Erastin ketone analogs and uses thereof

Abstract

Disclosed herein are compounds, compositions, and methods useful for modulating ferroptosis and treatment of diseases, such as cancer, using such compounds, compositions, and methods. (I)

Description

[0001] ERASTIN KETONE ANALOGS AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of and priority to International Patent Application No. PCT / CN2023 / 106777, filed on July 11, 2023, which is incorporated by reference hereby in its 5 entirety for all purposes. FIELD The present disclosure relates to compounds, compositions, and methods useful for the treatment of diseases including cancer. Also provided are compounds useful for modulating ferroptosis. 10 BACKGROUND Ferroptosis, a non-apoptotic type of cell death that is iron-dependent and accompanied by accumulation of lipid peroxides, is closely related to the pathophysiological processes of diseases, such as cancer. Unlike apoptosis, which many cancer cells can evade, ferroptosis is lethal to cancer cells that have become dependent on suppression of ferroptosis for survival, 15 including drug-resistant cancer cells and aggressive cancer cells. There is a need to develop compounds that modulate ferroptosis (e.g., induce ferroptosis) for the treatment of diseases, such as cancer. SUMMARY The present disclosure features compounds, or pharmaceutically acceptable salts thereof 20 (e.g., compounds of Formula A, Formula B, and Formula C, and subformulas thereof; and compounds of Table 1 and Table 2; and pharmaceutically acceptable salts thereof), and methods useful for treating diseases (e.g., cancer). The disclosure also features compositions comprising compounds useful for the treatment of diseases (e.g., cancer). Disclosed herein, in some embodiments, is a compound of Formula A: or a pharmaceutically acceptable salt thereof, wherein: 5 each of X1, X2, X3, and X4is independently N or CR1; each of X5and X6is independently N or CR2; each instance of R1is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R1a, C2-20alkenyl optionally substituted with 1-4 instances of R1a, or C2-20alkynyl optionally substituted with 1-4 instances of R1a; 10 each instance of R1ais independently RB; each instance of R2is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R2a, C2-20alkenyl optionally substituted with 1-4 instances of R2a, or C2-20alkynyl optionally substituted with 1-4 instances of R2a; each instance of R2ais independently RB; 15 R3is C1-6alkyl, C1-6haloalkyl, C3-6carbocyclyl, or 3-6–membered heterocyclyl having 1- 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R3is optionally substituted with 1-6 instances of R3a; each R3ais independently halo, –CN, –NO2, C1-6alkyl, or C1-6alkoxy; each of R4and R5is independently H, halo, –CN, –NO2, C1-6alkyl, C1-6haloalkyl, or C3-620 carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3-6carbocyclylene; Ring A is C3-14carbocyclylene or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R6is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R6a, C2-20alkenyl optionally substituted with 1-4 instances of R6a, or C2-20alkynyl optionally substituted with 1-4 instances of R6a; each instance of R6ais independently RB; 5 L0is –O–,–NRL1–, –C(O)–, or –CRL2RL3–; L1is absent, –O–, –NRL1–, –C(O)–, or –CRL2RL3–; L2is absent, –O–, –NRL1–, or –CRL2RL3–; each instance of RL1is independently H or C1-6alkyl; each instance of RL2and RL3is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-610 carbocyclyl, or RL2and RL3are taken together with the atom to which each is attached to form C3-6carbocyclylene; R7is Ring B is C6-14aryl or 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 15 each instance of R8is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R8a, C2-20alkenyl optionally substituted with 1-4 instances of R8a, or C2-20alkynyl optionally substituted with 1-4 instances of R8a; each instance of R8ais independently RB; Y1is –C(O)– or –CRY1RY2–; 20 each instance of RY1and RY2is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-6carbocyclyl, or RY1and RY2are taken together with the atom to which each is attached to form C3-6carbocyclylene; Y2is absent or Ring D is C6-14 arylene, C3-14carbocyclylene, 5-14–membered heteroarylene having 1-6 25 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R9is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R9a, C2-20alkenyl optionally substituted with 1-4 instances of R9a, or C2-20alkynyl 30 optionally substituted with 1-4 instances of R9a; each instance of R9ais independently RB; Y3is absent, –C(O)–, or –CRY1RY2–; each instance of RY1and RY2is independently H or C1-6alkyl; R10is H, halo, –CN, –NO2, –OH, –NH2, C1-6haloalkyl, C1-20alkyl, C1-20heteroalkyl, C2- 520alkenyl, C2-20alkynyl, or Ring E is C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R11is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 10 instances of R11a, C2-20alkenyl optionally substituted with 1-4 instances of R11a, or C2-20alkynyl optionally substituted with 1-4 instances of R11a; each instance of R11ais independently RB; each instance of RAis independently C1-6haloalkyl, halo, –CN, –NO2, –SF5, –C(O)Raa, – C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, – 15 S(O)2F, –S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, or –SRaa; each instance of RBis independently halo, –CN, –NO2, –SF5, –C(O)Raa, –C(O)ORaa, – C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, –S(O)2F, – S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, –SRaa, or –Si(Raa)3; each instance of Raais independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-2020 heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of Rbbis independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-20heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms 25 independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; m is 0, 1, 2, 3, 4, 5, or 6; n is 0, 1, 2, 3, 4, 5, or 6; o is 0, 1, 2, 3, 4, 5, or 6; and 30 p is 0, 1, 2, 3, 4, 5, or 6. Disclosed herein, in some embodiments, is a compound of Formula B: or a pharmaceutically acceptable salt thereof, wherein: 5 each of X1, X2, X3, and X4is independently N or CR1; each of X5and X6is independently N or CR2; each instance of R1is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R1a, C2-20alkenyl optionally substituted with 1-4 instances of R1a, or C2-20alkynyl optionally substituted with 1-4 instances of R1a; 10 each instance of R1ais independently RB; each instance of R2is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R2a, C2-20alkenyl optionally substituted with 1-4 instances of R2a, or C2-20alkynyl optionally substituted with 1-4 instances of R2a; each instance of R2ais independently RB; 15 R3is C1-6alkyl, C1-6haloalkyl, C3-6carbocyclyl, or 3-6–membered heterocyclyl having 1- 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R3is optionally substituted with 1-6 instances of R3a; each R3ais independently halo, –CN, –NO2, C1-6alkyl, or C1-6alkoxy; each of R4and R5is independently H, halo, –CN, –NO2, C1-6alkyl, C1-6haloalkyl, or C3-620 carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3-6carbocyclylene; Ring A is C3-14carbocyclylene or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R6is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R6a, C2-20alkenyl optionally substituted with 1-4 instances of R6a, or C2-20alkynyl optionally substituted with 1-4 instances of R6a; each instance of R6ais independently RB; 5 L0is –O–,–NRL1–, –C(O)–, or –CRL2RL3–; L1is absent, –O–, –NRL1–, –C(O)–, or –CRL2RL3–; L2is absent, –O–, –NRL1–, or –CRL2RL3–; each instance of RL1is independently H or C1-6alkyl; each instance of RL2and RL3is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-610 carbocyclyl, or RL2and RL3are taken together with the atom to which each is attached to form C3-6carbocyclylene; R7is Ring B is C6-14aryl or 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 15 each instance of R8is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R8a, C2-20alkenyl optionally substituted with 1-4 instances of R8a, or C2-20alkynyl optionally substituted with 1-4 instances of R8a; each instance of R8ais independently RB; Y1is –C(O)– or –CRY1RY2–; 20 each instance of RY1and RY2is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-6carbocyclyl, or RY1and RY2are taken together with the atom to which each is attached to form C3-6carbocyclylene; Y2is absent or Ring D is C6-14arylene, C3-14carbocyclylene, 5-14–membered heteroarylene having 1-6 25 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R9is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R9a, C2-20alkenyl optionally substituted with 1-4 instances of R9a, or C2-20alkynyl 30 optionally substituted with 1-4 instances of R9a; each instance of R9ais independently RB; Y3is absent, –C(O)–, or –CRY1RY2–; each instance of RY1and RY2is independently H or C1-6alkyl; R10is H, halo, –CN, –NO2, –OH, –NH2, C1-6haloalkyl, C1-20alkyl, C1-20heteroalkyl, C2- 520alkenyl, C2-20alkynyl, or Ring E is C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R11is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 10 instances of R11a, C2-20alkenyl optionally substituted with 1-4 instances of R11a, or C2-20alkynyl optionally substituted with 1-4 instances of R11a; each instance of R11ais independently RB; each instance of RAis independently C1-6haloalkyl, halo, –CN, –NO2, –SF5, –C(O)Raa, – C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, – 15 S(O)2F, –S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, or –SRaa; each instance of RBis independently halo, –CN, –NO2, –SF5, –C(O)Raa, –C(O)ORaa, – C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, –S(O)2F, – S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, –SRaa, or –Si(Raa)3; each instance of Raais independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-2020 heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of Rbbis independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-20heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms 25 independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; m is 0, 1, 2, 3, 4, 5, or 6; n is 0, 1, 2, 3, 4, 5, or 6; o is 0, 1, 2, 3, 4, 5, or 6; and 30 p is 0, 1, 2, 3, 4, 5, or 6. Disclosed herein, in some embodiments, is a compound of Formula C: or a pharmaceutically acceptable salt thereof, wherein: 5 each of X1, X2, X3, and X4is independently N or CR1; each of X5and X6is independently N or CR2; each instance of R1is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R1a, C2-20alkenyl optionally substituted with 1-4 instances of R1a, or C2-20alkynyl optionally substituted with 1-4 instances of R1a; 10 each instance of R1ais independently RB; each instance of R2is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R2a, C2-20alkenyl optionally substituted with 1-4 instances of R2a, or C2-20alkynyl optionally substituted with 1-4 instances of R2a; each instance of R2ais independently RB; 15 R3is C1-6alkyl, C1-6haloalkyl, C3-6carbocyclyl, or 3-6–membered heterocyclyl having 1- 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R3is optionally substituted with 1-6 instances of R3a; each R3ais independently halo, –CN, –NO2, C1-6alkyl, or C1-6alkoxy; each of R4and R5is independently H, halo, –CN, –NO2, C1-6alkyl, C1-6haloalkyl, or C3-620 carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3-6carbocyclylene; Ring A is C3-14carbocyclylene or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R6is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R6a, C2-20alkenyl optionally substituted with 1-4 instances of R6a, or C2-20alkynyl optionally substituted with 1-4 instances of R6a; each instance of R6ais independently RB; 5 L0is –O–,–NRL1–, –C(O)–, or –CRL2RL3–; L1is absent, –O–, –NRL1–, –C(O)–, or –CRL2RL3–; L2is absent, –O–, –NRL1–, or –CRL2RL3–; each instance of RL1is independently H or C1-6alkyl; each instance of RL2and RL3is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-610 carbocyclyl, or RL2and RL3are taken together with the atom to which each is attached to form C3-6carbocyclylene; R7is Ring B is C6-14aryl or 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 15 each instance of R8is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R8a, C2-20alkenyl optionally substituted with 1-4 instances of R8a, or C2-20alkynyl optionally substituted with 1-4 instances of R8a; each instance of R8ais independently RB; Y1is –C(O)– or –CRY1RY2–; 20 each instance of RY1and RY2is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-6carbocyclyl, or RY1and RY2are taken together with the atom to which each is attached to form C3-6carbocyclylene; Y2is absent or Ring D is C6-14arylene, C3-14carbocyclylene, 5-14–membered heteroarylene having 1-6 25 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R9is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R9a, C2-20alkenyl optionally substituted with 1-4 instances of R9a, or C2-20alkynyl 30 optionally substituted with 1-4 instances of R9a; each instance of R9ais independently RB; Y3is absent, –C(O)–, or –CRY1RY2–; each instance of RY1and RY2is independently H or C1-6alkyl; R10is H, halo, –CN, –NO2, –OH, –NH2, C1-6haloalkyl, C1-20alkyl, C1-20heteroalkyl, C2- 520alkenyl, C2-20alkynyl, or Ring E is C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R11is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 10 instances of R11a, C2-20alkenyl optionally substituted with 1-4 instances of R11a, or C2-20alkynyl optionally substituted with 1-4 instances of R11a; each instance of R11ais independently RB; each instance of RAis independently C1-6haloalkyl, halo, –CN, –NO2, –SF5, –C(O)Raa, – C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, – 15 S(O)2F, –S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, or –SRaa; each instance of RBis independently halo, –CN, –NO2, –SF5, –C(O)Raa, –C(O)ORaa, – C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, –S(O)2F, – S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, –SRaa, or –Si(Raa)3; each instance of Raais independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-2020 heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of Rbbis independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-20heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms 25 independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; m is 0, 1, 2, 3, 4, 5, or 6; n is 0, 1, 2, 3, 4, 5, or 6; o is 0, 1, 2, 3, 4, 5, or 6; and 30 p is 0, 1, 2, 3, 4, 5, or 6. Disclosed herein, in some embodiments, is a pharmaceutical composition comprising a Disclosed herein, in some embodiments, is a process for providing a compound disclosed herein or an effective amount of a pharmaceutical composition disclosed herein. Disclosed herein, in some embodiments, is a method of treating a disease (e.g., a ferroptosis-mediated disease or cancer) in a subject in need thereof, comprising administering to 5 the subject an effective amount of a compound disclosed herein or an effective amount of a pharmaceutical composition disclosed herein. Disclosed herein, in some embodiments, is a compound disclosed herein or a composition disclosed herein, in the manufacture of a medicament for the treatment of a disease (e.g., ferroptosis-mediated disease or cancer). 10 Still other aspects and embodiments will become apparent to those of skill in the art from the disclosure herein, which is simply illustrative and not restrictive. Thus, other embodiments will be recognized by one of skill in the art without departing from the spirit and scope of the disclosure. BRIEF DESCRIPTION OF THE DRAWINGS 15 FIG.1 shows the absolute configuration and ORTEP structure of the 3-(5-(2-(2H-1,2,3- triazol-2-yl)acetyl)-2-isopropoxyphenyl)-2-(piperazin-1-ylmethyl)pyrido[2,3-d]pyrimidin-4(3H)- one intermediate that leads to EXAMPLE 64. FIG.2 is a table summarizing the X-ray crystallographic data for the 3-(5-(2-(2H-1,2,3- triazol-2-yl)acetyl)-2-isopropoxyphenyl)-2-(piperazin-1-ylmethyl)pyrido[2,3-d]pyrimidin-4(3H)- 20 one intermediate that leads to EXAMPLE 64. FIG.3 is a table listing atomic coordinates (x 10^4) and equivalent isotropic displacement parameters (A^2 x 10^3) for the 3-(5-(2-(2H-1,2,3-triazol-2-yl)acetyl)-2- isopropoxyphenyl)-2-(piperazin-1-ylmethyl)pyrido[2,3-d]pyrimidin-4(3H)-one intermediate that leads to EXAMPLE 64. 25 FIG.4 a table listing atomic coordinates (x 10^4) and equivalent isotropic displacement parameters (A^2 x 10^3) for the 3-(5-(2-(2H-1,2,3-triazol-2-yl)acetyl)-2-isopropoxyphenyl)-2- (piperazin-1-ylmethyl)pyrido[2,3-d]pyrimidin-4(3H)-one intermediate that leads to EXAMPLE 64. FIG.5 a table listing atomic coordinates (x 10^4) and equivalent isotropic displacement30 parameters (A^2 x 10^3) for the 3-(5-(2-(2H-1,2,3-triazol-2-yl)acetyl)-2-isopropoxyphenyl)-2- (piperazin-1-ylmethyl)pyrido[2,3-d]pyrimidin-4(3H)-one intermediate that leads to EXAMPLE 64. DETAILED DESCRIPTION As generally described herein, the present disclosure features compounds, (e.g., compounds of Formula A, Formula B, and Formula C, and subformulas thereof, and compounds of Table 1 and Table 2, and pharmaceutically acceptable salts thereof), compositions, and 5 methods useful for treating ferroptosis-mediated diseases, such as cancer. Definitions The following definitions apply to the terms as used to describe the present disclosure, unless otherwise indicated or apparent from context. Unless explicitly indicated otherwise, or apparent from context, the terms below do not exclude the meaning that the term has acquired in 10 the art to which it pertains. The definitions below are provided to facilitate the description of the disclosure, but they are not intended to limit the scope of the disclosure. Unless otherwise indicated, all numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the 15 numerical parameters set forth in this specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present disclosure The terms “a,” “an,” and “the” refer to one or to more than one, unless context indicates otherwise. Similarly, the term “or” is intended to include “and”, unless context indicates otherwise. 20 As used herein, the terms “about” and “approximately” refer to a value that is within 10% above or below the value being described. For example, the term “about 5 mg” indicates a range of from 4.5 mg to 5.5 mg. The terms “disease,” “disorder,” and “condition” are used interchangeably herein. As used herein, the term “effective amount” of a compound refers to an amount sufficient 25 to elicit a beneficial or desired biological response (e.g., clinical results such as treating cancer). As such, the effective amount may be sufficient, e.g., to reduce or ameliorate the severity or duration of a disease, or symptoms thereof, related to ferroptosis; or to prevent the advancement of symptoms related to diseases related to ferroptosis. An effective amount also includes the amount of a compound that avoids or substantially attenuates undesirable side effects. As will 30 be appreciated by those of ordinary skill in this art, the effective amount of a compound disclosed herein may vary depending on such factors as the desired biological endpoint, the pharmacokinetics of the compound, the disease being treated, the mode of administration, and the age, weight, health, and condition of the subject. An effective amount encompasses therapeutic and prophylactic treatment. As used herein, and unless otherwise specified, a “therapeutically effective amount” of a compound is an amount sufficient to provide a therapeutic benefit in the treatment of a disease, 5 disorder, or condition, or symptoms thereof, or to delay or minimize one or more symptoms associated with the disease, disorder, or condition, or symptoms thereof. A therapeutically effective amount of a compound means an amount of the compound which provides a therapeutic benefit in the treatment of the disease, disorder, or condition, or symptoms thereof. The term “therapeutically effective amount” can encompass an amount that improves overall 10 therapy or an amount that reduces or avoids symptoms or causes of disease or condition. As used herein, the term “ferroptosis-mediated disease” or “ferroptosis-mediated disorder” refers to a disease or disorder in which ferroptosis plays a role (e.g., a disease or disorder that is characterized by abnormal ferroptosis or suppression of ferroptosis). A ferroptosis-mediated disease or disorder may be completely or partially mediated by modulating 15 ferroptosis. In particular, a ferroptosis-mediated disease or disorder is one in which modulation of ferroptosis results in some effect on the underlying disease or disorder (e.g., administration of a ferroptosis modulator results in improvement in the disease or disorder, or symptoms thereof). As used herein, the term “modulate” or “modulating” or “modulation” refers to inhibition or potentiation of ferroptosis. A “modulator” (e.g., a modulator compound) may be, for 20 example, a compound that reduces the occurrence of ferroptosis or a compound that increases the occurrence of ferroptosis. As used herein, the term “pharmaceutical composition” refers to a formulation (e.g., medicinal formulation) that contains at least one active ingredient (e.g., a compound disclosed herein, e.g., a compound of Formula A, Formula B, or Formula C, or any subformula thereof, a 25 compound of Table 1 or Table 2, or a compound described in the Examples, or a pharmaceutically acceptable salt thereof) as well as one or more excipients or diluents to enable the active ingredient suitable for the method of administration. The pharmaceutical composition of the present disclosure includes pharmaceutically acceptable components that are compatible with a compound disclosed herein (e.g., a compound of Formula A, Formula B, or Formula C, or 30 any subformula thereof, a compound of Table 1 or Table 2, or a compound described in the Examples, or a pharmaceutically acceptable salt thereof). As used herein, the term “pharmaceutically acceptable” refers to compounds, compositions, dosage forms, or materials which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of a subject without excessive allergic response, irritation, toxicity, or other problem or complication, commensurate with a reasonable benefit / risk ratio. In some embodiments, the term “pharmaceutically acceptable” means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, and more 5 particularly in humans. As used herein, the term “pharmaceutically acceptable excipient” refers to a substance or material other than the compounds disclosed herein (e.g., compounds of Formula A, Formula B, or Formula C, or any subformula thereof, compounds of Table 1 or Table 2, and compounds described in the Examples, and a pharmaceutically acceptable salt thereof) that is included in the 10 compositions disclosed herein. Excipients are generally nontoxic to the subject and compatible with the other ingredients of the composition. Excipients include, but are not limited to, adjusting agents, adjuvants, antiadherents, antimicrobial agents, antioxidants, binders, buffers, carriers, coatings, compression aids, diluents, disintegrants, dispersing agents, dyes, emollients, emulsifiers, encapsulating materials, fillers, flavors, fragrances, glidants, lubricants, 15 preservatives, salts, solvents, sorbents, stabilizers, surfactants, suspending agents, and sweeteners. For example, a pharmaceutically acceptable excipient may be a vehicle capable of suspending or dissolving a compound disclosed herein. Exemplary excipients are found, e.g., in Remington’s Pharmaceutical Sciences, 15thEd., Mack Publ. Co., Easton, PA (1975). As used herein, the term “pharmaceutically acceptable salt” refers to those salts which 20 are, within the scope of sound medical judgment, suitable for use in contact with the tissues of a subject without excessive allergic response, irritation, toxicity, or other problem or complication, commensurate with a reasonable benefit / risk ratio. The term "pharmaceutically acceptable salt” is meant to include salts of the compounds disclosed herein that are prepared with relatively nontoxic acids or bases, depending on the particular substituents found on the compounds. 25 When compounds contain relatively acidic functionalities, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suitable inert solvent. When compounds contain relatively basic functionalities, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either neat or in a suitable inert solvent. 30 Certain compounds contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts. Exemplary pharmaceutically acceptable salts are found, e.g., in Berge, et al. (J. Pharm. Sci.1977, 66(1), 1; and Gould, P.L., Int. J. Pharmaceutics 1986, 33, 201-217, each of which is hereby incorporated by reference in its entirety. As used herein, the term “subject” refers to a human (i.e., a male or female of any age group) or non-human primate, or other mammal, such as but not limited to dog, cat, horse, cow, pig, turkey, goat, fish, monkey, chicken, rat, mouse, or sheep. In some embodiments, the subject is human. In some embodiments, the subject is non-human. The terms “human,” “patient,” and 5 “subject” are used interchangeably herein. As used herein, the term “treat” or “treating” a disease or disorder refers to alleviating, ameliorating, delaying, inhibiting, preventing, reversing, slowing down, or stopping the aggravation, deterioration, onset, or progression of the disease or disorder, or a condition or symptom associated with the disease or disorder. In some embodiments, treatment slows the 10 progression of the disease (e.g., cancer), improves the subject's outcome, or eliminates the disease, or symptoms thereof. In some embodiments, treatment of a disease (e.g., cancer) in a subject alleviates or ameliorates one or more symptoms or conditions associated with the disease (e.g., cancer). In some embodiments, treatment of a disease (e.g., cancer) in a subject diminishes the extent of the disease. In some embodiments, treatment of a disease (e.g., cancer) in a subject 15 stabilizes (i.e., not worsening) the state of the disease (e.g., cancer). In some embodiments, treatment of a disease (e.g., cancer) in a subject prevents the spread of the disease (e.g., cancer). In some embodiments, treatment of a disease (e.g., cancer) in a subject delays or slows the progress of the disease (e.g., cancer), as compared to the state or the condition of the disease (e.g., cancer) in the absence of the treatment. 20 Chemical Definitions The following chemical definitions apply to the abbreviations and terms as used to describe the present disclosure, unless otherwise indicated or apparent from context. Unless explicitly indicated otherwise, or apparent from context, the terms below do not exclude the meaning that the term has acquired in the chemical arts. The definitions below are provided to 25 facilitate the description of the disclosure, but they are not intended to limit the scope of the disclosure. The abbreviations and terms used herein have their conventional meaning within the chemical arts. The structures and formulas set forth herein are constructed according to the standard rules of chemical valency known in the chemical arts. 30 Definitions of select chemical terms and functional groups are described in more detail below. The chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th Ed., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Thomas Sorrell, Organic Chemistry, University Science Books, Sausalito, 1999; Smith and March, March’s Advanced Organic Chemistry, 5th Edition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New 5 York, 1989; and Carruthers, Some Modern Methods of Organic Synthesis, 3rd Edition, Cambridge University Press, Cambridge, 1987. Compound Configuration Those skilled in the art will appreciate that compounds described herein can exist in one or more different isomeric (e.g., constitutional isomers, geometric isomers, stereoisomers, and 10 tautomers) or isotopic (e.g., one or more hydrogen substituted with deuterium) forms. Unless otherwise indicated, a depicted structure can be understood to represent any such isomeric or isotopic forms, individually or in combination. As used herein, the term “chiral” is used to describe a structure or a functional group of a structure (e.g., an sp3 carbon center) that has a non-superimposable mirror image. As used 15 herein, the term “achiral” is used to describe a structure or a functional group of a structure (e.g., an sp3 carbon center) that has a superimposable mirror image. As used herein, the term “isomer” refers to and includes a compound or structure with identical chemical formula but different atom connectivity (e.g., constitutional (structural) isomer) or spacial configuration (e.g., stereoisomer). Generally, isomers exhibit different 20 physical properties, such as optical rotation. As used herein, the term “constitutional isomer” or “structural isomer” refers to and includes a compound or structure with identical chemical formula but different atom connectivity. As used herein, the term “stereoisomer” refers to and includes a compound or structure 25 with identical chemical formula and identical atom connectivity but different spatial configuration (i.e., differ in positioning or arrangement of the atoms in space). Stereoisomers may be atropisomers, diastereomers, enantiomers, or geometric (or conformational) isomers. The term “stereoisomerically pure” or “pure stereoisomer” (e.g., atropisomerically pure or pure atropisomer; diastereomerically pure or pure diastereomer; or enantiomerically pure or pure 30 enantiomer) denotes that the compound (or a composition comprising the compound) comprises more than about 50% by weight or by mole fraction, more than about 55% by weight or by mole fraction, more than about 60% by weight or by mole fraction, more than about 65% by weight or by mole fraction, more than about 70% by weight or by mole fraction, more than about 75% by weight or by mole fraction, more than about 80% by weight or by mole fraction, more than about 85% by weight or by mole fraction, more than about 90% by weight or by mole fraction, more than about 91% by weight or by mole fraction, more than about 92% by weight or by mole fraction, more than about 93% by weight or by mole fraction, more than about 94% by weight or 5 by mole fraction, more than about 95% by weight or by mole fraction, more than about 96% by weight or by mole fraction, more than about 97% by weight or by mole fraction, more than about 98% by weight or by mole fraction, more than about 98.5% by weight or by mole fraction, more than about 99% by weight or by mole fraction, more than about 99.1% by weight or by mole fraction, more than about 99.2% by weight or by mole fraction, more than about 99.3% by 10 weight or by mole fraction, more than about 99.4% by weight or by mole fraction, more than about 99.5% by weight or by mole fraction, more than about 99.6% by weight or by mole fraction, more than about 99.7% by weight or by mole fraction, more than about 99.8% by weight or by mole fraction, more than about 99.9% by weight or by mole fraction, of the stereoisomer. In some embodiments, the weights are based upon total weight of all 15 stereoisomers of the compound. In some embodiments, the weights are based upon total weight of two stereoisomers of the compound. As used herein, the term “atropisomer” refers to a conformational stereoisomer that occurs when rotation about a single bond in the compound or structure is hindered or prevented to allow for isolation of conformers (i.e., the steric strain of the barrier of rotation allows for 20 isolation of conformers). For the compounds disclosed herein, the half-life (t1 / 2) or the rotational energy barrier (ΔG ) for interconversion about the single bond (e.g., chiral axis or axis of chirality) may be determined using methods known in the art. In some embodiments, the compounds disclosed herein have a half-life for interconversion about the single bond of t1 / 2≤ 1 s at room temperature (e.g., about 20 °C, about 21 °C, about 22 °C, about 23 °C, about 24 °C, 25 about 26 °C, or about 26 °C). In some embodiments, the compounds disclosed herein have a half-life for interconversion about the single bond of 1 s < t1 / 2≤ 9 months at room temperature (e.g., about 20 °C, about 21 °C, about 22 °C, about 23 °C, about 24 °C, about 26 °C, or about 26 °C). In some embodiments, the compounds disclosed herein have a half-life for interconversion about the single bond of t1 / 2> 9 months at room temperature (e.g., about 20 °C, 30 about 21 °C, about 22 °C, about 23 °C, about 24 °C, about 26 °C, or about 26 °C). In some embodiments, the compounds disclosed herein have a barrier of rotation for interconversion about the single bond of ΔG ≤ 20 kcal / mol. In some embodiments, the compounds disclosed herein have a barrier of rotation for interconversion about the single bond of 20 kcal / mol < ΔG ≤ 30 kcal / mol. In some embodiments, the compounds disclosed herein have a barrier of rotation for interconversion about the single bond of ΔG > 30 kcal / mol. Bold lines and dashed lines in the compounds disclosed herein indicate the portions of the structure that are hindered or restricted about a single bond. For example, the following illustrations refer to the same atropisomer: As used herein, the term “diastereomer” refers to a stereoisomer of a structure that is not the mirror image of the structure and that is not superimposable on the structure. Diastereomers generally contain more than one of a chiral moiety (e.g., a chiral center or a chiral axis). As used herein, the term “enantiomer” refers to the mirror image of a structure that is not 10 superimposable on the structure. A pair of enantiomers may contain a chiral center (e.g., an asymmetrically substituted sp3 carbon atom) or a chiral axis. A composition comprising a pure enantiomeric compound is substantially free of the other enantiomer or stereoisomers of the compound (i.e., a composition comprising a compound in enantiomeric excess). In other words, an “S” form of the compound is substantially free from the “R” form of the compound and is in 15 enantiomeric excess of the “R” form. “Racemate" or "racemic mixture" refers to a composition comprising both enantiomers of a compound, wherein such composition exhibits no optical activity (i.e., the composition does not rotate the plane of polarized light). As used herein, the term “geometric isomer” refers to an isomer that differs in the arrangement or orientation of atoms with respect to a double bond, ring, or other rigid structural 20 system. For example, atoms on each side of a carbon-carbon double bond may be in an E (substituents are on opposite sides of the carbon-carbon double bond) or Z (substituents are oriented on the same side) configuration. Many geometric isomers of, e.g., olefins and C=N double bonds can also be present in the compounds described herein, and all such stable isomers are contemplated in the present disclosure. Cis and trans geometric isomers of the compounds of 25 the present disclosure are described and may be isolated as a mixture of isomers or as separated isomeric forms. All stereoisomers of the compounds disclosed herein, including atropisomeric forms, diastereomeric forms, enantiomeric forms, and geometric (or conformational) isomeric forms, are contemplated within the scope of this disclosure. For example, the compounds described 30 herein can be in the form of an individual atropisomer, diastereomer, enantiomer, or geometric isomer, or can be in the form of a mixture of stereoisomers, including a racemic mixture and a mixture that is enriched in one or more stereoisomer. Unless otherwise stated, single stereoisomers, as well as mixtures of atropisomeric isomers, diastereomeric isomers, enantiomeric isomers, or geometric isomeric isomers of the compounds described herein are within the scope of the disclosure. A composition may comprise a compound described herein 5 as an individual isomer (e.g., stereoisomer) that is substantially free of other isomers (e.g., other stereoisomers). Alternatively, a composition may comprise a compound described herein as a mixture of one or more isomers e.g., stereoisomers). Unless otherwise indicated, the absolute stereochemistry of a chiral center (or asymmetric center) or a chiral axis is as depicted. When a disclosed compound is named or depicted by structure without indicating the 10 relative or absolute stereochemistry of the chiral moiety (e.g., chiral center or chiral axis), it is to be understood that the name or structure includes one isomer free of all other isomers; more than one isomer free of all other isomers; mixtures of isomers where all isomers are present in about the same amount by weight or by mole fraction; mixtures of isomers where one isomer is enriched relative to the other isomer(s); and mixtures of isomers where more than one isomer is 15 enriched relative to the other isomer(s). All forms are contemplated within the scope of this disclosure. As used herein, the term “tautomer” refers to one of two or more structural isomers which exist in equilibrium and which are readily converted from one isomeric form to another. It is understood that tautomers encompass valence tautomers and proton tautomers (also known 20 as prototrophic tautomers). Valence tautomerism includes interconversion via redistribution of electrons between isomeric forms. Proton tautomerism includes interconversion via migration of a proton (i.e., an isomeric protonation state having the same empirical formula and total charge as a reference form). In some embodiments, tautomeric forms result from the swapping of a single bond with an adjacent double bond and the concomitant migration of a proton. Examples 25 of moieties with prototrophic tautomeric forms are amide / imidic acid pairs, enamine / imine pairs, ketone / enol pairs, lactam / lactim pairs, and annular forms where a proton can occupy two or more positions of a heterocyclic system, such as, 1H-imidazole and 3H-imidazole; 1H-1,2,4-triazole, 2H-1,2,4-triazole, and 4H-1,2,4-triazole; 1H- isoindole and 2H-isoindole; and 1H- pyrazole and 2H-pyrazole. Unless otherwise stated, all tautomers of the compounds disclosed herein are 30 within the scope of the disclosure. In some embodiments, tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution. In some embodiments, tautomeric forms result from acetal interconversion. In some embodiments, one or more compounds disclosed herein may exist in different tautomeric forms. As will be clear from context, unless explicitly excluded, reference to such compounds encompasses all tautomeric forms. Unless otherwise stated, structures that differ only in the presence of one or more isotopically enriched atoms are contemplated within the scope of the disclosure. The term 5 “isotope” refers to an atom having the same atomic number but different mass number, resulting from a different number of neutrons in the nuclei. For example, isotopes of hydrogen include tritium (i.e.,3H) and deuterium (i.e.,2H or D). Exemplary isotopes that can be incorporated into compounds disclosed herein include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, and iodine, such as2H,3H,11C,13C,14C,13N,15N,15O, 1017O,18O,32P,33P,35S,18F,36Cl,123I, and125I. Isotopically labeled compounds can generally be prepared by following procedures analogous to those described herein for the presently disclosed compounds, by substituting an isotopically labeled reagent for a non-isotopically labeled reagent. In some embodiments, compounds disclosed herein comprise one or more asymmetric 15 centers or one or more chiral axes, and thus can exist in various isomeric forms, e.g., atropisomers, enantiomers, and / or diastereomers. For example, the compounds disclosed herein can be in the form of an individual stereoisomer, e.g., atropisomer, enantiomer, or diastereomer, or can be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomer. The present disclosure contemplates compounds 20 described herein as individual isomers substantially free of other isomers, and alternatively, as mixtures of various isomers. Select Functional Groups For any of the following terms, a number following an atomic symbol indicates that total number of atoms of that element that are present in a particular chemical moiety. As will be 25 understood, other atoms, such as hydrogen atoms or substituent groups as described herein, may be present to satisfy the valences of the atoms. For example, an unsubstituted C2alkyl group has the formula –CH2CH3. For compounds in which a variable appears more than once, each variable can be a different moiety selected from the Markush group defining the variable. For example, where a 30 structure is described having two R groups that are simultaneously present on the same compound, the two R groups can represent different functional groups or moieties selected from the Markush group defined for R. It will be understood that “substitution” or “substituted with” includes the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent. In general, the term “substituted” means that one or more hydrogens of the designated moiety are replaced with a suitable substituent. Unless otherwise indicated, a 5 “substituted” group may have a suitable substituent at each substitutable position of the group, and when more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at each position. Herein a phrase of the form “optionally substituted X” (e.g., optionally substituted alkyl) 10 is intended to be equivalent to “X, wherein X is optionally substituted” (e.g., “alkyl, wherein said alkyl is optionally substituted”). It is not intended to mean that the feature “X” (e.g., alkyl) per se is optional. Two or more substituents may optionally be joined to form aryl, heteroaryl, carbocyclyl, or heterocyclyl groups. Such ring-forming substituents are typically, though not necessarily, 15 found attached to a cyclic base structure. In some embodiments, the ring-forming substituents are attached to adjacent members of the base structure. For example, two ring-forming substituents attached to adjacent members of a cyclic base structure create a fused ring structure. In another embodiment, the ring-forming substituents are attached to a single member of the base structure. For example, two ring-forming substituents attached to a single member of a cyclic 20 base structure create a spirocyclic structure. In yet another embodiment, the ring-forming substituents are attached to non-adjacent members of the base structure. As used herein, the term “alkyl” refers to a saturated hydrocarbon monovalent radical having a straight chain or branched chain of 1 to 24 carbon atoms (“C1-24alkyl”). In some embodiments, an alkyl group has 1 to 20 carbon atoms (“C1-20alkyl”). In some embodiments, an 25 alkyl group has 1 to 16 carbon atoms (“C1-16alkyl”). In some embodiments, an alkyl group has 1 to 12 carbon atoms (“C1-C12alkyl”). In some embodiments, an alkyl group has 1 to 10 carbon atoms (“C1-10alkyl”). In some embodiments, an alkyl group has 1 to 8 carbon atoms (“C1-8alkyl”). In some embodiments, an alkyl group has 1 to 6 carbon atoms (“C1-6 alkyl”). In some embodiments, an alkyl group has 1 to 5 carbon atoms (“C1-5alkyl”). In some embodiments, an 30 alkyl group has 1 to 4 carbon atoms (“C1-4alkyl”). In some embodiments, an alkyl group has 1 to 3 carbon atoms (“C1-3alkyl”). In some embodiments, an alkyl group has 1 to 2 carbon atoms (“C1-2alkyl”). In some embodiments, an alkyl group has 1 carbon atom (“C1alkyl”). Examples of alkyl groups include, but are not limited to, methyl (C1), ethyl (C2), n–propyl (C3), isopropyl (C3), n–butyl (C4), tert–butyl (C4), sec–butyl (C4), iso–butyl (C4), n–pentyl (C5), 3–pentanyl (C5), amyl (C5), neopentyl (C5), 3–methyl–2–butanyl (C5), tertiary amyl (C5), n–hexyl (C6), n–heptyl (C7), and n–octyl (C8). Each instance of an alkyl group may be independently optionally substituted, i.e., unsubstituted (an “unsubstituted alkyl”) or substituted (a “substituted alkyl”) with one or more substituents (e.g., from 1 to 5 substituents, 1 to 4 substituents, 1 to 3 5 substituents, 1 to 2 substituents, or 1 substituent). In some embodiments, the alkyl group is unsubstituted alkyl. In some embodiments, the alkyl group is substituted alkyl. As used herein, the term “alkylene” refers to a divalent alkyl group. An exemplary C2alkyl group is –CH2CH3, while an exemplary C2alkylene group is –CH2CH2–. As used herein, the term “alkenyl” refers to an unsaturated hydrocarbon monovalent 10 radical having a straight chain or branched chain of 2 to 24 carbon atoms (“C2-24”), one or more carbon–carbon double bonds, and no triple bonds. In some embodiments, an alkenyl group has 2 to 20 carbon atoms (“C2-20alkenyl”). In some embodiments, an alkenyl group has 2 to 16 carbon atoms (“C2-16alkenyl”). In some embodiments, an alkenyl group has 2 to 12 carbon atoms (“C2-12alkenyl”). In some embodiments, an alkenyl group has 2 to 10 carbon atoms (“C2- 1510alkenyl”). In some embodiments, an alkenyl group has 2 to 8 carbon atoms (“C2-8alkenyl”). In some embodiments, an alkenyl group has 2 to 6 carbon atoms (“C2-6alkenyl”). In some embodiments, an alkenyl group has 2 to 5 carbon atoms (“C2-5alkenyl”). In some embodiments, an alkenyl group has 2 to 4 carbon atoms (“C2-4 alkenyl”). In some embodiments, an alkenyl group has 2 to 3 carbon atoms (“C2-3alkenyl”). In some embodiments, an alkenyl 20 group has 2 carbon atoms (“C2alkenyl”). The one or more carbon–carbon double bonds can be internal (e.g., as the carbon–carbon double bond in 2–butenyl) or terminal (e.g., as the carbon– carbon double bond in 1–butenyl). Examples of alkenyl groups include, but are not limited to, ethenyl (C2), 1–propenyl (C3), 2–propenyl (C3), 1–butenyl (C4), 2–butenyl (C4), butadienyl (C4), pentenyl (C5), pentadienyl (C5), hexenyl (C6), heptenyl (C7), octenyl (C8), and octatrienyl (C8). 25 Each instance of an alkenyl group may be independently optionally substituted, i.e., unsubstituted (an “unsubstituted alkenyl”) or substituted (a “substituted alkenyl”) with one or more substituents (e.g., from 1 to 5 substituents, 1 to 4 substituents, 1 to 3 substituents, 1 to 2 substituents, or 1 substituent). In some embodiments, the alkenyl group is unsubstituted alkenyl. In some embodiments, the alkenyl group is substituted alkenyl. 30 As used herein, the term “alkenylene” refers to a divalent alkenyl group. An exemplary C2alkenyl group is –CHCH2, while an exemplary C2alkenylene group is –CHCH–. As used herein, the term “alkynyl” refers to an unsaturated hydrocarbon monovalent radical having a straight chain or branched chain of 2 to 24 carbon atoms (“C2-24alkynyl”) and one or more carbon–carbon triple bonds. In some embodiments, an alkynyl group has 2 to 20 carbon atoms (“C2-20alkynyl”). In some embodiments, an alkynyl group has 2 to 16 carbon atoms (“C2-16alkynyl”). In some embodiments, an alkynyl group has 2 to 12 carbon atoms (“C2- 12alkynyl”). In some embodiments, an alkynyl group has 2 to 10 carbon atoms (“C2-10alkynyl”). In some embodiments, an alkynyl group has 2 to 8 carbon atoms (“C2-8alkynyl”). In 5 some embodiments, an alkynyl group has 2 to 6 carbon atoms (“C2-6alkynyl”). In some embodiments, an alkynyl group has 2 to 5 carbon atoms (“C2-5alkynyl”). In some embodiments, an alkynyl group has 2 to 4 carbon atoms (“C2-4alkynyl”). In some embodiments, an alkynyl group has 2 to 3 carbon atoms (“C2-3alkynyl”). In some embodiments, an alkynyl group has 2 carbon atoms (“C2alkynyl”). The one or more carbon–carbon triple bonds can be 10 internal (such as in 2–butynyl) or terminal (such as in 1–butynyl). Examples of alkynyl groups include, but are not limited to, ethynyl (C2), 1–propynyl (C3), 2–propynyl (C3), 1–butynyl (C4), and 2–butynyl (C4). Each instance of an alkynyl group may be independently optionally substituted, i.e., unsubstituted (an “unsubstituted alkynyl”) or substituted (a “substituted alkynyl”) with one or more substituents (e.g., from 1 to 5 substituents, 1 to 4 substituents, 1 to 3 15 substituents, 1 to 2 substituents, or 1 substituent). In some embodiments, the alkynyl group is unsubstituted alkynyl. In some embodiments, the alkynyl group is substituted alkynyl. As used herein, the term “alkynylene” refers to a divalent alkynyl group. An exemplary C2 alkynyl group is –C≡CH, while an exemplary C2 alkynylene group is –C≡C–. As used herein, the terms “alkoxyl” or “alkoxy” refer to an alkyl group, as defined above, 20 having an oxygen radical attached thereto. Representative alkoxy groups include, but are not limited to, methoxy, ethoxy, isopropoxy, and tert-butoxy. As used herein, “aryl” refers to a monovalent radical of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) ring system of 6–14 ring carbon atoms (“C6-14aryl”) having at least one aromatic ring and no heteroatoms in the ring system. In some embodiments, the aryl group is 25 completely aromatic (i.e., the entire ring system is aromatic). In some embodiments, an aryl group has six ring carbon atoms (“C6aryl”; e.g., phenyl). In some embodiments, an aryl group has ten ring carbon atoms (“C10aryl”; e.g., naphthyl such as 1–naphthyl and 2–naphthyl). In some embodiments, an aryl group has fourteen ring carbon atoms (“C14 aryl”; e.g., anthracyl). Examples of aryl groups include, but are not limited to, phenyl, naphthyl, anthracyl, indenyl, and 30 tetrahydronaphthyl. Each instance of an aryl group may be independently optionally substituted, i.e., unsubstituted (an “unsubstituted aryl”) or substituted (a “substituted aryl”) with one or more substituents (e.g., from 1 to 5 substituents, 1 to 4 substituents, 1 to 3 substituents, 1 to 2 substituents, or 1 substituent). In some embodiments, the aryl group is unsubstituted aryl. In some embodiments, the aryl group is substituted aryl. As used herein, the term “arylene” refers to a divalent aryl group. An exemplary C6aryl group is while an exemplary C6arylene group is As used herein, the term “carbocyclyl” refers to a monovalent radical of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) ring system of 3-14 ring carbon atoms (“C3-14carbocyclyl”) 5 having no heteroatoms in the ring system, wherein no ring in the ring system is aromatic. In some embodiments, a carbocyclyl group has 3-10 ring carbon atoms (“C3-10carbocyclyl”). In some embodiments, a carbocyclyl group has 3-8 ring carbon atoms (“C3-8carbocyclyl”). In some embodiments, a carbocyclyl group has 3-6 ring carbon atoms (“C3-6carbocyclyl”). In some embodiments, a carbocyclyl group has 5-10 ring carbon atoms (“C5-10carbocyclyl”). In some 10 embodiments, a carbocyclyl group is a saturated ring system (“cycloalkyl”; e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornyl, or adamantyl). In some embodiments, a carbocyclyl group is an unsaturated ring systems (“cycloalkenyl” or “cycloalkynyl”; e.g., cyclohexenyl or cyclooctynyl). In some embodiments, a carbocyclyl group comprises a spirocyclic ring system. In some embodiments, a carbocyclyl group comprises a 15 bridged ring system. In some embodiments, a carbocyclyl group comprises a fused ring system. Exemplary carbocyclyl groups include, without limitation, cyclopropyl (C3), cyclopropenyl (C3), cyclobutyl (C4), cyclobutenyl (C4), cyclopentyl (C5), cyclopentenyl (C5), cyclohexyl (C6), cyclohexenyl (C6), cyclohexadienyl (C6), cycloheptyl (C7), cycloheptenyl (C7), cycloheptadienyl (C7), cycloheptatrienyl (C7), cyclooctyl (C8), cyclooctenyl (C8), cubanyl (C8), 20 bicyclo[1.1.1]pentanyl (C5), bicyclo[2.2.2]octanyl (C8), bicyclo[2.1.1]hexanyl (C6), bicyclo[3.1.1]heptanyl (C7), cyclononyl (C9), cyclononenyl (C9), cyclodecyl (C10), cyclodecenyl (C10), octahydro–1H–indenyl (C9), decahydronaphthalenyl (C10), and spiro[4.5]decanyl (C10). Each instance of a carbocyclyl group may be independently optionally substituted, i.e., unsubstituted (an “unsubstituted carbocyclyl”) or substituted (a “substituted carbocyclyl”) with 25 one or more substituents (e.g., from 1 to 5 substituents, 1 to 4 substituents, 1 to 3 substituents, 1 to 2 substituents, or 1 substituent). In some embodiments, the carbocyclyl group is unsubstituted carbocyclyl. In certain embodiments, the carbocyclyl group is a substituted carbocyclyl. As used herein, the term “carbocyclylene” refers to a divalent carbocyclyl group. An exemplary C6carbocyclyl group is while an exemplary C6carbocyclylene group is 30 As used herein the term “cyano” refers to the radical –CN As used herein, the term “halo” or “halogen,” independently or as part of another functional group or substituent, refer to a fluorine (fluoro; F), chlorine (chloro; Cl), bromine (bromo; Br), or iodine (iodo; I) radical (i.e., –F, –Cl, –Br, or –I). As used herein, the term “haloalkyl” refers to alkyl, as defined above, substituted with 5 one or more (e.g., 1, 2, 3, 4, 5, or 6) halo groups. For example, “fluoroalkyl” refers to alkyl, as defined above, substituted with one or more fluoro groups. Examples of haloalkyl groups include, but are not limited to, –CH2F, –CHF2, –CF3, –CH2CF3, –CH2CH2CF3, and –CH(CF3)2. As used herein, the term “heteroalkyl” refers to an alkyl group, as defined herein, in which one or more carbon atoms (e.g., 1 to 12 carbon atoms, 1 to 10 carbon atoms, 1 to 8 carbon 10 atoms, 1 to 6 carbon atoms, 1 to 5 carbon atoms, 1 to 4 carbon atoms, 1 to 3 carbon atoms, 1 to 2 carbon atoms, or 1 carbon atom) have been replaced by heteroatoms, wherein each heteroatom is independently selected from the group consisting of O, N, P, Si, and S, wherein the N, P, or S atoms are optionally be oxidized, and wherein the N atom is optionally quaternized. Each heteroatom (i.e., O, N, P, Si, and S) may be located at any position of the heteroalkyl group. In 15 some embodiments, the heteroalkyl group comprises two or more consecutive heteroatoms (e.g., as found in –CH2NHOCH3and –CH2OSi(CH3)3). Where “heteroalkyl” is recited, followed by recitations of specific heteroalkyl groups (e.g., –OR or –NRR'), it will be understood that the terms heteroalkyl and –OR or –NRR' are not redundant or mutually exclusive. Rather, the specific heteroalkyl groups are recited to add clarity. Thus, the term “heteroalkyl” should not be 20 interpreted herein as excluding specific heteroalkyl groups, such as –OR or –NRR'. As used herein, the term “heteroalkylene” refers to a divalent heteroalkyl group. An exemplary C2heteroalkyl group is –OCH3, while an exemplary C2heteroalkylene group is – OCH2–. As used herein, the term “heteroaryl” refers to a monovalent radical of a monocyclic or 25 polycyclic (e.g., bicyclic or tricyclic) ring system of 5-14 atoms (“5-14–membered heteroaryl”) having at least one aromatic ring comprising one or more carbon atoms (e.g., 1 to 6 carbon atoms, 1 to 5 carbon atoms, 1 to 4 carbon atoms, 1 to 3 carbon atoms, 1 to 2 carbon atoms, or 1 carbon atom) and one or more heteroatoms (e.g., 1 to 6 heteroatoms, 1 to 5 heteroatoms, 1 to 4 heteroatoms, 1 to 3 heteroatoms, 1 to 2 heteroatoms, or 1 heteroatom), wherein each heteroatom 30 is independently selected from O, N, P, Si, and S, and wherein the N, P, or S atoms are optionally be oxidized. In some embodiments, the heteroaryl group is completely aromatic (i.e., the entire ring system is aromatic). In heteroaryl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon atom or nitrogen atom, as valency permits. In some embodiments, a heteroaryl group has five ring atoms (“5–membered heteroaryl”; e.g., pyrrolyl, imidazolyl, triazolyl, or tetrazolyl). In some embodiments, a heteroaryl group has six ring atoms (“6–membered heteroaryl”; e.g., pyridinyl, pyrimidinyl, or pyridinonyl). In some embodiments, a heteroaryl group has nine ring atoms (“9–membered heteroaryl”; e.g., In some embodiments, a heteroaryl group has ten ring H 5 atoms (“10–membered heteroaryl”; e.g., In some embodiments, a heteroaryl group is a 5-10–membered aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur. In some embodiments, a heteroaryl group is a 5-8–membered aromatic ring system having ring carbon atoms and 1–4 ring 10 heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur. In some embodiments, a heteroaryl group is a 5-6– membered aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6–membered heteroaryl has 1–3 ring 15 heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6– membered heteroaryl has 1–2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6–membered heteroaryl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur. Each instance of a heteroaryl group may be independently optionally substituted, i.e., unsubstituted (an “unsubstituted heteroaryl”) or substituted (a “substituted 20 heteroaryl”) with one or more substituents (e.g., from 1 to 5 substituents, 1 to 4 substituents, 1 to 3 substituents, 1 to 2 substituents, or 1 substituent). In some embodiments, the heteroaryl group is unsubstituted heteroaryl. In some embodiments, the heteroaryl group is substituted heteroaryl. As used herein, the term “heteroarylene” refers to a divalent heteroaryl group. An exemplary 6–membered heteraryl group is while an exemplary 6–membered 25 heterarylene group is . As used herein, the term “heterocyclyl” refers to a radical of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) ring system of 3-14 ring atoms (“3-14–membered heterocyclyl”) having one or more heteroatoms (e.g., 1 to 6 heteroatoms, 1 to 5 heteroatoms, 1 to 4 heteroatoms, 1 to 3 heteroatoms, 1 to 2 heteroatoms, or 1 heteroatom), wherein each heteroatom is 30 independently selected from O, N, P, Si, and S, and wherein the N, P, or S atoms are optionally be oxidized, and wherein no ring in the ring system is aromatic. In heterocyclyl groups comprising one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. In some embodiments, a heterocyclyl group is a saturated ring system (“heterocycloalkyl”; e.g., aziridinyl, azetidinyl, pyrrolidinyl, or piperidinyl). In some 5 embodiments, a heterocyclyl group is an unsaturated ring system (“heterocycloalkenyl” or “heterocycloalkynyl”; e.g., dihydropyranyl). In some embodiments, a heterocyclyl group comprises a spirocyclic ring system. In some embodiments, a heterocyclyl group comprises a bridged ring system. In some embodiments, a heterocyclyl group comprises a fused ring system. Heterocyclyl bicyclic ring systems can include one or more heteroatoms in one or both rings. In 10 some embodiments, a heterocyclyl group has five ring atoms (“5–membered heterocyclyl”; e.g., pyrrolinyl). In some embodiments, a heterocyclyl group has six ring atoms (“6–membered heterocyclyl”; e.g., piperidinyl or piperazinyl). In some embodiments, a heterocyclyl group has seven ring atoms (“7–membered heterocyclyl”; e.g., azepanyl). In some embodiments, a heterocyclyl group has eight ring atoms (“8–membered heterocyclyl”; e.g., azocanyl). In some 15 embodiments, a heterocyclyl group has nine ring atoms (“9–membered heterocyclyl”; e.g., In some embodiments, a heterocyclyl group has ten ring atoms (“10– membered heterocyclyl”; e.g., In some embodiments, a heterocyclyl group is a 5-10–membered ring system having ring carbon atoms and 1–4 ring heteroatoms provided in the ring system, wherein each heteroatom is independently selected from nitrogen, 20 oxygen, and sulfur. In some embodiments, a heterocyclyl group is a 5-8–membered ring system having ring carbon atoms and 1–4 ring heteroatoms provided in the ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur. In some embodiments, a heterocyclyl group is a 5-6–membered ring system having ring carbon atoms and 1–4 ring heteroatoms provided in the ring system, wherein each heteroatom is independently selected 25 from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6–membered heterocyclyl has 1–3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5- 6–membered heterocyclyl has 1–2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6–membered heterocyclyl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur. Each instance of a heterocyclyl group may be independently 30 optionally substituted, i.e., unsubstituted (an “unsubstituted heterocyclyl”) or substituted (a “substituted heterocyclyl”) with one or more substituents (e.g., from 1 to 5 substituents, 1 to 4 substituents, 1 to 3 substituents, 1 to 2 substituents, or 1 substituent). In some embodiments, the heterocyclyl group is unsubstituted heterocyclyl. In some embodiments, the heterocyclyl group is substituted heterocyclyl. As used herein, the term “heterocyclylene” refers to a divalent heterocyclyl group. An 5 exemplary 6–membered heterocyclyl group is while an exemplary 6–membered heterocyclylene group is As used herein, the term “hydroxy” refers to the radical –OH. As used herein, the term “hydroxyalkyl” refers to refers to alkyl, as defined above, substituted with one or more (e.g., 1, 2, 3, 4, 5, or 6) hydroxy gourps. Exemplary hydroxyalkyl 10 groups include, but are not limited to, –CH2OH, –CH2CH2OH, and –C(CH3)2OH. As used herein, the term “nitro” refers to –NO2. As used herein, the term “oxo” refers toO, in which both bonds from the oxygen are connected to the same atom. For example, a carbon atom substituted with oxo forms a carbonyl group (–C(O)–). 15 Compounds Compounds of the present disclosure include those described generally herein, and are further illustrated by the classes, subclasses, and species disclosed herein (e.g., compounds of Formula A, Formula B, and Formula C, and subformulas thereof, and compounds of Table 1 and Table 2, and pharmaceutically acceptable salts thereof). 20 Disclosed herein, in some embodiments, is a compound of Formula A: or a pharmaceutically acceptable salt thereof, wherein: each of X1, X2, X3, and X4is independently N or CR1; each of X5and X6is independently N or CR2; 5 each instance of R1is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R1a, C2-20alkenyl optionally substituted with 1-4 instances of R1a, or C2-20alkynyl optionally substituted with 1-4 instances of R1a; each instance of R1ais independently RB; each instance of R2is independently H, RA, C1-20alkyl optionally substituted with 1-4 10 instances of R2a, C2-20alkenyl optionally substituted with 1-4 instances of R2a, or C2-20alkynyl optionally substituted with 1-4 instances of R2a; each instance of R2ais independently RB; R3is C1-6alkyl, C1-6haloalkyl, C3-6carbocyclyl, or 3-6–membered heterocyclyl having 1- 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R3is optionally 15 substituted with 1-6 instances of R3a; each R3ais independently halo, –CN, –NO2, C1-6alkyl, or C1-6alkoxy; each of R4and R5is independently H, halo, –CN, –NO2, C1-6alkyl, C1-6haloalkyl, or C3-6carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3-6carbocyclylene; 20 Ring A is C3-14carbocyclylene or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R6is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R6a, C2-20alkenyl optionally substituted with 1-4 instances of R6a, or C2-20alkynyl optionally substituted with 1-4 instances of R6a; 25 each instance of R6ais independently RB; L0is –O–,–NRL1–, –C(O)–, or –CRL2RL3–; L1is absent, –O–, –NRL1–, –C(O)–, or –CRL2RL3–; L2is absent, –O–, –NRL1–, or –CRL2RL3–; each instance of RL1is independently H or C1-6alkyl; 30 each instance of RL2and RL3is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-6carbocyclyl, or RL2and RL3are taken together with the atom to which each is attached to form C3-6carbocyclylene; R7is Ring B is C6-14aryl or 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R8is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 5 instances of R8a, C2-20alkenyl optionally substituted with 1-4 instances of R8a, or C2-20alkynyl optionally substituted with 1-4 instances of R8a; each instance of R8ais independently RB; Y1is –C(O)– or –CRY1RY2–; each instance of RY1and RY2is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-610 carbocyclyl, or RY1and RY2are taken together with the atom to which each is attached to form C3-6carbocyclylene; Y2is absent or Ring D is C6-14arylene, C3-14carbocyclylene, 5-14–membered heteroarylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered 15 heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R9is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R9a, C2-20alkenyl optionally substituted with 1-4 instances of R9a, or C2-20alkynyl optionally substituted with 1-4 instances of R9a; 20 each instance of R9ais independently RB; Y3is absent, –C(O)–, or –CRY1RY2–; each instance of RY1and RY2is independently H or C1-6alkyl; R10is H, halo, –CN, –NO2, –OH, –NH2, C1-6haloalkyl, C1-20alkyl, C1-20heteroalkyl, C2- 20alkenyl, C2-20alkynyl, or 25 Ring E is C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R11is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R11a, C2-20alkenyl optionally substituted with 1-4 instances of R11a, or C2-20alkynyl optionally substituted with 1-4 instances of R11a; each instance of R11ais independently RB; 5 each instance of RAis independently C1-6haloalkyl, halo, –CN, –NO2, –SF5, –C(O)Raa, – C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, – S(O)2F, –S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, or –SRaa; each instance of RBis independently halo, –CN, –NO2, –SF5, –C(O)Raa, –C(O)ORaa, – C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, –S(O)2F, – 10 S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, –SRaa, or –Si(Raa)3; each instance of Raais independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-20heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 15 each instance of Rbbis independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-20heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; m is 0, 1, 2, 3, 4, 5, or 6; 20 n is 0, 1, 2, 3, 4, 5, or 6; o is 0, 1, 2, 3, 4, 5, or 6; and p is 0, 1, 2, 3, 4, 5, or 6. Disclosed herein, in some embodiments, is a compound of Formula B: or a pharmaceutically acceptable salt thereof, wherein: each of X1, X2, X3, and X4is independently N or CR1; each of X5and X6is independently N or CR2; 5 each instance of R1is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R1a, C2-20alkenyl optionally substituted with 1-4 instances of R1a, or C2-20alkynyl optionally substituted with 1-4 instances of R1a; each instance of R1ais independently RB; each instance of R2is independently H, RA, C1-20alkyl optionally substituted with 1-4 10 instances of R2a, C2-20alkenyl optionally substituted with 1-4 instances of R2a, or C2-20alkynyl optionally substituted with 1-4 instances of R2a; each instance of R2ais independently RB; R3is C1-6alkyl, C1-6haloalkyl, C3-6carbocyclyl, or 3-6–membered heterocyclyl having 1- 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R3is optionally 15 substituted with 1-6 instances of R3a; each R3ais independently halo, –CN, –NO2, C1-6alkyl, or C1-6alkoxy; each of R4and R5is independently H, halo, –CN, –NO2, C1-6alkyl, C1-6haloalkyl, or C3-6carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3-6carbocyclylene; 20 Ring A is C3-14carbocyclylene or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R6is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R6a, C2-20alkenyl optionally substituted with 1-4 instances of R6a, or C2-20alkynyl optionally substituted with 1-4 instances of R6a; 25 each instance of R6ais independently RB; L0is –O–,–NRL1–, –C(O)–, or –CRL2RL3–; L1is absent, –O–, –NRL1–, –C(O)–, or –CRL2RL3–; L2is absent, –O–, –NRL1–, or –CRL2RL3–; each instance of RL1is independently H or C1-6alkyl; 30 each instance of RL2and RL3is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-6carbocyclyl, or RL2and RL3are taken together with the atom to which each is attached to form C3-6carbocyclylene; R7is Ring B is C6-14aryl or 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R8is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 5 instances of R8a, C2-20alkenyl optionally substituted with 1-4 instances of R8a, or C2-20alkynyl optionally substituted with 1-4 instances of R8a; each instance of R8ais independently RB; Y1is –C(O)– or –CRY1RY2–; each instance of RY1and RY2is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-610 carbocyclyl, or RY1and RY2are taken together with the atom to which each is attached to form C3-6carbocyclylene; Y2is absent or Ring D is C6-14arylene, C3-14carbocyclylene, 5-14–membered heteroarylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered 15 heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R9is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R9a, C2-20alkenyl optionally substituted with 1-4 instances of R9a, or C2-20alkynyl optionally substituted with 1-4 instances of R9a; 20 each instance of R9ais independently RB; Y3is absent, –C(O)–, or –CRY1RY2–; each instance of RY1and RY2is independently H or C1-6alkyl; R10is H, halo, –CN, –NO2, –OH, –NH2, C1-6haloalkyl, C1-20alkyl, C1-20heteroalkyl, C2- 20alkenyl, C2-20alkynyl, or 25 Ring E is C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R11is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R11a, C2-20alkenyl optionally substituted with 1-4 instances of R11a, or C2-20alkynyl optionally substituted with 1-4 instances of R11a; each instance of R11ais independently RB; 5 each instance of RAis independently C1-6haloalkyl, halo, –CN, –NO2, –SF5, –C(O)Raa, – C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, – S(O)2F, –S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, or –SRaa; each instance of RBis independently halo, –CN, –NO2, –SF5, –C(O)Raa, –C(O)ORaa, – C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, –S(O)2F, – 10 S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, –SRaa, or –Si(Raa)3; each instance of Raais independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-20heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 15 each instance of Rbbis independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-20heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; m is 0, 1, 2, 3, 4, 5, or 6; 20 n is 0, 1, 2, 3, 4, 5, or 6; o is 0, 1, 2, 3, 4, 5, or 6; and p is 0, 1, 2, 3, 4, 5, or 6. Disclosed herein, in some embodiments, is a compound of Formula C: or a pharmaceutically acceptable salt thereof, an atropisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof, wherein: each of X1, X2, X3, and X4is independently N or CR1; 5 each of X5and X6is independently N or CR2; each instance of R1is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R1a, C2-20alkenyl optionally substituted with 1-4 instances of R1a, or C2-20alkynyl optionally substituted with 1-4 instances of R1a; each instance of R1ais independently RB; 10 each instance of R2is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R2a, C2-20alkenyl optionally substituted with 1-4 instances of R2a, or C2-20alkynyl optionally substituted with 1-4 instances of R2a; each instance of R2ais independently RB; R3is C1-6alkyl, C1-6haloalkyl, C3-6carbocyclyl, or 3-6–membered heterocyclyl having 1- 15 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R3is optionally substituted with 1-6 instances of R3a; each R3ais independently halo, –CN, –NO2, C1-6alkyl, or C1-6alkoxy; each of R4and R5is independently H, halo, –CN, –NO2, C1-6 alkyl, C1-6 haloalkyl, or C3-6 carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form 20 carbonyl or C3-6carbocyclylene; Ring A is C3-14carbocyclylene or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R6is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R6a, C2-20alkenyl optionally substituted with 1-4 instances of R6a, or C2-20alkynyl 25 optionally substituted with 1-4 instances of R6a; each instance of R6ais independently RB; L0is –O–,–NRL1–, –C(O)–, or –CRL2RL3–; L1is absent, –O–, –NRL1–, –C(O)–, or –CRL2RL3–; L2is absent, –O–, –NRL1–, or –CRL2RL3–; 30 each instance of RL1is independently H or C1-6alkyl; each instance of RL2and RL3is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-6carbocyclyl, or RL2and RL3are taken together with the atom to which each is attached to form C3-6carbocyclylene; R7is Ring B is C6-14aryl or 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R8is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 5 instances of R8a, C2-20alkenyl optionally substituted with 1-4 instances of R8a, or C2-20alkynyl optionally substituted with 1-4 instances of R8a; each instance of R8ais independently RB; Y1is –C(O)– or –CRY1RY2–; each instance of RY1and RY2is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-610 carbocyclyl, or RY1and RY2are taken together with the atom to which each is attached to form C3-6carbocyclylene; Y2is absent or Ring D is C6-14arylene, C3-14carbocyclylene, 5-14–membered heteroarylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered 15 heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R9is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R9a, C2-20alkenyl optionally substituted with 1-4 instances of R9a, or C2-20alkynyl optionally substituted with 1-4 instances of R9a; 20 each instance of R9ais independently RB; Y3is absent, –C(O)–, or –CRY1RY2–; each instance of RY1and RY2is independently H or C1-6alkyl; R10is H, halo, –CN, –NO2, –OH, –NH2, C1-6haloalkyl, C1-20alkyl, C1-20heteroalkyl, C2- 20alkenyl, C2-20alkynyl, or 25 Ring E is C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R11is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R11a, C2-20alkenyl optionally substituted with 1-4 instances of R11a, or C2-20alkynyl optionally substituted with 1-4 instances of R11a; each instance of R11ais independently RB; 5 each instance of RAis independently C1-6haloalkyl, halo, –CN, –NO2, –SF5, –C(O)Raa, – C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, – S(O)2F, –S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, or –SRaa; each instance of RBis independently halo, –CN, –NO2, –SF5, –C(O)Raa, –C(O)ORaa, – C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, –S(O)2F, – 10 S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, –SRaa, or –Si(Raa)3; each instance of Raais independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-20heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 15 each instance of Rbbis independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-20heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; m is 0, 1, 2, 3, 4, 5, or 6; 20 n is 0, 1, 2, 3, 4, 5, or 6; o is 0, 1, 2, 3, 4, 5, or 6; and p is 0, 1, 2, 3, 4, 5, or 6. In some embodiments, when each of X1, X2, X3, and X4is CR1; each of X5and X6is CH; R3is each of R4and R5is H; Ring A is L0is –C(O)–; L1is –CH2–; L2is –O–; R7is 25 ; R8is ha1 Y1 Y2 2 3 lo; Y is –CR R –; Y is absent or ; and Y is absent or – CRY1RY2–, then R10is other than H, halo, In some embodiments, when each of X1, X2, X3, and X4is CH; each of X5and X6is CH; R3is each of R4and R5is H; Ring A is L0is –C(O)–; L1is –CH2–; L2is –O–; R7is 5 ; R8is –Cl; Y1is –CH2– or –CF2–; Y2is absent or andY3is absent or –CH2–, then R10is other than H, –F, In some embodiments, the compound is other than the following compounds: an In some embodiments, X1is CR1. In some embodiments, X1is N. In some embodiments, X2is CR1. In some embodiments, X2is N. In some embodiments, X3is CR1. In some embodiments, X3is N. In some embodiments, X4is CR1. In some embodiments, X4is N. 5 In some embodiments, X1is CR1, X2is CR1, X3is CR1, and X4is CR1. In some embodiments, X1is N, X2is CR1, X3is CR1, and X4is CR1. In some embodiments, X1is CR1, X2is N, X3is CR1, and X4is CR1. In some embodiments, X1is CR1, X2is CR1, X3is N, and X4is CR1. In some embodiments, X1is CR1, X2is CR1, X3is CR1, and X4is N. In some embodiments, X1is CH, X2is CH, X3is CH, and X4is CH. In some 10 embodiments, X1is CR1, X2is CH, X3is CH, and X4is CH. In some embodiments, X1is CH, X2is CR1, X3is CH, and X4is CH. In some embodiments, X1is CH, X2is CH, X3is CR1, and X4is CH. In some embodiments, X1is CH, X2is CH, X3is CH, and X4is CR1. In some embodiments, X1is N, X2is CH, X3is CH, and X4is CH. In some embodiments, X1is CH, X2is N, X3is CH, and X4is CH. In some embodiments, X1is CH, X2is 15 CH, X3is N, and X4is CH. In some embodiments, X1is CH, X2is CH, X3is CH, and X4is N. In some embodiments, each instance of R1is independently H, RA, C1-12alkyl optionally substituted with 1-4 instances of R1a, C2-12alkenyl optionally substituted with 1-4 instances of R1a, or C2-12alkynyl optionally substituted with 1-4 instances of R1a. In some embodiments, each instance of R1is independently H, RA, C1-6alkyl optionally 20 substituted with 1-4 instances of R1a, C2-6alkenyl optionally substituted with 1-4 instances of R1a, or C2-6alkynyl optionally substituted with 1-4 instances of R1a. In some embodiments, each instance of R1is independently H, RA, C1-20alkyl, C2-20alkenyl, or C2-20alkynyl. In some embodiments, each instance of R1is independently H, RA, C1-12alkyl, C2-1225 alkenyl, or C2-12alkynyl. 40 In some embodiments, each instance of R1is independently H, RA, C1-6alkyl, C2-6alkenyl, or C2-6alkynyl. In some embodiments, each instance of R1is independently H, RA, or C2-20alkynyl optionally substituted with 1-4 instances of R1a. 5 In some embodiments, each instance of R1is independently H, RA, or C2-12alkynyl optionally substituted with 1-4 instances of R1a. In some embodiments, each instance of R1is independently H, RA, or C2-6alkynyl optionally substituted with 1-4 instances of R1a. In some embodiments, each instance of R1is independently H, halo, –CN, –NO2, – 10 C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, C1-20alkyl, C2-20alkenyl, or C2-20alkynyl. In some embodiments, each instance of R1is independently H, H, halo, –CN, –NO2, – C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, C1-12alkyl, C2-12alkenyl, or C2-12alkynyl. In some embodiments, each instance of R1is independently H, halo, –CN, –NO2, – C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, C1-6alkyl, C2-6alkenyl, or C2-6alkynyl. 15 In some embodiments, each instance of R1is independently H, halo, –CN, –NO2, – C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or C2-20alkynyl optionally substituted with 1-4 instances of R1a. In some embodiments, each instance of R1is independently H, halo, –CN, –NO2, – C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or C2-12alkynyl optionally substituted with 1-4 instances of 20 R1a. In some embodiments, each instance of R1is independently H, halo, –CN, –NO2, – C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or C2-6alkynyl optionally substituted with 1-2 instances of R1a. In some embodiments, each instance of R1is independently H, halo, or C2-20alkynyl optionally substituted with 1-4 instances of R1a. 25 In some embodiments, each instance of R1is independently H, halo, or C2-6alkynyl optionally substituted with 1-2 instances of R1a. In some embodiments, each instance of R1is independently H, halo, –CN, –NO2, – C(O)Raa, –N(Rbb)2, –ORaa, or –SRaa. In some embodiments, each instance of R1is independently H or halo. 30 In some embodiments, each instance of R1is independently H, –F, –Cl, or –Br. In some embodiments, each instance of R1is independently H, –F, or –Cl. In some embodiments, each instance of R1is independently H or –F. In some embodiments, each instance of R1is independently H, –F, –Cl, –Br, – C≡CSi(Raa)3, or –C≡CH. In some embodiments, each instance of R1is independently –C≡CSi(Raa)3or –C≡CH. In some embodiments, each instance of R1is independently H, –F, –Cl, –Br, – C≡CSi(CH3)3, or –C≡CH. In some embodiments, each instance of R1is independently –C≡CSi(CH3)3or –C≡CH. 5 In some embodiments, each instance of R1ais independently halo, –CN, –NO2, –N(Rbb)2, –ORaa, –SRaa, or –Si(Raa)3. In some embodiments, R1ais –Si(Raa)3. In some embodiments, R1ais –Si(CH3)3. In some embodiments, X5is CR5. In some embodiments, X5is N. In some embodiments, X6is CR6. In some embodiments, X6is N. 10 In some embodiments, X5is CR2and X6is CR2. In some embodiments, X5is N and X6is CR2. In some embodiments, X5is CR2and X6is N. In some embodiments, X5is N and X6is N. In some embodiments, X5is CH and X6is CF. In some embodiments, X5is CF and X6is CH. 15 In some embodiments, each instance of R2is independently H, RA, C1-12alkyl optionally substituted with 1-4 instances of R2a, C2-12alkenyl optionally substituted with 1-4 instances of R2a, or C2-12alkynyl optionally substituted with 1-4 instances of R2a. In some embodiments, each instance of R2is independently H, RA, C1-6 alkyl optionally substituted with 1-4 instances of R2a, C2-6alkenyl optionally substituted with 1-4 instances of 20 R2a, or C2-6alkynyl optionally substituted with 1-4 instances of R2a. In some embodiments, each instance of R2is independently H, RA, C1-20alkyl, C2-20alkenyl, or C2-20alkynyl. In some embodiments, each instance of R2is independently H, RA, C1-12alkyl, C2-12alkenyl, or C2-12alkynyl. 25 In some embodiments, each instance of R2is independently H, RA, C1-6alkyl, C2-6alkenyl, or C2-6alkynyl. In some embodiments, each instance of R2is independently H, RA, or C2-20alkynyl optionally substituted with 1-4 instances of R2a. In some embodiments, each instance of R2is independently H, RA, or C2-12alkynyl 30 optionally substituted with 1-4 instances of R2a. In some embodiments, each instance of R2is independently H, RA, or C2-6alkynyl optionally substituted with 1-4 instances of R2a. In some embodiments, each instance of R2is independently H, halo, –CN, –NO2, – C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, C1-20alkyl, C2-20alkenyl, or C2-20alkynyl. In some embodiments, each instance of R2is independently H, H, halo, –CN, –NO2, – C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, C1-12alkyl, C2-12alkenyl, or C2-12alkynyl. In some embodiments, each instance of R2is independently H, halo, –CN, –NO2, – C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, C1-6alkyl, C2-6alkenyl, or C2-6alkynyl. 5 In some embodiments, each instance of R2is independently H, halo, –CN, –NO2, – C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or C2-20alkynyl optionally substituted with 1-4 instances of R2a. In some embodiments, each instance of R2is independently H, halo, –CN, –NO2, – C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or C2-12alkynyl optionally substituted with 1-4 instances of 10 R2a. In some embodiments, each instance of R2is independently H, halo, –CN, –NO2, – C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or C2-6alkynyl optionally substituted with 1-2 instances of R2a. In some embodiments, each instance of R2is independently H, halo, or C2-20alkynyl optionally substituted with 1-4 instances of R2a. 15 In some embodiments, each instance of R2is independently H, halo, or C2-6alkynyl optionally substituted with 1-2 instances of R2a. In some embodiments, each instance of R2is independently H, halo, –CN, –NO2, – C(O)Raa, –N(Rbb)2, –ORaa, or –SRaa. In some embodiments, each instance of R2is independently H or halo. 20 In some embodiments, each instance of R2is independently H, –F, –Cl, or –Br. In some embodiments, each instance of R2is independently H, –F, or –Cl. In some embodiments, each instance of R2is independently H or –F. In some embodiments, R3is C1-6alkyl, wherein R3is optionally substituted with 1-6 instances of R3a. In some embodiments, R3is C1-6haloalkyl, wherein R3is optionally substituted 25 with 1-6 instances of R3a. In some embodiments, R3is C3-6carbocyclyl, wherein R3is optionally substituted with 1-6 instances of R3a. In some embodiments, R3is 3-6–membered heterocyclyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R3is optionally substituted with 1-6 instances of R3a. In some embodiments, R3is 3-6–membered heterocyclyl having 1 heteroatom selected from nitrogen and oxygen, wherein R3is optionally 30 substituted with 1-6 instances of R3a. In some embodiments, R3is C1-6alkyl, C1-6haloalkyl, C3-6carbocyclyl, or 3-6–membered heterocyclyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R3is C1-6alkyl, C1-6haloalkyl, C3-6carbocyclyl, or 3-6–membered heterocyclyl having 1 heteroatom selected from nitrogen and oxygen. In some embodiments, R3 is C1-6alkyl. In some embodiments, R3is C1-6haloalkyl. In some embodiments, R3is C3-6carbocyclyl. In some embodiments, R3is 3-6–membered heterocyclyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R3is 3-6– membered heterocyclyl having 1 heteroatom selected from nitrogen and oxygen. 5 In some embodiments, R3is –Me, –Et, –nPr, –iPr, –nBu, –iBu, –sBu, –tBu, –(CH2)4CH3, –(CH2)5CH6, –CH2F, –CHF2, –CF3, –CH2CF3, –CH(CF3)2, –CF2CF3, –CH(CF3)(CF2OCH3), cyclopropyl, , cyclobutyl, cyclopentyl, cyclohexyl, or In some embodiments, R3is –Me, –Et, –nPr, –iPr, –CH2F, –CHF2, –CF3, –CH2CF3, – CH(CF3)2, –CF2CF3, –CH(CF3)(CF2OCH3), cyclopropyl, , cyclobutyl, or 10 In some embodiments, R3is –Me, –Et, –nPr, –iPr, –CH2F, –CHF2, –CF3, –CH2CF3, – CH(CF3)2, –CF2CF3, –CH(CF3)(CF2OCH3), cyclopropyl, cyclobutyl, or In some embodiments, R3is –nPr, –iPr, –CH2F, –CHF2, –CF3, –CH2CF3, –CH(CF3)2, – CF2CF3, –CH(CF3)(CF2OCH3), cyclopropyl, , cyclobutyl, or In some embodiments, R3is –nPr, –iPr, –CH2CF3, –CH(CF3)2, –CF2CF3, – 15 CH(CF3)(CF2OCH3), cyclopropyl, , cyclobutyl, o In some embodiments, R3is –iPr, –CH2CF3, –CH(CF3)2, –CF2CF3, – CH(CF3)(CF2OCH3), cyclopropyl, , cyclobutyl, or In some embodiments, R3is –iPr, –CH2CF3, or cyclopropyl. In some embodiments, R3is –iPr or –CH2CF3. In some embodiments, R3is –iPr. In some embodiments, R3is –CH2CF3. In 20 some embodiments, R3is cyclopropyl. In some embodiments, each instance of R3ais independently –F, –Cl, –Br, C1-4alkyl, or C1-4alkoxy. In some embodiments, each instance of R3ais independently –F, –Cl, –Br, –Me, –Et, – nPr, –iPr, –nBu, –iBu, –sBu, –tBu, –OMe, –OEt, –OnPr, –OiPr, –OnBu, –OiBu, –OsBu, or – OtBu. In some embodiments, each instance of R3ais independently –F, –Cl, –Me, –Et, –nPr, – 5 iPr, –OMe, –OEt, –OnPr, or –OiPr. In some embodiments, each instance of R3ais independently –F, –Cl, –Me, –Et, –OMe, or –OEt. In some embodiments, each instance of R3ais independently –F, –Me, or –OMe. In some embodiments, R4is H, halo, –CN, –NO2, C1-6alkyl, C1-6haloalkyl, or C3-610 carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3-6carbocyclylene. In some embodiments, R4is H, halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, or C3-6carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3-6carbocyclylene. 15 In some embodiments, R4is H, halo, C1-6alkyl, C1-6haloalkyl, or C3-6carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3-6carbocyclylene. In some embodiments, R4is H, halo, C1-3 alkyl, C1-3 haloalkyl, or C3-4 carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3-420 carbocyclylene. In some embodiments, R4is independently H, –F, –Cl, , –CN, –NO2, –OH, –Me, –Et, – iPr, –tBu, –CF3, –OMe, –OEt, –OiPr, –OtBu, , or R4and R5are taken together with the atom to which each is attached to form carbonyl or cyclopropylene ring. In some embodiments, R4is H, –F, –Cl, –Me, –Et, –CF3, or or R4and R5are 25 taken together with the atom to which each is attached to form carbonyl or cyclopropylene ring. In some embodiments, R4is H, –F, –Me, –CF3, or4 5 or R and R are taken together with the atom to which each is attached to form carbonyl or cyclopropylene ring. In some embodiments, R5is H, halo, –CN, –NO2, C1-6alkyl, C1-6haloalkyl, or C3-6carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form 30 carbonyl or C3-6carbocyclylene. In some embodiments, R5is H, halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, or C3-6carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3-6carbocyclylene. In some embodiments, R5is H, halo, C1-6alkyl, C1-6haloalkyl, or C3-6carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3-6carbocyclylene. In some embodiments, R5is H, halo, C1-3alkyl, C1-3haloalkyl, or C3-4carbocyclyl, or R45 and R5are taken together with the atom to which each is attached to form carbonyl or C3-4carbocyclylene. In some embodiments, R5is independently H, –F, –Cl, , –CN, –NO2, –OH, –Me, –Et, – iPr, –tBu, –CF3, –OMe, –OEt, –OiPr, –OtBu, or R4and R5are taken together with the atom to which each is attached to form carbonyl or cyclopropylene ring. 10 In some embodiments, R5is H, –F, –Cl, –Me, –Et, –CF3, or4 5 or R and R are taken together with the atom to which each is attached to form carbonyl or cyclopropylene ring. In some embodiments, R5is H, –F, –Cl, –Me, –Et, –CF3, or or R4and R5are taken together with the atom to which each is attached to form carbonyl or cyclopropylene ring. In some embodiments, R5is H, –F, –Me, –CF3, or4 5 or R and R are taken together 15 with the atom to which each is attached to form carbonyl or cyclopropylene ring. In some embodiments, R4is H and R5is H, or R4and R5are taken together with the atom to which each is attached to form carbonyl. In some embodiments, R4is H and R5is H. In some embodiments, R4and R5are taken together with the atom to which each is 20 attached to form carbonyl. In some embodiments, Ring A is C3-10carbocyclylene or 3-10–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring A is C3-8carbocyclylene or 3-8–membered heterocyclylene having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. 25 In some embodiments, Ring A is C3-14carbocyclylene. In some embodiments, Ring A is C3-10carbocyclylene. In some embodiments, Ring A is C3-8carbocyclylene. In some embodiments, Ring A is C3-6carbocyclylene. In some embodiments, Ring A is 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, 30 Ring A is 3-10–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring A is 3-8–membered heterocyclylene having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring A is 5-10–membered heterocyclylene having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring A is 3-5–membered heterocyclylene having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring A is 6–membered heterocyclylene having 1-4 heteroatoms 5 independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring A is 7- 10–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring A is monocyclic. In some embodiments, Ring A is polycyclic. In some embodiments, Ring A is a spirocyclic or bridged ring system. In some 10 embodiments, Ring A is a spirocyclic ring system. In some embodiments, Ring A is a bridged ring system. In some embodiments, Ring A is a fused ring system. In some embodiments, Ring A is saturated. In some embodiments, Ring A is partially unsaturated. In some embodiments, Ring A together with its R6substituents is selected from: 15

[0002] In some embodiments, Ring A together with its R6substituents is selected from: 5 In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is . In some embodiments, Ring A together with its R6substituents is . In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together 5 with its R6substituents is6 . In some embodiments, Ring A together with its R substituents is . In some embod6 iments, Ring A together with its R substituents is . In some embodiments, Ring A t6 ogether with its R substituents is . In some embodiments, Ring A together with it6 s R substituents is In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A toge6 ther with its R substituents is . In6 some embodiments, Ring A together with its R substituents is In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is 5 In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is . In some embodiments, Ring A together with its R6substituents is . In some embodiments, Ring A toge6 ther with its R substituents is 5 In some embodiments, R6 ing A together with its R substituents is In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is . In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is selected from: 5 In some embodiments, Ring A together with its R6substituents is . In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is 10I b di Ri A h i h i R6b i isIn some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is . In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is In some 5 embodiments, Ring A together with its R6substituents is . In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6substituents is In some embodiments, Ring A together with its R6 substituents is In some embodiments, each instance of R6is independently oxo, RA, C1-12alkyl optionally substituted with 1-4 instances of R6a, C2-12alkenyl optionally substituted with 1-4 5 instances of R6a, or C2-12alkynyl optionally substituted with 1-4 instances of R6a. In some embodiments, each instance of R6is independently oxo, RA, C1-6alkyl optionally substituted with 1-4 instances of R6a, C2-6alkenyl optionally substituted with 1-4 instances of R6a, or C2-6alkynyl optionally substituted with 1-4 instances of R6a. In some embodiments, each instance of R6is independently oxo, RA, C1-20alkyl, C2-2010 alkenyl, or C2-20alkynyl. In some embodiments, each instance of R6is independently oxo, RAor C1-20alkyl optionally substituted with 1-4 instances of R6a. In some embodiments, each instance of R6is independently oxo, C1-6haloalkyl, halo, – CN, –NO2, –C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or C1-20alkyl optionally substituted with 1-4 15 instances of R6a. In some embodiments, each instance of R6is independently oxo, C1-6haloalkyl, halo, – CN, –NO2, –C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or C1-20alkyl optionally substituted with 1-4 instances of R6a. In some embodiments, each instance of R6is independently oxo, C1-6haloalkyl, halo, – 20 CN, –NO2, –C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or C1-20alkyl optionally substituted with 1-4 instances of R6a. In some embodiments, each instance of R6is independently oxo, C1-6 haloalkyl, halo, – ORaa, or C1-20alkyl optionally substituted with 1-4 instances of R6a. In some embodiments, each instance of R6is independently C1-6haloalkyl, halo, –ORaa, 25 or C1-20alkyl optionally substituted with 1-4 instances of R6a. In some embodiments, each instance of R6is independently –CH2F, –CHF2, –CF3, – CH2CF3, –CH(CF3)2, –CF2CF3, –F, –Cl, –Br, –OH, –OMe, –OEt, –OiPr, –OtBu, –Me, –Et, –nPr, –iPr –nBu –iBu –sBu –tBu –(CH2)4CH3or –(CH2)5CH6 In some embodiments, each instance of R6is independently –CH2F, –CHF2, –CF3, – CH2CF3, –CH(CF3)2, –CF2CF3, –OH, –OMe, –OEt, –OiPr, –OtBu, –Me, –Et, –nPr, –iPr, –nBu, – iBu, –sBu, or –tBu. In some embodiments, each instance of R6is independently –CH2F, –CHF2, –CF3, – 5 CH2CF3, –CH(CF3)2, –CF2CF3, –OH, –OMe, –OEt, –OiPr, –OtBu, –Me, –Et, –nPr, –iPr, or –tBu. In some embodiments, each instance of R6is independently –CH2F, –CHF2, –CF3, – CH2CF3, –CH(CF3)2, –CF2CF3, –OH, –OMe, –OEt, –Me, or –Et. In some embodiments, each instance of R6is independently –CH2F, –CHF2,–CF3, –OH, or –Me. 10 In some embodiments, each instance of R6is independently –CHF2, –OH, or –Me. In some embodiments, L0is –O–. In some embodiments, L0is –NRL1–. In some embodiments, L0is –C(O)–. In some embodiments, L0is –CRL2RL3–. In some embodiments, L0is –NRL1– or –CRL2RL3–. In some embodiments, L0is –NH–, –NCH3–, –CH2–, or –CH(CH3)–. In some 15 embodiments, L0is –NH– or –NCH3–. In some embodiments, L0is –CH2– or –CH(CH3)–. In some embodiments, L0is –NH–. In some embodiments, L0is –NCH3–. In some embodiments, L0is –CH2–. In some embodiments, L0is –CH(CH3)–. In some embodiments, L1is absent. In some embodiments, L1is –O–. In some embodiments, L1is –NRL1–. In some embodiments, L1is –C(O)–. In some embodiments, L1is 20 –CRL2RL3–. In some embodiments, L1is –NRL1– or –CRL2RL3–. In some embodiments, L1is –NH–, –NCH3–, –C(O)–, –CH2–, or –CH(CH3)–. In some embodiments, L1is –NH–, –NCH3–, –CH2–, or –CH(CH3)–. In some embodiments, L1is –NH– or –NCH3–. In some embodiments, L1is –CH2– or –CH(CH3)–. In some embodiments, L1is – 25 NH–. In some embodiments, L1is –NCH3–. In some embodiments, L1is –CH2–. In some embodiments, L1is –CH(CH3)–. In some embodiments, L2is absent. In some embodiments, L2is –O–. In some embodiments, L2is –NRL1–. In some embodiments, L2is –CRL2RL3–. In some embodiments, L2is –O– or –CRL2RL3–. 30 In some embodiments, L2is –O–, –CH2–, or –CH(CH3)–. In some embodiments, L2is – O–. In some embodiments, L2is –CH2– or –CH(CH3)–. In some embodiments, L2is –CH2–. In some embodiments, L2is –CH(CH3)–. In some embodiments, each instance of RL1is independently H, –Me, –Et, –nPr, –iPr, – In some embodiments, each instance of RL1is independently H, –Me, –Et, or –iPr. In some embodiments, each instance of RL1is independently H or –Me. In some embodiments, RL2is H, –F, –Cl, –Br, –Me, –Et, –nPr, –iPr, –nBu, –iBu, –sBu, – tBu, –(CH2)4CH3, –(CH2)5CH6, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, or RL2and 5 RL3are taken together to form cyclopropylene, cyclobutylene, cyclopentylene, or cyclohexylene. In some embodiments, RL2is H, –F, –Cl, –Me, –Et, –iPr, cyclopropyl, or cyclobutylene, or RL2and RL3are taken together to form cyclopropylene or cyclobutylene. In some embodiments, RL2is H,–Me, or cyclopropyl, or RL2and RL3are taken together to form cyclopropylene. 10 In some embodiments, RL2is H or –Me. In some embodiments, RL3is H, –F, –Cl, –Br, –Me, –Et, –nPr, –iPr, –nBu, –iBu, –sBu, – tBu, –(CH2)4CH3, –(CH2)5CH6, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, or RL3and RL3are taken together to form cyclopropylene, cyclobutylene, cyclopentylene, or cyclohexylene. In some embodiments, RL3is H, –F, –Cl, –Me, –Et, –iPr, cyclopropyl, or cyclobutylene, 15 or RL3and RL3are taken together to form cyclopropylene or cyclobutylene. In some embodiments, RL3is H,–Me, or cyclopropyl, or RL3and RL3are taken together to form cyclopropylene. In some embodiments, RL3is H or –Me. In some embodiments, RL2is H and RL3is H. In some embodiments, RL2is H and RL3is 20 –Me. In some embodiments, Ring B is C6-14aryl. In some embodiments, Ring B is C6-10aryl. In some embodiments, Ring B is C6aryl. In some embodiments, Ring B is 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring B is 5-25 14–membered heteroaryl having 1-6 nitrogen atoms. In some embodiments, Ring B is 5-10– membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring B is 5-10–membered heteroaryl having 1-4 nitrogen atoms. In some embodiments, Ring B is 5-6–membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring B is 5-6– 30 membered heteroaryl having 1-4 nitrogen atoms. In some embodiments, Ring B is 5–membered heteroaryl having 1-4 nitrogen atoms. In some embodiments, Ring B is 6–membered heteroaryl having 1-4 nitrogen atoms. In some embodiments, Ring B is monocyclic. In some embodiments, Ring B is polycyclic. In some embodiments, Ring B is completely aromatic. In some embodiments, R7is selected from: 5 In some embodiments, R7is . In some embodiments, R7is In some embodiments, R7is In some embodiments, R7is In some embodiments, R7isIn some embodiments, R7is In some embodiments, R7isIn some embodiments, R7is In some embodiments, R7isIn some embodiments, R7is 10 In some embodiments, R7is In some embodiments, R7is selected from: In some embodiments, R7is . I7 n some embodiments, R is In some embodiments, R7isIn some embodiments, R7is In someN embodiments, R7is8 . In some embodiments, R7is In someembodiments, R7is7 In some embodiments, R is . In some5embodiments, R7is7 . In some embodiments, R isIn some embodiments, R7is R8. In some embodiments, R7is selected from: 10 In some embodiments, R7is I7 n some embodiments, R is . Insome embodiments, R7is In so7 me embodiments, R is . In some embodiments, R7isIn some embodiments, R7is In someembodiments, R7is In some embodiments, each instance of R8is independently oxo, RA, C1-12alkyl optionally substituted with 1-4 instances of R8a, C2-12alkenyl optionally substituted with 1-4 5 instances of R8a, or C2-12alkynyl optionally substituted with 1-4 instances of R8a. In some embodiments, each instance of R8is independently oxo, RA, C1-6alkyl optionally substituted with 1-4 instances of R8a, C2-6alkenyl optionally substituted with 1-4 instances of R8a, or C2-6alkynyl optionally substituted with 1-4 instances of R8a. In some embodiments, each instance of R8is independently oxo, RA, or C1-20alkyl 10 optionally substituted with 1-4 instances of R8a. In some embodiments, each instance of R8is independently oxo, C1-6haloalkyl, halo, – CN, –NO2, –C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or C1-20alkyl optionally substituted with 1-4 instances of R8a. In some embodiments, each instance of R8is independently oxo, C1-6haloalkyl, halo, – 15 CN, –NO2, –C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or C1-20alkyl. In some embodiments, each instance of R8is independently oxo, C1-6haloalkyl, halo, – CN, –NO2, or C1-6alkyl. In some embodiments, each instance of R8is independently oxo, –CH2F, –CHF2, –CF3, – CH2CF3, –CH(CF3)2, –CF2CF3, –F, –Cl, –Br, –CN, –NO2, –Me, –Et, –nPr, –iPr, –nBu, –iBu, – 20 sBu, –tBu, –(CH2)4CH3, –(CH2)5CH6, In some embodiments, each instance of R8is independently oxo, –CH2F, –CHF2, –CF3, – CH2CF3, –CH(CF3)2, –CF2CF3, –F, –Cl, –CN, –NO2, –Me, or –Et. In some embodiments, each instance of R8is independently oxo, –CH2F, –CHF2, –CF3, – F, –Cl, –CN, –NO2, or –Me. 25 In some embodiments, each instance of R8is independently oxo, –CF3, –Cl, or –CN. In some embodiments, Y1is –C(O)–. In some embodiments, Y1is –CRY1RY2–. In some embodiments, Y1is –C(O)–, –CH2–, or –CH(CH3)–. In some embodiments, Y1is –C(O)–. In some embodiments, Y1is –CH2–. In some embodiments, Y1is –CH(CH3)–. In some embodiments, Y3is absent. In some embodiments, Y3is –C(O)–. In some embodiments, Y3is –CRY1RY2–. In some embodiments, Y3is absent, –CH2–, or –CH(CH3)–. In some embodiments, Y3is –CH2– or –CH(CH3)–. In some embodiments, Y3is –CH2–. 5 In some embodiments, RY1is H, –F, –Cl, –Br, –Me, –Et, –nPr, –iPr, –nBu, –iBu, –sBu, – tBu, –(CH2)4CH3, –(CH2)5CH6, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, or RY1and RY2are taken together with the atom to which each is attached to form carbonyl, cyclopropylene, cyclobutylene, cyclopentylene, or cyclohexylene. In some embodiments, RY1is H, –F, –Cl, –Me, –Et, –iPr, cyclopropyl, or cyclobutylene, 10 or RY1and RY2are taken together with the atom to which each is attached to form carbonyl, cyclopropylene, or cyclobutylene. In some embodiments, RY1is H,–Me, or cyclopropyl, or RY1and RY2are taken together with the atom to which each is attached to form carbonyl or cyclopropylene. In some embodiments, RY1is H or –Me. 15 In some embodiments, RY2is H, –F, –Cl, –Br, –Me, –Et, –nPr, –iPr, –nBu, –iBu, –sBu, – tBu, –(CH2)4CH3, –(CH2)5CH6, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, or RY2and RY2are taken together with the atom to which each is attached to form carbonyl, cyclopropylene, cyclobutylene, cyclopentylene, or cyclohexylene. In some embodiments, RY2is H, –F, –Cl, –Me, –Et, –iPr, cyclopropyl, or cyclobutylene, 20 or RY2and RY2are taken together with the atom to which each is attached to form carbonyl, cyclopropylene, or cyclobutylene. In some embodiments, RY2is H,–Me, or cyclopropyl, or RY1and RY2a are taken together with the atom to which each is attached to form carbonyl or cyclopropylene. In some embodiments, RY2is H or –Me. 25 In some embodiments, RY1is H and RY2is H. In some embodiments, RY1is H and RY2is –Me. In some embodiments, Y2is absent. In some embodiments, Y2is In some embodiments, Ring D is C - ar 6 14 ylene, C3-14 carbocyclylene, 5-14–membered heteroarylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 30 or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring D is C6-10arylene, C3-10carbocyclylene, 5-10–membered heteroarylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-10–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. 5 In some embodiments, Ring D is C6arylene, C3-8carbocyclylene, 5-6–membered heteroarylene having 1-4 heteroatoms independently selected from nitrogen and oxygen, or 3-8– membered heterocyclylene having 1-4 heteroatoms independently selected from nitrogen and oxygen. In some embodiments, Ring D is C6arylene or 5-6–membered heteroarylene having 1-4 10 heteroatoms independently selected from nitrogen and oxygen. In some embodiments, Ring D is C3-8carbocyclylene or 3-8–membered heterocyclylene having 1-4 heteroatoms independently selected from nitrogen and oxygen. In some embodiments, Ring D is 3-8–membered heterocyclylene having 1-4 heteroatoms independently selected from nitrogen and oxygen. In some embodiments, Ring D is 5– 15 membered heterocyclylene having 1-4 heteroatoms independently selected from nitrogen and oxygen. In some embodiments, Ring D is 6–membered heterocyclylene having 1-4 heteroatoms independently selected from nitrogen and oxygen. In some embodiments, Ring D together with its R9substituents is . In some embodiments, Ring D together with its R9substituents is 20 In some embodiments, each instance of R9is independently oxo, RA, C1-12alkyl optionally substituted with 1-4 instances of R9a, C2-12alkenyl optionally substituted with 1-4 instances of R9a, or C2-12alkynyl optionally substituted with 1-4 instances of R9a. In some embodiments, each instance of R9is independently oxo, RA, C1-6alkyl optionally substituted with 1-4 instances of R9a, C2-6alkenyl optionally substituted with 1-4 instances of 25 R9a, or C2-6alkynyl optionally substituted with 1-4 instances of R9a. In some embodiments, each instance of R9is independently oxo, RA, or C1-20 alkyl optionally substituted with 1-4 instances of R9a. In some embodiments, each instance of R9is independently oxo, C1-6haloalkyl, halo, – CN, –NO2, –C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or C1-20alkyl optionally substituted with 1-4 30 instances of R9a. In some embodiments, each instance of R9is independently oxo, C1-6haloalkyl, halo, – CN, –NO2, –C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or C1-12alkyl optionally substituted with 1-4 instances of R9a. In some embodiments, each instance of R9is independently oxo, C1-6haloalkyl, halo, – 5 CN, –NO2, –C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or C1-6alkyl optionally substituted with 1-4 instances of R9a. In some embodiments, each instance of R9is independently oxo, C1-6haloalkyl, halo, – ORaa, or C1-20alkyl optionally substituted with 1-4 instances of R9a. In some embodiments, each instance of R9is independently C1-6haloalkyl, halo, –ORaa, 10 or C1-20alkyl optionally substituted with 1-4 instances of R9a. In some embodiments, each instance of R9is independently –CH2F, –CHF2, –CF3, – CH2CF3, –CH(CF3)2, –CF2CF3, –F, –Cl, –Br, –OH, –OMe, –OEt, –OiPr, –OtBu, –Me, –Et, –nPr, –iPr, –nBu, –iBu, –sBu, –tBu, –(CH2)4CH3, or –(CH2)5CH6. In some embodiments, each instance of R9is independently –CH2F, –CHF2, –CF3, –15 CH2CF3, –CH(CF3)2, –CF2CF3, –OH, –OMe, –OEt, –OiPr, –OtBu, –Me, –Et, –nPr, –iPr, –nBu, – iBu, –sBu, or –tBu. In some embodiments, each instance of R9is independently –CH2F, –CHF2, –CF3, – CH2CF3, –CH(CF3)2, –CF2CF3, –OH, –OMe, –OEt, –OiPr, –OtBu, –Me, –Et, –nPr, –iPr, or –tBu. In some embodiments, each instance of R9is independently –CH2F, –CHF2, –CF3, – 20 CH2CF3, –CH(CF3)2, –CF2CF3, –OH, –OMe, –OEt, –Me, or –Et. In some embodiments, each instance of R9is independently –CH2F, –CHF2,–CF3, –OH, or –Me. In some embodiments, each instance of R9is independently –CHF2, –OH, or –Me. In some embodiments, R10is H, halo, –CN, –NO2, –OH, –NH2, C1-6haloalkyl, C1-2025 alkyl, C1-20heteroalkyl, C2-20alkenyl, or C2-20alkynyl. In some embodiments, R10is H, halo, –CN, –NO2, –OH, –NH2, C1-6haloalkyl, C1-20alkyl, C1-12heteroalkyl, C2-12alkenyl, or C2-12alkynyl. In some embodiments, R10is H, halo, –CN, –NO2, –OH, –NH2, C1-6 haloalkyl, C1-6 alkyl, C1-6heteroalkyl, C2-6alkenyl, or C2-6alkynyl. 30 In some embodiments, R10is H, –F, or –OH. In some embodiments, R10is H or –F. In some embodiments, R10is H. In some embodiments, R10is –F. In some embodiments, R10is – OH. In some embodiments, R10is In some embodiments, Ring E is C6-10aryl, C3-10carbocyclyl, 5-10–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-10– membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, 5 and sulfur. In some embodiments, Ring E is C6-8aryl, C3-10carbocyclyl, 5-8–membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-8–membered heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring E is C6-10aryl or 5-10–membered heteroaryl having 1-6 10 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring E is C6-8aryl or 5-8–membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring E is C3-10carbocyclyl or 3-10–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some 15 embodiments, Ring E is C3-10carbocyclyl or 3-8–membered heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring E is C6-14aryl. In some embodiments, Ring E is C6-10aryl. In some embodiments, Ring E is C6aryl. In some embodiments, the aryl is completely aromatic. In some embodiments, Ring E is C3-14carbocyclyl. In some embodiments, Ring E is C3- 2010carbocyclyl. In some embodiments, Ring E is C3-8carbocyclyl. In some embodiments, Ring E is 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring E is 5- 10–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring E is 5-8–membered heteroaryl having 1-4 heteroatoms25 independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring E is 5-8– membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen and oxygen. In some embodiments, the heteroaryl is completely aromatic. In some embodiments, Ring E is 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring E is 3- 30 10–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring E is 3-8–membered heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring E is 3-8–membered heterocyclyl having 1-4 heteroatoms independently selected from nitrogen and oxygen. In some embodiments, Ring E is C6-10aryl, C3-10carbocyclyl, 5-10–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-10– 5 membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring E is C6aryl, C3-8carbocyclyl, 5-8–membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-8– membered heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, 10 and sulfur. In some embodiments, Ring E is C6aryl, C3-8carbocyclyl, 5-8–membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen and oxygen, or 3-8–membered heterocyclyl having 1-4 heteroatoms independently selected from nitrogen and oxygen. In some embodiments, Ring E is monocyclic. In some embodiments, Ring E is 15 polycyclic. In some embodiments, Ring E is a spirocyclic or bridged ring system. In some embodiments, Ring E is a spirocyclic ring system. In some embodiments, Ring E is a bridged ring system. In some embodiments, Ring E is a fused ring system. In some embodiments, Ring E is saturated. In some embodiments, Ring E is partially 20 unsaturated. In some embodiments, R10is selected from: or In some embodiments, R10is . In some embodiments, R10is In some embodiments, R10is10 In some embodiments, R is 5 In some embodiments, R10is . In so10 me embodiments, R is In some embodiments, R10is10 In some embodiments, R is In some embodiments, R10is . In some10 embodiments, R is . In some embodiments, R10is . In some embodiments, R10is In some embodiments, R10is In some e10 mbodiments, R is 10 In some embod10 10 iments, R i In some embodiments, R is . In some embodiments, R10is. In som10 e embodiments, R is . In some embodim10 ents, R is In some embodiments, R10is In some embodiments, R10is . In some embodiments, R10is In some embodiments, R10 is In some embodiments, R10is In some embo10 diments, R is In some embodiments, R10is In some embodiments, R10is selected from: 5 10 In some embodiments, R10is In some embo10 diments, R is In some embodiments, R10is10 In some embodiments, R is In some embodiments, R10is In some embodiments,10 10 R is In some embodiments, R is In some embodiments, R10is In some embodiments, R10 is In 5 some embodiments, R10is In so10 me embodiments, R is In some embodiments, R10is In some embodiments, R10is In some embodiments, R10is In some embodi10 10 ments, R is In some embodiments, R is . In some embodiments, R10is In some embodim10 ents, R is In some embodiments, R10is10 . In some embodiments, R is10 . In some embodiments, R10is10 . In some embodiments, R iIn some embodiments, R10is. In some embodiments, R10is In some10 embodiments, R is In some embodiments, R10is In some embodiments, R10is In some embodiments, R10is In some embodiments, R10is In someembodiments, R10is10 In some embodiments, R is 5 In some embodiments, each instance of R11is independently oxo, RA, C1-12alkyl optionally substituted with 1-4 instances of R11a, C2-12alkenyl optionally substituted with 1-4 instances of R11a, or C2-12alkynyl optionally substituted with 1-4 instances of R11a. In some embodiments, each instance of R11is independently oxo, RA, C1-6alkyl optionally substituted with 1-4 instances of R11a, C2-6alkenyl optionally substituted with 1-4 10 instances of R11a, or C2-6 alkynyl optionally substituted with 1-4 instances of R11a. In some embodiments, each instance of R11is independently oxo, RA, or C1-20alkyl optionally substituted with 1-4 instances of R11a. In some embodiments, each instance of R11is independently oxo, C1-6haloalkyl, halo, – CN, –NO2, –C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or C1-20alkyl optionally substituted with 1-4 15 instances of R11a. In some embodiments, each instance of R11is independently oxo, C1-6haloalkyl, halo, – ORaa, –C(O)Raa, or C1-20alkyl optionally substituted with 1-4 instances of R11a. In some embodiments, each instance of R11is independently C1-6haloalkyl, halo, –ORaa, –C(O)Raa, or C1-20alkyl optionally substituted with 1-4 instances of R11a. 20 In some embodiments, each instance of R11is independently –CH2F, –CHF2, –CF3, – CH2CF3, –CH(CF3)2, –CF2CF3, –F, –Cl, –Br, –OH, –OMe, –OEt, –OiPr, –OtBu, –C(O)(CH2)0-18(CH3), –C(O)(CH2)1-8(C=C)(CH2)1-8CH3, –Me, –Et, –nPr, –iPr, –nBu, –iBu, –sBu, –tBu, – (CH2)4CH3, or –(CH2)5CH6. In some embodiments, each instance of R11is independently –CH2F, –CHF2, –CF3, –25 CH2CF3, –CH(CF3)2, –CF2CF3, –OH, –OMe, –OEt, –OiPr, –OtBu, –C(O)(CH2)0-18(CH3), – C(O)(CH2)1 8(C=C)(CH2)1 8CH3–Me –Et –nPr –iPr –nBu –iBu –sBu or –tBu In some embodiments, each instance of R11is independently –CH2F, –CHF2, –CF3, – CH2CF3, –CH(CF3)2, –CF2CF3, –OH, –OMe, –OEt, –OiPr, –OtBu, –C(O)(CH2)0-18(CH3), – C(O)(CH2)1-8(C=C)(CH2)1-8CH3, –Me, –Et, –nPr, –iPr, or –tBu. In some embodiments, each instance of R11is independently –CH2F, –CHF2, –CF3, – 5 CH2CF3, –CH(CF3)2, –CF2CF3, –OH, –OMe, –OEt, –C(O)(CH2)0-18(CH3), –C(O)(CH2)1-8(C=C)(CH2)1-8CH3, –Me, or –Et. In some embodiments, each instance of R11is independently –CH2F, –CHF2,–CF3, –OH, –Me, –C(O)(CH2)0-18(CH3), or –C(O)(CH2)1-8(C=C)(CH2)1-8CH3. In some embodiments, each instance of R11is independently –CH2F, –CHF2,–CF3, –OH, 10 –Me, or –C(O)CH3. In some embodiments, each instance of R11is independently –C(O)(CH2)0-18(CH3), or – C(O)(CH2)1-8(C=C)(CH2)1-8CH3. In some embodiments, each instance of RAis independently C1-6haloalkyl, halo, –CN, – NO2, –SF5, –C(O)Raa, –C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, – 15 S(O)ORaa, –S(O)N(Rbb)2, –S(O)2F, –S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, or –SRaa. In some embodiments, each instance of RAis independently C1-6haloalkyl, halo, –CN, – NO2, –C(O)Raa, –C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, –S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, or –SRaa. 20 In some embodiments, each instance of RAis independently C1-6haloalkyl, halo, –CN, – NO2, –C(O)Raa, –C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –N(Rbb)2, –ORaa, or – SRaa. In some embodiments, each instance of RAis independently C1-6haloalkyl, halo, –CN, – NO2, –C(O)Raa, –C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –N(Rbb)2, –ORaa, or –SRaa. 25 In some embodiments, each instance of RAis independently C1-6haloalkyl, halo, –CN, – NO2, –C(O)Raa, –C(O)ORaa, –C(O)N(Rbb)2, or –C(O)NRbbORbb. In some embodiments, each instance of RAis independently C1-6haloalkyl, halo, –CN, – NO2, –C(O)Raa, –N(Rbb)2, –ORaa, or –SRaa. In some embodiments, each instance of RAis independently C1-6haloalkyl, halo, –CN, – 30 NO2, –C(O)Raa, –N(Rbb)2, or –ORaa. In some embodiments, each instance of RAis independently C1-6haloalkyl, halo, –CN, or –NO2. In some embodiments, each instance of RBis independently halo, –CN, –NO2, –SF5, – C(O)Raa, –C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, – S(O)N(Rbb)2, –S(O)2F, –S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, –SRaa, or – Si(Raa)3. In some embodiments, each instance of RBis independently halo, –CN, –NO2, –C(O)Raa, –C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, – 5 S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, –SRaa, or –Si(Raa)3. In some embodiments, each instance of RBis independently halo, –CN, –NO2, –C(O)Raa, –C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –N(Rbb)2, –ORaa, –SRaa, or –Si(Raa)3. In some embodiments, each instance of RBis independently halo, –CN, –NO2, –C(O)Raa, –C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –N(Rbb)2, –ORaa, –SRaa, or –Si(Raa)3. 10 In some embodiments, each instance of RBis independently halo, –CN, –NO2, –C(O)Raa, –C(O)ORaa, –C(O)N(Rbb)2, or –C(O)NRbbORbb. In some embodiments, each instance of RBis independently halo, –CN, –NO2, –C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or –Si(Raa)3. In some embodiments, each instance of RBis independently halo, –CN, –NO2, –C(O)Raa, 15 –N(Rbb)2, or –ORaa. In some embodiments, each instance of RBis independently halo, –CN, or –NO2. In some embodiments, each instance of Raais independently H, C1-12alkyl, C2-12alkenyl, C2-12alkynyl, C1-12heteroalkyl, C6-10aryl, C3-10carbocyclyl, 5-10–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-10–membered 20 heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, each instance of Raais independently H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6heteroalkyl, C6aryl, C3-8carbocyclyl, 5-8–membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-8–membered heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. 25 In some embodiments, each instance of Raais independently H, C1-20alkyl, or C2-20alkenyl. In some embodiments, each instance of Raais independently H, C1-12alkyl, or C2-12alkenyl. In some embodiments, each instance of Raais independently H, C1-6alkyl, or C2-6alkenyl. In some embodiments, each instance of Raais independently H or C1-6alkyl. In some 30 embodiments, each instance of Raais independently H, –Me, –Et, –nPr, –iPr, –nBu, –iBu, –sBu, –tBu, –(CH2)4CH3, or –(CH2)5CH6. In some embodiments, each instance of Raais independently –Me, –Et, –iPr, –Ph, or In some embodiments, each instance of Rbbis independently H, C1-12alkyl, C2-12alkenyl, C2-12alkynyl, C1-12heteroalkyl, C6-10aryl, C3-10carbocyclyl, 5-10–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-10–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. 5 In some embodiments, each instance of Rbbis independently H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6heteroalkyl, C6aryl, C3-8carbocyclyl, 5-8–membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-8–membered heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, each instance of Rbbis independently H, C1-20alkyl, or C2-2010 alkenyl. In some embodiments, each instance of Rbbis independently H, C1-12alkyl, or C2-12alkenyl. In some embodiments, each instance of Rbbis independently H, C1-6alkyl, or C2-6alkenyl. In some embodiments, each instance of Rbbis independently H or C1-6alkyl. In some embodiments, each instance of Rbbis independently H, –Me, –Et, –nPr, –iPr, –nBu, –iBu, –sBu, 15 –tBu, –(CH2)4CH3, or –(CH2)5CH6. In some embodiments, each instance of Rbbis independently –Me, –Et, –iPr, –Ph, or In some embodiments, m is 0, 1, 2, or 3. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. 20 In some embodiments, n is 0, 1, 2, or 3. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, o is 0, 1, 2, or 3. In some embodiments, o is 0. In some embodiments, o is 1. In some embodiments, o is 2. In some embodiments, o is 3. In some embodiments, p is 0, 1, 2, or 3. In some embodiments, p is 0. In some 25 embodiments, p is 1. In some embodiments, p is 2. In some embodiments, p is 3. In some embodiments of any of the embodiments described above, C1-20alkyl optionally substituted is C1-18alkyl optionally substituted. In some embodiments of any of the embodiments described above, C1-20alkyl optionally substituted is C1-16alkyl optionally substituted. In some embodiments of any of the embodiments described above, C1-20alkyl 30 optionally substituted is C1-14alkyl optionally substituted. In some embodiments of any of the embodiments described above, C1-20alkyl optionally substituted is C1-12alkyl optionally substituted. In some embodiments of any of the embodiments described above, C1-20alkyl optionally substituted is C1-10alkyl optionally substituted. In some embodiments of any of the embodiments described above, C1-20alkyl optionally substituted is C1-8alkyl optionally substituted. In some embodiments of any of the embodiments described above, C1-20alkyl optionally substituted is C1-6alkyl optionally substituted. In some embodiments of any of the embodiments described above, C1-20alkyl optionally substituted is C1-4alkyl optionally 5 substituted. In some embodiments of any of the embodiments described above, C1-20alkyl optionally substituted is C1-3alkyl optionally substituted. In some embodiments of any of the embodiments described above, C2-20alkenyl optionally substituted is C2-18alkenyl optionally substituted. In some embodiments of any of the embodiments described above, C2-20alkenyl optionally substituted is C2-16alkenyl optionally 10 substituted. In some embodiments of any of the embodiments described above, C2-20alkenyl optionally substituted is C2-14alkenyl optionally substituted. In some embodiments of any of the embodiments described above, C2-20alkenyl optionally substituted is C2-12alkenyl optionally substituted. In some embodiments of any of the embodiments described above, C2-20alkenyl optionally substituted is C2-10alkenyl optionally substituted. In some embodiments of any of the 15 embodiments described above, C2-20alkenyl optionally substituted is C2-8alkenyl optionally substituted. In some embodiments of any of the embodiments described above, C2-20alkenyl optionally substituted is C2-6alkenyl optionally substituted. In some embodiments of any of the embodiments described above, C2-20 alkenyl optionally substituted is C2-4 alkenyl optionally substituted. In some embodiments of any of the embodiments described above, C2-20alkenyl 20 optionally substituted is C2-3alkenyl optionally substituted. In some embodiments of any of the embodiments described above, C2-20alkynyl optionally substituted is C2-18alkynyl optionally substituted. In some embodiments of any of the embodiments described above, C2-20alkynyl optionally substituted is C2-16alkynyl optionally substituted. In some embodiments of any of the embodiments described above, C2-20alkynyl 25 optionally substituted is C2-14alkynyl optionally substituted. In some embodiments of any of the embodiments described above, C2-20alkynyl optionally substituted is C2-12alkynyl optionally substituted. In some embodiments of any of the embodiments described above, C2-20alkynyl optionally substituted is C2-10 alkynyl optionally substituted. In some embodiments of any of the embodiments described above, C2-20alkynyl optionally substituted is C2-8alkynyl optionally 30 substituted. In some embodiments of any of the embodiments described above, C2-20alkynyl optionally substituted is C2-6alkynyl optionally substituted. In some embodiments of any of the embodiments described above, C2-20alkynyl optionally substituted is C2-4alkynyl optionally substituted. In some embodiments of any of the embodiments described above, C2-20alkynyl optionally substituted is C2-3alkynyl optionally substituted. In some embodiments of any of the embodiments described above, C1-20alkyl is C1-18alkyl. In some embodiments of any of the embodiments described above, C1-20alkyl is C1-16alkyl. In some embodiments of any of the embodiments described above, C1-20alkyl is C1-14alkyl. In some embodiments of any of the embodiments described above, C1-20alkyl is C1-125 alkyl. In some embodiments of any of the embodiments described above, C1-20alkyl is C1-10alkyl. In some embodiments of any of the embodiments described above, C1-20alkyl is C1-8alkyl. In some embodiments of any of the embodiments described above, C1-20alkyl is C1-6alkyl. In some embodiments of any of the embodiments described above, C1-20alkyl is C1-4alkyl. In some embodiments of any of the embodiments described above, C1-20alkyl is C1-310 alkyl. In some embodiments of any of the embodiments described above, C2-20alkenyl is C2-18alkenyl. In some embodiments of any of the embodiments described above, C2-20alkenyl is C2-16alkenyl. In some embodiments of any of the embodiments described above, C2-20alkenyl is C2-14alkenyl. In some embodiments of any of the embodiments described above, C2-20alkenyl is C2-1215 alkenyl. In some embodiments of any of the embodiments described above, C2-20alkenyl is C2-10alkenyl. In some embodiments of any of the embodiments described above, C2-20alkenyl is C2-8alkenyl. In some embodiments of any of the embodiments described above, C2-20alkenyl is C2-6alkenyl. In some embodiments of any of the embodiments described above, C2-20 alkenyl is C2-4 alkenyl. In some embodiments of any of the embodiments described above, C2-20alkenyl is C2-320 alkenyl. In some embodiments of any of the embodiments described above, C2-20alkynyl is C2-18alkynyl. In some embodiments of any of the embodiments described above, C2-20alkynyl is C2-16alkynyl. In some embodiments of any of the embodiments described above, C2-20alkynyl is C2-14alkynyl. In some embodiments of any of the embodiments described above, C2-20alkynyl is C2-1225 alkynyl. In some embodiments of any of the embodiments described above, C2-20alkynyl is C2-10alkynyl. In some embodiments of any of the embodiments described above, C2-20alkynyl is C2-8alkynyl. In some embodiments of any of the embodiments described above, C2-20alkynyl is C2-6alkynyl. In some embodiments of any of the embodiments described above, C2-20 alkynyl is C2-4 alkynyl. In some embodiments of any of the embodiments described above, C2-20alkynyl is C2-330 alkynyl. In some embodiments, the compound is a compound of Formula A-I, A-II, A-III, A-IV, or A-V: In some embodiments, the compound is a compound of Formula A-Vaa: or a pharmaceutically acceptable salt thereof, wherein each variable is as defined herein. In some embodiments, the compound is a compound of Formula A-IVa-1, A-IVa-2, A-IVa-3, A-IVb-1, A-IVb-2, A-IVb-3, A-IVb-4, A-IVb-5, A-IVc-1, A-IVc-2, A-IVc-3, A-IVc-4,5 A-IVc-5, A-IVc-6, A-IVc-7, A-IVc-8, A-IVc-9, A-IVc-10, A-IVd-1, A-IVd-2, A-IVd-3, A-IVd- 4, A-IVd-5, A-IVd-6, A-IVd-7, A-IVd-8, A-IVd-9, A-IVd-10, A-IVd-11, A-IVd-12, A-IVd-13, A-IVd-14, A-IVd-15, A-IVd-16, A-IVd-17, A-IVd-18, A-IVd-19, or A-IVd-20:

[0003] Formula A-IVd-19 Formula A-IVd-20, or a pharmaceutically acceptable salt thereof, wherein each variable is as defined herein. In some embodiments, the compound is a compound of Formula A-Va-1, A-Va-2, A-Va- 3 A-Vb-1 A-Vb-2 A-Vb-3 A-Vb-4 A-Vb-5 A-Vc-1 A-Vc-2 A-Vc-3 A-Vc-4 A-Vc-5 6, A-Vd-7, A-Vd-8, A-Vd-9, A-Vd-10, A-Vd-11, A-Vd-12, A-Vd-13, A-Vd-14, A-Vd-15, A-Vd-16, A-Vd-17, A-Vd-18, A-Vd-19, or A-Vd-20:

[0004] or a pharmaceutically acceptable salt thereof, wherein each variable is as defined herein. In some embodiments, the compound is a compound of Formula A-Ia-1, A-Ia-2, A-Ia-3, A-Ib-1, A-Ib-2, A-Ib-3, A-Ib-4, A-Ib-5, A-Ic-1, A-Ic-2, A-Ic-3, A-Ic-4, A-Ic-5, A-Ic-6, A-Ic-7, A-Ic-8, A-Ic-9, A-Ic-10, A-Id-1, A-Id-2, A-Id-3, A-Id-4, A-Id-5, A-Id-6, A-Id-7, A-Id-8, A-Id-9, 5 A-Id-10, A-Id-11, A-Id-12, A-Id-13, A-Id-14, A-Id-15, A-Id-16, A-Id-17, A-Id-18, A-Id-19, or A-Id-20: CF

[0005] or a pharmaceutically acceptable salt thereof, wherein each variable is as defined herein. In some embodiments, the compound is a compound of Formula A-IIIa-1, A-IIIa-2, AIIIa3 AIIIb1 AIIIb2 AIIIb3 AIIIb4 AIIIb5 AIIIc1 AIIIc2 AIIIc3 AIIIc4 A-IIId-5, A-IIId-6, A-IIId-7, A-IIId-8, A-IIId-9, A-IIId-10, A-IIId-11, A-IIId-12, A-IIId-13, A-IIId-14, A-IIId-15, A-IIId-16, A-IIId-17, A-IIId-18, A-IIId-19, or A-IIId-20: 3 3

[0006] or a pharmaceutically acceptable salt thereof, wherein each variable is as defined herein. In some embodiments, the compound is a compound of Formula B-I, B-II, B-III, B-IV, or B-V:

[0007] or a pharmaceutically acceptable salt thereof, wherein each variable is as defined herein.

[0008] In some embodiments, the compound is a compound of Formula B-Vaa: or a pharmac eutically acceptable salt thereof, wherein each variable is as defined herein. In some embodiments, the compound is a compound of Formula B-IVB-1, B-IVB-2, 5 B-IVB-3, B-IVb-1, B-IVb-2, B-IVb-3, B-IVb-4, B-IVb-5, B-IVc-1, B-IVc-2, B-IVc-3, B-IVc-4, B-IVc-5, B-IVc-6, B-IVc-7, B-IVc-8, B-IVc-9, B-IVc-10, B-IVd-1, B-IVd-2, B-IVd-3, B-IVd-4, B-IVd-5, B-IVd-6, B-IVd-7, B-IVd-8, B-IVd-9, B-IVd-10, B-IVd-11, B-IVd-12, B-IVd-13, B-IVd-14, B-IVd-15, B-IVd-16, B-IVd-17, B-IVd-18, B-IVd-19, or B-IVd-20:

[0009] or a pharmaceutically acceptable salt thereof, wherein each variable is as defined herein. In some embodiments, the compound is a compound of Formula B-Va, B-Vb, B-Vc, B-Vd or B-Ve:

[0010] or a pharmaceutically acceptable salt thereof, wherein each variable is as defined herein. In some embodiments, the compound is a compound of Formula B-Vaa: or a pharmaceutically acceptable salt thereof, wherein each variable is as defined herein. In some embodiments, the compound is a compound of Formula B-IVa-1, B-IVa-2, B-5 IVa-3, B-IVb-1, B-IVb-2, B-IVb-3, B-IVb-4, B-IVb-5, B-IVc-1, B-IVc-2, B-IVc-3, B-IVc-4, B- IVc-5, B-IVc-6, B-IVc-7, B-IVc-8, B-IVc-9, B-IVc-10, B-IVd-1, B-IVd-2, B-IVd-3, B-IVd-4, B-IVd-5, B-IVd-6, B-IVd-7, B-IVd-8, B-IVd-9, B-IVd-10, B-IVd-11, B-IVd-12, B-IVd-13, B- IVd-14, B-IVd-15, B-IVd-16, B-IVd-17, B-IVd-18, B-IVd-19, or B-IVd-20:

[0011] or a pharmaceutically acceptable salt thereof, wherein each variable is as defined herein. In some embodiments, the compound is a compound of Formula B-Va-1, B-Va-2, B-Va- 3, B-Vb-1, B-Vb-2, B-Vb-3, B-Vb-4, B-Vb-5, B-Vc-1, B-Vc-2, B-Vc-3, B-Vc-4, B-Vc-5, B-Vc- 6, B-Vc-7, B-Vc-8, B-Vc-9, B-Vc-10, B-Vd-1, B-Vd-2, B-Vd-3, B-Vd-4, B-Vd-5, B-Vd-6, B- 5 Vd-7, B-Vd-8, B-Vd-9, B-Vd-10, B-Vd-11, B-Vd-12, B-Vd-13, B-Vd-14, B-Vd-15, B-Vd-16, B-Vd-17, B-Vd-18, B-Vd-19, or B-Vd-20:

[0012] o ua Vd 9 o ua Vd 0, or a pharmaceutically acceptable salt thereof, wherein each variable is as defined herein. In some embodiments, the compound is a compound of Formula B-Ia-1, B-Ia-2, B-Ia-3, B-Ib-1, B-Ib-2, B-Ib-3, B-Ib-4, B-Ib-5, B-Ic-1, B-Ic-2, B-Ic-3, B-Ic-4, B-Ic-5, B-Ic-6, B-Ic-7, B- Id-10, B-Id-11, B-Id-12, B-Id-13, B-Id-14, B-Id-15, B-Id-16, B-Id-17, B-Id-18, B-Id-19, or B-Id- 20:

[0013] , or a pharmaceutically acceptable salt thereof, wherein each variable is as defined herein. In some embodiments, the compound is a compound of Formula B-IIIa-1, B-IIIa-2, B- IIIa-3, B-IIIb-1, B-IIIb-2, B-IIIb-3, B-IIIb-4, B-IIIb-5, B-IIIc-1, B-IIIc-2, B-IIIc-3, B-IIIc-4, B- IIIc-5, B-IIIc-6, B-IIIc-7, B-IIIc-8, B-IIIc-9, B-IIIc-10, B-IIId-1, B-IIId-2, B-IIId-3, B-IIId-4, B-5 IIId-5, B-IIId-6, B-IIId-7, B-IIId-8, B-IIId-9, B-IIId-10, B-IIId-11, B-IIId-12, B-IIId-13, B-IIId- 14, B-IIId-15, B-IIId-16, B-IIId-17, B-IIId-18, B-IIId-19, or B-IIId-20:

[0014] or a pharmaceutically acceptable salt thereof, wherein each variable is as defined herein. In some embodiments, the compound is a compound of Formula C-I, C-II, C-III, C-IV, or C-V:

[0015] , or a pharmaceutically acceptable salt thereof, an atropisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof, wherein each variable is as defined herein. In some embodiments, the compound is a compound of Formula C-IVa-1, C-IVa-2, C- IVa-3, C-IVb-1, C-IVb-2, C-IVb-3, C-IVb-4, C-IVb-5, C-IVc-1, C-IVc-2, C-IVc-3, C-IVc-4, C- 5 IVc-5, C-IVc-6, C-IVc-7, C-IVc-8, C-IVc-9, C-IVc-10, C-IVd-1, C-IVd-2, C-IVd-3, C-IVd-4, C-IVd-5, C-IVd-6, C-IVd-7, C-IVd-8, C-IVd-9, C-IVd-10, C-IVd-11, C-IVd-12, C-IVd-13, C- IVd-14, C-IVd-15, C-IVd-16, C-IVd-17, C-IVd-18, C-IVd-19, or C-IVd-20:

[0016] or a pharmaceutically acceptable salt thereof, an atropisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof, wherein each variable is as defined herein. In some embodiments the compound is a compound of Formula C-Va-1 C-Va-2 C-Va- 6, C-Vc-7, C-Vc-8, C-Vc-9, C-Vc-10, C-Vd-1, C-Vd-2, C-Vd-3, C-Vd-4, C-Vd-5, C-Vd-6, C- Vd-7, C-Vd-8, C-Vd-9, C-Vd-10, C-Vd-11, C-Vd-12, C-Vd-13, C-Vd-14, C-Vd-15, C-Vd-16, C-Vd-17, C-Vd-18, C-Vd-19, or C-Vd-20:

[0017] or a pharmaceutically acceptable salt thereof, an atropisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof, wherein each variable is as defined herein. In some embodiments, the compound is a compound of Formula C-Ia-1, C-Ia-2, C-Ia-3, C-Ib-1, C-Ib-2, C-Ib-3, C-Ib-4, C-Ib-5, C-Ic-1, C-Ic-2, C-Ic-3, C-Ic-4, C-Ic-5, C-Ic-6, C-Ic-7, C- 5 Ic-8, C-Ic-9, C-Ic-10, C-Id-1, C-Id-2, C-Id-3, C-Id-4, C-Id-5, C-Id-6, C-Id-7, C-Id-8, C-Id-9, C- Id-10, C-Id-11, C-Id-12, C-Id-13, C-Id-14, C-Id-15, C-Id-16, C-Id-17, C-Id-18, C-Id-19, or C-Id- 20:

[0018] , or a pharmaceutically acceptable salt thereof, an atropisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof, wherein each variable is as defined herein. In some embodiments, the compound is a compound of Formula C-IIIa-1, C-IIIa-2, C- IIIc-5, C-IIIc-6, C-IIIc-7, C-IIIc-8, C-IIIc-9, C-IIIc-10, C-IIId-1, C-IIId-2, C-IIId-3, C-IIId-4, C- IIId-5, C-IIId-6, C-IIId-7, C-IIId-8, C-IIId-9, C-IIId-10, C-IIId-11, C-IIId-12, C-IIId-13, C-IIId- 14, C-IIId-15, C-IIId-16, C-IIId-17, C-IIId-18, C-IIId-19, or C-IIId-20:

[0019] or a pharmaceutically acceptable salt thereof, an atropisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof, wherein each variable is as defined herein. In some embodiments, the compound is a compound shown in Table 1, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is a compound 5 shown in Table 2, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is a compound shown in Table 2, or a pharmaceutically acceptable salt thereof, an atropisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof. As used herein, the abbreviation “CMPD” or “cmpd” refers to “compound.”

[0020] The compounds in Table 1 or Table 2 were made in accordance with synthetic procedures described in the Examples section, or similar procedures that would be readily understood by a 5 person of skill in the art on the basis of the instant disclosure and knowledge present in the art. The compounds marked with (*) in Table 1 or Table 2 are prophetic examples and can be made or isolated by methods similar to those included in the Examples section. In some embodiments, the compound is compound 101-A. In some embodiments, the compound is compound 101-B. 5 In some embodiments, the compound is compound 201. In some embodiments, the compound is compound 201-A. In some embodiments, the compound is compound 201-B. In some embodiments, the compound is a mixture of compound 201-A and 201-B. In some embodiments, the compound is compound 202. In some embodiments, the compound is compound 202-A. In some embodiments, the compound is compound 202-B. In some 10 embodiments, the compound is a mixture of compound 202-A and 202-B. In some embodiments, the compound is compound 203. In some embodiments, the compound is compound 203-A. In some embodiments, the compound is compound 203-B. In some embodiments, the compound is a mixture of compound 203-A and 203-B. In some embodiments, the compound is compound 204. In some embodiments, the compound is 15 compound 204-A. In some embodiments, the compound is compound 204-B. In some embodiments, the compound is a mixture of compound 204-A and 204-B. In some embodiments, the compound is compound 205. In some embodiments, the compound is compound 205-A. In some embodiments, the compound is compound 205-B. In some embodiments, the compound is a mixture of compound 205-A and 205-B. In some 20 embodiments, the compound is compound 206. In some embodiments, the compound is compound 206-A. In some embodiments, the compound is compound 206-B. In some embodiments, the compound is a mixture of compound 206-A and 206-B. In some embodiments, the compound is compound 207. In some embodiments, the compound is compound 207-A. In some embodiments, the compound is compound 207-B. In some 25 embodiments, the compound is a mixture of compound 207-A and 207-B. In some embodiments, the compound is compound 208. In some embodiments, the compound is compound 208-A. In some embodiments, the compound is compound 208-B. In some embodiments, the compound is a mixture of compound 208-A and 208-B. In some embodiments, the compound is compound 209. In some embodiments, the compound is 30 compound 209-A. In some embodiments, the compound is compound 209-B. In some embodiments, the compound is a mixture of compound 209-A and 209-B. In some embodiments, the compound is compound 210. In some embodiments, the compound is compound 210-A. In some embodiments, the compound is compound 210-B. In some embodiments, the compound is compound 211. In some embodiments, the compound is compound 211-A. In some embodiments, the compound is compound 211-B. In some embodiments, the compound is a mixture of compound 211-A and 211-B. In some embodiments, the compound is compound 212. In some embodiments, the compound is 5 compound 212-A. In some embodiments, the compound is compound 212-B. In some embodiments, the compound is a mixture of compound 212-A and 212-B. In some embodiments, the compound is compound 213. In some embodiments, the compound is compound 213-A. In some embodiments, the compound is compound 213-B. In some embodiments, the compound is a mixture of compound 213-A and 213-B. In some 10 embodiments, the compound is compound 214. In some embodiments, the compound is compound 214-A. In some embodiments, the compound is compound 214-B. In some embodiments, the compound is a mixture of compound 214-A and 214-B. In some embodiments, the compound is compound 215. In some embodiments, the compound is compound 215-A. In some embodiments, the compound is compound 215-B. In some 15 embodiments, the compound is a mixture of compound 215-A and 215-B. In some embodiments, the compound is compound 216. In some embodiments, the compound is compound 216-A. In some embodiments, the compound is compound 216-B. In some embodiments, the compound is a mixture of compound 216-A and 216-B. In some embodiments, the compound is compound 217. In some embodiments, the compound is 20 compound 217-A. In some embodiments, the compound is compound 217-B. In some embodiments, the compound is a mixture of compound 217-A and 217-B. In some embodiments, the compound is compound 218. In some embodiments, the compound is compound 218-A. In some embodiments, the compound is compound 218-B. In some embodiments, the compound is a mixture of compound 218-A and 218-B. In some 25 embodiments, the compound is compound 219. In some embodiments, the compound is compound 219-A. In some embodiments, the compound is compound 219-B. In some embodiments, the compound is a mixture of compound 219-A and 219-B. In some embodiments, the compound is compound 220. In some embodiments, the compound is compound 220-A. In some embodiments, the compound is compound 220-B. In some 30 embodiments, the compound is a mixture of compound 220-A and 220-B. In some embodiments, the compound is compound 221. In some embodiments, the compound is compound 221-A. In some embodiments, the compound is compound 221-B. In some embodiments, the compound is a mixture of compound 221-A and 221-B. In some embodiments, the compound is compound 222. In some embodiments, the compound is compound 222-A. In some embodiments, the compound is compound 222-B. In some embodiments, the compound is a mixture of compound 222-A and 222-B. In some embodiments, the compound is compound 223. In some embodiments, the compound is compound 223-A. In some embodiments, the compound is compound 223-B. In some 5 embodiments, the compound is a mixture of compound 223-A and compound 223-B. In some embodiments, the compound is compound 224. In some embodiments, the compound is compound 224-A. In some embodiments, the compound is compound 224-B. In some embodiments, the compound is a mixture of compound 224-A and compound 224-B. In some embodiments, the compound is compound 225. In some embodiments, the compound is 10 compound 225-A. In some embodiments, the compound is compound 225-B. In some embodiments, the compound is a mixture of compound 225-A and compound 225-B. In some embodiments, the compound is compound 226. In some embodiments, the compound is compound 226-A. In some embodiments, the compound is compound 226-B. In some embodiments, the compound is a mixture of compound 226-A and compound 226-B. In some 15 embodiments, the compound is compound 227. In some embodiments, the compound is compound 227-A. In some embodiments, the compound is compound 227-B. In some embodiments, the compound is a mixture of compound 227-A and compound 227-B. In some embodiments, the compound is compound 228. In some embodiments, the compound is compound 228-A. In some embodiments, the compound is compound 228-B. In some 20 embodiments, the compound is a mixture of compound 228-A and compound 228-B. In some embodiments, the compound is compound 229. In some embodiments, the compound is compound 229-A. In some embodiments, the compound is compound 229-B. In some embodiments, the compound is a mixture of compound 229-A and compound 229-B. In some embodiments, the compound is compound 230. In some embodiments, the compound is 25 compound 230-A. In some embodiments, the compound is compound 230-B. In some embodiments, the compound is a mixture of compound 230-A and compound 230-B. In some embodiments, the compound is compound 231. In some embodiments, the compound is compound 231-A. In some embodiments, the compound is compound 231-B. In some embodiments, the compound is a mixture of compound 231-A and compound 231-B. In some 30 embodiments, the compound is compound 232. In some embodiments, the compound is compound 232-A. In some embodiments, the compound is compound 232-B. In some embodiments, the compound is a mixture of compound 232-A and compound 232-B. In some embodiments, the compound is compound 233. In some embodiments, the compound is compound 233-A. In some embodiments, the compound is compound 233-B. In some embodiments, the compound is a mixture of compound 233-A and compound 233-B. In some embodiments, the compound is compound 234. In some embodiments, the compound is compound 234-A. In some embodiments, the compound is compound 234-B. In some embodiments, the compound is a mixture of compound 234-A and compound 234-B. In some 5 embodiments, the compound is compound 235. In some embodiments, the compound is compound 235-A. In some embodiments, the compound is compound 235-B. In some embodiments, the compound is a mixture of compound 235-A and compound 235-B. In some embodiments, the compound is compound 236. In some embodiments, the compound is compound 236-A. In some embodiments, the compound is compound 236-B. In some 10 embodiments, the compound is a mixture of compound 236-A and compound 236-B. In some embodiments, the compound is compound 237. In some embodiments, the compound is compound 237-A. In some embodiments, the compound is compound 237-B. In some embodiments, the compound is a mixture of compound 237-A and compound 237-B. In some embodiments, the compound is compound 238. In some embodiments, the compound is 15 compound 238-A. In some embodiments, the compound is compound 238-B. In some embodiments, the compound is a mixture of compound 238-A and compound 238-B. In some embodiments, the compound is compound 239. In some embodiments, the compound is compound 239-A. In some embodiments, the compound is compound 239-B. In some embodiments, the compound is a mixture of compound 239-A and compound 239-B. In some 20 embodiments, the compound is compound 240. In some embodiments, the compound is compound 240-A. In some embodiments, the compound is compound 240-B. In some embodiments, the compound is a mixture of compound 240-A and compound 240-B. In some embodiments, the compound is compound 241. In some embodiments, the compound is compound 241-A. In some embodiments, the compound is compound 241-B. In some 25 embodiments, the compound is a mixture of compound 241-A and compound 241-B. In some embodiments, the compound is compound 242. In some embodiments, the compound is compound 242-A. In some embodiments, the compound is compound 242-B. In some embodiments, the compound is a mixture of compound 242-A and compound 242-B. In some embodiments, the compound is compound 243. In some embodiments, the compound is 30 compound 243-A. In some embodiments, the compound is compound 243-B. In some embodiments, the compound is a mixture of compound 243-A and compound 243-B. In some embodiments, the compound is compound 244. In some embodiments, the compound is compound 244-A. In some embodiments, the compound is compound 244-B. In some embodiments, the compound is a mixture of compound 244-A and compound 244-B. In some embodiments, the compound is compound 245. In some embodiments, the compound is compound 245-A. In some embodiments, the compound is compound 245-B. In some embodiments, the compound is a mixture of compound 245-A and compound 245-B. In some embodiments, the compound is compound 246. In some embodiments, the compound is 5 compound 246-A. In some embodiments, the compound is compound 246-B. In some embodiments, the compound is a mixture of compound 246-A and compound 246-B. In some embodiments, the compound is compound 247. In some embodiments, the compound is compound 247-A. In some embodiments, the compound is compound 247-B. In some embodiments, the compound is a mixture of compound 247-A and compound 247-B. In some 10 embodiments, the compound is compound 248. In some embodiments, the compound is compound 248-A. In some embodiments, the compound is compound 248-B. In some embodiments, the compound is a mixture of compound 248-A and compound 248-B. In some embodiments, the compound is compound 249. In some embodiments, the compound is compound 249-A. In some embodiments, the compound is compound 249-B. In some 15 embodiments, the compound is a mixture of compound 249-A and compound 249-B. In some embodiments, the compound is compound 250. In some embodiments, the compound is compound 250-A. In some embodiments, the compound is compound 250-B. In some embodiments, the compound is a mixture of compound 250-A and compound 250-B. In some embodiments, the compound is compound 251. In some embodiments, the compound is 20 compound 251-A. In some embodiments, the compound is compound 251-B. In some embodiments, the compound is a mixture of compound 251-A and compound 251-B. In some embodiments, the compound is compound 252. In some embodiments, the compound is compound 252-A. In some embodiments, the compound is compound 252-B. In some embodiments, the compound is a mixture of compound 252-A and compound 252-B. In some 25 embodiments, the compound is compound 253. In some embodiments, the compound is compound 253-A. In some embodiments, the compound is compound 253-B. In some embodiments, the compound is a mixture of compound 253-A and compound 253-B. In some embodiments, the compound is compound 254. In some embodiments, the compound is compound 254-A. In some embodiments, the compound is compound 254-B. In some 30 embodiments, the compound is a mixture of compound 254-A and compound 254-B. In some embodiments, the compound is compound 255. In some embodiments, the compound is compound 255-A. In some embodiments, the compound is compound 255-B. In some embodiments, the compound is a mixture of compound 255-A and compound 255-B. In some embodiments, the compound is compound 256. In some embodiments, the compound is compound 256-A. In some embodiments, the compound is compound 256-B. In some embodiments, the compound is a mixture of compound 256-A and compound 256-B. In some embodiments, the compound is compound 257. In some embodiments, the compound is compound 257-A. In some embodiments, the compound is compound 257-B. In some 5 embodiments, the compound is a mixture of compound 257-A and compound 257-B. In some embodiments, the compound is compound 258. In some embodiments, the compound is compound 258-A. In some embodiments, the compound is compound 258-B. In some embodiments, the compound is a mixture of compound 258-A and compound 258-B. In some embodiments, the compound is compound 259. In some embodiments, the compound is 10 compound 259-A. In some embodiments, the compound is compound 259-B. In some embodiments, the compound is a mixture of compound 259-A and compound 259-B. In some embodiments, the compound is compound 260. In some embodiments, the compound is compound 260-A. In some embodiments, the compound is compound 260-B. In some embodiments, the compound is a mixture of compound 260-A and compound 260-B. In some 15 embodiments, the compound is compound 261. In some embodiments, the compound is compound 261-A. In some embodiments, the compound is compound 261-B. In some embodiments, the compound is a mixture of compound 261-A and compound 261-B. In some embodiments, the compound is compound 262. In some embodiments, the compound is compound 262-A. In some embodiments, the compound is compound 262-B. In some 20 embodiments, the compound is a mixture of compound 262-A and compound 262-B. In some embodiments, the compound is compound 263. In some embodiments, the compound is compound 263-A. In some embodiments, the compound is compound 263-B. In some embodiments, the compound is a mixture of compound 263-A and compound 263-B. In some embodiments, the compound is compound 264. In some embodiments, the compound is 25 compound 264-A. In some embodiments, the compound is compound 264-B. In some embodiments, the compound is a mixture of compound 264-A and compound 264-B. In some embodiments, the compound is compound 265. In some embodiments, the compound is compound 265-A. In some embodiments, the compound is compound 265-B. In some embodiments, the compound is a mixture of compound 265-A and compound 265-B. In some 30 embodiments, the compound is compound 266. In some embodiments, the compound is compound 266-A. In some embodiments, the compound is compound 266-B. In some embodiments, the compound is a mixture of compound 266-A and compound 266-B. In some embodiments, the compound is compound 267. In some embodiments, the compound is compound 267-A. In some embodiments, the compound is compound 267-B. In some embodiments, the compound is a mixture of compound 267-A and compound 267-B. In some embodiments, the compound is compound 268. In some embodiments, the compound is compound 268-A. In some embodiments, the compound is compound 268-B. In some embodiments, the compound is a mixture of compound 268-A and compound 268-B. In some 5 embodiments, the compound is compound 269. In some embodiments, the compound is compound 269-A. In some embodiments, the compound is compound 269-B. In some embodiments, the compound is a mixture of compound 269-A and compound 269-B. In some embodiments, the compound is compound 270. In some embodiments, the compound is compound 270-A. In some embodiments, the compound is compound 270-B. In some 10 embodiments, the compound is a mixture of compound 270-A and compound 270-B. In some embodiments, the compound is compound 271. In some embodiments, the compound is compound 271-A1. In some embodiments, the compound is compound 271-A2. In some embodiments, the compound is compound 271-B1. In some embodiments, the compound is compound 271-B2. In some embodiments, the compound is a mixture of compound 271-A1 and 15 compound 271-B2. In some embodiments, the compound is a mixture of compound 271-A2 and compound 271-B1. In some embodiments, the compound is a mixture of compound 271-A1, compound 271-A2, compound 271-B1, and compound 271-B2. In some embodiments, the compound is compound 272. In some embodiments, the compound is compound 272-A. In some embodiments, the compound is compound 272-B. In some embodiments, the compound is a 20 mixture of compound 272-A and compound 272-B. In some embodiments, the compound is compound 273. In some embodiments, the compound is compound 273-A. In some embodiments, the compound is compound 273-B. In some embodiments, the compound is a mixture of compound 273-A and compound 273-B. In some embodiments, the compound is compound 274. In some embodiments, the compound is compound 274-A. In some 25 embodiments, the compound is compound 274-B. In some embodiments, the compound is a mixture of compound 274-A and compound 274-B. In some embodiments, the compound is compound 275. In some embodiments, the compound is compound 275-A. In some embodiments, the compound is compound 275-B. In some embodiments, the compound is a mixture of compound 275-A and compound 275-B. In some embodiments, the compound is 30 compound 276. In some embodiments, the compound is compound 276-A. In some embodiments, the compound is compound 276-B. In some embodiments, the compound is a mixture of compound 276-A and compound 276-B. In some embodiments, the compound is compound 277. In some embodiments, the compound is compound 277-A1. In some embodiments, the compound is compound 277-A2. In some embodiments, the compound is compound 277-B1. In some embodiments, the compound is compound 277-B2. In some embodiments, the compound is a mixture of compound 277-A1 and compound 277-B2. In some embodiments, the compound is a mixture of compound 277-A2 and compound 277-B1. In some embodiments, the compound is a mixture of compound 277-A1, compound 277-A2, compound 5 277-B1, and compound 277-B2. In some embodiments, the compound is compound 278. In some embodiments, the compound is compound 278-A1. In some embodiments, the compound is compound 278-A2. In some embodiments, the compound is compound 278-B1. In some embodiments, the compound is compound 278-B2. In some embodiments, the compound is a mixture of compound 278-A1 and compound 278-B2. In some embodiments, the compound is a 10 mixture of compound 278-A2 and compound 278-B1. In some embodiments, the compound is a mixture of compound 278-A1, compound 278-A2, compound 278-B1, and compound 278-B2. In some embodiments, the compound is compound 279. In some embodiments, the compound is compound 279-A. In some embodiments, the compound is compound 279-B. In some embodiments, the compound is a mixture of compound 279-A and compound 279-B. In some 15 embodiments, the compound is compound 280. In some embodiments, the compound is compound 280-A. In some embodiments, the compound is compound 280-B. In some embodiments, the compound is a mixture of compound 280-A and compound 280-B. In some embodiments, the compound is compound 281. In some embodiments, the compound is compound 281-A. In some embodiments, the compound is compound 281-B. In some 20 embodiments, the compound is a mixture of compound 281-A and compound 281-B. In some embodiments, the compound is compound 282. In some embodiments, the compound is compound 282-A. In some embodiments, the compound is compound 282-B. In some embodiments, the compound is a mixture of compound 282-A and compound 282-B. In some embodiments, a composition comprises compound 101-A. In some 25 embodiments, a composition comprises compound 101-B. In some embodiments, a composition comprises compound 201. In some embodiments, a composition comprises compound 201-A. In some embodiments, a composition comprises compound 201-B. In some embodiments, a composition comprises a mixture of compound 201- A and 201-B. In some embodiments, a composition comprises compound 202. In some 30 embodiments, a composition comprises compound 202-A. In some embodiments, a composition comprises compound 202-B. In some embodiments, a composition comprises a mixture of compound 202-A and 202-B. In some embodiments, a composition comprises compound 203. In some embodiments, a composition comprises compound 203-A. In some embodiments, a composition comprises compound 203-B. In some embodiments, a composition comprises a mixture of compound 203-A and 203-B. In some embodiments, a composition comprises compound 204. In some embodiments, a composition comprises compound 204-A. In some embodiments, a composition comprises compound 204-B. In some embodiments, a composition comprises a mixture of compound 204-A and 204-B. In some embodiments, a composition 5 comprises compound 205. In some embodiments, a composition comprises compound 205-A. In some embodiments, a composition comprises compound 205-B. In some embodiments, a composition comprises a mixture of compound 205-A and 205-B. In some embodiments, a composition comprises compound 206. In some embodiments, a composition comprises compound 206-A. In some embodiments, a composition comprises compound 206-B. In some 10 embodiments, a composition comprises a mixture of compound 206-A and 206-B. In some embodiments, a composition comprises compound 207. In some embodiments, a composition comprises compound 207-A. In some embodiments, a composition comprises compound 207-B. In some embodiments, a composition comprises a mixture of compound 207-A and 207-B. In some embodiments, a composition comprises compound 208. In some embodiments, a 15 composition comprises compound 208-A. In some embodiments, a composition comprises compound 208-B. In some embodiments, a composition comprises a mixture of compound 208- A and 208-B. In some embodiments, a composition comprises compound 209. In some embodiments, a composition comprises compound 209-A. In some embodiments, a composition comprises compound 209-B. In some embodiments, a composition comprises a mixture of 20 compound 209-A and 209-B. In some embodiments, a composition comprises compound 210. In some embodiments, a composition comprises compound 210-A. In some embodiments, a composition comprises compound 210-B. In some embodiments, a composition comprises a mixture of compound 210-A and 210-B. In some embodiments, a composition comprises compound 211. In some embodiments, a composition comprises compound 211-A. In some 25 embodiments, a composition comprises compound 211-B. In some embodiments, a composition comprises a mixture of compound 211-A and 211-B. In some embodiments, a composition comprises compound 212. In some embodiments, a composition comprises compound 212-A. In some embodiments, a composition comprises compound 212-B. In some embodiments, a composition comprises a mixture of compound 212-A and 212-B. In some embodiments, a 30 composition comprises compound 213. In some embodiments, a composition comprises compound 213-A. In some embodiments, a composition comprises compound 213-B. In some embodiments, a composition comprises a mixture of compound 213-A and 213-B. In some embodiments, a composition comprises compound 214. In some embodiments, a composition comprises compound 214-A. In some embodiments, a composition comprises compound 214-B. In some embodiments, a composition comprises a mixture of compound 214-A and 214-B. In some embodiments, a composition comprises compound 215. In some embodiments, a composition comprises compound 215-A. In some embodiments, a composition comprises compound 215-B. In some embodiments, a composition comprises a mixture of compound 215- 5 A and 215-B. In some embodiments, a composition comprises compound 216. In some embodiments, a composition comprises compound 216-A. In some embodiments, a composition comprises compound 216-B. In some embodiments, a composition comprises a mixture of compound 216-A and 216-B. In some embodiments, a composition comprises compound 217. In some embodiments, a composition comprises compound 217-A. In some embodiments, a 10 composition comprises compound 217-B. In some embodiments, a composition comprises a mixture of compound 217-A and 217-B. In some embodiments, a composition comprises compound 218. In some embodiments, a composition comprises compound 218-A. In some embodiments, a composition comprises compound 218-B. In some embodiments, a composition comprises a mixture of compound 218-A and 218-B. In some embodiments, a composition 15 comprises compound 219. In some embodiments, a composition comprises compound 219-A. In some embodiments, a composition comprises compound 219-B. In some embodiments, a composition comprises a mixture of compound 219-A and 219-B. In some embodiments, a composition comprises compound 220. In some embodiments, a composition comprises compound 220-A. In some embodiments, a composition comprises compound 220-B. In some 20 embodiments, a composition comprises a mixture of compound 220-A and 220-B. In some embodiments, a composition comprises compound 221. In some embodiments, a composition comprises compound 221-A. In some embodiments, a composition comprises compound 221-B. In some embodiments, a composition comprises a mixture of compound 221-A and 221-B. In some embodiments, a composition comprises compound 222. In some embodiments, a 25 composition comprises compound 222-A. In some embodiments, a composition comprises compound 222-B. In some embodiments, a composition comprises a mixture of compound 222- A and 222-B. In some embodiments, a composition comprises compound 223. In some embodiments, a composition comprises compound 223-A. In some embodiments, a composition comprises compound 223-B. In some embodiments, a composition comprises a mixture of 30 compound 223-A and compound 223-B. In some embodiments, a composition comprises compound 224. In some embodiments, a composition comprises compound 224-A. In some embodiments, a composition comprises compound 224-B. In some embodiments, a composition comprises a mixture of compound 224-A and compound 224-B. In some embodiments, a composition comprises compound 225. In some embodiments, a composition comprises compound 225-A. In some embodiments, a composition comprises compound 225-B. In some embodiments, a composition comprises a mixture of compound 225-A and compound 225-B. In some embodiments, a composition comprises compound 226. In some embodiments, a composition comprises compound 226-A. In some embodiments, a composition comprises 5 compound 226-B. In some embodiments, a composition comprises a mixture of compound 226- A and compound 226-B. In some embodiments, a composition comprises compound 227. In some embodiments, a composition comprises compound 227-A. In some embodiments, a composition comprises compound 227-B. In some embodiments, a composition comprises a mixture of compound 227-A and compound 227-B. In some embodiments, a composition 10 comprises compound 228. In some embodiments, a composition comprises compound 228-A. In some embodiments, a composition comprises compound 228-B. In some embodiments, a composition comprises a mixture of compound 228-A and compound 228-B. In some embodiments, a composition comprises compound 229. In some embodiments, a composition comprises compound 229-A. In some embodiments, a composition comprises compound 229-B. 15 In some embodiments, a composition comprises a mixture of compound 229-A and compound 229-B. In some embodiments, a composition comprises compound 230. In some embodiments, a composition comprises compound 230-A. In some embodiments, a composition comprises compound 230-B. In some embodiments, a composition comprises a mixture of compound 230- A and compound 230-B. In some embodiments, a composition comprises compound 231. In 20 some embodiments, a composition comprises compound 231-A. In some embodiments, a composition comprises compound 231-B. In some embodiments, a composition comprises a mixture of compound 231-A and compound 231-B. In some embodiments, a composition comprises compound 232. In some embodiments, a composition comprises compound 232-A. In some embodiments, a composition comprises compound 232-B. In some embodiments, a 25 composition comprises a mixture of compound 232-A and compound 232-B. In some embodiments, a composition comprises compound 233. In some embodiments, a composition comprises compound 233-A. In some embodiments, a composition comprises compound 233-B. In some embodiments, a composition comprises a mixture of compound 233-A and compound 233-B. In some embodiments, a composition comprises compound 234. In some embodiments, a 30 composition comprises compound 234-A. In some embodiments, a composition comprises compound 234-B. In some embodiments, a composition comprises a mixture of compound 234- A and compound 234-B. In some embodiments, a composition comprises compound 235. In some embodiments, a composition comprises compound 235-A. In some embodiments, a composition comprises compound 235-B. In some embodiments, a composition comprises a mixture of compound 235-A and compound 235-B. In some embodiments, a composition comprises compound 236. In some embodiments, a composition comprises compound 236-A. In some embodiments, a composition comprises compound 236-B. In some embodiments, a composition comprises a mixture of compound 236-A and compound 236-B. In some 5 embodiments, a composition comprises compound 237. In some embodiments, a composition comprises compound 237-A. In some embodiments, a composition comprises compound 237-B. In some embodiments, a composition comprises a mixture of compound 237-A and compound 237-B. In some embodiments, a composition comprises compound 238. In some embodiments, a composition comprises compound 238-A. In some embodiments, a composition comprises10 compound 238-B. In some embodiments, a composition comprises a mixture of compound 238- A and compound 238-B. In some embodiments, a composition comprises compound 239. In some embodiments, a composition comprises compound 239-A. In some embodiments, a composition comprises compound 239-B. In some embodiments, a composition comprises a mixture of compound 239-A and compound 239-B. In some embodiments, a composition 15 comprises compound 240. In some embodiments, a composition comprises compound 240-A. In some embodiments, a composition comprises compound 240-B. In some embodiments, a composition comprises a mixture of compound 240-A and compound 240-B. In some embodiments, a composition comprises compound 241. In some embodiments, a composition comprises compound 241-A. In some embodiments, a composition comprises compound 241-B. 20 In some embodiments, a composition comprises a mixture of compound 241-A and compound 241-B. In some embodiments, a composition comprises compound 242. In some embodiments, a composition comprises compound 242-A. In some embodiments, a composition comprises compound 242-B. In some embodiments, a composition comprises a mixture of compound 242- A and compound 242-B. In some embodiments, a composition comprises compound 243. In 25 some embodiments, a composition comprises compound 243-A. In some embodiments, a composition comprises compound 243-B. In some embodiments, a composition comprises a mixture of compound 243-A and compound 243-B. In some embodiments, a composition comprises compound 244. In some embodiments, a composition comprises compound 244-A. In some embodiments, a composition comprises compound 244-B. In some embodiments, a 30 composition comprises a mixture of compound 244-A and compound 244-B. In some embodiments, a composition comprises compound 245. In some embodiments, a composition comprises compound 245-A. In some embodiments, a composition comprises compound 245-B. In some embodiments, a composition comprises a mixture of compound 245-A and compound 245-B. In some embodiments, a composition comprises compound 246. In some embodiments, a composition comprises compound 246-A. In some embodiments, a composition comprises compound 246-B. In some embodiments, a composition comprises a mixture of compound 246- A and compound 246-B. In some embodiments, a composition comprises compound 247. In some embodiments, a composition comprises compound 247-A. In some embodiments, a 5 composition comprises compound 247-B. In some embodiments, a composition comprises a mixture of compound 247-A and compound 247-B. In some embodiments, a composition comprises compound 248. In some embodiments, a composition comprises compound 248-A. In some embodiments, a composition comprises compound 248-B. In some embodiments, a composition comprises a mixture of compound 248-A and compound 248-B. In some 10 embodiments, a composition comprises compound 249. In some embodiments, a composition comprises compound 249-A. In some embodiments, a composition comprises compound 249-B. In some embodiments, a composition comprises a mixture of compound 249-A and compound 249-B. In some embodiments, a composition comprises compound 250. In some embodiments, a composition comprises compound 250-A. In some embodiments, a composition comprises15 compound 250-B. In some embodiments, a composition comprises a mixture of compound 250- A and compound 250-B. In some embodiments, a composition comprises compound 251. In some embodiments, a composition comprises compound 251-A. In some embodiments, a composition comprises compound 251-B. In some embodiments, a composition comprises a mixture of compound 251-A and compound 251-B. In some embodiments, a composition 20 comprises compound 252. In some embodiments, a composition comprises compound 252-A. In some embodiments, a composition comprises compound 252-B. In some embodiments, a composition comprises a mixture of compound 252-A and compound 252-B. In some embodiments, a composition comprises compound 253. In some embodiments, a composition comprises compound 253-A. In some embodiments, a composition comprises compound 253-B. 25 In some embodiments, a composition comprises a mixture of compound 253-A and compound 253-B. In some embodiments, a composition comprises compound 254. In some embodiments, a composition comprises compound 254-A. In some embodiments, a composition comprises compound 254-B. In some embodiments, a composition comprises a mixture of compound 254- A and compound 254-B. In some embodiments, a composition comprises compound 255. In 30 some embodiments, a composition comprises compound 255-A. In some embodiments, a composition comprises compound 255-B. In some embodiments, a composition comprises a mixture of compound 255-A and compound 255-B. In some embodiments, a composition comprises compound 256. In some embodiments, a composition comprises compound 256-A. In some embodiments, a composition comprises compound 256-B. In some embodiments, a composition comprises a mixture of compound 256-A and compound 256-B. In some embodiments, a composition comprises compound 257. In some embodiments, a composition comprises compound 257-A. In some embodiments, a composition comprises compound 257-B. In some embodiments, a composition comprises a mixture of compound 257-A and compound 5 257-B. In some embodiments, a composition comprises compound 258. In some embodiments, a composition comprises compound 258-A. In some embodiments, a composition comprises compound 258-B. In some embodiments, a composition comprises a mixture of compound 258- A and compound 258-B. In some embodiments, a composition comprises compound 259. In some embodiments, a composition comprises compound 259-A. In some embodiments, a 10 composition comprises compound 259-B. In some embodiments, a composition comprises a mixture of compound 259-A and compound 259-B. In some embodiments, a composition comprises compound 260. In some embodiments, a composition comprises compound 260-A. In some embodiments, a composition comprises compound 260-B. In some embodiments, a composition comprises a mixture of compound 260-A and compound 260-B. In some 15 embodiments, a composition comprises compound 261. In some embodiments, a composition comprises compound 261-A. In some embodiments, a composition comprises compound 261-B. In some embodiments, a composition comprises a mixture of compound 261-A and compound 261-B. In some embodiments, a composition comprises compound 262. In some embodiments, a composition comprises compound 262-A. In some embodiments, a composition comprises20 compound 262-B. In some embodiments, a composition comprises a mixture of compound 262- A and compound 262-B. In some embodiments, a composition comprises compound 263. In some embodiments, a composition comprises compound 263-A. In some embodiments, a composition comprises compound 263-B. In some embodiments, a composition comprises a mixture of compound 263-A and compound 263-B. In some embodiments, a composition 25 comprises compound 264. In some embodiments, a composition comprises compound 264-A. In some embodiments, a composition comprises compound 264-B. In some embodiments, a composition comprises a mixture of compound 264-A and compound 264-B. In some embodiments, a composition comprises compound 265. In some embodiments, a composition comprises compound 265-A. In some embodiments, a composition comprises compound 265-B. 30 In some embodiments, a composition comprises a mixture of compound 265-A and compound 265-B. In some embodiments, a composition comprises compound 266. In some embodiments, a composition comprises compound 266-A. In some embodiments, a composition comprises compound 266-B. In some embodiments, a composition comprises a mixture of compound 266- A and compound 266-B. In some embodiments, a composition comprises compound 267. In some embodiments, a composition comprises compound 267-A. In some embodiments, a composition comprises compound 267-B. In some embodiments, a composition comprises a mixture of compound 267-A and compound 267-B. In some embodiments, a composition comprises compound 268. In some embodiments, a composition comprises compound 268-A. In 5 some embodiments, a composition comprises compound 268-B. In some embodiments, a composition comprises a mixture of compound 268-A and compound 268-B. In some embodiments, a composition comprises compound 269. In some embodiments, a composition comprises compound 269-A. In some embodiments, a composition comprises compound 269-B. In some embodiments, a composition comprises a mixture of compound 269-A and compound 10 269-B. In some embodiments, a composition comprises compound 270. In some embodiments, a composition comprises compound 270-A. In some embodiments, a composition comprises compound 270-B. In some embodiments, a composition comprises a mixture of compound 270- A and compound 270-B. In some embodiments, a composition comprises compound 271. In some embodiments, a composition comprises compound 271-A1. In some embodiments, a 15 composition comprises compound 271-A2. In some embodiments, a composition comprises compound 271-B1. In some embodiments, a composition comprises compound 271-B2. In some embodiments, a composition comprises a mixture of compound 271-A1 and compound 271-B2. In some embodiments, a composition comprises a mixture of compound 271-A2 and compound 271-B1. In some embodiments, a composition comprises a mixture of compound 271-A1, 20 compound 271-A2, compound 271-B1, and compound 271-B2. In some embodiments, a composition comprises compound 272. In some embodiments, a composition comprises compound 272-A. In some embodiments, a composition comprises compound 272-B. In some embodiments, a composition comprises a mixture of compound 272-A and compound 272-B. In some embodiments, a composition comprises compound 273. In some embodiments, a 25 composition comprises compound 273-A. In some embodiments, a composition comprises compound 273-B. In some embodiments, a composition comprises a mixture of compound 273- A and compound 273-B. In some embodiments, a composition comprises compound 274. In some embodiments, a composition comprises compound 274-A. In some embodiments, a composition comprises compound 274-B. In some embodiments, a composition comprises a 30 mixture of compound 274-A and compound 274-B. In some embodiments, a composition comprises compound 275. In some embodiments, a composition comprises compound 275-A. In some embodiments, a composition comprises compound 275-B. In some embodiments, a composition comprises a mixture of compound 275-A and compound 275-B. In some embodiments, a composition comprises compound 276. In some embodiments, a composition comprises compound 276-A. In some embodiments, a composition comprises compound 276-B. In some embodiments, a composition comprises a mixture of compound 276-A and compound 276-B. In some embodiments, a composition comprises compound 277. In some embodiments, a composition comprises compound 277-A1. In some embodiments, a composition comprises 5 compound 277-A2. In some embodiments, a composition comprises compound 277-B1. In some embodiments, a composition comprises compound 277-B2. In some embodiments, a composition comprises a mixture of compound 277-A1 and compound 277-B2. In some embodiments, a composition comprises a mixture of compound 277-A2 and compound 277-B1. In some embodiments, a composition comprises a mixture of compound 277-A1, compound 10 277-A2, compound 277-B1, and compound 277-B2. In some embodiments, a composition comprises compound 278. In some embodiments, a composition comprises compound 278-A1. In some embodiments, a composition comprises compound 278-A2. In some embodiments, a composition comprises compound 278-B1. In some embodiments, a composition comprises compound 278-B2. In some embodiments, a composition comprises a mixture of compound 278- 15 A1 and compound 278-B2. In some embodiments, a composition comprises a mixture of compound 278-A2 and compound 278-B1. In some embodiments, a composition comprises a mixture of compound 278-A1, compound 278-A2, compound 278-B1, and compound 278-B2. In some embodiments, a composition comprises compound 279. In some embodiments, a composition comprises compound 279-A. In some embodiments, a composition comprises20 compound 279-B. In some embodiments, a composition comprises a mixture of compound 279- A and compound 279-B. In some embodiments, a composition comprises compound 280. In some embodiments, a composition comprises compound 280-A. In some embodiments, a composition comprises compound 280-B. In some embodiments, a composition comprises a mixture of compound 280-A and compound 280-B. In some embodiments, a composition 25 comprises compound 281. In some embodiments, a composition comprises compound 281-A. In some embodiments, a composition comprises compound 281-B. In some embodiments, a composition comprises a mixture of compound 281-A and compound 281-B. In some embodiments, a composition comprises compound 282. In some embodiments, a composition comprises compound 282-A. In some embodiments, a composition comprises compound 282-B. 30 In some embodiments, a composition comprises a mixture of compound 282-A and compound 282-B. In some embodiments, the mixture comprises more than about 50% by weight or by mole fraction, more than about 55% by weight or by mole fraction, more than about 60% by weight or by mole fraction, more than about 65% by weight or by mole fraction, more than about 70% by weight or by mole fraction, more than about 75% by weight or by mole fraction, more than about 80% by weight or by mole fraction, more than about 85% by weight or by mole fraction, more than about 90% by weight or by mole fraction, more than about 91% by weight or by mole fraction, more than about 92% by weight or by mole fraction, more than about 93% by weight or 5 by mole fraction, more than about 94% by weight or by mole fraction, more than about 95% by weight or by mole fraction, more than about 96% by weight or by mole fraction, more than about 97% by weight or by mole fraction, more than about 98% by weight or by mole fraction, more than about 98.5% by weight or by mole fraction, more than about 99% by weight or by mole fraction, more than about 99.1% by weight or by mole fraction, more than about 99.2% by 10 weight or by mole fraction, more than about 99.3% by weight or by mole fraction, more than about 99.4% by weight or by mole fraction, more than about 99.5% by weight or by mole fraction, more than about 99.6% by weight or by mole fraction, more than about 99.7% by weight or by mole fraction, more than about 99.8% by weight or by mole fraction, more than about 99.9% by weight or by mole fraction, of one stereoisomer (e.g., atropisomer, enantiomer, 15 and / or diastereomer). In some embodiments, the compound is described in Example 2. In some embodiments, the compound is described in Example 3. In some embodiments, the compound is described in Example 4. In some embodiments, the compound is described in Example 5. In some embodiments, the compound is described in Example 6. In some embodiments, the compound is 20 described in Example 7. In some embodiments, the compound is described in Example 8. In some embodiments, the compound is described in Example 9. In some embodiments, the compound is described in Example 10. In some embodiments, the compound is described in Example 11. In some embodiments, the compound is described in Example 12. In some embodiments, the compound is described in Example 13. In some embodiments, the compound 25 is described in Example 14. In some embodiments, the compound is described in Example 15. In some embodiments, the compound is described in Example 16. In some embodiments, the compound is described in Example 17. In some embodiments, the compound is described in Example 18. In some embodiments, the compound is described in Example 19. In some embodiments, the compound is described in Example 20. In some embodiments, the compound 30 is described in Example 21. In some embodiments, the compound is described in Example 22. In some embodiments, the compound is described in Example 23. In some embodiments, the compound is described in Example 24. In some embodiments, the compound is described in Example 25. In some embodiments, the compound is described in Example 26. In some embodiments, the compound is described in Example 27. In some embodiments, the compound is described in Example 28. In some embodiments, the compound is described in Example 29. In some embodiments, the compound is described in Example 30. In some embodiments, the compound is described in Example 31. In some embodiments, the compound is described in Example 32. In some embodiments, the compound is described in Example 33. In some 5 embodiments, the compound is described in Example 34. In some embodiments, the compound is described in Example 35. In some embodiments, the compound is described in Example 36. In some embodiments, the compound is described in Example 37. In some embodiments, the compound is described in Example 38. In some embodiments, the compound is described in Example 39. In some embodiments, the compound is described in Example 40. In some 10 embodiments, the compound is described in Example 41. In some embodiments, the compound is described in Example 42. In some embodiments, the compound is described in Example 43. In some embodiments, the compound is described in Example 44. In some embodiments, the compound is described in Example 45. In some embodiments, the compound is described in Example 46. In some embodiments, the compound is described in Example 47. In some 15 embodiments, the compound is described in Example 48. In some embodiments, the compound is described in Example 49. In some embodiments, the compound is described in Example 50. In some embodiments, the compound is described in Example 51. In some embodiments, the compound is described in Example 52. In some embodiments, the compound is described in Example 53. In some embodiments, the compound is described in Example 54. In some 20 embodiments, the compound is described in Example 55. In some embodiments, the compound is described in Example 56. In some embodiments, the compound is described in Example 57. In some embodiments, the compound is described in Example 58. In some embodiments, the compound is described in Example 59. In some embodiments, the compound is described in Example 60. In some embodiments, the compound is described in Example 61. In some 25 embodiments, the compound is described in Example 62. In some embodiments, the compound is described in Example 63. In some embodiments, the compound is described in Example 64. In some embodiments, the compound is described in Example 65. In some embodiments, the compound is described in Example 66. In some embodiments, the compound is described in Example 67. In some embodiments, the compound is described in Example 68. In some 30 embodiments, the compound is described in Example 69. In some embodiments, the compound is described in Example 70. In some embodiments, the compound is described in Example 71. In some embodiments, the compound is described in Example 72. In some embodiments, the compound is described in Example 73. In some embodiments, the compound is described in Example 74. In some embodiments, the compound is described in Example 75. In some embodiments, the compound is described in Example 76. In some embodiments, the compound is described in Example 77. In some embodiments, the compound is described in Example 78. In some embodiments, the compound is described in Example 79. In some embodiments, the compound is described in Example 80. In some embodiments, the compound is described in 5 Example 81. In some embodiments, the compound is described in Example 82. In some embodiments, the compound is described in Example 83. In some embodiments, the compound is described in Example 84. In some embodiments, the compound is described in Example 85. In some embodiments, the compound is described in Example 86. In some embodiments, the compound is described in Example 87. In some embodiments, the compound is described in 10 Example 88. In some embodiments, the compound is described in Example 89. In some embodiments, the compound is described in Example 90. In some embodiments, the compound has a rotational energy barrier for interconversion between atropisomers of greater than about 25 kcal / mol. In some embodiments, the compound has a rotational energy barrier for interconversion between atropisomers of greater than about 28 15 kcal / mol. In some embodiments, the compound has a rotational energy barrier for interconversion between atropisomers of greater than about 30 kcal / mol. In some embodiments, the compound has a rotational energy barrier for interconversion between atropisomers of greater than about 33 kcal / mol. In some embodiments, the compound has a rotational energy barrier for interconversion between atropisomers of greater than about 35 kcal / mol. In some embodiments, 20 the compound has a rotational energy barrier for interconversion between atropisomers of greater than about 38 kcal / mol. In some embodiments, the compound has a rotational energy barrier for interconversion between atropisomers of greater than about 40 kcal / mol. In some embodiments, the compound has a half-life for interconversion between atropisomers of less than about 1 second. In some embodiments, the compound has a half-life 25 for interconversion between atropisomers of less than about 1.1 seconds. In some embodiments, the compound has a half-life for interconversion between atropisomers of less than about 1.2 seconds. In some embodiments, the compound has a half-life for interconversion between atropisomers of less than about 1.3 seconds. In some embodiments, the compound has a half-life for interconversion between atropisomers of less than about 1.4 seconds. In some embodiments, 30 the compound has a half-life for interconversion between atropisomers of less than about 1.5 seconds. In some embodiments, the compound has a half-life for interconversion between atropisomers of less than about 1.6 seconds. In some embodiments, the compound has a half-life for interconversion between atropisomers of less than about 1.7 seconds. In some embodiments, the compound has a half-life for interconversion between atropisomers of less than about 1.8 seconds. In some embodiments, the compound has a half-life for interconversion between atropisomers of less than about 1.9 seconds. In some embodiments, the compound has a half-life for interconversion between atropisomers of less than about 2 seconds. In some embodiments, the compound has a half-life for interconversion between 5 atropisomers of less than about 1 minute. In some embodiments, the compound has a half-life for interconversion between atropisomers of less than about 1 hour. In some embodiments, the compound has a half-life for interconversion between atropisomers of less than about 1 day. In some embodiments, the compound has a half-life for interconversion between atropisomers of less than about 1 week. In some embodiments, the compound has a half-life for interconversion 10 between atropisomers of less than about 1 month. In some embodiments, the compound has a half-life for interconversion between atropisomers of less than about 3 months. In some embodiments, the compound has a half-life for interconversion between atropisomers of less than about 6 months. In some embodiments, the compound has a half-life for interconversion between atropisomers of less than about 9 months. In some embodiments, the compound has a 15 half-life for interconversion between atropisomers of less than about 1 year. Disclosed herein, in some embodiments, is a process for providing a compound disclosed herein (e.g., a compound of Formula A, Formula B, or Formula C, or any subformula thereof, a compound of Table 1 or Table 2, or a compound described in the Examples, or a pharmaceutically acceptable salt thereof). 20 Pharmaceutical Compositions Compounds disclosed herein (e.g., compounds of Formula A, Formula B, or Formula C, or any subformula thereof, compounds of Table 1 or Table 2, and compounds described in the Examples, and a pharmaceutically acceptable salt thereof) are administered alone or as pharmaceutical compositions comprising the compounds disclosed herein and one or more 25 pharmaceutically acceptable excipients. Disclosed herein, in some embodiments, is a pharmaceutical composition comprising a compound disclosed herein (e.g., a compound of Formula A, Formula B, or Formula C, or any subformula thereof, a compound of Table 1 or Table 2, or a compound described in the Examples, or a pharmaceutically acceptable salt thereof) and a pharmaceutically acceptable 30 excipients (i.e., one or more pharmaceutically acceptable excipients). The compounds disclosed herein are used in free base forms, salt forms, or solvate forms, or as prodrugs. All forms are within the compositions (e.g., pharmaceutical compositions) described herein. The disclosed compounds, or salts, solvates, or prodrugs thereof, are administered to a subject in a variety of forms depending on the selected route of administration, as will be understood by those skilled in the art. The pharmaceutical compositions disclosed herein are be specially formulated for administration in solid or liquid form, including those adapted for the following routes of administration: oral, parenteral, buccal, intramuscular, 5 intraperitoneal, intrapulmonary, intrarectal, intrathecal, intratumoral, intravaginal, intravenous, nasal, ocular, subcutaneous, sublingual, transdermal, transepithelial, or transmucosal. Pharmaceutical compositions described herein are preferably formulated for administration to a subject (e.g., a human) in a biologically compatible form suitable for administration in vivo. Pharmaceutical compositions comprising compounds disclosed herein 10 (e.g., a compound of Formula A, Formula B, or Formula C, or any subformula thereof, a compound of Table 1 or Table 2, or a compound described in the Examples, or a pharmaceutically acceptable salt thereof) are useful for treating a disease, or symptoms thereof, described herein, such as cancer. The dosage of the compounds disclosed herein (e.g., compounds of Formula A, Formula 15 B, and Formula C, and any subformula thereof, compounds of Table 1 or Table 2, and compounds described in the Examples, and pharmaceutically acceptable salts thereof) in the pharmaceutical compositions, as well as the amount of the pharmaceutical composition administered to a subject, can vary depending on factors such characteristics of the subject (e.g., age, health, weight, and gender); the nature and extent of the symptoms; the frequency of 20 treatment; the mode of administration of the pharmaceutical compositions; the solubility of the compounds in the pharmaceutical compositions; the potency and activity of the compounds; and the pharmacodynamic properties of the compound. The dosage of the compounds disclosed here (e.g., compounds of Formula A, Formula B, and Formula C, and any subformula thereof, compounds of Table 1 or Table 2, and compounds described in the Examples, and 25 pharmaceutically acceptable salts thereof) or compositions comprising compounds disclosed herein are varied to achieve a desired therapeutic response for a particular subject, composition, or mode of administration, without being toxic to the subject. The present disclosure also provides kits including pharmaceutical compositions comprising compounds disclosed herein (e.g., compounds of Formula A, Formula B, and 30 Formula C, and any subformula thereof, compounds of Table 1 or Table 2, and compounds described in the Examples, and pharmaceutically acceptable salts thereof) and package inserts with instructions to perform any of the methods described herein. Disclosed herein, in some embodiments, is a process for providing a pharmaceutical composition comprising a compound disclosed herein (e.g., a compound of Formula A, Formula B, or Formula C, or any subformula thereof, a compound of Table 1 or Table 2, or a compound described in the Examples, or a pharmaceutically acceptable salt thereof). Methods of Treatment Compounds disclosed herein (e.g., compounds of Formula A, Formula B, or Formula C, 5 or any subformula thereof, compounds of Table 1 or Table 2, and compounds described in the Examples, and a pharmaceutically acceptable salt thereof) are useful for treating diseases. Compounds disclosed herein (e.g., compounds of Formula A, Formula B, or Formula C, or any subformula thereof, compounds of Table 1 or Table 2, and compounds described in the Examples, and a pharmaceutically acceptable salt thereof) are useful for modulating ferroptosis 10 (e.g., inducing ferroptosis). In some embodiments, the compounds are useful for treating ferroptosis-mediated diseases, such as cancer. In some embodiments, the compounds are useful for treating cancer. Disclosed herein, in some embodiments, is a method of treating a disease in a subject in need thereof, comprising administering to the subject an effective amount of a compound 15 disclosed herein (e.g., a compound of Formula A, Formula B, or Formula C, or any subformula thereof, a compound of Table 1 or Table 2, or a compound described in the Examples, or a pharmaceutically acceptable salt thereof) or a pharmaceutical composition comprising a compound disclosed herein (e.g., a compound of Formula A, Formula B, or Formula C, or any subformula thereof, a compound of Table 1 or Table 2, or a compound described in the 20 Examples, or a pharmaceutically acceptable salt thereof) and a pharmaceutically acceptable excipient. In some embodiments, the disease is cancer. Disclosed herein, in some embodiments, is a method of treating a ferroptosis-mediated disease in a subject in need thereof, comprising administering to the subject an effective amount of a compound disclosed herein (e.g., a compound of Formula A, Formula B, or Formula C, or 25 any subformula thereof, a compound of Table 1 or Table 2, or a compound described in the Examples, or a pharmaceutically acceptable salt thereof) or a pharmaceutical composition comprising a compound disclosed herein (e.g., a compound of Formula A, Formula B, or Formula C, or any subformula thereof, a compound of Table 1 or Table 2, or a compound described in the Examples, or a pharmaceutically acceptable salt thereof) and a pharmaceutically 30 acceptable excipient. In some embodiments, the ferroptosis-mediated disease is cancer. Disclosed herein, in some embodiments, is a compound disclosed herein (e.g., a compound of Formula A, Formula B, or Formula C, or any subformula thereof, a compound of Table 1 or Table 2, or a compound described in the Examples, or a pharmaceutically acceptable salt thereof) or a composition disclosed herein (e.g., a pharmaceutical composition comprising a compound disclosed herein (e.g., a compound of Formula A, Formula B, or Formula C, or any subformula thereof, a compound of Table 1 or Table 2, or a compound described in the Examples, or a pharmaceutically acceptable salt thereof) and a pharmaceutically acceptable 5 excipient), in the manufacture of a medicament for the treatment of a disease. In some embodiments, the disease is cancer. Disclosed herein, in some embodiments, is a compound disclosed herein (e.g., a compound of Formula A, Formula B, or Formula C, or any subformula thereof, a compound of Table 1 or Table 2, or a compound described in the Examples, or a pharmaceutically acceptable 10 salt thereof) or a composition disclosed herein (e.g., a pharmaceutical composition comprising a compound disclosed herein (e.g., a compound of Formula A, Formula B, or Formula C, or any subformula thereof, a compound of Table 1 or Table 2, or a compound described in the Examples, or a pharmaceutically acceptable salt thereof) and a pharmaceutically acceptable excipient), in the manufacture of a medicament for the treatment of a ferroptosis-mediated 15 disease. In some embodiments, the ferroptosis-mediated disease is cancer. The compounds disclosed herein (e.g., a compound of Formula A, Formula B, or Formula C, or any subformula thereof, a compound of Table 1 or Table 2, or a compound described in the Examples, or a pharmaceutically acceptable salt thereof) may be used in the form of free bases, salts, solvates, or prodrugs. All forms are within the methods described 20 herein. In some embodiments, the cancer is a metastatic cancer or a locally advanced cancer. In some embodiments, the cancer is a carcinoma, a leukemia, a lymphoma, a myeloma, a sarcoma, or a solid tumor cancer. In some embodiments, the sarcoma is fibrosarcoma. 25 In some embodiments, the cancer is a bladder cancer, a breast cancer, a colon cancer, a colorectal cancer, a gastric cancer (e.g., stomach cancer), a liver cancer, a lung cancer, an ovarian cancer, a pancreatic cancer, a prostate cancer, a renal cancer, a skin cancer, or a thyroid cancer. SELECTED EMBODIMENTS Embodiment 1. A compound of Formula A:10 or a pharmaceutically acceptable salt thereof, wherein: 5 each of X1, X2, X3, and X4is independently N or CR1; each of X5and X6is independently N or CR2; each instance of R1is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R1a, C2-20alkenyl optionally substituted with 1-4 instances of R1a, or C2-20alkynyl optionally substituted with 1-4 instances of R1a; 10 each instance of R1ais independently RB; each instance of R2is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R2a, C2-20alkenyl optionally substituted with 1-4 instances of R2a, or C2-20alkynyl optionally substituted with 1-4 instances of R2a; each instance of R2ais independently RB; 15 R3is C1-6alkyl, C1-6haloalkyl, C3-6carbocyclyl, or 3-6–membered heterocyclyl having 1- 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R3is optionally substituted with 1-6 instances of R3a; each R3ais independently halo, –CN, –NO2, C1-6alkyl, or C1-6alkoxy; each of R4and R5is independently H, halo, –CN, –NO2, C1-6alkyl, C1-6haloalkyl, or C3-620 carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3-6carbocyclylene; Ring A is C3-14carbocyclylene or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R6is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R6a, C2-20alkenyl optionally substituted with 1-4 instances of R6a, or C2-20alkynyl optionally substituted with 1-4 instances of R6a; each instance of R6ais independently RB; 5 L0is –O–, –NRL1–, –C(O)–, or –CRL2RL3–; L1is absent, –O–, –NRL1–, –C(O)–, or –CRL2RL3–; L2is absent, –O–, –NRL1–, or –CRL2RL3–; each instance of RL1is independently H or C1-6alkyl; each instance of RL2and RL3is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-610 carbocyclyl, or RL2and RL3are taken together with the atom to which each is attached to form C3-6carbocyclylene; R7is Ring B is C6-14aryl or 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 15 each instance of R8is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R8a, C2-20alkenyl optionally substituted with 1-4 instances of R8a, or C2-20alkynyl optionally substituted with 1-4 instances of R8a; each instance of R8ais independently RB; Y1is –C(O)– or –CRY1RY2–; 20 each instance of RY1and RY2is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-6carbocyclyl, or RY1and RY2are taken together with the atom to which each is attached to form C3-6carbocyclylene; Y2is absent or Ring D is C6-14arylene, C3-14carbocyclylene, 5-14–membered heteroarylene having 1-6 25 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R9is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R9a, C2-20alkenyl optionally substituted with 1-4 instances of R9a, or C2-20alkynyl 30 optionally substituted with 1-4 instances of R9a; each instance of R9ais independently RB; Y3is absent, –C(O)–, or –CRY1RY2–; each instance of RY1and RY2is independently H or C1-6alkyl; R10is H, halo, –CN, –NO2, –OH, –NH2, C1-6haloalkyl, C1-20alkyl, C1-20heteroalkyl, C2- 520alkenyl, C2-20alkynyl, or Ring E is C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R11is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 10 instances of R11a, C2-20alkenyl optionally substituted with 1-4 instances of R11a, or C2-20alkynyl optionally substituted with 1-4 instances of R11a; each instance of R11ais independently RB; each instance of RAis independently C1-6haloalkyl, halo, –CN, –NO2, –SF5, –C(O)Raa, – C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, – 15 S(O)2F, –S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, or –SRaa; each instance of RBis independently halo, –CN, –NO2, –SF5, –C(O)Raa, –C(O)ORaa, – C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, –S(O)2F, – S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, –SRaa, or –Si(Raa)3; each instance of Raais independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-2020 heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of Rbbis independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-20heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms 25 independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; m is 0, 1, 2, 3, 4, 5, or 6; n is 0, 1, 2, 3, 4, 5, or 6; o is 0, 1, 2, 3, 4, 5, or 6; and 30 p is 0, 1, 2, 3, 4, 5, or 6. Embodiment 2 A compound of Formula B: or a pharmaceutically acceptable salt thereof, each of X1, X2, X3, and X4is independently N or CR1; 5 each of X5and X6is independently N or CR2; each instance of R1is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R1a, C2-20alkenyl optionally substituted with 1-4 instances of R1a, or C2-20alkynyl optionally substituted with 1-4 instances of R1a; each instance of R1ais independently RB; 10 each instance of R2is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R2a, C2-20alkenyl optionally substituted with 1-4 instances of R2a, or C2-20alkynyl optionally substituted with 1-4 instances of R2a; each instance of R2ais independently RB; R3is C1-6alkyl, C1-6haloalkyl, C3-6carbocyclyl, or 3-6–membered heterocyclyl having 1- 15 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R3is optionally substituted with 1-6 instances of R3a; each R3ais independently halo, –CN, –NO2, C1-6alkyl, or C1-6alkoxy; each of R4and R5is independently H, halo, –CN, –NO2, C1-6alkyl, C1-6haloalkyl, or C3-6carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form 20 carbonyl or C3-6carbocyclylene; Ring A is C3-14carbocyclylene or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R6is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R6a, C2-20alkenyl optionally substituted with 1-4 instances of R6a, or C2-20alkynyl optionally substituted with 1-4 instances of R6a; each instance of R6ais independently RB; 5 L0is –NRL1–, –C(O)–, or –CRL2RL3–; L1is absent, –O–, –NRL1–, –C(O)–, or –CRL2RL3–; L2is absent, –O–, –NRL1–, or –CRL2RL3–; each instance of RL1is independently H or C1-6alkyl; each instance of RL2and RL3is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-610 carbocyclyl, or RL2and RL3are taken together with the atom to which each is attached to form C3-6carbocyclylene; R7is Ring B is C6-14aryl or 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 15 each instance of R8is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R8a, C2-20alkenyl optionally substituted with 1-4 instances of R8a, or C2-20alkynyl optionally substituted with 1-4 instances of R8a; each instance of R8ais independently RB; Y1is –C(O)– or –CRY1RY2–; 20 each instance of RY1and RY2is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-6carbocyclyl, or RY1and RY2are taken together with the atom to which each is attached to form C3-6carbocyclylene; Y2is absent or Ring D is C6- 14arylene, C3-14carbocyclylene, 5-14–membered heteroarylene having 1-6 25 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R9is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R9a, C2-20alkenyl optionally substituted with 1-4 instances of R9a, or C2-20alkynyl each instance of R9ais independently RB; Y3is absent, –C(O)–, or –CRY1RY2–; each instance of RY1and RY2is independently H or C1-6alkyl; R10is H, halo, –CN, –NO2, –OH, –NH2, C1-6haloalkyl, C1-20alkyl, C1-20heteroalkyl, C2- 520alkenyl, C2-20alkynyl, or Ring E is C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R11is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 10 instances of R11a, C2-20alkenyl optionally substituted with 1-4 instances of R11a, or C2-20alkynyl optionally substituted with 1-4 instances of R11a; each instance of R11ais independently RB; each instance of RAis independently C1-6haloalkyl, halo, –CN, –NO2, –SF5, –C(O)Raa, – C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, – 15 S(O)2F, –S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, or –SRaa; each instance of RBis independently halo, –CN, –NO2, –SF5, –C(O)Raa, –C(O)ORaa, – C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, –S(O)2F, – S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, –SRaa, or –Si(Raa)3; each instance of Raais independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-2020 heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of Rbbis independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-20heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms 25 independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; m is 0, 1, 2, 3, 4, 5, or 6; n is 0, 1, 2, 3, 4, 5, or 6; o is 0, 1, 2, 3, 4, 5, or 6; and 30 p is 0, 1, 2, 3, 4, 5, or 6. Embodiment 3 A compound of Formula C: or a pharmaceutically acceptable salt thereof, an atropisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof, 5 wherein: each of X1, X2, X3, and X4is independently N or CR1; each of X5and X6is independently N or CR2; each instance of R1is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R1a, C2-20alkenyl optionally substituted with 1-4 instances of R1a, or C2-20alkynyl 10 optionally substituted with 1-4 instances of R1a; each instance of R1ais independently RB; each instance of R2is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R2a, C2-20alkenyl optionally substituted with 1-4 instances of R2a, or C2-20alkynyl optionally substituted with 1-4 instances of R2a; 15 each instance of R2ais independently RB; R3is C1-6alkyl, C1-6haloalkyl, C3-6carbocyclyl, or 3-6–membered heterocyclyl having 1- 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R3is optionally substituted with 1-6 instances of R3a; each R3ais independently halo, –CN, –NO2, C1-6alkyl, or C1-6alkoxy; 20 each of R4and R5is independently H, halo, –CN, –NO2, C1-6alkyl, C1-6haloalkyl, or C3-6carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3-6carbocyclylene; Ring A is C3-14carbocyclylene or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R6is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R6a, C2-20alkenyl optionally substituted with 1-4 instances of R6a, or C2-20alkynyl optionally substituted with 1-4 instances of R6a; each instance of R6ais independently RB; 5 L0is –NRL1–, –C(O)–, or –CRL2RL3–; L1is absent, –O–, –NRL1–, –C(O)–, or –CRL2RL3–; L2is absent, –O–, –NRL1–, or –CRL2RL3–; each instance of RL1is independently H or C1-6alkyl; each instance of RL2and RL3is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-610 carbocyclyl, or RL2and RL3are taken together with the atom to which each is attached to form C3-6carbocyclylene; R7is Ring B is C6-14aryl or 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 15 each instance of R8is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R8a, C2-20alkenyl optionally substituted with 1-4 instances of R8a, or C2-20alkynyl optionally substituted with 1-4 instances of R8a; each instance of R8ais independently RB; Y1is –C(O)– or –CRY1RY2–; 20 each instance of RY1and RY2is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-6carbocyclyl, or RY1and RY2are taken together with the atom to which each is attached to form C3-6carbocyclylene; Y2is absent or Ring D is C6-14arylene, C3-14carbocyclylene, 5-14–membered heteroarylene having 1-6 25 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R9is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R9a, C2-20alkenyl optionally substituted with 1-4 instances of R9a, or C2-20alkynyl 30 optionally substituted with 1-4 instances of R9a; each instance of R9ais independently RB; Y3is absent, –C(O)–, or –CRY1RY2–; each instance of RY1and RY2is independently H or C1-6alkyl; R10is H, halo, –CN, –NO2, –OH, –NH2, C1-6haloalkyl, C1-20alkyl, C1-20heteroalkyl, C2- 520alkenyl, C2-20alkynyl, or Ring E is C - ary 614l, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R11is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 10 instances of R11a, C2-20alkenyl optionally substituted with 1-4 instances of R11a, or C2-20alkynyl optionally substituted with 1-4 instances of R11a; each instance of R11ais independently RB; each instance of RAis independently C1-6haloalkyl, halo, –CN, –NO2, –SF5, –C(O)Raa, – C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, – 15 S(O)2F, –S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, or –SRaa; each instance of RBis independently halo, –CN, –NO2, –SF5, –C(O)Raa, –C(O)ORaa, – C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, –S(O)2F, – S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, –SRaa, or –Si(Raa)3; each instance of Raais independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-2020 heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of Rbbis independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-20heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms 25 independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; m is 0, 1, 2, 3, 4, 5, or 6; n is 0, 1, 2, 3, 4, 5, or 6; o is 0, 1, 2, 3, 4, 5, or 6; and 30 p is 0, 1, 2, 3, 4, 5, or 6, provided that when each of X5and X6is CH; R3is ; each of R4and R5is H; Ring A is 5 L0is –C(O)–; L1is –CH2–; L2is –O–; R7is R8is halo; 10 Y1is –CRY1RY2–; Y2is absent or ; and Y3is absent or –CRY1RY2–, then R10is other than H, halo, 15 Embodiment 4. The compound of any one of embodiments 1 to 3, wherein X1is N. Embodiment 5. The compound of any one of embodiments 1 to 3, wherein X2is N. Embodiment 6. The compound of any one of embodiments 1 to 3, wherein X3is N. Embodiment 7. The compound of any one of embodiments 1 to 3, wherein X4is N. Embodiment 8. The compound of any one of embodiments 1 to 3, wherein X1is CR1, X220 is CR1, X3is CR1, and X4is CR1. Embodiment 9. The compound of any one of embodiments 1 to 8, wherein each instance of R1is independently H, RA, C1-12alkyl optionally substituted with 1-4 instances of R1a, C2-12alkenyl optionally substituted with 1-4 instances of R1a, or C2-12alkynyl optionally substituted with 1-4 instances of R1a. 5 Embodiment 10. The compound of any one of embodiments 1 to 8, wherein each instance of R1is independently R1is independently H, RA, or C2-20alkynyl optionally substituted with 1-4 instances of R1a. Embodiment 11. The compound of any one of embodiments 1 to 8, wherein each instance of R1is independently H, halo, –CN, –NO2, –C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or C2-20alkynyl 10 optionally substituted with 1-4 instances of R1a. Embodiment 12. The compound of any one of embodiments 1 to 8, wherein each instance of R1is independently H, halo, or C2-6alkynyl optionally substituted with 1-2 instances of R1a. Embodiment 13. The compound of any one of embodiments 1 to 8, wherein each instance of R1ais –Si(Raa)3. 15 Embodiment 14. The compound of any one of embodiments 1 to 13, wherein each instance of Raais independently C1-20alkyl, C6-14aryl, or C3-14carbocyclyl. Embodiment 15. The compound of any one of embodiments 1 to 13, wherein each instance of Raais independently –Me, –Et, –iPr, –Ph, or . Embodiment 16. The compound of any one of embodiments 1 to 13, wherein each instance 20 of Rbbis independently H or C1-20 alkyl. Embodiment 17. The compound of any one of embodiments 1 to 13, wherein each instance of Rbbis independently H, –Me, –Et, or –iPr. Embodiment 18. The compound of any one of embodiments 1 to 17, wherein each instance of R1is independently H, –F, –Cl, –Br, –C≡CSi(Raa)3, or –C≡CH. 25 Embodiment 19. The compound of any one of embodiments 1 to 17, wherein each instance of R1is independently H, –F, –Cl, –Br, –C≡CSi(CH3)3, or –C≡CH. Embodiment 20. The compound of any one of embodiments 1 to 17, wherein each instance of R1is –C≡CSi(CH3)3or –C≡CH. Embodiment 21. The compound of any one of embodiments 1 to 17, wherein each instance of R1is independently H, –F, –Cl, or –Br. 5 Embodiment 22. The compound of any one of embodiments 1 to 17, wherein each instance of R1is independently H, –F, or –Cl. Embodiment 23. The compound of any one of embodiments 1 to 22, wherein X5is N. Embodiment 24. The compound of any one of embodiments 1 to 22, wherein X6is N. Embodiment 25. The compound of any one of embodiments 1 to 22, wherein X5is CR2and 10 X6is CR2. Embodiment 26. The compound of any one of embodiments 1 to 25, wherein each instance of R2is independently H, RA, C1-12alkyl optionally substituted with 1-4 instances of R2a, C2-12alkenyl optionally substituted with 1-4 instances of R2a, or C2-12alkynyl optionally substituted with 1-4 instances of R2a. 15 Embodiment 27. The compound of any one of embodiments 1 to 25, wherein each instance of R2is independently H, RA, C1-6alkyl optionally substituted with 1-4 instances of R2a, C2-6alkenyl optionally substituted with 1-4 instances of R2a, or C2-6alkynyl optionally substituted with 1-4 instances of R2a. Embodiment 28. The compound of any one of embodiments 1 to 25, wherein each instance 20 of R2is independently H, halo, –CN, –NO2, –C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or C2-20alkynyl optionally substituted with 1-4 instances of R2a. Embodiment 29. The compound of any one of embodiments 1 to 25, wherein each instance of R2is independently H, halo, –CN, –NO2, –C(O)Raa, –N(Rbb)2, –ORaa, or –SRaa. Embodiment 30. The compound of any one of embodiments 1 to 25, wherein each instance 25 of R2is independently H or halo. Embodiment 31. The compound of any one of embodiments 1 to 25, wherein each instance of R2is independently H or F Embodiment 32. The compound of any one of embodiments 1 to 31, wherein R3is C1-6alkyl, C1-6haloalkyl, C3-6carbocyclyl, or 3-6–membered heterocyclyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. Embodiment 33. The compound of any one of embodiments 1 to 31, wherein R3is C1-65 alkyl, C1-6haloalkyl, C3-6carbocyclyl, or 3-6–membered heterocyclyl having 1 heteroatom selected from nitrogen and oxygen. Embodiment 34. The compound of any one of embodiments 1 to 31, wherein R3is –Me, – Et, –nPr, –iPr, –nBu, –iBu, –sBu, –tBu, –(CH2)4CH3, –(CH2)5CH6, –CH2F, –CHF2, –CF3, – CH2CF3, –CH(CF3)2, –CF2CF3, –CH(CF3)(CF2OCH3), cyclopropyl, , cyclobutyl, 10 cyclopentyl, cyclohexyl, or Embodiment 35. The compound of any one of embodiments 1 to 31, wherein R3is –Me, – Et, –nPr, –iPr, –CH2F, –CHF2, –CF3, –CH2CF3, –CH(CF3)2, –CF2CF3, –CH(CF3)(CF2OCH3), cyclopropyl, , cyclobutyl, or Embodiment 36. The compound of any one of embodiments 1 to 31, wherein R3is –iPr or – 15 CH2CF3. Embodiment 37. The compound of any one of embodiments 1 to 31, wherein R3is –iPr. Embodiment 38. The compound of any one of embodiments 1 to 31, wherein R3is – CH2CF3. Embodiment 39. The compound of any one of embodiments 1 to 31, wherein R4is H, halo, 20 C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, or C3-6carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3-6carbocyclylene. Embodiment 40. The compound of any one of embodiments 1 to 38, wherein R4is H, halo, C1-3alkyl, C1-3haloalkyl, or C3-4carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3 4carbocyclylene Embodiment 41. The compound of any one of embodiments 1 to 38, wherein R4is H, –F, – Cl, , –CN, –NO2, –OH, –Me, –Et, –iPr, –tBu, –CF3, –OMe, –OEt, –OiPr, –OtBu,4 , or R and R5are taken together with the atom to which each is attached to form carbonyl or cyclopropylene ring. 5 Embodiment 42. The compound of any one of embodiments 1 to 38, wherein R4is H, –F, – Cl, –Me, –Et, –CF3, or4 5 , or R and R are taken together with the atom to which each is attached to form carbonyl or cyclopropylene ring. Embodiment 43. The compound of any one of embodiments 1 to 38, wherein R4is H, –F, – Me, –CF3, or or R4and R5are taken together with the atom to which each is attached to 10 form carbonyl or cyclopropylene ring. Embodiment 44. The compound of any one of embodiments 1 to 43, wherein R5is H, halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, or C3-6carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3-6carbocyclylene. Embodiment 45. The compound of any one of embodiments 1 to 43, wherein R5is H, halo, 15 C1-3 alkyl, C1-3 haloalkyl, or C3-4 carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3-4carbocyclylene. Embodiment 46. The compound of any one of embo embodiments 1 to 43, wherein R5is H, –F, –Cl, , –CN, –NO2, –OH, –Me, –Et, –iPr, –tBu, –CF3, –OMe, –OEt, –OiPr, –OtBu, or 45 R and R are taken together with the atom to which each is attached to form carbonyl or 20 cyclopropylene ring. Embodiment 47. The compound of any one of embodiments 1 to 43, wherein R5is H, –F, – Cl, –Me, –Et, –CF3, or or R4and R5are taken together with the atom to which each is attached to form carbonyl or cyclopropylene ring. Embodiment 48. The compound of any one of embodiments 1 to 43, wherein R5is H, –F, – 25 Me, –CF3, or or R4and R5are taken together with the atom to which each is attached to form carbonyl or cyclopropylene ring. Embodiment 49. The compound of any one of embodiments 1 to 48, wherein Ring A is C3- 10carbocyclylene or 3-10–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. Embodiment 50. The compound of any one of embodiments 1 to 48, wherein Ring A is C3- 510carbocyclylene. Embodiment 51. The compound of any one of embodiments 1 to 48, wherein Ring A is 3- 10–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. Embodiment 52. The compound of any one of embodiments 1 to 48, wherein Ring A is C3-810 carbocyclylene. Embodiment 53. The compound of any one of embodiments 1 to 48, wherein Ring A is 3- 8–membered heterocyclylene having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. Embodiment 54. The compound of any one of embodiments 1 to 48, wherein Ring A is 3- 15 5–membered heterocyclylene having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. Embodiment 55. The compound of any one of embodiments 1 to 48, wherein Ring A is 6– membered heterocyclylene having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. 20 Embodiment 56. The compound of any one of embodiments 1 to 48, wherein Ring A is 7- 10–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. Embodiment 57. The compound any one of embodiments 1 to 56, wherein Ring A is monocyclic. 25 Embodiment 58. The compound any one of embodiments 1 to 56, wherein Ring A is polycyclic. Embodiment 59. The compound any one of embodiments 1 to 56, wherein Ring A is a spirocyclic or bridged ring system. Embodiment 60. The compound any one of embodiments 1 to 56, wherein Ring A is a fused ring system. Embodiment 61. The compound any one of embodiments 1 to 56, wherein Ring A is saturated. 5 Embodiment 62. The compound any one of embodiments 1 to 56, wherein Ring A is partially unsaturated. Embodiment 63. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is selected from: 10 , , , , Embodiment 64. The compound of any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is selected from: 5 Embodiment 65. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is 10 Embodiment 66. The compound any one of embodiments 1 to 56, wherein Ring A together s Embodiment 67. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is Embodiment 68. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is 5 Embodiment 69. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is Embodiment 70. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is Embodiment 71. The compound any one of embodiments 1 to 56, wherein Ring A together 10 with its R6substituents is Embodiment 72. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is Embodiment 73. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is Embodiment 74. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents i 5 Embodiment 75. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is Embodiment 76. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents i Embodiment 77. The compound any one of embodiments 1 to 56, wherein Ring A together 10 with its R6substituents is Embodiment 78. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is Embodiment 79. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is Embodiment 80. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is 5 Embodiment 81. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is Embodiment 82. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is Embodiment 83. The compound any one of embodiments 1 to 56, wherein Ring A together 10 with its R6substituents is Embodiment 84. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is Embodiment 85. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is Embodiment 86. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is 5 Embodiment 87. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is Embodiment 88. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is Embodiment 89. The compound any one of embodiments 1 to 56, wherein Ring A together 10 with its R6substituents is Embodiment 90. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is Embodiment 91. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is Embodiment 92. The compound of any one of embodiments 1 to 91, wherein each instance of R6is independently oxo, RA, C1-12alkyl optionally substituted with 1-4 instances of R6a, C2-125 alkenyl optionally substituted with 1-4 instances of R6a, or C2-12alkynyl optionally substituted with 1-4 instances of R6a. Embodiment 93. The compound of any one of embodiments 1 to 91, wherein each instance of R6is independently oxo, RA, C1-6alkyl optionally substituted with 1-4 instances of R6a, C2-6alkenyl optionally substituted with 1-4 instances of R6a, or C2-6alkynyl optionally substituted 10 with 1-4 instances of R6a. Embodiment 94. The compound of any one of embodiments 1 to 91, wherein each instance of R6is independently oxo, RAor C1-20alkyl optionally substituted with 1-4 instances of R6a. Embodiment 95. The compound of any one of embodiments 1 to 91, wherein each instance of R6is independently oxo, C1-6haloalkyl, halo, –CN, –NO2, –C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, 15 or C1-20alkyl optionally substituted with 1-4 instances of R6a. Embodiment 96. The compound of any one of embodiments 1 to 91, wherein each instance of R6is independently C1-6haloalkyl, halo, –ORaa, or C1-20alkyl optionally substituted with 1-4 instances of R6a. Embodiment 97. The compound of any one of embodiments 1 to 91, wherein each instance20 of R6is independently –CH2F, –CHF2, –CF3, –CH2CF3, –CH(CF3)2, –CF2CF3, –F, –Cl, –Br, – OH, –OMe, –OEt, –OiPr, –OtBu, –Me, –Et, –nPr, –iPr, –nBu, –iBu, –sBu, –tBu, –(CH2)4CH3, or –(CH2)5CH6. Embodiment 98. The compound of any one of embodiments 1 to 91, wherein each instance of R6is –CH2F, –CHF2, –CF3, –CH2CF3, –CH(CF3)2, –CF2CF3, –OH, –OMe, –OEt, –Me, or –Et. 25 Embodiment 99. The compound of any one of embodiments 1 to 91, wherein each instance of R6is CHF OH or Me Embodiment 100. The compound of any one of embodiments 1 to 99, wherein m is 0, 1, 2, or 3. Embodiment 101. The compound of any one of embodiments 1 to 99, wherein is 1, 2, or 3. Embodiment 102. The compound of any one of embodiments 1 to 99, wherein m is 0. 5 Embodiment 103. The compound of any one of embodiments 1 to 99, wherein m is 1. Embodiment 104. The compound of any one of embodiments 1 to 99, wherein m is 2. Embodiment 105. The compound of any one of embodiments 1 to 99, wherein m is 3. Embodiment 106. The compound any one of embodiments 1 to 56, wherein Ring A together with its R6substituents is selected from: Embodiment 107. The compound of any one of embodiments 1 to 56, wherein Ring A is 15 Embodiment 108. The compound of any one of embodiments 1 to 107, wherein L0is – NRL1–, –C(O)–, or –CRL2RL3–. Embodiment 109. The compound of any one of embodiments 1 to 108, wherein L1is – NRL1–, –C(O)–, or –CRL2RL3–. Embodiment 110. The compound of any one of embodiments 1 to 109, wherein L2is –O– or 20 –CRL2RL3–. Embodiment 111. The compound of any one of embodiments 1 to 110, wherein each instance of RL1is independently H, –Me, –Et, –nPr, –iPr, –nBu, –iBu, –sBu, –tBu, –(CH2)4CH3, –(CH2)5CH6. Embodiment 112. The compound of any one of embodiments 1 to 110, wherein each 5 instance of RL1is independently H, –Me, –Et, or –iPr. Embodiment 113. The compound of any one of embodiments 1 to 110, wherein each instance of RL1is independently H or –Me. Embodiment 114. The compound of any one of embodiments 1 to 113, wherein RL2is H, –F, –Cl, –Br, –Me, –Et, –nPr, –iPr, –nBu, –iBu, –sBu, –tBu, –(CH2)4CH3, –(CH2)5CH6, cyclopropyl, 10 cyclobutyl, cyclopentyl, or cyclohexyl, or RL2and RL3are taken together to form cyclopropylene, cyclobutylene, cyclopentylene, or cyclohexylene. Embodiment 115. The compound of any one of embodiments 1 to 113, wherein RL2is H, –F, –Cl, –Me, –Et, –iPr, cyclopropyl, or cyclobutylene, or RL2and RL3are taken together to form cyclopropylene or cyclobutylene. 15 Embodiment 116. The compound of any one of embodiments 1 to 113, wherein RL2is H,– Me, or cyclopropyl, or RL2and RL3are taken together to form cyclopropylene. Embodiment 117. The compound of any one of embodiments 1 to 113, wherein RL2is H or – Me. Embodiment 118. The compound of any one of embodiments 1 to 117, wherein RL3is H, –F, 20 –Cl, –Br, –Me, –Et, –nPr, –iPr, –nBu, –iBu, –sBu, –tBu, –(CH2)4CH3, –(CH2)5CH6, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, or RL2and RL3are taken together to form cyclopropylene, cyclobutylene, cyclopentylene, or cyclohexylene. Embodiment 119. The compound of any one of embodiments 1 to 117, wherein RL3is H, –F, –Cl, –Me, –Et, –iPr, cyclopropyl, or cyclobutylene, or RL2and RL3are taken together to form 25 cyclopropylene or cyclobutylene. Embodiment 120. The compound of any one of embodiments 1 to 117, wherein RL3is H,– Me, or cyclopropyl, or RL2and RL3are taken together to form cyclopropylene. Embodiment 121. The compound of any one of embodiments 1 to 117, wherein RL3is H or – Me. Embodiment 122. The compound of any one of embodiments 1 to 121, wherein L0is –NH–, –C(O)–, or –CH2–. 5 Embodiment 123. The compound of any one of embodiments 1 to 121, wherein L0is – C(O)–. Embodiment 124. The compound of any one of embodiments 1 to 123, wherein L1is –NH–, –NCH3–, –C(O)–, –CH2–, or –CH(CH3)–. Embodiment 125. The compound of any one of embodiments 1 to 123, wherein L1is –NH–, 10 –NCH3–, –CH2–, or –CH(CH3)–. Embodiment 126. The compound of any one of embodiments 1 to 123, wherein L1is –NH–, –NCH3–, –CH2–, or –CH(CH3)–. Embodiment 127. The compound of any one of embodiments 1 to 123, wherein L1is –NH– or –NCH3–. 15 Embodiment 128. The compound of any one of embodiments 1 to 123, wherein L1is –CH2– or –CH(CH3)–. Embodiment 129. The compound of any one of embodiments 1 to 123, wherein L1is absent. Embodiment 130. The compound of any one of embodiments 1 to 129, wherein L2is –O– or –CRL2RL3–. 20 Embodiment 131. The compound of any one of embodiments 1 to 129, wherein L2is –O–, – CH2–, or –CH(CH3)–. Embodiment 132. The compound of any one of embodiments 1 to 129, wherein L2is –O–. Embodiment 133. The compound of any one of embodiments 1 to 129, wherein L2is –CH2– or –CH(CH3)–. 25 Embodiment 134. The compound of any one of embodiments 1 to 129, wherein L2is absent. Embodiment 135. The compound of any one of embodiments 1 to 134, wherein Ring B is C6-14aryl. Embodiment 136. The compound of any one of embodiments 1 to 134, wherein Ring B is C6-10aryl. 5 Embodiment 137. The compound of any one of embodiments 1 to 134, wherein Ring B is C6aryl. Embodiment 138. The compound of any one of embodiments 1 to 134, wherein Ring B is 5- 14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. 10 Embodiment 139. The compound of any one of embodiments 1 to 134, wherein Ring B is 5- 10–membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. Embodiment 140. The compound of any one of embodiments 1 to 134, wherein Ring B is 5- 6–membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, 15 and sulfur. Embodiment 141. The compound of any one of embodiments 1 to 134, wherein Ring B is 5- 6–membered heteroaryl having 1-4 nitrogen atoms. Embodiment 142. The compound of any one of embodiments 1 to 134, wherein R7is selected from: 2 Embodiment 143. The compound of any one of embodiments 1 to 134, wherein R7is Embodiment 144. The compound of any one of embodiments 1 to 134, wherein R7is 5 Embodiment 145. The compound of any one of embodiments 1 to 134, wherein R7is Embodiment 146. The compound of any one of embodiments 1 to 134, wherein R7is Embodiment 147. The compound of any one of embodiments 1 to 134, wherein R7is 10 Embodiment 148. The compound of any one of embodiments 1 to 134, wherein R7is Embodiment 149. The compound of any one of embodiments 1 to 134, wherein R7is 15 Embodiment 150. The compound of any one of embodiments 1 to 134, wherein R7is Embodiment 151. The compound of any one of embodiments 1 to 134, wherein R7is Embodiment 152. The compound of any one of embodiments 1 to 134, wherein R7is 5 Embodiment 153. The compound of any one of embodiments 1 to 134, wherein R7is Embodiment 154. The compound of any one of embodiments 1 to 134, wherein R7is selected from:10 Embodiment 155. The compound of any one of embodiments 1 to 134, wherein R7 is Embodiment 156. The compound of any one of embodiments 1 to 134, wherein R7 is 15 Embodiment 157. The compound of any one of embodiments 1 to 134, wherein R7 is Embodiment 158. The compound of any one of embodiments 1 to 134, wherein R7 is Embodiment 159. The compound of any one of embodiments 1 to 134, wherein R7is 5 Embodiment 160. The compound of any one of embodiments 1 to 134, wherein R7is Embodiment 161. The compound of any one of embodiments 1 to 134, wherein R7is Embodiment 162. The compound of any one of embodiments 1 to 134, wherein R7is10 Embodiment 163. The compound of any one of embodiments 1 to 134, wherein R7is Embodiment 164. The compound of any one of embodiments 1 to 134, wherein R7is 15 Embodiment 165. The compound of any one of embodiments 1 to 134, wherein R7is Embodiment 166. The compound of any one of embodiments 1 to 165, wherein each instance of R8is independently oxo, RA, C1-12alkyl optionally substituted with 1-4 instances of R8a, C2-12alkenyl optionally substituted with 1-4 instances of R8a, or C2-12alkynyl optionally substituted with 1-4 instances of R8a5 Embodiment 167. The compound of any one of embodiments 1 to 165, wherein each instance of R8is independently oxo, RA, or C1-20alkyl optionally substituted with 1-4 instances of R8aEmbodiment 168. The compound of any one of embodiments 1 to 165, wherein each instance of R8is independently oxo, C1-6haloalkyl, halo, –CN, –NO2, –C(O)Raa, –N(Rbb)2, – 10 ORaa, –SRaa, or C1-20alkyl optionally substituted with 1-4 instances of R8a. Embodiment 169. The compound of any one of embodiments 1 to 165, wherein each instance of R8is independently oxo, C1-6haloalkyl, halo, –CN, –NO2, –C(O)Raa, –N(Rbb)2, – ORaa, –SRaa, or C1-20alkyl. Embodiment 170. The compound of any one of embodiments 1 to 165, wherein each 15 instance of R8is independently oxo, C1-6haloalkyl, halo, –CN, –NO2, or C1-6alkyl. Embodiment 171. The compound of any one of embodiments 1 to 165, wherein each instance of R8is independently oxo, –CH2F, –CHF2, –CF3, –CH2CF3, –CH(CF3)2, –CF2CF3, –F, –Cl, –Br, –CN, –NO2, –Me, –Et, –nPr, –iPr, –nBu, –iBu, –sBu, –tBu, –(CH2)4CH3, –(CH2)5CH6. Embodiment 172. The compound of any one of embodiments 1 to 165, wherein each 20 instance of R8is independently oxo, –CH2F, –CHF2, –CF3, –CH2CF3, –CH(CF3)2, –CF2CF3, –F, –Cl, –CN, –NO2, –Me, or –Et. Embodiment 173. The compound of any one of embodiments 1 to 165, wherein each instance of R8is independently oxo, –CH2F, –CHF2, –CF3, –F, –Cl, –CN, –NO2, or –Me. Embodiment 174. The compound of any one of embodiments 1 to 165, wherein each 25 instance of R8is independently oxo, –CF3, –Cl, or –CN. Embodiment 175. The compound of any one of embodiments 1 to 174, wherein n is 0, 1, 2, or 3. Embodiment 176. The compound of any one of embodiments 1 to 174, wherein n is 1, 2, or 3. Embodiment 177. The compound of any one of embodiments 1 to 174, wherein n is 1. Embodiment 178. The compound of any one of embodiments 1 to 174, wherein n is 2. 5 Embodiment 179. The compound of any one of embodiments 1 to 174, wherein n is 3. Embodiment 180. The compound of any one of embodiments 1 to 174, wherein n is 0. Embodiment 181. The compound of any one of embodiments 1 to 180, wherein R7is selected from:1 Embodiment 182. The compound of any one of embodiments 1 to 180, wherein Y1is – C(O)–. Embodiment 183. The compound of any one of embodiments 1 to 180, wherein Y1is – CRY1RY2–. 15 Embodiment 184. The compound of any one of embodiments 1 to 183, wherein Y3is absent. Embodiment 185. The compound of any one of embodiments 1 to 183, wherein Y3is – Embodiment 186. The compound of any one of embodiments 1 to 185, wherein RY1is H, –F, –Cl, –Br, –Me, –Et, –nPr, –iPr, –nBu, –iBu, –sBu, –tBu, –(CH2)4CH3, –(CH2)5CH6, cyclopropyl, 20 cyclobutyl, cyclopentyl, or cyclohexyl, or RY1and RY2are taken together with the atom to which each is attached to form carbonyl, cyclopropylene, cyclobutylene, cyclopentylene, or cyclohexylene. Embodiment 187. The compound of any one of embodiments 1 to 185, wherein RY1is H, –F, –Cl, –Me, –Et, –iPr, cyclopropyl, or cyclobutylene, or RY1and RY2are taken together with the atom to which each is attached to form carbonyl, cyclopropylene, or cyclobutylene Embodiment 188. The compound of any one of embodiments 1 to 185, wherein RY1is H,– 5 Me, or cyclopropyl, or RY1and RY2are taken together with the atom to which each is attached to form carbonyl or cyclopropylene. Embodiment 189. The compound of any one of embodiments 1 to 185, wherein RY1is H or – Me. Embodiment 190. The compound of any one of embodiments 1 to 189, wherein RY2is H, –F, 10 –Cl, –Br, –Me, –Et, –nPr, –iPr, –nBu, –iBu, –sBu, –tBu, –(CH2)4CH3, –(CH2)5CH6, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, or RY1and RY2are taken together with the atom to which each is attached to form carbonyl, cyclopropylene, cyclobutylene, cyclopentylene, or cyclohexylene. Embodiment 191. The compound of any one of embodiments 1 to 189, wherein RY2is H, –F, 15 –Cl, –Me, –Et, –iPr, cyclopropyl, or cyclobutylene, or RY1and RY2are taken together with the atom to which each is attached to form carbonyl, cyclopropylene, or cyclobutylene. Embodiment 192. The compound of any one of embodiments 1 to 189, wherein RY2is H,– Me, or cyclopropyl, or RY1and RY2are taken together with the atom to which each is attached to form carbonyl or cyclopropylene. 20 Embodiment 193. The compound of any one of embodiments 1 to 189, wherein RY2is H or – Me. Embodiment 194. The compound of any one of embodiments 1 to 193, wherein Y1is – C(O)–, –CH2–, or –CH(CH3)–. Embodiment 195. The compound of any one of embodiments 1 to 193, wherein Y1is –CH2– 25 or –CH(CH3)–. Embodiment 196. The compound of any one of embodiments 1 to 193, wherein Y1is –CH2–. Embodiment 197. The compound of any one of embodiments 1 to 196, wherein Y3is absent, –CH2–, or –CH(CH3)–. Embodiment 198. The compound of any one of embodiments 1 to 196, wherein Y3is –CH2– or –CH(CH3)–. Embodiment 199. The compound of any one of embodiments 1 to 196, wherein Y3is –CH2–. Embodiment 200. The compound of any one of embodiments 1 to 199, wherein Y2is absent. 5 Embodiment 201. The compound of any one of embodiments 1 to 199, wherein Y2is Embodiment 202. The compound of any one of embodiments 1 to 201, wherein Ring D is C6-14arylene, C3-14carbocyclylene, 5-14–membered heteroarylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclylene 10 having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. Embodiment 203. The compound of any one of embodiments 1 to 201, wherein Ring D is C6-10arylene, C3-10carbocyclylene, 5-10–membered heteroarylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-10–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. 15 Embodiment 204. The compound of any one of embodiments 1 to 201, wherein Ring D is C6arylene, C3-8carbocyclylene, 5-6–membered heteroarylene having 1-4 heteroatoms independently selected from nitrogen and oxygen, or 3-8–membered heterocyclylene having 1-4 heteroatoms independently selected from nitrogen and oxygen. Embodiment 205. The compound of any one of embodiments 1 to 201, wherein Ring D is 20 C3-8carbocyclylene or 3-8–membered heterocyclylene having 1-4 heteroatoms independently selected from nitrogen and oxygen. Embodiment 206. The compound of any one of embodiments 1 to 201, wherein Ring D is 3- 8–membered heterocyclylene having 1-4 heteroatoms independently selected from nitrogen and oxygen Embodiment 207. The compound of any one of embodiments 1 to 201, wherein Ring D together with its R9substituents is Embodiment 208. The compound of any one of embodiments 1 to 201, wherein Ring D together with its R9substituents is 5 Embodiment 209. The compound of any one of embodiments 1 to 208, wherein each instance of R9is independently oxo, RA, C1-6haloalkyl, C1-20alkyl optionally substituted with 1-2 instances of R9a, C2-20alkenyl optionally substituted with 1-2 instances of R9a, or C2-20alkynyl optionally substituted with 1-2 instances of R9a. Embodiment 210. The compound of any one of embodiments 1 to 208, wherein each10 instance of R9is independently –CH2F, –CHF2, –CF3, –CH2CF3, –CH(CF3)2, –CF2CF3, –F, –Cl, – Br, –OH, –OMe, –OEt, –OiPr, –OtBu, –Me, –Et, –nPr, –iPr, –nBu, –iBu, –sBu, –tBu, – (CH2)4CH3, or –(CH2)5CH6. Embodiment 211. The compound of any one of embodiments 1 to 210, wherein o is 0, 1, 2, or 3. 15 Embodiment 212. The compound of any one of embodiments 1 to 210, wherein o is 1, 2, or 3. Embodiment 213. The compound of any one of embodiments 1 to 210, wherein o is 1. Embodiment 214. The compound of any one of embodiments 1 to 210, wherein o is 2. Embodiment 215. The compound of any one of embodiments 1 to 210, wherein o is 3. 20 Embodiment 216. The compound of any one of embodiments 1 to 210, wherein o is 0. Embodiment 217. The compound of any one of embodiments 1 to 216, wherein R10is H, halo, –CN, –NO2, –OH, –NH2, C1-6haloalkyl, C1-20alkyl, C1-20heteroalkyl, C2-20alkenyl, or C2- 20alkynyl. Embodiment 218. The compound of any one of embodiments 1 to 216, wherein R10is H, halo, –CN, –NO2, –OH, –NH2, C1-6haloalkyl, C1-20alkyl, C1-12heteroalkyl, C2-12alkenyl, or C2- 12alkynyl. Embodiment 219. The compound of any one of embodiments 1 to 216, wherein R10is H, 5 halo, –CN, –NO2, –OH, –NH2, C1-6alkyl, C1-6haloalkyl, C1-6heteroalkyl, C2-6alkenyl, or C2-6alkynyl. Embodiment 220. The compound of any one of embodiments 1 to 216, wherein R10is H, –F, or –OH. Embodiment 221. The compound of any one of embodiments 1 to 216, wherein R10is 10 Embodiment 222. The compound of any one of embodiments 1 to 221, wherein Ring E is C6-10aryl, C3-10carbocyclyl, 5-10–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-10–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. 15 Embodiment 223. The compound of any one of embodiments 1 to 221, wherein Ring E is C6-8aryl, C3-10carbocyclyl, 5-8–membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-8–membered heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. Embodiment 224. The compound of any one of embodiments 1 to 221, wherein Ring E is 20 C3-10carbocyclyl or 3-8–membered heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. Embodiment 225. The compound any one of embodiments 1 to 224, wherein Ring E is a spirocyclic or bridged ring system. Embodiment 226. The compound any one of embodiments 1 to 224, wherein Ring E is 25 saturated. Embodiment 227. The compound any one of embodiments 1 to 224, wherein Ring E is Embodiment 228. The compound of any one of embodiments 1 to 221, wherein Ring E is C6-8aryl or 5-8–membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. Embodiment 229. The compound any one of embodiments 1 to 228, wherein Ring E is 5 monocyclic. Embodiment 230. The compound any one of embodiments 1 to 228, wherein Ring E is polycyclic. Embodiment 231. The compound any one of embodiments 1 to 228, wherein Ring E is a fused ring system 10 Embodiment 232. The compound of any one of embodiments 1 to 221, wherein R10is selected from: Embodiment 233. The compound of any one of embodiments 1 to 221, wherein R10is Embodiment 234. The compound of any one of embodiments 1 to 221, wherein R10is Embodiment 235. The compound of any one of embodiments 1 to 221, wherein R10is 5 Embodiment 236. The compound of any one of embodiments 1 to 221, wherein R10is Embodiment 237. The compound of any one of embodiments 1 to 221, wherein R10is Embodiment 238. The compound of any one of embodiments 1 to 221, wherein R10is 10 Embodiment 239. The compound of any one of embodiments 1 to 221, wherein R10is Embodiment 240. The compound of any one of embodiments 1 to 221, wherein R10is 15 Embodiment 241. The compound of any one of embodiments 1 to 221, wherein R10is Embodiment 242. The compound of any one of embodiments 1 to 221, wherein R10is Embodiment 243. The compound of any one of embodiments 1 to 221, wherein R10is 5 Embodiment 244. The compound of any one of embodiments 1 to 221, wherein R10is Embodiment 245. The compound of any one of embodiments 1 to 221, wherein R10is Embodiment 246. The compound of any one of embodiments 1 to 221, wherein R10is 10 Embodiment 247. The compound of any one of embodiments 1 to 221, wherein R10is Embodiment 248. The compound of any one of embodiments 1 to 221, wherein R10is 15 Embodiment 249. The compound of any one of embodiments 1 to 221, wherein R10is Embodiment 250. The compound of any one of embodiments 1 to 221, wherein R10is Embodiment 251. The compound of any one of embodiments 1 to 221, wherein R10is 5 Embodiment 252. The compound of any one of embodiments 1 to 221, wherein R10is Embodiment 253. The compound of any one of embodiments 1 to 221, wherein R10is Embodiment 254. The compound of any one of embodiments 1 to 221, wherein R10is 10 Embodiment 255. The compound of any one of embodiments 1 to 221, wherein R10is Embodiment 256. The compound of any one of embodiments 1 to 221, wherein R10is 15 Embodiment 257. The compound of any one of embodiments 1 to 221, wherein R10is Embodiment 258. The compound of any one of embodiments 1 to 221, wherein R10is Embodiment 259. The compound of any one of embodiments 1 to 258, wherein each instance of R11is independently oxo, RA, C1-20alkyl optionally substituted with 1-2 instances of 5 R11a, C2-20alkenyl optionally substituted with 1-2 instances of R11a, or C2-20alkynyl optionally substituted with 1-2 instances of R11a. Embodiment 260. The compound of any one of embodiments 1 to 258, wherein each instance of R11is independently oxo, C1-6haloalkyl, halo, –CN, –NO2, –C(O)Raa, –N(Rbb)2, – ORaa, –SRaa, or C1-20 alkyl optionally substituted with 1-4 instances of R11a. 10 Embodiment 261. The compound of any one of embodiments 1 to 258, wherein each instance of R11is independently C1-6haloalkyl, halo, –ORaa, –C(O)Raa, or C1-20alkyl optionally substituted with 1-4 instances of R11a. Embodiment 262. The compound of any one of embodiments 1 to 258, wherein each instance of R11is independently –CH2F, –CHF2, –CF3, –CH2CF3, –CH(CF3)2, –CF2CF3, –F, –Cl, 15 –Br, –OH, –OMe, –OEt, –OiPr, –OtBu, –C(O)(CH2)0-18(CH3), –C(O)(CH2)1-8(C=C)(CH2)1-8CH3, –Me, –Et, –nPr, –iPr, –nBu, –iBu, –sBu, –tBu, –(CH2)4CH3, or –(CH2)5CH6. Embodiment 263. The compound of any one of embodiments 1 to 258, wherein each instance of R11is independently –CH2F, –CHF2, –CF3, –CH2CF3, –CH(CF3)2, –CF2CF3, –OH, – OMe, –OEt, –C(O)(CH2)0-18(CH3), –C(O)(CH2)1-8(C=C)(CH2)1-8CH3, –Me, or –Et. 20 Embodiment 264. The compound of any one of embodiments 1 to 258, wherein each instance of R11is independently –CH2F, –CHF2,–CF3, –OH, –Me, –C(O)(CH2)0-18(CH3), or – C(O)(CH2)1-8(C=C)(CH2)1-8CH3. Embodiment 265. The compound of any one of embodiments 1 to 264, wherein p is 0, 1, 2, or 3. 25 Embodiment 266. The compound of any one of embodiments 1 to 264, wherein p is 1, 2, or 3. Embodiment 267. The compound of any one of embodiments 1 to 264, wherein p is 1. Embodiment 268. The compound of any one of embodiments 1 to 264, wherein p is 2. Embodiment 269. The compound of any one of embodiments 1 to 264, wherein p is 3. Embodiment 270. The compound of any one of embodiments 1 to 264, wherein p is 0. Embodiment 271. The compound of any one of embodiments 1 to 270, wherein R10is 5 selected from: 10 Embodiment 272. The compound of any one of embodiments 1 to 271, wherein each instance of Raais independently H, C1-12alkyl, C2-12alkenyl, C2-12alkynyl, C1-12heteroalkyl, C6-10aryl, C3-10carbocyclyl, 5-10–membered heteroaryl having 1-6 heteroatoms independently 15 selected from nitrogen, oxygen, and sulfur, or a 3-10–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. Embodiment 273. The compound of any one of embodiments 1 to 271, wherein each instance of Raais independently H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6heteroalkyl, C6aryl, C3-8carbocyclyl, 5-8–membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-8–membered heterocyclyl having 1-4 heteroatoms 5 independently selected from nitrogen, oxygen, and sulfur. Embodiment 274. The compound of any one of embodiments 1 to 271, wherein each instance of Raais independently H, C1-20alkyl, or C2-20alkenyl. Embodiment 275. The compound of any one of embodiments 1 to 271, wherein each instance of Raais independently H or C1-6alkyl. 10 Embodiment 276. The compound of any one of embodiments 1 to 275, wherein each instance of Rbbis independently H, C1-12alkyl, C2-12alkenyl, C2-12alkynyl, C1-12heteroalkyl, C6-10aryl, C3-10carbocyclyl, 5-10–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-10–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. 15 Embodiment 277. The compound of any one of embodiments 1 to 275, wherein each instance of Rbbis independently H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6heteroalkyl, C6aryl, C3-8carbocyclyl, 5-8–membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-8–membered heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. 20 Embodiment 278. The compound of any one of embodiments 1 to 275, wherein each instance of Rbbis independently H, C1-20alkyl, or C2-20alkenyl. Embodiment 279. The compound of any one of embodiments 1 to 275, wherein each instance of Rbbis independently H or C1-6alkyl. Embodiment 280. The compound of embodiment 1, wherein the compound is a compound of 25 Formula A-I, A-II, A-III, A-IV, or A-V: Embodiment 281. The compound of embodiment 1, wherein the compound is a compound of Formula A-IVa-1, A-IVa-2, A-IVa-3, A-IVb-1, A-IVb-2, A-IVb-3, A-IVb-4, A-IVb-5, A-IVc-1, A-IVc-2, A-IVc-3, A-IVc-4, A-IVc-5, A-IVc-6, A-IVc-7, A-IVc-8, A-IVc-9, A-IVc-10, A-IVd- 1, A-IVd-2, A-IVd-3, A-IVd-4, A-IVd-5, A-IVd-6, A-IVd-7, A-IVd-8, A-IVd-9, A-IVd-10, 5 A-IVd-11, A-IVd-12, A-IVd-13, A-IVd-14, A-IVd-15, A-IVd-16, A-IVd-17, A-IVd-18, A-IVd- 19, or A-IVd-20: 1)p )p , or a pharmaceutically acceptable salt thereof. Embodiment 282. The compound of embodiment 1, wherein the compound is a compound of Formula A-Va-1, A-Va-2, A-Va-3, A-Vb-1, A-Vb-2, A-Vb-3, A-Vb-4, A-Vb-5, A-Vc-1, A-Vc- 2, A-Vc-3, A-Vc-4, A-Vc-5, A-Vc-6, A-Vc-7, A-Vc-8, A-Vc-9, A-Vc-10, A-Vd-1, A-Vd-2, 5 A-Vd-3, A-Vd-4, A-Vd-5, A-Vd-6, A-Vd-7, A-Vd-8, A-Vd-9, A-Vd-10, A-Vd-11, A-Vd-12, A-Vd-13, A-Vd-14, A-Vd-15, A-Vd-16, A-Vd-17, A-Vd-18, A-Vd-19, or A-Vd-20:

[0021]

[0022] or a pharmaceutically acceptable salt thereof. Embodiment 283. The compound of embodiment 1, wherein the compound is a compound of Formula A-Vaa: or a pharmaceutically acceptable salt thereof 5 Embodiment 284. The compound of embodiment 2, wherein the compound is a compound of Formula B-I, B-II, B-III, B-IV, or B-V:

[0023] or a pharmaceutically acceptable salt thereof. Embodiment 285. The compound of embodiment 2, wherein the compound is a compound of Formula B-IVa-1, B-IVa-2, B-IVa-3, B-IVb-1, B-IVb-2, B-IVb-3, B-IVb-4, B-IVb-5, B-IVc-1, B-IVc-2, B-IVc-3, B-IVc-4, B-IVc-5, B-IVc-6, B-IVc-7, B-IVc-8, B-IVc-9, B-IVc-10, B-IVd-1,5 B-IVd-2, B-IVd-3, B-IVd-4, B-IVd-5, B-IVd-6, B-IVd-7, B-IVd-8, B-IVd-9, B-IVd-10, B-IVd- 11, B-IVd-12, B-IVd-13, B-IVd-14, B-IVd-15, B-IVd-16, B-IVd-17, B-IVd-18, B-IVd-19, or B- IVd-20:

[0024] or a pharmaceutically acceptable salt thereof. Embodiment 286. The compound of embodiment 2, wherein the compound is a compound of Formula B-Va-1, B-Va-2, B-Va-3, B-Vb-1, B-Vb-2, B-Vb-3, B-Vb-4, B-Vb-5, B-Vc-1, B-Vc-2, B-Vc-3, B-Vc-4, B-Vc-5, B-Vc-6, B-Vc-7, B-Vc-8, B-Vc-9, B-Vc-10, B-Vd-1, B-Vd-2, B-Vd-3, B-Vd-4, B-Vd-5, B-Vd-6, B-Vd-7, B-Vd-8, B-Vd-9, B-Vd-10, B-Vd-11, B-Vd-12, B-Vd-13, B- Vd-14, B-Vd-15, B-Vd-16, B-Vd-17, B-Vd-18, B-Vd-19, or B-Vd-20:

[0025] or a pharmaceutically acceptable salt thereof. Embodiment 287. The compound of embodiment 2, wherein the compound is a compound of Formula B-Vaa: or a pharmaceutically acceptable salt thereof. 5 Embodiment 288. The compound of embodiment 3, wherein the compound is a compound of Formula C-I, C-II, C-III, C-IV, or C-V:

[0026] or a pharmaceutically acceptable salt thereof, an atropisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof. Embodiment 289. The compound of embodiment 3, wherein the compound is a compound of Formula C-IVa-1, C-IVa-2, C-IVa-3, C-IVb-1, C-IVb-2, C-IVb-3, C-IVb-4, C-IVb-5, C-IVc-1, 5 C-IVc-2, C-IVc-3, C-IVc-4, C-IVc-5, C-IVc-6, C-IVc-7, C-IVc-8, C-IVc-9, C-IVc-10, C-IVd-1, C-IVd-2, C-IVd-3, C-IVd-4, C-IVd-5, C-IVd-6, C-IVd-7, C-IVd-8, C-IVd-9, C-IVd-10, C-IVd- 11, C-IVd-12, C-IVd-13, C-IVd-14, C-IVd-15, C-IVd-16, C-IVd-17, C-IVd-18, C-IVd-19, or C- IVd-20:

[0027] , or a pharmaceutically acceptable salt thereof, an atropisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof. Embodiment 290. The compound of embodiment 3, wherein the compound is a compound of Formula C-Va-1, C-Va-2, C-Va-3, C-Vb-1, C-Vb-2, C-Vb-3, C-Vb-4, C-Vb-5, C-Vc-1, C-Vc-2, C-Vc-3, C-Vc-4, C-Vc-5, C-Vc-6, C-Vc-7, C-Vc-8, C-Vc-9, C-Vc-10, C-Vd-1, C-Vd-2, C-Vd-3, C-Vd-4, C-Vd-5, C-Vd-6, C-Vd-7, C-Vd-8, C-Vd-9, C-Vd-10, C-Vd-11, C-Vd-12, C-Vd-13, C- 5 Vd-14, C-Vd-15, C-Vd-16, C-Vd-17, C-Vd-18, C-Vd-19, or C-Vd-20: or a pharmaceutically acceptable salt thereof, an atropisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof. Embodiment 291. The compound of any one of embodiments 1 to 290, wherein the compound has a rotational energy barrier for interconversion between atropisomers of greater 5 than about 25 kcal / mol to about 40 kcal / mol. Embodiment 292. The compound of any one of embodiments 1 to 290, wherein the compound has a rotational energy barrier for interconversion between atropisomers of greater than about 28 kcal / mol. Embodiment 293. The compound of any one of embodiments 1 to 290, wherein the 10 compound has a rotational energy barrier for interconversion between atropisomers of greater than about 30 kcal / mol. Embodiment 294. The compound of any one of embodiments 1 to 290, wherein the compound has a rotational energy barrier for interconversion between atropisomers of greater than about 33 kcal / mol. Embodiment 295. The compound of any one of embodiments 1 to 290, wherein the 5 compound has a rotational energy barrier for interconversion between atropisomers of greater than about 35 kcal / mol. Embodiment 296. The compound of any one of embodiments 1 to 290, wherein the compound has a rotational energy barrier for interconversion between atropisomers of greater than about 38 kcal / mol. 10 Embodiment 297. The compound of any one of embodiments 1 to 290, wherein the compound has a rotational energy barrier for interconversion between atropisomers of greater than about 40 kcal / mol. Embodiment 298. The compound of embodiment 1 or 2, wherein the compound is a compound shown in Table 1, or a pharmaceutically acceptable salt thereof. 15 Embodiment 299. The compound of embodiment 1 or 2, wherein the compound is a compound shown in Table 2, or a pharmaceutically acceptable salt thereof. Embodiment 300. The compound of embodiment 3, wherein the compound is a compound shown in Table 2, or a pharmaceutically acceptable salt thereof, an atropisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof. 20 Embodiment 301. A pharmaceutical composition comprising a compound of any one of embodiments 1 to 300, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient thereof. Embodiment 302. A method of treating a disorder in a subject in need thereof, comprising administering to the subject an effective amount of a compound of any one of embodiments 1 to 25 300, or a pharmaceutical composition of embodiment 301. Embodiment 303. The method of embodiment 302, wherein the disorder is cancer. Embodiment 304. The method of embodiment 303, wherein the cancer is a carcinoma, a leukemia, a lymphoma, a myeloma, a sarcoma, or a solid tumor cancer. Embodiment 305. The method of embodiment 303 or 304, wherein the cancer is a bladder cancer, a breast cancer, a colon cancer, a colorectal cancer, a gastric cancer, a liver cancer, a lung cancer, an ovarian cancer, a pancreatic cancer, a prostate cancer, a renal cancer, a skin cancer, or a thyroid cancer. 5 EXAMPLES The disclosure is further illustrated by the following examples, which serve as exemplary modes of making and practicing the compounds, compositions, and methods of the disclosure. The scope of the disclosure is not to be construed as limited to specific embodiments described in these examples, which are illustrative only. 10 In the synthetic procedures described below, it is understood that reaction conditions (e.g., atmosphere, duration, solvent or solvent systems, temperature, and workup protocols) are selected from standard conditions for that reaction, unless otherwise indicated. Some of the starting materials and reagents used in the synthetic procedures described below are commercially available or are readily prepared by standard procedures from known materials. 15 Additional compounds not specifically exemplified below may be synthesized using the synthetic procedures described below (e.g., in combination with other starting materials or reagents). Abbreviations Abbreviations: acetic acid (AcOH), acetonitrile (AcCN); ammonia chloride (NH4Cl); 20 aqueous (aq); N-chlorosuccinimide (NCS); (benzotriazol-l-yloxy)tripyrrolidino- phosphonium hexafluorophosphate (PyBOP); benzyl (Bn); benzyloxycarbonyl (Cbz or CBZ); (1- [Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate or hexafluorophosphate azabenzotriazole tetramethyl uronium (HATU); [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (Pd(dppf)Cl2); N-25 bromosuccinimide (NBS); tert-butyloxycarbonyl (BOC or Boc); carbon dioxide (CO2); 1,1’- carbonyldiimidazole (CDI); N-chlorosuccinimide (NCS); cesium carbonate (Cs2CO3); deuterated chloroform (CDCl3); deuterated methanol (CD3OD); diethyl azodicarboxylate (DEAD); m-chloroperoxybenzoic acid (mCPBA); dichloromethane (DCM); dichlorotin (SnCl2); diethylamine (DEA); diethyl azodicarboxylate (DEAD); diethylaminosulfur trifluoride (DAST); 30 diisopropyl azodicarboxylate (DIAD); dimethyl sulfoxide (DMSO); N,N-diisopropylethylamine (DIPEA); 4-N,N-dimethylaminopyridine (DMAP); N,N-dimethylformamide (DMF); l-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDCI); diethyl ether (ether or Et2O); N,N- diisopropylethylamine (DIPEA); ethyl (Et); equivalent(s) (eq); ethanol (EtOH); ethyl acetate (EtOAc); formic acid (FA); gram(s) (g); hexane (Hex); hour(s) (h or hr); hydrogen (H2); hydrogen chloride (HCl); iodine (I2); iron powder (Fe); 2-propanol or isopropanol (IPA); liter(s) (L); lithium chloride (LiCl); lithium diisopropylamide (LDA); lithium hydroxide (LiOH); mass spectrum (ms or MS); mass-to-charge ratio (m / z); methanol (MeOH); methyl (Me); methyl tert- 5 butyl ether (MTBE); 4-methylbenzenesulfonic acid (TsOH); N-methylimidazole (NMI); microliter(s) (μι); milligram(s) (mg); milliliter(s) (mL); millimole (mmol); minute(s) (min); molecular sieves (MS); palladium on carbon (Pd / C); phosphorus trichloride (PCl3); potassium carbonate (K2CO3); potassium nitrate (KNO3); petroleum ether (PE); 2-propanol (IPA); retention time (tR); room temperature (rt); saturated aqueous (sat’d); saturated aq sodium chloride solution 10 (brine); selenium dioxide (SeO2); sodium hydroxide (NaOH); sodium sulfate (Na2SO4); sulfuric acid (H2SO4); supercritical fluid chromatography (SFC); tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4); tetrahydrofuran (THF); N,N,N′,N′- tetramethylchloroformamidinium hexafluorophosphate (TCFH); triethylamine (TEA); trifluoroacetic acid (TFA); trimethylsilyl (TMS); triphenylphosphine (PPh3); volume (v); and 15 water (H2O). In chemical structures disclosed herein, stereogenic centers and / or stereogenic axes can be described according to the Enhanced Stereo Representation format (MDL / Biovia, e.g. using labels “or1”, “or2”, “abs”, “and1”). General Methods 20 All chemicals were purchased from commercial sources, unless otherwise noted. Reactions were usually carried out at room temperature unless otherwise noted. Reactions sensitive to moisture or air were performed under nitrogen using anhydrous solvents and reagents. Concentration of solutions was carried out on a rotary evaporator under reduced pressure. The progress of reactions was monitored by analytical thin layer chromatography 25 (TLC), and liquid chromatograph-mass spectrometry (LCMS). TLC was performed on Liang Chen Gui Yuan TLC plates precoated with silica gel GF254, layer thickness 0.25 mm. The plates were visualized using 254 nm UV and / or by exposure to cerium ammonium molybdate (CAM) or p-anisaldehyde staining solutions followed by charring. High-performance liquid chromatography (HPLC) was performed on a Shimadzu ^ LCMS-2020 system supported by 30 LabSolutions ^ (Version 5.99 SP2) using following analysis methods: LCMS Method A: HALO ^ C18 column, 3.0 x 30 mm, 5 µm; mobile phase: Phase A: 0.0375% TFA in water (v / v), Phase B: 0.01875% TFA in AcCN (v / v); gradient elution: 5% ~9 5% of B in A over 1.05 min; flow rate 1.5 mL / min; UV wavelength 220 nm & 254 nm. LCMS Method B: HALO ^ C18 column, 3.0 x 30 mm, 5 µm; mobile phase: Phase A: 0.0375% TFA in water (v / v), Phase B: 0.01875% TFA in AcCN (v / v); gradient elution: 0% ~ 60% of B in A over 1.05 min; flow rate 1.5 mL / min; UV wavelength 220 nm & 254 nm. LCMS Method C: Kinetex ^ EVO C18 column, 30 x 2.1 mm, 5 µm; mobile phase: Phase 5 A: 0.0375% TFA in water (v / v), Phase B: 0.01875% TFA in AcCN (v / v); gradient elution: 5% ~ 95% of B in A over 1.55 min; flow rate 1.5 mL / min; UV wavelength 220 nm & 254 nm. LCMS Method D: Kinetex ^ EVO C18 column, 30 x 2.1 mm, 5 µm; mobile phase: Phase A: 0.0375% TFA in water (v / v), Phase B: 0.01875% TFA in AcCN (v / v); gradient elution: 0% ~ 60% of B in A over 1.55 min; flow rate 1.5 mL / min; UV wavelength 220 nm & 254 nm. 10 LCMS Method E: Kinetex ^ EVO C18 column, 30 x 2.1 mm, 5 µm; mobile phase: Phase A: 0.025% NH3·H2O in water (v / v), Phase B: AcCN; gradient elution: 5% ~ 95% of B in A over 1.55 min; flow rate 1.5 mL / min; UV wavelength 220 nm & 254 nm. LCMS Method F: Kinetex ^ EVO C18 column, 30 x 2.1 mm, 5 µm; mobile phase: Phase A: 0.025% NH3•H2O in water (v / v), Phase B: AcCN; gradient elution: 0% ~ 60% of B in A over 15 1.55 min; flow rate 1.5 mL / min; UV wavelength 220 nm & 254 nm. Mass analysis was performed on a Shimadzu ^ PDA Detector with electrospray ionization in positive ion detection mode and the scan range of the mass-to-charge ratio was 100- 1000. NMR analyses were acquired on either Bruker AVANCE NEO 400 (400 MHz) or ZKNJ 20 Quantum_1plus(400 MHz) in CDCl3solutions unless otherwise noted. Chemical shifts (δ)1H NMR spectra were reported in parts per million. Tetramethylsilane (TMS) was used as internal reference in CDCl3solutions, and residual CH3OH peak or TMS was used as internal reference in CD3OD solutions. Coupling constants (J) were reported in hertz (Hz). Flash chromatography was performed using either a Biotage™ Flash Chromatography 25 apparatus or a Teledyne ISCO CombiFlash®. Normal-phase chromatography was carried out on column: YMC Triart C18150 x 25 mm, 5 µm; mobile phase: [water(FA)-AcCN]; column: Welch Ultimate XB-CN 250 x 50, 10 µm; mobile phase: [Hexane-EtOH (0.1% NH3•H2O). Reverse-phase chromatography was performed on: 1) Waters ^ Xbridge 150 x 25mm, 5 µm column; mobile phase: [water( NH4HCO3)-AcCN]; 2) Phenomenex ^ Luna C18150 x 25 mm, 30 10 µm , column; mobile phase: [water(FA)-AcCN]; 3) Phenomenex ^ Luna C18150 x 25 mm, 10 µm , column; mobile phase: [water(TFA)-AcCN]; 4) Welch Xtimate C18150 x 25 mm, 5 µm , column; mobile phase: [water(HCl)-ACN]. Analysis and separation of chiral molecules were performed using supercritical fluid chromatography (SFC). SFC analysis method A: SHIMADZU ^ LC-30ADSF, Column: (S,S)Whelk-O ^ 150 x 4.6 mm I.D., 3.5 µm, Mobile phase: Phase A for CO2, and Phase B for EtOH (0.05% DEA); Gradient elution: 60% EtOH (0.05% DEA) in CO2; Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100 Bar. 5 SFC analysis method B: Column: Chiralpak ^ AD-3, 50 x 4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, and Phase B for IPA+AcCN (0.05% DEA); Gradient elution: 50% IPA + AcCN (0.05% DEA) in CO2, Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100 Ba. SFC analysis method C: Column: Chiralcel ^ OX-3, 50 x 4.6 mm I.D., 3 µm; Mobile 10 phase: Phase A for CO2, and Phase B for IPA + AcCN (0.05% DEA); Gradient elution: 50% IPA + AcCN (0.05% DEA) in CO2, Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100 Bar. SFC analysis method D: Column: Chiralpak ^ IF-3, 50 x 4.6 mm I.D., 3 µm, Mobile phase: Phase A for CO2, and Phase B for MeOH + AcCN (0.05% DEA); Gradient elution: 50% 15 MeOH + AcCN (0.05% DEA) in CO2, Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100 Bar. General Synthetic Schemes The compounds disclosed herein can be synthesized and tested according to the following schemes and examples, or modifications thereof, using readily available starting 20 materials, reagents and conventional synthesis procedures. In these reactions, it is also possible to make use of variations which are themselves known to those of ordinary skill in this art, but are not mentioned here in greater detail. Furthermore, other methods for preparing compounds disclosed herein will be readily apparent to those of ordinary skill in the art in light of the following schemes and examples. Unless otherwise indicated, all variables are as defined above. 25

[0028] Scheme 1 describes a convenient method to prepare (3-phenyl)-quinazolin-4(3H)-one compounds of general structures 1-10 in the present disclosure. An appropriately substituted phenol 1-1 can be readily alkylated with a suitable alkylating reaction partner R3–X (X = Cl, Br, I, mesylate, tosylate or triflate) in the presence of a suitable base such as potassium carbonate, 5 sodium carbonate, cesium carbonate, pyridine, lutidine, triethylamine or N,N- diisopropylethylamine in a suitable solvent such as acetonitrile, tetrahydrofuran, dioxane, N,N- dimethylformamide or N-methyl-2-pyrrolidone at or above room temperature. Treatment of ketone 1-2 with N-chlorosuccinimide provides α-chloroketone 1-3 which is subsequently reacted with an appropriately substituted nucleophilic 5-membered azaheterocycles or azaarenes such as 10 pyrrolidine, pyrrolidinone, imidazole, triazole or tetrazole or an appropriately substituted nucleophilic 6-membered azaheterocycles such as piperazine 1-4 to give compound 1-5. Reduction of nitro 1-5 to generate amine 1-6 can be achieved either using a suitable noble metal catalyst such as palladium on charcoal, platinum oxide or Raney nickel catalyst in the presence of hydrogen in a suitable solvent such as methanol, ethanol or water, or using a suitable reducing 15 reagent such as tin(II) chloride, lithium aluminum hydride or sodium borohydride in a suitable solvent such as tetrahydrofuran, diethyl ether, dioxane, dichloromethane, chloroform or dichloroethane, or using a suitable metal such as tin, iron or zinc in the presence of a suitable acid such as hydrochloric acid, acetic acid or formic acid in a suitable solvent such as methanol, ethanol, acetic acid or water. Coupling of amine 1-6 with carboxylic acid 1-8 generates 20 quinazolinone 1-9 by using a suitable reagent such as phosphorus trichloride, phosphorus oxychloride, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, hexafluorophosphate azabenzotriazole tetramethyl uranium or (benzotriazol-1- yloxy)tripyrrolidinophosphonium hexafluorophosphate in the presence of a suitable base such as potassium carbonate, sodium carbonate, cesium carbonate, pyridine, lutidine, triethylamine or25 N,N-diisopropylethylamine in a suitable solvent such as acetonitrile, tetrahydrofuran, N,N- dimethylformamide or N-methyl-2-pyrrolidone followed by warming. Acid 1-8 is synthesized by acylation of amino acid 1-7 with α-chloroacetyl chloride in the presence of a suitable base such as potassium carbonate, sodium carbonate, cesium carbonate, pyridine, lutidine, triethylamine or N,N-diisopropylethylamine in a suitable solvent such as tetrahydrofuran, N,N- 30 dimethylformamide or N-methyl-2-pyrrolidone. Treatment of chloride 1-9 with a suitable amine such as an appropriately substituted piperazine 1-10 lead to amine 1-11 in a suitable solvent such as tetrahydrofuran, N,N-dimethylformamide or N-methyl-2-pyrrolidone at or above room temperature. Acylation of amine 1-11 to give the target molecule 1-12 is achieved by treatment with an appropriate reagent such as an appropriate acyl chloride or an appropriate carboxylic acid in the presence of a suitable coupling reagent such as phosphorus trichloride, phosphorus oxychloride, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, hexafluorophosphate azabenzotriazole tetramethyl uranium or (benzotriazol-1- yloxy)tripyrrolidinophosphonium hexafluorophosphate in the presence of a suitable base such as 5 potassium carbonate, sodium carbonate, cesium carbonate, pyridine, lutidine, triethylamine or diisopropylethylamine in a suitable solvent such as dichloromethane, ethyl acetate, chloroform, tetrahydrofuran, N,N-dimethylformamide or N-methyl-2-pyrrolidone. Alternatively, treatment of chloride 1-9 with an appropriately substituted piperazine 1-13 protected by an appropriate protecting group P such as tert-butyloxycarbonyl, fluorenylmethyloxycarbonyl or 10 benzyloxycarbonyl generates 1-14 which is subsequently deprotected under appropriate conditions and followed by acylation as described above to give the target molecule 1-12. Lastly, alkylation of chloride 1-9 with an appropriately substituted amine 1-15 in the presence of a suitable base such as potassium carbonate, sodium carbonate, cesium carbonate, pyridine, lutidine, triethylamine or diisopropylethylamine in a suitable solvent such as dichloromethane, 15 ethyl acetate, chloroform, tetrahydrofuran, N,N-dimethylformamide or N-methyl-2-pyrrolidone at or above room temperature furnishes the target molecule 1-12 directly. Apparently, if the target molecule 1-12 having an appropriate protecting group such as tert-butyloxycarbonyl, fluorenylmethyloxycarbonyl or benzyloxycarbonyl on 4-, 5- or 6-membered azaheterocycles 1-4, the resulting protecting group could be deprotected under appropriate conditions to unmask the 20 reactive amino group which can be further functionalized by alkylation or acylation to give desired target molecules as described in the present disclosure.

[0029] Scheme 2 delineates an alternative method to synthesize (3-phenyl)-quinazolin-4(3H)- one compounds of general structures 2-11 in the present disclosure. α-Chlorokenone 2-1 is 5 treated with an appropriate salt of acetate such as sodium acetate or potassium acetate or with acetic acid in the presence of a suitable base potassium carbonate, sodium carbonate, cesium carbonate, pyridine, lutidine, triethylamine or diisopropylethylamine in a suitable solvent such as acetonitrile, tetrahydrofuran, N,N-dimethylformamide or N-methyl-2-pyrrolidone at elevated temperature. Conversion of nitro 2-2 to advanced intermediate 2-8 can be accomplished using 10 procedures described in Scheme 1 starting from nitro 1-5 to the final product 1-11. Deacetylation of 2-8 gives alcohol 2-9 under basic hydrolysis conditions using a suitable base such as sodium hydroxide, potassium hydroxide or sodium methoxide in a suitable solvent such as methanol, ethanol, acetonitrile, dioxane, tetrahydrofuran, dichloromethane, N,N- dimethylformamide, N-methyl-2-pyrrolidone, water or a suitable mix solvent using two or more 15 of these solvents. Conversion of the hydroxyl group in 2-9 to a bromide 2-10 is accomplished using carbon tetrabromide and triphenylphosphine in a suitable solvent such as dichloromethane at ambient temperature. Alternatively, the hydroxyl group in 2-9 can be converted into other good leaving group such as chloride, mesylate, tosylate or triflate using appropriate conditions. Finally, treatment of 2-10 with an appropriately substituted nucleophilic 4-membered 20 azaheterocycles such as azetidines, or an appropriately substituted 5-membered azaheterocycles or azaarenes such as pyrrolidine, pyrrolidinone, imidazole, triazole or tetrazole or an appropriately substituted nucleophilic 6-membered azaheterocycles such as piperazine 2-11 gives general structures 2-12 in the present disclosure. Scheme 3 outlines another method to prepare (3-phenyl)-quinazolin-4(3H)-one compounds of general structures 3-8 in the present disclosure. Treatment of an appropriately functionalized piperazine 3-1 using ethyl 2-chloroacetate in the presence of a suitable base such as potassium carbonate, sodium carbonate, cesium carbonate, pyridine, lutidine, triethylamine or 10 diisopropylethylamine in a suitable solvent such as acetonitrile, dioxane, tetrahydrofuran, dichloromethane, N,N-dimethylformamide, N-methyl-2-pyrrolidone. Ethyl ester in 3-1 is hydrolyzed to give carboxylic acid or its salt 3-2 using a suitable base such as sodium hydroxide, potassium hydroxide or sodium methoxide in a suitable solvent such as methanol, ethanol, acetonitrile, dioxane, tetrahydrofuran, dichloromethane, N,N-dimethylformamide, N-methyl-2- 15 pyrrolidone, water or a suitable mix solvent using two or more of these solvents. Coupling of carboxylic acid 3-2 with amine 3-3 leads to 3-5 by using a suitable reagent such as phosphorus trichloride, phosphorus oxychloride, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, hexafluorophosphate azabenzotriazole tetramethyl uranium or (benzotriazol-1- yloxy)tripyrrolidinophosphonium hexafluorophosphate in the presence of a suitable base such as 20 potassium carbonate, sodium carbonate, cesium carbonate, pyridine, lutidine, triethylamine or diisopropylethylamine in a suitable solvent such as dichloromethane, ethyl acetate, chloroform, tetrahydrofuran, N,N-dimethylformamide or N-methyl-2-pyrrolidone. Hydrolysis of ethyl ester in 3-5 gives carboxylic acid 3-6 by using a suitable base such as sodium hydroxide, potassium hydroxide or sodium methoxide in a suitable solvent such as methanol, ethanol, acetonitrile, dioxane, tetrahydrofuran, dichloromethane, N,N-dimethylformamide, N-methyl-2-pyrrolidone, water or a suitable mix solvent using two or more of these solvents. Condensation of carboxylic acid 3-6 and amine 3-7 to generate general structures 3-8 is accomplished using a suitable 5 reagent such as phosphorus trichloride, phosphorus oxychloride, 1-ethyl-3-(3- dimethylaminopropyl) carbodiimide hydrochloride, hexafluorophosphate azabenzotriazole tetramethyl uranium or (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate in the presence of a suitable base such as potassium carbonate, sodium carbonate, cesium carbonate, pyridine, lutidine, triethylamine or N,N-diisopropylethylamine in a suitable solvent 10 such as acetonitrile, tetrahydrofuran, N,N-dimethylformamide or N-methyl-2-pyrrolidone followed by warming. Alternatively, treatment of piperazine 3-1 using ethyl 2-chloro-2- oxoacetate followed by similar transformation steps gives corresponding amide containing (indicated by bracket) general structures 3-8.

[0030]

[0031] Finally, Scheme 4 provides another method to prepare (3-phenyl)-quinazolin-4(3H)-one compounds of general structures 4-10 in the present disclosure. Treatment of an appropriately functionalized piperazine 4-1 protected with a suitable protecting group P such as tert- butyloxycarbonyl, fluorenylmethyloxycarbonyl or benzyloxycarbonyl with ethyl 2-chloroacetate 5 gives amine 4-2 in the presence of a suitable base such as potassium carbonate, sodium carbonate, cesium carbonate, pyridine, lutidine, triethylamine or diisopropylethylamine in a suitable solvent such as acetonitrile, dioxane, tetrahydrofuran, dichloromethane, N,N- dimethylformamide, N-methyl-2-pyrrolidone at or above room temperature. Ethyl ester in 4-2 is hydrolyzed to give carboxylic acid or its salt 4-3 using a suitable base such as sodium hydroxide, 10 potassium hydroxide or sodium methoxide in a suitable solvent such as methanol, ethanol, acetonitrile, dioxane, tetrahydrofuran, dichloromethane, N,N-dimethylformamide, N-methyl-2- pyrrolidone, water or a suitable mix solvent using two or more of these solvents. Coupling of carboxylic acid 4-3 with amine 4-4 leads to 4-5 by using a suitable reagent such as phosphorus trichloride, phosphorus oxychloride, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide 15 hydrochloride, hexafluorophosphate azabenzotriazole tetramethyl uranium or (benzotriazol-1- yloxy)tripyrrolidinophosphonium hexafluorophosphate in the presence of a suitable base such as potassium carbonate, sodium carbonate, cesium carbonate, pyridine, lutidine, triethylamine or diisopropylethylamine in a suitable solvent such as dichloromethane, ethyl acetate, chloroform, tetrahydrofuran, N,N-dimethylformamide or N-methyl-2-pyrrolidone. Hydrolysis of ethyl ester 20 in 4-5 gives carboxylic acid 4-6 using a suitable base such as sodium hydroxide, potassium hydroxide or sodium methoxide in a suitable solvent such as methanol, ethanol, acetonitrile, dioxane, tetrahydrofuran, dichloromethane, N,N-dimethylformamide, N-methyl-2-pyrrolidone, water or a suitable mix solvent using two or more of these solvents. Condensation of carboxylic acid 4-6 and amine 4-7 is accomplished using a suitable reagent such as phosphorus trichloride, 25 phosphorus oxychloride, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, hexafluorophosphate azabenzotriazole tetramethyl uranium or (benzotriazol-1- yloxy)tripyrrolidinophosphonium hexafluorophosphate in the presence of a suitable base such as potassium carbonate, sodium carbonate, cesium carbonate, pyridine, lutidine, triethylamine or N,N-diisopropylethylamine in a suitable solvent such as acetonitrile, tetrahydrofuran, N,N- 30 dimethylformamide or N-methyl-2-pyrrolidone followed by warming to generate quinazolinone 4-8. Deprotection of 4-8 under appropriate conditions gives amine 4-9 which is appropriately acylated as described above to give the target molecule 4-10. Exemplary Synthetic Schemes EXAMPLE 1. Synthesis of 3-(5-(2-(1H-Imidazol-1-yl)acetyl)-2-isopropoxyphenyl)-2- ((4-(2-phenoxyacetyl)piperazin-1-yl)methyl)quinazolin-4(3H)-one 5 Step A: 1-(4-Isopropoxy-3-nitrophenyl)ethan-1-one To a solution of 1-(4-hydroxy-3-nitrophenyl)ethan-1-one (100.0 g, 552 mmol, 1.0 eq) in DMF (1.0 L) was added K2CO3(91.6 g, 662 mmol, 1.2 eq). The mixture was stirred at 20 °C for 15 min. To the resulting mixture 2-iodopropane (188.0 g, 1.10 mol, 110.40 mL, 2.0 eq) was added dropwise. After stirring at 70 °C for 16 hr, the reaction mixture was poured into water 10 (1.0 L) and extracted with EtOAc (4 x500 mL). The organic layers were combined, washed with brine (3 x 300 mL) and dried over Na2SO4. The solid was filtered off and the filtrate was concentrated. The residue was purified by silica gel chromatography (PE / EtOAc = 20 / 1 to 3 / 1, v / v) to give the title compound (100.0 g, 447.98 mmol, 81 % yield) as a light-yellow solid.1H NMR: δ 8.36 (d, J = 2.4 Hz, 1H), 8.11 (dd, J = 2.4, 8.8 Hz, 1H), 7.13 (d, J = 8.8 Hz, 1H),4.80 (td, 15 J = 6.0, 12.4 Hz, 1H), 2.59 (s, 3H), 1.43 (d, J = 6.0 Hz, 6H). Step B: 2-Chloro-1-(4-isopropoxy-3-nitrophenyl)ethan-1-one To a solution of 1-(4-isopropoxy-3-nitrophenyl)ethan-1-one (48.0 g, 215 mmol, 1.0 eq) in AcCN (750 mL) was added NCS (28.7 g, 215 mmol, 1.0 eq) and TsOH•H2O (61.4 g, 322 mmol, 1.5 eq). After stirring at 40 °C for 2 hr, the reaction mixture was concentrated and the residue 5 was purified by silica gel chromatography (PE / EtOAc = 20 / 1 to 3 / 1, v / v) to give the title compound (50.0 g, 194.0 mmol, 90 % yield) as a yellow solid.1H NMR: δ = 8.28 (d, J = 2.4 Hz, 1H), 8.05 (dd, J = 2.4, 8.8 Hz, 1H), 7.12 (d, J = 9.2 Hz, 1H), 4.76 (td, J = 6.0, 12.0 Hz, 1H), 4.60 (s, 2H), 1.36 (d, J = 6.0 Hz, 6H). 10 Step C: 2-(1H-Imidazol-1-yl)-1-(4-isopropoxy-3-nitrophenyl)ethan-1-one A solution of 2-chloro-1-(4-isopropoxy-3-nitrophenyl)ethan-1-one (50.0 g, 194.0 mmol, 1.0 eq) and imidazole (39.6 g, 582.1 mmol, 3.0 eq) in DCM (250 mL) was stirred at 40 °C for 2 hr. The reaction mixture was quenched with sat’d NaHCO3(250 mL) at 25 °C, then diluted with DCM (100 mL) and extracted with DCM (3 x 300 mL). The organic layers were combined, 15 washed with brine (2 x 250 mL) and dried over Na2SO4. The solid was filtered off and the filtrate was concentrated to give a residue, which was purified by silica gel chromatography (PE / EtOAc = 20 / 1 to 4 / 1, v / v, and then DCM / MeOH = 20 / 1 to 10 / 1, v / v) to give the title compound (43.0 g, 148.6 mmol, 77 % yield) as a yellow solid. LCMS: tR= 0.841 min, m / z = 290.1 [M+H]+.1H NMR: δ 8.34 (d, J = 2.0 Hz, 1H), 8.10 (dd, J = 2.4, 8.8 Hz, 1H), 7.47 (s, 1H), 20 7.17 (d, J = 8.8 Hz, 1H), 7.07 (s, 1H), 6.91 (s, 1H), 5.37 (s, 2H), 4.80 (td, J = 6.2, 12.4 Hz, 1H), 1.41 (d, J = 6.4 Hz, 6H). Step D: 1-(3-Amino-4-isopropoxyphenyl)-2-(1H-imidazol-1-yl)ethan-1-one To a solution of 2-(1H-imidazol-1-yl)-1-(4-isopropoxy-3-nitrophenyl)ethan-1-one (20.0 25 g, 69.14 mmol, 1.0 eq) in MeOH (250 mL) was added Pd / C (3.0 g, 10 wt.%). The suspension was degassed and purged with H2for 3 times, and then stirred under H2(15 Psi) at 20 °C for 2 hr. The catalyst was filtered off through a pad of Celite ^ and washed with MeOH (100 mL). The combined filtrate was concentrated to give the crude title compound as a yellow solid, which was used without further purification. LCMS: m / z = 260.2 [M+H]+, tR= 0.399 min.1H NMR 30 (CD3OD): δ = 7.60 (s, 1H), 7.43 - 7.35 (m, 2H), 7.03 (s, 1H), 6.99 (s, 1H), 6.90 (d, J = 8.4 Hz, 1H), 5.49 (s, 2H), 4.69 (td, J = 6.0, 12.0 Hz, 1H), 1.36 (d, J = 6.0 Hz, 6H). Step E: 2-(2-Chloroacetamido)benzoic acid To a solution of 2-aminobenzoic acid (39.8 g, 290.1 mmol, 1.0 eq) in DMF (200 mL) was added a s...

Claims

y CLAIMS What is claimed is:

1. A compound of Formula A: 5or a pharmaceutically acceptable salt thereof, wherein: each of X1, X2, X3, and X4is independently N or CR1; each of X5and X6is independently N or CR2; 10 each instance of R1is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R1a, C2-20alkenyl optionally substituted with 1-4 instances of R1a, or C2-20alkynyl optionally substituted with 1-4 instances of R1a; each instance of R1ais independently RB; each instance of R2is independently H, RA, C1-20alkyl optionally substituted with 1-4 15 instances of R2a, C2-20alkenyl optionally substituted with 1-4 instances of R2a, or C2-20alkynyl optionally substituted with 1-4 instances of R2a; each instance of R2ais independently RB; R3is C1-6alkyl, C1-6haloalkyl, C3-6carbocyclyl, or 3-6–membered heterocyclyl having 1- 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R3is optionally 20 substituted with 1-6 instances of R3a; each R3ais independently halo, –CN, –NO2, C1-6alkyl, or C1-6alkoxy; each of R4and R5is independently H, halo, –CN, –NO2, C1-6alkyl, C1-6haloalkyl, or C3-6carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3-6carbocyclylene;Ring A is C3-14carbocyclylene or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R6is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R6a, C2-20alkenyl optionally substituted with 1-4 instances of R6a, or C2-20alkynyl 5 optionally substituted with 1-4 instances of R6a; each instance of R6ais independently RB; L0is –O–, –NRL1–, –C(O)–, or –CRL2RL3–; L1is absent, –O–, –NRL1–, –C(O)–, or –CRL2RL3–; L2is absent, –O–, –NRL1–, or –CRL2RL3–; 10 each instance of RL1is independently H or C1-6alkyl; each instance of RL2and RL3is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-6carbocyclyl, or RL2and RL3are taken together with the atom to which each is attached to form C3-6carbocyclylene; R7is15 Ring B is C6-14aryl or 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R8is independently oxo, RA, C1-20 alkyl optionally substituted with 1-4 instances of R8a, C2-20alkenyl optionally substituted with 1-4 instances of R8a, or C2-20alkynyl optionally substituted with 1-4 instances of R8a; 20 each instance of R8ais independently RB; Y1is –C(O)– or –CRY1RY2–; each instance of RY1and RY2is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-6carbocyclyl, or RY1and RY2are taken together with the atom to which each is attached to form C3-6carbocyclylene; 25 Y2is absent or Ring D is C6-14arylene, C3-14carbocyclylene, 5-14–membered heteroarylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur;each instance of R9is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R9a, C2-20alkenyl optionally substituted with 1-4 instances of R9a, or C2-20alkynyl optionally substituted with 1-4 instances of R9a; each instance of R9ais independently RB; 5 Y3is absent, –C(O)–, or –CRY1RY2–; each instance of RY1and RY2is independently H or C1-6alkyl; R10is H, halo, –CN, –NO2, –OH, –NH2, C1-6haloalkyl, C1-20alkyl, C1-20heteroalkyl, C2- 20alkenyl, C2-20alkynyl, orRing E is C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 10 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R11is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R11a, C2-20alkenyl optionally substituted with 1-4 instances of R11a, or C2-20alkynyl optionally substituted with 1-4 instances of R11a; 15 each instance of R11ais independently RB; each instance of RAis independently C1-6 haloalkyl, halo, –CN, –NO2, –SF5, –C(O)Raa, – C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, – S(O)2F, –S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, or –SRaa; each instance of RBis independently halo, –CN, –NO2, –SF5, –C(O)Raa, –C(O)ORaa, –20 C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, –S(O)2F, – S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, –SRaa, or –Si(Raa)3; each instance of Raais independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-20heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl 25 having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of Rbbis independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-20heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 30 m is 0, 1, 2, 3, 4, 5, or 6; n is 0, 1, 2, 3, 4, 5, or 6; o is 0, 1, 2, 3, 4, 5, or 6; andp is 0, 1, 2, 3, 4, 5, or 6.

2. A compound of Formula B:5 or a pharmaceutically acceptable salt thereof, each of X1, X2, X3, and X4is independently N or CR1; each of X5and X6is independently N or CR2; each instance of R1is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R1a, C2-20alkenyl optionally substituted with 1-4 instances of R1a, or C2-20alkynyl 10 optionally substituted with 1-4 instances of R1a; each instance of R1ais independently RB; each instance of R2is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R2a, C2-20alkenyl optionally substituted with 1-4 instances of R2a, or C2-20alkynyl optionally substituted with 1-4 instances of R2a; 15 each instance of R2ais independently RB; R3is C1-6alkyl, C1-6haloalkyl, C3-6carbocyclyl, or 3-6–membered heterocyclyl having 1- 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R3is optionally substituted with 1-6 instances of R3a; each R3ais independently halo, –CN, –NO2, C1-6alkyl, or C1-6alkoxy; 20 each of R4and R5is independently H, halo, –CN, –NO2, C1-6alkyl, C1-6haloalkyl, or C3-6carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3-6carbocyclylene; Ring A is C3-14carbocyclylene or 3-14–membered heterocyclylene having 1-6each instance of R6is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R6a, C2-20alkenyl optionally substituted with 1-4 instances of R6a, or C2-20alkynyl optionally substituted with 1-4 instances of R6a; each instance of R6ais independently RB; 5 L0is –NRL1–, –C(O)–, or –CRL2RL3–; L1is absent, –O–, –NRL1–, –C(O)–, or –CRL2RL3–; L2is absent, –O–, –NRL1–, or –CRL2RL3–; each instance of RL1is independently H or C1-6alkyl; each instance of RL2and RL3is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-610 carbocyclyl, or RL2and RL3are taken together with the atom to which each is attached to form C3-6carbocyclylene; R7isRing B is C6-14aryl or 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 15 each instance of R8is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R8a, C2-20alkenyl optionally substituted with 1-4 instances of R8a, or C2-20alkynyl optionally substituted with 1-4 instances of R8a; each instance of R8ais independently RB; Y1is –C(O)– or –CRY1RY2–; 20 each instance of RY1and RY2is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-6carbocyclyl, or RY1and RY2are taken together with the atom to which each is attached to form C3-6carbocyclylene; Y2is absent orRing D is C6-14arylene, C3-14carbocyclylene, 5-14–membered heteroarylene having 1-6 25 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R9is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R9a, C2-20alkenyl optionally substituted with 1-4 instances of R9a, or C2-20alkynyl 30 optionally substituted with 1-4 instances of R9a;each instance of R9ais independently RB; Y3is absent, –C(O)–, or –CRY1RY2–; each instance of RY1and RY2is independently H or C1-6alkyl; R10is H, halo, –CN, –NO2, –OH, –NH2, C1-6haloalkyl, C1-20alkyl, C1-20heteroalkyl, C2- 520alkenyl, C2-20alkynyl, orRing E is C6-14 aryl, C3-14 carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R11is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 10 instances of R11a, C2-20alkenyl optionally substituted with 1-4 instances of R11a, or C2-20alkynyl optionally substituted with 1-4 instances of R11a; each instance of R11ais independently RB; each instance of RAis independently C1-6haloalkyl, halo, –CN, –NO2, –SF5, –C(O)Raa, – C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, – 15 S(O)2F, –S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, or –SRaa; each instance of RBis independently halo, –CN, –NO2, –SF5, –C(O)Raa, –C(O)ORaa, – C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, –S(O)2F, – S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, –SRaa, or –Si(Raa)3; each instance of Raais independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-2020 heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of Rbbis independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-20heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms 25 independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; m is 0, 1, 2, 3, 4, 5, or 6; n is 0, 1, 2, 3, 4, 5, or 6; o is 0, 1, 2, 3, 4, 5, or 6; and 30 p is 0, 1, 2, 3, 4, 5, or 6. 3 A compound of Formula C:or a pharmaceutically acceptable salt thereof, an atropisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof, 5 wherein: each of X1, X2, X3, and X4is independently N or CR1; each of X5and X6is independently N or CR2; each instance of R1is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R1a, C2-20alkenyl optionally substituted with 1-4 instances of R1a, or C2-20alkynyl 10 optionally substituted with 1-4 instances of R1a; each instance of R1ais independently RB; each instance of R2is independently H, RA, C1-20alkyl optionally substituted with 1-4 instances of R2a, C2-20alkenyl optionally substituted with 1-4 instances of R2a, or C2-20alkynyl optionally substituted with 1-4 instances of R2a; 15 each instance of R2ais independently RB; R3is C1-6alkyl, C1-6haloalkyl, C3-6carbocyclyl, or 3-6–membered heterocyclyl having 1- 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R3is optionally substituted with 1-6 instances of R3a; each R3ais independently halo, –CN, –NO2, C1-6alkyl, or C1-6alkoxy; 20 each of R4and R5is independently H, halo, –CN, –NO2, C1-6alkyl, C1-6haloalkyl, or C3-6carbocyclyl, or R4and R5are taken together with the atom to which each is attached to form carbonyl or C3-6carbocyclylene; Ring A is C3-14carbocyclylene or 3-14–membered heterocyclylene having 1-6each instance of R6is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R6a, C2-20alkenyl optionally substituted with 1-4 instances of R6a, or C2-20alkynyl optionally substituted with 1-4 instances of R6a; each instance of R6ais independently RB; 5 L0is –NRL1–, –C(O)–, or –CRL2RL3–; L1is absent, –O–, –NRL1–, –C(O)–, or –CRL2RL3–; L2is absent, –O–, –NRL1–, or –CRL2RL3–; each instance of RL1is independently H or C1-6alkyl; each instance of RL2and RL3is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-610 carbocyclyl, or RL2and RL3are taken together with the atom to which each is attached to form C3-6carbocyclylene; R7isRing B is C6-14aryl or 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 15 each instance of R8is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R8a, C2-20alkenyl optionally substituted with 1-4 instances of R8a, or C2-20alkynyl optionally substituted with 1-4 instances of R8a; each instance of R8ais independently RB; Y1is –C(O)– or –CRY1RY2–; 20 each instance of RY1and RY2is independently H, halo, –CN, –NO2, C1-6alkyl, or C3-6carbocyclyl, or RY1and RY2are taken together with the atom to which each is attached to form C3-6carbocyclylene; Y2is absent orRing D is C6-14arylene, C3-14carbocyclylene, 5-14–membered heteroarylene having 1-6 25 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R9is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 instances of R9a, C2-20alkenyl optionally substituted with 1-4 instances of R9a, or C2-20alkynyleach instance of R9ais independently RB; Y3is absent, –C(O)–, or –CRY1RY2–; each instance of RY1and RY2is independently H or C1-6alkyl; R10is H, halo, –CN, –NO2, –OH, –NH2, C1-6haloalkyl, C1-20alkyl, C1-20heteroalkyl, C2- 520alkenyl, C2-20alkynyl, orRing E is C6-14 aryl, C3-14 carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R11is independently oxo, RA, C1-20alkyl optionally substituted with 1-4 10 instances of R11a, C2-20alkenyl optionally substituted with 1-4 instances of R11a, or C2-20alkynyl optionally substituted with 1-4 instances of R11a; each instance of R11ais independently RB; each instance of RAis independently C1-6haloalkyl, halo, –CN, –NO2, –SF5, –C(O)Raa, – C(O)ORaa, –C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, – 15 S(O)2F, –S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, or –SRaa; each instance of RBis independently halo, –CN, –NO2, –SF5, –C(O)Raa, –C(O)ORaa, – C(O)N(Rbb)2, –C(O)NRbbORbb, –C(O)SRaa, –S(O)Raa, –S(O)ORaa, –S(O)N(Rbb)2, –S(O)2F, – S(O)2Raa, –S(O)2ORaa, –S(O)2N(Rbb)2, –N(Rbb)2, –ORaa, –SRaa, or –Si(Raa)3; each instance of Raais independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-2020 heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of Rbbis independently H, C1-20alkyl, C2-20alkenyl, C2-20alkynyl, C1-20heteroalkyl, C6-14aryl, C3-14carbocyclyl, 5-14–membered heteroaryl having 1-6 heteroatoms 25 independently selected from nitrogen, oxygen, and sulfur, or a 3-14–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; m is 0, 1, 2, 3, 4, 5, or 6; n is 0, 1, 2, 3, 4, 5, or 6; o is 0, 1, 2, 3, 4, 5, or 6; and 30 p is 0, 1, 2, 3, 4, 5, or 6, provided that wheneach of X5and X6is CH; R3iseach of R4and R5is H; Ring A is5 L0–C(O)–; L1is –CH2–; L2is –O–; R7isR8is halo; 10 Y1is –CRY1RY2–; Y2is absent or; and Y3is absent or –CRY1RY2–, then R10is other than H, halo,15 4. The compound of any one of claims 1 to 3, wherein X1is N.

5. The compound of any one of claims 1 to 3, wherein X2is N.

6. The compound of any one of claims 1 to 3, wherein X3is N.

7. The compound of any one of claims 1 to 3, wherein X4is N.

8. The compound of any one of claims 1 to 3, wherein X1is CR1, X2is CR1, X3is CR1, and 20 X4is CR1.

9. The compound of any one of claims 1 to 8, wherein each instance of R1is independently R1is independently H, RA, or C2-20alkynyl optionally substituted with 1-4 instances of R1a.

10. The compound of any one of claims 1 to 9, wherein X5is CR2and X6is CR2.

11. The compound of any one of claims 1 to 10, wherein each instance of R2is independently 5 H, RA, C1-6alkyl optionally substituted with 1-4 instances of R2a, C2-6alkenyl optionally substituted with 1-4 instances of R2a, or C2-6alkynyl optionally substituted with 1-4 instances of R2a.

12. The compound of any one of claims 1 to 11, wherein R3is C1-6alkyl, C1-6haloalkyl, C3-6carbocyclyl, or 3-6–membered heterocyclyl having 1-2 heteroatoms independently selected from 10 nitrogen, oxygen, and sulfur.

13. The compound of any one of claims 1 to 11, wherein R3is –Me, –Et, –nPr, –iPr, –nBu, – iBu, –sBu, –tBu, –(CH2)4CH3, –(CH2)5CH6, –CH2F, –CHF2, –CF3, –CH2CF3, –CH(CF3)2, – CF2CF3, –CH(CF3)(CF2OCH3), cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or15 14. The compound of any one of claims 1 to 11, wherein R3is –iPr or –CH2CF3.

15. The compound of any one of claims 1 to 14, wherein R4is H, –F, –Cl, , –CN, –NO2, – OH, –Me, –Et, –iPr, –tBu, –CF3, –OMe, –OEt, –OiPr, –OtBu, or R4and R5are takentogether with the atom to which each is attached to form carbonyl or cyclopropylene ring.

16. The compound of any one of claims 1 to 15, wherein R5is H, –F, –Cl, , –CN, –NO2, – 20 OH, –Me, –Et, –iPr, –tBu, –CF3, –OMe, –OEt, –OiPr, –OtBu or R4and R5are takentogether with the atom to which each is attached to form carbonyl or cyclopropylene ring.

17. The compound of any one of claims 1 to 16, wherein Ring A is C3-10carbocyclylene or 3-10–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

18. The compound of any one of claims 1 to 16, wherein Ring A is 3-10–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

19. The compound any one of claims 1 to 16, wherein Ring A together with its R65 substituents is selected from 120. The compound of any one of claims 1 to 19, wherein each instance of R6is independently oxo RAor C1 20alkyl optionally substituted with 14 instances of R6a21. The compound of any one of claims 1 to 19, wherein each instance of R6is independently oxo, C1-6haloalkyl, halo, –CN, –NO2, –C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or C1-20alkyl optionally substituted with 1-4 instances of R6a.

22. The compound of any one of claims 1 to 21, wherein m is 0, 1, 2, or 3. 5 23. The compound any one of claims 1 to 22, wherein Ring A together with its R6substituents is selected from:

24. The compound of any one of claims 1 to 23, wherein L1is –NRL1– or –CRL2RL3–. 10 25. The compound of any one of claims 1 to 24, wherein L2is –O– or –CRL2RL3–.

26. The compound of any one of claims 1 to 25, wherein each instance of RL1is independently H, –Me, –Et, –nPr, –iPr, –nBu, –iBu, –sBu, –tBu, –(CH2)4CH3, –(CH2)5CH6.

27. The compound of any one of claims 1 to 26, wherein RL2is H, –F, –Cl, –Br, –Me, –Et, – nPr, –iPr, –nBu, –iBu, –sBu, –tBu, –(CH2)4CH3, –(CH2)5CH6, cyclopropyl, cyclobutyl, 15 cyclopentyl, or cyclohexyl, or RL2and RL3are taken together to form cyclopropylene, cyclobutylene, cyclopentylene, or cyclohexylene.

28. The compound of any one of claims 1 to 27, wherein RL3is H, –F, –Cl, –Br, –Me, –Et, – nPr, –iPr, –nBu, –iBu, –sBu, –tBu, –(CH2)4CH3, –(CH2)5CH6, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, or RL2and RL3are taken together to form cyclopropylene, 20 cyclobutylene, cyclopentylene, or cyclohexylene.

29. The compound of any one of claims 1 to 28, wherein L0is –NH–, –C(O)–, or –CH2–.

30. The compound of any one of claims 1 to 28, wherein L0is –C(O)–.

31. The compound of any one of claims 1 to 30, wherein L1is absent, or L1is –NH–, – NCH3–, –CH2–, or –CH(CH3)–.

32. The compound of any one of claims 1 to 30, wherein L2is absent, or L2is –O– or – CRL2RL3–. 5 33. The compound of any one of claims 1 to 32, wherein Ring B is C6-14aryl.

34. The compound of any one of claims 1 to 32, wherein Ring B is 5-14–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

35. The compound of any one of claims 1 to 32, wherein R7is selected from: 1036. The compound of any one of claims 1 to 32, wherein R7is selected from: 1537. The compound of any one of claims 1 to 36, wherein each instance of R8is independently oxo, C1-6haloalkyl, halo, –CN, –NO2, –C(O)Raa, –N(Rbb)2, –ORaa, –SRaa, or C1-20alkyl optionally substituted with 1-4 instances of R8a.

38. The compound of any one of claims 1 to 37, wherein n is 0, 1, 2, or 3. 20 39. The compound of any one of claims 1 to 38, wherein R7is selected from:

40. The compound of any one of claims 1 to 39, wherein Y1is –C(O)–.

41. The compound of any one of claims 1 to 39, wherein Y1is –CRY1RY2–. 5 42. The compound of any one of claims 1 to 41, wherein Y3is absent.

43. The compound of any one of claims 1 to 41, wherein Y3is –CRY1RY2–.

44. The compound of any one of claims 1 to 43, wherein RY1is H, –F, –Cl, –Br, –Me, –Et, – nPr, –iPr, –nBu, –iBu, –sBu, –tBu, –(CH2)4CH3, –(CH2)5CH6, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, or RY1and RY2are taken together with the atom to which each is 10 attached to form carbonyl, cyclopropylene, cyclobutylene, cyclopentylene, or cyclohexylene.

45. The compound of any one of claims 1 to 44, wherein RY2is H, –F, –Cl, –Br, –Me, –Et, – nPr, –iPr, –nBu, –iBu, –sBu, –tBu, –(CH2)4CH3, –(CH2)5CH6, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, or RY1and RY2are taken together with the atom to which each is attached to form carbonyl, cyclopropylene, cyclobutylene, cyclopentylene, or cyclohexylene. 15 46. The compound of any one of claims 1 to 45, wherein Y1is –C(O)–, –CH2–, or – CH(CH3)–.

47. The compound of any one of claims 1 to 46, wherein Y3is absent, –CH2–, or – CH(CH3)–.

48. The compound of any one of claims 1 to 47, wherein Y2is absent. 20 49. The compound of any one of claims 1 to 48, wherein Y2is50. The compound of any one of claims 1 to 49, wherein Ring D is C6-10arylene, C3-10carbocyclylene, 5-10–membered heteroarylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-10–membered heterocyclylene having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. 5 51. The compound of any one of claims 1 to 49, wherein Ring D together with its R9substituents is52. The compound of any one of claims 1 to 51, wherein R10is H, halo, –CN, –NO2, –OH, – NH2, C1-6haloalkyl, C1-20alkyl, C1-20heteroalkyl, C2-20alkenyl, or C2-20alkynyl.

53. The compound of any one of claims 1 to 51, wherein R10is10 54. The compound of any one of claims 1 to 51, wherein Ring E is C6-10aryl, C3-10carbocyclyl, 5-10–membered heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 3-10–membered heterocyclyl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

55. The compound of any one of claims 1 to 51, wherein R10is selected from:

56. The compound of any one of claims 1 to 55, wherein each instance of R11is independently oxo, RA, C1-20alkyl optionally substituted with 1-2 instances of R11a, C2-20alkenyl 5 optionally substituted with 1-2 instances of R11a, or C2-20 alkynyl optionally substituted with 1-2 instances of R11a.

57. The compound of any one of claims 1 to 56, wherein p is 0, 1, 2, or 3.

58. The compound of any one of claims 1 to 57, wherein R10is selected from: 1059. The compound of claim 1, wherein the compound is a compound of Formula A-I, A-II, A-III, A-IV, or A-V, or a pharmaceutically acceptable salt thereof. 5 60. The compound of claim 1, wherein the compound is a compound of Formula A-IVa-1, A-IVa-2, A-IVa-3, A-IVb-1, A-IVb-2, A-IVb-3, A-IVb-4, A-IVb-5, A-IVc-1, A-IVc-2, A-IVc-3, A-IVc-4, A-IVc-5, A-IVc-6, A-IVc-7, A-IVc-8, A-IVc-9, A-IVc-10, A-IVd-1, A-IVd-2, A-IVd- 3, A-IVd-4, A-IVd-5, A-IVd-6, A-IVd-7, A-IVd-8, A-IVd-9, A-IVd-10, A-IVd-11, A-IVd-12, A-IVd-13, A-IVd-14, A-IVd-15, A-IVd-16, A-IVd-17, A-IVd-18, A-IVd-19, or A-IVd-20, or a 10 pharmaceutically acceptable salt thereof .

61. The compound of claim 1, wherein the compound is a compound of Formula A-Va-1, A-Va-2, A-Va-3, A-Vb-1, A-Vb-2, A-Vb-3, A-Vb-4, A-Vb-5, A-Vc-1, A-Vc-2, A-Vc-3, A-Vc- 4, A-Vc-5, A-Vc-6, A-Vc-7, A-Vc-8, A-Vc-9, A-Vc-10, A-Vd-1, A-Vd-2, A-Vd-3, A-Vd-4, A-Vd-5, A-Vd-6, A-Vd-7, A-Vd-8, A-Vd-9, A-Vd-10, A-Vd-11, A-Vd-12, A-Vd-13, A-Vd-14, 15 A-Vd-15, A-Vd-16, A-Vd-17, A-Vd-18, A-Vd-19, or A-Vd-20, or a pharmaceutically acceptable salt thereof.

62. The compound of claim 1, wherein the compound is a compound of Formula A-Vaa. or a pharmaceutically acceptable salt thereof.

63. The compound of claim 2, wherein the compound is a compound of Formula B-I, B-II, 20 B-III, B-IV, or B-V, or a pharmaceutically acceptable salt thereof.

64. The compound of claim 2, wherein the compound is a compound of Formula B-IVa-1, B- IVa-2, B-IVa-3, B-IVb-1, B-IVb-2, B-IVb-3, B-IVb-4, B-IVb-5, B-IVc-1, B-IVc-2, B-IVc-3, B- IVc-4, B-IVc-5, B-IVc-6, B-IVc-7, B-IVc-8, B-IVc-9, B-IVc-10, B-IVd-1, B-IVd-2, B-IVd-3, B-IVd-4, B-IVd-5, B-IVd-6, B-IVd-7, B-IVd-8, B-IVd-9, B-IVd-10, B-IVd-11, B-IVd-12, B- 25 IVd-13, B-IVd-14, B-IVd-15, B-IVd-16, B-IVd-17, B-IVd-18, B-IVd-19, or B-IVd-20, or a pharmaceutically acceptable salt thereof.

65. The compound of claim 2, wherein the compound is a compound of Formula B-Va-1, B- Va-2, B-Va-3, B-Vb-1, B-Vb-2, B-Vb-3, B-Vb-4, B-Vb-5, B-Vc-1, B-Vc-2, B-Vc-3, B-Vc-4, B- Vc-5, B-Vc-6, B-Vc-7, B-Vc-8, B-Vc-9, B-Vc-10, B-Vd-1, B-Vd-2, B-Vd-3, B-Vd-4, B-Vd-5, B-Vd-6, B-Vd-7, B-Vd-8, B-Vd-9, B-Vd-10, B-Vd-11, B-Vd-12, B-Vd-13, B-Vd-14, B-Vd-15, 5 B-Vd-16, B-Vd-17, B-Vd-18, B-Vd-19, or B-Vd-20, or a pharmaceutically acceptable salt thereof.

66. The compound of claim 2, wherein the compound is a compound of Formula B-Vaa, or a pharmaceutically acceptable salt thereof.

67. The compound of claim 3, wherein the compound is a compound of Formula C-I, C-II, 10 C-III, C-IV, or C-V, or a pharmaceutically acceptable salt thereof, an atropisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.

68. The compound of claim 3, wherein the compound is a compound of Formula C-IVa-1, C- IVa-2, C-IVa-3, C-IVb-1, C-IVb-2, C-IVb-3, C-IVb-4, C-IVb-5, C-IVc-1, C-IVc-2, C-IVc-3, C- IVc-4, C-IVc-5, C-IVc-6, C-IVc-7, C-IVc-8, C-IVc-9, C-IVc-10, C-IVd-1, C-IVd-2, C-IVd-3,15 C-IVd-4, C-IVd-5, C-IVd-6, C-IVd-7, C-IVd-8, C-IVd-9, C-IVd-10, C-IVd-11, C-IVd-12, C- IVd-13, C-IVd-14, C-IVd-15, C-IVd-16, C-IVd-17, C-IVd-18, C-IVd-19, or C-IVd-20, or a pharmaceutically acceptable salt thereof, an atropisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.

69. The compound of claim 3, wherein the compound is a compound of Formula C-Va-1, C-20 Va-2, C-Va-3, C-Vb-1, C-Vb-2, C-Vb-3, C-Vb-4, C-Vb-5, C-Vc-1, C-Vc-2, C-Vc-3, C-Vc-4, C- Vc-5, C-Vc-6, C-Vc-7, C-Vc-8, C-Vc-9, C-Vc-10, C-Vd-1, C-Vd-2, C-Vd-3, C-Vd-4, C-Vd-5, C-Vd-6, C-Vd-7, C-Vd-8, C-Vd-9, C-Vd-10, C-Vd-11, C-Vd-12, C-Vd-13, C-Vd-14, C-Vd-15, C-Vd-16, C-Vd-17, C-Vd-18, C-Vd-19, or C-Vd-20, or a pharmaceutically acceptable salt thereof, an atropisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof. 25 70. The compound of claim 1 or 2, wherein the compound is a compound shown in Table 1, or a pharmaceutically acceptable salt thereof.

71. The compound of claim 1 or 2, wherein the compound is a compound shown in Table 2, or a pharmaceutically acceptable salt thereof.

72. The compound of claim 3, wherein the compound is a compound shown in Table 2, or a pharmaceutically acceptable salt thereof, an atropisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.

73. A pharmaceutical composition comprising a compound of any one of claims 1 to 72, or a 5 pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient thereof.

74. A method of treating a disorder in a subject in need thereof, comprising administering to the subject an effective amount of a compound of any one of claims 1 to 72, or a pharmaceutical composition of claim 73.

75. The method of claim 74, wherein the disorder is cancer. 10 76. The method of claim 75, wherein the cancer is a carcinoma, a leukemia, a lymphoma, a myeloma, a sarcoma, or a solid tumor cancer.

77. The method of claim 75 or 76, wherein the cancer is a bladder cancer, a breast cancer, a colon cancer, a colorectal cancer, a gastric cancer, a liver cancer, a lung cancer, an ovarian cancer, a pancreatic cancer, a prostate cancer, a renal cancer, a skin cancer, or a thyroid cancer.

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