Substituted 3,4-dihydroquinolinone inhibitors of tshr

Abstract

Disclosed are compounds that are thyroid stimulating hormone receptor antagonists, and methods useful for preventing or treating a thyroid disease.

Description

[0001] SUBSTITUTED 3,4-DIHYDROQUINOLINONE INHIBITORS OF TSHR CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Application No. 63 / 393,411, filed July 29, 2022; the contents of which are hereby incorporated by reference in their entirety. BACKGROUND About 40% of hyperthyroidism patients suffer from Graves' disease (Morbus Basedow), an autoimmune disease in which autoantibodies activate the thyrotropin receptor, mimicking its natural hormone ligand, the thyroid-stimulating hormone (TSH). This pathological activation of TSH-Receptor (TSHR) leads to uncontrolled production of thyroid hormones (e.g., T3 and T4) causing hyperthyroidism. TSH and the TSHR are important proteins for controlling thyroid function. TSHR is primarily expressed in follicular epithelial cells of the thyroid gland, but also is expressed in a variety of additional cell types, such as retro-orbital fibroblasts, kidney cells, adipocytes and bone cells. TSH binds to its receptor and leads to the stimulation of second messenger pathways involving predominantly cAMP. Inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG) pathways are also activated at higher TSH concentrations. The treatment of choice applied in the clinics for decades involves thyrostatic drugs that block the production of thyroid hormones. These medications play a role further downstream in the signal cascade of the thyroid upon activation of the TSHR. Since thyroid hormones T3 and T4 are secreted in the thyroid gland, thyrostatic drugs induce an inhibition of their synthesis. Thus, the current primary anti-thyroid treatment does not target the causative molecular activation of the TSHR by autoantibodies and patients are therefore burdened by a rate of at least 5% adverse effects. This demands frequent controls of the thyroid hormone levels and adjustments of thyrostatics dosage. In contrast to these drugs, which regulate the thyroid hormone level, another promising target is the TSHR itself. However, small allosteric antagonists acting directly at the TSHR are not available on the market yet. Additionally, about 25% of Graves' disease patients also develop an orbitopathy referred to as “Graves' ophthalmopathy”, a related organ-specific autoimmune disease affecting the appearance and functioning of the eyes. There is considerable evidence that expression of the TSHR in the orbital fibroblasts and orbital adipocytes behind the eye may contribute to this difficult-to-treat orbitopathy, and thyroid stimulating antibodies titer tend to correlate with severity of Grave’s ophthalmopathy. Orbital fibroblast has been recognized as primary target cells of autoimmune attack and TSHR acts as a primary autoantigen in Grave’s ophthalmopathy. The pathological activation of TSHR leads to the production of the extracellular matrix by involvement of hyaluronanic acid, fibrosis and swelling of extraocular muscle as well as adipogenesis of orbital fibroblasts (orbital fat expansion). The increase in tissue volume in the orbit often causes diplopia and compression of the optic nerve and exophthalmos. Thus, the TSHR is also potential target for pharmacological intervention of Grave’s ophthalmology and thyroid eye disease. Accordingly, there is a need in the art to provide additional means for the treatment of hyperthyroidism, in particular compounds that act as TSHR antagonists. SUMMARY One aspect of the invention provides compounds, compositions, and methods useful for preventing or treating a thyroid disease, such as hyperthyroidism, Grave’s disease, Grave’s opthalmopathy, or thyroid eye disease. Accordingly, provided herein in some embodiments is a compound having the structure of Formula (I): or a pharmaceutically acceptable salt thereof, wherein: A is (C6-C10)aryl, 5- to 10-membered heteroaryl, (C3-C8)cycloalkyl, or 4- to 7-membered heterocycloalkyl; n is 0, 1, 2, 3, 4, or 5; R1is independently for each occurrence (C1-C6)alkyl, (C2-C6)alkynyl, (C2-C6)alkenyl, (C3- C8)cycloalkyl, (C3-C8)cycloalkoxy, (C6-C10)aryl, (C6-C10)aryloxy, (C6-C10)aryl(C1-C6)alkyl, 4- to 7-membered heterocycloalkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl, halo, cyano, amino, formyl, carboxy, or alkoxycarbonyl, wherein (C1-C6)alkyl, (C2-C6)alkynyl, (C2-C6)alkenyl, (C3-C8)cycloalkyl, C3-C8)cycloalkoxy, (C6-C10)aryl, (C6-C10)aryloxy, (C6-C10)aryl(C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl, and 4- to 7-membered heterocycloalkyl are each optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, 4- to 7-membered heterocycloalkyl, 5- to 6- membered heteroaryl, (C1-C6)alkoxy, (C1-C6)haloalkoxy, (C1-C6)fluoroalkoxy, 5- to 6-membered heteroaryloxy, or two vicinal occurrences of R1taken together with the atoms to which they are attached form a fused 5- to 7-membered cycloalkyl, 5- to 7-membered heterocycloalkyl ring, 5- to 6- membered heteroaryl ring or phenyl ring, any of which is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1- C6)alkyl, (C1-C6)haloalkyl (C3-C8)cycloalkyl, and (C1-C6)alkoxy; Q is N or CR2c; R2a, R2b, and R2c, are each independently hydrogen, halo, cyano, (C1-C6)alkyl, or (C3- C8)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; R3is (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C6)alkyl), (C6-C10)aryl, (C6- C10)aryl(C1-C6)alkyl), or 4- to 7-membered heterocycloalkyl; each of which is optionally substituted with one or more substituents independently selected from halo, cyano, (C1- C6)haloalkyl, hydroxy, (C1-C6)alkoxy(C1-C6)alkyl, and (C1-C6)alkoxy; X and Z are independently NR4, C(R5)2, or O; R4and R5independently for each occurrence hydrogen or (C1-C6)alkyl, wherein (C1- C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy, or when Z is NR4, R3and R4taken together with the nitrogen to which they are attached form a 4- to 7-member heterocycloalkyl optionally substituted with one or more (C1-C6)alkyl or halo; L is (C1-C6)alkylene optionally substituted with one or more substituents independently selected from halo, hydroxy, C1-C6)alkoxy, and cyano; W represents: –C(R6)2–C(R7)2–, –C(R7)2–, –O–C(R8)2–, –C(R8)2–O–, –C(R8)2–NR9–, –N=C(R10) –, or –O–; and R6, R7, R8, R9and R10are independently for each occurrence hydrogen, (C1-C6)alkyl,or NH2, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, cyano, hydroxy, (C1-C6)alkoxy(C1-C6)alkyl, and (C1-C6)alkoxy. In some embodiments a compound has the structure of Formula (II): or a pharmaceutically acceptable salt thereof, wherein A is (C6-C10)aryl, 5- to 10-membered heteroaryl, (C3-C8)cycloalkyl, or 4- to 7-membered heterocycloalkyl; n is 0, 1, 2, 3, 4, or 5; R1is independently for each occurrence (C1-C6)alkyl, (C2-C6)alkynyl, (C2-C6)alkenyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkoxy, (C6-C10)aryl, (C6-C10)aryloxy, (C6-C10)aryl(C1-C6)alkyl, 4- to 7-membered heterocycloalkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl, halo, cyano, amino, formyl, carboxy, or alkoxycarbonyl, wherein (C1-C6)alkyl, (C2-C6)alkynyl, (C2-C6)alkenyl, (C3-C8)cycloalkyl, C3- C8)cycloalkoxy, (C6-C10)aryl, (C6-C10)aryloxy, (C6-C10)aryl(C1-C6)alkyl, (C1-C6)alkoxy, (C1- C6)alkoxy(C1-C6)alkyl, and 4- to 7-membered heterocycloalkyl are each optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, 4- to 7-membered heterocycloalkyl, 5- to 6- membered heteroaryl, (C1-C6)alkoxy, (C1-C6)haloalkoxy, (C1-C6)fluoroalkoxy, 5- to 6-membered heteroaryloxy, or two vicinal occurrences of R1taken together with the atoms to which they are attached form a fused 5- to 7-membered cycloalkyl, 5- to 7-membered heterocycloalkyl ring, 5- to 6- membered heteroaryl ring or phenyl ring, any of which is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C1-C6)haloalkyl (C3-C8)cycloalkyl, and (C1-C6)alkoxy; Q is N or CR2c; R2a, R2b, and R2c, are each independently hydrogen, halo, cyano, (C1-C6)alkyl, or (C3- C8)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; R3is (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C6)alkyl), (C6-C10)aryl, (C6- C10)aryl(C1-C6)alkyl), or 4- to 7-membered heterocycloalkyl; each of which is optionally substituted with one or more substituents independently selected from halo, cyano, (C1-C6)haloalkyl, hydroxy, (C1-C6)alkoxy(C1-C6)alkyl, and (C1-C6)alkoxy; X and Z are independently NR4, C(R5)2, or O; R4and R5independently for each occurrence hydrogen or (C1-C6)alkyl, wherein (C1- C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy, or when Z is NR4, R3and R4taken together with the nitrogen to which they are attached form a 4- to 7-member heterocycloalkyl optionally substituted with one or more (C1-C6)alkyl or halo; L is (C1-C6)alkylene optionally substituted with one or more substituents independently selected from halo, hydroxy, C1-C6)alkoxy, and cyano; W represents: –C(R6)2–C(R7)2–, –C(R7)2–, –O–C(R8)2–, –C(R8)2–O–, –C(R8)2–NR9–, –N=C(R10) –, or –O–; and R6, R7, R8, R9and R10are independently for each occurrence hydrogen, (C1-C6)alkyl,or NH2, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, cyano, hydroxy, (C1-C6)alkoxy(C1-C6)alkyl, and (C1-C6)alkoxy. In some embodiments a compound has the structure of Formula (III): or a pharmaceutically acceptable salt thereof, wherein: A is (C6-C10)aryl, 5- to 10-membered heteroaryl, (C3-C8)cycloalkyl, or 4- to 7-membered heterocycloalkyl; n is 0, 1, 2, 3, 4, or 5; R1is independently for each occurrence (C1-C6)alkyl, (C2-C6)alkynyl, (C2-C6)alkenyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkoxy, (C6-C10)aryl, (C6-C10)aryloxy, (C6-C10)aryl(C1-C6)alkyl, 4- to 7-membered heterocycloalkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl, halo, cyano, amino, formyl, carboxy, or alkoxycarbonyl, wherein (C1-C6)alkyl, (C2-C6)alkynyl, (C2-C6)alkenyl, (C3-C8)cycloalkyl, C3- C8)cycloalkoxy, (C6-C10)aryl, (C6-C10)aryloxy, (C6-C10)aryl(C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl, and 4- to 7-membered heterocycloalkyl are each optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, 4- to 7-membered heterocycloalkyl, 5- to 6- membered heteroaryl, (C1-C6)alkoxy, (C1-C6)haloalkoxy, (C1-C6)fluoroalkoxy, 5- to 6-membered heteroaryloxy, or two vicinal occurrences of R1taken together with the atoms to which they are attached form a fused 5- to 7-membered cycloalkyl, 5- to 7-membered heterocycloalkyl ring, 5- to 6- membered heteroaryl ring or phenyl ring, any of which is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C1-C6)haloalkyl (C3-C8)cycloalkyl, and (C1-C6)alkoxy; Q is N or CR2c; R2a, R2b, and R2c, are each independently hydrogen, halo, cyano, (C1-C6)alkyl, or (C3- C8)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; R3is (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C6)alkyl), (C6-C10)aryl, (C6- C10)aryl(C1-C6)alkyl), or 4- to 7-membered heterocycloalkyl; each of which is optionally substituted with one or more substituents independently selected from halo, cyano, (C1-C6)alkyl, (C1-C6)haloalkyl, hydroxy, (C1-C6)alkoxy(C1-C6)alkyl, and (C1-C6)alkoxy; X and Z are independently NR4, C(R5)2, or O; R4and R5independently for each occurrence hydrogen or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy, or when Z is NR4, R3and R4taken together with the nitrogen to which they are attached form a 4- to 7-member heterocycloalkyl optionally substituted with one or more (C1-C6)alkyl or halo, or when Z is C(R5)2, R3and one R5taken together with the carbon to which they are attached form a 4, (C3-C8)cycloalkyl optionally substituted with one or more (C1- C6)alkyl or halo; L is (C1-C6)alkylene optionally substituted with one or more substituents independently selected from halo, hydroxy, C1-C6)alkoxy, and cyano; R10is hydrogen, (C1-C6)alkyl,or NH2, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, cyano, hydroxy, (C1-C6)alkoxy(C1-C6)alkyl, and (C1-C6)alkoxy. 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 invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. Other features, objects, and advantages of the invention will be apparent from the detailed description, and from the claims. DETAILED DESCRIPTION Definitions For convenience, before further description of the present invention, certain terms employed in the specification, examples and appended claims are collected here. These definitions should be read in light of the remainder of the disclosure and understood as by a person of skill in the art. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary skill in the art. In order for the present invention to be more readily understood, certain terms and phrases are defined below and throughout the specification. The articles “a” and “an” are used herein to refer to one or to 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. The phrase “and / or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with “and / or” should be construed in the same fashion, i.e., “one or more” of the elements so conjoined. Other elements may optionally be present other than the elements specifically identified by the “and / or” clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, a reference to “A and / or B”, when used in conjunction with open-ended language such as “comprising” can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc. As used herein in the specification and in the claims, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating items in a list, “or” or “and / or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of” or “exactly one of,” or, when used in the claims, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e., “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.” “Consisting essentially of,” when used in the claims, shall have its ordinary meaning as used in the field of patent law. As used herein in the specification and in the claims, the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, “at least one of A and B” (or, equivalently, “at least one of A or B,” or, equivalently “at least one of A and / or B”) can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc. It should also be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one step or act, the order of the steps or acts of the method is not necessarily limited to the order in which the steps or acts of the method are recited. In the claims, as well as in the specification above, all transitional phrases such as “comprising,” “including,” “carrying,” “having,” “containing,” “involving,” “holding,” “composed of,” and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Only the transitional phrases “consisting of” and “consisting essentially of” shall be closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03. Certain compounds contained in compositions of the present invention may exist in particular geometric or stereoisomeric forms. In addition, polymers of the present invention may also be optically active. The present invention contemplates all such compounds, including cis- and trans-isomers, R- and S-enantiomers, diastereomers, (D)-isomers, (L)-isomers, the racemic mixtures thereof, and other mixtures thereof, as falling within the scope of the invention. Additional asymmetric carbon atoms may be present in a substituent such as an alkyl group. All such isomers, as well as mixtures thereof, are intended to be included in this invention. “Geometric isomer" means isomers that differ in the orientation of substituent atoms in relationship to a carbon-carbon double bond, to a cycloalkyl ring, or to a bridged bicyclic system. Atoms (other than H) on each side of a carbon- carbon double bond may be in an E (substituents are on opposite sides of the carbon- carbon double bond) or Z (substituents are oriented on the same side) configuration. "R," "S," "S*," "R*," "E," "Z," "cis," and "trans," indicate configurations relative to the core molecule. Certain of the disclosed compounds may exist in “atropisomeric” forms or as “atropisomers.” Atropisomers are stereoisomers resulting from hindered rotation about single bonds where the steric strain barrier to rotation is high enough to allow for the isolation of the conformers. The compounds of the invention may be prepared as individual isomers by either isomer-specific synthesis or resolved from a mixture of isomers. Conventional resolution techniques include forming the salt of a free base of each isomer of an isomeric pair using an optically active acid (followed by fractional crystallization and regeneration of the free base), forming the salt of the acid form of each isomer of an isomeric pair using an optically active amine (followed by fractional crystallization and regeneration of the free acid), forming an ester or amide of each of the isomers of an isomeric pair using an optically pure acid, amine or alcohol (followed by chromatographic separation and removal of the chiral auxiliary), or resolving an isomeric mixture of either a starting material or a final product using various well known chromatographic methods. If, for instance, a particular enantiomer of compound of the present invention is desired, it may be prepared by asymmetric synthesis, or by derivation with a chiral auxiliary, where the resulting diastereomeric mixture is separated and the auxiliary group cleaved to provide the pure desired enantiomers. Alternatively, where the molecule contains a basic functional group, such as amino, or an acidic functional group, such as carboxyl, diastereomeric salts are formed with an appropriate optically-active acid or base, followed by resolution of the diastereomers thus formed by fractional crystallization or chromatographic means well known in the art, and subsequent recovery of the pure enantiomers. Percent purity by mole fraction is the ratio of the moles of the enantiomer (or diastereomer) or over the moles of the enantiomer (or diastereomer) plus the moles of its optical isomer. When the stereochemistry of a disclosed compound is named or depicted by structure, the named or depicted stereoisomer is at least about 60%, about 70%, about 80%, about 90%, about 99% or about 99.9% by mole fraction pure relative to the other stereoisomers. When a single enantiomer is named or depicted by structure, the depicted or named enantiomer is at least about 60%, about 70%, about 80%, about 90%, about 99% or about 99.9% by mole fraction pure. When a single diastereomer is named or depicted by structure, the depicted or named diastereomer is at least about 60%, about 70%, about 80%, about 90%, about 99% or about 99.9% by mole fraction pure. When a disclosed compound is named or depicted by structure without indicating the stereochemistry, and the compound has at least one chiral center, it is to be understood that the name or structure encompasses either enantiomer of the compound free from the corresponding optical isomer, a racemic mixture of the compound or mixtures enriched in one enantiomer relative to its corresponding optical isomer. When a disclosed compound is named or depicted by structure without indicating the stereochemistry and has two or more chiral centers, it is to be understood that the name or structure encompasses a diastereomer free of other diastereomers, a number of diastereomers free from other diastereomeric pairs, mixtures of diastereomers, mixtures of diastereomeric pairs, mixtures of diastereomers in which one diastereomer is enriched relative to the other diastereomer(s) or mixtures of diastereomers in which one or more diastereomer is enriched relative to the other diastereomers. The invention embraces all of these forms. Structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds produced by the replacement of a hydrogen with deuterium or tritium, or of a carbon with a13C- or14C-enriched carbon are within the scope of this invention. The term “prodrug” as used herein encompasses compounds that, under physiological conditions, are converted into therapeutically active agents. A common method for making a prodrug is to include selected moieties that are hydrolyzed under physiological conditions to reveal the desired molecule. In other embodiments, the prodrug is converted by an enzymatic activity of the host animal. The phrase “pharmaceutically acceptable excipient” or “pharmaceutically acceptable carrier” as used herein means a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting the subject chemical from one organ or portion of the body, to another organ or portion of the body. Each carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation, not injurious to the patient, and substantially non- pyrogenic. Some examples of materials which can serve as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose, and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose, and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol, and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer’s solution; (19) ethyl alcohol; (20) phosphate buffer solutions; and (21) other non-toxic compatible substances employed in pharmaceutical formulations. In certain embodiments, pharmaceutical compositions of the present invention are non-pyrogenic, i.e., do not induce significant temperature elevations when administered to a patient. The term “pharmaceutically acceptable salts” refers to the relatively non-toxic, inorganic and organic acid addition salts of the compound(s). These salts can be prepared in situ during the final isolation and purification of the compound(s), or by separately reacting a purified compound(s) in its free base form with a suitable organic or inorganic acid, and isolating the salt thus formed. Representative salts include the hydrobromide, hydrochloride, sulfate, bisulfate, phosphate, nitrate, acetate, valerate, oleate, palmitate, stearate, laurate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, naphthylate, mesylate, glucoheptonate, lactobionate, and laurylsulphonate salts, and the like. (See, for example, Berge et al. (1977) “Pharmaceutical Salts”, J. Pharm. Sci.66:1-19.) In other cases, the compounds useful in the methods of the present invention may contain one or more acidic functional groups and, thus, are capable of forming pharmaceutically acceptable salts with pharmaceutically acceptable bases. The term “pharmaceutically acceptable salts” in these instances refers to the relatively non-toxic inorganic and organic base addition salts of a compound(s). These salts can likewise be prepared in situ during the final isolation and purification of the compound(s), or by separately reacting the purified compound(s) in its free acid form with a suitable base, such as the hydroxide, carbonate, or bicarbonate of a pharmaceutically acceptable metal cation, with ammonia, or with a pharmaceutically acceptable organic primary, secondary, or tertiary amine. Representative alkali or alkaline earth salts include the lithium, sodium, potassium, calcium, magnesium, and aluminum salts, and the like. Representative organic amines useful for the formation of base addition salts include ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine, and the like (see, for example, Berge et al., supra). The term “pharmaceutically acceptable cocrystals” refers to solid coformers that do not form formal ionic interactions with the small molecule. A “therapeutically effective amount” (or “effective amount”) of a compound with respect to use in treatment, refers to an amount of the compound in a preparation which, when administered as part of a desired dosage regimen (to a mammal, preferably a human) alleviates a symptom, ameliorates a condition, or slows the onset of disease conditions according to clinically acceptable standards for the disorder or condition to be treated or the cosmetic purpose, e.g., at a reasonable benefit / risk ratio applicable to any medical treatment. The term “prophylactic or therapeutic” treatment is art-recognized and includes administration to the host of one or more of the subject compositions. If it is administered prior to clinical manifestation of the unwanted condition (e.g., disease or other unwanted state of the host animal) then the treatment is prophylactic, (i.e., it protects the host against developing the unwanted condition), whereas if it is administered after manifestation of the unwanted condition, the treatment is therapeutic, (i.e., it is intended to diminish, ameliorate, or stabilize the existing unwanted condition or side effects thereof). The term “patient” or “subject” refers to a mammal in need of a particular treatment. In certain embodiments, a patient is a primate, canine, feline, or equine. In certain embodiments, a patient is a human. An aliphatic chain comprises the classes of alkyl, alkenyl and alkynyl defined below. A straight aliphatic chain is limited to unbranched carbon chain moieties. As used herein, the term “aliphatic group” refers to a straight chain, branched-chain, or cyclic aliphatic hydrocarbon group and includes saturated and unsaturated aliphatic groups, such as an alkyl group, an alkenyl group, or an alkynyl group. “Alkyl” refers to a fully saturated cyclic or acyclic, branched or unbranched carbon chain moiety having the number of carbon atoms specified, or up to 30 carbon atoms if no specification is made. For example, alkyl of 1 to 8 carbon atoms refers to moieties such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl, and those moieties which are positional isomers of these moieties. Alkyl of 10 to 30 carbon atoms includes decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, eicosyl, heneicosyl, docosyl, tricosyl and tetracosyl. In certain embodiments, a straight chain or branched chain alkyl has 30 or fewer carbon atoms in its backbone (e.g., C1-C30 for straight chains, C3-C30 for branched chains), and more preferably 20 or fewer. Alkyl goups may be substituted or unsubstituted. As used herein, the term “heteroalkyl” refers to an alkyl moiety as hereinbefore defined which contain one or more oxygen, sulfur, nitrogen, phosphorus, or silicon atoms in place of carbon atoms. As used herein, the term “haloalkyl” refers to an alkyl group as hereinbefore defined substituted with at least one halogen. As used herein, the term “hydroxyalkyl” refers to an alkyl group as hereinbefore defined substituted with at least one hydroxyl. As used herein, the term “alkylene” refers to an alkyl group having the specified number of carbons, for example from 2 to 12 carbon atoms, that contains two points of attachment to the rest of the compound on its longest carbon chain. Non-limiting examples of alkylene groups include methylene -(CH2)-, ethylene -(CH2CH2)-, n-propylene -(CH2CH2CH2)-, isopropylene - (CH2CH(CH3))-, and the like. Alkylene groups can be cyclic or acyclic, branched or unbranched carbon chain moiety, and may be optionally substituted with one or more substituents. "Cycloalkyl" means mono- or bicyclic or bridged or spirocyclic, or polycyclic saturated carbocyclic rings, each having from 3 to 12 carbon atoms. Preferred cycloalkyls have from 3-10 carbon atoms in their ring structure, and more preferably have 3-6 carbons in the ring structure. Cycloalkyl groups may be substituted or unsubstituted. As used herein, the term “halocycloalkyl” refers to an cycloalkyl group as hereinbefore defined substituted with at least one halogen. "Cycloheteroalkyl" refers to an cycloalkyl moiety as hereinbefore defined which contain one or more oxygen, sulfur, nitrogen, phosphorus, or silicon atoms in place of carbon atoms. Preferred cycloheteroalkyls have from 4-8 carbon atoms and heteroatoms in their ring structure, and more preferably have 4-6 carbons and heteroatoms in the ring structure. Cycloheteroalkyl groups may be substituted or unsubstituted. Unless the number of carbons is otherwise specified, “lower alkyl,” as used herein, means an alkyl group, as defined above, but having from one to ten carbons, more preferably from one to six carbon atoms in its backbone structure such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and tert-butyl. Likewise, “lower alkenyl” and “lower alkynyl” have similar chain lengths. Throughout the application, preferred alkyl groups are lower alkyls. In certain embodiments, a substituent designated herein as alkyl is a lower alkyl. “Alkenyl” refers to any cyclic or acyclic, branched or unbranched unsaturated carbon chain moiety having the number of carbon atoms specified, or up to 26 carbon atoms if no limitation on the number of carbon atoms is specified; and having one or more double bonds in the moiety. Alkenyl of 6 to 26 carbon atoms is exemplified by hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodenyl, tridecenyl, tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl, octadecenyl, nonadecenyl, eicosenyl, heneicosoenyl, docosenyl, tricosenyl, and tetracosenyl, in their various isomeric forms, where the unsaturated bond(s) can be located anywhere in the moiety and can have either the (Z) or the (E) configuration about the double bond(s). “Alkynyl” refers to hydrocarbyl moieties of the scope of alkenyl, but having one or more triple bonds in the moiety. The term “aryl” as used herein includes 3- to 12-membered substituted or unsubstituted single-ring aromatic groups in which each atom of the ring is carbon (i.e., carbocyclic aryl) or where one or more atoms are heteroatoms (i.e., heteroaryl). Preferably, aryl groups include 5- to 12-membered rings, more preferably 6- to 10-membered rings The term “aryl” also includes polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjoining rings wherein at least one of the rings is aromatic, e.g., the other cyclic rings can be cycloalkyls, cycloalkenyls, cycloalkynyls, aryls, heteroaryls, and / or heterocyclyls. Carboycyclic aryl groups include benzene, naphthalene, phenanthrene, phenol, aniline, and the like. Heteroaryl groups include substituted or unsubstituted aromatic 3- to 12-membered ring structures, more preferably 5- to 12-membered rings, more preferably 5- to 10-membered rings, whose ring structures include one to four heteroatoms. Heteroaryl groups include, for example, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine and pyrimidine, and the like. Aryl and heteroaryl can be monocyclic, bicyclic, or polycyclic. The term “halo”, “halide”, or “halogen” as used herein means halogen and includes, for example, and without being limited thereto, fluoro, chloro, bromo, iodo and the like, in both radioactive and non-radioactive forms. In a preferred embodiment, halo is selected from the group consisting of fluoro, chloro and bromo. The terms “heterocyclyl” or “heterocyclic group” or “heterocycloalkyl” refer to 3- to 12- membered ring structures, more preferably 5- to 12-membered rings, more preferably 5- to 10- membered rings, whose ring structures include one to four heteroatoms. Heterocycles can be monocyclic, bicyclic, spirocyclic, or polycyclic. Heterocyclyl groups include, for example, thiophene, thianthrene, furan, pyran, isobenzofuran, chromene, chromane, xanthene, phenoxathiin, pyrrole, imidazole, pyrazole, isothiazole, isoxazole, pyridine, pyrazine, pyrimidine, pyridazine, indolizine, isoindole, indole, indazole, purine, quinolizine, isoquinoline, quinoline, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, pteridine, carbazole, carboline, phenanthridine, acridine, pyrimidine, phenanthroline, phenazine, phenarsazine, phenothiazine, furazan, phenoxazine, pyrrolidine, oxolane, thiolane, oxazole, piperidine, piperazine, morpholine, lactones, lactams such as azetidinones and pyrrolidinones, sultams, sultones, and the like. The heterocyclic ring can be substituted at one or more positions with such substituents as described above, as for example, halogen, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, amino, nitro, sulfhydryl, imino, amido, phosphate, phosphonate, phosphinate, carbonyl, carboxyl, silyl, sulfamoyl, sulfinyl, ether, alkylthio, sulfonyl, ketone, aldehyde, ester, a heterocyclyl, an aromatic or heteroaromatic moiety, -CF3, -CN, and the like. The term “substituted” refers to moieties having substituents replacing a hydrogen on one or more carbons of the backbone. It will be understood that “substitution” or “substituted with” includes the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, e.g., which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. As used herein, the term “substituted” is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds. The permissible substituents can be one or more and the same or different for appropriate organic compounds. For purposes of this invention, the heteroatoms such as nitrogen may have hydrogen substituents and / or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms. Substituents can include any substituents described herein, for example, a halogen, a hydroxyl, a carbonyl (such as a carboxyl, an alkoxycarbonyl, a formyl, or an acyl), a thiocarbonyl (such as a thioester, a thioacetate, or a thioformate), an alkoxy, a phosphoryl, a phosphate, a phosphonate, a phosphinate, an amino, an amido, an amidine, an imine, a cyano, a nitro, an azido, a sulfhydryl, an alkylthio, a sulfate, a sulfonate, a sulfamoyl, a sulfonamido, a sulfonyl, a heterocyclyl, an aralkyl, or an aromatic or heteroaromatic moiety. In preferred embodiments, the substituents on substituted alkyls are selected from C1-6 alkyl, C3-6 cycloalkyl, halogen, carbonyl, cyano, or hydroxyl. In more preferred embodiments, the substituents on substituted alkyls are selected from fluoro, carbonyl, cyano, or hydroxyl. It will be understood by those skilled in the art that substituents can themselves be substituted, if appropriate. Unless specifically stated as “unsubstituted,” references to chemical moieties herein are understood to include substituted variants. For example, reference to an “aryl” group or moiety implicitly includes both substituted and unsubstituted variants. As used herein, the definition of each expression, e.g., alkyl, m, n, etc., when it occurs more than once in any structure, is intended to be independent of its definition elsewhere in the same structure. As used herein, “small molecules” refers to small organic or inorganic molecules of molecular weight below about 3,000 Daltons. In general, small molecules useful for the invention have a molecular weight of less than 3,000 Daltons (Da). The small molecules can be, e.g., from at least about 100 Da to about 3,000 Da (e.g., between about 100 to about 3,000 Da, about 100 to about 2500 Da, about 100 to about 2,000 Da, about 100 to about 1,750 Da, about 100 to about 1,500 Da, about 100 to about 1,250 Da, about 100 to about 1,000 Da, about 100 to about 750 Da, about 100 to about 500 Da, about 200 to about 1500, about 500 to about 1000, about 300 to about 1000 Da, or about 100 to about 250 Da). In some embodiments, a “small molecule” refers to an organic, inorganic, or organometallic compound typically having a molecular weight of less than about 1000. In some embodiments, a small molecule is an organic compound, with a size on the order of 1 nm. In some embodiments, small molecule drugs of the invention encompass oligopeptides and other biomolecules having a molecular weight of less than about 1000. An “effective amount” is an amount sufficient to effect beneficial or desired results. For example, a therapeutic amount is one that achieves the desired therapeutic effect. This amount can be the same or different from a prophylactically effective amount, which is an amount necessary to prevent onset of disease or disease symptoms. An effective amount can be administered in one or more administrations, applications or dosages. A therapeutically effective amount of a composition depends on the composition selected. The compositions can be administered from one or more times per day to one or more times per week; including once every other day. The skilled artisan will appreciate that certain factors may influence the dosage and timing required to effectively treat a subject, including but not limited to the severity of the disease or disorder, previous treatments, the general health and / or age of the subject, and other diseases present. Moreover, treatment of a subject with a therapeutically effective amount of the compositions described herein can include a single treatment or a series of treatments. The terms “decrease,” “reduce,” “reduced”, “reduction”, “decrease,” and “inhibit” are all used herein generally to mean a decrease by a statistically significant amount relative to a reference. However, for avoidance of doubt, “reduce,” “reduction” or “decrease” or “inhibit” typically means a decrease by at least 10% as compared to a reference level and can include, for example, a decrease by at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, up to and including, for example, the complete absence of the given entity or parameter ascompared to the reference level, or any decrease between 10-99% as compared to the absence of a given treatment. The terms “increased”, “increase” or “enhance” or “activate” are all used herein to generally mean an increase by a statically significant amount; for the avoidance of any doubt, the terms “increased”, “increase” or “enhance” or “activate” means an increase of at least 10% as compared to a reference level, for example an increase of at least about 20%, or at least about 30%, or at least about 40%, or at least about 50%, or at least about 60%, or at least about 70%, or at least about 80%, or at least about 90% or up to and including a 100% increase or any increase between 10-100% as compared to a reference level, or at least about a 2-fold, or at least about a 3-fold, or at least about a 4-fold, or at least about a 5-fold or at least about a 10- fold increase, or any increase between 2-fold and 10-fold or greater as compared to a reference level. As used herein, the term “modulate” includes up-regulation and down-regulation, e.g., enhancing or inhibiting a response. A “radiopharmaceutical agent,” as defined herein, refers to a pharmaceutical agent which contains at least one radiation-emitting radioisotope. Radiopharmaceutical agents are routinely used in nuclear medicine for the diagnosis and / or therapy of various diseases. The radiolabelled pharmaceutical agent, for example, a radiolabelled antibody, contains a radioisotope (RI) which serves as the radiation source. As contemplated herein, the term “radioisotope” includes metallic and non-metallic radioisotopes. The radioisotope is chosen based on the medical application of the radiolabeled pharmaceutical agents. When the radioisotope is a metallic radioisotope, a chelator is typically employed to bind the metallic radioisotope to the rest of the molecule. When the radioisotope is a non-metallic radioisotope, the non-metallic radioisotope is typically linked directly, or via a linker, to the rest of the molecule. For purposes of this invention, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 67th Ed., 1986-87, inside cover. Compounds of the Invention One aspect of the invention relates to a compound of Formula (I): or a pharmaceutically acceptable salt thereof, wherein: A is (C6-C10)aryl, 5- to 10-membered heteroaryl, (C3-C8)cycloalkyl, or 4- to 7-membered heterocycloalkyl; n is 0, 1, 2, 3, 4, or 5; R1is independently for each occurrence (C1-C6)alkyl, (C2-C6)alkynyl, (C2-C6)alkenyl, (C3- C8)cycloalkyl, (C3-C8)cycloalkoxy, (C6-C10)aryl, (C6-C10)aryloxy, (C6-C10)aryl(C1-C6)alkyl, 4- to 7-membered heterocycloalkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl, halo, cyano, amino, formyl, carboxy, or alkoxycarbonyl, wherein (C1-C6)alkyl, (C2-C6)alkynyl, (C2-C6)alkenyl, (C3-C8)cycloalkyl, C3- C8)cycloalkoxy, (C6-C10)aryl, (C6-C10)aryloxy, (C6-C10)aryl(C1-C6)alkyl, (C1-C6)alkoxy, (C1- C6)alkoxy(C1-C6)alkyl, and 4- to 7-membered heterocycloalkyl are each optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, 4- to 7-membered heterocycloalkyl, 5- to 6- membered heteroaryl, (C1-C6)alkoxy, (C1-C6)haloalkoxy, (C1-C6)fluoroalkoxy, 5- to 6-membered heteroaryloxy, or two vicinal occurrences of R1taken together with the atoms to which they are attached form a fused 5- to 7-membered cycloalkyl, 5- to 7-membered heterocycloalkyl ring, 5- to 6- membered heteroaryl ring or phenyl ring, any of which is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1- C6)alkyl, (C1-C6)haloalkyl (C3-C8)cycloalkyl, and (C1-C6)alkoxy; Q is N or CR2c; R2a, R2b, and R2c, are each independently hydrogen, halo, cyano, (C1-C6)alkyl, or (C3- C8)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; R3is (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C6)alkyl), (C6-C10)aryl, (C6- C10)aryl(C1-C6)alkyl), or 4- to 7-membered heterocycloalkyl; each of which is optionally substituted with one or more substituents independently selected from halo, cyano, (C1- C6)haloalkyl, hydroxy, (C1-C6)alkoxy(C1-C6)alkyl, and (C1-C6)alkoxy; X and Z are independently NR4, C(R5)2, or O; R4and R5independently for each occurrence hydrogen or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy, or when Z is NR4, R3and R4taken together with the nitrogen to which they are attached form a 4- to 7-member heterocycloalkyl optionally substituted with one or more (C1-C6)alkyl or halo; L is (C1-C6)alkylene optionally substituted with one or more substituents independently selected from halo, hydroxy, C1-C6)alkoxy, and cyano; W represents: –C(R6)2–C(R7)2–, –C(R7)2–, –O–C(R8)2–, –C(R8)2–O–, –C(R8)2–NR9–, –N=C(R10) –, or –O–; and R6, R7, R8, R9and R10are independently for each occurrence hydrogen, (C1-C6)alkyl,or NH2, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, cyano, hydroxy, (C1-C6)alkoxy(C1-C6)alkyl, and (C1-C6)alkoxy. In some embodiments of the compound of Formula (I), A is (C6-C10)aryl or 5- to 10-membered heteroaryl; n is 0, 1, 2, 3, 4, or 5; R1is independently for each occurrence (C1-C6)alkyl, (C3-C8)cycloalkyl, 4- to 7- membered heterocycloalkyl, (C1-C6)alkoxy, halo, cyano, formyl, carboxy, or alkoxycarbonyl, wherein (C1-C6)alkyl, (C3-C8)cycloalkyl, (C1-C6)alkoxy, and 4- to 7-membered heterocycloalkyl are each optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, and (C1-C6)alkoxy, or two vicinal occurrences of R1taken together with the atoms to which they are attached form a fused 5- to 7-membered cycloalkyl or 5- to 7-membered heterocycloalkyl ring, either of which is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, and (C1-C6)alkoxy; Q is N or CR2c; R2a, R2b, and R2c, are each independently hydrogen, halo, cyano, or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; R3is (C1-C6)alkyl optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; X and Z are independently NR4, C(R5)2, or O; R4and R5independently for each occurrence hydrogen or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; L is (C1-C6)alkylene optionally substituted with one or more substituents independently selected from halo, hydroxy, C1-C6)alkoxy, and cyano; W represents: –C(R6)2–C(R7)2–, –C(R7)2–, –O–C(R8)2–, –C(R8)2–O–, –C(R8)2–NR9–, –N=C(R10) –, or –O–; and R6, R7, R8, R9and R10are independently for each occurrence hydrogen or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy.: Another aspect of the invention relates to a compound Formula (II): or a pharmaceutically acceptable salt thereof, wherein A is (C6-C10)aryl, 5- to 10-membered heteroaryl, (C3-C8)cycloalkyl, or 4- to 7-membered heterocycloalkyl; n is 0, 1, 2, 3, 4, or 5; R1is independently for each occurrence (C1-C6)alkyl, (C2-C6)alkynyl, (C2-C6)alkenyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkoxy, (C6-C10)aryl, (C6-C10)aryloxy, (C6-C10)aryl(C1-C6)alkyl, 4- to 7-membered heterocycloalkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl, halo, cyano, amino, formyl, carboxy, or alkoxycarbonyl, wherein (C1-C6)alkyl, (C2-C6)alkynyl, (C2-C6)alkenyl, (C3-C8)cycloalkyl, C3- C8)cycloalkoxy, (C6-C10)aryl, (C6-C10)aryloxy, (C6-C10)aryl(C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl, and 4- to 7-membered heterocycloalkyl are each optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, 4- to 7-membered heterocycloalkyl, 5- to 6- membered heteroaryl, (C1-C6)alkoxy, (C1-C6)haloalkoxy, (C1-C6)fluoroalkoxy, 5- to 6-membered heteroaryloxy, or two vicinal occurrences of R1taken together with the atoms to which they are attached form a fused 5- to 7-membered cycloalkyl, 5- to 7-membered heterocycloalkyl ring, 5- to 6- membered heteroaryl ring or phenyl ring, any of which is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C1-C6)haloalkyl (C3-C8)cycloalkyl, and (C1-C6)alkoxy; Q is N or CR2c; R2a, R2b, and R2c, are each independently hydrogen, halo, cyano, (C1-C6)alkyl, or (C3- C8)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; R3is (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C6)alkyl), (C6-C10)aryl, (C6- C10)aryl(C1-C6)alkyl), or 4- to 7-membered heterocycloalkyl; each of which is optionally substituted with one or more substituents independently selected from halo, cyano, (C1-C6)haloalkyl, hydroxy, (C1-C6)alkoxy(C1-C6)alkyl, and (C1-C6)alkoxy; X and Z are independently NR4, C(R5)2, or O; R4and R5independently for each occurrence hydrogen or (C1-C6)alkyl, wherein (C1- C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy, or when Z is NR4, R3and R4taken together with the nitrogen to which they are attached form a 4- to 7-member heterocycloalkyl optionally substituted with one or more (C1-C6)alkyl or halo; L is (C1-C6)alkylene optionally substituted with one or more substituents independently selected from halo, hydroxy, C1-C6)alkoxy, and cyano; W represents: –C(R6)2–C(R7)2–, –C(R7)2–, –O–C(R8)2–, –C(R8)2–O–, –C(R8)2–NR9–, –N=C(R10) –, or –O–; and R6, R7, R8, R9and R10are independently for each occurrence hydrogen, (C1-C6)alkyl,or NH2, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, cyano, hydroxy, (C1-C6)alkoxy(C1-C6)alkyl, and (C1-C6)alkoxy. In other embodiments or of the compound of Formula (II), A is (C6-C10)aryl or 5- to 10-membered heteroaryl; n is 0, 1, 2, 3, 4 or 5; R1is independently for each occurrence (C1-C6)alkyl, (C3-C8)cycloalkyl, , 4- to 7- membered heterocycloalkyl, (C1-C6)alkoxy, halo, cyano, formyl, carboxy, or alkoxycarbonyl, wherein (C1-C6)alkyl, (C3-C8)cycloalkyl, 4- to 7-membered heterocycloalkyl, and (C1-C6)alkoxy are each optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, and (C1-C6)alkoxy; or two vicinal occurrences of R1taken together with the atoms to which they are attached form a fused 5- to 7-membered cycloalkyl or 5- to 7-membered heterocycloalkyl ring, either of which is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, and (C1-C6)alkoxy; Q is N or CR2c; R2a, R2b, and R2c, are each independently hydrogen, halo, cyano, or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; R3is (C1-C6)alkyl optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; X and Z are independently NR4, C(R5)2, or O; R4and R5are independently for each occurrence hydrogen or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; L is (C1-C6)alkylene optionally substituted with one or more substituents independently selected from halo, hydroxy, C1-C6)alkoxy, and cyano; Wa–Wbrepresents: –C(R6)2–C(R7)2–, –O–C(R8)2–, –C(R8)2–O–, –C(R8)2–NR9–, or –N=C(R10) –; and R6, R7, R8, R9and R10are independently for each occurrence hydrogen or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy. Yet another aspect of the invention relates to a compound of Formula (III): or a pharmaceutically acceptable salt thereof, A is (C6-C10)aryl, 5- to 10-membered heteroaryl, (C3-C8)cycloalkyl, or 4- to 7-membered heterocycloalkyl; n is 0, 1, 2, 3, 4, or 5; R1is independently for each occurrence (C1-C6)alkyl, (C2-C6)alkynyl, (C2-C6)alkenyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkoxy, (C6-C10)aryl, (C6-C10)aryloxy, (C6-C10)aryl(C1-C6)alkyl, 4- to 7-membered heterocycloalkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl, halo, cyano, amino, formyl, carboxy, or alkoxycarbonyl, wherein (C1-C6)alkyl, (C2-C6)alkynyl, (C2-C6)alkenyl, (C3-C8)cycloalkyl, C3- C8)cycloalkoxy, (C6-C10)aryl, (C6-C10)aryloxy, (C6-C10)aryl(C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl, and 4- to 7-membered heterocycloalkyl are each optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, 4- to 7-membered heterocycloalkyl, 5- to 6- membered heteroaryl, (C1-C6)alkoxy, (C1-C6)haloalkoxy, (C1-C6)fluoroalkoxy, 5- to 6-membered heteroaryloxy, or two vicinal occurrences of R1taken together with the atoms to which they are attached form a fused 5- to 7-membered cycloalkyl, 5- to 7-membered heterocycloalkyl ring, 5- to 6- membered heteroaryl ring or phenyl ring, any of which is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1- C6)alkyl, (C1-C6)haloalkyl (C3-C8)cycloalkyl, and (C1-C6)alkoxy; Q is N or CR2c; R2a, R2b, and R2c, are each independently hydrogen, halo, cyano, (C1-C6)alkyl, or (C3- C8)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; R3is (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C6)alkyl), (C6-C10)aryl, (C6- C10)aryl(C1-C6)alkyl), or 4- to 7-membered heterocycloalkyl; each of which is optionally substituted with one or more substituents independently selected from halo, cyano, (C1-C6)alkyl, (C1-C6)haloalkyl, hydroxy, (C1-C6)alkoxy(C1-C6)alkyl, and (C1-C6)alkoxy; X and Z are independently NR4, C(R5)2, or O; R4and R5independently for each occurrence hydrogen or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy, or when Z is NR4, R3and R4taken together with the nitrogen to which they are attached form a 4- to 7-member heterocycloalkyl optionally substituted with one or more (C1-C6)alkyl or halo, or when Z is C(R5)2, R3and one R5taken together with the carbon to which they are attached form a 4, (C3-C8)cycloalkyl optionally substituted with one or more (C1- C6)alkyl or halo; L is (C1-C6)alkylene optionally substituted with one or more substituents independently selected from halo, hydroxy, C1-C6)alkoxy, and cyano; R10is hydrogen, (C1-C6)alkyl,or NH2, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, cyano, hydroxy, (C1-C6)alkoxy(C1-C6)alkyl, and (C1-C6)alkoxy. In some embodiments of the conmpound of Formula (III), A is (C6-C10)aryl or 5- to 10-membered heteroaryl; n is 0, 1, 2, 3, 4 or 5; R1is independently for each occurrence (C1-C6)alkyl, (C3-C8)cycloalkyl, 4- to 7- membered heterocycloalkyl, (C1-C6)alkoxy, halo, cyano, formyl, carboxy, or alkoxycarbonyl, wherein (C1-C6)alkyl, (C3-C8)cycloalkyl, 4- to 7-membered heterocycloalkyl, and (C1-C6)alkoxy are each optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, and (C1-C6)alkoxy; or two vicinal occurrences of R1taken together with the atoms to which they are attached form a fused 5- to 7-membered cycloalkyl or 5- to 7-membered heterocycloalkyl ring, either of which is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, and (C1-C6)alkoxy; Q is N or CR2c; R2a, R2b, and R2c, are each independently hydrogen, halo, cyano, (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; R3is (C1-C6)alkyl optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; X and Z are independently NR4, C(R5)2, or O; R4and R5are independently for each occurrence hydrogen or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; L is (C1-C6)alkylene optionally substituted with one or more substituents independently selected from halo, hydroxy, C1-C6)alkoxy, and cyano; and R10is hydrogen or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy. In certain embodiments, A is phenyl. In certain embodiments, A is a 5- to 7-membered heteroaryl comprising 1 or 2 nitrogen atoms. In certain embodiments, A is pyridyl or diazolyl. thiazolyl, pyrazinyl, pyrimidinyl, while in other embodiments, A is pyridyl or diazolyl. In some embodiments, A is wherein A is isoquinolinyl or indazolyl. In other embodiments, A is cyclopentyl, cyclohexyl, or tetrahydropyranyl. In certain embodiments, R1is independently for each occurrence (C1-C6)alkyl, (C1- C6)alkoxy, fluoro, chloro, or cyano, wherein (C1-C6)alkyl and (C1-C6)alkoxy are optionally substituted with one or more substituents independently selected from fluoro and hydroxyl. In certain embodiments, at least one R1is fluoro, chloro, or cyano. In certain embodiments, at least one R1is (C1-C6)alkyl optionally substituted with one or more substituents independently selected from hydroxyl and fluoro. In certain preferred embodiments, R1is 2,2,2-trifluoroethyl-1-hydroxyethyl. In other preferred embodiments, at least one R1is difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluropropyl, or 4,4,4- trifluorobutyl. In certain embodiments, at least one R1is (C1-C6)alkoxy optionally substituted with at least one fluoro, preferably (C1-C3)alkoxy optionally substituted with at least one fluoro, more preferably difluoromethoxy or trifluoromethoxy. In other preferred embodiments, R1is methoxy or isopropoxy. In certain embodiments, R1is methyl optionally substituted with hydroxy or one or more fluoro. In certain embodiments, R1is (C1-C3)alkoxy optionally substituted with at least one fluoro. In certain embodiments, at least one R1is (C3-C8)cycloalkyl, preferably cyclopropyl or cyclobutyl. In certain embodiments, at least R1is (C3-C8)cycloalkoxy, preferably cyclopentyloxy, cyclohexyloxy. In certain embodiments, R1is (C2-C6)alkynyl optionally substituted with hydroxy. In certain embodiments, two vicinal occurrences of R1taken together with the atoms to which they are attached form a fused 5- to 7-membered cycloalkyl or 5- to 7-membered heterocycloalkyl ring, either of which is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3- C8)cycloalkyl, and (C1-C6)alkoxy. In certain embodiments, A is phenyl comprising two vicinal occurrences of R1, wherein the two vicinal occurrences of R1, taken together with the atoms to which they are attached, form a fused 5- to 7-membered cycloalkyl or 5- to 7-membered heterocycloalkyl ring. In certain embodiments, n is 2. In certain embodiments, n is 1. In certain embodiments, n is 0. In certain embodiments, Q is CR2c. In certain embodiments, Q is N. In certain embodiments, R2a, R2b, and R2care each hydrogen. In certain embodiments, at least one of R2a, R2b, and R2cis fluoro, chloro, or cyano. In certain embodiments, R3is (C1-C6)alkyl optionally substituted with hydroxy. In certain preferred embodiments, R3is t-butyl. In certain embodiments, R3is (C3-C8)cycloalkyl optionally substituted with one or more (C1-C6)alkyl, (C1-C6)fluoroalkyl, fluoro, or (C1-C6)alkoxy(C1-C6)alkyl. In more particular embodiments, the (C3-C8)cycloalkyl is cyclobutyl, cyclopentyl, cylohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl,bicycle[2.1.1]hexanyl, or bicyclo[3.1.0]hexanyl. Inb further particular embodiments, the (C3-C8)cycloalkyl is optionally substituted with one or more substituents selected from fluoro, trifluoromethyl, methoxymethyl, methyl, and hydroxyl. In certain embodiments, R3is 4- to 7-membered heterocycloalkyl optionally substituted with one or more substituents selected from (C1-C6)alkyl, (C1-C6)fluoroalkyl, or fluoro. In more particular embodiments, the 4- to 7-membered heterocycloalkyl is etrahydropyranyl or oxetanyl. In some embodiments, Z is NR4, R3and R4taken together with the nitrogen to which they are attached form a 4- to 7-member heterocycloalkyl optionally substituted with one or more (C1-C6)alkyl or halo. In some embodiments, the 4- to 7 membered heterocycloalkyl is azetidine or pyrrolidine, In certain embodiments, X is NR4or O. In certain embodiments, X is NH. In certain embodiments, Z is NR4, or O. In certain embodiments, Z is NH. In certain embodiments, one and only one of X and Z is CH2.In certain embodiments, X and Z are each NH. In certain embodiments, L is unsubstituted (C1-C6)alkylene. In certain embodiments, L is (C1-C6)alkylene substituted with hydroxy. In certain embodiments, L is (C1-C6)alkylene substituted with 1 to 3 halo atoms. In certain embodiments, L is –CH2–, –-CH(CH3)–, –CH(CH2CH3)–, or –CH(CH2OH)–. In certain embodiments, Wa–Wbrepresents: –C(R6)2–C(R7)2–. In certain embodiments, R6is (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy. In certain embodiments, at least one R7is (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, (C1- C6)alkoxy, and cyano. In certain embodiments, each R6and each R7is hydrogen. In certain embodiments, Wa–Wbrepresents: –O–C(R8)2–. In certain embodiments, R8is hydrogen. In certain embodiments, one R8(C1-C6)alkyl, preferably methyl; and one R8is hydrogen. In certain embodiments, Wa–Wbrepresents: –C(R8)2–O–, where each R8 is hydrogen. In certain embodiments, Wa–Wbrepresents: –C(R8)2–NR9–. In certain embodiments, each R8is hydrogen. In certain embodiments, R9is (C1-C6)alkyl, preferably methyl. In certain embodiments, Wa–Wbrepresents: –N=C(R10) –. In certain embodiments, R10is hydrogen. In certain embodiments, R10is (C1-C6)alkyl. In certain embodiments, R10is methyl. In certain embodiments, a compound is selected from Table 1: Table 1.

[0002] 258 259 260 261 262 263

[0003]

[0004] In certain embodiments, the compound is selected from Table 2. Table 2.

[0005] or a pharmaceutically acceptable salt thereof. In certain embodiments, the compounds are atropisomers. Additionally, unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds produced by the replacement of a hydrogen with deuterium or tritium, or of a carbon with a13C- or14C-enriched carbon are within the scope of this invention. Such compounds are useful, for example, as analytical tools, as probes in biological assays, or as therapeutic agents in accordance with the present invention. For example, in the case of variable R1, the (C1-C4)alkyl or the -O-(C1- C4)alkyl can be suitably deuterated (e.g., -CD3, -OCD3). Any compound of the invention can also be radiolabed for the preparation of a radiopharmaceutical agent. Methods of Treatment One aspect of the invention provides methods of inhibiting a thyroid stimulating hormone receptor, comnprising administering to a subject in need thereof a therapeutically effective amount of a compound described herein. Another aspect of the invention comprises treating or preventing a thyroid disease, comnprising administering to a subject in need thereof a therapeutically effective amount of a compound described herein. In certain embodiments, the subject has Graves' disease. In certain embodiments, the subject has Graves' ophthalmopathy. In certain embodiments, the subject has Graves' dermopathy. In certain embodiments, the subject has thyroid cancer. While not being bound by theory, TSHR in thyroid cells, and likely in fibroblasts and adipocytes in the supporting tissue behind the eye (in the retro-orbital space), also are stimulated by TSHR-stimulating antibodies (TSAbs), resulting in Graves' disease. Graves' disease, which is an autoimmune disease that occurs in 1% of the US population, has two important clinical components: 1) hyperthyroidism from stimulation of TSHR on thyroid cells and 2) Graves' orbitopathy (or Graves' ophthalmopathy or thyroid eye disease), which appears to result from stimulation of TSHR on retro-orbital fibroblasts and / or adipocytes. Hyperthyroidism, in particular Graves' hyperthyroidism, is a hypermetabolic state that affects virtually every tissue / cell in the body and can lead to, in particular, cardiovascular dysfunction and death. Graves' ophthalmopathy, also known as Graves' orbitopathy, occurs in 80% of Graves' hyperthyroid patients as diagnosed by computerized tomographic scan. Symptoms range from mild to moderate to severe to sight-threatening. Protrusion of the eyeball (proptosis) and varying degrees of extra-ocular muscle weakness or paralysis leading to double vision (diplopia) can be disfiguring and incapacitating. Graves dermopathy, also known as Pretibial myxedema, thyroid dermopathy, Jadassohn- Dössekker disease or Myxoedema tuberosum, is an infiltrative dermopathy, resulting as a complication of Graves' disease, with an incidence rate of about 1-5% in patients. The disease usually presents itself as a waxy, discolored induration of the skin on the anterior aspect of the lower legs. In certain embodiments, a disease that can be treated o prevented by TSHR antagonists is thyroid cancer.While not being bound by theory, TSHR is expressed in thyroid cancer cells and regulates the growth, proliferation and metastatic potential of thyroid cancer cells. The thyroid gland is, as is well known, one site of metabolic control within the body. Cancer of the thyroid gland is not particularly common, but the high rate of disease re- occurrence necessitates long-term surveillance. Usually, during treatment for cancer of the thyroid, the majority of the thyroid tumor is removed, but a small amount often remains that must be treated by radioactive iodide therapy. Indeed, thyroid cancer is characterized by a high likelihood of relapses in up to 30% of patients, even after successful therapy. In rare cases, the TSHR contains a hereditary mutation that makes it more active than the normal TSHR, resulting in hereditary non-immune hyperthyroidism. TSHR antagonists could be effective treatment for these patients also. A “TSHR antagonist” as described herein blocks or inhibits the action of the agonists (TSH or thyroid-stimulating antibodies for TSHR. Small-molecule ligands for the TSHR (antagonists) typically bind to an intra-membrane domain of the receptor, and act by inducing a conformational change rather than simply competing for TSH binding to its extracellular site on the receptor. In certain embodiments, the antagonists may be selective antagonists for TSHR (i.e, the compounds do not activate or modulate other hormone receptors, particularly luteinizing hormone / chorionic gonadotropin receptor (LHCGR) and follicle-stimulating hormone receptor (FSHR)). In certain embodiments, the antagonists disclosed herein may be used for treating hyperthyroidism in a subject. For example, the antagonists may inhibit mutant TSHRs with higher than normal basal signaling activities (CAMs) that cause an unusual form of hyperthyroidism. In another example, the antagonists may inhibit stimulation by antibodies found in Graves' disease, which is the most common form of hyperthyroidism. In certain embodiments, the TSHR antagonists are useful for treating TSHR-mediated thyroid cancer or hyperthyroidism by blocking TSHR-stimulating antibodies (TSAbs) in Graves' hyperthyroidism. In certain embodiments, the compound is administered orally to the subject. In certain embodiments, the compound is administered parenterally to the subject. In certain embodiments, the disease is prevented. In other embodiments, the disease is treated. Pharmaceutical Compositions, Routes of Administration, and Dosing In certain embodiments, the invention is directed to a pharmaceutical composition, comprising a compound of the invention, e.g. a compound of Formula (1), and a pharmaceutically acceptable carrier. In certain embodiments, the invention is directed to a pharmaceutical composition, comprising a compound of any of the disclosed embodiments, and a pharmaceutically acceptable carrier. In certain embodiments, the invention is directed to a pharmaceutical composition, comprising a compound of Table 1 or 2, and a pharmaceutically acceptable carrier. In certain embodiments, the pharmaceutical composition comprises a plurality of compounds of the invention and a pharmaceutically acceptable carrier. In certain embodiments, a pharmaceutical composition of the invention further comprises at least one additional pharmaceutically active agent other than a compound of the invention. The at least one additional pharmaceutically active agent can be an agent useful in the treatment of ischemia-reperfusion injury. Pharmaceutical compositions of the invention can be prepared by combining one or more compounds of the invention with a pharmaceutically acceptable carrier and, optionally, one or more additional pharmaceutically active agents. As stated above, an “effective amount” refers to any amount that is sufficient to achieve a desired biological effect. Combined with the teachings provided herein, by choosing among the various active compounds and weighing factors such as potency, relative bioavailability, patient body weight, severity of adverse side-effects and mode of administration, an effective prophylactic or therapeutic treatment regimen can be planned which does not cause substantial unwanted toxicity and yet is effective to treat the particular subject. The effective amount for any particular application can vary depending on such factors as the disease or condition being treated, the particular compound of the invention being administered, the size of the subject, or the severity of the disease or condition. One of ordinary skill in the art can empirically determine the effective amount of a particular compound of the invention and / or other therapeutic agent without necessitating undue experimentation. A maximum dose may be used, that is, the highest safe dose according to some medical judgment. Multiple doses per day may be contemplated to achieve appropriate systemic levels of compounds. Appropriate systemic levels can be determined by, for example, measurement of the patient’s peak or sustained plasma level of the drug. “Dose” and “dosage” are used interchangeably herein. In certain embodiments, intravenous administration of a compound may typically be from 0.1 mg / kg / day to 20 mg / kg / day. In one embodiment, intravenous administration of a compound may typically be from 0.1 mg / kg / day to 2 mg / kg / day. In one embodiment, intravenous administration of a compound may typically be from 0.5 mg / kg / day to 5 mg / kg / day. In one embodiment, intravenous administration of a compound may typically be from 1 mg / kg / day to 20 mg / kg / day. In one embodiment, intravenous administration of a compound may typically be from 1 mg / kg / day to 10 mg / kg / day. Generally, daily oral doses of a compound will be, for human subjects, from about 0.01 milligrams / kg per day to 1000 milligrams / kg per day. It is expected that oral doses in the range of 0.5 to 50 milligrams / kg, in one or more administrations per day, will yield therapeutic results. Dosage may be adjusted appropriately to achieve desired drug levels, local or systemic, depending upon the mode of administration. For example, it is expected that intravenous administration would be from one order to several orders of magnitude lower dose per day. In the event that the response in a subject is insufficient at such doses, even higher doses (or effective higher doses by a different, more localized delivery route) may be employed to the extent that patient tolerance permits. Multiple doses per day are contemplated to achieve appropriate systemic levels of the compound. For any compound described herein the therapeutically effective amount can be initially determined from animal models. A therapeutically effective dose can also be determined from human data for compounds which have been tested in humans and for compounds which are known to exhibit similar pharmacological activities, such as other related active agents. Higher doses may be required for parenteral administration. The applied dose can be adjusted based on the relative bioavailability and potency of the administered compound. Adjusting the dose to achieve maximal efficacy based on the methods described above and other methods as are well- known in the art is well within the capabilities of the ordinarily skilled artisan. The formulations of the invention can be administered in pharmaceutically acceptable solutions, which may routinely contain pharmaceutically acceptable concentrations of salt, buffering agents, preservatives, compatible carriers, adjuvants, and optionally other therapeutic ingredients. For use in therapy, an effective amount of the compound can be administered to a subject by any mode that delivers the compound to the desired surface. Administering a pharmaceutical composition may be accomplished by any means known to the skilled artisan. Routes of administration include but are not limited to intravenous, intramuscular, intraperitoneal, intravesical (urinary bladder), oral, subcutaneous, direct injection (for example, into a tumor or abscess), mucosal (e.g., topical to eye), inhalation, and topical. For intravenous and other parenteral routes of administration, a compound of the invention can be formulated as a lyophilized preparation, as a lyophilized preparation of liposome-intercalated or -encapsulated active compound, as a lipid complex in aqueous suspension, or as a salt complex. Lyophilized formulations are generally reconstituted in suitable aqueous solution, e.g., in sterile water or saline, shortly prior to administration. For oral administration, the compounds can be formulated readily by combining the active compound(s) with pharmaceutically acceptable carriers well known in the art. Such carriers enable the compounds of the invention to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions and the like, for oral ingestion by a subject to be treated. Pharmaceutical preparations for oral use can be obtained as solid excipient, optionally grinding a resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries, if desired, to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and / or polyvinylpyrrolidone (PVP). If desired, disintegrating agents may be added, such as the cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate. Optionally the oral formulations may also be formulated in saline or buffers, e.g., EDTA for neutralizing internal acid conditions or may be administered without any carriers. Also specifically contemplated are oral dosage forms of the above component or components. The component or components may be chemically modified so that oral delivery of the derivative is efficacious. Generally, the chemical modification contemplated is the attachment of at least one moiety to the component molecule itself, where said moiety permits (a) inhibition of acid hydrolysis; and (b) uptake into the blood stream from the stomach or intestine. Also desired is the increase in overall stability of the component or components and increase in circulation time in the body. Examples of such moieties include: polyethylene glycol, copolymers of ethylene glycol and propylene glycol, carboxymethyl cellulose, dextran, polyvinyl alcohol, polyvinyl pyrrolidone and polyproline. Abuchowski and Davis, “Soluble Polymer- Enzyme Adducts”, In: Enzymes as Drugs, Hocenberg and Roberts, eds., Wiley-Interscience, New York, N.Y., pp.367-383 (1981); Newmark et al., J Appl Biochem 4:185-9 (1982). Other polymers that could be used are poly-1,3-dioxolane and poly-1,3,6-tioxocane. For pharmaceutical usage, as indicated above, polyethylene glycol moieties are suitable. For the component (or derivative) the location of release may be the stomach, the small intestine (the duodenum, the jejunum, or the ileum), or the large intestine. One skilled in the art has available formulations which will not dissolve in the stomach, yet will release the material in the duodenum or elsewhere in the intestine. Preferably, the release will avoid the deleterious effects of the stomach environment, either by protection of the compound of the invention (or derivative) or by release of the biologically active material beyond the stomach environment, such as in the intestine. To ensure full gastric resistance a coating impermeable to at least pH 5.0 is essential. Examples of the more common inert ingredients that are used as enteric coatings are cellulose acetate trimellitate (CAT), hydroxypropylmethylcellulose phthalate (HPMCP), HPMCP 50, HPMCP 55, polyvinyl acetate phthalate (PVAP), Eudragit L30D, Aquateric, cellulose acetate phthalate (CAP), Eudragit L, Eudragit S, and shellac. These coatings may be used as mixed films. A coating or mixture of coatings can also be used on tablets, which are not intended for protection against the stomach. This can include sugar coatings, or coatings which make the tablet easier to swallow. Capsules may consist of a hard shell (such as gelatin) for delivery of dry therapeutic (e.g., powder); for liquid forms, a soft gelatin shell may be used. The shell material of cachets could be thick starch or other edible paper. For pills, lozenges, molded tablets or tablet triturates, moist massing techniques can be used. The therapeutic can be included in the formulation as fine multi-particulates in the form of granules or pellets of particle size about 1 mm. The formulation of the material for capsule administration could also be as a powder, lightly compressed plugs or even as tablets. The therapeutic could be prepared by compression. Colorants and flavoring agents may all be included. For example, the compound of the invention (or derivative) may be formulated (such as by liposome or microsphere encapsulation) and then further contained within an edible product, such as a refrigerated beverage containing colorants and flavoring agents. One may dilute or increase the volume of the therapeutic with an inert material. These diluents could include carbohydrates, especially mannitol, α-lactose, anhydrous lactose, cellulose, sucrose, modified dextrans and starch. Certain inorganic salts may also be used as fillers including calcium triphosphate, magnesium carbonate and sodium chloride. Some commercially available diluents are Fast-Flo, Emdex, STA-Rx 1500, Emcompress and Avicell. Disintegrants may be included in the formulation of the therapeutic into a solid dosage form. Materials used as disintegrates include but are not limited to starch, including the commercial disintegrant based on starch, Explotab. Sodium starch glycolate, Amberlite, sodium carboxymethylcellulose, ultramylopectin, sodium alginate, gelatin, orange peel, acid carboxymethyl cellulose, natural sponge and bentonite may all be used. Another form of the disintegrants are the insoluble cationic exchange resins. Powdered gums may be used as disintegrants and as binders and these can include powdered gums such as agar, Karaya or tragacanth. Alginic acid and its sodium salt are also useful as disintegrants. Binders may be used to hold the therapeutic agent together to form a hard tablet and include materials from natural products such as acacia, tragacanth, starch and gelatin. Others include methyl cellulose (MC), ethyl cellulose (EC) and carboxymethyl cellulose (CMC). Polyvinyl pyrrolidone (PVP) and hydroxypropylmethyl cellulose (HPMC) could both be used in alcoholic solutions to granulate the therapeutic. An anti-frictional agent may be included in the formulation of the therapeutic to prevent sticking during the formulation process. Lubricants may be used as a layer between the therapeutic and the die wall, and these can include but are not limited to; stearic acid including its magnesium and calcium salts, polytetrafluoroethylene (PTFE), liquid paraffin, vegetable oils and waxes. Soluble lubricants may also be used such as sodium lauryl sulfate, magnesium lauryl sulfate, polyethylene glycol of various molecular weights, Carbowax 4000 and 6000. Glidants that might improve the flow properties of the drug during formulation and to aid rearrangement during compression might be added. The glidants may include starch, talc, pyrogenic silica and hydrated silicoaluminate. To aid dissolution of the therapeutic into the aqueous environment a surfactant might be added as a wetting agent. Surfactants may include anionic detergents such as sodium lauryl sulfate, dioctyl sodium sulfosuccinate and dioctyl sodium sulfonate. Cationic detergents which can be used and can include benzalkonium chloride and benzethonium chloride. Potential non- ionic detergents that could be included in the formulation as surfactants include lauromacrogol 400, polyoxyl 40 stearate, polyoxyethylene hydrogenated castor oil 10, 50 and 60, glycerol monostearate, polysorbate 40, 60, 65 and 80, sucrose fatty acid ester, methyl cellulose and carboxymethyl cellulose. These surfactants could be present in the formulation of the compound of the invention or derivative either alone or as a mixture in different ratios. Pharmaceutical preparations which can be used orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules can contain the active ingredients in admixture with filler such as lactose, binders such as starches, and / or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers may be added. Microspheres formulated for oral administration may also be used. Such microspheres have been well defined in the art. All formulations for oral administration should be in dosages suitable for such administration. For buccal administration, the compositions may take the form of tablets or lozenges formulated in conventional manner. For topical administration, the compound may be formulated as solutions, gels, ointments, creams, suspensions, etc. as are well-known in the art. Systemic formulations include those designed for administration by injection, e.g., subcutaneous, intravenous, intramuscular, intrathecal or intraperitoneal injection, as well as those designed for transdermal, transmucosal oral or pulmonary administration. For administration by inhalation, compounds for use according to the present invention may be conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebulizer, with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of e.g., gelatin for use in an inhaler or insufflator may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch. Also contemplated herein is pulmonary delivery of the compounds disclosed herein (or salts thereof). The compound is delivered to the lungs of a mammal while inhaling and traverses across the lung epithelial lining to the blood stream. Other reports of inhaled molecules include Adjei et al., Pharm Res 7:565-569 (1990); Adjei et al., Int J Pharmaceutics 63:135-144 (1990) (leuprolide acetate); Braquet et al., J Cardiovasc Pharmacol 13(suppl.5):143-146 (1989) (endothelin-1); Hubbard et al., Annal Int Med 3:206-212 (1989) (α1-antitrypsin); Smith et al., 1989, J Clin Invest 84:1145-1146 (a-1-proteinase); Oswein et al., 1990, "Aerosolization of Proteins", Proceedings of Symposium on Respiratory Drug Delivery II, Keystone, Colorado, March, (recombinant human growth hormone); Debs et al., 1988, J Immunol 140:3482-3488 (interferon-gamma and tumor necrosis factor alpha) and Platz et al., U.S. Pat. No. 5,284,656 (granulocyte colony stimulating factor; incorporated by reference). A method and composition for pulmonary delivery of drugs for systemic effect is described in U.S. Pat. No.5,451,569 (incorporated by reference), issued Sep. 19, 1995 to Wong et al. Contemplated for use in the practice of this invention are mechanical devices designed for pulmonary delivery of therapeutic products, including but not limited to nebulizers, metered dose inhalers, and powder inhalers, all of which are familiar to those skilled in the art. Some specific examples of commercially available devices suitable for the practice of this invention are the Ultravent nebulizer, manufactured by Mallinckrodt, Inc., St. Louis, Mo.; the Acorn II nebulizer, manufactured by Marquest Medical Products, Englewood, Colo.; the Ventolin metered dose inhaler, manufactured by Glaxo Inc., Research Triangle Park, North Carolina; and the Spinhaler powder inhaler, manufactured by Fisons Corp., Bedford, Mass. All such devices require the use of formulations suitable for the dispensing of the compounds of the invention. Typically, each formulation is specific to the type of device employed and may involve the use of an appropriate propellant material, in addition to the usual diluents, adjuvants and / or carriers useful in therapy. Also, the use of liposomes, microcapsules or microspheres, inclusion complexes, or other types of carriers is contemplated. Chemically modified compound of the invention may also be prepared in different formulations depending on the type of chemical modification or the type of device employed. Formulations suitable for use with a nebulizer, either jet or ultrasonic, will typically comprise a compound of the invention (or derivative) dissolved in water at a concentration of about 0.1 to 25 mg of biologically active compound of the invention per mL of solution. The formulation may also include a buffer and a simple sugar (e.g., for inhibitor stabilization and regulation of osmotic pressure). The nebulizer formulation may also contain a surfactant, to reduce or prevent surface induced aggregation of the compound of the invention caused by atomization of the solution in forming the aerosol. Formulations for use with a metered-dose inhaler device will generally comprise a finely divided powder containing the compound of the invention (or derivative) suspended in a propellant with the aid of a surfactant. The propellant may be any conventional material employed for this purpose, such as a chlorofluorocarbon, a hydrochlorofluorocarbon, a hydrofluorocarbon, or a hydrocarbon, including trichlorofluoromethane, dichlorodifluoromethane, dichlorotetrafluoroethanol, and 1,1,1,2-tetrafluoroethane, or combinations thereof. Suitable surfactants include sorbitan trioleate and soya lecithin. Oleic acid may also be useful as a surfactant. Formulations for dispensing from a powder inhaler device will comprise a finely divided dry powder containing a compound of the invention (or derivative) and may also include a bulking agent, such as lactose, sorbitol, sucrose, or mannitol in amounts which facilitate dispersal of the powder from the device, e.g., 50 to 90% by weight of the formulation. The compound of the invention (or derivative) should advantageously be prepared in particulate form with an average particle size of less than 10 micrometers (μm), most preferably 0.5 to 5 μm, for most effective delivery to the deep lung. Nasal delivery of a pharmaceutical composition of the present invention is also contemplated. Nasal delivery allows the passage of a pharmaceutical composition of the present invention to the blood stream directly after administering the therapeutic product to the nose, without the necessity for deposition of the product in the lung. Formulations for nasal delivery include those with dextran or cyclodextran. For nasal administration, a useful device is a small, hard bottle to which a metered dose sprayer is attached. In one embodiment, the metered dose is delivered by drawing the pharmaceutical composition of the present invention solution into a chamber of defined volume, which chamber has an aperture dimensioned to aerosolize and aerosol formulation by forming a spray when a liquid in the chamber is compressed. The chamber is compressed to administer the pharmaceutical composition of the present invention. In a specific embodiment, the chamber is a piston arrangement. Such devices are commercially available. Alternatively, a plastic squeeze bottle with an aperture or opening dimensioned to aerosolize an aerosol formulation by forming a spray when squeezed is used. The opening is usually found in the top of the bottle, and the top is generally tapered to partially fit in the nasal passages for efficient administration of the aerosol formulation. Preferably, the nasal inhaler will provide a metered amount of the aerosol formulation, for administration of a measured dose of the drug. The compounds, when it is desirable to deliver them systemically, may be formulated for parenteral administration by injection, e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multi- dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and / or dispersing agents. Pharmaceutical formulations for parenteral administration include aqueous solutions of the active compounds in water-soluble form. Additionally, suspensions of the active compounds may be prepared as appropriate oily injection suspensions. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides, or liposomes. Aqueous injection suspensions may contain substances which increase the viscosity of the suspension, such as sodium carboxymethylcellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility of the compounds to allow for the preparation of highly concentrated solutions. Alternatively, the active compounds may be in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use. The compounds may also be formulated in rectal or vaginal compositions such as suppositories or retention enemas, e.g., containing conventional suppository bases such as cocoa butter or other glycerides. In addition to the formulations described above, a compound may also be formulated as a depot preparation. Such long acting formulations may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt. The pharmaceutical compositions also may comprise suitable solid or gel phase carriers or excipients. Examples of such carriers or excipients include but are not limited to calcium carbonate, calcium phosphate, various sugars, starches, cellulose derivatives, gelatin, and polymers such as polyethylene glycols. Suitable liquid or solid pharmaceutical preparation forms are, for example, aqueous or saline solutions for inhalation, microencapsulated, encochleated, coated onto microscopic gold particles, contained in liposomes, nebulized, aerosols, pellets for implantation into the skin, or dried onto a sharp object to be scratched into the skin. The pharmaceutical compositions also include granules, powders, tablets, coated tablets, (micro)capsules, suppositories, syrups, emulsions, suspensions, creams, drops or preparations with protracted release of active compounds, in whose preparation excipients and additives and / or auxiliaries such as disintegrants, binders, coating agents, swelling agents, lubricants, flavorings, sweeteners or solubilizers are customarily used as described above. The pharmaceutical compositions are suitable for use in a variety of drug delivery systems. For a brief review of methods for drug delivery, see Langer R, Science 249:1527-33 (1990). The compound of the invention and optionally other therapeutics may be administered per se (neat) or in the form of a pharmaceutically acceptable salt or cocrystal. When used in medicine the salts or cocrystals should be pharmaceutically acceptable, but non-pharmaceutically acceptable salts or cocrystals may conveniently be used to prepare pharmaceutically acceptable salts or cocrystals thereof. Such salts include, but are not limited to, those prepared from the following acids: hydrochloric, hydrobromic, sulphuric, nitric, phosphoric, maleic, acetic, salicylic, p-toluene sulphonic, tartaric, citric, methane sulphonic, formic, malonic, succinic, naphthalene-2-sulphonic, and benzene sulphonic. Also, such salts can be prepared as alkaline metal or alkaline earth salts, such as sodium, potassium or calcium salts of the carboxylic acid group. Suitable buffering agents include: acetic acid and a salt (1-2% w / v); citric acid and a salt (1-3% w / v); boric acid and a salt (0.5-2.5% w / v); and phosphoric acid and a salt (0.8-2% w / v). Suitable preservatives include benzalkonium chloride (0.003-0.03% w / v); chlorobutanol (0.3- 0.9% w / v); parabens (0.01-0.25% w / v) and thimerosal (0.004-0.02% w / v). Pharmaceutical compositions of the invention contain an effective amount of a compound as described herein and optionally therapeutic agents included in a pharmaceutically acceptable carrier. The term “pharmaceutically acceptable carrier” means one or more compatible solid or liquid filler, diluents or encapsulating substances which are suitable for administration to a human or other vertebrate animal. The term “carrier” denotes an organic or inorganic ingredient, natural or synthetic, with which the active ingredient is combined to facilitate the application. The components of the pharmaceutical compositions also are capable of being commingled with the compounds of the present invention, and with each other, in a manner such that there is no interaction which would substantially impair the desired pharmaceutical efficiency. The therapeutic agent(s), including specifically but not limited to a compound of the invention, may be provided in particles. Particles as used herein means nanoparticles or microparticles (or in some instances larger particles) which can consist in whole or in part of the compound of the invention or the other therapeutic agent(s) as described herein. The particles may contain the therapeutic agent(s) in a core surrounded by a coating, including, but not limited to, an enteric coating. The therapeutic agent(s) also may be dispersed throughout the particles. The therapeutic agent(s) also may be adsorbed into the particles. The particles may be of any order release kinetics, including zero-order release, first-order release, second-order release, delayed release, sustained release, immediate release, and any combination thereof, etc. The particle may include, in addition to the therapeutic agent(s), any of those materials routinely used in the art of pharmacy and medicine, including, but not limited to, erodible, nonerodible, biodegradable, or nonbiodegradable material or combinations thereof. The particles may be microcapsules which contain the compound of the invention in a solution or in a semi-solid state. The particles may be of virtually any shape. Both non-biodegradable and biodegradable polymeric materials can be used in the manufacture of particles for delivering the therapeutic agent(s). Such polymers may be natural or synthetic polymers. The polymer is selected based on the period of time over which release is desired. Bioadhesive polymers of particular interest include bioerodible hydrogels described in Sawhney H S et al. (1993) Macromolecules 26:581-7, the teachings of which are incorporated herein. These include polyhyaluronic acids, casein, gelatin, glutin, polyanhydrides, polyacrylic acid, alginate, chitosan, poly(methyl methacrylates), poly(ethyl methacrylates), poly(butylmethacrylate), poly(isobutyl methacrylate), poly(hexylmethacrylate), poly(isodecyl methacrylate), poly(lauryl methacrylate), poly(phenyl methacrylate), poly(methyl acrylate), poly(isopropyl acrylate), poly(isobutyl acrylate), and poly(octadecyl acrylate). The therapeutic agent(s) may be contained in controlled release systems. The term “controlled release” is intended to refer to any drug-containing formulation in which the manner and profile of drug release from the formulation are controlled. This refers to immediate as well as non-immediate release formulations, with non-immediate release formulations including but not limited to sustained release and delayed release formulations. The term “sustained release” (also referred to as “extended release”) is used in its conventional sense to refer to a drug formulation that provides for gradual release of a drug over an extended period of time, and that preferably, although not necessarily, results in substantially constant blood levels of a drug over an extended time period. The term “delayed release” is used in its conventional sense to refer to a drug formulation in which there is a time delay between administration of the formulation and the release of the drug there from. “Delayed release” may or may not involve gradual release of drug over an extended period of time, and thus may or may not be “sustained release.” Use of a long-term sustained release implant may be particularly suitable for treatment of chronic conditions. “Long-term” release, as used herein, means that the implant is constructed and arranged to deliver therapeutic levels of the active ingredient for at least 7 days, and preferably 30-60 days. Long-term sustained release implants are well-known to those of ordinary skill in the art and include some of the release systems described above. It will be understood by one of ordinary skill in the relevant arts that other suitable modifications and adaptations to the compositions and methods described herein are readily apparent from the description of the invention contained herein in view of information known to the ordinarily skilled artisan, and may be made without departing from the scope of the invention or any embodiment thereof. Having now described the present invention in detail, the same will be more clearly understood by reference to the following examples, which are included herewith for purposes of illustration only and are not intended to be limiting of the invention. EXAMPLES The invention is further described in the following examples, which do not limit the scope of the invention described in the claims. Example 1: 1-(1-benzyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(tert-butyl)urea Synthetic Scheme 1-benzyl-6-nitro-3,4-dihydroquinolin-2(1H)-one To a solution of 6-nitro-3,4-dihydroquinolin-2(1H)-one (1 g, 5.204 mmol, 1 equiv) in DMF (20 mL) was added K2CO3 (2.154 g, 15.611 mmol, 3 equiv) and (bromomethyl)benzene (979 mg, 5.724 mmol, 1.1 equiv). The resulting mixture was stirred for 16 h at rt. The mixture was diuted with EtOAc (100 mL), washed with water (3 x 50 mL), brine (2 x 50 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 1-benzyl-6-nitro-3,4-dihydroquinolin-2(1H)-one (500 mg, 34.04%) as a white solid. 6-amino-1-benzyl-3,4-dihydroquinolin-2(1H)-one To a solution of 1-benzyl-6-nitro-3,4-dihydroquinolin-2(1H)-one (0.45 g, 1.590 mmol, 1 equiv) in EtOH (10 mL) and H2O (2.5 mL) was added Fe (888.0 mg, 15.90 mmol, 10 equiv) and NH4Cl (850.5 mg, 15.90 mmol, 10 equiv).The resulting mixture was stirred for 2 h at 60 °C and stirred until the starting material was totally consumed by TLC. The reaction mixture was quenched by water and extracted with EA (3 x 30 mL).The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) to afford 6- amino-1-benzyl-3,4-dihydroquinolin-2(1H)-one (350 mg, 87.28%) as a yellow solid. MS (ESI): mass calcd. for C16H16N2O: 252.13 m / z, found 253.10 [M+H]+. 1-(1-benzyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(tert-butyl)urea To a solution of 6-amino-1-benzyl-3,4-dihydroquinolin-2(1H)-one (150 mg, 0.594 mmol, 1 equiv) in DCM (8 mL) was added TEA (179.9 mg, 1.782 mmol, 3 equiv) and 2-isocyanato-2- methylpropane (176.65 mg, 1.782 mmol, 3 equiv). The resulting mixture was stirred for 16 h at rt. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column eluted with PE / EA (2:1) & Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 28% B to 53% B in 9 min, 53% B; Wave Length: 254 / 220 nm; RT1(min): 8.52; Number Of Runs: 0) to afford 1-(1-benzyl-2-oxo-1,2,3,4-tetrahydroquinolin-6- yl)-3-(tert-butyl)urea (60.2 mg, 28.94%) as an off-white solid. MS (ESI): mass calcd. For C21H25N3O2, 351.19 m / z, found 352.20 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.08 (s, 1H), 7.26 – 7.34 (m, 3H), 7.16 – 7.25 (m, 3H), 6.95 (dd, J = 8.8, 2.5 Hz, 1H), 6.76 (d, J = 8.8 Hz, 1H), 5.90 (s, 1H), 5.09 (s, 2H), 2.87 (dd, J = 8.7, 5.9 Hz, 2H), 2.64 (dd, J = 8.7, 5.9 Hz, 2H), 1.26 (s, 9H). Example 2: 1-(tert-butyl)-3-(2-oxo-1-(pyridin-2-ylmethyl)-1,2,3,4-tetrahydroquinolin-6- yl)urea 6-nitro-1-(pyridin-2-ylmethyl)-3,4-dihydroquinolin-2(1H)-one To a solution of 6-nitro-3,4-dihydro-1H-quinolin-2-one (500 mg, 2.602 mmol, 1 equiv) in DMF (10 mL) was added K2CO3 (1078.7 mg, 7.805 mmol, 3 equiv) and 2- (bromomethyl)pyridine (492.3 mg, 2.862 mmol, 1 equiv). The resulting mixture was stirred for 16 h at rt. The mixture was diuted with EtOAc (100 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 6-nitro-1-(pyridin-2-ylmethyl)-3,4- dihydroquinolin-2(1H)-one (500 mg, 63.20%) as a white solid. MS (ESI): mass calcd. for C15H13N3O3283.10 m / z, found 284.05 [M+H]+. 6-amino-1-(pyridin-2-ylmethyl)-3,4-dihydroquinolin-2-one To a solution of 6-nitro-1-(pyridin-2-ylmethyl)-3,4-dihydroquinolin-2-one (440 mg, 1.553 mmol, 1 equiv) in EtOH (10 mL) and H2O (2.5 mL) was added Fe (867.3 mg, 15.532 mmol, 10 equiv) and NH4Cl (830.8 mg, 15.530 mmol, 10 equiv). The resulting mixture was stirred for 2 h at 60 °C. The reaction mixture was quenched by water and extracted with EA (3 x 30 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) to afford 6-amino-1-(pyridin-2-ylmethyl)-3,4- dihydroquinolin-2-one (200 mg, 46.52%) as a yellow solid. MS (ESI): mass calcd. for C15H15N3O, 253.12 m / z, found 254.15 [M+H]+. 1-(tert-butyl)-3-(2-oxo-1-(pyridin-2-ylmethyl)-1,2,3,4-tetrahydroquinolin-6-yl)urea To a solution of 6-amino-1-(pyridin-2-ylmethyl)-3,4-dihydroquinolin-2(1H)-one (200 mg, 0.793 mmol, 1 equiv) in DCM (5 mL) was added 2-isocyanato-2-methylpropane (234.8 mg, 2.369 mmol, 3 equiv) and TEA (79.9 mg, 0.790 mmol, 1 equiv). The resulting mixture was stirred for overnight at rt. The reaction mixture was quenched by water and extracted with EA (3 x 30 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) to afford & Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water (10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 22% B to 34% B in 10.5 min; Wave Length: 254 / 220 nm; RT1(min): 11.3; Number Of Runs: 4) to afford 1-(tert-butyl)-3-(2-oxo-1-(pyridin-2- ylmethyl)-1,2,3,4-tetrahydroquinolin-6-yl)urea (83.1 mg, 29.82%) as a white solid. MS (ESI): mass calcd. for C20H24N4O2, 352.19 m / z, found 353.10 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.52 (d, J = 4.8 Hz, 1H), 8.11 (d, J = 3.5 Hz, 1H), 7.71 (d, J = 8.4 Hz, 1H), 7.34 (s, 1H), 7.25 (q, J = 5.1 Hz, 1H), 7.21 – 7.21 (m, 1H), 6.97 (d, J = 8.8 Hz, 1H), 6.69 – 6.78 (m, 1H), 5.92 (s, 1H), 5.13 (s, 2H), 2.89 (d, J = 8.0 Hz, 2H), 2.64 (d, J = 8.4 Hz, 2H), 1.26 (s, 9H). Example 3: 1-(tert-butyl)-3-(2-oxo-1-(1-phenylethyl)-1,2,3,4-tetrahydroquinolin-6-yl)urea 6-nitro-1-(1-phenylethyl)-3,4-dihydroquinolin-2-one To a solution of 6-nitro-3,4-dihydro-1H-quinolin-2-one (500 mg, 2.602 mmol, 1 equiv) in DMF (10 mL) was added K2CO3 (1078.7 mg, 7.805 mmol, 3 equiv) and (1-bromoethyl)benzene (529.6 mg, 2.862 mmol, 1 equiv). The resulting mixture was stirred for 16 h at rt. The mixture was diuted with EtOAc (100 mL), washed with water (3 x 50 mL), brine (2 x 50 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 6-nitro-1-(1-phenylethyl)-3,4-dihydroquinolin-2-one (400 mg, 45.17%) as a white solid.MS (ESI): mass calcd. for C17H16N2O3296.12 m / z, found 297.05 [M+H]+. 6-amino-1-(1-phenylethyl)-3,4-dihydroquinolin-2-one To a solution of 6-nitro-1-(1-phenylethyl)-3,4-dihydroquinolin-2-one (400 mg, 1.350 mmol, 1 equiv) in EtOH (10 mL) and H2O (2.5 mL) was added Fe (753.8 mg, 13.499 mmol, 10 equiv) and NH4Cl (722.0 mg, 13.499 mmol, 10 equiv). The resulting mixture was stirred for 2 h at 60 °C. The reaction mixture was quenched by water and extracted with EA (3 x 30 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 6-amino-1-(1-phenylethyl)-3,4-dihydroquinolin-2- one (200 mg, 55.63%) as a white solid. 1-(tert-butyl)-3-(2-oxo-1-(1-phenylethyl)-1,2,3,4-tetrahydroquinolin-6-yl)urea To a solution of 6-amino-1-(1-phenylethyl)-3,4-dihydroquinolin-2-one (200 mg, 0.751 mmol, 1 equiv) in DCM (5 mL) was added 2-isocyanato-2-methylpropane (223.3 mg, 2.253 mmol, 3 equiv) and TEA (75.9 mg, 0.751 mmol, 1 equiv).The resulting mixture was stirred for overnight at rt. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) & Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 38% B to 50% B in 10.5 min; Wave Length: 254 / 220 nm; RT1(min): 10.7; Number Of Runs: 3) to afford 1-(tert-butyl)-3-(2-oxo-1-(1-phenylethyl)-1,2,3,4- tetrahydroquinolin-6-yl)urea (57.7 mg, 21.02%) as a white solid. MS (ESI): mass calcd. for C22H27N3O2, 365.21 m / z, found 366.15 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.07 (s, 1H), 7.18 – 7.39 (m, 6H), 6.81 (d, J = 8.8 Hz, 1H), 6.42 – 6.52 (m, 1H), 6.15 (d, J = 8.0 Hz, 1H), 5.91 (s, 1H), 2.80 (d, J = 5.6 Hz, 2H), 2.54 – 2.70 (m, 2H), 1.67 (t, J = 5.7 Hz, 3H), 1.24 (dd, J = 4.1, 2.2 Hz, 9H). Example 4: 1-(tert-butyl)-3-(1-((1-methyl-1H-pyrazol-3-yl)methyl)-2-oxo-1,2,3,4- tetrahydroquinolin-6-yl)urea 1-[(1-methylpyrazol-3-yl)methyl]-6-nitro-3,4-dihydroquinolin-2-one To a solution of 6-nitro-3,4-dihydro-1H-quinolin-2-one (500 mg, 2.602 mmol, 1 equiv) in DMF (10 mL) was added K2CO3 (1086.6 mg, 7.805 mmol, 3 equiv) and 3-(bromomethyl)-1- methylpyrazole (500.9 mg, 2.862 mmol, 1.1 equiv). The resulting mixture was stirred for 16 h at rt. The mixture was diuted with EtOAc (100 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 1-[(1-methylpyrazol-3-yl)methyl]-6-nitro- 3,4-dihydroquinolin-2-one (500 mg, 46.59%) as a white solid. MS (ESI): mass calcd. for C14H14N4O3: 286.11 m / z, found 287.00 [M+H]+. 6-amino-1-[(1-methylpyrazol-3-yl)methyl]-3,4-dihydroquinolin-2-one To a solution of 6-nitro-1-(1H-pyrazol-3-ylmethyl)-3,4-dihydroquinolin-2-one (300 mg, 1.102 mmol, 1 equiv) in EtOH (10 mL) and H2O (2.5 mL) was added Fe (615.3 mg, 11.019 mmol, 10 equiv) and NH4Cl (589.3 mg, 11.019 mmol, 10 equiv).The resulting mixture was stirred for 2 h at 60 °C and stirred until the starting material was totally consumed by TLC. The reaction mixture was quenched by water and extracted with EA (3 x 30 mL).The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) to afford 6-amino-1-[(1-methylpyrazol-3-yl)methyl]-3,4- dihydroquinolin-2-one (101 mg, 36.03%) as a yellow solid. 1-(tert-butyl)-3-(1-((1-methyl-1H-pyrazol-3-yl)methyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6- yl)urea To a solution of 6-amino-1-[(1-methylpyrazol-3-yl)methyl]-3,4-dihydroquinolin-2-one (50 mg, 0.195 mmol, 1 equiv) in DCM (5 mL) was added 2-isocyanato-2-methylpropane (58.0 mg, 0.585 mmol, 3 equiv) and TEA (19.7 mg, 0.195 mmol, 1 equiv).The resulting mixture was stirred for overnight at rt. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) & Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 17% B to 42% B in 9 min, 42% B; Wave Length: 254 / 220 nm; RT1(min): 8.9; Number Of Runs: 0) to afford 1-(tert-butyl)-3-(1-((1-methyl-1H- pyrazol-3-yl)methyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea (9.0 mg, 12.23%) as a white solid. MS (ESI): mass calcd. for C19H25N5O2, 355.20 m / z, found 356.10 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.10 (d, J = 5.2 Hz, 1H), 7.48 – 7.62 (m, 1H), 7.29 (s, 1H), 7.01 (s, 2H), 5.85 – 6.04 (m, 2H), 4.95 (s, 2H), 3.78 – 3.82 (m, 3H), 2.81 (s, 2H), 2.51 (s, 2H), 1.17 – 1.37 (m, 9H). Example 5: 1-(1-benzyl-3-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(tert-butyl)urea Synthetic Scheme 1-benzyl-3-methyl-6-nitro-3,4-dihydroquinolin-2(1H)-one To a solution of 1-benzyl-6-nitro-3,4-dihydroquinolin-2(1H)-one (1 g, 3.54 mmol, 1 equiv) in THF (70 mL) was added 2M LiHMDS (in THF) (2.3 mL, 4.60 mmol, 1.3 equiv) at -20 °C under N2. The resulting mixture was stirred 30 min at -20 °C. The reaction mixture was added MeI (653.6 mg, 4.60 mmol, 1.3 equiv) at -20 °C. The resulting mixture was stirred 30 min at -20 °C and then stirred 16 h at rt. The reaction mixture was quenched by water (50 mL) and extracted with EA (3 x 70 mL). The combined organic extracts were washed with brine (50 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 1-benzyl-3-methyl- 6-nitro-3,4-dihydroquinolin-2(1H)-one (0.3 g, 28.59%) as a white solid. 6-amino-1-benzyl-3-methyl-3,4-dihydroquinolin-2(1H)-one To a solution of 1-benzyl-3-methyl-6-nitro-3,4-dihydroquinolin-2(1H)-one (0.28 g, 0.944 mmol, 1 equiv) in EtOH (10 mL) and H2O (2.5 mL) was added Fe (527.7 mg, 9.44 mmol, 10 equiv) and NH4Cl (504.9 mg, 9.76 mmol, 10 equiv). The resulting mixture was stirred for 2 h at 60 °C and stirred until the starting material was totally consumed by TLC. The reaction mixture was quenched by water and extracted with EA (3 x 30 mL).The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) to afford 3-((6-amino-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl)benzonitrile (160 mg, 46.37%) as a yellow solid. MS (ESI): mass calcd. for C17H18N2O: 266.14 m / z, found 267.20 [M+H]+. 1-(tert-butyl)-3-(1-(3-cyanobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea To a solution of 6-amino-1-benzyl-3-methyl-3,4-dihydroquinolin-2(1H)-one (150 mg, 0.563 mmol, 1 equiv) in CH3CN (5 mL) was added 2-isocyanato-2-methylpropane (167.48 mg, 1.689 mmol, 3 equiv) and KHCO3(112.7 mg, 1.126 mmol, 2 equiv). The resulting mixture was stirred for overnight at 70 °C. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) & Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 17% B to 42% B in 9 min, 42% B; Wave Length: 254 / 220 nm; RT1(min): 8.9; Number Of Runs: 0) to afford 1-(tert-butyl)-3-(1-(3- cyanobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea (18.1 mg, 8.78%) as a white solid. MS (ESI): mass calcd. for C22H27N3O2: 365.21 m / z, found 366.10 [M+H]+.1H NMR (400 MHz, Chloroform-d) δ 7.26 – 7.31 (m, 2H), 7.12 – 7.23 (m, 3H), 6.82 (d, J = 8.7 Hz, 1H), 6.71 (d, J = 8.6 Hz, 1H), 6.25 – 6.54 (m, 1H), 5.19 (d, J = 16.3 Hz, 1H), 5.05 (d, J = 16.0 Hz, 1H), 2.94 (d, J = 11.6 Hz, 1H), 2.58 – 2.81 (m, 2H), 1.33 (s, 9H), 1.30 (d, J = 6.2 Hz, 3H). Example 6: 1-(tert-butyl)-3-(1-(3-chlorobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea 1-(3-chlorobenzyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one To a solution of 6-nitro-3,4-dihydro-1H-quinolin-2-one (500 mg, 2.602 mmol, 1 equiv) in dimethylformamide (10 mL) was added 1-(bromomethyl)-3-chlorobenzene (801.93 mg, 3.903 mmol, 1.5 equiv) and potassium methaneperoxoate potassium (724.41 mg, 5.204 mmol, 2.0 equiv) at rt. The mixture was stirred for overnight at rt. The reaction mixture was quenched by water (30 mL) and extracted with EA (3 x 30 mL). The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, and concentrated under vacuum. The residue was purified by silica gel column chromatography, eluted with PE / EA (3:1) to afford 1-(3- chlorobenzyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one (700 mg, 88.29%) as a white solid. MS (ESI): mass calcd. C16H13ClN2O3:for 316.06 m / z, found 317.10[M+H]+. 6-amino-1-(3-chlorobenzyl)-3,4-dihydroquinolin-2(1H)-one To a solution of 1-(3-chlorobenzyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one (700 mg, 2.210 mmol, 1 equiv) in EtOH (5 mL) / H2O (0.5 mL) was added Fe (1.2 g, 22.1 mmol, 10 equiv) and NH4Cl (1.2 g, 22.100 mmol, 10 equiv) at rt. The mixture was stirred for 2 h at 60 °C. The reaction mixture was quenched by water (30 mL) and extracted with EA (3 x 30 mL). The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, and concentrated under vacuum. The residue was purified by silica gel column chromatography, eluted with PE / EA (2:1) to afford 6-amino-1-(3-chlorobenzyl)-3,4-dihydroquinolin-2(1H)-one (600 mg, 94.68%) as a brown solid. MS (ESI): mass calcd. C16H15ClN2O: for 286.09 m / z, found 287.10[M+H]+. 1-(tert-butyl)-3-(1-(3-chlorobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea A solution of 6-amino-1-(3-chlorobenzyl)-3,4-dihydroquinolin-2(1H)-one (50 mg, 0.174 mmol, 1 equiv) in DCM (3 mL) was added TEA (35.29 mg, 0.348 mmol, 2.0 equiv) and 2- isocyanato-2-methylpropane (20.74 mg, 0.209 mmol, 1.2 equiv) at 0 °C. The resulting mixture was stirred for 16 h at rt. The reaction mixture was quenched by water (20 mL). The resulting mixture was extracted with DCM (3 x 30 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (2:1) to afford 1-(tert-butyl)-3-(1-(3-chlorobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea (30.4 mg, 45.11%) as white solid. MS (ESI): mass calcd. C21H24ClN3O2for : 385.16 m / z, found 386.1 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.12 (s, 1H), 7.24 – 7.40 (m, 4H), 7.15 – 7.18 (m, 1H), 6.96 – 7.01 (m, 1H), 6.75 – 6.80 (m, 1H), 5.92 (s, 1H), 5.10 (s, 2H), 2.85 – 2.92 (m, 2H), 2.61 – 2.70 (m, 2H), 1.27 (s, 9H). Example 7: 1-(4-benzyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-3-(tert-butyl)urea 4-benzyl-7-nitro-2H-1,4-benzoxazin-3-one To a solution of 7-nitro-2,4-dihydro-1,4-benzoxazin-3-one (400 mg, 2.060 mmol, 1 equiv) in DMF (10 mL) was added K2CO3(860.4 mg, 6.181 mmol, 3 equiv) and benzyl bromide (387.6 mg, 2.266 mmol, 1.1 equiv). The resulting mixture was stirred for 16 h at rt. The mixture was diuted with EtOAc (100 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 4-benzyl-7-nitro-2H-1,4-benzoxazin-3-one (500 mg, 72.97%) as a yellow solid. MS (ESI): mass calcd. for C15H12N2O4284.08 m / z, found 285.05 [M+H]+. 7-amino-4-benzyl-2H-1,4-benzoxazin-3-one To a solution of 4-benzyl-7-nitro-2H-1,4-benzoxazin-3-one (500 mg, 1.759 mmol, 1 equiv) in EtOH (10 mL) and H2O (2.5 mL) was added Fe (982.2 mg, 17.589 mmol, 10 equiv) and NH4Cl (940.8 mg, 17.589 mmol, 10 equiv). The resulting mixture was stirred for 2 h at 60 °C. The reaction mixture was quenched by water and extracted with EA (3 x 30 mL).The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) to afford 7-amino-4-benzyl-2H-1,4-benzoxazin-3-one (200 mg, 44.72%) as a yellow solid. MS (ESI): mass calcd. for C15H14N2O2, 254.11 m / z, found 255.05 [M+H]+. 1-(4-benzyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-3-(tert-butyl)urea To a solution of 7-amino-4-benzyl-2H-1,4-benzoxazin-3-one (150 mg, 0.590 mmol, 1 equiv) in DCM (5 mL) was added 2-isocyanato-2-methylpropane (175.4 mg, 1.770 mmol, 3 equiv) and TEA (59.6 mg, 0.590 mmol, 1 equiv). The resulting mixture was stirred for overnight at rt. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) & Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 17% B to 42% B in 9 min, 42% B; Wave Length: 254 / 220 nm; RT1(min): 8.9; Number Of Runs: 0) to afford 1-(4-benzyl-3-oxo-3,4-dihydro-2H- benzo[b][1,4]oxazin-7-yl)-3-(tert-butyl)urea (56.8 mg, 27.14%) as a white solid. MS (ESI): mass calcd. for C20H23N3O3, 353.17 m / z, found 354.15 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.21 (s, 1H), 7.17 – 7.41 (m, 7H), 6.86 (dd, J = 8.6, 2.1 Hz, 1H), 6.71 – 6.82 (m, 1H), 5.93 (s, 1H), 5.11 (s, 2H), 4.74 (d, J = 2.1 Hz, 2H), 1.26 (d, J = 2.1 Hz, 9H). Example 8: 1-(tert-butyl)-3-(1-(2-chlorobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea 1-(2-chlorobenzyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one To a solution of 6-nitro-3,4-dihydroquinolin-2(1H)-one (500 mg, 2.602 mmol, 1 equiv) in DMF (10 mL) was added K2CO3(1086.6 mg, 7.805 mmol, 3 equiv) and 1-(bromomethyl)-2- chlorobenzene (583.64 mg, 2.862 mmol, 1.1 equiv). The resulting mixture was stirred for 16 h at rt. The mixture was diuted with EtOAc (50 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 1-(2-chlorobenzyl)-6-nitro-3,4- dihydroquinolin-2(1H)-one (400 mg, 48.54%) as a white solid. MS (ESI): mass calcd. for C16H13ClN2O3: 316.06 m / z, found 317.00 [M+H]+. 6-amino-1-(2-chlorobenzyl)-3,4-dihydroquinolin-2(1H)-one To a solution of 1-(2-chlorobenzyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one (400 mg, 1.263 mmol, 1 equiv) in EtOH (10 mL) and H2O (2.5 mL) was added Fe (705.3 mg, 12.63 mmol, 10 equiv) and NH4Cl (675.6 mg, 12.63 mmol, 10 equiv).The resulting mixture was stirred for 2 h at 60 °C and stirred until the starting material was totally consumed by TLC. The reaction mixture was quenched by water and extracted with EA (3 x 30 mL).The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) to afford 6-amino-1-(2-chlorobenzyl)-3,4-dihydroquinolin-2(1H)-one (0.3 g, 82.87%) as a yellow solid. MS (ESI): mass calcd. for C16H15ClN2O: 286.09 m / z, found 287.00 [M+H]+. 1-(tert-butyl)-3-(1-(2-chlorobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea To a solution of 6-amino-1-(2-chlorobenzyl)-3,4-dihydroquinolin-2(1H)-one (100 mg, 0.349 mmol, 1 equiv) in DCM (5 mL) was added 2-isocyanato-2-methylpropane (103.9 mg, 1.048 mmol, 3 equiv) and TEA (105.8 mg, 1.048 mmol, 3 equiv). The resulting mixture was stirred for overnight at rt. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) & Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 17% B to 42% B in 9 min, 42% B; Wave Length: 254 / 220 nm; RT1(min): 8.9; Number Of Runs: 0) to afford 1-(tert-butyl)-3-(1-(2-chlorobenzyl)- 2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea (39.7 mg, 29.40%) as a white solid. MS (ESI): mass calcd. for C21H24ClN3O2: 385.16 m / z, found 386.05 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.12 (s, 1H), 7.47 – 7.56 (m, 1H), 7.35 – 7.42 (m, 1H), 7.26 (d, J = 8.7 Hz, 2H), 6.92 – 7.01 (m, 2H), 6.47 – 6.62 (m, 1H), 5.91 (s, 1H), 5.07 (s, 2H), 2.88 – 2.96 (m, 2H), 2.63 – 2.72 (m, 2H), 1.25 (s, 9H). Example 9: tert-butyl (1-benzyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)carbamate Synthetic Scheme tert-butyl (1-benzyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)carbamate To a solution of 6-amino-1-benzyl-3,4-dihydroquinolin-2(1H)-one (100 mg, 0.396 mmol, 1 equiv) in DCM (6 mL) was added Boc2O (129.7 mg, 0.594 mmol, 1.5 equiv) and DMAP (72.6 mg, 0.594 mmol, 1.5 equiv). The resulting mixture was stirred for 5 h at rt. The mixture was diuted with DCM (30 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 17% B to 45% B in 9 min, 45% B; Wave Length: 254 / 220 nm; RT1(min): 8.6; Number Of Runs: 0) to afford tert-butyl (1- benzyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)carbamate (19.4 mg, 10.21%) as a yellow solid. MS (ESI): mass calcd. for C21H24N2O3: 352.18 m / z, found 353.10 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 9.21 (s, 1H), 7.39 – 7.16 (m, 6H), 7.10 (dd, J = 9.0, 2.4 Hz, 1H), 6.82 (d, J = 8.8 Hz, 1H), 5.11 (s, 2H), 2.88 (t, J = 7.2 Hz, 2H), 2.66 (dd, J = 8.7, 6.0 Hz, 2H), 1.45 (s, 9H). Example 10: 1-(1-benzyl-4,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(tert- butyl)urea Synthetic Scheme 4,4-dimethyl-6-nitro-3,4-dihydroquinolin-2(1H)-one To a solution of 4,4-dimethyl-3,4-dihydroquinolin-2(1H)-one (0.4 g, 2.28 mmol, 1 equiv) in H2O (2 mL) and H2SO4 (9 mL) was added HNO3 (0.3 mL) at -10 °C. The reaction was stirred for 2 h at -10-0 °C. The reaction mixture was quenched by water. The mixture was acidified pH = 7 with NaHCO3 (aq.) and then extracted with EA (3 x 50 mL). The combined organic extracts were washed with brine (50 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 4,4-dimethyl-6-nitro-3,4-dihydroquinolin-2(1H)-one (0.3 g, 59.76%) as a white solid. MS (ESI): mass calcd. for C11H12N2O3, 220.08 m / z, found 221.10 [M+H]+ . 1-benzyl-4,4-dimethyl-6-nitro-3,4-dihydroquinolin-2(1H)-one To a solution of 4,4-dimethyl-6-nitro-3,4-dihydroquinolin-2(1H)-one (280 mg, 1.270 mmol, 1 equiv) in CH3CN (10 mL) was added Cs2CO3(828.3 mg, 2.542 mmol, 2.0 equiv) and (bromomethyl)benzene (238.9 mg, 1.397 mmol, 1.1 equiv). The resulting mixture was stirred for 16 h at rt. The mixture was diuted with EtOAc (50 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 1-benzyl-4,4-dimethyl-6-nitro-3,4- dihydroquinolin-2(1H)-one (300 mg, 76.14%) as a white solid. MS (ESI): mass calcd. for C18H18N2O3: 310.13 m / z, found 311.25 [M+H]+. 6-amino-1-benzyl-4,4-dimethyl-3,4-dihydroquinolin-2(1H)-one To a solution of 1-benzyl-4,4-dimethyl-6-nitro-3,4-dihydroquinolin-2(1H)-one (280 mg, 0.902 mmol, 1 equiv) in EtOH (10 mL) and H2O (2.5 mL) was added Fe (503.9 mg, 9.02 mmol, 10 equiv) and NH4Cl (482.5 mg, 9.02 mmol, 10 equiv). The resulting mixture was stirred for 2 h at 60 °C and stirred until the starting material was totally consumed by TLC. The reaction mixture was quenched by water and extracted with EA (3 x 30 mL).The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) to afford 6-amino-1-benzyl-4,4-dimethyl-3,4-dihydroquinolin-2(1H)-one (100 mg, 39.68%) as a yellow solid. MS (ESI): mass calcd. for C18H20N2O: 280.16 m / z, found 281.20 [M+H]+. 1-(1-benzyl-4,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(tert-butyl)urea To a solution of 6-amino-1-benzyl-4,4-dimethyl-3,4-dihydroquinolin-2(1H)-one (100 mg, 0.357 mmol, 1 equiv) in DCM (5 mL) was added 2-isocyanato-2-methylpropane (106.1 mg, 1.07 mmol, 3 equiv) and TEA (108.1 mg, 1.07 mmol, 3 equiv). The resulting mixture was stirred for overnight at rt. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) & Prep-HPLC (Column: XBridge Prep C18 OBD Column, 30*50 mm, 5μm 13nm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 26% B to 45% B in 9 min, 45% B; Wave Length: 254 / 220 nm; RT1(min): 8.9; Number Of Runs: 0) to afford 1-(1-benzyl-4,4-dimethyl-2-oxo-1,2,3,4- tetrahydroquinolin-6-yl)-3-(tert-butyl)urea (51.0 mg, 37.50%) as a white solid. MS (ESI): mass calcd. for C23H29N3O2: 379.23 m / z, found 380.15 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.16 (s, 1H),7.38 (s, 1H),7.20 - 7.31 (m, 5H),7.02 (s, 1H), 6.86 (s, 1H), 5.88 (s, 1H), 5.13 (s, 2H), 2.50 - 2.55 (s, 2H), 1.26 (s, 9H), 1.22 (s, 6H). Example 11: 1-(1-benzyl-3-(methoxymethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(tert- butyl)urea Synthetic Scheme

[0006] 1-benzyl-3-(methoxymethyl)-6-nitro-3,4-dihydroquinolin-2-one To a solution of 1-benzyl-6-nitro-3,4-dihydroquinolin-2-one (1.3 g, 4.605 mmol, 1 equiv) in THF (40 mL) was added 2M LDA (in THF) (3.5 mL, 0.74 g, 6.907 mmol, 1.5 equiv) at -78 °C under N2. The resulting mixture was stirred 30 min at -78 °C. The reaction mixture was added bromo(methoxy)methane (1.15 g, 9.203 mmol, 2.00 equiv) at -78 °C. The resulting mixture was stirred for 1 h at -78 °C and 16 h at rt. The reaction mixture was quenched by NH4Cl (aq.) and extracted with EA (3 x 50 mL). The combined organic extracts were washed with brine (30 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 1-benzyl-3- (methoxymethyl)-6-nitro-3,4-dihydroquinolin-2-one (400 mg, 12.30%) as a yellow solid. MS (ESI): mass calcd. for C18H18N2O4, 326.13 m / z, found 327.05 [M+H]+. 6-amino-1-benzyl-3-(methoxymethyl)-3,4-dihydroquinolin-2-one To a solution of 1-benzyl-3-(methoxymethyl)-6-nitro-3,4-dihydroquinolin-2-one (300 mg, 0.919 mmol, 1 equiv) in EtOH (10 mL) and H2O (2.5 mL) was added Fe (513.3 mg, 9.193 mmol, 10 equiv) and NH4Cl (491.7 mg, 9.193 mmol, 10 equiv). The resulting mixture was stirred for 2 h at 60 °C. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) to afford 6-amino-1-benzyl-3-(methoxymethyl)-3,4- dihydroquinolin-2-one (200 mg, 26.38%) as a yellow solid. MS (ESI): mass calcd. for C18H20N2O2, 296.15 m / z, found 297.10 [M+H]+. 1-(1-benzyl-3-(methoxymethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(tert-butyl)urea To a solution of 6-amino-1-benzyl-3-(methoxymethyl)-3,4-dihydroquinolin-2-one (100 mg, 0.337 mmol, 1 equiv) in DCM (5 mL) was added 2-isocyanato-2-methylpropane (100.3 mg, 1.012 mmol, 3 equiv) and TEA (102.4 mg, 1.012 mmol, 3 equiv).The resulting mixture was stirred for overnight at rt. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) & Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 17% B to 42% B in 9 min, 42% B; Wave Length: 254 / 220 nm; RT1(min): 8.9; Number Of Runs: 0) to afford 1-(1-benzyl-3-(methoxymethyl)-2- oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(tert-butyl)urea (12.1 mg, 8.95%) as a white solid. MS (ESI): mass calcd. for C23H29N3O3, 395.22 m / z, found 396.20 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.01 (s, 1H), 7.19 (d, J = 5.5 Hz, 3H), 7.04 – 7.17 (m, 3H), 6.90 (d, J = 8.7 Hz, 1H), 6.66 (d, J = 9.1 Hz, 1H), 5.83 (s, 1H), 4.99 (s, 2H), 3.53 – 3.64 (m, 1H), 3.46 (t, J = 8.2 Hz, 1H), 3.20 (d, J = 1.7 Hz, 3H), 2.60 – 2.95 (m, 3H), 1.16 (d, J = 1.7 Hz, 9H). Example 12: 1-(1-benzyl-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-6-yl)-3-(tert-butyl)ur ea Synthetic Scheme 2-(benzylamino)-5-nitrobenzonitrile To a solution of 2-fluoro-5-nitrobenzonitrile (5 g, 30.100 mmol, 1 equiv) in ACN (100 mL) was added benzylamine (4.84 g, 45.150 mmol, 1.5 equiv) and K2CO3(8.32 g, 60.200 mmol, 2 equiv). The reaction was stirred at rt for 1 hour. Quenched with water (20 mL) and extracted with EA (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 2-(benzylamino)-5-nitrobenzonitrile (6.875 g, 90.18%) as a yellow solid. MS(ESI): mass calcd. for C14H11N3O2: 253.26 m / z, found 254.00[M+H]+. 2-(aminomethyl)-N-benzyl-4-nitroaniline To a solution of 2-(benzylamino)-5-nitrobenzonitrile (400 mg, 1.579 mmol, 1 equiv) in THF (20 mL) was added NaBH4 (238.99 mg, 6.316 mmol, 4 equiv) and Boron trifluoride diethyl etherate (896.66 mg, 6.316 mmol, 4 equiv). The reaction was stirred at 0 °C for 0.5h. The reaction was quenched with water (10 mL) and extracted with EA (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with DCM / MeOH (0-30%) to give 2-(aminomethyl)-N-benzyl-4-nitroaniline (41 mg, 10.09%) as a yellow solid. MS (ESI): mass calcd for C14H15N3O2: 257.29 m / z, found 258.10 [M+H]+. 1-benzyl-6-nitro-3,4-dihydroquinazolin-2(1H)-one To a solution of 2-(aminomethyl)-N-benzyl-4-nitroaniline (260 mg, 1.011 mmol, 1 equiv) in THF (20 mL) was added CDI (163.86 mg, 1.011 mmol, 1 equiv) at 0 °C. The reaction was stirred at rt for 15 min. To the above mixture was added CDI (327.71 mg, 2.022 mmol, 2 equiv) dropwise at 0 °C. The resulting mixture was stirred for additional 15 min at rt. After the final reaction mixture was stirred for 18 h at 70 °C. Quenched with water (10 mL) and extracted with EA (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 1-benzyl-6-nitro-3,4-dihydroquinazolin-2-one (198 mg, 69.17%) as a white solid. MS (ESI): mass calcd. for C15H13N3O3: 283.29 m / z, found 284.05 [M+H]+. 1-benzyl-3-methyl-6-nitro-3,4-dihydroquinazolin-2(1H)-one To a solution of 1-benzyl-6-nitro-3,4-dihydroquinazolin-2-one (184 mg, 0.650 mmol, 1 equiv) in THF (20 mL) was added NaH (23.38 mg, 0.975 mmol, 1.5 equiv) at 0°C. The reaction was stirred at 0°C for 30 min. To the above mixture was added MeI (184.38 mg, 1.300 mmol, 2 equiv) dropwise at 0 °C. The final reaction mixture was stirred for 1h at rt. Quenched with water (50 mL) and extracted with EA (3 x 50 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 1-benzyl-3-methyl-6-nitro-4H- quinazolin-2-one (122 mg, 63.18%) as a white solid. MS (ESI): mass calcd. for C16H15N3O3: 297.31 m / z, found 298.00 [M+H]+. 6-amino-1-benzyl-3-methyl-3,4-dihydroquinazolin-2(1H)-one To a solution of 1-benzyl-3-methyl-6-nitro-4H-quinazolin-2-one (122 mg, 0.410 mmol, 1 equiv) in MeOH (10 mL) was added Pd / C (10%, 122 mg) at rt. The mixture was hydrogenated at room temperature under 30 psi of hydrogen pressure for 1h. The resulting mixture was filtered, the filter cake was washed with MeOH (3 x 10 mL). The filtrate was concentrated under reduced pressure. This resulted in 6-amino-1-benzyl-3-methyl-4H-quinazolin-2-one (110 mg, 100.28%) as a white solid. MS (ESI): mass calcd. for C16H17N3O: 267.33 m / z, found 268.20 [M+H]+. 1-(1-benzyl-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-6-yl)-3-(tert-butyl)urea To a solution of 6-amino-1-benzyl-3-methyl-4H-quinazolin-2-one (100 mg, 0.374 mmol, 1 equiv) in DCM (10 mL, 157.306 mmol, 420.53 equiv) was added 2-isocyanato-2- methylpropane (370.82 mg, 3.740 mmol, 10 equiv) and Pyridine (295.89 mg, 3.740 mmol, 10 equiv). The reaction was stirred at rt for 3 days. Quenched with water (10 mL) and extracted with EA (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by preparative HPLC using a YMC-Actus Triart C18, 30*150 mm, 5μm column (eluent: 36% to 56% (v / v) CH3CN and H2O with 10mmol / L NH4HCO3) to afford the title compound 1-(1-benzyl-3-methyl-2-oxo-4H-quinazolin- 6-yl)-3-tert-butylurea (23.2 mg, 16.92%) as a white solid. MS (ESI): mass calcd. for C21H26N4O2:366.47 m / z, found:367.20 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 7.90 – 8.21 (m, 1H), 7.18 – 7.39 (m, 6H), 6.80 – 7.00 (m, 1H), 6.44 – 6.68 (m, 1H), 5.72 – 5.99 (m, 1H), 4.90 – 5.20 (m, 2H), 4.28 – 4.51 (m, 2H), 2.80 – 3.01 (m, 3H), 1.20 – 1.31 (m, 9H). Example 13: (S)-1-(tert-butyl)-3-(2-oxo-1-(1-phenylethyl)-1,2,3,4-tetrahydroquinolin-6-yl)u rea Synthetic Scheme

[0007] (S)-6-nitro-1-(1-phenylethyl)-3,4-dihydroquinolin-2(1H)-one To a solution of (R)-1-phenylethanol (1 g, 8.186 mmol, 1 equiv) in DCM (30 mL) was added 6-nitro-3,4-dihydro-1H-quinolin-2-one (1.57 g, 8.186 mmol, 1 equiv) and PPh3(2.15 g, 8.186 mmol, 1 equiv). DEAD (1.43 g, 8.211 mmol, 1 equiv) was added the mixture at 0 °C under a nitrogen atmosphere. The resulting mixture was stirred for 16 h at rt. The reaction mixture was quenched by water and extracted with EA (3 x 50 mL). The combined organic extracts were washed with brine (50 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford (S)-6-nitro-1-(1-phenylethyl)-3,4-dihydroquinolin-2(1H)-one (300 mg, 11.61%) as a yellow solid. MS (ESI): mass calcd. for C17H16N2O3, 296.12 m / z, found 297.15 [M+H]+. (S)-6-amino-1-(1-phenylethyl)-3,4-dihydroquinolin-2(1H)-one To a solution of (S)-6-nitro-1-(1-phenylethyl)-3,4-dihydroquinolin-2(1H)-one (280 mg, 0.945 mmol, 1 equiv) in MeOH (10 mL) was added Pd / C (30 mg). The reaction mixture was then stirred for 1 h under hydrogen atmosphere (balloon). The reaction mixture was filtered through a pad of Celite and concentrated under reduced pressure to afford (S)-6-amino-1-(1- phenylethyl)-3,4-dihydroquinolin-2(1H)-one (220 mg, 86.81%) as a yellow solid. MS (ESI): mass calcd. for C17H18N2O, 266.14 m / z, found 267.15 [M+H]+. (S)-1-(tert-butyl)-3-(2-oxo-1-(1-phenylethyl)-1,2,3,4-tetrahydroquinolin-6-yl)urea To a stirred solution of (S)-6-amino-1-(1-phenylethyl)-3,4-dihydroquinolin-2(1H)-one (200 mg, 0.751 mmol, 1 equiv) in DCM (10.00 mL) was added 2-isocyanato-2-methylpropane (372.2 mg, 3.755 mmol, 5 equiv) and TEA (227.9 mg, 2.253 mmol, 3 equiv) stirred overnight at rt. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL).The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column eluted with PE / EA (2:1) & Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 17% B to 42% B in 9 min, 42% B; Wave Length: 254 / 220 nm; RT1(min): 8; Number Of Runs: 0) to afford (S)-1-(tert-butyl)-3-(2-oxo-1-(1-phenylethyl)- 1,2,3,4-tetrahydroquinolin-6-yl)urea (73.9 mg, 26.88%) as a white solid. MS (ESI): mass calcd. for C22H27N3O2, 365.21 m / z, found 366.20 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.07 (s, 1H), 7.18 – 7.39 (m, 6H), 6.81 (d, J = 8.8 Hz, 1H), 6.42 – 6.52 (m, 1H), 6.15 (d, J = 8.0 Hz, 1H), 5.91 (s, 1H), 2.80 (d, J = 5.6 Hz, 2H), 2.54 – 2.70 (m, 2H), 1.67 (t, J = 5.7 Hz, 3H), 1.24 (dd, J = 4.1, 2.2 Hz, 9H). Example 14: (R)-1-(tert-butyl)-3-(2-oxo-1-(1-phenylethyl)-1,2,3,4-tetrahydroquinolin-6-yl)u (R)-6-nitro-1-(1-phenylethyl)-3,4-dihydroquinolin-2(1H)-one To a solution of (S)-1-phenylethanol (1 g, 8.186 mmol, 1 equiv) in DCM (30 mL) was added 6-nitro-3,4-dihydro-1H-quinolin-2-one (1.57 g, 8.186 mmol, 1 equiv) and PPh3(2.15 g, 8.186 mmol, 1 equiv). DEAD (1.43 g, 8.211 mmol, 1 equiv) was added the mixture at 0 °C under a nitrogen atmosphere. The resulting mixture was stirred for 16 h at rt. The reaction mixture was quenched by water and extracted with EA (3 x 50 mL). The combined organic extracts were washed with brine (50 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford (R)-6-nitro-1-(1-phenylethyl)-3,4-dihydroquinolin-2(1H)-one (300 mg, 11.61%) as a yellow solid. MS (ESI): mass calcd. for C17H16N2O3, 296.12 m / z, found 297.15 [M+H]+. (R)-6-amino-1-(1-phenylethyl)-3,4-dihydroquinolin-2(1H)-one To a solution of (R)-6-nitro-1-(1-phenylethyl)-3,4-dihydroquinolin-2(1H)-one (280 mg, 0.945 mmol, 1 equiv) in MeOH (10 mL) was added Pd / C (30 mg). The reaction mixture was then stirred for 1 h under hydrogen atmosphere (balloon). The reaction mixture was filtered through a pad of Celite and concentrated under reduced pressure to afford (R)-6-amino-1-(1- phenylethyl)-3,4-dihydroquinolin-2(1H)-one (220 mg, 86.81%) as a yellow solid. MS (ESI): mass calcd. for C17H18N2O, 266.14 m / z, found 267.15 [M+H]+. (R)-1-(tert-butyl)-3-(2-oxo-1-(1-phenylethyl)-1,2,3,4-tetrahydroquinolin-6-yl)urea To a stirred solution of (R)-6-amino-1-(1-phenylethyl)-3,4-dihydroquinolin-2(1H)-one (200 mg, 0.751 mmol, 1 equiv) in DCM (10.00 mL) was added 2-isocyanato-2-methylpropane (372.2 mg, 3.755 mmol, 5 equiv) and TEA (227.9 mg, 2.253 mmol, 3 equiv) stirred overnight at rt. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL).The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column eluted with PE / EA (2:1) & Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 17% B to 42% B in 9 min, 42% B; Wave Length: 254 / 220 nm; RT1(min): 8.9; Number Of Runs: 0) to afford 3-tert-butyl-1-{2-oxo-1-[(1R)-1-phenylethyl]-3,4- dihydroquinolin-6-yl}urea (70 mg, 25.46%) as a white solid. MS (ESI): mass calcd. for C22H27N3O2, 365.21 m / z, found 366.20 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.07 (s, 1H), 7.18 – 7.39 (m, 6H), 6.81 (d, J = 8.8 Hz, 1H), 6.42 – 6.52 (m, 1H), 6.15 (d, J = 8.0 Hz, 1H), 5.91 (s, 1H), 2.80 (d, J = 5.6 Hz, 2H), 2.54 – 2.70 (m, 2H), 1.67 (t, J = 5.7 Hz, 3H), 1.24 (dd, J = 4.1, 2.2 Hz, 9H). Example 15: 1-(1-benzyl-4-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(tert-butyl)urea 4-methyl-6-nitro-3,4-dihydroquinolin-2(1H)-one To a solution of 4-methyl-3,4-dihydroquinolin-2(1H)-one (0.4 g, 2.48 mmol, 1 equiv) in H2O (2 mL) and H2SO4(9 mL) was added HNO3(0.3 mL) at -10 °C. The reaction was stirred for 2 h at -10-0 °C. The reaction mixture was quenched by water. The mixture was acidified pH = 7 with NaHCO3(aq.) and then extracted with EA (3 x 50 mL). The combined organic extracts were washed with brine (50 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 4-methyl-6-nitro-3,4-dihydroquinolin-2(1H)-one (0.28 g, 54.79%) as a white solid. MS (ESI): mass calcd. for C10H10N2O3, 206.07 m / z, found 207.05 [M+H]+. 1-benzyl-4-methyl-6-nitro-3,4-dihydroquinolin-2(1H)-one To a solution of 4-methyl-6-nitro-3,4-dihydroquinolin-2(1H)-one (260 mg, 1.260 mmol, 1 equiv) in DMF (10 mL) was added K2CO3 (522.0 mg, 3.782 mmol, 3 equiv) and (bromomethyl)benzene (237.1 mg, 1.386 mmol, 1.1 equiv). The resulting mixture was stirred for 16 h at rt. The mixture was diuted with EtOAc (50 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 1-benzyl-4-methyl-6-nitro-3,4- dihydroquinolin-2(1H)-one (200 mg, 53.62%) as a white solid. MS (ESI): mass calcd. for C17H16N2O3: 296.12 m / z, found 297.05 [M+H]+. 6-amino-1-benzyl-4-methyl-3,4-dihydroquinolin-2(1H)-one To a solution of 1-benzyl-4-methyl-6-nitro-3,4-dihydroquinolin-2(1H)-one (180 mg, 0.607 mmol, 1 equiv) in EtOH (10 mL) and H2O (2.5 mL) was added Fe (339.3 mg, 6.07 mmol, 10 equiv) and NH4Cl (324.7 mg, 6.07 mmol, 10 equiv). The resulting mixture was stirred for 2 h at 60 °C and stirred until the starting material was totally consumed by TLC. The reaction mixture was quenched by water and extracted with EA (3 x 30 mL).The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) to afford 6-amino-1-benzyl-4-methyl-3,4-dihydroquinolin-2(1H)-one (120 mg, 74.07%) as a yellow solid. MS (ESI): mass calcd. for C17H18N2O: 266.14 m / z, found 267.15 [M+H]+. 1-(1-benzyl-4-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(tert-butyl)urea To a solution of 6-amino-1-benzyl-4-methyl-3,4-dihydroquinolin-2(1H)-one (120 mg, 0.451 mmol, 1 equiv) in DCM (5 mL) was added 2-isocyanato-2-methylpropane (133.9 mg, 1.351 mmol, 3 equiv) and TEA (136.4 mg, 1.351 mmol, 3 equiv). The resulting mixture was stirred for overnight at rt. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) & Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 17% B to 42% B in 9 min, 42% B; Wave Length: 254 / 220 nm; RT1(min): 8.9; Number Of Runs: 0) to afford 1-(1-benzyl-4-methyl-2-oxo-1,2,3,4- tetrahydroquinolin-6-yl)-3-(tert-butyl)urea (47.9 mg, 44.35%) as a white solid. MS (ESI): mass calcd. for C22H27N3O2: 365.21 m / z, found 366.15 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.12 (s, 1H), 7.21 – 7.32 (m, 6H), 6.99 (dd, J = 8.8, 2.4 Hz, 1H), 6.82 (d, J = 8.8 Hz, 1H), 5.90 (s, 1H), 5.05 – 5.17 (m, 2H), 2.90 – 3.13 (m, 1H), 2.68 – 2.86 (m, 1H), 2.33 – 2.50 (m, 1H), 1.26 (s, 9H), 1.18 (d, J = 6.9 Hz, 3H). Example 16: 1-(1-benzyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(4-hydroxy-2- methylbutan-2-yl)urea Synthetic Scheme 6-amino-1-benzyl-3,4-dihydroquinolin-2(1H)-one A solution of 1-benzyl-6-nitro-3,4-dihydroquinolin-2-one (400 mg, 1.417 mmol, 1 equiv) in EtOH (10 mL) and H2O (2 mL) was treated with Fe (791.29 mg, 14.170 mmol, 10 equiv) and NH4Cl (757.92 mg, 14.170 mmol, 10 equiv) for 2 h at 60 °C.The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with DCM / MeOH (5%-11%) to afford 6-amino-1-benzyl-3,4- dihydroquinolin-2-one (320 mg, 89.51%) as a white solid. MS (ESI): mass calcd. for C16H16N2O, 252.13m / z, found 253.25 [M+H]+. 1-benzyl-6-isocyanato-3,4-dihydroquinolin-2(1H)-one To a stirred solution of 6-amino-1-benzyl-3,4-dihydroquinolin-2-one (180 mg, 0.713 mmol, 1 equiv) in anhydrous DCM (5 mL) was added TEA (216.57 mg, 2.139 mmol, 3 equiv) and Triphosgene (105.84 mg, 0.356 mmol, 0.5 equiv) at 0 °C, and stirred for 2 h at rt. After completion of reaction to afford 1-benzyl-6-isocyanato-3,4-dihydroquinolin-2-one as a crude. MS (ESI): mass calcd. for C17H14N2O2, 278.11m / z, found 279.05 [M+H]+ 1-(1-benzyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(4-hydroxy-2-methylbutan-2-yl)urea To a stirred solution of 1-benzyl-6-isocyanato-3,4-dihydroquinolin-2-one (crude) in anhydrous DCM (5 mL) was added 3-amino-3-methylbutan-1-ol (220.3 mg, 2.139 mmol, 3 equiv) was added at 0 °C. The resulting mixture was stirred for 1 h at rt. Desired product could be detected by LCMS. The resulting mixture was concentrated under reduced pressure. The crude product was purified by HPLC with the following conditions Column: XBridge Shield RP18 OBD Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 21% B to 41% B in 10 min, 41% B; Wave Length: 254 / 220 nm; RT1(min): 10; Number Of Runs: 0; to afford 1-(1-benzyl-2-oxo-3,4- dihydroquinolin-6-yl)-3-(4-hydroxy-2-methylbutan-2-yl)urea (23.3 mg, 16.47%) as a white solid. MS (ESI): mass calcd. for C22H27N3O3: 381.21 m / z, found 382.15 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.18 (s, 1H), 7.39 – 7.12 (m, 6H), 6.96 (dd, J = 8.8, 2.5 Hz, 1H), 6.77 (d, J = 8.8 Hz, 1H), 5.93 (s, 1H), 5.10 (s, 2H), 4.39 (t, J = 4.9 Hz, 1H), 3.48 (td, J = 7.1, 4.7 Hz, 2H), 2.88 (dd, J = 8.8, 5.8 Hz, 2H), 2.65 (dd, J = 8.8, 5.8 Hz, 2H), 1.79 (t, J = 7.2 Hz, 2H), 1.25 (s, 6H). Example 17: 1-(tert-butyl)-3-(1-(4-cyanobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea 4-((6-nitro-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl)benzonitrile To a solution of 6-nitro-3,4-dihydroquinolin-2(1H)-one (500 mg, 2.602 mmol, 1 equiv) in DMF (10 mL) was added K2CO3 (1086.6 mg, 7.805 mmol, 3 equiv) and 4- (bromomethyl)benzonitrile (558.09 mg, 2.862 mmol, 1.1 equiv). The resulting mixture was stirred for 16 h at rt. The mixture was diuted with EtOAc (50 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 4-((6-nitro-2-oxo-3,4- dihydroquinolin-1(2H)-yl)methyl)benzonitrile (400 mg, 50.00%) as a white solid. MS (ESI): mass calcd. for C17H13N3O3: 307.10 m / z, found 308.15 [M+H]+. 4-((6-amino-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl)benzonitrile To a solution of 4-((6-nitro-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl)benzonitrile (300 mg, 0.976 mmol, 1 equiv) in EtOH (10 mL) and H2O (2.5 mL) was added Fe (545.1 mg, 9.76 mmol, 10 equiv) and NH4Cl (522.1 mg, 9.76 mmol, 10 equiv).The resulting mixture was stirred for 2 h at 60 °C and stirred until the starting material was totally consumed by TLC. The reaction mixture was quenched by water and extracted with EA (3 x 30 mL).The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) to afford 4-((6-amino-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl)benzonitrile (108 mg, 40.05%) as a yellow solid. MS (ESI): mass calcd. for C17H15N3O: 277.12 m / z, found 278.25 [M+H]+. 1-(tert-butyl)-3-(1-(4-cyanobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea To a solution of 4-((6-amino-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl)benzonitrile (80 mg, 0.288 mmol, 1 equiv) in DCM (5 mL) was added 2-isocyanato-2-methylpropane (85.8 mg, 0.865 mmol, 3 equiv) and TEA (87.4 mg, 0.865 mmol, 3 equiv). The resulting mixture was stirred for overnight at rt. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) & Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 25% B to 45% B in 10.5 min; Wave Length: 220 nm; RT1(min): 12; Number Of Runs: 1) to afford 1-(tert-butyl)-3-(1-(4-cyanobenzyl)-2-oxo-1,2,3,4- tetrahydroquinolin-6-yl)urea (38.9 mg, 36.02%) as a white solid. MS (ESI): mass calcd. for C22H24N4O: 376.19 m / z, found 377.10 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.12 (s, 1H), 7.75 – 7.81 (m, 2H), 7.40 (d, J = 8.2 Hz, 2H), 7.34 (d, J = 2.4 Hz, 1H), 6.97 (dd, J = 8.8, 2.5 Hz, 1H), 6.71 (d, J = 8.8 Hz, 1H), 5.92 (s, 1H), 5.18 (s, 2H), 2.86 – 2.94 (m, 2H), 2.63 – 2.71 (m, 2H), 1.26 (s, 9H). Example 18: 1-(tert-butyl)-3-(1-(3-cyanobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea 3-((6-nitro-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl)benzonitrile To a solution of 6-nitro-3,4-dihydroquinolin-2(1H)-one (500 mg, 2.602 mmol, 1 equiv) in DMF (10 mL) was added K2CO3(1086.6 mg, 7.805 mmol, 3 equiv) and 3- (bromomethyl)benzonitrile (558.09 mg, 2.862 mmol, 1.1 equiv). The resulting mixture was stirred for 16 h at rt. The mixture was diuted with EtOAc (50 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 3-((6-nitro-2-oxo-3,4- dihydroquinolin-1(2H)-yl)methyl)benzonitrile (350 mg, 43.75%) as a white solid. MS (ESI): mass calcd. for C17H13N3O3: 307.10 m / z, found 308.05 [M+H]+. 3-((6-amino-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl)benzonitrile To a solution of 3-((6-nitro-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl)benzonitrile (300 mg, 0.976 mmol, 1 equiv) in EtOH (10 mL) and H2O (2.5 mL) was added Fe (545.1 mg, 9.76 mmol, 10 equiv) and NH4Cl (522.1 mg, 9.76 mmol, 10 equiv).The resulting mixture was stirred for 2 h at 60 °C and stirred until the starting material was totally consumed by TLC. The reaction mixture was quenched by water and extracted with EA (3 x 30 mL).The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) to afford 3-((6-amino-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl)benzonitrile (120 mg, 44.44%) as a yellow solid. MS (ESI): mass calcd. for C17H15N3O: 277.12 m / z, found 278.20 [M+H]+. 1-(tert-butyl)-3-(1-(3-cyanobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea To a solution of 3-((6-amino-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl)benzonitrile (80 mg, 0.288 mmol, 1 equiv) in DCM (5 mL) was added 2-isocyanato-2-methylpropane (85.8 mg, 0.865 mmol, 3 equiv) and TEA (87.4 mg, 0.865 mmol, 3 equiv). The resulting mixture was stirred for overnight at rt. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) & Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 25% B to 45% B in 10.5 min; Wave Length: 220 nm; RT1(min): 12; Number Of Runs: 1) to afford 1-(tert-butyl)-3-(1-(3-cyanobenzyl)-2-oxo-1,2,3,4- tetrahydroquinolin-6-yl)urea (47.9 mg, 44.35%) as a white solid. MS (ESI): mass calcd. for C22H24N4O: 376.19 m / z, found 377.10 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.12 (s, 1H), 7.67 – 7.75 (m, 2H), 7.48 – 7.58 (m, 2H), 7.33 (d, J = 2.4 Hz, 1H), 6.98 (dd, J = 8.8, 2.5 Hz, 1H), 6.74 (d, J = 8.8 Hz, 1H), 5.92 (s, 1H), 5.14 (s, 2H), 2.86 – 2.94 (m, 2H), 2.64 – 2.72 (m, 2H), 1.26 (s, 9H). Example 1: 3-tert-butyl-1-{1-[(2-fluorophenyl)methyl]-2-oxo-3,4-dihydroquinolin-6-yl}urea 1-[(2-fluorophenyl)methyl]-6-nitro-3,4-dihydroquinolin-2-one To a solution of 6-nitro-3,4-dihydro-1H-quinolin-2-one (2 g, 10.407 mmol, 1 equiv) and 1-(bromomethyl)-2-fluorobenzene (3147.60 mg, 16.651 mmol, 1.6 equiv) in dimethylformamide (20 mL) was added K2CO3 (4346.47 mg, 31.221 mmol, 3 equiv). The reaction was stirred at rt for 3h. Quenched with water (100 mL) and extracted with EA (3 x 100 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 1- [(2-fluorophenyl)methyl]-6-nitro-3,4-dihydroquinolin-2-one (2.06 g, 65.92%) as a white solid. MS (ESI): mass calcd. for C16H13FN2O3: 300.09 m / z, found 301.05[M+H]+. 6-amino-1-[(2-fluorophenyl)methyl]-3,4-dihydroquinolin-2-one To a solution of 1-[(2-fluorophenyl)methyl]-6-nitro-3,4-dihydroquinolin-2-one (1 g, 3.330 mmol, 1 equiv) in EA (35 mL) was added Pd / C (1 g). The resulting mixture was stirred for 1 h at room temperature under hydrogen atmosphere. Desired product could be detected by LCMS. The resulting mixture was filtered, the filter cake was washed with EA (3 x 10 mL). The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 6-amino-1-[(2-fluorophenyl)methyl]- 3,4-dihydroquinolin-2-one (990 mg, 109.98%) as a white solid. MS (ESI): mass calcd for C16H15FN2O: 270.12 m / z, found 271.10[M+H]+. 3-tert-butyl-1-{1-[(2-fluorophenyl)methyl]-2-oxo-3,4-dihydroquinolin-6-yl}urea To a solution of 6-amino-1-[(2-fluorophenyl)methyl]-3,4-dihydroquinolin-2-one (980 mg, 3.626 mmol, 1 equiv) in DCM / toluene (10 mL, 2 / 1) was added 2-isocyanato-2- methylpropane (1077.9 mg, 10.873 mmol, 3.00 equiv) The reaction was stirred at 90oC for 1h. Quenched with water (50 mL) and extracted with EA (3 x 50 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by preparative HPLC using aXBridge Prep OBD C18 Column 150 mm x 30 mm x 5 μm column (eluent: 17% to 42% (v / v) CH3CN and H2O with 10mmol / L NH4HCO3) to afford the title compound 3-tert-butyl-1-{1-[(2-fluorophenyl)methyl]-2-oxo-3,4-dihydroquinolin-6-yl}urea (412.3 mg, 30.33%) as a white solid. LC / MS (ESI): mass calcd. for C21H24FN3O2:369.19 m / z, found:370.05 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.13 (s, 1H), 7.35 (m, 1H), 7.23 - 7.32 (m, 2H), 7.00 -7.09(m, 3H), 6.73 (m, 1H), 5.93 (s, 1H), 5.12 (s, 2H), 2.89 (m, 2H), 2.66 (m, 2H), 1.27 (s, 9H).19F NMR (376 MHz, DMSO) δ-118.31. Example 20: 1-(tert-butyl)-3-(1-(2-cyanobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea 2-((6-nitro-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl)benzonitrile To a stirred solution of 6-nitro-3,4-dihydro-1H-quinolin-2-one (400 mg, 2.081 mmol, 1 equiv) in DMF (10 mL) was added 2-(bromomethyl)benzonitrile (612.09 mg, 3.122 mmol, 1.5 equiv) and potassium methaneperoxoate potassium (869.29 mg, 6.243 mmol, 3 equiv) at rt and stirred for overnight. The reaction progress was monitored by LCMS. The resulting mixture was extracted with brine (1 x 30 mL). The combined organic layers were washed with EA (3 x 30 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (3:1) to afford 2-[(6-nitro-2-oxo-3,4-dihydroquinolin-1-yl)methyl]benzonitrile (447 mg, 70.0%) as a yellow solid. MS (ESI): mass calcd. for C17H13N3O3: 307.10 m / z, found 308.10 [M +H]+. 2-((6-amino-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl)benzonitrile To a stirred solution of 2-[(6-nitro-2-oxo-3,4-dihydroquinolin-1-yl)methyl]benzonitrile (400 mg, 1.302 mmol, 1 equiv) in ethyl alcohol (10 mL) and water (2 mL) was added iron (726.89 mg, 13.020 mmol, 10 equiv) and NH4Cl (696.24 mg, 13.020 mmol, 10 equiv) and stirred for 1 h at 60 °C. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE / EA (2:1) to afford 2-((6- amino-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl)benzonitrile (280 mg, 77.57%) as a white solid. MS (ESI): mass calcd. for C17H15N3O: 277.12 m / z, found 278.05 [M +H]+. 1-(tert-butyl)-3-(1-(2-cyanobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea A solution of 2-((6-amino-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl)benzonitrile (150 mg, 0.541 mmol, 1 equiv) in DCM (5 mL) was add TEA (164.20 mg, 1.623 mmol, 3 equiv) and 2-isocyanato-2-methylpropane (214.48 mg, 2.164 mmol, 4 equiv) at 0 °C. The resulting mixture was stirred for 1 h at rt. The resulting mixture was concentrated under reduced pressure. The crude product was purified by HPLC with the following conditions (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 17% B to 42% B in 9 min, 42% B; Wave Length: 254 / 220 nm; RT1(min): 8.9; Number Of Runs: 0; to afford 3-tert-butyl-1-{1-[(2- cyanophenyl)methyl]-2-oxo-3,4-dihydroquinolin-6-yl}urea (69.2 mg, 33.91%) as a white solid. MS (ESI):mass calcd. for C22H24N4O2: 376.19 m / z, found 377.15 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.15 (s, 1H), 7.86 (dd, J = 7.7, 1.3 Hz, 1H), 7.61 (td, J = 7.7, 1.4 Hz, 1H), 7.44 (td, J = 7.6, 1.2 Hz, 1H), 7.37 (d, J = 2.4 Hz, 1H), 7.25 – 7.18 (m, 1H), 7.00 (dd, J = 8.7, 2.5 Hz, 1H), 6.69 (d, J = 8.8 Hz, 1H), 5.94 (s, 1H), 5.25 (s, 2H), 2.93 (dd, J = 8.7, 5.8 Hz, 2H), 2.67 (dd, J = 8.7, 5.8 Hz, 2H), 1.27 (s, 9H). Example 21: 1-(tert-butyl)-3-(1-(3-methylbenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6- yl)urea 6-amino-1-[(3-methylphenyl)methyl]-3,4-dihydroquinolin-2-one To a solution of 6-nitro-3,4-dihydro-1H-quinolin-2-one (500 mg, 2.602 mmol, 1 equiv) in DMF (8 mL) was added K2CO3 (1086.6 mg, 7.862 mmol, 3 equiv) and 1-(bromomethyl)-3- methylbenzene (529.6 mg, 2.862 mmol, 1.1 equiv). The resulting mixture was stirred for 16 h at rt. The mixture was diuted with EtOAc (100 mL), washed with water (3 x 50 mL), brine (2 x 50 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 1-[(3-methylphenyl)methyl]-6-nitro-3,4- dihydroquinolin-2-one (500 mg, 64.44%) as a yellow solid. MS (ESI): mass calcd. for C17H16N2O3296.12 m / z, found 297.00 [M+H]+. 6-amino-1-(1-phenylpropyl)-3,4-dihydroquinolin-2-one To a solution of 1-[(3-methylphenyl)methyl]-6-nitro-3,4-dihydroquinolin-2-one (500 mg, 1.687 mmol, 1 equiv) in EtOH (10 mL) and H2O (2.5 mL) was added Fe (942.2 mg, 16.873 mmol, 10 equiv) and NH4Cl (902.5 mg, 16.873 mmol, 10 equiv). The resulting mixture was stirred for 2 h at 60 °C. The mixture was diuted with EtOAc (100 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) to afford 6-amino-1-[(3- methylphenyl)methyl]-3,4-dihydroquinolin-2-one (400 mg, 88.46%) as a yellow solid. MS (ESI): mass calcd. for C17H18N2O 266.14 m / z, found 267.10 [M+H]+. 1-(tert-butyl)-3-(1-(3-methylbenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea To a solution of 6-amino-1-[(3-methylphenyl)methyl]-3,4-dihydroquinolin-2-one (400 mg, 1.502 mmol, 1 equiv) in DCM (10 mL) was added 2-isocyanato-2-methylpropane (446.6 mg, 4.506 mmol, 3 equiv) and TEA (455.9 mg, 4.505 mmol, 3 equiv). The resulting mixture was stirred for overnight at rt. The reaction mixture was quenched by water and extracted with EA (3 x 30 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column eluted with PE / EA (2:1) & Prep-HPLC (Column: XBridge Shield RP18 OBD Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 38% B to 60% B in 10 min, 60% B; Wave Length: 254 / 220 nm; RT1(min): 10; Number Of Runs: 0) to afford 1-(tert-butyl)-3-(1-(3-methylbenzyl)- 2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea (282.3 mg, 51.15%) as a white solid. MS (ESI): mass calcd. for C22H27N3O2, 365.21 m / z, found 366.05 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.11 (s, 1H), 7.33 (d, J = 2.4 Hz, 1H), 7.17 (t, J = 7.7 Hz, 1H), 6.92 – 7.09 (m, 4H), 6.76 (d, J = 8.8 Hz, 1H), 5.92 (s, 1H), 5.05 (s, 2H), 2.87 (dd, J = 8.8, 5.8 Hz, 2H), 2.64 (dd, J = 8.7, 5.8 Hz, 2H), 2.25 (s, 3H), 1.27 (s, 9H). Example 22: 1-(tert-butyl)-3-(1-(3-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6- 1-[(3-methoxyphenyl)methyl]-6-nitro-3,4-dihydroquinolin-2-one To a solution of 6-nitro-3,4-dihydro-1H-quinolin-2-one (500 mg, 2.602 mmol, 1 equiv) in DMF (8 mL) was added K2CO3(1078.7 mg, 7.862 mmol, 3 equiv) and 1-(bromomethyl)-3- methoxybenzene (575.4 mg, 2.862 mmol, 1.1 equiv). The resulting mixture was stirred for 16 h at rt. The mixture was diuted with EtOAc (100 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 1-[(3-methoxyphenyl)methyl]-6-nitro-3,4- dihydroquinolin-2-one (500 mg, 60.71%) as a yellow solid. MS (ESI): mass calcd. for C17H16N2O4312.11 m / z, found 313.05 [M+H]+.

[0008] 6-amino-1-(1-phenylpropyl)-3,4-dihydroquinolin-2-one To a solution of 1-[(3-methoxyphenyl)methyl]-6-nitro-3,4-dihydroquinolin-2-one (500 mg, 1.601 mmol, 1 equiv) in EtOH (10 mL) and H2O (2.5 mL) was added Fe (894.0 mg, 16.009 mmol, 10 equiv) and NH4Cl (856.3 mg, 16.009 mmol, 10 equiv). The resulting mixture was stirred for 2 h at 60 °C. The mixture was diuted with EtOAc (100 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) to afford 6-amino-1-[(3- methoxyphenyl)methyl]-3,4-dihydroquinolin-2-one (400 mg, 88.33%) as a yellow solid. MS (ESI): mass calcd. for C17H18N2O2282.14 m / z, found 283.10 [M+H]+. 1-(tert-butyl)-3-(1-(3-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea To a solution of 6-amino-1-[(3-methoxyphenyl)methyl]-3,4-dihydroquinolin-2-one (400 mg, 1.417 mmol, 1 equiv) in DCM (10 mL) was added 2-isocyanato-2-methylpropane (421.3 mg, 4.250 mmol, 3 equiv) and TEA (430.0 mg, 4.250 mmol, 3 equiv). The resulting mixture was stirred for overnight at rt. The reaction mixture was quenched by water and extracted with EA (3 x 30 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column eluted with PE / EA (2:1) & Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 26% B to 50% B in 9 min, 50% B; Wave Length: 254 / 220 nm; RT1(min): 8.6; Number Of Runs: 0) to afford 1-(tert-butyl)-3-(1-(3- methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea (85.3 mg, 15.75%) as a white solid. MS (ESI): mass calcd. for C22H27N3O3, 381.21 m / z, found 382.15 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.11 (s, 1H), 7.33 (d, J = 2.4 Hz, 1H), 7.16 – 7.25 (m, 1H), 6.97 (dd, J = 8.7, 2.5 Hz, 1H), 6.71 – 6.82 (m, 4H), 5.92 (s, 1H), 5.06 (s, 2H), 3.70 (s, 3H), 2.87 (dd, J = 8.8, 5.8 Hz, 2H), 2.64 (dd, J = 8.7, 5.8 Hz, 2H), 1.26 (s, 9H). Example 23: 1-(tert-butyl)-3-(2-oxo-1-(3-(trifluoromethyl)benzyl)-1,2,3,4- tetrahydroquinolin-6-yl)urea 6-nitro-1-(3-(trifluoromethyl)benzyl)-3,4-dihydroquinolin-2(1H)-one To a solution of 6-nitro-3,4-dihydro-1H-quinolin-2-one (500 mg, 2.602 mmol, 1 equiv) in DMF (8 mL) was added K2CO3 (1086.6 mg, 7.862 mmol, 3 equiv) and 1-(bromomethyl)-3- (trifluoromethyl)benzene (684.1 mg, 2.862 mmol, 1.1 equiv). The resulting mixture was placed at rt and stirred overnight until the starting material was totally consumed by LCMS, The mixture was diuted with EtOAc (100 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by flash chromatography (PE / EA=3:1r) to afford 6-nitro-1-{[3-(trifluoromethyl)phenyl]methyl}-3,4- dihydroquinolin-2-one (500 mg, 54.86%) as a yellow solid. MS (ESI): mass calcd. for C17H13F3N2O3350.09 m / z, found 350.95 [M+H]+. 6-amino-1-(3-(trifluoromethyl)benzyl)-3,4-dihydroquinolin-2(1H)-one To a solution of 6-nitro-1-{[3-(trifluoromethyl)phenyl]methyl}-3,4-dihydroquinolin-2-one (500 mg, 1.427 mmol, 1 equiv) in EtOH (10 mL) and H2O (2.5 mL) was added Fe (797.1 mg, 14.274 mmol, 10 equiv) and NH4Cl (763.4 mg, 14.274 mmol, 10 equiv). The resulting mixture was stirred 30 min at 60 °C until the starting material was totally consumed by LCMS, The mixture was diuted with EtOAc (100 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by flash chromatography (PE / EA=2:1) to afford 6-amino-1-{[3-(trifluoromethyl)phenyl]methyl}-3,4- dihydroquinolin-2-one (300 mg, 64.88%) as a yellow solid.MS (ESI): mass calcd. for C17H15F3N2O 320.11 m / z, found 321.05 [M+H]+. 1-(tert-butyl)-3-(2-oxo-1-(3-(trifluoromethyl)benzyl)-1,2,3,4-tetrahydroquinolin-6-yl)urea To a solution of 6-amino-1-{[3-(trifluoromethyl)phenyl]methyl}-3,4-dihydroquinolin-2- one (300 mg, 0.937 mmol, 1 equiv) in DCM (10 mL) was added 2-isocyanato-2-methylpropane (278.5 mg, 2.810 mmol, 3 equiv) and TEA (284.3 mg, 2.810 mmol, 3 equiv).The resulting mixture was stirred for overnight at rt. The reaction mixture was quenched by water and extracted with EA (3*20 mL).The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by flash chromatography (0-100% ethyl acetate / petroleum ether) to afford 100 mg crude product as a white solid.The compound was separated by preparative HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 26% B to 45% B in 10 min, 45% B; Wave Length: 254 / 220 nm; RT1(min): 8.9; Number Of Runs: 0) to afford 3- tert-butyl-1-(2-oxo-1-{[3-(trifluoromethyl)phenyl]methyl}-3,4-dihydroquinolin-6-yl)urea (125.4 mg, 31.80%) as a white solid. MS (ESI): mass calcd. for C22H24F3N3O2, 419.18 m / z, found 419.95 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.13 (s, 1H), 7.45 – 7.63 (m, 4H), 7.34 (d, J = 2.4 Hz, 1H), 7.00 (dd, J = 8.7, 2.5 Hz, 1H), 6.80 (d, J = 8.8 Hz, 1H), 5.93 (s, 1H), 5.20 (s, 2H), 2.89 (dd, J = 8.8, 5.7 Hz, 2H), 2.67 (dd, J = 8.6, 5.8 Hz, 2H), 1.27 (s, 9H). Example 24: 3-tert-butyl-1-{1-[(2,5-dichlorophenyl)methyl]-2-oxo-3,4-dihydroquinolin-6- yl}urea 1-[(2,5-dichlorophenyl)methyl]-6-nitro-3,4-dihydroquinolin-2-one To a stirred solution of 6-nitro-3,4-dihydro-1H-quinolin-2-one (500 mg, 2.602 mmol, 1 equiv) in DMF (10 mL) was added 2-(bromomethyl)-1,4-dichlorobenzene (936.34 mg, 3.903 mmol, 1.5 equiv) and potassium carbonate (724.41 mg, 5.204 mmol, 2 equiv) at room temperature under nitrogen atmosphere. The final reaction mixture was stirred for 3 h at room temperature. The reaction was monitored by LCMS. The resulting mixture was quenched with water (20 mL) and extracted with EA (3 x 30 mL). The combined organic layers were washed with brine (2 x 30 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 1-[(2,5-dichlorophenyl)methyl]-6-nitro-3,4- dihydroquinolin-2-one (500 mg, 54.72%) as a white solid. LC / MS: mass calcd. for C16H12Cl2N2O3: 350.02 m / z, found:350.90 [M+H]+ 6-amino-1-[(2,5-dichlorophenyl)methyl]-3,4-dihydroquinolin-2-one To a stirred solution of 1-[(2,5-dichlorophenyl)methyl]-6-nitro-3,4-dihydroquinolin-2-one (500 mg, 1.424 mmol, 1 equiv) in EtOH / H2O (10 mL, 10 / 1) was added Fe (795.11 mg, 14.240 mmol, 10 equiv) and NH4Cl (761.58 mg, 14.240 mmol, 10 equiv) at room temperature under nitrogen atmosphere. The final reaction mixture was stirred for 2 h at 60°C. The reaction was quenched with water at rt. After filtration, the filter cake was washed with EA (3 x 20 mL). The filtrate was added water (20 mL) and extracted with EA (3 x 20 mL). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 6-amino-1-[(2,5-dichlorophenyl)methyl]-3,4- dihydroquinolin-2-one (280 mg, 61.23%) as a white solid. LC / MS: mass calcd. for C16H14Cl2N2O: 320.05 m / z, found:320.95 [M+H]+. 3-tert-butyl-1-{1-[(2,5-dichlorophenyl)methyl]-2-oxo-3,4-dihydroquinolin-6-yl}urea To a stirred solution of 6-amino-1-[(2,5-dichlorophenyl)methyl]-3,4-dihydroquinolin-2- one (140 mg, 0.436 mmol, 1 equiv) and 2-isocyanato-2-methylpropane (129.63 mg, 1.308 mmol, 3 equiv) in DCM (10 mL) was added TEA (132.32 mg, 1.308 mmol, 3 equiv) dropwise at 0°C under nitrogen atmosphere. The resulting mixture was stirred for 1 day at room temperature under nitrogen atmosphere. The reaction was monitored by LCMS. Quenched with water (10 mL) and extracted with EA (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The crude product was purified by Prep-HPLC to afford 3-tert-butyl-1-{1-[(2,5-dichlorophenyl)methyl]-2-oxo-3,4-dihydroquinolin-6-yl}urea (20.8 mg, 11.34%) as a white solid. LC / MS: mass calcd for C21H23Cl2N3O2: 419.12 m / z, found:420.05 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.16 (s, 1H), 7.56 (d, J = 8.4 Hz, 1H), 7.40 - 7.37 (m, 2H), 7.01 - 6.95 (m, 2H), 6.60 (d, J = 8.4 Hz, 1H), 5.94 (s, 1H), 5.05 (s, 2H), 2.94 - 2.90 (m, 2H), 2.72 - 2.69 (m, 2H), 1.27 (s, 9H). Example 25: 1-(tert-butyl)-3-(1-(3,5-dichlorobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) urea

[0009] 1-(3,5-dichlorobenzyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one To a mixture of 6-nitro-3,4-dihydro-1H-quinolin-2-one (400 mg, 2.081 mmol, 1 equiv) and K2CO3(869.29 mg, 6.243 mmol, 3 equiv) in DMF (20 mL) was added 1-(bromomethyl)-3,5- dichlorobenzene (749.07 mg, 3.122 mmol, 1.5 equiv). The reaction was stirred at rt for 2 hours. Quenched with water (30 mL) and extracted with EA (3 x 30 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 1-[(3,5- dichlorophenyl)methyl]-6-nitro-3,4-dihydroquinolin-2-one (647 mg, 88.51%) as a yellow solid. MS (ESI): mass calcd. for C16H12Cl2N2O3: 351.18m / z, found 350.95 [M+H]+. 6-amino-1-(3,5-dichlorobenzyl)-3,4-dihydroquinolin-2(1H)-one To a solution of 1-[(3,5-dichlorophenyl)methyl]-6-nitro-3,4-dihydroquinolin-2-one (500 mg, 1.424 mmol, 1 equiv) in MeOH / H2O (11 mL, 10 / 1) was added Fe (397.55 mg, 7.120 mmol, 5 equiv) and NH4Cl (380.79 mg, 7.120 mmol, 5 equiv). The reaction was stirred at 80oC for 1 hours. After filtration, the filter cake was washed with EA (3 x 10 mL). The filtrate was added water (20 mL) and extracted with EA (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The resulting mixture was concentrated under vacuum. This resulted in 6-amino-1-[(3,5-dichlorophenyl)methyl]-3,4- dihydroquinolin-2-one (418 mg, 91.40%) as a yellow solid. MS (ESI): mass calcd. for C16H14Cl2N2O: 321.20 m / z, found 320.95 [M+H]+.

[0010] 1-(tert-butyl)-3-(1-(3,5-dichlorobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea To a solution of 6-amino-1-[(3,5-dichlorophenyl)methyl]-3,4-dihydroquinolin-2-one (100 mg, 0.311 mmol, 1 equiv) in DCM (10 mL) was added 2-isocyanato-2-methylpropane (92.59 mg, 0.933 mmol, 3 equiv) and TEA (94.51 mg, 0.933 mmol, 3 equiv) at 0oC. The reaction was stirred at rt for 2 days. Quenched with water (20 mL) and extracted with EA (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by preparative HPLC using a XBridge Shield RP18 OBD Column, 30*150 mm, 5μm column (eluent: 45% to 67% (v / v) CH3CN and H2O with 10mmol / L NH4HCO3) to afford the title compound 3-tert-butyl-1-{1-[(3,5-dichlorophenyl)methyl]-2-oxo- 3,4-dihydroquinolin-6-yl}urea (20 mg, 15.28%) as a white solid. MS (ESI): mass calcd. for C21H23Cl2N3O2:420.33 m / z, found:420.15 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.04 – 8.23 (m, 1H), 7.39 – 7.49 (m, 1H), 7.22 – 7.39 (m, 3H), 6.94 – 7.11 (m, 1H), 6.65 – 6.88 (m, 1H), 5.80 – 6.01 (m, 1H), 5.00 – 5.21 (m, 2H), 2.81 – 2.98 (m, 2H), 2.60 – 2.78 (m, 2H), 1.25 – 1.33 (m, 9H). Example 26: 1-(tert-butyl)-3-(1-(3-fluorobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea 1-(3-fluorobenzyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one To a solution of 6-nitro-3,4-dihydro-1H-quinolin-2-one (500 mg, 2.602 mmol, 1 equiv) in DMF (20 mL) was added K2CO3 (1086.62 mg, 7.806 mmol, 3 equiv) and (bromomethyl)-3- fluorobenzene (737.72 mg, 3.903 mmol, 1.5 equiv) at rt. The final reaction mixture was stirred for 1h at rt. Quenched with water (20 mL) and extracted with EA (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 1- [(3-fluorophenyl)methyl]-6-nitro-3,4-dihydroquinolin-2-one (163 mg, 20.86%) as a yellow solid. MS (ESI): mass calcd. for C16H13FN2O3: 300.29 m / z, found 301.00 [M+H]+. 6-amino-1-(3-fluorobenzyl)-3,4-dihydroquinolin-2(1H)-one To a solution of 1-[(3-fluorophenyl)methyl]-6-nitro-3,4-dihydroquinolin-2-one (155 mg, 0.516 mmol, 1 equiv) in MeOH / H2O (22 mL, 10 / 1) was added Fe (144.13 mg, 2.580 mmol, 5 equiv) and NH4Cl (138.05 mg, 2.580 mmol, 5 equiv). The reaction was stirred at 80 °C for 1 hour. The resulting mixture was filtered, the filter cake was washed with EA (3 x 20 mL). The filtrate was concentrated under reduced pressure. The residue was added water (20 mL) and extracted with EA (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 6-amino-1-[(3-fluorophenyl)methyl]-3,4- dihydroquinolin-2-one hydrochloride (100 mg, 63.15%) as a yellow oil. MS (ESI): mass calcd. for C16H15FN2O: 270.31m / z, found 271.15 [M+H]+. 1-(tert-butyl)-3-(1-(3-fluorobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea To a solution of 6-amino-1-[(3-fluorophenyl)methyl]-3,4-dihydroquinolin-2-one (90 mg, 0.333 mmol, 1 equiv) in DCM (10 mL) was added 2-isocyanato-2-methylpropane (99.02 mg, 0.999 mmol, 3 equiv) and Pyridine (79.01 mg, 0.999 mmol, 3 equiv). The reaction was stirred at rt for 3 days. Quenched with water (20 mL) and extracted with DCM (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by preparative HPLC using a XBridge Prep OBD C18 Column, 30*150 mm, 5μm column (eluent: 17% to 42% (v / v) CH3CN and H2O with 10mmol / L NH4HCO3) to afford the title compound 3-tert-butyl-1-{1-[(3-fluorophenyl)methyl]-2-oxo-3,4-dihydroquinolin- 6-yl}urea (20.7 mg, 16.83%) as a white solid. MS (ESI): mass calcd. for C21H24FN3O2:369.44 m / z, found:370.15 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 7.96 – 8.19 (m, 1H), 7.30 – 7.40 (m, 2H), 6.93 – 7.19 (m, 4H), 6.69 – 6.81 (m, 1H), 5.80 – 6.00 (m, 1H), 4.98 – 5.29 (m, 2H), 2.81 – 2.94 (m, 2H), 2.60 – 2.71 (m, 2H), 1.19 – 1.29 (m, 9H).19F NMR (376 MHz, DMSO) δ (ppm): -113.2050. Example 27: 1-(tert-butyl)-3-(1-(4-fluorobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea 1-(4-fluorobenzyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one To a solution of 6-nitro-3,4-dihydro-1H-quinolin-2-one (500 mg, 2.602 mmol, 1 equiv) and K2CO3 (1086.62 mg, 7.806 mmol, 3 equiv) in DMF (10 mL) was added 1-(bromomethyl)-4- fluorobenzene (737.78 mg, 3.903 mmol, 1.5 equiv). The reaction was stirred at rt for 2 hours. Quenched with water (20 mL) and extracted with EA (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 1-[(4- fluorophenyl)methyl]-6-nitro-3,4-dihydroquinolin-2-one (630 mg, 80.64%) as a yellow solid. MS(ESI): mass calcd. for C16H13FN2O3: 300.29 m / z, found 301.00 [M+H]+. 6-amino-1-(4-fluorobenzyl)-3,4-dihydroquinolin-2(1H)-one To a solution of 1-[(4-fluorophenyl)methyl]-6-nitro-3,4-dihydroquinolin-2-one (400 mg, 1.332 mmol, 1 equiv) in MeOH / H2O (22 mL, 10 / 1) was added Fe (371.94 mg, 6.660 mmol, 5 equiv) and NH4Cl (356.26 mg, 6.660 mmol, 5 equiv). The reaction was stirred for 1 hour at 80oC. The reaction was quenched with water at rt. After filtration, the filter cake was washed with EA (3 x 20 mL). The filtrate was added water (20 mL) and extracted with EA (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The resulting mixture was concentrated under vacuum. This resulted in 6-amino-1-[(4- fluorophenyl)methyl]-3,4-dihydroquinolin-2-one (325 mg, 90.26%) as a yellow solid. MS (ESI): mass calcd. for C16H15FN2O: 270.31m / z, found 271.05 [M+H]+. 1-(tert-butyl)-3-(1-(4-fluorobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea To a solution of 6-amino-1-[(4-fluorophenyl)methyl]-3,4-dihydroquinolin-2-one (150 mg, 0.555 mmol, 1 equiv) in DCM (20 mL) was added 2-isocyanato-2-methylpropane (165.03 mg, 1.665 mmol, 3 equiv) and Pyridine (131.68 mg, 1.665 mmol, 3 equiv). The reaction was stirred at rt for 3 days. Quenched with water (10 mL) and extracted with EA (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by preparative HPLC using a XBridge Prep OBD C18 Column, 30*150 mm, 5μm column (eluent: 17% to 42% (v / v) CH3CN and H2O with 10mmol / L NH4HCO3) to afford the title compound 3-tert-butyl-1-{1-[(4-fluorophenyl)methyl]-2-oxo-3,4-dihydroquinolin- 6-yl}urea (5.3 mg, 2.59%) as a white solid. MS (ESI): mass calcd. for C21H24FN3O2:369.44 m / z, found:370.15 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 7.11 – 7.40 (m, 3H), 6.96 – 7.11 (m, 3H), 6.81– 6.91 (m, 1H), 5.10– 5.22 (m, 2H), 2.82 – 3.03 (m, 2H), 2.59 – 2.82 (m, 2H), 1.29 – 1.41 (m, 9H).19F NMR (376 MHz, DMSO) δ (ppm): -117.9957. Example 28: 1-(tert-butyl)-3-(2-oxo-1-(1-phenylpropyl)-1,2,3,4-tetrahydroquinolin-6- yl)urea 6-nitro-1-(1-phenylpropyl)-3,4-dihydroquinolin-2-one To a solution of 6-nitro-3,4-dihydro-1H-quinolin-2-one (400 mg, 2.081 mmol, 1 equiv) in DMF (8 mL) was added K2CO3 (863.0 mg, 6.244 mmol, 3 equiv) and (1-bromopropyl)benzene (455.8 mg, 2.289 mmol, 1.1 equiv). The resulting mixture was stirred for 16 h at rt. The mixture was diuted with EtOAc (100 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 6-nitro-1-(1-phenylpropyl)-3,4-dihydroquinolin-2- one (150 mg, 22.24%) as a yellow solid. MS (ESI): mass calcd. for C18H18N2O3310.13 m / z, found 311.25 [M+H]+. 6-amino-1-(1-phenylpropyl)-3,4-dihydroquinolin-2-one To a solution of 6-nitro-1-(1-phenylpropyl)-3,4-dihydroquinolin-2-one (130 mg, 0.419 mmol, 1 equiv) in EtOH (8 mL) and H2O (2 mL) was added Fe (233.9 mg, 4.189 mmol, 10 equiv) and NH4Cl (224.0 mg, 4.189 mmol, 10 equiv). The resulting mixture was stirred for 2 h at 60 °C. The mixture was diuted with EtOAc (100 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (2:1) to afford 6-amino-1-(1-phenylpropyl)-3,4- dihydroquinolin-2-one (100 mg, 85.15%) as a yellow solid.MS (ESI): mass calcd. for C18H20N2O 280.16 m / z, found 281.10 [M+H]+. 1-(tert-butyl)-3-(2-oxo-1-(1-phenylpropyl)-1,2,3,4-tetrahydroquinolin-6-yl)urea To a solution of 6-amino-1-(1-phenylpropyl)-3,4-dihydroquinolin-2-one (100 mg, 1.502 mmol, 1 equiv) in DCM (8 mL) was added 2-isocyanato-2-methylpropane (106.0 mg, 1.070 mmol, 3 equiv) and TEA (108.2 mg, 1.070 mmol, 3 equiv). The resulting mixture was stirred for overnight at rt. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column eluted with PE / EA (2:1) & Prep-HPLC (Column: Aeris PEPTIDE 5um XB-C18 Axia, 21.2 mm X 250 mm, 5 μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 39% B to 61% B in 10.5 min; Wave Length: 220 nm; RT1(min): 7.9; Number Of Runs: 2) to afford 1-(tert-butyl)-3-(2-oxo-1-(1-phenylpropyl)-1,2,3,4- tetrahydroquinolin-6-yl)urea (29.8 mg, 21.98%) as a white solid. MS (ESI): mass calcd. for C23H29N3O2, 379.23 m / z, found 380.20 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.09 (s, 1H), 7.20 – 7.41 (m, 6H), 6.81 (dd, J = 8.8, 2.5 Hz, 1H), 6.49 (d, J = 8.8 Hz, 1H), 5.95 (d, J = 13.1 Hz, 2H), 2.74 – 2.92 (m, 2H), 2.56 – 2.74 (m, 2H), 2.31 – 2.40 (m, 1H), 2.04 – 2.22 (m, 1H), 1.25 (s, 9H), 0.77 (t, J = 7.2 Hz, 3H). Example 29: 1-(1-benzyl-3,3-dimethyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(tert- butyl)urea Synthetic Scheme

[0011] N-(2-bromophenyl)pivalamide To a stirred solution of O-bromoaniline (3 g, 17.439 mmol, 1 equiv) in anhydrous DCM (50 mL) was added triethylamine (2.29 g, 22.671 mmol, 1.3 equiv) followed by 2,2- dimethylpropanoyl chloride (2.10 g, 17.439 mmol, 1 equiv) at 0 °C. The reaction mixture was stirred for 16 h at rt. After completion of reaction, the reaction mixture was quenched by addition of water (50 mL). The aqueous layer was extracted with DCM (50 mL). The combined organic phase was washed with brine (30 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product which was further purified by silica gel column, eluted with PE / EA (3:1) to afford desired compound N-(2-bromophenyl)-2,2- dimethylpropanamide (2.7 g, 60.44%) as a yellow solid. MS (ESI): mass calcd. for C11H14BrNO: 255.03 m / z, found 256.05 [M +H]+. 3,3-dimethyl-3,4-dihydroquinolin-2(1H)-one To a stirred solution of N-(2-bromophenyl)-2,2-dimethylpropanamide (400 mg, 1.562 mmol, 1 equiv) in NMP (20 mL, 207.398 mmol, 132.81 equiv) was added Cs2CO3(1.02 g, 3.124 mmol, 2 equiv), tris(4-methylphenyl)phosphane (95.06 mg, 0.312 mmol, 0.2 equiv), Pd(OAc)2(35.06 mg, 0.156 mmol, 0.1 equiv) and TBHP (42.22 mg, 0.469 mmol, 0.3 equiv) at rt and stirred for overnight at 140 °C under N2. The reaction mixture was concentrated under reduced pressure to give crude product which was further purified by silica, gel column PE / EA (3:1) to afford desired compound 3,3-dimethyl-1,4-dihydroquinolin-2-one (0.2 g, 73.26%). MS (ESI): mass calcd. for C11H13NO: 175.10 m / z, found 176.25 [M +H]+. 3,3-dimethyl-6-nitro-3,4-dihydroquinolin-2(1H)-one To a solution of 3,3-dimethyl-3,4-dihydroquinolin-2(1H)-one (0.2 g, 1.14 mmol, 1 equiv) in H2O (2 mL) and H2SO4(9 mL) was added HNO3(0.2 mL) at -10 °C. The reaction was stirred for 2 h at -10-0 °C. The reaction mixture was quenched by water. The mixture was acidified pH = 7 with NaHCO3 (aq.) and then extracted with EA (3 x 50 mL). The combined organic extracts were washed with brine (50 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 3,3-dimethyl-6-nitro-3,4-dihydroquinolin-2(1H)-one (0.15 g, 60.0%) as a white solid. MS (ESI): mass calcd. for C11H12N2O3, 220.08 m / z, found 221.05 [M+H]+ . 1-benzyl-3,3-dimethyl-6-nitro-3,4-dihydroquinolin-2(1H)-one To a stirred solution of 3,3-dimethyl-6-nitro-1,4-dihydroquinolin-2-one (150 mg, 0.681 mmol, 1 equiv) in DMF (3 mL) was added K2CO3(322.39 mg, 2.316 mmol, 3 equiv) and benzyl bromide (158.43 mg, 0.926 mmol, 1.2 equiv) at rt and stirred for overnight. The resulting mixture was extracted with EA (3 x 30 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 1-benzyl-3,3-dimethyl-6-nitro- 3,4-dihydroquinolin-2(1H)-one (150 mg, 71.09%) as a white solid. MS (ESI): mass calcd. for C18H18N2O3: 310.13 m / z, found 311.10 [M +H]+. 6-amino-1-benzyl-3,3-dimethyl-3,4-dihydroquinolin-2(1H)-one To a solution of 1-benzyl-3,3-dimethyl-6-nitro-3,4-dihydroquinolin-2(1H)-one (130 mg, 0.419 mmol, 1 equiv) in 10 mL MeOH was added Pd / C (30 mg) under nitrogen atmosphere. The mixture was hydrogenated at room temperature for 50 min under hydrogen atmosphere using a hydrogen balloon, then filtered through a Celite pad and concentrated under reduced pressure to afford 6-amino-1-benzyl-3,3-dimethyl-4H-quinolin-2-one (100 mg, 85.15%) as a white solid. MS (ESI): mass calcd. for C18H20N2O: 280.16 m / z, found 281.25 [M +H]+. 1-(1-benzyl-3,3-dimethyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(tert-butyl)urea To a stirred solution of 6-amino-1-benzyl-3,3-dimethyl-4H-quinolin-2-one (50 mg, 0.178 mmol, 1 equiv) in anhydrous DCM (5 mL) was added TEA (54.14 mg, 0.534 mmol, 3 equiv) 2- isocyanato-2-methylpropane (70.72 mg, 0.712 mmol, 4 equiv) at 0 °C, and stirred for overnight at rt. After completion of reaction, the reaction mixture was concentrated under reduced pressure to give crude product which was further purified by HPLC with the following conditions Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 44% B to 60% B in 8.5 min; Wave Length: 220 nm; RT1(min): 6.9; Number Of Runs: 3; to afford 1-(1-benzyl- 3,3-dimethyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(tert-butyl)urea (5.6 mg, 8.26%) as a white solid. MS (ESI):mass calcd. for C23H29N3O2: 379.23 m / z, found 380.20 [M+H]+.1H NMR (300 MHz, Methanol-d4) δ 7.18 – 7.34 (m, 6H), 7.01 – 7.04 (m, 1H), 6.82 (d, J = 8.7 Hz, 1H), 5.16 (s, 2H), 2.84 (s, 2H), 1.36 (s, 9H), 1.23 (s, 6H). Example 30: 1-(tert-butyl)-3-(1-(2-hydroxy-1-phenylethyl)-2-oxo-1,2,3,4-tetrahydroquinoli n-6-yl)urea Synthetic Scheme Into a 40 mL round-bottom flask was added 2-bromo-2-phenylethan-1-ol (3 g, 21.713 mmol, 1 equiv) and bromotrimethylsilane (3.66 g, 23.884 mmol, 1.1 equiv) at rt. The resulting mixture was stirred for additional overnight at rt. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (5:1) afford 2-bromo-2-phenylethanol (2.7 g, 61.85%) as a yellow semi-solid. (2-bromo-2-phenylethoxy)(tert-butyl)dimethylsilane To a stirred solution of 2-bromo-2-phenylethanol (1.4 g, 6.963 mmol, 1 equiv) in anhydrous DCM (30 mL) was added t-butyldimethylchlorosilane (2.10 g, 13.926 mmol, 2 equiv) and Imidazole (1.42 g, 20.889 mmol, 3 equiv) at rt and stirred for 1 h. The reaction progress was monitored by TLC. The residue was purified by silica gel column chromatography, eluted with EA (35%-58%) to afford (2-bromo-2-phenylethoxy)(tert-butyl)dimethylsilane (1.2 g, 54.65%) as a yellow semi-solid. 1-(2-((tert-butyldimethylsilyl)oxy)-1-phenylethyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one To a stirred solution of (2-bromo-2-phenylethoxy)(tert-butyl)dimethylsilane (500 mg, 1.586 mmol, 1 equiv) in dimethylformamide (10 mL) was added 6-nitro-3,4-dihydro-1H- quinolin-2-one (274.25 mg, 1.427 mmol, 0.9 equiv) and Cs2CO3(1549.92 mg, 4.758 mmol, 3 equiv) at rt and stirred for overnight. The reaction progress was monitored by LCMS. The resulting mixture was extracted with EA (3 x 30 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (3:1) to afford 1-(2-((tert- butyldimethylsilyl)oxy)-1-phenylethyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one (350 mg, 51.74%) as a yellow solid. MS (ESI): mass calcd. for C23H30N2O4Si: 426.20 m / z, found 427.15 [M +H]+. 6-amino-1-(2-((tert-butyldimethylsilyl)oxy)-1-phenylethyl)-3,4-dihydroquinolin-2(1H)-one To a solution of 1-(2-((tert-butyldimethylsilyl)oxy)-1-phenylethyl)-6-nitro-3,4- dihydroquinolin-2(1H)-one (80 mg, 0.188 mmol, 1 equiv) in 10 mL MeOH was added Pd / C (10%, 50 mg) under nitrogen atmosphere in a 50 mL. The mixture was hydrogenated at room temperature for 1 h under hydrogen atmosphere using a hydrogen balloon, filtered through a Celite pad and concentrated under reduced pressure to afford 6-amino-1-(2-((tert- butyldimethylsilyl)oxy)-1-phenylethyl)-3,4-dihydroquinolin-2(1H)-one (75 mg, 100.0%) as a white solid. MS (ESI): mass calcd. for C23H32N2O2S: 396.22 m / z, found 397.30 [M +H]+. 1-(tert-butyl)-3-(1-(2-((tert-butyldimethylsilyl)oxy)-1-phenylethyl)-2-oxo-1,2,3,4- tetrahydroquinolin-6-yl)urea o a stirred solution of 6-amino-1-(2-((tert-butyldimethylsilyl)oxy)-1-phenylethyl)-3,4- dihydroquinolin-2(1H)-one (100 mg, 0.252 mmol, 1 equiv) in DCM (10 mL) was added 2- isocyanato-2-methylpropane (74.99 mg, 0.756 mmol, 3 equiv) and toluene (5 mL, 46.993 mmol, 186.38 equiv) at rt and stirred for overnight at 90 °C. The reaction progress was monitored by LCMS. After completion of reaction, the reaction mixture was concentrated under reduced pressure to give crude product. MS (ESI): mass calcd. for C28H41N3O3Si: 495.29 m / z, found 496.30 [M +H]+. 1-(tert-butyl)-3-(1-(2-hydroxy-1-phenylethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea To a stirred solution of 1-(tert-butyl)-3-(1-(2-((tert-butyldimethylsilyl)oxy)-1- phenylethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea (crude) in tetrahydrofuran (5 mL) was added Triethylamine trihydrofluoride (300 mg) and stirred for 2 h at 60 °C. The reaction progress was monitored by LCMS. After completion of reaction, the reaction mixture was concentrated under reduced pressure to give crude product which was further purified by HPLC with the following conditions Column: Xselect CSH F-Phenyl OBD column, 19*250 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 25 mL / min; Gradient: 45% B to 75% B in 7 min, 75% B; Wave Length: 254 / 220 nm; RT1(min): 6.4; Number Of Runs: 0 to afford 3-tert-butyl-1-[1-(2-hydroxy-1-phenylethyl)-2-oxo-3,4- dihydroquinolin-6-yl]urea (4 mg, 10.30%) as a white solid. MS (ESI):mass calcd. for C22H27N3O3: 381.21 m / z, found 382.20 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.09 (s, 1H), 7.33 (d, J = 4.0 Hz, 5H), 7.25 (q, J = 4.2 Hz, 1H), 6.87 (dd, J = 8.8, 2.5 Hz, 1H), 6.60 (d, J = 8.8 Hz, 1H), 5.89 (d, J = 13.5 Hz, 1H), 5.71 (d, J = 7.1 Hz, 1H), 5.01 (t, J = 5.5 Hz, 1H), 4.26 (dt, J = 11.4, 6.0 Hz, 1H), 4.07 (dt, J = 11.1, 6.1 Hz, 1H), 2.93 – 2.77 (m, 2H), 2.58 (q, J = 6.5 Hz, 2H), 1.26 (s, 9H). Example 31: 1-(1-benzyl-2-oxo-3H-indol-5-yl)-3-tert-butylurea Synthetic Scheme 1-benzyl-5-nitroindole-2,3-dione To a solution of 1H-indole-2,3-dione, 5-nitro (1 g, 5.205 mmol, 1 equiv) and benzyl bromide (979.24 mg, 5.726 mmol, 1.1 equiv) in dimethylformamide (10 mL) was added K2CO3 (1438.66 mg, 10.41 mmol, 2 equiv). The reaction was stirred at rt for 3h. Quenched with water (40 mL) and extracted with EA (3 x 40 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 1-benzyl-5-nitroindole-2,3-dione (665 mg, 45.27%) as a white solid. MS (ESI): mass calcd for C15H10N2O4: 282.06 m / z, found 283.15[M+H]+. benzyl-5-nitro-3H-indol-2-one To a solution of 1-benzyl-5-nitroindole-2,3-dione (500 mg, 1.771 mmol, 1 equiv) in Hydrazinium hydroxide solution (5 mL) was stirred at 120 °C for 3h. Quenched with water (20 mL) and extracted with EA (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to 1-benzyl-5-nitro-3H-indol-2-one (437 mg, 91.96%) as a black solid. MS (ESI): mass calcd for C15H14N2O: 238.11 m / z, found 239.15[M+H]+. 1-(1-benzyl-2-oxo-3H-indol-5-yl)-3-tert-butylurea To a solution of 5-amino-1-benzyl-3H-indol-2-one (200 mg, 0.839 mmol, 1 equiv) and 2- isocyanato-2-methylpropane (124.2 mg, 1.253 mmol, 1.49 equiv) in DCM (2 mL) was added TEA (253.2 mg, 2.502 mmol, 2.98 equiv). The reaction was stirred at rt for 16h. Quenched with water (10 mL) and extracted with EA (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by preparative HPLC using a XBridge Prep OBD C18 Column 150 mm x 30 mm x 5 μm column (eluent: 17% to 42% (v / v) CH3CN and H2O with 10mmol / L NH4HCO3) to afford the title compound 1-(1-benzyl-2-oxo-3H-indol-5-yl)-3-tert-butylurea (26.3 mg, 9.27%) as a white solid. LC / MS (ESI): mass calcd. for C20H23N3O2:337.18 m / z, found:338.00 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.08 (s, 1H), 7.42 (m, 1H), 7.23-7.34 (m, 5H), 7.02 (m, 1H), 6.70 (m, 1H), 5.88 (s, 1H), 4.84 (s, 2H), 3.63 (s, 2H), 1.27 (s, 9H). Example 32: 1-(1-benzyl-3-isopropyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(tert-butyl)u rea Synthetic Scheme

[0012] 3-isopropyl-3,4-dihydroquinolin-2(1H)-one To a solution of 3,4-dihydro-1H-quinolin-2-one (2 g, 13.589 mmol, 1 equiv) in THF (70 mL) was added 2M LDA (in THF) (17 mL) at -78 °C under N2. The resulting mixture was stirred 30 min at -78 °C. The reaction mixture was added 2-bromopropane (2.01 g, 16.343 mmol, 1.2 equiv) at -78 °C. The resulting mixture was stirred 30 min at -78 °C and then stirred 16 h at rt. The reaction mixture was quenched by water (50 mL) and extracted with EA (3 x 70 mL).The combined organic extracts were washed with brine (50 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 3-isopropyl-3,4-dihydro-1H-quinolin-2-one (1 g, 21.98%) as a white solid. MS (ESI): mass calcd. for C12H15NO, 189.12 m / z, found 190.30 [M+H]+. 3-isopropyl-7-nitro-3,4-dihydroquinolin-2(1H)-one To a solution of 3-isopropyl-3,4-dihydro-1H-quinolin-2-one (510 mg, 2.695 mmol, 1 equiv) in H2O (2 mL) and H2SO4 (9 mL) was added HNO3 (0.2 mL)at -10 °C. The resulting mixture was stirred at -10 °C until the starting material was totally consumed by LCMS. The reaction mixture was quenched by water. The mixture was acidified pH = 7 with NaHCO3(aq.) and then extracted with EA (3 x 50 mL). The combined organic extracts were washed with brine (50 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 3-isopropyl- 7-nitro-3,4-dihydro-1H-quinolin-2-one (200 mg, 24.28%) as a white solid. MS (ESI): mass calcd. for C12H14N2O3, 234.10 m / z, found 235.05 [M+H]+. 1-benzyl-3-isopropyl-7-nitro-3,4-dihydroquinolin-2(1H)-one To a solution of 3-isopropyl-7-nitro-3,4-dihydro-1H-quinolin-2-one (140 mg, 0.598 mmol, 1 equiv) in DMF (5 mL) was added K2CO3(247.7 mg, 1.793 mmol, 3 equiv) and benzyl bromide (112.4 mg, 0.657 mmol, 1.1 equiv). The resulting mixture was stirred 16 h at rt. The mixture was diuted with EtOAc (100 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 1-benzyl-3-isopropyl-7-nitro-3,4-dihydroquinolin- 2(1H)-one (100 mg, 49.05%) as a yellow solid. MS (ESI): mass calcd. for C19H20N2O3324.15 m / z, found 325.05 [M+H]+. 7-amino-1-benzyl-3-isopropyl-3,4-dihydroquinolin-2(1H)-one To a solution of 1-benzyl-3-isopropyl-7-nitro-3,4-dihydroquinolin-2(1H)-one (140 mg, 0.432 mmol, 1 equiv) in MeOH (10 mL) was added Pd / C (30 mg). The reaction mixture was then stirred for 1 h under hydrogen atmosphere (balloon). The reaction mixture was filtered through a pad of Celite and concentrated under reduced pressure to afford 7-amino-1-benzyl-3- isopropyl-3,4-dihydroquinolin-2(1H)-one (100 mg, 77.79%) as a yellow solid. MS (ESI): mass calcd. for C19H22N2O, 294.17 m / z, found 295.10 [M+H]. 1-(1-benzyl-3-isopropyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(tert-butyl)urea To a solution of 7-amino-1-benzyl-3-isopropyl-3,4-dihydroquinolin-2(1H)-one (100 mg, 0.340 mmol, 1 equiv) in DCM (5 mL) was added TEA (103.1 mg, 1.019 mmol, 3 equiv) and 2- isocyanato-2-methylpropane (101.0 mg, 1.019 mmol, 3 equiv). The resulting mixture was stirred for 16 h at rt. The reaction mixture was quenched by water and extracted with EA (3 x 30 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column eluted with PE / EA (2:1) & Prep-HPLC (Column: XSelect CSH Fluoro Phenyl, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 31% B to 46% B in 10.5 min; Wave Length: 220 nm; RT1(min): 11.2; Number Of Runs: 7) to afford 1-(1-benzyl-3-isopropyl-2-oxo-3,4-dihydroquinolin-6-yl)-3-tert- butylurea (3.3 mg, 2.46%) as a white solid. MS (ESI): mass calcd. for C24H31N3O2, 393.24 m / z, found 394.20 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.11 (s, 1H), 7.13 – 7.37 (m, 6H), 6.96 (dd, J = 8.6, 2.4 Hz, 1H), 6.76 (d, J = 8.7 Hz, 1H), 5.93 (s, 1H), 5.09 (d, J = 3.5 Hz, 2H), 2.92 (dd, J = 15.7, 5.3 Hz, 1H), 2.77 (dd, J = 15.7, 8.1 Hz, 1H), 2.36 (q, J = 6.9 Hz, 1H), 1.98 (p, J = 6.4 Hz, 1H), 1.26 (s, 9H), 0.94 (dd, J = 17.0, 6.7 Hz, 6H). Example 33: 3-tert-butyl-1-{4-[(3-chlorophenyl)methyl]-3-oxo-2H-1,4-benzoxazin-7-yl}urea 4-[(3-chlorophenyl)methyl]-7-nitro-2H-1,4-benzoxazin-3-one To a solution of 7-nitro-2,4-dihydro-1,4-benzoxazin-3-one (500 mg, 2.575 mmol, 1 equiv) and 1-(bromomethyl)-3-chlorobenzene (794 mg, 3.863 mmol, 1.5 equiv) in dimethylformamide (10 mL) was added Cs2CO3 (2.538 g, 7.766 mmol, 3.02 equiv). The reaction was stirred at rt for 3h. Quenched with water (50 mL) and extracted with EA (3 x 50 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 4-[(3-chlorophenyl)methyl]-7-nitro-2H-1,4-benzoxazin-3-one (203 mg, 24.73%) as a white solid. MS (ESI): mass calcd for C15H11ClN2O4: 318.04 m / z, found 319.00[M+H]+. 7-amino-4-[(3E)-4-chloro-2-methylidenebut-3-en-1-yl]-2H-1,4-benzoxazin-3-one To a mixture of 4-[(3-chlorophenyl)methyl]-7-nitro-2H-1,4-benzoxazin-3-one (700 mg, 2.196 mmol, 1 equiv) and NH4Cl (1.17g, 21.960 mmol, 10 equiv) in ethyl alcohol / water (10 mL, 10 / 1) was added Fe (1.23 g, 21.960 mmol, 10 equiv). The reaction was stirred at 60 °C for 6h. Quenched with water (20 mL) and extracted with EA (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 7-amino-4-[(3E)- 4-chloro-2-methylidenebut-3-en-1-yl]-2H-1,4-benzoxazin-3-one (183 mg, 31.48%) as a white solid. MS (ESI): mass calcd for C15H13ClN2O2: 288.07m / z, found 289.00[M+H]+. 3-tert-butyl-1-{4-[(3-chlorophenyl)methyl]-3-oxo-2H-1,4-benzoxazin-7-yl}urea To a solution of 7-amino-4-[(3-chlorophenyl)methyl]-2H-1,4-benzoxazin-3-one (200 mg, 0.693 mmol, 1 equiv) and 2-isocyanato-2-methylpropane (103.00 mg, 1.039 mmol, 1.5 equiv) in DCM (2 mL) was added TEA (210.29 mg, 2.079 mmol, 3 equiv). The reaction was stirred at rt for 3h. Quenched with water (10 mL) and extracted with EA (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by preparative HPLC using a XBridge Prep OBD C18 Column 150 mm x 30 mm x 5 μm (eluent: 17% to 42% (v / v) CH3CN and H2O with 10mmol / L NH4HCO3) to afford the title compound 3-tert-butyl-1-{4-[(3-chlorophenyl)methyl]-3-oxo-2H-1,4-benzoxazin-7-yl}urea (45.7 mg, 16.97%). LC / MS (ESI): mass calcd. for C20H22ClN3O3:387.13 m / z, found:387.95 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.23 (s, 1H), 7.29 – 7.41 (m, 3H), 7.22 (m, 2H), 6.86-6.85 (m, 2H), 5.94 (s, 1H), 5.11 (s, 2H), 4.76 (s, 2H), 1.26 (s, 9H). Example 34 and Example 35: (R)-1-(tert-butyl)-3-(3-oxo-4-(1-phenylethyl)-3,4-dihydro-2H- benzo[b][1,4]oxazin-7-yl)urea and (S)-1-(tert-butyl)-3-(3-oxo-4-(1-phenylethyl)-3,4-dihydro -2H-benzo[b][1,4]oxazin-7-yl)urea Synthetic Scheme 7-nitro-4-(1-phenylethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one To a solution of 7-nitro-2,4-dihydro-1,4-benzoxazin-3-one (500 mg, 2.575 mmol, 1 equiv) in DMF (20 mL) was added Cs2CO3(1683.41 mg, 5.150 mmol, 2 equiv) and (1- bromoethyl)benzene (714.92 mg, 3.863 mmol, 1.5 equiv). The reaction was stirred at rt for 3 hours. Quenched with water (25 mL) and extracted with EA (3 x 25 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 7-nitro-4-(1- phenylethyl)-2H-1,4-benzoxazin-3-one (564 mg, 73.42%) as a yellow liquid. MS (ESI): mass calcd. for C16H14N2O4: 298.30m / z, found 299.00 [M+H]+. 7-amino-4-(1-phenylethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one To a solution of 6-nitro-1-(1-phenylethyl)-3,4-dihydroquinolin-2-one (560 mg, 1.890 mmol, 1 equiv) in MeOH / H2O (22 mL, 10:1) was added Fe (527.68 mg, 9.450 mmol, 5 equiv) and NH4Cl (505.43 mg, 9.450 mmol, 5 equiv). The reaction was stirred at 80oC for 1 hour. The reaction was quenched with water at rt. The resulting mixture was filtered, the filter cake was washed with EA (3 x 10 mL). The filtrate was added water (20 mL) and extracted with EA (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0- 100%) to give 6-amino-1-(1-phenylethyl)-3,4-dihydroquinolin-2-one (382 mg, 75.89%) as a yellow oil. MS (ESI): mass calcd. for C16H16N2O2: 268.32m / z, found 269.15 [M+H]+. 1-(tert-butyl)-3-(3-oxo-4-(1-phenylethyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)urea To a solution of 6-amino-1-[(3-fluorophenyl)methyl]-3,4-dihydroquinolin-2-one (380 mg, 1.406 mmol, 1 equiv) in DCM (15 mL) was added 2-isocyanato-2-methylpropane (557.45 mg, 5.624 mmol, 4 equiv) and TEA (426.77 mg, 4.218 mmol, 3 equiv) at 0oC. The reaction was stirred at rt for 1 days. Quenched with water (10 mL) and extracted with EA (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by preparative HPLC using a XBridge Prep OBD C18 Column, 30*150 mm, 5μm column (eluent: 17% to 42% (v / v) CH3CN and H2O with 10mmol / L NH4HCO3) to afford the title compound 3-tert-butyl-1-{1-[(3-fluorophenyl)methyl]-2-oxo-3,4-dihydroquinolin- 6-yl}urea (120 mg, 23.11%) .LC / MS (ESI): mass calcd. for C21H25N3O3:367.45 m / z, found:368.00 [M+H]+. (R)-1-(tert-butyl)-3-(3-oxo-4-(1-phenylethyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)urea and (S)-1-(tert-butyl)-3-(3-oxo-4-(1-phenylethyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7- yl)urea A sample of 3-tert-butyl-1-[3-oxo-4-(1-phenylethyl)-2H-1,4-benzoxazin-7-yl]urea (120 mg) was separated by chiral-HPLC using a CHIRAL ART Amylose-SA, 2*25 cm, 5 μm column (eluent: 30% to 30% (v / v) Hex(0.5% 2M NH3-MeOH) and EtOH) to yield first enantiomer 3- tert-butyl-1-{3-oxo-4-[(1R)-1-phenylethyl]-2H-1,4-benzoxazin-7-yl}urea (37.1 mg) as a white solid. MS(ESI): mass calcd. for C21H25N3O3: 367.45, found: 368.20 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 7.99 – 8.31 (m, 1H), 7.11 – 7.44 (m, 6H), 6.43 – 6.67 (m, 2H), 6.04 – 6.24 (m, 1H), 5.80 – 5.98 (m, 1H), 4.55 – 4.80 (m, 2H), 1.67 – 1.80 (m, 3H), 1.22 – 1.31 (m, 9H). And to yield second enantiomer 3-tert-butyl-1-{3-oxo-4-[(1S)-1-phenylethyl]-2H-1,4- benzoxazin-7-yl}urea (22.7 mg) as a white solid. MS(ESI): mass calcd. for C21H25N3O3: 367.45, found: 368.20 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.10 – 8.26 (m, 1H), 7.17 – 7.40 (m, 6H), 6.45 – 6.70 (m, 2H), 6.02 – 6.21 (m, 1H), 5.85 – 6.00 (m, 1H), 4.60 – 4.70 (m, 2H), 1.70 – 1.80 (m, 3H), 1.20 – 1.30 (m, 9H). Example 36 and Example 37: (R)-1-(tert-butyl)-3-(4-(1-(3-chlorophenyl)ethyl)-3-oxo-3,4-di hydro-2H-benzo[b][1,4]oxazin-7-yl)urea and (S)-1-(tert-butyl)-3-(4-(1-(3-chlorophenyl)ethy l)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)urea 1-(1-bromoethyl)-3-chlorobenzene To a solution of 1-(3-chlorophenyl)ethanol (1.5 g, 9.578 mmol, 1 equiv) in Et2O (10 mL) was added PBr3(5.19 g, 19.156 mmol, 2 equiv) at 0oC. The reaction was stirred at rt for 2 hours. Quenched with water (10 mL) and extracted with EA (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. This resulted in 1-(1- bromoethyl)-3-chlorobenzene (762 mg, 36.24%) as a white oil. MS (ESI): mass calcd. for C8H8BrCl: 219.51 m / z, found 220.95 [M+H]+. 4-(1-(3-chlorophenyl)ethyl)-7-nitro-2H-benzo[b][1,4]oxazin-3(4H)-one To a solution of 7-nitro-2,4-dihydro-1,4-benzoxazin-3-one (500 mg, 2.575 mmol, 1 equiv) in DMF (15 mL) was added Cs2CO3(1683.4 mg, 5.151 mmol, 2 equiv) and 1-(1- bromoethyl)-3-chlorobenzene (565.2 mg, 2.575 mmol, 1 equiv). The final reaction mixture was stirred for 2 hours at rt. Quenched with water (25 mL) and extracted with EA (3 x 25 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 4-[1-(3-chlorophenyl)ethyl]-7-nitro-2H-1,4-benzoxazin-3-one (560 mg, 73.40%) as a yellow solid. MS (ESI): mass calcd. for C16H13ClN2O4: 332.74 m / z, found 333.00 [M+H]+. 7-amino-4-(1-(3-chlorophenyl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one To a solution of 1-[1-(3-chlorophenyl)ethyl]-6-nitro-3,4-dihydroquinolin-2-one (560 mg, 1.693 mmol, 1 equiv) in MeOH / H2O (22 mL, 10:1) was added Fe (472.73 mg, 8.465 mmol, 5 equiv) and NH4Cl (452.80 mg, 8.465 mmol, 5 equiv). The reaction was stirred at 80oC for 1 hour. The reaction was stirred for 1 hour at 80oC. The reaction was quenched with water at rt. After filtration, the filter cake was washed with EA (3 x 20 mL). The filtrate was added water (20 mL) and extracted with EA (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 6-amino-1-[1-(3- chlorophenyl)ethyl]-3,4-dihydroquinolin-2-one (470 mg, 92.29%) as a yellow oil. MS (ESI): mass calcd. for C16H15ClN2O2: 302.76 m / z, found:303.00 [M+H]+. 1-(tert-butyl)-3-(4-(1-(3-chlorophenyl)ethyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7- yl)urea To a solution of 6-amino-1-[1-(3-chlorophenyl)ethyl]-3,4-dihydroquinolin-2-one (470 mg, 1.563 mmol, 1 equiv) in DCM (15 mL) was added 2-isocyanato-2-methylpropane (619.60 mg, 6.252 mmol, 4 equiv) and TEA (474.36 mg, 4.689 mmol, 3 equiv) at 0oC. The reaction was stirred at rt for 1 day. Quenched with water (10 mL) and extracted with EA (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by preparative HPLC using a YMC-Actus Triart C18 ExRS, 30*150 mm, 5μm column (eluent: 49% to 69% (v / v) CH3CN and H2O with 10mmol / L NH4HCO3) to afford the title compound 3-tert-butyl-1-{1-[1-(3-chlorophenyl)ethyl]-2-oxo-3,4- dihydroquinolin-6-yl}urea (470 mg, 74.8%) as a white solid. MS (ESI): mass calcd for C21H24ClN3O3:401.89 m / z, found:402.00 [M+H]+. (R)-1-(tert-butyl)-3-(4-(1-(3-chlorophenyl)ethyl)-3-oxo-3,4-dihydro-2H- benzo[b][1,4]oxazin-7-yl)urea and (S)-1-(tert-butyl)-3-(4-(1-(3-chlorophenyl)ethyl)-3-oxo- 3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)urea A sample of 3-tert-butyl-1-{4-[1-(3-chlorophenyl)ethyl]-3-oxo-2H-1,4-benzoxazin-7- yl}urea (200 mg) was separated by chiral-HPLC using a CHIRALPAK IG, 2*25 cm, 5 μm column (eluent: 30% to 30% (v / v) Hex(0.5% 2M NH3-MeOH) and EtOH) to yield first enantiomer example 3-tert-butyl-1-{4-[(1R)-1-(3-chlorophenyl)ethyl]-3-oxo-2H-1,4-benzoxazin- 7-yl}urea (48.0 mg) as a white solid. LC / MS: mass calcd. for C21H24ClN3O3: 401.89, found:402.15 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.10 – 8.30 (m, 1H), 7.30 – 7.44 (m, 3H), 7.20 – 7.30 (m, 2H), 6.51 – 6.72 (m, 2H), 5.99 – 6.16 (m, 1H), 5.81 – 5.99 (m, 1H), 4.59 – 4.78 (m, 2H), 1.68 – 1.78 (m, 3H), 1.24 – 1.29 (m, 9H). And to yield second enantiomer example 3-tert-butyl-1-{4-[(1S)-1-(3-chlorophenyl)ethyl]-3-oxo-2H-1,4-benzoxazin-7-yl}urea (26.2 mg) as a white solid. MS(ESI): mass calcd. for C21H24ClN3O3: 401.89, found:402.15 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 7.96 – 8.35 (m, 1H), 7.30 – 7.49 (m, 4H), 6.65 – 6.75 (m, 1H), 6.48 – 6.51 (m, 1H), 6.00 – 6.17 (m, 1H), 5.81 – 6.00 (m, 1H), 4.60 – 4.80 (m, 2H), 1.68 – 1.81 (m, 3H), 1.18 – 1.44 (m, 9H). Example 38: 1-(3-benzyl-2-oxo-2,3-dihydrobenzo[d]oxazol-6-yl)-3-(tert-butyl)urea 3-benzyl-6-nitrobenzo[d]oxazol-2(3H)-one To a solution of 6-nitrobenzo[d]oxazol-2(3H)-one (300 mg, 1.666 mmol, 1 equiv) in CH3CN (6 mL) was added KI (276.49 mg, 1.666 mmol, 1 equiv), K2CO3 (788.35 mg, 5.664 mmol, 3.4 equiv) and benzyl bromide (112.4 mg, 0.657 mmol, 1.1 equiv). The resulting mixture was stirred for 5 h at 60 °C. The mixture was diuted with EtOAc (100 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 3-benzyl-6- nitrobenzo[d]oxazol-2(3H)-one (300 mg, 66.65%) as a yellow solid. MS (ESI): mass calcd. for C14H10N2O4270.06 m / z, found 271.05 [M+H]+. 6-amino-3-benzylbenzo[d]oxazol-2(3H)-one To a solution of 3-benzyl-6-nitrobenzo[d]oxazol-2(3H)-one (200 mg, 0.740 mmol, 1 equiv) in MeOH (10 mL) was added Pd / C (50 mg). The reaction mixture was then stirred for 1 h under hydrogen atmosphere (balloon). The reaction mixture was filtered through a pad of Celite and concentrated under reduced pressure to afford 6-amino-3-benzylbenzo[d]oxazol-2(3H)-one (150 mg, 84.36%) as a white solid. MS (ESI): mass calcd. for C14H12N2O2, 240.09 m / z, found 241.20 [M+H]+. 1-(3-benzyl-2-oxo-2,3-dihydrobenzo[d]oxazol-6-yl)-3-(tert-butyl)urea To a solution of 6-amino-3-benzylbenzo[d]oxazol-2(3H)-one (100 mg, 0.416 mmol, 1 equiv) in DCM (8 mL) was added TEA (126.3 mg, 1.249 mmol, 3 equiv) and 2-isocyanato-2- methylpropane (123.7 mg, 1.249 mmol, 3 equiv). The resulting mixture was stirred for 16 h at rt. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column eluted with PE / EA (2:1) & Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 17% B to 42% B in 9 min, 42% B; Wave Length: 254 / 220 nm; RT1(min): 8.9; Number Of Runs: 0) to afford 1-(3-benzyl-2-oxo-2,3-dihydrobenzo[d]oxazol-6- yl)-3-(tert-butyl)urea (12.8 mg, 9.03%) as a off-white solid. MS (ESI): mass calcd. for C19H21N3O3, 339.16 m / z, found 340.10 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.30 (s, 1H), 7.61 (d, J = 1.9 Hz, 1H), 7.27 – 7.39 (m, 5H), 7.01 (d, J = 8.5 Hz, 1H), 6.89 (dd, J = 8.5, 2.0 Hz, 1H), 5.95 (s, 1H), 4.99 (s, 2H), 1.27 (s, 9H). Example 39: 1-(tert-butyl)-3-(1-(2-fluoro-5-(trifluoromethyl)benzyl)-2-oxo-1,2,3,4-tetrahyd roquinolin-6-yl)urea 1-(2-fluoro-5-(trifluoromethyl)benzyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one To a solution of 6-nitro-3,4-dihydroquinolin-2(1H)-one (500 mg, 2.602 mmol, 1 equiv) in DMF (10 mL) was added Cs2CO3(1.695 g, 5.20 mmol, 2 equiv) and 2-(bromomethyl)-1-fluoro- 4-(trifluoromethyl)benzene (735.1 mg, 2.860 mmol, 1.1 equiv). The resulting mixture was stirred for 16 h at rt. The mixture was diuted with EtOAc (100 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 7-nitro-4-(3- (trifluoromethyl)benzyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (533.4 mg, 55.66%) as a white solid. MS (ESI): mass calcd. for C17H12F4N2O3: 368.08 m / z, found 369.10 [M+H]+. 6-amino-1-(2-fluoro-5-(trifluoromethyl)benzyl)-3,4-dihydroquinolin-2(1H)-one To a solution of 7-nitro-4-(3-(trifluoromethyl)benzyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (200 mg, 0.543 mmol, 1 equiv) in MeOH (10 mL) was added Pd / C (50 mg). The reaction mixture was then stirred for 1 h under hydrogen atmosphere (balloon). The reaction mixture was filtered through a pad of Celite and concentrated under reduced pressure to afford 6-amino-1-(2- fluoro-5-(trifluoromethyl)benzyl)-3,4-dihydroquinolin-2(1H)-one (130 mg, 71.0%) as a white solid. MS (ESI): mass calcd. for C17H14F4N2O, 338.10 m / z, found 339.05 [M+H]+. 1-(tert-butyl)-3-(1-(2-fluoro-5-(trifluoromethyl)benzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6- yl)urea To a stirred solution of 6-amino-1-(2-fluoro-5-(trifluoromethyl)benzyl)-3,4- dihydroquinolin-2(1H)-one (130 mg, 0.384 mmol, 1 equiv) in DCM (6 mL) & toluene (2 mL) was added 2-isocyanato-2-methylpropane (114.34 mg, 1.153 mmol, 3 equiv) stirred 16 h at 90 °C. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column eluted with PE / EA (2:1) & Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 17% B to 45% B in 9 min, 45% B; Wave Length: 254 / 220 nm; RT1(min): 8.9; Number Of Runs: 0) to afford 1-(tert-butyl)-3-(1-(2-fluoro-5- (trifluoromethyl)benzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea (22.5 mg, 13.39%) as a white solid. MS (ESI): mass calcd. for C22H23F4N3O2, 437.17 m / z, found 438.15 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.15 (s, 1H), 7.66 – 7.78 (m, 1H), 7.48 (d, J = 9.3 Hz, 1H), 7.29 – 7.41 (m, 2H), 7.03 (dd, J = 8.7, 2.5 Hz, 1H), 6.81 (d, J= 8.8 Hz, 1H), 5.94 (s, 1H), 5.18 (s, 2H), 2.81 – 2.96 (m, 2H), 2.60 – 2.71 (m, 2H), 1.26 (s, 9H). Example 40: 1-(tert-butyl)-3-(4-(3-methylbenzyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazi n-7-yl)urea 4-(3-methylbenzyl)-7-nitro-2H-benzo[b][1,4]oxazin-3(4H)-one To a stirred solution of 7-nitro-2,4-dihydro-1,4-benzoxazin-3-one (500 mg, 2.575 mmol, 1 equiv) in anhydrous dimethylformamide (10 mL) was added 1-(bromomethyl)-3- methylbenzene (619.59 mg, 3.348 mmol, 1.3 equiv) and Cs2CO3(2.52 g, 7.725 mmol, 3 equiv) at rt and stirred for overnight. The reaction progress was monitored by LCMS. After completion of reaction, the resulting mixture was extracted with EA (3 x 30 mL). The combined organic layers were washed with brine (1 x 30 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (PE / EA=3:1) to afford 4-[(3-methylphenyl)methyl]-7-nitro-2H-1,4- benzoxazin-3-one (750 mg, 97.63%) as a yellow solid. MS (ESI): mass calcd. for C16H14N2O4: 298.10 m / z, found 299.05 [M +H]+. 7-amino-4-(3-methylbenzyl)-2H-benzo[b][1,4]oxazin-3(4H)-one To a solution of 4-[(3-methylphenyl)methyl]-7-nitro-2H-1,4-benzoxazin-3-one (300 mg, 1.006 mmol, 1 equiv) in 20 mL MeOH was added Pd / C (10%, 150mg) under nitrogen atmosphere in a 50 mL bar. The mixture was hydrogenated at room temperature for 30 min under hydrogen atmosphere using a hydrogen balloon, filtered through a Celite pad and concentrated under reduced pressure. This resulted in 7-amino-4-[(3-methylphenyl)methyl]-2H- 1,4-benzoxazin-3-one (250 mg, 92.65%) as a white solid. MS (ESI): mass calcd. for C16H16N2O2: 268.12 m / z, found 269.10 [M +H]+. 1-(tert-butyl)-3-(4-(3-methylb enzyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)urea To a stirred solution of 7-amino-4-[(3-methylphenyl)methyl]-2H-1,4-benzoxazin-3-one (50 mg, 0.186 mmol, 1 equiv) in DCM (5 mL) and Toluene (2.5 mL) was added 2-isocyanato-2- methylpropane (55.42 mg, 0.558 mmol, 3 equiv) at 90 °C and stirred for overnight. The reaction progress was monitored by TLC. After completion of reaction, the reaction mixture was concentrated under reduced pressure to give crude product which was further purified by HPLC with the following conditions Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 17% B to 42% B in 9 min, 42% B; Wave Length: 254 / 220 nm; RT1(min): 8.9; Number Of Runs: 0 to afford 3-tert-butyl-1-{4-[(3-methylphenyl)methyl]-3-oxo-2H-1,4- benzoxazin-7-yl}urea (2.6 mg, 3.74%) as a white solid. MS (ESI):mass calcd. for C21H25N3O3: 367.19 m / z, found 368.20 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.20 (s, 1H), 7.19 (d, J = 6.2 Hz, 2H), 7.06 (d, J = 7.3 Hz, 3H), 6.85 (d, J = 8.6 Hz, 1H), 6.75 (d, J = 8.8 Hz, 1H), 5.93 (s, 1H), 5.06 (s, 2H), 4.74 (s, 2H), 2.27 (s, 3H), 1.26 (s, 9H). Example 41 and Example 42: (R)-1-(4-benzyl-2-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4] oxazin-7-yl)-3-(tert-butyl)urea and (S)-1-(4-benzyl-2-methyl-3-oxo-3,4-dihydro-2H-benzo[b ][1,4]oxazin-7-yl)-3-(tert-butyl)urea Synthetic Scheme 4-benzyl-2-methyl-7-nitro-2H-benzo[b][1,4]oxazin-3(4H)-one To a solution of 2-methyl-7-nitro-2,4-dihydro-1,4-benzoxazin-3-one (300 mg, 1.441 mmol, 1 equiv) in DMF (10 mL) was added Cs2CO3 (941.99 mg, 2.882 mmol, 2 equiv) and benzyl bromide (369.72 mg, 2.162 mmol, 1.5 equiv). The reaction was stirred at rt for 1 hour. Quenched with water (10 mL) and extracted with EA (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 4-benzyl-2- methyl-7-nitro-2H-1,4-benzoxazin-3-one (377 mg, 87.70%) as a yellow solid. MS (ESI): mass calcd. for C16H14N2O4: 298.30m / z, found 299.00 [M+H]+. 7-amino-4-benzyl-2-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one To a solution of 6-nitro-1-(1-phenylethyl)-3,4-dihydroquinolin-2-one (560 mg, 1.890 mmol, 1 equiv) in MeOH / H2O (22 mL, 10:1) was added Fe (527.68 mg, 9.450 mmol, 5 equiv) and NH4Cl (505.43 mg, 9.450 mmol, 5 equiv). The reaction was stirred at 80oC for 1 hour. The reaction was quenched with water at rt. After filtration, the filter cake was washed with EA (3 x 10 mL). The filtrate was added water (20 mL) and extracted with EA (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 7- amino-4-benzyl-2-methyl-2H-1,4-benzoxazin-3-one (530 mg, 99.87%) as a yellow oil. MS (ESI): mass calcd. for C16H16N2O2: 268.32m / z, found 269.05 [M+H]+. 1-(4-benzyl-2-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-3-(tert-butyl)urea To a solution of 7-amino-4-benzyl-2-methyl-2H-1,4-benzoxazin-3-one (540 mg, 2.013 mmol, 1 equiv) in DCM / Toluene (15 mL, 2:1) was added 2-isocyanato-2-methylpropane (798.04 mg, 8.052 mmol, 4 equiv). The reaction was stirred at 90oC for 2 hours. Quenched with water (20 mL) and extracted with EA (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 1-(4-benzyl-2-methyl-3-oxo-2H-1,4- benzoxazin-7-yl)-3-tert-butylurea (498 mg, 67.34%) as a white solid. MS (ESI): mass calcd. for C21H25N3O3:367.45 m / z, found:368.10 [M+H]+. (R)-1-(4-benzyl-2-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-3-(tert- butyl)urea and (S)-1-(4-benzyl-2-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-3- (tert-butyl)urea A sample of 1-(4-benzyl-2-methyl-3-oxo-2H-1,4-benzoxazin-7-yl)-3-tert-butylurea (200 mg) was separted by chiral-HPLC using a CHIRALPAK IE, 2*25 cm, 5 μm column (eluent: 15% to 15% (v / v) Hex(0.5% 2M NH3-MeOH) and EtOH) to yield first enantiomer example 1- [(2R)-4-benzyl-2-methyl-3-oxo-2H-1,4-benzoxazin-7-yl]-3-tert-butylurea (29.8 mg) as a white solid. MS(ESI): mass calcd. for C21H25N3O3: 367.45, found: 368.15 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.14 – 8.32 (m, 1H), 7.15 – 7.45 (m, 6H), 6.68 – 6.98 (m, 2H), 5.79 – 6.09 (m, 1H), 5.00 – 5.17 (m, 2H), 4.70 – 4.90 (m, 1H), 1.43 – 1.65 (m, 3H), 1.18 – 1.31 (m, 9H). And to yield second enantiomer example 1-[(2S)-4-benzyl-2-methyl-3-oxo-2H-1,4-benzoxazin- 7-yl]-3-tert-butylurea (25.5 mg) as a white solid. MS(ESI): mass calcd. for C21H25N3O3: 367.45, found: 368.15 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.08 – 8.31 (m, 1H), 7.30 – 7.39 (m, 2H), 7.18 – 7.30 (m, 4H), 6.71 – 6.92 (m, 2H), 5.75 – 6.07 (m, 1H), 5.01 – 5.19 (m, 2H), 4.72 – 4.87 (m, 1H), 1.42 – 1.53 (m, 3H), 1.21 – 1.33 (m, 9H). Example 43 and Example 44: (R)-1-(tert-butyl)-3-(4-(3-chlorobenzyl)-2-methyl-3-oxo-3,4-di hydro-2H-benzo[b][1,4]oxazin-7-yl)urea and (S)-1-(tert-butyl)-3-(4-(3-chlorobenzyl)-2-met hyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)urea 4-(3-chlorobenzyl)-2-methyl-7-nitro-2H-benzo[b][1,4]oxazin-3(4H)-one To a solution of 2-methyl-7-nitro-2,4-dihydro-1,4-benzoxazin-3-one (500 mg, 2.402 mmol, 1 equiv) in DMF (10 mL) was added Cs2CO3(1569.98 mg, 4.804 mmol, 2 equiv) and 1- (bromomethyl)-3-chlorobenzene (740.30 mg, 3.603 mmol, 1.5 equiv). The reaction was stirred at rt for 1 hour. Quenched with water (10 mL) and extracted with EA (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 4- [(3-chlorophenyl)methyl]-2-methyl-7-nitro-2H-1,4-benzoxazin-3-one (790 mg, 98.85%) as a yellow solid. MS (ESI): mass calcd. for C16H13ClN2O4: 332.74 m / z, found 332.95 [M+H]+. 7-amino-4-(3-chlorobenzyl)-2-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one To a solution of 4-[(3-chlorophenyl)methyl]-2-methyl-7-nitro-2H-1,4-benzoxazin-3-one (570 mg, 1.713 mmol, 1 equiv) in EtOH (20 mL) was added SnCl2 (1641.36 mg, 8.565 mmol, 5 equiv). The reaction was stirred at 60oC for 1 hour. Quenched with water (10 mL) and extracted with EA (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 7-amino-4-[(3-chlorophenyl)methyl]-2-methyl-2H-1,4- benzoxazin-3-one (500 mg, 96.41%) as a yellow solid. MS (ESI): mass calcd. for C16H15ClN2O2: 302.76m / z, found 302.95 [M+H]+. 1-(tert-butyl)-3-(4-(3-chlorobenzyl)-2-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7- yl)urea To a solution of 7-amino-4-[(3-chlorophenyl)methyl]-2-methyl-2H-1,4-benzoxazin-3-one (500 mg, 1.651 mmol, 1 equiv) in DCM / Toluene (25 mL, 2:1) was added 2-isocyanato-2- methylpropane (654.86 mg, 6.604 mmol, 4 equiv). The reaction was stirred at 90oC for 2 hours. Quenched with water (20 mL) and extracted with EA (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 3-tert-butyl-1-{4- [(3-chlorophenyl)methyl]-2-methyl-3-oxo-2H-1,4-benzoxazin-7-yl}urea (170 mg, 25.61%) as a white solid. LC / MS (ESI): mass calcd. For C21H24ClN3O3: 401.89 m / z, found:402.05 [M+H]+. (R)-1-(tert-butyl)-3-(4-(3-chlorobenzyl)-2-methyl-3-oxo-3,4-dihydro-2H- benzo[b][1,4]oxazin-7-yl)urea and (S)-1-(tert-butyl)-3-(4-(3-chlorobenzyl)-2-methyl-3-oxo- 3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)urea A sample of 3-tert-butyl-1-{2-methyl-4-[(3-methylphenyl)methyl]-3-oxo-2H-1,4- benzoxazin-7-yl}urea (170 mg) was separated by chiral-HPLC using a CHIRALPAK IE, 2*25 cm, 5 μm column (eluent: 20% to 20% (v / v) Hex(0.5% 2M NH3-MeOH) and EtOH) to yield first enantiomer example 3-tert-butyl-1-[(2R)-2-methyl-4-[(3-methylphenyl)methyl]-3-oxo-2H-1,4- benzoxazin-7-yl]urea (23 mg) as a white solid. MS(ESI): mass calcd. for C21H24ClN3O3: 401.89, found: 402.15 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 7.93 – 8.31 (m, 1H), 7.29 – 7.44 (m, 3H), 7.13 – 7.29 (m, 2H), 6.68 – 6.99 (m, 2H), 5.84 – 6.08 (m, 1H), 4.97 – 5.21 (m, 2H), 4.71 – 4.89 (m, 1H), 1.40 – 1.58 (m, 3H), 1.21 – 1.30 (m, 9H). And to yield second enantiomer example 3-tert-butyl-1-[(2S)-2-methyl-4-[(3-methylphenyl)methyl]-3-oxo-2H-1,4-benzoxazin-7-yl]urea (24.5 mg) as a white solid. MS(ESI): mass calcd. for C21H24ClN3O3: 401.89, found: 402.15 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.00 – 8.32 (m, 1H), 7.30 – 7.49 (m, 3H), 7.19 – 7.30 (m, 2H), 6.70 – 6.92 (m, 2H), 5.81 – 6.06 (m, 1H), 5.00 – 5.21 (m, 2H), 4.66 – 4.91 (m, 1H), 1.43 – 1.54 (m, 3H), 1.25 – 1.30 (m, 9H). Example 45 and Example 45: 3-tert-butyl-1-{3-methyl-2-oxo-1-[(1S)-1-phenylethyl]-4H- quinazolin-6-yl}urea and 3-tert-butyl-1-{3-methyl-2-oxo-1-[(1R)-1-phenylethyl]-4H- quinazolin-6-yl}urea 3-methyl-6-nitro-1-(1-phenylethyl)-4H-quinazolin-2-one To a solution of 3-methyl-6-nitro-1,4-dihydroquinazolin-2-one (600 mg, 2.896 mmol, 1 equiv) and (1-bromoethyl)benzene (800 mg, 4.323 mmol, 1.49 equiv) in dimethylformamide (30 mL) was added Cs2CO3 (2802.47 mg, 8.575 mmol, 2.96 equiv). The reaction was stirred at rt for 3h. Quenched with water (50 mL) and extracted with EA (3 x 50 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 3-methyl-6-nitro- 1-(1-phenylethyl)-4H-quinazolin-2-one (765 mg, 84.85%) as a white solid. MS (ESI): mass calcd for C17H19N3O2: 311.13 m / z, found 312.20[M+H]+. 6-amino-3-methyl-1-(1-phenylethyl)-4H-quinazolin-2-one To a solution of 3-methyl-6-nitro-1-(1-phenylethyl)-4H-quinazolin-2-one (755 mg, 2.425 mmol, 1 equiv) in ethyl alcohol / water (10 mL, 10 / 1) was added iron (1354.24 mg, 24.250 mmol, 10 equiv) and NH4Cl (1297.13 mg, 24.250 mmol, 10 equiv). The reaction was stirred at 80 °C for 3h. Quenched with water (30 mL) and extracted with EA (3 x 30 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to 6-amino-3-methyl-1- (1-phenylethyl)-4H-quinazolin-2-one (200 mg, 29.31%) as a white solid. MS (ESI): mass calcd forC17H19N3O: 281.15m / z, found 282.20 [M+H]+. 1-(tert-butyl)-3-(3-methyl-2-oxo-1-(1-phenylethyl)-1,2,3,4-tetrahydroquinazolin-6-yl)urea To a solution of 6-amino-3-methyl-1-(1-phenylethyl)-4H-quinazolin-2-one (190 mg, 0.675 mmol, 1 equiv) in DCM / toluene (5 mL2 / 1) was added2-isocyanato-2-methylpropane (220.64 mg, 2.226 mmol, 3.30 equiv) The reaction was stirred at 90°C for 3h. Quenched with water (10 mL) and extracted with DCM (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 3-tert-butyl-1-{3-methyl-2-oxo-1- [(1R)-1-phenylethyl]-4H-quinazolin-6-yl}urea (178 mg, 69.3%) as a white solidLC / MS (ESI): mass calcd. for C22H28N4O2:380.22 m / z, found:381.10 [M+H]+. (S)-1-(tert-butyl)-3-(3-methyl-2-oxo-1-(1-phenylethyl)-1,2,3,4-tetrahydroquinazolin-6- yl)urea and (R)-1-(tert-butyl)-3-(3-methyl-2-oxo-1-(1-phenylethyl)-1,2,3,4- tetrahydroquinazolin-6-yl)urea. A sample of 1-(tert-butyl)-3-(3-methyl-2-oxo-1-(1-phenylethyl)-1,2,3,4- tetrahydroquinazolin-6-yl)urea (170 mg) was separated by chiral-HPLC using a (R, R)-WHELK- O1-Kromasil 2.11*25 cm, 5 μm column (eluent: MtBE(0.5% 2M NH3-MeOH)--HPLC and Hex(EtOH--HPLC) to yield first example cyclopentyl 3-tert-butyl-1-{3-methyl-2-oxo-1-[(1R)-1- phenylethyl]-4H-quinazolin-6-yl}urea (26.6 mg). LC / MS (ESI): mass calcd. for C22H28N4O2:380.22 m / z, found:381.05 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.05 (s, 1H), 7.26 – 7.37 (m, 5H), 6.80 (m, 1H), 6.37 (m, 1H), 5.92 (m, 2H), 4.32 (m, 2H), 2.92 (s, 3H), 1.74 (m, 3H), 1.19-1.25 (s, 10H). And to yield second enantiomer example cyclopentyl 3-tert-butyl-1- {3-methyl-2-oxo-1-[(1S)-1-phenylethyl]-4H-quinazolin-6-yl}urea (41.6 mg). LC / MS (ESI): mass calcd. for C22H28N4O2:380.22 m / z, found:381.10 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.05 (s, 1H), 7.26 – 7.37 (m, 5H), 6.80 (m, 1H), 6.37 (m, 1H), 5.92 (m, 2H), 4.32 (m, 2H), 2.92 (s, 3H), 1.74 (m, 3H), 1.19-1.25 (m, 10H). Example 46 and Example 52: (S)-1-(tert-butyl)-3-(1-(1-(4-chlorophenyl)ethyl)-3-methyl-2- oxo-1,2,3,4-tetrahydroquinazolin-6-yl)urea and (R)-1-(tert-butyl)-3-(1-(1-(4- chlorophenyl)ethyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-6-yl)urea 1-(1-(3-chlorophenyl)ethyl)-3-methyl-6-nitro-3,4-dihydroquinazolin-2(1H)-one To a stirred mixture of 3-methyl-6-nitro-1,4-dihydroquinazolin-2-one (500 mg, 2.413 mmol, 1 equiv) and Cs2CO3 (1.57 g, 4.826 mmol, 2 equiv) in DMF (10 mL) was added 1-(1- bromoethyl)-3-chlorobenzene (635.68 mg, 2.896 mmol, 1.2 equiv) in portions at 25°C under air atmosphere. The resulting mixture was stirred for 2h at room temperature. Desired product could be detected by LCMS. The mixture was diluted with water (50 mL). The resulting mixture was extracted with EA (3 x 50 mL). The combined organic layers were dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 1-(1-(3- chlorophenyl)ethyl)-3-methyl-6-nitro-3,4-dihydroquinazolin-2(1H)-one (640 mg, 76.70%) as a yellow solid. MS (ESI): mass calcd. for C17H16ClN3O3: 345.09 m / z, found 345.78 [M+H]+. 6-amino-1-(1-(3-chlorophenyl)ethyl)-3-methyl-3,4-dihydroquinazolin-2(1H)-one To a stirred mixture of 1-(1-(3-chlorophenyl)ethyl)-3-methyl-6-nitro-3,4- dihydroquinazolin-2(1H)-one (630 mg, 1.822 mmol, 1 equiv) and Fe (1017.48 mg, 18.220 mmol, 10 equiv) in EtOH (8 mL) and H2O (0.8 mL) was added NH4Cl (974.57 mg, 18.220 mmol, 10 equiv) in portions at 70 degrees C under air atmosphere. The resulting mixture was stirred for 2h at room temperature. Desired product could be detected by LCMS. The mixture was diluted with water (100 mL). The resulting mixture was extracted with EA (3 x 100 mL). The combined organic layers were dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 6-amino-1-(1-(3-chlorophenyl)ethyl)-3-methyl-3,4- dihydroquinazolin-2(1H)-one (240 mg, 41.71%) as a yellow solid. MS (ESI): mass calcd. for C16H16ClN3O: 315.11 m / z, found 315.80 [M +H]+. 1-(tert-butyl)-3-(1-(1-(3-chlorophenyl)ethyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-6 -yl)urea To a stirred mixture of 6-amino-1-(1-(3-chlorophenyl)ethyl)-3-methyl-3,4- dihydroquinazolin-2(1H)-one(242 mg, 0.766 mmol, 1 equiv) and 2-isocyanato-2-methylpropane (151.93 mg, 1.532 mmol, 2 equiv) in DCM (5 mL) was added TEA (232.63 mg, 2.298 mmol, 3 equiv) at 25 degrees C under air atmosphere. The resulting mixture was stirred for 2h at room temperature. Desired product could be detected by LCMS. The mixture was diluted with water (30 mL). The resulting mixture was extracted with EA (3 x 30 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 1-(tert-butyl)- 3-(1-(1-(3-chlorophenyl)ethyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-6-yl)urea (110 mg, 34.60%) as a white solid. MS (ESI): mass calcd. for C22H27ClN4O2: 414.18 m / z, found 414.93[M +H]+ (S)-1-(tert-butyl)-3-(1-(1-(4-chlorophenyl)ethyl)-3-methyl-2-oxo-1,2,3,4- tetrahydroquinazolin-6-yl)urea and (R)-1-(tert-butyl)-3-(1-(1-(4-chlorophenyl)ethyl)-3- methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-6-yl)urea The 1-(tert-butyl)-3-(1-(1-(4-chlorophenyl)ethyl)-3-methyl-2-oxo-1,2,3,4- tetrahydroquinazolin-6-yl)urea (110 mg) was separated by chiral-HPLC using a CHIRALPAK ID, 2*25 cm, 5 μm column (eluent: 10% to 10% (v / v) : EtOH--HPLC and Hex(0.5% 2M NH3- MeOH) to yield first enantiomer example (R)-1-(tert-butyl)-3-(1-(1-(4-chlorophenyl)ethyl)-3- methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-6-yl)urea (24.4 mg, 7.57%) as a white solid. LC / MS: mass calcd for C22H27ClN4O2: 414.18, found: 415.00 [M+H]+.1H-NMR (300 MHz, DMSO-d6) δ 8.07 (s, 1H), 7.32 – 7.39 (m, 1H), 7.20 – 7.30 (m, 4H), 6.80 – 6.92 (m, 1H), 6.39 (d, J = 8.8 Hz, 1H), 5.75 – 5.96 (m, 2H), 4.32 (s, 2H), 2.92 (s, 3H), 1.74 (d, J = 7.1 Hz, 3H), 1.26 (s, 9H). And to yield second enantiomer example (S)-1-(tert-butyl)-3-(1-(1-(4-chlorophenyl)ethyl)-3-methyl- 2-oxo-1,2,3,4-tetrahydroquinazolin-6-yl)urea (16.4 mg, 5.19%) as a white soild. LC / MS: mass calcd. for C22H27ClN4O2: 414.18, found: 415.00 [M+H]+.1H-NMR (300 MHz, DMSO-d6) δ 8.07 (s, 1H), 7.20 – 7.42 (m, 5H), 6.81 – 6.91 (m, 1H), 6.38 (d, J = 8.8 Hz, 1H), 5.78 – 5.96 (m, 2H), 4.32 (s, 2H), 2.91 (s, 3H), 1.73 (d, J = 7.1 Hz, 3H), 1.25 (s, 9H). Example 47: 1-(tert-butyl)-3-(1-(3-chlorobenzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazo lin-6-yl)urea 3-methyl-6-nitro-3,4-dihydroquinazolin-2(1H)-one To a stirred mixture of 3-methyl-1,4-dihydroquinazolin-2-one (1 g, 6.166 mmol, 1 equiv) in H2SO4(30 mL) was added KNO3(0.50 g, 4.933 mmol, 0.8 equiv) in portions at 0°C under air atmosphere. The resulting mixture was stirred for 2h at room temperature. Desired product could be detected by LCMS. The mixture was diluted with water (100 mL). The resulting mixture was extracted with EA (3 x 100 mL). The combined organic layers were dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 3-methyl-6- nitro-3,4-dihydroquinazolin-2(1H)-one (400 mg, 31.31%) as a white solid. MS (ESI): mass calcd. for C9H9N3O3: 207.06 m / z, found 208.19 [M+H]+. 1-(3-chlorobenzyl)-3-methyl-6-nitro-3,4-dihydroquinazolin-2(1H)-one To a stirred mixture of 3-methyl-6-nitro-3,4-dihydroquinazolin-2(1H)-one (300 mg, 1.448 mmol, 1 equiv) and 1-(bromomethyl)-3-chlorobenzene (357.03 mg, 1.738 mmol, 1.2 equiv) in DMF (5 mL) was added Cs2CO3 (1419.69 mg, 4.344 mmol, 3 equiv) in portions at 25 degrees C under air atmosphere. The resulting mixture was stirred for 2h at room temperature. Desired product could be detected by LCMS. The mixture was diluted with water (50 mL). The resulting mixture was extracted with EA (3 x 50 mL). The combined organic layers were dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 1-(3-chlorobenzyl)-3-methyl-6-nitro-3,4-dihydroquinazolin-2(1H)-one (400 mg, 83.27%) as a yellow solid. MS (ESI): mass calcd. for C16H14ClN3O3: 331.07 m / z, found 331.76 [M +H]+. 6-amino-1-(3-chlorobenzyl)-3-methyl-3,4-dihydroquinazolin-2(1H)-one To a stirred mixture of 1-(3-chlorobenzyl)-3-methyl-6-nitro-3,4-dihydroquinazolin- 2(1H)-one (395 mg, 1.191 mmol, 1 equiv) and Fe (664.90 mg, 11.910 mmol, 10 equiv) in EtOH (5 mL) and H2O (0.5 mL) was added NH4Cl (636.86 mg, 11.910 mmol, 10 equiv) in portions at 25 degrees C under air atmosphere. The resulting mixture was stirred for 2h at 60 degrees C. Desired product could be detected by LCMS. The mixture was diluted with water (50 mL). The resulting mixture was extracted with EA (3 x 50 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 6-amino-1-(3-chlorobenzyl)-3- methyl-3,4-dihydroquinazolin-2(1H)-one (160 mg, 44.53%) as a yellow solid. MS (ESI): mass calcd. for C16H16ClN3O: 301.10 m / z, found 301.77[M +H]+. 1-(tert-butyl)-3-(1-(3-chlorobenzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-6-yl)urea To a stirred mixture of 6-amino-1-(3-chlorobenzyl)-3-methyl-3,4-dihydroquinazolin-2(1H)- one (150 mg, 0.497 mmol, 1 equiv) and 2-isocyanato-2-methylpropane (98.55 mg, 0.994 mmol, 2 equiv) in dichloromethane (1 mL) was added TEA (150.90 mg, 1.491 mmol, 3 equiv) dropwise at 0 degrees C under air atmosphere. The resulting mixture was stirred for 2h at room temperature. Desired product could be detected by LCMS. The mixture was diluted with water (30 mL). The resulting mixture was extracted with EA (3 x 30 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford the 1-(tert- butyl)-3-(1-(3-chlorobenzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-6-yl)urea(31.9 mg, 15.65%) as a white solid. MS (ESI): mass calcd. for C21H25ClN4O2: 400.17 m / z, found 401.00[M +H]+.1H-NMR (300 MHz, DMSO-d6) δ 8.11 (s, 1H), 7.22 – 7.40 (m, 4H), 7.18 (d, J = 7.4 Hz, 1H), 6.90 – 6.99 (m, 1H), 6.56 (d, J = 8.7 Hz, 1H), 5.91 (s, 1H), 5.02 (s, 2H), 4.42 (s, 2H), 2.95 (s, 3H), 1.26 (s, 9H). Example 48: 1-(tert-butyl)-3-(1-(2-fluoro-3-methylbenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin 1-(2-fluoro-3-methylbenzyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one To a stirred solution of 6-nitro-3,4-dihydro-1H-quinolin-2-one (300 mg, 1.561 mmol, 1 equiv) in DMF (5 mL) was added 1-(bromomethyl)-2-fluoro-3-methylbenzene (412.08 mg, 2.029 mmol, 1.3 equiv) and Cs2CO3(1.53 g, 4.683 mmol, 3 equiv) at rt and stirred for overnight. After completion of reaction, the resulting mixture was extracted with EA (3 x 30 mL). The combined organic layers were washed with brine (1 x 30 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (3:1) to afford 1-(2-fluoro-3- methylbenzyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one (420 mg, 85.60%) as a yellow solid. MS (ESI): mass calcd. for C17H15FN2O3: 314.11 m / z, found 315.05 [M +H]+. 6-amino-1-(2-fluoro-3-methylbenzyl)-3,4-dihydroquinolin-2(1H)-one To a solution of 1-(2-fluoro-3-methylbenzyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one (200 mg, 0.636 mmol, 1 equiv) in 20 mL MeOH was added Pd / C (30 mg) under nitrogen atmosphere. The mixture was hydrogenated at room temperature for 50 min under hydrogen atmosphere using a hydrogen balloon, filtered through a Celite pad and concentrated under reduced pressure to afford 6-amino-1-(2-fluoro-3-methylbenzyl)-3,4-dihydroquinolin-2(1H)-one (160 mg, 88.44%) as a white solid. MS (ESI): mass calcd. for C17H17FN2O: 284.13 m / z, found 285.10 [M +H]+. 1-(tert-butyl)-3-(1-(2-fluoro-3-methylbenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea To a stirred solution of 6-amino-1-[(2-fluoro-3-methylphenyl)methyl]-3,4- dihydroquinolin-2-one (80 mg, 0.281 mmol, 1 equiv) in DCM (5 mL) was added 2-isocyanato-2- methylpropane (139.46 mg, 1.405 mmol, 5 equiv) and Et3N (85.41 mg, 0.843 mmol, 3 equiv) at rt and stirred for overnight. The reaction progress was monitored by LCMS. After completion of reaction, the reaction mixture was concentrated under reduced pressure to give crude product which was further purified by Prep-HPLC with the following conditions Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 17% B to 42% B in 9 min, 42% B; Wave Length: 254 / 220 nm; RT1(min): 8.9; Number Of Runs: 0 to afford 3-tert-butyl-1-{1-[(2-fluoro- 3-methylphenyl)methyl]-2-oxo-3,4-dihydroquinolin-6-yl}urea (29.0 mg, 26.78%) as a white solid. MS (ESI): mass calcd. for C22H26FN3O2: 383.20 m / z, found 384.20 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.13 (s, 1H), 7.34 (d, J = 2.4 Hz, 1H), 7.15 (t, J = 7.3 Hz, 1H), 6.92 – 7.04 (m, 2H), 6.76 – 6.88 (m, 1H), 6.71 (d, J = 8.7 Hz, 1H), 5.93 (s, 1H), 5.09 (s, 2H), 2.89 (dd, J = 8.7, 5.8 Hz, 2H), 2.65 (dd, J = 8.7, 5.8 Hz, 2H), 2.25 (d, J = 2.0 Hz, 3H), 1.27 (s, 9H). Example 49: 1-(tert-butyl)-3-(1-(2-fluoro-5-methylbenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin 1-(2-fluoro-5-methylbenzyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one To a stirred solution of 6-nitro-3,4-dihydro-1H-quinolin-2-one (300 mg, 1.561 mmol, 1 equiv) in DMF (5 mL) was added 2-(bromomethyl)-1-fluoro-4-methylbenzene (412.08 mg, 2.029 mmol, 1.3 equiv) and Cs2CO3(1.53 g, 4.683 mmol, 3 equiv) at rt and stirred for overnight. After completion of reaction, the resulting mixture was extracted with EA (3 x 20 mL). The combined organic layers were washed with brine (1 x 30 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (3:1) to afford 1-(2-fluoro-5- methylbenzyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one (400 mg, 81.52%) as a yellow solid. MS (ESI): mass calcd. for C17H15FN2O: 314.11 m / z, found 315.05 [M +H] +. 6-amino-1-(2-fluoro-5-methylbenzyl)-3,4-dihydroquinolin-2(1H)-one To a solution of 1-(2-fluoro-5-methylbenzyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one (200 mg, 0.636 mmol, 1 equiv) in 20 mL MeOH was added Pd / C (30 mg) under nitrogen atmosphere. The mixture was hydrogenated at room temperature for 30 min under hydrogen atmosphere using a hydrogen balloon, filtered through a Celite pad and concentrated under reduced pressure to afford 6-amino-1-(2-fluoro-5-methylbenzyl)-3,4-dihydroquinolin-2(1H)-one (160 mg, 88.40%) as a white solid. MS (ESI): mass calcd. for C17H17FN2O: 284.13 m / z, found 285.10 [M +H] +. 1-(tert-butyl)-3-(1-(2-fluoro-5-methylbenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea To a stirred solution of 6-amino-1-[(2-fluoro-5-methylphenyl)methyl]-3,4- dihydroquinolin-2-one (80 mg, 0.281 mmol, 1 equiv) in DCM (5 mL) was added 2-isocyanato-2- methylpropane (139.46 mg, 1.405 mmol, 5 equiv) and Et3N (85.41 mg, 0.843 mmol, 3 equiv) at rt and stirred for overnight. The reaction progress was monitored by LCMS. After completion of reaction, the reaction mixture was concentrated under reduced pressure to give crude product which was further purified by HPLC with the following conditions Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 17% B to 42% B in 9 min, 42% B; Wave Length: 254 / 220 nm; RT1(min): 8.9; Number Of Runs: 0 to afford 1-(tert-butyl)-3-(1-(2-fluoro-5- methylbenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea (8.1 mg, 7.49%) as a white solid. MS (ESI): mass calcd. for C22H26FN3O2: 383.20 m / z, found 384.20 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.13 (s, 1H), 7.34 (d, J = 2.4 Hz, 1H), 7.16 – 7.04 (m, 2H), 7.00 (dd, J = 8.7, 2.5 Hz, 1H), 6.81 (d, J = 7.5 Hz, 1H), 6.71 (d, J = 8.8 Hz, 1H), 5.93 (s, 1H), 5.06 (s, 2H), 2.89 (t, J = 7.2 Hz, 2H), 2.66 (dd, J = 8.8, 5.8 Hz, 2H), 2.19 (s, 3H), 1.27 (s, 9H). Example 50: 1-(tert-butyl)-3-(3-oxo-4-(3-(trifluoromethyl)benzyl)-3,4-dihydro-2H-benzo[b] [1,4]oxazin-7-yl)urea 7-nitro-4-(3-(trifluoromethyl)benzyl)-2H-benzo[b][1,4]oxazin-3(4H)-one To a solution of 7-nitro-2H-benzo[b][1,4]oxazin-3(4H)-one (500 mg, 2.575 mmol, 1 equiv) in DMF (10 mL) was added Cs2CO3 (1.678 g, 5.150 mmol, 2 equiv) and 1- (bromomethyl)-3-(trifluoromethyl)benzene (676.8 mg, 2.832 mmol, 1.1 equiv). The resulting mixture was stirred for 16 h at rt. The mixture was diuted with EtOAc (100 mL), washed with water (3 x 30 mL), brine (2 x 30 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 7-nitro-4- (3-(trifluoromethyl)benzyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (473.8 mg, 52.23%) as a white solid. MS (ESI): mass calcd. for C16H11F3N2O4: 352.07 m / z, found 353.05 [M+H]+. 7-amino-4-(3-(trifluoromethyl)benzyl)-2H-benzo[b][1,4]oxazin-3(4H)-one To a solution of 7-nitro-4-(3-(trifluoromethyl)benzyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (300 mg, 0.852 mmol, 1 equiv) in MeOH (10 mL) was added Pd / C (100 mg). The reaction mixture was then stirred for 1 h under hydrogen atmosphere (balloon). The reaction mixture was filtered through a pad of Celite and concentrated under reduced pressure to afford 7-amino-4-(3- (trifluoromethyl)benzyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (263.6 mg, 96.0%) as a white solid. MS (ESI): mass calcd. for C16H13F3N2O2, 322.09 m / z, found 323.05 [M+H]+. 1-(tert-butyl)-3-(3-oxo-4-(3-(trifluoromethyl)benzyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7- yl)urea To a stirred solution of 7-amino-4-(3-(trifluoromethyl)benzyl)-2H-benzo[b][1,4]oxazin- 3(4H)-one (90 mg, 0.279 mmol, 1 equiv) in DCM (6 mL) & toluene (2mL) was added 2- isocyanato-2-methylpropane (82.97 mg, 0.837 mmol, 3 equiv) stirred 16 h at 90 °C. The reaction mixture was concentrated under vacuum to yield a crude product which was directly purified Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 17% B to 42% B in 9 min, 42% B; Wave Length: 254 / 220 nm; RT1(min): 9; Number Of Runs: 0) to afford 1-(tert-butyl)-3-(3-oxo-4-(3-(trifluoromethyl)benzyl)-3,4-dihydro-2H- benzo[b][1,4]oxazin-7-yl)urea (2.1 mg, 1.7%) as a white solid. MS (ESI): mass calcd. for C21H22F3N3O3, 421.16 m / z, found 422.15 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.22 (s, 1H), 7.49 – 7.70 (m, 4H), 7.21 (d, J = 2.3 Hz, 1H), 6.87 – 6.90 (m, 1H), 6.75 – 6.79 (m, 1H), 5.94 (s, 1H), 5.19 – 5.23 (m, 2H), 4.75 – 4.78 (m, 2H), 1.23 – 1.29 (m, 9H). Example 51: 1-(1-benzyl-3-(hydroxymethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(tert- butyl)urea Synthetic Scheme 1-benzyl-6-nitro-2-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylic acid In a 50-mL round bottom flask, to a solution of 1-benzyl-6-nitro-3,4-dihydroquinolin-2- one (500 mg, 1.771 mmol, 1 equiv) in tetrahydrofuran (5 mL, 0.069 mmol, 0.04 equiv) was added dropwise 2M LDA (in THF) (1 mL, 1.948 mmol, 1.1 equiv) at -78 °C under N2. The reaction mixture was stirred at -78 °C for 30 min. The reaction was quenched with dry ice. The mixture was stirred for 10 min at rt. NH4Cl (aq.) was added into the mixture. The mixture was acidified pH = 5 with HCl (1N). The solution was extracted with EA (3 x 50 mL). The combined organic extracts were washed with brine (10 mL), dried over anhydrous Na2SO4, and concentrated under vacuum. The residue was purified by silica gel column, eluted with DCM / MeOH (8:1) to afford 1-benzyl-6-nitro-2-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylic acid (150 mg, 25.95%) as an off-white solid. MS (ESI): mass calcd. for C17H14N2O5, 326.09 m / z, found 327.05 [M+H]+. methyl 1-benzyl-6-nitro-2-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylate A solution of 1-benzyl-6-nitro-2-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylic acid (500 mg, 1.532 mmol, 1 equiv) in methanol (10 mL) was added sulfuric acid (0.1 mL) at rt. The resulting mixture was stirred for 2 h at 70 °C. Quench with water (10 mL) and extract with ethyl acetate (3 x 30 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column, eluted with PE / EA (3:1) to afford methyl 1-benzyl-6-nitro-2-oxo- 1,2,3,4-tetrahydroquinoline-3-carboxylate (150 mg, 28.76%) as white solid. MS (ESI): mass calcd. for C18H16N2O5, 340.11 m / z, found 341.05 [M+H]+. methyl 6-amino-1-benzyl-2-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylate To a solution of methyl 1-benzyl-6-nitro-2-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylate (200 mg, 0.588 mmol, 1 equiv) in MeOH (10 mL) was added Pd / C (30 mg). The reaction mixture was then stirred for 1 h under hydrogen atmosphere (balloon). The reaction mixture was filtered through a pad of Celite and concentrated under reduced pressure to afford methyl 6- amino-1-benzyl-2-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylate (150 mg, 79.36%) as a yellow solid. MS (ESI): mass calcd. for C18H18N2O3, 310.13 m / z, found 311.15 [M+H]+. methyl 1-benzyl-6-(3-(tert-butyl)ureido)-2-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylate To a stirred solution of methyl 6-amino-1-benzyl-2-oxo-1,2,3,4-tetrahydroquinoline-3- carboxylate (150 mg, 0.483 mmol, 1 equiv) in DCM (8 mL) was added 2-isocyanato-2- methylpropane (239.5 mg, 2.417 mmol, 5 equiv) and TEA (146.7 mg, 1.450 mmol, 3 equiv) stirred overnight at rt. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL).The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column eluted with PE / EA (2:1) to afford methyl 1-benzyl-6-[(tert- butylcarbamoyl)amino]-2-oxo-3,4-dihydroquinoline-3-carboxylate (70 mg, 31.95%) as a yellow solid. MS (ESI): mass calcd. for C23H27N3O4, 409.20 m / z, found 410.25 [M+H]+. 1-(1-benzyl-3-(hydroxymethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(tert-butyl)urea To a stirred solution of methyl 1-benzyl-6-[(tert-butylcarbamoyl)amino]-2-oxo-3,4- dihydroquinoline-3-carboxylate (70 mg, 0.171 mmol, 1 equiv) in MeOH (5 mL) was added NaBH4(64.6 mg, 1.709 mmol, 10 equiv) stirred 3 h at rt. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL).The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column eluted with PE / EA (2:1) & Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water (10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 17% B to 42% B in 9 min, 42% B; Wave Length: 254 / 220 nm; RT1(min): 8.9; Number Of Runs: 0) to afford 1-[1- benzyl-3-(hydroxymethyl)-2-oxo-3,4-dihydroquinolin-6-yl]-3-tert-butylurea (9.9 mg, 15.13%) as a white solid. MS (ESI): mass calcd. for C22H27N3O3, 381.21 m / z, found 382.20 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.11 (s, 1H), 7.25 – 7.36 (m, 3H), 7.12 – 7.24 (m, 3H), 6.96 (dd, J = 8.6, 2.4 Hz, 1H), 6.74 (d, J = 8.8 Hz, 1H), 5.93 (s, 1H), 5.08 (s, 2H), 4.78 (s, 1H), 3.68 – 3.83 (m, 1H), 3.59 (d, J = 10.8 Hz, 1H), 2.98 (dd, J = 15.4, 5.6 Hz, 1H), 2.75 – 2.90 (m, 1H), 2.65 – 2.75 (m, 1H), 1.26 (s, 9H). Example 53: 3-tert-butyl-1-{1-[(2-cyano-3-methylphenyl)methyl]-2-oxo-3,4-dihydroquinoli 2-methyl-6-[(6-nitro-2-oxo-3,4-dihydroquinolin-1-yl)methyl]benzonitrile To a stirred solution of 2-(bromomethyl)-6-methylbenzonitrile (400 mg, 1.904 mmol, 1 equiv) and 6-nitro-3,4-dihydro-1H-quinolin-2-one (548.88 mg, 2.856 mmol, 1.5 equiv) in DMF (15 mL) was added K2CO3(662.69 mg, 4.760 mmol, 2.5 equiv) in portions at room temperature under nitrogen atmosphere. The final reaction mixture was stirred for 2 h at room temperature. Quenched with water (20 mL) and extracted with EA (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The crude product was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 2-methyl-6-[(6- nitro-2-oxo-3,4-dihydroquinolin-1-yl)methyl]benzonitrile (400 mg, 65.38%) as a white solid. MS: mass calcd. for C18H15N3O3: 321.11 m / z, found 322.05 [M +H]+. 2-[(6-amino-2-oxo-3,4-dihydroquinolin-1-yl)methyl]-6-methylbenzonitrile To a stirred solution of 2-methyl-6-[(6-nitro-2-oxo-3,4-dihydroquinolin-1- yl)methyl]benzonitrile (400 mg, 1.245 mmol, 1 equiv) in EtOH / H2O (11 mL, 10 / 1) was added Fe (695.16 mg, 12.450 mmol, 10 equiv) and NH4Cl (665.85 mg, 12.450 mmol, 10 equiv) in portions at room temperature under nitrogen atmosphere. The final reaction mixture was stirred for 2 h at 60°C. The reaction was quenched with water at rt. After filtration, the filter cake was washed with EA (3 x 20 mL). The filtrate was added water (20 mL) and extracted with EA (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The resulting mixture was concentrated under vacuum. The crude product was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 2-[(6-amino-2- oxo-3,4-dihydroquinolin-1-yl)methyl]-6-methylbenzonitrile (300 mg, 82.72%) as a light yellow solid.MS: mass calcd. for C18H17N3O: 291.14 m / z, found 292.10 [M +H]+. 3-tert-butyl-1-{1-[(2-cyano-3-methylphenyl)methyl]-2-oxo-3,4-dihydroquinolin-6-yl}urea To a stirred solution of 2-[(6-amino-2-oxo-3,4-dihydroquinolin-1-yl)methyl]-6- methylbenzonitrile (150 mg, 0.515 mmol, 1 equiv) in toluene / DCM (10 mL, 1 / 2) was added 2- isocyanato-2-methylpropane (153.11 mg, 1.545 mmol, 3 equiv) in portions at room temperature under nitrogen atmosphere. The final reaction mixture was stirred for 3 h at 90°C. The reaction was monitored by LCMS. Quenched with water (10 mL) and extracted with EA (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The crude product was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 3-tert-butyl-1-{1-[(2-cyano-3-methylphenyl)methyl]-2-oxo-3,4- dihydroquinolin-6-yl}urea (10.3 mg, 5.10%) as a white solid. MS: mass calcd. For C23H26N4O2: 390.21 m / z, found 391.15 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.13 (s, 1H), 7.47 (t, J = 7.8 Hz, 1H), 7.35 – 7.33 (m, 2H),6.99 – 6.97 (m, 2H), 6.66 (d, J = 8.7 Hz, 1H), 5.92 (s, 1H), 5.21 (s, 2H), 2.91 (t, J = 7.8 Hz, 2H), 2.67 (m, 2H), 2.51 (s, 3H), 1.26 (s, 9H). Example 54: 1-(tert-butyl)-3-(1-(2-fluoro-3-(trifluoromethyl)benzyl)-2-oxo-1,2,3,4- tetrahydroquinolin-6-yl)urea 1-(2-fluoro-3-(trifluoromethyl)benzyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one To a solution of To a solution of 6-nitro-3,4-dihydro-1H-quinolin-2-one (500 mg, 2.602 mmol, 1 equiv) in DMF (10 mL) was added K2CO3 (431.50 mg, 3.122 mmol, 2 equiv) and 1- (bromomethyl)-2-fluoro-3-(trifluoromethyl)benzene (601.86 mg, 2.341 mmol, 1.5 equiv). The resulting mixture was stirred for 16 h at rt. The mixture was diuted with EtOAc (50 mL), washed with water (3 x 20 mL), brine (2 x 20 mL) and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford 1- (2-fluoro-3-(trifluoromethyl)benzyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one (450 mg, 78.27%) as a yellow solid. MS (ESI): mass calcd. for C17H12F4N2O3: 368.08 m / z, found 369.05 [M+H]+. 6-amino-1-(2-fluoro-3-(trifluoromethyl)benzyl)-3,4-dihydroquinolin-2(1H)-one To a solution of 1-(2-fluoro-3-(trifluoromethyl)benzyl)-6-nitro-3,4-dihydroquinolin- 2(1H)-one (430 mg, 1.168 mmol, 1 equiv) in MeOH (10 mL) was added Pd / C (100 mg). The reaction mixture was then stirred for 1 h under hydrogen atmosphere (balloon). The reaction mixture was filtered through a pad of Celite and concentrated under reduced pressure to afford 6- amino-1-(2-fluoro-3-(trifluoromethyl)benzyl)-3,4-dihydroquinolin-2(1H)-one (370 mg, 93.67%) as a yellow solid. MS (ESI): mass calcd. for C17H14F4N2O: 338.10 m / z, found 339.15 [M+H]+. 1-(tert-butyl)-3-(1-(2-fluoro-3-(trifluoromethyl)benzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6- yl)urea To a solution of 6-amino-1-(2-fluoro-3-(trifluoromethyl)benzyl)-3,4-dihydroquinolin- 2(1H)-one (150 mg, 0.443 mmol, 1 equiv) in DCM (10 mL) was added TEA (179.47 mg, 1.772 mmol, 4 equiv) and 2-isocyanato-2-methylpropane (219.77 mg, 2.215 mmol, 5 equiv). The resulting mixture was stirred for 16 h at rt. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column eluted with PE / EA (2:1) & Prep-HPLC (XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 17% B to 42% B in 9 min, 42% B; Wave Length: 254 / 220 nm; RT1(min): 8.9; Number Of Runs: 0) to afford 1-(tert-butyl)-3-(1-(2- fluoro-3-(trifluoromethyl)benzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea (45.3 mg, 23.26%) as a white solid. MS (ESI): mass calcd. for C22H23F4N3O2: 437.17, found: 437.95 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.14 (s, 1H), 7.61 – 7.72 (m, 1H), 7.25 – 7.40 (m, 3H), 6.96 – 7.05 (m, 1H), 6.77 (d, J = 8.8 Hz, 1H), 5.93 (s, 1H), 5.18 (s, 2H), 2.85 – 2.95 (m, 2H), 2.61 – 2.71 (m, 2H), 1.26 (s, 9H). Example 55: 3-tert-butyl-1-(1-{[2-cyano-5-(trifluoromethyl) phenyl] methyl}-2-oxo-3,4- dihydroquinolin-6-yl) urea Synthetic Scheme 1-bromo-2-(bromomethyl)-4-(trifluoromethyl)benzene To a stirred solution of [2-bromo-5-(trifluoromethyl) phenyl] methanol (2 g, 7.842 mmol, 1 equiv) in DCM (20 mL) was added phosphorus tribromide (2.12 g, 7.842 mmol, 1 equiv) in portions at 0°C under air atmosphere. The resulting mixture was stirred for 3 h at room temperature under air atmosphere. The reaction was quenched with water (30 mL). The resulting mixture was extracted with ethyl acetate (3 x 30 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. This resulted in 1-bromo-2- (bromomethyl)-4-(trifluoromethyl) benzene (1.3 g, 52.14%) as a yellow oil. The crude product was used in the next step directly without further purification. 1-{[2-bromo-5-(trifluoromethyl) phenyl] methyl}-6-nitro-3,4-dihydroquinolin-2-one To a stirred solution of 1-bromo-2-(bromomethyl)-4-(trifluoromethyl) benzene (1.39 g, 4.372 mmol, 1.2 equiv) and 6-nitro-3,4-dihydro-1H-quinolin-2-one (700.16 mg, 3.643 mmol, 1.0 equiv) in DMF (15 mL) was added K2CO3 (1014.40 mg, 7.287 mmol, 2 equiv) in portions at room temperature under air atmosphere. The resulting mixture was stirred for 3 h at room temperature under air atmosphere. Desired product could be detected by LCMS. The reaction was quenched with water (30 mL). The resulting mixture was extracted with ethyl acetate (3 x 30 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 1-{[2-bromo-5-(trifluoromethyl) phenyl] methyl}-6-nitro-3,4- dihydroquinolin-2-one (1.4 g, 89.76%) as a yellow oil. LC / MS: mass calcd. for C17H12BrF3N2O3: 428.00, found: 428.95 [M+H]+. 2-[(6-nitro-2-oxo-3,4-dihydroquinolin-1-yl) methyl]-4-(trifluoromethyl)benzonitrile To a stirred solution of 1-{[2-bromo-5-(trifluoromethyl) phenyl] methyl}-6-nitro-3,4- dihydroquinolin-2-one (600 mg, 1.398 mmol, 1 equiv) and Zn(CN)2 (196.98 mg, 1.678 mmol, 1.2 equiv) in DMF (10 mL) was added BrettPhos Pd G3 (253.45 mg, 0.280 mmol, 0.2 equiv) and BrettPhos (150.08 mg, 0.280 mmol, 0.2 equiv) in portions at room temperature under air atmosphere. The resulting mixture was stirred for 3 h at 120°C under nitrogen atmosphere. After cooling down to rt, the reaction was quenched with water (30 mL). The resulting mixture was extracted with ethyl acetate (3 x 30 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 2-[(6-nitro-2-oxo-3,4- dihydroquinolin-1-yl) methyl]-4-(trifluoromethyl) benzonitrile (100 mg, 19.06%) as a yellow oil. Desired product could be detected by TLC. 2-[(6-amino-2-oxo-3,4-dihydroquinolin-1-yl) methyl]-4-(trifluoromethyl)benzonitrile To a stirred solution of 2-[(6-nitro-2-oxo-3,4-dihydroquinolin-1-yl) methyl]-4- (trifluoromethyl) benzonitrile (100 mg, 0.266 mmol, 1 equiv) in AcOH was added Zn (209.04 mg, 3.192 mmol, 12 equiv) in portions at room temperature under air atmosphere. The resulting mixture was stirred for 3 h at room temperature under air atmosphere. Desired product could be detected by LCMS. The reaction was quenched with water (30 mL). The resulting mixture was extracted with ethyl acetate (3 x 30 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 2-[(6-amino-2-oxo-3,4- dihydroquinolin-1-yl) methyl]-4-(trifluoromethyl) benzonitrile (85 mg, 92.54%) as an off-white solid. LC / MS: mass calcd. for C18H14F3N3O: 345.11, found: 346.05 [M+H]+. 3-tert-butyl-1-(1-{[2-cyano-5-(trifluoromethyl) phenyl] methyl}-2-oxo-3,4-dihydroquinolin- 6-yl) urea To a stirred solution of 2-[(6-amino-2-oxo-3,4-dihydroquinolin-1-yl) methyl]-4- (trifluoromethyl) benzonitrile (100 mg, 0.290 mmol, 1 equiv) in DCM / Toluene (10 mL, 2 / 1) was added 2-isocyanato-2-methylpropane (114.83 mg, 1.160 mmol, 4 equiv) in portions at room temperature under air atmosphere. The resulting mixture was stirred for 3 h at 90oC under air atmosphere. Desired product could be detected by LCMS. The reaction was quenched with water (30 mL). The resulting mixture was extracted with ethyl acetate (3 x 30 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by Prep-HPLC with the following conditions to afford 3-tert-butyl-1-(1- {[2-cyano-5-(trifluoromethyl) phenyl] methyl}-2-oxo-3,4-dihydroquinolin-6-yl) urea (20.3 mg, 15.49%) as a white solid. MS (ESI): mass calcd. for C23H23F3N4O2: 444.2m / z, found 445.10 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.09 – 8.19 (m, 2H), 7.86 (d, J = 8.1 Hz, 1H), 7.55 (s, 1H), 7.33 (d, J = 2.4 Hz, 1H), 7.03 (dd, J = 8.8, 2.4 Hz, 1H), 6.77 (d, J = 8.7 Hz, 1H), 5.94 (s, 1H), 5.33 (s, 2H), 2.92 (t, J = 7.3 Hz, 2H), 2.67 (t, J = 7.2 Hz, 2H), 1.27 (s, 9H).19F NMR (282 MHz, DMSO) δ -62.00. Example 56: (S)-1-(tert-butyl)-3-(2-oxo-1-(1-(m-tolyl)ethyl)-1,2,3,4-tetrahydroquinolin-6- yl)urea (S)-6-nitro-1-(1-(m-tolyl)ethyl)-3,4-dihydroquinolin-2(1H)-one To a solution of (1R)-1-(3-methylphenyl)ethanol (300 mg, 2.203 mmol, 1 equiv) in DCM (5 mL) was added 6-nitro-3,4-dihydro-1H-quinolin-2-one (465.64 mg, 2.423 mmol, 1.1 equiv) and PPh3(577.76 mg, 2.203 mmol, 1 equiv). DEAD (383.62 mg, 2.203 mmol, 1 equiv) was added the mixture at 0 °C under a nitrogen atmosphere. The resulting mixture was stirred for 16 h at rt. The reaction mixture was quenched by water and extracted with EA (3 x 50 mL). The combined organic extracts were washed with brine (50 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford (S)-6-nitro-1-(1-(m-tolyl)ethyl)-3,4-dihydroquinolin- 2(1H)-one (310 mg, 45.35%) as a yellow solid. MS (ESI): mass calcd. for C18H18N2O3: 310.353, found: 311.10 [M+H]+. (S)-6-amino-1-(1-(m-tolyl)ethyl)-3,4-dihydroquinolin-2(1H)-one To a solution of (S)-6-nitro-1-(1-(m-tolyl)ethyl)-3,4-dihydroquinolin-2(1H)-one (200 mg, 0.644 mmol, 1 equiv) in MeOH (10 mL) was added Pd / C (30 mg). The reaction mixture was then stirred for 1 h under hydrogen atmosphere (balloon). The reaction mixture was filtered through a pad of Celite and concentrated under reduced pressure to afford (S)-6-amino-1-(1-(m- tolyl)ethyl)-3,4-dihydroquinolin-2(1H)-one (170 mg, 94.44%) as a yellow solid. MS (ESI): mass calcd. For C18H20N2O, 280.16 m / z, found 281.15 [M+H]+. (S)-1-(tert-butyl)-3-(2-oxo-1-(1-(m-tolyl)ethyl)-1,2,3,4-tetrahydroquinolin-6-yl)urea To a stirred solution of (S)-6-amino-1-(1-(m-tolyl)ethyl)-3,4-dihydroquinolin-2(1H)-one (100 mg, 0.357 mmol, 1 equiv) in DCM (5 mL) was added 2-isocyanato-2-methylpropane (176.79 mg, 1.785 mmol, 5 equiv) and TEA (144.37 mg, 1.428 mmol, 4 equiv) stirred overnight at rt. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL).The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column eluted with PE / EA (2:1) & Prep-HPLC (XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 26% B to 42% B in 10 min, 42% B; Wave Length: 254 / 220 nm; RT1(min): 8.6; Number Of Runs: 0) to afford (S)-1-(tert-butyl)-3-(2-oxo-1-(1-(m-tolyl)ethyl)-1,2,3,4- tetrahydroquinolin-6-yl)urea (20.4 mg, 15.03%) as a white solid. MS (ESI): mass calcd. for C23H29N3O2: 379.23 m / z, found 380.10 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.07 (s, 1H), 7.32 (d, J = 2.5 Hz, 1H), 7.22 (t, J = 7.5 Hz, 1H), 7.01 – 7.11 (m, 3H), 6.78 – 6.87 (m, 1H), 6.44 – 6.53 (m, 1H), 6.06 – 6.20 (m, 1H), 5.93 (s, 1H), 2.73 – 2.88 (m, 2H), 2.52 – 2.73 (m, 2H), 2.29 (s, 3H), 1.66 (d, J = 7.2 Hz, 3H), 1.26 (s, 9H). Example 57: (S)-1-(tert-butyl)-3-(3-oxo-4-(1-(m-tolyl)ethyl)-3,4-dihydro-2H-benzo[b][1,4]ox azin-7-yl)urea (S)-7-nitro-4-(1-(m-tolyl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one To a solution of (R)-1-(m-tolyl)ethan-1-ol (500 mg, 3.671 mmol, 1 equiv), 7-nitro-2H- benzo[b][1,4]oxazin-3(4H)-one (784.03 mg, 4.038 mmol, 1.1 equiv) and PPh3 (1.44 g, 5.506 mmol, 1.5 equiv) in DCM (20 mL ) was added DEAD (958.87 mg, 5.506 mmol, 1.5 equiv) under N2at 0 °C. The reaction was stirred for 16 h at rt. The mixture was diuted with EtOAc (50 mL), washed with water (30 mL) and brine (30 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column, eluted with PE / EA (3:1) to afford (S)-7-nitro-4-(1-(m-tolyl)ethyl)-2H- benzo[b][1,4]oxazin-3(4H)-one (620 mg, 54.07%) as a yellow oil. LC / MS: C17H16N2O4: 312.325, found: 313.10 [M+H]+. (S)-7-amino-4-(1-(m-tolyl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one To a solution of (S)-7-nitro-4-(1-(m-tolyl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (300 mg, 0.961 mmol, 1 equiv) in MeOH (10 mL) was added Pd / C (50 mg). The reaction mixture was then stirred for 1 h under hydrogen atmosphere (balloon). The reaction mixture was filtered through a pad of Celite and concentrated under reduced pressure to afford (S)-7-amino-4-(1-(m- tolyl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (200 mg, 73.75%) as a white solid. MS (ESI): mass calcd. for C17H18N2O2, 282.14 m / z, found 283.20 [M+H]+. (S)-1-(tert-butyl)-3-(3-oxo-4-(1-(m-tolyl)ethyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7- yl)urea To a stirred solution of (S)-7-amino-4-(1-(m-tolyl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)- one (200 mg, 0.708 mmol, 1 equiv) in DCM (10 mL) was added 2-isocyanato-2-methylpropane (351.1 mg, 3.542 mmol, 5 equiv) and TEA (215.0 mg, 2.125 mmol, 3 equiv) stirred 16 h at rt. The reaction mixture was quenched by water and extracted with EA (3 x 20 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by silica gel column eluted with PE / EA (2:1) & Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 37% B to 57% B in 10 min; Wave Length: 220 nm; RT1(min): 9.5; Number Of Runs: 2) to afford (S)-1-(tert-butyl)-3-(3-oxo-4-(1-(m-tolyl)ethyl)-3,4-dihydro-2H- benzo[b][1,4]oxazin-7-yl)urea (44.8 mg, 16.56%) as a white solid. MS (ESI): mass calcd. for C22H27N3O3, 381.21 m / z, found 382.15 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.18 (s, 1H), 7.20 – 7.28 (m, 2H), 7.10 (dd, J = 14.1, 6.8 Hz, 3H), 6.62 (dd, J = 8.9, 2.4 Hz, 1H), 6.55 (d, J = 8.8 Hz, 1H), 6.09 (q, J = 7.2 Hz, 1H), 5.94 (s, 1H), 4.57 – 4.75 (m, 2H), 2.30 (s, 3H), 1.70 (d, J = 7.2 Hz, 3H), 1.25 (s, 9H). Example 58: 3-tert-butyl-1-{1-[(1S)-1-(2-fluorophenyl)ethyl]-2-oxo-3,4-dihydroquinolin-6-y l}ure 1-[(1S)-1-(2-fluorophenyl)ethyl]-6-nitro-3,4-dihydroquinolin-2-one To a solution of (1R)-1-(2-fluorophenyl)ethanol (500 mg, 3.567 mmol, 1 equiv) and 6- nitro-3,4-dihydro-1H-quinolin-2-one (685.57 mg, 3.567 mmol, 1 equiv) in DCM (20 mL) was added triphenylphosphine (935.71 mg, 3.567 mmol, 1 equiv). The reaction was stirred at rt under N2 for 0.5 hour. To the above mixture was added DEAD (621.29 mg, 3.567 mmol, 1 equiv) dropwise at 0oC. The reaction was stirred at rt under N2for 3h. Quenched with water (20 mL) and extracted with EA (3 x 30 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 1-[(1S)-1-(2-fluorophenyl)ethyl]-6-nitro-3,4- dihydroquinolin-2-one (723 mg, 64.48%) as a white solid. MS (ESI): mass calcd for C17H15FN2O3: 314.11 m / z, found 315.00[M+H]+. 6-amino-1-[(1S)-1-(2-fluorophenyl)ethyl]-3,4-dihydroquinolin-2-one To a solution of 1-[(1S)-1-(2-fluorophenyl)ethyl]-6-nitro-3,4-dihydroquinolin-2-one (710 mg, 2.259 mmol, 1 equiv) in methanol (20 mL) was added Pd / C (710 mg). The resulting mixture was stirred for 1 h at room temperature under hydrogen atmosphere. Desired product could be detected by LCMS. The resulting mixture was filtered, the filter cake was washed with MeOH (3 x 10 mL). The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 6-amino-1-[(1S)-1-(2- fluorophenyl)ethyl]-3,4-dihydroquinolin-2-one (420 mg, 65.39%) as a black liquid. MS (ESI): mass calcd for C17H17FN2O: 284.13m / z, found 285.10 [M+H]+. 3-tert-butyl-1-{1-[(1S)-1-(2-fluorophenyl)ethyl]-2-oxo-3,4-dihydroquinolin-6-yl}urea To a solution of 6-amino-1-[(1S)-1-(2-fluorophenyl)ethyl]-3,4-dihydroquinolin-2-one (200 mg, 0.703 mmol, 1 equiv) and 2-isocyanato-2-methylpropane (139.46 mg, 1.406 mmol, 2 equiv) in DCM (20 mL,) was added TEA (213.54 mg, 2.109 mmol, 3.00 equiv). The reaction was stirred at rt for 16h. Quenched with water (20 mL) and extracted with EA (3 x 30 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by preparative HPLC using a XBridge Prep OBD C18 Column150 mm x 30 mm x 5 μm (eluent: 17% to 42% (v / v) CH3CN and H2O with 10mmol / L NH4HCO3) to afford the title compound 3-tert-butyl-1-{1-[(1S)-1-(2-fluorophenyl)ethyl]-2-oxo-3,4- dihydroquinolin-6-yl}urea (21.2 mg, 7.85%) as a white solid. LC / MS (ESI): mass calcd. for C22H26FN3O2:383.20 m / z, found:384.00 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.07 (s, 1H), 7.46 – 7.55 (m, 1H), 7.21 – 7.33 (m, 2H), 7.17 (m, 1H), 7.06 (m, 1H), 6.93 (m, 1H), 6.81 (m, 1H), 6.00 (m, 1H), 5.89 (s, 1H), 2.69 – 2.79 (m, 2H), 2.40 – 2.50 (m, 2H), 1.76 (s, 3H), 1.26 (s, 9H).19F NMR (376 MHz, DMSO) δ -116.16. Example 59: 1-(tert-butyl)-3-(1-(2-cyano-3-(trifluoromethyl)benzyl)-2-oxo-1,2,3,4-tetrahydr oquinolin-6-yl)urea Synthetic Scheme

[0013] 2-bromo-1-(bromomethyl)-3-(trifluoromethyl)benzene To a solution of [2-bromo-3-(trifluoromethyl)phenyl]methanol (1.5 g, 5.882 mmol, 1 equiv) in DCM (10 mL) was added phosphorus tribromide (3.18 g, 11.764 mmol, 2 equiv) at 0oC. The reaction was stirred at rt for 2 hours. Quenched with water (10 mL) and extracted with EA (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. This resulted in 2-bromo-1-(bromomethyl)-3- (trifluoromethyl)benzene (1.83 g, 97.86%) as a yellow oil. MS (ESI): mass calcd. for C8H5Br2F3: 317.93m / z, found 318.90 [M+H]+. 1-(2-bromo-3-(trifluoromethyl)benzyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one To a solution of 6-nitro-3,4-dihydro-1H-quinolin-2-one (426.14 mg, 2.217 mmol, 1 equiv) in DMF (10 mL) was added K2CO3 (617.40 mg, 4.434 mmol, 2 equiv) and 2-bromo-1- (bromomethyl)-3-(trifluoromethyl)benzene (705 mg, 2.217 mmol, 1 equiv). The reaction was stirred at rt for 1 hour. Quenched with water (20 mL) and extracted with EA (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 1-{[2-bromo-3-(trifluoromethyl)phenyl]methyl}-6-nitro-3,4-dihydroquinolin-2-one (500 mg, 52.54%) as a white solid. MS(ESI): mass calcd. for C17H12BrF3N2O3: 429.19 m / z, found 428.95 [M+H]+. 2-((6-nitro-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl)-6-(trifluoromethyl)benzonitrile To a solution of 1-{[2-bromo-3-(trifluoromethyl)phenyl]methyl}-6-nitro-3,4- dihydroquinolin-2-one (250 mg, 0.582 mmol, 1 equiv) in DMF (10 mL) was added Zn(CN)2(82.07 mg, 0.698 mmol, 1.2 equiv), Zn (19.04 mg, 0.291 mmol, 0.5 equiv), BrettPhos (62.53 mg, 0.116 mmol, 0.2 equiv) and BrettPhos Pd G3 (158.41 mg, 0.175 mmol, 0.3 equiv). The reaction was stirred at 120 °C under N2 for 1h. Quenched with water (10 mL) and extracted with EA (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0- 100%) to give 2-[(6-nitro-2-oxo-3,4-dihydroquinolin-1-yl)methyl]-6- (trifluoromethyl)benzonitrile (90 mg, 41.17%) as a white solid. MS (ESI): mass calcd. for C18H12F3N3O3: 375.31 m / z, found:370.15 [M+H]+. 2-((6-amino-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl)-6-(trifluoromethyl)benzonitrile To a solution of 2-[(6-nitro-2-oxo-3,4-dihydroquinolin-1-yl)methyl]-6- (trifluoromethyl)benzonitrile (140 mg, 0.373 mmol, 1 equiv) in HOAc (10 mL) was added zinc (243.89 mg, 3.730 mmol, 10 equiv). The reaction was stirred at rt for 1 hour. Quenched with water (10 mL) and extracted with EA (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 2-[(6-amino-2-oxo-3,4- dihydroquinolin-1-yl)methyl]-6-(trifluoromethyl)benzonitrile (90 mg, 69.87%) as a white solid. MS (ESI): mass calcd. for C18H14F3N3O: 345.33m / z, found:368.10 [M+Na]+. 1-(tert-butyl)-3-(1-(2-cyano-3-(trifluoromethyl)benzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6- yl)urea To a solution of 2-[(6-amino-2-oxo-3,4-dihydroquinolin-1-yl)methyl]-6- (trifluoromethyl)benzonitrile (90 mg, 0.261 mmol, 1 equiv) in DCM (10 mL) was added 2- isocyanato-2-methylpropane (103.35 mg, 1.044 mmol, 4 equiv) and TEA (79.12 mg, 0.783 mmol, 3 equiv). The reaction was stirred at rt for 1 day. Quenched with water (20 mL) and extracted with DCM (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by preparative HPLC using a XBridge Prep OBD C18 Column, 30*150 mm, 5μm column (eluent: 30% to 50% (v / v) CH3CN and H2O with 10mmol / L NH4HCO3) to afford the title compound 3-tert-butyl-1-(1-{[2-cyano-3- (trifluoromethyl)phenyl]methyl}-2-oxo-3,4-dihydroquinolin-6-yl)urea (51 mg, 44.03%) as a white solid. MS (ESI): mass calcd. for C23H23F3N4O2: 444.46m / z, found:445.15 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.04 - 8.29 (m, 1H), 7.89 - 8.00 (m, 1H), 7.73 - 8.00 (m, 1H), 7.45 – 7.55 (m, 1H), 7.35 – 7.45 (m, 1H), 6.88 – 7.09 (m, 1H), 6.67 – 6.80 (m, 1H), 5.82 – 6.07 (m, 1H), 5.20 – 5.50 (m, 2H), 2.86 – 3.07 (m, 2H), 2.60 – 2.78 (m, 2H), 1.15 – 1.38 (m, 9H).19F NMR (376 MHz, DMSO) δ (ppm): -60.5758. Example 60: (S)-3-tert-butyl-1-(2-oxo-1-{1-[3-(trifluoromethyl)phenyl]ethyl}-3,4-dihydroqu inolin-6-yl)urea 6-nitro-1-[(1S)-1-[3-(trifluoromethyl)phenyl]ethyl]-3,4-dihydroquinolin-2-one To a solution of (1R)-1-[3-(trifluoromethyl)phenyl]ethanol (500 mg, 2.629 mmol, 1 equiv) and 6-nitro-3,4-dihydro-1H-quinolin-2-one (505.28 mg, 2.629 mmol, 1 equiv) in DCM (20 mL) was added triphenylphosphine (689.64 mg, 2.629 mmol, 1 equiv). The reaction was stirred at rt under N2for 0.5 hour. To the above mixture was addedDEAD (457.91 mg, 2.629 mmol, 1 equiv) dropwise at 0oC. The reaction was stirred at rt under N2 for 3h. Quenched with water (30 mL) and extracted with EA (3 x 30 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 6-nitro-1-[(1S)-1-[3-(trifluoromethyl)phenyl]ethyl]-3,4- dihydroquinolin-2-one (285 mg, 29.75%) as a white solid.MS (ESI): mass calcd. for C18H15F3N2O3: 364.10 m / z, found 365.11[M+H]+. 6-amino-1-[(1S)-1-[3-(trifluoromethyl)phenyl]ethyl]-3,4-dihydroquinolin-2-one To a solution of 6-nitro-1-[(1S)-1-[3-(trifluoromethyl)phenyl]ethyl]-3,4-dihydroquinolin-2-one (285 mg, 0.782 mmol, 1 equiv) in methanol (3 mL) was added Pd / C (150 mg). The reaction was stirred at rt under H2 for 1h. The resulting mixture was stirred for 1 h at room temperature under hydrogen atmosphere. Desired product could be detected by LCMS. The resulting mixture was filtered, the filter cake was washed with MeOH (3 x 10 mL). The filtrate was concentrated under reduced pressure.The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 6-amino-1-[(1S)-1-[3-(trifluoromethyl)phenyl]ethyl]-3,4-dihydroquinolin-2- one (225 mg, 86.03%) as a white solid. MS (ESI): mass calcd for C18H17F3N2O: 334.13 m / z, found 335.15 [M+H]+. (S)-3-tert-butyl-1-(2-oxo-1-{1-[3-(trifluoromethyl)phenyl]ethyl}-3,4-dihydroquinolin-6- yl)urea To a solution of 6-amino-1-[(1S)-1-[3-(trifluoromethyl)phenyl]ethyl]-3,4-dihydroquinolin-2-one (200 mg, 0.598 mmol, 1 equiv) and 2-isocyanato-2-methylpropane (177.90 mg, 1.794 mmol, 3 equiv) in DCM (3 mL) was added TEA (181.60 mg, 1.794 mmol, 3 equiv). The reaction was stirred at rt for 16h. Quenched with water (10 mL) and extracted with EA (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered and concentrated. The residue was purified by preparative HPLC using a XBridge Prep OBD C18150 mm x 30 mm x 5 μm column (eluent: 26% to 42% (v / v) CH3CN and H2O with 10mmol / L NH4HCO3) to afford the title compound (S)-3-tert-butyl-1-(2-oxo-1-{1-[3-(trifluoromethyl)phenyl]ethyl}-3,4- dihydroquinolin-6-yl)urea (20.1 mg, 7.73%) as a white solid. LC / MS (ESI): mass calcd. for C23H26F3N3O2:433.20 m / z, found:432.05 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.10 (s, 1H), 7.52 – 7.65 (m, 4H), 7.33 (s, 1H), 6.90 (m, 1H), 6.52 (m, 1H), 6.08 (m, 1H), 5.92 (s, 1H), 2.79-2.89 (m, 2H), 2.52 – 2.66 (m, 2H), 1.74 (m, 3H), 1.26 (s, 9H).19F NMR (282 MHz, DMSO) δ -60.93. Example 61: (S)-1-(tert-butyl)-3-(1-(1-(2-cyanophenyl)ethyl)-2-oxo-1,2,3,4-tetrahydroquino lin-6-yl)urea (S)-1-(1-(2-bromophenyl)ethyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one To a solution of (1R)-1-(2-bromophenyl)ethanol (1 g, 4.974 mmol, 1 equiv) in THF (10 mL) was added 6-nitro-3,4-dihydro-1H-quinolin-2-one (1.05 g, 5.471 mmol, 1.1 equiv), PPh3(1.30 g, 4.974 mmol, 1 equiv) at rt. The resulting mixture was stirred at 0 °C under a nitrogen atmosphere, which was added DEAD (0.87 g, 4.974 mmol, 1 equiv). The resulting mixture was extracted with EA (3 x 100 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by flash chromatography (PE / EA=3:1) to afford (S)-1-(1-(2- bromophenyl)ethyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one (1.2 g, 64.30%) as a yellow oil. MS (ESI): mass calcd. for C17H15BrN2O3: 374.03, found: 375.05[M+H]+. (S)-2-(1-(6-nitro-2-oxo-3,4-dihydroquinolin-1(2H)-yl)ethyl)benzonitrile A solution of 1-[(1S)-1-(2-bromophenyl)ethyl]-6-nitro-3,4-dihydroquinolin-2-one (400 mg, 1.066 mmol, 1 equiv) in dimethylformamide (10 mL) was added Zn(CN)2 (250.35 mg, 2.132 mmol, 2.0 equiv) and Pd(PPh3)4 (123.19 mg, 0.107 mmol, 0.1 equiv) at rt. The resulting mixture was stirred for overnight at 110 °C. The resulting mixture was extracted with EA (3 x 10 mL). The combined organic layers were washed with NaCl (3x5 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (3 / 1) to afford (S)-2-(1-(6-nitro-2-oxo-3,4- dihydroquinolin-1(2H)-yl)ethyl)benzonitrile (78 mg, 22.77%) as an off-white solid. MS (ESI): mass calcd. for C18H15N3O3, 321.11 m / z, found 322.20 [M+H]+. (S)-2-(1-(6-amino-2-oxo-3,4-dihydroquinolin-1(2H)-yl)ethyl)benzonitrile solution of (S)-2-(1-(6-nitro-2-oxo-3,4-dihydroquinolin-1(2H)-yl)ethyl)benzonitrile (70 mg, 0.218 mmol, 1 equiv) in MeOH (5 mL) / H2O (0.5 mL) was added Fe (121.65 mg, 2.180 mmol, 10 equiv) and NH4Cl (116.52 mg, 2.180 mmol, 10 equiv) at rt. The resulting mixture was stirred for 1 h at 60 °C. The precipitated solids were collected by filtration and washed with MeOH (3 x 5 mL). The aqueous layer was extracted with DCM (3 x 5 mL). The organic layer was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (2:1) to afford (S)-2-(1-(6-amino-2-oxo-3,4- dihydroquinolin-1(2H)-yl)ethyl)benzonitrile (60 mg, 94.53%) as a yellow solid. MS (ESI): mass calcd. for C18H17N3O, 291.14 m / z, found 292.20 [M+H]+. (S)-1-(tert-butyl)-3-(1-(1-(2-cyanophenyl)ethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea A solution of (S)-2-(1-(6-amino-2-oxo-3,4-dihydroquinolin-1(2H)-yl)ethyl)benzonitrile (70 mg, 0.240 mmol, 1 equiv) in DCM (5 mL) was added 2-isocyanato-2-methylpropane (119.09 mg, 1.200 mmol, 5.0 equiv) and TEA (97.25 mg, 0.960 mmol, 4.0 equiv) at rt. The resulting mixture was stirred for overnight at TR. The resulting mixture was extracted with EA (5 mL x 3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product 50 mg was purified by Prep-HPLC with the following conditions (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water(10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 30% B to 54% B in 7 min; Wave Length: 220 nm; RT1(min): 6.5; Number Of Runs: 0 ) to afford (S)-1-(tert-butyl)-3-(1-(1-(2-cyanophenyl)ethyl)- 2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea (22.5 mg, 23.93%) as white solid. MS (ESI):mass calcd.C23H26N4O2 for :390.21 m / z, found 391.20 [M+H]+.1H NMR (400 MHz, Chloroform-d) δ 7.72 (d, J = 7.9 Hz, 1H), 7.56 – 7.66 (m, 2H), 7.21 – 7.32 (m, 1H), 7.18 – 7.20 (m, 1H),7.09 – 7.12(m,1H), 6.79 – 6.92 (m, 1H), 6.61 – 6.74 (m, 1H), 5.87 – 6.02 (m, 2H), 2.92 – 3.01 (m, 1H), 2.71 – 2.83 (m, 1H), 2.53 – 2.69 (m, 1H), 2.42 – 2.53 (m, 1H), 1.96 (d, J = 7.1 Hz, 3H), 1.35 – 1.40 (m, 9H). Example 62: (S)-1-(tert-butyl)-3-(3-oxo-4-(1-(3-(trifluoromethyl)phenyl)ethyl)-3,4-dihydro- 2H-benzo[b][1,4]oxazin-7-yl)urea (S)-7-nitro-4-(1-(3-(trifluoromethyl)phenyl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one To a solution of (1R)-1-[3-(trifluoromethyl)phenyl]ethanol (500 mg, 2.629 mmol, 1 equiv), 7-nitro-2,4-dihydro-1,4-benzoxazin-3-one (510.47 mg, 2.629 mmol, 1 equiv) and PPh3 (1034.46 mg, 3.944 mmol, 1.5 equiv) in DCM (10 mL). The reaction was stirred at rt under N2 for 0.5 hour. To the above mixture was added DEAD (686.86 mg, 3.944 mmol, 1.5 equiv) dropwise at 0oC. The resulting mixture was stirred for additional 1h at rt. Quenched with water (20 mL) and extracted with DCM (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 7-nitro-4-[(1S)-1-[3- (trifluoromethyl)phenyl]ethyl]-2H-1,4-benzoxazin-3-one (550 mg, 57.11%) as a yellow solid. MS (ESI): mass calcd. for C17H13F3N2O4: 366.30m / z, found 367.00 [M+H]+. (S)-7-amino-4-(1-(3-(trifluoromethyl)phenyl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one To a solution of 7-nitro-4-[(1S)-1-[3-(trifluoromethyl)phenyl]ethyl]-2H-1,4-benzoxazin- 3-one (500 mg, 1.365 mmol, 1 equiv) in MeOH / H2O (16.5 mL, 10:1) was added Fe (762.29 mg, 13.650 mmol, 10 equiv) and NH4Cl (730.15 mg, 13.650 mmol, 10 equiv). The reaction was stirred at 80oC for 1 hour. The reaction was quenched with water at rt. After filtration, the filter cake was washed with EA (3 x 20 mL). The filtrate was added water (20 mL) and extracted with EA (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. This resulted in 7-amino-4-[(1S)-1-[3-(trifluoromethyl)phenyl]ethyl]- 2H-1,4-benzoxazin-3-one (450 mg, 98.02%) as a yellow soild. MS (ESI): mass calcd. for C17H15F3N2O2: 336.31m / z, found 337.15 [M+H]+. (S)-1-(tert-butyl)-3-(3-oxo-4-(1-(3-(trifluoromethyl)phenyl)ethyl)-3,4-dihydro-2H- benzo[b][1,4]oxazin-7-yl)urea To a solution of 7-amino-4-[(1S)-1-[3-(trifluoromethyl)phenyl]ethyl]-2H-1,4- benzoxazin-3-one (150 mg, 0.446 mmol, 1 equiv) in DCM (10 mL) was added 2-isocyanato-2- methylpropane (176.86 mg, 1.784 mmol, 4 equiv) and TEA (135.40 mg, 1.338 mmol, 3 equiv). The reaction was stirred at rt for 1 day. Quenched with water (20 mL) and extracted with EA (3 x 20 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by preparative HPLC using a XBridge Prep OBD C18 Column, 30*150 mm, 5μm column (eluent: 35% to 60% (v / v) CH3CN and H2O with 10mmol / L NH4HCO3) to afford the title compound 3-tert-butyl-1-{3-oxo-4-[(1S)-1-[3- (trifluoromethyl)phenyl]ethyl]-2H-1,4-benzoxazin-7-yl}urea (50.1 mg, 25.80%) as a white solid. MS (ESI): mass calcd. for C22H24F3N3O3: 435.45 m / z, found:436.20 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.10 – 8.31 (m, 1H), 7.45 – 7.80 (m, 4H), 7.07 – 7.38 (m, 1H), 6.44 – 6.85 (m, 2H), 6.01 – 6.19 (m, 1H), 5.79 – 6.01 (m, 1H), 4.50 – 4.90 (m, 2H), 1.70 – 1.90 (m, 3H), 1.21 – 1.32 (m, 9H).19F NMR (376 MHz, DMSO) δ (ppm): -60.8904. Example 63: 5-benzyl-6-oxo-7,8-dihydro-5H-naphthalen-2-yl N-tert-butylcarbamate Synthetic Scheme 1-benzyl-6-methoxy-3,4-dihydroquinolin-2-one To a solution of 6-methoxy-3,4-dihydro-1H-quinolin-2-one (473.5 mg, 2.672 mmol, 1 equiv) and benzyl bromide (1142.56 mg, 6.680 mmol, 2.5 equiv) in dimethylformamide (25 mL) was added Cs2CO3 (2619.92 mg, 8.016 mmol, 3 equiv). The reaction was stirred at rt for 3h. Quenched with water (50 mL) and extracted with EA (3 x 50 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give tert-butyl 1- benzyl-6-methoxy-3,4-dihydroquinolin-2-one (640 mg, 89.60%) as a white solid.MS (ESI): mass calcd. for C17H17NO2: 267.13 m / z, found 268.10[M+H]+. 1-benzyl-6-hydroxy-3,4-dihydroquinolin-2-one To a solution of 1-benzyl-6-methoxy-3,4-dihydroquinolin-2-one (620 mg, 2.319 mmol, 1 equiv) in DCM (8 mL) was added boron tribromide (7 mL) at -78 °C under nitrogen atmosphere. The reaction was stirred at -78 °C for 3h. Quenched with water (50 mL) and extracted with EA (3 x 50 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with EA / PE (0-100%) to give 1-benzyl-6-hydroxy-3,4-dihydroquinolin-2-one (312 mg, 53.11%) as a black solid. MS (ESI): mass calcd for C16H15NO2: 253.11 m / z, found 253.95[M+H]+. 5-benzyl-6-oxo-7,8-dihydro-5H-naphthalen-2-yl N-tert-butylcarbamate To a solution of 1-benzyl-6-hydroxy-3,4-dihydro-1H-naphthalen-2-one (132 mg, 0.523 mmol, 1 equiv) and 2-isocyanato-2-methylpropane (103.32 mg, 1.042 mmol, 2 equiv) in DCM (2 mL) was added TEA (158.20 mg, 1.563 mmol, 3 equiv). The reaction was stirred at rt for 16h. Quenched with water (10 mL) and extracted with EA (3 x 10 mL). The combined extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by preparative HPLC using a XBridge Prep OBD C18150 mm x 30 mm x 5 μm column (eluent: 17% to 42% (v / v) CH3CN and H2O with 10mmol / L NH4HCO3) to afford the title compound 5-benzyl-6-oxo-7,8-dihydro-5H-naphthalen-2-yl N-tert-butylcarbamate (50.2 mg, 27.27%) as a white solid. LC / MS (ESI): mass calcd. for C21H24N2O3:352.18 m / z, found:353.05 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 7.50 (s, 1H), 7.22 – 7.37 (m, 5H), 6.97 (m, 1H), 6.76 – 6.91 (m, 2H), 5.13 (s, 2H), 2.89-3.01 (m, 2H), 2.69-2.73 (m, 2H), 1.25 (s, 9H). Example 64: 1-(tert-butyl)-3-(1-(cyclohexylmethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)u rea 1-(cyclohexylmethyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one To a stirred solution of 6-nitro-3,4-dihydro-1H-quinolin-2-one (300 mg, 1.561 mmol, 1.0 equiv) in DMF (15 mL) was added Cs2CO3 (1.53 g, 4.683 mmol, 3.0 equiv) and (bromomethyl)cyclohexane (276.44 mg, 1.561 mmol, 1 equiv) at rt and stirred for overnight. The reaction progress was monitored by LCMS. After completion of reaction, the resulting mixture was extracted with EA (3 x 30 mL). The combined organic layers were washed with water (3 x2 0 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (PE / EA =3:1) to afford 1-(cyclohexylmethyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one (310 mg, 68.87%) as a yellow solid. MS (ESI): mass calcd. for C16H20N2O3: 288.15 m / z, found 289.15 [M +H]+. 6-amino-1-(cyclohexylmethyl)-3,4-dihydroquinolin-2(1H)-one To a solution of 1-(cyclohexylmethyl)-6-nitro-3,4-dihydroquinolin-2-one (100 mg, 0.347 mmol, 1 equiv) in methanol (5 mL) was added Pd / C (30 mg) under nitrogen atmosphere. The mixture was hydrogenated at room temperature for 50 min under hydrogen atmosphere using a hydrogen balloon, filtered through a Celite pad and concentrated under reduced pressure. This resulted in 6-amino-1-(cyclohexylmethyl)-3,4-dihydroquinolin-2(1H)-one as a white solid. MS (ESI): mass calcd. for C16H22N2O: 258.17 m / z, found 259.30 [M +H]+. 1-(tert-butyl)-3-(1-(cyclohexylmethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea A solution of 6-amino-1-(cyclohexylmethyl)-3,4-dihydroquinolin-2(1H)-one (50 mg, 0.194 mmol, 1 equiv), triethylamine (58.75 mg, 0.582 mmol, 3 equiv) and 2-isocyanato-2- methylpropane (57.55 mg, 0.582 mmol, 3 equiv) in DCM (5 mL) was stirred for overnight at rt. The residue was purified by silica gel column chromatography (PE / EA = 2:1) to afford crude products. The residue was purified by Prep-HPLC with the following conditions (Column: XBridge Prep OBD C18 Column, 30*150 mm, 5μm; Mobile Phase A: Water (10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 26% B to 50% B in 9 min, 50% B; Wave Length: 254 / 220 nm; RT1(min): 8.9;) to afford 1-(tert-butyl)-3-(1- (cyclohexylmethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)urea (26.5 mg, 38.18%) as a white solid. MS (ESI):mass calcd. for C21H31N3O2: 357.24 m / z, found 358.25 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.14 (s, 1H), 7.28 (d, J = 2.4 Hz, 1H), 7.12 (dd, J = 8.8, 2.5 Hz, 1H), 6.99 (d, J = 8.8 Hz, 1H), 5.94 (s, 1H), 3.76 (d, J = 6.9 Hz, 2H), 2.77 (dd, J = 8.8, 5.8 Hz, 2H), 2.47 (d, J = 6.3 Hz, 2H), 1.55 - 1.64 (m, 6H), 1.28 (s, 9H), 1.09 (t, J = 9.5 Hz, 3H), 0.95 (t, J = 11.2 Hz, 2H). Example 65:1-(1-benzyl-7-fluoro-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-(tert-butyl)urea Synthetic Scheme 7-fluoro-6-nitro-3,4-dihydroquinolin-2(1H)-one To a solution of 7-fluoro-3,4-dihydro-1H-quinolin-2-one (526 mg, 3.185 mmol, 1 equiv) in H2SO4(3.2 mL) was added HNO3(200.6 mg,3.185 mmol, 1.0 equiv)at 0 °C.The resulting mixture was stirred at 0 °C until the starting material was totally consumed by LCMS, the reaction mixture was quenched by water and extracted with EA (3 x 20 mL).The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by flash chromatography (PE / EA = 3:1) to afford 7-fluoro-6-nitro-3,4-dihydro-1H-quinolin-2-one (300 mg, 35.30%) as a yellow solid. MS (ESI): mass calcd. for C9H7FN2O3, 210.04 m / z, found 211.10 [M+H]+. 1-benzyl-7-fluoro-6-nitro-3,4-dihydroquinolin-2(1H)-one To a solution of 7-fluoro-6-nitro-3,4-dihydro-1H-quinolin-2-one (300 mg, 1.427 mmol, 1 equiv) in DMF (8 mL) was added K2CO3(591.8 mg, 4.282 mmol, 3 equiv) and benzyl bromide(488.3 mg, 2.855 mmol, 2 equiv). The resulting mixture was placed at rt and stirred overnight until the starting material was totally consumed by LCMS. The reaction mixture was quenched by water and extracted with EA (3*20 mL).The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under vacuum to yield a crude product which was directly purified by flash chromatography (0-100% ethyl acetate / petroleum ether) to afford 1-benzyl-7-fluoro-6-nitro-3,4-dihydroquinolin-2-one (250 mg, 57.56%) as a white solid.MS (ESI): mass calcd. for C16H13FN2O3, 300.09 m / z, found 301.10 [M+H]+. 6-amino-1-benzyl-7-fluoro-3,4-dihydroquinolin-2(1H)-one To a solution of 1-benzyl-7-fluoro-6-nitro-3,4-dihydroquinolin-2-one (250 mg, 0.833 mmol, 1 equiv) in MeOH (10 mL) was added Pd / C (30 mg). The mixture was hydrogenated at room temperature for 50 min under hydrogen atmosphere using a hydrogen balloon, then filtered through a Celite pad and concentrated under reduced pressure to afford 6-amino-1-benzyl-7- fluoro-3,4-d...

Claims

We claim:

1. A compound of Formula (I):or a pharmaceutically acceptable salt thereof, wherein: A is (C6-C10)aryl, 5- to 10-membered heteroaryl, (C3-C8)cycloalkyl, or 4- to 7-membered heterocycloalkyl; n is 0, 1, 2, 3, 4, or 5; R1is independently for each occurrence (C1-C6)alkyl, (C2-C6)alkynyl, (C2-C6)alkenyl, (C3- C8)cycloalkyl, (C3-C8)cycloalkoxy, (C6-C10)aryl, (C6-C10)aryloxy, (C6-C10)aryl(C1-C6)alkyl, 4- to 7-membered heterocycloalkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl, halo, cyano, amino, formyl, carboxy, or alkoxycarbonyl, wherein (C1-C6)alkyl, (C2-C6)alkynyl, (C2-C6)alkenyl, (C3-C8)cycloalkyl, C3-C8)cycloalkoxy, (C6-C10)aryl, (C6-C10)aryloxy, (C6-C10)aryl(C1-C6)alkyl, (C1-C6)alkoxy, (C1- C6)alkoxy(C1-C6)alkyl, and 4- to 7-membered heterocycloalkyl are each optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, 4- to 7-membered heterocycloalkyl, 5- to 6- membered heteroaryl, (C1-C6)alkoxy, (C1-C6)haloalkoxy, (C1-C6)fluoroalkoxy, 5- to 6-membered heteroaryloxy, or two vicinal occurrences of R1taken together with the atoms to which they are attached form a fused 5- to 7-membered cycloalkyl, 5- to 7-membered heterocycloalkyl ring, 5- to 6- membered heteroaryl ring or phenyl ring, any of which is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1- C6)alkyl, (C1-C6)haloalkyl (C3-C8)cycloalkyl, and (C1-C6)alkoxy; Q is N or CR2c;R2a, R2b, and R2c, are each independently hydrogen, halo, cyano, (C1-C6)alkyl, or (C3- C8)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; R3is (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C6)alkyl), (C6-C10)aryl, (C6- C10)aryl(C1-C6)alkyl), or 4- to 7-membered heterocycloalkyl; each of which is optionally substituted with one or more substituents independently selected from halo, cyano, (C1- C6)haloalkyl, hydroxy, (C1-C6)alkoxy(C1-C6)alkyl, and (C1-C6)alkoxy; X and Z are independently NR4, C(R5)2, or O; R4and R5independently for each occurrence hydrogen or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy, or when Z is NR4, R3and R4taken together with the nitrogen to which they are attached form a 4- to 7-member heterocycloalkyl optionally substituted with one or more (C1-C6)alkyl or halo; L is (C1-C6)alkylene optionally substituted with one or more substituents independently selected from halo, hydroxy, C1-C6)alkoxy, and cyano; W represents: –C(R6)2–C(R7)2–, –C(R7)2–, –O–C(R8)2–, –C(R8)2–O–, –C(R8)2–NR9–, –N=C(R10) –, or –O–; and R6, R7, R8, R9and R10are independently for each occurrence hydrogen, (C1-C6)alkyl,or NH2, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, cyano, hydroxy, (C1-C6)alkoxy(C1-C6)alkyl, and (C1-C6)alkoxy.

2. A compound of Formula (I):or a pharmaceutically acceptable salt thereof, wherein: A is (C6-C10)aryl or 5- to 10-membered heteroaryl; n is 0, 1, 2, 3, 4, or 5; R1is independently for each occurrence (C1-C6)alkyl, (C3-C8)cycloalkyl, 4- to 7- membered heterocycloalkyl, (C1-C6)alkoxy, halo, cyano, formyl, carboxy, or alkoxycarbonyl, wherein (C1-C6)alkyl, (C3-C8)cycloalkyl, (C1-C6)alkoxy, and 4- to 7-membered heterocycloalkyl are each optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, and (C1-C6)alkoxy, or two vicinal occurrences of R1taken together with the atoms to which they are attached form a fused 5- to 7-membered cycloalkyl or 5- to 7-membered heterocycloalkyl ring, either of which is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, and (C1-C6)alkoxy; Q is N or CR2c; R2a, R2b, and R2c, are each independently hydrogen, halo, cyano, or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; R3is (C1-C6)alkyl optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; X and Z are independently NR4, C(R5)2, or O; R4and R5independently for each occurrence hydrogen or (C1-C6)alkyl, wherein (C1- C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; L is (C1-C6)alkylene optionally substituted with one or more substituents independently selected from halo, hydroxy, C1-C6)alkoxy, and cyano; W represents: –C(R6)2–C(R7)2–, –C(R7)2–, –O–C(R8)2–, –C(R8)2–O–, –C(R8)2–NR9–,–N=C(R10) –, or –O–; and R6, R7, R8, R9and R10are independently for each occurrence hydrogen or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy.

3. A compound of Formula (II):or a pharmaceutically acceptable salt thereof, wherein A is (C6-C10)aryl, 5- to 10-membered heteroaryl, (C3-C8)cycloalkyl, or 4- to 7-membered heterocycloalkyl; n is 0, 1, 2, 3, 4, or 5; R1is independently for each occurrence (C1-C6)alkyl, (C2-C6)alkynyl, (C2-C6)alkenyl, (C3- C8)cycloalkyl, (C3-C8)cycloalkoxy, (C6-C10)aryl, (C6-C10)aryloxy, (C6-C10)aryl(C1-C6)alkyl, 4- to 7-membered heterocycloalkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl, halo, cyano, amino, formyl, carboxy, or alkoxycarbonyl, wherein (C1-C6)alkyl, (C2-C6)alkynyl, (C2-C6)alkenyl, (C3-C8)cycloalkyl, C3-C8)cycloalkoxy, (C6-C10)aryl, (C6-C10)aryloxy, (C6-C10)aryl(C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl, and 4- to 7-membered heterocycloalkyl are each optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, 4- to 7-membered heterocycloalkyl, 5- to 6- membered heteroaryl, (C1-C6)alkoxy, (C1-C6)haloalkoxy, (C1-C6)fluoroalkoxy, 5- to 6-membered heteroaryloxy, or two vicinal occurrences of R1taken together with the atoms to which they are attached form a fused 5- to 7-membered cycloalkyl, 5- to 7-membered heterocycloalkyl ring, 5- to 6- membered heteroaryl ring or phenyl ring, any of which is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C1-C6)haloalkyl (C3-C8)cycloalkyl, and (C1-C6)alkoxy;Q is N or CR2c; R2a, R2b, and R2c, are each independently hydrogen, halo, cyano, (C1-C6)alkyl, or (C3- C8)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; R3is (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C6)alkyl), (C6-C10)aryl, (C6- C10)aryl(C1-C6)alkyl), or 4- to 7-membered heterocycloalkyl; each of which is optionally substituted with one or more substituents independently selected from halo, cyano, (C1- C6)haloalkyl, hydroxy, (C1-C6)alkoxy(C1-C6)alkyl, and (C1-C6)alkoxy; X and Z are independently NR4, C(R5)2, or O; R4and R5independently for each occurrence hydrogen or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy, or when Z is NR4, R3and R4taken together with the nitrogen to which they are attached form a 4- to 7-member heterocycloalkyl optionally substituted with one or more (C1-C6)alkyl or halo; L is (C1-C6)alkylene optionally substituted with one or more substituents independently selected from halo, hydroxy, C1-C6)alkoxy, and cyano; W represents: –C(R6)2–C(R7)2–, –C(R7)2–, –O–C(R8)2–, –C(R8)2–O–, –C(R8)2–NR9–, –N=C(R10) –, or –O–; and R6, R7, R8, R9and R10are independently for each occurrence hydrogen, (C1-C6)alkyl,or NH2, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, cyano, hydroxy, (C1-C6)alkoxy(C1-C6)alkyl, and (C1-C6)alkoxy.

4. A compound of Formula (II):or a pharmaceutically acceptable salt thereof, wherein A is (C6-C10)aryl or 5- to 10-membered heteroaryl; n is 0, 1, 2, 3, 4 or 5; R1is independently for each occurrence (C1-C6)alkyl, (C3-C8)cycloalkyl, , 4- to 7- membered heterocycloalkyl, (C1-C6)alkoxy, halo, cyano, formyl, carboxy, or alkoxycarbonyl, wherein (C1-C6)alkyl, (C3-C8)cycloalkyl, 4- to 7-membered heterocycloalkyl, and (C1-C6)alkoxy are each optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, and (C1-C6)alkoxy; or two vicinal occurrences of R1taken together with the atoms to which they are attached form a fused 5- to 7-membered cycloalkyl or 5- to 7-membered heterocycloalkyl ring, either of which is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, and (C1-C6)alkoxy; Q is N or CR2c; R2a, R2b, and R2c, are each independently hydrogen, halo, cyano, or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; R3is (C1-C6)alkyl optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; X and Z are independently NR4, C(R5)2, or O; R4and R5are independently for each occurrence hydrogen or (C1-C6)alkyl, wherein (C1- C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; L is (C1-C6)alkylene optionally substituted with one or more substituents independently selected from halo, hydroxy, C1-C6)alkoxy, and cyano; Wa–Wbrepresents: –C(R6)2–C(R7)2–,–O–C(R8)2–, –C(R8)2–O–, –C(R8)2–NR9–, or –N=C(R10) –; and R6, R7, R8, R9and R10are independently for each occurrence hydrogen or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy.

5. A compound of Formula (III):or a pharmaceutically acceptable salt thereof, wherein: A is (C6-C10)aryl, 5- to 10-membered heteroaryl, (C3-C8)cycloalkyl, or 4- to 7-membered heterocycloalkyl; n is 0, 1, 2, 3, 4, or 5; R1is independently for each occurrence (C1-C6)alkyl, (C2-C6)alkynyl, (C2-C6)alkenyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkoxy, (C6-C10)aryl, (C6-C10)aryloxy, (C6-C10)aryl(C1-C6)alkyl, 4- to 7-membered heterocycloalkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl, halo, cyano, amino, formyl, carboxy, or alkoxycarbonyl, wherein (C1-C6)alkyl, (C2-C6)alkynyl, (C2-C6)alkenyl, (C3-C8)cycloalkyl, C3- C8)cycloalkoxy, (C6-C10)aryl, (C6-C10)aryloxy, (C6-C10)aryl(C1-C6)alkyl, (C1-C6)alkoxy, (C1- C6)alkoxy(C1-C6)alkyl, and 4- to 7-membered heterocycloalkyl are each optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, 4- to 7-membered heterocycloalkyl, 5- to 6- membered heteroaryl, (C1-C6)alkoxy, (C1-C6)haloalkoxy, (C1-C6)fluoroalkoxy, 5- to 6-membered heteroaryloxy, ortwo vicinal occurrences of R1taken together with the atoms to which they are attached form a fused 5- to 7-membered cycloalkyl, 5- to 7-membered heterocycloalkyl ring, 5- to 6- membered heteroaryl ring or phenyl ring, any of which is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C1-C6)haloalkyl (C3-C8)cycloalkyl, and (C1-C6)alkoxy; Q is N or CR2c; R2a, R2b, and R2c, are each independently hydrogen, halo, cyano, (C1-C6)alkyl, or (C3- C8)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; R3is (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C6)alkyl), (C6-C10)aryl, (C6- C10)aryl(C1-C6)alkyl), or 4- to 7-membered heterocycloalkyl; each of which is optionally substituted with one or more substituents independently selected from halo, cyano, (C1-C6)alkyl, (C1-C6)haloalkyl, hydroxy, (C1-C6)alkoxy(C1-C6)alkyl, and (C1-C6)alkoxy; X and Z are independently NR4, C(R5)2, or O; R4and R5independently for each occurrence hydrogen or (C1-C6)alkyl, wherein (C1- C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy, or when Z is NR4, R3and R4taken together with the nitrogen to which they are attached form a 4- to 7-member heterocycloalkyl optionally substituted with one or more (C1-C6)alkyl or halo, or when Z is C(R5)2, R3and one R5taken together with the carbon to which they are attached form a 4, (C3-C8)cycloalkyl optionally substituted with one or more (C1-C6)alkyl or halo; L is (C1-C6)alkylene optionally substituted with one or more substituents independently selected from halo, hydroxy, C1-C6)alkoxy, and cyano; R10is hydrogen, (C1-C6)alkyl,or NH2, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, cyano, hydroxy, (C1-C6)alkoxy(C1-C6)alkyl, and (C1-C6)alkoxy.

6. A compound of Formula (III):or a pharmaceutically acceptable salt thereof, wherein A is (C6-C10)aryl or 5- to 10-membered heteroaryl; n is 0, 1, 2, 3, 4 or 5; R1is independently for each occurrence (C1-C6)alkyl, (C3-C8)cycloalkyl, 4- to 7- membered heterocycloalkyl, (C1-C6)alkoxy, halo, cyano, formyl, carboxy, or alkoxycarbonyl, wherein (C1-C6)alkyl, (C3-C8)cycloalkyl, 4- to 7-membered heterocycloalkyl, and (C1-C6)alkoxy are each optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, and (C1-C6)alkoxy; or two vicinal occurrences of R1taken together with the atoms to which they are attached form a fused 5- to 7-membered cycloalkyl or 5- to 7-membered heterocycloalkyl ring, either of which is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1-C6)alkyl, (C3-C8)cycloalkyl, and (C1-C6)alkoxy; Q is N or CR2c; R2a, R2b, and R2c, are each independently hydrogen, halo, cyano, (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; R3is (C1-C6)alkyl optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; X and Z are independently NR4, C(R5)2, or O; R4and R5are independently for each occurrence hydrogen or (C1-C6)alkyl, wherein (C1- C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy; L is (C1-C6)alkylene optionally substituted with one or more substituents independently selected from halo, hydroxy, C1-C6)alkoxy, and cyano; andR10is hydrogen or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy.

7. The compound of any one of claims 1 to 6, wherein A is phenyl.

8. The compound of any one of claims 1 to 6, wherein A is a 5- to 7-membered heteroaryl comprising 1 or 2 nitrogen atoms.

9. The compound of claim 8, wherein A is pyridyl or diazolyl. thiazolyl, pyrazinyl, pyrimidinyl, 10. The compound of claim 9, wherein A is pyridyl or diazolyl.

11. The compound of any one of claims 1 to 6, wherein A is isoquinolinyl or indazolyl.

12. The compound of any one of calims 1 to 6, wherein A is cyclopentyl, cyclohexyl, or tetrahydropyranyl.

13. The compound of any one of claims 1 to 12, wherein R1is independently for each occurrence (C1-C6)alkyl, (C1-C6)alkoxy, fluoro, chloro, or cyano, wherein (C1-C6)alkyl and (C1- C6)alkoxy are optionally substituted with one or more substituents independently selected from fluoro and hydroxyl.

14. The compound of any one of claims 1 to 12, wherein at least one R1is fluoro, chloro, or cyano.

15. The compound of any one of claims 1 to 14, wherein at least one R1is (C1-C6)alkyl optionally substituted with one or more substituents independently selected from hydroxyl and fluoro, 16. The compound claim 15, wherein at least one R1is 2,2,2-trifluoroethyl-1-hydroxyethyl.

17. The compound claim 15, wherein at least one R1wherein at least one R1is difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluropropyl, or 4,4,4-trifluorobutyl.

18. The compound of any one of claims 1 to 14, wherein at least one R1is (C1-C6)alkoxy optionally substituted with at least one fluoro.

19. The compound of claim 18, wherein at least one R1is difluoromethoxy or trifluoromethoxy.

20. The compound of claim 18, wherein at least one R1is methoxy or isopropoxy.

21. The compound of any one of claims 1 to 14, wherein at least one R1is methyl optionally substituted with hydroxy or one or more fluoro.

22. The compound of any one of claims 1 to 14, wherein at least R1is (C1-C6)alkyl substituted with an amido having the structure:.

23. The compound of any one of claims 1 to 14, wherein at least one R1is (C3-C8)cycloalkyl.

24. The compound of claim 23, wherein the (C3-C8)cycloalkyl is cyclopropyl or cyclobutyl.

25. The compound of any one of claims 1 to 14, wherein at least R1is (C3-C8)cycloalkoxy.

26. The compound of claim 25, wherein the (C3-C8)cycloalkoxy is cyclopentyloxy or cyclohexyloxy.

27. The compound of any one of claims 1 to 14, wherein R1is (C2-C6)alkynyl optionally substituted with hydroxy.

28. The compound of any one of claims 1 to 12, wherein two vicinal occurrences of R1taken together with the atoms to which they are attached form a fused 5- to 7-membered cycloalkyl or 5- to 7-membered heterocycloalkyl ring, either of which is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, amido, sulfonamido, (C1- C6)alkyl, (C3-C8)cycloalkyl, and (C1-C6)alkoxy.

29. The compound of claim 28, wherein A is phenyl comprising two vicinal occurrences of R1, wherein the two vicinal occurrences of R1, taken together with the atoms to which they are attached, form a fused 5- to 7-membered cycloalkyl or 5- to 7-membered heterocycloalkyl ring.

30. The compound of any one of claims 1 to 27, wherein n is 2.

31. The compound of any one of claims 1 to 27, wherein n is 1.

32. The compound of any one of claims 1 to 12, wherein n is 0.

33. The compound of any one of claims 1 to 32, wherein Q is CR2c.

34. The compound of any one of claims 1 to 32, wherein Q is N.

35. The compound of any one of claims 1 to 33, wherein R2a, R2b, and R2care each hydrogen.

36. The compound of any one of claims 1 to 33, wherein at least one of R2a, R2b, and R2cis fluoro, chloro, or cyano.

37. The compound of any one of claims 1 to 36, wherein R3is (C1-C6)alkyl optionally substituted with hydroxy.

38. The compound of claim 37, wherein R3is t-butyl.

39. The compound of any one of claims 1 to 36, wherein R3is (C3-C8)cycloalkyl optionally substituted with one or more (C1-C6)alkyl, (C1-C6)fluoroalkyl, fluoro, or (C1-C6)alkoxy(C1-C6)alkyl.

40. The compound of claim 39, wherein the (C3-C8)cycloalkyl is cyclobutyl, cyclopentyl, cylohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl,bicycle[2.1.1]hexanyl, or bicyclo[3.1.0]hexanyl.

41. The compound of claim 40 or 41, wherein the (C3-C8)cycloalkyl is optionally substituted with one or more substituents selected from fluoro, trifluoromethyl, methoxymethyl, methyl, and hydroxyl.

42. The compound of any one of claims 1 to 36, wherein R3is 4- to 7-membered heterocycloalkyl optionally substituted with one or more substituents selected from (C1-C6)alkyl, (C1-C6)fluoroalkyl, or fluoro.

43. The compound of claim 42, wherein the 4- to 7-membered heterocycloalkyl is etrahydropyranyl or oxetanyl.

44. The compound of any one of claims 1 to 36, wherein Z is NR4, R3and R4taken together with the nitrogen to which they are attached form a 4- to 7-member heterocycloalkyl optionally substituted with one or more (C1-C6)alkyl or halo.

45. The compound of claim 44, wherein the 4- to 7 membered heterocycloalkyl is azetidine or pyrrolidine, 46. The compound of any one of claims 1 to 45, wherein X is NR4or O.

47. The compound of any one of claims 1 to 45 wherein X is NH.

48. The compound of any one of claims 1 to 43 and 46 to 47, wherein Z is NR4, or O.

49. The compound of any one of claims 1 to 43 and 46 to 47, wherein Z is NH.

50. The compound of any one of claims 1 to 49, wherein one and only one of X and Z is CH2.

51. The compound of any one of claims 1 to 43 and 46 to 47, wherein X and Z are each NH.

52. The compound of any one of claims 1 to 51, wherein L is unsubstituted (C1-C6)alkylene.

53. The compound of any one of claims 1 to 51, wherein L is (C1-C6)alkylene substituted with hydroxy.

54. The compound of any one of claims 1 to 51, wherein L is (C1-C6)alkylene substituted with 1 to 3 halo atoms.

55. The compound of any one of claims 1 to 51, wherein L is –CH2–, –-CH(CH3)–, –CH(CH2CH3)–, or –CH(CH2OH)–.

56. The compound of any one of claims 2 to 55, wherein Wa–Wbrepresents: –C(R6)2–C(R7)2–.

57. The compound of claim 56, wherein at least one R6is (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, and (C1-C6)alkoxy.

58. The compound of claim 56 or 57, wherein at least one R7is (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more substituents independently selected from halo, hydroxy, (C1-C6)alkoxy and cyano.

59. The compound of claim 56, wherein each R6and each R7is hydrogen.

60. The compound of any one of claims 2 to 55, wherein: Wa–Wbrepresents: –O–C(R8)2–.

61. The compound of claim 60, wherein each R8is hydrogen.

62. The compound of claim 60, wherein one R8is (C1-C6)alkyl; and one R8is hydrogen.

63. The compound of claim 62, wherein one R8is methyl.

64. The compound of any one of claims 2 to 55, wherein: Wa–Wbrepresents: –C(R8)2–O–.

65. The compound of claim 64, wherein each R8is hydrogen.

66. The compound of any one of claims 2 to 30, wherein: Wa–Wbrepresents: –C(R8)2–NR9–.

67. The compound of claim 66, wherein each R8is hydrogen.

68. The compound of claim 66 or 67, wherein R9is (C1-C6)alkyl.

69. The compound of claim 68, wherein R9is methyl.

70. The compound of any one of claims 2 to 55, wherein: Wa–Wbrepresents: –N=C(R10) –.

71. The compound of claim 70, wherein R10is hydrogen.

72. The compound of claim 70, wherein R10is (C1-C6)alkyl.

73. The compound of claim 70, wherein R10is methyl.

74. A compound selected from the following table:or a pharmaceutically acceptable salt thereof.

75. A compound selected from the following table:or a pharmaceutically acceptable salt thereof.

76. A pharmaceutical composition, comprising a compound of any one of claims 1 to 75; and at least one pharmaceutically acceptable excipient.

77. A method of inhibiting a thyroid stimulating hormone receptor, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of any one of claims 1 to 75.

78. A method of treating hyperthyroidism, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of any one of claims 1 to 75.

79. The method of claim 78, wherein the subject has Graves' disease.

80. The method of claim 79 wherein the subject has Graves' ophthalmopathy.

81. The method of claim 79 or 80, wherein the subject has Graves' dermopathy.

82. The method of claim 78, wherein the subject has thyroid cancer.

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