Aryl ether analogs as inhibitors of the menin-mll interaction

Abstract

The present disclosure is directed to inhibitors of Formula (I), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, 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] Attorney Docket No. SYND-060 / 001WO 327830-2818 ARYL ETHER ANALOGS AS INHIBITORS OF THE MENIN-MLL INTERACTION CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to, and the benefit of, U.S. Provisional Application No. 5 63 / 579,241, filed on August 28, 2023; U.S. Provisional Application No.63 / 620,520, filed on January 12, 2024; and U.S. Provisional Application No. 63 / 651,602, filed on May 24, 2024, the entire contents of each of which are incorporated herein by reference. BACKGROUND The mixed-lineage leukemia (MLL), also known as KMT2A, gene encodes a protein 10 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 11q23 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 15 than 60 different fusion protein partners. Menin, a ubiquitously expressed, nuclear protein encoded by the multiple endocrine neoplasia type 1 (MEN1) 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. 20 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. 25 SUMMARY In one aspect, the present disclosure is directed to a compound of Formula (I),

[0002] Attorney Docket No. SYND-060 / 001WO 327830-2818 a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein: W is N or CH; Y is N or CH; 5 R1is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, 10 or N(R4a’)(R4b’); R2is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or 15 more halo, OH, oxo, CN, or N(R4a’)(R4b’); R1and R2optionally form a 3- to 12-membered heterocyclyl, wherein the heterocyclyl is optionally substituted with one or more C1-C6alkyl, halo, OH, or CN; Z is O, CH2, or NH; Ring A is 6- to 10-membered aryl or 6- to 10-membered heteroaryl, wherein the 6- to 20 10-membered aryl or 6- to 10-membered heteroaryl is optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy; X3is H, C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocyclyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b); 25 R3is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- Attorney Docket No. SYND-060 / 001WO 327830-2818 C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more R3a, or R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen 5 atom to which it is connected, wherein the 3- to 12-membered heterocyclyl 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), C1-C6alkyl, C3-C12cycloalkyl, C1-C6alkoxy, C6- C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein the C1-C610 alkyl, C3-C12cycloalkyl, C6-C10aryl, 3- to 12-membered heterocyclyl 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-C6alkyl that is optionally substituted with O(R4a), and 3- to 12- membered heterocyclyl that is optionally substituted with oxo; 15 each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6-C10aryl 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-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted 20 with C1-C6alkoxy or C(O)N(R4a’)(R4b’); each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl; and n is 1, 2, or 3. In one aspect, the present disclosure is directed to a compound of Formula (III), 25 a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein: Attorney Docket No. SYND-060 / 001WO 327830-2818 W is N or CH; Y is N or CH; R1is C1-C6alkyl or C3-C12cycloalkyl, wherein the C1-C6alkyl or the C3-C12cycloalkyl is optionally substituted with one or more halo, C1-C6alkoxy, C6-C10aryl, or 5- to 10- 5 membered heteroaryl; R2is C1-C6alkyl; Z is O, CH2, or NH; Ring A is 6- to 10-membered aryl or 6- to 10-membered heteroaryl; X3is H or C1-C6alkyl; 10 R3is H or C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more R3a, or R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen atom to which it is connected; each R3ais independently N(R4a)(R4b) or 3- to 12-membered heterocyclyl, wherein the 3- to 12-membered heterocyclyl is optionally substituted with one or more substituent 15 independently selected from C1-C6alkyl and O(R4a’); each R4aand R4bis independently C1-C6alkyl; R4a’ is H; and n is 1 or 2. In one aspect, the present application relates to a pharmaceutical composition 20 comprising a compound of the application, or a pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier. 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 a pharmaceutically acceptable carrier. 25 In one aspect, the present application relates to a pharmaceutical composition comprising a compound of the application, and a pharmaceutically acceptable carrier. In one aspect, the present application relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of the application, and a pharmaceutically acceptable carrier. 30 The present disclosure further provides a use of a compound of Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, and III, or a stereoisomer, or pharmaceutically acceptable salt thereof in a method of treating cancer in patient in need thereof. Attorney Docket No. SYND-060 / 001WO 327830-2818 The present disclosure further provides a compound of Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, and III, or a stereoisomer, or pharmaceutically acceptable salt thereof for use in a method of treating a cancer in patient in need thereof. The present disclosure further provides a compound of Formulae I, Ia, Ib, Ic, Id, Ie, If, 5 II, IIa, IIb, IIc, IId, IIe, IIf, and III, or a stereoisomer, or pharmaceutically acceptable salt thereof for use in the manufacture of a medicament for the treatment of a cancer in patient in need thereof. 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 a compound of Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, and III, or a 10 stereoisomer, or pharmaceutically acceptable salt thereof. 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 Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, and III, a stereoisomer, or a pharmaceutically acceptable salt thereof. 15 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 Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, and III, a stereoisomer, or a pharmaceutically acceptable salt thereof. The present disclosure further provides a method of treating cancer in a patient 20 comprising administering to the patient an effective amount of a compound of Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, and III, a stereoisomer, or a pharmaceutically acceptable salt thereof. 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 25 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 30 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. DETAILED DESCRIPTION In one aspect, the present disclosure is directed to a compound of Formula (I), Attorney Docket No. SYND-060 / 001WO 327830-2818 Formula (I), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein: W is N or CH; Y is N or CH; 5 R1is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, 10 or N(R4a’)(R4b’); R2is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or 15 more halo, OH, oxo, CN, or N(R4a’)(R4b’); R1and R2optionally form a 3- to 12-membered heterocyclyl, wherein the heterocyclyl is optionally substituted with one or more C1-C6alkyl, halo, OH, or CN; Z is O, CH2, or NH; Ring A is 6- to 10-membered aryl or 6- to 10-membered heteroaryl, wherein the 6- to 20 10-membered aryl or 6- to 10-membered heteroaryl is optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy; X3is H, C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocyclyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b); 25 R3is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- Attorney Docket No. SYND-060 / 001WO 327830-2818 C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more R3a, or R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen 5 atom to which it is connected, wherein the 3- to 12-membered heterocyclyl 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), C1-C6alkyl, C3-C12cycloalkyl, C1-C6alkoxy, C6- C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein the C1-C610 alkyl, C3-C12cycloalkyl, C6-C10aryl, 3- to 12-membered heterocyclyl 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-C6alkyl that is optionally substituted with O(R4a), and 3- to 12- membered heterocyclyl that is optionally substituted with oxo; 15 each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6-C10aryl 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-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted 20 with C1-C6alkoxy or C(O)N(R4a’)(R4b’); each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl; and n is 1, 2, or 3. In one aspect, the present disclosure is directed to a compound of Formula (Ia), 25 Formula (Ia), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein: Attorney Docket No. SYND-060 / 001WO 327830-2818 R1is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or 5 more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’); R2is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- 10 membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, or N(R4a’)(R4b’); R1and R2optionally form a 3- to 12-membered heterocyclyl, wherein the heterocyclyl is optionally substituted with one or more C1-C6alkyl, halo, OH, or CN; Z is O, CH2, or NH; 15 Ring A is 6- to 10-membered aryl or 6- to 10-membered heteroaryl, wherein the 6- to 10-membered aryl or 6- to 10-membered heteroaryl is optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy; X3is H, C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocyclyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or 20 N(R4a)(R4b); R3is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or 25 more R3a, or R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 12-membered heterocyclyl is optionally substituted with one or more R3a; each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b),30 OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-C6alkyl, C3-C12cycloalkyl, C1-C6alkoxy, C6- C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein the C1-C6alkyl, C3-C12cycloalkyl, C6-C10aryl, 3- to 12-membered heterocyclyl 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’), Attorney Docket No. SYND-060 / 001WO 327830-2818 N(R4a’)C(O)O(R4b’), C1-C6alkyl that is optionally substituted with O(R4a), and 3- to 12- membered heterocyclyl that is optionally substituted with oxo; each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6-C10aryl or N(R4a’)(R4b’); 5 each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted with C1-C6alkoxy or C(O)N(R4a’)(R4b’); each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- 10 membered heterocyclyl; and n is 1, 2, or 3. In one aspect, the present disclosure is directed to a compound of Formula (Ib), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein: 15 R1is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, 20 or N(R4a’)(R4b’); R2is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or 25 more halo, OH, oxo, CN, or N(R4a’)(R4b’); Attorney Docket No. SYND-060 / 001WO 327830-2818 R1and R2optionally form a 3- to 12-membered heterocyclyl, wherein the heterocyclyl is optionally substituted with one or more C1-C6alkyl, halo, OH, or CN; Z is O, CH2, or NH; Ring A is 6- to 10-membered aryl or 6- to 10-membered heteroaryl, wherein the 6- to 5 10-membered aryl or 6- to 10-membered heteroaryl is optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy; X3is H, C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocyclyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b); 10 R3is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C12 cycloalkyl, C6-C10 aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more R3a, or 15 R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 12-membered heterocyclyl 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), C1-C6alkyl, C3-C12cycloalkyl, C1-C6alkoxy, C6- 20 C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein the C1-C6alkyl, C3-C12cycloalkyl, C6-C10aryl, 3- to 12-membered heterocyclyl 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-C6alkyl that is optionally substituted with O(R4a), and 3- to 12- 25 membered heterocyclyl that is optionally substituted with oxo; each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6-C10aryl 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-C6 alkyl, C3-C12 cycloalkyl, C6-10 aryl, 5- to 10-membered 30 heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted with C1-C6alkoxy or C(O)N(R4a’)(R4b’); each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl; and n is 1, 2, or 3. Attorney Docket No. SYND-060 / 001WO 327830-2818 In one aspect, the present disclosure is directed to a compound of Formula (Ic), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein: R1is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, 5 C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’); 10 R2is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, or N(R4a’)(R4b’); 15 R1and R2optionally form a 3- to 12-membered heterocyclyl, wherein the heterocyclyl is optionally substituted with one or more C1-C6alkyl, halo, OH, or CN; Z is O, CH2, or NH; Ring A is 6- to 10-membered aryl or 6- to 10-membered heteroaryl, wherein the 6- to 10-membered aryl or 6- to 10-membered heteroaryl is optionally substituted with one or more 20 C1-C6 alkyl, halo, OH, CN, or C1-C6 alkoxy; X3is H, C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocyclyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b); R3is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl,25 C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- Attorney Docket No. SYND-060 / 001WO 327830-2818 membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more R3a, or R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 12-membered heterocyclyl is optionally 5 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), C1-C6alkyl, C3-C12cycloalkyl, C1-C6alkoxy, C6- C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein the C1-C6alkyl, C3-C12cycloalkyl, C6-C10aryl, 3- to 12-membered heterocyclyl or 5- to 10-membered 10 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’), and N(R4a’)C(O)O(R4b’), C1-C6 alkyl that is optionally substituted with O(R4a), and 3- to 12- membered heterocyclyl that is optionally substituted with oxo; each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more 15 halo, C6-C10aryl 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-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted with C1-C6alkoxy or C(O)N(R4a’)(R4b’); 20 each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl; and n is 1, 2, or 3. In one aspect, the present disclosure is directed to a compound of Formula (Id), 25 a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein: W is N or CH; Attorney Docket No. SYND-060 / 001WO 327830-2818 Y is N or CH; R1is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- 5 membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’); R2is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-10 C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, or N(R4a’)(R4b’); R1and R2optionally form a 3- to 12-membered heterocyclyl, wherein the heterocyclyl is optionally substituted with one or more C1-C6alkyl, halo, OH, or CN; 15 Ring A is 6- to 10-membered aryl or 6- to 10-membered heteroaryl, wherein the 6- to 10-membered aryl or 6- to 10-membered heteroaryl is optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy; X3is H, C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocyclyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or 20 N(R4a)(R4b); R3is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or 25 more R3a, or R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 12-membered heterocyclyl is optionally substituted with one or more R3a; each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b),30 OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-C6alkyl, C3-C12cycloalkyl, C1-C6alkoxy, C6- C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein the C1-C6alkyl, C3-C12cycloalkyl, C6-C10aryl, 3- to 12-membered heterocyclyl 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’), Attorney Docket No. SYND-060 / 001WO 327830-2818 N(R4a’)C(O)O(R4b’), C1-C6alkyl that is optionally substituted with O(R4a), and 3- to 12- membered heterocyclyl that is optionally substituted with oxo; each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6-C10aryl or N(R4a’)(R4b’); 5 each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted with C1-C6alkoxy or C(O)N(R4a’)(R4b’); each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- 10 membered heterocyclyl; and n is 1, 2, or 3. In one aspect, the present disclosure is directed to a compound of Formula (Ie), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein: 15 W is N or CH; Y is N or CH; R1is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- 20 membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’); R2is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-25 C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- Attorney Docket No. SYND-060 / 001WO 327830-2818 membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, or N(R4a’)(R4b’); R1and R2optionally form a 3- to 12-membered heterocyclyl, wherein the heterocyclyl is optionally substituted with one or more C1-C6alkyl, halo, OH, or CN; 5 Ring A is 6- to 10-membered aryl or 6- to 10-membered heteroaryl, wherein the 6- to 10-membered aryl or 6- to 10-membered heteroaryl is optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy; X3is H, C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocyclyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or 10 N(R4a)(R4b); R3is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or 15 more R3a, or R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 12-membered heterocyclyl is optionally substituted with one or more R3a; each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b),20 OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-C6alkyl, C3-C12cycloalkyl, C1-C6alkoxy, C6- C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein the C1-C6alkyl, C3-C12 cycloalkyl, C6-C10 aryl, 3- to 12-membered heterocyclyl 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’),25 N(R4a’)C(O)O(R4b’), C1-C6alkyl that is optionally substituted with O(R4a), and 3- to 12- membered heterocyclyl that is optionally substituted with oxo; each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6-C10aryl or N(R4a’)(R4b’); each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, 30 C(O)CH2-N(R4a’)(R4b’), C1-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted with C1-C6alkoxy or C(O)N(R4a’)(R4b’); each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl; and Attorney Docket No. SYND-060 / 001WO 327830-2818 n is 1, 2, or 3. In one aspect, the present disclosure is directed to a compound of Formula (If), Formula (If), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein: 5 W is N or CH; Y is N or CH; R1is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- 10 membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’); R2is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-15 C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, or N(R4a’)(R4b’); R1and R2optionally form a 3- to 12-membered heterocyclyl, wherein the heterocyclyl is optionally substituted with one or more C1-C6alkyl, halo, OH, or CN; 20 Ring A is 6- to 10-membered aryl or 6- to 10-membered heteroaryl, wherein the 6- to 10-membered aryl or 6- to 10-membered heteroaryl is optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy; X3is H, C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocyclyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or 25 N(R4a)(R4b); Attorney Docket No. SYND-060 / 001WO 327830-2818 R3is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or 5 more R3a, or R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 12-membered heterocyclyl is optionally substituted with one or more R3a; each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b),10 OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-C6alkyl, C3-C12cycloalkyl, C1-C6alkoxy, C6- C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein the C1-C6alkyl, C3-C12 cycloalkyl, C6-C10 aryl, 3- to 12-membered heterocyclyl 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’),15 N(R4a’)C(O)O(R4b’), C1-C6alkyl that is optionally substituted with O(R4a), and 3- to 12- membered heterocyclyl that is optionally substituted with oxo; each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6-C10aryl or N(R4a’)(R4b’); each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, 20 C(O)CH2-N(R4a’)(R4b’), C1-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted with C1-C6 alkoxy or C(O)N(R4a’)(R4b’); each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl; and 25 n is 1, 2, or 3. In one aspect, the present disclosure is directed to a compound of Formula (II),

[0003] Attorney Docket No. SYND-060 / 001WO 327830-2818 a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein: W is N or CH; Y is N or CH; 5 R1is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, 10 or N(R4a’)(R4b’); Z is O, CH2, or NH; Ring A is 6- to 10-membered aryl or 6- to 10-membered heteroaryl, wherein the 6- to 10-membered aryl or 6- to 10-membered heteroaryl is optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy; 15 X3is H, C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocyclyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b); R3is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-20 C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more R3a, or R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 12-membered heterocyclyl is optionally 25 substituted with one or more R3a; Attorney Docket No. SYND-060 / 001WO 327830-2818 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-C6alkyl, C3-C12cycloalkyl, C1-C6alkoxy, C6- C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein the C1-C6alkyl, C3-C12cycloalkyl, C6-C10aryl, 3- to 12-membered heterocyclyl or 5- to 10-membered 5 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-C6alkyl that is optionally substituted with O(R4a), and 3- to 12- membered heterocyclyl that is optionally substituted with oxo; each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more 10 halo, C6-C10aryl 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-C6 alkyl, C3-C12 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted with C1-C6alkoxy or C(O)N(R4a’)(R4b’); 15 each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl; and n is 1, 2, or 3. In one aspect, the present disclosure is directed to a compound of Formula (IIa), Formula (IIb), or Formula (IIc),

[0004] Attorney Docket No. SYND-060 / 001WO 327830-2818 a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein: W is N or CH; 5 Y is N or CH; R1is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or 10 more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’); X3is H, C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocyclyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b); 15 R3is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- Attorney Docket No. SYND-060 / 001WO 327830-2818 membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more R3a, or R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 12-membered heterocyclyl is optionally 5 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), C1-C6alkyl, C3-C12cycloalkyl, C1-C6alkoxy, C6- C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein the C1-C6alkyl, C3-C12cycloalkyl, C6-C10aryl, 3- to 12-membered heterocyclyl or 5- to 10-membered 10 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-C6 alkyl that is optionally substituted with O(R4a), and 3- to 12- membered heterocyclyl that is optionally substituted with oxo; each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more 15 halo, C6-C10aryl 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-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted with C1-C6alkoxy or C(O)N(R4a’)(R4b’); and 20 each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl. In one aspect, the present disclosure is directed to a compound of Formula (IId), Formula (IIe), or Formula (IIf),

[0005] Attorney Docket No. SYND-060 / 001WO 327830-2818 a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein: W is N or CH; 5 Y is N or CH; R1is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or 10 more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’); Z is O, CH2, or NH; X3is H, C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocyclyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or 15 N(R4a)(R4b); R3is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- Attorney Docket No. SYND-060 / 001WO 327830-2818 C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more R3a, or R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen 5 atom to which it is connected, wherein the 3- to 12-membered heterocyclyl 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), C1-C6alkyl, C3-C12cycloalkyl, C1-C6alkoxy, C6- C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein the C1-C610 alkyl, C3-C12cycloalkyl, C6-C10aryl, 3- to 12-membered heterocyclyl 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-C6alkyl that is optionally substituted with O(R4a), and 3- to 12- membered heterocyclyl that is optionally substituted with oxo; 15 each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6-C10aryl 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-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted 20 with C1-C6alkoxy or C(O)N(R4a’)(R4b’); and each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl. In one aspect, the present disclosure is directed to a compound of Formula (III), 25 a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein: W is N or CH; Attorney Docket No. SYND-060 / 001WO 327830-2818 Y is N or CH; R1is C1-C6alkyl or C3-C12cycloalkyl, wherein the C1-C6alkyl or the C3-C12cycloalkyl is optionally substituted with one or more halo, C1-C6alkoxy, C6-C10aryl, or 5- to 10- membered heteroaryl; 5 R2is C1-C6alkyl; Z is O, CH2, or NH; Ring A is 6- to 10-membered aryl or 6- to 10-membered heteroaryl; X3is H or C1-C6alkyl; R3is H or C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or 10 more R3a; or R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen atom to which it is connected; each R3ais independently N(R4a)(R4b) or 3- to 12-membered heterocyclyl, wherein the 3- to 12-membered heterocyclyl is optionally substituted with one or more substituent 15 independently selected from C1-C6alkyl and O(R4a’); each R4aand R4bis independently C1-C6alkyl; R4a’ is H; and n is 1 or 2. 20 Embodiments For any of Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, and III where applicable, the following embodiments are considered both alone and in conjunction with another where a stable compound is formed. In some embodiments, W is N or CH. 25 In some embodiments, W is N. In some embodiments, W is CH. In some embodiments, Y is N or CH. In some embodiments, Y is N. In some embodiments, Y is CH. 30 In some embodiments, R1is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10 Attorney Docket No. SYND-060 / 001WO 327830-2818 aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R1is H. In some embodiments, R1is C1-C6alkyl. 5 In some embodiments, R1is C1-C5alkyl. In some embodiments, R1is C1-C4alkyl. In some embodiments, R1is C1-C3alkyl. In some embodiments, R1is C1-C2alkyl. In some embodiments, R1is methyl. 10 In some embodiments, R1is ethyl. In some embodiments, R1is propyl. In some embodiments, R1is isopropyl. In some embodiments, R1is butyl. In some embodiments, R1is tert-butyl. 15 In some embodiments, R1is C1-C6alkyl substituted by one or more halo , OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl. In some embodiments, R1is C1-C5alkyl substituted by one or more halo, OH, oxo, CN, 20 C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl. In some embodiments, R1is C1-C4alkyl substituted by one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’),25 wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl. In some embodiments, R1is C1-C3alkyl substituted by one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6 alkyl, C3-C12 cycloalkyl, or 3- to 12- 30 membered heterocyclyl. In some embodiments, R1is C1-C2alkyl substituted by one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R1is C1-C6alkyl substituted by one or more fluorine atoms. In some embodiments, R1is C1-C5alkyl substituted by one or more fluorine atoms. In some embodiments, R1is C1-C4alkyl substituted by one or more fluorine atoms. In some embodiments, R1is C1-C3alkyl substituted by one or more fluorine atoms. 5 In some embodiments, R1is C1-C2alkyl substituted by one or more fluorine atoms. In some embodiments, R1is -CH2-CF3, -CH2-CHF2, or -CH2-CH2F. In some embodiments, R1is C1-C6alkyl substituted by one or more CN. In some embodiments, R1is C1-C5alkyl substituted by one or more CN. In some embodiments, R1is C1-C4alkyl substituted by one or more CN. 10 In some embodiments, R1is C1-C3alkyl substituted by one or more CN. In some embodiments, R1is C1-C2alkyl substituted by one or more CN. In some embodiments, R1is -CH2-CN. In some embodiments, R1is C1-C6alkyl substituted by one or more C6-C10aryl. In some embodiments, R1is C1-C5alkyl substituted by one or more C6-C10aryl. 15 In some embodiments, R1is C1-C4alkyl substituted by one or more C6-C10aryl. In some embodiments, R1is C1-C3alkyl substituted by one or more C6-C10aryl. In some embodiments, R1is C1-C2alkyl substituted by one or more C6-C10aryl. In some embodiments, R1is -CH2-phenyl. In some embodiments, R1is C2-C6alkenyl. 20 In some embodiments, R1is C2-C5alkenyl. In some embodiments, R1is C2-C4alkenyl. In some embodiments, R1is C2-C3 alkenyl. In some embodiments, R1is C2-C6alkenyl substituted by one or more halo, OH, oxo, CN, C1-C6alkyl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, 25 C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R1is C2-C5alkenyl substituted by one or more halo, OH, oxo, CN, C1-C6alkyl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R1is C2-C4 alkenyl substituted by one or more halo, OH, oxo, 30 CN, C1-C6alkyl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R1is C2-C3alkenyl substituted by one or more halo, OH, oxo, CN, C1-C6alkyl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R1is C2-C6alkenyl substituted by one or more fluorine atoms. In some embodiments, R1is C2-C5alkenyl substituted by one or more fluorine atoms. In some embodiments, R1is C2-C4alkenyl substituted by one or more fluorine atoms. In some embodiments, R1is C2-C3alkenyl substituted by one or more fluorine atoms. 5 In some embodiments, R1is -CH=CF2, or -CH=CHF. In some embodiments, R1is 3- to 12-membered heterocyclyl. In some embodiments, R1is 3- to 11-membered heterocyclyl. In some embodiments, R1is 3- to 10-membered heterocyclyl. In some embodiments, R1is 3- to 9-membered heterocyclyl. 10 In some embodiments, R1is 3- to 8-membered heterocyclyl. In some embodiments, R1is 3- to 7-membered heterocyclyl. In some embodiments, R1is 3- to 6-membered heterocyclyl. In some embodiments, R1is 3- to 5-membered heterocyclyl. In some embodiments, R1is 3- to 4-membered heterocyclyl. 15 In some embodiments, R1is 3- to 12-membered heterocyclyl substituted by one or more halo. In some embodiments, R1is 3- to 11-membered heterocyclyl substituted by one or more halo, OH, oxo, CN, C1-C6alkyl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. 20 In some embodiments, R1is 3- to 10-membered heterocyclyl substituted by one or more halo, OH, oxo, CN, C1-C6alkyl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6 alkyl, C3-C12 cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R1is 3- to 9-membered heterocyclyl substituted by one or more halo, OH, oxo, CN, C1-C6alkyl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently 25 H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R1is 3- to 8-membered heterocyclyl substituted by one or more halo, OH, oxo, CN, C1-C6alkyl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R1is 3- to 7-membered heterocyclyl substituted by one or more 30 halo, OH, oxo, CN, C1-C6alkyl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R1is 3- to 6-membered heterocyclyl substituted by one or more halo, OH, oxo, CN, C1-C6alkyl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R1is 3- to 5-membered heterocyclyl substituted by one or more halo, OH, oxo, CN, C1-C6alkyl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R1is 3- to 4-membered heterocyclyl substituted by one or more 5 halo, OH, oxo, CN, C1-C6alkyl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R1is 3- to 12-membered heterocyclyl substituted by one or more fluorine atoms. In some embodiments, R1is 3- to 11-membered heterocyclyl substituted by one or more 10 fluorine atoms. In some embodiments, R1is 3- to 10-membered heterocyclyl substituted by one or more fluorine atoms. In some embodiments, R1is 3- to 9-membered heterocyclyl substituted by one or more fluorine atoms. 15 In some embodiments, R1is 3- to 8-membered heterocyclyl substituted by one or more fluorine atoms. In some embodiments, R1is 3- to 7-membered heterocyclyl substituted by one or more fluorine atoms. In some embodiments, R1is 3- to 6-membered heterocyclyl substituted by one or more 20 fluorine atoms. In some embodiments, R1is 3- to 5-membered heterocyclyl substituted by one or more fluorine atoms. In some embodiments, R1is 3- to 4-membered heterocyclyl substituted by one or more fluorine atoms. 25 In some embodiments, R1is C3-C12cycloalkyl. In some embodiments, R1is C3-C11cycloalkyl. In some embodiments, R1is C3-C10cycloalkyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R1is C3-C9cycloalkyl. In some embodiments, R1is C3-C8cycloalkyl. In some embodiments, R1is C3-C7cycloalkyl. In some embodiments, R1is C3-C6cycloalkyl. 5 In some embodiments, R1is C3-C5cycloalkyl. In some embodiments, R1is C3-C4cycloalkyl. In some embodiments, R1is cyclopropyl. In some embodiments, R1is cyclobutyl. In some embodiments, R1is cyclopentyl. 10 In some embodiments, R1is cyclohexyl. In some embodiments, R1is cycloheptyl. In some embodiments, R1is cyclooctyl. In some embodiments, R1is cyclopentenyl. In some embodiments, R1is cyclohexenyl. 15 In some embodiments, R1is cycloheptenyl. In some embodiments, R1is C3-C12cycloalkyl substituted by one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. 20 In some embodiments, R1is C3-C11cycloalkyl substituted by one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6 alkyl, C3-C12 cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R1is C3-C10cycloalkyl substituted by one or more halo, OH, 25 oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R1is C3-C9cycloalkyl substituted by one or more halo, OH, oxo, CN, C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, 5- to 10-membered heteroaryl, or 30 N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R1is C3-C8cycloalkyl substituted by one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or Attorney Docket No. SYND-060 / 001WO 327830-2818 N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R1is C3-C7cycloalkyl substituted by one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or 5 N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R1is C3-C6cycloalkyl substituted by one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, 10 or 3- to 12-membered heterocyclyl. In some embodiments, R1is C3-C5cycloalkyl substituted by one or more halo, OH, oxo, CN, C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. 15 In some embodiments, R1is C3-C4cycloalkyl substituted by one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R1is cyclopropyl substituted by one or more fluorine atoms. 20 In some embodiments, R1is cyclobutyl substituted by one or more fluorine atoms. In some embodiments, R1is cyclobutyl substituted by two methyl groups. In some embodiments, R1is cyclobutyl substituted by one fluorine atom and one methyl group. In some embodiments, R1is cyclobutyl substituted by two fluorine atoms and one 25 methyl group. In some embodiments, R1is cyclobutyl substituted by one OH and one methyl group. In some embodiments, R1is cyclobutyl substituted by one CN and one methyl group. In some embodiments, R1is cyclobutyl substituted by one methoxy group. In some embodiments, R1is cyclobutyl substituted by one 5- to 10-membered 30 heteroaryl. In some embodiments, R1is cyclobutyl substituted by one 1H-pyrazol-1-yl group. In some embodiments, R1is cyclobutyl substituted by one 1H-imidazol-1-yl group. In some embodiments, R1is cyclobutyl substituted by one 5- to 10-membered heteroaryl and one methyl group. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R1is cyclobutyl substituted by one 1H-pyrazol-1-yl group and one methyl group. In some embodiments, R1is cyclobutyl substituted by one 1H-imidazol-1-yl group and one methyl group. 5 In some embodiments, R1is cyclopentyl substituted by one or more fluorine atoms. In some embodiments, R1is cyclohexyl substituted by one or more fluorine atoms. In some embodiments, R1is cycloheptyl substituted by one or more fluorine atoms. In some embodiments, R1is cyclooctyl substituted by one or more fluorine atoms. In some embodiments, R1is cyclopentenyl substituted by one or more fluorine atoms. 10 In some embodiments, R1is cyclohexenyl substituted by one or more fluorine atoms. In some embodiments, R1is cycloheptenyl substituted by one or more fluorine atoms. In some embodiments, In some embodiments, R2is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered 15 heterocyclyl, wherein the C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. 20 In some embodiments, R1is 5- to 10-membered heteroaryl optionally substituted with one or more C1-C6alkyl. In some embodiments, R1is 5- to 9-membered heteroaryl optionally substituted with one or more C1-C6alkyl. In some embodiments, R1is 5- to 8-membered heteroaryl optionally substituted with 25 one or more C1-C6alkyl. In some embodiments, R1is 5- to 7-membered heteroaryl optionally substituted with one or more C1-C6alkyl. In some embodiments, R1is 5- to 6-membered heteroaryl optionally substituted with one or more C1-C6alkyl. 30 In some embodiments, R1is 5-membered heteroaryl optionally substituted with one or more C1-C6alkyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R1is 6-membered heteroaryl optionally substituted with one or more C1-C6alkyl. In some embodiments, R1is 7-membered heteroaryl optionally substituted with one or more C1-C6alkyl. 5 In some embodiments, R1is 8-membered heteroaryl optionally substituted with one or more C1-C6alkyl. In some embodiments, R1is 9-membered heteroaryl optionally substituted with one or more C1-C6alkyl. In some embodiments, R1is 10-membered heteroaryl optionally substituted with one 10 or more C1-C6alkyl. In some embodiments, R1is 5-membered heteroaryl optionally substituted with one or more methyl. In some embodiments, R1is 6-membered heteroaryl optionally substituted with one or more methyl. 15 In some embodiments, R1is 7-membered heteroaryl optionally substituted with one or more methyl. In some embodiments, R1is 8-membered heteroaryl optionally substituted with one or more methyl. In some embodiments, R1is 9-membered heteroaryl optionally substituted with one or 20 more methyl. In some embodiments, R1is 10-membered heteroaryl optionally substituted with one or more methyl. In some embodiments, In some embodiments, R2is H. 25 In some embodiments, R2is C1-C6alkyl. In some embodiments, R2is C1-C5alkyl. In some embodiments, R2is C1-C4alkyl. In some embodiments, R2is C1-C3alkyl. In some embodiments, R2is C1-C2alkyl. 30 In some embodiments, R2is methyl. In some embodiments, R2is ethyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R2is propyl. In some embodiments, R2is isopropyl. In some embodiments, R2is butyl. In some embodiments, R2is tert-butyl. 5 In some embodiments, R1and R2optionally form a 3- to 12-membered heterocyclyl. In some embodiments, R1and R2optionally form a 3- to 12-membered heterocyclyl, wherein the heterocyclyl is optionally substituted with one or more C1-C6alkyl, halo, OH, or CN. In some embodiments, R1and R2form a 3- to 12-membered heterocyclyl. 10 In some embodiments, R1and R2form a 3- to 11-membered heterocyclyl. In some embodiments, R1and R2form a 3- to 10-membered heterocyclyl. In some embodiments, R1and R2form a 3- to 9-membered heterocyclyl. In some embodiments, R1and R2form a 3- to 8-membered heterocyclyl. In some embodiments, R1and R2form a 3- to 7-membered heterocyclyl. 15 In some embodiments, R1and R2form a 3- to 6-membered heterocyclyl. In some embodiments, R1and R2form a 3- to 5-membered heterocyclyl. In some embodiments, R1and R2form a 3- to 4-membered heterocyclyl. In some embodiments, R1and R2form a 3- to 12-membered heterocyclyl substituted by one or more C1-C6alkyl, halo, OH, or CN. 20 In some embodiments, R1and R2form a 3- to 11-membered heterocyclyl substituted by one or more C1-C6alkyl, halo, OH, or CN. In some embodiments, R1and R2form a 3- to 10-membered heterocyclyl substituted by one or more C1-C6alkyl, halo, OH, or CN. In some embodiments, R1and R2form a 3- to 9-membered heterocyclyl substituted by 25 one or more C1-C6alkyl, halo, OH, or CN. In some embodiments, R1and R2form a 3- to 8-membered heterocyclyl substituted by one or more C1-C6alkyl, halo, OH, or CN. In some embodiments, R1and R2form a 3- to 7-membered heterocyclyl substituted by one or more C1-C6 alkyl, halo, OH, or CN. 30 In some embodiments, R1and R2form a 3- to 6-membered heterocyclyl substituted by one or more C1-C6alkyl, halo, OH, or CN. In some embodiments, R1and R2form a 3- to 5-membered heterocyclyl substituted by one or more C1-C6alkyl, halo, OH, or CN. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R1and R2form a 3- to 4-membered heterocyclyl substituted by one or more C1-C6alkyl, halo, OH, or CN. In some embodiments, R1and R2form a morpholinyl group. In some embodiments, R1and R2form a morpholinyl group substituted by one or more 5 C1-C6alkyl, halo, OH, or CN. In some embodiments, R1and R2form a morpholinyl group substituted by one or more methyl, halo, OH, or CN. In some embodiments, R1and R2form a group selected from: . 10 In some embodiments, Z is O, CH2, or NH . In some embodiments, Z is O. In some embodiments, Z is CH2. In some embodiments, Z is NH. In some embodiments, Ring A is 6- to 10-membered aryl or 6- to 10-membered 15 heteroaryl, wherein the 6- to 10-membered aryl or 6- to 10-membered heteroaryl is optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy. In some embodiments, Ring A is 6- to 10-membered aryl optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy. In some embodiments, Ring A is 6- to 9-membered aryl optionally substituted with one 20 or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy. In some embodiments, Ring A is 6- to 8-membered aryl optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy. In some embodiments, Ring A is 6- to 7-membered aryl optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy. 25 In some embodiments, Ring A is a phenyl ring. In some embodiments, Ring A is 6- to 10-membered heteroaryl optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy. In some embodiments, Ring A is 6- to 9-membered heteroaryl optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy. 30 In some embodiments, Ring A is 6- to 8-membered heteroaryl optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, Ring A is 6- to7-membered heteroaryl optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy. In some embodiments, Ring A is a pyridine ring. In some embodiments, Ring A is a pyridine ring substituted with one halo. 5 In some embodiments, Ring A is a pyridine ring substituted with one fluorine atom. In some embodiments, Ring A is a pyrimidine ring. In some embodiments, Ring A is a pyridine ring optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy. In some embodiments, Ring A is a pyrimidine ring optionally substituted with one or 10 more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy. In some embodiments, Ring A is a pyridine ring optionally substituted with one or more fluorine atoms. In some embodiments, Ring A is a pyrimidine ring optionally substituted with one or more fluorine atoms. 15 In some embodiments, Ring wherein represents a bond to Z. In some embodiments, X3is H, C1-C6alkyl, wherein the C1-C6alkyl is optionally 20 substituted with one or more halo, 3- to 12-membered heterocyclyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b); wherein: Attorney Docket No. SYND-060 / 001WO 327830-2818 each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6-C10aryl 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-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered 5 heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted with C1-C6alkoxy or C(O)N(R4a’)(R4b’); and each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl. In some embodiments, X3is H. 10 In some embodiments, X3is C1-C6alkyl. In some embodiments, X3is C1-C5alkyl. In some embodiments, X3is C1-C4 alkyl. In some embodiments, X3is C1-C3alkyl. In some embodiments, X3is C1-C2alkyl. 15 In some embodiments, X3is methyl. In some embodiments, X3is ethyl. In some embodiments, X3is propyl. In some embodiments, X3is isopropyl. In some embodiments, X3is butyl. 20 In some embodiments, X3is tert-butyl. In some embodiments, X3is C1-C6alkyl substituted by one or more -OH. In some embodiments, X3is C1-C5 alkyl substituted by one or more -OH. In some embodiments, X3is C1-C4alkyl substituted by one or more -OH. In some embodiments, X3is C1-C3alkyl substituted by one or more -OH. 25 In some embodiments, X3is C1-C2alkyl substituted by one or more -OH. In some embodiments, X3is C1-C6alkyl substituted by one or more -OH. In some embodiments, X3is C1-C5alkyl substituted by one or more -OH. In some embodiments, X3is C1-C4alkyl substituted by one or more -OH. In some embodiments, X3is C1-C3 alkyl substituted by one or more -OH. 30 In some embodiments, X3is C1-C2alkyl substituted by one or more -OH. In some embodiments, X3is -CH2(OH), -CH2-CH2(OH), or -CH2-CH2-CH2(OH). In some embodiments, X3is C1-C6alkyl substituted by one or more OR4a; wherein each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6- Attorney Docket No. SYND-060 / 001WO 327830-2818 C10aryl or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, X3is C1-C5alkyl substituted by one or more OR4a; wherein each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6- 5 C10aryl or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, X3is C1-C4alkyl substituted by one or more OR4a; wherein each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6- C10aryl or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C1210 cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, X3is C1-C3alkyl substituted by one or more OR4a; wherein each R4ais independently H, CN, or C1-C6 alkyl optionally substituted with one or more halo, C6- C10aryl or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. 15 In some embodiments, X3is C1-C2alkyl substituted by one or more OR4a; wherein each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6- C10aryl or N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, X3is -CH2-OCH3, -CH2-CH2-OCH3, -CH2-CH2-CH2-OCH3, - 20 CH2-O-CH2-CHF2, -CH2-CH2-CH2-O-CHF2, or -CH2-O-CH2-CH2-N(CH3)2. In some embodiments, X3is -CH2-O-CH2-phenyl, -CH2-CH2-O-CH2-phenyl, or -CH2- CH2-CH2-O-CH2-phenyl. In some embodiments, X3is C1-C6alkyl substituted by one or more C(=O)N(R4a)(R4b); wherein: 25 each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6-C10aryl 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-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6 alkyl is optionally substituted 30 with C1-C6alkoxy or C(O)N(R4a’)(R4b’); and each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl. In some embodiments, X3is C1-C6alkyl substituted by one or more C(=O)N(CH3)2. In some embodiments, X3is C1-C5alkyl substituted by one or more C(=O)N(CH3)2. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, X3is C1-C4alkyl substituted by one or more C(=O)N(CH3)2. In some embodiments, X3is C1-C3alkyl substituted by one or more C(=O)N(CH3)2. In some embodiments, X3is C1-C2alkyl substituted by one or more C(=O)N(CH3)2. In some embodiments, X3is -CH2-C(=O)N(CH3)2, -CH2-CH2-C(=O)N(CH3)2,or -CH2- 5 CH2-CH2-C(=O)N(CH3)2. In some embodiments, X3is C1-C6alkyl substituted by one or more N(R4a)(R4b); wherein: each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6-C10aryl or N(R4a’)(R4b’), 10 each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6 alkyl is optionally substituted with C1-C6alkoxy or C(O)N(R4a’)(R4b’); and each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- 15 membered heterocyclyl. In some embodiments, X3is C1-C6alkyl substituted by one or more -N(CH3)2. In some embodiments, X3is C1-C5alkyl substituted by one or more -N(CH3)2. In some embodiments, X3is C1-C4alkyl substituted by one or more -N(CH3)2. In some embodiments, X3is C1-C3alkyl substituted by one or more -N(CH3)2. 20 In some embodiments, X3is C1-C2alkyl substituted by one or more -N(CH3)2. In some embodiments, X3is -CH2-N(CH3)2, -CH2-CH2-N(CH3)2,or -CH2-CH2-CH2- N(CH3)2. In some embodiments, X3is C1-C6alkyl substituted with S(=O)2R4a, wherein R4ais C1- C6alkyl. 25 In some embodiments, X3is C1-C5alkyl substituted with S(=O)2R4a, wherein R4ais C1- C6alkyl. In some embodiments, X3is C1-C4alkyl substituted with S(=O)2R4a, wherein R4ais C1- C6alkyl. In some embodiments, X3is C1-C3 alkyl substituted with S(=O)2R4a, wherein R4ais C1- 30 C6alkyl. In some embodiments, X3is C1-C2alkyl substituted with S(=O)2R4a, wherein R4ais C1- C6alkyl. In some embodiments, X3is -CH2-CH2-S(O)2-CH3or -CH2-CH2-CH2-S(O)2-CH3. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, X3is C1-C6alkyl substituted with N(R4a)(R4b), wherein R4ais H and R4bis C(O)R4b’, and wherein R4b’ is C1-C6alkyl. In some embodiments, X3is C1-C5alkyl substituted with N(R4a)(R4b), wherein R4ais H and R4bis C(O)R4b’, and wherein R4b’ is C1-C6alkyl. 5 In some embodiments, X3is C1-C4alkyl substituted with N(R4a)(R4b), wherein R4ais H and R4bis C(O)R4b’, and wherein R4b’ is C1-C6alkyl. In some embodiments, X3is C1-C3alkyl substituted with N(R4a)(R4b), wherein R4ais H and R4bis C(O)R4b’, and wherein R4b’ is C1-C6alkyl. In some embodiments, X3is C1-C2 alkyl substituted with N(R4a)(R4b), wherein R4ais H 10 and R4bis C(O)R4b’, and wherein R4b’ is C1-C6alkyl. In some embodiments, X3is -CH2-CH2-NH-C(O)-CH3. In some embodiments, X3is C1-C6alkyl substituted with N(R4a)(R4b), wherein R4ais H and R4bis S(=O)2R4b’, and wherein R4b’ is C1-C6alkyl. In some embodiments, X3is C1-C5alkyl substituted with N(R4a)(R4b), wherein R4ais H 15 and R4bis S(=O)2R4b’, and wherein R4b’ is C1-C6alkyl. In some embodiments, X3is C1-C4 alkyl substituted with N(R4a)(R4b), wherein R4ais H and R4bis S(=O)2R4b’, and wherein R4b’ is C1-C6alkyl. In some embodiments, X3is C1-C3alkyl substituted with N(R4a)(R4b), wherein R4ais H and R4bis S(=O)2R4b’, and wherein R4b’ is C1-C6alkyl. 20 In some embodiments, X3is C1-C2alkyl substituted with N(R4a)(R4b), wherein R4ais H and R4bis S(=O)2R4b’, and wherein R4b’ is C1-C6alkyl. In some embodiments, X3is -CH2-CH2-NH-S(O)2-CH3. In some embodiments, X3is C1-C6alkyl substituted with 3- to 12-membered heterocyclyl. 25 In some embodiments, X3is C1-C5alkyl substituted with 3- to 12-membered heterocyclyl. In some embodiments, X3is C1-C4alkyl substituted with 3- to 12-membered heterocyclyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, X3is C1-C3alkyl substituted with 3- to 12-membered heterocyclyl. In some embodiments, X3is C1-C2alkyl substituted with 3- to 12-membered heterocyclyl. 5 In some embodiments, In some embodiments, R3is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C12 cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl is 10 optionally substituted with one or more R3a; wherein: 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-C6alkyl, C3-C12cycloalkyl, C1-C6alkoxy, C6- C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein the C1-C6alkyl, C3-C12cycloalkyl, C6-C10aryl, 3- to 12-membered heterocyclyl or 5- to 10-membered 15 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-C6alkyl that is optionally substituted with O(R4a), and 3- to 12- membered heterocyclyl that is optionally substituted with oxo; each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more 20 halo, C6-C10aryl 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-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted with C1-C6alkoxy or C(O)N(R4a’)(R4b’); 25 each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl. In some embodiments, R3is H. In some embodiments, R3is C1-C6alkyl. In some embodiments, R3is C1-C5alkyl. 30 In some embodiments, R3is C1-C4alkyl. In some embodiments, R3is C1-C3alkyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is C1-C2alkyl. In some embodiments, R3is methyl. In some embodiments, R3is -CD3. In some embodiments, R3is ethyl. In some embodiments, R3is propyl. 5 In some embodiments, R3is isopropyl. In some embodiments, R3is butyl. In some embodiments, R3is C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted by one or more R3aand wherein R3ais a halo. In some embodiments, R3is C1-C5alkyl, wherein the C1-C5alkyl is optionally 10 substituted by one or more R3aand wherein R3ais a halo. In some embodiments, R3is C1-C4alkyl, wherein the C1-C4alkyl is optionally substituted by one or more R3aand wherein R3ais a halo. In some embodiments, R3is C1-C3alkyl, wherein the C1-C3alkyl is optionally substituted by one or more R3aand wherein R3ais a halo. 15 In some embodiments, R3is C1-C2alkyl, wherein the C1-C2alkyl is optionally substituted by one or more R3aand wherein R3ais a halo. In some embodiments, R3is C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted by one or more R3aand wherein R3ais a fluoro. In some embodiments, R3is C1-C5alkyl, wherein the C1-C5alkyl is optionally 20 substituted by one or more R3aand wherein R3ais a fluoro. In some embodiments, R3is C1-C4alkyl, wherein the C1-C4alkyl is optionally substituted by one or more R3aand wherein R3ais a fluoro. In some embodiments, R3is C1-C3alkyl, wherein the C1-C3alkyl is optionally substituted by one or more R3aand wherein R3ais a fluoro. 25 In some embodiments, R3is C1-C2alkyl, wherein the C1-C2alkyl is optionally substituted by one or more R3aand wherein R3ais a fluoro. In some embodiments, R3is methyl, wherein the methyl is optionally substituted by one or more R3aand wherein R3ais a halo. In some embodiments, R3is ethyl, wherein the ethyl is optionally substituted by one or more R3aand wherein R3ais a halo. In some embodiments, 30 R3is ethyl, wherein the ethyl is optionally substituted by one or more R3aand wherein R3ais a fluoro. In some embodiments, R3is . Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is propyl, wherein the propyl is optionally substituted by one or more R3aand wherein R3ais a halo. In some embodiments, R3is isopropyl, wherein the isopropyl is optionally substituted by one or more R3aand wherein R3ais a halo. 5 In some embodiments, R3is butyl, wherein the butyl is optionally substituted by one or more R3aand wherein R3ais a halo. In some embodiments, R3is tert-butyl, wherein the tert-butyl is optionally substituted by one or more R3aand wherein R3ais a halo. In some embodiments, R3is 2-methyl propyl, wherein the 2-methyl propyl is optionally 10 substituted by one or more R3aand wherein R3ais a halo. In one embodiment, R3is 2-methyl propyl, wherein the 2-methyl propyl is optionally substituted by one or more R3aand wherein R3ais a fluoro. In some embodiments, R3is . In some embodiments, R3is a C3-C12cycloalkyl. In some embodiments, R3is a C3-C11cycloalkyl. 15 In some embodiments, R3is a C3-C10cycloalkyl. In some embodiments, R3is a C3-C9cycloalkyl. In some embodiments, R3is a C3-C8cycloalkyl. In some embodiments, R3is a C3-C7cycloalkyl. In some embodiments, R3is a C3-C6cycloalkyl. 20 In some embodiments, R3is a C3-C5 cycloalkyl. In some embodiments, R3is a C3-C4cycloalkyl. In some embodiments, In some embodiments, R3is a C3-C12cycloalkyl wherein the cycloalkyl is optionally substituted by one or more R3a, and wherein: 25 each R3ais independently halo, OR4a, oxo, CN, N(R4a)(R4b), or C1-C6alkyl, and each R4aand R4bis H. In some embodiments, R3is a C3-C12cycloalkyl wherein the C3-C12cycloalkyl is optionally substituted by one or more halo, OH, oxo, CN, NH2, or C1-C6alkyl. In some embodiments, R3is a C3-C11cycloalkyl wherein the C3-C11cycloalkyl is 30 optionally substituted by one or more halo, OH, oxo, CN, NH2, or C1-C6alkyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is a C3-C10cycloalkyl wherein the C3-C10cycloalkyl is optionally substituted by one or more halo, OH, oxo, CN, NH2, or C1-C6alkyl. In some embodiments, R3is a C3-C9cycloalkyl wherein the C3-C9cycloalkyl is optionally substituted by one or more halo, OH, oxo, CN, NH2, or C1-C6alkyl. 5 In some embodiments, R3is a C3-C8cycloalkyl wherein the C3-C8cycloalkyl is optionally substituted by one or more halo, OH, oxo, CN, NH2, or C1-C6alkyl. In some embodiments, R3is a C3-C7cycloalkyl wherein the C3-C7cycloalkyl is optionally substituted by one or more halo, OH, oxo, CN, NH2, or C1-C6alkyl. In some embodiments, R3is a C3-C6cycloalkyl wherein the C3-C6cycloalkyl is 10 optionally substituted by one or more halo, OH, oxo, CN, NH2, or C1-C6alkyl. In some embodiments, R3is a C3-C5cycloalkyl wherein the C3-C5cycloalkyl is optionally substituted by one or more halo, OH, oxo, CN, NH2, or C1-C6 alkyl. In some embodiments, R3is a C3-C4cycloalkyl wherein the C3-C4cycloalkyl is optionally substituted by one or more halo, OH, oxo, CN, NH2, or C1-C6alkyl. 15 In some embodiments, R3is . In some embodiments, R3is a C3-C12cycloalkyl wherein the cycloalkyl is optionally substituted by one or more R3a, and wherein: each R3ais independently halo, OR4a, oxo, CN, N(R4a)(R4b), or C1-C6alkyl, and each R4aand R4bis CH3. 20 In some embodiments, R3is a C3-C12cycloalkyl wherein the C3-C12cycloalkyl is optionally substituted by one or more halo, OCH3, oxo, CN, N(CH3)2, or C1-C6alkyl. In some embodiments, R3is a C3-C11cycloalkyl wherein the C3-C11cycloalkyl is optionally substituted by one or more halo, OCH3, oxo, CN, N(CH3)2, or C1-C6alkyl. In some embodiments, R3is a C3-C10cycloalkyl wherein the C3-C10cycloalkyl is 25 optionally substituted by one or more halo, OCH3, oxo, CN, N(CH3)2, or C1-C6alkyl. In some embodiments, R3is a C3-C9cycloalkyl wherein the C3-C9cycloalkyl is optionally substituted by one or more halo, OCH3, oxo, CN, N(CH3)2, or C1-C6alkyl. In some embodiments, R3is a C3-C8cycloalkyl wherein the C3-C8cycloalkyl is optionally substituted by one or more halo, OCH3, oxo, CN, N(CH3)2, or C1-C6alkyl. 30 In some embodiments, R3is a C3-C7cycloalkyl wherein the C3-C7cycloalkyl is optionally substituted by one or more halo, OCH3, oxo, CN, N(CH3)2, or C1-C6alkyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is a C3-C6cycloalkyl wherein the C3-C6cycloalkyl is optionally substituted by one or more halo, OCH3, oxo, CN, N(CH3)2, or C1-C6alkyl. In some embodiments, R3is a C3-C5cycloalkyl wherein the C3-C5cycloalkyl is optionally substituted by one or more halo, OCH3, oxo, CN, N(CH3)2, or C1-C6alkyl. 5 In some embodiments, R3is a C3-C4cycloalkyl wherein the C3-C4cycloalkyl is optionally substituted by one or more halo, OCH3, oxo, CN, N(CH3)2, or C1-C6alkyl. In some embodiments, In some embodiments, R3is a 3- to 12-membered heterocyclyl. In some embodiments, R3is a 3- to 11-membered heterocyclyl. 10 In some embodiments, R3is a 3- to 10-membered heterocyclyl. In some embodiments, R3is a 3- to 9-membered heterocyclyl. In some embodiments, R3is a 3- to 8-membered heterocyclyl. In some embodiments, R3is a 3- to 7-membered heterocyclyl. In some embodiments, R3is a 3- to 6-membered heterocyclyl. 15 In some embodiments, R3is a 3- to 5-membered heterocyclyl. In some embodiments, R3is a 3- to 4-membered heterocyclyl. In some embodiments, R3is a 3- to 12-membered heterocyclyl, wherein the 3- to 12- membered heterocyclyl is optionally substituted by one or more R3a, wherein: each R3ais independently halo, OR4a, oxo, CN, N(R4a)(R4b), or C1-C6alkyl, and 20 wherein: each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6-C10aryl 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-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered 25 heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted with C1-C6alkoxy or C(O)N(R4a’)(R4b’); and each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl; In some embodiments, R3is a 3- to 12-membered heterocyclyl that is optionally 30 substituted by one or more R3a, wherein each R3ais independently halo, OR4a, oxo, CN, N(R4a)(R4b), or C1-C6alkyl, and wherein each R4aand R4bis H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is a 3- to 12-membered heterocyclyl that is optionally substituted by one or more R3a, wherein each R3ais independently halo, OH, oxo, CN, NH2, or C1-C6alkyl. In some embodiments, R3is a 3- to 11-membered heterocyclyl that is optionally 5 substituted by one or more R3a, wherein each R3ais independently halo, OH, oxo, CN, NH2, or C1-C6alkyl. In some embodiments, R3is a 3- to 10-membered heterocyclyl that is optionally substituted by one or more R3a, wherein each R3ais independently halo, OH, oxo, CN, NH2, or C1-C6alkyl. 10 In some embodiments, R3is a 3- to 9-membered heterocyclyl that is optionally substituted by one or more R3a, wherein each R3ais independently halo, OH, oxo, CN, NH2, or C1-C6 alkyl. In some embodiments, R3is a 3- to 8-membered heterocyclyl that is optionally substituted by one or more R3a, wherein each R3ais independently halo, OH, oxo, CN, NH2, or 15 C1-C6alkyl. In some embodiments, R3is a 3- to 7-membered heterocyclyl that is optionally substituted by one or more R3a, wherein each R3ais independently halo, OH, oxo, CN, NH2, or C1-C6alkyl. In some embodiments, R3is a 3- to 6-membered heterocyclyl that is optionally 20 substituted by one or more R3a, wherein each R3ais independently halo, OH, oxo, CN, NH2, or C1-C6alkyl. In some embodiments, R3is a 3- to 5-membered heterocyclyl that is optionally substituted by one or more R3a, wherein each R3ais independently halo, OH, oxo, CN, NH2, or C1-C6alkyl. 25 In some embodiments, R3is a 3- to 4-membered heterocyclyl that is optionally substituted by one or more R3a, wherein each R3ais independently halo, OH, oxo, CN, NH2, or C1-C6alkyl. In some embodiments, In some embodiments, R3is a 3- to 12-membered heterocyclyl that is optionally 30 substituted by one or more R3a, wherein R3ais methyl. In some embodiments, R3is a 3- to 11-membered heterocyclyl that is optionally substituted by one or more R3a, wherein R3ais methyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is a 3- to 10-membered heterocyclyl that is optionally substituted by one or more R3a, wherein R3ais methyl. In some embodiments, R3is a 3- to 9-membered heterocyclyl that is optionally substituted by one or more R3a, wherein R3ais methyl. 5 In some embodiments, R3is a 3- to 8-membered heterocyclyl that is optionally substituted by one or more R3a, wherein R3ais methyl. In some embodiments, R3is a 3- to 7-membered heterocyclyl that is optionally substituted by one or more R3a, wherein R3ais methyl. In some embodiments, R3is a 3- to 6-membered heterocyclyl that is optionally 10 substituted by one or more R3a, wherein R3ais methyl. In some embodiments, R3is a 3- to 5-membered heterocyclyl that is optionally substituted by one or more R3a, wherein R3ais methyl. In some embodiments, R3is a 3- to 4-membered heterocyclyl that is optionally substituted by one or more R3a, wherein R3ais methyl. 15 In some embodiments, In some embodiments, R3is C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more R3a, wherein: each R3ais independently OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), C1-C6alkyl, C3-C12cycloalkyl, C1-C620 alkoxy, C6-C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein the C1-C6alkyl, C3-C12cycloalkyl, C6-C10aryl, 3- to 12-membered heterocyclyl 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-C625 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocyclyl that is optionally substituted with oxo; each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6-C10aryl or N(R4a’)(R4b’); each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, 30 C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted with C1-C6alkoxy or C(O)N(R4a’)(R4b’); and Attorney Docket No. SYND-060 / 001WO 327830-2818 each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more R3a, wherein each R3ais independently oxo, CN, N(R4a)(R4b), 5 OR4a, C(O)O(R4a), S(=O)2R4b’ or C1-C6alkyl; each R4aand R4bis independently H, or C1-C6alkyl; and each R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C5alkyl, wherein the C1-C5alkyl is optionally substituted with one or more R3a, wherein each R3ais independently oxo, CN, N(R4a)(R4b), 10 OR4a, C(O)O(R4a), S(=O)2R4b’ or C1-C6alkyl; each R4aand R4bis independently H, or C1-C6alkyl; and each R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C4alkyl, wherein the C1-C4alkyl is optionally substituted with one or more R3a, wherein each R3ais independently oxo, CN, N(R4a)(R4b), 15 OR4a, C(O)O(R4a), S(=O)2R4b’ or C1-C6alkyl; each R4aand R4bis independently H, or C1-C6alkyl; and each R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C3alkyl, wherein the C1-C3alkyl is optionally substituted with one or more R3a, wherein each R3ais independently oxo, CN, N(R4a)(R4b), 20 OR4a, C(O)O(R4a), S(=O)2R4b’ or C1-C6alkyl; each R4aand R4bis independently H, or C1-C6alkyl; and each R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C2alkyl, wherein the C1-C2alkyl is optionally substituted with one or more R3a, wherein each R3ais independently oxo, CN, N(R4a)(R4b), 25 OR4a, C(O)O(R4a), S(=O)2R4b’ or C1-C6alkyl; each R4aand R4bis independently H, or C1-C6alkyl; and each R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is methyl, wherein the methyl is optionally substituted with one or more R3a, wherein each R3ais independently oxo, CN, N(R4a)(R4b), OR4a, C(O)O(R4a), 30 S(=O)2R4b’ or C1-C6alkyl; each R4aand R4bis independently H, or C1-C6alkyl; and each R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is ethyl, wherein the ethyl is optionally substituted with one or more R3a, wherein each R3ais independently oxo, CN, N(R4a)(R4b), OR4a, C(O)O(R4a), Attorney Docket No. SYND-060 / 001WO 327830-2818 S(=O)2R4b’ or C1-C6alkyl; each R4aand R4bis independently H, or C1-C6alkyl; and each R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is propyl, wherein the propyl is optionally substituted with one or more R3a, wherein each R3ais independently oxo, CN, N(R4a)(R4b), OR4a, C(O)O(R4a), 5 S(=O)2R4b’ or C1-C6alkyl; each R4aand R4bis independently H, or C1-C6alkyl; and each R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is isopropyl, wherein the isopropyl is optionally substituted with one or more R3a, wherein each R3ais independently oxo, CN, N(R4a)(R4b), OR4a, C(O)O(R4a), S(=O)2R4b’ or C1-C6alkyl; each R4aand R4bis independently H, or C1-C6alkyl; 10 and each R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is butyl, wherein the butyl is optionally substituted with one or more R3a, wherein each R3ais independently oxo, CN, N(R4a)(R4b), OR4a, C(O)O(R4a), S(=O)2R4b’ or C1-C6alkyl; each R4aand R4bis independently H, or C1-C6alkyl; and each R4b’ 15 is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is tert-butyl, wherein the tert-butyl is optionally substituted with one or more R3a, wherein each R3ais independently oxo, CN, N(R4a)(R4b), OR4a, C(O)O(R4a), S(=O)2R4b’ or C1-C6alkyl; each R4aand R4bis independently H, or C1-C6alkyl; and each R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered 20 heterocyclyl. In some embodiments, R3is pentyl, wherein the pentyl is optionally substituted with one or more R3a, wherein each R3ais independently oxo, CN, N(R4a)(R4b), OR4a, C(O)O(R4a), S(=O)2R4b’ or C1-C6alkyl; each R4aand R4bis independently H, or C1-C6alkyl; and each R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. 25 In some embodiments, R3is methyl, wherein the methyl is optionally substituted with one or more C(O)O(R4a), wherein each R4aand R4bis independently H, or C1-C6alkyl. In some embodiments, R3is ethyl, wherein the ethyl is optionally substituted with one or more C(O)O(R4a), wherein each R4aand R4bis independently H, or C1-C6alkyl. In some embodiments, R3is propyl, wherein the propyl is optionally substituted with 30 one or more C(O)O(R4a), wherein each R4aand R4bis independently H, or C1-C6alkyl. In some embodiments, R3is isopropyl, wherein the isopropyl is optionally substituted with one or more C(O)O(R4a), wherein each R4aand R4bis independently H, or C1-C6alkyl. In some embodiments, R3is butyl, wherein the butyl is optionally substituted with one or more C(O)O(R4a), wherein each R4aand R4bis independently H, or C1-C6alkyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is tert-butyl, wherein the tert-butyl is optionally substituted with one or more C(O)O(R4a), wherein each R4aand R4bis independently H, or C1-C6alkyl. In some embodiments, R3is pentyl, wherein the pentyl is optionally substituted with one or more C(O)O(R4a), wherein each R4aand R4bis independently H, or C1-C6alkyl. 5 In some embodiments, R3is -CH2-C(O)OH, -CH2-CH2-C(O)OH, or -CH2-CH2-OMe. In some embodiments, R3is methyl, wherein the methyl is optionally substituted with one or more CN. In some embodiments, R3is ethyl, wherein the ethyl is optionally substituted with one or more CN. 10 In some embodiments, R3is propyl, wherein the propyl is optionally substituted with one or more CN. In some embodiments, R3is isopropyl, wherein the isopropyl is optionally substituted with one or more CN. In some embodiments, R3is butyl, wherein the butyl is optionally substituted with one 15 or more CN. In some embodiments, R3is tert-butyl, wherein the tert-butyl is optionally substituted with one or more CN. In some embodiments, R3is pentyl, wherein the pentyl is optionally substituted with one or more CN. 20 In some embodiments, R3is -CH2-CH2-CN. In some embodiments, R3is methyl substituted with one R3a. In some embodiments, R3ais S(=O)2R4b’, wherein each R4b’ is independently H, C1-C6 alkyl, C3-C12 cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is -CH2-S(=O)2Me. In some embodiments, R3is ethyl substituted with one R3a. In some embodiments, R3a25 is S(=O)2R4b’, wherein each R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is -CH2-CH2-S(=O)2Me. In some embodiments, R3is ethyl substituted with one R3a. In some embodiments, R3ais S(=O)2R4b’, wherein each R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is -CH2-CH2-CH2-S(=O)2Me. 30 In some embodiments, R3is propyl substituted with one R3a. In some embodiments, R3ais S(=O)2R4b’, wherein each R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is isopropyl substituted with one R3a. In some embodiments, R3ais S(=O)2R4b’, wherein each R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is butyl substituted with one R3a. In some embodiments, R3a5 is S(=O)2R4b’, wherein each R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is tert-butyl substituted with one R3a. In some embodiments, R3ais S(=O)2R4b’, wherein each R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. 10 In some embodiments, R3is methyl, wherein the methyl is optionally substituted with one or more S(=O)2R4b’, wherein R4b’ is C1-C6alkyl. In some embodiments, R3is ethyl, wherein the ethyl is optionally substituted with one or more S(=O)2R4b’, wherein R4b’ is C1-C6alkyl. In some embodiments, R3is propyl, wherein the propyl is optionally substituted with 15 one or more S(=O)2R4b’, wherein R4b’ is C1-C6alkyl. In some embodiments, R3is isopropyl, wherein the isopropyl is optionally substituted with one or more S(=O)2R4b’, wherein R4b’ is C1-C6alkyl. In some embodiments, R3is butyl, wherein the butyl is optionally substituted with one or more S(=O)2R4b’, wherein R4b’ is C1-C6alkyl. 20 In some embodiments, R3is tert-butyl, wherein the tert-butyl is optionally substituted with one or more S(=O)2R4b’, wherein R4b’ is C1-C6alkyl. In some embodiments, R3is pentyl, wherein the pentyl is optionally substituted with one or more S(=O)2R4b’, wherein R4b’ is C1-C6alkyl. In some embodiments, R3is -CH2-CH2-S(=O)2Me. 25 In some embodiments, R3is -CH2-CH2-CH2-S(=O)2Me. In some embodiments, R3is methyl, wherein the methyl is optionally substituted with one or more N(R4a)(R4b), wherein each R4aand R4bis independently H, or C1-C6alkyl. In some embodiments, R3is ethyl, wherein the ethyl is optionally substituted with one or more N(R4a)(R4b), wherein each R4aand R4bis independently H, or C1-C6 alkyl. 30 In some embodiments, R3is propyl, wherein the propyl is optionally substituted with one or more N(R4a)(R4b), wherein each R4aand R4bis independently H, or C1-C6alkyl. In some embodiments, R3is isopropyl, wherein the isopropyl is optionally substituted with one or more N(R4a)(R4b), wherein each R4aand R4bis independently H, or C1-C6alkyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is butyl, wherein the butyl is optionally substituted with one or more N(R4a)(R4b), wherein each R4aand R4bis independently H, or C1-C6alkyl. In some embodiments, R3is tert-butyl, wherein the tert-butyl is optionally substituted with one or more N(R4a)(R4b), wherein each R4aand R4bis independently H, or C1-C6alkyl. 5 In some embodiments, R3is pentyl, wherein the pentyl is optionally substituted with one or more N(R4a)(R4b), wherein each R4aand R4bis independently H, or C1-C6alkyl. In some embodiments, R3is methyl, wherein the methyl is optionally substituted with one or more N(R4a)(R4b), wherein each R4ais H and each R4bis methyl. In some embodiments, R3is ethyl, wherein the ethyl is optionally substituted with one 10 or more N(R4a)(R4b), wherein each R4ais H and each R4bis methyl. In some embodiments, R3is propyl, wherein the propyl is optionally substituted with one or more N(R4a)(R4b), wherein each R4ais H and each R4bis methyl. In some embodiments, R3is isopropyl, wherein the isopropyl is optionally substituted with one or more N(R4a)(R4b), wherein each R4ais H and each R4bis methyl. 15 In some embodiments, R3is butyl, wherein the butyl is optionally substituted with one or more N(R4a)(R4b), wherein each R4ais H and each R4bis methyl. In some embodiments, R3is tert-butyl, wherein the tert-butyl is optionally substituted with one or more N(R4a)(R4b), wherein each R4ais H and each R4bis methyl. In some embodiments, R3is pentyl, wherein the pentyl is optionally substituted with 20 one or more N(R4a)(R4b), wherein each R4ais H and each R4bis methyl. In some embodiments, R3is -CH2-CH2-NH(CH3), -CH2-CH2-CH2-NH(CH3), -CH2- CH2-CH2-CH2-NH(CH3), or -CH2-CH2-CH2-CH2-CH2-NH(CH3). In some embodiments, R3is methyl, wherein the methyl is optionally substituted with one or more N(R4a)(R4b), wherein each R4ais methyl and each R4bis methyl. 25 In some embodiments, R3is ethyl, wherein the ethyl is optionally substituted with one or more N(R4a)(R4b), wherein each R4ais methyl and each R4bis methyl. In some embodiments, R3is propyl, wherein the propyl is optionally substituted with one or more N(R4a)(R4b), wherein each R4ais methyl and each R4bis methyl. In some embodiments, R3is isopropyl, wherein the isopropyl is optionally substituted 30 with one or more N(R4a)(R4b), wherein each R4ais methyl and each R4bis methyl. In some embodiments, R3is butyl, wherein the butyl is optionally substituted with one or more N(R4a)(R4b), wherein each R4ais methyl and each R4bis methyl. In some embodiments, R3is tert-butyl, wherein the tert-butyl is optionally substituted with one or more N(R4a)(R4b), wherein each R4ais methyl and each R4bis methyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is pentyl, wherein the pentyl is optionally substituted with one or more N(R4a)(R4b), wherein each R4ais methyl and each R4bis methyl. In some embodiments, R3is -CH2-CH2-N(CH3)2, -CH2-CH2-CH2-N(CH3)2, -CH2-CH2- CH2-CH2-N(CH3)2, or -CH2-CH2-CH2-CH2-CH2-N(CH3)2. 5 In some embodiments, R3is methyl, wherein the methyl is optionally substituted with one or more N(R4a)(R4b), wherein R4ais ethyl and R4bis ethyl. In some embodiments, R3is ethyl, wherein the ethyl is optionally substituted with one or more N(R4a)(R4b), wherein R4ais ethyl and R4bis ethyl. In some embodiments, R3is propyl, wherein the propyl is optionally substituted with 10 one or more N(R4a)(R4b), wherein R4ais ethyl and R4bis ethyl. In some embodiments, R3is isopropyl, wherein the isopropyl is optionally substituted with one or more N(R4a)(R4b), wherein R4ais ethyl and R4bis ethyl. In some embodiments, R3is butyl, wherein the butyl is optionally substituted with one or more N(R4a)(R4b), wherein R4ais ethyl and R4bis ethyl. 15 In some embodiments, R3is tert-butyl, wherein the tert-butyl is optionally substituted with one or more N(R4a)(R4b), wherein R4ais ethyl and R4bis ethyl. In some embodiments, R3is pentyl, wherein the pentyl is optionally substituted with one or more N(R4a)(R4b), wherein R4ais ethyl and R4bis ethyl. In some embodiments, R3is -CH2-CH2-N(CH2-CH3)2or -CH2-CH2-CH2-N(CH2-CH3)2. 20 In some embodiments, R3is methyl, wherein the methyl is optionally substituted with one or more N(R4a)(R4b), wherein R4ais H and R4bis H. In some embodiments, R3is ethyl, wherein the ethyl is optionally substituted with one or more N(R4a)(R4b), wherein R4ais H and R4bis H. In some embodiments, R3is propyl, wherein the propyl is optionally substituted with 25 one or more N(R4a)(R4b), wherein R4ais H and R4bis H. In some embodiments, R3is isopropyl, wherein the isopropyl is optionally substituted with one or more N(R4a)(R4b), wherein R4ais H and R4bis H. In some embodiments, R3is butyl, wherein the butyl is optionally substituted with one or more N(R4a)(R4b), wherein R4ais H and R4bis H. 30 In some embodiments, R3is tert-butyl, wherein the tert-butyl is optionally substituted with one or more N(R4a)(R4b), wherein R4ais H and R4bis H. In some embodiments, R3is pentyl, wherein the pentyl is optionally substituted with one or more N(R4a)(R4b), wherein R4ais H and R4bis H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is -CH2-CH2-NH2, -CH2-CH2-CH2-NH2, -CH2-CH2- C(CH3)2(NH2). In some embodiments, R3is methyl, wherein the methyl is optionally substituted with one or more OH. 5 In some embodiments, R3is ethyl, wherein the ethyl is optionally substituted with one or more OH. In some embodiments, R3is propyl, wherein the propyl is optionally substituted with one or more OH. In some embodiments, R3is isopropyl, wherein the isopropyl is optionally substituted 10 with one or more OH. In some embodiments, R3is butyl, wherein the butyl is optionally substituted with one or more OH. In some embodiments, R3is tert-butyl, wherein the tert-butyl is optionally substituted with one or more OH. 15 In some embodiments, R3is pentyl, wherein the pentyl is optionally substituted with one or more OH. In some embodiments, R3is methyl, wherein the methyl is optionally substituted with one or more OR4a, wherein R4ais H. In some embodiments, R3is ethyl, wherein the ethyl is optionally substituted with one 20 or more OR4a, wherein R4ais H. In some embodiments, R3is propyl, wherein the propyl is optionally substituted with one or more OR4a, wherein R4ais H. In some embodiments, R3is isopropyl, wherein the isopropyl is optionally substituted with one or more OR4a, wherein R4ais H. 25 In some embodiments, R3is butyl, wherein the butyl is optionally substituted with one or more OR4a, wherein R4ais H. In some embodiments, R3is tert-butyl, wherein the tert-butyl is optionally substituted with one or more OR4a, wherein R4ais H. In some embodiments, R3is pentyl, wherein the pentyl is optionally substituted with 30 one or more OR4a, wherein R4ais H. In some embodiments, R3is -CH2-CH2-OH, -CH2-CH2-CH2-OH, -CH2-CH2- C(CH3)2(OH), or -CH2-C(CH3)2(OH). Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is propyl, wherein the propyl is optionally substituted with one C1-C6alkyl and one OR4a. In some embodiments, R4ais H and C1-C6alkyl is methyl. In some embodiments, R3is -CH2-C(CH3)2(OH). In some embodiments, R3is butyl, wherein the butyl is optionally substituted with one 5 C1-C6alkyl and one OR4a. In some embodiments, R4ais H and C1-C6alkyl is methyl. In some embodiments, R3is -CH2-CH2-C(CH3)2(OH). In some embodiments, R3is ethyl, wherein the ethyl is optionally substituted with one OR4a. In some embodiments, R4ais methyl. In some embodiments, R3is propyl, wherein the propyl is optionally substituted with 10 one OR4a. In some embodiments, R4ais methyl. In some embodiments, R3is isopropyl, wherein the isopropyl is optionally substituted with one OR4a. In some embodiments, R4ais methyl. In some embodiments, R3is butyl, wherein the butyl is optionally substituted with one OR4a. In some embodiments, R4ais methyl. 15 In some embodiments, R3is tert-butyl, wherein the tert-butyl is optionally substituted with one OR4a. In some embodiments, R4ais methyl. In some embodiments, R3is pentyl, wherein the pentyl is optionally substituted with one OR4a. In some embodiments, R4ais methyl. In some embodiments, R3is methyl substituted with one R3a. In some embodiments, 20 R3ais C(O)O(R4a), wherein R4ais H, CN, or C1-C6alkyl optionally substituted with C6-C10aryl or N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is -CH2-C(O)OH. In some embodiments, R3is ethyl substituted with one R3a. In some embodiments, R3ais C(O)O(R4a), wherein R4ais H, CN, or C1-C6alkyl optionally substituted with C6-C10aryl or 25 N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is -CH2-CH2- C(O)OH. In some embodiments, R3is propyl substituted with one R3a. In some embodiments, R3ais C(O)O(R4a), wherein R4ais H, CN, or C1-C6 alkyl optionally substituted with C6-C10 aryl or 30 N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is isopropyl substituted with one R3a. In some embodiments, R3ais C(O)O(R4a), wherein R4ais H, CN, or C1-C6alkyl optionally substituted with C6-C10aryl Attorney Docket No. SYND-060 / 001WO 327830-2818 or N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is butyl substituted with one R3a. In some embodiments, R3ais C(O)O(R4a), wherein R4ais H, CN, or C1-C6alkyl optionally substituted with C6-C10aryl or 5 N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is tert-butyl substituted with one R3a. In some embodiments, R3ais C(O)O(R4a), wherein R4ais H, CN, or C1-C6alkyl optionally substituted with C6-C10aryl or N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C1210 cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more R3a, wherein each R3ais independently C6-C10 aryl that is optionally substituted with one or more C(O)OR4a’, and wherein R4a’ is H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. 15 In some embodiments, R3is C1-C5alkyl, wherein the C1-C5alkyl is optionally substituted with one or more R3a, wherein each R3ais independently C6-C10aryl that is optionally substituted with one or more C(O)OR4a’, and wherein R4a’ is H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C4alkyl, wherein the C1-C4alkyl is optionally 20 substituted with one or more R3a, wherein each R3ais independently C6-C10aryl that is optionally substituted with one or more C(O)OR4a’, and wherein R4a’ is H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C3alkyl, wherein the C1-C3alkyl is optionally substituted with one or more R3a, wherein each R3ais independently C6-C10aryl that is 25 optionally substituted with one or more C(O)OR4a’, and wherein R4a’ is H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C2alkyl, wherein the C1-C2alkyl is optionally substituted with one or more R3a, wherein each R3ais independently C6-C10aryl that is optionally substituted with one or more C(O)OR4a’, and wherein R4a’ is H, C1-C6 alkyl, C3-C12 30 cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is methyl that is optionally substituted with one or more R3a, wherein each R3ais independently C6-C10aryl that is optionally substituted with one or more Attorney Docket No. SYND-060 / 001WO 327830-2818 C(O)OR4a’, and wherein R4a’ is H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is . In some embodiments, R3is ethyl that is optionally substituted with one or more R3a, wherein each R3ais independently C6-C10aryl that is optionally substituted with one or more 5 C(O)OR4a’, and wherein R4a’ is H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is propyl that is optionally substituted with one or more R3a, wherein each R3ais independently C6-C10aryl that is optionally substituted with one or more C(O)OR4a’, and wherein R4a’ is H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered 10 heterocyclyl. In some embodiments, R3is isopropyl that is optionally substituted with one or more R3a, wherein each R3ais independently C6-C10aryl that is optionally substituted with one or more C(O)OR4a’, and wherein R4a’ is H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. 15 In some embodiments, R3is butyl that is optionally substituted with one or more R3a, wherein each R3ais independently C6-C10aryl that is optionally substituted with one or more C(O)OR4a’, and wherein R4a’ is H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C6alkyl, wherein the C1-C6alkyl is optionally 20 substituted with one or more R3a, wherein each R3ais independently 5- to 10-membered heteroaryl that is optionally substituted with one or more C1-C6alkyl. In some embodiments, R3is C1-C5alkyl, wherein the C1-C5alkyl is optionally substituted with one or more R3a, wherein each R3ais independently 5- to 10-membered heteroaryl that is optionally substituted with one or more C1-C6alkyl. 25 In some embodiments, R3is C1-C4alkyl, wherein the C1-C4alkyl is optionally substituted with one or more R3a, wherein each R3ais independently 5- to 10-membered heteroaryl that is optionally substituted with one or more C1-C6alkyl. In some embodiments, R3is C1-C3alkyl, wherein the C1-C3alkyl is optionally substituted with one or more R3a, wherein each R3ais independently 5- to 10-membered 30 heteroaryl that is optionally substituted with one or more C1-C6alkyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is C1-C2alkyl, wherein the C1-C2alkyl is optionally substituted with one or more R3a, wherein each R3ais independently 5- to 10-membered heteroaryl that is optionally substituted with one or more C1-C6alkyl. In some embodiments, R3is methyl that is optionally substituted with one or more R3a, 5 wherein each R3ais independently 5- to 10-membered heteroaryl that is optionally substituted with one or more C1-C6alkyl. In some embodiments, R3is , In some embodiments, R3is ethyl that is optionally substituted with one or more R3a, wherein each R3ais independently 5- to 10-membered heteroaryl that is optionally substituted 10 with one or more C1-C6alkyl. In some embodiments, R3is propyl that is optionally substituted with one or more R3a, wherein each R3ais independently 5- to 10-membered heteroaryl that is optionally substituted with one or more C1-C6alkyl. In some embodiments, R3is isopropyl that is optionally substituted with one or more 15 R3a, wherein each R3ais independently 5- to 10-membered heteroaryl that is optionally substituted with one or more C1-C6alkyl. In some embodiments, R3is butyl that is optionally substituted with one or more R3a, wherein each R3ais independently 5- to 10-membered heteroaryl that is optionally substituted with one or more C1-C6alkyl. 20 In some embodiments, R3is C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more R3a, wherein each R3ais independently OR4aor 5- to 10-membered heteroaryl. In some embodiments, each R4ais independently H, or C1-C6alkyl. In some embodiments, R3is C1-C5alkyl, wherein the C1-C5alkyl is optionally substituted with one or more R3a, wherein each R3ais independently OR4aor 5- to 10-membered 25 heteroaryl. In some embodiments, each R4ais independently H, or C1-C6alkyl. In some embodiments, R3is C1-C4alkyl, wherein the C1-C4alkyl is optionally substituted with one or more R3a, wherein each R3ais independently OR4aor 5- to 10-membered heteroaryl. In some embodiments, each R4ais independently H, or C1-C6alkyl. In some embodiments, R3is C1-C3alkyl, wherein the C1-C3alkyl is optionally 30 substituted with one or more R3a, wherein each R3ais independently OR4aor 5- to 10-membered heteroaryl. In some embodiments, each R4ais independently H, or C1-C6alkyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is C1-C2alkyl, wherein the C1-C2alkyl is optionally substituted with one or more R3a, wherein each R3ais independently OR4aor 5- to 10-membered heteroaryl. In some embodiments, each R4ais independently H, or C1-C6alkyl. In some embodiments, R3is C1-C6alkyl, wherein the C1-C6alkyl is substituted with 5 one OR4aand one 5- to 10-membered heteroaryl. In some embodiments, R4ais H. In some embodiments, R3is C1-C5alkyl, wherein the C1-C5alkyl is substituted with one OR4aand one 5- to 10-membered heteroaryl. In some embodiments, R4ais H. In some embodiments, R3is C1-C4alkyl, wherein the C1-C4alkyl is substituted with one OR4aand one 5- to 10-membered heteroaryl. In some embodiments, R4ais H. 10 In some embodiments, R3is C1-C3alkyl, wherein the C1-C3alkyl is substituted with one OR4aand one 5- to 10-membered heteroaryl. In some embodiments, R4ais H. In some embodiments, R3is C1-C2 alkyl, wherein the C1-C2 alkyl is substituted with one OR4aand one 5- to 10-membered heteroaryl. In some embodiments, R4ais H. In some embodiments, R3is methyl that is substituted with one OR4aand one 5- to 10- 15 membered heteroaryl. In some embodiments, R4ais H. In some embodiments, R3is ethyl that is substituted with one OR4aand one 5- to 10- membered heteroaryl. In some embodiments, R4ais H. In some embodiments, R3is propyl that is substituted with one OR4aand one 5- to 10- membered heteroaryl. In some embodiments, R4ais H. In some embodiments, R3is 20 In some embodiments, R3is isopropyl that is substituted with one OR4aand one 5- to 10-membered heteroaryl. In some embodiments, R4ais H. In some embodiments, R3is butyl that is substituted with one OR4aand one 5- to 10- membered heteroaryl. In some embodiments, R4ais H. 25 In some embodiments, R3is C1-C6alkyl, wherein the C1-C6alkyl is substituted with one OR4aand one 5- to 10-membered heteroaryl. In some embodiments, R4ais methyl. In some embodiments, R3is C1-C5alkyl, wherein the C1-C5alkyl is substituted with one OR4aand one 5- to 10-membered heteroaryl. In some embodiments, R4ais methyl. In some embodiments, R3is C1-C4 alkyl, wherein the C1-C4 alkyl is substituted with 30 one OR4aand one 5- to 10-membered heteroaryl. In some embodiments, R4ais methyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is C1-C3alkyl, wherein the C1-C3alkyl is substituted with one OR4aand one 5- to 10-membered heteroaryl. In some embodiments, R4ais methyl. In some embodiments, R3is C1-C2alkyl, wherein the C1-C2alkyl is substituted with one OR4aand one 5- to 10-membered heteroaryl. In some embodiments, R4ais methyl. 5 In some embodiments, R3is methyl that is substituted with one OR4aand one 5- to 10- membered heteroaryl. In some embodiments, R4ais methyl. In some embodiments, R3is ethyl that is substituted with one OR4aand one 5- to 10- membered heteroaryl. In some embodiments, R4ais methyl. In some embodiments, R3is propyl that is substituted with one OR4aand one 5- to 10- 10 membered heteroaryl. In some embodiments, R4ais methyl. In some embodiments, R3is In some embodiments, R3is isopropyl that is substituted with one OR4aand one 5- to 10-membered heteroaryl. In some embodiments, R4ais methyl. In some embodiments, R3is butyl that is substituted with one OR4aand one 5- to 10- 15 membered heteroaryl. In some embodiments, R4ais methyl. In some embodiments, R3is C1-C6alkyl that is optionally substituted with one or more R3a, wherein R3ais OR4a. In some embodiments, each R4ais independently C1-C6alkyl optionally substituted with N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. 20 In some embodiments, R3is C1-C5alkyl that is optionally substituted with one or more R3a, wherein R3ais OR4a. In some embodiments, each R4ais independently C1-C6 alkyl optionally substituted with N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is C1-C4alkyl that is optionally substituted with one or more 25 R3a, wherein R3ais OR4a. In some embodiments, each R4ais independently C1-C6alkyl optionally substituted with N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is C1-C3 alkyl that is optionally substituted with one or more R3a, wherein R3ais OR4a. In some embodiments, each R4ais independently C1-C6alkyl 30 optionally substituted with N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is C1-C2alkyl that is optionally substituted with one or more R3a, wherein R3ais OR4a. In some embodiments, each R4ais independently C1-C6alkyl optionally substituted with N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. 5 In some embodiments, R3is methyl that is optionally substituted with one or more R3a, wherein R3ais OR4a. In some embodiments, each R4ais independently C1-C6alkyl optionally substituted with N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is ethyl that is optionally substituted with one or more R3a, 10 wherein R3ais OR4a. In some embodiments, each R4ais independently C1-C6alkyl optionally substituted with N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is . In some embodiments, R3is propyl that is optionally substituted with one or more R3a, wherein R3ais OR4a. In some embodiments, each R4ais independently C1-C6alkyl optionally 15 substituted with N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H or C1-C6 alkyl. In some embodiments, R3is isopropyl that is optionally substituted with one or more R3a, wherein R3ais OR4a. In some embodiments, each R4ais independently C1-C6alkyl optionally substituted with N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H or 20 C1-C6alkyl. In some embodiments, R3is butyl that is optionally substituted with one or more R3a, wherein R3ais OR4a. In some embodiments, each R4ais independently C1-C6alkyl optionally substituted with N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. 25 In some embodiments, R3is C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b), and wherein each R4aand R4bis independently H, or C1-C6alkyl. In some embodiments, R3is C1-C5alkyl, wherein the C1-C5alkyl is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b), and wherein each R4aand R4bis 30 independently H, or C1-C6alkyl. In some embodiments, R3is C1-C4alkyl, wherein the C1-C4alkyl is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b), and wherein each R4aand R4bis independently H, or C1-C6alkyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is C1-C3alkyl, wherein the C1-C3alkyl is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b), and wherein each R4aand R4bis independently H, or C1-C6alkyl. In some embodiments, R3is C1-C2alkyl, wherein the C1-C2alkyl is optionally 5 substituted with one or more R3a, wherein R3ais N(R4a)(R4b), and wherein each R4aand R4bis independently H, or C1-C6alkyl. In some embodiments, R3is methyl, wherein the methyl is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b), and wherein each R4aand R4bis independently H, or C1-C6alkyl. In some embodiments, each R4aand R4bis independently selected from the 10 group consisting of H, methyl or ethyl. In some embodiments, R3is ethyl, wherein the ethyl is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b), and wherein each R4aand R4bis independently H, or C1-C6alkyl. In some embodiments, each R4aand R4bis independently selected from the group consisting of H, methyl or ethyl. In some embodiments, R3is -CH2-CH2-NH2, -CH2-CH2- 15 NH(CH3), -CH2-CH2-N(CH3)2, or -CH2-CH2-N(CH2-CH3)2. In some embodiments, R3is ethyl, wherein the ethyl is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b), and wherein each R4aand R4bis independently H, or C1-C6alkyl that is optionally substituted with O(R4a’), and wherein R4a’ is H, or C1-C6alkyl. In some embodiments, each R4aand R4bis independently selected from the group consisting of 20 H, methyl or ethyl. In some embodiments, O(R4a’) is C1-C6alkoxy. In some embodiments, R3 In some embodiments, R3is propyl, wherein the propyl is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b), and wherein each R4aand R4bis independently H, or C1-C6alkyl. In some embodiments, each R4aand R4bis independently selected from the25 group consisting of H, methyl or ethyl. In some embodiments, R3is -CH2-CH2-CH2-NH2, - CH2-CH2-CH2-NH(CH3), -CH2-CH2-CH2-N(CH3)2, or -CH2-CH2-CH2-N(CH2-CH3)2. In some embodiments, R3is propyl, wherein the propyl is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b), wherein each R4aand R4bis independently H, or C1-C6alkyl that is optionally substituted with O(R4a’), and wherein each R4a’ is independently 30 H, or C1-C6alkyl. In some embodiments, each R4aand R4bis independently selected from the Attorney Docket No. SYND-060 / 001WO 327830-2818 group consisting of H, methyl or ethyl. In some embodiments, O(R4a’) is C1-C6alkoxy. In some embodiments, In some embodiments, R3is isopropyl, wherein the isopropyl is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b), and wherein each R4aand R4bis 5 independently H, or C1-C6alkyl. In some embodiments, each R4aand R4bis independently selected from the group consisting of H, methyl or ethyl. In some embodiments, R3is - CH(CH3)(CH2-NH2), -CH(CH3)(CH2-NH(CH3)), -CH(CH3)(CH2-N(CH3)2), or - CH(CH3)(CH2-N(CH2-CH3)2). In some embodiments, R3is butyl, wherein the butyl is optionally substituted with one 10 or more R3a, wherein R3ais N(R4a)(R4b), and wherein each R4aand R4bis independently H, or C1-C6alkyl. In some embodiments, each R4aand R4bis independently selected from the group consisting of H, methyl or ethyl. In some embodiments, R3is -CH2-CH2-CH2-CH2-NH2, -CH2- CH2-CH2-CH2-NH(CH3), -CH2-CH2-CH2-CH2-N(CH3)2, -CH2-CH2-CH2-CH2-N(CH2-CH3)2, or -CH2-CH2-C(CH3)2(NH2). 15 In some embodiments, R3is tert-butyl, wherein the tert-butyl is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b), and wherein each R4aand R4bis independently H, or C1-C6alkyl. In some embodiments, each R4aand R4bis independently selected from the group consisting of H, methyl or ethyl. In some embodiments, R3is pentyl, wherein the pentyl is optionally substituted with 20 one or more R3a, wherein R3ais N(R4a)(R4b), and wherein each R4aand R4bis independently H, or C1-C6alkyl. In some embodiments, each R4aand R4bis independently selected from the group consisting of H, methyl or ethyl. In some embodiments, R3is -CH2-CH2-CH2-CH2-CH2- NH2, -CH2-CH2-CH2-CH2-CH2-NH(CH3), -CH2-CH2-CH2-CH2-CH2-N(CH3)2, or -CH2-CH2- CH2-CH2-CH2-N(CH2-CH3)2. 25 In some embodiments, R3is C1-C6alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b), wherein: each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6-C10aryl or N(R4a’)(R4b’); each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, 30 C(O)CH2-N(R4a’)(R4b’), C1-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted with C1-C6alkoxy or C(O)N(R4a’)(R4b’); and Attorney Docket No. SYND-060 / 001WO 327830-2818 each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl. In some embodiments, R3is C1-C6alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis S(=O)2R4b’, wherein 5 each R4b’ is independently C1-C6alkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C5alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis S(=O)2R4b’, wherein each R4b’ is independently C1-C6alkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C4alkyl that is optionally substituted with one or more 10 R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis S(=O)2R4b’, wherein each R4b’ is independently C1-C6alkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C3 alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis S(=O)2R4b’, wherein each R4b’ is independently C1-C6alkyl, or 3- to 12-membered heterocyclyl. 15 In some embodiments, R3is C1-C2alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis S(=O)2R4b’, wherein each R4b’ is independently C1-C6alkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is methyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis S(=O)2R4b’, wherein 20 each R4b’ is independently C1-C6alkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is ethyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis S(=O)2R4b’, wherein each R4b’ is independently C1-C6alkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is propyl that is optionally substituted with one or more R3a, 25 wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis S(=O)2R4b’, wherein each R4b’ is independently C1-C6alkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is In some embodiments, R3is isopropyl that is that is optionally substituted with one or 30 more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis S(=O)2R4b’, wherein each R4b’ is independently C1-C6alkyl, or 3- to 12-membered heterocyclyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is butyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis S(=O)2R4b’, wherein each R4b’ is independently C1-C6alkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C6alkyl that is optionally substituted with one or more 5 R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)OR4b’, wherein R4b’ is C1-C6alkyl. In some embodiments, R3is C1-C5alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)OR4b’, wherein R4b’ is C1-C6alkyl. 10 In some embodiments, R3is C1-C4alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)OR4b’, wherein R4b’ is C1-C6 alkyl. In some embodiments, R3is C1-C3alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)OR4b’, wherein 15 R4b’ is C1-C6alkyl. In some embodiments, R3is C1-C2alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)OR4b’, wherein R4b’ is C1-C6alkyl. In some embodiments, R3is methyl that is optionally substituted with one or more R3a, 20 wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)OR4b’, wherein R4b’ is C1-C6alkyl. In some embodiments, R3is ethyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)OR4b’, wherein R4b’ is C1-C6alkyl. In some embodiments, R3is . 25 In some embodiments, R3is propyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)OR4b’, wherein R4b’ is C1-C6alkyl. In some embodiments, R3is , Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is isopropyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)OR4b’, wherein R4b’ is C1-C6alkyl. In some embodiments, R3is butyl that is optionally substituted with one or more R3a, 5 wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)OR4b’, wherein R4b’ is C1-C6alkyl. In some embodiments, R3is C1-C6alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis 5- to 10-membered heteroaryl. 10 In some embodiments, R3is C1-C5alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis 5- to 10-membered heteroaryl. In some embodiments, R3is C1-C4alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis 5- to 10-membered 15 heteroaryl. In some embodiments, R3is C1-C3alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis 5- to 10-membered heteroaryl. In some embodiments, R3is C1-C2alkyl that is optionally substituted with one or more 20 R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis 5- to 10-membered heteroaryl. In some embodiments, R3is methyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis 5- to 10-membered heteroaryl. 25 In some embodiments, R3is ethyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis 5- to 10-membered heteroaryl. In some embodiments, R3is propyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis 5- to 10-membered 30 heteroaryl. In some embodiments, R3is . Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is isopropyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis 5- to 10-membered heteroaryl. In some embodiments, R3is butyl that is optionally substituted with one or more R3a, 5 wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis 5- to 10-membered heteroaryl. In some embodiments, R3is C1-C6alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)NR4a’R4b’, wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. 10 In some embodiments, R3is C1-C5alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)NR4a’R4b’, wherein each R4a’ and R4b’ is independently H or C1-C6 alkyl. In some embodiments, R3is C1-C4alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)NR4a’R4b’, 15 wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is C1-C3alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)NR4a’R4b’, wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is C1-C2alkyl that is optionally substituted with one or more 20 R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)NR4a’R4b’, wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is methyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)NR4a’R4b’, wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. 25 In some embodiments, R3is ethyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)NR4a’R4b’, wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is propyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)NR4a’R4b’, wherein 30 each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is isopropyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)NR4a’R4b’, wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is butyl that is optionally substituted with one or more R3a, 5 wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)NR4a’R4b’, wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is C1-C6alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)R4b’, wherein each R4b’ is independently H or C1-C6alkyl. 10 In some embodiments, R3is C1-C5alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)R4b’, wherein each R4b’ is independently H or C1-C6 alkyl. In some embodiments, R3is C1-C4alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)R4b’, wherein 15 each R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is C1-C3alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)R4b’, wherein each R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is C1-C2alkyl that is optionally substituted with one or more 20 R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)R4b’, wherein each R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is methyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)R4b’, wherein each R4b’ is independently H or C1-C6alkyl. 25 In some embodiments, R3is ethyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)R4b’, wherein each R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is propyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)R4b’, wherein each 30 R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is . Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is isopropyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)R4b’, wherein each R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is butyl that is optionally substituted with one or more R3a, 5 wherein R3ais N(R4a)(R4b). In some embodiments, R4ais H and R4bis C(O)R4b’, wherein each R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is C1-C6alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C(O)CH2- N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. 10 In some embodiments, R3is C1-C5alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C(O)CH2- N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H or C1-C6 alkyl. In some embodiments, R3is C1-C4alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C(O)CH2- 15 N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is C1-C3alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C(O)CH2- N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is C1-C2alkyl that is optionally substituted with one or more20 R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C(O)CH2- N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is methyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C(O)CH2- N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. 25 In some embodiments, R3is ethyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C(O)CH2- N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, In some embodiments, R3is propyl that is optionally substituted with one or more R3a,30 wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C(O)CH2- N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is isopropyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C(O)CH2- N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is butyl that is optionally substituted with one or more R3a, 5 wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C(O)CH2- N(R4a’)(R4b’), wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is C1-C6alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C1-C6alkyl that is optionally substituted with C1-C6alkoxy. 10 In some embodiments, R3is C1-C5alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C1-C6alkyl that is optionally substituted with C1-C6 alkoxy. In some embodiments, R3is C1-C4alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C1-C6alkyl 15 that is optionally substituted with C1-C6alkoxy. In some embodiments, R3is C1-C3alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C1-C6alkyl that is optionally substituted with C1-C6alkoxy. In some embodiments, R3is C1-C2alkyl that is optionally substituted with one or more 20 R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C1-C6alkyl that is optionally substituted with C1-C6alkoxy. In some embodiments, R3is methyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C1-C6alkyl that is optionally substituted with C1-C6alkoxy. 25 In some embodiments, R3is ethyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C1-C6alkyl that is optionally substituted with C1-C6alkoxy. In some embodiments, R3is . In some embodiments, R3is propyl that is optionally substituted with one or more R3a, 30 wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C1-C6alkyl that is optionally substituted with C1-C6alkoxy. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is isopropyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C1-C6alkyl that is optionally substituted with C1-C6alkoxy. In some embodiments, R3is butyl that is optionally substituted with one or more R3a, 5 wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C1-C6alkyl that is optionally substituted with C1-C6alkoxy. In some embodiments, R3is C1-C6alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C1-C6alkyl that is optionally substituted with C(O)N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is 10 independently H or C1-C6alkyl. In some embodiments, R3is C1-C5alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6 alkyl and R4bis C1-C6 alkyl that is optionally substituted with C(O)N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. 15 In some embodiments, R3is C1-C4alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C1-C6alkyl that is optionally substituted with C(O)N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is C1-C3alkyl that is optionally substituted with one or more 20 R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C1-C6alkyl that is optionally substituted with C(O)N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H or C1-C6 alkyl. In some embodiments, R3is C1-C2alkyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C1-C6alkyl 25 that is optionally substituted with C(O)N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is methyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C1-C6alkyl that is optionally substituted with C(O)N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is 30 independently H or C1-C6alkyl. In some embodiments, R3is ethyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C1-C6alkyl that is optionally substituted with C(O)N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is propyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C1-C6alkyl that is optionally substituted with C(O)N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is . 5 In some embodiments, R3is isopropyl that is optionally substituted with one or more R3a, wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C1-C6alkyl that is optionally substituted with C(O)N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is butyl that is optionally substituted with one or more R3a, 10 wherein R3ais N(R4a)(R4b). In some embodiments, R4ais C1-C6alkyl and R4bis C1-C6alkyl that is optionally substituted with C(O)N(R4a’)(R4b’) and wherein each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is C1-C6alkyl that is optionally substituted with one or more R3a, wherein R3ais C(=O)N(R4a)(R4b). In some embodiments, each R4aand R4bis independently 15 H or C1-C6 alkyl. In some embodiments, R3is C1-C5alkyl that is optionally substituted with one or more R3a, wherein R3ais C(=O)N(R4a)(R4b). In some embodiments, each R4aand R4bis independently H or C1-C6alkyl. In some embodiments, R3is C1-C4alkyl that is optionally substituted with one or more 20 R3a, wherein R3ais C(=O)N(R4a)(R4b). In some embodiments, each R4aand R4bis independently H or C1-C6alkyl. In some embodiments, R3is C1-C3alkyl that is optionally substituted with one or more R3a, wherein R3ais C(=O)N(R4a)(R4b). In some embodiments, each R4aand R4bis independently H or C1-C6alkyl. 25 In some embodiments, R3is C1-C2 alkyl that is optionally substituted with one or more R3a, wherein R3ais C(=O)N(R4a)(R4b). In some embodiments, each R4aand R4bis independently H or C1-C6alkyl. In some embodiments, R3is methyl that is optionally substituted with one or more R3a, wherein R3ais C(=O)N(R4a)(R4b). In some embodiments, each R4aand R4bis independently H 30 or C1-C6alkyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is ethyl that is optionally substituted with one or more R3a, wherein R3ais C(=O)N(R4a)(R4b). In some embodiments, each R4aand R4bis independently H or C1-C6alkyl. In some embodiments, R3is . In some embodiments, R3is propyl that is optionally substituted with one or more R3a, 5 wherein R3ais C(=O)N(R4a)(R4b). In some embodiments, each R4aand R4bis independently H or C1-C6alkyl. In some embodiments, R3is isopropyl that is optionally substituted with one or more R3a, wherein R3ais C(=O)N(R4a)(R4b). In some embodiments, each R4aand R4bis independently H or C1-C6alkyl. 10 In some embodiments, R3is butyl that is optionally substituted with one or more R3a, wherein R3ais C(=O)N(R4a)(R4b). In some embodiments, each R4aand R4bis independently H or C1-C6alkyl. In some embodiments, R3is C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more R3a, wherein: 15 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-C6alkyl, C3-C12cycloalkyl, C1-C6alkoxy, C6- C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein the C1-C6alkyl, C3-C12cycloalkyl, C6-C10aryl, 3- to 12-membered heterocyclyl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from 20 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-C6alkyl that is optionally substituted with O(R4a), and 3- to 12- membered heterocyclyl that is optionally substituted with oxo; each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6-C10aryl or N(R4a’)(R4b’); 25 each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), C1-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted with C1-C6alkoxy or C(O)N(R4a’)(R4b’); and each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- 30 membered heterocyclyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is C1-C6alkyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more C1-C6alkyl. In some embodiments, R3is C1-C5alkyl that is optionally substituted with one or more 5 R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more C1-C6alkyl. In some embodiments, R3is C1-C4alkyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more C1-C6alkyl. 10 In some embodiments, R3is C1-C3alkyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more C1-C6 alkyl. In some embodiments, R3is C1-C2alkyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally 15 substituted with one or more C1-C6alkyl. In some embodiments, R3is methyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more C1-C6alkyl. In some embodiments, R3is , , 20 , In some embodiments, R3is ethyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more C1-C6alkyl. In some embodiments, R3is , Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is propyl that is optionally substituted with one or more R3a, 5 wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted 10 In some embodiments, R3is isopropyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more C1-C6alkyl. In some embodiments, R3is butyl that is optionally substituted with one or more R3a, 15 wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more C1-C6alkyl. In some embodiments, R3is tert-butyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more C1-C6alkyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is pentyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more C1-C6alkyl. In some embodiments, R3is methyl that is optionally substituted with one or more R3a, 5 wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one O(R4a’). In some embodiments, R4a’ is H. In some embodiments, R3is ethyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one O(R4a’). In some embodiments, R4a’ is H. 10 In some embodiments, R3is propyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one O(R4a’). In some embodiments, R4a’ is H. In some embodiments, R3is , 15 In some embodiments, R3is isopropyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one O(R4a’). In some embodiments, R4a’ is H. In some embodiments, R3is butyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted 20 with one O(R4a’). In some embodiments, R4a’ is H. In some embodiments, R3is C1-C6alkyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more oxo. In some embodiments, R3is C1-C5alkyl that is optionally substituted with one or more 25 R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more oxo. In some embodiments, R3is C1-C4alkyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more oxo. 30 In some embodiments, R3is C1-C3alkyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more oxo. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is C1-C2alkyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more oxo. In some embodiments, R3is methyl that is substituted with one or more R3a, wherein 5 each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more oxo. In some embodiments, R3is ethyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more oxo. 10 In some embodiments, R3is propyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more oxo. In some embodiments, R3is , 15 In some embodiments, R3is isopropyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more oxo. In some embodiments, R3is butyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or 20 more oxo. In some embodiments, R3is C1-C6alkyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more oxo and one or more C1-C6alkyl. In some embodiments, R3is C1-C5alkyl that is optionally substituted with one or more 25 R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more oxo and one or more C1-C6alkyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is C1-C4alkyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more oxo and one or more C1-C6alkyl. In some embodiments, R3is C1-C3alkyl that is optionally substituted with one or more 5 R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more oxo and one or more C1-C6alkyl. In some embodiments, R3is C1-C2alkyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more oxo and one or more C1-C6alkyl. 10 In some embodiments, R3is methyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more oxo and one or more C1-C6 alkyl. In some embodiments, R3is ethyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted 15 with one or more oxo and one or more C1-C6alkyl. In some embodiments, R3is propyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more oxo and one or more C1-C6alkyl. In some embodiments, R3is 20 In some embodiments, R3is isopropyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more oxo and one or more C1-C6alkyl. In some embodiments, R3is butyl that is optionally substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted 25 with one or more oxo and one or more C1-C6alkyl. In some embodiments, R3is C1-C6alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more O(R4a’) or C1-C6alkyl that is optionally substituted with O(R4a). In some embodiments, R4aand R4a’ are each independently H or C1-C6 alkyl. 30 In some embodiments, R3is C1-C5alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted Attorney Docket No. SYND-060 / 001WO 327830-2818 with one or more O(R4a’) or C1-C6alkyl that is optionally substituted with O(R4a). In some embodiments, R4aand R4a’ are each independently H or C1-C6alkyl. In some embodiments, R3is C1-C4alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted 5 with one or more O(R4a’) or C1-C6alkyl that is optionally substituted with O(R4a). In some embodiments, R4aand R4a’ are each independently H or C1-C6alkyl. In some embodiments, R3is C1-C3alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more O(R4a’) or C1-C6alkyl that is optionally substituted with O(R4a). In some 10 embodiments, R4aand R4a’ are each independently H or C1-C6alkyl. In some embodiments, R3is C1-C2alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more O(R4a’) or C1-C6alkyl that is optionally substituted with O(R4a). In some embodiments, R4aand R4a’ are each independently H or C1-C6alkyl. 15 In some embodiments, R3is methyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more O(R4a’) or C1-C6alkyl that is optionally substituted with O(R4a). In some embodiments, R4aand R4a’ are each independently H or C1-C6alkyl. In some embodiments, R3is ethyl that is substituted with one or more R3a, wherein each 20 R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more O(R4a’) or C1-C6alkyl that is optionally substituted with O(R4a). In some embodiments, R4aand R4a’ are each independently H or C1-C6 alkyl. In some embodiments, R3is propyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with 25 one or more O(R4a’) or C1-C6alkyl that is optionally substituted with O(R4a). In some embodiments, R4aand R4a’ are each independently H or C1-C6alkyl. In some embodiments, R3 Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is isopropyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more O(R4a’) or C1-C6alkyl that is optionally substituted with O(R4a). In some embodiments, R4aand R4a’ are each independently H or C1-C6alkyl. 5 In some embodiments, R3is butyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more O(R4a’) or C1-C6alkyl that is optionally substituted with O(R4a). In some embodiments, R4aand R4a’ are each independently H or C1-C6alkyl. In some embodiments, R3is C1-C6alkyl that is substituted with one or more R3a, 10 wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more -CN or C1-C6alkyl. In some embodiments, R3is C1-C5 alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more -CN or C1-C6alkyl. 15 In some embodiments, R3is C1-C4alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more -CN or C1-C6alkyl. In some embodiments, R3is C1-C3alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted 20 with one or more -CN or C1-C6alkyl. In some embodiments, R3is C1-C2alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more -CN or C1-C6alkyl. In some embodiments, R3is methyl that is substituted with one or more R3a, wherein 25 each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more -CN or C1-C6alkyl. In some embodiments, R3is ethyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more -CN or C1-C6 alkyl. 30 In some embodiments, R3is propyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with Attorney Docket No. SYND-060 / 001WO 327830-2818 one or more -CN or C1-C6alkyl. In some embodiments, R3is , In some embodiments, R3is isopropyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with 5 one or more -CN or C1-C6alkyl. In some embodiments, R3is butyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more -CN or C1-C6alkyl. In some embodiments, R3is C1-C6alkyl that is substituted with one or more R3a, 10 wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more halo. In some embodiments, R3is C1-C5alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more halo. 15 In some embodiments, R3is C1-C4alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more halo. In some embodiments, R3is C1-C3alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted 20 with one or more halo. In some embodiments, R3is C1-C2alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more halo. In some embodiments, R3is methyl that is substituted with one or more R3a, wherein 25 each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more halo. In some embodiments, R3is ethyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more halo. 30 In some embodiments, R3is propyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with Attorney Docket No. SYND-060 / 001WO 327830-2818 one or more halo. In some embodiments, R3is , In some embodiments, R3is isopropyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with 5 one or more halo. In some embodiments, R3is butyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more halo. In some embodiments, R3is C1-C6alkyl that is substituted with one or more R3a, 10 wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more N(R4a’)(R4b’) and one or more C1-C6alkyl. In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C5alkyl that is substituted with one or more R3a, 15 wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more N(R4a’)(R4b’) and one or more C1-C6alkyl. In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C4alkyl that is substituted with one or more R3a, 20 wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more N(R4a’)(R4b’) and one or more C1-C6alkyl. In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C3alkyl that is substituted with one or more R3a, 25 wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more N(R4a’)(R4b’) and one or more C1-C6alkyl. In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C2alkyl that is substituted with one or more R3a, 30 wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more N(R4a’)(R4b’) and one or more C1-C6alkyl. In some embodiments, each R4a’ Attorney Docket No. SYND-060 / 001WO 327830-2818 and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is methyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with 5 one or more N(R4a’)(R4b’) and one or more C1-C6alkyl. In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is ethyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more N(R4a’)(R4b’) and one or more C1-C6alkyl. In some embodiments, each R4a’ and R4b’ is 10 independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is propyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more N(R4a’)(R4b’) and one or more C1-C6alkyl. In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In 15 some embodiments, In some embodiments, R3is isopropyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more N(R4a’)(R4b’) and one or more C1-C6alkyl. In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. 20 In some embodiments, R3is butyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one or more N(R4a’)(R4b’) and one or more C1-C6alkyl. In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C6alkyl that is substituted with one or more R3a, 25 wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C5alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted 30 with one N(R4a’)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is C1-C4alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. 5 In some embodiments, R3is C1-C3alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C2alkyl that is substituted with one or more R3a, 10 wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12 cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is methyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with 15 one N(R4a’)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is ethyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3- 20 C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is propyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is 25 . In some embodiments, R3is isopropyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. 30 In some embodiments, R3is butyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3- C12cycloalkyl, or 3- to 12-membered heterocyclyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is C1-C6alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1- C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. 5 In some embodiments, R3is C1-C5alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1- C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C4alkyl that is substituted with one or more R3a, 10 wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1- C6 alkyl, C3-C12 cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C3alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted15 with one N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1- C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C2alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1- 20 C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is methyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. 25 In some embodiments, R3is ethyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is propyl that is substituted with one or more R3a, wherein 30 each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6 Attorney Docket No. SYND-060 / 001WO 327830-2818 alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is In some embodiments, R3is isopropyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with 5 one N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is butyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, 10 C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C6alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)C(O)O(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. 15 In some embodiments, R3is C1-C5alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)C(O)O(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C4alkyl that is substituted with one or more R3a, 20 wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)C(O)O(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C3alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted 25 with one N(R4a’)C(O)O(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C2alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)C(O)O(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, 30 C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is methyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with Attorney Docket No. SYND-060 / 001WO 327830-2818 one N(R4a’)C(O)O(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is ethyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one 5 N(R4a’)C(O)O(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is propyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)C(O)O(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C610 alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is In some embodiments, R3is isopropyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)C(O)O(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C615 alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. In some embodiments, R3is butyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one N(R4a’)C(O)O(R4b’). In some embodiments, each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl. 20 In some embodiments, R3is C1-C6alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one OC(O)N(R4a’)(R4b’). In some embodiments, each R4aand R4bis independently H or C1-C6alkyl. In some embodiments, R3is C1-C5alkyl that is substituted with one or more R3a, 25 wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one OC(O)N(R4a’)(R4b’). In some embodiments, each R4aand R4bis independently H or C1-C6alkyl. In some embodiments, R3is C1-C4 alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted 30 with one OC(O)N(R4a’)(R4b’). In some embodiments, each R4aand R4bis independently H or C1-C6alkyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is C1-C3alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one OC(O)N(R4a’)(R4b’). In some embodiments, each R4aand R4bis independently H or C1-C6alkyl. 5 In some embodiments, R3is C1-C2alkyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one OC(O)N(R4a’)(R4b’). In some embodiments, each R4aand R4bis independently H or C1-C6alkyl. In some embodiments, R3is methyl that is substituted with one or more R3a, wherein 10 each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one OC(O)N(R4a’)(R4b’). In some embodiments, each R4aand R4bis independently H or C1-C6alkyl. In some embodiments, R3is ethyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one 15 OC(O)N(R4a’)(R4b’). In some embodiments, each R4aand R4bis independently H or C1-C6alkyl. In some embodiments, R3is propyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one OC(O)N(R4a’)(R4b’). In some embodiments, each R4aand R4bis independently H or C1-C620 alkyl. In some embodiments, R3is , or . In some embodiments, R3is isopropyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one OC(O)N(R4a’)(R4b’). In some embodiments, each R4aand R4bis independently H or C1-C625 alkyl. In some embodiments, R3is butyl that is substituted with one or more R3a, wherein each R3ais independently 3- to 12-membered heterocyclyl that is optionally substituted with one OC(O)N(R4a’)(R4b’). In some embodiments, each R4aand R4bis independently H or C1-C6alkyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is C1-C6alkyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl that is substituted with one C1-C6alkyl and one N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H or C1-C6alkyl. 5 In some embodiments, R3is C1-C5alkyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl that is substituted with one C1-C6alkyl and one N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is C1-C4alkyl that is substituted with one or more R3a, 10 wherein R3ais 3- to 12-membered heterocyclyl that is substituted with one C1-C6alkyl and one N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is C1-C3alkyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl that is substituted with one C1-C6alkyl and one 15 N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is C1-C2alkyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl that is substituted with one C1-C6alkyl and one N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H or C1-C620 alkyl. In some embodiments, R3is methyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl that is substituted with one C1-C6 alkyl and one N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H or C1-C6alkyl. 25 In some embodiments, R3is ethyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl that is substituted with one C1-C6alkyl and one N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is propyl that is substituted with one or more R3a, wherein 30 R3ais 3- to 12-membered heterocyclyl that is substituted with one C1-C6alkyl and one N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H or C1-C6alkyl. In some embodiments, R3is . Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is isopropyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl that is substituted with one C1-C6alkyl and one N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H or C1-C6alkyl. 5 In some embodiments, R3is butyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl that is substituted with one C1-C6alkyl and one N(R4a’)C(O)(R4b’). In some embodiments, each R4a’ and R4b’ is independently H or C1-C6In some embodiments, R3is C1-C6alkyl that is substituted with one or more R3a, 10 wherein R3ais 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C5alkyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C4alkyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl. 15 In some embodiments, R3is C1-C3alkyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C2alkyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl. In some embodiments, R3is methyl that is substituted with one or more R3a, wherein 20 R3ais 3- to 12-membered heterocyclyl. In some embodiments, R3is ethyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl. In some embodiments, R3is propyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl. 25 In some embodiments, R3is C1-alkyl further substituted with an 8- to 11-membered spirocycle with 0-3 heteroatoms selected from N, O, and S. In some embodiments, R3is C2-alkyl further substituted with an 8- to 11-membered spirocycle with 0-3 heteroatoms selected from N, O, and S. In some embodiments, R3is C3-alkyl further substituted with an 8- to 11-membered 30 spirocycle with 0-3 heteroatoms selected from N, O, and S. In some embodiments, R3is C1-alkyl further substituted with an 8- to 9-membered spirocycle with 0-2 heteroatoms selected from N, O, and S. In some embodiments, R3is C2-alkyl further substituted with an 8- to 9-membered spirocycle with 0-2 heteroatoms selected from N, O, and S. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is C3-alkyl further substituted with an 8- to 9-membered spirocycle with 0-2 heteroatoms selected from N, O, and S. In some embodiments, R3is C1-alkyl further substituted with an 8- to 9-membered spirocycle with 1-2 heteroatoms selected from N, O, and S. 5 In some embodiments, R3is C2-alkyl further substituted with an 8- to 9-membered spirocycle with 1-2 heteroatoms selected from N, O, and S. In some embodiments, R3is C3-alkyl further substituted with an 8- to 9-membered spirocycle with 1-2 heteroatoms selected from N, O, and S. In some embodiments, R3is C1-alkyl further substituted with an 8- to 11-membered 10 spirocycle with 0-3 heteroatoms selected from N, O, and S, wherein the ring-forming members include CH, CH2, C(O), N, NH, O, S, S(O), and S(=O)2. In some embodiments, R3is C2-alkyl further substituted with an 8- to 11-membered spirocycle with 0-3 heteroatoms selected from N, O, and S, wherein the ring-forming members include CH, CH2, C(O), N, NH, O, S, S(O), and S(=O)2. 15 In some embodiments, R3is C3-alkyl further substituted with an 8- to 11-membered spirocycle with 0-3 heteroatoms selected from N, O, and S, wherein the ring-forming members include CH, CH2, C(O), N, NH, O, S, S(O), and S(=O)2. In some embodiments, R3is C1-alkyl further substituted with an 8- to 9-membered spirocycle with 0-2 heteroatoms selected from N, O, and S, wherein the ring-forming members 20 include CH, CH2, C(O), N, NH, O, S, S(O), and S(=O)2. In some embodiments, R3is C2-alkyl further substituted with an 8- to 9-membered spirocycle with 0-2 heteroatoms selected from N, O, and S, wherein the ring-forming members include CH, CH2, C(O), N, NH, O, S, S(O), and S(=O)2. In some embodiments, R3is C3-alkyl further substituted with an 8- to 9-membered 25 spirocycle with 0-2 heteroatoms selected from N, O, and S, wherein the ring-forming members include CH, CH2, C(O), N, NH, O, S, S(O), and S(=O)2. In some embodiments, R3is C1-alkyl further substituted with an 8- to 9-membered spirocycle with 1-2 heteroatoms selected from N, O, and S, wherein the ring-forming members include CH, CH2, C(O), N, NH, O, S, S(O), and S(=O)2. 30 In some embodiments, R3is C2-alkyl further substituted with an 8- to 9-membered spirocycle with 1-2 heteroatoms selected from N, O, and S, wherein the ring-forming members include CH, CH2, C(O), N, NH, O, S, S(O), and S(=O)2. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is C3-alkyl further substituted with an 8- to 9-membered spirocycle with 1-2 heteroatoms selected from N, O, and S, wherein the ring-forming members 5 In some embodiments, R3is isopropyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl. 10 In some embodiments, R3is butyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl. In some embodiments, R3is C1-C6 alkyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl that is substituted with 3- to 12-membered heterocyclyl that is substituted with oxo. 15 In some embodiments, R3is C1-C5alkyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl that is substituted with 3- to 12-membered heterocyclyl that is substituted with oxo. In some embodiments, R3is C1-C4alkyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl that is substituted with 3- to 12-membered 20 heterocyclyl that is substituted with oxo. In some embodiments, R3is C1-C3alkyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl that is substituted with 3- to 12-membered heterocyclyl that is substituted with oxo. In some embodiments, R3is C1-C2alkyl that is substituted with one or more R3a, 25 wherein R3ais 3- to 12-membered heterocyclyl that is substituted with 3- to 12-membered heterocyclyl that is substituted with oxo. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, R3is methyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl that is substituted with 3- to 12-membered heterocyclyl that is substituted with oxo. In some embodiments, R3is ethyl that is substituted with one or more R3a, wherein R3a5 is 3- to 12-membered heterocyclyl that is substituted with 3- to 12-membered heterocyclyl that is substituted with oxo. In some embodiments, R3is propyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl that is substituted with 3- to 12-membered heterocyclyl that is substituted with oxo. In some embodiments, R3is . 10 In some embodiments, R3is isopropyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl that is substituted with 3- to 12-membered heterocyclyl that is substituted with oxo. In some embodiments, R3is butyl that is substituted with one or more R3a, wherein R3ais 3- to 12-membered heterocyclyl that is substituted with 3- to 12-membered heterocyclyl that 15 is substituted with oxo. In some embodiments, 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-C6alkyl, C3-C12cycloalkyl, C1-C6alkoxy, C6-C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein the C1-C6alkyl, C3-C12cycloalkyl, C6-C10aryl, 3- to 12-membered 20 heterocyclyl or 5- to 10-membered heteroaryl is optionally substituted with one or more C1-C6alkyl that is optionally substituted with O(R4a). In some embodiments, 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-C6alkyl, C3-C12cycloalkyl, C1-C6alkoxy, C6-C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered 25 heteroaryl, wherein the C1-C6 alkyl, C3-C12 cycloalkyl, C6-C10 aryl, 3- to 12-membered heterocyclyl or 5- to 10-membered heteroaryl is optionally substituted with one or more 3- to 12-membered heterocyclyl that is optionally substituted with oxo. In some embodiments, R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 12-membered 30 heterocyclyl 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), C1-C6alkyl, C3-C12cycloalkyl, C1-C6alkoxy, C6- Attorney Docket No. SYND-060 / 001WO 327830-2818 C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein the C1-C6alkyl, C3-C12cycloalkyl, C6-C10aryl, 3- to 12-membered heterocyclyl 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’), 5 N(R4a’)C(O)O(R4b’), C1-C6alkyl that is optionally substituted with O(R4a), and 3- to 12- membered heterocyclyl that is optionally substituted with oxo; and each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl. In some embodiments, R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen atom to which it is connected. 10 , , 15 In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, W is N, Y is N, R1is methyl, R2is isopropyl, and Z is O. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, and Z is O. 20 In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, and Z is O. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, and Z is O. In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, and Z is O. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, and Z is O. In some embodiments, W is N, Y is CH, R1is isopropyl, R2is isopropyl, and Z is O. 5 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, and Z is O. In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, and Z is O. In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, and Z is O. In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, 10 and Z is O. In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, and Z is O. In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, and Z is O. 15 In some embodiments, W is CH, Y is CH, R1is -CH2-phenyl, R2is isopropyl, and Z is In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, and Z is O. In some embodiments, W is N, Y is CH, R1is -CH=CHF, R2is isopropyl, and Z is O. In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, and Z is O. 20 In some embodiments, W is CH, Y is CH, R1is -CH=CHF, R2is isopropyl, and Z is O. In some embodiments, isopropyl, and Z is O. 25 In some embodiments, W is N, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, and Z is O. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, and Z is O. In some embodiments, and Z is O. 5 isopropyl, and Z is O. In some embodiments, W is N, Y is N, R1and R2form a group selected from: In some embodiments, W is CH, Y is N, R1and R2form a group selected from: 10 In some embodiments, W is CH, Y is N, and Z is CH2. In some embodiments, W is CH, Y is N, R1is ethyl, and Z is CH2. In some embodiments, W is CH, Y is N, R1is isopropyl, and Z is CH2. In some embodiments, W is CH, Y is N, R2is isopropyl, and Z is CH2. 15 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, and Z is CH2. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, and Z is CH2. In some embodiments, W is CH, Y is N, and Z is NH. In some embodiments, W is CH, Y is N, R1is ethyl, and Z is NH. In some embodiments, W is CH, Y is N, R1is isopropyl, and Z is NH. 20 In some embodiments, W is CH, Y is N, R2is isopropyl, and Z is NH. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, and Z is NH. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, and Z is NH. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, and Ring A is . 5 In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, and Ring A is . In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, and Ring A is . In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, and Ring A is 10 . In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, and Ring A is . In some embodiments, W is N, Y is CH, R1is isopropyl, R2is isopropyl, and Ring A is . 15 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, and Ring A is . In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, and Ring A W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, 20 In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, and Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, and Ring In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, and Ring 5 In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, and Ring A is . In some embodiments, W is N, Y is CH, R1is -CH=CHF, R2is isopropyl, and Ring A In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, and Ring A 10 In some embodiments, W is CH, Y is CH, R1is -CH=CHF, R2is isopropyl, and Ring In some embodiments, W is N, Y is N, R1and R2form a group selected from: 15 In some embodiments, W is CH, Y is N, R1and R2form a group selected from: In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, and Ring A In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, Z is O, and Ring 20 Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, and Ring In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, Z is O, and Ring 5 In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Z is O, and Ring In some embodiments, W is N, Y is CH, R1is isopropyl, R2is isopropyl, Z is O, and Ring In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is O, and 10 Ring In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, Z is O, and In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, and Ring 15 In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, and Ring In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, and Ring In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is 20 isopropyl, Z is O, and Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, and Ring In some embodiments, W is N, Y is CH, R1is -CH=CHF, R2is isopropyl, Z is O, and Ring 5 In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, and Ring In some embodiments, W is CH, Y is CH, R1is -CH=CHF, R2is isopropyl, Z is O, and Ring In some embodiments, W is N, Y is N, R1and R2form a group selected from: 10 In some embodiments, W is CH, Y is N, R1and R2form a group selected from: In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is NH, and Ring 15 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is NH, and Ring In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, and Ring A is . In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, and Ring A is 20 . Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, and Ring A is . In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, and Ring A is . 5 In some embodiments, W is N, Y is N, R1is methyl, R2is isopropyl, and Ring A is . In some embodiments, W is CH, Y is N, R1is -CH2-phenyl, R2is isopropyl, and Ring In some embodiments, W is N, Y is N, R1is -CH2-phenyl, R2is isopropyl, and Ring A 10 In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, and Ring A is . In some embodiments, W is N, Y is CH, R1is isopropyl. R2is isopropyl, and Ring A is . 15 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, and Ring A is . In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, and Ring A 20 Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, and Ring In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, and Ring 5 In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, and Ring In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, and Ring A is . In some embodiments, W is N, Y is CH, R1is -CH=CHF, R2is isopropyl, and Ring A 10 In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, and Ring A In some embodiments, W is CH, Y is CH, R1is -CH=CHF, R2is isopropyl, and Ring 15 Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, isopropyl, and Ring In some embodiments, W is N, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, and Ring 5 In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, and Ring In some embodiments, W is CH, Y is N, R1is -CH2-CN, R2is isopropyl, and Ring A is . In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one OH and 10 one methyl group, R2is isopropyl, and Ring A is . In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one CN and one methyl group, R2is isopropyl, and Ring A is . In some embodiments, W is N, Y is N, R1is cyclobutyl substituted by one methoxy group, R2is isopropyl, and Ring A is . 15 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H-pyrazol- 1-yl group, R2is isopropyl, and Ring A is . In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group, and Ring In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- 20 imidazol-1-yl group and one methyl group, and Ring A is . Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, In some embodiments, 5 a group selected from: selected from: In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, and Ring A 10 In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, Z is O, and Ring In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, and Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, Z is O, and Ring In some embodiments, W is N, Y is N, R1is methyl, R2is isopropyl, Z is O, and Ring 5 W is CH, Y is N, R1is -CH2-phenyl, R2is isopropyl, Z is O, and In some embodiments, W is N, Y is N, R1is -CH2-phenyl, R2is isopropyl, Z is O, and W is N, Y is N, R1is isopropyl, R2is isopropyl, Z is O, and Ring 10 In some embodiments, W is N, Y is CH, R1is isopropyl, R2is isopropyl, Z is O, and Ring In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is O, and Ring 15 In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, Z is O, and In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is 20 isopropyl, Z is O, and Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, and Ring In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, and Ring 5 In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, and Ring In some embodiments, W is N, Y is CH, R1is -CH=CHF, R2is isopropyl, Z is O, and Ring In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, and 10 Ring In some embodiments, W is CH, Y is CH, R1is -CH=CHF, R2is isopropyl, Z is O, and Ring In some embodiments, W is CH, Y is N, R1is , , 15 and Ring In some embodiments, W is N, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Z is O, and Ring In some embodiments, W is CH, Y is N, R1is -CH2-CN, R2is isopropyl, Z is O, and Ring 5 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one OH and one methyl group, R2is isopropyl, Z is O, and Ring A is . In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one CN and one methyl group, R2is isopropyl, Z is O, and Ring A is . In some embodiments, W is N, Y is N, R1is cyclobutyl substituted by one methoxy 10 group, R2is isopropyl, Z is O, and Ring A is . In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H-pyrazol- 1-yl group, R2is isopropyl, Z is O, and Ring A is . In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group, Z is O, and Ring 15 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group and one methyl group, Z is O, and Ring A is . In some embodiments, Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1and R2form a group selected from: 5 In some embodiments, W is CH, Y is N, R1and R2form a group selected from: In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is CH2, and Ring In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is CH2, and Ring 10 W is N, Y is N, R1is isopropyl, R2is isopropyl, Z is CH2, and In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is CH2, and 15 W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is NH, and Ring In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is NH, and Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, and Ring In some embodiments, W is CH, Y is N, R1is ethyl, and Ring . In some embodiments, W is CH, Y is N, R1is isopropyl, and Ring 5 . In some embodiments, W is CH, Y is N, R2is isopropyl, and Ring W is CH, Y is N, R1is ethyl, R2is isopropyl, and Ring A is 10 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, and Ring A is In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is O, and Ring In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, and Z is O, and X315 is H. In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, and Z is O, and X3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, and Z is O, and X3is H. In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, and Z is O, and X3is H. 5 In some embodiments, W is N, Y is N, R1is -CH2-phenyl, R2is isopropyl, and Z is O, and X3is H. In some embodiments, W is CH, Y is N, R1is -CH2-CN, R2is isopropyl, and Z is O, and X3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one OH and 10 one methyl group, R2is isopropyl, and Z is O, and X3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one CN and one methyl group, R2is isopropyl, and Z is O, and X3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one methoxy group, R2is isopropyl, and Z is O, and X3is H. 15 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H-pyrazol- 1-yl group, R2is isopropyl, and Z is O, and X3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group, R2is isopropyl, and Z is O, and X3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- 20 imidazol-1-yl group and one methyl group, R2is isopropyl, and Z is O, and X3is H. In some embodiments, W is N, Y is N, R1is methyl, R2is isopropyl, Z is O, and X3is H. In some embodiments, W is N, Y is N, R1is methyl, R2is isopropyl, Z is O, X3is H, 25 . Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, and Z is O, and X3is H. In some embodiments, W is N, Y is CH, R1is isopropyl, R2is isopropyl, and Z is O, 5 and X3is H. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, and Z is O, and X3is H. In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, and Z is O, and X3is H. 10 In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, and Z is O, and X3is H. In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, and Z is O, and X3is H. In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, 15 and Z is O, and X3is H. In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, and Z is O, and X3is H. In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, and Z is O, and X3is H. 20 In some embodiments, W is N, Y is CH, R1is -CH=CHF, R2is isopropyl, and Z is O, and X3is H. In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, and Z is O, and X3is H. In some embodiments, W is CH, Y is CH, R1is -CH=CHF, R2is isopropyl, and Z is O, 25 and X3is H. In some embodiments, W is CH, Y is N, R1is , , isopropyl,3 and Z is O, and X is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, isopropyl, and Z is O, and X3is H. In some embodiments, W is N, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, 5 and Z is O, and X3is H. In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, and Z is O, and X3is H. 10 isopropyl, and Z is O, a3 nd X is H. In some embodiments, W is N, Y is N, R1and R2form a group selected from: In some embodiments, W is CH, Y is N, R1and R2form a group selected from: 15 In some embodiments, W is CH, Y is N, Z is CH2, and X3is H. In some embodiments, W is CH, Y is N, R1is ethyl, Z is CH2, and X3is H. In some embodiments, W is CH, Y is N, R1is isopropyl, Z is CH2, and X3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R2is isopropyl, Z is CH2, and X3is H. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, and Z is CH2, and X3is H. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is CH2, and 5 X3is H. In some embodiments, W is CH, Y is N, Z is NH, and X3is H. In some embodiments, W is CH, Y is N, R1is ethyl, Z is NH, and X3is H. In some embodiments, W is CH, Y is N, R1is isopropyl, Z is NH, and X3is H. In some embodiments, W is CH, Y is N, R2is isopropyl, Z is NH, and X3is H. 10 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is NH, and X3is H. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is NH, and X3is H. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Ring A is 15 , and X3is H. In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, Ring A is , and X3is H. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Ring A is , and X3is H. 20 In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, Ring A is W is N, Y is N, R1is isopropyl, R2is isopropyl, Ring A is W is N, Y is CH, R1is isopropyl, R2is isopropyl, Ring A is 25 Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Ring A is W is CH, Y is CH, R1is isopropyl, R2is isopropyl, Ring A is 5 In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Ring In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Ring In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, 10 Ring In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, Ring A is 15 W is N, Y is CH, R1is -CH=CHF, R2is isopropyl, Ring A is W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, Ring A is In some embodiments, W is CH, Y is CH, R1is -CH=CHF, R2is isopropyl, Ring A is 20 In some embodiments, W is N, Y is N, R1and R2form a group selected from: Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1and R2form a group selected from: In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is 5 W is N, Y is CH, R1is ethyl, R2is isopropyl, Z is O, Ring A is W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is 10 In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, Z is O, Ring A W is N, Y is N, R1is isopropyl, R2is isopropyl, Z is O, Ring A In some embodiments, W is N, Y is CH, R1is isopropyl, R2is isopropyl, Z is O, Ring 15 In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, Z is O, Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring 5 In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, Ring 10 In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, Ring 15 In some embodiments, W is N, Y is N, R1and R2form a group selected from: In some embodiments, W is CH, Y is N, R1and R2form a group selected from: 20 Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is NH, Ring A 5 In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Ring A is , and X3is H. In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, Ring A is , and X3is H. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Ring A is 10 , and X3is H. In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, Ring A is , and X3is H. In some embodiments, W is N, Y is N, R1is methyl, R2is isopropyl, Ring A is , and X3is H. 15 In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Ring A is , and X3is H. In some embodiments, W is N, Y is CH, R1is isopropyl, R2is isopropyl, Ring A is , and X3is H. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Ring A is 20 , and X3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, Ring A is , and X3is H. In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2,R2is isopropyl, Ring 5 In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Ring In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Ring In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is 10 isopropyl, Ring In some embodiments, W is N, Y is N, R1is -CH2-phenyl, R2is isopropyl, Ring A is , and X3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one methoxy group, R2is isopropyl, Ring A is , and X3is H. 15 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H-pyrazol- 1-yl group, R2is isopropyl, Ring A is , and X3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group, R2is isopropyl, Ring A is , and X3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- 20 imidazol-1-yl group and one methyl group, R2is isopropyl, Ring A is , and X3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, Ring A is , and X3is H. In some embodiments, W is N, Y is CH, R1is -CH=CHF, R2is isopropyl, Ring A is , and X3is H. 5 In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, Ring A is , and X3is H. In some embodiments, W is CH, Y is CH, R1is -CH=CHF, R2is isopropyl, Ring A is 10 In some embodiments, W is N, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, 15 Ring In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, , or In , , or 5 In some embodiments, W is N, Y is N, R1and R2form a group selected from: In some embodiments, W is CH, Y is N, R1and R2form a group selected from: In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is 10 , and X3is H. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , and X3is -CH2-O-CH2-CHF2. In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, Z is O, Ring A is , and X3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is 5 In some embodiments, W is N, Y is N, R1is methyl, R2is isopropyl, Z is O, Ring A is In some embodiments, W is N, Y is CH, R1is isopropyl, R2is isopropyl, Z is O, Ring 10 In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, Z is O, Ring 15 In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is 20 isopropyl, Z is O, Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring In some embodiments, W is N, Y is N, R1is -CH2-phenyl, R2is isopropyl, Z is O, Ring 5 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one OH and one methyl group, R2is isopropyl, Z is O, Ring A is , and X3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one CN and 10 one methyl group, R2is isopropyl, Z is O, Ring A is , and X3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one methoxy group, R2is isopropyl, Z is O, Ring A is , and X3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H-pyrazol- 15 substituted by one 1H- imidazol-1-yl group, R2is isopropyl, Z is O, Ring A is , and X3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group and one methyl group, R2is isopropyl, Z is O, Ring A is X3is H. 20 In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is CH, R1is -CH=CHF, R2is isopropyl, Z is O, Ring 5 In some embodiments, W is CH, Y is CH, R1is -CH=CHF, R2is isopropyl, Z is O, In some embodiments, isopropyl, Z is O, 10 Ring In some embodiments, W is N, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Z is O, Ring In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Z is O, Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, In some embodiments, 5 In some embodiments, W is N, Y is N, R1and R2form a group selected from: In some embodiments, W is CH, Y is N, R1and R2form a group selected from: In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is CH2, Ring A is 10 In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Z is CH2, Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is CH2, Ring In some embodiments, W is CH, Y is N, Z is NH, Ring A is , and X3is H. In some embodiments, W is CH, Y is N, R1is ethyl, Z is NH, Ring A is , and 5 X3is H. In some embodiments, W is CH, Y is N, R1is isopropyl, Z is NH, Ring A is , and X3is H. In some embodiments, W is CH, Y is N, R2is isopropyl, Z is NH, Ring A is , and X3is H. 10 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is NH, Ring A In some embodiments, W is CH, Y is N, Ring 15 H. In some embodiments, W is CH, Y is N, R1is ethyl, Ring , and X3is H. In some embodiments, W is CH, Y is N, R1is isopropyl, Ring A is , and X3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R2is isopropyl, Ring , and X3is H. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Ring A is 5 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is 10 In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, and X3is methyl, ethyl, or isopropyl. 15 In some embodiments, isopropyl,3 and X is hydrogen. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, and X3is methyl, ethyl, or isopropyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, and X3is methyl, ethyl, or isopropyl. 5 In some embodiments, W is N, Y is CH, R1is isopropyl, R2is isopropyl, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, and X3is 10 methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, and X3is methyl, ethyl, or isopropyl. 15 In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, and X3is 20 methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is CH, R1is -CH=CHF, R2is isopropyl, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, and X3is methyl, ethyl, or isopropyl. 25 In some embodiments, W is CH, Y is CH, R1is -CH=CHF, R2is isopropyl, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is CH, R1is cyclopropyl or cyclobutyl, R2is 30 isopropyl, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl and R2is isopropyl, and X3is methyl, ethyl, or isopropyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, and X3is methyl, ethyl, or isopropyl. isopropyl, and X3is methyl, ethyl, or isopropyl. 5 In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, and X3is - CH2-O-CH2-CHF2. In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, Z is O, and X3is 10 methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, Z is O, and X3is methyl, ethyl, or isopropyl. 15 In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Z is O, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is CH, R1is isopropyl, R2is isopropyl, Z is O, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is O, and 20 X3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, Z is O, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, and X3is methyl, ethyl, or isopropyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, and X3is methyl, ethyl, or isopropyl. 5 In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, 10 Z is O, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Z is O, and X3is methyl, ethyl, or isopropyl. In some embodiments, isopropyl, Z is O, and X3is methyl, ethyl, or isopropyl. 15 isopropyl, Z is O, and X3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Ring A is , and X3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Ring A is 20 , and X3is methyl, ethyl, or isopropyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Ring A is , and X3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Ring A is , and X3is methyl, ethyl, or isopropyl. 5 In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2,R2is isopropyl, Ring A is , and X3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Ring A is , and X3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, Ring A is 10 , and X3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, Ring A is , and X3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Ring A is , and X3is methyl, ethyl, or isopropyl. 15 In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Ring A is , and X3is methyl, ethyl, or isopropyl. In some embodiments, , methyl, ethyl, or isopropyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, , and X3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , and X3is methyl, ethyl, or isopropyl. 5 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , and X3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Z is O, Ring A is , and X3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is O, Ring 10 A is , and X3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring A is , and X3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring A is , and X3is methyl, ethyl, or isopropyl. 15 In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, Ring A is , and X3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, Ring A is , and X3is methyl, ethyl, or isopropyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Z is O, Ring A is , and X3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Z is O, Ring A is , and X3is methyl, ethyl, or isopropyl. 5 In some embodiments, , and X3is methyl, ethyl, or isopropyl. In some embodiments, , and X3is methyl, ethyl, or 10 isopropyl. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, and X3is - CH2(OH), -CH2-CH2-CH2(OH), -CH2-OCH3, -CH2-CH2-CH2-O-CH2-phenyl, -CH2-CH2-CH2- C(=O)N(CH3)2, or -CH2-CH2-CH2-N(CH3)2. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, and X3is -15 CH2(OH), -CH2-CH2-CH2(OH), -CH2-OCH3, -CH2-CH2-CH2-O-CH2-phenyl, -CH2-CH2-CH2- C(=O)N(CH3)2, or -CH2-CH2-CH2-N(CH3)2. In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl and R2is isopropyl, and X3is -CH2(OH), -CH2-CH2-CH2(OH), -CH2-OCH3, -CH2-CH2-CH2-O-CH2- phenyl, -CH2-CH2-CH2-C(=O)N(CH3)2, or -CH2-CH2-CH2-N(CH3)2. Attorney Docket No. SYND-060 / 001WO 327830-2818 CH2-CH2-CH2-O-CH2-phenyl, -CH2-CH2-CH2-C(=O)N(CH3)2, or -CH2-CH2-CH2-N(CH3)2. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, and X3is - 5 CH2(OH), -CH2-CH2-CH2(OH), -CH2-OCH3, -CH2-CH2-CH2-O-CH2-phenyl, -CH2-CH2-CH2- C(=O)N(CH3)2, or -CH2-CH2-CH2-N(CH3)2. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is O, and X3is -CH2(OH), -CH2-CH2-CH2(OH), -CH2-OCH3, -CH2-CH2-CH2-O-CH2-phenyl, -CH2- CH2-CH2-C(=O)N(CH3)2, or -CH2-CH2-CH2-N(CH3)2. 10 In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Z is O, and X3is -CH2(OH), -CH2-CH2-CH2(OH), -CH2-OCH3, -CH2-CH2-CH2-O- 15 OCH3, -CH2-CH2-CH2-O-CH2-phenyl, -CH2-CH2-CH2-C(=O)N(CH3)2, or -CH2-CH2-CH2- N(CH3)2. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Ring A is , and X3is -CH2(OH), -CH2-CH2-CH2(OH), -CH2-OCH3, -CH2-CH2-CH2-O-CH2- phenyl, -CH2-CH2-CH2-C(=O)N(CH3)2, or -CH2-CH2-CH2-N(CH3)2. 20 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Ring A is , and X3is -CH2(OH), -CH2-CH2-CH2(OH), -CH2-OCH3, -CH2-CH2-CH2-O-CH2- phenyl, -CH2-CH2-CH2-C(=O)N(CH3)2, or -CH2-CH2-CH2-N(CH3)2. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Ring A is , and X3is -CH2(OH), -CH2-CH2-CH2(OH), -CH2-OCH3, -CH2- CH2-CH2-O-CH2-phenyl, - In some embodiments, 5 CH2(OH), -CH2-OCH3, -CH2-CH2-CH2-O-CH2-phenyl, -CH2-CH2-CH2-C(=O)N(CH3)2, or - CH2-CH2-CH2-N(CH3)2. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , and X3is -CH2(OH), -CH2-CH2-CH2(OH), -CH2-OCH3, -CH2-CH2-CH2-O-CH2- 10 phenyl, -CH2-CH2-CH2-C(=O)N(CH3)2, or -CH2-CH2-CH2-N(CH3)2. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is O, Ring A is , and X3is -CH2(OH), -CH2-CH2-CH2(OH), -CH2-OCH3, -CH2-CH2-CH2-O- CH2-phenyl, -CH2-CH2-CH2-C(=O)N(CH3)2, or -CH2-CH2-CH2-N(CH3)2. In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl, R2is 15 isopropyl, Z is O, Ring A is , and X3is -CH2(OH), -CH2-CH2-CH2(OH), -CH2- OCH3, -CH2-CH2-CH2-O-CH2-phenyl, -CH2-CH2-CH2-C(=O)N(CH3)2, or -CH2-CH2-CH2- N(CH3)2. In some embodiments, Attorney Docket No. SYND-060 / 001WO 327830-2818 CH2(OH), -CH2-OCH3, -CH2-CH2-CH2-O-CH2-phenyl, -CH2-CH2-CH2-C(=O)N(CH3)2, or - CH2-CH2-CH2-N(CH3)2. In any one of the proceeding embodiments, R3is selected from one or more of the following: 5 a. H; b. methyl, ethyl, or isopropyl; 10 h. -CH2-C(O)OH, -CH2-CH2-C(O)OH, or -CH2-CH2-OMe; i. -CH2-CH2-CN; j. -CH2-CH2-S(=O)2Me or -CH2-CH2-CH2-S(=O)2Me; 15 k. -CH2-CH2-NH(CH3), -CH2-CH2-CH2-NH(CH3), or -CH2-CH2-CH2-CH2- NH(CH3); or -CH2-CH2-CH2-CH2-CH2-NH(CH3); l. -CH2-CH2-N(CH3)2, -CH2-CH2-CH2-N(CH3)2, -CH2-CH2-CH2-CH2-N(CH3)2, or -CH2-CH2-CH2-CH2-CH2-N(CH3)2; m. -CH2-CH2-CH2-N(CH2-CH3)2; 20 n. -CH2-CH2-NH2, -CH2-CH2-CH2-NH2, or -CH2-CH2-C(CH3)2(NH2); o. -CH2-CH2-OH, -CH2-CH2-CH2-OH, -CH2-CH2-C(CH3)2(OH), -CH2- C(CH3)2(OH), -CH2-C(CH3)2(OH), or -CH2-CH2-C(CH3)2(OH); p. -CH2-C(O)OH; or -CH2-CH2-C(O)OH; q. Attorney Docket No. SYND-060 / 001WO 327830-2818 510 15 Attorney Docket No. SYND-060 / 001WO 327830-2818 5 10 Attorney Docket No. SYND-060 / 001WO 327830-2818 , , , , 5 10 Attorney Docket No. SYND-060 / 001WO 327830-2818 5 10 Attorney Docket No. SYND-060 / 001WO 327830-2818 5 10 Attorney Docket No. SYND-060 / 001WO 327830-2818 5 In any one of the previous embodiments, wherein n is 1. In any one of the previous embodiments, wherein n is 2. In any one of the previous embodiments, wherein n is 3. 10 In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, and R3is H. In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, and R3is H. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, and R3is H. In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, and R3is H. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, and R3is H. 15 In some embodiments, W is N, Y is CH, R1is isopropyl, R2is isopropyl, and R3is H. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, and R3is H. In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, and R3is In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, 20 and R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, and R3is H. In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, and R3is H. 5 In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, and R3is H. In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, and R3is H. In some embodiments, W is N, Y is CH, R1is -CH=CHF, R2is isopropyl, and R3is H. In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, and R3is H. 10 In some embodiments, W is CH, Y is CH, R1is -CH=CHF, R2is isopropyl, and R3is In some embodiments, isopropyl3 , and R 15 is H. In some embodiments, W is N, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, and R3is H. In some embodiments, W is N, Y is CH, R1is cyclopropyl or cyclobutyl, R2is isopropyl, and R3is H. 20 In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl and R2is isopropyl, and R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, isopropyl3 , and R is H. In some embodiments, , , or , R2is isopropyl, and R3is H. 5 In some embodiments, W is N, Y is N, R1and R2form a group selected from: In some embodiments, W is CH, Y is N, R1and R2form a group selected from: In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, and R3is H. 10 In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, Z is O, and R3is H. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, and R3is H. In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, Z is O, and R3is 15 H. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Z is O, and R3is H. In some embodiments, W is N, Y is CH, R1is isopropyl, R2is isopropyl, Z is O, and R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is O, and R3is H. In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, Z is O, and R3is H. 5 In some embodiments, W is N, Y is N, R1is -CH2-phenyl, R2is isopropyl, Z is O, and R3is H. In some embodiments, W is CH, Y is N, R1is -CH2-CN, R2is isopropyl, Z is O, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one OH and 10 one methyl group, R2is isopropyl, Z is O, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one CN and one methyl group, R2is isopropyl, Z is O, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one methoxy group, R2is isopropyl, Z is O, and R3is H. 15 In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, and R3is H. In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, and R3is H. In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, 20 Z is O, and R3is H. In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, and R3is H. In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, and R3is H. 25 In some embodiments, W is N, Y is CH, R1is -CH=CHF, R2is isopropyl, Z is O, and R3is H. In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, and R3is H. In some embodiments, W is CH, Y is CH, R1is -CH=CHF, R2is isopropyl, Z is O, and 30 R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is , , isopropyl, Z is3 O, and R is H. In some embodiments, isopropyl, Z is O, and R3is H. 5 In some embodiments, W is N, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Z is O, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Z is O, and R3is H. In some embodiments, 10 Z is O, and R3is H. isopropyl, Z is O, and R3 is H. In some embodiments, W is N, Y is N, R1and R2form a group selected from: 15 In some embodiments, W is CH, Y is N, R1and R2form a group selected from: Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is CH2, and R3is H. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is CH2, and 5 R3is H. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is NH, and R3is H. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is NH, and R3is H. 10 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H-pyrazol- 1-yl group, R2is isopropyl, Z is O, and R3is -CH3. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group, R2is isopropyl, Z is O, and R3is -CH3. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- 15 imidazol-1-yl group and one methyl group, R2is isopropyl, Z is O, and R3is -CH3. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Ring A is , and R3is H. In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, Ring A is , and R3is H. 20 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Ring A is , and R3is H. In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, Ring A is W is N, Y is N, R1is isopropyl, R2is isopropyl, Ring A is 25 Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is CH, R1is isopropyl, R2is isopropyl, Ring A is W is CH, Y is N, R1is isopropyl, R2is isopropyl, Ring A is 5 W is CH, Y is CH, R1is isopropyl, R2is isopropyl, Ring A is In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, 10 In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Ring 15 In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Ring CH2-N(CH3)2, or -CH2-CH2-CH2-CH2-CH2-N(CH3)2. In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, Ring A is 20 W is N, Y is CH, R1is -CH=CHF, R2is isopropyl, Ring A is Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, Ring A is W is CH, Y is CH, R1is -CH=CHF, R2is isopropyl, Ring A is 5 In some embodiments, W is N, Y is N, R1and R2form a group selected from: from: In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is 10 W is N, Y is CH, R1is ethyl, R2is isopropyl, Z is O, Ring A is W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is 15 In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, Z is O, Ring A W is N, Y is N, R1is isopropyl, R2is isopropyl, Z is O, Ring A In some embodiments, W is N, Y is CH, R1is isopropyl, R2is isopropyl, Z is O, Ring 20 Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is O, Ring 5 In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is 10 isopropyl, Z is O, Ring In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, Ring 15 In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, Ring 20 In some embodiments, W is N, Y is N, R1and R2form a group selected from: Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1and R2form a group selected from: In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is NH, Ring A 5 In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Ring A is , and R3is H. 10 In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, Ring A is , and R3is H. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Ring A is , and R3is H. In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, Ring A is 15 , and R3is H. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Ring A is , and R3is H. In some embodiments, W is N, Y is CH, R1is isopropyl, and R3is H. R2is isopropyl, Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Ring A is , and R3is H. In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, Ring A is , and R3is H. 5 In some embodiments, W is N, Y is N, R1is -CH2-phenyl, R2is isopropyl, Ring A is , and R3is H. some embodiments, W is CH, Y is N, R1is -CH2-CN, R2is isopropyl, Ring A is , and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one OH and 10 one methyl group, R2is isopropyl, Ring A is , and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one CN and one methyl group, R2is isopropyl, Ring A is , and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one methoxy group, R2is isopropyl, Ring A is , and R3is H. 15 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H-pyrazol- 1-yl group, R2is isopropyl, Ring A is , and R3is -CH3. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group, R2is isopropyl, Ring A is , and R3is -CH3. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- 20 imidazol-1-yl group and one methyl group, R2is isopropyl, Ring A is , and R3is - CH3. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1is -CH2-phenyl, R2is isopropyl, Z is O, Ring 5 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one OH and one methyl group, R2is isopropyl, Z is O, Ring A is , and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one CN and one methyl group, R2is isopropyl, Z is O, Ring A is , and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one methoxy 10 group, R2is isopropyl, Z is O, Ring A is , and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H-pyrazol- by one 1H- imidazol-1-yl group, R2is isopropyl, Z is O, Ring A is , and R3is -CH3. 15 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group and one methyl group, R2is isopropyl, Z is O, Ring A is R3is -CH3. In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2,R2is isopropyl, Ring 20 In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Ring A is , and R3is H. In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Ring A is , and R3is -CH2-CH2-N(CH3)2, -CH2-CH2-CH2-N(CH3)2, -CH2-CH2-CH2- 5 CH2-N(CH3)2, or -CH2-CH2-CH2-CH2-CH2-N(CH3)2. In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Ring A is , and R3is H. In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, Ring A is , and R3is H. 10 In some embodiments, W is N, Y is CH, R1is -CH=CHF, R2is isopropyl, Ring A is , and R3is H. In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, Ring A is , and R3is H. In some embodiments, W is CH, Y is CH, R1is -CH=CHF, R2is isopropyl, Ring A is 15 Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Ring 5 In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Ring In some embodiments, 10 In some embodiments, W is N, Y is N, R1and R2form a group selected from: In some embodiments, W is CH, Y is N, R1and R2form a group selected from: Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , and R3is H. In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, Z is O, Ring A is , and R3is H. 5 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Z is O, Ring A 10 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is O, Ring 15 In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is 20 isopropyl, Z is O, Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring 5 In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, Ring In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, Ring 10 In some embodiments, W is CH, Y is N, R1is , , 15 In some embodiments, Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Z is O, Ring In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Z is O, Ring 5 In some embodiments, In some embodiments, In some embodiments, W is N, Y is N, R1and R2form a group selected from: 10 In some embodiments, W is CH, Y is N, R1and R2form a group selected from: In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is CH2, Ring A is Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is CH2, Ring A is In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is CH2, Ring A 5 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is CH2, Ring 10 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is NH, Ring 15 In some embodiments, W is CH, Y is N, R1is ethyl, Ring , and R3is H. In some embodiments, W is CH, Y is N, R1is isopropyl, Ring , and R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R2is isopropyl, Ring 5 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Ring A is In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is O, Ring 10 In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, X3is H, and R3is H. In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, X3is H, and R3is H. 15 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, X3is H, and R3is H. In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, X3is H, and R3is H. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, X3is H, and R320 is H. In some embodiments, W is N, Y is CH, R1is isopropyl, R2is isopropyl, X3is H, and R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, X3is H, and R3is H. In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, X3is H, and R3is H. 5 In some embodiments, W is N, Y is N, R1is -CH2-phenyl, R2is isopropyl, X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is -CH2-CN, R2is isopropyl, X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one OH and 10 one methyl group, R2is isopropyl, X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one CN and one methyl group, R2is isopropyl, X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one methoxy group, R2is isopropyl, X3is H, and R3is H. 15 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H-pyrazol- 1-yl group, R2is isopropyl, X3is H, and R3is -CH3. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group, R2is isopropyl, X3is H, and R3is -CH3. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- 20 imidazol-1-yl group and one methyl group, R2is isopropyl, X3is H, and R3is -CH3. In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, X3is H, and R3is H. In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, X3is H, and R3is H. 25 In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, X3is H, and R3is H. In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, X3is H, and R3is H. In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, X3is H, and 30 R3is H. In some embodiments, W is N, Y is CH, R1is -CH=CHF, R2is isopropyl, X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, X3is H, and R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is CH, R1is -CH=CHF, R2is isopropyl, X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is , , isopropyl, X3is H, a3 nd R is H. 5 In some embodiments,3 isopropyl, X is H, and R3is H. In some embodiments, W is N, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, X3is H, and R3is H. In some embodiments, W is N, Y is CH, R1is cyclopropyl or cyclobutyl, R2is 10 isopropyl, X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl and R2is isopropyl, X3is H, and R3is H. In some embodiments, X3is H, and R3is H. 15 isopro3 3 pyl, X is H, and R is H. In some embodiments, W is N, Y is N, R1and R2form a group selected from: Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1and R2form a group selected from: In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, X3is H, and 5 R3is H. In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, Z is O, X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, X3is H, and R3is H. 10 In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, Z is O, X3is H, and R3is H. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Z is O, X3is H, and R3is H. In some embodiments, W is N, Y is CH, R1is isopropyl, R2is isopropyl, Z is O, X3is 15 H, and R3is H. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is O, X3is H, and R3is H. In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, Z is O, X3is H, and R3is H. 20 In some embodiments, W is N, Y is N, R1is -CH2-phenyl, R2is isopropyl, Z is O, X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is -CH2-CN, R2is isopropyl, Z is O, X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one OH and 25 one methyl group, R2is isopropyl, Z is O, X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one CN and one methyl group, R2is isopropyl, Z is O, X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one methoxy group, R2is isopropyl, Z is O, X3is H, and R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H-pyrazol- 1-yl group, R2is isopropyl, Z is O, X3is H, and R3is -CH3. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group, R2is isopropyl, Z is O, X3is H, and R3is -CH3. 5 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group and one methyl group, R2is isopropyl, Z is O, X3is H, and R3is -CH3. In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, X3is H, and R3is H. In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, 10 Z is O, X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, X3is H, and R3is H. In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, X3is H, and R3is H. 15 In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, X3is H, and R3is H. In some embodiments, W is N, Y is CH, R1is -CH=CHF, R2is isopropyl, Z is O, X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, X320 is H, and R3is H. In some embodiments, W is CH, Y is CH, R1is -CH=CHF, R2is isopropyl, Z is O, X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is , , isopr3 3 opyl, Z is O, X is H, and R is H. 25 In some embodiments, isopropyl, Z is O, X3is H, and R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Z is O, X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Z is O, X3is H, and R3is H. 5 In some embodiments, isopropyl, Z is O, X3is H, and R3is H. isopro3 3 pyl, Z is O, X is H, and R is H. In some embodiments, W is N, Y is N, R1and R2form a group selected from: 10 In some embodiments, W is CH, Y is N, R1and R2form a group selected from: In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is CH2, X3is H, and R3is H. 15 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is CH2, X3is H, and R3is H. In some embodiments, W is CH, Y is N, Z is NH, X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is ethyl, Z is NH, X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is isopropyl, Z is NH, X3is H, and R3is H. 20 In some embodiments, W is CH, Y is N, R2is isopropyl, Z is NH, X3is H, and R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is NH, X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is NH, X3is H, and R3is H. 5 In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Ring A is , X3is H, and R3is H. In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, Ring A is , X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Ring A is 10 , X3is H, and R3is H. In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, Ring A is 15 In some embodiments, W is N, Y is CH, R1is isopropyl, R2is isopropyl, Ring A is is In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, Ring A is 20 In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Ring In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Ring 5 In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, Ring A is 10 In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, Ring A is 15 In some embodiments, W is N, Y is N, R1and R2form a group selected from: In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is 20 Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, Z is O, Ring A is 5 In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, Z is O, Ring A In some embodiments, W is N, Y is CH, R1is isopropyl, R2is isopropyl, Z is O, Ring 10 In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, Z is O, Ring 15 In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is 20 isopropyl, Z is O, Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, Ring 5 In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, Ring 10 In some embodiments, W is N, Y is N, R1and R2form a group selected from: 15 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is NH, Ring A In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Ring A is 20 , X3is H, and R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, Ring A is , X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Ring A is , X3is H, and R3is H. 5 In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, Ring A is , X3is H, and R3is H. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Ring A is , X3is H, and R3is H. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Ring A is 10 In some embodiments, W is N, Y is CH, R1is isopropyl, X3is H, and R3is H. R2is isopropyl, Ring In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Ring A is , X3is H, and R3is H. 15 In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, Ring A is , X3is H, and R3is H. In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2,R2is isopropyl, Ring In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, 20 Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Ring In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Ring 5 CH2-CH2-CH2-N(CH3)2, or -CH2-CH2-CH2-CH2-CH2-N(CH3)2. In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Ring In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2,R2is isopropyl, 10 In some embodiments, W is N, Y is N, R1is -CH2-phenyl, R2is isopropyl, Ring A is , X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is CH2-CN, R2is isopropyl, Ring A is , X3is H, and R3is H. 15 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one OH and one methyl group, R2is isopropyl, Ring A is , X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one CN and one methyl group, R2is isopropyl, Ring A is , X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one methoxy 20 group, R2is isopropyl, Ring A is , X3is H, and R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H-pyrazol- 1-yl group, R2is isopropyl, Ring A is , X3is H, and R3is -CH3. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group, R2is isopropyl, Ring A is , X3is H, and R3is -CH3. 5 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group and one methyl group, R2is isopropyl, Ring A is , X3is H, and R3is -CH3. In some embodiments, W is N, Y is N, R1is -CH2-phenyl, R2is isopropyl, Z is O, Ring 10 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one OH and one methyl group, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is H. 15 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one CN and one methyl group, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one methoxy group, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H-pyrazol- 20 1-yl group, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is -CH3. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is -CH3. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group and one methyl group, R2is isopropyl, Z is O, Ring A is H, and R3is -CH3. 5 In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2,R2is isopropyl, . W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2,R2is isopropyl, , X3is H, and R3is , or 10 . In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2,R2is isopropyl, Ring CH2-CH2-CH2-N(CH2-CH3)2. In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2,R2is isopropyl, 15 Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is ethyl,R2is isopropyl, Z is O, Ring A is In some embodiments, W is CH, Y is N, R1is ethyl,R2is isopropyl, Ring A is 5 , X3is H, and R3is -CH2-CH2-CH2-S(=O)2Me. In some embodiments, W is CH, Y is N, R1is ethyl,R2is isopropyl, Z is O, Ring A is , X3is H, and R3is -CH2-CH2-CH2-S(=O)2Me. In some embodiments, W is N, Y is N, R1is ethyl,R2is isopropyl, Ring A is , 10 In some embodiments, W is N, Y is N, R1is ethyl,R2is isopropyl, Z is O, Ring A is Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1is ethyl,R2is isopropyl, Ring A is In some embodiments, W is N, Y is N, R1is ethyl,R2is isopropyl, Z is O, Ring A is 5 In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2,R2is isopropyl, 10 In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2,R2is isopropyl, Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2,R2is isopropyl, , In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2,R2is isopropyl, 5 10 In some embodiments, ,3 3 , X is H, and R is Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1is methyl, R2is isopropyl, Z is O, Ring A is 5 In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, X3is H, and 10 . In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, X3is H, 5 10 . Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, X3is H, and In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is 5 In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, X3is H, and In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is 10 In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , and X3is -CH2-O-CH2-CHF2. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, X3is -CH2- O-CH2-CHF2, and R3is H. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is 15 , X3is -CH2-O-CH2-CHF2, and R3is H. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , and X3is -CH2-CH2-S(O)2-CH3or -CH2-CH2-CH2-S(O)2-CH3. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, X3is -CH2- CH2-S(O)2-CH3or -CH2-CH2-CH2-S(O)2-CH3, and R3is H. 20 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , X3is -CH2-CH2-S(O)2-CH3or -CH2-CH2-CH2-S(O)2-CH3, and R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, X3is -CH2- CH2-S(O)2-CH3or -CH2-CH2-CH2-S(O)2-CH3, and R3is methyl. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , X3is -CH2-CH2-S(O)2-CH3or -CH2-CH2-CH2-S(O)2-CH3, and R3is methyl. 5 In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , and X3is -CH2-CH2-CH2-O-CHF2. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, X3is X3is - CH2-CH2-CH2-O-CHF2, and R3is H. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is 10 , X3is -CH2-CH2-CH2-O-CHF2, and R3is H. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, X3is -CH2- CH2-CH2-O-CHF2, and R3is methyl. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , X3is -CH2-CH2-CH2-O-CHF2, and R3is methyl. 15 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , and X3is -CH2-O-CH2-CH2-N(CH3)2. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, X3is -CH2- O-CH2-CH2-N(CH3)2, and R3is H. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is 20 , X3is -CH2-O-CH2-CH2-N(CH3)2, and R3is H. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , and X3is -CH2-CH2-OH. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, X3is -CH2- CH2-OH, and R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , X3is -CH2-CH2-OH, and R3is H. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , and X3is -CH2-CH2-CH2-N(CH3)2. 5 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, X3is -CH2- CH2-CH2-N(CH3)2, and R3is methyl. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , X3is -CH2-CH2-CH2-N(CH3)2, and R3is methyl. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is 10 , and X3is -CH2-CH2-NH-C(O)-CH3. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, X3is -CH2- CH2-NH-C(O)-CH3, and R3is H. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is 15 20 Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, X3is In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Ring A is 5 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Ring A is In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, 10 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, Ring A is , X3is H, and R3is H. In some embodiments, W is N, Y is CH, R1is -CH=CHF, R2is isopropyl, Ring A is , X3is H, and R3is H. 5 In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, Ring A is , X3is H, and R3is H. In some embodiments, W is CH, Y is CH, R1is -CH=CHF, R2is isopropyl, Ring A is 10 In some embodiments, W is N, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, 15 Ring In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, In some embodiments, 5 In some embodiments, W is N, Y is N, R1and R2form a group selected from: In some embodiments, W is CH, Y is N, R1and R2form a group selected from: In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is 10 , X3is H, and R3is H. In some embodiments, W is N, Y is CH, R1is ethyl, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is CH, R1is ethyl, R2is isopropyl, Z is O, Ring A 5 In some embodiments, W is N, Y is CH, R1is isopropyl, R2is isopropyl, Z is O, Ring In some embodiments, W is CH, Y is CH, R1is isopropyl, R2is isopropyl, Z is O, Ring 10 In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring In some embodiments, W is N, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring 15 In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring In some embodiments, W is CH, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, Z is O, Ring A is , X3is methyl, ethyl, or isopropyl, and R3is H. In some embodiments, W is CH, Y is CH, R1is -CH2-CF3, or -CH2-CHF2, R2is 20 isopropyl, Z is O, Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, Ring 5 In some embodiments, W is CH, Y is N, R1is -CH=CHF, R2is isopropyl, Z is O, Ring In some embodiments, W is CH, Y is CH, R1is -CH=CHF, R2is isopropyl, Z is O, Ring In some embodiments, 10 In some embodiments, isopropyl, Z is O, Ring In some embodiments, W is N, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, 15 Z is O, Ring In some embodiments, W is CH, Y is N, R1is cyclopropyl or cyclobutyl, R2is isopropyl, Z is O, Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, , , or isopropyl, Z is O, Ring In some embodiments, , , or isopropyl, Z is O, Ring 5 In some embodiments, W is N, Y is N, R1and R2form a group selected from: Ring In some embodiments, W is CH, Y is N, R1and R2form a group selected from: Ring In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is CH2, Ring A is 10 , X3is H, and R3is H. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is CH2, Ring A is In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is CH2, Ring A is , X3is H, and R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Z is CH2, Ring 5 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is NH, Ring A In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Ring A is 10 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is 15 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, X3is -CH2-CH2- CH2(OH), and R3is H. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, X3is -CH2- 20 CH2-CH2(OH), and R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Ring A is , X3is -CH2-CH2-CH2(OH), and R3is H. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , X3is -CH2-CH2-CH2(OH), and R3is H. 5 In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, and R3is 10 methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1and R2form a group selected from: methyl, ethyl, or isopropyl. 15 In some embodiments, W is CH, Y is N, R1and R2form a group selected from: methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, and R3is 20 methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Z is O, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is O, and R3is methyl, ethyl, or isopropyl. 25 In some embodiments, W is N, Y is N, R1is -CH2-phenyl, R2is isopropyl, Z is O, and R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is -CH2-CN, R2is isopropyl, Z is O, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one OH and one methyl group, Z is O, and R3is H. 5 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one CN and one methyl group, Z is O, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one methoxy group, R2is isopropyl, Z is O, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H-pyrazol- 10 1-yl group, R2is isopropyl, Z is O, and R3is -CH3. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group, R2is isopropyl, Z is O, and R3is -CH3. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group and one methyl group, R2is isopropyl, Z is O, and R3is -CH3. 15 In some embodiments, W is N, Y is N, R1and R2form a group selected from: methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1and R2form a group selected from: methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Ring A is 20 , and R3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Ring A is , and R3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1and R2form a group selected from: Attorney Docket No. SYND-060 / 001WO 327830-2818 methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is and R3is methyl, ethyl, or isopropyl. 5 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is O, Ring A is , and R3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1and R2form a group selected from: methyl, ethyl, or isopropyl. 10 In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Ring A is , and R3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Ring A is , and R3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Ring A is 15 , and R3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Ring A is ethyl, or isopropyl. W is N, Y is N, R1is -CH2-phenyl, R2is isopropyl, Ring A is Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is -CH2-CN, R2is isopropyl, Z is O, Ring In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one OH and one methyl group, Z is O, Ring 5 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one CN and one methyl group, Z is O, Ring In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one methoxy group, R2is isopropyl, Ring A is , and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H-pyrazol- 10 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group, R2is isopropyl, Ring A is , and R3is -CH3. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- 15 imidazol-1-yl group and one methyl group, R2is isopropyl, Ring A is - CH3. In some embodiments, W is N, Y is N, R1and R2form a group selected from: isopropyl. 20 In some embodiments, W is CH, Y is N, R1and R2form a group selected from: Attorney Docket No. SYND-060 / 001WO 327830-2818 methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , and R3is methyl, ethyl, or isopropyl. 5 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , and R3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Z is O, Ring A is , and R3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is O, Ring 10 A is , and R3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is -CH2-phenyl, R2is isopropyl, Z is O, Ring 15 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one OH and one methyl group, R2is isopropyl, Z is O, Ring A is , and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one CN and one methyl group, R2is isopropyl, Z is O, Ring A is , and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one methoxy 20 group, R2is isopropyl, Z is O, Ring A is , and R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H-pyrazol- 1-yl group, R2is isopropyl, Z is O, Ring A is , and R3is -CH3. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group, R2is isopropyl, Z is O, Ring A is , and R3is -CH3. 5 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group and one methyl group, Z is O, R2is isopropyl, Ring A is R3is -CH3. In some embodiments, W is N, Y is N, R1and R2form a group selected from: methyl, 10 ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1and R2form a group selected from: methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, X3is H, and R3is 15 methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, X3is H, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, X3is H, and R3is methyl, ethyl, or isopropyl. 20 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, X3is H, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1and R2form a group selected from: methyl, ethyl, or isopropyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1and R2form a group selected from: methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, X3is H, and R3is methyl, ethyl, or isopropyl. 5 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, X3is H, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Z is O, X3is H, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is O, X3is 10 H, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1and R2form a group selected from: methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1and R2form a group selected from: 15 methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Ring A is , X3is H, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Ring A is 20 , X3is H, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Ring A is , X3is H, and R3is methyl, ethyl, or isopropyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Ring A is , X3is H, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1and R2form a group selected from: methyl, 5 ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1and R2form a group selected from: methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is 10 , X3is H, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is methyl, ethyl, or isopropyl. 15 In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is O, Ring , X3is H, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1and R2form a group selected from: methyl, ethyl, or isopropyl. 20 In some embodiments, W is CH, Y is N, R1and R2form a group selected from: Attorney Docket No. SYND-060 / 001WO 327830-2818 methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Ring A is , X3is H, and R3is methyl, ethyl, or isopropyl. 5 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Ring A is , X3is H, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Ring A is , X3is H, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Ring A is 10 In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Z is O, Ring A is In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2,R2is isopropyl, Ring 15 In some embodiments, Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is N, Y is N, R1is -CH2-CF3, or -CH2-CHF2, R2is isopropyl, 5 . In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Ring A is , X3is H, and R3is methyl, ethyl, or isopropyl. 10 In some embodiments, W is N, Y is N, R1and R2form a group selected from: ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1and R2form a group selected from: 15 In some embodiments, W is CH, Y is N, R1and R2form a group selected from: Attorney Docket No. SYND-060 / 001WO 327830-2818 methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is methyl, ethyl, or isopropyl. 5 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is isopropyl, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1is isopropyl, R2is isopropyl, Z is O, Ring 10 A is , X3is H, and R3is methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1and R2form a group selected from: methyl, ethyl, or isopropyl. In some embodiments, W is CH, Y is N, R1and R2form a group selected from: 15 methyl, ethyl, or isopropyl. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is 5 In some embodiments, W is N, Y is N, R1is -CH2-CHF2, R2is isopropyl, Z is O, Ring In some embodiments, W is N, Y is N, R1is , R2is isopropyl, Z is O, Ring A In some embodiments, W is N, Y is N, R1is -CH2-CF3, R2is isopropyl, Z is O, Ring A 10 In some embodiments, W is CH, Y is N, R1is -CH2-CN, R2is isopropyl, Z is O, Ring In some embodiments, W is CH, Y is N, R1is -CH2-CN, R2is isopropyl, Z is O, Ring 15 In some embodiments, W is N, Y is N, R1is -CH2-phenyl, R2is isopropyl, Z is O, Ring Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one OH and one methyl group, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is H. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one methoxy group, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is H. 5 In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is methyl. In some embodiments, W is N, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is -CD3. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one OH and 10 one methyl group, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is methyl. In some embodiments, W is CH, Y is N, R1is -CH2-CN, R2is isopropyl, Z is O, Ring methyl. In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, Z is O, Ring A is methyl. 15 In some embodiments, W is CH, Y is N, R1is , R2is isopropyl, Z is O, Ring A is , X3is H, and R3is H. In some embodiments, isopropyl, Z is O, Ring A is , X3is H, and R3is methyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, 5 In some embodiments, W is CH, Y is N, R1is ethyl, R2is isopropyl, In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one CN and 10 one methyl group, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is H. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, isopropyl, Z is O, Ring A is , X3is H, and R3is methyl. In some embodiments, isopropyl, Z is O, Ring A is , X3is H, and R3is H. 5 In some embodiments, isopropyl, Z is O, Ring A is , X3is H, and R3is H. In some embodiments, isopropyl, Z is O, Ring A is , X3is H, and R3is methyl. In some embodiments, isopropyl, Z is O, Ring A is 10 , X3is H, and R3is methyl. In some embodiments, W is CH, Y is N, R1is , R2is isopropyl, Z is O, Ring A is , X3is H, and R3is methyl. Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is , R2is isopropyl, Z is O, Ring A methyl. In some embodiments, isopropyl, Z is O, Ring A is 5 , X3is H, and R3is methyl. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H-pyrazol- 1-yl group, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is methyl. In some embodiments, W is CH, Y is N, R1is cyclobutyl substituted by one 1H- imidazol-1-yl group, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is methyl. 10 In some embodiments, W is CH, Y is N, R1is one 1H-imidazol-1-yl group and one methyl group, R2is isopropyl, Z is O, Ring A is , X3is H, and R3is methyl. In some embodiments, W is CH, Y is N, R1is isopropyl, Z is O, Ring A 15 Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, W is CH, Y is N, R1is isopropyl, Z is O, Ring A 5 In some embodiments, W is CH, Y is N, R1is isopropyl, Z is O, Ring A In some embodiments, W is CH, Y is N, R1is isopropyl, Z is O, Ring A is , X3is H, and R3is methyl. In some embodiments, the compound is of Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, or III combined with any of the embodiments 10 described herein. 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.

[0006] Attorney Docket No. SYND-060 / 001WO 327830-2818 Table 1. Representative Compounds of the Present Disclosure Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 4 4 4 4 4 N-(Cyanomethyl)-5-fluoro-N-isopropyl-2-((4-(6- ((6-methyl-5,6,7,8-tetrahydro-1,6-naphthyridin-4- yl)oxy)-2-azaspiro[3.3]heptan-2-yl)pyrimidin-5- 442 yl)oxy)benzamide (E2)-2-((4-(6-((5-(3-(5-Oxa-2-azaspiro[3.4]octan- 2-yl)propyl)-6-methyl-5,6,7,8-tetrahydro-1,6- naphthyridin-4-yl)oxy)-2-azaspiro[3.3]heptan-2- 443 yl)pyrimidin-5-yl)oxy)-N-ethyl-5-fluoro-N- isopropylbenzamide Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 Attorney Docket No. SYND-060 / 001WO 327830-2818 In some embodiments, a compound according to any embodiments herein (e.g., Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, and III, and Table 1) exhibits an inhibition activity against the binding of menin and MLL. In some embodiments, a compound 5 according to any embodiments herein (e.g., Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, and III, and Table 1) exhibits an inhibition activity against the binding of menin and Attorney Docket No. SYND-060 / 001WO 327830-2818 MLL. In some embodiments, a compound according to any embodiments herein e.g., Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, and III, and Table 1) exhibits an inhibition activity against the binding of menin and MLL which is useful in the treatment and / or prevention of one or more diseases in which menin and MLL play a role. 5 In some embodiments, a compound according to any embodiments herein (e.g., Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, and III, and Table 1) exhibits low hERG binding. In some embodiments, a compound according to any embodiments herein (e.g., Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, and III, and Table 1) minimizes hERG binding and is useful for the treatment of one or more diseases in which menin and MLL 10 play a role. Without being bound to any theory, one of the primary causes of QT prolongation is thought to be blockage of the hERG potassium channel in cardiac myocytes. In some embodiments, the compounds of the present disclosure (e.g., Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, and III, and Table 1) do not significantly block the hERG potassium channel. 15 In some embodiments, the compounds of the present disclosure (e.g., Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, and III, and Table 1) do not significantly block the hERG potassium channel (e.g., an IC50greater than 1 μM, 5 μM, 10 μM, 15 μM, 20 μM, 25 μM, 30 μM, 35 μM, 40 μM, or 50 μM) as measured by a standard patch clamp hERG assay. In some embodiments, the compounds of the present disclosure (e.g., Formulae I, Ia, 20 Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, and III, and Table 1) do not significantly block the hERG potassium channel (e.g., a compound of the invention has an IC50greater than 1 μM, 5 μM, 10 μM, 15 μM, 20 μM, 25 μM, 30 μM, 35 μM, 40 μM, or 50 μM for the hERG potassium channel). In some embodiments and without wishing to be bound to any theory, the present 25 disclosure is directed to inhibitors of the menin-MLL interaction comprising a pyrrolidine moiety (e.g., Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IId, IIe, IIf, and III, and Table 1) where the pyrrolidine moiety has been found to reduce hERG inhibition. In some embodiments and without wishing to be bound to any theory, the present disclosure is directed to inhibitors of the menin-MLL interaction comprising a piperidine 30 moiety (e.g., Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, and III, and Table 1) where the piperidine moiety has been found to reduce hERG inhibition. In some embodiments and without wishing to be bound to any theory, the present disclosure is directed to inhibitors of the menin-MLL interaction (e.g., Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, and III, and Table 1) which are resistant to metabolism. In Attorney Docket No. SYND-060 / 001WO 327830-2818 some embodiments and without wishing to be bound to any theory, the present disclosure is directed to inhibitors of the menin-MLL interaction (e.g., Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, and III, and Table 1) which are resistant to metabolism, where the metabolites are inhibitors of the hERG potassium channel. In some embodiments and without 5 wishing to be bound to any theory, the present disclosure is directed to inhibitors of the menin- MLL interaction (e.g., Formulae I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, and III, and Table 1) which are resistant to metabolism, where the metabolism decreases the bioavailability of the inhibitor. In some embodiments and without wishing to be bound to any theory, the present disclosure is directed to inhibitors of the menin-MLL interaction (e.g., Formulae I, Ia, 10 Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, and III, and Table 1) which are resistant to metabolism, where the metabolism decreases the bioavailability of the inhibitor and the corresponding metabolites are more effective (e.g., by IC50, etc.) at binding the hERG potassium channel. In some embodiments, one or more hydrogen atoms in any of the compounds of 15 Formula I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, or III may be replaced with one or more deuterium atoms. In some embodiments, the pharmaceutically acceptable salt of the compound of Formula I, Ia, Ib, Ic, Id, Ie, If, II, IIa, IIb, IIc, IId, IIe, IIf, or III is a hydrochloride salt or a 2,2,2,trifluoroacetate salt. 20 Another aspect is an isotopically labeled compound of any of the formulae delineated herein. Such compounds have one or more isotopic atoms (e.g.,3H,2H,14C,13C,18F,35S,32P, 125I, and131I) introduced into the compound. Such compounds are useful for drug metabolism studies and diagnostics, as well as therapeutic applications. In some embodiments, the compound is an isotopic derivative of any one of the compounds described in Table 1, or a 25 pharmaceutically acceptable salt thereof. It is understood that the deuterium labeled compound comprises a deuterium atom having an abundance of deuterium that is substantially greater than the natural abundance of deuterium, which is 0.015%. In some embodiments, the deuterium labeled compound has a deuterium enrichment 30 factor for each deuterium atom of at least 3500 (52.5% deuterium incorporation at each deuterium atom), at least 4000 (60% deuterium incorporation), at least 4500 (67.5% deuterium incorporation), at least 5000 (75% deuterium), at least 5500 (82.5% deuterium incorporation), at least 6000 (90% deuterium incorporation), at least 6333.3 (95% deuterium incorporation), at least 6466.7 (97% deuterium incorporation), at least 6600 (99% deuterium incorporation), Attorney Docket No. SYND-060 / 001WO 327830-2818 or at least 6633.3 (99.5% deuterium incorporation). As used herein, the term “deuterium enrichment factor” means the ratio between the deuterium abundance and the natural abundance of a deuterium. It is understood that the deuterium labeled compound can be prepared using any of a 5 variety of art-recognized techniques. For example, the deuterium labeled compound can generally be prepared by carrying out the procedures disclosed in the Schemes and / or in the Examples described herein, by substituting a deuterium labeled reagent for a non-deuterium labeled reagent. A compound of the present disclosure or a pharmaceutically acceptable salt or solvate 10 thereof that contains the aforementioned deuterium atom(s) is within the scope of the disclosure. Further, substitution with deuterium (i.e., 2H) may afford certain therapeutic advantages resulting from greater metabolic stability, e.g., increased in vivo half-life or reduced dosage requirements. For the avoidance of doubt, it is to be understood that, where in this specification a 15 group is qualified by “described herein”, the said group encompasses the first occurring and broadest definition as well as each and all of the particular definitions for that group. Potency can also be determined by IC50value. A compound with a lower IC50value, as determined under substantially similar conditions, is more potent relative to a compound with a higher IC50value. 20 Potency can also be determined by EC50value. A compound with a lower EC50value, as determined under substantially similar conditions, is more potent relative to a compound with a higher EC50 value. The compounds of the application are defined herein by their chemical structures and / or chemical names. Where a compound is referred to by both a chemical structure and a chemical 25 name, and the chemical structure and chemical name conflict, t...

Claims

Attorney Docket No. SYND-060 / 001WO 327830-2818 CLAIMS What is claimed is:

1. A compound of Formula (I),a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein: W is N or CH; Y is N or CH; R1is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C12 cycloalkyl, C6-C10 aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’); R2is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, or N(R4a’)(R4b’); R1and R2optionally form a 3- to 12-membered heterocyclyl, wherein the heterocyclyl is optionally substituted with one or more C1-C6 alkyl, halo, OH, or CN; Z is O, CH2, or NH; Ring A is 6- to 10-membered aryl or 6- to 10-membered heteroaryl, wherein the 6- to 10-membered aryl or 6- to 10-membered heteroaryl is optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy;Attorney Docket No. SYND-060 / 001WO 327830-2818 X3is H, C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocyclyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b); R3is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more R3a, or R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 12-membered heterocyclyl 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), C1-C6alkyl, C3-C12cycloalkyl, C1-C6alkoxy, C6- C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein the C1-C6alkyl, C3-C12cycloalkyl, C6-C10aryl, 3- to 12-membered heterocyclyl 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-C6alkyl that is optionally substituted with O(R4a), and 3- to 12- membered heterocyclyl that is optionally substituted with oxo; each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6-C10aryl 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-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted with C1-C6alkoxy or C(O)N(R4a’)(R4b’); each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl; and n is 1, 2, or 3.

2. The compound of claim 1, wherein R2is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12- membered heterocyclyl, wherein the C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, or N(R4a’)(R4b’).Attorney Docket No. SYND-060 / 001WO 327830-2818 3. The compound of claim 1 or 2, wherein R2is C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more halo, OH, oxo, CN, or N(R4a’)(R4b’).

4. The compound of any one of the preceding claims, wherein R2is isopropyl.

5. The compound of claim 1, wherein R1and R2form a group selected from:

6. A compound of Formula (II),Formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein: W is N or CH; Y is N or CH; R1is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’); Z is O, CH2, or NH;Attorney Docket No. SYND-060 / 001WO 327830-2818 Ring A is 6- to 10-membered aryl or 6- to 10-membered heteroaryl, wherein the 6- to 10-membered aryl or 6- to 10-membered heteroaryl is optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy; X3is H, C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocyclyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b); R3is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more R3a, or R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen atom to which it is connected, wherein the 3- to 12-membered heterocyclyl 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), C1-C6alkyl, C3-C12cycloalkyl, C1-C6alkoxy, C6- C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein the C1-C6alkyl, C3-C12cycloalkyl, C6-C10aryl, 3- to 12-membered heterocyclyl 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-C6alkyl that is optionally substituted with O(R4a), and 3- to 12- membered heterocyclyl that is optionally substituted with oxo; each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6-C10aryl 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-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted with C1-C6alkoxy or C(O)N(R4a’)(R4b’); each R4a’ and R4b’ is independently H, C1-C6 alkyl, C3-C12 cycloalkyl, or 3- to 12- membered heterocyclyl; and n is 1, 2, or 3.

7. The compound of any one of the preceding claims, wherein W is N.Attorney Docket No. SYND-060 / 001WO 327830-2818 8. The compound of any one of the preceding claims, wherein W is CH.

9. The compound of any one of the preceding claims, wherein Y is N.

10. The compound of any one of the preceding claims, wherein Y is CH.

11. The compound of any one of the preceding claims, wherein R1is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, C1- C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’).

12. The compound of any one of the preceding claims, wherein R1is C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl, the C3-C12cycloalkyl, or the 3- to 12-membered heterocyclyl is optionally substituted with one or more halo, OH, oxo, CN, C1-C6alkyl, C1-C6alkoxy, C6-C10aryl, 5- to 10-membered heteroaryl, or N(R4a’)(R4b’).

13. The compound of any one of the preceding claims, wherein R1is C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl, the C3-C12cycloalkyl, or the 3- to 12-membered heterocyclyl is optionally substituted with one or more halo.

14. The compound of any one of claims 1-4 and 6-13, wherein R1is methyl or ethyl.

15. The compound of any one of claims 1-4 and 6-13, wherein R1is isopropyl.

16. The compound of any one of claims 1-4 and 6-13, wherein R1is 2,2-difluoroethyl.Attorney Docket No. SYND-060 / 001WO 327830-281818. The compound of any one of claims 1-4 and 6-13, wherein R1is -CH2-CN, or -CH2- phenyl.

19. The compound of any one of claims 1-4 and 6-12, wherein R1is cyclobutyl substituted by one OH and one methyl group, cyclobutyl substituted by one CN and one methyl group, cyclobutyl substituted by one methoxy group, cyclobutyl substituted by one 1H-pyrazol-1-yl group, cyclobutyl substituted by one 1H-imidazol-1-yl group, or cyclobutyl substituted by one 1H-imidazol-1-yl group and one methyl group.

20. The compound of any one of the preceding claims, wherein Z is O, CH2, or NH.

21. The compound of any one of the preceding claims, wherein Z is O.

22. The compound of any one of claims 1-20, wherein Z is CH2.

23. The compound of any one of claims 1-20, wherein Z is NH.

24. The compound of any one of the preceding claims, wherein Ring A is 6- to 10- membered aryl or 6- to 10-membered heteroaryl, wherein the 6- to 10-membered aryl or 6- to 10-membered heteroaryl is optionally substituted with one or more C1-C6alkyl, halo, OH, CN, or C1-C6alkoxy.Attorney Docket No. SYND-060 / 001WO 327830-2818 25. The compound of any one of the preceding claims, wherein Ring A is 6- to 10- membered aryl or 6- to 10-membered heteroaryl.

26. The compound of any one of the preceding claims, wherein Ring A is.

27. The compound of any one of claims 1-25, wherein Ring A is.

28. The compound of any one of claims 1-25, wherein Ring A is.

29. The compound of any one of the preceding claims, wherein30. The compound of any one of the preceding claims, wherein X3is H, C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more halo, 3- to 12-membered heterocyclyl, S(=O)2R4a, OR4a, oxo, CN, C(=O)N(R4a)(R4b), or N(R4a)(R4b),and wherein each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6-C10aryl 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-C6alkyl, C3-C12cycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted with C1-C6alkoxy or C(O)N(R4a’)(R4b’).

31. The compound of any one of the preceding claims, wherein X3is H or C1-C6alkyl.Attorney Docket No. SYND-060 / 001WO 327830-2818 32. The compound of claims 1-30, wherein X3is -CH2-OCH3, -CH2-CH2-OCH3, -CH2- CH2-CH2-OCH3, -CH2-O-CH2-CHF2, -CH2-CH2-CH2-O-CHF2, -CH2-O-CH2-CH2-N(CH3)2, - CH2-CH2-S(O)2-CH3or -CH2-CH2-CH2-S(O)2-CH3, -CH2-CH2-NH-C(O)-CH3, -CH2-CH2-33. The compound of claims 1-31, wherein X3is methyl.

34. The compound of any one of the preceding claims, wherein R3is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C3-C12cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl is optionally substituted with one or more R3a, wherein: 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-C6 alkyl, C3-C12 cycloalkyl, C1-C6 alkoxy, C6- C10aryl, 3- to 12-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein the C1-C6alkyl, C3-C12cycloalkyl, C6-C10aryl, 3- to 12-membered heterocyclyl 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-C6alkyl that is optionally substituted with O(R4a), and 3- to 12- membered heterocyclyl that is optionally substituted with oxo; each R4ais independently H, CN, or C1-C6alkyl optionally substituted with one or more halo, C6-C10aryl 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-C6 alkyl, C3-C12 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-C6alkyl is optionally substituted with C1-C6alkoxy or C(O)N(R4a’)(R4b’); and each R4a’ and R4b’ is independently H, C1-C6alkyl, C3-C12cycloalkyl, or 3- to 12- membered heterocyclyl.

35. The compound of any one of claims 1-34, wherein R3is C1-C6alkyl that is optionally substituted with one or more R3a, wherein:Attorney Docket No. SYND-060 / 001WO 327830-2818 each R3ais independently N(R4a)(R4b), S(=O)2R4b’, or 3- to 12-membered heterocyclyl that is optionally substituted with one or more substituent independently selected from C1-C6alkyl optionally substituted with one or more halo, and O(R4a’); each R4aand R4bis independently H, or C1-C6alkyl; and each R4a’ and R4b’ is independently H or C1-C6alkyl.

36. The compound of any one of claims 1-35, wherein R3is methyl, ethyl, or isopropyl.

37. The compound of any one of claims 1-34, wherein R3is -CH2-CH2-N(CH3)2, -CH2- CH2-CH2-N(CH3)2, -CH2-CH2-CH2-CH2-N(CH3)2, -CH2-CH2-CH2-CH2-CH2-N(CH3)2, -CH2- CH2-S(=O)2Me, or -CH2-CH2-CH2-S(=O)2Me.

38. The compound of any one of claims 1-34, wherein R3is H.

39. The compound of any one of claims 1-34, wherein R3, , , ,,Attorney Docket No. SYND-060 / 001WO 327830-2818Attorney Docket No. SYND-060 / 001WO 327830-281842. The compound of any one of claims 1-34, wherein R3is H.

43. The compound of any one of claims 1-33, wherein R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen atom to which it is connected.

44. The compound of claim 43, wherein, or.

45. The compound of any one of the preceding claims, wherein n is 1.

46. The compound of any one of the preceding claims, wherein n is 2.

47. The compound of any one of the preceding claims, wherein n is 3.Attorney Docket No. SYND-060 / 001WO 327830-2818 48. A compound of Formula (III),a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein: W is N or CH; Y is N or CH; R1is C1-C6alkyl or C3-C12cycloalkyl, wherein the C1-C6alkyl or the C3-C12cycloalkyl is optionally substituted with one or more halo, C1-C6alkoxy, C6-C10aryl, or 5- to 10- membered heteroaryl; R2is C1-C6alkyl; Z is O, CH2, or NH; Ring A is 6- to 10-membered aryl or 6- to 10-membered heteroaryl; X3is H or C1-C6alkyl; R3is H or C1-C6alkyl, wherein the C1-C6alkyl is optionally substituted with one or more R3aor R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen atom to which it is connected; each R3ais independently N(R4a)(R4b) or 3- to 12-membered heterocyclyl, wherein the 3- to 12-membered heterocyclyl is optionally substituted with one or more substituent independently selected from C1-C6alkyl and O(R4a’); each R4aand R4bis independently C1-C6alkyl; R4a’ is H; and n is 1 or 2.

49. The compound of claim 48, wherein W is N.Attorney Docket No. SYND-060 / 001WO 327830-2818 50. The compound of claim 48, wherein W is CH.

51. The compound of any one of claims 48-50, wherein Y is N.

52. The compound of any one of claims 48-50, wherein Y is CH.

53. The compound of any one of claims 48-52, wherein R1is C1-C6alkyl optionally substituted with one or more halo.

54. The compound of any one of claims 48-52, wherein R1is C3-C12cycloalkyl optionally substituted with one or more halo.

55. The compound of any one of claims 48-54, wherein R2is C1-C6 alkyl.

56. The compound of any one of claims 48-54, wherein R2is C1-C6alkyl.

57. The compound of any one of claims 48-56, wherein Z is O.

58. The compound of any one of claims 48-56, wherein Z is NH.

59. The compound of any one of claims 48-56, wherein Z is CH2.

60. The compound of any one of claims 48-59, wherein Ring A is 6-membered aryl or 6- membered heteroaryl.Attorney Docket No. SYND-060 / 001WO 327830-2818 62. The compound of any one of claims 48-61, wherein X3is H.

63. The compound of any one of claims 48-61, wherein X3is C1-C6alkyl.

64. The compound of any one of claims 48-63, wherein R3is H.

65. The compound of any one of claims 48-63, wherein R3is C1-C6alkyl optionally substituted with one or more R3a.

66. The compound of claim 65, wherein R3ais N(R4a)(R4b) and wherein each R4aand R4bis independently C1-C6 alkyl.

67. The compound of claim 65, wherein each R3ais independently 3- to 12-membered heterocyclyl optionally substituted with one or more substituent independently selected from C1-C6alkyl and O(R4a’).

68. The compound of claim 67, wherein each R3ais independently 3- to 12-membered heterocyclyl optionally substituted with one or more substituent independently selected from C1-C6alkyl and OH.

69. The compound of any one of claims 48-63, wherein R3forms a 3- to 12-membered heterocyclyl with the carbon atom next to the nitrogen atom to which it is connected.

70. The compound of any one of claims 48-69 wherein n is 1.

71. The compound of any one of claims 48-69 wherein n is 2.

72. A compound as shown in Table 1 or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

73. A compound as shown in Table 1 or a pharmaceutically acceptable salt thereof.

74. A compound as shown in Table 1.Attorney Docket No. SYND-060 / 001WO 327830-2818 75. A compound as shown in Table 1 or a pharmaceutically acceptable salt thereof, wherein the salt is hydrochloric acid.

76. The compound according to any one of the preceding claims, wherein the compound is useful for the treatment of a cancer and wherein the compound minimizes hERG binding.

77. A pharmaceutical composition comprising a compound of any one of claims 1 to 49, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

78. A pharmaceutical composition comprising a salt or crystalline form of any one of claims 1-48, and at least one pharmaceutically acceptable carrier.

79. A method of inhibiting the interaction between menin and MLL comprising contacting the menin and MLL with a compound of any one of claims 1 to 76 or a pharmaceutical composition of either claim 77 or 78.

80. A method of treating cancer in a patient comprising administering to the patient a compound of any one of claims 1 to 76 or a pharmaceutical composition of either claim 77 or 78.

81. The method of claim 80, wherein the cancer is a hematological cancer.

82. The method of either claim 80 or 81, wherein the cancer is a leukemia.

83. The method of either claim 80 or 81, wherein the cancer is a lymphoma.

84. The method of either claim 80 or 81, 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, acuteAttorney Docket No. SYND-060 / 001WO 327830-2818 nonlymphocytic leukemia, chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), therapy related leukemia, myelodysplastic syndrome (MDS), myeloproliferative disease (MPD), myeloproliferative 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, Sézary Syndrome, hairy cell leukemia, T-cell prolymphocytic 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.

85. The method of either claim 80 or 81, wherein the cancer is an abstract nucleophosmin (NPM1)-mutated acute myeloid leukemia (i.e., NPM1mutacute myloid leukemia).

86. The method of either claim 80 or 81, wherein the cancer is a rearranged mixed lineage (KMT2A-rearranged) leukemia (MLL-r).

87. A compound of any of claims 1-76 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of either claim 77 or 78, for use in treating or preventing a disease caused by, or associated with, menin expression, activity, and / or function.

88. A compound of any of claims 1-76 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of either claim 77 or 78, for use in treating or preventing cancer.

89. Use of a compound of any of claims 1-76 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of either claim 77 or 78, for treating or preventing a disease caused by, or associated with, menin expression, activity, and / or function.

90. Use of a compound of any of claims 1-76 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of either claim 77 or 78, in the manufacture of a medicament for treating or preventing a disease caused by, or associated with, menin expression, activity, and / or function.

91. Use of a compound of any of claims 1-76 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of either claim 77 or 78, for treating or preventing cancer.Attorney Docket No. SYND-060 / 001WO 327830-2818 92. Use of a compound of any of claims 1-76 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of either claim 77 or 78, in the manufacture of a medicament for treating or preventing cancer.

93. A kit comprising a compound of any of claims 1-76 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of either claim 77 or 78 and instructions for its use.

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