EGFR inhibitors in cancer treatment

Abstract

The present invention is directed to the compounds of Formula (A) inhibitors of EGFR. The inhibitors described herein can be useful in the treatment of diseases or disorders associated with EGFR, such as is lung cancer. In particular, the invention is concerned with compounds and pharmaceutical compositions inhibiting EGFR kinase activity in a cell, methods of treating diseases or disorders associated with EGFR, and methods of synthesizing these compounds.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and benefit of U.S. Provisional Patent Application Serial No. 63 / 332835 filed April 20, 2022, entitled “EGFR Inhibitors in Cancer Treatment”, the disclosure of which is incorporated by reference in its entirety for all purposes. FIELD OF INVENTION

[0002] The present invention is directed to inhibitors of Epidermal Growth Factor Receptor (EGFR or EGF-receptor) - receptor of tyrosine kinase family. The inhibitors described herein can be useful in the treatment of diseases or disorders associated with EGFR, such as cancer. In particular, the invention is concerned with compounds and pharmaceutical compositions inhibiting EGFR, methods of treating diseases or disorders associated with EGFR, and methods of synthesizing these compounds. BACKGROUND

[0003] The phy siological function of the epidermal growth factor receptor (EGFR) is to regulate epithelial tissue development and homeostasis. The epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor for various growth factors including EGF (epidermal growth factor), TGF-a (transforming growth factor-a) and other EGF-like ligands. The EGFR pathway plays an important role in pulmonary physiology especially the function of epithelial cells via signaling transduction that regulates key cellular processes such as self-renew, w'ound-healing, proliferation, survival, adhesion, migration, and differentiation. Epidermal growth factor receptor (EGFR) is a transmembrane protein with cytoplasmic kinase activity that transduces important growth factor signaling from the extracellular milieu to the cell.

[0004] EGFR gene amplification, overexpression, and mutation are frequently observed in various cancer indications and are associated with a poor prognosis. The epidermal growth factor receptor (EGFR) over-activation is observed in a vast number of cancers.

[0005] In pathological settings, mostly in lung and breast cancer and in glioblastoma, the EGFR is a driver of tumorigenesis. Inappropriate activation of the EGFR in cancer mainly results from amplification and point mutations at the genomic locus, but transcriptional upregulation or ligand overproduction due to autocrme / paracnne mechanisms has also been described. Moreover, the EGFR is increasingly recognized as a biomarker of resistance in tumors, as its amplification or secondary mutations have been found to arise under drug pressure. This evidence, in addition to the prominent function that this receptor plays in normal epithelia, has prompted intense investigations into the role of the EGFR both at physiological and at pathological level.

[0006] High abundance of EGFR and large internal deletions are frequently observed in brain tumors, whereas point mutations and small insertions within the kinase domain are common in lung cancer.

[0007] Given that more than 60% of non-small cell lung carcinomas (NSCLCs) express EGFR, EGFR has become an important therapeutic target for the treatment of these tumors. EGFR inhibitors have been widely used in treatment of non-small cell lung cancer (NSCLC).

[0008] Several reports have been published recently demonstrating a beneficial effect of epidermal growth factor receptor (EGFR) inhibitors in improving pathological and behavioral conditions in neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD) and Amyotrophic Lateral Sclerosis (ALS) as well as the brain and spinal cord injuries (SCI).

[0009] In summary, EGFR is a promising drug target for cancer therapy. Targeting EGFR and its downstream signaling cascades are regarded as a rational and valuable approach in cancer therapy. Several synthetic EGFR tyrosine kinase inhibitors (TKIs) have been evaluated in recent years, mostly exhibited clinical efficacy in relevant models and categorized into first, second, third and fourth generation. However, studies are still ongoing to find more efficient EGFR inhibitors in light of the resistance to the current inhibitors.

[0010] EGFR inhibitors have produced impressive therapeutic benefits to responsive types of cancers. Unfortunately, however, patients who initially respond to anti-EGFR drugs almost inevitably develop resistance. Resolving mechanisms of drug resistance translates to higher granularity maps of signaling pathways and it holds the promise of prolonging patient response. A novel targeted therapy that is able to specifically address the EGFR-C797S acquired resistance mutation would be highly beneficial for those patients.

[0011] In particular, patients with primary resistance to approved anti-EGFR therapies, due to EGFR exon20 insertions, have only few treatment options to date and there is a great need for novel alternative and / or improved therapeutics to provide these patients with an efficacious, well tolerable therapy. Therefore, potent inhibitors of mutant EGFR, particularly of mutant EGFR with exon20 insertion mutations that show improved selectivity versus wild-type EGFR, represent valuable compounds that should complement therapeutic options either as single agents or in combination with other drugs. SUMMARY

[0012] A first aspect of the invention relates to compounds of Formula (A): L1----Y----L2 (A), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein Ra is selected from H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, =0, NR3R4, CN, NO2, COOR1, CONR3R4; Rb, Rc, Rd are each independently selected from H, halogen, OH, NH2, CN, NO2, Ci-Cs alkyl, and Ci-Ce alkoxy, wherein alkyl or alkoxy is optionally substituted with one or more halogen, CN; X is selected from a bond, O, NR1, C(R2)2, S, S(0), S(0)2, C(0), C(0)0, C(O)NR1, 0C(0)0, N(R2)C(O)NR2, arenediyl; R1 is selected from H, Ci-Ce alkyl, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Ci-Ce acyl, heterocycle, aryl. heteroaryl, and S(O)2R2 wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, Ci-Ce alkyl, Ci-Ce alkoxy, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, heteroaryl; each R2 is independently selected from H, Ci-Cs alkyl, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, and heteroaryl wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, Ci-Ce alkyl, Ci-Ce alkoxy, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, heteroaryl; Y is selected from a bond, 0, NR1, C(R2)2, S, S(0), S(0)2, C(0), C(0)0, C(0)NR1, 0C(0)0, N(R2)C(O)NR2; Z is selected from a bond, 0, C(R2)2; L1 is selected from heterocyclediyl-Ci-Cio-alkanediyl, C1-C10 alkanediyl, C2-C10 alkenediyl, C2-C10 alkynediyl, C3-Cio-cycloalkanediyl, C3-Cio-cycloalkanediyl-Ci-Cio-alkanediyl, arenediyl, arenediyl-Ci-Cw-alkanediyl, heterocyclediyl, heterocyclediyl-C(O), heteroarenediyl, heteroarenediyl-Ci-Cw alkanediyl, Ci-Ce alkanediyl-O-Ci-Ce alkanediyl, Ci-Ce alkanediyl-NR1- Ci-Ce alkanediyl, Ci-Ce alkanediyl-C(0)NR1-Ci-C6 alkanediyl, wherein alkanediyl, alkendiyl, alkynediyl, arenediyl, heterocyclediyl or heteroarenediyl heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-C6 alkyl-Ci-C6 alkoxy, Ci-C6 alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2Ci-C6 alkyl; L2 is selected from C1-C10 alkanediyl, C2-Cio alkenediyl, C2-Cio alkynediyl, C3-C10-cycloalkanediyl, Cs-Cio-cycloalkanediyl-Ci-Cio-alkanediyl, arenediyl, arenediyl-Ci-Cio-alkanediyl, heterocyclediyl, heterocyclediyl-Ci-Cio-alkanediyl, heterocyclediyl-C(O), heteroarenediyl, heteroarenediyl-Ci-Cio alkanediyl, Ci-Cs alkanediyl-O-Ci-Ce alkanediyl, Ci-Ce alkanediyl-NR'-Ci-Ce alkanediyl, Ci-Ce alkanediyl-ClOlNR^Ci-Ce alkanediyl, wherein alkanediyl, alkendiyl, alkynediyl, arenediyl, heterocyclediyl or heteroarenediyl heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, Ci-Ce alkyd, Ci-Ce alkoxy, Ci-Cs alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR'-Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2Ci-C6 alkyl; R3 and R4 are each independently selected from H, Ci-Ce alkyl, Ci-Ce acyl and C3-C10 cycloalkyl; or R3 and R4 together with the atoms to which they are attached and any intervening atoms, form a 5-14 membered heterocycle, wherein the heterocycle is optionally substituted with one or more substituents independently selected from halogen, OH, =0, CN, NO2, Ci-Ce alkyl, Ci-Cs alkoxy; wherein, aryl is cyclic, aromatic hydrocarbon groups that have 1 to 3 aromatic rings; arenediyl is an organic radical derived from an aromatic divalent radical by removal of two hydrogens; heterocyclyl is saturated or partially unsaturated 3-10 membered monocyclic, 7-12 membered bicyclic (fused, bridged, or spiro rings), or 11-14 membered tricyclic ring system (fused, bridged, or spiro rings) having one or more heteroatoms selected from O, N, S, P, Se, or B; heterocyclediyl is a divalent functional group derived from heterocycle by the removal of two hydrogen atoms from ring atoms; heteroaryl is a monovalent monocyclic or a polycyclic aromatic radical of 5 to 24 ring atoms, containing one or more ring heteroatoms selected from N, O, S, P, or B, the remaining ring atoms being C; heteroarenediyl is a divalent functional group derived from heteroarenes by the removal of two hydrogen atoms from ring atoms.

[0013] Another aspect of the invention relates to compounds of Formula (I): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof.

[0014] Another aspect of the invention relates to compounds of Formula (II): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof.

[0015] Another aspect of the invention is directed to pharmaceutical compositions comprising a compound of Formula (A), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof and a pharmaceutically acceptable carrier. The pharmaceutical acceptable carrier may further include an excipient, diluent, or surfactant.

[0016] Another aspect of the invention is directed to pharmaceutical compositions comprising a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof and a pharmaceutically acceptable carrier. The pharmaceutical acceptable carrier may further include an excipient, diluent, or surfactant.

[0017] Another aspect of the invention is directed to pharmaceutical compositions comprising a compound of Formula (II), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof and a pharmaceutically acceptable carrier. The pharmaceutical acceptable carrier may further include an excipient, diluent, or surfactant.

[0018] Another aspect of the invention relates to a method of treating a disease or disorder associated with EGFR The method comprises administering to a patient in need of a treatment for diseases or disorders associated with EGFR an effective amount of a compound of Formula (A), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0019] Another aspect of the invention relates to a method of treating a disease or disorder associated with EGFR. The method comprises administering to a patient in need of a treatment for diseases or disorders associated with EGFR an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0020] Another aspect of the invention relates to a method of treating a disease or disorder associated with EGFR. The method comprises administering to a patient in need of a treatment for diseases or disorders associated with EGFR an effective amount of a compound of Formula (II), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0021] Another aspect of the invention is directed to a method of inhibiting of EGFR. The method involves administering to a patient in need thereof an effective amount of a compound of Formula (A), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0022] Another aspect of the invention is directed to a method of inhibiting of EGFR. The method involves administering to a patient in need thereof an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0023] Another aspect of the invention is directed to a method of inhibiting of EGFR. The method involves administering to a patient in need thereof an effective amount of a compound of Formula (II), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0024] Another aspect of the present invention relates to compounds of Formula (A), or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, tautomers, or pharmaceutical compositions thereof, for use in the manufacture of a medicament for inhibiting EGFR.

[0025] Another aspect of the present invention relates to compounds of Formula (I), or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, tautomers, or pharmaceutical compositions thereof, for use in the manufacture of a medicament for inhibiting EGFR.

[0026] Another aspect of the present invention relates to compounds of Formula (II), or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, tautomers, or pharmaceutical compositions thereof, for use in the manufacture of a medicament for inhibiting EGFR.

[0027] Another aspect of the present invention relates to the use of compounds of Formula (A), or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, tautomers, or pharmaceutical compositions thereof, in the treatment of diseases and disorders associated with EGFR.

[0028] Another aspect of the present invention relates to the use of compounds of Formula (I), or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, tautomers, or pharmaceutical compositions thereof, in the treatment of diseases and disorders associated with EGFR.

[0029] Another aspect of the present invention relates to the use of compounds of Formula (II), or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, tautomers, or pharmaceutical compositions thereof, in the treatment of diseases and disorders associated with EGFR.

[0030] Another aspect of the present invention relates to compounds of Formula (A), or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, tautomers, or pharmaceutical compositions thereof, for use in the manufacture of a medicament for treating or preventing a disease or disorder disclosed herein.

[0031] Another aspect of the present invention relates to compounds of Formula (I), or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, tautomers, or pharmaceutical compositions thereof, for use in the manufacture of a medicament for treating or preventing a disease or disorder disclosed herein.

[0032] Another aspect of the present invention relates to compounds of Formula (II), or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, tautomers, or pharmaceutical compositions thereof, for use in the manufacture of a medicament for treating or preventing a disease or disorder disclosed herein.

[0033] Another aspect of the invention is directed to a method of treating or preventing a disease or disorder disclosed herein in a subject in need thereof. The method involves administering to a patient in need of the treatment an effective amount of a compound of Formula (A), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0034] Another aspect of the invention is directed to a method of treating or preventing a disease or disorder disclosed herein in a subject in need thereof. The method involves administering to a patient in need of the treatment an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0035] Another aspect of the invention is directed to a method of treating or preventing a disease or disorder disclosed herein in a subject in need thereof. The method involves administering to a patient in need of the treatment an effective amount of a compound of Formula (II), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0036] Another aspect of the present invention relates to the use of compounds of Formula (A), or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, tautomers, or pharmaceutical compositions thereof, in the treatment of a disease or disorder disclosed herein.

[0037] Another aspect of the present invention relates to the use of compounds of Formula (I), or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, tautomers, or pharmaceutical compositions thereof, in the treatment of a disease or disorder disclosed herein.

[0038] Another aspect of the present invention relates to the use of compounds of Formula (II), or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, tautomers, or pharmaceutical compositions thereof, in the treatment of a disease or disorder disclosed herein.

[0039] The present invention further provides methods of treating a disease or disorder associated with EGFR, comprising administering to a patient suffering from at least one of said diseases or disorders a compound of Formula (A), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0040] The present invention further provides methods of treating a disease or disorder associated with EGFR, comprising administering to a patient suffering from at least one of said diseases or disorders a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0041] The present invention further provides methods of treating a disease or disorder associated with EGFR, comprising administering to a patient suffering from at least one of said diseases or disorders a compound of Formula (II), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0042] The present invention provides inhibitors of EGFR that are therapeutic agents in the treatment of diseases and disorders.

[0043] The present invention further provides compounds and compositions with an improved efficacy and safety profile relative to known inhibitors of EGFR. The present disclosure also provides agents with novel mechanisms of action toward EGFR in the treatment of various types of diseases.

[0044] The present invention further provides methods of treating a disease or disorder associated with EGFR, comprising administering to a patient suffering from at least one of said diseases or disorders a compound of Formula (A), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0045] The present invention further provides methods of treating a disease or disorder associated with EGFR, comprising administering to a patient suffering from at least one of said diseases or disorders a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0046] The present invention further provides methods of treating a disease or disorder associated with EGFR, comprising administering to a patient suffering from at least one of said diseases or disorders a compound of Formula (II), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0047] The present invention provides inhibitors of EGFR that are therapeutic agents in the treatment of diseases and disorders.

[0048] The present invention further provides methods of treating a disease, disorder, or condition selected from Inflammatory Skin and Bowel Disease, Neonatal, 2 (NISBD2); Lung Cancer; Lung Cancer Susceptibility 3 (LNCR3); Lung Squamous Cell Carcinoma; Gliosarcoma; Brain Stem Glioma; Adenocarcinoma; Colorectal Cancer; Glioblastoma; Breast Cancer; Squamous Cell Carcinoma; Small Cell Cancer of the Lung; Lung Squamous Cell Carcinoma; Inflammatory Skin and Bowel Disease, Neonatal, 2; Gastric Cancer; Prostate Cancer; Squamous Cell Carcinoma, Head and Neck; Pancreatic Cancer; Brain Cancer; Ovarian Cancer; Esophageal Cancer; Giant Cell Glioblastoma; Gliosarcoma; Lung Benign Neoplasm; Glioma; Exanthem; Endometrial Cancer; Adenoid Cystic Carcinoma; Bladder Cancer; Cowden Syndrome 1; Bronchiolo-Alveolar Adenocarcinoma; Oligodendroglioma; Hepatocellular Carcinoma; Lung Non-Squamous NonSmall Cell Carcinoma; High Grade Glioma; Glial Tumor; Laryngeal Squamous Cell Carcinoma; Renal Cell Carcinoma, Nonpapillary; Chronic Kidney Disease; Nasopharyngeal Carcinoma; Oral Squamous Cell Carcinoma; Lung Disease; Interstitial Lung Disease; Adenosquamous Lung Carcinoma; Bile Duct Cancer; Meningioma, Familial; Small Cell Carcinoma; Tumor Predisposition Syndrome; Pancreatic Adenocarcinoma; Diarrhea; Breast Ductal Carcinoma.

[0049] In some aspects, the present disclosure provides a compound obtainable by, or obtained by, a method for preparing compounds described herein (e.g., a method comprising one or more steps described in General Procedure).

[0050] In some aspects, the present disclosure provides an intermediate as described herein, being suitable for use in a method for preparing a compound as described herein (e.g., the intermediate is selected from the intermediates described in Preparative part - P1-P79).

[0051] In some aspects, the present disclosure provides a method of preparing compounds of the present disclosure.

[0052] In some aspects, the present disclosure provides a method of preparing compounds of the present disclosure, comprising one or more steps described herein.

[0053] In some specific non-limiting aspects, the present disclosure provides methods of preparing compounds of the present disclosure, described in the examples 1-20.

[0054] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In the specification, the singular forms also include the plural unless the context clearly dictates otherwise. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below. All publications, patent applications, patents and other references mentioned herein are incorporated by reference. The references cited herein are not admitted to be prior art to the claimed invention. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be limiting. In the case of conflict between the chemical structures and names of the compounds disclosed herein, the chemical structures will control.

[0055] Other features and advantages of the disclosure will be apparent from the following detailed description and claims DETAILED DESCRIPTION

[0056] The present disclosure provides methods of treating, preventing, or ameliorating a disease or disorder in which associated with the inhibition EGFR by administering to a subject in need thereof a therapeutically effective amount of a compound as disclosed herein.

[0057] The details of the disclosure are set forth in the accompanying description below. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, illustrative methods and materials are now described. Other features, objects, and advantages of the disclosure will be apparent from the description and from the claims. In the specification and the appended claims, the singular forms also include the plural unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. All patents and publications cited in this specification are incorporated herein by reference in their entireties. Definitions

[0058] The articles "a" and "an" are used in this disclosure to refer to one or more than one (i.e., to at least one) of the grammatical object of the article. By way of example, "an element" means one element or more than one element.

[0059] The term "and / or" is used in this disclosure to mean either "and" or "or" unless indicated otherwise.

[0060] The term “optionally substituted” is understood to mean that a given chemical moiety (e.g., an alkyl group) can (but is not required to) be bonded other substituents (e.g., heteroatoms). For instance, an alkyl group that is optionally substituted can be a fully saturated alkyl chain (i.e., a pure hydrocarbon). Alternatively, the same optionally substituted alkyl group can have one or more substituents different from hydrogen. For instance, it can, at any point along the chain be bounded to a halogen atom, a hydroxyl group, or any other substituent described herein. Thus, the term “optionally substituted” means that a given chemical moiety has the potential to contain other functional groups but does not necessarily have any further functional groups. Suitable substituents used in the optional substitution of the described groups include, without limitation, halogen, oxo, -OH,-CN, -COOH, -CH2CN, -O-(Ci-C6) alkyl, (Ci-C6) alkyl, (Ci-C6)alkoxy, (Ci-C6) haloalky 1, (Ci-Ce) haloalkoxy, -O-(C2-Ce) alkenyl, -O-(C2-Ce) alkynyl, (C2-C6) alkenyl, (C2-C6) alkynyl, -OH, -OP(O)(OH)2, -OC(O)(Ci-C6) alkyl, -C(O)(Ci-C6) alkyl, -OC(O)O(Ci-C6) alkyl, -NH2, -NH((Ci-C6) alkyl), -N((Ci-C6) alkyl)2, -NHC(O)(Ci-C6) alkyl, -C(O)NH(Ci-C6) alkyl, -S(O)2(Ci-C6) alkyl, -S(O)NH(Ci-C6)alkyl, and -S(O)N((Ci-C6)alkyl)2. The substituents can themselves be optionally substituted. “Optionally substituted” as used herein also refers to substituted or unsubstituted whose meaning is described below.

[0061] As used herein, the term “substituted” means that the specified group or moiety bears one or more suitable substituents wherein the substituents may connect to the specified group or moiety at one or more positions. For example, an aryl substituted with a cycloalkyl may indicate that the cycloalkyl connects to one atom of the aryl with a bond or by fusing with the aryl and sharing two or more common atoms.

[0062] As used herein, the term “unsubstituted” means that the specified group bears no substituents.

[0063] Unless otherwise specifically defined, the term "aryl" refers to cyclic, aromatic hydrocarbon groups that have 1 to 3 aromatic rings, including monocyclic or bicyclic groups such as phenyl, biphenyl or naphthyl. Where containing two aromatic rings (bicyclic, etc.), the aromatic rings of the aryl group may be joined at a single point (e.g, biphenyl), or fused (e.g, naphthyl). The aryl group may be optionally substituted by one or more substituents, e.g., 1 to 5 substituents, at any point of attachment. Exemplary substituents include, but are not limited to, -H, -halogen, -O-(Ci-C6)alkyl, (Ci-C6)alkyl, -O-(C2-C6)alkenyl, -O-(C2-C6) alkynyl, (C2-C6)alkenyl, (C2- C6)alkynyl, -OH, -OP(O)(OH)2, -OC(O)(Ci-C6)alkyl, -C(O)(Ci-C6) alkyl, -OC(O)O(Ci-C6)alkyl, -NH2, -NH((Ci-C6)alkyl), -N((Ci-C6)alkyl)2, -S(O)2-(Ci-C6) alkyl, -S(O)NH(Ci-Ce)alkyl, and -S(O)N((Ci-Ce)alkyl)2. The substituents can themselves be optionally substituted. Furthermore, when containing two fused rings the aryl groups herein defined may have one or more saturated or partially unsaturated ring fused with a fully unsaturated aromatic ring. Exemplary ring systems of these aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl, anthracenyl, phenalenyl, phenanthrenyl, indanyl, indenyl, tetrahydronaphthalenyl, tetrahydrobenzoannulenyl, and the like.

[0064] “Arenediyl”, “arylene" or "arylenyl" means an organic radical derived from an aromatic divalent radical by removal of at least two hydrogens, from a group such as phenyl, naphthyl, indenyl, indanyl and fluorenyl. An arylene is generally present as a bridging or linking group between two other groups. Non-exclusive examples of such arylene groups include 1,2-disubstituted phenyl, 1,3-disubstituted phenyl, 1,4-disubstituted phenyl, etc.

[0065] Unless otherwise specifically defined, "heteroaiyl" means a monovalent monocyclic or a polycyclic aromatic radical of 5 to 24 ring atoms, containing one or more ring heteroatoms selected from N, O, S, P, or B, the remaining ring atoms being C. A polycyclic aromatic radical includes two or more fused rings and may further include two or more spiro-fused rings, e.g., bicyclic, tricyclic, tetracyclic, and the like. Unless otherwise specifically defined, “fused” means two rings sharing two nng atoms. Unless otherwise specifically defined, “spiro-fused” means two nngs sharing one ring atom. Heteroaryl as herein defined also means a bicyclic heteroaromatic group wherein the heteroatom is selected from N, O, S, P, or B. Heteroaryl as herein defined also means a tricyclic heteroaromatic group containing one or more ring heteroatoms selected from N, O, S, P, or B. Heteroaryl as herein defined also means a tetracyclic heteroaromatic group containing one or more ring heteroatoms selected from N, O, S, P, or B. The aromatic radical is optionally substituted independently with one or more substituents described herein. Examples include, but are not limited to, furyl, thienyl, pyrrolyl, pyridyl, pyrazolyl, pyrimidinyl, imidazolyl, isoxazolyl, oxazolyl, oxadiazolyl, pyrazinyl, indolyl, thiophen-2-yl, quinolyl, benzopyranyl, isothiazolyl, thiazolyl, thiadiazole, indazole, benzimidazolyl, thieno[3,2-b]thiophene, triazolyl, triazinyl, imidazo[l,2-b]pyrazolyl, furo[2,3-c]pyridinyl, imidazo[l,2-a]pyridinyl, indazolyl, pyrrolo[2,3-c]pyridinyl, pyrrolo[3,2-c]pyridinyl, pyrazolo[3,4-c]pyridinyl, thieno[3,2-c]pyridinyl, thieno[2,3-c]pyridinyl, thieno[2,3-b]pyridinyl, benzothiazolyl, indolyl, indolinyl, indolinonyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, benzofuran, chromanyl, thiochromanyl, tetrahydroquinolinyl, dihydrobenzothiazine, quinolinyl, isoquinolinyl, 1,6-naphthyridinyl, benzo[de]isoquinolinyl, pyrido[4,3-b][l,6]naphthyridinyl, thieno[2,3-b]pyrazinyl, quinazolinyl, tetrazolo[l,5-a]pyridinyl, [l,2,4]triazolo[4,3-a]pyridinyl, isoindolyl, pyrrolo[2,3-b]pyridinyl, pyrrolo[3,4-b]pyridinyl, pyrrolo[3,2-b]pyridinyl, imidazo[5,4-b]pyridinyl, pyrrolo[l,2-a]pyrimidinyl, tetrahydro pyrrolo[l ,2-a]pyrimidinyl, 3,4-dihydro-2H-l-pyrrolo[2,l-b]pyrimidine, dibenzo[b,d] thiophene, pyridin-2-one, furo[3,2-c]pyridinyl, furo[2,3-c]pyridinyl, lH-pyrido[3,4-b][l,4] thiazinyl, benzooxazolyl, benzoisoxazolyl, furo[2,3-b]pyridinyl, benzothiophenyl, 1,5-naphthyridinyl, furo[3,2-b]pyridine, [l,2,4]triazolo[l,5-a]pyridinyl, benzo[l,2,3]triazolyl, imidazo[l,2-a]pyrimidinyl, [l,2,4]triazolo[4,3-b]pyridazinyl, benzo[c][l,2,5]thiadiazolyl, benzo[c] [1,2,5] oxadiazole, 1,3-dihydro-2H-benzo[d]imidazol-2-one, 3,4-dihydro-2H-pyrazolo [ 1,5 -b] [ 1,2] oxazinyl, 4,5,6,7-tetrahydropyrazolo[l,5-a]pyridinyl, thiazolo[5,4-d]thiazolyl, imidazo[2,l-b][l,3,4]thiadiazolyl, thieno[2,3-b]pyrrolyl, 3H-indolyl, and derivatives thereof. Furthermore, when containing two or more fused rings, the heteroaryl groups defined herein may have one or more saturated or partially unsaturated ring fused with one or more fully unsaturated aromatic ring. In heteroaryl ring systems containing more than two fused rings, a saturated or partially unsaturated ring may further be fused with a saturated or partially unsaturated ring described herein. Furthermore, when containing three or more fused rings, the heteroaryl groups defined herein may have one or more saturated or partially unsaturated ring spiro-fused. Any saturated or partially unsaturated ring described herein is optionally substituted with one or more oxo. Exemplary ring systems of these heteroaryl groups include, for example, indolinyl, indolinonyl, dihydrobenzothiophenyl, dihydrobenzofuran, chromanyl, thiochromanyl, tetrahydroquinolinyl, dihydrobenzothiazme,      3,4-dihydro-lH—isoquinolinyl,      2,3- dihydrobenzofuranyl, benzofuranonyl, indolinyl, oxindolyl, indolyl, l,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-onyl, 7,8-dihydro-6H-pyrido[3,2-b]pyrrolizinyl, 8H-pyrido[3,2-b]pyrrolizinyl, l,5,6,7-tetrahydrocyclopenta[b]pyrazolo[4,3-e]pyridinyl, 7,8-dihydro-6H-pyrido[3,2-b]pyrrolizine, pyrazolo[l,5-a]pyrimidin-7(4H)-only, 3,4-dihydropyrazino[l,2-a]indol l(2H)-onyl, benzofc] [l,2]oxaborol-l(3 / 7)-olyL 6,6a,7,8-tetrahydro-9H-pyrido[2,3-b} puyrrolo[ 1,2-d\ [1,4] oxazin-9-ony 1, or    6a’ ,7 ’ -dihydro-6 ’H,9’H-spiro [cyclopropane-1,8’- pyrido[2,3-6]pyrrolo[l,2-<7][l,4]oxazin]-9’-onyl.

[0066] As used herein, the term “Heteroarendiyl” refers to divalent functional groups derived from heteroarenes by the removal of two hydrogen atoms from ring atoms.

[0067] “Halogen” or “halo” refers to fluorine, chlorine, bromine, or iodine.

[0068] “Alkyl” refers to a straight or branched chain saturated hydrocarbon containing 1-12 carbon atoms. Examples of a (Ci-Cs) alkyl group include, but are not limited to, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl, and isohexyl.

[0069] “Alkanediyl”, “alkylene” or “alkylenyl” refers to a straight or branched chain saturated hydrocarbon biradicals containing 1-12 carbon atoms. Unless specified otherwise, such alkanediyls include substituted alkanediyls. Typical alkylene groups include, but are not limited to, -CH2-, -CH(CH3)-, -C(CH3)2-, -CH2CH2-, -CH2CH(CH3)-, -CH2C(CH3)2-, -ch2ch2ch2-, -CH2CH2CH2CH2-, and the like.

[0070] “Alkoxy” refers to a straight or branched chain saturated hydrocarbon containing 1-12 carbon atoms containing a terminal “O” in the chain, i.e., -O(alkyl). Examples of alkoxy groups include without limitation, methoxy, ethoxy, propoxy, butoxy, / m-butoxy. or pentoxy groups.

[0071] “Alkenyl” refers to a straight or branched chain unsaturated hydrocarbon containing 2-12 carbon atoms. The “alkenyl” group contains at least one double bond in the chain. The double bond of an alkenyl group can be unconjugated or conjugated to another unsaturated group. Examples of alkenyl groups include ethenyl, propenyl, «-butenyl, Ao-butenyl, pentenyl, or hexenyl. An alkenyl group can be unsubstituted or substituted. Alkenyl, as herein defined, may be straight or branched.

[0072] “Alkenediyl” refers to a straight or branched chain alkene biradicals containing 2-12 carbon atoms. Unless specified otherwise, such alkenediyls include substituted alkenediyls. The “alkendiyl” group contains at least one double bond in the chain. The double bond of an alkendiyl group can be unconjugated or conjugated to another unsaturated group. Examples of alkenyl groups include ethendiyl, propendiyl, w-butendiyl, Ao-butendiyl, pentendiyl, or hexendiyl.

[0073] “Alkynyl” refers to a straight or branched chain unsaturated hydrocarbon containing 2-12 carbon atoms. The “alkynyl” group contains at least one triple bond in the chain. Examples of alkenyl groups include ethynyl, propargyl, n-butynyl, Ao-butynyl, pentynyl, or hexynyl. An alkynyl group can be unsubstituted or substituted.

[0074] “Alkynediyl” refers to a straight or branched chain unsaturated hydrocarbon biradicals containing 2-12 carbon atoms. The “alkynediyl” group contains at least one triple bond in the chain. Examples of alkendiyl groups include ethyndiyl, propynediyl, «-butynediyl, Ao-butynediyl, pentynediyl, or hexynediyl. An alkynediyl group can be unsubstituted or substituted.

[0075] “Cycloalkyl” means mono or polycyclic saturated carbon rings containing 3-18 carbon atoms. Polycyclic cycloalkyl may be fused bicyclic cycloalkyl, bridged bicyclic cycloalkyl, or spiro-fused bicyclic cycloalkyl. A polycyclic cycloalkyl comprises at least one non-aromatic ring. Examples of cycloalkyl groups include, without limitations, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptanyl, cyclooctanyl, norbomyl, norborenyl, 1,2,3,4-tetrahydronaphthyl, 2,3-dihydro-lH-indenyl, spiro[3.5]nonyl, spiro [5.5]undecyl, bicyclo[l.l.l]pentanyl, bicyclo[2.2.2]octanyl, or bicyclo[2.2.2]octenyl.

[0076] “Cycloalkanediyl” refers to divalent functional groups derived from cycloalkanes by the removal of two hydrogen atoms from ring atoms. Cycloalkanediyl can be mono or polycyclic saturated carbon ring containing 3-18 carbon atoms. Polycyclic cycloalkanediyl may be fused bicyclic cycloalkyl, bridged bicyclic cycloalkyl, or spiro-fused bicyclic cycloalkanediyl. A polycyclic cycloalkanediyl comprises at least one non-aromatic ring.

[0077] “Heterocyclyl”, “heterocycle” or “heterocycloalkyl” mono or polycyclic rings containing 3-24 atoms which include carbon and one or more heteroatoms selected fromN, O, S, P, or B and wherein the rings are not aromatic. The heterocy cloalkyl ring structure may be substituted by one or more substituents. The substituents can themselves be optionally substituted. Examples of heterocyclyl rings include, but are not limited to, oxetanyl, azetidinyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, oxazolinyl, oxazolidinyl, thiazolinyl, thiazolidinyl, pyranyl, thiopyranyl, tetrahydropyranyl, dioxalinyl, piperidinyl, morpholinyl, thiomorpholinyl, thiomorphohnyl S-oxide, thiomorpholinyl S-dioxide, piperazinyl, azepinyl, oxepinyl, diazepinyl, tropanyl, oxazolidinonyl, and homotropanyl.

[0078] As used herein, the term “Heterocyclediyl” refers to divalent functional groups derived from heterocycle by the removal of two hydrogen atoms from ring atoms.

[0079] The term “aromatic” means a planar ring having 4« + 2 electrons in a conjugated system. As used herein, “conjugated system” means a system of connected p-orbitals with delocalized electrons, and the system may include lone electron pairs.

[0080] The term “haloalkyl” as used herein refers to an alkyl group, as defined herein, which is substituted one or more halogen. Examples of haloalkyl groups include, but are not limited to, tnfluoromethyl, difluoromethyl, pentafluoroethyl, trichloromethyl, etc.

[0081] The term “haloalkoxy” as used herein refers to an alkoxy group, as defined herein, which is substituted with one or more halogen. Examples of haloalkyl groups include, but are not limited to, trifluoromethoxy, difluoromethoxy, pentafluoroethoxy, trichloromethoxy, etc.

[0082] The term “cyano” as used herein means a substituent having a carbon atom joined to a nitrogen atom by a triple bond, i.e., C=N.

[0083] The term "solvate" refers to a complex of variable stoichiometry formed by a solute and solvent. Such solvents for the purpose of the disclosure may not interfere with the biological activity of the solute. Examples of suitable solvents include, but are not limited to, water, MeOH, EtOH, and AcOH. Solvates wherein water is the solvent molecule are ty pically referred to as hydrates. Hydrates include compositions containing stoichiometric amounts of water, as well as compositions containing variable amounts of water.

[0084] The term "isomer" refers to compounds that have the same composition and molecular weight but differ in physical and / or chemical properties. The structural difference may be in constitution (geometric isomers) or in the ability to rotate the plane of polarized light (stereoisomers). With regard to stereoisomers, the compounds of Formula (A) may have one or more asymmetric carbon atom and may occur as racemates, racemic mixtures and as individual enantiomers or diastereomers.

[0085] The term “stereoisomer” refers to compounds that have the same molecular formula and sequence of bonded atoms (constitution) but differ in the three-dimensional orientations of their atoms in space.

[0086] The present disclosure also contemplates isotopically-labelled compounds of Formula I (e.g., those labeled with 2H and 14C). Deuterated (i.e., 2H or D) and carbon-14 (i.e., 14C) isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium may afford certain therapeutic advantages resulting from greater metabolic stability (e.g., increased in vivo half-life or reduced dosage requirements) and hence may be preferred in some circumstances. Isotopically labelled compounds of Formula I can generally be prepared by following procedures analogous to those disclosed in the Schemes and / or in the Examples herein below, by substituting an appropriate isotopically labelled reagent for a non-isotopically labelled reagent.

[0087] The disclosure also includes pharmaceutical compositions comprising a therapeutically effective amount of a disclosed compound and a pharmaceutically acceptable carrier. Representative "pharmaceutically acceptable salts" include, e.g., water-soluble and waterinsoluble salts, such as the acetate, amsonate (4,4-diaminostilbene-2,2-disulfonate), benzenesulfonate, benzoate, bicarbonate, bisulfate, bitartrate, borate, bromide, butyrate, calcium, calcium edetate, camsylate, carbonate, chloride, citrate, clavulariate, dihydrochloride, edetate, edisylate, estolate, esylate, fumarate, gluceptate, gluconate, glutamate, glycollylarsanilate, hexafluorophosphate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isothionate, lactate, lactobionate, laurate, magnesium, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methylsulfate, mucate, napsylate, nitrate, N-methylglucamine ammonium salt, 3-hydroxy-2-naphthoate, oleate, oxalate, palmitate, pamoate, pantothenate, phosphate / diphosphate, picrate, polygalacturonate, propionate, p-toluenesulfonate, salicylate, stearate, subacetate, succinate, sulfate, sulfosalicylate, tannate, tartrate, teoclate, tosylate, triethiodide, and valerate salts.

[0088] A "patient" or “subject” is a mammal, e.g., a human, mouse, rat, guinea pig, dog, cat, horse, cow, pig, or non-human primate, such as a monkey, chimpanzee, baboon, or rhesus.

[0089] An "effective amount" when used in connection with a compound is an amount effective for treating or preventing a disease in a subject as described herein.

[0090] The term "carrier", as used in this disclosure, encompasses carriers, excipients, and diluents and means a material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carry ing or transporting a pharmaceutical agent from one organ, or portion of the body, to another organ, or portion of the body of a subject.

[0091] The term "treating" with regard to a subject, refers to improving at least one symptom of the subject's disorder. Treating includes curing, improving, or at least partially ameliorating the disorder.

[0092] The term "disorder" is used in this disclosure to mean, and is used interchangeably with, the terms disease, condition, or illness, unless otherwise indicated.

[0093] The term "administer", "administering", or "administration" as used in this disclosure refers to either directly administering a disclosed compound or pharmaceutically acceptable salt of the disclosed compound or a composition to a subject, or admmistenng a prodrug derivative or analog of the compound or pharmaceutically acceptable salt of the compound or composition to the subject, which can form an equivalent amount of active compound within the subject's body.

[0094] The term "prodrug," as used in this disclosure, means a compound which is convertible in vivo by metabolic means (e.g., by hydrolysis) to a disclosed compound.

[0095] The term “salt” refers to pharmaceutically acceptable salts.

[0096] The term “pharmaceutically acceptable salt” also refers to a salt of the compositions of the present disclosure having an acidic functional group, such as a carboxylic acid functional group, and a base.

[0097] The symbol «=”, as used in this disclosure, means a double bond in E- or Z-configuration or mixture of E- and Z- configurations.

[0098] “EGFR inhibitor” as used herein refer to compounds of Formula I and / or compositions comprising a compound of Formula I which inhibits EGFR.

[0099] The amount of compound of composition described herein needed for achieving a therapeutic effect may be determined empirically in accordance with conventional procedures for the particular purpose. Generally, for administering therapeutic agents (e.g. compounds or compositions of Formula I (and / or additional agents) described herein) for therapeutic purposes, the therapeutic agents are given at a pharmacologically effective dose. A “pharmacologically effective amount,” “pharmacologically effective dose,” “therapeutically effective amount,” or “effective amount” refers to an amount sufficient to produce the desired physiological effect or amount capable of achieving the desired result, particularly for treating the disorder or disease. An effective amount as used herein would include an amount sufficient to, for example, delay the development of a symptom of the disorder or disease, alter the course of a symptom of the disorder or disease (e.g., slow the progression of a symptom of the disease), reduce or eliminate one or more symptoms or manifestations of the disorder or disease, and reverse a symptom of a disorder or disease. For example, administration of therapeutic agents to a subject suffering from cancer provides a therapeutic benefit not only when the underlying condition is eradicated or ameliorated, but also when the subject reports a decrease in the severity or duration of the symptoms associated with the disease, e.g., a decrease in tumor burden, a decrease in circulating tumor cells, an increase in progression free survival. Therapeutic benefit also includes halting or slowing the progression of the underlying disease or disorder, regardless of whether improvement is realized. Compounds of the Present Disclosure

[0100] In one aspect, the present disclosure provides compounds of Formula (A) and salts, stereoisomers, solvates, prodrugs, isotopic derivatives, and tautomers thereof Wherein Ra, Rb, Rc, Rd, X, L1, Y, L2, and Z are as described herein.

[0101] It is understood that, for a compound of Formula (A), Ra, Rb, Rc, Rd, X, L1, Y, L2, and Z can each be, where applicable, selected from the groups described herein, and any group described herein for any Ra, Rb, Rc, Rd, X, L1, Y, L2, and Z can be combined, where applicable, with any group described herein for one or more of the remainder of Ra, Rb, Rc, Rd, X, L1, Y, L2, and Z.

[0102] In some embodiments, the compound is of Formula (A) or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein Ra is selected from H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, =0, NR3R4, CN, NO2, COOR1, CONR3R4; Rb, Rc, Rd are each independently selected from H, halogen, OH, NH2, CN, NO2, Ci-Ce alkyl, and Ci-Ce alkoxy, wherein alkyl or alkoxy is optionally substituted with one or more halogen, CN; X is selected from a bond, O, NR1, C(R2)2, S, S(O), S(O)2, C(O), C(O)O, C(O)NR3, OC(O)O, N(R2)C(O)NR2, arenediyl; R1 is selected from H, Ci-Ce alkyl, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-Ce alkynyl, Ci-Ce acyl, heterocycle, aryl, heteroaryl, and S(O)2R2 wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, Ci-Ce alkyl, Ci-Ce alkoxy, C3-C10 cycloalkyl, C2-Ce alkenyl, C2-Ce alkynyl, heterocycle, aryl, heteroaryl; each R2 is independently selected from H, Ci-Ce alkyl, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, and heteroaryl wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, Ci-Ce alkyl, Ci-Ce alkoxy, C3-C10 cycloalkyl, C2-Ce alkenyl, C2-C6 alkynyl, heterocycle, aryl, heteroaryl; Y is selected from a bond, 0, NR1, C(R2)2, S, S(0), S(0)2, C(0), C(0)0, C(0)NR3, 0C(0)0, N(R2)C(O)NR2; Z is selected from a bond, 0, C(R2)2; L1 is selected from heterocyclediyl-Ci-Cio-alkanediyl, C1-C10 alkanediyl, C2-Cio alkenediyl, C2-Cw alkynediyl, C3-Cio-cycloalkanediyl, C3-Cio-cycloalkanediyl-Ci-Cio-alkanediyl, arenediyl, arenediyl-Ci-Cw-alkanediyl, heterocyclediyl, heterocyclediyl-C(O), heteroarenediyl, heteroarenediyl-Ci-Cio alkanediyl, Ci-Ce alkanediyl-O-Ci-Ce alkanediyl, Ci-Ce alkanediyl-NR1-Ci-Ce alkanediyl, Ci-Ce alkanediyl-C(0)NR1-Ci-C6 alkanediyl, wherein alkanediyl, alkendiyl, alkynediyl, arenediyl, heterocyclediyl or heteroarenediyl heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Cs alkoxy, Ci-C6 alkyl-Ci-C6 alkoxy, Ci-C6 alkyl-NRkCi-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2Ci-C6 alkyl; L2 is selected from C1-C10 alkanediyl, C2-Cio alkenediyl, C2-Cio alkynediyl, C3-C10-cycloalkanediyl, C3-Cio-cycloalkanediyl-Ci-Cio-alkanediyl, arenediyl, arenediyl-Ci-Cio-alkanediyl, heterocyclediyl, heterocyclediyl-Ci-Cio-alkanediyl, heterocyclediyl-C(O), heteroarenediyl, heteroarenediyl-Ci-Cio alkanediyl, Ci-Ce alkanediyl-O-Ci-Cc alkanediyl, Ci-Ce alkanediyl-NR'-Ci-Ce alkanediyl, Ci-Ce alkanediyl-C(O)NR1-Ci-Ce alkanediyl, wherein alkanediyl, alkendiyl, alkynediyl, arenediyl, heterocyclediyl or heteroarenediyl heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, Ci-C6 alkyd, Ci-C6 alkoxy, Ci-C6 alkyl-Ci-C6 alkoxy, Ci-C6 alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2Ci-C6 alkyl; R3 and R4 are each independently selected from H, Ci-Ce alkyl, Ci-Ce acyl and C3-C10 cycloalkyl; or R3 and R4 together with the atoms to which they are attached and any intervening atoms, form a 5-14 membered heterocycle, wherein the heterocycle is optionally substituted with one or more substituents independently selected from halogen, OH, =0, CN, N02, Ci-Ce alkyl, Ci-Ce alkoxy.

[0103] In some embodiments, the compound is of Formula (A-l): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof.

[0104] In some embodiments, the compound is of Formula (A-l-a): (A-l-a), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof.

[0105] In some embodiments, the compound is of Formula (A-l-b): L1----Y----L2 (A-l-b), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof.

[0106] In some embodiments, the compound is of Formula (A-l-b-H): L1----Y----L2 (A-l-b-H), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof

[0107] In some embodiments, the compound is of Formula (A-A): r5           (A-A), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein Ring A is selected from Cs-Cio-cycloalkane, arene, heterocycle, heteroarene; W is (CH2K; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-C6 alkyl, Ci-C6 alkoxy, Ci-C6 alkyl-Ci-C6 alkoxy, Ci-C6 alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-Ce alkyl, -S(O)2NR3R4, and -S(O)2Ci-Ce alkyl and all other variables are as defined herein.

[0108] In some embodiments, the compound is of Formula (A-A-A): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein i is an integer selected from 0, 1, 2; j is an integer selected from 0, 1, 2; W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10: Q is selected from a bond, CH2, NH, O, S, S(O), S(O)2 and all other variables are as defined herein.

[0109] In some embodiments, the compound is of Formula (A-A-A-I): Ra , or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein i is an integer selected from 0, 1, 2; j is an integer selected from 0, 1, 2; W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; Q is selected from a bond, CH2, NH, O, S, S(O), S(O)2 and all other variables are as defined herein.

[0110] In some embodiments, the compound is of Formula (A-A-A-ll): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein i is an integer selected from 0, 1, 2; j is an integer selected from 0, 1, 2; W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10: Q is selected from a bond, CH2, NH, O, S, S(O), S(O)2 and all other variables are as defined herein.

[0111] In some embodiments, the compound is of Formula (A-A-A-l): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein i is an integer selected from 0, 1, 2; j is an integer selected from 0, 1, 2; W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; Q is selected from a bond, CH2, NH, O, S, S(O), S(O)2 and all other variables are as defined herein.

[0112] In some embodiments, the compound is of Formula (A-A-A-l-I): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein i is an integer selected from 0, 1, 2; j is an integer selected from 0, 1, 2; W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10: Q is selected from a bond, CH2, NH, O, S, S(O), S(O)2 and all other variables are as defined herein.

[0113] In some embodiments, the compound is of Formula (A-A-A-l-II): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein i is an integer selected from 0, 1, 2; j is an integer selected from 0, 1, 2; W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; Q is selected from a bond, CH2, NH, O, S, S(O), S(O)2 and all other variables are as defined herein.

[0114] In some embodiments, the compound is of Formula (A-l-a-I): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein Ring A is selected from Cs-Cio-cycloalkane, arene, heterocycle, heteroarene; W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-C6 alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-Ce alkyl, -S(O)2NR3R4, and -S(O)2Ci-Ce alkyl and all other variables are as defined herein.

[0115] In some embodiments, the compound is of Formula (A-l-a-I-A): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0,1, 2, 3,4, 5, 6, 7, 8, 9, and 10; v is an integer selected from 0, 1, 2, 3, 4 and 5; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Cg alkoxy, Ci-C6 alkyl-Ci-Ce alkoxy, Ci-C6 alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-Ce alkyl; and all other variables are as defined herein.

[0116] In some embodiments, the compound is of Formula (A-l-a-I-A-1): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein v is an integer selected from 0, 1, 2, 3, 4 and 5; R5 is selected from H, halogen, OH, oxo, CN, Ci-C6 alkyl, Ci-C6 alkoxy, Ci-C6 alkyl-Ci-C6 alkoxy, Ci-C6 alkyl-NR^Ci-Cg alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-Ce alkyl, -S(O)2NR3R4, and -S(0)2Ci-Ce alkyl; and all other variables are as defined herein.

[0117] In some embodiments, the compound is of Formula (A-l-a-I-B): R5                      (A-l-a-I-B), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)„; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl and all other variables are as defined herein.

[0118] In some embodiments, the compound is of Formula (A-l -a-I-B-0): R5                      (A-l-a-I-B-0), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-C6 alkyl-NR^Ci-Cs alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl and all other variables are as defined herein.

[0119] In some embodiments, the compound is of Formula (A-l-a-I-B-1): R5                      (A-l-a-I-B-1), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Cs alkoxy, Ci-Ce alkyl-NR^Ci-Cfi alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl and all other variables are as defined herein.

[0120] In some embodiments, the compound is of Formula (A-l-a-I-B-2): (A-l-a-I-B-2), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Cg alkoxy, Ci-Cg alkyl-Ci-Cg alkoxy, Ci-Cg alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-Cg alkyl, -S(O)2NR3R4, and -S(O)2Ci-Cg alkyl and all other variables are as defined herein.

[0121] In some embodiments, the compound is of Formula (A-l-a-I-B-3): I R5               (A-l-a-I-B-3), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Cg alkoxy, Ci-Cg alkyl-Ci-Cg alkoxy, Ci-Cg alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-Cg alkyl, -S(O)2NR3R4, and -S(O)2Ci-Cg alkyl and all other variables are as defined herein.

[0122] In some embodiments, the compound is of Formula (A-l-a-I-C): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein Ring His 3-10 membered monocyclic or bicyclic heterocycle comprising 1-3 heteroatoms selected from N, O, S; W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected fromH, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Cs alkoxy, Ci- C6 alkyl-NRkCi-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci- G, alkyl and all other variables are as defined herein.

[0123] In some embodiments, the compound is of Formula (A-l-a-I-C-1): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0,1, 2, 3,4, 5, 6, 7, 8, 9, and 10; v is an integer selected from 0, 1, 2, 3, 4 and 5; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Cg alkoxy, Ci-C6 alkyl-Ci-C6 alkoxy, Ci-C6 alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-Ce alkyl; and all other variables are as defined herein.

[0124] In some embodiments, the compound is of Formula (A-l-a-I-C-l-a): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Cs alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0125] In some embodiments, the compound is of Formula (A-l-a-I-C-l-a-I): R5                (A-l-a-I-C-l-a-I), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0126] In some embodiments, the compound is of Formula (A-l-a-I-C-l-a-II): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Cg alkoxy, Ci-Cg alkyl-Ci-Cg alkoxy, Ci-Cg alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-Cg alkyl, -S(O)2NR3R4, and -S(O)2Ci-Cg alkyl; and all other variables are as defined herein.

[0127] In some embodiments, the compound is of Formula (A-l-a-I-C-l-b): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Cg alkoxy, Ci-Cg alkyl-Ci-Cg alkoxy, Ci-Cg alkyl-NR^Ci-Cg alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-Cg alkyl, -S(O)2NR3R4, and -S(O)2Ci-Cg alkyl; and all other variables are as defined herein.

[0128] In some embodiments, the compound is of Formula (A-l-a-I-C-l-b-I): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Cg alkoxy, Ci-Ce alkyl-Ci-Cg alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0129] In some embodiments, the compound is of Formula (A-l-a-I-C-l-b-II): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0. 1, 2, 3, 4, 5, 6, 7, 8, 9. and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NRkCi-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0130] In some embodiments, the compound is of Formula (A-l-a-I-C-l-c): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Cg alkoxy, Ci-Cg alkyl-Ci-Cg alkoxy, Ci-Cg alkyl-NR^Ci-Cfi alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-Cg alkyl, -S(O)2NR3R4, and -S(O)2Ci-Cg alkyl; and all other variables are as defined herein.

[0131] In some embodiments, the compound is of Formula (A-l-a-I-C-l-c-I): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Cg alkoxy, Ci-Cg alkyl-Ci-Cg alkoxy, Ci-Cg alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-Cg alkyl, -S(O)2NR3R4, and -S(O)2Ci-Cg alkyl; and all other variables are as defined herein.

[0132] In some embodiments, the compound is of Formula (A-l-a-I-C-l-c-II): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Cs alkoxy, Ci-Ce alkyl-NR^Ci-Cfi alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0133] In some embodiments, the compound is of Formula (A-l-a-I-C-l-c-III): I R5               (A-l-a-I-C-l-c-III), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Cg alkoxy, Ci-Cg alkyl-Ci-Cg alkoxy, Ci-Cg alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0134] In some embodiments, the compound is of Formula (A-l-a-I-C-2): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0. 1. 2. 3.4. 5. 6. 7. 8. 9. and 10; f is an integer selected from 1, 2, and 3; g is an integer selected from 1, 2, and 3; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-Ce alkyl, -S(O)2NR3R4, and -S(O)2Ci-Ce alkyl; and all other variables are as defined herein.

[0135] In some embodiments, the compound is of Formula (A-l-a-I-C-2-a): HN^ । / N-Y I R5                  (A-l-a-I-C-2-a), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cs alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0136] In some embodiments, the compound is of Formula (A-l-a-I-C-2-a-I): I R5                      (A-l-a-I-C-2-a-I), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other vanables are as defined herein.

[0137] In some embodiments, the compound is of Formula (A-l-a-I-C-2-a-II): I R5               (A-l-a-I-C-2-a-II), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NRkCi-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0138] In some embodiments, the compound is of Formula (A-l-a-I-C-2-a-III): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cs alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0139] In some embodiments, the compound is of Formula (A-l-a-I-C-3): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; f is an integer selected from 1,2, and 3; g is an integer selected from 1, 2, and 3; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-Cc alkyl, -S(O)2NR3R4, and -S(O)2Ci-Ce alkyl; and all other variables are as defined herein.

[0140] In some embodiments, the compound is of Formula (A-l-a-I-C-3-a): °\ I / N~Y I R5                  (A-l-a-I-C-3-a), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other vanables are as defined herein.

[0141] In some embodiments, the compound is of Formula (A-l-a-I-C-3-a-I): O\ ।    -----Y I R5                      (A-l-a-I-C-3-a-I), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Cs alkoxy, Ci-Ce alkyl-NRkCi-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0142] In some embodiments, the compound is of Formula (A-l-a-I-C-3-a-II): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cs alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0143] In some embodiments, the compound is of Formula (A-l-a-I-D): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein Ring D is 5-10 membered monocyclic or bicyclic heteroaryl comprising 1-3 heteroatoms selected from N, O, S; W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected fromH, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Cg alkoxy, Ci-C6 alkyl-NRkCi-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-Cs alkyl and all other variables are as defined herein.

[0144] In some embodiments, the compound is of Formula (A-l-a-I-D-1): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cs alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl and all other variables are as defined herein.

[0145] In some embodiments, the compound is of Formula (A-l-a-I-D-l-a): (A-l-a-I-D-l-a), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl and all other vanables are as defined herein.

[0146] In some embodiments, the compound is of Formula (A-l-a-I-D-l-b): "N             (A-l-a-I-D-l-b), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cs alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl and all other variables are as defined herein.

[0147] In some embodiments, the compound is of Formula (A-l-b-I): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein Ring A is selected from Cs-Cio-cycloalkane, arene, heterocycle, heteroarene; W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-Ce alkyl, -S(O)2NR3R4, and -S(O)2Ci-Ce alkyl and all other variables are as defined herein.

[0148] In some embodiments, the compound is of Formula (A-l-b-I-A): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0,1, 2, 3,4, 5, 6, 7, 8, 9, and 10; v is an integer selected from 0, 1, 2, 3, 4 and 5; R5 is selected from H, halogen, OH, oxo, CN, C1-C6 alkyl, C1-C6 alkoxy, Ci-C6 alkyl-Ci-C6 alkoxy, Ci-C6 alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0149] In some embodiments, the compound is of Formula (A-l-b-I-A-1): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein v is an integer selected from 0, 1, 2, 3, 4 and 5; R5 is selected from H, halogen, OH, oxo, CN, Ci-C6 alkyl, Ci-C6 alkoxy, Ci-C6 alkyl-Ci-C6 alkoxy, Ci-C6 alkyl-NR^Ci-Cg alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0150] In some embodiments, the compound is of Formula (A-l-b-I-B): R5                      (A-l-b-I-B), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Cs alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl and all other variables are as defined herein.

[0151] In some embodiments, the compound is of Formula (A-l-b-I-B-0): R5                      (A-l-b-I-B-0), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Cg alkoxy, Ci-Cg alkyl-Ci-Cs alkoxy, Ci-C6 alkyl-NR^Ci-Cg alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl and all other variables are as defined herein.

[0152] In some embodiments, the compound is of Formula (A-l-b-I-B-1): R5                      (A-l-b-I-B-1), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Cg alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl and all other variables are as defined herein.

[0153] In some embodiments, the compound is of Formula (A-l-b-I-B-2): R5                  (A-l-b-I-B-2), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Cs alkoxy, Ci-Ce alkyl-NRkCi-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl and all other variables are as defined herein.

[0154] In some embodiments, the compound is of Formula (A-l-b-I-B-3): I R5               (A-l-b-I-B-3), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl-Ci-C6 alkoxy, C1-C6 alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl and all other variables are as defined herein.

[0155] In some embodiments, the compound is of Formula (A-l-b-I-C): R5            (A-l-b-I-C), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein Ring His 3-10 membered monocyclic or bicyclic heterocycle comprising 1-3 heteroatoms selected from N, O, S; W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected fromH, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Cg alkoxy, Ci-C6 alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-G, alkyl and all other variables are as defined herein.

[0156] In some embodiments, the compound is of Formula (A-l-b-I-C-1): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0,1, 2, 3,4, 5, 6, 7, 8, 9, and 10; v is an integer selected from 0, 1, 2, 3, 4 and 5; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Cg alkoxy, Ci-C6 alkyl-Ci-C6 alkoxy, Ci-C6 alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-Ce alkyl; and all other variables are as defined herein.

[0157] In some embodiments, the compound is of Formula (A-l-b-I-C-l-a): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Cs alkoxy, Ci-Ce alkyl-NRCCi-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0158] In some embodiments, the compound is of Formula (A-l-b-I-C-l-a-I): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cs alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0159] In some embodiments, the compound is of Formula (A-l-b-I-C-l-a-II): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Cs alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0160] In some embodiments, the compound is of Formula (A-l-b-I-C-l-b): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0161] In some embodiments, the compound is of Formula (A-l-b-I-C-l-b-I): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(0)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0162] In some embodiments, the compound is of Formula (A-l-b-I-C-l-b-II): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cs alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(0)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0163] In some embodiments, the compound is of Formula (A-l-b-I-C-l-c): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other vanables are as defined herein.

[0164] In some embodiments, the compound is of Formula (A-l-b-I-C-l-c-I): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Cg alkoxy, Ci-Cg alkyl-Ci-Cg alkoxy, Ci-Cg alkyl-NR^Ci-Cfi alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-Cg alkyl, -S(O)2NR3R4, and -S(O)2Ci-Cg alkyl; and all other variables are as defined herein.

[0165] In some embodiments, the compound is of Formula (A-l-b-I-C-l-c-II): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Cg alkoxy, Ci-Cg alkyl-Ci-Cg alkoxy, Ci-Cg alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-Cg alkyl, -S(O)2NR3R4, and -S(O)2Ci-Cg alkyl; and all other variables are as defined herein.

[0166] In some embodiments, the compound is of Formula (A-l-b-I-C-l-c-III): R5               (A-l-b-I-C-l-c-III), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Cs alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0167] In some embodiments, the compound is of Formula (A-l-b-I-C-2): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; f is an integer selected from 1,2, and 3; g is an integer selected from 1, 2, and 3; R5 is selected from H, halogen, OH, oxo, CN, Ci-C6 alkyl, Ci-Cg alkoxy, Ci-Cg alkyl-Ci-Cg alkoxy, Ci-Cg alkyl-NR^Ci-Cg alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-Ce alkyl, -S(O)2NR3R4, and -S(O)2Ci-Cs alkyl; and all other variables are as defined herein.

[0168] In some embodiments, the compound is of Formula (A-l-b-I-C-2-a): HN । N-Y I R5                  (A-l-b-I-C-2-a), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other vanables are as defined herein.

[0169] In some embodiments, the compound is of Formula (A-l-b-I-C-2-a-I): I R5                      (A-l-b-I-C-2-a-I), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Cs alkoxy, Ci-Ce alkyl-NRkCi-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0170] In some embodiments, the compound is of Formula (A-l-b-I-C-2-a-II): I R5               (A-l-b-I-C-2-a-II), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cs alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(0)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0171] In some embodiments, the compound is of Formula (A-l-b-I-C-2-a-III): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NRkCi-C6 alkyl, NR3R4, -C(O)NR3R4, -S(0)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0172] In some embodiments, the compound is of Formula (A-l-b-I-C-3): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0. 1. 2. 3.4. 5. 6. 7. 8. 9. and 10; f is an integer selected from 1, 2, and 3; g is an integer selected from 1, 2, and 3; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-Ce alkyl, -S(O)2NR3R4, and -S(O)2Ci-Ce alkyl; and all other variables are as defined herein.

[0173] In some embodiments, the compound is of Formula (A-l-b-I-C-3-a): I R5                  (A-l-b-I-C-3-a), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cs alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0174] In some embodiments, the compound is of Formula (A-l-b-I-C-3-a-I): I R5                      (A-l-b-I-C-3-a-I), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other vanables are as defined herein.

[0175] In some embodiments, the compound is of Formula (A-l-b-I-C-3-a-II): I R5               (A-l-b-I-C-3-a-II), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NRkCi-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl; and all other variables are as defined herein.

[0176] In some embodiments, the compound is of Formula (A-l-b-I-D): R5            (A-l-b-I-D), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein Ring D is 5-10 membered monocyclic or bicyclic heteroaryl comprising 1-3 heteroatoms selected from N, O, S; W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected fromH, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Cs alkoxy, Ci-C6 alkyl-NRkCi-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-G, alkyl and all other variables are as defined herein.

[0177] In some embodiments, the compound is of Formula (A-l-b-I-D-1): or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Cs alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl and all other variables are as defined herein.

[0178] In some embodiments, the compound is of Formula (A-l-b-I-D-l-a): N^NZ           (A-l-b-I-D-l-a), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Cs alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl and all other variables are as defined herein.

[0179] In some embodiments, the compound is of Formula (A-l-b-I-D-l-b): N^NZ           (A-l-b-I-D-l-b), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl and all other vanables are as defined herein.

[0180] In some embodiments, the compound is of Formula (A-B): R5 (A-B), or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein Ring A is selected from Cs-Cio-cycloalkane, arene, heterocycle, heteroarene; W is (CH2)W; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R5 is selected from H, halogen, OH, oxo, CN, Ci-C6 alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-Ce alkyl, -S(O)2NR3R4, and -S(O)2Ci-Cs alkyl; u is an integer selected from 0 and 1; and all other variables are as defined herein.

[0181] In more specific aspect, the present disclosure provides compounds of Formula (I) and salts, stereoisomers, solvates, prodrugs, isotopic derivatives, and tautomers thereof: Wherein Ra, Rb, Rc, Rd, X, L1, Y, L2, and Z are as described herein.

[0182] It is understood that, for a compound of Formula (I), Ra, Rb, Rc, Rd, X, L1, Y, L2, and Z can each be, where applicable, selected from the groups described herein, and any group described herein for any Ra, Rb, Rc, Rd, X, L1, Y, L2, and Z can be combined, where applicable, with any group described herein for one or more of the remainder of Ra, Rb, Rc, Rd, X, L1, Y, L2, and Z.

[0183] In some embodiments, the compound is of Formula (I) wherein Ra is selected from H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, =0, NR3R4, CN, NO2, COOR1, CONR3R4; Rb, Rc, Rd are each independently selected from H, halogen, OH, NH2, CN, NO2, Ci-Cs alkyl, and Ci-Ce alkoxy, wherein alkyl or alkoxy is optionally substituted with one or more halogen, CN; X is selected from a bond, O, NR1, C(R2)2, S, S(0), S(0)2, C(0), C(0)0, C(O)NR1, 0C(0)0, N(R2)C(O)NR2, arenediyl; R1 is selected from H, Ci-Ce alkyl, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Ci-Ce acyl, heterocycle, aryl, heteroaryl, and S(O)2R2 wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, Ci-Ce alkyl, Ci-Ce alkoxy, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, heteroaryl; each R2 is independently selected from H, Ci-Cs alkyl, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, and heteroaryl wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, Ci-Ce alkyl, Ci-Ce alkoxy, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, heteroaryl; Y is selected from a bond, 0, NR1, C(R2)2, S, S(0), S(0)2, C(0), C(0)0, C(0)NR1, 0C(0)0, N(R2)C(O)NR2; Z is selected from a bond, 0, C(R2)2; L1 is selected from heterocyclediyl-Ci-Cio-alkanediyl, C1-C10 alkanediyl, C2-C10 alkenediyl, C2-C10 alkynediyl, C3-Cio-cycloalkanediyl, C3-Cio-cycloalkanediyl-Ci-Cio-alkanediyl, arenediyl, arenediyl-Ci-Cw-alkanediyl, heterocyclediyl, heterocyclediyl-C(O), heteroarenediyl, heteroarenediyl-Ci-Cio alkanediyl, Ci-Ce alkanediyl-O-Ci-Ce alkanediyl, Ci-Ce alkanediyl-NR1- Ci-Ce alkanediyl, Ci-Ce alkanediyl-C(0)NR1-Ci-C6 alkanediyl, wherein alkanediyl, alkendiyl, alkynediyl, arenediyl, heterocyclediyl or heteroarenediyl heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-C6 alkyl-Ci-C6 alkoxy, Ci-C6 alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2Ci-C6 alkyl; L2 is selected from C1-C10 alkanediyl, C2-Cio alkenediyl, C2-Cio alkynediyl, C3-C10-cycloalkanediyl, Cs-Cio-cycloalkanediyl-Ci-Cio-alkanediyl, arenediyl, arenediyl-Ci-Cio-alkanediyl, heterocyclediyl, heterocyclediyl-Ci-Cio-alkanediyl, heterocyclediyl-C(O), heteroarenediyl, heteroarenediyl-Ci-Cio alkanediyl, Ci-Cs alkanediyl-O-Ci-Ce alkanediyl, Ci-Ce alkanediyl-NR'-Ci-Ce alkanediyl, Ci-Ce alkanediyl-CCOlNR^Ci-Ce alkanediyl, wherein alkanediyl, alkendiyl, alkynediyl, arenediyl, heterocyclediyl or heteroarenediyl heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, Ci-Ce alkyd, Ci-Ce alkoxy, Ci-Cs alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR'-Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2Ci-C6 alkyl; R3 and R4 are each independently selected from H, Ci-Ce alkyl, Ci-Ce acyl and C3-C10 cycloalkyl; or R3 and R4 together with the atoms to which they are attached and any intervening atoms, form a 5-14 membered heterocycle, wherein the heterocycle is optionally substituted with one or more substituents independently selected from halogen, OH, =0, CN, NO2, Ci-Ce alkyl, Ci-Cs alkoxy.

[0184] In another more specific aspect, the present disclosure provides compounds of Formula (II) and salts, stereoisomers, solvates, prodrugs, isotopic derivatives, and tautomers thereof: L1-----Y----L2 (II), Wherein Ra, Rb, Rc, Rd, X, L1, Y, L2, and Z are as described herein.

[0185] It is understood that, for a compound of Formula (I), Ra, Rb, Rc, Rd, X, L1, Y, L2, and Z can each be, where applicable, selected from the groups described herein, and any group described herein for any Ra, Rb, Rc, Rd, X, L1, Y, L2, and Z can be combined, where applicable, with any group described herein for one or more of the remainder of Ra, Rb, Rc, Rd, X, L1, Y, L2, and Z.

[0186] In some embodiments, the compound is of Formula (II) L1-----Y----L2 (ii), wherein Ra is selected from H, Ci-Ce alkyl, C2-Ce alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, =0, NR3R4, CN, NO2, COOR1, CONR3R4; Rb, Rc, Rd are each independently selected from H, halogen, OH, NH2, CN, NO2, Ci-Cs alkyl, and Ci-Ce alkoxy, wherein alkyl or alkoxy is optionally substituted with one or more halogen, CN; X is selected from a bond, O, NR1, C(R2)2, S, S(O), S(O)2, C(O), C(O)O, C(O)NR1, OC(O)O, N(R2)C(O)NR2, arenediyl; R1 is selected from H, Ci-Ce alkyl, C3-C10 cycloalkyl, C2-Cs alkenyl, C2-Cs alkynyl, Ci-Ce acyl, heterocycle, aryl, heteroaryl, and S(O)2R2 wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, Ci-Ce alkyl, Ci-Ce alkoxy, C3-C10 cycloalkyl, C2-Ce alkenyl, C2-C6 alkynyl, heterocycle, aryl, heteroaryl; each R2 is independently selected from H, Ci-Ce alkyl, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-Ce alkynyl, heterocycle, aryl, and heteroaryl wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, Ci-Ce alkyl, Ci-Ce alkoxy, C3-C10 cycloalkyl, C2-Ce alkenyl, C2-Cg alkynyl, heterocycle, aryl, heteroaryl; Y is selected from a bond, O, NR1, C(R2)2, S, S(0), S(0)2, C(0), C(0)0, C(O)NR1, 0C(0)0, N(R2)C(O)NR2; Z is selected from a bond, 0, C(R2)2; L1 is selected from heterocyclediyl-Ci-Cio-alkanediyl, C1-C10 alkanediyl, C2-C10 alkenediyl, C2-Cio alkynediyl, C3-Cio-cycloalkanediyl, C3-Cio-cycloalkanediyl-Ci-Cio-alkanediyl, arenediyl, arenediyl-Ci-Cio-alkanediyl, heterocyclediyl, heterocyclediyl-C(O), heteroarenediyl, heteroarenediyl-Ci-Cio alkanediyl, Ci-Ce alkanediyl-O-Ci-Ce alkanediyl, Ci-Ce alkanediyl-NR1-Ci-Ce alkanediyl, Ci-Ce alkanediyl-C^NR^Ci-Ce alkanediyl, wherein alkanediyl, alkendiyl, alkynediyl, arenediyl, heterocyclediyl or heteroarenediyl heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-C6 alkyl-Ci-C6 alkoxy, Ci-C6 alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, aiyl, and -S(O)2Ci-C6 alkyl; L2 is selected from C1-C10 alkanediyl, C2-C10 alkenediyl, C2-Cio alkynediyl, C3-C10-cycloalkanediyl, Cs-Cio-cycloalkanediyl-Ci-Cio-alkanediyl, arenediyl, arenediyl-Ci-Cio-alkanediyl, heterocyclediyl, heterocyclediyl-Ci-Cio-alkanediyl, heterocyclediyl-C(O), heteroarenediyl, heteroarenediyl-Ci-Cio alkanediyl, Ci-Ce alkanediyl-O-Ci-Ce alkanediyl, Ci-Ce alkanediyl-NR'-Ci-Ce alkanediyl, Ci-Ce alkanediyl-C(O)NR1-Ci-Ce alkanediyl, wherein alkanediyl, alkendiyl, alkynediyl, arenediyl, heterocyclediyl or heteroarenediyl heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR1-Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2Ci-C6 alkyl; R3 and R4 are each independently selected from H, Ci-Ce alkyl, Ci-Ce acyl and C3-C10 cycloalkyl; or R3 and R4 together with the atoms to which they are attached and any intervening atoms, form a 5-14 membered heterocycle, wherein the heterocycle is optionally substituted with one or more substituents independently selected from halogen, OH, =0, CN, NO2, Ci-Ce alkyl, Ci-Ce alkoxy.

[0187] In some embodiments, Ra is selected from H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, =0, NR3R4, CN, N02, COOR1, CONR3R4.

[0188] In some embodiments, Ra is H.

[0189] In some embodiments, Ra is Ci-Ce alkyl.

[0190] In some embodiments, Ra is C1-C6 alkyl substituted with one or more halogen.

[0191] In some embodiments, Ra is Ci-Ce alkyl substituted with one or more F.

[0192] In some embodiments, Ra is -CH3.

[0193] In some embodiments, Ra is -CH2CH3.

[0194] In some embodiments, Ra is -CH2F.

[0195] In some embodiments, Ra is -CHF2.

[0196] In some embodiments, Ra is -CF3.

[0197] In some embodiments, Ra is -CH2CHF2.

[0198] In some embodiments, Ra is C2-C6 alkenyl.

[0199] In some embodiments, Ra is -CH2CH=CH2.

[0200] In some embodiments, Rb is selected from H, halogen, OH, NH2, CN, NO2, Ci-Ce alkyl, and Ci-Ce alkoxy, wherein alkyl or alkoxy is optionally substituted with one or more halogen, CN.

[0201] In some embodiments, Rb is H.

[0202] In some embodiments, Rb is halogen.

[0203] In some embodiments, Rb is F.

[0204] In some embodiments, Rb is Cl.

[0205] In some embodiments, Rb is Br.

[0206] In some embodiments, Rb is OH.

[0207] In some embodiments, Rb is CN.

[0208] In some embodiments, Rb is CF3.

[0209] In some embodiments, Rc is selected from H, halogen, OH, NH2, CN, NO2, Ci-Ce alkyl, and Ci-Ce alkoxy, wherein alkyl or alkoxy is optionally substituted with one or more halogen, CN.

[0210] In some embodiments, Rc is H.

[0211] In some embodiments, Rc is halogen.

[0212] In some embodiments, Rc is F.

[0213] In some embodiments, Rc is Cl.

[0214] In some embodiments, Rc is Br.

[0215] In some embodiments, Rc is OH.

[0216] In some embodiments, Rc is CN.

[0217] In some embodiments, Rc is CF3.

[0218] In some embodiments, Rd is selected from H, halogen, OH, NH2, CN, NO2, Ci-Ce alkyl, and Ci-Ce alkoxy, wherein alkyl or alkoxy is optionally substituted with one or more halogen, CN.

[0219] In some embodiments, Rd is H.

[0220] In some embodiments, Rd is halogen.

[0221] In some embodiments, Rd is F.

[0222] In some embodiments, Rd is Cl.

[0223] In some embodiments, Rd is Br.

[0224] In some embodiments, Rd is OH.

[0225] In some embodiments, Rd is CN.

[0226] In some embodiments, Rd is CF3.

[0227] In some embodiments, the Compound is of Formula (I-A) L1----Y----L2 (LA), wherein X is selected from O, a bond, NR1, C(R2)2, S, S(O), S(O)2, C(O), C(O)O, C(O)NR1, OC(O)O, N(R2)C(O)NR2, arenediyl; R1 is selected from H, Ci-Ce alkyl, C3-C10 cycloalkyl, C2-Ce alkenyl, C2-Ce alkynyl, Ci-Cs acyl, heterocycle, aryl, heteroaryl, and S(O)2R2 wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, Ci-Ce alkyl, Ci-Ce alkoxy, C3-C10 cycloalkyl, C2-Ce alkenyl, C2-Cg alkynyl, heterocycle, aryl, heteroaryl; each R2 is independently selected from H, Ci-Cs alkyl, C3-C10 cycloalkyl, C2-Ce alkenyl, C2-Ce alkynyl, heterocycle, aryl, and heteroaryl wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, Ci-Ce alkyl, Ci-Ce alkoxy, C3-C10 cycloalkyl, C2-Ce alkenyl, C2-C6 alkynyl, heterocycle, aryl, heteroaryl; Y is selected from a bond, O, NR1, C(R2)2, S, S(0), S(0)2, C(0), C(0)0, C(0)NR1, 0C(0)0, N(R2)C(O)NR2; Z is selected from a bond, 0, C(R2)2; L1 is selected from heterocyclediyl-Ci-Cio-alkanediyl, C1-C10 alkanediyl, C2-Cio alkenediyl, C2-Cio alkynediyl, C3-Cio-cycloalkanediyl, C3-Cio-cycloalkanediyl-Ci-Cio-alkanediyl, arenediyl, arenediyl-Ci-Cio-alkanediyl, heterocyclediyl, heterocyclediyl-C(O), heteroarenediyl, heteroarenediyl-Ci-Cio alkanediyl, Ci-Ce alkanediyl-O-Ci-Ce alkanediyl, Ci-Ce alkanediyl-NR1-Ci-Cg alkanediyl, Ci-Cg alkanediyl-C(0)NR1-Ci-C6 alkanediyl, wherein alkanediyl, alkendiyl, alkynediyl, arenediyl, heterocyclediyl or heteroarenediyl heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-C6 alkyl-Ci-C6 alkoxy, Ci-C6 alkyl-NR^Ci-Cg alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-Ce alkyl, -S(O)2NR3R4, aryl, and -S(O)2Ci-C6 alkyl; L2 is selected from C1-C10 alkanediyl, C2-C10 alkenediyl, C2-Cio alkynediyl, C3-C10-cycloalkanediyl, Cs-Cio-cycloalkanediyl-Ci-Cio-alkanediyl, arenediyl, arenediyl-Ci-Cio- alkanediyl, heterocyclediyl, heterocyclediyl-Ci-Cw-alkanediyl, heterocyclediyl-C(O), heteroarenediyl, heteroarenediyl-C1-C10 alkanediyl, Ci-Ce alkanediyl-O-Ci-Cg alkanediyl, Ci-Ce alkanediyl-NR'-Ci-Ce alkanediyl, Ci-Ce alkanediyl-C(O)NR1-Ci-Cg alkanediyl, wherein alkanediyl, alkendiyl, alkynediyl, arenediyl, heterocyclediyl or heteroarenediyl heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Cs alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2Ci-C6 alkyl; R3 and R4 are each independently selected from H, Ci-Ce alkyl, Ci-Ce acyl and C3-C10 cycloalkyl; or R3 and R4 together with the atoms to which they are attached and any intervening atoms, form a 5-14 membered heterocycle, wherein the heterocycle is optionally substituted with one or more substituents independently selected from halogen, OH, =0, CN, N02, Ci-Ce alkyl, Ci-Ce alkoxy.

[0228] In some embodiments, the Compound is of Formula (II-A) L1----Y----L2 (II-A), wherein X is selected from 0, a bond, NR1, C(R2)2, S, S(0), S(0)2, C(0), C(0)0, C(0)NR3, 0C(0)0, N(R2)C(O)NR2, arenediyl; R1 is selected from H, Ci-Cg alkyl, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Ci-Ce acyl, heterocycle, aryl, heteroaryl, and S(O)2R2 wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, Ci-Ce alkyl, Ci-Ce alkoxy, C3-C10 cycloalkyl, C2-Ce alkenyl, C2-Cg alkynyl, heterocycle, aryl, heteroaryl; each R2 is independently selected from H, Ci-Cg alkyl, C3-C10 cycloalkyl, C2-Cg alkenyl, C2-Cg alkynyl, heterocycle, aryl, and heteroaryl wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, Ci-Ce alkyl, Ci-Ce alkoxy, C3-C10 cycloalkyl, C2-Cg alkenyl, C2-C6 alkynyl, heterocycle, aryl, heteroaryl; Y is selected from a bond, O, NR1, C(R2)2, S, S(O), S(O)2, C(O), C(O)O, C(O)NR\ OC(O)O, N(R2)C(O)NR2; Z is selected from a bond, O, C(R2)2; L1 is selected from heterocyclediyl-Ci-Cio-alkanediyl, Ci-Cio alkanediyl, C2-Cio alkenediyl, C2-C10 alkynediyl, C3-Cio-cycloalkanediyl, C3-Cio-cycloalkanediyl-Ci-Cio-alkanediyl, arenediyl, arenediyl-Ci-Cio-alkanediyl, heterocyclediyl, heterocyclediyl-C(O), heteroarenediyl, heteroarenediyl-Ci-Cio alkanediyl, Ci-Cg alkanediyl-O-Ci-Cg alkanediyl, Ci-Cg alkanediyl-NR1-Ci-Ce alkanediyl, Ci-Ce alkanediyl-C(0)NR1-Ci-C6 alkanediyl, wherein alkanediyl, alkendiyl, alkynediyl, arenediyl, heterocyclediyl or heteroarenediyl heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-C6 alkyl-Ci-C6 alkoxy, Ci-C6 alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2Ci-C6 alkyl; L2 is selected from C1-C10 alkanediyl, C2-Cio alkenediyl, C2-Cio alkynediyl, C3-C10-cycloalkanediyl, Cs-Cw-cycloalkanediyl-Ci-Cio-alkanediyl, arenediyl, arenediyl-Ci-Cio-alkanediyl, heterocyclediyl, heterocyclediyl-Ci-Cio-alkanediyl, heterocyclediyl-C(O), heteroarenediyl, heteroarenediyl-Ci-Cio alkanediyl, Ci-Ce alkanediyl-O-Ci-Ce alkanediyl, Ci-Ce alkanediyl-NR'-Ci-Ce alkanediyl, Ci-Ce alkanediyl-C(0)NR1-Ci-C6 alkanediyl, wherein alkanediyl, alkendiyl, alkynediyl, arenediyl, heterocyclediyl or heteroarenediyl heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Cg alkyl-Ci-Cg alkoxy, Ci-Cg alkyl-NR^Cr-Cg alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2Ci-C6 alkyl; R3 and R4 are each independently selected from H, Ci-Ce alkyl, Ci-Ce acyl and C3-C10 cycloalkyl; or R3 and R4 together with the atoms to which they are attached and any intervening atoms, form a 5-14 membered heterocycle, wherein the heterocycle is optionally substituted with one or more substituents independently selected from halogen, OH, =0, CN, N02, Ci-Cg alkyl, Ci-Cg alkoxy.

[0229] In some embodiments, X is selected from a bond, 0, NR1, C(R2)2, S, S(0), S(0)2, C(0), C(0)0, C(O)NR1, 0C(0)0, orN(R2)C(O)NR2.

[0230] In some embodiments, X is a bond.

[0231] In some embodiments, X is a single bond.

[0232] In some embodiments, X is -0-. zR1 4 N 1

[0233] In some embodiments, X is ।    . 5 N i

[0234] In some embodiments, X is • xCH3 5 N i

[0235] In some embodiments, X is • Xy R2 ? ?x^r2 JV\

[0236] In some embodiments, X is I xy H JV\

[0237] In some embodiments, X is I xy H s\^CH3 » / v\

[0238] In some embodiments, X is I CH3 S^^CHs JV\

[0239] In some embodiments, X is I

[0240] In some embodiments, X is -S-. O II

[0241] In some embodiments, X is . xc- 0 s^lUo I kA / X

[0242] In some embodiments, X is I O II

[0243] In some embodiments, X is

[0244] In some embodiments, X is

[0245] In some embodiments, X is

[0246] In some embodiments, X is R1 O o1

[0247] In some embodiments, X is          . O

[0248] In some embodiments, X is H . O

[0249] In some embodiments, X is O

[0250] In some embodiments, X is O

[0251] In some embodiments, X is CH3

[0252] In some embodiments, R1 is selected from H, Ci-Ce alkyl, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, Ci-Ce acyl, heterocycle, aryl, heteroaryl, or S(O)2R2 wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, Ci-Ce alkyl, Ci-Ce alkoxy, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, heteroaiyl.

[0253] In some embodiments, R1 is H.

[0254] In some embodiments, R1 is CH3.

[0255] In some embodiments, R2is selected from H, Ci-Ce alkyl, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, or heteroaryl wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, Ci-Ce alkyl, Ci-Ce alkoxy, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, heteroaryl.

[0256] In some embodiments, R2 is H.

[0257] In some embodiments, R2 is CH3.

[0258] In some embodiments, Y is a bond, O, NR1, C(R2)2, S, S(O), S(O)2; C(O); C(O)O, C(O)NR\ OC(O)O, N(R2)C(O)NR2, arenediyl

[0259] In some embodiments, Y is a bond.

[0260] In some embodiments, Y is a single bond.

[0261] In some embodiments, Y is -0-.

[0262] In some embodiments, Y is zH N i

[0263] In some embodiments, Y is ।

[0264] In some embodiments, Y is

[0265] In some embodiments, Y is

[0266] In some embodiments, Y is

[0267] In some embodiments, Y is x / w

[0268] In some embodiments, Y is x / W

[0269] In some embodiments, Y is x / v*

[0270] In some embodiments, Y is

[0271] In some embodiments, Y is -S-.

[0272] In some embodiments, Y is xc O o

[0273] In some embodiments, Y is I

[0274] In some embodiments, Y is

[0275] In some embodiments, Y is

[0276] In some embodiments, Y is

[0277] In some embodiments, Y is R1

[0278] In some embodiments, Y is

[0279] In some embodiments, Y is

[0280] In some embodiments, Y is -OC(O)O-.

[0281] In some embodiments, Y is N(R2)C(O)NR2. R2 R2 I I

[0282] In some embodiments, Y is O H   H I                        I

[0283] In some embodiments, Y is O

[0284] In some embodiments, Y is O

[0285] In some embodiments, Y is O

[0286] In some embodiments, Z is selected from a bond, O, or C(R2)2.

[0287] In some embodiments, Z is a bond.

[0288] Tn some embodiments, Z is a single bond.

[0289] In some embodiments, Z is -O-.

[0290] In some embodiments, Z is C(R2)2.

[0291] In some embodiments, Z is CH2.

[0292] In some embodiments, L1 is selected from C1-C10 alkanediyl, C2-C10 alkenediyl, C2-C10 alkynediyl, Cs-Cio-cycloalkanediyl, Cs-Cio-cycloalkanediyl-Ci-Cio-alkanediyl, arenediyl, arenediyl-Ci-Cio-alkanediyl, heterocyclediyl, heterocyclediyl-Ci-Cio-alkanediyl, heterocyclediyl-C(O), heteroarenediyl, heteroarenediyl-Ci-Cio alkanediyl, Ci-Ce alkanediyl-O-Ci-Cg alkanediyl, Ci-Ce alkanediyl-NR1-Ci-Ce alkanediyl, Ci-Ce alkanediyl-C(O)NR1-Ci-C6 alkanediyl, wherein alkanediyl, alkendiyl, alkynediyl, arenediyl, heterocyclediyl or heteroarenediyl heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, Ci-Ce alkyd, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR'-Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2Ci-C6 alkyl.

[0293] In some embodiments, L1 is C1-C10 alkanediyl.

[0294] In some embodiments, L1 is C1-C10 alkanediyl optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-C6 alkoxy, Ci-C6 alkyl-NR'-Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2Ci-C6 alkyl.

[0295] In some embodiments, L1 is methanediyl.

[0296] In some embodiments, L1 is ethanediyl.

[0297] In some embodiments, L1 is 1,1-ethanediyl.

[0298] In some embodiments, L1 is 1,2-ethanediyl.

[0299] In some embodiments, L1 is propanediyl.

[0300] In some embodiments, L1 is 1,3-propanediyl.

[0301] In some embodiments, L1 is 1-methylpropanediyl-1,3.

[0302] In some embodiments, L1 is 2-methylpropanediyl-l,3.

[0303] In some embodiments, L1 is butanediyl.

[0304] In some embodiments, L1 is 1,4-butanediyl.

[0305] In some embodiments, L1 is 2-methylbutanediyl-l,4.

[0306] In some embodiments, L1 is pentanediyl.

[0307] In some embodiments, L1 is 1,5-pentanediyl.

[0308] Tn some embodiments, L1 is 3-methylpentanediyl-l ,5.

[0309] In some embodiments, L1 is 2,3-dimethylpentanediyl-l,5.

[0310] In some embodiments, L1 is hexanediyL

[0311] In some embodiments, L1

[0312] Tn some embodiments, L1

[0313] In some embodiments, L1

[0314] In some embodiments, L1

[0315] In some embodiments, L1

[0316] In some embodiments, L1

[0317] In some embodiments, L1

[0318] In some embodiments, L1

[0319] In some embodiments, L1

[0320] In some embodiments, L1

[0321] In some embodiments, L1

[0322] In some embodiments, L1

[0323] In some embodiments, L1

[0324] In some embodiments, L1

[0325] In some embodiments, L1

[0326] In some embodiments, L1

[0327] In some embodiments, L1

[0328] In some embodiments, L1

[0329] In some embodiments, L1

[0330] In some embodiments, L1

[0331] In some embodiments, L1

[0332] In some embodiments, L1

[0333] In some embodiments, L1

[0334] In some embodiments, L1

[0335] In some embodiments, L1

[0336] In some embodiments, L1

[0337] In some embodiments, L1

[0338] In some embodiments, L1

[0339] In some embodiments, L1

[0340] In some embodiments, L1

[0341] In some embodiments, L1

[0342] In some embodiments, L1

[0343] Tn some embodiments, L1

[0344] In some embodiments, L1

[0345] In some embodiments, L1 is 1,6-hexanediyl. is 3-methylhexanediyl-l,6. is 3,4-dimethylhexanediyl-l,6. is C2-C10 alkenediyl. is E-C2-C10 alkenediyl. is Z-C2-C10 alkenediyl. is ethenediyl. is ethenediyl-1,2. is propenediyl. is propenediyl-1,3. is 2-methylpropenediyl-l,3 is butenediyl. is butene-l-diyl-1,4. is E-butene-1-diyl-1,4. is Z-butene-l-diyl-1,4. is butene-2-diyl-l,4. is £'-butene-2-diyl-l,4. is Z-butene-2-diyl-l,4. is 2-methylbutene-2-diyl-l,4. is A-2-methylbLitene-2-diyl-L4. is Z-2-methylbutene-2-diyl-l,4. is pentenediyl. is pentene-2-diyl-1,5. is E-pentene-2-diyl-l,5. is Z-pentene-2-diyl-l,5. is 2-methylpentene-2-diyl-l,5. is E-2-methylpentene-2-diyl-l,5. is Z-2-methylpentene-2-diyl-l,5. is 3-methylpentene-2-diyl-l,5. is / •.-S-mclhylpcnlcnc^-diyl-1.5. is Z-3-methylpentene-2-diyl-l,5. is 2,3-dimethylpenten-2-diyl-l,5. is / ?-2,3-dimethylpenten-2-diyl-l ,5. is Z-2,3-dimethylpenten-2-diyl-l,5. is hexenediyl.

[0346] In some embodiments, L1 is hexene-2-diyl-l,6.

[0347] Tn some embodiments, L1 is hexene-3-diyl-l,6.

[0348] In some embodiments, L1 is 3-methylhexen-3-diyl-l,6.

[0349] In some embodiments, L1 is E-S-methylhexen-S-diyl-1,6.

[0350] In some embodiments, L1 is Z-3-methylhexen-3-diyl-l,6.

[0351] In some embodiments, L1 is 3,4-dimethylhexen-3-diyl-l,6.

[0352] In some embodiments, L1 is £'-3,4-dimethylhexen-3-diyl-1,6.

[0353] In some embodiments, L1 is Z-3,4-dimethylhexen-3-diyl-l,6.

[0354] In some embodiments, L1 is C2-C10 alkynediyl.

[0355] In some embodiments, L1 is ethynediyl.

[0356] In some embodiments, L1 is propynediyl.

[0357] In some embodiments, L1 is propyne-l-diyl-1,3.

[0358] In some embodiments, L1 is 3-methylpropyne-l-diyl-l,3.

[0359] In some embodiments, L1 is Cs-Cio-cycloalkanediyl.

[0360] In some embodiments, L1 is

[0361] In some embodiments, L1 is

[0362] In some embodiments, L1 is

[0363] In some embodiments, L1 is

[0364] In some embodiments, L1 is

[0365] In some embodiments, L1 is

[0366] In some embodiments, L1 is

[0367] In some embodiments, L1 is

[0368] In some embodiments, L1 is

[0369] In some embodiments, L1 is

[0370] In some embodiments, L1 is

[0371] In some embodiments, L1 is

[0372] In some embodiments, L1 is

[0373] In some embodiments, L1 is

[0374] In some embodiments, L1 is

[0375] In some embodiments, L1 is Cs-Cio-cycloalkanediyl-Ci-Cio-alkanediyl.

[0376] In some embodiments, L1 is

[0377] In some embodiments, L1 is

[0378] In some embodiments, L1 is

[0379] In some embodiments, L1 is

[0380] In some embodiments, L1 is

[0381] In some embodiments, L1 is arenediyl.

[0382] In some embodiments, L1 is

[0383] In some embodiments, L1 is

[0384] In some embodiments, L1 is

[0385] In some embodiments, L1 is arenediyl-Ci-Cio-alkanediyl.

[0386] In some embodiments, L1 is arenediyl-methanediyl.

[0387] In some embodiments, L1 is arenediyl-ethanediyl.

[0388] In some embodiments, L1 is arenediyl-1,2-ethanediyl.

[0389] In some embodiments, L1 is arenediyl-propanediyl.

[0390] In some embodiments, L1 is arenediyl-1,3-propanediyl.

[0391] In some embodiments, L1 is arenediyl-butanediyl.

[0392] In some embodiments, L1 is arenediyl-1,4-butanediyl.

[0393] In some embodiments, L1 is arenediyl-pentanediyl

[0394] In some embodiments, L1 is arenediyl-hexanediyl.

[0395] In some embodiments, L1 is arenediyl-heptanediyl.

[0396] In some embodiments, L1 is arenediyl-octanediyl.

[0397] In some embodiments, L1 is arenediyl-nonanediyl.

[0398] In some embodiments, L1 is arenediyl-decanediyl.

[0399] In some embodiments, L1 is phenylen-Ci-Cio-alkanediyl.

[0400] In some embodiments, L1 is

[0401] In some embodiments, L1 is

[0402] In some embodiments, L1 is

[0403] In some embodiments, L1 is heterocyclediyl.

[0404] In some embodiments, L1 is 3-membered heterocyclediyl.

[0405] In some embodiments, L1 is 3-membered heterocyclediyl comprising N as a heteroatom.

[0406] In some embodiments, L1 is 4-membered heterocyclediyl.

[0407] In some embodiments, L1 is 4-membered heterocyclediyl comprising N as a heteroatom.

[0408] In some embodiments, L1 is

[0409] In some embodiments, L1 is

[0410] In some embodiments, L1 is

[0411] In some embodiments, L1 is

[0412] In some embodiments, L1 is 5-membered heterocyclediyl.

[0413] In some embodiments, L1 is 5-membered heterocyclediyl comprising N as a heteroatom.

[0414] In some embodiments, L1 is

[0415] In some embodiments, L1 is

[0416] In some embodiments, L1 is 6-membered heterocyclediyl.

[0417] In some embodiments, L1 is 6-membered heterocyclediyl comprising N as a heteroatom.

[0418] In some embodiments, L1 is piperidinediyl.

[0419] In some embodiments, L1 is

[0420] In some embodiments, L1 is

[0421] In some embodiments, L1 is

[0422] In some embodiments, L1 is

[0423] In some embodiments, L1 is

[0424] In some embodiments, L1 is '---'     .

[0425] In some embodiments, L1 is 7-membered heterocyclediyl.

[0426] In some embodiments, L1 is 7-membered heterocyclediyl comprising N as a heteroatom.

[0427] In some embodiments, L1 is heterocyclediyl-Ci-Cio-alkanediyl.

[0428] In some embodiments, L1 is heterocyclediyl-methanediyl.

[0429] In some embodiments, L1 is heterocyclediyl-ethanediyl.

[0430] In some embodiments, L1 is heterocyclediyl-l,2-ethanediyl.

[0431] In some embodiments, L1 is heterocyclediyl-propanediyl.

[0432] In some embodiments, L1 is heterocyclediyl-1,3-propanediyl.

[0433] In some embodiments, L1 is heterocyclediyl-butanediyl.

[0434] In some embodiments, L1 is heterocyclediyl-l,4-butanediyl.

[0435] In some embodiments, L1 is heterocyclediyl-pentanediyl.

[0436] In some embodiments, L1 is heterocyclediyl-hexanediyl.

[0437] In some embodiments, L1 is heterocyclediyl-heptanediyl.

[0438] In some embodiments, L1 is heterocyclediyl-octanediyl.

[0439] In some embodiments, L1 is heterocyclediyl-nonanediyl.

[0440] In some embodiments, L1 is heterocyclediyl-decanediyl.

[0441] In some embodiments, L1 is 3-membered heterocyclediyl-Ci-Cio-alkanediyl.

[0442] In some embodiments, L1 is 4-membered heterocyclediyl-Ci-Cio-alkanediyl.

[0443] In some embodiments, L1 is

[0444] In some embodiments, L1 is

[0445] In some embodiments, L1 is

[0446] In some embodiments, L1 is

[0447] In some embodiments, L1 is

[0448] In some embodiments, L1 is

[0449] In some embodiments, L1 is

[0450] In some embodiments, L1 is

[0451] In some embodiments, L1 is 5-membered heterocyclediyl-Ci-Cio-alkanediyl.

[0452] In some embodiments, L1 is

[0453] In some embodiments, L1 is

[0454] In some embodiments, L1 is 6-membered heterocyclediyl-Ci-Cio-alkanediyl.

[0455] In some embodiments, L1 is z

[0456] In some embodiments, L1 is

[0457] In some embodiments, L1 is

[0458] In some embodiments, L1 is

[0459] In some embodiments, L1 is

[0460] In some embodiments, L1 is

[0461] In some embodiments, L1 is

[0462] In some embodiments, L1 is

[0463] In some embodiments, L1 is

[0464] In some embodiments, L1 is

[0465] In some embodiments, L1 is

[0466] In some embodiments, L1 is

[0467] In some embodiments, L1 is '---'        .

[0468] In some embodiments, L1 is 7-membered heterocyclediyl-Ci-Cio-alkanediyl.

[0469] In some embodiments, L1 is heteroarenediyl.

[0470] In some embodiments, L1 is 5-membered heteroarenediyl.

[0471] In some embodiments, L1 is

[0472] In some embodiments, L1 is

[0473] In some embodiments, L1 is NO

[0474] In some embodiments, L1 is 6-membered heteroarenediyl.

[0475] In some embodiments, L1 is

[0476] In some embodiments, L1 is

[0477] In some embodiments, L1 is

[0478] In some embodiments, L1 is           .

[0479] In some embodiments, L1 is heteroarenediyl-Ci-Cio alkanediyl.

[0480] In some embodiments, L1 is heteroarenediyl-methanediyl.

[0481] In some embodiments, L1 is heteroarenediyl-ethanediyl.

[0482] In some embodiments, L1 is heteroarenediyl-1,2-ethanediyl.

[0483] In some embodiments, L1 is heteroarenediyl-propanediyl.

[0484] In some embodiments, L1 is heteroarenediyl-1,3-propanediyl.

[0485] In some embodiments, L1 is heteroarenediyl-butanediyl.

[0486] In some embodiments, L1 is heteroarenediyl-1,4-butanediyl.

[0487] In some embodiments, L1 is heteroarenediyl-pentanediyl.

[0488] Tn some embodiments, L1 is heteroarenediyl-hexanediyl.

[0489] In some embodiments, L1 is heteroarenediyl-heptanediyl.

[0490] In some embodiments, L1 is heteroarenediyl-octanediyl.

[0491] In some embodiments, L1 is heteroarenediyl-nonanediyl.

[0492] In some embodiments, L1 is heteroarenediyl-decanediyl.

[0493] In some embodiments, L1 is 5-membered heteroarenediyl-Ci-Cio alkanediyl.

[0494] In some embodiments, L1 is

[0495] In some embodiments, L1 is

[0496] In some embodiments, L1 is N-N N=N N=N

[0497] In some embodiments, L1 is N-0

[0498] In some embodiments, L1 is NO

[0499] In some embodiments, L1 is 6-membered heteroarenediyl-Ci-Cio alkanediyl.

[0500] In some embodiments, L1 is

[0501] In some embodiments, L1 is

[0502] In some embodiments, L1 is

[0503] In some embodiments, L1 is

[0504] In some embodiments, L1 is

[0505] Tn some embodiments, L1 is

[0506] In some embodiments, L1 is

[0507] In some embodiments, L1 is

[0508] In some embodiments, L1 is Ci-Ce alkanediyl-O-Ci-Ce alkanediyl.

[0509] In some embodiments, L1 is -CH2-O-CH2-.

[0510] In some embodiments, L1 is -CH2-O-CH2CH2-.

[0511] In some embodiments, L1 is -CH2-O-CH2CH2CH2-.

[0512] In some embodiments, L1 is -CH2CH2-O-CH2CH2-.

[0513] In some embodiments, L1 is -CH2CH2-O-CH2CH2CH2-.

[0514] In some embodiments, L1 is -CH2CH2CH2-O-CH2CH2CH2-.

[0515] In some embodiments, L1 is Ci-Ce alkanediyl-NR^Ci-Ce alkanediyl.

[0516] Tn some embodiments, L1 is Ci-Ce alkanediyl-NH-Ci-Ce alkanediyl.

[0517] In some embodiments, L1 is Ci-Ce alkanediyl-N(CH3)-Ci-C6 alkanediyl.

[0518] In some embodiments, L1 is

[0519] In some embodiments, L1 is

[0520] In some embodiments, L1 is

[0521] In some embodiments, L1 is Ci-Cs alkanediyl-C(O)NR1-Ci-Ce alkanediyl, wherein each alkanediyl is independently optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Cg alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2Ci-Ce alkyl.

[0522] Tn some embodiments, L1 is -CH2CH2CH2NHC(O)CH2- 0

[0523] In some embodiments, L1 is         H O

[0524] In some embodiments, L1 is             H O

[0525] In some embodiments, L1 is H               .

[0526] In some embodiments, L1 is -CH2CH2CH2NHC(O)C(CH3)H-. O H £

[0527] In some embodiments, L1 is                   =   .

[0529] In some embodiments, L1 is substituted with one or more substituents independently selected from halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Cg alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2Ci-Cs alkyl.

[0530] In some embodiments, L2 is selected from Ci-Cio alkanediyl, C2-C10 alkenediyl, C2-C10 alkynediyl, Cs-Cio-cycloalkanediyl, Cs-Cio-cycloalkanediyl-Ci-Cio-alkanediyl, arenediyl, arenediyl-Ci-Cio-alkanediyl, heterocyclediyl, heterocyclediyl-Ci-Cio-alkanediyl, heterocyclediyl-C(O), heteroarenediyl, heteroarenediyl-Ci-Cio alkanediyl, Ci-Ce alkanediyl-O-Ci-Ce alkanediyl, Ci-Ce alkanediyl-NRkCi-Ce alkanediyl, Ci-Ce alkanediyl-C(O)NR1-Ci-C6 alkanediyl, wherein alkanediyl, alkendiyl, alkynediyl, arenediyl, heterocyclediyl or heteroarenediyl heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, Ci-Ce alky l, Ci-Ce alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2Ci-C6 alkyl.

[0531] In some embodiments, L2 is C1-C10 alkanediyl.

[0532] In some embodiments, L2 is methanediyl.

[0533] In some embodiments, L2 is ethanediyl.

[0534] In some embodiments, L2 is 1,1-ethanediyl.

[0535] In some embodiments, L2 is 1,2-ethanediyl.

[0536] In some embodiments, L2 is propanediyl.

[0537] Tn some embodiments, L2 is 1,3-propanediyl.

[0538] In some embodiments, L2 is 1-methylpropanediyl-1,3.

[0539] In some embodiments, L2 is 2-methylpropanediyl-l,3.

[0540] In some embodiments, L2 is butanediyl.

[0541] In some embodiments, L2 is 1,3-butanediyl.

[0542] In some embodiments, L2 is 1,4-butanediyl.

[0543] In some embodiments, L2 is 2-methylbutanediyl-l,4.

[0544] In some embodiments, L2 is pentanediyl.

[0545] In some embodiments, L2 is 1,5-pentanediyl.

[0546] In some embodiments, L2 is 3-methylpentanediyl-l,5.

[0547] In some embodiments, L2 is 2,3-dimethylpentanediyl-l,5.

[0548] In some embodiments, L2 is hexanediyL

[0549] In some embodiments, L2 is 1,6-hexanediyl.

[0550] In some embodiments, L2 is 3-methylhexanediyl-l,6.

[0551] In some embodiments, L2 is 3,4-dimethylhexanediyl-l,6.

[0552] In some embodiments, L2 is C2-C10 alkenediyl.

[0553] In some embodiments, L2 is ethenediyl.

[0554] In some embodiments, L2is ethenediyl-1,2.

[0555] In some embodiments, L2 is propenediyl.

[0556] In some embodiments, L2is propenediyl-1,3.

[0557] In some embodiments, L2is 2-methylpropenediyl-l,3

[0558] In some embodiments, L2 is butenediyl.

[0559] In some embodiments, L2is butene-l-diyl-1,4.

[0560] In some embodiments, L2is E-butene-1-diyl-1,4.

[0561] In some embodiments, L2is Z-butene-l-diyl-1,4.

[0562] In some embodiments, L2is butene-2-diyl-l,4.

[0563] In some embodiments, L2 is £'-butene-2-diyl-l,4.

[0564] In some embodiments, L2 is Z-butene-2-diyl-l,4.

[0565] In some embodiments, L2is 2-methylbutene-2-diyl-l,4.

[0566] In some embodiments, L2is / / -2-inethylbutene-2-diyl-l .4.

[0567] In some embodiments, L2is Z-2-methylbutene-2-diyl-l,4.

[0568] Tn some embodiments, L2is pentenediyl.

[0569] In some embodiments, L2is pentene-2-diyl-1,5.

[0570] In some embodiments, L2is E-pentene^-diyl-l^.

[0571] In some embodiments, L2is Z-pentene-2-diyl-l,5.

[0572] Tn some embodiments, L2is 2-methylpentene-2-diyl-l,5.

[0573] In some embodiments, L2is E^-methylpentene^-diyl-l^.

[0574] In some embodiments, L2is Z-2-methylpentene-2-diyl-l,5.

[0575] In some embodiments, L2is 3-methylpentene-2-diyl-l,5.

[0576] In some embodiments, L2is E-S-methylpentene^-diyl-l^.

[0577] In some embodiments, L2is Z-3-methylpentene-2-diyl-l,5.

[0578] In some embodiments, L2is 2,3-dimethylpenten-2-diyl-l,5.

[0579] In some embodiments, L2is E^^-dimethylpenten^-diyl-l^.

[0580] In some embodiments, L2is Z-2,3-dimethylpenten-2-diyl-l,5.

[0581] In some embodiments, L2 is hexenediyl.

[0582] In some embodiments, L2 is hexene-2-diyl-l,6.

[0583] In some embodiments, L2 is hexene-3-diyl-l,6.

[0584] In some embodiments, L2is 3-methylhexen-3-diyl-l,6.

[0585] In some embodiments, L2is E-S-methylhexen-S-diyl-hb.

[0586] In some embodiments, L2 is Z-3-methylhexen-3-diyl-l,6.

[0587] In some embodiments, L2is 3,4-dimethylhexen-3-diyl-l,6.

[0588] In some embodiments, L2is E-3,4-dimethylhexen-3-diyl-1,6.

[0589] In some embodiments, L2is Z-3,4-dimethylhexen-3-diyl-l,6.

[0590] In some embodiments, L2 is C2-C10 alkynediyl.

[0591] In some embodiments, L2 is ethynediyl.

[0592] In some embodiments, L2 is propynediyl.

[0593] In some embodiments, L2 is propyne-l-diyl-1,3.

[0594] In some embodiments, L2 is 3-methylpropyne-l-diyl-l,3.

[0595] In some embodiments, L2is Cs-Cio-cycloalkanediyl.

[0596] In some embodiments, L2 is

[0597] In some embodiments, L2 is

[0598] In some embodiments, L2 is

[0599] In some embodiments, L2 is

[0600] In some embodiments, L2 is

[0601] In some embodiments, L2 is Cs-Cio-cycloalkanediyl-Ci-Cw-alkanediyl.

[0602] In some embodiments, L2 is

[0603] In some embodiments, L2 is

[0604] In some embodiments, L2 is

[0605] In some embodiments, L2 is

[0606] In some embodiments, L2 is arenediyl.

[0607] In some embodiments, L2 is

[0608] In some embodiments, L2 is

[0609] In some embodiments, L2 is

[0610] In some embodiments, L2 is arenediyl-Ci-Cio-alkanediyl.

[0611] In some embodiments, L2 is arenediyl-methanediyl.

[0612] In some embodiments, L2 is arenediyl-ethanediyl.

[0613] In some embodiments, L2 is arenediyl-1,2-ethanediyl.

[0614] In some embodiments, L2 is arenediyl-propanediyl.

[0615] In some embodiments, L2 is arenediyl-1,3-propanediyl.

[0616] In some embodiments, L2 is arenediyl-butanediyl.

[0617] Tn some embodiments, L2 is arenediyl -1,4-butanediyl.

[0618] In some embodiments, L2 is arenediyl-pentanediyl.

[0619] In some embodiments, L2 is arenediyl-hexanediyl.

[0620] In some embodiments, L2 is arenediyl-heptanediyl.

[0621] In some embodiments, L2 is arenediyl-octanediyl.

[0622] In some embodiments, L2 is arenediyl-nonanediyl.

[0623] In some embodiments, L2 is arenediyl-decanediyl.

[0624] In some embodiments, L2is phenylen-Ci-Cio-alkanediyl.

[0625] In some embodiments, L2 is

[0626] In some embodiments, L2 is

[0627] In some embodiments, L2 is J .

[0628] In some embodiments, L2 is heterocyclediyl.

[0629] In some embodiments, L2 is 3-membered heterocyclediyl.

[0630] In some embodiments, L2is 3-membered heterocyclediyl comprising N as a heteroatom.

[0631] In some embodiments, L2 is 4-membered heterocyclediyl.

[0632] In some embodiments, L2 is 4-membered heterocyclediyl comprising N as a heteroatom.

[0633] In some embodiments, L2 is 5-membered heterocyclediyl.

[0634] In some embodiments, L2is 5-membered heterocyclediyl comprising N as a heteroatom.

[0635] In some embodiments, L2 is 6-membered heterocyclediyl.

[0636] In some embodiments, L2 is 6-membered heterocyclediyl comprising N as a heteroatom.

[0637] In some embodiments, L2 is pipendinediyl.

[0638] In some embodiments, L2 is

[0639] In some embodiments, L2 is

[0640] In some embodiments, L2 is -^-N     N-£-

[0641] In some embodiments, L2 is \--- /    .

[0642] In some embodiments, L2 is 7-membered heterocyclediyl.

[0643] In some embodiments, L2is 7-membered heterocyclediyl comprising N as a heteroatom.

[0644] In some embodiments, L2 is heterocyclediyl-Ci-Cio-alkanediyl.

[0645] In some embodiments, L2 is heterocyclediyl-methanediyl.

[0646] In some embodiments, L2 is heterocyclediyl-ethanediyl.

[0647] In some embodiments, L2 is heterocyclediyl-l,2-ethanediyl.

[0648] In some embodiments, L2 is heterocyclediyl-propanediyl.

[0649] In some embodiments, L2 is heterocyclediyl-l,3-propanediyl.

[0650] In some embodiments, L2 is heterocyclediyl-butanediyl.

[0651] In some embodiments, L2 is heterocyclediyl-l,4-butanediyl.

[0652] In some embodiments, L2 is heterocyclediyl-pentanediyl.

[0653] In some embodiments, L2 is heterocyclediyl-hexanediyl.

[0654] In some embodiments, L2 is heterocyclediyl-heptanediyl.

[0655] In some embodiments, L2 is heterocyclediyl-octanediyl.

[0656] In some embodiments, L2 is heterocyclediyl-nonanediyl.

[0657] In some embodiments, L2 is heterocyclediyl-decanediyl.

[0658] In some embodiments, L2 is 3-membered heterocyclediyl-Ci-Cio-alkanediyl.

[0659] In some embodiments, L2 is 4-membered heterocyclediyl-Ci-Cio-alkanediyl.

[0660] In some embodiments, L2 is 5-membered heterocyclediyl-Ci-Cio-alkanediyl.

[0661] In some embodiments, L2 is 6-membered heterocyclediyl-Ci-Cio-alkanediyl.

[0662] In some embodiments, L2 is

[0663] In some embodiments, L2 is

[0664] In some embodiments, L2 is

[0665] In some embodiments, L2 is

[0666] In some embodiments, L2 is

[0667] In some embodiments, L2 is

[0668] In some embodiments, L2 is 7-membered heterocyclediyl-Ci-Cio-alkanediyl.

[0669] In some embodiments, L2 is heterocyclediyl-C(O).

[0670] In some embodiments, L2 is

[0671] In some embodiments, L2 is

[0672] In some embodiments, L2 is

[0673] In some embodiments, L2 is

[0674] In some embodiments, L2 is

[0675] In some embodiments, L2 is

[0676] In some embodiments, L2 is heteroarenediyl.

[0677] In some embodiments, L2 is 5-membered heteroarenediyl.

[0678] In some embodiments, L2 is

[0679] In some embodiments, L2 is N-N N=N

[0680] In some embodiments, L2 is NO

[0681] In some embodiments, L2 is 6-membered heteroarenediyl.

[0682] In some embodiments, L2 is

[0683] In some embodiments, L2 is

[0684] In some embodiments, L2 is i

[0685] In some embodiments, L2 is

[0686] In some embodiments, L2 is heteroarenediyl-Ci-Cio alkanediyl.

[0687] In some embodiments, L2 is heteroarenediyl-methanediyl.

[0688] In some embodiments, L2 is heteroarenediyl-ethanediyl.

[0689] In some embodiments, L2 is heteroarenediyl-1,2-ethanediyl.

[0690] In some embodiments, L2 is heteroarenediyl-propanediyl.

[0691] In some embodiments, L2 is heteroarenediyl-l,3-propanediyl.

[0692] In some embodiments, L2 is heteroarenediyl-butanediyl.

[0693] In some embodiments, L2 is heteroarenediyl-1,4-butanediyl.

[0694] In some embodiments, L2 is heteroarenediyl-pentanediyl.

[0695] In some embodiments, L2 is heteroarenediyl-hexanediyl.

[0696] In some embodiments, L2 is heteroarenediyl-heptanediyl.

[0697] In some embodiments, L2 is heteroarenediyl-octanediyl.

[0698] In some embodiments, L2 is heteroarenediyl-nonanediyl.

[0699] In some embodiments, L2 is heteroarenediyl-decanediyl.

[0700] In some embodiments, L2 is 5-membered heteroarenediyl-Ci-Cio alkanediyl.

[0701] In some embodiments, L2 is N-N

[0702] In some embodiments, L2 is

[0703] In some embodiments, L2 is

[0704] In some embodiments, L2 is N=N N=N N-0 N-0

[0705] In some embodiments, L2 is

[0706] In some embodiments, L2 is 6-membered heteroarenediyl-Ci-Cio alkanediyl.

[0707] In some embodiments, L2 is

[0708] In some embodiments, L2 is

[0709] In some embodiments, L2 is

[0710] In some embodiments, L2 is

[0711] In some embodiments, L2 is

[0712] In some embodiments, L2 is

[0713] In some embodiments, L2 is

[0714] In some embodiments, L2 is

[0715] In some embodiments, L2 is Ci-Ce alkanediyl-O-Ci-Ce alkanediyl.

[0716] In some embodiments, L2 is -CH2-O-CH2-.

[0717] In some embodiments, L2 is -CH2-O-CH2CH2-.

[0718] In some embodiments, L2 is -CH2-O-CH2CH2CH2-.

[0719] In some embodiments, L2 is -CH2CH2-O-CH2CH2-.

[0720] In some embodiments, L2 is -CH2CH2-O-CH2CH2CH2-.

[0721] In some embodiments, L2 is -CH2CH2CH2-O-CH2CH2CH2-.

[0722] In some embodiments, L2 is Ci-Ce alkanediyl-NR^Ci-Ce alkanediyl.

[0723] In some embodiments, L2 is Ci-Ce alkanediyl-NH-Ci-Ce alkanediyl.

[0724] In some embodiments, L2 is Ci-Ce alkanediyl-N(CH3)-Ci-C6 alkanediyl.

[0725] In some embodiments, L2 is Ci-Ce alkanediyl-C^NR^Ci-Ce alkanediyl.

[0726] In some embodiments, L2 is -CH2-NH-C(O)-CH2-.

[0727] In some embodiments, L2 is -CH2-N(CH3)-C(O)-CH2-.

[0728] In some embodiments, L2 is -CH2-CH2-NH-C(O)-CH2-.

[0729] In some embodiments, L2 is

[0730] In some embodiments, L2 is N H N H N H

[0731] In some embodiments, L2 is

[0732] In some embodiments, L2 is substituted with one or more substituents independently selected from halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Cg alkoxy, Ci-Ce alkyl-Ci-Ce alkoxy, Ci-Ce alkyl-NH-Ci-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl.

[0733] In some embodiments, RJ and R4 are each independently selected from H, Ci-Cg alkyl, Ci-Ce acyl and C3-C10 cycloalkyl.

[0734] In some embodiments, R3 and R4 are H.

[0735] In some embodiments, R3 is H and R4 is CH3.

[0736] Tn some embodiments, R3 and R4 are CH3.

[0737] In some embodiments, R3 and R4 together with the atoms to which they are attached and any intervening atoms, form a 5-14 membered heterocycle, wherein the heterocycle is optionally substituted with one or more substituents independently selected from halogen, OH, =0, CN, NO2, Ci-Cg alkyl, Ci-Cg alkoxy.

[0738] In some preferred embodiments, combination of X, Y, Z, L1, and L2 is selected from the Table 1

[0739] Table 1. Selection of possible values of X, Y, Z, L1, and L2. X L1 Y L2 z bond ch2 bond ch2 bond 0 0 O NH ^^zXX^JZ^ NH ch2 N(CH3) N(CH3) ch2 ch2 s s S(O) S(O) ^y^ S(O)2 S(O)2 z^X^X.^ C(O) C(O) C(O)O C(O)O C(O)NH C(O)NH OC(O)O OC(O)O NHC(O)NH NHC(O)NH X L1 Y L2 z -CH2-O-CH2- -CH2-O-CH2- -CH2-O-CH2CH2- -CH2-O-CH2CH2- -(CH2)2-O-(CH2)2- -(CH2)2-O-(CH2)2- -(CH2)3-O-(CH2)2- -(CH2)3-O-(CH2)2- -(CH2)3-O-(CH2)4- -(CH2)3-O-(CH2)4- -CH2C(O)NHCH2- -CH2C(O)NHCH2- -CH2C(O)N(CH3)CH2- -CH2C(O)N(CH3)CH2- -CH2C(O)NHCH(CH3)- -CH2C(O)NHCH(CH3)- -CH2C(O)NH(CH2)2- -CH2C(O)NH(CH2)2- -CH2C(O)NHCH(CH2Ph)- -CH2C(O)NHCH(CH2Ph)- <s

[0740] It would be understood by a person of ordinary skill in the art that any of the biradicals described herein can be bonded to any of biradicals described herein according to the General Formula (A) using any of the two unpaired valence electrons, provided such bond is chemically capable of being formed. Some examples of possible bonding biradicals described herein presented in the Table 2.

[0741] Table 2 Possible bonding of biradicals described herein (non-limiting examples).

[0742] In some embodiments, the compound is of Formula (F): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein all variables are as defined herein.

[0743] In some embodiments, the compound is of Formula (I”): Z I                                                  । L1----Y----L2 (i”) or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein all variables are as defined herein.

[0744] In some embodiments, the compound is of Formula (I-A’): Z L1----Y----L2 (1-A’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein all variables are as defined herein.

[0745] In some embodiments, the compound is of Formula (I-A”): L1----Y----L2 (I-A”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein all variables are as defined herein.

[0746] In some embodiments, the compound is of Formula (I-A-I): L1----Y----L2 (I-A-I), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0747] In some embodiments, the compound is of Formula (I-A-F): L1----Y----L2 (I-A-F), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0748] In some embodiments, the compound is of Formula (I-A-I”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0749] In some embodiments, the compound is of Formula (I-A-I-A): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0750] In some embodiments, the compound is of Formula (I-A-I-A’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0751] In some embodiments, the compound is of Formula (I-A-I-A”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0752] In some embodiments, the compound is of Formula (I-A-I-B): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0753] In some embodiments, the compound is of Formula (I-A-I-B’): (I-A-I-B’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0754] In some embodiments, the compound is of Formula (I-A-I-B”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0755] In some embodiments, the compound is of Formula (I-A-I-B-H): L1----Y----L2 (I-A-I-B-H), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0756] In some embodiments, the compound is of Formula (I-A-I-B-H’): L1----Y----L2 (I-A-I-B-H’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0757] In some embodiments, the compound is of Formula (I-A-I-B-H”): I                 = L1----Y----L2 (I-A-I-B-H”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0758] In some embodiments, the compound is of Formula (I-A-I-C): L1----Y----L2 (I-A-I-C), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0759] In some embodiments, the compound is of Formula (I-A-I-C’): (I-A-I-C’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0760] In some embodiments, the compound is of Formula (I-A-I-C”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0761] In some embodiments, the compound is of Formula (I-A-I-C-H): L1----Y----L2 (I-A-I-C-H), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0762] In some embodiments, the compound is of Formula (I-A-I-C-H’): L1----Y----L2 (I-A-I-C-H’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0763] In some embodiments, the compound is of Formula (I-A-I-C-H”): L1----Y----L2 (I-A-I-C-H”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0764] In some embodiments, the compound is of Formula (I-A-I-D): L1----Y----L2 (I-A-I-D), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0765] In some embodiments, the compound is of Formula (I-A-I-D’): L1----Y----L2 (I-A-I-D’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0766] In some embodiments, the compound is of Formula (I-A-I-D”): I               = L1----Y----L2 (I-A-I-D”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0767] In some embodiments, the compound is of Formula (I-A-I-E): I O I L1----Y----L2 (I-A-I-E), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0768] In some embodiments, the compound is of Formula (I-A-I-E’): L1----Y----L2 (I-A-I-E’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0769] In some embodiments, the compound is of Formula (I-A-I-E”): I                        = 0         = I               = L1----Y----L2 (I-A-I-E”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0770] In some embodiments, the compound is of Formula (I-A-I-F): L1----Y----L2 (I-A-I-F), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0771] In some embodiments, the compound is of Formula (I-A-I-F’): L1----Y----L2 (i-A-l-F’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0772] In some embodiments, the compound is of Formula (I-A-I-F”): I HN        = I                = L1----Y----L2 (la-I-F”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0773] In some embodiments, the compound is of Formula (I-A-I-G): L1----Y----L2 (I-A-I-G), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0774] In some embodiments, the compound is of Formula (I-A-I-G’): L1----Y----L2 (I-A-I-G’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0775] In some embodiments, the compound is of Formula (I-A-I-G”): I                        = o=c       = I                = L1----Y----L2 (I-A-I-G”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0776] In some embodiments, the compound is of Formula (I-A-I-A-a): L1-----------L2 (I-A-I-A-a), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0777] In some embodiments, the compound is of Formula (I-A-I-A-a’): L1-----------L2 (i-A-l-A-a’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0778] In some embodiments, the compound is of Formula (I-A-I-A-a”): L1-----------L2 (I-A-I-A-a”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0779] In some embodiments, the compound is of Formula (I-A-I-A-b): L1----O----L2 (l-A-I-A-b), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0780] In some embodiments, the compound is of Formula (I-A-I-A-b’): L1----O----L2 (i-A-l-A-b’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0781] In some embodiments, the compound is of Formula (I-A-I-A-b”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0782] In some embodiments, the compound is of Formula (I-A-I-A-c): L1----N----L2 I R1            (I-A-I-A-c), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0783] In some embodiments, the compound is of Formula (I-A-I-A-c’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0784] In some embodiments, the compound is of Formula (I-A-I-A-c”): L1----N----L2 l R1            (I-A-I-A-c”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0785] In some embodiments, the compound is of Formula (I-A-I-A-c-H): L1----N----L2 I H            (I-A-I-A-c-H), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0786] In some embodiments, the compound is of Formula (I-A-I-A-c-H’): I H           (I-A-I-A-c-H), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0787] In some embodiments, the compound is of Formula (I-A-I-A-c-H”): L1----N----L2 I H            (i-A-I-A-c-H”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0788] In some embodiments, the compound is of Formula (I-A-I-A-c-M): L1----N----L2 I             (I-A-I-A-c-M), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0789] In some embodiments, the compound is of Formula (I-A-I-A-c-M’): I             (I-A-I-A-c-M’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0790] In some embodiments, the compound is of Formula (I-A-I-A-c-M”): I                  = L1----N----L2 I             (I-A-I-A-c-M”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0791] In some embodiments, the compound is of Formula (I-A-I-A-c-IP): L1----N----L2 or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0792] In some embodiments, the compound is of Formula (I-A-I-A-c-IP’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0793] In some embodiments, the compound is of Formula (I-A-I-A-c-IP”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0794] In some embodiments, the compound is of Formula (I-A-I-A-c-Ar): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0795] In some embodiments, the compound is of Formula (I-A-I-A-c-Ar’): (I-A-I-A-c-Ar’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0796] In some embodiments, the compound is of Formula (I-A-I-A-c-Ar”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof

[0797] In some embodiments, the compound is of Formula (I-A-I-A-d): II O            (I-A-I-A-d), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0798] In some embodiments, the compound is of Formula (I-A-I-A-d’): II O            (i-A-l-A-d’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0799] In some embodiments, the compound is of Formula (I-A-I-A-d”): L1----C----L2 II O            (i-A-l-A-d”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0800] In some embodiments, the compound is of Formula (I-A-I-A-e): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0801] In some embodiments, the compound is of Formula (I-A-I-A-e’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0802] In some embodiments, the compound is of Formula (I-A-I-A-e”): II O              (i-A-l-A-e”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0803] In some embodiments, the compound is of Formula (I-A-I-A-f): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0804] In some embodiments, the compound is of Formula (I-A-I-A-f ): (I-A-I-A-f), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0805] In some embodiments, the compound is of Formula (I-A-I-A-f’): (I-A-I-A-f’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0806] In some embodiments, the compound is of Formula (I-A-I-A-g): II O              (I-A-I-A-g), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0807] In some embodiments, the compound is of Formula (I-A-I-A-g’): (I-A-I-A-g’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0808] In some embodiments, the compound is of Formula (I-A-I-A-g”): I H = L1—C-N—L2 II O              (I-A-I-A-g”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0809] In some embodiments, the compound is of Formula (I-A-I-A-h): II O          (I-A-I-A-h), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0810] In some embodiments, the compound is of Formula (I-A-I-A-h’): (I-A-I-A-h’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0811] In some embodiments, the compound is of Formula (I-A-I-A-h”): I H = L1—N-C—L2 II O          (i-A-l-A-h”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0812] In some embodiments, the compound is of Formula (I-A-I-A-i): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0813] In some embodiments, the compound is of Formula (I-A-I-A-i’): (I-A-I-A-i’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0814] In some embodiments, the compound is of Formula (I-A-I-A-i”): I H H = L1—N-C-N-L2 II O            (i-A-l-A-i”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0815] In some embodiments, the compound is of Formula (I-A-I-A-j): L1-S(O)t—L2 (pa-I-A-j), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein t is 0, 1, or 2 and all other variables are as defined herein.

[0816] In some embodiments, the compound is of Formula (I-A-I-A-i’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein t is 0, 1, or 2 and all other variables are as defined herein.

[0817] In some embodiments, the compound is of Formula (I-A-I-A-i”): L1-S(O)t—?    (i.A-I-A-i”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein t is 0, 1, or 2 and all other variables are as defined herein.

[0818] In some embodiments, the compound is of Formula (I-A-I-A-k): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0819] In some embodiments, the compound is of Formula (I-A-I-A-k’): (I-A-I-A-k’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0820] In some embodiments, the compound is of Formula (I-A-I-A-k”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0821] In some embodiments, the compound is of Formula (I-A-I-B-a): L1-----------L2 (I-A-I-B-a), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0822] In some embodiments, the compound is of Formula (I-A-I-B-a’): L1-----------L2 (I-A-I-B-a’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0823] In some embodiments, the compound is of Formula (I-A-I-B-l-a”): I                 = L1-----------L2 (I-A-I-B-a”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0824] In some embodiments, the compound is of Formula (I-A-I-B-b): L1----O----L2 (I-A-I-B-b) or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0825] In some embodiments, the compound is of Formula (I-A-I-B-b’): L1----O----L2 (I-A-I-B-b’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0826] In some embodiments, the compound is of Formula (I-A-I-B-b”): I                 = L1----O----L2 (I-A-I-B-b”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0827] In some embodiments, the compound is of Formula (I-A-I-B-c): L1----N----L2 l R1           (I-A-I-B-c), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0828] In some embodiments, the compound is of Formula (I-A-I-B-c’): L1----N----L2 I R1           (I-A-I-B-c’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0829] In some embodiments, the compound is of Formula (I-A-I-B-c”): L1----N----L2 l R1            (I-A-I-B-c”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0830] In some embodiments, the compound is of Formula (I-A-I-B-c-H): L1----N----L2 I H            (I-A-I-B-c-H), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0831] In some embodiments, the compound is of Formula (I-A-I-B-c-H’): L1----N----L2 I H            (I-A-I-B-c-H’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0832] In some embodiments, the compound is of Formula (I-A-I-B-c-H”): I                = L1----N----L2 I H            (I-A-I-B-c-H”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0833] In some embodiments, the compound is of Formula (I-A-I-B-c-M): L1----N----L2 I             (I-A-I-B-c-M), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0834] In some embodiments, the compound is of Formula (I-A-I-B-c-M’): I             (I-A-I-B-c-M’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0835] In some embodiments, the compound is of Formula (I-A-I-B-c-M”): I             (I-A-I-B-c-M”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0836] In some embodiments, the compound is of Formula (I-A-I-B-d): II o            (I-A-I-B-d), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0837] In some embodiments, the compound is of Formula (I-A-I-B-d’): L1----C----L2 II O            (I-A-I-B-d’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0838] In some embodiments, the compound is of Formula (I-A-I-B-d”): II O            (I-A-I-B-d”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0839] In some embodiments, the compound is of Formula (I-A-I-B-e): L1—C-O—L2 II O              (I-A-I-B-e), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0840] In some embodiments, the compound is of Formula (I-A-I-B-e’): (I-A-I-B-e’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0841] In some embodiments, the compound is of Formula (I-A-I-B-e”): L1—C-O—L2 II O              (I-A-I-B-e”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0842] In some embodiments, the compound is of Formula (I-A-I-B-f): L1—O-C—L2 II O          (I-A-I-B-f), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0843] In some embodiments, the compound is of Formula (I-A-I-B-f): L1—O-C—L2 II O          (I-A-I-B-l-f), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0844] In some embodiments, the compound is of Formula (I-A-I-B-f’): L1—O-C—L2 II O           (I-A-I-B-f’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0845] In some embodiments, the compound is of Formula (I-A-I-B-g): I H 2 L1—C-N—L2 II O              (I-A-I-B-g), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0846] In some embodiments, the compound is of Formula (I-A-I-B-g’): II O              (I-A-I-B-g’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0847] In some embodiments, the compound is of Formula (I-A-I-B-g”): I H =, L1—C-N—L2 II O              (I-A-I-B-g”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0848] In some embodiments, the compound is of Formula (I-A-I-B-h): I H 2 L1—N-C—L2 II O          (I-A-I-B-h), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0849] In some embodiments, the compound is of Formula (I-A-I-B-h’): II O          (I-A-I-B-h’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0850] In some embodiments, the compound is of Formula (I-A-I-B-l-h”): I H =, L1—N-C—L2 II O          (I-A-I-B-h”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0851] In some embodiments, the compound is of Formula (I-A-I-B-i): II 0            (I-A-I-B-i), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0852] In some embodiments, the compound is of Formula (I-A-I-B-i’): II O            (I-A-I-B-i’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0853] In some embodiments, the compound is of Formula (I-A-I-B-i”): II O            (I-A-I-B-i”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0854] In some embodiments, the compound is of Formula (I-A-I-B-j): L1-S(O)t—L2 (I-A-I-B-j), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein t is 0, 1, or 2 and all other variables are as defined herein.

[0855] In some embodiments, the compound is of Formula (I-A-I-B-i’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein t is 0, 1, or 2 and all other variables are as defined herein.

[0856] In some embodiments, the compound is of Formula (I-A-I-B-i”): L1-S(O)t—L2 or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein t is 0, 1, or 2 and all other variables are as defined herein.

[0857] In some embodiments, the compound is of Formula (I-A-I-B-k): L1 CH2 L2 (I-A-I-B-k), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0858] In some embodiments, the compound is of Formula (I-A-I-B-k’): L1 CH2 L2 (I-A-I-B-k’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0859] In some embodiments, the compound is of Formula (I-A-I-B-k”): L1 CH2 L2 (i-A-I-B-k”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0860] In some embodiments, the compound is of Formula (I-A-I-A-a-1): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0861] In some embodiments, the compound is of Formula (I-A-I-A-a-T) or (I-A-I-A-a-1”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0862] In some embodiments, the compound is of Formula (I-A-I-A-a-2): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0863] In some embodiments, the compound is of Formula (I-A-I-A-a-2’) or (I-A-I-A-a-2”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0864] In some embodiments, the compound is of Formula (l-A-l-A-a-3): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0865] In some embodiments, the compound is of Formula (I-A-I-A-a-3’) or (I-A-I-A-a-3”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0866] In some embodiments, the compound is of Formula (I-A-I-A-a-4): (I-A-I-A-a-4), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0867] In some embodiments, the compound is of Formula (I-A-I-A-a-4’) or (I-A-I-A-a-4”): (I-A-I-A-a-4’), L2 (I-A-I-A-a-4”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0868] In some embodiments, the compound is of Formula (I-A-I-A-a-5): O NH N O H (I-A-I-A-a-5), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0869] In some embodiments, the compound is of Formula (I-A-I-A-a-5’) or (I-A-I-A-a-5”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0870] In some embodiments, the compound is of Formula (I-A-I-A-a-6): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0871] In some embodiments, the compound is of Formula (I-A-I-A-a-6’) or (I-A-I-A-a-6”): L2                                  I              L2 I              (I-A-I-A-a-6),                 I             (I-A-I-A-a-6”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0872] In some embodiments, the compound is of Formula (I-A-I-A-a-7): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0873] In some embodiments, the compound is of Formula (I-A-I-A-a-7’) or (I-A-I-A-a-7”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0874] In some embodiments, the compound is of Formula (l-A-l-A-a-8): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0875] In some embodiments, the compound is of Formula (I-A-I-A-a-8’) or (I-A-I-A-a-8”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0876] In some embodiments, the compound is of Formula (I-A-I-A-a-9): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0877] In some embodiments, the compound is of Formula (I-A-I-A-a-9’) or (I-A-I-A-a-9”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0878] In some embodiments, the compound is of Formula (I-A-I-A-a-10): N (I-A-I-A-a-10), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0879] In some embodiments, the compound is of Formula (I-A-I-A-a-10’) or (I-A-I-A-a-10”): (I-A-I-A-a-10’), (I-A-I-A-a-10”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0880] In some embodiments, the compound is of Formula (I-A-I-A-a-11): N (I-A-I-A-a-11), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0881] In some embodiments, the compound is of Formula (E-I-A-I-A-a-11) or (Z-I-A-I-A-a-11): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0882] In some embodiments, the compound is of Formula (E-I-A-I-A-a-11’), (Z-I-A-I-A-a-11’), (E-I-A-I-A-a-11”), or (Z-I-A-I-A-a-11”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0883] In some embodiments, the compound is of Formula (I-A-I-A-a-12): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0884] In some embodiments, the compound is of Formula (E-I-A-I-A-a-12) or (Z-I-A-I-A-a-12): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0885] In some embodiments, the compound is of Formula (E-I-A-I-A-a-12’), (E-I-A-I-A-a-12”), (Z-I-A-I-A-a-12’), or (Z-I-A-I-A-a-12”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0886] In some embodiments, the compound is of Formula (I-A-I-A-a-13): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0887] In some embodiments, the compound is of Formula (E-I-A-I-A-a-13) or (Z-I-A-I-A-a-13): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0888] In some embodiments, the compound is of Formula (E-I-A-I-A-a-I3’), (E-I-A-I-A-a-13”), (Z-I-A-I-A-a-13’), or (Z-I-A-I-A-a-13”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0889] In some embodiments, the compound is of Formula (I-A-I-A-a-14): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof

[0890] In some embodiments, the compound is of Formula (E-I-A-I-A-a-14) or (Z-I-A-I-A-a-14): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0891] In some embodiments, the compound is of Formula (£-I-A-I-A-a-14’), (E-I-A-I-A-a- M”), (Z-I-A-I-A-a-14’), or (Z-I-A-I-A-a-14”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0892] In some embodiments, the compound is of Formula (I-A-I-A-a-15): (I-A-I-A-a-15), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0893] In some embodiments, the compound is of Formula (E-I-A-I-A-a-15) or (Z-I-A-I-A-a-15): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0894] In some embodiments, the compound is of Formula (E-I-A-I-A-a-15’), (E-I-A-I-A-a-15”), (Z-I-A-I-A-a-15’), or (Z-I-A-I-A-a-15”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0895] In some embodiments, the compound is of Formula (I-A-I-A-a-16): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0896] In some embodiments, the compound is of Formula (E-I-A-I-A-a-16) or (Z-I-A-I-A-a-16): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0897] In some embodiments, the compound is of Formula (E-I-A-I-A-a-16’), (E-I-A-I-A-a-16”), (Z-I-A-I-A-a-16’), or (Z-I-A-I-A-a-16”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0898] In some embodiments, the compound is of Formula (I-A-I-A-a-17): N (I-A-I-A-a-17), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0899] In some embodiments, the compound is of Formula (E-I-A-I-A-a-17) or (E-I-A-I-A-a-17): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0900] In some embodiments, the compound is of Formula (E-I-A-I-A-a-17’), (E-I-A-I-A-a-17”), (Z-I-A-I-A-a-17’), or (Z-I-A-I-A-a-17”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0901] In some embodiments, the compound is of Formula (I-A-I-A-a-18): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0902] In some embodiments, the compound is of Formula (I-A-I-A-a-18’) or (I-A-I-A-a-18”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0903] In some embodiments, the compound is of Formula (I-A-I-A-a-19): (I-A-I-A-a-19), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0904] In some embodiments, the compound is of Formula (I-A-I-A-a-19’) or (I-A-I-A-a-19”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0905] In some embodiments, the compound is of Formula (I-A-I-A-a-20): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0906] In some embodiments, the compound is of Formula (I-A-I-A-a-20’) or (I-A-I-A-a-20”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0907] In some embodiments, the compound is of Formula (I-A-I-A-a-21): N (I-A-I-A-a-21), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0908] In some embodiments, the compound is of Formula (I-A-I-A-a-21’) or (I-A-I-A-a-21”): (I-A-I-A-a-21’), (I-A-I-A-a-21”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0909] In some embodiments, the compound is of Formula (I-A-I-A-a-22): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0910] In some embodiments, the compound is of Formula (I-A-I-A-a-22’) or (I-A-I-A-a-22 ”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0911] In some embodiments, the compound is of Formula (I-A-I-A-a-23): N—N          (I-A-I-A-a-23), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0912] In some embodiments, the compound is of Formula (I-A-I-A-a-23’) or (I-A-I-A-a-23”): N-N          (I-A-I-A-a-23’),           N—N          (I-A-I-A-a-23”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0913] In some embodiments, the compound is of Formula (I-A-I-A-a-24): (I-A-I-A-a-24), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0914] In some embodiments, the compound is of Formula (I-A-I-A-a-24’), (I-A-I-A-a-24”), (I- A-I-A-a-24’”), or (I-A-I-A-a-24””): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0915] In some embodiments, the compound is of Formula (I-A-I-A-a-25): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0916] In some embodiments, the compound is of Formula (I-A-I-A-a-25’), (I-A-I-A-a-25”), (I- A-I-A-a-25’”), or (I-A-I-A-a-25””): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0917] In some embodiments, the compound is of Formula (I-A-I-A-a-26): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0918] In some embodiments, the compound is of Formula (I-A-I-A-a-26’), (I-A-I-A-a-26”), (I- A-I-A-a-26’”), or (I-A-I-A-a-26””): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0919] In some embodiments, the compound is of Formula (I-A-I-A-a-27): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0920] In some embodiments, the compound is of Formula (I-A-I-A-a-27’), (I-A-I-A-a-27”), (I- or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0921] In some embodiments, the compound is of Formula (I-A-I-A-a-28): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0922] In some embodiments, the compound is of Formula (I-A-I-A-a-28’), (I-A-I-A-a-28”), (I- A-I-A-a-28’”), or (I-A-I-A-a-28””): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0923] In some embodiments, the compound is of Formula (I-A-I-A-a-29): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0924] In some embodiments, the compound is of Formula (I-A-I-A-a-29’), (I-A-I-A-a-29”), (I- or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0925] In some embodiments, the compound is of Formula (I-A-I-A-a-30): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0926] In some embodiments, the compound is of Formula (I-A-I-A-a-30’), (I-A-I-A-a-30”), (I- A-I-A-a-30’”), or (I-A-I-A-a-30””): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0927] In some embodiments, the compound is of Formula (I-A-I-A-b-1): CH2 O L2 (I-A-I-A-b-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0928] In some embodiments, the compound is of Formula (I-A-I-A-b-1’) or (I-A-I-A-b-1”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0929] In some embodiments, the compound is of Formula (I-A-I-A-b-2): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0930] In some embodiments, the compound is of Formula (I-A-I-A-b-2’) or (I-A-I-A-b-2”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0931] In some embodiments, the compound is of Formula (I-A-I-A-b-3): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0932] In some embodiments, the compound is of Formula (I-A-I-A-a-3’) or (I-A-I-A-a-3”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0933] In some embodiments, the compound is of Formula (I-A-I-A-b-4): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0934] In some embodiments, the compound is of Formula (I-A-I-A-b-4’) or (I-A-I-A-b-4”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0935] In some embodiments, the compound is of Formula (I-A-I-A-b-5): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0936] In some embodiments, the compound is of Formula (I-A-I-A-b-5’) or (I-A-I-A-b-5”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0937] In some embodiments, the compound is of Formula (I-A-I-A-b-6): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0938] In some embodiments, the compound is of Formula (l-A-l-A-a-6’) or (l-A-l-A-a-6”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0939] In some embodiments, the compound is of Formula (I-A-I-A-b-7): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0940] In some embodiments, the compound is of Formula (I-A-I-A-b-7’) or (I-A-I-A-b-7”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0941] In some embodiments, the compound is of Formula (l-A-l-A-b-8): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0942] In some embodiments, the compound is of Formula (I-A-I-A-b-8’) or (I-A-I-A-b-8”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0943] In some embodiments, the compound is of Formula (I-A-I-A-b-9): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0944] In some embodiments, the compound is of Formula (E-I-A-I-A-b-9) or (Z-I-A-I-A-b-9): or a pharmacally acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0945] In some embodiments, the compound is of Formula (E-I-A-I-A-b-9’), (E-I-A-I-A-b-9”), (Z-I-A-I-A-b-9’), (Z-I-A-I-A-b-9”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0946] In some embodiments, the compound is of Formula (I-A-I-A-b-10): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0947] In some embodiments, the compound is of Formula (E-I-A-I-A-b-10) or (Z-I-A-I-A-b-10): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0948] Tn some embodiments, the compound is of Formula (A-T-A-T-A-b-1 O’), ( / s-T-A-T-A-b-10”), (Z-I-A-I-A-b-10’), or (Z-I-A-I-A-b-10”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0949] In some embodiments, the compound is of Formula (I-A-I-A-b-11): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0950] Tn some embodiments, the compound is of Formula ( / s-T-A-T-A-b-l 1) or (Z-T-A-T-A-b-11): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0951] In some embodiments, the compound is of Formula (I-A-I-A-b-11’), (I-A-I-A-b-11”), (I-A-I-A-b-11’), or (I-A-I-A-b-11”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0952] In some embodiments, the compound is of Formula (I-A-I-A-b-12): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0953] In some embodiments, the compound is of Formula (E-I-A-I-A-b-12) or (Z-I-A-I-A-b-12): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0954] In some embodiments, the compound is of Formula (E-I-A-I-A-b-12’), (E'-I-A-I-A-b-12”), (Z-I-A-I-A-b-12’), (Z-I-A-I-A-b-12”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0955] In some embodiments, the compound is of Formula (I-A-I-A-b-13): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0956] In some embodiments, the compound is of Formula (E-I-A-I-A-b-13) or (Z-I-A-I-A-b-13): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0957] In some embodiments, the compound is of Formula (E-I-A-I-A-b-13’), (E-I-A-I-A-b-13”), (Z-I-A-I-A-b-13’), (Z-I-A-I-A-b-13”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0958] In some embodiments, the compound is of Formula (I-A-I-A-b-14): (I-A-I-A-b-14), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0959] In some embodiments, the compound is of Formula (I-A-I-A-b-14’) or (I-A-I-A-b-14”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0960] In some embodiments, the compound is of Formula (I-A-I-A-b-15): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0961] In some embodiments, the compound is of Formula (I-A-I-A-b-15’) or (I-A-I-A-b-15”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0962] In some embodiments, the compound is of Formula (I-A-I-A-b-16): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0963] In some embodiments, the compound is of Formula (I-A-I-A-b-16’) or (I-A-I-A-b-16”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0964] In some embodiments, the compound is of Formula (I-A-I-A-b-17): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0965] In some embodiments, the compound is of Formula (I-A-I-A-b-17’) or (I-A-I-A-b-17”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0966] In some embodiments, the compound is of Formula (I-A-I-A-b-18): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof

[0967] In some embodiments, the compound is of Formula (I-A-I-A-b-18’) or (I-A-I-A-b-18”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0968] In some embodiments, the compound is of Formula (I-A-I-A-b-19): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0969] In some embodiments, the compound is of Formula (I-A-I-A-b-19’) or (I-A-I-A-b-19”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0970] In some embodiments, the compound is of Formula (I-A-I-A-c-1): CH2—N—L2 H           (I-A-I-A-c-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0971] In some embodiments, the compound is of Formula (I-A-I-A-c-T) or (I-A-I-A-c-1”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0972] In some embodiments, the compound is of Formula (I-A-I-A-c-2): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0973] In some embodiments, the compound is of Formula (I-A-I-A-c-2’) or (I-A-I-A-c-2”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0974] In some embodiments, the compound is of Formula (I-A-I-A-c-3): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0975] In some embodiments, the compound is of Formula (I-A-I-A-c-3’) or (I-A-I-A-c-3”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0976] In some embodiments, the compound is of Formula (I-A-I-A-c-4): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0977] In some embodiments, the compound is of Formula (I-A-I-A-c-4’) or (I-A-I-A-c-4”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0978] In some embodiments, the compound is of Formula (I-A-I-A-c-5): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0979] In some embodiments, the compound is of Formula (I-A-I-A-c-5’) or (I-A-I-A-c-5”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0980] In some embodiments, the compound is of Formula (I-A-I-A-c-6): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0981] In some embodiments, the compound is of Formula (I-A-I-A-c-6’) or (I-A-I-A-c-6”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0982] In some embodiments, the compound is of Formula (I-A-I-A-c-7): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0983] In some embodiments, the compound is of Formula (I-A-I-A-c-7’) or (I-A-I-A-c-7”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0984] In some embodiments, the compound is of Formula (I-A-I-A-d-1): N (I-A-I-A-d-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0985] In some embodiments, the compound is of Formula (I-A-I-A-d-1’) or (I-A-I-A-d-1”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0986] In some embodiments, the compound is of Formula (I-A-I-A-d-2): 0 o (I-A-I-A-d-2), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0987] In some embodiments, the compound is of Formula (I-A-I-A-d-2’) or (I-A-I-A-d-2”): O (I-A-I-A-d-2’),                      O (I-A-I-A-d-2”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0988] In some embodiments, the compound is of Formula (I-A-I-A-d-3): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0989] In some embodiments, the compound is of Formula (I-A-I-A-d-3’) or (I-A-I-A-d-3”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0990] In some embodiments, the compound is of Formula (I-A-I-A-d-4): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0991] In some embodiments, the compound is of Formula (I-A-I-A-d-4’) or (I-A-I-A-d-4”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0992] In some embodiments, the compound is of Formula (I-A-I-A-d-5): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0993] In some embodiments, the compound is of Formula (I-A-I-A-d-5’) or (I-A-I-A-d-5”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0994] In some embodiments, the compound is of Formula (I-A-I-A-e-1): O (I-A-I-A-e-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0995] In some embodiments, the compound is of Formula (I-A-I-A-e-1’) or (I-A-I-A-e-1”): O (I-A-I-A-e-1’),                    O (I-A-I-A-e-1”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0996] In some embodiments, the compound is of Formula (I-A-I-A-e-2): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0997] In some embodiments, the compound is of Formula (I-A-I-A-e-2’) or (I-A-I-A-e-2”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0998] In some embodiments, the compound is of Formula (I-A-I-A-f-1): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[0999] In some embodiments, the compound is of Formula (I-A-I-A-f-T) or (I-A-I-A-f-2”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1000] In some embodiments, the compound is of Formula (I-A-I-A-g-1): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1001] In some embodiments, the compound is of Formula (I-A-I-A-g-1’) or (I-A-I-A-g-1”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1002] In some embodiments, the compound is of Formula (I-A-I-A-g-2): O (l-A-l-A-g-2), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1003] In some embodiments, the compound is of Formula (I-A-I-A-g-2’) or (I-A-I-A-g-2”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1004] In some embodiments, the compound is of Formula (I-A-I-A-h-1): o (I-A-I-A-h-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1005] In some embodiments, the compound is of Formula (I-A-I-A-h-1’) or (I-A-I-A-h-1”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1006] In some embodiments, the compound is of Formula (I-A-I-A-h-2): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1007] In some embodiments, the compound is of Formula (I-A-I-A-h-2’) or (I-A-I-A-h-2”): H (I-A-I-A-h-2’),                    H (I-A-I-A-h-2”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1008] In some embodiments, the compound is of Formula (l-A-l-A-100): (I-A-I-A-100), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1009] In some embodiments, the compound is of Formula (I-A-I-A-101): (I-A-I-A-101), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1010] In some embodiments, the compound is of Formula (I-A-I-A-102): O                   (I-A-I-A-102), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1011] In some embodiments, the compound is of Formula (I-A-I-A-103): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1012] In some embodiments, the compound is of Formula (I-A-I-A-104): (I-A-I-A-104), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1013] In some embodiments, the compound is of Formula (I-A-I-A-105): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1014] In some embodiments, the compound is of Formula (I-A-I-A-106): N- N         (I-A-I-A-106), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1015] In some embodiments, the compound is of Formula (I-A-I-A-107): (I-A-I-A-107), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1016] In some embodiments, the compound is of Formula (I-A-I-A-108): (I-A-I-A-108), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof, wherein i is an integer selected from 0, 1,2, and 3; j is an integer selected from 1, 2, 3, 4 and 5; and all other variables are as defined herein.

[1017] In some embodiments, the compound is of Formula (I-A-I-A-109): (I-A-I-A-109), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1018] In some embodiments, the compound is of Formula (I-A-I-A-110): (I-A-I-A-110), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1019] In some embodiments, the compound is of Formula (I-A-I-A-110'), (I-A-I-A-110”), (I-A-l-A-110’”), or (l-A-l-A-110””): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1020] In some embodiments, the compound is of Formula (I-A-I-A-l 11): (I-A-I-A-lll), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1021] In some embodiments, the compound is of Formula (I-A-I-B-a-1): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1022] In some embodiments, the compound is of Formula (I-A-I-B-a-1’) or (I-A-I-B-a-1”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1023] In some embodiments, the compound is of Formula (I-A-I-B-a-2): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1024] In some embodiments, the compound is of Formula (I-A-I-B-a-2’) or (I-A-I-B-a-2”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1025] In some embodiments, the compound is of Formula (l-A-l-B-a-3): (I-A-I-B-a-3), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1026] In some embodiments, the compound is of Formula (I-A-I-B-a-3’) or (I-A-I-B-a-3”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1027] In some embodiments, the compound is of Formula (I-A-I-B-a-4): (I-A-I-B-a-4), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1028] In some embodiments, the compound is of Formula (I-A-I-B-a-4’) or (I-A-I-B-a-4”): (I-A-I-B-a-4’), L2 (I-A-I-B-a-4”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1029] In some embodiments, the compound is of Formula (I-A-I-B-a-5): O NH N NH H (I-A-I-B-a-5), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1030] In some embodiments, the compound is of Formula (I-A-I-B-a-5’) or (I-A-I-B-a-5”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1031] In some embodiments, the compound is of Formula (I-A-I-B-a-6): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1032] In some embodiments, the compound is of Formula (I-A-I-B-a-6’) or (I-A-I-B-a-6”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1033] In some embodiments, the compound is of Formula (I-A-I-B-a-7): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1034] In some embodiments, the compound is of Formula (I-A-I-B-a-7’) or (I-A-I-B-a-7”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1035] In some embodiments, the compound is of Formula (l-A-l-B-a-8): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1036] In some embodiments, the compound is of Formula (I-A-I-B-a-8’) or (I-A-I-B-a-8”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1037] In some embodiments, the compound is of Formula (I-A-I-B-a-9): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1038] In some embodiments, the compound is of Formula (I-A-I-B-a-9’) or (I-A-I-B-a-9”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1039] In some embodiments, the compound is of Formula (I-A-I-B-a-10): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1040] In some embodiments, the compound is of Formula (I-A-I-B-a-10’) or (I-A-I-B-a-10”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1041] In some embodiments, the compound is of Formula (I-A-I-B-a-11): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1042] In some embodiments, the compound is of Formula (E-I-A-I-B-a-11) or (Z-I-A-I-B-a-11): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1043] In some embodiments, the compound is of Formula (E-I-A-I-B-a-ll’), (Z-I-A-I-B-a-11’), (E-I-A-I-B-a-11”), or (Z-I-A-I-B-a-11”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1044] In some embodiments, the compound is of Formula (I-A-I-B-a-12): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1045] In some embodiments, the compound is of Formula (E-I-A-I-B-a-12) or (Z-I-A-I-B-a-12): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1046] In some embodiments, the compound is of Formula (E-I-A-I-B-a-12’), (E-I-A-I-B-a-12”), (Z-I-A-I-B-a-12’), or (Z-I-A-I-B-a-12”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1047] In some embodiments, the compound is of Formula (I-A-I-B-a-13): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1048] In some embodiments, the compound is of Formula (E-I-A-I-B-a-13) or (Z-I-A-I-B-a-13): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1049] In some embodiments, the compound is of Formula (E-I-A-I-B-a-H’), (E-I-A-I-B-a-13”), (Z-I-A-T-B-a-13’), or (Z-I-A-I-B-a-13”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1050] In some embodiments, the compound is of Formula (I-A-I-B-a-14): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof

[1051] In some embodiments, the compound is of Formula (E-I-A-I-B-a-14) or (Z-I-A-I-B-a-14): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1052] In some embodiments, the compound is of Formula (E-I-A-I-B-a-14’), (E-I-A-I-B-a-14”), (Z-I-A-I-B-a-14’), or (Z-I-A-I-B-a-14”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1053] In some embodiments, the compound is of Formula (I-A-I-B-a-15): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1054] In some embodiments, the compound is of Formula (E-I-A-I-B-a-15) or (Z-I-A-I-B-a-15): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1055] In some embodiments, the compound is of Formula (E-I-A-I-B-a-15’), (E-I-A-I-B-a-15”), (Z-I-A-I-B-a-15’), or (Z-I-A-I-B-a-15”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1056] In some embodiments, the compound is of Formula (I-A-I-B-a-16): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1057] In some embodiments, the compound is of Formula (E-I-A-I-B-a-16) or (Z-I-A-I-B-a-16): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1058] In some embodiments, the compound is of Formula (E-I-A-I-B-a-16’), (E-I-A-I-B-a-16”), (Z-I-A-I-B-a-16’), or (Z-I-A-I-B-a-16”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1059] In some embodiments, the compound is of Formula (I-A-I-B-a-17): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1060] In some embodiments, the compound is of Formula (E-I-A-I-B-a-17) or (E-I-A-I-B-a-17): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1061] In some embodiments, the compound is of Formula (E-I-A-I-B-a-17’), (E-I-A-I-B-a-17”), (Z-I-A-I-B-a-17’), or (Z-I-A-I-B-a-17”): 17”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1062] In some embodiments, the compound is of Formula (I-A-I-B-a-18): or a pharmacally acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1063] In some embodiments, the compound is of Formula (I-A-I-B-a-18’) or (I-A-I-B-a-18”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1064] In some embodiments, the compound is of Formula (I-A-I-B-a-19): (I-A-I-B-a-19), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1065] In some embodiments, the compound is of Formula (I-A-I-B-a-19’) or (I-A-I-B-a-19”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1066] In some embodiments, the compound is of Formula (I-A-I-B-a-20): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1067] In some embodiments, the compound is of Formula (I-A-I-B-a-20’) or (I-A-I-B-a-20”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1068] In some embodiments, the compound is of Formula (I-A-I-B-a-21): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof

[1069] In some embodiments, the compound is of Formula (I-A-I-B-a-21’) or (I-A-I-B-a-21”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1070] In some embodiments, the compound is of Formula (I-A-I-B-a-22): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1071] In some embodiments, the compound is of Formula (I-A-I-B-a-22’) or (I-A-I-B-a-22”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1072] In some embodiments, the compound is of Formula (I-A-I-B-a-23): N—N          (I-A-I-B-a-23), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1073] In some embodiments, the compound is of Formula (I-A-I-B-a-23’) or (I-A-I-B-a-23”): N-N          (I-A-I-B-a-23’),            N—N          (I-A-I-B-a-23”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1074] In some embodiments, the compound is of Formula (I-A-I-B-a-24): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1075] In some embodiments, the compound is of Formula (I-A-I-B-a-24’) or (I-A-I-B-a-24”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1076] In some embodiments, the compound is of Formula (I-A-I-B-b-1): CH2 O L2 (I-A-I-B-b-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1077] In some embodiments, the compound is of Formula (I-A-I-B-b-1’) or (I-A-I-B-b-1”): (I-A-I-B-b-1”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof

[1078] In some embodiments, the compound is of Formula (I-A-I-B-b-2): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1079] In some embodiments, the compound is of Formula (I-A-I-B-b-2’) or (I-A-I-B-b-2”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1080] In some embodiments, the compound is of Formula (I-A-I-B-b-3): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1081] In some embodiments, the compound is of Formula (I-A-I-B-a-3’) or (I-A-I-B-a-3”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1082] In some embodiments, the compound is of Formula (I-A-I-B-b-4): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1083] In some embodiments, the compound is of Formula (I-A-I-B-b-4’) or (I-A-I-B-b-4”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1084] In some embodiments, the compound is of Formula (l-A-l-B-b-5): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1085] In some embodiments, the compound is of Formula (I-A-I-B-b-5’) or (I-A-I-B-b-5”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1086] In some embodiments, the compound is of Formula (I-A-I-B-b-6): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1087] In some embodiments, the compound is of Formula (I-A-I-B-a-6’) or (I-A-I-B-a-6”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1088] In some embodiments, the compound is of Formula (I-A-I-B-b-7): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1089] In some embodiments, the compound is of Formula (I-A-I-B-b-7’) or (I-A-I-B-b-7”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1090] In some embodiments, the compound is of Formula (I-A-I-B-b-8): or a pharmacally acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1091] In some embodiments, the compound is of Formula (I-A-I-B-b-8’) or (I-A-I-B-b-8”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1092] In some embodiments, the compound is of Formula (I-A-I-B-b-9): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1093] In some embodiments, the compound is of Formula (E-I-A-I-B-b-9) or (Z-I-A-I-B-b-9): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1094] In some embodiments, the compound is of Formula (E-I-A-I-B-b-9’), (E-I-A-I-B-b-9”), (Z-I-A-I-B-b-9’), (Z-I-A-I-B-b-9”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1095] In some embodiments, the compound is of Formula (I-A-I-B-b-10): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1096] In some embodiments, the compound is of Formula (E-I-A-I-B-b-10) or (Z-I-A-I-B-b-10): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1097] In some embodiments, the compound is of Formula (E-I-A-I-B-b-10’), (E-I-A-I-B-b-10”), (Z-I-A-I-B-b-10’), or (Z-I-A-I-B-b-10”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof

[1098] In some embodiments, the compound is of Formula (I-A-I-B-b-11): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1099] In some embodiments, the compound is of Formula (E-I-A-I-B-b-11) or (Z-I-A-I-B-b-11): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1100] In some embodiments, the compound is of Formula (I-A-I-B-b-lT), (I-A-I-B-b-11”), (I-A-I-B-b-11’), or (I-A-I-B-b-11”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof. [HOI] In some embodiments, the compound is of Formula (I-A-I-B-b-12): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1102] In some embodiments, the compound is of Formula (E-I-A-I-B-b-12) or (Z-I-A-I-B-b-12): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1103] In some embodiments, the compound is of Formula (E-I-A-I-B-b-12’), (E-I-A-I-B-b-12”), (Z-I-A-I-B-b-12’), (Z-I-A-I-B-b-12”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1104] In some embodiments, the compound is of Formula (I-A-I-B-b-13): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1105] In some embodiments, the compound is of Formula (E-I-A-I-B-b-13) or (Z-I-A-I-B-b-13): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1106] In some embodiments, the compound is of Formula (E-I-A-I-B-b-13’), (E-I-A-I-B-b-13”), (Z-I-A-I-B-b-13’), (Z-I-A-I-B-b-13”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1107] In some embodiments, the compound is of Formula (I-A-I-B-b-14): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1108] In some embodiments, the compound is of Formula (I-A-I-B-b-14’) or (I-A-I-B-b-14”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1109] In some embodiments, the compound is of Formula (I-A-I-B-b-15): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1110] In some embodiments, the compound is of Formula (I-A-I-B-b-15’) or (I-A-I-B-b-15”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1111] In some embodiments, the compound is of Formula (I-A-I-B-b-16): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1112] In some embodiments, the compound is of Formula (I-A-I-B-b-16’) or (I-A-I-B-b-16”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof. [1H3] In some embodiments, the compound is of Formula (I-A-I-B-b-17): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1114] In some embodiments, the compound is of Formula (I-A-I-B-b-17’) or (I-A-I-B-b-17”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof. [1H5] In some embodiments, the compound is of Formula (I-A-I-B-b-18): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof. [1H6] In some embodiments, the compound is of Formula (I-A-I-B-b-18’) or (I-A-I-B-b-18’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof. [1H7] In some embodiments, the compound is of Formula (I-A-I-B-b-19): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1118] In some embodiments, the compound is of Formula (I-A-I-B-b-19’) or (I-A-I-B-b-19”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof [1H9] In some embodiments, the compound is of Formula (I-A-I-B-c-1): I                     2 CH2—N—L2 H            (I-A-I-B-c-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1120] In some embodiments, the compound is of Formula (I-A-I-B-c-1’) or (I-A-I-B-c-1”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof. [H21] In some embodiments, the compound is of Formula (I-A-I-B-c-2): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1122] In some embodiments, the compound is of Formula (I-A-I-B-c-2’) or (I-A-I-B-c-2”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1123] In some embodiments, the compound is of Formula (I-A-I-B-c-3): H (I-A-I-B-c-3), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1124] In some embodiments, the compound is of Formula (I-A-I-B-c-3’) or (I-A-I-B-c-3”): or a pharmacally acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1125] In some embodiments, the compound is of Formula (I-A-I-B-c-4): 1         (I-A-I-B-c-4), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1126] In some embodiments, the compound is of Formula (I-A-I-B-c-4’) or (I-A-I-B-c-4”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1127] In some embodiments, the compound is of Formula (I-A-I-B-c-5): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1128] In some embodiments, the compound is of Formula (I-A-I-B-c-5’) or (I-A-I-B-c-5”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1129] In some embodiments, the compound is of Formula (I-A-I-B-c-6): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1130] In some embodiments, the compound is of Formula (I-A-I-B-c-6’) or (I-A-I-B-c-6”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof. [H31] In some embodiments, the compound is of Formula (I-A-I-B-c-7): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1132] In some embodiments, the compound is of Formula (I-A-I-B-c-7’) or (I-A-I-B-c-7”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1133] In some embodiments, the compound is of Formula (I-A-I-B-d-1): (I-A-I-B-d-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1134] In some embodiments, the compound is of Formula (I-A-I-B-d-T) or (I-A-I-B-d-1”): (I-A-I-B-d-1’), (I-A-I-B-d-1”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1135] In some embodiments, the compound is of Formula (I-A-I-B-d-2): O NH N H NH (I-A-I-B-d-2), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1136] In some embodiments, the compound is of Formula (I-A-I-B-d-2’) or (I-A-I-B-d-2 ”): O (I-A-I-B-d-2’),                      O (I-A-I-B-d-2”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1137] In some embodiments, the compound is of Formula (I-A-I-B-d-3): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1138] In some embodiments, the compound is of Formula (I-A-I-B-d-3’) or (I-A-I-B-d-3”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1139] In some embodiments, the compound is of Formula (I-A-I-B-e-1): NH O (I-A-I-B-e-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1140] In some embodiments, the compound is of Formula (I-A-I-B-e-T) or (I-A-I-B-e-1”): o (I-A-I-B-e-F),                    O (I-A-I-B-e-1”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof. [H41] In some embodiments, the compound is of Formula (I-A-I-B-e-2): (I-A-I-B-e-2), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1142] In some embodiments, the compound is of Formula (I-A-I-B-e-2’) or (I-A-I-B-e-2”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1143] In some embodiments, the compound is of Formula (I-A-I-B-f-1): O (I-A-I-B-f-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1144] In some embodiments, the compound is of Formula (I-A-I-B-f-1’) or (I-A-I-B-f-2”): O (I-A-I-B-f-1’),                     O (I-A-I-B-f-1”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1145] In some embodiments, the compound is of Formula (I-A-I-B-g-1): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1146] In some embodiments, the compound is of Formula (I-A-I-B-g-T) or (I-A-I-B-g-1”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1147] In some embodiments, the compound is of Formula (I-A-I-B-g-2): O (I-A-I-B-g-2), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1148] In some embodiments, the compound is of Formula (I-A-I-B-g-2’) or (I-A-I-B-g-2”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1149] In some embodiments, the compound is of Formula (I-A-I-B-h-1): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1150] In some embodiments, the compound is of Formula (I-A-I-B-h-1’) or (I-A-I-B-h-1”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof. [H51] In some embodiments, the compound is of Formula (I-A-I-B-h-2): H (I-A-I-B-h-2), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1152] In some embodiments, the compound is of Formula (I-A-I-B-h-2’) or (I-A-I-B-h-2”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1153] In some embodiments, the compound is of Formula (I-A-II): ch2 L1----Y----L2 (1-A-1I), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1154] In some embodiments, the compound is of Formula (I-A-II-A): CH2 L1----Y----L2 (I-A-II-A), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1155] In some embodiments, the compound is of Formula (I-A-II-B): CH2 L1----Y----L2 (I-A-II-B), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1156] In some embodiments, the compound is of Formula (A-B): R5 (A-B), or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof, wherein Ra is selected from Ci-Ce alkyl, H, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, =0, NR3R4, CN, NO2, COOR1, CONR3R4; Rb, Rc, Rd are each independently selected from H, halogen, OH, NH2, CN, NO2, Ci-Ce alkyl, and Ci-Ce alkoxy, wherein alkyl or alkoxy is optionally substituted with one or more halogen, CN; X is selected from a bond, O, NR1, C(R2)2, S, S(O), S(O)2, C(O), C(O)O, C(O)NR3, OC(O)O, N(R2)C(O)NR2, arenediyl; R1 is selected from H, Ci-Ce alkyl, C3-C10 cycloalkyl, C2-Cc alkenyl, C2-C6 alkynyl, Ci-Ce acyl, heterocycle, aryl, heteroaryl, and S(O)2R2 wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, Ci-Ce alkyl, Ci-Ce alkoxy, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, heteroaryl; each R2 is independently selected from H, Ci-Ce alkyl, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, and heteroaryl wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, Ci-Ce alkyl, Ci-Ce alkoxy, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, heteroaryl; L1 is selected from C1-C10 alkanediyl, C2-C10 alkenediyl, C2-C10 alkynediyl, C3-C10-cycloalkanediyl, C3-Cio-cycloalkanediyl-Ci-Cio-alkanediyl, arenediyl, arenediyl-Ci-Cw-alkanediyl, heterocyclediyl, heterocyclediyl-Ci-Cw-alkanediyl, heterocyclediyl-C(O), heteroarenediyl, heteroarenediyl-Ci-Cw alkanediyl, Ci-Ce alkanediyl-O-Ci-Cs alkanediyl, Ci-Ce alkanediyl-NR'-Ci-Ce alkanediyl, Ci-Ce alkanediyl-C(O)NR1-Ci-Ce alkanediyl, wherein alkanediyl, alkendiyl, alkynediyl, arenediyl, heterocyclediyl or heteroarenediyl heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Cg alkyl-Ci-Cg alkoxy, Ci-Cg alkyl-NR^Ci-Ce alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2Ci-C6 alkyl; Y is selected from a bond, 0, NR1, C(R2)2, S, S(0), S(0)2, C(0), C(0)0, C(0)NR3, 0C(0)0, N(R2)C(O)NR2; Z is selected from a bond, 0, C(R2)2; Ring A is selected from Cs-Cio-cycloalkane, arene, heterocycle, heteroarene; W is (CH2)w; w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7. 8, 9. and 10; u is an integer selected from 0 and 1; R3 and R4 are each independently selected from H, Ci-Cg alkyl, Ci-Cg acyl and C3-C10 cycloalkyl; or R3 and R4 together with the atoms to which they are attached and any intervening atoms, form a 5-14 membered heterocycle, wherein the heterocycle is optionally substituted with one or more substituents independently selected from halogen, OH, =0, CN, N02, Ci-Ce alkyl, Ci-Cg alkoxy; R5 is selected fromH, halogen, OH, oxo, CN, Ci-Cg alkyl, Ci-Cg alkoxy, Ci-Cg alkyl-Ci-C6 alkoxy, Ci-C6 alkyl-NRkCi-Cg alkyl, NR3R4, -C(O)NR3R4, -S(O)Ci-C6 alkyl, -S(O)2NR3R4, and -S(O)2Ci-C6 alkyl. [H57] In some embodiments, the compound is of Formula (I-A-II-A-a): CH2 L1-----------L2 (I-A-II-A-a), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof

[1158] In some embodiments, the compound is of Formula (I-A-II-A-a-1): (I-A-II-A-a-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1159] In some embodiments, the compound is of Formula (I-A-II-A-h): O (I-A-II-A-h), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1160] In some embodiments, the compound is of Formula (I-A-II-A-h-1): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1161] In some embodiments, the compound is of Formula (I-A-II-A-h-2): O            (I-A-II-A-h-2), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1162] In some embodiments, the compound is of Formula (IF): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein all variables are as defined herein.

[1163] In some embodiments, the compound is of Formula (II”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein all variables are as defined herein.

[1164] In some embodiments, the compound is of Formula (II-A’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein all variables are as defined herein.

[1165] In some embodiments, the compound is of Formula (II-A”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein all variables are as defined herein.

[1166] In some embodiments, the compound is of Formula (II-A-I): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1167] In some embodiments, the compound is of Formula (II-A-F): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1168] In some embodiments, the compound is of Formula (II-A-I”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1169] In some embodiments, the compound is of Formula (II-A-I-A): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1170] In some embodiments, the compound is of Formula (II-A-I-A'): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1171] In some embodiments, the compound is of Formula (II-A-I-A”): or a pharmacally acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1172] In some embodiments, the compound is of Formula (II-A-I-B): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1173] In some embodiments, the compound is of Formula (II-A-I-B’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1174] In some embodiments, the compound is of Formula (II-A-I-B”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1175] In some embodiments, the compound is of Formula (II-A-I-B-H): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1176] In some embodiments, the compound is of Formula (II-A-I-B-H’): NH L2 (II-A-I-B-H’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1177] In some embodiments, the compound is of Formula (II-A-I-B-H”): (II-A-I-B-H”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1178] In some embodiments, the compound is of Formula (II-A-I-C): (II-A-I-C), or a pharmacally acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1179] In some embodiments, the compound is of Formula (II-A-I-C’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1180] In some embodiments, the compound is of Formula (II-A-I-C”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1181] In some embodiments, the compound is of Formula (II-A-I-C-H): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1182] In some embodiments, the compound is of Formula (II-A-I-C-H’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1183] In some embodiments, the compound is of Formula (II-A-I-C-H”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1184] In some embodiments, the compound is of Formula (II-A-I-D): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1185] In some embodiments, the compound is of Formula (II-A-I-D'): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1186] In some embodiments, the compound is of Formula (II-A-I-D”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1187] In some embodiments, the compound is of Formula (II-A-I-E): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1188] In some embodiments, the compound is of Formula (II-A-I-E’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1189] In some embodiments, the compound is of Formula (II-A-I-E”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1190] In some embodiments, the compound is of Formula (II-A-I-F): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof. [H91] In some embodiments, the compound is of Formula (II-A-I-F’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1192] In some embodiments, the compound is of Formula (II-A-I-F”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1193] In some embodiments, the compound is of Formula (II-A-I-G): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1194] In some embodiments, the compound is of Formula (II-A-I-G'): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1195] Tn some embodiments, the compound is of Formula (TT-A-I-G”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1196] In some embodiments, the compound is of Formula (II-A-I-A-a): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1197] In some embodiments, the compound is of Formula (II-A-I-A-a’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1198] In some embodiments, the compound is of Formula (II-A-I-A-a”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1199] In some embodiments, the compound is of Formula (II-A-I-A-b): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1200] In some embodiments, the compound is of Formula (II-A-I-A-b’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1201] In some embodiments, the compound is of Formula (II-A-I-A-b”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1202] In some embodiments, the compound is of Formula (II-A-I-A-c): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1203] In some embodiments, the compound is of Formula (II-A-I-A-c’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1204] Tn some embodiments, the compound is of Formula (TT-A-I-A-c”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1205] In some embodiments, the compound is of Formula (II-A-I-A-c-H): I       / L1--------N H           (II-A-I-A-c-H), or a phamraceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1206] In some embodiments, the compound is of Formula (II-A-I-A-c-H’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1207] In some embodiments, the compound is of Formula (II-A-I-A-c-H”): H           (II-A-I-A-c-H”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1208] In some embodiments, the compound is of Formula (II-A-I-A-c-M): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1209] In some embodiments, the compound is of Formula (II-A-I-A-c-M’): NH L2 (11-A-l-A-c-M), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1210] In some embodiments, the compound is of Formula (II-A-I-A-c-M”): (II-A-I-A-c-M”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof. [12H] In some embodiments, the compound is of Formula (II-A-I-A-d): (II-A-I-A-d), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1212] In some embodiments, the compound is of Formula (II-A-I-A-d’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1213] Tn some embodiments, the compound is of Formula (TI-A-I-A-d”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1214] In some embodiments, the compound is of Formula (II-A-I-A-e): II O                 (II-A-I-A-e), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1215] In some embodiments, the compound is of Formula (II-A-I-A-e’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1216] In some embodiments, the compound is of Formula (II-A-I-A-e”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1217] In some embodiments, the compound is of Formula (II-A-I-A-f): II O            (II-A-I-A-f), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1218] In some embodiments, the compound is of Formula (II-A-I-A-f): II o            (II-A-I-A-f), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1219] In some embodiments, the compound is of Formula (II-A-I-A-f’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1220] In some embodiments, the compound is of Formula (II-A-I-A-g): O                 (II-A-I-A-g), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1221] In some embodiments, the compound is of Formula (II-A-I-A-g’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1222] In some embodiments, the compound is of Formula (II-A-I-A-g”): O                 (II-A-I-A-g”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1223] In some embodiments, the compound is of Formula (II-A-I-A-h): O            (II-A-I-A-h), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1224] In some embodiments, the compound is of Formula (II-A-I-A-h’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1225] In some embodiments, the compound is of Formula (II-A-I-A-h”): O            (II-A-I-A-h”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1226] In some embodiments, the compound is of Formula (II-A-I-A-i): II O             (II-A-I-A-i), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1227] In some embodiments, the compound is of Formula (II-A-I-A-i’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1228] In some embodiments, the compound is of Formula (II-A-I-A-i”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1229] In some embodiments, the compound is of Formula (II-A-I-A-j): L S(O)t (n-A-I-A-j), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein t is 0, 1, or 2 and all other variables are as defined herein.

[1230] In some embodiments, the compound is of Formula (II-A-I-A-i’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein t is 0, 1, or 2 and all other variables are as defined herein.

[1231] In some embodiments, the compound is of Formula (II-A-I-A-i”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein t is 0, 1, or 2 and all other variables are as defined herein.

[1232] In some embodiments, the compound is of Formula (II-A-I-A-k): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1233] In some embodiments, the compound is of Formula (II-A-I-A-k’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1234] In some embodiments, the compound is of Formula (II-A-I-A-k”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1235] In some embodiments, the compound is of Formula (II-A-I-B-a): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1236] In some embodiments, the compound is of Formula (II-A-I-B-a’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1237] In some embodiments, the compound is of Formula (II-A-I-B-a”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1238] In some embodiments, the compound is of Formula (II-A-I-B-b): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1239] In some embodiments, the compound is of Formula (II-A-I-B-b’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1240] In some embodiments, the compound is of Formula (II-A-I-B-b”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1241] In some embodiments, the compound is of Formula (II-A-I-B-c): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1242] In some embodiments, the compound is of Formula (II-A-I-B-c’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1243] Tn some embodiments, the compound is of Formula (TT-A-I-B-c”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1244] In some embodiments, the compound is of Formula (II-A-I-B-c-H): I       / L1--------N H           (II-A-I-B-c-H), or a phamraceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1245] In some embodiments, the compound is of Formula (II-A-I-B-c-H’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1246] In some embodiments, the compound is of Formula (II-A-I-B-c-H”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1247] In some embodiments, the compound is of Formula (II-A-I-B-c-M): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1248] In some embodiments, the compound is of Formula (II-A-I-B-c-M’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1249] In some embodiments, the compound is of Formula (II-A-I-B-c-M”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1250] In some embodiments, the compound is of Formula (II-A-I-B-d): O NH (II-A-I-B-d), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1251] In some embodiments, the compound is of Formula (II-A-I-B-d’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1252] Tn some embodiments, the compound is of Formula (TT-A-I-B-d”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1253] In some embodiments, the compound is of Formula (II-A-I-B-e): II O                  (II-A-I-B-e), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1254] In some embodiments, the compound is of Formula (II-A-I-B-e’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1255] In some embodiments, the compound is of Formula (II-A-I-B-e”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1256] In some embodiments, the compound is of Formula (II-A-I-B-f): II O            (II-A-I-B-f), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1257] In some embodiments, the compound is of Formula (II-A-I-B-f): II o            (II-A-I-B-f), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1258] In some embodiments, the compound is of Formula (II-A-I-B-f’): II O            (II-A-I-B-f’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1259] In some embodiments, the compound is of Formula (II-A-I-B-g): II O                 (II-A-I-B-g), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1260] In some embodiments, the compound is of Formula (II-A-I-B-g’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1261] In some embodiments, the compound is of Formula (II-A-I-B-g”): O                 (II-A-I-B-g”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1262] In some embodiments, the compound is of Formula (II-A-I-B-h): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1263] In some embodiments, the compound is of Formula (II-A-I-B-h’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1264] In some embodiments, the compound is of Formula (II-A-I-B-h”): O            (II-A-I-B-h”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1265] In some embodiments, the compound is of Formula (II-A-I-B-i): II O             (II-A-I-B-i), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1266] In some embodiments, the compound is of Formula (II-A-I-B-i’): (II-A-I-B-i’), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1267] In some embodiments, the compound is of Formula (II-A-I-B-i”): (II-A-I-B-i”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1268] In some embodiments, the compound is of Formula (II-A-I-B-j): (II-A-I-B-j), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein t is 0, 1, or 2 and all other variables are as defined herein.

[1269] In some embodiments, the compound is of Formula (II-A-I-B-i’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein t is 0, 1, or 2 and all other variables are as defined herein.

[1270] In some embodiments, the compound is of Formula (II-A-I-B-i”): L S(O)t (II-A-I-B-i”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof wherein t is 0, 1, or 2 and all other variables are as defined herein.

[1271] In some embodiments, the compound is of Formula (II-A-I-B-k): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1272] In some embodiments, the compound is of Formula (II-A-I-B-k’): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1273] In some embodiments, the compound is of Formula (II-A-I-B-k”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1274] In some embodiments, the compound is of Formula (II-A-I-A-a-1): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1275] In some embodiments, the compound is of Formula (II-A-I-A-a-1’) or (II-A-I-A-a-1”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1276] In some embodiments, the compound is of Formula (II-A-I-A-a-2): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1277] In some embodiments, the compound is of Formula (II-A-I-A-a-2’) or (II-A-I-A-a-2”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1278] In some embodiments, the compound is of Formula (II-A-I-A-a-3): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1279] In some embodiments, the compound is of Formula (l-A-l-A-a-3’) or (l-A-l-A-a-3”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1280] In some embodiments, the compound is of Formula (II-A-I-A-a-4): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1281] In some embodiments, the compound is of Formula (II-A-I-A-a-4’) or (II-A-I-A-a-4”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1282] In some embodiments, the compound is of Formula (II-A-I-A-a-5): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1283] In some embodiments, the compound is of Formula (II-A-I-A-a-5’) or (II-A-I-A-a-5”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1284] In some embodiments, the compound is of Formula (II-A-I-A-a-6): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1285] In some embodiments, the compound is of Formula (II-A-I-A-a-6’) or (II-A-I-A-a-6”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1286] In some embodiments, the compound is of Formula (II-A-I-A-a-7): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1287] In some embodiments, the compound is of Formula (II-A-I-A-a-7’) or (II-A-I-A-a-7”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1288] In some embodiments, the compound is of Formula (II-A-I-A-a-8): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1289] In some embodiments, the compound is of Formula (II-A-I-A-a-8’) or (II-A-I-A-a-8”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1290] In some embodiments, the compound is of Formula (II-A-I-A-a-9): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1291] In some embodiments, the compound is of Formula (II-A-I-A-a-9’) or (II-A-I-A-a-9”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1292] In some embodiments, the compound is of Formula (I-A-I-A-a-10): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1293] In some embodiments, the compound is of Formula (I-A-I-A-a-10’) or (I-A-I-A-a-10”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1294] In some embodiments, the compound is of Formula (II-A-I-A-a-11): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1295] In some embodiments, the compound is of Formula (E-II-A-I-A-a-11) or (Z-II-A-I-A-a-11): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1296] In some embodiments, the compound is of Formula (II-A-I-A-a-12): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1297] In some embodiments, the compound is of Formula (E-II-A-I-A-a-12) or (Z-II-A-I-A-a-12): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1298] In some embodiments, the compound is of Formula (II-A-I-A-a-13): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1299] In some embodiments, the compound is of Formula (E-II-A-I-A-a-IS) or (Z-II-A-I-A-a-13): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1300] In some embodiments, the compound is of Formula (II-A-I-A-a-14): I                  (II-A-I-A-a-14), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1301] In some embodiments, the compound is of Formula (E-II-A-I-A-a-14) or (Z-II-A-I-A-a-14): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1302] In some embodiments, the compound is of Formula (II-A-I-A-a-15): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1303] In some embodiments, the compound is of Formula (E-II-A-I-A-a-15) or (Z-II-A-I-A-a-15): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1304] In some embodiments, the compound is of Formula (II-A-I-A-a-16): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1305] In some embodiments, the compound is of Formula (E-II-A-I-A-a-16) or (Z-II-A-I-A-a-16): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1306] In some embodiments, the compound is of Formula (II-A-I-A-a-17): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1307] In some embodiments, the compound is of Formula (A-ll-A-l-A-a-l 7) or (E-II-A-I-A-a-17): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1308] In some embodiments, the compound is of Formula (II-A-I-A-a-18): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1309] In some embodiments, the compound is of Formula (II-A-I-A-a-18’) or (II-A-I-A-a-18”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1310] In some embodiments, the compound is of Formula (II-A-I-A-a-19): (II-A-I-A-a-19), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1311] In some embodiments, the compound is of Formula (II-A-I-A-a-19’) or (II-A-I-A-a-19”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1312] In some embodiments, the compound is of Formula (II-A-I-A-a-20): N-L2 (II-A-I-A-a-20), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1313] In some embodiments, the compound is of Formula (II-A-I-A-a-20’) or (II-A-I-A-a-20”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1314] In some embodiments, the compound is of Formula (II-A-I-A-a-21): (II-A-I-A-a-21), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof

[1315] In some embodiments, the compound is of Formula (II-A-I-A-a-21’) or (II-A-I-A-a-21”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1316] In some embodiments, the compound is of Formula (II-A-I-A-a-22): (II-A-I-A-a-22), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1317] In some embodiments, the compound is of Formula (II-A-I-A-a-22’) or (II-A-I-A-a-22”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1318] In some embodiments, the compound is of Formula (II-A-I-A-a-23): N—N          (II-A-I-A-a-23), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1319] In some embodiments, the compound is of Formula (II-A-I-A-a-23’) or (II-A-I-A-a-23”): N-N          (II-A-I-A-a-23’),            N-N          (II-A-I-A-a-23”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1320] In some embodiments, the compound is of Formula (II-A-I-A-a-24): (II-A-I-A-a-24), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1321] In some embodiments, the compound is of Formula (II-A-I-A-a-24’), (II-A-I-A-a-24”), (II- A-I-A-a-24’”), or (II-A-I-A-a-24””): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1322] In some embodiments, the compound is of Formula (II-A-I-A-a-25): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1323] In some embodiments, the compound is of Formula (II-A-I-A-a-25’), (II-A-I-A-a-25”), (II- A-I-A-a-25’”), or (II-A-I-A-a-25””): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1324] In some embodiments, the compound is of Formula (II-A-I-A-a-26): (II-A-I-A-a-26) or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1325] In some embodiments, the compound is of Formula (II-A-I-A-a-26’), (II-A-I-A-a-26”), (II- or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1326] In some embodiments, the compound is of Formula (II-A-I-A-a-27): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1327] In some embodiments, the compound is of Formula (II-A-I-A-a-27’), (II-A-I-A-a-27”), (II- A-I-A-a-27’”), or (II-A-I-A-a-27””): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1328] In some embodiments, the compound is of Formula (II-A-I-A-a-28): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1329] In some embodiments, the compound is of Formula (II-A-I-A-a-28’), (II-A-I-A-a-28”), (II- A-I-A-a-28’”), or (II-A-I-A-a-28””): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1330] In some embodiments, the compound is of Formula (II-A-I-A-a-29): (II-A-I-A-a-29), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1331] In some embodiments, the compound is of Formula (II-A-I-A-a-29’), (II-A-I-A-a-29”), (II- A-I-A-a-29’”), or (II-A-I-A-a-29””): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1332] In some embodiments, the compound is of Formula (II-A-I-A-b-1): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1333] In some embodiments, the compound is of Formula (II-A-I-A-b-1’) or (II-A-I-A-b-1”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1334] In some embodiments, the compound is of Formula (II-A-I-A-b-2): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1335] In some embodiments, the compound is of Formula (II-A-I-A-b-2’) or (II-A-I-A-b-2”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1336] In some embodiments, the compound is of Formula (II-A-I-A-b-3): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1337] In some embodiments, the compound is of Formula (II-A-I-A-a-3’) or (II-A-I-A-a-3”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1338] In some embodiments, the compound is of Formula (II-A-I-A-b-4): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1339] In some embodiments, the compound is of Formula (II-A-I-A-b-4’) or (II-A-I-A-b-4”): or a pharmacally acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1340] In some embodiments, the compound is of Formula (II-A-I-A-b-5): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1341] In some embodiments, the compound is of Formula (II-A-I-A-b-5’) or (II-A-I-A-b-5”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1342] In some embodiments, the compound is of Formula (II-A-I-A-b-6): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1343] In some embodiments, the compound is of Formula (ll-A-I-A-a-6’) or (ll-A-l-A-a-6”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1344] In some embodiments, the compound is of Formula (II-A-I-A-b-7): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1345] In some embodiments, the compound is of Formula (II-A-I-A-b-7’) or (II-A-I-A-b-7”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1346] In some embodiments, the compound is of Formula (ll-A-I-A-b-8): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1347] In some embodiments, the compound is of Formula (II-A-I-A-b-8’) or (II-A-I-A-b-8”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof

[1348] In some embodiments, the compound is of Formula (II-A-I-A-b-9): (II-A-I-A-b-9), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1349] In some embodiments, the compound is of Formula (E-I-A-I-A-b-9) or (Z-I-A-I-A-b-9): or a pharmacally acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1350] In some embodiments, the compound is of Formula (II-A-I-A-b-10): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1351] In some embodiments, the compound is of Formula (E-II-A-I-A-b-10) or (Z-II-A-I-A-b- 10): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1352] In some embodiments, the compound is of Formula (II-A-I-A-b-11): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1353] In some embodiments, the compound is of Formula (E-II-A-I-A-b-ll) or (Z-II-A-I-A-b-11): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1354] In some embodiments, the compound is of Formula (II-A-I-A-b-12): (II-A-I-A-b-12), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1355] In some embodiments, the compound is of Formula (E-II-A-I-A-b-12) or (Z-II-A-I-A-b-12): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1356] In some embodiments, the compound is of Formula (II-A-I-A-b-13): (II-A-I-A-b-13), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1357] In some embodiments, the compound is of Formula (E-II-A-I-A-b-13) or (Z-II-A-I-A-b-13): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1358] In some embodiments, the compound is of Formula (II-A-I-A-b-14): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1359] In some embodiments, the compound is of Formula (II-A-I-A-b-14’) or (II-A-I-A-b-14”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1360] In some embodiments, the compound is of Formula (II-A-I-A-b-15): or a pharmacally acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1361] In some embodiments, the compound is of Formula (II-A-I-A-b-15’) or (II-A-I-A-b-15”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1362] In some embodiments, the compound is of Formula (II-A-I-A-b-16): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1363] In some embodiments, the compound is of Formula (II-A-I-A-b-16’) or (II-A-I-A-b-16”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1364] In some embodiments, the compound is of Formula (II-A-I-A-b-17): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1365] In some embodiments, the compound is of Formula (II-A-I-A-b-17’) or (II-A-I-A-b-17”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1366] In some embodiments, the compound is of Formula (II-A-I-A-b-18): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1367] In some embodiments, the compound is of Formula (II-A-I-A-b-18’) or (II-A-I-A-b-18”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1368] In some embodiments, the compound is of Formula (II-A-I-A-b-19): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1369] In some embodiments, the compound is of Formula (II-A-I-A-b-19’) or (II-A-I-A-b-19”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1370] In some embodiments, the compound is of Formula (II-A-I-A-c-1): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1371] In some embodiments, the compound is of Formula (II-A-I-A-c-1’) or (II-A-I-A-c-1”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1372] In some embodiments, the compound is of Formula (II-A-I-A-c-2): H (II-A-I-A-c-2), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1373] In some embodiments, the compound is of Formula (II-A-I-A-c-2’) or (II-A-I-A-c-2”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1374] In some embodiments, the compound is of Formula (ll-A-I-A-c-3): H (II-A-I-A-c-3), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1375] In some embodiments, the compound is of Formula (II-A-I-A-c-3’) or (II-A-I-A-c-3”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1376] In some embodiments, the compound is of Formula (II-A-I-A-c-4): \          (II-A-I-A-c-4), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1377] In some embodiments, the compound is of Formula (II-A-I-A-c-4’) or (II-A-I-A-c-4”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1378] In some embodiments, the compound is of Formula (II-A-I-A-c-5): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1379] In some embodiments, the compound is of Formula (II-A-I-A-c-5’) or (II-A-I-A-c-5”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1380] In some embodiments, the compound is of Formula (II-A-I-A-c-6): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1381] In some embodiments, the compound is of Formula (II-A-I-A-c-6’) or (II-A-I-A-c-6”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1382] In some embodiments, the compound is of Formula (II-A-I-A-c-7): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1383] In some embodiments, the compound is of Formula (II-A-I-A-c-7’) or (II-A-I-A-c-7”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1384] In some embodiments, the compound is of Formula (II-A-I-A-d-1): O (II-A-I-A-d-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1385] In some embodiments, the compound is of Formula (II-A-I-A-d-T) or (II-A-I-A-d-T): O (II-A-I-A-d-T),                   O (II-A-I-A-d-1”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1386] In some embodiments, the compound is of Formula (II-A-I-A-d-2): O (ll-A-l-A-d-2), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1387] In some embodiments, the compound is of Formula (II-A-I-A-d-2’) or (II-A-I-A-d-2”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1388] In some embodiments, the compound is of Formula (II-A-I-A-d-3): (II-A-I-A-d-3), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1389] In some embodiments, the compound is of Formula (II-A-I-A-d-3’) or (II-A-I-A-d-3”): (II-A-I-A-d-3”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1390] In some embodiments, the compound is of Formula (II-A-I-A-d-4): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1391] In some embodiments, the compound is of Formula (II-A-I-A-d-4’) or (II-A-I-A-d-4”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1392] In some embodiments, the compound is of Formula (II-A-I-A-d-5): O (II-A-I-A-d-5), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1393] In some embodiments, the compound is of Formula (II-A-I-A-d-5’) or (II-A-I-A-d-5”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1394] In some embodiments, the compound is of Formula (II-A-I-A-e-1): (II-A-I-A-e-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1395] In some embodiments, the compound is of Formula (II-A-I-A-e-1’) or (II-A-I-A-e-1”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1396] In some embodiments, the compound is of Formula (II-A-I-A-e-2): (II-A-I-A-e-2), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1397] In some embodiments, the compound is of Formula (II-A-I-A-e-2’) or (II-A-I-A-e-2”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1398] In some embodiments, the compound is of Formula (II-A-I-A-f-1): O (II-A-I-A-f-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1399] In some embodiments, the compound is of Formula (II-A-I-A-f-1’) or (II-A-I-A-f-2”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1400] In some embodiments, the compound is of Formula (II-A-I-A-g-1): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1401] In some embodiments, the compound is of Formula (II-A-I-A-g-F) or (II-A-I-A-g-1”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof

[1402] In some embodiments, the compound is of Formula (II-A-I-A-g-2): NH hn^l2 N O H O (II-A-I-A-g-2), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1403] In some embodiments, the compound is of Formula (II-A-I-A-g-2’) or (II-A-I-A-g-2”): NH hn^l2 NH hn^l2 N O H N O H (II-A-I-A-g-2’), (II-A-I-A-g-2”), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1404] In some embodiments, the compound is of Formula (II-A-I-A-h-1): (II-A-I-A-h-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1405] In some embodiments, the compound is of Formula (I-A-I-A-h-1’) or (I-A-I-A-h-1”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1406] In some embodiments, the compound is of Formula (II-A-I-A-h-2): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1407] In some embodiments, the compound is of Formula (II-A-I-A-h-2’) or (II-A-I-A-h-2”): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1408] In some embodiments, the compound is of Formula (II-A-I-A-100): (II-A-I-A-100), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1409] In some embodiments, the compound is of Formula (II-A-I-A-101): (II-A-I-A-101), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1410] In some embodiments, the compound is of Formula (II-A-I-A-102): O                  (II-A-I-A-102), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1411] In some embodiments, the compound is of Formula (II-A-I-A-103): (II-A-I-A-103), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1412] In some embodiments, the compound is of Formula (II-A-I-A-104): O                   (II-A-I-A-104), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1413] In some embodiments, the compound is of Formula (II-A-I-A-105): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1414] In some embodiments, the compound is of Formula (II-A-I-A-106): or a pharmacally acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1415] In some embodiments, the compound is of Formula (II-A-I-A-107): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1416] In some embodiments, the compound is of Formula (II-A-I-A-108): (II-A-I-A-108), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof, wherein i is an integer selected from 0, 1,2, and 3; j is an integer selected from 1, 2, 3, 4 and 5; and all other variables are as defined herein.

[1417] In some embodiments, the compound is of Formula (II-A-I-A-109): (II-A-I-A-109), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1418] In some embodiments, the compound is of Formula (II-A-I-A-110): (II-A-I-A-110), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1419] In some embodiments, the compound is of Formula (II-A-I-A-111): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1420] In some embodiments, the compound is of Formula (II-A-I-B-a-1): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1421] In some embodiments, the compound is of Formula (II-A-I-B-a-2): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1422] In some embodiments, the compound is of Formula (II-A-I-B-a-3): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1423] In some embodiments, the compound is of Formula (II-A-I-B-a-4): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1424] In some embodiments, the compound is of Formula (II-A-I-B-a-5): (II-A-I-B-a-5), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1425] In some embodiments, the compound is of Formula (II-A-I-B-a-6): (II-A-I-B-a-6), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1426] In some embodiments, the compound is of Formula (II-A-I-B-a-7): (II-A-I-B-a-7), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1427] In some embodiments, the compound is of Formula (II-A-I-B-a-8): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1428] In some embodiments, the compound is of Formula (II-A-I-B-a-9): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1429] In some embodiments, the compound is of Formula (II-A-I-B-a-10): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1430] In some embodiments, the compound is of Formula (II-A-I-B-a-11): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1431] In some embodiments, the compound is of Formula (II-A-I-B-a-12): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1432] In some embodiments, the compound is of Formula (II-A-I-B-a-13): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1433] In some embodiments, the compound is of Formula (II-A-I-B-a-14): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1434] In some embodiments, the compound is of Formula (II-A-I-B-a-15): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1435] In some embodiments, the compound is of Formula (II-A-I-B-a-16): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1436] In some embodiments, the compound is of Formula (II-A-I-B-a-17): (II-A-I-B-a-17), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1437] In some embodiments, the compound is of Formula (II-A-I-B-a-18): L2 (II-A-I-B-a-18), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1438] In some embodiments, the compound is of Formula (II-A-I-B-a-19): (II-A-I-B-a-19), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1439] In some embodiments, the compound is of Formula (II-A-I-B-a-20): (II-A-I-B-a-20), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1440] In some embodiments, the compound is of Formula (II-A-I-B-a-21): (II-A-I-B-a-21), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof

[1441] In some embodiments, the compound is of Formula (II-A-I-B-a-22): (II-A-I-B-a-22), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1442] In some embodiments, the compound is of Formula (II-A-I-B-a-23): (II-A-I-B-a-23), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1443] In some embodiments, the compound is of Formula (II-A-I-B-a-24): (II-A-I-B-a-24), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1444] In some embodiments, the compound is of Formula (II-A-I-B-b-1): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1445] In some embodiments, the compound is of Formula (II-A-I-B-b-2): (ll-A-l-B-b-2), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1446] In some embodiments, the compound is of Formula (II-A-I-B-b-3): ZL2 O (II-A-I-B-b-3), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1447] In some embodiments, the compound is of Formula (II-A-I-B-b-4): (II-A-I-B-b-4), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1448] In some embodiments, the compound is of Formula (II-A-I-B-b-5): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1449] In some embodiments, the compound is of Formula (II-A-I-B-b-6): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1450] In some embodiments, the compound is of Formula (II-A-I-B-b-7): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1451] In some embodiments, the compound is of Formula (II-A-I-B-b-8): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1452] In some embodiments, the compound is of Formula (II-A-I-B-b-9): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1453] In some embodiments, the compound is of Formula (II-A-I-B-b-10): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1454] In some embodiments, the compound is of Formula (II-A-I-B-b-11): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1455] In some embodiments, the compound is of Formula (II-A-I-B-b-12): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1456] In some embodiments, the compound is of Formula (II-A-I-B-b-13): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1457] In some embodiments, the compound is of Formula (II-A-I-B-b-14): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1458] In some embodiments, the compound is of Formula (II-A-I-B-b-15): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1459] In some embodiments, the compound is of Formula (II-A-I-B-b-16): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1460] In some embodiments, the compound is of Formula (II-A-I-B-b-17): (II-A-I-B-b-17), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1461] In some embodiments, the compound is of Formula (II-A-I-B-b-18): (II-A-I-B-b-18), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1462] In some embodiments, the compound is of Formula (II-A-I-B-b-19): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1463] In some embodiments, the compound is of Formula (II-A-I-B-c-1): (II-A-I-B-c-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1464] In some embodiments, the compound is of Formula (II-A-I-B-c-2): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1465] In some embodiments, the compound is of Formula (II-A-I-B-c-3): H (II-A-I-B-c-3), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1466] In some embodiments, the compound is of Formula (II-A-I-B-c-4): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1467] In some embodiments, the compound is of Formula (II-A-I-B-c-5): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1468] In some embodiments, the compound is of Formula (II-A-I-B-c-6): (II-A-I-B-c-6), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1469] In some embodiments, the compound is of Formula (II-A-I-B-c-7): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1470] In some embodiments, the compound is of Formula (II-A-I-B-d-1): O (II-A-I-B-d-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1471] In some embodiments, the compound is of Formula (II-A-I-B-d-2): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1472] In some embodiments, the compound is of Formula (II-A-I-B-d-3): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1473] In some embodiments, the compound is of Formula (II-A-I-B-e-1): O (n-A-I-B-e-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1474] In some embodiments, the compound is of Formula (II-A-I-B-e-2): (II-A-I-B-e-2), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1475] In some embodiments, the compound is of Formula (II-A-I-B-f-1): O (II-A-I-B-f-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1476] In some embodiments, the compound is of Formula (II-A-I-B-g-1): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1477] In some embodiments, the compound is of Formula (II-A-I-B-g-2): O (II-A-I-B-g-2), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1478] In some embodiments, the compound is of Formula (II-A-I-B-h-1): or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1479] In some embodiments, the compound is of Formula (II-A-I-B-h-2): H (II-A-I-B-h-2), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotopic derivative, or tautomer thereof.

[1480] In some embodiments, the compound is selected from the compounds described in Table 3 and pharmaceutically acceptable salts, stereoisomers, solvates, prodrugs, isotopic derivatives, or tautomers thereof.

[1481] In some embodiments, the compound is selected from the compounds described in Table 3 and prodrugs and pharmaceutically acceptable salts thereof.

[1482] In some embodiments, the compound is selected from the compounds described in Table 3 and pharmaceutically acceptable salts thereof.

[1483] In some embodiments, the compound is selected from the prodrugs of the compounds described in Table 3 and pharmaceutically acceptable salts thereof.

[1484] In some embodiments, the compound is selected from the compounds described in Table 3.

[1485] Table 3 Certain examples of the compound of Formula A # Structure IUPAC name F ) n HN' / S^\ N 28-[(3-fluoro-2-methoxyphenyl)amino]-3,22- dioxa-6,11,15- z HN -NH 0 triazapentacyclo[21.3.1.110’13.04’9.012’17]octaco sa-l(27),4,6,8,10(28),12,23,25-octaen-14-one / ) F / 0^ 3 0 HN' N vJ (19Z)-28-[(3-fluoro-2-methoxyphenyl)amino] -3,22-dioxa-6,11,15-triazapentacyclo[21.3.1.110’13.04’9.012’17]octaco sa-l(27),4,6,8,10(28),12,19,23,25-nonaen-14- HN -NH 0 one V w o' w F ) HN' 28-[(3-fluoro-2-methoxyphenyl)aminoJ-3,22- O N xJ dioxa-6,11,15- 4 tnazapentacyclo[21.2.2.110’13.04’9.012’17]octaco HN -NH 0 sa-l(25),4,6,8,10(28),12,23,26-octaen-14-one O # Structure IUPAC name F 5 0 HN HN' -NH 0 N J (19Z)-28-[(3-fluoro-2-methoxypheny l)amino] -3,22-dioxa-6,11,15-triazapentacyclo[21.2.2.110’13.04’9.012’17]octaco sa-1 (25),4,6,8,10(28), 12,19,23,26-nonaen-l 4-one V O F 6 (3 HN HNZ -NH °\ N J / 28-[(3-fluoro-2-methoxyphenyl)amino]-8,16-dioxa-5,23,27- triazapentacyclo[23.2.1.02,7.01015.021’26]octaco sa-l(28),2,4,6,10,12,14,25-octaen-24-one ^0' H F \X 7 0 HN HNZ -NH °x N u (18Z)-28-[(3-fluoro-2-methoxyphenyl)amino]-8,16-dioxa-5,23,27-triazapentacyclo[23.2.1.02’7.01015.021’26]octaco sa-1 (28),2,4,6,10,12,14,18,25-nonaen-24-one ^0' J # Structure IUPAC name 18 f 9 i VX  y—J \ H / '----.      0 20-[(3-fluoro-2-methoxyphenyl)amino]-10-methyl-8-oxa-5,15,19-triazatetracyclo[15.2.1.02’7.013’18]icosa- 1 (20),2,4,6,10,17-hexaen-16-one 19 J I I>ijN V^N  V—v \ H / V--     0 20-[(3-fluoro-2-methoxyphenyl)amino]-10-methyl-8-oxa-5,15,19-triazatetracyclo[15.2.1.02’7.013’18]icosa- 1 (20),2,4,6,17 -pentaen-16-one 20 9 HN^Qj hn^\a ^xy-xj* V^N 1 H / L    0 21 - [(3-fluoro-2-methoxyphenyl)amino]-l 1 -methyl-8-oxa-5,16,20- triazatetracyclo[16.2.1.02’7.01419]henicosa-1 (21 ),2,4,6,18-pentaen-17-one 21 9 hnU^J k JCXa / H / (HE)-21-[(3-fluoro-2-methoxy pheny l)amino] -11 -methyl-8-oxa-5,16,20-triazatetracyclo[16.2.1.02’7.01419]henicosa-1 (21 ),2,4,6,11,18-hexaen-17-one # Structure IUPAC name 22 9 T H / °z (HZ)-21-[(3-fluoro-2- methoxy pheny l)amino] -11 -methyl-8-oxa- 5,16,20- triazatetracyclo[16.2.1.02’7.01419]henicosa-1 (21 ),2,4,6,11,18-hexaen-17-one 23 9 / H >0 < 0 (HZ)-22-[(3-fluoro-2- methoxy pheny l)amino] -12-methyl-8-oxa-5,17,21- tri azatetracyclofl 7.2.1.02’7.015,20ldocosa- 1 (22),2,4,6,11,19-hexaen-18-one 24 ^°\7 9 HN iTx V^N III L H A> / 0 (HE)-22-[(3-fluoro-2-methoxy pheny l)amino] -12-methyl-8-oxa-5,17,21-tri azatetracyclofl 7.2.1.02’7.015,20]docosa-1 (22),2,4,6,11,19-hexaen-18-one 25 9 hnX]|\. .. ATj < 0 22-[(3-fluoro-2-methoxyphenyl)amino]-12-methyl-8-oxa-5,17,21-triazatetracyclofl 7.2.1.02,7^15,20]docosa-1 (22),2,4,6,19-pentaen-18-one # Structure IUPAC name 26 J HN-^^ 1 H / (10Z)-21-[(3-fluoro-2- methoxy pheny l)amino] -11 -methyl-8-oxa- 5,16,20- triazatetracyclo[16.2.1.02’7.01419]henicosa- 1 (21 ),2,4,6,10,18-hexaen-17-one 27 GO ^J) (10E)-21-[(3-fluoro-2- methoxy pheny l)aminol -11 -methyl-8-oxa- 5,16,20- triazatetracyclo[16.2.1.02’7.01419]henicosa- 1 (21 ),2,4,6,10,18-hexaen-17-one 28 j? r GO > 0 (HZ)-22-[(3-fluoro-2- methoxyphenyl)amino] -11,12-dimethyl-8-oxa-5,17,21 -tri azatetracyclofl 7.2.1.0^.015 20]docosa-1 (22),2,4,6,11,19-hexaen-18-one 29 I y-Z GO O--        )--( IZ           i / G   y   \ \ K^°\ J. " o cz z— (19A)-28-[(3-fluoro-2- methoxyphenyl)amino] -3,22-dioxa-6,11,15-triazapentacyclo[21.3.1.110’13.04’9.012’17]octaco sa-l(27),4,6,8,10(28),12,19,23,25-nonaen-14-one IUPAC name (19E)-28-[(3-fluoro-2- methoxyphenyl)amino] -3,22-dioxa-6,11,15-triazapentacyclo[21.2.2.110’13.04’9.012’17]octaco sa-1 (25),4,6,8,10(28), 12,19,23,26-nonaen-l 4- one (18E)-28-[(3-fluoro-2-methoxyphenyl)amino]-8,16-dioxa-5,23,27-triazapentacyclo[23.2.1.02’7.010’15.021’26]octaco sa-1 (28),2,4,6,10,12,14,18,25-nonaen-24-one (HE)-22-[(3-fluoro-2-methoxyphenyl)amino] -11,12-dimethyl-8-oxa-5,17,21 -triazatetracyclo[17.2.1.02’7.015,20]docosa-1 (22),2,4,6,11,19-hexaen-18-one # Structure IUPAC name F 36 HN' 0 HN^k^ i % 24-[(3-fluoro-2-methoxyphenyl)amino]-14-methyl-8,11 -dioxa-5,19,23 -tri azatetr acyclof 19.2.1.027.017’22]tetracosa-1 (24),2,4,6,21 -pentaen-20-one cj —0 F 37 HN' 0 hn A. H / "■" HNZ ) -N 20-[(3-fluoro-2-methoxyphenyl)amino]-5,8,15,19- tetraazatetracyclo[15.2.1.02<01318]icosa-1 (20),2,4,6,17-pentaen-10-yn-16-one 38 HN' 0 ^°\ HN^x "^N^ S— H 0 F ) / N 22-[(3-fluoro-2-methoxyphenyl)amino]-8-oxa-5,17,21-triazatetracyclo(l 7.2.1.02’7.015,2°Jdocosa-1 (22),2,4,6,19-pentaen-18-one 39 HN' 0 —0 hn^A^ ^N^ S— H / ° F N 23-[(3-fluoro-2-methoxyphenyl)amino]-8-oxa-5,18,22- tri azatetracyclofl 8.2.1.02’7.016,21]tricosa- 1 (23),2,4,6,20-pentaen-19-one # Structure IUPAC name 40 F rv°\ 9 NH l IHj V^N V— I H 1 \      0 o-O N 25-[(3-fluoro-2-methoxyphenyl)amino]-8-oxa-5,13,14,15,20,24- hexaazapentacyclo|20.2.1.113,16.02,7.018,23 J -hexacosa-1 (25),2,4,6,14,16(26),22-heptaen-21-one 41 F ry°\ 9 NH hn^><A / ==\ L I W / J H 1 \ °\ Z N—< / N 24-[(3-fluoro-2-methoxyphenyl)amino]-8-oxa-5,12,13,14,19,23- hexaazapentacyclo[19.2.1.112,15.02,7.017,22] -pentacos a-1 (24),2,4,6,13,15 (25),21 -heptaen-20-one 42 F O-o 9    NH hnXZ|T\^ / ^\ \ H / ° 0=<f J N 25 - [(3 -fluoro-2-methoxy pheny l)amino] -18-oxa-1,6,10,15- tetraazapentacyclo[18.3.1.1811.04’9.01217]-pentacosa-8,11 (25), 12,14,16-pentaene-2,7 -dione # Structure IUPAC name 43 F (w 9 NH T H ui 28- [(3-fluoro-2-methoxy phenyl)amino] -3,21 -dioxa-6,11,15,23- tetraazapentacy cl o[21.3.1.11013.04’9.01217]-octacosa-4,6,8,10(28), 12-pentaene-14,22-dione 44 F Qv 9 NH U^nL / | H J 0 yt / 0 '— 27 - [(3-fluoro-2-methoxy phenyl)amino] -3,20-dioxa-6,11,15,22-tetra...

Claims

1. A compound of Formula (A):L1----Y----L2 (A),or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof, whereinRa is C1-C6 alkyl;Rb, Rc, Rd are each independently selected from H, halogen, OH, NH2, CN, NO2, C1-C6 alkyl, and C1-C6 alkoxy, wherein alkyl or alkoxy is optionally substituted with one or more halogen, CN;X is selected from O and NR1;R1 is H;each R2 is independently selected from H, C1-C6 alkyl, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, and heteroaryl wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, C1-C6 alkyl, C1-C6 alkoxy, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, heteroaryl;Y is selected from a bond, O, NR1, C(R2)2, S, S(O), S(O)2, C(O), C(O)O, C(O)NR1, OC(O)O, N(R2)C(O)NR2;Z is selected from a bond, O, C(R2)2;L1 is selected from heterocyclediyl-C1-C10-alkanediyl, C1-C10 alkanediyl, C2-C10 alkenediyl, C2-C10 alkynediyl, C3-C10-cycloalkanediyl, C3-C10-cycloalkanediyl-C1-C10-alkanediyl, arenediyl, arenediyl-C1-C10-alkanediyl, heterocyclediyl, heterocyclediyl-C(O), heteroarenediyl, heteroarenediyl-C1-C10 alkanediyl, CrC6 alkanediyl-O-C1-C6 alkanediyl, CrC6 alkanediyl-NR1-C1-C6 alkanediyl, CrC6 alkanediyl-C(O)NR1-C1-C6 alkanediyl, wherein each alkanediyl, alkenediyl, alkynediyl, arenediyl, heterocyclediyl or heteroarenediyl is optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN,2023257355   28 May 2026C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl-C1-C6 alkoxy, C1-C6 alkyl-NR1-C1-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)C1-C6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2CrC6 alkyl;L2 is selected from C1-C10 alkanediyl, C2-C10 alkenediyl, C2-C10 alkynediyl, C3-C10-cycloalkanediyl,          C3-C10-cycloalkanediyl-C1-C10-alkanediyl,          arenediyl,arenediyl-C1-C10-alkanediyl,         heterocyclediyl,         heterocyclediyl-C1-C10-alkanediyl,heterocyclediyl-C(O), heteroarenediyl,     heteroarenediyl-C1-C10    alkanediyl,    C1-C6alkanediyl-O-C1-C6 alkanediyl, C1-C6 alkanediyl-NR1-C1-C6 alkanediyl, C1-C6 alkanediyl-C(O)NR1-C1-C6 alkanediyl, wherein each alkanediyl, alkendiyl, alkynediyl, arenediyl, heterocyclediyl or heteroarenediyl is optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl-C1-C6 alkoxy, C1-C6 alkyl-NR1-C1-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)C1-C6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2C1-C6 alkyl;provided that at least one from L1 and L2 is selected from optionally substituted heterocyclediyl-C1-C10-alkanediyl, C3-C10-cycloalkanediyl, C3-C10-cycloalkanediyl-C1-C10-alkanediyl, arenediyl, arenediyl-C1-C10-alkanediyl, heterocyclediyl, heterocyclediyl-C(O), heteroarenediyl, heteroarenediyl-C1-C10 alkanediyl;R3 and R4 are each independently selected from H, C1-C6 alkyl, C1-C6 acyl and C3-C10 cycloalkyl;or R3 and R4, together with the atoms to which they are attached and any intervening atoms, form a 5-14 membered heterocycle, wherein the heterocycle is optionally substituted with one or more substituents independently selected from halogen, OH, =O, CN, NO2, C1-C6 alkyl, C1-C6 alkoxy;wherein,aryl is cyclic, aromatic hydrocarbon groups that have 1 to 3 aromatic rings;arenediyl is an organic radical derived from an aromatic divalent radical by removal of two hydrogens;heterocyclyl is saturated or partially unsaturated 3-10 membered monocyclic, 7-12 membered bicyclic (fused, bridged, or spiro rings), or 11-14 membered tricyclic ring system (fused, bridged, or spiro rings) having one or more heteroatoms selected from O, N, S, P, Se, or B;heterocyclediyl is a divalent functional group derived from heterocycle by the removal of two hydrogen atoms from ring atoms;2023257355   28 May 2026heteroaryl is a monovalent monocyclic or a polycyclic aromatic radical of 5 to 24 ring atoms, containing one or more ring heteroatoms selected from N, O, S, P, or B, the remaining ring atoms being C;heteroarenediyl is a divalent functional group derived from heteroarenes by the removal of two hydrogen atoms from ring atoms.

2. A compound of claim 1, wherein the compound is of Formula (I):(I),or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof.

3. A compound of claim 2, wherein the compound is of Formula (I’) or Formula (I”):(I’),or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof.

4. A compound of claim 1, wherein the compound is of Formula (II):2023257355   28 May 2026A compound of claim 4, wherein the compound is of Formula (II’) or Formula (II”):5.(II),or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof.(II’), or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof.(II”),6. A compound of anyone of claims 1-5, or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof, whereinRa is selected from H, C1-C6 alkyl, C2-C6 alkenyl, wherein the alkyl or alkenyl is optionally substituted with one or more substituents independently selected from halogen, OH, =O, NH2, CN, NO2;Rb, Rc, Rd are each independently selected from H, halogen, OH, NH2, CN, NO2, C1-C6 alkyl, C1-C6 alkoxy;X is selected from a bond, -O-, -NH-, -N(CH3)-, -CH2-, -S-, -S(O)-, -S(O)2-, -C(O)-, -C(O)O-, -C(O)NH-, -OC(O)O-, -NHC(O)NH-;2023257355   28 May 2026I o=s=oJ\.NH2Y is selected from a bond, -O-, -NH-, -N(CH3)-, -N(CH(CH3)2)-,                , -CH2-,-S-, -S(O)-, -S(O)2-, -C(O)-, -C(O)O-, -C(O)NH-, -OC(O)O-, -NHC(O)NH-;Z is selected from a bond, -O-, -CH2-;L1 is selected from -CH2-, -(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -CH2CH(CH3)CH2-, -CH(CH3)(CH2)2-, -CH2CH(CH3)(CH2)2-, -(CH2)2CH(CH3)(CH2)-, -CH2CH(CH3)CH(CH3)(CH2)2-, -(CH2)2CH(CH3)(CH2)3-, -(CH2)2CH(CH3)CH(CH3)(CH2)2-, -CH2-O-CH2-,     -CH2-O-(CH2)2-, -(CH2)2-O-(CH2)2-, -CH=CH-, -CH2-CH=CH-,-CH2-C(CH3)=CH-,   -CH2-CH=C(CH3)-,   -CH2-CH=CH-CH2-,   -CH2-C(CH3)=CH-CH2-,-(CH2)2C(CH3)=CH-, -(CH2)2CH=CHCH2-, -(CH2)2C(CH3)=CHCH2-, -(CH2)2CH=C(CH3)CH2-,-(CH2)2C(CH3)=C(CH3)CH2-,   -(CH2)2C(CH3)=CH(CH2)2-,   -(CH2)2C(CH3)=C(CH3)(CH2)2-,-CH2-C(O)NH-CH(CH3)-, -CH2-C(O)NH-CH2CH2-,577N=N      N—N2023257355   28 May 20262023257355   28 May 2026wherein L1 and L2 are optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, NH2.

7. A compound of claim 1, wherein the compound is of Formula (A-I):L1----Y----L2 (A-1), or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof.

8. A compound of claim 7, wherein the compound is of Formula (A-1-a):L1----Y----L2 (A-1-a), or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof.

9. A compound of claim 7, wherein the compound is of Formula (A-1-b):or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof.

10. A compound of claim 2, wherein the compound is of Formula (I-A):2023257355   28 May 2026or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof.

11. A compound of claim 10, wherein the compound is of Formula (I-A-I):or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof.

12. A compound of claim 11, wherein the compound is of Formula:2023257355   28 May 2026(I-A-I-A-c),(I-A-I-A-e),(I-A-I-A-g),(I-A-I-A-d),(I-A-I-A-f),(I-A-I-A-h),(I-A-I-A-i),(I-A-I-B-d),(I-A-I-A-j),(I-A-I-B-a),(I-A-I-B-c),2023257355   28 May 2026(I-A-I-A-k),(I-A-I-B-b),(I-A-I-B-e),2023257355   28 May 2026or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof, wherein t is an integer selected from 0, 1, and 2 and all other variables are as defined herein.

13. A compound of claim 4, wherein the compound is of Formula (II-A):2023257355   28 May 2026or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof.

14. A compound of claim 13, wherein the compound is of Formula (II-A-I):or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof.

15. A compound of claim 14, wherein the compound is of Formula:2023257355   28 May 2026(II-A-I-A-d),(II-A-I-A-c),(II-A-I-A-e),(II-A-I-A-f),(II-A-I-A-g),(II-A-I-A-h),(II-A-I-A-j),(II-A-I-A-i),2023257355   28 May 2026(II-A-I-A-k),(II-A-I-B-a),(II-A-I-B-b),(II-A-I-B-c),O           (II-A-I-B-d),(II-A-I-B-e),IIO             (II-A-I-B-f),(II-A-I-B-g),2023257355   28 May 2026or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof, wherein t is aninteger selected from 0, 1, and 2 and all other variables are as defined herein.

16. A compound of Formula (A-A):(A-A), or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof, whereinRa is selected from C1-C6 alkyl, H, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, =O, NR3R4, CN, NO2, COOR1, CONR3R4;2023257355   28 May 2026Rb, Rc, Rd are each independently selected from H, halogen, OH, NH2, CN, NO2, C1-C6 alkyl, and C1-C6 alkoxy, wherein alkyl or alkoxy is optionally substituted with one or more halogen, CN;X is selected from a bond, O, NR1, C(R2)2, S, S(O), S(O)2, C(O), C(O)O, C(O)NR1, OC(O)O, N(R2)C(O)NR2, arenediyl;R1 is selected from H, C1-C6 alkyl, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 acyl, heterocycle, aryl, heteroaryl, and S(O)2R2 wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, C1-C6 alkyl, C1-C6 alkoxy, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, heteroaryl;each R2 is independently selected from H, C1-C6 alkyl, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, and heteroaryl wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, C1-C6 alkyl, C1-C6 alkoxy, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, heteroaryl;Y is selected from a bond, O, NR1, C(R2)2, S, S(O), S(O)2, C(O), C(O)O, C(O)NR1, OC(O)O, N(R2)C(O)NR2;Z is selected from a bond, O, C(R2)2;Ring A is selected from C3-C10-cycloalkane, arene, heterocycle, heteroarene;W is (CH2)w;w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;L2 is selected from C1-C10 alkanediyl, C2-C10 alkenediyl, C2-C10 alkynediyl, C3-C10-cycloalkanediyl,          C3-C10-cycloalkanediyl-C1-C10-alkanediyl,          arenediyl,arenediyl-C1-C10-alkanediyl,         heterocyclediyl,         heterocyclediyl-C1-C10-alkanediyl,heterocyclediyl-C(O), heteroarenediyl,     heteroarenediyl-C1-C10    alkanediyl,    C1-C6alkanediyl-O-C1-C6 alkanediyl, C1-C6 alkanediyl-NR1-C1-C6 alkanediyl,    C1-C6alkanediyl-C(O)NR1-C1-C6 alkanediyl, wherein each alkanediyl, alkendiyl, alkynediyl, arenediyl, heterocyclediyl or heteroarenediyl is optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl-C1-C6 alkoxy, C1-C6 alkyl-NR1-C1-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)C1-C6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2C1-C6 alkyl;R3 and R4 are each independently selected from H, C1-C6 alkyl, C1-C6 acyl and C3-C10 cycloalkyl;2023257355   28 May 2026or R3 and R4, together with the atoms to which they are attached and any intervening atoms, form a 5-14 membered heterocycle, wherein the heterocycle is optionally substituted with one or more substituents independently selected from halogen, OH, =O, CN, NO2, C1-C6 alkyl, C1-C6 alkoxy;R5 is selected from H, halogen, OH, oxo, CN, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl-C1-C6 alkoxy, C1-C6 alkyl-NR1-C1-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)C1-C6 alkyl, -S(O)2NR3R4, and -S(O)2C1-C6 alkyl.

17. A compound of Formula (A-B):R5 (A-B), or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof, whereinRa is selected from C1-C6 alkyl, H, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, =O, NR3R4, CN, NO2, COOR1, CONR3R4;Rb, Rc, Rd are each independently selected from H, halogen, OH, NH2, CN, NO2, C1-C6 alkyl, and C1-C6 alkoxy, wherein alkyl or alkoxy is optionally substituted with one or more halogen, CN;X is selected from a bond, O, NR1, C(R2)2, S, S(O), S(O)2, C(O), C(O)O, C(O)NR1, OC(O)O, N(R2)C(O)NR2, arenediyl;R1 is selected from H, CrC6 alkyl, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 acyl, heterocycle, aryl, heteroaryl, and S(O)2R2 wherein the alkyl, alkenyl, alkynyl, heterocycle, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, CrC6 alkyl, CrC6 alkoxy, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, heteroaryl;each R2 is independently selected from H, C1-C6 alkyl, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, and heteroaryl wherein the alkyl, alkenyl, alkynyl, heterocycle, 5882023257355   28 May 2026cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, OH, NH2, CN, C1-C6 alkyl, C1-C6 alkoxy, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocycle, aryl, heteroaryl;L1 is selected from C1-C10 alkanediyl, C2-C10 alkenediyl, C2-C10 alkynediyl, C3-C10-cycloalkanediyl,          C3-C10-cycloalkanediyl-C1-C10-alkanediyl,          arenediyl,arenediyl-C1-C10-alkanediyl,         heterocyclediyl,         heterocyclediyl-C1-C10-alkanediyl,heterocyclediyl-C(O), heteroarenediyl,     heteroarenediyl-C1-C10 alkanediyl,    C1-C6alkanediyl-O-C1-C6    alkanediyl,    C1-C6 alkanediyl-NR1-C1-C6 alkanediyl, C1-C6alkanediyl-C(O)NR1-C1-C6 alkanediyl, wherein each alkanediyl, alkendiyl, alkynediyl, arenediyl, heterocyclediyl or heteroarenediyl is optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CN, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl-C1-C6 alkoxy, C1-C6 alkyl-NR1-C1-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)CrC6 alkyl, -S(O)2NR3R4, aryl, and -S(O)2CrC6 alkyl;Y is selected from a bond, O, NR1, C(R2)2, S, S(O), S(O)2, C(O), C(O)O, C(O)NR1, OC(O)O, N(R2)C(O)NR2;Z is selected from a bond, O, C(R2)2;Ring A is selected from C3-C10-cycloalkane, arene, heterocycle, heteroarene;W is (CH2)w;w is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;u is an integer selected from 0 and 1;R3 and R4 are each independently selected from H, C1-C6 alkyl, C1-C6 acyl and C3-C10 cycloalkyl;or R3 and R4, together with the atoms to which they are attached and any intervening atoms, form a 5-14 membered heterocycle, wherein the heterocycle is optionally substituted with one or more substituents independently selected from halogen, OH, =O, CN, NO2, C1-C6 alkyl, C1-C6 alkoxy;R5 is selected from H, halogen, OH, oxo, CN, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl-Cj-C6 alkoxy, C1-C6 alkyl-NR1-C1-C6 alkyl, NR3R4, -C(O)NR3R4, -S(O)CrC6 alkyl, -S(O)2NR3R4, and -S(O)2CrC6 alkyl.

18. A compound selected from:2023257355   28 May 2026# Structure IUPAC name 2 F HN 0 k. J wVV h / Vnh o / A / O 28-[(3 -fluoro-2-methoxyphenyl)amino] -3,22-di oxa-6,11,15-triazapentacyclo[21.3.1.110,13.04,9.012 ,17]-octacosa-1 (27),4,6,8,10(28), 12,23,25-octaen -14-one 3 F HN    ^=\ 0 k J „N WtV HN VNH J so (19 Z)-2 8-[(3 -fluoro-2-methoxyphenyl)amino] -3, 22-dioxa-6,11,15-triazapentacyclo[21.3.1.110,13.0 4,9.012,17]-octacosa-1(27),4,6,8,10(28),12,19,23,2 5-nonaen-14-one 4 F HN HN^ V-NH 28-[(3 -fluoro-2-methoxyphenyl)amino] -3,22-di oxa-6,11,15-triazapentacyclo[21.2.2.110,13.04,9.012 ,17]-octacosa-1 (25),4,6,8,10(28), 12,23,26-octaen -14-one2023257355   28 May 2026# Structure IUPAC name F CK 5 cy HN HN -NH N 0 (19 Z-28-[(3-fluoro-2-methoxyphenyl)amino]-3, 22-dioxa-6,11,15-triazapentacyclo[21.2.2.110,13.0 4,9.012,17]-octacosa-1(25),4,6,8,10(28),12,19,23,2 6-nonaen-14-one V O F z0^ f' 6 0 HNZ N II 28-[(3-fluoro-2-methoxyphenyl)amino]-8,16-di oxa-5,23,27-triazapentacyclo[23.2.1.02,7.010,15.021 ,26]-octacosa-1 (28),2,4,6,10,12,14,25-octaen-24- HN -NH °\ one ^oz u F z0^ f' 7 HNZ N J! (18Z)-28-[(3-fluoro-2-methoxyphenyl)amino]-8 ,16-dioxa-5,23,27-triazapentacyclo[23.2.1.02,7.01 0,15.021,26]-octacosa-1 (28),2,4,6,10,12,14,18,25-n HN -NH °\ onaen-24-one ^0' u2023257355   28 May 2026# Structure IUPAC name 11 0 HN- / ZNH । ( H           1 X     A. /       0 ^N— 25-[(3-fluoro-2-methoxyphenyl)amino]-18-oxa-1,6,10,15 -tetraazapentacyclo [18.3.1.18,11.04,9.012,1 7]-pentacosa-8,11 (25), 12,14,16-pentaen-7-one 12 LI o hm- / nh । V<x \ H / L^N /   o 26-[(3-fluoro-2-methoxyphenyl)amino]-3-oxa-6 ,11,15,21 -tetraazapentacyclo [19.3.1.110,13.04,9.012, 17]-hexacosa-4,6,8,10(26),12-pentaen-14-one 14 o II / A / \z z / z         \ \ )    K / ° V_Z    iz | y^z^x / = / □: \ / i_Z -° 26-[(3-fluoro-2-methoxyphenyl)amino]-3-oxa-6 ,11,15,21 -tetraazapentacyclo [19.3.1.110,13.04,9.012, 17]-hexacosa-4,6,8,10(26), 12-pentaene-14,20-di one2023257355   28 May 2026# Structure IUPAC name 29 ' T ZT o= / z— / □Z (19 E)-28-[(3-fluoro-2-methoxyphenyl)amino]-3 ,22-dioxa-6,11,15-triazapentacyclo[21.3.1.110,13. 04,9.012,17]-octacosa-1(27),4,6,8,10(28),12,19,23, 25-nonaen-14-one 30 F HN 0 Jx--\ / / N hi / y^NH 0 (19 E)-28-[(3-fluoro-2-methoxyphenyl)amino]-3 ,22-dioxa-6,11,15-triazapentacyclo[21.2.2.110,13. 04,9.012,17]-octacosa-1(25),4,6,8,10(28),12,19,23, 26-nonaen-14-one 31 F xb HN 0, L / n HjV HN VNH lly° v3 (18 E)-28-[(3-fluoro-2-methoxyphenyl)amino]-8 , 16-dioxa-5,23,27-triazapentacyclo[23.2.1.02,7.01 0,15.021,26]-octacosa-1 (28),2,4,6,10,12,14,18,25-n onaen-24-one2023257355   28 May 2026# Structure IUPAC name 40 F Fy°\ 9 NH AW / H 1 \ °\ tON^J in-N 25-[(3-fluoro-2-methoxyphenyl)amino]-8-oxa-5 ,13,14,15,20,24-hexaazapentacyclo[20.2.1.113,16. 02,7.018,23]-hexacosa-1 (25),2,4,6,14,16(26),22-he ptaen-21-one 41 I / —z z—Vo <5 vr a /    I 1 p 24- [(3 -fluoro-2-methoxyphenyl)amino] -8-oxa-5 ,12,13,14,19,23-hexaazapentacyclo[ 19.2.1.112,15. 02,7.017,22]-pentacosa-1 (24),2,4,6,13,15(25),21 -he ptaen-20-one 42 F Q-o \ \ 0    NH \ H /     ° °=x   / N 25-[(3-fluoro-2-methoxyphenyl)amino]-18-oxa-1,6,10,15-tetraazapentacyclo[18.3.1.18,11.04,9.012,1 7]-pentacosa-8,11 (25), 12,14,16-pentaene-2,7-dio ne2023257355   28 May 2026# Structure IUPAC name 43 F Q-o7 Q    NH V'N k / I      H r         °\ *—0   / 0      x-- 28-[(3 -fluoro-2-methoxyphenyl)amino] -3,21-di oxa-6,11,15,23-tetraazapentacyclo[21.3.1.110,13.0 4,9.012,17]-octacosa-4,6,8,10(28), 12-pentaene-14,2 2-dione 44 I °A \_ / \=O A ^A'o / Y 1 < " C ) Z^ 27-[(3-fluoro-2-methoxyphenyl)amino]-3,20-di oxa-6,11,15,22-tetraazapentacyclo[20.3.1.110,13.0 4,9.012,17]-heptacosa-4,6,8,10(27), 12-pentaene-14, 21-dione 70 o / \  1 Vs \      U ° \ / —\ ° Z— /   \ / T 26-[(3-fluoro-2-methoxyphenyl)amino]-20-oxa-2,5,10,14-tetraazapentacyclo [19.3.1.19,12.03,8.011,1 6]-hexacosa-1 (25),3,5,7,9(26), 11,21,23-octaen-1 3-one5962023257355   28 May 2026Ul d ? H 2 dAA HN J d / 0 H ) MZ \fl 1 \_ / yJ<.NH HN J d 9 hnltS^ NZ \ 1 H 1 J         NH Structure 27- [(3 -fluoro-2-methoxyphenyl)amino] -17-oxa-5,9,14,22-tetraazapentacyclo[20.2.2.17’1°.03’8.011’1 6]-heptacosa-7,10(27), 11,13,15-pentaen-6-one 27- [(3 -fluoro-2-methoxyphenyl)amino] -17-oxa-5,9,14,22-tetraazapentacyclo[20.3.1.1 ^.0^.011,1 6]-heptacosa-7,10(27), 11,13,15-pentaen-6-one 27-[(3-fluoro-2-methoxyphenyl)amino]-21 -oxa-2,5,10,14-tetraazapentacyclo[20.3.1.19,12.03’8.011’1 6]-heptacosa-1 (26),3,5,7,9(27), 11,22,24-octaen- 13-one IUPAC name2023257355   28 May 2026# Structure IUPAC name 77 F ry °\ X NH hn^AtA L I >—( / r\ uy 0 27-[(3 -fluoro-2-methoxyphenyl)amino] -17-oxa-5,9,14,22-tetraazapentacyclo[20.2.2.17,10.03,8.011,1 6]-heptacosa-7,10(27), 11,13,15-pentaene-6,21 -di one 78 F ry °\ X NH lD—( / Az'^N    A— AH °~ 0 27-[(3-fluoro-2-methoxyphenyl)amino]-17,20-d ioxa-5,9,14,22-tetraazapentacyclo[20.2.2.17,10.03, 8.011,16]-heptacosa-7,10(27), 11,13,15-pentaene-6, 21 -dione 79 z o Z Oxi   1 \ Z.A    o n ‘At n a ^z o=< Y /  \ z— /     J x      x— 27-[(3-fluoro-2-methoxyphenyl)amino]-17,20-d ioxa-5,9,14,22-tetraazapentacyclo[20.3.1.17,10.03, 8.011,16]heptacosa-7,10(27), 11,13,15-pentaene-6, 21-dione2023257355   28 May 2026# Structure IUPAC name 80 F CXo A \ 9 NH L JI / —\\ ,N n y_ / \ H / / 0 25-[(3-fluoro-2-methoxyphenyl)amino]-18-oxa-1,6,10,15-tetraazapentacyclo[18.2.2.18,11.04,9.012,1 7]-pentacosa-8,11 (25), 12,14,16-pentaen-7-one 81 F C>0 A \ 9    NH hn^vA / =A I X / a / / N \ H / / 0 o=X / \ J N 25-[(3-fluoro-2-methoxyphenyl)amino]-18-oxa-1,6,10,15-tetraazapentacyclo[18.2.2.18,11.04,9.012,1 7]-pentacosa-8,11 (25), 12,14,16-pentaene-2,7-dio ne 82 F Cx° A \ 9 nh HN^rr\< L JI / —\\ zN V-# H       / J       0 26-[(3 -fluoro-2-methoxyphenyl)amino] -3 -oxa-6 ,11,15,21 -tetraazapentacyclo [19.2.2.110,13.04,9.012, 17]-hexacosa-4,6,8,10(26), 12-pentaen-14-one2023257355   28 May 2026# Structure IUPAC name 83 F A \ 9    NH HN^TrA L A / / N V- / I H 1 J      0 A 1 0 28-[(3 -fluoro-2-methoxyphenyl)amino] -3,21-di oxa-6,11,15,23-tetraazapentacyclo[21.2.2.110,13.0 4,9.012,17]-octacosa-4,6,8,10(28),12-pentaene-14,2 2-dione 84 F CKo \ \ 9 NH hn^ttA / ==^ L A / A / / N H / 1              °\ vCj 0 27-[(3 -fluoro-2-methoxyphenyl)amino] -3,20-di oxa-6,11,15,22-tetraazapentacyclo[20.2.2.110,13.0 4,9.012,17]-heptacosa-4,6,8,10(27),12-pentaene-14, 21-dione 91 c» \ J            /    ) \        ZI    z— ° \   / —\   / Z— /   \< I         \ (20 Z)-28-[(3 -fluoro-2-methoxyphenyl)amino] -2 0-methyl-3-oxa-6,11,15,23-tetraazapentacyclo[2 1.3.1.110,13.04,9.012,17]-octacosa-4,6,8,10(28), 12,2 0-hexaen-14-one2023257355   28 May 2026# Structure IUPAC name 92 hn^vA L A / A / / N V- / /      H      | \ °> \—N   / (20 E)-28-[(3-fluoro-2-methoxyphenyl)amino]-2 0-methyl-3-oxa-6,11,15,23-tetraazapentacyclo[2 1.3.1.110,13.04,9.012,17]-octacosa-4,6,8,10(28),12,2 0-hexaen-14-one 93 1 ( / \          ZI     Z—' ° \ / —\   / I         \ 28-[(3-fluoro-2-methoxyphenyl)amino]-20-meth yl-3-oxa-6,11,15,23-tetraazapentacyclo[21.3.1.1 10,13.04,9.012,17]-octacosa-4,6,8,10(28), 12-pentaen-14-one 94 ,F 9 hn-^Q,, / / =\ I 1 / —\\ / N N Y-M H / 27-[(3 -fluoro-2-methoxyphenyl)amino] -3 -oxa-6 ,11,15,22-tetraazapentacyclo[20.3.1.110,13.04,9.012, 17]-heptacosa-4,6,8,10(27), 12,19-hexaene-14,21-dione2023257355   28 May 2026# Structure IUPAC name 95 / =\ i A / \ / V^N    / I H / 27-[(3-fluoro-2-methoxyphenyl)amino]-3-oxa-6 ,11,15,22-tetraazapentacyclo[20.3.1.110,13.04,9.012, 17]-heptacosa-4,6,8,10(27), 12-pentaene-14,21 -di one 96 —0 f 9 y— T H 6 n 0      \ (19 Z)-28-[(3-fluoro-2-methoxyphenyl)amino]-3 -oxa-6,11,15,23-tetraazapentacyclo[21.3.1.110,13. 04,9.012,17]-octacosa-4,6,8,10(28), 12,19-hexaene-14,22-dione 97 z U-'V^\ (l   1 (JX I ° \   / — / Z— / I (19 E )-28-[(3-fluoro-2-methoxyphenyl)amino]-3 -oxa-6,11,15,23-tetraazapentacyclo[21.3.1.110,13. 04,9.012,17]-octacosa-4,6,8,10(28), 12,19-hexaene-14,22-dione2023257355   28 May 2026# Structure IUPAC name 98 ZF 9 VS-O T H o i 0 \ 28-[(3-fluoro-2-methoxyphenyl)amino]-3-oxa-6 ,11,15,23-tetraazapentacyclo[21.3.1.110,13.04,9.012, 17]-octacosa-4,6,8,10(28),12-pentaene-14,22-dio ne 102 T Z—< O= /         \ °\J \ JO o 24-[(3-fluoro-2-methoxyphenyl)amino]-8-oxa-5 ,11,12,13,19,23-hexaazapentacyclo [19.2.1.110,13. 02,7.017,22]-pentacosa-1 (24),2,4,6,10(25), 11,21 -he ptaen-20-one 103 F J^JD^ J-|H 0 N 1 \    / /     NH hn-a / 0 \ N-Nz 25-[(3-fluoro-2-methoxyphenyl)amino]-8-oxa-5 ,11,12,13,20,24-hexaazapentacyclo[20.2.1.110,13. 02,7.018,23]-hexacosa-1 (25),2,4,6,10(26), 11,22-he ptaen-21-one2023257355   28 May 2026# Structure IUPAC name 107 F T j 0 / Vt-C zN hn। uH y NH MI / 24-[(3-fluoro-2-methoxyphenyl)amino]-2,5,10,1 4-tetraazapentacyclo [17.3.1.19,12.03,8.011,16] -tetrac osa-1 (23),3,5,7,9(24), 11,19,21 -octaen- 13-one 112 z La /     T^'Ok 011  ^-""l "PCh1 / ^° O=(  2—< / —z z— /   X   ) i      \__ / 27-[(3 -fluoro-2-methoxyphenyl)amino] -17-oxa-5,9,14,22-tetraazapentacyclo[20.3.1.17,10,03,8.011,1 6]-heptacosa-7,10(27), 11,13,15-pentaene-6,21 -di one 116 A 9 L / L / \\ / n I H / / ° aa 0 25-[(3 -fluoro-2-methoxyphenyl)amino] -7,8,9,10 ,14,15,18,18a,19,20-decahydro-6H-7,11 -methan o-22,24-methenodipyrido[3,4-b:4',3'-f] [1,5,15]o xadiazacycloicosine-12,21(13H,23H)-dione2023257355   28 May 2026# Structure IUPAC name 117 V\ 9 I A / \\ / N I H / / ° v^O 0 Z-25-[(3-fluoro-2-methoxyphenyl)amino]-7,8,9, 10,14,15,18,18a, 19,20-decahydro-6H-7,11 -meth ano-22,24-methenodipyrido[3,4-b:4',3'-f] [1,5,15 ]oxadiazacycloicosine-12,21(13H,23H)-dione 118 V\ 9 hn^vAv / 7^ I A / \\ / N H / / ° 0 E -25-[(3 -fluoro-2-methoxyphenyl)amino] -7,8,9, 10,14,15,18,18a,19,20-decahydro-6H-7,11 -meth ano-22,24-methenodipyrido[3,4-b:4',3'-f] [1,5,15 ]oxadiazacycloicosine-12,21(13H,23H)-dione2023257355   28 May 2026# Structure IUPAC name / 0 F 0 HN J 119 HN^ H / 0 —  —r\ / N 25-[(3-fluoro-2-methoxyphenyl)amino]-7,8,9,10 ,14,15,16,17,18,18a,19,20-dodecahydro-6H-7,1 1-methano-22,24-methenodipyrido[3,4-b:4',3'-f] [1,5,15]oxadiazacycloicosine-12,21(13H,23H)-d ione w 0 f r 11 1 120 0 HN^ NH rVX H \ N _J 22-(3-fluoro-2-methoxyanilino)-7,8,9,10,13,14, 15,15a,16,17-decahydro-6H, 12H-7,11 -methano-19,21 -(metheno)dipyrido[3,4-b:4',3'-f] [1,5,12]o xadiazacycloheptadecin-18(20H)-one n y F 0 NH 121 HN^ rVx H C) '—iZ / N 22-(3-fluoro-2-methoxyanilino)-7,8,9,10,15,15a, 16,17-octahydro-6H, 12H-7,11 -methano-19,21-( metheno)dipyrido[3,4-b:4',3'-f][1,5,12]oxadiaza cycloheptadecin-18(20H)-one2023257355   28 May 2026# Structure IUPAC name 122 9 hn / |T\k / ^\ I X / 4 zn I H / J         0 \__ 20-(3 -fluoro-2-methoxyanilino)-7,8,13,13a,14,1 5-hexahydro-6H, 10H-7,9-methano-17,19-(meth eno)dipyrido[3,4-b:4',3'-f][1,5,12]oxadiazacyclo pentadecin-16(18H)-one 123 Jr 9 hn-XX HN'yA L X / \\ , n 1 H / J        0 X^nCT^ 20-(3-fluoro-2-methoxyanilino)-7,8,11,12,13,13 a, 14,15-octahydro-6H, 10H-7,9-methano-17,19-( metheno)dipyrido[3,4-b:4',3'-f] [1,5,12] oxadiaza cyclopentadecin-16( 18H)-one 124 °x 9 hnxxKsY^v 1 X / A ,N V^N V / 1 H / J      0 21 -(3-fluoro-2-methoxyanilino)-7,8,10,11,14,14 a,15,16-octahydro-6H-7,9-methano-18,20-(meth eno)dipyrido[3,4-b:4',3'-f] [1,5,13] oxadiazacyclo hexadecin-17(19H)-one2023257355   28 May 2026# Structure IUPAC name 125 v( 9 I A / v ,n 1 H / J       0 21 -(3-fluoro-2-methoxyanilino)-7,8,10,11,12,13 ,14,14a,15,16-decahydro-6H-7,9-methano-18,20 -(metheno)dipyrido [3,4-b:4',3'-f] [1,5,13] oxadiaz acyclohexadecin-17(19H)-one 129 1 f Oxa 9  HN"^^ Hrr$-PN J H 0 Cd 24-(3-fluoro-2-methoxyanilino)-7,8,9,10,13,14, 15,16,17,17a,18,19-dodecahydro-6H, 12H-7,11 -methano-21,23-(metheno)dipyrido[3,4-b:4',3'-f][ 1,5,14]oxadiazacyclononadecin-20(22H)-one 131 F T J 2   HN'''^''^ hn^AtA i I >AN A^~N J H 0 0 \ NA 20-(3-fluoro-2-methoxyanilino)-6,7,9,10,13,13a, 14,15-octahydro-12H-8,11 -ethano-17,19-(methe no)dipyrido[3,4-j :4',3'-n] [ 1,4,7,12]oxatriazacycl opentadecine-12,16(18H)-dione2023257355   28 May 2026# Structure IUPAC name 135 F o Xj Hf n-pN H 0 21 -(3-fluoro-2-methoxyanilino)-6,7,8,9,14,14a, 1 5,16-octahydro-11H-7,10-ethano-18,20-(methen o)dipyrido[3,4-b:4',3'-f][1,5,12]oxadiazacyclohe xadecin-17(19H)-one 136 F o AJ 0 HN HnAA / ^., l A / A / T H o 21 -(3-fluoro-2-methoxyanilino)-6,7,8,9,12,13,1 4,14a,15,16-decahydro-11 H-7,10-ethano-18,20-(metheno)dipyrido [3,4-b:4',3'-f] [1,5,12]oxadiaz acyclohexadecin-17(19H)-one 137 / F 0     / 2 HnA^J QH z /    H     / \ °\ CL        /      / A      N 28-(3-fluoro-2-methoxyanilino)-1,2,13,14,16,17 ,18,19,20,21,23,24,25,25a-tetradecahydro-12H-12,15-ethano-4,6-(metheno)dipyrido[3,4-b:4',3'-f][1,11,5,18]dioxadiazacyclohenicosin-3(5H)-on e2023257355   28 May 2026# Structure IUPAC name 139 of 9 hn / itA l A / \\ / ,N y_ / 1 H / / 0 19-(3-fluoro-2-methoxyanilino)-6,7,8,9,12,12a, 1 3,14-octahydro- 11H-8,10-methano-16,18-(meth eno)dipyrido[3,4-b:4',3'-f][1,5,10]oxadiazacyclo tetradecine-11,15(17H)-dione 142 ..... "A j ° \ / —\ / — z— / \-- / I 23-(3 -fluoro-2-methoxyanilino)-12,13,14,15,16, 16a,17,18-octahydro-6H, 11H-10,7:20,22-di(met heno)dipyrido[3,4-m:4',3'-q][1,4,5,6,15]oxatetra azacyclooctadecin-19(21 H)-one 146 z —\ °   T             ZX / \ O=\ X o (16aS)-23-(3-fluoro-2-methoxyanilino)-14,15,1 6a,17,18,19,22,22a-octahydro-2H, 12H-4,6-(met heno)dipyrido[3,4-k:4',3'-o]pyrrolo[2,1-g][1,5,8, 13 ] oxatriazacyclohexadecine-3,16,21(1H,5H,13 H)-trione2023257355   28 May 2026# Structure IUPAC name 147 1 f XJ 0 HN hn^vA L I M / I H / 1 0        1 / N / z I ) \ / N \___ /      H (16aS,22aS)-23-(3-fluoro-2-methoxyanilino)-14 ,15,16a,17,18,19,22,22a-octahydro-2H, 12H-4,6-(metheno)dipyrido[3,4-k:4',3'-o]pyrrolo[2,1-g][1 ,5,8,13] oxatriazacyclohexadecine-3,16,21(1H,5 H,13H)-trione 148 f Tj 0 t aW> J—# °\ 1 0 1 A J \ / N \___ / H (16aS,22aR)-23-(3-fluoro-2-methoxyanilino)-14 ,15,16a,17,18,19,22,22a-octahydro-2H, 12H-4,6-(metheno)dipyrido[3,4-k:4',3'-o]pyrrolo[2,1-g][1 ,5,8,13] oxatriazacyclohexadecine-3,16,21(1H,5 H,13H)-trione 151 1 f °'T1 0 HN hnl xVf^N T H / X 0 23-(3-fluoro-2-methoxyanilino)-6,7,8,9,12,13,1 6,16a,17,18-decahydro- 15H-11,14-ethano-20,22 -(metheno)dipyrido [3,4-b:4',3'-f][1,5,10,15] oxat riazacyclooctadecine-10,15,19(11 H,21 H)-trione2023257355   28 May 2026# Structure IUPAC name 153 V\ 9 hn^v\. / ^x l X / 4 ,n T QJ 23-(3-fluoro-2-methoxyanilino)-6,7,9,10,12,13, 16,16a, 17,18-decahydro-15H-11,14-ethano-20,2 2-(metheno)dipyrido[3,4-m:4',3'-q] [ 1,4,7,10,15] dioxatriazacyclooctadecine-15,19(21 H)-dione trifluoroacetic acid (1\1) 155 VA 9 hn^Q_ / I X / 4 n X__ / / I H / 7      ° —t / (7S, 15aS)-22-(3-fluoro-2-methoxyanilino)-6,7,9 ,10,13,14,15,15a,16,17-decahydro-12H-7,11 -me thano-19,21 -(metheno)dipyrido[3,4-l:4',3'-p] [ 1,4 ,7,14]dioxadiazacycloheptadecin-18(20H)-one 156 VA 9 hn / tA L X / A n X__ ■    H / = 0 —N\ (7S, 15aR)-22-(3-fluoro-2-methoxyanilino)-6,7,9 ,10,13,14,15,15a,16,17-decahydro-12H-7,11 -me thano-19,21 -(metheno)dipyrido[3,4-l:4',3'-p] [ 1,4 ,7,14]dioxadiazacycloheptadecin-18(20H)-one2023257355   28 May 2026# Structure IUPAC name 157 hn^VA / ==\ 1 X / \X N I H / 1       0 (7S,14aS)-21 -(3 -fluoro-2-methoxyanilino)-6,7,9 ,10,12,13,14,14a,15,16-decahydro-7,11 -methan o-18,20-(metheno)dipyrido[3,4-k:4',3'-o] [ 1,4,7,1 3 ] dioxadiazacyclohexadecin-17(19H)-one 158 9 HN-X^J I X / A n £    H / = 0 ^XX* (7S,14aR)-21 -(3 -fluoro-2-methoxyanilino)-6,7,9 ,10,12,13,14,14a,15,16-decahydro-7,11 -methan o-18,20-(metheno)dipyrido[3,4-k:4',3'-o] [ 1,4,7,1 3 ] dioxadiazacyclohexadecin-17(19H)-one 160 9 HN--X^__ / hn iX / ==\ l A / ¾ / N   >—7 T H 19-(3-fluoro-2-methoxyanilino)-7,8,10,11,12,12 a,13,14-octahydro-6H-7,9-methano-16,18-(meth eno)dipyrido[3,4-b:4',3'-f][1,5,11]oxadiazacyclo tetradecin-15(17H)-one2023257355   28 May 2026# Structure IUPAC name 161 9 i A / \ / \Xn V- / T H o 20-(3-fluoro-2-methoxyanilino)-6,7,8,9,11,12,1 3,13a,14,15-decahydro-7,10-methano-17,19-(m etheno)dipyrido[3,4-b:4',3‘-f][1,5,11]oxadiazacy clopentadecin-16(18H)-one 162 ^°vX 9 HnX^___J HnAA / X, L A / \ / \Xn I H of XQ (7R, 13aS)-20-(3-fluoro-2-methoxyanilino)-6,7,8 ,9,11,12,13,13a,14,15-decahydro-7,10-methano-17,19-(metheno)dipyrido[3,4-b:4',3'-f] [1,5,11]o xadiazacyclopentadecin-16( 18H)-one 163 9 hnA^j hn'x>tX Ul>-o H °\ XQ (7R, 13aR)-20-(3-fluoro-2-methoxyanilino)-6,7, 8,9,11,12,13,13a,14,15-decahydro-7,10-methan o-17,19-(metheno)dipyrido [3,4-b:4',3'-f] [1,5,11] oxadiazacyclopentadecin-16(18H)-one2023257355   28 May 2026# Structure IUPAC name 165 z II 1 y) V-°v\ / — Z—' I 19-(3-fluoro-2-methoxyanilino)-7,8,10,11,12,12 a,13,14-octahydro-6H-6,9-methano-16,18-(meth eno)dipyrido[3,4-b:4',3'-f] [1,5,11]oxadiazacyclo tetradecin-15(17H)-one 166 z II 1 AY t'Va " M ° \ / — z—' I 20-(3-fluoro-2-methoxyanilino)-6,7,8,9,11,12,1 3,13a,14,15-decahydro-6,10-methano-17,19-(m etheno)dipyrido[3,4-b:4',3'-f][1,5,11]oxadiazacy clopentadecin-16(18H)-one 167 Y 9 hn^Ya_ / ^\ I JL / A / N I H / \ °\ N—f (12aR, 19aS)-20-(3 -fluoro-2-methoxyanilino)-1, 2,12a,13,14,15,17,18,19,19a-decahydro-12H-4, 6-(metheno)dipyrido[3,4-h:4',3'-l]pyrrolo[2,1-c] [1,4,10]oxadiazacyclotridecin-3(5H)-one2023257355   28 May 2026# Structure IUPAC name 168 Jr 9 I X / A / N -     H / __   0 N—( (12aR, 19aR )-20-(3 -fluoro-2-methoxyanilino)-1, 2,12a,13,14,15,17,18,19,19a-decahydro-12 H-4, 6-(metheno)dipyrido[3,4-h :4',3'-1 ]pyrrolo[2,1-c ] [ 1,4,10]oxadiazacyclotridecin-3(5 H)-one 169 Jr 9 / ^\ I X /     N V^N  \ I H / \ 0 (12aS, 19aS)-20-(3-fluoro-2-methoxyanilino)-1,2 ,12a,13,14,15,17,18,19,19a-decahydro-12 H-4,6-(metheno)dipyrido[3,4-h :4',3'-1 ]pyrrolo[2,1- c ][1, 4,10]oxadiazacyclotridecin-3(5 H)-one 170 Jr 9 hn / |i\v / ^\ I X / 1 ZN -     H / \ ° (12a S, 19aR )-20-(3-fluoro-2-methoxyanilino)-1, 2,12a,13,14,15,17,18,19,19a-decahydro-12 H-4, 6-(metheno)dipyrido[3,4-h :4',3'-1 ]pyrrolo[2,1-c ] [ 1,4,10]oxadiazacyclotridecin-3(5 H)-oneor a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof.2023257355   28 May 202619. A pharmaceutical composition comprising a compound of any one of claims 1-18 or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof, and a pharmaceutically acceptable carrier.

20. The pharmaceutical composition of claim 19, further comprising one or more additional pharmaceutically active agents.

21. A method of inhibiting of EGFR kinase activity in a cell, comprising contacting the cell with a compound of any one of claims 1-18 or a pharmaceutical composition of claim 19 or 20.

22. The method of claim 21, wherein the contacting is in vitro or in vivo.

23. A method for the treatment, mitigation, or prevention of a disease or disorder associated with EGFR kinase activity comprising administering to a subject in need thereof a compound of any one of claims 1-18 or a pharmaceutical composition of claim 19 or 20.

24. The method of claim 23, wherein the disease or disorder is selected from hyperproliferative diseases and / or disorders responsive to induction of cell death.

25. The method of claim 23, wherein the disease or disorder is selected from the group consisting of Lung Cancer; Lung Cancer Susceptibility 3 (LNCR3); Lung Squamous Cell Carcinoma; Gliosarcoma; Brain Stem Glioma; Adenocarcinoma; Colorectal Cancer; Glioblastoma; Breast Cancer; Squamous Cell Carcinoma; Small Cell Cancer of the Lung; Lung Squamous Cell Carcinoma; Inflammatory Skin and Bowel Disease, Neonatal, 2; Gastric Cancer; Prostate Cancer; Squamous Cell Carcinoma, Head and Neck; Pancreatic Cancer; Brain Cancer; Ovarian Cancer; Esophageal Cancer; Giant Cell Glioblastoma; Gliosarcoma; Lung Benign Neoplasm; Glioma; Exanthem; Endometrial Cancer; Adenoid Cystic Carcinoma; Bladder Cancer; Cowden Syndrome 1; Bronchiolo-Alveolar Adenocarcinoma; Oligodendroglioma; Hepatocellular Carcinoma; Lung Non-Squamous Non-Small Cell Carcinoma; High Grade Glioma; Glial Tumor; Laryngeal Squamous Cell Carcinoma; Renal Cell Carcinoma, Nonpapillary; Chronic Kidney Disease; Nasopharyngeal Carcinoma; Oral Squamous Cell Carcinoma; Lung Disease; Interstitial Lung Disease; Adenosquamous Lung Carcinoma; Bile Duct Cancer; Meningioma, Familial; Small Cell Carcinoma; Tumor Predisposition Syndrome; Pancreatic Adenocarcinoma; Diarrhea; Breast Ductal Carcinoma.2023257355   28 May 202626. The method of claim 25, wherein the disease or disorder is lung cancer.

27. The method of any one of claims 23-26, wherein the subject is a mammal.

28. The method of claim 27, wherein the subject is a human.