Substitute quinoxalines

Abstract

This specification describes substituted quinoxalines, methods for producing the same, and uses thereof.

Description

[Technical Field]

[0001] (Cross-reference of related applications) This application claims priority derived from U.S. Provisional Patent Application No. 63 / 501,970 filed 12 May 2023, U.S. Provisional Patent Application No. 63 / 522,325 filed 21 June 2023, and U.S. Provisional Patent Application No. 63 / 578,523 filed 24 August 2023, the disclosures of each application being incorporated in their entirety by attribution.

[0002] (Field of invention) This disclosure is directed to substituted quinoxalines, more specifically to inhibitors of phosphoinositide 3-kinase (PI3K), and thus to compounds useful for treating diseases or disorders related to the modulation of PI3K. This disclosure is directed to compounds and compositions that inhibit PI3K, to methods for treating diseases or disorders related to PI3K (e.g., CLOVES syndrome (congenital lipomatous hypergrowth, vascular malformations, epidermal nevi, scoliosis / skeletal and spinal syndrome), PIK3CA-associated hypergrowth syndrome (PROS), breast cancer, brain cancer, prostate cancer, endometrial cancer, gastric cancer, leukemia, lymphoma, sarcoma, colorectal cancer, lung cancer, ovarian cancer, skin cancer, or head and neck cancer), and to methods for using PI3K inhibitors in combination with therapies for one or more further disorders or cancers. [Background technology]

[0003] Cellular activity can be controlled by external signals that stimulate or inhibit intracellular events. The process by which stimuli or inhibitory signals are transmitted within and within cells, thereby inducing intracellular responses, is called signal transduction. Over the past few decades, signal transduction cascades have been elucidated and revealed to play a central role in various biological responses. It has been found that defects in various components of signal transduction pathways can explain a vast number of diseases, including numerous forms of cancer, inflammatory disorders, metabolic disorders, and vascular and neurological diseases.

[0004] Kinases represent a series of important signaling molecules. Kinases can generally be classified into protein kinases and lipid kinases, with certain kinases exhibiting bispecificity. Protein kinases are enzymes that phosphorylate other proteins and / or phosphorylate themselves (autophosphorylation). Protein kinases can generally be classified into three main groups based on their substrate utilization: tyrosine kinases (e.g., erb2, PDGF receptor, EGF receptor, VEGF receptor, src, abl), which primarily phosphorylate good substrates on tyrosine residues; serine / threonine kinases (e.g., mTORC1, mTORC2, ATM, ATR, DNA-PK, Akt), which primarily phosphorylate substrates on serine and / or threonine residues; and bispecific kinases, which phosphorylate substrates on tyrosine, serine, and / or threonine residues.

[0005] Lipid kinases are enzymes that catalyze the phosphorylation of lipids within cells. These enzymes, as well as the resulting phosphorylated lipids and lipid-inducing biologically active organic molecules, play a role in many different physiological processes, including cell proliferation, migration, adhesion, and differentiation. Certain groups of lipid kinases include membrane lipid kinases, i.e., kinases that catalyze the phosphorylation of lipids contained in or associated with the cell membrane. Examples of such enzymes include phosphoinositide kinases (PI3-kinase, PI4-kinase, etc.), diacylglycerol kinases, and sphingosine kinases.

[0006] The phosphoinositide 3-kinase (PI3K) signaling pathway is one of the most highly mutated systems in human cancer. PI3K signaling is involved in many other conditions, including allergic contact dermatitis, rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, chronic obstructive pulmonary disease, psoriasis, multiple sclerosis, asthma, diabetes complications, and cardiovascular inflammatory complications such as acute coronary syndrome.

[0007] PI3K is a unique and conserved family of intracellular lipid kinases that phosphorylate the 3'-OH group on phosphatidylinositol or phosphoinositides. The PI3K family comprises 15 kinases with differing substrate specificity, expression patterns, and regulatory modes. Class I PI3Ks (pi10a, pi10b, pi106, and pi10g) are typically activated by tyrosine kinases or G protein-coupled receptors to produce PIP3, which engages with downstream effectors such as Akt / PDKl, mTOR, Tec family kinases, and Rho family GTPases. Class II and III PI3Ks play crucial roles in intracellular transport through the synthesis of PI(3)P and PI(3,4)P2.

[0008] PI3K isoforms are involved in various human cancers and disorders, for example. Mutations in the genes encoding PI3K isoforms, or mutations resulting in upregulation of PI3K isoforms, are thought to occur in many human cancers. Mutations in the genes encoding PI3K isoforms are point mutations clustered in several hotspots within the helical and kinase domains. Due to the high rate of PI3K mutations, targeting this pathway may offer a valuable therapeutic opportunity.

[0009] Genetic alterations in the PI3K signaling pathway are thought to be involved in a group of cancers, including endometrial cancer, breast cancer, esophageal squamous cell carcinoma, cervical squamous cell carcinoma, cervical adenocarcinoma, colorectal adenocarcinoma, bladder and urinary tract carcinoma, glioblastoma, ovarian cancer, non-small cell lung cancer, esophageal and gastric cancer, nerve sheath tumors, head and neck squamous cell carcinoma, melanoma, esophageal and gastric adenocarcinoma, soft tissue sarcoma, prostate cancer, fibrous laminae carcinoma, hepatocellular carcinoma, diffuse glioma, colorectal cancer, pancreatic cancer, cholangiocarcinoma, B-cell lymphoma, mesothelioma, adrenocortical carcinoma, renal non-clear cell carcinoma, renal clear cell carcinoma, germ cell carcinoma, thymic tumor, pheochromocytoma, other neuroepithelial tumors, thyroid cancer, leukemia, and encapsulated glioma.

[0010] The alpha (α) isoform of PI3K has been shown to be involved in various human cancers, for example. Angiogenesis has been shown to selectively require the alpha (α) isoform of PI3K to control endothelial cell migration. Mutations in the gene encoding PI3Kα, or mutations resulting in PI3Kα upregulation, are thought to occur in many human cancers, including lung cancer, gastric cancer, endometrial cancer, ovarian cancer, bladder cancer, breast cancer, colon cancer, brain cancer, prostate cancer, and skin cancer. Mutations in the gene encoding PI3Kα are point mutations clustered within multiple hotspots in the helical and kinase domains, such as E542K, E545K, and H1047R. Many of these mutations have been shown to be oncogenic gain-of-function mutations. Due to the high rate of PI3Kα mutations, targeting this pathway may offer a valuable therapeutic opportunity. While other PI3K isoforms, such as PI3Kδ or PI3Kγ, are primarily expressed in hematopoietic cells, PI3Kα is constitutively expressed together with PI3Kβ.

[0011] Since the central role of PI3Kα is to regulate glucose homeostasis in the body, PI3K inhibition in patients often leads to hyperglycemia and / or hyperinsulinemia. Circulating insulin, at high levels, may have mitotic and / or anti-apoptotic effects on cancer cells, thus potentially counteracting the antiproliferative effects of PI3K inhibitors.

[0012] In setting up cancers with mutated PI3Kα, one way to overcome the compensatory insulin and / or glucose production problems associated with systemic PI3Kα inhibition would be to develop inhibitors that are more selective to mutant PI3Kα than to wild-type PI3Kα. This would provide a larger window for drug doses to selectively inhibit the pathological signaling of mutant PI3Kα in cancer cells without affecting wild-type PI3Kα in host tissues that control systemic metabolic activity, thus limiting toxicity and enabling more complete inhibition of the drug target at higher doses.

[0013] Existing PI3Kα inhibitors are almost equivalent against wild-type and mutant PI3Kα. Since the position of the PI3Kα mutation is far from the active site, it has been difficult to achieve mutant-selective inhibitors. Inhibitors that target a second peripheral binding pocket near known mutations (e.g., H1047R) may provide a path to selective PI3Kα inhibition. Thus, targeting the mutated peripheral binding pocket of PI3Kα may potentially provide a valuable therapeutic target for drug development in sequence. Kinases, such as lipid kinases themselves like PI3Kα, are major targets for drug development. SUMMARY OF THE INVENTION

[0014] In one aspect, the present disclosure provides a compound of formula (I):

Chemical formula

[0015] In another aspect, the present disclosure provides a pharmaceutical composition comprising a compound or salt described separately herein, together with a pharmaceutically acceptable carrier, excipient or diluent. In another aspect, the present disclosure provides a method of treating a disease or disorder associated with the regulation of phosphoinositide 3-kinase (PI3K), the method comprising administering to a patient in need thereof any compound described separately herein, or a pharmaceutical composition described separately herein, in a therapeutically effective amount.

[0016] In another aspect, the present disclosure provides a method of inhibiting phosphoinositide 3-kinase (PI3K), the method comprising administering to a patient in need thereof a compound described separately herein, or a pharmaceutical composition described separately herein, in a therapeutically effective amount.

[0017] In another aspect, the present disclosure provides a method of treating cancer or a disorder, the method comprising administering to a patient in need thereof a compound described separately herein, or a pharmaceutical composition described separately herein, in a therapeutically effective amount.

[0018] The compounds disclosed herein selectively bind to H1047R mutant PI3Kα and do not bind to wild-type PI3Kα. In another aspect, the present disclosure provides an intermediate described herein, which is suitable for use in a method of manufacturing a compound described herein. Other aspects and embodiments of the present disclosure will be apparent in view of the forms for carrying out the invention provided herein.

Forms for Carrying Out the Invention

[0019] The present invention relates to inhibitors of PI3Kα. In particular, the present invention relates to compounds that inhibit PI3Kα activity, to pharmaceutical compositions comprising such compounds in a therapeutically effective amount, and to methods of using them.

[0020] definition Unless otherwise specified, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which the present invention pertains. All patents, patent applications, and publications referenced herein are incorporated herein to the extent consistent with this disclosure by indicating their sources. Terms and scopes have their generally defined meanings unless otherwise specified.

[0021] For brevity, chemical groups are defined and referred to throughout primarily as monovalent chemical groups (e.g., alkyl, aryl, etc.). However, such terms can also be used to represent corresponding polyvalent groups under appropriate structural circumstances that are obvious to those skilled in the art. For example, while “alkyl” generally refers to a monovalent group (e.g., CH3-CH2-), under certain circumstances a divalent linking group can be called “alkyl,” in which case those skilled in the art will recognize that alkyl is a divalent group (e.g., -CH2-CH2-) and is synonymous with the term “alkylene.” (Similarly, when “aryl” is used in situations where a divalent group is required, those skilled in the art will recognize that the term “aryl” refers to the corresponding divalent group, arylene.) It is recognized that all atoms have their normal valence number for forming bonds (i.e., 4 for carbon, 3 for N, 2 for O, and 2, 4, or 6 for S, depending on the oxidation state of its S).

[0022] The term "amino" refers to -NH2. The term "acetyl" refers to -C(O)CH3. As used herein, the term "acyl" means an alkylcarbonyl or arylcarbonyl substituent, where the alkyl and aryl portions are as defined herein.

[0023] As used herein, the term "alkyl" refers to saturated linear and branched aliphatic groups having 1 to 12 carbon atoms. Thus, "alkyl" refers to C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 and C 12 The group is included. The alkyl group may be branched or unbranched. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, and hexyl.

[0024] As used herein, the term "alkenyl" means an unsaturated, linear or branched aliphatic group having 2 to 12 carbon atoms and containing one or more carbon-carbon double bonds. Thus, "alkenyl" refers to C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 and C 12 It includes the group. Examples of alkenyl groups include, but are not limited to, ethenyl, propenyl, butenyl, pentenyl, and hexenyl.

[0025] As used herein, the term "alkynyl" means an unsaturated, linear or branched aliphatic group having 2 to 12 carbon atoms and containing one or more carbon-carbon triple bonds. Thus, "alkynyl" refers to C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 and C 12 It includes the group. Examples of alkynyl groups include, but are not limited to, ethynyl, propynyl, butynyl, pentynyl, and hexynyl.

[0026] The "alkylene," "alkenylene," or "alkynylene" group is an alkyl, alkenyl, or alkynyl group as defined above, located between two other chemical groups and used to link them together. Examples of alkylene groups include, but are not limited to, methylene, ethylene, propylene, and butylene. Representative alkenylene groups include, but are not limited to, ethenylene, propenylene, and butenylene. Representative alkynylene groups include, but are not limited to, etynylene, propynylene, and butynylene. The term "alkoxy" refers to -O (C1-C6 alkyl).

[0027] The phrase "amino, mono, or di(C1-C3) alkylaminocarbonyl" refers to the carbamoyl group, i.e., formula: [ka] [In the formula, R 14 and R 15 [These independently represent hydrogen and C1-C3 alkyl.] This refers to the base indicated by [the symbol].

[0028] As used herein, the term "cycloalkyl" refers to saturated and partially unsaturated cyclic hydrocarbon groups having 3 to 12 carbon atoms. Thus, "cycloalkyl" refers to C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 and C 12 It includes the cyclic hydrocarbon group. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, and cyclooctyl. The term "cycloalkyl" also includes crosslinking ring systems such as bicyclo[1.1.1]pentan-2-yl, bicyclo[1.1.1]pentan-1-yl, and bicyclo[2.2.2]octane-2-yl.

[0029] The term "C3-C6 cycloalkyloxy" refers to a group represented by the formula: -O(C3-C6 cycloalkyl). The term "heteroalkyl" refers to an alkyl group as defined above, where one or more carbon atoms in the chain are independently replaced by O, S, or NRx, where Rx is hydrogen or C1-C3 alkyl. Examples of heteroalkyl groups include methoxymethyl, methoxyethyl, and methoxypropyl.

[0030] An "aryl" group is a C6-C14 aromatic moiety containing one or three aromatic rings. Thus, "aryl" includes C6, C 10 , C 13 , and C 14 cyclic hydrocarbon groups. Representative aryl groups are C6-C 10 aryl groups. Specific aryl groups include, but are not limited to, phenyl, naphthyl, anthracenyl, and fluorenyl. An "aryl" group also includes fused polycyclic (e.g., bicyclic) ring systems where one or more of the fused rings are non-aromatic: provided that at least one ring is an aromatic ring such as indenyl.

[0031] An "aralkyl" or "arylalkyl" group contains an aryl group covalently attached to an alkyl group, where the moiety is attached to another group through the alkyl portion. Representative aralkyl groups include, but are not limited to, benzyl, phenethyl, and naphthylmethyl, and are -(C1-C6)alkyl(C6-C 10 )aryl. For example, arC1-C3alkyl is an aryl group covalently attached to a C1-C3 alkyl.

[0032] As used herein, the term “condensed” refers to a ring, for example, a bicyclic, tricyclic, or other ring system that shares two or more atoms, when used to define a bicyclic condensed ring system. Examples of such condensed ring systems include (1S,4R)-2-azabicyclo[2.2.1]heptane; 2-azabicyclo[2.2.2]octane, 2,5-diazabicyclo[2.2.2]octane; 2-oxa-5-azabicyclo[2.2.2]octane; isoindoline; 1,2,3,4-tetrahydro-2,6-naphthyridine, 1,2,3,4-tetrahydroisoquinoline; 1,2,3,4-tetrahydro-1,4-(epuiminomethano)naphthalene; and 3-azabicyclo[3.1.0]hexane.

[0033] A "heterocyclyl," "heterocyclic," or "heterocycloalkyl" group is a monocyclic or bicyclic (condensed or spirocyclic) ring structure having 3 to 12 atoms (3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 atoms), for example, 4 to 8 atoms; where one or more ring atoms are independently -C(O)-, N, NR 4The group consists of O, or S, with the remaining ring atoms being quaternary or carbonyl carbons. Examples of heterocyclic groups include, but are not limited to, epoxy, oxylanil, oxetanil, azetidinil, azilidinil, tetrahydrofuranil, tetrahydropyranil, tetrahydrothiophenyl, pyrrolidinil, piperidinil, piperazinil, imidazolidinil, thiazolidinil, thiatanil, dithianil, trithianil, azathianil, oxathianil, dioxolanil, oxazolidinil, oxazolidinyl, decahydroquinolinil, piperidonil, 4-piperidonil, thiomorpholinil, dimethylmorpholinil, and morpholinil. Examples of heterocyclic groups that are spirocyclic are 6-azaspiro[2.5]octan-6-yl, 5-azaspiro[2.4]heptane-5-yl, 6-azaspiro[3.4]octan-6-yl, 5-oxa-7-azaspiro[3.4]octan-7-yl, 5,5-dimethyl-4-oxa-7-azaspiro[2.5]octan-7-yl, 2-oxa-6-azaspiro[3.3]heptane-6-yl, 1-oxa-6-azaspiro[3.4]octan-6-yl, and 7,7-dimethyl-5-azaspiro[2.5]octan-5-yl. Compounds having adjacent ring atoms O and / or S are specifically excluded from the scope of this term. A heterocyclic group may be bonded to a parent group (i.e., a bonding site) via any ring atom, including one heteroatom or one carbon atom of the heterocyclic ring group. If chemically necessary, the heterocyclic ring may be bonded to one or more other groups, for example, if they function as bridging groups. Thus, the term “heterocyclyl” encompasses groups such as azabicyclo[2.1.1]hexane-2-yl, azabicyclo[2.2.1]heptan-7-yl, 6-oxa-3-azabicyclo[3.1.1]heptan-3-yl, diazabicyclo[3.1.1]heptan-6-yl, and hexahydro-3,5-methanocyclopenta[b]pyrrole-1(2H)-yl. The term "heterocyclyl" also encompasses fused polycyclic (e.g., bicyclic) ring systems in which one or more fused rings are aromatic or non-aromatic, provided that at least one ring is non-aromatic and contains an N, O, or S ring atom.Examples of such condensed polycyclic ring systems include indolinyl, indolin-2-yl, 2,3-dihydrobenzofuran-2-yl, and 2,3,4,5-tetrahydrobenzo[d]oxazole-2-yl. All of these examples are nine-membered heterocyclyls.

[0034] As used herein, the term “heteroaryl” means a group having 5 to 14 ring atoms, preferably 5, 6, 10, 13, or 14 ring atoms; sharing 6, 10, or 14 π electrons in a cyclic array; and having 1 to 3 heteroatoms, each independently being N, O, or S, in addition to the carbon atoms. “Heteroaryl” also encompasses fused polycyclic (e.g., bicyclic) ring systems in which one or more fused rings are non-aromatic: provided that at least one ring is aromatic and at least one ring contains an N, O, or S ring atom. A heteroaryl group may be bonded to a parent group (i.e., a bonding site) via any ring atom, including one heteroatom or one carbon atom of the heteroaryl ring group. If chemically required, a heteroaryl may be bonded to one or more other groups, for example, to function as a bridging group.

[0035] Examples of heteroaryl groups include acridinyl, azotinyl, benzimidazolyl, benzofuranil, benzo[d]oxazole-2(3H)-one, 2H-benzo[b][1,4]oxazine-3(4H)-one, benzothiofuranil, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolinyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanil, chromenyl, sinnolinyl, furanil, and furanil. Zanil, imidazolinil, imidazolyl, 1H-indazolyl, indolenil, indolinyl, indolidinil, indolyl, 3H-indolyl, isobenzofuranil, isochromanil, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinil, isothiazolyl, isoxazolyl, naphthilidinil, octahydroisoquinolinil, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinil, oxazoli Oxazolidinil, pyrimidinil, phenanthrolinil, phenanthrolinil, phenazinil, phenothiazinil, phenoxathiinil, phenoxadinil, phthalazinil, piperonil, phteridinil, prinil, pyranil, pyrazinil, pyrazolidinil, pyrazolinil, pyrazolyl, pyridazinil, pyridoxazole, pyridoimidazole, pyridothiazole, pyridinil, pyridyl, pyrimidinil, pyrrolinil, 2H-pyrrolyl, pyrrrolyl, quinazolinil, quinolinil, 4H-quinolidinil, quinoxalinil, quinuclidyl Examples include nyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienoxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, and xanthenyl.

[0036] The "arylene," "heteroarylene," or "heterocyclylene" groups are, respectively, divalent aryl, heteroaryl, or heterocyclyl groups as defined above, located between two other chemical groups and serving to link them together. As used herein, when a portion (e.g., cycloalkyl, aryl, heteroaryl, heterocyclyl, urea, etc.) is described as "may be optionally substituted" without specifying the substituents, it means that the group may optionally have multiple non-hydrogen substituents, for example, 1 to 5, 1 to 4, 1 to 3, or 1 or 2 non-hydrogen substituents.

[0037] As used herein, the terms "halogen" or "halo" refer to chlorine, bromine, fluorine, or iodine. The term "haloalkyl" refers to an alkyl chain in which one or more hydrogen atoms are replaced by halogens. Typical haloalkyls include trifluoromethyl, difluoromethyl, fluorochloromethyl, chloromethyl, and fluoromethyl. The term "hydroxyalkyl" refers to -alkylene-OH.

[0038] Each individual atom present in formula (I) and in compounds within the range of formula (I) may exist in any naturally occurring isotopic form, but the most abundant isotope is preferred. Thus, as an example, each individual hydrogen atom present in formula (I) or in the formulas described below, 1 H, 2 H (deuterium; D) or 3 H (tritium; T) atom, preferably 1 It may also exist as H. Similarly, as an example, each individual carbon atom present in formula (I) or the formula described below, 12 C, 13 C or 14 C atom, preferably a C atom. 12 It may exist as C.

[0039] The specific deuterium compounds of this disclosure are R 5A A compound in which one or more hydrogen atoms are replaced by deuterium. A typical deuterium R 5A The groups are pyrrolidine-1-yl-d8, morpholino-d8, (piperazine-1-yl-2,2,3,3,5,5,6,6-d8), and piperidine-1-yl-d 10 That is the case. As used herein, the “effective amount” of a compound is an amount sufficient to negatively modulate or inhibit the activity of PI3Kα.

[0040] As used herein, a “therapeutably effective amount” of a compound is an amount sufficient to improve or alleviate symptoms in any way, to halt or reverse the progression of a disease, or to negatively modulate or inhibit the activity of PI3Kα. Such an amount may be administered as a single dose or according to a dosage regimen in which it is effective. As used herein, “treatment” means any method by which a patient’s medical condition, disorder, or sign or symptom of disease is improved or otherwise beneficially altered. As used herein, “improvement of signs of a particular disorder by administration of a particular compound or pharmaceutical composition” means any reduction, whether permanent or temporary, sustained or transient, that is caused by or associated with the administration of the composition.

[0041] compound In one embodiment, this disclosure relates to formula (I): [ka] [In formula: R 1 is H, C1-C3 alkyl, or C3-C6 cycloalkyl; R 2 R is a phenyl or 5-6 membered heteroaryl group, where phenyl and heteroaryl each have 1-5 R 12 It may be replaced as desired; R 12 Each of these is independently a C1-C4 alkyl, -OR A , -C(O)OR A (C1-C3 alkyl)-OR A ,-C(O)N(R A )2, cyano, tetrazolyl, or halogen; R A Each of these is independently H, C1-C6 alkyl, C3-C6 cycloalkyl, cycloalkyl, or 2-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-6-yl; R 3 These are C1-C3 alkyl, C3-C6 cycloalkyl, C1-C3 alkenyl, C2-C3 alkynyl, or C5-C6 cycloalkenyl molecules, which may be optionally substituted, polysubstituted, or oversubstituted with fluoropolymers; R 4 is H, halogen, C1-C3 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, C1-C3 alkenyl, C2-C3 alkynyl, C5-C6 cycloalkenyl, or cyano, where C1-C3 alkyl and C3-C6 cycloalkyl may each be optionally substituted with 1 to 5 halo groups; R 6 and R 6A This independently represents H or C1-C6 alkyl; R 5 is hydrogen, -OR 20 , -SR 20, C1-C6 alkyl, halogen, hydroxy, cyano, halo-C1-C3 alkyl, hydroxy-C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkoxy(C1-C6) alkyl, cyano, amino, mono or di(C1-C3) alkylamino, C3-C6 cycloalkyl, C3-C6 cycloalkyl(C1-C3 alkyl), 3- to 8-membered heterocyclil, phenyl, or 5- to 6-membered heteroaryl, where alkyl, alkenyl, cycloalkyl, phenyl, 3- to 8-membered heterocyclil, and heteroaryl may each be independently and optionally substituted with 1 to 3 halogens, hydroxy, C1-C3 alkyl, C1-C3 alkoxy, halo-C1-C3 alkyl, hydroxy-C1-C6 alkyl, oxo, cyano, amino, mono or di(C1-C3) alkylamino. Here, R 20 is an aryl, aryl(C1-C6)alkyl, 5-7 membered heteroaryl, or 5-7 membered heteroaryl(C1-C6)alkyl, where the aryl and heteroaryl may each be independently and optionally substituted with 1-4 C1-C6 alkyl, halogen, hydroxy, cyano, haloC1-C3 alkyl, hydroxyC1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkoxy(C1-C6)alkyl, cyano, amino, or mono or di(C1-C3)alkylamino; R 5A , NR 7 R 8 , represents a C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl(C1-C3 alkyl), phenyl, or a 5-6 membered heteroaryl, where C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl(C1-C3 alkyl), phenyl, and heteroaryl may each be independently and optionally substituted with 1-3 halogens, halo(C1-C3 alkyl), hydroxy, oxo, C1-C3 alkyl, C1-C3 alkoxy, C1-C6 alkanoyl, cyano, amino, or mono or di(C1-C3) alkylamino; R 7 represents H or C1-C3 alkyl; R8 represents H, C1-C6 alkyl, C2-C6 alkenyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl(C1-C3 alkyl), 3- to 8-membered heterocyclyl, 3- to 8-membered heterocyclyl(C1-C6)alkyl, phenyl(C1-C6)alkyl, or 5- to 6-membered heteroaryl(C1-C6)alkyl, where C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl(C1-C3 alkyl), phenyl, heteroaryl, and 3- to 8-membered heterocyclyl are each independently substituted with 1 to 3 halogen, halo(C1-C3 alkyl), hydroxy, oxo, C1-C3 alkyl, C1-C3 alkoxy, cyano, amino, mono- or di(C1-C3)alkylamino, amino- or mono- or di(C1-C3)alkylaminocarbonyl, -SO2R 16 , -SO2(NR 16 ),2, or -NR 17 SO2R 16 and may be independently substituted as desired, where each R 16 is independently C1-C6 alkyl, R 17 is C1-C6 alkyl; or R 7 and R 8 together with the nitrogen to which they are attached form ring Q, where ring Q is a 3- to 8-membered monocyclic heterocyclyl group, where the heterocyclyl group contains 3 to 6 ring members, 1 or 2 of which are optionally nitrogen, oxygen or sulfur atoms and the remainder are carbon, and may be optionally fused to an aromatic or non-aromatic ring, or together with carbon atoms from a monocyclic heterocyclyl group or fused ring system, and additional carbon and heteroatoms, form a spirocyclic ring system having up to 10 ring members in total, where the ring members are carbon and heteroatoms selected from 1 or 2 nitrogen, sulfur and oxygen atoms, where ring Q may be optionally substituted with 1 to 4 R 9 groups in each aromatic or non-aromatic moiety, where R 9Each of these independently comprises (i) a C1-C6 alkyl group which may optionally be substituted with a C1-C3 alkoxy group, (ii) a C1-C6 alkoxy group, (iii) a C3-C6 cycloalkyl group, (iv) a cyano group, (ii) a hydroxy group, (v) an oxo group, (vi) a halogen group, (vii) a halo-C1-C3 alkyl group, (viii) a hydroxy-C1-C6 alkyl group, (ix) an amino group, (x) a mono- or di-(C1-C6 alkyl) amino group (where one alkyl group may optionally be substituted with an oxo group), (xi) C1-C6 alkanoyl, which may optionally be substituted with one or two C1-C3 alkyl, C1-C3 alkoxy, C3-C6 cycloalkyl, cyano, hydroxy, oxo, halogen, halo-C1-C3 alkyl, hydroxy-C1-C3 alkyl, amino, mono or di-(C1-C6 alkyl)amino, C3-C6 cycloalkyl, phenyl, or 5-6 member heteroaryl (where the C1-C3 alkyl and C3-C6 cycloalkyl on the alkanoyl are, respectively) (xii) C3-C6 cycloalkyloxy, (xiii) phenyl, (xiv) phenyl (C1-C3 alkanoyl), (xv) 5-7 member heterocyclyl, or (xvi) 5-6 member heteroaryl (xiv) A compound, where phenyl, a 5-7 membered heterocyclyl, and a 5-6 membered heteroaryl are each optionally substituted with 1-4 C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxy, cyano, oxo, amino, mono or di(C1-C3 alkyl)amino, amino(C1-C3)alkyl, mono or di(C1-C3 alkyl)amino(C1-C3)alkyl, or amino- or mono or di(C1-C3)alkylaminocarbonyl. The present invention provides compounds represented by [formula], as well as pharmaceutically acceptable salts, prodrugs, solvates, hydrates, isomers, deuterated forms, and tautomers thereof.

[0042] In yet another aspect, the present disclosure provides formula (IV):

Chemical formula

[0043] In certain embodiments of formula (I) or formula (IV) described separately herein, R 6 and R 6A This represents hydrogen. In certain embodiments of formula (I) or formula (IV) described separately herein, R 6 and R 6A One of the characters represents hydrogen, and the other represents a C1-C6 alkyl group. In certain embodiments of formula (I) or formula (IV) described separately herein, R 6 and R 6A One of the characters represents hydrogen, and the other represents a C1-C6 alkyl group.

[0044] In certain embodiments of formula (I) or formula (IV) described separately herein, R 6 and R 6A This independently represents a C1-C6 alkyl group. In certain embodiments of formula (I) or formula (IV) described separately herein, R 1 H is H. In certain embodiments of formula (I) or formula (IV) described separately herein, R 1 It is CH3.

[0045] In certain embodiments of formula (I) or formula (IV) described separately herein, R 1 It is either H or CH3. In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 is a phenyl or a 5-7 member heteroaryl, each having 1, 2, or 3 R 12 It is replaced by the base. In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 is a phenyl or a 5-7 member heteroaryl, each having 1, 2, or 3 R 12 Substituted with at least one R 12 The base is -C(O)OR A That is the case.

[0046] In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 is a phenyl or 5-7 member heteroaryl, each having 1, 2, or 3 R 12 Substituted with at least one R 12 The base is -C(O)OR A And here R A The methyl or ethyl ions are H, methyl, or ethyl. In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 R is a phenyl or 5-7 member heteroaryl, each of which has 1, 2, or 3 R12 Substituted with at least one R 12 The base is -C(O)OR A And here R A H is H.

[0047] In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 is a phenyl or 5-7 member heteroaryl, each having 1, 2, or 3 R 12 Substituted with at least one R 12 The base is -C(O)OR A And here R A It is methyl or ethyl. In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 is a phenyl or 5-7 member heteroaryl, each having 1, 2, or 3 R 12 Substituted with at least one R 12 The base is -C(O)OR A And here R A This is 2-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-6-yl. A A suitable compound for producing compounds containing the group is (2S,3S,4S,5R)-3,4,5,6-tetrahydroxytetrahydro-2H-pyran-2-carboxylic acid.

[0048] In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 is a phenyl or 5-7 member heteroaryl, each having 1, 2, or 3 R 12 Substituted with at least one R 12 The base is -C(O)OR A That is the case. In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 is a phenyl or 5-7 member heteroaryl, each having 1, 2, or 3 R 12 Substituted with at least one R 12The group is tetrazolyl, particularly 1H-tetrazole-5-yl.

[0049] In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 These are phenyl, pyridinyl, thienyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, imidazolyl, pyrazolyl, pyrazinyl, pyridadinyl, or pyrimidinyl, each of which has 1 to 5 R 12 It may be replaced as desired. In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 is phenyl or pyridinyl, each of which has 1 to 5 R 12 It may be replaced as desired.

[0050] In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 is phenyl or pyridinyl, each of which has 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A That is the case. In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 is phenyl or pyridinyl, each of which has 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A The methyl or ethyl ions are H, methyl, or ethyl.

[0051] In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 is phenyl or pyridinyl, each of which has 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A H is H. In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 is phenyl or pyridinyl, each of which has 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A It is methyl or ethyl.

[0052] In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 It is phenyl, and it has 1 to 5 R 12 It may be replaced as desired. In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 It is phenyl, and it has 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A That is the case.

[0053] In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 It is phenyl, and it has 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A The methyl or ethyl ions are H, methyl, or ethyl. In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 It is phenyl, and it has 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A H is H.

[0054] In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 It is phenyl, and it has 1 to 5 R 12It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A It is methyl or ethyl. In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 It is pyridinyl, and it has 1 to 5 R 12 It may be replaced as desired.

[0055] In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 It is pyridinyl, and it has 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A That is the case. In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 It is pyridinyl, and it has 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A The methyl or ethyl ions are H, methyl, or ethyl.

[0056] In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 It is pyridinyl, and it has 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A H is H. In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 It is pyridinyl, and it has 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A It is methyl or ethyl.

[0057] In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 It is pyrimidinyl, which has 1 to 5 R 12 It may be replaced as desired. In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 It is pyrimidinyl, which has 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A That is the case. In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 It is pyrimidinyl, which has 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A The methyl or ethyl ions are H, methyl, or ethyl.

[0058] In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 It is pyrimidinyl, which has 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A H is H. In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 It is pyrimidinyl, which has 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A It is methyl or ethyl.

[0059] In certain embodiments of formula (I) or formula (IV) described separately herein, R 3The alkyl group is a C1-C3 alkyl group, where the alkyl group is unsubstituted, substituted with 1 to 5 halo groups, or perfluorinated. In certain embodiments of formula (I) or formula (IV) described separately herein, R 3 The alkyl group is a C1-C3 alkyl group, where the alkyl group is unsubstituted, substituted with 1 to 5 halo groups, or perfluorinated.

[0060] In certain embodiments of formula (I) or formula (IV) described separately herein, R 3 It is a C1-C3 alkyl group. In certain embodiments of formula (I) or formula (IV) described separately herein, R 3 Is it ethyl, or R 3 It is methyl. In certain embodiments of formula (I) described separately herein, R 5 These are hydrogen, C1-C3 alkyl, halo-C1-C3 alkyl, halogen, cyano, C3-C6 cycloalkyl, or C3-C6 cycloalkyl (C1-C3 alkyl).

[0061] In certain embodiments of formula (I) described separately herein, R 5 These are halo-C1-C3 alkyl groups, particularly fluoromethyl, difluoromethyl, or trifluoromethyl groups. In certain embodiments of formula (I) described separately herein, R 5 is a phenyl or a 5-6 membered heteroaryl, where the cycloalkyl, phenyl, and heteroaryl may each be optionally substituted with 1-3 halogens, hydroxy, C1-C3 alkyl, C1-C3 alkoxy, cyano, amino, or mono or di(C1-C3)alkylamino.

[0062] In certain embodiments of formula (I) described separately herein, R 5 These are hydrogen, C1-C3 alkyl, halo-C1-C3 alkyl, halogen, cyano, cyclopropyl, or cyclopropyl(C1-C2 alkyl). In certain embodiments of formula (I) described separately herein, R 5 These are methyl, ethyl, cyclopropyl, or cyano compounds.

[0063] In certain embodiments of formula (I) described separately herein, R 5 It is methyl or cyano. In certain embodiments of formula (I) described separately herein, R 5 These are C1-C3 alkyl, halo-C1-C3 alkyl, halogen, cyano, cyclopropyl, or cyclopropyl(C1-C2 alkyl).

[0064] In certain embodiments of formula (I) described separately herein, R 5 These are hydrogen, halogen, hydroxyl, cyano, or amino. In certain embodiments of formula (I) described separately herein, R 5 The is a cycloalkyl, phenyl, or 5-6 membered heteroaryl, where each cycloalkyl, phenyl, and heteroaryl may optionally be substituted with 1-3 halogens, hydroxy, C1-C2 alkyl, C1-C2 alkoxy, cyano, amino, or mono or di(C1-C2)alkylamino.

[0065] In certain embodiments of formula (I) described separately herein, R 5 is a phenyl or a 5-6 member heteroaryl, where the cycloalkyl, phenyl, and heteroaryl may each be optionally substituted with one or two halogens, hydroxy, C1-C2 alkyl, C1-C2 alkoxy, cyano, amino, or mono or di(C1-C2)alkylamino.

[0066] In certain embodiments of formula (I) described separately herein, R 5This is a heterocyclyl linked to the parent ring system by carbon atoms, and the heterocyclyl may be optionally substituted with 1 to 3 halogens, hydroxyl, C1-C2 alkyl, C1-C2 alkoxy, cyano, amino, or mono or di(C1-C2)alkylamino atoms.

[0067] In certain embodiments of formula (IV) described separately herein, R 5 It is methyl. In certain embodiments of formula (IV) described separately herein, R 5 It is ethyl. In certain embodiments of formula (IV) described separately herein, R 5 It is cyano. In certain embodiments of formula (IV) described separately herein, R 5 It is cyclopropyl.

[0068] In certain embodiments of formula (IV) described separately herein, R 5 It is Bromo. In certain embodiments of formula (IV) described separately herein, R 5 It is fluoro. In certain embodiments of formula (IV) described separately herein, R 5 It is chloroform. In certain embodiments of formula (IV) described separately herein, R 5 It is trifluoromethyl.

[0069] In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 is a phenyl compound that may be substituted as desired. In certain embodiments of formula (I) or formula (IV) described separately herein, R 2 is a pyridinyl which may be substituted as desired. In certain embodiments of formula (I) or formula (IV) described separately herein, R 4 These are hydrogen, fluoro, chloro, methyl, ethyl, trifluoromethyl, or cyano.

[0070] In certain embodiments of formula (I) or formula (IV) described separately herein, R 4 These are hydrogen, fluoro, chloro, methyl, trifluoromethyl, or cyano. In certain embodiments of formula (I) or formula (IV) described separately herein, R 4 These are fluoro, chloro, methyl, cyclopropyl, or cyano compounds. In certain embodiments of formula (I) or formula (IV) described separately herein, R 4 These are fluoro, chloro, methyl, cyclopropyl, trifluoromethyl, or cyano compounds.

[0071] In certain embodiments of formula (I) or formula (IV) described separately herein, R 4 These are fluoromethyl, trifluoromethyl, or cyanomethyl compounds. In certain embodiments of formula (I) or formula (IV) described separately herein, R 4 These are fluoro, methyl, or cyano. In certain embodiments of formula (I) or formula (IV) described separately herein, R 5A This represents C1-C6 alkyl, C3-C6 cycloalkyl, or C3-C6 cycloalkyl (C1-C3 alkyl).

[0072] In certain embodiments of formula (I) or formula (IV) described separately herein, R 5A is NR 7 R 8 It represents. In certain embodiments of formula (I) or formula (IV) described separately herein, R 7 is hydrogen, R 8 This represents hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, or C3-C6 cycloalkyl (C1-C3 alkyl).

[0073] In certain embodiments of formula (I) or formula (IV) described separately herein, R 7 and R8 These, together with the nitrogen atoms to which they bond, form a ring Q, where ring Q is It is a monocyclic heterocyclyl group with 3 to 7 members. The heterocyclyl group has 1 to 4 R 9 The base may be substituted as desired, where R 9 Each of these is independently a C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, cyano, hydroxy, oxo, halogen, halo-C1-C3 alkyl, hydroxy-C1-C6 alkyl, amino, mono or di-(C1-C6 alkyl)amino, or phenyl or phenyl(C1-C3 alkanoyl) (wherein phenyl may optionally be substituted with a C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C1-C3 alkyl)amino).

[0074] In certain embodiments of formula (I) or formula (IV) described separately herein, R 7 and R 8 These, together with the nitrogen atoms to which they bond, form a ring Q, where ring Q is It is a monocyclic heterocyclyl group with 3 to 7 members. The heterocyclyl group is condensed to an aromatic or non-aromatic ring containing 3 to 6 ring members, of which 1 or 2 may optionally be nitrogen atoms and the rest may be carbon atoms, and here The condensed heterocyclyl group has 1 to 4 R groups in the aromatic or non-aromatic moiety. 9 The base may be substituted as desired, where R 9 Each of these is independently a C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, cyano, hydroxy, oxo, halogen, halo-C1-C3 alkyl, hydroxy-C1-C6 alkyl, amino, mono or di-(C1-C6 alkyl)amino, or phenyl or phenyl(C1-C3 alkanoyl) (wherein phenyl may optionally be substituted with a C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C1-C3 alkyl)amino).

[0075] In certain embodiments of formula (I) or formula (IV) described separately herein, R 7 and R 8 These, together with the nitrogen atoms they bind to, form a 3-7 membered monocyclic heterocycline group. The heterocyclyl group, together with the carbon atoms from the monocyclic heterocyclyl group and further carbon, nitrogen, sulfur, or oxygen atoms, forms a spirocyclic ring system with a total of up to 10 ring members, where The spirocyclic ring system has 1 to 4 R 9 The base may be substituted as desired, where R 9 Each of these is independently a C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, cyano, hydroxy, oxo, halogen, halo-C1-C3 alkyl, hydroxy-C1-C6 alkyl, amino, mono or di-(C1-C6 alkyl)amino, or phenyl or phenyl(C1-C3 alkanoyl) (wherein phenyl may optionally be substituted with a C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C1-C3 alkyl)amino).

[0076] In certain embodiments of formula (I) or formula (IV) described separately herein, R 7 and R 8 These, together with the nitrogen atoms they bond to, form piperidinyl, piperazinyl, or morpholinyl groups, each of which contains 1 to 4 R atoms. 9 The base may be substituted as desired, where R 9Each of these is independently a C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, cyano, hydroxy, oxo, halogen, halo-C1-C3 alkyl, hydroxy-C1-C6 alkyl, amino, mono or di-(C1-C6 alkyl)amino, or phenyl or phenyl(C1-C3 alkanoyl) (wherein phenyl may optionally be substituted with a C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C1-C3 alkyl)amino).

[0077] In certain embodiments of formula (I) or formula (IV) described separately herein, R 7 and R 8 These, together with the nitrogen atoms they bond to, form piperidinyl, piperazinyl, or morpholinyl groups, each of which contains 1 to 4 R atoms. 9 The base may be substituted as desired, where R 9 Each of these is independently a C1-C3 alkyl, C1-C3 alkoxy, C3-C6 cycloalkyl, cyano, hydroxy, oxo, halogen, halo-C1-C3 alkyl, hydroxy-C1-C3 alkyl, amino, or mono- or di-(C1-C3 alkyl)amino.

[0078] In certain embodiments of formula (I) or formula (IV) described separately herein, R 7 and R 8 These, together with the nitrogen atoms they bond to, form piperidinyl, piperazinyl, or morpholinyl groups, each of which contains 1 to 4 R atoms. 9 The base may be substituted as desired, where R 9 These are independently methyl, ethyl, methoxy, ethoxy, cyano, fluoro, chloro, trifluoromethyl, cyclopropyl, or cyclopropylmethyl.

[0079] In another embodiment, this disclosure relates to formula (IV-A): [ka] [In formula: R 1 is H, C1-C3 alkyl, or C3-C6 cycloalkyl; R 2 R is a phenyl or 5-6 membered heteroaryl group, where phenyl and heteroaryl each have 1-5 R 12 It may be replaced as desired; R 12 Each of these is independently a C1-C4 alkyl, -OR A , -C(O)OR A (C1-C3 alkyl)-OR A ,-C(O)N(R A )2, cyano, or halogen; R A Each of these is independently H, C1-C6 alkyl, or C3-C6 cycloalkyl; R 3 These are C1-C3 alkyl, C3-C6 cycloalkyl, C1-C3 alkenyl, C2-C3 alkynyl, or C5-C6 cycloalkenyl molecules, which may be optionally substituted, polysubstituted, or oversubstituted with fluoropolymers; R 4 is H, halogen, C1-C3 alkyl, C3-C6 cycloalkyl, C1-C3 alkenyl, C2-C3 alkynyl, C5-C6 cycloalkenyl, or cyano, where C1-C3 alkyl and C3-C6 cycloalkyl may each be optionally substituted with 1 to 5 halo groups; R 6 and R 6A This independently represents H or C1-C6 alkyl; R 5A , NR 7 R 8, represents a C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl (C1-C3 alkyl), phenyl, or a 5-6 member heteroaryl, where C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl (C1-C3 alkyl), phenyl, and heteroaryl may each be optionally substituted with 1-3 halogens, halo(C1-C3 alkyl), hydroxy, C1-C3 alkyl, C1-C3 alkoxy, cyano, amino, or mono or di(C1-C3)alkylamino; R 7 represents H or C1-C3 alkyl; R 8 represents H, C1-C6 alkyl, C3-C6 cycloalkyl, or C3-C6 cycloalkyl(C1-C3 alkyl), where C1-C6 alkyl, C3-C6 cycloalkyl, and C3-C6 cycloalkyl(C1-C3 alkyl) may be optionally substituted with 1 to 3 halogens, halo(C1-C3 alkyl), hydroxy, C1-C3 alkyl, C1-C3 alkoxy, cyano, amino, or mono or di(C1-C3) alkylamino; or R 7 and R 8 These, together with the nitrogen atoms to which they bond, form a ring Q, where ring Q is A 3-8 membered monocyclic heterocyclyl group, wherein the heterocyclyl group may optionally contain 3-6 ring members, of which 1 or 2 may optionally be nitrogen, oxygen, or sulfur atoms, and the remainder may be carbon, and may be condensed with an aromatic or non-aromatic ring. Alternatively, carbon atoms from a monocyclic heterocyclyl group, along with further carbons and heteroatoms, form a spirocyclic ring system having a total of up to 10 ring members, where the ring members are carbon or heteroatoms selected from one or two nitrogen, sulfur, and oxygen atoms. Here, ring Q has 1 to 4 R in each aromatic or non-aromatic moiety. 9 It may be substituted with the base, where R 9Each of these C1-C6 alkyl groups may be independently and optionally substituted with (i) C1-C6 alkyl, (ii) C1-C6 alkoxy, (iii) C3-C6 cycloalkyl, (iv) cyano, (ii) hydroxy, (v) oxo, (vi) halogen, (vii) halo-C1-C3 alkyl, (viii) hydroxy-C1-C6 alkyl, (ix) amino, (x) mono or di-(C1-C6 alkyl) amino, (xi) one or two C1-C3 alkyl, C1-C3 alkoxy, C3-C6 cycloalkyl, cyano, hydroxy, oxo, halogen, halo-C1-C3 alkyl, hydroxy-C1-C3 alkyl, amino, or mono or di-(C1-C6 alkyl) amino. 2-C6 alkanoyl (where the C1-C3 alkyl or C3-C6 cycloalkyl on the alkanoyl may be optionally substituted with a halogen, hydroxyl, or amino, respectively), (xii) C3-C6 cycloalkyloxy, or (xiii) phenyl, phenyl(C1-C3 alkanoyl), 5-7 membered heterocyclyl, or 5-6 membered heteroaryl (where each phenyl, 5-7 membered heterocyclyl, and 5-6 membered heteroaryl may be optionally substituted with 1-4 C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxyl, cyano, oxo, amino, or mono or di(C1-C3 alkyl)amino) The present invention provides compounds represented by [formula], as well as pharmaceutically acceptable salts, prodrugs, solvates, hydrates, isomers, deuterated forms, and tautomers thereof.

[0080] In another embodiment, this disclosure relates to formula (IV-B): [ka] [In formula: R 1 is H, C1-C3 alkyl, or C3-C6 cycloalkyl; R 2 R is a phenyl or 5-6 membered heteroaryl group, where phenyl and heteroaryl each have 1-5 R 12 It may be replaced as desired; R12 Each of these is independently a C1-C4 alkyl, -OR A , -C(O)OR A (C1-C3 alkyl)-OR A ,-C(O)N(R A )2, cyano, or halogen; R A Each of these is independently H, C1-C6 alkyl, or C3-C6 cycloalkyl; R 3 These are C1-C3 alkyl, C3-C6 cycloalkyl, C1-C3 alkenyl, C2-C3 alkynyl, or C5-C6 cycloalkenyl molecules, which may be optionally substituted, polysubstituted, or oversubstituted with fluoropolymers; R 4 is H, halogen, C1-C3 alkyl, C3-C6 cycloalkyl, C1-C3 alkenyl, C2-C3 alkynyl, C5-C6 cycloalkenyl, or cyano, where C1-C3 alkyl and C3-C6 cycloalkyl may each be optionally substituted with 1 to 5 halo groups; R 6 and R 6A This independently represents H or C1-C6 alkyl; R 5A , NR 7 R 8 , represents a C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl (C1-C3 alkyl), phenyl, or a 5-6 member heteroaryl, where C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl (C1-C3 alkyl), phenyl, and heteroaryl may each be optionally substituted with 1-3 halogens, halo(C1-C3 alkyl), hydroxy, C1-C3 alkyl, C1-C3 alkoxy, cyano, amino, or mono or di(C1-C3)alkylamino; R 7 represents H or C1-C3 alkyl; R 8represents H, C1-C6 alkyl, C3-C6 cycloalkyl, or C3-C6 cycloalkyl(C1-C3 alkyl), where C1-C6 alkyl, C3-C6 cycloalkyl, and C3-C6 cycloalkyl(C1-C3 alkyl) may be optionally substituted with 1 to 3 halogens, halo(C1-C3 alkyl), hydroxy, C1-C3 alkyl, C1-C3 alkoxy, cyano, amino, or mono or di(C1-C3) alkylamino; or R 7 and R 8 These, together with the nitrogen atoms to which they bond, form a ring Q, where ring Q is A 3-8 membered monocyclic heterocyclyl group, wherein the heterocyclyl group may optionally contain 3-6 ring members, of which 1 or 2 may optionally be nitrogen, oxygen, or sulfur atoms, and the remainder may be carbon, and may be condensed with an aromatic or non-aromatic ring. Alternatively, carbon atoms from a monocyclic heterocyclyl group, along with further carbons and heteroatoms, form a spirocyclic ring system having a total of up to 10 ring members, where the ring members are carbon or heteroatoms selected from one or two nitrogen, sulfur, and oxygen atoms. Here, ring Q has 1 to 4 R in each aromatic or non-aromatic moiety. 9 The base may be substituted as desired, where R 9Each of these C2 atoms may be independently substituted as desired with (i) C1-C6 alkyl, (ii) C1-C6 alkoxy, (iii) C3-C6 cycloalkyl, (iv) cyano, (ii) hydroxy, (v) oxo, (vi) halogen, (vii) halo-C1-C3 alkyl, (viii) hydroxy-C1-C6 alkyl, (ix) amino, (x) mono or di-(C1-C6 alkyl)amino, (xi) one or two C1-C3 alkyl, C1-C3 alkoxy, C3-C6 cycloalkyl, cyano, hydroxy, oxo, halogen, halo-C1-C3 alkyl, hydroxy-C1-C3 alkyl, amino, or mono or di-(C1-C6 alkyl)amino. -C6 alkanoyl (wherein the C1-C3 alkyl or C3-C6 cycloalkyl on the alkanoyl, each may optionally be substituted with a halogen, hydroxyl, or amino), (xii)C3-C6 cycloalkyloxy, or (xiii)phenyl, phenyl(C1-C3 alkanoyl), 5-7 membered heterocyclyl, or 5-6 membered heteroaryl (wherein each phenyl, 5-7 membered heterocyclyl, and 5-6 membered heteroaryl may optionally be substituted with 1-4 C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxyl, cyano, oxo, amino, or mono or di(C1-C3 alkyl)amino) The present invention provides compounds represented by [formula], as well as pharmaceutically acceptable salts, prodrugs, solvates, hydrates, isomers, deuterated forms, and tautomers thereof.

[0081] In another embodiment, this disclosure relates to formula (IV-C): [ka] [In formula: R 1 is H, C1-C3 alkyl, or C3-C6 cycloalkyl; R 2 R is a phenyl or 5-6 membered heteroaryl group, where phenyl and heteroaryl each have 1-5 R 12 It may be replaced as desired; R12 Each of these is independently a C1-C4 alkyl, -OR A , -C(O)OR A (C1-C3 alkyl)-OR A ,-C(O)N(R A )2, cyano, or halogen; R A Each of these is independently H, C1-C6 alkyl, or C3-C6 cycloalkyl; R 3 These are C1-C3 alkyl, C3-C6 cycloalkyl, C1-C3 alkenyl, C2-C3 alkynyl, or C5-C6 cycloalkenyl molecules, which may be optionally substituted, polysubstituted, or oversubstituted with fluoropolymers; R 4 is H, halogen, C1-C3 alkyl, C3-C6 cycloalkyl, C1-C3 alkenyl, C2-C3 alkynyl, C5-C6 cycloalkenyl, or cyano, where C1-C3 alkyl and C3-C6 cycloalkyl may each be optionally substituted with 1 to 5 halo groups; R 6 and R 6A This independently represents H or C1-C6 alkyl; R 5A , NR 7 R 8 , represents a C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl (C1-C3 alkyl), phenyl, or a 5-6 membered heteroaryl, where C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl (C1-C3 alkyl), phenyl, and heteroaryl may each be optionally substituted with 1-3 halogens, halo(C1-C3 alkyl), hydroxy, C1-C3 alkyl, C1-C3 alkoxy, cyano, amino, or mono or di(C1-C3)alkylamino; R 7 represents H or C1-C3 alkyl; R 8is H, C1-C6 alkyl, C3-C6 cycloalkyl, or C3-C6 cycloalkyl(C1-C3 alkyl), where C1-C6 alkyl, C3-C6 cycloalkyl, and C3-C6 cycloalkyl(C1-C3 alkyl) may be optionally substituted with 1 to 3 halogens, halo(C1-C3 alkyl), hydroxy, C1-C3 alkyl, C1-C3 alkoxy, cyano, amino, or mono or di(C1-C3) alkylamino; or R 7 and R 8 These, together with the nitrogen atoms to which they bond, form a ring Q, where ring Q is A 3-8 membered monocyclic heterocyclyl group, wherein the heterocyclyl group may optionally contain 3-6 ring members, of which 1 or 2 may optionally be nitrogen, oxygen, or sulfur atoms, and the remainder may be carbon, and may be condensed with an aromatic or non-aromatic ring. Alternatively, carbon atoms from a monocyclic heterocyclyl group, along with further carbons and heteroatoms, form a spirocyclic ring system having a total of up to 10 ring members, where the ring members are carbon or heteroatoms selected from one or two nitrogen, sulfur, and oxygen atoms. Here, ring Q has 1 to 4 R in each aromatic or non-aromatic moiety. 9 It may be substituted with the base, where R 9Each of these C2 atoms may be independently substituted as desired with (i) C1-C6 alkyl, (ii) C1-C6 alkoxy, (iii) C3-C6 cycloalkyl, (iv) cyano, (ii) hydroxy, (v) oxo, (vi) halogen, (vii) halo-C1-C3 alkyl, (viii) hydroxy-C1-C6 alkyl, (ix) amino, (x) mono or di-(C1-C6 alkyl)amino, (xi) one or two C1-C3 alkyl, C1-C3 alkoxy, C3-C6 cycloalkyl, cyano, hydroxy, oxo, halogen, halo-C1-C3 alkyl, hydroxy-C1-C3 alkyl, amino, or mono or di-(C1-C6 alkyl)amino. -C6 alkanoyl (wherein the C1-C3 alkyl or C3-C6 cycloalkyl on the alkanoyl, each may optionally be substituted with a halogen, hydroxyl, or amino), (xii)C3-C6 cycloalkyloxy, or (xiii) phenyl, phenyl(C1-C3 alkanoyl), 5-7 membered heterocyclyl, or 5-6 membered heteroaryl (wherein each phenyl, 5-7 membered heterocyclyl, and 5-6 membered heteroaryl may optionally be substituted with 1-4 C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxyl, cyano, oxo, amino, or mono or di(C1-C3 alkyl)amino) The present invention provides compounds represented by [formula], as well as pharmaceutically acceptable salts, prodrugs, solvates, hydrates, isomers, deuterated forms, and tautomers thereof.

[0082] In another embodiment, this disclosure relates to formula (IV-D): [ka] [In formula: R 1 is H, C1-C3 alkyl, or C3-C6 cycloalkyl; R 2 R is a phenyl or 5-6 membered heteroaryl group, where phenyl and heteroaryl each have 1-5 R 12 It may be replaced as desired; R12 Each of these is independently a C1-C4 alkyl, -OR A , -C(O)OR A (C1-C3 alkyl)-OR A ,-C(O)N(R A )2, cyano, or halogen; R A Each of these is independently H, C1-C6 alkyl, or C3-C6 cycloalkyl; R 3 These are C1-C3 alkyl, C3-C6 cycloalkyl, C1-C3 alkenyl, C2-C3 alkynyl, or C5-C6 cycloalkenyl molecules, which may be optionally substituted, polysubstituted, or oversubstituted with fluoropolymers; R 4 is H, halogen, C1-C3 alkyl, C3-C6 cycloalkyl, C1-C3 alkenyl, C2-C3 alkynyl, C5-C6 cycloalkenyl, or cyano, where C1-C3 alkyl and C3-C6 cycloalkyl may each be optionally substituted with 1 to 5 halo groups; R 6 and R 6A This independently represents H or C1-C6 alkyl; R 5A , NR 7 R 8 , represents a C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl (C1-C3 alkyl), phenyl, or a 5-6 membered heteroaryl, where C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl (C1-C3 alkyl), phenyl, and heteroaryl may each be optionally substituted with 1-3 halogens, halo(C1-C3 alkyl), hydroxy, C1-C3 alkyl, C1-C3 alkoxy, cyano, amino, or mono or di(C1-C3)alkylamino; R 7 represents H or C1-C3 alkyl; R 8represents H, C1-C6 alkyl, C3-C6 cycloalkyl, or C3-C6 cycloalkyl(C1-C3 alkyl), where C1-C6 alkyl, C3-C6 cycloalkyl, and C3-C6 cycloalkyl(C1-C3 alkyl) may be optionally substituted with 1 to 3 halogens, halo(C1-C3 alkyl), hydroxy, C1-C3 alkyl, C1-C3 alkoxy, cyano, amino, or mono or di(C1-C3) alkylamino; or R 7 and R 8 These, together with the nitrogen atoms to which they bond, form a ring Q, where ring Q is A 3-8 membered monocyclic heterocyclyl group, wherein the heterocyclyl group may optionally contain 3-6 ring members, of which 1 or 2 may optionally be nitrogen, oxygen, or sulfur atoms, and the remainder may be carbon, and may be condensed with an aromatic or non-aromatic ring. Alternatively, carbon atoms from a monocyclic heterocyclyl group, along with further carbons and heteroatoms, form a spirocyclic ring system having a total of up to 10 ring members, where the ring members are carbon or heteroatoms selected from one or two nitrogen, sulfur, and oxygen atoms. Here, ring Q has 1 to 4 R in each aromatic or non-aromatic moiety. 9 It may be substituted with the base, where R 9Each of these may be independently substituted with (i) C1-C6 alkyl, (ii) C1-C6 alkoxy, (iii) C3-C6 cycloalkyl, (iv) cyano, (ii) hydroxy, (v) oxo, (vi) halogen, (vii) halo-C1-C3 alkyl, (viii) hydroxy-C1-C6 alkyl, (ix) amino, (x) mono or di-(C1-C6 alkyl)amino, (xi) C2- which may be optionally substituted with one or two C1-C3 alkyl, C1-C3 alkoxy, C3-C6 cycloalkyl, cyano, hydroxy, oxo, halogen, halo-C1-C3 alkyl, hydroxy-C1-C3 alkyl, amino, or mono or di-(C1-C6 alkyl)amino. C6 alkanoyl (wherein the C1-C3 alkyl or C3-C6 cycloalkyl on the alkanoyl, each may optionally be substituted with a halogen, hydroxyl, or amino), (xii) C3-C6 cycloalkyloxy, or (xiii) phenyl, phenyl(C1-C3 alkanoyl), 5-7 membered heterocyclyl, or 5-6 membered heteroaryl (wherein each phenyl, 5-7 membered heterocyclyl, and 5-6 membered heteroaryl may optionally be substituted with 1-4 C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxyl, cyano, oxo, amino, or mono or di(C1-C3 alkyl)amino) The present invention provides compounds represented by [formula], as well as pharmaceutically acceptable salts, prodrugs, solvates, hydrates, isomers, deuterated forms, and tautomers thereof.

[0083] In another embodiment, this disclosure relates to formula (IV-E): [ka] [In formula: R 1 is H, C1-C3 alkyl, or C3-C6 cycloalkyl; R 2 R is a phenyl or 5-6 membered heteroaryl group, where phenyl and heteroaryl each have 1-5 R 12 It may be replaced as desired; R12 Each of these is independently a C1-C4 alkyl, -OR A , -C(O)OR A (C1-C3 alkyl)-OR A ,-C(O)N(R A )2, cyano, or halogen; R A Each of these is independently H, C1-C6 alkyl, or C3-C6 cycloalkyl; R 3 These are C1-C3 alkyl, C3-C6 cycloalkyl, C1-C3 alkenyl, C2-C3 alkynyl, or C5-C6 cycloalkenyl molecules, which may be optionally substituted, polysubstituted, or oversubstituted with fluoropolymers; R 4 is H, halogen, C1-C3 alkyl, C3-C6 cycloalkyl, C1-C3 alkenyl, C2-C3 alkynyl, C5-C6 cycloalkenyl, or cyano, where C1-C3 alkyl and C3-C6 cycloalkyl may each be optionally substituted with 1 to 5 halo groups; RH is bromo, chloro, or fluoro, preferably chloro; R 6 and R 6A This independently represents H or C1-C6 alkyl; R 5A , NR 7 R 8 , C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl (C1-C3 alkyl), phenyl, or 5-6 membered heteroaryl, where C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl (C1-C3 alkyl), phenyl, and heteroaryl may each be optionally substituted with 1-3 halogens, halo(C1-C3 alkyl), hydroxy, C1-C3 alkyl, C1-C3 alkoxy, cyano, amino, or mono or di(C1-C3)alkylamino; R 7 represents H or C1-C3 alkyl; R 8represents H, C1-C6 alkyl, C3-C6 cycloalkyl, or C3-C6 cycloalkyl(C1-C3 alkyl), where C1-C6 alkyl, C3-C6 cycloalkyl, and C3-C6 cycloalkyl(C1-C3 alkyl) may be optionally substituted with 1 to 3 halogens, halo(C1-C3 alkyl), hydroxy, C1-C3 alkyl, C1-C3 alkoxy, cyano, amino, or mono or di(C1-C3) alkylamino; or R 7 and R 8 These, together with the nitrogen atoms to which they bond, form a ring Q, where ring Q is A 3-8 membered monocyclic heterocyclyl group, wherein the heterocyclyl group may optionally contain 3-6 ring members, of which 1 or 2 may optionally be nitrogen, oxygen, or sulfur atoms, and the remainder may be carbon, and may be condensed with an aromatic or non-aromatic ring. Alternatively, carbon atoms from a monocyclic heterocyclyl group, along with further carbons and heteroatoms, form a spirocyclic ring system having a total of up to 10 ring members, where the ring members are carbon or heteroatoms selected from one or two nitrogen, sulfur, and oxygen atoms. Here, ring Q has 1 to 4 R in each aromatic or non-aromatic moiety. 9 It may be substituted with the base, where R 9Each of these C1-C6 alkyl groups may be independently and optionally substituted with (i) C1-C6 alkyl, (ii) C1-C6 alkoxy, (iii) C3-C6 cycloalkyl, (iv) cyano, (ii) hydroxy, (v) oxo, (vi) halogen, (vii) halo-C1-C3 alkyl, (viii) hydroxy-C1-C6 alkyl, (ix) amino, (x) mono or di-(C1-C6 alkyl) amino, (xi) one or two C1-C3 alkyl, C1-C3 alkoxy, C3-C6 cycloalkyl, cyano, hydroxy, oxo, halogen, halo-C1-C3 alkyl, hydroxy-C1-C3 alkyl, amino, or mono or di-(C1-C6 alkyl) amino. 2-C6 alkanoyl (where the C1-C3 alkyl or C3-C6 cycloalkyl on the alkanoyl may optionally be substituted with halogen, hydroxyl, or amino), (xii) C3-C6 cycloalkyloxy, or (xiii) phenyl, phenyl(C1-C3 alkanoyl), 5-7 membered heterocyclyl, or 5-6 membered heteroaryl (where each phenyl, 5-7 membered heterocyclyl, and 5-6 membered heteroaryl may optionally be substituted with 1-4 C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxyl, cyano, oxo, amino, or mono or di(C1-C3 alkyl)amino) The present invention provides compounds represented by [formula], as well as pharmaceutically acceptable salts, prodrugs, solvates, hydrates, isomers, deuterated forms, and tautomers thereof.

[0084] In embodiments of formulas (IV-A) to (IV-E) described separately herein, R 5A is NR 7 R 8 Represents R 7 and R 8 These, together with the nitrogen atoms to which they bond, form a ring Q, where ring Q is A monocyclic heterocyclyl group with 3 to 7 members, The heterocyclyl group has 1 to 4 R 9 The base may be substituted as desired, where R 9Each of these is independently a C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, cyano, hydroxy, oxo, halogen, halo-C1-C3 alkyl, hydroxy-C1-C6 alkyl, amino, mono or di-(C1-C6 alkyl)amino, or phenyl or phenyl(C1-C3 alkanoyl) (wherein phenyl may optionally be substituted with a C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C1-C3 alkyl)amino) (Embodiment (IV-AE-1)).

[0085] In certain embodiments of formulas (IV-A) to (IV-E) described separately herein, R 5A represents piperidinyl, piperazinyl, or morpholinyl, each of which has 1 to 4 R's. 9 The base may be substituted as desired, where R 9 Each of these is independently a C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, cyano, hydroxy, oxo, halogen, halo-C1-C3 alkyl, hydroxy-C1-C6 alkyl, amino, mono or di-(C1-C6 alkyl)amino, or phenyl or phenyl(C1-C3 alkanoyl) (wherein phenyl may optionally be substituted with each of the following: C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C1-C3 alkyl)amino) (Embodiment (IV-AE-2)).

[0086] In specific embodiments of Embodiments (IV-AE-1) and (IV-AE-2), R 2 is phenyl or pyridinyl, each of which has 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A The methyl or ethyl ions are H, methyl, or ethyl.

[0087] In specific embodiments of Embodiments (IV-AE-1) and (IV-AE-2), R2 is phenyl or pyridinyl, each of which has 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A H is H.

[0088] In specific embodiments of Embodiments (IV-AE-1) and (IV-AE-2), R 2 is phenyl or pyridinyl, each of which has 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A It is methyl or ethyl.

[0089] In specific embodiments of Embodiments (IV-AE-1) and (IV-AE-2), R 2 This is 1 to 5 R 12 It is a phenyl compound, which may be substituted as desired.

[0090] In specific embodiments of Embodiments (IV-AE-1) and (IV-AE-2), R 2 This is 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A It is phenyl.

[0091] In specific embodiments of Embodiments (IV-AE-1) and (IV-AE-2), R 2 This is 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A It is phenyl, which is H, methyl, or ethyl.

[0092] In specific embodiments of Embodiments (IV-AE-1) and (IV-AE-2), R 2 This is 1 to 5 R12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A It is phenyl, where H is.

[0093] In specific embodiments of Embodiments (IV-AE-1) and (IV-AE-2), R 2 This is 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A It is phenyl, which is either methyl or ethyl.

[0094] In specific embodiments of Embodiments (IV-AE-1) and (IV-AE-2), R 2 This is 1 to 5 R 12 It is a pyridinyl compound, which may be substituted as desired. In specific embodiments of Embodiments (IV-AE-1) and (IV-AE-2), R 2 This is 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A It is pyridinyl.

[0095] In specific embodiments of Embodiments (IV-AE-1) and (IV-AE-2), R 2 This is 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A It is pyridinyl, where H is methyl or ethyl.

[0096] In specific embodiments of Embodiments (IV-AE-1) and (IV-AE-2), R 2 This is 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here RA It is H, and it is pyridinyl.

[0097] In specific embodiments of Embodiments (IV-AE-1) and (IV-AE-2), R 2 This is 1 to 5 R 12 It may be substituted as desired, and at least one R 12 The base is -C(O)OR A And here R A It is pyridinyl, which is methyl or ethyl.

[0098] In specific embodiments of Embodiments (IV-AE-1) and (IV-AE-2), R 2 The formula is: [ka] [In formula: R 13 Each of these is independently C1-C4 alkyl, -OR B , -C(O)OR B (C1-C3 alkyl)-OR B ,-C(O)N(R B )2, cyano, or halogen; R B Each of these is independently H, C1-C6 alkyl, or C3-C6 cycloalkyl; R 12 is hydrogen, C1-C4 alkyl, -OR A , -C(O)OR A (C1-C3 alkyl)-OR A ,-C(O)N(R A )2, cyano, or halogen; R A Each of these is independently H, C1-C6 alkyl, or C3-C6 cycloalkyl; n is 0, 1, 2, or 3; m is 0, 1, or 2. It is the group shown by .

[0099] In certain embodiments of formulas (4-AE-B) and (4-AE-P), R 12is cyano or halogen. In certain embodiments of formulas (4-AE-B) and (4-AE-P), R 12 is cyano. In certain embodiments of formula (4-AE-B) or formula (4-AE-P), R 12 is fluoro, chloro, or bromo. In other embodiments of formula (4-AE-B) or formula (4-AE-P), R 12 is fluoro or chloro. In other embodiments of formula (4-AE-B) or formula (4-AE-P), R 12 is methyl. In other embodiments of formula (4-AE-B) or formula (4-AE-P), R 12 It is hydrogen.

[0100] In certain embodiments of formula (I) or formula (IV) as described elsewhere herein, the compound is formula (II) or (III): [ka] [In the formula: n is 0, 1, 2, 3, or 4; m is 0, 1, 2, or 3. This is shown.

[0101] In certain embodiments of formula (II) or formula (III) as described elsewhere herein, the compound is formula (II-A): [ka] This is shown.

[0102] In certain embodiments of formula (II) or formula (III) as described elsewhere herein, the compound is of formula (III-A): [ka] This is shown.

[0103] In certain embodiments of formula (II), formula (III), formula (II-A), or formula (III-A) as described elsewhere in this specification, R 1is H, C1-C3 alkyl, or C3-C6 cycloalkyl; R 12 Each of these is independently C1-C4 alkyl;-OR A , -C(O)OR A (C1-C3 alkyl)-OR A ,-C(O)N(R A )2, cyano, or halogen; R A Each of these is independently H, C1-C6 alkyl, or C3-C6 cycloalkyl; R 3 is a C1-C3 alkyl or C3-C6 cycloalkyl; R 4 The group is H, C1-C3 alkyl, C3-C6 cycloalkyl, cyano, or halo, where each C1-C3 alkyl group may optionally be substituted with 1 to 5 halo groups.

[0104] In certain embodiments of formula (II), formula (III), formula (II-A), or formula (III-A) described separately herein, R 3 It is a C1-C3 alkyl group. In certain embodiments of formula (II), formula (III), formula (II-A), or formula (III-A) described separately herein, R 3 It is methyl.

[0105] In certain embodiments of formula (II), formula (III), formula (II-A), or formula (III-A) described separately herein, R 4 The group is H, C1-C3 alkyl, C3-C4 cycloalkyl, or cyano.

[0106] In certain embodiments of formula (II), formula (III), formula (II-A), or formula (III-A) described separately herein, R 7 is hydrogen, R 8 This represents hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, or C3-C6 cycloalkyl (C1-C3 alkyl).

[0107] In certain embodiments of formula (II), formula (III), formula (II-A), or formula (III-A) described separately herein, R 5A is NR 7 R 8 Represents R 7 and R 8 These atoms, together with the nitrogen atoms to which they bind, form ring Q, which is a C1-C6 heterocyclyl.

[0108] In certain embodiments of formula (II), formula (III), formula (II-A), or formula (III-A) described separately herein, R 5A is NR 7 R 8 Represents R 7 and R 8 These, together with the nitrogen they bind to, form ring Q, which is azilidinyl, azetidinyl, pyrrolidinyl, piperazinyl, morpholinyl, piperidinyl, or azepanyl, each of which has 1-2 R 9 The base may be substituted as desired, where R 9 Each of these is independently a C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, cyano, hydroxy, oxo, halogen, halo-C1-C3 alkyl, hydroxy-C1-C6 alkyl, amino, mono or di-(C1-C6 alkyl)amino, phenyl, 5-7 membered heterocyclil, or 5-6 membered heteroaryl, where each of the phenyl, 5-7 membered heterocyclil and 5-6 membered heteroaryl may be optionally substituted with 1-4 C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C1-C3 alkyl)amino.

[0109] In certain embodiments of formula (II), formula (III), formula (II-A), or formula (III-A) described separately herein, R 5A is NR 7 R 8 Represents R 7 and R 8These, together with the nitrogen to which they are bonded, form a ring Q, which is azilidinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or azepanyl, each of which may be optionally substituted with 1, 2, 3, or 4 halogens.

[0110] In certain embodiments of formula (II), formula (III), formula (II-A), or formula (III-A) described separately herein, R 5A is NR 7 R 8 Represents R 7 and R 8 These, together with the nitrogen to which they are bonded, form a ring Q, which is a 5-6 member monocyclic heterocyclyl group that may be fused to an aromatic or non-aromatic ring containing 3-6 ring members, of which 1 or 2 may optionally be nitrogen and the rest may be carbon, and the fused ring system may have 1-4 R 9 The base may be substituted as desired, where R 9 Each of these is independently a C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, cyano, hydroxy, oxo, halogen, halo-C1-C3 alkyl, hydroxy-C1-C6 alkyl, amino, or mono or di-(C1-C6 alkyl)amino.

[0111] In certain embodiments of formula (II), formula (III), formula (II-A), or formula (III-A) described separately herein, R 5A is NR 7 R 8 Represents R 7 and R 8 These, together with the nitrogen atoms to which they bond, form a ring Q, where ring Q is given by formula: [ka] [In formula: Each ring A is a 3- to 6-membered carbon ring or a 3- to 6-membered heterocyclic ring. m is 0, 1, 2, 3, or 4; n is 0, 1, or 2; p and r are independently 1 or 2, provided that the sum of p and r is 2 or 3; R 10 and R 11 Each of these is independently a C1-C6 alkyl, C1-C6 alkoxy, halogen, cyano, hydroxy, hydroxy C1-C6 alkyl, amino, mono or di(C1-C6 alkyl)amino, C3-C6 cycloalkyl, phenyl, or a 5-6 member heteroaryl, where cycloalkyl, phenyl, and heteroaryl may each be optionally substituted with 1-3 halogens, hydroxy, C1-C3 alkyl, C1-C3 alkoxy, cyano, amino, or mono or di(C1-C3) alkylamino. It is the group shown by .

[0112] In certain embodiments of formula (II), formula (III), formula (II-A), or formula (III-A) described separately herein, R 7 and R 8 These, together with the nitrogen atoms to which they are bonded, form piperidinyl, piperazinyl, or morpholinyl groups, each of which contains 1 to 4 R atoms. 9 The base may be substituted as desired, where R 9 Each of these is independently a C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, cyano, hydroxy, oxo, halogen, halo-C1-C3 alkyl, hydroxy-C1-C6 alkyl, amino, mono or di-(C1-C6 alkyl)amino, or phenyl or phenyl(C1-C3 alkanoyl) (where each phenyl may be optionally substituted with a C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C1-C3 alkyl)amino).

[0113] In certain embodiments of formula (II), formula (III), formula (II-A), or formula (III-A) described separately herein, R 7 and R 8These, together with the nitrogen atoms to which they are bonded, form piperidinyl, piperazinyl, or morpholinyl groups, each of which contains 1 to 4 R atoms. 9 The base may be substituted as desired, where R 9 Each of these is independently a C1-C3 alkyl, C1-C3 alkoxy, C3-C6 cycloalkyl, cyano, hydroxy, oxo, halogen, halo-C1-C3 alkyl, hydroxy-C1-C3 alkyl, amino, or mono- or di-(C1-C3 alkyl)amino.

[0114] In certain embodiments of formula (II), formula (III), formula (II-A), or formula (III-A) described separately herein, R 7 and R 8 These, together with the nitrogen atoms to which they are bonded, form piperidinyl, piperazinyl, or morpholinyl groups, each of which contains 1 to 4 R atoms. 9 The base may be substituted as desired, where R 9 These are, independently, methyl, ethyl, methoxy, ethoxy, cyano, fluoro, chloro, trifluoromethyl, cyclopropyl, or cyclopropylmethyl.

[0115] In certain embodiments of formulas (I), (II), (III), (II-A), or (III-A) described separately herein, R 7 and R 8 These, together with the nitrogen atoms to which they bond, form a ring Q, where ring Q is [ka] This represents a more selected nitrogen-containing ring, where v represents 0, 1, 2, 3, or 4, respectively.

[0116] In certain embodiments, the nitrogen-containing ring is independently substituted with one, two, or three halogens. In certain embodiments, the halogens are independently fluorine atoms or chlorine atoms. In certain embodiments, the nitrogen-containing ring is substituted with a phenyl or phenyl(C1-C3 alkanoyl) group, where phenyl may be optionally substituted with a C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C1-C3 alkyl)amino group, respectively.

[0117] In certain embodiments of formulas (I), (II), (III), (II-A), or (III-A) described separately herein, R 5A The formula is: [ka] [In formula: v is independently 0, 1, 2, 3, or 4; R 18 [is H or C1-C6 alkyl] It is the group shown by .

[0118] In certain embodiments, the nitrogen-containing ring is independently substituted with one, two, or three halogens. In certain embodiments, the halogens are independently fluorine atoms or chlorine atoms. In certain embodiments, the nitrogen-containing ring is substituted with a phenyl or phenyl(C1-C3 alkanoyl) group, where phenyl may be optionally substituted with a C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C1-C3 alkyl)amino group, respectively.

[0119] In certain embodiments of formula (I) or formula (IV) described separately herein, R 7 and R 8 These, together with the nitrogen atoms to which they bond, form a ring Q, where ring Q is One or two ring nitrogen atoms form a 3- to 7-membered monocyclic heterocyclyl group containing only nitrogen heteroatoms. The heterocyclyl group contains 3 to 6 ring members, of which 1 or 2 may optionally be nitrogen atoms and the rest may be carbon atoms, and is condensed to an aromatic or non-aromatic ring, where The condensed heterocyclyl group has 1 to 4 R groups in the aromatic or non-aromatic moiety. 9 The base may be substituted as desired, where R 9 Each of these is independently a C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, cyano, hydroxy, oxo, halogen, halo-C1-C3 alkyl, hydroxy-C1-C6 alkyl, amino, mono or di-(C1-C6 alkyl)amino, or phenyl or phenyl(C1-C3 alkanoyl) (where each phenyl may be optionally substituted with a C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C1-C3 alkyl)amino).

[0120] In certain embodiments of formula (I) or formula (IV) described separately herein, R 7 and R 8 These, together with the nitrogen atoms to which they bond, form a ring Q, where ring Q is [ka] Represents a more selected condensed bicyclic group, where each v represents 0, 1, 2, 3, or 4, and R 9 The base can be on any of the rings.

[0121] In certain embodiments, the condensed bicyclic group is independently substituted with 1, 2, 3, or 4 C1-C4 alkyl, C3-C6 cycloalkyl, C1-C3 haloalkyl, or halogen groups. In certain embodiments, the condensed bicyclic group is independently substituted with one, two, three, or four halogens. In certain embodiments, the halogens are independently fluorine atoms or chlorine atoms. In other embodiments, the halogen is a fluorine atom.

[0122] In other embodiments, the condensed bicyclic group is substituted with a phenyl or phenyl(C1-C3 alkanoyl) group, where phenyl may be optionally substituted with a C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C1-C3 alkyl)amino group, respectively.

[0123] In certain embodiments of formula (I) or formula (IV) described separately herein, R 7 and R 8 These, together with the nitrogen atoms to which they are bonded, form a 3-7 member monocyclic heterocyclyl group containing only nitrogen heteroatoms, with one or two ring nitrogen atoms. The heterocyclyl group, together with the carbon atom from the monocyclic heterocyclyl group and further carbon, nitrogen, oxygen, or sulfur atoms, forms a spirocyclic ring system with a total of up to 10 ring members, where The spirocyclic ring system has 1 to 4 R 9 The base may be substituted as desired, where R 9 Each of these is independently a C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, cyano, hydroxy, oxo, halogen, halo-C1-C3 alkyl, hydroxy-C1-C6 alkyl, amino, mono or di-(C1-C6 alkyl)amino, or phenyl or phenyl(C1-C3 alkanoyl) (where each phenyl may be optionally substituted with a C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C1-C3 alkyl)amino).

[0124] In certain embodiments of formula (I) or formula (IV) described separately herein, R 7 and R 8 This represents a spirocyclic ring system having up to 10 ring members in total, with together with the nitrogen to which they are bonded, having one or two heteroatoms selected from nitrogen, oxygen, and sulfur, preferably nitrogen and oxygen. The spirocyclic ring system may have up to 4 R 9 The base may be substituted as desired. An example of such a spirocyclic ring system, which may be substituted as desired, is [ka] Here, v is 0, 1, 2, 3, or 4, respectively, and R 9 The base can be on any ring.

[0125] In certain embodiments, the spirocyclic ring system is independently substituted with 1, 2, 3, or 4 C1-C4 alkyl, C3-C6 cycloalkyl, C1-C3 haloalkyl, or halogen atoms.

[0126] In certain embodiments, the spirocyclic ring system is independently substituted with one, two, three, or four halogens. In certain embodiments, the halogens are independently fluorine atoms or chlorine atoms. In other embodiments, the halogens are fluorine atoms.

[0127] In certain embodiments, the spirocyclic ring system is substituted with a phenyl or phenyl(C1-C3 alkanoyl) group, where phenyl may be optionally substituted with a C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C1-C3 alkyl)amino group.

[0128] In certain embodiments of formulas (I), (II), (III), (IV), (II-A), or (III-A) described separately herein, R 9 is a 5-6 member heteroaryl group which may be optionally substituted. Suitable examples of heteroaryl groups are pyrazolyl, thiazolyl, imidazolyl, pyridinyl, oxazolyl, and isoxazolyl, each of which may be optionally substituted with 1 to 4 C1-C3 alkyl, C1-C3 alkoxy, halogen, hydroxy, cyano, oxo, amino, or mono or di(C1-C3 alkyl)amino groups.

[0129] In a particular embodiment, R 3The stereochemical orientation in is such that the compound will have the stereochemical designation "R" at its position according to the Cahn-Ingold-Prelogue priority rule. Thus, for example, the compound is given by formula (I-1): [ka] [In the formula, the base is as described above for formula (I)] This is shown.

[0130] In certain embodiments of formula (I) or formula (IV) as described elsewhere herein, the compound is formula (II-A-1) or (III-A-1): [ka] [In the formula, n is 0, 1, 2, 3, or 4; m is 0, 1, 2, or 3. This is shown.

[0131] In a particular embodiment of formula (I), the compound is of formula (II-A-1.1) or (III-A-1.1): [ka] [In formula: R 13 Each of these is independently C1-C4 alkyl, -OR B , -C(O)OR B (C1-C3 alkyl)-OR B ,-C(O)N(R B )2, cyano, or halogen; R B Each of these is independently H, C1-C6 alkyl, or C3-C6 cycloalkyl; R 12 is hydrogen, C1-C4 alkyl, -OR A , -C(O)OR A (C1-C3 alkyl)-OR A ,-C(O)N(R A )2, cyano, or halogen; RA Each of these is independently H, C1-C6 alkyl, or C3-C6 cycloalkyl; n is 0, 1, 2, or 3; m is 0, 1, or 2. This is shown.

[0132] In certain embodiments of formulas (II-A-1.1) and (III-A-1.1), R 12 is cyano or halogen. In other embodiments of formula (II-A-1.1) and formula (III-A-1.1), R 12 is cyano. In other embodiments of formula (II-A-1.1) or (III-A-1.1), R 12 is fluoro, chloro, or bromo. In other embodiments of formula (II-A-1.1) or (III-A-1.1), R 12 is fluoro or chloro. In other embodiments of formula (II-A-1.1) or (III-A-1.1), R 12 is methyl. In other embodiments of formula (II-A-1.1) or (III-A-1.1), R 12 It is hydrogen.

[0133] In certain embodiments of formulas (II-A-1.1) and (III-A-1.1), n ​​and m are 1, and R 13 R is hydrogen, methyl, or ethyl. 12 is cyano or halogen. In other embodiments of formula (II-A-1.1) and formula (III-A-1.1), n ​​and m are 1, and R 13 is hydrogen, methyl or ethyl, and R 12 is cyano. In other embodiments of formula (II-A-1.1) or (III-A-1.1), n ​​and m are 1, and R 13 is hydrogen, methyl or ethyl, and R 12 is fluoro, chloro, or bromo. In embodiments of formula (II-A-1.1) or (III-A-1.1), n ​​and m are 1, and R 13 is hydrogen, methyl or ethyl, and R 12 It is fluoro or chloro.

[0134] In certain embodiments of formulas (II-A-1.1) and (III-A-1.1), R 5 is methyl, n and m are 1, and R 13 is hydrogen, methyl or ethyl, iR 12 Is it cyano or halogen? ii.R 12 Is it cyano? iii.R 12 is fluoro, chloro or bromo; or iv.R 12 It is fluoro or chloro.

[0135] In certain embodiments of formulas (II-A-1.1) and (III-A-1.1), R 5 is ethyl, n and m are 1, and R 13 is hydrogen, methyl or ethyl, iR 12 Is it cyano or halogen? ii.R 12 Is it cyano? iii.R 12 is fluoro, chloro or bromo; or iv.R 12 It is fluoro or chloro.

[0136] In certain embodiments of formulas (II-A-1.1) and (III-A-1.1), R 5 is cyano, n and m are 1, and R 13 is hydrogen, methyl or ethyl, iR 12 Is it cyano or halogen? ii.R 12 Is it cyano? iii.R 12 is fluoro, chloro or bromo; or iv.R 12 It is fluoro or chloro.

[0137] In certain embodiments of formulas (II-A-1.1) and (III-A-1.1), R 5 is cyclopropyl, n and m are 1, and R 13 is hydrogen, methyl, or ethyl, iR 12 Is it cyano or halogen? ii.R 12 Is it cyano? iii.R 12 is fluoro, chloro or bromo; or iv.R 12 It is fluoro or chloro.

[0138] In certain embodiments of formulas (II-A-1.1) and (III-A-1.1), R 5 is bromo, n and m are 1, R 13 is hydrogen, methyl or ethyl, iR 12 Is it cyano or halogen? ii.R 12 Is it cyano? iii.R 12 is fluoro, chloro or bromo; or iv.R 12 It is fluoro or chloro.

[0139] In certain embodiments of formulas (II-A-1.1) and (III-A-1.1), R 5 is fluoro, n and m are 1, R 13 is hydrogen, methyl or ethyl, iR 12 Is it cyano or halogen? ii.R 12 Is it cyano? iii.R 12 is fluoro, chloro or bromo; or iv.R 12 It is fluoro or chloro.

[0140] In certain embodiments of formulas (II-A-1.1) and (III-A-1.1), R 5 is chloro, n and m are 1, and R 13 is hydrogen, methyl or ethyl, iR 12 Is it cyano or halogen? ii.R 12 Is it cyano? iii.R 12 is fluoro, chloro or bromo; or iv.R 12 It is fluoro or chloro.

[0141] In certain embodiments of formulas (II-A-1.1) and (III-A-1.1), R 5 is trifluoromethyl, n and m are 1, and R 13 is hydrogen, methyl or ethyl, iR 12 Is it cyano or halogen? ii.R 12 Is it cyano? iii.R 12 is fluoro, chloro or bromo; or iv.R 12 It is fluoro or chloro.

[0142] In a particular embodiment of formula (I), R 5 The group is a 3- to 8-membered heterocyclyl group. In these embodiments, the heterocyclyl group can be linked to the parent ring system via carbon atoms in the heterocyclyl ring. Examples of such groups are tetrahydrofuran-3-yl, tetrahydro-2H-pyran-2-yl, morpholin-2-yl, piperidine-4-yl, 3,6-dihydro-2H-pyran-4-yl, and tetrahydro-2H-pyran-4-yl.

[0143] In one embodiment, the compound of formula (I) or formula (IV) is as follows: [Table 1-1] Table 1-2 Table 1-3 Table 1-4

[0144] Table 1-5 Table 1-6 Table 1-7 Table 1-8

[0145] Table 1-9 Table 1-10 Table 1-11 Table 1-12

[0146] Table 1-13 Table 1-14 Table 1-15 Table 1-16

[0147] [Table 1-17] [Table 1-18] [Table 1-19] [Table 1-20]

[0148] [Table 1-21] [Table 1-22] [Table 1-23] More likely to be selected.

[0149] In one embodiment, the compound of formula (I) is: [Table 2-1] [Table 2-2] [Table 2-3] [Table 2-4]

[0150] [Table 2-5] [Table 2-6] [Table 2-7] Table 2-8

[0151] Table 2-9 Table 2-10 Table 2-11 Table 2-12

[0152] Table 2-13 Table 2-14 Table 2-15 Table 2-16

[0153] Table 2-17 Table 2-18 Table 2-19 Table 2-20

[0154] Table 2-21 [Table 2-22] [Table 2-23] [Table 2-24] [Table 2-25] More likely to be selected.

[0155] Pharmaceutical composition The compound of formula I can be formulated into a pharmaceutical composition.

[0156] In yet another embodiment, the present invention provides a pharmaceutical composition comprising a PI3Kα inhibitor according to the present invention and a pharmaceutically acceptable carrier, excipient, or diluent. The compounds of the present invention can be formulated by any method known in the art and may be manufactured for administration by any route, including but not limited to parenteral, oral, sublingual, transdermal, topical, intranasal, intratracheal, or intracolonic. In certain embodiments, the compounds of the present invention are administered intravenously in a hospital setting. In certain other embodiments, administration is preferably by oral administration.

[0157] The characteristics of the carrier will depend on the route of administration. As used herein, the term "pharmaceutically acceptable" means a non-toxic material that is compatible with a biological system such as cells, cell cultures, tissues, or organisms and does not interfere with the efficacy of the biological activity of the active ingredient. Thus, the compositions according to the present invention may contain, in addition to the inhibitor, diluents, fillers, salts, buffers, stabilizers, solubilizers, and other materials well known in the art. The manufacture of pharmaceutically acceptable formulations is described, for example, in Remington's Pharmaceutical Sciences, 18th Edition, edited by A. Gennaro, Mack Publishing Co., Easton, Pa., 1990.

[0158] As used herein, the term “pharmaceutically acceptable salt” means a salt that retains the desired biological activity of the above-mentioned compound and exhibits minimal or no undesirable toxic effects. Examples of such salts include, but are not limited to, acid addition salts formed with inorganic acids (e.g., hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, etc.), and salts formed with organic acids such as acetic acid, oxalic acid, tartaric acid, succinic acid, malic acid, ascorbic acid, benzoic acid, tannic acid, pamoic acid, alginic acid, polyglutamic acid, naphthalenesulfonic acid, naphthalenedisulfonic acid, and polygalacturonic acid. The compound is also known to those skilled in the art, specifically of formula:-NR + Z - (wherein R is hydrogen, alkyl or benzyl, and Z is a quaternary ammonium salt represented by a chloride, bromide, iodide, --O-alkyl, toluenesulfonate, methylsulfonate, sulfonate, phosphate, or carboxylate (counterions including benzoate, succinate, acetate, glycolate, maleate, citrate, tartrate, ascorbate, benzoate, cinnamoate, mandeloate, benzyloate, and diphenylacetate) which may be administered as a pharmaceutically acceptable quaternary salt.

[0159] The active compound is contained in a pharmaceutically acceptable carrier or diluent in an amount sufficient to deliver a therapeutically effective dose to the patient without causing serious toxicity in the patient being treated. The dose of the active compound for all the symptoms described above ranges from about 0.01 to 300 mg / kg per day, preferably 0.1 to 100 mg / kg, and more generally from 0.5 to about 25 mg per kg of the recipient's body weight per day. A typical topical dose would range from 0.01 to 3% by weight in a suitable carrier. The effective dose range of a pharmaceutically acceptable derivative can be calculated based on the weight of the parent compound to be delivered. If the derivative is active on its own, the effective dose can be estimated as described above using the weight of the derivative or by other means known to those skilled in the art.

[0160] A pharmaceutical composition containing the compound of the present invention may be used in the manner described herein. How to use In yet another embodiment, the disclosure relates generally to methods for treating cancer. These methods include administering an effective amount of a PI3K inhibitor (e.g., a PI3Kα inhibitor or an inhibitor of a PI3Kα H1047R variant) to the target of interest.

[0161] In some embodiments, the PI3K inhibitor (e.g., a PI3Kα inhibitor or an inhibitor of the PI3KαH1047R variant) is a compound of formula (I), (IIa), (IIb), (IIc), or a pharmaceutically acceptable salt thereof, prodrug, solvate, hydrate, isomer, or tautomer. In certain embodiments, the PI3K inhibitor includes compounds selected from Table 1.

[0162] In yet another embodiment, the Disclosure provides compounds that can be obtained by methods for producing the compounds described herein (for example, methods comprising one or more steps described in the scheme), or compounds obtained by such methods.

[0163] In yet another embodiment, the present disclosure provides a pharmaceutical composition comprising a compound of formula (I), (IIa), (IIb), (IIc), or a pharmaceutically acceptable salt thereof, prodrug, solvate, hydrate, isomer, or tautomer, and a pharmaceutically acceptable diluent or carrier.

[0164] In yet another embodiment, the present disclosure provides an intermediate described herein (for example, selected from the intermediates described in the Examples) that is suitable for use in a method for producing the compounds described herein.

[0165] In yet another embodiment, the present disclosure provides a method for modulating PI3K (e.g., PI3Kα) activity (e.g., in vitro or in vivo) by contacting cells with a therapeutically effective amount of a compound of formula (I), (IIa), (IIb), (IIc), or a pharmaceutically acceptable salt, prodrug, solvate, hydrate, isomer, or tautomer thereof.

[0166] In certain embodiments, PI3K-related diseases or disorders include the H1047R mutation. For example, in certain embodiments described separately herein, a compound exhibits high selectivity for inhibiting H1047R-mutated PI3Kα compared to wild-type PI3Kα. This unexpected finding suggests that certain compounds may enable targeted inhibition of PI3Kα through a novel binding mechanism compared to conventional wild-type PI3Kα inhibitors. While not theoretically bound, the H1047R-mutated PI3Kα has modifications at a site far removed from the active site of wild-type PI3Kα. Therefore, it is unlikely that a compound selective for H1047R-mutated PI3Kα compared to wild-type PI3Kα would strongly bind to the PI3Kα active site; rather, it would be advantageous to target other binding pockets. Since the active site of PI3K-type proteins is thought to be better conserved among different mutants, compounds that effectively bind to a site other than the active site may offer higher selectivity for inhibiting PI3Kα compared to other PI3K proteins such as PI3Kβ.

[0167] In yet another embodiment, a method for treating cancer is provided, comprising administering to a cancer patient a therapeutically effective amount of a compound of formula I, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof.

[0168] The compositions and methods provided herein may be used to treat a wide range of cancers, including tumors such as prostate cancer, breast cancer, brain cancer, skin cancer, cervical cancer, testicular cancer, and the like. More specifically, cancers that can be treated by the compositions and methods of the present invention include, but are not limited to, astrocytic cell carcinoma, breast cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, gastric cancer, head and neck cancer, hepatocellular carcinoma, pharyngeal cancer, lung cancer, oral cancer, ovarian cancer, prostate cancer, and thyroid cancer and sarcoma. More specifically, these compounds include: heart: sarcomas (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyosarcoma, fibroma, lipoma, and teratoma; lung: bronchial cancer (squamous cell carcinoma, anaplastic small cell carcinoma, anaplastic large cell carcinoma, adenocarcinoma), alveolar (bronchiolar) adenocarcinoma, bronchial adenoma, sarcoma, lymphoma, chondrotoxic hamartoma, mesothelioma; digestive tract: esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas Pancreatic ductal adenocarcinoma, insulinoma, glycagonoma, gastrinoma, carcinoid tumor, bipoma; small intestine (adenocarcinoma, lymphoma, carcinoid tumor, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma); large intestine (adenocarcinoma, tubular adenoma, chorioadenoma, hamartoma, leiomyoma); urogenital system: kidney (adenocarcinoma, Wilms' tumor (nephroblastoma), lymphoma, leukemia), bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma) Prostate (adenocarcinoma, sarcoma), testes (seminocarcinoma, teratoma, fetal carcinoma, teratoma, choriocarcinoma, sarcoma, stromal cell carcinoma, fibroma, fibroadenoma, adenomatous tumor, lipoma); Liver: liver tumor (hepatocellular carcinoma), cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma; Biliary tract: gallbladder cancer, ampullary carcinoma, cholangiocarcinoma; Bone: osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticular cell sarcoma), multiple bone marrow Tumors, malignant giant cell tumors, chordomas, osteochondromas (osteochondrial exostomas), benign chondromas, chondroblastomas, chondromyxofibromas, osteoids, and giant cell tumors; nervous system: skull (osteomas, hemangiomas, granulomas, xanthomas, osteoosteitis), meninges (meningiomas, meningiosarcomas, gliomas), brain (astrocytomas, medulloblastomas, gliomas, epitheliomas, germ cell tumors (pineal glandomas), glioblastoma multiforme, oligodendroglioma, schwannomas, retinoblastomas, congenital tumors), spinal neurofibromas, meningiomas, gliomas, sarcomas);Gynecology: Uterus (endometrial cancer), cervix (cervical cancer, preneoplastic cervical dysplasia), ovaries (ovarian cancer (serous cystadenocarcinoma, mucinous cystadenocarcinoma, undifferentiated carcinoma), granulosa cell tumor, Sertoli-Leydig tumor, undifferentiated germ cell tumor, malignant teratoma), vulva (squamous cell carcinoma, carcinoma in situ, adenocarcinoma, fibrosarcoma, melanoma), vagina (clear cell carcinoma, squamous cell carcinoma, staphyloid sarcoma (embryonic rhabdomyosarcoma), fallopian tube (cancer); Hematology: Blood (myeloid leukemia (acute y It can be used to treat diffuse lymphocytic leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative disorders, multiple myeloma, myelodysplastic syndromes, Hodgkin's disease, non-Hodgkin lymphoma (malignant lymphoma); skin: malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, dysplastic nevus moles, lipomas, hemangiomas, dermatofibromas, keloids, psoriasis; and adrenal glands: neuroblastoma. In certain embodiments, the cancer is diffuse large B-cell lymphoma (DLBCL).

[0169] In one embodiment, the cancer is selected from hepatocellular carcinoma, breast cancer, skin cancer, bladder cancer, liver cancer, pancreatic cancer, and head and neck cancer. In yet another embodiment, the cancer is selected from breast cancer, uterine carcinosarcoma, endometrial cancer, colorectal adenocarcinoma, gastric adenocarcinoma, head and neck squamous cell carcinoma, bile duct cancer, esophageal adenocarcinoma, bladder cancer, lung squamous cell carcinoma, glioma, adrenocortical carcinoma, hepatocellular carcinoma, sarcoma, prostate adenocarcinoma, renal cell carcinoma, lung adenocarcinoma, ovarian cystadenocarcinoma, glioblastoma multiforme, and melanoma.

[0170] Thus, in certain embodiments, the present disclosure provides a method for treating cancer, comprising administering a compound of formula (I), a pharmaceutical composition thereof, and a KRAS inhibitor to a patient in need thereof, wherein the cancer is breast cancer, uterine carcinosarcoma, endometrial cancer, colorectal adenocarcinoma, gastric adenocarcinoma, head and neck squamous cell carcinoma, bile duct cancer, esophageal adenocarcinoma, bladder cancer, lung squamous cell carcinoma, glioma, adrenocortical carcinoma, hepatocellular carcinoma, sarcoma, prostate adenocarcinoma, renal cell carcinoma, lung adenocarcinoma, ovarian cystadenocarcinoma, glioblastoma multiforme, and melanoma.

[0171] In other embodiments, the present disclosure provides a method for treating cancer, comprising administering a compound of formula (I), a pharmaceutical composition thereof, and a variant selective KRAS inhibitor to a patient in need thereof, wherein the cancer is breast cancer, uterine carcinosarcoma, endometrial cancer, colorectal adenocarcinoma, gastric adenocarcinoma, head and neck squamous cell carcinoma, cholangiocarcinoma, esophageal adenocarcinoma, bladder cancer, lung squamous cell carcinoma, glioma, adrenocortical carcinoma, hepatocellular carcinoma, sarcoma, prostate adenocarcinoma, renal cell carcinoma, lung adenocarcinoma, ovarian cystadenocarcinoma, glioblastoma multiforme, or melanoma.

[0172] In yet another embodiment, the present disclosure relates to a compound of formula (I) and a pharmaceutical composition thereof for use in combination with a KRAS inhibitor in the treatment of cancer, wherein the cancer The present invention provides a compound of formula (I) and a pharmaceutical composition thereof, which is used for breast cancer, uterine carcinosarcoma, endometrial cancer, colorectal adenocarcinoma, gastric adenocarcinoma, head and neck squamous cell carcinoma, bile duct cancer, esophageal adenocarcinoma, bladder cancer, lung squamous cell carcinoma, glioma, adrenocortical carcinoma, hepatocellular carcinoma, sarcoma, prostate adenocarcinoma, renal cell carcinoma, lung adenocarcinoma, ovarian cystadenocarcinoma, glioblastoma multiforme, and melanoma.

[0173] The concentration and route of administration to the patient will vary depending on the cancer being treated. The compound, its pharmaceutically acceptable salts, and pharmaceutical compositions containing such compound and salts can be co-administered with other antitumor compounds, such as chemotherapy, or used in combination with other treatments such as radiotherapy or surgical intervention as an adjuvant before or after surgery.

[0174] This disclosure provides a method for treating, preventing or improving a disease or disorder in which PI3K plays a role, comprising administering a therapeutically effective amount of a PI3K inhibitor to a patient in need. The method of this disclosure may be used for the treatment of various PI3K-dependent diseases and disorders.

[0175] In some embodiments, the disease or disorder is cancer (e.g., breast cancer, brain cancer, prostate cancer, endometrial cancer, gastric cancer, leukemia, lymphoma, sarcoma, colorectal cancer, lung cancer, ovarian cancer, skin cancer, and head and neck cancer). In some embodiments, diseases or disorders associated with PI3K include, but are not limited to, CLOVES syndrome (congenital lipomatous hypergrowth, vascular malformations, epidermal nevi, scoliosis / skeletal and spinal syndromes), PIK3CA-associated hypergrowth syndrome (PROS), endometrial cancer, breast cancer, esophageal squamous cell carcinoma, cervical squamous cell carcinoma, cervical adenocarcinoma, colorectal adenocarcinoma, bladder urothelial carcinoma, glioblastoma, ovarian cancer, and non-minor These include cell lung cancer, esophageal and gastric cancer, nerve sheath tumors, squamous cell carcinoma of the head and neck, melanoma, esophageal and gastric adenocarcinoma, soft tissue sarcoma, prostate cancer, fibrous laminae carcinoma, hepatocellular carcinoma, diffuse glioma, colorectal cancer, pancreatic cancer, bile duct cancer, B-cell lymphoma, mesothelioma, adrenocortical carcinoma, non-clear cell renal carcinoma, clear cell renal carcinoma, germ cell carcinoma, thymic tumor, pheochromocytoma, other neuroepithelial tumors, thyroid cancer, leukemia, and encapsulated glioma.

[0176] Details of this disclosure are described in the attached specification below. Methods and materials similar to or equivalent to those described herein may be used in the practice or testing of this disclosure, but only illustrative methods and materials are described here. Other features, purposes, and advantages of this disclosure will be apparent from the specification and claims. In the specification and attached claims, singular nouns also include plural nouns unless the context clearly indicates otherwise. Unless otherwise noted, all technical and scientific terms used herein have the same meaning as that generally understood by those skilled in the art to which this disclosure belongs. All patents and publications cited herein are incorporated herein in their entirety with proper attribution.

[0177] General reaction scheme, intermediates, and examples The compounds of the present invention may be prepared using commercially available reagents and intermediates by the synthesis methods and reaction schemes described herein, or by other reagents and conventional methods well known to those skilled in the art.

[0178] When referring to the "first enantiomer to elute" or the "next enantiomer to elute," unless otherwise specified, the specific stereochemistry of such enantiomers has not been measured, and the stereochemistry shown in the structure of the corresponding compound is arbitrarily assigned. For example, intermediates for producing the compounds of the present invention, and compounds of formula (I) of the present invention, may be produced according to general reaction schemes 1 and 2.

[0179] General reaction scheme 1 [ka] In general reaction scheme 1, the compound 9 This is an example of equation (I). In this general reaction scheme 1, 1 The compound undergoes the formation of an amide bond with an activated acid or acid chloride in the presence of a suitable base such as triethylamine or diisopropylethylamine. 2 This can provide the compound. Condensation to quinoxaline N-oxide is achieved by heating in the presence of a suitable base such as sodium ethoxide, followed by reduction of the N-oxide with a suitable reagent such as phosphorus tribromide, and protection of the compound. 3 The aryl bromide is converted to an acyl group through a palladium-catalyzed reaction such as the Heck reaction or the Still reaction with vinyl ether, and then treated with an aqueous acid to obtain the compound. 4 This can be achieved. Ammonia decomposition is carried out under heating in a suitable solvent such as ammonia in methanol, and the compound 5Compound 6 can be produced by condensing an aryl ketone with an amine supporting a chiral auxiliary, followed by reduction to benzylamine, using a dehydrating agent such as titanium(IV) ethoxide and a hydrogenation transfer agent such as sodium borohydride, sodium cyanoborohydride, lithium aluminum hydride, diisobutylaluminum hydride, or zirconocene hydrochloride. Alternatively, compound 6 can be obtained by asymmetric hydrogenation, transfer hydrogenation, or resolution of a racemic amine. The terminal amide is converted to a nitrile via the action of a dehydrating agent such as phosphorus oxychloride or Burgess reagent, and deprotection of benzylamine is achieved, for example, under a Brønsted or Lewis acidic agent such as hydrochloric acid or trimethylsilyltrifluoromethanesulfonate, and compound 6 is produced. 7 It can be obtained. Benzylamine can be substituted via the action of a palladium or copper catalyst under Buchwald-Hartwig, Ullmann-Goldberg, or Chan-Evans-Lamb reaction conditions using a suitable electrophile or boronic acid, solvent and base, and compound 8 It can be obtained. In addition, compounds 8 It can be obtained via a catalyst-free aromatic nucleophilic substitution reaction with a suitable electrophile at high temperatures in the presence of a suitable base such as diisopropylethylamine. Finally, 9 These compounds can be obtained by deprotecting them under acidic conditions, such as via the action of trifluoroacetic acid, followed by activation via benzotriazole-1-yloxytripyrrolidinophosphonium hexafluorophosphate, phosphorus oxychloride, or other activating reagents, and then reacting them with substituted amines at ambient temperature or high temperature in the presence of a base.

[0180] General reaction scheme 2 [ka] In general reaction scheme 2, the compound 15 This is an example of equation (I). In this general reaction scheme 2, 10 This is reacted in a condensation reaction with an activated alpha-keto acid, an acid halide, or a 2-oxomalonate to form a compound.11 You can obtain it. R 5 In cases where the compound is an ester, the free amide can be obtained by aminolysis using a suitable solvent such as ammonia in methanol at high temperatures. By treating with a suitable chlorinating reagent such as phosphorus oxychloride, the compound can be obtained. 12 Under these conditions, the terminal amide is dehydrated, and R 5 Nitriles will be provided. aryl chloride 12 The compound is reacted with an amine and a suitable base such as diisopropylethylamine at ambient temperature or high temperature. 13 The compound can be produced by subjecting it to a palladium-catalyzed conversion such as a Heck reaction or Still coupling reaction with a suitable vinyl ether partner, and then treating it with an aqueous acid, such as hydrochloric acid. 14 This can be done to obtain the ketone and amine reduction amination using a suitable Lewis acid and a hydride donor such as trimethylsilyltrifluoromethanesulfonate and borane, or other common hydrogenation reducing agents, and the compound 15 It is possible to obtain chiral benzylamines using a reaction scheme similar to general reaction scheme 1, via condensation of chiral amine reagents, subsequent reduction, and carbon-nitrogen bond formation reactions, e.g., Buchwald-Hartwig, Ullmann-Goldberg coupling, Chan-Evans-Lamb coupling, alkylation, nucleophilic aromatic substitution, or reductive amination, and compounds 15 You can obtain this. Intermediate A [ka]

[0181] Step A: To a solution of 2-bromo-4-methyl-6-nitroaniline (540 g, 2.34 mol, 1.00 equivalent) in toluene (650 mL), ethyl 3-chloro-3-oxopropionate (422 g, 2.80 mol, 353 mL, 1.20 equivalent) was added at 0°C, and the reaction mixture was stirred at 110°C for 1 hour. After the reaction was complete, the mixture was cooled to 25°C and poured into petroleum ether (3.00 L). The reaction mixture was filtered, and the filter cake was collected to obtain ethyl 3-((2-bromo-4-methyl-6-nitrophenyl)amino)-3-oxopropionate (790 g, 2.29 mol, yield 97.9%) as a yellow solid. LCMS[M+1] + =344.9

[0182] 1 H NMR (400MHz, CDCl3) δ=9.70(brs,1H), 7.70(d,J=2.0Hz,2H), 4.30(q,J=7.2Hz,2H), 3.51(s,2H), 2.41(s,3H), 1.35(t,J=7.2Hz,3H)

[0183] Step B: To a solution of sodium ethoxide (734 mL, 2.17 M, 2.20 equivalents) in ethanol (500 mL) and tetrahydrofuran (1.50 L), a solution of ethyl 3-((2-bromo-4-methyl-6-nitrophenyl)amino)-3-oxopropionate (250 g, 724 mmol, 1.00 equivalent) in tetrahydrofuran (1.00 L) was added dropwise at -30°C. The reaction mixture was then stirred at -30°C for 15 minutes. After the reaction was complete, the mixture was slowly poured into ice water (5.00 L) at 0°C. The pH of the mixture was then adjusted to approximately pH 4 with hydrogen chloride (4 M in water). The resulting suspension was filtered, and the filter cake was collected to obtain the crude product. The crude product was triturated with acetonitrile (750 mL) at room temperature for 30 minutes. Next, the mixture was filtered, the filtered cake was collected, and dried under reduced pressure to obtain 5-bromo-2-(ethoxycarbonyl)-3-hydroxy-7-methylquinoxaline 1-oxide (190 g, 542 mmol, yield 74.9%, purity 93.4%) as a yellow solid. LCMS[M+3] + =328.9

[0184] 1 H NMR (400MHz, CDCl3) δ=9.67(brs,1H), 8.09(s,1H), 7.71(d,J=1.2Hz,1H), 4.52(q,J=7.2Hz,2H), 2.46(s,3H), 1.43(t,J=6.8Hz,3H)

[0185] Step C: To a solution of 5-bromo-2-(ethoxycarbonyl)-3-hydroxy-7-methylquinoxaline 1-oxide (200 g, 581 mmol, 1.00 equivalent) in DMF (2.50 L), phosphorus tribromide (314 g, 1.16 mol, 110 mL, 2.00 equivalent) was added dropwise at 0°C. The reaction mixture was then stirred at 60°C for 2 hours. The mixture was then cooled to 25°C and poured into ice water (4.00 L). The resulting mixture was filtered, and the filter cake was collected. The filter cake was triturated with acetonitrile (500 mL) at 15°C for 30 minutes. Next, the mixture was filtered, the filtered cake was collected, and dried under reduced pressure to obtain ethyl 5-bromo-3-hydroxy-7-methylquinoxaline-2-carboxylate (150 g, 465 mmol, yield 80.1%, purity 96.5%) as a yellow solid. LCMS[M+1] + =310.9

[0186] 1 H NMR (400MHz, CDCl3) δ=9.54(brs,1H), 7.71(s,1H), 7.66(s,1H), 4.51(q,J=7.2Hz,2H), 2.45(s,3H), 1.44(t,J=7.2Hz,3H)

[0187] Step D: To a solution of ethyl 5-bromo-3-hydroxy-7-methylquinoxaline-2-carboxylate (300 g, 964 mmol, 1.00 equivalent) and potassium carbonate (400 g, 2.89 mol, 3.000 equivalents) in DMF (2.40 L), PMBCl (151 g, 964 mmol, 131 mL, 1.00 equivalent) was added, and the reaction mixture was stirred at 50°C for 8 hours. The reaction mixture was then cooled to 25°C and poured into ice water (4.00 L). The mixture was then filtered, and the filtered cake was collected. The filtration cake was tritulated with acetonitrile (800 mL) at 20°C for 20 minutes, then filtered, the filtration cake was collected again, and dried under reduced pressure to obtain 5-bromo-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-2-carboxylate ethyl (380 g, 819 mmol, yield 85.0%, purity 93.0%) as a yellow solid. LCMS[M+23] + =453.1

[0188] 1 H NMR (400MHz, CDCl3) δ=7.86(s,1H), 7.79(s,1H), 7.56(d,J=8.4Hz,2H), 6.89(d,J=8.4Hz,2H), 5.61 (s,2H), 4.49(q,J=6.8Hz,2H), 3.78(s,3H), 2.49(s,3H), 1.41(t,J=7.2Hz,3H)

[0189] Step E: A mixture of ethyl 5-bromo-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-2-carboxylate (1.00 kg, 2.16 mol, 1.00 equivalent), tributyl(1-ethoxyvinyl)tin (1.00 kg, 2.77 mol, 935 mL, 1.28 equivalent), Pd2(dba)3 (98.7 g, 108 mmol, 0.050 equivalent), and XPhos (51.4 g, 108 mmol, 0.050 equivalent) in toluene (16.0 L) was degassed and purged with nitrogen 2 three times. The reaction mixture was then stirred under a nitrogen atmosphere at 100°C for 5 hours. After the reaction was complete, the mixture was cooled to 25°C, and then a solution of ethyl 5-(1-ethoxyvinyl)-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-2-carboxylate (911 g, crude) in toluene (16.0 L) was obtained as a colored liquid, which was used directly in the next step. LCMS[M+1] + =423.2

[0190] Step F: A solution of ethyl 5-(1-ethoxyvinyl)-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-2-carboxylate (911 g, crude) in toluene (16.0 L) was cooled to 20°C, and tetrahydrofuran (14.0 L) was added. Hydrogen chloride (1.94 L, 1.00 M, 0.900 equivalents) was added dropwise to this mixture at 0°C, and the mixture was stirred at 0°C for 30 minutes. After this time, the pH of the mixture was adjusted to approximately 7 using saturated sodium bicarbonate in water. Potassium fluoride (4.31 L, 4.00 M in water) was added to this mixture. After 1 hour, the mixture was diluted with water (6.00 L) and ethyl acetate (6.00 L). The mixture was then filtered, and the filtrate was extracted with ethyl acetate (5.00 L x 2). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a residue. The residue was triturated with (dichloromethane:ethyl acetate = 1:2, 500 mL) and then further triturated at 20°C for 30 minutes (petroleum ether:ethyl acetate = 3:1, 500 mL). The mixture was then filtered, the filter cake was collected, and dried under reduced pressure to obtain 5-acetyl-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-2-carboxylate ethyl (640 g, 1.51 mol, yield 70.0%) as a yellow solid. LCMS[M+23] + =417.1

[0191] 1 H NMR (400MHz, CDCl3) δ=8.04(d,J=0.8Hz,1H), 7.99(d,J=2.0Hz,1H), 7.42(d,J=8.8Hz,2H), 6.92(d,J=8.4Hz,2H), 5 .53(s,2H), 4.51(q,J=6.8Hz,2H), 3.82(s,3H), 2.93(s,3H), 2.57(s,3H), 1.41(t,J=7.2Hz,3H)

[0192] Step G: Ammonia (130 g, 7.62 mol, 14.6 equivalents) was passed through methanol (1.00 L) at 15°C for 1 hour. Next, the above solution was added to a mixture of 5-acetyl-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-2-carboxylate ethyl (206 g, 522 mmol, 1.00 equivalent) in methanol (2.00 L). The mixture was stirred at 25°C for 16 hours, then concentrated under reduced pressure at 30°C to obtain 5-acetyl-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-2-carboxamide (210 g, 466 mmol, yield 89.1%, purity 81.0%) as a yellow solid. LCMS[M+1] + =366.3

[0193] Step H: A mixture of 5-acetyl-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-2-carboxamide (89.0 g, 244 mmol, 1.00 equivalent) and (R)-2-methylpropane-2-sulfinamide (148 g, 1.22 mol, 5.00 equivalent) in 2-methyltetrahydrofuran (3.00 L) was mixed with titanium(IV) ethoxide (278 g, 1.22 mol, 253 mL, 5.00 equivalent), and the reaction was stirred at 70°C for 24 hours. The mixture was then cooled to 25°C, diluted with ethyl acetate (2.00 L), and quenched using sodium bicarbonate (saturated in water, 1.50 L) at 0°C. Next, the mixture was filtered, the filtrate was washed with water (1.00 L x 2), then with brine (500 mL x 1), dried on anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a residue. The residue was triturated with ethyl acetate (100 mL) at 20°C for 1 hour. Next, the mixture was filtered, the filtration cake was collected, and dried under reduced pressure to obtain (R)-5-(1-((tert-butylsulfinyl)imino)ethyl)-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-2-carboxamide (101 g, 174 mmol, yield 71.4%, purity 80.7%) as a yellow solid. LCMS[M+1] + =469.2

[0194] 1H NMR (400MHz, CDCl3) δ=7.98(s,1H), 7.73(s,1H), 7.59(brs,1H), 7.45-7.42(m,2H), 6.91(brd,J=6.8Hz,2H), 6.23(brs,1H), 5.55(s,2H), 3.81(s,3H), 2.94(d,J=1.6Hz,3H), 2.57(s,3H), 1.23(s,9H)

[0195] Step I: To a solution of (R)-5-(1-((tert-butylsulfinyl)imino)ethyl)-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-2-carboxamide (155 g, 257 mmol, 1.00 equivalent) in dichloromethane (1.50 L) and methanol (1.50 L), acetic acid (77.1 g, 1.28 mol, 73.5 mL, 5.00 equivalent) and sodium cyanoborate (64.5 g, 1.03 mol, 4.00 equivalent) was added at 0°C. The reaction mixture was then stirred at 20°C for 12 hours. After this time, the mixture was washed with water (1.00 L), and the organic layer was slowly treated with sodium bicarbonate (saturated in water, 800 mL) at 0°C. The resulting mixture was washed with water (1.00 L) and brine (500 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 5-((R)-1-(((R)-tert-butylsulfinyl)amino)ethyl)-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-2-carboxamide (155 g, crude product) as a yellow solid. LCMS[M+1] + =471.2

[0196] Step J: To a solution of 5-((R)-1-(((R)-tert-butylsulfinyl)amino)ethyl)-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-2-carboxamide (190 g, 299 mmol, 1.00 equivalent) in THF (2.00 L), hydrogen chloride (380 mL, 1.00 M in water, 1.27 equivalents) was added dropwise at 0°C, and the mixture was stirred at 15°C for 7 hours. After the reaction was complete, a solution of (R)-5-(1-aminoethyl)-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-2-carboxamide (160 g, crude) in THF (2.00 L) was obtained as a yellow liquid, which was used directly in the next step. LCMS[M+1] + =367.1

[0197] Step K: To a solution of ((R)-5-(1-aminoethyl)-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-2-carboxamide (160 g, 288 mmol, 1.00 equivalent) in THF (2.00 L), add sodium hydroxide (34.6 g, 865 mmol, 3.00 equivalent) / water (1.00 L) and Boc2O (75.5 g, 346 mmol, 79.4 mL, 1.20 equivalent), and react the mixture at 50°C for 1 hour. The mixture was stirred throughout this time. After this period, the mixture was diluted with ethyl acetate (1.00 L), washed with brine (500 mL x 2), dried on anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain (R)-(1-(2-carbamoyl-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-5-yl)ethyl) tert-butyl carbamate (160 g, crude product) as a yellow solid. LCMS[M+1] + =467.3

[0198] Step L: To a solution of (R)-(1-(2-carbamoyl-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-5-yl)ethyl)carbamate tert-butyl (215 g, 277 mmol, 1.00 equivalent) in THF (3.00 L), Burgess's reagent (198 g, 830 mmol, 3.00 equivalent) was added at 0°C. The reaction mixture was stirred at 0°C for 1 hour, then diluted with ethyl acetate (1.00 L), and washed with water (500 mL) and brine (500 mL x 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was tritulated with acetonitrile (180 mL) at 20°C for 30 minutes, then filtered, the filtered cake was collected, and dried under reduced pressure to obtain (R)-(1-(2-cyano-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-5-yl)ethyl) tert-butyl carbamate (125 g, 234 mmol, yield 84.7%, purity 84%) as a yellow solid. LCMS[M+23] + =471.3

[0199] 1 H NMR (400MHz, CDCl3) δ=7.73(d,J=0.8Hz,1H), 7.60(d,J=1.6Hz,1H), 7.52-7.47(m,2H), 6.97-6.91(m,2H) ), 5.69-5.40(m,4H), 3.82(s,3H), 2.54(s,3H), 1.53(d,J=6.8Hz,3H), 1.44(brs,9H)

[0200] Step M: To a solution of (R)-(1-(2-cyano-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-5-yl)ethyl)carbamate tert-butyl (300 g, 562 mmol, 1.00 equivalent) in dichloromethane (3.00 L), 2,6-dimethylpyridine (482 g, 4.49 mol, 524 mL, 8.00 equivalent) and trimethylsilyl trifluoromethanesulfonate (500 g, 2.25 mol, 406 mL, 4.00 equivalent) were added. The mixture was then stirred at 40°C for 1 hour, and subsequently diluted with water (2.50 L) at 0°C. The resulting mixture was washed with brine (500 mL x 2), and then with citric acid (1N in water, 1000 mL x 4). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was tritulated with acetonitrile (450 mL) at 20°C for 10 minutes. The mixture was then filtered, the filter cake was collected, and dried under reduced pressure to obtain the crude product. The crude product was purified by reverse-phase flush (column: Sfar C18 1800 g D Duo 30 μm; mobile phase: Phase A: 0.225% formic acid in water, Phase B: acetonitrile; gradient: 35%-65% Phase B) to obtain (R)-5-(1-aminoethyl)-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-2-carbonitrile (195 g, 535 mmol, yield 95.2%, purity 95.6%) as a yellow solid. LCMS[M+1] + =349.1

[0201] 1 H NMR (400MHz, CDCl3) δ=7.71(s,2H), 7.47(d,J=8.4Hz,2H), 6.92(d,J=8.4Hz,2H), 5.55(s,2H), 5.01( q,J=6.8Hz,1H), 3.81(s,3H), 2.69(brs,2H), 2.54(s,3H), 1.55(d,J=6.8Hz,3H)

[0202] In step N, a mixture of (R)-5-(1-aminoethyl)-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-2-carbonitrile (40.0 g, 115 mmol, 1.00 equivalent), methyl 2-iodobenzoate (45.1 g, 172 mmol, 25.3 mL, 1.50 equivalent), Pd2(dba)3 (5.26 g, 5.74 mmol, 0.050 equivalent), XantPhos (3.32 g, 5.74 mmol, 0.050 equivalent), and cesium carbonate (112 g, 344 mmol, 3.00 equivalent) in 1,4-dioxane (400 mL) was degassed and purged three times with nitrogen. The mixture was then stirred under a nitrogen atmosphere at 100°C for 5 hours. After the reaction was complete, the mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain the residue. The residue was triturated in a mixed solvent of petroleum ether:ethyl acetate:acetonitrile = 3:1:1 (80.0 mL) at 20°C for 10 minutes. The mixture was then filtered, the filtration cake was collected, and dried under reduced pressure to obtain (R)-2-((1-(2-cyano-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-5-yl)ethyl)amino)methyl benzoate (38.0 g, 74.8 mmol, yield 65.2%, purity 95.0%) as a yellow solid. LCMS[M+23] + = 505.2

[0203] 1 H NMR (400MHz, CDCl3) δ=8.38(d,J=6.0Hz,1H), 7.94(dd,J=1.6, 8.0Hz,1H), 7.70(s,1H), 7.69(s,1H), 7.52(d,J=8.8Hz,2H), 7.13-7.04(m,1H), 6.94-6.86 (m,2H), 6.56(t,J=7.2Hz,1H), 6.24(d,J=8.4Hz,1H), 5.68-5.57(m,3H), 3.94(s,3H), 3.79(s,3H), 2.47(s,3H), 1.66(d,J=6.8Hz,3H)

[0204] Step O: To a solution of (R)-2-((1-(2-cyano-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-5-yl)ethyl)amino)methyl benzoate (38.0 g, 74.8 mmol, 1.00 equivalent) in dichloromethane (380 mL), 2,2,2-trifluoroacetic acid (127 g, 1.12 mol, 83.0 mL, 14.9 equivalents) was added at 0°C, and the mixture was stirred at 0°C for 1 hour. The mixture was then slowly poured into saturated sodium bicarbonate (500 mL) at 0°C, and the mixture was extracted with dichloromethane (400 mL x 2). The organic layers were combined, dried on anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by reverse-phase flushing (column: Sfar C18 330 g D Duo 30 μm; mobile phase: phase A: 0.225% formic acid in water, phase B: acetonitrile; gradient: 45%~80% phase B) to obtain (R)-2-((1-(2-cyano-3-hydroxy-7-methylquinoxaline-5-yl)ethyl)amino)methyl benzoate (22.6 g, 60.1 mmol, yield 80.4%, purity 96.4%) as a yellow solid. LCMS[M+1] + =363.0

[0205] 1 H NMR (400MHz, DMSO-d6) δ=12.89(brs,1H), 8.18(brd,J=5.6Hz,1H), 7.81(dd,J=1.6, 8.0Hz,1H), 7.52(s,1H), 7.44(d,J=1.6Hz,1H), 7.24-7.14(m, 1H), 6.56(t,J=7.6Hz,1H), 6.31(d,J=8.4Hz,1H), 5.35(quin,J=6.0Hz,1H), 3.86(s,3H), 2.29(s,3H), 1.46(d,J=6.4Hz,3H) Intermediate B [ka]

[0206] Step A: To a solution of 2-bromo-4-methyl-6-nitroaniline (30.0 g, 130 mmol, 1.00 equivalent) in ethyl acetate (300 mL), tin(II) chloride dihydrate (147 g, 649 mmol, 5.00 equivalent) was added, and the mixture was stirred at 80°C for 3 hours. The reaction mixture was then cooled to 25°C, and the pH of the mixture was adjusted to approximately 8 with sodium bicarbonate (saturated solution in water). The mixture was then filtered, and the filtered cake was washed with ethyl acetate (300 mL x 3). The filtrate was further diluted with water (300 mL), extracted with ethyl acetate (300 mL), the organic layers were combined, washed with brine (500 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The crude product, 3-bromo-5-methylbenzene-1,2-diamine (22.5 g, 112 mmol, 86.2% yield), was obtained as a yellow solid and used without further purification. LCMS[M+H] + =201.1

[0207] Step B: To a solution of 3-bromo-5-methylbenzene-1,2-diamine (22.5 g, 112 mmol, 1.00 equivalent) in ethanol (300 mL), diethyl 2-oxomalonate (23.4 g, 134 mmol, 20.7 mL, 1.20 equivalent) was added, and the mixture was stirred at 80°C for 4 hours. The mixture was then cooled to 25°C, filtered, and the filtered cake was dried under vacuum to obtain ethyl 5-bromo-3-hydroxy-7-methylquinoxaline-2-carboxylate (31.5 g, 92.9 mmol, yield 83.1%) as a yellow solid. LCMS[M+3] + =313.1

[0208] Step C: To a solution of ethyl 5-bromo-3-hydroxy-7-methylquinoxaline-2-carboxylate (31.5 g, 101 mmol, 1.00 equivalent) in methanol (300 mL), ammonium hydroxide (63.4 g, 506 mmol, 69.6 mL, purity 28.0%, 5.00 equivalent) was added, and the mixture was stirred at 25°C for 12 hours. The mixture was then filtered, and the filtered cake was concentrated under reduced pressure to obtain 5-bromo-3-hydroxy-7-methylquinoxaline-2-carboxamide (26.4 g, crude product) as a yellow solid. LCMS[M+3] + =284.0

[0209] Step D: Diisopropylethylamine (2.29 g, 17.7 mmol, 3.09 mL, 5.00 equivalent) was added at 0°C to a solution of 5-bromo-3-hydroxy-7-methylquinoxaline-2-carboxamide (1.00 g, 3.54 mmol, 1.00 equivalent) in POCl3 (10.0 mL), and the mixture was stirred at 120°C for 12 hours. The mixture was then cooled to 25°C, concentrated under vacuum, and the residue was diluted at 0°C with ethyl acetate (50.0 mL x 2). The pH of the mixture was then slowly adjusted to pH=7 using sodium bicarbonate (saturated solution in water), the organic phase was washed with brine (50.0 mL x 2), dried on anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product. The residue was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 50 / 1 to 20 / 1) to obtain 5-bromo-3-chloro-7-methylquinoxaline-2-carbonitrile (1.40 g, 4.86 mmol, yield 68.5%, purity 98.0%) as a yellow solid. LCMS[M+3] + =284.1

[0210] 1 H NMR (400MHz, DMSO-d6) δ=8.37(d,J=1.6Hz,1H), 8.30(d,J=1.6Hz,1H), 8.06(s,1H), 7.96(s,1H), 2.61(s,3H) Intermediate B - Another synthesis [ka]

[0211] Step A: To a mixture of 2-bromo-4-methyl-6-nitroaniline (26.0 g, 113 mmol, 1.00 equivalent) in toluene (250 mL), ethyl 3-chloro-3-oxopropionate (18.6 g, 124 mmol, 15.6 mL, 1.10 equivalent) was added at 0°C. The reaction mixture was then heated to 90°C and stirred for 4 hours. The mixture was then cooled to 25°C, and diisopropyl ether (250 mL) was added, at which point a white precipitate formed. The suspension was filtered, the filter cake was collected, and dried under reduced pressure to obtain ethyl 3-((2-bromo-4-methyl-6-nitrophenyl)amino)-3-oxopropionate (33.0 g, 95.6 mmol, yield 85.0%) as a yellow solid. LCMS[M+3] + =347.2

[0212] 1 H NMR (400MHz, DMSO-d6) δ=10.33(s,1H), 7.93(d,J=1.2Hz,1H), 7.81(d,J=1.2Hz,1H), 4.11(q,J=6.8Hz,2H), 3.46(s,2H), 2.40(s,3H), 1.21(t,J=7.2Hz,3H)

[0213] Step B: To a solution of sodium ethoxide (81.3 g, 239 mmol, 75.0 mL, 20% purity, 2.50 equivalents) in tetrahydrofuran (250 mL) and DMF (250 mL), a solution of ethyl 3-((2-bromo-4-methyl-6-nitrophenyl)amino)-3-oxopropionate (33.0 g, 95.6 mmol, 1.00 equivalent) in a mixed solvent of DMF (50.0 mL) and tetrahydrofuran (50.0 mL) was added at -30°C for 1 hour. The mixture was then heated to 0°C, poured into cold water (80.0 mL), and then 4N HCl (in water, 30.0 mL) was added. The pH of the mixture was adjusted to pH > 7, and the mixture was extracted with ethyl acetate (100 mL x 2). The organic layers were combined, washed with saturated brine (100 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was triturated with diisopropyl ether (35.0 mL) to obtain 5-bromo-2-(ethoxycarbonyl)-3-hydroxy-7-methylquinoxaline 1-oxide (25.0 g, 76.4 mmol, yield 79.9%) as a yellow solid, which was used without further purification. LCMS[M+3] + =329.2

[0214] Step C: To a solution of 5-bromo-2-(ethoxycarbonyl)-3-hydroxy-7-methylquinoxaline 1-oxide (23.0 g, 70.3 mmol, 1.00 equivalent) in DMF (200 mL), PBr3 (38.1 g, 141 mmol, 2.00 equivalent) was added dropwise, and the solution was stirred at 65°C for 1.5 hours. The mixture was then cooled to 25°C, poured into a saturated sodium bicarbonate solution (400 mL), and extracted with ethyl acetate (400 mL x 3). The organic layers were combined, washed with saturated brine (100 mL x 3), dried over sodium sulfate, filtered, and concentrated to obtain the residue. The residue was purified by trituration with n-hexane (300 mL) to obtain ethyl 5-bromo-3-hydroxy-7-methylquinoxaline-2-carboxylate (19.0 g, 61.1 mmol, yield 86.9%) as a yellow solid, which was used without further purification. LCMS[M+H] + =311.0

[0215] 1 H NMR (400MHz, DMSO-d6) δ=12.65-11.74(m,1H), 7.85(s,1H), 7.70(s,1H), 4.39(q,J=7.2Hz,2H), 2.41(s,3H), 1.33(t,J=7.2Hz,3H)

[0216] Step D: To a solution of ethyl 5-bromo-3-hydroxy-7-methylquinoxaline-2-carboxylate (5.70 g, 18.3 mmol, 1.00 equivalent) in tetrahydrofuran (60.0 mL), ammonium hydroxide (6.88 g, 55.0 mmol, 7.56 mL, purity 28%, 3.00 equivalent) was added, and the mixture was stirred at 45°C for 12 hours. After completion, the mixture was cooled to 25°C and concentrated under reduced pressure to obtain 5-bromo-3-hydroxy-7-methylquinoxaline-2-carboxamide (5.10 g, 18.1 mmol, yield 98.7%) as a yellow solid, which was used without further purification. LCMS[M+3] + =283.7

[0217] Step E: To a solution of 5-bromo-3-hydroxy-7-methylquinoxaline-2-carboxamide (4.0 g, 14.2 mmol, 1.00 equivalent) in POCl3 (40.0 mL), diisopropylethylamine (9.16 g, 70.9 mmol, 12.4 mL, 5.0 equivalent) was added at 0°C. The mixture was then heated to 120°C and stirred for 12 hours. The mixture was then cooled to 0°C, diluted with ethyl acetate (150 mL x 2), and the solution was slowly poured into aqueous sodium bicarbonate to adjust the pH to pH > 7. The organic phase was washed with brine (100 mL x 2), dried on anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 5-bromo-3-chloro-7-methylquinoxaline-2-carbonitrile (4.42 g, crude product) as a brown solid, which was used without further purification.

[0218] 1H NMR (400MHz, CDCl3) δ=8.05(d,J=1.6Hz,1H), 7.84(dd,J=0.8, 1.6Hz,1H), 2.56(s,3H) Intermediate C [ka]

[0219] Step A: A mixture of (R)-5-(1-aminoethyl)-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-2-carbonitrile (2.67 g, 7.66 mmol, 1.00 equivalent), methyl 6-chloro-3-fluoropicolinate (2.03 g, 10.7 mmol, 1.40 equivalent), and diisopropylethylamine (4.95 g, 38.3 mmol, 6.67 mL, 5.00 equivalent) in N,N-dimethylformamide (30.0 mL) was subjected to degassing treatment, purged with nitrogen three times, and then stirred under a nitrogen atmosphere at 100°C for 12 hours. After completion, the mixture was cooled to 20°C. The mixture was poured into an aqueous solution (10.0 mL) and extracted with ethyl acetate (30.0 mL x 3). The organic layers were combined, washed with brine (10.0 mL), dried on anhydrous sodium sulfate, and then filtered. The filtrate was concentrated. The residue was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 1 / 0 to 3 / 1) to obtain (R)-6-chloro-3-((1-(2-cyano-3-((4-methoxybenzyl)oxy)-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (2.30 g, 4.00 mmol, yield 52.2%, purity 90%) as a yellow solid. LCMS[M+23] + =540.2

[0220] 1H NMR (400MHz, DMSO-d6) δ=8.40(d,J=7.20Hz,1H), 7.88-7.76(m,2H), 7.52(d,J=8.40Hz,2H), 7.28(d,J=9.20Hz,1H), 7.05(d,J=9.20Hz) ,1H), 6.98(d,J=8.80Hz,2H), 5.74-5.48(m,3H), 3.87(s,3H), 3.76(s,3H), 2.48(s,3H), 1.67(d,J=6.40Hz,3H)

[0221] Step B: To a solution of (R)-6-chloro-3-((1-(2-cyano-3-((4-methoxybenzyl)oxy)-7-methylquinoxalin-5-yl)ethyl)amino) methyl picolinate (1.30 g, 2.51 mmol, 1.00 equivalent) in dichloromethane (10.0 mL), trifluoroacetic acid (4.61 g, 40.4 mmol, 3.00 mL, 16.1 equivalent) was added at 0°C. The mixture was stirred at 25°C for 1 hour. After completion, the mixture was concentrated to obtain (R)-6-chloro-3-((1-(2-cyano-3-hydroxy-7-methylquinoxalin-5-yl)ethyl)amino) methyl picolinate (2.50 g, crude product) as a yellow solid. LCMS[M+1] + =398.2

[0222] Example 1 2-((1-(2-cyano-7-methyl-3-(piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid [ka]

[0223] Step A: To a solution of 5-bromo-3-chloro-7-methylquinoxaline-2-carbonitrile (1.20 g, 4.25 mmol, 1.00 equivalent) in dimethyl sulfoxide (12.0 mL), cesium fluoride (968 mg, 6.37 mmol, 235 μL, 1.50 equivalent) and piperidine (723 mg, 8.49 mmol, 839 μL, 2.00 equivalent) were added. The mixture was stirred at 130°C for 1 hour. After the reaction was complete, the mixture was cooled to 25°C, diluted with water (20.0 mL), and then extracted with ethyl acetate (20.0 mL x 3). The organic layers were combined, dried on anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. The residue was purified by silica gel chromatography (petroleum ether / ethyl acetate 50 / 1~5 / 1) to obtain 5-bromo-7-methyl-3-(piperidine-1-yl)quinoxaline-2-carbonitrile (180 mg, 543 micromoles, yield 12.8%) as a yellow solid. LCMS[M+H] + =331.2

[0224] 1 H NMR (400MHz, DMSO-d6) δ=7.80(d,J=1.6Hz,1H), 7.52(s,1H), 3.70(brd,J=5.2Hz,4H), 2.48(brs,3H), 1.68(brs,6H)

[0225] Step B: A mixture of 5-bromo-7-methyl-3-(piperidine-1-yl)quinoxaline-2-carbonitrile (300 mg, 906 micromoles, 1.00 equivalent), n-butyl vinyl ether (363 mg, 3.62 mmol, 466 μL, 4.00 equivalent), Pd(dppf)Cl2 (66.3 mg, 90.6 micromoles, 0.10 equivalent), and diisopropylethylamine (351 mg, 2.72 mmol, 473 μL, 3.00 equivalent) in n-butyl alcohol (6.00 mL) was degassed, purged three times with nitrogen, and then stirred under a nitrogen atmosphere at 120°C for 8 hours. After the reaction was complete, water (5.00 mL) was added to the mixture and extracted with ethyl acetate (5.00 mL x 3). The organic layers were combined, dried on anhydrous sodium sulfate, and concentrated under vacuum to obtain 5-(1-butoxyvinyl)-7-methyl-3-(piperidine-1-yl)quinoxaline-2-carbonitrile (300 mg, crude product) as a black solid. LCMS[M+H] + =351.2

[0226] Step C: To a solution of 5-(1-butoxyvinyl)-7-methyl-3-(piperidine-1-yl)quinoxaline-2-carbonitrile (300 mg, 856 micromoles, 1.00 equivalent) in tetrahydrofuran (3.00 mL), hydrochloric acid (4.00 M in dioxane, 1.07 mL, 5.00 equivalent) was added. The mixture was stirred at 25°C for 2 hours. Water (20.00 mL) was added to the mixture and extracted with ethyl acetate (20.00 mL x 3). The organic layers were combined, dried on anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by silica gel chromatography (petroleum ether / ethyl acetate 50 / 1~1 / 1) to obtain 5-acetyl-7-methyl-3-(piperidine-1-yl)quinoxaline-2-carbonitrile (140 mg, 441 micromoles, yield 51.7%, purity 92.8%) as a yellow solid. LCMS[M+H] + =294.9

[0227] Step D: To a solution of 5-acetyl-7-methyl-3-(piperidine-1-yl)quinoxaline-2-carbonitrile (80.0 mg, 272 micromoles, 1.00 equivalent) in N,N-dimethylformamide (0.50 mL) under nitrogen, tert-butyl 2-aminobenzoate (63.0 mg, 326 micromoles, 59.0 μL, 1.20 equivalents) and trimethylsilyltrifluoromethanesulfonate (151 mg, 679 micromoles, 123 μL, 2.50 equivalents) were added at 0°C. Next, a solution of borane-tetrahydrofuran complex (1.00 M, 272 μL, 1.00 equivalent) was added. The mixture was stirred at 0°C for 3 hours. The mixture was quenched at 0°C with methanol (3.00 mL). Next, the mixture was diluted with ethyl acetate (5.00 mL), washed with brine (3.00 mL x 3), the organic phase was separated, dried on anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The mixture was purified by preparative TLC (petroleum ether / ethyl acetate 10:1) to obtain tert-butyl 2-((1-(2-cyano-7-methyl-3-(piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoate (40.0 mg, 84.8 micromoles, yield 31.2%) as a yellow solid. LCMS[M+H] + =472.5

[0228] Step E: Trifluoroacetic acid (29.0 mg, 254 micromoles, 18.9 μL, 3.00 equivalents) was added to a solution of 2-((1-(2-cyano-7-methyl-3-(piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoate tert-butyl (40.0 mg, 84.8 micromoles, 1.00 equivalent). The mixture was stirred at 25°C for 2 hours. The reaction product was concentrated under reduced pressure to remove the trifluoroacetic acid, and the residue was neutralized with ammonium hydroxide. The mixture was purified by preparative HPLC (column: YMC-Actus Triart C18 150x30mmx7μm; mobile phase: mobile phase A: 0.225% formic acid in water, mobile phase B: acetonitrile; gradient B%: 80%~100%, 10 minutes) to obtain 2-((1-(2-cyano-7-methyl-3-(piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid (11.2 mg, 26.0 micromoles, yield 30.7%, purity 96.6%) as a yellow solid. LCMS[M+H] + =279.2

[0229] 1 H NMR (400MHz, DMSO-d6) δ=8.47(brd,J=3.2Hz,1H), 7.78(dd,J=1.6, 8.0Hz,1H), 7.63(s,1H), 7.61(d,J=1.6Hz,1H), 7.19-7.13(m,1H), 6.50(t,J=7.6H) z,1H), 6.42(d,J=8.4Hz,1H), 5.51-5.45(m,1H), 3.71(brd,J=6.0Hz,4H), 2.41(s,3H), 1.78-1.67(m,6H), 1.61(d,J=6.8Hz,3H)

[0230] Example 2 2-((1-(2-cyano-3-(isoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid [ka]

[0231] Step A: To a solution of isoindoline (2.80 g, 23.5 mmol, 2.67 mL, 4.74 equivalents) in dimethyl sulfoxide (2.50 mL), 5-bromo-3-chloro-7-methylquinoxaline-2-carbonitrile (1.40 g, 4.96 mmol, 1.00 equivalent) was gradually added. The mixture was stirred at 15°C for 1 hour. After completion, the reaction mixture was poured into water (20.0 mL), during which a yellow precipitate formed. The suspension was filtered, the cake was collected, and dried under reduced pressure to obtain the crude product. The crude product was triturated with a mixed solvent of petroleum ether (3.00 mL) and ethyl acetate (9.00 mL), then filtered, and the cake was collected to obtain 5-bromo-3-(isoindorin-2-yl)-7-methylquinoxaline-2-carbonitrile (1.60 g, 4.38 mmol, yield 88.4%) as a yellow solid, which was used as is. LCMS[M+3] + =367.1

[0232] 1 H NMR (400MHz, CDCl3) δ=7.81(d,J=1.6Hz,1H), 7.59(s,1H), 7.42-7.32(m,2H), 7.31-7.26(m,2H), 7.16-7.01(m,2H), 5.35-5.07(m,4H), 2.42(s,3H)

[0233] Step B: A mixture of 5-bromo-3-(isoindolin-2-yl)-7-methylquinoxaline-2-carbonitrile (1.60 g, 4.38 mmol, 1.00 equivalent), tributyl(1-ethoxyvinyl)tin (2.21 g, 6.12 mmol, 2.07 mL, 1.40 equivalent), and Pd(PPh3)2Cl2 (307 mg, 438 micromoles, 0.10 equivalent) in dioxane (15.0 mL) was stirred under a nitrogen atmosphere at 100 °C for 4 hours. After the reaction was complete, the reaction mixture was cooled to 20 °C, and then KF solution (40 mL) was added at 25 °C and the reaction mixture was quenched by stirring for 1 hour. The solution was extracted with 150 mL (50.0 mL x 3) of ethyl acetate. The organic layers were combined, washed with water (60.0 mL (30.0 mL x 2)), dried, filtered, and concentrated under reduced pressure to obtain 5-(1-ethoxyvinyl)-3-(isoindorin-2-yl)-7-methylquinoxaline-2-carbonitrile (1.50 g, crude product) as a yellow solid. LCMS[M+1] + =357.2

[0234] Step C: To a solution of 5-(1-ethoxyvinyl)-3-(isoindolin-2-yl)-7-methylquinoxaline-2-carbonitrile (1.50 g, 4.21 mmol, 1.00 equivalent) in acetonitrile (20.0 mL), HCl (3 M in water, 1.40 mL, 1.00 equivalent) was added at 10°C. The mixture was stirred at 10°C for 1 hour. After completion, the mixture was slowly adjusted to pH=7 with saturated sodium bicarbonate solution. The suspension was precipitated with ethyl acetate (8.00 mL), the yellow cake was collected by filtration, the solid was washed with ethyl acetate (2.00 mL x 2), and then dried to obtain 5-acetyl-3-(isoindolin-2-yl)-7-methylquinoxaline-2-carbonitrile (1.10 g, 3.35 mmol, yield 79.6%) as a yellow solid, which was used as is. LCMS[M+1] + =329.1

[0235] Step D: Titanium(IV) ethoxide (521 mg, 2.28 mmol, 474 μL, 3.00 equivalent) was added to a solution of 5-acetyl-3-(isoindolin-2-yl)-7-methylquinoxaline-2-carbonitrile (250 mg, 761 micromoles, 1.00 equivalent), 2-methylpropan-2-sulfinamide (185 mg, 1.52 mmol, 2.00 equivalent) in a mixture of tetrahydrofuran (2.10 mL) and 1,2-dimethoxyethane (0.36 mL). The mixture was stirred at 80°C for 16 hours. After completion, the mixture was cooled to 25°C, water (0.50 mL) was added to the reaction product, the suspension was filtered, the solid was washed with ethyl acetate (160 mL (40.0 mL x 4)), the organic solution was combined, washed with brine (15.0 mL (5.0 mL x 3)), dried on anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain N-(1-(2-cyano-3-(isoindolin-2-yl)-7-methylquinoxalin-5-yl)ethylidene)-2-methylpropane-2-sulfinamide (320 mg, crude product) as a yellow solid, which was used as is. LCMS[M+1] + =432.1

[0236] Step E: To a solution of N-(1-(2-cyano-3-(isoindolin-2-yl)-7-methylquinoxalin-5-yl)ethylidene)-2-methylpropane-2-sulfinamide (320 mg, 742 micromoles, 1.00 equivalent) in dichloromethane (3.00 mL), zirconocene hydrochloride (792 mg, 2.97 mmol, 4.00 equivalent) was gradually added at 0°C. The mixture was stirred at 0°C, then heated to 25°C and stirred for 3 hours. After completion, the mixture was quenched with water (2.00 mL) and stirred for 20 minutes. The suspension was filtered and extracted with dichloromethane (30.0 mL x 3). The organic phase was separated, washed with brine (4.00 mL), dried on anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 5 / 1 to 1 / 1) to obtain N-(1-(2-cyano-3-(isoindolin-2-yl)-7-methylquinoxalin-5-yl)ethyl)-2-methylpropane-2-sulfinamide (110 mg, 233 micromoles, yield 31.4%, purity 91.8%) as a yellow solid. LCMS[M+1] + =434.1

[0237] 1 H NMR (400MHz, CDCl3) δ=7.64(s,1H), 7.55(d,J=1.6Hz,1H), 7.49-7.41(m,2H), 7.41-7.34(m,2H), 5.42-5.27(m,4H), 5 .23(quin,J=6.4Hz,1H), 4.54(brd,J=6.0Hz,1H), 2.53(s,3H), 1.72(d,J=6.8Hz,3H), 1.26(s,9H)

[0238] Step F: N-(1-(2-cyano-3-(isoindolin-2-yl)-7-methylquinoxaline-5-yl)ethyl)-2-methylpropane-2-sulfinamide (110 mg, 233 micromoles, 1.00 equivalent) was dissolved in acetonitrile (1.50 mL), to which HCl (4 M in dioxane, 116 μL, 2.00 equivalents) was added. The mixture was stirred at 0°C for 30 minutes. After completion, the reaction mixture was directly concentrated to obtain the crude product. The crude product was triturated with ethyl acetate (1.00 mL) and dried to obtain 5-(1-aminoethyl)-3-(isoindolin-2-yl)-7-methylquinoxaline-2-carbonitrile (80.0 mg, 219 micromoles, yield 93.9%, hydrochloride) as a green solid, which was used as is. LCMS[M+1] + =330.1

[0239] Step G: A mixture of 5-(1-aminoethyl)-3-(isoindolin-2-yl)-7-methylquinoxaline-2-carbonitrilate (80.0 mg, 219 micromoles, 1.00 equivalent, hydrochloride), 2-carboxyphenylboronic acid (109 mg, 656 micromoles, 3.00 equivalent), 1,8-diazabicyclo[5.4.0]undeca-7-ene (166 mg, 1.09 mmol, 165 μL, 5.00 equivalent), copper(II) acetate (59.6 mg, 328 micromoles, 1.50 equivalent), and 4-angstrom molecular sieve (30.0 mg) in dimethylformamide (1.50 mL) was stirred at 25°C for 16 hours. After completion, the mixture was filtered, the filtrate was diluted with water (2.00 mL), ethyl acetate (5.00 mL) was added, and the layers were separated. The aqueous phase was extracted with ethyl acetate (15.0 mL x 3). The extracts were combined, washed with brine (3.00 mL), dried on anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by preparative HPLC (column: Phenomenex Luna C18 150 x 25 mm x 10 μm; mobile phase: Phase A: 0.225% formic acid in water, Phase B: acetonitrile; gradient: 68%~98% Phase B) to obtain 2-((1-(2-cyano-3-(isoindolin-2-yl)-7-methylquinoxalin-5-yl)ethyl)amino)benzoic acid (12.5 mg, 25.5 micromoles, yield 11.7%, purity 91.6%) as a yellow solid. LCMS[M+1] + =450.2

[0240] 1 H NMR (400MHz, DMSO-d6) δ=12.95-12.19(m,1H), 8.69-8.38(m,1H), 7.78(brd,J=7.2Hz,1H), 7.60(s,2H), 7.50(brdd,J=3.2, 5.2Hz,2H), 7.36(brdd,J=3.2, 5.6Hz,2H), 7.18(brt,J=7.6Hz,1H), 6.60-6.44(m,2H), 5.64-5.48(m,1H), 5.36-5.23(m,4H), 2.40(s,3H), 1.68(brd,J=6.8Hz, 3H)

[0241] Examples 3 and 4 (R)-2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid, and (S)-2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid [ka]

[0242] Step A: To a solution of 5-bromo-3-chloro-7-methylquinoxaline-2-carbonitrile (4.42 g, 15.6 mmol, 1.00 equivalent) in dimethyl sulfoxide (30.0 mL), CsF (3.56 g, 23.5 mmol, 866 μL, 1.50 equivalent) and 4,4-difluoropiperidine (3.22 g, 26.6 mmol, 1.70 equivalent) were added. The mixture was stirred at 130°C for 2 hours. After completion, the mixture was cooled to 20°C, and the reaction mixture was slowly added to water (80.0 mL). During this time, a yellow precipitate formed, the suspension was filtered, the cake was collected, and dried under reduced pressure to obtain the crude product. The crude product was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 20 / 1 to 10 / 1) to obtain 5-bromo-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-2-carbonitrile (4.87 g, 13.26 mmol, yield 84.8%) as a yellow solid. LCMS[M+1] + =366.9

[0243] 1 H NMR (400MHz, CDCl3) δ=7.85(d,J=1.6Hz,1H), 7.63(d,J=0.8Hz,1H), 3.98-3.80(m,4H), 2.45(s,3H), 2.26-2.08(m,4H)

[0244] Step B: A mixture of 5-bromo-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-2-carbonitrile (4.80 g, 13.07 mmol, 1 equivalent), tributyl(1-ethoxyvinyl)tin (6.10 g, 16.9 mmol, 5.71 mL, 1.29 equivalents), and Pd(PPh3)2Cl2 (918 mg, 1.31 mmol, 0.10 equivalents) in dioxane (50.0 mL) was stirred under a nitrogen atmosphere at 100°C for 2 hours. After completion, the reaction mixture was heated to 0°C, and then KF solution (100 mL) was added at 25°C and stirred for 1 hour to quench the reaction mixture. The solution was then extracted with ethyl acetate (80.0 mL x 2). The organic layers were combined, washed with water (30.0 mL x 2), dried, filtered, and concentrated under reduced pressure to obtain 3-(4,4-difluoropiperidine-1-yl)-5-(1-ethoxyvinyl)-7-methylquinoxaline-2-carbonitrile (4.68 g, 13.06 mmol, composition) as a white solid, which was used directly in the next step. LCMS[M+1] + =359.1

[0245] Step C: To a solution of 3-(4,4-difluoropiperidine-1-yl)-5-(1-ethoxyvinyl)-7-methylquinoxaline-2-carbonitrile (4.65 g, 13.0 mmol, 1.00 equivalent) in acetonitrile (40.0 mL), HCl (3 M in water, 5.19 mL, 1.20 equivalent) was added at 10°C. The mixture was stirred at 10°C for 1 hour. After completion, the mixture was quenched to pH 7 with saturated sodium bicarbonate solution, and then extracted with ethyl acetate (100 mL x 3). The organic phases were combined, washed with saturated brine (40.0 mL x 2), dried on anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. The crude product was triturated with a mixed solvent of petroleum ether (30.0 mL) and ethyl acetate (10.0 mL) to obtain 5-acetyl-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-2-carbonitrile (3.90 g, 11.8 mmol, yield 91.0%) as a yellow solid, which was then used directly in the next step.

[0246] 1 H NMR (400MHz, CDCl3) δ=7.96(d,J=2.0Hz,1H), 7.84(dd,J=0.8, 2.0Hz,1H), 3.88-3.70(m,4H), 2.80(s,3H), 2.50(s,3H), 2.28-2.10(m,4H)

[0247] Step D: A dry 100 mL three-necked flask containing a magnetic stirring bar was sequentially filled under a nitrogen atmosphere with 5-acetyl-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-2-carbonitrile (500 mg, 1.51 mmol, 1.00 equivalent), tert-butyl 2-aminobenzoate (322 mg, 1.67 mmol, 304 μL, 1.10 equivalent), N,N-dimethylformamide (5.00 mL), and trimethylsilyltrifluoromethanesulfonate (841 mg, 3.78 mmol, 684 μL, 2.50 equivalent). The reaction mixture was cooled to 0°C, and then boranetetrahydrofuran complex (1 M in tetrahydrofuran, 1.82 mL, 1.20 equivalent) was slowly added using a syringe over 10-20 minutes. The reaction mixture was stirred at 0°C for 12 hours. After completion, the mixture was quenched with water (5.0 mL) and stirred for 20 minutes. The solution was extracted with ethyl acetate (20.0 mL) followed by saturated sodium carbonate solution (12.0 mL). The two-phase mixture was stirred until gas generation ceased. The phases were separated, and the aqueous layer was extracted with ethyl acetate (20 mL x 3). The organic layers were combined and dried on anhydrous sodium sulfate, and the solvent was removed under reduced pressure to obtain the residue. The residue was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 1 / 0~10 / 1) to obtain the crude product. The crude product was further purified by preparative TLC (SiO2, petroleum ether / ethyl acetate = 1 / 0~10 / 1) to obtain tert-butyl 2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoate (90.0 mg, 177 micromoles, yield 11.7%) as a yellow solid. LCMS[M+1] + =508.1

[0248] Separation of (R)-2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)tert-butyl benzoate and (S)-2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)tert-butyl benzoate

[0249] 2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxalin-5-yl)ethyl)amino)tert-butyl benzoate (85 mg) was purified by preparative HPLC (column: Daicel Chiralpak IG (250 mm x 50 mm, 10 μm); mobile phase: phase A: CO2, phase B: 0.1% ammonium hydroxide in i-PrOH; phase B%: 10%, isocratic elution mode), and (R)-2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxalin-5-yl)ethyl)amino)tert-butyl benzoate (40.0 mg, 78.8 micromoles, yield 47.1%) (first eluted isomer) was obtained as a yellow oil, and (S)-2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)tert-butyl benzoate (35.0 mg, 69.0 micromoles, yield 41.2%) (second eluted isomer) was obtained as a yellow oil.

[0250] Step E: (R)-2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino) tert-butyl benzoate (40.0 mg, 78.8 micromoles, 1.00 equivalent) was dissolved in dichloromethane (1.00 mL), to which trifluoroacetic acid (0.50 mL) was added. The mixture was stirred at 25°C for 8 hours. After the reaction was complete, the mixture was adjusted to pH=7 with aqueous sodium hydroxide, and then concentrated to obtain the residue. The residue was purified by preparative HPLC (column: Phenomenex Luna C18 150x25mmx10μm; mobile phase: mobile phase A: 0.225% formic acid in water, phase B: acetonitrile; gradient: 60%~90% B) to obtain (R)-2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid (8.10 mg, 17.48 micromoles, yield 22.2%, purity 97.4%) as a yellow solid. LCMS[M+H] + =452.2

[0251] 1 H NMR (400MHz, CD3OD) δ=7.90(d,J=8.0Hz,1H), 7.72-7.62(m,2H), 7.18-7.07(m,1H), 6.52(t,J=7.4Hz,1H), 6.41(d,J=8.4Hz,1 H), 5.60(q,J=6.4Hz,1H), 3.93(brt,J=5.6Hz,4H), 2.47(s,3H), 2.33-2.19(m,4H), 1.69(d,J=6.8Hz,3H)

[0252] Step F: (S)-2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino) tert-butyl benzoate (35.0 mg, 69.0 micromoles, 1.00 equivalent) was dissolved in dichloromethane (1.00 mL), to which trifluoroacetic acid (0.50 mL) was added. The mixture was stirred at 25°C for 8 hours. After the reaction was complete, the mixture was adjusted to pH=7 with sodium hydroxide and then concentrated to obtain the residue. The residue was purified by preparative HPLC (column: Phenomenex Luna C18 150x25mmx10μm; mobile phase: Phase A: 0.225% formic acid in water, Phase B: acetonitrile; gradient: 65%-95% Phase B) to obtain (S)-2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid (15.5 mg, 34.16 micromoles, yield 49.5%, purity 99.5%) as a yellow solid. LCMS[M+H] + =452.3

[0253] 1 H NMR (400MHz, CD3OD) δ=7.79(dd,J=1.4, 7.9Hz,1H), 7.57-7.55(m,2H), 7.08-6.94(m,1H), 6.41(t,J=7.6Hz,1H), 6.30(d,J=8.4 Hz,1H), 5.49(q,J=6.4Hz,1H), 3.81(t,J=5.6Hz,4H), 2.36(s,3H), 2.23-2.08(m,4H), 1.57(d,J=6.8Hz,3H)

[0254] Example 5 (R)-6-chloro-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid [ka]

[0255] Step A: Titanium(IV) ethoxide (3.11 g, 13.6 mmol, 2.82 mL, 3.00 equivalent) was added to a solution of 5-acetyl-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-2-carbonitrile (1.50 g, 4.54 mmol, 1.00 equivalent) and (R)-2-methylpropane-2-sulfinamide (1.10 g, 9.08 mmol, 2.00 equivalent) in a mixture of tetrahydrofuran (15.0 mL) and 1,2-dimethoxyethane (3.00 mL). The mixture was stirred at 75°C for 16 hours. After the reaction was complete, the mixture was cooled to 25°C, water (2.00 mL) was added to the reaction mixture, and the mixture was stirred at 25°C for 0.5 hours. The reaction mixture was filtered, the filtered cake was washed with ethyl acetate (50.0 mL x 4), the organic layers were combined and washed with brine (60.0 mL (20.0 mL x 3)), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain (R)-N-(1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethylidene)-2-methylpropane-2-sulfinamide (1.80 g, 4.15 mmol, yield 91.4%) as a yellow oil, which was used as is.

[0256] Step B: Zirconocene hydrochloride (2.94 g, 11.0 mmol, 4.0 equivalents) was gradually added to a solution of (R)-N-(1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethylidene)-2-methylpropane-2-sulfinamide in dichloromethane (30.0 mL). The mixture was stirred at 25°C for 12 hours. After completion, the mixture was quenched with water (10 mL) and stirred for 20 minutes. Next, the suspension was filtered and diluted with dichloromethane (30.0 mL x 3). The organic phase was separated, washed with brine (20.0 mL), dried on anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 10 / 1 to 1 / 1) to obtain (R)-N-((R)-1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)-2-methylpropane-2-sulfinamide (1.24 g, 2.57 mmol, yield 67.6%, purity 90.3%) as a yellow solid. LCMS[M+1] + =436.1

[0257] 1 H NMR (400MHz, CDCl3) δ=7.62(d,J=0.8Hz,1H), 7.53(d,J=1.6Hz,1H), 5.13(quin,J=6.8Hz,1H), 4.21(brd,J=6.8Hz,1H) , 3.77(brt,J=5.6Hz,4H), 2.47(s,3H), 2.30-2.09(m,4H), 1.57(d,J=6.8Hz,3H), 1.23-1.10(m,9H)

[0258] Step C: (R)-N-((R)-1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)-2-methylpropane-2-sulfinamide (330 mg, 722.84 micromoles, 1.00 equivalent) was dissolved in acetonitrile (3.00 mL), to which HCl (4 M in dioxane, 361.42 μL, 2.00 equivalents) was added dropwise at 0°C. The mixture was stirred at 0°C for 1 hour. The reaction mixture was concentrated directly to obtain the crude product. The crude product was triturated with ethyl acetate (1.00 mL), the cake was collected and dried to obtain (R)-5-(1-aminoethyl)-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-2-carbonitrile (205 mg, 557.33 micromoles, yield 77.1%, hydrochloride) as a yellow solid. LCMS[M+1] + =332.1

[0259] Step D: A mixture of (R)-5-(1-aminoethyl)-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-2-carbonitride (195 mg, 530 micromoles, 1.00 equivalent, hydrochloride), 6-chloro-3-fluoropyridine-2-carboxylate methyl (241 mg, 1.27 mmol, 2.40 equivalents), and diisopropylethylamine (480 mg, 3.71 mmol, 646 μL, 7.00 equivalents) in dimethylformamide (1.50 mL) was stirred at 80°C for 9 hours. After completion, the mixture was cooled to 25°C, the reaction mixture was diluted with water (20.0 mL), and extracted with ethyl acetate (40.0 mL x 2). The organic layers were combined, washed with a saturated sodium bicarbonate solution (20.0 mL), dried on anhydrous sodium sulfate, and concentrated under reduced pressure to obtain (R)-6-chloro-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (280 mg, 430 micromoles, yield 81.2%, purity 77%) as a yellow oil, which was used as is. LCMS[M+1] + =501.2

[0260] Step E: A mixture of (R)-6-chloro-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (90.0 mg, 138 micromoles, 1.00 equivalent) and lithium chloride (58.7 mg, 1.38 mmol, 28.4 μL, 10.0 equivalents) in dimethyl sulfoxide (0.50 mL) was stirred at 130°C for 3 hours. After completion, the mixture was cooled to 25°C and the reaction mixture was filtered. The filtrate was purified by preparative HPLC (column: YMC-Actus Triart C18 150x30mmx7μm; mobile phase: phase A: 0.225% formic acid in water, phase B: acetonitrile; gradient 63%~93% phase B) to obtain (R)-6-chloro-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid (22.2 mg, 45.2 micromoles, yield 32.7%, purity 99.2%) as a yellow solid. LCMS[M+23] + =509.1

[0261] 1 H NMR (400MHz, CDCl3) δ=11.07-10.33(m,1H), 8.38(brd,J=6.4Hz,1H), 7.70(s,1H), 7.58(d,J=1.6Hz,1H), 7.13(d,J=8.8Hz,1H), 6.77(d ,J=8.8Hz,1H), 5.51(quin,J=6.4Hz,1H), 3.99-3.83(m,4H), 2.50(s,3H), 2.39-2.17(m,4H), 1.73(d,J=6.8Hz,3H)

[0262] Example 6 (R)-2-((1-(2-cyano-3-(isoindolin-2-yl)-7-methylquinoxalin-5-yl)ethyl)amino)benzoic acid [ka]

[0263] Step A: Tetraethoxytitanium (1.04 g, 4.57 mmol, 947 μL, 3.00 equivalent) was added to a solution of 5-acetyl-3-(isoindolin-2-yl)-7-methylquinoxaline-2-carbonitrile (500 mg, 1.52 mmol, 1.00 equivalent) and (R)-2-methylpropane-2-sulfinamide (369 mg, 3.05 mmol, 2.00 equivalent) in a mixture of tetrahydrofuran (4.20 mL) and 1,2-dimethoxyethane (0.72 mL). The mixture was stirred at 80°C for 16 hours. After completion, the mixture was cooled to 25°C, the reaction mixture was quenched with water (0.50 mL), the suspension was filtered, the cake was washed with ethyl acetate (20.0 mL x 4), the organic layers were combined and washed with brine (2.00 mL x 3), dried on anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain (R)-N-(1-(2-cyano-3-(isoindolin-2-yl)-7-methylquinoxalin-5-yl)ethylidene)-2-methylpropane-2-sulfinamide (680 mg, crude product) as a yellow solid, which was used as is. LCMS[M+1] + =432.2

[0264] Step B: To a solution of (R)-N-(1-(2-cyano-3-(isoindolin-2-yl)-7-methylquinoxalin-5-yl)ethylidene)-2-methylpropane-2-sulfinamide (600 mg, 1.39 mmol, 1.00 equivalent) in dichloromethane (9.00 mL), zirconocene hydrochloride (1.48 g, 5.56 mmol, 4.00 equivalent) was gradually added at 0°C. The mixture was stirred at 0°C, then heated to 25°C and stirred for 3 hours. After completion, the mixture was quenched with water (5 mL) and stirred for 20 minutes. The suspension was filtered and extracted with dichloromethane (30.0 mL x 3). The organic phase was separated, washed with brine (10.0 mL), dried on anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 5 / 1 to 1 / 1) to obtain (R)-N-((R)-1-(2-cyano-3-(isoindolin-2-yl)-7-methylquinoxalin-5-yl)ethyl)-2-methylpropane-2-sulfinamide (286 mg, 641 micromoles, yield 46.1%, purity 97.2%) as a yellow solid.

[0265] 1 H NMR (400MHz, CDCl3) δ=7.66(s,1H), 7.57(d,J=1.6Hz,1H), 7.51-7.43(m,2H), 7.43-7.37(m,2H), 5.43-5.29(m,4H), 5.24(quin ,J=6.4Hz,1H), 4.56(brd,J=6.4Hz,1H), 2.67-2.50(m,1H), 2.54(s,2H), 1.73(d,J=6.8Hz,3H), 1.28(s,9H)

[0266] Step C: To a solution of (R)-N-((R)-1-(2-cyano-3-(isoindolin-2-yl)-7-methylquinoxaline-5-yl)ethyl)-2-methylpropane-2-sulfinamide (130 mg, 291 micromoles, 1.00 equivalent) in acetonitrile (1.50 mL), HCl (4 M in dioxane, 146 μL, 2.00 equivalents) was added at 0°C, and the mixture was stirred at 0°C for 1 hour. After completion, the reaction mixture was directly concentrated to obtain the crude product. The crude product was triturated with ethyl acetate (1.00 mL) and dried to obtain (R)-5-(1-aminoethyl)-3-(isoindolin-2-yl)-7-methylquinoxaline-2-carbonitrile (70.0 mg, 191 micromoles, yield 65.7%, hydrochloride) as a yellow solid. LCMS[M+1] + =330.2

[0267] Step D: A mixture of (R)-5-(1-aminoethyl)-3-(isoindolin-2-yl)-7-methylquinoxaline-2-carbonitrilate (70.0 mg, 191 micromoles, 1.00 equivalent, hydrochloride), 2-carboxyphenylboronic acid (95.3 mg, 574 micromoles, 3.00 equivalent), 1,8-diazabicyclo[5.4.0]undeca-7-ene (146 mg, 957 micromoles, 144 μL, 5.00 equivalent), copper(II) acetate (52.1 mg, 287 micromoles, 1.50 equivalent), and 4-angstrom molecular sieve (50.0 mg, 13.7 micromoles) in N,N-dimethylformamide (1.00 mL) was stirred at 25°C for 16 hours. After completion, the mixture was filtered and the filtrate was diluted with water (2.00 mL). Next, ethyl acetate (5.00 mL) was added and the layers were separated. The aqueous phase was extracted with ethyl acetate (15.0 mL x 3). The organic layers were combined, washed with brine (3.00 mL), dried on anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by preparative HPLC (column: Phenomenex Luna C18 150x25 mm x 10 μm; mobile phase: phase A: 0.225% formic acid in water, phase B: acetonitrile; gradient: 68%-98% phase B) to obtain (R)-2-((1-(2-cyano-3-(isoindolin-2-yl)-7-methylquinoxalin-5-yl)ethyl)amino)benzoic acid (17.0 mg, 37.7 micromoles, yield 19.7%, purity 99.6%) as a yellow solid. LCMS[M+1] + =450.2

[0268] 1 H NMR (400MHz, CDCl3) δ=8.45-8.11(m,1H), 7.99(dd,J=1.2, 8.0Hz,1H), 7.61(d,J=8.0Hz,2H), 7.50-7.41(m,2H), 7.40-7.34(m,2H), 7.25-7.1 2(m,1H), 6.59(t,J=7.2Hz,1H), 6.43(d,J=8.4Hz,1H), 5.72-5.54(m,1H), 5.36(s,4H), 2.46(s,3H), 1.76(d,J=6.8Hz,3H)

[0269] Example 7 6-Chloro-3-(((1R)-1-(2-Cyano-3-(6,6-Difluoro-3-azabicyclo[3.1.1]heptan-3-yl)-7-Methylquinoxaline-5-yl)ethyl)amino)picolinic acid [ka]

[0270] Step A: To a solution of (R)-6-chloro-3-((1-(2-cyano-3-hydroxy-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (100 mg, 251 micromoles, 1.00 equivalent) in dimethyl sulfoxide (1.00 mL), benzotriazole-1-yloxytris-pyrrolidine o-phosphonium hexafluorophosphate (196 mg, 377 micromoles, 1.50 equivalents), 6,6-difluoro-3-azabicyclo[3.1.1]heptane hydrochloride (77.7 mg, 377 micromoles, 1.50 equivalents) and diisopropylethylamine (162 mg, 1.26 mmol, 219 μL, 5.00 equivalents) were added. The mixture was stirred at 20°C for 1 hour. After completion, the mixture was poured into a saturated aqueous solution (1.00 mL) and extracted with ethyl acetate (3 x 5.00 mL). The organic solutions were combined, washed with brine (1.00 mL), and the organic layer was collected and concentrated to obtain the residue. The residue was purified by preparative TLC (SiO2, petroleum ether / ethyl acetate = 3 / 1) to obtain 6-chloro-3-(((1R)-1-(2-cyano-3-(6,6-difluoro-3-azabicyclo[3.1.1]heptan-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (50.0 mg, 87.7 micromoles, yield 34.9%, purity 75%) as a white solid. LCMS[M+1] + = 513.3

[0271] Step B: 6-chloro-3-(((1R)-1-(2-cyano-3-(6,6-difluoro-3-azabicyclo[3.1.1]heptan-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinate methyl (40.0 mg, 82.9 micromoles, 1.00 equivalent) was dissolved in dimethyl sulfoxide (0.50 mL), to which lithium chloride (35.1 mg, 829 micromoles, 10.0 equivalents) was added. The reaction mixture was stirred at 170°C for 1 hour. After completion, the mixture was cooled to 20°C. The mixture was filtered. The filtrate was purified by preparative HPLC (column: Waters Xbridge 150x25mmx5μm; mobile phase: Phase A: water (10 mmol / L NH4HCO3), Phase B: acetonitrile; gradient: 10%~40% Phase B), and then further purified by preparative HPLC (column: Phenomenex Luna C18 150x25mmx10μm; mobile phase: Phase A: 0.225% formic acid in water, Phase B: acetonitrile; gradient: 15%-45%). Purified by exposure to phase B), 6-chloro-3-(((1R)-1-(2-cyano-3-(6,6-difluoro-3-azabicyclo[3.1.1]heptan-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid (5.36 mg, 11.0 micromoles, yield 13.3%, purity 96.1%) was obtained as a yellow solid. LCMS[M+23] + = 521.3

[0272] 1 1H NMR (400MHz, DMSO-d6) δ=8.66-8.31(m,1H), 7.63(t,J=6.40Hz,2H), 7.29(d,J=8.80Hz,1H), 7.17 -6.91(m,1H), 5.54-5.37(m,1H), 4.53(brdd,J=4.00, 12.4Hz,1H), 4.36-4. 20(m,1H), 3.80-3.64(m,2H), 3.63-3.50(m,1H), 3.12-2.98(m,1H), 2.96- 2.78(m,1H), 2.52(brs,1H), 2.41(d,J=2.00Hz,3H), 1.66(t,J=7.20Hz,3H)

[0273] 19F NMR (400MHz, DMSO-d6) δ=-92.47, -93.84, -94.83

[0274] Examples 8 and 9 6-Chloro-3-(((R)-1-(2-cyano-3-((1S,4S)-5,5-difluoro-2-azabicyclo[2.2.1]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid (Example 8) and 6-Chloro-3-(((R)-1-(2-cyano-3-((1R,4R)-5,5-difluoro-2-azabicyclo[2.2.1]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid (Example 9) [ka]

[0275] Step A: Diisopropylethylamine (244 mg, 1.89 mmol, 328 μL, 5.00 equivalent) and benzotriazole-1-yloxytris-pyrrolidine o-phosphonium hexafluorophosphate (294 mg, 565 micromol, 1.50 equivalent) were added to a solution of (R)-6-chloro-3-((1-(2-cyano-3-hydroxy-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (150 mg, 377 micromoles, 1.00 equivalent) in N,N-dimethylformamide (1.50 mL). The reaction mixture was stirred at 20°C for 15 minutes. Next, 5,5-difluoro-2-azabicyclo[2.2.1]heptane hydrochloride (95.9 mg, 565 micromoles, 1.50 equivalents) was added to the above mixture, and the mixture was stirred at 20°C for 1 hour. After completion, the reaction mixture was diluted with water (5.00 mL) and extracted with ethyl acetate (3 x 5.00 mL). The organic layers were combined and concentrated to obtain a residue. The residue was purified by preparative TLC (petroleum ether:ethyl acetate = 3 / 1) to obtain 6-chloro-3-(((1R)-1-(2-cyano-3-(5,5-difluoro-2-azabicyclo[2.2.1]heptane-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinate methyl (180 mg, 316 micromoles, yield 83.8%, purity 90%) as a yellow solid. LCMS[M+1] + =513.1

[0276] Step B: A mixture of 6-chloro-3-(((1R)-1-(2-cyano-3-(5,5-difluoro-2-azabicyclo[2.2.1]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (180 mg, 316 micromoles, 1.00 equivalent) was purified by supercritical fluid chromatography (SFC) (column: Daicel ChiralCel OX (250 mm x 30 mm, 10 μm); mobile phase: phase A: CO2, phase B: 0.1% ammonium hydroxide in MeOH; 40% phase B isocratic elution). The desired fraction of the first peak was collected and concentrated to obtain the methyl ester of Example 8 (30.0 mg, 42.7 micromoles, yield 12.2%, purity 73%) as a yellow solid (first eluting isomer). LCMS[M+1] + =513.2; The desired fraction of the second peak was collected and concentrated to obtain the methyl ester of Example 9 (30.0 mg, 40.4 micromoles, yield 11.5%, purity 69%) as a yellow solid (second eluting isomer). LCMS[M+1] + = 513.2

[0277] Saponification of methyl esters in Examples 8 and 9

[0278] To a solution of methyl ester (25.0 mg, 48.7 micromoles, 1.00 equivalent) from Example 8 in dimethyl sulfoxide (0.50 mL), lithium chloride (20.7 mg, 487 micromoles, 10.0 equivalents) was added. The mixture was stirred at 130°C for 4 hours. After completion, the mixture was cooled to 20°C and filtered. The filtrate was purified by preparative HPLC (column: Welch Xtimate C18 150*25 mm*5 μm; mobile phase: phase A: 0.225% formic acid in water, phase B: acetonitrile; gradient: 55%-85% phase B) to obtain Example 8 (9.45 mg, 18.7 micromoles, yield 38.3%, purity 98.5%) as a yellow solid. LCMS[M+23] + = 521.2

[0279] 11H NMR (400MHz, CDCl3-d) δ=10.71(s,1H), 8.37(brd,J=6.0Hz,1H), 7.61(s,1H), 7.49(d,J=1.2Hz, 1H), 7.13(d,J=8.8Hz,1H), 6.78(d,J=8.8Hz,1H), 5.44-5.34(m,1H), 5.1 0(brs,1H), 4.14-4.05(m,1H), 3.92(d,J=10.4Hz,1H), 3.11-3.02(m,1H) , 2.44(s,3H), 2.41-2.27(m,2H), 2.20-2.07(m,2H), 1.70(d,J=6.8Hz,3H)

[0280] 19 F NMR (400MHz, CDCl3-d) δ=-89.30, -89.91, -108.36, -108.96

[0281] To a solution of methyl ester (30.0 mg, 58.5 micromoles, 1.00 equivalent) from Example 9 in dimethyl sulfoxide (0.50 mL), lithium chloride (24.8 mg, 585 micromoles, 10.0 equivalents) was added. The reaction mixture was stirred at 130°C for 4 hours. After completion, the mixture was cooled to 20°C and filtered. The filtrate was purified by preparative HPLC (column: Welch Xtimate C18 150x25mmx5μm; mobile phase: phase A: 0.225% formic acid in water, phase B: acetonitrile, gradient: 55%~85% phase B) to obtain Example 9 (6.22 mg, 12.3 micromoles, yield 21.0%, purity 98.6%) as a yellow solid. LCMS[M+23] + = 521.2

[0282] 1H NMR (400MHz, CDCl3-d) δ=8.40-8.31(d,J=5.6Hz,1H), 7.61(s,1H), 7.50(s,1H), 7.10(d,J=8.8Hz,1H), 6.71(d,J=8.8Hz,1H), 5.47-5.37(m,1H), 5.06(brs,1H) , 4.15-4.07(m,1H), 3.91(d,J=10.4Hz,1H), 3.11-3.03(m,1H), 2.44(s,3H), 2.41-2.27(m,2H), 2.20-2.07(m,2H), 1.69(d,J=6.8Hz,3H)

[0283] 19 F NMR (400MHz, CDCl3-d) δ=-89.32, -89.92, -108.53, -109.13

[0284] Examples 10 and 11 6-Chloro-3-(((R)-1-(2-cyano-3-((1R,4S)-6,6-difluoro-2-azabicyclo[2.2.1]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid (Example 11) and 6-Chloro-3-(((R)-1-(2-cyano-3-((1S,4R)-6,6-difluoro-2-azabicyclo[2.2.1]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid (Example 10) [ka]

[0285] Step A: To a solution of (R)-6-chloro-3-((1-(2-cyano-3-hydroxy-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (200 mg, 502 micromoles, 1.00 equivalent) in N,N-dimethylformamide (4.00 mL), benzotriazole-1-yloxytris-pyrrolidine o-phosphonium hexafluorophosphate (392 mg, 754 micromoles, 1.50 equivalent) and diisopropylethylamine (162 mg, 1.26 mmol, 219 μL, 5.00 equivalent) were added. The reaction mixture was stirred at 25°C for 30 minutes. Next, 6,6-difluoro-2-azabicyclo[2.2.1]heptane hydrochloride (128 mg, 754 micromoles, 1.50 equivalents) was added to the above mixture at 25°C, and the reaction was stirred at 25°C for 48 hours. After completion, the mixture was diluted with water (10.0 mL) and extracted with ethyl acetate (3 x 20.0 mL). The organic layers were combined, washed with brine (3 x 10.0 mL), dried on anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by preparative TLC (SiO2, petroleum ether:ethyl acetate = 2:1) to obtain 6-chloro-3-(((1R)-1-(2-cyano-3-(6,6-difluoro-2-azabicyclo[2.2.1]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinate methyl (90.0 mg, 175 micromoles, yield 34.9%) as a yellow solid.

[0286] Step B: 6-chloro-3-(((1R)-1-(2-cyano-3-(6,6-difluoro-2-azabicyclo[2.2.1]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinate (90.0 mg, 175 micromoles) was purified by SFC (column: Daicel ChiralCell OX (250 mm x 30 mm, 10 μm); mobile phase: phase A: CO2, phase B: ammonium hydroxide in MeOH; phase B%: 40%, isocratic elution mode) to obtain the methyl ester of Example 10 (25 mg, 48.7 micromoles, yield 27.8%) as a yellow solid (first eluted isomer), and the methyl ester of Example 11 (40.0 mg, 78.0 micromoles, yield 44.4%) was isolated as the second eluted isomer as a yellow solid.

[0287] Saponification of methyl esters in Examples 10 and 11

[0288] Lithium chloride (10.3 mg, 244 micromoles, 5.00 equivalents) was added to a solution of methyl ester (25.0 mg, 48.7 micromoles, 1.00 equivalent) of Example 10 in dimethyl sulfoxide (0.20 mL). The reaction mixture was stirred at 130°C for 1 hour. After completion, the mixture was cooled to 20°C and purified by preparative HPLC (column: Waters X-Bridge 150x25 mmx5 μm; mobile phase: phase A: water (10 mmol / L NH4HCO3), phase B: acetonitrile; gradient: 22%-52% phase B) to obtain Example 10 (9.22 mg, 17.9 micromoles, yield 36.6%, purity 96.6%) as a yellow solid. LCMS[M+23] + = 521.2

[0289] 1H NMR (400MHz, DMSO-d6) δ=9.24(brs,1H), 7.61(s,1H), 7.58(s,1H), 7.06(brd,J=8.4Hz,1H), 6.84(brd,J=6.8Hz,1H), 5.39(s,2H), 4.01-3.93 (m,1H), 3.75(d,J=9.6Hz,1H), 2.90(brs,1H), 2.40(s,3H), 2.30-2.17(m,1H), 2.12-1.90(m,3H), 1.61(d,J=6.4Hz,3H)

[0290] 19 F NMR (377MHz, DMSO-d6) δ=-89.18, -89.76, -110.69, -111.27

[0291] Step D: Lithium chloride (16.5 mg, 390 micromoles, 5.00 equivalents) was added to a solution of methyl ester (40.0 mg, 78.0 micromoles, 1.00 equivalent) of Example 11 in dimethyl sulfoxide (0.40 mL). The reaction mixture was stirred at 130°C for 1 hour. After completion, the mixture was cooled to 20°C and purified by preparative HPLC (column: Waters X-Bridge 150x25 mmx5 μm; mobile phase: phase A: water (10 mmol / L NH4HCO3), phase B: acetonitrile; gradient: 22%-52% phase B) to obtain Example 11 (7.38 mg, 14.51 micromoles, yield 18.6%, purity 98.1%) as a yellow solid. LCMS[M+23] + = 521.2

[0292] 1 H NMR (400MHz, DMSO-d6) δ=9.20(brs,1H), 7.57(s,1H), 7.51(d,J=1.6Hz,1H), 7.08(d,J=8.8Hz,1H), 6.71(brd,J=8.8Hz,1H), 5.39(brd,J=6.4Hz,1H), 5.33(s,1H) ), 4.00(brd,J=8.0Hz,1H), 3.68(d,J=9.6Hz,1H), 2.89(brs,1H), 2.37(s,3H), 2.30-2.16(m,1H), 2.11-1.88(m,3H), 1.58(d,J=6.8Hz,3H)

[0293] 19 F NMR (400MHz, DMSO-d6) δ=-89.67, -90.26, -110.71, -111.28

[0294] Example 12 (R)-6-chloro-3-((1-(2-cyano-3-(3,3-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid [ka]

[0295] Step A: To a solution of (R)-6-chloro-3-((1-(2-cyano-3-hydroxy-7-methylquinoxaline-5-yl)ethyl)amino) methyl picolinate (90.0 mg, 226 micromoles, 1.00 equivalent) in N,N-dimethylformamide (0.20 mL), benzotriazole-1-yloxytris-pyrrolidine o-phosphonium hexafluorophosphate (177 mg, 339 micromoles, 1.50 equivalents) and diisopropylethylamine (146 mg, 1.213 mmol, 197 μL, 5.00 equivalents) were added. The reaction mixture was stirred at 25°C for 30 minutes. Next, 3,3-difluoropiperidine hydrochloride (41.1 mg, 261 micromoles, 1.15 equivalents) was added to the above mixture at 25°C. The reaction mixture was stirred at 25°C for 11.5 hours. After completion, the mixture was diluted with water (10.0 mL) and extracted with ethyl acetate (10.0 mL x 3). The organic solutions were combined, washed with brine (10.0 mL x 3), dried on anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by preparative TLC (SiO2, petroleum ether:ethyl acetate = 2:1) to obtain (R)-6-chloro-3-((1-(2-cyano-3-(3,3-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (30.0 mg, 46.1 micromoles, yield 20.4%) as a yellow solid. LCMS[M+1] + =501.1

[0296] Step B: Lithium chloride (8.46 mg, 200 micromoles, 5.00 equivalents) was added to a solution of (R)-6-chloro-3-((1-(2-cyano-3-(3,3-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (20.0 mg, 39.9 micromoles, 1.00 equivalent) in dimethyl sulfoxide (0.20 mL). The reaction mixture was stirred at 130 °C for 5 hours. After completion, the mixture was cooled to 20°C and purified by preparative HPLC (column: Phenomenex Luna C18 150x25mmx10μm; mobile phase: phase A: water (10 mmol / L NH4HCO3), phase B: acetonitrile; gradient: 26%-56% phase B) to obtain (R)-6-chloro-3-((1-(2-cyano-3-(3,3-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid (12.7 mg, 25.5 micromoles, yield 63.8%, purity 97.3%) as a yellow solid. LCMS[M+23] + = 509.2

[0297] 1 H NMR (400MHz, DMSO-d6) δ=9.38(brs,1H), 7.68(s,1H), 7.64(s,1H), 7.03(brd,J=8.8Hz,1H), 6.75(brd,J=8.0Hz,1H), 5.53-5.35(m,1H), 4. 15-3.90(m,2H), 3.86-3.64(m,2H), 2.44-2.39(s,3H), 2.22-2.09(m,2H), 2.01-1.84(m,2H), 1.59(brd,J=6.8Hz,3H)

[0298] 19 F NMR (400MHz, DMSO-d6) δ=-99.17, -99.22.

[0299] Examples 13 and 14 6-Chloro-3-(((R)-1-(2-cyano-3-((((S)-2,2-difluorocyclopropyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid (Example 13) and 6-Chloro-3-(((R)-1-(2-cyano-3-((((R)-2,2-difluorocyclopropyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid (Example 14) [ka]

[0300] Step A: To a solution of (R)-6-chloro-3-((1-(2-cyano-3-hydroxy-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (200 mg, 503 micromoles, 1.00 equivalent) in N,N-dimethylformamide (2.00 mL), benzotriazole-1-yloxytris-pyrrolidine o-phosphonium hexafluorophosphate (392 mg, 754 micromoles, 1.50 equivalent) and diisopropylethylamine (325 mg, 2.51 mmol, 438 μL, 5.00 equivalent) were added. The reaction mixture was stirred at 15°C for 20 minutes. To the above mixture, (2,2-difluorocyclopropyl)methaneamine hydrochloride (108 mg, 75 micromoles, 1.50 equivalent) was added. The reaction mixture was stirred at 15°C for 1 hour. After completion, the mixture was diluted with water (10.0 mL) and extracted with ethyl acetate (10.0 mL x 3). The organic solutions were combined, washed with brine (30.0 mL), dried on anhydrous sodium sulfate, filtered, and concentrated to obtain the residue. The residue was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 1 / 0~5 / 1) and preparative HPLC (column: Phenomenex Luna C18 150x25mmx10μm; mobile phase: phase A: water (10 mmol / L NH4HCO3), phase B: acetonitrile; gradient: 64%~94% phase B over 10 minutes) to obtain 6-chloro-3-(((1R)-1-(2-cyano-3-(((2,2-difluorocyclopropyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (30.0 mg, 61.6 micromoles, yield 12.3%) as a yellow solid. LCMS[M+1] + =487.2

[0301] Step B: A mixture of 6-chloro-3-(((1R)-1-(2-cyano-3-(((2,2-difluorocyclopropyl)methyl)amino)-7-methylquinoxaline-5-ylethyl)amino)methyl picolinate (30.0 mg, 61.6 micromoles, 1.00 equivalents) was purified by SFC (column: Daicel Chiralpak AD (250 mm x 50 mm, 10 μm); mobile phase: phase A: hexane, phase B: 0.1% ammonia in isopropanol; phase B%: 12%, isocratic elution). The desired fraction was collected and concentrated to obtain the methyl ester of Example 13 (11.0 mg, 22.4 micromoles, yield 36.3%, purity 99.0%) as a yellow solid (first eluting isomer; LCMS[M+1]). + =487.3) was obtained as the methyl ester of Example 14 (11.0 mg, 21.9 micromoles, yield 35.6%, purity 97.1%), which was then converted into a yellow solid (the next isomer to elute, LCMS[M+1] + It was isolated as (=487.3).

[0302] Saponification of methyl esters in Examples 13 and 14

[0303] To a solution of methyl ester (10.0 mg, 20.5 micromoles, 1.00 equivalent) from Example 13 in dimethyl sulfoxide (0.50 mL), lithium chloride (8.71 mg, 205 micromoles, 10.0 equivalents) was added. The reaction mixture was stirred at 130°C for 5 hours. After completion, the mixture was cooled to 20°C. The mixture was filtered, and the filtrate was purified by preparative HPLC (column: Phenomenex Luna C18 150x25 mmx10 μm; mobile phase: phase A: water (10 mmol / L NH4HCO3), phase B: acetonitrile; gradient: 22% to 52% phase B over 10 minutes) to obtain Example 13 (4.12 mg, 8.60 micromoles, yield 41.9%, purity 98.7%) as a yellow solid. LCMS[M-1] - =471.2

[0304] 1H NMR (400MHz, DMSO-d6) δ=9.25(brs,1H), 8.00(t,J=5.6Hz,1H), 7.55(s,2H), 7.06(brd,J=8.4Hz,1H), 6.73(brd,J=7.2Hz,1H), 5.49-5.35(m,1H), 3.8 2-3.70(m,1H), 3.54-3.44(m,1H), 2.37(s,3H), 2.27-2.13(m,1H), 1.67-1.60(m,1H), 1.56(d,J=6.8Hz,3H), 1.48-1.35(m,1H)

[0305] 19 F NMR (400MHz, DMSO-d6) δ=-126.46, -126.87, -141.37, -141.79

[0306] To a solution of methyl ester (10.0 mg, 20.5 micromoles, 1.00 equivalent) of Example 14 in dimethyl sulfoxide (0.50 mL), lithium chloride (8.71 mg, 205 micromoles, 10.0 equivalents) was added. The reaction mixture was stirred at 130°C for 5 hours. After completion, the mixture was cooled to 20°C. The mixture was filtered, and the filtrate was purified by preparative HPLC (column: Phenomenex Luna C18 150x25 mmx10 μm; mobile phase: phase A: water (10 mmol / L NH4HCO3), phase B: acetonitrile; gradient: 24% to 54% phase B over 10 minutes) to obtain Example 14 (5.15 mg, 10.8 micromoles, yield 52.5%, purity 99.0%) as a yellow solid. LCMS[M-1] - =471.2

[0307] 1H NMR (400MHz, DMSO-d6) δ=9.25(brs,1H), 8.00(t,J=5.6Hz,1H), 7.56(s,2H), 7.05(brd,J=8.8Hz,1H), 6.71(brd,J=8.4Hz,1H), 5.49-5.37(m,1H), 3.71(m,1H), 3.54-3.47(m,1H), 2.37(s,3H), 2.28-2.14(m,1H), 1.64-1.58(m,1H), 1.56(d,J=6.8Hz,3H), 1.46-1.33(m,1H)

[0308] 19 F NMR (400MHz, DMSO-d6) δ=-126.40, -126.81, -141.44, -141.52

[0309] Example 15 (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)quinoxaline-5-yl)ethyl)amino)picolinic acid [ka]

[0310] Step A: To a solution of (R)-6-chloro-3-((1-(2-cyano-3-hydroxy-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (100 mg, 251 micromoles, 1.00 equivalent) and (1-(trifluoromethyl)cyclopropyl)methaneamine hydrochloride (53.3 mg, 251 micromoles, 1.00 equivalent, HCl) in N,N-dimethylformamide (1.00 mL), benzotriazole-1-yloxytris-pyrrolidine o-phosphonium hexafluorophosphate (157 mg, 302 micromoles, 1.20 equivalents) and diisopropylethylamine (162 mg, 1.26 mmol, 219 μL, 5.00 equivalents) was added. The mixture was stirred at 25°C for 12 hours. After the reaction was complete, the mixture was cooled to 15°C and slowly added to water (2.00 mL). During this time, a yellow precipitate formed. The suspension was filtered, the cake was collected and dried under reduced pressure to obtain (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)quinoxaline-5-yl)ethyl)amino)methyl picolinate (45.0 mg, 71.1 micromoles, yield 28.3%, purity 82%) as a yellow solid. LCMS[M+1] + = 519.2

[0311] Step B: To a solution of (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)quinoxaline-5-yl)ethyl)amino)methyl picolinate (45.0 mg, 71.1 micromoles, 1.00 equivalent) in dimethyl sulfoxide (1.00 mL), lithium chloride (30.1 mg, 711 micromoles, 14.6 μL, 10.0 equivalents) was added. The mixture was stirred at 120 °C for 6 hours. After the reaction was complete, the mixture was cooled to 25°C and then purified by preparative HPLC (column: Phenomenex Luna C18 150x25mmx10μm; mobile phase: phase A: 0.225% formic acid in water, phase B: acetonitrile; gradient: 62%-92% phase B) to obtain (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)quinoxaline-5-yl)ethyl)amino)picolinic acid (4.26 mg, 8.40 micromoles, yield 11.8%, purity 99.6%) as a yellow solid. LCMS[M+1] + = 505.2

[0312] 1 H NMR (400MHz, CD3OD) δ=7.57(s,2H), 7.17(d,J=8.8Hz,1H), 6.92(d,J=9.2Hz,1H), 5.65-5.54(m,1 H), 4.14-3.91(m,2H), 2.42(s,3H), 1.68(d,J=6.4Hz,3H), 1.04-0.93(m,4H)

[0313] Example 16 (R)-6-chloro-3-((1-(2-cyano-3-(1,1-difluoro-5-azaspiro[2,3]hexane-5-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid [ka]

[0314] Step A: A solution of (R)-6-chloro-3-((1-(2-cyano-3-hydroxy-7-methylquinoxaline-5-yl)ethyl)amino) methyl picolinate (50.0 mg, 126 micromoles, 1.00 equivalent), benzotriazole-1-yloxytris-pyrrolidine o-phosphonium hexafluorophosphate (98.1 mg, 188 micromoles, 1.50 equivalents), and diisopropylethylamine (81.2 mg, 628 micromoles, 109 μL, 5.00 equivalents) in N,N-dimethylformamide (1.00 mL) was stirred at 20°C for 20 minutes. To the above mixture, 1,1-difluoro-5-azaspiro[2.3]hexane hydrochloride (29.3 mg, 188 micromoles, 1.50 equivalents) was added at 20°C. The reaction mixture was stirred at 20°C for 1 hour. After completion, the mixture was diluted with water (3.00 mL) and extracted with ethyl acetate (3 x 3.00 mL). The organic layers were combined, dried on anhydrous sodium sulfate, and concentrated to obtain a residue. The residue was purified by preparative TLC (SiO2, petroleum ether:ethyl acetate = 1:3) to obtain (R)-6-chloro-3-((1-(2-cyano-3-(1,1-difluoro-5-azaspiro[2.3]hexane-5-yl)-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (55.0 mg, 75.0 micromoles, yield 59.6%, purity 68.0%) as a yellow solid. LCMS[M+1] + =499.2

[0315] Step B: To a solution of (R)-6-chloro-3-((1-(2-cyano-3-(1,1-difluoro-5-azaspiro[2,3]hexane-5-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinate (50.0 mg, 90.2 micromoles, 1.00 equivalent) in dimethyl sulfoxide (1.00 mL), lithium chloride (38.2 mg, 902 micromoles, 10.0 equivalents) was added. The reaction mixture was stirred at 130 °C for 2 hours. After completion, the mixture was cooled to 20 °C. The mixture was filtered, and the filtrate was purified by preparative HPLC (column: YMC-Actus Triart C18 150*30mm*7μm; mobile phase: phase A: 0.225% formic acid in water, phase B: acetonitrile; gradient: 63%-93% phase B) to obtain (R)-6-chloro-3-((1-(2-cyano-3-(1,1-difluoro-5-azaspiro[2.3]hexane-5-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid (14.4 mg, 29.7 micromoles, yield 32.9%, purity 99.9%) as a yellow solid. LCMS[M-1] - =483.0

[0316] 1 H NMR (400MHz, DMSO-d6) δ=12.96(brs,1H), 8.57(brd,J=7.2Hz,1H), 7.66(s,1H), 7.64(s,1H), 7.30(d,J=8.8Hz,1H), 7.09(d,J=8.8Hz, 1H), 5.41(quin,J=12.8Hz,1H), 4.66-4.51(m,4H), 2.41(s,3H), 1.88(brt,J=8.8Hz,2H), 1.66(d,J=6.8Hz,3H)

[0317] 19 F NMR (400MHz, DMSO-d6) δ=-137.62

[0318] Example 17 (R)-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)-6-methylpicolinic acid [ka]

[0319] Step A: Tris(dibenzylideneacetone)dipalladium(0) (24.9 mg, 27.2 micromoles, 0.10 equivalents) was added to a solution of (R)-5-(1-aminoethyl)-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-2-carbonitrilate (100 mg, 272 micromoles, 1.00 equivalent, hydrochloride), methyl 3-bromo-6-methylpicolinate (125 mg, 544 micromoles, 2.00 equivalents), xanthophos (31.5 mg, 54.4 micromoles, 0.20 equivalents), and cesium carbonate (354 mg, 1.09 mmol, 4.00 equivalents) in dioxane (2.00 mL). The mixture was stirred at 100°C for 12 hours under a nitrogen atmosphere. After the reaction was complete, the mixture was cooled to 25°C and then concentrated directly to obtain the residue. The residue was purified by preparative TLC (SiO2, petroleum ether / ethyl acetate = 3:1) to obtain (R)-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)-6-methylpicolinate methyl (100 mg, 208 micromoles, yield 76.6%) as a yellow solid. LCMS[M+1] + =481.2

[0320] Step B: Lithium chloride (79.4 mg, 1.87 mmol, 38.4 μL, 10.0 equivalents) was added to a mixture of (R)-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)-6-methylpicolinate methyl in dimethyl sulfoxide (0.5 mL). The reaction mixture was stirred at 120 °C for 8 hours. After the reaction was complete, the mixture was cooled to 25 °C and then concentrated directly to obtain the residue. The reaction mixture was diluted with water (10.0 mL) and extracted with ethyl acetate (20.0 mL x 2). The organic layers were combined, washed with saturated sodium bicarbonate solution (10.0 mL x 2), dried on anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. The residue was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 1 / 1 to 0 / 1) to obtain (R)-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)-6-methylpicolinic acid (25.6 mg, 53.7 micromoles, yield 28.7%, purity 97.9%) as a yellow solid. LCMS[M+1] + =467.1

[0321] 1 H NMR (400MHz, CDCl3) δ=8.09(brd,J=5.2Hz,1H), 7.58(s,1H), 7.53(s,1H), 6.92(d,J=8.8Hz,1H), 6.61(d,J=8.8Hz,1H), 5.43( quin,J=6.6Hz,1H), 3.88-3.75(m,4H), 2.39(s,3H), 2.31(s,3H), 2.24-2.14(m,4H), 1.61(d,J=6.8Hz,3H)

[0322] Example 18-105

[0323] The compounds listed in Table 1 are essentially prepared according to the operations described in the schemes and examples above, or as described in the schemes and examples immediately below Table 1. Table 1 [Table 3-1] Table 3-2 Table 3-3 Table 3-4

[0324] Table 3-5 Table 3-6 Table 3-7 Table 3-8

[0325] Table 3-9 Table 3-10 Table 3-11 Table 3-12

[0326] Table 3-13 Table 3-14 Table 3-15 Table 3-16

[0327] Table 3-17 Table 3-18 Table 3-19 Table 3-20

[0328] Table 3-21 Table 3-22 Table 3-23 Table 3-24

[0329] Table 3-25 Table 3-26 Table 3-27 Table 3-28

[0330] Table 3-29 Table 3-30 Table 3-31 Table 3-32

[0331] Table 3-33 Table 3-34 Table 3-35 Table 3-36

[0332] Table 3-37 Table 3-38 Table 3-39 Table 3-40

[0333] Table 3-41 Table 3-42 Table 3-43 Table 3-44

[0334] Table 3-45 Table 3-46 Table 3-47 Table 3-48

[0335] Table 3-49 Table 3-50 Table 3-51 Table 3-52

[0336] Table 3-53 Table 3-54 Table 3-55 Table 3-56

[0337] Table 3-57 Table 3-58 Table 3-59 Table 3-60

[0338] Table 3-61 Table 3-62 Table 3-63 Table 3-64

[0339] Table 3-65 Table 3-66 Table 3-67 Table 3-68

[0340] Table 3-69 Table 3-70 Table 3-71 Table 3-72

[0341] Table 3-73 Table 3-74 Table 3-75 Table 3-76

[0342] Table 3-77 Table 3-78 Table 3-79 Table 3-80

[0343] Table 3-81 Table 3-82 Table 3-83 Table 3-84

[0344] Table 3-85 Table 3-86 Table 3-87 Table 3-88

[0345] Table 3-89

Table 3-90

[0346] Table 3-93 Table 3-94 Table 3-95 Table 3-96

[0347] Table 3-97 Table 3-98 Table 3-99 Table 3-100

[0348] Table 3-101 Table 3-102 Table 3-103 Table 3-104

[0349] Table 3-105 Table 3-106 Table 3-107 Table 3-108

[0350] Table 3-109 Table 3-110 Table 3-111 Table 3-112

[0351] Table 3-113 Table 3-114 Table 3-115 Table 3-116

[0352] Table 3-117 Table 3-118 Table 3-119 Table 3-120

[0353] Table 3-121 Table 3-122 Table 3-123 Table 3-124

[0354] Table 3-125 Table 3-126 Table 3-127 Table 3-128

[0355] Table 3-129 Table 3-130 Table 3-131 Table 3-132

[0356] Table 3-133 Table 3-134 Table 3-135 Table 3-136

[0357] Table 3-137 Table 3-138 Table 3-139 Table 3-140

[0358] Table 3-141 Table 3-142 Table 3-143 Table 3-144

[0359] Table 3-145 [Table 3-146] [Table 3-147]

[0360] Synthesis of Examples 47A and 47B 6-Chloro-3-(((1R)-1-(2-Cyano-7-methyl-3-((1S)-1-(trifluoromethyl)-3-azabicyclo[3.1.0]hexane-3-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid, and 6-Chloro-3-(((1R)-1-(2-Cyano-7-methyl-3-((1R)-1-(trifluoromethyl)-3-azabicyclo[3.1.0]hexane-3-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid [ka]

[0361] Step A: To a solution of (R)-6-chloro-3-((1-(2-cyano-3-hydroxy-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (180 mg, 452 micromoles, 1.00 equivalent) in N,N-dimethylformamide (2.00 mL), PyBOP (706 mg, 1.36 mmol, 3.00 equivalent) and N,N-diisopropylethylamine (292 mg, 2.26 mmol, 394 μL, 5.00 equivalent) were added, and the mixture was stirred at 25°C for 30 minutes. To this mixture, 1-(trifluoromethyl)-3-azabicyclo[3.1.0]hexane (127 mg, 679 micromoles, 1.50 equivalent, hydrochloride) was added, and the reaction was stirred at 25°C for 1 hour. The mixture was then diluted with water (10.0 mL) and extracted with ethyl acetate (3 x 10.0 mL). The organic layers were combined, washed with brine (10.0 mL), dried on anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a residue. The residue was purified by preparative TLC (SiO2, petroleum ether:ethyl acetate = 2:1) to obtain 6-chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(1-(trifluoromethyl)-3-azabicyclo[3.1.0]hexane-3-yl)quinoxaline-5-yl)ethyl)amino)picolinate methyl (150 mg, 250 micromoles, yield 55.3%, purity 88.6%) as a yellow solid. LCMS[M+Na] + = 553.1

[0362] Step B: The diastereomer of 6-chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(1-(trifluoromethyl)-3-azabicyclo[3.1.0]hexane-3-yl)quinoxaline-5-yl)ethyl)amino)picolinate methyl (150 mg, purity 88.6%) was separated by SFC (column: Daicel ChiralCell OX (250 mm x 30 mm, 10 μm); mobile phase: phase A: CO2, phase B: 0.1% NH4OH in MeOH; B%: 30%, isocratic elution mode). The desired fractions were concentrated to obtain 6-chloro-3-(((1R)-1-(2-cyano-7-methyl-3-((1S)-1-(trifluoromethyl)-3-azabicyclo[3.1.0]hexane-3-yl)quinoxaline-5-yl)ethyl)amino)picolinate methyl and 6-chloro-3-(((1R)-1-(2-cyano-7-methyl-3-((1R)-1-(trifluoromethyl)-3-azabicyclo[3.1.0]hexane-3-yl)quinoxaline-5-yl)ethyl)amino)picolinate.

[0363] First isomer to elute: white solid (50.0 mg, 84.8 micromoles, yield 18.7%, purity 85.0%), LC-MS[M+1] + =531.3(Rt=0.692 minutes)

[0364] Secondly eluted isomer: white solid (65.0 mg, 110 micromoles, yield 24.4%, purity 90.0%), LC-MS[M+1] + =531.3(Rt=0.688 minutes)

[0365] Step C1: The first eluted methyl ester was saponified with acid using the following procedure: Lithium chloride (39.1 mg, 923 micromoles, 18.9 μL, 10.0 equivalents) was added to a solution of the first eluted methyl ester (49.0 mg, 92.3 micromoles, 1.00 equivalent) in DMSO (0.10 mL), and the mixture was stirred at 130°C for 2 hours. After the reaction was complete, the mixture was cooled to 20°C, filtered, and the filtrate was directly purified by preparative HPLC (column: Phenomenex Luna C18 150x25mmx10μm; mobile phase: phase A: 0.225% formic acid in water, phase B: acetonitrile; gradient: 75%~100% phase B) to obtain the desired acid (Example 43A) (2.31 mg, 4.43 micromoles, yield 4.80%, purity 99.2%) of the first eluted ester from the above reaction as a yellow solid. LCMS[M+Na] + =539.1

[0366] 1 H NMR (400MHz, DMSO-d6) δ=8.66(brs,1H), 7.60(s,2H), 7.24(d,J=8.8Hz,1H), 6.98(brd,J=8.8Hz,1H), 5.43(quin,J=6.8Hz,1H), 4.45-4.28(m,2H) ), 4.12-3.94(m,2H), 2.39(s,3H), 2.38-2.33(m,1H), 1.63(d,J=6.4Hz,3H), 1.43(dd,J=5.2, 8.4Hz,1H), 1.08-0.98(m,1H)

[0367] Process C2: The second eluted methyl ester was saponified to an acid using the following procedure: Lithium chloride (51.1 mg, 1.21 mmol, 10.0 equivalent) was added to a solution of the second eluted methyl ester (64.0 mg, 121 micromoles, 1.00 equivalent) in DMSO (1.00 mL), and the mixture was stirred at 130°C for 2 hours. After the reaction was complete, the mixture was cooled to 20°C, filtered, and the filtrate was directly purified by preparative HPLC (column: Phenomenex Luna C18 150x25 mm x 10 μm; mobile phase: phase A: 0.225% formic acid in water, phase B: acetonitrile; gradient: 75%~100% phase B) to obtain the desired acid of the second eluted ester derived from the above reaction (Example 43B) (9.77 mg, 18.7 micromoles, yield 15.5%, purity 98.7%) as a yellow solid. LCMS[M+Na] + = 539.2

[0368] 1 H NMR (400MHz, DMSO-d6) δ=12.96(brs,1H), 8.46(brd,J=7.2Hz,1H), 7.66-7.56(m,2H), 7.29(d,J=8.8 Hz,1H), 7.11-7.01(m,1H), 5.60-5.27(m,1H), 4.43(d,J=10.8Hz,1H), 4.31(br d,J=11.6Hz,1H), 4.01(td,J=4.8, 10.4Hz,2H), 2.40(s,3H), 2.38-2.31(m,1H) , 1.65(d,J=6.4Hz,3H), 1.44(brdd,J=6.0, 8.4Hz,1H), 1.04(brt,J=5.6Hz,1H)

[0369] Synthesis of Example 58 [ka]

[0370] Step A: To a solution of (R)-6-chloro-3-((1-(2-cyano-3-hydroxy-7-methylquinoxaline-5-yl)ethyl)amino)picolinate (50.0 mg, 113 micromoles, 1.00 equivalent) and morpholine (14.8 mg, 170 micromoles, 14.9 μL, 1.50 equivalents) in DMF (0.50 mL), PyBOP (88.3 mg, 170 micromoles, 1.50 equivalents) and N,N-diisopropylethylamine (43.9 mg, 339 micromoles, 59.1 μL, 3.00 equivalents) were added, and the mixture was stirred at 25°C for 1 hour. After this time, water (1.00 mL) was slowly added to the mixture, and a yellow precipitate was formed. Next, the suspension was filtered, the cake was collected, and dried under vacuum to obtain (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-morpholinoquinoxaline-5-yl)ethyl)amino) methyl picolinate (52.0 mg, 111 micromoles, yield 98.5%) as a yellow solid. LCMS[M+1] + =467.2

[0371] Step B: To a solution of (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-morpholinoquinoxaline-5-yl)ethyl)amino)methyl picolinate (52.0 mg, 111 micromoles, 1.00 equivalent) in DMSO (0.50 mL), lithium chloride (47.2 mg, 1.11 mmol, 22.8 μL, 10.0 equivalent) was added, and the mixture was stirred at 120 °C for 6 hours. Next, the mixture was cooled to 25°C and filtered to obtain a filtrate. This filtrate was purified by preparative HPLC (column: YMC-Actus Triart C18 150x30mmx7μm; mobile phase: Phase A: 0.225% formic acid in water, Phase B: acetonitrile; gradient: 55%~85%B) to obtain (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-morpholinoquinoxaline-5-yl)ethyl)amino)picolinic acid (8.93 mg, 19.3 micromoles, yield 17.4%, purity 98.1%) as a white solid. LCMS[M+1] + =453.2

[0372] 1H NMR (400MHz, CD3OD) δ=7.66(d,J=1.6Hz,1H), 7.63(s,1H), 7.19(d,J=9.2Hz,1H), 7.02(d,J=9.2Hz,1H), 5.53( q,J=6.8Hz,1H), 3.98-3.86(m,4H), 3.83-3.72(m,4H), 2.46(s,3H), 1.73(d,J=6.8Hz,3H)

[0373] Synthesis of Example 70 (R)-6-chloro-3-((1-(2-cyano-3-(3,3-difluoropyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid [ka]

[0374] Step A: To a solution of (R)-6-chloro-3-((1-(2-cyano-3-hydroxy-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (70.0 mg, 158 micromoles, 1.00 equivalent) and 3,3-difluoropyrrolidine (27.3 mg, 190 micromoles, 1.20 equivalents, hydrochloride) in DMF (0.50 mL), PyBOP (124 mg, 238 micromoles, 1.50 equivalents) and N,N-diisopropylethylamine (143 mg, 1.11 mmol, 193 μL, 7.00 equivalents) were added, and the mixture was stirred at 25°C for 12 hours. The mixture was then cooled to 15°C, and water (2.00 mL) was slowly added to form a yellow precipitate. The suspension was filtered, the cake was collected, and dried under vacuum to obtain (R)-6-chloro-3-((1-(2-cyano-3-(3,3-difluoropyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino) methyl picolinate (70.1 mg, 144 micromoles, yield 90.9%) as a yellow solid. LCMS[M+Na] + = 509.2

[0375] Step B: A solution of (R)-6-chloro-3-((1-(2-cyano-3-(3,3-difluoropyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (70.0 mg, 144 micromoles, 1.00 equivalent) in DMSO (2.00 mL) was mixed with lithium chloride (60.9 mg, 1.44 mmol, 29.5 μL, 10.0 equivalent), and the mixture was stirred at 120 °C for 12 hours. The mixture was then cooled to 25 °C, filtered, and the filtrate was collected. The filtrate was purified via preparative HPLC (column: Welch Xtimate C18 150x25mmx5μm; mobile phase: Phase A: 0.225% formic acid in water, Phase B: acetonitrile; gradient: 65%~85%B) to obtain (R)-6-chloro-3-((1-(2-cyano-3-(3,3-difluoropyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid (8.26 mg, 17.2 micromoles, yield 12.0%, purity 98.7%) as a yellow solid. LCMS[M+Na] + =495.1

[0376] 1 H NMR (400MHz, CD3OD) δ=7.60(s,1H), 7.57(s,1H), 7.19(d,J=9.2Hz,1H), 7.02(d,J=9.2Hz,1H), 5.50(q,J= 6.8Hz,1H), 4.38-4.14(m,4H), 2.66-2.55(m,2H), 2.43(s,3H), 1.73(d,J=6.8Hz,3H)

[0377] Synthesis of Examples 94A and 94B

[0378] 6-Chloro-3-(((1R)-1-(2-Cyano-3-((1R)-1-Hydroxy-6-Azaspiro[3.5]nonan-6-yl)-7-Methylquinoxaline-5-yl)ethyl)amino)picolinic acid, and 6-Chloro-3-(((1R)-1-(2-Cyano-3-((1S)-1-Hydroxy-6-Azaspiro[3.5]nonan-6-yl)-7-Methylquinoxaline-5-yl)ethyl)amino)picolinic acid [ka]

[0379] Step A: To a solution of (R)-6-chloro-3-((1-(2-cyano-3-hydroxy-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (80.0 mg, 201 micromoles, 1.00 equivalent) in DMF (1.00 mL), PyBOP (314 mg, 603 micromoles, 3.00 equivalent) and N,N-diisopropylethylamine (130 mg, 1.01 mmol, 175 μL, 5.00 equivalent) were added, and the mixture was stirred at 25°C for 30 minutes. After this time, 6-azaspiro[3.5]nonan-1-ol (42.0 mg, 302 micromoles, 1.50 equivalent) was added to the mixture, and the mixture was stirred at 25°C for 1 hour. After the reaction was complete, the mixture was diluted with water (10.0 mL) and extracted with ethyl acetate (3 x 10.0 mL). The organic layers were combined, washed with brine (10.0 mL), dried on anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by preparative TLC (SiO2, petroleum ether:ethyl acetate = 2:1) to obtain 6-chloro-3-(((1R)-1-(2-cyano-3-(1-hydroxy-6-azaspiro[3.5]nonan-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (35.0 mg, 60.5 micromoles, yield 30.1%, purity 94.9%) as a yellow solid. LCMS[M+1] + = 521.2

[0380] Step B: To a solution of 6-chloro-3-(((1R)-1-(2-cyano-3-(1-hydroxy-6-azaspiro[3.5]nonan-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinate methyl (30.0 mg, 57.6 micromoles, 1.00 equivalent) in DMSO (0.50 mL), lithium chloride (24.4 mg, 576 micromoles, 10.0 equivalents) was added, and the mixture was stirred at 130°C for 5 hours. Next, the mixture was cooled to room temperature and filtered. The filtrate was then purified by direct application to a preparative HPLC (column: Phenomenex Luna C18 150x25mmx10μm; mobile phase: Phase A: 0.225% formic acid in water, Phase B: acetonitrile, gradient: 55%~85%B). The first diastereomer to elute (19.9 mg, 38.6 micromoles, yield 67.0%, purity 98.5%) was obtained as a yellow solid, and the second diastereomer to elute (7.33 mg, 14.2 micromoles, yield 24.7%, purity 98.4%) was also obtained as a yellow solid.

[0381] Characterization data of the first diastereomer to elute: LCMS[M+1] + =507.2 1 H NMR (400MHz, DMSO-d6) δ=8.47(brd,J=5.2Hz,1H), 7.65-7.64(m,1H), 7.63(brs,1H), 7.30-7.27(m,1H), 7.05-6.99(m,1H), 5.53-5.39(m,1H), 4.99-4.89(m ,1H), 3.92-3.69(m,4H), 3.51-3.46(m,1H), 2.41(s,3H), 2.15-2.05(m,1H), 1.90-1.68(m,5H), 1.66-1.64(m,3H), 1.53-1.38(m,2H)

[0382] Characteristic data of the second eluted diastereomer: LCMS[M+1] + =507.2 1H NMR (400MHz, DMSO-d6) δ=8.45(t,J=6.8Hz,1H), 7.66-7.57(m,2H), 7.27(dd,J=4.8, 8.8Hz,1H), 6.98(t,J=9.2Hz ,1H), 5.55-5.44(m,1H), 5.06-4.85(m,1H), 4.21(brdd,J=13.6, 18.8Hz,1H), 3.94-3.85( m,1H), 3.81(t,J=7.6Hz,1H), 3.55(t,J=12.4Hz,1H), 3.47-3.42(m,1H), 2.40(s,3H), 2.1 7-2.06(m,1H), 1.94-1.82(m,1H), 1.81-1.68(m,3H), 1.67-1.57(m,5H), 1.28-1.18(m,1H)

[0383] Synthesis of Examples 109A and 109B 2-(((R)-1-(2-cyano-3-((R)-4,4-difluoro-2-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid, and 2-(((R)-1-(2-cyano-3-((S)-4,4-difluoro-2-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid [ka]

[0384] Step A: To a solution of (R)-2-((1-(2-cyano-3-hydroxy-7-methylquinoxaline-5-yl)ethyl)amino)methyl benzoate (90.0 mg, 248 micromoles, 1.00 equivalent) and 4,4-difluoro-2-methylpyrrolidine (60.2 mg, 497 micromoles, 2.00 equivalent) in DMF (1.00 mL), PyBOP (194 mg, 373 micromoles, 1.50 equivalent) and N,N-diisopropylethylamine (161 mg, 1.24 mmol, 216 μL, 5.00 equivalent) were added, and the mixture was stirred at 25°C for 3 hours. Then the mixture was poured into water (10.0 mL) and stirred for 2 minutes. The suspension was filtered, and the filtered cake was dried under vacuum to obtain the residue. The residue was purified by SFC (column: Daicel Chiral Cell OX (250mm x 30mm, 10μm); mobile phase: Phase A: CO2, Phase B: 0.1% NH4OH in MeOH; B%: 40%) to obtain methyl 2-(((1R)-1-(2-cyano-3-(4,4-difluoro-2-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoate (100mg, 214 micromoles, yield 86.5%) as a yellow oil. LCMS[M+1] + =466.0

[0385] Step B: The diastereomer of 2-(((1R)-1-(2-cyano-3-(4,4-difluoro-2-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)methyl benzoate (100 mg, 215 micromoles, 1.00 equivalent) was further separated by SFC (column: Daicel ChiralCell OX (250 mm x 50 mm, 10 μm); mobile phase: phase A: CO2, phase B: 0.1% NH4OH in MeOH; B%: 17%), and the first eluted methyl ester isomer (40.0 mg, 85.9 micromoles, yield 40.0%) was obtained as a yellow oil, and the second eluted methyl ester isomer (45.0 mg, 96.7 micromoles, yield 45.0%) was also obtained as a yellow oil.

[0386] Step C1: To a solution of the first methyl ester isomer (35.0 mg, 75.2 micromoles, 1.00 equivalent) eluted from Step B in DMSO (2.00 mL), lithium chloride (31.9 mg, 752 micromoles, 15.4 μL, 10.0 equivalents) was added, and the mixture was stirred at 130°C for 8 hours. The mixture was then cooled to 25°C, diluted with a further 20.0 mL of water, and extracted with ethyl acetate (20.0 mL). The organic layers were combined, washed with brine (20.0 mL x 3), dried over sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by preparative HPLC (YMC-Actus Triart C18 150x30mmx7μm; mobile phase: phase A: 0.225% formic acid solution in water, phase B: acetonitrile; gradient: 60%-90%) to obtain 2-(((R)-1-(2-cyano-3-((R)-4,4-difluoro-2-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid or 2-(((R)-1-(2-cyano-3-((S)-4,4-difluoro-2-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid (4.07 mg, 8.73 micromoles, yield 11.6%, purity 96.8%) as a yellow solid. LCMS[M+1] + =452.2

[0387] 1 H NMR (400MHz, CD3OD) δ=7.88(dd,J=1.6, 8.0Hz,1H), 7.63(d,J=1.6Hz,1H), 7.58(s,1H), 7.12-7.06 (m,1H), 6.49(t,J=7.6Hz,1H), 6.36(d,J=8.4Hz,1H), 5.56(q,J=6.8Hz,1H), 5 .09-4.99(m,1H), 4.54-4.41(m,1H), 4.30(q,J=12.0Hz,1H), 2.84-2.72(m,1H ), 2.42(s,3H), 2.39-2.26(m,1H), 1.68(d,J=6.8Hz,3H), 1.51(d,J=6.8Hz,3H)

[0388] Step C1: To a solution of the methyl ester isomer (40.0 mg, 85.9 micromoles, 1.00 equivalent) eluted from Step B in DMSO (1.00 mL), lithium chloride (36.4 mg, 859 micromoles, 17.6 μL, 10.0 equivalents) was added, and the mixture was stirred at 130°C for 8 hours. The mixture was then cooled to 25°C, diluted with a further 20.0 mL of water, and extracted with ethyl acetate (20.0 mL). The organic layers were combined, washed with brine (20.0 mL x 3), dried over sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by preparative HPLC (column: YMC-Actus Triart C18 150x30mmx7μm; mobile phase: Phase A: 0.225% formic acid in water, Phase B: acetonitrile; gradient: 60%~90%B) to obtain 2-(((R)-1-(2-cyano-3-((R)-4,4-difluoro-2-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid or 2-(((R)-1-(2-cyano-3-((S)-4,4-difluoro-2-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid (6.10 mg, 13.1 micromoles, yield 15.3%, purity 97%) as a yellow solid. LCMS[M+1] + =452.2

[0389] 1 1H NMR (400MHz, CD3OD) δ=7.89(d,J=8.0Hz,1H), 7.61(s,1H), 7.58(brs,1H), 7.10-7.03(m,1H), 6. 49(t,J=7.6Hz,1H), 6.33(d,J=8.4Hz,1H), 5.60(q,J=6.8Hz,1H), 4.98-4.90 (m,1H), 4.46(q,J=13.2Hz,1H), 4.31(q,J=12.0Hz,1H), 2.83-2.68(m,1H), 2.41(s,3H), 2.38-2.26(m,1H), 1.61(d,J=6.8Hz,3H), 1.50(d,J=6.0Hz,3H)

[0390] Examples 110A and 110B 6-Chloro-3-(((R)-1-(2-Cyano-3-((R)-3-methoxypyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid, and 6-Chloro-3-(((R)-1-(2-Cyano-3-((S)-3-methoxypyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid [ka]

[0391] Step A: To a solution of (R)-6-chloro-3-((1-(2-cyano-3-hydroxy-7-methylquinoxaline-5-yl)ethyl)amino) methyl picolinate (70.0 mg, 176 micromoles, 1.00 equivalent) and 3-methoxypyrrolidine (35.6 mg, 352 micromoles, 2.00 equivalents) in DMF (1.00 mL), PyBOP (137 mg, 264 micromoles, 1.50 equivalents) and N,N-diisopropylethylamine (159 mg, 1.23 mmol, 215 μL, 7.00 equivalents) were added, and the mixture was stirred at 30°C for 2 hours. Next, the mixture was poured into water (10.0 mL) and stirred for 2 minutes. The resulting suspension was filtered, and the filtered cake was dried under vacuum to obtain 6-chloro-3-(((1R)-1-(2-cyano-3-(3-methoxypyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinate methyl (80.0 mg, 166 micromoles, yield 94.5%) as a yellow oil. LCMS[M+Na] + =503.1

[0392] Step B: Methyl 6-chloro-3-(((1R)-1-(2-cyano-3-(3-methoxypyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinate (80.0 mg, 166 micromoles, 1.00 equivalent) was purified by SFC (column: Welch Ultimate XB-CN 250x50x10 μm; mobile phase: phase A: hexane, phase B: 0.1% NH4OH in EtOH; gradient: 1%~40%B). The first eluted methyl ester isomer (40.0 mg, 83.2 micromoles, yield 50.0%) was obtained as a yellow oil, and the next eluted methyl ester isomer (45.0 mg, 93.6 micromoles, yield 56.3%) was obtained as a yellow oil.

[0393] Step C1: To a solution of the methyl ester isomer (40.0 mg, 83.2 micromoles, 1.00 equivalent) initially eluted from Step B in DMSO (1.00 mL), lithium chloride (35.3 mg, 832 micromoles, 17.1 μL, 10.0 equivalents) was added, and the mixture was stirred at 130°C for 2 hours. The reaction mixture was then cooled to 25°C, the pH was adjusted to 6 with hydrochloric acid (2 M in water, 2.00 mL), and further diluted with water (20.0 mL). The resulting aqueous solution was extracted with ethyl acetate (20.0 mL), the organic layers were combined, washed with brine (20.0 mL x 3), dried over sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by preparative HPLC (column: Phenomenex Luna C18 150x25mmx10μm; mobile phase: Phase A: 0.225% formic acid in water, Phase B: acetonitrile; gradient: 60%~90%B) to obtain 6-chloro-3-(((R)-1-(2-cyano-3-((R)-3-methoxypyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid or 6-chloro-3-(((R)-1-(2-cyano-3-((S)-3-methoxypyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid (2.23 mg, 4.39 micromoles, yield 5.28%, purity 91.9%) as a yellow solid. LCMS[M+1] + =467.2

[0394] 1 H NMR (400MHz, CD3OD) δ=7.55(s,1H), 7.53(s,1H) 7.20(d,J=9.2Hz,1H), 7.02(d,J=8.8Hz,1H), 5.58-5.48(m,1H), 5.52(q,J=6.4Hz,1H), 4.24-4. 16(m,1H), 4.08-3.92(m,4H), 3.41(s,3H), 2.41(s,3H), 2.36-2.08(m,2H), 1.72(d,J=6.8Hz,3H)

[0395] Step C2: To a solution of the methyl ester isomer (10.0 mg, 20.8 micromoles, 1.00 equivalent) eluted from Step B in DMSO (1.00 mL), lithium chloride (8.81 mg, 208 micromoles, 4.26 μL, 10.0 equivalents) was added, and the mixture was stirred at 130°C for 2 hours. The mixture was then cooled to 25°C, the pH was adjusted to 6 with hydrochloric acid (2 M in water, 2.00 mL), and further diluted with water (20.0 mL). The resulting aqueous solution was extracted with ethyl acetate (20.0 mL). The organic layers were combined, washed with brine (20.0 mL x 3), dried on sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by preparative HPLC (column: Phenomenex Luna C18 150x25mmx10μm; mobile phase: Phase A: 0.225% formic acid in water, Phase B: acetonitrile; gradient: 60%~90%B) to obtain 6-chloro-3-(((R)-1-(2-cyano-3-((R)-3-methoxypyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid or 6-chloro-3-(((R)-1-(2-cyano-3-((S)-3-methoxypyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid (1.99 mg, 4.18 micromoles, yield 20.1%, purity 98.1%) as a yellow solid. LCMS[M+1] + =467.3

[0396] 1H NMR (400MHz, methanol-d4) δ=7.56(s,1H), 7.54(s,1H), 7.20(d,J=8.8Hz,1H), 7.02(d,J=9.2Hz,1H), 5.51(q,J=6.8Hz,1H), 4.23-4.17(m ,1H), 4.07-3.92(m,4H), 3.42(s,3H), 2.42(s,3H), 2.33-2.23(m,1H), 2.21-2.08(m,1H), 1.72(d,J=6.8Hz,3H)

[0397] Example 260 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-(()-2-methylmorpholino)quinoxaline-5-yl)ethyl)amino)picolinic acid [ka]

[0398] Step A: To a solution of (R)-6-chloro-3-((1-(2-cyano-3-hydroxy-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (40.0 mg, 101 micromoles, trifluoroacetate) in N,N-dimethylformamide (0.50 mL), PyBOP (78.5 mg, 151 micromoles, 1.50 equivalents) and N,N-diisopropylethylamine (65.0 mg, 503 micromoles, 87.6 μL, 3.00 equivalents) were added, and the mixture was stirred at 25°C for 30 minutes. After this time, (S)-2-methylmorpholine (12.2 mg, 121 micromoles, 1.50 equivalents) was added to the above mixture at 25°C, and the mixture was left to stand and stirred at 25°C for 2.5 hours. After the reaction was complete, the mixture was diluted with water (5.00 mL) and extracted with ethyl acetate (5.00 mL x 3). The organic layers were combined, washed with brine (5.00 mL x 3), dried on anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by preparative TLC (SiO2, petroleum ether / ethyl acetate = 3 / 1) to obtain 6-chloro-3-(((R)-1-(2-cyano-7-methyl-3-((S)-2-methylmorpholino)quinoxaline-5-yl)ethyl)amino)picolinate methyl (25.0 mg, 52.0 micromoles, yield 51.7%) as a yellow solid. LCMS[M+1] + =481.2

[0399] Step B: To a solution of 6-chloro-3-(((R)-1-(2-cyano-7-methyl-3-((S)-2-methylmorpholino)quinoxaline-5-yl)ethyl)amino)picolinate (25.0 mg, 52.0 micromoles, 1.00 equivalent) in DMSO (0.80 mL), lithium chloride (22.0 mg, 520 micromoles, 10.0 equivalent) was added, and the reaction mixture was stirred at 120 °C for 5 hours. After the reaction was complete, the reaction mixture was cooled to 20°C, filtered, and the filtrate was purified by preparative HPLC (column: Phenomenex Luna C18 150x25mmx10μm; mobile phase: Phase A: 0.225% formic acid in water, Phase B: acetonitrile; gradient: 55%~85%B) to obtain 6-chloro-3-(((R)-1-(2-cyano-7-methyl-3-((S)-2-methylmorpholino)quinoxaline-5-yl)ethyl)amino)picolinic acid (5.95 mg, 12.7 micromoles, yield 24.4%, purity 99.7%) as a yellow solid. LCMS[M+1] + =467.1

[0400] 1 H NMR (400MHz, CD3OD) δ=7.66(s,2H), 7.21(d,J=8.8Hz,1H), 7.04(d,J=8.8Hz,1H), 5.53(q,J=6.8Hz,1H), 4.29-4.19(m,2H), 4.05(dd,J=2.0, 11.6Hz,1 H), 3.91-3.81(m,2H), 3.28-3.22(m,1H), 2.97(dd,J=10.0, 12.8Hz,1H), 2.47(s,3H), 1.73(d,J=6.8Hz,3H), 1.26(d,J=6.0Hz,3H)

[0401] Examples 261A, 261B, 261C, and 261D 6-Chloro-3-(((R)-1-(2-Cyano-3-((S)-3-((S)-1-hydroxyethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid, 6-Chloro-3-(((R)-1-(2-Cyano-3-((S)-3-((R)-1-hydroxyethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid, 6 -Chloro-3-(((R)-1-(2-cyano-3-((R)-3-((S)-1-hydroxyethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid, and 6-Chloro-3-(((R)-1-(2-cyano-3-((R)-3-((R)-1-hydroxyethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid [ka]

[0402] (R)-6-chloro-3-((1-(2-cyano-3-hydroxy-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate (600 mg, 1.51 mmol, 1.00 equivalent) and N,N-diisopropylethylamine (975 mg, 7.54 mmol, 1.31 mL, 5.00 equivalent) were dissolved in N,N-dimethylformamide (6.00 mL). PyBOP (1.18 g, 2.26 mmol, 1.50 equivalent) was added to the mixture, and the mixture was stirred at 25°C for 1 hour. After this time, 1-(piperidine-3-yl)ethane-1-ol (292 mg, 2.26 mmol, 1.50 equivalent) was added to the mixture at 25°C, and the reaction was further stirred at 25°C for 12 hours. After the reaction was complete, the mixture was diluted with water (100 mL) and extracted with ethyl acetate (3 x 100 mL). The organic layers were combined, washed with brine (100 mL), dried on anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by column chromatography (SiO2, petroleum ether:ethyl acetate = 1:0~3:1) to obtain the crude product. The crude product was then purified by preparative HPLC (column: Phenomenex Luna C18 150x40mmx15μm; mobile phase: phase A: 0.225% formic acid in water, phase B: acetonitrile; gradient: 60%~90%B) to obtain a mixture of the first eluted methyl esters of 261A and 261D (100 mg, 173 micromoles, yield 11.5%) as a yellow solid, and a second peak. The second peak was purified by preparative HPLC (column: YMC-Actus Triart C18 150x30mmx7μm; mobile phase: Phase A: 0.225% formic acid in water, Phase B: acetonitrile; gradient: 63%~93%B), and a mixture of the second eluted methyl esters of 261B and 261C (90.0 mg, 172 micromoles, yield 11.4%) was obtained as a yellow solid. LCMS[M+1] + = 509.2

[0403] A mixture of the first eluting methyl esters of 261A and 261D (100 mg, 173 micromoles, yield 11.5%) was separated by SFC (column: Daicel Chiral Pack IC (250 mm x 30 mm, 10 μm); mobile phase: phase A: CO2, phase B: i-PrOH (0.1% NH3H2O); B%: 55%, isocratic elution). The desired fractions were collected and concentrated under reduced pressure to obtain methyl ester of 261A (25.0 mg, 49.1 micromoles, yield 3.26%) as a white solid, and methyl ester of 261B (43.0 mg, 82.0 micromoles, yield 5.43%) as a yellow solid. Methyl ester of 261A: LCMS[M+Na] + = 531.2 Methyl ester of 261D: LCMS[M+Na] + = 531.2

[0404] A mixture of the second eluting methyl esters of 261B and 261C (90.0 mg, 172 micromoles, yield 11.4%) was separated by SFC (column: Daicel Chiral Pack IC (250 mm x 30 mm, 10 μm); mobile phase: phase A: CO2, phase B: i-PrOH (0.1% NH3H2O); B%: 55%, isocratic elution). The desired fractions were collected and concentrated under reduced pressure to obtain methyl ester of 261B (22.0 mg, 43.2 micromoles, yield 2.87%) as a white solid and methyl ester of 261C (45.0 mg, 88.4 micromoles, yield 5.86%) as a white solid. Methyl ester of 261B: LCMS[M+Na] + = 531.2 Methyl ester of 261C: LCMS[M+Na] + = 531.2

[0405] Lithium chloride (20.0 mg, 472 micromoles, 9.67 μL, 10.0 equivalents) was added to a solution of methyl ester of 261A (24.0 mg, 47.1 micromoles, 1.00 equivalent) in DMSO (0.500 mL). The reaction mixture was stirred at 130 °C for 4 hours. After the reaction was complete, the mixture was cooled to 20 °C. The mixture was then filtered, and the filtrate was purified by preparative HPLC (column: Phenomenex Luna C18 150 x 25 mm x 10 μm; mobile phase: phase A: 0.225% formic acid in water, phase B: acetonitrile; gradient: 55%~85% B) to obtain 261A (11.3 mg, 22.6 micromoles, yield 48.0%) as a yellow solid.

[0406] 1 H NMR (400MHz, DMSO-d6) δ=12.99(s,1H), 8.47(brd,J=6.4Hz,1H), 7.79-7.50(m,2H), 7.29(d,J=8.8Hz,1H), 6.99(d ,J=9.2Hz,1H), 5.46(t,J=6.8Hz,1H), 4.64-4.41(m,1H), 4.33(brd,J=12.8Hz,2H), 3.53(b rt,J=6.4Hz,1H), 3.08(brt,J=11.6Hz,1H), 2.96-2.83(m,1H), 2.41(s,3H), 1.98(brd,J=1 0.0Hz,1H), 1.90-1.77(m,1H), 1.70-1.54(m,5H), 1.41-1.27(m,1H), 1.12(d,J=6.4Hz,3H) LCMS[M+Na] + =517.4

[0407] Lithium chloride (18.3 mg, 432 micromoles, 8.86 μL, 10.0 equivalents) was added to a solution of methyl ester of 261B (22.0 mg, 43.2 micromoles, 1.00 equivalent) in DMSO (0.500 mL). The reaction mixture was stirred at 130 °C for 4 hours. After the reaction was complete, the mixture was cooled to 20 °C. The mixture was then filtered, and the filtrate was purified directly by preparative HPLC (column: Phenomenex Luna C18 150 x 25 mm x 10 μm; mobile phase: phase A: 0.225% formic acid in water, phase B: acetonitrile; gradient: 58%~88% B) to obtain 261B (13.5 mg, 83.0 micromoles, yield 61.4%) as a yellow solid.

[0408] 1 H NMR (400MHz, DMSO-d6) δ=13.00(brs,1H), 8.46(brd,J=7.2Hz,1H), 7.64(d,J=6.0Hz,2H), 7.29(d,J=8.8Hz,1H), 7.02(d,J=8.8Hz,1H), 5.50(brt,J=6.8Hz,1H), 4.52(brd,J=11.6Hz,2H), 4.27(brd,J=12 .0Hz,1H), 3.54-3.43(m,1H), 3.12(brt,J=11.6Hz,1H), 2.99(dd,J=10.4, 13.2Hz,1H), 2. 41(s,3H), 1.88-1.73(m,2H), 1.71-1.55(m,5H), 1.42-1.29(m,1H), 1.10(d,J=6.4Hz,3H) LCMS[M+Na] + =517.4

[0409] Lithium chloride (37.5 mg, 884 micromoles, 18.1 μL, 10.0 equivalents) was added to a solution of methyl ester of 261C (45.0 mg, 88.4 micromoles, 1.00 equivalent) in DMSO (0.500 mL). The reaction mixture was stirred at 130 °C for 4 hours. After the reaction was complete, the mixture was cooled to 20 °C. The mixture was then filtered, and the filtrate was purified directly by preparative HPLC (column: C18 150 x 30 mm; mobile phase: phase A: 0.225% formic acid in water, phase B: acetonitrile; gradient: 62%~92% B) to obtain 261C (12.6 mg, 25.3 micromoles, yield 28.6%) as a yellow solid.

[0410] 1 H NMR (400MHz, DMSO-d6) δ=13.01(brs,1H), 8.45(d,J=7.2Hz,1H), 7.67-7.58(m,2H), 7.29(d,J=8.8Hz,1H), 7.0 0(d,J=9.2Hz,1H), 5.50(quin,J=6.8Hz,1H), 4.52(brd,J=12.4Hz,2H), 4.26(brd,J=13. 2Hz,1H), 3.48(brt,J=6.4Hz,1H), 3.19-3.11(m,1H), 2.98(dd,J=10.4, 13.2Hz,1H), 2.4 1(s,3H), 1.87-1.71(m,2H), 1.69-1.57(m,5H), 1.43-1.30(m,1H), 1.11(d,J=6.4Hz,3H) LCMS[M+Na] + =517.4

[0411] Lithium chloride (29.2 mg, 688 micromoles, 14.1 μL, 10.0 equivalents) was added to a solution of 6-chloro-3-(((R)-1-(2-cyano-3-((R)-3-((R)-1-hydroxyethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinate methyl (35.0 mg, 68.8 micromoles, 1.00 equivalent) in DMSO (0.500 mL). The reaction mixture was stirred at 130 °C for 4 hours. After the reaction was complete, the mixture was cooled to 20 °C. Next, the mixture was filtered, and the filtrate was purified by direct preparative HPLC (column: Phenomenex Luna C18 150x25mmx10μm; mobile phase: phase A: 0.225% formic acid in water, phase B: acetonitrile; gradient: 58%~88%B) to obtain 261D (8.73 mg, 17.5 micromoles, yield 25.4%) as a yellow solid.

[0412] 1 H NMR (400MHz, DMSO-d6) δ=13.04(s,1H), 8.49(brd,J=6.4Hz,1H), 7.71-7.60(m,2H), 7.30(d,J=8.8Hz,1H), 7. 01(d,J=8.8Hz,1H), 5.47(t,J=6.8Hz,1H), 4.61-4.45(m,1H), 4.41-4.26(m,2H), 3.54- 3.47(m,1H), 3.11-3.01(m,1H), 2.93(dd,J=11.6, 12.8Hz,1H), 2.41(s,3H), 2.03-1.95 (m,1H), 1.89-1.78(m,1H), 1.70-1.55(m,5H), 1.40-1.21(m,1H), 1.10(d,J=6.4Hz,3H) LCMS[M+Na] + =517.4

[0413] Examples 262-572

[0414] The compounds listed in Table 2 are essentially prepared according to the operations described in the scheme and examples above. Table 2 [Table 4-1] Table 4-2 Table 4-3 Table 4-4

[0415] Table 4-5 Table 4-6 Table 4-7 Table 4-8

[0416] Table 4-9 Table 4-10 Table 4-11 Table 4-12

[0417] Table 4-13 Table 4-14 Table 4-15 Table 4-16

[0418] Table 4-17 Table 4-18 Table 4-19 Table 4-20

[0419] Table 4-21 Table 4-22 Table 4-23 Table 4-24

[0420] Table 4-25 Table 4-26 Table 4-27 Table 4-28

[0421] Table 4-29 Table 4-30 Table 4-31 Table 4-32

[0422] Table 4-33 Table 4-34 Table 4-35 Table 4-36

[0423] Table 4-37 Table 4-38 Table 4-39 Table 4-40

[0424] Table 4-41 Table 4-42 Table 4-43 Table 4-44

[0425] Table 4-45 Table 4-46 Table 4-47 Table 4-48

[0426] Table 4-49 Table 4-50 Table 4-51 Table 4-52

[0427] Table 4-53 Table 4-54 Table 4-55 Table 4-56

[0428] Table 4-57 Table 4-58 Table 4-59 [Table 4-60]

[0429] [Table 4-61] [Table 4-62] [Table 4-63]

[0430] Examples 573-846 The compounds listed in Table 3 are essentially prepared according to the procedures described in the scheme and examples above. Table 3 [Table 5-1] [Table 5-2] [Table 5-3] [Table 5-4]

[0431] [Table 5-5] [Table 5-6] [Table 5-7] [Table 5-8]

[0432] [Table 5-9] Table 5-10 Table 5-11 Table 5-12

[0433] Table 5-13 Table 5-14 Table 5-15 Table 5-16

[0434] Table 5-17 Table 5-18 Table 5-19 Table 5-20

[0435] Table 5-21 Table 5-22 Table 5-23 Table 5-24

[0436] Table 5-25 Table 5-26 Table 5-27 Table 5-28

[0437] Table 5-29 Table 5-30 Table 5-31 Table 5-32

[0438] Table 5-33 Table 5-34 Table 5-35 Table 5-36

[0439] Table 5-37 Table 5-38 Table 5-39 Table 5-40

[0440] Table 5-41 Table 5-42 Table 5-43 Table 5-44

[0441] Table 5-45 Table 5-46 Table 5-47 Table 5-48

[0442] Table 5-49 Table 5-50 Table 5-51 Table 5-52

[0443] Table 5-53 Table 5-54 Table 5-55 Table 5-56

[0444] Table 5-57 Table 5-58 Table 5-59 Table 5-60

[0445] Table 5-61 Table 5-62 Table 5-63 Table 5-64

[0446] Table 5-65 Table 5-66 Table 5-67 [Table 5-68] [Table 5-69]

[0447] Examples 847-859 The compounds listed in Table 4 are essentially prepared according to the operations described in the scheme and examples above. Table 4 [Table 6-1] [Table 6-2] [Table 6-3] [Table 6-4]

[0448] [Table 6-5] [Table 6-6] [Table 6-7]

[0449] Example A

[0450] This example demonstrates that a representative compound of the present invention inhibits the formation of phospho-AKT (pAKT) in cells.

[0451] The ability of the compound of formula (I) to inhibit pAKT formation was measured using the alphaLISA Surefire Ultra AKT 1 / 2 / 3 (pS473) Assay Kit (#ALSU-PAKT-B50K) obtained from Perkin Elmer (Waltham, MA).

[0452] To prepare assay plates for the pAKT alphaLISA assay, cells were trypsinized, resuspended in fresh medium, and viable cells were counted using the trypan blue exclusion method. Before seeding, cells were washed with PBS and resuspended in HBSS (Gibco, catalog no. 14025092). T47D (12,000 / w), SKBR3 (12,000 / w), or MKN1 (24,000 / w) cells were seeded at 12 μl per well in solid white flat-bottom 384 cell culture plates (PerkinElmer, #6007680).

[0453] Immediately after seeding, the compound was administered to the cells at an initial concentration of 10.4 μM using an Echo Liquid Handler (Beckman Coulter), and then serially diluted (1:4) to a total of 10 different concentrations. Each assay plate contained a 14-well vehicle (DMSO) and a 14-well positive control (Alpelisib @ 3.125 μM). The cells were incubated with the compound (solubilized in DMSO) at 37°C for approximately 24 hours. After 24 hours of treatment, the cells were lysed with 3 μl of 5x lysis buffer (provided) and incubated on a microtiter plate shaker at room temperature for 15 minutes. After thoroughly lysing the cells, 7.5 μl of acceptor bead mix (prepared using the manufacturer's recommended dilution ratio) was added to each well and allowed to stand on a microtiter plate shaker for 1 minute. The plate was then incubated at room temperature for 1 hour in the dark. After incubation with the acceptor bead mix for 1 hour, 7.5 μl of donor bead mix (prepared using the manufacturer's recommended dilution ratio) was added to each well and allowed to stand on a microtiter plate shaker for 1 minute. The plate was then incubated at room temperature overnight in the dark. The plates were then imaged the following day using a CLARIOstar microplate reader (BMG Labtech, Germany).

[0454] The percentage of the control value was calculated by subtracting the mean signal from the positive control (alperisib) treated well from all treated wells (including the DMSO control well), and then dividing by the mean signal from the vehicle DMSO treated control well. The percentage of the vehicle control value was plotted as log(inhibitor) vs. response-variable slope (4 parameters) for curve fitting, and the IC50 value was measured using XLfit.

[0455] The results are shown in the table below. Note: ND = Not measured Table A Representative compounds of formula (I) Inhibition of pAKT in T47D (PI3Kα H1047R mutant) cells [Table 7-1] [Table 7-2] [Table 7-3]

[0456] [Table 7-4] [Table 7-5] [Table 7-6]

[0457] Table B Representative compounds of formula (I) Inhibition of pAKT in SKBR3 (PI3Kα wild-type) cells [Table 8]

[0458] Example B This example demonstrates that a representative compound of the present invention reduces cell viability. The ability of the compound of formula (I) to reduce cell viability was measured using the CellTiter-Glo 2.0 (CTG) Luminescent Cell Viability Assay (#G9241) obtained from Promega (Madison, WI).

[0459] To prepare assay plates for viability assays, cells were trypsinized, resuspended in fresh medium, and viable cells were counted using the trypan blue exclusion method. T47D, SKBR3, or MKN1 cells were seeded at a rate of 1000 cells per well in a solid white flat-bottom 384 cell culture plate (PerkinElmer, #6007680) at 30 μl and incubated overnight at 37°C.

[0460] On day 1 of the assay, the compound was administered to cells at a starting concentration of 10 μM using an echo liquid handler (Beckman Coulter), and then serially diluted (1:4) to a total of 10 different concentrations. The cells were incubated with the compound (solubilized in DMSO) at 37°C for approximately 72 hours. After 72 hours of treatment, the cell plates were brought to equilibrium at room temperature, then 15 μl of CTG was added to each well, the plates were then covered with aluminum foil to block light, and incubated on a microtiter plate shaker at room temperature for 30 minutes, with luminescence readings collected using a CLARIOstar microplate reader (BMG Labtech, Germany). Percentages of vehicle control values ​​were plotted as log(inhibitor) vs. response-variable slope (4 parameters) for curve fitting, and IC50 values ​​were measured using XLfit.

[0461] Table C Representative compounds of formula (I) Survival rate in T47D (PI3Kα H1047R mutant) cells [Table 9-1] [Table 9-2] [Table 9-3]

[0462] [Table 9-4] [Table 9-5]

[0463] Table D Representative compounds of formula (I) Survival capacity of SKBR3 (PI3Kα wild-type) cells [Table 10-1] [Table 10-2] [Table 10-3]

[0464] [Table 10-4] [Table 10-5]

[0465] The examples and embodiments described herein are for illustrative purposes only, and various modifications or changes thereto will be suggested to those skilled in the art and should be incorporated into the spirit and scope of this application and the attached claims. All publications, patents and patent applications referenced herein are incorporated herein by attribution for all purposes.

Claims

1. Equation (I): 【Chemistry 1】 [In the formula: R １ H, C １ -C ３ Alkyl, or C ３ -C ６ It is a cycloalkyl; R ２ is a phenyl or a 5-6 membered heteroaryl group, where phenyl and heteroaryl each have 1-5 R １２ It may be replaced with; R １２ is, independently of each other, C １ -C ４ alkyl, -OR Ａ -C(O)OR Ａ , (C １ -C ３ alkyl)-OR Ａ -C(O)N(R Ａ ) ２ is cyano, or halogen; R Ａ These are H and C, respectively, independently. １ -C ６ Alkyl, C ３ -C ６ It is a cycloalkyl or 2-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-6-yl; R ３ C may be substituted, polysubstituted, or oversubstituted with fluoropolymers. １ -C ３ Alkyl, C ３ -C ６ Cycloalkyl, C １ -C ３ Alkenil, C ２ -C ３ Alkinyl, or C ５ -C ６ It is a cycloalkenyl; R ４ H, halogen, C １ -C ３ Alkyl, C １ -C ６ Alkoxy, C ３ -C ６ Cycloalkyl, C １ -C ３ Alkenil, C ２ -C ３ Alkinyl or C ５ -C ６ A cycloalkenyl or cyano, where C １ -C ３ Alkyl and C ３ -C ６ Each cycloalkyl group may be substituted with 1 to 5 halo groups; R ６ and R ６Ａ H or C １ -C ６ Represents alkyl; R ５ is hydrogen, -OR ２０ , -SR ２０ , C １ -C ６ Alkyl, halogen, hydroxy, cyano, halo C １ -C ３ Alkyl, hydroxy C １ -C ６ Alkyl, C １ -C ６ Alkoxy, C １ -C ６ Alkoxy (C １ -C ６ ) alkyl, cyano, amino, mono or di(C) １ -C ３ ) Alkylamino, C ３ -C ６ Cycloalkyl, C ３ -C ６ Cycloalkyl (C １ -C ３ Alkyl, 3-8 membered heterocyclyl, phenyl, or 5-6 membered heteroaryl, where alkyl, alkenyl, cycloalkyl, phenyl, 3-8 membered heterocyclyl, and heteroaryl each contain 1-3 halogens, hydroxyl, C １ -C ３ Alkyl, C １ -C ３ Alkoxy, Halo C １ -C ３ Alkyl, hydroxy C １ -C ６ Alkyl, oxo, cyano, amino, mono, or di(C) １ -C ３ ) may be independently substituted with alkylamino compounds. Here, R ２０ is aryl, aryl(C １ -C ６ )alkyl, a 5- to 7-membered heteroaryl, or a 5- to 7-membered heteroaryl(C １ -C ６ )alkyl, where aryl and heteroaryl are each independently substituted with 1 to 4 C １ -C ６ alkyl, halogen, hydroxy, cyano, halo C １ -C ３ alkyl, hydroxy C １ -C ６ alkyl, C １ -C ６ alkoxy, C １ -C ６ alkoxy(C １ -C ６ )alkyl, cyano, amino, or mono- or di(C １ -C ３ )alkylamino; R ５Ａ NR ７ R ８ , C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, C ３ -C ６ Cycloalkyl (C １ -C ３ This represents an alkyl, phenyl, or 5-6 member heteroaryl group, where C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, C ３ -C ６ Cycloalkyl (C １ -C ３ Alkyl), phenyl, and heteroaryl each contain 1 to 3 halogens, halo(C) １ -C ３ Alkyl), hydroxy, oxo, C １ -C ３ Alkyl, C １ -C ３ Alkoxy, C １ -C ６ Alkanoyl, cyano, amino, or mono or di(C) １ -C ３ ) may be independently substituted with alkylamino compounds; R ７ is H or C １ -C ３ Represents alkyl; R ８ H, C １ -C ６ Alkyl, C ２ -C ６ Alkenil, C ３ -C ６ Cycloalkyl, C ３ -C ６ Cycloalkyl (C １ -C ３ alkyl), 3-8 membered heterocyclyl, 3-8 membered heterocyclyl (C １ -C ６ ) alkyl, phenyl (C １ -C ６ ) alkyl, or 5-6 member heteroaryl (C １ -C ６ ) represents alkyl, where C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, C ３ -C ６ Cycloalkyl (C １ -C ３ Alkyl), phenyl, heteroaryl, and 3- to 8-membered heterocyclyls each contain 1 to 3 halogens, halo(C) １ -C ３ Alkyl), hydroxy, oxo, C １ -C ３ Alkyl, C １ -C ３ Alkoxy, cyano, amino, mono, or di(C) １ -C ３ ) Alkylamino, amino or mono or di(C １ -C ３ ) Alkylaminocarbonyl, -SO ２ R １６ , -SO ２ (NR １６ ) ２ , or -NR １７ SO ２ R １６ It may be substituted independently, where R １６ Each of them is independently C １ -C ６ It is alkyl, R １７ is C １ -C ６ It is alkyl; or R ７ and R ８ These, together with the nitrogen atoms to which they bind, form ring Q. Here, the environment Q is A 3-8 member monocyclic heterocyclyl group, where the heterocyclyl group may be condensed with an aromatic or non-aromatic ring containing 3-6 ring members, of which 1 or 2 may be nitrogen, oxygen, or sulfur atoms, and the rest may be carbon; or Carbon atoms from a monocyclic heterocyclyl group or fused ring system, together with further carbons and heteroatoms, form a spirocyclic ring system having a total of up to 10 ring members, where each ring member is a carbon or one or two heteroatoms selected from nitrogen, sulfur, and oxygen atoms. Here, each ring Q is an aromatic or non-aromatic moiety, with 1 to 4 R ９ It may be substituted with the base, where R ９ Each of them is independent of (i) C １ -C ３ C may be substituted with alkoxy. １ -C ６ Alkyl, (ii) C １ -C ６ Alkoxy, (iii) C ３ -C ６ Cycloalkyl, (iv) cyano, (ii) hydroxy, (v) oxo, (vi) halogen, (vii) halo C １ -C ３ Alkyl, (viiii)hydroxy C １ -C ６ Alkyl, (ix)amino, (x)mono or di-(C) １ -C ６ (alkyl)amino (where one alkyl group may optionally be substituted with an oxo group), (xi) 1 or 2 C １ -C ３ Alkyl, C １ -C ３ Alkoxy, C ３ -C ６ Cycloalkyl, cyano, hydroxy, oxo, halogen, halo C １ -C ３ Alkyl, hydroxy C １ -C ３ Alkyl, amino, mono, or di (C) １ -C ６ Alkyl)amino, C ３ -C ６ C may be substituted with cycloalkyl, phenyl, or 5-6 member heteroaryl groups. ２ -C ６ Alkanoyl (where C on Alkanoyl) １ -C ３ Alkyl or C ３ -C ６ The cycloalkyl group may be substituted with a halogen, hydroxyl, or amino group, and the cycloalkyl, phenyl, and heteroaryl groups on the alkanoyl group are each C １ -C ６ Alkyl, C １ -C ６ (May be substituted with alkoxy, halogen, amino, hydroxy, or cyano), (xi)C ３ -C ６ Cycloalkyloxy, (xiiii)phenyl, (xiv)phenyl (C １ -C ３ Alkanoyl), (xv) 5-7 membered heterocyclyl, or (xvi) 5-6 membered heteroaryl, where each phenyl, 5-7 membered heterocyclyl, and 5-6 membered heteroaryl contains 1-4 C １ -C ３ Alkyl, C １ -C ３ Alkoxy, halogen, hydroxy, cyano, oxo, amino, mono or di(C) １ -C ３ Alkyl)amino, amino(C １ -C ３ ) alkyl, mono or di(C) １ -C ３ Alkyl)amino(C １ -C ３ ) alkyl, or amino- or mono or di(C) １ -C ３ (May be substituted with alkylaminocarbonyl) The compound indicated by, or its pharmaceutically acceptable salt or deuterated form.

2. R ６ and R ６Ａ The compound according to claim 1, wherein represents hydrogen.

3. R ６ and R ６Ａ One side represents hydrogen, and the other side represents C １ -C ６ The compound according to claim 1, representing an alkyl group.

4. R ６ and R ６Ａ One side represents hydrogen, and the other side represents C １ -C ６ The compound according to claim 1, representing an alkyl group.

5. R ６ and R ６Ａ However, independently, C １ -C ６ The compound according to claim 1, representing an alkyl group.

6. R １ The compound according to any one of claims 1 to 5, wherein is H.

7. R １ ga CH ３ The compound according to any one of claims 1 to 5.

8. R １ is H or CH ３ The compound according to any one of claims 1 to 5.

9. R ２ is a phenyl or a 5- to 7-membered heteroaryl, each of which has 1, 2, or 3 R １２ A compound according to any one of claims 1 to 8, which is substituted with a group.

10. R ２ is a phenyl or a 5- to 7-membered heteroaryl, each having 1, 2, or 3 R １２ Substituted with at least one R １２ The base is -C(O)OR Ａ The compound according to any one of claims 1 to 8.

11. R ２ is phenyl, pyridinyl, thienyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, imidazolyl, pyrazolyl, pyrazinyl, pyridadinyl, or pyrimidinyl, each of which has 1 to 5 R １２ The compound according to any one of claims 1 to 8, which may be substituted with

12. R ２ is phenyl or pyridinyl, each of which has 1 to 5 R １２ The compound according to any one of claims 1 to 8, which may be substituted with

13. R ２ is phenyl or pyridinyl, each of which has 1 to 5 R １２ It may be replaced by at least one R １２ The base is -C(O)OR Ａ The compound according to any one of claims 1 to 8.

14. R ３ C １ -C ３ The compound according to any one of claims 1 to 10, wherein the alkyl group is unsubstituted, substituted with 1 to 5 halo groups, or perfluorinated.

15. R ３ C １ -C ３ The compound according to any one of claims 1 to 10, wherein the alkyl group is unsubstituted, substituted with 1 to 5 halo groups, or perfluorinated.

16. R ３ C １ -C ３ The compound according to any one of claims 1 to 10, wherein it is alkyl.

17. R ３ Is it ethyl, or R ３ The compound according to any one of claims 1 to 10, wherein is methyl.

18. R ５ is hydrogen, C １ -C ３ Alkyl, Halo C １ -C ３ Alkyl, halogen, cyano, C ３ -C ６ Cycloalkyl, or C ３ -C ６ Cycloalkyl (C １ -C ３ The compound according to any one of claims 1 to 17, wherein it is alkyl.

19. R ５ is a phenyl or a 5-6 member heteroaryl, where each cycloalkyl, phenyl, and heteroaryl is a halogen, hydroxyl, C １ -C ３ Alkyl, C １ -C ３ Alkoxy, cyano, amino, or mono or di(C) １ -C ３ The compound according to any one of claims 1 to 17, which may be substituted with an alkylamino.

20. R ５ is hydrogen, C １ -C ３ Alkyl, Halo C １ -C ３ Alkyl, halogen, cyano, cyclopropyl, or cyclopropyl (C) １ -C ２ The compound according to any one of claims 1 to 17, wherein it is alkyl.

21. R ５ The compound according to any one of claims 1 to 17, wherein the compound is methyl, ethyl, cyclopropyl, or cyano.

22. R ５ The compound according to any one of claims 1 to 17, wherein is methyl or cyano.

23. R ５ However, C １ -C ３ Alkyl, halogen, cyano, cyclopropyl, or cyclopropyl (C) １ -C ２ The compound according to any one of claims 1 to 17, wherein it is alkyl.

24. R ５ The compound according to any one of claims 1 to 17, wherein the compound is hydrogen, halogen, hydroxyl, cyano, or amino.

25. R ５ The is a phenyl or a 5-6 member heteroaryl, where each of the cycloalkyl, phenyl, and heteroaryl is a halogen, hydroxyl, C １ -C ２ Alkyl, C １ -C ２ Alkoxy, cyano, amino, or mono or di(C) １ -C ２ The compound according to any one of claims 1 to 17, which may be substituted with an alkylamino.

26. R ５ The is a phenyl or a 5-6 member heteroaryl, where each of the cycloalkyl, phenyl, and heteroaryl is a halogen, hydroxyl, C １ -C ２ Alkyl, C １ -C ２ Alkoxy, cyano, amino, or mono or di(C) １ -C ２ The compound according to any one of claims 1 to 17, which may be substituted with an alkylamino.

27. R ２ The compound according to any one of claims 1 to 26, wherein the phenyl is substituted.

28. R ２ The compound according to any one of claims 1 to 26, wherein the pyridinyl may be substituted.

29. R ４ The compound according to any one of claims 1 to 27, wherein the compound is hydrogen, fluoro, chloro, methyl, ethyl, trifluoromethyl, or cyano.

30. R ４ The compound according to any one of claims 1 to 27, wherein the compound is hydrogen, fluoro, chloro, methyl, ethyl, trifluoromethyl, or cyano.

31. R ４ The compound according to any one of claims 1 to 27, wherein the compound is fluoro, chloro, methyl, cyclopropyl, or cyano.

32. R ４ The compound according to any one of claims 1 to 27, wherein is fluoro, methyl, or cyano.

33. R ５Ａ However, C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, or C ３ -C ６ Cycloalkyl (C １ -C ３ A compound according to any one of claims 1 to 32, representing an alkyl group.

34. R ５Ａ NR ７ R ８ A compound according to claims 1 to 32, which represents the compound.

35. R ７ is hydrogen, R ８ is hydrogen, C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, or C ３ -C ６ Cycloalkyl (C １ -C ３ The compound according to claim 34, which represents alkyl.

36. R ７ and R ８ However, together with the nitrogen atoms to which they bond, they form ring Q, and here ring Q A monocyclic heterocyclyl group having 3 to 7 members, The R group has 1 to 4 heterocyclyl groups. ９ It may be substituted with the base, where R ９ However, each is independent of C １ -C ６ Alkyl, C １ -C ６ Alkoxy, C ３ -C ６ Cycloalkyl, cyano, hydroxy, oxo, halogen, halo C １ -C ３ Alkyl, hydroxy C １ -C ６ Alkyl, amino, mono, or di (C) １ -C ６ Alkyl)amino, or phenyl or phenyl (C) １ -C ３ Alkanoyl) (where each phenyl is C １ -C ３ Alkyl, C １ -C ３ Alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C) １ -C ３ It is alkyl (may be substituted with amino), The compound according to claim 34.

37. R ７ and R ８ However, together with the nitrogen atoms they bond to, they form ring Q, and here ring Q, A monocyclic heterocyclyl group having 3 to 7 members, The heterocyclyl group is condensed into an aromatic or non-aromatic ring containing 3 to 6 ring members, of which 1 or 2 may be nitrogen atoms and the rest carbon atoms, where The condensed heterocyclyl group has 1 to 4 R groups in the aromatic or non-aromatic moiety. ９ It may be substituted with the base, where R ９ However, each is independent of C １ -C ６ Alkyl, C １ -C ６ Alkoxy, C ３ -C ６ Cycloalkyl, cyano, hydroxy, oxo, halogen, halo C １ -C ３ Alkyl, hydroxy C １ -C ６ Alkyl, amino, mono, or di (C) １ -C ６ Alkyl)amino, or phenyl or phenyl (C) １ -C ３ Alkanoyl) (where each phenyl is C １ -C ３ Alkyl, C １ -C ３ Alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C) １ -C ３ It is alkyl (may be substituted with amino), The compound according to claim 34.

38. R ７ and R ８ However, together with the nitrogen atoms to which they are bonded, they form a 3-7 membered monocyclic heterocyclyl group. The heterocyclyl group, together with carbon atoms from a monocyclic heterocyclyl group and further carbon or heteroatoms, forms a spirocyclic ring system having a total of up to 10 ring members, where the spirocyclic ring system has 1 to 4 R ９ It may be substituted with the base, Here R ９ Each of them is independent of C １ -C ６ Alkyl, C １ -C ６ Alkoxy, C ３ -C ６ Cycloalkyl, cyano, hydroxy, oxo, halogen, halo C １ -C ３ Alkyl, hydroxy C １ -C ６ Alkyl, amino, mono, or di (C) １ -C ６ Alkyl)amino, or phenyl or phenyl (C) １ -C ３ Alkanoyl) (where each phenyl is C １ -C ３ Alkyl, C １ -C ３ Alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C) １ -C ３ It is alkyl (may be substituted with amino), The compound according to claim 34.

39. R ７ and R ８ However, together with the nitrogen atoms to which they are bonded, they form piperidinyl, piperazinyl, or morpholinyl groups, each of which contains 1 to 4 R atoms. ９ It may be substituted with the base, where R ９ Each of them is independent of C １ -C ６ Alkyl, C １ -C ６ Alkoxy, C ３ -C ６ Cycloalkyl, cyano, hydroxy, oxo, halogen, halo C １ -C ３ Alkyl, hydroxy C １ -C ６ Alkyl, amino, mono, or di (C) １ -C ６ Alkyl)amino, or phenyl or phenyl (C) １ -C ３ Alkanoyl) (where each phenyl is C １ -C ３ Alkyl, C １ -C ３ Alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C) １ -C ３ The compound according to claim 34, which may be substituted with alkyl(amino) groups.

40. R ７ and R ８ However, together with the nitrogen atoms to which they are bonded, they form piperidinyl, piperazinyl, or morpholinyl groups, each of which contains 1 to 4 R atoms. ９ It may be substituted with the base, where R ９ However, each is independent of C １ -C ３ Alkyl, C １ -C ３ Alkoxy, C ３ -C ６ Cycloalkyl, cyano, hydroxy, oxo, halogen, halo C １ -C ３ Alkyl, hydroxy C １ -C ３ Alkyl, amino, or mono or di (C) １ -C ３ The compound according to claim 34, wherein it is an alkyl)amino.

41. R ７ and R ８ However, together with the nitrogen atoms to which they are bonded, they form piperidinyl, piperazinyl, or morpholinyl groups, each of which contains 1 to 4 R atoms. ９ It may be substituted with the base, where R ９ The compound according to claim 34, wherein each is independently methyl, ethyl, methoxy, ethoxy, cyano, fluoro, chloro, trifluoromethyl, cyclopropyl, or cyclopropylmethyl.

42. Formula (II) or (III): 【Chemistry 2】 [wherein n is 0, 1, 2, 3 or 4; m is 0, 1, 2, or 3. The compound according to claim 1, which is a compound represented by [the formula shown].

43. Equation (II-A): 【Transformation 3】 The compound according to claim 42, as shown by [the symbol].

44. Equation (III-A): 【Chemistry 4】 The compound according to claim 42, as shown by [the symbol].

45. R １ However, H, C １ -C ３ Alkyl, or C ３ -C ６ It is a cycloalkyl; R １２ However, each is independent of C １ -C ４ Alkyl; -OR Ａ , -C(O)OR Ａ , (C １ -C ３ Alkyl)-OR Ａ , -C(O)N(R Ａ ) ２ cyano or halogen; R Ａ However, each is independent of H and C. １ -C ６ Alkyl, or C ３ -C ６ It is a cycloalkyl; R ３ C １ -C ３ Alkyl or C ３ -C ６ It is a cycloalkyl; R ４ However, H, C １ -C ３ Alkyl, C ３ -C ６ A cycloalkyl, cyano, or halo, where each C １ -C ３ The alkyl group may be substituted with 1 to 5 halo groups. The compound according to any one of claims 42 to 44.

46. R ３ C １ -C ３ The compound according to any one of claims 42 to 45, wherein it is alkyl.

47. R ３ The compound according to any one of claims 42 to 45, wherein is methyl.

48. R ４ H, C １ -C ３ The compound according to any one of claims 42 to 47, wherein it is alkyl, C3-C4 cycloalkyl, or cyano.

49. R ７ is hydrogen, R ８ is hydrogen, C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, or C ３ -C ６ Cycloalkyl (C １ -C ３ A compound according to any one of claims 42 to 47, representing an alkyl group.

50. R ５Ａ NR ７ R ８ Represents R ７ and R ８ However, together with the nitrogen atoms they bond to, they form ring Q, and ring Q is C １ -C ６ A compound according to any one of claims 42 to 47, which is a heterocycline.

51. R ５Ａ NR ７ R ８ Represents R ７ and R ８ However, together with the nitrogen atoms to which they are bonded, they form ring Q, and ring Q is aziridinyl, azetidinyl, pyrrolidinyl, piperazinyl, morpholinyl, piperidinyl, or azepanyl, each of which has 1 to 2 R ９ It may be substituted with the base, where R ９ However, each is independent of C １ -C ６ Alkyl, C １ -C ６ Alkoxy, C ３ -C ６ Cycloalkyl, cyano, hydroxy, oxo, halogen, halo C １ -C ３ Alkyl, hydroxy C １ -C ６ Alkyl, amino, mono, or di (C) １ -C ６ Alkyl)amino, phenyl, 5-7 membered heterocyclyl, or 5-6 membered heteroaryl, where each phenyl, 5-7 membered heterocyclyl, and 5-6 membered heteroaryl has 1-4 C １ -C ３ Alkyl, C １ -C ３ Alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C) １ -C ３ The compound according to any one of claims 42 to 47, which may be substituted with alkyl)amino.

52. R ５Ａ NR ７ R ８ Represents R ７ and R ８ The compound according to any one of claims 42 to 47, wherein, together with the nitrogen to which they are bonded, they form a ring Q, and ring Q is azilidinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or azepanyl, each of which may be substituted with one, two, three, or four halogens.

53. R ５Ａ NR ７ R ８ Represents R ７ and R ８ However, together with the nitrogen atoms to which they are bonded, they form a ring Q, which is a 5-6 member monocyclic heterocyclyl group condensed to an aromatic or non-aromatic ring containing 3-6 ring members, of which 1 or 2 may be nitrogen and the rest may be carbon, and the condensed ring system has 1-4 R atoms on any of the rings. ９ It may be substituted with the base, where R ９ However, each is independent of C １ -C ６ Alkyl, C １ -C ６ Alkoxy, C ３ -C ６ Cycloalkyl, cyano, hydroxy, oxo, halogen, halo C １ -C ３ Alkyl, hydroxy C １ -C ６ Alkyl, amino, or mono or di (C) １ -C ６ The compound according to any one of claims 42 to 47, wherein it is an alkyl)amino compound.

54. R ５Ａ NR ７ R ８ Represents R ７ and R ８ These, together with the nitrogen atoms they bond to, form a ring Q, where ring Q is given by formula: 【Transformation 5】 [In the formula, Each ring A is either a 3- to 6-membered carbocyclic ring or a 3- to 6-membered heterocyclic ring; m is 0, 1, 2, 3, or 4; n is 0, 1, or 2; p and r are independently 1 or 2, provided that p and r together are 2 or 3; R １０ and R １１ Each of them is independent of C １ -C ６ Alkyl, C １ -C ６ Alkoxy, halogen, cyano, hydroxy, hydroxy C １ -C ６ Alkyl, amino, mono, or di(C) １ -C ６ Alkyl)amino, C ３ -C ６ A cycloalkyl, phenyl, or 5-6 membered heteroaryl, where each cycloalkyl, phenyl, and heteroaryl is composed of 1-3 halogens, hydroxyls, and C atoms. １ -C ３ Alkyl, C １ -C ３ Alkoxy, cyano, amino, or mono or di(C) １ -C ３ (May be substituted with alkylamino compounds) The compound according to any one of claims 42 to 47, wherein the group is represented by .

55. R ７ and R ８ However, together with the nitrogen atoms to which they are bonded, they form piperidinyl, piperazinyl, or morpholinyl groups, each of which contains 1 to 4 R atoms. ９ It may be substituted with the base, where R ９ Each of them is independent of C １ -C ６ Alkyl, C １ -C ６ Alkoxy, C ３ -C ６ Cycloalkyl, cyano, hydroxy, oxo, halogen, halo C １ -C ３ Alkyl, hydroxy C １ -C ６ Alkyl, amino, mono, or di (C) １ -C ６ Alkyl)amino, or phenyl or phenyl (C) １ -C ３ Alkanoyl) (where each phenyl is C １ -C ３ Alkyl, C １ -C ３ Alkoxy, halogen, hydroxy, cyano, amino, or mono or di(C) １ -C ３ The compound according to any one of claims 42 to 47, wherein it is alkyl (which may be substituted with amino).

56. R ７ and R ８ However, together with the nitrogen atoms to which they are bonded, they form piperidinyl, piperazinyl, or morpholinyl groups, each of which contains 1 to 4 R atoms. ９ It may be substituted with the base, where R ９ However, each is independent of C １ -C ３ Alkyl, C １ -C ３ Alkoxy, C ３ -C ６ Cycloalkyl, cyano, hydroxy, oxo, halogen, halo C １ -C ３ Alkyl, hydroxy C １ -C ３ Alkyl, amino, or mono or di (C) １ -C ３ The compound according to any one of claims 42 to 47, wherein it is an alkyl)amino.

57. R ７ and R ８ However, together with the nitrogen atoms to which they are bonded, they form piperidinyl, piperazinyl, or morpholinyl groups, each of which contains 1 to 4 R atoms. ９ It may be substituted with the base, where R ９ The compound according to any one of claims 42 to 47, wherein each is independently methyl, ethyl, methoxy, ethoxy, cyano, fluoro, chloro, trifluoromethyl, cyclopropyl, or cyclopropylmethyl.

58. Formula (IV): 【Transformation 6】 [In the formula: R １ H, C １ -C ３ Alkyl, or C ３ -C ６ It is a cycloalkyl; R ２ R is a phenyl or 5-6 membered heteroaryl group, where phenyl and heteroaryl each have 1-5 R １２ It may be replaced as desired; R １２ Each of them is independent of C １ -C ４ Alkyl, -OR Ａ , -C(O)OR Ａ , (C １ -C ３ Alkyl)-OR Ａ , -C(O)N(R Ａ ) ２ cyano or halogen; R Ａ These are H and C, respectively, independently. １ -C ６ Alkyl, or C ３ -C ６ It is a cycloalkyl; R ３ C may be substituted, polysubstituted, or oversubstituted with fluoropolymers. １ -C ３ Alkyl, C ３ -C ６ Cycloalkyl, C １ -C ３ Alkenil, C ２ -C ３ Alkinyl, or C ５ -C ６ It is a cycloalkenyl; R ４ H, halogen, C １ -C ３ Alkyl, C ３ -C ６ Cycloalkyl, C １ -C ３ Alkenil, C ２ -C ３ Alkinyl or C ５ -C ６ A cycloalkenyl or cyano, where C １ -C ３ Alkyl and C ３ -C ６ Each cycloalkyl group may be substituted with 1 to 5 halo groups; R ６ and R ６Ａ H or C １ -C ６ Represents alkyl; R ５ C １ -C ２ It is alkyl, cyclopropyl, bromo, chloro, fluoro, cyano, or trifluoromethyl; R ５Ａ NR ７ R ８ , C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, C ３ -C ６ Cycloalkyl (C １ -C ３ This represents an alkyl, phenyl, or 5-6 member heteroaryl group, where C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, C ３ -C ６ Cycloalkyl (C １ -C ３ Alkyl), phenyl, and heteroaryl each contain 1 to 3 halogens, halo(C) １ -C ３ Alkyl), hydroxy, C １ -C ３ Alkyl, C １ -C ３ Alkoxy, cyano, amino, or mono or di(C) １ -C ３ ) It may also be substituted with alkylamino; R ７ is H or C １ -C ３ Represents alkyl; R ８ H, C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, or C ３ -C ６ Cycloalkyl (C １ -C ３ This represents alkyl, where C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, and C ３ -C ６ Cycloalkyl (C １ -C ３ Alkyl) each contains 1 to 3 halogens, halo(C) １ -C ３ Alkyl), hydroxy, C １ -C ３ Alkyl, C １ -C ３ Alkoxy, cyano, amino, or mono or di(C) １ -C ３ ) may be substituted with alkylamino; or R ７ and R ８ These, together with the nitrogen atoms to which they bond, form a ring Q, where ring Q is A 3-8 member monocyclic heterocyclyl group, where the heterocyclyl group contains 3-6 ring members, of which 1 or 2 are nitrogen, oxygen, or sulfur atoms, and the rest are carbon atoms, which may be condensed with an aromatic or non-aromatic ring, or Carbon atoms from a monocyclic heterocyclyl group, together with further carbons and heteroatoms, form a spirocyclic ring system having a total of up to 10 ring members, where the ring members are carbon and one or two heteroatoms selected from nitrogen, sulfur, and oxygen atoms. Here, ring Q has 1 to 4 R in each aromatic or non-aromatic moiety. ９ It may be substituted with the base, where R ９ Each of them is independently (i)C １ -C ６ Alkyl, (ii) C １ -C ６ Alkoxy, (iii) C ３ -C ６ Cycloalkyl, (iv) cyano, (ii) hydroxy, (v) oxo, (vi) halogen, (vii) halo C １ -C ３ Alkyl, (viiii)hydroxy C １ -C ６ Alkyl, (ix)amino, (x)mono or di-(C) １ -C ６ (Alkyl)amino, (xi) 1 or 2 C １ -C ３ Alkyl, C １ -C ３ Alkoxy, C ３ -C ６ Cycloalkyl, cyano, hydroxy, oxo, halogen, halo C １ -C ３ Alkyl, hydroxy C １ -C ３ Alkyl, amino, or mono or di (C) １ -C ６ C may be substituted with alkyl)amino ２ -C ６ Alcanoil (Here, C on Alcanoil) １ -C ３ Alkyl or C ３ -C ６ The cycloalkyl group may be substituted with a halogen, hydroxyl, or amino group, respectively. (xii)C ３ -C ６ Cycloalkyloxy, or (xiiii)phenyl, phenyl (C １ -C ３ Alkanoyl), 5-7 membered heterocyclyl, or 5-6 membered heteroaryl (where each phenyl, 5-7 membered heterocyclyl, and 5-6 membered heteroaryl has 1-4 C １ -C ３ Alkyl, C １ -C ３ Alkoxy, halogen, hydroxy, cyano, oxo, amino, or mono or di(C) １ -C ３ [It may be substituted with alkyl (amino)] Compounds represented by , or their pharmaceutically acceptable salts, prodrugs, solvates, hydrates, isomers, deuterated forms, or tautomers.

59. Equation (IV-A): 【Transformation 7】 [In the formula: R １ H, C １ -C ３ Alkyl, or C ３ -C ６ It is a cycloalkyl; R ２ R is a phenyl or 5-6 membered heteroaryl group, where phenyl and heteroaryl each have 1-5 R １２ It may be replaced as desired; R １２ Each of them is independent of C １ -C ４ Alkyl, -OR Ａ , -C(O)OR Ａ , (C １ -C ３ Alkyl)-OR Ａ , -C(O)N(R Ａ ) ２ cyano or halogen; R Ａ These are H and C, respectively, independently. １ -C ６ Alkyl, or C ３ -C ６ It is a cycloalkyl; R ３ C may be substituted, polysubstituted, or oversubstituted with fluoropolymers. １ -C ３ Alkyl, C ３ -C ６ Cycloalkyl, C １ -C ３ Alkenil, C ２ -C ３ Alkinyl, or C ５ -C ６ It is a cycloalkenyl; R ４ H, halogen, C １ -C ３ Alkyl, C ３ -C ６ Cycloalkyl, C １ -C ３ Alkenil, C ２ -C ３ Alkinyl, or C ５ -C ６ A cycloalkenyl or cyano, where C １ -C ３ Alkyl and C ３ -C ６ Each cycloalkyl group may be substituted with 1 to 5 halo groups; R ６ and R ６Ａ H or C １ -C ６ Represents alkyl; R ５Ａ NR ７ R ８ , C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, C ３ -C ６ Cycloalkyl (C １ -C ３ This represents an alkyl, phenyl, or 5-6 member heteroaryl group, where C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, C ３ -C ６ Cycloalkyl (C １ -C ３ Alkyl, phenyl, and heteroaryl compounds each contain 1 to 3 halogens, halo(C) １ -C ３ Alkyl), hydroxy, C １ -C ３ Alkyl, C １ -C ３ Alkoxy, cyano, amino, or mono or di(C) １ -C ３ ) It may also be substituted with alkylamino; R ７ is H or C １ -C ３ Represents alkyl; R ８ represents H, C １ -C ６ alkyl, C ３ -C ６ cycloalkyl, or C ３ -C ６ cycloalkyl (C １ -C ３ alkyl), where C １ -C ６ alkyl, C ３ -C ６ cycloalkyl, and C ３ -C ６ cycloalkyl (C １ -C ３ alkyl) may each be substituted with 1 to 3 halogens, halo(C １ -C ３ alkyl), hydroxy, C １ -C ３ alkyl, C １ -C ３ alkoxy, cyano, amino, or mono- or di(C １ -C ３ alkyl)amino; or R ７ and R ８ These, together with the nitrogen atoms to which they bond, form a ring Q, where ring Q is A 3-8 member monocyclic heterocyclyl group, where the heterocyclyl group contains 3-6 ring members, of which 1 or 2 are nitrogen, oxygen, or sulfur atoms, and the rest are carbon atoms, which may be condensed with an aromatic or non-aromatic ring, or Carbon atoms from a monocyclic heterocyclyl group, along with further carbons and heteroatoms, form a spirocyclic ring system having a total of up to 10 ring members, where the ring members are carbon or heteroatoms selected from one or two nitrogen, sulfur, and oxygen atoms. Here, ring Q has 1 to 4 R in each aromatic or non-aromatic moiety. ９ It may be substituted with the base, where R ９ Each of them is independently (i)C １ -C ６ Alkyl, (ii) C １ -C ６ Alkoxy, (iii) C ３ -C ６ Cycloalkyl, (iv) cyano, (ii) hydroxy, (v) oxo, (vi) halogen, (vii) halo C １ -C ３ Alkyl, (viiii)hydroxy C １ -C ６ Alkyl, (ix)amino, (x)mono or di-(C) １ -C ６ (Alkyl)amino, (xi) 1 or 2 C １ -C ３ Alkyl, C １ -C ３ Alkoxy, C ３ -C ６ Cycloalkyl, cyano, hydroxy, oxo, halogen, halo C １ -C ３ Alkyl, hydroxy C １ -C ３ Alkyl, amino, or mono or di (C) １ -C ６ C may be substituted with alkyl)amino ２ -C ６ Alkanoyl (where C on Alkanoyl) １ -C ３ Alkyl or C ３ -C ６ The cycloalkyl group may be substituted with a halogen, hydroxyl, or amino group, respectively. (xii)C ３ -C ６ Cycloalkyloxy, or (xiiii)phenyl, phenyl (C １ -C ３ Alkanoyl), 5-7 membered heterocyclyl, or 5-6 membered heteroaryl (where each phenyl, 5-7 membered heterocyclyl, and 5-6 membered heteroaryl contains 1-4 C １ -C ３ Alkyl, C １ -C ３ Alkoxy, halogen, hydroxy, cyano, oxo, amino, or mono or di(C) １ -C ３ [It may be substituted with alkyl (amino)] Compounds represented by , or their pharmaceutically acceptable salts, prodrugs, solvates, hydrates, isomers, deuterated forms, or tautomers.

60. Formula (IV-B): 【Transformation 8】 [In the formula: R １ H, C １ -C ３ Alkyl, or C ３ -C ６ It is a cycloalkyl; R ２ R is a phenyl or 5-6 membered heteroaryl group, where phenyl and heteroaryl each have 1-5 R １２ It may be replaced with; R １２ each independently is C １ -C ４ -alkyl, -OR Ａ -C(O)OR Ａ (C １ -C ３ -alkyl)-OR Ａ -C(O)N(R Ａ ) ２ cyano, or halogen; R Ａ These are H and C, respectively, independently. １ -C ６ Alkyl, or C ３ -C ６ It is a cycloalkyl; R ３ C may be substituted, polysubstituted, or oversubstituted with fluoropolymers. １ -C ３ Alkyl, C ３ -C ６ Cycloalkyl, C １ -C ３ Alkenil, C ２ -C ３ Alkinyl, or C ５ -C ６ It is a cycloalkenyl; R ４ H, halogen, C １ -C ３ Alkyl, C ３ -C ６ Cycloalkyl, C １ -C ３ Alkenil, C ２ -C ３ Alkinyl, or C ５ -C ６ A cycloalkenyl or cyano, where C １ -C ３ Alkyl and C ３ -C ６ Each cycloalkyl group may be substituted with 1 to 5 halo groups; R ６ and R ６Ａ H or C １ -C ６ Represents alkyl; R ５Ａ NR ７ R ８ , C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, C ３ -C ６ Cycloalkyl (C １ -C ３ This represents an alkyl, phenyl, or 5-6 member heteroaryl group, where C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, C ３ -C ６ Cycloalkyl (C １ -C ３ Alkyl), phenyl, and heteroaryl each contain 1 to 3 halogens, halo(C) １ -C ３ Alkyl), hydroxy, C １ -C ３ Alkyl, C １ -C ３ Alkoxy, cyano, amino, or mono or di(C) １ -C ３ ) It may also be substituted with alkylamino; R ７ is H or C １ -C ３ Represents alkyl; R ８ H, C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, or C ３ -C ６ Cycloalkyl (C １ -C ３ This represents alkyl, where C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl and C ３ -C ６ Cycloalkyl (C １ -C ３ Alkyl) each contains 1 to 3 halogens, halo(C) １ -C ３ Alkyl), hydroxy, C １ -C ３ Alkyl, C １ -C ３ Alkoxy, cyano, amino, or mono or di(C) １ -C ３ ) may be substituted with alkylamino; or R ７ and R ８ These, together with the nitrogen atoms to which they bond, form a ring Q, where ring Q is A 3-8 member monocyclic heterocyclyl group, where the heterocyclyl group contains 3-6 ring members, of which 1 or 2 are nitrogen, oxygen, or sulfur atoms, and the rest are carbon, which may be condensed with an aromatic or non-aromatic ring, or Carbon atoms from a monocyclic heterocyclyl group, together with further carbon or heteroatoms, form a spirocyclic ring system having a total of up to 10 ring members, where the ring members are carbon or heteroatoms selected from one or two nitrogen, sulfur, and oxygen atoms. Here, ring Q has 1 to 4 R in each aromatic or non-aromatic moiety. ９ It may be substituted with the base, where R ９ Each of them is independently (i)C １ -C ６ Alkyl, (ii) C １ -C ６ Alkoxy, (iii) C ３ -C ６ Cycloalkyl, (iv) cyano, (ii) hydroxy, (v) oxo, (vi) halogen, (vii) halo C １ -C ３ Alkyl, (viiii)hydroxy C １ -C ６ Alkyl, (ix)amino, (x)mono or di-(C) １ -C ６ (Alkyl)amino, (xi) 1 or 2 C １ -C ３ Alkyl, C １ -C ３ Alkoxy, C ３ -C ６ Cycloalkyl, cyano, hydroxy, oxo, halogen, halo C １ -C ３ Alkyl, hydroxy C １ -C ３ Alkyl, amino, or mono or di (C) １ -C ６ C may be substituted with alkyl)amino ２ -C ６ Alkanoyl (where C on Alkanoyl) １ -C ３ Alkyl or C ３ -C ６ The cycloalkyl group may be substituted with a halogen, hydroxyl, or amino group, respectively. (xii)C ３ -C ６ Cycloalkyloxy, or (xiiii)phenyl, phenyl (C １ -C ３ Alkanoyl), 5-7 membered heterocyclyl, or 5-6 membered heteroaryl (where each phenyl, 5-7 membered heterocyclyl, and 5-6 membered heteroaryl has 1-4 C １ -C ３ Alkyl, C １ -C ３ Alkoxy, halogen, hydroxy, cyano, oxo, amino, or mono or di(C) １ -C ３ [It may be substituted with alkyl (amino)] Compounds represented by , or their pharmaceutically acceptable salts, prodrugs, solvates, hydrates, isomers, deuterated forms, or tautomers.

61. Formula (IV-C): 【Chemistry 9】 [In the formula: R １ H, C １ -C ３ Alkyl, or C ３ -C ６ It is a cycloalkyl; R ２ R is a phenyl or 5-6 membered heteroaryl group, where phenyl and heteroaryl each have 1-5 R １２ It may be replaced with; R １２ Each of them is independent of C １ -C ４ Alkyl, -OR Ａ , -C(O)OR Ａ , (C １ -C ３ Alkyl)-OR Ａ , -C(O)N(R Ａ ) ２ cyano or halogen; R Ａ These are H and C, respectively, independently. １ -C ６ Alkyl, or C ３ -C ６ It is a cycloalkyl; R ３ C may be substituted, polysubstituted, or oversubstituted with fluoropolymers. １ -C ３ Alkyl, C ３ -C ６ Cycloalkyl, C １ -C ３ Alkenil, C ２ -C ３ Alkinyl, or C ５ -C ６ It is a cycloalkenyl; R ４ H, halogen, C １ -C ３ Alkyl, C ３ -C ６ Cycloalkyl, C １ -C ３ Alkenil, C ２ -C ３ Alkinyl, or C ５ -C ６ It is a cycloalkenyl or cyano, where C １ -C ３ Alkyl and C ３ -C ６ Each cycloalkyl group may be substituted with 1 to 5 halo groups; R ６ and R ６Ａ H or C １ -C ６ Represents alkyl; R ５Ａ NR ７ R ８ , C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, C ３ -C ６ Cycloalkyl (C １ -C ３ This represents an alkyl, phenyl, or 5-6 member heteroaryl group, where C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, C ３ -C ６ Cycloalkyl (C １ -C ３ Alkyl, phenyl, and heteroaryl compounds each contain 1 to 3 halogens, halo(C) １ -C ３ Alkyl), hydroxy, C １ -C ３ Alkyl, C １ -C ３ Alkoxy, cyano, amino, or mono or di(C) １ -C ３ ) It may also be substituted with alkylamino; R ７ is H or C １ -C ３ Represents alkyl; R ８ H, C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, or C ３ -C ６ Cycloalkyl (C １ -C ３ This represents alkyl, where C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl and C ３ -C ６ Cycloalkyl (C １ -C ３ Alkyl) each contains 1 to 3 halogens, halo(C) １ -C ３ Alkyl), hydroxy, C １ -C ３ Alkyl, C １ -C ３ Alkoxy, cyano, amino, or mono or di(C) １ -C ３ ) may be substituted with alkylamino; or R ７ and R ８ These, together with the nitrogen atoms to which they bond, form a ring Q, where ring Q is A 3-8 member monocyclic heterocyclyl group, where the heterocyclyl group contains 3-6 ring members, of which 1 or 2 are nitrogen, oxygen, or sulfur atoms, and the rest are carbon atoms, which may be condensed with an aromatic or non-aromatic ring, or Carbon atoms from a monocyclic heterocyclyl group, along with further carbons and heteroatoms, form a spirocyclic ring system having a total of up to 10 ring members, where the ring members are carbon or heteroatoms selected from one or two nitrogen, sulfur, and oxygen atoms. Here, ring Q has 1 to 4 R in each aromatic or non-aromatic moiety. ９ It may be substituted with the base, where R ９ Each of them is independently (i)C １ -C ６ Alkyl, (ii) C １ -C ６ Alkoxy, (iii) C ３ -C ６ Cycloalkyl, (iv) cyano, (ii) hydroxy, (v) oxo, (vi) halogen, (vii) halo C １ -C ３ Alkyl, (viiii)hydroxy C １ -C ６ Alkyl, (ix)amino, (x)mono or di-(C) １ -C ６ (Alkyl)amino, (xi) 1 or 2 C １ -C ３ Alkyl, C １ -C ３ Alkoxy, C ３ -C ６ Cycloalkyl, cyano, hydroxy, oxo, halogen, halo C １ -C ３ Alkyl, hydroxy C １ -C ３ Alkyl, amino, or mono or di (C) １ -C ６ C may be substituted with alkyl)amino ２ -C ６ Alkanoyl (where C on Alkanoyl) １ -C ３ Alkyl or C ３ -C ６ The cycloalkyl group may be substituted with a halogen, hydroxyl, or amino group), (xi)C ３ -C ６ Cycloalkyloxy, or (xiiii)phenyl, phenyl (C １ -C ３ Alkanoyl), 5-7 membered heterocyclyl, or 5-6 membered heteroaryl (where each phenyl, 5-7 membered heterocyclyl, and 5-6 membered heteroaryl has 1-4 C １ -C ３ Alkyl, C １ -C ３ Alkoxy, halogen, hydroxy, cyano, oxo, amino, or mono or di(C) １ -C ３ [It may be substituted with alkyl (amino)] Compounds represented by , or their pharmaceutically acceptable salts, prodrugs, solvates, hydrates, isomers, deuterated forms, or tautomers.

62. Formula (IV-D): 【Chemistry 10】 [In the formula: R １ H, C １ -C ３ Alkyl, or C ３ -C ６ It is a cycloalkyl; R ２ R is a phenyl or 5-6 membered heteroaryl group, where phenyl and heteroaryl each have 1-5 R １２ It may be replaced with; R １２ Each of them is independent of C １ -C ４ Alkyl, -OR Ａ , -C(O)OR Ａ , (C １ -C ３ Alkyl)-OR Ａ , -C(O)N(R Ａ ) ２ cyano or halogen; R Ａ These are H and C, respectively, independently. １ -C ６ Alkyl, or C ３ -C ６ It is a cycloalkyl; R ３ C may be substituted, polysubstituted, or oversubstituted with fluoropolymers. １ -C ３ Alkyl, C ３ -C ６ Cycloalkyl, C １ -C ３ Alkenil, C ２ -C ３ Alkinyl, or C ５ -C ６ It is a cycloalkenyl; R ４ H, halogen, C １ -C ３ Alkyl, C ３ -C ６ Cycloalkyl, C １ -C ３ Alkenil, C ２ -C ３ Alkinyl, or C ５ -C ６ A cycloalkenyl or cyano, where C １ -C ３ Alkyl and C ３ -C ６ Each cycloalkyl group may be substituted with 1 to 5 halo groups; R ６ and R ６Ａ H or C １ -C ６ Represents alkyl; R ５Ａ NR ７ R ８ , C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, C ３ -C ６ Cycloalkyl (C １ -C ３ This represents an alkyl, phenyl, or 5-6 member heteroaryl group, where C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, C ３ -C ６ Cycloalkyl (C １ -C ３ Alkyl), phenyl, and heteroaryl each contain 1 to 3 halogens, halo(C) １ -C ３ Alkyl), hydroxy, C １ -C ３ Alkyl, C １ -C ３ Alkoxy, cyano, amino, or mono or di(C) １ -C ３ ) It may also be substituted with alkylamino; R ７ is H or C １ -C ３ Represents alkyl; R ８ H, C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, or C ３ -C ６ Cycloalkyl (C １ -C ３ This represents alkyl, where C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl and C ３ -C ６ Cycloalkyl (C １ -C ３ Alkyl) each contains 1 to 3 halogens, halo(C) １ -C ３ Alkyl), hydroxy, C １ -C ３ Alkyl, C １ -C ３ Alkoxy, cyano, amino, or mono or di(C) １ -C ３ ) may be substituted with alkylamino; or R ７ and R ８ These, together with the nitrogen atoms to which they bond, form a ring Q, where ring Q is A 3-8 member monocyclic heterocyclyl group, where the heterocyclyl group contains 3-6 ring members, of which 1 or 2 are nitrogen, oxygen, or sulfur atoms, and the rest are carbon atoms, which may be condensed with an aromatic or non-aromatic ring, or Carbon atoms from a monocyclic heterocyclyl group, along with further carbons and heteroatoms, form a spirocyclic ring system having a total of up to 10 ring members, where the ring members are carbon or heteroatoms selected from one or two nitrogen, sulfur, and oxygen atoms. Here, ring Q has 1 to 4 R in each aromatic or non-aromatic moiety. ９ It may be substituted with the base, where R ９ Each of them is independently (i)C １ -C ６ Alkyl, (ii) C １ -C ６ Alkoxy, (iii) C ３ -C ６ Cycloalkyl, (iv) cyano, (ii) hydroxy, (v) oxo, (vi) halogen, (vii) halo C １ -C ３ Alkyl, (viiii)hydroxy C １ -C ６ Alkyl, (ix)amino, (x)mono or di-(C) １ -C ６ (Alkyl)amino, (xi) 1 or 2 C １ -C ３ Alkyl, C １ -C ３ Alkoxy, C ３ -C ６ Cycloalkyl, cyano, hydroxy, oxo, halogen, halo C １ -C ３ Alkyl, hydroxy C １ -C ３ Alkyl, amino, or mono or di (C) １ -C ６ C may be substituted with alkyl)amino ２ -C ６ Alkanoyl (where C on Alkanoyl) １ -C ３ Alkyl or C ３ -C ６ The cycloalkyl group may be substituted with a halogen, hydroxyl, or amino group, respectively. (xii)C ３ -C ６ Cycloalkyloxy, or (xiiii)phenyl, phenyl (C １ -C ３ Alkanoyl), 5-7 membered heterocyclyl, or 5-6 membered heteroaryl (where each phenyl, 5-7 membered heterocyclyl, and 5-6 membered heteroaryl has 1-4 C １ -C ３ Alkyl, C １ -C ３ Alkoxy, halogen, hydroxy, cyano, oxo, amino, or mono or di(C) １ -C ３ [It may be substituted with alkyl (amino)] Compounds represented by , or their pharmaceutically acceptable salts, prodrugs, solvates, hydrates, isomers, deuterated forms, or tautomers.

63. Equation (IV-E): 【Chemistry 11】 [In the formula: R １ H, C １ -C ３ Alkyl, or C ３ -C ６ It is a cycloalkyl; R ２ R is a phenyl or 5-6 membered heteroaryl group, where phenyl and heteroaryl each have 1-5 R １２ It may be replaced as desired; R １２ Each of them is independent of C １ -C ４ Alkyl, -OR Ａ , -C(O)OR Ａ , (C １ -C ３ Alkyl)-OR Ａ , -C(O)N(R Ａ ) ２ cyano or halogen; R Ａ These are H and C, respectively, independently. １ -C ６ Alkyl, or C ３ -C ６ It is a cycloalkyl; R ３ C may be substituted, polysubstituted, or oversubstituted with fluoropolymers. １ -C ３ Alkyl, C ３ -C ６ Cycloalkyl, C １ -C ３ Alkenil, C ２ -C ３ Alkinyl, or C ５ -C ６ It is a cycloalkenyl; R ４ H, halogen, C １ -C ３ Alkyl, C ３ -C ６ Cycloalkyl, C １ -C ３ Alkenil, C ２ -C ３ Alkinyl, or C ５ -C ６ A cycloalkenyl or cyano, where C １ -C ３ Alkyl and C ３ -C ６ Each cycloalkyl group may be substituted with 1 to 5 halo groups; RH stands for bromo, chloro, or fluoro. R ６ and R ６Ａ H or C １ -C ６ Represents alkyl; R ５Ａ NR ７ R ８ , C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, C ３ -C ６ Cycloalkyl (C １ -C ３ This represents an alkyl, phenyl, or 5-6 member heteroaryl group, where C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, C ３ -C ６ Cycloalkyl (C １ -C ３ Alkyl, phenyl, and heteroaryl compounds each contain 1 to 3 halogens, halo(C) １ -C ３ Alkyl), hydroxy, C １ -C ３ Alkyl, C １ -C ３ Alkoxy, cyano, amino, or mono or di(C) １ -C ３ ) It may also be substituted with alkylamino; R ７ is H or C １ -C ３ Represents alkyl; R ８ H, C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, or C ３ -C ６ Cycloalkyl (C １ -C ３ This represents alkyl, where C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, and C ３ -C ６ Cycloalkyl (C １ -C ３ Alkyl) each contains 1 to 3 halogens, halo(C) １ -C ３ Alkyl), hydroxy, C １ -C ３ Alkyl, C １ -C ３ Alkoxy, cyano, amino, or mono or di(C) １ -C ３ ) may be substituted with alkylamino; or R ７ and R ８ These, together with the nitrogen atoms to which they bond, form a ring Q, where ring Q is A 3-8 member monocyclic heterocyclyl group, where the heterocyclyl group contains 3-6 ring members, of which 1 or 2 are nitrogen, oxygen, or sulfur atoms, and the rest are carbon, which may be condensed with an aromatic or non-aromatic ring, or Carbon atoms from a monocyclic heterocyclyl group, along with further carbons and heteroatoms, form a spirocyclic ring system having a total of up to 10 ring members, where the ring members are carbon or heteroatoms selected from one or two nitrogen, sulfur, and oxygen atoms. Here, ring Q has 1 to 4 R in each aromatic or non-aromatic moiety. ９ It may be substituted with the base, where R ９ Each of them is independently (i)C １ -C ６ Alkyl, (ii) C １ -C ６ Alkoxy, (iii) C ３ -C ６ Cycloalkyl, (iv) cyano, (ii) hydroxy, (v) oxo, (vi) halogen, (vii) halo C １ -C ３ Alkyl, (viiii)hydroxy C １ -C ６ Alkyl, (ix)amino, (x)mono or di-(C) １ -C ６ (Alkyl)amino, (xi) 1 or 2 C １ -C ３ Alkyl, C １ -C ３ Alkoxy, C ３ -C ６ Cycloalkyl, cyano, hydroxy, oxo, halogen, halo C １ -C ３ Alkyl, hydroxy C １ -C ３ Alkyl, amino, or mono or di (C) １ -C ６ C may be substituted with alkyl)amino ２ -C ６ Alkanoyl (where C on Alkanoyl) １ -C ３ Alkyl or C ３ -C ６ The cycloalkyl group may be substituted with a halogen, hydroxyl, or amino group), (xi)C ３ -C ６ Cycloalkyloxy, or (xiiii)phenyl, phenyl (C １ -C ３ Alkanoyl), 5-7 membered heterocyclyl, or 5-6 membered heteroaryl (where each phenyl, 5-7 membered heterocyclyl, and 5-6 membered heteroaryl has 1-4 C １ -C ３ Alkyl, C １ -C ３ Alkoxy, halogen, hydroxy, cyano, oxo, amino, or mono or di(C) １ -C ３ [It may be substituted with alkyl (amino)] Compounds represented by , or their pharmaceutically acceptable salts, prodrugs, solvates, hydrates, isomers, deuterated forms, or tautomers.

64. 2-((1-(2-cyano-7-methyl-3-(piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-((1-(2-cyano-3-(isoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-3-(isoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-3-(6,6-difluoro-3-azabicyclo[3.1.1]heptan-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-3-(6,6-difluoro-2-azabicyclo[2.2.1]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-3-(3,3-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-3-(((2,2-difluorocyclopropyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-7-methyl-3-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-3-(1,1-difluoro-5-azaspiro[2,3]hexane-5-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)-6-methylpicolinic acid; 2-((1-(2-cyano-3-((cyclopropylmethyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-7-methyl-3-(3-(trifluoromethyl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-(trifluoromethyl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-3-(6,6-difluoro-3-azabicyclo[3.1.0]hexane-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-3-(4,4-difluoro-6-azaspiro[2.5]octan-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-3-(((1-fluorocyclopropyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-3-(5-fluoroisoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-3-((cyclopropylmethyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-fluoroquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-fluoroquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-((1-(2-cyano-7-fluoro-3-(4-fluoropiperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-((1-(2,7-dicyano-3-(4-fluoropiperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-((1-(2,7-dicyano-3-(4,4-difluoropiperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-((1-(7-chloro-2-cyano-3-(4,4-difluoropiperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-7-cyclopropyl-3-(4,4-difluoropiperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(7-Chloro-2-cyano-3-(4,4-difluoropiperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(3-(4,4-difluoropiperidine-1-yl)-2,7-dimethylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(3-(4,4-difluoropiperidine-1-yl)-2,7-dimethylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-((1-(2-cyano-7-cyclopropyl-3-(4,4-difluoropiperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methoxyquinoxaline-5-yl)ethyl)amino)benzoic acid; 5-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)thiazole-4-carboxylic acid; 2-Chloro-5-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)thiazole-4-carboxylic acid; 2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)thiophene-3-carboxylic acid; 3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)thiophen-2-carboxylic acid; 6-Chloro-3-((1-(2-cyano-7-methyl-3-(1-(trifluoromethyl)-3-azabicyclo[3.1.0]hexane-3-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-3-cyclopropyl-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-3-(3-(difluoromethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-3-(1-(fluoromethyl)-3-azabicyclo[3.1.0]hexane-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyclopropyl-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(3-(4,4-difluoropiperidine-1-yl)-7-methyl-2-(trifluoromethyl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(3-(4,4-difluoropiperidine-1-yl)-7-methyl-2-(trifluoromethyl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-ethylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-Chloro-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-chloro-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 3-((1-(3-(4,4-difluoropiperidine-1-yl)-2,7-dimethylquinoxaline-5-yl)ethyl)amino)-6-methylpicolinic acid; 2-((1-(2-cyano-3-(3,3-dimethylazetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-3-(3,3-dimethylazetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-7-methyl-3-morpholinoxaline-5-yl)ethyl)aminobenzoic acid; 6-Chloro-3-((1-(2-cyano-7-methyl-3-morpholinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-7-methyl-3-(2-oxa-6-azaspiro[3,3]heptan-6-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-7-methyl-3-(2-oxa-6-azaspiro[3,3]heptan-6-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-3-(4,4-dimethylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-3-(4,4-dimethylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-3-(3-methoxy-3-methylazetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-3-(3-methoxy-3-methylazetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-7-methyl-3-(4-methyl-4-(trifluoromethyl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-7-methyl-3-(4-methyl-4-(trifluoromethyl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-3-cyclopropyl-7-methylquinoxaline-5-yl)ethyl)aminobenzoic acid; 2-((1-(2-cyano-7-methyl-3-(pyrrolidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-7-methyl-3-(pyrrolidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-3-(3,3-difluoropyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-3-(3,3-difluoropyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-((1-(2-cyano-3-(3-methoxypyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-3-(3-methoxypyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-3-(((2,2-difluoro-1-methylcyclopropyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-3-(((2,2-difluoro-1-methylcyclopropyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-((1-(2-cyano-3-((3,3-difluorocyclobutyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-3-((3,3-difluorocyclobutyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-3-(4,4-difluoro-3-methylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-3-(4,4-difluoro-3-methylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-3-(3,3-difluoro-4-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-3-(3,3-difluoro-4-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-7-methyl-3-(1,1,2,2-tetrafluoro-6-azaspiro[2.5]octan-6-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-3-(3,4-dihydroisoquinoline-2(1H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-3-(3,4-dihydroisoquinoline-2(1H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-3-(6-cyano-3,4-dihydroisoquinoline-2(1H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-3-(6-cyano-3,4-dihydroisoquinoline-2(1H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-3-(6-fluoro-3,4-dihydroisoquinoline-2(1H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-3-(6-fluoro-3,4-dihydroisoquinoline-2(1H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-((1-(2-cyano-3-(3,4-dihydro-2,7-naphthyridine-2(1H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-3-(4-(2-cyclopropylacetyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-3-(4-(2-cyclopropylacetyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-3-(4-(2-(2,2-difluorocyclopropyl)acetyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-3-(4-(2-(2,2-difluorocyclopropyl)acetyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-3-(1-hydroxy-6-azaspiro[3.5]nonanane-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-3-(1-hydroxy-6-azaspiro[3.5]nonanane-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-7-methyl-3-(3-(1-methyl-1H-pyrazole-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-7-methyl-3-(3-(1-methyl-1H-pyrazole-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-((1-(2-cyano-7-methyl-3-(3-(1-methyl-1H-pyrazole-3-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-((1-(2-cyano-7-methyl-3-(3-(1-methyl-1H-pyrazole-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-7-methyl-3-(3-(1-methyl-1H-pyrazole-3-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-7-methyl-3-(3-(1-methyl-1H-pyrazole-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-((1-(2-cyano-7-methyl-3-(2-oxo-[1,4'-bipiperidine]-1'-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-7-methyl-3-(2-oxo-[1,4'-bipiperidine]-1'-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(2-cyano-3-(4-(ethoxymethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-((1-(2-cyano-3-(4-(ethoxymethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid or a pharmaceutically acceptable salt thereof The compound according to claim 1.

65. (R)-2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (S)-2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(2-cyano-3-(isoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-(((1R)-1-(2-Cyano-3-(6,6-Difluoro-3-azabicyclo[3.1.1]heptan-3-yl)-7-Methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((1S,4S)-5,5-difluoro-2-azabicyclo[2.2.1]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((1R,4R)-5,5-difluoro-2-azabicyclo[2.2.1]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((1R,4S)-6,6-difluoro-2-azabicyclo[2.2.1]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((1S,4R)-6,6-difluoro-2-azabicyclo[2.2.1]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3,3-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((((S)-2,2-difluorocyclopropyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((((R)-2,2-difluorocyclopropyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(1,1-difluoro-5-azaspiro[2,3]hexane-5-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)-6-methylpicolinic acid; (R)-2-((1-(2-cyano-3-((cyclopropylmethyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(3-(trifluoromethyl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-(trifluoromethyl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(6,6-difluoro-3-azabicyclo[3.1.0]hexane-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4,4-difluoro-6-azaspiro[2.5]octan-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(((1-fluorocyclopropyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(5-fluoroisoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-((cyclopropylmethyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-fluoroquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-fluoroquinoxaline-5-yl)ethyl)amino)benzoic acid; (S)-2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-fluoroquinoxaline-5-yl)ethyl)amino)benzoic acid; (S)-2-((1-(2,7-dicyano-3-(4,4-difluoropiperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2,7-dicyano-3-(4,4-difluoropiperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (S)-2-((1-(7-chloro-2-cyano-3-(4,4-difluoropiperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(7-chloro-2-cyano-3-(4,4-difluoropiperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-6-chloro-3-((1-(2-cyano-7-cyclopropyl-3-(4,4-difluoropiperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(7-chloro-2-cyano-3-(4,4-difluoropiperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(3-(4,4-difluoropiperidine-1-yl)-2,7-dimethylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(3-(4,4-difluoropiperidine-1-yl)-2,7-dimethylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-cyclopropyl-3-(4,4-difluoropiperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methoxyquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-5-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)thiazole-4-carboxylic acid; (R)-2-chloro-5-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)thiazole-4-carboxylic acid; (R)-2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)thiophene-3-carboxylic acid; (R)-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)thiophen-2-carboxylic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-((1S)-1-(trifluoromethyl)-3-azabicyclo[3.1.0]hexane-3-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-cyclopropyl-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-((R)-3-(trifluoromethyl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-((S)-3-(trifluoromethyl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-((1R)-1-(trifluoromethyl)-3-azabicyclo[3.1.0]hexane-3-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyclopropyl-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(3-(4,4-difluoropiperidine-1-yl)-7-methyl-2-(trifluoromethyl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(3-(4,4-difluoropiperidine-1-yl)-7-methyl-2-(trifluoromethyl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-ethylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-6-chloro-3-((1-(2-chloro-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(2-chloro-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-3-((1-(3-(4,4-difluoropiperidine-1-yl)-2,7-dimethylquinoxaline-5-yl)ethyl)amino)-6-methylpicolinic acid; (R)-2-((1-(2-cyano-3-(3,3-dimethylazetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3,3-dimethylazetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(2-cyano-7-methyl-3-morpholinoxaline-5-yl)ethyl)aminobenzoic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-morpholinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(2-cyano-7-methyl-3-(2-oxa-6-azaspiro[3,3]heptan-6-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(2-oxa-6-azaspiro[3,3]heptan-6-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(2-cyano-3-(4,4-dimethylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4,4-dimethylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(2-cyano-3-(3-methoxy-3-methylazetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3-methoxy-3-methylazetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-methyl-4-(trifluoromethyl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-methyl-4-(trifluoromethyl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(2-cyano-3-cyclopropyl-7-methylquinoxaline-5-yl)ethyl)aminobenzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(pyrrolidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(pyrroridine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3,3-difluoropyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(2-cyano-3-(3,3-difluoropyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(3-methoxypyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(3-methoxypyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(((2,2-difluoro-1-methylcyclopropyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-(((1R)-1-(2-cyano-3-(((2,2-difluoro-1-methylcyclopropyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((R)-1-(2-cyano-3-((((S)-2,2-difluoro-1-methylcyclopropyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((R)-1-(2-cyano-3-((((R)-2,2-difluoro-1-methylcyclopropyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-((3,3-difluorocyclobutyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-6-chloro-3-((1-(2-cyano-3-((3,3-difluorocyclobutyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(4,4-difluoro-3-methylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-(((1R)-1-(2-cyano-3-(4,4-difluoro-3-methylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(3,3-difluoro-4-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-(((1R)-1-(2-cyano-3-(3,3-difluoro-4-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(1,1,2,2-tetrafluoro-6-azaspiro[2.5]octan-6-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3,4-dihydroisoquinoline-2(1H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(2-cyano-3-(3,4-dihydroisoquinoline-2(1H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-6-chloro-3-((1-(2-cyano-3-(6-cyano-3,4-dihydroisoquinoline-2(1H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(2-cyano-3-(6-cyano-3,4-dihydroisoquinoline-2(1H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-6-chloro-3-((1-(2-cyano-3-(6-fluoro-3,4-dihydroisoquinoline-2(1H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(2-cyano-3-(6-fluoro-3,4-dihydroisoquinoline-2(1H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(3,4-dihydro-2,7-naphthyridine-2(1H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(2-cyclopropylacetyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(2-cyano-3-(4-(2-cyclopropylacetyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(4-(2-(2,2-difluorocyclopropyl)acetyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-(4-(2-((S)-2,2-difluorocyclopropyl)acetyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-(4-(2-((R)-2,2-difluorocyclopropyl)acetyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-(((1R)-1-(2-cyano-3-(4-(2-(2,2-difluorocyclopropyl)acetyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(1-hydroxy-6-azaspiro[3.5]nonanane-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-(((1R)-1-(2-cyano-3-(1-hydroxy-6-azaspiro[3.5]nonanane-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-((1R)-1-hydroxy-6-azaspiro[3.5]nonanane-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-((1S)-1-hydroxy-6-azaspiro[3.5]nonanane-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(3-(1-methyl-1H-pyrazole-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(3-(1-methyl-1H-pyrazole-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(3-(1-methyl-1H-pyrazole-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(3-(1-methyl-1H-pyrazole-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-((1R,5S)-3-(1-methyl-1H-pyrazole-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-((1R,5S)-3-(1-methyl-1H-pyrazole-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(3-(1-methyl-1H-pyrazole-3-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-((1R,5S)-3-(1-methyl-1H-pyrazole-3-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-((1R,5S)-3-(1-methyl-1H-pyrazole-3-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(3-(1-methyl-1H-pyrazole-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-((1R,5S)-3-(1-methyl-1H-pyrazole-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-((1R,5S)-3-(1-methyl-1H-pyrazole-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(3-(1-methyl-1H-pyrazole-3-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(3-(1-methyl-1H-pyrazole-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(3-(2-oxopiperidine-1-yl)-8-azabicyclo[3.2.1]octan-8-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(2-cyano-7-methyl-3-(2-oxo-[1,4'-bipiperidine]-1'-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(ethoxymethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(2-cyano-3-(4-(ethoxymethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid or a pharmaceutically acceptable salt thereof The compound according to claim 1.

66. (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(methylsulfonyl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(1-oxidethiomorpholino)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-((2-methoxyethyl)(methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-(((1R)-1-(2-cyano-3-(4,4-difluoro-2-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((R)-4,4-difluoro-2-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-4,4-difluoro-2-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-3-(hydroxymethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-Cyano-3-((R)-3-(Hydroxymethyl)piperidine-1-yl)-7-Methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)pyrazine-2-carboxylic acid; (R)-6-chloro-3-((1-(2-cyano-3-((3-(dimethylamino)-3-oxopropyl)(methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(5-methylthiazole-2-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(7,7-difluoro-5-azaspiro[2,4]heptan-5-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(1H-imidazole-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(ethoxymethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 3-(((1R)-1-(3-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; (R)-4-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)thiophene-3-carboxylic acid; 6-Chloro-3-(((R)-1-(2-Cyano-3-((3S,4R)-3,4-Difluoropyrrolidine-1-yl)-7-Methylquinoxaline-5-yl)Ethyl)amino)Picolinic Acid; (R)-6-chloro-3-((1-(2-cyano-3-(3,3-difluoro-4,4-dimethylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-((3,3,3-trifluoropropyl)amino)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-((3-(dimethylamino)-3-oxopropyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(1-methyl-1H-pyrazole-5-yl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(2-cyano-3-(3,3-difluoroazetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3,3-difluoroazetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(2-cyano-7-methyl-3-(1,1,2,2-tetrafluoro-6-azaspiro[2.5]octan-6-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(1-oxa-6-azaspiro[3,3]heptan-6-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(3-(trifluoromethyl)azetidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-((2-methoxyethyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(6-(trifluoromethyl)pyridine-3-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-2-((1-(2-cyano-7-methyl-3-(1-oxa-6-azaspiro[3,3]heptan-6-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-((oxetan-3-ylmethyl)amino)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(3-(4-(1H-pyrazole-1-yl)piperidine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(N-methylacetamide)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(4-methyl-1H-pyrazole-1-yl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(4-(trifluoromethyl)-1H-pyrazole-1-yl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-cis-tetrahydro-1H-flu[3,4-c]pyrrole-5(3H)-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-oxa-7-azaspiro[2.5]octan-7-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-((R)-3-(methylsulfonyl)pyrrolidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-Cyano-3-((3S,5R)-3,5-Difluoropiperidine-1-yl)-7-Methylquinoxaline-5-yl)Ethyl)amino)Picolinic Acid; (R)-6-chloro-3-((1-(2-cyano-3-(2,2-dimethylmorpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(2-oxa-6-azaspiro[3,3]heptan-6-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(7-chloro-2-cyano-3-(3,3-difluoropyrrolidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-Cyano-3-((R)-3,3-Difluoro-5-(Hydroxymethyl)piperidine-1-yl)-7-Methylquinoxaline-5-yl)Ethyl)amino)Picolinic Acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-3,3-difluoro-5-(hydroxymethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-Cyano-3-((R)-3-(dimethylcarbamoyl)pyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-3-(dimethylcarbamoyl)pyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-((1R,5S,6R)-6-(trifluoromethyl)-3-azabicyclo[3.1.0]hexane-3-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-ethylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-((1R,5S,6S)-6-(trifluoromethyl)-3-azabicyclo[3.1.0]hexane-3-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(methyl(3,3,3-trifluoropropyl)amino)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-3-cyanopyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-Cyano-3-((R)-3-Cyanopyrrolidine-1-yl)-7-Methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(7-chloro-2-cyano-3-morpholinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-3-(hydroxymethyl)pyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-Cyano-3-((R)-3-(Hydroxymethyl)pyrrolidine-1-yl)-7-Methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(3-(4-acetylpiperazine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-oxopiperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3,4-dihydro-2,7-naphthyridine-2(1H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((1R,5S,6S)-6-(hydroxymethyl)-3-azabicyclo[3.1.0]hexane-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-Cyano-3-((R)-3-Fluoro-3-(methoxymethyl)pyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-3-fluoro-3-(methoxymethyl)pyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((1R,5S,6R)-6-(methoxymethyl)-3-azabicyclo[3.1.0]hexane-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((1R,5S,6R)-6-(hydroxymethyl)-3-azabicyclo[3.1.0]hexane-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-((R)-2-methylmorpholino)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-3,3-difluoro-2-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((R)-3,3-difluoro-2-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-3,3-difluoro-4-methoxypyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-Cyano-3-((R)-3,3-Difluoro-4-methoxypyrrolidine-1-yl)-7-Methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 3-(((R)-1-(3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; 3-(((R)-1-(3-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-((S)-3-(methylsulfonyl)pyrrolidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-3-fluoropyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((R)-3-fluoropyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((3S,4S)-3,4-difluoropyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(5-(trifluoromethyl)pyridine-2-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-Cyano-3-((R)-3-Fluoro-3-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-3-fluoro-3-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)methyl picolinate; 6-Chloro-3-(((R)-1-(2-cyano-3-((((S)-2,2-difluoro-1-methylcyclopropyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((((R)-2,2-difluoro-1-methylcyclopropyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(3-(N-methylacetamide)azetidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(tetrahydrofuran-3-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-((S)-tetrahydrofuran-3-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-((R)-tetrahydrofuran-3-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3,3-difluoropyrrolidine-1-yl)-7-ethylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-ethyl-3-morpholinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-ethyl-3-(2-oxa-6-azaspiro[3,3]heptan-6-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-2-ethylmorpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((R)-2-ethylmorpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-((S)-2-(trifluoromethyl)morpholino)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-((R)-2-(trifluoromethyl)morpholino)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-2-(difluoromethyl)morpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((R)-2-(difluoromethyl)morpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-((S)-3-methylmorpholino)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-((R)-3-methylmorpholino)quinoxaline-5-yl)ethyl)amino)picolinic acid; 3-(((1R)-1-(3-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-(4-((R)-1-hydroxyethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-(4-((S)-1-hydroxyethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-(4-((R)-1-methoxyethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-(4-((S)-1-methoxyethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-3-methoxypiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((R)-3-methoxypiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 2-(((R)-1-(2-cyano-3-(4-(2-((R)-2,2-difluorocyclopropyl)acetyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(oxetan-3-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(1-methyl-1H-imidazole-4-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(3-methylisoxazole-5-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(5-methylisoxazole-3-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(2-oxo-[1,4'-bipiperidine]-1'-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(2-cyano-7-methyl-3-morpholinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(2-cyano-3-(3,3-difluoropyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-(trifluoromethoxy)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-chloro-2-cyano-6-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-cyano-6-((1-(2-cyano-3-(4,4-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 3-(((1R)-1-(2-cyano-3-(5,5-difluoro-2-azabicyclo[2.2.1]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(2-cyano-7-methyl-3-(2-oxa-6-azaspiro[3,3]heptan-6-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-Cyano-3-((R)-3,3-Difluoro-4-(Hydroxymethyl)pyrrolidine-1-yl)-7-Methylquinoxaline-5-yl)Ethyl)amino)Picolinic Acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-3,3-difluoro-4-(hydroxymethyl)pyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-3,3-difluoro-4-(methoxymethyl)pyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-Cyano-3-((R)-3,3-Difluoro-4-(Methoxymethyl)pyrrolidine-1-yl)-7-Methylquinoxaline-5-yl)Ethyl)amino)Picolinic Acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((1S,4R)-2,2-difluoro-7-azabicyclo[2.2.1]heptan-7-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((1R,4S)-2,2-difluoro-7-azabicyclo[2.2.1]heptan-7-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((1R,5S,6S)-6-(methoxymethyl)-3-azabicyclo[3.1.0]hexane-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(6-methoxy-3-azabicyclo[3.1.0]hexane-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(6-fluoro-3-azabicyclo[3.1.0]hexane-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3,4-dihydro-2,6-naphthyridine-2(1H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(7-cyano-3,4-dihydroisoquinoline-2(1H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(2-oxa-6-azaspiro[3,3]heptan-6-yl)-7-(trifluoromethyl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3,3-difluoropyrrolidine-1-yl)-7-(trifluoromethyl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-Cyano-3-((3R,5R)-3,5-Difluoropiperidine-1-yl)-7-Methylquinoxaline-5-yl)Ethyl)amino)Picolinic Acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(6-methyl-5-oxo-3,4,5,6-tetrahydro-2,6-naphthyridine-2(1H)-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(7-methyl-8-oxo-3,4,7,8-tetrahydro-2,7-naphthyridine-2(1H)-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(1-methyl-6-oxo-1,6-dihydropyridine-3-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(1-methyl-6-oxopiperidine-3-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(3-oxopyrrolidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(3-methyl-4-oxopyrrolidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3,3-dimethyl-4-oxopyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(2,2-dioxidetetrahydro-1H-thieno[3,4-c]pyrrole-5(3H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-((3aS,6aS)-tetrahydro-1H-fluoro[3,4-c]pyrrole-5(3H)-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-((3aR,6aR)-tetrahydro-1H-fluoro[3,4-c]pyrrole-5(3H)-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-morpholino-7-(trifluoromethyl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-(difluoromethyl)-3-morpholinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-ethoxy-3-morpholinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(tetrahydro-2H-pyran-4-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-Cyano-3-((R)-4,4-Difluoro-3-(Hydroxymethyl)piperidine-1-yl)-7-Methylquinoxaline-5-yl)Ethyl)amino)Picolinic Acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-4,4-difluoro-3-(hydroxymethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-2-(hydroxymethyl)morpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((R)-2-(hydroxymethyl)morpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-2-(methoxymethyl)morpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((R)-2-(methoxymethyl)morpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((2R,5R)-2,5-dimethylmorpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((2S,5S)-2,5-dimethylmorpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((2S,5R)-2,5-dimethylmorpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((2R,5S)-2,5-dimethylmorpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 3-(((R)-1-(3-((1R,6S)-2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; 3-(((R)-1-(3-((1S,6R)-2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(2-oxa-6-azaspiro[3,4]octan-6-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 3-(((R)-1-(3-((1R,6S)-3-oxabicyclo[4.1.0]heptan-6-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; 3-(((R)-1-(3-((1S,6R)-3-oxabicyclo[4.1.0]heptan-6-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(1,4-oxazepan-4-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 3-(((R)-1-(3-((1R,5S)-6-oxa-3-azabicyclo[3.2.1]octan-3-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; 3-(((R)-1-(3-((1S,5R)-6-oxa-3-azabicyclo[3.2.1]octan-3-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; 6-Chloro-3-(((1R)-1-(2-Cyano-3-((1S)-1-Fluoro-3-azabicyclo[3.2.0]heptan-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-Cyano-3-((1S)-1-Fluoro-3-azabicyclo[3.2.0]heptan-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((3S,4S)-3-fluoro-4-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((2R,4S)-4-fluoro-2-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((2S,4R)-4-fluoro-2-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((2R,4R)-4-fluoro-2-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((2S,4S)-4-fluoro-2-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-((1S)-1-fluoro-3-azabicyclo[3.1.0]hexane-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-Cyano-3-((1R)-1-Fluoro-3-azabicyclo[3.1.0]hexane-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((R)-3,3-difluorocyclopentyl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-3,3-difluorocyclopentyl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(2-oxa-7-azaspiro[3.5]nonan-7-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(1-oxa-7-azaspiro[3.5]nonan-7-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(6-oxa-2-azaspiro[3,4]octan-2-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-5-(1-((6-chloro-2-(hydroxymethoxy)pyridine-3-yl)amino)ethyl)-7-methyl-3-(5-oxa-2-azaspiro[3,4]octan-2-yl)quinoxaline-2-carbonitrile 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-((S)-1-oxa-7-azaspiro[4,4]nonan-7-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-((R)-1-oxa-7-azaspiro[4,4]nonan-7-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-((S)-2-oxa-7-azaspiro[4,4]nonan-7-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-((R)-2-oxa-7-azaspiro[4,4]nonan-7-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(6,6-difluoro-2-azaspiro[3,3]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(5,5-difluoro-2-azaspiro[3,3]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-5-fluoro-2-azaspiro[3,3]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((R)-5-fluoro-2-azaspiro[3,3]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(6-fluoro-2-azaspiro[3,3]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(6-hydroxy-2-azaspiro[3,3]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-(()-2-methylmorpholino)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-3-((S)-1-hydroxyethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((S)-3-((R)-1-hydroxyethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-3-((R)-3-((S)-1-hydroxyethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-Cyano-3-((R)-3-((R)-1-hydroxyethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4,4-difluoroazepan-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((R)-1-(2-cyano-7-methyl-3-cis-tetrahydro-1H-thieno[3,4-c]pyrrole-5(3H)-ylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2,7-dimethyl-3-morpholinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(7-methyl-3-morpholinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(7-methyl-3-morpholino-2-(trifluoromethyl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-5-(1-((2-(1H-tetrazole-5-yl)phenyl)amino)ethyl)-7-methyl-3-morpholinoquinoxaline-2-carbonitrile; (R)-5-(1-((2-cyanophenyl)amino)ethyl)-7-methyl-3-morpholinoquinoxaline-2-carbonitrile; (R)-5-(1-((6-chloro-2-(1H-tetrazole-5-yl)pyridine-3-yl)amino)ethyl)-7-methyl-3-morpholinoxaline-2-carbonitrile; (R)-5-(1-((6-chloro-2-cyanopyridine-3-yl)amino)ethyl)-7-methyl-3-morpholinoquinoxaline-2-carbonitrile; (R)-2-((1-(2-cyano-7-methyl-3-morpholinoxaline-5-yl)ethyl)amino)-N-methylbenzamide; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-morpholinoxaline-5-yl)ethyl)amino)-N-methylpicolinamide; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(morpholino-d8)quinoxaline-5-yl)ethyl)amino)picolinic acid; (2S,3S,4S,5R)-6-((6-chloro-3-(((R)-1-(2-cyano-7-methyl-3-morpholinoxaline-5-yl)ethyl)amino)picolinoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid or a pharmaceutically acceptable salt thereof The compound according to claim 1.

67. (R)-2-((1-(3-(4-(Bicyclo[1.1.1]pentan-1-yl-3-d)piperidine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-((3-cyanophenyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(((tetrahydrofuran-3-yl)methyl)amino)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-((oxetan-3-ylmethyl)amino)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-((2-cyanoallyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(cyclobutylamino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-((3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(5,6-dihydroimidazo[1,2-a]pyrazine-7(8H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(2,3-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazine-7(8H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(5,6-dihydroimidazo[1,5-a]pyrazine-7(8H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(6,7-dihydropyrazolo[1,5-a]pyrazine-5(4H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-methylpiperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(azepan-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(2-oxa-8-azaspiro[4.5]decane-8-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(2-oxa-7-azaspiro[3.5]nonan-7-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(6-azaspiro[2.5]octan-6-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(azetidine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(2-hydroxy-8-azaspiro[4.5]decane-8-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-methylpiperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(octahydro-2H-4,7-ethanoisoindole-2-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(6,6-dimethyl-3-azabicyclo[3.2.0]heptan-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(2-azaspiro[3,3]heptan-2-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(2-azadispiro[3.1.36.14]decane-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-oxa-7-azaspiro[2.5]octan-7-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(5-methylhexahydropyrrolo[3,4-c]pyrrole-2(1H)-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(2-cyclopropylmorpholino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(2-cyclopropyl-6-methylmorpholino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(3-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(3-azabicyclo[3.1.1]heptan-3-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(3-(3-azabicyclo[3.1.0]hexane-3-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(6-(4-cyanophenyl)-2,6-diazaspiro[3,3]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(2-methylmorpholino)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(2-cyclopropyl-2-methylmorpholino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(3-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(7-azabicyclo[2.2.1]heptan-7-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(2-azaadamantan-2-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(1-(methoxymethyl)-4-methyl-2-azabicyclo[2.1.1]hexane-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(8-((dimethylamino)methyl)-6-oxa-9-azaspiro[4.5]decane-9-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(2-azabicyclo[2.2.2]octan-2-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(3-(2-azabicyclo[2.2.1]heptan-2-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(hexahydro-3,5-methanocyclopenta[b]pyrrole-1(2H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(1-(hydroxymethyl)-6-azabicyclo[3.2.1]octan-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(2-azabicyclo[2.1.1]hexane-2-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(3-methylmorpholino)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(2-methyl-4-(pyridine-3-ylmethyl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(2-methylazetidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(2,3-dimethylmorpholino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(3-hydroxy-2-(2-methoxyphenyl)pyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(3,4-dihydroquinoline-1(2H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(3-hydroxypiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(3-hydroxy-3-methylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(2-(4-hydroxy-4-methyltetrahydro-2H-pyran-3-yl)pyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(8-hydroxy-3-azabicyclo[3.2.1]octan-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(5-hydroxy-2-azabicyclo[2.2.2]octan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(6-hydroxyhexahydro-3,5-methanocyclopenta[b]pyrrole-1(2H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(6-(4-cyanophenyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(6-hydroxy-6-methyl-3-azabicyclo[3.1.1]heptan-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(5-(4-cyanophenyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(5-phenyl-2-azabicyclo[2.2.1]heptan-2-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(3-(7-(tert-butyl)-6,7-dihydropyrazolo[1,5-a]pyrimidine-4(5H)-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(1-methyl-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridine-6-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(5,6,8,9-tetrahydro-7H-imidazo[1,2-d][1,4]diazepine-7-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(pyridine-2-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(pyridine-3-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(3-cyano-1-methyl-1H-pyrazole-4-yl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(1-methyl-1H-pyrazole-4-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(pyridine-4-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-phenylpiperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(4-(4-(aminomethyl)phenyl)piperazine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(3-methylisoxazole-5-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(3-cyanophenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(2,6-dimethylphenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(o-tolyl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(3-cyano-2-methylphenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(2-cyanopyridine-3-yl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(5-cyanopyrimidine-2-yl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(3-cyano-1-methyl-1H-indazole-7-yl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(2-cyanophenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(4-(methylcarbamoyl)phenyl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(4-(4-carbamoylphenyl)piperazine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(4-cyanophenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(4-cyano-2-methylphenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(8-cyanoisoquinoline-5-yl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(4-cyano-7-hydroxynaphthalene-1-yl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(4-cyano-6-hydroxynaphthalene-1-yl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(4,6-dicyanonaphthalene-1-yl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(oxetan-3-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(tetrahydro-2H-pyran-4-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-cyclopropylpiperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(1-methyl-1H-pyrazole-4-carbonyl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(4-benzoylpiperazine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(cyclopentanecarbonyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(cyclopropanecarbonyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(4-acetylpiperazine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(4-(1H-pyrazole-1-yl)piperidine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(4-methyl-1H-pyrazole-1-yl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(1-methyl-1H-pyrazole-3-yl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(4-(1H-pyrazole-3-yl)piperidine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(1-methyl-1H-pyrazole-5-yl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(4-methoxyphenyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-methoxypiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-hydroxypiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-([1,4'-bipiperidine]-1'-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(dimethylamino)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-cyclopentylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-cyclobutylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-cyanopiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(1-oxa-8-azaspiro[4.5]decane-8-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(1-oxa-7-azaspiro[3.5]nonan-7-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-methoxy-4-methylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-cyano-4-methylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(3-(pyridine-2-yl)pyrrolidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(3-(pyridine-4-yl)pyrrolidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(3-phenylpyrrolidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(3-(1,3-dihydroxypropane-2-yl)pyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(1-oxa-6-azaspiro[3,4]octan-6-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(2-oxa-7-azaspiro[4,4]nonan-7-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(spiro[bicyclo[2.2.1]heptan-2,3'-pyrrolidine]-1'-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(8,9-dihydroxy-6-oxa-2-azaspiro[4.5]decane-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(4-(4-cyanophenyl)-3-methylpiperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(2-methyl-4-phenylpiperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(4-(3-cyanophenyl)-2-methylpiperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(4-(2-cyanophenyl)-2-methylpiperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(4-(4-cyanophenyl)-2-methylpiperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(4-(2-cyano-5-methylphenyl)-2-methylpiperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(6-hydroxy-2-azabicyclo[2.2.2]octan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(1,2,3,4-tetrahydro-1,4-epiminonaphthalene-9-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(5,7-dihydro-6H-pyrrolo[3,4-b]pyrazine-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-cyanoisoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(5-(hydroxymethyl)isoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(5-methylisoindoline-2-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(5,6-dimethoxyisoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(tetrahydro-1H,3H-spiro[pyrrolo[2,1-c][1,4]oxazin-4,5'-[1,3]oxadinane]-3'-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(decahydro-2H-cycloocta[c]pyrrole-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(8-azatricyclo[4.3.0.02,5]nonane-8-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(1H,3H,4H-3a,6a-(methanooxymethano)fl[3,4-c]pyrrole-5(6H)-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(8-hydroxy-6-azaspiro[3,4]octan-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(3-(pyridine-2-yl)azetidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(3-(pyridine-3-yl)azetidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(3-phenylazetidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(3-methoxyazetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(3-cyanoazetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(7-(4-cyanophenyl)-2,7-diazaspiro[3.5]nonanane-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(8-hydroxyoctahydro-2H-4,7-methanoisoindole-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(5-methyl-2-azabicyclo[2.2.1]heptan-2-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(1'-methyltetrahydrospiro[fl[3,4-b]pyrrole-3,4'-piperidine]-1(2H)-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(1-(hydroxymethyl)isoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(3-hydroxyoctahydro-1H-indole-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(1-methyloctahydro-2H-isoindole-2-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(methyl((5,6,8,9-tetrahydro-[1,2,4]triazolo[4,3-d][1,4]oxazepine-3-yl)methyl)amino)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(methyl((5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-7-yl)methyl)amino)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-((cyclopropylmethyl)(methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(((1-hydroxy-2,3-dihydro-1H-inden-1-yl)methyl)(methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(dimethylamino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(methyl(1-methyl-2,3-dihydro-1H-inden-2-yl)amino)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-((2-methoxy-2,3-dihydro-1H-inden-1-yl)(methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(3-(4-cyanophenyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(3-(4-cyanophenyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(tetrahydro-2H-pyran-4-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(piperidine-4-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(1-methylpiperidine-4-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(3,6-dihydro-2H-pyran-4-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(1,2,3,6-tetrahydropyridine-4-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(1-methyl-1,2,3,6-tetrahydropyridine-4-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3,7-dimethylquinoxaline-5-yl)ethyl)aminobenzoic acid; (R)-2-((1-(2-cyano-3-(1-(4-cyanophenyl)piperidine-4-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(1-acetylpiperidine-4-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(1-acetyl-1,2,3,6-tetrahydropyridine-4-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-((4-cyanophenyl)ethynyl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(1-methyl-1H-pyrazole-3-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(pyridine-2-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(pyridine-3-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(1-methyl-1H-pyrazole-4-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(1-methyl-1H-imidazole-4-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(1-(4-cyanophenyl)-1H-pyrazole-4-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(pyridine-4-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-phenylquinoxaline-5-yl)ethyl)aminobenzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(p-tolyl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(3-methoxyphenyl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(3-(2-cyanopropan-2-yl)phenyl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(3-cyanophenyl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(1H-pyrazole-4-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(1H-imidazole-4-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(o-tolyl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(1-(4-cyanophenyl)-1H-imidazole-4-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(2-methoxyphenyl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(2-cyanophenyl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-methoxyphenyl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-cyanophenyl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(1-methyl-2-oxopiperidine-4-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4,4-difluorocyclohexyl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(1-methyl-6-oxo-1,6-dihydropyridine-3-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-fluorophenyl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(4-chlorophenyl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-((tetrahydrofuran-3-yl)thio)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(((trifluoromethyl)sulfonyl)oxy)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(((1-fluorocyclopropyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(((3,3-difluorocyclobutyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(((2,2-difluorocyclopropyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-((1-cyclopropyl-2,2,2-trifluoroethyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(2-(trifluoromethyl)-5,6-dihydroimidazo[1,2-a]pyrazine-7(8H)-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4H-thieno[3,4-c]pyrrole-5(6H)-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(2,2-difluoroethyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(2,2,2-trifluoroethyl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(2,2-difluoro-7-azaspiro[3,5]nonanane-7-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(2-(fluoromethyl)morpholino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(2-(2-fluoroethyl)morpholino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(5,5-difluorohexahydrocyclopenta[c]pyrrole-2(1H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(2,2-difluoro-6-azaspiro[3,4]octan-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(6,6-difluoro-2-azaspiro[3,3]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(2-(trifluoromethyl)morpholino)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(2-(fluoromethyl)azetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-fluoroisoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(1-oxoisoindorin-2-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(5,6-difluoroisoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-methyl-3-oxopiperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(3-oxopiperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(3,3-difluoro-4-methoxypiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(3,3-difluoro-4-methylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4,4-difluoro-6-azaspiro[2.5]octan-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(3-(trifluoromethyl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(3,3-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(4,4-difluoro-3-methoxypiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(3,4,4-trifluoropiperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(3,3-difluoro-4-methoxypyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(9,9-difluoro-3-oxa-7-azabicyclo[3.3.1]nonan-7-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(9,9-difluoro-3-azabicyclo[3.3.1]nonane-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(9,9-difluoro-1-(hydroxymethyl)-3-azabicyclo[3.3.1]nonane-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(8,8-difluoro-3-azabicyclo[3.2.1]octan-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(5,5-difluoro-2-azabicyclo[2.2.2]octan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(7,7,9,9-tetrafluoro-3-azabicyclo[3.3.1]nonane-3-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(6,6-difluoro-3-azabicyclo[3.1.1]heptan-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(1-(trifluoromethyl)-3-azabicyclo[3.1.0]hexane-3-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(5,5-difluoro-2-azabicyclo[2.2.1]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(4,4-difluoro-3,5-dimethylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(7,7-difluoro-5-azaspiro[2,4]heptan-5-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(6-(trifluoromethyl)-3-azabicyclo[3.1.0]hexane-3-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(6,6-difluoro-3-azabicyclo[3.1.0]hexane-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(6,7-dihydrothiazolo[4,5-c]pyridine-5(4H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(2-methyl-6,7-dihydrothiazolo[4,5-c]pyridine-5(4H)-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(1,1-dioxidethiomorpholino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(thiazole-2-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(5-(trifluoromethyl)pyridine-2-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(5-(trifluoromethyl)benzo[d]thiazole-2-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(4-methylthiazole-2-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(3-(trifluoromethyl)phenyl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(2-fluorophenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(4-(2-chlorophenyl)piperazine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(2,4-difluorophenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(4-cyano-2-fluorophenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(4-(N-methylsulfamoyl)phenyl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4-(4-fluorophenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(methylsulfonyl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(4-(4-chlorobenzoyl)piperazine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(3-(trifluoromethyl)-1H-pyrazole-1-yl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(2-oxo-[1,4'-bipiperidine]-1'-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4,4-difluoro-[1,4'-bipiperidine]-1'-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(4-(trifluoromethyl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(1,1-difluoro-6-azaspiro[2.5]octan-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(7-methyl-6-oxo-2,7-diazaspiro[4,4]nonanane-2-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(2-oxo-1,7-diazaspiro[4,4]nonan-7-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(7,7-difluoro-2-azaspiro[4,4]nonanane-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(1,1,2,2-tetrafluoro-6-azaspiro[3,4]octan-6-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(4,4-difluoro-3-(hydroxymethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(2-(trifluoromethyl)azetidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(4-(2-cyano-4-(trifluoromethyl)phenyl)-2-methylpiperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(4-(4-fluorophenyl)-2-methylpiperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(4,4-difluoro-2-methylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(3,3-difluoro-2-methylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(3,3,4,4-tetrafluoropyrrolidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(3,5-difluoropiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(4-fluoro-2-(morpholine-4-carbonyl)pyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(6,6-difluoro-2-azabicyclo[2.2.1]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(4,6-dihydro-5H-pyrrolo[3,4-d]thiazole-5-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(2-methyl-4,6-dihydro-5H-pyrrolo[3,4-d]thiazole-5-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(5-fluoroisoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(5-(difluoromethyl)isoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(3-(5-(trifluoromethyl)isoxazole-3-yl)azetidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(3-fluoroazetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(3-(difluoromethyl)azetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-(3-(trifluoromethyl)azetidine-1-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(5,5-difluoro-2-azaspiro[3,3]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(1,1-difluoro-5-azaspiro[2,3]hexane-5-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(3-(7-chloro-3-(hydroxymethyl)-3,4-dihydroisoquinoline-2(1H)-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(3,3-difluoro-2-methylazetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(3-((1-benzyl-2-oxopiperidine-3-yl)(methyl)amino)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(methyl(4,5,6,7-tetrahydrobenzo[d]thiazole-6-yl)amino)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-((3,3-difluorocyclobutyl)(methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-(3-methyl-4-oxo-3,9-diazabicyclo[4.2.1]nonane-9-yl)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(3,3-difluoro-8-azabicyclo[3.2.1]octan-8-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-chloro-2-cyano-7-methylquinoxaline-5-yl)ethyl)aminobenzoic acid; (R)-2-((1-(2-cyano-7-methyl-3-phenoxyquinoxaline-5-yl)ethyl)aminobenzoic acid; (R)-2-((1-(2-cyano-3-(3-cyanophenoxy)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(3-(benzyloxy)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-((tetrahydrofuran-3-yl)oxy)quinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-methoxy-7-methylquinoxaline-5-yl)ethyl)aminobenzoic acid; (R)-2-((1-(2-cyano-3-(4-(ethoxymethyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(diethylamino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-((1-(pyridine-3-yl)ethyl)amino)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-7-methyl-3-((3,3,3-trifluoro-2-methylpropyl)amino)quinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-((1-cyclopropylethyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-2-((1-(2-cyano-3-(isobutylamino)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(3-hydroxy-3-isopropylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; 2-(((1R)-1-(2-cyano-3-(1-isopropyl-7,7-dioxide-7-thia-2-azaspiro[3.5]nonanane-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)benzoic acid; (R)-3-((1-(3-(4-(Bicyclo[1.1.1]pentan-1-yl-3-d)piperidine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-((3-cyanophenyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(((tetrahydrofuran-3-yl)methyl)amino)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(((3,3-difluorocyclobutyl)methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-((2-cyanoallyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(cyclobutylamino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-((3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-((1-cyclopropyl-2,2,2-trifluoroethyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(5,6-dihydroimidazo[1,2-a]pyrazine-7(8H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(2,3-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazine-7(8H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(2-(trifluoromethyl)-5,6-dihydroimidazo[1,2-a]pyrazine-7(8H)-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4H-thieno[3,4-c]pyrrole-5(6H)-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(5,6-dihydroimidazo[1,5-a]pyrazine-7(8H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(6,7-dihydropyrazolo[1,5-a]pyrazine-5(4H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(2,2-difluoroethyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(2,2,2-trifluoroethyl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-methylpiperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(3-(azepan-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(2-oxa-8-azaspiro[4.5]decane-8-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(6-azaspiro[2.5]octan-6-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(3-(azetidine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(2-hydroxy-8-azaspiro[4.5]decane-8-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(2,2-difluoro-7-azaspiro[3.5]nonan-7-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-methylpiperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(octahydro-2H-4,7-ethanoisoindole-2-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-Cyano-3-(6,6-dimethyl-3-azabicyclo[3.2.0]heptan-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(2-azaspiro[3,3]heptan-2-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(2-azadispiro[3.1.36.14]decane-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(5-methylhexahydropyrrolo[3,4-c]pyrrole-2(1H)-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(2-(fluoromethyl)morpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(2-(2-fluoroethyl)morpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(5,5-difluorohexahydrocyclopenta[c]pyrrole-2(1H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(2-cyclopropylmorpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(2-cyclopropyl-6-methylmorpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(3-(3-azabicyclo[3.1.1]heptan-3-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; 3-(((1R)-1-(3-(3-azabicyclo[3.1.0]hexane-3-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(6-(4-cyanophenyl)-2,6-diazaspiro[3,3]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(2,2-difluoro-6-azaspiro[3,4]octan-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(6,6-difluoro-2-azaspiro[3,3]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(2-cyclopropyl-2-methylmorpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 3-(((1R)-1-(3-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; (R)-3-((1-(3-(7-azabicyclo[2.2.1]heptan-7-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; (R)-3-((1-(3-(2-azaadamantan-2-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(1-(methoxymethyl)-4-methyl-2-azabicyclo[2.1.1]hexane-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(8-((dimethylamino)methyl)-6-oxa-9-azaspiro[4.5]decane-9-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(2-(fluoromethyl)azetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(3-(2-azabicyclo[2.2.2]octan-2-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; 3-(((1R)-1-(3-(2-azabicyclo[2.2.1]heptan-2-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(hexahydro-3,5-methanocyclopenta[b]pyrrole-1(2H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(1-(hydroxymethyl)-6-azabicyclo[3.2.1]octan-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(3-(2-azabicyclo[2.1.1]hexane-2-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(2-methyl-4-(pyridine-3-ylmethyl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(2-methylazetidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(2,3-dimethylmorpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(1-oxoisoindorin-2-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-methyl-3-oxopiperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(3-oxopiperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(3,3-difluoro-4-methoxypiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(3-hydroxy-2-(2-methoxyphenyl)pyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(3,3-difluoro-4-methylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3,4-dihydroquinoline-1(2H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(3-hydroxypiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(3-hydroxy-3-methylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(2-(4-hydroxy-4-methyltetrahydro-2H-pyran-3-yl)pyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(4,4-difluoro-3-methoxypiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(3,4,4-trifluoropiperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-Cyano-3-(9,9-Difluoro-3-oxa-7-azabicyclo[3.3.1]nonane-7-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-Cyano-3-(9,9-Difluoro-3-azabicyclo[3.3.1]nonan-3-yl)-7-Methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(9,9-difluoro-1-(hydroxymethyl)-3-azabicyclo[3.3.1]nonan-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-Cyano-3-(8-Hydroxy-3-azabicyclo[3.2.1]octan-3-yl)-7-Methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(8,8-difluoro-3-azabicyclo[3.2.1]octan-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(5-hydroxy-2-azabicyclo[2.2.2]octan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(5,5-difluoro-2-azabicyclo[2.2.2]octan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(7,7,9,9-tetrafluoro-3-azabicyclo[3.3.1]nonane-3-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(6-hydroxyhexahydro-3,5-methanocyclopenta[b]pyrrole-1(2H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(6-(4-cyanophenyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-Cyano-3-(6-Hydroxy-6-methyl-3-azabicyclo[3.1.1]heptan-3-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(5-(4-cyanophenyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(5-phenyl-2-azabicyclo[2.2.1]heptan-2-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(4,4-difluoro-3,5-dimethylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 3-(((1R)-1-(3(7-(tert-butyl)-6,7-dihydropyrazolo[1,5-a]pyrimidine-4(5H)-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(6,7-dihydrothiazolo[4,5-c]pyridine-5(4H)-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(2-methyl-6,7-dihydrothiazolo[4,5-c]pyridine-5(4H)-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(1-methyl-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridine-6-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(5,6,8,9-tetrahydro-7H-imidazo[1,2-d][1,4]diazepine-7-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(1,1-dioxidethiomorpholino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(thiazole-2-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(pyridine-2-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(5-(trifluoromethyl)benzo[d]thiazole-2-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(4-methylthiazole-2-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(pyridine-3-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(3-cyano-1-methyl-1H-pyrazole-4-yl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(1-methyl-1H-pyrazole-4-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(pyridine-4-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-phenylpiperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(3-(4-(4-(aminomethyl)phenyl)piperazine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(3-(trifluoromethyl)phenyl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(3-cyanophenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(2,6-dimethylphenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(o-tolyl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(3-cyano-2-methylphenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(2-cyanopyridine-3-yl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(5-cyanopyrimidine-2-yl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(3-cyano-1-methyl-1H-indazole-7-yl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(2-fluorophenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(3-(4-(2-chlorophenyl)piperazine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(2-cyanophenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(2,4-difluorophenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(4-cyano-2-fluorophenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(4-(N-methylsulfamoyl)phenyl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(4-fluorophenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(4-(methylcarbamoyl)phenyl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(3-(4-(4-carbamoylphenyl)piperazine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(4-cyanophenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(4-cyano-2-methylphenyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(8-cyanoisoquinoline-5-yl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(4-cyano-7-hydroxynaphthalene-1-yl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(4-cyano-6-hydroxynaphthalene-1-yl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(4,6-dicyanonaphthalene-1-yl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(methylsulfonyl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(oxetan-3-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(tetrahydro-2H-pyran-4-yl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-cyclopropylpiperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(1-methyl-1H-pyrazole-4-carbonyl)piperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(3-(4-benzoylpiperazine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; (R)-6-chloro-3-((1-(3-(4-(4-chlorobenzoyl)piperazine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(cyclopentanecarbonyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(cyclopropanecarbonyl)piperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(3-(trifluoromethyl)-1H-pyrazole-1-yl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(1-methyl-1H-pyrazole-3-yl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(3-(4-(1H-pyrazole-3-yl)piperidine-1-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(4-methoxyphenyl)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-methoxypiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-hydroxypiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(3-([1,4'-bipiperidine]-1'-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4,4-difluoro-[1,4'-bipiperidine]-1'-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-(dimethylamino)piperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-cyclopentylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-cyclobutylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(4-(trifluoromethyl)piperidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-cyanopiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(1-oxa-8-azaspiro[4.5]decane-8-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(1,1-difluoro-6-azaspiro[2.5]octan-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-methoxy-4-methylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-cyano-4-methylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(3-(pyridine-2-yl)pyrrolidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(3-(pyridine-4-yl)pyrrolidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(3-phenylpyrrolidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(3-(1,3-dihydroxypropane-2-yl)pyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(1-oxa-6-azaspiro[3,4]octan-6-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(spiro[bicyclo[2.2.1]heptan-2,3'-pyrrolidine]-1'-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(7-methyl-6-oxo-2,7-diazaspiro[4,4]nonan-2-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(8,9-dihydroxy-6-oxa-2-azaspiro[4.5]decane-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(2-oxo-1,7-diazaspiro[4,4]nonan-7-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(7,7-difluoro-2-azaspiro[4,4]nonan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(1,1,2,2-tetrafluoro-6-azaspiro[3,4]octan-6-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(4-(4-cyanophenyl)-3-methylpiperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(2-(trifluoromethyl)azetidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(2-methyl-4-phenylpiperazine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(4-(3-cyanophenyl)-2-methylpiperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(4-(2-cyanophenyl)-2-methylpiperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(4-(2-cyano-4-(trifluoromethyl)phenyl)-2-methylpiperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(4-(4-fluorophenyl)-2-methylpiperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(4-(4-cyanophenyl)-2-methylpiperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(4-(2-cyano-5-methylphenyl)-2-methylpiperazine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(4,4-difluoro-2-methylpiperidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(3,3,4,4-tetrafluoropyrrolidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(6-hydroxy-2-azabicyclo[2.2.2]octan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-Cyano-3-(4-Fluoro-2-(Morpholin-4-Carbonyl)Pyrrolidine-1-yl)-7-Methylquinoxaline-5-yl)Ethyl)Amino)Picolinic Acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(1,2,3,4-tetrahydro-1,4-epiminonaphthalene-9-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4,6-dihydro-5H-pyrrolo[3,4-d]thiazole-5-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(5,7-dihydro-6H-pyrrolo[3,4-b]pyrazine-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(2-methyl-4,6-dihydro-5H-pyrrolo[3,4-d]thiazole-5-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-fluoroisoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-cyanoisoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(isoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(5-(hydroxymethyl)isoindolin-2-yl)-7-methylquinoxalin-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(5-methylisoindoline-2-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(5-(difluoromethyl)isoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(5,6-dimethoxyisoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(5,6-difluoroisoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(tetrahydro-1H,3H-spiro[pyrrolo[2,1-c][1,4]oxazin-4,5'-[1,3]oxadinane]-3'-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(decahydro-2H-cycloocta[c]pyrrole-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(8-azatricyclo[4.3.0.02,5]nonan-8-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(3-(1H,3H,4H-3a,6a-(methanooxymethano)fl[3,4-c]pyrrole-5(6H)-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(8-hydroxy-6-azaspiro[3,4]octan-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(3-(5-(trifluoromethyl)isoxazole-3-yl)azetidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(3-(pyridine-2-yl)azetidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(3-(pyridine-3-yl)azetidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(3-phenylazetidine-1-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3-methoxyazetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3-fluoroazetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3-(difluoromethyl)azetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3-cyanoazetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(7-(4-cyanophenyl)-2,7-diazaspiro[3.5]nonan-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-Cyano-3-(8-Hydroxyoctahydro-2H-4,7-Methanoisoindole-2-yl)-7-Methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(5-methyl-2-azabicyclo[2.2.1]heptan-2-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(1'-methyltetrahydrospiro[fl[3,4-b]pyrrole-3,4'-piperidine]-1(2H)-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(1-(hydroxymethyl)isoindoline-2-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(3-(7-Chloro-3-(hydroxymethyl)-3,4-dihydroisoquinoline-2(1H)-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(3-hydroxyoctahydro-1H-indole-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(1-methyloctahydro-2H-isoindole-2-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(3,3-difluoro-2-methylazetidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(methyl((5,6,8,9-tetrahydro-[1,2,4]triazolo[4,3-d][1,4]oxazepine-3-yl)methyl)amino)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(methyl((5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-7-yl)methyl)amino)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-((cyclopropylmethyl)(methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(((1-hydroxy-2,3-dihydro-1H-inden-1-yl)methyl)(methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(dimethylamino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 3-(((1R)-1-(3-((1-benzyl-2-oxopiperidine-3-yl)(methyl)amino)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(methyl(4,5,6,7-tetrahydrobenzo[d]thiazole-6-yl)amino)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-((3,3-difluorocyclobutyl)(methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(methyl(1-methyl-2,3-dihydro-1H-inden-2-yl)amino)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-((2-methoxy-2,3-dihydro-1H-inden-1-yl)(methyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(3-(4-cyanophenyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(3-methyl-4-oxo-3,9-diazabicyclo[4.2.1]nonane-9-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-Cyano-3-(3,3-Difluoro-8-azabicyclo[3.2.1]octan-8-yl)-7-Methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(3-(4-cyanophenyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(piperidine-4-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(1-methylpiperidine-4-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3,6-dihydro-2H-pyran-4-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(1,2,3,6-tetrahydropyridine-4-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(1-methyl-1,2,3,6-tetrahydropyridine-4-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3,7-dimethylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-(1-methyl-2-oxopiperidine-4-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(1-(4-cyanophenyl)piperidine-4-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(3-(1-acetylpiperidine-4-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4,4-difluorocyclohexyl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(3-(1-acetyl-1,2,3,6-tetrahydropyridine-4-yl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-((4-cyanophenyl)ethynyl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(1-methyl-1H-pyrazole-3-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(pyridine-2-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(pyridine-3-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(1-methyl-1H-pyrazole-4-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(1-methyl-1H-imidazole-4-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(1-(4-cyanophenyl)-1H-pyrazole-4-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(pyridine-4-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-phenylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(p-tolyl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3-methoxyphenyl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3-(2-cyanopropan-2-yl)phenyl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3-cyanophenyl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(1H-pyrazole-4-yl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(1H-imidazole-4-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(o-tolyl)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(1-(4-cyanophenyl)-1H-imidazole-4-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(2-methoxyphenyl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(2-cyanophenyl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-methoxyphenyl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-fluorophenyl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(3-(4-chlorophenyl)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(4-cyanophenyl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(3-chloro-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-((tetrahydrofuran-3-yl)thio)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-phenoxyquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(3-cyanophenoxy)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-7-methyl-3-(((trifluoromethyl)sulfonyl)oxy)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-3-((1-(3-(benzyloxy)-2-cyano-7-methylquinoxaline-5-yl)ethyl)amino)-6-chloropicolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-((tetrahydrofuran-3-yl)oxy)quinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-methoxy-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-hydroxy-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(diethylamino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-((1-(pyridine-3-yl)ethyl)amino)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-7-methyl-3-((3,3,3-trifluoro-2-methylpropyl)amino)quinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-((1-cyclopropylethyl)amino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; (R)-6-chloro-3-((1-(2-cyano-3-(isobutylamino)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-cyano-3-(3-hydroxy-3-isopropylpyrrolidine-1-yl)-7-methylquinoxaline-5-yl)ethyl)amino)picolinic acid; 6-Chloro-3-(((1R)-1-(2-Cyano-3-(1-Isopropyl-7,7-Dioxide-7-Thi-2-Azaspiro[3.5]nonan-2-yl)-7-Methylquinoxaline-5-yl)Ethyl)Amino)Picolinic Acid or a pharmaceutically acceptable salt thereof The compound according to claim 1.

68. A pharmaceutical composition comprising a compound or salt according to any one of claims 1 to 67 together with a pharmaceutically acceptable carrier, excipient, or diluent.

69. A method for treating a disease or disorder related to the regulation of phosphoinositide 3 kinase (PI3K), comprising administering to a patient in need of treatment a therapeutically effective amount of a compound according to any one of claims 1 to 67, or a pharmaceutical composition according to claim 68.

70. The method according to claim 69, wherein PI3K is PI3Kα.

71. The method according to claim 69 or claim 70, wherein the PI3K associated with the disease or disorder has the H1047R mutation.

72. The method according to any one of claims 69 to 71, wherein the disease or disorder is cancer.

73. The method according to claim 69, wherein the cancer is endometrial cancer, gastric cancer, leukemia, lymphoma, sarcoma, colorectal cancer, lung cancer, ovarian cancer, skin cancer, head and neck cancer, breast cancer, brain cancer, or prostate cancer.

74. The method according to any one of claims 69 to 71, wherein the disease or disorder is CLOVES syndrome (congenital lipomatous hypergrowth, vascular malformation, epidermal nevus, scoliosis / skeletal and spinal syndrome) or PIK3Cα-associated hypergrowth syndrome (PROS).

75. A method for inhibiting phosphoinositide 3 kinase (PI3K), comprising administering to a patient in need of inhibition a therapeutically effective amount of a compound according to any one of claims 1 to 67, or a pharmaceutical composition according to claim 68.

76. A method for treating cancer or a disorder, comprising administering to a patient in need of treatment a therapeutically effective amount of a compound according to any one of claims 1 to 67, or a pharmaceutical composition according to claim 68.

77. The method according to claim 72, wherein the cancer is endometrial cancer, gastric cancer, leukemia, lymphoma, sarcoma, colorectal cancer, lung cancer, ovarian cancer, skin cancer, head and neck cancer, breast cancer, brain cancer, or prostate cancer.

78. A method for treating cancer, comprising administering a compound according to any one of claims 1 to 67, or a pharmaceutical composition according to claim 68, and a KRAS inhibitor to a patient in need thereof, wherein the cancer is breast cancer, uterine carcinosarcoma, endometrial cancer, colorectal adenocarcinoma, gastric adenocarcinoma, head and neck squamous cell carcinoma, bile duct cancer, esophageal adenocarcinoma, bladder cancer, lung squamous cell carcinoma, cranial glioma, adrenocortical carcinoma, hepatocellular carcinoma, sarcoma, prostate adenocarcinoma, renal cell carcinoma, lung adenocarcinoma, ovarian cystadenocarcinoma, glioblastoma multiforme, or melanoma.

79. A method for treating cancer, comprising administering a compound according to any one of claims 1 to 67, or a pharmaceutical composition according to claim 68, and a mutant-selective KRAS inhibitor to a patient in need thereof, wherein the cancer is breast cancer, uterine carcinosarcoma, endometrial cancer, colorectal adenocarcinoma, gastric adenocarcinoma, head and neck squamous cell carcinoma, bile duct cancer, esophageal adenocarcinoma, bladder cancer, lung squamous cell carcinoma, cranial glioma, adrenocortical carcinoma, hepatocellular carcinoma, sarcoma, prostate adenocarcinoma, renal cell carcinoma, lung adenocarcinoma, ovarian cystadenocarcinoma, glioblastoma multiforme, or melanoma.

80. A compound according to any one of claims 1 to 67, or a pharmaceutical composition according to claim 68, for use in combination with a KRAS inhibitor in the treatment of cancer, wherein the cancer is breast cancer, uterine carcinosarcoma, endometrial cancer, colorectal adenocarcinoma, gastric adenocarcinoma, head and neck squamous cell carcinoma, bile duct cancer, esophageal adenocarcinoma, bladder cancer, lung squamous cell carcinoma, cranial glioma, adrenocortical carcinoma, hepatocellular carcinoma, sarcoma, prostate adenocarcinoma, renal cell carcinoma, lung adenocarcinoma, ovarian cystadenocarcinoma, glioblastoma multiforme, or melanoma.

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