COMPOUND, PHARMACEUTICAL COMPOSITION, AND METHOD FOR PRODUCING AN ANTI-INVASIVE EFFECT BY CONTAINING AND / OR TREATING SOLID TUMOR DISEASE

Abstract

A compound of Formula (I):or a pharmaceutically acceptable salt thereof, wherein: X1 is CH or N; p is 0, 1 or 2; where: each R1 is a substituent on any C atom and is independently selected from F, Cl, C1-3alkyl and C1-3 alkoxy, wherein said C1-3alkyl and C1-3alkoxy may be independently optionally substituted by one or more F; RN is selected from H and Me; n is 0, 1 or 2; m is 0 or 1; Q1 is CH or N; when n & m are both other than 0, Q2 is CH or N; when n & m are both 0, Q2 is CH; when n is 0 or 1, Q3 is CH; when n is 2 and Q2 is N, Q3 is CH; when n is 2 and Q2 is CH, Q3 is CH or O; R2a and R2b are substituents on the same or different C atoms other than at Q1 or Q2, each independently selected from H, F and C1-3alkyl, or R2a & R2b together form a -(CH2)r- group where r is 1, 2 or 3; Q4 is a single bond or -NR4C(=O); R4 is H or Me; 0, 1 or 2 of Y1, Y2, Y3, Y4 & Y5 is / are N, and are otherwise C; each R3 is a substituent on any C atom at Y1, Y2, Y3, Y4 & Y5, and is independently selected from F, Cl, CN, C1-3,alkyl and C1-3 alkoxy. wherein said C1-3 alkyl and C1-3 alkoxy may be independently optionally substituted by one or more F; q is 0, 1 or 2; wherein Linker is attached at any available C atom at Y4 & Y5; Linker is a saturated or a partially or fully unsaturated framework comprising C and H atoms and at least one heteroatom, wherein said framework has end points of attachment 'a' and 'b' and a length of from 5 to 26 atoms between 'a' and 'b'; wherein said framework may include one or more straight and / or branched chains and / or rings and is optionally substituted on any available C atom(s) by one or more F; and W is an E3 ubiquitin ligase cereblon binder unit.

Description

COMPOUND, PHARMACEUTICAL COMPOSITION, AND METHOD FOR PRODUCING AN ANTI-INVASIVE EFFECT BY CONTAINING AND / OR TREATING SOLID TUMOR DISEASE. RELATED APPLICATIONS

[001] This application claims priority over US Provisional Patent Application No. 63 / 489,528, filed March 10, 2023, the disclosure of which is incorporated herein in its entirety. FIELD

[002] This descriptive report refers to certain compounds of Proteolysis Targeting Chimera (PROTAC) and, at a minimum, its ability to degrade the Androgen Receptor (AR), and therefore its use for the treatment of androgen receptor-dependent diseases or disorders in mammals. The degradation of androgen receptors can provide, for example, an antitumor effect, and consequently, this descriptive report refers in part to the use of these compounds for cancer treatment and to pharmaceutical compositions containing them. It also refers to intermediate compounds that may be useful in the preparation of these PROTACs. BACKGROUND

[003] Traditional small molecule drugs bind reversibly (or sometimes irreversibly) to a target protein as a means of modulating a particular biological activity. In contrast, PROTACs bind to their target proteins but then cause the target protein to degrade. Having achieved this effect, the PROTAC is, in theory, capable of repeating this process with another target protein. Consequently, unlike traditional small molecule inhibitors, the degradation mechanism triggered by PROTAC can, in theory, operate in a substoichiometric manner – meaning that more modest exposures of a PROTAC compound can still achieve a desired level of efficacy in vivo. Petition 870250080967, dated 09 / 09 / 2025, page 11 / 523 / 482 In practice, this may mean that the degradation power (DC50 and Dmax) of a PROTAC may have an enhanced effect compared to that reflected solely by its binding affinity.

[004] At a simplistic level, PROTAC molecules are often described as having three parts - (1) a part that is able to bind to the target protein to be degraded, (2) a second part that is able to bind to an E3 ubiquitin ligase and, finally, a linker that connects (1) and (2) together.

[005] In use, PROTAC binds to the target protein and E3 ubiquitin ligase simultaneously to form a ternary complex. The E3 ligase then recruits an E2 conjugating enzyme to the ternary complex, which ubiquitinates the target protein. This has the effect of marking the target protein for degradation by the cell's proteasome machinery. A PROTAC can then dissociate from the target protein and initiate another cycle of this process catalytically. Meanwhile, the ubiquitinated target proteins are recognized and degraded by the cell's proteasome machinery.

[006] This PROTAC-mediated approach may be valuable as a treatment method for certain diseases where targeted degradation of specific body proteins may be beneficial, for example, in cancer treatment. One such cancer-related target is the androgen receptor.

[007] The androgen receptor (AR) belongs to the group of nuclear steroid hormone receptors and is a ligand-dependent transcription factor that controls the expression of a range of genes involved in the growth and survival of prostate cells. The AR is composed of four distinct domains: the amino-terminal domain (NTD - N-terminal domain), the DNA-binding domain (DBD - DNA binding domain), a hinge region that allows the N and C ends to interact, and a C-terminal ligand-binding domain (LBD - ligand binding domain). The Petition 870250080967, dated 09 / 09 / 2025, page 12 / 523 / 482. Androgens, such as testosterone and its derivative dihydrotestosterone (DHT), bind to the ligand-binding domain of AR, which releases AR chaperone proteins, allowing AR to dimerize and translocate from the cytoplasm to the nucleus. In the nucleus, receptor dimers bind to androgen response elements (AREs) in the promoters of androgen-responsive genes, such as PSA and FKBP5. The AR signaling pathway plays a role in normal prostate development, and male sexual differentiation does not occur in the absence of androgens or without a functional AR.

[008] The relationship between androgens and prostate cancer was first discovered in a seminal study by Huggins and Hodges in 1941, and subsequent work has shown that androgen deprivation therapy is highly effective in treating recurrent prostate cancer. However, despite initially satisfactory responses, most tumor cells adapt to low androgen levels, and patients relapse within a few years, developing a diseased state known as castrate-resistant prostate cancer (CRPC). Several second-generation antiandrogens have been approved by the US FDA for the treatment of CRPC. These include enzalutamide, apalutamide, and darolutamide, which compete with androgens for binding to the ligand-binding domain. In addition to antagonizing the AR, preventing its activation, they also inhibit nuclear translocation and DNA binding, effectively disrupting AR signaling.In contrast, abiraterone acetate is an inhibitor of androgen biosynthesis that targets the cytochrome p450 (CYP17) enzyme 17R-hydroxylase-17,20-lyase. Testosterone is processed in the testes and adrenal glands by CYP17, and therefore, inhibition of this enzyme inhibits prostate tumor growth by decreasing circulating androgen levels. Petition 870250080967, dated 09 / 09 / 2025, page 13 / 523 / 482

[009] Although the aforementioned drugs significantly prolong the survival of patients with advanced prostate cancer, they are not curative, and resistance inevitably occurs. However, it is evident that the AR remains central to CRPC progression, meaning there is still a need to develop alternative AR inhibitors. Several resistance mechanisms have been identified, including AR amplification, mutation, or the generation of splice variants lacking the ligand-binding domain. Mutations in the ligand-binding domain, for example F877L or L702H, can convert antagonists into agonists or allow the receptor to utilize alternative steroid hormones, such as glucocorticoids or progesterone. Agents that degrade the AR, removing it from the cell, could therefore help combat these forms of resistance.Thus, AR PROTACs, which bind to the ligand-binding domain of the androgen receptor and simultaneously recruit an E3 ligase, such as cereblon, leading to ubiquitination and degradation of AR through the proteasome, could offer therapeutic benefit to patients with prostate cancer, particularly metastatic CRPC. AR PROTACs may also be useful against AR+ breast cancer.

[0010] Given that the aforementioned resistance mutations that can occur in the ligand-binding domain may limit the effectiveness of known CRPC treatments, it would be beneficial to develop AR-degrading PROTACs that not only target wild-type AR but are also effective in degrading clinically relevant mutated forms of AR.

[0011] Whatever target protein binding unit (1) is used at one end of a PROTAC binding unit, a fundamental element that must always be present at the other end of a PROTAC molecule is a unit (2) that helps direct the targeting of the target protein for degradation, for example, an E3 binding unit. Petition 870250080967, dated 09 / 09 / 2025, p. 14 / 523 / 482 ubiquitin ligase cereblon. Scientific efforts have already provided a number of these E3 ubiquitin ligase cereblon binding units, and other examples are demonstrated below by the present researchers.

[0012] Document no. WO2018 / 071606 describes certain PROTAC compounds considered to be AR degraders.

[0013] As with traditional small molecule binders and PROTACs, there is always the issue of off-target activity in vivo, which can be important to avoid in the development of safe and effective drug treatments. In other words, a given binding unit may be very potent against the intended target, but if it is inadvertently potent against other unintended biological targets in the human body, it may cause unacceptable toxicities, side effects, and so on.

[0014] Therefore, it is an ongoing challenge to develop potent molecules for pharmaceutical use that are also adequately selective – that is, avoiding the inhibition / binding / degradation of unintended biological targets in vivo.

[0015] For example, the present researchers surprisingly found that certain compounds in this descriptive report show beneficial selectivity that is expected to avoid or reduce the risk of mitotoxicity in vivo.

[0016] As part of the development of current and future PROTAC drug treatments for medicinal use (e.g., cancer), there is still a need to develop androgen receptor PROTAC compounds that have a combination of beneficial / enhanced properties. As mentioned above, the development of PROTACs that target wild-type AR and one or more clinically relevant mutated forms of AR is an example of this combination effect. Petition 870250080967, dated 09 / 09 / 2025, page 15 / 523 / 482

[0017] Furthermore, there is a need to develop androgen receptor binding units that can be incorporated into a PROTAC, regardless of which E3 ubiquitin ligase cereblon binding unit is selected for use at the other end of the molecule.

[0018] Other properties of interest during pharmaceutical discovery and the development of these PROTACs may be related to selectivity profile, absorption / bioavailability, distribution, metabolism, elimination, toxicity and side effect profile, stability, manufacturability, and so on. SUMMARY

[0019] The compounds in this descriptive report provide, at a minimum, potent AR-binding units suitable for incorporation into PROTAC compounds and PROTAC compounds containing these AR-binding units together with an E3 ubiquitin ligase cereblon binder unit at the other end of the PROTAC molecule. Certain AR-binding units are advantageously configured to degrade not only wild-type AR but also one or more clinically relevant mutant forms of AR, for example L702H. Certain PROTAC compounds in this descriptive report also have a surprisingly beneficial combination of properties, for example, related to AR degradation and selectivity / safety profile in combination.

[0020] This descriptive report refers to the aforementioned AR-binding units and to PROTAC compounds (and pharmaceutically acceptable salts thereof) incorporating these AR-binding units together with an E3 ubiquitin ligase cereblon binder unit (the two units being linked by a ligand).

[0021] This descriptive report also refers to pharmaceutical compositions containing these PROTACs (and pharmaceutically acceptable salts thereof) and their use in methods of treatment in the human body or Petition 870250080967, dated 09 / 09 / 2025, p. 16 / 523 / 482 animal, for example, in the treatment or prevention of cancer. This descriptive report also refers to processes and intermediate compounds (and salts thereof) involved in the preparation of said PROTACs.

[0022] According to the first aspect of this descriptive report, a compound of formula (I) is provided: (I) or a pharmaceutically acceptable salt thereof, provided that: X1 is CH or N; p is 0, 1, or 2; in which: each R1 is a substituent on any C atom and is independently selected from F, Cl, C1-3 alkyl and C1-3 alkoxy, wherein said C1-3 alkyl and C1-3 alkoxy may be independently and optionally substituted by one or more F; Rné selected from between H and Me; n is 0, 1, or 2; m is 0 or 1; Q1 is CH or N; when neither of them is different from 0, Q2 is CH or N; when neither of them is 0, Q2 is CH; when n is 0 or 1, Q3 is CH; when n is 2 and Q2 is N, Q3 is CH; when n is 2 and Q2 is CH, Q3 is CH or O; Petition 870250080967, dated 09 / 09 / 2025, page 17 / 523 / 482 R2a and R2b are substituents on the same or different C atoms, except on Q1 or Q2, each independently selected from H, F and C1-3 alkyl, or R2a and R2b together form a -(CH2)r- group, wherein r is 1, 2 or 3; Q4 is a simple bond or -NR4C(=O); R4é H ou Me; 0, 1, or 2 among Y1, Y2, Y3, Y4, and Y5 are N, and otherwise, they are C; each R3 is a substituent on any C atom in Y1, Y2, Y3, Y4 and Y5, and is / are independently selected from F, Cl, CN, C13 alkyl and C13 alkoxy, wherein said C13 alkyl and C13 alkoxy may be independently and optionally substituted by one or more F; q is 0, 1, or 2; whereby the ligand is bonded to any available C atom in Y4 and Y5; The ligand is a saturated or partially or completely unsaturated structure comprising C and H atoms and at least one heteroatom, said structure having terminal bonding points 'a' and 'b' and a minimum length of 5 to 26 atoms between 'a' and 'b'; said structure may include one or more linear and / or branched chains and / or rings and is optionally replaced at any available C atom(s) by one or more F atoms; and W is a binding unit of E3 ubiquitin ligase cereblon.

[0023] This descriptive report also describes, in part, a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient. Petition 870250080967, dated 09 / 09 / 2025, p. 18 / 523 / 482

[0024] This descriptive report also describes, in part, a compound of formula (I), or a pharmaceutically acceptable salt thereof, for use in therapy.

[0025] This descriptive report also describes, in part, a compound of formula (I), or a pharmaceutically acceptable salt thereof, for use in the treatment of cancer.

[0026] This descriptive report also describes, in part, a method for treating cancer in a warm-blooded animal in need of such treatment, comprising administering to the warm-blooded animal a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof.

[0027] As shown in the experimental section below, the present researchers not only developed a range of beneficial AR-binding units, but also gained an understanding of where these binding units can incorporate a ligand (leading to an E3 ubiquitin ligase cereblon binding unit) without interfering with their AR-binding capacity. Consequently, the present researchers understand that when incorporating their AR-binding units into a PROTAC, the ligand of said PROTAC should not bind to the left or center rings in formula (I) shown above, but can bind appropriately to the specified position in the right ring in the compound of formula (I) as shown herein.

[0028] Therefore, in a further aspect of this descriptive report, a PROTAC compound or a pharmaceutically acceptable salt thereof is provided, containing an E3 ubiquitin ligase cereblon binding unit and an AR binding unit of formula (Ia): Petition 870250080967, dated 09 / 09 / 2025, p. 19 / 523 / 482 c (Ia) where R1, p, X1, RN, n, m, R2a, R2b, Q1, Q2, Q3, Q4, Y1, Y2, Y3, Y4, Y5, R3 and q can assume any of the values ​​defined here for each of these integers, respectively.

[0029] To avoid doubt, ^c in formula (Ia) indicates a connection point via a single covalent bond to the rest of the PROTAC compound.

[0030] In one embodiment, a PROTAC compound or a pharmaceutically acceptable salt thereof is provided, containing an E3 ubiquitin ligase cereblon binder unit linked to an AR-binding unit of formula (Ia), as described herein.

[0031] As described herein, the linkage between an E3 ubiquitin ligase cereblon binding unit and an AR-linking unit of formula (Ia) as shown above may have a length corresponding to the length of a linear chain of 5 to 26 atoms, said atoms being linked by single covalent bonds and each selected from carbon or a heteroatom (i.e., O, N or S).

[0032] As described herein, the linkage between an E3 ubiquitin ligase cereblon binding unit and an AR-linking unit of formula (Ia) as shown above may have a length corresponding to the length of a linear chain of 5 to 14 atoms, said atoms being linked by single covalent bonds and each selected from carbon or a heteroatom (i.e., O, N or S). Petition 870250080967, dated 09 / 09 / 2025, p. 20 / 523 / 482

[0033] In one embodiment, the linkage between an E3 ubiquitin ligase cereblon binding unit and an AR-binding unit of formula (Ia) as shown above may have a length corresponding to the length of a linear chain of 5 to 26 atoms, said atoms being linked by single covalent bonds and each selected from C, N or O.

[0034] In one embodiment, the linkage between an E3 ubiquitin ligase cereblon binding unit and an AR-linking unit of formula (Ia) as shown above may have a length corresponding to the length of a linear chain of 5 to 14 atoms, said atoms being linked by single covalent bonds and each selected from C, N or O.

[0035] It should be understood that, although a bond length corresponds to the length of [certain atoms in a chain], this should not be interpreted as limiting said bond to said atoms and, for example, the sulfur atom(s) may also be present in the bond, even if the S atoms are not included in the length descriptor.

[0036] In a further aspect of the descriptive report, an androgen receptor binding unit of formula (Ia), as described herein, is provided for use in a PROTAC compound (or pharmaceutically acceptable salt thereof) which also contains an E3 ubiquitin ligase cereblon binding unit.

[0037] In a further aspect of the descriptive report, an androgen receptor binding unit of formula (Ia), as described herein, is provided for use in a PROTAC compound (or pharmaceutically acceptable salt thereof) that is linked to an E3 ubiquitin ligase cereblon binder unit. Petition 870250080967, dated 09 / 09 / 2025, p. 21 / 523 / 482

[0038] Consequently, an androgen receptor binding unit of formula (Ia), as described herein, is provided for use in a PROTAC compound (or pharmaceutically acceptable salt thereof) wherein said PROTAC compound also contains an E3 ubiquitin ligase cereblon binding unit.

[0039] Consequently, an androgen receptor binding unit of formula (Ia), as described herein, is provided for use in a PROTAC compound (or pharmaceutically acceptable salt thereof) wherein said PROTAC compound also contains an E3 ubiquitin ligase cereblon binding unit that is linked to said androgen receptor binding unit.

[0040] Consequently, an androgen receptor binding unit of formula (Ia), as described herein, is provided for incorporation into a PROTAC compound (or a pharmaceutically acceptable salt thereof) wherein said PROTAC compound also contains an E3 ubiquitin ligase cereblon binding unit.

[0041] Consequently, an androgen receptor binding unit of formula (Ia), as described herein, is provided for incorporation into a PROTAC compound (or a pharmaceutically acceptable salt thereof) wherein said PROTAC compound also contains an E3 ubiquitin ligase cereblon binder unit that is linked to said androgen receptor binding unit.

[0042] Therefore, an androgen receptor binding unit of formula (Ia), as described herein, is provided, contained in a PROTAC compound (or a pharmaceutically acceptable salt thereof) wherein said PROTAC compound also contains an E3 ubiquitin ligase cereblon binding unit.

[0043] Therefore, an androgen receptor binding unit of formula (Ia) is provided, as described herein, contained in a compound Petition 870250080967, dated 09 / 09 / 2025, p. 22 / 523 / 482 PROTAC (or a pharmaceutically acceptable salt thereof) wherein said PROTAC compound also contains an E3 ubiquitin ligase cereblon binding unit that is linked to said androgen receptor binding unit.

[0044] In one embodiment, the linkage between the androgen receptor binding unit of formula (Ia) [as described above] and an E3 ubiquitin ligase cereblon binding unit is a Ligand as defined according to any embodiment or claim herein, wherein the binding site shown in formula (Ia) above connects to the binding site 'a' in any Ligand as defined herein. DESCRIPTION OF ILLUSTRATIVE MODALITIES

[0045] Many aspects of this disclosure are detailed throughout the descriptive report and will be evident to a reader skilled in the art.

[0046] A pharmaceutically acceptable salt of a compound of formula (I) or a PROTAC compound described herein may be, for example, an acid addition salt when said compound contains a basic functional group, such as an amine. An acid addition salt may be formed using an inorganic acid or an organic acid. A pharmaceutically acceptable salt of said compound may be, for example, a basic addition salt when said compound contains an acidic functional group, such as a carboxylic acid. An acid addition salt may be formed using an inorganic base or an organic base. Pharmaceutically acceptable salt is used to specify that the salt is suitable for use in the human or animal body. A list of examples of pharmaceutically acceptable salts may be found in the Handbook of Pharmaceutical Salts: Properties, Selection and Use, PH Stahl and CG Wermuth, editors, Weinheim / Zurich:Wiley-VCH / VHCA, 2002.A pharmaceutically acceptable salt of a compound of formula (I) or a PROTAC compound includes those salts that may be formed in the human or animal body after administration of said compound to said human or animal body. Petition 870250080967, dated 09 / 09 / 2025, p. 23 / 523 14 / 482

[0047] As used herein, the term alkyl includes linear, branched, and cyclic alkyl groups and combinations thereof having the specified number of carbon atoms. Therefore, C1-alkyl includes methyl, ethyl, n-propyl, isopropyl, and cyclopropyl; and C1-alkyl would include (4-isopropylcyclohexyl)methyl. The same principles apply to the term alkoxy. Similarly, as used herein, the term alkoxy includes linear, branched, and / or cyclic alkoxy groups with the specified number of carbon atoms. Therefore, C1-alkoxy includes methoxy, ethoxy, n-propoxy, isopropoxy, and cyclopropoxy.

[0048] In this descriptive report, chemical abbreviations familiar to those skilled in the art may be used, including, for example, Me = methyl, Et = ethyl, Pr = propyl, Bu = butyl, and Ph = phenyl.

[0049] When the term optionally is used, it is intended that the subsequent feature may or may not occur. Thus, the use of the term optionally includes cases where the feature is present and also cases where the feature is not present. For example, methyl optionally replaced by one or more F includes -CEE, -CH2F, -CHF2 and -CF3.

[0050] The term substituted means that one or more hydrogens on the designated atom or group are replaced by the indicated substituent(s), provided that any atom(s) containing such substituent(s) retain(s) their permitted valence, wherein one skilled in the art understands that the standard valences of carbon, nitrogen, and oxygen are 4, 3, and 2, respectively. Therefore, substituted on any available C atom(s) should be understood as meaning that the substituent(s) is / are limited in its / their position(s) (and / or potentially in its / their number) according to the existence of remaining hydrogen atoms on the designated atom or group that could be replaced by said substituent(s).

[0051] The dashed links included in Z, -ττττ:, indicate the possibility that the link may, in each case, be a covalent bond. Petition 870250080967, dated 09 / 09 / 2025, p. 24 / 523 / 482 single or a double covalent bond - according to the atom (or group of atoms) present in each of the positions XE, XF, XG, XH2 and XJ. One skilled in the art understands that the standard valences of carbon, nitrogen and oxygen are as mentioned above and, in this way, can understand whether each dashed bond should be interpreted as a single bond or a double bond in any given group Z in the compound of formula (I). The same applies to the positions XE2, XF2, XG2, XH2 and XJ2 in ZA.

[0052] The term adjacent or adjacent position - for example, in reference to XG, XHe XJ of Z refers to the next closest position in the molecular chain / ring system. Consequently, in the context of Z: XG and XHe are in adjacent positions to each other, XHe and XJ are also in adjacent positions to each other, but XG is not in adjacent positions to XJ.

[0053] The term saturated means that the atoms of the specified structure or group are linked only by single covalent bonds. Consequently, the term unsaturated means that the specified structure or group contains double and / or triple covalent bonds. Examples of unsaturated molecular fragments that may be present within a partially or completely unsaturated group or structure are C=C, C=N, C=O, N=N, C=C or C=N in cases where nitrogen and oxygen heteroatoms are allowed / present, and may also include S=O in cases where sulfur heteroatoms are also allowed / present.

[0054] It should be understood that heteroatom can represent an oxygen, nitrogen or sulfur atom, except where explicitly limited in a given context.

[0055] The term minimum length of [...] atoms between 'a' and 'b' refers to the shortest chain of atoms in the chain between 'a' and 'b'. Therefore, if the chain consists of -CH2CH2CH2-, the number of atoms in the chain is 3 (hydrogen atoms are considered as not being in the chain). Alternatively, if the chain consists of 1,3-phenylene, where the route is shorter Petition 870250080967, dated 09 / 09 / 2025, p. 25 / 523 / 482: If the short route around the phenyl ring contains 3 C atoms and the long route around the phenyl ring contains 5 C atoms, the minimum length of this chain would be counted as 3 atoms.

[0056] It should be understood that the bonding points 'a' and 'b' each represent single covalent bonds to the relevant adjacent groups / atoms.

[0057] It should be understood that direct linking is interchangeable with simple linking.

[0058] It should be understood that in this descriptive report heterocyclic rings or groups may include single rings, fused rings, spirocyclic rings and bridging rings.

[0059] With reference to the Ligand, as described herein, it should be understood that branching, when present, may be present in a chain (even a chain of 1 atom in length) and / or in a ring. Those skilled in the art would generally interpret it this way, but to avoid confusion, it should be understood that branching that inherently occurs in order to form a ring is not considered branching in the context of the Ligand embodiments described herein. It should be understood that said branching may occur on the same or different atoms of the Ligand structure. For example, it is possible to have two -O branches on a sulfur heteroatom to form an SO2 group within the Ligand structure. Ligand No. 22 described below is an example where there is a branch (-Me) originating from a chain within the Ligand.

[0060] It should be further understood that 'branching' (and definitions for branching given here) refers to branching off from the main chain of atoms between 'a' and 'b', leading to a 'terminal point' in the molecular structure.

[0061] In this descriptive report, it should be understood that the connection point of a given group to some other group (through a connection) Petition 870250080967, dated 09 / 09 / 2025, p. 26 / 523 / 482 simple covalent bond) can be represented by a line that meets a bond substantially at right angles to said bond, for example, as shown on the right-hand side of formula (Ia) here and, for example, at each end of Ligands 1 to 46 shown below.

[0062] In this descriptive report, when 0, 1 or 2 of Xa, Xb, Xc, Xd, XE and XF is / are N, wherein XE and XF are not both N and, otherwise, are C - some of the C atoms should be understood as implicitly possessing a hydrogen atom, when necessary, in order to satisfy the standard valence (4) for carbon atoms. Those skilled in the art will understand that this H atom cannot be present in a C in XE or XF or in a C in Xa, Xb, Xc or Xd when a substituent or a ligand is attached to said carbon. The same principle applies with respect to X1, X2, X3, X4 (and with X5, X6, X7 and X8 when present), and also with Y1, Y2, Y3 and Y4. The same applies to Xa2, XB2, XC2, XD2, XE2, XF2, XG2, XH2 and XJ2.

[0063] In this descriptive report, a reference to a secondary or tertiary amine is intended to have the normal meaning in the art and, therefore, a nitrogen atom that is part of an amide group or a sulfonamide group, for example, should not be considered as a secondary or tertiary amine.

[0064] In this descriptive report, a saturated heterocyclic group refers to at least one ring of atoms (including bridging rings, spiro rings, fused rings, and single rings) containing carbon atoms and at least one heteroatom, wherein the heteroatom(s) is / are each independently selected from N, O, and S, and wherein each atom in the ring is linked to its adjacent atoms by single covalent bonds. Therefore, an example of a heterocyclic group is a spiro-heterocyclic group with two rings and a total of one heteroatom, such as 9-azasprio[5.5]undecane. Typically, a saturated heterocyclic group will have at least two carbon atoms separating each of the heteroatoms present in said group to ensure a level Petition 870250080967, dated 09 / 09 / 2025, page 27 / 523 / 482, regarding adequate chemical stability for use in a pharmaceutical context. When reference is made to a saturated (or partially unsaturated) heterocyclic group containing nitrogen, this requires the presence of at least one nitrogen heteroatom, but does not limit the possibility of one or more non-nitrogen heteroatoms (i.e., S, O) being additionally present. In this descriptive report, a partially unsaturated heterocyclic group refers to at least one ring of atoms (including bridging rings, spiro rings, fused rings, and simple rings) containing carbon atoms and at least one heteroatom, wherein the heteroatom(s) is / are each independently selected from N, O, and S, and wherein at least two atoms within the heterocyclic group are connected to each other via a covalent double bond.As those skilled in the art would understand, partially unsaturated does not include completely unsaturated heterocyclic groups—that is, groups containing the maximum possible number of double bonds for the atomic structure in question.

[0065] When reference is made to a cyclic group (e.g., a heterocyclic group) with a specified number of atoms in the ring, this includes the atoms that make up the ring (including atoms involved in bridging a bridging ring and all atoms of a fused or spiro ring), but does not include any hydrogen atoms or other substituent atoms bonded to the atoms in the ring. Therefore, for example, a cyclic group that is 1,4-piperazin-1,4-di-yl has 6 atoms in the ring (4C and 2N).

[0066] In this descriptive report, an alkylene group (e.g., a C1-5-alkylene) is a saturated group consisting only of carbon and hydrogen atoms with two point attachments to adjacent atoms / groups. They may include linear chain(s), branched chain(s), and / or ring(s). Consequently, C1-5-alkylene represents -CH2-, a C2-alkylene may represent -CH2CH2- or -CH(Me)-, C1-5-alkylene includes, for example Petition 870250080967, dated 09 / 09 / 2025, p. 28 / 523 / 482 CH2(cyclobut-1,3-di-yl)-. A linear chain CuI-U2-alkylene corresponds to -(CH2)u-, where u is an integer from u1 to u2.

[0067] In this descriptive report, a hydrocarbyl group means Any group consisting only of C and H atoms. For example, C17hydrocarbyl includes methyl, phenyl, and p-tolyl.

[0068] The term therapy is intended to have its normal meaning of dealing with a disease, in order to alleviate totally or partially one, some, or all of its symptoms, or to correct or compensate for the underlying pathology. The terms therapeutically and therapeutically should be interpreted in a corresponding manner.

[0069] The term treatment is used as a synonym for therapy. From Similarly, the term "treat" can be considered as "apply therapy," where therapy is as defined here.

[0070] Some values ​​for groups of variables are as follows. One, two, or more of these values ​​may be used in any combination with any other definitions, claims, aspects, or embodiments herein. (unless the context does not allow) to provide Additional details / claims of the descriptive report.

[0071] In one modality, X1 is CH.

[0072] In one modality, X1 is N.

[0073] In one modality, RN is H.

[0074] In one modality, RN is Me.

[0075] In one modality, X1 is CH and RN is H.

[0076] In one modality, X1 is CH and RN is Me.

[0077] In one modality, X1 is N and RN is H.

[0078] In one modality, X1 is N and RN is Me.

[0079] In one modality, p is 0.

[0080] In one modality, p is 0 or 1.

[0081] In one modality, p is 1 or 2. Petition 870250080967, dated 09 / 09 / 2025, page 29 / 523 / 482

[0082] In one mode, p is 1.

[0083] In one mode, p is 2.

[0084] to Q1. When p is 1, R1 can be connected in the position for in relation to

[0085] When p is 2, an R1 can be connected in the position for in in relation to Q1, and the other R1 may be in the ortho or meta position in relation to Q1.

[0086] In one embodiment, each R1 is selected from F, Cl, methyl, CF3, methoxy and OCF3.

[0087] methyl. In one embodiment, each R1 is selected from F, Cl and

[0088] methyl. In one embodiment, p is 1 and R1 is selected from F, Cl and

[0089] In one embodiment, p is 1 and R1 is selected from F and Cl.

[0090] In one embodiment, n is 0.

[0091] In one embodiment, n is 1.

[0092] In one embodiment, n is 2.

[0093] In one embodiment, m is 0.

[0094] In one embodiment, m is 1.

[0095] In one embodiment, n is 0 and is 1.

[0096] In one embodiment, n is 1 and is 1.

[0097] In one embodiment, n is 2 and is 0.

[0098] In one embodiment, n is 0, m is 1, Q1 is N and Q2 is CH.

[0099] In one modality, n is 1, m is 1, Q1 is CH and Q2 is CH.

[00100] In one modality, n is 1, m is 1, Q1 is N and Q2 is CH or N.

[00101] In one modality, n is 2, m is 0, Q1 is N and Q2 is CH.

[00102] In one modality, n is 2, m is 0, Q1 is N, Q2 is CH and Q3 is CH.

[00103] In one modality, n is 2, m is 0, Q1 is N, Q2 is CH and Q3 is O.

[00104] In one modality, Q1 is N, Q2 is CH and Q3 is CH. Petition 870250080967, dated 09 / 09 / 2025, page 30 / 523 / 482

[00105] In one modality, Q1 is N, Q2 is CH and Q3 is CH, then they are 1 and 1 or 2 and 0, respectively.

[00106] In one modality, R2aé H and R2bé H.

[00107] In one embodiment, n is 1, m is 0, R2a is H and R2bé is Q^alkyl bonded to a C atom, except in Q1 and Q2, wherein said C atom has a stereochemical configuration (R).

[00108] In one embodiment, n is 1, m is 0, R2a is H and R2bé is Q^alkyl bonded to a C atom, except in Q1 and Q2, wherein said C atom has a stereochemical configuration (S).

[00109] In one embodiment, n is 1, m is 1, R2a is H and R2bé is Q^alkyl bonded to a C atom, except in Q1 and Q2, wherein said C atom has a stereochemical configuration (R).

[00110] In one embodiment, n is 1, m is 1, R2a is H and R2bé is Q^alkyl bonded to a C atom, except in Q1 and Q2, wherein said C atom has a stereochemical configuration (S).

[00111] In one embodiment, Q1 is CH with a stereochemical configuration (R) at said C atom.

[00112] In one embodiment, Q1 is CH with a stereochemical configuration (S) at said C atom.

[00113] In one embodiment, n is 2; m is 0; R2 and R2b are both H; Q1 is CH and Q2 is N.

[00114] In one embodiment, n is 2; m is 0; R2 and R2b are both H; Q2 is N and Q1 is CH with a stereochemical configuration (R) on said C atom.

[00115] In one embodiment, n is 2; m is 0; R2 and R2b are both H; Q2 is N and Q1 is CH with a stereochemical configuration (S) on said C atom.

[00116] In one embodiment, Q2 is CH with a stereochemical configuration (R) on said C atom.

[00117] In one embodiment, Q2e CH with a stereochemical configuration (S) at said C atom. Petition 870250080967, dated 09 / 09 / 2025, p. 31 / 523 / 482

[00118] In one embodiment, n is 2; m is 0; R2 and R2b are both H; Q1 is N and Q2 is CH.

[00119] In one embodiment, n is 2; m is 0; R2 and R2b are both H; Q1 is N and Q2 is CH with a stereochemical configuration (R) on said C atom.

[00120] In one embodiment, n is 2; m is 0; R2 and R2b are both H; Q1 is N and Q2 is CH with a stereochemical configuration (S) on said C atom.

[00121] In one embodiment, R2ae R2b are substituents on the same or different C atoms, except at Q, each independently selected from H and C1-3 alkyl.

[00122] In one embodiment, R2ae R2b are substituents on the same or different C atoms, except for Q, each independently selected from H and Me.

[00123] In one embodiment, R2ae R2b are substituents on the same or different C atoms in a position adjacent to Q and, otherwise, are as defined herein.

[00124] In one embodiment, R2ae R2b are substituents on the same or different C atoms in a position adjacent to Q, each independently selected from H and C1-3 alkyl (e.g., Me).

[00125] In one embodiment, R2ae R2b are substituents on the same C atoms or on different atoms and are both H.

[00126] In one embodiment, R2ae R2b are substituents on the same or different C atoms, except at Q, each independently from among H, F and C1-3 alkyl.

[00127] In one embodiment, R2ae R2b are substituents on the same or different C atoms, except at Q, each independently selected from H and C1-3 alkyl, or R2ae R2b together form an (CH2) r- group, wherein r is 1, 2, or 3.

[00128] In one embodiment, R2a and R2b are substituents on the same or different C atoms, except at Q, where R2a is Me and R2b is H. Petition 870250080967, dated 09 / 09 / 2025, p. 32 / 523 / 482

[00129] In one embodiment, R2ae R2b are substituents on the same C atom, except at Q, where R2ae R2b are both Me.

[00130] In one embodiment, R2ae R2b are substituents on the same C atom in a position adjacent to Q, where R2ae R2b are both Me.

[00131] In one embodiment, Q4 is a simple link.

[00132] In one modality, Q4 is an NR4C(=O) and R4 is H.

[00133] In one embodiment, Q4 is an NR4C(=O) and R4 is methyl.

[00134] In one modality, Q4 is an NR4C(=O), R4 is H and Q2 is CH.

[00135] In one embodiment, Q4 is an NR4C(=O), R4 is methyl and Q2 is CH.

[00136] In one embodiment, Y1, Y2, Y3, Y4 and Y5 are, respectively, selected from (C, C, C, C, C), (N, C, C, C, C), (C, N, C, C, C), (N, C, C, N, C), (N, N, C, C, C), (N, C, N, C, C), (C, N, C, N, C) and (C, N, N, C, C).

[00137] In one embodiment, Y1, Y2, Y3, Y4 and Y5 are selected, respectively, from (C, C, C, C, C), (N, C, C, C, C) and (N, N, C, C, C).

[00138] In one embodiment, 0 or 1 among Y1, Y2, Y3, Y4 and Y5 is N and, otherwise, they are C.

[00139] In one embodiment, 1 or 2 of Y1, Y2, Y3, Y4 and Y5 are N and, otherwise, are C.

[00140] In one embodiment, 1 out of Y1, Y2, Y3, Y4 and Y5 is N and, otherwise, they are C.

[00141] In one embodiment, Y1 is N; and Y2, Y3, Y4 and Y5 are all C.

[00142] In one embodiment, Y2 is N; and Y2, Y3, Y4 and Y5 are all C.

[00143] In one embodiment, 2 out of Y2, Y3, Y4 and Y5 are N and, otherwise, are C.

[00144] In one embodiment, Y1 and Y3 are N; and Y2, Y4 and Y5 are C.

[00145] In one embodiment, Y1 and Y2 are N; and Y3, Y4 and Y5 are C.

[00146] In one embodiment, Y1 and Y4 are N; and Y2, Y3 and Y5 are C.

[00147] In one embodiment, Y2 and Y3 are N; and Y1, Y4 and Y5 are C. Petition 870250080967, dated 09 / 09 / 2025, page 33 / 523 / 482

[00148] In one modality, Y2 and Y4 are N; and Y1, Y3, and Y5 are C.

[00149] In one modality, Y1, Y2, Y3, Y4, and Y5 are all C.

[00150] In one modality, q is 0 or 1.

[00151] In one modality, q is 0.

[00152] In one modality, q is 1.

[00153] In one modality, q is 2.

[00154] In one modality, q is 0, 1, or 2, and R3 (when present) is a a substituent on any C atom in Y1, Y2, Y3, Y4 and Y5 selected from F, CN and C1-3 alkyl.

[00155] In one modality, q is 0, 1, or 2 and R3 (when present) is a Substitution on any C atom in Y1, Y2, Y3, Y4 and Y5 selected from F, CN and methyl.

[00156] In one modality, q is 0 or 1 and R3 (when present) is a The substituent on any C atom in Y1, Y2, Y3, Y4, and Y5 is F.

[00157] In one embodiment, R3 (when present) is C1-3 alkyl.

[00158] In one embodiment, R3 (when present) is Me.

[00159] In one embodiment, R3 (when present) is F.

[00160] In one embodiment, R3 (when present) is CN.

[00161] In one embodiment, q is 1 and R3 is attached to C in Y1.

[00162] In one embodiment, q is 1 and R3 is attached to C in Y1, and R3 is selected from F, CN and Me.

[00163] In a modality q is 1 and R3 is connected to C in Y2, and R3 is selected between CN and Me.

[00164] In one modality, q is 2 and both R3 groups are F or a Group F is the first and the other group is Me.

[00165] Y1 and Y3. In one embodiment, q is 2 and the R3 groups are linked to C in

[00166] In one embodiment, q is 2 and each R3 group is F, which are connected to C in Y1 and Y3. Petition 870250080967, dated 09 / 09 / 2025, p. 34 / 523 / 482

[00167] In one embodiment, q is 2, an R3 group is F, which is linked to C in Y1, and an R3 group is Me, which is linked to C in Y3.

[00168] In one embodiment, the Ligand is linked in Y5.

[00169] In one embodiment, the Ligand is linked to Y4.

[00170] In one embodiment, the group of formula (Ia) is of formula (Ia1): (Ia-1) where R1 and Q1 are as defined above. Q1 is CH or N.

[00171] In one embodiment, the group of formula (Ia) is of formula (Ia2): i (Ia-2) where R1, Q1, Q2 and Q3 are as defined above. Q1 is CH or N; Q2 is CH or N; when Q2 is N, Q3 is CH; when Q2 is CH, Q3 is CH or O.

[00172] In one embodiment, the group of formula (Ia) is of formula (Ia3): Petition 870250080967, dated 09 / 09 / 2025, page 35 / 523 / 482 (Ia-3) where R1 is as defined above.

[00173] In one embodiment, the Ligand is a saturated or partially or completely unsaturated structure comprising C and H atoms and at least one heteroatom, said structure having terminal bonding points 'a' and 'b' and a minimum length of 5 to 26 atoms between 'a' and 'b'; said structure may include one or more linear and / or branched chains and / or rings and is optionally replaced at any available C atom(s) by one or more F.

[00174] In one embodiment, the ligand structure is a saturated or partially unsaturated structure.

[00175] In one embodiment, the Ligand structure is a saturated structure.

[00176] In one embodiment, the Ligand structure comprises C and H atoms and at least two heteroatoms.

[00177] In one embodiment, the Ligand structure comprises C and H atoms and at least two heteroatoms selected from O and N.

[00178] In one embodiment, the Ligand structure comprises C and H atoms and at least one nitrogen heteroatom.

[00179] In one embodiment, the Ligand structure comprises C and H atoms and at least two heteroatoms, including at least one nitrogen heteroatom. Petition 870250080967, dated 09 / 09 / 2025, p. 36 / 523 / 482

[00180] In one embodiment, the Ligand structure comprises C and H atoms and at least one nitrogen heteroatom in the form of a secondary or tertiary amine.

[00181] In one embodiment, the Ligand structure comprises C and H atoms and at least one nitrogen heteroatom in the form of a tertiary amine.

[00182] In one embodiment, the Ligand structure comprises C and H atoms and at least two heteroatoms, including at least one nitrogen heteroatom in the form of a secondary or tertiary amine.

[00183] In one embodiment, the Ligand structure comprises C and H atoms and at least two heteroatoms, including at least one nitrogen heteroatom in the form of a tertiary amine.

[00184] In one embodiment, the Ligand has a minimum length of 5 to 20 atoms between 'a' and 'b'.

[00185] In one embodiment, the Ligand has a minimum length of 5 to 15 atoms between 'a' and 'b'.

[00186] In one embodiment, the Ligand has a minimum length of 5 to 14 atoms between 'a' and 'b'.

[00187] In one embodiment, the total number of heteroatoms in the ligand structure is from 6 to 26.

[00188] In one embodiment, the total number of heteroatoms in the ligand structure is from 7 to 24.

[00189] In one embodiment, the total number of heteroatoms in the ligand structure is from 7 to 22.

[00190] In one embodiment, the total number of heteroatoms in the ligand structure is 7 to 20.

[00191] In one embodiment, the total number of heteroatoms in the ligand structure is from 7 to 18. Petition 870250080967, dated 09 / 09 / 2025, p. 37 / 523 / 482

[00192] In one embodiment, when W is -Z-RA, the ligand is bonded to any available C atom in XB or XC of Z.

[00193] In one embodiment, the Ligand structure may include one or more linear chains and / or rings and is optionally replaced at any available C atom(s) by one or more F atoms.

[00194] In one embodiment, the Ligand structure consists of one or more linear chains and / or rings that are optionally replaced at any available C atom(s) by one or more F atoms.

[00195] In one embodiment, the structure of the Ligand may include (or consist of) one or more linear and / or branched chains and / or rings (the total number of branches being from 0 to 5) that are optionally replaced at any available C atom(s) by one or more F atoms.

[00196] In one embodiment, the structure of the Ligand may include (or consist of) one or more linear and / or branched chains and / or rings (the total number of branches being from 0 to 3) that are optionally replaced at any available C atom(s) by one or more F atoms.

[00197] In one embodiment, the structure of the Ligand may include (or consist of) one or more linear and / or branched chains and / or rings (where the total number of branches is 0 or 1) that are optionally replaced at any available C atom(s) by one or more F atoms.

[00198] In one modality, the total number of branches is 0.

[00199] In one modality, the total number of branches is 1.

[00200] In one modality, the total number of branches is 2.

[00201] In one modality, the total number of branches is 3.

[00202] In one embodiment, any / each branch in the structure of a Ligand has from 1 to 5 C atoms and / or heteroatoms.

[00203] In one embodiment, any / each branch in the structure of a Ligand has 1 or 2 C atoms and / or heteroatoms. Petition 870250080967, dated 09 / 09 / 2025, p. 38 / 523 / 482

[00204] In one embodiment, any / each branch in the structure of a Ligand has 1 C atom and / or heteroatom.

[00205] In one embodiment, any / each branch in the structure of a Ligand has 1 C atom.

[00206] In one embodiment, the total number of C atoms and / or heteroatoms in the branch(es) (when present) of the Ligand structure is from 1 to 5.

[00207] In one embodiment, the total number of C atoms and / or heteroatoms in the branch(es) (when present) of the Ligand structure is from 1 to 3.

[00208] In one embodiment, the total number of C atoms and / or heteroatoms in the branch(es) (when present) of the Ligand structure is 1.

[00209] In one embodiment, the Ligand structure is unbranched or has a branch that is Me.

[00210] In one embodiment, the Ligand structure is unbranched.

[00211] In one embodiment, the Ligand structure is optionally replaced at any available C atom(s) by 1 or 2 F (for example, by 2 F, wherein said 2 F are substituted at the same carbon atom).

[00212] In one embodiment, the structure of the Ligand is not replaced by any F.

[00213] In one embodiment, the Ligand is a saturated or partially unsaturated structure comprising C and H atoms and at least one heteroatom, said structure having terminal bonding points 'a' and 'b' and: a minimum length of 5 to 14 atoms between 'a' and 'b'; where the total number of C atoms and heteroatoms in the Ligand structure is 7 to 18; Petition 870250080967, dated 09 / 09 / 2025, p. 39 / 523 / 482, in which said structure comprises one or more linear chains and / or rings that are optionally substituted at any available C atom(s) by 1 or 2 F (for example, by 2 F).

[00214] In one embodiment, the structure of the Ligand includes at least one saturated or partially unsaturated heterocyclic group containing nitrogen (for example, having from 4 to 12 atoms in the ring) or an A1CH2-CH2-A2 unit, wherein A1 and A2 are each independently selected from N and O.

[00215] In one embodiment, the structure of the Ligand includes at least one saturated heterocyclic group containing nitrogen (for example, having from 4 to 12 atoms in the ring) or an A1-CH2-CH2-A2 unit, wherein A1 and A2 are each independently selected from N and O.

[00216] In one embodiment, the structure of the Ligand includes an A1-CH2-CH2-A2 unit, wherein A1 and A2 are each independently selected from N and O.

[00217] In one embodiment, the structure of the Ligand includes at least one saturated or partially unsaturated heterocyclic group containing nitrogen (for example, having from 4 to 12 atoms in the ring) or an A1CH2-CH2-A2 unit, wherein one of A1 and A2 is N and the other of A1 and A2 is selected from N or O.

[00218] In one embodiment, the structure of the Ligand includes at least one heterocyclic group containing nitrogen (for example, having from 4 to 12 atoms in the ring) or an A1-CH2-CH2-A2 unit, wherein one of A1 and A2 is N and the other of A1 and A2 is selected from N or O.

[00219] In one embodiment, the structure of the Ligand includes an A1-CH2-CH2-A2 unit, wherein one of A1 and A2 is N and the other of A1 and A2 is selected from N or O.

[00220] In one embodiment, the structure of the Ligand includes at least one saturated or partially unsaturated heterocyclic group containing Petition 870250080967, dated 09 / 09 / 2025, page 40 / 523 / 482 nitrogen (for example, having 4 to 12 atoms in the ring) or an A1CH2-CH2-A2 unit, wherein one of A1 and A2 is N in the form of a secondary or tertiary amine, and the other of A1 and A2 is selected from N or O.

[00221] In one embodiment, the structure of the Ligand includes an A1-CH2-CH2-A2 unit, wherein one of A1 and A2 is N in the form of a secondary or tertiary amine, and the other of A1 and A2 is selected from N or O.

[00222] In one embodiment, the structure of the Ligand includes at least one saturated or partially unsaturated heterocyclic group.

[00223] In one embodiment, the structure of the Ligand includes at least one saturated heterocyclic group.

[00224] In one embodiment, the structure of the Ligand includes at least one saturated or partially unsaturated heterocyclic group containing nitrogen.

[00225] In one embodiment, the Ligand structure includes at least one saturated heterocyclic group containing nitrogen.

[00226] In one embodiment, the Ligand structure includes at least one saturated or partially unsaturated heterocyclic group containing nitrogen having from 4 to 12 atoms in the ring.

[00227] In one embodiment, the Ligand structure includes at least one saturated heterocyclic group containing nitrogen having from 4 to 12 atoms in the ring.

[00228] In one embodiment, the structure of the Binder includes: (1) an A1-CH2-CH2-A2 unit, wherein A1 and A2 are each independently selected from N and O; and / or (2) at least one saturated or partially unsaturated heterocyclic group containing nitrogen selected from piperazine, azetidine, piperidine, 1,4-diazepane, 12-oxa-3,9-diazaspiro[5.6]dodecane, pyrrolidine, 3,9-diazaspiro-[5.5]undecane, 2,5-diazabicyclo[2.2.1]heptane, Petition 870250080967, dated 09 / 09 / 2025, page 41 / 523 / 482 1,2,3,3a,4,5,6,6a-octahydropyrrolo[3,4-c]pyrrole, 1,2,3,6-tetrahydropyridine, morpholine, 2-azaspiro[3.5]nonane and 9-azaspiro[5.5]undecane.

[00229] In one embodiment, the structure of the Binder includes: (1) an A1-CH2-CH2-A2 unit, wherein one of A1 and A2 is N in the form of a secondary or tertiary amine, and the other of A1 and A2 is selected from N or O; and / or (2) at least one saturated or partially unsaturated heterocyclic group containing nitrogen selected from piperazine, azetidine, piperidine, 1,4-diazepane, 12-oxa-3,9-diazaspiro[5.6]dodecane, pyrrolidine, 3,9-diazaspiro-[5.5]undecane, 2,5-diazabicyclo[2.2.1]heptane, 1,2,3,3a,4,5,6,6a-octahydropyrrolo[3,4-c]pyrrole, 1,2,3,6-tetrahydropyridine, morpholine, 2-azaspiro[3.5]nonane and 9-azaspiro[5.5]undecane.

[00230] In one embodiment, the structure of the Ligand includes at least one saturated or partially unsaturated heterocyclic group containing nitrogen selected from piperazine, azetidine, piperidine, 1,4-diazepane, 12-oxa-3,9-diazaspiro[5.6]dodecane, pyrrolidine, 3,9-diazaspiro[5.5]undecane, 2,5-diazabicyclo[2.2.1]heptane, 1,2,3,3a, 4,5,6,6a-octahydropyrrolo[3,4c]pyrrole, 1,2,3,6-tetrahydropyridine, morpholine, 2-azaspiro[3.5]nonane and 9-azaspiro[5.5]undecane.

[00231] In one embodiment, the structure of the Ligand includes an O-CH2-CH2-N unit.

[00232] In one embodiment, the structure of the Ligand includes: an O-CH2CH2-O-CH2CH2-N unit.

[00233] In one embodiment, the Ligand structure includes a piperazine group.

[00234] In one embodiment, the Ligand structure includes an azetidine group.

[00235] In one embodiment, the structure of the Ligand includes a piperidine group. Petition 870250080967, dated 09 / 09 / 2025, page 42 / 523 / 482

[00236] In one embodiment, the structure of the Ligand includes a 1,4-diazepane group.

[00237] In one embodiment, the structure of the Ligand includes a 12-oxa-3,9-diazaspiro[5.6]dodecane group.

[00238] In one embodiment, the structure of the Ligand includes a pyrrolidine group.

[00239] In one embodiment, the structure of the Linker includes a group 3,9-diazaspir[5.5]undecane.

[00240] In one embodiment, the structure of the Linker includes a group 2,5-diazabicyclo[2.2.1]heptane.

[00241] In one embodiment, the structure of the Ligand includes a 1,2,3,3a,4,5,6,6a-octahydropyrrolo[3,4-c]pyrrole group.

[00242] In one embodiment, the structure of the Ligand includes a 1,2,3,6-tetrahydropyridine group.

[00243] In one embodiment, the Ligand structure includes a morpholine group.

[00244] In one embodiment, the Ligand structure includes a 2azaspiro[3.5]nonane group.

[00245] In one embodiment, the structure of the Ligand includes an azaspiro[5.5]undecane group.

[00246] In one embodiment, the structure of the Ligand includes at least two saturated or partially unsaturated heterocyclic groups containing nitrogen.

[00247] In one embodiment, the structure of the Ligand includes at least two saturated heterocyclic groups containing nitrogen.

[00248] In one embodiment, the Ligand structure includes a C, N, or O atom at the 'a' bonding point.

[00249] In one embodiment, the Ligand structure includes an N or O atom at the 'a' bonding point. Petition 870250080967, dated 09 / 09 / 2025, p. 43 / 523 / 482

[00250] In one embodiment, the ligand structure includes an N or O atom at the 'b' bonding point.

[00251] In one embodiment, that of C at the connection point 'a'.

[00252] In one embodiment, that of N at the connection point 'a'.

[00253] In one embodiment, that of C or of N at the connection point 'b'.

[00254] In one embodiment, that of N at the connection point 'b'.

[00255] In one embodiment, that of C at the connection point 'b'.

[00256] In one embodiment, that of O at the connection point 'a'.

[00257] In one embodiment, that of O at the connection point 'b'.

[00258] In one embodiment, the Ligand structure includes an atom of N or O at both the 'a' and 'b' bonding points.

[00259] In one embodiment, the Ligand structure includes a C, N, or O atom at the 'a' bonding point and a C or N atom at the 'b' bonding point.

[00260] In one embodiment, the structure of the Binder includes: (1) an A1-CH2-CH2-A2 unit, wherein one of A1 and A2 is N in the form of a secondary or tertiary amine, and the other of A1 and A2 is selected from N or O; and / or (2) at least one saturated or partially saturated heterocyclic group containing nitrogen selected from piperazin-1,4-di-yl, azetidin-1,3-di-yl, piperidin-1,4-di-yl, 1,4-diazepan-1,4-di-yl, 12-oxa3,9-diazaspiro[5.6]dodecan-3,9-di-yl, pirrolidin-1,3-di-yl, 3,9 Petition 870250080967, dated 09 / 09 / 2025, page 44 / 523 / 482 diazaspiro[5.5]undecan-3,9-di-ila, 2,5-diazabiciclo[2.2.1]heptan-2,5-di-ila, 1,3,3a,4,6,6a-hexa-hydropirrolo[3,4-c]pyrrol-2,5-di-ila, 3,6-dihydro-2 Hpiridin-1,4-di-ila, morfolin-2,3-di-ila, 2-azaspiro[3.5]nonan-2,7-di-ila and 9azaspiro[5.5]undecan-3,9-di-ila.

[00261] In one embodiment, the structure of the Ligand includes at least one saturated or partially saturated heterocyclic group containing nitrogen selected from piperazin-1,4-di-yl, azetidin-1,3-di-yl, piperidin-1,4-di-yl, 1,4-diazepan-1,4-di-yl, 12-oxa-3,9-diazaspiro[5.6]dodecan-3,9-di-yl, pirrolidin-1,3-di-yl, 3,9-diazaspiro[5.5]undecan-3,9-di-yl, 2,5-diazabicyclo[2.2.1]heptan-2,5-di-yl, 1,3,3a,4,6,6a-hexahydropyrrolo[3,4c]pyrrol-2,5-di-yl, 3,6-dihydro-2H-pyridin-1,4-di-yl, morpholin-2,3-di-yl, 2azaspiro[3.5]nonan-2,7-di-yl and 9-azaspiro[5.5]undecan-3,9-di-yl.

[00262] In one embodiment, the structure of the Ligand includes a piperazin-1,4-di-yl group.

[00263] In one embodiment, the structure of the Ligand includes an azetidin-1,3-di-yl group.

[00264] In one embodiment, the structure of the Ligand includes a piperidin-1,4-di-yl group.

[00265] In one embodiment, the structure of the Ligand includes a 1,4-diazepan-1,4-di-yl group.

[00266] In one embodiment, the structure of the Ligand includes a 12-oxa-3,9-diazaspiro[5.6]dodecan-3,9-di-ila group.

[00267] In one embodiment, the structure of the Ligand includes a pyrrolidin-1,3-di-yl group.

[00268] In one embodiment, the structure of the Ligand includes a 3,9-diazaspiro[5.5]undecan-3,9-di-ila group.

[00269] In one embodiment, the structure of the Ligand includes a 2,5-diazabicyclo[2.2.1]heptan-2,5-di-yl group. Petition 870250080967, dated 09 / 09 / 2025, page 45 / 523 / 482

[00270] In one embodiment, the structure of the Ligand includes a 1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-2,5-di-yl group.

[00271] In one embodiment, the structure of the Ligand includes a 3,6-dihydro-2H-pyridin-1,4-di-yl group.

[00272] In one embodiment, the structure of the Ligand includes a morpholin-2,3-di-yl group.

[00273] In one embodiment, the structure of the Ligand includes a 2azaspiro[3.5]nonan-2,7-di-yl group.

[00274] In one embodiment, the structure of the Ligand includes an 9azaspiro[5.5]undecan-3,9-di-yl group.

[00275] In one embodiment, the Binder has the formula: 'a' -Qa-Qb-Qc- 'b' where: 'a' and 'b' represent the final connection points; Qa is -G-Qh- or -G-(C1-5alkylene)-; Qbé is a direct linkage, -QB1-QB2-QB3- or Q^alkylene optionally substituted by one or more F (e.g. 1 or 2 F, e.g. 2 F); wherein: Qb1e QB3 each independently represent a direct or C1-2 alkylene bond; QB2 is Qh, -O-CH2CH2-O-, -O- or -N(RJ)-, where RJ is H or C1-3 alkyl; Qcé -Qh-G- or -(C1-5alkylene)-G-; each G is independently a direct linkage, -CH2-, -O-, C(=O)- or -N(RG)-, where each RG is independently H or C1-3 alkyl; Each Qhé is, independently, a saturated or partially unsaturated heterocyclic group containing nitrogen with 4 to 12 members; where the values ​​of Qa, Qb and Qc are selected so that the ligand does not contain any NN or NO bonds. Petition 870250080967, dated 09 / 09 / 2025, p. 46 / 523 / 482

[00276] In one embodiment, the Binder has the formula: 'a' -Qa-Qb-Qc- 'b' where: 'a' and 'b' represent the final connection points; Qa is -G-Qh- or -G-(C1-5alkylene)-; Qbé is a direct linkage, -QB1-QB2-QB3- or Q^alkylene optionally substituted by one or more F (e.g., 1 or 2); wherein: Qb1e QB3 each independently represent a direct or C1-2 alkylene bond; QB2 is Qh, -O-CH2CH2-O- or -N(RJ)-, where RJ is C1I-3 alkyl; Qcé -Qh-G- or -(Ci—5alkylene)-G-; each G is independently a direct linkage, -CH2-, C(=O)-, -O- or -N(RG)-, where each RG is independently H or C13 alkyl; Each Qhé is, independently, a saturated or partially unsaturated heterocyclic group containing nitrogen with 4 to 12 members; where the values ​​of Qa, Qb and Qc are selected so that the ligand does not contain any NN or NO bonds.

[00277] In one embodiment, the Binder has the formula: 'a' -Qa-Qb-Qc- 'b' where: 'a' and 'b' represent the final connection points; Qaé -Ga-Qha- or -GA-(Ci-5alkylene)-; where Gaé is a direct bond, -CH2-, -C(=O)-, -O-, -NH- or -N(Me)-; Qha is a saturated heterocyclic group containing nitrogen with 4 to 11 members; Qbé is a direct linkage, -Qb1-QB2-QB3- or Q^alkylene optionally substituted by one or more F (e.g., 1 or 2); wherein: Petition 870250080967, dated 09 / 09 / 2025, p. 47 / 523 / 482 QB1eqB3 each independently represent a direct or C1-2 alkylene bond; QB2 is piperazine-1,4-di-yl, -O-CH2CH2-O- or -N(RJ)-, where RJ is C1I-3 alkyl; QCé -QHC-GC- or -(C1-2-alkylene)-GC-; where GC is a direct bond, -O- or -NH-; QHC is a saturated or partially unsaturated heterocyclic group containing nitrogen with 6 to 12 members; where the QA, QB and QC values ​​are selected so that the ligand does not contain any NN or NO bonds.

[00278] In one embodiment, QA is -GA-QHA- or -GA-(C1-5-alkylene)-, wherein: GA is selected from a direct bond, -CH2-, -C(=O)-, -O or -N(RG)-; each Rgé, independently, H or C1-3 alkyl; and QHA is a saturated heterocyclic group containing nitrogen from 4 to 2 members.

[00279] In one embodiment, QA is -GA-QHA- or -GA-(C1-5-alkylene)-, wherein: GA is selected from a direct bond, -CH2-, -C(=O)-, O- or -N(RG)-; each Rgé, independently, H or C1-3 alkyl; and QHA is selected from azetidin-i,3-di-ila, morfolin-2,3-diila, pirrolidin-i,3-di-ila, piperidin-i,4-di-ila, piperazin-i,4-di-ila, 3,9diazaspiro[5.5]undecan-3,9-di-ila, 2-azaspiro[3.5]nonan-2,7-di-ila and 9azaspiro[5.5]undecan-3,9-di-ila.

[00280] In one embodiment, QA is -GA-QHA- or -GA-(C1-5-alkylene)-, wherein: Petition 870250080967, dated 09 / 09 / 2025, page 48 / 523 / 482 GA is selected from a direct bond, -CH2-, -C(=O)-, O- or -NH- or -N(Me)-; Qhaé is selected from azetidin-1,3-di-yl, pirrolidin-1,3-di-yl, piperidin-1,4-di-yl, piperazin-1,4-di-yl, 3,9-diazaspiro[5.5]undecan-3,9-di-yl and 9-azaspiro[5.5]undecan-3,9-di-yl; and the C1-5-alkylene in said -GA-(C1-5-alkylene)- is selected from -(CH2)f-, wherein f is an integer from 1 to 5, cyclobut-1,3-di-yl and CH2(cyclobut-1,3-di-yl)-.

[00281] In one embodiment, Qaé is selected from azetidine-1,3-diyl, pyrrolidine-1,3-di-yl, piperidine-1,4-di-yl, -O(piperidine-1,4-di-yl)-, -C(O)piperidine-1,4-di-yl, -CH2(piperidine-1,4-di-yl), piperazine-1,4-di-yla, 3,9diazaspiro[5.5]undecane-3,9-di-yla, morpholin-2,3-di-yla, 2-azaspiro[3.5]nonan2,7-di-yla, -O(9-azaspiro[5.5]undecan-3,9-di-yla), -O(1,3,3-di-lo) OCH2(cyclobut-1,3-di-yla)-, -(CH2)f-, -O-(CH2)f-, -NH-(CH2)f- and -N(Me)(CH2)f-, in which f is an integer from 1 to 5.

[00282] In one embodiment, Qaé azetidine-1,3-di-ila.

[00283] In one embodiment, Qaé pyrrolidin-1,3-di-yl.

[00284] In one embodiment, Qaé piperidine-1,4-di-yl.

[00285] In one embodiment, Qaé -C(O)-piperidine-1,4-di-ila.

[00286] In one embodiment, Qaé -O(piperidine-1,4-di-ila)-.

[00287] In one embodiment, Qaé -CH2(piperidine- 1,4-di-ila)-.

[00288] In one embodiment, Qaé piperazine-1,4-di-ila.

[00289] In one embodiment, Qaé -CH2(piperazin-1,4-di-ila)-.

[00290] In one embodiment, Qa is morpholin-2,3-di-yl.

[00291] In one embodiment, Qa is 2-azaspiro[3,5]nonan-2,7-di-yl.

[00292] In one embodiment, Qaé 3,9-diazaspiro[5.5]undecan-3,9-diila.

[00293] In one form, Qaé -O(9-azaspiro[5,5]undecan-3,9-diila)-. Petition 870250080967, dated 09 / 09 / 2025, page 49 / 523 / 482

[00294] In one embodiment, QA is -G-(C1-5-alkylene)-.

[00295] In one embodiment, QA is selected from -O(cyclobut-1,3-di-yl)-, -OCH2(cyclobut-1,3-di-yl)-, -(CH2)f-, -O(CH2)f-, -NH-(CH2)f- and N(Me)-(CH2)f-, where f is an integer from 1 to 5.

[00296] In one form, QAé -O(cyclobut-1,3-di-ila)-.

[00297] In one embodiment, QAé -OCH2(cyclobut-1,3-di-yl)-.

[00298] In one embodiment, QA is -(CH2)f-, where f is an integer from 1 to 4 (for example, f is 4)

[00299] In one embodiment, QA is -O-(CH2)f-, where f is an integer from 1 to 5 (for example, f is 4).

[00300] In one embodiment, QA is -NH-(CH2)f-, where f is an integer from 1 to 5.

[00301] In one embodiment, QAé -N(Me)-(CH2)f-, where f is an integer from 1 to 4.

[00302] In one embodiment, QB is a direct linkage, -QB1-QB2-QB3 or a linear chain C1-3 alkylene optionally substituted by one or more F (e.g. 1 or 2 F, e.g. by 2 F).

[00303] In one modality, QB is a direct connection.

[00304] In one modality, QBé -QB1-QB2-QB3-.

[00305] In one embodiment, QBé C1-3alkylene optionally replaced by one or more F.

[00306] In one embodiment, QBé C1-3alkylene optionally substituted by one or two F (e.g., by 2 F).

[00307] In one embodiment, QB is a linear chain C1-3 alkylene optionally substituted by 1 or 2 F (e.g., by 2 F).

[00308] In one embodiment, QBé C1-3alkylene.

[00309] In one embodiment, QB is a linear chain C1-3 alkylene.

[00310] In one form, QBé -CF2-CH2-CH2- or -(CH2)w-, where w is 1 to 3. Petition 870250080967, dated 09 / 09 / 2025, page 50 / 523 / 482

[00311] In one modality, QB1 and QB3 each represent, Regardless, a direct link, -CH2- or -CH2CH2-.

[00312] In one modality, QB1 is a direct link or -CH2-.

[00313] In one modality, QB1 is a direct link.

[00314] In one modality, QB1 is -CH2-.

[00315] CH2CH2-. In one modality, QB3 is a direct link, -CH2- or -

[00316] In one modality, QB3 is a direct link.

[00317] In one modality, QB3 is -CH2-.

[00318] In one modality, QB3 is -CH2CH2-.

[00319] In one modality, QB2 is QH, -O-CH2CH2-O- or -N(RJ)-, in RJ is C1-3 alkyl.

[00320] In one embodiment, QB2 is QH, -O-CH2CH2-O- or -N(Me)-.

[00321] In one embodiment, QB2 is piperazin-1,4-di-ila, azetidin-1,3- di-yl, -O-CH2CH2-O- or -N(Me)-.

[00322] In one embodiment, QB2 is piperazin-1,4-di-ila, -O-CH2CH2- O- or -N(Me)-.

[00323] In one embodiment, QB2 is QH.

[00324] In one embodiment, QB2 is piperazin-1,4-di-yl.

[00325] In one embodiment, QB2 is azetidin-1,3-di-yl.

[00326] In one embodiment, QB2 is -O-CH2CH2-O-.

[00327] In one embodiment, QB2 is -N(RJ)-, wherein RJ is C1-3 alkyl.

[00328] In one embodiment, QB2 is -N(Me)-.

[00329] In one embodiment, QC is -QH-G- or -(C1-4 alkylene)-G-.

[00330] In one embodiment, QC is -QH-G- or -(C1-3 alkylene)-G-.

[00331] In one embodiment, QC is -QH-G- or -(C1-2-alkylene)-G-.

[00332] In one embodiment, QC is -QHC-GC- or -(C1-5-alkylene)-GC-, wherein: GC is selected from a direct linkage, -O- or -NH-; and Petition 870250080967, dated 09 / 09 / 2025, page 51 / 523 / 482 Qh is a saturated or partially unsaturated heterocyclic group containing nitrogen with 6 to 12 members.

[00333] In one embodiment, Qcé-Qhc-Gc- or -(C1-2-alkylene)-GC-, wherein: G is selected from a direct bond, -O- or -NH-; and Qh is a saturated or partially unsaturated heterocyclic group containing nitrogen with 6 to 12 members.

[00334] In one embodiment, Qcé-Qhc-Gc- or -(C1-2-alkylene)-GC-, wherein: G is selected from a direct linkage, -O- or -NH-; and Qh is selected from piperazin-1,4-di-yl, piperidin-1,4-di-yl, 2,5-diazabicyclo[2.2.1]heptan-2,5-di-yl, 1,4-diazepan-1,4-di-yl, 3,9-diazaspiro[5.5]undecan-3,9-di-yl, 12-oxa-3,9-diazaspiro[5.6]-dodecan-3,9-di-yl, 1,3,3a,4,6,6a-hexa-hydropyrrolo[3,4-c]pyrrol-2,5-di-yl and 3,6-dihydro-2Hpyridin-1,4-di-yl.

[00335] In one embodiment, Q is selected from piperazin-1,4-diyl, piperidin-1,4-diyl, -(piperidin-1,4-diyl)O-, 2,5-diazabicyclo[2.2.1]heptan-2,5-diyl, 1,4-diazepan-1,4-diyl, 3,9-diazaspiro[5.5]undecan-3,9-diyl, 12oxa-3,9-diazaspiro[5.6]-dodecan-3,9-diyl, 1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2,5-diyl, 3,6-dihydro-2H-pyridin-1,4-diyl and CH2CH2-NH- and -(CH2)gO-, wherein g is an integer of 1 to 4.

[00336] In one embodiment, Q is piperazin-1,4-di-yl.

[00337] In one embodiment, Qcé piperidine-1,4-di-yl.

[00338] In one embodiment, Qcé-(piperidine-1,4-di-yl)O-.

[00339] In one embodiment, Qcé 2,5-diazabiciclo[2.2.1]heptan-2,5di-ila.

[00340] In one embodiment, Qcé 1,4-diazepan-1,4-di-ila.

[00341] In one embodiment, Qcé 3,9-diazaspiro[5.5]undecan-3,9-diila. Petition 870250080967, dated 09 / 09 / 2025, page 52 / 523 / 482

[00342] In one embodiment, QCé 12-oxa-3,9-diazaspiro[5.6]dodecan3,9-di-ila.

[00343] In one embodiment, QCé 1,3,3a,4,6,6a-hexa-hydropyrrolo[3,4c]pyrrol-2,5-di-yl.

[00344] In one embodiment, QCé 3,6-dihydro-2H-pyridin-1,4-diyl.

[00345] In one embodiment, QCé -(C1-5alkylene)-G- [for example, (CH2)gO-, where g is an integer from 1 to 5].

[00346] In one embodiment, QCé -(C1-4alkylene)-G- [for example, (CH2)gO-, where g is an integer from 1 to 4].

[00347] In one embodiment, QCé -(C1-3alkylene)-G- [for example, (CH2)gO-, where g is 1, 2 or 3].

[00348] In one embodiment, QCé -(C1-2alkylene)-G- [for example, (CH2)gO-, where g is 1 or 2].

[00349] In one embodiment, QCé -(CH2)g-GC-, where g is an integer from 1 to 5 and GCé -O- or -NH-.

[00350] In one embodiment, QCé -(CH2)g GC-, where g is 1 or 2 and GCé -O- or -NH-.

[00351] In one embodiment, QCé -CH2CH2NH-.

[00352] In one embodiment, QCé -CH2-.

[00353] In one embodiment, each QH is independently selected from piperazin-1,4-di-yl, azetidin-1,3-di-yl, piperidin-1,4-di-yl, 1,4-diazepan-1,4-di-yl, 12-oxa-3,9-diazaspiro[5.6]dodecan-3,9-di-yl, pyrrolidine-1,3-di-yl, 3,9-diazaspiro[5.5]undecan-3,9-di-yl, 2,5diazabicyclo[2.2.1]heptan-2,5-di-yl, 1,3,3a,4,6,6a-hexahydropyrrolo[3,4c]pyrrol-2,5-di-yl, 3,6-dihydro-2H-pyridin-1,4-di-yl and 9azaspiro[5.5]undecan-3,9-di-yl.

[00354] In one embodiment, each QHé is independently selected from piperazin-1,4-di-yl, azetidin-1,3-di-yl, piperidin-1,4-di-yl, 1,4-diazepan-1,4-di-yl, 12-oxa-3,9-diazaspir[5.6]dodecan-3,9-di-yl, Petition 870250080967, dated 09 / 09 / 2025, page 53 / 523 / 482 pyrrolidine-1,3-di-yl, 3,9-diazaspiro[5.5]undecan-3,9-di-yl, morpholin-2,3-diyl, 2-azaspiro[3.5]nonan-2,7-di-yl, 2,5-diazabicyclo[2.2.1]heptan-2,5-di-yl, 1,3,3a,4,6,6a-hexa-hydropyrrolo[3,4-c]pyrrol-2,5-di-yl and 9azaspiro[5.5]undecan-3,9-di-yl.

[00355] In one embodiment, QH is piperazin-1,4-di-yl.

[00356] In one embodiment, QH is azetidin-1,3-di-yl.

[00357] In one embodiment, QH is piperidin-1,4-di-yl.

[00358] In one embodiment, QH is 1,4-diazepan-1,4-di-yl.

[00359] 3,9-di-yl. In one embodiment, QH is 12-oxa-3,9-diazaspiro[5.6]dodecan-

[00360] In one embodiment, QH is pirrolidin-1,3-di-yl.

[00361] yl. In one embodiment, QH is 3,9-diazaspiro[5.5]undecan-3,9-di-

[00362] di-yl. In one embodiment, QH is 2,5-diazabicyclo[2.2.1]heptan-2,5-

[00363] In one embodiment, QH is 1,3,3a,4,6,6a-hexa-hydropyrrolo[3,4- c ]pirrol-2,5-di-ila.

[00364] In one embodiment, QH is 3,6-dihydro-2H-pyridin-1,4-diyl.

[00365] In one embodiment, QH is 9-azaspiro[5.5]undecan-3,9-diyl.

[00366] In one embodiment, QH is 2-azaspiro[3,5]nonan-2,7-diyl.

[00367] In one embodiment, QH is morpholin-2,3-diyl.

[00368] In one embodiment, RJ is C1-3-alkyl.

[00369] In one embodiment, RJ is Me.

[00370] In one embodiment, RG is C1-3-alkyl.

[00371] In one modality, RG is H or Me.

[00372] In one modality, RG is Me.

[00373] In one modality, RG is H.

[00374] In one modality, the Ligand (e.g., 'a' -QA-QB-QC- 'b') is selected from any of the Ligands 1 to 58 shown below: Petition 870250080967, dated 09 / 09 / 2025, page 54 / 523 / 482 Petition 870250080967, dated 09 / 09 / 2025, page 55 / 523 / 482 Petition 870250080967, dated 09 / 09 / 2025, page 56 / 523 / 482 Petition 870250080967, dated 09 / 09 / 2025, p. 57 / 523 48 / 482

[00375] In one embodiment, the Ligand (for example, 'a' -QA-QB-QC'b') is selected from any of the Ligands 1, 3, 6, 9, 19, 28, 45, 47, 49, 50, 51, 52, 53, 54, 55, 56, 57 and 58.

[00376] In some forms, Ligand 54 is 54a: 54a

[00377] In one embodiment, W is a binding unit of the E3 ubiquitin ligase cereblon linked to the 'b' end of the Ligand through a C atom available in said binding unit of the E3 ubiquitin ligase cereblon.

[00378] In one embodiment, W is Wl, which is: -Z-(RA)h where Z is: given that: --77777 represents a single covalent bond or a double covalent bond; 0, 1 or 2 out of Xa, Xb, Xc, Xd, Xee XEé / are N, where XEe XEnão are not both N, and otherwise are C; among XG, XHe XJé C(O); among XG, XHe XJ is N-(2,6-dioxopiperidin-3-yl) (Y); and among XG, XHe XJ is selected from C(RT)2, -CH2CH2-, C(O), N(C1-3-alkyl), -O- and -N=, wherein each RT is selected from H, F, Me or together with the carbon of C(RT)2 form a cycloprop-1,1-di-yl group; Petition 870250080967, dated 09 / 09 / 2025, p. 58 / 523 / 482 in which XG, XH and XJ are selected so that there are no two C(O) groups present in adjacent positions and that the N-(2,6-dioxopiperidin-3-yl) is not in a position adjacent to N(C1-3-alkyl) or O; each Raé independently has a substituent on any available C atom in Xa, Xb, Xcou XD selected from F, Cl, C13alkyl, C1-3alkoxy, wherein said C1-3alkyl and Qqalkoxy are independently optionally substituted by one or more F; h is 0, 1, or 2; and the ligand is bonded to any C atom in Xa, Xb, Xcou XD.

[00379] Y is:

[00380] In one embodiment, 0 or 1 among Xa, Xb, Xc, Xd, Xee XFé N e, otherwise, are C.

[00381] In one embodiment, 1 or 2 of Xa, Xb, Xc, Xd, Xee XFé / are N and, otherwise, are C.

[00382] In one embodiment, Xa, Xb, Xc, Xd, Xee XF are all C.

[00383] In one embodiment, 1 among Xa, Xb, Xc, Xd, Xee XFé N e, otherwise, are C.

[00384] In one embodiment, 2 out of Xa, Xb, Xc, Xd, Xe and XF are N, where Xe and XF are not both N and, otherwise, are C.

[00385] In one embodiment, Xb, Xd and XF are all C, and 0, 1 or 2 among Xa, Xce XEé / são N e, na outra, são C. Petition 870250080967, dated 09 / 09 / 2025, page 59 / 523 / 482

[00386] In one embodiment, XB, XDe, and XF are all C, and 0, 1, or 2 are among Xa, Xc, and XE are N and otherwise C; wherein the ligand is linked to XB or Xa when Xa is C.

[00387] In one embodiment, XB, XD, and XF are all C, and 0, 1, or 2 of Xa, Xc, and XE are N and otherwise C; wherein the Ligand is linked to XB.

[00388] In one embodiment, XG-XH-XJ is: (i) Xg-NY-C(O), where XG is -CH2-, -CH2CH2-, =N- or C(O); (ii) Xg-C(O)-NY, wherein Xg is -O- or N(C1-3 alkyl) [e.g., N(Me)]; or (iii) C(O)-NY-CH2.

[00389] In one embodiment, the ligand is bonded to a C atom in Xaou XBe XG-XH-XJé: (i) Xg-NY-C(O), where XG is -CH2-, -CH2CH2-, =N- or C(O); (ii) Xg-C(O)-NY, wherein Xg is -O- or N(C1-3 alkyl) [e.g., N(Me)]; or (iii) C(O)-NY-CH2.

[00390] In one embodiment, the ligand is bonded to a C atom in XBe XG-XH-XJé: (i) Xg-NY-C(O), where XG is -CH2-, -CH2CH2-, =N- or C(O); (ii) Xg-C(O)-NY, wherein Xg is -O- or N(C1-3 alkyl) [e.g., N(Me)]; or (iii) C(O)-NY-CH2.

[00391] In one embodiment, XG-XH-XJé CH2-NY-C(O).

[00392] In one embodiment, XG-XH-XJé CH2CH2-NY-C(O).

[00393] In one embodiment, XG-XH-XJé =N-NY-C(O).

[00394] In one embodiment, XG-XH-XJé C(O)-NY-C(O).

[00395] In one form, XG-XH-XJé OC(O)-NY.

[00396] In one embodiment, XG-XH-XJ is N(C1-3alkyl)-C(O)-NY [for example, N(Me)-C(O)-NY]. Petition 870250080967, dated 09 / 09 / 2025, p. 60 / 523 / 482

[00397] In one embodiment, XG-XH-XJ is C(O)-NY-CH2.

[00398] In one embodiment, each RA is a substituent at any available C in Xa, Xb, Xcou XD selected from F, Cl and C1-3 alkoxy optionally substituted by one or more F.

[00399] In one embodiment, each RA is a substituent at any available C in Xa, Xb, Xcou XD selected from F, Cl, OMe and -OCHF2.

[00400] In one modality, h is 0.

[00401] In one modality, h is 1.

[00402] In one form, h is 2.

[00403] In one embodiment, the Ligand is linked to XC, where XC is C; and Xaé C linked to RA, where RAé OMe, in which the said methyl group is optionally replaced by one or more F groups (for example, -OCHF2).

[00404] In one embodiment, the Ligand is linked to XC, where XC is C; and Xaé C connected to RA, where RAé OMe or -OCHF2.

[00405] In one embodiment, -Z-(RA)h, together, represent any of the groups 1, 4, 16, 17 and 19 (with reference to the specific groups -Z-(RA)h 1 to 21 whose structures are presented below).

[00406] In one embodiment, h is 1 and RA is C1-3 alkoxy [e.g., OMe].

[00407] In one embodiment, h is 1 or 2, one RA is OMe and the other RA (when present, i.e., when h is 2) is Cl.

[00408] In one embodiment, h is 1 or 2, one RA is Cl and the other RA (when present, i.e., when h is 2) is OMe.

[00409] In one modality, h is 1 and RA is F.

[00410] In one embodiment, h is 1 and RA is Cl.

[00411] In one modality, h is 1 and RA is -OCHF2.

[00412] In one embodiment, the Ligand is linked to a C in Xaou XB, eh is 0. Petition 870250080967, dated 09 / 09 / 2025, p. 61 / 523 / 482

[00413] In one embodiment, the Ligand is attached to a C in Xaou XB, h is 1 and Ra is a substituent in Xc, where Xc is C and Ra is F.

[00414] In one embodiment, the Ligand is attached to a C in Xa or Xb, h is 1 and Ra is a substituent in Xd, where Xd is C and Ra is OMe or -OCHF2.

[00415] In one embodiment, the Ligand is attached to a C in Xb, h is 0, 1 or 2; the first Ra (when present, i.e., when h is 1 or 2) is a substituent on an available C in Xd and the second Ra (when present, i.e., when h is 2) is on an available C in Xa.

[00416] In one embodiment, the ligand is attached to a C in Xb, h is 0, 1 or 2; the first Ra (when present, i.e., when h is 1 or 2) is a substituent on an available C in Xd selected from Cl, OMe and -OCHF2; and the second Ra (when present, i.e., when h is 2) is on an available C in Xa and is selected from Cl and OMe.

[00417] In a modality -Z-(RA'”)h, together, represent any of the groups 1 to 21, 27 and 32 shown below: Petition 870250080967, dated 09 / 09 / 2025, p. 62 / 523 / 482 Petition 870250080967, dated 09 / 09 / 2025, p. 63 / 523 / 482

[00418] given that: ------- represents a single covalent bond or a double covalent bond; Among Xa2, XB2, XC2 and XD2, C is covalently bonded to YN; 0, 1 or 2 among Xa2, XB2, XC2, XD2, XE2 and XF2 are N (where XE2 and XE2 are not both N) and, otherwise, are C; or 2 out of XG2, XH2 and XJ2 are N; and otherwise, they are C; each RAA is a substituent on any available C or N atom of Z - in each case independently selected from RAA1 optionally substituted by one or more RAA2; wherein RAA is additionally selected from RAA2 when RAA is a substituent on an available C atom of ZA; each Raa1 is, independently, C1-alkyl, C2-3-alkenyl, C2-alkynyl, C1-alkoxyC1-qalkyl, carboxyC1-qalkyl, C5-v-carbocyclyl or a 4- to 6-membered heterocyclyl; Petition 870250080967, dated 09 / 09 / 2025, p. 64 / 523 / 482 each R^2 is independently selected from F, Cl, Br, CN, NH2, C1-3 alkyl, O(C1-3 alkyl), NH(C1-3 alkyl) and N(C1-3 alkyl)2; wherein said C1-3 alkyls are optionally replaced by one or more F; v is 0, 1 or 2; YN is 2,4-dioxo-hexahydropyrimidin-l-yl.

[00419] YNé:

[00420] In one modality, ZA is: given that: ------- represents a single covalent bond or a double covalent bond; Among Xa2e XB2e C and covalently bonded to YNe the other among Xa2e XB2e C; or 1 of XC2e XD2é N and, otherwise, é / são C; Among XG2 and XJ2, one is N and the other among XG2 and XJ2 is C; and XH2, XE2, and XF2 are all C.

[00421] In one embodiment, -ZA-YN, together, represent any one or more of the Al to A5 groups shown below, wherein, in each case, said ZA group is optionally substituted at the available C and / or N atom(s) by -[R^jv] as further defined herein. Petition 870250080967, dated 09 / 09 / 2025, p. 65 / 523 / 482

[00422] In one embodiment, each RAA is a substituent on any available C or N atom of ZA—in each case, independently selected from RAA1 optionally substituted by one or more RAA2; wherein RAA is additionally selected from RAA2 when RAA is a substituent on an available C atom of Z; wherein each RAA1 is independently C1-4 alkyl or a 4- to 6-membered heterocycline; and each RAA2 is independently selected from F, Cl, CN and C1-3 alkyl.

[00423] In one embodiment, each RAA is a substituent on any available C or N atom of ZA—in each case independently selected from RAA1 optionally substituted by one or more RAA2; wherein RAA is additionally selected from RAA2 when RAA is a substituent on an available C atom of ZA; wherein each RAA1 is independently methyl, isopropyl, cyclopropyl, pyridinyl or pyrazolyl; and each RAA2 is independently F, Cl, CN or methyl.

[00424] In one embodiment, each RAA is a substituent on an available C atom of ZA, each independently selected from methyl, isopropyl, cyclopropyl, pyridin-2-yl, 1-methylpyrazol-4-yl, -CH2CN, F, Cl, CN; and / or a methyl substituent on an available N atom of ZA.

[00425] In one modality, v is 0. Petition 870250080967, dated 09 / 09 / 2025, p. 66 / 523 / 482

[00426] In one form, v is 1.

[00427] In one form, v is 2.

[00428] In one modality, v is 1 or 2.

[00429] In one modality, v is 0 or 1.

[00430] In one embodiment, v is 1; XA1 is a C atom; and RAA is a substituent on XA1.

[00431] In one embodiment, v is 1; XA1 is a C atom; and RAA is a C1-4 alkyl substituent on XA1.

[00432] In one embodiment, v is 1; XB1 is a C atom; and RAA is a substituent on XB1.

[00433] In one embodiment, v is 1; XB1 is a C atom; and RAA is a C1-4 alkyl (e.g., methyl) substituent on XB1.

[00434] In one embodiment, v is 1; XC1 is a C atom; and RAA is a substituent on XC1.

[00435] In one embodiment, v is 1; XC1 is a C atom; and RAA is a C1-4 alkyl (e.g., methyl) substituent on XC1.

[00436] In one embodiment, v is 1; XD1 is a C atom; and RAA is a substitute in XD1.

[00437] In one embodiment, v is 1; XD1 is a C atom; and RAA is a C1-4 alkyl (e.g., methyl) or F substituent on XD1.

[00438] In one embodiment, v is 1; XG1 is a C atom; and RAA is a substituent on XG1.

[00439] In one embodiment, v is 1; XG1 is a C atom; and RAA is a substituent on XG1; wherein RAA is selected from RAA1 optionally substituted by one or more RAA2; or RAA is selected from RAA2; wherein RAA1 is C1-4 alkyl or a 4- to 6-membered heterocycline; and RAA2 is selected from F, Cl, CN and C1-3 alkyl. Petition 870250080967, dated 09 / 09 / 2025, p. 67 / 523 / 482

[00440] In one embodiment, v is 1; XG1 is a C atom; and RAA is a substituent on XG1; wherein RAA is selected from methyl, isopropyl, cyclopropyl, pyridine-2-yl, 1-methylpyrazol-4-yl, -CH2CN, F, Cl and CN.

[00441] In one embodiment, v is 1 or 2; XG1 is a C atom; and one or more RAA is a substituent on XG1; wherein RAA is selected from RAA1 optionally substituted by one or more RAA2; or RAA is selected from RAA2; wherein RAA1 is C1-4 alkyl or a 4- to 6-membered heterocycline; and RAA2 is selected from F, Cl, CN and C1-3 alkyl; and when v is 2, the additional RAA is a fluoro-substituted group on an available C atom of ZA.

[00442] In one embodiment, v is 1; XG1 is an N atom; and RAA is a substituent on XG1.

[00443] In one embodiment, v is 1; XG1 is an N atom; and RAA is a C1-4 alkyl (e.g., methyl) substituent on XG1.

[00444] In one embodiment, v is 1; XH1 is a C atom; and RAA is a substituent on XH1.

[00445] In one embodiment, v is 1; XH1 is a C atom; and RAA is a substituent on XH1 that is CN or C1-4 alkyl (e.g., methyl).

[00446] In one embodiment, v is 1 or 2; XH1 and XG1 are both C atoms, one or both of which are substituted by RAA, wherein each RAA is independently selected from CN or C1-4 alkyl (e.g., methyl).

[00447] In one modality, the group: together represents one or more of the groups A1 to A9, shown below: Petition 870250080967, dated 09 / 09 / 2025, p. 68 / 523 / 482 A7 A8 A9

[00448] In some of these modalities, W is W2-1 given that: XKe XLsão N-ligand and CH, N-ligand and CMe, or N-ligand and Cligand, respectively; among XMe Xo is C-2,4-dioxo-hexahydropyrimidin-1-yl (YN); or 1 of XMe XNé CF; XN can be N if XM is not CF; the remainder among XN, XMe Xoé CH; XPé CH or CMe. Petition 870250080967, dated 09 / 09 / 2025, p. 69 / 523 / 482

[00449] In a W modality, it represents any of the groups 22 to 26, 29, and 31 shown below:

[00450] -ZB In one modality, W is W3, which is: where ZB is: XE3 is selected from C(=O) and CRE1RE2, wherein RE1 and RE2 are independently selected from the group consisting of H and C1-3 alkyl, or RE1 and RE2, taken together with the carbons to which they are attached, form a C3-6 cycloalkane ring; Y is N-(2,6-dioxopiperidin-3-yl); all of Xa3, XB3, XC3 and XD3 are C; A pair of Xa3e XB3, XB3e XC3e XC3e XD3 forms a five- or six-membered heterocyclic ring containing fully unsaturated or partially unsaturated N, which is linked to the 'b' end of the ligand through an N atom; The others, including Xa3, XB3, XC3, and XD3, contain an RB group, where each RB is selected from H, F, Cl, C1-3 alkyl, and C1-3 alkoxy.

[00451] In one embodiment, XE3 is C(=O). Petition 870250080967, dated 09 / 09 / 2025, p. 70 / 523 / 482

[00452] In one embodiment, XE3 is CRE1RE2, wherein RE1 and RE2 are independently selected from the group consisting of H and C1-3 alkyl, or RE1 and RE2, taken together with the carbons to which they are attached, form a C3-6 cycloalkane ring.

[00453] In one embodiment, XE3 is CRE1RE2, wherein RE1 and RE2 are independently selected from the group consisting of H and C1-3 alkyl, such as methyl.

[00454] In one embodiment, Xa3e XB3 form a five- or six-membered heterocyclic ring containing fully unsaturated or partially unsaturated N, which is linked to the 'b' end of the ligand through an N atom.

[00455] In one embodiment, XB3 and XC3 form a five- or six-membered heterocyclic ring containing fully unsaturated or partially unsaturated N, which is linked to the 'b' end of the ligand through an N atom.

[00456] In one embodiment, XC3 and XD3 form a five- or six-membered heterocyclic ring containing fully unsaturated or partially unsaturated N, which is linked to the 'b' end of the ligand through an N atom.

[00457] In one embodiment, the five- or six-membered fully unsaturated or partially unsaturated N-containing heterocyclic ring is a five-membered ring in which there is no additional unsaturation.

[00458] In one embodiment, each RB is selected from H, F, Cl, methyl, and methoxy.

[00459] In one modality, each RBé H.

[00460] In one modality, W is group 28: Petition 870250080967, dated 09 / 09 / 2025, page 71 / 523 / 482

[00461] In one modality, W is W4, which is: -ZC where ZCé: One of XB4e XC4e is CC(=O)-NH-Y; One of Xa4, XB4, Xc4, XD4, and XE4 can be CF; or One or two of Xa4, XB4, Xc4, XD4 and XE4 can be N; The remainder among Xa4, XB4, Xc4, XD4 and XE4 is CH.

[00462] In one modality, one of Xa4, XB4, Xc4, XD4 and XE4 is CF.

[00463] In one modality, XB4 is CF.

[00464] In one embodiment, one of XB4 is CF and XC4 is CC(=O)NH-Y.

[00465] In one modality, two of Xa4, XB4, Xc4, XD4 and XE4 are N.

[00466] In one modality, one of Xa4, XB4, Xc4, XD4 and XE4 is N.

[00467] In one modality, none of Xa4, XB4, Xc4, XD4 and XE4 is N.

[00468] In one modality, none of Xa4, XB4, Xc4, XD4 and XE4 is N, and one of Xa4, XB4, Xc4, XD4 and XE4 is CF.

[00469] In one embodiment, XB4 is CF, XC4 is CC(=O)-NH-Y and Xa4, XD4 and XE4 are CH.

[00470] In one modality, W is group 30: Petition 870250080967, dated 09 / 09 / 2025, p. 72 / 523 / 482

[00471] In a further aspect of the descriptive report, formula (Ia) is selected from any one or more of the following groups (1) to (43): (1) 4-[1-(4-chloro-3-cyano-1H-indol-7-yl)-4-piperidyl]phenyl; (2) 4-[1-(3-cyano-4-fluoro-1H-indol-7-yl)-4-piperidyl]phenyl; (3) 4-[1-(3-cyano-4-methyl-1H-indol-7-yl)-4-piperidyl]phenyl; (4) 4-[1-(4-chloro-3-cyano-1H-indazol-7-yl)-3-piperidyl]phenyl; (5) 4-[1-(4-chloro-3-cyano-1H-indol-7-yl)-3-piperidyl]phenyl; (6) 4-[1-(3-cyano-4-fluoro-1H-indol-7-yl)-3-piperidyl]phenyl; (7) 4-[1-(3-cyano-4-methyl-1H-indol-7-yl)-4-piperidyl]-3-fluorophenyl; (8) 4-[1-(3-cyano-1H-indol-7-yl)-4-piperidyl]phenyl; (9) 6-[1-(4-chloro-3-cyano-1H-indol-7-yl)-4-piperidyl]-3-pyridyl; (10) 5-[1-(4-chloro-3-cyano-1H-indol-7-yl)-4-piperidyl]pyrazin-2yla; (11) 4-[3-(3-cyano-4-methyl-1H-indol-7-yl)-1-piperidyl]phenyl; (12) 3-[3-(3-cyano-4-methyl-1H-indol-7-yl)-1-piperidyl]phenyl; (13) 4-[3-(4-chloro-3-cyano-1H-indol-7-yl)-1-piperidyl]phenyl; (14) 4-[4-(3-cyano-4-methyl-1H-indol-7-yl)piperazin-1-yl]phenyl; (15) 5-[1-(4-chloro-3-cyano-1H-indol-7-yl)-4-piperidyl]-2pyridyl; (16) 4-[1-(4-chloro-3-cyano-1 -methyl-indol-7-yl)-4-piperidyl]phenyl; (17) 3-[1-(4-chloro-3-cyano-1H-indol-7-yl)-4-piperidyl]phenyl; (18) 5-[1-(4-chloro-3-cyano-1H-indol-7-yl)-3-piperidyl]-2pyridyl; (19) 4-[4-(4-chloro-3-cyano-1H-indol-7-yl)morpholin-2-yl]phenyl; (20) 4-[4-(4-chloro-3-cyano-1H-indazol-7-yl)morpholin-2yl]phenyl; Petition 870250080967, 09 / 09 / 2025, pág. 73 / 523 / 482 (21) 6-[1-(4-chloro-3-cyano-1H-indol-7-yl)-3-piperidyl]pyridazin3-yl; (22) 4-[1-(3-cyano-4-fluoro-1H-indazol-7-yl)-3-piperidyl]phenyl; (23) 4-[1-(4-chloro-3-cyano-1H-indazol-7-yl)-4-piperidyl]phenyl; (24) 4-[1-(3-cyano-4-fluoro-1H-indazol-7-yl)-4-piperidyl]phenyl; (25) 4-[1-(3-cyano-4-methyl-1H-indazol-7-yl)-4-piperidyl]phenyl; (26) 4-[1-(3-cyano-4-methyl-1H-indol-7-yl)pyrrolidin-3-yl]phenyla; (27) 4-[[1-(4-chloro-3-cyano-1H-indazol-7-yl)-4piperidyl]carbamoyl]-3-fluoro-phenyl; (28) 4-[[1-(4-chloro-3-cyano-1H-indol-7-yl)-4piperidyl]carbamoyl]-3-fluoro-phenyl; (29) 4-[[1-(4-chloro-3-cyano-1H-indol-7-yl)-4piperidyl]carbamoyl]-3-cyano-phenyl; (30) 4-[[1-(4-chloro-3-cyano-1H-indol-7-yl)-4piperidyl]carbamoyl]-3-fluoro-5-methyl-phenyl; (31) 4-[[1-(4-chloro-3-cyano-1H-indol-7-yl)-4piperidyl]carbamoyl]-2-methyl-phenyl; (32) 4-[[1-(4-chloro-3-cyano-1H-indol-7-yl)-4piperidyl]carbamoyl]-2-cyano-phenyl; (33) 6-[[1-(4-chloro-3-cyano-1H-indol-7-yl)-4piperidyl]carbamoyl]-3-pyridyl; (34) 6-[[1-(4-chloro-3-cyano-1H-indazol-7-yl)-4piperidyl]carbamoyl]-3-pyridyl; (35) 6-[[1-(3-cyano-4-methyl-1H-indol-7-yl)-4piperidyl]carbamoyl]-3-pyridyl; (36) 4-[[1-(4-chloro-3-cyano-1H-indol-7-yl)-4piperidyl]carbamoyl]phenyl; (37) 4-[[4-(4-chloro-3-cyano-1H-indol-7-yl)cyclohexyl]carbamoyl]-3-fluoro-phenyl; Petition 870250080967, 09 / 09 / 2025, pág. 74 / 523 / 482 (38) 4-[[1-(4-chloro-3-cyano-1H-indol-7-yl)-4piperidyl]carbamoyl]-3,5-difluoro-phenyl; (39) piperidyl]carbamoyl]pyrazin-2-yl; (40) piperidyl]carbamoyl]pyrimidin-5-yl; (41) piperidyl]carbamoyl]-3-methyl-phenyl; (42) piperidyl]carbamoyl]pyridazin-3-yl; 5-[[1-(4-chloro-3-cyano-1H-indol-7-yl)-42-[[1-(4-chloro-3-cyano-1H-indol-7-yl)-44- [[1-(4-chloro-3-cyano-1H-indol-7-yl)-46-[[1-(4-chloro-3-cyano-1H-indol-7-yl)-4(43) 6-[[(3R)-1-(4-chloro-3-cyano-1H-indol-7-yl)-3piperidyl]carbamoyl]-3-pyridyl.

[00472] In a further aspect of the descriptive report, a PROTAC compound or a pharmaceutically acceptable salt thereof is provided, containing an E3 ubiquitin ligase cereblon binding unit and an AR binding unit of formula (Ia) or formula (Ib): _i Praça (Ib) where: QA is -G-QH- or -G-(C1-5alkylene)-; G is a direct linkage, -CH2-, -C(=O)-, -O- or -N(RG)-, where each R is independently H or C1-3 alkyl; QH is a saturated or partially unsaturated heterocyclic group containing nitrogen with 4 to 12 members; Petition 870250080967, dated 09 / 09 / 2025, p. 75 / 523 / 482 and where R1, p, X1, RN, n, m, R2a, R2b, Q1, Q2, Q3, Q4, Y1, Y2, Y3, Y4, Y5, R3 and q can assume any of the values ​​defined here for each of these groups / variables, respectively.

[00473] In one embodiment, QH is a saturated heterocyclic group containing nitrogen with 4 to 12 members.

[00474] To avoid doubts in the formula (Ib) indicates a connection point through a single covalent bond to the rest of the PROTAC compound.

[00475] In a further aspect of the descriptive report, a PROTAC compound or a pharmaceutically acceptable salt thereof is provided, containing an E3 ubiquitin ligase cereblon binder unit linked to an AR-binding unit of formula (Ia) or formula (Ib), as defined herein.

[00476] In other forms of this descriptive report, formula (Ib) may be: LX—QA-| where Lx can be any of the groups (1) to (43) mentioned above in conjunction with formula (Ia); and where QA can assume any value(s) revealed here for QA.

[00477] In a further aspect of the descriptive report, a PROTAC compound or a pharmaceutically acceptable salt thereof is provided, containing an E3 ubiquitin ligase cereblon binder unit and an AR-binding unit of formula (Ia) or formula (Ic): Petition 870250080967, dated 09 / 09 / 2025, p. 76 / 523 / 482 (Ic) in which: QA is -G-QH- or -G-(C1-5alkylene)-; G is a direct linkage, -CH2-, -C(=O)-, -O- or -N(RG)-, where RG is H or C1-3 alkyl; QB is a direct linkage, -QB1-QB2-QB3- or C1-3 alkylene optionally substituted by one or more F groups (e.g., 1 or 2); wherein: QB1 and qB3 each independently represent a direct or C1-2 alkylene bond; QB2 is QH, -O-CH2CH2-O-, -O- or -N(RJ)-, where RJ is H or C1-3 alkyl; and each QHé is, independently, a saturated or partially unsaturated heterocyclic group containing nitrogen with 4 to 12 members; where the QAe QB values ​​are selected so that formula (Ic) does not contain any NN or NO bonds; and where R1, p, X1, RN, n, m, R2a, R2b, Q1, Q2, Q3, Q4, Y1, Y2, Y3, Y4, Y5, R3 and q can otherwise assume any of the values ​​defined here for each of these groups / variables, respectively.

[00478] In one embodiment, QH is a saturated heterocyclic group containing nitrogen with 4 to 12 members. For the avoidance of doubt, ^c in formula (Ic) indicates a point of connection via a single covalent bond to the rest of the compound PROTAC. Petition 870250080967, dated 09 / 09 / 2025, page 77 / 523 68 / 482

[00479] In a further aspect of the descriptive report, a PROTAC compound or a pharmaceutically acceptable salt thereof is provided, containing an E3 ubiquitin ligase cereblon binder unit linked to an AR-binding unit of formula (Ia) or formula (Ic), as defined herein.

[00480] In other forms of this descriptive report, formula (Ib) may be: L—Q—Q— where Lx can be any of the groups (1) to (43) mentioned above in conjunction with formula (Ia); and where QA and QB can assume any value revealed here for QA and QB.

[00481] In other embodiments, pharmaceutically acceptable compound(s) or salt(s) thereof are provided, wherein said compound(s) is / are selected from one or more of the Examples mentioned below. Thus, these embodiments include one or more specific Examples (for example, one Example, or two or three specific Examples) selected from the group consisting of Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 153, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180 and 181. Petition 870250080967, dated 09 / 09 / 2025, p. 78 / 523 / 482

[00482] It should be understood that the compound in an Example mentioned below refers to the name of the compound in the title and is in no way limited by the method of preparation, nor by whether a given compound was isolated in the form of a salt and not as a neutral molecule.

[00483] In some embodiments, a compound of formula (VI) is provided: (VI) or a pharmaceutically acceptable salt thereof, where: X11 is CH or N; R11 is F, Cl or Me; Q11 and Q12 are N and CH or CH and N, respectively; They are neither 1 and 1 nor 2 and 0, respectively; Q14 is a single bond or -NHC(=O); Y11 and Y12 are selected from CH and CH, CF and CH, N and CH, and N and N, respectively; The ligand is selected from among ligands 3, 47, 49, 54, and 58: Petition 870250080967, dated 09 / 09 / 2025, p. 79 / 523 / 482

[00484] W is selected from groups 1, 2, 3, 15, 16, 22, 24, 25, 26, 28, 31 and 32: , where Y is 2,6-dioxopiperidin-3-yl and YN is 2,4-dioxo-hexahydropyrimidin-1-yl.

[00485] In some embodiments, a compound of formula (VI-1) is provided: Petition 870250080967, dated 09 / 09 / 2025, p. 80 / 523 71 / 482 (VI-1) or a pharmaceutically acceptable salt thereof, provided that: X21 is CH or N; R21 is F and Cl; They are neither 1 and 1 nor 2 and 0, respectively; The ligand is selected from among ligands 3 and 47:

[00486] and W is selected from groups 2, 22, and 24: , where Y is 2,6-dioxopiperidin-3-yl and YN is 2,4-dioxo-hexahydropyrimidin-1-yl.

[00487] (VI-2): In some embodiments, a compound of formula (VI-2) or a pharmaceutically acceptable salt thereof. Petition 870250080967, dated 09 / 09 / 2025, p. 81 / 523 / 482, where: X31 is CH or N; R31 is F, Cl and methyl; They are neither 1 and 1 nor 2 and 0, respectively; Q31 and Q32 are N and CH or CH and N, respectively; Q34 is a single bond or -NHC(=O); Y31eγ32s£0 selected from CH and CH, CF and CH, N and CH, and N and N, respectively; The ligand is selected from among ligands 3, 47, 49, 54, and 58:

[00488] W is selected from groups 1, 2, 3, 15, 16, 22, 24, 25, 26, 28, and 32: Petition 870250080967, dated 09 / 09 / 2025, p. 82 / 523 / 482 , where Y is 2,6-dioxopiperidin-3-yl and YN is 2,4-dioxo-hexahydropyrimidin-1-yl.

[00489] In some embodiments, a compound of formula (VII) is provided: (VII) or a pharmaceutically acceptable salt thereof, provided that: The ligand is a saturated or partially or completely unsaturated structure comprising C and H atoms and at least one heteroatom, said structure having terminal bonding points 'a4e' and 'b' and a minimum length of 5 to 26 atoms between 'a' and 'b'; said structure may include one or more linear and / or branched chains and / or rings and is Petition 870250080967, dated 09 / 09 / 2025, p. 83 / 523 / 482 optionally replaced in any available C atom(s) by one or more F; and W is a binding unit of the E3 ubiquitin ligase cereblon.

[00490] In some embodiments, a compound of formula (VII-I) is provided: (VII-I) or a pharmaceutically acceptable salt thereof, provided that: The ligand is selected from among ligands 3, 47, 49, 54, and 58:

[00491] W is selected from groups 1, 2, 3, 15, 16, 22, 24, 25, 26, 28, 31 and 32: Petition 870250080967, dated 09 / 09 / 2025, p. 84 / 523 / 482 , where Y is 2,6-dioxopiperidin-3-yl and YN is 2,4-dioxo-hexahydropyrimidin-1-yl.

[00492] In some embodiments, a compound of formula (VII-II) is provided: Petition 870250080967, dated 09 / 09 / 2025, p. 85 / 523 / 482 (VII-II) or a pharmaceutically acceptable salt thereof, wherein: The ligand is selected from among ligands 3 and 47:

[00493] W is selected from groups 2, 22 and 24: , where Y is 2,6-dioxopiperidin-3-yl and YN is 2,4-dioxo-hexahydropyrimidin-1-yl.

[00494] In some embodiments, a compound of formula (VII-III) is provided: Petition 870250080967, dated 09 / 09 / 2025, p. 86 / 523 / 482 or a pharmaceutically acceptable salt thereof, wherein: The ligand is selected from among ligands 3, 47, 49, 54, and 58: and

[00495] W is selected from groups 1, 2, 3, 15, 16, 22, 24, 25, 26, 28, 31 and 32: Petition 870250080967, dated 09 / 09 / 2025, p. 87 / 523 78 / 482 , where Y is 2,6-dioxopiperidin-3-yl and YN is 2,4-dioxo-hexahydropyrimidin-1-yl.

[00496] In some embodiments, a compound of formula (VIII) is provided: NC (VIII) or a pharmaceutically acceptable salt thereof, Petition 870250080967, dated 09 / 09 / 2025, p. 88 / 523 / 482, where: W is a binding unit of the E3 ubiquitin ligase cereblon.

[00497] In some embodiments, a compound of the formula (VIII-I) is provided: NC (VIII-I) or a pharmaceutically acceptable salt thereof, wherein:

[00498] W is selected from groups 1, 2, 3, 15, 16, 22, 24, 25, 26, 28, 31 and 32: Petition 870250080967, dated 09 / 09 / 2025, p. 89 / 523 80 / 482 γ, where Υ is 2,6-dioxopiperidin-3-yl and YN is 2,4-dioxohexahydropyrimidin-1-yl.

[00499] In some embodiments, a compound of the formula (VIII-II) is provided: (VIII-II) or a pharmaceutically acceptable salt of the same, being:

[00500] W e selected from groups 2, 22, and 24: Petition 870250080967, dated 09 / 09 / 2025, p. 90 / 523 81 / 482 , where Y is 2,6-dioxopiperidin-3-yl and YNé is 2,4-dioxo-hexahydropyrimidine-1 -yl.

[00501] Specific compounds of this disclosure include: 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-l-oxo-2,3di-hydro-1 / / -isoindol-5 -yl]piperazine-1 -yl} methyl)piperidin-1 -yl-yl] phenyl / f-yl)piperidine1 -carbonytrile; 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-l-oxo-2,3-di-hydrol / 7-isoindole-5-yl]piperazine-l-yl}methyl)piperidin-l-yl]phenyl}piperidin-l-yl)- / 3-fluoro-ibonitril-l 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-l-oxo-2,3-di-hydrol / 7-isoindole-5-yl]piperazine-l-yl}methyl)piperidin-l-yl]phenyl}piperidin-l-yl)- / 3-fluoro-ibonitril-l 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-l-oxo-2,3-di-hydrol / 7-isoindol-5-yl]piperazine-l-yl}methyl)piperidin-l-yl]phenyl}piperidin-l-yl l-l-;3-fluoro-i-fluoro-; 4-chloro-7-(4- {4 - [4-( {4-[4-(2,4-dioxo-1,3-diazinan-1 -yl)-1 / 7indol-1 -yl]piperidin-1 -yl} methyl)piperidin-1 -yl] phenyl} piperidin-l-1 / 7 -itrindol-yl) 7-(4- {4- [4-( {4- [4-(2,4-dioxo-1,3-diazinan-1 -yl)- 1 / 7-indol-1 il]piperidine-1 -yl} methyl)piperidin-1 -yl]phenyl}piperidin-1 -yl)-13-7-fluoroindo- 4-chloro-7-(4- {4-[4-( {4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy1 -oxo-2,3 -di-hydro- l / 7-isoindole-5-yl]piperazine-1 -yl} methyl)piperidin-1 il]phenyl}piperidine-l-yl)-l / 7-indol-3-carbonitrile; Petition 870250080967, dated 09 / 09 / 2025, p. 91 / 523 / 482 7-(4-{4- [4-({4- [4-(2,4-dioxo-1-yl)-1 H-indol-1yl]piperidine-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-4-methyl-1 H-indole;3carbonitrile 4-chloro-7-[(3 5)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)1H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl] -1Hindazol-3 -carbonitrila; 4-chloro-7-[(3 S>3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1oxo-2,3-di-hidro-1 H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1yl]phenyl}piperidin-1-yl]-1 H-indazol-3-carbonitrila; 4-chloro-7-[(3 5)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)1H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl] -1Hindol-3-carbonitrila; 4-chloro-7-[(3 S>3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1oxo-2,3-di-hidro-1 H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1yl]phenyl}piperidin-1-yl]-1 H-indol-3-carbonitrila; 4-chloro-7-[(3 S)-3-{4-[4-({4-[6-(2,4-dioxo-1,3-diazinan-1-yl)-1methyl-1 H-indol-2-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl]1H-indol-3-carbonitrila; 4-chloro-7-[(3 5)-3-{4-[4-({4-[6-(2,4-dioxo-1,3-diazinan-1-yl)-1methyl-1H-indole-2-yl]piperidine-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-13-H-carnitrile-yl] 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1yl]phenyl}piperidin H-4-imethryl-yl-1)- 4-chloro-7-[4-(4-{4-[(4-{2-[(3 R *)-2,6-dioxopiperidin-3-yl]-7methoxy-1-oxo-2,3-di-hydro-1 H-isoindole-5-yl}piperazine- 1-yl)methyl]piperidinyl-1-]piperidin-]piperidin} H-indole-3-carbonitrile; Petition 870250080967, dated 09 / 09 / 2025, p. 92 / 523 / 482 4-chloro-7-[4-(4-{4-[(4-{2-[(3 5 *)-2,6-dioxopiperidin-3-yl]-7methoxy-1-oxo-2,3-di-hydro-1 H-isoindole-5-yl}piperazine- 1-yl)methyl-methyl1-piperidine]piperidine-]piperidine-1 H-indole-3-carbonitrile; 4-chloro-7-[4-(4-{4-[(4-{2-[(3 R *)-2,6-dioxopiperidin-3-yl]-1oxo-2,3-di-hydro-1 H-isoindol-5-yl}piperazin-1-yl)methyl]piperidin-1yl}H-phenyl-1-indotrilpiperidine-1; 4-chloro-7-[4-(4-{4-[(4-{2-[(3 S *)-2,6-dioxopiperidin-3-yl]-1oxo-2,3-di-hydro-1 H-isoindol-5-yl}piperazine-1-yl)methyl]piperidine-1yl}H-phenyl-1-indotrilpiperidine-1; 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1yl]phenyl} piperidin-13-14-luoro-yl) -carbonytrile; 4-chloro-7-[(3 R )-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1oxo-2,3-di-hydro-1 H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1yl]H-phenyl}ylpiperilane-1;3 7-(4-{4- [4-({1- [2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperidin-4-yl}methyl)piperazine-1-yl]phenyl}piperidin-1-yl-la)-1-4carbonyfluoro- 7-[(3 S)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl]-4-fluoro-fluoro-3-carindole 7-[(3 S)-3-{4-[4-({4-[2-(2,6-dioxopiperidine-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl} methyl)piperidin-1-yl]phenyl}piperidin-fluindoryl]-1-4 4-chloro-7-[(3 R )-3-{4-[4-({4-[4-(2,4-dioxo- 1,3-diazinan-1-yl)1H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-carbon] -1 Petition 870250080967, dated 09 / 09 / 2025, p. 93 / 523 / 482 4-chloro-7-[(3 R )-3-{4-[4-({4-[4-(2,4-dioxo- 1,3-diazinan-1-yl)1H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-caronitrile] -3 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-1-yl}-4carbonyl-la H1; 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-1-yl}-4-methyl-1H-carbonitrilel; 7-{4-[4-(4-{4-[4-(2,4-dioxo-1,3-diazinan-1 -yl)-1 H-indol-1yl]piperidin-1-yl}butoxy)phenyl]piperidin-1-yl}-4-methyl-1 H-indol-3 -carbonitrile; 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy-3-oxo2,3-di-hydro-1 H-pyrrole[3,4-c]pyridine-6-yl]piperazine-1-yl}methyl)piperidine-piperidin-1-pyryl-1-methyl-phenyl] H-indol- 3-carbonitrile; 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy-3-oxo2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperazine-1yl}butoxy)phenyl]piperidin-1-4-methyl} H-indole-3-carbonitrile; 4-chloro-7-{4-[4-(4-{4-[2-(2,6-dioxopiperidine-3-yl)-4-methoxy-3oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperazine-1yl}butoxy-)H-phenyl-indotril}pyridine; 7-{4-[4-(4-{4-[4-(2,4-dioxo-1,3-diazinan-1 -yl)-1 H-indol-1yl]piperidin-1-yl}butoxy)phenyl]piperidin-1-yl}-4-fluoro-1 H-indol-3 -carbonitrile; 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperazine-1yl}methyl)pyperidin-1}]piperidin-1-1 H-indole-3 -carbonitrile; 4-chloro-7-[4-(4-{4-[(4-{2-[(3 R *)-2,6-dioxopiperidin-3-yl]-4methoxy-3-oxo-2,3-di-hydro-1 H-pyrrolo[3,4-c]pyridine-6-yl}piperazine-1yl)methyl]piperidin-1-yl}phenyl)piperidin-1-yl]-1H-indole-3-carbonitrile; Petition 870250080967, dated 09 / 09 / 2025, p. 94 / 523 / 482 4-chloro-7-[4-(4-{4-[(4-{2-[(3 S *)-2,6-dioxopiperidin-3-yl]-4methoxy-3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl)piperazine-pyperil}phenyl-methyl] 1-yl]-1 H-indole-3-carbonitrile; 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidine-3-yl)-4-methoxy-3-oxo2,3-di-hydro-1 H-pyrrole[3,4-c]pyridine-6-yl]piperazine-1-yl}methyl)piperidinyl gold-piperil-1-4-f-phenyl] H-indole-3 -carbonitrile; 4-chloro-7-[(3 S)-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4methoxy-3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperazine-1pheryln}methyl)piperazine -yl]-1 H-indole-3 -carbonitrile; 4-chloro-7-[(3 S)-3-(4-{4-[(4-{2-[(3 R *)-2,6-dioxopiperidin-3yl]-4-methoxy-3 -oxo-2,3-di-hydro-1 H-pyrrole [3,4-c]pyridin-6-pyryl}dinethyl-piperazine] -yl}phenyl)piperidine- 1-yl]-1 H-indole-3-carbonitrile; 4-chloro-7-[(3 S)-3-(4-{4-[(4-{2-[(3 S *)-2,6-dioxopiperidine-3-yl]4-methoxy-3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-ylperil}piperamethyl)piperamethyl1]-1 -yl}phenyl)piperidine- 1-yl]-1 H-indole-3-carbonitrile; 7-(4-{4- [4-({4- [2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1-yl]-2fluorophenyl-1methyl-4-pyridin) H-indole-3-carbonitrile; 7-(4-{4- [4-({4- [4-(2,4-dioxo-1-yl)-1 H-indol-1yl]piperidin-1-yl}methyl)piperidin-1-yl]-2-fluorophenyl} piperidin- 1-yl)-4-tribonil-3H-indole 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1,3dioxo-2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1-yl]-2-perifluoro-methyl-yl}pi H-indole-3-carbonitrile; 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidine-3-yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-1-yl}-4-fluoro-carbon Hyndotrile;3-3-4 Petition 870250080967, dated 09 / 09 / 2025, p. 95 / 523 / 482 4-chloro-7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin- 1-yl}-car Hindotrile;3 4-chloro-7-{4-[4-(4-{4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}butoxy)phenyl]piperidin-1-yl}-1H-indol-3-carbonitrile; 4-chloro-7-[(3 R )-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4methoxy-3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperazin-1pherydin-1perinyl}-methyl)piperazine -yl]-1 H-indole-3 -carbonitrile; 7-{4-[4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1,3-dioxo2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]piperidine-1-yl};-4carbonyl-1 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy1,3-dioxo-2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1-peridin-1]phenyl}pi H-indole-3-carbonitrile; 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]lapiperidine-1-yl};-4carbonitril-1 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6-fluoro1,3-dioxo-2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1-peridin-1]phenyl}pi H-indole-3-carbonitrile; 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1yl]phenyl}piperiro)-1-4-flu-yl-yl H-indole-3-carbonitrile; 4-chloro-7-[(3 5)-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6fluoro-1,3-dioxo-2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}methyl-1-piperil1-pidine]-yl H-indole-3 -carbonitrile; 4-chloro-7-[(3 R )-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6fluoro-1,3-dioxo-2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piphenyl-iperidindol]-1-yl] -carbonytrile; Petition 870250080967, dated 09 / 09 / 2025, p. 96 / 523 / 482 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxo2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1yl]phenyl}piperidin-1; H-1-yl-indo) 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxo-2,3-dihydro-1 H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-1 -yl}-4-methyl-3-1 Hyndotrile; 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-1-yl}-1 H-indol-3carbonitrile; 7-{4-[4-(4-{4-[4-(2,4-dioxo-1,3-diazinan-1 -yl)-1 H-indol-1yl]piperidin-1-yl}butoxy)phenyl]piperidin-1-yl}-1 H-indol-3-carbonitrile; 7-(4-{4- [4-({4- [4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-1 H-indol-3carbonitrile; 4-chloro-7-(4-{5-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy1-oxo-2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1yl]piperidine-1-2-yl H-indole-3-carbonitrile; 4-chloro-7-(4-{5-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperazine-1yl}methyl-1-yl}piperidin-2) H-indol- 3-carbonitrile; 4-chloro-7-(4-{5-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]pyridin-2-yl}piperidin-1-yl)-1Hycarbonitrile-3; 4-chloro-7-(4-{ 6-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidine-1-yl}methyl)piperidin-1-yl]pyridazine-3-yl}piperidin-1-yl-la)-1 Hindol 4-chloro-7-(4-{6-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1-yl]pyridazin-3-1-ylbonytripyridine-1; Petition 870250080967, dated 09 / 09 / 2025, p. 97 / 523 / 482 4-chloro-7-[(3 R *)-3-{5-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)1H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1-yl]pyridin-2-yl}piperil-1-H-1-yl]indo 4-chloro-7-[(3 S*)-3-{5-[4-({4-[4-(2,4-dioxo- 1,3-diazinan-1-yl)1H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1-yl]pyridine-2-ylbonyl}piperidine-3-1-H 4-chloro-7-(4-{5-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidine-1-yl}methyl)piperidin-1-yl]pyrazine-2-yl}piperidin-1-yl-la);-3-Hycarbonitrile 4-chloro-7-(4-{5-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1-yl]pyrazine-2-1-ylbonindotril)pyridin-1; 7-[4-(4-{4-[(4-{[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3di-hydro-1H-benzimidazol-4-yl]methyl}piperazine-1-yl)methyl]piperidine-1yl}phenyl-1methyl-]piperidine H-indole-3-carbonitrile; 4-chloro-7-[4-(4-{4-[(4-{[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2oxo-2,3-di-hydro-1 H-benzimidazole-4-yl]methyl}piperazine-1-yl)methyl]piperidin-3)piperil-1-phenyl-phenyl -carbonytrile; 7-[4-(4-{4-[(4-{[[1-(2,6-dioxopiperidin-3-yl))-3-methyl-2-oxo-2,3di-hydro-1H-benzymidazol-4-yl]methyl}piperazine-1-yl)methyl]piperidin-1yl}phenyl H-3-4lpindoperidin-4 -carbonytrile; 4-chloro-7-(4-{4-[4-({4-[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2oxo-2,3-di-hydro-1 H-benzimidazol-4-yl]piperazine-1-yl}methyl)piperidin-1yl-1]H-3-phenyl-indoperidine- 4-chloro-7-[(3 S)-3-(4-{4-[(4-{[1-(2,6-dioxopiperidin-3-yl)-3methyl-2-oxo-2,3-di-hydro-1H-benzymidazol-4-yl]methyl}piperazine-1yl)methyl]piperidin-1-yl}car-H-phenyl)ylpiperidine-1;1 Petition 870250080967, dated 09 / 09 / 2025, p. 98 / 523 / 482 7-[(3 S)-3-(4-{4-[(4-{[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2oxo-2,3-di-hidro-1 H-benzimidazol-4-yl]methyl}piperazin-1-yl)methyl]piperidin1-yl}phenyl)piperidin-1-yl]-4-fluoro-1 H-indol-3-carbonitrila; 4-chloro-7-{4-[4-(4-{[6-(2,6-dioxopiperidin-3-yl)-5,7-dioxo3,5,6,7-tetra-hydropyrrolo[3,4-f]isoindol-2(1 H)-yl]methyl}piperidin-1yl)phenyl]piperidin-1-yl}-1H-indol-3-carbonitrila; 4-chloro-7-{(3 S)-3-[4-(4-{[6-(2,6-dioxopiperidin-3-yl)-5,7dioxo-3,5,6,7-tetra-hydropyrrolo[3,4-f]isoindol-2(1 H)-yl]methyl}piperidin-1yl)phenyl]piperidin-1-yl}-1H-indazol-3-carbonitrila; 4-chloro-7-{(3 S)-3-[4-(4-{[6-(2,6-dioxopiperidin-3-yl)-5,7dioxo-3,5,6,7-tetra-hydropyrrolo[3,4-f]isoindol-2(1 H)-yl]methyl}piperidin-1yl)phenyl]piperidin-1-yl}-1H-indol-3-carbonitrila; 7-{(3 R *)-1-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazin-1-yl}butoxy)phenyl]piperidin-3 -yl}-4-methyl-1 Hindol-3-carbonitrila; 7-{(3 S*)-1-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-3 -ylcar}-Hybontril-4-methyl;3-1-1 7-{(3 R *)-1-[3-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-3 -ylcar}-Hybontril-4-methyl;3-1-1 7-{(3 S *)-1-[3-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-3 -ylcar}-Hybontril-4-methyl;3-1-1 7-[(3 R *)-1-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3di-hydro-1 H-isoindol-5-yl]piperazine-1-yl} methyl)piperidin-1-yl]phenyl}piperin-4-carbonyndoyl-1-yl]- Petition 870250080967, dated 09 / 09 / 2025, p. 99 / 523 / 482 7-[(3 S*)-1-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3di-hydro-1 H-isoindol-5-yl]piperazine-1-yl} methyl)piperidin-1-yl]phenyl}piperin-4-carbonyndoyl-1-yl]- 4-chloro-7-(4-{4-[4-({4-[6-(2,4-dioxo-1,3-diazinan-1-yl)-1methyl-1H-indole-2-yl]piperidine-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl-la);1H-carbonitrile 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3di-hydro-1 H-isoindol-5-yl]piperazine-1-yl} methyl)piperidin-1 carbonyl]phenyl}piperidin-13;1-carbonil-yl) 4-chloro-7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy-3oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperazine-1-yl}piperidin-]piperidin-}1-phenyl) H-indole-3-carbonitrile; 4-chloro-7-(4-{4-[4-(2-{4-[2-(2,6-dioxopiperidin-3-yl)-4methoxy-3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridine-6-yl]piperazine-1yl-ethyl}pi-}pyridin-)piperidinl]piperidine H-indole-3-carbonitrile; 4-chloro-7-(4-{4-[4-(3-{4-[2-(2,6-dioxopiperidin-3-yl)-4methoxy-3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridine-6-yl]piperazine-1yl-phenyl-propyl1-piperildine)piperidine] H-indole-3-carbonitrile; 7-(4-{4- [4-({4- [5-(2,4-dioxo-1-yl)-1 H-indol-1yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-4-fluoro-1H-indole;carbon3-carbon 4-chloro-7-(4-{4-[4-({4-[5-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-1 H-indotrile; 4-chloro-7-[(3 R *)-1-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4methoxy-3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperazin-yl]piperidin-phedin3methyl) -yl]-1 H-indole-3 -carbonitrile; Petition 870250080967, dated 09 / 09 / 2025, p. 100 / 523 / 482 4-chloro-7-[(3 S *)-1-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4methoxy-3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperazin-yl]piperidin-pheridin-methyl) -yl]-1 H-indole-3 -carbonitrile; 4-chloro-7-[(3 R *)-1-{4- [4-({4- [2-(2,6-dioxopiperidin-3 -yl)-1oxo-2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1yl-1-3-phenyl-indoperil] 4-chloro-7-[(3 S *)-1-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1oxo-2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1yl] H-3-3carbonindotripyridine-1-1 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidine-3-yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]piperazine-1-yl}-4-methyl-1-carbonindol3; 4-chloro-7-[(3 R *)-1-{4-[1-({1-[2-(2,6-dioxopiperidin-3-yl)-1oxo-2,3-di-hydro-1 H-isoindol-5-yl]piperidin-4-yl}methyl)piperidin-4yl]H-car-bonindo}piperiladin-3;3 4-chloro-7-[(3 S *)-1-{4-[1-({1 -[2-(2,6-dioxopiperidin-3-yl)-1oxo-2,3-di-hydro-1 H-isoindole-5-yl]piperidin-4-yl}methyl)piperidin-4yl]H-3-carbonyl-ylpyperidine-1-1 4-chloro-7-[(3 R *)-1-{4-[1-({1- [2-(2,6-dioxopiperidin-3 -yl)-4methoxy-3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperidin-4piperidin-pheridin-methyl) -yl]-1 H-indole-3 -carbonitrile; 4-chloro-7-[(3 S *)-1-{4-[1-({1-[2-(2,6-dioxopiperidin-3-yl)-4methoxy-3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperidin-4peridin-pheryln}methyl)piperidine -yl]-1 H-indole-3 -carbonitrile; 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6-fluoro1,3-dioxo-2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}methyl)piperidine-1carbonyl-3-1-}phenyl -carbonytrile; Petition 870250080967, dated 09 / 09 / 2025, p. 101 / 523 / 482 7-[4-(4-{[1-({1-[2-(2-(2,6-dioxopiperidin-3) -yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperidin-4-yl}methyl)piperidin-4-yl]oxy}phenyl)piperidin-carbon1-fluorol]-3-4 4-chloro-7-(4-{4-[4-({4-[5-(2,4-dioxo-1,3-diazinan-1-yl)-7methyl-1 H-indol-1 -yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)1H-indol-3-carbonitrila; 4-chloro-7-(4-{4-[4-({4-[6-(2,4-dioxo-1,3-diazinan-1-yl)-1methyl-1 H-pyrrolo[3,2-b]pyridin-2-yl]piperidin-1-yl}methyl)piperidin-1yl]phenyl}piperidin-1-yl)-1 H-indol-3-carbonitrila; 4-{4-[(1-{4-[(3 S)-1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin3-yl]phenyl}piperidin-4-yl)methyl]piperazin-1-yl}- N-(2,6-dioxopiperidin-3-yl)-2fluorobenzamida; 4-{4-[(1-{4-[1-(3-cyano-4-fluoro-1 H-indol-7-yl)piperidin-4yl]phenyl}piperidin-4-yl)methyl]piperazin-1-yl}- N-(2,6-dioxopiperidin-3-yl)-2fluorobenzamida; 4-{4-[(1-{4-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4yl]phenyl}piperidin-4-yl)methyl]piperazin-1-yl}- N-(2,6-dioxopiperidin-3-yl)-2fluorobenzamida; 7-[4-(4-{[4-({1-[2-(2,6-dioxopiperidin-3 -yl)-1-oxo-2,3-dihydro-1H-isoindol-5-yl]piperidine-4-yl}methyl)piperazine-1yl]methyl}phenyl)piperidin-H-1-carobonyl-1-1-4 4-chloro-7-(4-{ 6-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]pyridin-3-yl}piperidin-1-yl)-1 Carbonitrile-3; 4-chloro-7-(4-{6-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3di-hydro-1 H-isoindol-5-yl]piperazine-1-yl} methyl)piperidin-1-yl]pyridin-3yl bony}piperilane-3-1-1-1-1 Petition 870250080967, dated 09 / 09 / 2025, p. 102 / 523 / 482 4-chloro-7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}piperidin-1-yl)phenyl]piperidin- 1-tribonil};3H-indole 4-chloro-7-[4-(4-{4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol1-yl][1,4'-bipiperidine]-1'-yl}phenyl)piperidin-1-yl]-1 H-indol-3-carbonitrile; 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy1-oxo-2,3-di-hydro-1H-isoindole-5 -yl]piperazine-1-yl}methyl)piperidine-1yl]phenyl}piperidin-1-yl)-1-methyl-1H-indole-3-carbonitrile; 4-chloro-7-(4-{3-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3di-hydro-1 H-isoindol-5-yl]piperazine-1-yl} methyl)piperidin-1-yl]phenyl}piperidin-H1-caryndoyl)-1 4-chloro-7-[(3 X)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-2methyl-1 H-indol-1 -yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidine-1-car-1-yl] 4-chloro-7-[(3 X *)-3-{6-[4-({4-[4-(2,4-dioxo- 1,3-diazinan-1-yl)1H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1-yl]pyridin-3-ylbonyl}piperidine-3-1-H 4-chloro-7-[(3 R *)-3-{6-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)1H-indol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]pyridin-3-yl}piperidin-H-1carbonitril-yl]1 4-chloro-7-[(2 X *)-2-{4-[4-({4-[4-(2,4-dioxo- 1,3-diazinan-1-yl)1H-indole-1-yl]piperidine-1-yl}methyl}piperidin-1-yl]phenyl}morpholin-4-trilyl-;-1H 4-chloro-7-[(2 R *)-2-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)1H-indol-1-yl]piperidine-1-yl}methyl)piperidin-1-yl]phenyl}morpholin-4-yl trinyl-;-3-Hindo 4-chloro-7-[(2 X *)-2-{4-[4-({4-[4-(2,4-dioxo- 1,3-diazinan-1-yl)1H-indol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}morpholin-4-bonitrile-3-3-H Petition 870250080967, dated 09 / 09 / 2025, p. 103 / 523 / 482 4-chloro-7-[(2 R *)-2-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)1H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1-yl]phenyl}morpholin-4-zontrila]-3; 4-chloro-7-[(3 R *)-3-{6-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)1H-indol-1 -yl]piperidin- 1-yl}methyl)piperidine-1-yl]pyridazin-3-carbon}tripyrila-1H-1-H-1 4-chloro-7-[(3 S*)-3-{6-[4-({4-[4-(2,4-dioxo- 1,3-diazinan-1-yl)1H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1-yl]pyridazin-3-yl}piperidin-1-yl]1H-indol-3-carbonitrila; 4-chloro-7-(4-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-2methyl-1H-indol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)1H-indol-3-carbonitrila; 4-chloro-7-(4-{2-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3di-hidro-1 H-isoindol-5-yl]piperazin-1-yl} methyl)piperidin-1-yl]pyrimidin-5 yl}piperidin-1-yl)-1 H-indol-3-carbonitrila; 4-chloro-7-(4-{2-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]pyrimidin-5 -yl}piperidin-1-yl)1H-indol-3-carbonitrila; 7-(4-{4-[(2 R )-2-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-yl]piperazin-1-yl}methyl)morpholin-4-yl]phenyl}piperidin-1yl)-4-fluoro-1H-indol-3-carbonitrila; 4-chloro-7-(4-{4-[(2 R )-2-({4-[2-(2,6-dioxopiperidin-3-yl)-1oxo-2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)morpholin-4yl] H-phenyl}ylpiperiladine-1;3 7-(4-{4-[7-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindol-5-yl]piperazine-1-yl}methyl)-2-yl-azaspiro[3.5]nonan-2-peril-14-flu-phenyl} pi H-indole-3 -carbonitrile; Petition 870250080967, dated 09 / 09 / 2025, p. 104 / 523 / 482 4-chloro-7-(4-{4-[7-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3di-hydro-1 H-isoindol-5-yl]piperazine-1-yl} methyl)-2-azaspiro[3.5]nonanyl-1})piperidin-2yl] H-indole-3-carbonitrile; 4-chloro-7-[(3 5>3-{4-[7-({4-[2-(2,6-dioxopiperidine-3-yl)-1oxo-2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)-2-azaspiro[3.5]nonan2-yl]phenyl}piperidine-1-yl]-1H-indole-3-carbonitrile; 4-chloro-7-[(3 5)-3-{4-[7-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)1H-indol-1-yl]piperidin-1-yl}methyl)-2-azaspiro[3.5]nonan-2-yl]phenyl}piperidin1-carbonitril]-1H 4-chloro-7-[(3 R )-3-{4-[4-({4-[6-(2,4-dioxo- 1,3-diazinan-1-yl)1-methyl-1 H-indol-2-yl]piperidin-1 -yl}methyl}car)piperidin-1-yl]phenyl}indazopiperidine]H3-1 -1 7-[(3 5)-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1-yl]phenyl}piperior-13-inda-fluzotriyl]- 7-[(3 5)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol1-yl]piperidin- 1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1 -yl]-1;4-carbonyl fluoro-3 7-(4-{4-[7-({4- [4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1yl]piperidin-1-yl}methyl)-2-azaspiro[3.5]carbon-2-yl]phenyl}piperidin-1-ibonirol-l-3-4fluf 4-chloro-7-[(3 R )-3-{4-[4-({4-[6-(2,4-dioxo- 1,3-diazinan-1-yl)5-fluoro-1-methyl-1 H-indol-2-yl]piperidin-1-yl}methyl)piperidin-1yl-1]H-3-phenyl-indoperidine] 4-chloro-7-[(3 5)-3-{4-[4-({4-[6-(2,4-dioxo-1,3-diazinan-1-yl)-5fluoro-1 -methyl-1 H-indol-2-yl]piperidine-1 -yl}methyl)piperidin-1]peri-1-phenyl]pi H-indole-3-carbonitrile; Petition 870250080967, dated 09 / 09 / 2025, p. 105 / 523 / 482 4-chloro-7-[(3 R )-3-{4-[4-({4-[6-(2,4-dioxo- 1,3-diazinan-1-yl)5-fluoro-1-methyl-1 H-indol-2-yl]piperidin-1-yl}methyl)piperidin-1yl-3-phenyl-indaryl}pyridine-1; 4-chloro-7-[(3 S)-3-{4-[4-({4-[6-(2,4-dioxo-1,3-diazinan-1-yl)-5fluoro-1 -methyl-1 H-indol-2-yl]piperidin-1 -yl}methyl)piperidin-1 il-peridine]phenyl-yl}pi H-indazole-3-carbonitrile; 7-(4-{4- [4-({4- [6-(2,4-dioxo-1,3-diazinan-1-yl)-1-methyl-1 Hindol-2-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-4-fluoro-4-fluoro-1H-carbonitrile;3H-carbonitrile 7-(4-{4- [4-({4- [4-(2,4-dioxo-1,3-diazinan-1-yl)-2-methyl-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-4-fluoro-;3H-carbonitrile 4-chloro-7-(4-{4-[7-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidine-1-yl}methyl)-2-azaspiro[3.5]carnon-2-yl]phenyl}piperidine-1 H-1yl 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridine-6-yl]piperazine-1yl}methylperi-1]piperidin-1}piperidin-1-1- H-indazole-3-carbonitrile; 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy-3-oxo2,3-di-hydro-1 H-pyrrolo[3,4-c]pyridine-6-yl]piperazine-1-yl}methyl)piperidine-1yl]phenyl}piperidin-1-yl)-4-fluoro-1H-indazol-3-carbonitrile; 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1-carbon]phenyl}p iperidin-1 -indazorol-)-3-4fluflu 4-chloro-7-(4-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-1H-indazol;3-carbonitrile Petition 870250080967, dated 09 / 09 / 2025, p. 106 / 523 / 482 7-(4-{4- [4-({4- [4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-4-fluoro-1Hindazotrila; -3 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-1-yl}-4-carbonizomethyl-3-H 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1yl]phenyl}piperidin-4-indacarzomethryl-1-yl) 7-{(3 S*)-3-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]pyrrolidin-1-yl}-1-carbonindothyl-; 7-{(3 R *)-3-[4-(4-{4-[2-(2,6-dioxopiperidine-3-yl)-1-oxo-2,3-dihydro-1H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]pyrrolidin-1-yl}-Hybonindol-4-methyl- N-[1-(4-chloro-3-cyano-1 H-indazol-7-yl)piperidin-4-yl]-4-[4-({ 4[4-(2,4-dioxo-1,3-diazinan- 1-yl)-1 H-indole-1 -yl]piperidine-1 -gold-yl-perimithyl}methyl]tweezers N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidine-4-yl]-4-[4-({4[5-(2,4-dioxo-1,3-diazinan- 1-yl)-1 H-indol-1 -yl]piperidin-1 -yl-thyl-methyl-methyl-2benzadine N-[1-(4-chloro-3-cyano-1~{H}-indol-7-yl)-4-piperidyl]-4-[4-[4[4-[(2,6-dioxo-3-piperidyl)carbamoyl]-3-fluoro-phenyl]piperazine-1-yl]perimithyl]-1pi-benzene N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-(4-{[6(2,6-dioxopiperidin-3-yl)-5,7-dioxo-3,5,6,7-tetra-hydropyrrole[3,4-f]isoindol2(1H)-yl]methyl}piperidin-miorobenza-2mif-yl-yl) Petition 870250080967, dated 09 / 09 / 2025, p. 107 / 523 / 482 N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4[6-(2,4-dioxo-1,3-diazinan- 1-yl)-5-fluoro-1-methyl-1 H-indol-2-yl]piperidin-1yl}methyl)piperidin-1-yl] -2-fluorobenzamida; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-di-hidro-1 H-benzimidazol-4yl]piperazin-1 -yl}methyl)piperidin-1-yl]-2-fluorobenzamida; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4[6-(2,4-dioxo-1,3-diazinan- 1-yl)-1-methyl-1 H-indol-2-yl]piperidin-1 yl}methyl)piperidin-1-yl] -2-fluorobenzamida; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hidro-1H-isoindol-5-yl]piperazin-1yl}methyl)piperidin-1-yl] -2-fluorobenzamida; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4[4-(2,4-dioxo-1,3-diazinan- 1-yl)-1 H-indol-1 -yl]piperidin-1 -yl}methyl)piperidin1-yl]-2-fluorobenzamida; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4[2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo-2,3-di-hydro-1H-isoindol-5yl]piperidin- -yl}methyl)piperidine-1-yl]-2-fluorobenzamide; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidine-4-yl]-2-cyano-4[4-({4-[4-(2,4-dioxo-1,3-diazinan- 1-yl)-1 H-indol-1 -yl]piperidin-1]piperinyldinenzamidate1) N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidine-4-yl]-4-[4-({4[4-(2,4-dioxo-1,3-diazinan- 1-yl)-1 H-indol-1 -yl]piperidine-1 -yl-methylforo-methylberinza-2pi6-dine N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4[4-(2,4-dioxo-1,3-diazinan- 1-yl)-1 H-indol-1 -yl]piperidin-1 -yl-methyl;}-methylbenzamide]piperidine Petition 870250080967, dated 09 / 09 / 2025, p. 108 / 523 / 482 N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-3-cyano-4[4-({4-[4-(2,4-dioxo-1,3-diazinan- 1-yl)-1 H-indol-1 -yl]piperidin-1]piperinyldinenzamidate1) N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-5-(4-{4-[2(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo-2,3-di-hidro-1 H-isoindol-5yl]piperazin-1 -yl}piperidin-1-yl)pyridine-2-carboxamide; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-5-[4-({4[4-(2,4-dioxo-1,3-diazine-1-yl)-1 H-indol-1 -yl]piperidin-1 -yl}methyl)piperidin1-yl]pyridine-2-carboxamida; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-5-[4-({4[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hidro-1H-isoindol-5-yl]piperazin-1yl}methyl)piperidin-1-yl]pyridine-2 -carboxamide; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-5-[4-({4[2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo-2,3-di-hidro-1H-isoindol-5yl]piperazin-1 -yl}methyl)piperidin-1-yl]pyridine-2-carboxamide; N-[1-(4-chloro-3-cyano-1 H-indazol-7-yl)piperidin-4-yl]-5-[4-({ 4[4-(2,4-dioxo-1,3-diazine- 1-yl)-1 H-indol-1 -yl]piperidin-1 -yl}methyl)piperidin1-yl]pyridine-2-carboxamida; N-[1-(3-cyano-4-methyl-1 H-indol-7-yl)piperidin-4-yl]-5-[4-({4[2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo-2,3-di-hydro-1H-isoindol-5yl] -yl}methyl)piperidine-1-yl]pyridine-2-carboxamide; N-[1-(3-cyano-4-methyl-1 H-indol-7-yl)piperidin-4-yl]-5-[4-({4[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro-1H-isoindol-5-yl]piperamethyl-1-pyridinyl-]piperidine-1yl -carboxamide; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4[4-(2,4-dioxo-1,3-diazinan- 1-yl)-1 H-indol-1 -yl]piperidin-1 -yl}methyl1-methyl;]benzadine Petition 870250080967, dated 09 / 09 / 2025, p. 109 / 523 100 / 482 N-[4-(4-chloro-3-cyano-1 H-indol-7-yl)cyclo-hexyl]-4-[4-({4-[4(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1 -yl]piperidine- 1-yl}methyl}oro)beperinzamide-2fluoride-1 N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4[4-(2,4-dioxo-1,3-diazinan- 1-yl)-1 H-indol-1 -yl]piperidin-1 -yl}methyl)piperidin1-yl]-2,6-difluorobenzamida; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-5-[4-({4[4-(2,4-dioxo-1,3-diazinan- 1-yl)-1 H-indol-1 -yl]piperidin-1 -yl}methyl)piperidin1-yl]pyrazine-2-carboxamide; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-5-[4-({4[4-(2,4-dioxo-1,3-diazinan- 1-yl)-1 H-indol-1 -yl]piperidin-1 -yl}methyl)piperidin1-yl]pyrimidine-2-carboxamide; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4[4-(2,4-dioxo-1,3-diazinan- 1-yl)-1 H-indol-1 -yl]piperidin-1 -yl}methyl)piperidin1-yl]-2-methylbenzamida; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-6-[4-({4[4-(2,4-dioxo-1,3-diazinan- 1-yl)-1 H-indol-1 -yl]piperidin-1 -yl}methyl)piperidin1-yl]pyridazine-3-carboxamide; N-[(3 R *)-1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-3-yl]-5[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro-1 H-isoindol-5yl]piperazine -yl}methyl)piperidine-1-yl]pyridine-2-carboxamide; and N-[(3 S *)-1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-3-yl]-5-[4({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro-1 H-isoindol-5yl]piperazine -yl}methyl)piperidine-1-yl]pyridine-2-carboxamide; or you know pharmaceutically accept two same.

[00502] Compounds specific to the present disclosure include: Petition 870250080967, dated 09 / 09 / 2025, p. 110 / 523 101 / 482 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3di-hydro-1 H-isoindol-5-yl]piperazine-1-yl} methyl)piperidin-1-yl]phenyl}piperidin-H1-caryndoyl)-1 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1-carbon]phenyl}p hyperidin-1 -tril-yl-1-H-3-4flu 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1-carbon]phenyl}p hyperidin-1 -tril-yl-1-H-3-4flu 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1-carbon]phenyl}p hyperidin-1 -tril-yl-1-H-3-4flu 4-chloro-7-(4-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-1H-indole;3carbonitrile 7-(4-{4- [4-({4- [4-(2,4-dioxo-1-yl)-1 H-indol-1yl]piperidin-1-yl}methyl)piperidine-1-yl]phenyl}piperidin-1-yl)-4-fluoro-1H-indole;carbon3-carbon 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy1-oxo-2,3-di-hydro-1 H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1yl] H-3-1-ylcarnindotril-1-1; 7-(4-{4- [4-({4- [4-(2,4-dioxo-1-yl)-1 H-indol-1yl]piperidine-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-4-methyl-1 H-indole;3carbonitrile 4-chloro-7-[(3 S)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)1H-indol-1 -yl]piperidine- 1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-carbonyl tri-la] -1; Petition 870250080967, dated 09 / 09 / 2025, p. 111 / 523 102 / 482 4-chloro-7-[(3 X)-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1oxo-2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1yl]H-phenyl-bonyzopiperilane-1;3 4-chloro-7-[(3 X)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)1H-indole-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl-la];-3-Hycarbonitrile 4-chloro-7-[(3 X)-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)^ oxo-2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1yl]phenyl}ylpiperilane];H-1-1 4-chloro-7-[(3 X)-3-{4-[4-({4-[6-(2,4-dioxo-1,3-diazinan-1-yl)-1methyl-1 H-indol-2-yl]piperidine-1-yl}methyl)pip eridin-1-yl]phenyl}piperidin-13H-indoyl}piperidine]; 4-chloro-7-[(3 X)-3-{4-[4-({4-[6-(2,4-dioxo-1,3-diazinan-1-yl)-1methyl-1H-indol-2-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-H-1carbonitrile-yl]1 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1yl]phenyl}piperidin-H4-icarnitril-1-yl)- 4-chloro-7-[4-(4-{4-[(4-{2-[(3 R *)-2,6-dioxopiperidin-3-yl]-7methoxy-1-oxo-2,3-di-hydro-1 H-isoindole-5-yl}piperazine- 1-yl)methyl]piperidinyl-1-]piperidin-]piperidin} H-indole-3-carbonitrile; 4-chloro-7-[4-(4-{4-[(4-{2-[(3 X *)-2,6-dioxopiperidin-3-yl]-7methoxy-1-oxo-2,3-di-hydro-1 H-isoindole-5-yl}piperazine- 1-yl)methyl]piperidinyl-1-]piperidin-]piperidin} H-indole-3-carbonitrile; 4-chloro-7-[4-(4-{4-[(4-{2-[(3 R *)-2,6-dioxopiperidin-3-yl]-1oxo-2,3-di-hydro-1 H-isoindol-5-yl}piperazin-1-yl)methyl]piperidin-1yl}H-phenyl-1-indotrilpiperidine-1; Petition 870250080967, dated 09 / 09 / 2025, p. 112 / 523 103 / 482 4-chloro-7-[4-(4-{4-[(4-{2-[(3 S *)-2,6-dioxopiperidin-3-yl]-1oxo-2,3-di-hydro-1 H-isoindol-5-yl}piperazine-1-yl)methyl]piperidine-1yl}H-phenyl-1-indotrilpiperidine-1; 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1yl]phenyl} piperidin-13-14-luoro-yl) -carbonytrile; 4-chloro-7-[(3 R )-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1oxo-2,3-di-hydro-1 H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1yl]H-phenyl}ylpiperilane-1;3 7-(4-{4- [4-({1- [2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperidin-4-yl}methyl)piperazine-1-yl]phenyl}piperidin-1-yl-la)-1-4carbonyfluoro- 7-[(3 S)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl]-4-fluoro-fluoro-3-carindole 7-[(3 S)-3-{4-[4-({4-[2-(2,6-dioxopiperidine-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl} methyl)piperidin-1-yl]phenyl}piperidin-fluindoryl]-1-4 4-chloro-7-[(3 R )-3-{4-[4-({4-[4-(2,4-dioxo- 1,3-diazinan-1-yl)1H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-carbon] -1 4-chloro-7-[(3 R )-3-{4-[4-({4-[4-(2,4-dioxo- 1,3-diazinan-1-yl)1H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-caronitrile] -3 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-1-yl}-4carbonyl-la H1; Petition 870250080967, dated 09 / 09 / 2025, p. 113 / 523 104 / 482 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-1-yl}-4-methyl-1H-carbonitrilel; 7-{4-[4-(4-{4-[4-(2,4-dioxo-1,3-diazinan-1 -yl)-1 H-indol-1yl]piperidin-1-yl}butoxy)phenyl]piperidin-1-yl}-4-methyl-1 H-indol-3 -carbonitrile; or you know pharmaceutically accept two same.

[00503] Additional specific compounds from this descriptive report include: 4-chloro-7-(4-{4-[7-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidine-1-yl}methyl)-2-azaspiro[3.5]carnon-2-yl]phenyl}piperidine-1 H-1yl 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridine-6-yl]piperazine-1yl}methylperi-1]piperidin-1}piperidin-1-1- H-indazole-3-carbonitrile; 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy-3-oxo2,3-di-hydro-1 H-pyrrolo[3,4-c]pyridine-6-yl]piperazine-1-yl}methyl)piperidine-1yl]phenyl}piperidin-1-yl)-4-fluoro-1H-indazol-3-carbonitrile; 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1-carbon]phenyl}p iperidin-1 -indazorol-)-3-4fluflu 4-chloro-7-(4-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-1H-indazol;3-carbonitrile 7-(4-{4- [4-({4- [4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-4-fluoro-1Hindazotrila; -3 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-1-yl}-4-carbonizomethyl-3H Petition 870250080967, dated 09 / 09 / 2025, p. 114 / 523 105 / 482 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1yl]phenyl}piperidin-4-indacarzomethryl-1-yl) 7-{(3 X *)-3-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]pyrrolidin-1-yl}-Hybonindol-4-methyl- 7-{(3 R *)-3-[4-(4-{4-[2-(2,6-dioxopiperidine-3-yl)-1-oxo-2,3-dihydro-1H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]pyrrolidin-1-yl}-Hybonindol-4-methyl- N-[1-(4-chloro-3-cyano-1 H-indazol-7-yl)piperidin-4-yl]-4-[4-({ 4[4-(2,4-dioxo-1,3-diazinan- 1-yl)-1 H-indole-1 -yl]piperidine-1 -gold-yl-perimithyl}methyl]tweezers N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4[5-(2,4-dioxo-1,3-diazinan- 1-yl)-1 H-indol-1 -yl]piperidin-1 -yl}methyl)piperidin1-yl]-2-fluorobenzamida; N-[1-(4-chloro-3-cyano-1~{H}-indol-7-yl)-4-piperidyl]-4-[4-[[4[4-[(2,6-dioxo-3-piperidyl)carbamoyl]-3-fluoro-phenyl]piperazin-1-yl]methyl]-1piperidyl]-2-fluoro-benzamida; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-(4-{[6(2,6-dioxopiperidin-3-yl)-5,7-dioxo-3,5,6,7-tetra-hidropyrrolo[3,4-f]isoindol2(1H)-yl]methyl}piperidin-1-yl)-2-fluorobenzamida; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4[6-(2,4-dioxo-1,3-diazinan- 1-yl)-5-fluoro-1-methyl-1 H-indol-2-yl]piperidin-1yl}methyl)piperidin-1-yl] -2-fluorobenzamida; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-di-hidro-1 H-benzimidazol-4yl]piperazin-1 -yl}methyl)piperidin-1-yl]-2-fluorobenzamida; Petition 870250080967, dated 09 / 09 / 2025, p. 115 / 523 106 / 482 N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4[4[6-(2,4-dioxo-1,3-diazinan- 1-yl)-1-methyl-1 H-indol-2-yl]piperidin-1 periminzabe}-2methyl-methyl-pyri] N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidine-4-yl]-4-[4-({4[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro-1 H-isoindol-5-yl]piperamethyl-1-]piperidin-]piperidin-] -2-fluorobenzamide; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4[4-(2,4-dioxo-1,3-diazinan- 1-yl)-1 H-indol-1 -yl]piperidin-1 -yl-thyl-methyl-methyl-2benzadine N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4[2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo-2,3-di-hydro-1 H-isoindol-5yl] -yl}methyl)piperidine-1-yl]-2-fluorobenzamide; and N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidine-4-yl]-2-cyano-4[4-({4-[4-(2,4-dioxo-1,3-diazinan- 1-yl)-1 H-indol-1 -yl]piperidin-1]piperinyldinenzamidate1) or you know pharmaceutically accept two same. Specific compounds I added from this descriptive report include: 4-chloro-7-[(3 R )-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4methoxy-3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperazin-1pherydin-1perinyl}-methyl)piperazine -yl]-1 H-indole-3 -carbonitrile; 7-{4-[4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1,3-dioxo2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]piperidine-1-yl};-4carbonyl-1 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy1,3-dioxo-2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1-peridin-1]phenyl}pi H-indole-3-carbonitrile; Petition 870250080967, dated 09 / 09 / 2025, p. 116 / 523 107 / 482 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]lapiperidine-1-yl};-4carbonitril-1 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6-fluoro1,3-dioxo-2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1-peridin-1]phenyl}pi H-indole-3-carbonitrile; 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1yl]phenyl} piperine-1-4-flu-1-yl -carbonytrile; 4-chloro-7-[(3 5)-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6fluoro-1,3-dioxo-2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}methyl-1-piperil1-pidine]-yl H-indole-3 -carbonitrile; 4-chloro-7-[(3 R )-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6fluoro-1,3-dioxo-2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piphenyl-iperidindol]-1-yl] -carbonytrile; 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxo2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1yl]phenyl}piperidin-1; H-1-yl-indo) 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxo-2,3-dihydro-1 H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-1 -yl}-4-methyl-3-1 Hyndotrile; 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-1-yl}-1 H-indol-3carbonitrile; 7-{4-[4-(4-{4-[4-(2,4-dioxo-1,3-diazinan-1 -yl)-1 H-indol-1yl]piperidin-1-yl}butoxy)phenyl]piperidin-1-yl}-1 H-indol-3-carbonitrile; 7-(4-{4- [4-({4- [4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-1 H-indol-3carbonitrile; Petition 870250080967, dated 09 / 09 / 2025, p. 117 / 523 108 / 482 4-chloro-7-(4-{5-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy1-oxo-2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1yl]piperidine-1-2-yl H-indole-3-carbonitrile; 4-chloro-7-(4-{5-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperazine-1yl}methyl-1-yl}piperidin-2) H-indol- 3-carbonitrile; 4-chloro-7-(4-{5-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]pyridin-2-yl}piperidin-1-yl)-1Hycarbonitrile-3; 4-chloro-7-(4-{ 6-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidine-1-yl}methyl)piperidin-1-yl]pyridazine-3-yl}piperidin-1-yl-la)-1 Hindol 4-chloro-7-(4-{6-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1-yl]pyridazin-3-1-ylbonytripyridine-1; 4-chloro-7-[(3 R *)-3-{5-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)1H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1-yl]pyridin-2-yl}piperil-1-H-1-yl]indo 4-chloro-7-[(3 S*)-3-{5-[4-({4-[4-(2,4-dioxo- 1,3-diazinan-1-yl)1H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1-yl]pyridine-2-ylbonyl}piperidine-3-1-H 4-chloro-7-(4-{5-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidine-1-yl}methyl)piperidin-1-yl]pyrazine-2-yl}piperidin-1-yl-la);-3-Hycarbonitrile 4-chloro-7-(4-{5-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1-yl]pyrazine-2-1-ylbonindotril)pyridin-1; Petition 870250080967, dated 09 / 09 / 2025, p. 118 / 523 109 / 482 7-[4-(4-{4-[(4-{[[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3di-hydro-1 H-benzimidazol-4-yl]methyl}piperazine-1-yl)methyl]piperidine-1yl}phenyl-1methyl-]piperidine H-indole-3-carbonitrile; 4-chloro-7-[4-(4-{4-[(4-{[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2oxo-2,3-di-hidro-1 H-benzimidazol-4-yl]methyl}piperazin-1-yl)methyl]piperidin1-yl}phenyl)piperidin-1 -yl]-1 H-indol-3 -carbonitrila; 7-[4-(4-{4-[(4-{[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3di-hidro-1H-benzimidazol-4-yl]methyl}piperazin-1-yl)methyl]piperidin-1yl}phenyl)piperidin-1-yl] -4-fluoro-1 H-indol-3 -carbonitrila; 4-chloro-7-(4-{4-[4-({4-[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2oxo-2,3-di-hidro-1 H-benzimidazol-4-yl]piperazin-1-yl}methyl)piperidin-1yl]phenyl}piperidin-1-yl)-1 H-indol-3-carbonitrila; 4-chloro-7-[(3 5)-3-(4-{4-[(4-{[1-(2,6-dioxopiperidin-3-yl)-3methyl-2-oxo-2,3-di-hidro-1 H-benzimidazol-4-yl]methyl}piperazin-1yl)methyl]piperidin-1 -yl}phenyl)piperidin- 1-yl]-1 H-indol-3-carbonitrila; 7-[(3 5)-3-(4-{4-[(4-{[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2oxo-2,3-di-hydro-1 H-benzimidazol-4-yl]methyl}piperazine-1-yl)methyl]piperidine1-yl}phenyl)piperidine-1-yl]-4-fluoro-1H-indole-3-carbonitrile; 4-chloro-7-{4-[4-(4-{[6-(2,6-dioxopiperidin-3-yl)-5,7-dioxo3,5,6,7-tetra-hydropyrrole[3,4-f]isoindole-2(1 H)-yl]methyl}piperidin-1yl-phenyl)phenyl-bony}yltriperidine-1 4-chloro-7-{(3 S)-3-[4-(4-{[6-(2,6-dioxopiperidin-3-yl)-5,7dioxo-3,5,6,7-tetra-hydropyrrole[3,4-f]isoindole-2(1 H)-yl]methyl}piperidine-1yl)phenyl]piperidine-1-yl}-1H-indazol-3-carbonitrile; and 4-chloro-7-{(3 S)-3-[4-(4-{[6-(2,6-dioxopiperidin-3-yl)-5,7dioxo-3,5,6,7-tetra-hydropyrrole[3,4-f]isoindole-2(1 H)-yl]methyl}piperidine-1yl)phenyl]piperidine-1-yl}-1H-indole-3-carbonitrile; or you know pharmaceutically accept two same. Petition 870250080967, dated 09 / 09 / 2025, p. 119 / 523 110 / 482

[00504] In one embodiment, this descriptive report refers to a compound that is 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3dihydro-1H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin 1-yl)-1 H-indole-3-carbonitrile or a pharmaceutically acceptable salt thereof.

[00505] In one embodiment, this specification relates to a compound that is 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-yl]piperazin-1-yl} methyl)piperidin-1-yl]phenyl}piperidin-1 il)-4-fluoro-1 H-indole-3-carbonitrile or a pharmaceutically acceptable salt thereof.

[00506] In one embodiment, this descriptive report refers to a compound that is 7-(4-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1H-indol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-4-fluoro-1H-indol 3-carbonitrile or a pharmaceutically acceptable salt thereof. Petition 870250080967, dated 09 / 09 / 2025, p. 120 / 523 111 / 482

[00507] In one embodiment, this specification refers to a compound that is 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1yl]phenyl}piperidin-1-yl)-1 H-indol-3-carbonitrile or a pharmaceutically acceptable salt thereof.

[00508] In one embodiment, this descriptive report refers to a compound that is 7-(4-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1H-indol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-4-methyl-1H-indol-3carbonitrile or a pharmaceutically acceptable salt thereof.

[00509] In another embodiment, this descriptive report refers to a compound that is 4-chloro-7-[(3-)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazman-1-yl)-1H-indol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl]-1Hindazol-3-carbonitrile or a pharmaceutically acceptable salt thereof. Petition 870250080967, dated 09 / 09 / 2025, p. 121 / 523 112 / 482

[00510] In another embodiment, this descriptive report refers to a compound that is 4-chloro-7-[(3S)-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1oxo-2,3-dihydro-1H-isoindol-5-yl]piperazm-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl]-1H-indazol-3-carbonitrile or a pharmaceutically acceptable salt thereof.

[00511] In another embodiment, this descriptive report refers to a compound that is 4-chloro-7-[(3 5,)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1H-indol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl]-1-Hindol-3-carbonitrile or a pharmaceutically acceptable salt thereof.

[00512] In another embodiment, this descriptive report refers to a compound that is 4-chloro-7-[(3 5)-3-{4-[4-({4[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-yl]piperazin-1yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl]-1H-indol-3-carbonitrile Petition 870250080967, dated 09 / 09 / 2025, p. 122 / 523 113 / 482 or a pharmaceutically acceptable salt thereof.

[00513] In another embodiment, this descriptive report refers to a compound that is 4-chloro-7-[(3S)-3-{4-[4-({4-[6-(2,4-dioxo-1,3-diazman-1yl)-1-methyl-1H-indol-2-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl]-1H-indol-3-carbonitrile or a pharmaceutically acceptable salt thereof.

[00514] In another embodiment, this descriptive report refers to a compound that is 4-chloro-7-[(3S)-3-{4-[4-({4-[6-(2,4-dioxo-1,3-diazman-1yl)-1-methyl-1H-indol-2-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl]-1H-indazol-3-carbonitrile or a pharmaceutically acceptable salt thereof.

[00515] In another embodiment, this descriptive report refers to a compound that is 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-Petition 870250080967, dated 09 / 09 / 2025, page 123 / 523 114 / 482 oxo-2,3-dihydro-1H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1yl]phenyl}piperidin-1-yl)-4-methyl-1 H-indol-3-carbonitrile or a pharmaceutically acceptable salt thereof.

[00516] In another embodiment, this descriptive report refers to a compound that is 7-[(3S)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazman-1-yl)-1-Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl]-4-fluoro-1H-indol-3-carbonitrile or a pharmaceutically acceptable salt thereof.

[00517] In another embodiment, this descriptive report refers to a compound that is 7-{4-[4-(4-{4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1H-indol-1-yl]piperidin-1-yl}butoxy)phenyl]piperidin-1-yl}-4-fluoro-1H-indol-3carbonitrile or a pharmaceutically acceptable salt thereof.

[00518] In another embodiment, this descriptive report refers to a compound that is 4-chloro-7-[(3S)-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4 Petition 870250080967, dated 09 / 09 / 2025, p. 124 / 523 115 / 482 methoxy-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-yl]piperazin-1yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl]-1H-indol-3-carbonitrile or a pharmaceutically acceptable salt thereof.

[00519] In another embodiment, this specification refers to a compound that is 4-chloro-7-[(3 S)-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6fluoro-1,3-dioxo-2,3-dihydro-1 H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin1-yl]phenyl}piperidin-1-yl]-1 H-indol-3-carbonitrile or a pharmaceutically acceptable salt thereof.

[00520] In another embodiment, this descriptive report refers to a compound that is 4-chloro-7-[(3 5,)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-2-methyl-1H-indol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl]-1H-indol-3-carbonitrile Petition 870250080967, dated 09 / 09 / 2025, p. 125 / 523 116 / 482 or a pharmaceutically acceptable salt thereof.

[00521] An additional embodiment provides any of the embodiments, claims or aspects defined herein on the condition that one or more specific Examples (for example, one Example, or two or three specific Examples) selected from the group consisting of Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 153, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180 and 181 should be individually excluded.

[00522] The compounds of formula (I) and the PROTAC compounds containing linking units of formula (Ia) may have one or more chiral centers and it will be recognized that these compounds may be prepared, isolated and / or supplied with or without the presence of one or more of the other possible enantiomeric and / or diastereomeric isomers of said compounds or that these isomers may be supplied in any relative proportions. Petition 870250080967, dated 09 / 09 / 2025, page 126 / 523 117 / 482 The preparation of enantioenriched / enantiopure and / or diastereoenriched / diastereopure compounds can be carried out by standard organic chemistry techniques that are well known in the art, for example, by synthesis from enantioenriched or enantiopure starting materials and / or by using a suitably enantioenriched or enantiopure catalyst during synthesis and / or by resolving a racemic or partially enriched mixture of stereoisomers, for example, by chiral chromatography.

[00523] Consequently, in one embodiment, a composition is provided comprising a compound of formula (I) [or PROTAC compound containing a unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, optionally in conjunction with one or more of the other stereoisomeric forms of the compound of formula (I) [or PROTAC compound containing a unit of formula (Ia)] or pharmaceutically acceptable salt thereof, wherein the compound of formula (I) [or PROTAC compound containing a unit of formula (Ia)] or pharmaceutically acceptable salt thereof is present in the composition with a diastereomeric excess (% of - diastereomeric excess) of > 90 %.

[00524] In another modality, the % in the aforementioned composition is > 95%.

[00525] In another modality, the % in the aforementioned composition is > 98%.

[00526] In another modality, the % in the aforementioned composition is > 99%.

[00527] In another embodiment, a composition is provided comprising a compound of formula (I) [or PROTAC compound containing a unit of formula (Ia), as defined herein] or a pharmaceutically acceptable salt thereof, optionally in conjunction with one or more of the other stereoisomeric forms of the compound of formula (I) [or Petition 870250080967, dated 09 / 09 / 2025, page 127 / 523 118 / 482 compound PROTAC containing one unit of formula (Ia), as defined herein] or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) [or compound PROTAC containing one unit of formula (Ia), as defined herein] or a pharmaceutically acceptable salt thereof is present in the composition with an enantiomeric excess (%ee) of > 90 %.

[00528] In another modality, %ee in the aforementioned composition is > 95%.

[00529] In another modality, %ee in the aforementioned composition is > 98%.

[00530] In another modality, %ee in the aforementioned composition is > 99%.

[00531] In another embodiment, a composition is provided comprising a compound of formula (I) [or PROTAC compound containing a unit of formula (Ia), as defined herein] or a pharmaceutically acceptable salt thereof, optionally in conjunction with one or more of the other stereoisomeric forms of the compound of formula (I) [or PROTAC compound containing a unit of formula (Ia), as defined herein] or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) [or PROTAC compound containing a unit of formula (Ia), as defined herein] or a pharmaceutically acceptable salt thereof is present in the composition with an enantiomeric excess (%ee) of > 90% and a diastereomeric excess (%de) of > 90%.

[00532] In other forms of the composition mentioned above, %ee and %de can assume any combination of values ​​as mentioned below: • %ee is < 5% and %de is > 80%. • %ee is < 5% and %de is > 90%. • %ee is < 5% and %de is > 95%. Petition 870250080967, dated 09 / 09 / 2025, page 128 / 523 119 / 482 • %ee is < 5% and %de is > 98%. • %ee is > 95% and %de is > 95%. • %ee is > 98% and %de is > 98%. • %ee is > 99% and %de is > 99%.

[00533] In another embodiment, a pharmaceutical composition is provided comprising a compound of formula (I) [or PROTAC compound containing a unit of formula (Ia), as defined herein], or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable excipient.

[00534] In one embodiment, a pharmaceutical composition is provided comprising a compound of formula (I) [or PROTAC compound containing a unit of formula (Ia), as defined herein], or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable excipient, optionally further comprising one or more of the other stereoisomeric forms of the compound of formula (I) [or PROTAC compound containing a unit of formula (Ia), as defined herein], or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) [or PROTAC compound containing a unit of formula (Ia), as defined herein], or a pharmaceutically acceptable salt thereof is present in the composition with an enantiomeric excess (%ee) of > 90 %.

[00535] In another modality, the %ee in the aforementioned composition is > 95 %.

[00536] In another modality, the %ee in the aforementioned composition is > 98 %.

[00537] In another modality, the %ee in the aforementioned composition is > 99%.

[00538] In one embodiment, a pharmaceutical composition is provided comprising a compound of formula (I) [or compound PROTAC Petition 870250080967, dated 09 / 09 / 2025, page 129 / 523 120 / 482 containing one unit of formula (Ia), as defined herein], or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable excipient, optionally further comprising one or more of the other stereoisomeric forms of the compound of formula (I) [or PROTAC compound containing one unit of formula (Ia), as defined herein], or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) [or PROTAC compound containing one unit of formula (Ia), as defined herein], or a pharmaceutically acceptable salt thereof is present in the composition with a diastereomeric excess (% of) of > 90 .

[00539] In another modality, the % of the composition mentioned above is > 95%.

[00540] In another modality, the % of the composition mentioned above is > 98%.

[00541] In another modality, the % in the aforementioned composition is > 99%.

[00542] In one embodiment, a pharmaceutical composition is provided comprising a compound of formula (I) [or PROTAC compound containing a unit of formula (Ia), as defined herein], or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable excipient, optionally further comprising one or more of the other stereoisomeric forms of the compound of formula (I) [or PROTAC compound containing a unit of formula (Ia), as defined herein], or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) [or PROTAC compound containing a unit of formula (Ia), as defined herein], or a pharmaceutically acceptable salt thereof is present in the composition with an enantiomeric excess (%ee) of > 90% and a diastereomeric excess (%de) of > 90%. Petition 870250080967, dated 09 / 09 / 2025, page 130 / 523 121 / 482

[00543] In other embodiments of the aforementioned pharmaceutical composition, %ee and %de may assume any combination of values ​​as mentioned below: • %ee is > 95% and %de is > 95%. • %ee is > 98% and %de is > 98%. • %ee is > 99% and %de is > 99%.

[00544] The compounds of formula (I) [or PROTAC compound containing a unit of formula (Ia), as defined herein], and pharmaceutically acceptable salts thereof may be prepared, used or supplied in amorphous form, crystalline form or semicrystalline form and any given compound of formula (I) [or PROTAC compound containing a unit of formula (Ia), as defined herein], or pharmaceutically acceptable salt thereof may be capable of being formed in more than one crystalline / polymorphic form, including hydrated forms (e.g., a hemihydrate, a monohydrate, a dihydrate, a trihydrate or other hydrate stoichiometry) and / or solvated forms. It should be understood that this descriptive report covers any and all solid forms of the compound of formula (I) [or PROTAC compound containing a unit of formula (Ia), as defined herein], and pharmaceutically acceptable salts thereof.

[00545] In other embodiments, a compound of formula (I) [or PROTAC compound containing one unit of formula (Ia), as defined herein] is provided which can be obtained by the methods described in the 'Examples' section below. Intermediate compounds

[00546] As demonstrated in the experimental section below, compounds of formula (I) or PROTACs of formula (Ia) can be prepared, for example, by the following methods. Petition 870250080967, dated 09 / 09 / 2025, p. 131 / 523 122 / 482

[00547] A compound of formula (I) [or a salt thereof] or a PROTAC compound of formula (Ia) [or a salt thereof] can be prepared from a compound of formula (II): (II) or a salt thereof, where: QA is -G-QH- or -G-(C1-5alkylene)-; G is a direct linkage, -CH2-, -C(=O)-, -O- or -N(RG)-, where R is H or C1-3 alkyl; QH is a saturated or partially unsaturated heterocyclic group containing nitrogen with 4 to 12 members; QD is a direct linkage or C1-2 alkylene optionally replaced by one or more F; RL1 and RL2 together form =O, RL3 is H; where QD is a direct bond and QA is -G-QH-, the value of QH is selected so that QD connects to a C atom of QH; and R1, p, X1, Rn, n, m, R2a, R2b, Q1, Q2, Q3, Q4, Y1, Y2, Y3, Y4, Y5, R3, and q can assume any of the values ​​revealed here for each of these groups / variables, respectively.

[00548] In one embodiment, QH is a saturated heterocyclic group containing nitrogen with 4 to 12 members.

[00549] Consequently, this compound of formula (II), as described above, is an aldehyde that can react with a suitable molecule containing an amine group (for example, a secondary amine group) to form the compound of formula (I) or the PROTAC compound of formula (Ia). Petition 870250080967, dated 09 / 09 / 2025, page 132 / 523 123 / 482 directly or after one or more additional reaction steps. This reaction of said aldehyde with said amine can be carried out under reductive amination conditions, using, for example, NaBH(OAc)3 or another reductive amination protocol known to those skilled in the art.

[00550] This aldehyde can, in turn, be prepared from the corresponding acetal, for example, a compound of formula (II), or a salt thereof, as defined above, except that: RL1 and RL2 are each independently C-1-6 alkoxy (for example, C1-3 alkoxy) or RL1 and RL2 together form -O-(CH2)kO-, wherein k is 2 or 3. This acetal can be converted into the corresponding aldehyde under acidic conditions, for example, using formic acid under conditions well known to those skilled in the art.

[00551] Alternatively, as shown in the following experimental section, the aforementioned aldehyde can be prepared by oxidation of the corresponding primary alcohol, i.e., a compound of formula (II), or a salt thereof, as defined above, except that RL1 is OH and RL2 is H. This oxidation can be carried out using mild oxidizing conditions, for example, Dess-Martin periodinane or some other mild oxidation protocol known to those skilled in the art.

[00552] As shown in the following experimental section, a compound of formula (I) [or a salt thereof] or a PROTAC compound of formula (Ia) [or a salt thereof] can be prepared from a compound of formula (II) or a salt thereof, as described above, except that RL1 is a leaving group and RL2 is H. Consequently, this compound of formula (II) is an electrophile that can react with a molecule containing an amine group (e.g., a secondary amine group) via an alkylation reaction to form the compound of formula (I) or the PROTAC compound of formula (Ia) – directly, or after one or more additional reaction steps. Suitable leaving groups for alkylation reactions are well known to those skilled in the art and include Cl, Br, I, Petition 870250080967, dated 09 / 09 / 2025, page 133 / 523 124 / 482 trifluoromethanesulfonate, mesylate and tosylate. The alkylation reaction conditions are well known to those skilled in the art and generally involve a non-nucleophilic base (e.g., DIPEA) and a polar aprotic solvent (e.g., MeCN). As demonstrated in the following experimental section, in cases where the leaving group is not I, a metal iodide salt can be used in the reaction mixture to form the corresponding iodide in situ (i.e., where RL1 is I) to facilitate the overall alkylation process. As shown in the following experimental section, a compound of formula (II) where RL1 is a bromine leaving group can be prepared from the corresponding primary alcohol (i.e., as already described above, where RL1 is OH and RL2 and RL3 are both H).

[00553] In turn, the above-mentioned primary alcohol compound of formula (II) can be prepared by reducing the corresponding ester compound, i.e., a compound of formula (II), or a salt thereof, as defined above, except that: RL1 and RL2 together form '-O and RL3 is C1-6 alkoxy (e.g., C1-3 alkoxy). This reduction can be carried out using strong reducing conditions, for example, using DIBAL or other stronger reducing conditions that are well known to those skilled in the art.

[00554] Alternatively, as demonstrated in the following experimental section, it may be convenient to form the above-mentioned primary alcohol compound of formula (II) by deprotection of a protected form of the alcohol. For example, deprotection of a compound in which the alcohol is protected by a silicon-based protecting group, using a fluorine source to achieve deprotection, for example, TBAF or other deprotection methods well known to those skilled in the art.

[00555] Therefore, as described above, several compounds of formula (II) and salts thereof may be useful as intermediates in the synthesis of compounds of formula (I) or PROTAC compounds of formula (Ia) and, Petition 870250080967, dated 09 / 09 / 2025, page 134 / 523 125 / 482 Consequently, these intermediate compounds provide an additional aspect of the descriptive report.

[00556] Therefore, in a further aspect, a compound of formula (II) is provided, as shown above, or a salt thereof, wherein: QA is -G-QH- or -G-(C1-5alkylene)-; G is a direct linkage, -CH2-, -C(=O)-, -O- or -N(RG)-, where R is H or C1-3 alkyl; QH is a saturated or partially unsaturated heterocyclic group containing nitrogen with 4 to 12 members; QD is a direct linkage or C1-2 alkylene optionally substituted by one or more F (e.g., 1 or 2 F); and (i) RL1 and RL2 together form '-O and RL3 is H or C1.6 alkoxy (e.g., OMe); (ii) RL1 and RL2 are each independently C1-6 alkoxy (e.g., OMe), and RL3 is H; (iii) RL1 and RL2 together form -O-(CH2)kO-, where k is 2 or 3, and RL3 is H; or (iv) RL1 is OH, OPG1 (where PG1 is a protecting group) or LG1 (where LG1 is a leaving group) and RL2 and RL3 are both H; where QD is a direct bond and QA is -G-QH-, the value of QH is selected so that QD connects to a C atom of QH; and R1, p, X1, X2, X3, X4, n, m, Q, R2a, R2b, Y1, Y2, Y3, Y4, R3 and q can assume any of the values ​​revealed here for each of these groups / variables, respectively.

[00557] In one embodiment, QH is a saturated heterocyclic group containing nitrogen with 4 to 12 members.

[00558] A person skilled in the art is aware of suitable protecting groups for alcohol groups and is therefore aware of suitable PG1 values. For example, PG1 is an alcohol protecting group. Petition 870250080967, dated 09 / 09 / 2025, page 135 / 523 126 / 482

[00559] In one embodiment, PG1 is a silicon-based alcohol protecting group.

[00560] In one embodiment, PG1 is Si(RSl)3, where each RSl independently has a C1-6 hydrocarbyl group.

[00561] In one embodiment, PG1 is tert-butyldimethylsilyl or tert-butyldiphenylsilyl.

[00562] In one embodiment, LG1 is selected from Cl, Br, I, trifluoromethanesulfonate and C1-7 hydrocarbylsulfonate (e.g., mesylate or p-toluenesulfonate).

[00563] In one form, LG1 is Br or I.

[00564] In one modality, LG1 is Br.

[00565] In one embodiment, LG1 is Cl.

[00566] In one form, LG1 is I.

[00567] In one embodiment, LG1 is trifluoromethanesulfonate.

[00568] In one embodiment, LG1 is C1-7 hydrocarbilsulfonate.

[00569] In one form, LG1 is mesylate.

[00570] In one embodiment, LG1 is p-toluenesulfonate.

[00571] In one embodiment, QD is a direct link, -CH2-, -CH2CH2 or -CF2CH2-.

[00572] In one modality, QDé is a direct connection.

[00573] In one modality, QDé CH2.

[00574] In one embodiment, QDé C1-2alkylene optionally replaced by 1 or 2 F.

[00575] In one embodiment, QDé C1-2alkylene.

[00576] In one form, QDé -CH2CH2-.

[00577] In a QDé -CF2CH2- modality.

[00578] In other forms of this descriptive report, formula (II) may be formula (Ila): Petition 870250080967, dated 09 / 09 / 2025, p. 136 / 523 127 / 482 (Ha) where Lx can be any of the groups (1) to (43) mentioned above in conjunction with formula (Ia); and where QA, QD, RL1, rl2 and pin pOjemas assume any of the values ​​revealed here for each of said groups, respectively.

[00579] As demonstrated in the following experimental section, certain compounds of formula (I) and certain PROTACS of formula (Ia) and certain intermediate compounds of formula (II) can be prepared using a compound of formula (iii): (III) or a salt thereof, wherein Gx is OH, in which the oxygen atom of said OH is alkylated by a suitable molecule to form certain compounds of formula (I) or PROTACs of formula (Ia) – directly or after one or more additional reaction steps (for example, via formula (II) as described further below). These alkylation reactions can be carried out under conditions well known to those skilled in the art, for example, using a primary alkyl bromide (or using some other leaving group in place of Br) using a non-nucleophilic base, such as a metal carbonate (for example, K2CO3) in a polar aprotic solvent, such as MeCN, optionally in the presence of a metal iodide salt, such as KI. Petition 870250080967, dated 09 / 09 / 2025, page 137 / 523 128 / 482

[00580] Alternatively, as shown in the following experimental section, a compound of formula (III), wherein GX is -NH(RG) [wherein RG is H or C1-3 alkyl (e.g., Me)] can be used as an intermediate to prepare compounds of formula (I) or PROTACs of formula (Ia) via reductive amination chemistry with a suitable aldehyde-containing compound.

[00581] Alternatively, as shown in the following experimental section, a compound of formula (III), wherein GX is bromine, can be coupled to a secondary amine compound to yield certain compounds of formula (I) or PROTACs of formula (Ia) – directly or after one or more additional reaction steps (e.g., via formula (II), as described above). Similarly, compounds of formula (III), wherein GX is chlorine or trifluoromethanesulfonate, can also be used in a coupling reaction with the relevant secondary amine to yield certain compounds of formula (I) or PROTACs of formula (Ia).This coupling can be performed under palladium-based coupling conditions (e.g., using 'Ruphos Pd G3' and 'Ruphos') in the presence of a base and an anhydrous solvent, such as 1,4-dioxane under an inert atmosphere, or by heating with CuI in the presence of a base, such as K3PO4 in a polar solvent, such as DMSO. Alternatively, as also shown here in the experimental section, a compound of formula (iii), where GX is bromine, can be coupled to a suitable alcohol to form certain compounds of formula (I) or PROTACs of formula (Ia) – directly or after one or more additional reaction steps (e.g., via formula (II), as described further below). This coupling can be performed using a palladium-based reagent such as 'Rockphos Pd G3' in the presence of a base such as Cs2CO3 in a solvent such as toluene.

[00582] Consequently, compounds of formula (iii) and salts thereof may be useful as intermediates in the synthesis of certain compounds of formula (I) or PROTAC compounds of formula (Ia) or compounds of Petition 870250080967, dated 09 / 09 / 2025, page 138 / 523 129 / 482 formula (II) and, consequently, these intermediate compounds provide an additional aspect of the descriptive report.

[00583] Therefore, in a further aspect, a compound of formula (III) is provided, as shown above, or a salt thereof, wherein: GXe OH, Cl, Br, trifluoromethanesulfonate or -NH(RG), wherein Rg is H or C1-3 alkyl; and R1, p, X1, Rn, n, m, R2a, R2b, Q1, Q2, Q3, Q4, Y1, Y2, Y3, Y4, Y5, R3 and q can assume any of the values ​​revealed here for each of these groups / variables, respectively.

[00584] GXe OH, Cl, Br, trifluoromethanesulfonate or -NH(RG), wherein Rg is C1-3 alkyl (e.g., Me).

[00585] In one embodiment, GX is OH, Br, trifluoromethanesulfonate or -NH(Rg), wherein RG is C1-3 alkyl (e.g., Me).

[00586] In one embodiment, GX is OH, Br or -NH(RG), wherein RG is C1-3 alkyl (e.g., Me).

[00587] In one modality, GXé OH or Br.

[00588] In one modality, GXé OH.

[00589] In one modality, GXé Br.

[00590] In one modality, GXé Cl.

[00591] In one embodiment, GX is trifluoromethanesulfonate.

[00592] In one embodiment, GXé -NH(RG), wherein RGé H or Ci3alkyl.

[00593] In one embodiment, GXé -NH(RG), wherein RGé Ci-3alkyl.

[00594] In one form, GXé -NH(Me).

[00595] In additional embodiments of this descriptive report, formula (III) may be LX—GX, wherein LX may be any of the groups (1) to (43) mentioned above in conjunction with formula (Ia); and wherein GX may assume any value(s) disclosed herein for GX. Petition 870250080967, dated 09 / 09 / 2025, page 139 / 523 130 / 482

[00596] As demonstrated in the following experimental section, certain compounds of formula (I) and PROTACs of formula (Ia) can be prepared using an intermediate compound of formula (IV): (IV) or a salt thereof, as further defined below. For example, a compound of formula (IV), or a salt thereof, wherein J is H (i.e., a secondary amine compound) may be coupled to an additional chemical fragment, using chemistry well known to those skilled in the art and exemplified in the following experimental section, to provide a compound of formula (I) or a PROTAC of formula (Ia), directly or after one or more additional reaction steps.

[00597] In turn, this compound of formula (IV), wherein J is H, can be conveniently prepared by deprotection of an N-protected form of the previously mentioned amine compound. Consequently, compounds of formula (IV), wherein J is H, can be conveniently prepared using a compound of formula (IV), wherein J is PG2, wherein PG2 is a nitrogen protecting group (e.g., a C1-6 alkoxycarbonyl group, such as tert-butoxycarbonyl). Therefore, compounds of formula (IV), wherein J is PG2, are useful intermediates in the preparation of compound of formula (I) and PROTAC of formula (Ia) and provide an additional aspect of the descriptive report.

[00598] Therefore, in a further aspect of the descriptive report, a compound of formula (IV) as represented above, or a salt thereof, is provided, wherein: Petition 870250080967, dated 09 / 09 / 2025, p. 140 / 523 131 / 482 J is H or PG2, where PG2 is a nitrogen protecting group (e.g., a tert-butoxycarbonyl group); QA is -G-QH- or -G-(C1-5alkylene)-; G is a direct linkage, -CH2-, -C(=O)-, -O- or -N(RG)-, where R is H or C1-3 alkyl; QB is a direct linkage, -QB1-QB2-QB3- or C1-3 alkylene optionally substituted by one or more F (e.g., 1 or 2); wherein: QB1 and QB3 each independently represent a direct or C1-2 alkylene bond; QB2 is QH, -O-CH2CH2-O-, -O- or -N(RJ)-, where RJ is H or C1-3 alkyl; and each QH (including the J-linked QH ring) is independently a saturated or partially unsaturated heterocyclic group containing nitrogen with 4 to 12 members; wherein the values ​​of Ring QA, QB and QH are selected so that formula (IV) does not contain any NN or NO bonds; and where R1, p, X1, RN, n, m, R2a, R2b, Q1, Q2, Q3, Q4, Y1, Y2, Y3, Y4, Y5, R3 and q can assume any of the values ​​defined here for each of these groups / variables, respectively.

[00599] In one embodiment, each QH (including the “J-linked QH ring”) is independently a saturated heterocyclic group containing nitrogen with 4 to 12 members.

[00600] In one embodiment, the QHé ring is piperidin-1,4-di-yl or piperazin-1,4-di-yl.

[00601] In one modality, J is H.

[00602] In one form, J is PG2.

[00603] In one embodiment, PG2 is C1-6 alkoxycarbonyl.

[00604] In one embodiment, PG2 is tert-butoxycarbonyl. Petition 870250080967, dated 09 / 09 / 2025, p. 141 / 523 132 / 482

[00605] In an embodiment where PG2 is C1-6 alkoxycarbonyl (e.g., tert-butoxycarbonyl), the element 'and salts thereof' in the claim is omitted.

[00606] In additional embodiments, the compound of formula (IV) may assume any combination of alternative values ​​mentioned in relation to QA, QB and QH in any other context, embodiment, aspect or claim found herein.

[00607] In other embodiments of this descriptive report, formula (IV) may be formula (IVa):_______________________ (IVa) wherein LX may be any of the groups (1) to (43) mentioned above in conjunction with formula (Ia); and where QA, QB, QHe J may assume any of the values ​​disclosed herein for each of said groups, respectively.

[00608] As demonstrated in the following experimental section, certain compounds of formula (I) and PROTACs of formula (Ia) can be prepared using an intermediate compound of formula (V): (V) or a salt thereof, provided that: XX is N replaced by J, where J is H; G is a direct linkage, -CH2-, -C(=O)-, -O- or -N(RG)-, where R is H or C1-3 alkyl; Petition 870250080967, dated 09 / 09 / 2025, page 142 / 523 133 / 482 The QH ring is a saturated or partially unsaturated heterocyclic group containing nitrogen with 4 to 12 members; wherein the values ​​of G and the QH ring are selected so that formula (V) does not contain any NN or NO bonds; and where R1, p, X1, RN, n, m, R2a, R2b, Q1, Q2, Q3, Q4, Y1, Y2, Y3, Y4, Y5, R3 and q can assume any of the values ​​defined here for each of these groups / variables, respectively.

[00609] This compound of formula (V) can be converted into a compound of formula (I) or a PROTAC of formula (Ia) by reductive amination or alkylation or other coupling chemistry known to those skilled in the art – to provide the compound of formula (I) or the PROTAC of formula (Ia) directly, or after one or more additional steps.

[00610] In turn, as shown in the following experimental section, this compound of formula (V), or a salt thereof, can be conveniently prepared by deprotection of the corresponding N-protected compound. This N-protected form can be a Boc-protected form (i.e., tert-butoxycarbonyl) or can use another N-protecting group known to those skilled in the art. Consequently, these N-protected compounds are also useful intermediates in the preparation of the compounds of formula (I) and PROTACs of formula (Ia) and provide an additional aspect of the descriptive report.

[00611] Consequently, one aspect of the descriptive report provides a compound of formula (V), or a salt thereof, as described above, except that XX is N replaced by J, where J is PG3 and PG3 is a protecting group. In one embodiment, PG3 is C1-6 alkoxycarbonyl. In one embodiment, PG3 is tert-butoxycarbonyl. In an embodiment where PG3 is C1-6 alkoxycarbonyl (e.g., tert-butoxycarbonyl), the element 'and salts thereof' of the claim is omitted. Petition 870250080967, dated 09 / 09 / 2025, p. 143 / 523 134 / 482

[00612] Other compounds of formula (I) and PROTACs of formula (Ia) - and salts thereof - can be prepared from an intermediate compound of formula (V), or a salt thereof, as described above, except that XX is C=O. This intermediate can be converted into a compound of formula (I) or a PROTAC of formula (Ia) by reductive amination chemistry using a suitable amine-containing compound, using reductive amination conditions that are well known to those skilled in the art, either directly or through one or more additional synthetic steps.

[00613] In turn, as demonstrated in the experimental section below, these compounds of formula (V), wherein XX is C=O, can be conveniently prepared from the corresponding compound wherein the ketone is protected / masked as a ketal. Consequently, these ketal compounds and salts thereof are useful intermediates in the preparation of a compound of formula (I) or a PROTAC of formula (Ia) and provide an additional aspect of the descriptive report.

[00614] Consequently, this ketal compound can be represented as a compound of formula (V), or a salt thereof, as described above, except that XX is C replaced by RU1 and RU2; where RU1 and RU2 are each C1-6 alkoxy; or RU1 and RU2 together represent O-(CH2)uO-, where u is 2 or 3.

[00615] Therefore, in a further aspect of the descriptive report, a compound of formula (V) as represented above, or a salt thereof, is provided, wherein: XX is selected from among: (i) N replaced by J, where J is H or PG3, where PG3 is a protecting group; and (ii) C replaced by oxo, or by RU1 and RU2; where RU1 and RU2 are each C1-6 alkoxy; or RU1 and RU2 together represent -O-(CH2)uO-, where u is 2 or 3; Petition 870250080967, dated 09 / 09 / 2025, p. 144 / 523 135 / 482 G is a direct linkage, -CH2-, -C(=O)-, -O- or -N(RG)-, where R is H or C1-3 alkyl; The QH ring is a saturated or partially unsaturated heterocyclic group containing nitrogen with 4 to 12 members; and the values ​​of G and the QH ring are selected so that formula (V) does not contain any NN or NO bonds; and where R1, p, X1, RN, n, m, R2a, R2b, Q1, Q2, Q3, Q4, Y1, Y2, Y3, Y4, Y5, R3 and q can assume any of the values ​​defined here for each of these groups / variables, respectively.

[00616] In one form, J is H.

[00617] In one form, J is PG3.

[00618] In one embodiment, PG3 is C1-6 alkoxycarbonyl.

[00619] In one embodiment, PG3 is tert-butoxycarbonyl.

[00620] In one embodiment, XX is C=O.

[00621] In one embodiment, XX is replaced by RU1 and RU2; where RU1 and RU2 are each C1-6 alkoxy.

[00622] In one embodiment, XX is replaced by RU1 and RU2; where RU1 and RU2 together represent -O-(CH2)uO-, where u is 2 or 3 (for example, u = 2).

[00623] In one form, G is a direct link or -O-.

[00624] In one embodiment, the QH ring is a saturated heterocyclic group containing nitrogen with 4 to 12 members.

[00625] The values ​​of the QH ring can assume any of the values ​​mentioned here for QH.

[00626] In one embodiment, the QH ring is a piperidine ring, a piperazine ring, a 9-azaspir[5.5]undecane ring or a 3,9-diazaspir[5.5]undecane ring.

[00627] In other forms of this descriptive report, formula (V) may be formula (Va): Petition 870250080967, dated 09 / 09 / 2025, p. 145 / 523 136 / 482 (Va) where LX can be any of the groups (1) to (43) mentioned above in conjunction with formula (Ia); and where G, the Ring QHe XX can assume any of the values ​​revealed here for each of said groups, respectively.

[00628] In addition to the methods described above, the compounds of formulas (I), (II), (III), (IV) and (V) and PROTAC compounds including formula (Ia) can be prepared according to the general procedures and chemical transformations demonstrated in the following experimental section and using standard procedures and knowledge known to a chemist skilled in the art.

[00629] In other embodiments of this descriptive report, compound(s), or a salt thereof, is / are provided, wherein said compound(s) is / are selected from one or more of the Intermediates mentioned below in the experimental section.

[00630] It should be understood that the compound of an Intermediate mentioned below refers to the chemical name of the title mentioned in the experimental section and is in no way limited by the method of preparation nor by whether a given intermediate compound was isolated in the form of a salt and not as a neutral molecule.

[00631] According to a further aspect of the descriptive report, a pharmaceutical composition is provided comprising a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binding unit and (for example, linked to) an AR binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, in association with a pharmaceutically acceptable excipient. Petition 870250080967, dated 09 / 09 / 2025, p. 146 / 523 137 / 482

[00632] According to a further aspect of the descriptive report, a pharmaceutical composition is provided comprising a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binding unit and (for example, linked to) an AR binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, for use in the treatment of cancer.

[00633] According to a further aspect of the descriptive report, a pharmaceutical composition is provided comprising a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binding unit and (for example, linked to) an AR binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, for use in the treatment of a solid tumor.

[00634] According to a further aspect of the descriptive report, a pharmaceutical composition is provided comprising a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binding unit and (for example, linked to) an AR binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, for use in the treatment of a type of AR-sensitive tumor.

[00635] According to a further aspect of the descriptive report, a pharmaceutical composition is provided comprising a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binding unit and (for example, linked to) an AR binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, for use in the treatment of tumor types exhibiting one or more mutated forms of the androgen receptor.

[00636] According to a further aspect of the descriptive report, a pharmaceutical composition comprising a compound of formula (I), [or a PROTAC compound containing a binding unit of Petition 870250080967, dated 09 / 09 / 2025, p. 147 / 523 138 / 482 E3 ubiquitin ligase cereblon and (for example, linked to) an AR-binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, for use in the treatment of prostate cancer (e.g., CRPC, e.g., metastatic CRPC).

[00637] According to a further aspect of the descriptive report, a pharmaceutical composition is provided comprising a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binding unit and (for example, linked to) an AR-binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, for use in the treatment of AR-mutant cancer.

[00638] In any embodiment, aspect or claim herein that mentions cancer without further specificity, further embodiments, aspects or claims may be provided in which said cancer is (or includes) AR+ breast cancer.

[00639] The compositions may be in a form suitable for oral use (for example, as tablets, lozenges, hard or soft capsules, aqueous or oily suspensions, emulsions, dispersible powders or granules, syrups or elixirs) or for parenteral administration (for example, as a sterile aqueous or oily solution for intravenous, subcutaneous or intramuscular dosing). The compositions may be obtained by conventional procedures using conventional pharmaceutical excipients that are well known in the art. Thus, compositions intended for oral use may contain, for example, one or more coloring agents, sweeteners, flavorings and / or preservatives.

[00640] For additional information on formulations, see Chapter 25.2 of Volume 5 of Comprehensive Medicinal Chemistry (Corwin Hansch; Chairman of Editorial Board), Pergamon Press 1990.

[00641] The amount of active ingredient that is combined with one or more excipients to produce a single dosage form will Petition 870250080967, dated 09 / 09 / 2025, page 148 / 523 139 / 482 necessarily vary depending on the host being treated and the specific route of administration.

[00642] The dose size for therapeutic purposes of the compounds in this descriptive report will naturally vary according to the nature and severity of the disease state, the age and sex of the animal or patient, and the route of administration, in accordance with well-known principles of medicine.

[00643] As explained earlier herein, the compounds in this descriptive report may be useful as antitumor agents, in particular as selective inhibitors of the proliferation, survival, motility, dissemination, and invasiveness of mammalian cancer cells, leading to the inhibition of tumor growth and survival and the inhibition of metastatic tumor growth. In particular, the compounds in this descriptive report may be useful as antiproliferative and antiinvasive agents in the containment and / or treatment of solid tumor disease.

[00644] Consequently, the compounds in this descriptive report may be useful in the prevention or treatment of those tumors that are sensitive to androgen receptor degradation and that are involved in the signal transduction steps that lead to the proliferation and survival of tumor cells and the migratory and invasive metastasis capacity of tumor cells. Furthermore, the compounds in this descriptive report may be useful in the prevention or treatment of those tumors that are treatable by androgen receptor degradation; that is, the compounds may be used to produce an androgen receptor degradation effect in a warm-blooded animal in need of such treatment.

[00645] According to a further aspect of the descriptive report, a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binding unit and (for example, linked to) an AR binding unit of formula (Ia)] or a salt Petition 870250080967, dated 09 / 09 / 2025, p. 149 / 523 140 / 482 pharmaceutically acceptable of the same, as defined herein, for use as a medicine.

[00646] According to a further aspect of the descriptive report, a compound of formula (I) is provided, [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binder unit and (for example, linked to) an AR-binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, for use in therapy.

[00647] According to a further aspect of the descriptive report, a compound of formula (I) is provided, [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binder unit and (for example, linked to) an AR-binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, for use in a method of treating the human or animal body by therapy.

[00648] According to a further aspect of the descriptive report, a compound of formula (I) is provided, [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binder unit and (for example, linked to) an AR-binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, for use in producing an antiproliferative effect (for example, in a warm-blooded animal such as a human).

[00649] According to a further aspect of the descriptive report, the use of a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binder unit and (for example, linked to) an AR-binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, is provided for the manufacture of a medicament for the production of an antiproliferative effect (for example, in a warm-blooded animal such as a human). Petition 870250080967, dated 09 / 09 / 2025, p. 150 / 523 141 / 482

[00650] According to a further aspect of the descriptive report, a method is provided for producing an antiproliferative effect in a warm-blooded animal, such as a human, that is in need of such an effect, comprising administering to said animal an effective amount of a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binding unit and (for example, linked to) an AR binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein.

[00651] According to a further aspect of the descriptive report, a compound of formula (I) is provided, [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binder unit and (e.g., linked to) an AR-binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, for use as an anti-invasive agent in the containment and / or treatment of solid tumor disease (e.g., in a warm-blooded animal, such as a human).

[00652] According to a further aspect of the descriptive report, the use of a compound of formula (I), [or a PROTAC compound containing a binding unit of E3 ubiquitin ligase cereblon and (for example, linked to) an AR binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, is provided for the manufacture of a medicament for use as an anti-invasive agent in the containment and / or treatment of solid tumor disease (for example: in a warm-blooded animal, such as a human).

[00653] According to a further aspect of the descriptive report, a method is provided for producing an anti-invasive effect by containing and / or treating solid tumor disease in a warm-blooded animal, such as a human, in need of such an effect, comprising administering to said animal an effective amount of a compound of formula (I), [or a PROTAC compound containing an E3 binding unit] Petition 870250080967, dated 09 / 09 / 2025, p. 151 / 523 142 / 482 ubiquitin ligase cereblon and (for example, linked to) an AR-linking unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein.

[00654] According to a further aspect of the descriptive report, a compound of formula (I) is provided, [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binding unit and (for example, linked to) an AR binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, for use in the prevention or treatment of cancer (for example: in a warm-blooded animal, such as a human).

[00655] According to a further aspect of the descriptive report, the use of a compound of formula (I), [or a PROTAC compound containing a binding unit of E3 ubiquitin ligase cereblon and (for example, linked to) an AR-binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, is provided for the manufacture of a medicament for the prevention or treatment of cancer (for example, in a warm-blooded animal such as a human).

[00656] According to a further aspect of the descriptive report, a method is provided for the prevention or treatment of cancer in a warm-blooded animal, such as a human, in need of such treatment, comprising administering to said animal an effective amount of a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binding unit and (for example, linked to) an AR binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein.

[00657] According to a further aspect of the descriptive report, a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binding unit and (for example, linked to) an AR binding unit of formula (Ia)] or a salt Petition 870250080967, dated 09 / 09 / 2025, p. 152 / 523 143 / 482 pharmaceutically acceptable of the same, as defined herein, for use in the prevention or treatment of solid tumor(s), for example, in a warm-blooded animal such as a human).

[00658] According to a further aspect of the descriptive report, the use of a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binder unit and (for example, linked to) an AR-binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, is provided for the manufacture of a medicament for the prevention or treatment of solid tumor(s) (for example, in a warm-blooded animal, such as a human).

[00659] According to a further aspect of the descriptive report, a method is provided for the prevention or treatment of solid tumor(s) in a warm-blooded animal, such as a human, in need of such treatment, comprising administering to said animal an effective amount of a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binding unit and (for example, linked to) an AR binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein.

[00660] According to a further aspect of the descriptive report, a compound of formula (I) is provided, [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binder unit and (for example, linked to) an AR-binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, for use in the prevention or treatment of types of tumors that are sensitive to androgen receptor degradation.

[00661] According to a further aspect of the descriptive report, the use of a compound of formula (I) is provided, [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binding unit and (for example, linked to) an AR binding unit of formula (Ia)] or a salt Petition 870250080967, dated 09 / 09 / 2025, p. 153 / 523 144 / 482 pharmaceutically acceptable of the same, as defined herein, for the manufacture of a medicament for the prevention or treatment of those types of tumors that are sensitive to androgen receptor degradation.

[00662] According to a further aspect of the descriptive report, a method is provided for the prevention or treatment of those types of tumors that are sensitive to androgen receptor degradation in a warm-blooded animal, such as a human, that are in need of such treatment, comprising administering to said animal an effective amount of a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binding unit and (for example, linked to) an AR binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein.

[00663] As previously explained here, the types of tumors that are sensitive to androgen receptor degradation include prostate cancer (e.g., castration-resistant prostate cancer (CRPC), e.g., metastatic CRPC).

[00664] According to a further aspect of the descriptive report, a compound of formula (I) is provided, [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binding unit and (e.g., linked to) an AR binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, for use in providing a degrading effect on androgen receptors (e.g., in a warm-blooded animal such as a human).

[00665] According to a further aspect of the descriptive report, the use of a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binding unit and (for example, linked to) an AR binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, is provided for the manufacture of a medicament to provide a degrading effect on Petition 870250080967, dated 09 / 09 / 2025, p. 154 / 523 145 / 482 androgen receptors (for example, in a warm-blooded animal, such as a human).

[00666] According to a further aspect of the descriptive report, a method is provided for providing a degrading effect on androgen receptors in a warm-blooded animal, such as a human, that is in need of such an effect, comprising administering to said animal an effective amount of a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binding unit and (for example, linked to) an AR binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein.

[00667] According to a further aspect of the descriptive report, a compound of formula (I) is provided, [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binder unit and (e.g., linked to) an AR-binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, for use in providing a selective degrading effect on androgen receptors (e.g., in a warm-blooded animal such as a human).

[00668] According to a further aspect of the descriptive report, the use of a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binder unit and (for example, linked to) an AR-binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, is provided for the manufacture of a medicament to provide a selective degrading effect on androgen receptors (for example, in a warm-blooded animal such as a human).

[00669] According to a further aspect of the descriptive report, a method is provided for providing a selective degrading effect on androgen receptors in a warm-blooded animal, such as a human, that is in need of such an effect, comprising administering an amount Petition 870250080967, dated 09 / 09 / 2025, p. 155 / 523 146 / 482 effective of a compound of formula (I), [or a PROTAC compound containing a binding unit of E3 ubiquitin ligase cereblon and (for example, linked to) an AR binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein.

[00670] According to a further aspect of the descriptive report, a compound of formula (I) is provided, [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binder unit and (for example, linked to) an AR-binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, for use in the treatment of tumor types exhibiting mutations in the androgen receptor.

[00671] According to a further aspect of the descriptive report, the use of a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binder unit and (for example, linked to) an AR-binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, is provided for the manufacture of a medicament for the prevention or treatment of those types of tumors that exhibit mutations in the androgen receptor.

[00672] According to a further aspect of the descriptive report, a method is provided for the prevention or treatment of those types of tumors exhibiting mutations in the androgen receptor in a warm-blooded animal, such as a human, that are in need of such prevention or treatment, comprising administering to said animal an effective amount of a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binding unit and (for example, linked to) an AR binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein.

[00673] As mentioned above, the types of tumors known to exhibit mutations in the androgen receptor include prostate tumors and, Petition 870250080967, dated 09 / 09 / 2025, page 156 / 523 147 / 482 therefore, prostate cancer, castration-resistant prostate cancer (CRPC) and metastatic CRPC).

[00674] According to a further aspect of the descriptive report, a compound of formula (I) is provided, [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binder unit and (e.g., linked to) an AR-binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, for use in the treatment of prostate cancer (e.g., castration-resistant prostate cancer (CRPC), e.g., metastatic CRPC).

[00675] According to a further aspect of the descriptive report, the use of a compound of formula (I), [or a PROTAC compound containing a cereblon ubiquitin ligase E3 binding unit and (e.g., linked to) an AR binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein, is provided for the manufacture of a medicament for the treatment of prostate cancer (e.g., castration-resistant prostate cancer (CRPC), e.g., metastatic CRPC).

[00676] According to a further aspect of the descriptive report, a method is provided for the treatment of prostate cancer (e.g., castration-resistant prostate cancer (CRPC), e.g., metastatic CRPC) in a warm-blooded animal, such as a human, in need of such treatment, comprising administering to said animal an effective amount of a compound of formula (I), [or a PROTAC compound containing an E3 ubiquitin ligase cereblon binding unit and (e.g., linked to) an AR binding unit of formula (Ia)] or a pharmaceutically acceptable salt thereof, as defined herein.

[00677] In a modality where cancer is mentioned here, the cancer in question is prostate cancer. Petition 870250080967, dated 09 / 09 / 2025, page 157 / 523 148 / 482

[00678] In a modality where cancer is mentioned here, the said cancer is CRPC.

[00679] In a modality where cancer is mentioned here, the said cancer is metastatic CRPC. General experimental conditions and abbreviations

[00680] The following abbreviations are used: AcOH = acetic acid; AIBN = 2,2'-azobis(2-methylpropionitrila); aq. = watery; Boc = butoxycarbonyl; Brettphos = 2-(dicyclo-hexylphosphine)3,6-dimethoxy-2',4',6'-tri-isopropyl-1,1' biphenyl; Brettphos Pd G3 = Metanosulfonate de [(2-di-cyclo-hexylphosfino-3,6dimethoxy-2',4',6'-tri-isopropyl-1,1 '-biphenyl)-2-(2'-amino-1,1 'biphenyl)]paládio(II); tert-butylBrettPhos = Di-tert-butyl(2',4',6'-tri-isopropyl-3,6dimethoxy-[1,1'-biphenyl]-2-yl)phosphine; tert-BuOH = tert -butanol; CDI = 1,1'carbonyldiimidazole; CPhos = 2-dicyclohexylphosphino-2',6'-bis(N,Ndimethylamino)biphenyl; Dave-phos-Pd G3 = 2-dicyclohexylphosphino-2-(N,N-dimethylamino)biphenyl(2 '-amino-1,1 '-biphenyl-2-yl)paládium(II) methanesulfonate; DCM = dichloromethane; DEA = Diethylamine; DIAD = Diisopropyl azodicarboxylate; DIPEA = N,N-di-isopropylethylamine; Cbz = carboxibenzila; DMAP = 4-(dimethylamino)pyridine;DessMartin periodinane = 3-oxo-115-benzo[d][1,2]iodaoxol-1,1,1(3#)-tri-yl triacetate; DMF = N,N-dimethylformamide; DMSO = dimethyl sulfoxide; EdC = (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride); Ephos = dicyclohexyl(3-isopropoxy-2',4',6'-triisopropyl-[1,1'-biphenyl]-2-yl)phosphane; Et2O = diethyl ether; EtOAc = ethyl acetate; EtOH = ethanol; FSC = flash chromatography on silica; h = hour(s); HATU = Hexafluorophosphate of (1(bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium3-oxide); HOBt = Hydroxybenzotriazole; HPLC = High-performance liquid chromatography; IPA = Isopropyl alcohol; LHMDS = Lithium bis(trimethylsilyl)amide; MeCN = Acetonitrile; MeOH = Methanol; min = minutes; m / z = Mass-to-charge ratio observed for the main mass spectrometry peak(s); MTBE = Petition 870250080967, dated 09 / 09 / 2025, page 158 / 523 149 / 482 methyl tert-butyl ether 2-MeTHF = 2-methyltetrahydrofuran; NBS = N bromosuccinimide; NMP = N-methyl-2-pyrrolidone; NMR = nuclear magnetic resonance; [Pd(cinnamyl)Cl]2 = Dichlorobis[(1,2,3-)-1-phenyl-2-propenyl]dipalladium(II); PdCl2(dtbpf) = [1,1'-Bis(di-tert butylphosphino)ferrocene]dichloropalladium(II); Pd2(dba)3 = tris(dibenzylideneacetone)dipalladium; PdCb(PPh3)2 = Bis(triphenylphosphine)palladium(II) dichloride; Pd-PEPPSI-IHeptCl= dichloro[1,3-bis(2,6-di-4heptylphenyl)imidazol-2-yldieno(3-chloropyridyl)palladium(II); Pd-PEPPSI-IPent = dichloro[1,3-bis(2,6-Di-3-pentylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium (II), Pd(dppfhCl2-DCM = 1,1'bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex; Pd(dppf)Cl2 = [1,1 'Bis(diphenylphosphino)ferrocene]dichloropalladium(II); Pd( t-Bu3P)2 = Bis(tri-tert-butylphosphine)palladium(O); RockPhos = 2-di( tert-butyl)phosphino-2',4',6'-tri-isopropyl3-methoxy-6-methylbiphenyl;RockPhos Pd G3 = [(2-di-tert-butylphosphino-3-methoxy-6-methyl-2',4',6'-tri-isopropyl-1,r-biphenyl)-2-(2aminobiphenyl)]paládium(II) methanesulfonate; RT = room temperature (~17 to 25 °C); RuPhos = 2-dicyclo-hexylphosphino-2',6'-di-isopropoxybiphenyl; RuPhos Pd G3 = (2-dicyclo-hexylphosphino-2',6'-di-iso-propoxy-1,1'biphenyl)(2'-amino-1,1'-biphenyl-2-yl)-paládium(II) methanesulfonate; TFA = trifluoroacetic acid; THF = tetrahydrofuran; sat. = saturated; CFS = supercritical fluid chromatography; S Phos = 2-dicyclo-hexylphosphino-2,6-di-methyloxy-1,1-biphenyl; Xanthos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; XPhos = 2-dicyclohexylphosphino-2',4',6'-tri-isopropylbiphenyl.;

[00681] NMR was performed at 300 to 500 MHz in deuterated DMSO and at a temperature of 20 to 30 °C, unless otherwise indicated. The following standard abbreviations are used for NMR data: s = singlet, d = doublet, m = multiplet, br = wide, dd = doublet of doublets, q = quartet, dt = doublet of triplets, etc. Petition 870250080967, dated 09 / 09 / 2025, p. 159 / 523 150 / 482

[00682] Preparatory reversed-phase HPLC (RP HPLC) using decreasingly polar mixtures of eluents (e.g., water and MeCN) can typically involve a gradient over 10 to 20 minutes, at 40 to 50 ml per minute, from a 95:5 solvent mixture to a 5:95 mixture. The following column and eluent conditions are used here: Column A: Waters XSelect CSH C18 ODB column, 5 µm silica, 30 mm diameter, 100 mm length Eluent A: Decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN. Eluent B: Mixtures of decreasingly polar water (containing 0.1% NH3) and MeCN.

[00683] After HPLC (which often involves the presence of formic acid or trifluoroacetic acid in the eluent), the fractions containing the desired product were, in some cases, treated with a suitable base as part of a further processing step in order to ensure the release of the title compound as a neutral molecule rather than a salt, consequently, when “Basic Processing A” is mentioned: the fractions containing the desired compound were concentrated to remove MeCN. The resulting fractions, mostly aqueous, were basified with NaHCO3 solution (e.g., 50 ml) and extracted in DCM (e.g., 3 x 100 ml). The combined organic solutions were washed with NaCl solution (e.g., 100 ml), dried (e.g., with Na2SO4 or MgSO4) and concentrated to yield the title compound.

[00684] Concentration / Evaporation: when solutions or mixtures are described as concentrated or evaporated, this is usually performed in a rotary evaporator under reduced pressure using a warm or hot water bath. Petition 870250080967, dated 09 / 09 / 2025, page 160 / 523 151 / 482

[00685] Salts: When certain compounds have been obtained as an acid addition salt, for example, a monochloride salt or a bischloride salt, the stoichiometry of the salt is presumed, based on the number and nature of the basic groups in the compound, and may not have been determined experimentally, for example, by means of elemental analysis data.

[00686] Chemical nomenclature: In general, examples and intermediate compounds were named using ACD Name, “Structure to Name” part of ChemDraw Ultra (CambridgeSoft) or Biovia Draw 2016. Example 1: Intermediate 1a: 7-bromo-4-chloro-1H-indol

[00687] 1-bromo-4-chloro-2-nitrobenzene (7 x 100 g, 422.9 mmol) was added to THF (7 x 700 ml) followed by dropwise addition of vinylmagnesium bromide (1 M, 7 x 1.69 l) at -60 °C and the mixture was stirred for 1 h. NH4Cl (aq, 2.0 l) was added to the solution at 0 °C and the product mixtures were combined and extracted over EtOAc (2.0 l). The organic layer was washed with NaCl solution (1.0 l) and the solvent was evaporated to dryness to yield the crude product which was purified by column chromatography, Et2O:EtOAc gradient elution at 10 to 25% to yield the title compound (260 g, 34%) as a yellow solid. 'H (CDCb) NMR δ 6.64 (1H, s), 6.93 (1H, m), 7.18 (2H, m), 8.35 (1H, s). Intermediate 1b: 7-bromo-4-chloro-1 H-indole-3-carbonitrile Petition 870250080967, dated 09 / 09 / 2025, p. 161 / 523 152 / 482

[00688] 7-bromo-4-chloro-1H-indol (4 x 70.0 g, 303.7 mmol) was added to MeCN (4 x 560 ml), followed by dropwise addition of chlorosulfonyl isocyanate (4 x 51.6 g, 364.4 mmol, 4 x 31.6 ml) at 0 °C and stirred for 2 h. DMF (4 x 266.0 g, 3.64 mol, 4 x 280.0 ml) was then added dropwise and the solution was kept under stirring at 0 °C for 2 h, then at room temperature for 16 h. Water was added dropwise at 10 °C until a solid formed, which was isolated by filtration. The batches of solids were combined and ground with Et2O:EtOAc:DCM (4:1:1) to yield the title compound (105.0 g, 33.3%) as a white solid. 1H NMR δ 7.22 - 7.24 (1H, d, J=8.4 Hz), 7.50 to 7.52 (1H, d, J=8.4 Hz), 8.46 (1H, s); m / z: ES+[M+H]+= 255.1. Intermediate 1c: Benzyl 4-(4-bromophenyl)piperidine-1-carboxylate

[00689] Benzyl carbon chloride (14.27 ml, 96.17 mmol) was added dropwise over 5 minutes to a solution of 4-(4-bromophenyl)piperidine (25.0 g, 100.98 mmol) and DIPEA (42.0 ml, 240.43 mmol) in 2-MeTHF (250 ml) at 0 °C. The resulting mixture was stirred at room temperature for 24 h, then rapidly cooled with water (250 ml). The layers were separated, and the organic layer was washed with water (250 ml), NaCl solution (50 ml), dried with MgSO4, filtered, and evaporated to yield the crude product as a colorless oil. The oil was diluted with IPA:water (1:1, 200 ml) and stirred at room temperature for 1 h. The resulting solid was collected by filtration, washed with water (2 x 20 ml) and dried under vacuum at 50 °C for 16 h to yield the title compound (32.9 g, 91%) as a white solid. 1H NMR δ 1.50 (2H, qd), 1.75 (2H, d), 2.72 (1H, m), 2.90 (2H, s), 4.14 (2H, d), 5.10 (2H, s), 7.18 - 7.26 (2H, m), 7.29 - 7.44 (5H, m), 7.45 - 7.53 (2H, m). Intermediate 1d: Petition 870250080967, dated 09 / 09 / 2025, p. 162 / 523 153 / 482 Benzyl 4-{4-[4-(1,3-dioxolan-2-yl)piperidin-1-yl]phenyl}piperidine-1-carboxylate

[00690] 4-(1,3-dioxolan-2-yl)piperidine (15.02 g, 95.52 mmol), benzyl 4-(4-bromophenyl)piperidine-1-carboxylate (32.5 g, 86.83 mmol) and CS2CO3 (56.6 g, 173.67 mmol) in 1,4-dioxane (325 ml) under nitrogen was added tri-tert-butylphosphonium tetrafluoroborate (2.52 g, 8.68 mmol). The mixture was degassed with nitrogen followed by the addition of Pd(t-Bu3P)2 (2.21 g, 4.34 mmol). The resulting mixture was stirred at 100 °C for 20 h, cooled to room temperature, and the solid was filtered under vacuum. The solid was washed with 1,4-dioxane (3 x 65 ml) and the filtrate was evaporated to produce a pale yellow solid. The solid was suspended in cyclopentyl methyl ether:heptane (1:10, 300 ml), stirred at 50 °C for 30 min and then allowed to cool at room temperature for a further 2 h. The solid was filtered to yield the title compound (28.9 g, 73.9%) as a solid cream.1H NMR δ 1.43 (4H, m), 1.57 - 1.67 (1H, m), 1.73 (4H, m), 2.54 2.63 (3H, m), 2.89 (2H, s), 3.65 (2H, m), 3.75 - 3.93 (4H, m), 4.13 (2H, m), 4.61 (1H, d), 5.09 (2H, s), 6.85 (2H, m), 7.06 (2H, m), 7.29 - 7.44 (5H, m); m / z: ES+[M+H]+= 451.5. Intermediate 1e: 4-(1,3-dioxolan-2-yl)-1-[4-(piperidin-4-yl)phenyl]piperidine

[00691] 4-{4-[4-(1,3-dioxolan-2-yl)piperidin-1-yl]phenyl}piperidine-1-carboxylate benzyl (762 mg, 1.69 mmol) was dissolved in EtOH (20 ml) and Pd / C (10%, 180 mg, 0.17 mmol) was added under nitrogen. The reaction was Petition 870250080967, dated 09 / 09 / 2025, p. 163 / 523 154 / 482 stirred under a hydrogen atmosphere at 4 bar for 16 h. The catalyst was then filtered through a Celite® pad, the solvent was removed under reduced pressure and azeotropated with excess MeCN. The product was dried in a vacuum oven for 2 h to yield the title compound (449 mg, 84%) as a waxy white solid. 1H NMR δ 1.33 - 1.51 (4H, m), 1.54 - 1.68 (3H, m), 1.72 (2H, d), 2.4 - 2.46 (1H, m), 2.54 - 2.64 (4H, m), 3.01 (2H, d), 3.64 (2H, d), 3.74 3.94 (4H, m), 4.61 (1H, d), 6.85 (2H, d), 7.04 (2H, d); m / z: ES+[M+H]+= 317.7. Intermediate 1f: 4-chloro-7-(4-{4-[4-(1,3-dioxolan-2-yl)piperidin-1-yl]phenyl}piperidin-1-yl)-1 Hindol-3-carbonitrile

[00692] [Pd(cinnamyl)Cl]2 (0.218 g, 0.42 mmol) and CPhos (0.735 g, 1.68 mmol) were added to a degassed mixture of 4-(1,3-dioxolan-2-yl)-1-[4-(4-piperidyl)phenyl]piperidine (11.72 g, 37.03 mmol) and 7-bromo-4-chloro-1H-indol-3-carbonitrile (intermediate 1b) (8.6 g, 33.66 mmol) in 2MeTHF (86 ml). LHMDS (1 M in THF, 118 ml, 117.81 mmol) was added dropwise and the reaction was stirred at 50 °C for 1.5 h. The reaction was allowed to cool to room temperature, diluted with water (200 ml) and stirred for 10 min. A precipitate formed, positioned between the two layers. This solid was collected by filtration, washed with water (25 ml) and dried in a vacuum oven at 50 °C overnight to yield the title compound (13.95 g, 84%) as a creamy solid.RMN de 1H δ 1.39 (2H, m), 1.56 - 1.67 (1H, m), 1.67 - 1.78 (2H, m), 1.83 (2H, m), 1.88 - 2.03 (2H, m), 2.58 (3H, td), 2.71 - 2.82 (2H, m), 3.42 (2H, d), 3.66 (2H, d), 3.72 - 3.82 (2H, m), 3.82 - 3.91 (2H, m), 4.60 (1H, d), 6.83 (1H, d), 6.88 (2H, d), 7.04 - 7.21 (3H, m), 8.28 (1H, s), 12,21 (1H, s); m / z: ES+[M+H]+= 491,5. Intermediário 1g: Petition: 870250080967, on September 9, 2025, page. 164 / 523 155 / 482 4-chloro-7-{4-[4-(4-formilpiperidin-1-il)fenil]piperidin-1-il}-1 H-indol-3carbonitrila

[00693] HCl (2 M, 274 ml, 547.83 mmol) was added in portions to a suspension of 4-chloro-7-(4-{4-[4-(1,3-dioxolan-2-yl)piperidin-1-yl]phenyl}piperidin-1-yl)-1H-indol-3-carbonitrile (13.45 g, 27.39 mmol) in THF (135 ml) at room temperature. The resulting solution was stirred at 60 °C for 4 h. The resulting solution was accumulated in an ice bath and neutralized with NaOH (2 M, 180 ml) to pH 7. The product was filtered and the solid was washed with water (20 ml) and dried under vacuum to yield the title compound (12.85 g) as a creamy solid which was used without further purification. 1H NMR δ 1.64 (2H, s), 1.83 (2H, d), 1.88 - 2.06 (4H, m), 2.71 - 2.92 (4H, m), 3.40 (3H, d), 3.51 - 3.62 (3H, m), 6.85 (1H, d), 6.99 (2H, s), 7.15 (3H, d), 8.30 (1H, d), 9.63 (1H, s), 12.25 (1H, s); m / z: ES+[M+H]+= 447.4. Intermediate 1h: 3-(5-bromo-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione

[00694] DIPEA (25 ml, 143.52 mmol) was added to methyl 4-bromo-2(bromomethyl)benzoate (14.65 g, 47.57 mmol) and 3-aminopiperidine-2,6-dione hydrochloride (11.74 g, 71.35 mmol) in MeCN (200 ml) under nitrogen. The resulting suspension was stirred at 80 °C for 48 h. The reaction mixture was cooled to room temperature and filtered. The solid was washed with MeCN (60 ml), MeCN:Et2U (2:3, 50 ml) and Et2U (2 x 50 ml) to yield the title compound (13.1 g, 85%) as a dark blue solid; 1H NMR δ 1.95 - 2.08 (1H, m), 2.34 - 2.46 (1H, m), 2.57 - 2.65 (1H, m), 2.91 (1H, m), 4.35 (1H, d), 4.48 (1H, d), 5.11 (1H, dd), 7.67 (1H, d), 7.72 (1H, dd), 7.83 - 7.96 (1H, m), 10.98 (1H, s). m / z: ES+[M+H]+= 323.0. Petition 870250080967, dated 09 / 09 / 2025, p. 165 / 523 156 / 482 Intermediate 1i: 4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-yl]piperazine-

[00695] CS2CO3 (57.4 g, 176 mmol) and Pd-PEPPSI-IPent (2.33 g, 2.94 mmol) were added in a portion to a degassed solution of tert-butyl piperazine-1-carboxylate (14.22 g, 76.36 mmol) and 3-(5-bromo-1oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione (19.0 g, 58.74 mmol) in 1,4-dioxane (590 ml) under nitrogen. The resulting mixture was stirred at 90 °C for 24 h. The reaction mixture was cooled to room temperature, diluted with DCM (1 l) and washed sequentially with 5% AcOH in water (500 ml) and NaCl solution (500 ml). The organic layer was dried with MgSO4, filtered, and evaporated to produce the crude product.The crude product was ground with EtOAc (250 ml), the solid collected by filtration, washed with Et2O (100 ml) and vacuum dried to yield the title compound (22.1 g, 88%) as a gray solid; 1H NMR δ 1.43 (9H, s), 1.96 (1H, d), 2.31 - 2.41 (1H, m), 2.59 (1H, d), 2.87 (1H, s), 3.29 (4H, d), 3.47 (4H, d), 4.22 (1H, d), 4.34 (1H, d), 5.05 (1H, dd), 7.07 (2H, d), 7.54 (1H, d), 10.92 (1H, s); m / z: ES+[M+H]+= 429.2. Intermediate 1j: 3-[1-oxo-5-(piperazin-1-yl)-1,3-dihydro-2H-isoindol-2yl]piperidine-2,6-dione hydrochloride HCl

[00696] A 4 M HCl solution in 1,4-dioxane (8.75 ml, 35.0 mmol) was added to tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro1H-]isoindol-5-yl]piperazine-1-carboxylate (1.50 g, 3.50 mmol) Petition 870250080967, dated 09 / 09 / 2025, p. 166 / 523 157 / 482 in 1,4-dioxane (2 ml) at room temperature. The reaction was stirred at room temperature for 1 h. EtOAc (5 ml) was added and the reaction mixture was stirred for 10 min. The resulting precipitate was collected by filtration and the solid washed with EtOAc (2 x 5 ml) and then dried under vacuum to yield the title compound (1.08 g, 85%) as a dark gray solid (HCl salt); 1H-NMR 5.06 (1H, dd), 7.11 - 7.18 (2H, m), 7.59 (1H, d), 9.17 (2H, s), 10.93 (1H, s); m / z: ES+[M+H]+= 329.0. Example 1: 4-Chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 Hisoindol-5-yl]piperazin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-1 Hindol-3-carbonitrile

[00697] 4-chloro-7-{4-[4-(4-formylpiperidin-1-yl)phenyl]piperidin-1-yl}1H-indol-3-carbonitrile (intermediate 1g) (9.3 g, 20.81 mmol) and 3-[1-oxo-5-(piperazin-1-yl)-1,3-dihydro-2H-isoindol-2-yl]piperidine-2,6-dione hydrochloride (intermediate 1j) (7.97 g, 21.85 mmol) were stirred in MPN (65.0 ml) at TA followed by DIPEA (3.81 ml, 21.85 mmol). After stirring for 5 h, sodium triacetoxyborohydride (5.29 g, 24.97 mmol) was added in a portion and stirred at TA for 30 min. The reaction was rapidly cooled with water (260 ml), stirred for 30 min, and then vacuum filtered. The solid was washed with water (10 ml) and dissolved in IPA:DCM (1:3, 720 ml), washed with NaHCO3 solution (180 ml), NaCl solution (180 ml), dried with MgSO4, and filtered to produce the crude product. The crude product was purified by flash chromatography on silica gel, gradient elution of EtOAc from 50 to 100%. Petition 870250080967, dated 09 / 09 / 2025, p. 167 / 523 158 / 482 in heptane, followed by 0 to 7% MeOH in DCM to produce a creamy solid. The solid was suspended in MeCN (65 ml) and stirred at 80 °C for 1 h. The suspension was allowed to cool to room temperature for 16 h and was vacuum filtered to yield the title compound (6.06 g, 38.4%) as a white solid. 1H NMR δ 1.17 - 1.29 (2H, m), 1.64 - 1.74 (1H, m), 1.83 (4H, br t), 1.91 - 2.02 (3H, m), 2.23 (2H, br d), 2.31 - 2.43 (2H, m), 2.51 - 2.54 (4H, m), 2.54 - 2.66 (4H, m), 2.78 (2H, br d), 2.85 - 2.95 (1H, m), 3.29 - 3.31 (4H, m), 3.42 (2H, br d), 3.64 (2H, br d), 4.21 (1H, d), 4.33 (1H, d), 5.05 (1H, dd), 6.86 (1H, d), 6.91 (2H, d), 7.05 - 7.08 (1H, m), 7.07 (1H, s), 7.13 (2H, br d), 7.16 (1H, d), 7.53 (1H, d), 8.32 (1H, s), 10.94 (1H, s), 12.26 (1H, br s); m / z (ES+) [M+H]+ = 759.8. Example 2 Intermediate 2a: 7-bromo-4-fluoro-1H-indol

[00698] 1-bromo-4-fluoro-2-nitrobenzene (6 x 100.0 g, 454 mmol) was dissolved in THF (6 x 700.0 mL) at -45 °C followed by dropwise addition of vinylmagnesium bromide (1 M, 6 x 1.82 L) under nitrogen and stirred for 30 min. NH4Cl (aq, 2.0 L) was added to the solution and the 6 batches were combined. The THF was evaporated and the product was extracted with EtOAc (9.0 L), washed with NaCl solution (1.0 L), dried with Na2SO4, filtered and the solvent evaporated. The crude product was purified by column chromatography, Et2O:EtOAc gradient elution at 0 to 20% to yield the title compound (148.5 g, 24.3%) as a brown oil; 1H NMR δ 6.64 (1H, s), 6.78 (1H, m), 7.27 (1H, m), 7.45 (1H, s), 11.65 (1H, s). Intermediate 2b: 7-bromo-4-fluoro-1 H-indole-3-carbonitrile Petition 870250080967, dated 09 / 09 / 2025, p. 168 / 523 159 / 482

[00699] 7-bromo-4-fluoro-1H-indol (140.0 g, 654 mmol) was added to MeCN (848 ml) followed by chlorosulfonyl isocyanate (111.1 g, 785 mmol, 68.2 ml) by dropwise at 0 °C and stirred for 2 h. DMF (574.0 g, 7.85 mol, 604 ml) was added by dropwise to the solution at 0 °C and stirred for a further 2 h. Water (1.6 l) was added and the resulting solid was washed with water (100.0 ml) to obtain a yellow solid. The yellow solid was extracted in EtOAc (500.0 ml), dried with Na2SO4 and concentrated under reduced pressure. The crude product was ground with Et2O:EtOAc (4:1, 800.0 ml) to yield the title compound (100.78 g, 62.9%) as a yellow solid. 1H NMR δ 7.03 (1H, m), 7.50 (1H, m), 8.40 (1H, m), 12.77 (1H, s); m / z: ES-[MH]-= 237.0. Intermediate 2c: 7-(4-{4-[4-(1,3-dioxolan-2-yl)piperidin-1-yl]phenyl}piperidin-1-yl)-4-fluoro-1 Hindol-3-carbonitrile

[00700] [Pd(cinnamyl)Cl]2 (0.068 g, 0.13 mmol), CPhos (0.228 g, 0.52 mmol), 4-(1,3-dioxolan-2-yl)-1-[4-(piperidin-4-yl)phenyl]piperidine, intermediate 1e (3.64 g, 11.50 mmol) and 7-bromo-4-fluoro-1H-indol-3carbonitrile, intermediate 2b (2.5 g, 10.46 mmol), were degassed in 2-MeTHF (25 ml) for 10 min. LHMDS (1 M in THF, 36.6 ml, 36.60 mmol) was added in a portion and the reaction was stirred at 50 °C for 1.5 h. The reaction mixture was then cooled to room temperature, diluted with water (65 ml) and stirred for 10 min. A precipitate formed between the two layers was collected by filtration and washed with water (25 ml) and dried in a vacuum oven at 50 °C for 16 h to yield the title compound (3.41 g, 68.7%) as a creamy solid. 1H NMR δ 1.39 (2H, qd), 1.56 Petition 870250080967, dated 09 / 09 / 2025, p. 169 / 523 160 / 482 1.67 (1H, m), 1.67 - 1.77 (2H, m), 1.77 - 1.86 (2H, m), 1.94 (2H, qd), 2.52 2.64 (3H, m), 2.68 - 2.8 (2H, m), 3.36 (2H, d), 3.66 (2H, d), 3.72 - 3,91 (4H, m), 4,60 (1H, d), 6,80 (1H, dd), 6,85 - 6,94 (3H, m), 7,12 (2H, d), 8,24 (1H, s), 12,19 (1H, s); m / z: ES+[M+H]+= 475,5. Intermediário 2d: 4-fluoro-7-{4-[4-(4-formilpiperidin-1-il)fenil]piperidin-1-il}-1 H-indol-3carbonitrila

[00701] To a stirred suspension of 7-(4-{4-[4-(1,3-dioxolan-2yl)piperidin-1-yl]phenyl}piperidin-1-yl)-4-fluoro-1H-indol-3-carbonitrile (3.41 g, 7.19 mmol) in THF (34.0 ml) at TA, HCl (2 M, 71.9 ml, 143.71 mmol) was added. The mixture was stirred at 60 °C for 2.5 h, cooled in an ice bath, and neutralized with NaOH (2 M) until pH 7 was reached. The mixture was extracted with 2-MeTHF (2 x 100 ml), then the organic extracts were washed with NaCl:water solution (1:1, 50 ml), dried by passing through a phase separation cartridge, filtered, and evaporated to produce the crude product. The crude product was suspended in MeCN (50 ml) at 80 °C for 1 h, then cooled to room temperature over 16 h. The solid was collected by filtration, washed with excess MeCN, and dried under vacuum at 45 °C to yield the title compound (2.45 g, 79%) as a creamy solid.RMN de 1H δ 1.53 - 1.66 (2H, m), 1.78 - 1.88 (2H, m), 1.88 - 2.03 (4H, m), 2.43 - 2.48 (1H, m), 2.53 - 2.63 (1H, m), 2.7 - 2.85 (4H, m), 3.37 (2H, d), 3.55 (2H, dt), 6.82 (1H, dd), 6.87 6.96 (3H, m), 7.14 (2H, d), 8.26 (1H, d), 9.64 (1H, d), 12.23 (1H, s); m / z: ES[MH]-= 429,3. Example 2: 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-il)-1-oxo-2,3-di-hydro-1 H-isoindol-5il]piperazin-1 -il}metil)piperidin-1-il]fenil}piperidin-1 -il)-4-fluoro-1 H-indol3-carbonitrila Petition: 870250080967, on September 9, 2025, page. 170 / 523 161 / 482

[00702] 4-fluoro-7-{4-[4-(4-formylpiperidin-1-yl)phenyl]piperidin-1-yl}1H-indol-3-carbonitrile (3.46 g, 8.04 mmol) and 3-[1-oxo-5-(piperazin-1-yl)-1,3dihydro-2H-isoindol-2-yl]piperidine-2,6-dione HCl, intermediate 1j (3.08 g, 8.44 mmol), were suspended in DCM (25.0 ml) and IPA (8.3 ml) at room temperature. DIPEA (1.47 ml, 8.44 mmol) was added and the suspension was stirred at room temperature for 2 h. Sodium triacetoxyborohydride (2.04 g, 9.64 mmol) was then added and the suspension was stirred at room temperature for 5 min. The reaction mixture was diluted with IPA:DCM (1:3, 135 ml), washed with water (70 ml), NaHCO3 solution (70 ml), NaCl solution (75 ml) and dried by passing through a phase separation cartridge. The solvent was evaporated to yield the crude product and purified by flash chromatography on silica, gradient elution of 50 to 100% EtOAc in heptane followed by 0 to 10% MeOH in DCM.The fractions were evaporated and the product was stirred in MeCN (35 ml) at 80 °C for 1 h, then cooled to room temperature for 16 h. The solid was collected by filtration, washed with MeCN (10 ml) and dried under vacuum at 45 °C to yield the title compound (3.5 g, 58.6%) as a creamy solid. 1H NMR δ 1.16 - 1.3 (2H, m), 1.63 - 1.75 (1H, m), 1.76 - 1.88 (4H, m), 1.9 - 2.03 (3H, m), 2.23 (2H, d), 2.31 - 2.42 (1H, m), 2.52 (4H, d), 2.54 - 2.68 (4H, m), 2.71 - 2.81 (2H, m), 2.85 2.96 (1H, m), 3.31 (4H, s), 3.37 (2H, d), 3.64 (2H, d), 4.21 (1H, d), 4.33 (1H, d), 5.05 (1H, dd), 6.82 (1H, dd), 6.86 - 6.97 (3H, m), 7.06 (2H, d), 7.13 (2H, d), 7.52 (1H, d), 8.26 (1H, s), 10.93 (1H, s), 12.23 (1H, s); m / z: ES+[M+H]+= 743.5. Examples 3 and 4 Petition 870250080967, dated 09 / 09 / 2025, p. 171 / 523 162 / 482

[00703] The enantiomers of 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3yl)-1-oxo-2,3-dihydro-1H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1yl]phenyl}piperidin-1-yl)-4-fluoro-1H-indol-3-carbonitrile (example 2) (30 mg, 0.04 mmol) were separated on a Sepiatec 100 CFS using Regis (R,R) Whelk-01 CFS conditions, 21.1 x 250 mm, 5 microns, 50% MeOH / MeCN 3:7 / 50% scCO2 at a flow rate of 60 ml / min, 40 °C to yield, in order of elution, example 3 (isomer 1, 9.0 mg, 30.0%) and example 4 (isomer 2, 7.2 mg, 24.0%) as white solids. Example 3: 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5yl]piperazin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-4-fluoro-1H-indol3-carbonitrile [absolute stereochemistry not yet confirmed]

[00704] RMN of 1H δ 1.17 - 1.31 (2H, m), 1.64 - 1.76 (1H, m), 1.78 1.88 (4H, m), 1.89 - 2.03 (3H, m), 2.23 (2H, d), 2.34 - 2.4 (1H, m), 2.51 - 2.53 (4H, m), 2.53 - 2.55 (1H, m), 2.55 - 2.59 (1H, m), 2.61 (2H, d), 2.71 - 2.81 (2H, m), 2.84 - 2.96 (1H, m), 3.25 - 3.31 (4H, m), 3.37 (2H, d), 3,64 (2H, d), 4.16 - 4.37 (2H, m), 5.04 (1H, dd), 6.82 (1H, dd), 6.87 - 6.96 (3H, m), 7.02 7.09 (2H, m), 7.13 (2H, d), 7.52 (1H, d), 8.26 (1H, d), 10,93 (1H, s), 12,23 (1H, s); m / z: ES+[M+H]+= 743,5; >99% de ee. Example 4: 7-(4-{4-[4-({4- [2-(2,6-dioxopiperidin-3-il)-1-oxo-2,3-di-hydro-1 H-isoindol-5il]piperazin-1 -il}metil)piperidin-1-il]fenil} piperidin-1 -il)-4-fluoro-1 H-indol3-carbonitrila [estereoquímica absolute but not confirmed] Petition: 870250080967, on September 9, 2025, page. 172 / 523 163 / 482

[00705] RMN de 1H δ 1,24 (3H, s), 1,63 - 1,76 (1H, m), 1,77 - 1,88 (4H, m), 1,89 - 2,03 (3H, m), 2,23 (2H, d), 2,34 - 2,4 (1H, m), 2,51 - 2,56 (4H, m), 2,55 - 2,59 (1H, m), 2,59 - 2,65 (2H, m), 2,71 - 2,81 (2H, m), 2,84 - 2,96 (1H, m), 3,30 (4H, s), 3,34 - 3,41 (2H, m), 3,6 - 3,68 (2H, m), 4,16 - 4,38 (2H, m), 5,04 (1H, dd), 6,82 (1H, dd), 6,88 - 6,96 (3H, m), 7,03 - 7,09 (2H, m), 7,13 (2H, d), 7,52 (1H, d), 8,26 (1H, d), 10,93 (1H, s), 12,24 (1H, s); m / z: ES+[M+H]+= 743,5; >99 % de ee. Exemplo 5 Intermediário 5a: 4-(4-nitro-1 H-indol-1 -il)piperidina-1-carboxilato de ter-butila

[00706] 4-nitro-1H-indol (5 x 95.0 g, 585 mmol), tert-butyl 4[(methanesulfonyl)oxy]piperidine-1-carboxylate (5 x 409.0 g, 1.46 mol) and Cs2CÜ3 (5 x 573.0 g, 1.76 mol) were added to DMF (1.5 l). The solution was degassed with nitrogen and stirred at 80 °C for 12 h. Water (10.0 l) was added to each mixture and the batches were combined by extraction with EtÜAc (6.0 l). The organic layer was washed with NaCl solution (10.0 l x 3) and dried with Na2SÜ4. The solvent was evaporated and the crude product was purified by recrystallization of MTBE:Et2O (1:4, 500.0 ml) at room temperature for 20 min. The solid was filtered and dried under vacuum to yield the title compound (910.0 g) as a brown solid. 1H NMR δ 1.39 (s, 9H), 1.82-1.93 Petition 870250080967, dated 09 / 09 / 2025, p. 173 / 523 164 / 482 (m, 4H), 2.85 (s, 2H), 4.08-4.11 (m, 2H), 4.69-4.75 (m, 1H), 7.02 (d, J = 3.2 Hz, 1H), 7.32 (t, J = 8.4 Hz, 1H), 7.92 (d, J = 3.6 Hz, 1H), 8.05 (d, J = 7.6 Hz, 1H), 8.13 (d, J = 8.4 Hz, 1H). Intermediate 5b: tert-butyl 4-(4-amino-1H-indol-1-yl)piperidine-1-carboxylate

[00707] tert-butyl 4-(4-nitro-1H-indol-1-yl)piperidine-1-carboxylate (7 x 140.0 g, 405 mmol) was added to 7 separate solutions of Pd / C (20.0 g, 10% purity) in MeOH:THF (1:1, 1.0 L). The solutions were degassed with nitrogen and stirred for 12 h under a hydrogen atmosphere (30 PSI). The 7 batches were combined by Pd / C filtration and solvent evaporation. The resulting solid was used without further purification to yield the title compound (770.0 g, 86%) as a brown solid. 1H NMR δ 1.43 (s, 9H), 1.86-1.98 (m, 4H), 3.46-3.82 (m, 2H), 4.12 (d, J = 10.4 Hz, 2H), 4.59 (t, J = 3.6 Hz, 1H), 5.36 (s, 2H), 6.34 (d, J = 3.2 Hz, 1H), 6.89 (d, J = 7.2 Hz, 1H), 7.16 (t, J = 7.6 Hz, 1H), 7.56 (t, J = 3.6 Hz, 1H). Intermediate 5c: tert-butyl 4-{4-[(3-methoxy-3-oxopropyl)amino]-1H-indol-1-yl}piperidine-1-carboxylate Petition 870250080967, dated 09 / 09 / 2025, p. 174 / 523 165 / 482

[00708] tert-Butyl 4-(4-amino-1H-indol-1-yl)piperidine-1-carboxylate (5 x 175.0 g, 555 mmol) was added to 5 separate portions of MeOH (1.2 L). AcOH (5 x 499.0 g, 8.32 mol, 476 mL) was added to each mixture followed by methyl acrylate (471.0 g, 5.47 mol, 4923 mL) and stirred at 80 °C for 18 h. The batches were combined and the solvent was evaporated to produce the crude product which was extracted with EtOAc (10.0 L) and washed with NaHCO3 (15.0 L). The aqueous layer was extracted again with EtOAc (5.0 L x 3). The combined organics were washed with NaCl solution and dried with Na2SO4. The solvent was evaporated to yield the title compound (1.08 kg, crude) as a black oil and was used without further purification.1H-NMR 2H), 4.02-4.09 (m, 2H), 4.114.41 (m, 1H), 6.10 (d, 7.2 Hz, 1H), 6.39-6.54 (m, 1H), 6.78 (d, J = 8.4 Hz, 1H), 6.77-6.89 (m, 1H), 7.23 (s, 1H), 11.89 (s, 1H). Intermediate 5d: ter-butyl 4-{4-[carbamoyl(3-methoxy-3-oxopropyl)amino]-1H-indol-1-yl}piperidine-1carboxylate

[00709] 4-{4-[(3-methoxy-3-oxopropyl)amino]-1H-indol-1-yl}piperidine-1-carboxylate tert-butyl (6 x 200 g, 498 mmol) were added to DCM (6 x 1.0 l). AcOH (6 x 2.1 kg, 34.97 mol, 2.0 l) in DCM (6 x 1.0 l) was added to the mixture followed by potassium cyanate (6 x 40.4 g, 498 mmol) and stirred under TA for 2 h. The 6 batches were combined and water (5.0 l) was added to the mixture. DCM (8 l x 2) was added to the extraction which was washed with NaCl solution. The organic layer was dried with Na2SO4 and evaporated. The residue was Petition 870250080967, dated 09 / 09 / 2025, p. 175 / 523 166 / 482 purified by column chromatography, Et2O:EtOAc gradient elution 30:1 to 1:1 to yield the title compound (260.0 g, 19.6%) as a brown solid. 1H NMR δ 1.82 (s, 9H), 1.93-1.98 (m, 4H), 2.44-2.50 (m, 2H), 2.98 (s, 2H), 3.46 (s, 3H), 3.84 (s, 2H), 4.66 (d, J = 8.4 Hz, 2H), 4.66-4.78 (m, 1H), 5.36 (s, 2H), 6.34 (d, J = 3.2 Hz, 1H), 6.90 (d, J = 7.6 Hz, 1H), 7.16 (t, J = 8.4 Hz, 1H), 7.56 (t, J = 4 Hz, 2H). Intermediate 5e: ter-butyl 4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1H-indol-1-yl]piperidine-1-carboxylate

[00710] 4-{4-[carbamoyl(3-methoxy-3-oxopropyl)amino]-1H-indol-1-yl}piperidine-1-carboxylate tert-butyl (3 x 105.0 g, 236 mmol) in MeOH (3 x 779.0 g, 24.3 mol, 3 x 984 ml) were added to 3 separate vessels of MeOH (1.0 l) followed by MeONa / MeOH (42.5 g, 236 mmol, 30% purity). The reaction was stirred at room temperature for 2 hours and the combined solids were collected by filtration. The filtrate was evaporated and purified by column chromatography, DCM:MeOH 10:1 gradient elution to yield the title compound (180 g, 70.7%) as a white solid. 1H-NMR 4.59-4.60 (m, 1H), 6.41 (d, J = 3.2 Hz, 1H), 6.96 (d, J = 7.6 Hz, 1H), 7.15 (t, J = 7.6 Hz, 1H), 7.52-7.54 (m, 2H), 10.3 (s, 1H). Intermediate 5f: 1-[1-(piperidin-4-yl)-1H-indol-4-yl]-1,3-diazinane-2,4-dione tosylate Petition 870250080967, dated 09 / 09 / 2025, p. 176 / 523 167 / 482

[00711] 4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1H-indol-1-yl]piperidine-1-carboxylate tert-butyl (140.0 g, 339.41 mmol) in a MeCN solution (300 ml) was added to p-toluenesulfonic acid hydrate (82.6 g, 434 mmol) in MeCN (560 ml) by dropwise at room temperature. The reaction was stirred at 60 °C for 1 h. p-Toluenesulfonic acid hydrate (6.46 g, 33.9 mmol) was added to the mixture and stirred at 60 °C for a further 1 h. The reaction was then filtered and dried under vacuum to yield the title compound (120.0 g, 70.8%) as a gray solid. 1H NMR δ 2.06-2.16 (m, 4H), 2.29 (s,3H), 2.76 (t, J = 6.8 Hz, 2H), 3.19-3.45 (m, 2H), 3.45-3.48 (m, 3H), 3.77 (t, J = 6.4 Hz, 2H), 4,424.79 (m, 1H), 6.46 (d, J = 3.2 Hz, 1H), 6.99 (d, J = 7.6 Hz, 1H), 7.10 (d, J = 44.0 Hz, 2H), 7.14 (t, J = 14.0 Hz, 1H), 7.40 (d, J = 3.6 Hz, 1H), 7.52 (d, J = 8.0 Hz, 1 H), 7.56 (d, J = 8.4 Hz, 2H), 8.41 (d, J = 10.0 Hz, 1H), 8.68 (d, J = 10.0 Hz, 1 H), 10.3 (s, 1H); m / z: ES+ [M+H]+ = 313.1. Example 5: 4-chloro-7-(4{4-J4-({4-J4-(24-dioxo-13-diazinan-1-yl)-1H-indol]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-1H-indol-3carbonitrile

[00712] A suspension of intermediate 1 g (2.79 g, 6.24 mmol) and 1[1-(piperidin-4-yl)-1H-indol-4-yl]-1,3-diazinane-2,4-dione TsOH (intermediate 5f) (3.18 g, 6.55 mmol) in MPN (27.0 ml) was stirred at room temperature for 2.5 h. Sodium triacetoxyborohydride (1.58 g, 7.49 mmol) was added. Petition 870250080967, dated 09 / 09 / 2025, p. 177 / 523 168 / 482 and the solution continued to be stirred at room temperature for 1 h. The reaction mixture was rapidly cooled with water (100 ml) and the suspension was stirred at room temperature for 30 min. The solid was collected by filtration, washed with water (100 ml) and extracted in DCM:IPA (3:1, 500 ml). The organics were washed with NaHCO3 solution (150 ml) and NaCl solution (100 ml), dried with a phase separation cartridge and the solvent was evaporated to dryness. The crude product was purified by flash chromatography on silica, gradient elution of 50 to 100% EtOAc in heptane followed by 100% EtOAc for 15 min, 0 to 10% MeOH in DCM for 25 min and 10% MeOH in DCM for 20 min to yield the product as a solid. The product was suspended in MeCN (100 ml) at 80 °C for 1 h, then stirred at room temperature for 18 h. The solid was collected by filtration, washed with MeCN, and dried under vacuum at 50 °C to yield the title compound (2.52 g, 54.3%) as a dirty white solid.1H NMR δ 1.15 - 1.32 (3H, m), 1.61 - 1.74 (1H, m), 1.79 - 1.9 (4H, m), 1.89 - 2.04 (6H, m), 2.13 - 2.22 (2H, m), 2.26 (2H, d), 2.51 - 2.53 (1H, m) (1H, d), 6.88 - 6.95 (2H, m), 6.96 (1H, d), 7.09 - 7.2 (4H, m), 7.51 (1H, d), 7.54 (1H, d), 8.31 (1H, s), 10.31 (1H, s), 12.26 (1H, s); m / z: ES+[M+H]+= 743.4. Example 6:. 7-(4-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1H-indol-1-yl]piperidin-1yl}methyl)Γpiperidm-L·yl]phenyl}pperidin-L·yl)-4-fluoro-1H-i^^

[00713] A suspension of intermediate 2d (2.34 g, 5.44 mmol) and intermediate 5f (2.77 g, 5.71 mmol) in MPN (23.0 ml) was stirred at room temperature for 2.5 h. Sodium triacetoxyborohydride (1.38 g, 6.52 mmol) was added and the solution continued to be stirred at room temperature for 1 h. The reaction mixture was Petition 870250080967, dated 09 / 09 / 2025, p. 178 / 523 169 / 482 was rapidly cooled with water (100 ml) and the suspension was stirred at room temperature for 30 min. The solid was collected by filtration and washed with water. The solid was suspended in MeCN (50 ml) at 80 °C for 1 h, then allowed to cool at room temperature for 18 h. The suspension was vacuum filtered and washed with MeCN to produce the crude product. The crude product was purified by flash chromatography on silica, gradient elution of 50 to 100% EtOAc in heptane for 15 min, followed by 100% EtOAc for 15 min, 0 to 10% MeOH in DCM for 25 min, and 10% MeOH in DCM for 20 min to produce the product as a solid. The product was suspended in MeCN (100 ml) at 80 °C for 1 h, then stirred at room temperature for 18 h. The solid was collected by filtration, washed with MeCN, and dried under vacuum at 50 °C to yield the title compound (2.22 g, 56.2%) as a dirty white solid.1H NMR δ 1.18 - 1.3 (2H, m), 1.6 - 1.73 (1H, m), 1.84 (4H, d), 1.9 - 2.06 (6H, m), 2.13 - 2.23 (2H, m), 2.26 (2H, d), 2.55 - 2.58 (1H, m), 2.58 - 2.68 (2H, m), 2.71 2.82 (4H, m), 3.01 (2H, d), 3.38 (2H, d), 3.65 (2H, d), 3.78 (2H, t), 4.3 - 4.46 (1H, m), 6.42 (1H, d), 6.82 (1H, dd), 6.86 - 7.04 (4H, m), 7.14 (3H, t), 7.44 7.6 (2H, m), 8.26 (1H, s), 10.31 (1H, s), 12.24 (1H, s); m / z: ES+[M+H]+= 727.5. Example 7 Intermediate 7a: Methyl 4-bromo-2-methoxy-6-methylbenzoate

[00714] A 25% methanolic solution of sodium methanolate (512 µl, 2.24 mmol) was added dropwise to a stirred solution of methyl 4-bromo-2-fluoro-6-methylbenzoate (527 mg, 2.13 mmol) in DMF (10 ml) at room temperature under nitrogen. The resulting mixture was stirred at room temperature for 18 h. The reaction mixture was cooled to 0 °C and then briskly cooled with EtOAc (20 ml) and HCl (1 M, 10 ml). The phases were separated, and the aqueous phase was Petition 870250080967, dated 09 / 09 / 2025, page 179 / 523 170 / 482 extracted with EtOAc (2 x 30 ml). The organic phases were combined, dried with MgSO4, filtered and evaporated to produce the crude product. The crude product was purified by flash chromatography on silica, gradient elution of EtOAc from 0 to 25% in heptane to yield the title compound (0.410 g, 74%) as a colorless oil that solidified on stand; 1H NMR (CDCb) δ 2.25 (3H, s), 3.81 (3H, s), 3.90 (3H, s), 6.91 (1H, d), 6.98 (1H, dd); m / z: ES+ [M+H]+ = 227.3. Intermediate 7b: 3-(5-bromo-7-methoxy-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6dione

[00715] NBS (1.57 g, 8.84 mmol) was added to a stirred solution of methyl 4-bromo-2-methoxy-6-methylbenzoate (1.43 g, 5.53 mmol) and AIBN (0.182 g, 1.11 mmol) in t-butyl acetate (20 ml). The reaction was stirred at 100 °C for 3 h. The reaction was cooled to room temperature, diluted with EtOAc (50 ml) and washed with water (50 ml). The organic layer was passed through a phase separation cartridge and concentrated. The crude product was purified by flash chromatography on silica, gradient elution of 0 to 15% EtOAc in heptane to yield 4-bromo-2-(bromomethyl)-6-methoxybenzoate (1.49 g, 80%) as a yellow gum, which was 70% pure. The solid was added to MeCN (20 ml) followed by DIPEA (1.65 ml, 9.29 mmol) and 3-aminopiperidine-2,6-dione hydrochloride (0.510 g, 3.10 mmol) to TA. The resulting solution was stirred at 80 °C for 16 h. The reaction mixture was cooled to 0 °C and the solid was collected by filtration.The solid was washed with MeCN (50 ml) and Et2O (50 ml) and dried under vacuum to yield the title compound (0.761 g, 39% in 2 steps) as a mauve solid. 1H NMR δ 1.97 (1H, dtd), 2.34 (1H, qd), 2.54 - 2.63 (1H, m), 2.90 (1H, m), 3.90 (3H, s), 4.25 (1H, d), 4.38 (1H, d), 5.02 (1H, dd), 7.26 (1H, d), 7.39 (1H, d), 10.94 (1H, s); m / z: ES+ [M+H]+ = 353.0. Petition 870250080967, dated 09 / 09 / 2025, p. 180 / 523 171 / 482 Intermediate 7c: tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo-2,3-dihydro-1H-isoindol-5yl]piperazine-1-carboxylate

[00716] Pd-PEPPSI-IHeptCl (0.380 g, 0.39 mmol) was added to tert-butyl piperazine-1-carboxylate (2.18 g, 11.72 mmol), CS2CO3 (3.82 g, 11.72 mmol) and 3-(5-bromo-7-methoxy-1-oxo-1,3-dihydro-2H-isoindol-2yl)piperidine-2,6-dione (1.38 g, 3.91 mmol) in degassed 1,4-dioxane (39 ml) at room temperature under nitrogen. The resulting suspension was stirred at 100 °C for 6 h. The reaction mixture was diluted with DCM (100 ml) and washed sequentially with 5% AcOH in water (100 ml), water (100 ml), NaHCO3 solution (100 ml), and NaCl solution (100 ml). The organic layer was dried with MgSO4, filtered, and evaporated to yield the crude product. The crude product was ground with EtOAc (40 ml) and washed with Et2O (50 ml) to yield a solid which was collected by filtration and vacuum dried to yield the title compound (1.15 g, 64%) as a dark gray solid.RMN de 1H δ 1.43 (9H, s), 1.79 - 1.97 (1H, m), 2.28 (1H, dd), 2.53 - 2.62 (1H, m), 2.76 - 2.94 (1H, m), 3.32 (4H, s), 3.41 - 3.54 (4H, m), 3.85 (3H, s), 4.12 (1H, d), 4.24 (1H, d), 4.95 (1H, dd), 6.51 (1H, d), 6.62 (1H, s), 10.87 (1H, s); m / z: ES+[M+H]+= 459,2. Example 7: 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-il)-7-metoxi-1-oxo-2,3-dihidro-1 H-isoindol-5-il]piperazin-1-il} metil)piperidin-1-il]fenil}piperidin-1il)-1 H-indol-3 -carbonitrila Petition: 870250080967, on September 9, 2025, page. 181 / 523 172 / 482

[00717] Intermediate 1f (780 mg, 1.59 mmol) and tert-butyl 4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo-2,3-dihydro-1H-isoindol-5-yl]piperazine1-carboxylate (874 mg, 1.91 mmol) were heated in formic acid (5 ml, 132.54 mmol) at 60 °C for 2 h. The reaction mixture was concentrated and the crude residue was suspended in MPN (5 ml) at room temperature, stirred for 5 minutes, and sodium triacetoxyborohydride (673 mg, 3.18 mmol) was added. The resulting suspension was stirred at room temperature for 10 min. The reaction mixture was poured into NaHCO3 solution (20 ml) and the resulting solid was collected by filtration, washed with MeCN (20 ml) and EtOAc (20 ml). The solid was purified by preparative HPLC (Column A, Eluent A). The fractions containing the product were evaporated and dissolved in DCM (250 ml), washed with NaHCO3 solution (100 ml) and NaCl solution (100 ml). The organic layer was dried with MgSO4 and evaporated to dryness to yield the title compound (350 mg, 27.9%) as a white solid.1H NMR δ 1.19 - 1.3 (2H, m), 1.70 (1H, s), 1.79 - 1.88 (4H, m), 1.9 - 2.03 (3H, m), 2.24 (2H, d), 2.31 (1H, d), 2.53 (4H, d), 2.60 (4H, dd), 2.79 (2H, t), 2.85 - 2.97 (1H, m), 3.43 (2H, d), 3.65 (2H, d), 3.84 (3H, s), 4.11 (1H, d), 4.24 (1H, d), 4.97 (1H, dd), 6.50 (1H, s), 6.62 (1H, s), 6.89 (3H, dd), 7.16 (3H, dd), 8.32 (1H, s), 10.90 (1H, s), 12.26 (1H, s); m / z: ES+[M+H]+= 790.0. Example 8 Intermediate 8a: 7-bromo-4-methyl-1H-indole-3-carbonitrile

[00718] Chlorosulfonyl isocyanate (1.9 ml, 22.61 mmol) was added dropwise to a cooled solution of 7-bromo-4-methyl-1-hindol (5.0 g, 23.8 mmol) in MeCN (94 ml) and DMF (23 ml) at 0 °C. The reaction was stirred at room temperature for 1.5 h. The reaction was then rapidly cooled with NaHCO3 solution (50 ml) and diluted with DCM (100 ml). The organic layer Petition 870250080967, dated 09 / 09 / 2025, p. 182 / 523 173 / 482 was dried with a phase separation cartridge and the solvent evaporated to produce the crude product which was purified by column chromatography, gradient elution of EtOAc from 0 to 30% in heptane to yield the title compound (3.93 g, 70.2%) as a creamy solid. 1H NMR (CDCf) δ 2.75 (3H, d), 6.92 (1H, m), 7.35 (1H, m), 7.78 (1H, m), 8.73 (1H, s); m / z: ES+ [M+H]+ = 235.0. Intermediate 8b: 7-(4-{4-[4-(1,3-dioxolan-2-yl)piperidin-1-yl]phenyl}piperidin-1-yl)-4-methyl-1 Hindol-3-carbonitrile

[00719] To a mixture of 7-bromo-4-methyl-1H-indol-3-carbonitrile (459 mg, 1.95 mmol), intermediate 1e (1.23 g, 3.90 mmol), RuPhos (27.3 mg, 0.06 mmol) and RuPhos Pd G3 (49.0 mg, 0.06 mmol) in 1,4-dioxane (3 ml) under nitrogen, LHMDS (1 M in THF, 10.63 ml, 10.63 mmol) was added and the reaction was stirred at 90 °C for 1 h. The reaction mixture was cooled to room temperature, diluted with EtOAc (50 ml), washed with water (2 x 50 ml) and NaCl solution (25 ml). The organic layer was dried with a phase separation cartridge and evaporated to yield the crude product. The crude product was purified by flash chromatography on silica, gradient elution of EtOAc from 0 to 100% in heptane to yield the title compound (0.388 g, 42.2%) as a yellow solid.RMN de 1H δ 1.37 - 1.48 (3H, m), 1.57 - 1.7 (3H, m), 1.7 - 1.79 (3H, m), 2.57 - 2.63 (4H, m), 2.69 - 2.79 (2H, m), 3.38 (2H, d), 3.68 (2H, d), 3.74 - 3.95 (6H, m), 4.58 - 4.66 (1H, m), 6.78 (1H, d), 6.91 (3H, d), 7.14 (2H, d), 8.12 - 8.21 (1H, m), 11.90 (1H, s); m / z: ES+ [M+H]+ = 471,4. Example 8:. 7-(4-{4-f4-£{4-f4-(2J4-dioxo-1,3-diazinan-1-il)-1H-indol-1-il]piperidin-1il}metil)piperidin-1-il]fenil}piperidin-1 -il)-4-metil-1H-indol-3-carbonitrila Petition: 870250080967, on September 9, 2025, page. 183 / 523 174 / 482

[00720] 7-(4-{4-[4-(1,3-dioxolan-2-yl)piperidin-1-yl]phenyl}piperidin-1yl)-4-methyl-1H-indol-3-carbonitrile (424 mg, 0.76 mmol) was heated in formic acid (5 ml, 129.46 mmol) at 40 °C for 2.5 h. The reaction mixture was concentrated and the crude residue was suspended in MPN (2 ml) at room temperature. Intermediate 5f (528 mg, 1.14 mmol) was added and the reaction mixture was stirred at room temperature for 5 min. Sodium triacetoxyborohydride (565 mg, 2.67 mmol) was added and the resulting suspension continued to be stirred at room temperature for 10 min. The reaction mixture was rapidly cooled with water (10 ml) and the product was extracted with DCM:IPA (9:1, 25 ml). The organic layer was washed with NaHCO3 solution, NaCl solution (10 ml) and dried with a phase separation cartridge. The solvent was evaporated and the crude product was purified by flash chromatography on silica, gradient elution of IPA from 0 to 25% in DCM to yield the title compound (291 mg, 0.403 mmol, 52.9%) as a white solid.RMN de 1H δ 1,16 - 1,31 (3H, m), 1,61 - 1,75 (1H, m), 1,84 (4H, d), 1,89 - 2,09 (6H, m), 2,13 - 2,31 (4H, m), 2,55 - 2,61 (4H, m), 2,61 2,7 (1H, m), 2,7 - 2,82 (4H, m), 3,02 (2H, d), 3,38 (2H, d), 3,65 (2H, d), 3,72 - 3,83 (2H, m), 4,39 (1H, s), 6,42 (1H, d), 6,77 (1H, d), 6,84 - 6,94 (3H, m), 6,96 (1H, dd), 7,11 - 7,18 (3H, m), 7,51 (1H, d), 7,54 (1H, d), 8,16 (1H, d), 10,31 (1H, s), 11,89 (1H, s); m / z: ES+[M+H]+= 723,5. Exemplo 9 Intermediário 9a: 7-bromo-4-cloro-1 H-indazol Petição 870250080967, de 09 / 09 / 2025, pág. 184 / 523 175 / 482

[00721] 3-bromo-6-chloro-2-fluorobenzaldehyde (23.0 g, 96.86 mmol) was added to 1,2-dimethoxyethane (230 ml) and hydrazine hydrate (14.55 g, 290.58 mmol) was added. The mixture was stirred under reflux for 36 h, cooled to room temperature, and then poured into rapidly stirred water (460 ml) for 30 min. The resulting solid was filtered and washed with water (2 x 200 ml) and dried in a vacuum oven at 50 °C for 24 h to yield the title compound (21.80 g, 97%) as a white solid. 1H NMR δ 7.16 (1H, d), 7.60 (1H, d), 8.30 (1H, s), 13.02 (1H, s); m / z: ES+ [M+H]+ = 231.1. Intermediate 9b: 7-bromo-4-chloro-3-iodo-1 H-indazole

[00722] 7-bromo-4-chloro-1H-indazole (21.0 g, 90.72 mmol) was added to DMF (100 ml) and potassium hydroxide (20.36 g, 362.89 mmol) and cooled to 0 °C. Iodine (29.9 g, 117.94 mmol) was added and after 5 min the reaction was stirred at room temperature for 30 min. The reaction was rapidly cooled with sodium thiosulfate (20% aq, 250 ml) and extracted with EtOAc (250 ml). The organic layer was washed with lithium chloride (10% aq, 250 ml), water (2 x 250 ml), NaCl solution (100 ml), dried with a phase separation cartridge and the solvent evaporated to yield the title compound (31.2 g, 96%) as a creamy solid. 1H NMR δ 7.15 (1H, d), 7.63 (1H, d), 14.23 (1H, s); m / z: ES- [MH]-= 355.0. Intermediate 9c: 7-bromo-4-chloro-1 H-indazol-3-carbonitrile _ Petition 870250080967, dated 09 / 09 / 2025, page 185 / 523 176 / 482

[00723] 7-bromo-4-chloro-3-iodo-1H-indazole (10.0 g, 27.98 mmol) and potassium(II) hexacyanoferrate trihydrate (4.73 g, 11.19 mmol) were added to dimethylacetamide (80 ml) under nitrogen and stirred at 60 °C for 10 min. Water (60 ml) was added followed by Xantphos (0.810 g, 1.40 mmol) and allylpalladium(II) chloride dimer (0.256 g, 0.70 mmol) and the mixture was stirred at 95 °C for 4.5 h. The reaction was cooled to room temperature, filtered through Celite® and washed with 2-MeTHF (200 ml). The mother liquor was diluted with water (200 ml) and washed with water (2 x 200 ml), NaCl solution (100 ml), dried with a phase separation cartridge, and the solvent was evaporated. The crude product was suspended in MeCN (50 ml) and stirred under reflux. Water (50 ml) was added followed by MeCN (20 ml). The solution was decanted hot through cotton and allowed to cool to room temperature. The resulting solid was filtered, vacuum dried, and made into an aqueous paste in DCM (20 ml) for 5 min.The resulting solid was vacuum dried to yield the title compound (4.55 g, 63.4%) as a dirty white solid. 1H NMR δ 7.40 (1H, d), 7.79 (1H, d), 15.17 (1H, s); m / z: ES [MH] = 254.0. Intermediate 9d: (3S)-32(4-bromophenyl)pipeidine212benzylcarboxylate

[00724] K2CO3 (2 M, 159.0 ml, 318.01 mmol) was added in portions to a solution of (S)-3-(4-bromophenyl)piperidine oxalate (35.0 g, 106.00 mmol) in THF (250 ml) and water (100 ml) at room temperature. 1{[(benzyloxy)carbonyl]oxy}pyrrolidine-2,5-dione (26.4 g, 106.00 mmol) was then added in portions and stirred at room temperature for 18 h. The mixture was diluted with EtOAc (500 ml) and water (250 ml), stirred for 10 min, and the layers separated. The organic layer was washed with citric acid (1 M, 250 ml), NaCl solution (200 ml), dried with a phase separation cartridge, and Petition 870250080967, dated 09 / 09 / 2025, p. 186 / 523 1ΊΊ / 482 evaporated to dryness to produce the crude product. The crude product was dissolved in EtOH (100 ml) and water (300 ml), stirred at 60 °C and then cooled to room temperature. The resulting solid was vacuum filtered and dried in a vacuum oven at 45 °C to yield the title compound (3Ί.6 g, 94%) as a creamy solid. 1H NMR δ 1.48 (1H, m), 1.63 (1H, m), 1.Ί2 (1H, m), 1.83 - 1.93 (1H, m), 2.65 (1H, tt), 2.8Ί (2H, s), 3.96 - 4.08 (2H, m), 5.10 (2H, s), Ί.24 ​​(2H, d), Ί.28 - Ί.42 (5H, m), Ί.50 (2H, d); m / z: ES+[M+H]+= 3Ί4.1. Intermediate 9e: (3S)Σ3-{4=[4Σ(XJJ:dioχΌlanΣ2Σil)piperidin=l·:il]jenyl}^^ benzyl [00Ί25] 4-(1,3-dioxolan-2-yl)piperidine (25.9 g, 164.Ί4 mmol), (3S)-3(4-bromophenyl)piperidine-1-benzyl carboxylate (56.1 g, 149.ΊΊ mmol) and Cs2CO3 (98.0 g, 299.54 mmol) were degassed with nitrogen in 1,4-dioxane (500 ml) for 10 min. Pd(t-Bu3P)2 (3.83 g, Ί,49 mmol) and tri-tert-butylphosphonium tetrafluoroborate (4.35 g, 14.98 mmol) were then added and the mixture stirred at 100 °C for 20 h. The reaction mixture was cooled to room temperature and the solid was filtered through Celite®. The solid was washed with 1,4-dioxane (200 ml) and the filtrate was evaporated to produce the crude product. The crude product was purified by flash chromatography on silica, gradient elution of 10 to 50% EtOAc in heptane to yield the title compound (28.5 g, 42.2%) as a creamy solid.RMN de1H δ 1.33 - 1.52 (3H, m), 1.55 - 1.68 (2H, m), 1.68 - 1.Ί8 (3H, m), 1.85 (1H, d), 2.54 (1H, s), 2.59 (2H, td), 2.84 (2H, s), 3.6Ί (2H, d), 3.Ί4 - 3.83 (2H, m), 3.83 - 3.92 (2H, m), 3.94 - 4.09 (2H, m), 4.61 (1H, d), 5.09 (2H, s), 6.8Ί (2H, d), Ί.08 (2H, d), Ί.2Ί - Ί.45 (5H, m); m / z: ES+[M+H]+= 451,3. Petition: 870250080967, on September 9, 2025, page. 187 / 523 178 / 482 Intermediário 9f: 4^132^0^018^22211)21^41(381=21^611^^23206^111.^1^6^

[00726] (3 5)-3-{4-[4-(1,3-dioxo1an-2-i1)piperidin-1-i1]pheni1}piperidine1-carboxy1ate benzyl (27.5 g, 61.03 mmol) was suspended in EtOH (100 ml) and DCM (20 ml). Pd / C (10%, 2.6 g, 2.44 mmol) was added and the reaction was hydrogenated at TA with a pressure of 2 bar for 16 h. DCM (50 ml) was added to the reaction mixture and filtered through Celite®. The filtrate was evaporated to dryness and stirred in MTBE (50 ml) for 16 h, filtered and dried under vacuum to yield the title compound (14.95 g, 77%) as a creamy solid. 1H NMR δ 1.33 - 1.44 (2H, m), 1.48 (2H, d), 1.62 (2H, m), 1.72 (2H, d), 1.82 (1H, d), 2.47 (4H, d), 2.58 (2H, m), 2.94 (2H, d), 3.65 (2H, d), 3.75 - 3.83 (2H, m), 3.83 - 3.9 (2H, m), 4.61 (1H, d), 6.84 (2H, d), 7.04 (2H, d); m / z: ES+[M+H]+= 317.2. Intermediate 9g: 4-chloro-7-[(3S)-3-{4-[4-(1,3 dioxolan~2 -i1)piperidin-1 -i1]pheni1}piperidin-1 ·ϊ1]· 1H-indazo1-3-carbonitri1a

[00727] The intermediate 9c (2.3 g, 8.98 mmol) and 4-(1,3-dioxo1an-2-i1)1·{4·[(3 S)-piperidin-3-i1]pheni1}piperidine (2.90 g, 9.16 mmol) were suspended in 2MeTHF (25 ml). The mixture was degassed with nitrogen for 10 min followed by the addition of CPhos (0.39 g, 0.90 mmol) and [Pd(cinnamyl)Cl]2 Petition 870250080967, dated 09 / 09 / 2025, p. 188 / 523 179 / 482 (0.23 g, 0.45 mmol). LHMDS (1 M in THF, 31.4 mL, 31.45 mmol) was added and the reaction was stirred at 50 °C for 1 h. The reaction was then cooled to room temperature and partitioned between water (25 mL) and 2-MeTHF (25 mL). The organic layer was washed with NaCl solution (25.0 mL), dried through a phase separation cartridge, and the solvent was evaporated to yield the crude product. The crude product was purified by flash chromatography on silica, gradient elution of EtOAc from 0 to 100% in heptane to yield the title compound (2.46 g, 55.6%) as a pale orange solid. 1H-NMR d); m / z: ES+[M+H]+= 492.3. Intermediate 9am: 4-chloro-7-{(3S)-3-[4-(4-formylpiperidin-1-yl)phenyl]piperidin-1-yl}-1H-indazol3-carbonitrile

[00728] To a stirred solution of 4-chloro-7-[(3S)-3-{4-[4-(1,3dioxolan-2-yl)piperidin-1-yl]phenyl}piperidin-1-yl]-1H-indazol-3-carbonitrile (3.15 g, 6.40 mmol) in THF (32.0 ml) was added HCl (2 M, 64.0 ml, 128.04 mmol). The reaction mixture was stirred at 60 °C for 4 h, then cooled to 0 °C in an ice bath. The mixture was neutralized to pH 7 with NaOH (2 M), extracted with 2-MeTHF (100 ml), washed with water (100 ml), NaCl solution (50 ml), dried with a phase separation cartridge, and the solvent was evaporated to yield the crude product. The crude product was purified by flash chromatography on silica, gradient elution of EtOAc to Petition 870250080967, dated 09 / 09 / 2025, page 189 / 523 180 / 482 a 100% heptano to render the composition do the tulo (2.5 g, 87%) combined with a solid amarelo. RMN de 1H δ 1.58 (3H, m), 1.83 - 1.98 (5H, m), 2.46 (1H, m), 2.66 - 2.82 (4H, m), 2.94 - 3.06 (1H, m), 3.4 - 3.6 (4H, m), 6.89 (2H, d), 6.93 (1H, d), 7,18 (2H, d), 7,27 (1H, d), 9,63 (1H, d), 14,69 (1H, s); m / z: ES+[M+H]+= 448,3. Example 9: 4-chloro-7-[(3S)-3-{4-[4-({4-[4-(2,4-dioxo- 1,3-diazinan-1 -il)-1 H-indol-1 il]piperidin-T-il}metil)piperidin-1j-il]Onil}pperidin-^^ carbonitrila

[00729] A suspension of 4-chloro-7-{(3S)-3-[4-(4-formylpiperidin-1yl)phenyl]piperidin-1-yl}-1H-indazol-3-carbonitrile (9.22 g, 20.58 mmol) and intermediate 5f (10.47 g, 21.61 mmol) in MPN (92 ml) was stirred at room temperature for 18 h. Sodium triacetoxyborohydride (5.23 g, 24.70 mmol) was added and the solution continued to be stirred at room temperature for 2 h. The reaction mixture was rapidly cooled with water (250 ml) and the suspension was stirred at room temperature for 30 min. The solid was collected by filtration, washed with excess water, and extracted with DCM:IPA (3:1, 250 ml). The organic layer was washed with NaHCO3 solution (100 ml), NaCl solution (100 ml) and dried with a phase separation cartridge. The solvent was evaporated and the crude product was purified by flash chromatography on silica, gradient elution of EtOAc from 0 to 100% in heptane followed by MeOH from 0 to 10% in EtOAc. The product was then suspended in MeCN (225 ml) at 80 °C for 3 h, then allowed to cool to room temperature for 16 h.The solid was collected by filtration, washed with excess MeCN, and dried under vacuum at 45 °C to yield the title compound (11.57 g). Petition 870250080967, dated 09 / 09 / 2025, p. 190 / 523 181 / 482 %) as a pale orange solid. 1H NMR δ 1.17 - 1.29 (2H, m), 1.53 - 1.72 (2H, m), 1.79 - 1.85 (2H, m), 1.85 - 1.99 (5H, m), 1.98 - 2.06 (2H, m), 2.15 - 2.24 (2H, m), 2.27 (2H, d), 2.57 - 2.65 (2H, m), 2.66 - 2.79 (4H, m), 2.95 - 3.05 (3H, m), 3.43 - 3.55 (2H, m), 3.63 (2H, d), 3.78 (2H, t), 4.33 - 4.43 (1H, m), 6.41 (1H, d), 6.88 (2H, d), 6.92 (1H, d), 6.96 (1H, d), 7.12 - 7.2 (3H, m), 7.26 (1H, d), 7.51 (1H, d), 7.53 (1H, d), 10.31 (1H, s), 14.55 (1H, s); m / z: ES+[M+H]+= 744.4. Example 10: 4-chloro-7-[(3S)-314-[4H42l2(26-dioxopperidin-3yl)-1 1H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1-yl]phenyl}p iperidin-1-yl]-1 Hindazol-3-carbonitrile

[00730] Intermediate 9g (2.0 g, 3.46 mmol) and intermediate 1i (1.48 g, 3.46 mmol) were heated in formic acid (20 ml) at 40 °C for 2 h. The reaction mixture was cooled, evaporated to dryness, and the residue was stirred in MPN (20 ml) at TA for 16 h. The reaction mixture was poured into NaHCO3 solution (300 ml) and the precipitate was collected by filtration, washed with water (100 ml) and dried under vacuum to yield the crude product which was purified by flash chromatography on silica, gradient elution of DCM from 0 to 6% in EtOH. The pure fractions were evaporated to dryness to produce the product which was made into an aqueous paste in MeCN (50 ml) and vacuum filtered to yield the title compound (1.17 g, 44.5%) as a yellow solid. 1H NMR δ 1.12-1.27 (2H, m), 1.49-1.59 (1H, m), 1.59-1.71 (1H, m), 1.73-2.01 (6H, m), 2.19 (2H, d), 2.28-2.43 (1H, m), 2.49 (4H, dd), 2.54-2.78 (5H, m), 2.83-3.04 (2H, m), 3.27 (4H, t), 3.46 (2H, t), 3.60 (2H, d), Petition 870250080967, dated 09 / 09 / 2025, p. 191 / 523 182 / 482 4.16-4.37 (2H, m), 5.05 (1H, dd), 6.88 (3H, dd), 7.04 (2H, d), 7.15 (2H, d), 7.25 (1H, d), 7.52 (1H, d), 10.95 (1H, s), 14.62 (1H, s); m / z: ES+[M+H]+= 760.0. Example 11 Intermediate 11a: Benzyl (3S)-3-{4-[4-(dibutoxymethyl)piperidin-1-yl]phenyl}piperidine-1-carboxylate

[00731] Pd( t-Bu3P)2 (0.55 g, 1.07 mmol) was added to the intermediate 9d (4.0 g, 10.69 mmol), 4-(dibutoxymethyl)piperidine (2.6 g, 10.69 mmol), CS2CO3 (6.96 g, 21.37 mmol), and tri-tert-butylphosphonium tetrafluoroborate (0.310 g, 1.07 mmol) in 1,4-dioxane (50 ml) under nitrogen. The resulting mixture was stirred at 100 °C for 2 h. The mixture was then cooled to room temperature and the solvent evaporated to yield the crude product. The crude product was purified by flash chromatography on silica, gradient elution of 0 to 40% EtOAc in Et2O to yield the title compound (2.3 g, 40.1%) as a yellow oil. 1H NMR δ 0.89 (6H, t), 1.24-1.55 (12H, m), 1.57-1.91 (6H, m), 2.59 (1H, s), 2.82 (2H, s), 3.32-3.46 (3H, m), 3.49-3.71 (4H, m), 4.01 (2H, t), 4.19 (1H, d), 5.09 (2H, s), 6.86 (2H, d), 7.07 (2H, d), 7.35 (5H, q); m / z: (ES+), [M+H]+= 537.5. Intermediate 11b: 4Σ(dbutoxymethyl)ΣL·{4J:[(3S)Σpiperidin=3Π]fe Petition 870250080967, dated 09 / 09 / 2025, p. 192 / 523 183 / 482

[00732] Pd / C (10%, 0.912 g, 0.86 mmol) was added to (3S)-3-{4-[4(dibutoxymethyl)piperidin-1-yl]phenyl}piperidine-1-carboxylate benzyl (2.3 g, 4.28 mmol) in EtOAc:MeOH (5:1, 30 ml) at room temperature under a hydrogen atmosphere for 3 h. The mixture was filtered through Celite® and evaporated to dryness to yield the title compound (1.6 g, 93%) as a white oil which was used without further purification. 1H NMR δ 0.89 (6H, t), 1,241.42 (4H, m), 1.43-1.57 (5H, m), 1.59-1.87 (4H, m), 2.43 (4H, d), 2.57 (1H, s), 2.91 (2H, d), 3.22-3.47 (7H, m), 3.49-3.69 (4H, m), 4.19 (1H, d), 6.84 (2H, d), 7.04 (2H, d); m / z: (ES+), [M+H]+= 403.1. Intermediate 11c: 42chloro272[(3S)232J4J42(dibutoχimethyl)piperidin-L·yl]phenyl^^ indole-3-carbonitrile

[00733] ​​LHMDS (1 M in THF, 10.43 ml, 10.43 mmol) was added to 4-(dibutoxymethyl)-1-{4-[(35)-piperidin-3-yl]phenyl}piperidine (1.2 g, 2.98 mmol), intermediate 1b (0.838 g, 3.28 mmol), and Pd-PEPPSI-IHeptCl (0.145 g, 0.15 mmol) in THF (5.0 ml). The resulting mixture was stirred at 60 °C for 2 h. The reaction mixture was cooled to TA, then rapidly cooled. Petition 870250080967, dated 09 / 09 / 2025, p. 193 / 523 184 / 482 with NH4Cl solution (10 ml), extracted with EtOAc (2 x 20 ml), dried with Na2SÜ4, filtered and evaporated to produce the crude product. The crude product was purified by flash chromatography on silica, gradient elution of EtOAc from 0 to 30% in Et2Ü to yield the title compound (1.4 g, 81%) as a brown solid. 1H NMR δ 0.89 (6H, t), 1.27-1.4 (6H, m), 1.43-1.54 (5H, m), 1.72 (4H, d), 1.79-1.98 (3H, m), 2.53-2.8 (4H, m), 2.98 (1H, d), 3.36-3.43 (3H, m), 3.49-3.7 (4H, m), 4.18 (1H, d), 6.8-6.9 (3H, m), 7.09-7.2 (3H, m), 8.31 (1H, d), 12.28 (1H, d); m / z: (ES+), [M+H]+= 577.3. Example 11: 4-chloro-7-[(3S)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1H-indol-1yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl]-1H-indol-3carbonitrile

[00734] 4-chloro-7-[(3 5)-3-{4-[4-(dibutoxymethyl)piperidin-1-yl]phenyl}piperidin-1-yl]-1H-indol-3-carbonitrile (1.2 g, 2.08 mmol) was heated in formic acid (16.0 ml, 417.16 mmol) at 40 °C for 1 h. The mixture was cooled and evaporated and diluted in NMP (16.0 ml). Intermediate 5f (1.01 g, 2.08 mmol) and sodium acetate (0.205 g, 2.49 mmol) were added and the resulting mixture was stirred at 40 °C for 2 h. The reaction mixture was then poured into Na2CÜ3 solution (150 ml) and the precipitate was collected by filtration, washed with water (50 ml) and vacuum dried to produce the crude product. The crude product was purified by flash chromatography on silica, gradient elution of DCM from 0 to 10% in EtOH to produce the product which was transformed into an aqueous paste in MeCN (50 ml) and vacuum filtered to yield the title compound (1.16 g, 75%) as a white solid. NMR Petition 870250080967, dated 09 / 09 / 2025, page 194 / 523 185 / 482 of 1H δ 1.21 (2H, m), 1.46-1.72 (2H, m), 1.82 (3H, dd), 1.87-2.05 (6H, m), 2.17 (4H, dd), 2.63 (4H, dq), 2.7 (4H, dd), 2.63 (4.7), t 3.30 (1H, d), 3.36 (1H, s), 3.61 (2H, d), 3.77 (2H, t), 4.36 (1H, tt), 6.41 (1H, d), 6.84 (3H, dd), 6.96 (1H, d), 7.14 (4H, dd), (2.4-7) m 8.31 (1H, s), 10.34 (1H, s), 12.28 (1H, s); m / z; ES+[M+H]+= 743.3. Example 12: 4-chloro-7-[(3S)-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1-yl]phenyl}p hyperidin-1-hydro-hydro-carbon-3-la

[00735] Intermediate 11c (2.3 g, 3.98 mmol) and intermediate 1i (1.7 g, 3.98 mmol) were heated in formic acid (20 ml) at 40 °C for 1 h. The reaction was then cooled and evaporated to produce a residue which was diluted with NMP (20 ml). The resulting mixture was stirred at 40 °C for 16 h, then poured into Na2CO3 solution (300 ml). The precipitate was collected by filtration, washed with water (50 ml) and dried under vacuum to produce the crude product. The crude product was purified by flash chromatography on silica, gradient elution of DCM from 0 to 6% in EtOH to produce the product which was transformed into an aqueous paste in MeCN and filtered under vacuum to yield the title compound (0.93 g, 30.7%) as a white solid.1H NMR δ 1.14-1.28 (2H, m), 1.46-1.61 (1H, m), 1.68 (1H, d), 1.74-1.87 (3H, m), 1.882 (3H, m), 2.20 (2H, d), 2.28-2.44 (1H, m), 2.45-2.5 (3H, m), 2.51 (1H, s), 2.54-2.73 (5H, m), 2.83-3.03 (2H, m), 3.24-3.31 (4H, m), 3.35 (2H, d), 3.61 (2H, d), 4.21 (1H, d), 4.33 (1H, d), 5.05 (1H, dd), 6.84 (3H, dd), 7.05 (2H, d). Petition 870250080967, dated 09 / 09 / 2025, p. 195 / 523 186 / 482 7.14 (3H, dd), 7.52 (1H, d), 8.31 (1H, s), 10.94 (1H, s), 12.27 (1H, s); m / z: ES+[M+H]+= 759.5. Example 13 Intermediate 13a: tert-butyl 4-[(2-amino-4-bromophenyl)ethynyl]piperidine-1-carboxylate

[00736] PdCl2(PPh3)2 (3.36 g, 4.78 mmol) was added in a portion to tert-butyl 4-ethinylpiperidine-1-carboxylate (10.01 g, 47.83 mmol), 5-bromo-2-iodoaniline (14.25 g, 47.83 mmol), copper(I) iodide (1.36 g, 7.17 mmol), and triethylamine (19.97 ml, 143.49 mmol) in DMF (145 ml) at room temperature under nitrogen. The resulting dark brown solution was stirred at room temperature for 18 h. The reaction mixture was diluted with water (150 ml) and the product extracted in MTBE (150 ml). The organic layer was washed with water (150 ml), NaCl solution (50 ml), dried with MgSÜ4 and evaporated to produce the crude product. The crude product was purified by column chromatography, heptane:EtOAc gradient elution at 5 to 20% to yield the title compound (24.14 g, 55%) as an orange oil. 1H NMR δ 1.46 (9H, s), 1.68 (2H, m), 1.88 (2H, m), 2.83 (1H, m), 3.18 - 3.26 (2H, m), 3.76 (2H, m), 4.18 (2H, s), 6.78 (1H, m), 6.84 (1H, m), 7.08 (1H, m); m / z: ES+[M+H]+= 379.1. Intermediate 13b: tert-butyl 4-(6-bromo-1-methyl-1H-indol-2-yl)piperidine-1-carboxylate

[00737] Potassium tert-butoxide (13.30 g, 118.48 mmol) was added in portions to tert-butyl 4-[(2-amino-4-bromophenyl)ethynyl]piperidine-1-carboxylate (21.4 g, 39.49 mmol) in NMP (200 ml) and stirred under TA for 3 h. Petition 870250080967, dated 09 / 09 / 2025, p. 196 / 523 187 / 482 Iodomethane (7.38 ml, 118.48 mmol) was added in portions and stirred at room temperature for 1 h. The reaction mixture was then rapidly cooled with NH4Cl solution (100 ml) and water (100 ml). The product was extracted with 2MeTHF (2 x 200 ml) and the combined organic layers were washed with water (2 x 100 ml), NaCl solution (100 ml), dried with MgSO4, and evaporated to yield the crude product as a brown oil. The crude product was purified by flash chromatography on silica, gradient elution of EtOAc from 0 to 50% in heptane. The pure fractions were evaporated to yield a solid which was ground with heptane (50 ml). The solid was collected by filtration and dried in a vacuum oven at 45 °C to yield the title compound (13.74 g, 88%) as a white solid. 1H NMR δ 1.51 (9H, s), 1.68 (2H, qd), 1.99 (2H, d), 2.79 - 2.96 (3H, m), 3.70 (3H, s), 4.28 (2H, m), 6.24 (1H, s), 7.19 (1H, m), 7.39 - 7.44 (1H, m), 7.45 (1H, m); m / z: ES+[M+H]+= 393.3. Intermediate 13c: ter-butyl 4-[6-(2,4-dioxo-1,3-diazinan-1-yl)-1-methyl-1H-indol-2-yl]piperidine-1carboxylate

[00738] tert-butyl 4-(6-bromo-1-methyl-1H-indol-2-yl)piperidine-1-carboxylate (10.82 g, 27.51 mmol) was dissolved in 1,4-dioxane (180 ml) followed by the addition of hexahydropyrimidine-2,4-dione (9.42 g, 82.53 mmol), K2CO3 (11.41 g, 82.53 mmol) and tert-butylBrettPhos (1.33 g, 2.75 mmol). The mixture was degassed with nitrogen, then tert-butylBrettPhos Pd G3 (2.350 g, 2.75 mmol) was added and the mixture was stirred at 100 °C for 42 h. The reaction mixture was cooled, water (180 ml) and 2-MeTHF (180 ml) were added, and the layers were separated. The organic layer was washed with water (180 ml), NaCl solution (50 ml), dried with MgSO4, filtered, and evaporated to produce the crude product as a dark brown solid. The solid was Petition 870250080967, dated 09 / 09 / 2025, p. 197 / 523 188 / 482 transformed into an aqueous paste in EtOAc (30 ml) and the resulting brown suspension was filtered and washed with EtOAc (10 ml) to yield the title compound (6.59 g, 56.2%) as a pale brown solid. 1H-NMR dd), 7.37 (1H, d), 7.43 (1H, d), 10.26 (1H, s); Example 13: 4-chloro-7-[(3S)-3-{4-[4-({4-[6-(2,4-dioxo-1,3-diazinan-1-yl)-1-methyl-1Hmdol-2-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidm-1-yl]-1H-indole-3carbonitrile

[00739] tert-butyl 4-[6-(2,4-dioxo-1,3-diazinan-1-yl)-1-methyl-1H-indol-2yl]piperidine-1-carboxylate (1.55 g, 3.64 mmol) and intermediate 11c (2.1 g, 3.64 mmol) were heated in formic acid (20 ml, 3.64 mmol) at 40 °C for 2 h. The reaction was then cooled and evaporated to produce a residue which was diluted with NMP (20 ml). The resulting mixture was stirred at 40 °C for 16 h. The reaction mixture was then poured into Na2CO3 solution (150 ml) and the precipitate was collected by filtration, washed with water (50 ml) and dried under vacuum to produce the crude product. The crude product was purified by flash chromatography on silica, gradient elution of DCM from 0 to 10% in EtOH to produce the product which was transformed into an aqueous paste in MeCN and vacuum filtered to yield the title compound (1.10 g, 39.9%) as a pale yellow solid.RMN de 1H δ 1.12-1.28 (2H, m), 1.471.58 (1H, m), 1.58-1.73 (3H, m), 1.73-1.88 (3H, m), 1.88-1.99 (4H, m), 2.04 (2H, t), 2.18 (2H, d), 2.53-2.69 (4H, m), 2.73 (3H, t), 2.85-3.05 (3H, m), 3.30 (1H, d), 3.36 (1H, d),3.61 (2H, d), 3.68 (3H, s), 3.78 (2H, t), 6.22 (1H, s), 6.79. Petition: 870250080967, on September 9, 2025, page. 198 / 523 189 / 482 6,9 (3H, m), 6,93 (1H, dd), 7,14 (3H, dd), 7,36 (1H, d), 7,42 (1H, d), 8,31 (1H, s), 10,30 (1H, s), 12,28 (1H, s); m / z; ES+[M+H]+= 757,4. Example 14 Example 14a: 1-[1-metil-2-(piperidin-4-il)-1 H-indol-6-il]-1,3-diazinano-2,4-diona tosilato

[00740] A mixture of intermediate 13c (1.6 g, 3.75 mmol) and 4-methylbenzenesulfonic acid hydrate (0.856 g, 4.50 mmol) in MeCN (16.0 ml) was stirred at 70 °C for 2.5 h. The reaction mixture was cooled to room temperature, diluted with MTBE (16 ml), and stirred for 15 min. The solid was filtered, washing the solid with excess MTBE. The solid was dried under vacuum at 40 °C to yield the title compound (1.65 g, 88%) as a creamy solid. 1H NMR δ 1.71 - 1.85 (2H, m), 2.12 (2H, m), 2.29 (3H, m), 2.74 (2H, t), 3.03 - 3.24 (3H, m), 3.41 (1H, m), 3.71 (3H, s), 3.79 (2H, t), 6.26 (1H, s), 7.45 - 7.52 (3H, m); m / z: ES+[M+H]+= 327.3. Example 14: 4-chloro-7-[(3S)-3-{4-[4-({4-[6-(2,4-dioxo-1,3-diazinan-1-yl)-1-methyl-1 Hindol-2-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl]-1 H-indazol3-carbonitrile

[00741] A suspension of intermediate 9 h (1.38 g, 3.08 mmol) and 1-[1-methyl-2-(piperidin-4-yl)-1 H-indol-6-yl]-1,3-diazinane-2,4-dione TsOH (1.61 g, 3.23 mmol) in NMP (14.0 ml) was stirred at RT for 18 h. Petition 870250080967, dated 09 / 09 / 2025, p. 199 / 523 190 / 482 Sodium triacetoxyborohydride (0.78 g, 3.70 mmol) was added and the solution was stirred at room temperature for 2 h. The reaction mixture was rapidly cooled with water (40 ml) and the suspension was stirred at room temperature for 30 min. The solid was collected by filtration and washed with water. The solid was dissolved in DCM:IPA (3:1, 150 ml) and washed with NaHCO3 solution (150 ml), NaCl solution (100 ml), dried with a phase separation cartridge and evaporated to dryness to yield the crude product. The crude product was purified by flash chromatography on silica, gradient elution of 0 to 100% EtOAc in heptane followed by 0 to 10% MeOH in DCM to produce the desired product, which was transformed into an aqueous paste in MeCN (30 ml) at 80 °C for 3 h, then allowed to cool to room temperature for 18 h. The solid was vacuum filtered to yield the title compound (1.27 g, 54.4%) as a pale pink solid.1H NMR δ 1.16 - 1.28 (2H, m), 1.53 - 1.73 (4H, m), 1.76 - 1.98 (7H, m), 2.07 - 2.17 (2H, m), 2.25 (2H, d), 2.56 - 2.65 (2H, m), 2.66 - 2.84 (5H, m), 2.93 - 3.04 (3H, m), 3.47 - 3.57 (2H, m), 3.63 (2H, d), 3.68 (3H, s), 3.78 (2H, t), 6.23 (1H, s), 6.85 - 6.91 (3H, m), 6.93 (1H, dd), 7.18 (2H, d), 7.24 (1H, d), 7.36 (1H, s), 7.42 (1H, d), 10.27 (1H, s), 14.43 (1H, s); m / z: ES+[M+H]+= 758.4. Example 15: 7-(4:{42[4-£{42[2-(2J6-dioxOpiperidin-3yl)-7-methoxy4-oxO-:2J3^ isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-4-methyl1H-indol-3-carbonitrile

[00742] Intermediate 8b was reacted with Intermediate 7c using the general synthetic method illustrated by Example 7 after purification by HPLC (Column A, Eluent A) to yield the title compound (formate salt) (31 mg, 18%) as a white solid. 1H NMR δ 1.20 - 1.27 (3H, m), 1.68 Petition 870250080967, dated 09 / 09 / 2025, p. 200 / 523 191 / 482 (2H, s), 1.82 (4H, d), 1.95 (3H, s), 2.23 (2H, s), 2.31 (1H, d), 2.51 (4H, s), 2.56 - 2.68 (7H, m), 2.74 (2H, t), 2.88 (1H, q), 3.30 (2H, s), 3.38 (2H, d), 3.64 (2H, d), 3.84 (3H, s), 4.05 - 4.27 (2H, m), 4.96 (1H, dd), 6.49 (1H, s), 6.61 (1H, s), 6.77 (1H, d), 6.89 (3H, dd), 7.13 (2H, d), 8.16 (1H, d), 10.91 (1H, s), 11.90 (1H, s); m / z: ES+ [M+H]+ = 769.4. Examples 16 and 17

[00743] The enantiomers of Example 7 were separated by CFS purification on a Sepiatec 100 CFS using Regis (R,R) Whelk-01 CFS conditions, 21.1 x 250 mm, 5 microns, 50% MeOH / MeCN 3:7 / 50% scCO2 at a flow rate of 60 ml / min, 40 °C to yield, in order of elution, Example 16 (isomer 1, 12 mg, 28.6%) and Example 17 (isomer 2, 13 mg, 31.0%) as white solids. Example 16: 4-chloro-7-[4-(4-{4-[(4-{2-[(3R*)-2,6-dioxopiperidin-3-il]-7-metoxi-1-oxo2,3-di-hidro-1H-isoindol-5-il}piperazin-1-il)metil]piperidm-1il}fenil)piperidin-1-il] -1H-indol-3-carbonitrila

[00744] RMN of 1H δ 1.26 (2H, s), 1.70 (1H, s), 1.84 (4H, s), 1.97 (3H, d), 2.24 (3H, d), 2.54 - 2.65 (4H, m), 2.72 - 2.85 (2H, m), 2.88 (1H, d), 3.43 (2H, d), 3.65 (2H, d), 3.84 (3H, s), 4.11 (1H, d), 4.24 (1H, d), 4.97 (1H, dd), 6.50 (1H, s), 6.62 (1H, s), 6.87 (1H, d), 6.91 (2H, d), 7,15 (3H, dd), 8,32 (1H, s), 10,90 (1H, s), 12,26 (1H, s); m / z: ES+ [M+H]+ = 789,6; >99% de ee. Example 17: 4-chloro-7-[4-(4-{4-[(4-{2-[(3S*)-2,6-dioxopiperidin-3-il]-7-metoxi-1-oxo2,3-di-hydro-1 H-isoindol-5-il}piperazin-1-il)metil]piperidin-1il}fenil)piperidin-1-il]-1H-indol-3-carbonitrila Petition: 870250080967, on September 9, 2025, page. 201 / 523 192 / 482 [estereoquímica absolute but not confirmed]

[00745] 1H NMR δ 1.26 (2H, s), 1.70 (1H, s), 1.84 (4H, s), 1.98 (3H, d), 2.24 (2H, d), 2.31 (1H, s), 2.62 (4H, d), 2.73 - 2.83 (2H, m), 2.83 - 2.95 (1H, m), 3.43 (2H, d), 3.65 (2H, d), 3.84 (3H, s), 4.11 (1H, d), 4.24 (1H, d), 4.97 (1H, dd), 6.50 (1H, s), 6.62 (1H, s), 6.89 (3H, dd), 7.15 (3H, dd), 8.32 (1H, s), 10.90 (1H, s), 12.26 (1H, s); m / z: ES+[M+H]+= 789.6; >99% of ee. Examples 18 and 19:

[00746] The enantiomers of Example 1 were separated by CFS purification on a Sepiatec 100 CFS using Regis (R,R) Whelk-01 CFS conditions, 21.1 x 250 mm, 5 microns, 50% MeOH / MeCN 3:7 / 50% scCO2 at a flow rate of 60 ml / min, 40 °C to yield, in order of elution, Example 18 (isomer 1, 410 mg, 20.8%) and Example 19 (isomer 2, 400 mg, 20.3%) as white solids. Example 18: 4-chloro-7-[4—4J4[(4-{2-[(3R_*)^2J6-dioxopiperidin-32ilL1-o^ hidro-1 H-isoindol-5-il}piperazin-1-il)methyl]piperidin-1-il} fenil)piperidin-1-il]-1 H-indol-3 -carbonitrila [estereoquímica absolute but not confirmed]

[00747] RMN de 1H δ 1.25 (3H, s), 1.70 (1H, s), 1.84 (4H, s), 1.97 (4H, d), 2.24 (2H, d), 2.35 - 2.43 (2H, m), 2.55 - 2.65 (3H, m), 2.78 (2H, t), 2.84 2.97 (1H, m), 3.43 (2H, d), 3.65 (2H, d), 4.22 (1H, d), 4.34 (1H, d), 5.05 (1H, dd), 6.86 (1H, d), 6.91 (2H, d), 7.07 (2H, d), 7.11 - 7,19 (3H, m), 7.53 (1H, d), Petition: 870250080967, on September 9, 2025, page. 202 / 523 193 / 482 8,31 (1H, s), 10,94 (1H, s), 12,26 (1H, s); m / z: ES+[M+H]+= 759,7; >99% de ee. Example 19: 4-chloro-7-[4-(4-{4-[(4-{2-[(3S*)-2,6-dioxopiperidin-3-il]-1-oxo-2,3-di-hidro1H-isoindol-5-il}pipeΓαzin-1-iDmetillpperidin-1-il}fenil)piperid^ indol-3-carbonitrila [estereoquímica absolute but not confirmed]

[00748] NMR of 1H δ 1.16 - 1.32 (2H, m), 1.70 (1H, s), 1.78 - 1.9 (4H, m), 1.97 (3H, d), 2.24 (2H, d), 2.37 (2H, dd), 2.5 - 1.9 (2.6 m), (2H, d), 2.78 (2H, t), 2.84 - 2.96 (1H, m), 3.43 (2H, d), 3.65 (2H, d), 4.22 (1H, d), 4.34 (1H, d), 5.05 (1H, dd), 6.87 (1H, d), (7.7 H, 7). (2H, d), 7.15 (3H, dd), 7.53 (1H, d), 8.32 (1H, s), 10.94 (1H, s), 12.26 (1H, s); m / z: ES+[M+H]+= 759.7; >99 % of ee. Example 20: 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo-2,3-di-hydro-1 Hisoindol-5-ylJpiperazineΣEyl}methyl)piperidine1-illfeml}piperidine^^ 1H-indole-3 -carbonitrile

[00749] Intermediate 2c was reacted with Intermediate 7c using the general synthetic method illustrated by Example 7 after purification by HPLC (Column A, Eluent A) to yield the title compound as a formate salt (20 mg, 14%) as a white solid. 1H NMR δ 1.24 (2H, d), 1.69 (1H, s), 1.85 (4H, s), 1.88 - 2.05 (3H, m), 2.23 (2H, d), 2.25 - 2.37 (1H, Petition 870250080967, dated 09 / 09 / 2025, page 203 / 523 194 / 482 m), 2.56 - 2.74 (4H, m), 2.78 (2H, d), 2.88 (1H, d), 3.30 (8H, d), 3.39 (1H, s), 3.65 (3H, d), 3.84 (3H, s), 4.03 - 4.29 (2H, m), 4.91 - 5.03 (1H, m), 6.50 (1H, s), 6.62 (1H, s), 6.77 - 6.87 (1H, m), 6.87 - 7.00 (3H, m), 7.14 (2H, d), 8.28 (1H, s), 10.92 (1H, s), 12.26 (1H, s); m / z: ES+[M+H]+= 773,0. Example 21 Intermediate 21a: Benzyl (3R)-3-(4-bromophenyl)piperidine-1-carboxylate

[00750] (R)-3-(4-bromophenyl)piperidine oxalate was reacted with benzyl carbonhydrochloride using the general synthetic method illustrated by Example 1c to yield the title compound (1.0 g, 64.2%) as a colorless oil. 1H NMR δ 1.4-1.54 (1H, m), 1.58-1.67 (1H, m), 1.67-1.77 (1H, m), 1.87 (1H, dd), 2.59-2.71 (1H, m), 2.87 (2H, s), 3.9-4.12 (2H, m), 5.09 (2H, d), 7.24 (2H, d), 7.34 (5H, q), 7.47-7.53 (2H, m); m / z: ES+[M+H]+= 374.0. Intermediate 21b: Benzyl (3R)-3-{4-[4-(dibutoxymethyl)piperidin-1-yl]phenyl}piperidine-1-carboxylate

[00751] Benzyl (3R)-3-(4-bromophenyl)piperidine-1-carboxylate was reacted with 4-(dibutoxymethyl)piperidine using the general synthetic method illustrated by Example 11A to yield the title compound (462 mg, 32.1%) as a yellow oil. 1H NMR δ 0.88 (6H, t), 1.24–1.37 (7H, m), 1.41 Petition 870250080967, dated 09 / 09 / 2025, p. 204 / 523 195 / 482 1.54 (6H, m), 1.54-1.76 (6H, m), 1.84 (1H, d), 2.52-2.59 (2H, m), 3.35-3.45 (2H, m), 3.51-3.6 (2H, m), 3.63 (2H, d), 4.01 (2H, t), 4.18 (1H, d), 5.08 (2H, s), 6.85 (2H, d), 7.07 (2H, d), 7.27-7.47 (5H, m); m / z: ES+[M+H]+= 537,2. Intermediário 21c: 4-(dibutoximetil)-1-{4-[(3 R )-piperidin-3-il]fenil}piperidina

[00752] (3 R )-3-{4-[4-(dibutoximetil)piperidin-1-il]fenil}piperidina-1 carboxylate benzyl to reagido com Pd / C (10%) and the price is used and the other synthetic germs are attached to the original 11B to render or composto do título (300 mg, 87,0%) combined with olive oil. RMN de 1H δ 0.88 (6H, t), 1.231.4 (7H, m), 1.41-1.55 (6H, m), 1.58-1.89 (5H, m), 2.42 (3H, q), 2.54 (2H, d), 2.90 (2H, d), 3.34-3.43 (2H, m), 3.52-3.57 (2H, m), 3.58-3.65 (2H, m), 4.18 (1H, d), 6.76-6.9 (2H, m), 6.99-7.1 (2H, m); m / z: ES+[M+H]+= 403.2. Intermediário 21d: 4-chloro-7-[(3R)-3-{4-[4-(dibutoxymethyl)piperidin-1-yl]phenyl}piperidin-1-yl]1H-indol-3-carbonitrile

[00753] 4-(dibutoxymethyl)-1-{4-[(3R)-piperidin-3-yl]phenyl}piperidine was reacted with intermediate 1b using the general synthetic method illustrated by example 11C to yield the title compound (60 mg, 27.9%) as a solid. Petition 870250080967, dated 09 / 09 / 2025, p. 205 / 523 196 / 482 brown. 1H NMR δ 0.89 (6H, t), 1.3-1.42 (5H, m), 1.48 (5H, q), 1.72 (3H, d), 1.8-2.06 (4H, m), 2.66 (3H, d), 3.00 (1H, s), 3.41 (5H, s), 3.5-3.72 (4H, m), 4.19 (1H, d), 6.86 (3H, t), 7.15 (3H, t), 8.31 (1H, d), 12.28 (1H, s); m / z: ES+ [M+H]+ = 577.2. Example 21: 4-chloro-7-[(3R)-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro1H-isoindol-5-ylpiperazin-1-yl}methyl)piperidin-1-yl]phenyl}p iperidin-1-yl]-1 HindoE^carbonitrile

[00754] Intermediate 21d was reacted with Intermediate 1i using the general synthetic method illustrated by Example 7 after purification by HPLC (Column A, Eluent A) to yield the title compound in the form of a formate salt (30 mg, 28%) as a white solid. 1H NMR δ 1.21 (2, q), 1.48-1.62 (1H, m), 1.68 (1H, s), 1.72-2.03 (7H, m), 2.21 (2H, d), 2.28-2.48 (2H, m), 2.5-2.75 (6H, m), 2.84-3.07 (2H, m), 3.28 (5H, s), 3.35 (2H, s), 3.62 (2H, d), 4.20 (1H, d), 4.33 (1H, d), 5.05 (1H, dd), 6.85 (3H, dd), 7.07 (2H, d), 7.15 (3H, dd), 7.52 (1H, d), 8.31 (1H, d), 10.95 (1H, s), 12.28 (1H, d); m / z: ES+ [M+H]+ = 759.4. Example 22 Intermediate 22a: ter -butyl 4-(4-{1-[(benzyloxy)carbonyl]piperidin-4-yl}phenyl)piperazine-1-carboxylate Petition 870250080967, dated 09 / 09 / 2025, p. 206 / 523 197 / 482

[00755] Pd(t-Bu3P)2 (0.137 g, 0.27 mmol) was added to tri-tert-butylphosphonium tetrafluoroborate (0.078 g, 0.27 mmol), CS2CO3 (1.741 g, 5.34 mmol), tert-butyl piperazine-1-carboxylate (0.498 g, 2.67 mmol), and intermediate 1c (1.00 g, 2.67 mmol) in 1,4-dioxane (10 mL) under nitrogen. The resulting mixture was stirred at 100 °C for 19 h. The reaction was then cooled to TA and the solvent was evaporated to yield the crude product. The crude product was purified by flash chromatography on silica, gradient elution from 0 to 40% EtOAc in Et2O to yield the title compound (1.0 g, 78%) as a yellow solid. m / z: ES+ [M+H]+ = 480.4. Intermediate 22b: tert-butyl 4-[4-(piperidin-4-yl)phenyl]piperazine-1-carboxylate

[00756] Pd / C (10%, 0.67 g, 0.63 mmol) and tert-butyl 4-(4-{1[(benzyloxy)carbonyl]piperidin-4-yl}phenyl)piperazine-1-carboxylate (1.00 g, 2.08 mmol) in MeOH:EtOAc (1:5, 1.2 ml) was stirred under a hydrogen atmosphere at room temperature for 2 h. The mixture was filtered through Celite® and evaporated to dryness to yield the title compound which was used without further purification. m / z: ES+[M+H]+= 346.3. Intermediate 22c: tert-butyl 4-{4-[1-(3-cyano-4-fluoro-1H-indol-7-yl)piperidin-4-yl]phenyl}piperazine-1carboxylate Petition 870250080967, dated 09 / 09 / 2025, p. 207 / 523 198 / 482

[00757] (DiMeIHeptCl)Pd(cinnamyl)Cl (152 mg, 0.14 mmol) was added to tert-butyl 4-(4-(piperidin-4-yl)phenyl)piperazine-1-carboxylate (500 mg, 1.45 mmol), intermediate 2b (346 mg, 1.45 mmol) and CS2CO3 (1.6 g, 5.07 mmol) in 1,4-dioxane (1 ml) under nitrogen and stirred at 100 °C for 3 h. The reaction was cooled to TA and the solvent was evaporated to yield the crude product. The crude product was purified by flash chromatography on silica, gradient elution from 0 to 50% EtOAc in Et2O to yield the title compound as a yellow solid. m / z: ES+ [M+H]+ = 504.3. Intermediate 22d: 3-{5-[4-(dibutoxymethyl)piperidin-1-yl]-1-oxo-1J32dihydro-2H-isoindol-2yl}piperidin-2,6-dione

[00758] Pd-PEPPSI-IHeptCl (0.23 g, 0.24 mmol) was added to a degassed mixture of intermediate 1 h (1.5 g, 4.64 mmol), 4-(dibutoxymethyl)piperidine (1.5 g, 6.16 mmol) and CS2CO3 (4.54 g, 13.93 mmol) in 1,4-dioxane (45 ml) at room temperature under nitrogen. The resulting mixture was stirred at 100 °C for 3 h under nitrogen. The reaction mixture was cooled to room temperature, diluted with DCM (75 ml) and AcOH (10%, 50 ml). The organic layer was washed with NaHCO3 solution (50 ml), dried with MgSO4, filtered and evaporated to yield the crude product. The crude product was ground with EtOAc (15 ml) to yield a solid which was collected by filtration, washed with EtOAc (2 x 5 ml), Petition 870250080967, dated 09 / 09 / 2025, page 208 / 523 199 / 482 EtOAc: Et2Ü (1:1; 5 ml), Et2Ü (5 ml) and then a vácuo to render o composto do the tulo (1.66 g, 73.6 %) combined with solid branco. RMN de 1H δ 0.89 (6H, t), 1.23 - 1.42 (6H, m), 1.43 - 1.56 (4H, m), 1.67 - 1.85 (3H, m), 1.96 (1H, m), 2.28 2.44 (1H, m), 2.55 - 2.64 (1H, m), 2.72 - 2.84 (2H, m), 2.90 (1H, m), 3.40 (2H, dt), 3.56 (2H, dt), 3.89 (2H, d), 4.09 - 4.25 (2H, m), 4.32 (1H, d), 5.04 (1H, dd), 7.04 (2H, d), 7,50 (1H, d), 10,91 (1H, s); m / z: ES+[M+H]+= 486,0. Example 22: 7Σ(4:{42[42({l·-[22(2J62dioχΌpiperidin=32il)r1-oxoΣ232di-hid^ il]piperidin-4-il}metil)piperazin212il]fenil}piperidin-12iI)-4-fluoro21H-indol3-carbonitrila

[00759] Intermediate 22c was reacted with intermediate 22d using the general synthetic method illustrated by Example 7 after purification by HPLC (Column A, Eluent A) to yield the title compound in the form of a formate salt (25.0 mg, 14.12%) as a yellow solid. 1H-NMR 2.85-2.97 (1H, m), 3.06-3.13 (4H, m), 3.26-3.38 (5H, m), 3.88 (2H, d), 4.19 (1H, d), 4.32 (1H, d), 5.05 (1H, dd), 6.82 (1H, dd), 6.87-6.97 (3H, m), 7.04 (2H, d), 7.14 (2H, d), 7.50 (1H, d), 8.27 (1H, s), 10.95 (1H, s), 12.26 (1H, s); m / z: ES+[M+H]+= 743.5. Example 23 Intermediate 23a: 7-[(3>S)-3-{4-14-dibutoxymethyl)piperidin-1-yl]phenyl}piperidin-1-yl]-4-fluoro2 1H-indol-3-carbonitrile Petition 870250080967, dated 09 / 09 / 2025, p. 209 / 523 200 / 482

[00760] LHMDS (1 M in THF, 2.61 ml, 2.61 mmol) was added to intermediate 11b (300 mg, 0.75 mmol), intermediate 2b (178 mg, 0.75 mmol), and Pd-PEPPSI-IHeptCl (21.74 mg, 0.02 mmol) in THF (2 ml) under nitrogen. The resulting mixture was stirred at 60 °C for 2 h. The reaction mixture was rapidly cooled with saturated NH4Cl (25 ml) and extracted with EtOAc (3 x 50 ml). The organic layer was dried with Na2SO4, filtered, and evaporated to yield the crude product. The crude product was purified by flash chromatography on silica, gradient elution from 0% EtOAc to 60% Et2O to yield the title compound (280 mg, 67.0%) as a yellow solid. 1H NMR δ 0.87 (6H, t), 1.27-1.4 (6H, m), 1.42-1.52 (5H, m), 1,591.76 (3H, m), 1.79-1.98 (3H, m), 2.54 (2H, dd), 2.59-2.7 (2H, m), 2.94-3.04 (1H, m), 3.27 (2H, d), 3.35-3.41 (2H, m), 3.54 (2H, dt), 3.62 (2H, d), 4.16 (1H, d), 6.74-6.93 (4H, m), 7.11-7.18 (2H, m), 8.26 (1H, d), 12.26 (1H, s); m / z: ES+[M+H]+= 561,0. Example 23: 7-[(3 5)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1-yl]piperidine1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl]-4-carbonitrile-3-H Petition 870250080967, dated 09 / 09 / 2025, p. 210 / 523 201 / 482

[00761] Formic acid (2 ml, 52.15 mmol) was added to 7-[(3S)-3{4-[4-(dibutoxymethyl)piperidin-1-yl]phenyl}piperidin-1-yl]-4-fluoro-1H-indol-3-carbonitrile (150 mg, 0.27 mmol) at room temperature and the mixture was stirred for 1 h. The solvent was then evaporated and the residue combined with intermediate 5f (84 mg, 0.27 mmol) at MPN (2 ml). The mixture was stirred at room temperature for 1 h. Purification of the reaction mixture by preparative HPLC (Column A, Eluent A) yielded the title compound as a formate salt (27.0 mg, 13.89%) as a white solid. 1H NMR δ 1.21 (2H, q), 1.47-1.6 (1H, m), 1.65 (1H, s), 1.76-1.88 (3H, m), 1.88-2.06 (6H, m), 2.16 (2H, t), 2.23 (2H, d), 2.54-2.72 (4H, m), 2.76 (2H, t), 2.89-3.07 (3H, m), 3.40 (3H, s), 3.62 (2H, d), 3.77 (2H, t), 4.3-4.46 (1H, m), 6.41 (1H, d), 6.70 (1H, dd), 6.84 (3H, dd), 6.96 (1H, d), 7.14 (3H, t), 7.47-7.6 (2H, m), 8.17 (1H, s), 10.34 (1H, s); m / z: ES+[M+H]+ = 727.0. Example 24: 7-L(3Sj-3-{4-[4-(;4-[2-(2.6-dio\opiperidin-3-yl)-1-o\o-2,3-dihydro-1 Hisoindol-5-yl]piperazin-1-yl} methyl)piperidin-1-yl]phenyl}p iperidin-1-yl]-4-fluoro1H-indol-3-carbonitrile

[00762] Intermediate 23a (140 mg, 0.25 mmol) was stirred in formic acid (1 ml) at room temperature for 1 h, then evaporated to dry. Intermediate 1i (107 mg, 0.25 mmol) was also stirred in formic acid (1 ml) at room temperature for 1 h, then evaporated to dry. The two residues were then combined in MPN (2 ml) and the resulting mixture was stirred at room temperature for 1 h. The reaction mixture was purified by C18 flash chromatography, 5% to 100% MeCN gradient elution in water (1% NH4HCO3) to yield the Petition 870250080967, dated 09 / 09 / 2025, page 211 / 523 202 / 482 Composto do título (53.0 mg, 28.6%) combined with solid branco. RMN de 1H δ 1.11-1.32 (2H, m), 1.44-1.6 (1H, m), 1.66 (1H, s), 1.74-2 (6H, m), 2.20 (2H, d), 2.3-2.43 (1H, m), 2.48 (3H, d), 2.52-2.72 (6H, m), 2.84-3.04 (2H, m), 3.23-3.33 (6H, m), 3.61 (2H, d), 4.16-4.38 (2H, m), 5.05 (1H, dd), 6.79 (1H, dd), 6.83-6.93 (3H, m), 7.05 (2H, d), 7.15 (2H, d) 7.52 (1H, d), 8.26 (1H, s), 10.96 (1H, s), 12.27 (1H, s); m / z: ES+[M+H]+= 743,0. Example 25: 4-chloro-7-[(3 R )-3-{4-[4-({4-[4-(2,4-dioxo- 1,3-diazinan-1 -il)-1 H-indol-1 il]piperidin-1-il}metil)piperidin-1-il]fenil}piperidin-1-il]-1 H-indazol-3carbonitrila

[00763] The title compound was prepared according to the procedure described in Example 9, but using (S)-3-(4-bromophenyl)piperidine oxalate in step 9d. Purification by HPLC (Column A, Eluent A) yielded the title compound as a formate salt (43.0 mg, 33.4%) as a yellow solid; 1H NMR δ 0.85 (1H, q), 1.16-1.3 (2H, m), 1.52-1.72 (2H, m), 1.78-1.91 (2H, m), 1.9-2.1 (6H, m), 2.24 (4H, dd), 2.63 (2H, dd), 2.67-2.8 (4H, m), 3.02 (3H, d), 3.51 (3H, q), 3.64 (2H, d), 3.78 (2H, t), 4.39 (1H, tt), 6.42 (1H, d), 6.85-7 (4H, m), 7.11-7.3 (4H, m), 7.53 (2H, dd), 10.33 (1H, s); m / z: ES+[M+H]+= 744.5. Example 26: 4-chloro-7-[(3R)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1H-indol-1yl]piperidin-12yl}methyl)piperidin42yljphenyl}pperidin-^^carbonitrile Petition 870250080967, dated 09 / 09 / 2025, p. 212 / 523 203 / 482

[00764] Intermediate 21d was reacted with intermediate 5f using the general synthetic method illustrated by example 23 after purification by HPLC (Column A, Eluent A) to yield the title compound in the form of a formate salt (42.0 mg, 54.4%) as a white solid; 1H NMR δ 0.84 (1H,d), 1.22 (3H,d), 1.57 (1H,t), 1.66 (1H,s), 1.81 (3H,d), 1.94 (5H,d), 2.00 (1H,d), 2.07 (1H,s), 2.17 (2H,t), 2.24 (2H, d), 2.55-2.7 (3H, m), 2.76 (2H, t), 2.99 (3H, d), 3.63 (2H, d), 3.78 (2H, t), 4.37 (1H, s), 6.41 (1H, d), 6.85 (3H, dd), 6.96 (1H, d), 7.1-7.19 (4H, m), 7.47-7.56 (2H, m), 8.31 (1H, s), 10.32 (1H, s), 12.28 (1H, s); m / z: ES+[M+H]+= 743.0. Example 27 Intermediate 27a: tert-butyl 4-[4-(benzyloxy)phenyl]piperidine-1-carboxylate

[00765] Benzyl bromide (2.89 g, 16.87 mmol) was added to tert-butyl 4-(4-hydroxyphenyl)piperidine-1-carboxylate (3.6 g, 12.98 mmol) and K2CO3 (5.38 g, 38.94 mmol) in DMF (52 ml). The resulting mixture was stirred at room temperature for 5 h. The reaction mixture was diluted with EtOAc (200 ml), washed with water (100 ml) and NaCl solution (50 ml). The organic layer was dried with Na2SO4, filtered, and evaporated to yield the crude product. The crude product was purified by flash chromatography on silica, gradient elution of 0 to 20% EtOAc in Et2O to yield the title compound (4.50 g, 94%) as a white solid. 1H NMR δ 1.29 (11H, d), 1.59 (2H, d), 2.40 - 2.55 (1H, m), 2.65 (2H, s), 3.93 (2H, d), 4.94 (2H, d), 6.76 - 6.86 (2H, m), 6.97 - 7.08 (2H, m), 7.14 - 7.37 (5H, m); m / z: ES+[M+H]+= 353.2. Petition 870250080967, dated 09 / 09 / 2025, p. 213 / 523 204 / 482 Intermediate 27b: 4-[4-(benzyloxy)phenyl]piperidine

[00766] tert-butyl 4-[4-(benzyloxy)phenyl]piperidine-1-carboxylate (4.5 g, 12.25 mmol) was stirred in formic acid (50 mL) at room temperature for 2 h. The reaction mixture was then evaporated to dryness to yield the crude product. The crude product was purified by ion-exchange chromatography using an SCX column. The desired product was eluted from the column using 7 M NH3 / MeOH to yield the title compound (3.20 g, 98%) as a white solid. 1H-NMR m), 7.05 - 7.16 (2H, m), 7.24 - 7.47 (5H, m); m / z: ES+[M+H]+= 268.2. Intermediate 27c: 7-{42[42(benzyloxy)phenylpiperidin-12yl}-4-methyl-1H-indol-32carbonylyl1

[00767] Pd-PEPPSI-IPent (0.304 g, 0.31 mmol) was added to 4-[4(benzyloxy)phenyl]piperidine (3.20 g, 11.99 mmol), intermediate 8a (2.45 g, 10.42 mmol) and LHMDS (1 M in THF, 36.5 ml, 36.48 mmol) in 1,4-dioxane (25 ml) under nitrogen. The resulting mixture was stirred at 60 °C for 2 h. The reaction mixture was cooled to TA and then briskly cooled with water (5 ml). The solvent was removed under reduced pressure to yield the crude product. The crude product was purified by flash chromatography on silica, gradient elution from DCM at 0 to 100% in Et2O followed by EtOAc at 0 to 10% in DCM to yield the title compound (2.60 g, 59.2%) as a yellow solid. 1H NMR δ 1.85 (2H, d), 1.89 - 2.08 (2H, m), 2.60 (4H, s), 2.67 - 2.82 (2H, m), 3.38 (2H, d), 5.09 (2H, s), 6.77 (1H, d), 6.88 (1H, d), 6.93 Petition 870250080967, dated 09 / 09 / 2025, p. 214 / 523 205 / 482 - 7,04 (2H, m), 7,17 - 7,28 (2H, m), 7,30 - 7,51 (5H, m), 8,17 (1H, d), 11,88 11,95 (1H, m); m / z: ES+[M+H]+= 422,3. Intermediário 27d: 7-{4-[4-(benziloxi)fenil]piperidin- 1-il}-4-metil-1-{[2(trimetilsilil)etoxi]metil}-1 H-indol-3-carbonitrila

[00768] Sodium hydride (0.144 g, 3.61 mmol) was added to 7-{4-[4(benzyloxy)phenyl]piperidin-1-yl}-4-methyl-1H-indol-3-carbonitrile (1.17 g, 2.78 mmol) in THF (18 ml) at 0 °C and stirred for 1 h. 2-(trimethylsilyl)ethoxymethyl chloride (0.591 ml, 3.33 mmol) was added and the resulting solution was stirred at room temperature for 2 h. The reaction mixture was rapidly cooled with water and the reaction was evaporated to yield the crude product. The crude product was purified by flash chromatography on silica, 0 to 90% DCM gradient elution in Et2O to yield the title compound (1.3 g, 85%) as a white solid. 1H NMR δ -0.09 (9H, s), 0.76 - 0.87 (2H, m), 1.85 (4H, s), 2.57 (4H, d), 2.84 (2H, s), 3.16 (2H, d), 3.48 - 3.59 (2H, m), 5.09 (2H, s), 5.97 (2H, s), 6.92 - 7.04 (3H, m), 7.12 (1H, d), 7.18 - 7.26 (2H, m), 7.28 - 7.51 (5H, m), 8.36 (1H, s); m / z: ES+[M+H]+= 552.4. Intermediate 27e: 7-[4-(4-hydroxyphenyl)piperidin-1-yl]-4-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}1H-indol-3-carbonitrile

[00769] Pd / C (10%, 1.24 g, 11.65 mmol) was added to 7-{4-[4(benzyloxy)phenyl]piperidin-1-yl}-4-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H Petition 870250080967, dated 09 / 09 / 2025, p. 215 / 523 206 / 482 indole-3-carbonitrile (1.24 g, 2.25 mmol) in EtOAc (60 ml) under hydrogen and stirred under TA for 2 h. The reaction mixture was filtered through Celite® and the solvent was evaporated to yield the title compound (0.94 g, 91%) as a white solid. 1H NMR (CDCl3) δ -0.03 (9H, s), 0.83 - 1.01 (2H, m), 1.83 - 2.01 (4H, m), 2.56 - 2.69 (1H, m), 2.77 (3H, s), 2.93 (2H, td), 3.29 (2H, d), 3.50 - 3.61 (2H, m), 6.06 (2H, s), 6.79 - 6.90 (2H, m), 6.96 - 7.04 (1H, m), 7.12 (1H, d), 7.15 - 7.23 (2H, m), 7.73 (1H, s) OH not observed; m / z: ES+[M+H]+= 462.3. Intermediate 27f: 7-(42{4:2l3-£1J3-dioxolan=22ylJpOpoxyJphenyl}piperid:in-12yl^^ (trimethylsilyl)ethoxy]methyl}-1 H-indol-3-carbonitrile

[00770] K2CO3 (0.808 g, 5.85 mmol) was added to 7-[4-(4-hydroxyphenyl)piperidin-1-yl]-4-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indol-3-carbonitrile (0.90 g, 1.95 mmol) and 2-(3-bromopropyl)-1,3-dioxolane (0.760 g, 3.90 mmol) in DMF (10 ml). The resulting mixture was stirred at 80 °C for 8 h. The reaction mixture was cooled to room temperature and purified by C18 flash chromatography, 0 to 100% MeOH gradient elution in water (0.1% NH4HCO3) to yield the title compound (0.75 g, 66.8%) as a yellow solid. 1H NMR (MeOD) δ 0.70 (9H, s), 1.60 (2H, t), 2.02 (1H, s), 2.46 - 2.60 (3H, m), 2.63 (5H, s), 3.41 (3H, s), 3.90 - 4.00 (2H, m), 4.11 (2H, s); m / z: ES+[M+H]+= 576.5. Intermediate 27g: Petition 870250080967, dated 09 / 09 / 2025, p. 216 / 523 207 / 482 7-(4-{4-[3-(1,3-dioxolan-2-yl)propoxy]phenyl}piperidin-1-yl)-4-methyl-1H-indol3-carbonitrile

[00771] Tetrabutylammonium fluoride (1 M in THF, 9.3 mL, 9.38 mmol) was added to 7-(4-{4-[3-(1,3-dioxolan-2-yl)propoxy]phenyl}piperidin-1-yl)-4-methyl-1-{[2-(trimethylsilyl)ethoxy]met...

Claims

CLAIMS 1. Compound, characterized in that it is of formula (I): (I) or a pharmaceutically acceptable salt thereof, wherein: X1 is CH or N; p is 0, 1 or 2; wherein: each R1 is a substituent on any C atom and is independently selected from F, Cl, C1-3 alkyl and C1-3 alkoxy, wherein said C1-3 alkyl and C1-3 alkoxy may be independently or optionally substituted by one or more F; RN is selected from H and Me; n is 0, 1 or 2; m is 0 or 1; Q1 is CH or N; when neither are both different from 0, Q2 is CH or N; when neither are both 0, Q2 is CH; when n is 0 or 1, Q3 is CH; when n is 2 and Q2 is N, Q3 is CH; when n is 2 and Q2 is CH, Q3 is CH or O; R2a and R2b are substituents on the same or different C atoms, except on Q1 or Q2, each independently selected from H, F and C1-3 alkyl, or R2a and R2b together form a -(CH2)r- group, wherein r is 1, 2 or 3; Petition 870250080967, dated 09 / 09 / 2025, p. 493 / 523 2 / 30 Q4 is a single bond or -NR4C(=O);R4 is H or Me; 0, 1, or 2 of Y1, Y2, Y3, Y4, and Y5 is / are N, and otherwise is C; each R3 is a substituent on any C atom in Y1, Y2, Y3, Y4, and Y5, and is independently selected from F, Cl, CN, C1-3 alkyl, and C1-3 alkoxy, wherein said C1-3 alkyl and C1-3 alkoxy may independently or optionally be substituted by one or more F; q is 0, 1, or 2; wherein the Ligand is attached to any available C atom in Y4 and Y5; the Ligand is a saturated or partially or completely unsaturated structure comprising C and H atoms and at least one heteroatom, said structure having terminal bonding points 'a' and 'b' and a length of 5 to 26 atoms between 'a' and 'b'; wherein said structure may include one or more linear and / or branched chains and / or rings and is optionally replaced at any available C atom(s) by one or more F atoms; and W is a binding unit of the E3 ubiquitin ligase cereblon.

2. Compound of formula (I), or pharmaceutically acceptable salt thereof according to claim 1 or claim 2, characterized in that the ligand is a saturated or partially unsaturated structure and: (a) comprises C and H atoms and at least two heteroatoms; or (b) comprises C and H atoms and at least one nitrogen heteroatom in the form of a secondary or tertiary amine; or (c) includes at least one saturated or partially unsaturated heterocyclic group containing nitrogen with 4 to 12 atoms in the ring, or Petition 870250080967, dated 09 / 09 / 2025, page 494 / 523 3 / 30 an A1-CH2-CH2-A2 unit, wherein A1 and A2 are each independently selected from N and O.

3. Compound of formula (I), or pharmaceutically acceptable salt thereof according to claim 1 or claim 2, characterized in that the ligand has the formula: 'a' -Qa-QB-Qc- 'b' wherein: 'a' and 'b' represent the terminal attachment points; QA is -G-QH- or -G-(C1-5alkylene)-; QB is a direct linkage, -QB1-QB2-QB3- or C1-3alkylene optionally substituted by one or more F (e.g., 1 or 2); wherein: QB1 and QB3 each independently represent a direct linkage or C1-2alkylene; QB2 is QH, -O-CH2CH2-O-, -O- or -N(RJ)-, where RJ is H or C13alkyl; QC is -Qh-G- or -(C1-5alkylene)-G-; each G is independently a direct linkage, -CH2-, -O-, C(=O)- or -N(Rg)-, where RG is H or C1-3 alkyl; each QH is independently a saturated or partially unsaturated heterocyclic group containing nitrogen with 4 to 12 members; wherein the values ​​of QA, QB and QC are selected so that the Ligand does not contain any NN or NO linkages.

4. Compound of formula (I), or pharmaceutically acceptable salt thereof according to claim 3, characterized in that: (a) QB is a direct linkage, -CH2- or -CH2CH2-; and / or (b) QC is -QH-G- or -(C1-2-alkylene)-G-; and / or (c) each QH is independently selected from piperazin-1,4-di-yl, azetidin-1,3-di-yl, piperidin-1,4-di-yl, 1,4-diazepan-1,4-di-yl, 12-oxa3,9-diazaspiro[5.6]dodecan-3,9-di-yl, pirrolidin-1,3-di-yl, 3,9 Petition 870250080967, dated 09 / 09 / 2025, page. 495 / 523 4 / 30 diazaspiro [5.5 ]undecan-3,9-di-yl, 2,5-diazabicyclo[2.2.1]heptan-2,5-di-yl, 1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-2,5-di-yl, 3,6-dihydro-2 / 7pyridin-1,4-di-yl, morpholin-2,3-di-yl, 2-azaspiro[3.5]nonan-2,7-di-yl and 9azaspiro[5.5]undecan-3,9-di-yl.

5. Compound PROTAC or a pharmaceutically acceptable salt thereof, characterized in that it contains an E3 ubiquitin ligase cereblon binding unit and an AR binding unit of formula (Ia): (Ia) wherein R1, p, X1, RN, n, m, R2a, R2b, Q1, Q2, Q3, Q4, Y1, Y2, Y3, Y4, Y5, R3 eq are as defined in claim 1.

6. Compound of formula (I), or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, characterized as follows: 377777 represents a single covalent bond or a double covalent bond; 1 of Xa2, XB2, XC2 and XD2 is C and covalently bonded to YN; Petition 870250080967, dated 09 / 09 / 2025, p.496 / 523 5 / 30 0, 1 or 2 of Xa2, XB2, Xc2, XD2, XE2 and XF2 is / are N, wherein XE2 and XF2 are not both N, and otherwise are C; 1 or 2 of XG2, XH2 and XJ2 is / are N; and otherwise are C; each RAA is a substituent on any available C or N atom of Z - in each case independently selected from RAA1 optionally substituted by one or more RAA2; wherein RAA is additionally selected from RAA2 when RAA is a substituent on an available C atom of ZA; each RAA1 is independently C1-4 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 alkoxy C1-3 alkyl, carboxy C1-3 alkyl, C5-? carbocyclyl or a 4- to 6-membered heterocyclyl; each RAA2 is independently selected from F, Cl, Br, CN, NH2, C1-3 alkyl, O(C1-3 alkyl), NH(C1-3 alkyl) and N(C1-3 alkyl)2; said C1-3 alkyls being optionally substituted by one or more F; v is 0, 1 or 2; YN is 2,4-dioxo-hexahydropyrimidin-1-yl.

7. A pharmaceutically acceptable compound or salt thereof according to claim 6, characterized in that 1 of Xa2 and XB2 is C and covalently linked to Y and the other of Xa2 and XB2 is C; 0 or 1 of XC2 and XD2 is N and otherwise is / are C; 1 of XG2 and XJ2 is N and the other of XG2 and XJ2 is C; and XH2, XE2 and XF2 are all C.

8. Pharmaceutically acceptable compound or salt thereof according to claim 6, characterized in that W is W2-1 wherein: Petition 870250080967, dated 09 / 09 / 2025, page 497 / 523 6 / 30 XK and XL are N-linked and CH, N-linked and CMe or N-linked and C-linked, respectively; 1 of XM and Xo is C-2,4-dioxo-hexahydropyrimidin-1-yl (YN); 0 or 1 of XM and XN is CF; XN may be N if XM is not CF; the remainder of XN, XM and Xo is CH; and Xp is CH or CMe.

9. Compound of formula (I), or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, characterized in that W is Wl, which is: -Z-(RA)h wherein Z is: wherein: represents a single covalent bond or a double covalent bond; 0, 1 or 2 of Xa, Xb, Xc, Xd, Xe and XF is / are N, wherein XE and XF are not both N, and otherwise are C; 1 of XG, XH and XJ is C(O); 1 of XG, XH and XJ is N-(2,6-dioxopiperidin-3-yl)(Y); and 1 of XG, XH and XJ is selected from C(RT)2, -CH2CH2-, C(O), N(C1-3-alkyl), -O- and -N=, wherein each RT is selected from H, F, Me or together with the carbon of C(RT)2 form a cycloprop-1,1-di-yl group; wherein XG, XH and XJ are selected so that there are no two C(O) groups present in adjacent positions and that the N-(2,6-dioxopiperidin-3-yl) is not in a position adjacent to N(C1-3-alkyl) or O; Petition 870250080967, dated 09 / 09 / 2025, p.498 / 523 7 / 30 each Ra is independently a substituent on any available C atom in Xa, Xb, Xc or XD selected from F, Cl, C1-3 alkyl, C13 alkoxy, wherein said C1-3 alkyl and C1-3 alkoxy are independently optionally substituted by one or more F; h is 0, 1 or 2; and wherein the ligand is attached to any C atom in Xa, Xb, Xc or XD.

10. Compound of formula (I), or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, characterized in that W is W3, which is: -ZB wherein ZB is: XE3 is selected from C(=O) and CRe1RE2, wherein Re1 and RE2 are independently selected from the group consisting of H and C1-3 alkyl, or Re1 and RE2, taken together with the carbons to which they are attached, form a C3-6 cycloalkane ring; Y is N-(2,6-dioxopiperidin-3-yl); all of Xa3, Xb3, Xc3 and XD3 are C; a pair of Xa3 and Xb3, Xb3 and XC3 and XC3 and XD3 forms a five- or six-membered completely unsaturated or partially unsaturated N-containing heterocyclic ring, which is linked to the 'b' end of the ligand through an N atom; The others, including Xa3, Xb3, Xc3, and XD3, contain an Rb group, where each Rb is selected from H, F, Cl, C1-3 alkyl, and C1-3 alkoxy. Petition 870250080967, dated 09 / 09 / 2025, page 499 / 523 8 / 30 11. A pharmaceutically acceptable compound or salt thereof according to any of the preceding claims, characterized in that RN is H, ep is 0 or 1, R1 is selected from Cl, F and Me, and R1, if present, is linked in the para position relative to Q1.

12. A pharmaceutically acceptable compound or salt thereof according to any of the preceding claims, characterized in that X1 is N.

13. A pharmaceutically acceptable compound or salt thereof according to any one of claims 1 to 37, characterized in that Q1 is N, Q2 is CH and Q3 is CH, and are 1 and 1 or 2 and 0, respectively.

14. A pharmaceutically acceptable compound or salt thereof according to any of the preceding claims, characterized in that R2a and R2b are both H.

15. Pharmaceutically acceptable compound or salt thereof according to any of the preceding claims, characterized in that: (a) Q4 is a single bond; or (b) Q4 is an NR4C(=O) and R4 is H.

16. A pharmaceutically acceptable compound or salt thereof according to any of the preceding claims, characterized in that Y1, Y2, Y3, Y4 and Y5 are all C.

17. A pharmaceutically acceptable compound or salt thereof according to any of the preceding claims, characterized in that q is 0 or 1 and R3 (when present) is a substituent on any C atom in Y1, Y2, Y3, Y4 and Y5, which is F.

18. Pharmaceutically acceptable compound or salt thereof according to any of the preceding claims, characterized in that the binder is linked at Y5. Petition 870250080967, dated 09 / 09 / 2025, p. 500 / 523 9 / 30 19. A pharmaceutically acceptable compound or salt thereof according to any one of claims 1 to 34, characterized in that: X1 is N; p is 1; Rn is H; n is 2; m is 0; R2a and R2b are both H; Q4 is a simple connection; Y1, Y2, Y3 and Y4 are all CH; Y5 is C and has the ligand attached; eq is 0.

20. The compound according to claim 1, further characterized being selected from: 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidine-3-yl)-1-oxo-2,3-dihydropyl perylzi-1 H-iso-iso-iso methyl)piperidine-1-yl]phenyl}piperidin-1yl)-1 H-indole-3 -carbonitrile; 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1-carbon]phenyl}p hyperidin-1 -tril-yl-1-H-3-4flu 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1-carbon]phenyl}p hyperidin-1 -tril-yl-1-H-3-4flu 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1-carbon]phenyl}p hyperidin-1 -tril-yl-1-H-3-4fluPetition 870250080967, dated 09 / 09 / 2025, p. 501 / 523 10 / 30 4-chloro-7-(4-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol1-yl]piperidin- 1-yl}methyl)piperidin-1-yl]peridin-1}pyl H-indole-3carbonitrile; 7-(4-{4- [4-({4- [4-(2,4-dioxo-1-yl)-1 H-indol-1yl]piperidine-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-4-fluoro-1H-bonitrindol;carbon3-carbon 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1oxo-2,3-di-hydro-1 H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1yl] H-3-1-ylcarbonitril-1-1; 7-(4-{4- [4-({4- [4-(2,4-dioxo-1-yl)-1 H-indol-1yl]piperidine-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-4-methyl-1 H-indole;3carbonitrile 4-chloro-7-[(3 5)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl];-1H-indazole4-chloro-7-[(3 S)-3-{4-[4-({4-[2-(2,6-dioxopiperidm-3-yl)-1-oxo2,3-di-hydro-1 H-isoindol-5-yl]piperazin-1-yl}methyl)piperidine-1yl] H-phenyl-indacarzotripyridine-1; 4-chloro-7-[(3 5)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl];-1H-indole 4-chloro-7-[(3 S)-3-{4-[4-({4-[2-(2,6-dioxopiperidm-3-yl)-1-oxo2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1yl] H-phenyl-yl-indotripyridine-1; 4-chloro-7-[(3 5)-3-{4-[4-({4-[6-(2,4-dioxo-1,3-diazinan-1-yl)-1methyl-1H-indol-2-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-13-carbonytriyl-yl] Petition 870250080967, dated 09 / 09 / 2025, p. 502 / 523 11 / 30 4-chloro-7-[(3 S)-3-{4-[4-({4-[6-(2,4-dioxo-1,3-diazinan-1-yl)-1methyl-1 H-indol-2-yl]piperidin-1-yl}methyl)pip eridin-1-yl]phenyl}piperidin-1-yl]1H-indazole-3-carbonitrile;7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl} methyl)piperidin-1-yl]phenyl}piperin-4-cardin-indoyl-1;1-1- 4-chloro-7-[4-(4-{4-[(4-{2-[(3 R *)-2,6-dioxopiperidin-3-yl]-7methoxy-1-oxo-2,3-di-hydro-1 H-isoindole-5-yl}piperazine- 1-yl)methyl]piperidinyl-1-]piperidin-]piperidin} H-indole-3-carbonitrile; 4-chloro-7-[4-(4-{4-[(4-{2-[(3 S *)-2,6-dioxopiperidin-3-yl]-7methoxy-1-oxo-2,3-di-hydro-1 H-isoindole-5-yl}piperazin- 1-yl)methyl]piperidinyl-1-]piperidin-]piperidin} H-indole-3-carbonitrile; 4-chloro-7-[4-(4-{4-[(4-{2-[(3 R *)-2,6-dioxopiperidine-3-yl]-1-oxo2,3-di-hydro-1 H-isoindol-5-yl}piperazine-1-yl)methyl]piperidin-1yl}H-phenyl-1-indotrilpiperidine-1; 4-chloro-7-[4-(4-{4-[(4-{2-[(3 S *)-2,6-dioxopiperidin-3-yl]-1-oxo2,3-di-hydro-1 H-isoindol-5-yl}piperazin-1-yl)methyl]piperidin-1yl}H-phenyl-1-indotrilpiperidine-1;7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl} methyl)piperidin-1-yl]phenyl}piperi-13-fln-indotriyl-1 4-chloro-7-[(3 R )-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo2,3-di-hydro-1 H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1yl]H-phenyl}ylpiperiladin-1; 7-(4-{4- [4-({1- [2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperidin-4-yl}methyl)piperazine-1-yl]phenyl}piperidin-1-yl-la)-1-4carbonyfluoro- Petition 870250080967, dated 09 / 09 / 2025, p. 503 / 523 12 / 30 7-[(3 5)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1yl]piperidine-1-yl}methyl)piperidine-1-yl]phenyl}piperidine-1-yl]-4-fluoro-1H-indol3-carbonitrile; 7-[(3 5)-3-{4-[4-({4-[2-(2,6-dioxopiperidine-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl} methyl)piperidin-1-yl]phenyl}piperi-13-fln-indotriyl-14;4-chloro-7-[(3 R )-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidine-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl]-1carbonizol; 4-chloro-7-[(3 R )-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidine-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl]-1H-trindole; 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-1 -ylcar}-Hinotril-4-methyl;3-1-1 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro-1Hisoindol-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-1-yl} -4-methyl-1H-trindole; 7-{4-[4-(4-{4-[4-(2,4-dioxo-1,3-diazinan-1 -yl)-1 H-indol-1yl]piperidin-1-yl}butoxy)phenyl]piperidin-1-yl}-4-methyl-1 H-indol-3 -carbonitrile; 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy-3-oxo-2,3-dihydro-1 H-pyrrolo[3,4-c]pyridin-6-yl]piperazine-1-yl}methyl)piperidin-pyridin-1-pyryl-1-1]phenyl H-indol- 3-carbonitrile;7-{4-[4-(4-{4-[2-(2,6-dioxopiperidine-3-yl)-4-methoxy-3-oxo-2,3-dihydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperazine-1-yl}butoxy)phenyl-pyperidine]yl1}4- 1- H-indole-3-carbonitrile; 4-chloro-7-{4-[4-(4-{4-[2-(2,6-dioxopiperidine-3-yl)-4-methoxy-3oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperazine-1yl}butoxy-)H-phenyl-indotril}pyridine; Petition 870250080967, dated 09 / 09 / 2025, p. 504 / 523 13 / 30 7-{4-[4-(4-{4-[4-(2,4-dioxo-1,3-diazinan-1 -yl)-1 H-indole-1yl]piperidine-1-yl}butoxy)phenyl]piperidin-1-yl}-la}-4-carbony-fluoro-1; 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy-3oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridine-6-yl]piperazine-1-yl}methyl-1-phenyrdin-piperidine1- H-indole-3-carbonitrile; 4-chloro-7-[4-(4-{4-[(4-{2-[(3 R *)-2,6-dioxopiperidin-3-yl]-4methoxy-3-oxo-2,3-di-hydro-1 H-pyrrolo[3,4-c]pyridine-6-yl}piperazine-1yl)methyl]piperidin-1-yl}phenyl)piperidin-1-yl]-1H-indole-3-carbonitrile;4-chloro-7-[4-(4-{4-[(4-{2-[(3 S *)-2,6-dioxopiperidin-3-yl]-4methoxy-3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl)piperazine-pyperil}phenyl-methyl] 1-yl]-1 H-indole-3-carbonitrile; 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy-3-oxo-2,3-dihydro-1 H-pyrrolo[3,4-c]pyridine-6-yl]piperazine-1-yl}methyl)piperidine-pyrrole-1-1-f-1]phenyl H-indole-3-carbonitrile; 4-chloro-7-[(3 S)-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperazine-1pheryln}methyl)piperazine -yl]-1 H-indole-3 -carbonitrile; 4-chloro-7-[(3 S)-3-(4-{4-[(4-{2-[(3 R *)-2,6-dioxopiperidine-3-yl]-4methoxy-3-oxo-2,3-di-hydro-1 H-pyrrolo[3,4-c]pyridine-6-yl}piperazine-1yl)methyl]piperidin-1-yl}phenyl)piperidin-1-yl]-1H-indole-3-carbonitrile;4-chloro-7-[(3 S)-3-(4-{4-[(4-{2-[(3 S *)-2,6-dioxopiperidine-3-yl]-4methoxy-3-oxo-2,3-di-hydro-1 H-pyrrolo[3,4-c]pyridine-6-yl}piperazine-1yl)methyl]piperidin-1-yl}phenyl)piperidin-1-yl]-1H-indole-3-carbonitrile; 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo-2,3-dihydro-1 H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1-yl]-2fluorophenyl-1methyl-4-pyridin) H-indole-3-carbonitrile; 7-(4-{4- [4-({4- [4-(2,4-dioxo-1-yl)-1 H-indol-1yl]piperidin-1-yl}methyl)piperidin-1-yl]-2-fluorophenyl} piperidin- 1-yl)-4-tribonil-3H-indole Petition 870250080967, dated 09 / 09 / 2025, p. 505 / 523 14 / 30 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidine-3-yl)-7-methoxy-1,3-dioxo2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1-yl]-2fluorophenyl}piperidine-1-yl)-4-methyl-1 H-indole-3-carbonitrile; 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro-1 Hysoindol-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-1-yl}-4-fluoro-1H-trindole;4-chloro-7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-1 -yl}-1 H-trindole; 4-chloro-7-{4-[4-(4-{4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol1-yl]piperidin- 1-yl}butoxy)phenyl]piperidin-1 -yl}-1 H-indol-3-carbonitrile; 4-chloro-7-[(3 R )-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperazin-1pherydin-1perinyl}methyl)piperazine -yl]-1 H-indole-3 -carbonitrile; 7-{4-[4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1,3-dioxo2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]piperidine-1-yl};-4carbonyl-1 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1,3dioxo-2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1-peridin-1]phenyl}pi H-indole-3-carbonitrile;7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo-2,3di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin- 1-yl-1;H3}-carbonindoyl-methyl 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3dioxo-2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1-peridin-1]phenyl}pi H-indole-3-carbonitrile; 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1yl]phenyl} piperil-1-4-flu-1-yl -carbonytrile; Petition 870250080967, dated 09 / 09 / 2025, p. 506 / 523 15 / 30 4-chloro-7-[(3 5)-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6-fluoro1,3-dioxo-2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1yl]phenyl}piperidine-1-yl]-1 H-indole-3-carbonitrile; 4-chloro-7-[(3 R )-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6-fluoro1,3-dioxo-2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}methyl-methyl-1-1-]piperidin] H-indole-3-carbonitrile;4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxo-2,3di-hydro-1 H-isoindol-5-yl]piperazine-1-yl} methyl)piperidin-1-yl]phenyl}-piperidin-1 Hcar-indoyl) 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxo-2,3-di-hydro1H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-1-yl}-4-methyl-3- H-carbonindol; 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro-1 Hysoindol-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-1-yl}-1 H-indol-3carbonitrile; 7-{4-[4-(4-{4-[4-(2,4-dioxo-1,3-diazinan-1 -yl)-1 H-indol-1yl]piperidin-1-yl}butoxy)phenyl]piperidin-1-yl}-1 H-indol-3-carbonitrile; 7-(4-{4- [4-({4- [4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-1 H-indol-3carbonitrile; 4-chloro-7-(4-{5-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1oxo-2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1-yl]piperidin-1-}yl H-indole-3-carbonitrile;4-chloro-7-(4-{5-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy-3oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridine-6-yl]piperazine-1-yl}methyl-1]piperidine-2-2 H-indole-3 -carbonitrile; 4-chloro-7-(4-{5-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol1-yl]piperidin- 1-yl}methyl)piperidin-1-yl]pyridin-2-yl}piperidin-1-yl)-1 H-indole Petition 870250080967, dated 09 / 09 / 2025, p. 507 / 523 16 / 30 4-chloro-7-(4-{ 6-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol1-yl]piperidin- 1-yl}methyl)piperidin-1-peridin-1-1-pyridazine) H-indol3-carbonitrile; 4-chloro-7-(4-{6-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1-yl]pyridazine-3-yl-ylbonytripyridine-1; 4-chloro-7-[(3 R *)-3-{5-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]pyridin-2-yl}piperidin-carboni-i-tril-yl];3-14-chloro-7-[(3 5 *)-3-{5-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]pyridin-2-yl}piperidin-1-yl]-1Hindol-3-carbonitrila; 4-chloro-7-(4-{5-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol1-yl]piperidin- 1-yl}methyl)piperidin-1-yl]pyrazin-2-yl}piperidin-1-yl)-1H-indol-3carbonitrila; 4-chloro-7-(4-{5-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1-yl]pyrazin-2yl}piperidin-1-yl)-1 H-indol-3-carbonitrila; 7-[4-(4-{4-[(4-{[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1 H-benzimidazol-4-yl]methyl}piperazin-1-yl)methyl]piperidin-1 yl}phenyl)piperidin-1-yl]-4-methyl-1 H-indol-3-carbonitrila; 4-chloro-7-[4-(4-{4-[(4-{[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2oxo-2,3-di-hidro-1 H-benzimidazol-4-yl]methyl}piperazin-1-yl)methyl]piperidin1-yl}phenyl)piperidin-1 -yl]-1 H-indol-3 -carbonitrila;7-[4-(4-{4-[(4-{[[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1 H-benzimidazol-4-yl]methyl}piperazine-1-yl)methyl]piperidin-1yl}phenyl H-3-4-ylfluperidin-[(4-{[1-(2,6-dioxopiperidin-3-yl) -carbonytrile; Petition 870250080967, dated 09 / 09 / 2025, p. 508 / 523 17 / 30 4-chloro-7-(4-{4-[4-({4-[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo2,3-di-hydro-1 H-benzimidazol-4-yl]piperazine-1-yl}methyl)piperidine-1yl]phenyl}piperidine-1-yl)-1 H-indole-3-carbonitrile; 4-chloro-7-[(3 S)-3-(4-{4-[(4-{[1-(2,6-dioxopiperidin-3-yl)-3-methyl2-oxo-2,3-di-hydro-1 H-benzimidazol-4-yl]methyl}piperazine-1yl)methyl-pi-peril}phen-1) H-indole-3-carbonitrile; 7-[(3 S)-3-(4-{4-[(4-{[[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo2,3-di-hydro-1 H-benzimidazole-4-yl]methyl}piperazm-1-yl)methyl]piperidin-ylf]luperidine-1-phenyl H-indole-3 -carbonitrile;4-chloro-7-{4-[4-(4-{[6-(2,6-dioxopiperidin-3-yl)-5,7-dioxo-3,5,6,7tetra-hydropyrrole[3,4-f]isoindole-2(1 H)-yl]methyl}piperidin-1-yl) Hfeml-trindol}pyri-13; 4-chloro-7-{(3 S)-3-[4-(4-{[[6-(2,6-dioxopiperidin-3-yl)-5,7-dioxo3,5,6,7-tetra-hydropyrrole[3,4-f]isoindole-2(1 H)-yl]methyl}piperidin-pi}-1-phenyl-phenyl] H-indazole-3-carbonitrile; 4-chloro-7-{(3 S)-3-[4-(4-{[[6-(2,6-dioxopiperidin-3-yl)-5,7-dioxo3,5,6,7-tetra-hydropyrrole[3,4-f]isoindole-2(1 H)-yl]methyl}piperidin-pi}-1-phenyl-phenyl] H-indole-3-carbonitrile; 7-{(3 R *)-1-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-3 -ylcar}-Hybontril-4-methyl;3-1-1 7-{(3 S*)-1-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-3 -ylcar}-Hybontril-4-methyl;3-1-17-{(3 R *)-1-[3-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-3 -ylcar}-Hybontril-4-methyl;3-1-1 Petition 870250080967, dated 09 / 09 / 2025, p. 509 / 523 18 / 30 7-{(3 S*)-1-[3-(4-{4-[2-(2,6-dioxopiperidine-3-yl)-1-oxo-2,3-dihydro-1 H-isoindole-5-yl]piperazine-1-yl}butoxy-4meth-3phenyl] Hyndol-3-carbonitrile; 7-[(3 R *)-1-{4-[4-({4-[2-(2,6-dioxopiperidine-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl} methyl)piperidin-1-yl]phenyl}piperin-3-4-i-metriyl-1; 7-[(3 S *)-1-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl} methyl)piperidin-1-yl]phenyl}piperin-3-4-indoyl-indoyl-1; 4-chloro-7-(4-{4-[4-({4-[6-(2,4-dioxo-1,3-diazinan-1-yl)-1-methyl1H-indol-2-yl]piperidin- 1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl-la)-1 Carbonitrile4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidine-1carbonyl]phenyl}piperitridin-1;1-indo) 4-chloro-7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy-3oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperazine-1-yl}piperidin-]piperidin-}1-phenyl) H-indole-3-carbonitrile; 4-chloro-7-(4-{4-[4-(2-{4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy-3oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperazine-1-yl-yl}-pyperidin-1)pyridine H-indole-3-carbonitrile; 4-chloro-7-(4-{4-[4-(3-{4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy-3oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridine-6-yl]piperazine-1-yl-peridinyl}propyl-propyl-1)pi H-indole-3-carbonitrile; 7-(4-{4- [4-({4- [5-(2,4-dioxo-1-yl)-1 H-indol-1yl]piperidine-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-4-fluoro-1H-indole;carbon3-indolePetition 870250080967, dated 09 / 09 / 2025, p. 510 / 523 19 / 30 4-chloro-7-(4-{4-[4-({4-[5-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol1-yl]piperidin- 1-yl}methyl)piperidin-1-yl]peridin-1}pyl H-indole-3carbonitrile; 4-chloro-7-[(3 R *)-1-{4- [4-({4- [2-(2,6-dioxopiperidin-3 -yl)-4methoxy-3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperazin-piperin-}piperidin-1}pheperidin-1methyl -yl]-1 H-indole-3 -carbonitrile; 4-chloro-7-[(3 S *)-1-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4methoxy-3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperazin-yl]piperidin-pheridin-methyl) -yl]-1 H-indole-3 -carbonitrile; 4-chloro-7-[(3 R *)-1-{4- [4-({4- [2-(2,6-dioxopiperidin-3 -yl)-1-oxo2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1yl-1-3-phenyl-indoperil] 4-chloro-7-[(3 S *)-1-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo2,3-di-hydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1yl] H-3-3carbonindotripyridine-1-17-{4-[4-(4-{4-[2-(2,6-dioxopiperidine-3-yl)-1-oxo-2,3-di-hydro-1 Hysoindol-5-yl]piperazine-1-yl}butoxy)phenyl]piperazine-1-yl}-4-methyl-1 H-itrindole; 4-chloro-7-[(3 R *)-1-{4-[1-({1- [2-(2,6-dioxopiperidin-3 -yl)-1-oxo2,3-di-hydro-1 H-isoindol-5-yl]piperidin-4-yl}methyl)piperidine-4yl] H-3-carbonyl}ypiperidine-1-1 4-chloro-7-[(3 S *)-1-{4-[1-({1 -[2-(2,6-dioxopiperidin-3-yl)-1-oxo2,3-di-hydro-1 H-isoindol-5-yl]piperidin-4-yl}methyl)piperidin-4yl]H-3-carbonyl-ylpyperidine-1-1 4-chloro-7-[(3 R *)-1-{4-[1-({1- [2-(2,6-dioxopiperidin-3 -yl)-4methoxy-3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridin-6-yl]piperidin-4piperidin-pheridin-methyl) -yl]-1 H-indole-3 -carbonitrile; Petition 870250080967, dated 09 / 09 / 2025, p. 511 / 523 20 / 30 4-chloro-7-[(3 S *)-1-{4-[1-({1-[2-(2,6-dioxopiperidin-3-yl)-4methoxy-3-oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridine-6-yl]piperidine-4yl}methyl)piperidine-4-yl]phenyl}piperidin-3 -yl]-1 H-indole-3 -carbonitrile;4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3dioxo-2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}methyl)piperidine-1carbon-1-3-yldin]H-1-phenyl}piperidine -carbonytrile; 7-[4-(4-{[1-({1-[2-(2,6-dioxopiperidin-3 -yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperidine-4-yl}methyl)piperidin-4-yl]oxy}phenyl)piperidin-carbon-1-fluorol-yl-3-4 4-chloro-7-(4-{4-[4-({4-[5-(2,4-dioxo-1,3-diazinan-1-yl)-7-methyl1H-indol-1 -yl]piperidin- 1-yl}methyl}methyl}methyl}methyl}piperidin-1-yl]phenyl}piperidin-1-bonytriyl-la)-3-1car 4-chloro-7-(4-{4-[4-({4-[6-(2,4-dioxo-1,3-diazinan-1-yl)-1-methyl1H-pyrrolo[3,2-b]pyridine-2-yl]piperidin-1-yl}methyl)piperidin-1yl]H-phenyl-yl}piperiladin-1;1 4-{4-[(1-{4-[(3 S)-1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-3yl]phenyl}piperidin-4-yl)methyl]piperazine-1-yl}- N-(2,6-dioxopiperidin-3-yl)-midate;2fluorobenza4-{4-[(1-{4-[1-(3-cyano-4-fluoro-1 H-indol-7-yl)piperidin-4yl]phenyl}piperidin-4-yl)methyl]piperazine-1-yl}- N-(2,6-dioxopiperidin-3-yl)-2fluorobenzamide; 4-{4-[(1-{4-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4yl]phenyl}piperidin-4-yl)methyl]piperazine-1-yl}- N-(2,6-dioxopiperidin-3-yl)-2fluorobenzamide; 7-[4-(4-{[4-({1-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperidin-4-yl}methyl)piperazine-1-yl]methyl}phenyl)piperidin-carbon-1yluorola]-1-4-4 Petition 870250080967, dated 09 / 09 / 2025, p. 512 / 523 21 / 30 4-chloro-7-(4-{ 6-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol1-yl]piperidin- 1-yl}methyl)piperidin-1-yl-yl]ylpyridin-1-3 H-indole-3carbonitrile; 4-chloro-7-(4-{6-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)piperidin-1-yl]pyridin-3yl bony}piperiladin-3-1-1-14-chloro-7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl}piperidin-1 -yl)phenyl]piperidin-1-bonitril-la}-1 car 4-chloro-7-[4-(4-{4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1yl][ 1,4'-bipiperidine] -1'-yl}phenyl)piperidin-1-yl]-1 H-indol-3; -carbonitrile 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1oxo-2,3-di-hydro-1H-isoindole-5 -yl]piperazine-1-yl}methyl)piperidine-1yl]phenyl}piperidin-1-yl)-1-methyl-1H-indole-3-carbonitrile; 4-chloro-7-(4-{3-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl} methyl)piperidin-1-yl]phenyl}piperidin H-13-indotril)-1 4-chloro-7-[(3 X)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1 -yl)-1 H-indol-1 -yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperil-1-H-1-indoyl]4-chloro-7-[(3 X *)-3-{6-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]pyridin-3-yl}piperidin-carboni-i-tril-yl];3-1 4-chloro-7-[(3 R *)-3-{6-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]pyridin-3-yl}piperidin-car Hindotril-la]-3-1 4-chloro-7-[(2 X *)-2-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidine-1-yl}methyl)piperidin-1-yl]phenyl}morpholin-4-yl]-1H-indole; Petition 870250080967, dated 09 / 09 / 2025, p. 513 / 523 22 / 30 4-chloro-7-[(2 R *)-2-{4- [4-({4- [4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-}mor]-folin-4-phenyl] H-indole-3carbonitrile; 4-chloro-7-[(2 X *)-2-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}morpholin-4-yl]-1 H-carbonitrizole;4-chloro-7-[(2 R *)-2-{4- [4-({4- [4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}morpholin-4-yl]-1 H-indazol3-carbonitrila; 4-chloro-7-[(3 R *)-3-{6-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]pyridazin-3-yl}piperidin-1-yl]-1 Hindol-3-carbonitrila; 4-chloro-7-[(3 X *)-3-{6-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)piperidin-1-yl]pyridazin-3-yl}piperidin-1-yl]-1 Hindol-3-carbonitrila; 4-chloro-7-(4-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-2-methyl1H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-1 Hindol-3-carbonitrila; 4-chloro-7-(4-{2-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1-yl]pyrimidin-5yl}piperidin-1-yl)-1 H-indol-3-carbonitrila;4-chloro-7-(4-{2-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol1-yl]piperidin- 1-yl}methyl)piperidin-1-yl]pyrimidine-5-yl}piperidin-1-yl-la)-1 Carbonitrile 7-(4-{4-[(2 R )-2-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)morpholin-4-yl]phenyl}piperidin-carbonirol-13-yl)-4 Petition 870250080967, dated 09 / 09 / 2025, p. 514 / 523 23 / 30 4-chloro-7-(4-{4-[(2 R )-2-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo2,3-di-hydro-1 H-isoindole-5-yl]piperazin-din-1-morphenyl-yl}-methyl] H-indole-3-carbonitrile; 7-(4-{4-[7-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindol-5-yl]piperazine-1-yl}methyl)-2-yl-azaspiro[3.5]nonan-2-peril-14-flu-phenyl} pi H-indole-3 -carbonitrile; 4-chloro-7-(4-{4-[7-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl}methyl)-2-azaspiro[3.5]nonanyl-1}piperidin-2yl] H-indole-3-carbonitrile;4-chloro-7-[(3 S)-3-{4-[7-({4-[2-(2,6-dioxopiperidm-3-yl)-1-oxo2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1-yl}methyl)-2-azaspirophenynyl-1yl}-2.5]no H-indole-3-carbonitrile; 4-chloro-7-[(3 5)-3-{4-[7-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 Hindol-1-yl]piperidin-1-yl}methyl)-2-azaspiro[3.5]nonan-2-peridin H-1]phenyl]pyl -carbonytrile; 4-chloro-7-[(3 R )-3-{4-[4-({4-[6-(2,4-dioxo-1,3-diazinan-1-yl)-1methyl-1H-indol-2-yl]piperidine-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-H-1carbonytrila-yl]1 7-[(3 5)-3-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl} methyl)piperidin-1-yl]phenyl}piperi-13-14-inda-fluyl-carbon]- 7-[(3 5)-3-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1yl]piperidine-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl]-4-carbonyluoro-3;1H7-(4-{4-[7-({4- [4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1yl]piperidin-1-yl}methyl)-2-azaspiro[3.5]carbon-2-yl]phenyl}piperidin-1-ibonirol-l-3-4fluf Petition 870250080967, dated 09 / 09 / 2025, p. 515 / 523 24 / 30 4-chloro-7-[(3 R )-3-{4-[4-({4-[6-(2,4-dioxo- 1,3-diazinan-1 -yl)-5fluoro-1 -methyl-1 H-indol-2-yl]piperidin}methyl-1) -piperidin-methyl-1) il]phenyl}piperidine-1-yl]-1 H-indole-3-carbonitrile; 4-chloro-7-[(3 5)-3-{4-[4-({4-[6-(2,4-dioxo-1,3-diazinan-1 -yl)-5fluoro-1 -methyl-1 H-indol-2-yl]piperidine-1 -yl}methyl)piperidinylpi]peri-1-1]phenyl H-indole-3-carbonitrile; 4-chloro-7-[(3 R )-3-{4-[4-({4-[6-(2,4-dioxo- 1,3-diazinan-1 -yl)-5fluoro-1 -methyl-1 H-indole-2-yl]piperidine-1 -yl}methyl)piperidinylpi]peri-1-1]phenyl H-indazole-3-carbonitrile; 4-chloro-7-[(3 5)-3-{4-[4-({4-[6-(2,4-dioxo-1,3-diazinan-1 -yl)-5fluoro-1 -methyl-1 H-indol-2-yl]piperidine-1 -yl}methyl)piperidinylpi]peri-1-1]phenyl H-indazole-3-carbonitrile;7-(4-{4- [4-({4- [6-(2,4-dioxo-1,3-diazinan-1-yl)-1-methyl-1 H-indol2-yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-4-fluorozol-3;1-Hinda 7-(4-{4- [4-({4- [4-(2,4-dioxo-1,3-diazinan-1-yl)-2-methyl-1 H-indol1-yl]piperidin- 1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1 -yl)-car Hiboni-trifluoro;-1-1 4-chloro-7-(4-{4-[7-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol1-yl]piperidin- 1-yl}methyl)-2-azaspiro[3.5]nonan-2-yl]phenyl phenyl}tril-piperidin-1 4-chloro-7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy-3oxo-2,3-di-hydro-1 H-pyrrole[3,4-c]pyridine-6-yl]piperazine-1-yl}methyl-1-phenyrdin-piperidine1- H-indazole-3 -carbonitrile; 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-4-methoxy-3-oxo-2,3-dihydro-1 H-pyrrole[3,4-c]pyridine-6-yl]piperazine-1-yl}methyl)piperidinel gold-1-1-4-f-phenyl]phenyl H-indazole-3-carbonitrile;Petition 870250080967, dated 09 / 09 / 2025, p. 516 / 523 25 / 30 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro1H-isoindole-5-yl]piperazine-1-yl}methyl)piperidin-1lu-4-p}l-pyridin-yl]yl H-indazole-3-carbonitrile; 4-chloro-7-(4-{4-[4-({4-[4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol1-yl]piperidin- 1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1 -yl)-1 H-indatrizol; 7-(4-{4- [4-({4- [4-(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1yl]piperidin-1-yl}methyl)piperidin-1-yl]phenyl}piperidin-1-yl)-4-fluoro-1Hindazotrila; -3 7-{4-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo-2,3-dihydro-1 H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]piperidin-1 -yl}-4-carbonethyl-1; 7-(4-{4-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-7-methoxy-1-oxo-2,3-dihydro-1 H-isoindol-5-yl]piperazine-1-yl} methyl)piperidin-1-yl]phenyl}piperin-3-cardin-methyl-1;1)-7-{(3 5 *)-3-[4-(4-{4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]pyrrolidin-1-yl-;3-Hicarbonindotril 7-{(3 R *)-3-[4-(4-{4-[2-(2,6-dioxopiperidine-3-yl)-1-oxo-2,3-dihydro-1H-isoindole-5-yl]piperazine-1-yl}butoxy)phenyl]pyrrolidin-1-yl}-Hybonindol-4-methyl- N-[1-(4-chloro-3-cyano-1 H-indazol-7-yl)piperidin-4-yl]-4-[4-({4-[4(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1 -yl]piperidin- 1-yl}methyl;1benzamide-fluoride-benzamide-fluoride N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidine-4-yl]-4-[4-({4-[5(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1 -yl]piperidin- 1-yl}methyl;1methyl-fluor]benzamide-fluoride Petition 870250080967, dated 09 / 09 / 2025, p. 517 / 523 26 / 30 N-[1-(4-chloro-3-cyano-1~{H}-indol-7-yl)-4-piperidyl]-4-[4-[[4-[4[(2,6-dioxo-3-piperidyl)carbamoyl]-3-fluoro-phenyl]piperazine-1-yl]perimithyl]-1pi-benzeneN-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-(4-{[6-(2,6dioxopiperidin-3-yl)-5,7-dioxo-3,5,6,7-tetra-hydropyrrolo[3,4-f]isoindol-2(1 H)yl]methyl}piperidin-1-yl)-2-fluorobenzamida; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4-[6(2,4-dioxo-1,3-diazinan-1-yl)-5-fluoro-1-methyl-1 H-indol-2-yl]piperidin-1yl}methyl)piperidin-1-yl]-2-fluorobenzamida; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4-[1(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-di-hidro-1 H-benzimidazol-4yl]piperazin-1 -yl}methyl)piperidin-1-yl]-2-fluorobenzamida; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4-[6(2,4-dioxo-1,3-diazinan-1-yl)-1-methyl-1 H-indol-2-yl]piperidin-1yl}methyl)piperidin-1-yl] -2-fluorobenzamida; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4-[2(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hidro-1H-isoindol-5-yl]piperazin-1yl}methyl)piperidin-1-yl] -2-fluorobenzamide;N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4- [4(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1 -yl]piperidin- 1-yl}methyl;1fluor]benzamide-fluoride N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4-[2(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo-2,3-di-hydro-1H-isoindol-1piperazine-5yl] -yl}methyl)piperidine-1-yl]-2-fluorobenzamide; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-2-cyano-4-[4({4-[4-(2,4-dioxo-1,3-diazinan- 1-yl)-1 H-indol-1-yl]piperidin-1be lyrene-methyl}methyl-pi] Petition 870250080967, dated 09 / 09 / 2025, p. 518 / 523 27 / 30 N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4- [4(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indolperidin -]yl 1-yl}methyl)piperidine-1yl]-2-fluoro-6-methylbenzamide; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4- [4(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1 -yl]piperidin- 1-yl}methylbenzamide]pinzamidine-N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-3-cyano-4-[4({4-[4-(2,4-dioxo-1,3-diazinan- 1-yl)-1 H-indol-1-yl]piperidin-1 yl}methyl)piperidin-1-yl]benzamida; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-5-(4-{4-[2(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo-2,3-di-hidro-1 H-isoindol-5yl]piperazin-1 -yl}piperidin-1-yl)pyridine-2-carboxamide; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-5-[4-({4-[4(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1yl]pyridine-2-carboxamide; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-5-[4-({4-[2(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro-1H-isoindol-5-yl]piperazin-1yl}methyl)piperidin-1-yl]pyridine-2 -carboxamide; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-5-[4-({4-[2(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo-2,3-di-hidro-1H-isoindol-5yl]piperazin-1 -yl}methyl)piperidin-1-yl]pyridine-2-carboxamide;N-[1-(4-chloro-3-cyano-1 H-indazol-7-yl)piperidin-4-yl]-5-[4-({4-[4(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1 -yl]piperidin- 1-yl}methyl)carpyperidine-1; N-[1-(3-cyano-4-methyl-1 H-indol-7-yl)piperidin-4-yl]-5-[4-({4-[2(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo-2,3-di-hydro-1H-isoindol-5yl] -yl}methyl)piperidine-1-yl]pyridine-2-carboxamide; Petition 870250080967, dated 09 / 09 / 2025, p. 519 / 523 28 / 30 N-[1-(3-cyano-4-methyl-1 H-indol-7-yl)piperidin-4-yl]-5-[4-({4-[2(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-di-hydro-1 H-isoindole-5-yl]piperazine-1yl}methyl)piperidine-1-yl]pyridine-2 -carboxamide; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4- [4(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1 -yl]piperidin- 1-yl}methyl1;)piperinzamidine- N-[4-(4-chloro-3-cyano-1 H-indol-7-yl)cyclo-hexyl]-4-[4-({4-[4-(2,4dioxo-1,3-diazinan-1-yl)-1 H-indol- 1-yl]piperidin-1-yl}methyl}oro)piperinzamidane2;1-luN-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4-[4(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1yl]-2,6-difluorobenzamida; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-5-[4-({4-[4(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1yl]pyrazine-2-carboxamida; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-5-[4-({4-[4(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1yl]pyrimidine-2-carboxamide; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-4-[4-({4-[4(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1yl]-2-methylbenzamide; N-[1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-4-yl]-6-[4-({4-[4(2,4-dioxo-1,3-diazinan-1-yl)-1 H-indol-1 -yl]piperidin- 1-yl}methyl)piperidin-1yl]pyridazine-3-carboxamide;N-[(3R*)-1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-3-yl]-5-[4({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5yl]piperazin-1 -yl}methyl)piperidin-1-yl]pyridine-2-carboxamide; and Petition 870250080967, of 09 / 09 / 2025, p. 520 / 523 29 / 30 N-[(3 S *)-1-(4-chloro-3-cyano-1 H-indol-7-yl)piperidin-3-yl]-5-[4({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1 H-isoindol-5yl]piperazin-1 -yl}methyl)piperidin-1-yl]pyridine-2-carboxamide; or pharmaceutically acceptable salts thereof; 21. Pharmaceutical composition, characterized in that it comprises a compound of formula (I) or a PROTAC of formula (Ia), or a pharmaceutically acceptable salt thereof, as defined in one of claims 1 to 20, in association with a pharmaceutically acceptable excipient.

22. Compound of formula (I) or PROTAC of formula (Ia), or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 20, characterized in that it is intended for use in a method of treating the human or animal body by therapy.

23. Compound of formula (I) or PROTAC of formula (Ia), or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 20, characterized in that it is intended for use as an anti-invasive agent in the containment and / or treatment of solid tumor disease.

24. Use of a compound of formula (I) or a PROTAC of formula (Ia), or a pharmaceutically acceptable salt thereof, as defined in any of claims 1 to 20, characterized in that it is intended for the manufacture of a medicament for use as an anti-invasive agent in the containment and / or treatment of solid tumor disease.

25. Method for producing an anti-invasive effect by restraining and / or treating solid tumor disease in a warm-blooded animal, such as a human, in need of such an effect, characterized in that it comprises administering to said animal an effective amount of a compound of formula (I) or a PROTAC of formula Petition 870250080967, dated 09 / 09 / 2025, page 521 / 523 30 / 30 (Ia), or a pharmaceutically acceptable salt thereof, as defined in any of claims 1 to 20.