ZHANG TINGHU (US)
KWIATKOWSKI NICHOLAS (US)
FAN MENGYANG (US)
CHE JIANWEI (US)
LU WENCHAO (US)
GRAY NATHANAEL S (US)
ZHANG TINGHU (US)
KWIATKOWSKI NICHOLAS PAUL (US)
FAN MENGYANG (US)
CHE JIANWEI (US)
LU WENCHAO (US)
WO2019040380A1 | 2019-02-28 | |||
WO2019113236A1 | 2019-06-13 | |||
WO2020092638A1 | 2020-05-07 | |||
WO2010079443A1 | 2010-07-15 | |||
WO2020002950A1 | 2020-01-02 | |||
WO2018204532A1 | 2018-11-08 | |||
WO2020243423A1 | 2020-12-03 |
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"GenBank", Database accession no. NM_001256659.2
CLAIMS What is claimed is: 1. A compound described herein is of Formula (I’’): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein: Ring A is an optionally substituted 5- or 6-membered optionally substituted heteroaryl, or optionally substituted heterocyclyl comprising at least one nitrogen atom, or a bicyclic heteroaryl; Ring B is an optionally substituted bicyclic or monocyclic aryl, or an optionally substituted carbocyclic ring; R1 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –ORa, –N(Rb)2, – SRa, –C(=O)Ra, –C(=O)ORa, –C(=O)SRa, –C(=O)N(Rb)2, –OC(=O)Ra, –OC(=O)ORa, – OC(=O)SRa, –OC(=O)N(Rb)2, –N(Rb)C(=O)Ra, –N(Rb)C(=O)ORa, –N(Rb)C(=O)SRa, – N(Rb)C(=O)N(Rb)2, –SC(=O)Ra, –SC(=O)ORa, –SC(=O)SRa, –SC(=O)N(Rb)2, –C(=NRb)Rb, –C(=NRb)ORa, –C(=NRb)SRa, –C(=NRb)N(Rb)2, –OC(=NRb)Rb, –OC(=NRb)ORa, – OC(=NRb)SRa, –OC(=NRb)N(Rb)2, –N(Rb)C(=NRb)Rb , –N(Rb)C(=NRb)ORa, – N(Rb)C(=NRb)SRa, –N(Rb) C(=NRb)N(Rb)2, –SC(=NRb)Rb, –SC(=NRb)ORa, –SC(=NRb)SRa, –SC(=NRb)N(Rb)2, –C(=S)Ra, –C(=S)ORa, –C(=S)SRa, –C(=S)N(Rb)2, –S(=O)Ra, –SO2Ra, – NRbSO2Ra, –SO2N(Rb)2, –CN, –SCN, or –NO2; X1 is –C(Rc)2O–, –OC(Rc)2–, –O–, –N(Rc)–, –S–, –C(=O)–, –C(=O)O–, – C(=O)N(Rc)–, –OC(=O)–, or –N(Rc)C(=O)–; X2 is a bond, –C(Rc)2–; –CO–, –OC(Rc)2–, –O–, –N(Rc)–, –S–, –C(=O)–, –C(=O)O–, –C(=O)N(Rc)–, –OC(=O)–, or –N(Rc)C(=O)–; V1 is =N– or =C(Rd)–; each occurrence of Ra is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; each occurrence of Rb or Rc is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group, or two instances of Rb, when present, can be joined together with the heteroatom to which they are attached to form an optionally substituted heterocyclic ring; each occurrence of Rd is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; n is 0, 1, 2, or 3; and D1 is a warhead of any one of Formulae (i-1) to (i-43): (i-11) (i-12) (i-13) (i-14) (i-15) (i-41) (i-42) (i-43) wherein: L3 is a bond or an optionally substituted C1–4 hydrocarbon chain, optionally wherein one or more carbon units of the hydrocarbon chain are independently replaced with –O–, –S–, –NRL3a–, –NRL3aC(=O)–, –C(=O)NRL3a–, –SC(=O)–, –C(=O)S–, –OC(=O)–, –C(=O)O–, –NRL3aC(=S)–, –C(=S)NRL3a–, trans–CRL3b=CRL3b–, cis–CRL3b=CRL3b–, –C≡C–, –S(=O)–, –S(=O)O–, –OS(=O)–, –S(=O)NRL3a–, –NRL3aS(=O)–, –S(=O)2–, –S(=O)2O–, –OS(=O)2–, –S(=O)2NRL3a–, or –NRL3aS(=O)2–, wherein RL3a is hydrogen, substituted or unsubstituted C1-6 alkyl, or a nitrogen protecting group, and wherein each occurrence of RL3b is independently selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two RL3b groups are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; L4 is a bond or an optionally substituted C1-4 hydrocarbon chain; RE1 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH2ORE1a, –CH2N(RE1a)2, –CH2SRE1a, –ORE1a, –N(RE1a)2, –Si(RE1a)3, and –SRE1a, wherein each occurrence of RE1a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two RE1a groups are joined to form an optionally substituted heterocyclic ring; RE2 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH2ORE2a, –CH2N(RE2a)2, –CH2SRE2a, –ORE2a, –N(RE2a)2, and –SRE2a, wherein each occurrence of RE2a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two RE2a groups are joined to form an optionally substituted heterocyclic ring; RE3 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH2ORE3a, –CH2N(RE3a)2, –CH2SRE3a, –ORE3a, –N(RE3a)2, and –SRE3a, wherein each occurrence of RE3a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two RE3a groups are joined to form an optionally substituted heterocyclic ring; or RE1 and RE3, or RE2 and RE3, or RE1 and RE2 are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; RE4 is a leaving group; RE5 is halogen; Y is –O–, –S–, or –NRE6, wherein RE6 is hydrogen, substituted or unsubstituted C1-6 alkyl, or a nitrogen protecting group; a is 1 or 2; and each instance of z is independently 0, 1, 2, 3, 4, 5, or 6. 2. The compound of claim 1, wherein X2 is –C(Rc)2–. 3. The compound of claim 1, wherein X2 is –C(H)2–. 4. The compound of claim 1, wherein X2 is a bond. 5. The compound of claim 1 or 4, of Formula (I): , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein: Ring A is an optionally substituted 5- or 6- membered heteroaryl comprising at least one nitrogen atom; Ring B is an optionally substituted bicyclic or monocyclic aryl, or an optionally substituted carbocyclic ring; R1 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –ORa, –N(Rb)2, – SRa, –C(=O)Ra, –C(=O)ORa, –C(=O)SRa, –C(=O)N(Rb)2, –OC(=O)Ra, –OC(=O)ORa, – OC(=O)SRa, –OC(=O)N(Rb)2, –N(Rb)C(=O)Ra, –N(Rb)C(=O)ORa, –N(Rb)C(=O)SRa, – N(Rb)C(=O)N(Rb)2, –SC(=O)Ra, –SC(=O)ORa, –SC(=O)SRa, –SC(=O)N(Rb)2, –C(=NRb)Rb, –C(=NRb)ORa, –C(=NRb)SRa, –C(=NRb)N(Rb)2, –OC(=NRb)Rb, –OC(=NRb)ORa, – OC(=NRb)SRa, –OC(=NRb)N(Rb)2, –N(Rb)C(=NRb)Rb , –N(Rb)C(=NRb)ORa, – N(Rb)C(=NRb)SRa, –N(Rb) C(=NRb)N(Rb)2, –SC(=NRb)Rb, –SC(=NRb)ORa, –SC(=NRb)SRa, –SC(=NRb)N(Rb)2, –C(=S)Ra, –C(=S)ORa, –C(=S)SRa, –C(=S)N(Rb)2, –S(=O)Ra, –SO2Ra, – NRbSO2Ra, –SO2N(Rb)2, –CN, –SCN, or –NO2; X1 is –C(Rc)2O–, –OC(Rc)2–, –O–, –N(Rc)–, –S–, –C(=O)–, –C(=O)O–, – C(=O)N(Rc)–, –OC(=O)–, or –N(Rc)C(=O)–; V1 is =N–, or =C(Rd)–; each occurrence of Ra is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; each occurrence of Rb or Rc is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group, or two instances of Rb, when present, can be joined together with the heteroatom to which they are attached to form an optionally substituted heterocyclic ring; each occurrence of Rd is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; n is 0, 1, 2, or 3; and D1 is a warhead of any one of Formulae (i-1) to (i-43): (i-41) (i-42) (i-43) wherein: L3 is a bond or an optionally substituted C1–4 hydrocarbon chain, optionally wherein one or more carbon units of the hydrocarbon chain are independently replaced with –O–, –S–, –NRL3a–, –NRL3aC(=O)–, –C(=O)NRL3a–, –SC(=O)–, –C(=O)S–, –OC(=O)–, –C(=O)O–, –NRL3aC(=S)–, –C(=S)NRL3a–, trans–CRL3b=CRL3b–, cis–CRL3b=CRL3b–, –C≡C–, –S(=O)–, –S(=O)O–, –OS(=O)–, –S(=O)NRL3a–, –NRL3aS(=O)–, –S(=O)2–, –S(=O)2O–, –OS(=O)2–, –S(=O)2NRL3a–, or –NRL3aS(=O)2–, wherein RL3a is hydrogen, substituted or unsubstituted C1-6 alkyl, or a nitrogen protecting group, and wherein each occurrence of RL3b is independently selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two RL3b groups are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; L4 is a bond or an optionally substituted C1-4 hydrocarbon chain; RE1 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH2ORE1a, –CH2N(RE1a)2, –CH2SRE1a, –ORE1a, –N(RE1a)2, –Si(RE1a)3, and –SRE1a, wherein each occurrence of RE1a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two RE1a groups are joined to form an optionally substituted heterocyclic ring; RE2 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH2ORE2a, –CH2N(RE2a)2, –CH2SRE2a, –ORE2a, –N(RE2a)2, and –SRE2a, wherein each occurrence of RE2a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two RE2a groups are joined to form an optionally substituted heterocyclic ring; RE3 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH2ORE3a, –CH2N(RE3a)2, –CH2SRE3a, –ORE3a, –N(RE3a)2, and –SRE3a, wherein each occurrence of RE3a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two RE3a groups are joined to form an optionally substituted heterocyclic ring; or RE1 and RE3, or RE2 and RE3, or RE1 and RE2 are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; RE4 is a leaving group; RE5 is halogen; Y is –O–, –S–, or –NRE6, wherein RE6 is hydrogen, substituted or unsubstituted C1-6 alkyl, or a nitrogen protecting group; a is 1 or 2; and each instance of z is independently 0, 1, 2, 3, 4, 5, or 6. 6. The compound of claim 1, 4, or 5, of the Formula (I-a): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. 7. The compound of any one of claims 1, or 4-6, of the Formula (I-b): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. 8. The compound of any one of claims 1, or 4-7, of the Formula (I-c): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. 9. The compound of any one of claims 1, or 4-8, of the Formula (I-d): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. 10. A compound of Formula (I’): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein: Ring A is an optionally substituted 5- or 6-membered heteroaryl comprising at least one nitrogen atom, or a bicyclic heteroaryl; Ring B is an optionally substituted bicyclic or monocyclic aryl, or an optionally substituted carbocyclic ring; R1 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –ORa, –N(Rb)2, –SRa, –C(=O)Ra, –C(=O)ORa, –C(=O)SRa, –C(=O)N(Rb)2, –OC(=O)Ra, –OC(=O)ORa, –OC(=O)SRa, –OC(=O)N(Rb)2, –N(Rb)C(=O)Ra, –N(Rb)C(=O)ORa, –N(Rb)C(=O)SRa, –N(Rb)C(=O)N(Rb)2, –SC(=O)Ra, –SC(=O)ORa, –SC(=O)SRa, –SC(=O)N(Rb)2, – C(=NRb)Rb, –C(=NRb)ORa, –C(=NRb)SRa, –C(=NRb)N(Rb)2, –OC(=NRb)Rb, – OC(=NRb)ORa, –OC(=NRb)SRa, –OC(=NRb)N(Rb)2, –N(Rb)C(=NRb)Rb , – N(Rb)C(=NRb)ORa, –N(Rb)C(=NRb)SRa, –N(Rb) C(=NRb)N(Rb)2, –SC(=NRb)Rb, – SC(=NRb)ORa, –SC(=NRb)SRa, –SC(=NRb)N(Rb)2, –C(=S)Ra, –C(=S)ORa, –C(=S)SRa, – C(=S)N(Rb)2, –S(=O)Ra, –SO2Ra, –NRbSO2Ra, –SO2N(Rb)2, –CN, –SCN, or –NO2; X1 is –C(Rc)2O–, –OC(Rc)2–, –O–, –N(Rc)–, –S–, –C(=O)–, –C(=O)O–, – C(=O)N(Rc)–, –OC(=O)–, or –N(Rc)C(=O)–; V1 is =N– or =C(Rd)–; each occurrence of Ra is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; each occurrence of Rb or Rc is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group, or two instances of Rb, when present, can be joined together with the heteroatom to which they are attached to form an optionally substituted heterocyclic ring; each occurrence of Rd is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; n is 0, 1, 2, or 3; and D1 is a warhead of any one of Formulae (i-1) to (i-43): (i-41) (i-42) (i-43) wherein: L3 is a bond or an optionally substituted C1–4 hydrocarbon chain, optionally wherein one or more carbon units of the hydrocarbon chain are independently replaced with –O–, –S–, –NRL3a–, –NRL3aC(=O)–, –C(=O)NRL3a–, –SC(=O)–, –C(=O)S–, –OC(=O)–, –C(=O)O–, –NRL3aC(=S)–, –C(=S)NRL3a–, trans–CRL3b=CRL3b–, cis–CRL3b=CRL3b–, –C≡C–, –S(=O)–, –S(=O)O–, –OS(=O)–, –S(=O)NRL3a–, –NRL3aS(=O)–, –S(=O)2–, –S(=O)2O–, –OS(=O)2–, –S(=O)2NRL3a–, or –NRL3aS(=O)2–, wherein RL3a is hydrogen, substituted or unsubstituted C1-6 alkyl, or a nitrogen protecting group, and wherein each occurrence of RL3b is independently selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two RL3b groups are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; L4 is a bond or an optionally substituted C1-4 hydrocarbon chain; RE1 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH2ORE1a, –CH2N(RE1a)2, –CH2SRE1a, –ORE1a, –N(RE1a)2, –Si(RE1a)3, and –SRE1a, wherein each occurrence of RE1a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two RE1a groups are joined to form an optionally substituted heterocyclic ring; RE2 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH2ORE2a, –CH2N(RE2a)2, –CH2SRE2a, –ORE2a, –N(RE2a)2, and –SRE2a, wherein each occurrence of RE2a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two RE2a groups are joined to form an optionally substituted heterocyclic ring; RE3 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH2ORE3a, –CH2N(RE3a)2, –CH2SRE3a, –ORE3a, –N(RE3a)2, and –SRE3a, wherein each occurrence of RE3a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two RE3a groups are joined to form an optionally substituted heterocyclic ring; or RE1 and RE3, or RE2 and RE3, or RE1 and RE2 are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; RE4 is a leaving group; RE5 is halogen; Y is –O–, –S–, or –NRE6, wherein RE6 is hydrogen, substituted or unsubstituted C1-6 alkyl, or a nitrogen protecting group; a is 1 or 2; and each instance of z is independently 0, 1, 2, 3, 4, 5, or 6. 11. The compound of claim 10, of Formula (I’-a): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. 12. The compound of claim 10 or 11, of Formula (I’-b): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. 13. The compound of any one of claims 10-12, of the Formula (I-c): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. 14. The compound of any one of claims 10-13, of the Formula (I’-d): , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. 15. The compound of any one of claims 1-14, wherein V1 is =N–. 16. The compound of any one of claims 1-14, wherein V1 is =C(Rd)–. 17. The compound of any one of claims 1-14, or 16, wherein V1 is =C(H)–. 18. The compound of any one of claims 1, 4-14, or 16-17, of the Formula (I-e): , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. 19. The compound of any one of claims 1, 4-14, or 16-18, of the Formula (I-f): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. 20. The compound of any one of claims 1, 4-14, or 16-19, of the Formula (I-g): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. 21. The compound of any one of claims 1, 4-14, or 16-20, of the Formula (I-h): , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. 22. The compound of any one of claims 1-21, wherein Ring A is optionally substituted pyrrole, optionally substituted furan, optionally substituted thiophene, optionally substituted imidazole, optionally substituted pyrazole, optionally substituted oxazole, optionally substituted isoxazole, optionally substituted thiazole, optionally substituted isothiazole, optionally substituted triazole, optionally substituted oxadiazole, optionally substituted thiadiazole, optionally substituted tetrazolyl, optionally substituted pyridine, optionally substituted pyridazine, optionally substituted pyrimidine, or optionally substituted pyrazine. 23. The compound of any one of claims 1-22, wherein Ring A is of the formula: wherein each instance of Re is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –ORg, –N(Rg)2, –SRg, –C(=O)Rg, –C(=O)ORg, –C(=O)SRg, –C(=O)N(Rg)2, –OC(=O)Rg, –OC(=O)ORg, –OC(=O)SRg, –OC(=O)N(Rg)2, –N(Rg)C(=O)Rg, –N(Rg)C(=O)ORg, –N(Rg)C(=O)SRg, –N(Rg)C(=O)N(Rg)2, –SC(=O)Rg, –SC(=O)ORg, –SC(=O)SRg, –SC(=O)N(Rg)2, –C(=NRg)Rg, –C(=NRg)ORg, –C(=NRg)SRg, – C(=NRg)N(Rg)2, –OC(=NRg)Rg, –OC(=NRg)ORg, –OC(=NRg)SRg, –OC(=NRg)N(Rg)2, – N(Rg)C(=NRg)Rg , –N(Rg)C(=NRg)ORg, –N(Rg)C(=NRg)SRg, –N(Rg) C(=NRg)N(Rg)2, – SC(=NRg)Rg, –SC(=NRg)ORg, –SC(=NRg)SRg, –SC(=NRg)N(Rg)2, –C(=S)Rg, –C(=S)ORg, – C(=S)SRg, –C(=S)N(Rg)2, –S(=O)Rg, –SO2Rg, –NRgSO2Rg, –SO2N(Rg)2, –CN, –SCN, or – NO2; each occurrence of Rf or Rg is independently D1, hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; and p is 0, 1, 2, 3, or 4. 24. The compound of any one of claims 1-23, wherein Ring A is of the formula: 25. The compound of any one of claims 1-24, wherein Ring A is of the formula: 26. The compound of any one of claims 1-23, wherein Ring A is of the formula: 27. The compound of any one of claims 1-23, or 26, wherein Ring A is of the formula: 28. The compound of any one of claims 1-23, wherein Ring A is of the formula: 29. The compound of any one of claims 1-23, or 28, wherein Ring A is of the formula: . 30. The compound of any one of claims 1-23, wherein Ring A is of the formula: . 31. The compound of any one of claims 1-23, or 30, wherein Ring A is of the formula: . 32. The compound of any one of claims 1-23, wherein Ring A is of the formula: . 33. The compound of any one of claims 1-23, or 32, wherein Ring A is of the Formula: . 34. The compound of any one of claims 1-23, wherein Ring A is of the Formula: . 35. The compound of any one of claims 1-23, or 34, wherein Ring A is of the Formula: . 36. The compound of any one of claims 1-23, wherein Ring A is of the Formula: . 37. The compound of any one of claims 1-23, or 36, wherein Ring A is of the Formula: . 38. The compound of any one of claims 1-23, wherein Ring A is of the Formula: . 39. The compound of any one of claims 1-23, or 38, wherein Ring A is of the Formula: . 40. The compound of any one of claims 1-23, wherein Ring A is of the formula: . 41. The compound of any one of claims 1-23, or 40, wherein Ring A is of the formula: . 42. The compound of any one of claims 1-23, wherein Ring A is of the formula: . 43. The compound of any one of claims 1-23, or 42, wherein Ring A is of the formula: . 44. The compound of any one of claims 1-23, or 42, wherein Ring A is of the formula: . 45. The compound of any one of claims 1-23, wherein Ring A is of the formula: . 46. The compound of any one of claims 1-23, or 45, wherein Ring A is of the Formula: . 47. The compound of any one of claims 1-23, or 45, wherein Ring A is of the Formula: . 48. The compound of any one of claims 1-23, or 45, wherein Ring A is of the Formula: . 49. The compound of any one of claims 1-23, or 45, wherein Ring A is of the Formula: . 50. The compound of any one of claims 1-23, wherein Ring A is of the Formula: . 51. The compound of any one of claims 1-23, wherein Ring A is of the Formula: . 52. The compound of any one of claims 1-23, or 51, wherein Ring A is of the Formula: . 53. The compound of any one of claims 1-23, wherein Ring A is of the Formula: . 54. The compound of any one of claims 1-23, or 53, wherein Ring A is of the Formula: . 55. The compound of any one of claims 1-23, wherein Ring A is of the Formula: . 56. The compound of any one of claims 1-23, or 55, wherein Ring A is of the Formula: . 57. The compound of any one of claims 1-23, or 55, wherein Ring A is of the Formula: . 58. The compound of any one of claims 1-23, or 55, wherein Ring A is of the Formula: . 59. The compound of any one of claims 1-23, or 55, wherein Ring A is of the Formula: . 60. The compound of any one of claims 1-23, or 55, wherein Ring A is of the Formula: . 61. The compound of any one of claims 1-23, or 55, wherein Ring A is of the Formula: . 62. The compound of any one of claims 1-23, or 55, wherein Ring A is of the Formula: . 63. The compound of any one of claims 1-23, or 55, wherein Ring A is of the Formula: . 64. The compound of any one of claims 1-23, or 55, wherein Ring A is of the Formula: . 65. The compound of any one of claims 1-23, wherein Ring A is of the Formula: . 66. The compound of any one of claims 1-23, or 65, wherein Ring A is of the Formula: . 67. The compound of any one of claims 1-23, wherein Ring A is of the Formula: . 68. The compound of any one of claims 1-23, or 67, wherein Ring A is of the Formula: . 69. The compound of any one of claims 1-23, wherein Ring A is of the Formula: . 70. The compound of any one of claims 1-23, or 69, wherein Ring A is of the Formula: . 71. The compound of any one of claims 1-23, wherein Ring A is of the Formula: . 72. The compound of any one of claims 1-23, or 71, wherein Ring A is of the Formula: . 73. The compound of any one of claims 1-23, wherein Ring A is of the Formula: . 74. The compound of any one of claims 1-23, or 73, wherein Ring A is of the Formula: . 75. The compound of any one of claims 1-23, wherein Ring A is of the Formula: . 76. The compound of any one of claims 1-23, or 75, wherein Ring A is of the Formula: . 77. The compound of any one of claims 1-23, wherein Ring A is of the Formula: . 78. The compound of any one of claims 1-23, or 77, wherein Ring A is of the Formula: . 79. The compound of any one of claims 1-23, wherein Ring A is of the Formula: . 80. The compound of any one of claims 1-23, or 79, wherein Ring A is of the Formula: . 81. The compound of any one of claims 1-80, wherein X1 is –N(Rc)–. 82. The compound of any one of claims 1-81, wherein X1 is –N(H)–. 83. The compound of any one of claims 1-82, wherein R1 is hydrogen. 84. A compound of Formula (II’): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein: Ring A is an optionally substituted 5- or 6- membered heteroaryl comprising at least one nitrogen atom, or a bicyclic heteroaryl; Ring B is an optionally substituted bicyclic or monocyclic aryl, or an optionally substituted carbocyclic ring; R2 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –ORa, –N(Rb)2, –SRa, –C(=O)Ra, –C(=O)ORa, –C(=O)SRa, –C(=O)N(Rb)2, –OC(=O)Ra, –OC(=O)ORa, –OC(=O)SRa, –OC(=O)N(Rb)2, –N(Rb)C(=O)Ra, –N(Rb)C(=O)ORa, –N(Rb)C(=O)SRa, –N(Rb)C(=O)N(Rb)2, –SC(=O)Ra, –SC(=O)ORa, –SC(=O)SRa, –SC(=O)N(Rb)2, –C(=NRb)Rb, –C(=NRb)ORa, –C(=NRb)SRa, –C(=NRb)N(Rb)2, –OC(=NRb)Rb, –OC(=NRb)ORa, –OC(=NRb)SRa, –OC(=NRb)N(Rb)2, –N(Rb)C(=NRb)Rb , – N(Rb)C(=NRb)ORa, –N(Rb)C(=NRb)SRa, –N(Rb) C(=NRb)N(Rb)2, –SC(=NRb)Rb, –SC(=NRb)ORa, –SC(=NRb)SRa, –SC(=NRb)N(Rb)2, –C(=S)Ra, –C(=S)ORa, –C(=S)SRa, –C(=S)N(Rb)2, –S(=O)Ra, –SO2Ra, –NRbSO2Ra, –SO2N(Rb)2, –CN, –SCN, or –NO2; X2 is a bond, –C(Rc)2–; –CO–, –OC(Rc)2–, –O–, –N(Rc)–, –S–, –C(=O)–, –C(=O)O–, –C(=O)N(Rc)–, –OC(=O)–, or –N(Rc)C(=O)–; each occurrence of Ra is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; each occurrence of Rb or Rc is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group, or two instances of Rb, when present, can be joined together with the heteroatom to which they are attached to form an optionally substituted heterocyclic ring; m is 0, 1, 2, 3, or 4; and D1 is a warhead of any one of Formulae (i-1) to (i-43): (i-41) (i-42) (i-43) wherein: L3 is a bond or an optionally substituted C1–4 hydrocarbon chain, optionally wherein one or more carbon units of the hydrocarbon chain are independently replaced with –O–, –S–, –NRL3a–, –NRL3aC(=O)–, –C(=O)NRL3a–, –SC(=O)–, –C(=O)S–, –OC(=O)–, –C(=O)O–, –NRL3aC(=S)–, –C(=S)NRL3a–, trans–CRL3b=CRL3b–, cis–CRL3b=CRL3b–, –C≡C–, –S(=O)–, –S(=O)O–, –OS(=O)–, –S(=O)NRL3a–, –NRL3aS(=O)–, –S(=O)2–, –S(=O)2O–, –OS(=O)2–, –S(=O)2NRL3a–, or –NRL3aS(=O)2–, wherein RL3a is hydrogen, substituted or unsubstituted C1-6 alkyl, or a nitrogen protecting group, and wherein each occurrence of RL3b is independently selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two RL3b groups are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; L4 is a bond or an optionally substituted C1-4 hydrocarbon chain; RE1 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH2ORE1a, –CH2N(RE1a)2, –CH2SRE1a, –ORE1a, –N(RE1a)2, –Si(RE1a)3, and –SRE1a, wherein each occurrence of RE1a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two RE1a groups are joined to form an optionally substituted heterocyclic ring; RE2 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH2ORE2a, –CH2N(RE2a)2, –CH2SRE2a, –ORE2a, –N(RE2a)2, and –SRE2a, wherein each occurrence of RE2a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two RE2a groups are joined to form an optionally substituted heterocyclic ring; RE3 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH2ORE3a, –CH2N(RE3a)2, –CH2SRE3a, –ORE3a, –N(RE3a)2, and –SRE3a, wherein each occurrence of RE3a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two RE3a groups are joined to form an optionally substituted heterocyclic ring; or RE1 and RE3, or RE2 and RE3, or RE1 and RE2 are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; RE4 is a leaving group; RE5 is halogen; Y is –O–, –S–, or –NRE6, wherein RE6 is hydrogen, substituted or unsubstituted C1-6 alkyl, or a nitrogen protecting group; a is 1 or 2; and each instance of z is independently 0, 1, 2, 3, 4, 5, or 6. 85. The compound of claim 84, of the Formula (II’-a): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. 86. The compound of claim 84, or 85, of the Formula (II’-b): , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. 87. The compound of any one of claims 84-86, wherein Ring A is a pyrrole, furan, thiophene, imidazole, pyrazole, oxazole, isoxazole, thiazole, isothiazole, triazole, oxadiazole, thiadiazole, tetrazolyl, pyridine, pyridazine, pyrimidine, or pyrazine. 88. The compound of any one of claims 84-87, wherein Ring A is of the Formula: , wherein each instance of Re is independently D1, hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –ORg, –N(Rg)2, –SRg, –C(=O)Rg, –C(=O)ORg, –C(=O)SRg, –C(=O)N(Rg)2, –OC(=O)Rg, –OC(=O)ORg, –OC(=O)SRg, –OC(=O)N(Rg)2, –N(Rg)C(=O)Rg, –N(Rg)C(=O)ORg, –N(Rg)C(=O)SRg, –N(Rg)C(=O)N(Rg)2, –SC(=O)Rg, –SC(=O)ORg, –SC(=O)SRg, –SC(=O)N(Rg)2, –C(=NRg)Rg, –C(=NRg)ORg, –C(=NRg)SRg, –C(=NRg)N(Rg)2, –OC(=NRg)Rg, –OC(=NRg)ORg, –OC(=NRg)SRg, –OC(=NRg)N(Rg)2, –N(Rg)C(=NRg)Rg , –N(Rg)C(=NRg)ORg, –N(Rg)C(=NRg)SRg, –N(Rg) C(=NRg)N(Rg)2, –SC(=NRg)Rg, –SC(=NRg)ORg, –SC(=NRg)SRg, –SC(=NRg)N(Rg)2, –C(=S)Rg, –C(=S)ORg, –C(=S)SRg, –C(=S)N(Rg)2, –S(=O)Rg, –SO2Rg, –NRgSO2Rg, –SO2N(Rg)2, –CN, –SCN, or –NO2; each occurrence of Rf or Rg is independently D1, hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; and p is 0, 1, 2, 3, or 4. 89. The compound of any one of claims 84-88, wherein Ring A is of the formula: . 90. The compound of any one of claims 84-88, wherein Ring A is of the formula: . 91. The compound of any one of claims 84-88, or 90, wherein Ring A is of the formula: . 92. The compound of any one of claims 84-88, or 90-91, wherein Ring A is of the formula: . 93. The compound of any one of claims 84-88, wherein Ring A is of the formula: . 94. The compound of any one of claims 84-88, or 93, wherein Ring A is of the formula: . 95. The compound of any one of claims 84-88, or 93-94, wherein Ring A is of the formula: . 96. The compound of any one of claims 84-88, wherein Ring A is of the formula: . 97. The compound of any one of claims 84-88, or 96, wherein Ring A is of the formula: . 98. The compound of any one of claims 84-88, wherein Ring A is of the formula: . 99. The compound of any one of claims 84-88, or 98, wherein Ring A is of the formula: . 100. The compound of any one of claims 84-88, or 98-99, wherein Ring A is of the formula: . 101. The compound of any one of claims 84-88, wherein Ring A is of the formula: . 102. The compound of any one of claims 84-88, wherein Ring A is of the formula: . 103. The compound of any one of claims 84-88, wherein Ring A is of the formula: . 104. The compound of any one of claims 84-103, wherein X2 is –N(Rc)–. 105. The compound of any one of claims 84-104, wherein X2 is –N(H)–. 106. The compound of any one of claims 84-105, wherein R2 is hydrogen. 107. The compound of any one of claims 1-106, wherein Ring B is an optionally substituted bicyclic or monocyclic aryl. 108. The compound of any one of claims 1-107, wherein Ring B is an optionally substituted phenyl. 109. The compound of any one of claims 1-108, wherein Ring B is of the formula: , wherein each instance of Rh is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –ORi, –N(Ri)2, –SRi, –C(=O)Ri, –C(=O)ORi, –C(=O)SRi, – C(=O)N(Ri)2, –OC(=O)Ri, –OC(=O)ORi, –OC(=O)SRi, –OC(=O)N(Ri)2, –N(Ri)C(=O)Ri, – N(Ri)C(=O)ORi, –N(Ri)C(=O)SRi, –N(Ri)C(=O)N(Ri)2, –SC(=O)Ri, –SC(=O)ORi, – SC(=O)SRi, –SC(=O)N(Ri)2, –C(=NRi)Ri, –C(=NRi)ORi, –C(=NRi)SRi, –C(=NRi)N(Ri)2, – OC(=NRi)Ri, –OC(=NRi)ORi, –OC(=NRi)SRi, –OC(=NRi)N(Ri)2, –N(Ri)C(=NRi)Ri, – N(Ri)C(=NRi)ORi, –N(Ri)C(=NRi)SRi, –N(Ri) C(=NRi)N(Ri)2, –SC(=NRi)Ri, – SC(=NRi)ORi, –SC(=NRi)SRi, –SC(=NRi)N(Ri)2, –C(=S)Ri, –C(=S)ORi, –C(=S)SRi, – C(=S)N(Ri)2, –S(=O)Ri, –SO2Ri, –NRiSO2Ri, –SO2N(Ri)2, –CN, –SCN, or –NO2; each occurrence of Ri is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; and r is 0, 1, 2, 3, 4, 5, 6, 7, or 8. 110. The compound of any one of claims 1-109, wherein Ring B is of the formula: . 111. The compound of any one of claims 1-109, wherein Ring B is of the formula: 112. The compound of any one of claims 1-106, wherein Ring B is an optionally substituted carbocyclic ring. 113. The compound of any one of claims 1-106, or 112, wherein Ring B is an optionally substituted cyclohexyl ring. 114. The compound of any one of claims 1-106, or 112-113, wherein Ring B is of the formula: , wherein each instance of Rh is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –ORi, –N(Ri)2, –SRi, –C(=O)Ri, –C(=O)ORi, –C(=O)SRi, –C(=O)N(Ri)2, –OC(=O)Ri, –OC(=O)ORi, –OC(=O)SRi, –OC(=O)N(Ri)2, –N(Ri)C(=O)Ri, –N(Ri)C(=O)ORi, –N(Ri)C(=O)SRi, –N(Ri)C(=O)N(Ri)2, –SC(=O)Ri, –SC(=O)ORi, –SC(=O)SRi, –SC(=O)N(Ri)2, –C(=NRi)Ri, –C(=NRi)ORi, –C(=NRi)SRi, –C(=NRi)N(Ri)2, –OC(=NRi)Ri, –OC(=NRi)ORi, –OC(=NRi)SRi, –OC(=NRi)N(Ri)2, –N(Ri)C(=NRi)Ri, –N(Ri)C(=NRi)ORi, –N(Ri)C(=NRi)SRi, –N(Ri) C(=NRi)N(Ri)2, –SC(=NRi)Ri, –SC(=NRi)ORi, –SC(=NRi)SRi, –SC(=NRi)N(Ri)2, –C(=S)Ri, –C(=S)ORi, –C(=S)SRi, –C(=S)N(Ri)2, –S(=O)Ri, –SO2Ri, –NRiSO2Ri, –SO2N(Ri)2, –CN, –SCN, or –NO2; each occurrence of Ri is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; and r is 0, 1, 2, 3, 4, 5, 6, 7, or 8. 115. The compound of any one of claims 1-106, or 112-114, wherein Ring B is of the formula: . 116. The compound of any one of claims 1-115, wherein D1 is 117. The compound of any one of claims 1-116, wherein D1 is 118. The compound of any one of claims 1-117, wherein D1 is 119. The compound of any one of claims 1-118, wherein D1 is 120. The compound of any one of claims 1-119, wherein D1 is 121. A compound of the formula: or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, or mixture thereof. 122. A compound of the formula: or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, or mixture thereof. 123. A compound of the formula: or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, or mixture thereof. 124. A pharmaceutical composition comprising a compound of any one of claims 1 to 123, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, or mixture thereof, and optionally a pharmaceutically acceptable excipient. 125. The pharmaceutical composition of claim 124, wherein the pharmaceutical composition comprises a therapeutically effective amount of the compound for treating a proliferative disease in a subject in need thereof. 126. A method of treating a proliferative disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 to 123, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, or mixture thereof, or a pharmaceutical composition of claim 124 or 125. 127. The method of claim 126, wherein the proliferative disease is cancer. 128. The method of claim 127, wherein the cancer is a sarcoma. 129. The method of claim 128, wherein the sarcoma is Kaposi’s sarcoma. 130. The method of claim 127, wherein the cancer is lung cancer. 131. The method of claim 130, wherein the lung cancer is a thyroid cancer. 132. The method of claim 127, wherein the cancer is breast cancer. 133. The method of claim 127, wherein the cancer is liver cancer. 134. The method of claim 127, wherein the cancer is prostate cancer. 135. The method of claim 127, wherein the cancer is pancreatic cancer. 136. The method of claim 127, wherein the cancer is colorectal cancer. 137. The method of claim 127, wherein the cancer is ovarian cancer. 138. The method of claim 127, wherein the cancer is skin cancer. 139. The method of claim 127, wherein the cancer is esophageal cancer. 140. The method of claim 127, wherein the cancer is carcinoma. 141. The method of claim 127, wherein the cancer is fallopian tube carcinoma. 142. A method of inhibiting a transcription factor in a subject in need thereof, the method comprising: administering to the subject a therapeutically effective amount of a compound of any one of claims 1 to 123, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, or mixture thereof, or a pharmaceutical composition of claim 124 or 125. 143. The method of claim 142, wherein the transcription factor is TEAD1, TEAD2, TEAD3, or TEAD4. 144. The method of any one of claims 126 to 143 further comprising administering to the subject a therapeutically effective amount of an additional pharmaceutical agent in combination with the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, or mixture thereof, or the pharmaceutical composition. 145. A method of inhibiting a transcription factor in a biological sample, the method comprising: contacting the cell or biological sample with an effective amount of a compound of any one of claims 1 to 123, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, or mixture thereof, or a pharmaceutical composition of claim 124 or 125. 146. The method of claim 145, wherein the transcription factor is TEAD1, TEAD2, TEAD3, or TEAD4. 147. The method of claim 145 or 146, further comprising contacting the biological sample with an additional pharmaceutical agent in combination with the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, or mixture thereof, or the pharmaceutical composition. 148. The method of any one of claims 145 to 147, wherein the biological sample is a cell or tissue. 149. The method of claim 144 or 147, wherein the additional pharmaceutical agent is an anti-proliferative agent. 150. Use of a compound of any one of claims 1 to 123, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, or mixture thereof, or a pharmaceutical composition of claim 124 or 125, for treating a proliferative disease in a subject in need thereof. 151. A compound of any one of claims 1 to 123, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, or mixture thereof, or a pharmaceutical composition of claim 124 or 125, for use in treating a proliferative disease in a subject in need thereof. 152. A kit comprising: a compound of any one of claims 1 to 123, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, or mixture thereof, or a pharmaceutical composition of claim 124 or 125; and instructions for administering to a subject or contacting a biological sample with the compound, or the pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, or mixture thereof, or the pharmaceutical composition. |
(i-41) (i-42) (i-43) wherein: L 3 is a bond or an optionally substituted C 1–4 hydrocarbon chain, optionally wherein one or more carbon units of the hydrocarbon chain are independently replaced with –O–, –S–, –NR L3a –, –NR L3a C(=O)–, –C(=O)NR L3a –, –SC(=O)–, –C(=O)S–, –OC(=O)–, –C(=O)O–, –NR L3a C(=S)–, –C(=S)NR L3a –, trans–CR L3b =CR L3b –, cis–CR L3b =CR L3b –, –C≡C–, –S(=O)–, –S(=O)O–, –OS(=O)–, –S(=O)NR L3a –, –NR L3a S(=O)–, –S(=O) 2 –, –S(=O) 2 O–, –OS(=O) 2 –, –S(=O) 2 NR L3a –, or –NR L3a S(=O) 2 –, wherein R L3a is hydrogen, substituted or unsubstituted C 1-6 alkyl, or a nitrogen protecting group, and wherein each occurrence of R L3b is independently selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R L3b groups are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; L 4 is a bond or an optionally substituted C 1-4 hydrocarbon chain; R E1 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH 2 OR E1a , –CH 2 N(R E1a ) 2 , –CH 2 SR E1a , –OR E1a , –N(R E1a ) 2 , –Si(R E1a )3, and –SR E1a , wherein each occurrence of R E1a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R E1a groups are joined to form an optionally substituted heterocyclic ring; R E2 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH 2 OR E2a , –CH 2 N(R E2a ) 2 , –CH 2 SR E2a , –OR E2a , –N(R E2a ) 2 , and –SR E2a , wherein each occurrence of R E2a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R E2a groups are joined to form an optionally substituted heterocyclic ring; R E3 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH 2 OR E3a , –CH 2 N(R E3a ) 2 , –CH 2 SR E3a , –OR E3a , –N(R E3a ) 2 , and –SR E3a , wherein each occurrence of R E3a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R E3a groups are joined to form an optionally substituted heterocyclic ring; or R E1 and R E3 , or R E2 and R E3 , or R E1 and R E2 are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; R E4 is a leaving group; R E5 is halogen; Y is –O–, –S–, or –NR E6 , wherein R E6 is hydrogen, substituted or unsubstituted C 1-6 alkyl, or a nitrogen protecting group; a is 1 or 2; and each instance of z is independently 0, 1, 2, 3, 4, 5, or 6. [0090] In certain embodiments, the compound of Formula (I’) is of the Formula (I’-a): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [0091] In certain embodiments, the compound of Formula (I’) is of the Formula (I’-b): , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [0092] In certain embodiments, the compound of Formula (I) is of the Formula (I-c): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [0093] In certain embodiments, the compound of Formula (I’) is of the Formula (I’-d): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [0094] In certain embodiments, a compound described herein is of Formula (I’’): , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein: Ring A is an optionally substituted 5- or 6-membered optionally substituted heteroaryl, or optionally substituted heterocyclyl comprising at least one nitrogen atom, or a bicyclic heteroaryl; Ring B is an optionally substituted bicyclic or monocyclic aryl, or an optionally substituted carbocyclic ring; R 1 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –OR a , –N(R b ) 2 , –SR a , –C(=O)R a , –C(=O)OR a , –C(=O)SR a , –C(=O)N(R b ) 2 , –OC(=O)R a , –OC(=O)OR a , –OC(=O)SR a , –OC(=O)N(R b ) 2 , –N(R b )C(=O)R a , –N(R b )C(=O)OR a , –N(R b )C(=O)SR a , –N(R b )C(=O)N(R b ) 2 , –SC(=O)R a , –SC(=O)OR a , –SC(=O)SR a , –SC(=O)N(R b ) 2 , – C(=NR b )R b , –C(=NR b )OR a , –C(=NR b )SR a , –C(=NR b )N(R b ) 2 , –OC(=NR b )R b , – OC(=NR b )OR a , –OC(=NR b )SR a , –OC(=NR b )N(R b ) 2 , –N(R b )C(=NR b )R b , – N(R b )C(=NR b )OR a , –N(R b )C(=NR b )SR a , –N(R b ) C(=NR b )N(R b ) 2 , –SC(=NR b )R b , – SC(=NR b )OR a , –SC(=NR b )SR a , –SC(=NR b )N(R b ) 2 , –C(=S)R a , –C(=S)OR a , –C(=S)SR a , – C(=S)N(R b ) 2 , –S(=O)R a , –SO 2 R a , –NR b SO 2 R a , –SO 2 N(R b ) 2 , –CN, –SCN, or –NO 2 ; X 1 is –C(R c ) 2 O–, –OC(R c ) 2 –, –O–, –N(R c )–, –S–, –C(=O)–, –C(=O)O–, –C(=O)N(R c )–, –OC(=O)–, or –N(R c )C(=O)–; X 2 is a bond, –C(R c ) 2 –; –CO–, –OC(R c ) 2 –, –O–, –N(R c )–, –S–, –C(=O)–, –C(=O)O–, –C(=O)N(R c )–, –OC(=O)–, or –N(R c )C(=O)–; V 1 is =N– or =C(R d )–; each occurrence of R a is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; each occurrence of R b or R c is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group, or two instances of R b , when present, can be joined together with the heteroatom to which they are attached to form an optionally substituted heterocyclic ring; each occurrence of R d is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; n is 0, 1, 2, or 3; and D 1 is a warhead of any one of Formulae (i-1) to (i-43):
(i-41) (i-42) (i-43) wherein: L 3 is a bond or an optionally substituted C 1–4 hydrocarbon chain, optionally wherein one or more carbon units of the hydrocarbon chain are independently replaced with –O–, –S–, –NR L3a –, –NR L3a C(=O)–, –C(=O)NR L3a –, –SC(=O)–, –C(=O)S–, –OC(=O)–, –C(=O)O–, –NR L3a C(=S)–, –C(=S)NR L3a –, trans–CR L3b =CR L3b –, cis–CR L3b =CR L3b –, –C≡C–, –S(=O)–, –S(=O)O–, –OS(=O)–, –S(=O)NR L3a –, –NR L3a S(=O)–, –S(=O) 2 –, –S(=O) 2 O–, –OS(=O) 2 –, –S(=O) 2 NR L3a –, or –NR L3a S(=O) 2 –, wherein R L3a is hydrogen, substituted or unsubstituted C 1-6 alkyl, or a nitrogen protecting group, and wherein each occurrence of R L3b is independently selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R L3b groups are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; L 4 is a bond or an optionally substituted C 1-4 hydrocarbon chain; R E1 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH 2 OR E1a , –CH 2 N(R E1a ) 2 , –CH 2 SR E1a , –OR E1a , –N(R E1a ) 2 , –Si(R E1a )3, and –SR E1a , wherein each occurrence of R E1a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R E1a groups are joined to form an optionally substituted heterocyclic ring; R E2 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH 2 OR E2a , –CH 2 N(R E2a ) 2 , –CH 2 SR E2a , –OR E2a , –N(R E2a ) 2 , and –SR E2a , wherein each occurrence of R E2a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R E2a groups are joined to form an optionally substituted heterocyclic ring; R E3 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH 2 OR E3a , –CH 2 N(R E3a ) 2 , –CH 2 SR E3a , –OR E3a , –N(R E3a ) 2 , and –SR E3a , wherein each occurrence of R E3a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R E3a groups are joined to form an optionally substituted heterocyclic ring; or R E1 and R E3 , or R E2 and R E3 , or R E1 and R E2 are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; R E4 is a leaving group; R E5 is halogen; Y is –O–, –S–, or –NR E6 , wherein R E6 is hydrogen, substituted or unsubstituted C 1-6 alkyl, or a nitrogen protecting group; a is 1 or 2; and each instance of z is independently 0, 1, 2, 3, 4, 5, or 6. [0095] In certain embodiments, X 2 is a bond. In certain embodiments, X 2 is –CH 2 O–. In certain embodiments, X 2 is –OCH 2 –. In certain embodiments, X 2 is –O–, –N(R c )–, –S–, –C(=O), –C(=O)O–, –C(=O)N(R c )–, –OC(=O)–, or –N(R c )C(=O)–. In certain embodiments, X 2 is –O–. In certain embodiments, X 2 is –S–. In certain embodiments, X 2 is –C(=O)–. In certain embodiments, X 2 is –C(=O)O–. In certain embodiments, X 2 is –C(=O)N(R c )–. In certain embodiments, X 2 is –OC(=O)–. In certain embodiments, X 2 is –N(R c )C(=O)–. In certain embodiments, X 2 is –N(R c )–. In certain embodiments, X 2 is –N(H)–. In certain embodiments, X is –N(Me)–. [0096] In certain embodiments, a compound of Formula (I’’) is described herein as a compound of Formula (I’-1): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein: Ring A is an optionally substituted 5- or 6-membered heteroaryl comprising at least one nitrogen atom, or a bicyclic heteroaryl; Ring B is an optionally substituted bicyclic or monocyclic aryl, or an optionally substituted carbocyclic ring; R 1 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –OR a , –N(R b ) 2 , –SR a , –C(=O)R a , –C(=O)OR a , –C(=O)SR a , –C(=O)N(R b ) 2 , –OC(=O)R a , –OC(=O)OR a , –OC(=O)SR a , –OC(=O)N(R b ) 2 , –N(R b )C(=O)R a , –N(R b )C(=O)OR a , –N(R b )C(=O)SR a , –N(R b )C(=O)N(R b ) 2 , –SC(=O)R a , –SC(=O)OR a , –SC(=O)SR a , –SC(=O)N(R b ) 2 , – C(=NR b )R b , –C(=NR b )OR a , –C(=NR b )SR a , –C(=NR b )N(R b ) 2 , –OC(=NR b )R b , – OC(=NR b )OR a , –OC(=NR b )SR a , –OC(=NR b )N(R b ) 2 , –N(R b )C(=NR b )R b , – N(R b )C(=NR b )OR a , –N(R b )C(=NR b )SR a , –N(R b ) C(=NR b )N(R b ) 2 , –SC(=NR b )R b , – SC(=NR b )OR a , –SC(=NR b )SR a , –SC(=NR b )N(R b ) 2 , –C(=S)R a , –C(=S)OR a , –C(=S)SR a , – C(=S)N(R b ) 2 , –S(=O)R a , –SO 2 R a , –NR b SO 2 R a , –SO 2 N(R b ) 2 , –CN, –SCN, or –NO 2 ; X 1 is –C(R c ) 2 O–, –OC(R c ) 2 –, –O–, –N(R c )–, –S–, –C(=O)–, –C(=O)O–, –C(=O)N(R c )–, –OC(=O)–, or –N(R c )C(=O)–; V 1 is =N– or =C(R d )–; each occurrence of R a is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; each occurrence of R b or R c is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group, or two instances of R b , when present, can be joined together with the heteroatom to which they are attached to form an optionally substituted heterocyclic ring; each occurrence of R d is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; n is 0, 1, 2, or 3; and D 1 is a warhead of any one of Formulae (i-1) to (i-43): (i-41) (i-42) (i-43) wherein: L 3 is a bond or an optionally substituted C 1–4 hydrocarbon chain, optionally wherein one or more carbon units of the hydrocarbon chain are independently replaced with –O–, –S–, –NR L3a –, –NR L3a C(=O)–, –C(=O)NR L3a –, –SC(=O)–, –C(=O)S–, –OC(=O)–, –C(=O)O–, –NR L3a C(=S)–, –C(=S)NR L3a –, trans–CR L3b =CR L3b –, cis–CR L3b =CR L3b –, –C≡C–, –S(=O)–, –S(=O)O–, –OS(=O)–, –S(=O)NR L3a –, –NR L3a S(=O)–, –S(=O) 2 –, –S(=O) 2 O–, –OS(=O) 2 –, –S(=O) 2 NR L3a –, or –NR L3a S(=O) 2 –, wherein R L3a is hydrogen, substituted or unsubstituted C 1-6 alkyl, or a nitrogen protecting group, and wherein each occurrence of R L3b is independently selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R L3b groups are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; L 4 is a bond or an optionally substituted C 1 -4 hydrocarbon chain; R E1 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH 2 OR E1a , –CH 2 N(R E1a ) 2 , –CH 2 SR E1a , –OR E1a , –N(R E1a ) 2 , –Si(R E1a ) 3 , and –SR E1a , wherein each occurrence of R E1a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R E1a groups are joined to form an optionally substituted heterocyclic ring; R E2 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH 2 OR E2a , –CH 2 N(R E2a ) 2 , –CH 2 SR E2a , –OR E2a , –N(R E2a ) 2 , and –SR E2a , wherein each occurrence of R E2a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R E2a groups are joined to form an optionally substituted heterocyclic ring; R E3 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH 2 OR E3a , –CH 2 N(R E3a ) 2 , –CH 2 SR E3a , –OR E3a , –N(R E3a ) 2 , and –SR E3a , wherein each occurrence of R E3a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R E3a groups are joined to form an optionally substituted heterocyclic ring; or R E1 and R E3 , or R E2 and R E3 , or R E1 and R E2 are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; R E4 is a leaving group; R E5 is halogen; Y is –O–, –S–, or –NR E6 , wherein R E6 is hydrogen, substituted or unsubstituted C 1-6 alkyl, or a nitrogen protecting group; a is 1 or 2; and each instance of z is independently 0, 1, 2, 3, 4, 5, or 6. [0097] In certain embodiments, a compound of Formula (I’’) is described herein as a compound of Formula (I): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein: Ring A is an optionally substituted 5- or 6-membered heteroaryl comprising at least one nitrogen atom; Ring B is an optionally substituted bicyclic or monocyclic aryl, or an optionally substituted carbocyclic ring; R 1 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –OR a , –N(R b ) 2 , –SR a , –C(=O)R a , –C(=O)OR a , –C(=O)SR a , –C(=O)N(R b ) 2 , –OC(=O)R a , –OC(=O)OR a , –OC(=O)SR a , –OC(=O)N(R b ) 2 , –N(R b )C(=O)R a , –N(R b )C(=O)OR a , –N(R b )C(=O)SR a , –N(R b )C(=O)N(R b ) 2 , –SC(=O)R a , –SC(=O)OR a , –SC(=O)SR a , –SC(=O)N(R b ) 2 , – C(=NR b )R b , –C(=NR b )OR a , –C(=NR b )SR a , –C(=NR b )N(R b ) 2 , –OC(=NR b )R b , – OC(=NR b )OR a , –OC(=NR b )SR a , –OC(=NR b )N(R b ) 2 , –N(R b )C(=NR b )R b , – N(R b )C(=NR b )OR a , –N(R b )C(=NR b )SR a , –N(R b ) C(=NR b )N(R b ) 2 , –SC(=NR b )R b , – SC(=NR b )OR a , –SC(=NR b )SR a , –SC(=NR b )N(R b ) 2 , –C(=S)R a , –C(=S)OR a , –C(=S)SR a , – C(=S)N(R b ) 2 , –S(=O)R a , –SO 2 R a , –NR b SO 2 R a , –SO 2 N(R b ) 2 , –CN, –SCN, or –NO 2 ; X 1 is –O–, –N(R c )–, –S–, –C(=O)–, –C(=O)O–, –C(=O)N(R c )–, –OC(=O)–, or –N(R c )C(=O)–; V 1 is =N– or =C(R d )–; each occurrence of R a is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; each occurrence of R b or R c is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group, or two instances of R b , when present, can be joined together with the heteroatom to which they are attached to form an optionally substituted heterocyclic ring; each occurrence of R d is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; n is 0, 1, 2, or 3; and D 1 is a warhead of any one of Formulae (i-1) to (i-43):
(i-41) (i-42) (i-43) wherein: L 3 is a bond or an optionally substituted C 1–4 hydrocarbon chain, optionally wherein one or more carbon units of the hydrocarbon chain are independently replaced with –O–, –S–, –NR L3a –, –NR L3a C(=O)–, –C(=O)NR L3a –, –SC(=O)–, –C(=O)S–, –OC(=O)–, –C(=O)O–, –NR L3a C(=S)–, –C(=S)NR L3a –, trans–CR L3b =CR L3b –, cis–CR L3b =CR L3b –, –C≡C–, –S(=O)–, –S(=O)O–, –OS(=O)–, –S(=O)NR L3a –, –NR L3a S(=O)–, –S(=O) 2 –, –S(=O) 2 O–, –OS(=O) 2 –, –S(=O) 2 NR L3a –, or –NR L3a S(=O) 2 –, wherein R L3a is hydrogen, substituted or unsubstituted C 1-6 alkyl, or a nitrogen protecting group, and wherein each occurrence of R L3b is independently selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R L3b groups are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; L 4 is a bond or an optionally substituted C 1 -4 hydrocarbon chain; R E1 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH 2 OR E1a , –CH 2 N(R E1a ) 2 , –CH 2 SR E1a , –OR E1a , –N(R E1a ) 2 , –Si(R E1a ) 3 , and –SR E1a , wherein each occurrence of R E1a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R E1a groups are joined to form an optionally substituted heterocyclic ring; R E2 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH 2 OR E2a , –CH 2 N(R E2a ) 2 , –CH 2 SR E2a , –OR E2a , –N(R E2a ) 2 , and –SR E2a , wherein each occurrence of R E2a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R E2a groups are joined to form an optionally substituted heterocyclic ring; R E3 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH 2 OR E3a , –CH 2 N(R E3a ) 2 , –CH 2 SR E3a , –OR E3a , –N(R E3a ) 2 , and –SR E3a , wherein each occurrence of R E3a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R E3a groups are joined to form an optionally substituted heterocyclic ring; or R E1 and R E3 , or R E2 and R E3 , or R E1 and R E2 are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; R E4 is a leaving group; R E5 is halogen; Y is –O–, –S–, or –NR E6 , wherein R E6 is hydrogen, substituted or unsubstituted C 1-6 alkyl, or a nitrogen protecting group; a is 1 or 2; and each instance of z is independently 0, 1, 2, 3, 4, 5, or 6. [0098] In certain embodiments, the compound of Formula (I) is of the Formula (I-a): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [0099] In certain embodiments, the compound of Formula (I) is of the Formula (I-b): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00100] In certain embodiments, the compound of Formula (I) is of the Formula (I-c): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00101] In certain embodiments, the compound of Formula (I) is of the Formula (I-d): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00102] In certain embodiments, the compound of Formula (I) is of the Formula (I-e): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00103] In certain embodiments, the compound of Formula (I) is of the Formula (I-f): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00104] In certain embodiments, the compound of Formula (I) is of the Formula (I-g): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00105] In certain embodiments, the compound of Formula (I) is of the Formula (I-h): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00106] In certain embodiments, the compound of Formula (I) is of the Formula (I-i): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00107] In certain embodiments, the compound of Formula (I) is of the Formula (I-j): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00108] As generally defined herein, Formula (I’’), Formula (I’), or Formula (I) contains Ring A. In certain embodiments, Ring A is an optionally substituted 5- or 6- membered heteroaryl comprising at least one nitrogen atom. In certain embodiments, Ring A is optionally substituted pyrrole. In certain embodiments, Ring A is optionally substituted furan. In certain embodiments, Ring A is optionally substituted thiophene. In certain embodiments, Ring A is optionally substituted imidazole. In certain embodiments, Ring A is optionally substituted pyrazole. In certain embodiments, Ring A is optionally substituted oxazole. In certain embodiments, Ring A is optionally substituted isoxazole. In certain embodiments, Ring A is optionally substituted thiazole. In certain embodiments, Ring A is optionally substituted isothiazole. In certain embodiments, Ring A is optionally substituted triazole. In certain embodiments, Ring A is optionally substituted oxadiazole. In certain embodiments, Ring A is optionally substituted thiadiazole. In certain embodiments, Ring A is optionally substituted tetrazolyl. In certain embodiments, Ring A is optionally substituted pyridine. In certain embodiments, Ring A is optionally substituted pyridazine. In certain embodiments, Ring A is optionally substituted pyrimidine. In certain embodiments, Ring A is or optionally substituted pyrazine. [00109] In certain embodiments, Ring A is of the formula: wherein each instance of R e is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –OR g , –N(R g ) 2 , –SR g , –C(=O)R g , –C(=O)OR g , –C(=O)SR g , –C(=O)N(R g ) 2 , –OC(=O)R g , –OC(=O)OR g , –OC(=O)SR g , –OC(=O)N(R g ) 2 , –N(R g )C(=O)R g , –N(R g )C(=O)OR g , –N(R g )C(=O)SR g , –N(R g )C(=O)N(R g ) 2 , –SC(=O)R g , –SC(=O)OR g , –SC(=O)SR g , –SC(=O)N(R g ) 2 , –C(=NR g )R g , –C(=NR g )OR g , –C(=NR g )SR g , – C(=NR g )N(R g ) 2 , –OC(=NR g )R g , –OC(=NR g )OR g , –OC(=NR g )SR g , –OC(=NR g )N(R g ) 2 , – N(R g )C(=NR g )R g , –N(R g )C(=NR g )OR g , –N(R g )C(=NR g )SR g , –N(R g ) C(=NR g )N(R g ) 2 , – SC(=NR g )R g , –SC(=NR g )OR g , –SC(=NR g )SR g , –SC(=NR g )N(R g ) 2 , –C(=S)R g , –C(=S)OR g , – C(=S)SR g , –C(=S)N(R g ) 2 , –S(=O)R g , –SO 2 R g , –NR g SO 2 R g , –SO 2 N(R g ) 2 , –CN, –SCN, or – NO 2 ; each occurrence of R f or R g is independently D 1 , hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; and p is 0, 1, 2, 3, or 4. [00110] In certain embodiments, Ring A is of the formula: wherein each instance of R e is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –OR g , –N(R g ) 2 , –SR g , –C(=O)R g , –C(=O)OR g , –C(=O)SR g , –C(=O)N(R g ) 2 , –OC(=O)R g , –OC(=O)OR g , –OC(=O)SR g , –OC(=O)N(R g ) 2 , –N(R g )C(=O)R g , –N(R g )C(=O)OR g , –N(R g )C(=O)SR g , –N(R g )C(=O)N(R g ) 2 , –SC(=O)R g , –SC(=O)OR g , –SC(=O)SR g , –SC(=O)N(R g ) 2 , –C(=NR g )R g , –C(=NR g )OR g , –C(=NR g )SR g , – C(=NR g )N(R g ) 2 , –OC(=NR g )R g , –OC(=NR g )OR g , –OC(=NR g )SR g , –OC(=NR g )N(R g ) 2 , –N(R g )C(=NR g )R g , –N(R g )C(=NR g )OR g , –N(R g )C(=NR g )SR g , –N(R g ) C(=NR g )N(R g ) 2 , –SC(=NR g )R g , –SC(=NR g )OR g , –SC(=NR g )SR g , –SC(=NR g )N(R g ) 2 , –C(=S)R g , –C(=S)OR g , –C(=S)SR g , –C(=S)N(R g ) 2 , –S(=O)R g , –SO 2 R g , –NR g SO 2 R g , –SO 2 N(R g ) 2 , –CN, –SCN, or –NO 2 ; each occurrence of R f or R g is independently D 1 , hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; and p is 0, 1, 2, 3, or 4. [00111] In certain embodiments, Ring A is of the formula: In certain embodiments, Ring A is of the formula: In certain embodiments, Ring A is of the formula . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: In certain embodiments, Ring A is of the formula: In certain embodiments, Ring A is of the formula: In certain embodiments, Ring A is of the formula: In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: In certain embodiments, Ring A is of the formula: In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: In certain embodiments, Ring A is of the formula: In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . [00112] As generally defined herein, the compound of Formula (I’’), Formula (I’), or Formula (I) contains the substituent R 1 . In certain embodiments, R 1 is hydrogen. In certain embodiments, R 1 is halogen. In certain embodiments, R 1 is optionally substituted alkyl. In certain embodiments, R 1 is optionally substituted alkenyl. In certain embodiments, R 1 is optionally substituted alkynyl. In certain embodiments, R 1 is optionally substituted carbocyclyl. In certain embodiments, R 1 is optionally substituted heterocyclyl. In certain embodiments, R 1 is optionally substituted aryl. In certain embodiments, R 1 is optionally substituted heteroaryl. In certain embodiments, R 1 is –OR a . In certain embodiments, R 1 is –N(R b ) 2 . In certain embodiments, R 1 is –SR a . In certain embodiments, R 1 is –C(=O)R a . In certain embodiments, R 1 is –C(=O)OR a . In certain embodiments, R 1 is –C(=O)SR a . In certain embodiments, R 1 is –C(=O)N(R b ) 2 . In certain embodiments, R 1 is –OC(=O)R a . In certain embodiments, R 1 is –OC(=O)OR a . In certain embodiments, R 1 is –OC(=O)SR a . In certain embodiments, R 1 is –OC(=O)N(R b ) 2 . In certain embodiments, R 1 is –N(R b )C(=O)R a . In certain embodiments, R 1 is –N(R b )C(=O)OR a . In certain embodiments, R 1 is – N(R b )C(=O)SR a . In certain embodiments, R 1 is –N(R b )C(=O)N(R b ) 2 . In certain embodiments, R 1 is –SC(=O)R a . In certain embodiments, R 1 is –SC(=O)OR a . In certain embodiments, R 1 is –SC(=O)SR a . In certain embodiments, R 1 is –SC(=O)N(R b ) 2 . In certain embodiments, R 1 is – C(=NR b )R b . In certain embodiments, R 1 is –C(=NR b )OR a . In certain embodiments, R 1 is – C(=NR b )SR a . In certain embodiments, R 1 is –C(=NR b )N(R b ) 2 . In certain embodiments, R 1 is – OC(=NR b )R b . In certain embodiments, R 1 is –OC(=NR b )OR a . In certain embodiments, R 1 is – OC(=NR b )SR a . In certain embodiments, R 1 is –OC(=NR b )N(R b ) 2 . In certain embodiments, R 1 is –N(R b )C(=NR b )R b . In certain embodiments, R 1 is –N(R b )C(=NR b )OR a . In certain embodiments, R 1 is –N(R b )C(=NR b )SR a . In certain embodiments, R 1 is – N(R b )C(=NR b )N(R b ) 2 . In certain embodiments, R 1 is –SC(=NR b )R b . In certain embodiments, R 1 is –SC(=NR b )OR a . In certain embodiments, R 1 is –SC(=NR b )SR a . In certain embodiments, R 1 is –SC(=NR b )N(R b ) 2 . In certain embodiments, R 1 is –C(=S)R a . In certain embodiments, R 1 is –C(=S)OR a . In certain embodiments, R 1 is –C(=S)SR a . In certain embodiments, R 1 is –C(=S)N(R b ) 2 . In certain embodiments, R 1 is –S(=O)R a . In certain embodiments, R 1 is – SO 2 R a . In certain embodiments, R 1 is –NR b SO 2 R a . In certain embodiments, R 1 is –SO 2 N(R b ) 2 . In certain embodiments, R 1 is –CN or –SCN. In certain embodiments, R 1 is –NO 2 . [00113] In certain embodiments, the substituent R 1 contains the substituent R a . In certain embodiments, each occurrence of R a , when present, is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom. In certain embodiments, R a is hydrogen. In certain embodiments, R a is optionally substituted alkyl. In certain embodiments, R a is optionally substituted alkenyl. In certain embodiments, R a is optionally substituted alkynyl. In certain embodiments, R a is optionally substituted carbocyclyl. In certain embodiments, R a is optionally substituted heterocyclyl. In certain embodiments, R a is optionally substituted aryl. In certain embodiments, R a is optionally substituted heteroaryl. In certain embodiments, R a is an oxygen protecting group when attached to an oxygen atom. In certain embodiments, R a is a sulfur protecting group when attached to a sulfur atom. [00114] In certain embodiments, the substituent R 1 contains the substituent R b . In certain embodiments, each occurrence of R b , when present, is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group, or two instances of R b , when present, can be joined together with the heteroatom to which they are attached to form an optionally substituted heterocyclic ring. In certain embodiments, each occurrence of R b , when present, is independently hydrogen. In certain embodiments, each occurrence of R b , when present, is independently optionally substituted alkyl. In certain embodiments, each occurrence of R b , when present, is independently optionally substituted alkenyl. In certain embodiments, each occurrence of R b , when present, is independently optionally substituted alkynyl. In certain embodiments, each occurrence of R b , when present, is independently optionally substituted carbocyclyl. In certain embodiments, each occurrence of R b , when present, is independently optionally substituted heterocyclyl. In certain embodiments, each occurrence of R b , when present, is independently optionally substituted aryl. In certain embodiments, each occurrence of R b , when present, is independently optionally substituted heteroaryl. In certain embodiments, each occurrence of R b , when present, is independently a nitrogen protecting group. In certain embodiments, two instances of R b , when present, can be joined together with the heteroatom to which they are attached to form an optionally substituted heterocyclic ring. [00115] As generally defined herein, Formula (I’’), Formula (I’), or Formula (I) contains the substituent X 1 . In certain embodiments, X 1 is –CH 2 O–. In certain embodiments, X 1 is – OCH 2 –. In certain embodiments, X 1 is –O–, –N(R c )–, –S–, –C(=O)–, –C(=O)O–, –C(=O)N(R c )–, –OC(=O)–, or –N(R c )C(=O)–. In certain embodiments, X 1 is –O–. In certain embodiments, X 1 is –S–. In certain embodiments, X 1 is –C(=O)–. In certain embodiments, X 1 is –C(=O)O–. In certain embodiments, X 1 is –C(=O)N(R c )–. In certain embodiments, X 1 is –OC(=O)–. In certain embodiments, X 1 is –N(R c )C(=O)–. In certain embodiments, X 1 is –N(R c )–. In certain embodiments, X 1 is –N(H)–. In certain embodiments, X 1 is –N(Me)–. [00116] In certain embodiments, the substituent X 1 contains the substituent R c . In certain embodiments, each occurrence of R c , when present, is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group. In certain embodiments, each occurrence of R c , when present, is independently hydrogen. In certain embodiments, each occurrence of R c , when present, is independently optionally substituted alkyl. In certain embodiments, each occurrence of R c , when present, is independently optionally substituted alkenyl. In certain embodiments, each occurrence of R c , when present, is independently optionally substituted alkynyl. In certain embodiments, each occurrence of R c , when present, is independently optionally substituted carbocyclyl. In certain embodiments, each occurrence of R c , when present, is independently optionally substituted heterocyclyl. In certain embodiments, each occurrence of R c , when present, is independently optionally substituted aryl. In certain embodiments, each occurrence of R c , when present, is independently optionally substituted heteroaryl. In certain embodiments, each occurrence of R c , when present, is independently a nitrogen protecting group. [00117] As generally defined herein, the compound of Formula (I’’), Formula (I’), or Formula (I) contains the substituent V 1 . In certain embodiments, V 1 is =N– or =C(R 1 )–. In certain embodiments, V 1 is =N–. In certain embodiments, V 1 is =C(R 1 )–. In certain embodiments, V 1 is =C(H)–. [00118] In certain embodiments, n is 0. In certain embodiments, n is 1. In certain embodiments, n is 2. In certain embodiments, n is 3. [00119] In certain embodiments, a compound described herein is of Formula (II’): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein: Ring A is an optionally substituted 5- or 6-membered heteroaryl comprising at least one nitrogen atom, or a bicyclic heteroaryl; Ring B is an optionally substituted bicyclic or monocyclic aryl, or an optionally substituted carbocyclic ring; R 2 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –OR a , –N(R b ) 2 , –SR a , –C(=O)R a , –C(=O)OR a , –C(=O)SR a , –C(=O)N(R b ) 2 , –OC(=O)R a , –OC(=O)OR a , –OC(=O)SR a , –OC(=O)N(R b ) 2 , –N(R b )C(=O)R a , –N(R b )C(=O)OR a , –N(R b )C(=O)SR a , –N(R b )C(=O)N(R b ) 2 , –SC(=O)R a , –SC(=O)OR a , –SC(=O)SR a , –SC(=O)N(R b ) 2 , – C(=NR b )R b , –C(=NR b )OR a , –C(=NR b )SR a , –C(=NR b )N(R b ) 2 , –OC(=NR b )R b , – OC(=NR b )OR a , –OC(=NR b )SR a , –OC(=NR b )N(R b ) 2 , –N(R b )C(=NR b )R b , – N(R b )C(=NR b )OR a , –N(R b )C(=NR b )SR a , –N(R b ) C(=NR b )N(R b ) 2 , –SC(=NR b )R b , – SC(=NR b )OR a , –SC(=NR b )SR a , –SC(=NR b )N(R b ) 2 , –C(=S)R a , –C(=S)OR a , –C(=S)SR a , – C(=S)N(R b ) 2 , –S(=O)R a , –SO 2 R a , –NR b SO 2 R a , –SO 2 N(R b ) 2 , –CN, –SCN, or –NO 2 ; X 2 is a bond, –C(R c ) 2 –; –CO–, –OC(R c ) 2 –, –O–, –N(R c )–, –S–, –C(=O)–, –C(=O)O–, –C(=O)N(R c )–, –OC(=O)–, or –N(R c )C(=O)–; each occurrence of R a is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; each occurrence of R b or R c is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group, or two instances of R b , when present, can be joined together with the heteroatom to which they are attached to form an optionally substituted heterocyclic ring; m is 0, 1, 2, 3, or 4; and D 1 is a warhead of any one of Formulae (i-1) to (i-43):
(i-41) (i-42) (i-43) wherein: L 3 is a bond or an optionally substituted C 1–4 hydrocarbon chain, optionally wherein one or more carbon units of the hydrocarbon chain are independently replaced with –O–, –S–, –NR L3a –, –NR L3a C(=O)–, –C(=O)NR L3a –, –SC(=O)–, –C(=O)S–, –OC(=O)–, –C(=O)O–, –NR L3a C(=S)–, –C(=S)NR L3a –, trans–CR L3b =CR L3b –, cis–CR L3b =CR L3b –, –C≡C–, –S(=O)–, –S(=O)O–, –OS(=O)–, –S(=O)NR L3a –, –NR L3a S(=O)–, –S(=O) 2 –, –S(=O) 2 O–, –OS(=O) 2 –, –S(=O) 2 NR L3a –, or –NR L3a S(=O) 2 –, wherein R L3a is hydrogen, substituted or unsubstituted C 1-6 alkyl, or a nitrogen protecting group, and wherein each occurrence of R L3b is independently selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R L3b groups are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; L 4 is a bond or an optionally substituted C 1-4 hydrocarbon chain; R E1 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH 2 OR E1a , –CH 2 N(R E1a ) 2 , –CH 2 SR E1a , –OR E1a , –N(R E1a ) 2 , –Si(R E1a )3, and –SR E1a , wherein each occurrence of R E1a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R E1a groups are joined to form an optionally substituted heterocyclic ring; R E2 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH 2 OR E2a , –CH 2 N(R E2a ) 2 , –CH 2 SR E2a , –OR E2a , –N(R E2a ) 2 , and –SR E2a , wherein each occurrence of R E2a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R E2a groups are joined to form an optionally substituted heterocyclic ring; R E3 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH 2 OR E3a , –CH 2 N(R E3a ) 2 , –CH 2 SR E3a , –OR E3a , –N(R E3a ) 2 , and –SR E3a , wherein each occurrence of R E3a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R E3a groups are joined to form an optionally substituted heterocyclic ring; or R E1 and R E3 , or R E2 and R E3 , or R E1 and R E2 are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; R E4 is a leaving group; R E5 is halogen; Y is –O–, –S–, or –NR E6 , wherein R E6 is hydrogen, substituted or unsubstituted C 1-6 alkyl, or a nitrogen protecting group; a is 1 or 2; and each instance of z is independently 0, 1, 2, 3, 4, 5, or 6. [00120] In certain embodiments, the compound of Formula (II’) is of the Formula (II’-a): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00121] In certain embodiments, the compound of Formula (II’) is of the Formula (II’-b): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00122] In certain embodiments, a compound of Formula (II’) as described herein is of Formula (II): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein: Ring A is an optionally substituted 5- or 6-membered heteroaryl comprising at least one nitrogen atom; Ring B is an optionally substituted bicyclic or monocyclic aryl, or an optionally substituted carbocyclic ring; R 2 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –OR a , –N(R b ) 2 , – SR a , –C(=O)R a , –C(=O)OR a , –C(=O)SR a , –C(=O)N(R b ) 2 , –OC(=O)R a , –OC(=O)OR a , – OC(=O)SR a , –OC(=O)N(R b ) 2 , –N(R b )C(=O)R a , –N(R b )C(=O)OR a , –N(R b )C(=O)SR a , – N(R b )C(=O)N(R b ) 2 , SC(=O)R a , –SC(=O)OR a , –SC(=O)SR a , –SC(=O)N(R b ) 2 , –C(=NR b )R b , – C(=NR b )OR a , –C(=NR b )SR a , –C(=NR b )N(R b ) 2 , –OC(=NR b )R b , –OC(=NR b )OR a , – OC(=NR b )SR a , –OC(=NR b )N(R b ) 2 , –N(R b )C(=NR b )R b , –N(R b )C(=NR b )OR a , – N(R b )C(=NR b )SR a , –N(R b ) C(=NR b )N(R b ) 2 , –SC(=NR b )R b , –SC(=NR b )OR a , –SC(=NR b )SR a , –SC(=NR b )N(R b ) 2 , –C(=S)R a , –C(=S)OR a , –C(=S)SR a , –C(=S)N(R b ) 2 , –S(=O)R a , –SO 2 R a , – NR b SO 2 R a , –SO 2 N(R b ) 2 , –CN, –SCN, or –NO 2 ; X 2 is –O–, –N(R c )–, –S–, –C(=O)–, –C(=O)O–, –C(=O)N(R c )–, –OC(=O)–, or –N(R c )C(=O)–; each occurrence of R a is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; each occurrence of R b or R c is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, a nitrogen protecting group, or two instances of R b , when present, can be joined together with the heteroatom to which they are attached to form an optionally substituted heterocyclic ring; m is 0, 1, 2, 3, or 4; and D 1 is a warhead of any one of Formulae (i-1) to (i-43):
(i-41) (i-42) (i-43) wherein: L 3 is a bond or an optionally substituted C 1–4 hydrocarbon chain, optionally wherein one or more carbon units of the hydrocarbon chain are independently replaced with –O–, –S–, –NR L3a –, –NR L3a C(=O)–, –C(=O)NR L3a –, –SC(=O)–, –C(=O)S–, –OC(=O)–, –C(=O)O–, –NR L3a C(=S)–, –C(=S)NR L3a –, trans–CR L3b =CR L3b –, cis–CR L3b =CR L3b –, –C≡C–, –S(=O)–, –S(=O)O–, –OS(=O)–, –S(=O)NR L3a –, –NR L3a S(=O)–, –S(=O) 2 –, –S(=O) 2 O–, –OS(=O) 2 –, –S(=O) 2 NR L3a –, or –NR L3a S(=O) 2 –, wherein R L3a is hydrogen, substituted or unsubstituted C 1-6 alkyl, or a nitrogen protecting group, and wherein each occurrence of R L3b is independently selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R L3b groups are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; L 4 is a bond or an optionally substituted C 1-4 hydrocarbon chain; R E1 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH 2 OR E1a , –CH 2 N(R E1a ) 2 , –CH 2 SR E1a , –OR E1a , –N(R E1a ) 2 , –Si(R E1a )3, and –SR E1a , wherein each occurrence of R E1a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R E1a groups are joined to form an optionally substituted heterocyclic ring; R E2 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH 2 OR E2a , –CH 2 N(R E2a ) 2 , –CH 2 SR E2a , –OR E2a , –N(R E2a ) 2 , and –SR E2a , wherein each occurrence of R E2a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R E2a groups are joined to form an optionally substituted heterocyclic ring; R E3 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH 2 OR E3a , –CH 2 N(R E3a ) 2 , –CH 2 SR E3a , –OR E3a , –N(R E3a ) 2 , and –SR E3a , wherein each occurrence of R E3a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R E3a groups are joined to form an optionally substituted heterocyclic ring; or R E1 and R E3 , or R E2 and R E3 , or R E1 and R E2 are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; R E4 is a leaving group; R E5 is halogen; Y is –O–, –S–, or –NR E6 –, wherein R E6 is hydrogen, substituted or unsubstituted C 1-6 alkyl, or a nitrogen protecting group; a is 1 or 2; and each instance of z is independently 0, 1, 2, 3, 4, 5, or 6. [00123] In certain embodiments, the compound of Formula (II) is of the Formula (II-a): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00124] In certain embodiments, the compound of Formula (II) is of the Formula (II-b): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00125] Formula (II’) contains Ring A. In certain embodiments, Ring A is an optionally substituted 5- or 6-membered heteroaryl comprising at least one nitrogen atom. In certain embodiments, Ring A is an optionally substituted pyrrole, optionally substituted furan, optionally substituted thiophene, optionally substituted imidazole, optionally substituted pyrazole, optionally substituted oxazole, optionally substituted isoxazole, optionally substituted thiazole, optionally substituted isothiazole, optionally substituted triazole, optionally substituted oxadiazole, optionally substituted thiadiazole, optionally substituted tetrazolyl, optionally substituted pyridine, optionally substituted pyridazine, optionally substituted pyrimidine, or optionally substituted pyrazine. In certain embodiments, Ring A is of the formula: wherein each instance of R e is independently D 1 , hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –OR g , –N(R g ) 2 , –SR g , –C(=O)R g , –C(=O)OR g , –C(=O)SR g , –C(=O)N(R g ) 2 , –OC(=O)R g , –OC(=O)OR g , –OC(=O)SR g , –OC(=O)N(R g ) 2 , –N(R g )C(=O)R g , –N(R g )C(=O)OR g , –N(R g )C(=O)SR g , –N(R g )C(=O)N(R g ) 2 , –SC(=O)R g , –SC(=O)OR g , –SC(=O)SR g , –SC(=O)N(R g ) 2 , –C(=NR g )R g , –C(=NR g )OR g , –C(=NR g )SR g , – C(=NR g )N(R g ) 2 , –OC(=NR g )R g , –OC(=NR g )OR g , –OC(=NR g )SR g , –OC(=NR g )N(R g ) 2 , –N(R g )C(=NR g )R g , –N(R g )C(=NR g )OR g , –N(R g )C(=NR g )SR g , –N(R g ) C(=NR g )N(R g ) 2 , –SC(=NR g )R g , –SC(=NR g )OR g , –SC(=NR g )SR g , –SC(=NR g )N(R g ) 2 , –C(=S)R g , –C(=S)OR g , –C(=S)SR g , –C(=S)N(R g ) 2 , –S(=O)R g , –SO 2 R g , –NR g SO 2 R g , –SO 2 N(R g ) 2 , –CN, –SCN, or –NO 2 ; each occurrence of R f or R g is independently D 1 , hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; and p is 0, 1, 2, 3, or 4. [00126] In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . In certain embodiments, Ring A is of the formula: . [00127] Formula (II’) contains the substituent R 2 . In certain embodiments, at least one instance of R 2 is hydrogen. In certain embodiments, at least one instance of R 2 is halogen. In certain embodiments, at least one instance of R 2 is optionally substituted alkyl. In certain embodiments, at least one instance of R 2 is optionally substituted alkenyl. In certain embodiments, at least one instance of R 2 is optionally substituted alkynyl. In certain embodiments, at least one instance of R 2 is optionally substituted carbocyclyl. In certain embodiments, at least one instance of R 2 is optionally substituted heterocyclyl. In certain embodiments, at least one instance of R 2 is optionally substituted aryl. In certain embodiments, at least one instance of R 2 is optionally substituted heteroaryl. In certain embodiments, at least one instance of R 2 is –OR a . In certain embodiments, at least one instance of R 2 is –N(R b ) 2 . In certain embodiments, at least one instance of R 2 is –SR a . In certain embodiments, at least one instance of R 2 is –C(=O)R a . In certain embodiments, at least one instance of R 2 is –C(=O)OR a . In certain embodiments, at least one instance of R 2 is –C(=O)SR a . In certain embodiments, at least one instance of R 2 is –C(=O)N(R b ) 2 . In certain embodiments, at least one instance of R 2 is –OC(=O)R a . In certain embodiments, at least one instance of R 2 is –OC(=O)OR a . In certain embodiments, at least one instance of R 2 is – OC(=O)SR a . In certain embodiments, at least one instance of R 2 is –OC(=O)N(R b ) 2 . In certain embodiments, at least one instance of R 2 is –N(R b )C(=O)R a . In certain embodiments, at least one instance of R 2 is –N(R b )C(=O)OR a . In certain embodiments, at least one instance of R 2 is –N(R b )C(=O)SR a . In certain embodiments, at least one instance of R 2 is – N(R b )C(=O)N(R b ) 2 . In certain embodiments, at least one instance of R 2 is –SC(=O)R a . In certain embodiments, at least one instance of R 2 is –SC(=O)OR a . In certain embodiments, at least one instance of R 2 is –SC(=O)SR a . In certain embodiments, at least one instance of R 2 is –SC(=O)N(R b ) 2 . In certain embodiments, at least one instance of R 2 is –C(=NR b )R b . In certain embodiments, at least one instance of R 2 is –C(=NR b )OR a . In certain embodiments, at least one instance of R 2 is –C(=NR b )SR a . In certain embodiments, at least one instance of R 2 is –C(=NR b )N(R b ) 2 . In certain embodiments, at least one instance of R 2 is –OC(=NR b )R b . In certain embodiments, at least one instance of R 2 is –OC(=NR b )OR a . In certain embodiments, at least one instance of R 2 is –OC(=NR b )SR a . In certain embodiments, at least one instance of R 2 is –OC(=NR b )N(R b ) 2 . In certain embodiments, at least one instance of R 2 is – N(R b )C(=NR b )R b . In certain embodiments, at least one instance of R 2 is –N(R b )C(=NR b )OR a . In certain embodiments, at least one instance of R 2 is –N(R b )C(=NR b )SR a . In certain embodiments, at least one instance of R 2 is –N(R b )C(=NR b )N(R b ) 2 . In certain embodiments, at least one instance of R 2 is –SC(=NR b )R b . In certain embodiments, at least one instance of R 2 is –SC(=NR b )OR a . In certain embodiments, at least one instance of R 2 is –SC(=NR b )SR a . In certain embodiments, at least one instance of R 2 is –SC(=NR b )N(R b ) 2 . In certain embodiments, at least one instance of R 2 is –C(=S)R a . In certain embodiments, at least one instance of R 2 is –C(=S)OR a . In certain embodiments, at least one instance of R 2 is – C(=S)SR a . In certain embodiments, at least one instance of R 2 is –C(=S)N(R b ) 2 . In certain embodiments, at least one instance of R 2 is –S(=O)R a . In certain embodiments, at least one instance of R 2 is –SO 2 R a . In certain embodiments, at least one instance of at least one instance of R 2 is –NR b SO 2 R a . In certain embodiments, at least one instance of R 2 is –SO 2 N(R b ) 2 . In certain embodiments, at least one instance of R 2 is –CN. In certain embodiments, at least one instance of R 2 is –SCN. In certain embodiments, at least one instance of R 2 is –NO 2 . [00128] In certain embodiments, the substituent R 2 contains the substituent R a . In certain embodiments, each occurrence of R a , when present, is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom. In certain embodiments, R a is hydrogen. In certain embodiments, R a is optionally substituted alkyl. In certain embodiments, R a is optionally substituted alkenyl. In certain embodiments, R a is optionally substituted alkynyl. In certain embodiments, R a is optionally substituted carbocyclyl. In certain embodiments, R a is optionally substituted heterocyclyl. In certain embodiments, R a is optionally substituted aryl. In certain embodiments, R a is optionally substituted heteroaryl. In certain embodiments, R a is an oxygen protecting group when attached to an oxygen atom. In certain embodiments, R a is a sulfur protecting group when attached to a sulfur atom. [00129] As generally defined herein, Formula (II’) contains the substituent X 2 . In certain embodiments, X 2 is –O–. In certain embodiments, X 2 is –N(R c )–. In certain embodiments, X 2 is –S–. In certain embodiments, X 2 is –C(=O)–. In certain embodiments, X 2 is –C(=O)O–. In certain embodiments, X 2 is –C(=O)N(R c )–. In certain embodiments, X 2 is –OC(=O)–. In certain embodiments, X 2 is –N(R c )C(=O)–. In certain embodiments, X 2 is –N(H)–. [00130] In certain embodiments, each occurrence of R b or R c , when present, is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group, or two instances of R b , when present, can be joined together with the heteroatom to which they are attached to form an optionally substituted heterocyclic ring. In certain embodiments, each occurrence of R b or R c , when present, is independently hydrogen. In certain embodiments, each occurrence of R b or R c , when present, is independently optionally substituted alkyl. In certain embodiments, each occurrence of R b or R c , when present, is independently optionally substituted alkenyl. In certain embodiments, each occurrence of R b or R c , when present, is independently optionally substituted alkynyl. In certain embodiments, each occurrence of R b or R c , when present, is independently optionally substituted carbocyclyl. In certain embodiments, each occurrence of R b or R c , when present, is independently optionally substituted heterocyclyl. In certain embodiments, each occurrence of R b or R c , when present, is independently optionally substituted aryl. In certain embodiments, each occurrence of R b or R c , when present, is independently optionally substituted heteroaryl. In certain embodiments, each occurrence of R b or R c , when present, is independently a nitrogen protecting group. In certain embodiments, two instances of R b , when present, can be joined together with the heteroatom to which they are attached to form an optionally substituted heterocyclic ring. [00131] In certain embodiments, m is 0. In certain embodiments, m is 1. In certain embodiments, m is 2. In certain embodiments, m is 3. In certain embodiments, m is 4. [00132] As generally defined herein, Formula (I’’), Formula (I’), Formula (I), Formula (II’), and Formula (II) contain Ring B. In certain embodiments, Ring B is an optionally substituted bicyclic or monocyclic aryl, or an optionally substituted carbocyclic ring. In certain embodiments, Ring B is an optionally substituted bicyclic or monocyclic aryl. In certain embodiments, Ring B is an optionally substituted carbocyclic ring. In certain embodiments, Ring B is an optionally substituted phenyl. [00133] In certain embodiments, Ring B is of the formula: wherein each instance of R h is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –OR i , –N(R i ) 2 , –SR i , –C(=O)R i , –C(=O)OR i , –C(=O)SR i , –C(=O)N(R i ) 2 , – OC(=O)R i , –OC(=O)OR i , –OC(=O)SR i , –OC(=O)N(R i ) 2 , –N(R i )C(=O)R i , –N(R i )C(=O)OR i , –N(R i )C(=O)SR i , –N(R i )C(=O)N(R i ) 2 , –SC(=O)R i , –SC(=O)OR i , –SC(=O)SR i , – SC(=O)N(R i ) 2 , –C(=NR i )R i , –C(=NR i )OR i , –C(=NR i )SR i , –C(=NR i )N(R i ) 2 , –OC(=NR i )R i , – OC(=NR i )OR i , –OC(=NR i )SR i , –OC(=NR i )N(R i ) 2 , –N(R i )C(=NR i )R i , –N(R i )C(=NR i )OR i , – N(R i )C(=NR i )SR i , –N(R i ) C(=NR i )N(R i ) 2 , –SC(=NR i )R i , –SC(=NR i )OR i , –SC(=NR i )SR i , – SC(=NR i )N(R i ) 2 , –C(=S)R i , –C(=S)OR i , –C(=S)SR i , –C(=S)N(R i ) 2 , –S(=O)R i , –SO 2 R i , – NR i SO 2 R i , –SO 2 N(R i ) 2 , –CN, –SCN, or –NO 2 ; each occurrence of R i is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; and r is 0, 1, 2, 3, 4, 5, 6, 7, or 8. [00134] In certain embodiments, at least on instance of R h is independently hydrogen. In certain embodiments, at least on instance of R h is independently halogen. In certain embodiments, at least on instance of R h is independently optionally substituted alkyl. In certain embodiments, at least on instance of R h is independently optionally substituted alkenyl. In certain embodiments, at least on instance of R h is independently optionally substituted alkynyl. In certain embodiments, at least on instance of R h is independently optionally substituted carbocyclyl. In certain embodiments, at least on instance of R h is independently optionally substituted heterocyclyl. In certain embodiments, at least on instance of R h is independently optionally substituted aryl. In certain embodiments, at least on instance of R h is independently optionally substituted heteroaryl. In certain embodiments, at least on instance of R h is independently –OR i . In certain embodiments, at least on instance of R h is independently –N(R i ) 2 . In certain embodiments, at least on instance of R h is independently –SR i . In certain embodiments, at least on instance of R h is independently –C(=O)R i . In certain embodiments, at least on instance of R h is independently –C(=O)OR i . In certain embodiments, at least on instance of R h is independently –C(=O)SR i . In certain embodiments, at least on instance of R h is independently –C(=O)N(R i ) 2 . In certain embodiments, at least on instance of R h is independently –OC(=O)R i . In certain embodiments, at least on instance of R h is independently –OC(=O)OR i . In certain embodiments, at least on instance of R h is independently –OC(=O)SR i . In certain embodiments, at least on instance of R h is independently –OC(=O)N(R i ) 2 . In certain embodiments, at least on instance of R h is independently –N(R i )C(=O)R i . In certain embodiments, at least on instance of R h is independently –N(R i )C(=O)OR i . In certain embodiments, at least on instance of R h is independently –N(R i )C(=O)SR i . In certain embodiments, at least on instance of R h is independently –N(R i )C(=O)N(R i ) 2 . In certain embodiments, at least on instance of R h is independently –SC(=O)R i . In certain embodiments, at least on instance of R h is independently –SC(=O)OR i . In certain embodiments, at least on instance of R h is independently –SC(=O)SR i . In certain embodiments, at least on instance of R h is independently –SC(=O)N(R i ) 2 . In certain embodiments, at least on instance of R h is independently –C(=NR i )R i . In certain embodiments, at least on instance of R h is independently –C(=NR i )OR i . In certain embodiments, at least on instance of R h is independently –C(=NR i )SR i . In certain embodiments, at least on instance of R h is independently –C(=NR i )N(R i ) 2 . In certain embodiments, at least on instance of R h is independently –OC(=NR i )R i . In certain embodiments, at least on instance of R h is independently –OC(=NR i )OR i . In certain embodiments, at least on instance of R h is independently –OC(=NR i )SR i . In certain embodiments, at least on instance of R h is independently –OC(=NR i )N(R i ) 2 . In certain embodiments, at least on instance of R h is independently –N(R i )C(=NR i )R i . In certain embodiments, at least on instance of R h is independently –N(R i )C(=NR i )OR i . In certain embodiments, at least on instance of R h is independently –N(R i )C(=NR i )SR i . In certain embodiments, at least on instance of R h is independently –N(R i )C(=NR i )N(R i ) 2 . In certain embodiments, at least on instance of R h is independently –SC(=NR i )R i . In certain embodiments, at least on instance of R h is independently –SC(=NR i )OR i . In certain embodiments, at least on instance of R h is independently –SC(=NR i )SR i . In certain embodiments, at least on instance of R h is independently –SC(=NR i )N(R i ) 2 . In certain embodiments, at least on instance of R h is independently –C(=S)R i . In certain embodiments, at least on instance of R h is independently –C(=S)OR i . In certain embodiments, at least on instance of R h is independently –C(=S)SR i . In certain embodiments, at least on instance of R h is independently –C(=S)N(R i ) 2 . In certain embodiments, at least on instance of R h is independently –S(=O)R i . In certain embodiments, at least on instance of R h is independently –SO 2 R i . In certain embodiments, at least on instance of R h is independently –NR i SO 2 R i . In certain embodiments, at least on instance of R h is independently –SO 2 N(R i ) 2 . In certain embodiments, at least on instance of R h is independently –CN. In certain embodiments, at least on instance of R h is independently –SCN. In certain embodiments, at least on instance of R h is independently –NO 2 . [00135] In certain embodiments, R h contains the substituent R i . In certain embodiments, each occurrence of R i , when present, is independently hydrogen. In certain embodiments, each occurrence of R i , when present, is independently optionally substituted alkyl. In certain embodiments, each occurrence of R i , when present, is independently optionally substituted alkenyl. In certain embodiments, each occurrence of R i , when present, is independently optionally substituted alkynyl. In certain embodiments, each occurrence of R i , when present, is independently optionally substituted carbocyclyl. In certain embodiments, each occurrence of R i , when present, is independently optionally substituted heterocyclyl. In certain embodiments, each occurrence of R i , when present, is independently optionally substituted aryl. In certain embodiments, each occurrence of R i , when present, is independently optionally substituted heteroaryl. In certain embodiments, each occurrence of R i , when present, is independently an oxygen protecting group when attached to an oxygen atom. In certain embodiments, each occurrence of R i , when present, is independently a sulfur protecting group when attached to a sulfur atom. [00136] In certain embodiments, r is 0. In certain embodiments, r is 1. In certain embodiments, r is 2. In certain embodiments, r is 3. In certain embodiments, r is 4. In certain embodiments, r is 5. In certain embodiments, r is 6. In certain embodiments, r is 7. In certain embodiments, r is 8. [00137] In certain embodiments, Ring B is of the formula: . In certain embodiments, Ring B is of the formula: . [00138] In certain embodiments, Ring B is an optionally substituted carbocyclic ring. In certain embodiments, Ring B is an optionally substituted cyclohexyl ring. In certain embodiments, Ring B is of the formula: , wherein each instance of R h is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –OR i , –N(R i ) 2 , – SR i , –C(=O)R i , –C(=O)OR i , –C(=O)SR i , –C(=O)N(R i ) 2 , –OC(=O)R i , –OC(=O)OR i , – OC(=O)SR i , –OC(=O)N(R i ) 2 , –N(R i )C(=O)R i , –N(R i )C(=O)OR i , –N(R i )C(=O)SR i , – N(R i )C(=O)N(R i ) 2 , –SC(=O)R i , –SC(=O)OR i , –SC(=O)SR i , –SC(=O)N(R i ) 2 , –C(=NR i )R i , – C(=NR i )OR i , –C(=NR i )SR i , –C(=NR i )N(R i ) 2 , –OC(=NR i )R i , –OC(=NR i )OR i , – OC(=NR i )SR i , –OC(=NR i )N(R i ) 2 , –N(R i )C(=NR i )R i , –N(R i )C(=NR i )OR i , –N(R i )C(=NR i )SR i , –N(R i ) C(=NR i )N(R i ) 2 , –SC(=NR i )R i , –SC(=NR i )OR i , –SC(=NR i )SR i , –SC(=NR i )N(R i ) 2 , – C(=S)R i , –C(=S)OR i , –C(=S)SR i , –C(=S)N(R i ) 2 , –S(=O)R i , –SO 2 R i , –NR i SO 2 R i , –SO 2 N(R i ) 2 , –CN, –SCN, or –NO 2 ; each occurrence of R i is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; and r is 0, 1, 2, 3, 4, 5, 6, 7, or 8. [00139] In certain embodiments, Ring B is of the formula: [00140] As generally defined herein, Formula (I’’), Formula (I’), Formula (I), and Formula (II) include the substituent D 1 , wherein D 1 is a warhead of any one of Formulae (i-1) to (i-43): (i-11) (i-12) (i-13) (i-14) (i-15) (i-41) (i-42) (i-43) wherein: L 3 is a bond or an optionally substituted C 1–4 hydrocarbon chain, optionally wherein one or more carbon units of the hydrocarbon chain are independently replaced with –C=O–, – O–, –S–, –NR L3a –, –NR L3a C(=O)–, –C(=O)NR L3a –, –SC(=O)–, –C(=O)S–, –OC(=O)–, – C(=O)O–, –NR L3a C(=S)–, –C(=S)NR L3a –, trans–CR L3b =CR L3b –, cis–CR L3b =CR L3b –, –C≡C–, –S(=O)–, –S(=O)O–, –OS(=O)–, –S(=O)NR L3a –, –NR L3a S(=O)–, –S(=O) 2 –, –S(=O) 2 O–, – OS(=O) 2 –, –S(=O) 2 NR L3a –, or –NR L3a S(=O) 2 –, wherein R L3a is hydrogen, substituted or unsubstituted C 1–6 alkyl, or a nitrogen protecting group, and wherein each occurrence of R L3b is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or two R L3b groups are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; L 4 is a bond or an optionally substituted, branched or unbranched C 1–6 hydrocarbon chain; each of R E1 , R E2 , and R E3 is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, –CN, –CH 2 OR EE , –CH 2 N(R EE ) 2 , –CH 2 SR EE , –OR EE , –N(R EE ) 2 , –Si(R EE )3, or –SR EE , wherein each instance of R EE is independently hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or two R EE groups are joined to form an optionally substituted heterocyclic ring; or R E1 and R E3 , or R E2 and R E3 , or R E1 and R E2 are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; R E4 is a leaving group; R E5 is halogen; R E6 is hydrogen, substituted or unsubstituted C 1–6 alkyl, or a nitrogen protecting group; each instance of Y is independently O, S, or NR E7 , wherein R E7 is hydrogen, substituted or unsubstituted C 1–6 alkyl, or a nitrogen protecting group; a is 1 or 2; and each instance of z is independently 0, 1, 2, 3, 4, 5, or 6, as valency permits. [00141] In certain embodiments, D 1 is a warhead of formula (i-1). In certain embodiments, D 1 is a warhead of formula: . In certain embodiments, D 1 is a warhead of formula: . In certain embodiments, D 1 is a warhead of formula: In certain embodiments, D 1 is of formula: or . In certain embodi 1 ments, D is of formula: [00142] In certain embodiments, L3 is a bond. In certain embodiments, L3 is –NH–. In certain embodiments, R E1 and R E2 are hydrogen. In certain embodiments, R E1 , R E2 , and R E3 are all hydrogen. In certain embodiments, R E3 is –CH 2 NMe2. [00143] In certain embodiments, the warhead is of formula: (i-2). In certain embodiments, the warhead is of formula: (i-3). In certain embodiments, the warhead is of formula: (i-4). In certain embodiments, the warhead is of formula: (i-5). In certain embodiments, the warhead is of formula: (i-6). In certain embodiments, the warhead is of formula: (i-7). In certain embodiments, the warhead is of formula: (i-8). In certain embodiments, the warhead is of formula: (i- 9). In certain embodiments, the warhead is of formula: (i-10). In certain embodiments, the warhead is of formula: (i-11). In certain embodiments, the warhead is of formula: (i-12). In certain embodiments, the warhead is of formula: (i-13). In certain embodiments, the warhead is of formula: (i-14). In certain embodiments, the warhead is of formula: (i-43). In certain embodiments, the warhead is of formula (i-15). In certain embodiments, the warhead is of formula: (i-16). In certain embodiments, the warhead is of formula: (i-17). In certain embodiments, the warhead is of formula: (i-18). In certain embodiments, the warhead is of formula (i-19). In certain embodiments, the warhead is of formula: (i-20). In certain embodiments, the warhead is (i- 21). In certain embodiments, the warhead is of formula: (i-22). In certain embodiments, the warhead is of formula: (i-23). In certain embodiments, the warhead is of formula: (i-26). In certain embodiments, the warhead is of formula: (i-27). In certain embodiments, the warhead is of formula: (i-28). In certain embodiments, the warhead is of formula (i- 29). In certain embodiments, the warhead is of formula: (i-30). In certain embodiments, the warhead is of formula: (i-31). In certain embodiments, the warhead is of formula : (i-34). In certain embodiments, the warhead is of formula: (i-35). In certain embodiments, the warhead is of formula: . In certain embodiments, the warhead is of formula: (i-37). In certain embodiments, D 1 is a warhead is of formula: . In certain embodiments, the warhead is of formula: (i-38). In certain embodiments, the warhead is of formula: (i-39). In certain embodiments, the warhead is of formula: (i-40). In certain embodiments, the warhead is of formula: (i-42). In certain embodiments, the warhead is of formula: (i-2). In certain embodiments, the warhead is of formula (i-3). In certain embodiments, the warhead is of formula: (i-4). In certain embodiments, the warhead is of formula: (i-5). In certain embodiments, the warhead is of formula: (i-6). In certain embodiments, the warhead is of formula: (i-7). In certain embodiments, the warhead is of formula: (i-8). In certain embodiments, the warhead is of formula: (i-9). In certain embodiments, the warhead is of formula: (i-10). In certain embodiments, the warhead is (i-11). In certain embodiments, the warhead is of formula: (i-12). In certain embodiments, the warhead is of formula: (i-13). In certain embodiments, the warhead is of formula: ( 1 i-14). In certain embodiments, D is a warhead is of formula: (i-14) (e.g., ). In cert 1 ain embodiments, D is a warhead is of formula: . In certain embodiments, the warhead is of formula: (i-15). [00144] In certain embodiments, the warhead is of formula: (i-16). In certain embodiments, the warhead is of formula: (i-17). In certain embodiments, the warhead is of formula: (i-18). In certain embodiments, the warhead is of formula: (i-19). In certain embodiments, the warhead is of formula: (i-20). In certain embodiments, the warhead is of formula: (i-21). In certain embodiments, the warhead is of formula: (i-22). In certain embodiments, the warhead is of formula: (i-23). In certain embodiments, the warhead is of formula: (i-26). In certain embodiments, the warhead is of formula: (i-27). In certain embodiments, the warhead is of formula: (i-28). In certain embodiments, the warhead is of formula: (i-29). [00145] In certain embodiments, the warhead is of formula: (i-30). In certain embodiments, the warhead is of formula: (i-31). In certain embodiments, the warhead is of formula: (i-34). In certain embodiments, the warhead is of formula: (i-35). In certain embodiments, the warhead is of formula: (i-36). In certain embodiments, D 1 is a warhead is of formula: (i-36) (e.g., ). In certain embodiments, D 1 is a warhead is of formula: . In certain embodiments, the warhead is of formula: (i-37). In certain embodiments, D 1 is a warhead is of formula: . In certain embodiments, the warhead is of formula (i-38). In certain embodiments, the warhead is of formula: (i-39). In certain embodiments, the warhead is of formula: (i-40). In certain embodiments, the warhead is of formula: (i-42). In certain embodiments, the warhead is of formula: (i-43). [00146] In certain embodiments, L 3 is a bond (e.g., a single bond, a double bond, or a triple bond). In certain embodiments, L 3 is a single bond. In certain embodiments, L 3 is a double bond. In certain embodiments, L 3 is a triple bond. In certain embodiments, L 3 is an optionally substituted C 1–4 hydrocarbon chain, optionally wherein one or more carbon units of the hydrocarbon chain are independently replaced with –C=O–, –O–, –S–, –NR L3a –, – NR L3a C(=O)–, –C(=O)NR L3a –, –SC(=O)–, –C(=O)S–, –OC(=O)–, –C(=O)O–, – NR L3a C(=S)–, –C(=S)NR L3a –, trans–CR L3b =CR L3b –, cis–CR L3b =CR L3b –, –C≡C–, –S(=O)–, – S(=O)O–, –OS(=O)–, –S(=O)NR L3a –, –NR L3a S(=O)–, –S(=O) 2 –, –S(=O) 2 O–, –OS(=O) 2 –, – S(=O) 2 NR L3a –, or –NR L3a S(=O) 2 –, wherein R L3a is hydrogen, substituted or unsubstituted C 1 – 6 alkyl, or a nitrogen protecting group, and wherein each occurrence of R L3b is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or two R L3b groups are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring. In certain embodiments, L 4 is a bond (e.g., a single bond, a double bond, or a triple bond). In certain embodiments, L 4 is an optionally substituted branched C 1–6 hydrocarbon chain (e.g., i- Pr). In certain embodiments, L 4 is an optionally substituted unbranched C 1–6 hydrocarbon chain (e.g., n-Pr, or n-Bu). In certain embodiments, at least one instance of R E1 is H. In certain embodiments, at least one instance of R E1 is halogen (e.g., F, Cl, Br, or I). In certain embodiments, at least one instance of R E1 is optionally substituted alkyl (e.g., Me, or Et). In certain embodiments, at least one instance of R E1 is optionally substituted alkenyl (e.g., optionally substituted vinyl). In certain embodiments, at least one instance of R E1 is optionally substituted alkynyl. In certain embodiments, at least one instance of R E1 is substituted or unsubstituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, at least one instance of R E1 is substituted or unsubstituted heterocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic heterocyclyl comprising zero, one, or two double bonds in the heterocyclic ring system, wherein one, two, or three atoms in the heterocyclic ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, at least one instance of R E1 is substituted or unsubstituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, at least one instance of R E1 is substituted or unsubstituted phenyl. In certain embodiments, at least one instance of R E1 is substituted or unsubstituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, at least one instance of R E1 is –CN. In certain embodiments, at least one instance of R E1 is –CH 2 OR EE , wherein each instance of R EE is independently hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl. In certain embodiments, at least one instance of R E1 is –CH 2 N(R EF ) 2 or –N(R EF ) 2 , wherein each instance of R EF is independently hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, optionally wherein two R EF groups are joined to form an optionally substituted heterocyclic ring. In certain embodiments, at least one instance of R E1 is – CH 2 SR EE or –SR EE (e.g., –CH 2 SMe or –SMe). In certain embodiments, at least one instance of R E1 is –OR EE (e.g., –OMe). In certain embodiments, at least one instance of R E1 is – Si(R EG )3, wherein each instance of R EG is independently hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl (e.g., –Si(Me) 3 ). [00147] In certain embodiments, at least one instance of R E2 is H. In certain embodiments, at least one instance of R E2 is halogen (e.g., F, Cl, Br, or I). In certain embodiments, at least one instance of R E2 is optionally substituted alkyl (e.g., Me, or Et). In certain embodiments, at least one instance of R E2 is optionally substituted alkenyl (e.g., optionally substituted vinyl). In certain embodiments, at least one instance of R E2 is optionally substituted alkynyl. In certain embodiments, at least one instance of R E2 is substituted or unsubstituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, at least one instance of R E2 is substituted or unsubstituted heterocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic heterocyclyl comprising zero, one, or two double bonds in the heterocyclic ring system, wherein one, two, or three atoms in the heterocyclic ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, at least one instance of R E2 is substituted or unsubstituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, at least one instance of R E2 is substituted or unsubstituted phenyl. In certain embodiments, at least one instance of R E2 is substituted or unsubstituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6- membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, at least one instance of R E2 is –CN. In certain embodiments, at least one instance of R E2 is – CH 2 OR EE , wherein each instance of R EE is independently hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl. In certain embodiments, at least one instance of R E2 is –CH 2 N(R EF ) 2 or N(R EF ) 2 , wherein each instance of R EF is independently hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, optionally wherein two R EF groups are joined to form an optionally substituted heterocyclic ring. In certain embodiments, at least one instance of R E2 is –CH 2 SR EE or –SR EE (e.g., – CH 2 SMe or –SMe). In certain embodiments, at least one instance of R E2 is –OR EE (e.g., – OMe). In certain embodiments, at least one instance of R E2 is –Si(R EG )3, wherein each instance of R EG is independently hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl (e.g., –Si(Me)3). In certain embodiments, at least one instance of R E3 is H. In certain embodiments, at least one instance of R E3 is halogen (e.g., F, Cl, Br, or I). In certain embodiments, at least one instance of R E3 is optionally substituted alkyl (e.g., Me, or Et). In certain embodiments, at least one instance of R E3 is optionally substituted alkenyl (e.g., optionally substituted vinyl). In certain embodiments, at least one instance of R E3 is optionally substituted alkynyl. In certain embodiments, at least one instance of R E3 is substituted or unsubstituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, at least one instance of R E3 is substituted or unsubstituted heterocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic heterocyclyl comprising zero, one, or two double bonds in the heterocyclic ring system, wherein one, two, or three atoms in the heterocyclic ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, at least one instance of R E3 is substituted or unsubstituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, at least one instance of R E3 is substituted or unsubstituted phenyl. In certain embodiments, at least one instance of R E3 is substituted or unsubstituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, at least one instance of R E3 is –CN. In certain embodiments, at least one instance of R E3 is –CH 2 OR EE , wherein each instance of R EE is independently hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl. In certain embodiments, at least one instance of R E3 is –CH 2 N(R EF ) 2 or –N(R EF ) 2 , wherein each instance of R EF is independently hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, optionally wherein two R EF groups are joined to form an optionally substituted heterocyclic ring. In certain embodiments, at least one instance of R E3 is – CH 2 SR EE or –SR EE (e.g., –CH 2 SMe or –SMe). In certain embodiments, at least one instance of R E3 is –OR EE (e.g., –OMe). In certain embodiments, at least one instance of R E3 is – Si(R EG )3, wherein each instance of R EG is independently hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl (e.g., –Si(Me)3). In certain embodiments, R E1 and R E3 are joined to form an optionally substituted carbocyclic ring (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R E1 and R E3 are joined to form an optionally substituted heterocyclic ring (e.g., substituted or unsubstituted, 3- to 7- membered, monocyclic heterocyclyl comprising zero, one, or two double bonds in the heterocyclic ring system, wherein one, two, or three atoms in the heterocyclic ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R E2 and R E3 are joined to form an optionally substituted carbocyclic ring (e.g., substituted or unsubstituted, 3- to 7- membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R E2 and R E3 are joined to form an optionally substituted heterocyclic ring (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic heterocyclyl comprising zero, one, or two double bonds in the heterocyclic ring system, wherein one, two, or three atoms in the heterocyclic ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R E1 and R E2 are joined to form an optionally substituted carbocyclic ring (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R E1 and R E2 are joined to form an optionally substituted heterocyclic ring (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic heterocyclyl comprising zero, one, or two double bonds in the heterocyclic ring system, wherein one, two, or three atoms in the heterocyclic ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R E4 is a leaving group (e.g., halogen, or a sulfonic acid ester, e.g., –O(tosylate) or –O(mesylate)). In certain embodiments, R E5 is halogen (e.g., F, Cl, Br, or I). In certain embodiments, R E6 is H. In certain embodiments, R E6 is substituted or unsubstituted C 1-6 alkyl (e.g., Me, is –CF3, Bn, Et, perfluoroethyl, Pr, perfluoropropyl, Bu, or perfluorobutyl). In certain embodiments, R E6 is a nitrogen protecting group (e.g., Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts). In certain embodiments, at least one instance of Y is O. In certain embodiments, at least one instance of Y is S. In certain embodiments, at least one instance of Y is NR E7 , wherein R E7 is hydrogen, substituted or unsubstituted C 1–6 alkyl, or a nitrogen protecting group (e.g., NMe). In certain embodiments, a is 1. In certain embodiments, a is 2. In certain embodiments, at least one instance of z is 0. In certain embodiments, at least one instance of z is 1. In certain embodiments, at least one instance of z is 2. In certain embodiments, at least one instance of z is 3. In certain embodiments, at least one instance of z is 4. In certain embodiments, at least one instance of z is 5. In certain embodiments, at least one instance of z is 6. [00148] In certain embodiments, D 1 is a warhead of formula: (i-1), (i-37) 1 . In certain embodiments, D is a warhead of formula: (i-1), (i-14), or (i-36). In cert 1 ain embodiments, D is a warhead of formula: , , , , In certain embodiments, D 1 is a warhead of formula: , , , or . In certain embodiments, D 1 is a warhead of formula: [00149] In certain embodiments, the compound of Formula (I) is of the Formula (I-i): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00150] In certain embodiments, the compound of Formula (I-i) is of the formula: or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00151] In certain embodiments, the compound of Formula (I) is of the Formula (I-j): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00152] In certain embodiments, the compound of Formula (I-j) is of the formula: , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00153] In certain embodiments, the compound of Formula (I) is of the Formula (I-k): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00154] In certain embodiments, the compound of Formula (I-k) is of the formula: or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00155] In certain embodiments, the compound of Formula (I) is of the Formula (I-l): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00156] In certain embodiments, the compound of Formula (I-l) is of the formula: or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00157] In certain embodiments, the compound of Formula (I) is of the Formula (I-m): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00158] In certain embodiments, the compound of Formula (I-m) is of the formula: or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00159] In certain embodiments, the compound of Formula (I-m) is of the formula: , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00160] In certain embodiments, the compound of Formula (I-m) is of the formula: or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00161] In certain embodiments, the compound of Formula (I) is of the Formula (I-n): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00162] In certain embodiments, the compound of Formula (I-n) is of the formula: or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00163] In certain embodiments, the compound of Formula (I-n) is of the formula: , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00164] In certain embodiments, the compound of Formula (I-n) is of the formula: , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00165] In certain embodiments, the compound of Formula (I) is of the Formula (I-o): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00166] In certain embodiments, the compound of Formula (I-o) is of the formula: , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00167] In certain embodiments, the compound of Formula (I-o) is of the formula: , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00168] In certain embodiments, the compound of Formula (I-o) is of the formula: , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00169] In certain embodiments, the compound of Formula (I) is of the Formula (I-p): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00170] In certain embodiments, the compound of Formula (I-p) is of the formula: or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00171] In certain embodiments, the compound of Formula (I-p) is of the formula: or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00172] In certain embodiments, the compound of Formula (I-p) is of the formula: or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00173] In certain embodiments, the compound of Formula (II) is of the Formula (II-c): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00174] In certain embodiments, the compound of Formula (II-c) is of the formula: , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00175] In certain embodiments, the compound of Formula (II-c) is of the formula: , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00176] In certain embodiments, the compound of Formula (II-c) is of the formula: , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00177] In certain embodiments, the compound of Formula (II) is of the Formula (II-d): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00178] In certain embodiments, the compound of Formula (II-d) is of the formula: , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00179] In certain embodiments, the compound of Formula (II-d) is of the formula: , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00180] In certain embodiments, the compound of Formula (II-d) is of the formula: , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00181] In certain embodiments, the compound of Formula (II) is of the Formula (II-e): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00182] In certain embodiments, the compound of Formula (II-e) is of the formula: , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00183] In certain embodiments, the compound of Formula (II-e) is of the formula: , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00184] In certain embodiments, the compound of Formula (II-e) is of the formula: , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00185] In certain embodiments, the compound of Formula (I’) is of the formula: , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof. [00186] In certain embodiments, the compound of Formula (I’’), Formula (I’), Formula (I), Formula (II’), or Formula (II), is a compound provided in any one of the Examples below. [00187] In certain embodiments, a compound described herein is a compound of Formula (I’’), Formula (I’), Formula (I), Formula (II’), or Formula (II), or a pharmaceutically acceptable salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, isotopically enriched derivative, or prodrug thereof. In certain embodiments, a compound described herein is a compound of Formula (I’’), Formula (I’), Formula (I), Formula (II’), or Formula (II), or a pharmaceutically acceptable salt thereof. In certain embodiments, a compound described herein is a compound of Formula (I), or a pharmaceutically acceptable salt thereof. In certain embodiments, a compound described herein is a compound of Formula (I’’), or a pharmaceutically acceptable salt thereof. In certain embodiments, a compound described herein is a compound of Formula (I’), or a pharmaceutically acceptable salt thereof. In certain embodiments, a compound described herein is a compound of Formula (II’), or a pharmaceutically acceptable salt thereof. In certain embodiments, a compound described herein is a compound of Formula (II), or a pharmaceutically acceptable salt thereof. [00188] Certain compounds described herein bind, covalently modify, and/or inhibit a transcription factor. In certain embodiments, the compounds described herein irreversibly inhibit a transcription factor. In certain embodiments, the compounds described herein reversibly inhibit a transcription factor. In certain embodiments, the transcription factor is TEAD. In certain embodiments, the transcription factor is TEAD1. In certain embodiments, the transcription factor is TEAD2. In certain embodiments, the transcription factor is TEAD3. In certain embodiments, the transcription factor is TEAD4. In certain embodiments, the compounds described herein covalently bind to the transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). In certain embodiments, the compounds described herein reversibly bind to the transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). In certain embodiments, the compounds described herein non-reversibly bind to the transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). In certain embodiments, the compounds described herein modulate the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). In certain embodiments, the compounds described herein inhibit a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). In certain embodiments, the compounds described herein inhibit the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). In certain embodiments, the compounds described herein reversibly inhibit the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). [00189] The binding affinity of a compound described herein to a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) may be measured by the dissociation constant (Kd) value of an adduct of the compound and the TEAD using methods known in the art (e.g., isothermal titration calorimetry (ITC)). In certain embodiments, the Kd value of the adduct is not more than about 100 µM, not more than about 10 µM, not more than about 1 µM, not more than about 100 nM, not more than about 10 nM, or not more than about 1 nM. [00190] In certain embodiments, the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) is inhibited by a compound described herein. The inhibition of the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) by a compound described herein may be measured by determining the half maximal inhibitory concentration (IC 50 ) of the compound when the compound, or a pharmaceutical composition thereof, is contacted with the transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). The IC 5 0 values may be obtained using methods known in the art (e.g., by a competition binding assay). In certain embodiments, the IC 50 value of a compound described herein is not more than about 1 mM, not more than about 100 µM, not more than about 10 µM, not more than about 1 µM, not more than about 100 nM, not more than about 10 nM, or not more than about 1 nM. [00191] The compounds described herein may selectively modulate the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). In certain embodiments, the compounds selectively inhibit a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). In certain embodiments, the compounds selectively inhibit the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). In certain embodiments, the compounds inhibit the activity of two or more transcription factors (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) to the same extent. [00192] The selectivity of a compound described herein in inhibiting the activity of a first transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) over a second transcription factor different from the first transcription factor (e.g., a different TEAD) may be measured by the quotient of the IC 50 value of the compound in inhibiting the activity of the second transcription factor different from the first transcription factor (e.g., a different TEAD) over the IC 5 0 value of the compound in inhibiting the activity of the first transcription factor (e.g., TEAD). The selectivity of a compound described herein in modulating the activity of a first transcription factor (e.g., TEAD) over a second transcription factor different from the first transcription factor (e.g., a different TEAD) may also be measured by the quotient of the K d value of an adduct of the compound and the second transcription factor different from the first transcription factor (e.g., a different TEAD) over the K d value of an adduct of the compound and the first transcription factor different from the first transcription factor (e.g., a different TEAD). In certain embodiments, the selectivity is at least about 1- fold, at least about 3-fold, at least about 10-fold, at least about 30-fold, at least about 100- fold, at least about 300-fold, at least about 1,000-fold, at least about 3,000-fold, at least about 10,000-fold, at least about 30,000-fold, or at least about 100,000-fold. In certain embodiments, the selectivity is at least about 2-fold, about 5-fold, about 10-fold, or more. [00193] It is expected that the compounds described herein may be useful in treating and/or preventing diseases associated with aberrant activity (e.g., increased activity, undesired activity, abnormal activity) of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). It is known in the art that transcription factors are implicated in a wide range of diseases and conditions, such as proliferative diseases, inflammatory diseases, and autoimmune diseases. Therefore, the compounds described herein are expected to be useful in treating and/or preventing diseases (e.g., proliferative diseases, inflammatory diseases, autoimmune diseases). [00194] In certain embodiments, a compound of Formula (I’’) is of the formula:
, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, composition, or mixture thereof. [00195] In certain embodiments, the compound of Formula (I’’) is of the formula:
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, composition, or mixture thereof. [00196] In certain embodiments, the compound of Formula (I’’) is of the formula: or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, composition, or mixture thereof. [00197] In certain embodiments, the compound of Formula (II’) is of the formula: or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, composition, or mixture thereof. Pharmaceutical Compositions, Kits, and Administration [00198] The present disclosure also provides pharmaceutical compositions comprising a compound described herein and optionally a pharmaceutically acceptable excipient. In certain embodiments, a compound described herein is a compound of Formula (I’’), Formula (I’), Formula (I), Formula (II’), or Formula (II), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. [00199] In certain embodiments, the compound described herein is provided in an effective amount in the pharmaceutical composition. In certain embodiments, the effective amount is a therapeutically effective amount. In certain embodiments, the effective amount is a prophylactically effective amount. In certain embodiments, a therapeutically effective amount is an amount effective for inhibiting the aberrant activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). In certain embodiments, a therapeutically effective amount is an amount effective for treating a disease (e.g., a disease associated with aberrant activity of a transcription factor (e.g., TEAD (e.g., proliferative diseases, inflammatory diseases, autoimmune diseases)). In certain embodiments, a therapeutically effective amount is an amount effective for inhibiting the aberrant activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) and treating a disease (e.g., a disease associated with aberrant activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) (e.g., proliferative disease, inflammatory disease, autoimmune disease))). In certain embodiments, a therapeutically effective amount is an amount effective for inhibiting the transcription of a gene (e.g., a gene controlled or regulated by a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4)) in a subject and/or biological sample. In certain embodiments, a prophylactically effective amount is an amount effective for inhibiting the aberrant activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). In certain embodiments, a prophylactically effective amount is an amount effective for preventing or keeping a subject in need thereof in remission of a disease (e.g., a disease associated with aberrant activity of a transcription factor (e.g., TEAD) (e.g., proliferative disease, inflammatory disease, autoimmune disease)). In certain embodiments, a prophylactically effective amount is an amount effective for inhibiting the aberrant activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4), and preventing or keeping a subject in need thereof in remission of a disease (e.g., a disease associated with aberrant activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) (e.g., proliferative disease, inflammatory disease, autoimmune disease)). In certain embodiments, a prophylactically effective amount is an amount effective for inhibiting the transcription of a gene (e.g., a gene controlled or regulated by a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4)) in a subject and/or biological sample. [00200] In certain embodiments, the effective amount is an amount effective for inhibiting the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98%. In certain embodiments, the effective amount is an amount effective for inhibiting the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) by not more than 10%, not more than 20%, not more than 30%, not more than 40%, not more than 50%, not more than 60%, not more than 70%, not more than 80%, not more than 90%, not more than 95%, or not more than 98%. In certain embodiments, the effective amount is an amount effective for increasing the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98%. In certain embodiments, the effective amount is an amount effective for increasing the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) by not more than 10%, not more than 20%, not more than 30%, not more than 40%, not more than 50%, not more than 60%, not more than 70%, not more than 80%, not more than 90%, not more than 95%, or not more than 98%. [00201] In certain embodiments, the subject is an animal. The animal may be of either sex and may be at any stage of development. In certain embodiments, the subject described herein is a human. In certain embodiments, the subject is a non-human animal. In certain embodiments, the subject is a mammal. In certain embodiments, the subject is a non-human mammal. In certain embodiments, the subject is a domesticated animal, such as a dog, cat, cow, pig, horse, sheep, or goat. In certain embodiments, the subject is a companion animal, such as a dog or cat. In certain embodiments, the subject is a livestock animal, such as a cow, pig, horse, sheep, or goat. In certain embodiments, the subject is a zoo animal. In another embodiment, the subject is a research animal, such as a rodent (e.g., mouse, rat), dog, pig, or non-human primate. In certain embodiments, the animal is a genetically engineered animal. In certain embodiments, the animal is a transgenic animal (e.g., transgenic mice and transgenic pigs). In certain embodiments, the subject is a fish or reptile. [00202] In certain embodiments, the cell being contacted with a compound or pharmaceutical composition thereof described herein is in vitro. In certain embodiments, the cell being contacted with a compound or pharmaceutical composition thereof described herein is in vivo. [00203] Pharmaceutical compositions described herein can be prepared by any method known in the art of pharmacology. In general, such preparatory methods include bringing the compound described herein (i.e., the “active ingredient”) into association with a carrier or excipient, and/or one or more other accessory ingredients, and then, if necessary and/or desirable, shaping, and/or packaging the product into a desired single- or multi-dose unit. [00204] Pharmaceutical compositions can be prepared, packaged, and/or sold in bulk, as a single unit dose, and/or as a plurality of single unit doses. A “unit dose” is a discrete amount of the pharmaceutical composition comprising a predetermined amount of the active ingredient. The amount of the active ingredient is generally equal to the dosage of the active ingredient which would be administered to a subject and/or a convenient fraction of such a dosage, such as one-half or one-third of such a dosage. [00205] Relative amounts of the active ingredient, the pharmaceutically acceptable excipient, and/or any additional ingredients in a pharmaceutical composition described herein will vary, depending upon the identity, size, and/or condition of the subject treated and further depending upon the route by which the composition is to be administered. The composition may comprise between 0.1% and 100% (w/w) active ingredient. [00206] Pharmaceutically acceptable excipients used in the manufacture of provided pharmaceutical compositions include inert diluents, dispersing and/or granulating agents, surface active agents and/or emulsifiers, disintegrating agents, binding agents, preservatives, buffering agents, lubricating agents, and/or oils. Excipients such as cocoa butter and suppository waxes, coloring agents, coating agents, sweetening, flavoring, and perfuming agents may also be present in the composition. [00207] Exemplary diluents include calcium carbonate, sodium carbonate, calcium phosphate, dicalcium phosphate, calcium sulfate, calcium hydrogen phosphate, sodium phosphate lactose, sucrose, cellulose, microcrystalline cellulose, kaolin, mannitol, sorbitol, inositol, sodium chloride, dry starch, cornstarch, powdered sugar, and mixtures thereof. [00208] Exemplary granulating and/or dispersing agents include potato starch, corn starch, tapioca starch, sodium starch glycolate, clays, alginic acid, guar gum, citrus pulp, agar, bentonite, cellulose, and wood products, natural sponge, cation-exchange resins, calcium carbonate, silicates, sodium carbonate, cross-linked poly(vinyl-pyrrolidone) (crospovidone), sodium carboxymethyl starch (sodium starch glycolate), carboxymethyl cellulose, cross- linked sodium carboxymethyl cellulose (croscarmellose), methylcellulose, pregelatinized starch (starch 1500), microcrystalline starch, water insoluble starch, calcium carboxymethyl cellulose, magnesium aluminum silicate (Veegum), sodium lauryl sulfate, quaternary ammonium compounds, and mixtures thereof. [00209] Exemplary surface active agents and/or emulsifiers include natural emulsifiers (e.g., acacia, agar, alginic acid, sodium alginate, tragacanth, chondrux, cholesterol, xanthan, pectin, gelatin, egg yolk, casein, wool fat, cholesterol, wax, and lecithin), colloidal clays (e.g., bentonite (aluminum silicate) and Veegum (magnesium aluminum silicate)), long chain amino acid derivatives, high molecular weight alcohols (e.g., stearyl alcohol, cetyl alcohol, oleyl alcohol, triacetin monostearate, ethylene glycol distearate, glyceryl monostearate, and propylene glycol monostearate, polyvinyl alcohol), carbomers (e.g., carboxy polymethylene, polyacrylic acid, acrylic acid polymer, and carboxyvinyl polymer), carrageenan, cellulosic derivatives (e.g., carboxymethylcellulose sodium, powdered cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose), sorbitan fatty acid esters (e.g., polyoxyethylene sorbitan monolaurate (Tween ® 20), polyoxyethylene sorbitan (Tween ® 60), polyoxyethylene sorbitan monooleate (Tween ® 80), sorbitan monopalmitate (Span ® 40), sorbitan monostearate (Span ® 60), sorbitan tristearate (Span ® 65), glyceryl monooleate, sorbitan monooleate (Span ® 80), polyoxyethylene esters (e.g., polyoxyethylene monostearate (Myrj ® 45), polyoxyethylene hydrogenated castor oil, polyethoxylated castor oil, polyoxymethylene stearate, and Solutol ® ), sucrose fatty acid esters, polyethylene glycol fatty acid esters (e.g., Cremophor ® ), polyoxyethylene ethers, (e.g., polyoxyethylene lauryl ether (Brij ® 30)), poly(vinyl-pyrrolidone), diethylene glycol monolaurate, triethanolamine oleate, sodium oleate, potassium oleate, ethyl oleate, oleic acid, ethyl laurate, sodium lauryl sulfate, Pluronic ® F-68, poloxamer P-188, cetrimonium bromide, cetylpyridinium chloride, benzalkonium chloride, docusate sodium, and/or mixtures thereof. [00210] Exemplary binding agents include starch (e.g., cornstarch and starch paste), gelatin, sugars (e.g., sucrose, glucose, dextrose, dextrin, molasses, lactose, lactitol, mannitol, etc.), natural and synthetic gums (e.g., acacia, sodium alginate, extract of Irish moss, panwar gum, ghatti gum, mucilage of isapol husks, carboxymethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, microcrystalline cellulose, cellulose acetate, poly(vinyl-pyrrolidone), magnesium aluminum silicate (Veegum ® ), and larch arabogalactan), alginates, polyethylene oxide, polyethylene glycol, inorganic calcium salts, silicic acid, polymethacrylates, waxes, water, alcohol, and/or mixtures thereof. [00211] Exemplary preservatives include antioxidants, chelating agents, antimicrobial preservatives, antifungal preservatives, antiprotozoan preservatives, alcohol preservatives, acidic preservatives, and other preservatives. In certain embodiments, the preservative is an antioxidant. In other embodiments, the preservative is a chelating agent. [00212] Exemplary antioxidants include alpha tocopherol, ascorbic acid, acorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, monothioglycerol, potassium metabisulfite, propionic acid, propyl gallate, sodium ascorbate, sodium bisulfite, sodium metabisulfite, and sodium sulfite. [00213] Exemplary chelating agents include ethylenediaminetetraacetic acid (EDTA) and salts and hydrates thereof (e.g., sodium edetate, disodium edetate, trisodium edetate, calcium disodium edetate, dipotassium edetate, and the like), citric acid and salts and hydrates thereof (e.g., citric acid monohydrate), fumaric acid and salts and hydrates thereof, malic acid and salts and hydrates thereof, phosphoric acid and salts and hydrates thereof, and tartaric acid and salts and hydrates thereof. Exemplary antimicrobial preservatives include benzalkonium chloride, benzethonium chloride, benzyl alcohol, bronopol, cetrimide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, chloroxylenol, cresol, ethyl alcohol, glycerin, hexetidine, imidurea, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric nitrate, propylene glycol, and thimerosal. [00214] Exemplary antifungal preservatives include butyl paraben, methyl paraben, ethyl paraben, propyl paraben, benzoic acid, hydroxybenzoic acid, potassium benzoate, potassium sorbate, sodium benzoate, sodium propionate, and sorbic acid. [00215] Exemplary alcohol preservatives include ethanol, polyethylene glycol, phenol, phenolic compounds, bisphenol, chlorobutanol, hydroxybenzoate, and phenylethyl alcohol. [00216] Exemplary acidic preservatives include vitamin A, vitamin C, vitamin E, beta- carotene, citric acid, acetic acid, dehydroacetic acid, ascorbic acid, sorbic acid, and phytic acid. [00217] Other preservatives include tocopherol, tocopherol acetate, deteroxime mesylate, cetrimide, butylated hydroxyanisol (BHA), butylated hydroxytoluened (BHT), ethylenediamine, sodium lauryl sulfate (SLS), sodium lauryl ether sulfate (SLES), sodium bisulfite, sodium metabisulfite, potassium sulfite, potassium metabisulfite, Glydant ® Plus, Phenonip ® , methylparaben, Germall ® 115, Germaben ® II, Neolone ® , Kathon ® , and Euxyl ® . [00218] Exemplary buffering agents include citrate buffer solutions, acetate buffer solutions, phosphate buffer solutions, ammonium chloride, calcium carbonate, calcium chloride, calcium citrate, calcium glubionate, calcium gluceptate, calcium gluconate, D- gluconic acid, calcium glycerophosphate, calcium lactate, propanoic acid, calcium levulinate, pentanoic acid, dibasic calcium phosphate, phosphoric acid, tribasic calcium phosphate, calcium hydroxide phosphate, potassium acetate, potassium chloride, potassium gluconate, potassium mixtures, dibasic potassium phosphate, monobasic potassium phosphate, potassium phosphate mixtures, sodium acetate, sodium bicarbonate, sodium chloride, sodium citrate, sodium lactate, dibasic sodium phosphate, monobasic sodium phosphate, sodium phosphate mixtures, tromethamine, magnesium hydroxide, aluminum hydroxide, alginic acid, pyrogen-free water, isotonic saline, Ringer’s solution, ethyl alcohol, and mixtures thereof. [00219] Exemplary lubricating agents include magnesium stearate, calcium stearate, stearic acid, silica, talc, malt, glyceryl behanate, hydrogenated vegetable oils, polyethylene glycol, sodium benzoate, sodium acetate, sodium chloride, leucine, magnesium lauryl sulfate, sodium lauryl sulfate, and mixtures thereof. [00220] Exemplary natural oils include almond, apricot kernel, avocado, babassu, bergamot, black current seed, borage, cade, camomile, canola, caraway, carnauba, castor, cinnamon, cocoa butter, coconut, cod liver, coffee, corn, cotton seed, emu, eucalyptus, evening primrose, fish, flaxseed, geraniol, gourd, grape seed, hazel nut, hyssop, isopropyl myristate, jojoba, kukui nut, lavandin, lavender, lemon, litsea cubeba, macademia nut, mallow, mango seed, meadowfoam seed, mink, nutmeg, olive, orange, orange roughy, palm, palm kernel, peach kernel, peanut, poppy seed, pumpkin seed, rapeseed, rice bran, rosemary, safflower, sandalwood, sasquana, savoury, sea buckthorn, sesame, shea butter, silicone, soybean, sunflower, tea tree, thistle, tsubaki, vetiver, walnut, and wheat germ oils. Exemplary synthetic oils include, but are not limited to, butyl stearate, caprylic triglyceride, capric triglyceride, cyclomethicone, diethyl sebacate, dimethicone 360, isopropyl myristate, mineral oil, octyldodecanol, oleyl alcohol, silicone oil, and mixtures thereof. [00221] Liquid dosage forms for oral and parenteral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active ingredients, the liquid dosage forms may comprise inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (e.g., cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. In certain embodiments for parenteral administration, the conjugates described herein are mixed with solubilizing agents such as Cremophor ® , alcohols, oils, modified oils, glycols, polysorbates, cyclodextrins, polymers, and mixtures thereof. [00222] Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions can be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation can be a sterile injectable solution, suspension, or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that can be employed are water, Ringer’s solution, U.S.P., and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or di-glycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables. [00223] The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use. [00224] In order to prolong the effect of a drug, it is often desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This can be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution, which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form may be accomplished by dissolving or suspending the drug in an oil vehicle. [00225] Compositions for rectal or vaginal administration are typically suppositories which can be prepared by mixing the conjugates described herein with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol, or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active ingredient. [00226] Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active ingredient is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or (a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, (b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, (c) humectants such as glycerol, (d) disintegrating agents such as agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, (e) solution retarding agents such as paraffin, (f) absorption accelerators such as quaternary ammonium compounds, (g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, (h) absorbents such as kaolin and bentonite clay, and (i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets, and pills, the dosage form may include a buffering agent. [00227] Solid compositions of a similar type can be employed as fillers in soft and hard- filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. The solid dosage forms of tablets, dragées, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the art of pharmacology. They may optionally comprise opacifying agents and can be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of encapsulating compositions which can be used include polymeric substances and waxes. Solid compositions of a similar type can be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. [00228] The active ingredient can be in a micro-encapsulated form with one or more excipients as noted above. The solid dosage forms of tablets, dragées, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings, and other coatings well known in the pharmaceutical formulating art. In such solid dosage forms the active ingredient can be admixed with at least one inert diluent such as sucrose, lactose, or starch. Such dosage forms may comprise, as is normal practice, additional substances other than inert diluents, e.g., tableting lubricants and other tableting aids such a magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms may comprise buffering agents. They may optionally comprise opacifying agents and can be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of encapsulating agents which can be used include polymeric substances and waxes. [00229] Dosage forms for topical and/or transdermal administration of a compound described herein may include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants, and/or patches. Generally, the active ingredient is admixed under sterile conditions with a pharmaceutically acceptable carrier or excipient and/or any needed preservatives and/or buffers as can be required. Additionally, the present disclosure contemplates the use of transdermal patches, which often have the added advantage of providing controlled delivery of an active ingredient to the body. Such dosage forms can be prepared, for example, by dissolving and/or dispensing the active ingredient in the proper medium. Alternatively or additionally, the rate can be controlled by either providing a rate controlling membrane and/or by dispersing the active ingredient in a polymer matrix and/or gel. [00230] Suitable devices for use in delivering intradermal pharmaceutical compositions described herein include short needle devices. Intradermal compositions can be administered by devices which limit the effective penetration length of a needle into the skin. Alternatively or additionally, conventional syringes can be used in the classical mantoux method of intradermal administration. Jet injection devices which deliver liquid formulations to the dermis via a liquid jet injector and/or via a needle which pierces the stratum corneum and produces a jet which reaches the dermis are suitable. Ballistic powder/particle delivery devices which use compressed gas to accelerate the compound in powder form through the outer layers of the skin to the dermis are suitable. [00231] Formulations suitable for topical administration include, but are not limited to, liquid and/or semi-liquid preparations such as liniments, lotions, oil-in-water and/or water-in- oil emulsions such as creams, ointments, and/or pastes, and/or solutions and/or suspensions. Topically administrable formulations may, for example, comprise from about 1% to about 10% (w/w) active ingredient, although the concentration of the active ingredient can be as high as the solubility limit of the active ingredient in the solvent. Formulations for topical administration may further comprise one or more of the additional ingredients described herein. [00232] A pharmaceutical composition described herein can be prepared, packaged, and/or sold in a formulation suitable for pulmonary administration via the buccal cavity. Such a formulation may comprise dry particles which comprise the active ingredient and which have a diameter in the range from about 0.5 to about 7 nanometers, or from about 1 to about 6 nanometers. Such compositions are conveniently in the form of dry powders for administration using a device comprising a dry powder reservoir to which a stream of propellant can be directed to disperse the powder and/or using a self-propelling solvent/powder dispensing container such as a device comprising the active ingredient dissolved and/or suspended in a low-boiling propellant in a sealed container. Such powders comprise particles wherein at least 98% of the particles by weight have a diameter greater than 0.5 nanometers and at least 95% of the particles by number have a diameter less than 7 nanometers. Alternatively, at least 95% of the particles by weight have a diameter greater than 1 nanometer and at least 90% of the particles by number have a diameter less than 6 nanometers. Dry powder compositions may include a solid fine powder diluent such as sugar and are conveniently provided in a unit dose form. [00233] Low boiling propellants generally include liquid propellants having a boiling point of below 65 °F at atmospheric pressure. Generally the propellant may constitute 50 to 99.9% (w/w) of the composition, and the active ingredient may constitute 0.1 to 20% (w/w) of the composition. The propellant may further comprise additional ingredients such as a liquid non-ionic and/or solid anionic surfactant and/or a solid diluent (which may have a particle size of the same order as particles comprising the active ingredient). [00234] Pharmaceutical compositions described herein formulated for pulmonary delivery may provide the active ingredient in the form of droplets of a solution and/or suspension. Such formulations can be prepared, packaged, and/or sold as aqueous and/or dilute alcoholic solutions and/or suspensions, optionally sterile, comprising the active ingredient, and may conveniently be administered using any nebulization and/or atomization device. Such formulations may further comprise one or more additional ingredients including, but not limited to, a flavoring agent such as saccharin sodium, a volatile oil, a buffering agent, a surface active agent, and/or a preservative such as methylhydroxybenzoate. The droplets provided by this route of administration may have an average diameter in the range from about 0.1 to about 200 nanometers. [00235] Formulations described herein as being useful for pulmonary delivery are useful for intranasal delivery of a pharmaceutical composition described herein. Another formulation suitable for intranasal administration is a coarse powder comprising the active ingredient and having an average particle from about 0.2 to 500 micrometers. Such a formulation is administered by rapid inhalation through the nasal passage from a container of the powder held close to the nares. [00236] Formulations for nasal administration may, for example, comprise from about as little as 0.1% (w/w) to as much as 100% (w/w) of the active ingredient, and may comprise one or more of the additional ingredients described herein. A pharmaceutical composition described herein can be prepared, packaged, and/or sold in a formulation for buccal administration. Such formulations may, for example, be in the form of tablets and/or lozenges made using conventional methods, and may contain, for example, 0.1 to 20% (w/w) active ingredient, the balance comprising an orally dissolvable and/or degradable composition and, optionally, one or more of the additional ingredients described herein. Alternately, formulations for buccal administration may comprise a powder and/or an aerosolized and/or atomized solution and/or suspension comprising the active ingredient. Such powdered, aerosolized, and/or aerosolized formulations, when dispersed, may have an average particle and/or droplet size in the range from about 0.1 to about 200 nanometers, and may further comprise one or more of the additional ingredients described herein. [00237] A pharmaceutical composition described herein can be prepared, packaged, and/or sold in a formulation for ophthalmic administration. Such formulations may, for example, be in the form of eye drops including, for example, a 0.1-1.0% (w/w) solution and/or suspension of the active ingredient in an aqueous or oily liquid carrier or excipient. Such drops may further comprise buffering agents, salts, and/or one or more other of the additional ingredients described herein. Other ophthalmically-administrable formulations which are useful include those which comprise the active ingredient in microcrystalline form and/or in a liposomal preparation. Ear drops and/or eye drops are also contemplated as being within the scope of this disclosure. [00238] Although the descriptions of pharmaceutical compositions provided herein are principally directed to pharmaceutical compositions which are suitable for administration to humans, it will be understood by the skilled artisan that such compositions are generally suitable for administration to animals of all sorts. Modification of pharmaceutical compositions suitable for administration to humans in order to render the compositions suitable for administration to various animals is well understood, and the ordinarily skilled veterinary pharmacologist can design and/or perform such modification with ordinary experimentation. [00239] Compounds provided herein are typically formulated in dosage unit form for ease of administration and uniformity of dosage. It will be understood, however, that the total daily usage of the compositions described herein will be decided by a physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular subject or organism will depend upon a variety of factors including the disease being treated and the severity of the disorder; the activity of the specific active ingredient employed; the specific composition employed; the age, body weight, general health, sex, and diet of the subject; the time of administration, route of administration, and rate of excretion of the specific active ingredient employed; the duration of the treatment; drugs used in combination or coincidental with the specific active ingredient employed; and like factors well known in the medical arts. [00240] The compounds and compositions provided herein can be administered by any route, including enteral (e.g., oral), parenteral, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, subcutaneous, intraventricular, transdermal, interdermal, rectal, intravaginal, intraperitoneal, topical (as by powders, ointments, creams, and/or drops), mucosal, nasal, bucal, sublingual; by intratracheal instillation, bronchial instillation, and/or inhalation; and/or as an oral spray, nasal spray, and/or aerosol. Specifically contemplated routes are oral administration, intravenous administration (e.g., systemic intravenous injection), regional administration via blood and/or lymph supply, and/or direct administration to an affected site. In general, the most appropriate route of administration will depend upon a variety of factors including the nature of the agent (e.g., its stability in the environment of the gastrointestinal tract), and/or the condition of the subject (e.g., whether the subject is able to tolerate oral administration). In certain embodiments, the compound or pharmaceutical composition described herein is suitable for topical administration to the eye of a subject. [00241] The exact amount of a compound required to achieve an effective amount will vary from subject to subject, depending, for example, on species, age, and general condition of a subject, severity of the side effects or disorder, identity of the particular compound, mode of administration, and the like. An effective amount may be included in a single dose (e.g., single oral dose) or multiple doses (e.g., multiple oral doses). In certain embodiments, when multiple doses are administered to a subject or applied to a biological sample (e.g., tissue, cell), any two doses of the multiple doses include different or substantially the same amounts of a compound described herein. In certain embodiments, when multiple doses are administered to a subject or applied to a biological sample (e.g., tissue, cell), the frequency of administering the multiple doses to the subject or applying the multiple doses to the biological sample (e.g., tissue, cell) is three doses a day, two doses a day, one dose a day, one dose every other day, one dose every third day, one dose every week, one dose every two weeks, one dose every three weeks, or one dose every four weeks. In certain embodiments, the frequency of administering the multiple doses to the subject or applying the multiple doses to the biological sample (e.g., tissue, cell) is one dose per day. In certain embodiments, the frequency of administering the multiple doses to the subject or applying the multiple doses to the biological sample (e.g., tissue, cell) is two doses per day. In certain embodiments, the frequency of administering the multiple doses to the subject or applying the multiple doses to the biological sample (e.g., tissue, cell) is three doses per day. In certain embodiments, when multiple doses are administered to a subject or applied to a biological sample (e.g., tissue, cell), the duration between the first dose and last dose of the multiple doses is one day, two days, four days, one week, two weeks, three weeks, one month, two months, three months, four months, six months, nine months, one year, two years, three years, four years, five years, seven years, ten years, fifteen years, twenty years, or the lifetime of the subject, tissue, or cell. In certain embodiments, the duration between the first dose and last dose of the multiple doses is three months, six months, or one year. In certain embodiments, the duration between the first dose and last dose of the multiple doses is the lifetime of the subject, tissue, or cell. In certain embodiments, a dose (e.g., a single dose, or any dose of multiple doses) described herein includes independently between 0.1 µg and 1 µg, between 0.001 mg and 0.01 mg, between 0.01 mg and 0.1 mg, between 0.1 mg and 1 mg, between 1 mg and 3 mg, between 3 mg and 10 mg, between 10 mg and 30 mg, between 30 mg and 100 mg, between 100 mg and 300 mg, between 300 mg and 1,000 mg, or between 1 g and 10 g, inclusive, of a compound described herein. In certain embodiments, a dose described herein includes independently between 1 mg and 3 mg, inclusive, of a compound described herein. In certain embodiments, a dose described herein includes independently between 3 mg and 10 mg, inclusive, of a compound described herein. In certain embodiments, a dose described herein includes independently between 10 mg and 30 mg, inclusive, of a compound described herein. In certain embodiments, a dose described herein includes independently between 30 mg and 100 mg, inclusive, of a compound described herein. [00242] Dose ranges as described herein provide guidance for the administration of provided pharmaceutical compositions to an adult. The amount to be administered to, for example, a child or an adolescent can be determined by a medical practitioner or person skilled in the art and can be lower or the same as that administered to an adult. [00243] A compound or pharmaceutical composition thereof, as described herein, can be administered in combination with one or more additional pharmaceutical agents (e.g., therapeutically and/or prophylactically active agents). The compounds or compositions can be administered in combination with additional pharmaceutical agents that improve their activity (e.g., activity (e.g., potency and/or efficacy) in treating a disease in a subject in need thereof, in preventing a disease in a subject in need thereof, in inhibiting the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4)) in a subject and/or biological sample (e.g., tissue, cell)), improve bioavailability, improve safety, reduce drug resistance, reduce and/or modify metabolism, inhibit excretion, and/or modify distribution in a subject and/or biological sample (e.g., tissue, cell). It will also be appreciated that the therapy employed may achieve a desired effect for the same disorder, and/or it may achieve different effects. In certain embodiments, a pharmaceutical composition described herein including a compound described herein and an additional pharmaceutical agent shows a synergistic effect that is absent in a pharmaceutical composition including one of the compounds described herein and the additional pharmaceutical agent, but not both. [00244] The compound or pharmaceutical composition thereof can be administered concurrently with, prior to, or subsequent to one or more additional pharmaceutical agents, which may be useful as, e.g., combination therapies. Pharmaceutical agents include therapeutically active agents. Pharmaceutical agents also include prophylactically active agents. Pharmaceutical agents include small organic molecules such as drug compounds (e.g., compounds approved for human or veterinary use by the U.S. Food and Drug Administration as provided in the Code of Federal Regulations (CFR)), peptides, proteins, carbohydrates, monosaccharides, oligosaccharides, polysaccharides, nucleoproteins, mucoproteins, lipoproteins, synthetic polypeptides or proteins, small molecules linked to proteins, glycoproteins, steroids, nucleic acids, DNAs, RNAs, nucleotides, nucleosides, oligonucleotides, antisense oligonucleotides, lipids, hormones, vitamins, and cells. In certain embodiments, the additional pharmaceutical agent is a pharmaceutical agent useful for treating and/or preventing a disease (e.g., proliferative disease, inflammatory disease, autoimmune disease). Each additional pharmaceutical agent may be administered at a dose and/or on a time schedule determined for that pharmaceutical agent. The additional pharmaceutical agents may also be administered together with each other and/or with the compound or pharmaceutical composition thereof described herein in a single dose or administered separately in different doses. The particular combination to employ in a regimen will take into account compatibility of the compound described herein with the additional pharmaceutical agent(s) and/or the desired therapeutic and/or prophylactic effect to be achieved. In general, it is expected that the additional pharmaceutical agent(s) in combination be utilized at levels that do not exceed the levels at which they are utilized individually. In some embodiments, the levels utilized in combination will be lower than those utilized individually. [00245] The additional pharmaceutical agents include, but are not limited to, anti- proliferative agents, anti-cancer agents, anti-angiogenesis agents, anti-inflammatory agents, immunosuppressants, anti-bacterial agents, anti-viral agents, cardiovascular agents, cholesterol-lowering agents, anti-diabetic agents, anti-allergic agents, contraceptive agents, pain-relieving agents, and a combination thereof. In certain embodiments, the additional pharmaceutical agent is an anti-proliferative agent (e.g., anti-cancer agent). In certain embodiments, the additional pharmaceutical agent is ABITREXATE (methotrexate), ADE, Adriamycin RDF (doxorubicin hydrochloride), Ambochlorin (chlorambucil), ARRANON (nelarabine), ARZERRA (ofatumumab), BOSULIF (bosutinib), BUSULFEX (busulfan), CAMPATH (alemtuzumab), CERUBIDINE (daunorubicin hydrochloride), CLAFEN (cyclophosphamide), CLOFAREX (clofarabine), CLOLAR (clofarabine), CVP, CYTOSAR- U (cytarabine), CYTOXAN (cyclophosphamide), ERWINAZE (Asparaginase Erwinia Chrysanthemi), FLUDARA (fludarabine phosphate), FOLEX (methotrexate), FOLEX PFS (methotrexate), GAZYVA (obinutuzumab), GLEEVEC (imatinib mesylate), Hyper-CVAD, ICLUSIG (ponatinib hydrochloride), IMBRUVICA (ibrutinib), LEUKERAN (chlorambucil), LINFOLIZIN (chlorambucil), MARQIBO (vincristine sulfate liposome), METHOTREXATE LPF (methorexate), MEXATE (methotrexate), MEXATE-AQ (methotrexate), mitoxantrone hydrochloride, MUSTARGEN (mechlorethamine hydrochloride), MYLERAN (busulfan), NEOSAR (cyclophosphamide), ONCASPAR (Pegaspargase), PURINETHOL (mercaptopurine), PURIXAN (mercaptopurine), Rubidomycin (daunorubicin hydrochloride), SPRYCEL (dasatinib), SYNRIBO (omacetaxine mepesuccinate), TARABINE PFS (cytarabine), TASIGNA (nilotinib), TREANDA (bendamustine hydrochloride), TRISENOX (arsenic trioxide), VINCASAR PFS (vincristine sulfate), ZYDELIG (idelalisib), or a combination thereof. In certain embodiments, the additional pharmaceutical agent is an anti- lymphoma agent. In certain embodiments, the additional pharmaceutical agent is ABITREXATE (methotrexate), ABVD, ABVE, ABVE-PC, ADCETRIS (brentuximab vedotin), ADRIAMYCIN PFS (doxorubicin hydrochloride), ADRIAMYCIN RDF (doxorubicin hydrochloride), AMBOCHLORIN (chlorambucil), AMBOCLORIN (chlorambucil), ARRANON (nelarabine), BEACOPP, BECENUM (carmustine), BELEODAQ (belinostat), BEXXAR (tositumomab and iodine I 131 tositumomab), BICNU (carmustine), BLENOXANE (bleomycin), CARMUBRIS (carmustine), CHOP, CLAFEN (cyclophosphamide), COPP, COPP-ABV, CVP, CYTOXAN (cyclophosphamide), DEPOCYT (liposomal cytarabine), DTIC-DOME (dacarbazine), EPOCH, FOLEX (methotrexate), FOLEX PFS (methotrexate), FOLOTYN (pralatrexate), HYPER-CVAD, ICE, IMBRUVICA (ibrutinib), INTRON A (recombinant interferon alfa-2b), ISTODAX (romidepsin), LEUKERAN (chlorambucil), LINFOLIZIN (chlorambucil), Lomustine, MATULANE (procarbazine hydrochloride), METHOTREXATE LPF (methotrexate), MEXATE (methotrexate), MEXATE-AQ (methotrexate), MOPP, MOZOBIL (plerixafor), MUSTARGEN (mechlorethamine hydrochloride), NEOSAR (cyclophosphamide), OEPA, ONTAK (denileukin diftitox), OPPA, R-CHOP, REVLIMID (lenalidomide), RITUXAN (rituximab), STANFORD V, TREANDA (bendamustine hydrochloride), VAMP, VELBAN (vinblastine sulfate), VELCADE (bortezomib), VELSAR (vinblastine sulfate), VINCASAR PFS (vincristine sulfate), ZEVALIN (ibritumomab tiuxetan), ZOLINZA (vorinostat), ZYDELIG (idelalisib), or a combination thereof. In certain embodiments, the additional pharmaceutical agent is REVLIMID (lenalidomide), DACOGEN (decitabine), VIDAZA (azacitidine ), CYTOSAR-U (cytarabine), IDAMYCIN (idarubicin ), CERUBIDINE (daunorubicin), LEUKERAN (chlorambucil), NEOSAR (cyclophosphamide), FLUDARA (fludarabine), LEUSTATIN (cladribine), or a combination thereof. In certain embodiments, the additional pharmaceutical agent is ABITREXATE (methotrexate), ABRAXANE (paclitaxel albumin-stabilized nanoparticle formulation), AC, AC-T, ADE, ADRIAMYCIN PFS (doxorubicin hydrochloride), ADRUCIL (fluorouracil), AFINITOR (everolimus), AFINITOR DISPERZ (everolimus), ALDARA (imiquimod), ALIMTA (pemetrexed disodium), AREDIA (pamidronate disodium), ARIMIDEX (anastrozole), AROMASIN (exemestane), AVASTIN (bevacizumab), BECENUM (carmustine), BEP, BICNU (carmustine), BLENOXANE (bleomycin), CAF, CAMPTOSAR (irinotecan hydrochloride), CAPOX, CAPRELSA (vandetanib), CARBOPLATIN-TAXOL, CARMUBRIS (carmustine), CASODEX (bicalutamide), CEENU (lomustine), CERUBIDINE (daunorubicin hydrochloride), CERVARIX (recombinant HPV bivalent vaccine), CLAFEN (cyclophosphamide), CMF, COMETRIQ (cabozantinib-s-malate), COSMEGEN (dactinomycin), CYFOS (ifosfamide), CYRAMZA (ramucirumab), CYTOSAR-U (cytarabine), CYTOXAN (cyclophosphamide), DACOGEN (decitabine), DEGARELIX, DOXIL (doxorubicin hydrochloride liposome), DOXORUBICIN HYDROCHLORIDE, DOX-SL (doxorubicin hydrochloride liposome), DTIC-DOME (dacarbazine), EFUDEX (fluorouracil), ELLENCE (epirubicin hydrochloride), ELOXATIN (oxaliplatin), ERBITUX (cetuximab), ERIVEDGE (vismodegib), ETOPOPHOS (etoposide phosphate), EVACET (doxorubicin hydrochloride liposome), FARESTON (toremifene), FASLODEX (fulvestrant), FEC, FEMARA (letrozole), FLUOROPLEX (fluorouracil), FOLEX (methotrexate), FOLEX PFS (methotrexate), FOLFIRI , FOLFIRI-BEVACIZUMAB, FOLFIRI-CETUXIMAB, FOLFIRINOX, FOLFOX, FU-LV, GARDASIL (recombinant human papillomavirus (HPV) quadrivalent vaccine), GEMCITABINE-CISPLATIN, GEMCITABINE-OXALIPLATIN, GEMZAR (gemcitabine hydrochloride), GILOTRIF (afatinib dimaleate), GLEEVEC (imatinib mesylate), GLIADEL (carmustine implant), GLIADEL WAFER (carmustine implant), HERCEPTIN (trastuzumab), HYCAMTIN (topotecan hydrochloride), IFEX (ifosfamide), IFOSFAMIDUM (ifosfamide), INLYTA (axitinib), INTRON A (recombinant interferon alfa-2b), IRESSA (gefitinib), IXEMPRA (ixabepilone), JAKAFI (ruxolitinib phosphate), JEVTANA (cabazitaxel), KADCYLA (ado-trastuzumab emtansine), KEYTRUDA (pembrolizumab), KYPROLIS (carfilzomib), LIPODOX (doxorubicin hydrochloride liposome), LUPRON (leuprolide acetate), LUPRON DEPOT (leuprolide acetate), LUPRON DEPOT-3 MONTH (leuprolide acetate), LUPRON DEPOT-4 MONTH (leuprolide acetate), LUPRON DEPOT-PED (leuprolide acetate), MEGACE (megestrol acetate), MEKINIST (trametinib), METHAZOLASTONE (temozolomide), METHOTREXATE LPF (methotrexate), MEXATE (methotrexate), MEXATE-AQ (methotrexate), MITOXANTRONE HYDROCHLORIDE, MITOZYTREX (mitomycin c), MOZOBIL (plerixafor), MUSTARGEN (mechlorethamine hydrochloride), MUTAMYCIN (mitomycin c), MYLOSAR (azacitidine), NAVELBINE (vinorelbine tartrate), NEOSAR (cyclophosphamide), NEXAVAR (sorafenib tosylate), NOLVADEX (tamoxifen citrate), NOVALDEX (tamoxifen citrate), OFF, PAD, PARAPLAT (carboplatin), PARAPLATIN (carboplatin), PEG-INTRON (peginterferon alfa-2b), PEMETREXED DISODIUM, PERJETA (pertuzumab), PLATINOL (cisplatin), PLATINOL-AQ (cisplatin), POMALYST (pomalidomide), prednisone, PROLEUKIN (aldesleukin), PROLIA (denosumab), PROVENGE (sipuleucel-t), REVLIMID (lenalidomide), RUBIDOMYCIN (daunorubicin hydrochloride), SPRYCEL (dasatinib), STIVARGA (regorafenib), SUTENT (sunitinib malate), SYLATRON (peginterferon alfa-2b), SYLVANT (siltuximab), SYNOVIR (thalidomide), TAC, TAFINLAR (dabrafenib), TARABINE PFS (cytarabine), TARCEVA (erlotinib hydrochloride), TASIGNA (nilotinib), TAXOL (paclitaxel), TAXOTERE (docetaxel), TEMODAR (temozolomide), THALOMID (thalidomide), TOPOSAR (etoposide), TORISEL (temsirolimus), TPF, TRISENOX (arsenic trioxide), TYKERB (lapatinib ditosylate), VECTIBIX (panitumumab), VEIP, VELBAN (vinblastine sulfate), VELCADE (bortezomib), VELSAR (vinblastine sulfate), VEPESID (etoposide), VIADUR (leuprolide acetate), VIDAZA (azacitidine), VINCASAR PFS (vincristine sulfate), VOTRIENT (pazopanib hydrochloride), WELLCOVORIN (leucovorin calcium), XALKORI (crizotinib), XELODA (capecitabine), XELOX, XGEVA (denosumab), XOFIGO (radium 223 dichloride), XTANDI (enzalutamide), YERVOY (ipilimumab), ZALTRAP (ziv- aflibercept), ZELBORAF (vemurafenib), ZOLADEX (goserelin acetate), ZOMETA (zoledronic acid), ZYKADIA (ceritinib), ZYTIGA (abiraterone acetate), ENMD-2076, PCI- 32765, AC 2 20, dovitinib lactate (TKI258, CHIR-258), BIBW 2992 (TOVOK TM ), SGX523, PF-04217903, PF-02341066, PF-299804, BMS-777607, ABT-869, MP470, BIBF 1120 (VARGATEF®), AP24534, JNJ-26483327, MGCD265, DCC-2036, BMS-690154, CEP- 11981, tivozanib (AV-951), OSI-930, MM-121, XL-184, XL-647, and/or XL228), proteasome inhibitors (e.g., bortezomib (Velcade)), mTOR inhibitors (e.g., rapamycin, temsirolimus (CCI-779), everolimus (RAD-001), ridaforolimus, AP23573 (Ariad), AZD8055 (AstraZeneca), BEZ235 (Novartis), BGT226 (Norvartis), XL765 (Sanofi Aventis), PF- 4691502 (Pfizer), GDC0980 (Genentech), SF1126 (Semafoe) and OSI-027 (OSI)), oblimersen, gemcitabine, carminomycin, leucovorin, pemetrexed, cyclophosphamide, dacarbazine, procarbizine, prednisolone, dexamethasone, campathecin, plicamycin, asparaginase, aminopterin, methopterin, porfiromycin, melphalan, leurosidine, leurosine, chlorambucil, trabectedin, procarbazine, discodermolide, carminomycin, aminopterin, and hexamethyl melamine, or a combination thereof. In certain embodiments, the additional pharmaceutical agent is ibrutinib. In certain embodiments, the additional pharmaceutical agent is a transcription factor inhibitor (e.g., inhibitor of EGFR and/or MEK). In certain embodiments, the additional pharmaceutical agent is an inhibitor of a gene and/or protein in the Hippo signaling pathway. In certain embodiments, the additional pharmaceutical agent is an inhibitor of EGFR (e.g., osimertinib, gefitinib) and/or an inhibitor of MEK (e.g., trametinib, selumetinib). In certain embodiments, the additional pharmaceutical agent is an inhibitor of EGFR (e.g., osimertinib, gefitinib). In certain embodiments, the additional pharmaceutical agent comprises an inhibitor of MEK (e.g., trametinib, selumetinib). In certain embodiments, the additional pharmaceutical agent comprises an inhibitor of tankyrase inhibitor and/or an indirect inhibitor of YAP (e.g., compound XAV939). In certain embodiments, the additional pharmaceutical agent is an anti-proliferative agent (e.g., anti- cancer agent, such as an inhibitor of EGFR, an inhibitor of MEK, or an inhibitor of EGFR and an inhibitor of MEK). In certain embodiments, the additional pharmaceutical agent is a transcription factor inhibitor (e.g., inhibitor of EGFR and/or MEK). In certain embodiments, the additional pharmaceutical agent is an agent for treating lung cancer (e.g., non-small cell lung cancer (NSCLC)). In certain embodiments, the additional pharmaceutical agent is an agent for treating lung cancer (e.g., non-small cell lung cancer (NSCLC)), such as NSCLC with a mutation in a gene and/or protein in the Hippo signaling pathway (e.g., mutation in EGFR). In certain embodiments, the additional pharmaceutical agent is a kinase inhibitor. In certain embodiments, the additional pharmaceutical agent is a tyrosine kinase inhibitor (TKI). In certain embodiments, the additional pharmaceutical agent is an agent for treating a cancer that has a mutation in a gene of the Hippo signaling pathway. In certain embodiments, the additional pharmaceutical agent is an agent for treating a cancer that has a mutation in EGFR. In certain embodiments, the additional pharmaceutical agent is an agent for treating a cancer that has a mutation in MEK. In certain embodiments, the additional pharmaceutical agent is an agent for treating a cancer that is an EGFR-mutant non-small cell lung cancer. In certain embodiments, the additional pharmaceutical agent is an agent for treating a cancer that is resistant to certain anti-proliferative agents (e.g., cancers resistant to inhibitors of EGFR, such as osimertinib, and/or inhibitors of MEK, such as trametinib). In certain embodiments, the additional pharmaceutical agent is an agent for treating a cancer that is resistant to inhibitors of EGFR and/or MEK. In certain embodiments, the additional pharmaceutical agent is an agent for treating a cancer that is resistant to osimertinib and trametinib. In certain embodiments, the additional pharmaceutical agent is an agent for treating a cancer that is resistant to tyrosine kinase inhibitors (TKI’s). [00246] In certain embodiments, the additional pharmaceutical agent is a binder or inhibitor of TEAD (e.g., TEAD1, TEAD2, TEAD3, TEAD4)). In certain embodiments, the additional pharmaceutical agent is a binder or inhibitor of TEAD. In certain embodiments, the additional pharmaceutical agent is a binder or inhibitor of TEAD1. In certain embodiments, the additional pharmaceutical agent is a binder or inhibitor of TEAD2. In certain embodiments, the additional pharmaceutical agent is a binder or inhibitor of TEAD3. In certain embodiments, the additional pharmaceutical agent is a binder or inhibitor of TEAD4. In certain embodiments, the additional pharmaceutical agent is a binder or inhibitor of Bruton’s tyrosine kinase (BTK). In certain embodiments, the additional pharmaceutical agent is selected from the group consisting of epigenetic and transcriptional modulators (e.g., DNA methyltransferase inhibitors, histone deacetylase inhibitors (HDAC inhibitors), lysine methyltransferase inhibitors), antimitotic drugs (e.g., taxanes and vinca alkaloids), hormone receptor modulators (e.g., estrogen receptor modulators and androgen receptor modulators), cell signaling pathway inhibitors (e.g., tyrosine protein kinase inhibitors), modulators of protein stability (e.g., proteasome inhibitors), Hsp90 inhibitors, glucocorticoids, all-trans retinoic acids, and other agents that promote differentiation. In certain embodiments, the compounds described herein or pharmaceutical compositions can be administered in combination with an anti-cancer therapy including, but not limited to, surgery, radiation therapy, transplantation (e.g., stem cell transplantation, bone marrow transplantation), immunotherapy, and chemotherapy. [00247] Also encompassed by the disclosure are kits (e.g., pharmaceutical packs). The kits provided may comprise a pharmaceutical composition or compound described herein and a container (e.g., a vial, ampule, bottle, syringe, and/or dispenser package, or other suitable container). In some embodiments, provided kits may optionally further include a second container comprising a pharmaceutical excipient for dilution or suspension of a pharmaceutical composition or compound described herein. In some embodiments, the pharmaceutical composition or compound described herein provided in the first container and the second container are combined to form one unit dosage form. [00248] Thus, in one aspect, provided are kits including a first container comprising a compound or pharmaceutical composition described herein. In certain embodiments, the kits are useful for treating a disease (e.g., proliferative disease, inflammatory disease, autoimmune disease) in a subject in need thereof. In certain embodiments, the kits are useful for preventing a disease (e.g., proliferative disease, inflammatory disease, autoimmune disease) in a subject in need thereof. In certain embodiments, the kits are useful for inhibiting the activity (e.g., aberrant or unwanted activity, such as increased activity) of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) in a subject and/or biological sample (e.g., tissue, cell). In certain embodiments, the kits are useful for inhibiting the transcription of a gene (e.g., a gene controlled or regulated by a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4)) in a subject and/or biological sample. [00249] In certain embodiments, a kit described herein further includes instructions for using the compound or pharmaceutical composition included in the kit. A kit described herein may also include information as required by a regulatory agency such as the U.S. Food and Drug Administration (FDA). In certain embodiments, the information included in the kits is prescribing information. In certain embodiments, the kits and instructions provide for treating a disease (e.g., proliferative disease, inflammatory disease, autoimmune disease) in a subject in need thereof. In certain embodiments, the kits and instructions provide for preventing a disease (e.g., proliferative disease, inflammatory disease, autoimmune disease) in a subject in need thereof. In certain embodiments, the kits and instructions provide for modulating (e.g., inhibiting) the activity (e.g., aberrant activity, such as increased activity) of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) in a subject and/or biological sample (e.g., tissue, cell). In certain embodiments, the kits and instructions provide for inhibiting the transcription of a gene (e.g., a gene controlled or regulated by a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4)) in a subject and/or biological sample. A kit described herein may include one or more additional pharmaceutical agents described herein as a separate composition. Methods of Treatment and Uses [00250] The present disclosure provides methods of modulating (e.g., inhibiting or increasing) the activity (e.g., aberrant activity, such as increased or decreased activity) of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) using compounds described herein, which may be optionally administered in combination with an additional pharmaceutical agent, for example, modulators of other transcription factors (e.g., YAP, EGFR, MEK). The present disclosure provides methods of modulating (e.g., inhibiting or increasing) the activity (e.g., aberrant activity, such as increased or decreased activity) of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) in a subject and/or biological sample (e.g., tissue, cell), using compounds described herein, which may be optionally administered in combination with an additional pharmaceutical agent, for example, modulators of other transcription factors (e.g., YAP, EGFR, MEK). The present disclosure also provides methods for the treatment of a wide range of diseases, such as diseases associated with the aberrant activity (e.g., increased activity) of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4), using compounds described herein, which may be optionally administered in combination with an additional pharmaceutical agent, for example, modulators of other transcription factors (e.g., YAP, EGFR, MEK), for example, for treating proliferative diseases, inflammatory diseases, and/or autoimmune diseases in a subject in need thereof. The present disclosure provides methods for the treatment and/or prevention of a proliferative disease (e.g., cancers (e.g., carcinoma, sarcoma); lung cancer, breast cancer, liver cancer, pancreatic cancer, gastric cancer, ovarian cancer, colon cancer, colorectal cancer, skin cancer, esophageal cancer)), inflammatory disease (e.g., fibrosis), or autoimmune disease (e.g., sclerosis), using compounds described herein, which may be optionally administered in combination with an additional pharmaceutical agent, for example, modulators of other transcription factors (e.g., YAP, EGFR, MEK). The present disclosure provides methods for inhibiting the transcription of a gene (e.g., a gene controlled or regulated by a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4)) in a subject and/or biological sample (e.g., tissue, cell), using compounds described herein, which may be optionally administered in combination with an additional pharmaceutical agent, for example, modulators of other transcription factors (e.g., YAP, EGFR, MEK). [00251] The present disclosure also provides a compound of Formula (I’’), Formula (I’), Formula (I), Formula (II’), or Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, or pharmaceutical composition thereof, which may be optionally administered in combination with an additional pharmaceutical agent, for example, modulators of other transcription factors (e.g., YAP, EGFR, MEK), for use in the treatment of diseases, such as proliferative diseases, inflammatory diseases, and autoimmune diseases, in a subject in need thereof. [00252] The present disclosure also provides uses of a compound of Formula (I’’), Formula (I’), Formula (I), Formula (II’), or Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, or pharmaceutical composition thereof, which may be optionally administered in combination with an additional pharmaceutical agent, for example, modulators of other transcription factors (e.g., YAP, EGFR, MEK), in the manufacture of a medicament for the treatment of various diseases, such as proliferative diseases, inflammatory diseases, and autoimmune diseases, in a subject in need thereof. [00253] In another aspect, the present disclosure provides methods of modulating the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) in a subject and/or biological sample (e.g., cell, tissue) using compounds described herein, which may be optionally administered in combination with an additional pharmaceutical agent, for example, modulators of other transcription factors (e.g., YAP, EGFR, MEK). In certain embodiments, provided are methods of inhibiting the activity of a transcription factor (e.g., TEAD) in a subject. In certain embodiments, provided are methods of inhibiting the activity of a transcription factor (e.g., TEAD) in a cell. In certain embodiments, provided are methods of increasing the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) in a subject. The compounds described herein may exhibit transcription factor inhibitory activity; the ability to inhibit TEAD; the ability to inhibit TEAD1, without inhibiting another transcription factor (e.g., a different TEAD); the ability to inhibit TEAD2, without inhibiting another transcription factor (e.g., a different TEAD); the ability to inhibit TEAD3, without inhibiting another transcription factor (e.g., a different TEAD); the ability to inhibit TEAD4, without inhibiting another transcription factor (e.g., a different TEAD); a therapeutic effect and/or preventative effect in the treatment of cancers; a therapeutic effect and/or preventative effect in the treatment of proliferative diseases, inflammatory diseases, and/or autoimmune diseases; and/or a therapeutic profile (e.g., optimum safety and curative effect) that is superior to existing chemotherapeutic agents, or agents for treating inflammatory diseases and/or autoimmune diseases. [00254] In certain embodiments, provided are methods of decreasing the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) in a subject or biological sample (e.g., cell, tissue) by a method described herein by at least about 1%, at least about 3%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90%. In certain embodiments, the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) in a subject or biological sample (e.g., cell, tissue) is decreased by a method described herein by at least about 1%, at least about 3%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90%. In some embodiments, the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) in a subject or biological sample (e.g., cell, tissue) is selectively inhibited by the compound. In some embodiments, the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) in a subject or biological sample (e.g., cell, tissue) is selectively decreased by the compound. [00255] Without wishing to be bound by any particular theory, the compounds described herein are able to bind (e.g., covalently modify) the transcription factor being inhibited. In certain embodiments, a compound described herein is able to bind (e.g., covalently modify) the transcription factor. In certain embodiments, the compound described herein is able to covalently bind a cysteine residue of the transcription factor. In certain embodiments, the compound described herein is able to covalently bind a cysteine residue of TEAD. In certain embodiments, the compound described herein is able to covalently bind a cysteine residue of TEAD1. In certain embodiments, the compound is capable of covalently binding cysteine 359 of TEAD1. In certain embodiments, the compound described herein is able to covalently bind a cysteine residue of TEAD2. In certain embodiments, the compound is capable of covalently binding cysteine 380 of TEAD2. In certain embodiments, the compound is capable of covalently binding TEAD1. In certain embodiments, the compound is capable of covalently binding TEAD2. In certain embodiments, the compound is capable of covalently binding TEAD3. In certain embodiments, the compound described herein is able to covalently bind a cysteine residue of TEAD4. In certain embodiments, the compound is capable of covalently binding TEAD4. In certain embodiments, the compound is capable of binding the YAP/TAZ domain of a TEAD family transcription factor. In certain embodiments, the compound is capable of covalently modifying TEAD1 (e.g., C 3 59 of TEAD1). In certain embodiments, the compound is capable of covalently modifying TEAD2 (e.g., C 3 80 of TEAD2). In certain embodiments, the compound is capable of covalently modifying C 3 59 (cysteine 359) of TEAD1. In certain embodiments, the compound is capable of covalently modifying C 3 80 (cysteine 380) of TEAD2. In certain embodiments, the compound is capable of covalently modifying TEAD3. In certain embodiments, the compound is capable of covalently modifying TEAD4. In certain embodiments, the compound is capable of covalently modifying TEAD1. In certain embodiments, the compound is capable of covalently modifying TEAD2. In certain embodiments, the compound is capable of covalently modifying TEAD3. In certain embodiments, the compound is capable of covalently modifying TEAD4. In certain embodiments, the compound is capable of non-covalently inhibiting TEAD1. In certain embodiments, the compound is capable of non-covalently inhibiting TEAD2. In certain embodiments, the compound is capable of non-covalently inhibiting TEAD3. In certain embodiments, the compound is capable of non-covalently inhibiting TEAD4. [00256] In another aspect, the present disclosure provides methods of inhibiting a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) in a subject, the methods comprising administering to the subject an effective amount (e.g., therapeutically effective amount) of a compound, or pharmaceutical composition thereof, as described herein. In another aspect, the present disclosure provides methods of inhibiting the activity of a transcription factor (e.g., TEAD, such asTEAD1, TEAD2, TEAD3, TEAD4) in a subject, the methods comprising administering to the subject an effective amount (e.g., therapeutically effective amount) of a compound, or pharmaceutical composition thereof, as described herein. In another aspect, the present disclosure provides methods of inhibiting the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) in a biological sample, the methods comprising contacting the biological sample with an effective amount of a compound, or pharmaceutical composition thereof, as described herein. In another aspect, the present disclosure provides methods of inhibiting the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) in a biological sample (e.g., tissue, cell), the methods comprising contacting the biological sample (e.g., tissue, cell) with an effective amount of a compound, or pharmaceutical composition thereof, as described herein. [00257] In another aspect, the present disclosure provides methods of inhibiting the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) in a cell, the methods comprising contacting the cell with an effective amount of a compound, or pharmaceutical composition thereof, as described herein. [00258] In another aspect, the present disclosure provides methods of inhibiting the transcription of a gene (e.g., a gene controlled or regulated by a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4)) in a subject, the methods comprising administering to the subject an effective amount (e.g., therapeutically effective amount) of a compound, or pharmaceutical composition thereof, as described herein. In another aspect, the present disclosure provides methods of inhibiting the transcription of a gene (e.g., a gene controlled or regulated by a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4)) in a subject, the methods comprising administering to the subject an effective amount (e.g., therapeutically effective amount) of a compound, or pharmaceutical composition thereof, as described herein. In another aspect, the present disclosure provides methods of inhibiting the transcription of a gene (e.g., a gene controlled or regulated by a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4)) in a biological sample, the methods comprising contacting the biological sample with an effective amount of a compound, or pharmaceutical composition thereof, as described herein. In another aspect, the present disclosure provides methods of inhibiting the transcription of a gene (e.g., a gene controlled or regulated by a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4)) in a biological sample (e.g., tissue, cell), the methods comprising contacting the biological sample (e.g., tissue, cell) with an effective amount of a compound, or pharmaceutical composition thereof, as described herein. In another aspect, the present disclosure provides methods of inhibiting the transcription of a gene (e.g., a gene controlled or regulated by a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4)) in a cell, the methods comprising contacting the cell with an effective amount of a compound, or pharmaceutical composition thereof, as described herein. [00259] In certain embodiments, the subject being treated is a mammal. In certain embodiments, the subject is a human. In certain embodiments, the subject is a domesticated animal, such as a dog, cat, cow, pig, horse, sheep, or goat. In certain embodiments, the subject is a companion animal, such as a dog or cat. In certain embodiments, the subject is a livestock animal, such as a cow, pig, horse, sheep, or goat. In certain embodiments, the subject is a zoo animal. In another embodiment, the subject is a research animal such as a rodent, dog, or non-human primate. In certain embodiments, the subject is a non-human transgenic animal, such as a transgenic mouse or transgenic pig. [00260] In certain embodiments, the biological sample being contacted with the compound or pharmaceutical composition thereof is breast tissue, bone marrow, lymph node, lymph tissue, spleen, or blood. In certain embodiments, the biological sample being contacted with the compound or pharmaceutical composition thereof is a tumor or cancerous tissue. In certain embodiments, the biological sample being contacted with the compound or pharmaceutical composition thereof is serum, cerebrospinal fluid, interstitial fluid, mucous, tears, sweat, pus, biopsied tissue (e.g., obtained by a surgical biopsy or needle biopsy), nipple aspirates, milk, vaginal fluid, saliva, swabs (such as buccal swabs), or any material containing biomolecules that is derived from the biological sample. [00261] In certain embodiments, the cell or tissue being contacted with the compound or pharmaceutical composition thereof is present in vitro. In certain embodiments, the cell or tissue being contacted with the compound or pharmaceutical composition thereof is present in vivo. In certain embodiments, the cell or tissue being contacted with the compound or pharmaceutical composition thereof is present ex vivo. In certain embodiments, the cell or tissue being contacted with the compound or pharmaceutical composition thereof is a malignant cell (e.g., malignant blood cell). In certain embodiments, the cell being contacted with the compound or pharmaceutical composition thereof is a malignant hematopoietic stem cell (e.g., malignant myeloid cell or malignant lymphoid cell). In certain embodiments, the cell being contacted with the compound or pharmaceutical composition thereof is a malignant lymphocyte (e.g., malignant T-cell or malignant B-cell). In certain embodiments, the cell being contacted with the compound or pharmaceutical composition thereof is a malignant white blood cell. In certain embodiments, the cell being contacted with the compound or pharmaceutical composition thereof is a malignant neutrophil, malignant macrophage, or malignant plasma cell. In certain embodiments, the cell being contacted with the compound or pharmaceutical composition thereof is a carcinoma cell. In certain embodiments, the cell being contacted with the compound or pharmaceutical composition thereof is a breast carcinoma cell. In certain embodiments, the cell being contacted with the compound or pharmaceutical composition thereof is a sarcoma cell. In certain embodiments, the cell being contacted with the compound or pharmaceutical composition thereof is a sarcoma cell from breast tissue. In certain embodiments, the biological sample is from tissue or cells with cancer (e.g., sarcoma, lung cancer, thyroid cancer, breast cancer, liver cancer, pancreatic cancer, gastric cancer, ovarian cancer, colon cancer, colorectal cancer, skin cancer, esophageal cancer; carcinoma). In certain embodiments, the biological sample is from tissue or cells with an inflammatory disease or autoimmune disease. In certain embodiments, the biological sample is from tissue or cells with cancer (e.g., sarcoma, lung cancer, thyroid cancer, breast cancer, liver cancer, pancreatic cancer, gastric cancer, ovarian cancer, colon cancer, colorectal cancer, skin cancer, esophageal cancer; carcinoma), an inflammatory disease, or an autoimmune disease. [00262] The disease (e.g., proliferative disease, inflammatory disease, autoimmune disease) to be treated or prevented using the compounds described herein may be associated with increased activity of a transcription factor, such as TEAD (e.g., TEAD1, TEAD2, TEAD3, TEAD4). The disease (e.g., proliferative disease, inflammatory disease, autoimmune disease) to be treated or prevented using the compounds described herein may be associated with the overexpression of a transcription factor, such as TEAD (e.g., TEAD1, TEAD2, TEAD3, TEAD4). [00263] In certain embodiments, the disease (e.g., proliferative disease, inflammatory disease, autoimmune disease) to be treated or prevented using the compounds described herein may be associated with the overexpression of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). A disease (e.g., proliferative disease, inflammatory disease, autoimmune disease) may be associated with aberrant activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). Aberrant activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) may be elevated and/or inappropriate or undesired activity of the transcription factor (e.g., TEAD). The compounds described herein, and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof, may inhibit the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) and be useful in treating and/or preventing diseases (e.g., proliferative diseases, inflammatory diseases, autoimmune diseases). The compounds described herein, and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co- crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof, may inhibit the activity of a transcription factor (e.g., TEAD) and be useful in treating and/or preventing diseases (e.g., proliferative disease, inflammatory disease, autoimmune disease). The compounds described herein, and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof, may inhibit the activity of a transcription factor (e.g., TEAD) and be useful in treating and/or preventing a disease (e.g., proliferative disease, inflammatory disease, autoimmune disease). [00264] All types of biological samples described herein or known in the art are contemplated as being within the scope of the invention. In certain embodiments, the disease (e.g., proliferative disease, inflammatory disease, autoimmune disease) to be treated or prevented using the compounds described herein is cancer. All types of cancers disclosed herein or known in the art are contemplated as being within the scope of the invention. In certain embodiments, the proliferative disease is a hematological malignancy. In certain embodiments, the proliferative disease is a blood cancer. In certain embodiments, the proliferative disease is a hematological malignancy. In certain embodiments, the proliferative disease is leukemia. In certain embodiments, the proliferative disease is chronic lymphocytic leukemia (CLL). In certain embodiments, the proliferative disease is acute lymphoblastic leukemia (ALL). In certain embodiments, the proliferative disease is T-cell acute lymphoblastic leukemia (T-ALL). In certain embodiments, the proliferative disease is chronic myelogenous leukemia (CML). In certain embodiments, the proliferative disease is acute myeloid leukemia (AML). In certain embodiments, the proliferative disease is acute monocytic leukemia (AMoL). In certain embodiments, the proliferative disease is Waldenström’s macroglobulinemia. In certain embodiments, the proliferative disease is Waldenström’s macroglobulinemia associated with the MYD88 L265P somatic mutation. In certain embodiments, the proliferative disease is myelodysplastic syndrome (MDS). In certain embodiments, the proliferative disease is a carcinoma. In certain embodiments, the proliferative disease is lymphoma. In certain embodiments, the proliferative disease is T-cell lymphoma. In some embodiments, the proliferative disease is Burkitt’s lymphoma. In certain embodiments, the proliferative disease is a Hodgkin’s lymphoma. In certain embodiments, the proliferative disease is a non-Hodgkin’s lymphoma. In certain embodiments, the proliferative disease is multiple myeloma. In certain embodiments, the proliferative disease is melanoma. In certain embodiments, the proliferative disease is colorectal cancer. In certain embodiments, the proliferative disease is colon cancer. In certain embodiments, the proliferative disease is breast cancer. In certain embodiments, the proliferative disease is recurring breast cancer. In certain embodiments, the proliferative disease is mutant breast cancer. In certain embodiments, the proliferative disease is HER2+ breast cancer. In certain embodiments, the proliferative disease is HER2- breast cancer. In certain embodiments, the proliferative disease is triple-negative breast cancer (TNBC). In certain embodiments, the proliferative disease is a bone cancer. In certain embodiments, the proliferative disease is osteosarcoma. In certain embodiments, the proliferative disease is Ewing’s sarcoma. In some embodiments, the proliferative disease is a brain cancer. In some embodiments, the proliferative disease is neuroblastoma. In some embodiments, the proliferative disease is a lung cancer. In some embodiments, the proliferative disease is small cell lung cancer (SCLC). In some embodiments, the proliferative disease is non-small cell lung cancer (NSCLC). In certain embodiments, the lung cancer is mesothelioma. In certain embodiments, the cancer is a thyroid cancer. In certain embodiments, the cancer is a sarcoma. In certain embodiments, the sarcoma is Kaposi’s sarcoma. In certain embodiments, the cancer is fallopian tube cancer. In certain embodiments, the cancer is a carcinoma. In certain embodiments, the carcinoma is fallopian tube carcinoma. In some embodiments, the proliferative disease is liver cancer. In some embodiments, the proliferative disease is prostate cancer. In some embodiments, the proliferative disease is pancreatic cancer. In some embodiments, the proliferative disease is gastric cancer. In some embodiments, the proliferative disease is ovarian cancer. In some embodiments, the proliferative disease is ovarian cancer. In some embodiments, the cancer is skin cancer. In some embodiments, the cancer is esophageal cancer. In certain embodiments, the cancer has a mutation in a gene of the Hippo signaling pathway. In certain embodiments, the cancer has a mutation in EGFR. In certain embodiments, the cancer has a mutation in MEK. In certain embodiments, the cancer is an EGFR-mutant non-small cell lung cancer. In certain embodiments, the cancer is resistant to certain anti-proliferative agents (e.g., cancers resistant to inhibitors of EGFR and/or MEK). In certain embodiments, the cancer is resistant to inhibitors of EGFR and/or MEK. In certain embodiments, the cancer is resistant to tyrosine kinase inhibitors (TKI’s). In some embodiments, the proliferative disease is a benign neoplasm. All types of benign neoplasms disclosed herein or known in the art are contemplated as being within the scope of the invention. In some embodiments, the proliferative disease is associated with angiogenesis. All types of angiogenesis disclosed herein or known in the art are contemplated as being within the scope of the invention. In certain embodiments, the cancer is a sarcoma, lung cancer, thyroid cancer, breast cancer, liver cancer, pancreatic cancer, gastric cancer, ovarian cancer, colon cancer, colorectal cancer, skin cancer, esophageal cancer; a carcinoma; has a mutation in a gene of the Hippo signaling pathway (e.g., has a mutation in EGFR, such as an EGFR-mutant non-small cell lung cancer, or has a mutation in MEK), is a cancer resistant to certain anti-proliferative agents (e.g., cancers resistant to inhibitors of EGFR and/or MEK), or is a cancer is resistant to tyrosine kinase inhibitors (TKI’s). In certain embodiments, the cancer to be treated with a compound described herein along with an additional pharmaceutical agent, for example, a modulator of another transcription factors (e.g., YAP, EGFR, MEK), is a cancer that has a mutation in a gene of the Hippo signaling pathway (e.g., has a mutation in EGFR, such as an EGFR-mutant non-small cell lung cancer, or has a mutation in MEK). In certain embodiments, the cancer to be treated with a compound described herein along with an additional pharmaceutical agent, for example, a modulator of another transcription factors (e.g., YAP, EGFR, MEK), is a cancer resistant to certain anti-proliferative agents (e.g., cancers resistant to inhibitors of EGFR and/or MEK). In certain embodiments, the cancer to be treated with a compound described herein along with an additional pharmaceutical agent, for example, a modulator of another transcription factors (e.g., YAP, EGFR, MEK), is a cancer is resistant to tyrosine kinase inhibitors (TKI’s). [00265] In certain embodiments, the inflammatory disease to be treated or prevented using the compounds described herein is fibrosis (e.g., idiopathic pulmonary fibrosis, liver cirrhosis, cystic fibrosis, systemic sclerosis, progressive kidney disease, or cardiovascular fibrosis). In certain embodiments, the autoimmune disease to be treated or prevented using the compounds described herein is sclerosis (e.g., systemic sclerosis (scleroderma) or multiple sclerosis). In certain embodiments, the autoimmune disease is amyotrophic lateral sclerosis. [00266] Another aspect of the disclosure relates to methods of inhibiting the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) in a biological sample (e.g., tissue, cell), or subject. In certain embodiments, the transcription factor is a TEAD. In certain embodiments, the TEAD is TEAD1. In certain embodiments, the TEAD is TEAD2. In certain embodiments, the TEAD is TEAD3. In certain embodiments, the TEAD is TEAD4. In certain embodiments, the activity of the transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) is aberrant activity of the transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). In certain embodiments, the activity of the transcription factor is increased activity of the transcription factor (e.g., TEAD). In certain embodiments, the inhibition of the activity of the transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) is irreversible. In other embodiments, the inhibition of the activity of the transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) is reversible. In certain embodiments, the methods of inhibiting the activity of the transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) include attaching a compound described herein to the transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). In certain embodiments, the methods comprise covalently modifying a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) by attaching a compound described herein to the transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). In certain embodiments, the methods comprise covalently inhibiting a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). In certain embodiments, the methods comprise reversibly inhibiting a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4). The present invention provides methods of inhibiting cell growth in a biological sample (e.g., tissue, cell), or subject. Another aspect of the disclosure relates to methods of inhibiting the transcription of a gene (e.g., a gene controlled or regulated by a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4)) in a biological sample (e.g., tissue, cell), or subject. [00267] In certain embodiments, the methods described herein include administering to a subject or contacting a biological sample with an effective amount of a compound described herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a pharmaceutical composition thereof. In certain embodiments, the methods described herein include administering to a subject or contacting a biological sample with an effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In certain embodiments, the compound is contacted with a biological sample. In certain embodiments, the compound is administered to a subject. In certain embodiments, the compound is administered in combination with one or more additional pharmaceutical agents described herein. The additional pharmaceutical agent may be an anti-proliferative agent. In certain embodiments, the additional pharmaceutical agent is an anti-cancer agent. The additional pharmaceutical agent may also be a transcription factor inhibitor. In certain embodiments, the additional pharmaceutical agent is a transcription factor inhibitor (e.g., inhibitor of EGFR and/or MEK). In certain embodiments, the additional pharmaceutical agent comprises an inhibitor of EGFR and an inhibitor of MEK. In certain embodiments, the additional pharmaceutical agent is a binder or inhibitor of TEAD (e.g., TEAD1, TEAD2, TEAD3, TEAD4)). In certain embodiments, the additional pharmaceutical agent is a binder or inhibitor of TEAD. In certain embodiments, the additional pharmaceutical agent is a binder or inhibitor of TEAD1. In certain embodiments, the additional pharmaceutical agent is a binder or inhibitor of TEAD2. In certain embodiments, the additional pharmaceutical agent is a binder or inhibitor of TEAD3. In certain embodiments, the additional pharmaceutical agent is a binder or inhibitor of TEAD4. In certain embodiments, the additional pharmaceutical agent is a selective binder of TEAD. In certain embodiments, the additional pharmaceutical agent is a selective binder of TEAD1. In certain embodiments, the additional pharmaceutical agent is a selective binder of TEAD2. In certain embodiments, the additional pharmaceutical agent is a selective binder of TEAD3. In certain embodiments, the additional pharmaceutical agent is a selective binder of TEAD4. In certain embodiments, the additional pharmaceutical agent is a selective inhibitor of TEAD. In certain embodiments, the additional pharmaceutical agent is a selective inhibitor of TEAD1. In certain embodiments, the additional pharmaceutical agent is a selective inhibitor of TEAD2. In certain embodiments, the additional pharmaceutical agent is a selective inhibitor of TEAD3. In certain embodiments, the additional pharmaceutical agent is a selective inhibitor of TEAD4. In certain embodiments, the additional pharmaceutical agent is a non- selective binder of TEAD1. In certain embodiments, the additional pharmaceutical agent is a non-selective binder of TEAD2. In certain embodiments, the additional pharmaceutical agent is a non-selective binder of TEAD3. In certain embodiments, the additional pharmaceutical agent is a non-selective binder of TEAD4. In certain embodiments, the additional pharmaceutical agent is a non-selective inhibitor of TEAD. In certain embodiments, the additional pharmaceutical agent is a non-selective inhibitor of TEAD1. In certain embodiments, the additional pharmaceutical agent is a non-selective inhibitor of TEAD2. In certain embodiments, the additional pharmaceutical agent is a non-selective inhibitor of TEAD3. In certain embodiments, the additional pharmaceutical agent is a non-selective inhibitor of TEAD4. In certain embodiments, the additional pharmaceutical agent is a selective inhibitor of EGFR. In certain embodiments, the additional pharmaceutical agent is a selective inhibitor of MEK. In certain embodiments, the additional pharmaceutical agent is a non-selective inhibitor of EGFR and/or MEK. In certain embodiments, the additional pharmaceutical agent includes an anti-cancer agent (e.g., chemotherapeutics), anti- inflammatory agent, steroids, immunosuppressant, radiation therapy, or other agents. In certain embodiments, the additional pharmaceutical agent is an anti-proliferative agent. In certain embodiments, the additional pharmaceutical agent is an inhibitor of a kinase. In certain embodiments, the additional pharmaceutical agent is a non-selective inhibitor of a kinase. In certain embodiments, the additional pharmaceutical agent is an immunotherapy agent (e.g., PD1 inhibitor, PDL1 inhibitor). In certain embodiments, the additional pharmaceutical agent is an immune checkpoint inhibitor. [00268] In some embodiments, the additional pharmaceutical agent is a topoisomerase inhibitor, a MCL1 inhibitor, a BCL-2 inhibitor, a BCL-xL inhibitor, a BRD4 inhibitor, a BRCA1 inhibitor, BRCA2 inhibitor, HER1 inhibitor, HER2 inhibitor, a CDK9 inhibitor, a Jumonji histone demethylase inhibitor, or a DNA damage inducer. In some embodiments, the additional pharmaceutical agent is etoposide, obatoclax, navitoclax, JQ1, 4-(((5’-chloro-2’- (((1R,4R)-4-(((R)-1-methoxypropan-2-yl)amino)cyclohexyl)amin o)-[2,4’-bipyridin]-6- yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile, JIB04, or cisplatin. Exemplary chemotherapeutic agents include alkylating agents such as nitrogen mustards, ethylenimines, methylmelamines, alkyl sulfonates, nitrosoureas, and triazenes; antimetabolites such as folic acid analogs, pyrimidine analogs, in particular fluorouracil and cytosine arabinoside, and purine analogs; natural products such as vinca alkaloids epi-podophyllotoxins, antibiotics, enzymes, and biological response modifiers; and miscellaneous products such as platinum coordination complexes, anthracenedione, substituted urea such as hydroxyurea, methyl hydrazine derivatives, and adrenocorticoid suppressant, including ABITREXATE (methotrexate), ABRAXANE (paclitaxel albumin-stabilized nanoparticle formulation), AC, AC-T, ADE, ADRIAMYCIN PFS (doxorubicin hydrochloride), ADRUCIL (fluorouracil), AFINITOR (everolimus), AFINITOR DISPERZ (everolimus), ALDARA (imiquimod), ALIMTA (pemetrexed disodium), AREDIA (pamidronate disodium), ARIMIDEX (anastrozole), AROMASIN (exemestane), AVASTIN (bevacizumab), BECENUM (carmustine), BEP, BICNU (carmustine), BLENOXANE (bleomycin), CAF, CAMPTOSAR (irinotecan hydrochloride), CAPOX, CAPRELSA (vandetanib), CARBOPLATIN-TAXOL, CARMUBRIS (carmustine), CASODEX (bicalutamide), CEENU (lomustine), CERUBIDINE (daunorubicin hydrochloride), CERVARIX (recombinant HPV bivalent vaccine), CLAFEN (cyclophosphamide), CMF, COMETRIQ (cabozantinib-s-malate), COSMEGEN (dactinomycin), CYFOS (ifosfamide), CYRAMZA (ramucirumab), CYTOSAR-U (cytarabine), CYTOXAN (cyclophosphamide), DACOGEN (decitabine), DEGARELIX, DOXIL (doxorubicin hydrochloride liposome), DOXORUBICIN HYDROCHLORIDE, DOX-SL (doxorubicin hydrochloride liposome), DTIC-DOME (dacarbazine), EFUDEX (fluorouracil), ELLENCE (epirubicin hydrochloride), ELOXATIN (oxaliplatin), ERBITUX (cetuximab), ERIVEDGE (vismodegib), ETOPOPHOS (etoposide phosphate), EVACET (doxorubicin hydrochloride liposome), FARESTON (toremifene), FASLODEX (fulvestrant), FEC, FEMARA (letrozole), FLUOROPLEX (fluorouracil), FOLEX (methotrexate), FOLEX PFS (methotrexate), FOLFIRI , FOLFIRI- BEVACIZUMAB, FOLFIRI-CETUXIMAB, FOLFIRINOX, FOLFOX, FU-LV, GARDASIL (recombinant human papillomavirus (HPV) quadrivalent vaccine), GEMCITABINE-CISPLATIN, GEMCITABINE-OXALIPLATIN, GEMZAR (gemcitabine hydrochloride), GILOTRIF (afatinib dimaleate), GLEEVEC (imatinib mesylate), GLIADEL (carmustine implant), GLIADEL WAFER (carmustine implant), HERCEPTIN (trastuzumab), HYCAMTIN (topotecan hydrochloride), IFEX (ifosfamide), IFOSFAMIDUM (ifosfamide), INLYTA (axitinib), INTRON A (recombinant interferon alfa-2b), IRESSA (gefitinib), IXEMPRA (ixabepilone), JAKAFI (ruxolitinib phosphate), JEVTANA (cabazitaxel), KADCYLA (ado-trastuzumab emtansine), KEYTRUDA (pembrolizumab), KYPROLIS (carfilzomib), LIPODOX (doxorubicin hydrochloride liposome), LUPRON (leuprolide acetate), LUPRON DEPOT (leuprolide acetate), LUPRON DEPOT-3 MONTH (leuprolide acetate), LUPRON DEPOT-4 MONTH (leuprolide acetate), LUPRON DEPOT-PED (leuprolide acetate), MEGACE (megestrol acetate), MEKINIST (trametinib), METHAZOLASTONE (temozolomide), METHOTREXATE LPF (methotrexate), MEXATE (methotrexate), MEXATE-AQ (methotrexate), MITOXANTRONE HYDROCHLORIDE, MITOZYTREX (mitomycin c), MOZOBIL (plerixafor), MUSTARGEN (mechlorethamine hydrochloride), MUTAMYCIN (mitomycin c), MYLOSAR (azacitidine), NAVELBINE (vinorelbine tartrate), NEOSAR (cyclophosphamide), NEXAVAR (sorafenib tosylate), NOLVADEX (tamoxifen citrate), NOVALDEX (tamoxifen citrate), OFF, PAD, PARAPLAT (carboplatin), PARAPLATIN (carboplatin), PEG-INTRON (peginterferon alfa-2b), PEMETREXED DISODIUM, PERJETA (pertuzumab), PLATINOL (cisplatin), PLATINOL- AQ (cisplatin), POMALYST (pomalidomide), prednisone, PROLEUKIN (aldesleukin), PROLIA (denosumab), PROVENGE (sipuleucel-t), REVLIMID (lenalidomide), RUBIDOMYCIN (daunorubicin hydrochloride), SPRYCEL (dasatinib), STIVARGA (regorafenib), SUTENT (sunitinib malate), SYLATRON (peginterferon alfa-2b), SYLVANT (siltuximab), SYNOVIR (thalidomide), TAC, TAFINLAR (dabrafenib), TARABINE PFS (cytarabine), TARCEVA (erlotinib hydrochloride), TASIGNA (nilotinib), TAXOL (paclitaxel), TAXOTERE (docetaxel), TEMODAR (temozolomide), THALOMID (thalidomide), TOPOSAR (etoposide), TORISEL (temsirolimus), TPF, TRISENOX (arsenic trioxide), TYKERB (lapatinib ditosylate), VECTIBIX (panitumumab), VEIP, VELBAN (vinblastine sulfate), VELCADE (bortezomib), VELSAR (vinblastine sulfate), VEPESID (etoposide), VIADUR (leuprolide acetate), VIDAZA (azacitidine), VINCASAR PFS (vincristine sulfate), VOTRIENT (pazopanib hydrochloride), WELLCOVORIN (leucovorin calcium), XALKORI (crizotinib), XELODA (capecitabine), XELOX, XGEVA (denosumab), XOFIGO (radium 223 dichloride), XTANDI (enzalutamide), YERVOY (ipilimumab), ZALTRAP (ziv-aflibercept), ZELBORAF (vemurafenib), ZOLADEX (goserelin acetate), ZOMETA (zoledronic acid), ZYKADIA (ceritinib), ZYTIGA (abiraterone acetate), ENMD- 2076, PCI-32765, AC 2 20, dovitinib lactate (TKI258, CHIR-258), BIBW 2992 (TOVOK TM ), SGX523, PF-04217903, PF-02341066, PF-299804, BMS-777607, ABT-869, MP470, BIBF 1120 (VARGATEF®), AP24534, JNJ-26483327, MGCD265, DCC-2036, BMS-690154, CEP-11981, tivozanib (AV-951), OSI-930, MM-121, XL-184, XL-647, and/or XL228), proteasome inhibitors (e.g., bortezomib (Velcade)), mTOR inhibitors (e.g., rapamycin, temsirolimus (CCI-779), everolimus (RAD-001), ridaforolimus, AP23573 (Ariad), AZD8055 (AstraZeneca), BEZ235 (Novartis), BGT226 (Norvartis), XL765 (Sanofi Aventis), PF- 4691502 (Pfizer), GDC0980 (Genentech), SF1126 (Semafoe) and OSI-027 (OSI)), oblimersen, gemcitabine, carminomycin, leucovorin, pemetrexed, cyclophosphamide, dacarbazine, procarbizine, prednisolone, dexamethasone, campathecin, plicamycin, asparaginase, aminopterin, methopterin, porfiromycin, melphalan, leurosidine, leurosine, chlorambucil, trabectedin, procarbazine, discodermolide, carminomycin, aminopterin, and hexamethyl melamine. Exemplary chemotherapeutic agents also include anthracycline antibiotics, actinomycin D, plicamycin, puromycin, gramicidin D, paclitaxel, colchicine, cytochalasin B, emetine, maytansine, amsacrine, cisplatin, carboplatin, mitomycin, altretamine, cyclophosphamide, lomustine, and carmustine. In certain embodiments, a pharmaceutical composition described herein further comprises a combination of the additional pharmaceutical agents described herein. [00269] The disclosed compounds or pharmaceutical compositions thereof used with an additional pharmaceutical agent may synergistically augment inhibition (e.g., increase the degree of inhibition) of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) induced by the additional pharmaceutical agent(s) in the biological sample or subject. For example, use of the disclosed compounds or pharmaceutical compositions thereof with an additional pharmaceutical agent may increase the degree of inhibition of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) compared to the degree of inhibition of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) induced by the additional pharmaceutical agent alone. Thus, the combination of the disclosed compounds or compositions and the additional pharmaceutical agent(s) may be useful in treating proliferative diseases resistant to a treatment using the additional pharmaceutical agent(s) without the disclosed compounds or compositions. [00270] In some embodiments, the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) is non-selectively inhibited by the compounds or pharmaceutical compositions described herein. In some embodiments, the activity of the transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) being inhibited is selectively inhibited by the compounds or pharmaceutical compositions described herein, compared to the activity of a different protein (e.g., a different transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4)). In certain embodiments, the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4)) is selectively inhibited by a compound or pharmaceutical composition described herein, compared to the activity of a different protein. In certain embodiments, the activity of TEAD1 is selectively inhibited by a compound or pharmaceutical composition described herein, compared to the activity of another TEAD (e.g., TEAD2, TEAD3, TEAD4). In certain embodiments, the activity of TEAD2 is selectively inhibited by a compound or pharmaceutical composition described herein, compared to the activity of another TEAD (e.g., TEAD1, TEAD3, TEAD4). In certain embodiments, the activity of TEAD3 is selectively inhibited by a compound or pharmaceutical composition described herein, compared to the activity of another TEAD (e.g., TEAD1, TEAD2, TEAD4). In certain embodiments, the activity of TEAD4 is selectively inhibited by a compound or pharmaceutical composition described herein, compared to the activity of another TEAD (e.g., TEAD1, TEAD2, TEAD3). [00271] The selectivity of a compound or pharmaceutical composition described herein in inhibiting the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) over a different protein (e.g., a different transcription factor (e.g., TEAD)) may be measured by the quotient of the IC 5 0 value of the compound or pharmaceutical composition in inhibiting the activity of the different protein over the IC 50 value of the compound or pharmaceutical composition in inhibiting the activity of the transcription factor (e.g., TEAD). The selectivity of a compound or pharmaceutical composition described herein for a protein transcription factor (e.g., TEAD) over a different protein may also be measured by the quotient of the K d value of an adduct of the compound or pharmaceutical composition and the different protein over the Kd value of an adduct of the compound or pharmaceutical composition and the transcription factor (e.g., TEAD). In certain embodiments, the selectivity is at least 2-fold, at least 3-fold, at least 5-fold, at least 10-fold, at least 30-fold, at least 100- fold, at least 300-fold, at least 1,000-fold, at least 3,000-fold, at least 10,000-fold, at least 30,000-fold, or at least 100,000-fold. In certain embodiments, the selectivity is not more than 100,000-fold, not more than 10,000-fold, not more than 1,000-fold, not more than 100-fold, not more than 10-fold, or not more than 2-fold. Combinations of the above-referenced ranges (e.g., at least 2-fold and not more than 10,000-fold) are also within the scope of the disclosure. [00272] In certain embodiments, a kit described herein includes a first container comprising a compound or pharmaceutical composition described herein. In certain embodiments, a kit described herein is useful in treating and/or preventing a disease, such as a proliferative disease (e.g., cancers (e.g., carcinoma, sarcoma); lung cancer, breast cancer, liver cancer, pancreatic cancer, gastric cancer, ovarian cancer, colon cancer, colorectal cancer, skin cancer, esophageal cancer)), inflammatory disease (e.g., fibrosis), or autoimmune disease (e.g., sclerosis), in a subject in need thereof, inhibiting the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4), and/or inhibiting the transcription of a gene (e.g., a gene controlled or regulated by a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4)) in a subject, and/or biological sample (e.g., tissue, cell). [00273] In certain embodiments, a kit described herein further includes instructions for using the compound or pharmaceutical composition included in the kit. A kit described herein may also include information as required by a regulatory agency such as the U.S. Food and Drug Administration (FDA). In certain embodiments, the information included in the kits is prescribing information. In certain embodiments, the kits and instructions provide for treating a proliferative disease in a subject in need thereof, preventing a disease, such as a proliferative disease, inflammatory disease, autoimmune disease in a subject in need thereof, inhibiting the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4)) in a subject and/or biological sample (e.g., tissue, cell), and/or inhibiting the transcription of a gene (e.g., a gene controlled or regulated by a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4)). A kit described herein may include one or more additional pharmaceutical agents described herein as a separate composition. E XAMPLES [00274] In order that the disclosure described herein may be more fully understood, the following examples are set forth. The synthetic and biological examples described in this application are offered to illustrate the compounds, pharmaceutical compositions, and methods provided herein and are not to be construed in any way as limiting their scope. Example 1. Biological Assays [00275] The compounds were evaluated in vitro. An anti-palmitoylation assay was conducted, and the results are shown in Figure 1. In addition, an anti-proliferation assay was performed using NCI-H 2 26 cells (Figure 2). The IC 5 0 values of certain compounds are shown below in Table 1. Table 1. IC 5 0 values of certain compounds of the disclosure. Gel-based anti-palmitoylation assay [00276] The mixture of 2-fluoro-5-nitrobenzonitrile (1 g, 6.0 mmol), cyclohexanamine (0.61 μM His-tag TEAD-YBD recombinant protein was incubated with inhibitors at the indicated concentrations at 37 °C for 2 h followed by the addition of palmitoyl alkyne- coenzyme A (Cayman chemical, no.15968) in a total volume of 50 μL. After 30 min reaction, 5 μL 10%SDS were added and 5 μL click reagents were added to start click reaction. After another 1 h, 4x loading buffer were added to the reaction mixture and the samples subjected for western blot analysis. IRDye 800CW Streptavidin (LI-COR, no. 92632230) and His-Tag Mouse mAb (Cell Signaling, no.2366S) was used for biotin detection and His-tag detection. The blots were imaged on Odyssey CLx Imager (LI-COR). Antiproliferation assay [00277] The mixture of 2-fluoro-5-nitrobenzonitrile (1 g, 6.0 mmol), cyclohexanamine (0.6For 2D adherent cell viability experiment, the cells were seeded at 384-well plate (Corning, no.3570) at the density of 200 cells/well. The next day, compounds were added using Janus workstation (PerkinElmer). After 5 days treatment, the cell viability was measured by CellTiter-Glo kit (Promega, no. G7570) as the manufacturer recommended. Example 2. Synthesis of compounds Scheme 1. Synthesis of Compound (A-17) Step 1: Synthesis of 2-(cyclohexylamino)-5-nitrobenzonitrile (Compound 3) [00278] The mixture of 2-fluoro-5-nitrobenzonitrile (1 g, 6.0 mmol), cyclohexanamine (0.6 g, 6.0 mmol) and TEA (1.2 g, 12.0 mmol) in DMAc (5 mL) was heated at 120 o C under N 2 for 16 hours, until all starting material was consumed as showed by LCMS. The mixture was then concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 50% v/v) to afford the target compound 3 as solid (1.4 g, yield 94.9%). LC-MS (ESI) m/z: 246 [M+H] + . Step 2: Synthesis of N-cyclohexyl-4-nitro-2-(2H-tetrazol-5-yl) aniline (Compound 4) [00279] The mixture of 2-(cyclohexylamino)-5-nitrobenzonitrile (1.3 g, 5.3 mmol) and NaN 3 (0.52 g, 7.9 mmol) in DMF (30 mL) was heated at 120 o C under N 2 for 16 hours, until all starting material was consumed as showed by LCMS. The mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 20% v/v) to obtain the target compound 4 as solid (800 mg, yield 52.3%). LC-MS (ESI) m/z: 289 [M+H] + . Step 3: Synthesis of N-cyclohexyl-2-(2-(2-fluorobenzyl)-2H-tetrazol-5-yl)-4-nitro aniline (Compound 6) [00280] The mixture of N-cyclohexyl-4-nitro-2-(2H-tetrazol-5-yl)aniline (700 mg, 2.43 mmol), 1-(bromomethyl)-2-fluorobenzene (456 mg, 2.43 mmol) and K2CO 3 (670 mg, 4.86 mmol) in DMF (20 mL) was stirred at rt under N2 for 3 hours. The mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 40% v/v) to obtain the target compound 6 as solid (600 mg, yield 62.3%). LC-MS (ESI) m/z: 397 [M+H] + . Step 4: Synthesis of N1-cyclohexyl-2-(2-(2-fluorobenzyl)-2H-tetrazol-5-yl)benzene -1,4- diamine (Compound 7) [00281] To the solution of N-cyclohexyl-2-(2-(2-fluorobenzyl)-2H-tetrazol-5-yl)-4- nitroaniline (500 mg, 1.26 mmol) in EtOH (15 mL) and THF (15 mL) was added Raney nickel (53 mg, 0.13 mmol), and then N2H4·H 2 O (63 mg, 1.26 mmol) was added. The mixture was stirred at rt for 1 hour and filtered, the filtrate was concentrated under reduced pressure to leave the crude compound 7 as oil (400 mg, yield 86.5%). LC-MS (ESI) m/z: 367 [M+H] + . Step 5: Synthesis of N-(4-(cyclohexylamino)-3-(2-(2-fluorobenzyl)-2H-tetrazol-5- yl)phenyl)acrylamide (A-17) [00282] To the mixture of N1-cyclohexyl-2-(2-(2-fluorobenzyl)-2H-tetrazol-5-yl)benzene - 1,4-diamine (450 mg, 1.23 mmol) and Et3N (249 mg, 2.46 mmol) in THF (15 mL) was added acryloyl chloride (110 mg, 1.23 mmol), the mixture was stirred at 0 o C for 1 hour, concentrated and purified by preparative HPLC (MeCN/H 2 O/TFA) to afford the target A-17 as solid (490 mg, yield 95.0%). LC-MS (ESI) m/z: 421.3 [M+H] + . 1 H-NMR (400 MHz, DMSO-d6) δ (ppm): 10.00 (s, 1H), 8.34 (d, J = 2.5 Hz, 1H), 7.65 (dd, J = 9.0, 2.5 Hz, 1H), 7.57 (t, J = 7.6 Hz, 1H), 7.53-7.43(m, 1H), 7.29 (dd, J = 15.6, 7.9 Hz, 2H), 6.82 (dd, J = 13.5, 8.5 Hz, 2H), 6.39 (dd, J = 16.9, 10.1 Hz, 1H), 6.21 (dd, J = 17.0,2.0 Hz, 1H), 6.08 (s, 2H), 5.69 (dd, J = 10.1, 2.0 Hz, 1H), 3.48 (s, 1H), 2.0-1.75 (br, 2H), 1.70-1.50 (m, 3H), 1.47- 1.32(m,2H), 1.32-1.15 (m,3H). 19 F-NMR (376 MHz, DMSO-d6) δ (ppm): 117.43. Scheme 2. Synthesis of Compound (A-18) Step 1: Synthesis of 2-(cyclohexylamino)-5-nitrobenzoic acid (Compound 2.3) [00283] The mixture of 2-fluoro-5-nitrobenzoic acid (1 g, 5.4 mmol) and cyclohexanamine (535 mg, 5.4 mmol) in pyridine (20 mL) was heated at 60 o C Under N2 for 16 hours. The resulting mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 30% v/v) to afford the target compound 2.3 as solid (1.5 g, yield 99.9%). LC-MS (ESI) m/z: 265 [M+H] + . Step 2: Synthesis of 2-(cyclohexylamino)-5-nitrobenzohydrazide (Compound 2.4) [00284] The mixture of 2-(cyclohexylamino)-5-nitrobenzoic acid (1.4 g, 0.19 mmol) in EtOH (30 mL) and H 2 SO 4 (30 mL) was heated at 100 o C for 16 hours. The resulting mixture was concentrated in vacuum, the residue was adjusted to pH 9 with concentrated ammonia solution and extracted with ether (100 mL x 2), the combined extracts were dried over anhydrous Na2SO 4 , filtered and concentrated in vacuum, to the residue was added hydrazine hydrate (98%, 1 mL), the resulting mixture was heated at 120 o C for 3 hours, concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 30% v/v) to obtain the target compound 2.4 as oil (700 mg, yield 36.6%). LC-MS (ESI) m/z: 279[M+H] + . Step 3: Synthesis of N-cyclohexyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-4-nitroanilin e (Compound 2.6) [00285] The mixture of 2-(cyclohexylamino)-5-nitrobenzohydrazide (650 mg, 2.34 mmol) and 1,1,1-triethoxyethane (379 mg, 2.34 mmol) in 1,4-dioxane (30 mL) was heated at 110 o C for 16 hours. The resulting mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 50% v/v) to obtain the target compound 2.6 as solid (600 mg, yield 84.9%). LC-MS (ESI) m/z: 303[M+H] + . Step 4: Synthesis of N1-cyclohexyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)benzene-1,4- diamine (Compound 2.7) [00286] To the solution of N-cyclohexyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-4-nitroanilin e (550 mg, 1.82 mmol) in EtOH (15 mL) and THF (15 mL) was added Raney nickel (88 mg, 0.18 mmol), and then N 2 H 4 ·H 2 O (110 mg, 1.82 mmol). The resulting mixture was stirred at rt for 1 hour and filtered, the filtrate was concentrated under reduced pressure to leave the crude target compound 2.7 as oil (500 mg, yield 99.9%). LC-MS (ESI) m/z: 273[M+H] + . Step 5: Synthesis of N-(4-(cyclohexylamino)-3-(5-methyl-1,3,4-oxadiazol-2- yl)phenyl)acrylamide (Compound (A-18)) [00287] To the mixture of N1-cyclohexyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)benzene-1,4- diamine (450 mg, 1.65 mmol) and Et 3 N (100 mg, 3.31 mmol) in THF (20 mL) was added acryloyl chloride (64 mg, 1.65 mmol), the resulting mixture was stirred at 0 o C for 1 hour, concentrated and monitored by preparative HPLC (MeCN/H 2 O/TFA) to obtain the target compound (A-18) as solid (314 mg, yield 58.2%). LC-MS (ESI) m/z: 327 [M+H] + . 1 H-NMR (400 MHz, DMSO-d6) δ (ppm): 10.03 (s, 1H), 8.22 (d, J = 2.5 Hz, 1H), 7.57 (dd, J = 9.1, 2.5 Hz, 1H), 7.32 (d, J = 7.7 Hz, 1H), 6.90 (d, J = 9.2 Hz, 1H), 6.39 (dd, J = 16.5, 9.6 Hz, 1H), 6.22 (dd, J = 17.0, 2.1 Hz, 1H), 5.71 (dd, J = 10.0, 2.1 Hz, 1H), 3.55-3.50 (br, 1H), 2.59 (s, 3H), 1.97 (d, J = 9.7 Hz, 2H), 1.75-1.65 (m, 2H), 1.60-1.50 (m, 1H), 1.50-1.35 (m, 2H), 1.35- 1.26 (m, 3H). Scheme 3. Synthesis of Compound (A-19) Step 1: Synthesis of 4-iodo-1-(3-(trifluoromethyl)benzyl)-1H-imidazole (Compound 3.3) [00288] To the solution of 5-iodo-1H-imidazole (1 g, 5.18 mmol) in DMF (20 mL) was added NaH (248 mg, 6.2 mmol) under N 2 , the mixture was stirred at 0 o C for 0.5 hour, and then 1-(bromomethyl)-3-(trifluoromethyl)benzene (1.24 g, 5.18 mmol) was added, the resulting mixture was stirred at rt for 1 hours, concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 30% v/v) to obtain the target compound 3.3 as solid (1.5 g, yield 82.8%). LC-MS (ESI) m/z: 353[M+H] + . Step 2: Synthesis of N-cyclohexyl-4-nitro-2-(1-(3-(trifluoromethyl)benzyl)-1H-imi dazol- 4-yl)aniline (Compound 3.5) [00289] The mixture of 4-iodo-1-(3-(trifluoromethyl)benzyl)-1H-imidazole (300 mg, 0.96 mmol), N-cyclohexyl-4-nitro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborol an-2-yl)aniline (300 mg, 0.96 mmol), Cs 2 CO 3 (828 mg, 2.52 mmol) and Pd(dppf)Cl 2 (62.4 mg, 0.096 mmol) in DMF (2 mL) was heated at 100 o C under N 2 for 16 hours. The resulting mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 30% v/v) to obtain the target compound 3.5 as solid (120 mg, yield 31.7%). LC-MS (ESI) m/z: 445[M+H] + . Step 3: Synthesis of N1-cyclohexyl-2-(1-(3-(trifluoromethyl)benzyl)-1H-imidazol-4 - yl)benzene-1,4-diamine (Compound 3.6) [00290] To the solution of N-cyclohexyl-4-nitro-2-(1-(3-(trifluoromethyl)benzyl)-1H- imidazol-4-yl)aniline (90 mg, 0.18 mmol) in EtOH (10 mL) and THF (10 mL) was added Raney nickel (12 mg, 0.03 mmol), followed by N2H4·H 2 O (9 mg, 0.18 mmol). The mixture was stirred at rt for 1 hour and filtered, the filtrate was concentrated under reduced pressure to leave crude target compound 3.6 as oil (60 mg, yield 71.5%). LC-MS (ESI) m/z: 415[M+H] + . Step 4: Synthesis of N-(4-(cyclohexylamino)-3-(1-(3-(trifluoromethyl)benzyl)-1H- imidazol-4-yl)phenyl)acrylamide (Compound (A-19)) [00291] To the mixture of N1-cyclohexyl-2-(1-(3-(trifluoromethyl)benzyl)-1H-imidazol-4 - yl)benzene-1,4-diamine (50 mg, 0.12 mmol) and Et 3 N (24 mg, 0.24 mmol) in THF (10 mL) was added acryloyl chloride (18 mg, 0.12 mmol), the mixture was stirred at 0 o C for 1 hour, concentrated and purified by preparative HPLC (MeCN/H 2 O/TFA) to afford the target Compound (A-19) as solid (5 mg, yield 8.8%). LC-MS (ESI) m/z: 469[M+H] + . 1 H-NMR (400 MHz, CD 3 OD) δ (ppm): 7.89 (s, 1H), 7.70 – 7.54 (m, 5H), 7.40 (s, 1 H), 7.32 (dd, J = 8.8, 2.4 Hz, 1H), 6.76 (d, J = 8.4 Hz, 1H), 6.41 (dd, J = 16.8, 10.0 Hz, 1H), 6.31 (dd, J = 16.8, 2.0 Hz, 1H), 5.73 (dd, J = 9.8, 2.1 Hz, 1H), 5.40 (s, 2H), 2.06-1.96 (m, 2H), 1.80-1.70 (m, 2H), 1.68- 1.58 (m, 1H), 1.50-1.21 (m, 6H). Scheme 4. Synthesis of Compound (A-20) Step 1: Synthesis of 5-nitro-2-(4-(trifluoromethyl)phenylamino)benzonitrile (Compound 4.3) [00292] To the solution of 4-(trifluoromethyl) aniline (0.96 mg, 6.0 mmol) in DMF (20 mL) was added NaH (0.29 g, 7.2 mmol), the mixture was stirred at 0 o C under N2 for 0.5 hour, and then 2-fluoro-5-nitrobenzonitrile (1 g, 6.0 mmol) was added. The resulting mixture was stirred at 120 o C for 16 hours, concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 30% v/v) to afford the target compound 4.3 as solid (500 mg, yield 27.1%). LC-MS (ESI) m/z: 308 [M+H] + . Step 2: Synthesis of 4-nitro-2-(2H-tetrazol-5-yl)-N-(4-(trifluoromethyl)phenyl)an iline (Compound 4.4) [00293] The mixture of 5-nitro-2-(4-(trifluoromethyl)phenylamino)benzonitrile (400 mg, 1.30 mmol) and NaN 3 (127 mg, 1.95 mmol) in DMF (20 mL) was heated at 120 o C for 16 hours. The resulting mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 30% v/v) to obtain the target compound 4.4 as solid (300 mg, yield 65.7%). LC-MS (ESI) m/z: 351 [M+H] + . Step 3: Synthesis of 2-(2-(2-fluorobenzyl)-2H-tetrazol-5-yl)-4-nitro-N-(4- (trifluoromethyl)phenyl)aniline (Compound 4.6) [00294] The mixture of 4-nitro-2-(2H-tetrazol-5-yl)-N-(4-(trifluoromethyl)phenyl)an iline (250 mg, 0.71 mmol), 1-(bromomethyl)-2-fluorobenzene (134 mg, 0.71 mmol) and K2CO 3 (196 mg, 1.42 mmol) in DMF (15 mL) was stirred at rt for 3 hours. The resulting mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 40% v/v) to obtain the target compound 4.6 as solid (300 mg, yield 91.7%). LC-MS (ESI) m/z: 459 [M+H] + . Step 4: Synthesis of 2-(2-(2-fluorobenzyl)-2H-tetrazol-5-yl)-N-1-(4- (trifluoromethyl)phenyl)benzene-1,4-diamine (Compound 4.7) [00295] To the solution of 2-(2-(2-fluorobenzyl)-2H-tetrazol-5-yl)-4-nitro-N-(4- (trifluoromethyl)phenyl)aniline (250 mg, 0.55 mmol) in EtOH (10 mL) and THF (10 mL) was added Raney nickel (20 mg, 0.05 mmol), and then N2H4·H 2 O (27 mg, 0.55 mmol) was added. The mixture was stirred at rt for 1 hour and filtered, the filtrate was concentrated under reduced pressure to leave the crude compound 4.7 as oil (200 mg, yield 71.4%). LC- MS (ESI) m/z: 429 [M+H] + . Step 5: Synthesis of N-(3-(2-(2-fluorobenzyl)-2H-tetrazol-5-yl)-4-(4- (trifluoromethyl)phenylamino)phenyl)acrylamide (Compound (A-20)) [00296] To the mixture of 2-(2-(2-fluorobenzyl)-2H-tetrazol-5-yl)-N1-(4-(trifluorometh yl) phenyl)benzene-1,4-diamine (200 mg, 0.47 mmol) and Et3N (97 mg, 0.94 mmol) in THF (15 mL) was added acryloyl chloride (42 mg, 0.47 mmol), the mixture was stirred at 0 o C for 1 hour, concentrated and purified by preparative HPLC (MeCN/H 2 O/TFA) to obtain the target Compound (I-13) as solid (171 mg, yield 76.0%). LC-MS (ESI) m/z: 483 [M+H] + . 1 H-NMR (400 MHz, DMSO-d6) δ (ppm) 10.32 (s, 1H), 8.59 (s, 1H), 8.37 (d, J = 2.4 Hz, 1H), 7.83 (dd, J = 9.1, 2.3 Hz, 1H), 7.49 (dd, J = 8.1, 3.8 Hz, 5H), 7.34 – 7.18 (m, 2H), 7.03 (d, J = 8.7 Hz, 2H), 6.43 (dd, J = 17.0, 10.1 Hz, 1H), 6.27 (dd, J = 17.0, 2.0 Hz, 1H), 6.04 (s, 2H), 5.77 (dd, J = 10.1, 2.0 Hz, 1H). 19 F-NMR (376 MHz, DMSO-d6) δ (ppm): 117.53. Scheme 5. Synthesis of A-1 Step 1: Synthesis of 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxabo rolane (Compound 5.2) [00297] The mixture of 2-bromo-1-fluoro-4-nitrobenzene (2 g, 9.2 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) ( 1.2 g, 10 mmol), KOAc (1.8 g, 18.4 mmol) and Pd(dppf)Cl 2 (336 mg, 0.44 mmol) in 1,4-dioxane (50 mL) and DMSO (5 mL) was heated at 90 o C under N2 for 14 hours. The mixture was diluted with water (100 mL) and extracted with EtOAc (100 mL x 3), the combined organics were washed with brine (100 mL), dried over anhydrous Na 2 SO 4 , filtered and concentrated to leave the crude compound 5.2 as oil (1.6g, yield 65.6%). LC-MS (ESI) m/z: No mass. Step 2: Synthesis of 2-(2-fluoro-5-nitrophenyl)thiazole (Compound 5.3) [00298] The mixture of 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxabo rolane (800 mg, 3.0 mmol), 2-bromopyrimidine (486 mg, 3.0 mmol), K3PO 4 (1.9 g, 9.0 mmol), Pd2(dppf)Cl2 (108 mg, 0.15 mmol) in Me2CHOH (10 mL), PhMe (6 mL) and H 2 O (6 mL) was heated at 85 o C for 4 hours. The resulted mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 25% v/v) to obtain compound 5.3 as solid (150 mg, yield 22%). LC-MS (ESI) m/z: 225[M+H] + . Step 3: Synthesis of 2-(thiazol-2-yl)-N1-(4-(trifluoromethyl)phenyl)benzene-1,4- diamine(Compound 5.4) [00299] To the mixture of 2-(2-fluoro-5-nitrophenyl)thiazole (150 mg, 0.67 mmol) in DMF (5 mL) was added NaH (60%, 53 mg, 1.34 mmol), the mixture was stirred at 0 o C under N 2 for 0.5 hour, and then 4-(trifluoromethyl)aniline (107 mg, 0.67mmol) was added in one portion. The mixture was stirred at rt for 16 hours, concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether=30% v/v) to obtain the target compound 5.4 as solid (30 mg, yield 12%). LC-MS (ESI) m/z: 366[M+H] + . Step 4: Synthesis of 2-(thiazol-2-yl)-N1-(4-(trifluoromethyl)phenyl)benzene-1,4-d iamine (Compound 5.5) [00300] To the solution of 4-nitro-2-(thiazol-2-yl)-N-(4-(trifluoromethyl)phenyl)anilin e (30 mg, 0.082 mmol) in EtOH (2 mL) and THF (2 mL) was added Raney nickel (16 mg, 0.04 mmol), and then N 2 H 4 ·H 2 O (20 mg, 0.42 mmol) was added, the mixture was stirred at rt for 1 hour, filtered and concentrated at reduced pressure to leave the crude compound 5.5 as oil (22 mg, yield 80%). LC-MS (ESI) m/z: 336[M+H] + . Step 5: Synthesis of N-(3-(thiazol-2-yl)-4-(4- (trifluoromethyl)phenylamino)phenyl)acrylamide (A-1) [00301] To the mixture of 2-(thiazol-2-yl)-N1-(4-(trifluoromethyl)phenyl)benzene-1,4- diamine (22 mg, 0.06 mmol) and Et 3 N (12 mg, 0.12 mmol) in THF (10 mL) was added acryloyl chloride (6 mg, 0.06 mmol), the mixture was stirred at 0 o C for 1 hour, and then concentrated and purified by prep-HPLC (MeCN/TFA/H 2 O) to obtain the target compound A-1 as solid (15 mg, yield 64%). LC-MS (ESI) m/z: 390 [M+H] + . 1 H NMR (400 MHz, CD3OD) δ (ppm) 8.39 (d, J = 2.4 Hz, 1H), 7.93 (d, J = 3.4 Hz, 1H), 7.66 – 7.48 (m, 5H), 7.20 (d, J = 8.5 Hz, 2H), 6.43 (qd, J = 17.0, 5.9 Hz, 2H), 5.81 (dd, J = 9.5, 2.4 Hz, 1H). Scheme 6. Synthesis of A-2 Step 1: Synthesis of methyl 2-(4-(trifluoromethyl)phenylamino)benzoate (Compound 6.2) [00302] The mixture of 4-(trifluoromethyl)aniline (2 g, 9.3 mmol), methyl 2- bromobenzoate (1.2 g, 7.5 mmol), Cs2CO 3 (3.34 mg, 10.2 mmol) and Pd2(dba)3 (0.085 mg, 0.093 mmol) in toluene (20 mL) was stirred at 100 o C under N2 for 16 hours. The resulting mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether=30% v/v) to obtain the target compound 6.2 as solid (2.4 g, yield 72.2%). LC-MS (ESI) m/z: 296[M+H] + . Step 2: Synthesis of 2-(4-(trifluoromethyl)phenylamino)benzohydrazide (Compound 6.3) [00303] To the solution of methyl 2-(4-(trifluoromethyl)phenylamino)benzoate (2.3 g, 7.8 mmol) in EtOH (30 mL) was added N 2 H 4 ·H 2 O (0.39 g, 7.8 mmol). The mixture was stirred at 85 o C under N2 for 16 hours, concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether=30% v/v) to obtain the target compound 6.3 as oil (2 g, yield 83.3%). LC-MS (ESI) m/z: 296[M+H] + . Step 3: Synthesis of 5-(2-(4-(trifluoromethyl)phenylamino)phenyl)-1,3,4-oxadiazol -2- amine (Compound 6.4) [00304] To the solution of 2-(4-(trifluoromethyl)phenylamino)benzohydrazide (1.9 g, 6.4 mmol) in 1,4-dioxane (10 mL) and H 2 O (10 mL) was added BrCN (0.68 g, 6.4 mmol) and NaHCO 3 (0.54 g, 6.4 mmol). The resulting mixture was stirred at rt under N2 for 16 hours, concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether=30% v/v) to obtain the target compound 6.4 as solid (800 mg, yield 38.8%). LC-MS (ESI) m/z: 321[M+H] + . Step 4: Synthesis of N-(5-(2-(4-(trifluoromethyl)phenylamino)phenyl)-1,3,4-oxadia zol-2- yl)acrylamide (Compound A-2) [00305] To the solution of 5-(2-(4-(trifluoromethyl)phenylamino)phenyl)-1,3,4-oxadiazol - 2-amine (700 mg, 2.19 mmol) and Et 3 N (442 mg, 4.38 mmol) in THF (10 mL) was added acryloyl chloride (196 mg, 2.19 mmol). The mixture was stirred at 0 o C for 1 hour, concentrated and purified by prep-HPLC (MeCN/TFA/H 2 O) to obtain the target compound A-2 as solid (35 mg, yield 3.7%). LC-MS (ESI) m/z: 375[M+H] + . 1 H-NMR (400 MHz, DMSO-d6) δ (ppm) 12.12 (s, 1H), 9.16 (s, 1H), 7.82 (dd, J = 7.9, 1.4 Hz, 1H), 7.65 (d, J = 8.5 Hz, 2H), 7.60 – 7.49 (m, 2H), 7.39 (d, J = 8.5 Hz, 2H), 7.14 (t, J = 7.5 Hz, 1H), 6.46 (qd, J = 17.0, 5.8 Hz, 2H), 5.95 (dd, J = 9.9, 1.9 Hz, 1H). Scheme 7. Synthesis of A-3 Step 1: Synthesis of 5-nitro-2-(4-(trifluoromethyl)phenoxy)benzonitrile (Compound 7.3) [00306] The mixture of 2-fluoro-5-nitrobenzonitrile (1 g, 6.02 mmol), 4-(trifluoromethyl) phenol (0.976 g, 6.02 mmol) and Na2CO 3 (0.83mg, 12.04 mmol) in DMAc (20 mL) was stirred at 100 o C for 16 hours. The mixture was diluted with water (100 mL) and extracted with EtOAc (100 mL x 3), the combined organics were washed with brine (100 mL), dried over anhydrous Na2SO 4 , filtered and concentrated to obtain the target compound 7.3 as solid (1.7 g, yield 91.6%). LC-MS (ESI) m/z: No mass. 1 H-NMR (400 MHz, DMSO-d6) δ (ppm): 8.93 (dd, J = 9.2, 2.9 Hz, 1H), 8.46 (dd, J = 9.3, 2.8 Hz, 1H), 7.93 (d, J = 8.6 Hz, 2H), 7.56 (t, J = 7.1 Hz, 2H), 7.21 (t, J = 9.8 Hz, 1H). Step 2: Synthesis of 5-(5-nitro-2-(4-(trifluoromethyl)phenoxy)phenyl)-2H-tetrazol e (Compound 7.4) [00307] To the solution of 5-nitro-2-(4-(trifluoromethyl)phenoxy)benzonitrile (1.6 g, 5.2 mmol) in 1,4-dioxane (20 mL) and H 2 O (10 mL) was added NaN 3 (0.67 g, 10.4 mmol) and ZnBr 2 (0.58 g, 2.6 mmol). The mixture was stirred at 100 o C for16 hours, concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether=30% v/v) to obtain the target compound 7.4 as solid (500 mg, yield 27.4%). LC-MS (ESI) m/z: 352[M+H] + . Step 3 Synthesis of 2-methyl-5-(5-nitro-2-(4-(trifluoromethyl)phenoxy)phenyl)-2H - tetrazole (Compound 7.5) [00308] To the solution of 5-(5-nitro-2-(4-(trifluoromethyl)phenoxy)phenyl)-2H-tetrazol e (400 mg, 1.14 mmol) in DMF (10 mL) was added NaH (91.2 mg, 2.28 mmol), the mixture was stirred at 0 o C under N2 for 0.5 hour, and then CH3I (160 mg, 1.14 mmol) was added. The resulting mixture was stirred at rt for 1 hour, concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 30% v/v) to obtain the target compound 7.5 as solid (100 mg, yield 24.0%). LC-MS (ESI) m/z: 366[M+H] + . Step 4: Synthesis of 3-(2-methyl-2H-tetrazol-5-yl)-4-(4-(trifluoromethyl)phenoxy) aniline (Compound 7.6) [00309] To a solution of 2-methyl-5-(5-nitro-2-(4-(trifluoromethyl)phenoxy)phenyl)-2H - tetrazole (80 mg, 0.22 mmol) in EtOH (10 mL) and THF (10 mL) was added Raney nickel (9 mg, 0.022 mmol), and then N2H4·H 2 O (11 mg, 0.22 mmol) was added. The mixture was stirred at rt for 1 hour, filtered and concentrated in vacuum, the residue was purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether=30% v/v) to obtain the target compound 7.6 as oil (50 mg, yield 54.5%). LC-MS (ESI) m/z: 336[M+H] + . Step 5: Synthesis of N-(3-(2-methyl-2H-tetrazol-5-yl)-4-(4- (trifluoromethyl)phenoxy)phenyl)acrylamide (Compound A-3) [00310] To a solution of 3-(2-methyl-2H-tetrazol-5-yl)-4-(4- (trifluoromethyl)phenoxy)aniline (50 mg, 0.15 mmol) in THF (10 mL) was added Et3N (31 mg, 0.30 mmol) and acryloyl chloride (14 mg, 0.15 mmol), the mixture was stirred at 0 o C for 1 hour, concentrated and purified by prep-HPLC (MeCN/H 2 O/TFA) to obtain the target compound A-3 as solid (4.5 mg, yield 7.7%). LC-MS (ESI) m/z: 390[M+H] + .1H-NMR (400 MHz, DMSO-d6) δ (ppm): 8.45 (d, J = 2.4 Hz, 1H), 7.91 (dd, J = 8.8, 2.6 Hz, 1H), 7.60 (d, J = 8.6 Hz, 2H), 7.24 (d, J = 8.8 Hz, 1H), 7.04 (d, J = 8.6 Hz, 2H), 6.51 – 6.40 (m, 2H), 5.84 (dd, J = 9.3, 2.3 Hz, 1H), 4.61 (s, 1H), 4.34 (s, 3H). Scheme 8. Synthesis of A-4 Step 1: Synthesis of 2-(cyclohexylamino)-5-nitrobenzoic acid (Compound 8.3) [00311] The mixture of 2-fluoro-5-nitrobenzoic acid (1000 mg, 5.4 mmol) and cyclohexanamine (535 mg, 5.4 mmol) in pyridine (20 mL) was stirred at 60 o C for 16 hours. The mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether=50% v/v) to obtain the target compound 8.3 as solid (1 g, yield 70.0%). LC-MS (ESI) m/z: 265[M+H] + . Step 2: Synthesis of 2-(cyclohexylamino)-5-nitrobenzohydrazide (Compound 8.4) [00312] To the solution of 2-(cyclohexylamino)-5-nitrobenzoic acid (1 g, 3.79 mmol) in EtOH (30 mL) was added H 2 SO 4 (30 mL), the mixture was stirred at 100 o C for 16 hours. The solvent was removed, ammonia solution (30 mL) was added to the residue to render the resulting solution strongly alkaline. The mixture was extracted with ether (100 mL), the organic was dried over anhydrous Na2SO 4 , filtered and concentrated inn vacuum. N2H4H 2 O (1 mL) was added to the residue and the resulting mixture was stirred at 120 o C for 3 hours. The mixture was diluted with water (100 mL) and extracted with EtOAc (3 x 50 mL), the combined organics were washed with brine (100 mL), dried over anhydrous Na2SO 4 , concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether=50% v/v) to obtain the target compound 8.4 as oil (300 mg, yield 28.5%). LC-MS (ESI) m/z: 279[M+H] + . Step 3: Synthesis of N-cyclohexyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-4-nitroanilin e (Compound 8.6) [00313] The mixture of 2-(cyclohexylamino)-5-nitrobenzohydrazide (300 mg, 1.08 mmol) and 1,1,1-triethoxyethane (175 mg, 1.08 mmol) in 1,4-dioxane (10 mL) was stirred at 110 o C for 16 hours. The mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether=50% v/v) to obtain the target compound 8.6 as solid (250 mg, yield 76.7%). LC-MS (ESI) m/z: 303[M+H] + . Step 4: Synthesis of N1-cyclohexyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)benzene-1,4- diamine (Compound 8.7) [00314] To a solution of N-cyclohexyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-4-nitroanilin e (250 mg, 0.83 mmol) in EtOH (10 mL) and THF (10 mL) was added Raney nickel (33 mg, 0.08 mmol), and then N2H4·H 2 O (41 mg, 0.83 mmol) was added. The mixture was stirred at rt for 1 hour and filtered through celite, the filtrate was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether=50% v/v) to obtain the target compound 8.7 as oil (200 mg, yield 89.3%). LC-MS (ESI) m/z: 273[M+H] + . Step 5: Synthesis of N-(4-(cyclohexylamino)-3-(5-methyl-1,3,4-oxadiazol-2- yl)phenyl)propionamide (Compound A-4) [00315] To a solution of N1-cyclohexyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)benzene-1,4- diamine (180 mg, 0.66 mmol) and Et3N (133 mg, 1.32 mmol) in THF (10 mL) was added propionyl chloride (61 mg, 0.66 mmol). The mixture was stirred at 0 o C for 1 hour, concentrated and purified by prep-HPLC (MeCN/TFA/H 2 O to obtain the target compound A- 4 as solid (64 mg, yield 29.4%). LC-MS (ESI) m/z: 329[M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ (ppm): 9.70 (s, 1H), 8.12 (d, J = 2.5 Hz, 1H), 7.47 (dd, J = 9.1, 2.5 Hz, 1H), 7.26 (d, J = 7.7 Hz, 1H), 6.87 (d, J = 9.2 Hz, 1H), 3.52 (d, J = 7.9 Hz, 1H), 2.58 (s, 3H), 2.27 (q, J = 7.6 Hz, 2H), 1.97 (d, J = 9.3 Hz, 2H), 1.76 – 1.65 (m, 2H), 1.57 (s, 1H), 1.42 (dd, J = 22.4, 11.7 Hz, 2H), 1.36 – 1.26 (m, 3H), 1.08 (t, J = 7.6 Hz, 3H). Scheme 9. Synthesis of A-5 Step 1: Synthesis of 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxabo rolane (Compound 9.3) [00316] To a solution of 2-bromo-1-fluoro-4-nitrobenzene (1000 mg, 4.6 mmol) in 1,4- dioxane (25 ml) and DMSO (0.5 mL) was added 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2- dioxaborolane) (1280 mg, 5.0 mmol), KOAc (900 mg, 9.2 mmol) and Pd(dppf)Cl2 (168 mg, 0.22 mmol). The mixture was stirred at 90 o C under N 2 for 16 hours, concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether=50% v/v) to obtain the target compound 9.3 as oil (800 mg, yield 65.3%). LC-MS (ESI) m/z: 268[M+H] + . Step 2: Synthesis of 2-(2-fluoro-5-nitrophenyl)pyrimidine (Compound 9.5) [00317] To a solution of 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane (800 mg, 3.00 mmol) in Me 2 CHOH (5 ml), PhMe (5 mL) and H 2 O (5 mL) was added 2-bromopyrimidine (473 mg, 3.00 mmol), K3PO 4 (1908 mg, 9.00 mmol) and Pd(dppf)Cl2 (110 mg, 0.15 mmol). The mixture was stirred at 85 o C under N2 for 4 hours. The mixture was diluted with water (100 mL) and extracted with EtOAc (3x50 mL), the combined organics were washed with brine (100 mL), dried over anhydrous Na2SO 4 , concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether=50% v/v) to obtain the target compound 9.5 as solid (600 mg, yield 91.4%). LC-MS (ESI) m/z: 220[M+H] + . Step 3: Synthesis of N-(4,4-difluorocyclohexyl)-4-nitro-2-(pyrimidin-2-yl)aniline (Compound 9.7) [00318] To a solution of 2-(2-fluoro-5-nitrophenyl)pyrimidine (513 mg, 2.17 mmol) in ACN (20 mL) was added N-(4,4-difluorocyclohexyl)-4-nitro-2-(pyrimidin-2-yl)aniline (450 mg, 1.98 mmol) and Et3N (603 mg, 5.94 mmol), the mixture was stirred at 85 o C under N2 for 16 hours. The mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether=50% v/v) to obtain the target compound 9.7 as solid (300 mg, yield 49.1%). LC-MS (ESI) m/z: 335[M+H] + . Step 4: Synthesis of N1-(4,4-difluorocyclohexyl)-2-(pyrimidin-2-yl)benzene-1,4-di amine (Compound 9.8) [00319] To the solution of N-(4,4-difluorocyclohexyl)-4-nitro-2-(pyrimidin-2-yl)aniline (250 mg, 0.75 mmol) in EtOH (10 mL) and THF (10 mL) was added Raney nickel (40 mg, 0.07 mmol), and then N 2 H 4 ·H 2 O (35 mg, 0.75 mmol) was added. The mixture was stirred at rt for 1 hour, concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether=50% v/v) to obtain the target compound 9.8 as oil (200 mg, yield 88.1%). LC-MS (ESI) m/z: 305[M+H] + . Step 5: Synthesis of N-(4-(4,4-difluorocyclohexylamino)-3-(pyrimidin-2- yl)phenyl)acrylamide (Compound A-5) [00320] To the solution of N1-(4,4-difluorocyclohexyl)-2-(pyrimidin-2-yl)benzene-1,4- diamine (180 mg, 0.59 mmol) and Et3N (119 mg, 1.18 mmol) in THF (10 mL) was added acryloyl chloride (53 mg, 0.59 mmol). The mixture was stirred at 0 o C for 1 hour, concentrated and purified by prep-HPLC (MeCN/TFA/H 2 O) to obtain the target compound A-5 as solid (49 mg, yield 23.2%). LC-MS (ESI) m/z: 359[M+H] + . 1 H NMR (400 MHz, DMSO-d6) δ (ppm): 9.99 (s, 1H), 9.02 (d, J = 7.8 Hz, 1H), 8.90 (d, J = 4.9 Hz, 2H), 8.69 (d, J = 2.6 Hz, 1H), 7.75 (dd, J = 9.1, 2.3 Hz, 1H), 7.38 (t, J = 4.9 Hz, 1H), 6.88 (d, J = 9.1 Hz, 1H), 6.41 (dd, J = 17.0, 10.1 Hz, 1H), 6.21 (dd, J = 17.0, 2.0 Hz, 1H), 5.69 (dd, J = 10.1, 2.1 Hz, 1H), 3.75 (s, 1H), 2.05 (dd, J = 15.6, 5.9 Hz, 6H), 1.60 (d, J = 8.2 Hz, 2H). Scheme 10. Synthesis of A-6 Step 1: Synthesis of 2-bromo-4-nitro-N-(4-(trifluoromethyl)phenyl)aniline (Compound 10.3) [00321] To the solution of 4-(trifluoromethyl)aniline (11.0 g, 50.0 mmol) in DMAc (150.0 mL) was added NaH (60%, 4 g, 100.0 mmol). The resulting mixture was stirred at 0°C for 30 minutes, and then 2-bromo-1-fluoro-4-nitrobenzene (8.055 g, 50.0 mmol) was added. The mixture was stirred at 130°C for 16 hours. The reaction mixture was cooled down to room temperature, diluted with H 2 O (200 mL) and extracted with EtOAc (3 x 200 mL), the combined organic layer was dried over anhydrous Na 2 SO 4 , concentrated and purified by flash column chromatography on silica gel (eluting with 30% EA in PE) to afford the desired product 3 (2.431 g, 13.5% yield) as a yellow solid. LC-MS (ESI) m/z: 361 [M + H] + . Step 2: Synthesis of 2-bromo-N-(4-(trifluoromethyl)phenyl)benzene-1,4-diamine (Compound 10.4) [00322] The mixture of compound 10.3 (2.431 g, 6.73 mmol), Fe power (3.769 g, 67.3 mmol) and NH 4 Cl (1.740 g, 33.65 mmol) in EtOH (50.0 mL) and H 2 O (5.0 mL) was stirred at 90°C for 2 hours. After the completion of the reaction, the mixture was filtered, the filtrate was concentrated and purified by flash column chromatography on silica gel (eluting with 30% EA in PE) to afford the desired product 4 (2.197 g, 98.6% yield) as a brown solid. LC- MS (ESI) m/z: 331 [M + H] + . Step 3: Synthesis of 2-chloro-4-(oxetan-3-yloxy)pyrimidine (Compound 10.6) [00323] To a three necked flask was added compound 10.4 (4.0 g, 12.12 mmol) and 1,4- dioxane (80 mL), followed by 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (3.3858 g, 13.33 mmol), Pd(dppf)Cl2∙CH 2 Cl2 (494.9 mg, 0.606 mmol) and KOAc (2.3789 g, 24.24 mmol). The flask was evacuated, and refilled with N 2 for three times. The resulting mixture was stirred at 100 o C for 2 hours and monitored by LC-MS. After the completion of the reaction, the mixture was concentrated and purified by flash column chromatography on silica gel (eluting with 30% EA in PE) to afford the desired product (3.5 g, 76% yield) as a brown solid. LC-MS (ESI) m/z: 379 [M + H] + . Step 4: Synthesis of 2-bromo-N-(4-(trifluoromethyl)phenyl)benzene-1,4-diamine (Compound 10.10) [00324] To the mixture of 2,4-dichloropyrimidine (2.235 g, 15.0 mmol) and oxetan-3-ol (1.112 g, 15.0 mmol) in THF (100.0 mL) was added t-BuOK (3.366 g, 30.0 mmol). The resulting mixture was stirred at room temperature for 16 hours and monitored by LC-MS. After the completion of the reaction, the mixture was concentrated and purified by flash column chromatography on silica gel (eluting with 30% EA in PE) to afford the desired product (2.309 g, 82.8% yield) as a white solid. LC-MS (ESI) m/z: 187 [M + H] + . Step 5: Synthesis of 2-(4-(oxetan-3-yloxy)pyrimidin-2-yl)-N1-(4- (trifluoromethyl)phenyl)benzene-1,4-diamine (Compound 10.11) [00325] To a three necked flask was added compound 10.6 (1.512g, 4.0 mmol), 1,4- dioxane (20 mL) and H 2 O (2.0 mL), followed by the addition of compound 10.10 (781.2 mg, 4.2 mmol), Pd(dppf)Cl2∙CH 2 Cl2 (163.3 mg, 0.2 mmol) and Na2CO 3 (864.0 mg, 8.0 mmol). The flask was evacuated, and refilled with N 2 for three times. The resulting mixture was stirred at 100 o C for 2 hours and monitored by LC-MS. the mixture was concentrated and purified by flash column chromatography on silica gel (eluting with 1% MeOH in DCM) to afford the desired product 11 (210 mg, 13.1% yield) as a yellow solid. LC-MS (ESI) m/z: 403 [M + H] + . Step 6: Synthesis of N-(3-(4-(oxetan-3-yloxy)pyrimidin-2-yl)-4-((4- (trifluoromethyl)phenyl)amino)phenyl)acrylamide (Compound A-6) [00326] To the solution of compound 10.11 (200.0 mg, 0.5 mmol) and Et3N (101.2 mg, 1.0 mmol) in DCM (5.0 mL) was added acryloyl chloride (45.3 mg, 0.5 mmol) dropwise at 0°C. The resulting solution was stirred at 0°C for 20 min and monitored by LC-MS. The solvent was removed under reduce pressure to leave the crude product, which was purified by flash column chromatography on silica gel (eluting with 1% MeOH in DCM) to afford the desired product A-6 (135.0 mg, 59.2% yield) as a light yellow solid. LC-MS (ESI) m/z: 457 [M+H] + . NMR (400 MHz, DMSO-d 6 ) δ (ppm): 10.79 (s, 1H), 10.24 (s, 1H), 8.74 – 8.72 (m, 2H), 7.72 (dd, J = 8.8, 2.4 Hz, 1H), 7.58 (d, J = 8.4 Hz, 2H), 7.49 (d, J = 8.8 Hz, 1H), 7.31 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 5.6 Hz, 1H), 6.48 (dd, J = 16.8, 10.0 Hz, 1H), 6.29 (dd, J = 17.2, 2.0 Hz, 1H), 5.78 (dd, J = 10.0, 2.0 Hz, 1H), 5.74 – 5.67 (m, 1H), 5.05 (t, J = 7.2 Hz, 2H), 4.67 (dd, J = 7.6, 5.6 Hz, 2H). 19 F NMR (376 MHz, DMSO-d6) δ (ppm): -59.75 Scheme 11. Synthesis of A-7 Step 1: Synthesis of 1-(2-chloropyrimidin-4-yl)pyrrolidin-3-ol (Compound 11.3) [00327] A mixture of 2,4-dichloropyrimidine (500 mg, 3.4 mmol), pyrrolidin-3-ol (290 mg, 3.4 mmol) and Et 3 N (690 mg, 6.8 mmol) in DCM (10 mL) was stirred at RT under N 2 for 16 hours. The mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether=50% v/v) to obtain the target compound 11.3 as solid (400 mg, yield 59.1%). LC-MS (ESI) m/z: 199[M+H] + . Step 2: Synthesis of 1-(2-(5-amino-2-(4- (trifluoromethyl)phenylamino)phenyl)pyrimidin-4-yl)pyrrolidi n-3-ol (Compound 11.5) [00328] A mixture of 1-(2-chloropyrimidin-4-yl)pyrrolidin-3-ol (70 mg, 0.35 mmol), 2- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N1-(4-(trifluo romethyl)phenyl)benzene-1,4- diamine (130 mg, 0.35 mmol), Na 2 CO 3 (111 mg, 1.05 mmol) and Pd(dppf)Cl 2 (30 mg, 0.04 mmol) in H 2 O (1 mL) and 1,4-dioxane (10 mL) was stirred at 100 o C under N2 for 1 hour. The mixture was concentrated and purified by flash column chromatography on silica gel (MeOH in DCM =15% v/v) to obtain the target compound 11.5 as solid (100 mg, yield 68.9%). LC-MS (ESI) m/z: 415[M+H] + . Step 3: Synthesis of N-(3-(4-(3-hydroxypyrrolidin-1-yl)pyrimidin-2-yl)-4-(4- (trifluoromethyl)phenylamino)phenyl)acrylamide (A-7) [00329] To a solution of 1-(2-(5-amino-2-(4- (trifluoromethyl)phenylamino)phenyl)pyrimidin-4-yl)pyrrolidi n-3-ol (90 mg, 0.22 mmol) in THF (10 mL) was added acryloyl chloride (20 mg, 0.22 mmol) and Et 3 N (45 mg, 0.44 mmol). The mixture was stirred at 0 o C under N2 for 1 hour, concentrated and purified by prep-HPLC to obtain the target compound A-7 as solid (20 mg, yield 19.4%). LC-MS (ESI) m/z: 469[M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ (ppm): 10.77 (s, 1H), 10.23 (s, 1H), 8.80 – 8.69 (m, 2H), 7.72 (dd, J = 8.9, 2.5 Hz, 1H), 7.54 (dd, J = 35.3, 8.7 Hz, 3H), 7.30 (d, J = 8.5 Hz, 2H), 7.00 (d, J = 5.8 Hz, 1H), 6.47 (dd, J = 17.0, 10.1 Hz, 1H), 6.29 (dd, J = 17.0, 1.8 Hz, 1H), 5.83 – 5.63 (m, 2H), 5.05 (t, J = 7.1 Hz, 2H), 4.76 – 4.58 (m, 2H). Scheme 12. Synthesis of A-8 Step 1: Synthesis of 2-(pyrimidin-2-yl)-N1-(4-(trifluoromethyl)phenyl)benzene-1,4 - diamine (Compound 12.3) [00330] To a three necked flask was added compound 12.1 (45.6 mg, 0.40 mmol), 1,4- dioxane (5.0 mL) and H 2 O (1.0 mL), followed by 2-chloropyrimidine (151.2 mg, 0.40 mmol), Pd(dppf)Cl 2 ∙CH 2 Cl 2 (40.8 mg, 0.02 mmol) and Na 2 CO 3 (84.8 mg, 0.8 mmol). The flask was evacuated, and refilled with N2 for three times. The resulting mixture was stirred at 100°C under N2 for 16 hours. After the completion of the reaction, the mixture was concentrated and purified by column chromatography on silica gel (eluting with 5% MeOH in DCM) to afford the desired product (50 mg, 37.8% yield) as a brown solid. LC-MS (ESI) m/z: 331 [M + H] + . Step 2: Synthesis of (E)-4-bromo-N-(3-(pyrimidin-2-yl)-4-((4- (trifluoromethyl)phenyl)amino)phenyl)but-2-enamide (Compound 12.5) [00331] To the solution of compound 12.3 (33.0 mg, 0.10 mmol) and Et3N (12.9 mg, 0.11 mmol) in DCM (2.0 mL) was added (E)-4-bromobut-2-enoyl chloride (12.9 mg, 0.10 mmol, prepared by stirring of 1.0 equiv of (E)-4-bromobut-2-enoic acid and 2.0 equiv oxalyl chloride in DCM at 50°C for 2 hours). The mixture was stirred at room temperature for 1 hour, concentrated and purified by column chromatography on silica gel (eluting with 2% MeOH in DCM) to give the desired product (34 mg, 71.4% yield) as a brown solid. LC-MS (ESI) m/z: 477 [M + H] + . Step 3: Synthesis of (E)-4-(dimethylamino)-N-(3-(pyrimidin-2-yl)-4-((4- (trifluoromethyl)phenyl)amino)phenyl)but-2-enamide (A-8) [00332] A mixture of compound 12.5 (24.0 mg, 0.021 mmol), dimethylamine (2M in THF, 100 uL, 0.20 mmol) and Na2CO 3 (10.6 mg, 0.10 mmol) in DCM (2.0 mL) was stirred at 0°C for 2 hours. The mixture was concentrated and purified by prep-HPLC to afford the desired product A-8 (1.6 mg, 7.3% yield) as a viscous liquid. LC-MS (ESI) m/z: 442 [M + H] + , 1 H NMR (400 MHz, CD3OD) δ (ppm): 8.82 (d, J = 4.9 Hz, 2H), 8.62 (d, J = 2.5 Hz, 1H), 7.68 (dd, J = 8.9, 2.5 Hz, 1H), 7.44 (dd, J = 8.7, 2.9 Hz, 3H), 7.28 (t, J = 4.9 Hz, 1H), 7.22 (d, J = 8.4 Hz, 2H), 6.80 – 6.71 (m, 1H), 6.48 (d, J = 15.4 Hz, 1H), 3.91 (d, J = 7.1 Hz, 2H), 2.85 (s, 6H). 19 F NMR (376 MHz, CD3OD) δ (ppm): -63.08, -76.99. Scheme 13. Synthesis of A-9 Step 1: Synthesis of 2-chloro-5-(oxetan-3-yloxy)pyrimidine (Compound 13.3) [00333] To a solution of oxetan-3-ol (0.55 g, 7.43 mmol) in DMF (10 mL) was added NaH (60%, 0.54 g, 13.52 mmol), the mixture was stirred at 0 o C under N 2 for 0.5 hour, and then 2,5-dichloropyrimidine (1 g, 6.76 mmol) was added. The resulting mixture was stirred at RT for 16 hours, diluted with water (100 mL) and extracted with EtOAc (50 mL x 3), the combined organic was dried over anhydrous Na 2 SO 4 , concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether=50% v/v) to obtain the target compound 13.3 as oil (1.2 g, yield 95%). LC-MS (ESI) m/z: 186[M+H] + . Step 2: Synthesis of 2-(5-(oxetan-3-yloxy)pyrimidin-2-yl)-N1-(4- (trifluoromethyl)phenyl)benzene-1,4-diamine (Compound 13.5) [00334] A mixture of 2-chloro-5-(oxetan-3-yloxy)pyrimidine (150 mg, 0.80 mmol), 2- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N1-(4-(trifluo romethyl)phenyl)benzene-1,4- diamine (300 mg, 0.80 mmol), Na2CO 3 (255 mg, 2.4 mmol) and Pd(dppf)Cl2 (59 mg, 0.08 mmol) in H 2 O (1 mL) and 1,4-dioxane (10 mL) was stirred at 100 o C under N2 for 1 hour. The mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether =15% v/v) to obtain the target compound 13.5 as solid (100 mg, yield 31.1%). LC-MS (ESI) m/z: 402[M+H] + . Step 3: Synthesis of N-(3-(5-(oxetan-3-yloxy)pyrimidin-2-yl)-4-(4- (trifluoromethyl)phenylamino)phenyl)acrylamide (Compound A-9) [00335] To a solution of 2-(5-(oxetan-3-yloxy)pyrimidin-2-yl)-N1-(4- (trifluoromethyl)phenyl)benzene-1,4-diamine (90 mg, 0.23 mmol) in THF (10 mL) was added acryloyl chloride (21 mg, 0.23 mmol) and Et3N (47 mg, 0.46 mmol). The mixture was stirred at 0 o C under N 2 for 1 hour, concentrated and purified by prep-HPLC to obtain the target compound A-9 as solid (2 mg, yield 2%). LC-MS (ESI) m/z: 456[M+H] + . 1 H NMR (400 MHz, DMSO-d6) δ (ppm): 10.31 (s, 1H), 8.58 (s, 2H), 8.16 (s, 1H), 7.83-7.67 (m, 2H), 7.37 (dd, J = 11.9, 8.7Hz, 3H), 6.74 (d, J = 8.5 Hz, 2H), 6.45 (dd, J = 16.9, 10.2 Hz, 1H), 6.27 (d, J = 16.9 Hz, 1H), 5.78 (d, J = 11.8 Hz, 1H), 5.55 (t, J = 5.6 Hz, 1H), 4.88 (t, J = 6.9 Hz, 2H),4.66 – 4.52 (m, 2H). Scheme 14. Synthesis of A-10 Step 1: Synthesis of 2-bromo-4-nitro-1-((4-(trifluoromethyl)benzyl)oxy)benzene (Compound 14.3) [00336] A mixture of 2-bromo-4-nitrophenol (4.36, 20.0 mmol), 1-(bromomethyl)-4- (trifluoromethyl)benzene (5.00 g, 21 mmol) and K 2 CO 3 (5.52 mg, 40.0 mmol) in acetone (10.0 mL) was stirred at 50°C for 3 hours. After the completion of the reaction, the mixture was filtered, the filter cake was washed with cooled H 2 O and EtOH, and dried under vacuum to afford the desired product as solid (7.1 g, 94.7%), which was used directly for the next step without further purification. LC-MS (ESI) m/z: 376 [M + H] + . Step 2: Synthesis of 4,4,5,5-tetramethyl-2-(5-nitro-2-((4- (trifluoromethyl)benzyl)oxy)phenyl)-1,3,2-dioxaborolane (Compound 14.5) [00337] To a three necked flask was added compound 14.3 (3.0 g, 8.0 mmol) and 1,4- dioxane (60.0 mL), followed by f 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (2.134 g, 8.4 mmol), Pd(dppf)Cl2∙CH 2 Cl2 (327 mg, 0.40 mmol) and KOAc (1.568 g, 16.0. mmol). The flask was evacuated, and refilled with N 2 for three times. The resulting mixture was stirred at 100°C under N 2 for 16 hours. After the completion of the reaction, the solvents were removed under reduce pressure to leave the crude product, which was purified by column chromatography on silica gel (eluting with 20% EtOAc in PE) to give the desired product (2.865 g, 84.7% yield) as a brown solid. LC-MS (ESI) m/z: 424 [M + H] + . Step 3: Synthesis of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-((4- (trifluoromethyl)benzyl)oxy)aniline (Compound 14.6) [00338] To the solution of compound 14.5 (846 mg, 2.0 mmol) and NH4Cl (535 mg, 10.0 mmol) in EtOH (2.0 mL) and H 2 O (1.0 mL) was added Fe powder (1.12 g, 20 mmol). The resulting mixture was stirred at 90 o C for 2 hours. The mixture was filtered through celite, the filtrate was concentrated under reduce pressure to leave the crude compound 14.6, which was used directly for the next step without further purification. LC-MS (ESI) m/z: 393 [M + H] + . Step 4: Synthesis of 3-(pyrimidin-2-yl)-4-((4-(trifluoromethyl)benzyl)oxy)aniline (Compound 14.8) [00339] To a three necked flask was added compound 14.6 (500 mg, 1.27 mmol), 1,4- dioxane (10 mL) and H 2 O (2.0 mL), followed by 2-chloropyrimidine (152.8 mg, 1.34 mmol), Pd(dppf)Cl2∙CH 2 Cl2 (52.3 mg, 0.64 mmol) and Na2CO 3 (269.2 mg, 2.54 mmol). The flask was evacuated, and refilled with N2 for three times. The resulting mixture was stirred at 100 o C under N 2 for 16 hours. After the completion of the reaction, the solvents were removed under reduce pressure to leave the crude product, which was purified by column chromatography on silica gel (eluting with 5% MeOH in DCM) to afford the desired product (0.21 g, 46% yield) as a yellow solid. LC-MS (ESI) m/z: 346 [M + H] + . Step 5: Synthesis of N-(3-(pyrimidin-2-yl)-4-((4- (trifluoromethyl)benzyl)oxy)phenyl)acrylamide (Compound A-10) [00340] To the solution of compound 14.8 (150.0 mg, 0.382 mmol) and Et 3 N (77.2 mg, 0.764 mmol) in DCM (5.0 mL) was added acryloyl chloride (84.5 mg, 0.764 mmol). The mixture was stirred at 0°C for 2 hours and monitored by LC-MS. After the completion of the reaction the mixture was concentrated and purified by prep-HPLC to afford the desired pure product A-10 (45 mg, 30%) as a yellow solid. LC-MS (ESI) m/z: 346 [M + H] + . 1 H NMR (400 MHz, DMSO-d6) δ (ppm) 10.21 (s, 1H), 8.96 (d, J = 5.2 Hz, 2H), 8.04 (d, J = 2.6 Hz, 1H), 7.77-7.68 (m, 5H), 7.49 (t, J = 4.9 Hz, 1H), 7.21 (d, J = 8.8 Hz, 1H), 6.43 (dd, J = 16.8, 10.0 Hz, 1H), 6.25 (dd, J = 16.8, 2.0 Hz, 1H), 5.75 (dd, J = 10.0, 2.0 Hz, 1H), 5.28 (s, 2H). 19 F NMR (376 MHz, DMSO-d 6 ) δ (ppm): -60.87. Scheme 15. Synthesis of A-11 Step 1: Synthesis of 2-chloro-4-(methylsulfonyl)pyrimidine (Compound 15.2) [00341] To a solution of 2-chloro-4-(methylthio)pyrimidine (500 mg, 3.2 mmol) in DCM (100 mL) was added mCPBA (540 mg, 3.2 mmol). The mixture was stirred at RT under N2 for 16 hours. The mixture was washed with saturated NaHCO 3 solution (100 mL), dried over anhydrous Na 2 SO 4 , filtered and concentrated under vacuum to obtain the target compound 15.2 as solid (500 mg, yield 81%). LC-MS (ESI) m/z: 192[M+H] + . Step 2: Synthesis of 2-(2-chloropyrimidin-4-yloxy)ethanol (Compound 15.4) [00342] To a solution of 2-chloro-4-(methylsulfonyl)pyrimidine (450 mg, 2.34 mmol) in DMF (10 mL) was added ethane-1,2-diol (291 mg, 4.68 mmol) and K2CO 3 (496 mg, 4.68 mmol). The mixture was stirred at RT under N 2 for 2 hours. The mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 20% v/v) to obtain the target compound 15.4 as oil (200 mg, yield 49.2%). LC-MS (ESI) m/z: 174[M+H] + . Step 3: Synthesis of 2-(2-(5-amino-2-(4-(trifluoromethyl)phenylamino)phenyl) pyrimidin-4-yloxy)ethanol (Compound 15.6) [00343] The mixture of 2-(2-chloropyrimidin-4-yloxy)ethanol (200 mg, 0.5 mmol), 2- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N1-(4-(trifluo romethyl)phenyl)benzene-1,4- diamine (100 mg, 0.5 mmol), Na2CO3 (160 mg, 1.5 mmol) and Pd(dppf)Cl2 (40 mg, 0.05 mmol) in H 2 O (1 mL) and 1,4-dioxane (10 mL) was stirred at 100 o C under N 2 for 1 hour. The mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 20% v/v) to obtain the target compound 15.6 as solid (100 mg, yield 51.3%). LC-MS (ESI) m/z: 390[M+H] + . Step 4: Synthesis of N-(3-(4-(2-hydroxyethoxy)pyrimidin-2-yl)-4-(4-(trifluorometh yl) phenylamino)phenyl)acrylamide (Compound A-11) [00344] To a solution of 2-(2-(5-amino-2-(4-(trifluoromethyl)phenylamino)phenyl) pyrimidin-4-yloxy)ethanol (90 mg, 0.23 mmol) in THF (10 mL) was added acryloyl chloride (21 mg, 0.23 mmol) and Et3N (47 mg, 0.46 mmol). The mixture was stirred at 0 o C under N2 for 1 hour, concentrated and purified by prep-HPLC (MeCN/TFA/H 2 O) to obtain the target compound A-11 as solid (5 mg, yield 5%). LC-MS (ESI) m/z: 444[M+H] + . 1 H NMR (400 MHz, DMSO-d6) δ (ppm): 10.69 (s, 1H), 10.26 (s, 1H), 8.67 (dd, J = 8.1, 4.2 Hz, 2H), 8.41 (s, 1H), 7.86 (s, 1H), 7.57 (d, J = 8.6 Hz, 2H), 7.50 (d, J = 9.0 Hz, 1H), 7.29 (d, J = 8.5 Hz, 2H), 6.91 (d, J = 5.8 Hz, 1H), 6.46 (dd, J = 16.7, 9.7 Hz, 1H), 6.26 (d, J = 16.8 Hz, 1H), 5.76 (d, J = 12.1 Hz, 1H), 4.99 (s, 1H), 4.55 – 4.42 (m, 2H), 3.78 (s, 1H). Scheme 16. Synthesis of A-12 Step 1: Synthesis of 3-bromo-5-nitro-2-(4-(trifluoromethyl)phenoxy)pyridine (Compound 16.3) [00345] A mixture of 3-bromo-2-chloro-5-nitropyridine (1500 mg, 6.75 mmol), 4- (trifluoromethyl)phenol (1093 mg, 6.75 mmol) and Cs2CO 3 (2413 mg, 7.4 mmol) in DMSO (20 mL) was stirred at 120 o C under N2 overnight. The reaction mixture was cooled down to room temperature, diluted with H 2 O (200 mL) and extracted with ethyl acetate (300 mL x2), the combined organic was washed with water (500 mL), dried over anhydrous Na 2 SO 4 , filtered and concentrated to leave the crude product 3 as yellow solid (2 g, yield 82%). LC- MS (ESI) m/z: No Mass. Step 2: Synthesis of 5-bromo-6-(4-(trifluoromethyl)phenoxy)pyridin-3-amine (Compound 16.4) [00346] A mixture of compound 16.3 (1000 mg, 2.76 mmol), Fe (1546 mg, 27.6 mmol) and NH4Cl (1462 mg, 27.6 mmol) in EtOH (20 mL) was stirred at 70 o C under N2 for 5 hours. The reaction mixture was filtered, the filtrate was concentrated to leave the crude product 4 as yellow solid (800mg, yield 87%). LC-MS (ESI) m/z: 333[M+H] + . Step 3: Synthesis of 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(4- (trifluoromethyl)phenoxy)pyridin-3-amine (Compound 16.6) [00347] A mixture of compound 16.4 (200 mg, 0.6 mmol), 4,4,4',4',5,5,5',5'-octamethyl- 2,2'-bi(1,3,2-dioxaborolane) (228 mg, 0.9 mmol), KOAc (176 mg, 1.8 mmol) and Pd(dppf)Cl2 (44 mg, 0.06 mmol) in 1.4-dixoane (10 mL) was stirred at 90 o C under N2 overnight. The reaction mixture was filtered, the filtrate was concentrated to leave the crude compound 16.6 (200mg, yield 87%) as oil, which was used directly for next step without further purification. LC-MS (ESI) m/z: 381[M+H] + . Step 4: Synthesis of 5-(pyrimidin-2-yl)-6-(4-(trifluoromethyl)phenoxy)pyridin-3-a mine (Compound 16.8) [00348] A mixture of compound 16.6 (100 mg, 0.25 mmol), 2-bromopyrimidine (40 mg, 0.25 mmol), K 2 CO 3 (105 mg, 0.75 mmol) and Pd(dppf)Cl 2 (20 mg, 0.025 mmol) in 1,4- dixoane (5 mL) and H 2 O (1 mL) was stirred at 90 o C under N2 overnight. The reaction mixture was concentrated and purified by prep-HPLC to obtain compound 16.8 as white solid (50 mg, yield 60%). LC-MS (ESI) m/z: 333[M+H] + . Step 5: Synthesis of N-(5-(pyrimidin-2-yl)-6-(4-(trifluoromethyl)phenoxy)pyridin- 3- yl)acrylamide (Compound A-12) [00349] A mixture of compound 16.8 (40 mg, 0.12 mmol), acryloyl chloride (12 mg, 0.12 mmol) and TEA (24 mg, 0.24 mmol) in DCM (10 mL) was stirred at 0 o C for 2 hours. The mixture was concentrated and purified by prep-HPLC to obtain the desired A-12 as white solid (10 mg, yield 22%). LC-MS (ESI) m/z: 387[M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ (ppm): 8.90 (d, J = 5.0 Hz, 2H), 8.65 (dd, J = 60.5, 2.7 Hz, 2H), 7.65 (d, J = 8.5 Hz, 2H), 7.47 (t, J = 5.0 Hz, 1H), 7.23 (d, J = 8.5 Hz, 2H), 6.43 (t, J = 6.1 Hz, 2H), 5.83 (dd, J = 8.9, 2.9 Hz, 1H). Scheme 17. Synthesis of A-13 Step 1: Synthesis of 2-(pyridazin-3-yl)-N1-(4-(trifluoromethyl)phenyl)benzene-1,4 - diamine (Compound 17.3) [00350] To the solution of 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N1-(4- (trifluoromethyl)phenyl)benzene -1,4-diamine (200 mg, 0.5 mmol) in H 2 O (1 mL) and 1,4- dioxane (10 mL) was added 3-bromopyridazine (80 mg, 0.5 mmol), Na 2 CO 3 (160 mg, 1.5 mmol) and Pd(dppf)Cl2 (40 mg, 0.05 mmol). ). The mixture was stirred at 100 o C under N2 for 1 hour. After cooled down to rt the mixture was diluted with water (100 mL) and extracted with EtOAc (3 x 100 mL), the combined organics were washed with brine (100 mL), dried over anhydrous Na2SO 4 , concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether=50% v/v) to obtain the target compound 17.3 as solid (100 mg, yield 57.5%). LC-MS (ESI) m/z: 330[M+H] + . Step 2: Synthesis of N-(3-(pyridazin-3-yl)-4-(4-(trifluoromethyl)phenylamino)phen yl) acrylamide (Compound A-13) [00351] To the solution of 2-(pyridazin-3-yl)-N1-(4-(trifluoromethyl)phenyl) benzene-1,4- diamine (90 mg, 0.37 mmol) in THF (10 mL) was added Et3N (75 mg, 0.74 mmol) and acryloyl chloride (25 mg, 0.37 mmol), the mixture was stirred at 0 o C for 1 hour, concentrated and purified by prep-HPLC (MeCN/H 2 O/TFA) to obtain the target compound A-13 as solid (20 mg, yield 19.1%). LC-MS (ESI) m/z: 384[M+H] + . 1 H NMR (400 MHz, DMSO-d6) δ (ppm): 10.34 (s, 1H), 9.17 (dd, J = 4.9, 1.6 Hz, 1H), 8.75 (s, 1H), 8.11 (d, J = 2.4 Hz, 1H), 7.82 (ddd, J = 8.6, 4.4, 2.0 Hz, 2H), 7.69 (dd, J = 8.6, 4.9 Hz, 1H), 7.50 – 7.37 (m, 3H), 6.86 (d, J = 8.6 Hz, 2H), 6.45 (dd, J = 17.0, 10.1 Hz, 1H), 6.28 (dd, J = 17.0, 2.0 Hz, 1H), 5.78 (dd, J = 10.1, 1.9 Hz, 1H). Scheme 18. Synthesis of A-14 Step 1: Synthesis of 4-(5-amino-2-(4-(trifluoromethyl)phenylamino)phenyl)pyridin- 2(1H)-one (Compound 18.3) [00352] To the solution of 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N1-(4- (trifluoromethyl)phenyl)benzene-1,4-diamine (200 mg, 0.5 mmol) in H 2 O (1 mL) and 1,4- dioxane (10 mL) was added 4-bromopyridin-2(1H)-one (90 mg, 0.5 mmol), Na2CO 3 (160 mg, 1.5 mmol) and Pd(dppf)Cl 2 (40 mg, 0.05 mmol). The mixture was stirred at 100 oC under N 2 for 1 hour. After cooled down to rt the mixture was diluted with water (100 mL) and extracted with EtOAc (3x100 mL), the combined organics were washed with brine (100 mL), dried over anhydrous Na2SO 4 , concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether=50% v/v) to obtain the target compound 18.3 as solid (100 mg, yield 54.8%). LC-MS (ESI) m/z: 345[M+H] + . Step 2: Synthesis of N-(3-(2-oxo-1,2-dihydropyridin-4-yl)-4-(4-(trifluoromethyl) phenylamino)phenyl)acrylamide (Compound A-14) [00353] To the solution of 4-(5-amino-2-(4-(trifluoromethyl)phenylamino)phenyl)pyridin- 2(1H)-one (90 mg, 0.26 mmol) in THF (10 mL) was added Et 3 N (53 mg, 0.52 mmol) and acryloyl chloride (24 mg, 0.26 mmol), the mixture was stirred at 0 o C for 1 hour, concentrated and purified by prep-HPLC (MeCN/H 2 O/TFA) to obtain the target compound A-14 as solid (33 mg, yield 31.7%). LC-MS (ESI) m/z: 399[M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ (ppm) 10.29 (s, 1H), 8.15 (s, 1H), 7.79 (d, J = 2.4 Hz, 1H), 7.70 (dd, J = 8.6, 2.4 Hz, 1H), 7.40 (d, J = 8.6 Hz, 2H), 7.33 (t, J = 7.7 Hz, 2H), 6.79 (d, J = 8.5 Hz, 2H), 6.44 (dd, J = 17.0, 10.1 Hz, 1H), 6.37 – 6.21 (m, 2H), 6.14 (dd, J = 6.8, 1.6 Hz, 1H), 5.78 (dd, J = 10.1, 2.0 Hz, 1H). Scheme 19. Synthesis of A-15 Step 1: Synthesis of 2-(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)-N 1-(4- (trifluoromethyl)phenyl)benzene-1,4-diamine (Compound 19.3) [00354] To a three necked flask was added compound 19.1 (756 mg, 2.0 mmol), 1,4- dioxane (40 mL) and H 2 O (10 mL), followed by the addition of 2-bromo-5-methyl-4,5,6,7- tetrahydrothiazolo[5,4-c]pyridine 2 (466 mg, 2.0 mmol), Pd(dppf)Cl 2 (72 mg, 0.1 mmol) and Na2CO 3 (426 mg, 4.0 mmol). The flask was evacuated, and refilled with N2 for three times. The resulting mixture was stirred at 100 o C for 2 hours and monitored by LC-MS. After the completion of the reaction, the solvents were removed under reduce pressure to leave the crude product, which was purified by column chromatography on silica gel (eluting with 1% MeOH in DCM) to afford the desired compound 19.3 (600 mg, 74.3% yield) as a yellow solid. LC-MS (ESI) m/z: 405 [M + H] + . Step 2: Synthesis of N-(3-(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl )-4-((4- (trifluoromethyl)phenyl)amino)phenyl)acrylamide (Compound A-15) [00355] To the solution of compound 19.3 (202.0 mg, 0.50 mmol) and Et 3 N (101.2 mg, 1.0 mmol) in DCM (15.0 mL) was added acryloyl chloride (45.2 mg, 0.50 mmol). The resulting mixture was stirred at 0°C for 20 minutes and monitored by LC-MS. After the completion of the reaction, the solvent was removed under reduce pressure to leave the crude product, which was purified by column chromatography on silica gel (eluting with 1% MeOH in DCM) to afford the desired product A-15 (52.0 mg, 22.7% yield) as a yellow solid. 1 H NMR (400 MHz, DMSO-d6) δ (ppm) 10.38 (s, 1H), 9.08 (s, 1H), 8.48 (d, J = 2.4 Hz, 1H), 7.83 (dd, J = 8.7, 2.4 Hz, 1H), 7.50 (d, J = 8.6 Hz, 2H), 7.39 (d, J = 8.7 Hz, 1H), 6.92 (d, J = 8.5 Hz, 2H), 6.46 (dd, J = 17.0, 10.1 Hz, 1H), 6.29 (dd, J = 17.0, 2.0 Hz, 1H), 5.79 (dd, J = 10.0, 2.0 Hz, 1H), 3.58 (s, 2H), 2.84 (t, J = 5.3 Hz, 2H), 2.73 (t, J = 5.6 Hz, 2H), 2.37 (s, 3H). 19 F NMR (376 MHz, DMSO-d 6 ) δ (ppm) -59.46. Scheme 20. Synthesis of A-16 Step 1: Synthesis of 2-(5-amino-2-((4-(trifluoromethyl)phenyl)amino)phenyl)-6,7- dihydrothiazolo[5,4-c]pyridin-4(5H)-one (Compound 20.3) [00356] To a solution of compound 20.1 (375.0 mg, 0.917 mmol) in 1,4-dioxane (8 mL) and H 2 O (2 mL) was added 2-bromo-6,7-dihydrothiazolo[5,4-c]pyridin-4(5H)-one (203.4 mg, 0.873 mmol), Pd(dppf)Cl2 (32.2 mg, 0.044 mmol) and Na2CO 3 (185.1 mg, 1.746 mmol). The flask was evacuated, and refilled with N2 for three times. The resulting mixture was stirred at 100 o C for 2 hours and monitored by LC-MS. After the completion of the reaction, the solvents were removed under reduce pressure to leave the crude product, which was purified by flash column chromatography on silica gel (eluting with 1% MeOH in DCM) to give the desired compound 20.3 (310 mg, 76.7% yield) as a yellow solid. LC-MS (ESI) m/z: 405 [M + H] + . Step 2: Synthesis of N-(3-(4-oxo-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)-4 -((4- (trifluoromethyl)phenyl)amino)phenyl)acrylamide (Compound A-16) [00357] To the solution of compound 20.3 (202.0 mg, 0.50 mmol) and Et3N (101.2 mg, 1.0 mmol) in DCM (15.0 mL) was added dropwise acryloyl chloride (45.2 mg, 0.50 mmol). The mixture was stirred at 0°C for 20 minutes and monitored by LC-MS. After the completion of the reaction, the solvent was removed under reduce pressure to leave the crude product, which was purified by column chromatography on silica gel (eluting with 1% MeOH in DCM) to give the desired product A-16 (56 mg, 24.5% yield) as a yellow solid. 1 H NMR (400 MHz, DMSO-d6) δ (ppm) 10.45 (s, 1H), 8.81 (s, 1H), 8.66 (d, J = 2.4 Hz, 1H), 7.93 (dd, J = 8.7, 2.5 Hz, 1H), 7.88 (s, 1H), 7.50 (d, J = 8.6 Hz, 2H), 7.41 (d, J = 8.7 Hz, 1H), 6.84 (d, J = 8.5 Hz, 2H), 6.47 (dd, J = 16.9, 10.1 Hz, 1H), 6.31 (dd, J = 17.0, 1.9 Hz, 1H), 5.80 (dd, J = 10.1, 1.9 Hz, 1H), 3.50 (td, J = 7.0, 2.4 Hz, 2H), 3.03 (t, J = 7.0 Hz, 2H). 19 F NMR (376 MHz, DMSO-d6) δ (ppm) -59.45. Scheme 21. Synthesis of A-17 Step 1: Synthesis of 2-(cyclohexylamino)-5-nitrobenzonitrile (Compound 21.3) [00358] The mixture of 2-fluoro-5-nitrobenzonitrile (1 g, 6.0 mmol), cyclohexanamine (0.6 g, 6.0 mmol) and TEA (1.2 g, 12.0 mmol) in DMAc (5 mL) was heated at 120 o C under N2 for 16 hours, until all starting material was consumed as showed by LCMS. The mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 50% v/v) to afford the target compound 21.3 as solid (1.4 g, yield 94.9%). LC-MS (ESI) m/z: 246 [M+H] + . Step 2: Synthesis of N-cyclohexyl-4-nitro-2-(2H-tetrazol-5-yl) aniline (Compound 21.4) [00359] The mixture of 2-(cyclohexylamino)-5-nitrobenzonitrile (1.3 g, 5.3 mmol) and NaN 3 (0.52 g, 7.9 mmol) in DMF (30 mL) was heated at 120 o C under N 2 for 16 hours, until all starting material was consumed as showed by LCMS. The mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 20% v/v) to obtain the target compound 21.4 as solid (800 mg, yield 52.3%). LC-MS (ESI) m/z: 289 [M+H] + . Step 3: Synthesis of N-cyclohexyl-2-(2-(2-fluorobenzyl)-2H-tetrazol-5-yl)-4-nitro aniline (Compound 21.6) [00360] The mixture of N-cyclohexyl-4-nitro-2-(2H-tetrazol-5-yl)aniline (700 mg, 2.43 mmol), 1-(bromomethyl)-2-fluorobenzene (456 mg, 2.43 mmol) and K2CO 3 (670 mg, 4.86 mmol) in DMF (20 mL) was stirred at rt under N 2 for 3 hours. The mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 40% v/v) to obtain the target compound 21.6 as solid (600 mg, yield 62.3%). LC-MS (ESI) m/z: 397 [M+H] + . Step 4: Synthesis of N1-cyclohexyl-2-(2-(2-fluorobenzyl)-2H-tetrazol-5-yl)benzene -1,4- diamine (Compound 21.7) [00361] To the solution of N-cyclohexyl-2-(2-(2-fluorobenzyl)-2H-tetrazol-5-yl)-4- nitroaniline (500 mg, 1.26 mmol) in EtOH (15 mL) and THF (15 mL) was added Raney nickel (53 mg, 0.13 mmol), and then N2H4·H 2 O (63 mg, 1.26 mmol) was added. The mixture was stirred at rt for 1 hour and filtered, the filtrate was concentrated under reduced pressure to leave the crude compound 21.7 as oil (400 mg, yield 86.5%). LC-MS (ESI) m/z: 367 [M+H] + . Step 5: Synthesis of N-(4-(cyclohexylamino)-3-(2-(2-fluorobenzyl)-2H-tetrazol-5- yl)phenyl)acrylamide (Compound A-17) [00362] To the mixture of N1-cyclohexyl-2-(2-(2-fluorobenzyl)-2H-tetrazol-5-yl)benzene - 1,4-diamine (450 mg, 1.23 mmol) and Et 3 N (249 mg, 2.46 mmol) in THF (15 mL) was added acryloyl chloride (110 mg, 1.23 mmol), the mixture was stirred at 0 o C for 1 hour, concentrated and purified by preparative HPLC (MeCN/H 2 O/TFA) to afford the target compound A-17 as solid (490 mg, yield 95.0%). LC-MS (ESI) m/z: 421.3 [M+H] + . 1 H-NMR (400 MHz, DMSO-d 6 ) δ (ppm): 10.00 (s, 1H), 8.34 (d, J = 2.5 Hz, 1H), 7.65 (dd, J = 9.0, 2.5 Hz, 1H), 7.57 (t, J = 7.6 Hz, 1H), 7.53-7.43(m, 1H), 7.29 (dd, J = 15.6, 7.9 Hz, 2H), 6.82 (dd, J = 13.5, 8.5 Hz, 2H), 6.39 (dd, J = 16.9, 10.1 Hz, 1H), 6.21 (dd, J = 17.0,2.0 Hz, 1H), 6.08 (s, 2H), 5.69 (dd, J = 10.1, 2.0 Hz, 1H), 3.48 (s, 1H), 2.0-1.75 (br, 2H), 1.70-1.50 (m, 3H), 1.47-1.32(m,2H), 1.32-1.15 (m,3H). 19 F-NMR (376 MHz, DMSO-d6) δ (ppm): 117.43. Scheme 22. Synthesis of A-18 Step 1: Synthesis of 2-(cyclohexylamino)-5-nitrobenzoic acid (Compound 22.3) [00363] The mixture of 2-fluoro-5-nitrobenzoic acid (1 g, 5.4 mmol) and cyclohexanamine (535 mg, 5.4 mmol) in pyridine (20 mL) was heated at 60 o C Under N 2 for 16 hours. The resulting mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 30% v/v) to afford the target compound 22.3 as solid (1.5 g, yield 99.9%). LC-MS (ESI) m/z: 265 [M+H] + . Step 2: Synthesis of 2-(cyclohexylamino)-5-nitrobenzohydrazide (Compound 22.4) [00364] The mixture of 2-(cyclohexylamino)-5-nitrobenzoic acid (1.4 g, 0.19 mmol) in EtOH (30 mL) and H 2 SO 4 (30 mL) was heated at 100 o C for 16 hours. The resulting mixture was concentrated in vacuum, the residue was adjusted to pH 9 with concentrated ammonia solution and extracted with ether (100 mL x 2), the combined extracts were dried over anhydrous Na 2 SO 4 , filtered and concentrated in vacuum, to the residue was added hydrazine hydrate (98%, 1 mL), the resulting mixture was heated at 120 o C for 3 hours, concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 30% v/v) to obtain the target compound 22.4 as oil (700 mg, yield 36.6%). LC-MS (ESI) m/z: 279[M+H] + . Step 3: Synthesis of N-cyclohexyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-4-nitroanilin e (Compound 22.6) [00365] The mixture of 2-(cyclohexylamino)-5-nitrobenzohydrazide (650 mg, 2.34 mmol) and 1,1,1-triethoxyethane (379 mg, 2.34 mmol) in 1,4-dioxane (30 mL) was heated at 110 o C for 16 hours. The resulting mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 50% v/v) to obtain the target compound 22.6 as solid (600 mg, yield 84.9%). LC-MS (ESI) m/z: 303[M+H] + . Step 4: Synthesis of N1-cyclohexyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)benzene-1,4- diamine (Compound 22.7) [00366] To the solution of N-cyclohexyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-4-nitroanilin e (550 mg, 1.82 mmol) in EtOH (15 mL) and THF (15 mL) was added Raney nickel (88 mg, 0.18 mmol), and then N2H4·H 2 O (110 mg, 1.82 mmol). The resulting mixture was stirred at rt for 1 hour and filtered, the filtrate was concentrated under reduced pressure to leave the crude target compound 22.7 as oil (500 mg, yield 99.9%). LC-MS (ESI) m/z: 273[M+H] + . Step 5: Synthesis of N-(4-(cyclohexylamino)-3-(5-methyl-1,3,4-oxadiazol-2- yl)phenyl)acrylamide (Compound A-18) [00367] To the mixture of N1-cyclohexyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)benzene-1,4- diamine (450 mg, 1.65 mmol) and Et 3 N (100 mg, 3.31 mmol) in THF (20 mL) was added acryloyl chloride (64 mg, 1.65 mmol), the resulting mixture was stirred at 0 o C for 1 hour, concentrated and monitored by preparative HPLC (MeCN/H 2 O/TFA) to obtain the target compound A-18 as solid (314 mg, yield 58.2%). LC-MS (ESI) m/z: 327 [M+H] + . 1 H-NMR (400 MHz, DMSO-d 6 ) δ (ppm): 10.03 (s, 1H), 8.22 (d, J = 2.5 Hz, 1H), 7.57 (dd, J = 9.1, 2.5 Hz, 1H), 7.32 (d, J = 7.7 Hz, 1H), 6.90 (d, J = 9.2 Hz, 1H), 6.39 (dd, J = 16.5, 9.6 Hz, 1H), 6.22 (dd, J = 17.0, 2.1 Hz, 1H), 5.71 (dd, J = 10.0, 2.1 Hz, 1H), 3.55-3.50 (br, 1H), 2.59 (s, 3H), 1.97 (d, J = 9.7 Hz, 2H), 1.75-1.65 (m, 2H), 1.60-1.50 (m, 1H), 1.50-1.35 (m, 2H), 1.35- 1.26 (m, 3H).
Scheme 23. Synthesis of A-19 Step 1: Synthesis of 4-iodo-1-(3-(trifluoromethyl)benzyl)-1H-imidazole (Compound 23.3) [00368] To the solution of 5-iodo-1H-imidazole (1 g, 5.18 mmol) in DMF (20 mL) was added NaH (248 mg, 6.2 mmol) under N 2 , the mixture was stirred at 0 o C for 0.5 hour, and then 1-(bromomethyl)-3-(trifluoromethyl)benzene (1.24 g, 5.18 mmol) was added, the resulting mixture was stirred at rt for 1 hours, concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 30% v/v) to obtain the target compound 23.3 as solid (1.5 g, yield 82.8%). LC-MS (ESI) m/z: 353[M+H] + . Step 2: Synthesis of N-cyclohexyl-4-nitro-2-(1-(3-(trifluoromethyl)benzyl)-1H-imi dazol- 4-yl)aniline (Compound 23.5) [00369] The mixture of 4-iodo-1-(3-(trifluoromethyl)benzyl)-1H-imidazole (300 mg, 0.96 mmol), N-cyclohexyl-4-nitro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborol an-2-yl)aniline (300 mg, 0.96 mmol), Cs 2 CO 3 (828 mg, 2.52 mmol) and Pd(dppf)Cl 2 (62.4 mg, 0.096 mmol) in DMF (2 mL) was heated at 100 o C under N 2 for 16 hours. The resulting mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 30% v/v) to obtain the target compound 23.5 as solid (120 mg, yield 31.7%). LC-MS (ESI) m/z: 445[M+H] + . Step 3: Synthesis of N1-cyclohexyl-2-(1-(3-(trifluoromethyl)benzyl)-1H-imidazol-4 - yl)benzene-1,4-diamine (Compound 23.6) [00370] To the solution of N-cyclohexyl-4-nitro-2-(1-(3-(trifluoromethyl)benzyl)-1H- imidazol-4-yl)aniline (90 mg, 0.18 mmol) in EtOH (10 mL) and THF (10 mL) was added Raney nickel (12 mg, 0.03 mmol), followed by N2H4·H 2 O (9 mg, 0.18 mmol). The mixture was stirred at rt for 1 hour and filtered, the filtrate was concentrated under reduced pressure to leave crude target compound 23.6 as oil (60 mg, yield 71.5%). LC-MS (ESI) m/z: 415[M+H] + . Step 4: Synthesis of N-(4-(cyclohexylamino)-3-(1-(3-(trifluoromethyl)benzyl)-1H- imidazol-4-yl)phenyl)acrylamide (Compound A-19) [00371] To the mixture of N1-cyclohexyl-2-(1-(3-(trifluoromethyl)benzyl)-1H-imidazol-4 - yl)benzene-1,4-diamine (50 mg, 0.12 mmol) and Et 3 N (24 mg, 0.24 mmol) in THF (10 mL) was added acryloyl chloride (18 mg, 0.12 mmol), the mixture was stirred at 0 o C for 1 hour, concentrated and purified by preparative HPLC (MeCN/H 2 O/TFA) to afford the target compound A-19 as solid (5 mg, yield 8.8%). LC-MS (ESI) m/z: 469[M+H] + . 1 H-NMR (400 MHz, CD 3 OD) δ (ppm): 7.89 (s, 1H), 7.70 – 7.54 (m, 5H), 7.40 (s, 1 H), 7.32 (dd, J = 8.8, 2.4 Hz, 1H), 6.76 (d, J = 8.4 Hz, 1H), 6.41 (dd, J = 16.8, 10.0 Hz, 1H), 6.31 (dd, J = 16.8, 2.0 Hz, 1H), 5.73 (dd, J = 9.8, 2.1 Hz, 1H), 5.40 (s, 2H), 2.06-1.96 (m, 2H), 1.80-1.70 (m, 2H), 1.68- 1.58 (m, 1H), 1.50-1.21 (m, 6H). Scheme 24. Synthesis of A-20 Step 1: Synthesis of 5-nitro-2-(4-(trifluoromethyl)phenylamino)benzonitrile (Compound 24.3) [00372] To the solution of 4-(trifluoromethyl) aniline (0.96 mg, 6.0 mmol) in DMF (20 mL) was added NaH (0.29 g, 7.2 mmol), the mixture was stirred at 0 o C under N2 for 0.5 hour, and then 2-fluoro-5-nitrobenzonitrile (1 g, 6.0 mmol) was added. The resulting mixture was stirred at 120 o C for 16 hours, concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 30% v/v) to afford the target compound 24.3 as solid (500 mg, yield 27.1%). LC-MS (ESI) m/z: 308 [M+H] + . Step 2: Synthesis of 4-nitro-2-(2H-tetrazol-5-yl)-N-(4-(trifluoromethyl)phenyl)an iline (Compound 24.4) [00373] The mixture of 5-nitro-2-(4-(trifluoromethyl)phenylamino)benzonitrile (400 mg, 1.30 mmol) and NaN 3 (127 mg, 1.95 mmol) in DMF (20 mL) was heated at 120 o C for 16 hours. The resulting mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 30% v/v) to obtain the target compound 24.4 as solid (300 mg, yield 65.7%). LC-MS (ESI) m/z: 351 [M+H] + . Step 3: Synthesis of 2-(2-(2-fluorobenzyl)-2H-tetrazol-5-yl)-4-nitro-N-(4- (trifluoromethyl)phenyl)aniline (Compound 24.6) [00374] The mixture of 4-nitro-2-(2H-tetrazol-5-yl)-N-(4-(trifluoromethyl)phenyl)an iline (250 mg, 0.71 mmol), 1-(bromomethyl)-2-fluorobenzene (134 mg, 0.71 mmol) and K2CO 3 (196 mg, 1.42 mmol) in DMF (15 mL) was stirred at rt for 3 hours. The resulting mixture was concentrated and purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 40% v/v) to obtain the target compound 24.6 as solid (300 mg, yield 91.7%). LC-MS (ESI) m/z: 459 [M+H] + . Step 4: Synthesis of 2-(2-(2-fluorobenzyl)-2H-tetrazol-5-yl)-N1-(4- (trifluoromethyl)phenyl)benzene-1,4-diamine (Compound 24.7) [00375] To the solution of 2-(2-(2-fluorobenzyl)-2H-tetrazol-5-yl)-4-nitro-N-(4- (trifluoromethyl)phenyl)aniline (250 mg, 0.55 mmol) in EtOH (10 mL) and THF (10 mL) was added Raney nickel (20 mg, 0.05 mmol), and then N2H4·H 2 O (27 mg, 0.55 mmol) was added. The mixture was stirred at rt for 1 hour and filtered, the filtrate was concentrated under reduced pressure to leave the crude compound 24.7 as oil (200 mg, yield 71.4%). LC- MS (ESI) m/z: 429 [M+H] + . Step 5: Synthesis of N-(3-(2-(2-fluorobenzyl)-2H-tetrazol-5-yl)-4-(4-(trifluorome thyl) phenylamino)phenyl)acrylamide (Compound A-20) [00376] To the mixture of 2-(2-(2-fluorobenzyl)-2H-tetrazol-5-yl)-N1-(4-(trifluorometh yl) phenyl)benzene-1,4-diamine (200 mg, 0.47 mmol) and Et3N (97 mg, 0.94 mmol) in THF (15 mL) was added acryloyl chloride (42 mg, 0.47 mmol), the mixture was stirred at 0 o C for 1 hour, concentrated and purified by preparative HPLC (MeCN/H 2 O/TFA) to obtain the target compound A-20 as solid (171 mg, yield 76.0%). LC-MS (ESI) m/z: 483 [M+H] + . 1 H-NMR (400 MHz, DMSO-d6) δ (ppm) 10.32 (s, 1H), 8.59 (s, 1H), 8.37 (d, J = 2.4 Hz, 1H), 7.83 (dd, J = 9.1, 2.3 Hz, 1H), 7.49 (dd, J = 8.1, 3.8 Hz, 5H), 7.34 – 7.18 (m, 2H), 7.03 (d, J = 8.7 Hz, 2H), 6.43 (dd, J = 17.0, 10.1 Hz, 1H), 6.27 (dd, J = 17.0, 2.0 Hz, 1H), 6.04 (s, 2H), 5.77 (dd, J = 10.1, 2.0 Hz, 1H). 19 F-NMR (376 MHz, DMSO-d6) δ (ppm): -59.52, -117.53. Scheme 25. Synthesis of A-21 Step 1: Synthesis of 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxabo rolane (Compound 25.3) [00377] To the mixture of 2-bromo-1-fluoro-4-nitrobenzene (500 mg, 2.3 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (640 mg, 2.5 mmol) and KOAc (450 mg, 4.6 mmol) in 1,4-dioxane (25 mL) and DMSO (0.5 mL) was added Pd(dppf)Cl 2 (84 mg, 0.11 mmol), the mixture was heated at 90 o C under N 2 for 14 hours. The mixture was cooled down to rt, diluted with water (100 mL) and extracted with EtOAc (3 x 100 mL), the combined organics were washed with brine (200 mL), dried over anhydrous Na2SO 4 , filtered and concentrated to leave the crude compound 25.3 as oil (400 mg, yield 65.6%). LC-MS (ESI) m/z: 186.1 [M-82] + . Step 2: Synthesis of 2-(2-fluoro-5-nitrophenyl)pyrimidine (Compound 25.5) [00378] To the mixture of 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane (400 mg, 1.50 mmol), 2-bromopyrimidine (237 mg, 1.50 mmol) and K 3 PO 4 (954 mg, 4.50 mmol) in iPrOH (5 mL), toluene (5 mL) and H 2 O (5 mL) was added Pd(dppf)Cl2 (54 mg, 0.075 mmol), the mixture was heated at 85 o C under N2 for 4 hours and concentrated in vacuum, the residue was purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 30% in v/v) to obtain the target compound 25.5 as solid (300 mg, yield 91.4%). LC-MS (ESI) m/z: 220.1 [M+H] + . Step 3: Synthesis of 4-nitro-2-(pyrimidin-2-yl)-N-(4-(trifluoromethyl)phenyl)anil ine (Compound 25.7) [00379] To the mixture of 2-(2-fluoro-5-nitrophenyl)pyrimidine (250 mg, 1.14 mmol) in DMF (10 mL) was added NaH (54 mg, 2.25 mmol), the mixture was stirred at 0 o C under N 2 for 0.5 hour, and then 4-(trifluoromethyl)aniline (183 mg, 1.14 mmol) was added, the mixture was stirred at 120 o C for 16 hours and concentrated in vacuum, the residue was purified by flash column chromatography on silica gel (ethyl acetate in petroleum ether = 30% in v/v) to obtain the target compound 25.7 as solid (200 mg, yield 48.7%). LC-MS (ESI) m/z: 361.0 [M+H] + . Step 4: Synthesis of 2-(pyrimidin-2-yl)-N1-(4-(trifluoromethyl)phenyl)benzene-1,4 - diamine (Compound 25.8) [00380] To the mixture of 4-nitro-2-(pyrimidin-2-yl)-N-(4-(trifluoromethyl)phenyl)anil ine (150 mg, 0.42 mmol) and Raney nickel (16 mg, 0.04 mmol) in EtOH (10 mL) and THF (10 mL) was added N 2 H 4 ·H 2 O (80 mg, 1.682 mmol), the mixture was stirred at rt for 1 hour and filtered through celite, the filtrate was concentrated under reduced pressure to leave the crude compound 25.8 as oil (100 mg, yield 72.9%). LC-MS (ESI) m/z: 331.1 [M+H] + . Step 5: Synthesis of N-(3-(pyrimidin-2-yl)-4-(4-(trifluoromethyl)phenylamino)phen yl) acrylamide (Compound A-21) [00381] To the mixture of 2-(pyrimidin-2-yl)-N1-(4-(trifluoromethyl)phenyl) benzene-1,4- diamine (100 mg, 0.31 mmol) and Et3N (62 mg, 0.62 mmol) in THF (10 mL) was added acryloyl chloride (28 mg, 0.31 mmol), the mixture was stirred at 0 o C for 1 hour. The resulting mixture was concentrated and purified by preparative HPLC (MeCN/H 2 O/THF) to obtain the target compound A-21 as solid (45 mg, yield 38.7%). LC-MS (ESI) m/z: 385.2 [M+H] + . 1 H- NMR (400 MHz, DMSO-d6) δ (ppm) 10.71 (s, 1H), 10.28 (s, 1H), 8.99 (d, J = 4.7 Hz, 2H), 8.71 (s, 1H), 7.86 (d, J = 8.3 Hz, 1H), 7.61 – 7.44 (m, 4H), 7.31 (d, J = 8.1 Hz, 2H), 6.46 (dd, J = 16.8, 9.9 Hz, 1H), 6.27 (d, J = 16.6 Hz, 1H), 5.76 (d, J = 9.5 Hz, 1H). 19 F-NMR (376 MHz, DMSO-d 6 ) δ (ppm): -59.74. Scheme 26. Synthesis of A-22 Step 1: Synthesis of N-(3-(pyrimidin-2-yl)-4-(4-(trifluoromethyl)phenylamino) phenyl)propionamide (Compound A-22) [00382] To the solution of 2-(pyrimidin-2-yl)-N1-(4-(trifluoromethyl)phenyl)benzene-1,4 - diamine (180 mg, 0.55 mmol) in THF (20 mL) was added Et3N (111 mg, 1.1 mmol) and propionyl chloride (50 mg, 0.55 mmol), the mixture was stirred at 0 o C for 1 hour, concentrated and purified by prep-HPLC (MeCN/H 2 O/TFA) to obtain the target compound A-22 as solid (21 mg, yield 10.0%). LC-MS (ESI) m/z: 386[M+H]+. 1 H NMR (400 MHz, DMSO-d6) δ (ppm): 10.60 (s, 1H), 9.95 (s, 1H), 8.98 (d, J = 4.9 Hz, 2H), 8.62 (d, J = 2.5 Hz, 1H), 7.75 (dd, J = 8.9, 2.5 Hz, 1H), 7.55 (d, J = 8.6 Hz, 2H), 7.52 – 7.46 (m, 2H), 7.28 (d, J = 8.5 Hz, 2H), 2.33 (q, J = 7.5 Hz, 2H), 1.11 (t, J = 7.6 Hz, 3H). E QUIVALENTS AND SCOPE [00383] In the claims articles such as “a,” “an,” and “the” may mean one or more than one unless indicated to the contrary or otherwise evident from the context. Claims or descriptions that include “or” between one or more members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context. The disclosure includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The disclosure includes embodiments in which more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process. [00384] Furthermore, the disclosure encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, and descriptive terms from one or more of the listed claims is introduced into another claim. For example, any claim that is dependent on another claim can be modified to include one or more limitations found in any other claim that is dependent on the same base claim. Where elements are presented as lists, e.g., in Markush group format, each subgroup of the elements is also disclosed, and any element(s) can be removed from the group. It should it be understood that, in general, where the disclosure, or aspects described herein, is/are referred to as comprising particular elements and/or features, certain embodiments described herein or aspects described herein consist, or consist essentially of, such elements and/or features. For purposes of simplicity, those embodiments have not been specifically set forth in haec verba herein. It is also noted that the terms “comprising” and “containing” are intended to be open and permits the inclusion of additional elements or steps. Where ranges are given, endpoints are included. Furthermore, unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or sub–range within the stated ranges in different embodiments described herein, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise. [00385] This application refers to various issued patents, published patent applications, journal articles, and other publications, all of which are incorporated herein by reference. If there is a conflict between any of the incorporated references and the instant specification, the specification shall control. In addition, any particular embodiment of the present disclosure that falls within the prior art may be explicitly excluded from any one or more of the claims. Because such embodiments are deemed to be known to one of ordinary skill in the art, they may be excluded even if the exclusion is not set forth explicitly herein. Any particular embodiment described herein can be excluded from any claim, for any reason, whether or not related to the existence of prior art. [00386] Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation many equivalents to the specific embodiments described herein. The scope of the present embodiments described herein is not intended to be limited to the above Description, but rather is as set forth in the appended claims. Those of ordinary skill in the art will appreciate that various changes and modifications to this description may be made without departing from the spirit or scope of the present disclosure, as defined in the following claims.