STAT6 degrader compounds

Abstract

The present application provides heterocyclic compounds that modulate the activity of signal transducer and activator of transcription 6 (STAT6), which are useful in the treatment of various diseases, including cancer.

Description

[0001] 54057-0036W01 / SNV0027-W01 PATENT

[0002] STAT6 Degrader Compounds

[0003] TECHNICAE FIELD

[0004] The present disclosure provides heterocyclic compounds as well as their pharmaceutical compositions that modulate the activity of signal transducer and activator of transcription 6 (STAT6) and are useful in the treatment of various diseases related to STAT6, including cancer.

[0005] BACKGROUND

[0006] Signal transducer and activator of transcription 6 (STAT6) is a transcription factor that transmits signals from cytokines to the nucleus to regulate gene expression. This transcription factor controls expression of a variety of genes involved in allergic inflammation, immunity, and the development of B cells. Mounting evidence in humans and animal models demonstrate that the STAT6 signaling pathway plays a central role in controlling allergic inflammation (see e.g., Trends Immunol. 2024;45(2): 138-153).

[0007] Dysregulation of this pathway is involved in the pathogenesis of a set of allergic inflammatory diseases including atopic dermatitis, asthma, eosinophilic esophagitis, and food allergies etc., and multiple types of cancers.

[0008] SUMMARY

[0009] The present disclosure provides, inter alia, compounds of Formula 1-0:

[0010]

[0011] 1-0

[0012] or pharmaceutically acceptable salts thereof, wherein constituent members are defined herein.

[0013] The present disclosure further provides a pharmaceutical composition comprising a compound of the disclosure, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

[0014] The present disclosure further provides methods of inhibiting the signal transducer and activator of transcription 6 (STAT6) activity, comprising contacting the STAT6 with a compound described herein, or a pharmaceutically acceptable salt thereof.

[0015] The present disclosure further provides methods of treating a disease or a disorder associated with signal transducer and activator of transcription 6 (STAT6) in a patient by administering to the patient a therapeutically effective amount of a compound of the disclosure, or a pharmaceutically acceptable salt thereof.54057-0036W01 / SNV0027-W01 PATENT

[0016] The present disclosure further provides a compound described herein, or a pharmaceutically acceptable salt thereof, for use in any of the methods described herein.

[0017] The present disclosure further provides use of a compound described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for use in any of the methods described herein.

[0018] DETAILED DESCRIPTION

[0019] The present application provides a compound of Formula 1-0:

[0020]

[0021] 1-0

[0022] or a pharmaceutically acceptable salt thereof, wherein:

[0023] STAT6L is a STAT6 binding moiety selected from:

[0024]

[0025] 54057-0036W01 / SNV0027-W01 PATENT

[0026]

[0027] m, n, o, p, q, r, and t are each independently 0, 1, 2, 3, 4, 5, or 6;

[0028] each ~ is independently a single bond or double bond;

[0029] E3L is H or an E3 ubiquitin ligase binding moiety of formula E3L-1:

[0030]

[0031] E3L-1

[0032] X1is N or CR1;

[0033] X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12are each independently C orN; Y1, Y2, Y3, Y4, and Y5are each independently N, NH, N-RB, -O-, -S-, C=O, C(RB), or C(RB)2;

[0034] Z1, Z2, and Z3are each independently C or N;

[0035] W1and W2are independently selected from a bond, -C(O)-, -C(S)-, -S(O)2-, -S(O)-, -

[0036]

[0037] W3and W4are independently selected from a bond, -C(R°)2-, -O-, and -S-; orW3-W4is -CR°=CR°-;

[0038] each Rzis independently selected from H, halo, and

[0039]

[0040] ;54057-0036W01 / SNV0027-W01 PATENT

[0041]

[0042] Ring A is selected from C5-20 cycloalkyl, Ce-io aryl, 5-20 membered heterocycloalkyl, and 5-14 membered heteroaryl;

[0043] Ring B1, Ring B2, Ring B3, Ring B8, Ring B9, Ring B10, and Ring B11 are each independently selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-14 membered heteroaryl;

[0044] Ring B7 is selected from 14-membered heteroaryl and 14-20 membered heterocycloalkyl;

[0045] Ring Cl is selected from C9-14 cycloalkyl, 9-14 membered heterocycloalkyl, and 9-10 membered heteroaryl;

[0046] Ring C l 1 is selected from C4-14 cycloalkyl and 4-14 membered heterocycloalkyl; Ring C2, Ring C3, Ring C4, Ring C5, Ring C6, Ring C7, Ring C8, Ring C9, Ring CIO, and Ring C12 are each independently selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;

[0047] Ring D3 is selected from C12-30 cycloalkyl, 12-30 membered heterocycloalkyl, and 12-14 membered tricyclic heteroaryl;

[0048] Ring D8 is selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;

[0049] Ring D9, Ring E4, and Ring F 10 are each independently selected from C4-14 cycloalkyl and 4-14 membered heterocycloalkyl;

[0050] Ring

[0051]

[0052] is selected from C4-14 cycloalkyl and 4-14 membered heterocycloalkyl;

[0053] Ring E5 and Ring E6 are each independently selected from C5-14 cycloalkyl, Ce-io aryl, 5-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;

[0054] each Ring Z is independently selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;

[0055] L1is a bond or C1-3 alkylene, wherein 1-2 methylene groups of the C1-3 alkylene are each independently and optionally replaced by -O-, -S-, -N(RL1)-, -C(O)-, -N(RL1)C(O)-, -54057-0036W01 / SNV0027-W01 PATENT

[0056] N(RL1)C(O)N(RL1)-, -N(RL1)C(O)O-, -S(O)-, -S(O)2-, -S(O)(=NRL1)-, -S(O)2N(RL1)-, and -N(RL1)S(O)2N(RL1)-, and wherein the C1-3 alkylene of L1is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;

[0057] each RL1is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;

[0058] L is a bond or C1-20 alkylene, wherein 1-10 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, -N(R)S(O)2N(R)-, -C(RO)2-, -C(R°)=C(R0)-, -C=C-, or -Cy-;

[0059] each -Cy- is independently selected from C3-30 cycloalkyl, Ce-io aryl, 4-30 membered heterocycloalkyl, and 5-14 membered heteroaryl, wherein the C3-30 cycloalkyl, Ce-io aryl, 4-30 membered heterocycloalkyl, and 5-14 membered heteroaryl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0060] Lc, LD, and LFare each independently selected from a bond and C1-6 alkylene, wherein 1-3 methylene groups of the C1-6 alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, -N(R)S(O)2N(R)-, -C(R°)=C(R0)-, -C=C-, or -Cy-, wherein the C1-6 alkylene of Lc, LD, and LFis optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0061] LBis Ci -10 alkylene, wherein 1-6 methylene groups of the Ci.10 alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, or -N(R)S(O)2N(R)-, wherein the Ci.10 alkylene ofLBis optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0062] LBDis Ci -10 alkylene, wherein 1-6 methylene groups of the CMO alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, -N(R)S(O)2N(R)-, -C(RO)2-, or -Cy-;

[0063] R1is selected from H, D, halo, CN, C1-4 alkyl, Ci -4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

[0064] or, R1and one of RA, together with the atoms to which they are attached, form a C5-10 cycloalkyl, or 5-10 membered heterocycloalkyl group, wherein the C5-10 cycloalkyl, and 5-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0065] or, R1and L1, together with the atoms to which they are attached, form a C3-10 cycloalkyl, or 4-10 membered heterocycloalkyl group, wherein the C3-10 cycloalkyl, and 4-1054057-0036W01 / SNV0027-W01 PATENT

[0066] membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0067] each RA, RB, Rc, RD, RE, RF, and Rzois independently selected from H, halo, Ci-6 alkyl, Ci-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -OR, -SF5, -SR, -NRR, -NRNR2, -NO2, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NRNR2, -C(O)NR(OR), -OC(O)R, -OC(O)NR2, -OC(O)OR, -OS(O)2R, -OS(O)2NR2, -NRC(O)R, -NRC(O)OR, -NRC(O)NR2, -NRS(O)2R, -NRS(O)2NR2, -NROR, -NRS(O)R, -NRS(O)NR2, -S(O)R, -S(O)2R, -S(O)NR2, -S(O)2NR2, -C(=NR)R, -C(=NR)NR2, -NRC(=NR)R, -NRC(=NR)NR2, -NRS(O)(=NR)R, -NRS(O)(=NR)NR2, =NR, -N=S(O)R2, -N=S(O)RNR2, -OS(O)(=NR)R, -S(O)(=NR)R, -S(O)(=NR)NR2, -C(O)NRS(O)2R, -C(O)NRS(O)2NR2, -S(O)2NRC(O)R, -NRS(O)NRC(O)R, and -P(O)RR, wherein the Ci6alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0068] or, two REgroups, together with the atoms to which they are attached, form a C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, or 5-10 membered heteroaryl group, wherein the C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0069] each R, R9A, R9B, R10A, R10B, R11A, R11B, R12A, and R12Bis independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0070] or, two R groups attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;54057-0036W01 / SNV0027-W01 PATENT

[0071] each R° is independently selected from H, halo, Ci-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa0, -SF5, -SRa0, -NRc0Rd0, -NRc0NRc0Rd0, -NO2, -C(O)Ra0, -C(O)ORa0, -C(O)NRc0Rd0, -C(O)NRc0NRc0Rd0, -C(O)NRc0(ORa0), -OC(O)Ra0, -OC(O)NRc0Rd0, -OC(O)ORa0, -OS(O)2Rb0, -OS(O)2NRc0Rd0, -NRc0C(O)Ra0, -NRc0C(O)ORa0, -NRc0C(O)NRc0Rd0, -NRc0S(O)2Rb0, -NRc0S(O)2NRc0Rd0, -NRc0ORa0, -NRc0S(O)Rb0, -NRc0S(O)NRc0Rd0, -S(O)Rb0, -S(O)2Rb0, -S(O)NRc0Rd0, -S(O)2NRc0Rd0, -C(=NRe0)Ra0, -C(=NRe0)NRc0Rd0, -NRc0C(=NRe0)Ra0, -NRc0C(=NRe0)NRc0Rd0, -NRc0S(O)(=NRe0)Rb0, -NRc0S(O)(=NRe0)NRc0Rd0, =NRe0, -N=S(O)(Rb0)2, -N=S(O)Rb0NRc0Rd0, -OS(O)(=NRe0)Rb0, -S(O)(=NRe0)Rb0, -S(O)(=NRe0)NRc0Rd0, -C(O)NRc0S(O)2Rb0, -C(O)NRc0S(O)2NRc0Rd0, -S(O)2NRc0C(O)Rb0, -NRc0S(O)NRc0C(O)Rb0, and -P(O)Rf0Rg0, wherein the C1-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R° are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;

[0072] each Ra0, Rc0, and Rd0is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra0, Rc0, and Rd0are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;

[0073] or, any Rc0and Rd0attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;

[0074] each Rb0is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl,54057-0036W01 / SNV0027-W01 PATENT

[0075] (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb0are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;

[0076] each Re0is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;

[0077] each Rf0and Rg0are independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;

[0078] each R0Ais independently selected from H, halo, C1-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa°A _S_SRaOA5_NRc0ARd0A _NRc°ANRc0ARd0A, _NQ2, -C(O)Ra0A, -C(O)ORa°A, -C(O)NRc0ARd0A, -C(O)NRc0ANRc0ARd0A, -C(O)NRc0A(ORa0A), -OC(O)Ra0A, -OC(O)NRc0ARd0A, -OC(O)ORa0A, -OS(O)2Rb0A, -OS(O)2NRc0ARd0A, -NRc0AC(O)Ra0A, -NRc0AC(O)ORa0A, -NRc0AC(O)NRc0ARd0A, -NRc0AS(O)2Rb0A, -NRc0AS(O)2NRc0ARd0A, -NRc0AORa0A, -NRc0AS(O)Rb0A, -NRc0AS(O)NRc0ARd0A, -S(O)Rb0A, -S(O)2Rb0A, -S(O)NRc0ARd0A, -S(O)2NRc0ARd0A, -C(=NRe0A)Ra0A, -C(=NRe0A)NRc0ARd0A, -NRc0AC(=NRe0A)Ra0A, -NRc0AC(=NRe0A)NRc0ARd0A, -NRc0AS(O)(=NRe0A)Rb0A, -NRc0AS(O)(=NRe0A)NRc0ARd0A, =NRe0A, -N=S(O)(Rb0A)2, -N=S(O)Rb0ANRc0ARd0A, -OS(O)(=NRe0A)Rb0A, -S(O)(=NRe0A)Rb0A, -S(O)(=NRe0A)NRc0ARd0A, -C(O)NRc0AS(O)2Rb0A, -C(O)NRc0AS(O)2NRc0ARd0A, -S(O)2NRc0AC(O)Rb0A, -NRc0AS(O)NRc0AC(O)Rb0A, and -P(O)RfflARg0A, wherein the Ci-6alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R0Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;

[0079] each Ra0A, Rc0A, and Rd0Ais independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-654057-0036W01 / SNV0027-W01 PATENT

[0080] alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra0A, Rc0A, and Rd0Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;

[0081] or, any Rc0Aand Rd0Aattached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;

[0082] each Rb0Ais independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb0Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;

[0083] each Re0Ais independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;

[0084] each Rf0Aand Rg0Aare independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;

[0085] each R0Bis independently selected from H, halo, C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -

[0086]

[0087] 54057-0036W01 / SNV0027-W01 PATENT

[0088] NRc0BS(O)Rb0B, -NRc0BS(O)NRc0BRd0B, -S(O)Rb0B, -S(O)2Rb0B, -S(O)NRc0BRd0B, -S(O)2NRc0BRd0B, -C(=NRe0B)Ra0B, -C(=NRe0B)NRc0BRd0B, -NRc0BC(=NRe0B)Ra0B, -NRc0BC(=NRe0B)NRc0BRd0B, -NRc0BS(O)(=NRe0B)Rb0B, -NRc0BS(O)(=NRe0B)NRc0BRd0B, -OS(O)(=NRe0B)Rb0B, -S(O)(=NRe0B)Rb0B, -S(O)(=NRe0B)NRc0BRd0B, -C(O)NRc0BS(O)2Rb0B, -C(O)NRc0BS(O)2NRc0BRd0B, -S(O)2NRc0BC(O)Rb0B, -NRc0BS(O)NRc0BC(O)Rb0B, and -P(O)Rf0BRg0B, wherein the Ci-6 alkyl, Ci-6 alkylidenyl, C2.6 alkenyl, C2.6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R0Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;

[0089] each Ra0B, Rc0B, and Rd0Bis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2.6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra0B, Rc0B, and Rd0Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;

[0090] or, any Rc0Band Rd0Battached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;

[0091] each Rb0Bis independently selected from C1-6 alkyl, C1-6 haloalkyl, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb0Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;

[0092] each Re0Bis independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-54057-0036W01 / SNV0027-W01 PATENT

[0093] Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;

[0094] each Rf0Band Rg0Bare independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; and

[0095] each RGis independently selected from H, OH, CN, halo, C1-4 alkyl, Ci-4alkylidenyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-Ci.4 alkyl, HO-C1.4 alkyl, C1-4 alkoxy-Ci.4 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, C1-3 alkylthio, C1-3 alkylsulfmyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, aminocarbonyloxy, C1-3 alkylaminocarbonyloxy, di(Ci-3 alkyl)aminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(Ci-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(Ci-3 alkyl)aminocarbonylamino.

[0096] In some embodiments, the present application provides a compound of Formula I:

[0097]

[0098] I

[0099] or a pharmaceutically acceptable salt thereof, wherein:

[0100] STAT6L is a STAT6 binding moiety selected from:

[0101]

[0102] 54057-0036W01 / SNV0027-W01 PATENT

[0103]

[0104] m, n, o, p, q, r, and t are each independently 0, 1, 2, 3, 4, 5, or 6;

[0105] each ~ is independently a single bond or double bond;

[0106] X1is N or CR1;

[0107] X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12are each independently C orN; Y1, Y2, Y3, Y4, and Y5are each independently N, NH, N-RB, -O-, -S-, C=O, C(RB), or C(RB)2;

[0108] Z1, Z2, and Z3are each independently C or N;

[0109] each Rzis independently selected from H, halo, and

[0110]

[0111] 54057-0036W01 / SNV0027-W01 PATENT

[0112]

[0113] Ring A is selected from C5-20 cycloalkyl, Ce-io aryl, 5-20 membered heterocycloalkyl, and 5-14 membered heteroaryl;

[0114] Ring B1, Ring B2, Ring B3, Ring B8, Ring B9, Ring B10, and Ring B11 are each independently selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-14 membered heteroaryl;

[0115] Ring B7 is selected from 14-membered heteroaryl and 14-20 membered heterocycloalkyl;

[0116] Ring Cl is selected from C9-14 cycloalkyl, 9-14 membered heterocycloalkyl, and 9-10 membered heteroaryl;

[0117] Ring C l 1 is selected from C4-14 cycloalkyl and 4-14 membered heterocycloalkyl; Ring C2, Ring C3, Ring C4, Ring C5, Ring C6, Ring C7, Ring C8, Ring C9, Ring CIO, and Ring C12 are each independently selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;

[0118] Ring D3 is selected from C12-20 cycloalkyl, 12-20 membered heterocycloalkyl, and 12-14 membered tricyclic heteroaryl;

[0119] Ring D8 is selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;

[0120] Ring D9, Ring E4, and Ring F 10 are each independently selected from C4-14 cycloalkyl and 4-14 membered heterocycloalkyl;

[0121] Ring

[0122]

[0123] is selected from C4-14 cycloalkyl and 4-14 membered heterocycloalkyl;

[0124] Ring E5 and Ring E6 are each independently selected from C5-14 cycloalkyl, Ce-io aryl, 5-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;

[0125] each Ring Z is independently selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;

[0126] L1is a bond or C1-3 alkylene, wherein 1-2 methylene groups of the C1-3 alkylene are each independently and optionally replaced by -O-, -S-, -N(RL1)-, -C(O)-, -N(RL1)C(O)-, -54057-0036W01 / SNV0027-W01 PATENT

[0127] N(RL1)C(O)N(RL1)-, -N(RL1)C(O)O-, -S(O)-, -S(O)2-, -S(O)(=NRL1)-, -S(O)2N(RL1)-, and -N(RL1)S(O)2N(RL1)-, and wherein the C1-3 alkylene of L1is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;

[0128] each RL1is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;

[0129] L is a bond or C1-20 alkylene, wherein 1-10 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, -N(R)S(O)2N(R)-, -C(RO)2-, -C(R°)=C(R0)-, -C=C-, or -Cy-;

[0130] each -Cy- is independently selected from C3-20cycloalkyl, Ce-io aryl, 4-20 membered heterocycloalkyl, and 5-14 membered heteroaryl, wherein the C3-20cycloalkyl, C6-10aryl, 4-20 membered heterocycloalkyl, and 5-14 membered heteroaryl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0131] Lc, LD, and LFare each independently selected from a bond and C1-6 alkylene, wherein 1-3 methylene groups of the C1-6 alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, -N(R)S(O)2N(R)-, -C(R°)=C(R0)-, -C=C-, or -Cy-, wherein the C1-6 alkylene of Lc, LD, and LFis optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0132] LBis Ci -10 alkylene, wherein 1-6 methylene groups of the Ci.10 alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, or -N(R)S(O)2N(R)-, wherein the Ci.10 alkylene ofLBis optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0133] LBDis Ci -10 alkylene, wherein 1-6 methylene groups of the CMO alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, -N(R)S(O)2N(R)-, -C(RO)2-, or -Cy-;

[0134] R1is selected from H, D, halo, CN, C1-4 alkyl, Ci -4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;

[0135] each RA, RB, Rc, RD, RE, RF, and Rzois independently selected from H, halo, C1-6 alkyl, C1-6 alkylidenyl, C2-6alkenyl, C2-6alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -OR, -SF5, -SR, -NRR, -NO2, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NR(OR), -OC(O)R, -OC(O)NR2, -OC(O)OR, -OS(O)2R, -OS(O)2NR2, -NRC(O)R, -NRC(O)OR, -NRC(O)NR2, -NRS(O)2R, -NRS(O)2NR2, -NROR, -NRS(O)R, -NRS(O)NR2, -S(O)R, -54057-0036W01 / SNV0027-W01 PATENT

[0136] S(O)2R, -S(O)NR2, -S(O)2NR2, -C(=NR)R, -C(=NR)NR2, -NRC(=NR)R, -NRC(=NR)NR2, -NRS(O)(=NR)R, -NRS(O)(=NR)NR2, =NR, -N=S(O)R2, -N=S(O)RNR2, -OS(O)(=NR)R, -S(O)(=NR)R, -S(O)(=NR)NR2, -C(O)NRS(O)2R, -C(O)NRS(O)2NR2, -S(O)2NRC(O)R, -NRS(O)NRC(O)R, and -P(O)RR, wherein the Ci-6 alkyl, Ci-6 alkylidenyl, C2.6 alkenyl, C2.6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0137] or, two REgroups, together with the atoms to which they are attached, form a C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, or 5-10 membered heteroaryl group, wherein the C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0138] each R, R9A, R9B, R10A, R10B, R11A, R11B, R12A, and R12Bis independently selected from H, C1-6 alkyl, C2.6 alkenyl, C2.6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2.6 alkenyl, C2.6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0139] or, two R groups attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0140] each R° is independently selected from H, halo, C1-6 alkyl, Ci -6 alkylidenyl, C2.6 alkenyl, C2.6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa0, -SF5, -SRa0, -NRc0Rd0, -NO2, -C(O)Ra0, -C(O)ORa0, -C(O)NRc0Rd0, -C(O)NRc0(ORa0), -OC(O)Ra0, -OC(O)NRc0Rd0, -OC(O)ORa0, -OS(O)2Rb0, -OS(O)2NRc0Rd0, -NRc0C(O)Ra0, -NRc0C(O)ORa0, -NRc0C(O)NRc0Rd0, -NRc0S(O)2Rb0, -NRc0S(O)2NRc0Rd0, -NRc0ORa0, -NRc0S(O)Rb0, -NRc0S(O)NRc0Rd0, -S(O)Rb0, -S(O)2Rb0, -S(O)NRc0Rd0, -S(O)2NRc0Rd0, -C(=NRe0)Ra0, -C(=NRe0)NRc0Rd0, -NRc0C(=NRe0)Ra0, -NRc0C(=NRe0)NRc0Rd0, -NRc0S(O)(=NRe0)Rb0, -NRc0S(O)(=NRe0)NRc0Rd0, =NRe0, -N=S(O)(Rb0)2, -54057-0036W01 / SNV0027-W01 PATENT

[0141] N=S(O)Rb0NRc0Rd0, -OS(O)(=NRe0)Rb0, -S(O)(=NRe0)Rb0, -S(O)(=NRe0)NRc0Rd0, -C(O)NRc0S(O)2Rb0, -C(O)NRc0S(O)2NRc0Rd0, -S(O)2NRc0C(O)Rb0, -NRc0S(O)NRc0C(O)Rb0, and -P(O)Rf0Rg0, wherein the Ci-6 alkyl, Ci-6 alkylidenyl, C2.6 alkenyl, C2.6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R° are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;

[0142] each Ra0, Rc0, and Rd0is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2.6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra0, Rc0and Rd0are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;

[0143] or, any Rc0and Rd0attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;

[0144] each Rb0is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb0are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;

[0145] each Re0is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;

[0146] each Rf0and Rg0are independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-1054057-0036W01 / SNV0027-W01 PATENT

[0147] membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;

[0148] each R0Ais independently selected from H, halo, C1-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -

[0149]

[0150] NRc0AS(O)NRc0AC(O)Rb0A, and -P(O)Rf0ARg0A, wherein the Ci-6alkyl, Ci-ealkylidenyl, C2-6alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R0Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;

[0151] each Ra0A, Rc0A, and Rd0Ais independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra0A, Rc0A, and Rd0Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;

[0152] or, any Rc0Aand Rd0Aattached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;54057-0036W01 / SNV0027-W01 PATENT

[0153] each Rb0Ais independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb0Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;

[0154] each Re0Ais independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;

[0155] each Rf0Aand Rg0Aare independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;

[0156] each R0Bis independently selected from H, halo, C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa0B, -SF5, -SRa0B, -NRc0BRd0B, -NO2, -C(O)Ra0B, -C(O)ORa0B, -C(O)NRc0BRd0B, -C(O)NRc0B(ORa0B), -OC(O)Ra0B, -OC(O)NRc0BRd0B, -OC(O)ORa0B, -OS(O)2Rb0B, -OS(O)2NRc0BRd0B, -NRc0BC(O)Ra0B, -NRc0BC(O)ORa0B, -NRc0BC(O)NRc0BRd0B, -NRc0BS(O)2Rb0B, -NRc0BS(O)2NRc0BRd0B, -NRc0BORa0B, -NRc0BS(O)Rb0B, -NRc0BS(O)NRc0BRd0B, -S(O)Rb0B, -S(O)2Rb0B, -S(O)NRc0BRd0B, -S(O)2NRc0BRd0B, -C(=NRe0B)Ra0B, -C(=NRe0B)NRc0BRd0B, -NRc0BC(=NRe0B)Ra0B, -NRc0BC(=NRe0B)NRc0BRd0B, -NRc0BS(O)(=NRe0B)Rb0B, -NRc0BS(O)(=NRe0B)NRc0BRd0B, -OS(O)(=NRe0B)Rb0B, -S(O)(=NRe0B)Rb0B, -S(O)(=NRe0B)NRc0BRd0B, -C(O)NRc0BS(O)2Rb0B, -C(O)NRc0BS(O)2NRc0BRd0B, -S(O)2NRc0BC(O)Rb0B, -NRc0BS(O)NRc0BC(O)Rb0B, and -P(O)Rf0BRg0B, wherein the C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered54057-0036W01 / SNV0027-W01 PATENT

[0157] heterocycloalkyl) -Ci.4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R0Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;

[0158] each Ra0B, Rc0B, and Rd0Bis independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra0B, Rc0B, and Rd0Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;

[0159] or, any Rc0Band Rd0Battached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;

[0160] each Rb0Bis independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb0Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;

[0161] each Re0Bis independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;

[0162] each Rf0Band Rg0Bare independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; and

[0163] each RGis independently selected from H, OH, CN, halo, C1-4 alkyl, Ci-4alkylidenyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-Ci.4 alkyl, HO-C1.4 alkyl, C1-4 alkoxy-Ci.454057-0036W01 / SNV0027-W01 PATENT

[0164] alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, C1-3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, aminocarbonyloxy, C1-3 alkylaminocarbonyloxy, di(Ci-3 alkyl)aminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(Ci-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(Ci-3 alkyl)aminocarbonylamino.

[0165] In some embodiments, the present application provides a compound of Formula I:

[0166]

[0167] I

[0168] or a pharmaceutically acceptable salt thereof, wherein:

[0169] STAT6L is a STAT6 binding moiety selected from:

[0170]

[0171] 54057-0036W01 / SNV0027-W01 PATENT

[0172]

[0173] m, n, o, p, q, r, and t are each independently 0, 1, 2, 3, 4, 5, or 6;

[0174] each ~ is independently a single bond or double bond;

[0175] X1is N or CR1;

[0176] X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12are each independently C orN; Y1, Y2, Y3, Y4, and Y5are each independently N, NH, N-RB, -O-, -S-, C=O, C(RB), or C(RB)2;

[0177] Z1, Z2, and Z3are each independently C or N;

[0178] each Rzis independently selected from H, halo, and

[0179]

[0180]

[0181] 54057-0036W01 / SNV0027-W01 PATENT

[0182] Ring A is selected from C5-14 cycloalkyl, Ce-io aryl, 5-14 membered heterocycloalkyl, and 5-14 membered heteroaryl;

[0183] Ring B1, Ring B2, Ring B3, Ring B8, Ring B9, Ring B10, and Ring B11 are each independently selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-14 membered heteroaryl;

[0184] Ring B7 is selected from 14-membered heteroaryl and 14-20 membered heterocycloalkyl;

[0185] Ring C1 is selected from C9-14 cycloalkyl, 9-14 membered heterocycloalkyl, and 9-10 membered heteroaryl;

[0186] Ring C11 is selected from C4-14 cycloalkyl and 4-14 membered heterocycloalkyl; Ring C2, Ring C3, Ring C4, Ring C5, Ring C6, Ring C7, Ring C8, Ring C9, Ring CIO, and Ring C12 are each independently selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;

[0187] Ring D3 is selected from C12-20 cycloalkyl, 12-20 membered heterocycloalkyl, and 12-14 membered tricyclic heteroaryl;

[0188] Ring D8 is selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;

[0189] Ring D9, Ring E4, and Ring F 10 are each independently selected from C4-14 cycloalkyl and 4-14 membered heterocycloalkyl;

[0190] Ring

[0191]

[0192] is selected from C4-14 cycloalkyl and 4-14 membered heterocycloalkyl;

[0193] Ring E5 and Ring E6 are each independently selected from C5-14 cycloalkyl, Ce-io aryl, 5-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;

[0194] each Ring Z is independently selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;

[0195] L1is a bond or C1-3 alkylene, wherein 1-2 methylene groups of the C1-3 alkylene are each independently and optionally replaced by -O-, -S-, -N(RL1)-, -C(O)-, -N(RL1)C(O)-, -N(RL1)C(O)N(RL1)-, -N(RL1)C(O)O-, -S(O)-, -S(O)2-, -S(O)(=NRL1)-, -S(O)2N(RL1)-, and -N(RL1)S(O)2N(RL1)-, and wherein the C1-3 alkylene of L1is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;

[0196] each RL1is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;

[0197] L is a bond or C1-20 alkylene, wherein 1-10 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -54057-0036W01 / SNV0027-W01 PATENT

[0198] N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, -N(R)S(O)2N(R)-, -C(RO)2-, or -Cy-;

[0199] each -Cy- is independently selected from C3-20cycloalkyl, Ce-io aryl, 4-20 membered heterocycloalkyl, and 5-14 membered heteroaryl, wherein the C3-20cycloalkyl, C6-10aryl, 4-20 membered heterocycloalkyl, and 5-14 membered heteroaryl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0200] Lc, LD, and LFare each independently selected from a bond and Ci-6 alkylene, wherein 1-3 methylene groups of the Ci-6 alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, or -N(R)S(O)2N(R)-, wherein the Ci-6alkylene of Lc, LD, and LFis optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0201] LBis Ci -io alkylene, wherein 1-6 methylene groups of the C O alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, or -N(R)S(O)2N(R)-, wherein the CMO alkylene ofLBis optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0202] LBDis Ci -io alkylene, wherein 1-6 methylene groups of the C O alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, -N(R)S(O)2N(R)-, -C(RO)2-, or -Cy-;

[0203] R1is selected from H, D, halo, CN, Ci-4 alkyl, Ci.4haloalkyl, CM alkoxy, and CM haloalkoxy;

[0204] each RA, RB, Rc, RD, RE, RF, and Rzois independently selected from H, halo, CM alkyl, Ci-6 alkylidenyl, C2.6 alkenyl, C2.ealkynyl, CM haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci.4 alkyl, Ce-io aryl-Ci.4 alkyl, (4-10 membered heterocycloalkyl) -CM alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -OR, -SF5, -SR, -NRR, -NO2, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NR(OR), -OC(O)R, -OC(O)NR2, -OC(O)OR, -OS(O)2R, -OS(O)2NR2, -NRC(O)R, -NRC(O)OR, -NRC(O)NR2, -NRS(O)2R, -NRS(O)2NR2, -NROR, -NRS(O)R, -NRS(O)NR2, -S(O)R, -S(O)2R, -S(O)NR2, -S(O)2NR2, -C(=NR)R, -C(=NR)NR2, -NRC(=NR)R, -NRC(=NR)NR2, -NRS(O)(=NR)R, -NRS(O)(=NR)NR2, -OS(O)(=NR)R, -S(O)(=NR)R, -S(O)(=NR)NR2, -C(O)NRS(O)2R, -C(O)NRS(O)2NR2, -S(O)2NRC(O)R, -NRS(O)NRC(O)R, and -P(O)RR, wherein the CM alkyl, Ci- 6 alkylidenyl, CM alkenyl, C alkynyl, CM haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci.4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and54057-0036W01 / SNV0027-W01 PATENT

[0205] (5-10 membered heteroaryl)-Ci-4 alkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0206] or, two REgroups, together with the atoms to which they are attached, form a C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, or 5-10 membered heteroaryl group, wherein the C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0207] each R, R9A, R9B, R10A, R10B, R11A, R11B, R12A, and R12Bis independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0208] or, two R groups attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0209] each R° is independently selected from H, halo, C1-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa0, -SF5, -SRa0, -NRc0Rd0, -NO2, -C(O)Ra0, -C(O)ORa0, -C(O)NRc0Rd0, -C(O)NRc0(ORa0), -OC(O)Ra0, -OC(O)NRc0Rd0, -OC(O)ORa0, -OS(O)2Rb0, -OS(O)2NRc0Rd0, -NRc0C(O)Ra0, -NRc0C(O)ORa0, -NRc0C(O)NRc0Rd0, -NRc0S(O)2Rb0, -NRc0S(O)2NRc0Rd0, -NRc0ORa0, -NRc0S(O)Rb0, -NRc0S(O)NRc0Rd0, -S(O)Rb0, -S(O)2Rb0, -S(O)NRc0Rd0, -S(O)2NRc0Rd0, -C(=NRe0)Ra0, -C(=NRe0)NRc0Rd0, -NRc0C(=NRe0)Ra0, -NRc0C(=NRe0)NRc0Rd0, -NRc0S(O)(=NRe0)Rb0, -NRc0S(O)(=NRe0)NRc0Rd0, -OS(O)(=NRe0)Rb0, -S(O)(=NRe0)Rb0, -S(O)(=NRe0)NRc0Rd0, -C(O)NRc0S(O)2Rb0, -C(O)NRc0S(O)2NRc0Rd0, -S(O)2NRc0C(O)Rb0, -NRc0S(O)NRc0C(O)Rb0, and -P(O)Rf0Rg0, wherein the C1-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R° are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;54057-0036W01 / SNV0027-W01 PATENT

[0210] each Ra0, Rc0, and Rd0is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra0, Rc0and Rd0are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;

[0211] or, any Rc0and Rd0attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;

[0212] each Rb0is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb0are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;

[0213] each Re0is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;

[0214] each Rf0and Rg0are independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;

[0215] each R0Ais independently selected from H, halo, C1-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -54057-0036W01 / SNV0027-W01 PATENT

[0216]

[0217] C(O)NRc0AS(O)2NRc0ARd0A, -S(O)2NRc0AC(O)Rb0A, -NRc0AS(O)NRc0AC(O)Rb0A, and -P(O)Rf0ARg0A, wherein the Ci-6 alkyl, Ci-ealkylidenyl, C2.6 alkenyl, C2.6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R0Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;

[0218] each Ra0A, Rc0A, and Rd0Ais independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2.6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra0A, Rc0A, and Rd0Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;

[0219] or, any Rc0Aand Rd0Aattached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;

[0220] each Rb0Ais independently selected from C1-6 alkyl, C1-6 haloalkyl, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb0Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;54057-0036W01 / SNV0027-W01 PATENT

[0221] each Re0Ais independently selected from H, OH, CN, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;

[0222] each Rf0Aand Rg0Aare independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;

[0223] each R0Bis independently selected from H, halo, C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -

[0224]

[0225] C(O)NRc0BS(O)2NRc0BRd0B, -S(O)2NRc0BC(O)Rb0B, -NRc0BS(O)NRc0BC(O)Rb0B, and -P(O)Rf0BRg0B, wherein the C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R0Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;

[0226] each Ra0B, Rc0B, and Rd0Bis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of54057-0036W01 / SNV0027-W01 PATENT

[0227] Ra0B, Rc0B, and Rd0Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;

[0228] or, any Rc0Band Rd0Battached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;

[0229] each Rb0Bis independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb0Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;

[0230] each Re0Bis independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;

[0231] each Rf0Band Rg0Bare independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; and

[0232] each RGis independently selected from H, OH, CN, halo, C1-4 alkyl, Ci-4alkylidenyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-Ci.4 alkyl, HO-C1.4 alkyl, C1-4 alkoxy-Ci.4 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, C1-3 alkylthio, C1-3 alkylsulfmyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, aminocarbonyloxy, C1-3 alkylaminocarbonyloxy, di(Ci-3 alkyl)aminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(Ci-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(Ci-3 alkyl)aminocarbonylamino.54057-0036W01 / SNV0027-W01 PATENT In some embodiments, STAT6L is a STAT6 binding moiety selected from

[0233]

[0234] 54057-0036W01 / SNV0027-W01 PATENT

[0235]

[0236] STAT6L-12A

[0237] wherein refers to the bond between STAT6L and L.

[0238] In some embodiments, STAT6L is a STAT6 binding moiety selected from

[0239]

[0240] STAT6L-4B STAT6L-5A54057-0036W01 / SNV0027-W01 PATENT

[0241]

[0242] wherein •~ ww- refers to the bond between STAT6L and L.

[0243] In some embodiments, STAT6L is a STAT6 binding moiety selected from

[0244]

[0245] wherein ■ / www' refers to the bond between STAT6L and L.

[0246] In some embodiments, Ring Cl is 9-14 membered heterocycloalkyl.54057-0036W01 / SNV0027-W01 PATENT

[0247] In some embodiments, Ring Cl is selected from l,5,8,8a-tetrahydroimidazo[l,5-a]pyridin-3(2H)-onyl, 5,8-dihydro-[l,2,4]triazolo[4,3-a]pyridinyl, and 2,7-diazaspiro [4.5] decan- 1 -onyl.

[0248] In some embodiments, Ring C 1 is selected from

[0249]

[0250]

[0251] In some embodiments, Ring Bl is 5-14 membered heteroaryl.

[0252] In some embodiments, Ring Bl is 8-10 membered heteroaryl.

[0253] In some embodiments, Ring Bl is indolyl.

[0254] In some embodiments, Ring B2 is 5-14 membered heteroaryl.

[0255] In some embodiments, Ring B2 is 8-10 membered heteroaryl.

[0256] In some embodiments, Ring B2 is indolyl.

[0257] In some embodiments, Ring C3 is 4-14 membered heterocycloalkyl or 5-10 membered heteroaryl.

[0258] In some embodiments, Ring C3 is 4-14 membered heterocycloalkyl or 5-6 membered heteroaryl.

[0259] In some embodiments, Ring C3 is 4-7 membered heterocycloalkyl or 5-6 membered heteroaryl.

[0260] In some embodiments, Ring C3 is 5-10 membered heteroaryl.

[0261] In some embodiments, Ring C3 is 5-6 membered heteroaryl.

[0262] In some embodiments, Ring C3 is 4-14 membered heterocycloalkyl.

[0263] In some embodiments, Ring C3 is 4-7 membered heterocycloalkyl.

[0264] In some embodiments, Ring C3 is selected from pyridinyl, 1, 2,3,6-tetrahydropyridinyl, 5 -azaspiro [3.5]non-7-eneyl, 8-azabicyclo[3.2.1]oct-2-eneyl, 6-azaspiro[3.5]non-8-eneyl, 1,2-dihydroquinolinyl, 9-azabicyclo[4.2. l]non-2-eneyl, 2,4a,5,6,7,7a-hexahydro-lH-cyclopenta[b]pyridinyl, 6-azaspiro[3.5]nonanyl, and piperidinyl.

[0265] In some embodiments, Ring C3 is selected from 1,2,3,6-tetrahydropyridinyl, 5-azaspiro[3.5]non-7-eneyl, 8-azabicyclo[3.2.1]oct-2-eneyl, 6-azaspiro[3.5]non-8-eneyl, 1,2-dihydroquinolinyl, 9 -azabicyclo [4.2. l]non-2-eneyl, 2,4a,5,6,7,7a-hexahydro-lH-cyclopenta[b]pyridinyl, 6-azaspiro[3.5]nonanyl, and piperidinyl.54057-0036W01 / SNV0027-W01 PATENT

[0266] In some embodiments, Ring C3 is selected from 1,2,3,6-tetrahydropyridinyl, 5-azaspiro[3.5]non-7-eneyl, (lS,5R)-8-azabicyclo[3.2. l]oct-2-eneyl, 6-azaspiro[3.5]non-8-eneyl, 1,2-dihydroquinolinyl, 9-azabicyclo[4.2.1]non-2-eneyl, 2,4a,5,6,7,7a-hexahydro-lH-cyclopenta[b]pyridinyl, 6-azaspiro[3.5]nonanyl, and piperidinyl.

[0267] In some embodiments, Ring C3 is 1,2,3,6-tetrahydropyridinyl.

[0268] In some embodiments, Ring B3 is 5-14 membered heteroaryl.

[0269] In some embodiments, Ring B3 is 8-10 membered heteroaryl.

[0270] In some embodiments, Ring B3 is indolyl.

[0271] In some embodiments, Ring D3 is 12-30 membered heterocycloalkyl.

[0272] In some embodiments, Ring D3 is 12-20 membered heterocycloalkyl.

[0273] In some embodiments, Ring D3 is 12-16 membered heterocycloalkyl.

[0274] In some embodiments, Ring D3 is selected from

[0275] 6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[l,2-d][l,4]oxazinyl, 2,3-dihydrospiro[indene- 1,4'-piperidinyl], 1,2,3,4, 4a, 5 -hexahydrobenzo [b]pyrazino [1,2-d] [l,4]oxazinyl, 2,3-dihydrospiro[indene-l,3'-pyrrolidinyl], 3 H-spiro [isobenzofuran- 1,4'-piperidinyl], spiro[indoline-3,4'-piperidin]-2-onyl, spiro[indoline-3,4'-piperidinyl], 3H-spiro [isobenzofuran- 1,4'-piperidin] -3 -onyl, spiro [isoindoline- 1,4'-piperidinyl], 2-(methylimino)-2,3-dihydro-216-spiro[benzo[c]thiophene-l,4'-piperidinyl] 2-oxide, 2H-spiro [benzofuran-3,4'-piperidinyl], 2,3 -dihydrospiro [indene- 1,4'-piperidinyl], 1,2,3,4,4a, 5 -hexahydrobenzo[b]pyrazino[l,2-d][l,4]oxazinyl, 2,3,4,4a,5,6-hexahydro-lH-benzo[b]pyrazino[l,2-d][l,4]oxazepinyl, l,2,3,4,4a,5-hexahydro-7H-benzo[e]pyrazino[2,l-c][l,4]oxazepinyl, 2,3,4,4a-tetrahydro-lH-pyrazino[l,2-a]quinoxalin-5(6H)-onyl, l,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[l,2-d][l,4]diazepin-6(7H)-onyl, 2, 3, 4, 4a, 5,6-hexahydro-lH-pyrazino[l,2-a]quinoxalinyl, and l',2',5',6',8',8a'-hexahydro-3H-dispiro[isobenzofuran-l,7'-indolizine-3',4"-piperidinyl].

[0276] In some embodiments, Ring D3 is selected from 6, 6a, 7, 8, 9, 10-hexahydrobenzo [b]pyrido [ 1,2-d] [ 1,4] oxazinyl, 2,3 -dihydrospiro [indene- 1,4'-piperidinyl], l,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[l,2-d][l,4]oxazinyl, and 2,3-dihydrospiro[indene-l,3'-pyrrolidinyl].

[0277] In some embodiments, Ring D3 is selected from 6, 6a, 7, 8, 9, 10-hexahydrobenzo[b]pyrido[l,2-d] [l,4]oxazinyl and 2,3-dihydrospiro[indene-l,4'-piperidinyl].

[0278] In some embodiments, LDis a bond.

[0279] In some embodiments, Ring C4 is 4-14 membered heterocycloalkyl.

[0280] In some embodiments, Ring C4 is 4-7 membered heterocycloalkyl.

[0281] In some embodiments, Ring C4 is 1,2,3,6-tetrahydropyridinyl.54057-0036W01 / SNV0027-W01 PATENT

[0282] In some embodiments, Ring

[0283]

[0284] is 4-14 membered heterocycloalkyl.

[0285] In some embodiments, Ring

[0286]

[0287] is 10-14 membered heterocycloalkyl.

[0288] In some embodiments, Ring

[0289]

[0290] is spiro [indene- 1,4'-piperidinyl], spiro[indoline-2,3'-pyrrolidin]-2'-onyl, and r,5',6',7'-tetrahydrospiro[piperidine-4,4'-pyrrolo[2,3-c]pyridine].

[0291] In some embodiments, Ring C5 is 4-14 membered heterocycloalkyl.

[0292] In some embodiments, Ring C5 is 4-7 membered heterocycloalkyl.

[0293] In some embodiments, Ring C5 is 1,2,3,6-tetrahydropyridinyl.

[0294] In some embodiments, X2is CH.

[0295] In some embodiments, X3is C.

[0296] In some embodiments, X4is CH.

[0297] In some embodiments, Y1is NH.

[0298] In some embodiments, Y2is C(RB).

[0299] In some embodiments, Z1is C.

[0300] In some embodiments, Z1is N.

[0301] In some embodiments,

[0302]

[0303] selected from l',3'-dihydrospiro[piperidine-4,5'-pyrano[3,4,5-cd]indolyl], 7H-pyrrolo[3,2,l-de]phenanthridinyl, 6,6a,7,8,9,10-hexahydro-4H-pyrazino[l,2-a]pyrrolo[4,3,2-de]quinolinyl, 7,8-dihydrobenzo[4,5]azepino[3,2,l-7h]indolyl, and 4,6-dihydronaphtho[3,2,l-cd]indolyl.

[0304]

[0305] dihydrospiro[piperidine-4,5'-pyrano[3,4,5-cd]indolyl], 7H-pyrrolo[3,2,l-de]phenanthridinyl, 6,6a,7,8,9,10-hexahydro-4H-pyrazino[l,2-a]pyrrolo[4,3,2-de]quinolinyl, and 7,8-dihydrobenzo[4,5]azepino[3,2,l-7h]indole.54057-0036W01 / SNV0027-W01 PATENT

[0306] In some embodiments,

[0307]

[0308] selected from 1', 3'-dihydrospiro[piperidine-4,5'-pyrano[3,4,5-cd]indolyl], 7H-pyrrolo[3,2,l-de]phenanthridinyl, and 6,6a,7,8,9,10-hexahydro-4H-pyrazino[l,2-a]pyrrolo[4,3,2-de]quinolinyl.

[0309] In some embodiments, Ring C6 is 4-14 membered heterocycloalkyl.

[0310] In some embodiments, Ring C6 is 4-7 membered heterocycloalkyl.

[0311] In some embodiments, Ring C6 is 1,2,3,6-tetrahydropyridinyl.

[0312] In some embodiments, X5is CH.

[0313] In some embodiments, X6is C.

[0314] In some embodiments, X7is C.

[0315] In some embodiments, X8is CH.

[0316] In some embodiments, Y3is NH.

[0317] In some embodiments, Z2is C.

[0318] In some embodiments, Z3is C.

[0319] In some embodiments,

[0320]

[0321] -tetrahydro-lH-pyrido[3,4-b]indol-l-onyl,

[0322] 3.4.5.10-tetrahydroazepino[3,4-b]indol-l(2H)-onyl,

[0323] 2,3,4,5,6, 11 -hexahydro- IH-azocino [3,4-b]indol- 1 -onyl,

[0324] 4',9'-dihydrospiro[cyclopropane-l,3'-pyrido[3,4-b]indol]-r(2'H)-onyl,

[0325] 2.3.5.10-tetrahydro- IH-spiro [azepino [3,4-b]indole-4, 1 -cyclopropan] - 1 -one.

[0326] In some embodiments,

[0327]

[0328] -tetrahydro-lH-pyrido[3,4-b]indol-l-onyl.

[0329] In some embodiments, Ring B7 is 14-20 membered heterocycloalkyl.

[0330] In some embodiments, Ring B7 is 14-18 membered heterocycloalkyl.

[0331] In some embodiments, Ring B7 is selected from 3, 5, 5a, 6, 7, 8, 9,9a-octahydropyrido[3',4':4,5]pyrano[3,2-g]indolyl, spiro[indoline-3,3'-piperidin]-2-onyl, 3,7-54057-0036W01 / SNV0027-W01 PATENT

[0332] dihydroisochromeno[4,3-e]indolyl, 6,1 l-dihydro-5H-benzo[b]pyrido[3,2-f]azepinyl, and l,2,3,4,5,10-hexahydropyrido[3',4':4,5]pyrano[2,3-f]indolyl.

[0333] In some embodiments, Ring B7 is selected from 3, 5, 5a, 6, 7, 8, 9, 9a-octahydropyrido[3',4':4,5]pyrano[3,2-g]indolyl, spiro[indoline-3,3'-piperidin]-2-onyl, 3,7-dihydroisochromeno[4,3-e]indolyl, and 6,1 l-dihydro-5H-benzo[b]pyrido[3,2-f]azepinyl.

[0334] In some embodiments, Ring C8 is 4-14 membered heterocycloalkyl.

[0335] In some embodiments, Ring C8 is 4-7 membered heterocycloalkyl.

[0336] In some embodiments, Ring C8 is 1,2,3,6-tetrahydropyridinyl.

[0337] In some embodiments, Ring B8 is 5-14 membered heteroaryl.

[0338] In some embodiments, Ring B8 is 8-10 membered heteroaryl.

[0339] In some embodiments, Ring B8 is indolyl.

[0340] In some embodiments, Ring D8 is Ce-io aryl.

[0341] In some embodiments, Ring D8 is phenyl.

[0342] In some embodiments, Ring CIO is 4-14 membered heterocycloalkyl.

[0343] In some embodiments, Ring CIO is 4-7 membered heterocycloalkyl.

[0344] In some embodiments, Ring CIO is 1,2,3,6-tetrahydropyridinyl.

[0345] In some embodiments, Ring BIO is 5-14 membered heteroaryl.

[0346] In some embodiments, Ring BIO is 8-10 membered heteroaryl.

[0347] In some embodiments, Ring BIO is indolyl.

[0348] In some embodiments, Ring F 10 is 4-14 membered heterocycloalkyl.

[0349] In some embodiments, Ring F10 is 4-7 membered heterocycloalkyl.

[0350] In some embodiments, Ring F10 is piperidinyl.

[0351] In some embodiments, LFis C(O).

[0352] In some embodiments, R10Aand R10Bare each H.

[0353] In some embodiments, Ring C12 is 4-14 membered heterocycloalkyl.

[0354] In some embodiments, Ring C12 is 4-7 membered heterocycloalkyl.

[0355] In some embodiments, Ring C12 is 1,2,3,6-tetrahydropyridinyl.

[0356] In some embodiments, X9is C.

[0357] In some embodiments, X10is CH.

[0358] In some embodiments, X11is C.

[0359] In some embodiments, X12is CH.

[0360] In some embodiments, Y4is NH.

[0361] In some embodiments, Y5is C=O.

[0362] In some embodiments, R12Aand R12Bare each independently selected from H and 5-6 membered heteroaryl, wherein the 5-6 membered heteroaryl is optionally substituted with 1 or 2 R° substituents independently selected from Ci-6 alkyl.54057-0036W01 / SNV0027-W01 PATENT

[0363] In some embodiments, R12Aand R12Bare each independently selected from H and pyrrolyl, wherein the pyrrolyl is optionally substituted with 1 or 2 R° substituents independently selected from C1-3 alkyl.

[0364] In some embodiments, R12Aand R12Bare each independently selected from H and dimethylpyrrolyl.

[0365] In some embodiments, STAT6L is a STAT6 binding moiety selected from

[0366]

[0367] 54057-0036W01 / SNV0027-W01 PATENT

[0368]

[0369] 54057-0036W01 / SNV0027-W01 PATENT

[0370]

[0371] 54057-0036W01 / SNV0027-W01 PATENT

[0372]

[0373] 54057-0036W01 / SNV0027-W01 PATENT

[0374]

[0375] 54057-0036W01 / SNV0027-W01 PATENT

[0376]

[0377] 54057-0036W01 / SNV0027-W01 PATENT

[0378]

[0379] 54057-0036W01 / SNV0027-W01 PATENT

[0380]

[0381] 54057-0036W01 / SNV0027-W01 PATENT

[0382]

[0383] wherein> / vvvvvv' refers to the bond between STAT6L and L.

[0384] In some embodiments, STAT6L is a STAT6 binding moiety selected from

[0385]

[0386] 54057-0036W01 / SNV0027-W01 PATENT

[0387]

[0388] 54057-0036W01 / SNV0027-W01 PATENT

[0389]

[0390] 54057-0036W01 / SNV0027-W01 PATENT

[0391]

[0392] 54057-0036W01 / SNV0027-W01 PATENT

[0393]

[0394] 54057-0036W01 / SNV0027-W01 PATENT

[0395]

[0396] 54057-0036W01 / SNV0027-W01 PATENT

[0397]

[0398] 54057-0036W01 / SNV0027-W01 PATENT

[0399]

[0400] In some embodiments, STAT6L is a STAT6 binding moiety selected from

[0401]

[0402] 54057-0036W01 / SNV0027-W01 PATENT

[0403]

[0404] 54057-0036W01 / SNV0027-W01 PATENT

[0405]

[0406] 54057-0036W01 / SNV0027-W01 PATENT

[0407]

[0408] 54057-0036W01 / SNV0027-W01 PATENT

[0409]

[0410] 54057-0036W01 / SNV0027-W01 PATENT

[0411]

[0412] 54057-0036W01 / SNV0027-W01 PATENT

[0413]

[0414] wherein * refers to the bond between STAT6L and L.

[0415] In some embodiments, STAT6L is a STAT6 binding moiety selected from

[0416]

[0417] 54057-0036W01 / SNV0027-W01 PATENT

[0418]

[0419] 54057-0036W01 / SNV0027-W01 PATENT

[0420]

[0421] 54057-0036W01 / SNV0027-W01 PATENT

[0422]

[0423] 54057-0036W01 / SNV0027-W01 PATENT

[0424] wherein ■ / www' refers to the bond between STAT6L and L.

[0425] In some embodiments, LBis C O alkylene.

[0426] In some embodiments, LBis Ci-6 alkylene.

[0427] In some embodiments, LBis C1-3 alkylene.

[0428] In some embodiments, LBis -CH2-.

[0429] In some embodiments,

[0430]

[0431] In some embodiments, Ring C2 is 4-14 membered heterocycloalkyl or 5-10 membered heteroaryl.

[0432] In some embodiments, Ring C2 is 4-14 membered heterocycloalkyl.

[0433] In some embodiments, Ring C2 is 4-7 membered heterocycloalkyl.

[0434] In some embodiments, Ring C2 is 5-10 membered heteroaryl.

[0435] In some embodiments, Ring C2 is 5-6 membered heteroaryl.

[0436] In some embodiments, Ring C2 is pyrrolidinyl or pyridinyl.

[0437] In some embodiments, Ring C2 is pyrrolidinyl.

[0438] In some embodiments, Ring C2 is pyridinyl.

[0439] / C7 J— Lc— Rz

[0440] In some embodiments, RZ7is

[0441] In some embodiments, Ring C7 is 4-14 membered heterocycloalkyl.

[0442] In some embodiments, Ring C7 is 4-7 membered heterocycloalkyl.

[0443] In some embodiments, Ring C7 is 1,2,3,6-tetrahydropyridinyl.

[0444] In some embodiments, RZ7is -Lc-Rz.

[0445] In some embodiments, Lcis selected from a bond and C O alkylene, wherein 1 or 2 methylene groups are each independently and optionally replaced by -C(O)-.

[0446] In some embodiments, Lcis selected from a bond and C1-6 alkylene, wherein 1 or 2 methylene groups are each independently and optionally replaced by -C(O)-.

[0447] In some embodiments, Lcis selected from a bond and C1-3 alkylene, wherein 1 or 2 methylene groups are each independently and optionally replaced by -C(O)-.

[0448] In some embodiments, Lcis selected from a bond, -CH2, -CH2CH2-, -C(O)CH2- and -CH2CH2C(O)-.

[0449] In some embodiments, Lcis selected from a bond, -CH2, -CH2CH2-, and -CH2CH2C(O)-.

[0450] In some embodiments, Rzis selected from H and

[0451]

[0452] 54057-0036W01 / SNV0027-W01 PATENT

[0453] In some embodiments, Rzis H.

[0454] In some embodiments,

[0455]

[0456] In some embodiments, Ring Z is selected from 4-14 membered heterocycloalkyl and 5-10 membered heteroaryl.

[0457] In some embodiments, Ring Z is selected from 8-14 membered heterocycloalkyl and 5-6 membered heteroaryl.

[0458] In some embodiments, Ring Z is selected from l,5,8,8a-tetrahydroimidazo[l,5-a]pyridin-3(2H)-onyl, 2,7-diazaspiro[4.5]decan-l-onyl, pyrazolyl, and triazolyl.

[0459] In some embodiments, Ring Z is selected from

[0460]

[0461]

[0462] In some embodiments, each Rzois independently selected from C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-ealkynyl, and C1-6 haloalkyl.

[0463] In some embodiments, each Rzois independently selected from C1-6 alkyl and C1-6 haloalkyl.

[0464] In some embodiments, each Rzois independently selected from C1-6 alkyl.

[0465] In some embodiments, each Rzois independently selected from C1-3 alkyl.

[0466] In some embodiments, Rzis selected from

[0467]

[0468]

[0469] In some embodiments, each RB, Rc, RD, RE, and RFis independently selected from H, halo, C1-6 alkyl, Ci- 6 alkylidenyl, C2-6 alkenyl, C2-ealkynyl, C1-6 haloalkyl, -C(O)R, -C(O)NR2, and -C(O)NRNR2.

[0470] In some embodiments, each RB, Rc, RD, RE, and RFis independently selected from H, halo, C1.6 alkyl, -C(O)R, -C(O)NR2, -C(O)NRNR2.54057-0036W01 / SNV0027-W01 PATENT

[0471] In some embodiments, each RB, Rc, RD, RE, and RFis independently selected from H, halo, Ci-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-ealkynyl, C1-6 haloalkyl, and -C(O)NR2.

[0472] In some embodiments, each RB, Rc, RD, RE, and RFis independently selected from halo, C1-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-ealkynyl, C1-6 haloalkyl, and -C(O)NR2.

[0473] In some embodiments, each RB, Rc, RD, RE, and RFis independently selected from H, C1-6 alkyl, and -C(O)NR2.

[0474] In some embodiments, each RB, Rc, RD, RE, and RFis independently selected from Ci-6 alkyl and -C(O)NR2.

[0475] In some embodiments, LBDis Ci-w alkylene, wherein 1-6 methylene groups of the Ci-10 alkylene are each independently and optionally replaced by -O- or -N(R)C(O)-.

[0476] In some embodiments, LBDis C3-7 alkylene, wherein 2-4 methylene groups of the C3-7 alkylene are each independently and optionally replaced by -O- or -N(R)C(O)-.

[0477] In some embodiments, each R is independently selected from H, C1-6 alkyl, 4-10 membered heterocycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-C1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, 4-10 membered heterocycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents.

[0478] In some embodiments, each R is independently selected from H, C1-3 alkyl, 4-7 membered heterocycloalkyl, C3-7 cycloalkyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, 4-7 membered heterocycloalkyl, C3-7 cycloalkyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl) -C 1.4 alkyl of R are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents.

[0479] In some embodiments, each R° is independently selected from H, halo, C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-ealkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, and -C(O)NRc0Rd0, wherein each C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-ealkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents.

[0480] In some embodiments, each R° is independently selected from H, halo, C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-ealkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, and -C(O)NRc0Rd0, wherein each C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-ealkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl is optionally substituted with 1, 2, 3, 4, 5, or 6 R0Asubstituents independently selected from OH and CN.54057-0036W01 / SNV0027-W01 PATENT

[0481] In some embodiments, each R° is independently selected from H, halo, Ci-6 alkyl, Ci-6 alkylidenyl, C2-6 alkenyl, C2-ealkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, and -C(O)NRc0Rd0, wherein each C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-ealkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl is optionally substituted with 1 or 2 R0Asubstituents independently selected from OH and CN.

[0482] In some embodiments, each R° is independently selected from H, C1-6 alkyl, C1-6 alkylidenyl, C3-10 cycloalkyl, and -C(O)NRc0Rd0, wherein each C1-6 alkyl is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents.

[0483] In some embodiments, each R° is independently selected from H, C1-6 alkyl, C1-6 alkylidenyl, C3-10 cycloalkyl, and -C(O)NRc0Rd0, wherein each C1-6 alkyl is optionally substituted with 1, 2, 3, 4, 5, or 6 R0Asubstituents independently selected from OH and CN.

[0484] In some embodiments, each R° is independently selected from H, C1-6 alkyl, C1-6 alkylidenyl, C3-10 cycloalkyl, and -C(O)NRc0Rd0, wherein each C1-6 alkyl is optionally substituted with 1 or 2 R0Asubstituents independently selected from OH and CN.

[0485] In some embodiments, each R° is independently selected from H, C1-6 alkyl, C1-6 alkylidenyl, C3-10 cycloalkyl, and -C(O)NRc0Rd0, wherein each C1-6 alkyl is optionally substituted with OH or CN.

[0486] In some embodiments, each R° is independently selected from H, C1-6 alkyl, C1-6 alkylidenyl, C3-7 cycloalkyl, and -C(O)NRc0Rd0, wherein each C1-6 alkyl is optionally substituted with OH or CN.

[0487] In some embodiments, each Ra0, Rc0, and Rd0is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl.

[0488] In some embodiments, each Ra0, Rc0, and Rd0is independently selected from H and C1-6 alkyl.

[0489] In some embodiments, each Ra0, Rc0, and Rd0is independently selected from H and C1.3 alkyl.

[0490] In some embodiments, each Rc0and Rd0is independently selected from H and C1-6 alkyl.

[0491] In some embodiments, each Rc0and Rd0is independently selected from H and C1-3 alkyl.

[0492] In some embodiments, each Rc0and Rd0is independently selected from H and methyl. In some embodiments, each R is independently selected from H and C1-6 alkyl.

[0493] In some embodiments, each R is independently selected from H and C1-3 alkyl.

[0494] In some embodiments, each R is independently selected from H and methyl.54057-0036W01 / SNV0027-W01 PATENT

[0495] In some embodiments, each RB, Rc, RD, RE, and RFis independently selected from H, halo, Ci-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-ealkynyl, C1-6 haloalkyl, -C(O)R, -C(O)NR2, and -C(O)NRNR2;

[0496] each R is independently selected from H, C1-6 alkyl, 4-10 membered heterocycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, 4-10 membered heterocycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0497] each R° is independently selected from H, C1-6 alkyl, Ci-ealkylidenyl, C3-10 cycloalkyl, and -C(O)NRc0Rd0, wherein each C1-6 alkyl is optionally substituted with OH or CN; and each Rc0and Rd0is independently selected from H and C1-6 alkyl.

[0498] In some embodiments, each RB, Rc, RD, RE, and RFis independently selected from H, halo, C1.6 alkyl, -C(O)R, -C(O)NR2, -C(O)NRNR2;

[0499] each R is independently selected from H, C1-3 alkyl, 4-7 membered heterocycloalkyl, C3-7 cycloalkyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, 4-7 membered heterocycloalkyl, C3-7 cycloalkyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0500] each R° is independently selected from H, C1-6 alkyl, Ci-ealkylidenyl, C3-7 cycloalkyl, and -C(O)NRc0Rd0, wherein each C1-6 alkyl is optionally substituted with OH or CN; and each Rc0and Rd0is independently selected from H and C1-6 alkyl.

[0501] In some embodiments, each RB, Rc, RD, RE, and RFis independently selected from H, halo, C1-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-ealkynyl, C1-6 haloalkyl, and -C(O)NR2; and each R is independently selected from H and C1-6 alkyl.

[0502] In some embodiments, each RB, Rc, RD, RE, and RFis independently selected from halo, C1-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-ealkynyl, C1-6 haloalkyl, and -C(O)NR2; and each R is independently selected from H and C1-6 alkyl.

[0503] In some embodiments, each RB, Rc, RD, RE, and RFis independently selected from H, C1-6 alkyl, and -C(O)NR2; and

[0504] each R is independently selected from H and C1-3 alkyl.

[0505] In some embodiments, each RB, Rc, RD, RE, and RFis independently selected from Ci- 6 alkyl and -C(O)NR2; and

[0506] each R is independently selected from H and C1-3 alkyl.54057-0036W01 / SNV0027-W01 PATENT

[0507] In some embodiments, each RB, Rc, RD, RE, and RFis independently selected from H,

[0508]

[0509] In some embodiments, each RB, Rc, RD, RE, and RFis independently selected from H, methyl, and -C(O)N(CH3)2.

[0510] In some embodiments, each RB, Rc, RD, RE, and RFis independently selected from methyl and -C(O)N(CH3)2.

[0511] In some embodiments, LBDis Ci-w alkylene, wherein 1-6 methylene groups of the Ci-10 alkylene are each independently and optionally replaced by -O- or -N(R)C(O)-; and each R is independently selected from H and Ci-6 alkyl.

[0512] In some embodiments, LBDis C3-7 alkylene, wherein 2-4 methylene groups of the C3-7 alkylene are each independently and optionally replaced by -O- or -N(R)C(O)-; and

[0513] each R is independently selected from H and C1-3 alkyl.

[0514] In some embodiments, LBDis -C(O)N(CH3)-CH2CH2-O-.

[0515] In some embodiments, L is a bond or C1-20 alkylene, wherein 1-10 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -Cy-, -NH-, -N(CH3)-, or -C(O)-.

[0516] In some embodiments, L is a bond or C1-20 alkylene, wherein 1-10 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -Cy- or -C(O)-.

[0517] In some embodiments, L is a bond or C1-20 alkylene, wherein 1-10 methylene groups of the Ci -20 alkylene are each independently and optionally replaced by -Cy-.

[0518] In some embodiments, L is a bond.

[0519] In some embodiments, L is C1-20 alkylene, wherein 1-10 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -Cy-.54057-0036W01 / SNV0027-W01 PATENT

[0520] In some embodiments, each Cy is independently selected from C3-10 cycloalkyl, Ce-io aryl and 4-20 membered heterocycloalkyl, wherein the C3-10 cycloalkyl, Ce-io aryl, and 4-20 membered heterocycloalkyl are each optionally substituted with 1 or 2 R° substituents.

[0521] In some embodiments, each Cy is independently selected from C3-10 cycloalkyl, Ce-io aryl and 4-20 membered heterocycloalkyl, wherein the C3-10 cycloalkyl, Ce-io aryl, and 4-20 membered heterocycloalkyl are each optionally substituted with 1 or 2 R° substituents independently selected from C1-6 alkoxy.

[0522] In some embodiments, each Cy is independently selected from C3-7 cycloalkyl, phenyl, and 4-20 membered heterocycloalkyl wherein the C3-7 cycloalkyl, phenyl, and 4-20 membered heterocycloalkyl are each optionally substituted with 1 or 2 R° substituents.

[0523] In some embodiments, each Cy is independently selected from C3-7 cycloalkyl, phenyl, and 4-20 membered heterocycloalkyl wherein the C3-7 cycloalkyl, phenyl, and 4-20 membered heterocycloalkyl are each optionally substituted with 1 or 2 R° substituents independently selected from C1-6 alkoxy.

[0524] In some embodiments, each Cy is independently selected from Ce-io aryl and 4-20 membered heterocycloalkyl, wherein the Ce-io aryl and 4-20 membered heterocycloalkyl are each optionally substituted with 1 or 2 R° substituents.

[0525] In some embodiments, each Cy is independently selected from phenyl and 4-7 membered heterocycloalkyl wherein the phenyl and 4-7 membered heterocycloalkyl are each optionally substituted with 1 or 2 R° substituents.

[0526] In some embodiments, each Cy is independently selected from cyclohexyl, phenyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, 3H-spiro [isobenzofuran- l,4'-piperidinyl], l,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[l,2-d][l,4]oxazinyl, 2,3-dihydrospiro[indene-l,4'-piperidinyl], and 2,8-diazaspiro[4.5]decanyl, wherein the cyclohexyl, phenyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, 3H-spiro[isobenzofuran-l,4'-piperidinyl], 1,2, 3, 4, 4a, 5-hexahydrobenzo [b]pyrazino [ 1,2-d] [ 1,4]oxazinyl, 2,3 -dihydrospiro [indene- 1,4'-piperidinyl], and 2,8-diazaspiro[4.5]decanyl are each optionally substituted with 1 or 2 R° substituents.

[0527] In some embodiments, each Cy is independently selected from cyclohexyl, phenyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, 3H-spiro [isobenzofuran- l,4'-piperidinyl], l,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[l,2-d][l,4]oxazinyl, 2,3-dihydrospiro[indene-l,4'-piperidinyl], and 2,8-diazaspiro[4.5]decanyl, wherein the cyclohexyl, phenyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, 3H-spiro[isobenzofuran-l,4'-piperidinyl], 1,2, 3, 4, 4a, 5-hexahydrobenzo [b]pyrazino [ 1,2-d] [ 1,4]oxazinyl, 2,3 -dihydrospiro [indene- 1,4'-piperidinyl], and 2,8-diazaspiro[4.5]decanyl are each optionally substituted with 1 or 2 R° substituents independently selected from halo and C1-6 alkoxy.54057-0036W01 / SNV0027-W01 PATENT

[0528] In some embodiments, each Cy is independently selected from cyclohexyl, phenyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, and 3H-spiro [isobenzofuran- 1,4'-piperidinyl], wherein the cyclohexyl, phenyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, and 3H-spiro [isobenzofuran- l,4'-piperidinyl] are each optionally substituted with 1 or 2 R° substituents.

[0529] In some embodiments, each Cy is independently selected from cyclohexyl, phenyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, and 3H-spiro [isobenzofuran- 1,4'-piperidinyl], wherein the cyclohexyl, phenyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, and 3H-spiro [isobenzofuran- l,4'-piperidinyl] are each optionally substituted with 1 or 2 R° substituents independently selected from Ci-6 alkoxy.

[0530] In some embodiments, each Cy is independently selected from phenyl, piperidinyl, and piperazinyl, wherein the phenyl, piperidinyl, and piperazinyl are each optionally substituted with 1 or 2 R° substituents independently selected from Ci-6 alkoxy.

[0531] In some embodiments, each Cy is independently selected from phenyl, piperidinyl, and piperazinyl, wherein the phenyl, piperidinyl, and piperazinyl are each optionally substituted with 1 or 2 R° substituents independently selected from Ci-6 alkoxy.

[0532] In some embodiments, L is a bond or CMO alkylene, wherein 1-5 methylene groups of the CMO alkylene are each independently and optionally replaced by -Cy-, -NH-, -NfCfE)-. or -C(O)-; and

[0533] each Cy is independently selected from cyclohexyl, phenyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, 3H-spiro[isobenzofuran-l,4'-piperidinyl], 1,2, 3, 4, 4a, 5-hexahydrobenzo [b]pyrazino [ 1,2-d] [ 1,4]oxazinyl, 2,3 -dihydrospiro [indene- 1,4'-piperidinyl], and 2,8-diazaspiro[4.5]decanyl, wherein the cyclohexyl, phenyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, 3H-spiro[isobenzofuran-l,4'-piperidinyl], 1,2, 3, 4, 4a, 5-hexahydrobenzo [b]pyrazino [ 1,2-d] [ 1,4]oxazinyl, 2,3 -dihydrospiro [indene- 1,4'-piperidinyl], and 2,8-diazaspiro[4.5]decanyl are each optionally substituted with 1 or 2 R° substituents independently selected from halo and Ci-6 alkoxy.

[0534] In some embodiments, L is a bond or C1-20 alkylene, wherein 1-10 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -Cy- or -C(O)-; and each Cy is independently selected from C3-10 cycloalkyl, Ce-io aryl, and 4-20 membered heterocycloalkyl, wherein the C3-10 cycloalkyl, Ce-io aryl, and 4-20 membered heterocycloalkyl are each optionally substituted with 1 or 2 R° substituents.

[0535] In some embodiments, L is a bond or CMO alkylene, wherein 1-5 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -Cy- or -C(O)-; and54057-0036W01 / SNV0027-W01 PATENT

[0536] each Cy is independently selected from C3-7 cycloalkyl, phenyl, and 4-20 membered heterocycloalkyl wherein the C3-7 cycloalkyl, phenyl, and 4-20 membered heterocycloalkyl are each optionally substituted with 1 or 2 R° substituents.

[0537] In some embodiments, L is a bond or C O alkylene, wherein 1-5 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -Cy- or -C(O)-; and each Cy is independently selected from cyclohexyl, phenyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, and 3H-spiro[isobenzofuran-l,4'-piperidinyl], wherein the cyclohexyl, phenyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, and 3H-spiro [isobenzofuran- l,4'-piperidinyl] are each optionally substituted with 1 or 2 R° substituents independently selected from C1-6 alkoxy.

[0538] In some embodiments, L is a bond or C1-20 alkylene, wherein 1-10 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -Cy-; and

[0539] each Cy is independently selected from Ce-io aryl and 4-20 membered heterocycloalkyl, wherein the Ce-io aryl and 4-20 membered heterocycloalkyl are each optionally substituted with 1 or 2 R° substituents.

[0540] In some embodiments, L is a bond or CMO alkylene, wherein 1-5 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -Cy-; and

[0541] each Cy is independently selected from phenyl and 4-7 membered heterocycloalkyl wherein the phenyl and 4-7 membered heterocycloalkyl are each optionally substituted with 1 or 2 R° substituents.

[0542] In some embodiments, L is a bond or CMO alkylene, wherein 1-5 methylene groups of the Ci-20 alkylene are each independently and optionally replaced by -Cy-; and

[0543] each Cy is independently selected from phenyl, piperidinyl, and piperazinyl, wherein the phenyl, piperidinyl, and piperazinyl are each optionally substituted with 1 or 2 R° substituents independently selected from Ci-6 alkoxy.

[0544] In some embodiments, L is selected from a bond, -CH2CH2-, -CH2CH2CH2-,

[0545]

[0546] 54057-0036W01 / SNV0027-W01 PATENT

[0547]

[0548] 54057-0036W01 / SNV0027-W01 PATENT

[0549]

[0550] 54057-0036W01 / SNV0027-W01 PATENT

[0551] In some embodiments, L is selected from a bond, -CH2CH2-, -CH2CH2CH2-,

[0552]

[0553] In some embodiments, E3L is H.

[0554] In some embodiments, E3L is an E3 ubiquitin ligase binding moiety of formula E3L-

[0555]

[0556] In some embodiments, Ring A is selected from C5-20 cycloalkyl, Ce-io aryl, 5-20 membered heterocycloalkyl, and 5-14 membered heteroaryl.

[0557] In some embodiments, Ring A is selected from Ce-io aryl, 5-20 membered heterocycloalkyl, and 5-14 membered heteroaryl.

[0558] In some embodiments, Ring A is selected from C5-14 cycloalkyl, Ce-io aryl, 5-14 membered heterocycloalkyl, and 5-14 membered heteroaryl;

[0559] In some embodiments, Ring A is selected from Ce-io aryl, 5-14 membered heterocycloalkyl, and 5-14 membered heteroaryl.54057-0036W01 / SNV0027-W01 PATENT

[0560] In some embodiments, Ring A is selected from phenyl, 8-10 membered heterocycloalkyl, and 8-10 membered heteroaryl.

[0561] In some embodiments, Ring A is selected from phenyl, indazolyl, and 1,3-dihydro-2H-benzo [d]imidazol-2-onyl.

[0562] In some embodiments, Ring A is selected from phenyl and l,3-dihydro-2H-benzo [d]imidazol-2-onyl.

[0563] In some embodiments, each RAis independently selected from halo, C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-ealkynyl, and C1-6 haloalkyl.

[0564] In some embodiments, each RAis independently selected from halo, C1-6 alkyl, and C1-6 haloalkyl.

[0565] In some embodiments, each RAis independently selected from halo, C1-3 alkyl, and C1-3 haloalkyl.

[0566] In some embodiments, each RAis independently selected from halo and C1-6 alkyl, In some embodiments, each RAis independently selected from halo and C1-3 alkyl, In some embodiments, each RAis independently selected from fluoro, chloro, and methyl.

[0567] In some embodiments, each RAis independently selected from fluoro and methyl.

[0568] In some embodiments, Ring A is selected from

[0569]

[0570]

[0571] In some

[0572]

[0573] , Ring A is selected from

[0574]

[0575]

[0576] 54057-0036W01 / SNV0027-W01 PATENT

[0577] In some embodiments, Ring A is selected from

[0578]

[0579]

[0580] In some embodiments, L1is a bond.

[0581] In some embodiments, X1is CR1.

[0582] In some embodiments, X1is CH.

[0583] In some embodiments, X1is N.

[0584] In some embodiments, W1is -CH2- or -C(O)-;

[0585] In some embodiments, W1is -C(O)-;

[0586] In some embodiments, W2is -CH2- or -C(O)-;

[0587] In some embodiments, W2is -C(O)-;

[0588] In some embodiments, W1and W2are each -C(O)-;

[0589] In some embodiments, W3is -CH2- or -C(O)-;

[0590] In some embodiments, W3is -CH2-;

[0591] In some embodiments, W4is -CH2- or -C(O)-;

[0592] In some embodiments, W4is -CH2-;

[0593] In some embodiments, W3and W4are each -CH2-;

[0594] In some embodiments:

[0595] W1and W2are each -C(O)-; and

[0596] W3and W4are each -CH2-.

[0597] In some embodiments,

[0598]

[0599] In some embodiments,

[0600]

[0601] In some embodiments,

[0602]

[0603] In some embodiments:54057-0036W01 / SNV0027-W01 PATENT

[0604] L1is a bond; and

[0605]

[0606] In some embodiments:

[0607] L1is a bond; and

[0608]

[0609] In some embodiments:

[0610] L1is a bond; and

[0611]

[0612] In some embodiments, m, n, o, p, q, r, and t are each independently 0, 1, 2, 3, or 4. In some embodiments, m, n, o, p, q, r, and t are each independently 0, 1, 2, or 3. In some embodiments, m is 0, 1, or 2.

[0613] In some embodiments, m is 0.

[0614] In some embodiments, m is 1.

[0615] In some embodiments, m is 2.

[0616] In some embodiments, n is 0, 1, or 2.

[0617] In some embodiments, n is 0.

[0618] In some embodiments, n is 1.

[0619] In some embodiments, n is 2.

[0620] In some embodiments, o is 0, 1, or 2.

[0621] In some embodiments, o is 0.

[0622] In some embodiments, o is 1.

[0623] In some embodiments, o is 2.

[0624] In some embodiments, p is 0, 1, or 2.

[0625] In some embodiments, p is 0.

[0626] In some embodiments, p is 1.

[0627] In some embodiments, p is 2.

[0628] In some embodiments, q is 0, 1, or 2.

[0629] In some embodiments, q is 0.

[0630] In some embodiments, q is 1.54057-0036W01 / SNV0027-W01 PATENT

[0631] In some embodiments, q is 2.

[0632] In some embodiments, r is 0, 1, or 2.

[0633] In some embodiments, r is 0.

[0634] In some embodiments, r is 1.

[0635] In some embodiments, r is 2.

[0636] In some embodiments, t is 0, 1, or 2.

[0637] In some embodiments, t is 0.

[0638] In some embodiments, t is 1.

[0639] In some embodiments, t is 2.

[0640] In some embodiments:

[0641] E3L is an E3 ubiquitin ligase binding moiety of formula E3L-1:

[0642]

[0643] 54057-0036W01 / SNV0027-W01 PATENT

[0644]

[0645] STAT6L-12A

[0646] m, n, o, p, q, r, and t are each independently 0, 1, 2, 3, or 4;

[0647] each ~ is independently a single bond or double bond;

[0648] Ring A is selected from Ce-io aryl, 5-14 membered heterocycloalkyl, and 5-14 membered heteroaryl;

[0649] each RAis independently selected from halo, Ci-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-ealkynyl, and C1-6 haloalkyl;

[0650] LBis Ci-10 alkylene;

[0651]

[0652] Ring C2 is 4-7 membered heterocycloalkyl or 5-10 membered heteroaryl;

[0653]

[0654] Ring C7 is 4-7 membered heterocycloalkyl;

[0655] Lcis selected from a bond and C1-6 alkylene, wherein 1 or 2 methylene groups are each independently and optionally replaced by -C(O)-;54057-0036W01 / SNV0027-W01 PATENT

[0656]

[0657] each RZ0is independently selected from Ci-6 alkyl, Ci.6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;

[0658] each RB, Rc, RD, RE, and RFis independently selected from H, halo, C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, -C(O)R, -C(O)NR2, and -C(O)NRNR2;

[0659] each R is independently selected from H, C1-6 alkyl, 4-10 membered heterocycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, 4-10 membered heterocycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0660] LBDis Ci-10 alkylene, wherein 1-6 methylene groups of the C1-10 alkylene are each independently and optionally replaced by -O- or -N(R)C(O)-;

[0661] R10Aand R10Bare each H;

[0662] R12Aand R12Bare each independently selected from H and 5-6 membered heteroaryl, wherein the 5-6 membered heteroaryl is optionally substituted with 1 or 2 R° substituents L is a bond or C1-20 alkylene, wherein 1-10 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -Cy-, -NH-, -N(CH3)-, or -C(O)-;

[0663] each Cy is independently selected from C3-10 cycloalkyl, Ce-io aryl, and 4-20 membered heterocycloalkyl, wherein the C3-10 cycloalkyl, Ce-io aryl, 4-20 membered heterocycloalkyl are each optionally substituted with 1 or 2 R° substituents;

[0664] each R° is independently selected from H, halo, C1-6 alkyl, C1-6 alkylidenyl, C3-10 cycloalkyl, and -C(O)NRc0Rd0, wherein each C1-6 alkyl is optionally substituted with OH or CN; and

[0665] each Ra0, Rc0, and Rd0is independently selected from H and C1-6 alkyl.

[0666] In some embodiments:54057-0036W01 / SNV0027-W01 PATENT

[0667]

[0668] STAT6L-12A

[0669] m, n, o, p, q, r, and t are each independently 0, 1, 2, 3, or 4;

[0670] each ~ is independently a single bond or double bond;54057-0036W01 / SNV0027-W01 PATENT

[0671] Ring A is selected from Ce-io aryl, 5-14 membered heterocycloalkyl, and 5-14 membered heteroaryl;

[0672] each RAis independently selected from halo, Ci-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-ealkynyl, and C1-6 haloalkyl;

[0673] LBis Ci-10 alkylene;

[0674]

[0675] Ring C2 is 4-7 membered heterocycloalkyl;

[0676]

[0677] Ring C7 is 4-7 membered heterocycloalkyl;

[0678] Lcis selected from a bond and C1-6 alkylene, wherein 1 or 2 methylene groups are each independently and optionally replaced by -C(O)-;

[0679] Rzis selected from

[0680]

[0681] Ring Z is selected from 4-14 membered heterocycloalkyl and 5-10 membered heteroaryl;

[0682]

[0683] each Rzois independently selected from C1-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;

[0684] each RB, Rc, RD, RE, and RFis independently selected from halo, C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, and -C(O)NR2;

[0685] each R is independently selected from H and C1-6 alkyl;

[0686] LBDis Ci-10 alkylene, wherein 1-6 methylene groups of the C1-10 alkylene are each independently and optionally replaced by -O- or -N(R)C(O)-;

[0687] R10Aand R10Bare each H;

[0688] R12Aand R12Bare each independently selected from H and 5-6 membered heteroaryl, wherein the 5-6 membered heteroaryl is optionally substituted with 1 or 2 R° substituents L is a bond or C1-20 alkylene, wherein 1-10 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -Cy-; and54057-0036W01 / SNV0027-W01 PATENT

[0689] each Cy is independently selected from Ce-io aryl and 4-20 membered heterocycloalkyl, wherein the Ce-io aryl and 4-20 membered heterocycloalkyl are each optionally substituted with 1 or 2 R° substituents; and

[0690] each R° is independently selected from Ci-6 alkyl and Ci-6 alkoxy.

[0691] In some embodiments:

[0692] E3L is H or an E3 ubiquitin ligase binding moiety of formula E3L-1:

[0693]

[0694] STAT6L is a STAT6 binding moiety selected from

[0695]

[0696]

[0697] 54057-0036W01 / SNV0027-W01 PATENT

[0698]

[0699] 54057-0036W01 / SNV0027-W01 PATENT

[0700]

[0701] 54057-0036W01 / SNV0027-W01 PATENT

[0702]

[0703] 54057-0036W01 / SNV0027-W01 PATENT

[0704]

[0705] 54057-0036W01 / SNV0027-W01 PATENT

[0706]

[0707] 54057-0036W01 / SNV0027-W01 PATENT

[0708]

[0709] 54057-0036W01 / SNV0027-W01 PATENT

[0710]

[0711] 54057-0036W01 / SNV0027-W01 PATENT

[0712]

[0713] 54057-0036W01 / SNV0027-W01 PATENT

[0714]

[0715] 54057-0036W01 / SNV0027-W01 PATENT

[0716] Ring A is selected from Ce-io aryl, 5-14 membered heterocycloalkyl, and 5-14 membered heteroaryl;

[0717] each RAis independently selected from halo, C1-6 alkyl, Ci -6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;

[0718] LBis CMO alkylene;

[0719]

[0720] Ring C2 is 4-7 membered heterocycloalkyl or 5-6 membered heteroaryl;

[0721]

[0722] Ring C7 is 4-14 membered heterocycloalkyl;

[0723] Lcis selected from a bond and C1-6 alkylene, wherein 1 or 2 methylene groups are each independently and optionally replaced by -C(O)-;

[0724] Rzis selected from

[0725]

[0726] Ring Z is selected from 4-14 membered heterocycloalkyl and 5-10 membered heteroaryl;

[0727]

[0728] each RZ0is independently selected from Ci-6 alkyl, Ci.6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;

[0729] each RB, Rc, RD, RE, and RFis independently selected from H, halo, C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, -C(O)R, -C(O)NR2, and -C(O)NRNR2;

[0730] each R is independently selected from H, C1-6 alkyl, 4-10 membered heterocycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, 4-10 membered heterocycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0731] LBDis Ci-10 alkylene, wherein 1-6 methylene groups of the C1-10 alkylene are each independently and optionally replaced by -O- or -N(R)C(O)-;

[0732] R10Aand R10Bare each H;54057-0036W01 / SNV0027-W01 PATENT

[0733] R12Aand R12Bare each independently selected from H and 5-6 membered heteroaryl, wherein the 5-6 membered heteroaryl is optionally substituted with 1 or 2 R° substituents L is a bond or C1-20 alkylene, wherein 1-10 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -Cy-, -NH-, -N(CH3)-. or -C(O)-; and each Cy is independently selected from C3-10 cycloalkyl, Ce-io aryl, and 4-20 membered heterocycloalkyl, wherein the C3-10 cycloalkyl, Ce-io aryl, and 4-20 membered heterocycloalkyl are each optionally substituted with 1 or 2 R° substituents; and

[0734] each R° is independently selected from H, halo, C1-6 alkyl, C1-6 alkylidenyl, C3-7 cycloalkyl, and -C(O)NRc0Rd0, wherein each C1-6 alkyl is optionally substituted with OH or CN;

[0735] and each Rc0and Rd0is independently selected from H and C1-6 alkyl.

[0736] In some embodiments:

[0737] E3L is H or an E3 ubiquitin ligase binding moiety of formula E3L-1:

[0738]

[0739] 54057-0036W01 / SNV0027-W01 PATENT

[0740]

[0741] 54057-0036W01 / SNV0027-W01 PATENT

[0742]

[0743] 54057-0036W01 / SNV0027-W01 PATENT

[0744]

[0745] 54057-0036W01 / SNV0027-W01 PATENT

[0746]

[0747] 54057-0036W01 / SNV0027-W01 PATENT

[0748]

[0749] 54057-0036W01 / SNV0027-W01 PATENT

[0750]

[0751] m and t are each independently 0, 1, 2, 3, or 4;

[0752] each ~ is independently a single bond or double bond;

[0753] Ring A is selected from Ce-io aryl, 5-14 membered heterocycloalkyl, and 5-14 membered heteroaryl;54057-0036W01 / SNV0027-W01 PATENT

[0754] each RAis independently selected from halo, Ci-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-ealkynyl, and C1-6 haloalkyl;

[0755] LBis Ci-10 alkylene;

[0756]

[0757] Ring C2 is 4-7 membered heterocycloalkyl;

[0758]

[0759] Ring C7 is 4-7 membered heterocycloalkyl;

[0760] Lcis selected from a bond and C1-6 alkylene, wherein 1 or 2 methylene groups are each independently and optionally replaced by -C(O)-;

[0761] Rzis selected from

[0762]

[0763] Ring Z is selected from 4-14 membered heterocycloalkyl and 5-10 membered heteroaryl;

[0764]

[0765] each Rzois independently selected from C1-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;

[0766] each RB, Rc, RD, RE, and RFis independently selected from H, halo, C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, -C(O)R, -C(O)NR2, and -C(O)NRNR2;

[0767] each R is independently selected from H, C1-6 alkyl, 4-10 membered heterocycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, 4-10 membered heterocycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;

[0768] LBDis Ci-10 alkylene, wherein 1-6 methylene groups of the C1-10 alkylene are each independently and optionally replaced by -O- or -N(R)C(O)-;

[0769] R10Aand R10Bare each H;

[0770] R12Aand R12Bare each independently selected from H and 5-6 membered heteroaryl, wherein the 5-6 membered heteroaryl is optionally substituted with 1 or 2 R° substituents54057-0036W01 / SNV0027-W01 PATENT

[0771] L is a bond or C1-20 alkylene, wherein 1-10 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -Cy- or -C(O)-; and

[0772] each Cy is independently selected from C3-10 cycloalkyl, Ce-io aryl, and 4-20 membered heterocycloalkyl, wherein the C3-10 cycloalkyl, Ce-io aryl, and 4-20 membered heterocycloalkyl are each optionally substituted with 1 or 2 R° substituents; and

[0773] each R° is independently selected from H, C1-6 alkyl, Ci-ealkylidenyl, C3-7 cycloalkyl, and -C(O)NRc0Rd0, wherein each C1-6 alkyl is optionally substituted with OH or CN;

[0774] and each Rc0and Rd0is independently selected from H and C1-6 alkyl.

[0775] In some embodiments:

[0776] STAT6L is a STAT6 binding moiety selected from

[0777]

[0778]

[0779] 54057-0036W01 / SNV0027-W01 PATENT

[0780]

[0781] 54057-0036W01 / SNV0027-W01 PATENT

[0782]

[0783] m and t are each independently 0, 1, 2, 3, or 4;

[0784] each ~ is independently a single bond or double bond;

[0785] Ring A is selected from Ce-io aryl, 5-14 membered heterocycloalkyl, and 5-14 membered heteroaryl;

[0786] each RAis independently selected from halo, Ci-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-ealkynyl, and C1-6 haloalkyl;

[0787] LBis Ci-10 alkylene;

[0788]

[0789] Ring C2 is 4-7 membered heterocycloalkyl;

[0790]

[0791] Ring C7 is 4-7 membered heterocycloalkyl;

[0792] Lcis selected from a bond and C1-6 alkylene, wherein 1 or 2 methylene groups are each independently and optionally replaced by -C(O)-;

[0793] Rzis selected from

[0794]

[0795] Ring Z is selected from 4-14 membered heterocycloalkyl and 5-10 membered heteroaryl;54057-0036W01 / SNV0027-W01 PATENT

[0796] Ring Z is selected from

[0797]

[0798] each RZ0is independently selected from Ci-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;

[0799] each RB, Rc, RD, RE, and RFis independently selected from H, halo, C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, and -C(0)NR2;

[0800] each R is independently selected from H and C1-6 alkyl;

[0801] LBDis Ci-10 alkylene, wherein 1-6 methylene groups of the C1-10 alkylene are each independently and optionally replaced by -O- or -N(R)C(O)-;

[0802] R10Aand R10Bare each H;

[0803] R12Aand R12Bare each independently selected from H and 5-6 membered heteroaryl, wherein the 5-6 membered heteroaryl is optionally substituted with 1 or 2 R° substituents L is a bond or C1-20 alkylene, wherein 1-10 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -Cy-; and

[0804] each Cy is independently selected from Ce-io aryl and 4-20 membered heterocycloalkyl, wherein the Ce-io aryl and 4-20 membered heterocycloalkyl are each optionally substituted with 1 or 2 R° substituents; and

[0805] each R° is independently selected from C1-6 alkyl and C1-6 alkoxy.

[0806] In some embodiments, the compound provided herein is selected from:

[0807] 4-(4-( 1 -( 1 -(2,6-dioxopiperidin-3 -yl)-3 -methyl -2 -oxo-2, 3 -dihydro- 1H-benzo[d]imidazol-4-yl)piperidin-4-yl)-2-methoxyphenyl)-N, N-dimethyl-6-(2-methyl-3-oxo-1,2, 3, 5, 8, 8a-hexahydroimidazo[l,5-a]pyridin-6-yl)-lH-indole-2 -carboxamide;

[0808] 6-(3-(2-(lH-l,2,3-triazol-l-yl)ethyl)-5,8-dihydro-[l,2,4]triazolo[4,3-a]pyridin-6-yl)-4-(4-(4-(3-(l-(2, 6-dioxopiperidin-3-yl)-3 -methyl -2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-5-yl)propyl)piperazin- 1 -yl)phenyl)-N, N-dimethyl- lH-indole-2 -carboxamide;

[0809] 4-(4-(4-(2-( 1 -(2,6-dioxopiperidin-3 -yl)-3 -methyl -2 -oxo-2, 3 -dihydro- 1H-benzo[d]imidazol-4-yl)ethyl)piperazin- 1 -yl)-2-methoxyphenyl)-N, N-dimethyl-6-(2-methyl- 1 -oxo-2, 7 -diazaspiro [4.5] decan-7 -yl) - 1 H-indole -2 -carboxamide;

[0810] 6-(( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)pyrrolidin-2-yl)methyl)-4-(4-(4-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol-5 -yl)propyl)piperazin- 1 -yl)phenyl)-N, N-dimethyl- lH-indole-2 -carboxamide;

[0811] 6-( 1 -(3 -( IH-pyrazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -(2-( 1 -(2,6-dioxopiperidin-3-yl)-3 -methyl -2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-54057-0036W01 / SNV0027-W01 PATENT

[0812] l,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[l,2-d][l,4]oxazin-8-yl)-N, N-dimethyl-lH-indole-2-carboxamide;

[0813] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -(4 -(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)-2,3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-N, N-dimethyl- 1 H-indole -2 -carboxamide;

[0814] 5 -( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-7 -(4-(4-(2-( l-(2, 6-dioxopiperidin-3-yl)-3 -methyl -2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-5-yl)ethyl)piperazin- 1 -yl)-2-methoxyphenyl)-N, N, 1 '-trimethylspiro[indene- 1,4'-piperidine]-2-carboxamide;

[0815] 5 -( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)- 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)piperidin-4-yl)-N, N-dimethylspiro[indene-l,4'-piperidine]-2 -carboxamide;

[0816] 3-(4-(2-(4-(4-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)- 1 '-methyl -2'-oxospiro [indoline-2,3 '-pyrrolidin] -4-yl)-3 -methoxyphenyl)piperazin- 1 -yl)ethyl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0817] 1 '-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1 -(4-(4-(2-( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)piperazin-l-yl)-2-methoxyphenyl)-N, N-dimethyl-2-oxospiro[indoline-3,3'-piperidine]-6-carboxamide;

[0818] 6'-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)piperidin-3 -yl)- 1 -( 1 -(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)piperidin-4-yl)-N, N-dimethyl-r,5',6',7'-tetrahydrospiro[piperidine-4,4'-pyrrolo[2,3-c]pyridine]-2'-carboxamide;

[0819] 7'-( 1 -(3 -( IH-pyrazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)- 1 -( 1 -(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)piperidin-4-yl)-N, N-dimethyl-r,3'-dihydrospiro[piperidine-4,5'-pyrano[3,4,5-cd]indole]-2'-carboxamide;

[0820] 2-( 1 -(3 -( IH-pyrazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-9-(4-(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)piperidin-l-yl)-N, N-dimethyl-7H-pyrrolo[3,2,l-de]phenanthridine-5-carboxamide;

[0821] 2-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-8-(l-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)-N, N-dimethyl-6,6a,7,8,9,10-hexahydro-4H-pyrazino[l,2-a]pyrrolo[4,3,2-de]quinoline-5-carboxamide;

[0822] 3-(5-(3-(4-(4-(7-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-2 -methyl- 1 -oxo-2, 3,4,9-tetrahydro- IH-pyrido [3,4-b] indol-5 -yl)phenyl)piperazin- 1 -yl)propyl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;54057-0036W01 / SNV0027-W01 PATENT

[0823] 8-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 11 -(4-(4-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-5-yl)propyl)piperazin-l-yl)phenyl)-N, N-dimethyl-3,5,5a,6,7,8,9,9a-octahydropyrido[3',4':4,5]pyrano[3,2-g]indole-2-carboxamide;

[0824] 5 -( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-9-(4-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)piperazin-l-yl)-N, N-dimethyl-3,7-dihydroisochromeno[4,3-e]indole-2-carboxamide;

[0825] 3-(4-(2-(4-(4-(9-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)- 10-fluoro-6, 11 -dihydro-5H-benzo [b]pyrido[3,2-f] azepin-7 -y 1) -3 -methoxyphenyl)piperazin- 1 -yl)ethyl)-3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol- 1 -yl)piperidine -2, 6-dione;

[0826] 3-(4-(2-(4-(14-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-8-methyl-9-oxo-6,7,8,9-tetrahydro-10,12-epiminodibenzo[h,j][l]oxa[4]azacycloundecin-3-yl)piperazin-l-yl)ethyl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2,6-dione;

[0827] 3-(4-(2-(4-(4-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-2-(4-methylenepiperidine- 1 -carbonyl)- lH-indol-4-yl)-3-methoxyphenyl)piperazin- 1 -yl)ethyl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0828] 3-(5-(3-(4-(4-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-3-((3,5-dimethyl-lH-pyrrol-2-yl)methylene)-2-oxoindolin-4-yl)phenyl)piperazin-l-yl)propyl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0829] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-l,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[l,2-d][l,4]oxazin-8-yl)-N, N-dimethyl-lH-indole-2-carboxamide;

[0830] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( l'-(2-( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)ethyl)-2,3 -dihydrospiro[indene-l,4'-piperidin]-5-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;

[0831] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-l,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[l,2-d][l,4]oxazin-9-yl)-N, N-dimethyl-lH-indole-2-carboxamide;

[0832] 2-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-9-(4-(2-( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)ethyl)piperazin-l-yl)-N, N-dimethyl-7H-pyrrolo[3,2,l-de]phenanthridine-5-carboxamide;54057-0036W01 / SNV0027-W01 PATENT

[0833] 2-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-9-(4-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)piperazin-l-yl)-N, N-dimethyl-7H-pyrrolo[3,2,l-de]phenanthridine-5-carboxamide;

[0834] 2-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-8-(3-(l-(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)-N, N-dimethyl-6,6a,7,8,9,10-hexahydro-4H-pyrazino[l,2-a]pyrrolo[4,3,2-de]quinoline-5-carboxamide;

[0835] 2-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-8-(l-(3-(l-(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)piperidin-4-yl)-N, N-dimethyl-6,6a,7,8,9,10-hexahydro-4H-pyrazino[l,2-a]pyrrolo[4,3,2-de]quinoline-5-carboxamide;

[0836] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( l'-(2-( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)ethyl)-2,3-dihydrospiro[indene-l,3'-pyrrolidin]-5-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;

[0837] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)-2, 3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;

[0838] 3-(5-(3-(4-(4-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-r-methyl-2'-oxospiro[indoline-2,3'-pyrrolidin]-4-yl)phenyl)piperazin-l-yl)propyl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0839] ll-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7-(4-(2-(l-(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)ethyl)piperazin-l-yl)-N, N-dimethyl-4,5-dihydrobenzo[4,5]azepino[3,2,l-hi]indole-2-carboxamide;

[0840] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -( 1 -( 3 -(2,6-dioxopiperidin-3-yl)-l-methyl-lH-indazol-7-yl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;

[0841] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -(2 -( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;

[0842] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -(4 -(2,6-dioxopiperidin-3-yl)-2-fluorophenethyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro -N, N -dimethyl- 1 H-indole-2 -carboxamide;

[0843] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -( 1 -(4 -(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;54057-0036W01 / SNV0027-W01 PATENT

[0844] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -(2 -( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-lH-indazol-4-yl)ethyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;

[0845] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2-carboxamide;

[0846] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -(2 -( 3 -(2,6-dioxopiperidin-3 -yl)- 1 -methyl- lH-indazol-7 -yl)ethyl)-3H-spiro [isobenzofuran- 1,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;

[0847] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2-carboxamide;

[0848] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-lH-indazol-4-yl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;

[0849] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-( 1 -(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)- 1 -methyl-lH-indazol-6-yl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;

[0850] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)azetidin-3 -yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2-carboxamide;

[0851] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -( 1 -(4 -chloro-3-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)benzoyl)azetidin-3-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;

[0852] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -( 1 -(4 -chloro-3-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)benzoyl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;

[0853] 3-(5-(4-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7 -fluoro-2-(3 -methyleneazetidine- 1 -carbonyl)- lH-indol-4-yl)-3H-spiro[isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol- 1 -yl)piperidine -2, 6-dione;54057-0036W01 / SNV0027-W01 PATENT

[0854] 3-(4-(4-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7 -fluoro-2-(3 -methyleneazetidine- 1 -carbonyl)- lH-indol-4-yl)-3H-spiro[isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -fluorophenyl)piperidine-2, 6-dione;

[0855] l-(6-(4-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7 -fluoro-2-(3 -methyleneazetidine- 1 -carbonyl)- lH-indol-4-yl)-3H-spiro[isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1-yl)- 1 -methyl- lH-indazol-3-yl)dihydropyrimidine-2,4( 1H,3H)-dione;

[0856] 3-(6-(4-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7 -fluoro-2-(3 -methyleneazetidine- 1 -carbonyl)- lH-indol-4-yl)-3H-spiro[isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -yl)- 1 -methyl- lH-indazol-3 -yl)piperidine-2, 6-dione;

[0857] 3-(4-(4-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7 -fluoro-2-(3 -methyleneazetidine- 1 -carbonyl)- lH-indol-4-yl)-3H-spiro[isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol- 1 -yl)piperidine -2, 6-dione;

[0858] 3-(4-(3-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7 -fluoro-2-(3 -methyleneazetidine- 1 -carbonyl)- lH-indol-4-yl)-3H-spiro[isobenzofuran- 1,4'-piperidin] - 1 '-yl)azetidin- 1 -yl)-3-methyl-2-oxo-2,3-dihydro- lH-benzo[d]imidazol- 1 -yl)piperidine -2, 6-dione;

[0859] 3-(4-(2-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-2-(3-methyleneazetidine-l-carbonyl)-lH-indol-4-yl)-2,3-dihydrospiro[indene-l,4'-piperidin] - 1 '-yl)ethyl)-3-methyl-2-oxo-2,3-dihydro- lH-benzo[d]imidazol- 1 -yl)piperidine-2,6-dione;

[0860] 3-(4-(4-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-2-(3-methyleneazetidine-l-carbonyl)-lH-indol-4-yl)-2,3-dihydrospiro[indene-l,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol- 1 -yl)piperidine -2, 6-dione;

[0861] l-(6-(4-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7 -fluoro-2-(3 -methyleneazetidine- 1 -carbonyl)- lH-indol-4-yl)-3H-spiro[isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1-yl)- 1 -methyl- lH-indazol-3-yl)dihydropyrimidine-2,4( 1H,3H)-dione;

[0862] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -( 1 -(4 -(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)-6-fluoro-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;

[0863] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -(2 -( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;54057-0036W01 / SNV0027-W01 PATENT

[0864] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -(2 -( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-l-methyl-2-oxospiro[indoline-3,4'-piperidin]-6-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;

[0865] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -(2 -( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-l-methylspiro[indoline-3,4'-piperidin]-6-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;

[0866] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)-2-methyl-3-oxospiro[isoindoline-l,4'-piperidin]-5-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;

[0867] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( l'-(2-( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)ethyl)-3 -oxo-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;

[0868] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)-2-methylspiro[isoindoline-l,4'-piperidin]-5-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;

[0869] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)- 3.3-dimethyl-2-(methylimino)-2-oxido-2,3-dihydro-216-spiro[benzo[c]thiophene-l,4'-piperidin] -5 -yl) -N, N -dimethyl- 1 H-indole -2 -carboxamide;

[0870] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -(2 -( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-2H-spiro [benzofuran-3,4'-piperidin]-6-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;

[0871] 6-(5-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-5-azaspiro[3.5]non-7-en-7-yl)-4-(l'-(3-(l-(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)- 2.3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;

[0872] 6-((lS,5R)-8-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-8-azabicyclo[3.2.1]oct-2-en-2-yl)-4-(l'-(3-(l-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-5-yl)propyl)-2,3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-N, N-dimethyl-lH-indole-2-carboxamide;

[0873] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenethyl)-l,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[l,2-d][l,4]oxazin-8-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;

[0874] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-lH-indazol-4-yl)ethyl)-l,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[ 1,2-d] [ 1,4]oxazin-8-yl)-N, N-dimethyl- lH-indole-2-carboxamide;54057-0036W01 / SNV0027-W01 PATENT

[0875] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -( 1 -(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)-l,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[ 1,2-d] [ 1,4]oxazin-8-yl)-N, N-dimethyl- lH-indole-2-carboxamide;

[0876] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)piperidin-4-yl)-l,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[l,2-d][l,4]oxazin-8-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;

[0877] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -( 1 -(3 -(2,6-dioxopiperidin-3 -yl)- 1 -methyl- lH-indazol-6-yl)piperidin-4-yl)- 1,2,3,4,4a, 5 -hexahydrobenzo[b]pyrazino[ 1,2-d] [ 1,4]oxazin-8-yl)-N, N-dimethyl- lH-indole-2-carboxamide;

[0878] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( l'-(4-( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)cyclohexyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;

[0879] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-(( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)piperidin-4-yl)methyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2-carboxamide;

[0880] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)azetidine-3 -carbonyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2-carboxamide;

[0881] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)pyrrolidine- 3-carbonyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;

[0882] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)piperidine- 4-carbonyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;

[0883] 3-(5-(4-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7 -fluoro-2-(3-methyleneazetidine-l-carbonyl)-lH-indol-4-yl)-2,3-dihydrospiro[indene-l, d'piperidine] - 1 '-carbonyl)piperidin- 1 -yl)-3 -methyl -2 -oxo-2, 3 -dihydro- lH-benzo[d]imidazol- 1 -yl)piperidine -2, 6-dione;54057-0036W01 / SNV0027-W01 PATENT

[0884] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-2,3,4,4a,5,6-hexahydro-lH-benzo[b]pyrazino[l,2-d][l,4]oxazepin-9-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;

[0885] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-l,2,3,4,4a,5-hexahydro-7H-benzo[e]pyrazino[2,l-c][l,4]oxazepin-9-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;

[0886] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-6-methyl-5-oxo-2,3,4,4a,5,6-hexahydro-lH-pyrazino[l,2-a]quinoxalin-8-yl)-7-fluoro-N, N-dimethyl- 1 H-indole -2 -carboxamide;

[0887] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -(2-( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)ethyl)-7 -methyl-6-oxo-l,2,3,4,4a,5,6,7-octahydrobenzo[b]pyrazino[l,2-d][l,4]diazepin-9-yl)-7-fluoro-N, N -dimethyl- 1 H-indole -2 -carboxamide;

[0888] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-6-methyl-2,3,4,4a,5,6-hexahydro-lH-pyrazino[l,2-a]quinoxalin-8-yl)-7-fluoro-N, N-dimethyl-1 H-indole -2 -carboxamide;

[0889] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)-2,3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-7-fluoro-N, N', N'-trimethyl-lH-indole-2-carbohydrazide;

[0890] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( l'-(2-( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)ethyl)-2,3 -dihydrospiro[indene-l,4'-piperidin]-5-yl)-7-fluoro-N-methyl-N-((6-(methylcarbamoyl)pyridin-3-yl)methyl)-lH-indole-2 -carboxamide;

[0891] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)-2,3 -dihydrospiro [indene- 1,4'-piperidin] -5 -yl)-7 -fluoro-N-(2-( 1 -(hydroxymethyl)cyclopropyl)ethyl) -N -methyl- 1 H-indole -2 -carboxamide;

[0892] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)azetidine-3 -carbonyl)-2,3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-7-fluoro-N-methyl-N-(2-(6-(methylcarbamoyl)pyridin-3 -yl)ethyl) - 1 H-indole -2 -carboxamide;54057-0036W01 / SNV0027-W01 PATENT

[0893] 6-( 1 -(3-( 1H- 1,2,3-triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3-yl)-N-(2-( 1 -(cyanomethyl)piperidin-4-yl)ethyl)-4-(T-(3-(l-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro- IH-benzo [d]imidazol-5 -yl)propyl)-2, 3 -dihydrospiro [indene- 1,4'-piperidin] -5 -yl)-7 -fluoro -N -methyl - 1 H-indole-2 -carboxamide;

[0894] 6-( 1 -(3-( 1H- 1,2,3-triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3-yl)-N-(2-( 1 -(2-cyanoethyl)piperidin-4-yl)ethyl)-4-(r-(3-(l-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro- IH-benzo [d]imidazol-5 -yl)propyl)-2, 3 -dihydrospiro [indene- 1,4'-piperidin] -5 -yl)-7 -fluoro -N -methyl - 1 H-indole-2 -carboxamide;

[0895] 6-( 1 -(3-( 1H- 1,2,3-triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3-yl)-N-(2-( 1 -cyclopropylpiperidin-4-yl)ethyl)-4-(r-(3-(l-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro- IH-benzo [d]imidazol-5 -yl)propyl)-2, 3 -dihydrospiro [indene- 1,4'-piperidin] -5 -yl)-7 -fluoro -N -methyl - 1 H-indole-2 -carboxamide;

[0896] 3-(5-(3-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)- 7-fluoro-2-(3-(propan-2-ylidene)azetidine-l-carbonyl)-lH-indol-4-yl)-2,3-dihydrospiro| indene- 1,4'-piperidin]- 1 '-yl)propyl)-3-methyl-2-oxo-2,3-dihydro- 1H-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0897] 5 -( 1 -(3 -( 1H- 1,2,3-triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-7 -( 1 '-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)-2,3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-4-fluoro-N, N-dimethylbenzofuran-2-carboxamide;

[0898] 2-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-8-(4-(2-(l-(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)ethyl)piperazin-l-yl)-3-fluoro-N, N-dimethyl-4,6-dihydronaphtho[3,2,l-cd]indole-5-carboxamide;

[0899] 3-(4-(2-(5-(7-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)- 8-fluoro-2-methyl-l-oxo-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-5-yl)-2,3-dihydrospiro| indene- 1,4'-piperidin]- 1 '-yl)ethyl)-3-methyl-2-oxo-2,3-dihydro- 1H-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0900] 3-(4-(2-(4-(4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,2,3,4,5,10-hexahydroazepino[3,4-6]indol-6-yl)phenyl)piperazin- 1 -yl)ethyl)-3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol- 1 -yl)piperidine -2, 6-dione;

[0901] 3-(4-(2-(8-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)- 9-fluoro-2-methyl-l-oxo-l,2,3,4,5,10-hexahydroazepino[3,4-b]indol-6-yl)-l,2,4a,5-tetrahydrobenzo[b]pyrazino[l,2-d][l,4]oxazin-3(4H)-yl)ethyl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;54057-0036W01 / SNV0027-W01 PATENT

[0902] 3-(4-(2-(5-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,2,3,4,5,10-hexahydroazepino[3,4-b]indol-6-yl)-3H-spiro [isobenzofuran- 1, 4'-piperidin]-T-yl)ethyl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0903] 3-(4-(2-(4-(4-(9-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-10-fluoro-2-mcthyl-l-oxo-2.3.4.5.6.1 1 -hexahydro- 17 / -azocino| 3.4- / |indol-7-yl)phenyl)piperazin- 1 -yl)ethyl)-3 -methyl -2 -oxo-2, 3 -dihydro- 1 H-benzo [ d\ i m idazol - 1 -yl)piperidine -2, 6-dione;

[0904] 3-(4-(2-(4-(4-(7'-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-2'-methyl-r-oxo-r,2',4',9'-tetrahydrospiro[cyclopropane-l,3'-pyrido[3,4-6]indol]-5'-yl)phenyl)piperazin- 1 -yl)ethyl)-3 -methyl -2 -oxo-2, 3 -dihydro- 1 H-benzo [ d\ i m idazol - 1 -yl)piperidine -2, 6-dione;

[0905] 2-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)-7 -(4-(4-(2-( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -mcthyl-2-oxo-2.3-dihydro-l / / -bcnzo|d|imidazol-4-yl)cthyl)pipcrazin-l-yl)phcnyl)- '. '-dimethyl-l,2,3,4,5,10-hexahydropyrido[3',4':4,5]pyrano[2,3- / |indole-9-carboxamide;

[0906] 3-(5-(3-(5-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-cyclopropan] -6-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)propyl)-3 -methyl -2 -oxo-2, 3 -dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0907] 3-(5-(3-(5-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-cyclopropan] -6-yl)-3H-spiro [isobenzofuran- 1,4'-piperidine] - 1 '-carbonyl)azetidin- 1 -y 1) -3 -methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0908] 6-(6-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-6-azaspiro[3.5]non-8-en-8-yl)-4-(l'-(3-(l-(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2-carboxamide;

[0909] 6-(6-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-6-azaspiro[3.5]non-8-en-8-yl)-4-(l'-(l-(l-(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2-carboxamide;

[0910] 6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2-dihydroquinolin-3 -yl)-4-( 1 '-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol-5 -yl)propyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;54057-0036W01 / SNV0027-W01 PATENT

[0911] 6-(9-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)-9-azabicyclo [4.2.1 ]non-2-en-2-yl)-4-( 1 ' -(3 -(l-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-5-yl)propyl)-2, 3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;

[0912] 6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-2,4a,5,6,7,7a-hexahydro-lH-cyclopenta[b]pyridin-3-yl)-4-( l'-(3-( l-(2, 6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-5-yl)propyl)-2,3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-N, N-dimethyl- 1 H-indole -2 -carboxamide;

[0913] 6-(6-(3-( 1H- 1,2,3-triazol- 1 -yl)propanoyl)-6-azaspiro[3,5]nonan-8-yl)-4-( 1 '-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2-carboxamide;

[0914] 6-( 1 -(3 -( 1H- 1,2,3-triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 "-( 1 -(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)-r,2',5',6',8',8a'-hexahydro-3H-dispiro[isobenzofuran-l,7'-indolizine-3',4"-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;

[0915] 6-( 1 -(3-( 1H- 1,2,3-triazol- 1 -yl)propanoyl)- 1,2,5, 6-tetrahydropyridin-3-yl)-4-( 1 "-(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-r,2',5',6',8',8a'-hexahydro-3H-dispiro[isobenzofuran-l,7'-indolizine-3',4"-piperidin]-5-yl)-7-fluoro -N, N -dimethyl- 1 H-indole-2 -carboxamide;

[0916] 3-(5-(4-((4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-cyclopropan]-6-yl)-2,5-difluorobenzyl)amino)piperidin-l-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0917] 3-(5-(4-(4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3, T-cyclopropan]-6-yl)-2, 5-difluorobenzyl)piperazin-l-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0918] 3-(5-(4-(4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3, T-cyclopropan]-6-yl)-2, 5-difluorophenyl)-[l,4'-bipiperidin]-r-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0919] 3-(5-(4-(5-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-cyclopropan] -6-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl -2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;54057-0036W01 / SNV0027-W01 PATENT

[0920] 3-(6-(4-(5-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-cyclopropan] -6-yl)-3H-spiro[isobenzofuran- 1,4'-piperidin]- 1 '-yl)piperidin- 1 -yl)- 1 -methyl- 1H-indazol-3-yl)piperidine-2, 6-dione;

[0921] 3-(5-(4-(5-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fhioro-2 -methyl- 1 -oxo- 1 A5, 10-tetrahydro-2H-spiro [azepino [3,4-b] indole-3, T-cyclopropan] -6-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl -2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0922] 3-(5-(4-(4-(4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-cyclopropan] -6-yl)phenyl)piperazin- 1 -yl)piperidin- 1 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0923] 3-(5-(4-(4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-cyclopropan]-6-yl)-2, 3-difluorophenyl)-[l,4'-bipiperidin]-r-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0924] 3-(5-((4-(4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-cyclopropan] -6-yl)phenyl)piperazin- 1 -yl)methyl)-3 -methyl -2 -oxo-2, 3 -dihydro- 1H-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0925] 3-(5-(4-(8-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-cyclopropan] -6-yl)- 1,2,4a,5-tetrahydrobenzo[b]pyrazino[ 1,2-d] [ 1,4]oxazin-3(4H)-yl)piperidin-l-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2,6-dione;

[0926] 3-(5-(4-(5-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3, T-cyclopropan] -6-yl)-2, 3 -dihydrospiro [indene- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0927] 3-(5-(4-(4-(4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3, T-cyclopropan] -6-yl)-2,3 -difluorophenyl)piperazin- 1 -yl)piperidin- 1 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0928] 3-(5-((4-(4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3, T-54057-0036W01 / SNV0027-W01 PATENT

[0929] cyclopropan]-6-yl)-2,3-difluorophenyl)piperazin-l-yl)methyl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0930] 3-(5-(4-(5-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3, T-cyclopropan] -6-yl)-6-methoxy-3H-spiro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0931] 3-(5-(4-(4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3,l'-cyclopropan] -6-yl)piperazin- 1 -yl)piperidin- 1 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0932] 3-(5-(4-(8-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3, T-cyclopropan]-6-yl)-2,8-diazaspiro[4.5]decan-2-yl)piperidin-l-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0933] 5-(2-(dimethylcarbamoyl)-7-fluoro-6-(pyridin-3-yl)-lH-indol-4-yl)-N, N-dimethyl-3H-spiro [isobenzofuran- 1,4'-piperidine] - 1 '-carboxamide;

[0934] 6-(9-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-3-oxa-9-azabicyclo[3.3.1]non-6-en-6-yl)-4-( l'-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol-5 -yl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;

[0935] 6-(7-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-2-oxa-7-azaspiro[4.5]dec-9-en-9-yl)-4-(l'-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol-5 -yl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;

[0936] 6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-2,4a,5,6,7,7a-hexahydro-lH-cyclopenta[b]pyridin-3-yl)-4-( l'-(l-( l-(2, 6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-IH-benzo [d]imidazol-5 -yl)piperidin-4-yl)-2, 3 -dihydrospiro [indene- 1,4'-piperidin] -5 -yl)-7 -fluoro -N, N -dimethyl- 1 H-indole-2 -carboxamide;

[0937] 6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,4a,5,7,7a-hexahydrofuro[3,4-b]pyridin-3 -yl)-4-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol-5 -yl)piperidin-4-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] -5 -yl)-7 -fluoro-N, N -dimethyl- 1 H-indole -2 -carboxamide;

[0938] 3-(5-(4-(5-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4,r-cyclopropan] -6-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -yl)-4-fluoro-3 -methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;54057-0036W01 / SNV0027-W01 PATENT

[0939] 3-(5-(4-(8-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-cyclopropan] -6-yl)- 1,2,4a,5-tetrahydrobenzo[b]pyrazino[ 1,2-d] [ 1,4]oxazin-3(4H)-yl)piperidin- 1 -yl)-4-fluoro-3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol- 1 -yl)piperidine -2, 6-dione;

[0940] l-(5-(7-fluoro-4-(2-methoxyphenyl)-2-(3-methyleneazetidine-l-carbonyl)-lH-indol-6-yl)-3,6-dihydropyridin- 1 (2H)-yl)-3 -( 1H- 1,2,3 -triazol- 1 -yl)propan- 1 -one;

[0941] 1 -(5 -(4-( 1 '-acetyl-3H-spiro [isobenzofuran- 1,4'-piperidin] -5 -yl)-7 -fluoro-2-(3 -methyleneazetidine- 1 -carbonyl)- lH-indol-6-yl)-3,6-dihydropyridin- 1 (2H)-yl)-3 -( 1H- 1,2,3 -triazol - 1 -yl)propan- 1 -one;

[0942] 3 -(5 -(4-(8-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4,r-cyclopropan]-6-yl)-2 -fluoro-5-methoxyphenyl)-3 -methyl -2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine -2, 6-dione;

[0943] 3-(5-(4-((l-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3,r-cyclopropan]-6-yl)piperidin-4-yl)methyl)piperazin-l-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0944] 3-(5-(l-((l-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3,r-cyclopropan]-6-yl)piperidin-4-yl)methyl)piperidin-4-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0945] 3-(5-(4-(l-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3, T-cyclopropan] -6-yl)piperidin-4-yl)piperazin- 1 -yl)-3-methyl-2-oxo-2,3-dihydro- 1H-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0946] 3-(5-(4-(5-(7'-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-8'-fluoro-2'-methyl-r-oxo-r,2',4,4',5,9'-hexahydro-2H-spiro[furan-3,3'-pyrido[3,4-b]indol]-5 '-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0947] 3-(5-(4-(5-(7'-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-8'-fluoro-2'-methyl-r-oxo-r,2,2',3,4',5,6,9'-octahydrospiro[pyran-4,3'-pyrido[3,4-b]indol]-5'-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0948] 3-(5-(4-(5-(7'-(6-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-6-azaspiro[3.5]non-8-en-8-yl)-8'-fluoro-2'-methyl-r-oxo-r,2',4',9'-tetrahydrospiro[cyclopropane-l,3'-pyrido[3,4-b]indol]-5'-54057-0036W01 / SNV0027-W01 PATENT

[0949] yl)-2, 3 -dihydrospiro [indene- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0950] 3 -(5 -(4-(5 -(8-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)-5,5 -dimethyl- 1,2,5,6-tetrahydropyridin-3 -yl)-9-fluoro-2-methyl- 1 -oxo- 1,4,5, 10-tetrahydro-2H-spiro [azepino [3,4-b] indole-3, 1 '-cyclopropan] -6-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0951] 3-(5-(4-(5-(8-(6-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-6-azaspiro[3.5]non-8-en-8-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3, T-cyclopropan] -6-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl -2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0952] 3-(5-(4-(5-(8-(6-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-6-azaspiro[3.5]non-8-en-8-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3, T-cyclopropan] -6-yl)-2, 3 -dihydrospiro [indene- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;

[0953] 2-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)-7 -( l'-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)piperidin-4-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] -5 -yl)-N, N-dimethyl- 1,2,3,4,4a,5, 10, 11b-octahydropyrido[3',4':4,5]pyrano[2,3-f]indole-9-carboxamide;

[0954] 2-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)-7 -(2-methoxyphenyl)-N, N-dimethyl-l,2,3,4,4a,5,10,llb-octahydropyrido[3',4':4,5]pyrano[2,3-f]indole-9-carboxamide;

[0955] 2-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)-7 -( l'-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)piperidin-4-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] -5 -yl)- 11 -fluoro-N, N-dimethyl- 1, 2, 3, 4, 4a, 5, 10, 11b-octahydropyrido[3',4':4,5]pyrano[2,3-f]indole-9-carboxamide;

[0956] 2-(3 -( 1H- 1,2,3 -Triazol- 1 -yl)propanoyl)-7 -(4-(4-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-5-yl)piperidin-4-yl)piperazin-l-yl)phenyl)-N, N-dimethyl-l,2,3,4,4a,5,10,llb-octahydropyrido[3',4':4,5]pyrano[2,3-f]indole-9-carboxamide;

[0957] 2-Acetyl-7 -(4-( l'-( 1 -(2,6-dioxopiperidin-3 -yl)-3 -methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-5-yl)-[l,4'-bipiperidin]-4-yl)phenyl)-N, N-dimethyl-l,2,3,4,4a,5,10,llb-octahydropyrido[3',4':4,5]pyrano[2,3-f]indole-9-carboxamide;

[0958] 2-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)-8-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)piperidin-4-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] -5 -yl)-N, N-dimethyl- 1,2,3,4,6,7, 11, 12b-octahydropyrazino [2, 1 -a]pyrrolo [3,2-g] isoquinoline- 10-carboxamide;54057-0036W01 / SNV0027-W01 PATENT

[0959] 2-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)-7 -(2-methoxyphenyl)-N, N-dimethyl-l,2,3,4,4a,5,10,llb-octahydropyrido[3',4':4,5]pyrano[2,3-f]indole-9-carboxamide;

[0960] 2-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 11 -fluoro-7 -(2-methoxyphenyl)-N, N-dimethyl-l,2,3,4,4a,5,10,llb-octahydropyrido[3',4':4,5]pyrano[2,3-f]indole-9-carboxamide;

[0961] 2-(3-( 1H- 1,2,3-triazol- 1 -yl)propanoyl)-8-(2-methoxyphenyl)-N, N-dimethyl-l,2,3,4,6,7,ll,12b-octahydropyrazino[2,l-a]pyrrolo[3,2-g]isoquinoline-10-carboxamide;

[0962] 6-(6-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-6-azaspiro[3.5]non-8-en-8-yl)-7-fluoro-4-(2-methoxyphenyl) -N, N -dimethyl- 1 H-indole -2 -carboxamide;

[0963] 7'-(6-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-6-azaspiro[3.5]non-8-en-8-yl)-8'-fluoro-5'-(2-methoxyphenyl)-2'-methyl-4',9'-dihydrospiro[cyclopropane-l,3'-pyrido[3,4-b]indol]-l'(2'H)-one;

[0964] 2-(3 -( 1H- 1,2,3-triazol- 1 -yl)propanoyl)- 12-fluoro-8-(2-methoxyphenyl)-N, N-dimethyl-l,2,3,4,6,7,ll,12b-octahydropyrazino[2,l-a]pyrrolo[3,2-g]isoquinoline-10-carboxamide;

[0965] 2-(3 -( 1H- 1,2,3-triazol- 1 -yl)propanoyl)-8-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)piperidin-4-yl)-2,3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-12-fluoro-N, N-dimethyl-l,2,3,4,6,7,ll,12b-octahydropyrazino [2, 1 -a]pyrrolo [3,2-g] isoquinoline- 1 O-carboxamide;

[0966] 2-(3 -( 1H- 1,2,3-triazol- 1 -yl)propanoyl)-7 -(4-(4-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1 / / -benzo [d] imidazol-5 -yl)piperidin-4-yl)piperazin- 1 -yl)phenyl)-ll-fluoro- / V, / V-dimethyl-l,2,3,4,4a,5,10,llb-octahydropyrido[3',4':4,5]pyrano[2,3- |indole-9-carboxamide;

[0967] 2-(3 -( I / / - 1,2,3-triazol- 1 -yl)propanoyl)- 11 -fluoro-7 -(2-mcthoxy phen l )- '. -dimethyl-l,2,3,4,4a,5, 10, 1 lb-octahydropyrido[3',4':4,5]pyrano[2,3- / |indole-9-carboxamide;

[0968] 3 -(5 -(4-(5 -(9'-( 1 -(3 -( 12V- 1,2,3-triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-10'-fluoro-2'-methyl-r-oxo-r,2',4',5'-tetrahydrospiro[cyclopropane-l,3'-[l,4]diazepino[l,2-a] indol] -7'-y 1 ) -3 W-sp i ro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl-2-oxo-2.3-dihydro-l / / -bcnzo|d|imidazol-l-yl)pipcridinc-2.6-dione; and

[0969] 9'-(l-(3-(12V-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-10'-fluoro-7'-(2-methoxyphenyl)-2'-methyl-4',5'-dihydrospiro[cyclopropane-l,3'-[l,4]diazepino[l,2-a] indol] - 1 '(2 / )-one;

[0970] or a pharmaceutically acceptable salt thereof.

[0971] It is further appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, can also be provided in combination in a single embodiment. Conversely, various features of the invention which are, for brevity,54057-0036W01 / SNV0027-W01 PATENT

[0972] described in the context of a single embodiment, can also be provided separately or in any suitable subcombination.

[0973] At various places in the present specification, divalent linking substituents are described. It is specifically intended that each divalent linking substituent include both the forward and backward forms of the linking substituent. For example, -N(RL)C(O)- includes both -N(RL)C(O)- and -C(O)N(RL)- (e.g. -NHC(O)- includes both -NHC(O)- and -C(O)NH-). Where the structure clearly requires a linking group, the Markush variables listed for that group are understood to be linking groups.

[0974] The term “n-membered” where n is an integer typically describes the number of ring-forming atoms in a moiety where the number of ring-forming atoms is n. For example, piperidinyl is an example of a 6-membered heterocycloalkyl ring, pyrazolyl is an example of a 5 -membered heteroaryl ring, pyridyl is an example of a 6-membered heteroaryl ring, and 1,2,3,4-tetrahydro-naphthalene is an example of a 10-membered cycloalkyl group.

[0975] As used herein, the phrase “optionally substituted” means unsubstituted or substituted. The substituents are independently selected, and substitution may be at any chemically accessible position. As used herein, the term “substituted” means that a hydrogen atom is removed and replaced by a substituent. A single divalent substituent, e.g., oxo, can replace two hydrogen atoms. It is to be understood that substitution at a given atom is limited by valency.

[0976] As used herein, the phrase “each ‘variable’ is independently selected from” means substantially the same as wherein “at each occurrence ‘variable’ is selected from.” Throughout the definitions, the terms “Cn-m” and “Cm-n” indicates a range which includes the endpoints, wherein n and m are integers and indicate the number of carbons. Examples include C1-3, C1-4, C1-6, and the like.

[0977] As used herein, the term “Cn-malkyl”, employed alone or in combination with other terms, refers to a saturated hydrocarbon group that may be straight-chain or branched, having n to m carbons. Examples of alkyl moieties include, but are not limited to, chemical groups such as methyl (Me), ethyl (Et), n-propyl (n-Pr), isopropyl (iPr), n-butyl, tert-butyl, isobutyl, sec-butyl; higher homologs such as 2-methyl-1-butyl, n-pentyl, 3-pentyl, n-hexyl, 1,2,2-trimethylpropyl, and the like. In some embodiments, the alkyl group contains from 1 to 6 carbon atoms, from 1 to 4 carbon atoms, from 1 to 3 carbon atoms, from 2 to 6 carbon atoms, from 2 to 4 carbon atoms, from 2 to 3 carbon atoms, or 1 to 2 carbon atoms.

[0978] As used herein, “Cn-malkylidenyl” refers to an alkylidene group of formula R= and having n to m carbons, wherein R refers to an alkyl group as defined above. Example alkylidenyl groups include, but are not limited to, methylidenyl (H2C=), ethylidenyl (CH3CH=), n-propylidenyl (CH₃CH₂CH=), 2-propylidenyl ((CH3)2C=), and the like. For54057-0036W01 / SNV0027-W01 PATENT

[0979] example, in the compound below, the alkylidene group (methylidenyl) is enclosed by the box which is indicated by the arrow.

[0980]

[0981] The term “Cn-malkylidenyl” is understood to include deuterated analogs of alkylidene groups as defined herein, including but not limited to, groups such as dideuteromethylidenyl (D2C=), tetradeuteroethylidenyl (CDsCD=), and the like.

[0982] As used herein, “Cn-malkenyl” refers to an alkyl group having one or more double carbon-carbon bonds and having n to m carbons. Example alkenyl groups include, but are not limited to, ethenyl, n-propenyl, isopropenyl, n-butenyl, sec-butenyl, and the like. In some embodiments, the alkenyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms.

[0983] As used herein, “Cn-malkynyl” refers to an alkyl group having one or more triple carbon-carbon bonds and having n to m carbons. Example alkynyl groups include, but are not limited to, ethynyl, propyn-l-yl, propyn-2-yl, and the like. In some embodiments, the alkynyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms.

[0984] As used herein, the term “Cn-malkoxy”, employed alone or in combination with other terms, refers to a group of formula -O-alkyl, wherein the alkyl group has n to m carbons. Example alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy (e.g., n-propoxy and isopropoxy), butoxy (e.g., n-butoxy and tert-butoxy), and the like. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0985] As used herein, the term “amino” refers to a group of formula -NH2.

[0986] As used herein, the term “aryl,” employed alone or in combination with other terms, refers to an aromatic hydrocarbon group, which may be monocyclic or polycyclic (e.g., having 2, 3 or 4 fused rings). The term “Cn-maryl” refers to an aryl group having from n to m ring carbon atoms. Aryl groups include, e.g., phenyl, naphthyl, anthracenyl, phenanthrenyl, and the like. In some embodiments, aryl groups have from 5 to 10 carbon atoms. In some embodiments, the aryl group is phenyl or naphthyl. In some embodiments, the aryl is phenyl.

[0987] As used herein, “halo” refers to F, Cl, Br, or I. In some embodiments, a halo is F, Cl, or Br. In some embodiments, a halo is F or Cl. In some embodiments, a halo is F. In some embodiments, a halo is Cl.

[0988] As used herein, “Cn-mhaloalkoxy” refers to a group of formula -O-haloalkyl having n to m carbon atoms. Example haloalkoxy groups include OCF3 and OCHF2. In some54057-0036W01 / SNV0027-W01 PATENT

[0989] embodiments, the haloalkoxy group is fluorinated only. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0990] As used herein, the term “Cn-mhaloalkyl”, employed alone or in combination with other terms, refers to an alkyl group having from one halogen atom to 2s+l halogen atoms which may be the same or different, where “s” is the number of carbon atoms in the alkyl group, wherein the alkyl group has n to m carbon atoms. In some embodiments, the haloalkyl group is fluorinated only. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms. Example haloalkyl groups include CFs, C2F5, CHF2, CH2F, CCI3, CHCE, C2CI5 and the like.

[0991] As used herein, the term “Cn-malkylamino” refers to a group of formula -NH(alkyl), wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0992] As used herein, the term “Cn-malkoxycarbonyl” refers to a group of formula -C(O)O-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0993] As used herein, the term “Cn-malkylcarbonyl” refers to a group of formula -C(O)-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0994] As used herein, the term “Cn-malkylcarbonylamino” refers to a group of formula -NHC(O)-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0995] As used herein, the term “Cn-malkylsulfonylamino” refers to a group of

[0996] formula -NHS(O)2-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0997] As used herein, the term “aminosulfonyl” refers to a group of formula -S(O)2NH2. As used herein, the term “Cn-malkylaminosulfonyl” refers to a group of

[0998] formula -S(O)2NH(alkyl), wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0999] As used herein, the term “di(Cn-malkyl)aminosulfonyl” refers to a group of formula -S(O)2N(alkyl)2, wherein each alkyl group independently has n to m carbon atoms. In some embodiments, each alkyl group has, independently, 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[1000] As used herein, the term “aminosulfonylamino” refers to a group of formula - NHS(O)2NH254057-0036W01 / SNV0027-W01 PATENT

[1001] As used herein, the term “Cn-malkylaminosulfonylamino” refers to a group of formula -NHS(O)2NH(alkyl), wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[1002] As used herein, the term “di(Cn-malkyl)aminosulfonylamino” refers to a group of formula -NHS(O)2N(alkyl)2, wherein each alkyl group independently has n to m carbon atoms. In some embodiments, each alkyl group has, independently, 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[1003] As used herein, the term “aminocarbonylamino”, employed alone or in combination with other terms, refers to a group of formula -NHC(O)NH2.

[1004] As used herein, the term “Cn-malkylaminocarbonylamino” refers to a group of formula -NHC(O)NH(alkyl), wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[1005] As used herein, the term “di(Cn-malkyl)aminocarbonylamino” refers to a group of formula -NHC(O)N(alkyl)2, wherein each alkyl group independently has n to m carbon atoms. In some embodiments, each alkyl group has, independently, 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[1006] As used herein, the term “Cn-malkylcarbamyl” refers to a group of formula -C(O)-NH(alkyl), wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[1007] As used herein, the term “thio” refers to a group of formula -SH.

[1008] As used herein, the term “Cn-malkylthio” refers to a group of formula -S-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[1009] As used herein, the term “Cn-malkylsulfinyl” refers to a group of formula -S(O)-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[1010] As used herein, the term “Cn-malkylsulfonyl” refers to a group of formula -S(O)2-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[1011] As used herein, the term “amino” refers to a group of formula -NH2.

[1012] As used herein, the term “carbamyl” to a group of formula -C(O)NH2.

[1013] As used herein, the term “carbonyl”, employed alone or in combination with other terms, refers to a -C(O)- group.

[1014] As used herein, the term “cyano-Ci.3 alkyl” refers to a group of formula -(C1-3 alkylene) -CN.54057-0036W01 / SNV0027-W01 PATENT

[1015] As used herein, the term “HO-C1.3 alkyl” refers to a group of formula -(C1-3 alkylene)- OH.

[1016] As used herein, the term “C1-3 alkoxy-Ci-3 alkyl” refers to a group of formula -(C1-3 alkylene)-O(Ci-3 alkyl).

[1017] As used herein, the term “carboxy” refers to a group of formula -C(O)OH.

[1018] As used herein, the term “di(Cn-m-alkyl)amino” refers to a group of formula -N(alkyl)2, wherein the two alkyl groups each has, independently, n to m carbon atoms. In some embodiments, each alkyl group independently has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[1019] As used herein, the term “di(Cn-m-alkyl)carbamyl” refers to a group of formula -C(O)N(alkyl)2, wherein the two alkyl groups each has, independently, n to m carbon atoms. In some embodiments, each alkyl group independently has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[1020] As used herein, “cycloalkyl” refers to non-aromatic cyclic hydrocarbons including cyclized alkyl and alkenyl groups. Cycloalkyl groups can include mono- or polycyclic (e.g., having 2 fused rings) groups, spirocycles, and bridged rings (e.g., abridged bicycloalkyl group). Ring -forming carbon atoms of a cycloalkyl group can be optionally substituted by oxo or sulfido (e.g., C(O) or C(S)). Also included in the definition of cycloalkyl are moieties that have one or more aromatic rings fused (z.e., having a bond in common with) to the cycloalkyl ring, for example, benzo or thienyl derivatives of cyclopentane, cyclohexane, and the like. A cycloalkyl group containing a fused aromatic ring can be attached through any ring -forming atom including a ring -forming atom of the fused aromatic ring. Cycloalkyl groups can have 3, 4, 5, 6, 7, 8, 9, or 10 ring-forming carbons (z.e., C3-10). In some embodiments, the cycloalkyl is a C3- 10 monocyclic or bicyclic cycloalkyl. In some embodiments, the cycloalkyl is a C3-7 monocyclic cycloalkyl. In some embodiments, the cycloalkyl is a C4-7 monocyclic cycloalkyl. In some embodiments, the cycloalkyl is a C4-10 spirocycle or bridged cycloalkyl (e.g., a bridged bicycloalkyl group). Example cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptatrienyl, norbomyl, norpinyl, norcamyl, cubane, adamantane, bicyclo[l.1. l]pentyl, bicyclo[2.1. l]hexyl, bicyclo[2.2. l]heptanyl, bicyclo[3.1.1]heptanyl, bicyclo[2.2.2]octanyl, spiro[3.3]heptanyl, and the like. In some embodiments, cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[1021] As used herein, “heteroaryl” refers to a monocyclic or polycyclic (e.g., having 2 fused rings) aromatic heterocycle having at least one heteroatom ring member selected from N, O, S and B. In some embodiments, the heteroaryl ring has 1, 2, 3, or 4 heteroatom ring members independently selected from N, O, S and B. In some embodiments, any ring -forming N in a heteroaryl moiety can be an N-oxide. In some embodiments, the heteroaryl is a 5-1054057-0036W01 / SNV0027-W01 PATENT

[1022] membered monocyclic or bicyclic heteroaryl having 1, 2, 3, or 4 heteroatom ring members independently selected from N, O, S, and B. In some embodiments, the heteroaryl is a 5-, 7-, 8-, 9-, or 10-membered monocyclic or bicyclic heteroaryl having 1, 2, 3, or 4 heteroatom ring members independently selected from N, O, S, and B. In some embodiments, the heteroaryl is a 5-10 membered monocyclic or bicyclic heteroaryl having 1, 2, 3, or 4 heteroatom ring members independently selected from N, O, and S. In some embodiments, the heteroaryl is a 5-, 7-, 8-, 9-, or 10-membered monocyclic or bicyclic heteroaryl having 1, 2, 3, or 4 heteroatom ring members independently selected from N, O, and S. In some embodiments, the heteroaryl is a 5-6 membered monocyclic heteroaryl having 1 or 2 heteroatom ring members independently selected from N, O, S, and B. In some embodiments, the heteroaryl is a 5 membered monocyclic heteroaryl having 1 or 2 heteroatom ring members independently selected from N, O, S, and B. In some embodiments, the heteroaryl is a 5 membered monocyclic heteroaryl having 1 or 2 heteroatom ring members independently selected from N, O, and S. In some embodiments, the heteroaryl group contains 5 to 10, 5 to 7, 3 to 7, or 5 to 6 ring-forming atoms. In some embodiments, the heteroaryl group has 1 to 4 ring-forming heteroatoms, 1 to 3 ring-forming heteroatoms, 1 to 2 ring-forming heteroatoms or 1 ringforming heteroatom. When the heteroaryl group contains more than one heteroatom ring member, the heteroatoms may be the same or different. Example heteroaryl groups include, but are not limited to, thienyl (or thiophenyl), furyl (or furanyl), pyrrolyl, imidazolyl, thiazolyl, oxazolyl, pyrazolyl, isothiazolyl, isoxazolyl, 1,2,3-triazolyl, tetrazolyl, 1,2,3-thiadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-triazolyl, 1,2,4-thiadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-triazolyl, 1,3,4-thiadiazolyl, 1,3,4-oxadiazolyl and l,2-dihydro-l,2-azaborine, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, azolyl, triazolyl, thiadiazolyl, quinolinyl, isoquinolinyl, indolyl, benzothiophenyl, benzofuranyl, benzisoxazolyl, imidazofl, 2-b]thiazolyl, purinyl, triazinyl, thieno[3,2-b]pyridinyl, imidazo[l,2-a]pyridinyl, 1,5-naphthyridinyl, 1H-pyrazolo[4,3-b]pyridinyl, triazolo[4,3-a]pyridinyl, lH-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrazolo[l,5-a]pyridinyl, indazolyl, and the like.

[1023] As used herein, “heterocycloalkyl” refers to monocyclic or polycyclic heterocycles having at least one non-aromatic ring (saturated or partially unsaturated ring), wherein one or more of the ring-forming carbon atoms of the heterocycloalkyl is replaced by a heteroatom selected from N, O, S, and B, and wherein the ring-forming carbon atoms and heteroatoms of a heterocycloalkyl group can be optionally substituted by one or more oxo or sulfido (e.g., C(O), S(O), C(S), or S(O)2, etc.). When a ring -forming carbon atom or heteroatom of a heterocycloalkyl group is optionally substituted by one or more oxo or sulfide, the O or S of said group is in addition to the number of ring -forming atoms specified herein (e.g., a 1-methyl-6-oxo-l,6-dihydropyridazin-3-yl is a 6-membered heterocycloalkyl group, wherein a54057-0036W01 / SNV0027-W01 PATENT

[1024] ring-forming carbon atom is substituted with an oxo group, and wherein the 6-membered heterocycloalkyl group is further substituted with a methyl group). Heterocycloalkyl groups include monocyclic and polycyclic (e.g., having 2 fused rings) systems. Included in heterocycloalkyl are monocyclic and polycyclic 3 to 10, 4 to 10, 5 to 10, 4 to 7, 5 to 7, or 5 to 6 membered heterocycloalkyl groups. Heterocycloalkyl groups can also include spirocycles and bridged rings (e.g., a 5 to 10 membered bridged biheterocycloalkyl ring having one or more of the ring-forming carbon atoms replaced by a heteroatom independently selected from N, O, S, and B). The heterocycloalkyl group can be attached through a ring -forming carbon atom or a ring -forming heteroatom. In some embodiments, the heterocycloalkyl group contains 0 to 3 double bonds. In some embodiments, the heterocycloalkyl group contains 0 to 2 double bonds.

[1025] Also included in the definition of heterocycloalkyl are moieties that have one or more aromatic rings fused ( / . e., having a bond in common with) to the non -aromatic heterocyclic ring, for example, benzo or thienyl derivatives of piperidine, morpholine, azepine, etc. A heterocycloalkyl group containing a fused aromatic ring can be attached through any ringforming atom including a ring -forming atom of the fused aromatic ring.

[1026] In some embodiments, the heterocycloalkyl group contains 3 to 10 ring -forming atoms, 4 to 10 ring -forming atoms, 4 to 8 ring -forming atoms, 3 to 7 ring -forming atoms, or 5 to 6 ring -forming atoms. In some embodiments, the heterocycloalkyl group has 1 to 4 heteroatoms, 1 to 3 heteroatoms, 1 to 2 heteroatoms or 1 heteroatom. In some embodiments, the heterocycloalkyl is a monocyclic 4-6 membered heterocycloalkyl having 1 or 2 heteroatoms independently selected from N, O, S and B and having one or more oxidized ring members. In some embodiments, the heterocycloalkyl is a monocyclic or bicyclic 5-10 membered heterocycloalkyl having 1, 2, 3, or 4 heteroatoms independently selected from N, O, S, and B and having one or more oxidized ring members. In some embodiments, the heterocycloalkyl is a monocyclic or bicyclic 5 to 10 membered heterocycloalkyl having 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S and having one or more oxidized ring members. In some embodiments, the heterocycloalkyl is a monocyclic 5 to 6 membered heterocycloalkyl having 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S and having one or more oxidized ring members.

[1027] Example heterocycloalkyl groups include pyrrolidin-2-one (or 2-oxopyrrolidinyl), l,3-isoxazolidin-2-one, pyranyl, tetrahydropyran, oxetanyl, azetidinyl, morpholino, thiomorpholino, piperazinyl, tetrahydrofuranyl, tetrahydrothienyl, piperidinyl, pyrrolidinyl, isoxazolidinyl, isothiazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, imidazolidinyl, azepanyl, 1,2,3,4-tetrahydroisoquinoline, tetrahydrothiopheneyl, tetrahydrothiopheneyl 1,1-dioxide, benzazapene, azabicyclo[3.1.0]hexanyl, diazabicyclo[3.1.0]hexanyl,54057-0036W01 / SNV0027-W01 PATENT

[1028] oxobicyclo [2.1. l]hexanyl, azabicyclo [2.2. l]heptanyl, diazabicyclo [2.2. l]heptanyl, azabicyclo[3.1. l]heptanyl, diazabicyclo [3.1. l]heptanyl, azabicyclo[3.2. l]octanyl, diazabicyclo [3.2. l]octanyl, oxobicyclo [2.2.2] octanyl, azabicyclo[2.2.2]octanyl, azaadamantanyl, diazaadamantanyl, oxo-adamantanyl, azaspiro[3.3]heptanyl, 2-azaspiro[3.3]heptanyl, diazaspiro[3.3]heptanyl, azaspiro [3.5]nonanyl, 7-azaspiro[3.5]nonanyl, oxo-azaspiro[3.3]heptanyl, azaspiro[3.4]octanyl, diazaspiro[3.4]octanyl, oxo-azaspiro[3.4]octanyl, azaspiro [2.5] octanyl, diazaspiro[2.5]octanyl, azaspiro[4.4]nonanyl, diazaspiro[4.4]nonanyl, oxo-azaspiro[4.4]nonanyl, azaspiro[4.5]decanyl, diazaspiro[4.5]decanyl, diazaspiro[4.4]nonanyl, oxo-diazaspiro[4.4]nonanyl, oxo-dihydropyridazinyl, oxo-2,6-diazaspiro[3.4]octanyl, oxohexahydropyrrolo[l,2-a]pyrazinyl, 3-oxopiperazinyl, oxo-pyrrolidinyl, oxo-pyridinyl, and the like.

[1029] As used herein, “C0.pcycloalkyl-Cn-malkyl-” refers to a group of formula cycloalkylalkylene-, wherein the cycloalkyl has o to p carbon atoms and the alkylene linking group has n to m carbon atoms.

[1030] As used herein “C0.paryl-Cn-malkyl-” refers to a group of formula aryl-alkylene-, wherein the aryl has o to p carbon atoms and the alkylene linking group has n to m carbon atoms.

[1031] As used herein, “heteroaryl-Cn-malkyl-” refers to a group of formula heteroarylalkylene-, wherein alkylene linking group has n to m carbon atoms.

[1032] As used herein “heterocycloalkyl -Cn-malkyl-” refers to a group of formula heterocycloalkyl-alkylene-, wherein alkylene linking group has n to m carbon atoms.

[1033] As used herein, an “alkyl linking group” or “alkylene linking group” is a bivalent straight chain or branched alkyl linking group (“alkylene group”). For example, “C0.pcycloalkyl -Cn-m alkyl-”, “C0.paryl-Cn-malkyl-”, “phenyl-Cn-malkyl-”, “heteroaryl-Cn-malkyl-”, and “heterocycloalkyl-Cn-m alkyl-” contain alkyl linking groups. Examples of “alkyl linking groups” or “alkylene groups” include methylene, ethan- 1,1 -diyl, ethan- 1,2-diyl, propan-1,3-diyl, propan- 1,2-diyl, propan- 1,1 -diyl and the like.

[1034] As used herein, a “haloalkyl linking group” or “haloalkylene linking group” is a bivalent straight chain or branched haloalkyl linking group (“haloalkylene group”). Example haloalkylene groups include -CF2-, -C2F4-, -CHF-, -CCI2-, -CHC1-, -C2CI4-, and the like.

[1035] As used herein, a “cycloalkyl linking group” or “cycloalkylene linking group” is a bivalent straight chain or branched cycloalkyl linking group (“cycloalkylene group”).

[1036] Examples of “cycloalkyl linking groups” or “cycloalkylene groups” include cyclopropy-1,1,-diyl, cyclopropy- 1,2-diyl, cyclobut-l,3,-diyl, cyclopent-1, 3, -diyl, cyclopent- 1,4, -diyl, cyclohex- 1,2, -diyl, cyclohex-1, 3, -diyl, cyclohex- 1,4, -diyl, and the like.54057-0036W01 / SNV0027-W01 PATENT

[1037] As used herein, a “heterocycloalkyl linking group” or “heterocycloalkylene linking group” is a bivalent straight chain or branched heterocycloalkyl linking group (“heterocycloalkylene group”). Examples of “heterocycloalkyl linking groups” or “heterocycloalkylene groups” include azetidin-l,2-diyl, azetidin- 1,3 -diyl, pyrrolidin-l,2-diyl, pyrrolidin-l,3-diyl, pyrrolidin-2,3-diyl, piperidin-l,2-diyl, piperidin-l,3-diyl, piperidin-1,4-diyl, piperidin-2,3-diyl, piperidin-2,4-diyl, and the like.

[1038] As used herein, a “heteroaryl linking group” or “heteroarylene linking group” is a bivalent straight chain or branched heteroaryl linking group (“heteroarylene group”).

[1039] Examples of “heteroaryl linking groups” or “heteroarylene groups” include pyrazol-l,3-diyl, imidazol- 1,2, -diyl, pyridin-2,3-diyl, pyridin-2,4-diyl, pyridin-3,4-diyl, and the like.

[1040] At certain places, the definitions or embodiments refer to specific rings (e.g., an azetidine ring, a pyridine ring, etc.). Unless otherwise indicated, these rings can be attached to any ring member provided that the valency of the atom is not exceeded. For example, an azetidine ring may be attached at any position of the ring, whereas a pyridin-3-yl ring is attached at the 3 -position.

[1041] As used herein, the term “oxo” refers to an oxygen atom (z.e., =0) as a divalent substituent, forming a carbonyl group when attached to a carbon (e.g., C=O or C(O)), or attached to a nitrogen or sulfur heteroatom forming a nitroso, sulfinyl, or sulfonyl group.

[1042] As used herein, the term “independently selected from” means that each occurrence of a variable or substituent (e.g., each RG), are independently selected at each occurrence from the applicable list.

[1043] The compounds described herein can be asymmetric (e.g., having one or more stereocenters). All stereoisomers, such as enantiomers and diastereomers, are intended unless otherwise indicated. Compounds of the present disclosure that contain asymmetrically substituted carbon atoms can be isolated in optically active or racemic forms. Methods on how to prepare optically active forms from optically inactive starting materials are known in the art, such as by resolution of racemic mixtures or by stereoselective synthesis. Many geometric isomers of olefins, C=N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Cis and trans geometric isomers of the compounds of the present disclosure are described and may be isolated as a mixture of isomers or as separated isomeric forms. In some embodiments, the compound has the (A) -configuration. In some embodiments, the compound has the (^-configuration. The Formulas (e.g., Formula I, Formula II, etc.) provided herein include stereoisomers of the compounds.

[1044] Resolution of racemic mixtures of compounds can be carried out by any of numerous methods known in the art. An example method includes fractional recrystallizaion using a54057-0036W01 / SNV0027-W01 PATENT

[1045] chiral resolving acid which is an optically active, salt-forming organic acid. Suitable resolving agents for fractional recrystallization methods are, for example, optically active acids, such as the D and L forms of tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid or the various optically active camphorsulfonic acids such as P-camphorsulfonic acid. Other resolving agents suitable for fractional crystallization methods include stereoisomerically pure forms of a-methylbenzylamine (e.g., S and R forms, or diastereomerically pure forms), 2-phenylglycinol, norephedrine, ephedrine, N-methylephedrine, cyclohexylethylamine, 1,2-diaminocyclohexane, and the like.

[1046] Resolution of racemic mixtures can also be carried out by elution on a column packed with an optically active resolving agent (e.g., dinitrobenzoylphenylglycine). Suitable elution solvent composition can be determined by one skilled in the art.

[1047] Compounds provided herein also include tautomeric forms. Tautomeric forms result from the swapping of a single bond with an adjacent double bond together with the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge. Example prototropic tautomers include ketone - enol pairs, amide - imidic acid pairs, lactam - lactim pairs, enamine - imine pairs, and annular forms where a proton can occupy two or more positions of a heterocyclic system, for example, 1H- and 3H-imidazole, 1H-, 2H- and 4H-1,2,4-triazole, 1H- and 2H- isoindole, 2-hydroxypyridine and 2-pyridone, and 1H- and 2H-pyrazole. Tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution.

[1048] All compounds, and pharmaceutically acceptable salts thereof, can be found together with other substances such as water and solvents (e.g. hydrates and solvates) or can be isolated.

[1049] In some embodiments, preparation of compounds can involve the addition of acids or bases to affect, for example, catalysis of a desired reaction or formation of salt forms such as acid addition salts.

[1050] In some embodiments, the compounds provided herein, or salts thereof, are substantially isolated. By “substantially isolated” is meant that the compound is at least partially or substantially separated from the environment in which it was formed or detected. Partial separation can include, for example, a composition enriched in the compounds provided herein. Substantial separation can include compositions containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% by weight of the compounds provided herein, or salt thereof.54057-0036W01 / SNV0027-W01 PATENT

[1051] The term “compound” as used herein is meant to include all stereoisomers, geometric isomers, tautomers, and isotopes of the structures depicted. Compounds herein identified by name or structure as one particular tautomeric form are intended to include other tautomeric forms unless otherwise specified.

[1052] The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[1053] The present application also includes pharmaceutically acceptable salts of the compounds described herein. As used herein, “pharmaceutically acceptable salts” refers to derivatives of the disclosed compounds wherein the parent compound is modified by converting an existing acid or base moiety to its salt form. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts of the present disclosure include the conventional nontoxic salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. The pharmaceutically acceptable salts of the present disclosure can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, non-aqueous media like ether, ethyl acetate, alcohols (e.g., methanol, ethanol, iso-propanol, or butanol) or acetonitrile (ACN) are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418 and Journal of Pharmaceutical Science, 66, 2 (1977), each of which is incorporated herein by reference in its entirety.

[1054] Synthesis

[1055] Compounds of the present disclosure, including salts thereof, can be prepared using known organic synthesis techniques and can be synthesized according to numerous possible synthetic routes, such as those in the schemes below. The schemes below provide general guidance in connection with preparing the compounds of the present disclosure. One skilled in the art would understand that the preparations shown in the schemes can be modified or optimized using general knowledge of organic chemistry to prepare various compounds of the present disclosure. Provided compounds may generally be made by the processes described in the ensuing schemes and examples.54057-0036W01 / SNV0027-W01 PATENT

[1056] Compounds of Formula I, such as formula 1-5, can be synthesized, for example, using a process shown in Scheme I. Cross-coupling reactions (e.g. Suzuki reaction) of compound I-1 with appropriately substituted compound 1-2 can afford compounds of formula 1-3.

[1057] Compounds of formula 1-5 can be obtained by treating compounds of formula 1-3 with substituted compounds of formula 1-4 via suitable reactions (e.g., Suzuki reactions).

[1058] Scheme I.

[1059]

[1060] Compounds of Formula I (e.g., compounds of Formula II-5) can be prepared, for example, according to the procedures shown in Scheme II. Intermediate II-3 is prepared by a process comprising reacting compounds of formula II- 1 with II- 2 under Negishi coupling conditions. Compound II- 5 is prepared by a process comprising reacting intermediate II-3 with II-4 under a Suzuki coupling condition.

[1061] Scheme II.

[1062] LB— Znl

[1063]

[1064] 54057-0036W01 / SNV0027-W01 PATENT

[1065] Compounds of Formula I (e.g., compounds of Formula III-8) can be prepared, for example, according to the procedures shown in Scheme III. Compound III-l can be converted to III- 2 via Miyaura reaction with bis(pinacolato)diboron. Compound III-2 can then be converted to III-4 with III- 3 via the Suzuki reaction. Treating compound III-4 with boronate esters III-5 under Suzuki reaction condition then removal of the protecting group can lead to III-6. Reacting compound III-6 with III-7 via suitable reactions (e.g., alkylation or reductive amination) can afford compounds of formula III-8.

[1066] Scheme III.

[1067]

[1068] Compounds of Formula I (e.g., compounds of Formula IV-8) can be prepared, for example, according to the procedures shown in Scheme IV. Suzuki reaction of compound IV-1 with IV-2 can lead to IV-3. Compound IV-5 can be obtained by treating IV-3 with IV-4 via the Suzuki reaction. Deprotection of IV-5 with TFA can afford IV-6. Reaction of IV-6 and IV-7 under suitable conditions (i.e., alkylation or reductive amination) can afford compounds of formula I V-8.54057-0036W01 / SNV0027-W01 PATENT

[1069] Scheme IV.

[1070]

[1071] Compounds of Formula I (e.g., compounds of Formula V-13) can be prepared, for example, according to the procedures shown in Scheme V. Compound V-l can be converted to V-2 via condensation. V-2 can be converted to V-3 via Hemetsberger indole synthesis. Protection of V-3 with Boc anhydride, followed by reduction can afford compound V-5. V-5 can be converted to V-7 via SN2 reaction. Deprotection of V-7 can afford amine V-8.

[1072] Amidation of V-8 can afford spiro compound V-9. Compound V-ll can be obtained by treating V-9 with V-10 via Suzuki reaction. V-ll can be converted into compounds of formula V-13 via suitable reactions (e.g., Suzuki reaction).54057-0036W01 / SNV0027-W01 PATENT

[1073] Scheme V.

[1074]

[1075] Compounds of Formula I (e.g., compounds of Formula VI- 12) can be prepared, for example, using a process shown in Scheme VI. Compound VI-1 can be converted to VI-2 with suitable reagents (e.g., NaH and dimethyl carbonate). Contacting a compound of VI-2 with a reducing reagent (e.g.. NaBH ) can lead to compound VI-3, which can be converted to VI-4 with suitable reagents (e.g., MsCl and EtsN). Compound VI-5 can be obtained by treating compound VI-4 with suitable reagent in the presence of suitable bases (e.g.

[1076] NaHMDS). Hydrolysis of compound VI-5 can lead to compound VI-6. Compound VI-8 can be obtained by treating compound VI-6 with amine VI-7 via suitable reagents (e.g., HATU and DIPEA). Contacting compound VI-8 with compound VI-9 under suitable conditions (e.g., alkylation, reductive amination, cross-coupling reactions) can afford compound VI-10. Compounds of formula VI- 12 can be obtained by treating compounds of formula VI- 10 with substituted compounds of formula VI-11 via suitable reactions (e.g., Suzuki reactions).54057-0036W01 / SNV0027-W01 PATENT

[1077] Scheme VI.

[1078]

[1079] Compounds of Formula I (e.g., compounds of Formula VII-18) can be prepared, for example, using a process shown in Scheme VII. Compound VII-1 can be converted to VII-3 in the presence of compound VII-2 with suitable reagents (e.g., pyrrolidine and TiCF).

[1080] Compound VII-4 can be obtained by contacting a compound of VII-3 with suitable reagents (e.g., BOC2O and pyridine). Compound VII-4 can be converted to VII-6 in the presence of compound VII-5 with suitable reagents (e.g., w-BuLi). Deprotection of compound VII-6 with suitable reagents (e.g., TFA) can lead to compound VII-7. Halogenation of compound VII-7 can lead to compound VII-8 with suitable reagents (e.g., NBS or NIS), which can be converted to compound VII-9 with suitable reagents (e.g., PhSCFCI and NaH). Compound VII-10 can be obtained by treating compound VII-9 with suitable reagents (e.g., (tributylstannyl)methanol and Pd(dppf)Ch), which can be converted to compound VII-11 with suitable reagents (MsCl, EtsN). Contacting compound VII-11 with compound VII-12 under suitable conditions (e.g., LDA) can afford compound VII-13. Compounds of formula VII-15 can be obtained by treating compounds of formula VII-13 with substituted compounds of formula VII- 14 via suitable reactions (e.g., Suzuki reactions). Compounds of formula VII-17 can be obtained by treating compounds of formula VII-15 with substituted54057-0036W01 / SNV0027-W01 PATENT

[1081] compounds of formula VII-16 via suitable conditions (e.g., reductive amination or SN2 reactions). Deprotection of compound VII- 17 can lead to compound VII- 18 with suitable reagents (e.g., NaOH).

[1082] Scheme VII.

[1083]

[1084] Compounds of Formula I (e.g., compounds of Formula VIII-14) can be prepared, for example, using a process shown in Scheme VIII. Aldehyde VIII-1 can be converted to VIII-3 via a condensation reaction with azide VIII-2. VIII-3 can be converted to VIII-4 via Hemetsberger indole synthesis. Compound VIII-5 can be converted to VIII-6 via suitable reactions (e.g., transition metal -catalyzed cross-coupling reactions). VIII-7 can be obtained from VIII-6 via Miyaura reaction. Treating VIII-7 with VIII-4 can afford VIII-8 via Suzuki reaction. Removal of protecting group in VIII-8 can provide alcohol VIII-9. Intramolecular cyclization of VIII-9 can lead to compound VIII-10. Suzuki coupling of VIII-10 with VIII-11 can afford VIII-12. Reacting of VIII-12 with VIII-13 under suitable conditions (i.e., cross-coupling conditions) can provide compounds of formula VIII-14.54057-0036W01 / SNV0027-W01 PATENT

[1085] Scheme VIII.

[1086]

[1087] Compounds of Formula I (e.g., compounds of Formula IX-11) can be prepared, for example, according to the procedures shown in Scheme IX. Intermediate IX-2 can be prepared by a process comprising reacting compounds of formula IX-1 with suitable reagents (e.g., BOC2O, PMB-Br). Intermediate IX-3 can be prepared by reacting intermediate IX-2 with suitable reagents (e.g., NBS, NIS). Intermediate IX-4 can be prepared by reacting intermediate IX-3 under a Stille coupling condition (e.g., Pd(PPhs)4, BiisSn Ally 1 ).

[1088] Intermediate IX-5 can be prepared by reacting intermediate IX-4 with suitable reagents (e.g., OsO4, NalC ). Intermediate IX-6 can be prepared by reacting intermediate IX-5 with suitable reagents (e.g., McNFF. STAB). Intermediate IX-8 can be prepared by reacting intermediate IX-6 with IX-7 under a Suzuki coupling condition. Compound IX-10 can be prepared by reacting intermediate IX-8 with IX-9 under a Suzuki coupling condition. Compound IX-11 can be prepared by removal of the protecting group in intermediate IX-10 with suitable reagents (e.g., TFA).54057-0036W01 / SNV0027-W01 PATENT

[1089] Scheme IX.

[1090]

[1091] Compounds of Formula I (e.g., compounds of Formula X-14) can be prepared, for example, according to the procedures shown in Scheme X. Compound X-l can be converted to hydrazine X-2 via diazotization and reduction. X-2 can be converted to indole X-4 via Fisher indole synthesis. Compound X-6 can be obtained by treating X-4 with X-5 via Suzuki coupling. Protection of X-6, followed by hydrogenation and deprotection, can afford diol X-9. X-9 can be converted to X-10 via the Mitsunobu reaction. X-10 can be converted to X-ll via deprotection then suitable reactions (e.g., amidation). Treating X-ll with X-12 can give X-13 via Suzuki reaction. Deprotection of X-13 can afford compounds of formula X-14 via suitable reagents (e.g., TFA).54057-0036W01 / SNV0027-W01 PATENT

[1092] Scheme X.

[1093]

[1094] Compounds of Formula I (e.g., compounds of Formula XI-7) can be prepared, for example, according to the procedures shown in Scheme XI. Intermediate XI-3 can be prepared by Suzuki coupling of compounds of formula XI-1 with XI-2. Intermediate XI-5 can be prepared from intermediate XI-3 and XI-4 under a Suzuki coupling condition.

[1095] Intermediate XI-6 can be prepared by reacting intermediate XI-5 with suitable reagents (e.g., NaOH, SOCh, PBrs). Intramolecular cyclization of intermediate XI-6 with suitable reagents can afford compound XI-7.54057-0036W01 / SNV0027-W01 PATENT

[1096] Scheme XI.

[1097]

[1098] The reactions for preparing compounds of the invention can be carried out in suitable solvents which can be readily selected by one of skill in the art of organic synthesis. Suitable solvents can be substantially nonreactive with the starting materials (reactants), the intermediates, or products at the temperatures at which the reactions are carried out, e.g., temperatures which can range from the solvent's freezing temperature to the solvent's boiling temperature. A given reaction can be carried out in one solvent or a mixture of more than one solvent. Depending on the particular reaction step, suitable solvents for a particular reaction step can be selected by the skilled artisan.

[1099] Preparation of compounds of the invention can involve the protection and deprotection of various chemical groups. The need for protection and deprotection, and the selection of appropriate protecting groups, can be readily determined by one skilled in the art. The chemistry of protecting groups can be found, for example, in T. W. Greene and P. G. M.

[1100] Wuts, Protective Groups in Organic Synthesis, 3rd. Ed., Wiley & Sons, Inc., New York (1999), which is incorporated herein by reference in its entirety.

[1101] Reactions can be monitored according to any suitable method known in the art. For example, product formation can be monitored by spectroscopic means, such as nuclear magnetic resonance spectroscopy (e.g., ’H or13C), infrared spectroscopy, spectrophotometry (e.g., UV-visible), or mass spectrometry, or by chromatography such as high performance liquid chromatography (HPLC) or thin layer chromatography.54057-0036W01 / SNV0027-W01 PATENT

[1102] The expressions, “ambient temperature,” “room temperature,” and “r.t ”, as used herein, are understood in the art, and refer generally to a temperature, e.g. a reaction temperature, that is about the temperature of the room in which the reaction is carried out, for example, a temperature from about 20 °C to about 30 °C.

[1103] Methods of Use

[1104] The present disclosure provides uses for compounds and compositions described herein. The compounds described herein can inhibit the activity of signal transducer and activator of transcription 6 (STAT6). In some embodiments, provided compounds and compositions are for use in medicine (e.g., as therapy). In some embodiments, provided compounds and compositions are useful in treating a disease, disorder, or condition, wherein an underlying pathology is, wholly or partially, mediated by STAT6. In some embodiments, provided compounds and compositions are useful in research as, for example, analytical tools and / or control compounds in biological assays.

[1105] Recent genetic studies revealed that germline heterozygous gain-of-function STAT6 variants caused severe allergic disease in humans (see e.g., J. Exp. Med. 2023;220(5): e20221755). Similarly, transgenic mice with gain-of-function mutation of the Stat6 gene spontaneously developed dermatitis with skin thickening and eosinophil infdtration (see e.g., J. Allergy Clin. Immunol. 2023; 151(5): 1402-1409], Stotd-deficient mice were viable and fertile with no behavioral abnormalities, but their lymphocytes failed to respond to interleukin-4 (IL-4) stimulation (see e.g., Immunity. 1996;4(3):313-319).

[1106] The STAT6 signaling pathway involves cytokines IL-4 and IL-13, the Janus kinase (JAK) proteins, and STAT6 transcription factor. Genetic studies and clinical trials have demonstrated that STAT6 signaling cascade is central to pro-allergic immune responses. Molecules to block this pathway have been successfully used for treating autoimmune and chronic inflammatory diseases in patients. Dual inhibition of IL-4 and IL- 13 with dupilumab has been approved for treatment of asthma, atopic dermatitis, and chronic sinusitis with nasal polyposis (see e.g., Allergy. 2020;75(5): 1188-1204). Blockade of JAK have also demonstrated an excellent efficacy in atopic dermatitis, asthma, and food allergy (see e.g., Nat. Rev. DrugDiscov. 2017;16(12):843-862). STAT6 is further downstream of the pathway and targeting STAT6 is expected to have a better selectivity that leads to an improved therapeutic index.

[1107] STAT6 protein consists of several key domains including an N-terminal coiled-coil domain, a DNA-binding domain (DBD), a linker region, a Src homology 2 (SH2) domain, and a C-terminal transactivation domain (TAD), with the SH2 domain playing a crucial role in dimerization and the TAD responsible for transcriptional activation upon cytokine54057-0036W01 / SNV0027-W01 PATENT

[1108] signaling. The SH2 domain is critical for dimerization of STAT6 molecules after phosphorylation on a specific tyrosine residue, enabling the activated complex to translocate to the nucleus. Targeting SH2 domain of STAT6 with a small-molecule inhibitor was effective in mice model of allergic airway disease (see e.g., J Biol. Chem.

[1109] 2018;293(26): 10026-10040). Targeting the SH2 domain, however, is a challenging task for small molecule drug discovery. SH2 domains are highly conserved across many proteins, making it difficult to design a small molecule that specifically targets one SH2 domain without affecting others. In addition, the nature of the SH2 domain, which binds to a phosphorylated tyrosine residue, requires a very specific molecular interaction that can be hard to mimic with a small molecule inhibitor. An alternative approach to target STAT6 is to deplete this protein using molecular glue or the proteolysis targeting chimera (PROTAC) technology. Targeted degradation of STAT6 with a small molecule degrader effectively and selectively reduces the levels of STAT6 protein in cells and depletes STAT6 protein in mouse tissues (see e.g., J Med Chem. 2024; DOI: 10.1021 / acs.jmedchem.4c01009).

[1110] Accordingly, the present disclosure provides methods of treating a variety of human diseases associated with STAT6, including allergic inflammatory diseases, chronic inflammatory diseases, autoimmune diseases, and multiple types of cancers. In some embodiments, the present application provides a method of treating a disease or disorder (e.g., associated with STAT6), wherein the disease or disorder is selected from an allergic inflammatory disease, a chronic inflammatory disease, an autoimmune disease, and cancer, comprising administering a compound, or pharmaceutically acceptable salt thereof, or composition provided herein, to a subject in need thereof.

[1111] Exemplary allergic inflammatory diseases include, but are not limited to, atopic dermatitis, allergic rhinitis, asthma, eosinophilic esophagitis, chronic rhinosinusitis with nasal polyps, urticaria, anaphylaxis, and food allergies. In some embodiments, the method is a method of treating an allergic inflammatory disease. In some embodiments, the allergic inflammatory disease is selected from atopic dermatitis, allergic rhinitis, asthma, eosinophilic esophagitis, chronic rhinosinusitis with nasal polyps, urticaria, anaphylaxis, and food allergy.

[1112] Exemplary chronic inflammatory or autoimmune diseases include, but are not limited to, rheumatoid arthritis, pulmonary fibrosis, and multiple sclerosis. In some embodiments, the method is a method of treating a chronic inflammatory or autoimmune disease. In some embodiments, the chronic inflammatory or autoimmune disease is selected from rheumatoid arthritis, pulmonary fibrosis, and multiple sclerosis.

[1113] Exemplary cancers include, but are not limited to, blood cancers (e.g., follicular lymphoma, primary mediastinal B-cell lymphoma, leukemia, multiple myeloma, mantle cell lymphoma, acute lymphocytic leukemia, chronic lymphocytic leukemia, B-cell lymphoma, T-54057-0036W01 / SNV0027-W01 PATENT

[1114] cell lymphoma, Hodgkin's lymphoma, and non-Hodgkin's lymphoma, hairy cell lymphoma) and multiple solid tissue cancers including breast, pancreatic, prostate, colorectal, endometrial, intestinal, and skin cancer.

[1115] In some embodiments, the method is a method of treating cancer. In some embodiments, the cancer is selected from breast cancer, pancreatic cancer, prostate cancer, colorectal cancer, endometrial cancer, intestinal cancer, and skin cancer.

[1116] In some embodiments, the cancer is a blood cancer. In some embodiments, the blood cancer is selected from leukemia, lymphoma, and multiple myeloma. In some embodiments, the blood cancer is selected from follicular lymphoma, primary mediastinal B-cell lymphoma, leukemia, multiple myeloma, mantle cell lymphoma, acute lymphocytic leukemia, chronic lymphocytic leukemia, B-cell lymphoma, T-cell lymphoma, Hodgkin's lymphoma, and non-Hodgkin's lymphoma, hairy cell lymphoma.

[1117] The compounds, pharmaceutically acceptable salts thereof, and compositions of the present disclosure are expected to suppress the STAT6 signaling pathway, leading to therapeutic benefits in treating diseases particularly allergic inflammatory diseases, chronic inflammatory diseases, and cancers driven by overactivation of the STAT6 pathway.

[1118] In some embodiments, provided herein is a method of increasing survival or progression-free survival in a patient, comprising administering a compound provided herein to the patient. In some embodiments, the patient has cancer. In some embodiments, the patient has a disease or disorder described herein. As used herein, progression-free survival refers to the length of time during and after the treatment of a solid tumor that a patient lives with the disease but it does not get worse. Progression-free survival can refer to the length of time from first administering the compound until the earlier of death or progression of the disease. Progression of the disease can be defined by RECIST v. 1.1 (Response Evaluation Criteria in Solid Tumors), as assessed by an independent centralized radiological review committee. In some embodiments, administering of the compound results in a progression free survival that is greater than about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 8 months, about 9 months, about 12 months, about 16 months, or about 24 months. In some embodiments, the administering of the compound results in a progression free survival that is at least about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 8 months, about 9 months, or about 12 months; and less than about 24 months, about 16 months, about 12 months, about 9 months, about 8 months, about 6 months, about 5 months, about 4 months, about 3 months, or about 2 months. In some embodiments, the administering of the compound results in an increase of progression free survival that is at least about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 8 months, about 9 months, or about 1254057-0036W01 / SNV0027-W01 PATENT

[1119] months; and less than about 24 months, about 16 months, about 12 months, about 9 months, about 8 months, about 6 months, about 5 months, about 4 months, about 3 months, or about 2 months.

[1120] The present disclosure further provides a compound described herein, or a pharmaceutically acceptable salt thereof, for use in any of the methods described herein.

[1121] The present disclosure further provides use of a compound described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for use in any of the methods described herein.

[1122] As used herein, the term “cell” is meant to refer to a cell that is in vitro, ex vivo or in vivo. In some embodiments, an ex vivo cell can be part of a tissue sample excised from an organism such as a mammal. In some embodiments, an in vitro cell can be a cell in a cell culture. In some embodiments, an in vivo cell is a cell living in an organism such as a mammal.

[1123] As used herein, the term “contacting” refers to the bringing together of indicated moieties in an in vitro system or an in vivo system. For example, “contacting” STAT6 with a compound described herein includes the administration of a compound described herein to an individual or patient, such as a human, having STAT6, as well as, for example, introducing a compound described herein into a sample containing a cellular or purified preparation containing the STAT6.

[1124] As used herein, the term “individual” or “patient,” used interchangeably, refers to any animal, including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, and most preferably humans.

[1125] As used herein, the phrase “therapeutically effective amount” refers to the amount of active compound or pharmaceutical agent such as an amount of any of the solid forms or salts thereof as disclosed herein that elicits the biological or medicinal response in a tissue, system, animal, individual or human that is being sought by a researcher, veterinarian, medical doctor or other clinician. An appropriate "effective" amount in any individual case may be determined using techniques known to a person skilled in the art.

[1126] The phrase “pharmaceutically acceptable” is used herein to refer to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, immunogenicity or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[1127] As used herein, the phrase “pharmaceutically acceptable carrier or excipient” refers to a pharmaceutically-acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, solvent, or encapsulating material. Excipients or carriers are generally safe,54057-0036W01 / SNV0027-W01 PATENT

[1128] non-toxic and neither biologically nor otherwise undesirable and include excipients or carriers that are acceptable for veterinary use as well as human pharmaceutical use. In one embodiment, each component is “pharmaceutically acceptable” as defined herein. See, e.g, Remington: The Science and Practice of Pharmacy 21st ed.; Lippincott Williams & Wilkins: Philadelphia, Pa., 2005; Handbook of Pharmaceutical Excipients, 6th ed.; Rowe et al., Eds.; The Pharmaceutical Press and the American Pharmaceutical Association: 2009; Handbook of Pharmaceutical Additives, 3rd ed.; Ash and Ash Eds.; Gower Publishing Company: 2007; Pharmaceutical Preformulation and Formulation, 2nd ed.; Gibson Ed.; CRC Press LLC: Boca Raton, Fla., 2009.

[1129] As used herein, the term “treating” or “treatment” refers to inhibiting the disease; for example, inhibiting a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., arresting further development of the pathology and / or symptomatology) or ameliorating the disease; for example, ameliorating a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., reversing the pathology and / or symptomatology) such as decreasing the severity of disease.

[1130] In some embodiments, the compounds of the invention are useful in preventing or reducing the risk of developing any of the diseases referred to herein; e.g., preventing or reducing the risk of developing a disease, condition or disorder in an individual who may be predisposed to the disease, condition or disorder but does not yet experience or display the pathology or symptomatology of the disease.

[1131] It is appreciated that certain features of the disclosure, which are, for clarity, described in the context of separate embodiments, can also be provided in combination in a single embodiment (while the embodiments are intended to be combined as if written in multiply dependent form). Conversely, various features of the disclosure which are, for brevity, described in the context of a single embodiment, can also be provided separately or in any suitable subcombination.

[1132] Combination Therapies

[1133] In some embodiments, the compound, salt, or composition provided herein is administered as part of a combination therapy. As used herein, the term “combination therapy” refers to those situations in which a subject is simultaneously exposed to two or more therapeutic or prophylactic regimens (e.g., two or more therapeutic or prophylactic agents). When used for allergic inflammatory diseases, exemplary additional therapies include, but are not limited to, antihistamines, immunotherapies, and nonsteroidal anti-54057-0036W01 / SNV0027-W01 PATENT

[1134] inflammatory drugs (NSAIDs), and other standard of care therapies. When used for treating cancer, exemplary additional therapies include, but are not limited to, chemotherapies, radiotherapies, immune -oncology agents, and other targeted cancer therapies.

[1135] In some embodiments, one or more additional therapeutic agents such as, for example, antihistamines, immunotherapies, and nonsteroidal anti-inflammatory drugs (NSAIDs), other standard of care therapies, chemotherapies, radiotherapies, immune-oncology agents, and other targeted cancer therapies useful for treating diseases associated with STAT6 can be used in combination with the compounds and salts provided herein. The agents can be combined with the present compounds in a single dosage form, or the agents can be administered simultaneously or sequentially as separate dosage forms.

[1136] In some embodiments, the present application provides a method of treating atopic dermatitis comprising administering a compound or composition provided herein and one or more additional therapeutic agents. In some embodiments, the one or more additional therapeutic agents useful for the treatment of atopic dermatitis include, but are not limited to, topical corticosteroids, topical calcineurin inhibitors (e.g., pimecrolimus, tacrolimus), emollients for moisturization, and systemic medications (e.g., dupilumab, tralokinumab, lebrikizumab), and JAK inhibitors (e.g., baricitinib, upadacitinib, abrocitinib).

[1137] In some embodiments, the present application provides a method of treating asthma comprising administering a compound or composition provided herein and one or more additional therapeutic agents. In some embodiments, the one or more additional therapeutic agents useful for the treatment of asthma include, but are not limited to, inhaled corticosteroids (e.g., fluticasone, budesonide, mometasone, beclomethasone, ciclesonide, symbicort), and biologies (e.g., omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, tezepelumab).

[1138] In some embodiments, the present application provides a method of treating chronic rhinosinusitis with nasal polyposis comprising administering a compound or composition provided herein and one or more additional therapeutic agents. In some embodiments, the one or more additional therapeutic agents useful for the treatment of chronic rhinosinusitis with nasal polyposis include, but are not limited to, dupilumab, omalizumab, and mepolizumab.

[1139] In some embodiments, the present application provides a method of treating eosinophilic esophagitis comprising administering a compound or composition provided herein and one or more additional therapeutic agents. In some embodiments, the one or more additional therapeutic agents useful for the treatment of eosinophilic esophagitis include, but are not limited to, budesonide and dupilumab.

[1140] In some embodiments, the present application provides a method of treating prurigo nodularis comprising administering a compound or composition provided herein and one or54057-0036W01 / SNV0027-W01 PATENT

[1141] more additional therapeutic agents. In some embodiments, the one or more additional therapeutic agents useful for the treatment of prurigo nodularis include, but are not limited to, nemolizumab and dupilumab.

[1142] In some embodiments, the present application provides a method of treating rheumatoid arthritis comprising administering a compound or composition provided herein and one or more additional therapeutic agents. In some embodiments, the one or more additional therapeutic agents useful for the treatment of rheumatoid arthritis include, but are not limited to, corticosteroids (e.g., prednisone, methylprednisolone, hydrocortisone, triamcinolone), nonsteroidal anti-inflammatory drugs (e.g., ibuprofen, naproxen, celecoxib, diclofenac, etodolac, fenoprofen, flurbiprofen, indomethacin, ketoprofen, ketorolac), diseasemodifying antirheumatic drugs (e.g., methotrexate, hydroxychloroquine, sulfasalazine, leflunomide, etanercept, adalimumab, infliximab), and JAK inhibitors.

[1143] In some embodiments, the present application provides a method of treating pulmonary fibrosis comprising administering a compound or composition provided herein and one or more additional therapeutic agents. In some embodiments, the one or more additional therapeutic agents useful for the treatment of pulmonary fibrosis, include, but are not limited to, anti -fibrotic agents (e.g., pirfenidone, nintedanib).

[1144] In some embodiments, the present application provides a method of treating multiple sclerosis comprising administering a compound or composition provided herein and one or more additional therapeutic agents. In some embodiments, the one or more additional therapeutic agents useful for the treatment of multiple sclerosis, include, but are not limited to, teriflunomide, dimethyl fumarate, diroximel fumarate, fmgolimod, siponimod, cladribine, ocrelizumab, and natalizumab.

[1145] In some embodiments, the present application provides a method of treating cancer (e.g., a cancer associated with STAT6 pathway) comprising administering a compound or composition provided herein and one or more additional therapeutic agents. In some embodiments, the one or more additional therapeutic agents useful for the treatment of cancer include, but are not limited to, chemotherapies including platinum -based therapy, taxane-based therapy, albumin bound paclitaxel, altretamine, capecitabine, cyclophosphamide, gemcitabine, ifosfamide, irinotecan, liposomal doxorubicin, melphalan, pemetrexed, topotecan, vinorelbine, radiotherapies, immunotherapies including antibodies of PD1, PD-L1, and CTLA4, and antibody drug conjugates.

[1146] Exemplary targeted cancer therapies include, but are not limited to, BTK inhibitors, BCL2 inhibitors, PI3K inhibitors, KRAS inhibitors, CDK4 / 6 inhibitors, PARP inhibitors, BRAF inhibitors, MEK inhibitors, HIF inhibitors, androgen receptor inhibitors, selective estrogen receptor modulators, proteosome inhibitors, mTOR inhibitors, EGFR inhibitors,54057-0036W01 / SNV0027-W01 PATENT

[1147] FGFR inhibitors, MET inhibitors, PDGFR inhibitors, VEGFR inhibitors, and EZH2 inhibitors.

[1148] In some embodiments, the additional therapeutic agent is administered simultaneously with a compound or salt provided herein. In some embodiments, the additional therapeutic agent is administered after administration of the compound or salt provided herein. In some embodiments, the additional therapeutic agent is administered prior to administration of the compound or salt provided herein. In some embodiments, the compound or salt provided herein is administered during a surgical procedure. In some embodiments, the compound or salt provided herein is administered in combination with an additional therapeutic agent during a surgical procedure.

[1149] Methods for the safe and effective administration of most of these chemotherapeutic agents are known to those skilled in the art. In addition, their administration is described in the standard literature. For example, the administration of many of the chemotherapeutic agents is described in the “Physicians’ Desk Reference” (PDR, e.g., 1996 edition, Medical Economics Company, Montvale, NJ), the disclosure of which is incorporated herein by reference as if set forth in its entirety.

[1150] In some embodiments, the additional therapeutic agent is administered simultaneously with a compound or salt provided herein. In some embodiments, the additional therapeutic agent is administered after administration of the compound or salt provided herein. In some embodiments, the additional therapeutic agent is administered prior to administration of the compound or salt provided herein. In some embodiments, the compound or salt provided herein is administered during a surgical procedure. In some embodiments, the compound or salt provided herein is administered in combination with an additional therapeutic agent during a surgical procedure.

[1151] As provided herein, the additional compounds, inhibitors, agents, etc. can be combined with the compounds provided herein in a single or continuous dosage form, or they can be administered simultaneously or sequentially as separate dosage forms.

[1152] Pharmaceutical Formulations and Dosage Forms

[1153] When employed as pharmaceuticals, the compounds of the invention can be administered in the form of pharmaceutical compositions which refers to a combination of a compound of the invention, or its pharmaceutically acceptable salt, and at least one pharmaceutically acceptable carrier. These compositions can be prepared in a manner well known in the pharmaceutical art, and can be administered by a variety of routes, depending upon whether local or systemic treatment is desired and upon the area to be treated.

[1154] Administration may be topical (including ophthalmic and to mucous membranes including54057-0036W01 / SNV0027-W01 PATENT

[1155] intranasal, vaginal and rectal delivery), pulmonary (e.g., by inhalation or insufflation of powders or aerosols, including by nebulizer; intratracheal, intranasal, epidermal and transdermal), ocular, oral or parenteral. Methods for ocular delivery can include topical administration (eye drops), subconjunctival, periocular or intravitreal injection or introduction by balloon catheter or ophthalmic inserts surgically placed in the conjunctival sac. Parenteral administration includes intravenous, intraarterial, subcutaneous, intraperitoneal, or intramuscular injection or infusion; or intracranial, e.g., intrathecal or intraventricular, administration. Parenteral administration can be in the form of a single bolus dose, or may be, for example, by a continuous perfusion pump. Pharmaceutical compositions and formulations for topical administration may include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable.

[1156] This invention also includes pharmaceutical compositions which contain, as the active ingredient, one or more of the compounds of the invention above in combination with one or more pharmaceutically acceptable carriers. In making the compositions of the invention, the active ingredient is typically mixed with an excipient, diluted by an excipient or enclosed within such a carrier in the form of, for example, a capsule, sachet, paper, or other container. When the excipient serves as a diluent, it can be a solid, semi-solid, or liquid material, which acts as a vehicle, carrier or medium for the active ingredient. Thus, the compositions can be in the form of tablets, pills, powders, lozenges, sachets, cachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols (as a solid or in a liquid medium), ointments containing, for example, up to 10 % by weight of the active compound, soft and hard gelatin capsules, suppositories, sterile injectable solutions, and sterile packaged powders.

[1157] In preparing a formulation, the active compound can be milled to provide the appropriate particle size prior to combining with the other ingredients. If the active compound is substantially insoluble, it can be milled to a particle size of less than 200 mesh. If the active compound is substantially water soluble, the particle size can be adjusted by milling to provide a substantially uniform distribution in the formulation, e.g. about 40 mesh.

[1158] The active compound can be effective over a wide dosage range and is generally administered in a pharmaceutically effective amount. It will be understood, however, that the amount of the compound actually administered will usually be determined by a physician, according to the relevant circumstances, including the condition to be treated, the chosen route of administration, the actual compound administered, the age, weight, and response of the individual patient, the severity of the patient's symptoms, and the like.

[1159] For preparing solid compositions such as tablets, the principal active ingredient is mixed with a pharmaceutical excipient to form a solid pre -formulation composition54057-0036W01 / SNV0027-W01 PATENT

[1160] containing a homogeneous mixture of a compound of the present invention. When referring to these pre -formulation compositions as homogeneous, the active ingredient is typically dispersed evenly throughout the composition so that the composition can be readily subdivided into equally effective unit dosage forms such as tablets, pills and capsules. This solid pre -formulation is then subdivided into unit dosage forms of the type described above.

[1161] The tablets or pills of the present invention can be coated or otherwise compounded to provide a dosage form affording the advantage of prolonged action. For example, the tablet or pill can comprise an inner dosage and an outer dosage component, the latter being in the form of an envelope over the former. The two components can be separated by an enteric layer which serves to resist disintegration in the stomach and permit the inner component to pass intact into the duodenum or to be delayed in release.

[1162] The liquid forms in which the compounds and compositions of the present invention can be incorporated for administration orally or by injection include aqueous solutions, suitably flavored syrups, aqueous or oil suspensions, and flavored emulsions with edible oils.

[1163] The compositions for inhalation or insufflation include solutions and suspensions in pharmaceutically acceptable, aqueous or organic solvents, or mixtures thereof, and powders. The liquid or solid compositions may contain suitable pharmaceutically acceptable excipients as described supra. In some embodiments, the compositions are administered by the oral or nasal respiratory route for local or systemic effect. Compositions in can be nebulized by use of inert gases. Nebulized solutions may be breathed directly from the nebulizing device or the nebulizing device can be attached to a face masks tent, or intermittent positive pressure breathing machine. Solution, suspension, or powder compositions can be administered orally or nasally from devices which deliver the formulation in an appropriate manner

[1164] The amount of compound or composition administered to a patient will vary depending upon what is being administered, the purpose of the administration, such as prophylaxis or therapy, the state of the patient, the manner of administration, and the like. In therapeutic applications, compositions can be administered to a patient already suffering from a disease in an amount sufficient to cure or at least partially arrest the symptoms of the disease and its complications. Effective doses will depend on the disease condition being treated as well as by the judgment of the attending clinician depending upon factors such as the severity of the disease, the age, weight and general condition of the patient, and the like.

[1165] The compositions administered to a patient can be in the form of pharmaceutical compositions described above. These compositions can be sterilized by conventional sterilization techniques, or may be sterile filtered. Aqueous solutions can be packaged for use as is, or lyophilized, the lyophilized preparation being combined with a sterile aqueous carrier prior to administration. The pH of the compound preparations typically will be between 3 and54057-0036W01 / SNV0027-W01 PATENT

[1166] 11, more preferably from 5 to 9 and most preferably from 7 to 8. It will be understood that use of certain of the foregoing excipients, carriers, or stabilizers will result in the formation of pharmaceutical salts.

[1167] The therapeutic dosage of the compounds of the present invention can vary according to, for example, the particular use for which the treatment is made, the manner of administration of the compound, the health and condition of the patient, and the judgment of the prescribing physician. The proportion or concentration of a compound of the invention in a pharmaceutical composition can vary depending upon a number of factors including dosage, chemical characteristics (e.g., hydrophobicity), and the route of administration. The dosage is likely to depend on such variables as the type and extent of progression of the disease or disorder, the overall health status of the particular patient, the relative biological efficacy of the compound selected, formulation of the excipient, and its route of administration. Effective doses can be extrapolated from dose-response curves derived from in vitro or animal model test systems.

[1168] The compositions of the disclosure can further include one or more additional pharmaceutical agents such as a chemotherapeutic, steroid, anti-inflammatory compound, or immunosuppressant, examples of which are provided herein.

[1169] Labeled Compounds and Assay Methods

[1170] Another aspect of the present invention relates to fluorescent dye, spin label, heavy metal or radio-labeled compounds of the invention that would be useful not only in imaging but also in assays, both in vitro and in vivo, for localizing and quantitating the STAT6 in tissue samples, including human, and for identifying STAT6 ligands by inhibition binding of a labeled compound. Accordingly, the present invention includes STAT6 biochemical assays that contain such labeled compounds.

[1171] The present invention further includes isotopically -labeled compounds of the invention. An “isotopically” or “radio -labeled” compound is a compound of the invention where one or more atoms are replaced or substituted by an atom having an atomic mass or mass number different from the atomic mass or mass number typically found in nature ( / . e., naturally occurring). Suitable radionuclides that may be incorporated in compounds of the present invention include but are not limited to2H (also written as D for deuterium),3H (also written as T for tritium),11C,13C,14C,13N,15N,15O,17O,18O,18F,35S,36C1,82Br,75Br,76Br,77Br,123I,124I,125I and131I. The radionuclide that is incorporated in the instant radio-labeled compounds will depend on the specific application of that radio -labeled compound. For example, for in vitro STAT6 labeling and competition assays, compounds that incorporate3H,54057-0036W01 / SNV0027-W01 PATENT

[1172] 14C,82Br,125I,131I, or35S will generally be most useful. For radio-imaging applications11C,18F,125I,123I,124I,131I,75Br,76Br or77Br will generally be most useful.

[1173] One or more constituent atoms of the compounds presented herein can be replaced or substituted with isotopes of the atoms in natural or non-natural abundance. In some embodiments, one or more atoms are replaced or substituted by deuterium. For example, one or more hydrogen atoms in a compound of the present disclosure can be replaced by deuterium atoms (e.g., one or more hydrogen atoms of a Ci-6 alkyl group of Formula I can be optionally substituted with deuterium atoms, such as -CDs being substituted for -CHs). In some embodiments, alkyl groups of the disclosed Formulas can be perdeuterated.

[1174] In some embodiments, the compound provided herein, or a pharmaceutically acceptable salt thereof, comprises at least one deuterium atom.

[1175] In some embodiments, the compound provided herein, or a pharmaceutically acceptable salt thereof, comprises two or more deuterium atoms.

[1176] In some embodiments, the compound provided herein, or a pharmaceutically acceptable salt thereof, comprises three or more deuterium atoms.

[1177] In some embodiments, for a compound provided herein, or a pharmaceutically acceptable salt thereof, all of the hydrogen atoms are replaced by deuterium atoms (z.e., the compound is “perdeuterated”).

[1178] It is understood that a “radio-labeled ” or “labeled compound” is a compound that has incorporated at least one radionuclide. In some embodiments the radionuclide is selected from the group consisting of3H,14C,1251,35S and82Br.

[1179] Synthetic methods for including isotopes into organic compounds are known in the art (Deuterium Labeling in Organic Chemistry by Alan F. Thomas (New York, N. Y., Appleton-Century-Crofts, 1971; The Renaissance of H / D Exchange by Jens Atzrodt, Volker Derdau, Thorsten Fey and Jochen Zimmermann, Angew. Chem. Int. Ed. 2007, 7744-7765; The Organic Chemistry of Isotopic Labelling by James R. Hanson, Royal Society of Chemistry, 2011). Isotopically labeled compounds can be used in various studies such as NMR spectroscopy, metabolism experiments, and / or assays.

[1180] Substitution with heavier isotopes, such as deuterium, may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements, and hence may be preferred in some circumstances, (see e.g., A. Kerekes et. al. J. Med. Chem. 2011, 54, 201-210; R. Xu et. al. J. Label Compd.

[1181] Radiopharm. 2015, 58, 308-312). In particular, substitution at one or more metabolism sites may afford one or more of the therapeutic advantages.

[1182] A radio-labeled compound of the invention can be used in a screening assay to identify / evaluate compounds. In general terms, a newly synthesized or identified compound54057-0036W01 / SNV0027-W01 PATENT

[1183] (i.e., test compound) can be evaluated for its ability to reduce binding of the radio-labeled compound of the invention to the STAT6. Accordingly, the ability of a test compound to compete with the radio-labeled compound for binding to the STAT6 directly correlates to its binding affinity.

[1184] Kits

[1185] The present invention also includes pharmaceutical kits useful, for example, in the treatment or prevention of STAT6-associated diseases or disorders referred to herein which include one or more containers containing a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention. Such kits can further include, if desired, one or more of various conventional pharmaceutical kit components, such as, for example, containers with one or more pharmaceutically acceptable carriers, additional containers, etc., as will be readily apparent to those skilled in the art. Instructions, either as inserts or as labels, indicating quantities of the components to be administered, guidelines for administration, and / or guidelines for mixing the components, can also be included in the kit.

[1186] The invention will be described in greater detail by way of specific examples. The following examples are offered for illustrative purposes, and are not intended to limit the invention in any manner. Those of skill in the art will readily recognize a variety of non-critical parameters which can be changed or modified to yield essentially the same results.

[1187] EXAMPLES

[1188] Experimental procedures for compounds of the invention are provided below.

[1189] Preparatory LC-MS purifications of some of the compounds prepared are performed on Waters mass directed fractionation systems. The basic equipment setup, protocols, and control software for the operation of these systems have been described in detail in the literature. See e.g. “Two-Pump At Column Dilution Configuration for Preparative LC-MS”, K. Blom, J. Combi. Chem., 4, 295 (2002); “Optimizing Preparative LC-MS Configurations and Methods for Parallel Synthesis Purification”, K. Blom, R. Sparks, J. Doughty, G. Everlof, T. Haque, A. Combs, J. Combi. Chem., 5, 670 (2003); and " Preparative LC-MS Purification: Improved Compound Specific Method Optimization", K. Blom, B. Glass, R. Sparks, A. Combs, J. Combi. Chem., 6, 874-883 (2004). The compounds separated are typically subjected to analytical liquid chromatography mass spectrometry (LCMS) for purity check.

[1190] Some of the compounds prepared are also separated on a preparative scale by reverse -phase high performance liquid chromatography (RP-HPLC) with MS detector or flash chromatography (silica gel).54057-0036W01 / SNV0027-W01 PATENT

[1191] Intermediate 1. l-(5-(4,4,5,5-Tetramethyl-l,3,2-dioxaborolan-2-yl)-3,6-dihydropyridin-l(2H)-yl)-3-(lH-l,2,3-triazol-l-yl)propan-l-one

[1192]

[1193] To a solution of 3-(lH-l,2,3-triazol-l-yl)propanoic acid (423 mg, 3.00 mmol) in 7.5 mL of pyridine was added 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-l,2,3,6-tetrahydropyridine hydrochloride (737 mg, 3.00 mmol) and l-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI, 633 mg, 3.30 mmol). The reaction mixture was stirred at 25 °C for 3 hours. The mixture was concentrated under reduced pressure. The residue was purified by column chromatography to give the desired product (458 mg, 46% yield) as a stick oil. LC-MS calculated for C16H26BN4O3 (M+H)+m / z = 333.2; found 333.4.

[1194] Intermediate 2.2-(l-(2,6-Dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo [d] imidazol-4-yl)acetaldehyde

[1195]

[1196] Step 1: (E)-3-(4-(2-ethoxyvinyl)-3-methyl-2-oxo-2, 3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione

[1197]

[1198] To a solution of 3-(4-bromo-3-methyl-2-oxo-benzimidazol-l-yl)piperidine-2, 6-dione (507.24 mg, 1.50 mmol), Pd(dppf)Cl2• DCM (122.50 mg, 0.15 mmol), CsF (455.71 mg, 3.00 mmol) in 7.5 mL of dioxane, and 1.5 mL of water was added 2-[(£)-2 -ethoxyvinyl] -4, 4,5,5-54057-0036W01 / SNV0027-W01 PATENT

[1199] tetramethyl-l,3,2-dioxaborolane (0.48 mL, 445.65 mg, 2.25 mmol) under nitrogen atmosphere. The mixture was stirred at 90 °C for 14 hours. The mixture was diluted with 20 mL of water and extracted with ethyl acetate (10 mL x 3). Organic phase was collected, dried over Na2SO4, and concentrated under vacuum. The crude product was purified by column chromatography to give the desired product (415 mg, 84% yield) as a yellow solid. LC-MS calculated for C17H20N3O4 (M+H)+m / z = 330.1; found 330.1.

[1200] Step 2: 2-(l-(2, 6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2, 3-dihydro-lH-benzo[d]imidazol-4-yl)acetaldehyde

[1201] To a solution of (E)-3-(4-(2-ethoxyvinyl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione (415.6 mg, 1.26 mmol) in 2.0 mL THF was added 3N HC1 (4.0 mL). The reaction mixture was stirred at 25 °C for 1 hour and then 40 °C for 2 hours. The mixture was extracted with ethyl acetate 3 times, washed with brine, and dried over ISfeSCL. Filtration and solvent were removed to give the desired product (312 mg, 82% yield) as a brown solid. LC-MS calculated for C15H16N3O4 (M+H)+m / z = 302.1; found 302.0.

[1202] Intermediate 3: 3-(l-(2,6-Dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-5-yl)propanal

[1203]

[1204] Step 1: 3-(5-(2-(l, 3-dioxolan-2-yl)ethyl)-3-methyl-2-oxo-2, 3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione

[1205]

[1206] To a solution of 3-(5-bromo-3-methyl-2-oxo-benzimidazol-l-yl)piperidine-2, 6-dione (507.24 mg, 1.50 mmol), Ni(dtbbpy)CL (17.91 mg, 0.04 mmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6 (33.66 mg, 0.03 mmol) in 30 mL of DME was added 2,6-dimethylpyridine (1.39 mL, 1285.84 mg, 12.00 mmol), bis(trimethylsilyl)silyl-trimethyl-silane (0.56 mL, 447.59 mg, 1.8054057-0036W01 / SNV0027-W01 PATENT

[1207] mmol), and 2-(2-bromoethyl)-l,3-dioxolane (0.23 mL, 353.00 mg, 1.95 mmol). The mixture was degassed with the flow of N2 for 10 minutes. The reaction mixture was irradiated with blue LED lamp (390 nm) and stirred (cooled with a fan) at 25 °C for 14 hours. The mixture was filtered and then concentrated under reduced pressure. The residue was purified by column chromatography to give the desired product (287 mg, 53% yield) as a white solid. LC-MS calculated for C18H22N3O5 (M+H)+m / z = 360.2; found 360.2.

[1208] Step 2: 3-(I-(2, 6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2, 3-dihydro-lH-benzo[d]imidazol-5-yl)propanal

[1209] A solution of 3-(5-(2-(l,3-dioxolan-2-yl)ethyl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione (287.1 mg, 0.8 mmol) in 2.6 mL ofHCOOH was heated at 40 °C for 2 hours. The mixture was concentrated under reduced pressure to give the desired product in quantitative yield as a brown solid. LC-MS calculated for C16H18N3O4(M+H)+m / z = 316.1; found 316.1.

[1210] Intermediate 4: tert- Butyl 4-(l-hydroxy-l,3-dihydrobenzo[c][l,2]oxaborol-5-yl)piperazine-l-carboxylate

[1211]

[1212] To a solution of methyl 3 -bromobenzoate (3.00 g, 13.95 mmol), tert-butyl piperazine- 1-carboxylate HC1 salt (3.73 g, 16.74 mmol) in 70 mL dioxane at room temperature were added sodium tert-butoxide (3.35 g, 34.88 mmol) and RuPhos Pd G4 (2.72 g, 2.79 mmol) in 60 mL toluene. The reaction was degassed and refilled with N2 gas three times. Then the reaction was stirred at 100 °C for 6 hours. Upon cooling to room temperature, the reaction was diluted with water and extracted with DCM (100 mL x 3). The combined organic fractions were washed with brine, dried over anhydrous sodium sulfate, filtered, then concentrated under reduced pressure, then purified by silica gel column chromatography,54057-0036W01 / SNV0027-W01 PATENT

[1213] eluting with EtOAc in hexane (0 to 100% to give the desired product. LC-MS calculated for C17H25N2O4 (M+H)+m / z = 321.2; found 321.1.

[1214]

[1215] To a solution of tert-butyl 4-(3-(methoxycarbonyl)phenyl)piperazine-l-carboxylate (1.30 g, 4.06 mmol) in 40 mb DCM at room temperature was added N-bromosuccinimide (866.6 mg, 4.87 mmol). The resulting solution was stirred at room temperature for one hour, which was then diluted with 50 mb of water and extracted with DCM (20 mb x 3). The combined organic layers were dried over ISfeSCE, filtered, concentrated under reduced pressure, then purified by silica gel column chromatography, eluting with EtOAc in hexane (0 to 50%) to afford the desired product. LC-MS calculated for Ci? H24BrN2O4 (M+H)+m / z = 401.1; found 401.0.

[1216]

[1217] At 0 °C, to a solution of tert-butyl 4-(4-bromo-3-(methoxycarbonyl)phenyl)piperazine-l -carboxylate (1.20 g, 3.01 mmol) in 30 mb DCM was added DIBAL-H (1 M in hexane, 7.51 mb, 7.51 mmol) dropwise. The resulting solution was stirred at the same temperature for one hour, then diluted with 30 mb 0.5 M HC1 solution, and extracted with EtOAc 3 times. The combined organic layers were dried over sodium sulfate, filtered, concentrated under reduced pressure, and then purified by silica gel column chromatography, eluting with EtOAc in DCM (0 to 100%) to afford the desired product. LC-MS calculated for Cid^Br^Os (M+H)+m / z = 371.1; found 371.0.

[1218] Step 4: tert-butyl 4-(l-hydroxy-l,3-dihydrobenzo[c] [l,2]oxaborol-5-yl)piperazine-l-carboxylate

[1219] To a mixture of tert-butyl 4-(4-bromo-3-(hydroxymethyl)phenyl)piperazine-l-carboxylate (100.00 mg, 0.27 mmol) and 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-l,3,2-54057-0036W01 / SNV0027-W01 PATENT

[1220] dioxaborolan-2-yl)-l,3,2-dioxaborolane (75.24 mg, 0.30 mmol) in 3 mb dioxane was added KO Ac (66.1 mg, 0.67 mmol) and Pd(dppf)C12DCM (32.99 mg, 0.04 mmol). The resulting mixture was heated at 100 °C for 2 hours under a nitrogen atmosphere. Upon completion of the reaction, the mixture was cooled to room temperature, and the solvent was removed under reduced pressure. The residue was purified with silica gel chromatography, eluting with EtOAc in DCM (0 to 100%) to give the desired product. LC-MS calculated for C16H24BN2O4 (M+H)+m / z = 319.2; found: 319.1.

[1221] Intermediate 5. tert- Butyl 8-bromo-l,2,4a,5-tetrahydrobenzo[b]pyrazino[l,2-d] [l,4]oxazine-3(4H)-carboxylate

[1222]

[1223] Step 1: tert-butyl 4-(2-fluoro-4-nitrophenyl)-3-(hydroxymethyl)piperazine-l-carboxylate

[1224]

[1225] To a solution of tert-butyl 3 -(hydroxymethyl)piperazine-l -carboxylate (3.24 g, 15.00 mmol) in DMF (20 mb) was added l,2-difhioro-4-nitrobenzene (1.66 mb, 2.39 g, 15.00 mmol) and DIEA (5.23 mL, 3877.29 mg, 30.00 mmol). The mixture was stirred at 120 °C for 16 hours. The mixture was diluted with ethyl acetate (300 mL), washed with H2O, dried over Na2SC>4 and concentrated in vacuo to give the residue. The residue was subjected to column chromatography over silica gel (gradient elution: 0 - 35% EtOAc in hexanes) to give the product as a yellow solid (2.36 g, 44% yield). LC-MS calculated for C16H23FN3O5 (M+H)+m / z = 356.2; found 356.2.

[1226] Step 2: tert-butyl 8-nitro-l,2,4a,5-tetrahydrobenzo [b]pyrazino [1,2-d] [l,4]oxazine-3(4H)-carboxylate

[1227]

[1228] To a solution of tert-butyl 4-(2-fluoro-4-nitrophenyl)-3-(hydroxymethyl)piperazine-l-carboxylate (2.36 g, 6.64 mmol) in DMF (7 mb) was added NaH (398.43 mg, 9.96 mmol) at 0 °C. The mixture was stirred at 80 °C for 3 hours. The mixture was diluted with ethyl acetate (300 mb), washed with brine 3 times, dried over ISfeSCh, and concentrated in vacuo to give54057-0036W01 / SNV0027-W01 PATENT

[1229] the residue. The residue was subjected to column chromatography over silica gel (0 - 35% EtOAc in hexanes) to give the product as a yellow solid (1.28 g, 57% yield). LC-MS calculated for C16H22N3O5 (M+H)+m / z = 336.2; found 336.2.

[1230] Step 3: tert-butyl 8-amino-l,2,4a,5-tetrahydrobenzo[b]pyrazino[l,2-d] [l,4]oxazine-3(4H)~ carboxylate

[1231]

[1232] To a solution of tert-butyl 8-nitro-2,4,4a,5-tetrahydro-lH-pyrazino[2,l-c][l,4]benzoxazine-3-carboxylate (1.27 g, 3.79 mmol) in THF / MeOH = 3.8 mL / 7.6 mb was added Pd / C (10%w / w) (40.30 mg, 0.38 mmol). The mixture was stirred at 25 °C under an atmosphere of H2 for 14 hours. The mixture was filtered and concentrated in vacuo to give the residue. The residue was subjected to column chromatography over silica gel (0 - 67% EtOAc in hexanes) to give the product as a purple solid (1.1 g, 95% yield). LC-MS calculated for C16H24N3O3 (M+H)+m / z = 306.2; found 306.2.

[1233] Step 4: tert-butyl 8-bromo-l,2,4a,5-tetrahydrobenzo[b]pyrazino[l,2-d] [l,4]oxazine-3(4H)-carboxylate

[1234] To a solution of CuBr2 (482.73 mg, 2.16 mmol) in 4.5 mL MeCN was added tertbutyl nitrite (278.48 uL, 241.45 mg, 2.34 mmol) at 0 °C. The mixture was stirred for 10 min, after which time the tert-butyl 8-amino-l,2,4a,5-tetrahydrobenzo[b]pyrazino[l,2-d][l,4]oxazine-3(4H)-carboxylate (550.00 mg, 1.80 mmol) was added in 4.5 mL MeCN at 0 °C. The reaction was stirred at 25 °C for 14 hours. Upon completion, the mixture was filtered and concentrated in vacuo to give the residue. The residue was subjected to column chromatography over silica gel (0 - 10% EtOAc in hexanes) to give the product as white solid (50.3 mg, 8% yield). LC-MS calculated for CieE^Br^Os (M+H)+m / z = 369.1; found 369.1.

[1235] Intermediate 6. tert- Butyl 9-bromo-l,2,4a,5-tetrahydrobenzo[b]pyrazino[l,2-d] [l,4]oxazine-3(4H)-carboxylate

[1236]

[1237] Step 1: tert-butyl 3-((4-bromo-2-fluorophenoxy)methyl)piperazine-l-carboxylate54057-0036W01 / SNV0027-W01 PATENT

[1238]

[1239] To a solution of tert-butyl 3 -(hydroxymethyl)piperazine-l -carboxylate (4.33 g, 20.00 mmol) in DMSO (20 mL) was added 4-bromo-l,2-difluoro-benzene (2.71 mb, 4.63 g, 24.00 mmol) and KOH (2.64 g, 40.00 mmol). The mixture was stirred at 120 °C for 16 hours. The mixture was diluted with ethyl acetate (300 mL), washed with H2O, dried over Na2SO4, and concentrated in vacuo to give the residue. The residue was subjected to column chromatography over silica gel (gradient elution: ethyl acetate (EA) in hexanes 0-100%, then methanol in DCM 10%) to give the product as pale red stick gum (5.0 g, 64% yield). LC-MS calculated for CieftsBrFlShOs (M+H)+m / z = 389.1; found 389.1.

[1240] Step 2: tert-butyl 9-bromo-l,2,4a,5-tetrahydrobenzo[b]pyrazino[l,2-d] [l,4]oxazine-3(4H)~ carboxylate

[1241] To a solution of tert-butyl 3-((4-bromo-2-fluorophenoxy)methyl)piperazine-l-carboxylate (3.98 g, 10.2 mmol) in 20 mb THF was added lithium bis(trimethylsilyl)amide (LHMDS, IM in THF, 10.2 mb) at 0 °C. The mixture was stirred for 2 hours at 60 °C. Upon completion, the mixture was diluted with ethyl acetate (100 mb), washed with H2O, dried over Na2SC>4, and concentrated in vacuo to give the residue. The mixture was filtered and concentrated in vacuo to give the residue. The residue was subjected to column chromatography over silica gel (0 - 8% EtOAc in hexanes) to give the product as white solid (201 mg, 5% yield). LC-MS calculated for Cie^BrlShCE (M+H)+m / z = 369.1; found 369.1.

[1242] Intermediate 7. tert- Butyl 4-(l-hydroxy-3,4-dihydro-lH-benzo[c][l,2]oxaborinin-6-yl)piperazine-l-carboxylate

[1243]

[1244] Step 1: 2-(5-bromo-2-chlorophenyl)ethan-l-ol54057-0036W01 / SNV0027-W01 PATENT

[1245]

[1246] At 0 °C, to a solution of methyl 2-(5-bromo-2-chloro-phenyl)acetate (2.50 g, 9.49 mmol) in 60 mL DCM was added DIBAL-H (IM in THF, 23.72 mL, 23.72 mmol) dropwise. The resulting solution was stirred at the same temperature for one hour, then diluted with 1000 mL 0.5 M HC1 solution, and extracted with EtOAc x 3. The combined organic layers were dried over sodium sulfate, filtered, concentrated under reduced pressure, and then purified by silica gel column chromatography, eluting with EtOAc in DCM (0 to 100%) to afford the desired product. LCMS calculated for CsH BrC IO (M+H)+m / z = 235.0; found 235.1.

[1247] Step 2: tert-butyl 4-(4-chloro-3-(2-hydroxyethyl)phenyl)piperazine-l-ccirboxylcite

[1248]

[1249] To a solution of 2-(5-bromo-2-chloro-phenyl)ethanol (1.10 g, 4.67 mmol) in 24 mL toluene at room temperature was added sodium tert-butoxide (0.90 g, 9.34 mmol), tert-butyl piperazine- 1 -carboxylate (1.30 g, 7.01 mmol), Ruphos (435.91 mg, 0.93 mmol) and Ruphos Pd G4 (0.79 g, 0.93 mmol). The reaction was degassed and refilled with N2 gas three times. Then the reaction was stirred at 100 °C for 6 hours. Upon cooling to room temperature, the reaction was diluted with water and extracted with DCM (100 mL x 3). The combined organic fractions were washed with brine, dried over anhydrous sodium sulfate, filtered, then concentrated under reduced pressure, then purified by silica gel column chromatography, eluting with EtOAc in DCM (0 to 100% to give the desired product. LCMS calculated for CI7H26C1N2O3 (M+H)+m / z = 341.2; found 341.0.

[1250] Step 3: tert-butyl 4-(l-hydroxy-3,4-dihydro-lH-benzo[c] [l,2]oxaborinin-6-yl)piperazine-l-carboxylate

[1251] To a solution of tert-butyl 4-[4-chloro-3-(2-hydroxyethyl)phenyl]piperazine-l-carboxylate (240.00 mg, 0.70 mmol) in 4 mL dioxane was added 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-l,3,2-dioxaborolane (357.61 mg, 1.41 mmol),54057-0036W01 / SNV0027-W01 PATENT

[1252] KO Ac (207.32 mg, 2.11 mmol) and [Pd(allyl)(XPhos)]Cl (69.36 mg, 0.11 mmol). The resulting solution was degassed and refilled with N2, which was then heated at 100 °C under N2 for 2 hours. Upon cooling down to room temperature, the solvent was removed under reduced pressure. The residue was purified with silica gel chromatography, eluting with EtOAc in DCM (0 to 100%) to give the desired product. LC-MS calculated for C17H26BN2O4 (M+H)+m / z = 333.2; found: 333.0.

[1253] Intermediate 8.3-(4-Bromo-3-methyl-lH-indazol-l-yl)piperidine-2, 6-dione

[1254]

[1255] To a solution of 4-bromo-3-methyl-lH-indazole (10 g, 47 mmol) in DMSO (100 mL) and THF (100 mL) was added NaH (60% in mineral oil, 5.7 g, 141 mmol) under nitrogen atmosphere at 0 °C. The mixture was stirred at 0 °C for 30 min, then added 3-bromopiperidine-2, 6-dione (9.5 g, 50 mmol). The mixture was stirred at rt for 12 h then diluted with ethyl acetate. The mixture was acidified with formic acid then extracted with ethyl acetate. Organic phase was collected, dried over Na2SO4, and concentrated under vacuum. The resulting solid was collected via filtration to obtain the desired product as white solid which was used directly in the next step without further purification. LC-MS calculated for Ci3Hi3BrN3O2(M+H)+m / z = 322.0; found 322.1.

[1256] Intermediate 9.3-(5-Bromo-3-methyl-lH-indazol-l-yl)piperidine-2, 6-dione

[1257]

[1258] The title compound was prepared using a similar procedure as described for Intermediate 8, with 5-bromo-3-methyl-lH-indazole replacing 4-bromo-3-methyl-lH-indazole. LC-MS calculated for CisHisBrNsCL (M+H)+m / z = 322.0; found 322.1.54057-0036W01 / SNV0027-W01 PATENT

[1259] Intermediate 10.3-(3-Methyl-2-oxo-5-(4-oxopiperidin-l-yl)-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione

[1260]

[1261] Step 1: 3-(3-methyl-2-oxo-5-(l, 4-dioxa-8-azaspiro[4.5 ]decan-8-yl)-2, 3-dihydro-lH-benzo[d]imidazol-l-yl) piperidine -2, 6-dione

[1262]

[1263] To a solution of 3-(5-bromo-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione (5.0 g, 14.7 mmol), RuphosPd-G4 (1.3 g, 1.48 mmol), Ruphos (690 mg, 1.48 mmol), and CS2CO3 (9.1 g, 28 mmol) in 60 mL of DMF was added l,4-dioxa-8-azaspiro[4.5]decane (2.3 g, 16.3 mmol) under nitrogen atmosphere. The mixture was stirred at 100 °C for 12 h. The mixture was then diluted with ethyl acetate and water, acidified with formic acid, and then extracted with ethyl acetate. Organic phase was discarded, the aqueous layer was extracted with DCM / IPA (3:1) several times. The organic layers were collected, dried over Na2SO4, and concentrated under vacuum. The crude product was purified by column chromatography, eluting with MeOH in DCM (0 to 4%) to give the desired product (1.7 g, 30% yield). LC-MS calculated for C20H25N4O5 (M+H)+m / z = 401.2; found 401.2.

[1264] Step 2: 3-(3-methyl-2-oxo-5-(4-oxopiperidin-l-yl)-2, 3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione

[1265] A mixture of 3-(3-methyl-2-oxo-5-(l,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione (1.7 g, 4.3 mmol) in formic acid (30 mL) was stirred at 80 °C for 5h. The reaction mixture was concentrated under vacuum. The crude product was purified by column chromatography, eluting with MeOH in DCM (0 to54057-0036W01 / SNV0027-W01 PATENT

[1266] 5%) to give the desired product (352 mg, 23% yield). LC-MS calculated for C18H21N4O4 (M+H)+m / z = 357.2; found 357.2.

[1267] Intermediates 11-14.

[1268] The compounds of Intermediates 11-14 listed in Table 2 were prepared using a similar procedure as described for Intermediate 10.

[1269] Table 2.

[1270]

[1271] 54057-0036W01 / SNV0027-W01 PATENT

[1272]

[1273] Intermediate 15.3-(l-Methyl-6-(4-oxopiperidin-l-yl)-lH-indazol-3-yl)piperidine-2,6-dione

[1274]

[1275] Step 1: 3-(2,6-bis(benzyloxy)pyridin-3-yl)-6-bromo-l-methyl-lH-indazole

[1276]

[1277] A mixture of 6-bromo-3-iodo-l-methyl-lH-indazole (1.00 g, 2.97 mol), 2,6-bis(benzyloxy)pyridine-3-boronic acid (1.19 g, 3.56 mol), Pd(dppf)C12 (217.2 mg, 0.30 mmol), and cesium carbonate (2.90 g, 8.90 mmol) in 10: 1 dioxane:water (6.6 mb) was heated at 90 °C for 2 hours under nitrogen atmosphere. After cooling to rt, the resulting mixture was diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over magnesium sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluting with 0-50% EtOAc in Hexane to afford the desired product (1.35 g, 91%). LC-MS calculated for C27H23BrN3O2 (M+H)+m / z = 500.1; found 499.9.

[1278] Step 2: 8-(3-(2, 6-bis(benzyloxy)pyridin-3-yl)-l-methyl-lH-indazol-6-yl)-l, 4-dioxa-8-azaspiro[4.5 ]decane54057-0036W01 / SNV0027-W01 PATENT

[1279]

[1280] A mixture of 3-(2,6-bis(benzyloxy)pyridin-3-yl)-6-bromo-l-methyl-lH-indazole (300.0 mg, 0.60 mol), l,4-dioxa-8-azaspiro[4.5]decane (153.3 pL, 1.20 mmol), cesium carbonate (586.0 mg, 1.80 mmol), RuPhos (56.0 mg, 0.12 mmol) and RuPhos Pd G4 (102.0 mg, 0.12 mmol) in 5 mb DMF was heated at 100 °C for 2 hours under nitrogen atmosphere. After cooling to rt, the resulting mixture was diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over magnesium sodium sulfate and filtered. The fdtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluting with 0-100% EtOAc in Hexane to afford the desired product (284.6 mg, 84%). LC-MS calculated for C34H35N4O4 (M+H)+m / z = 563.3; found 563.1.

[1281] Step 3: 3-(l-methyl-6-(l,4-dioxa-8-azaspiro[4.5]decan-8-yl)-lH-indazol-3-yl)piperidine-2,6-dione

[1282]

[1283] To the solution of 8-(3-(2,6-bis(benzyloxy)pyridin-3-yl)-l-methyl-lH-indazol-6-yl)-l,4-dioxa-8-azaspiro[4.5]decane (284.6 mg, 0.51 mmol) in 5 mb THF and 5 mb EtOAc was add Pd / C (10%wt, 300 mg) and heated at 50 °C for 8 hours under hydrogen atmosphere. After cooling to rt, the resulting mixture was filtered through Celite pad, and the filtrate was concentrated under reduced pressure. The crude product was directly used in the next step54057-0036W01 / SNV0027-W01 PATENT

[1284] without further purification. LC-MS calculated for C20H25N4O4 (M+H) m / z = 385.2; found 385.1.

[1285] Step 4: 3-(l-methyl-6-(4-oxopiperidin-l-yl)-lH-indazol-3-yl)piperidine-2, 6-dione

[1286] The solution of 3-(l-methyl-6-(l,4-dioxa-8-azaspiro[4.5]decan-8-yl)-lH-indazol-3-yl)piperidine-2, 6-dione (284.6 mg, 0.51 mmol) in 5 mL formic acid was stirred at 60 °C for 10 hours. After cooling to rt, the resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluting with 0-10% MeOH in DCM to afford the desired product (167.1 mg, 97%). LC-MS calculated for C18H21N4O3 (M+H)+m / z = 341.2; found 341.0.

[1287] Intermediate 16.3-(l-Methyl-7-(4-oxopiperidin-l-yl)-lH-indazol-3-yl)piperidine-2,6-dione

[1288]

[1289] The title compound was prepared using a similar procedure as described for Intermediate 15, with 7-bromo-3-iodo-l-methyl-lH-indazole replacing 6-bromo-3-iodo-l-methyl-lH-indazole in step 1. The final product was purified using flash column chromatography (MeOH / DCM, 0 to 5%), the desired peak was collected as the desired product. LCMS calculated for C18H21N4O3 (M+H)+m / z = 341.2; found 341.2.

[1290] Intermediate 17.2-(l-(2,6-Dioxopiperidin-3-yl)-3-methyl-lH-indazol-4-yl)acetaldehyde

[1291]

[1292] 54057-0036W01 / SNV0027-W01 PATENT

[1293] The title compound was prepared using a similar procedure as described for Intermediate 2, with 3-(4-bromo-3-methyl-lH-indazol-l-yl)piperidine-2, 6-dione replacing 3-(4-bromo-3 -methyl -2 -oxo-benzimidazol-l-yl)piperidine-2, 6-dione in step 1. The final product was purified using flash column chromatography (MeOH / DCM, 0 to 5%), the desired peak was collected as the desired product. LCMS calculated for C15H16N3O3 (M+H)+m / z = 286.1; found 286.1.

[1294] Intermediate 18.2-(3-(2,6-Dioxopiperidin-3-yl)-l-methyl-lH-indazol-7-yl)acetaldehyde

[1295]

[1296] Step 1: 3-(2, 6-bis(benzyloxy)pyridin-3-yl)-7-bromo-l-methyl-lH-indazole

[1297]

[1298] To a solution of 7-bromo-3-iodo-l -methyl- IH-indazole (10.0 g, 29.7 mmol), Pd(dppf)C12 (2.4 g, 2.9 mmol), CS2CO3 (14.5 g, 44.5 mmol) in 100 mb of dioxane and water (5:1) was added (2,6-bis(benzyloxy)pyridin-3-yl)boronic acid (11.9 g, 35.6 mmol) under nitrogen atmosphere. The mixture was stirred at 100 °C for 4 h then diluted with ethyl acetate and water, the mixture was extracted with ethyl acetate. Organic phase was collected, dried over Na2SO4, and concentrated under vacuum. The crude product was purified by column chromatography, eluting with ethyl acetate in hexanes (0 to 30%) to give the desired product as a white solid (8.9 g, 60% yield). LC-MS calculated for C2? H23BrN3O2 (M+H)+m / z = 500.1; found 500.1.

[1299] Step 2: 7-((l, 3-dioxolan-2-yl)methyl)-3-(2, 6-bis(benzyloxy)pyridin-3-yl)-l-methyl-lH-indazole54057-0036W01 / SNV0027-W01 PATENT

[1300]

[1301] To a solution of 3-(2,6-bis(benzyloxy)pyridin-3-yl)-7-bromo-l-methyl-lH-indazole (0.5 g, 1 mmol), Ni(dtbbpy)C12 (12 mg, 0.0.3 mmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6 (22 mg, 0.02 mmol) in 30 mb of DME was added 2,6-dimethylpyridine (856 mg, 8

[1302] mmol), bis(trimethylsilyl)silyl-trimethyl-silane (317 mg, 1.2 mmol), and 2-(bromomethyl)-1,3-dioxolane (200 mg, 1.2 mmol). The mixture was degassed with the flow of N2 for 10 minutes. The reaction mixture was irradiated with blue LED lamp (390 nm) and stirred (cooled with a fan) at 25 °C for 14 hours. The mixture was filtered and then concentrated under reduced pressure. The residue was purified by column chromatography to give the desired product (200 mg, 40% yield) as a white solid. LC-MS calculated for C31H30N3O4 (M+H)+m / z = 508.2; found 508.2.

[1303] Step 3: 3-(7-((l,3-dioxolan-2-yl)methyl)-l-methyl-lH-indazol-3-yl)piperidine-2, 6-dione

[1304]

[1305] A solution 7-(( 1,3 -dioxolan-2-yl)methyl)-3 -(2,6-bis(benzyloxy)pyridin-3 -yl)- 1 -methyl- IH-indazole (200 mg, 0.4 mmol) in EtOH was added Pd / C (10% wt, 200 mg) under nitrogen. The reaction vial was purged with H2 and the reaction mixture was stirred at 50 °C under H2 atmosphere for 12h. The mixture was filtrated and concentrated under reduced pressure to give the desired product a white solid. LC-MS calculated for C17H20N3O4 (M+H)+m / z = 330.1; found 330.1.

[1306] Step 4: 2-(3-(2, 6-dioxopiperidin-3-yl)-l-methyl-lH-indazol-7-yl)acetaldehyde54057-0036W01 / SNV0027-W01 PATENT

[1307] A solution of 3-(7-((l,3-dioxolan-2-yl)methyl)-l-methyl-lH-indazol-3-yl)piperidine-2, 6-dione (100 mg, 0.3 mmol) in 2 mL of HCOOH was heated at 40 °C for 2 hours. The mixture was concentrated under reduced pressure to give the desired product in quantitative yield as a brown solid. LC-MS calculated for C15H16N3O3 (M+H)+m / z = 286.1; found 286.1.

[1308] Intermediate 19. 2-(4-(2,6-Dioxopiperidin-3-yl)-2-fluorophenyl)acetaldehyde

[1309]

[1310] Step 1: 3-(4-((l,3-dioxolan-2-yl)methyl)-3-fluorophenyl)piperidine-2, 6-dione

[1311]

[1312] To a solution of 3-(4-bromo-3-fluoro-phenyl)piperidine-2, 6-dione (143.05 mg, 0.50 mmol), Ni(dtbbpy)C12 (5.97 mg, 0.01 mmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6 (11.22 mg, 0.01 mmol) in 10 mL of DME was added 2,6-dimethylpyridine (0.46 mL, 428 mg, 4.00 mmol), bis(trimethylsilyl)silyl-trimethyl-silane (0.19 mL, 149 mg, 0.6 mmol), and 2-(bromomethyl)- 1,3 -dioxolane (0.08 mL, 125 mg, 0.75 mmol). The mixture was degassed with the flow of N2 for 10 minutes. The reaction mixture was irradiated with blue LED lamp (390 nm) and stirred at 25 °C for 14 hours. The mixture was filtered and then concentrated under reduced pressure. The residue was purified by column chromatography to give the desired product (98.3 mg, 67% yield) as a white solid. LC-MS calculated for C15H17FNO4 (M+H)+m / z = 294.1; found 294.0.

[1313] Step 2: 2-(4-(2, 6-dioxopiperidin-3-yl)-2-fluorophenyl)acetaldehyde

[1314] A solution of 3-(4-((l,3-dioxolan-2-yl)methyl)-3-fluorophenyl)piperidine-2, 6-dione (98.3 mg, 0.34 mmol) in 1.0 mL of HCOOH was heated at 50 °C for 1 hour. The mixture was concentrated under reduced pressure, the crude was titrated with DCM / Et2O / Hexanes to give the desired product as a yellow solid (70.9 mg, 85%). LC-MS calculated for C13H13FNO3 (M+H)+m / z = 250.1; found 250.1.

[1315] Intermediate 20. 3-(3-Fluoro-4-(4-oxopiperidin-l-yl)phenyl)piperidine-2, 6-dione54057-0036W01 / SNV0027-W01 PATENT

[1316]

[1317] Step 1: ethyl 2-(3-fluoro-4-(l,4-dioxa-8-azaspiro[4.5]decan-8-yl)phenyl)acetate

[1318]

[1319] To a solution of RuPhos Pd G4 (850.39 mg, 1.00 mmol), RuPhos (466.63 mg, 1.00 mmol), CS2CO3 (4072.75 mg, 12.50 mmol) in dioxane (50 mL) was added ethyl 2-(4-bromo-3-fluoro-phenyl)acetate (888.05 pL, 1305.44 mg, 5.00 mmol) and l,4-dioxa-8-azaspiro[4.5]decane (0.97 pL, 1073.88 mg, 7.50 mmol). The mixture was degassed for 5 min and kept at 100 °C for 14 h. The mixture was filtered and then concentrated under reduced pressure. The residue was purified by column chromatography (EA in hexanes 0-10%) to give the desired product (775 mg, 48% yield). LC-MS calculated for C17H23FNO4 (M+H)+m / z = 324.2; found 324.2.

[1320] Step 2: 3-(3-fluoro-4-(l,4-dioxa-8-azaspiro[4.5]decan-8-yl)phenyl)piperidine-2, 6-dione

[1321]

[1322] To a solution of prop-2 -enamide (170.35 mg, 2.40 mmol) and ethyl 2-[4-(l,4-dioxa-8-azaspiro[4.5]decan-8-yl)-3-fluoro-phenyl]acetate (775.00 mg, 2.40 mmol) in THF (9.6 mL) was added / B11OK (2.4 mL, 2.40 mmol) at 0 °C. The mixture was then warmed to 50 °C and kept for 2 hours. The mixture was filtered and then concentrated under reduced pressure. The residue was purified by column chromatography (ethyl acetate (EA) in hexanes 0-70%) to give the desired product (114 mg, 14% yield). LC-MS calculated for C18H22FN2O4 (M+H)+m / z = 349.2; found 349.2.

[1323] Step 3: 3-(3-fluoro-4-(4-oxopiperidin-l-yl)phenyl)piperidine-2, 6-dione

[1324] A solution of 3-(3-fluoro-4-(l,4-dioxa-8-azaspiro[4.5]decan-8-yl)phenyl)piperidine-2, 6-dione (114 mg, 0.33 mmol) in 1.0 mL of HCOOH was heated at 40 °C for 2 hours. The54057-0036W01 / SNV0027-W01 PATENT

[1325] mixture was concentrated under reduced pressure, the crude was purified by column chromatography (EA in hexanes 0-75%) to give the desired product (63 mg, 63% yield). LC-MS calculated for C16H18FN2O3 (M+H)+m / z = 305.1; found 305.1.

[1326] Intermediate 21. tert-Butyl 5-bromo-6-fluoro-3H-spiro[isobenzofuran-l,4'-piperidine]-1 '-carboxylate

[1327] Boc

[1328]

[1329] Step 1: (5-bromo-4-fluoro-2-iodophenyl)methanol

[1330]

[1331] A solution of methyl 5 -bromo-4-fluoro-2 -iodobenzoate (5.0 g, 13.9 mmol) in Et2O (100 mL) was added LiBFL (2M in THF, 27.9 mmol) and MeOH (2 mL) under nitrogen at 0 °C. The reaction mixture was stirred at 0 °C under H2 atmosphere for Ih. The resulting mixture was diluted with EA, and the mixture was washed sequentially with water and saturated brine, and dried over anhydrous Na2SC>4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to afford the desired product as a white solid.

[1332] Step 2: tert-butyl 4-(4-bromo-5-fluoro-2-(hydroxymethyl)phenyl)-4-hydroxypiperidine-l-carboxylate

[1333]

[1334] To a dried round bottom flask, charged with a magnetic stir bar and (5-bromo-4-fluoro-2-iodophenyl)methanol (3.0 g, 9.1 mmol) was added anhydrous DCM, the flask was cooled to -78 °C. Then, nBuLi (2.5 M solution in hexanes, 2.2 eq.) was added slowly. After the mixture was maintained at -78 °C for 1 h, a solution of tert-butyl 4-oxopiperidine-l-carboxylate (2.5 g, 12 mmol) in anhydrous DCM was added dropwise. The mixture was warmed gradually to rt and allowed to stir for lOmin. The mixture was quenched with saturated NH4CI (aq.) and the aqueous layer was separated and extracted with EA. The organic layers were combined, dried over anhydrous Na2SC>4, filtered and concentrated. The54057-0036W01 / SNV0027-W01 PATENT

[1335] crude material was purified via column chromatography on silica gel (0-45% EA in hexanes) to give the desired product (1.1 g, 30%). LC-MS calculated for Cnf^BrFNCE (M+H)+m / z = 404.1; found 404.1.

[1336] Step 3: tert-butyl 5-bromo-6-fluoro-3H-spiro [isobenzofuran- 1,4'-piperidine]-l'-carboxylate To a solution of tert-butyl 4-(4-bromo-5-fluoro-2-(hydroxymethyl)phenyl)-4-hydroxypiperidine-1 -carboxylate (1.1 g, 2.7 mmol) in DCM (20 m ) added EtsN (0.43 g, 4.2 mmol). The mixture was cooled to 0 °C and methanesulfonyl chloride (0.4 g, 3.5 mmol) was added dropwise. The mixture was warmed to rt overnight. The mixture was diluted with DCM, washed with NaHCOs (aq.), NaCl (aq.). The organic layers were combined, dried over anhydrous ISfeSCE, filtered and concentrated. The crude material was purified via column chromatography on silica gel (0-15% EA in hexanes) to give the desired product (830 mg, 80% yield) as a colorless oil. LC-MS calculated for C’n^BrFNCf (M+H)+m / z = 386.1; found 386.1.

[1337] Intermediate 22. tert-Butyl 5-chloro-3H-spiro[isobenzofuran-l,4'-piperidine]-l'-carboxylate

[1338] Boc

[1339]

[1340] The title compound was prepared using a similar procedure as described for Intermediate 21, with (2-bromo-5-chlorophenyl)methanol replacing (5-bromo-4-fluoro-2-iodophenyl)methanol in step 2. LC-MS calculated for C17H23CINO3 (M+H)+m / z = 324.1; found 324.1.

[1341] Intermediate 23. tert-Butyl 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-3H-spiro[isobenzofuran-l,4'-piperidine]-l'-carboxylate

[1342] Boc

[1343]

[1344] 54057-0036W01 / SNV0027-W01 PATENT

[1345] A solution of tert-butyl 6-chlorospiro[ lH-isobenzofuran-3,4'-piperidine]-T-carboxylate (1271 mg, 3.93 mmol), EhPim (1993.46 mg, 7.85 mmol), KOAc (1156 mg, 11.78 mmol) and [Pd(allyl)(XPhos)]Cl (257 mg, 0.39 mmol) in dioxane (20 mb) was purged with N2. The mixture was then stirred at 100 °C for 1 hour. The mixture was filtered and then concentrated under reduced pressure. The residue was purified by column chromatography (EA in hexanes 0-20%) to give the desired product (1280 mg, 78% yield). LC-MS calculated for C23H35BNO5 (M+H)+m / z = 416.3; found 416.3.

[1346] Intermediate 24. tert-Butyl l-methyl-2-oxo-6-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)spiro [indoline-3, 4'-piperidine] -1 '-carboxylate

[1347]

[1348] Step 1: tert-butyl 6-bromo-l-methyl-2-oxospiro [indoline-3, 4'-piperidine]-l '-carboxylate

[1349]

[1350] To a solution of tert-butyl 6-bromo-2 -oxospiro [indoline-3,4'-piperidine]-T-carboxylate (500.00 mg, 1.31 mmol) in DMF (6.6 m was added NaH (104.90 mg, 2.62 mmol) at 0° C. The resulting suspension was allowed to stir for 30 min before the addition of iodomethane (122.46 pL, 279.21 mg, 1.97 mmol). The reaction was then allowed to stir at rt for 1 hour. The crude was diluted by EtOAc, washed with water and brine. The organic layers were dried overlSfeSCE and concentrated. The residue was used directly for the next step. LC-MS calculated for CisE^BrlShCh (M+H)+m / z = 395.1; found 395.1.

[1351] Step 2: tert-butyl l-methyl-2-oxo-6-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl) spiro [indoline- 3, 4 '-piperidine ]-l '-carboxylate54057-0036W01 / SNV0027-W01 PATENT

[1352]

[1353] A solution of tert-butyl 6-bromo-l-methyl-2-oxospiro[indoline-3,4'-piperidine]-r-carboxylate (150.00 mg, 0.32 mmol), EhPim (161.89 mg, 0.64 mmol), KOAc (93.85 mg, 0.96 mmol) and Pd(dppf)C12 • DCM (52.06 mg, 0.06 mmol) in dioxane (1 mb) was purged with N2. The mixture was then stirred at 90 °C for 2 hours. On completion, the solvent was removed under reduced pressure and the residue was purified by FCC (0-20% EA / hexanes) to give desired product. LC-MS calculated for C24H36BN2O5 (M+H)+m / z = 443.3; found 443.3.

[1354] Intermediate 25. tert-Butyl l-methyl-6-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)spiro [indoline-3, 4'-piperidine] -1 '-carboxylate

[1355] Boc

[1356]

[1357] Step 1: tert-butyl 6-bromo-l -methylspiro [indoline- 3,4'-piperidine]-l '-carboxylate

[1358]

[1359] To a solution of tert-butyl 6-bromo-l-methyl-2-oxospiro[indoline-3,4'-piperidine]-T-carboxylate (417.70 mg, 0.89 mmol) in THF (8.9 m ) was added BH3-DMS, 0 °C, 18 hours. The mixture was slowly quenched via the addition of MeOH, stirred for another 30 min. The mixture was concentrated. The residue was purified by silica gel column chromatography, eluting with EtOAc in hexanes (0 to 20%) to provide the desired product (287 mg, 88% yield). LC-MS calculated for CisFFeBrNhCE (M+H)+m / z = 381.1; found 381.1.54057-0036W01 / SNV0027-W01 PATENT

[1360] Step 2: tert-butyl l-methyl-6-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)spiro[indoline- 3, 4 '-piperidine ]-l '-carboxylate

[1361] A solution of tert-butyl 6-bromo-l-methylspiro[indoline-3,4'-piperidine]-l'-carboxylate (143 mg, 0.38 mmol), EhPim (190.45 mg, 0.75 mmol), KOAc (110.41 mg, 1.12 mmol) and Pd(dppf)C12 • DCM (61.25 mg, 0.07 mmol) in dioxane (1 mb) was purged with N2. The mixture was then stirred at 90 °C for 2 hours. On completion, the solvent was removed under reduced pressure and the residue was purified by FCC (0-20% EA / hexanes) to give desired product. LC-MS calculated for C24H38BN2O4 (M+H)+m / z = 429.3; found 429.3.

[1362] Intermediate 26. tert-Butyl 3-oxo-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-3H-spiro[isobenzofuran-l,4'-piperidine]-l'-carboxylate

[1363]

[1364] Step 1: tert-butyl 5-bromo-3-oxo-3H-spiro [isobenzofuran- l,4'-piperidine]-l '-carboxylate

[1365]

[1366] To a solution of methyl 5 -bromo-2 -iodo-benzoate (6.67 g, 19.56 mmol) in THF (100 m ) and tert-butyl 4-oxopiperidine-l -carboxylate (4.29 g, 21.52 mmol) was added isopropylmagnesium chloride -lithium chloride complex (16.55 m, 21.52 mmol) at -78 °C, and react at -78°C for 2 hours. After the reaction is completed, add water (5 mb) at 0°C to quench the reaction. Then extract with ethyl acetate (3 x 40 mb), wash the combined organic layer with water (3 x 20 mb), and dry with anhydrous sodium sulfate. After filtration, the filtrate is concentrated under reduced pressure, and the residue is purified by silica gel column chromatography 0-25% EtOAc in hexanes to give desire product (2.4 g, 32% yield). EC-MS calculated for CnbhiBrNCh (M+H)+m / z = 382.1; found 382.1.

[1367] Step 2: tert-butyl 3-oxo-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-3H-spiro[isobenzofuran-l, 4 '-piperidine ]-l '-carboxylate54057-0036W01 / SNV0027-W01 PATENT

[1368] A solution of tert-butyl 5 -bromo-3-oxo-3H-spiro [isobenzofuran- l,4'-piperidine]-T-carboxylate (45.9 mg, 0.12 mmol), B2pin2 (45.7 mg, 0.18 mmol), KOAc (98.2 mg, 0.36 mmol) and Pd(dppf)C12 • DCM (19.6 mg, 0.02 mmol) in dioxane (1 mL) was purged with N2. The mixture was then stirred at 90 °C for 2 hours. On completion, the solvent was removed under reduced pressure and the residue was purified by FCC (0-20% EA / hexanes) to give desired product. LC-MS calculated for C23H33BNO6 (M+H)+m / z = 430.2; found 430.2.

[1369] Intermediate 27. tert-Butyl 2-methyl-3-oxo-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)spiro[isoindoline-l,4'-piperidine]-l'-carboxylate

[1370]

[1371] A solution of tert-butyl 4-oxopiperidine-l -carboxylate (6.38 g, 32.01 mmol) and (4-methoxyphenyl)methanamine (4.39 mL, 4.61 g, 33.61 mmol) in toluene (70 mL) was refluxed for 14 hours. The mixture was concentrated under reduced pressure and used directly in the next step.

[1372] Step 2: tert-butyl 4-(5-chloro-2-iodo-N-(4-methoxybenzyl)benzamido)-3,6-dihydropyridine-1 ( 2H)-carboxylate

[1373]

[1374] A solution of 5-chloro-2-iodo-benzoic acid (7.17 g, 25.38 mmol) was heated in SOCI2 (80 mL) at 80 °C for 5 hours. The mixture was concentrated under reduced pressure. To the residue was added the product from step 1 and EtsN (10.61 mL, 7.70 g, 76.14 mmol) and54057-0036W01 / SNV0027-W01 PATENT

[1375] toluene (80 mb). The mixture was reflux at 120 °C for 18 hours. Once complete, the mixture was diluted with water, extracted with EtOAc three times, washed with NaCl (aq.), dried over Na2SO4. The mixture was filtered and then concentrated under reduced pressure. The residue was purified by column chromatography (EA in hexanes 0-25%) to give the desired product (13.6 g, 92% yield). LC-MS calculated for C25H29CIIN2O4 (M+H)+m / z = 583.1; found 583.1.

[1376] Step 3: tert-butyl 5-chloro-2-(4-methoxybenzyl)-3-oxo-2',3'-dihydro-l 'H-spiro[isoindoline-l,4'-pyridine]-l '-carboxylate

[1377] Boc

[1378]

[1379] To a solution of tert-butyl 4-[(5-chloro-2-iodo-benzoyl)-[(4-methoxyphenyl)methyl]amino]-3,6-dihydro-2H-pyridine- 1 -carboxylate (13.05 g, 22.39 mmol) in MeCN (120 mb) was added Pd(OAc)2 (502.67 mg, 2.24 mmol), triphenylphosphane (1174.50 mg, 4.48 mmol), K2CO3 ( 6188.75 mg, 44.78 mmol) and tetrabutylammonium bromide (7217.70 mg, 22.39 mmol). The mixture was degassed with the flow N2 for 10 min and heated at 90 °C for 4 hours. The mixture was filtered and then concentrated under reduced pressure. The residue was purified by column chromatography (EA in hexanes 0-25%) to give the desired product (7.8 g, 76% yield). LC-MS calculated for C25H28C1N2O4 (M+H)+m / z = 455.2; found 455.2.

[1380] Step 4: 5-chloro-2',3'-dihydro-l 'H-spiro[isoindoline-l,4'-pyridin]-3-one

[1381]

[1382] To a solution of tert-butyl 5-chloro-2-(4-methoxybenzyl)-3-oxo-2',3'-dihydro-l'H-spiro[isoindoline-l,4'-pyridine]-T-carboxylate (7.17 g, 15.76 mmol) in TFA / TfOH (20 mL:6.6 mb) was heated at 70 °C for 3 hours. Partial solvent was removed, and the residue was diluted with EtOAc, quenched with 20% NaOH, extracted with EA 3 times, dried over Na2SC>4. The mixture was filtered and then concentrated under reduced pressure and used54057-0036W01 / SNV0027-W01 PATENT

[1383] directly for the next step. LC-MS calculated for C12H12CIN2O (M+H)+m / z = 235.1; found 235.1.

[1384] Step 5: 5-chlorospiro[isoindoline-l,4'-piperidin]-3-one

[1385]

[1386] To a solution of 5 -chloro-2', 3 '-dihydro- 1'H-spiro [isoindoline- l,4'-pyridin] -3 -one (3698.58 mg, 15.76 mmol) in MeOH (100 mL) was added Pt20 (715.75 mg, 3.15 mmol). The mixture was degassed with H2 for 10 min, under H2 flow for 8 hours and then under H2 atmosphere for 14 hours. Then additional Pt20 (357.87 mg, 1.58 mmol) was added, then mixture was stirred under H2 atmosphere for 24 hours. The mixture was filtered and then concentrated under reduced pressure. The residue was purified by column chromatography (MeOH in DCM 0-20%) to give the desired product (2.5 g, 67% yield). LC-MS calculated for C12H14CIN2O (M+H)+m / z = 237.1; found 237.1.

[1387] Step 6: tert-butyl 5-chloro-3-oxospiro [isoindoline-1, 4'-piperidine]-l '-carboxylate

[1388]

[1389] To a solution of 5-chlorospiro[isoindoline-l,4'-piperidin]-3-one (764.00 mg, 3.23 mmol) in THF / water (15 mL / 7.5 mL) was added BOC2O (774.89 mg, 3.55 mmol) and K2CO3 (1338.28 mg, 9.68 mmol). The reaction mixture was stirred at rt for 1 hour. The mixture was diluted with EtOAc, extracted with EtOAc 3 times, dried over Na2SO4. The residue was purified by column chromatography (EtOAc in hexanes 0-50%) to give the desired product (93 mg, 9% yield). LC-MS calculated for C17H22CIN2O3 (M+H)+m / z = 337.1; found 337.1.

[1390] Step 7: tert-butyl 5-chloro-2-methyl-3-oxospiro[isoindoline-l,4'-piperidine]-l '-carboxylate54057-0036W01 / SNV0027-W01 PATENT

[1391] Boc

[1392]

[1393] To a solution of tert-butyl 5 -chloro-3 -oxospiro [isoindoline- l,4'-piperidine]-T-carboxylate (28 mg, 0.08 mmol) in DMF (0.4 mb) at 0° C was added NaH (7 mg, 0.17 mmol). The resulting dark suspension was allowed to stir for 30 min before the addition of iodomethane (8 uL, 18 mg, 0.12 mmol). The reaction was then allowed to stir at rt for Ih. The crude was diluted by EtOAc, washed with water and brine. The organic layers were dried over Na2SC>4 and concentrated. The residue was purified by column chromatography (EtOAc in hexanes 0-40%) to give the desired product (18.5 mg, 64% yield). LC-MS calculated for CI8H24C1N2O3 (M+H)+m / z = 351.1; found 351.1.

[1394] Step 8: tert-butyl 2-methyl-3-oxo-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)spiro[isoindoline-l, 4 '-piperidine ]-l '-carboxylate

[1395] A solution of tert-butyl 5-chloro-2-methyl-3-oxospiro[isoindoline-l,4'-piperidine]-r-carboxylate (19 mg, 52.7 umol), B2Pin2(27 mg, 0.11 mmol), KOAc (16 mg, 0.16 mmol) and XPhos (allyl)PdCl (3 mg, 0.01 mmol) in dioxane (0.25 mb) was purged with N2. The mixture was then stirred at 100 °C for 1 hour. The mixture was filtered and then concentrated under reduced pressure. The residue was purified by column chromatography (EA in hexanes 0-35%) to give the desired product (17 mg, 72% yield). LC-MS calculated for C%H3. BN20 (M+H)+m / z = 443.3; found 443.3.

[1396] Intermediate 28. tert-Butyl 5-chloro-2-methylspiro[isoindoline-l,4'-piperidine]-l'-carboxylate

[1397]

[1398] To a solution of tert-butyl 5 -chloro-2-methyl-3 -oxospiro [isoindoline- l,4'-piperidine] - l'-carboxylate (98 mg, 0.28 mmol) in THF (1.5 mb) was added BH3-DMS (159 uL, 128 mg, 1.68 mmol) at 600C and kept for 18 hours. The mixture was slowly quenched via the addition of MeOH, stirred for another 30 min. The mixture was concentrated. The residue was purified by silica gel column chromatography, eluting with EtOAc in hexanes (0 to 30%) to54057-0036W01 / SNV0027-W01 PATENT

[1399] provide the desired product (61 mg, 65% yield). LC-MS calculated for C18H26CIN2O2 (M+H)+m / z = 337.2; found 337.2.

[1400] Intermediate 29. tert-Butyl 5-chloro-3,3-dimethyl-2-(methylimino)-2,3-dihydro-216-spiro[benzo[c]thiophene-l,4'-piperidine]-l'-carboxylate 2-oxide

[1401]

[1402] Step 1: (2-bromo-5-chlorobenzyl)(tert-butyl)sulfane

[1403]

[1404] A solution of NaOH (2.20 g, 55.00 mmol) in H2O (2.2 mL) was added MeOH (50 mL) and 2-methylpropane-2-thiol (5.81 mL, 4.64 g, 51.50 mmol). Then l-bromo-2-(bromomethyl)-4-chloro-benzene (14.22 g, 50.00 mmol) in 12.5 mL MeOH was added, the mixture was stirred at rt for 14 hours. Then EtOAc and water were added. The mixture was extracted with EtOAc, washed with 0.2 N NaOH, H2O, dry over Na2SO4. The mixture was filtered and then concentrated under reduced pressure. The residue was used directly for the next step. LC-MS calculated for CnHisBrClS (M+H)+m / z = 293.0; found 293.0.

[1405] Step 2: tert-butyl 4-(2-((tert-butylthio)methyl)-4-chlorophenyl)-4-hydroxypiperidine-l-carboxylate

[1406]

[1407] To a dried round bottom flask, charged with a magnetic stir bar and the l-bromo-2-(tert-butylsulfanylmethyl)-4-chloro-benzene (6.90 g, 23.50 mmol) was added anhydrous THF (0.5 M), the flask was cooled to -78 °C. Then, nBuLi (2.5 M solution in hexanes, 2.4 eq.) was added slowly. After the mixture was maintained at -78 °C for 1 h, a solution of tert-butyl 4-oxopiperidine-1 -carboxylate (5.15 g, 25.85 mmol) in anhydrous THF (2.0 M) was added54057-0036W01 / SNV0027-W01 PATENT

[1408] dropwise. The mixture was warmed gradually to rt and allowed to stir overnight. The mixture was quenched with saturated NH4CI (aq.) and the aqueous layer was separated and extracted with EA. The organic layers were combined, dried over anhydrous ISfeSCE, filtered and concentrated. The crude material was purified via column chromatography on silica gel (0- 15% EA in hexanes) to afford the corresponding product (2.34g, 24% yield). LC-MS calculated for C21H33CINO3S (M+H)+m / z = 414.2; found 414.2.

[1409] Step 3: 5-chloro-3H-spiro [benzo [c]thiophene-l,4'-piperidine]

[1410]

[1411] To a solution of tert-butyl 4-(2-((tert-butylthio)methyl)-4-chlorophenyl)-4-hydroxypiperidine-1 -carboxylate (2.34 g, 5.65 mmol) in 48% HBr (4 mb) was added acetic acid (6.0 ml). The mixture was refluxed at 130 °C for 24 hours. Once completed, 20% NaOH was added to adjust pH > 10, extract with EtOAc, dried over anhydrous Na2SO4, filtered and concentrated. The residue was used directly for the next step. LC-MS calculated for C12H15CINS (M+H)+m / z = 240.1; found 240.1.

[1412] Step 4: tert-butyl 5-chloro-3H-spiro[benzo[c]thiophene-l,4’-piperidine]-l ’-carboxylate

[1413]

[1414] To a solution of 5-chloro-3H-spiro[benzo[c]thiophene-l,4’-piperidine] in DCM (30 mb) was added BOC2O (3700 mg, 16.96 mmol) and EtsN (1.18 mb, 0.86 g, 8.48 mmol). The mixture was kept at rt for 1 hour. The mixture was concentrated under reduced pressure. The residue was purified by column chromatography (EtOAc in hexanes 0-5%) to give the desired product (241 mg, 12.5% yield). LC-MS calculated for C17H23CINO2S (M+H)+m / z = 340.1; found 340.1.

[1415] Step 5: tert-butyl 5-chloro-2-imino-2,3-dihydro-2 \6-spiro[benzo[c]thiophene-l,4'-piperidine]-! '-carboxylate 2-oxide54057-0036W01 / SNV0027-W01 PATENT

[1416] Boc

[1417]

[1418] To a solution of tert-butyl 5-chloro-3H-spiro[benzo[c]thiophene-l,4'-piperidine]-T-carboxylate (212.8 mg, 0.63 mmol) in MeOH (0.5 M) was added ammonium carbamate (97.76 mg, 1.25 mmol) and PhI(OAc)2 (504.16 mg, 1.57 mmol). The mixture was kept at rt for 3 hours. The mixture was diluted with EtOAc, extracted with EtOAc 3 times, dried over Na2SO4. The residue was purified by column chromatography (EtOAc in hexanes 0-80%) to give the desired product (125.4 mg, 54% yield). LC-MS calculated for C17H24CIN2O3S (M+H)+m / z = 371.1; found 371.1.

[1419] Step 6: tert-butyl 5-chloro-3,3-dimethyl-2-(methylimino)-2,3-dihydro-2)[-spiro [benzo [c]thiophene-l,4'-piperidine]-l'-carboxylate 2-oxide

[1420] Boc

[1421]

[1422] To a solution of tert-butyl 5-chloro-2-imino-2,3-dihydro-2X6-spiro[benzo[c]thiophene-l,4'-piperidine]-T-carboxylate 2-oxide (116.00 mg, 0.31 mmol) in DMF (1.5 mL) at 0° C was added NaH (25.02 mg, 0.63 mmol). The resulting suspension was allowed to stir for 30 min before the addition of iodomethane (29.21 uL, 66.59 mg, 0.47 mmol). The reaction was then allowed to stir at rt for 14 hours. The crude was diluted by EtOAc, washed with water and brine. The organic layers were dried over Na2SC>4 and concentrated. The residue was purified by column chromatography (EtOAc in hexanes 0-60%) to give the desired product (47 mg, 36% yield). LC-MS calculated for C20H30CIN2O3S (M+H)+m / z = 413.2; found 413.2.

[1423] Intermediate 30. Methyl 6-bromo-4-chloro-7-fluoro-lH-indole-2-carboxylate

[1424]

[1425] 54057-0036W01 / SNV0027-W01 PATENT

[1426] The title compound was prepared using a similar procedure as described for Example 22, with 4-bromo-2-chloro-5-fluorobenzaldehyde replacing 4-bromo-2 -chloro-benzaldehyde in step 1.

[1427] Intermediate 31. Methyl 4-bromo-6-chloro-7-fluoro-lH-indole-2-carboxylate

[1428]

[1429] The title compound was prepared using a similar procedure as described for Example 22, with 2-bromo-4-chloro-5-fluorobenzaldehyde replacing 4-bromo-2 -chloro-benzaldehyde in step 1.

[1430] Intermediate 32. tert-Butyl 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-2,3-dihydrospiro[indene-l,4'-piperidine]-l'-carboxylate

[1431]

[1432] The title compound was prepared using a similar procedure as described for Intermediate 23, with tert-butyl 5-bromo-2,3-dihydrospiro[indene-l,4'-piperidine]-T-carboxylate replacing tert-butyl 5-chloro-3H-spiro[isobenzofuran-l,4'-piperidine]-T-carboxylate.

[1433] Intermediate 33. N-Methyl-5-((methylamino)methyl)picolinamide

[1434]

[1435] Step 1: methyl 5-(((tert-butoxycarbonyl)amino)methyl)picolinate

[1436]

[1437] 54057-0036W01 / SNV0027-W01 PATENT

[1438] A mixture of methyl 5-(aminomethyl)picolinate (0.50 g, 3.0 mmol) (HC1 salt) and BOC2O (0.79 g, 3.6 mmol) in ethanol (10 mL) was added triethylamine (1.26 mL, 9.0 mmol) and then stirred at rt for 1 h. The solvent was removed and then purified by silica gel column chromatography, eluting with EtOAc in hexanes (0 to 100%) to afford the desired product. LCMS calculated for C13H19N2O4 (M+H)+m / z = 267.1; found (M+H)+m / z = 267.1.

[1439] Step 2: methyl 5-(((tert-butoxycarbonyl)(methyl)amino)methyl)picolinate

[1440]

[1441] NaH (90.0 mg, 2.25 mmol) was added to a solution of methyl 5-(((tert-butoxycarbonyl)amino)methyl)picolinate (0.40 g, 1.5 mmol) in DMF (5 mL) at 0 °C and then stirred for 20 min. Mel (639.62 mg, 4.5 mmol) was added to the reaction mixture and then the reaction was warmed to rt and stirred for 1 h. The reaction was quenched with saturated NH4CI and the extracted with ethyl acetate. The combined extracted was dried and concentrated and then purified by chromatography, eluting with EtOAc in hexanes (0 to 100%) to afford the desired product. LCMS calculated for C14H21N2O4 (M+H)+m / z = 281.1; found (M+H)+m / z = 281.1.

[1442] Step 3: N-methyl-5-((methylamino)methyl)picolinamide

[1443] MeNH₂ (2 N in THF, 1.5 mL) was added to a mixture of methyl 5-(((tert-butoxycarbonyl)(methyl)amino)methyl)picolinate (100.0 mg, 0.36 mmol) and 3, 4, 6, 7,8,9-hexahydro-2H-pyrimido[ 1,2 -a] pyrimidine (24.8 mg, 0.18 mmol) and then the reaction was stirred at rt for 1 h. The solvent was removed and the Boc protected intermediate was purified by column eluting with hexane / EtOAc (max. EA 100%). The intermediate was dissolved in CH2CI2 (0.5 mL) and then HC1 (4 N in dioxane, 0.5 mL) was added and stirred for 30 min. The solvent was removed to provide the product as HC1 salt. LCMS calculated for C9H14N3O (M+H)+m / z = 180.1; found (M+H)+m / z = 180.0.

[1444] Intermediate 34: N-Methyl-5-(2-(methylamino)ethyl)picolinamide

[1445]

[1446] Step 1: (E)-5-(2-ethoxyvinyl)-N-methylpicolinamide54057-0036W01 / SNV0027-W01 PATENT

[1447]

[1448] A mixture of 5-bromo-N-methylpicolinamide (430.0 mg, 2.0 mmol), 2-[(E)-2-ethoxyvinyl]-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (594.0 mg, 3.0 mmol), K3PO4 (1.27 g, 6.0 mmol) and XPhos Pd G2 (169.3 mg, 0.20 mmol) in dioxane / water (10 / 2 mb) was stirred at 70 °C for 3 h. The mixture was diluted with ethyl acetate and washed with water, the organic was dried and concentrated. The product was purified by silica gel column chromatography, eluting with EtOAc in hexanes (0 to 100%). LCMS calculated for C11H15N2O2 (M+H)+m / z = 207.1; found (M+H)+m / z = 207.1.

[1449] Step 2: N-methyl-5-(2-oxoethyl)picolinamide

[1450]

[1451] 6 N HC1 (1.5 mL) was added to a solution of (E)-5-(2-ethoxyvinyl)-N-methylpicolinamide (0.30 g, 1.46 mmol) in THF (3.0 mL) and then the reaction was stirred at 50 °C for 4 h. The solvent was removed, and the product was used in the next step directly. LCMS calculated for C9H11N2O2 (M+H)+m / z = 179.1; found (M+H)+m / z = 179.1.

[1452] Step 3: N-methyl-5-(2-(methylamino)ethyl)picolinamide

[1453] Ti(OzPr)4 (0.48 mL, 1.68 mmol) was added to a solution of N-methyl-5-(2-oxoethyl)picolinamide (0.15 g, 0.84 mmol) in methylamine solution (2.0 N in THF, 3.0 mL) and then stirred at 70 °C overnight. The reaction was cooled to rt and ethanol (2.0 mL) was added followed by adding NaBH₄ (100.0 mg, 2.5 mmol) and then stirred at rt for 30 min. The reaction was quenched by adding water and then filtered and washed with methanol. The product was then purified by prep-HPLC (column: Sunfire prep C18 column, 30* 150 mm, 5pm; mobile phase A: water (0.1% TFA), mobile phase B: acetonitrile; flow rate: 60 mL / min); eluted fractions were collected and lyophilized to provide the desired. LCMS calculated for C10H16N3O (M+H)+m / z = 194.1; found (M+H)+m / z = 194.1.

[1454] Intermediate 35. (l-(2-(Methylamino)ethyl)cyclopropyl)methanol

[1455]

[1456] Step 1: l-(2-((tert-butoxycarbonyl)amino)ethyl)cyclopropane-l-carboxylic acid54057-0036W01 / SNV0027-W01 PATENT

[1457]

[1458] BOC2O (2.53 g, 11.6 mmol) was added to a solution of l-(2-aminoethyl)cyclopropane-1-carboxylic acid (1.0 g, 7.74 mmol) (HC1 salt) and Na2COs (1.64 g, 15.5 mmol) in THF / Water (30 / 15 mL) and then stirred at rt for overnight. The reaction was cooled with icewater and adjusted PH ~ 2 by adding 1 N HC1, extracted with ethyl acetate. The combined extract was dried and concentrated. The product was purified by silica gel column chromatography, eluting with CH2Q2 in MeOH (0 to 10%). LCMS calculated for C11H20NO4 (M+H)+m / z = 230.1; found LCMS (M+H-56)+, 174.1

[1459] Step 2: (l-(2-(methylamino)ethyl)cyclopropyl)methanol

[1460] LAH (1.0 M in THF, 7.0 mL) was added to l-(2-((tert-butoxycarbonyl)amino)ethyl)-cyclopropane-1 -carboxylic acid (0.20 g, 0.87 mmol) and then the reaction was stirred at 70 °C for 6 h. The reaction was cooled and quenched with water (0.25 mL), 15% NaOH (0.25 mL) and water (0.75 mL) and then stirred for 30 min. The mixture was filtered through Celite. The solvent was removed, and the product was used in the next step directly.

[1461] Intermediate 36.2-(4-(2-(Methylamino)ethyl)piperidin-l-yl)acetonitrile

[1462]

[1463] To a solution of tert-butyl methyl(2-(piperidin-4-yl)ethyl)carbamate (80 mg, 0.33 mmol) in ACN (0.5 mL), 2-bromoacetonitrile (44 mg, 0.36 mmol), K2CO3 (91 mg, 0.66 mmol) were added under nitrogen atmosphere. The mixture was stirred at 80 °C for 2 hours. The mixture was diluted with ethyl acetate (10 mL), filtered by a pad of Celite. and concentrated under vacuum. The residue was then diluted by DCM / TFA 1: 1 (2 mL) and concentrated after 30 minutes. The yellow oil TFA salt was used directly into the next step without further purification. LC-MS calculated for C10H20N3 (M+H)+m / z = 182.2; found 182.2.

[1464] Intermediate 37.3-(4-(2-(Methylamino)ethyl)piperidin-l-yl)propanenitrile54057-0036W01 / SNV0027-W01 PATENT

[1465]

[1466] To a solution of tert-butyl methyl(2-(piperidin-4-yl)ethyl)carbamate (80 mg, 0.33 mmol) in ACN (0.5 mb), 3 -bromopropanenitrile (48 mg, 0.36 mmol), K2CO3 (91 mg, 0.66 mmol) were added under nitrogen atmosphere. The mixture was stirred at 80 °C for 2 hours. The mixture was diluted with ethyl acetate (10 mL), filtered by a pad of Celite. and concentrated under vacuum. The residue was then diluted by DCM / TFA 1: 1 (2 mL) and concentrated after 30 minutes. The yellow oil TFA salt was used directly into the next step without further purification. LC-MS calculated for C11H22N3 (M+H)+m / z = 196.2; found 196.2.

[1467] Intermediate 38.2-(l-Cyclopropylpiperidin-4-yl)-N-methylethan-l-amine

[1468]

[1469] To a solution of tert-butyl methyl(2-(piperidin-4-yl)ethyl)carbamate (80 mg, 0.33 mmol) in DCE / AcOH (20: 1, 0.5 mL), [l-(methoxymethoxy)cyclopropoxy]-trimethyl-silane (126 mg, 0.66 mmol), STAB (140 mg, 0.66 mmol) was added under nitrogen atmosphere. The mixture was stirred at 60 °C for 1 hour. The mixture was diluted with ethyl acetate (10 mL), filtered by a pad of Celite. and concentrated under vacuum. The residue was then diluted by DCM / TFA 1: 1 (2 mL) and concentrated after 30 minutes. The yellow oil TFA salt was used directly into the next step without further purification. LC-MS calculated for C11H23N2 (M+H)+m / z = 183.2; found 183.2.

[1470] Intermediate 39.3-Methyleneazetidine TFA salt

[1471]

[1472] To a solution of tert-butyl 3-methyleneazetidine-l -carboxylate (169 mg, 1.0 mmol) in DCM (2 mL), TFA (2 mL). The mixture was stirred at rt for 1 hour. The residue was then concentrated under vacuum. The yellow oil TFA salt was used directly into the next step without further purification.

[1473] Intermediate 40.3-(Propan-2-ylidene)azetidine54057-0036W01 / SNV0027-W01 PATENT

[1474]

[1475] To a solution of tert-butyl 3-methyleneazetidine-l -carboxylate (200 mg, 1.18 mmol) in DCM (2 mb), Grubbs 3rdCatalyst (CAS: 900169-53-1, 52 mg, 0.06 mmol), 2-methylbut-2-ene (1.26 mL, 11.8 mmol) was added under nitrogen atmosphere. The mixture was stirred at 40 °C overnight. The Boc-protect product was purified by column chromatography to give the desired product (110 mg, 47%), which was then diluted by DCM / TFA 1: 1 (2 mL) and concentrated after 30 minutes. The yellow oil TFA salt was used directly into the next step without further purification.

[1476] Intermediate 41. tert-Butyl 6-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-2H-spiro[benzofuran-3,4'-piperidine]-l'-carboxylate

[1477]

[1478] Step 1: tert-butyl 4-((2-bromo-5-chlorophenoxy)methyl)-3,6-dihydropyridine-l(2H)-carboxylate

[1479]

[1480] To a solution of 2-bromo-5-chlorophenol (1.18 mg, 5.7 mmol) in acetone (20 mL), tert-butyl 4-(chloromethyl)-3,6-dihydropyridine-l(2H)-carboxylate (1.1 g, 4.75 mmol), K2CO3 (1.97 g, 14.2 mmol) were added under nitrogen atmosphere. The mixture was stirred reflux overnight. The solvent was removed under vacuum, and the residue was purified by column chromatography to give the desired product (1.1 g, 58%) as a colorless oil.

[1481] Step 2: tert-butyl 6-chloro-2H-spiro[benzofuran-3,4'-piperidine]-r-carboxylate54057-0036W01 / SNV0027-W01 PATENT

[1482]

[1483] To a solution of tert-butyl 4-((2-bromo-5-chlorophenoxy)methyl)-3,6-dihydropyridine-l(2H) -carboxylate (150 mg, 0.37 mmol) in benzene (7.4 mb), BusSnH (163 mg, 0.56 mmol), AIBN (18 mg, 0.11 mmol) were added under nitrogen atmosphere. The mixture was stirred reflux for 2 hours. The solvent was removed under vacuum, and the residue was purified by column chromatography to give the desired product (100 mg, 83%) as a colorless oil.

[1484] Step 3: tert-butyl 6-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-...

Claims

54057-0036W01 / SNV0027-W01 PATENTWHAT IS CLAIMED IS:

1. A compound of Formula 1-0:1-0or a pharmaceutically acceptable salt thereof, wherein:STAT6L is a STAT6 binding moiety selected from:STAT6L-7 STAT6L-854057-0036W01 / SNV0027-W01 PATENT, and m, n, o, p, q, r, and t are each independently 0, 1, 2, 3, 4, 5, or 6;each ~ is independently a single bond or double bond;E3L is H or an E3 ubiquitin ligase binding moiety of formula E3L-1:E3L-1X1is N or CR1;X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12are each independently C orN; Y1, Y2, Y3, Y4, and Y5are each independently N, NH, N-RB, -O-, -S-, C=O, C(RB), or C(RB)2;Z1, Z2, and Z3are each independently C or N;W1and W2are independently selected from a bond, -C(O)-, -C(S)-, -S(O)2-, -S(O)-, -W3and W4are independently selected from a bond, -C(R°)2-, -O-, and -S-; orW3-W4is -CR°=CR°-;each Rzis independently selected from H, halo, and54057-0036W01 / SNV0027-W01 PATENTRing A is selected from C5-20 cycloalkyl, Ce-io aryl, 5-20 membered heterocycloalkyl, and 5-14 membered heteroaryl;Ring B1, Ring B2, Ring B3, Ring B8, Ring B9, Ring B10, and Ring B11 are each independently selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-14 membered heteroaryl;Ring B7 is selected from 14-membered heteroaryl and 14-20 membered heterocycloalkyl;Ring Cl is selected from C9-14 cycloalkyl, 9-14 membered heterocycloalkyl, and 9-10 membered heteroaryl;Ring C l 1 is selected from C4-14 cycloalkyl and 4-14 membered heterocycloalkyl; Ring C2, Ring C3, Ring C4, Ring C5, Ring C6, Ring C7, Ring C8, Ring C9, Ring CIO, and Ring C12 are each independently selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;Ring D3 is selected from C12-30 cycloalkyl, 12-30 membered heterocycloalkyl, and 12-14 membered tricyclic heteroaryl;Ring D8 is selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;Ring D9, Ring E4, and Ring F 10 are each independently selected from C4-14 cycloalkyl and 4-14 membered heterocycloalkyl;Ringis selected from C4-14 cycloalkyl and 4-14 membered heterocycloalkyl;Ring E5 and Ring E6 are each independently selected from C5-14 cycloalkyl, Ce-io aryl, 5-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;each Ring Z is independently selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;L1is a bond or C1-3 alkylene, wherein 1-2 methylene groups of the C1-3 alkylene are each independently and optionally replaced by -O-, -S-, -N(RL1)-, -C(O)-, -N(RL1)C(O)-, -54057-0036W01 / SNV0027-W01 PATENTN(RL1)C(O)N(RL1)-, -N(RL1)C(O)O-, -S(0)-, -S(0)2-, -S(O)(=NRL1)-, -S(O)2N(RL1)-, and -N(RL1)S(O)2N(RL1)-, and wherein the C1-3 alkylene of L1is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;each RL1is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;L is a bond or C1-20 alkylene, wherein 1-10 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, -N(R)S(O)2N(R)-, -C(RO)2-, -C(R°)=C(R0)-, -C=C-, or -Cy-;each -Cy- is independently selected from C3-30 cycloalkyl, Ce-io aryl, 4-30 membered heterocycloalkyl, and 5-14 membered heteroaryl, wherein the C3-30 cycloalkyl, Ce-io aryl, 4-30 membered heterocycloalkyl, and 5-14 membered heteroaryl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;Lc, LD, and LFare each independently selected from a bond and C1-6 alkylene, wherein 1-3 methylene groups of the C1-6 alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, -N(R)S(O)2N(R)-, -C(R°)=C(R0)-, -C=C-, or -Cy-, wherein the C1-6 alkylene of Lc, LD, and LFis optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;LBis Ci -10 alkylene, wherein 1-6 methylene groups of the Ci.10 alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, or -N(R)S(O)2N(R)-, wherein the Ci.10 alkylene ofLBis optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;LBDis Ci -10 alkylene, wherein 1-6 methylene groups of the CMO alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, -N(R)S(O)2N(R)-, -C(RO)2-, or -Cy-;R1is selected from H, D, halo, CN, C1-4 alkyl, Ci -4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;or, R1and one of RA, together with the atoms to which they are attached, form a C5-10 cycloalkyl, or 5-10 membered heterocycloalkyl group, wherein the C5-10 cycloalkyl, and 5-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;or, R1and L1, together with the atoms to which they are attached, form a C3-10 cycloalkyl, or 4-10 membered heterocycloalkyl group, wherein the C3-10 cycloalkyl, and 4-1054057-0036W01 / SNV0027-W01 PATENTmembered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;each RA, RB, Rc, RD, RE, RF, and Rzois independently selected from H, halo, Ci-6 alkyl, Ci-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -OR, -SF5, -SR, -NRR, -NRNR2, -NO2, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NRNR2, -C(O)NR(OR), -OC(O)R, -OC(O)NR2, -OC(O)OR, -OS(O)2R, -OS(O)2NR2, -NRC(O)R, -NRC(O)OR, -NRC(O)NR2, -NRS(O)2R, -NRS(O)2NR2, -NROR, -NRS(O)R, -NRS(O)NR2, -S(O)R, -S(O)2R, -S(O)NR2, -S(O)2NR2, -C(=NR)R, -C(=NR)NR2, -NRC(=NR)R, -NRC(=NR)NR2, -NRS(O)(=NR)R, -NRS(O)(=NR)NR2, =NR, -N=S(O)R2, -N=S(O)RNR2, -OS(O)(=NR)R, -S(O)(=NR)R, -S(O)(=NR)NR2, -C(O)NRS(O)2R, -C(O)NRS(O)2NR2, -S(O)2NRC(O)R, -NRS(O)NRC(O)R, and -P(O)RR, wherein the Ci6alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;or, two REgroups, together with the atoms to which they are attached, form a C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, or 5-10 membered heteroaryl group, wherein the C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;each R, R9A, R9B, R10A, R10B, R11A, R11B, R12A, and R12Bis independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;or, two R groups attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;54057-0036W01 / SNV0027-W01 PATENTeach R° is independently selected from H, halo, Ci-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa0, -SF5, -SRa0, -NRc0Rd0, -NRc0NRc0Rd0, -NO2, -C(O)Ra0, -C(O)ORa0, -C(O)NRc0Rd0, -C(O)NRc0NRc0Rd0, -C(O)NRc0(ORa0), -OC(O)Ra0, -OC(O)NRc0Rd0, -OC(O)ORa0, -OS(O)2Rb0, -OS(O)2NRc0Rd0, -NRc0C(O)Ra0, -NRc0C(O)ORa0, -NRc0C(O)NRc0Rd0, -NRc0S(O)2Rb0, -NRc0S(O)2NRc0Rd0, -NRc0ORa0, -NRc0S(O)Rb0, -NRc0S(O)NRc0Rd0, -S(O)Rb0, -S(O)2Rb0, -S(O)NRc0Rd0, -S(O)2NRc0Rd0, -C(=NRe0)Ra0, -C(=NRe0)NRc0Rd0, -NRc0C(=NRe0)Ra0, -NRc0C(=NRe0)NRc0Rd0, -NRc0S(O)(=NRe0)Rb0, -NRc0S(O)(=NRe0)NRc0Rd0, =NRe0, -N=S(O)(Rb0)2, -N=S(O)Rb0NRc0Rd0, -OS(O)(=NRe0)Rb0, -S(O)(=NRe0)Rb0, -S(O)(=NRe0)NRc0Rd0, -C(O)NRc0S(O)2Rb0, -C(O)NRc0S(O)2NRc0Rd0, -S(O)2NRc0C(O)Rb0, -NRc0S(O)NRc0C(O)Rb0, and -P(O)Rf0Rg0, wherein the C1-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R° are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;each Ra0, Rc0, and Rd0is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra0, Rc0, and Rd0are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;or, any Rc0and Rd0attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;each Rb0is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl,54057-0036W01 / SNV0027-W01 PATENT(4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb0are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;each Re0is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;each Rf0and Rg0are independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;each R0Ais independently selected from H, halo, C1-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa°A _S_SRaOA5_NRc0ARd0A _NRc°ANRc0ARd0A, _NQ2, -C(O)Ra0A, -C(O)ORa°A, -C(O)NRc0ARd0A, -C(O)NRc0ANRc0ARd0A, -C(O)NRc0A(ORa0A), -OC(O)Ra0A, -OC(O)NRc0ARd0A, -OC(O)ORa0A, -OS(O)2Rb0A, -OS(O)2NRc0ARd0A, -NRc0AC(O)Ra0A, -NRc0AC(O)ORa0A, -NRc0AC(O)NRc0ARd0A, -NRc0AS(O)2Rb0A, -NRc0AS(O)2NRc0ARd0A, -NRc0AORa0A, -NRc0AS(O)Rb0A, -NRc0AS(O)NRc0ARd0A, -S(O)Rb0A, -S(O)2Rb0A, -S(O)NRc0ARd0A, -S(O)2NRc0ARd0A, -C(=NRe0A)Ra0A, -C(=NRe0A)NRc0ARd0A, -NRc0AC(=NRe0A)Ra0A, -NRc0AC(=NRe0A)NRc0ARd0A, -NRc0AS(O)(=NRe0A)Rb0A, -NRc0AS(O)(=NRe0A)NRc0ARd0A, =NRe0A, -N=S(O)(Rb0A)2, -N=S(O)Rb0ANRc0ARd0A, -OS(O)(=NRe0A)Rb0A, -S(O)(=NRe0A)Rb0A, -S(O)(=NRe0A)NRc0ARd0A, -C(O)NRc0AS(O)2Rb0A, -C(O)NRc0AS(O)2NRc0ARd0A, -S(O)2NRc0AC(O)Rb0A, -NRc0AS(O)NRc0AC(O)Rb0A, and -P(O)RfflARg0A, wherein the Ci-6alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R0Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;each Ra0A, Rc0A, and Rd0Ais independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-654057-0036W01 / SNV0027-W01 PATENTalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra0A, Rc0A, and Rd0Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;or, any Rc0Aand Rd0Aattached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;each Rb0Ais independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb0Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;each Re0Ais independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;each Rf0Aand Rg0Aare independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;each R0Bis independently selected from H, halo, C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -54057-0036W01 / SNV0027-W01 PATENTNRc0BS(O)Rb0B, -NRc0BS(O)NRc0BRd0B, -S(O)Rb0B, -S(O)2Rb0B, -S(O)NRc0BRd0B, -S(O)2NRc0BRd0B, -C(=NRe0B)Ra0B, -C(=NRe0B)NRc0BRd0B, -NRc0BC(=NRe0B)Ra0B, -NRc0BC(=NRe0B)NRc0BRd0B, -NRc0BS(O)(=NRe0B)Rb0B, -NRc0BS(O)(=NRe0B)NRc0BRd0B, -OS(O)(=NRe0B)Rb0B, -S(O)(=NRe0B)Rb0B, -S(O)(=NRe0B)NRc0BRd0B, -C(O)NRc0BS(O)2Rb0B, -C(O)NRc0BS(O)2NRc0BRd0B, -S(O)2NRc0BC(O)Rb0B, -NRc0BS(O)NRc0BC(O)Rb0B, and -P(O)Rf0BRg0B, wherein the Ci-6 alkyl, Ci-6 alkylidenyl, C2.6 alkenyl, C2.6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R0Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;each Ra0B, Rc0B, and Rd0Bis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2.6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra0B, Rc0B, and Rd0Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;or, any Rc0Band Rd0Battached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;each Rb0Bis independently selected from C1-6 alkyl, C1-6 haloalkyl, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb0Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;each Re0Bis independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-54057-0036W01 / SNV0027-W01 PATENTCI-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;each Rf0Band Rg0Bare independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; andeach RGis independently selected from H, OH, CN, halo, C1-4 alkyl, Ci-4alkylidenyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-Ci.4 alkyl, HO-C1.4 alkyl, C1-4 alkoxy-Ci.4 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, C1-3 alkylthio, C1-3 alkylsulfmyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, aminocarbonyloxy, C1-3 alkylaminocarbonyloxy, di(Ci-3 alkyl)aminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(Ci-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(Ci-3 alkyl)aminocarbonylamino.

2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, which is a compound of Formula I:wherein:STAT6L is a STAT6 binding moiety selected from:54057-0036W01 / SNV0027-W01 PATENTm, n, o, p, q, r, and t are each independently 0, 1, 2, 3, 4, 5, or 6;each ~ is independently a single bond or double bond;X1is N or CR1;X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12are each independently C orN; Y1, Y2, Y3, Y4, and Y5are each independently N, NH, N-RB, -O-, -S-, C=O, C(RB), or C(RB)2;Z1, Z2, and Z3are each independently C or N;each Rzis independently selected from H, halo, and54057-0036W01 / SNV0027-W01 PATENTRing A is selected from C5-20 cycloalkyl, Ce-io aryl, 5-20 membered heterocycloalkyl, and 5-14 membered heteroaryl;Ring B1, Ring B2, Ring B3, Ring B8, Ring B9, Ring B10, and Ring B11 are each independently selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-14 membered heteroaryl;Ring B7 is selected from 14-membered heteroaryl and 14-20 membered heterocycloalkyl;Ring Cl is selected from C9-14 cycloalkyl, 9-14 membered heterocycloalkyl, and 9-10 membered heteroaryl;Ring C l 1 is selected from C4-14 cycloalkyl and 4-14 membered heterocycloalkyl; Ring C2, Ring C3, Ring C4, Ring C5, Ring C6, Ring C7, Ring C8, Ring C9, Ring CIO, and Ring C12 are each independently selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;Ring D3 is selected from C12-20 cycloalkyl, 12-20 membered heterocycloalkyl, and 12-14 membered tricyclic heteroaryl;Ring D8 is selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;Ring D9, Ring E4, and Ring F 10 are each independently selected from C4-14 cycloalkyl and 4-14 membered heterocycloalkyl;Ringis selected from C4-14 cycloalkyl and 4-14 membered heterocycloalkyl;Ring E5 and Ring E6 are each independently selected from C5-14 cycloalkyl, Ce-io aryl, 5-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;each Ring Z is independently selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;L1is a bond or C1-3 alkylene, wherein 1-2 methylene groups of the C1-3 alkylene are each independently and optionally replaced by -O-, -S-, -N(RL1)-, -C(O)-, -N(RL1)C(O)-, -54057-0036W01 / SNV0027-W01 PATENTN(RL1)C(O)N(RL1)-, -N(RL1)C(O)O-, -S(0)-, -S(0)2-, -S(O)(=NRL1)-, -S(O)2N(RL1)-, and -N(RL1)S(O)2N(RL1)-, and wherein the C1-3 alkylene of L1is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;each RL1is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;L is a bond or C1-20 alkylene, wherein 1-10 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, -N(R)S(O)2N(R)-, -C(RO)2-, -C(R°)=C(R0)-, -C=C-, or -Cy-;each -Cy- is independently selected from C3-20cycloalkyl, Ce-io aryl, 4-20 membered heterocycloalkyl, and 5-14 membered heteroaryl, wherein the C3-20cycloalkyl, C6-10aryl, 4-20 membered heterocycloalkyl, and 5-14 membered heteroaryl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;Lc, LD, and LFare each independently selected from a bond and C1-6 alkylene, wherein 1-3 methylene groups of the C1-6 alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, -N(R)S(O)2N(R)-, -C(R°)=C(R0)-, -C=C-, or -Cy-, wherein the C1-6 alkylene of Lc, LD, and LFis optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;LBis Ci -10 alkylene, wherein 1-6 methylene groups of the Ci.10 alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, or -N(R)S(O)2N(R)-, wherein the Ci.10 alkylene ofLBis optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;LBDis Ci -10 alkylene, wherein 1-6 methylene groups of the CMO alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, -N(R)S(O)2N(R)-, -C(RO)2-, or -Cy-;R1is selected from H, D, halo, CN, C1-4 alkyl, Ci -4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;each RA, RB, Rc, RD, RE, RF, and Rzois independently selected from H, halo, C1-6 alkyl, C1-6 alkylidenyl, C2-6alkenyl, C2-6alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -OR, -SF5, -SR, -NRR, -NO2, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NR(OR), -OC(O)R, -OC(O)NR2, -OC(O)OR, -OS(O)2R, -OS(O)2NR2, -NRC(O)R, -NRC(O)OR, -NRC(O)NR2, -NRS(O)2R, -NRS(O)2NR2, -NROR, -NRS(O)R, -NRS(O)NR2, -S(O)R, -54057-0036W01 / SNV0027-W01 PATENTS(O)2R, -S(O)NR2, -S(O)2NR2, -C(=NR)R, -C(=NR)NR2, -NRC(=NR)R, -NRC(=NR)NR2, -NRS(O)(=NR)R, -NRS(O)(=NR)NR2, =NR, -N=S(O)R2, -N=S(O)RNR2, -OS(O)(=NR)R, -S(O)(=NR)R, -S(O)(=NR)NR2, -C(O)NRS(O)2R, -C(O)NRS(O)2NR2, -S(O)2NRC(O)R, -NRS(O)NRC(O)R, and -P(O)RR, wherein the Ci-6 alkyl, Ci-6 alkylidenyl, C2.6 alkenyl, C2.6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;or, two REgroups, together with the atoms to which they are attached, form a C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, or 5-10 membered heteroaryl group, wherein the C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;each R, R9A, R9B, R10A, R10B, R11A, R11B, R12A, and R12Bis independently selected from H, C1-6 alkyl, C2.6 alkenyl, C2.6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2.6 alkenyl, C2.6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;or, two R groups attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;each R° is independently selected from H, halo, C1-6 alkyl, Ci -6 alkylidenyl, C2.6 alkenyl, C2.6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa0, -SF5, -SRa0, -NRc0Rd0, -NO2, -C(O)Ra0, -C(O)ORa0, -C(O)NRc0Rd0, -C(O)NRc0(ORa0), -OC(O)Ra0, -OC(O)NRc0Rd0, -OC(O)ORa0, -OS(O)2Rb0, -OS(O)2NRc0Rd0, -NRc0C(O)Ra0, -NRc0C(O)ORa0, -NRc0C(O)NRc0Rd0, -NRc0S(O)2Rb0, -NRc0S(O)2NRc0Rd0, -NRc0ORa0, -NRc0S(O)Rb0, -NRc0S(O)NRc0Rd0, -S(O)Rb0, -S(O)2Rb0, -S(O)NRc0Rd0, -S(O)2NRc0Rd0, -C(=NRe0)Ra0, -C(=NRe0)NRc0Rd0, -NRc0C(=NRe0)Ra0, -NRc0C(=NRe0)NRc0Rd0, -NRc0S(O)(=NRe0)Rb0, -NRc0S(O)(=NRe0)NRc0Rd0, =NRe0, -N=S(O)(Rb0)2, -54057-0036W01 / SNV0027-W01 PATENTN=S(O)Rb0NRc0Rd0, -OS(O)(=NRe0)Rb0, -S(O)(=NRe0)Rb0, -S(O)(=NRe0)NRc0Rd0, -C(O)NRc0S(O)2Rb0, -C(O)NRc0S(O)2NRc0Rd0, -S(O)2NRc0C(O)Rb0, -NRc0S(O)NRc0C(O)Rb0, and -P(O)Rf0Rg0, wherein the Ci-6 alkyl, Ci-6 alkylidenyl, C2.6 alkenyl, C2.6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R° are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;each Ra0, Rc0, and Rd0is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2.6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra0, Rc0and Rd0are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;or, any Rc0and Rd0attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;each Rb0is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb0are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;each Re0is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;each Rf0and Rg0are independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-1054057-0036W01 / SNV0027-W01 PATENTmembered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;each R0Ais independently selected from H, halo, C1-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -NRc0AS(O)NRc0AC(O)Rb0A, and -P(O)Rf0ARg0A, wherein the Ci-6alkyl, Ci-ealkylidenyl, C2-6alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R0Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;each Ra0A, Rc0A, and Rd0Ais independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra0A, Rc0A, and Rd0Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;or, any Rc0Aand Rd0Aattached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;54057-0036W01 / SNV0027-W01 PATENTeach Rb0Ais independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb0Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;each Re0Ais independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;each Rf0Aand Rg0Aare independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;each R0Bis independently selected from H, halo, C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa0B, -SF5, -SRa0B, -NRc0BRd0B, -NO2, -C(O)Ra0B, -C(O)ORa0B, -C(O)NRc0BRd0B, -C(O)NRc0B(ORa0B), -OC(O)Ra0B, -OC(O)NRc0BRd0B, -OC(O)ORa0B, -OS(O)2Rb0B, -OS(O)2NRc0BRd0B, -NRc0BC(O)Ra0B, -NRc0BC(O)ORa0B, -NRc0BC(O)NRc0BRd0B, -NRc0BS(O)2Rb0B, -NRc0BS(O)2NRc0BRd0B, -NRc0BORa0B, -NRc0BS(O)Rb0B, -NRc0BS(O)NRc0BRd0B, -S(O)Rb0B, -S(O)2Rb0B, -S(O)NRc0BRd0B, -S(O)2NRc0BRd0B, -C(=NRe0B)Ra0B, -C(=NRe0B)NRc0BRd0B, -NRc0BC(=NRe0B)Ra0B, -NRc0BC(=NRe0B)NRc0BRd0B, -NRc0BS(O)(=NRe0B)Rb0B, -NRc0BS(O)(=NRe0B)NRc0BRd0B, -OS(O)(=NRe0B)Rb0B, -S(O)(=NRe0B)Rb0B, -S(O)(=NRe0B)NRc0BRd0B, -C(O)NRc0BS(O)2Rb0B, -C(O)NRc0BS(O)2NRc0BRd0B, -S(O)2NRc0BC(O)Rb0B, -NRc0BS(O)NRc0BC(O)Rb0B, and -P(O)Rf0BRg0B, wherein the C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered54057-0036W01 / SNV0027-W01 PATENTheterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R0Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;each Ra0B, Rc0B, and Rd0Bis independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra0B, Rc0B, and Rd0Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;or, any Rc0Band Rd0Battached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;each Rb0Bis independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb0Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;each Re0Bis independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;each Rf0Band Rg0Bare independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; andeach RGis independently selected from H, OH, CN, halo, C1-4 alkyl, Ci-4alkylidenyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-Ci.4 alkyl, HO-C1.4 alkyl, C1-4 alkoxy-Ci.454057-0036W01 / SNV0027-W01 PATENTalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, C1-3 alkylthio, C1-3 alkylsulfmyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, aminocarbonyloxy, C1-3 alkylaminocarbonyloxy, di(Ci-3 alkyl)aminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(Ci-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(Ci-3 alkyl)aminocarbonylamino.

3. The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, which is a compound of Formula I:wherein:STAT6L is a STAT6 binding moiety selected from:54057-0036W01 / SNV0027-W01 PATENTm, n, o, p, q, r, and t are each independently 0, 1, 2, 3, 4, 5, or 6;each ~ is independently a single bond or double bond;X1is N or CR1;X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12are each independently C orN; Y1, Y2, Y3, Y4, and Y5are each independently N, NH, N-RB, -O-, -S-, C=O, C(RB), or C(RB)2;Z1, Z2, and Z3are each independently C or N;each Rzis independently selected from H, halo, and54057-0036W01 / SNV0027-W01 PATENTRing A is selected from C5-14 cycloalkyl, Ce-io aryl, 5-14 membered heterocycloalkyl, and 5-14 membered heteroaryl;Ring B1, Ring B2, Ring B3, Ring B8, Ring B9, Ring B10, and Ring B11 are each independently selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-14 membered heteroaryl;Ring B7 is selected from 14-membered heteroaryl and 14-20 membered heterocycloalkyl;Ring Cl is selected from C9-14 cycloalkyl, 9-14 membered heterocycloalkyl, and 9-10 membered heteroaryl;Ring Cl 1 is selected from C4-14 cycloalkyl and 4-14 membered heterocycloalkyl; Ring C2, Ring C3, Ring C4, Ring C5, Ring C6, Ring C7, Ring C8, Ring C9, Ring CIO, and Ring C12 are each independently selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;Ring D3 is selected from C12-20 cycloalkyl, 12-20 membered heterocycloalkyl, and 12-14 membered tricyclic heteroaryl;Ring D8 is selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;Ring D9, Ring E4, and Ring F 10 are each independently selected from C4-14 cycloalkyl and 4-14 membered heterocycloalkyl;Ringis selected from C4-14 cycloalkyl and 4-14 membered heterocycloalkyl;Ring E5 and Ring E6 are each independently selected from C5-14 cycloalkyl, Ce-io aryl, 5-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;each Ring Z is independently selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl;L1is a bond or C1-3 alkylene, wherein 1-2 methylene groups of the C1-3 alkylene are each independently and optionally replaced by -O-, -S-, -N(RL1)-, -C(O)-, -N(RL1)C(O)-, -N(RL1)C(O)N(RL1)-, -N(RL1)C(O)O-, -S(O)-, -S(O)2-, -S(O)(=NRL1)-, -S(O)2N(RL1)-, and -N(RL1)S(O)2N(RL1)-, and wherein the C1-3 alkylene of L1is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;each RL1is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;L is a bond or C1-20 alkylene, wherein 1-10 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -54057-0036W01 / SNV0027-W01 PATENTN(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(0)-, -S(0)2-, -S(O)(=NR)-, -S(O)2N(R)-, -N(R)S(O)2N(R)-, -C(RO)2-, or -Cy-;each -Cy- is independently selected from C3-20cycloalkyl, Ce-io aryl, 4-20 membered heterocycloalkyl, and 5-14 membered heteroaryl, wherein the C3-20cycloalkyl, C6-10aryl, 4-20 membered heterocycloalkyl, and 5-14 membered heteroaryl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;Lc, LD, and LFare each independently selected from a bond and Ci-6 alkylene, wherein 1-3 methylene groups of the Ci-6 alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, or -N(R)S(O)2N(R)-, wherein the Ci-6alkylene of Lc, LD, and LFis optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;LBis Ci -io alkylene, wherein 1-6 methylene groups of the C O alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, or -N(R)S(O)2N(R)-, wherein the CMO alkylene ofLBis optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;LBDis Ci -io alkylene, wherein 1-6 methylene groups of the C O alkylene are each independently and optionally replaced by -O-, -S-, -N(R)-, -C(O)-, -N(R)C(O)-, -N(R)C(O)N(R)-, -N(R)C(O)O-, -P(O)R-, -S(O)-, -S(O)2-, -S(O)(=NR)-, -S(O)2N(R)-, -N(R)S(O)2N(R)-, -C(RO)2-, or -Cy-;R1is selected from H, D, halo, CN, Ci-4 alkyl, Ci.4haloalkyl, CM alkoxy, and CM haloalkoxy;each RA, RB, Rc, RD, RE, RF, and Rzois independently selected from H, halo, CM alkyl, Ci-6 alkylidenyl, C2.6 alkenyl, C2.ealkynyl, CM haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci.4 alkyl, Ce-io aryl-Ci.4 alkyl, (4-10 membered heterocycloalkyl) -CM alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -OR, -SF5, -SR, -NRR, -NO2, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NR(OR), -OC(O)R, -OC(O)NR2, -OC(O)OR, -OS(O)2R, -OS(O)2NR2, -NRC(O)R, -NRC(O)OR, -NRC(O)NR2, -NRS(O)2R, -NRS(O)2NR2, -NROR, -NRS(O)R, -NRS(O)NR2, -S(O)R, -S(O)2R, -S(O)NR2, -S(O)2NR2, -C(=NR)R, -C(=NR)NR2, -NRC(=NR)R, -NRC(=NR)NR2, -NRS(O)(=NR)R, -NRS(O)(=NR)NR2, -OS(O)(=NR)R, -S(O)(=NR)R, -S(O)(=NR)NR2, -C(O)NRS(O)2R, -C(O)NRS(O)2NR2, -S(O)2NRC(O)R, -NRS(O)NRC(O)R, and -P(O)RR, wherein the CM alkyl, Ci- 6 alkylidenyl, CM alkenyl, C alkynyl, CM haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci.4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and54057-0036W01 / SNV0027-W01 PATENT(5-10 membered heteroaryl)-Ci-4 alkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;or, two REgroups, together with the atoms to which they are attached, form a C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, or 5-10 membered heteroaryl group, wherein the C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;each R, R9A, R9B, R10A, R10B, R11A, R11B, R12A, and R12Bis independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;or, two R groups attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;each R° is independently selected from H, halo, C1-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa0, -SF5, -SRa0, -NRc0Rd0, -NO2, -C(O)Ra0, -C(O)ORa0, -C(O)NRc0Rd0, -C(O)NRc0(ORa0), -OC(O)Ra0, -OC(O)NRc0Rd0, -OC(O)ORa0, -OS(O)2Rb0, -OS(O)2NRc0Rd0, -NRc0C(O)Ra0, -NRc0C(O)ORa0, -NRc0C(O)NRc0Rd0, -NRc0S(O)2Rb0, -NRc0S(O)2NRc0Rd0, -NRc0ORa0, -NRc0S(O)Rb0, -NRc0S(O)NRc0Rd0, -S(O)Rb0, -S(O)2Rb0, -S(O)NRc0Rd0, -S(O)2NRc0Rd0, -C(=NRe0)Ra0, -C(=NRe0)NRc0Rd0, -NRc0C(=NRe0)Ra0, -NRc0C(=NRe0)NRc0Rd0, -NRc0S(O)(=NRe0)Rb0, -NRc0S(O)(=NRe0)NRc0Rd0, -OS(O)(=NRe0)Rb0, -S(O)(=NRe0)Rb0, -S(O)(=NRe0)NRc0Rd0, -C(O)NRc0S(O)2Rb0, -C(O)NRc0S(O)2NRc0Rd0, -S(O)2NRc0C(O)Rb0, -NRc0S(O)NRc0C(O)Rb0, and -P(O)Rf0Rg0, wherein the C1-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R° are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;54057-0036W01 / SNV0027-W01 PATENTeach Ra0, Rc0, and Rd0is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra0, Rc0and Rd0are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;or, any Rc0and Rd0attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;each Rb0is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb0are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Asubstituents;each Re0is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;each Rf0and Rg0are independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;each R0Ais independently selected from H, halo, C1-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -54057-0036W01 / SNV0027-W01 PATENTC(O)NRc0AS(O)2NRc0ARd0A, -S(O)2NRc0AC(O)Rb0A, -NRc0AS(O)NRc0AC(O)Rb0A, and -P(O)Rf0ARg0A, wherein the Ci-6 alkyl, Ci-ealkylidenyl, C2.6 alkenyl, C2.6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R0Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;each Ra0A, Rc0A, and Rd0Ais independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2.6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra0A, Rc0A, and Rd0Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;or, any Rc0Aand Rd0Aattached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;each Rb0Ais independently selected from C1-6 alkyl, C1-6 haloalkyl, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2.6 alkenyl, C2.6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb0Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R0Bsubstituents;54057-0036W01 / SNV0027-W01 PATENTeach Re0Ais independently selected from H, OH, CN, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;each Rf0Aand Rg0Aare independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;each R0Bis independently selected from H, halo, C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -C(O)NRc0BS(O)2NRc0BRd0B, -S(O)2NRc0BC(O)Rb0B, -NRc0BS(O)NRc0BC(O)Rb0B, and -P(O)Rf0BRg0B, wherein the C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R0Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;each Ra0B, Rc0B, and Rd0Bis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of54057-0036W01 / SNV0027-W01 PATENTRa0B, Rc0B, and Rd0Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;or, any Rc0Band Rd0Battached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;each Rb0Bis independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb0Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;each Re0Bis independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;each Rf0Band Rg0Bare independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; andeach RGis independently selected from H, OH, CN, halo, C1-4 alkyl, Ci-4alkylidenyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-Ci.4 alkyl, HO-C1.4 alkyl, C1-4 alkoxy-Ci.4 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, C1-3 alkylthio, C1-3 alkylsulfmyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, aminocarbonyloxy, C1-3 alkylaminocarbonyloxy, di(Ci-3 alkyl)aminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(Ci-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(Ci-3 alkyl)aminocarbonylamino.54057-0036W01 / SNV0027-W01 PATENT4. The compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, wherein STAT6L is a STAT6 binding moiety selected fromSTAT6L-6A STAT6L-754057-0036W01 / SNV0027-W01 PATENTwherein • / vvvvvv' refers to the bond between STAT6L and L.

5. The compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt54057-0036W01 / SNV0027-W01 PATENT54057-0036W01 / SNV0027-W01 PATENT54057-0036W01 / SNV0027-W01 PATENT54057-0036W01 / SNV0027-W01 PATENT54057-0036W01 / SNV0027-W01 PATENT54057-0036W01 / SNV0027-W01 PATENT54057-0036W01 / SNV0027-W01 PATENT54057-0036W01 / SNV0027-W01 PATENT54057-0036W01 / SNV0027-W01 PATENTwherein <~vwvv' refers to the bond between STAT6L and L.

6. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein LBis C O alkylene.

7. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein LBis C1-3 alkylene.

8. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein LBis -CH2-.

9. The compound of any one of claims 1 to 8, or a pharmaceutically acceptable saltthereof, wherein10. The compound of any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, wherein Ring C2 is 4-14 membered heterocycloalkyl or 5-10 membered heteroaryl.

11. The compound of any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, wherein Ring C2 is 4-7 membered heterocycloalkyl or 5-10 membered heteroaryl.

12. The compound of any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, wherein Ring C2 is pyrrolidinyl or pyridinyl.54057-0036W01 / SNV0027-W01 PATENT13. The compound of any one of claims 1 to 12, or a pharmaceutically acceptable saltthereof, wherein14. The compound of any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein Ring C7 is 4-14 membered heterocycloalkyl.

15. The compound of any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein Ring C7 is 1,2,3,6-tetrahydropyridinyl.

16. The compound of any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein RZ7is -Lc-Rz.

17. The compound of any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein Lcis selected from a bond and Ci-6 alkylene, wherein 1 or 2 methylene groups are each independently and optionally replaced by -C(O)-.

18. The compound of any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein Lcis selected from a bond and C1-3 alkylene, wherein 1 or 2 methylene groups are each independently and optionally replaced by -C(O)-.

19. The compound of any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein Lcis selected from a bond, -CH2, -CH2CH2-, -C(0)CH2- and -CTUCITC O)-.

20. The compound of any one of claims 1 to 19, or a pharmaceutically acceptable saltthereof, wherein Rzis selected from H and21. The compound of any one of claims 1 to 20, or a pharmaceutically acceptable salt thereof, wherein Ring Z is selected from 4-14 membered heterocycloalkyl and 5-10 membered heteroaryl.54057-0036W01 / SNV0027-W01 PATENT22. The compound of any one of claims 1 to 20, or a pharmaceutically acceptable salt thereof, wherein Ring Z is selected from 8-14 membered heterocycloalkyl and 5-6 membered heteroaryl.

23. The compound of any one of claims 1 to 20, or a pharmaceutically acceptable salt thereof, wherein Ring Z is selected from l,5,8,8a-tetrahydroimidazo[l,5-a]pyridin-3(2H)-onyl, 2,7-diazaspiro[4.5]decan-l-onyl, pyrazolyl, and triazolyl.

24. The compound of any one of claims 1 to 23, or a pharmaceutically acceptable salt thereof, wherein t is 0 or 1.

25. The compound of any one of claims 1 to 20, or a pharmaceutically acceptable saltthereof, wherein Ring Z is selected from26. The compound of any one of claims 1 to 25, or a pharmaceutically acceptable salt thereof, wherein each RZ0is independently selected from Ci-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-ealkynyl, and C1-6 haloalkyl.

27. The compound of any one of claims 1 to 25, or a pharmaceutically acceptable salt thereof, wherein each Rzois independently selected from C1-3 alkyl.

28. The compound of any one of claims 1 to 19, or a pharmaceutically acceptable saltthereof, wherein Rzis selected from29. The compound of any one of claims 1 to 28, or a pharmaceutically acceptable salt thereof, wherein each RB, Rc, RD, RE, and RFis independently selected from H, halo, C1-654057-0036W01 / SNV0027-W01 PATENTalkyl, Ci-6 alkylidenyl, C2-6 alkenyl, C2-ealkynyl, C1-6 haloalkyl, -C(O)R, -C(0)NR2, and -C(O)NRNR2;each R is independently selected from H, C1-6 alkyl, 4-10 membered heterocycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, 4-10 membered heterocycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;each R° is independently selected from H, C1-6 alkyl, Ci -6 alkylidenyl, C3-10 cycloalkyl, and -C(O)NRc0Rd0, wherein each C1-6 alkyl is optionally substituted with OH or CN; and each Rc0and Rd0is independently selected from H and C1-6 alkyl.

30. The compound of any one of claims 1 to 28, or a pharmaceutically acceptable salt thereof, wherein each RB, Rc, RD, RE, and RFis independently selected from H, halo, C1-6 alkyl, -C(O)R, -C(O)NR2, -C(O)NRNR2;each R is independently selected from H, C1-3 alkyl, 4-7 membered heterocycloalkyl, C3-7 cycloalkyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, 4-7 membered heterocycloalkyl, C3-7 cycloalkyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;each R° is independently selected from H, C1-6 alkyl, Ci- 6 alkylidenyl, C3-7 cycloalkyl, and -C(O)NRc0Rd0, wherein each C1-6 alkyl is optionally substituted with OH or CN; and each Rc0and Rd0is independently selected from H and C1-6 alkyl.

31. The compound of any one of claims 1 to 28, or a pharmaceutically acceptable salt thereof, wherein each RB, Rc, RD, RE, and RFis independently selected from H, methyl,fluoro,54057-0036W01 / SNV0027-W01 PATENT32. The compound of any one of claims 1 to 31, or a pharmaceutically acceptable salt thereof, wherein LBDis Ci- 10 alkylene, wherein 1-6 methylene groups of the Ci- 10 alkylene are each independently and optionally replaced by -O- or -N(R)C(O)-; andeach R is independently selected from H and C1-6 alkyl.

33. The compound of any one of claims 1 to 31, or a pharmaceutically acceptable salt thereof, wherein LBDis C3-7 alkylene, wherein 2-4 methylene groups of the C3-7 alkylene are each independently and optionally replaced by -O- or -N(R)C(O)-; andeach R is independently selected from H and C1-3 alkyl.

34. The compound of any one of claims 1 to 31, or a pharmaceutically acceptable salt thereof, wherein LBDis -C(O)N(CH3)-CH2CH2-O-.

35. The compound of any one of claims 1 to 34, or a pharmaceutically acceptable salt thereof, wherein R10Aand R10Bare each H.

36. The compound of any one of claims 1 to 35, or a pharmaceutically acceptable salt thereof, wherein R12Aand R12Bare each independently selected from H and 5-6 membered heteroaryl, wherein the 5-6 membered heteroaryl is optionally substituted with 1 or 2 R° substituents independently selected from C1-6 alkyl.

37. The compound of any one of claims 1 to 36, or a pharmaceutically acceptable salt thereof, wherein L is a bond or C1-20 alkylene, wherein 1-10 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -Cy-, -NH-, -N(CH3)-, or -C(O)-; and54057-0036W01 / SNV0027-W01 PATENTeach Cy is independently selected from C3-10 cycloalkyl, Ce-io aryl, and 4-20 membered heterocycloalkyl, wherein the C3-10 cycloalkyl, Ce-io aryl, and 4-20 membered heterocycloalkyl are each optionally substituted with 1 or 2 R° substituents.

38. The compound of any one of claims 1 to 36, or a pharmaceutically acceptable salt thereof, wherein L is a bond or C O alkylene, wherein 1-5 methylene groups of the C O alkylene are each independently and optionally replaced by -Cy-, -NH-, -N(CHs)-, or -C(O)-; andeach Cy is independently selected from C3-7 cycloalkyl, phenyl, and 4-20 membered heterocycloalkyl wherein the C3-7 cycloalkyl, phenyl, and 4-20 membered heterocycloalkyl are each optionally substituted with 1 or 2 R° substituents.

39. The compound of any one of claims 1 to 36, or a pharmaceutically acceptable salt thereof, wherein L is a bond or CMO alkylene, wherein 1-5 methylene groups of the CMO alkylene are each independently and optionally replaced by -Cy-, -NH-, -N(CH3)-, or -C(O)-; andeach Cy is independently selected from cyclohexyl, phenyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, 3H-spiro[isobenzofuran-l,4'-piperidinyl], 1,2, 3, 4, 4a, 5-hexahydrobenzo [b]pyrazino [ 1,2-d] [ 1,4]oxazinyl, 2,3 -dihydrospiro [indene- 1,4'-piperidinyl], and 2,8-diazaspiro[4.5]decanyl, wherein the cyclohexyl, phenyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, 3H-spiro[isobenzofuran-l,4'-piperidinyl], 1,2, 3, 4, 4a, 5-hexahydrobenzo [b]pyrazino [ 1,2-d] [ 1,4]oxazinyl, 2,3 -dihydrospiro [indene- 1,4'-piperidinyl], and 2,8-diazaspiro[4.5]decanyl are each optionally substituted with 1 or 2 R° substituents independently selected from halo and C1-6 alkoxy.

40. The compound of any one of claims 1 to 36, or a pharmaceutically acceptable saltthereof, wherein L is selected from a bond, -CH2CH2-, -CH2CH2CH2-,54057-0036W01 / SNV0027-W01 PATENT54057-0036W01 / SNV0027-W01 PATENT41. The compound of any one of claims 1 to 40, or a pharmaceutically acceptable salt thereof, wherein E3L is an E3 ubiquitin ligase binding moiety of formula E3L-1:E3L-142. The compound of any one of claims 1 to 41, or a pharmaceutically acceptable salt thereof, wherein Ring A is selected from Ce-io aryl, 5-14 membered heterocycloalkyl, and 5-14 membered heteroaryl.

43. The compound of any one of claims 1 to 41, or a pharmaceutically acceptable salt thereof, wherein Ring A is selected from phenyl, 8-10 membered heterocycloalkyl, and 8-10 membered heteroaryl.

44. The compound of any one of claims 1 to 41, or a pharmaceutically acceptable salt thereof, wherein Ring A is selected from phenyl, indazolyl, and l,3-dihydro-2H-benzo [d]imidazol-2-onyl.54057-0036W01 / SNV0027-W01 PATENT45. The compound of any one of claims 1 to 44, or a pharmaceutically acceptable salt thereof, wherein m is 0, 1, or 2.

46. The compound of any one of claims 1 to 45, or a pharmaceutically acceptable salt thereof, wherein each RAis independently selected from halo, Ci-6 alkyl, Ci-6 alkylidenyl, C2-6 alkenyl, C2-ealkynyl, and C1-6 haloalkyl.

47. The compound of any one of claims 1 to 45, or a pharmaceutically acceptable salt thereof, wherein each RAis independently selected from halo, Ci- 6 alkyl, and C1-6 haloalkyl.

48. The compound of any one of claims 1 to 45, or a pharmaceutically acceptable salt thereof, wherein each RAis independently selected from fluoro, chloro, and methyl.

49. The compound of any one of claims 1 to 41, or a pharmaceutically acceptable saltthereof, wherein Ring A is selected from50. The compound of any one of claims 1 to 49, or a pharmaceutically acceptable salt thereof, wherein L1is a bond.

51. The compound of any one of claims 1 to 50, or a pharmaceutically acceptable salt thereof, wherein X1is CH.

52. The compound of any one of claims 1 to 50, or a pharmaceutically acceptable salt thereof, wherein X1is N.54057-0036W01 / SNV0027-W01 PATENT53. The compound of any one of claims 1 to 50, or a pharmaceutically acceptable saltthereof, wherein54. The compound of any one of claims 1 to 40, or a pharmaceutically acceptable salt thereof, wherein E3L is H.

55. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:E3L is H or an E3 ubiquitin ligase binding moiety of formula E3L-1:54057-0036W01 / SNV0027-W01 PATENTSTAT6L-12Am, n, o, p, q, r, and t are each independently 0, 1, 2, 3, or 4;each ~ is independently a single bond or double bond;Ring A is selected from Ce-io aryl, 5-14 membered heterocycloalkyl, and 5-14 membered heteroaryl;each RAis independently selected from halo, Ci-6 alkyl, Ci-ealkylidenyl, C2-6 alkenyl, C2-6alkynyl, and C1-6 haloalkyl;LBis Ci-10 alkylene;Ring C2 is 4-7 membered heterocycloalkyl or 5-10 membered heteroaryl;Ring C7 is 4-14 membered heterocycloalkyl;Lcis selected from a bond and Ci-6 alkylene, wherein 1 or 2 methylene groups are each independently and optionally replaced by -C(O)-;54057-0036W01 / SNV0027-W01 PATENTeach RZ0is independently selected from Ci-6 alkyl, Ci.6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;each RB, Rc, RD, RE, and RFis independently selected from H, halo, C1-6 alkyl, C1-6 alkylidenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, -C(O)R, -C(O)NR2, and -C(O)NRNR2;each R is independently selected from H, C1-6 alkyl, 4-10 membered heterocycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, 4-10 membered heterocycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R° substituents;LBDis Ci-10 alkylene, wherein 1-6 methylene groups of the C1-10 alkylene are each independently and optionally replaced by -O- or -N(R)C(O)-;R10Aand R10Bare each H;R12Aand R12Bare each independently selected from H and 5-6 membered heteroaryl, wherein the 5-6 membered heteroaryl is optionally substituted with 1 or 2 R° substituents L is a bond or C1-20 alkylene, wherein 1-10 methylene groups of the C1-20 alkylene are each independently and optionally replaced by -Cy-, -NH-, -N(CH3)-, or -C(O)-;each Cy is independently selected from C3-10 cycloalkyl, Ce-io aryl, and 4-20 membered heterocycloalkyl, wherein the C3-10 cycloalkyl, Ce-io aryl, 4-20 membered heterocycloalkyl are each optionally substituted with 1 or 2 R° substituents;each R° is independently selected from H, halo, C1-6 alkyl, C1-6 alkylidenyl, C3-10 cycloalkyl, and -C(O)NRc0Rd0, wherein each C1-6 alkyl is optionally substituted with OH or CN; andeach Ra0, Rc0, and Rd0is independently selected from H and C1-6 alkyl.

56. The compound of any one of claims 1 to 3, wherein the compound is selected from:54057-0036W01 / SNV0027-W01 PATENT4-(4-( 1 -( 1 -(2,6-dioxopiperidin-3 -yl)-3 -methyl -2 -oxo-2, 3 -dihydro- 1H-benzo[d]imidazol-4-yl)piperidin-4-yl)-2-methoxyphenyl)-N, N-dimethyl-6-(2-methyl-3-oxo-1,2, 3, 5, 8, 8a-hexahydroimidazo[l,5-a]pyridin-6-yl)-lH-indole-2 -carboxamide;6-(3-(2-(lH-l,2,3-triazol-l-yl)ethyl)-5,8-dihydro-[l,2,4]triazolo[4,3-a]pyridin-6-yl)-4-(4-(4-(3-(l-(2, 6-dioxopiperidin-3-yl)-3 -methyl -2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-5-yl)propyl)piperazin- 1 -yl)phenyl)-N, N-dimethyl- lH-indole-2 -carboxamide;4-(4-(4-(2-( 1 -(2,6-dioxopiperidin-3 -yl)-3 -methyl -2 -oxo-2, 3 -dihydro- 1H-benzo[d]imidazol-4-yl)ethyl)piperazin- 1 -yl)-2-methoxyphenyl)-N, N-dimethyl-6-(2-methyl- 1 -oxo-2, 7 -diazaspiro [4.5] decan-7 -yl) - 1 H-indole -2 -carboxamide;6-(( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)pyrrolidin-2-yl)methyl)-4-(4-(4-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol-5 -yl)propyl)piperazin- 1 -yl)phenyl)-N, N-dimethyl- lH-indole-2 -carboxamide;6-( 1 -(3 -( IH-pyrazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -(2-( 1 -(2, 6 -dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-l,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[l,2-d][l,4]oxazin-8-yl)-N, N-dimethyl-lH-indole-2-carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -(4 -(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)-2,3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-N, N-dimethyl- 1 H-indole -2 -carboxamide;5 -( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-7 -(4-(4-(2-( l-(2, 6-dioxopiperidin-3-yl)-3 -methyl -2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-5-yl)ethyl)piperazin- 1 -yl)-2-methoxyphenyl)-N, N, 1 '-trimethylspiro[indene- 1,4'-piperidine]-2-carboxamide;5 -( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)- 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)piperidin-4-yl)-N, N-dimethylspiro[indene-l,4'-piperidine]-2 -carboxamide;3-(4-(2-(4-(4-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)- 1 '-methyl -2'-oxospiro [indoline-2,3 '-pyrrolidin] -4-yl)-3 -methoxyphenyl)piperazin- 1 -yl)ethyl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;1 '-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1 -(4-(4-(2-( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)piperazin-l-yl)-2-methoxyphenyl)-N, N-dimethyl-2-oxospiro[indoline-3,3'-piperidine]-6-carboxamide;6'-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)piperidin-3 -yl)- 1 -( 1 -(2-( 1 -(2, 6 -dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)piperidin-4-yl)-N, N-dimethyl-r,5',6',7'-tetrahydrospiro[piperidine-4,4'-pyrrolo[2,3-c]pyridine]-2'-carboxamide;54057-0036W01 / SNV0027-W01 PATENT7'-( 1 -(3 -( IH-pyrazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)- 1 -( 1 -(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)piperidin-4-yl)-N, N-dimethyl-r,3'-dihydrospiro[piperidine-4,5'-pyrano[3,4,5-cd]indole]-2'-carboxamide;2-( 1 -(3 -( IH-pyrazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-9-(4-(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)piperidin-l-yl)-N, N-dimethyl-7H-pyrrolo[3,2,l-de]phenanthridine-5-carboxamide;2-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-8-(l-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)-N, N-dimethyl-6,6a,7,8,9,10-hexahydro-4H-pyrazino[l,2-a]pyrrolo[4,3,2-de]quinoline-5-carboxamide;3-(5-(3-(4-(4-(7-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-2 -methyl- 1 -oxo-2, 3,4,9-tetrahydro- IH-pyrido [3,4-b] indol-5 -yl)phenyl)piperazin- 1 -yl)propyl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;8-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 11 -(4-(4-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-5-yl)propyl)piperazin-l-yl)phenyl)-N, N-dimethyl-3,5,5a,6,7,8,9,9a-octahydropyrido[3',4':4,5]pyrano[3,2-g]indole-2-carboxamide;5 -( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-9-(4-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)piperazin-l-yl)-N, N-dimethyl-3,7-dihydroisochromeno[4,3-e]indole-2-carboxamide;3-(4-(2-(4-(4-(9-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)- 10-fluoro-6, 11 -dihydro-5H-benzo [b]pyrido[3,2-f] azepin-7 -y 1) -3 -methoxyphenyl)piperazin- 1 -yl)ethyl)-3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol- 1 -yl)piperidine -2, 6-dione;3-(4-(2-(4-(14-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-8-methyl-9-oxo-6,7,8,9-tetrahydro-10,12-epiminodibenzo[h,j][l]oxa[4]azacycloundecin-3-yl)piperazin-l-yl)ethyl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2,6-dione;3-(4-(2-(4-(4-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-2-(4-methylenepiperidine- 1 -carbonyl)- lH-indol-4-yl)-3-methoxyphenyl)piperazin- 1 -yl)ethyl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione; and 3-(5-(3-(4-(4-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-3-((3,5-dimethyl-lH-pyrrol-2-yl)methylene)-2-oxoindolin-4-yl)phenyl)piperazin-l-yl)propyl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione; or a pharmaceutically acceptable salt thereof.54057-0036W01 / SNV0027-W01 PATENT57. The compound of claim any one of claims 1 to 3, wherein the compound is selected from:6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-l,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[l,2-d][l,4]oxazin-8-yl)-N, N-dimethyl-lH-indole-2-carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( l'-(2-( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)ethyl)-2,3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-l,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[l,2-d][l,4]oxazin-9-yl)-N, N-dimethyl-lH-indole-2-carboxamide;2-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-9-(4-(2-( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)ethyl)piperazin-l-yl)-N, N-dimethyl-7H-pyrrolo[3,2,l-de]phenanthridine-5-carboxamide;2-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-9-(4-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)piperazin-l-yl)-N, N-dimethyl-7H-pyrrolo[3,2,l-de]phenanthridine-5-carboxamide;2-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-8-(3-(l-(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)-N, N-dimethyl-6,6a,7,8,9,10-hexahydro-4H-pyrazino[l,2-a]pyrrolo[4,3,2-de]quinoline-5-carboxamide;2-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-8-(l-(3-(l-(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)piperidin-4-yl)-N, N-dimethyl-6,6a,7,8,9,10-hexahydro-4H-pyrazino[l,2-a]pyrrolo[4,3,2-de]quinoline-5-carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( l'-(2-( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)ethyl)-2,3 -dihydrospiro[indene-l,3'-pyrrolidin]-5-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)-2, 3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;3-(5-(3-(4-(4-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-T-methyl-2'-oxospiro[indoline-2,3'-pyrrolidin]-4-yl)phenyl)piperazin-l-yl)propyl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione; and54057-0036W01 / SNV0027-W01 PATENTll-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7-(4-(2-(l-(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)ethyl)piperazin-l-yl)-N, N-dimethyl-4,5-dihydrobenzo[4,5]azepino[3,2,l-hi]indole-2-carboxamide;or a pharmaceutically acceptable salt thereof.

58. The compound of claim 1, wherein the compound is selected from:6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -( 1 -( 3 -(2,6-dioxopiperidin-3-yl)-l-methyl-lH-indazol-7-yl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fhroro-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -(2 -( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fhroro-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -(4 -(2,6-dioxopiperidin-3-yl)-2-fluorophenethyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro -N, N -dimethyl- 1 H-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -( 1 -(4 -(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fhroro-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -(2 -( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-lH-indazol-4-yl)ethyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fhroro-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fhroro-N, N-dimethyl-lH-indole-2-carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -(2 -( 3 -(2,6-dioxopiperidin-3 -yl)- 1 -methyl- lH-indazol-7 -yl)ethyl)-3H-spiro [isobenzofuran- 1,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2-carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-lH-indazol-4-yl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;54057-0036W01 / SNV0027-W01 PATENT6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-( 1 -(3 -(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)- 1 -methyl-lH-indazol-6-yl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)azetidin-3 -yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2-carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -( 1 -(4 -chloro-3-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)benzoyl)azetidin-3-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -( 1 -(4 -chloro-3-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)benzoyl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;3-(5-(4-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7 -fluoro-2-(3 -methyleneazetidine- 1 -carbonyl)- lH-indol-4-yl)-3H-spiro[isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol- 1 -yl)piperidine -2, 6-dione;3-(4-(4-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7 -fluoro-2-(3 -methyleneazetidine- 1 -carbonyl)- lH-indol-4-yl)-3H-spiro[isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -fluorophenyl)piperidine-2, 6-dione;l-(6-(4-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7 -fluoro-2-(3 -methyleneazetidine- 1 -carbonyl)- lH-indol-4-yl)-3H-spiro[isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1-yl)- 1 -methyl- lH-indazol-3-yl)dihydropyrimidine-2,4( 1H,3H)-dione;3-(6-(4-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7 -fluoro-2-(3 -methyleneazetidine- 1 -carbonyl)- lH-indol-4-yl)-3H-spiro[isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -yl)- 1 -methyl- lH-indazol-3 -yl)piperidine-2, 6-dione;3-(4-(4-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7 -fluoro-2-(3 -methyleneazetidine- 1 -carbonyl)- lH-indol-4-yl)-3H-spiro[isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol- 1 -yl)piperidine -2, 6-dione;3-(4-(3-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7 -fluoro-2-(3 -methyleneazetidine- 1 -carbonyl)- lH-indol-4-yl)-3H-spiro[isobenzofuran- 1,4'-piperidin] - 1 '-yl)azetidin- 1 -yl)-3-methyl-2-oxo-2,3-dihydro- lH-benzo[d]imidazol- 1 -yl)piperidine -2, 6-dione;54057-0036W01 / SNV0027-W01 PATENT3-(4-(2-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-2-(3-methyleneazetidine-l-carbonyl)-lH-indol-4-yl)-2,3-dihydrospiro[indene-l,4'-piperidin] - 1 '-yl)ethyl)-3-methyl-2-oxo-2,3-dihydro- lH-benzo[d]imidazol- 1 -yl)piperidine-2,6-dione;3-(4-(4-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-2-(3-methyleneazetidine-l-carbonyl)-lH-indol-4-yl)-2,3-dihydrospiro[indene-l,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol- 1 -yl)piperidine -2, 6-dione;l-(6-(4-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7 -fluoro-2-(3 -methyleneazetidine- 1 -carbonyl)- lH-indol-4-yl)-3H-spiro[isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1-yl)- 1 -methyl- lH-indazol-3-yl)dihydropyrimidine-2,4( 1H,3H)-dione;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -( 1 -(4 -(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)-6-fluoro-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -(2 -( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -(2 -( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-l-methyl-2-oxospiro[indoline-3,4'-piperidin]-6-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -(2 -( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-l-methylspiro[indoline-3,4'-piperidin]-6-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)-2-methyl-3-oxospiro[isoindoline-l,4'-piperidin]-5-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( l'-(2-( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)ethyl)-3 -oxo-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)-2-methylspiro[isoindoline-l,4'-piperidin]-5-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)-54057-0036W01 / SNV0027-W01 PATENT3.3-dimethyl-2-(methylimino)-2-oxido-2,3-dihydro-216-spiro[benzo[c]thiophene-l,4'-piperidin] -5 -yl) -N, N -dimethyl- 1 H-indole -2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 ' -(2 -( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-2H-spiro [benzofuran-3,4'-piperidin]-6-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;6-(5-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-5-azaspiro[3.5]non-7-en-7-yl)-4-(l'-(3-(l-(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)- 2.3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;6-((lS,5R)-8-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-8-azabicyclo[3.2.1]oct-2-en-2-yl)-4-(l'-(3-(l-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-5-yl)propyl)-2,3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-N, N-dimethyl-lH-indole-2-carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenethyl)-l,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[l,2-d][l,4]oxazin-8-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-lH-indazol-4-yl)ethyl)-l,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[ 1,2-d] [ 1,4]oxazin-8-yl)-N, N-dimethyl- lH-indole-2-carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -( 1 -(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)-l,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[ 1,2-d] [ 1,4]oxazin-8-yl)-N, N-dimethyl- lH-indole-2-carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)piperidin-4-yl)-l,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[l,2-d][l,4]oxazin-8-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -( 1 -(3 -(2,6-dioxopiperidin-3 -yl)- 1 -methyl- lH-indazol-6-yl)piperidin-4-yl)- 1,2,3,4,4a, 5 -hexahydrobenzo[b]pyrazino[ 1,2-d] [ 1,4]oxazin-8-yl)-N, N-dimethyl- lH-indole-2-carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( l'-(4-( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)cyclohexyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;54057-0036W01 / SNV0027-W01 PATENT6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-(( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)piperidin-4-yl)methyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2-carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)azetidine-3 -carbonyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2-carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)pyrrolidine- 3-carbonyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2-carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)piperidine- 4-carbonyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2-carboxamide;3-(5-(4-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-2-(3-methyleneazetidine-l-carbonyl)-lH-indol-4-yl)-2, 3-dihydrospiro[indene-l, d'piperidine] - 1 '-carbonyl)piperidin- 1 -yl)-3 -methyl -2 -oxo-2, 3 -dihydro- lH-benzo[d]imidazol- 1 -yl)piperidine -2, 6-dione;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-2,3,4,4a,5,6-hexahydro-lH-benzo[b]pyrazino[l,2-d][l,4]oxazepin-9-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-l,2,3,4,4a,5-hexahydro-7H-benzo[e]pyrazino[2,l-c][l,4]oxazepin-9-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-6-methyl-5-oxo-2,3,4,4a,5,6-hexahydro-lH-pyrazino[l,2-a]quinoxalin-8-yl)-7-fluoro-N, N-dimethyl- 1 H-indole -2-carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -(2-( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)ethyl)-7 -methyl-6-oxo-l,2,3,4,4a,5,6,7-octahydrobenzo[b]pyrazino[l,2-d][l,4]diazepin-9-yl)-7-fluoro-N, N -dimethyl- 1 H-indole -2-carboxamide;54057-0036W01 / SNV0027-W01 PATENT6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-(3 -(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-6-methyl-2,3,4,4a,5,6-hexahydro-lH-pyrazino[l,2-a]quinoxalin-8-yl)-7-fluoro-N, N-dimethyl-1 H-indole -2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)-2,3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-7-fluoro-N, N', N'-trimethyl-lH-indole-2-carbohydrazide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( l'-(2-( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)ethyl)-2,3 -dihydrospiro[indene-l,4'-piperidin]-5-yl)-7-fluoro-N-methyl-N-((6-(methylcarbamoyl)pyridin-3-yl)methyl)-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)-2,3 -dihydrospiro [indene- 1,4'-piperidin] -5 -yl)-7 -fluoro-N-(2-( 1 -(hydroxymethyl)cyclopropyl)ethyl)-N-methyl-lH-indole-2 -carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)azetidine-3 -carbonyl)-2,3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-7-fluoro-N-methyl-N-(2-(6-(methylcarbamoyl)pyridin-3 -yl)ethyl) - 1 H-indole -2 -carboxamide;6-( 1 -(3-( 1H- 1,2,3-triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3-yl)-N-(2-( 1 -(cyanomethyl)piperidin-4-yl)ethyl)-4-(r-(3-(l-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro- IH-benzo [d]imidazol-5 -yl)propyl)-2, 3 -dihydrospiro [indene- 1,4'-piperidin] -5 -yl)-7 -fluoro -N -methyl - 1 H-indole-2 -carboxamide;6-( 1 -(3-( 1H- 1,2,3-triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3-yl)-N-(2-( 1 -(2-cyanoethyl)piperidin-4-yl)ethyl)-4-(r-(3-(l-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro- IH-benzo [d]imidazol-5 -yl)propyl)-2, 3 -dihydrospiro [indene- 1,4'-piperidin] -5 -yl)-7 -fluoro -N -methyl - 1 H-indole-2 -carboxamide;6-( 1 -(3-( 1H- 1,2,3-triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3-yl)-N-(2-( 1 -cyclopropylpiperidin-4-yl)ethyl)-4-(r-(3-(l-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro- IH-benzo [d]imidazol-5 -yl)propyl)-2, 3 -dihydrospiro [indene- 1,4'-piperidin] -5 -yl)-7 -fluoro -N -methyl - 1 H-indole-2 -carboxamide;3-(5-(3-(5-(6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-2-(3-(propan-2-ylidene)azetidine-l-carbonyl)-lH-indol-4-yl)-2,3-dihydrospiro| indene- 1,4'-piperidin]- 1 '-yl)propyl)-3-methyl-2-oxo-2,3-dihydro- 1H-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;54057-0036W01 / SNV0027-W01 PATENT5 -( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-7 -( 1 '-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)-2,3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-4-fluoro-N, N-dimethylbenzofuran-2-carboxamide;2-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-8-(4-(2-(l-(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-4-yl)ethyl)piperazin-l-yl)-3-fluoro-N, N-dimethyl-4,6-dihydronaphtho[3,2,l-cd]indole-5-carboxamide;3-(4-(2-(5-(7-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)- 8-fluoro-2-methyl-l-oxo-2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indol-5-yl)-2,3-dihydrospiro[indene- 1,4'-piperidin]- 1 '-yl)ethyl)-3-methyl-2-oxo-2,3-dihydro- 1H-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(4-(2-(4-(4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,2,3,4,5,10-hexahydroazepino[3,4-6]indol-6-yl)phenyl)piperazin- 1 -yl)ethyl)-3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol- 1 -yl)piperidine -2, 6-dione;3-(4-(2-(8-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)- 9-fluoro-2-methyl-l-oxo-l,2,3,4,5,10-hexahydroazepino[3,4-b]indol-6-yl)-l,2,4a,5-tetrahydrobenzo[b]pyrazino[l,2-d][l,4]oxazin-3(4H)-yl)ethyl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(4-(2-(5-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,2,3,4,5,10-hexahydroazepino[3,4-b]indol-6-yl)-3H-spiro [isobenzofuran- 1, 4'-piperidin]-T-yl)ethyl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(4-(2-(4-(4-(9-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-10-fluoro-2-methyl-l-oxo-2,3,4,5,6,l l-hexahydro-lH-azocino[3,4-6]indol-7-yl)phenyl)piperazin- 1 -yl)ethyl)-3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [ d\ i m idazol - 1 -yl)piperidine -2, 6-dione;3-(4-(2-(4-(4-(7'-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-2'-methyl-r-oxo-r,2',4',9'-tetrahydrospiro[cyclopropane-l,3'-pyrido[3,4-6]indol]-5'-yl)phenyl)piperazin- 1 -yl)ethyl)-3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [ d\ i m idazol - 1 -yl)piperidine -2, 6-dione;2-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)-7 -(4-(4-(2-( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)piperazin-l-yl)phenyl)-H, H-dimethyl-l,2,3,4,5,10-hexahydropyrido[3',4':4,5]pyrano[2,3- / |indole-9-carboxamide;54057-0036W01 / SNV0027-W01 PATENT3-(5-(3-(5-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-cyclopropan] -6-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)propyl)-3 -methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-(3-(5-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-cyclopropan] -6-yl)-3H-spiro [isobenzofuran- 1,4'-piperidine] - 1 '-carbonyl)azetidin- 1 -y 1) -3 -methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;6-(6-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-6-azaspiro[3.5]non-8-en-8-yl)-4-(l'-(3-(l-(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2-carboxamide;6-(6-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-6-azaspiro[3.5]non-8-en-8-yl)-4-(l'-(l-(l-(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fhroro-N, N-dimethyl-lH-indole-2-carboxamide;6-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2-dihydroquinolin-3 -yl)-4-( 1 '-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol-5 -yl)propyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fhroro-N, N-dimethyl-lH-indole-2 -carboxamide;6-(9-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)-9-azabicyclo [4.2.1 ]non-2-en-2-yl)-4-( 1 ' -(3 -(l-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-5-yl)propyl)-2, 3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-N, N-dimethyl-lH-indole-2 -carboxamide;6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-2,4a,5,6,7,7a-hexahydro-lH-cyclopenta[b]pyridin-3-yl)-4-( l'-(3-( l-(2, 6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-5-yl)propyl)-2,3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-N, N-dimethyl- 1 H-indole -2 -carboxamide;6-(6-(3-( 1H- 1,2,3-triazol- 1 -yl)propanoyl)-6-azaspiro[3,5]nonan-8-yl)-4-( 1 '-(3 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)propyl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fhroro-N, N-dimethyl-lH-indole-2-carboxamide;6-( 1 -(3 -( 1H- 1,2,3-triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-4-( 1 "-( 1 -(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)-r,2',5',6',8',8a'-hexahydro-3H-dispiro[isobenzofuran-l,7'-indolizine-3',4"-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide; and6-( 1 -(3-( 1H- 1,2,3-triazol- 1 -yl)propanoyl)- 1,2,5, 6-tetrahydropyridin-3-yl)-4-( 1 "-(2-( 1 -(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)ethyl)-54057-0036W01 / SNV0027-W01 PATENTT,2',5',6',8',8a'-hexahydro-3H-dispiro[isobenzofuran-l,7'-indolizine-3',4"-piperidin]-5-yl)-7-fluoro -N, N -dimethyl- 1 H-indole-2 -carboxamide;or a pharmaceutically acceptable salt thereof.

59. The compound of claim 1, which is selected from:3-(5-(4-((4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-cyclopropan]-6-yl)-2,5-difluorobenzyl)amino)piperidin-l-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-(4-(4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3, T-cyclopropan]-6-yl)-2, 5-difluorobenzyl)piperazin-l-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-(4-(4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fhroro-2 -methyl- 1 -oxo- 1,4,5, 10-tetrahydro-2H-spiro [azepino [3,4-b] indole-3, T-cyclopropan]-6-yl)-2, 5-difluorophenyl)-[l,4'-bipiperidin]-T-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-(4-(5-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-cyclopropan] -6-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl -2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(6-(4-(5-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-cyclopropan] -6-yl)-3H-spiro[isobenzofuran- 1,4'-piperidin]- 1 '-yl)piperidin- 1 -yl)- 1 -methyl- 1H-indazol-3-yl)piperidine-2, 6-dione;3-(5-(4-(5-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3, T-cyclopropan] -6-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl -2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-(4-(4-(4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-cyclopropan] -6-yl)phenyl)piperazin- 1 -yl)piperidin- 1 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-(4-(4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-54057-0036W01 / SNV0027-W01 PATENTcyclopropan]-6-yl)-2, 3-difluorophenyl)-[l,4'-bipiperidin]-T-yl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-((4-(4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4,l'-cyclopropan] -6-yl)phenyl)piperazin- 1 -yl)methyl)-3 -methyl -2 -oxo-2, 3 -dihydro- 1H-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-(4-(8-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-cyclopropan] -6-yl)- 1,2,4a,5-tetrahydrobenzo[b]pyrazino[ 1,2-d] [ 1,4]oxazin-3(4H)-yl)piperidin-l-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2,6-dione;3-(5-(4-(5-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3, T-cyclopropan] -6-yl)-2, 3 -dihydrospiro [indene- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-(4-(4-(4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3, T-cyclopropan] -6-yl)-2,3 -difluorophenyl)piperazin- 1 -yl)piperidin- 1 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-((4-(4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3, T-cyclopropan]-6-yl)-2,3-difluorophenyl)piperazin-l-yl)methyl)-3-methyl-2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-(4-(5-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3, T-cyclopropan] -6-yl)-6-methoxy-3H-spiro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-(4-(4-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3, T-cyclopropan] -6-yl)piperazin- 1 -yl)piperidin- 1 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1H-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-(4-(8-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3, T-cyclopropan]-6-yl)-2,8-diazaspiro[4.5]decan-2-yl)piperidin-l-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;54057-0036W01 / SNV0027-W01 PATENT5-(2-(dimethylcarbamoyl)-7-fluoro-6-(pyridin-3-yl)-lH-indol-4-yl)-N, N-dimethyl-3H-spiro [isobenzofuran- 1,4'-piperidine] - 1 '-carboxamide;6-(9-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-3-oxa-9-azabicyclo[3.3.1]non-6-en-6-yl)-4-( l'-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol-5 -yl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;6-(7-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-2-oxa-7-azaspiro[4.5]dec-9-en-9-yl)-4-(l'-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol-5 -yl)piperidin-4-yl)-3H-spiro[isobenzofuran-l,4'-piperidin]-5-yl)-7-fluoro-N, N-dimethyl-lH-indole-2 -carboxamide;6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-2,4a,5,6,7,7a-hexahydro-lH-cyclopenta[b]pyridin-3-yl)-4-( l'-(l-( l-(2, 6-dioxopiperidin-3-yl)-3-methyl-2 -oxo-2, 3-dihydro-IH-benzo [d]imidazol-5 -yl)piperidin-4-yl)-2, 3 -dihydrospiro [indene- 1,4'-piperidin] -5 -yl)-7 -fluoro -N, N -dimethyl- 1 H-indole-2 -carboxamide;6-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,4a,5,7,7a-hexahydrofuro[3,4-b]pyridin-3 -yl)-4-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol-5 -yl)piperidin-4-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] -5 -yl)-7 -fluoro-N, N -dimethyl- 1 H-indole -2 -carboxamide;3-(5-(4-(5-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-cyclopropan] -6-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -yl)-4-fluoro-3 -methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-(4-(8-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4, T-cyclopropan] -6-yl)- 1,2,4a,5-tetrahydrobenzo[b]pyrazino[ 1,2-d] [ 1,4]oxazin-3(4H)-yl)piperidin- 1 -yl)-4-fluoro-3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d]imidazol- 1 -yl)piperidine -2, 6-dione;l-(5-(7-fluoro-4-(2-methoxyphenyl)-2-(3-methyleneazetidine-l-carbonyl)-lH-indol-6-yl)-3,6-dihydropyridin- 1 (2H)-yl)-3 -( 1H- 1,2,3 -triazol- 1 -yl)propan- 1 -one;1 -(5 -(4-( 1 '-acetyl-3H-spiro [isobenzofuran- 1,4'-piperidin] -5 -yl)-7 -fluoro-2-(3 -methyleneazetidine- 1 -carbonyl)- lH-indol-6-yl)-3,6-dihydropyridin- 1 (2H)-yl)-3 -( 1H- 1,2,3 -triazol - 1 -yl)propan- 1 -one;3 -(5 -(4-(8-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-9-fluoro-2-methyl-l-oxo-2,3,5,10-tetrahydro-lH-spiro[azepino[3,4-b]indole-4,r-cyclopropan]-6-yl)-2 -fluoro-5-methoxyphenyl)-3 -methyl -2 -oxo-2, 3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine -2, 6-dione;54057-0036W01 / SNV0027-W01 PATENT3-(5-(4-((l-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3,l'-cyclopropan]-6-yl)piperidin-4-yl)methyl)piperazin-l-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-(l-((l-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3,l'-cyclopropan]-6-yl)piperidin-4-yl)methyl)piperidin-4-yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-(4-(l-(8-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3, T-cyclopropan] -6-yl)piperidin-4-yl)piperazin- 1 -yl)-3-methyl-2-oxo-2,3-dihydro- 1H-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-(4-(5-(7'-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-8'-fluoro-2'-methyl-r-oxo-r,2',4,4',5,9'-hexahydro-2H-spiro[furan-3,3'-pyrido[3,4-b]indol]-5 '-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl-2-oxo-2,3 -dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-(4-(5-(7'-(l-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-8'-fluoro-2'-methyl-l'-oxo-l',2,2',3,4',5,6,9'-octahydrospiro[pyran-4,3'-pyrido[3,4-b]indol]-5'-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl-2-oxo-2,3 -dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-(4-(5-(7'-(6-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-6-azaspiro[3.5]non-8-en-8-yl)-8'-fluoro-2'-methyl-l'-oxo-l',2',4',9'-tetrahydrospiro[cyclopropane-l,3'-pyrido[3,4-b]indol]-5'-yl)-2, 3 -dihydrospiro [indene- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl-2-oxo-2,3 -dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3 -(5 -(4-(5 -(8-( 1 -(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)-5,5 -dimethyl- 1,2,5,6-tetrahydropyridin-3 -yl)-9-fluoro-2 -methyl- 1 -oxo- 1,4,5, 10-tetrahydro-2H-spiro [azepino [3,4-b] indole-3, 1 '-cyclopropan] -6-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-(4-(5-(8-(6-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-6-azaspiro[3.5]non-8-en-8-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3,r-cyclopropan] -6-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl -2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;3-(5-(4-(5-(8-(6-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-6-azaspiro[3.5]non-8-en-8-yl)-9-fluoro-2-methyl-l-oxo-l,4,5,10-tetrahydro-2H-spiro[azepino[3,4-b]indole-3,r-cyclopropan] -6-yl)-2, 3 -dihydrospiro [indene- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -yl)-3-methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-l-yl)piperidine-2, 6-dione;54057-0036W01 / SNV0027-W01 PATENT2-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)-7 -( l'-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)piperidin-4-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] -5 -yl)-N, N-dimethyl- 1,2,3,4, 4a, 5, 10, 11b-octahydropyrido[3',4':4,5]pyrano[2,3-f]indole-9-carboxamide;2-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)-7 -(2-methoxyphenyl)-N, N-dimethyl-l,2,3,4,4a,5,10,llb-octahydropyrido[3',4':4,5]pyrano[2,3-f]indole-9-carboxamide;2-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)-7 -( l'-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)piperidin-4-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] -5 -yl)- 11 -fluoro-N, N-dimethyl- 1, 2, 3, 4, 4a, 5, 10, 11b-octahydropyrido[3',4':4,5]pyrano[2,3-f]indole-9-carboxamide;2-(3 -( 1H- 1,2,3 -Triazol- 1 -yl)propanoyl)-7 -(4-(4-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-5-yl)piperidin-4-yl)piperazin-l-yl)phenyl)-N, N-dimethyl-l,2,3,4,4a,5,10,llb-octahydropyrido[3',4':4,5]pyrano[2,3-f]indole-9-carboxamide;2-Acetyl-7 -(4-( l'-( 1 -(2,6-dioxopiperidin-3 -yl)-3 -methyl-2-oxo-2,3-dihydro-lH-benzo[d]imidazol-5-yl)-[l,4'-bipiperidin]-4-yl)phenyl)-N, N-dimethyl-l,2,3,4,4a,5,10,llb-octahydropyrido[3',4':4,5]pyrano[2,3-f]indole-9-carboxamide;2-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)-8-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)piperidin-4-yl)-3H-spiro [isobenzofuran- 1,4'-piperidin] -5 -yl)-N, N-dimethyl- 1,2,3,4,6,7, 11, 12b-octahydropyrazino [2, 1 -a]pyrrolo [3,2-g] isoquinoline- 10-carboxamide;2-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)-7 -(2-methoxyphenyl)-N, N-dimethyl-l,2,3,4,4a,5,10,llb-octahydropyrido[3',4':4,5]pyrano[2,3-f]indole-9-carboxamide;2-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)- 11 -fluoro-7 -(2-methoxyphenyl)-N, N-dimethyl-l,2,3,4,4a,5, 10, 1 lb-octahydropyrido[3',4':4,5]pyrano[2,3-f]indole-9-carboxamide;2-(3-( 1H- 1,2,3-triazol- 1 -yl)propanoyl)-8-(2-methoxyphenyl)-N, N-dimethyl-l,2,3,4,6,7,ll,12b-octahydropyrazino[2,l-a]pyrrolo[3,2-g]isoquinoline-10-carboxamide;6-(6-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-6-azaspiro[3.5]non-8-en-8-yl)-7-fluoro-4-(2-methoxyphenyl) -N, N -dimethyl- 1 H-indole -2 -carboxamide;7'-(6-(3-(lH-l,2,3-triazol-l-yl)propanoyl)-6-azaspiro[3.5]non-8-en-8-yl)-8'-fluoro-5'-(2-methoxyphenyl)-2'-methyl-4',9'-dihydrospiro[cyclopropane-l,3'-pyrido[3,4-b]indol]-T(2'H)-one;2-(3 -( 1H- 1,2,3-triazol- 1 -yl)propanoyl)- 12-fluoro-8-(2-methoxyphenyl)-N, N-dimethyl-l,2,3,4,6,7,ll,12b-octahydropyrazino[2,l-a]pyrrolo[3,2-g]isoquinoline-10-carboxamide;54057-0036W01 / SNV0027-W01 PATENT2-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)-8-( 1 '-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- IH-benzo [d] imidazol-5 -yl)piperidin-4-yl)-2,3-dihydrospiro[indene-l,4'-piperidin]-5-yl)-12-fluoro-N, N-dimethyl-l,2,3,4,6,7,ll,12b-octahydropyrazino [2, 1 -a]pyrrolo [3,2-g] isoquinoline- 1 O-carboxamide;2-(3 -( 1H- 1,2,3 -triazol- 1 -yl)propanoyl)-7 -(4-(4-( 1 -( 1 -(2,6-dioxopiperidin-3 -y 1) -3 -methyl -2 -oxo-2, 3 -dihydro- 1 / / -benzo [d] imidazol-5 -yl)piperidin-4-yl)piperazin- 1 -yl)phenyl)-ll-fluoro- / V, / V-dimethyl-l,2,3,4,4a,5,10,llb-octahydropyrido[3',4':4,5]pyrano[2,3- |indole-9-carboxamide;2-(3 -( I / / - 1,2,3 -triazol- 1 -yl)propanoyl)- 11 -fluoro-7 -(2-mcthoxy phen l )- '. A-dimethyl-l,2,3,4,4a,5, 10, 1 lb-octahydropyrido[3',4':4,5]pyrano[2,3- / |indole-9-carboxamide;3 -(5 -(4-(5 -(9'-( 1 -(3 -( 1 / V- 1,2,3 -triazol- 1 -yl)propanoyl)- 1,2,5,6-tetrahydropyridin-3 -yl)-10'-fluoro-2'-methyl-T-oxo-T,2',4',5'-tetrahydrospiro[cyclopropane-l,3'-[l,4]diazepino[l,2-a] indol] -7'-yl)-32 / -spiro [isobenzofuran- 1,4'-piperidin] - 1 '-yl)piperidin- 1 -y 1) -3 -methyl-2-oxo-2.3-dihydro-l / / -bcnzo|d|imidazol-l-yl)pipcridinc-2.6-dione; and9'-(l-(3-(12 / -l,2,3-triazol-l-yl)propanoyl)-l,2,5,6-tetrahydropyridin-3-yl)-10'-fluoro-7'-(2-methoxyphenyl)-2'-methyl-4',5'-dihydrospiro[cyclopropane-l,3'-[l,4]diazepino[l,2-a] indol] - 1 '(2 / )-one;or a pharmaceutically acceptable salt thereof.

60. A pharmaceutical composition, comprising a compound of any one of claims 1 to 59, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

61. A method of inhibiting an activity of STAT6, comprising contacting the STAT6 with a compound of any one of claims 1 to 59, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

62. A method of treating a STAT6-mediated disease or disorder in a patient, comprising administering to the patient a therapeutically effective amount of a compound of any one of claims 1 to 59, or a pharmaceutically acceptable salt thereof.

63. The method of claim 62, wherein the disease or disorder is selected from an allergic inflammatory disease, a chronic inflammatory disease, an autoimmune disease, and cancer.

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