Substituted pyrimidine compounds as IRAK-m degraders

Abstract

The present invention is directed to compound of formula (I), stereoisomer thereof or pharmaceutically acceptable salts thereof, which are useful as IRAK-M degraders, processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment or prevention of various diseases, conditions and / or disorders mediated by IRAK-M.

Description

[0001] SUBSTITUTED PYRIMIDINE COMPOUNDS AS IRAK-M DEGRADERS

[0002] REEATED APPEICATIONS

[0003] This application claims the benefit of an Indian Provisional Application No. 202321049381 filed on July 21, 2023 and an Indian Provisional Application No 202421002663 filed on January 13, 2024; the contents of which are hereby incorporated by reference in their entirety.

[0004] TECHNICAL FIELD

[0005] The present patent application is directed to substituted pyrimidine compounds which are useful as IRAK-M degraders, processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment or prevention of various diseases, conditions and / or disorders mediated by IRAK-M.

[0006] BACKGROUND OF THE INVENTION

[0007] IRAK3 (interleukin- 1 receptor-associated kinase 3, also known as IRAK-M) is a class- 1 pseudokinase member of the IRAK family. The four different IRAK-like molecules have been identified: two active kinases, IRAK-1 and IRAK-4, and two pseudo kinases, IRAK-2 and IRAK-M. IRAK-M is found mainly in cells of monomyeloic origin and is, therefore, designated IRAK-M. The first article published in Journal of Biological Chemistry, 1999, 274(27), 19403-19410 related to IRAK-M as a Novel Member of the Pelle / Interleukin- 1 Receptor- associated Kinase (IRAK) Family.

[0008] Members of this family are essential components of the Toll / IL-R immune signal transduction pathways. This protein is primarily expressed in monocytes and macrophages and functions as a negative regulator of TLR signaling. IRAK-M as a negative regulator of innate immune signaling and mutations in IRAK-M are associated with asthma and cancer. Alternate splicing results in multiple transcript variants. IRAK-M is induced by TLR stimulation and required for endotoxin tolerance, indicating that IRAK-M is a key component of a feedback regulatory system of innate immunity. IRAK-M therefore plays a critical role in the maintenance of homeostasis of the innate immune system.

[0009] The first structure of the IRAK-M pseudokinase domain reveals that IRAK-M to be in a pseudoactive conformation and to form a novel head to-head dimer. Asthma-associated mutations and structural analyses suggest new mechanistic models on how IRAK-M might function as a negative regulator of innate immunity (Lange et al. Structure, 2021, 29, 238- The tumor microenvironments of cancers are immunosuppressive, and an IRAK-M knockout (KO) demonstrated enhanced function of myeloid cells to promote antitumor responses. TLRs, TGFβ, CD44, and HIF1α / hypoxia are all known inducers of IRAK-M expression, and IRAK-M polymorphs in human have been associated with a subset of asthma, sepsis, and sensitivity to anti-TNFα therapy in rheumatoid arthritis. Monocytes cocultured with tumor cells show decreased TNF-α, IL-12, and IRAK1 expression but an increase in IRAK-M expression. Conversely, dendritic cells (DCs) from IRAK-M− / − mice showed enhanced production of pro-inflammatory cytokine production relative to wild-type (WT) DCs, which induces a T-cell response and results in tumor growth inhibition, making IRAK-M degradation an attractive strategy in immune-oncology (Rowley, Brown et al. ACS Chem Biol, 2022, 17, 1315-1320). International patent publications WO / 2021 / 020585; WO / 2021 / 020586; WO / 2017 / 211924; WO / 2018 / 033556; discloses compounds as degrading target proteins of our interest and the treatment of disorders mediated by the said target proteins. J. Med. Chem. 2020, 63, 10460-10473 and ACS Chem. Biol.2022, 17;17(6):1315-1320; discloses heterocyclic compounds as selective IRAK-M degraders. The major challenge currently faced in the field is to provide the compounds inducing the degradation of IRAK-M thereby preventing the disease, disorder associated with IRAK-M such as cancer, asthma, inflammatory bone disease, inflammatory lung disease, idiopathic pulmonary fibrosis, inflammatory bowel disease, infectious diseases, and the like. Being a pseudo kinase, molecules binding to active site of RAK-M are less likely to produce any functional effect, and to provide the effective solution to this problem, the inventors of the present invention pursued an IRAK-M degradation approach using proteolysis-targeting chimeras (PROTACs)to identify potent IRAK-M degraders. SUMMARY OF THE INVENTION In yet another aspect, the present invention relates to compound of formula (I)

[0010] or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein, X1is selected from N and CH; X2is selected from N and CH; R1is selected from hydrogen, C1-8alkyl, hydroxylC1-8alkyl, haloC1-8alkyl; R2is selected from -C(O)2Rxand 5-14 membered heteroaryl ring; wherein 5-14 membered heteroaryl is unsubsituted or substituted with one or more substituents selected from C1-8alkyl, haloC1-8alkyl or hydroxyC1-8alkyl; Rxis selected from hydrogen and C1-8alkyl; Rpis selected from hydrogen and C1-8alkyl; Rqis selected from hydrogen and C1-8alkyl; each occurrence of Reis independently selected from halogen, C1-8alkyl, hydroxylC1- 8alkyl and haloC1-8alkyl; each occurrence of R3is independently selected from halogen, C1-8alkyl, hydroxyl, hydroxylC1-8alkyl and haloC1-8alkyl; each occurrence of R4is independently selected from halogen, C1-8alkyl, hydroxylC1- 8alkyl and haloC1-8alkyl; x and y independently represent the point of attachment; Z is absent or is selected from –O-, -C(O)-, -NH- and –S-; ring D is selected from 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; wherein 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl are each unsubstituted or substituted with one or more substituents selected from halogen, hydroxyl or oxo; ring E is selected from 5 to 12 membered spiroheterocyclyl ring, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; wherein 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl are each unsubstituted or substituted with one or more substituents selected from halogen, hydroxyl, oxo or C1-8alkoxy; ring P is selected from C6-14aryl, C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; wherein C6-14aryl, C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl are each unsubstituted or substituted with one or more substituents selected from halogen, hydroxyl or oxo; W1is absent or is selected from –C(O)–, –CONH– and –CH2–; W2is absent or is selected from –C(O)–, –CONH– and –CH2–; W3is absent or is selected from 3 to 15 membered heterocyclyl ring, –O–, –N-CH3–, – C(O)–, –CONH, –(CRmRn)f-C(O)–, –(CRiRj)e–, –O-(CH2)l– and –C≡C–; W4is absent or –O–; ring F is 3 to 15 membered heterocyclyl ring; ring G is 3 to 15 membered heterocyclyl ring; Y is absent or is selected from –O–, –C(O)–, –NH– and –S–; ring H is selected from C3-12cycloalkyl and 3 to 15 membered heterocyclyl ring; T1is absent or is selected from –C(O)– and–CH2–; T2is absent or is selected from –C(O)– and –(CH2)i–; . ring J is selected from C3-12cycloalkyl and 3 to 15 membered heterocyclyl ring; ring K is selected from 3 to 15 membered heterocyclyl ring and 5 to 12 membered spiroheterocyclyl ring; ring S is selected from C3-12cycloalkyl and 3 to 15 membered heterocyclyl ring; ring O is selected from C3-12cycloalkyl and 3 to 15 membered heterocyclyl ring; Ra, Rb, Rc, Rd, Ri, Rj, Rmand Rnare independently selected from selected from hydrogen, halogen, hydroxyl, C1-8alkyl, hydroxylC1-8alkyl and haloC1-8alkyl; Rcand Rd, together with the carbon atom to which they are attached to form C3-12cycloalkyl ring; wherein C3-12cycloalkyl ring is unsubstitued or substituted with one or more substituents selected from halogen, hydroxyl, oxo, C1-8alkyl, haloC1-8alkyl, hydroxyC1-8alkyl and haloC1-8alkyl; Rband Rc, together with the carbon atom to which they are attached to form C3-12cycloalkyl ring; wherein C3-12 cycloalkyl ring is unsubstitued or substituted with one or more substituents selected from halogen, hydroxyl, oxo, C1-8alkyl, haloC1-8alkyl, hydroxyC1-8alkyl and haloC1-8alkyl; ‘m’ is 0, 1 or 2; ‘n’ is 0, 1 or 2; ‘h’ is 0, 1 or 2; ‘t’ is 0, 1, 2, 3, 4 or 5; ‘r’ is 0, 1, 2, 3 or 4; ‘f’ is 1, 2 or 3; ‘e’ is 1, 2, 3, 4 or 5; ‘l’ is 0, 1, 2, 3 or 4; ‘j’ is 0, 1 or 2; ‘g’ is 1, 2 or 3; ‘s’ is 0, 1, 2, 3, 4, 5, 6, 7, 8 or 9; ‘i’ is 1, 2 or 3; ‘d’ is 1, 2, 3, 4 or 5; and ‘a’ is 1, 2, 3, 4 or 5; Q is the group is selected from E3 ubiquitin ligase binding moiety, selected from CLM (Cereblon E3 ubiquitin ligase) and VHL (Von Hippel-Lindau E3 ubiquitin ligase); wherein CLM is selected from , X3is selected from CH, N or O; L2is absent or is selected from -O-, -C(O)-, -CONH-and –NRs; ring U is selected from C6-14aryl, C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; each occurrence of R5is independently selected from halogen, hydroxyl, oxo, C1-8alkyl, haloC1-8alkyl and hydroxyC1-8alkyl; R6is selected from hydrogen, halogen, hydroxyl, C1-8alkyl, C1-8alkoxy, haloC1-8alkyl, haloC1-8alkoxy, hydroxyC1-8alkyl and C(O)C1-8alkyl; each occurrence of R7is selected from halogen, hydroxyl, C1-8alkyl, hydroxyC1-8alkyl and haloC1-8alkyl; R8is selected from hydrogen, halogen, hydroxyl, C1-8alkyl, hydroxyC1-8alkyl and haloC1-8alkyl; each occurrence of R9is selected from halogen, hydroxyl, C1-8alkyl, C1-8alkoxy, haloC1-8alkyl, haloC1-8alkoxy and hydroxyC1-8alkyl; R10and R11is independently selected from hydrogen, C1-8alkyl, haloC1-8alkyl and hydroxyC1-8alkyl; R10and R11, together with the nitrogen atom to which they are attached, form a 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; wherein 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring are each unsubstitued or substituted with one or more substituents selected from halogen, hydroxyl, oxo, C1-8alkyl, haloC1-8alkyl, hydroxyC1-8alkyl and haloC1-8alkyl; Rsis selected from hydrogen and C1-8alkyl; Ryis selected from halogen, hydroxyl, C1-8alkyl, haloC1-8alkyl and hydroxyC1-8alkyl; Rzis selected from hydrogen, C1-8alkyl, hydroxyC1-8alkyl and haloC1-8alkyl; ‘p’ is 0, 1, 2 or 3; ‘q’ is 0, 1, 2 or 3; ‘b’ is 0, 1 or 2 and ‘k’ is 0, 1, 2, 3, 4 or 5. In another aspect, the present invention provides a pharmaceutical composition comprising a compound of formula (I) as described herein and a pharmaceutically acceptable excipient. In another aspect, the present invention provides a method of treating or preventing from a disease, disorder or condition mediated by IRAK-3 in a subject comprising administering the subject in need thereof an effective amount of a compound of formula (I) as described herein. DETAILED DESCRIPTION OF THE INVENTION The compounds of formula (I) may involve one or more embodiments. Embodiments of formula (I) include compound of formula (II) and (III) as described hereinafter. It is to be understood that the embodiments below are illustrative of the present invention and are not intended to limit the claims to the specific embodiments exemplified. It is also to be understood that the embodiments defined herein may be used independently or in conjunction with any definition, any other embodiment defined herein. Thus the invention contemplates all possible combinations and permutations of the various independently described embodiments. For example, the invention provides compounds of formula (I) as defined above wherein R1is hydrogen or methyl (according to one embodiment defined below) and ‘m’ is 0 (according to another embodiment defined below). According to one embodiment, specifically provided are compounds of formula (I), in which R1is hydrogen or C1-8alkyl. According to another embodiment, specifically provided are compounds of formula (I), in which R1is hydrogen or methyl. According to yet another embodiment, specifically provided are compounds of formula (I), in which R2is -C(O)2Rxor 5-14 membered heteroaryl ring which is unsubstituted or substituted with C1-8alkyl. In this embodiment Rxis hydrogen or C1-8alkyl. According to yet another embodiment, specifically provided are compounds of formula (I), in which R2is -C(O)2Rxor 1,3,4-oxadiazol-2-yl which is unsubstituted or substituted with methyl. In this embodiment Rxis hydrogen, ethyl or isopropyl. According to yet another embodiment, specifically provided are compounds of formula (I), in which R2is -COOH, -C(O)2CH2CH3, -C(O)2CH(CH3)2, 1,3,4-oxadiazol-2-yl or 5- methyl-1,3,4-oxadiazol-2-yl. According to yet another embodiment, specifically provided are compounds of formula (I), in which X1is N. According to yet another embodiment, specifically provided are compounds of formula (I), in which X2is N or CH. According to yet another embodiment, specifically provided are compounds of formula (I), in which Rqis hydrogen. According to yet another embodiment, specifically provided are compounds of formula (I), in which Reis C1-8alkyl. According to yet another embodiment, specifically provided are compounds of formula (I), in which Reis methyl. According to yet another embodiment, specifically provided are compounds of formula (I), in which ‘h’ is 1. According to yet another embodiment, specifically provided are compounds of formula (I), in which Rpis hydrogen. According to yet another embodiment, specifically provided are compounds of formula (I), in which ‘m’ is 0. According to yet another embodiment, specifically provided are compounds of formula (I), in which ‘n’ is 0. According to yet another embodiment, specifically provided are compounds of formula (I), in which L1is wherein the Z, ring D, ring E, t, r, x, and y are as described in compound of formula (I). In one embodiment, Z is absent or -C(O)-. In one embodiment, ring D is 3 to 15 membered heterocyclyl ring. In one embodiment, ring E is 3 to 15 membered heterocyclyl ring. In one embodiment ‘t’ is 2, 3 or 4 and ‘r’ is 1, 2 or 3. According to yet another embodiment, specifically provided are compounds of formula (I), in which wherein Z is absent or -C(O)-; ring D is 3 to 15 membered heterocyclyl ring; ring E is 3 to 15 membered heterocyclyl ring; ‘t’ is 2, 3 or 4 and ‘r’ is 1, 2 or 3. According to yet another embodiment, specifically provided are compounds of formula (I), in which wherein Z is absent or -C(O)-; ring D is piperidinyl; ring E is piperazinyl; ‘t’ is 2, 3 or 4 and ‘r’ is 1, 2, or 3. According to yet another embodiment, specifically provided are compounds of formula (I), wherein L1 which is selected from , ,

[0011] . According to yet another embodiment, specifically provided are compounds of formula (I), in which wherein x, y, W1, ring P, W2, ring D, W3, ring E, W4, Ri, RjRm, Rn, ‘f’ ‘e’ and ‘l’ are as defined in compound of formula (I). In one embodiment, W1is –C(O)–, In one embodiment, W1is –CH2–. In one embodiment, ring P is C3-12 cycloalkyl ring, C6-14aryl or 3 to 15 membered heterocyclyl ring. In one embodiment, ring P is C3-12cycloalkyl ring. In one embodiment, ring P is C3-10 cycloalkyl ring. In one embodiment, ring P is C3-6 cycloalkyl ring. In one embodiment, W2is –C(O)–, –CONH– or –CH2-. In one embodiment, W2is – C(O)– or –CONH–. In one embodiment, ring D is 3 to 15 membered heterocyclyl ring which is unsubstituted or substituted with one or more substituents selected from halogen or hydroxyl or 5-14 membered heteroaryl ring. In one embodiment, ring D is 3 to 10 membered heterocyclyl ring. In one embodiment, ring D is 5 to 6 membered heterocyclyl ring. In one embodiment, W3is absent. In one embodiment, W3is 3 to 15 membered heterocyclyl ring. In an embodiment, W3is 3 to 10 membered heterocyclyl ring. In one embodiment, W3is 5 to 6 membered heterocyclyl ring. In one embodiment, (CH2)l or –C≡C–. In one embodiment, ring E is 3 to 15 membered heterocyclyl ring which is unsubstituted or substituted with one or more substituents selected from halogen, hydroxyl, oxo or C1-8alkoxy. In one embodiment, ring E is 5-14 membered heteroaryl ring. In one embodiment, ring E is 5 to 12 membered spiroheterocyclyl ring. In one embodiment, Riand Rjare hydrogen or halogen. In one embodiment, Rmand Rnare hydrogen. In one embodiment, ‘f’ is 1 or 2; ‘e’ is 1, 2, 3 or 4, ‘l’ is 2 W4is absent or –O–. According to yet another embodiment, specifically provided are compounds of formula (I), in which wherein W1is –C(O)– or –CH2–; ring P is C3-12cycloalkyl ring, C6-14aryl or 3 to 15 membered heterocyclyl ring; W2is –C(O)–, –CONH– or –CH2-; ring D is 3 to 15 membered heterocyclyl ring which is unsubstituted or substituted with one or more substituents selected from halogen or hydroxyl or 5-14 membered heteroaryl ring; W3is absent or is selected from 3 to 15 membered heterocyclyl ring, –O–, –N-CH3–, – C(O)–, -(CRmRn)f-C(O)-, -(CRiRj)e-, -O-(CH2)l and –C≡C–; ring E is 3 to 15 membered heterocyclyl ring which is unsubstituted or substituted with one or more substituents selected from halogen, hydroxyl, oxo or C1-8alkoxy; Riand Rjare hydrogen or halogen; Rmand Rnare hydrogen; ‘f’ is 1 or 2; ‘e’ is 1, 2, 3 or 4; ‘l’ is 2; and W4is absent or –O–. According to yet another embodiment, specifically provided are compounds of formula (I), in which wherein W1is –C(O)– or –CH2-; ring P is cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentyl, bicyclo[2.2.2]octyl, phenyl or piperidinyl; W2is –C(O)–, –CONH– or –CH2–; ring D is azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl or pyrazolyl which is unsubstituted or substituted with fluoro or hydroxyl; W3is absent or is selected from pyrrolidinyl, piperidinyl, –O–, –N-CH3–, –C(O)–, - (CH2)2-C(O)-, -CF2-C(O)-, -(CH2)e-, –O-(CH2)2– and –C≡C–; ring E is pyrrolidinyl, 2,3-dihydro-pyrrole, piperidinyl, piperazinyl, diazepanyl, 3,8- diazabicyclo[3.2.1]octan-8-yl or 2,5-diazabicyclo[2.2.1]heptan-2-yl which is unsubstituted or substituted with fluoro, hydroxyl, oxo or C1-8alkoxy or pyrazolyl, 2,6-diazaspiro[3.3]heptan- 2-yl, diazaspiro[3.5]nonan-2-yl, 2,7-diazaspiro[3.5]nonan-7-yl, 2,7-diazaspiro[4.4]nonan-2- yl; ‘f’ is 1 or 2; ‘e’ is 1, 2, 3 or 4; ‘l’ is 2; and W4is absent or –O–. According to yet another embodiment, specifically provided are compounds of formula (I), in ,

[0012] . According to yet another embodiment, specifically provided are compounds of formula (I), in which L1is ; wherein x, y, Ra, Rb, Rc, Rd, ring F, ring G, j and g are as defined in compound of formula (I). In one embodiment, Raand Rbare independently selected from hydrogen or C1-8alkyl. In one embodiment, Raand Rbare independently represents hydrogen. In one embodiment, Rcand Rdare independently selected from hydrogen or C1-8alkyl. In one embodiment, Rcand Rdare joined together with the carbon atom to which they are attached to form C3-12cycloalkyl ring. In one embodiment, Rcand Rd, joined together with the carbon atom to which they are attached to form C3-10 cycloalkyl ring. In one embodiment, Rband Rcare joined together with the carbon atom to which they are attached to form C3-12cycloalkyl ring. In one embodiment, Rband Rc, joined together with the carbon atom to which they are attached to form C3-10 cycloalkyl ring. In one embodiment, ring F is 3 to 15 membered heterocyclyl ring. In one embodiment, ring F is 3 to 10 membered heterocyclyl ring. In one embodiment, ring F is 5 to 6 membered heterocyclyl ring. In one embodiment, ring G is 3 to 15 membered heterocyclyl ring. In one embodiment, ring G is 3 to 10 membered heterocyclyl ring. In one embodiment, ring G is 5 to 6 membered heterocyclyl ring. In one embodiment, ‘j’ is 0 or 1 and ‘g’ is 2. According to yet another embodiment, specifically provided are compounds of formula (I), in which wherein Raand Rbare independently represents methyl; Rcand Rdare independently represents hydrogen; ‘j’ is 0 ring F is piperidinyl ring; ring G is piperazinyl ring; and and ‘g’ is 2. According to yet another embodiment, specifically provided are compounds of formula (I), in which wherein Raand Rbare independently represents hydrogen; Rcand Rdare independently represents methyl; ‘j’ is 0; ring F is piperidinyl ring; ring G is piperazinyl ring; and and ‘g’ is 2. According to yet another embodiment, specifically provided are compounds of formula (I), in which wherein Raand Rbare independently represents hydrogen; Rcand Rdare joined together with the carbon atom attached to form cyclopentyl ring; ‘j’ is 1; ring F is piperidinyl ring; ring G is piperazinyl ring; and and ‘g’ is 2. According to yet another embodiment, specifically provided are compounds of formula (I), in which wherein Rais hydrogen; Rband Rcand are join together with the carbon atom attached to form cyclopropyl, cyclobutyl or cyclohexyl ring; Rdis hydrogen; ring F is piperidinyl; ring G is piperazinyl; ‘j’ is 0; and ‘g’ is 2. According to yet another embodiment, specifically provided are compounds of . According to yet another embodiment, specifically provided are compounds of formula (I), in which L1is wherein x, y, Y, ring H and ‘s’ are as defined in compound of formula (I). In one embodiment, Y is absent or C(O). In one embodiment, ring H is C3-12cycloalkyl ring or 3 to 15 membered heterocyclyl ring. In one embodiment, ‘s’ is 0, 2 or 9. According to yet another embodiment, specifically provided are compounds of formula (I), in which L1is wherein Y is absent or C(O); ring H is cyclohexyl or piperazinyl and ‘s’ is 0, 2 or 9. According to yet another embodiment, specifically provided are compounds of formula . According to yet another embodiment, specifically provided are compounds of formula (I), in which L1is wherein x, y, T1, ring j, T2, ring K, T3and ‘i’ are as defined in compound of formula (I). In one embodiment, T1is -C(O)- or –CH2–, In one embodiment, ring J is C3-12cycloalkyl ring or 3 to 15 membered heterocyclyl ring. In one embodiment, ring J is C3-12cycloalkyl ring. In one embodiment, ring J is C3-10cycloalkyl ring. In one embodiment, ring J is C3-6 cycloalkyl ring. In one embodiment, T2is -C(O)- or –(CH2)i–. In one embodiment, ring K is 3 to 15 membered heterocyclyl ring or 5 to 12 membered spiroheterocyclyl ring. In one embodiment, ring K is 3 to 10 membered heterocyclyl ring. In one embodiment, ring K is 5 to 6 membered heterocyclyl ring. In one embodiment, ‘i’ is 1 or 3. In one embodiment, T3is absent or is selected from . According to yet another embodiment, specifically provided are compounds of formula (I), in which wherein T1is -C(O)- or –CH2–; ring J is cyclohexyl or piperidinyl; T2is -C(O)- or –(CH2)i–; ring K is piperazinyl, piperidinyl, 3,9-diazaspiro[5.5]undecanyl, 2,7- diazaspiro[3.5]nonan-2-yl, 2,9-diazaspiro[5.5]undecan-9-yl, 2,6-diazaspiro[3.3]heptan-2-yl or 2,7-diazaspiro[3.5]nonan-7-yl; ‘i’ is 1 or 3; and T3is absent or is selected from . According to yet another embodiment, specifically provided are compounds of formula (I), in which L1is which is selected from . According to yet another embodiment, specifically provided are compounds of formula (I), in which L1is wherein x, y, ring S and ‘d’ are as defined in compound of formula (I). In one embodiment, ring S is 3 to 15 membered heterocyclyl ring. In one embodiment, ‘d’ is 1, 2 or 3. According to yet another embodiment, specifically provided are compounds of formula (I), in which L1is wherein ring S is pyrrolidine, piperidinyl or piperazinyl; and ‘d’ is 1, 2 or 3. According to yet another embodiment, specifically provided are compounds of formula . According to yet another embodiment, specifically provided are compounds of formula (I), in which L1is wherein x, y and ring O are as defined in compound of formula (I). In one embodiment ring O is C3-12cycloalkyl or 5 to 12 membered spiroheterocyclyl ring. According to yet another embodiment, specifically provided are compounds of formula (I), in which L1is wherein ring O is cyclohexyl or 3- azaspiro[5.5]undecan-9-yl; According to yet another embodiment, specifically provided are compounds of formula . According to yet another embodiment, specifically provided are compounds of formula (I), in which L1is wherein x, y and ‘a’ are as defined in compound of formula (I). According to yet another embodiment, specifically provided are compounds of formula (I), in which . this embodiment ‘a’ is 3 or 4. ccording to yet another embodiment, specifically provided are compounds of formula . According to yet another embodiment, specifically provided are compounds of formula (I), in which L1is ,

[0013] According to yet another embodiment, specifically provided are compounds of formula (I), in which Q is E3 ubiquitin ligase binding moiety. In this embodiment E3 ubiquitin ligase binding moiety is CLM or VHL. According to yet another embodiment, specifically provided are compounds of formula (I), in which Q is CLM. According to yet another embodiment, specifically provided are compounds of formula wherein, ‘b’, ‘k’, Rz., Ry, X3, L2, ring U, R5, Rsare as defined in compound of formula (I). According to yet another embodiment, specifically provided are compounds of formula (I), in which wherein Rzis hydrogen and ‘b’ is 0. According to yet another embodiment, specifically provided are compounds of formula (I), in which . According to yet another embodiment, specifically provided are compounds of formula (I), in which wherein ‘b’ is 0; Rzis hydrogen or C1-8alkyl; X3is CH or N; L2is absent or a group selected from -O-, -C(O)-, -CONH- and –NRs; ring U is C6-14aryl, 3 to 15 membered heterocyclyl ring or 5-14 membered heteroaryl ring; R5is halogen, oxo or C1-8alkyl; Rsis hydrogen or C1-8alkyl; and ‘k’ is 0, 1 or 2. According to yet another embodiment, specifically provided are compounds of formula (I), in which wherein ‘b’ is 0; Rxis hydrogen; Rzis hydrogen or methyl; X3is CH or N; L2is absent or a group selected from -O-, -CO-, -CONH- or -N-CH3; ring U is phenyl, dihydropyridine, pyridine, isoindoline, indazolyl or 2,3-dihydro-1H- benzo[d]imidazol-5-yl; R5is fluoro, oxo or methyl; Rsis hydrogen or methyl and ‘k’ is 0, 1 or 2. According to yet another embodiment, specifically provided are compounds of formula (I), in which which is selected from , . According to yet another embodiment, specifically provided are compounds of formula . According to yet another embodiment, specifically provided are compounds of formula (I), in which Q is VHL which is represented R7, R8, R9, R10, R11, p and q are as defined in compound of formula (I). According to yet another embodiment, specifically provided are compounds of formula (I), in which ‘p’ is 1; R8is C1-8alkyl and ‘q’ is 0. According to yet another embodiment, specifically provided are compounds of formula (I), in which ‘p’ is 1; R8is methyl and ‘q’ is 0. According to yet another embodiment, specifically provided are compounds of formula (I), in which . According to yet another embodiment, specifically provided are compounds of formula (I), in which Q is

[0014]

[0015] According to another embodiment, specifically provided are compounds of formula (I), in which

[0016] R1is hydrogen or methyl; R2is -COOH, -C(O)2CH2CH3, -C(O)2CH(CH3)2, l,3,4-oxadiazol-2-yl or 5-methyl- l,3,4-oxadiazol-2-yl;

[0017] Rpis hydrogen

[0018] Rqis hydrogen; Rfis methyl;

[0019] ‘h’ is 0;

[0020] ‘m’ is 0;

[0021] ‘n’ is 0;

[0022] L1is

[0023]

[0024] According to another embodiment, specifically provided are compounds of formula (I), in which

[0025] R1is hydrogen or methyl; R2is -COOH, -C(O)2CH2CH3, -C(O)2CH(CH3)2, l,3,4-oxadiazol-2-yl or 5-methyl- l,3,4-oxadiazol-2-yl;

[0026] Rpis hydrogen

[0027] Rqis hydrogen;

[0028] Rfis methyl;

[0029] ‘h’ is 0;

[0030] ‘m’ is 0;

[0031] ‘n’ is 0;

[0032] wherein, ‘b’, ‘k’, Rz., Ry, X3, L2, ring U, R5, Rsare as defined in compound of formula (I). iii) VHL which is represented

[0033] R8, R9, R10, R11, p and q are as defined in compound of formula (I).

[0034] According to an embodiment, specifically provided are compounds of formula (I) with an DC50 value of less than 1000 nM, preferably less than 500 nM, more preferably less than 100 nM, with respect to IRAK-M degradation.

[0035] Further embodiments relating to groups R1, R2, R3, R4, Rp, Rq, Re, L1, Q, m, n and h (and groups defined therein) are described hereinafter in relation to the compounds of formula (II) or compounds of Formula (III). It is to be understood that these embodiments are not limited to use in conjunction with formula (II) or (III), but apply independently and individually to the compounds of formula (I). For example, in an embodiment described hereinafter, the invention specifically provides compounds of formula (II) or (III) in which Rpis hydrogen and consequently there is also provided a compound of formula (I) in which Rpis hydrogen.

[0036] The invention also provides a compound of formula (II), which is an embodiment of a compound of formula (I).

[0037] Accordingly the invention provides a compound of formula (II) or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein R1, R2, L1and Q are as defined in formula (I). According to one embodiment, specifically provided are compounds of formula (II), in which

[0038] R1is hydrogen or methyl;

[0039] R2is -COOH, -C(O)2CH2CH3, -C(O)2CH(CH3)2, l,3,4-oxadiazol-2-yl or 5-methyl- l,3,4-oxadiazol-2-yl;

[0040]

[0041]

[0042] 10

[0043]

[0044] According to an embodiment, specifically provided are compounds of formula (II) with an DC50 value of less than 1000 nM, preferably less than 500 nM, more preferably less than 100 nM, with respect to IRAK-M degradation.

[0045] The invention also provides a compound of formula (III), which is an embodiment of a compound of formula (I).

[0046] Accordingly the invention provides a compound of formula (III)

[0047] or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein R1, R2, ring P, ring D, ring E, W1, W2, W3and Q are as defined in formula (I).

[0048] According to one embodiment, specifically provided are compounds of formula (III), in which

[0049] R1is hydrogen or methyl;

[0050] R2is -COOH, -C(O)2CH2CH3, -C(O)2CH(CH3)2, l,3,4-oxadiazol-2-yl or 5-methyl- l,3,4-oxadiazol-2-yl;

[0051] W1is -C(O)- or -CH2-; ring P is C3-i2 cycloalkyl ring, Ce-uaryl or 3 to 15 membered heterocyclyl ring;

[0052] W2is -C(O)-, -CONH- or -Coring D is 3 to 15 membered heterocyclyl ring which is unsubstituted or substituted with one or more substituents selected from halogen or hydroxyl or 5-14 membered heteroaryl ring;

[0053] W3is absent or is selected from 3 to 15 membered heterocyclyl ring, -O-, -N-CH3-, - C(O)-, -(CRmRn)f-C(O)-, -(CRiRj)e-, -O-(CH2)I and -C=C-; ring E is 3 to 15 membered heterocyclyl ring which is unsubstituted or substituted with one or more substituents selected from halogen, hydroxyl, oxo or Ci-salkoxy;

[0054] R1and RJare hydrogen or halogen;

[0055] Rmand Rnare hydrogen;

[0056] ‘f is 1 or 2;

[0057] ‘e’ is 1, 2, 3 or 4;

[0058] 7’ is 2; Q is CLM which is selected from . According to one embodiment, specifically provided are compounds of formula (III), in which R1is hydrogen or methyl; R2is -COOH, -C(O)2CH2CH3, -C(O)2CH(CH3)2, 1,3,4-oxadiazol-2-yl or 5-methyl- 1,3,4-oxadiazol-2-yl; W1is –C(O)– or –CH2-; ring P is cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentyl, bicyclo[2.2.2]octyl, phenyl or piperidinyl; W2is –C(O)–, –CONH– or –CH2-; ring D is azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl or pyrazolyl which is unsubstituted or substituted with fluoro or hydroxyl; W3is absent or is selected from pyrrolidinyl, piperidinyl, –O–, –N-CH3–, –C(O)–, - (CH2)2-C(O)-, -CF2-C(O)-, -(CH2)e-, –O-(CH2)2– and –C≡C–; ring E is pyrrolidinyl, 2,3-dihydro-pyrrole, piperidinyl, piperazinyl, diazepanyl, 3,8- diazabicyclo[3.2.1]octan-8-yl or 2,5-diazabicyclo[2.2.1]heptan-2-yl which is unsubstituted or substituted with fluoro, hydroxyl, oxo or C1-8alkoxy or pyrazolyl, 2,6-diazaspiro[3.3]heptan- 2-yl, diazaspiro[3.5]nonan-2-yl, 2,7-diazaspiro[3.5]nonan-7-yl, 2,7-diazaspiro[4.4]nonan-2- yl; ‘f’ is 1 or 2; ‘e’ is 1, 2, 3 or 4; ‘l’ is 2; and W4is absent or –O–. Q is CLM which is selected from

[0059]

[0060] According to an embodiment, specifically provided are compounds of formula (III) with an DC50 value of less than 1000 nM, preferably less than 500 nM, more preferably less than 100 nM, with respect to IRAK-M degradation. Compounds of the present invention include the compounds in Examples 1-206. It should be understood that the formula (I), (II) and (III) structurally encompasses all geometrical isomers, stereoisomers, enantiomers and diastereomers, N-oxides, and pharmaceutically acceptable salts that may be contemplated from the chemical structure of the genera described herein. The present application also provides a pharmaceutical composition that includes at least one compound described herein and at least one pharmaceutically acceptable excipient (such as a pharmaceutically acceptable carrier or diluent). Preferably, the pharmaceutical composition comprises a therapeutically effective amount of at least one compound described herein. Pharmaceutical compositions comprising Compounds of the Invention may be prepared using conventional diluents or excipients and techniques known in the art. In one embodiment, the present invention relates to compound of formula (I’): or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein, X1is selected from N and CH; X2is selected from N and CH; R1is selected from hydrogen, halogen, hydroxyl, cyano, C1-8alkyl, C1-8alkoxy, C1-8alkoxyC1-8alkyl, hydroxylC1-8alkyl, haloC1-8alkyl, C(O)haloC1-8alkyl, C(O)C1-8alkyl, C3- 12cycloalkyl, and 3 to 15 membered heterocyclic ring; R2is selected from hydrogen, halogen, hydroxyl, C1-8alkyl, hydroxylC1-8alkyl, haloC1-8alkyl, C(O)C1-8alkyl, C(O)2Rxand C3-12cycloalkyl; each occurrence of R3’is selected from hydrogen, halogen, C1-8alkyl, hydroxyl, hydroxylC1-8alkyl, haloC1-8alkyl, C1-8alkoxy, C1-8alkoxyC1-8alkyl, C(O)C1-8alkyl, C3-12cycloalkyl or 3 to 15 membered heterocyclyl ring Rxis selected from hydrogen, halogen, hydroxyl, cyano, C1-8alkyl, C1-8alkoxy, C1-8alkoxyC1-8alkyl, hydroxylC1-8alkyl, haloC1-8alkyl, C(O)haloC1-8alkyl, C(O)C1-8alkyl, C3-12cycloalkyl, and 3 to 15 membered heterocyclic ring; R4’is selected from hydrogen, halogen, C1-8alkyl, C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; L1’is selected from –O-, -C(O)-, -NH- and –S-; ring A is selected from C6-14aryl, C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; ring B is selected from C6-14aryl, C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; ring C is selected from C6-14aryl, C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; each occurrence of R5’is independently selected from hydrogen, halogen, hydroxyl, cyano, oxo, C1-8alkyl, hydroxylC1-8alkyl, haloC1-8alkyl and C(O)C1-8alkyl; each occurrence of R6’is independently selected from hydrogen, halogen, hydroxyl, cyano, oxo, C1-8alkyl, hydroxylC1-8alkyl, haloC1-8alkyl and C(O)C1-8alkyl; L2’is selected from x and y independently represent the point of attachment; Z is absent or is selected from -O-, -C(O)-, -NH- and –S-; ring D is selected from, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; C6-14aryl, C3-12cycloalkyl ring E is selected from C6-14aryl, C3-12cycloalkyl, 5 to 12 membered spiroheterocyclyl ring, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; ring P is selected from C6-14aryl, C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; ring F is selected from C6-14aryl, C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; ring G is selected from C6-14aryl, C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; Y is absent or is selected from –O–, –C(O)–, –NH– and –S–; ring H is selected from C6-14aryl, C3-12cycloalkyl and 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; ring J is selected from C6-14aryl, C3-12cycloalkyl and 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; ring K is selected from C6-14aryl, C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; Rais independently selected from selected from hydrogen, halogen, hydroxyl, cyano, C1-8alkyl, C1-8alkoxy, C1-8alkoxyC1-8alkyl, hydroxylC1-8alkyl, haloC1-8alkyl, C(O)haloC1-8alkyl, C(O)C1-8alkyl, C3-12cycloalkyl, and 3 to 15 membered heterocyclic ring; Rbis independently selected from selected from hydrogen, halogen, hydroxyl, cyano, C1-8alkyl, C1-8alkoxy, C1-8alkoxyC1-8alkyl, hydroxylC1-8alkyl, haloC1-8alkyl, C(O)haloC1-8alkyl, C(O)C1-8alkyl, C3-12cycloalkyl, and 3 to 15 membered heterocyclic ring; Rcis independently selected from selected from hydrogen, halogen, hydroxyl, cyano, C1-8alkyl, C1-8alkoxy, C1-8alkoxyC1-8alkyl, hydroxylC1-8alkyl, haloC1-8alkyl, C(O)haloC1-8alkyl, C(O)C1-8alkyl, C3-12cycloalkyl, and 3 to 15 membered heterocyclic ring; Rdis independently selected from selected from hydrogen, halogen, hydroxyl, cyano, C1-8alkyl, C1-8alkoxy, C1-8alkoxyC1-8alkyl, hydroxylC1-8alkyl, haloC1-8alkyl, C(O)haloC1- 8alkyl, C(O)C1-8alkyl, C3-12cycloalkyl, and 3 to 15 membered heterocyclic ring; ‘m’’ is 0, 1 or 2; ‘n’’ is 0, 1 or 2; ‘h’’ is 0, 1 or 2; ‘t’ is 0, 1, 2, 3, 4 or 5; ‘r’ is 0, 1, 2, 3 or 4; ‘l’ is 0, 1, 2, 3 or 4; ‘g’ is 1, 2 or 3; and ‘s’ is 0, 1, 2, 3, 4, 5, 6, 7, 8 or 9; Q is the group is selected from E3 ubiquitin ligase binding moiety, selected from CLM (Cereblon E3 ubiquitin ligase) and VHL (Von Hippel-Lindau E3 ubiquitin ligase); MLM is an MDM2 E3 ubiquitin ligase; and IAP is a IAP E3 ubiquitin ligase; wherein CLM is selected from L3’is absent or is selected from -O-, -S- and –NH–; ring U is selected from C6-14aryl, C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; each occurrence of R7’is independently selected from halogen, hydroxyl, cyano, oxo, C1-8alkyl, haloC1-8alkyl, haloC1-8alkoxy, hydroxyC1-8alkyl, C(O)haloC1-8alkyl, C(O)C1-8alkyl, C6-14aryl, C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring ‘k’ is 0, 1, 2, 3, 4 or 5. In one embodiment, the present invention relates to compound of formula (II’) or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein, R1is selected from hydrogen, halogen, hydroxyl, cyano, C1-8alkyl, C1-8alkoxy, C1- 8alkoxyC1-8alkyl, hydroxylC1-8alkyl, haloC1-8alkyl, C(O)haloC1-8alkyl, C(O)C1-8alkyl, C3-12cycloalkyl, and 3 to 15 membered heterocyclic ring; R2is selected from halogen, hydroxyl, C1-8alkyl, hydroxylC1-8alkyl, haloC1-8alkyl, - C(O)C1-8alkyl, -C(O)2Rx, C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; wherein C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl are unsubstituted or substituted with one or more substituents selected from halogen, hydroxyl, cyano, oxo, C1-8alkyl, C1-8alkoxy, haloC1-8alkyl, haloC1-8alkoxy, hydroxyC1-8alkyl, -C(O) haloC1-8alkyl and -C(O)C1-8alkyl; Rxis selected from hydrogen, halogen, C1-8alkyl, hydroxylC1-8alkyl, haloC1-8alkyl; Rpis selected from hydrogen, halogen, hydroxyl, C1-8alkyl, hydroxylC1-8alkyl and haloC1-8alkyl; Rqis selected from hydrogen, halogen, hydroxyl, C1-8alkyl, hydroxylC1-8alkyl and haloC1-8alkyl; each occurrence of Reis independently selected from halogen, C1-8alkyl, hydroxylC1-8alkyl and haloC1-8alkyl; Rfis selected from hydrogen, halogen, hydroxyl, C1-8alkyl, hydroxylC1-8alkyl and haloC1-8alkyl; each occurrence of R3is independently selected from halogen, oxo, C1-8alkyl, hydroxyl, hydroxylC1-8alkyl, haloC1-8alkyl, C1-8alkoxy and C1-8alkoxyC1-8alkyl; each occurrence of R4is independently selected from halogen, hydroxyl, oxo, C1-8alkyl, hydroxylC1-8alkyl and haloC1-8alkyl; x and y independently represent the point of attachment; Z is absent or is selected from -O-, -C(O)-, -NH- and –S-; ring D is selected from 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; ring E is selected from 5 to 12 membered spiroheterocyclyl ring, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; ring P is selected from C6-14aryl, C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; W is absent or is selected from –O–, –C(O)–, –CONH, -(CH2)e-, –NH– and –S–; ring F is selected from C3-12cycloalkyl and 3 to 15 membered heterocyclyl ring; ring G is selected from C3-12cycloalkyl and 3 to 15 membered heterocyclyl ring; Y is absent or is selected from –O–, –C(O)–, –NH– and –S–; ring H is selected from C3-12cycloalkyl and 3 to 15 membered heterocyclyl ring; ring J is selected from C3-12cycloalkyl and 3 to 15 membered heterocyclyl ring; ring K is selected from 3 to 15 membered heterocyclyl ring and 5 to 12 membered spiroheterocyclyl ring; ring S is selected from C3-12cycloalkyl and 3 to 15 membered heterocyclyl ring; ring O is selected from C3-12cycloalkyl and 3 to 15 membered heterocyclyl ring; ring V is selected from C3-12cycloalkyl and 3 to 15 membered heterocyclyl ring; Ra, Rb, Rc, Rd, Ri, Rj, Rmand Rnare independently selected from selected from hydrogen, halogen, hydroxyl, C1-8alkyl, hydroxylC1-8alkyl and haloC1-8alkyl; Rcand Rd, together with the carbon atom to which they are attached to form C3-12 cycloalkyl ring; wherein C3-12 cycloalkyl ring is unsubstitued or substituted with one or more substituents selected from halogen, hydroxyl, oxo, C1-8alkyl, haloC1-8alkyl, hydroxyC1-8alkyl and haloC1-8alkyl; Rband Rc, together with the carbon atom to which they are attached to form C3-12 cycloalkyl ring; wherein C3-12cycloalkyl ring is unsubstitued or substituted with one or more substituents selected from halogen, hydroxyl, oxo, C1-8alkyl, haloC1-8alkyl, hydroxyC1-8alkyl and haloC1-8alkyl; ‘m’ is 0, 1 or 2; ‘n’ is 0, 1 or 2; ‘h’ is 0, 1 or 2; ‘t’ is 0, 1, 2, 3, 4 or 5; ‘r’ is 0, 1, 2, 3 or 4; ‘f’ is 1, 2 or 3; ‘e’ is 1, 2, 3, 4 or 5; ‘l’ is 0, 1, 2, 3 or 4; ‘j’ is 0, 1 or 2; ‘g’ is 1, 2 or 3; ‘s’ is 0, 1, 2, 3, 4, 5, 6, 7, 8 or 9; ‘i’ is 1, 2 or 3; and ‘d’ is 1, 2, 3, 4 or 5; Q is the group is selected from E3 ubiquitin ligase binding moiety, selected from CLM (Cereblon E3 ubiquitin ligase) and VHL (Von Hippel-Lindau E3 ubiquitin ligase); wherein CLM is selected from , X3is selected from CH, N or O; L2is absent or is selected from -O-, -C(O)-, -CONH-and –NH–; ring U is selected from C6-14aryl, C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; each occurrence of R5is independently selected from halogen, hydroxyl, cyano, oxo, C1-8alkyl, C1-8alkoxy, haloC1-8alkyl, haloC1-8alkoxy and hydroxyC1-8alkyl; R6is selected from hydrogen, halogen, hydroxyl, C1-8alkyl, C1-8alkoxy, haloC1-8alkyl, haloC1-8alkoxy, hydroxyC1-8alkyl and C(O)C1-8alkyl; each occurrence of R7is selected from halogen, hydroxyl, C1-8alkyl, hydroxyC1-8alkyl and haloC1-8alkyl; R8is selected from hydrogen, halogen, hydroxyl, C1-8alkyl, hydroxyC1-8alkyl and haloC1-8alkyl; each occurrence of R9is selected from halogen, hydroxyl, C1-8alkyl, C1-8alkoxy, haloC1-8alkyl, haloC1-8alkoxy and hydroxyC1-8alkyl; R10and R11is independently selected from hydrogen, C1-8alkyl, haloC1-8alkyl, hydroxyC1-8alkyl and C(O)C1-8alkyl; R10and R11, together with the nitrogen atom to which they are attached, form a 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; wherein 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring are each unsubstitued or substituted with one or more substituents selected from halogen, hydroxyl, oxo, C1-8alkyl, haloC1-8alkyl, hydroxyC1-8alkyl and haloC1-8alkyl; Ryis selected from halogen, hydroxyl, C1-8alkyl, haloC1-8alkyl and hydroxyC1-8alkyl; Rzis selected from hydrogen, C1-8alkyl, hydroxyC1-8alkyl and haloC1-8alkyl; ‘p’ is 0, 1, 2 or 3; ‘q’ is 0, 1, 2 or 3; ‘b’ is 0, 1 or 2 and ‘k’ is 0, 1, 2, 3, 4 or 5. Definitions The terms “halogen” or “halo” means fluorine (fluoro), chlorine (chloro), bromine (bromo), or iodine (iodo). The term “alkyl” refers to a hydrocarbon chain radical that includes solely carbon and hydrogen atoms in the backbone, containing no unsaturation, having from one to eight carbon atoms (i.e. C1-8alkyl), and which is attached to the rest of the molecule by a single bond. Examples of alkyl groups include, but not limited to, methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl, and 1,1-dimethylethyl (t-butyl). In some embodiments, the term “C1-6alkyl” refers to an alkyl chain having 1 to 6 carbon atoms, “C1-4alkyl” refers to an alkyl chain having 1 to 4 carbon atoms. Unless set forth or recited to the contrary, all alkyl groups described or claimed herein may be straight chain or branched. The term “haloalkyl” refers to at least one halo group (selected from F, Cl, Br or I), linked to an alkyl group having from one to eight carbon atoms as defined above (i.e. haloC1- 8alkyl). Examples of such haloalkyl moiety include, but are not limited to, trifluoromethyl, difluoromethyl and fluoromethyl groups. The term “haloC1-8alkyl” refers to at least one halo group linked an alkyl chain having 1 to 8 carbon atoms. Unless set forth or recited to the contrary, all haloalkyl groups described herein are straight chain or branched. The term “alkoxy” denotes an alkyl group, having from one to eight carbon atoms, attached via an oxygen linkage to the rest of the molecule (i.e. C1-8alkoxy). Representative examples of such groups are -OCH3 and -OC2H5. Unless set forth or recited to the contrary, all alkoxy groups described or claimed herein are straight chain or branched. The term “haloalkoxy” refers to an alkoxy group as described above which is substituted with one or more halogen atoms (i.e. haloC1-8alkoxy). Examples of “haloalkoxy” include but are not limited to fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2- trifluoroethoxy, pentafluoroethoxy, pentachloroethoxy, chloromethoxy, dichlorormethoxy, trichloromethoxy and 1-bromoethoxy. Unless set forth or recited to the contrary, all haloalkoxy groups described herein may be straight chain or branched. The term “alkoxyalkyl” or “alkyloxyalkyl” refers to an alkoxy or alkyloxy group as defined above directly bonded to an alkyl group as defined above (i.e. C1-8alkoxyC1-8alkyl or C1-8alkyloxyC1-8alkyl). Example of such alkoxyalkyl moiety includes, but are not limited to, - CH2OCH3 (methoxymethyl) and -CH2OC2H5 (ethoxymethyl). Unless set forth or recited to the contrary, all alkoxyalkyl groups described herein may be straight chain or branched. The term “hydroxyC1-8alkyl” refers to a C1-8alkyl group as defined above wherein one to three hydrogen atoms on different carbon atoms is / are replaced by hydroxyl groups (i.e. hydroxyC1-4alkyl). Examples of hydroxyC1-4alkyl moieties include, but are not limited to - CH2OH and -C2H4OH. The term “cycloalkyl” denotes a non-aromatic mono or polycyclic ring system of 3 to about 12 carbon atoms, (i.e.C3-12cycloalkyl). Examples of monocyclic cycloalkyl include but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. Examples of multicyclic cycloalkyl groups include, but are not limited to, perhydronapthyl, adamantyl and norbornyl groups, bridged cyclic groups or spirobicyclic groups, e.g. spiro(4,4)non-2-yl. The term “C3-6cycloalkyl” refers to the cyclic ring having 3 to 6 carbon atoms. Examples of “C3-6cycloalkyl” include but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. The term “aryl” refers to an aromatic radical having 6 to 14 carbon atoms (i.e. C6-14aryl), including monocyclic, bicyclic and tricyclic aromatic systems, such as phenyl, naphthyl etc. The term “heterocyclic ring” or “heterocyclyl” unless otherwise specified refers to substituted or unsubstituted non-aromatic 3 to 15 membered ring radical (i.e.3 to 15 membered heterocyclyl) which consists of carbon atoms and from one to five hetero atoms selected from nitrogen, phosphorus, oxygen and sulfur. The heterocyclic ring radical may be a mono-, bi- or tricyclic ring system, which may include fused, bridged or spiro ring systems, and the nitrogen, phosphorus, carbon, oxygen or sulfur atoms in the heterocyclic ring radical may be optionally oxidized to various oxidation states. In addition, the nitrogen atom may be optionally quaternized; also, unless otherwise constrained by the definition the heterocyclic ring or heterocyclyl may optionally contain one or more olefinic bond(s). Examples of such heterocyclic ring radicals include, but are not limited to azepinyl, azetidinyl, benzodioxolyl, benzodioxanyl, chromanyl, dioxolanyl, dioxaphospholanyl, decahydroisoquinolyl, indanyl, indolinyl, isoindolinyl, isochromanyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, oxazolinyl, oxazolidinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2- oxoazepinyl, octahydroindolyl, octahydroisoindolyl, perhydroazepinyl, piperazinyl, 4- piperidonyl, pyrrolidinyl, piperidinyl, phenothiazinyl, phenoxazinyl, quinuclidinyl, tetrahydroisquinolyl, tetrahydrofuryl or tetrahydrofuranyl, tetrahydropyranyl, thiazolinyl, thiazolidinyl, thiamorpholinyl, thiamorpholinyl sulfoxide and thiamorpholinyl sulfone. The heterocyclic ring radical may be attached to the main structure at any heteroatom or carbon atom that results in the creation of a stable structure. The terms “spiroheterocycloalkyl” or “spiroheterocyclyl”, as used herein, refers to a spirocycle wherein at least one of the rings is a heterocycle one or more of the carbon atoms can be substituted with a heteroatom (e.g., one or more of the carbon atoms can be substituted with a heteroatom in at least one of the rings). A spirocyclic heterocycle can contain between 5 and 12 atoms, at least one of which is a heteroatom selected from N, O, S and P. In some embodiments, a spirocyclic heterocycle can contain from 5 to 12 atoms, at least one of which is a heteroatom selected from N, O, S and P (i.e.5 to 12 membered spiroheterocyclyl). The term “heteroaryl” unless otherwise specified refers to 5 to 14 membered aromatic heterocyclic ring radical with one or more heteroatom(s) independently selected from N, O or S (i.e. 5 to 14 membered heteroaryl). The heteroaryl may be a mono-, bi- or tricyclic ring system. The heteroaryl ring radical may be attached to the main structure at any heteroatom or carbon atom that results in the creation of a stable structure. Examples of such heteroaryl ring radicals include, but are not limited to oxazolyl, isoxazolyl, imidazolyl, furyl, indolyl, isoindolyl, pyrrolyl, triazolyl, triazinyl, tetrazoyl, thienyl, oxadiazolyl, thiazolyl, isothiazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, benzofuranyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzopyranyl, carbazolyl, quinolinyl, isoquinolinyl, quinazolinyl, cinnolinyl, naphthyridinyl, pteridinyl, purinyl, quinoxalinyl, quinolyl, isoquinolyl, thiadiazolyl, indolizinyl, acridinyl, phenazinyl and phthalazinyl. The term “pharmaceutically acceptable salt” includes salts prepared from pharmaceutically acceptable bases or acids including inorganic or organic bases and inorganic or organic acids. Examples of such salts include, but are not limited to, acetate, benzenesulfonate, benzoate, bicarbonate, bisulfate, bitartrate, borate, bromide, camsylate, carbonate, chloride, clavulanate, citrate, dihydrochloride, edetate, edisylate, estolate, esylate, fumarate, gluceptate, gluconate, glutamate, glycollylarsanilate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isothionate, lactate, lactobionate, laurate, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methylsulfate, mucate, napsylate, nitrate, N-methylglucamine ammonium salt, oleate, oxalate, pamoate (embonate), palmitate, pantothenate, phosphate, diphosphate, polygalacturonate, salicylate, stearate, sulfate, subacetate, succinate, tannate, tartrate, teoclate, tosylate, triethiodide and valerate. Examples of salts derived from inorganic bases include, but are not limited to, aluminum, ammonium, calcium, copper, ferric, ferrous, lithium, magnesium, manganic, manganous, potassium, sodium, and zinc. The term “treating” or “treatment” of a state, disorder or condition includes: (a) preventing or delaying the appearance of clinical symptoms of the state, disorder or condition developing in a subject that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition; (b) inhibiting the state, disorder or condition, i.e., arresting or reducing the development of the disease or at least one clinical or subclinical symptom thereof; or (c) relieving the disease, i.e., causing regression of the state, disorder or condition or at least one of its clinical or subclinical The term “subject” includes mammals (especially humans) and other animals, such as domestic animals (e.g., household pets including cats and dogs) and non-domestic animals (such as wildlife). A “therapeutically effective amount” means the amount of a compound that, when administered to a subject for treating a state, disorder or condition, is sufficient to effect such treatment. The “therapeutically effective amount” will vary depending on the compound, the disease and its severity and the age, weight, physical condition and responsiveness of the subject to be treated. The compounds of formula (I), (II) or (III) may contain asymmetric or chiral centers, and, therefore, exist in different stereoisomeric forms. It is intended that all stereoisomeric forms of the compounds of formula (I) as well as mixtures thereof, including racemic mixtures, form part of the present invention. In addition, the present invention embraces all geometric and positional isomers. Diastereomeric mixtures can be separated into their individual diastereomers on the basis of their physical chemical differences by methods well known to those skilled in the art, such as, for example, by chromatography and / or fractional crystallization. Enantiomers can be separated by converting the enantiomeric mixture into a diastereomeric mixture by reaction with an appropriate optically active compound (e.g., chiral auxiliary such as a chiral alcohol or Mosher's acid chloride), separating the diastereomers and converting (e.g., hydrolysing) the individual diastereomers to the corresponding pure enantiomers. Enantiomers can also be separated by use of chiral HPLC column. The chiral centres of the present invention can have the S or R configuration as defined by the IUPAC 1974. The terms "salt" or "solvate", and the like, is intended to equally apply to the salt, solvate and prodrug of enantiomers, stereoisomers, tautomers or racemates of the compounds of the present invention. PHARMACEUTICAL COMPOSITIONS The compounds of the invention are typically administered in the form of a pharmaceutical composition. Such compositions can be prepared using procedures well known in the pharmaceutical art and comprise at least one compound of the invention. The pharmaceutical compositions described herein comprise one or more compounds described herein and one or more pharmaceutically acceptable excipients. METHODS OF TREATMENT The compounds of the present patent application are IRAK-M degraders and can be useful in the treatment of diseases or disorder mediated by IRAK-M. Accordingly, the compounds and the pharmaceutical compositions of this invention are useful in the treatment of diseases or disorder mediated by IRAK-M. Compounds of the present patent application may be useful in the treatment of cancer. Any of the methods of treatment described herein comprise administering an effective amount of a compound according to Formula (I) or a pharmaceutically acceptable salt thereof, to a subject (particularly a human) in need thereof. The present inventions further relates to the use of the compounds described herein in the preparation of a medicament for the treatment of diseases mediated by IRAK-M. GENERAL METHODS OF PREPARATION The compounds, described herein, including those of general formula (I), (II) or (III) or intermediates and specific examples are prepared through the synthetic methods as depicted in synthetic schemes 1 to 3. Furthermore, in the following schemes, where specific acids, bases, reagents, coupling reagents, solvents, etc. are mentioned, it is understood that other suitable acids, bases, reagents, coupling reagents, solvents etc. may be used and are included within the scope of the present invention. The modifications to reaction conditions, for example, temperature, duration of the reaction or combinations thereof, are envisioned as part of the present invention. The compounds obtained using the general reaction sequences may be of insufficient purity. These compounds can be purified using any of the methods for purification of organic compounds known to persons skilled in the art, for example, crystallization or silica gel or alumina column chromatography using different solvents in suitable ratios. All possible geometrical isomers and stereoisomers are envisioned within the scope of this invention. General schemes A general approach for the preparation of compound of the formula (IA and IB) [wherein R1, Rx, R5, t, r and k are as defined in the general description] is depicted in synthetic scheme 1. Synthetic Scheme-1:

[0061] The reaction of compound of formula (1) with the compound of formula (2) in the presence of suitable base and suitable solvent gives the compound of formula (3). The suitable base used in the reaction may be trimethylamine or potassium carbonate. The suitable solvent may be selected from DMF, diethyl ether, THF or combination thereof. The compound of formula (3) on intramolecular cyclisation in the presence of suitable base gives the compound of formula (4), which on reaction with suitable halogenating reagent such as phosphorus oxychloride or thionyl chloride in the presence of suitable base gives the compound of formula (5) (where X is halogen). The suitable base used in the reaction may be trimethylamine or diethyl aniline. The halo displacement reaction of the compound of formula (5) with tert-butyl 4-((1s,4s)-4-aminocyclohexyl)piperazine-1-carboxylate (Cis amine) gives the compound of formula (6). The suitable base used in the reaction may be trimethylamine or potassium carbonate. The suitable solvent may be selected from acetonitrile, DMF, diethyl ether, THF or combination thereof. The reaction of compound of formula (6) with the compound of formula (7) in the presence of suitable base and solvent gives the compound of formula (8). The suitable base used in the reaction may be trimethylamine or potassium carbonate. The suitable solvent may be selected from acetonitrile, ethanol, DMF, diethyl ether or combination thereof. The deprotection of compound of formula (8) in the acidic condition gives the compound of formula (9). The suitable acid used in the reaction may be selected from saturate hydrochloride acid in dry ethyl acetate or 1,4-dioxane or Trifluoroacetic acid. The reaction of compound of formula (9) with the compound of formula (10) in the presence of suitable solvent and base gives compound of formula (11). The suitable base used in the reaction may be selected from trimethylamine, N,N-diisopropylethylamine, pyridine or 4-Dimethylaminopyridine. The suitable solvent may be selected from dry THF, dry-dichloromethane, dry 1,2-dichloroethane or a mixture thereof. The coupling reaction of the compound of formula (11) with suitable amine Intermediate of the compound of formula (12A) (wherein X4and X5are CH or N) in the presence of suitable reagent and suitable solvent gives the compound of formula (IA). The coupling reaction of (11) with amine Intermediate of the compound of formula (12B) (wherein X4and X5are CH or N) in the presence of suitable reagent and suitable solvent gives the compound of formula (IB). The suitable reagent used in the reaction may be HATU. The suitable solvent used in the reaction may be selected from DMF, THF, DCM or a combination thereof. A general approach for the preparation of compound of the formula (IIB) [wherein R1, Rx, Re, Rf, L2, R5, Rz, l and k are as defined in the general description] is depicted in synthetic scheme 2. Synthetic Scheme-2:

[0062] The coupling reaction of compound of formula (9) with (1s,4s)-4- (methoxycarbonyl)cyclohexane-1-carboxylic acid (13) in the presence of suitable coupling reagents and suitable base gives the compound of formula (14). The suitable coupling reagents used in the reaction may be HATU, TBTU or EDCI.HCl. The suitable base used in the reaction may be trimethylamine, pyridine or DIEPA. The reaction may be carried out in a suitable solvent may be selected from DMF, diethyl ether, THF or combination thereof. The aqueous hydrolysis of the compound of formula (14) using suitable base gives the compound of the formula (15). The suitable base used in the reaction may be sodium hydroxide or potassium hydroxide. The coupling reaction of the compound of formula (15) with suitable amine Intermediate of the compound of formula (16A) (wherein X4and X5are CH or N) in the presence of suitable reagent and suitable solvent gives the compound of formula (IIA). The coupling reaction of (15) with amine Intermediate of the compound of formula (16B) (wherein X4and X5are CH or N) in the presence of suitable reagent and suitable solvent gives the compound of formula (IIB). The suitable reagent used in the reaction may be HATU. The suitable solvent used in the reaction may be selected from DMF, THF, DCM or a combination thereof. A general approach for the preparation of compound of the formula (IIIB) [wherein R1, Rx, Rf, Re, R5, l and k are as defined in the general description] is depicted in synthetic scheme 3. Synthetic Scheme-3:

[0063] The reaction of compound of formula (8) with hydrazine derivative of the formula (17) in the presence of suitable solvent gives the compound of formula (18). The cyclization of the compound of formula (18) using suitable reagent in presence of suitable solvent gives the compound of the formula (19). The suitable reagent used in the reaction may be alkyl orthoformate. The suitable solvent used in the reaction may be selected from ethanol, isopropanol or mixtures thereof. The deprotection of the compound of formula (19) in the acidic condition gives the the compound of formula (20). The suitable acid used in the reaction may be selected from saturate hydrochloride acid in dry ethyl acetate or 1,4-dioxane or Trifluoroacetic acid. The coupling reaction of the compound of formula (20) with suitable amine Intermediate of the compound of formula (21A) (wherein X4and X5are CH or N) in the presence of suitable reagent and suitable solvent gives the compound of formula (IIIA). The coupling reaction of (20) with amine Intermediate of the compound of formula (21B) (wherein X4and X5are CH or N) in the presence of suitable reagent and suitable solvent gives the compound of formula (IIIB). The suitable reagent used in the reaction may be HATU. The suitable solvent used in the reaction may be selected from DMF, THF, DCM or a combination thereof. INTERMEDIATES Intermediate 1 4-(4-((1s,4s)-4-((5-(Ethoxycarbonyl)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl) amino)pyrimidin-4-yl)amino)cyclohexyl)piperazin-1-yl)-4-oxobutanoic acid Step 1: Ethyl (E)-3-amino-2-((ethoxycarbonyl)carbamoyl)but-2-enoate To a suspension of ethyl 3-aminocrotonate (28 g, 217 mmol) in diethyl ether (120 mL) was added a solution of ethoxycarbonylisocyanate (26 g, 217 mmol) in diethyl ether (60 mL) dropwise under ice-cooling, and the mixture was stirred at the same temperature for 5 h. The reaction mixture was concentrated under reduced pressure to obtain 38 g of the title compound used as such for next step. Step 2: Ethyl 2,4-dihydroxy-6-methylpyrimidine-5-carboxylate To a stirred solution of step 1 Intermediate (38 g, 155.73 mmol) in water (200 mL), was added 25% aqueous triethylamine solution (70 mL). The reaction mixture was stirred at 70 °C for overnight. The reaction mixture was concentrated under reduced pressure and cooled to 0 °C, acidified with acetic acid. The precipitated obtained was collected by filtration and dried to obtain 12 g of the desired product.1H NMR (400 MHz, DMSO-d6): ^ 1.23 (t, J = 6.8 Hz, 3H), 2.16 (s, 3H), 4.18 (q, J = 7.2 Hz, 2H), 11.25 (br s, 2H). Step 3: Ethyl 2,4-dichloro-6-methylpyrimidine-5-carboxylate To a stirred solution of step 2 Intermediate (5.0 g, 27.17 mmol) in phosphorus oxychloride (50 mL) was added N, N-diethyl aniline (10 drops) at 0 ºC. The reaction mixture was heated at 90 ºC for 5 h. The excess of phosphorus oxychloride was removed under reduced pressure. The reaction mixture poured into ice water and extracted with ethyl acetate (100 mL x 3). The combined organic layers were washed with saturated solution of sodium bicarbonate and water followed by brine. The solution was dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain desired product.1H NMR (400 MHz, DMSO-d6): ^ 1.44 (t, J = 7.2 Hz, 3H), 2.59 (s, 3H), 4.49 (q, J = 7.2 Hz, 2H). Step 4: Ethyl 4-(((1s,4s)-4-(4-(tert-butoxycarbonyl)piperazin-1-yl)cyclohexyl)amino)-2- chloro-6-methylpyrimidine-5-carboxylate To a stirred solution of ethyl 2,4-dichloro-6-methylpyrimidine-5-carboxylate (4.4 g, 18.7 mmol) in acetonitrile (45 mL) was added tert-butyl 4-((1s,4s)-4-aminocyclohexyl)piperazine- 1-carboxylate (5.3 g, 18.7 mmol) and triethylamine (10.5 mL, 74.8 mmol) in sealed tube. The resulting reaction mixture was heated to 100 ºC for 1 h. The solvent was concentrated under reduced pressure. The residue obtained was purified by flash silica chromatography with the elution gradient being 30:70 of acetone in pet ether to obtain 7.1 g of the desired product.1H NMR (400 MHz, DMSO-d6): ^ 1.33 (t, J = 7.2 Hz, 3H), 1.47 (s, 9H), 1.50-1.78 (m, 8H), 2.23- 2.42 (m, 5H), 3.27-3.34 (m, 4H), 4,10-4.15 (m, 1H), 4.34 (q, J = 6.8 Hz, 2H), 8.32 (s, 1H), 8.51 (d, J = 8.0 Hz, 1H). Step 5: Ethyl 4-(((1s,4s)-4-(4-(tert-butoxycarbonyl)piperazin-1-yl)cyclohexyl)amino)-6- methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate To a stirred solution of step 4 Intermediate (7.1 g, 14.76 mmol) in dry ethanol (90 mL) was added 1-Methyl-1H-pyrazol-4-amine hydrochloride (2.16 g, 16.2 mmol) and resulting mixture was heated in sealed tube at 90 ºC for 1 h and cooled to RT. The crude product was purified by silica gel chromatography with the elution gradient 0 to 6% methanol in DCM to obtain 8.4 g of the desired product.1H NMR (400 MHz, DMSO-d6): ^ 1.32 (t, J = 7.2 Hz, 3H), 1.41 (s, 9H), 1.55-2.01 (m, 12H), 2.47-2.55 (m, 4H), 3.79 (s, 3H), 4.26 (q, J = 6.8 Hz, 2H), 7.51 (s, 1H), 7.74 (s, 1H), 8.85 (d, J = 6.4 Hz, 1H), 9.65 (s, 1H). Step 6: Ethyl 4-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)-6-(((1s,4s)-4-(piperazin-1- yl)cyclohexyl)amino)pyrimidine-5-carboxylate hydrochloride To a solution of step 5 Intermediate (5.4 g, 9.96 mmol) in dry DCM (40 mL) was added hydrochloric acid (4 M in dioxane, 30 mL) at RT and mixture was stirred for 2 h. The solvent was concentrated under reduced pressure. The residue obtained was treated with diethyl ether to obtain 5.3 g the desired product.1H NMR (400 MHz, DMSO-d6): ^ 1.45 (t, J = 7.2 Hz, 6H), 1.81-1.93 (m, 4H), 2.23-2.28 (m, 4H), 2.75 (s, 3H), 3.55-3.77 (m, 7H), 3.94 (s, 1H), 3.98 (s, 3H), 4.42-4.51 (m, 2H), 7.60 (s, 1H), 7.83 (s, 1H), 7.90 (s, 1H), 8.00 (s, 1H). Step 7: 4-(4-((1s,4s)-4-((5-(ethoxycarbonyl)-6-methyl-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidin-4-yl)amino)cyclohexyl)piperazin-1-yl)-4-oxobutanoic acid To a solution of step 6 Intermediate (2.5 g, 4.87 mmol) in DIPEA (2.6 mL, 14.62 mmol) was added dihydrofuran-2,5-dione (487 mg, 4.87 mmol) in DCM (80 mL) and heated at 50 °C for 1 h. The reaction mixture was cooled to RT and the solvent was removed under reduced pressure. The residue obtained was treated with diethyl ether followed by n-pentane to obtain desired product which was used directly for the next step. The structure and chemical name of the intermediates prepared by following the procedure described above are given in below Table 1. Table 1: Structure and chemical name of Intermediates 2-27.

[0064] Intermediate 20 6-methyl-N2-(1-methyl-1H-pyrazol-4-yl)-5-(1,3,4-oxadiazol-2-yl)-N4-((1s,4s)-4-(piperazin- 1-yl)cyclohexyl)pyrimidine-2,4-diamine 2,2,2-trifluoroacetate salt Step 1: tert-Butyl 4-((1s,4s)-4-((5-(hydrazinecarbonyl)-6-methyl-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidin-4-yl)amino)cyclohexyl)piperazine-1-carboxylate To a stirred solution of ethyl 4-(((1s,4s)-4-(4-(tert-butoxycarbonyl)piperazin-1- yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate (step 5 of Intermediate 1) (3 g, 5.53 mmol) in dry ethanol (30 mL) was added hydrazine hydrate (25 mL) and resulting mixture was refluxed for overnight. The solvent was removed under reduced pressure and the crude residue obtained was triturated with diethyl ether to obtain 2.5 g of the titled compound. ESI-MS (m / z): 529.1 (M+H)+. Step 2: tert-butyl 4-((1s,4s)-4-((6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)-5-(1,3,4- oxadiazol-2-yl)pyrimidin-4-yl)amino)cyclohexyl)piperazine-1-carboxylate A mixture of step 1 Intermediate (2.5 g, 4.73 mmol) and triethyl orthoformate (35 mL) was heated to 100 ºC for 1 h. The excess of triethyl orthofomate was evaportaed under reduced pressure and the crude residue obtained was purified to yield 1.5 g of the titled comopund.1H NMR (400 MHz, DMSO-d6): ^ 1.39 (s, 9H), 1.60-1.90 (m, 8H), 2.28-2.60 (m, 8H), 3.26-3.38 (m, 4H), 3.79 (s, 3H), 4.30-4.34 (m, 1H), 7.52 (s, 1H), 7.78 (s, 1H), 8.94 (d, J = 6.8 Hz, 1H), 9.29 (d, J = 5.2 Hz, 1H), 9.65 (s, 1H).; ESI-MS (m / z): 539.0 (M+H)+. Step 3: N2-(1-methyl-1H-pyrazol-4-yl)-5-(1,3,4-oxadiazol-2-yl)-N4-((1s,4s)-4-(piperazin-1- yl)cyclohexyl)pyrimidine-2,4-diamine 2,2,2-trifluoroacetate salt To a stirred solution of step 2 Intermediate (250 mg, 0.36 mmol) in dichloromethane (4 mL) was added trifluro acetic acid (2mL) at 0 ºC to RT and the resulting mixture was stirred for 1 h. The solvent concentrated under reduced pressure and crude residue obtained was uesd for next step. ESI-MS (m / z): 439.0 (M+H)+. The structure and chemical name of the intermediates prepared by following the procedure described above are given in below Table 2. Table 2: Structure and chemical name of Intermediates 21 to 22.

[0065] Intermediate 28 2-((1-Methyl-1H-pyrazol-4-yl)amino)-4-(((1s,4s)-4-(piperazin-1- yl)cyclohexyl)amino)pyrimidine-5-carboxylic acid hydrochloride To a stirred solution of ethyl 4-(((1s,4s)-4-(4-(tert-butoxycarbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate (analogous step 5 of Intermediate 4) (300mg, 0.53 mmol) in methanol (5 mL) and water ( 3 ml) was added sodium hydroxide (63 mg, 1.59 mmol)) The resulting mixture was refluxed for 6 h. The solvent was removed under reduced pressure and the residue obtained was taken in water cooled to 0 ºC and acidified with 6N hydrochloric acid and stirred overnight to obtain 175 mg of the titled compound. ESI-MS (m / z): 400.1 (M+H)+. The structure and chemical name of the intermediates prepared by following the procedure described above are given in below Table 3. Table 3: Structure and chemical name of Intermediate 29.

[0066] EXAMPLES Example 1 Ethyl 4-(((1s,4s)-4-(4-(4-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)piperazin-1-yl)ethyl)piperidin-1-yl)-4-oxobutanoyl)piperazin-1-yl)cyclohexyl)amino)-6- methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate The title compound was prepared by coupling reaction of Intermediate 1 (2.64 g, 4.86 mmol) with 2-(2,6-dioxopiperidin-3-yl)-5-(4-(2-(piperidin-4-yl)ethyl) piperazin-1- yl)isoindoline-1,3-dione hydrochloride (2.56 g, 4.86 mmol) in dry DMF (50 mL) were added DIPEA (2.5 mL, 14.58 mmol) and HATU (1.7 g, 4.66 mmol). The resulting mixture was stirred at RT for overnight. The reaction mixture was diluted with water and filtered. The solid obtained was dried and purified by SFC to obtain 1.3 g of the product.1H NMR (400 MHz, DMSO-d6) ^ 1.06-2.09 (m, 11H), 1.31 (t, J = 6.8 Hz, 3H), 2.20-2.62 (m, 11H), 2.84-3.00 (m, 2H), 3.40-3.45 (m, 6H), 3.79 (s, 3H), 3.87 (d, J = 12.2 Hz, 1H), 4.20-3.35 (m, 4H), 5.04-5.11 (m, 1H), 7.25 (d, J = 8.4Hz, 1H), 7.34 (s, 1H), 7.50 (s, 1H), 7.68 (d, J = 8.4Hz, 1H), 7.75 (s, 1H), 7.82 (d, J = 6.0 Hz, 1H), 9.61 (s, 1H), 11.09 (s, 1H). ESI-MS (m / z): 978.6 (M+H). The details of synthesis and analytical data of the examples prepared from the above mentioned methods are given below in Table 4. Table 4: Structure, Chemical name, Intermediate used and analytical data of Examples 2−43, 45, 47, 49-52, 54-63, 65, 66, 68, 69, 71-73, 75, 77-85, 87-89, 91, 93-98, 100-132, 135-141, 144-190, 193-206. Example 44 Ethyl 4-(((1s,4s)-4-(4-(2-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin- 4-yl)ethyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate The title compound was prepared was by reaction of ethyl 2-((1-methyl-1H-pyrazol-4- yl)amino)-4-(((1s,4s)-4-(4-(2-(piperidin-4-yl)ethyl)piperazin-1- yl)cyclohexyl)amino)pyrimidine-5-carboxylate hydrochloride (180 mg, 0.29 mmol) with 2- (2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione (81.6 mg, 0.29 mmol) using triethyl amine (0.16 mL, 1.18 mmol) in dry DMSO (45 mL) to obtain 41 mg of the product. ESI-MS (m / z): 796.5 (M+H)+. Example 46 Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)piperidin-4-yl)-1H-pyrazol-4-yl)carbamoyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate The title compound was prepared by the reaction of ethyl 2-((1-methyl-1H-pyrazol-4- yl)amino)-4-(((1S,4s)-4-(4-((1r,4R)-4-((1-(piperidin-4-yl)-1H-pyrazol-4-yl) carbamoyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino) pyrimidine-5- carboxylate hydrochlride (300 mg, 0.391 mmol) with 2-(2,6-dioxopiperidin-3-yl)-5- fluoroisoindoline-1,3-dione (108 mg, 0.391 mmol) using DIPEA (0.335 mL, 1.95 mmol) in DMSO (5 mL) at 100 ºC for 1 h. After work up and purification to obtain 41 mg of the product. ESI-MS (m / z): 987.5 (M+H)+. Example 48 Ethyl 4-(((1s,4s)-4-(4-(3-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin- 4-yl)propyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine- 5-carboxylate The title compound was prepared by the reaction of ethyl 2-((1-methyl-1H-pyrazol-4- yl)amino)-4-(((1s,4s)-4-(4-(3-(piperidin-4-yl)propyl)piperazin-1-yl)cyclohexyl) amino)pyrimidine-5-carboxylate hydrochloride (200 mg, 0.31 mmol) with 2-(2,6- dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione (88 mg, 0.31 mmol) using triethyl amine (0.17 mL, 1.27 mmol) in dry THF (5 mL) to obtain 45 mg of the product. ESI-MS (m / z): 810.5 (M+H)+. Example 53 Ethyl 4-(((1s,4s)-4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)pyrrolidin-3- yl)methyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate The title compound was prepared by the reaction of ethyl 2-((1-methyl-1H-pyrazol-4- yl)amino)-4-(((1s,4s)-4-(4-(pyrrolidin-3-ylmethyl)piperazin-1-yl)cyclohexyl) amino) pyrimidine-5-carboxylate hydrochloride (200 mg, 0.39 mmol) with 2-(2,6-dioxopiperidin-3- yl)-5-fluoroisoindoline-1,3-dione (108 mg, 0.39 mmol) using triethyl amine (0.22 mL) in dry DMSO (5 mL) to obtain 48 mg of the product. ESI-MS (m / z): 768.5 (M+H)+. Example 64 Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-((1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)piperidin-4-yl)methyl)-1H-pyrazol-4-yl)carbamoyl) cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate The title compound was prepared by reaction of ethyl 2-((1-methyl-1H-pyrazol-4-yl)amino)- 4-(((1S,4s)-4-(4-((1r,4R)-4-((1-(piperidin-4-ylmethyl)-1H-pyrazol-4- yl)carbamoyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino) pyrimidine-5- carboxylate hydrochloride (240 mg, 0.293 mmol) with 2-(2,6-dioxopiperidin-3-yl)-5- fluoroisoindoline-1,3-dione (81 mg, 0.293 mmol) using DIPEA (0.251 mL, 1.46 mmol) in DNSO (5 mL) to obtain 34 mg of the product. ESI-MS (m / z): 1000.1 (M+H)+. Example 67 Ethyl 4-(((1s,4s)-4-(4-((1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)piperazin-1-yl)cyclohexyl)amino)-2-((1- methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate The title compound was prepared was prepared by reaction of ethyl 2-((1-methyl-1H-pyrazol- 4-yl)amino)-4-(((1s,4s)-4-(4-((1-(piperidin-4-ylmethyl)piperidin-4-yl) methyl)piperazin-1- yl)cyclohexyl)amino)pyrimidine-5-carboxylate hydrochloride (123 mg, 0.197 mmol) with 2- (2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione (54 mg, 0.197 mmol) using triethyl amine (0.11 mL, 0.78 mmol) in dry DMSO (3 mL) by heating at 120 ºC for 1 h. After work up and SFC purification to yield 15 mg of the product. ESI-MS (m / z): 877.6 (M+H)+. Example 70 Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin- 5-yl)pyrrolidin-3-yl)ethyl)piperazine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate The title compound was prepared by the reaction of ethyl 2-((1-methyl-1H-pyrazol-4- yl)amino)-4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(pyrrolidin-3-yl)ethyl)piperazine-1- carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)pyrimidine-5- carboxylate hydrochloride (264 mg, 0.35 mmol) with 2-(2,6-dioxopiperidin-3-yl)-5- fluoroisoindoline-1,3-dione (97 mg, 0.35 mmol) using triethyl amine (0.19 mL, 1.41 mmol) in DMSO (5 mL) to obtain 45 mg of the product. ESI-MS (m / z): 1004.2 (M+H)+. Example 74 Ethyl 4-(((1S,4s)-4-(4-((1R,4R)-4-(4-(((3R)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)pyrrolidin-3-yl)methyl)piperazine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate The title compound was prepared by the reaction of ethyl 2-((1-methyl-1H-pyrazol-4- yl)amino)-4-(((1S,4s)-4-(4-((1S,4R)-4-(4-(((S)-pyrrolidin-3-yl)methyl) piperazine-1- carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl) amino)pyrimidine-5- carboxylate hydrochloride (205 mg, 0.279 mmol) with 2-(2,6-dioxopiperidin-3-yl)-5- fluoroisoindoline-1,3-dione (77 mg, 0.279 mmol) using triethyl amine (0.15 mL, 1.11 mmol) in dry DMSO (7 mL) to obtain 51 mg of the product. ESI-MS (m / z): 990.6 (M+H)+. Example 76 Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)piperidin-4-yl)methyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate The title compound was prepared by the reaction of ethyl 2-((1-methyl-1H-pyrazol-4- yl)amino)-4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(piperidin-4-ylmethyl)piperidine-1- carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)pyrimidine-5- carboxylate hydrochloride (160 mg, 0.187 mmol) with 2-(2,6-dioxopiperidin-3-yl)-5- fluoroisoindoline-1,3-dione (51 mg, 0.1871 mmol) using triethyl amine (0.1 mL, 0.748 mmol) in DMSO (3 mL) to obtain 5 mg of the product. ESI-MS (m / z): 1004.0 (M+H)+. Example 86 Ethyl 4-((4-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1- yl)ethyl)piperidin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine- 5-carboxylate The title compound was prepared was prepared by the reaction of ethyl 2-chloro-4-((4-(4-(2- (4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)ethyl)piperidin-1- yl)cyclohexyl)amino)pyrimidine-5-carboxylate (510 mg, 0.693 mmol) with 1-methyl-1H- pyrazol-4-amine hydrochloride (138 mg, 1.04 mmol) in dry ethanol at reflux for 1 h. Evaporation and purification of crude to yield 30 mg of the product. ESI-MS (m / z): 796.3 (M+H)+. Example 90 Ethyl 4-(((1S,4s)-4-(4-((1R,4R)-4-(4-(2-((3R)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)pyrrolidin-3-yl)ethyl)piperazine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate The title compound was prepared by the reaction of ethyl 2-((1-methyl-1H-pyrazol-4- yl)amino)-4-(((1S,4s)-4-(4-((1S,4R)-4-(4-(2-((S)-pyrrolidin-3-yl)ethyl)piperazine-1- carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)pyrimidine-5- carboxylate hydrochloride (201 mg, 0.268 mmol) with 2-(2,6-dioxopiperidin-3-yl)-5- fluoroisoindoline-1,3-dione (111 mg, 0.403 mmol) using triethyl amine (0.15 mL, 1.074 mmol) in dry DMSO (5 mL) to obtain 77 mg of the product. ESI-MS (m / z): 1004.8 (M+H)+. Example 92 Ethyl 4-(((1S,4s)-4-(4-((1S,4R)-4-(4-(((3S)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)pyrrolidin-3-yl)methyl)piperazine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate The title compound was prepared by the reaction of ethyl 2-((1-methyl-1H-pyrazol-4- yl)amino)-4-(((1S,4s)-4-(4-((1R,4R)-4-(4-(((R)-pyrrolidin-3-yl)methyl)piperazine-1- carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)pyrimidine-5- carboxylate (200 mg, 0.237 mmol) with 2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3- dione (98 mg, 0.356 mmol) using triethyl amine (0.2 mL, 0.529 mmol) in DMSO (2 mL) to obtain 55 mg of the product. ESI-MS (m / z): 990.2 (M+H)+. E l 99 Ethyl 4-(((1S,4s)-4-(4-((1S,4R)-4-(4-(2-((3S)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)pyrrolidin-3-yl)ethyl)piperazine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate The title compound was prepared by the reaction of ethyl 2-((1-methyl-1H-pyrazol-4- yl)amino)-4-(((1S,4s)-4-(4-((1R,4R)-4-(4-(2-((R)-pyrrolidin-3-yl)ethyl)piperazine-1- carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)pyrimidine-5- carboxylate hydrochloride (360 mg, 0.481 mmol) with 2-(2,6-dioxopiperidin-3-yl)-5- fluoroisoindoline-1,3-dione (199 mg, 0.721 mmol) using triethyl amine (0.27 mL, 0.97 mmol) in DMSO (8 mL) to obtain 54 mg of the product. ESI-MS (m / z): 1004.6 (M+H)+. Example 133 Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(4-(4-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)piperazin- 1-yl)butyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)- 6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate The title compound was separated from example 23 by SFC chiral purification method to obtain 35 mg of the desired product. ESI-MS (m / z): 992.0 (M+H)+. Example 134 Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(4-(4-(4-((R)-2,6-dioxopiperidin-3-yl)phenyl)piperazin- 1-yl)butyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)- 6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate The title compound was separated from example 23 by SFC chiral purification using method to obtain 35 mg of the product. ESI-MS (m / z): 991.5 (M+H)+. Example 142 Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-(((R)-2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate The title compound was separated from example 97 by SFC chiral purification method to obtain 34 mg of the product. ESI-MS (m / z): 968.3 (M+H)+. Example 143 Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-(((S)-2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylatexylate The title compound was separated from example 97 by SFC chiral purification method to obtain 34 mg of the product. ESI-MS (m / z): 968.5 (M+H)+. Example 191 Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(1-(4-(((S)-2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)-4-hydroxypiperidin-4-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate The title compound was separated from example 97 by SFC chiral purification using Methanol:DCM (1:1) to obtain 55 mg of the product. ESI-MS (m / z): 998.2 (M+H)+. Example 192 Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(1-(4-(((R)-2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)-4-hydroxypiperidin-4-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate The title compound was separated from example 97 by SFC chiral purification method using Methanol:DCM (1:1) to obtain 50 mg of the product. ESI-MS (m / z): 998.2 (M+H)+. PHARMACOLOGICAL ACTIVITY Degradation of cellular IRAKM in U937 cells: U937 cells (ATCC# CRL-1593.2TM) were seeded in a 96 well plate and incubated for an hour. Compounds of the present invention were added to these cells, followed by incubation for 24 h at 37 °C with 5% CO2. After incubation, cells were lysed after treatment with 1x HTRF lysis buffer mixed with blocking buffer (Cisbio# Total-IRAK-M Detection Kit). Levels of IRAK-M were estimated in lysed cells by HTRF assay (Cisbio# Total-IRAK-M Detection Kit). Herein, total IRAK-M was detected in a sandwich assay format using two separate specific antibodies, one labelled with Eu3+-Cryptate (donor) and the other with d2 (acceptor), which were added and incubated for 24 h. When the dyes are in close proximity, a light source (laser or flash lamp) excites the donor, causing a fluorescence resonance energy transfer (FRET) towards the acceptor, which fluoresces at a certain wavelength (665 nm) and read on SPARK according to the kit instructions. The percentage of degradation of IRAK-M by the test compound of the present invention was calculated based on the FRET ratio of 665 nm / 620 nm. DC50 values were calculated from the dose response curve by nonlinear regression analysis using GraphPad Prism software. The compounds prepared were tested using the above assay procedure and the results obtained are given in Table 5. Percentage degradation at concentrations of 1.0 µM is given in the Table-5 along with DC50 (nM) details for the compounds of the present invention. The DC50(nM) values are set forth in Table 5 wherein “A” refers to an DC50value of less than or equal to 50 nM, “B” refers to DC50 value in range of 50.01 to 100.0 nM, “C” refers to DC50 value in range of 100.01 to 500 nM and “D” refers to DC50 values more than or equal to 500 nM. Table 5:

[0067] Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as described above. All publications and patent applications cited in this application are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated herein by reference.

Claims

WHAT IS CLAIMED IS:

1. A compound of formula (I)or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein, X1is selected from N and CH; X2is selected from N and CH; R1is selected from hydrogen, C1-8alkyl, hydroxylC1-8alkyl and haloC1-8alkyl; R2is selected from -C(O)2Rxand 5-14 membered heteroaryl ring; wherein 5-14 membered heteroaryl is unsubsituted or substituted with one or more substituents selected from C1-8alkyl, haloC1-8alkyl and hydroxyC1-8alkyl; Rxis selected from hydrogen and C1-8alkyl; Rpis selected from hydrogen and C1-8alkyl; Rqis selected from hydrogen and C1-8alkyl; each occurrence of Reis independently selected from halogen, C1-8alkyl, hydroxylC1- 8alkyl and haloC1-8alkyl; each occurrence of R3is independently selected from halogen, C1-8alkyl, hydroxyl, hydroxylC1-8alkyl and haloC1-8alkyl; each occurrence of R4is independently selected from halogen, C1-8alkyl, hydroxylC1-8alkyl and haloC1-8alkyl;x and y independently represent the point of attachment; Z is absent or is selected from –O–, –C(O) –, –NH– and –S–; ring D is selected from 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; wherein 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl are each unsubstituted or substituted with one or more substituents selected from halogen, hydroxyl or oxo; ring E is selected from 5 to 12 membered spiroheterocyclyl ring, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; wherein 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl are each unsubstituted or substituted with one or more substituents selected from halogen, hydroxyl, oxo or C1-8alkoxy; ring P is selected from C6-14aryl, C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; wherein C6-14aryl, C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl are each unsubstituted or substituted with one or more substituents selected from halogen, hydroxyl or oxo; W1is absent or is selected from –C(O)–, –CONH– and –CH2-; W2is absent or is selected from –C(O)–, –CONH– and –CH2-; W3is absent or is selected from 3 to 15 membered heterocyclyl ring, –O–, –N-CH3–, – C(O)–, –CONH–, – (CRmRn)f-C(O) –, – (CRiRj)e–, –O-(CH2)l– and –C≡C–; W4is absent or –O–; ring F is 3 to 15 membered heterocyclyl ring; ring G is 3 to 15 membered heterocyclyl ring; Y is absent or is selected from –O–, –C(O)–, –NH– and –S–;ring H is selected from C3-12cycloalkyl and 3 to 15 membered heterocyclyl ring; T1is absent or is selected from –C(O)–, –CONH– and–CH2–; T2is absent or is selected from –C(O)–, –CONH– and –(CH2)i–;. ring J is selected from C3-12cycloalkyl and 3 to 15 membered heterocyclyl ring; ring K is selected from 3 to 15 membered heterocyclyl ring and 5 to 12 membered spiroheterocyclyl ring; ring S is selected from C3-12cycloalkyl and 3 to 15 membered heterocyclyl ring; ring O is selected from C3-12cycloalkyl and 3 to 15 membered heterocyclyl ring; Ra, Rb, Rc, Rd, Ri, Rj, Rmand Rnare independently selected from selected from hydrogen, halogen, hydroxyl, C1-8alkyl, hydroxylC1-8alkyl and haloC1-8alkyl; Rcand Rd, together with the carbon atom to which they are attached to form C3-12 cycloalkyl ring; wherein C3-12cycloalkyl ring is unsubstitued or substituted with one or more substituents selected from halogen, hydroxyl, oxo, C1-8alkyl, haloC1-8alkyl, hydroxyC1-8alkyl and haloC1-8alkyl; Rband Rc, together with the carbon atom to which they are attached to form C3-12 cycloalkyl ring; wherein C3-12cycloalkyl ring is unsubstitued or substituted with one or more substituents selected from halogen, hydroxyl, oxo, C1-8alkyl, haloC1-8alkyl, hydroxyC1-8alkyl and haloC1-8alkyl; ‘m’ is 0, 1 or 2; ‘n’ is 0, 1 or 2; ‘h’ is 0, 1 or 2; ‘t’ is 0, 1, 2, 3, 4 or 5; ‘r’ is 0, 1, 2, 3 or 4; ‘f’ is 1, 2 or 3; ‘e’ is 1, 2, 3, 4 or 5; ‘l’ is 0, 1, 2, 3 or 4; ‘j’ is 0, 1 or 2; ‘g’ is 1, 2 or 3; ‘s’ is 0, 1, 2, 3, 4, 5, 6, 7, 8 or 9; ‘i’ is 1, 2 or 3;‘d’ is 1, 2, 3, 4 or 5; ‘a’ is 1, 2, 3, 4 or 5; Q is the group is selected fromE3 ubiquitin ligase binding moiety, selected from CLM (Cereblon E3 ubiquitin ligase) and VHL (Von Hippel-Lindau E3 ubiquitin ligase); wherein the CLM is selected fromthe VHL is selected from ,X3is selected from CH, N and O; L2is absent or is selected from –O–, –C(O) –, –CONH– and –NRs; ring U is selected from C6-14aryl, C3-12cycloalkyl, 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; each occurrence of R5is independently selected from halogen, hydroxyl, oxo, C1-8alkyl, haloC1-8alkyl and hydroxyC1-8alkyl; R6is selected from hydrogen, halogen, hydroxyl, C1-8alkyl, C1-8alkoxy, haloC1-8alkyl, haloC1-8alkoxy, hydroxyC1-8alkyl and C(O)C1-8alkyl; each occurrence of R7is selected from halogen, hydroxyl, C1-8alkyl, hydroxyC1-8alkyl and haloC1-8alkyl;R8is selected from hydrogen, halogen, hydroxyl, C1-8alkyl, hydroxyC1-8alkyl and haloC1-8alkyl; each occurrence of R9is selected from halogen, hydroxyl, C1-8alkyl, C1-8alkoxy, haloC1- 8alkyl, haloC1-8alkoxy and hydroxyC1-8alkyl; R10and R11is independently selected from hydrogen, C1-8alkyl, haloC1-8alkyl and hydroxyC1-8alkyl; R10and R11, together with the nitrogen atom to which they are attached, form a 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring; wherein 3 to 15 membered heterocyclyl ring and 5-14 membered heteroaryl ring are each unsubstitued or substituted with one or more substituents selected from halogen, hydroxyl, oxo, C1-8alkyl, haloC1-8alkyl, hydroxyC1-8alkyl and haloC1-8alkyl; Rsis selected from hydrogen and C1-8alkyl; Ryis selected from halogen, hydroxyl, C1-8alkyl, haloC1-8alkyl and hydroxyC1-8alkyl; Rzis selected from hydrogen, C1-8alkyl, hydroxyC1-8alkyl and haloC1-8alkyl; ‘p’ is 0, 1, 2 or 3; ‘q’ is 0, 1, 2 or 3; ‘b’ is 0, 1 or 2; and ‘k’ is 0, 1, 2, 3, 4 or 5.

2. The compound of claim 1, wherein R1is hydrogen or methyl.

3. The compound of claim 1, wherein R2is -COOH, -C(O)2CH2CH3, -C(O)2CH(CH3)2, 1,3,4-oxadiazol-2-yl or 5-methyl-1,3,4-oxadiazol-2-yl.

4. The compound of claim 1, wherein L1is,.

5. The compound of any one of claims 1 to 4, wherein L1is.

6. The compound of claim 5, wherein W1is –C(O)– or –CH2–; ring P is C3-12cycloalkyl ring, C6-14aryl or 3 to 15 membered heterocyclyl ring;W2is –C(O)–, –CONH– or –CH2–; ring D is 3 to 15 membered heterocyclyl ring which is unsubstituted or substituted with one or more substituents selected from halogen or hydroxyl or 5-14 membered heteroaryl ring; W3is absent or is selected from 3 to 15 membered heterocyclyl ring, –O–, –N-CH3–, – C(O)–, –(CRmRn)f-C(O)–, –(CRiRj)e–, –O-(CH2)l– and –C≡C–; ring E is 3 to 15 membered heterocyclyl ring which is unsubstituted or substituted with one or more substituents selected from halogen, hydroxyl, oxo or C1-8alkoxy; Riand Rjare hydrogen or halogen; Rmand Rnare hydrogen; ‘f’ is 1 or 2; ‘e’ is 1, 2, 3 or 4; ‘l’ is 2; and W4is absent or –O–.

7. The compound of claim 5, wherein W1is –C(O)–or –CH2-; ring P is cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentyl, bicyclo[2.2.2]octyl, phenyl or piperidinyl; W2is –C(O)–, –CONH– or –CH2-; ring D is azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl or pyrazolyl which is unsubstituted or substituted with fluoro or hydroxyl; W3is absent or is selected from pyrrolidinyl, piperidinyl, –O–, –N-CH3–, –C(O)–, – (CH2)2-C(O) –, –CF2-C(O)–, –(CH2)e–, –O-(CH2)2– and –C≡C–; ring E is pyrrolidinyl, 2,3-dihydro-pyrrole, piperidinyl, piperazinyl, diazepanyl, 3,8- diazabicyclo[3.2.1]octan-8-yl or 2,5-diazabicyclo[2.2.1]heptan-2-yl which is unsubstituted or substituted with fluoro, hydroxyl, oxo or C1-8alkoxy or pyrazolyl, 2,6-diazaspiro[3.3]heptan- 2-yl, diazaspiro[3.5]nonan-2-yl, 2,7-diazaspiro[3.5]nonan-7-yl, 2,7-diazaspiro[4.4]nonan-2- yl; ‘f’ is 1 or 2; ‘e’ is 1, 2, 3 or 4; ‘l’ is 2; and W4is absent or –O–.

8. The compound of any one of claims 4 to 7, wherein L1is selected from:

10. The compound of claim 9, wherein T1is -C(O)- or –CH2–; ring J is C3-12 cycloalkyl ring or 3 to 15 membered heterocyclyl ring; T2is -C(O)- or –(CH2)i–; ring K is 3 to 15 membered heterocyclyl ring or 5 to 12 membered spiroheterocyclyl ring; ‘i’ is 1 or 3; and T3is absent or is selected from.

11. The compound of claim 9, wherein T1is –C(O)– or –CH2–; ring J is cyclohexyl or piperidinyl; T2is –C(O)– or –(CH2)i–; ring K is piperazinyl, piperidinyl, 3,9-diazaspiro[5.5]undecanyl, 2,7- diazaspiro[3.5]nonan-2-yl, 2,9-diazaspiro[5.5]undecan-9-yl, 2,6-diazaspiro[3.3]heptan-2-yl or 2,7-diazaspiro[3.5]nonan-7-yl; ‘i’ is 1 or 3; and.

12. The compound of any one of claims 9 to 11, wherein L1is selected from:.

13. The compound of claim 1, wherein L1is.

14. The compound of claim 13, wherein Z is absent or -C(O)-; ring D is 3 to 15 membered heterocyclyl ring; ring E is 3 to 15 membered heterocyclyl ring; ‘t’ is 2, 3 or 4 and ‘r’ is 1, 2 or 3.

15. The compound of claim 13, wherein Z is absent or -C(O)-; ring D is piperidinyl; ring E is piperazinyl; ‘t’ is 2, 3 or 4 and ‘r’ is 1, 2, or 3.

16. The compound of any one of claims 13 to 15, wherein L1is18. The compound of claim 17, wherein Raand Rbare independently selected from hydrogen or methyl; Rcand Rdare independently selected from hydrogen or methyl; or Rcand Rdare joined together with the carbon atom attached to form cyclopentyl ring; or Rband Rcand are join together with the carbon atom attached to form cyclopropyl, cyclobutyl or cyclohexyl ring; ring F is piperidinyl; ring G is piperazinyl; ‘j’ is 0 or 1; and ‘g’ is 2.

19. The compound any one of claims 17 to 18, wherein L1is ,22. The compound of any one claims 1 to 21, wherein Q is represented byiii) VHL which is represented by24. The compound of claim 22, wherein25. The compound of any one claims 22 to 24, wherein Q is6. The compound of any one of claims 1 to 25, whereinR1is hydrogen or methyl;R2is -COOH, -C(O)2CH2CH3, -C(O)2CH(CH3)2, l,3,4-oxadiazol-2-yl or 5-methyl- l,3,4-oxadiazol-2-yl;Rpis hydrogenRqis hydrogen;Reis methyl;‘h’ is 0;‘m’ is 0;‘n’ is 0;or a stereoisomer or a pharmaceutically acceptable salt thereof.

28. The compound of claim 27, wherein R1is hydrogen or methyl; R2is -COOH, -C(O)2CH2CH3, -C(O)2CH(CH3)2, 1,3,4-oxadiazol-2-yl or 5-methyl- 1,3,4-oxadiazol-2-yl; W1is –C(O)– or –CH2–; ring P is C3-12 cycloalkyl ring, C6-14aryl or 3 to 15 membered heterocyclyl ring; W2is –C(O)–, –CONH– or –CH2–; ring D is 3 to 15 membered heterocyclyl ring which is unsubstituted or substituted with one or more substituents selected from halogen or hydroxyl or 5-14 membered heteroaryl ring; W3is absent or is selected from 3 to 15 membered heterocyclyl ring, –O–, –N-CH3–, – C(O)–, –(CRmRn)f-C(O)–, –(CRiRj)e–, -O-(CH2)land –C≡C–; ring E is 3 to 15 membered heterocyclyl ring which is unsubstituted or substituted with one or more substituents selected from halogen, hydroxyl, oxo or C1-8alkoxy; Riand Rjare hydrogen or halogen; Rmand Rnare hydrogen; ‘f’ is 1 or 2; ‘e’ is 1, 2, 3 or 4; ‘l’ is 2; Q is CLM which is selected.

29. The compound of any one of claims 27 to 28, whereinR1is hydrogen or methyl; R2is COOH, C(O)2CH2CH3, C(O)2CH(CH3)2, 1,3,4-oxadiazol-2-yl or 5-methyl-1,3,4- oxadiazol-2-yl; W1is –C(O)– or –CH2-; ring P is cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentyl, bicyclo[2.2.2]octyl, phenyl or piperidinyl; W2is –C(O)–, –CONH– or –CH2-; ring D is azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl or pyrazolyl which is unsubstituted or substituted with fluoro or hydroxyl; W3is absent or is selected from pyrrolidinyl, piperidinyl, –O–, –N-CH3–, –C(O)–, - (CH2)2-C(O)-, -CF2-C(O)-, -(CH2)e-, –O-(CH2)2– and –C≡C–; ring E is pyrrolidinyl, 2,3-dihydro-pyrrole, piperidinyl, piperazinyl, diazepanyl, 3,8- diazabicyclo[3.2.1]octan-8-yl or 2,5-diazabicyclo[2.2.1]heptan-2-yl which is unsubstituted or substituted with fluoro, hydroxyl, oxo or C1-8alkoxy or pyrazolyl, 2,6-diazaspiro[3.3]heptan- 2-yl, diazaspiro[3.5]nonan-2-yl, 2,7-diazaspiro[3.5]nonan-7-yl, 2,7-diazaspiro[4.4]nonan-2- yl; ‘f’ is 1 or 2; ‘e’ is 1, 2, 3 or 4; ‘l’ is 2; and W4is absent or –O–. Q is CLM which is selected from ,, , , ,30. A compound selected from Ethyl 4-(((1s,4s)-4-(4-(4-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)piperazin-1-yl)ethyl)piperidin-1-yl)-4-oxobutanoyl)piperazin-1-yl)cyclohexyl)amino)-6- methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)piperazin-1-yl)methyl)piperidin-1-yl)-4-oxobutanoyl)piperazin-1-yl)cyclohexyl)amino)-6- methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(3-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)piperazin-1-yl)ethyl)piperidin-1-yl)propanoyl)piperazin-1-yl)cyclohexyl)amino)-6- methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(4-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-1- yl)ethyl)piperidin-1-yl)-4-oxobutanoyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1- methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(10-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)piperazin-1-yl)decanoyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H- pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl) phenyl) piperazin-1-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate; Ethyl 4-(((1s,4s)-4-(4-(5-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-1- yl)ethyl)piperidin-1-yl)-5-oxopentanoyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1- methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(4-(4-((4-(4-(2,6-dioxopiperidin-3-yl)phenyl) piperazin-1- yl)methyl)piperidin-1-yl)-4-oxobutanoyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1- methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(4-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)piperazin-1-yl)ethyl)piperidin-1-yl)-4-oxobutanoyl) piperazin-1-yl)cyclohexyl)amino)-2- ((1-methyl-1H-pyrazol-4-yl)amino) pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)piperazin-1-yl)methyl)piperidin-1-yl)-4-oxobutanoyl)piperazin-1-yl)cyclohexyl)amino)-2- ((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-(2,6-dioxopiperidin-3-yl) phenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl) piperazin-1-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(4-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)piperazin-1-yl)ethyl)piperidin-1-yl)-2,2-dimethyl-4-oxobutanoyl)piperazin-1- yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate; Ethyl 4-(((1s,4s)-4-(4-(4-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)piperazin-1-yl)ethyl)piperidin-1-yl)-3,3-dimethyl-4-oxobutanoyl)piperazin-1- yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(4-(4-(4-(2,6-dioxopiperidin-3-yl) phenyl)piperazin-1-yl)butyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino) pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(3-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl) piperazin-1- yl)ethyl)piperidine-1-carbonyl)bicyclo[1.1.1]pentane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(4-(4-(3-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl) piperazin-1- yl)propyl)piperidin-1-yl)-4-oxobutanoyl)piperazin-1-yl)cyclohexyl) amino)-6-methyl-2-((1- methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(2-(1-(2-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin- 1-yl)ethyl)piperidin-1-yl)-2-oxoethyl)cyclopentyl)acetyl) piperazin-1-yl)cyclohexyl)amino)- 6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxy; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl) piperazine-1- carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H- pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(4-(4-((4-(4-(2,6-dioxopiperidin-3-yl)-3-fluorophenyl) piperazin-1-yl)methyl)piperidin-1-yl)-4-oxobutanoyl)piperazin-1-yl)cyclohexyl)amino)-6- methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(4-(4-(4-(2,6-dioxopiperidin-3- yl)phenyl)piperazin-1-yl)butyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin- 1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate; Ethyl 4-(((1R,4s)-4-(4-((1S,2R)-2-(4-(2-(4-(4-(2,6-dioxopiperidin-3- yl)phenyl)piperazin-1-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate; Ethyl 4-(((1s,4s)-4-(4-(4-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-1- yl)ethyl)piperidin-1-yl)-4-oxobutanoyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H- pyrazol-4-yl)amino)pyrimidine-5-carboxylate;Ethyl 4-(((1S,4s)-4-(4-((1R,2R)-2-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl) phenyl)piperazin-1-yl)ethyl)piperidine-1-carbonyl)cyclopropane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate; Ethyl 4-(((1s,4s)-4-(4-(4-(4-((4-(4-(2,6-dioxopiperidin-3-yl)phenyl) piperazin-1- yl)methyl)piperidin-1-yl)-4-oxobutanoyl)piperazin-1- yl)cyclohexyl) amino)-2-((1-methyl- 1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1R,4s)-4-(4-((1S,4R)-4-(((S)-1-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4- methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2- yl)carbamoyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1- methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1s,4S)-4-(4-(2-(4-(4-(2,6-dioxopiperidin-3- yl)phenyl)piperazin-1-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperazin-1-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperazin-1-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)-6-(((1S,4s)-4-(4-((1r,4R)-4-(4- (2-(4-(4-(1-methyl-2,6-dioxopiperidin-3-yl)phenyl)piperazin-1-yl)ethyl)piperidine-1- carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)pyrimidine-5- carboxylate; Ethyl 4-(((1s,4s)-4-(4-(3-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl) piperazin-1- yl)ethyl)piperidine-1-carbonyl)bicyclo[1.1.1]pentane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate;Ethyl 4-(((1s,4s)-4-(4-(4-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-1- yl)ethyl)piperidine-1-carbonyl)benzoyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1- methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1R,4s)-4-(4-((1S,2S)-2-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl) phenyl)piperazin-1-yl)ethyl)piperidine-1-carbonyl)cyclobutane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate; Ethyl 4-(((1s,4s)-4-(4-(4-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl) piperazin-1- yl)ethyl)piperidine-1-carbonyl)bicyclo[2.2.2]octane-1-carbonyl) piperazin-1- yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino) pyrimidine-5- carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1s,4S)-4-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperazin-1-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(9-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin- 5-yl)-3,9-diazaspiro[5.5]undecane-3-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)-1H-pyrazol-1-yl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((9-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)-3,9-diazaspiro[5.5]undecan-3-yl)methyl)piperidine-1- carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H- pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(6-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-1- yl)ethyl)piperidin-1-yl)-6-oxohexanoyl)piperazin-1-yl)cyclohexyl) amino)-6-methyl-2-((1- methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(3-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-1- yl)ethyl)piperidine-1-carbonyl)cyclopentane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-6- methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate;Ethyl 4-(((1s,4s)-4-(4-(2-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)piperidin-4-yl)ethyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(7-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin- 5-yl)-2,7-diazaspiro[3.5]nonane-2-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperidin-4-yl)-1H-pyrazol-4-yl)carbamoyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperazin-1-yl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(3-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)piperidin-4-yl)propyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-4-yl)piperazin-1-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(3-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl) piperazin-1- yl)ethyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-6- methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((7-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)-2,7-diazaspiro[3.5]nonan-2-yl)methyl)piperidine-1- carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H- pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)pyrrolidin-3-yl)methyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(3-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperazin-1-yl)methyl)pyrrolidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1S,4R)-4-((3S)-3-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1S,4R)-4-((3R)-3-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; 2-(2,6-Dioxopiperidin-3-yl)-5-(4-(2-(1-((1R,4r)-4-(4-((1s,4S)-4-((2-((1-methyl-1H- pyrazol-4-yl)amino)-5-(1,3,4-oxadiazol-2-yl)pyrimidin-4-yl)amino) cyclohexyl)piperazine-1- carbonyl)cyclohexane-1-carbonyl)piperidin-4-yl)ethyl)piperazin-1-yl)isoindoline-1,3-dione; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin- 5-yl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1- methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(2-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin- 5-yl)-2,9-diazaspiro[5.5]undecane-9-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(6-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin- 5-yl)-2,6-diazaspiro[3.3]heptane-2-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(3-(4-(4-(2,6-dioxopiperidin-3- yl)phenyl)piperazin-1-yl)propyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-(((1r,4R)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidine-1- carbonyl)cyclohexyl)methyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate;Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-((1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperidin-4-yl)methyl)-1H-pyrazol-4-yl)carbamoyl) cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(2-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin- 5-yl)-2,7-diazaspiro[3.5]nonane-7-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-((1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)piperazin-1-yl)cyclohexyl)amino)-2-((1- methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(4-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperazin-1-yl)butyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 2-((1-methyl-1H-pyrazol-4-yl)amino)-4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(4-(4-(4- (1-methyl-2,6-dioxopiperidin-3-yl)phenyl)piperazin-1-yl)butyl)piperidine-1- carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)pyrimidine-5- carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)pyrrolidin-3-yl)ethyl)piperazine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(4-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperazin-1-yl)butyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((2-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)-2,7-diazaspiro[3.5]nonan-7-yl)methyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H- pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-((4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)methyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1R,4R)-4-(4-(((3R)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)pyrrolidin-3-yl)methyl)piperazine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)-6-(((1S,4s)-4-(4-((1r,4R)-4-(4- (4-(4-(4-(1-methyl-2,6-dioxopiperidin-3-yl)phenyl)piperazin-1-yl) butyl)piperidine-1- carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl) cyclohexyl)amino)pyrimidine-5- carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; 2-(2,6-Dioxopiperidin-3-yl)-5-(4-((1-((1R,4r)-4-(4-((1s,4S)-4-((2-((1-methyl-1H- pyrazol-4-yl)amino)-5-(1,3,4-oxadiazol-2-yl)pyrimidin-4-yl)amino)cyclohexyl)piperazine-1- carbonyl)cyclohexane-1-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)isoindoline-1,3- dione; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(3-(4-(4-(2,6-dioxopiperidin-3- yl)phenyl)piperazin-1-yl)propyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperazin-1-yl)propyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(3-(4-(2,6-dioxopiperidin-3-yl) piperazin-1- yl)propyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)- 2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate;Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((7-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)-2,7-diazaspiro[4.4]nonan-2-yl)methyl)piperidine-1- carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H- pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)-1,4-diazepan-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(4-(2,6-dioxopiperidin-3-yl) piperazin-1- yl)ethyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2- ((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperidin-1-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-((4-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin- 1-yl)ethyl)piperidin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)piperidin-1-yl)methyl)piperidine-1-carbonyl)benzoyl)piperazin-1-yl)cyclohexyl)amino)-2- ((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(3-(4-(4-(2,6-dioxopiperidin-3- yl)phenyl)piperidin-1-yl)propyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl) piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; 2-(2,6-Dioxopiperidin-3-yl)-5-(4-((1-((1R,4r)-4-(4-((1s,4S)-4-((6-methyl-2-((1- methyl-1H-pyrazol-4-yl)amino)-5-(1,3,4-oxadiazol-2-yl)pyrimidin-4- yl)amino)cyclohexyl)piperazine-1-carbonyl)cyclohexane-1-carbonyl)piperidin-4- yl)methyl)piperazin-1-yl)isoindoline-1,3-dione;Ethyl 4-(((1S,4s)-4-(4-((1R,4R)-4-(4-(2-((3R)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)pyrrolidin-3-yl)ethyl)piperazine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1S,4R)-4-(4-(((3S)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)pyrrolidin-3-yl)methyl)piperazine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-((4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidin-1-yl)methyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; 2-(2,6-Dioxopiperidin-3-yl)-5-(4-(2-(1-((1R,4r)-4-(4-((1s,4S)-4-((6-methyl-2-((1- methyl-1H-pyrazol-4-yl)amino)-5-(1,3,4-oxadiazol-2-yl)pyrimidin-4- yl)amino)cyclohexyl)piperazine-1-carbonyl)cyclohexane-1-carbonyl)piperidin-4- yl)ethyl)piperazin-1-yl)isoindoline-1,3-dione; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(4-(4-(4-(2,6-dioxopiperidin-3-yl) phenyl)piperidin-1-yl)butyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl) piperazin-1- yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)piperazin-1-yl)propyl)piperidine-1-carbonyl) cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl) amino)-2- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl) amino)pyrimidine-5-carboxylate;3-(4-(4-(3-(1-((1R,4r)-4-(4-((1s,4S)-4-((2-((1-Methyl-1H-pyrazol-4-yl)amino)-5- (1,3,4-oxadiazol-2-yl)pyrimidin-4-yl)amino)cyclohexyl)piperazine-1-carbonyl)cyclohexane- 1-carbonyl)piperidin-4-yl)propyl)piperazin-1-yl)phenyl)piperidine-2,6-dione; Ethyl 4-(((1S,4s)-4-(4-((1S,4R)-4-(4-(2-((3S)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)pyrrolidin-3-yl)ethyl)piperazine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)pyrrolidin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin- 5-yl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-1- oxoisoindolin-5-yl)piperazin-1-yl)propyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1- oxoisoindolin-5-yl)piperazin-1-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(3-(3-(4-(2,6-dioxopiperidin-3-yl)phenyl)-3,8- diazabicyclo[3.2.1]octan-8-yl)propyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; 2-(2,6-Dioxopiperidin-3-yl)-5-(1-(2-(1-((1R,4r)-4-(4-((1s,4S)-4-((6-methyl-2-((1- methyl-1H-pyrazol-4-yl)amino)-5-(1,3,4-oxadiazol-2-yl)pyrimidin-4- yl)amino)cyclohexyl)piperazine-1-carbonyl)cyclohexane-1-carbonyl)piperidin-4- yl)ethyl)piperidin-4-yl)isoindoline-1,3-dione; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin- 5-yl)piperidin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate;Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(3-(4-(4-(2,6-dioxopiperidin-3- yl)phenyl)piperidin-1-yl)propyl)piperazine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(7-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)hept- 6-ynoyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(3-(4-(4-(2,6-dioxopiperidin-3- yl)phenyl)piperidin-1-yl)propyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate; 2-(2,6-Dioxopiperidin-3-yl)-5-(4-(2-(1-((1R,4r)-4-(4-((1s,4S)-4-((6-methyl-5-(5- methyl-1,3,4-oxadiazol-2-yl)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4- yl)amino)cyclohexyl)piperazine-1-carbonyl)cyclohexane-1-carbonyl)piperidin-4- yl)ethyl)piperazin-1-yl)isoindoline-1,3-dione; Ethyl 4-(((1s,4s)-4-(4-(6-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)hex-5- ynoyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((2-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)-2,7-diazaspiro[3.5]nonan-7-yl)methyl)piperidine-1- carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1-methyl- 1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-5-yl)-2,3-dihydro-1H-pyrrol-1-yl)ethyl)piperidine-1-carbonyl)cyclohexane- 1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-((4-(4-((1r,4r)-4-(4-((2-(4-(2,6-dioxopiperidin-3-yl)phenyl)-2,7- diazaspiro[3.5]nonan-7-yl)methyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin- 1-yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate;Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin- 1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(3-(4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)propyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(4-(4-(3-(2,6-dioxopiperidin-3- yl)phenyl)piperazin-1-yl)butyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(3-(3-(4-(4-(2,6-dioxopiperidin-3- yl)phenyl)piperazin-1-yl)propyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(3-(4-(4-(2,6-dioxopiperidin-3- yl)phenyl)piperazin-1-yl)-3-oxopropyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(3-(4-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3- fluorophenyl)piperazin-1-yl)propyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(3-(4-(4-(2,6-dioxopiperidin-3-yl)-2- fluorophenyl)piperazin-1-yl)propyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(3-(4-(4-(2,6-dioxopiperidin-3- yl)phenyl)piperazin-1-yl)propyl)piperazine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate;Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(4-(4-(2,6-dioxopiperidin-3- yl)phenyl)piperazin-1-yl)ethoxy)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(3-(4-(4-(2,6-dioxopiperidin-3- yl)phenyl)piperazin-1-yl)pyrrolidin-1-yl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-3- oxoisoindolin-5-yl)piperazin-1-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(4-(4-(2-(2,6-dioxopiperidin-3- yl)phenyl)piperazin-1-yl)butyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(3-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin- 1-yl)-[1,4'-bipiperidine]-1'-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(3-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)-N- methylacetamido)propyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(3-(4-(4-(2,6-dioxopiperidin-3-yl)-3- fluorophenyl)piperazin-1-yl)propyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; 3-((3-Fluoro-4-(4-((1-((1R,4r)-4-(4-((1s,4S)-4-((2-((1-methyl-1H-pyrazol-4- yl)amino)-5-(1,3,4-oxadiazol-2-yl)pyrimidin-4-yl)amino)cyclohexyl)piperazine-1- carbonyl)cyclohexane-1-carbonyl)piperidin-4-yl)methyl)piperazin-1- yl)phenyl)amino)piperidine-2,6-dione; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(4-(4-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)piperazin-1-yl)butyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate;Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(4-(4-(4-((R)-2,6-dioxopiperidin-3- yl)phenyl)piperazin-1-yl)butyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(3-(2-(4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)ethyl)azetidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-(4-(4-((6-(4-((2,6-dioxopiperidin-3-yl)amino)-2-fluorophenyl)- 2,6-diazaspiro[3.3]heptan-2-yl)methyl)piperidine-1-carbonyl)piperidine-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenoxy)piperidin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1S,4R)-4-(4-(3-((1S,4S)-5-(4-(2,6-dioxopiperidin-3- yl)phenyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)propyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)(methyl)amino)- 2-fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)piperazin-1-yl)methyl)piperidine-1-carbonyl)piperidine-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperidin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-(((R)-2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-(((S)-2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylatexylate; Ethyl 4-(((1S,4s)-4-(4-((1s,4S)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(2-fluoro-4-((1-methyl-2,6-dioxopiperidin-3- yl)amino)phenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)benzoyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2,6- difluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(4-(3-(2,4-dioxotetrahydropyrimidin-1(2H)- yl)-5-fluoro-1-methyl-1H-indazol-6-yl)piperazin-1-yl)ethyl)piperidine-1- carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H- pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)- 5-fluoro-1-methyl-1H-indazol-6-yl)piperazin-1-yl)methyl)piperidine-1- carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H- pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(3-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)azetidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin- 1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate;Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(1-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)-4-hydroxypiperidin-4-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-3- oxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1- oxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)-4-hydroxypiperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(5-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(3-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(4-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3- fluorophenyl)piperazin-1-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin- 1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((1-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperidin-4-yl)(methyl)amino)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate;Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(3-(4-(5-(2,6-dioxopiperidin-3-yl)pyridin-2- yl)piperazin-1-yl)propyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(5-((2,6-dioxopiperidin-3-yl)(methyl)amino)- 2-fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1R,4R)-4-((3R)-3-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(3-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)-3-fluoroazetidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(1-(1-(2-(4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)ethyl)piperidine-4-carbonyl)piperidine-4-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((1-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperidin-4-yl)oxy)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(3-(2-((S)-2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5- carbonyl)-3-azaspiro[5.5]undecan-9-yl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H- pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(3-(2-((S)-2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5- carbonyl)-3-azaspiro[5.5]undecan-9-yl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H- pyrazol-4-yl)amino)pyrimidine-5-carboxylate; 3-((3-Fluoro-4-(4-((1-((1R,4r)-4-(4-((1s,4S)-4-((6-methyl-5-(5-methyl-1,3,4- oxadiazol-2-yl)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4- yl)amino)cyclohexyl)piperazine-1-carbonyl)cyclohexane-1-carbonyl)piperidin-4- yl)methyl)piperazin-1-yl)phenyl)amino)piperidine-2,6-dione; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)-4-fluoropiperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)-1,1-difluoro-2-oxoethyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)-3,3-difluoropiperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((1-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)-4-hydroxypiperidin-4-yl)ethynyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1S,4R)-4-(4-(((3S)-1-(2-(2,6-dioxopiperidin-3-yl)-1- oxoisoindolin-5-yl)pyrrolidin-3-yl)methyl)piperazine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(1-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)-4-fluoropiperidin-4-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1S,4R)-4-((3S)-3-(2-(4-(4-((2,6-dioxopiperidin-3-yl)amino)- 2-fluorophenyl)piperazin-1-yl)ethyl)pyrrolidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-isopropyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(3-(2-(4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)ethyl)-3-fluoroazetidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Isopropyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazine-1-carbonyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo- 2,3-dihydro-1H-benzo[d]imidazol-5-yl)piperidin-1-yl)methyl)piperidine-1- carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H- pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(4-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2- oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)piperidin-1-yl)ethyl)piperidine-1- carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H- pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(1-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)-4-hydroxypiperidin-4-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-6-methyl-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-(((1r,4R)-4-(4-(4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazine-1-carbonyl)piperidine-1-carbonyl)cyclohexyl)methyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-6-((1-methyl-1H-pyrazol-4-yl)amino)nicotinate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(1-(2-fluoro-4-((1-methyl-2,6-dioxopiperidin- 3-yl)amino)phenyl)-4-hydroxypiperidin-4-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate;Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)-2-oxopiperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo- 2,3-dihydro-1H-benzo[d]imidazol-5-yl)piperazin-1-yl)methyl)piperidine-1- carbonyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H- pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-((4-((4-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2- oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)but-3-yn-1-yl)oxy)piperidin-1- yl)methyl)cyclohexane-1-carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H- pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(2-fluoro-4-((1-methyl-2,6-dioxopiperidin-3- yl)amino)phenyl)piperazin-1-yl)methyl)-4-hydroxypiperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((1-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)-4-hydroxypiperidin-4-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)oxy)-2- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(1-(4-(((S)-2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)-4-hydroxypiperidin-4-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(1-(4-(((R)-2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)-4-hydroxypiperidin-4-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate;Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-2,5- difluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-3- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(6-((2,6-dioxopiperidin-3- yl)carbamoyl)pyridin-3-yl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1s,4s)-4-(4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(6-((2,6-dioxopiperidin-3-yl)amino)pyridin- 3-yl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1-carbonyl)piperazin-1- yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5-carboxylate; 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylic acid; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((1-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)-4-fluoropiperidin-4-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate;Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)-3-oxopiperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-(2-(1-(4-((2,6-dioxopiperidin-3-yl)amino)-2- fluorophenyl)-4-methoxypiperidin-4-yl)ethyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; Ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2- oxopyridin-1(2H)-yl)piperidin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(4-((2,6-dioxopiperidin-3-yl)amino)-2,5- difluorophenyl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)oxy)-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidine-5- carboxylate; and ethyl 4-(((1S,4s)-4-(4-((1r,4R)-4-(4-((4-(5-((2,6-dioxopiperidin-3-yl)amino)-3- fluoropyridin-2-yl)piperazin-1-yl)methyl)piperidine-1-carbonyl)cyclohexane-1- carbonyl)piperazin-1-yl)cyclohexyl)amino)-2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidine-5-carboxylate; or a pharmaceutically acceptable salt thereof.

31. A pharmaceutical composition comprising a compound of any one of claims 1 to 30 and a pharmaceutically acceptable excipient.

32. The pharmaceutical composition of claim 31, wherein the pharmaceutically acceptable excipient is a carrier or diluent.

33. A method of treating or preventing from a disease, disorder or condition mediated by IRAK-3 in a subject comprising administering the subject in need thereof an effective amount of a compound of any one of claims 1 to 30.

34. The method of claim 33, wherein the disease, disorder or condition is a cancer.

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