.15 - 7.06 (m, 2H), 6.96 (tdd, J = 8.4, 2.5, 1.2 Hz, 1H), 4.65 (dd, J = 8.1, 3.8 Hz, 1H), 3.38 - 3.21 (m, 2H), 3.21 - 3.04 (m, 2H), 2.86 (dd, J = 11.7, 3.8 Hz, 1H), 2.75 (s, 3H), 2.58 (dd, J = 11.7, 8.2 Hz, 1H), 1.72 - 1.52 (m, 4H), 1.12 (s, 3H). EXAMPLE 7: (R)-1-(4-((2-(5-FLUOROPYRIDINE-3-IL)-2HYDROXYETYL)AMINO)-4-MEthyLPYPERIDIN-1-IL)ETHAN-1-ONA

[0543] The title compound was prepared in accordance with the procedure of Example 5, using (R )-3-fluoro-5-(oxiran-2-yl)pyridine in Step (d).

[0544] NMR of1H (300 MHz, CDCh) δ 8.50 − 8.24 (m, 2H), 7.59 − 7.37 (m, 1H), 4.70 (dd, J = 8.7, 3.7 Hz, 1H), (3.59 − 3.24 (m, 3H), 2.95 (ddd, J = 11.9, 4.8, 3.7 Hz, 1H), 2.58 (dt, J = 11.9, 8.9 Hz, 1H), 2.08 (s, 3H), 1.58 - s 1.4). EXAMPLE 8: (R)-1-(5-FLUOROPYRIDIN-3-IL)-2-((4-METYL-1(METHYLSULFONYL)PIPERIDINE-4-IL)AMINO)ETHAN-1-DICHLORIDRATE .2HCl

[0545] The free base of the title compound was prepared according to the procedure of Example 1 using methanesulfonyl chloride in Step (a) and (R)-3-fluoro-5-(oxiran-2-yl)pyridine in Step (d) and was dissolved in CH2O2. HCl (2 M in Et2O) was added and the mixture was concentrated to give the dihydrochloride salt.

[0546] 1H NMR (400 MHz, CDCh) δ 8.57 - 8.49 (m, 1H), 8.46 (d, J = 2.7 Hz, 1H), 7.86 - 7.75 (m, 1H), 5.08 (dd, J = 9.9, 3.1 Hz, 1H), 3.76 - 3.62 Petition 870250102326, dated 07 / 11 / 2025, pp. 87 / 101 80 / 93 (m, 2H), 3.29 (d, J = 3.3 Hz, 1H), 3.15 (dd, J = 12.4, 9.9 Hz, 1H), 3.07 - 2.97 (m, 2H), 2.89 (s, 3H), 2.04 - 1.88 (m, 4H), 1.46 (s, 3H). EXAMPLE 9: 2-(((TRANS)-4-(((R)-2-(3-FLUOROPHENYL)-2-HYDROXYETHYL)AMINO)CYCLO-HEXYL)OXY)ETHYL ACETATE F

[0547] ethyl hexyl)oxy)acetate H BOC'N'

[0548] Ethyl diazoacetate (0.59 mL, 4.88 mmol) was slowly added to a stirred mixture of tert-butyl ((trans)-4-hydroxycyclohexyl)carbamate (0.50 g, 2.32 mmol), rhodium acetate dimer (31 mg, 70 μmol) and CH2Q2 (25 mL) at room temperature. The mixture was stirred at room temperature for 15 minutes and concentrated. The residue was purified by chromatography to give the subtitle compound (0.55 g, 79%).

[0549] (b) ethyl 2-(((trans)-4-aminocyclohexyl)oxy)acetate OHHN (a) 2-((( trans )-4-(( tert- butoxycarbonyl)amino)cycloH Boc'N'·

[0550] CF3CO2H (1.41 mL, 18.4 mmol) was added to a stirred solution of ethyl 2-(((trans)-4-((tert-butoxycarbonyl)amino)cyclohexyl)oxy)acetate (0.55 g, 1.84 mmol) in CH2Cl2 (2.5 mL) at room temperature. The mixture was stirred at room temperature for 30 minutes and concentrated. The residue was dissolved in CH2O2 and washed with H2O. The layers were separated and NaHCO3 (aq, sat) was added to the aq phase, which was then extracted with iPrOH:CH2Cl2 (1:3). The combined organic phases were dried (Na2SO4) and concentrated to obtain the compound of the subtitle (0.33 g, 90%). Petition 870250102326, dated 07 / 11 / 2025, pp. 88 / 101 81 / 93

[0551] (c) 2-((( trans )-4-((( R )-2-(3-fluorophenyl)-2-hydroxyethyl)amino)cyclohexyl)oxy)ethyl acetate H2N / , F H N„

[0552] The title compound was prepared from ethyl 2(((trans)-4-aminocyclohexyl)oxy)acetate (0.12 g, 0.60 mmol), (R)-2-(3fluorofenil)oxirano (38 mg, 0.28 mmol) and iPrOH (0.5 mL) from acordo with Exemplo 1, Etapa (d), 85 mg (42%).

[0553] RMN de1H (300 MHz, CDCb) δ 7.36 - 7.27 (m, 1H), 7.16 - 7.02 (m, 2H), 6.95 (tdd, J = 8.5, 2.6 Hz, 1H), 4.68 (dd, J = 9.0, 3.6 Hz, 1H), 4.21 (q, J = 7.2 Hz, 2H), 4.08 (s, 2H), 3.37 - 3.25 (m, 1H), 2.97 (dd, J = 12.2, 3.6 Hz, 1H), 2.73 - 2.59 (m, 1H), 2.52 (tt, J = 10.3, 3.6 Hz, 1H), 2.14 - 1.86 (m, 4H), 1.41 - 1.24 (m, 5H), 1.22 - 1.02 (m, 2H). EXEMPLO 10: ÁCIDO 2-(((TRANS)-4-(((R)-2-(3FLUOROFENIL)-2-HIDROXIETIL)AMINO)CICLO-HEXIL)OXI)ACÉTICO

[0554] A solution of LiOH^O (31 mg, 0.73 mmol) in H2O (3 mL) was added to a stirred and ice-cooled solution of 2-(((trans)4-(((R)-2-(3-fluorophenyl)-2-hydroxyethyl)amino)cyclohexyl)oxy)acetate ethyl (62 mg, 0.18 mmol) in THF (3 mL) at 0 °C. The cooling bath was removed and the mixture was stirred at room temperature for 16 h. AcOH (52 pl, 0.91) mmol was added and the mixture was stirred at room temperature for 15 minutes, filtered through a cotton buffer, which was washed with H2O:MeCN (1:1). The combined filtrates were concentrated and the residue was purified using reverse-phase chromatography to obtain the title compound (40 mg, 70%).

[0555] 1H NMR (300 MHz, CD3OD) δ 7.49 - 7.37 (m, Petition 870250102326, dated 07 / 11 / 2025, pages 89 / 101 82 / 93 1H), 7.31 - 7.15 (m, 2H), 7.06 (td, J = 8.5, 2.6 Hz, 1H), 4.97 (dd, J = 10.3, 3.0 Hz, 1H), 3.91 (s, 2H), 3.48 - 3.36 (m, 1H), 3.25 (dd, J = 12.6, 3.0 Hz, 1H), 3.17 - 3.01 (m, 2H), 2.33 - 2.07 (m, 4H), 1.60 - 1.41 (m, 2H), 1.41 - 1.19 (m, 2H). EXAMPLE 11: N-((CIS)-4-(((R)-2-(3-FLUOROPHENYL)-2-HYDROXYETHYL)AMINO)CYCLOHEXYL)ACETAMIDE

[0556] The title compound was prepared from tert-butyl ((cis)4-aminocyclohexyl)carbamate according to the procedures of Example 5.

[0557] [α^25= -11.3 (c 1.00, MeOH)

[0558] 1H NMR (400 MHz, CD3OD) δ 7.43 - 7.29 (m, J = 1H), 7.24 - 7.10 (m, 2H), 7.05 - 6.93 (m, 1H), 4.78 (dd, J = 9.1, 3.8 Hz, 1H), 3.92 3.79 (m, 1H) 1.46 (m, 4H). EXAMPLE 12: N-((CIS)-4-(((R)-2-(5-FLUOROPYRIDINE-3-IL)-2-

[0559] The title compound was prepared from tert-butyl ((cis)4-aminocyclohexyl)carbamate according to the procedures of Example 5, using (R)-3-fluoro-5-(oxiran-2-yl)pyridine in Step (d).

[0560] [α] d25= -19.3 (c 1.10, MeOH).

[0561] 1H NMR (400 MHz, CD3OD) δ 8.49 - 8.41 (m, 1H), 8.40 - 8.33 (m, 1H), 7.77 - 7.60 (m, 1H), 4.86 - 4.83 (m, 1H), 3.92 - 3.73 (m, 1H), 2.86 (dd, J = 12.2, 4.0 Hz, 1H), 2.77 (dd, J = 12.1, 8.7 Hz, 1H), 2.72 - 2.61 (m, 1H), 1.95 (s, 3H), 1.77 - 1.64 (m, 4H), 1.64 - 1.50 (m, 4H). Petition 870250102326, dated 07 / 11 / 2025, pp. 90 / 101 83 / 93 EXAMPLE 13: N-((CIS)-4-(((R)-2-(3-FLUOROPHENYL)-2-HYDROXYETHYL)AMINO)CYCLOHEXYL)METHANESULFONAMIDE HYDROCHLORIDE u OHH.HCl

[0562] The title compound was prepared from tert-butyl ((cis)4-aminocyclohexyl)carbamate according to the procedures of Example 5, using methanesulfonyl chloride in Step (a). The free base was dissolved in CH2Q2 and the title hydrochloride salt was obtained by adding HCl (2 M in Et2O) and collecting and drying the precipitate.

[0563] Md25= -9.8 (c 0.81, CHCl3).

[0564] 1H NMR (400 MHz, CDCb) δ: 9.43 (br s, 1H), 8.28 (br s, 1H), 7.32 - 7.22 (m, 1H), 7.20 - 7.12 (m, 2H), 6.99 - 6.91 (m, 1H), 6.49 (d, J = 6.7 Hz, 1H), 5.65 - 5.53 (m, 1H), 5.41 (d, J = 10.1 Hz, 1H), 3.68 - 3.58 (m, 1H), 3.37 - 3.21 (m, 1H), 3.21 - 3.04 (m, 2H), 2.98 (s, 3H), 2.28 - 1.94 (m, 6H), 1.64 (s, 2H). EXAMPLE 14: N-((CIS)-4-(((R)-2-(5-FLUOROPYRIDINE-3-YL)-2-HYDROXYETHYL)AMINO)CYCLOHEXYL)METHANESULFONAMIDE

[0565] The title compound was prepared from tert-butyl ((cis)4-aminocyclohexyl)carbamate according to the procedures of Example 5, using methanesulfonyl chloride in Step (a) and (R)-3-fluoro-5-(oxiran2-yl)pyridine in Step (d).

[0566] [a]D25= -21.3 (c 0.80, MeOH).

[0567] 1H NMR (400 MHz, CD3OD) δ 8.52 - 8.43 (m, 1H), 8.43 - 8.35 (m, 1H), 7.78 - 7.63 (m, 1H), 4.95 (dd, J = 9.3, 3.6 Hz, 1H), 3.57 3.50 (m, 1H), 3.02 (dd, J = 12.3, 3.6 Hz, 1H), 2.95 (s, 3H), 2.91 (dd, J = 12.3, 9.3 Hz, 1H), 2.87 - 2.80 (m, 1H), 1.92 - 1.75 (m, 4H), 1.75 - 1.55 (m, 4H). Petition 870250102326, dated 07 / 11 / 2025, pp. 91 / 101 84 / 93 EXAMPLE 15: N-((TRANS)-4-(((R)-2-(3-FLUOROPHENYL)-2-HYDROXYETHYL)AMINO)CYCLOHEXYL)ACETAMIDE

[0568] The title compound was prepared from tert-butyl ((trans)-4-aminocyclohexyl)carbamate according to the procedures in Example 5.

[0569] Md25= -8.3 (c 1.62, MeOH).

[0570] 1H NMR (400 MHz, CD3OD) δ 7.40 - 7.29 (m, 1H), 7.23 - 7.09 (m, 2H), 7.05 - 6.93 (m, 1H), 4.76 (dd, J = 9.2, 3.6 Hz, 1H), 3.70 3.53 (m, 1H), 2.83 (dd, J = 12.1, 3.7 Hz, 1H), 2.72 (dd, J = 12.1, 9.2 Hz, 1H), 2.59 2.42 (m, 1H), 2.03 - 1.91 (m, 4H), 1.91 (s, 3H), 1.36 - 1.14 (m, 4H). EXAMPLE 16: N-((TRANS)-4-(((R)-2-(5-FLUOROPYRIDINE-3YL)-2-HYDROXYETHYL)AMINO)CYCLOHEXYL)ACETAMIDE

[0571] The title compound was prepared from tert-butyl ((trans)-4-aminocyclohexyl)carbamate according to the procedures of Example 5, using (R)-3-fluoro-5-(oxiran-2-yl)pyridine in Step (d).

[0572] [α] d25= -14.7 (c 1.22, MeOH).

[0573] 1H NMR (400 MHz, CD3OD) δ 8.47 - 8.41 (m, 1H), 8.40 - 8.36 (m, 1H), 7.76 - 7.61 (m, 1H), 4.86 - 4.81 (m, 1H), 3.69 - 3.53 (m, 1H), 2.91 (dd, J = 12.2, 3.8 Hz, 1H), 2.80 (dd, J = 12.2, 9.0 Hz, 1H), 2.62 - 2.46 (m, 1H), 2.09 - 1.97 (m, 2H), 1.97 - 1.92 (m, 2H), 1.91 (s, 3H), 1.36 - 1.17 (m, 4H). EXAMPLE 17: N-((TRANS)-4-(((R)-2-(3-FLUOROPHENYL)-2-HYDROXYETHYL)AMINO)CYCLOHEXYL)METHANESULFONAMIDE Petition 870250102326, dated 07 / 11 / 2025, pp. 92 / 101 85 / 93

[0574] The title compound was prepared from tert-butyl ((trans)-4-aminocyclohexyl)carbamate according to the procedures of Example 5, using methanesulfonyl chloride in Step (a).

[0575] [α] d25= -8.9 (c 1.12, MeOH).

[0576] 1H NMR (400 MHz, CD3OD) δ 7.41 - 7.30 (m, 1H), 7.24 - 7.08 (m, 2H), 7.07 - 6.91 (m, 1H), 4.76 (dd, J = 9.2, 3.7 Hz, 1H), 3.20 (tt, J = 11.5, 4.0 Hz, 1H), 2.95 (s, 3H), 2.83 (dd, J = 12.1, 3.7 Hz, 1H), 2.73 (dd, J = 12.1, 9.2 Hz, 1H), 2.50 (tt, J = 10.8, 3.7 Hz, 1H), 2.12 - 1.91 (m, 4H), 1.46 - 1.14 (m, 4H). EXAMPLE 18: N-((TRANS)-4-(((R)-2-(5-FLUOROPYRIDIN-3YL)-2-HYDROXYETHYL)AMINO)CYCLOHEXYL)METHANESULFONAMIDE

[0577] The title compound was prepared from tert-butyl ((trans)-4-aminocyclohexyl)carbamate according to the procedures of Example 5, using methanesulfonyl chloride in Step (a) and (R)-3-fluoro-5(oxiran-2-yl)pyridine in Step (d).

[0578] [o]d25= -11.8 (c 0.84, MeOH).

[0579] 1H NMR (400 MHz, CD3OD) δ 8.47 - 8.41 (m, 1H), 8.41 - 8.33 (m, 1H), 7.73 - 7.62 (m, 1H), 4.86 - 4.82 (m, 1H), 3.20 (tt, J = 11.5, 3.9 Hz, 1H), 2.95 (s, 3H), 2.88 (dd, J = 12.1, 3.9 Hz, 1H), 2.77 (dd, J = 12.1, 8.9 Hz, 1H), 2.50 (tt, J = 10.7, 3.7 Hz, 1H), 2.11 - 1.93 (m, 4H), 1.43 - 1.15 (m, 4H). EXAMPLE 19: METHYL (R)-2-(4-((2-(3-FLUOROPHENYL)-2-HYDROXYETHYL)AMINO)-4-METHYLPIPERIDIN-1-YL)ACETATE HYDROCHLORIDE Petition 870250102326, dated 07 / 11 / 2025, pp. 93 / 101 86 / 93 . . 2HCl -((tert-butoxycarbonyl)amino)-4-methylpiperidin-1-yl)methyl acetate

[0581] Methyl bromoacetic acid ester (0.48 mL, 5.1 mmol) and K2CO3 (1.29 g, 9.3 mmol) were added to a solution of tert-butyl (4-methylpiperidin-4-yl)carbamate (1.00 g, 4.7 mmol) in DMF (10 mL) at room temperature, and the mixture was stirred at room temperature for 18 h. H2O was added and the mixture was extracted with EtOAc. The combined extracts were dried (Na2SO4) and concentrated to give the subtitle compound (0.64 g, 48%), which was used in the next step without further purification.

[0582] (b) Methyl (R)-2-(4-((2-(3-fluorophenyl)-2-hydroxyethyl)amino)-4-methylpiperidin-1-yl)acetate hydrochloride THE II l· h . 2HCl The title compound was prepared from methyl 2-(4-((tert-butoxycarbonyl)amino)-4-methylpiperidin-1-yl)acetate according to the procedures of Example 5, Steps (b) and (c). HCl (4 M in dioxane) was added to the free base in MeCN and the solids were collected, washed with Et2O and dried to give the dihydrochloride salt.

[0584] Md20-30.3 (c 0.69, MeOH).

[0585] 1H NMR (400 MHz, CD3OD) δ 7.42 (td, J = 8.0, 5.8 Hz, 1H), 7.33 - 7.24 (m, 2H), 7.12 - 7.04 (m, 1H), 5.05 (d, J = 10.2 Hz, 1H), 4.21 (s, 2H), 3.87 (s, 3H), 3.78 - 3.68 (m, 2H), 3.44 - 3.33 (m, 2H), 3.29 (d, J = 2.9 Hz, 1H), Petition 870250102326, dated 07 / 11 / 2025, pp. 94 / 101 87 / 93 3.13 (dd, J = 12.3, 10.5 Hz, 1H), 2.44 - 2.28 (m, 2H), 2.27 - 2.10 (m, 2H), 1.57 (s, 3H). EXAMPLE 20: ACETATE OF (R)-2-(4-((2-(3-FLUOROPHENYL)-2-HYDROXYETHYL)AMINO)-4-METHYLPIPERIDIN-1-YL)ACETIC ACID OH F ..AcOH

[0586] A solution of LiOH (11 mg, 0.46 mmol) in H2O (3 mL) was slowly added to a solution of (R)-2-(4-((2-(3-fluorophenyl)-2-hydroxyethyl)amino)-4-methylpiperidin-1-yl)methylacetate (225 mg, 1.21 mmol) in THF (3 mL) at room temperature, and the mixture was stirred at room temperature for 18 h. AcOH (1 mL) was added and the mixture was concentrated. The residue was dissolved in MeCN / H2O and purified by preparative HPLC (Atlantis T3, 10x100 mm, 5 μm, 0.01% AcOH in H2O:MeCN, 100:0 to 50:50) to obtain the title compound (33 mg, 96%).

[0587] Md20-17.8 (c 0.71, MeOH).

[0588] 1H NMR (400 MHz, CD3OD) δ 7.37 (td, J = 8.0, 5.8 Hz, 1H), 7.24 - 7.14 (m, 2H), 7.01 (tdd, J = 8.2, 2.7, 1.0 Hz, 1H), 4.75 (dd, J = 7.7, 4.5 Hz, 1H), 3.45 (s, 2H), 3.24 - 3.05 (m, 4H), 2.85 - 2.72 (m, 2H), 1.98 (s, 3H), 1.91 - 1.71 (m, 4H), 1.22 (s, 3H). EXAMPLE 21: HYDROCHLORIDE OF (R)-2-((4-((2-(3-FLUOROPHENYL)-2-HYDROXYETHYL)AMINO)-4-METHYLPIPERIDIN-1-YL)SULFONYL)METHYL ACETATE HCl Boc The free base of the title compound was prepared from tert-butyl (4-methylpiperidin-4-yl)carbamate according to the procedures of Example 5, using methyl 2-(chlorosulfonyl)acetate in Step (a). The hydrochloride salt was prepared by treating a solution of the free base in CHCl3 with HCl (4 M in dioxane), adding heptane, and removing the CHCl3 in a Petition 870250102326, dated 07 / 11 / 2025, pp. 95 / 101 88 / 93 argon current, collecting and drying solids.

[0590] [a]D20-17.6 (c 1.00, MeOH).

[0591] 1H NMR (400 MHz, CD3OD) δ 7.42 (td, J = 8.0, 5.8 Hz, 1H), 7.31 - 7.23 (m, 2H), 7.10 - 7.03 (m, 1H), 4.98 (dd, J = 10.3, 2.9 Hz, 1H), 4.19 (s, 2H), 3.86 - 3.79 (m, 2H), 3.78 (s, 3H), 3.27 (dd, J = 12.4, 3.0 Hz, 1H), 3.19 3.05 (m, 3H), 2.03 - 1.90 (m, 4H), 1.48 (s, 3H). EXAMPLE 22: (R)-2-((4-((2-(3-FLUOROPHENYL)-2-HYDROXYETHYL)AMINO)-4-METHYLPIPERIDIN-1-YL)SULFONYL)ACETIC ACID

[0592] The title compound was prepared from (R)-2((4-((2-(3-fluorophenyl)-2-hydroxyethyl)amino)-4-methylpiperidin-1-yl)sulfonyl)methyl acetate according to the procedure in Example 20.

[0593] [a]D20-16.7 (c 0.60, DMSO-d6 / MeOH = 1:1).

[0594] 1H NMR (400 MHz, DMSO-d6) δ 7.39 (td, J = 8.0, 6.0 Hz, 1H), 7.29 - 7.21 (m, 2H), 7.12 - 7.04 (m, 1H), 4.81 (dd, J = 9.4, 3.3 Hz, 1H), 3.95 - 3.81 (m, 2H), 3.42 - 3.34 (m, 2H), 3.18 - 3.09 (m, 2H), 3.00 - 2.90 (m, 1H), 2.74 (dd, J = 11.8, 9.5 Hz, 1H), 1.85 - 1.70 (m, 2H), 1.69 - 1.56 (m, 2H), 1.18 (s, 3H). EXAMPLE 23: (R)-2-((1-(BUTYLSULFONYL)-4-METHYLPIPERIDIN-4-YL)AMINO)-1-(3-FLUOROPHENYL)ETHANE-1-OL ACETATE

[0595] (a) (R )-4-((2-(3-fluorophenyl)-2-hydroxyethyl)amino)-4-methylpiperidine-1-carboxylate tert-Butyl Petition 870250102326, dated 07 / 11 / 2025, pp. 96 / 101 89 / 93 OH

[0596] The subtitle compound was prepared from tert-butyl 4-amino-4-methylpiperidine-1-carboxylate and (R)-2-(3-fluorophenyl)oxirane according to the procedure in Example 1, Step (g).

[0597] (b) (R )-1-(3-Fluorophenyl)-2-((4-methylpiperidin-4yl)amino)ethan-1-ol HCl (aq, 4 M, 0.39 mL, 0.16 mmol) was slowly added to a stirred solution of (R)-4-((2-(3-fluorophenyl)-2-hydroxyethyl)amino)-4-methylpiperidine-1-tert-butyl carboxylate in MeOH (1 mL) at room temperature, and the mixture was stirred at room temperature for 18 h. CH2Q2 (5 mL) and NaOH (aq, 1 M, 5 mL) were added, and the mixture was stirred at room temperature for 15 minutes. The layers were separated, and the aq phase was extracted with CH2Cl2. The combined extracts were washed with brine, dried (Na2SO4), and concentrated to give the compound of the subtitle (33 mg, 84%).

[0599] (c) (R )-2-((1-(Butylsulfonyl)-4-methylpiperidin-4yl)amino)-1-(3-fluorophenyl)ethan-1-ol 1-butanesulfonyl AcOH (8 μL, 60 μmol) was slowly added to a stirred mixture of (R)-1-(3-fluorophenyl)-2-((4-methylpiperidin-4-yl)amino)ethan-1-ol (15 mg, 60 μmol), Et3N (10 μL, 70 μmol), and MeCN (1 mL) at -18 °C. The mixture was stirred at -18 °C for 1 h. AcOH (0.1 mL) and H2O (0.5 mL) were added. The mixture was stirred at room temperature for 5 minutes, filtered (0.2 μm filter), and purified by preparative HPLC (Atlantis T3, 10x100 mm, 5 μm, 0.01% AcOH). Petition 870250102326, dated 07 / 11 / 2025, pp. 97 / 101 90 / 93 in H2O:MeCN, 100:0 to 50:50) to give the title compound (15 mg, 58%).

[0601] Md20-17.8 (c 1.40, MeOH).

[0602] RMN de1H (400 MHz, CD3OD) δ 7.38 (td, J = 8.0, 5.8 Hz, 1H), 7.27 - 7.17 (m, 2H), 7.03 (tdd, J = 8.2, 2.7, 1.0 Hz, 1H), 4.86 - 4.83 (m, 1H), 3.58 - 3.48 (m, 2H), 3.16 - 3.07 (m, 2H), 3.05 (dd, J = 12.0, 3.5 Hz, 1H), 3.02 2.97 (m, 2H), 2.92 (dd, J = 12.0, 9.4 Hz, 1H), 1.94 (s, 3H), 1.88 - 1.69 (m, 6H), 1.48 (h, J = 7.5 Hz, 2H), 1.33 (s, 3H), 0.97 (t, J = 7.4 Hz, 3H). EXEMPLO 24: ACETATO DE(R)-4-((2-(3-FLUOROFENIL)-2HIDROXIETIL)AMINO)-N,N,4-TRIMETILPIPERIDINA-1-CARBOXAMIDA

[0603] O composto do título foi preparado de acordo com os procedimentos do Exemplo 23, usando cloreto de dimetilcarbamoila na Etapa (c).

[0604] RMN de 1H (400 MHz, CD3OD) δ 7.40 (td, J = 8.1, 5.9 Hz, 1H), 7.29 - 7.19 (m, 2H), 7.08 - 7.01 (m, 1H), 4.93 - 4.90 (m, 1H), 3.63 - 3.54 (m, 2H), 3.18 - 3.03 (m, 2H), 3.02 - 2.95 (m, 2H), 2.85 (s, 6H), 1.94 (s, 3H), 1.90 1.73 (m, 4H), 1.41 (s, 3H). EXEMPLO DE FORMULAÇÃO

[0605] A pharmaceutical composition is obtained by mixing a therapeutically effective amount of a compound of formula I (such as a compound of Examples 1 to 24) with suitable excipients in suitable amounts. The resulting mixture is molded to form a tablet. Optionally, a suitable coating is applied to the tablet. BIOLOGICAL EXAMPLES

[0606] L6 myoblasts were cultured in Dulbecco's Modified Eagle Medium (DMEM) containing 1 g / L glucose supplemented with 10% fetal bovine serum, 2 mM L-Glutamine, 50 U / mL penicillin, 50 μg / mL streptomycin, and 10 mM HEPES. Cells were seeded at 1x 10⁵ cells per Petition 870250102326, dated 07 / 11 / 2025, pages 98 / 101 91 / 93 mL in 24-well plates. After reaching 90% confluence, the cells were cultured in medium containing 2% FBS for 7 days, at which point the cells differentiated into myotubes. BIOLOGICAL EXAMPLE 1: GLUCOSE UPTAKE

[0607] Differentiated L6 myotubes were stored without serum overnight in medium containing 0.5% fatty acid-free BSA and stimulated with an agonist, with a final concentration of 1x10-5M. After 1 hour and 40 minutes, the cells were washed twice with warm glucose-free medium or PBS, and another portion of agonist was added to the glucose-free medium. After 20 minutes, the cells were exposed to 50 nM of 3H-2-deoxyglucose for a further 10 minutes before being washed three times in ice-cold glucose-free medium or PBS and lysed in 400 μL / well of 0.2 M NaOH for 1 hour at 60 °C. The cell lysate was mixed with 4 mL of scintillation buffer (Emulsifier Safe, Perkin Elmer), and radioactivity was detected using a β-counter (Tri-Carb 4810TR, Perkin Elmer). The activity of each compound is compared to that of isoproterenol.If a compound exhibits activity greater than 75% of that of isoproterenol, the activity is indicated by +++; if it is between 75% and 50%, it is indicated by ++; if it is between 50% and 25%, it is indicated by +; if it is less than 25%, it is indicated by -. BIOLOGICAL EXAMPLE 2: MEASURING INTRACELLULAR cAMP LEVELS

[0608] Differentiated cells were stored with serum overnight and stimulated with an agonist, final concentration of 1x10-5M, for 15 minutes in stimulation buffer (HBSS supplemented with 1% BSA, 5 mM HEPES and 1 mM IBMX, pH 7.4). The medium was aspirated and 100 μL of 95% EtOH was added to each well of the 24-well plate and the cells were kept at 20 °C overnight. The EtOH was allowed to evaporate and 500 μL of lysis buffer (1% BSA, 5 mM HEPES and 0.3% Tween-20, pH 7.4) was added to each well. The plate was kept at -80 °C for 30 minutes and then at -20 °C until the day of detection, when the samples were thawed. Intracellular cAMP levels Petition 870250102326, dated 07 / 11 / 2025, pages 99 / 101 92 / 93 were detected using an alpha-screen cAMP kit (Perkin Elmer 6760635D). The activity of each compound is compared to that of isoproterenol. If a compound shows activity greater than 75% of that of isoproterenol, the activity is indicated by +++; if it is between 75% and 50%, it is indicated by ++; if it is between 50% and 25%, it is indicated by +; if it is less than 25%, it is indicated by -.

[0609] Using the tests described in Biological Examples 1 and 2, the following results were obtained. Example of compound # Example 1 Biological Example 2 Biological 1 ++ — 2 — — 3 +++ — 4 ++ — 5 + — 6 +++ + 7 ++ — 8 +++ + 9 + — 10 + — 11 ++ — 12 +++ — 13 ++ — 14 +++ — 15 + — 16 + — 17 ++ — 18 ++ — 19 +++ +++ 20 ++ — 21 +++ + Petition 870250102326, dated 07 / 11 / 2025, pages 100 / 101 93 / 93 Example of compound # Example 1 Biological Example 2 Biological 22 +++ — 23 +++ + 24 +++ not tested BIOLOGICAL EXAMPLE 3: GLUCOSE UPTAKE IN THE PRESENCE OF THE 32-ANTAGONIST ICI-118.551

[0610] Confirmation that glucose uptake is mediated by activation of the ε2-adrenergic receptor can be provided by observing a reduction (or absence) of glucose uptake in the presence of a β2 antagonist (ICI-118,551).

[0611] Differentiated L6 myotubes are serum-deprived overnight in a medium containing 0.5% fatty acid-free BSA and incubated with the β2-adrenergic receptor antagonist ICI-118,551 at a final concentration of 1x10⁻⁵ M for 30 minutes. The cells are stimulated with a compound of the invention at a final concentration of 1x10⁻⁵ M. After 1 hour and 40 minutes, the cells are washed twice with warm glucose-free medium or PBS, and additional portions of the compound of the invention and the antagonist are added. After 20 minutes, the cells are exposed to 50 nM of 3H₂-deoxyglucose for 10 minutes before being washed three times with chilled glucose-free medium or PBS and lysed with 0.2 M NaOH, 400 μL / well, for 1 hour at 60 °C. The cell lysate is mixed with 4 mL of scintillation buffer (Emulsifier Safe, Perkin Elmer) and the radioactivity is detected using a β-counter (Tri-Carb 4810TR, Perkin Elmer). The activity of each compound is compared to that of isoproterenol.If a compound exhibits activity greater than 75% of that of isoproterenol at 10 μM, the activity will be denoted by +++; if it is between 75 and 50%, it will be denoted by ++; if it is between 50 and 25%, it will be denoted by +; if it is less than 25%, it will be denoted by -. Petition 870250102326, dated 07 / 11 / 2025, p. 101 / 101

Claims

1 / 10 CLAIMS 1. Compound of Formula I or a pharmaceutically acceptable salt thereof, characterized in that: R1 represents H or C1-6 alkyl; each of Q1 to Q5 independently represents carbon, a heteroatom or a direct bond, such that the ring comprising Q1 to Q5 represents: a phenyl optionally substituted by one or more Y1, or a 5- or 6-membered heteroaryl optionally substituted by one or more Y2; each Y1 independently represents halo Ra1, -CN, -N3, N(Rb1)Rc1 or -ORd1; each Y2 independently represents halo Ra2, -CN, -N3, N(Rb2)Rc2 or -ORd2; ring A represents a 4- to 7-membered cycloalkyl or a 4- to 7-membered heterocycloalkyl with one or two heteroatoms selected from N or O; n represents 0 to 5; When present on a carbon atom, each Z independently represents halo, Ra3, -CN, -N3, -N(Rb3)Rc3, -ORd3, -S(O)pRe3, -S(O)qN(Rf3)Rg3, -N(Rh3)S(O)tRi3 or =O;when present on a nitrogen atom, each Z independently represents Ra3, -S(O)pRe3 or -S(O)qN(Rf3)Rg3; each Ra1 and Ra2 independently represents C1-6 alkyl optionally substituted by one or more halos; Petition 870250087969, dated 09 / 29 / 2025, p. 18 / 28 2 / 10 each Ra1 and Ra2 independently represents C1-6 alkyl optionally substituted by one or more halos; each Ra3, Re3 and Ri3 independently represents C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, each optionally substituted by one or more groups selected independently from halos and G1; Each Rb1, Rb2, Rb3, Rc1, Rc2, Rc3, Rd1, Rd2, Rd3, Rf3, Rg3 and Rh3 independently represents H, or C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, each optionally substituted by one or more groups independently selected from halo and G2;or, alternatively, any of the Rb3 and Rc3, and / or Rf3 and Rg3 may be linked together to form, together with the nitrogen atom to which they are attached, a 4- to 6-membered ring, which ring optionally contains one more heteroatom and which ring is optionally substituted by one or more halo-selected groups, C1-3 alkyl optionally substituted by one or more halos and =O; each G1 and G2 independently represents Ra4, -CN, -N3, N(Rb4)Rc4, -ORd4, -S(O)pRe4, -S(O)qN(Rf4)Rg4, -N(Rh4)S(O)rRi4 or =O; Each Ra4 independently represents a 5- or 6-membered phenyl or heteroaryl group, each optionally substituted with one or more groups selected from halo, Ra5, -CN, -N3, -N(Rb5)Rc5, -ORd5, -S(O)pRe5, -S(O)qN(Rf5)Rg5 or -N(Rh5)S(O)tRi5; each Rb4, Rc4, Rd4, Rf4, Rh4 and Rg4 independently represents H, or C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl group optionally substituted with one or more halo, -CN or =O groups;Each Re4 and Ri4 independently represents C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, each optionally substituted by one or more halos or -CN; or, alternatively, any of the Rb4 and Rc4 and / or Rf4 and Rg4 Petition 870250087969, dated 29 / 09 / 2025, p. 19 / 28 3 / 10 may be linked to form, together with the nitrogen atom to which they are attached, a 4- to 6-membered ring, which optionally contains one more heteroatom and which is optionally substituted by one or more halo-selected groups, C1-3 alkyl optionally substituted by one or more halos and =O; Each Ra5, Re5 and Ri5 independently represents C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, each optionally substituted by one or more groups selected independently from halo, C1-3 alkyl optionally substituted by one or more halo and =O;Each Rb5, Rc5, Rd5, Rf5, Rg5 and Rh5 independently represents H, or C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, each optionally substituted by one or more groups independently selected from halo, C1-3 alkyl optionally substituted by one or more halos and =O; or, alternatively, any of the Rb5 and Rc5, and / or Rf5 and Rg5 may be linked together to form, together with the nitrogen atom to which they are attached, a 4- to 6-membered ring, which ring optionally contains one more heteroatom and which is optionally substituted by one or more groups independently selected from halo, C1-3 alkyl optionally substituted by one or more halos and =O; each p independently represents 0, 1 or 2; each q independently represents 1 or 2; each r independently represents 1 or 2;and each t independently represents 1 or 2, with the exceptions (A) to (C) that the compound of formula I is not any of the following: (A) 4-[[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethyl]amino]cyclohexan-1-ol; (B) (aR)-a-[[(3-Methylcyclobutyl)amino]methyl]benzenemethanol; Petition 870250087969, dated 29 / 09 / 2025, page 20 / 28 4 / 10 (aS)-a-[[(3-Methylcyclobutyl)amino]methyl]benzenemethanol; a-[[(3-Methylcyclobutyl)amino]methyl]benzenemethanol; a-[[(3-Aminocyclobutyl)amino]methyl]benzenemethanol; (aR)-a-[[(3-hydroxycyclobutyl)amino]methyl]benzenemethanol; (aS)-a-[[(3-hydroxycyclobutyl)amino]methyl]benzenemethanol; a-[[(3-hydroxycyclobutyl)amino]methyl]benzenemethanol; a-[[(3-Methylcyclobutyl)amino]methyl]-3-pyridinamethanol; a-[[(3-Methylcyclobutyl)amino]methyl]-4-pyridinamethanol; a-[[(4-Methylcyclohexyl)amino]methyl]benzenemethanol; (aS)-a-[[(3-Methylcyclopentyl)amino]methyl]benzenemethanol; (aR)-a-[[(3-Methylcyclopentyl)amino]methyl]benzenemethanol; a-[[(trans-4-Methylcyclohexyl)amino]methyl]benzenemethanol;a-[[(3-Aminocyclopentyl)amino]methyl]benzenometanol; a-[[(3-Methylcyclopentyl)amino]methyl]benzenometanol; a-[[(3-Methylcyclohexyl)amino]methyl]benzenometanol; a-[[(3-Aminocyclohexyl)amino]methyl]benzenometanol; a-[[(4-Aminocyclohexyl)amino]methyl]benzenometanol; a-[[(3-Fluorocyclobutyl)amino]methyl]benzenometanol; a-[[(3-Methylcyclobutyl)amino]methyl]-2-pyridinenametanol; a-[[(3-hydroxycyclobutyl)amino]methyl]-3-pyridinenametanol; (aR)-a-[[(3-Fluorocyclobutyl)amino]methyl]benzenometanol; a-[[(4-Methylcycloheptyl)amino]methyl]benzenometanol; (aR)-a-[[(1-Methyl-3-azetidinyl)amino]methyl]benzenometanol; a-[[(1-Methyl-3-azetidinyl)amino]methyl]benzenometanol; (aS)-a-[[(1-Methyl-3-azetidinyl)amino]methyl]benzenometanol; a-[[(4-Hydroxycyclohexyl)amino]methyl]benzenometanol; a-[[(3-Methylcyclopentyl)amino]methyl]-3-pyridinametanol; a-[[(3-Methylcyclopentyl)amino]methyl]-4-pyridinametanol; a-[[(3-hydroxycyclobutyl)amino]methyl]-2-pyridinametanol; a-[[(4-Methylcyclo-hexyl)amino]methyl]-4-pyridinamethanol;Petition 870250087969, 09 / 29 / 2025, pág. 21 / 28 5 / 10 a-[[(3-Methylcyclo-hexyl)amino]methyl]-4-pyridinemethanol; (aR)-a-[[(1-Methyl-3-pyrrolidinyl)amino]methyl]benzenomethanol; (aS)-a-[[(1-Methyl-3-pyrrolidinyl)amino]methyl]benzenomethanol; a-[[(1-Methyl-3-pyrrolidinyl)amino]methyl]benzenomethanol; 5-[(2-hidroxi-2-phenylethyl)amino]cyclooctanol; a-[[(3-Fluorocyclobutyl)amino]methyl]-3-pyridinemethanol; a-[[(1-Methyl-3-piperidinyl)amino]methyl]benzenometanol; a-[[(1-Methyl-3-azetidinyl)amino]methyl]-3-pyridinamethanol; a-[[(Hexahidro-1 -methyl-1H-azepin-4yl)amino]methyl]benzenometanol; a-[[(3-Fluorocyclobutyl)amino]methyl]-2-pyridinamethanol; a-[[(1-Methyl-3-pyrrolidinyl)amino]methyl]-4-pyridinamethanol; a-[[(1-Methyl-3-pyrrolidinyl)amino]methyl]-3-pyridinamethanol; a-[[(1-Methyl-4-piperidinyl)amino]methyl]benzenometanol hydrochloride; a-[[(1-Methyl-3-azetidinyl)amino]methyl]-2-pyridinemethanol;(C) a-[[(1-Methyl-4-piperidinyl)amino]methyl]benzenemethanol, 2-((1-benzylpiperidin-4-yl)amino)-1 -phenylethanol, 4-(1 -hydroxy-2-((1 -methylpiperidin-4-yl)amino)ethyl)phenol, 4-(2-((1-benzylpiperidin-4-yl)amino)-1 -hydroxyethyl)phenol, 4-(2-((1-butylpiperidin-4-yl)amino)-1 -hydroxyethyl)phenol, 3-(2-((1-butylpiperidin-4-yl)amino)-1 -hydroxyethyl)phenol, 4-(1 -hydroxy-2-((1 -(2-methoxyethyl)piperidin-4-yl)amino)ethyl)phenol, or 4-(1 -hydroxy-2-((1 -phenethylpiperidin-4-yl)amino)ethyl)phenol.; 2. Compound according to claim 1, characterized in that it is with the additional reservations (D) to (M) that the compound of formula I is none of the following: (D) Petition 870250087969, dated 29 / 09 / 2025, p. 22 / 28 6 / 10 ?HHJ? OH 9H H xyy ?HH hct^ <χ^|<ζιχ^'ΒΓ / yx çxx OH Cl} ç / Ao çr°O 0H OH °HH 91 9H H Ό # W / > wl ?H Η °H h ΗΟγ^^ / Ν-χ^\ Petition 870250087969, from 29 / 09 / 2025, page 23 / 28 7 / 10 3. Compound, according to claim 1 or 2, characterized in that the ring comprising Q1 to Q3 represents: phenyl optionally substituted by one or more Y1; or pyridyl optionally substituted by one or more Y2.

4. A compound, according to any of the preceding claims, characterized in that each Y1 independently represents Ra1, halo, or -CN.

5. A compound, according to any of the preceding claims in Petition 870250087969, dated 09 / 29 / 2025, pp. 24 / 28 8 / 10, characterized in that each Y2 independently represents Ra2, halo, or -CN.

6. A compound, according to any of the preceding claims, characterized in that each Y1 and Y2 represents F.

7. A compound, according to any of the preceding claims, characterized in that, when present on a carbon atom, each Z independently represents halo, Ra3, -CN, -N(Rb3)Rc3, -ORd3 or -N(Rh3)S(O)tRi3.

8. A compound, according to any of the preceding claims, characterized in that when present on a carbon atom, each Z independently represents Ra3, -N(Rb3)Rc3, -ORd3 or -N(Rh3)S(O)tRi3, as Ra3.

9. A compound, according to any of the preceding claims, characterized in that t represents 2.

10. A compound, according to any of the preceding claims, characterized in that n represents 1.

11. A compound, according to any of the preceding claims, characterized in that the compound of formula I is a compound of formula IX m2 |X wherein Q1 to Q5, R1, n and Z are as defined in any of the preceding claims; X represents C or N; m1 and m2 independently represent 0 to 2.

12. Compound according to claim 11, characterized in that the compound of formula IX is a compound of formula IE Petition 870250087969, dated 09 / 29 / 2025, p. 25 / 28 9 / 10 where the ring comprising Q1 to Q5, R1 and Z are as defined in any of the preceding claims, and X is as defined in claim 11.

13. Compound, according to any one of claims 1 to 12, characterized in that it is for use in medicine.

14. Pharmaceutical composition characterized in that it comprises a compound, as defined in any one of claims 1 to 12, and optionally one or more pharmaceutically acceptable adjuvants, diluents and / or carriers.

15. A compound, according to any one of claims 1 to 12, characterized in that it is for use in the treatment of hyperglycemia or a disorder that has hyperglycemia as a particular characteristic.

16. Use of a compound, as defined in any one of claims 1 to 12, characterized in that it is for the manufacture of a medicament for the treatment of hyperglycemia or a disorder that has hyperglycemia as a particular characteristic.

17. A method for treating hyperglycemia or a disorder characterized by hyperglycemia, comprising administering to a patient in need thereof a therapeutically effective amount of a compound, as defined in any one of claims 1 to 12.

18. Compound for use, method or application, according to any of claims 15 to 17, characterized in that hyperglycemia or the disorder characterized by hyperglycemia is, or is characterized by the patient having severe insulin resistance.

19. Compound for use, method or application, according to any of claims 15 to 18, characterized in that the disorder having Petition 870250087969, dated 09 / 29 / 2025, page 26 / 28 10 / 10 as its particularity is selected from the group consisting of type 2 diabetes, Rabson-Mendenhall syndrome, Donohue syndrome (leprechaunism), type A and type B insulin resistance syndromes, HAIR-AN syndromes (hyperandrogenism, insulin resistance and acanthosis nigricans), pseudoacromegaly and lipodystrophy.

20. A compound, according to any one of claims 1 to 12, characterized in that it is for use in the treatment of non-alcoholic fatty liver disease.

21. Use of a compound, according to any one of claims 1 to 12, characterized in that it is used in the manufacture of a medicament for the treatment or prevention of non-alcoholic fatty liver disease.

22. A method for treating or preventing non-alcoholic fatty liver disease, as defined in, characterized in that it comprises administering to a patient in need thereof a therapeutically effective amount of a compound, as defined in any one of claims 1 to 12.

23. A compound, according to any one of claims 1 to 12, characterized in that it is for use in the treatment of a disease or disorder whose treatment is mediated by the activation of the β2 adrenergic receptor.

24. Use of a compound, according to any one of claims 1 to 12, characterized in that it is in the manufacture of a medicament for use in the treatment of a disease or disorder whose treatment is mediated by the activation of the β2 adrenergic receptor.

25. A method for treating a disease or disorder whose treatment is mediated by the activation of the β2 adrenergic receptor, characterized in that it comprises administering to a patient in need thereof a therapeutically effective amount of a compound, as defined in any one of claims 1 to 12. Petition 870250087969, dated 09 / 29 / 2025, pp. 27 / 28