Benzamide ARYL ether analogs comprising a 4,5-spiro ring system as inhibitors of the menin-MLL interaction

Abstract

The present disclosure is directed to benzamide amine aryl ether analogs comprising a 4,5-spiro ring system of Formula I, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, as inhibitors of the interaction of menin with MLL and MLL fusion proteins, pharmaceutical compositions containing the same, and their use in the treatment of cancer and other diseases mediated by the menin-MLL interaction.

Description

[0001] 43707-02999 / WO (SYND-070 / 001WO)

[0002] BENZAMIDE ARYL ETHER ANALOGS COMPRISING A 4,5-SPIRO RING SYSTEM AS INHIBITORS OF THE MENIN-MLL INTERACTION

[0003] RELATED APPLICATIONS

[0004] This application claims the benefit of and priority to U. S. Provisional Application No.

[0005] 63 / 764,044, filed February' 27, 2025, and U. S. Provisional Application No. 63 / 950,335, filed December 29, 2025, the contents of each which are incorporated herein by reference in their entireties.

[0006] BACKGROUND

[0007] The mixed-lineage leukemia (MLL), also known as KMT2A, gene encodes a protein that is a histone methyltransferase that is mutated in clinically and biologically distinctive subsets of acute leukemia. Rearranged mixed lineage leukemia (MLL-r) involves recurrent translocations of the Hq23 chromosome locus which lead to an aggressive form of acute leukemia with limited therapeutic options. These translocations target the MLL gene creating an oncogenic fusion protein comprising the amino-terminus of MLL fused in frame with more than 60 different fusion protein partners. Menin, a ubiquitously expressed, nuclear protein encoded by the multiple endocrine neoplasia type 1 (MEN I) tumor suppressor gene, has a high affinity binding interaction with MLL fusion proteins and is an essential co-factor of oncogenic MLL-r fusion proteins. Disruption of this interaction leads to selective growth inhibition and apoptosis of MLL-r leukemia cells both in vitro and in vivo.

[0008] The interaction between menin and MLL or MLL fusion proteins is an attractive target for therapeutic intervention, and there is a need for novel agents that inhibit the menin-MLL interaction for the treatment of various diseases and conditions, including leukemia, other cancers, and diabetes.

[0009] SUMMARY

[0010] In one aspect, the present disclosure is directed to a compound of Formula L

[0011]

[0012] I43707-02999 / WO (SYND-070 / 001WO)

[0013] a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0014] V is N or CH;

[0015] Y is N or CH;

[0016] e

[0017]

[0018] Cy is, wherein e and f indicate points of attachment to the remainder of the molecule;

[0019] is

[0020] (a) C 1-6 haloalky 1, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, 5- to 10- membered heteroaryl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -63-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Cj-6 alkyl, or -(4- to 10-membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-ioaryl, 5- to 10-membered heteroaryl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, -Co-io aryl-Ci-6 alkyl, -63-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl )-C 1-6 alkyl, and -(4- to 10-membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0021] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0022] each Rlsis independently oxo or =NR4a;

[0023] (c) -Ci-6 alkylene-N(R3a’)(R3b’ ) or -63-12 cycloalkylene-N(R3a’)(R3b’ ), wherein the C1-6 alkylene or 63-12 cycloalkylene is optionally substituted with one or more

[0024] each Rlasis independently halo, oxo, 61-6 alkyl, 61-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(===O)2R3a’;

[0025] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;43707-02999 / WO (SYND-070 / 001WO)

[0026] each Rlbsis independently halo, oxo, OR3a’, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(:::O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[0027] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0028] each Rlcsis independently halo, oxo, Ci-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the Ci-6 alkyl or Cj-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0029] each R3a’ is independently H, C1-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-e alkoxy;

[0030] each R3b’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0031] each R3C’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl;

[0032] R2is H, Ci-6 alkyl, Cue haloalkyl, Cj-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, -Ce-ioaryl-C1-6 alkyl, -C3-i2cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, or -(3- to 12-membered heterocycloalkyl)-Ci-6 alkyl, wherein said Ci-6 alkyl, C 1-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-ioaryl, C3-12 cycloalkyl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, -C6-10 aryl-Cj-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, and -(3- to 12-membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or

[0033] R1and R2form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;

[0034] each Rsis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Cb-10 aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-6 cycloalkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, cyano-C ns alkyl, HO-C1-3 alkyl, amino, Ci-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, Ci-6 alkylsulfinyl, Ci-6 alkylsulfonyl, carboxy, aminocarbonyl, Ci-6 alkyl carbonyl, and Ci-6 alkoxy carbonyl;43707-02999 / WO (SYND-070 / 001WO)

[0035] Ring A is 6- to 10-membered aryl or 5- to 10-membered heteroaryl, wherein the 6- to 10-membered aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;

[0036] X3is H or Cj-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0037] when m is 0:

[0038] RJis Ci-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, wherein the C 1-6 alkyl, C2-6 alkenyl, or C2-6 al ynyl is optionally substituted with one or more R3as;

[0039] each Rjasis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(==O)2R4b’, or N(R4a)(R4b);

[0040] when m is 1:

[0041] R3is H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cj-6 alkoxy, C3-12 cycloalkyl, Cs-10 aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3- 12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a, or

[0042] R3forms a 3- to 12-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[0043] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), O

[0044]

[0045] C(O)N(R4a)(R4b), S(===O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[0046] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[0047] each R4bis independently H

[0048]

[0049] , S(==O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’);43707-02999 / WO (SYND-070 / 001WO)

[0050] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0051] each RNIS independently H, C1-6 alkyl, or C1-6 haloalkyl;

[0052] m is 0 or 1; and

[0053] n is 1, 2, or 3;

[0054] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0055] In one aspect, the present disclosure is directed to a compound of Formula II:

[0056]

[0057] Formula II, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0058] V is N or CH;

[0059] Y is N or CH;

[0060] R1is

[0061] (a) C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, 5- to 10- membered heteroaryl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -63-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Cj-6 alkyl, or -(4- to 10-membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, CYioaryl, 5- to 10-membered heteroaryl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, -Cg-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, and -(4- to 10-membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0062] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0063] each Rlsis independently oxo or =NR4a;43707-02999 / WO (SYND-070 / 001WO)

[0064] (c) -Ci-6 alkylene-N(R3a,)(R3b’) or -C3-12 cycloalkylene-N(R3a,)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rias;

[0065] each Riasis independently halo, oxo, Cj-6 alkyl, C1-6 haloalkyl, C(:::O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0066] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12 -membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0067] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(-O)2R3a’; or

[0068] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0069] each Rlcsis independently halo, oxo, C1-6 alkyl, Cj-6 haloalkyl, C(=O)(R3a’), N

[0070]

[0071] (R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0072] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, Cj-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0073] each R31” is independently H, Ci-e alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0074] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl;

[0075] R2is H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl,

[0076]

[0077] 12 cycloalkyl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, -Ce-ioaryl-C1-6 alkyl, -C3-i2cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, or -(3- to 12-membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, Ci-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, -C6-ioaryl-C]-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, and -(3- to 12-membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rs; or43707-02999 / WO (SYND-070 / 001WO)

[0078] R1and R2form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;

[0079] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-6 cycloalkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, Ci-6 alkylamino, di(Ci- alkyl'Jamino, thiol, C 1-6 alkylthio, Cj-6 alkylsulfinyl, Ci-6 alkylsulfonyl, carboxy, aminocarbonyl, C 1-6 alkylcarbonyl, and Ci-6 alkoxy carbonyl;

[0080] R3is Cj-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, wherein the Ci-6 alkyl, C2-6 alkenyl, or C2- 6 alkynyl is optionally substituted with one or more R3as;

[0081] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, or N(R4a)(R4b);

[0082] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[0083] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, Cs-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Cj-6 alkoxy or C(O)N(R4a’)(R4b’);

[0084] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0085] each RNIS independently H, Ci-6 alkyl, or Ci-6 haloalkyl;

[0086] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0087] In one aspect, the present disclosure is directed to a compound of Formula III:

[0088]

[0089] N Formula I II a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:43707-02999 / WO (SYND-070 / 001WO)

[0090] R1is C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0091] each Rlcsis independently halo, oxo, Ci-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(Rjb’), OR3a’, or S(=O)2Rja’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more Ci-6 alkoxy;

[0092] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0093] each R3b’ is independently H, Ct-6 alkyl, Cj-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0094] each R3C’ is independently H, Cj-6 alkyl, C1-6 haloalkyl, €3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0095] R2is H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, -Ch-ioaryl-C1-6 alkyl, -C3-12 cycloalkyl-C 1-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, or -(3- to 12-membered heterocycloalkyl)-Ci-6 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -63-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, and -(3- to 12-membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from R8;

[0096] each Rsis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, Ch-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C 1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyd, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C1-6 alkylthio, C1-6 alkylsulfinyl, Cj-6 alkylsulfonyl, carboxy, aminocarbonyl, C 1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[0097] R3is Ct-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, wherein the Cj-6 alkyl, C2-6 alkenyl, or C2- 6 alkynyl is optionally substituted with one or more R3as;

[0098] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, or N(R4a)(R4b);

[0099] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);43707-02999 / WO (SYND-070 / 001WO)

[0100] each R4bis independently H, S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, Ca-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);

[0101] each R4a’ and R4b?is independently H, Ci-6 alkyl, Cs-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0102] each RNIS independently H, Ci-6 alkyl, or Ci-6 haloalkyl.

[0103] In one aspect, the present application relates to a pharmaceutical composition comprising a compound of the application, or a pharmaceutically acceptable salt, and one or more pharmaceutically acceptable carrier.

[0104] In one aspect, the present application relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of the application, or a pharmaceutically acceptable salt, and one or more phar ceutically acceptable carrier.

[0105] In one aspect, the present application relates to a pharmaceutical composition comprising a compound of the application, and one or more pharmaceutically acceptable carrier.

[0106] In one aspect, the present application relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of the application, and one or more pharmaceutically acceptable carrier.

[0107] The present disclosure further provides a use of a compound of Formula I, II, or III, or a stereoisomer, or a pharmaceutically acceptable salt thereof in a method of treating cancer in a patient in need thereof.

[0108] The present disclosure further provides a compound of Formula I, II, or III, or a stereoisomer, or a pharmaceutically acceptable salt thereof for use in a method of treating cancer in a patient in need thereof.

[0109] The present disclosure further provides a compound of Formula I, II, or III, or a stereoisomer, or a pharmaceutically acceptable salt thereof for use in the manufacture of a medicament for the treatment of cancer in a patient in need thereof.

[0110] The present disclosure further provides a method of inhibiting the interaction between menin and MLL comprising contacting the menin and MLL with a compound of Formula I, II, or III, or a stereoisomer, or a pharmaceutically acceptable salt thereof.

[0111] The present disclosure further provides a method of inhibiting the interaction between menin and MLL comprising contacting the menin and MLL with an effective amount of a43707-02999 / WO (SYND-070 / 001WO)

[0112] compound of Formula I, II, or III, or a stereoisomer, or a pharmaceutically acceptable salt thereof.

[0113] The present disclosure further provides a method of inhibiting the interaction between menin and MLL comprising contacting the menin and Mid., with a pharmaceutical composition comprising a compound of Formula I, II, or III, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

[0114] The present disclosure further provides a method of treating cancer in a patient comprising administering to the patient a therapeutically effective amount of a compound of Formula I, II, or III, a stereoisomer, or a pharmaceutically acceptable salt thereof.

[0115] The present disclosure further provides a method of inhibiting the interaction between menin and Mid., comprising contacting the menin and MLL with a compound of Formula I, II, or III, a stereoisomer, or a pharmaceutically acceptable salt thereof.

[0116] The present disclosure further provides a method of treating cancer in a patient comprising administering to the patient an effective amount of a compound of Formula I, II, or III, a stereoisomer, or a pharmaceutically acceptable salt thereof.

[0117] The present disclosure further provides a method of treating cancer in a patient comprising administering to the patient a compound of Formula I, II, or III, a stereoisomer, or a pharmaceutically acceptable salt thereof.

[0118] The present disclosure further provides a method of treating cancer in a patient comprising administering to the patient a pharmaceutical composition comprising a compound of Formula I, II, or III, a stereoisomer, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

[0119] The present disclosure further provides a pharmaceutical composition comprising a compound of Formula I, II, or III, a stereoisomer, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

[0120] The present disclosure further provides a pharmaceutical composition comprising a salt or crystalline form of a compound of Formula I, II, or III, and at least one pharmaceutically acceptable carrier.

[0121] The present disclosure further provides a compound of Formula I, II, or III, wherein the compound is useful for the treatment of cancer and wherein the compound minimizes hERG binding.

[0122] In some embodiments, present disclosure further provides a method of preparing a compound herein according to a scheme of the present disclosure or synthetic description in the Examples.43707-02999 / WO (SYND-070 / 001WO)

[0123] In some embodiments, present disclosure further provides an intermediate useful in the preparation of any one of the compounds herein.

[0124] The details of the disclosure are set forth in the accompanying description below. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application, illustrative methods and materials are now described. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be limiting. Other features, objects, and advantages of the disclosure will be apparent from the description and from the claims. In the specification and the appended claims, the singular forms also include the plural unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0125] DETAILED DESCRIPTION

[0126] In some embodiments, the present disclosure is directed to a compound of Formula I,

[0127]

[0128] a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0129] V is N or CH;

[0130] Y is N or CH;43707-02999 / WO (SYND-070 / 001WO)

[0131] e

[0132]

[0133]

[0134] Cy is, wherein e and f indicate points of attachment to the remainder of the molecule;

[0135] is

[0136] (a) C 1-6 haloalky I, Ci-6 alkoxy, C?-6 alkenyl, C2-6 alkynyl, CRioaryl, 5- to 10- membered heteroaryl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-]2cycloalkyl-Ci-6alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, or -(4- to 10-membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-ioaryl, 5- to 10-membered heteroaryl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, -Co-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, and -(4- to 10-membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0137] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0138] each Rlsis independently oxo or =NR4a;

[0139] (c) -C1-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rias'

[0140] each Riasis independently halo, oxo, Cj-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0141] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0142] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=::O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or43707-02999 / WO (SYND-070 / 001WO)

[0143] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0144] each Rlcsis independently halo, oxo, Cj-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the Ci-6 alkyl or Ci-6 haloalkyl is optionally substituted with one or more Ci-6 alkoxy;

[0145] each R3a’ is independently H, C1-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[0146] each R3b’ is independently H, Ct-6 alkyl, Cj-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0147] each3C’ is independently H, Cj-6 alkyl, Ci-6 haloalkyl, €3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0148] R2is H, C1-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, -Ce-io aryl-C1-6 alkyl, -C3-12 cycloalkyl-C 1-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, or -(3- to 12-membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, Ci-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -Cj-n cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, and -(3- to 12-membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from R8; or

[0149] R1and R2form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0150] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, Ci-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, Ci-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, Ci-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, Ci-6 alkyl sulfonyl, carboxy, aminocarbonyl, Cj -6 alkylcarbonyl, and C1-6 alkoxy carbonyl;

[0151] Ring A is 6- to 10-membered aryl or 5- to 10-membered heteroaryl, wherein the 6- to 10-membered aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Cj-6 alkoxy;43707-02999 / WO (SYND-070 / 001WO)

[0152] X3is H or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S( O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0153] when m is 0:

[0154] R3is Ci-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, wherein the Cj-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with one or more R3as;

[0155] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, or N(R4a)(R4b);

[0156] when m is 1:

[0157] R3is H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-10 aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3- 12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a, or

[0158] R3forms a 3- to 12-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[0159] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[0160] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-10aryl, or N(R4a’)(R4b’);

[0161] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);

[0162] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0163] each RNIS independently H, Ci-6 alkyl, or Ci-6 haloalkyl;43707-02999 / WO (SYND-070 / 001WO)

[0164] ni is 0 or 1; and

[0165] n is 1, 2, or 3;

[0166] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0167] In some embodiments, the present disclosure is directed to a compound of Formula II:

[0168] ZR3

[0169] N J

[0170] R2I I

[0171] I I IlY

[0172]

[0173] Vx.

[0174] F N Formula II, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0175] V is N or CH;

[0176] Y is N or CH;

[0177] R1is

[0178] (a) C i-6 haloalky 1, Ci-e alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, 5- to 10- membered heteroaryl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, -Ce-io aryl-Cj-6 alkyl, -C3-12 cycloalkyl-Cj-6 alkyl, -(5- to I O-membered heteroaryl)-Ci-6 alkyl, or -(4- to 10-membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10aryl, 5- to 10-membered heteroaryl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, and -(4- to 10-membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0179] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0180] each R,sis independently oxo or =NR4a;

[0181] (c) -Cj-6 alkylene-N(R3a’)(R3b’) or -Cs-n cycloalkylene-N(

[0182]

[0183] R3iV)(R3b’), wherein the Cj-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rias;43707-02999 / WO (SYND-070 / 001WO)

[0184] each Rlasis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N

[0185]

[0186] (R3a’)(R3b’), or S(===O)2R3a’;

[0187] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0188] each Rlbsis independently halo, oxo, OR3a’, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[0189] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more R,cs;

[0190] each Rlcsis independently halo, oxo, Cj-6 alkyl, C1-6 haloalkyl, C(:::O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the Ci-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0191] each R3a’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C(O)R3c’, €3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Cj-6 alkoxy;

[0192] each R3b’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0193] each R3C’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl;

[0194] R2is H, Cj-6 alkyl, Cue haloalkyl, Cj-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Cg-io and, C 3-12 cycloalkyl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, -Cg-ioaryl-C1-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, or -(3- to 12-membered heterocycloalkyl)-Ci-6 alkyl, wherein said Ci-6 alkyl, C 1-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, -Cg-io aryl-Ci-6 alkyl, -63-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, and -(3- to 12-membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from R8; or

[0195] R1and R2form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;43707-02999 / WO (SYND-070 / 001WO)

[0196] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, Ci-6 alkyl, C6-10 aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, Ci-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyd, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C1-6 alkylthio, C1-6 alkyl sulfinyl, Cj-6 alkyl sulfonyl, carboxy, aminocarbonyl, Ci -6 alkylcarbonyl, and C1-6 alkoxy carbonyl;

[0197] R3is C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, wherein the C1-6 alkyl, C2-6 alkenyl, or C2- 6 alkynyl is optionally substituted with one or more R3as;

[0198] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b\ or N(R4a)(R4b);

[0199] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0200] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’);

[0201] each R4a’ andR4b’ is independently H, Ci-6 alkyl, C 3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0202] each RNIS independently H, Ci-6 alkyl, or Cj-6 haloalkyl;

[0203] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0204] In some embodiments, the present disclosure is directed to a compound of Formula III.

[0205] R3

[0206]

[0207] a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0208] R1is C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom43707-02999 / WO (SYND-070 / 001WO)

[0209] ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0210] each Rlesis independently halo, oxo, Ci-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a\ or S(::::O)2R3a’, wherein the C1-6 alkyl or Ci-6 haloalkyl is optionally substituted with one or more Cj-6 alkoxy;

[0211] each Rja’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3e’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[0212] each R3b’ is independently H, Cj-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0213] each R3C’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0214] R2is H, Cj-6 alkyl, C 1-6 haloalkyl, Cj-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, -Ce-ioaryl-C1-6 alkyl, -C3-i2cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, or -(3- to 12-membered heterocycloalkyl)-Ci-6 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, -C6-10 aryl-Cj-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, and -(3- to 12-membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rs;

[0215] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-6 cycloalkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, Ci-6 alkylamino, di(Ci-6 alkyl'Jamino, thiol, C 1-6 alkylthio, Cj-6 alkylsulfinyl, Ci-6 alkylsulfonyl, carboxy, aminocarbonyl, C 1-6 alkylcarbonyl, and Ci-6 alkoxy carbonyl;

[0216] R3is Cj-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, wherein the Ci-6 alkyl, C2-6 alkenyl, or C2- 6 alkynyl is optionally substituted with one or more R3as;

[0217] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, or N(R4a)(R4b);

[0218] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[0219] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl,43707-02999 / WO (SYND-070 / 001WO)

[0220] or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b;);

[0221] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0222] each Rxis independently H, C1-6 alkyl, or Cj-6 haloalkyl.

[0223] Embodiments

[0224] For any of Formulae I, II, and III where applicable, the following embodiments are considered both alone and in conjunction with another where a stable compound is formed.

[0225] In some embodiments, the compound is of Formula III, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0226] R1is C3-12 cycloalkyl substituted with one 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more C1-6 alkyl or C1-6 haloalkyl;

[0227] R2is H, C1-6 alkyl, or C 1-6 haloalkyl;

[0228] R3is Ci-6 alkyl optionally substituted with one or more halo, OH, O(Ci-6 alkyl), or OBn. In some embodiments, the compound is of Formula III, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0229] R1is C3-12 cycloalkyl substituted with one pyrrolidinyl; and wherein the C3-12 cycloalkyl is optionally substituted with one or more C1-6 alkyl or Cj-6 haloalkyl;

[0230] R2is H, C1-6 alkyl, or C 1-6 haloalkyl;

[0231] R3is C1-6 alkyl optionally substituted with one or more halo, OH, O(Ci-6 alkyl), or OBn.

[0232] Embodiments covering C

[0233] In some embodiments, V is N or CH.

[0234] In some embodiments, V is N.

[0235] In some embodiments, V is CH.

[0236] Embodiments covering Y

[0237] In some embodiments, Y is N or CH.

[0238] In some embodiments, Y is N.

[0239] In some embodiments, Y is CH.

[0240] Embodiments covering Cy43707-02999 / WO (SYND-070 / 001WO)

[0241] e

[0242] £

[0243] In some embodiments, C

[0244]

[0245] y is, wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:

[0246] Ring A is 6- to 10-membered aryl or 5- to 10-membered heteroaryl, wherein the 6- to 10-membered aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Cj-6 alkoxy;

[0247] X3is H or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0248] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0249] each R4bis independently H

[0250]

[0251] , S(==O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b?);

[0252] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0253] n is 1, 2, or 3.

[0254] e

[0255]

[0256] In some embodiments, Cy is

[0257]

[0258] , wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:

[0259] Ring A is 6- to 10-membered aryl optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;

[0260] X3is H or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0261] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);43707-02999 / WO (SYND-070 / 001WO)

[0262] each R4bis independently H, S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, Ca-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);

[0263] each R4a’ and R4b?is independently H, Ci-6 alkyl, Cs-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0264] n is 1, 2, or 3.

[0265] e

[0266] y3 7-7

[0267] £

[0268] In some embodiments, C

[0269]

[0270] y is, wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:

[0271] Ring A is 6- to 9-membered aryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ct-6 alkoxy;

[0272] X3is H or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0273] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io and, or N(R4a’)(R4b’);

[0274] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, Ca-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);

[0275] each R4a’ and R4b’ is independently H, Ci-6 alkyl, Cs-n cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0276] n is 1, 2, or 3.

[0277] e

[0278] y3 " Tk

[0279] X> C'N /

[0280] £

[0281] In some embodiments, C

[0282]

[0283] y is, wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:43707-02999 / WO (SYND-070 / 001WO)

[0284] Ring A is 6- to 8-membered aryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;

[0285] X3is H or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0286] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);

[0287] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b;);

[0288] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0289] n is 1, 2, or 3.

[0290] e

[0291] £

[0292] In some embodiments, C

[0293]

[0294] y is, wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:

[0295] Ring A is 6- to 7-membered aryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;

[0296] X3is H or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0297] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0298] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b?);

[0299] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0300] n is 1, 2, or 3.43707-02999 / WO (SYND-070 / 001WO)

[0301] e

[0302] £

[0303] In some embodiments, C

[0304]

[0305] y is, wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:

[0306] Ring A is 6-membered aryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;

[0307] X3is H or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0308] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0309] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’);

[0310] each R4a’ andR4b’ is independently H, C'i- alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0311] n is 1, 2, or 3.

[0312] e

[0313]

[0314] In some embodiments, Cy is

[0315]

[0316] , wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:

[0317] Ring A is 7-membered aryl optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0318] X3is H or C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0319] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);43707-02999 / WO (SYND-070 / 001WO)

[0320] each R4bis independently H, S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, Ca-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);

[0321] each R4a’ and R4b?is independently H, Ci-6 alkyl, Cs-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0322] n is 1, 2, or 3.

[0323] e

[0324] y3 7-7

[0325] £

[0326] In some embodiments, C

[0327]

[0328] y is, wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:

[0329] Ring A is 8-membered aryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci -6 alkoxy;

[0330] X3is H or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0331] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C

[0332]

[0333] e-io and, or N(R4a’)(R4b’);

[0334] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, Ca-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);

[0335] each R4a’ and R4b’ is independently H, Ci-6 alkyl, Cs-n cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0336] n is 1, 2, or 3.

[0337] e

[0338] y3 Tk

[0339] X> C'N /

[0340] £

[0341] In some embodiments, C

[0342]

[0343] y is, wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:43707-02999 / WO (SYND-070 / 001WO)

[0344] Ring A is 9-membered aryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;

[0345] X3is H or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0346] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);

[0347] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b;);

[0348] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0349] n is 1, 2, or 3.

[0350] e

[0351] £

[0352] In some embodiments, C

[0353]

[0354] y is, wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:

[0355] Ring A is 10-membered aryl optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0356] X3is H or C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0357] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0358] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b?);

[0359] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0360] n is 1, 2, or 3.43707-02999 / WO (SYND-070 / 001WO)

[0361] e

[0362] £

[0363] In some embodiments, C

[0364]

[0365] y is, wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:

[0366] Ring A is 5- to 10-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;

[0367] X3is H or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0368] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0369] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’);

[0370] each R4a’ andR4b’ is independently H, C'i- alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0371] n is 1, 2, or 3.

[0372] e

[0373]

[0374] In some embodiments, Cy is

[0375]

[0376] , wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:

[0377] Ring A is 5- to 9-membered heteroaryl optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0378] X3is H or C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0379] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);43707-02999 / WO (SYND-070 / 001WO)

[0380] each R4bis independently H, S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, Ca-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);

[0381] each R4a’ and R4b?is independently H, Ci-6 alkyl, Cs-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0382] n is 1, 2, or 3.

[0383] e

[0384] y3 7-7

[0385] £

[0386] In some embodiments, C

[0387]

[0388] y is, wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:

[0389] Ring A is 5- to 8-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;

[0390] X3is H or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0391] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io and, or N(R4a’)(R4b’);

[0392] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, Ca-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);

[0393] each R4a’ and R4b’ is independently H, Ci-6 alkyl, Cs-n cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0394] n is 1, 2, or 3.

[0395] e

[0396] y3 " Tk

[0397] X> C'N /

[0398] £

[0399] In some embodiments, C

[0400]

[0401] y is, wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:43707-02999 / WO (SYND-070 / 001WO)

[0402] Ring A is 5- to 7-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;

[0403] X3is H or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0404] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);

[0405] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b;);

[0406] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0407] n is 1, 2, or 3.

[0408] e

[0409] £

[0410] In some embodiments, C

[0411]

[0412] y is, wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:

[0413] Ring A is 5- to 6-membered heteroaryl optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0414] X3is H or C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0415] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0416] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b?);

[0417] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0418] n is 1, 2, or 3.43707-02999 / WO (SYND-070 / 001WO)

[0419] e

[0420] £

[0421] In some embodiments, C

[0422]

[0423] y is, wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:

[0424] Ring A is 5-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;

[0425] X3is H or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0426] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0427] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’);

[0428] each R4a’ andR4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0429] n is 1, 2, or 3.

[0430] e

[0431]

[0432] In some embodiments, Cy is

[0433]

[0434] , wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:

[0435] Ring A is 6-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0436] X3is H or C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0437] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);43707-02999 / WO (SYND-070 / 001WO)

[0438] each R4bis independently H, S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, Ca-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);

[0439] each R4a’ and R4b?is independently H, Ci-6 alkyl, Cs-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0440] n is 1, 2, or 3.

[0441] e

[0442] y3 7-7

[0443] £

[0444] In some embodiments, C

[0445]

[0446] y is, wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:

[0447] Ring A is 7-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ct-6 alkoxy;

[0448] X3is H or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0449] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io and, or N(R4a’)(R4b’);

[0450] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, Ca-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);

[0451] each R4a’ and R4b’ is independently H, Ci-6 alkyl, Cs-n cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0452] n is 1, 2, or 3.

[0453] e

[0454] y3 " Tk

[0455] X> C'N /

[0456] £

[0457] In some embodiments, C

[0458]

[0459] y is, wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:43707-02999 / WO (SYND-070 / 001WO)

[0460] Ring A is 8-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;

[0461] X3is H or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0462] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);

[0463] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b;);

[0464] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0465] n is 1, 2, or 3.

[0466] e

[0467] £

[0468] In some embodiments, C

[0469]

[0470] y is, wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:

[0471] Ring A is 9-membered heteroaryl optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;

[0472] X3is H or C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0473] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0474] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b?);

[0475] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0476] n is 1, 2, or 3.43707-02999 / WO (SYND-070 / 001WO)

[0477] e

[0478]

[0479] In some embodiments, Cy is

[0480]

[0481] wherein e and f indicate points of attachment to the remainder of the molecule, and wherein:

[0482] Ring A is 10-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;

[0483] X3is H or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0484] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0485] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’);

[0486] each R4a’ andR4b’ is independently H, C'i- alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0487] n is 1, 2, or 3.

[0488]

[0489]

[0490] , wherein e and f indicate points of attachment to the remainder of the molecule.43707-02999 / WO (SYND-070 / 001WO)

[0491]

[0492] e and f indicate points of attachment to the remainder of the molecule.

[0493] In some embodiments,

[0494]

[0495] wherein e and f indicate points of attachment to the remainder of the molecule.

[0496] Embodiments covering Ring A

[0497] In some embodiments, Ring A is 6- to 10-membered aryl or 5- to 10-membered heteroaryl, wherein the 6- to 10-membered aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more C1-6alkyl, halo, OH, CN, or C1-6alkoxy.

[0498] In some embodiments, Ring A is 6- to 10-membered aryl optionally substituted with one or more C1-6alkyl, halo, OH, CN, or Ci-6 alkoxy.

[0499] In some embodiments, Ring A is 6- to 9-membered aryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[0500] In some embodiments, Ring A is 6- to 8-membered and optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[0501] In some embodiments, Ring A is 6- to 7-membered aryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[0502] In some embodiments. Ring A is 6-membered aryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[0503] In some embodiments, Ring A is 7-membered aryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[0504] In some embodiments. Ring A is 8-membered aryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[0505] In some embodiments, Ring A is 9-membered aryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[0506] In some embodiments, Ring A is 10-membered aryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.43707-02999 / WO (SYND-070 / 001WO)

[0507] In some embodiments, Ring A is 6-membered aryl.

[0508] In some embodiments, Ring A is 7-membered aryl.

[0509] In some embodiments, Ring A is 8-membered aryl.

[0510] In some embodiments, Ring A is 9-membered aryl.

[0511] In some embodiments, Ring A is 10-membered aryl.

[0512] In some embodiments, Ring A is a phenyl ring.

[0513] In some embodiments, Ring A is a pyridine ring.

[0514] In some embodiments, Ring A is 5- to 10-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Cj-6 alkoxy.

[0515] In some embodiments, Ring A is 5- to 9-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[0516] In some embodiments, Ring A is 5- to 8-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Cj-6 alkoxy.

[0517] In some embodiments, Ring A is 5- to 7-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[0518] In some embodiments, Ring A is 5- to 6-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[0519] In some embodiments, Ring A is 5-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[0520] In some embodiments. Ring A is 6-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[0521] In some embodiments, Ring A is 7-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[0522] In some embodiments, Ring A is 8-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[0523] In some embodiments, Ring A is 9-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[0524] In some embodiments, Ring A is 10-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[0525] In some embodiments, Ring A is 5- to 10-membered heteroaryl.

[0526] In some embodiments, Ring A is 5- to 9-membered heteroaryl.

[0527] In some embodiments, Ring A is 5- to 8-membered heteroaryl.

[0528] In some embodiments, Ring A is 5- to 7-membered heteroaryl.

[0529] In some embodiments, Ring A is 5- to 6-membered heteroaryl.43707-02999 / WO (SYND-070 / 001WO)

[0530] In some embodiments, Ring A is 5-membered heteroaryl.

[0531] In some embodiments, Ring A is 6-membered heteroaryl.

[0532] In some embodiments, Ring A is 7-membered heteroaryl.

[0533] In some embodiments, Ring A is 8-membered heteroaryl.

[0534] In some embodiments, Ring A is 9-membered heteroaryl.

[0535] In some embodiments, Ring A is 10-membered heteroaryl.

[0536] Embodiments covering X3

[0537] In some embodiments, X3is H or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0538] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0539] each R4bis independently H

[0540]

[0541] , S(==O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’ ); and

[0542] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0543] In some embodiments, X3is H.

[0544] In some embodiments, X3is C1-6 alkyl optionally substituted with one or more halo, 3-to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0545] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0546] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0547] each R4a’ and R4b’ is independently II, C1-6 alkyl, C3-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0548] In some embodiments, X3is C1-5 alkyl optionally substituted with one or more halo, 3-to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);43707-02999 / WO (SYND-070 / 001WO)

[0549] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0550] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0551] each R4a’ andR4b’ is independently H, C'i- alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0552] In some embodiments, X3is C1-4 alkyl optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0553] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[0554] each R4bis independently H, S(=O)2R4b’, C(O)OR4b', C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0555] each R4a’ and R4b’ is independently H, C1-6 alkyl, Cs-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0556] In some embodiments, X3is C1-3 alkyl optionally substituted with one or more halo, 3-to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0557] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0558] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0559] each R4a’ and R4b’ is independently II, C1-6 alkyl, Cs-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0560] In some embodiments, X3is Ci-2alkyl optionally substituted with one or more halo, 3-to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);43707-02999 / WO (SYND-070 / 001WO)

[0561] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0562] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0563] each R4a’ andR4b’ is independently H, C'i- alkyl, C 3.12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0564] In some embodiments, X3is methyl optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), orN(R4a)(R4b);

[0565] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[0566] each R4bis independently I

[0567]

[0568] I, S(==O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6alkyl is optionally substituted with C1-6alkoxy or C(O)N(R4a’)(R4b’); and

[0569] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0570] In some embodiments, X3is ethyl optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(::::O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), orN(R4a)(R4b);

[0571] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0572] each R4bis independently H

[0573]

[0574] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0575] each R4a’ and R4b’ is independently H, C1-6 alkyl, Cs-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0576] In some embodiments, X3is propyl optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), orN(R4a)(R4b);

[0577] each R4ais independently H, CN, or C1-6alkyl optionally substituted with one or more halo, C6-10aryl, or N(R4a’)(R4b’);

[0578] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl,43707-02999 / WO (SYND-070 / 001WO)

[0579] or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b;); and

[0580] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0581] In some embodiments, X is butyl optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), orN(R4a)(R4b);

[0582] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0583] each R4bis independently H

[0584]

[0585] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b?); and

[0586] each R4a’ and R4b’ is independently II, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0587] In some embodiments, X3is pentyl optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0588] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-10aryl, or N(R4a’)(R4b’);

[0589] each R4bis independently H, S(=O)2R4b’, C(O)OR4b', C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0590] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0591] In some embodiments, X3is hexyl optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);

[0592] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[0593] each R4bis independently H, S(===O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0594] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.43707-02999 / WO (SYND-070 / 001WO)

[0595] In some embodiments, X3is C1-6alkyl.

[0596] In some embodiments, X3is C1-5alkyl.

[0597] In some embodiments, X3is C1-4alkyl.

[0598] In some embodiments, X3is C1-3alkyl.

[0599] In some embodiments, X3is C1-2alkyl.

[0600] In some embodiments, X3is methyl.

[0601] In some embodiments, X3is ethyl.

[0602] In some embodiments, X3is propyl.

[0603] In some embodiments, X3is isopropyl.

[0604] In some embodiments, X3is butyl.

[0605] In some embodiments, X3is tert-butyl.

[0606] In some embodiments, X3is pentyl.

[0607] In some embodiments, X3is hexyl.

[0608] In some embodiments, X3is Ci-6 alkyl substituted with one or more -OH.

[0609] In some embodiments, X3is C1-5 alkyl substituted with one or more -OH.

[0610] In some embodiments, X3is C1-4 alkyl substituted with one or more -OH.

[0611] In some embodiments, X3is C1-3 alkyl substituted with one or more -OH.

[0612] In some embodiments, X3is Cj-2 alkyl substituted with one or more -OH.

[0613] In some embodiments, X

[0614]

[0615] 3is -CH2(OH), -CH2-CH2(OH), or -CH2-CH2-CH2(OH). In some embodiments, X3is C1-6 alkyl substituted with one or more oxo.

[0616] In some embodiments, X3is C1-5 alkyl substituted with one or more oxo.

[0617] In some embodiments, X3is Cj-4 alkyl substituted with one or more oxo.

[0618] In some embodiments, X3is Cj-3 alkyl substituted with one or more oxo.

[0619] In some embodiments, X3is C1-2 alkyl substituted with one or more oxo.

[0620] In some embodiments, X3is C1-6 alkyl substituted with one or more CN.

[0621] In some embodiments, X3is C1-5 alkyl substituted with one or more CN.

[0622] In some embodiments, X3is Cj-4 alkyl substituted with one or more CN.

[0623] In some embodiments, X3is C1-3 alkyl substituted with one or more CN.

[0624] In some embodiments, X3is C1-2 alkyl substituted with one or more CN.

[0625] In some embodiments, X3is C1-6 alkyl substituted with one or more C(=O)N(R4a)(R4b); each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[0626] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl,43707-02999 / WO (SYND-070 / 001WO)

[0627] or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0628] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0629] In some embodiments, X3is C1-5 alkyl substituted with one or more C(=O)N(R4a)(R4b); each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);

[0630] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0631] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0632] In some embodiments, X3is C1-4alkyl substituted with one or more C(=O)N(R4a)(R4b); each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);

[0633] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0634] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0635] In some embodiments, X3is Ci-3 alkyl substituted with one or more C(=O)N(R4a)(R4b); each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);

[0636] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0637] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0638] In some embodiments, X3is C1-2alkyl substituted with one or more C(=O)N(R4a)(R4b); each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);43707-02999 / WO (SYND-070 / 001WO)

[0639] each R4bis independently H, S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, Ca-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0640] each R4a’ and R4b?is independently H, Ci-6 alkyl, Cs-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0641] In some embodiments, X3is methyl substituted with one or more C(=O)N(R4a)(R4b); each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io and, or N(R4a’)(R4b’);

[0642] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, Ca-i2cycloalkyl, Cg-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0643] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0644] In some embodiments, X3is ethyl substituted with one or more C(=O)N(R4a)(R4b); each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io and, or N(R4a’)(R4b’);

[0645] each R4bis independently H, S(=O)2R4b’, C(O)OR4b', C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, Ca-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0646] each R4a’ and R4b?is independently H, C1-6 alkyl, Cs-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0647] In some embodiments, X3is propyl substituted with one or more C(=O)N(R4a)(R4b); each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io and, or N(R4a’)(R4b’);

[0648] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, Ca-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0649] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0650] In some embodiments, X3is butyl substituted with one or more C(=O)N(R4a)(R4b);43707-02999 / WO (SYND-070 / 001WO)

[0651] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0652] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0653] each R4a’ andR4b’ is independently H, C'i- alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0654] In some embodiments, X3is pentyl substituted with one or more C(=O)N(R4a)(R4b); each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0655] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0656] each R4a’ andR4b’ is independently H, C'i- alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0657] In some embodiments, X3is hexyl substituted with one or more C(=O)N(R4a)(R4b); each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0658] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0659] each R4a’ andR4b’ is independently H, C'i- alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0660] In some embodiments, X3is Cj-6 alkyl substituted with one or more N(R4a)(R4b); each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0661] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and43707-02999 / WO (SYND-070 / 001WO)

[0662] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0663] In some embodiments, X3is C1-5 alkyl substituted with one or more N(R4a)(R4b); each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io and, or N(R4a’)(R4b’);

[0664] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with Cj-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0665] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0666] In some embodiments, X3is C1-4 alkyl substituted with one or more N(R4a)(R4b); each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[0667] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Cj-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0668] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0669] In some embodiments, X3is C1-3 alkyl substituted with one or more N(R4a)(R4b); each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io and, or N(R4a’)(R4b’);

[0670] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Cj-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0671] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0672] In some embodiments, X3is C1-2 alkyl substituted with one or more N(R4a)(R4b); each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[0673] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl,43707-02999 / WO (SYND-070 / 001WO)

[0674] or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0675] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0676] In some embodiments, X3is methyl substituted with one or more N(R4a)(R4b); each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);

[0677] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0678] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0679] In some embodiments, X3is ethyl substituted with one or more N(R4a)(R4b);

[0680] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);

[0681] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0682] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0683] In some embodiments, X3is propyl substituted with one or more N(R4a)(R4b); each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);

[0684] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0685] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0686] In some embodiments, X3is butyl substituted with one or more N(R4a)(R4b); each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);43707-02999 / WO (SYND-070 / 001WO)

[0687] each R4bis independently H, S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, Ca-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0688] each R4a’ and R4b?is independently H, Ci-6 alkyl, Ca-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0689] In some embodiments, X3is pentyl substituted with one or more N(R4a)(R4b); each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io and, or N(R4a’)(R4b’);

[0690] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, Ca-i2cycloalkyl, Cg-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0691] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0692] In some embodiments, X3is hexyl substituted with one or more N(R4a)(R4b); each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io and, or N(R4a’)(R4b’);

[0693] each R4bis independently H, S(=O)2R4b’, C(O)OR4b', C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, Ca-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[0694] each R4a’ and R4b?is independently H, C1-6 alkyl, Ca-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0695] Embodiments covering R1

[0696] In some embodiments, R1is

[0697] (a) Cj-6 haloalkyl, Cj-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, 5- to 10- membered heteroaryd, Cs-i2cycloalkyl, 3- to 12-membered heterocycloalkyl, -Ce-io aryl-Cj-6 alkyl, -Ca-n cycloalkyl-Cj-6 alkyl, -(5- to I O-membered heteroaryl)-Ci-6 alkyl, or -(4- to 10-membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 haloalkyl, Ci-e alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, 5- to 10-membered heteroaryl, Ca-i2cycloalkyl, 3- to 12-membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5- to 1 O-membered heteroaryl)-Ci-6 alkyl, and -(4-43707-02999 / WO (SYND-070 / 001WO)

[0698] to 10-membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0699] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0700] each Rlsis independently oxo or =NR4a;

[0701] (c) -Ci-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more R!as;

[0702] each Riasis independently halo, oxo, Ci-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N

[0703]

[0704] (R3a’)(R3b’), or S(===O)2R3a’;

[0705] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0706] each Rlbsis independently halo, oxo, OR3a’, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[0707] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more R,cs;

[0708] each Rlcsis independently halo, oxo, Cj-6 alkyl, C1-6 haloalkyl, C(:::O)(R3a’),

[0709]

[0710] N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the Ci-6 alkyl or Cj-6 haloalkyl is optionally substituted with one or more Ci-6 alkoxy;

[0711] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, €3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyd are optionally substituted with Cj-6 alkoxy;

[0712] each R3b’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl;

[0713] each R3C’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl;

[0714] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-6 cycloalkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, cyano-Ci.3 alkyl, HO-C1-3 alkyl,43707-02999 / WO (SYND-070 / 001WO)

[0715] amino, Ci-6 alkylamino, di(Ci-6 alkyl)amino, thiol, Ci-6 alkylthio, Ci-6 alkylsulfinyl, Ci-6 alkyl sulfonyl, carboxy, aminocarbonyl, Ci-6 alkylcarbonyl, and Ci-6 alkoxycarbonyl;

[0716] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[0717] each R4a’ and R4b?is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0718] each RNIS independently H, Ci-6 alkyl, or Ci-6 haloalkyl.

[0719] In some embodiments, R1is C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce- 10 aryl, 5- to 10-membered heteroaryl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, - Ce-ioaryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-C 1-6 alkyl, or -(4- to I O-membered heterocycloalkyl)-Ci-6 alkyl, wherein said Ct-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, 5- to 10-membered heteroaryl, C3-12 cycloalkyl, 3- to 12- membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, and -(4- to 10-membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rs;

[0720] each Rgis independently selected from OH, NO?, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, C6-10aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-6 cycloalkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, cyano-Ci.3 alkyl, HO-C1-3 alkyl, amino, Ci-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, Ci-6 alkylsulfinyl, Cis alkyl sulfonyl, carboxy, aminocarbonyl, C 1-6 alkylcarbonyl, and Cis alkoxycarbonyl;

[0721] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0722] each Rjjis independently H, Ci-6 alkyl, or Cj-6 haloalkyl.

[0723] In some embodiments, R1is 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0724] each Rlsis independently oxo or =NR4a;

[0725] each R4ais independently H, CN, or C1-6alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’); and

[0726] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0727] In some embodiments, R1is 3- to 11-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 11-membered heterocycloalkyl is optionally substituted with one or two Rls;43707-02999 / WO (SYND-070 / 001WO)

[0728] each Rlsis independently oxo or =NR4a;

[0729] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’); and

[0730] each R4a’ and R411’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0731] In some embodiments, R1is 3- to 10-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 10-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0732] each Rlsis independently oxo or =NR4a;

[0733] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’); and

[0734] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0735] In some embodiments, R1is 3- to 9-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 9-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0736] each Rlsis independently oxo or =NR4a;

[0737] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’); and

[0738] each R4a’ and R4b’ is independently II, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0739] In some embodiments, R1is 3- to 8-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 8-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0740] each Risis independently oxo or =NR4a;

[0741] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’); and

[0742] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0743] In some embodiments, R1is 3- to 7-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 7-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0744] each Risis independently oxo or =NR4a;43707-02999 / WO (SYND-070 / 001WO)

[0745] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’); and

[0746] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0747] In some embodiments, R1is 3- to 6-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 6-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0748] each Rlsis independently oxo or =NR4a;

[0749] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’); and

[0750] each R4a’ and R4b’ is independently II, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0751] In some embodiments, R1is 3- to 5-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 5-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0752] each Risis independently oxo or =NR4a;

[0753] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C

[0754]

[0755] e-io and, or N(R4a’)(R4b’); and

[0756] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0757] In some embodiments, R1is 3- to 4-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 4-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0758] each Risis independently oxo or =NR4a;

[0759] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’); and

[0760] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0761] In some embodiments, R1is 3-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3-membered heterocycloalkyl is optionally substituted with one or two Ris;

[0762] each Rlsis independently oxo or =NR4a;

[0763] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’); and43707-02999 / WO (SYND-070 / 001WO)

[0764] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0765] In some embodiments, R1is 4-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 4-membered heterocycloalkyl is optionally substituted with one or two R!s;

[0766] each Risis independently oxo or =NR4a;

[0767] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’); and

[0768] each R4a’ and R4b?is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0769] In some embodiments, R1is 5-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 5-membered heterocycloalkyl is optionally substituted with one or two Ris;

[0770] each Rlsis independently oxo or =NR4a;

[0771] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’); and

[0772] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0773] In some embodiments, R1is 6-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 6-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0774] each Rlsis independently oxo or::::NR4a;

[0775] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’); and

[0776] each R4a’ andR4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0777] In some embodiments, R1is 7-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 7-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0778] each Rlsis independently oxo or =NR4a;

[0779] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’); and

[0780] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.43707-02999 / WO (SYND-070 / 001WO)

[0781] In some embodiments, R1is 8-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 8-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0782] each Rlsis independently oxo or::::NR4a;

[0783] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’); and

[0784] each R4a’ andR4b’ is independently H, C'i- alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0785] In some embodiments, R1is 9-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 9-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0786] each Rlsis independently oxo or =NR4a;

[0787] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’); and

[0788] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0789] In some embodiments, R1is 10-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 10-membered heterocycloalkyl is optionally substituted with one or two Ris;

[0790] each Risis independently oxo or:::NR4a;

[0791] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’); and

[0792] each R4a’ and R4b?is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0793] In some embodiments, R1is 11-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 11 -membered heterocycloalkyl is optionally substituted with one or two Ris;

[0794] each Risis independently oxo or =NR4a;

[0795] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’); and

[0796] each R4a’ and R411’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.43707-02999 / WO (SYND-070 / 001WO)

[0797] In some embodiments, R1is 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0798] each Rlsis independently oxo or::::NR4a;

[0799] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’); and

[0800] each R4a’ andR4b’ is independently H, Ci-6 alkyl, C 3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0801] In some embodiments, R1is -Ci-6 alkylene-N(R3a,)(R3b’) or -C 3-12 cycloalkylene- N(R3a’)(Rjb’), wherein the Ci-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;

[0802] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(==O)2R3a’;

[0803] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[0804] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0805] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0806] In some embodiments, Rlis -C1-6 alkylene-N(R3a’)(R3b’) optionally substituted with one or more Rias;

[0807] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0808] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Cj-6 alkoxy;

[0809] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0810] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[0811] In some embodiments, R1is -C1-5 alkylene-N(Rja’)(R3b’) optionally substituted with one or more Rias;43707-02999 / WO (SYND-070 / 001WO)

[0812] each Rlasis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3i)(R3b’), or S(===O)2R3a’;

[0813] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Cj-6 alkoxy;

[0814] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0815] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0816] In some embodiments, R1is -C1-4 alkylene-N(Rja’)(R3b’) optionally substituted with one or more Rias;

[0817] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(:=:O)2R3a’;

[0818] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[0819] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0820] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0821] In some embodiments, Rlis -C1-3 alkylene-N(R3a’)(R3b’) optionally substituted with one or more Rias;

[0822] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0823] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyd are optionally substituted with Cj-6 alkoxy;

[0824] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0825] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[0826] In some embodiments, R1is -C1.2 alkylene-N(Rja’)(R3b’) optionally substituted with one or more Rias;43707-02999 / WO (SYND-070 / 001WO)

[0827] each Rlasis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3i)(R3b’), or S(===O)2R3a’;

[0828] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyd are optionally substituted with Cj-6 alkoxy;

[0829] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0830] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0831] In some embodiments, R1is -CH2-N(R3a’)(R3b’) optionally substituted with one or more Rlas;

[0832] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(:=:O)2R3a’;

[0833] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[0834] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0835] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0836] In some embodiments, R1is

[0837]

[0838] -(CH2)2-N(Rja’)(R3b’) optionally substituted with one or more Rlas;

[0839] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0840] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyd are optionally substituted with Cj-6 alkoxy;

[0841] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0842] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[0843] In some embodiments, R1is -(CH2)3-N(R3a’)(R3b’) optionally substituted with one or more Rlas;43707-02999 / WO (SYND-070 / 001WO)

[0844] each Rlasis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3i)(R3b’), or S(===O)2R3a’;

[0845] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Cj-6 alkoxy;

[0846] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0847] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0848] In some embodiments, R1is -(CH2)4-N(R3a’)(R3b’) optionally substituted with one or more Rlas;

[0849] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(:=:O)2R3a’;

[0850] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[0851] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0852] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0853] In some embodiments, R1is

[0854]

[0855] -(CH2)5-N(Rja’)(R3b’) optionally substituted with one or more Rlas;

[0856] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0857] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyd are optionally substituted with Cj-6 alkoxy;

[0858] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0859] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[0860] In some embodiments, R1is -(CH2)6-N(R3a’)(R3b’) optionally substituted with one or more Rlas;43707-02999 / WO (SYND-070 / 001WO)

[0861] each Rlasis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3i)(R3b’), or S(===O)2R3a’;

[0862] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Cj-6 alkoxy;

[0863] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0864] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0865] In some embodiments, R1is -C3-12 cycloalkylene-N(R3a’)(R3b’) optionally substituted with one or ore Rlas;

[0866] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(:=:O)2R3a’;

[0867] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[0868] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0869] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0870] In some embodiments, R1is -C3-11 cycloalkylene-N(R3a’)(R3b’) optionally substituted with one or more Rlas;

[0871] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0872] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyd are optionally substituted with Cj-6 alkoxy;

[0873] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0874] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[0875] In some embodiments, R1is -C3-10 cycloalkylene-N(R3a’)(R3b’) optionally substituted with one or more Rlas;43707-02999 / WO (SYND-070 / 001WO)

[0876] each Rlasis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3i)(R3b’), or S(===O)2R3a’;

[0877] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Cj-6 alkoxy;

[0878] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0879] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0880] In some embodiments, R1is -C3-9 cycloalkylene-N(R3a’)(R3b’) optionally substituted with one or ore Rlas;

[0881] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(:=:O)2R3a’;

[0882] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[0883] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0884] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0885] In some embodiments, Rlis -C3-8 cycloalkylene-N(R3a’)(R3b’) optionally substituted with one or more Rlas;

[0886] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0887] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyd are optionally substituted with Cj-6 alkoxy;

[0888] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0889] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[0890] In some embodiments, R1is -C3-7 cycloalkylene-N(R3a’)(R3b’) optionally substituted with one or more Rlas;43707-02999 / WO (SYND-070 / 001WO)

[0891] each Rlasis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3i)(R3b’), or S(===O)2R3a’;

[0892] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Cj-6 alkoxy;

[0893] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0894] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0895] In some embodiments, R1is -C3-6 cycloalkylene-N(R3a’)(R3b’) optionally substituted with one or ore Rlas;

[0896] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(:=:O)2R3a’;

[0897] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[0898] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0899] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0900] In some embodiments, Rlis -C3-5 cycloalkylene-N(R3a’)(R3b’) optionally substituted with one or more Rlas;

[0901] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0902] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyd are optionally substituted with Cj-6 alkoxy;

[0903] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0904] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[0905] In some embodiments, R1is -C3-4 cycloalkylene-N(R3a’)(R3b’) optionally substituted with one or more Rlas;43707-02999 / WO (SYND-070 / 001WO)

[0906] each Rlasis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3i)(R3b’), or S(===O)2R3a’;

[0907] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Cj-6 alkoxy;

[0908] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0909] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0910] In some embodiments, R1is -C3 cycloalkylene-N(R3a’)(R3b’) optionally substituted with one or ore Rlas;

[0911] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(:=:O)2R3a’;

[0912] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[0913] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0914] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0915] In some embodiments, R1is -C4 cycloalkylene-N(Rja’)(R3b’) optionally substituted with one or more Rlas;

[0916] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0917] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyd are optionally substituted with Cj-6 alkoxy;

[0918] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0919] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[0920] In some embodiments, R1is -C5 cycloalkylene-N(R3a’)(R3b’) optionally substituted with one or more Rlas;43707-02999 / WO (SYND-070 / 001WO)

[0921] each Rlasis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3i)(R3b’), or S(===O)2R3a’;

[0922] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Cj-6 alkoxy;

[0923] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0924] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0925] In some embodiments, R1is -Cg cycloalkylene-N(R3a’)(R3b’) optionally substituted with one or ore Rlas;

[0926] each Rlasis independently halo, oxo, C1-6 alkyl, Ci-g haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(:=:O)2R3a’;

[0927] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[0928] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0929] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0930] In some embodiments, R1is -C7 cycloalkylene-N(Rja’)(R3b’) optionally substituted with one or more Rlas;

[0931] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0932] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyd are optionally substituted with Cj-6 alkoxy;

[0933] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0934] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[0935] In some embodiments, R1is -Cs cycloalkylene-N(R3a’)(R3b’) optionally substituted with one or more Rlas;43707-02999 / WO (SYND-070 / 001WO)

[0936] each Rlasis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3i)(R3b’), or S(===O)2R3a’;

[0937] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Cj-6 alkoxy;

[0938] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0939] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0940] In some embodiments, R1is -C9 cycloalkylene-N(R3a’)(R3b’) optionally substituted with one or ore Rlas;

[0941] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(:=:O)2R3a’;

[0942] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[0943] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0944] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0945] In some embodiments, R1is -C10 cycloalkylene-N(R3a’)(R3b’) optionally substituted with one or more Rlas;

[0946] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0947] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyd are optionally substituted with Cj-6 alkoxy;

[0948] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0949] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[0950] In some embodiments, Rlis -Cn cycloalkylene-N(R'’a’)(R3b’) optionally substituted with one or more Rlas;43707-02999 / WO (SYND-070 / 001WO)

[0951] each Rlasis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3i)(R3b’), or S(===O)2R3a’;

[0952] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Cj-6 alkoxy;

[0953] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0954] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0955] In some embodiments, R1is -C12 cycloalkylene-N(Rja’)(R3b’) optionally substituted with one or ore Rlas;

[0956] each Rlasis independently halo, oxo, Ci-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(:=:O)2R3a’;

[0957] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[0958] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0959] each R3C’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0960] In some embodiments, R1is 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs, and wherein: each Ribsis independently halo, oxo, OR3a’, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a,)(R3b’), or S(=O)2R3a’;

[0961] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0962] each R3b’ is independently H, C1-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0963] each R3c’ is independently H, Cj-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.43707-02999 / WO (SYND-070 / 001WO)

[0964] In some embodiments, R1is 3- to 11-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 11-membered heterocycloalkyl is optionally substituted with one or more Rlbs, and wherein: each Rlbsis independently halo, oxo, OR3a’, Ct-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyd, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a?;

[0965] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3e’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0966] each R3b’ is independently H, Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0967] each R3C’ is independently II, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0968] In some embodiments, R1is 3- to 10-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 10-membered heterocycloalkyl is optionally substituted with one or more Rlbs, and wherein: each Ribsis independently halo, oxo, OR3a’, Cj-6 alkyl, C1-6 haloalkyl, 63-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0969] each R3a’ is independently H, Cj-6 alkyl, 61-6 haloalkyl, C(O)R3c’, 63 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the 61-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with 61-6 alkoxy;

[0970] each R3b’ is independently H, 61-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0971] each R3C?is independently H, Cj-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[0972] In some embodiments, Rlis 3- to 9-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 9-membered heterocycloalkyl is optionally substituted with one or more Rlbs, and wherein: each Ribsis independently halo, oxo, OR3a’, 61-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(::::O)(R3a’), N(R3a’)(R3b’), or S(:::O)2R3a’;

[0973] each R3a’ is independently H, 61-6 alkyl, 61-6 haloalkyl, C(O)R3c’, 63-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12-membered heterocycloalkyd are optionally substituted with 61-6 alkoxy;

[0974] each R3b’ is independently H, 61-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and43707-02999 / WO (SYND-070 / 001WO)

[0975] each R3C’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0976] In some embodiments, Rlis 3- to 8-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 8-membered heterocycloal yl is optionally substituted with one or more Rlbs, and wherein: each Ribsis independently halo, oxo, OR3a’, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(

[0977]

[0978] =O)(R3a?), N(R3a,)(R3b’), or S(=O)2R3a’;

[0979] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0980] each R3b’ is independently H, C1-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0981] each R3c’ is independently H, Cj-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0982] In some embodiments, R1is 3- to 7-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 7- membered heterocycloalkyl is optionally substituted with one or more Rlbs, and wherein: each R!bsis independently halo, oxo, OR3a’, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyd, C(=O)(R3a’), N(R3a’)(Rjb’), or S(=O)2R3a’;

[0983] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-e alkoxy;

[0984] each R3b’ is independently H, Cj-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0985] each R3C’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0986] In some embodiments, R1is 3- to 6-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 6- membered heterocycloalkyl is optionally substituted with one or more Rlbs, and wherein: each Rlbsis independently halo, oxo, OR3a’, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(:::O)(R3a’), N(R3a’)(R3b’), or S(::::O)2R3a’;

[0987] each Rja’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;43707-02999 / WO (SYND-070 / 001WO)

[0988] each R3b’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0989] each R3C’ is independently H, C1-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[0990] In some embodiments, R1is 3- to 5-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 5- membered heterocycloalkyl is optionally substituted with one or more Rlbs, and wherein: each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyd, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a?;

[0991] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3e’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, Cj-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0992] each R3b’ is independently H, Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0993] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[0994] In some embodiments, R1is 3- to 4-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 4-membered heterocycloalkyl is optionally substituted with one or more Rlbs, and wherein: each Ribsis independently halo, oxo, OR3a’, Ci-e alkyl, C1-6 haloalkyl, 63-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a), N(R3a,)(R3b’), or S(=O)2R3a’;

[0995] each R3a’ is independently H, Cj-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, 63-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with 61-6 alkoxy;

[0996] each R3b’ is independently H, 61-6 alkyl, C1- haloalkyl, 63-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[0997] each R3C’ is independently H, Cj-6 alkyl, C1-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[0998] In some embodiments, R1is 3-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3 -membered heterocycloalkyl is optionally substituted with one or more Rlbs, and wherein:

[0999] each Rlbsis independently halo, oxo, OR3a’, 61-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(Rjb’), or S(=O)2R3a’;43707-02999 / WO (SYND-070 / 001WO)

[1000] each Rja’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl, Cj-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1001] each R3b’ is independently H, Cj-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1002] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[1003] In some embodiments, R1is 4-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-membered heterocycloalkyl is optionally substituted with one or more Rlbs, and wherein:

[1004] each Ribsis independently halo, oxo, OR3a’, Ci-e alkyl, C1-6 haloalkyl, 63-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a), N(R3a,)(R3b’), or S(=O)2R3a’;

[1005] each R3a’ is independently H, Cj-6 alkyl, Cue haloalkyl, C(O)R3c’, 63-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the 61-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with 61-6 alkoxy;

[1006] each R3b’ is independently H, 61-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[1007] each R3c’ is independently H, Cj-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[1008] In some embodiments, R1is 5-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 5-menibered heterocycloalkyl is optionally substituted with one or more Rlbs, and wherein:

[1009] each R!bsis independently halo, oxo, OR3a’, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(Rjb’), or S(=O)2R3a’;

[1010] each R3a’ is independently H, 61-6 alkyl, 61-6 haloalkyl, C(O)R3c’, 63-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the 61-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12-membered heterocycloalkyd are optionally substituted with Cj-6 alkoxy;

[1011] each R3b’ is independently H, 61-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[1012] each R3C’ is independently H, 61-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[1013] In some embodiments, R1is 6-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 6-membered heterocycloalkyl is optionally substituted with one or more Rlbs, and wherein:43707-02999 / WO (SYND-070 / 001WO)

[1014] each Rlbsis independently halo, oxo, OR3a’, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(:=:O)(R3a’), N(R3a’)(R3b’), or S(:::O)2R3a’;

[1015] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Cj-6 alkoxy;

[1016] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[1017] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloal yl.

[1018] In some embodiments, R1is 7-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 7-membered heterocycloalkyl is optionally substituted with one or more Rlbs, and wherein:

[1019] each Rlbsis independently halo, oxo, OR3a’, Ct-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyd, C(=O)(R3a’), N(R3a’)(Rjb’), or S(=O)2R3a’;

[1020] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3e’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1021] each R3b’ is independently H, Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[1022] each R3C’ is independently II, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1023] In some embodiments, R1is 8-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 8-membered heterocycloalkyl is optionally substituted with one or more Rlbs, and wherein:

[1024] each Rlbsis independently halo, oxo, OR3a’, Cj-6 alkyl, C1-6 haloalkyl, 63-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[1025] each R3a’ is independently H, Cj-6 alkyl, 61-6 haloalkyl, C(O)R3c’, 63 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the 61-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with 61-6 alkoxy;

[1026] each R3b’ is independently H, 61-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[1027] each R3C’ is independently H, 61-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.43707-02999 / WO (SYND-070 / 001WO)

[1028] In some embodiments, R1is 9-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 9-membered heterocycloalkyl is optionally substituted with one or more Rlbs, and wherein:

[1029] each Rlbsis independently halo, oxo, OR3a’, Ct-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyd, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a?;

[1030] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3e’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1031] each R3b’ is independently H, Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[1032] each R3C’ is independently II, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1033] In some embodiments, R1is 10-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 10-membered heterocycloalkyl is optionally substituted with one or more Rlbs, and wherein:

[1034] each Ribsis independently halo, oxo, OR3a’, Cj-6 alkyl, C1-6 haloalkyl, 63-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[1035] each R3a’ is independently H, Cj-6 alkyl, 61-6 haloalkyl, C(O)R3c’, 63 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the 61-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with 61-6 alkoxy;

[1036] each R3b’ is independently H, 61-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[1037] each R3C?is independently H, Cj-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[1038] In some embodiments, R1is 11 -membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 11 -membered heterocycloalkyl is optionally substituted with one or more Rlbs, and wherein:

[1039] each Ribsis independently halo, oxo, OR3a’, 61-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(::::O)(R3a’), N(R3a’)(R3b’), or S(:::O)2R3a’;

[1040] each R3a’ is independently H, 61-6 alkyl, 61-6 haloalkyl, C(O)R3c’, 63-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12-membered heterocycloalkyd are optionally substituted with 61-6 alkoxy;

[1041] each R3b’ is independently H, 61-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and43707-02999 / WO (SYND-070 / 001WO)

[1042] each R3C’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1043] In some embodiments, R1is 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 12-membered heterocycloal yl is optionally substituted with one or more Rlbs, and wherein:

[1044] each Ribsis independently halo, oxo, OR3a’, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(

[1045]

[1046] =O)(R3a?), N(R3a,)(R3b’), or S(=O)2R3a’;

[1047] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1048] each R3b’ is independently H, C1-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1049] each R3c’ is independently H, Cj-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1050] In some embodiments, R1is C3-12 cycloalkyl substituted with one or more 3- to 12- membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12-membered heterocycloal yl is optionally substituted with one or more Rlcs;

[1051] each Rlcsis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3i)(R3b’), OR3a’, or S(:::O)2R3a’, wherein the Cj-6 alkyl or Ci-6 haloalkyl is optionally substituted with one or more Ci-6 alkoxy;

[1052] each R3a’ is independently H, Cj-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[1053] each R3b’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[1054] each R3C’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[1055] In some embodiments, R1is C3-11 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3.11 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R,cs;43707-02999 / WO (SYND-070 / 001WO)

[1056] each Rlcsis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3i)(R3b’), OR3a’, or S(:::O)2R3a’, wherein the Cj-6 alkyl or Ci-6 haloalkyl is optionally substituted with one or more Ci-6 alkoxy;

[1057] each R3a’ is independently H, Cj-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1058] each R3b’ is independently H, C1-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[1059] each R3c’ is independently H, Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[1060] In some embodiments, R1is C3-10 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the €3-10 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R,cs;

[1061] each Rlesis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the Cj-6 alkyl or Ci-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[1062] each R3a’ is independently H, Cj-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[1063] each R3b’ is independently H, C1-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[1064] each R3c’ is independently H, Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[1065] In some embodiments, R1is C3-9 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-9 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1066] each Rlcsis independently halo, oxo, Ci-6 alkyl, C1-6 haloalkyl, C(:::O)(R3a’), N(R3a,)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or Ci-6 haloalkyl is optionally substituted with one or more Ci-e alkoxy;

[1067] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;43707-02999 / WO (SYND-070 / 001WO)

[1068] each R3b’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1069] each R3C’ is independently H, C1-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[1070] In some embodiments, R1is C3-8 cycloalkyl substituted with one or more 3- to 12- membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-8 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rles;

[1071] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(Rjb’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more Ct-6 alkoxy;

[1072] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyd are optionally substituted with C1-6 alkoxy;

[1073] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[1074] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1075] In some embodiments, R1is C3-7 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-7 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1076] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(Rjb’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more Ci-6 alkoxy;

[1077] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1078] each R3b’ is independently H, C1-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1079] each R3c’ is independently H, Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1080] In some embodiments, R1is C3-6 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other43707-02999 / WO (SYND-070 / 001WO)

[1081] heteroatom ring members; and wherein each of the C3-6 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1082] each R,csis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a', or S(=O)2R3a' wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more Cj-6 alkoxy;

[1083] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3e’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, Cj-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1084] each R3b’ is independently H, Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[1085] each R3C’ is independently II, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1086] In some embodiments, R1is C3-5 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-5 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1087] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b?), OR3a\ or S(=O)2R3a\ wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more Ci-6 alkoxy;

[1088] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-e alkoxy;

[1089] each R3b’ is independently H, Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[1090] each R3c’ is independently H, C1-6 alkyl, C1- haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1091] In some embodiments, R1is C3-4 cycloalkyl substituted with one or more 3- to 12- membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-4 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1092] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(::O)(R3a’), N(R3a’)(R'’b’), OR3aor S(=O)2R3a\ wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;43707-02999 / WO (SYND-070 / 001WO)

[1093] each Rja’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl, Cj-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1094] each R3b’ is independently H, Cj-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1095] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[1096] In some embodiments, R1is cyclopropyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclopropyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1097] each R,csis independently halo, oxo, Ci-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(::::O)2R3a’, wherein the C1-6 alkyl or Ci-6 haloalkyl is optionally substituted with one or more Ci-6 alkoxy;

[1098] each Rja’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3e’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[1099] each R3b’ is independently H, Cj-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[1100] each R3C’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1101] In some embodiments, R1is cyclobutyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclobutyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1102] each Rlcsis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a\ or S(=O)2R3a\ wherein the Ci-6 alkyl or Ci-6 haloalkyl is optionally substituted with one or more Ci-6 alkoxy;

[1103] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-e alkoxy;

[1104] each R3b’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and43707-02999 / WO (SYND-070 / 001WO)

[1105] each R3C’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1106] In some embodiments, R1is cyclopentyl substituted with one or more 3- to 12- membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclopentyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1107] each Rlcsis independently halo, oxo, Cj-6 alkyl, C1- haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more Cj-6 alkoxy;

[1108] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3e’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, Cj-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1109] each R3b’ is independently H, Cj-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1110] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1111] In some embodiments, R1is cyclohexyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclohexyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1112] each R,csis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a', or S(=O)2R3a' wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more Cj-6 alkoxy;

[1113] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3e’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1114] each R3b’ is independently H, Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[1115] each R3C’ is independently II, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1116] In some embodiments, R1is cycloheptyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cycloheptyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;43707-02999 / WO (SYND-070 / 001WO)

[1117] each Rlcsis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3i)(R3b’), OR3a’, or S(:::O)2R3a’, wherein the Cj-6 alkyl or Ci-6 haloalkyl is optionally substituted with one or more Ci-6 alkoxy;

[1118] each R3a’ is independently H, Cj-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1119] each R3b’ is independently H, C1-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[1120] each R3c’ is independently H, Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[1121] In some embodiments, R1is cyclooctyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclooctyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1122] each Rlesis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the Cj-6 alkyl or Ci-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[1123] each R3a’ is independently H, Cj-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[1124] each R3b’ is independently H, C1-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[1125] each R3c’ is independently H, Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[1126] In some embodiments, R1is cyclononyl substituted with one or more 3- to 12- membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclononyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1127] each Rlcsis independently halo, oxo, Ci-6 alkyl, C1-6 haloalkyl, C(:::O)(R3a’), N(R3a,)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or Ci-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[1128] each Rja’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;43707-02999 / WO (SYND-070 / 001WO)

[1129] each R3b’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1130] each R3C’ is independently H, C1-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl.

[1131] In some embodiments, R1is cyclodecyl substituted with one or more 3- to 12- membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclodecyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rles;

[1132] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(Rjb’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more Ct-6 alkoxy;

[1133] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyd are optionally substituted with C1-6 alkoxy;

[1134] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl; and

[1135] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloal yl.

[1136] In some embodiments, R1is C3-12 cycloalkyl substituted with one or more 3- to 12- membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1137] each R!csis independently halo, oxo, Ci-6 alkyl, or C1-6 haloalkyl.

[1138] In some embodiments, R1is C3-11 cycloalkyl substituted with one or more 3- to 12- membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-11 cycloalkyl and the 3- to 12-membered heterocycloal yl is optionally substituted with one or more Rlcs;

[1139] each Rlcsis independently halo, oxo, C1-6 alkyl, or C1-6 haloalkyl.

[1140] In some embodiments, R1is C3-10 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the €3-10 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R,cs;

[1141] each Rlcsis independently halo, oxo, C1-6 alkyl, or C1-6 haloalkyl.43707-02999 / WO (SYND-070 / 001WO)

[1142] In some embodiments, Rlis C3-9 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-9 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1143] each R!csis independently halo, oxo, Ci-6 alkyl, or Ci-6 haloalkyl.

[1144] In some embodiments, R1is C3-8 cycloalkyl substituted with one or more 3- to 12- membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-8 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1145] each Rlcsis independently halo, oxo, Ci-6 alkyl, or C1-6 haloalkyl.

[1146] In some embodiments, R1is C3-7 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-7 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R,cs;

[1147] each Rlcsis independently halo, oxo, Ci-6 alkyl, or C1-6 haloalkyl.

[1148] In some embodiments, R1is C3-6 cycloalkyl substituted with one or more 3- to 12- membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-6 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R,cs;

[1149] each Rlcsis independently halo, oxo, Ci-e alkyl, or C1-6 haloalkyl.

[1150] In some embodiments, R1is C3-5 cycloalkyl substituted with one or more 3- to 12- membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-5 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1151] each Rlcsis independently halo, oxo, Cj-6 alkyl, or C1-6 haloalkyl.

[1152] In some embodiments, R1is C3-4 cycloalkyl substituted with one or more 3- to 12- membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-4 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1153] each Rlesis independently halo, oxo, Ci-6 alkyl, or C1-6 haloalkyl.

[1154] In some embodiments, R1is cyclopropyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclopropyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;43707-02999 / WO (SYND-070 / 001WO)

[1155] each Rlcsis independently halo, oxo, Ci-6 alkyl, or Ci-6 haloalkyl.

[1156] In some embodiments, R1is cyclobutyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclobutyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1157] each Rlcsis independently halo, oxo, Ci-6 alkyl, or Ci-6 haloalkyl.

[1158] In some embodiments, R1is cyclopentyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclopentyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1159] each Rlcsis independently halo, oxo, Ci-e alkyl, or Ci-6 haloalkyl.

[1160] In some embodiments, Rlis cyclohexyl substituted with one or more 3- to 12- membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclohexyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1161] each Rlcsis independently halo, oxo, Cj-6 alkyl, or Ci-6 haloalkyl.

[1162] In some embodiments, R1is cycloheptyl substituted with one or more 3- to 12- membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cycloheptyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1163] each Rlesis independently halo, oxo, Ci-6 alkyl, or Ci-6 haloalkyl.

[1164] In some embodiments, R1is cyclooctyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclooctyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1165] each Rlesis independently halo, oxo, Ci-6 alkyl, or Ci-6 haloalkyl.

[1166] In some embodiments, R1is cyclononyl substituted with one or more 3- to 12- membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclononyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1167] each Rlcsis independently halo, oxo, Ci-6 alkyl, or Ci-6 haloalkyl.

[1168] In some embodiments, R1is cyclodecyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom43707-02999 / WO (SYND-070 / 001WO)

[1169] ring members; and wherein each of the cyclodecyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1170] each Rlesis independently halo, oxo, Ci-6 alkyl, or Ci-6 haloalkyl.

[1171] In some embodiments,

[1172]

[1173] R1is

[1174] In some embodiments.

[1175]

[1176] In some embodiments.

[1177]

[1178] In some embodiments, R

[1179]

[1180] lis, wherein Ring B is a 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted.

[1181] In some embodiments, R

[1182]

[1183] 1is, wherein Ring B is a 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted.43707-02999 / WO (SYND-070 / 001WO)

[1184] " -■ N"..

[1185] k"

[1186] In some embodiments, R

[1187]

[1188] 1is, wherein Ring B is a 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted.

[1189] In some embodiments, R

[1190]

[1191] 1is, wherein Ring B is a 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted, wherein RBnis an optionally substituted Ci-6 alkyl.

[1192] In some embodiments, R

[1193]

[1194] is 'vv’z', wherein Ring B is a 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted, wherein RBnis an optionally substituted Ci-6 alkyl.

[1195] f B 't

[1196] V-c’

[1197] T"

[1198] In some embodiments, R

[1199]

[1200] is, wherein Ring B is a 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted, wherein RBnis an optionally substituted Ci-6 alkyl.

[1201] In some embodiments, RB”is an optionally substituted Ci alkyl.

[1202] In some embodiments, RBnis an optionally substituted C2 alkyl.43707-02999 / WO (SYND-070 / 001WO)

[1203] In some embodiments, RBnis an optionally substituted C3 alkyl.

[1204] In some embodiments, RBnis Cj-6 alkyl optionally substituted with one or more halo. In some embodiments, RBnis Ci alkyl optionally substituted with one or more halo. In some embodiments, RBnis C2 alkyl optionally substituted with one or more halo. In some embodiments, RBnis C3 alkyl optionally substituted with one or more halo. In some embodiments, RBnis a Ci alkyl.

[1205] In some embodiments, RBnis a C2 alkyl.

[1206] In some embodiments, RBnis a C3 alkyl.

[1207] Embodiments covering R2

[1208] In some embodiments, R2is H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C?.

[1209] 6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, or -(3- to 12-membered heterocycloalkyl)-Ci-6 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, Cis alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl )-C 1-6 alkyl, and -(3- to 12-membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from R8;

[1210] each R8is independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, C6-10 aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-6 cycloalkyl, Ci-6 alkoxy, C 1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyd, amino, Ci-6 alkylamino, di(Ci-6 alkyl)amino, thiol, Ci-6 alkylthio, Ci-6 alkylsulfinyl, Cj-6 alkyl sulfonyl, carboxy, aminocarbonyl, Ci s> alkylcarbonyl, and Ci-6 alkoxy carbonyl;

[1211] each R4a’ and R4b’ is independently H, Cis alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1212] each RNIS independently H, Ci-6 alkyl, or Ci-6 haloalkyl.

[1213] In some embodiments, R2is H.

[1214] In some embodiments, R2is Ci-6 alkyl.

[1215] In some embodiments, R2is C1-5 alkyl.

[1216] In some embodiments, R2is C1-4 alkyl.

[1217] In some embodiments, R2is C1-3 alkyl.

[1218] In some embodiments, R2is C1-2 alkyl.

[1219] In some embodiments, R2is methyl.

[1220] In some embodiments, R2is ethyl.43707-02999 / WO (SYND-070 / 001WO)

[1221] In some embodiments, R2is propyl.

[1222] In some embodiments, R2is isopropyl.

[1223] In some embodiments, R2is butyl.

[1224] In some embodiments, R2is tert-butyl.

[1225] In some embodiments, R2is pentyl.

[1226] In some embodiments, R2is hexyl.

[1227] Embodiments covering R1and R2

[1228] In some embodiments, R1and R2form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1229] In some embodiments, R1and R2form a 3- to 11 -membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 3- to 11 -membered heterocycloalkyl is optionally substituted with one or more Cj-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1230] In some embodiments, R1and R2form a 3- to 10-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 3- to 10-membered heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Cj-6 alkoxy.

[1231] In some embodiments, R1and R2form a 3- to 9-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 3- to 9-membered heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1232] In some embodiments, R1and R2form a 3- to 8-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with one or more Cj-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1233] In some embodiments, R1and R2form a 3- to 7-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 3- to 7-membered heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Cj-6 alkoxy.

[1234] In some embodiments, R1and R2form a 3- to 6-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 3- to 6-membered heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1235] In some embodiments, R1and R2form a 3- to 5-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 3- to 5-membered heterocycloalkyl is optionally substituted with one or more Cj-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1236] In some embodiments, R1and R2form a 3- to 4-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 3- to 4-membered heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Cj-6 alkoxy.43707-02999 / WO (SYND-070 / 001WO)

[1237] In some embodiments, R1and R2form a 3 -membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 3-membered heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1238] In some embodiments, R1and R2form a 4-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 4-membered heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1239] In some embodiments, R1and R2form a 5-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 5-membered heterocycloalkyl is optionally substituted with one or more Cj-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1240] In some embodiments, R1and R2form a 6-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 6-membered heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1241] In some embodiments, R1and R2form a 7-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 7-membered heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1242] In some embodiments, R1and R2form a 8-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 8-membered heterocycloalkyl is optionally substituted with one or more Cj-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1243] In some embodiments, R1and R form a 9-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 9-membered heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1244] In some embodiments, R1and R2form a 10-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 10-membered heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1245] In some embodiments, R1and R2form a 11 -membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 11 -membered heterocycloalkyl is optionally substituted with one or more Cj-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1246] In some embodiments, R1and R2form a 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 12-membered heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1247] Embodiments covering R'

[1248] In some embodiments, when m is 0, R3is Ci-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, wherein the Ci-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with one or moreR3as43707-02999 / WO (SYND-070 / 001WO)

[1249] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(==O)2R4b’, or N(R4a)(R4b);

[1250] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1251] each R4bis independently H

[1252]

[1253] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, Cs-i2cycloalkyl, Co-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1254] each R4a’ and R4b’ is independently H, Ci-6 alkyl, Cs-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1255] In some embodiments, when m is 0, R3is Ci-6 alkyl optionally substituted with one or more R3as;

[1256] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, or N(R4a)(R4b);

[1257] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);

[1258] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, Cs-]2cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1259] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -i2cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1260] In some embodiments, when m is 0, R3is C2- alkyd optionally substituted with one or more R3as;

[1261] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4bor N(R4a)(R4b);

[1262] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1263] each R4bis independently H, S(===O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, Cs-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1264] each R4a’ and R4b’ is independently H, C1-6 alkyl, Cs-n cycloalkyl, or 3- to 12-membered heterocycloalkyl.43707-02999 / WO (SYND-070 / 001WO)

[1265] In some embodiments, when m is 0, R3is C1.5 alkyl optionally substituted with one or more R3as;

[1266] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(===O)2R4b’, or N(R4a)(R4b);

[1267] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1268] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloal yl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1269] each R4a’ andR4b’ is independently H, C1-6 alkyl, C 3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1270] In some embodiments, when m is 0, R3is C1-4 alkyl optionally substituted with one or more R3as;

[1271] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, or N(R4a)(R4b);

[1272] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1273] each R4bis independently H, S(=O)2R4b’, C(O)OR4b', C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1274] each R4a’ and R4b?is independently H, C1-6 alkyl, Cs-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1275] In some embodiments, when m is 0, R3is C1-4 alkyl optionally substituted with one or more R3as;

[1276] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, or N(R4a)(R4b);

[1277] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1278] each R4bis independently H

[1279]

[1280] , S(==O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, Cs-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and43707-02999 / WO (SYND-070 / 001WO)

[1281] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1282] In some embodiments, when m is 0, R3is C1-3 alkyl optionally substituted with one or more R3as;

[1283] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, or N(R4a)(R4b);

[1284] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1285] each R4bis independently H

[1286]

[1287] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b?); and

[1288] each R4a’ and R4b’ is independently II, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1289] In some embodiments, when m is 0, R3is Ci-2alkyl optionally substituted with one or more R3as;

[1290] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, or N(R4a)(R4b);

[1291] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1292] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1293] each R4a’ andR4b’ is independently H, Ci-6 alkyl, C 3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1294] In some embodiments, when m is 0, R3is methyl optionally substituted with one or more R3as;

[1295] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b!, or N(R4a)(R4b);

[1296] each R4ais independently H, CN, or C1-6alkyl optionally substituted with one or more halo, C6-10aryl, or N(R4a’)(R4b’);

[1297] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl,43707-02999 / WO (SYND-070 / 001WO)

[1298] or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b;); and

[1299] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1300] In some embodiments, when m is 0, R3is ethyl optionally substituted with one or more R3as;

[1301] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b\ or N(R4a)(R4b);

[1302] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1303] each R4bis independently H, S(===O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1304] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1305] In some embodiments, when ni is 0, R3is C alkyl optionally substituted with one or more R3as;

[1306] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(:=:O)2R4b’, or N(R4a)(R4b);

[1307] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1308] each R4bis independently H

[1309]

[1310] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1311] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1312] In some embodiments, when m is 0, R3is C4 alkyl optionally substituted with one or more R3as;

[1313] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), C, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, or N(R4a)(R4b);

[1314] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);43707-02999 / WO (SYND-070 / 001WO)

[1315] each R4bis independently H, S(=O)2R4b’, C(O)OR4b' C(O)R4b\ C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, Ca-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1316] each R4a’ and R4b?is independently H, Ci-6 alkyl, Cs-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1317] In some embodiments, when m is 0, R3is Cs alkyl optionally substituted with one or more R3as;

[1318] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, or N(R4a)(R4b);

[1319] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1320] each R4bis independently H, S(-O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, Cs-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b?); and

[1321] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1322] In some embodiments, when m is 0, R3is Ce alkyl optionally substituted with one or more R3as;

[1323] each Rjasis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(===O)2R4b’, or N(R4a)(R4b);

[1324] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1325] each R4bis independently

[1326]

[1327] H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1328] each R4a’ and R4b’ is independently H, Ci-6 alkyl, Crn cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1329] In some embodiments, when m is 0, R3is Ct-Ce alkyl substituted with R3as, and wherein Rjasis halo, OR4a, OBn, oxo, or CN.

[1330] In some embodiments, when m is 0, R3is Ci-Ce alkyl substituted with R3as, and wherein R3asis OR4a.43707-02999 / WO (SYND-070 / 001WO)

[1331] In some embodiments, when m is 0, R3is C5 alkyl substituted with OH, OMe, or OBn

[1332] In some embodiments, when m is 0, R3is C5 alkyl substituted with OH or OBn.

[1333] In some embodiments, when m is 0, R3is

[1334]

[1335] In some embodiments, when m is 0, R3is

[1336]

[1337] 0Bn

[1338] In some embodiments, when m is 0, R3is

[1339]

[1340] .

[1341] In some embodiments, R3is Ci-Co alkyl substituted with R3as, and wherein R3asis halo, OR4a, OBn, oxo, or CN.

[1342] In some embodiments, R3is C5 alkyl substituted with OH or OBn.

[1343] In some embodiments, R

[1344]

[1345] 3is OH

[1346] In some embodiments,

[1347]

[1348] R3is °Bn

[1349] In some embodiments, R

[1350]

[1351] 3is

[1352] In some embodiments, when m is 0, R3is C2-6 alkenyl optionally substituted with one or more R3as;

[1353] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, or N(R4a)(R4b);

[1354] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1355] each R4bis independently H

[1356]

[1357] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, Cs-i2cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b?); and

[1358] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.43707-02999 / WO (SYND-070 / 001WO)

[1359] In some embodiments, when m is 0, R3is C2-5 alkenyl optionally substituted with one or more R3as;

[1360] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(===O)2R4b’, or N(R4a)(R4b);

[1361] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1362] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1363] each R4a’ andR4b’ is independently H, C1-6 alkyl, C 3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1364] In some embodiments, when m is 0, R3is C2-4 alkenyl optionally substituted with one or more R3as;

[1365] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, or N(R4a)(R4b);

[1366] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-10aryl, or N(R4a’)(R4b’);

[1367] each R4bis independently H, S(=O)2R4b’, C(O)OR4b', C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1368] each R4a’ and R4b?is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1369] In some embodiments, when m is 0, R3is C2-3 alkenyl optionally substituted with one or more R3as;

[1370] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, or N(R4a)(R4b);

[1371] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1372] each R4bis independently H

[1373]

[1374] , S(==O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and43707-02999 / WO (SYND-070 / 001WO)

[1375] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1376] In some embodiments, when m is 0, R3is C2-6 alkynyl optionally substituted with one or more R3as;

[1377] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, or N(R4a)(R4b);

[1378] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1379] each R4bis independently H

[1380]

[1381] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b?); and

[1382] each R4a’ and R4b’ is independently II, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1383] In some embodiments, when m is 0, R3is C2-5 alkynyl optionally substituted with one or more R3as;

[1384] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, or N(R4a)(R4b);

[1385] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1386] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1387] each R4a’ andR4b’ is independently H, Ci-6 alkyl, C 3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1388] In some embodiments, when m is 0, R3is C2-4 alkynyl optionally substituted with one or more R3as;

[1389] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b!, or N(R4a)(R4b);

[1390] each R4ais independently H, CN, or C1-6alkyl optionally substituted with one or more halo, C6-10aryl, or N(R4a’)(R4b’);

[1391] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl,43707-02999 / WO (SYND-070 / 001WO)

[1392] or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b;); and

[1393] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1394] In some embodiments, when m is 0, R3is C2-3 alkynyl optionally substituted with one or more R3as;

[1395] each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b\ or N(R4a)(R4b);

[1396] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1397] each R4bis independently H, S(===O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1398] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1399] In some embodiments, when ni is 1, R3is H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Co-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Co-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[1400] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-6 alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1401] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1402] each R4bis independently H, S(=O)2R4b’, C(O)OR4b', C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl,43707-02999 / WO (SYND-070 / 001WO)

[1403] or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b;); and

[1404] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1405] In some embodiments, when m is 1, R3is H.

[1406] In some embodiments, when ni is 1, R3is C1-6 alkyl is optionally substituted with one or more R3a;

[1407] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1408] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1409] each R4bis independently H

[1410]

[1411] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b?); and

[1412] each R4a’ and R4b’ is independently II, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1413] In some embodiments, when m is 1, R3is C1-5 alkyd is optionally substituted with one or more R3a;

[1414] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), O

[1415]

[1416] C(O)N(R4a)(R4b), S(===O)2R4b’, N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;43707-02999 / WO (SYND-070 / 001WO)

[1417] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1418] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1419] each R4a’ and R4b’ is independently H, Cj-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1420] In some embodiments, when m is 1, R3is C1-4 alkyl is optionally substituted with one or more R3a;

[1421] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a,)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1422] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1423] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1424] each R4a’ and R4b’ is independently H, C1-6 alkyl, Cs-n cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1425] In some embodiments, when m is 1, R3is C1-3 alkyl is optionally substituted with one or more R3a;

[1426] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(O)2R4b’, N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-10aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’),43707-02999 / WO (SYND-070 / 001WO)

[1427] N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1428] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1429] each R4bis independently H

[1430]

[1431] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1432] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1433] In some embodiments, when ni is 1, R3is C1-2 alkyl is optionally substituted with one or more R3a;

[1434] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, Cs-12 cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1435] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1436] each R4bis independently H

[1437]

[1438] , S(==O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b?); and

[1439] each R4a’ and R4b’ is independently II, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1440] In some embodiments, when m is 1, RJis C2-6 alkenyl is optionally substituted with one or more R3a;

[1441] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), O

[1442]

[1443] C(O)N(R4a)(R4b), S(===O)2R4b’, N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-43707-02999 / WO (SYND-070 / 001WO)

[1444] membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a,)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1445] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1446] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1447] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1448] In some embodiments, when ni is 1, R3is C2-5 alkenyl is optionally substituted with one or more R3a;

[1449] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-10aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a?)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1450] each R4ais independently II, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1451] each R4bis independently H, S(===O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1452] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1453] In some embodiments, when ni is 1, R3is C2-4 alkenyl is optionally substituted with one or more R3a;

[1454] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io43707-02999 / WO (SYND-070 / 001WO)

[1455] aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1456] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1457] each R4bis independently H

[1458]

[1459] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b?); and

[1460] each R4a’ and R4b’ is independently II, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1461] In some embodiments, when m is 1, RJis C2-3 alkenyl is optionally substituted with one or more R3a;

[1462] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), O

[1463]

[1464] C(O)N(R4a)(R4b), S(===O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1465] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1466] each R4bis independently I

[1467]

[1468] I, S(==O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1469] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1470] In some embodiments, when m is 1, R3is C2-6 alkynyl is optionally substituted with one or more R3a;43707-02999 / WO (SYND-070 / 001WO)

[1471] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(O)2R4b’, N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-10aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a?)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1472] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1473] each R4bis independently H, S(===O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1474] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1475] In some embodiments, when m is 1, R is C2-5 alkynyl is optionally substituted with one or more R3a;

[1476] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b?), N(R4a’)(R4b?), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1477] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1478] each R4bis independently H, S(===O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Cj-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1479] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.43707-02999 / WO (SYND-070 / 001WO)

[1480] In some embodiments, when m is 1, R3is C2-4 alkynyl is optionally substituted with one or more R3a;

[1481] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), O

[1482]

[1483] C(O)N(R4a)(R4b), S(===O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1484] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1485] each R4bis independently H

[1486]

[1487] , S(==O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1488] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1489] In some embodiments, when m is 1, R3is C2-3 alkynyl is optionally substituted with one or more R3a;

[1490] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b', N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-10aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a,)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1491] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1492] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and43707-02999 / WO (SYND-070 / 001WO)

[1493] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1494] In some embodiments, when m is 1, R3is C1-6 alkoxy is optionally substituted with one or more R3a;

[1495] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b?), N(R4a’)(R4b?), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1496] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-10aryl, or N(R4a’)(R4b’);

[1497] each R4bis independently H, S(=O)2R4b’, C(O)OR4b', C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1498] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1499] In some embodiments, when m is 1, R3is C1-5 alkoxy is optionally substituted with one or more R3a;

[1500] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6 alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1501] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1502] each R4bis independently H, S(=O)2R4b’, C(O)OR4b', C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl,43707-02999 / WO (SYND-070 / 001WO)

[1503] or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b;); and

[1504] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1505] In some embodiments, when m is 1, R3is Cj-4 alkoxy is optionally substituted with one or more R3a;

[1506] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloal kyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a,)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1507] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1508] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1509] each R4a’ and R4b’ is independently H, Cj-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1510] In some embodiments, when m is 1, R3is Cj-3 alkoxy is optionally substituted with one or more R3a;

[1511] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-w aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR43’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a,)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1512] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);43707-02999 / WO (SYND-070 / 001WO)

[1513] each R4bis independently H, S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1514] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1515] In some embodiments, when m is 1, R3is Ci-2alkoxy optionally substituted with one or more R3a, wherein:

[1516] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-i2cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-i2cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1517] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1518] each R4bis independently H

[1519]

[1520] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-i2cycloalkyl, Co-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1521] each R4a’ and R4b’ is independently II, Ci-6 alkyl, C3-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1522] In some embodiments, when m is 1, R3is C3-i2cycloalkyl optionally substituted with one or more R3a, wherein:

[1523] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6 alkyl, C3-12cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-i2cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1524] 10:43707-02999 / WO (SYND-070 / 001WO)

[1525] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1526] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1527] each R4a’ and R4b’ is independently H, Cj-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1528] In some embodiments, when m is 1, R3is C3.11 cycloalkyl optionally substituted with one or more R3a, wherein:

[1529] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-w aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a,)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1530] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1531] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1532] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1533] In some embodiments, when m is 1, R3is C3-10 cycloalkyl optionally substituted with one or more R3a, wherein:

[1534] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(O)2R4b’, N(R4a)(R4b), Cn6alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’),43707-02999 / WO (SYND-070 / 001WO)

[1535] N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1536] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1537] each R4bis independently H

[1538]

[1539] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1540] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1541] In some embodiments, when m is 1, R3is C3-9 cycloalkyl optionally substituted with one or more R3a, wherein:

[1542] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1543] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1544] each R4bis independently H

[1545]

[1546] , S(==O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b?); and

[1547] each R4a’ and R4b’ is independently II, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1548] In some embodiments, when m is 1, R3is C3-8 cycloalkyl optionally substituted with one or more R3a, wherein:

[1549] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), O

[1550]

[1551] C(O)N(R4a)(R4b), S(===O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-43707-02999 / WO (SYND-070 / 001WO)

[1552] membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a,)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1553] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1554] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1555] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1556] In some embodiments, when m is 1, RJis C3-7 cycloalkyl optionally substituted with one or more R3a, wherein:

[1557] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(O)2R4b’, N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-10aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a?)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1558] each R4ais independently II, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1559] each R4bis independently H, S(===O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1560] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1561] In some embodiments, when m is 1, RJis C3-6 cycloalkyl optionally substituted with one or more R3a, wherein:

[1562] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io43707-02999 / WO (SYND-070 / 001WO)

[1563] aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1564] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1565] each R4bis independently H

[1566]

[1567] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b?); and

[1568] each R4a’ and R4b’ is independently II, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1569] In some embodiments, when ni is 1, R3is C3-5 cycloalkyl optionally substituted with one or more R3a, wherein:

[1570] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), O

[1571]

[1572] C(O)N(R4a)(R4b), S(===O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1573] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1574] each R4bis independently H

[1575]

[1576] , S(==O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1577] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1578] In some embodiments, when ni is 1, R3is C3-1 cycloalkyl optionally substituted with one or more R3a, wherein:43707-02999 / WO (SYND-070 / 001WO)

[1579] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(O)2R4b’, N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-10aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a,)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1580] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1581] each R4bis independently H, S(===O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1582] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1583] In some embodiments, when m is 1, R3is Ce-io aryl optionally substituted with one or more R3a, wherein:

[1584] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b?), N(R4a’)(R4b?), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1585] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io and, or N(R4a’)(R4b’);

[1586] each R4bis independently H, S(===O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Cj-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1587] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.43707-02999 / WO (SYND-070 / 001WO)

[1588] In some embodiments, when m is 1, R3is Ce-9 aryl optionally substituted with one or more R3a, wherein:

[1589] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), O

[1590]

[1591] C(O)N(R4a)(R4b), S(===O)2R4b’, N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1592] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1593] each R4bis independently H

[1594]

[1595] , S(==O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1596] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1597] In some embodiments, when m is 1, R3is Ce-8 aryl optionally substituted with one or more R3a, wherein:

[1598] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b', N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-10aryl, 3- to 12-membered heterocycloal kyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a,)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1599] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1600] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and43707-02999 / WO (SYND-070 / 001WO)

[1601] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1602] In some embodiments, when m is 1, R3is Ce-7 aryl optionally substituted with one or more R3a, wherein:

[1603] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b?), N(R4a’)(R4b?), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1604] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-10aryl, or N(R4a’)(R4b’);

[1605] each R4bis independently H, S(=O)2R4b’, C(O)OR4b', C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1606] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1607] In some embodiments, when m is 1, R3is phenyl optionally substituted with one or more R3a, wherein:

[1608] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6 alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1609] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1610] each R4bis independently H, S(=O)2R4b’, C(O)OR4b', C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl,43707-02999 / WO (SYND-070 / 001WO)

[1611] or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b;); and

[1612] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1613] In some embodiments, when m is 1, R3is 5- to 10-membered heteroaryl optionally substituted with one or more R3a, wherein:

[1614] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a,)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1615] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1616] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1617] each R4a’ and R4b’ is independently H, Cj-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1618] In some embodiments, when m is 1, R3is 5- to 9-membered heteroaryl optionally substituted with one or more R3a, wherein:

[1619] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-w aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR43’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a,)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1620] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1621] no43707-02999 / WO (SYND-070 / 001WO)

[1622] each R4bis independently H, S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-i2cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1623] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1624] In some embodiments, when m is 1, R3is 5- to 8-membered heteroaryl optionally substituted with one or more R3a, wherein:

[1625] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-i2cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-i2cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1626] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1627] each R4bis independently H

[1628]

[1629] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-i2cycloalkyl, Co-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1630] each R4a’ and R4b’ is independently II, Ci-6 alkyl, C3-i2cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1631] In some embodiments, when m is 1, R3is 5- to 7-membered heteroaryl optionally substituted with one or more R3a, wherein:

[1632] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6 alkyl, C3-]2cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-i2cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;43707-02999 / WO (SYND-070 / 001WO)

[1633] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1634] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1635] each R4a’ and R4b’ is independently H, Cj-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1636] In some embodiments, when m is 1, R3is 5- to 6-membered heteroaryl optionally substituted with one or more R3a, wherein:

[1637] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a,)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1638] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1639] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1640] each R4a’ and R4b’ is independently H, C1-6 alkyl, Cs-n cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1641] In some embodiments, when m is 1, R3is 3- to 12-membered heterocycloalkyl optionally substituted with one or more R3a, wherein:

[1642] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(O)2R4b’, N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-10aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’),43707-02999 / WO (SYND-070 / 001WO)

[1643] N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1644] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1645] each R4bis independently H

[1646]

[1647] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1648] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1649] In some embodiments, when m is 1, R3is 3- to 11-membered heterocycloalkyl optionally substituted with one or more R3a, wherein:

[1650] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1651] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1652] each R4bis independently H

[1653]

[1654] , S(==O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b?); and

[1655] each R4a’ and R4b’ is independently II, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1656] In some embodiments, when m is 1, R3is 3- to 10-membered heterocycloalkyl optionally substituted with one or more R3a, wherein:

[1657] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), O

[1658]

[1659] C(O)N(R4a)(R4b), S(===O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-43707-02999 / WO (SYND-070 / 001WO)

[1660] membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a,)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1661] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1662] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1663] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1664] In some embodiments, when m is 1, RJis 3- to 9-membered heterocycloalkyl optionally substituted with one or more R3a, wherein:

[1665] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(O)2R4b’, N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-10aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a?)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1666] each R4ais independently II, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1667] each R4bis independently H, S(===O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1668] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1669] In some embodiments, when m is 1, RJis 3- to 8-membered heterocycloalkyl optionally substituted with one or more R3a, wherein:

[1670] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io43707-02999 / WO (SYND-070 / 001WO)

[1671] aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1672] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1673] each R4bis independently H

[1674]

[1675] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b?); and

[1676] each R4a’ and R4b’ is independently II, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1677] In some embodiments, when m is 1, R3is 3- to 7-membered heterocycloalkyl optionally substituted with one or more R3a, wherein:

[1678] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), O

[1679]

[1680] C(O)N(R4a)(R4b), S(===O)2R4b’, N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1681] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1682] each R4bis independently H

[1683]

[1684] , S(==O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1685] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1686] In some embodiments, when m is 1, R3is 3- to 6-membered heterocycloalkyl optionally substituted with one or more R3a, wherein:43707-02999 / WO (SYND-070 / 001WO)

[1687] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(O)2R4b’, N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-10aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a,)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1688] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1689] each R4bis independently H, S(===O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1690] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1691] In some embodiments, when m is 1, RJis 3- to 5-membered heterocycloalkyl optionally substituted with one or more R3a, wherein:

[1692] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b?), N(R4a’)(R4b?), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1693] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io and, or N(R4a’)(R4b’);

[1694] each R4bis independently H, S(===O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Cj-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1695] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.43707-02999 / WO (SYND-070 / 001WO)

[1696] In some embodiments, when m is 1, R3is 3- to 4-membered heterocycloalkyl optionally substituted with one or more R3a, wherein:

[1697] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), O

[1698]

[1699] C(O)N(R4a)(R4b), S(===O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1700] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1701] each R4bis independently H

[1702]

[1703] , S(==O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1704] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloal yl.

[1705] In some embodiments, when m is 1, R3is C(O)(R4a), wherein:

[1706] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’); and

[1707] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1708] In some embodiments, when m is 1, R3is C(O)O-C(R4a)2-OC(O)(R4a), wherein: each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’); and

[1709] each R4a’ and R4b’ is independently I I, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1710] In some embodiments, when m is 1, R3forms a 3- to 12-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more R3a;

[1711] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-643707-02999 / WO (SYND-070 / 001WO)

[1712] alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a,)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1713] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);

[1714] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1715] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1716] In some embodiments, when m is 1, R3forms a 3- to 11-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 11-membered heterocycloalkyl is optionally substituted with one or more R3a, wherein:

[1717] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-6 alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyd that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1718] each R4ais independently H, CN, or C1- alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1719] each R4bis independently H

[1720]

[1721] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b?); and

[1722] each R4a’ and R411’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.43707-02999 / WO (SYND-070 / 001WO)

[1723] In some embodiments, when m is 1, R3forms a 3- to 10-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 10-membered heterocycloalkyl is optionally substituted with one or more R3a, wherein:

[1724] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1725] each R4ais independently H, CN, or C1-6alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1726] each R4bis independently H, S(=O)2R4b’, C(O)OR4b', C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1727] each R4a’ and R4b?is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1728] In some embodiments, when m is I, R3forms a 3- to 9-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 9-membered heterocycloalkyl is optionally substituted with one or more R3a, wherein:

[1729] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1730] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1731] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl,43707-02999 / WO (SYND-070 / 001WO)

[1732] or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b;); and

[1733] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1734] In some embodiments, when m is 1, R3forms a 3- to 8-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with one or more R3a, wherein:

[1735] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1736] each R4ais independently H, CN, or C1- alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1737] each R4bis independently H

[1738]

[1739] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b?); and

[1740] each R4a’ and R4b’ is independently II, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1741] In some embodiments, when m is 1, R3forms a 3- to 7-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 7-membered heterocycloalkyl is optionally substituted with one or more R3a, wherein:

[1742] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b?), N(R4a’)(R4b?), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;43707-02999 / WO (SYND-070 / 001WO)

[1743] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1744] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1745] each R4a’ andR4b’ is independently H, C'i- alkyl, C 3.12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1746] In some embodiments, when m is 1, R3forms a 3- to 6-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 6-membered heterocycloalkyl is optionally substituted with one or more R3a, wherein:

[1747] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), O

[1748]

[1749] C(O)N(R4a)(R4b), S(===O)2R4b’, N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyd that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1750] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1751] each R4bis independently H

[1752]

[1753] , S(==O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1754] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1755] In some embodiments, when m is 1, R3forms a 3- to 5-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 5-membered heterocycloalkyl is optionally substituted with one or more R3a, wherein:

[1756] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-43707-02999 / WO (SYND-070 / 001WO)

[1757] membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a,)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1758] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1759] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1760] each R4a’ andR4b’ is independently II, C1-6 alkyl, C 3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1761] In some embodiments, when m is 1, R3forms a 3- to 4-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 4- membered heterocycloalkyl is optionally substituted with one or more R3a, wherein:

[1762] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b', N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-10aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a?)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1763] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);

[1764] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1765] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1766] In some embodiments, when m is 1, R3forms a 3-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3 -membered heterocycloalkyl is optionally substituted with one or more R3a, wherein:43707-02999 / WO (SYND-070 / 001WO)

[1767] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(O)2R4b’, N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-10aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a,)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1768] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1769] each R4bis independently H, S(===O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1770] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1771] In some embodiments, when m is 1, R3forms a 4-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 4-membered heterocycloalkyl is optionally substituted with one or more R3a, wherein:

[1772] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloal kyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a,)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1773] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1774] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and43707-02999 / WO (SYND-070 / 001WO)

[1775] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1776] In some embodiments, when m is 1, R3forms a 5-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 5-membered heterocycloalkyl is optionally substituted with one or more R3a, wherein:

[1777] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a,)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1778] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1779] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1780] each R4a’ andR4b’ is independently H, C1-6 alkyl, C 3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1781] In some embodiments, when m is 1, R3forms a 6-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 6-membered heterocycloalkyl is optionally substituted with one or more R3a, wherein:

[1782] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b', N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-10aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a,)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1783] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-10 aryl, or N(R4a’)(R4b’);43707-02999 / WO (SYND-070 / 001WO)

[1784] each R4bis independently H, S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1785] each R4a’ and R4b?is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1786] In some embodiments, when m is 1, R3forms a 7-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 7 -membered heterocycloalkyl is optionally substituted with one or more R3a, wherein:

[1787] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(::::O)2R4b’, N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-10aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-10 aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’ )C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1788] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1789] each R4bis independently H, S(===O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Cj-6 alkyl is optionally substituted with Cj-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1790] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1791] In some embodiments, when m is 1, R3forms a 8-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 8-membered heterocycloalkyl is optionally substituted with one or more R3a, wherein:

[1792] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-6 alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloal kyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a,)(R4b’), N(R4a’)(R4b’),43707-02999 / WO (SYND-070 / 001WO)

[1793] N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1794] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1795] each R4bis independently H

[1796]

[1797] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1798] each R4a’ and R4b?is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1799] In some embodiments, when m is 1, R3forms a 9-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 9-membered heterocycloalkyl is optionally substituted with one or more R3a, wherein:

[1800] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b?), N(R4a’)(R4b?), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1801] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-10aryl, or N(R4a’)(R4b’);

[1802] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Cj-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1803] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1804] In some embodiments, when m is 1, R3forms a 10-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 10-membered heterocycloalkyl is optionally substituted with one or more R3a, wherein:

[1805] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-6alkyl, C3-12cycloalkyl, C1-6alkoxy, C6-1043707-02999 / WO (SYND-070 / 001WO)

[1806] aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), C1-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1807] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1808] each R4bis independently H

[1809]

[1810] , S(=O)2R4b’, C(O)OR4b' C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b?); and

[1811] each R4a’ and R4b’ is independently II, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1812] In some embodiments, when m is 1, R3forms a 11 -membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 11 -membered heterocycloalkyl is optionally substituted with one or more R3a, wherein:

[1813] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1814] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-10aryl, or N(R4a’)(R4b’);

[1815] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1816] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.43707-02999 / WO (SYND-070 / 001WO)

[1817] In some embodiments, when m is 1, R3forms a 12-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 12-membered heterocycloalkyl is optionally substituted with one or more R3a, wherein:

[1818] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C3-12 cycloalkyl, Cj-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10- membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1819] each R4ais independently H, CN, or C1-6alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1820] each R4bis independently H, S(=O)2R4b’, C(O)OR4b', C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1821] each R4a’ and R4b?is independently H, C1-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1822] Embodiments covering m

[1823] In some embodiments, m is 0.

[1824] In some embodiments, m is 1.

[1825] Embodiments covering n

[1826] In some embodiments, n is 1.

[1827] In some embodiments, n is 2.

[1828] In some embodiments, n is 3.

[1829] Exemplary Combinations43707-02999 / WO (SYND-070 / 001WO)

[1830] In some embodiments, V

[1831]

[1832] is CH, Y is N, and R1is

[1833] In some embodiments, V

[1834]

[1835] is CH, Y is N, R1is, and R2is isopropyl.

[1836] In some embodiments, Vis CH, Y is N, R1is and R3is

[1837]

[1838] In some embodiments, V

[1839]

[1840] is CH, Y is N, Rlis

[1841] In some embodiments, V is CH, Y is N, R1is, R2is isopropyl, and R3is

[1842]

[1843] OH, '1%1- OMe;or OBn43707-02999 / WO (SYND-070 / 001WO)

[1844] In some embodiments, V is CH, Y is N, R1is, R2is isopropyl, and R3is

[1845]

[1846] or In some embodiments, the compound is of Formula I, II, or III combined with any of the embodiments described herein.

[1847] Any of the groups described above for any variable can be combined with any of the other groups described above, where applicable, for any of the Formulae described herein Representative compounds of the present disclosure are shown in the table below.43707-02999 / WO (SYND-070 / 001WO)

[1848] Table 1. Representative Compounds of the Present Disclosure

[1849] Compound

[1850] Structure IUPAC Name

[1851] No.

[1852] o -Y

[1853] — N /

[1854] 2-((4-(2-(l-(Benzylox}')-3-meth}4butan- / I Ti - Z y i.,

[1855] z '\ \ 2-yl)-2,6-diazaspiro[3.4]octan-6- 1 y l)py rimi din - 5 -y I )oxy )- 5 -fluoro-7v- V Y o'Y° V i sopropyl-A-(( 1 r, 3r)-3 -methyl-3 - Y,c oc _ / Y (pyrrolidin- 1 -yl)cy clobutyl)benzamide O 11 z

[1856] F N

[1857] V''z'iL

[1858] J 5-Fluoro-2-((4-(2-( 1 -hydroxy-3- methylbutan-2-yl)-2,6- T I diazaspi ro [3.4] octan -6 -y 1 )py rimi din - 5 - 2 O[185...

Claims

1. 43707-02999 / WO (S YND-070 / 001 WO)CLAIMSWhat is claimed is:

1. A compound of Formula I:a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:V is N or CH;Y is N or CH;wherein e and f indicate points of attachment to the remainder of the molecule;R1is(a) Ci-6haloalkyl, Ci-e alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, 5- to 10- membered heteroaryl, C3- 12 cycloalkyl, 3- to 12-membered heterocycloalkyl, -Cs-ioaryl- Ci-6 alkyl, -C3-i2Cycloalkyl-Ct-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, or -(4- to 10-membered heterocycloalkyl)-Ci-6 alkyl, wherein said Cuehaloalkyl, C1-6 alkoxy, C2- 6 alkenyl, C2-6 alkynyl, Ce-ioaryl, 5- to 10-membered heteroaryl, C3- 12 cycloalkyl, 3- to 12-membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Cj-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, and -(4- to 10-membered heterocycloalkyl)-Ci-643707-02999 / WO (S YND-070 / 001 WO)alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;(b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;each Rlsis independently oxo or =NR4a;(c) -Ci-6 alkylene-N(R3a’)(Rjb’) or -63-12 cycloalkylene-N(R3a’)(R3b’), wherein the Ct-6 alkylene or 63-12 cycloalkylene is optionally substituted with one or more Rlas;each Rlasis independently halo, oxo, Ci-e alkyl, C1-6 haloalkyl, C(=O)(Rja’), N(R3a’)(R3b’), or S(=O)2R3a’;(d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;each Rlbsis independently halo, oxo, OR3a’, Ci-6 alkyl, Cj-6 haloalkyl, 63-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(:::O)(R3a’), N(R3a’)(R3b,), or S(===O)2R3a’; or(e) 63-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the 63-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;each Rlcsis independently halo, oxo, 61-6 alkyl, 61-6 haloalkyl, C(::::O)(R3a’), N(R3a’)(R3b), OR3a’, or S(=O)2R3a’, wherein the 61-6 alkyl or 61-6 haloalkyl is optionally substituted with one or more 61-6 alkoxy;each R3a’ is independently H, 61-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, 63-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the 61-6 alkyl, 64-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with 61-6 alkoxy;each R3b’ is independently H, 61-6 alkyl, Ci-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;each R3C’ is independently H, 61-6 alkyl, 61-6 haloalkyl, 63-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;43707-02999 / WO (S YND-070 / 001 WO)R2is H, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5- to 1 O-membered heteroaryl, 3- to 12-membered heterocycloalkyl, -C6-ioaryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, or -(3- to 12-membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, -Ce-toaryl-Ci-e alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, and -(3- to 12-membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rs; or R1and R2form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;each R8is independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, Cj-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, Cue haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, Cue alkylamino, di(Cj-6alkyl)amino, thiol, Cj -6 alkylthio, Ci-6 alkylsulfinyl, Ci-6 alkylsulfonyl, carboxy, aminocarbonyl, Ci-6 alkyl carbonyl, and C 1-6 alkoxy carbonyl;Ring A is 6- to 10-membered aryl or 5- to 10-membered heteroaryl, wherein the 6- to 10- membered aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more Cj-6 alkyl, halo, OH, CN, or Cue alkoxy;X3is H or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocycloalkyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b);when m is 0:R3is Ci-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, wherein the Ci-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with one or more R3as;each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b\ or N(R4a)(R4b);when m is 1:R3is H, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-1243707-02999 / WO (S YND-070 / 001 WO)cycloalkyl, Cg-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a, orR3forms a 3- to 12-membered heterocycloalkyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, C6-io aryl, 3-to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R43’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;each R4ais independently II, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);each R4bis independently H, S(-O)2R4b’, C(O)OR4b’, C(O)R4b’ C(O)NR4a’R4b’, C(O)CH2-N(R4a,)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Cg-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Cj-6 alkoxy or C(O)N(R4a’)(R4b’);each R4a’ and R4b’ is independently II, Ci-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;each Rxis independently H, Ci-6 alkyl, or Ci-6 haloalkyl;m is 0 or 1; andn is 1, 2, or 3;wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

2. A compound of Formula II:43707-02999 / WO (S YND-070 / 001 WO)R3Formula II,a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:V is N or CH;Y is N or CH;R1is(a) C i-6 haloalky 1, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Cs-ioaryl, 5- to 10- membered heteroaryl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, -Ce-ioaryl-Cj-6 alkyl, -C3-12 cycloalkyl-Cj-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, or -(4- to 10-membered heterocycloalkyl)-Ci-6 alkyl, wherein said Ci-ehaloalkyl, Ci-6 alkoxy, C2- 6 alkenyl, C2-6 alkynyl, Ce-ioaryl, 5- to 10-membered heteroaryl, C3- 12 cycloalkyl, 3- to 12-membered heterocycloalkyl, -Cs-io aryl-Ci-6 alkyl, -C3-12 cycloalky l-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, and -(4- to 10-membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rs;(b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two R,s;each R,sis independently oxo or =NR4a;(c) -Ci-6 alkylene-N(R3a’)(Rjb’) or -C3-12 cycloalkylene-M(R3a’)(R3b’), wherein the Ci-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more R,as;each Rlasis independently halo, oxo, Ci-6 alkyl, Ci-6 haloaikyl, C(=O)(Rja’), N(R3a’)(R3b’), or S(=O)2R3a’;43707-02999 / WO (S YND-070 / 001 WO)(d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;each Rlbsis independently halo, oxo, OR3a’, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or(e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloal kyl is optionally substituted with one or more Rlcs;each Rlcsis independently halo, oxo, Ci-e alkyl, C1-6 haloalkyl, C(=O)(Rja’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the Ci-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more Ci-e alkoxy;eachR3a’ is independently H, Cj-6 alkyl, Cj-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, Cj-6 haloalkyl, €3.12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Cj-6 alkoxy;each R3b’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl;each R3C’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12- membered heterocycloalkyl;R2is H, Ci-6 alkyl, Cj -6 haloalkyl, Cj-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, -Cg-ioaryl-Ci-e alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, or -(3- to 12- membered heterocycloalkyl)-Ci-6 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5- to 10-membered heteroaryl, 3- to 12- membered heterocycloalkyl, -Ce-ioaryl-Ci-e alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5- to 10-membered heteroaryl)-Ci-6 alkyl, and -(3- to 12-membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;43707-02999 / WO (S YND-070 / 001 WO)each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN), C1-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C 1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6alkyl)ammo, thiol, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aniinocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxy carbonyl;R3is C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, wherein the C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with one or more R3as;each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, or N(R4a)(R4b);each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-io ar>d, or N(R4a’)(R4b’);each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with Cj-6 alkoxy or C(O)N(R4a’)(R4b’);each R4a’ and R4b’ is independently H, Cj-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; andeach RN is independently H, C1-6 alkyl, or Cj-6 haloalkyl;wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

3. A compound of Formula HI:Formula III, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:43707-02999 / WO (S YND-070 / 001 WO)Rlis C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;eachicsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more Cj-6 alkoxy;each R3a’ is independently H, Cj-6 alkyl, Cj-6 haloalkyl, C(O)R3e’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, Cj-6 haloalkyl, €3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Cj-6 alkoxy;each Rjb’ is independently H, C1-6 alkyl, Ci-e haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;each R3C’ is independently H, Ci-e alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;R2is H, C1-6 alkyl, Cj -6 haloalkyl, Cj-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, -Ce-ioaryl-Cne alkyl, -C3-12 cy cl oalkyl-C 1-6 alkyl, -(5- to 10-membered heteroaryl)-Ci^> alkyl, or -(3- to 12-membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, Cj-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5- to I O-membered heteroaryl, 3- to 12- membered heterocycloalkyl, -Ce-ioaryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5- to 10- membered heteroaryl)-Ci-6 alkyl, and -(3- to 12-membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;each Rgis independently selected from OH, NO2, CM, halo, oxo, OBn, N(RN)2, C1-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C 1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C1-6 alkylthio, C1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C 1-6 alkoxy carbonyl;R3is Ci-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, wherein the C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with one or more R3as;each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, or N(R4a)(R4b);43707-02999 / WO (S YND-070 / 001 WO)each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’);each R4a’ and R4b’ is independently H, Ct-6 alkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; andeach M is independently H, C1-6 alkyl, or C1-6 haloalkyl.

4. The compound of claim 1 or claim 2, wherein V is N.

5. The compound of claim 1 or claim 2, wherein V is CH,6. The compound of claim 1 or claim 2, wherein Y is N.

7. The compound of claim 1 or claim 2, wherein Y is CH8. The compound of any one of claims 1-7, wherein R1is C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3-to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;each Rlcsis independently halo, oxo, C1-6 alkyl, or Ci-6 haloalkyl.

9. The compound of any one of claims 1-8, wherein R1is, wherein Ring B is a 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted.43707-02999 / WO (S YND-070 / 001 WO)10. The compound of any one of claims 1-9, wherein R1is, wherein Ring B is a 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted.

11. The compound of any one of claims 1-9, wherein R1is, wherein Ring B is a 3-to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted.

12. The compound of any one of claims 1 -9, whereinR1is13. The compound of claim 12, wherein R1is14. The compound of any one of claims 1-13, wherein R2is Ci-6 alkyl.

15. The compound of claim 14, wherein R2is isopropyl.43707-02999 / WO (S YND-070 / 001 WO)16. The compound of any one of claims 1-15, wherein m is 0.

17. The compound of any one of claims 1-15, wherein m is 1.

18. The compound of any one of claims 1 -17, wherein n is 1.

19. The compound of any one of claims 1-17, wherein n is 2.

20. The compound of any one of claims 1-17, wherein n is 3.

21. The compound of claim 1, wherein Ring A is 6- to 10-membered aryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

22. The compound of claim 21, wherein Ring A is 6- to 10-membered aryl,23. The compound of claim 1, wherein Ring A is 5- to 10-membered heteroaryl optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

24. The compound of claim 23, wherein Ring A is 5- to 10-membered heteroaryl.

25. The compound of any one of claims I -24, wherein X3is H or Ci-6 alkyl.

26. The compound of any one of claims 1 -25, wherein R3is Ci-6 alkyl optionally substituted with one or more R3as, and wherein:each R3asis independently halo, OR4a, OBn, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(==O)2R4b’, or N(R4a)(R4b);each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);each R4bis independently H, S(-O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Cg-io aryl, 5- to 10-membered heteroaryl, or43707-02999 / WO (S YND-070 / 001 WO)3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); andeach R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.27, The compound of any one of claims 1-26, wherein R3is Ci-Ce alkyl substituted with Rjas, and wherein R3asis halo, OR4a, OBn, oxo, or CN.

28. The compound of claim 27, wherein R3is ('5 alkyl substituted with OH or OBn.

29. The compound of claim 28, wherein R330. The compound of claim 28, wherein R331. The compound of claim 27, wherein R332. A compound as shown in Table 1 or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

33. A compound as shown in Table 1 or a pharmaceutically acceptable salt thereof.

34. A compound as shown in Table 1.

35. A compound as shown in Table 1 or a pharmaceutically acceptable salt thereof, wherein the salt is hydrochloride.43707-02999 / WO (S YND-070 / 001 WO)36. The compound of any one of claims 1 -35, wherein the compound is useful for the treatment of cancer and wherein the compound minimizes IrERG binding.

37. A pharmaceutical composition comprising a compound of any one of claims 1-36, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable earner.

38. A pharmaceutical composition comprising a salt or crystalline form of the compound of any one of claims 1 -36, and at least one pharmaceutically acceptable carrier.

39. A method of inhibiting the interaction between menin and MIT comprising contacting the menin and MIT with a compound of any one of claims 1-36 or a pharmaceutical composition of claim 37 or claim 38.

40. A method of treating cancer in a patient comprising administering to the patient a compound of any one of claims 1-36 or a pharmaceutical composition of claim 37 or claim 38.

41. The method of claim 40, wherein the cancer is a hematological cancer.

42. The method of claim 40, wherein the cancer is a leukemia.

43. The method of claim 40, wherein the cancer is a lymphoma.

44. The method of claim 40, wherein the cancer is mixed lineage leukemia (MLL), MLL-related leukemia, MLL-associated leukemia, MLL-positive leukemia, MLL-induced leukemia, rearranged mixed lineage (KMT2A-rearranged) leukemia (MLL-r), leukemia associated with a MLL rearrangement or a rearrangement of the MLL gene, acute leukemia, chronic leukemia, indolent leukemia, lymphoblastic leukemia, lymphocytic leukemia, myeloid leukemia, myelogenous leukemia, childhood leukemia, acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), acute granulocytic leukemia, acute nonlymphocytic leukemia, chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), therapy related leukemia, myelodysplastic syndrome (MDS), myeloproliferative disease (MPD), myeloproliferative43707-02999 / WO (S YND-070 / 001 WO)neoplasia (MPN), plasma cell neoplasm, multiple myeloma, myelodysplasia, cutaneous T-cell lymphoma, lymphoid neoplasm, AIDS-related lymphoma, thymoma, thymic carcinoma, mycosis fungoides, Alibert-Bazin syndrome, granuloma fungoides, Sezary Syndrome, hairy cell leukemia, T-cell proiymphocytic leukemia (T-PLL), large granular lymphocytic leukemia, meningeal leukemia, leukemic leptomeningitis, leukemic meningitis, multiple myeloma, Hodgkin's lymphoma, non Hodgkin's lymphoma (malignant lymphoma), or Waldenstrom's macroglobulinemia,45. The method of claim 40, wherein the cancer is an abstract nucleophosmin (NPMl)-mutated acute myeloid leukemia (z.e., NPMlmutacute myloid leukemia).

46. The method of claim 40, wherein the cancer is a rearranged mixed lineage (KMT2A-rearranged) leukemia (MLL-r).

47. The compound of any one of claims 1-36 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 37 or claim 38, for use in treating or preventing a disease caused by, or associated with, menin expression, activity, and / or function.

48. The compound of any one of claims 1-36 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 37 or claim 38, for use in treating or preventing cancer.

49. Use of the compound of any one of claims 1-36 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 37 or claim 38, for treating or preventing a disease caused by, or associated with, menin expression, activity, and / or function.

50. Use of the compound of any one of claims 1-36 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 37 or claim 38, in the manufacture of a medicament for treating or preventing a disease caused by, or associated with, menin expression, activity, and / or function.43707-02999 / WO (S YND-070 / 001 WO)51. Use of a compound of any of claims 1-36 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 37 or claim 38, for treating or preventing cancer.

52. Use of the compound of any one of claims 1-36 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 37 or claim 38, in the manufacture of a medicament for treating or preventing cancer,53. A kit comprising the compound of any one of claims 1 -36 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 37 or claim 38 and instructions for its use.

54. A method of preparing a compound of any one of claims 1-36 or a pharmaceutically acceptable salt thereof, according to a scheme of the present disclosure or synthetic description in the Examples.

55. An intermediate useful in the preparation of a compound of any one of claims 1-36 or a pharmaceutically acceptable salt thereof.

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