Allosteric chromenone inhibitors of phosphoinositide 3-kinase (PI3K) for the treatment of cancer

Abstract

The present disclosure relates to compounds of formula (I) or pharma- ceutically acceptable salts thereof as allosteric chromenone inhibitors of phosphoinositide 3-kinase (PI3K) useful for treating diseases or disorders associated with PI3K regulation, according to formula (I): (I), wherein R, R1, R2, R3, R4, R5, R6, R7, and R8 are as defined herein. The present disclosure also relates to methods of making and using compounds of formula (I) or pharma- ceutically acceptable salts thereof. [Formula 1] TIFF2024520417001135.tif33128

Description

Technical Field

[0001] The present invention is directed to allosteric chromenone inhibitors of phosphoinositide 3-kinase (PI3K) useful for the treatment of diseases or disorders associated with PI3K modulation. The present invention relates to compounds and compositions that inhibit PI3K, methods of treating (or uses for treating) diseases or disorders associated with PI3K (e.g., CLOVES syndrome (Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevus, Scoliosis / Skeletal and Spinal Syndrome), PIK3CA-related overgrowth 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 uses or methods of use of PI3K inhibitors in combination with one or more additional cancer therapies.

Background Art

[0002] Cell activities can be regulated by external signals that stimulate or inhibit intracellular events. The process by which a stimulatory or inhibitory signal is transmitted into and within a cell to elicit an intracellular response is referred to as signal transduction. Over the past several decades, cascades of signal transduction events have been elucidated and have been found to play central roles in various biological responses. Defects in various components of signal transduction pathways have been found to be the cause of a vast number of diseases, including numerous forms of cancer, inflammatory disorders, metabolic disorders, vascular, and neurological diseases (Gaestel et al. Current Medicinal Chemistry (2007) 14:2214-2234).

[0003] Kinases represent an important class of signaling molecules. Kinases can generally be classified into protein kinases, lipid kinases, and certain kinases that exhibit dual specificity. Protein kinases are enzymes that phosphorylate other proteins and / or themselves (i.e., autophosphorylation). Protein kinases are generally classified into three major groups based on their substrate utilization: tyrosine kinases that primarily phosphorylate substrates on tyrosine residues (e.g., erb2, PDGF receptor, EGF receptor, VEGF receptor, src, abl), serine / threonine kinases that primarily phosphorylate substrates on serine and / or threonine residues (e.g., mTorC1, mTorC2, ATM, ATR, DNA-PK, Akt), and dual specificity kinases that phosphorylate substrates on tyrosine, serine, and / or threonine residues.

[0004] Lipid kinases are enzymes that catalyze the phosphorylation of intracellular lipids. These enzymes, as well as the resulting phosphorylated lipids and lipid-derived biologically active organic molecules, play roles in many different physiological processes, including cell growth, migration, adhesion, and differentiation. A particular group of lipid kinases includes 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 kinase, and sphingosine kinase.

[0005] 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 disease states, including allergic contact dermatitis, rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, chronic obstructive pulmonary disorder, psoriasis, multiple sclerosis, asthma, disorders associated with diabetic complications, and cardiovascular inflammatory complications such as acute coronary syndrome.

[0006] PI3K is a member of a unique conserved family of intracellular lipid kinases that phosphorylate the 3'-OH group on phosphatidylinositol or phosphoinositides. The PI3K family includes 15 kinases with different substrate specificities, expression patterns, and regulatory modes (Katso et al., Annu Rev Cell Dev Biol. 2001;17:615-75). Class I PI3Ks (p110α, p110β, p110δ, and p110γ) are typically activated by tyrosine kinases or G protein-coupled receptors to generate PIP3, which engages effectors present in the pathways of downstream effectors such as Akt / PDK1, mTOR, Tec family kinases, and Rho family GTPases. Class II and III PI3Ks play important roles in intracellular trafficking by the synthesis of PI(3)P and PI(3,4)P2.

[0007] PI3K isoforms are involved in, for example, various human cancers and disorders. Mutations in the genes encoding PI3K isoforms, or mutations that cause upregulation of PI3K isoforms, are thought to occur in many human cancers. Mutations in the genes encoding PI3K isoforms are point mutations clustered within several hotspots in the helix and kinase domains. Due to the high rate of PI3K mutations, targeting this pathway may provide beneficial therapeutic opportunities.

[0008] Genetic modifications of genes in PI3K signaling are thought to be involved in various cancers such as endometrial cancer, breast cancer, esophageal squamous cell carcinoma, cervical squamous cell carcinoma, cervical adenocarcinoma, colorectal adenocarcinoma, bladder urothelial carcinoma, glioblastoma, ovarian cancer, non-small cell lung cancer, esophagogastric cancer, schwannoma, head and neck squamous cell carcinoma, melanoma, esophagogastric adenocarcinoma, soft tissue sarcoma, prostate cancer, fibrolamellar carcinoma, hepatocellular carcinoma, diffuse glioma, colorectal cancer, pancreatic cancer, cholangiocarcinoma, B-cell lymphoma, mesothelioma, adrenocortical carcinoma, non-clear cell renal cell carcinoma, clear cell renal cell carcinoma, germ cell tumor, thymic tumor, pheochromocytoma, other neuroepithelial tumors, thyroid cancer, leukemia, and encapsulated glioma (Goncalves MD, Hopkins BD, Cantley LC. Phosphatidylinositol 3-Kinase, Growth Disorders, and Cancer. N Engl J Med. 2018 Nov 22;379(21):2052-2062).

[0009] The alpha (α) isoform of PI3K, for example, is involved in various human cancers. It has been shown that angiogenesis selectively requires the α isoform of PI3K under the control of endothelial cell migration. (Graupera et al, Nature 2008;453;662-6). Mutations in the gene encoding PI3Kα, or mutations leading to upregulation of lPI3Kα, are thought to occur in many human cancers such as cancers of the lung, stomach, endometrium, ovary, bladder, breast, colon, brain, prostate, and skin. Mutations in the gene encoding PI3Kα are clustered point mutations within several hotspots in helices 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 provide beneficial therapeutic opportunities. Other PI3K isoforms such as PI3Kδ or PI3Kγ are mainly expressed in hematopoietic cells, but together with PI3Kβ, PI3Kα is constitutively expressed.

[0010] Mutated PI3Kα is involved in brain metastases of HR+ / HER2-metastatic breast cancer. The development of brain-permeable PI3Kα inhibitors may provide a therapeutic effect improved over current PI3Kα inhibitors. (Fitzgerald et al., Association between PIK3CA mutation status and development of brain metastases in HR+ / HER2-metastatic breast cancer. Ann Oncol 30:v110, 2019 (suppl 5)).

[0011] Due to the central role of PI3Kα in the regulation of glucose homeostasis in organisms, PI3K inhibition in patients often causes hyperglycemia and / or hyperinsulinemia (Busaidy NL, et al, Management of metabolic effects associated with anticancer agents targeting the PI3K-Akt-mTOR pathway. J Clin Oncol 2012;30:2919-28). When blood insulin concentration is high, it may exert a mitogenic and / or anti-apoptotic effect on cancer cells, and thus may nullify the anti-proliferative effect of PI3K inhibitors (Blouin M-J, et al, Abstract 4615: The hyperinsulinemia caused by PI3K inhibitors attenuates their antineoplastic efficacy, but can be minimized by co-administration of metformin. Cancer Res 2013;73:4615).

[0012] In the context of cancers having mutant PI3Kα, one way to address the problem of compensatory production of insulin and / or glucose by systemic PI3Kα inhibition is to develop inhibitors with enhanced selectivity for mutant PI3Kα over wild-type PI3Kα. This increases the opportunity for drug administration that selectively inhibits the pathological signaling of mutant PI3Kα in cancer cells without affecting wild-type PI3Kα in host tissues that control whole-body metabolism (Okkenhaug K, Graupera M, Vanhaesebroeck B. Targeting PI3K in Cancer: Impact on Tumor Cells, Their Protective Stroma, Angiogenesis, and Immunotherapy. Cancer Discov. 2016 Oct;6(10):1090-1105), and thus toxicity will be limited, higher doses of administration will be possible, and more complete inhibition of the drug target will be achievable (Ariella B. Hanker, et al, Challenges for the clinical development of PI3K inhibitors: Strategies to improve their impact in solid tumors. Cancer Discov. 2019 Apr;9(4):482-491).

[0013] Currently, PI3Kα inhibitors have approximately equal potency against wild-type and mutant PI3Kα. Mutant-selective inhibitors have been difficult to understand because the position of the PI3Kα mutation is far from the active site. Thus, inhibitors targeting a second peripheral binding pocket near known mutations (e.g., H1047R) may provide a means for selective PI3Kα inhibition. Therefore, targeting the mutant peripheral binding pocket of PI3Kα provides a useful therapeutic target for drug development.

[0014] Thus, kinases, such as lipid kinases like PI3K, are major targets for drug development. The present invention provides a new class of kinase inhibitors. SUMMARY OF THE INVENTION

[0015] In one aspect, the present invention provides a compound of formula (I):

Chemical formula

Chemical formula

[0016] In another aspect, the present invention provides a pharmaceutical composition comprising a compound of formula (I), (II), or (III), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier.

[0017] In another aspect, the present invention provides a method of modulating PI3K (e.g., PI3Kα) activity (e.g., in vitro or in vivo), the method comprising contacting a cell with a therapeutically effective amount of a compound of formula (I), formula (II), or formula (III), or a pharmaceutically acceptable salt thereof.

[0018] In some aspects, the present invention provides a method of treating or preventing a disease or disorder disclosed herein in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I), (II), or (III), or a pharmaceutically acceptable salt thereof.

[0019] In some aspects, the present invention provides a method of treating or preventing a disease or disorder disclosed herein in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I), (II), or (III), or a pharmaceutically acceptable salt thereof.

[0020] In some aspects, the present invention provides a method of treating a disease or disorder disclosed herein in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I), (II), or (III), or a pharmaceutically acceptable salt thereof.

[0021] In some aspects, the present invention provides a method of treating a disease or disorder disclosed herein in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I), (II), or (III), or a pharmaceutically acceptable salt thereof.

[0022] In another aspect, the present invention provides a compound of formula (I), (II), or (III), or a pharmaceutically acceptable salt thereof for use in therapy.

[0023] In another aspect, the present invention provides a compound of formula (I), formula (II), or formula (III), or a pharmaceutically acceptable salt thereof for use in modulating PI3K (e.g., PI3Kα) activity (e.g., in vitro or in vivo).

[0024] In another aspect, the present invention provides a compound of formula (I), (II), or (III), or a pharmaceutically acceptable salt thereof, for use in the selective inhibition of mutant PI3Kα over wild-type PI3Kα.

[0025] In another aspect, the present invention provides a compound of formula (I), (II), or (III), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a disease or disorder disclosed herein.

[0026] In another aspect, the present invention provides a compound of formula (I), (II), or (III), or a pharmaceutically acceptable salt thereof, for use in the treatment of a disease or disorder disclosed herein.

[0027] In another aspect, the present invention provides the use of a compound of formula (I), formula (II), or formula (III), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for regulating PI3K (e.g., PI3Kα) activity (e.g., in vitro or in vivo).

[0028] In another aspect, the present invention provides the use of a compound of formula (I), (II), or (III), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating or preventing a disease or disorder disclosed herein.

[0029] In another aspect, the present invention provides the use of a compound of formula (I), (II), or (III), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating a disease or disorder disclosed herein.

[0030] In another aspect, the present invention provides a method for preparing a compound of formula (I), formula (II), or formula (III), or a pharmaceutically acceptable salt thereof.

[0031] In another aspect, the present invention provides a method for preparing a compound, comprising one or more steps described herein.

[0032] In another aspect, the present invention provides a compound obtainable by a method for preparing a compound described herein (e.g., a method comprising one or more steps described in the schemes), or provides the obtained compound.

[0033] In another aspect, the present invention provides an intermediate described herein that is suitable for use in a method for preparing a compound described herein (e.g., the intermediate is selected from the intermediates described in the examples).

[0034] Other features and advantages of the present invention will become apparent from the following detailed description and claims.

BEST MODE FOR CARRYING OUT THE INVENTION

[0035] The present invention provides a method for treating, preventing or ameliorating a disease or disorder (or use in the treatment, prevention or amelioration of a disease or disorder), which comprises administering a therapeutically effective amount of a PI3K inhibitor of the present invention to a patient in need thereof, wherein PI3K plays a role. The method (or use) of the present invention can be used for the treatment of various PI3K-dependent diseases and disorders.

[0036] 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, or head and neck cancer). In some embodiments, diseases or disorders associated with PI3K include CLOVES syndrome (Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Scoliosis / Skeletal and Spinal Syndrome), PIK3CA-related overgrowth syndrome (PROS), endometrial cancer, breast cancer, esophageal squamous cell carcinoma, cervical squamous cell carcinoma, cervical adenocarcinoma, colorectal adenocarcinoma, bladder urothelial carcinoma, glioblastoma, ovarian cancer, non-small cell lung cancer, esophagogastric cancer, schwannoma, head and neck squamous cell carcinoma, melanoma, esophagogastric adenocarcinoma, soft tissue sarcoma, prostate cancer, fibrolamellar carcinoma, hepatocellular carcinoma, diffuse glioma, colorectal cancer, pancreatic cancer, cholangiocarcinoma, B-cell lymphoma, mesothelioma, adrenocortical carcinoma, non-clear cell renal cell carcinoma, clear cell renal cell carcinoma, germ cell tumor, thymic tumor, pheochromocytoma, other neuroepithelial tumors, thyroid cancer, leukemia, and encapsulated glioma, but are not limited thereto.

[0037] Details of the invention are set forth in the following appended description. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, exemplary methods and materials are described herein. Other features, objects, and advantages of the invention will be apparent from the description and claims. In this specification and the appended claims, the singular forms also include the plural unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents and publications cited herein are incorporated herein by reference in their entirety.

[0038] Definitions The articles “a” and “an” refer to one, or more than one (e.g., at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element.

[0039] The term "and / or" means "and" or "or" whichever is applicable, unless otherwise indicated.

[0040] The terms "administer", "administering", or "administration" refer to either direct administration to a subject of a disclosed compound, or a pharmaceutically acceptable salt of a disclosed compound, or a composition.

[0041] The term "alkenyl" refers to a straight-chain or branched-chain unsaturated hydrocarbon containing 2 to 12 carbon atoms. An "alkenyl" group contains at least one double bond in the chain. The double bond of the alkenyl group may not be conjugated or may be conjugated to another unsaturated group. Examples of alkenyl groups include ethenyl, propenyl, n-butenyl, iso-butenyl, pentenyl, or hexenyl.

[0042] The term "alkoxy" refers to a straight-chain or branched-chain saturated hydrocarbon containing 1 to 12 carbon atoms and containing a terminal "O" in the chain, i.e., -O(alkyl). Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, butoxy, t-butoxy, or pentyloxy groups.

[0043] The term "alkyl" refers to a straight-chain or branched-chain saturated hydrocarbon containing 1 to 12 carbon atoms, preferably 1 to 6 carbon atoms. Examples of (C1-C6) alkyl groups include, but are not limited to, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl, and isohexyl.

[0044] The term "alkynyl" refers to a straight-chain or branched-chain unsaturated hydrocarbon containing 2 to 12 carbon atoms. An "alkynyl" group contains at least one triple bond in the chain. Examples of alkynyl groups include ethynyl, propargyl, n-butynyl, iso-butynyl, pentynyl, or hexynyl.

[0045] The term "aromatic" means a planar ring having 4n + 2 electrons in a conjugated system. As used herein, "conjugated system" means a system of bonding p-orbitals having delocalized electrons, which system may include lone pairs of electrons.

[0046] The term "aryl", unless otherwise defined, refers to a cyclic aromatic hydrocarbon group having 1 to 3 aromatic rings, including monocyclic or bicyclic groups such as phenyl, biphenyl, or naphthyl. When including 2 aromatic rings (such as bicyclic), the aromatic rings of the aryl group may be bonded at one point (e.g., biphenyl) or may be fused (e.g., naphthyl). Further, when containing two fused rings, the aryl group as defined herein may have one or more saturated or partially unsaturated rings fused to a completely unsaturated aromatic ring. Exemplary ring systems of these aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl, anthracenyl, phenalenyl, phenanthrenyl, indanyl, indenyl, tetrahydronaphthalenyl, and tetrahydrobenzoannulenyl.

[0047] The term "carrier" encompasses carriers, excipients, and diluents, and means a material, composition, or vehicle such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material that is involved in the transport or conveyance of a pharmaceutical from one organ or part of the body to another organ or part of the body of a subject.

[0048] The term "cyano" means a substituent having a carbon atom bonded to a nitrogen atom by a triple bond, i.e., C≡N.

[0049] The term "cycloalkyl" means a monocyclic or polycyclic saturated carbon ring containing 3 to 18 carbon atoms, preferably 3 to 10 carbon atoms. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptanyl, cyclooctanyl, norbornyl, norbornenyl, bicyclo[2.2.2]octanyl, and bicyclo[2.2.2]octenyl.

[0050] Unless otherwise indicated, the term "disorder" means the term "disease", "condition", or "ailment" and is used interchangeably therewith.

[0051] The term "haloalkoxy" refers to an alkoxy group as defined herein that is substituted with one or more halogens. Examples of haloalkoxy groups include, but are not limited to, trifluoromethoxy, difluoromethoxy, pentafluoroethoxy, and trichloromethoxy.

[0052] The term "haloalkyl" refers to an alkyl group as defined herein that is substituted with one or more halogens. Examples of haloalkyl groups include, but are not limited to, trifluoromethyl, difluoromethyl, pentafluoroethyl, and trichloromethyl.

[0053] The term "halogen" or "halo" refers to fluorine, chlorine, bromine, or iodine.

[0054] Unless otherwise defined, the term "heteroaryl" means a monocyclic or polycyclic aromatic radical having 5 to 24 ring atoms, preferably 5 to 10 ring atoms, including one or more ring heteroatoms selected from N, O, S, P, or B, preferably 1, 2, 3, or 4 ring heteroatoms selected from N, O, or S, with the remaining ring atoms being C. The polycyclic aromatic radical includes two or more fused rings and may further include two or more spiro-fused rings, such as bicyclic, tricyclic, tetracyclic, etc. Unless otherwise clearly defined, "fused" means two rings sharing two ring atoms. Unless otherwise clearly defined, "spiro-fused" means two rings sharing one ring atom. Heteroaryl as defined herein also means a bicyclic heteroaromatic group in which the heteroatom is selected from N, O, S, P, or B, preferably N, O, or S. Heteroaryl as defined herein also means a tricyclic heteroaromatic group containing one or more ring heteroatoms selected from N, O, S, P, or B, preferably N, O, or S. Heteroaryl as defined herein also means a tetracyclic heteroaromatic group containing one or more ring heteroatoms selected from N, O, S, P, or B, preferably N, O, or S. Examples of heteroaromatic groups include, but are not limited to, furyl, thienyl, pyrrolyl, pyridyl, pyrazolyl, pyrimidinyl, imidazolyl, isoxazolyl, oxazolyl, oxadiazolyl, pyrazinyl, indolyl, thiophen-2-yl, quinolyl, benzopyranyl, isothiazolyl, thiazolyl, thiadiazole, indazole, benzimidazolyl, thieno[3,2-b]thiophene, triazolyl, triazinyl, imidazo[1,2-b]pyrazolyl, furo[2,3-c]pyridinyl, imidazo[1,2-a]pyridinyl, indazolyl, pyrrolo[2,3-c]pyridinyl, pyrrolo[3,2-c]pyridinyl, pyrazolo[3,4-c]pyridinyl, thieno[3,2-c]pyridinyl, thieno[2,3-c]pyridinyl, thieno[2,3-b] pyridinyl, benzothiazolyl, indolinyl, indolinonyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, benzofuranyl, chromanyl, thiochromanyl, tetrahydroquinolinyl, dihydrobenzothiazinyl, quinolinyl, isoquinolinyl, 1,6-naphthyridinyl, benzo[de]isoquinolinyl, pyrido[4,3-b][1,6]naphthyridinyl, thieno[2,3-b]pyrazinyl, quinazolinyl, tetrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, isoindolyl, pyrrolo[2,3-b]pyridinyl, pyrrolo[3,4-b]pyridinyl, pyrrolo[3,2-b]pyridinyl, imidazo[5,4-b]pyridinyl, pyrrolo[1,2-a]pyrimidinyl, tetrahydropyrrolo[1,2-a]pyrimidinyl, 3,4-dihydro-2H-1-pyrrolo[2,1-b]pyrimidine, dibenzo[b,d]thiophene, pyridin-2-one, furo[3,2-c]pyridinyl, furo[2,3-c]pyridinyl, 1H-pyrido[3,4-b][1,4]thiazinyl, benzoxazolyl, benzoisoxazolyl, furo[2,3-b]pyridinyl, benzothiophenyl, 1,5-naphthyridinyl, furo[3,2-b]pyridine, [1,2,4]triazolo[1,5-a]pyridinyl, benzo[1,2,3]triazolyl, imidazo[1,2-a]pyrimidinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, benzo[c][1,2,5]thiadiazolyl, benzo[c][1,2,5]oxadiazole, 1,3-dihydro-2H-benzo[d]imidazol-2-one, 3,4-dihydro-2H-pyrazolo[1,5-b][1,2]oxazinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridinyl, thiazolo[5,4-d]thiazolyl, imidazo[2,1-b][1,3,4]thiadiazolyl, thieno[2,3-b] It includes pyrrolyl and 3H-indolyl. Further, when containing two or more fused rings, the heteroaryl group defined herein may have one or more saturated or partially unsaturated rings fused to one or more completely unsaturated aromatic rings. In a heteroaryl ring system containing three or more fused rings, the saturated or partially unsaturated ring can be further fused to the saturated or partially unsaturated rings described herein. Further, when containing three or more fused rings, the heteroaryl group defined herein may have one or more saturated or partially unsaturated spiro-fused rings. Any saturated or partially unsaturated ring described herein is optionally substituted with one or more oxo groups. Exemplary ring systems of these heteroaryl groups include, for example, indolinyl, indolinonyl, dihydrobenzothiophenyl, dihydrobenzofuran, chromanyl, thiochromanyl, tetrahydroquinolinyl, dihydrobenzothiazine, 3,4-dihydro-1H-isoquinolinyl, 2,3-dihydrobenzofuranyl, benzofuranonyl, oxyindolyl, indolyl, 1,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-onyl, 7,8-dihydro-6H-pyrido[3,2-b]pyrrolidinyl, 8H-pyrido[3,2-b]pyrrolidinyl, 1,5,6,7-tetrahydrocyclopenta[b]pyrazolo[4,3-e]pyridinyl, 7,8-dihydro-6H-pyrido[3,2-b]pyrrolidinyl, pyrazolo[1,5-a]pyrimidin-7(4H)-onyl, 3,4-dihydropyrazino[1,2-a]indol-1(2H)-onyl, benzo[c][1,2]oxaborol-1(3H)-olyl, 6,6a,7,8-tetrahydro-9H-pyrido[2,3-b]pyrrolo[1,2-d][1,4]oxazin-9-onyl, and 6a’,7’-dihydro-6’H,9’H-spiro[cyclopropane-1,8’-pyrido[2,3-b]pyrrolo[1,2-d][1,4] It contains oxazin]-9'-onyl. Further exemplary bicyclic heteroaryl groups include, but are not limited to, indole, benzothiophene, benzofuran, isoindole, benzo[c]thiophene, isobenzofuran, indazole, benzimidazole, benzoxazole, benzothiazole, benzisoxazole, benzisothiazole, pyrrolopyridine, furopyridine, thienopyridine, pyrazolopyridine, isoxazolopyridine, isothiazolopyridine, imidazopyridine, oxazolopyridine, thiazolopyridine, pyrrolopyridazine, pyrrolopyrimidine, pyrrolopyrazine, furopyridazine, furopyrimidine, furopyrazine, thienopyridazine, thienopyrimidine, thienopyrazine, pyrazolopyrimidine, pyrazolopyridazine, pyrazolopyrazine, isoxazolopyridazine, isoxazolopyrimidine, isoxazolopyrazine, isothiazolopyridazine, isothiazolopyrimidine, isothiazolopyrazine, imidazopyridazine, imidazopyrimidine, imidazopyrazine, oxazolopyridazine, oxazolopyrimidine, oxazolopyrazine, thiazolopyridazine, thiazolopyrimidine, thiazolopyrazine, quinazoline, quinoxaline, cinnoline, phthalazine, pyridopyridazine, pyridopyrimidine, pyridopyrazine, pyridazinopyridazine, pyrimidopyridazine, pyrazinopyridazine, pyrimidopyrimidine, pteridine, pyrazinopyrazine, pyridotriazine, pyridazinotriazine, pyrimidotriazine, and pyrazinotriazine.

[0055] The terms "heterocyclyl", "heterocyclic", or "heterocycloalkyl" mean a monocyclic or polycyclic ring containing 3 to 24 atoms, preferably 3 to 10 atoms, including carbon and one or more heteroatoms selected from N, O, S, P, or B, preferably 1, 2, 3, or 4 heteroatoms selected from N, O, and S, and the ring is not aromatic. Examples of heterocyclyl rings include, but are not limited to, oxetanyl, azetidinyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, oxazolinyl, oxazolidinyl, thiazolinyl, thiazolidinyl, pyranyl, thiopyranyl, tetrahydropyranyl, dioxalinyl, piperidinyl, morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S-dioxide, piperazinyl, azepinyl, oxepinyl, diazepinyl, tropanyl, oxazolidinonyl, and homotropanyl.

[0056] The term "hydroxyalkyl" refers to an alkyl group as defined herein substituted with a hydroxy group.

[0057] The term "isomer" refers to compounds having the same molecular formula but different in the nature or order of bonding of their atoms or in the spatial arrangement of their atoms. Isomers that differ in the spatial arrangement of atoms are called "stereoisomers". Stereoisomers that are not mirror images of each other are called "diastereomers", and stereoisomers that are mirror images that cannot be superimposed on each other are called "enantiomers". When a compound has an asymmetric center, for example, when a compound is bonded to four different groups, a pair of enantiomers is possible. Enantiomers can be characterized by the absolute configuration of their asymmetric centers and are described by the Cahn and Prelog R and S sequence rules or in a manner in which the molecule rotates the plane of polarization and is designated as dextrorotatory or levorotatory (i.e., as the (+) or (-)-isomer, respectively). Chiral compounds can exist either as individual enantiomers or as mixtures thereof. A mixture containing enantiomers in the same proportion is called a "racemic mixture".

[0058] The terms "modulate", "modulation", or "modulating" refer to the biological activity of a compound or substrate that inhibits and / or activates PI3K.

[0059] The terms "patient" or "subject" are mammals such as humans, mice, rats, guinea pigs, dogs, cats, horses, cows, pigs, or non-human primates such as monkeys, chimpanzees, baboons, or macaques. Preferably, the mammal is a human.

[0060] The term "therapeutically effective amount" when used in connection with a compound refers to the amount or dosage of a compound that, upon single or multiple dose administration to a patient, results in the desired effect in a patient being diagnosed or treated. The effective amount can be determined by one of ordinary skill in the art using known techniques and observing the results obtained under similar circumstances. When determining the effective amount for a patient, several factors are considered including, but not limited to, the species of the patient; its size, age, and general health; the particular disease or disorder involved; the degree or involvement or severity of the disease or disorder; the response of the individual patient; the particular compound being administered; the mode of administration, the bioavailability characteristics of the formulation being administered, the dosing regimen selected; the use of concomitant medications; and other relevant circumstances.

[0061] The term "treating" with respect to a subject includes suppressing, slowing, halting, or reversing the progression or severity of an existing symptom or disorder.

[0062] The compounds of the present invention In one aspect, the present invention provides a compound of formula (I), or a pharmaceutically acceptable salt thereof,

Chemical formula

[0063] In a further aspect, a compound of formula (I) wherein R8 is H has formula (II), or a pharmaceutically acceptable salt thereof, [Chemical Formula] wherein R, R1, R2, R3, R4, R5, R6, and R7 are as defined in summary for formula (I).

[0064] In a compound of formula (I), or a pharmaceutically acceptable salt thereof, R is -H or C1-C3, R1 is of the formula: [Chemical Formula] is a group of R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxin, isoindolin-1-one, indolin-2-one, benzo[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine, or an optionally substituted bicyclic heteroaryl having 8 to 10 ring atoms containing 1, 2, 3, 4, or 5 ring heteroatoms independently selected from N, O, or S; the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from halogen and C1-C6 alkyl; the optionally substituted bicyclic heteroaryl is -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -SO2R 10 , -CONR 10 R 10 , -NR 10 R 10 , -NR 10 CO2R 10, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted heterocyclic ring selected from, optionally substituted phenyl, optionally substituted 1,3-benzodioxole, optionally substituted 2,3-dihydro-1,4-benzodioxin, or pyridine, pyrimidine, pyridazine, pyrazine, pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, an optionally substituted heteroaryl selected from, each independently selected from 1 to 3 substituents, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, or optionally substituted C2-C6 alkynyl is each, -CN, -OH, oxetanyl, or optionally substituted with C1-C3 alkoxy, optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted 1,3-benzodioxole, optionally substituted 2,3-dihydro-1,4-benzodioxin, optionally substituted heterocyclic ring, or optionally substituted heteroaryl is each, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -SO2R 10 , -NR 10 R 10 , -OH, or -CN, each independently selected from 1 to 3 substituents, optionally substituted with R3 is, -H, halogen, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C3-C5 cycloalkyl, a heterocyclic ring having 3 to 5 ring atoms containing 1, 2, or 3 ring heteroatoms independently selected from N, O, or S, or a heteroaryl having 5 ring atoms containing 1, 2, or 3 ring heteroatoms independently selected from N, O, or S, R4, R5, and R6 are each independently, -H, halogen, C1-C6 alkyl, or C1-C6 haloalkyl, R7 is -CN, C1-C6 alkyl, or C1-C6 haloalkyl, R8 is -H or C1-C6 alkyl, Each R9 is independently -H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C3-C5 cycloalkyl, R 10 is each independently -H or C1-C3 alkyl.

[0065] In the compound of formula (I), or a pharmaceutically acceptable salt thereof, R is -H or C1-C3, R1 is of the formula:

Chemical formula

[0066] In the compound of formula (I), or a pharmaceutically acceptable salt thereof, R is -H or C1-C3, R1 is of the formula:

Chemical formula

[0067] In the compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine, or an optionally substituted bicyclic heteroaryl having 8 to 10 ring atoms containing 1, 2, 3, 4, or 5 ring heteroatoms independently selected from N, O, or S, the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from halogen and C1-C6 alkyl, and the optionally substituted bicyclic heteroaryl is -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -SO2R 10 , -CONR 10 R 10 , -NR 10 R 10 , -NR 10 CO2R 10, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted heterocycle selected from, optionally substituted phenyl, optionally substituted 1,3-benzodioxole, optionally substituted 2,3-dihydro-1,4-benzodioxin, or pyridine, pyrimidine, pyridazine, pyrazine, pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, each independently selected from 1 to 3 substituents selected from optionally substituted heteroaryl, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, or optionally substituted C2-C6 alkynyl is each optionally substituted with -CN, -OH, oxetanyl, or C1-C3 alkoxy, optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted 1,3-benzodioxole, optionally substituted 2,3-dihydro-1,4-benzodioxin, optionally substituted heterocycle, or optionally substituted heteroaryl is each independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -SO2R 10 , -NR 10 R 10 , -OH, or -CN, each independently selected from 1 to 3 substituents optionally substituted with.

[0068] In the compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one, or an optionally substituted bicyclic heteroaryl having 8 - 10 ring atoms containing 1, 2, 3, 4, or 5 ring heteroatoms independently selected from N, O, or S, the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, the optionally substituted bicyclic heteroaryl is - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, - SO2R 10 、 - CONR 10 R 10 、 - NR 10 R 10 、 - NR 10 CO2R 10 、an optionally substituted C1 - C6 alkyl, an optionally substituted C3 - C5 cycloalkyl, an optionally substituted heterocyclic ring selected from pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl is optionally substituted with 1 - 3 substituents each independently selected from - CN, - OH, or C1 - C3 alkoxy, the optionally substituted C3 - C5 cycloalkyl, the optionally substituted phenyl, the optionally substituted heterocyclic ring, or the optionally substituted heteroaryl is each optionally substituted with 1 - 3 substituents each independently selected from halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR 10 R 10 、 - OH, or - CN.

[0069] In the compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is optionally substituted bicyclic heteroaryl and optionally substituted bicyclic heteroaryl is phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring, and the optionally substituted bicyclic heteroaryl is -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -SO2R 10 , -C(O)OC1-C3 alkyl, -CONR 10 R 10 , -NR 10 R 10 , -NR 10 CO2R 10 , -OH, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted heterocycle selected from, optionally substituted phenyl, optionally substituted 1,3-benzodioxole, optionally substituted 2,3-dihydro-1,4-benzodioxin, or pyridine, pyrimidine, pyridazine, pyrazine, pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, optionally substituted heteroaryl selected from, each independently selected from 1-3 substituents, and optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, or optionally substituted C2-C6 alkynyl are each, -CN, -OH, oxetanyl, C1-C3 alkoxy, -CONR 10 R 10or optionally substituted phenyl, optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted 1,3-benzodioxole, optionally substituted 2,3-dihydro-1,4-benzodioxine, optionally substituted heterocycle, or optionally substituted heteroaryl is each optionally substituted with 1 to 3 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -SO2R 10 -NR 10 R 10 -OH, or -CN.

[0070] In the compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is optionally substituted bicyclic heteroaryl and optionally substituted bicyclic heteroaryl is phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring, and optionally substituted bicyclic heteroaryl is -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -SO2R 10 -CONR 10 R 10 -NR 10 R 10 -NR 10 CO2R 10, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted heterocyclic ring selected from, optionally substituted phenyl, optionally substituted 1,3-benzodioxole, optionally substituted 2,3-dihydro-1,4-benzodioxine, or pyridine, pyrimidine, pyridazine, pyrazine, pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, each independently selected from optionally substituted heteroaryl, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, or optionally substituted C2-C6 alkynyl is each optionally substituted with -CN, -OH, oxetanyl, or C1-C3 alkoxy, optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted 1,3-benzodioxole, optionally substituted 2,3-dihydro-1,4-benzodioxine, optionally substituted heterocyclic ring, or optionally substituted heteroaryl is each, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -SO2R 10 , -NR 10 R 10 , -OH, or -CN, each independently selected from 1 to 3 substituents, optionally substituted bicyclic heteroaryl is preferably, -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -SO2R 10 , -CONR 10 R 10 , -NR 10 R 10 , -NR 10 CO2R 10, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted heterocyclic ring selected from, optionally substituted phenyl, or pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, each independently selected from optionally substituted heteroaryl, optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy, optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl is each, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R 10 , -OH, or -CN, each independently selected from 1 to 3 substituents, optionally substituted.

[0071] In the compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from halogen and C1-C6 alkyl, the optionally substituted bicyclic heteroaryl is -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -SO2R 10 , -CONR 10 R 10, -NR 10 R 10 , -NR 10 CO2R 10 , optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted heterocyclic ring selected from, optionally substituted phenyl, or pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, each independently selected from optionally substituted heteroaryl, optionally substituted with 1-3 substituents each independently selected from -CN, -OH, or C1-C3 alkoxy, optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl is each, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R 10 , -OH, or -CN, optionally substituted with 1-3 substituents each independently selected from.

[0072] In the compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1-C6 alkyl, and the optionally substituted bicyclic heteroaryl is -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -SO2R 10 , -CONR 10 R 10 , -NR 10 R 10 , -NR 10 CO2R 10 , an optionally substituted heterocyclic ring selected from optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R 10optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0073] In the compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each optionally substituted with halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR 10 R 10 optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0074] In the compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, or benzod[d]oxazol - 2(3H) - one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is condensed with a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted heterocyclic ring, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, each independently selected from 1 to 3 substituents, the optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each optionally substituted with 1 to 3 substituents each independently selected from halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR 10 R 10 , - OH, or - CN.

[0075] In the compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, benzod[d]oxazol - 2(3H) - one, 1,3 - dihydro - 2H - pyrrolo[2,3 - b]pyridin - 2 - one, or 2,3 - dihydro - [1,4]dioxino[2,3 - b]pyridine, or an optionally substituted bicyclic heteroaryl selected from indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, quinazoline, naphthyridine, quinoline, or oxazolopyridine. The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, - SO2R 10 , - C(O)OC1 - C3 alkyl, - CONR 10 R 10 , - NR 10 R 10 , - NR 10 CO2R 10, -OH, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted heterocyclic ring selected from, an optionally substituted phenyl, an optionally substituted 1,3-benzodioxole, an optionally substituted 2,3-dihydro-1,4-benzodioxine, or an optionally substituted heteroaryl selected from pyridine, pyrimidine, pyridazine, pyrazine, pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, each independently selected from 1 to 3 substituents, and the optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, or optionally substituted C2-C6 alkynyl are each -CN, -OH, oxetanyl, C1-C3 alkoxy, -CONR 10 R 10 , or optionally substituted phenyl, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted 1,3-benzodioxole, optionally substituted 2,3-dihydro-1,4-benzodioxine, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each independently selected from 1 to 3 substituents selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -SO2R 10 , -NR 10 R 10 , -OH, or -CN.

[0076] In the compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, benzod[d]oxazol - 2(3H) - one, 1,3 - dihydro - 2H - pyrrolo[2,3 - b]pyridin - 2 - one, or 2,3 - dihydro - [1,4]dioxino[2,3 - b]pyridine, or an optionally substituted bicyclic heteroaryl selected from indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, quinazoline, or naphthyridine; the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl; the optionally substituted bicyclic heteroaryl is - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, - SO2R 10 , - CONR 10 R 10 , - NR 10 R 10 , - NR 10 CO2R 101 to 3 substituents each independently selected from optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine; an optionally substituted heterocyclic ring; optionally substituted phenyl; optionally substituted 1,3-benzodioxole; optionally substituted 2,3-dihydro-1,4-benzodioxin; or an optionally substituted heteroaryl selected from pyridine, pyrimidine, pyridazine, pyrazine, pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, wherein the optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, or optionally substituted C2-C6 alkynyl is each optionally substituted with -CN, -OH, oxetanyl, or C1-C3 alkoxy, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted 1,3-benzodioxole, optionally substituted 2,3-dihydro-1,4-benzodioxin, optionally substituted heterocyclic ring, or optionally substituted heteroaryl is each optionally substituted with 1 to 3 substituents each independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -SO2R 10 , -NR 10 R 10 , -OH, or -CN.

[0077] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, benzod[d]oxazol - 2(3H) - one, 1,3 - dihydro - 2H - pyrrolo[2,3 - b]pyridin - 2 - one, or 2,3 - dihydro - [1,4]dioxino[2,3 - b]pyridine, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline, wherein the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, wherein the optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR 10 R 10optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0078] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole, wherein the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or heteroaryl optionally selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, wherein the optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0079] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, or benzod[d]oxazol - 2(3H) - one, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, or phthalazine. The optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR 10 R 10 Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0080] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, benzod[d]oxazol - 2(3H) - one, 1,3 - dihydro - 2H - pyrrolo[2,3 - b]pyridin - 2 - one, or 2,3 - dihydro - [1,4]dioxino[2,3 - b]pyridine, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, quinazoline, or naphthyridine (preferably indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline). The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, - SO2R 10 , - CONR 10 R 10 , - NR 10 R 10 , - NR 10 CO2R 10, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted heterocyclic ring selected from, optionally substituted phenyl, optionally substituted 1,3-benzodioxole, optionally substituted 2,3-dihydro-1,4-benzodioxine, or pyridine, pyrimidine, pyridazine, pyrazine, pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, an optionally substituted heteroaryl selected from each independently selected from 1 to 3 substituents optionally substituted, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, or optionally substituted C2-C6 alkynyl are each, -CN, -OH, oxetanyl, or optionally substituted with C1-C3 alkoxy, optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted 1,3-benzodioxole, optionally substituted 2,3-dihydro-1,4-benzodioxine, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -SO2R 10 , -NR 10 R 10 , -OH, or -CN, each independently selected from 1 to 3 substituents optionally substituted, preferably, the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from halogen and C1-C6 alkyl, optionally substituted bicyclic heteroaryl is, -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, -OH or oxetanyl optionally substituted C1-C6 alkyl, or pyridine or oxazole, an optionally substituted heteroaryl selected from each independently selected from 1 to 3 substituents optionally substituted.

[0081] In still further embodiments of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, benzod[d]oxazol - 2(3H) - one, 1,3 - dihydro - 2H - pyrrolo[2,3 - b]pyridin - 2 - one, or 2,3 - dihydro - [1,4]dioxino[2,3 - b]pyridine, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolo[2,3 - b]pyridine, pyrrolo[3,2 - b]pyridine, furo[2,3 - c]pyridine, furo[3,2 - c]pyridine, pyrazolo[1,5 - a]pyridine, pyrazolo[3,4 - b]pyridine, pyrazolo[3,4 - c]pyridine, pyrazolo[4,3 - b]pyridine, imidazo[1,2 - a]pyridine, imidazo[1,5 - a]pyridine, pyrazolo[1,5 - a]pyrimidine, imidazo[1,2 - b]pyridazine, phthalazine, [1,2,4]triazolo[4,3 - a]pyridine, triazolo[1,5 - a]pyridine, benzimidazole, pyrrolo[2,3 - d]pyrimidine, thiazolo[5,4 - b]pyridine, benzotriazole, 1,3 - benzoxazole, 1,3 - benzothiazole, pyrrolo[1,2 - a]pyrazine, quinazoline, 1,5 - naphthyridine, 1,7 - naphthyridine, quinoline, or oxazolo[5,4 - b]pyridine. The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, - SO2R 10 、 - C(O)OC1 - C3 alkyl, - CONR 10 R 10 、 - NR 10 R 10 、 - NR 10 CO2R 10, -OH, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted heterocyclic ring selected from, optionally substituted phenyl, optionally substituted 1,3-benzodioxole, optionally substituted 2,3-dihydro-1,4-benzodioxin, or an optionally substituted heteroaryl selected from pyridine, pyrimidine, pyridazine, pyrazine, pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, each independently selected from 1 to 3 substituents, and optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, or optionally substituted C2-C6 alkynyl are each, -CN, -OH, oxetanyl, C1-C3 alkoxy, -CONR 10 R 10 , or optionally substituted phenyl, and optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted 1,3-benzodioxole, optionally substituted 2,3-dihydro-1,4-benzodioxin, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -SO2R 10 , -NR 10 R 10 , -OH, or -CN, each independently selected from 1 to 3 substituents, and is optionally substituted.

[0082] In a further embodiment of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, benzod[d]oxazol - 2(3H) - one, 1,3 - dihydro - 2H - pyrrolo[2,3 - b]pyridin - 2 - one, or 2,3 - dihydro - [1,4]dioxino[2,3 - b]pyridine, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolo[2,3 - b]pyridine, pyrrolo[3,2 - b]pyridine, furo[2,3 - c]pyridine, furo[3,2 - c]pyridine, pyrazolo[1,5 - a]pyridine, pyrazolo[3,4 - b]pyridine, pyrazolo[3,4 - c]pyridine, pyrazolo[4,3 - b]pyridine, imidazo[1,2 - a]pyridine, imidazo[1,5 - a]pyridine, pyrazolo[1,5 - a]pyrimidine, imidazo[1,2 - b]pyridazine, phthalazine, [1,2,4]triazolo[4,3 - a]pyridine, triazolo[1,5 - a]pyridine, benzimidazole, pyrrolo[2,3 - d]pyrimidine, thiazolo[5,4 - b]pyridine, benzotriazole, 1,3 - benzoxazole, 1,3 - benzothiazole, pyrrolo[1,2 - a]pyrazine, quinazoline, or 1,7 - naphthyridine. The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, - SO2R 10 , - CONR 10 R 10 , - NR 10 R 10 , - NR 10 CO2R 10, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted heterocyclic ring selected from, optionally substituted phenyl, optionally substituted 1,3-benzodioxole, optionally substituted 2,3-dihydro-1,4-benzodioxin, or pyridine, pyrimidine, pyridazine, pyrazine, pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, each independently selected from optionally substituted heteroaryl, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, or optionally substituted C2-C6 alkynyl is each optionally substituted with -CN, -OH, oxetanyl, or C1-C3 alkoxy, optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted 1,3-benzodioxole, optionally substituted 2,3-dihydro-1,4-benzodioxin, optionally substituted heterocyclic ring, or optionally substituted heteroaryl is each optionally substituted with 1-3 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -SO2R 10 , -NR 10 R 10 , -OH, or -CN, each independently selected from 1-3 substituents, and preferably, the optionally substituted bicyclic ring is optionally substituted with 1-3 substituents independently selected from halogen and C1-C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, -OH or oxetanyl-substituted C1-C6 alkyl, or pyridine or oxazole, each independently selected from heteroaryl, optionally substituted with 1-3 substituents.

[0083] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is a group of the formula:

Chem.

Chem.

Chem.

Chem.

[0084] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is a group of the formula:

Chem.

Chem.

Chem.

Chem.

[0085] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, halogen, -CN, -N(H)(CH2CH2CO2H), -C(O)C1-C3 alkyl, C1-C6 alkyl, C1-C6 haloalkyl, oxetane, isoxazole, or pyridine (preferably 3-pyridine). In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, halogen, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C3-C5 cycloalkyl, a heterocyclic ring having 3-5 ring atoms containing 1, 2, or 3 ring heteroatoms independently selected from N, O, or S, or a heteroaryl having 5 ring atoms containing 1, 2, or 3 ring heteroatoms independently selected from N, O, or S. In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, halogen, -CN, C1-C6 alkyl, C1-C6 haloalkyl, oxetane, or isoxazole. In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, C1-C6 alkyl, or C1-C6 haloalkyl, preferably, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl, more preferably, R3 is -H, -CN, or C1-C3 alkyl, most preferably, R3 is -H or methyl. Similarly preferably, R3 is -H, methyl, or trifluoromethyl.

[0086] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R4 is H or halogen, preferably, R4 is -H.

[0087] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, more preferably, R5 is -H, halogen, methyl, or trifluoromethyl.

[0088] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R6 is -H or halogen.

[0089] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H)-one), or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring being optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl being optionally substituted with 1 - 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl being optionally substituted with -CN, -OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl each being optionally substituted with 1 - 3 substituents each independently selected from halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR, 10 R 10 , -OH, or -CN.

[0090] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1-C6 alkyl, and the optionally substituted bicyclic heteroaryl is -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted heterocyclic ring, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, each independently selected from 1 to 3 substituents, the optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each optionally substituted with 1 to 3 substituents each independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R 10 , -OH, or -CN.

[0091] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, methyl, or trifluoromethyl (preferably, R3 is -H or methyl), and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole). The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0092] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R3 is -H, methyl, or trifluoromethyl (preferably, R3 is -H or methyl), R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, or benzod[d]oxazol - 2(3H) - one, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, or phthalazine. The optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each, halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR 10 R 10 Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0093] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R4 is -H or halogen (preferably, R4 is -H), and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H)-one), or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each optionally substituted with 1 - 3 substituents each independently selected from halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR, 10 R 10 , -OH, or -CN.

[0094] In the compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R4 is -H or halogen (preferably, R4 is -H), R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, or benzod[d]oxazol - 2(3H) - one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is condensed with a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl is each optionally substituted with 1 - 3 substituents each independently selected from halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR 10 R 10 , -OH, or -CN.

[0095] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R4 is -H or halogen (preferably, R4 is -H), and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H)-one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably, indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole). The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl are each, halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0096] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R4 is -H or halogen (preferably, R4 is -H), and R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxin, isoindolin - 1 - one, or benzod[d]oxazol - 2(3H)-one, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, or phthalazine. The optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl is each, halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR 10 R 10 Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0097] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each optionally substituted with 1 - 3 substituents each independently selected from halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10 , - OH, or - CN.

[0098] In the compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, and R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is condensed with a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1-3 substituents each independently selected from C1-C6 alkyl, and the optionally substituted bicyclic heteroaryl is -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, a heterocyclic ring optionally substituted with pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted phenyl, or a heteroaryl optionally substituted with pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, each independently selected from 1-3 substituents, the optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each optionally substituted with 1-3 substituents each independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R 10 , -OH, or -CN.

[0099] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R5 is -H, halogen, methyl, or trifluoromethyl, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole). The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0100] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R5 is -H, halogen, methyl, or trifluoromethyl, and R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, or benzod[d]oxazol - 2(3H) - one, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, or phthalazine. The optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each optionally substituted with halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR 10 R 10 Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0101] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R6 is -H or halogen, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring being optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl being optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl being optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl each being optionally substituted with 1 - 3 substituents each independently selected from halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10 , - OH, or - CN.

[0102] In the compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R6 is -H or halogen, and R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is condensed with a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring). The optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1-C6 alkyl, and the optionally substituted bicyclic heteroaryl is -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, an optionally substituted heterocyclic ring selected from pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, and is optionally substituted with 1 to 3 substituents each independently selected therefrom. The optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl is each optionally substituted with 1 to 3 substituents each independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R 10 , -OH, or -CN.

[0103] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R6 is -H or halogen, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzo[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H)-one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole). The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl is each, halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0104] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R6 is -H or halogen, and R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, or benzod[d]oxazol - 2(3H)-one, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, or phthalazine. The optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each optionally substituted with halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR 10 R 10 Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0105] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl, R4 is H or halogen, more preferably, R3 is -H, -CN, or C1-C3 alkyl, R4 is H, most preferably, R3 is -H or methyl, and R4 is -H.

[0106] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, more preferably, R3 is -H or methyl, and R5 is -H, halogen, methyl, or trifluoromethyl.

[0107] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R6 is -H or halogen, more preferably, R3 is -H or methyl, and R6 is -H or halogen.

[0108] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R4 is -H or halogen (preferably, R4 is -H), R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, preferably, R5 is -H, halogen, methyl, or trifluoromethyl.

[0109] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R4 is -H or halogen (preferably, R4 is -H), R6 is -H or halogen.

[0110] In still further compounds of formula (I) or (II), or pharmaceutically acceptable salts thereof, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, R6 is -H or halogen, preferably, R5 is -H, halogen, methyl, or trifluoromethyl, and R6 is -H.

[0111] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R4 is -H or halogen (preferably, R4 is -H), and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, preferably, R3 is -H or methyl, R4 is -H, and R2 is 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxin, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H)-one, 1,3 - dihydro - 2H - pyrrolo[2,3 - b]pyridin - 2 - one, or 2,3 - dihydro - [1,4]dioxino[2,3 - b]pyridine (preferably, 1,3 - benzodioxole, 2,3 - dihydro - 1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole). The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl is each, halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10It is optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0112] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R4 is -H or halogen (preferably, R4 is -H), R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1-C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl are each halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, preferably, R3 is -H or methyl, R4 is -H, and R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, or benzod[d]oxazol - 2(3H)-one, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, or phthalazine. The optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR 10 R 10 Optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN.

[0113] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring being optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl being optionally substituted with 1 - 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl being optionally substituted with -CN, -OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl each being halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, preferably, R3 is -H or methyl, R5 is -H, halogen, methyl, or trifluoromethyl, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole). The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0114] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1-C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl are each halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R10 Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN. Preferably, R3 is -H or methyl, R5 is -H, halogen, methyl, or trifluoromethyl, and R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, or phthalazine. The optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1-C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or heteroaryl optionally substituted with 1 to 3 substituents each independently selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy. The optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each optionally substituted with halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R 10 Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0115] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R6 is -H or halogen, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, preferably, R3 is -H or methyl, R6 is -H, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzo[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole). The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10is optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0116] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R6 is -H or halogen, R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1-C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, a heterocyclic ring optionally substituted with pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted phenyl, or a heteroaryl optionally substituted with pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR10 R 10 is optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, preferably, R3 is -H or methyl, R6 is -H, R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, or benzod[d]oxazol - 2(3H) - one, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, or phthalazine. The optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted heterocyclic ring, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, each independently selected from 1 to 3 substituents. The optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR 10 R 10 is optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN.

[0117] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R4 is -H or halogen (preferably, R4 is -H), R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4-benzodioxine, isoindolin-1-one, indolin-2-one, or benzod[d]oxazol-2(3H)-one), or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring being optionally substituted with 1 to 3 substituents each independently selected from halogen and C1-C6 alkyl, and the optionally substituted bicyclic heteroaryl being optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1-C6 alkyl being optionally substituted with -CN, -OH, or C1-C3 alkoxy, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl each being halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, preferably, R5 is -H, halogen, methyl, or trifluoromethyl, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole), wherein the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, wherein the optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0118] In the compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R4 is -H or halogen (preferably, R4 is -H), R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxin, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is condensed with a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1-C6 alkyl, the optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN. Preferably, R5 is -H, halogen, methyl, or trifluoromethyl. R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, or benzod[d]oxazol - 2(3H) - one, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, or phthalazine. The optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR 10 R 10 Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0119] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R4 is -H or halogen (preferably, R4 is -H), R6 is -H or halogen, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring being optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl being optionally substituted with 1 - 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl being optionally substituted with -CN, -OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl each being halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR, 10 R 10、 -OH, or -CN, and is optionally substituted with 1 to 3 substituents independently selected from each, preferably, R4 and R6 are each -H, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole). The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl is each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0120] In the compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R4 is -H or halogen (preferably, R4 is -H), R6 is -H or halogen, R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, or benzod[d]oxazol - 2(3H) - one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is condensed with a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR 10 R 10、 -OH, or -CN, and is optionally substituted with 1 to 3 substituents independently selected from each, preferably, R4 and R6 are each -H, and R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxin, isoindolin - 1 - one, or benzod[d]oxazol - 2(3H)-one, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, or phthalazine. The optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents independently selected from C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR 10 R 10 , -OH, or -CN, and is optionally substituted with 1 to 3 substituents independently selected from each.

[0121] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, R6 is -H or halogen, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring being optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl being optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl being optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl each being halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, preferably, R5 is -H, halogen, methyl, or trifluoromethyl, R6 is -H, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H)-one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole). The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0122] In the compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl; R6 is -H or halogen; R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring). The optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1-C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy. The optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl is each halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN. Preferably, R5 is -H, halogen, methyl, or trifluoromethyl; R6 is -H; R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxin, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, or phthalazine. The optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1-C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or heteroaryl optionally substituted with 1 to 3 substituents each independently selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy. The optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl is each substituted with halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R 10 Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0123] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R4 is -H or halogen (preferably, R4 is -H), R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, more preferably, R3 is -H or methyl, R4 is -H, and R5 is -H, halogen, methyl, or trifluoromethyl.

[0124] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R4 is -H or halogen (more preferably, R4 is -H), R6 is -H or halogen, more preferably, R3 is -H or methyl, and R4 and R6 are each -H.

[0125] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, R6 is -H or halogen, more preferably, R3 is -H or methyl, R5 is -H, halogen, methyl, or trifluoromethyl, and R6 is -H.

[0126] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, R4 is -H or halogen (preferably, R4 is -H), R6 is -H or halogen, preferably, R5 is -H, halogen, methyl, or trifluoromethyl, and R4 and R6 are each -H.

[0127] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R4 is -H or halogen (preferably, R4 is -H), and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring being optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl being optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl being optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl each being halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, preferably, R3 is -H or methyl, R4 is -H, R5 is -H, halogen, methyl, or trifluoromethyl, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H)-one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole), wherein the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, wherein the optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR, 10 R 10It is optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0128] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R4 is -H or halogen (preferably, R4 is -H), R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1-C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl are each halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN. Preferably, R3 is -H or methyl, R4 is -H, R5 is -H, halogen, methyl, or trifluoromethyl, and R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, or phthalazine. The optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1-C6 alkyl, and the optionally substituted bicyclic heteroaryl is -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted heterocyclic ring, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, each independently selected from 1 to 3 substituents. The optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R 10 Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0129] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R4 is -H or halogen (preferably, R4 is -H), R6 is -H or halogen, R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring being optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl being optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl being optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl each being halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, preferably, R3 is -H or methyl, R4 and R6 are each -H, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole). The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl is each, halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10is optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0130] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R4 is -H or halogen (preferably, R4 is -H), R6 is -H or halogen, R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1-3 substituents each independently selected from C1-C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1-3 substituents each independently selected from -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl are each halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN. Preferably, R3 is -H or methyl, R4 and R6 are each -H, and R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, or phthalazine. The optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1-C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy. The optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl is each halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R 10 Optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0131] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R6 is -H or halogen, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, more preferably, R3 is -H or methyl, R5 is -H, halogen, methyl, or trifluoromethyl, R6 is -H, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole), wherein the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, wherein the optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0132] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R6 is -H or halogen, and R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1-C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, a heterocyclic ring optionally substituted with pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or a heteroaryl optionally substituted with pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR10 R 10 is optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, more preferably, R3 is -H or methyl, R5 is -H, halogen, methyl, or trifluoromethyl, R6 is -H, R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxin, isoindolin - 1 - one, or benzod[d]oxazol - 2(3H)-one, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, or phthalazine. The optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted heterocyclic ring, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, each independently selected from 1 to 3 substituents. The optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR 10 R 10 is optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN.

[0133] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, R4 is -H or halogen (preferably, R4 is -H), R6 is -H or halogen, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H)-one), or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring being optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl being optionally substituted with 1 - 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl being optionally substituted with -CN, -OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl each being halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN. Preferably, R5 is -H, halogen, methyl, or trifluoromethyl, R4 is -H, R6 is -H or halogen, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzo[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole). The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0134] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, R4 is -H or halogen (preferably, R4 is -H), R6 is -H or halogen, R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1-C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR10 R 10 is optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, preferably, R5 is -H, halogen, methyl, or trifluoromethyl, R4 is -H, R6 is -H or halogen, R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxin, isoindolin - 1 - one, or benzod[d]oxazol - 2(3H)-one, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, or phthalazine, the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1 - C6 alkyl, the optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy, the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR 10 R 10 is optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN.

[0135] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R4 is -H or halogen (preferably, R4 is -H), R6 is -H or halogen, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, preferably, R3 is -H or methyl, R4 and R6 are each -H, and R5 is -H, halogen, methyl, or trifluoromethyl.

[0136] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R4 is -H or halogen (preferably, R4 is -H), R6 is -H or halogen, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, more preferably, R3 is -H or methyl, R4 is -H, R6 is -H or halogen, R5 is -H, halogen, methyl, or trifluoromethyl, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole). The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10It is optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0137] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R4 is -H or halogen (preferably, R4 is -H), R6 is -H or halogen, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1-3 substituents each independently selected from C1-C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1-3 substituents each independently selected from -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl are each halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10R 10 [, -OH, or -CN, and is optionally substituted with 1 to 3 substituents independently selected from each, more preferably, R3 is -H or methyl, R4 is -H, R6 is -H or halogen, R5 is -H, halogen, methyl, or trifluoromethyl, R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, or phthalazine. The optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents independently selected from C1-C6 alkyl, and the optionally substituted bicyclic heteroaryl is -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted heterocyclic ring, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, and is optionally substituted with 1 to 3 substituents independently selected from each. The optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl is each halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R 10 [, -OH, or -CN, and is optionally substituted with 1 to 3 substituents independently selected from each.]

[0138] ​​In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R is -H.

[0139] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R7 is -CN, C1-C3 alkyl, or C1-C3 haloalkyl, and more preferably, R7 is -CN, methyl, or trifluoromethyl.

[0140] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R8 is -H.

[0141] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R7 is -CN, C1-C3 alkyl, or C1-C3 haloalkyl and R is -H. In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R7 is C1-C3 alkyl (preferably methyl) and R is -H.

[0142] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R8 and R are each -H.

[0143] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R7 is -CN, C1-C3 alkyl, or C1-C3 haloalkyl and R8 is -H. In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R7 is C1-C3 alkyl (preferably methyl) and R8 is -H.

[0144] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R7 is -CN, C1-C3 alkyl, or C1-C3 haloalkyl, and R8 and R are each -H. In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R7 is C1-C3 alkyl (preferably methyl), and R8 and R are each -H.

[0145] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R7 is -CN, C1-C3 alkyl, or C1-C3 haloalkyl, R8 is -H, R is -H, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring being optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl being optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl being optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl each being optionally substituted with 1 - 3 substituents each independently selected from halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10 , - OH, or - CN.

[0146] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R7 is -CN, C1-C3 alkyl, or C1-C3 haloalkyl, R8 is -H, R is -H, R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxin, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1-C6 alkyl, and the optionally substituted bicyclic heteroaryl is -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted heterocyclic ring, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, each independently selected from 1 to 3 substituents, and the optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each optionally substituted with 1 to 3 substituents each independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R 10 , -OH, or -CN.

[0147] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R7 is C1-C3 alkyl (preferably methyl), R8 is -H, R is -H, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably, indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole). The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted heterocyclic ring, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0148] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R7 is C1-C3 alkyl (preferably methyl), R8 is -H, R is -H, R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxin, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, or phthalazine; the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1-C6 alkyl; the optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole; the optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy; and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each optionally substituted with halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R 10 optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0149] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R7 is -CN, C1-C3 alkyl, or C1-C3 haloalkyl, and R8 and R are each -H. In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H or methyl, R7 is C1-C3 alkyl (preferably methyl), and R8 and R are each -H.

[0150] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R7 is -CN, C1-C3 alkyl, or C1-C3 haloalkyl, and R4, R8, and R are each -H. In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R7 is C1-C3 alkyl (preferably methyl), and R4, R8, and R are each -H.

[0151] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, R7 is -CN, methyl, or trifluoromethyl, and R8 and R are each -H. In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R5 is -H, halogen, methyl, or trifluoromethyl, R7 is methyl, and R8 and R are each -H.

[0152] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R4 is -H or halogen (preferably, R4 is -H), R6 is -H or halogen, R7 is -CN, methyl, or trifluoromethyl, R8 is -H, R is -H, R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably, 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, preferably, R3 is -H or methyl, R4 is -H, R6 is -H or halogen, R5 is -H, halogen, methyl, or trifluoromethyl, R7 is methyl, R8 is -H, R is -H, R2 is 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxin, isoindolin - 1 - one, indolin - 2 - one, benzod[d]oxazol - 2(3H)-one, 1,3 - dihydro - 2H - pyrrolo[2,3 - b]pyridin - 2 - one, or 2,3 - dihydro - [1,4]dioxino[2,3 - b]pyridine (preferably, 1,3 - benzodioxole, 2,3 - dihydro - 1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole). The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10is optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0153] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl (preferably, R3 is -H, -CN, or C1-C3 alkyl), R4 is -H or halogen (preferably, R4 is -H), R6 is -H or halogen, R7 is -CN, methyl, or trifluoromethyl, R8 is -H, R is -H, R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1-C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy, and the optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl are each halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR10 R 10 is optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN. Preferably, R3 is -H or methyl, R4 is -H, R6 is -H or halogen, R5 is -H, halogen, methyl, or trifluoromethyl, R7 is methyl, R8 is -H, R is -H, R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, or benzod[d]oxazol-2(3H)-one, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, or phthalazine. The optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C1-C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents each independently selected from -CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1-C6 alkyl is optionally substituted with -CN, -OH, or C1-C3 alkoxy. The optionally substituted C3-C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, -NR 10 R 10 and is optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN.

[0154] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, each R9 is independently -H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C3-C5 cycloalkyl. In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, each R9 is independently -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, and preferably each R9 is independently -H, halogen, methyl, or trifluoromethyl.

[0155] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R1 is of the formula:

Chemical formula

[0156] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R1 is of the formula:

Chemical formula

[0157] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R1 is of the formula:

Chemical formula

[0158] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0159] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula

Chemical formula

[0160] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula

Chemical formula

[0161] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0162] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0163] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0164] In an even further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0165] In an even further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0166] In an even further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0167] In an even further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0168] In an even further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0169] In an even further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0170] In an even further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0171] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl, R4 is -H or halogen, R6 is -H or halogen, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, and R1 is a group of the formula:

Chemical formula

[0172] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, or C1-C3 alkyl, R4 is -H, R6 is -H or halogen, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, and R1 is a group of the formula:

Chemical formula

[0173] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R7 is -CN, methyl, or trifluoromethyl, R8 and R are each -H, and R1 is a group of the formula: [Chemical] is a group of the formula, where each R9 is independently -H, halogen, C1-C3 alkyl, C1-C3 haloalkyl, or C3-C5 cycloalkyl; more preferably, R7 is methyl, R8 and R are each -H, and each R9 is independently -H, halogen, methyl, trifluoromethyl, or cyclopropyl.

[0174] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R7 is -CN, methyl, or trifluoromethyl, R8 and R are each -H, and R1 is of the formula: [Chemical] is a group of the formula, where each R9 is independently -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl; more preferably, R7 is methyl, R8 and R are each -H, and each R9 is independently -H, halogen, methyl, or trifluoromethyl.

[0175] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl, R4 is -H or halogen, R8 and R are each -H, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, R6 is -H or halogen, R7 is -CN, methyl, or trifluoromethyl, and R1 is of the formula: [Chemical] is a group, wherein each R9 is independently -H, halogen, C1-C3 alkyl, C1-C3 haloalkyl, or C3-C5 cycloalkyl, more preferably, R3 is -H, methyl, or trifluoromethyl; R4 is -H or halogen; R6 is -H or halogen; R8 and R are each -H; R5 is -H, halogen, methyl, or trifluoromethyl; R7 is methyl; and each R9 is independently -H, halogen, methyl, trifluoromethyl, or cyclopropyl.

[0176] In an even further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, or C1-C3 alkyl; R4, R8, and R are each -H; R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl; R6 is -H or halogen; R7 is -CN, methyl, or trifluoromethyl; and R1 is of the formula:

Chemical formula

[0177] In an even further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl; R4 is -H or halogen; R8 and R are each -H; R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl; R6 is -H or halogen; R7 is -CN, methyl, or trifluoromethyl; and R1 is of the formula:

Chemical formula

[0178] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, or C1-C3 alkyl; R4, R8, and R are each -H; R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl; R6 is -H or halogen; R7 is -CN, methyl, or trifluoromethyl; and R1 is a group of the formula:

Chemical formula

[0179] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, or C1-C3 alkyl; R4, R8, and R are each -H; R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl; R6 is -H or halogen; R7 is -CN, methyl, or trifluoromethyl; and R1 is a group of the formula:

Chemical formula

[0180] In an even further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl, R4 is -H or halogen, R8 and R are each -H, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, R6 is -H or halogen, R7 is -CN, methyl, or trifluoromethyl, and R1 is of the formula:

Chemical formula

[0181] In an even further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, or C1-C3 alkyl, R4, R8, and R are each -H, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, R6 is -H or halogen, R7 is -CN, methyl, or trifluoromethyl, and R1 is of the formula:

Chemical formula

[0182] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, or C1-C3 alkyl, R4, R8, and R are each -H, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, R6 is -H or halogen, R7 is -CN, methyl, or trifluoromethyl, and R1 is of the formula:

Chemical formula

[0183] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl, R4 is -H or halogen, R8 and R are each -H, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, R6 is -H or halogen, R7 is -CN, methyl, or trifluoromethyl, and R1 is of the formula:

Chemical formula

[0184] In an additional compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0185] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R1 is of the formula:

Chemical formula

[0186] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 has the formula:

Chemical formula

[0187] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R1 is of the formula:

Chemical formula

[0188] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R1 is of the formula:

Chemical formula

[0189] In an additional compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula: [Chemical formula] is a group, wherein R9 is -H, halogen, or C1-C3 haloalkyl, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H)-one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole). The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each, halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR, 10 R 10is optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN. Preferably, R9 is -H or halogen.

[0190] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R1 is of the formula:

Chemical formula

[0191] In an additional compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0192] In an even further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula: [Chemical] is a group, wherein R9 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H)-one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole). The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from -CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with -CN, -OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, -NR, 10 R 10optionally substituted with 1 to 3 substituents each independently selected from -OH or -CN.

[0193] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0194] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R1 is of the formula:

Chemical formula

[0195] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzo[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each independently optionally substituted with 1 - 3 substituents each independently selected from halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10 , - OH, or - CN, the optionally substituted C1 - C6 alkyl is optionally substituted with 1 - 3 substituents each independently selected from - CN, - OH, or C1 - C3 alkoxy, R3 is - H, - CN, C1 - C3 alkyl, or C1 - C3 haloalkyl, R4 is - H or halogen, R6 is - H or halogen, R5 is - H, halogen, C1 - C3 alkyl, or C1 - C3 haloalkyl, and R1 is of the formula:

Chemical formula

[0196] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, or benzod[d]oxazol - 2(3H) - one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted heterocyclic ring, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, and is optionally substituted with 1 - 3 substituents each independently selected therefrom, the optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each independently optionally substituted with 1 - 3 substituents each independently selected from halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR 10 R 10 , - OH, or - CN, R3 is - H, - CN, or C1 - C3 alkyl, R4 is - H, R6 is - H or halogen, R5 is - H, halogen, C1 - C3 alkyl, or C1 - C3 haloalkyl, and R1 is of the formula: [Chemical formula] is a group, wherein each R9 is independently -H, halogen, or C1-C3 haloalkyl. Preferably, R3 is -H or methyl, each of R4 and R6 is -H, R5 is -H, halogen, methyl, or trifluoromethyl, and each R9 is independently -H, halogen, methyl, or trifluoromethyl.

[0197] In still further compounds of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, benz[d]oxazol - 2(3H) - one, 1,3 - dihydro - 2H - pyrrolo[2,3 - b]pyridin - 2 - one, or 2,3 - dihydro - [1,4]dioxino[2,3 - b]pyridine (preferably 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benz[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycle, or optionally substituted heteroaryl are each halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR10 R 10 is optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, R7 is -CN, methyl, or trifluoromethyl, R8 and R are each -H, and R1 is of the formula:

Chemical formula

[0198] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, or benzod[d]oxazol - 2(3H) - one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is condensed with a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted heterocyclic ring, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, each independently selected from 1 - 3 substituents, the optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each optionally substituted with 1 - 3 substituents each independently selected from halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR 10 R 10 , - OH, or - CN, each independently selected from 1 - 3 substituents, R7 is - CN, methyl, or trifluoromethyl, R8 and R are each - H, and R1 is of the formula:

Chemical formula

[0199] In an additional compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0200] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 has the formula:

Chemical formula

[0201] In an additional compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 has the formula:

Chemical formula

[0202] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R1 is of the formula:

Chemical formula

[0203] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R1 has the formula:

Chemical formula

[0204] In an additional compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0205] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R1 is of the formula:

Chemical formula

[0206] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R1 is of the formula:

Chemical formula

[0207] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R1 is of the formula:

Chem.

[0208] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each independently halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, R3 is -H, -CN, C1-C3 alkyl, or C1-C3 haloalkyl, R4 is -H or halogen, R8 and R are each -H, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, R6 is -H or halogen, R7 is -CN, methyl, or trifluoromethyl, and R1 is of the formula: [Chemical formula: wherein each R9 is independently -H, halogen, methyl, C1-C3 haloalkyl, or cyclopropyl.

[0209] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R2 is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, or benzod[d]oxazol - 2(3H) - one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is condensed with a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from C1 - C6 alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, the optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy, and the optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each independently halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, R3 is -H, -CN, or C1-C3 alkyl, R4, R8, and R are each -H, R5 is -H, halogen, C1-C3 alkyl, or C1-C3 haloalkyl, R6 is -H or halogen, R7 is -CN, methyl, or trifluoromethyl, and R1 is of the formula: [Chemical formula] a group of, wherein each R9 is independently -H, halogen, methyl, or C1-C3 haloalkyl.

[0210] In an additional compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula: [Chemical formula] is a group, wherein each R9 is independently -H, halogen, methyl, or trifluoromethyl, and R2 is 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzod[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (preferably 1,3-benzodioxole, 2,3-dihydro-1,An optionally substituted bicyclic ring selected from 4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one), or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, or quinazoline (preferably indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, or triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, or benzoxazole). The optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents each independently selected from halogen and C1 - C6 alkyl. The optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents each independently selected from - CN, halogen, C1 - C6 haloalkyl, C1 - C6 alkoxy, C1 - C6 haloalkoxy, optionally substituted C1 - C6 alkyl, optionally substituted C3 - C5 cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, or optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole. The optionally substituted C1 - C6 alkyl is optionally substituted with - CN, - OH, or C1 - C3 alkoxy. The optionally substituted C3 - C5 cycloalkyl, optionally substituted phenyl, optionally substituted heterocyclic ring, or optionally substituted heteroaryl are each independently halogen, C1 - C3 alkyl, C1 - C3 haloalkyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy, - NR, 10 R 10Optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, R3 is -H, methyl, or trifluoromethyl, R4 is -H or halogen, R8 and R are each -H, R5 is -H, halogen, methyl, or trifluoromethyl, R6 is -H or halogen, and R7 is C1-C3 alkyl (preferably methyl).

[0211] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0212] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R1 is of the formula:

Chemical formula

[0213] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0214] In a still further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0215] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0216] In a further compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof, R1 is of the formula:

Chemical formula

[0217] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R1 is of the formula:

Chemical formula

[0218] In still further compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, R1 is of the f...

Claims

1. Formula: 【Chemical Formula 1】 [wherein, R is -H or C １ ~C ３ alkyl, and R １ is the formula: [Chemical 2] is a group of, R ２ is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, benzo[d]oxazol - 2(3H) - one, 1,3 - dihydro - 2H - pyrrolo[2,3 - b]pyridin - 2 - one, or 2,3 - dihydro - [1,4]dioxino[2,3 - b]pyridine, or an optionally substituted bicyclic heteroaryl, wherein the optionally substituted bicyclic heteroaryl is phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring condensed with a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring, and the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from halogen and C １ ~C ６ alkyl, and the optionally substituted bicyclic heteroaryl is - CN, halogen, C １ ~C ６ haloalkyl, C １ ~C ６ alkoxy, C １ ~C ６ haloalkoxy, - SO ２ R １０ , - C(O)OC １ ~C ３ alkyl, - CONR １０ R １０ , - NR １０ R １０ , - NR １０ CO ２ R １０ , - OH, optionally substituted C １ ~C ６ alkyl, optionally substituted C ２ ~C ６ alkenyl, optionally substituted C ２ ~C ６ alkynyl, optionally substituted C ３ ~C ５ Optionally substituted heterocycles independently selected from cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, optionally substituted 1,3-benzodioxole, optionally substituted 2,3-dihydro-1,4-benzodioxin, or optionally substituted heteroaryl selected from pyridine, pyrimidine, pyridazine, pyrazine, pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, optionally substituted with 1 to 3 substituents each independently selected from the group consisting of, said optionally substituted C １ -C ６ alkyl, said optionally substituted C ２ -C ６ alkenyl, or said optionally substituted C ２ -C ６ alkynyl, each of which is -CN, -OH, oxetanyl, C １ -C ３ alkoxy, -CONR １０ R １０ 、 or optionally substituted phenyl, said optionally substituted C ３ -C ５ cycloalkyl, said optionally substituted phenyl, said optionally substituted 1,3-benzodioxole, said optionally substituted 2,3-dihydro-1,4-benzodioxin, said optionally substituted heterocycle, or said optionally substituted heteroaryl, each of which is halogen, C １ -C ３ alkyl, C １ -C ３ haloalkyl, C １ -C ３ alkoxy, C １ -C ３ haloalkoxy, -SO ２ R １０ 、 -NR １０ R １０ 、 -OH, or -CN, optionally substituted with 1 to 3 substituents each independently selected from the group consisting of, R ３ is selected from -H, halogen, -CN, -N(H)(C １ to C ３ alkyl), -N(C １ to C ３ alkyl), ２ , -N(H)(CH ２ CH ２ CO ２ H), -C(O)C １ to C ３ alkyl, C １ to C ６ alkyl, C １ to C ６ haloalkyl, C １ to C ６ hydroxyalkyl, C ３ to C ５ cycloalkyl, a optionally substituted heterocyclic ring having 3 to 5 ring atoms containing 1, 2 or 3 ring heteroatoms independently selected from N, O or S, or a optionally substituted heteroaryl having 5 or 6 ring atoms containing 1, 2 or 3 ring heteroatoms independently selected from N, O or S, wherein the optionally substituted heterocyclic ring or the optionally substituted heteroaryl is each optionally substituted with 1 to 3 substituents independently selected from halogen, C １ to C ３ alkyl, or C １ to C ３ haloalkyl, R ４ , R ５ , and R ６ are each independently -H, halogen, C １ ~C ６ alkyl, or C １ ~C ６ haloalkyl, and R ７ is -CN, C １ ~C ６ alkyl, or C １ ~C ６ haloalkyl, and R ８ is -H or C １ ~C ６ alkyl, and R ９ is, independently of each other, -H, halogen, -CN, C １ to C ６ alkyl, C １ to C ６ haloalkyl, C １ to C ６ alkoxy, or C ３ to C ５ cycloalkyl, and R １０ each independently represents -H or C １ to C ３ alkyl], or a pharmaceutically acceptable salt thereof.

2. Formula: [Chemical Formula 3] The compound according to claim 1, or a pharmaceutically acceptable salt thereof, having

3. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R is -H.

4. R １ is given by the formula: 【Chemical Formula 4】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof, which is a group of

5. R １ is the formula 【Chemical Formula 5】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof, which is a group of

6. R ９ is, independently of each other, -H, halogen, C １ ~C ６ alkyl, C １ ~C ６ haloalkyl, C １ ~C ６ alkoxy, or C ３ ~C ５ cycloalkyl, the compound according to claim 1, or a pharmaceutically acceptable salt thereof.

7. R ９ is, independently of each other, -H, halogen, C １ ~C ３ alkyl, or C １ ~C ３ haloalkyl, the compound according to claim 1, or a pharmaceutically acceptable salt thereof.

8. R １ is the formula 【Chemical Formula 6】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof, which is a group of

9. R ２ is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, benzo[d]oxazol - 2(3H) - one, 1,3 - dihydro - 2H - pyrrolo[2,3 - b]pyridin - 2 - one, or 2,3 - dihydro - [1,4]dioxino[2,3 - b]pyridine, or an optionally substituted bicyclic heteroaryl selected from indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, quinazoline, or naphthyridine, wherein the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from halogen and C １ to C ６ alkyl, and the optionally substituted bicyclic heteroaryl is -CN, halogen, C １ to C ６ haloalkyl, C １ to C ６ alkoxy, C １ to C ６ haloalkoxy, -SO ２ R １０ , -CONR １０ R １０ , -NR １０ R １０ , -NR １０ CO ２ R １０ , optionally substituted C １ to C ６ alkyl, optionally substituted C ２ to C ６ alkenyl, optionally substituted C ２ to C ６ alkynyl, optionally substituted C ３ to C ５ Optionally substituted heterocycles independently selected from cycloalkyl, pyrrolidine, pyrrolidinone, piperidine, or morpholine, optionally substituted phenyl, optionally substituted 1,3-benzodioxole, optionally substituted 2,3-dihydro-1,4-benzodioxin, or optionally substituted heteroaryls selected from pyridine, pyrimidine, pyridazine, pyrazine, pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, optionally substituted with 1 to 3 substituents each independently selected from, said optionally substituted C １ ~C ６ alkyl, said optionally substituted C ２ ~C ６ alkenyl, or said optionally substituted C ２ ~C ６ alkynyl, each of which is optionally substituted with -CN, -OH, oxetanyl, or C １ ~C ３ alkoxy, said optionally substituted C ３ ~C ５ cycloalkyl, said optionally substituted phenyl, said optionally substituted 1,3-benzodioxole, said optionally substituted 2,3-dihydro-1,4-benzodioxin, said optionally substituted heterocycle, or said optionally substituted heteroaryl, each of which is optionally substituted with 1 to 3 substituents each independently selected from halogen, C １ ~C ３ alkyl, C １ ~C ３ haloalkyl, C １ ~C ３ alkoxy, C １ ~C ３ haloalkoxy, -SO ２ R １０ -, -NR １０ R １０ -, -OH, or -CN, the compound according to claim 1, or a pharmaceutically acceptable salt thereof.

10. R ２ is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, benzod[d]oxazol - 2(3H) - one, 1,3 - dihydro - 2H - pyrrolo[2,3 - b]pyridin - 2 - one, or 2,3 - dihydro - [1,4]dioxino[2,3 - b]pyridine, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolopyridine, furopyridine, pyrazolopyridine, imidazopyridine, pyrazolopyrimidine, imidazopyridazine, phthalazine, triazolopyridine, benzimidazole, pyrrolopyrimidine, thiazolopyridine, benzotriazole, benzoxazole, benzothiazole, pyrrolopyrazine, quinazoline, or naphthyridine, wherein the optionally substituted bicyclic ring is optionally substituted with 1 - 3 substituents independently selected from halogen and C １ ~C ６ alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 - 3 substituents independently selected from - CN, halogen, C １ ~C ６ haloalkyl, C １ ~C ６ alkoxy, - OH or oxetanyl - substituted C １ ~C ６ alkyl, or is optionally substituted with 1 - 3 substituents independently selected from heteroaryl selected from pyridine or oxazole, the compound according to claim 1, or a pharmaceutically acceptable salt thereof.

11. R ２ is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, indolin - 2 - one, benzo[d]oxazol - 2(3H) - one, 1,3 - dihydro - 2H - pyrrolo[2,3 - b]pyridin - 2 - one, or 2,3 - dihydro - [1,4]dioxino[2,3 - b]pyridine, or an optionally substituted bicyclic heteroaryl selected from indole, indazole, pyrrolo[2,3 - b]pyridine, pyrrolo[3,2 - b]pyridine, furo[2,3 - c]pyridine, furo[3,2 - c]pyridine, pyrazolo[1,5 - a]pyridine, pyrazolo[3,4 - b]pyridine, pyrazolo[3,4 - c]pyridine, pyrazolo[4,3 - b]pyridine, imidazo[1,2 - a]pyridine, imidazo[1,5 - a]pyridine, pyrazolo[1,5 - a]pyrimidine, imidazo[1,2 - b]pyridazine, phthalazine, [1,2,4]triazolo[4,3 - a]pyridine, triazolo[1,5 - a]pyridine, benzimidazole, pyrrolo[2,3 - d]pyrimidine, thiazolo[5,4 - b]pyridine, benzotriazole, 1,3 - benzoxazole, 1,3 - benzothiazole, pyrrolo[1,2 - a]pyrazine, quinazoline, or 1,7 - naphthyridine, wherein the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents independently selected from halogen and C １ ~C ６ alkyl, and the optionally substituted bicyclic heteroaryl is optionally substituted with 1 to 3 substituents independently selected from -CN, halogen, C １ ~C ６ haloalkyl, C １ ~C ６ alkoxy, -OH or oxetanyl - substituted C １ ~C ６ alkyl, or is optionally substituted with 1 to 3 substituents independently selected from heteroaryl selected from pyridine or oxazole, the compound according to claim 1, or a pharmaceutically acceptable salt thereof.

12. R ２ is given by the formula: 【Chemical Formula 7】 【Chemical Formula 8】 【Chemical Formula 9】 【Chemical Formula 10】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof, which is a group of

13. R ２ is the formula: 【Chemical 11】 【Chemical 12】 【Chemical 13】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof, which is a group of

14. R ３ is -H, -CN, C １ ~C ３ alkyl, or C １ ~C ３ haloalkyl, the compound according to claim 1, or a pharmaceutically acceptable salt thereof.

15. R ３ The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R is -H or methyl.

16. R ４ The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R is -H.

17. R ５ is -H, halogen, C １ ~C ３ alkyl, or C １ ~C ３ haloalkyl, the compound according to claim 1, or a pharmaceutically acceptable salt thereof.

18. R ６ The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R is -H or halogen.

19. R ７ The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R is methyl.

20. R ８ The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R is -H.

21. 【Fig. 14】 【Chemical Formula 15】 【Chemical 16】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof, selected from the group consisting of

22. 【Fig. 17】 【Chemical 18】 【Chemical Formula 19】 【Chemical 20】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof, selected from the group consisting of

23. 【Fig. 21】 【Chemical 22】 【Chemical 23】 【Chemical 24】 【Chemical 25】 【Chemical 26】 【Chemical 27】 【Chemical Formula 28】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof, selected from the group consisting of

24. 【Fig. 29】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof, selected from the group consisting of

25. 【Fig. 30】 【Chemical 31】 【Chemical 32】 【Chemical 33】 【Chemical 34】 【Chemical 35】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof, selected from the group consisting of

26. A pharmaceutical composition comprising the compound according to any one of claims 1 to 25, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

27. A medicament for treating a disease or disorder related to the regulation of phosphoinositide 3-kinase (PI3K), comprising the compound according to any one of claims 1 to 25, or a pharmaceutically acceptable salt thereof.

28. The medicament according to claim 27, wherein the PI3K is PI3Kα.

29. The medicament according to claim 27, wherein the PI3K related to the disease or disorder has an H1047R mutation.

30. The medicament according to claim 27, wherein the disease or disorder is cancer.

31. The medicament according to claim 30, 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.

32. The medicament according to claim 30, wherein the cancer is breast cancer.

33. The medicament according to claim 30, wherein the cancer is a progressive or metastatic breast cancer that is hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-).

34. The medicament according to claim 27, wherein the disease or disorder is CLOVES syndrome (Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Scoliosis / Skeletal and Spinal Syndrome) or PIK3CA-related overgrowth spectrum disorder (PROS).

35. A medicament for inhibiting phosphoinositide 3-kinase (PI3K), comprising the compound according to any one of claims 1 to 25 or a pharmaceutically acceptable salt thereof.

36. A medicament for treating cancer or a disorder, comprising the compound according to any one of claims 1 to 25 or a pharmaceutically acceptable salt thereof.

37. The medicament according to claim 36, 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.

38. The medicament according to claim 36, wherein the cancer is breast cancer.

39. The medicament according to claim 36, wherein the cancer is a progressive or metastatic breast cancer that is hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-).

40. The medicament according to claim 36, wherein the disorder is CLOVES syndrome (Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Scoliosis / Skeletal and Spinal Syndrome) or PIK3CA-related overgrowth spectrum disorder (PROS).

41. Use of the compound according to any one of claims 1 to 25 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating a disease related to the regulation of PI3K.

42. The use according to claim 41, wherein the disease related to the regulation of PI3K is cancer.

43. The use according to claim 42, 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.

44. The use according to claim 42, wherein the cancer is breast cancer.

45. The use according to claim 42, wherein the cancer is a progressive or metastatic breast cancer that is hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-).

46. The use according to claim 41, wherein the disease is CLOVES syndrome (Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevus, Scoliosis / Skeletal and Spinal Syndrome) or PIK3CA-related overgrowth syndrome (PROS).

47. Formula: 【Chemical 36】 [wherein, R １ is the formula: 【Chemical 37】 is a group of, R ２ is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxin, isoindolin - 1 - one, indolin - 2 - one, or benzod[d]oxazol - 2(3H) - one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is condensed with a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), and the optionally substituted bicyclic ring is １ optionally substituted with 1 to 3 substituents each independently selected from C ６ -C alkyl, and the optionally substituted bicyclic heteroaryl is -CN, halogen, C １ -C ６ haloalkyl, C １ -C ６ alkoxy, C １ -C ６ haloalkoxy, optionally substituted C １ -C ６ alkyl, optionally substituted C ３ -C ５ cycloalkyl, an optionally substituted heterocyclic ring selected from pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, each independently selected from 1 to 3 substituents, and the optionally substituted C １ -C ６ alkyl is optionally substituted with -CN, -OH, or C １ -C ３ alkoxy, and the optionally substituted C ３ -C ５ cycloalkyl, the optionally substituted phenyl, the optionally substituted heterocyclic ring, or the optionally substituted heteroaryl is each halogen, C １ ~C ３ alkyl, C １ ~C ３ haloalkyl, C １ ~C ３ alkoxy, C １ ~C ３ haloalkoxy, -NR １０ R １０ is optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, R ３ is -H, -CN, C １ ~C ３ alkyl, or C １ ~C ３ haloalkyl, and R ４ is -H or halogen, R ５ is -H, halogen, C １ ~C ３ alkyl, or C １ ~C ３ haloalkyl, and R ６ is -H or halogen, R ７ is -CN, methyl, or trifluoromethyl, and R is -H, R ９ each independently represents -H, halogen, methyl, C １ to C ３ haloalkyl, or cyclopropyl, R １０ each independently represents -H or C １ ~C ３ alkyl], or a pharmaceutically acceptable salt thereof.

48. Formula: 【Chemical Formula 38】 [wherein, R is -H or C １ ~C ３ is alkyl, R １ is the formula: 【Chemical 39】 is a group of, R ２ is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxin, isoindolin - 1 - one, or benzod[d]oxazol - 2(3H) - one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), and the optionally substituted bicyclic ring is optionally substituted with 1 to 3 substituents each independently selected from C １ to C ６ alkyl, and the optionally substituted bicyclic heteroaryl is selected from - CN, halogen, C １ to C ６ haloalkyl, C １ to C ６ alkoxy, C １ to C ６ haloalkoxy, - SO ２ R １０ -, - CONR １０ R １０ -, - NR １０ R １０ -, - NR １０ CO ２ R １０ an optionally substituted C １ to C ６ alkyl, an optionally substituted C ３ to C ５ cycloalkyl, an optionally substituted heterocyclic ring selected from pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, and is optionally substituted with 1 to 3 substituents each independently selected from the above, and the optionally substituted C １ to C ６ alkyl is - CN, - OH, or C １ to C ３ Optionally substituted with alkoxy, the optionally substituted C ３ -C ５ cycloalkyl, the optionally substituted phenyl, the optionally substituted heterocycle, or the optionally substituted heteroaryl is each halogen, C １ -C ３ alkyl, C １ -C ３ haloalkyl, C １ -C ３ alkoxy, C １ -C ３ haloalkoxy, -NR １０ R １０ is optionally substituted with 1 to 3 substituents independently selected from each of -OH, or -CN, R ３ is -H, -CN, C １ ~C ６ alkyl, or C １ ~C ６ haloalkyl, and R ４ 、R ５ 、and R ６ are each independently -H, halogen, C １ to C ６ alkyl, or C １ to C ６ haloalkyl, and R ７ is -CN, C １ ~C ６ alkyl, or C １ ~C ６ haloalkyl, and R ８ is -H or C １ ~C ６ alkyl, and R ９ each independently represents -H, halogen, C １ to C ６ alkyl, C １ to C ６ haloalkyl, C １ to C ６ alkoxy, or C ３ to C ５ cycloalkyl, and R １０ each independently represents -H or C １ to C ３ alkyl], or a pharmaceutically acceptable salt thereof.

49. Formula: 【Chemical 40】 The compound according to claim 48, or a pharmaceutically acceptable salt thereof, having

50. R １ is the formula: 【Chemical Formula 41】 is a group of R ２ is an optionally substituted bicyclic ring selected from 1,3 - benzodioxole, 2,3 - dihydro - 1,4 - benzodioxine, isoindolin - 1 - one, or benzod[d]oxazol - 2(3H) - one, or an optionally substituted bicyclic heteroaryl (wherein a phenyl, pyridine, pyrazine, pyrimidine, or pyridazine ring is fused to a pyrrole, furan, thiophene, pyrazole, isoxazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrazine, pyrimidine, or pyridazine ring), and the optionally substituted bicyclic ring is １ optionally substituted with 1 to 3 substituents each independently selected from C ６ to C １ alkyl, and the optionally substituted bicyclic heteroaryl is - CN, halogen, C ６ to C １ haloalkyl, C ６ to C １ alkoxy, C ６ to C １ haloalkoxy, optionally substituted C ６ to C ３ alkyl, optionally substituted C ５ to C １ cycloalkyl, an optionally substituted heterocyclic ring selected from pyrrolidine, pyrrolidinone, piperidine, or morpholine, an optionally substituted phenyl, or an optionally substituted heteroaryl selected from pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole, each optionally substituted with 1 to 3 substituents each independently selected therefrom, and the optionally substituted C ６ to C １ alkyl is optionally substituted with - CN, - OH, or C ３ to C ３ alkoxy, and the optionally substituted C ５ to C １ cycloalkyl, the optionally substituted phenyl, the optionally substituted heterocyclic ring, or the optionally substituted heteroaryl is each halogen, C to C ３ alkyl, C １ ~C ３ haloalkyl, C １ ~C ３ alkoxy, C １ ~C ３ haloalkoxy, -NR １０ R １０ is optionally substituted with 1 to 3 substituents each independently selected from -OH, or -CN, R ３ is -H, -CN, or C １ ~C ３ alkyl, and R ４ and R are each -H, R ５ is -H, halogen, C １ ~C ３ alkyl, or C １ ~C ３ haloalkyl, and R ６ is -H or halogen, R ７ is -CN, methyl, or trifluoromethyl, and R ９ is, independently of each other, -H, halogen, methyl, or C １ to C ３ haloalkyl, and R １０ is, independently of one another, -H or C １ ~C ３ alkyl, the compound according to claim 49, or a pharmaceutically acceptable salt thereof.

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