Cyclopropyl Compounds

Abstract

The present invention relates to novel heterocyclic compounds having the general formula (I') or a solvate or a pharma- ceutically acceptable salt thereof, 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 wherein R is as defined herein, compositions comprising the compounds, methods of making the compounds, and methods of using the compounds are provided. TIFF2025502712000255.tif24161

Description

[Technical Field]

[0001] The present invention relates to novel pyridine compounds useful as Kv7.2 enhancers (or positive modulators), their preparation, pharmaceutical compositions containing the compounds, kits, and their use as medicaments for the therapeutic and / or prophylactic treatment of Kv7.2-associated disorders, diseases, or disabilities, which may be selected from behavioral disorders, mood disorders, neurodevelopmental disorders, intellectual disabilities, epilepsy, neurodegenerative diseases, pain, migraine, and tinnitus. [Background technology]

[0002] Potassium channel family 7, or Q, in humans includes five proteins encoded by the genes KCNQ1, KCNQ2, KCNQ3, KCNQ4, and KCNQ5. KCNQ proteins form homotetrameric and heterotetrameric channels that respond to changes in membrane voltage and open to allow potassium ions to efflux from the cell membrane. Homomeric Kv7.2 and heteromeric Kv7.2 and Kv7.3 channels have been investigated for their unique distribution and potential role as primary regulators of neuronal excitability in many CNS and PNS pathways (Wang et al., 1998). KCNQ2 channels control neuronal resting membrane potential, spike frequency adaptation of neuronal firing, and presynaptic release. Impairment of their function, even when lost exclusively in inhibitory neurons, leads to network instability (Soh et al., 2018).

[0003] A significant proportion of childhood epilepsy is associated with KCNQ2 mutations (Lee et al., 2019). Human genetic studies have identified de novo mutations in KCNQ2 as the third most robust association with epileptic encephalopathy (EE) (Zhao et al., 2020). Whether primary or secondary EE, seizure activity worsens clinical outcomes and alters normal neurodevelopment (von Deimling, Helbig, & Marsh, 2017).

[0004] Pediatric epilepsy affects approximately 1 in 200 children (Waaler et al., 2000) and causes cognitive, behavioral, and neurological disorders (Simkin and Kiskinis, 2018). In the case of certain pathogenic KCNQ2 mutations, developmental delays are experienced by the majority of patients, although most individuals eventually become seizure-free (Kato et al., 2013). Targeting Kv7 channels provides a genetically validated target for epilepsy with a distinct mode of action among antiepileptic drugs (Gunthorpe, Large, and Sankar, 2012). Kv7.2 enhancers show potential for transforming neurodevelopmental trajectories by addressing neural network instability responsible for EE (Kessi et al., 2020).

[0005] The association between epilepsy and autism is robust (Srivastava and Sahin, 2017) and stems from a convergent phenotype driven by multiple small genetic triggers in combination with environmental factors. KCNQ2 is one of the top five ion channels associated with autism spectrum disorder (ASD) and one of the top 30 all known de novo mutations in ASD (Zhao et al., 2020).

[0006] Another defining feature of ASD, atypical sensory processing (ASP) (Thye et al., 2018), is also driven by convergent genetics seen in twin comparison studies (Neufeld et al., 2021). The biology responsible for increased sensory sensitivity has been studied in preclinical models, where multisensory hyperexcitability emerges despite genetic manipulations that initially drive pathological neurodevelopment. Some genes whose manipulations result in sensory sensitivity include CNTNAP2 (Penagarikano et al., 2011), SHANK3 (Holder and Quach, 2016), and GABRB3 (Tanaka et al., 2012). Kv7.2 enhancers show potential for modifying neurodevelopmental trajectories in ASD by normalizing network stability, neural information processing, and sensory abnormalities, which ultimately contribute to atypical social and repetitive behaviors in ASD. Interestingly, KCNQ2 knockout mice exhibit repetitive behaviors as well as abnormal exploratory and social behaviors (Kim et al., 2019).

[0007] Kv7.2 enhancers have also shown promise in syndromic neurodevelopmental disorders, in part due to the prevalence and impact of epilepsy ( Budisteanu et al., 2020 ). For example, epilepsy is common in Angelman syndrome (>80%), with most cases beginning before the age of 3 years ( Fiumara et al., 2010 ).

[0008] Another neurodevelopmental disorder, Dup15q syndrome (Dup15q), is caused by a partial duplication of chromosome 15, which confers a significant risk for autism spectrum disorder, epilepsy, and intellectual disability. Induced pluripotent cells derived from Dup15q patients exhibit KCNQ2 abnormalities, and the pan-Kv7 channel opener retigabine partially corrects their phenotype (Fink et al., 2018). Epilepsy is central to Dup15q, and Kv7.2 enhancers offer potential for reversing this neurodevelopmental disorder.

[0009] In fragile X syndrome, approximately 15% of individuals experience epilepsy (Berry-Kravis, 2002) along with abnormal sensory processing (McCullagh et al., 2020). KCNQ2 (Kv7.2 gene) is downregulated in the absence of fragile X mental retardation protein (FMRP) in rodent models (Zhang et al., 2018). Therefore, Kv7.2 enhancers may positively influence fragile X by acting on both epilepsy and sensory processing.

[0010] Infantile epilepsy is associated with intellectual disability, and KCNQ2 de novo mutations are significantly associated with intellectual disability (Zhao et al., 2020). Kv7.2 augmentation may address the underlying biology that exacerbates disability.

[0011] For all these neurodevelopmental disorders, early diagnosis and identification of the correct antiepileptic treatment are at the core of strategies aimed at normalizing the neurodevelopmental trajectory.

[0012] Among behavioral disorders, Kv7.2 enhancers have shown promise in attention-deficit hyperactivity disorder (ADHD) and major depressive disorder (MDD, depression). Some patients with KCNQ2 mutations and mild epilepsy phenotypes exhibit cognitive delays and ADHD (Lee et al., 2019). Kv7.2 enhancers have been suggested to treat neural network instability and behavioral impulsivity associated with ADHD. In the MDD space, retigabine (a Kv7 opener) has shown antidepressant efficacy in patients by acting on the brain's reward center (Tan et al., 2018). The significant reduction in depressive symptoms observed with retigabine positions Kv7.2 enhancers as a potential treatment for MDD.

[0013] The therapeutic potential of Kv7.2 enhancers in pain sensitivity is supported by the localization of Kv7.2 channels in the dorsal root ganglion and their established role in pain perception (Brown and Passmore, 2009). Nonselective Kv7.2 enhancers have shown efficacy in reducing the excitability of human peripheral axons (Lang et al., 2008). Retigabine has already shown some efficacy in preclinical pain models (Korsgaard et al., 2005; Xu et al., 2010; Wu et al., 2017). Retigabine also demonstrates efficacy in controlling spreading depression, a wave of cellular depolarization associated with migraine (Aiba and Noebels, 2021).

[0014] Among sensory abnormalities, abnormal plasticity of KCNQ2 channels has been strongly linked to the induction of tinnitus (Li, Choi, & Tzounopoulos, 2013). This link is based on the localization of Kv7.2 channels in the cochlea (Jin et al., 2009) and how cochlear damage depends on neuronal excitability driven by Kv7.2 channel closure (Liu, Glowatzki, & Fuchs, 2015). Retigabine prevents the development of tinnitus in preclinical models (Li, Choi, & Tzounopoulos, 2013). It is intriguing to note that tinnitus and hyperacusis are more prevalent in ASD than in the general population, supporting evidence of how KCNQ2 pathology is linked across indications (Danesh et al., 2015).

[0015] In neurodegenerative diseases, K+ homeostasis dysregulation in chronic neuroinflammatory conditions is central to disease progression. For example, in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease of the motor nervous system (Hardiman et al., 2017), diverse genetics converge on motor neuron excitotoxicity (Kanai et al., 2006; Pasinelli and Brown, 2006), and specifically, axonal hyperexcitability predicts survival (Kanai et al., 2012). Patient-derived motor neurons exhibit membrane hyperexcitability, and the tool compound retigabine (a pan-Kv7 enhancer) rescues the phenotype (Wainger et al., 2014). Motor neuron hyperexcitability was discovered early in presymptomatic in vivo systems, where it triggers disease progression (Kuo et al., 2004). Recently, clinical trials in ALS using retigabine have shown efficacy against functional biomarkers of ALS ( Wainger et al., 2021 ) and preclinically protect against peripheral neuropathy ( Nodera et al., 2011 ).

[0016] In Alzheimer's disease (AD), neuronal hyperexcitability and network instability (Frere and Slutsky, 2018) are early features of both sporadic AD IPSC models (Ghatak et al., 2019) and genetic in vivo models (Palop et al., 2007; Kazim et al., 2017; Styr and Slutsky, 2018). Network instability exacerbates the proteinopathy (Dolev et al., 2013; Frere and Slutsky, 2018) and affects patients (Vossel et al., 2013; Lam et al., 2017).

[0017] Because the degeneration of motor and cortical neurons can be significantly slowed by reducing aberrant neuronal activity, enhancing Kv7.2 may be an effective way to halt such aberrant activity and alter the neurodegenerative trajectory of the disease.

[0018] Therefore, enhancing Kv7.2 activity is a promising strategy for treating or preventing Kv7.2-related diseases, including neurodevelopmental disorders such as autism and fragile X, epilepsy, intellectual disability, depression, attention deficit hyperactivity disorder, motor neuron excitability, pain, migraine, and sensory processing disorders.

[0019] WO 2020 / 163268 relates to pyridine urea derivatives as KCNQ potentiators.

[0020] U.S. Patent No. 5,384,330 relates to pharmacologically active 1,2,4-triaminobenzene derivatives that modulate the potassium ion channels Kv7.2-Kv7.5 (KCNQ2-KCNQ5) for the treatment of drug-resistant epilepsy. These compounds have shown tolerability problems and other side effects. [Prior art documents] [Patent documents]

[0021] [Patent Document 1] International Publication No. 2020 / 163268 [Patent Document 2] U.S. Patent No. 5,384,330 [Non-patent literature]

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(2015) "Tinnitus and hyperacusis in autism spectrum disorders with emphasis on high functioning individuals diagnosed with Asperger's Syndrome", International journal of pediatric otorhinolaryngology, 79(10), pp. 1683-1688. [Non-patent document 6] von Deimling, M., Helbig, I. and Marsh, ED (2017) "Epileptic Encephalopathies-Clinical Syndromes and Pathophysiological Concepts", Current neurology and neuroscience reports, 17(2), p. 10. [Non-Patent Document 7] Dolev, I. et al. (2013) "Spike bursts increase amyloid-β 40 / 42 ratio by inducing a presenilin-1 conformational change", Nature neuroscience, 16(5), pp. 587-595. [Non-patent document 8] Fink, JJ et al. (2018) “Hyperexcitable phenotypes in iPSC-derived neurons from patients with 15q11-q13 duplication syndrome, a genetic form of autism,” BioRxiv.biorxiv.org. Available at https: / / www.biorxiv.org / content / 10.1101 / 286336v1.abstract. [Non-Patent Document 9] Fiumara, A. et al. (2010) “Epilepsy in patients with Angelman syndrome”, Italian Journal of Pediatrics, p. 31. doi:10.1186 / 1824-7288-36-31. [Non-Patent Document 10] Frere, S. and Slutsky, I. (2018) "Alzheimer's Disease: From Firing Instability to Homeostasis Network Collapse", Neuron, 97(1), pp. 32-58. [Non-Patent Document 11] Ghatak, S. et al. (2019) "Mechanisms of hyperexcitability in Alzheimer's disease hiPSC-derived neurons and cerebral organoids vs isogenic controls", eLife, 8.doi:10.7554 / eLife.50333. [Non-Patent Document 12] Gunthorpe, MJ, Large, CH and Sankar, R. (2012) "The mechanism of action of retigabine(ezogabine), a first-in-class K+channel opener for the treatment of epilepsy", Epilepsia, 53(3), pp. 412-424. [Non-Patent Document 13] Hardiman, O. et al. (2017) “Amyotrophic lateral sclerosis”, Nature reviews. Disease primers, 3, p. 17071. [Non-Patent Document 14] Holder, JL, Jr and Quach, MM (2016) "The spectrum of epilepsy and electroencephalographic abnormalities due to SHANK3 loss-of-function mutations", Epilepsia, 57(10), pp. 1651-1659. [Non-Patent Document 15] Jin, Z. et al. (2009) "Expression and localization of K channels KCNQ2 and KCNQ3 in the mammalian cochlea", Audiology&neuro-otology, 14(2), pp. 98-105. [Non-Patent Document 16] Kanai, K. et al. (2006) "Altered axonal excitability properties in amyotrophic lateral sclerosis: impaired potassium channel function related to disease stage", Brain: a journal of neurology, 129(Pt4), pp. 953-962. [Non-Patent Document 17] Kanai, K. et al. (2012) "Motor axonal excitability properties are strong predictors for survival in amyotrophic lateral sclerosis", Journal of neurology, neurosurgery, and psychiatry, 83(7), pp. 734-738. [Non-Patent Document 18] Kato, M. et al. (2013) "Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation", Epilepsia, 54(7), pp. 1282-1287. [Non-Patent Document 19] Kazim, SF et al. (2017) "Early-Onset Network Hyperexcitability in Presymptomatic Alzheimer's Disease Transgenic Mice Is Suppressed by Passive Immunization with Anti-Human APP / Aβ Antibody and by mGluR5 Blockade", Frontiers in aging neuroscience, 9, p. 71. [Non-Patent Document 20] Kessi, M. et al. (2020) "Intellectual Disability and Potassium Channelopathies: A Systematic Review", Frontiers in genetics, 11, p. 614. [Non-Patent Document 21] Kim, EC et al. (2019) “Heterozygous loss of epilepsy gene KCNQ2 alters social, repetitive, and exploratory behaviors”, Genes, Brain and Behavior.doi:10.1111 / gbb.12599. [Non-Patent Document 22] Korsgaard, MPG et al. (2005) "Anxiolytic effects of Maxipost (BMS-204352) and retigabine via activation of neuronal Kv7 channels", The Journal of pharmacology and experimental therapeutics, 314(1), pp. 282-292. [Non-Patent Document 23] Kuo, JJ et al. (2004) "Hyperexcitability of cultured spinal motoneurons from presymptomatic ALS mice", Journal of neurophysiology.physiology.org, 91(1), pp. 571-575. [Non-Patent Document 24] Lam, AD et al. (2017) "Silent hippocampal seizures and spikes identified by foramen ovale electrodes in Alzheimer's disease", Nature medicine, 23(6), pp. 678-680. [Non-Patent Document 25] Lang, PM et al. (2008) "Retigabine reduces the excitability of unmyelinated peripheral human axons", Neuropharmacology, 54(8), pp. 1271-1278. [Non-Patent Document 26] Lee, I.-C. et al. (2019) "KCNQ2 mutations in childhood nonlesional epilepsy: Variable phenotypes and a novel mutation in a case series", Molecular genetics&genomic medicine, 7(7), p. e00816. [Non-Patent Document 27] Li, S., Choi, V. and Tzounopoulos, T. (2013) "Pathogenic plasticity of Kv7.2 / 3 channel activity is essential for the induction of tinnitus", Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 110(24), pp. 9980-9985. [Non-patent document 28] Liu, C., Glowatzki, E. and Fuchs, P.A. (2015) "Unmyelinated type II afferent neurons report cochlear damage", Proceedings of the National Academy of Sciences of the United States of America, 112(47), pp. 14723-14727. [Non-Patent Document 29] McCullagh, EA et al. (2020) "Mechanisms underlying auditory processing deficits in Fragile X syndrome", FASEB journal:official publication of the Federation of American Societies for Experimental Biology.doi:10.1096 / fj.201902435R. [Non-Patent Document 30] Neufeld, J. et al. (2021) "A co-twin-control study of altered sensory processing in autism", Autism: the international journal of research and practice, 25(5), pp. 1422-1432. [Non-Patent Document 31] Ng, FL et al. (2011). Expression and function of the K+channel KCNQ genes in human arteries. British Journal of Pharmacology, 162(1), 42–53. [Non-Patent Document 32] Nodera, H. et al. (2011) "Neuroprotective effects of Kv7 channel agonist, retigabine, for cisplatin-induced peripheral neuropathy", Neuroscience letters, 505(3), pp. 223-227. [Non-Patent Document 33] Palop, JJ et al. (2007) "Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease", Neuron, 55(5), pp. 697-711. [Non-Patent Document 34] Pasinelli, P. and Brown, RH (2006) "Molecular biology of amyotrophic lateral sclerosis: insights from genetics", Nature reviews. Neuroscience, 7(9), pp. 710-723. [Non-Patent Document 35] Penagarikano, O. et al. (2011) "Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits", Cell, 147(1), pp. 235-246. [Non-Patent Document 36] Simkin, D. and Kiskinis, E. (2018) "Modeling Pediatric Epilepsy Through iPSC-Based Technologies", Epilepsy currents / American Epilepsy Society, 18(4), pp. 240-245. [Non-Patent Document 37] Soh, H. et al. (2018) “Deletion of KCNQ2 / 3 potassium channels from PV+ interneurons leads to homeostatic potentiation of excitatory transmission”, eLife, 7.doi:10.7554 / eLife.38617. [Non-Patent Document 38] Srivastava, S. and Sahin, M. (2017) "Autism spectrum disorder and epileptic encephalopathy: common causes, many questions", Journal of neurodevelopmental disorders, 9, p. 23. [Non-Patent Document 39] Styr, B. and Slutsky, I. (2018) "Imbalance between firing homeostasis and synaptic plasticity drives early-phase Alzheimer's disease", Nature neuroscience, 21(4), pp. 463-473. [Non-Patent Document 40] Tan, A. et al. (2018) “Effects of the KCNQ channel opener ezogabine on functional connectivity of the ventral striatum and clinical symptoms in patients with major depressive disorder”, Molecular psychiatry.doi:10.1038 / s41380-018-0283-2. [Non-Patent Document 41] Tanaka, M. et al. (2012) "GABRB3, Epilepsy, and Neurodevelopment," in Noebels, JL et al. (eds.) Jasper's Basic Mechanisms of the Epilepsies. Bethesda (MD): National Center for Biotechnology Information (US). [Non-Patent Document 42] Thye, MD et al. (2018) "The impact of atypical sensory processing on social impairments in autism spectrum disorder", Developmental cognitive neuroscience.Elsevier, 29, pp. 151-167. [Non-Patent Document 43] Vossel, KA et al. (2013) "Seizures and epileptiform activity in the early stages of Alzheimer disease", JAMA neurology, 70(9), pp. 1158-1166. [Non-Patent Document 44] Waaler, PE et al. (2000) "Prevalence, classification, and severity of epilepsy in children in western Norway", Epilepsia, 41(7), pp. 802-810. [Non-Patent Document 45] Wainger, BJ et al. (2014) "Intrinsic membrane hyperexcitability of amyotrophic lateral sclerosis patient-derived motor neurons", Cell reports, 7(1), pp. 1-11. [Non-Patent Document 46] Wainger, BJ et al. (2021) "Effect of Ezogabine on Cortical and Spinal Motor Neuron Excitability in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial", JAMA neurology, 78(2), pp. 186-196. [Non-Patent Document 47] Wang, HS et al. (1998) "KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel", Science. American Association for the Advancement of Science, 282(5395), pp. 1890-1893. [Non-Patent Document 48] Wu, Z. et al. (2017) "Activation of KCNQ Channels Suppresses Spontaneous Activity in Dorsal Root Ganglion Neurons and Reduces Chronic Pain after Spinal Cord Injury", Journal of neurotrauma, 34(6), pp. 1260-1270. [Non-Patent Document 49] Xu, W. et al. (2010) “Activation of voltage-gated KCNQ / Kv7 channels by anticonvulsant retigabine attenuates mechanical allodynia of inflammatory temporomandibular joint in rats”, Molecular pain, 6, p. 49. [Non-Patent Document 50] Zhang, F. et al. (2018) "Fragile X mental retardation protein modulates the stability of its m6A-marked messenger RNA targets", Human molecular genetics.Oxford Academic, 27(22), pp. 3936-3950. [Non-Patent Document 51] Zhao, G. et al. (2020) "Gene4Denovo: an integrated database and analytic platform for de novo mutations in humans", Nucleic acids research. Oxford Academic, 48(D1), pp. D913-D926. Summary of the Invention [Problem to be solved by the invention]

[0023] To date, no drug acting on Kv7.2 has been approved for the treatment of any of the diseases, disorders, or disabilities described herein, and therefore, there remains a need for Kv7.2 modulators that provide therapeutic benefits.Furthermore, it would be beneficial to have a Kv7.2 modulator that is more highly selective than other Kv7 channels.For example, there is a need for Kv7.2 modulators that provide a combination of favorable pharmacological properties, such as potency, selectivity, and metabolic stability.

[0024] It is therefore an object of the present invention to provide selective Kv7.2 enhancers with favorable pharmacological properties useful as Kv7.2 enhancers (or positive modulators) for the therapeutic and / or prophylactic treatment of Kv7.2-associated disorders, diseases, or disabilities. [Means for solving the problem]

[0025] In some embodiments, a compound of formula (I') [ka] (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 is as defined herein), or a solvate or pharmaceutically acceptable salt thereof, is provided herein.

[0026] In a further aspect, the present invention provides a pharmaceutical composition comprising a compound of formula (I'), or a solvate or pharmaceutically acceptable salt thereof.

[0027] In a further aspect, the present invention provides a compound of formula (I'), or a solvate or pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising same, for use as a therapeutically active substance.

[0028] In a further aspect, the present invention provides a compound of formula (I'), or a solvate or pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same, for use in the therapeutic and / or prophylactic treatment of a disorder, disease or disability associated with Kv7.2.

[0029] In a further aspect, the present invention provides the use of a compound of formula (I'), or a solvate or pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same, in the therapeutic and / or prophylactic treatment of a disorder, disease, or disability associated with Kv7.2.

[0030] In a further aspect, the present invention provides the use of a compound of formula (I'), or a solvate or pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same, for the manufacture of a medicament for the therapeutic and / or prophylactic treatment of a disorder, disease, or disability associated with Kv7.2.

[0031] In a further aspect, the present invention provides a method for the therapeutic and / or prophylactic treatment of a disorder, disease, or disability associated with Kv7.2, comprising administering a therapeutically effective amount of a compound of formula (I'), or a solvate or pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same.

[0032] In a further aspect, the present invention provides a kit for use in the therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease, or disability, comprising: a) a compound of formula (I'), or a solvate or pharmaceutically acceptable salt thereof, or a pharmaceutical composition or pharmaceutical composition for use comprising the same; b) Instructions for use and A kit comprising:

[0033] The compounds of formula (I') described herein, or solvates or pharmaceutically acceptable salts thereof, offer a combination of favorable pharmacological properties, such as potency, selectivity, and metabolic stability.

[0034] Reasonable metabolic stability is important to ensure adequate pharmacological half-life, which is best achieved with compounds with a human hepatic microsomal clearance rate of less than 20 μL / min / mg. Selectivity within the Kv7 family is desirable to avoid effects on tissues that are not therapeutic for the indications described in this invention. For example, effects on Kv7.4 and Kv7.5 in skeletal and smooth muscle affect human arterial function, and KCNQ2 expression is minimal or undetectable in these tissues (Ng et al., 2011).

[0035] The same particular embodiment as above also relates to a compound of formula (I) [ka] (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 as defined herein), or a solvate or a pharmaceutically acceptable salt thereof, form part of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0036] definition It should be understood that any feature, integer, characteristic, compound, chemical moiety, or group described in connection with a particular aspect, embodiment, or example of the invention is applicable to any other aspect, embodiment, or example described herein, except where inconsistent therewith. All features disclosed herein (including any accompanying claims, abstract, and drawings), and / or all steps of any method or process so disclosed, may be combined in any combination, except combinations in which at least some of such features and / or steps are mutually exclusive. The invention is not limited to the details of any embodiment expressly disclosed herein. Any embodiment described in this application may be combined with any other embodiment. The invention extends to any novel or any novel combination of features disclosed herein (including any accompanying claims, and abstract), or any novel or any novel combination of any embodiment or step of any method or process so disclosed.

[0037] All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety.

[0038] The nomenclature used in this application is based on IUPAC systematic nomenclature unless otherwise indicated.

[0039] Any open valency appearing on a carbon, oxygen, sulfur, or nitrogen atom in the structures herein indicates the presence of a hydrogen, unless otherwise indicated.

[0040] When used in the therapeutic and / or prophylactic treatment of a disorder, disease, or disability described herein, "administer," "administered," or "administering" means providing a compound of the invention to a patient or subject by any method, such as infusion, inhalation, injection, paste, suppository, or tablet.

[0041] As used herein, the terms "including," "containing," and "comprising" are used in an open, non-limiting sense.

[0042] As used in this disclosure, the articles "a" and "an" may refer to one or to more than one (e.g., to at least one) of the grammatical object of the article. For example, "an element" may mean one element or more than one element.

[0043] The term "substituent" refers to an atom or group of atoms that replaces a hydrogen atom of a parent molecule.

[0044] As described herein, chemical groups within the present disclosure can be "unsubstituted" or "substituted" with one or more substituents (e.g., 1, 2, 3, 4, or 5), such as those generally described herein or as exemplified by particular classes, subclasses, and species of the present disclosure. Generally, the term "substituted" refers to the replacement of a hydrogen atom in a given structure with a specified substituent. In some embodiments, two or more hydrogen atoms are replaced with a specified substituent (e.g., two hydrogen atoms are replaced with one oxo substituent). Combinations of substituents contemplated by the present disclosure are typically those that result in the formation of stable or chemically viable compounds. In one embodiment, an optionally substituted group has one substituent. In another embodiment, an optionally substituted group has two substituents. In another embodiment, an optionally substituted group has three substituents. In another embodiment, an optionally substituted group has a substituent as described herein. As used herein, the term "unsubstituted" may mean that the specified group has no substituents beyond the recited moieties (e.g., where a valence is satisfied by hydrogen).

[0045] The term "effective amount" or "therapeutically effective amount" refers to an amount of a compound of formula (I') or (I), or a solvate or pharmaceutically acceptable salt thereof, or a pharmaceutical composition sufficient to produce a desired therapeutic outcome, such as reducing the duration and severity of, stabilizing the severity of, or eliminating one or more signs, symptoms, or causes of, a disease, disorder, or disability. With respect to therapeutic use, beneficial or desired results can include, for example, reducing one or more (biochemical, histological, and / or behavioral) symptoms caused by a disease, disorder, or disability, including its complications and intermediate pathological phenotypes that appear during the progression of the disease, disorder, or disability; increasing the quality of life of a subject suffering from a disease, disorder, or disability; reducing the dosage of other medications required to treat the disease, disorder, or disability; enhancing the effectiveness of other medications; delaying the progression of the disease, disorder, or disability; and / or prolonging patient survival.

[0046] The term "pharmaceutically acceptable salt" refers to a salt that retains the biological effectiveness and properties of the free base or free acid, and is not biologically or otherwise undesirable. Salts are formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like, especially hydrochloric acid, as well as organic acids, such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, N-acetylcysteine, and the like. In addition, these salts can be prepared by adding an inorganic or organic base to the free acid. Salts derived from inorganic bases include, but are not limited to, sodium salts, potassium salts, lithium salts, ammonium salts, calcium salts, magnesium salts, and the like.

[0047] Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, lysine, arginine, N-ethylpiperidine, piperidine, polyimine resins, and the like.

[0048] As used herein, the term "excipient" or "pharmaceutical excipient" refers to any pharmaceutically acceptable excipient that can be used in the manufacture of a drug or pharmaceutical composition, such as a tablet, containing a compound described herein (or a tautomer or pharmaceutically acceptable salt) as an active ingredient. A variety of substances can be encompassed by the term excipient, including, but not limited to, diluents, fillers, extenders, binders, disintegrants, glidants, wetting agents, coatings, emulsifiers or dispersing agents, compression / encapsulation aids, creams or lotions, lubricants, solutions for parenteral administration, materials for chewable tablets, sweeteners or flavoring agents, suspending / gelling agents, or any substance used as a wet granulator. Disintegrants refer to excipients that swell and dissolve when wetted, causing the tablet to break down in the body and release the active ingredient for absorption. Examples include cross-linked polymers such as crospovidone, croscarmellose sodium, and modified starches such as sodium starch glycolate. Fillers are excipients that increase the bulk volume and thereby fill the tablet size. Fillers allow the final product to have a volume appropriate for patient handling. Examples of fillers include plant cellulose, lactose, starch, mannitol, etc. Specific examples include lactose monohydrate (e.g., Pharmatose 200M), microcrystalline cellulose (MCC) (e.g., Avicel PH101 or Avicel PH102), and spray-dried lactose (e.g., Fast Flo 316®). Binders are excipients that hold the ingredients in a tablet together. Binders ensure that tablets and granules can be formed with the necessary mechanical strength. Examples of binders include polyvinylpyrrolidone (PV), hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), cellulose, sugar alcohols (e.g., sorbitol), proteins (e.g., gelatin), and polymers (e.g., PVP, e.g., copovidone (PVP / VA 64), PEG, etc. Lubricants are excipients that prevent ingredients from clumping together and sticking to tablet punches or capsule-filling machines. Lubricants also ensure that tablet formation and ejection can occur with low friction between the active ingredients and the wall.Examples of lubricants include minerals such as talc or silica, and fats such as stearin and magnesium stearate. Coatings may include, for example, cellulose acetate phthalate, ethylcellulose, gellan gum, maltodextrin, enteric coatings, and the like. Compression / encapsulation aids include, for example, calcium carbonate, dextrose, fructose dc (dc—"directly compressible"), honey dc, lactose (anhydrous or monohydrate; optionally combined with aspartame, cellulose, or microcrystalline cellulose), starch dc, sucrose, and the like. Creams or lotions include, for example, maltodextrin, carrageenan, and the like. Chewable tablet materials include, for example, dextrose, fructose dc, lactose (monohydrate, optionally combined with aspartame or cellulose), and the like. Suspending / gelling agents include, for example, carrageenan, sodium starch glycolate, xanthan gum, and the like. Sweeteners include, for example, aspartame, dextrose, fructose dc, sorbitol, sucrose dc, etc. Wet granulating agents include, for example, calcium carbonate, maltodextrin, microcrystalline cellulose, etc. In some cases, the term "excipient" encompasses a pharmaceutically acceptable carrier. Those skilled in the art are aware of the appropriate pharmaceutical compositions to be used in the treatment of patients and methods for their manufacture.

[0049] The term "patient" or "subject" can encompass both mammals and non-mammals. Examples of mammals can include, but are not limited to, any member of the class Mammalia: non-human primates such as humans, chimpanzees, monkeys, baboons, or rhesus monkeys, as well as other ape and monkey species; livestock animals such as cows, horses, sheep, goats, and pigs; companion animals such as rabbits, dogs, and cats; laboratory animals including rodents such as rats, mice, and guinea pigs; and the like. Examples of non-mammals include, but are not limited to, birds, fish, and the like. A "patient" or "subject" can include both humans and animals. In some preferred embodiments, the "patient" or "subject" is a human.

[0050] As used herein, the term "treat" or "treatment" is meant to refer to postponing the onset of one or more diseases, disorders, or disabilities, preventing the onset of one or more diseases, disorders, or disabilities, and / or reducing the severity of one or more symptoms of a disease, disorder, or disability that will or is predicted to develop. Thus, these terms can include alleviating one or more existing symptoms of a disease, disorder, or disability, preventing one or more additional symptoms, alleviating or preventing the underlying cause of one or more symptoms, inhibiting a disease, disorder, or disability, for example, arresting the progression of a disease, disorder, or disability, reducing a disease, disorder, or disability, inducing regression of a disease, disorder, or disability, alleviating symptoms caused by a disease, disorder, or disability, or arresting or alleviating symptoms of a disease, disorder, or disability.

[0051] The compounds of the present disclosure may exist as solvates. The term "solvate" may refer to a complex of variable stoichiometry formed by a solute and a solvent. For the purposes of this disclosure, such a solvent may not interfere with the biological activity of the solute. Examples of suitable solvents include, but are not limited to, water, MeOH, EtOH, and AcOH. Solvates in which water is the solvent molecule are typically called hydrates. Hydrates may include compositions containing stoichiometric amounts of water and compositions containing variable amounts of water. In some embodiments, solvates are excluded.

[0052] As used herein, the term "prophylaxis" includes preventing or delaying the appearance of clinical symptoms of a disease, disorder or disability that develops in patients or subjects, particularly humans, who are suffering from or susceptible to a disease, disorder or disability described herein but who have not yet experienced or exhibited clinical or subclinical symptoms of the disease, disorder or disability.

[0053] As used herein, the term "about" when referring to a value is meant to encompass variations from the specified amount, for example, in some embodiments ±20%, in some embodiments ±10%, in some embodiments ±5%, in some embodiments ±1%, in some embodiments ±0.5%, and in some embodiments ±0.1%, such variations are appropriate for practicing the disclosed methods or using the disclosed compositions.

[0054] Where a range of values ​​is provided, unless the context clearly dictates otherwise, it is understood that each intervening value, to the tenth of the unit of the lower limit, between the upper and lower limits of the range, and any other stated or intervening value in that stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges, which may be independently included in smaller ranges, are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.

[0055] As used herein, numerical ranges may include consecutive integers. For example, a range expressed as "0 to 5" includes 0, 1, 2, 3, 4, and 5.

[0056] A "metabolite" is a product produced by metabolism in the body of the specified compound or its salt. Metabolites of a compound can be identified using routine techniques known in the art, and their activity can be determined using tests such as those described herein. Such products can result from, for example, oxidation, reduction, hydrolysis, amidation, deamidation, esterification, deesterification, enzymatic cleavage, and the like, of the administered compound. Accordingly, the present invention includes metabolites of compounds of the invention, including compounds produced by a process comprising contacting a compound of this invention with a mammal for a period of time sufficient to yield a metabolic product thereof.

[0057] The term "package insert" is used to refer to instructions customarily included in commercial packaging of therapeutic products that contain information about the indications, uses, dosage, administration, contraindications, and / or warnings regarding the use of such therapeutic product.

[0058] The terms "compound of this invention" and "compounds of the present invention", "compounds of the invention", "compounds of formula (I')" and "compound of formula (I)" include compounds of formula (I'), compounds of formula (I), compounds selected from any of formulas (I*), (II**), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), etc., compounds of Table 1, 2, etc., stereoisomers, geometric isomers, solvates, pharmaceutically acceptable salts, tautomers, metabolites, prodrugs, polymorphs, and mixtures thereof.

[0059] The symbol "*" at the end of a bond or the symbol "---" drawn through a bond each refers to the point of attachment of a functional group or other chemical moiety to the remainder of the molecule of which it is a part. Thus, for example, [ka] means the substituent is attached to the remainder of the molecule as shown. [ka]

[0060] A bond drawn into a ring system (as opposed to being attached at a separate vertex) indicates that the bond may be attached to any of the suitable ring atoms.

[0061] As used herein, the term "optional" or "optionally" means that the subsequently described event or circumstance may occur, but need not necessarily occur, and that the description includes instances where the event or circumstance occurs and instances where it does not occur. For example, "optionally substituted" means that the optionally substituted moiety may incorporate a hydrogen atom or a substituent. "Optionally substituted" means that the compound may be unsubstituted or substituted as defined herein. The term "optionally substituted" means that the specified group is unsubstituted or substituted with one or more substituents independently selected from a group of possible substituents. When referring to the number of substituents, the term "one or more" means a range from one substituent to the highest possible number of substitutions, i.e., replacement of one hydrogen with a substituent to replacement of all hydrogens.

[0062] The term "independently" is used herein to indicate that a variable applies in any instance regardless of the presence or absence of variables with the same or different definitions within the same compound. Thus, in a compound where R" appears twice and is defined as "independently carbon or nitrogen," both R" can be carbon, or both R" can be nitrogen, or one R" can be carbon and the other nitrogen. In addition, for example, R 2 and R 3 is hydrogen and hydroxy C 1~6 In compounds independently selected from alkyl, R 2 and R 3 can both be hydrogen or both are hydroxy C 1~6 can be alkyl, or R 2 and R 3 One of them is hydrogen and the other is hydroxy C 1~6 It can be alkyl.

[0063] In this application, the units ul, uMol, C etc. mean μl, μMol, °C etc.

[0064] In this application,50 The term "EC" is defined as one in which the agonist effect of a compound can be determined by testing the compound in the in vitro assay described herein, in which the effect of the compound is measured over a range of compound concentrations. The resulting data is typically plotted as a concentration-response curve that follows a sigmoid function, with the concentration of the compound plotted on the x-axis and the response (agonist effect) plotted on the y-axis. 50 The term "half-maximal effective concentration" refers to the maximum response (E) observed for a compound in a given in vitro assay. max ) represents the concentration of a particular compound required to obtain 50% of the

[0065] The compounds of the present invention can exist in one or more stereoisomeric forms (e.g., they contain one or more asymmetric carbon atoms). The individual stereoisomers (enantiomers and diastereomers) and mixtures thereof are included within the scope of the subject matter disclosed herein.

[0066] Similarly, a compound or salt may exist in a tautomeric form other than that shown in its formula, and it is understood that these are also included within the scope of the subject matter disclosed herein. It is understood that the subject matter disclosed herein includes combinations and subsets of the specific groups described herein. The scope of the subject matter disclosed herein includes mixtures of stereoisomers as well as purified enantiomers or enantiomerically / diastereomerically enriched mixtures. It is understood that the subject matter disclosed herein includes combinations and subsets of the specific groups defined herein.

[0067] The compounds of the present invention may contain several asymmetric centers and may exist in the form of optically pure enantiomers, mixtures of enantiomers, e.g. racemates, optically pure diastereoisomers, mixtures of diastereoisomers, racemates of diastereoisomers or racemic mixtures of diastereoisomers.

[0068] According to the Cahn-Ingold-Prelog rules, the asymmetric carbon atom can be of the "R" or "S" configuration.

[0069] The term "chiral" refers to molecules that have the property of not being superimposable on their mirror image partners, while the term "achiral" refers to molecules that are superimposable on their mirror image partners. Chiral separation of a racemate and its enantiomeric components can be performed to separate eutomers and distomers.

[0070] The term "stereoisomers" refers to compounds which have identical chemical constitution, but differ with regard to the arrangement of the atoms or groups in space.

[0071] "Diastereomer" refers to a stereoisomer with two or more centers of chirality and whose molecules are not mirror images of one another. Diastereomers have different physical properties, such as melting points, boiling points, spectral properties, and reactivities. Mixtures of diastereomers can separate under high-resolution analytical procedures such as chromatography.

[0072] "Enantiomers" refer to two stereoisomers of a compound which are non-superimposable mirror images of one another.

[0073] Stereochemical definitions and conventions used herein generally follow those in S.P. Parker, ed., McGraw-Hill Dictionary of Chemical Terms (1984), McGraw-Hill Book Company (New York), and Eliel, E. and Wilen, S., "Stereochemistry of Organic Compounds," John Wiley & Sons, Inc. (New York, 1994). The compounds of the present invention may contain asymmetric or chiral centers and, therefore, can exist in different stereoisomeric forms. All stereoisomeric forms of the compounds of the present invention, including, but not limited to, diastereomers, enantiomers, and atropisomers, as well as mixtures thereof, e.g., racemic mixtures, are intended to form part of the present invention. Any organic compound exists in optically active form, i.e., it has the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L, or R and S, are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes d and l or (+) and (-) are used to designate the indication of rotation of plane-polarized light by a compound; (-) or l means the compound is levorotatory. Compounds with the prefix (+) or d are dextrorotatory. For a given chemical structure, these stereoisomers are identical except that they are mirror images of each other. Specific stereoisomers are also called enantiomers, and a mixture of such isomers may be called an enantiomeric mixture. A 50:50 mixture of enantiomers is called a racemic mixture or racemate, which may occur when there has been no stereoselection or stereospecificity in a chemical reaction or process.

[0074] The terms "racemic mixture" and "racemate" refer to an equimolar mixture of two enantiomeric species, devoid of optical activity.

[0075] The term "tautomer" or "tautomeric form" refers to structural isomers with different energies that are interconvertible via a low energy barrier. For example, proton tautomers (also known as prototropic tautomers) include interconversions via migration of a proton, such as keto-enol and imine-enamine isomerizations. Valence tautomers include interconversions via reorganization of some of the bonding electrons.

[0076] It should be understood that the individual enantiomers and diastereomers are included in the table below by compound name, and their corresponding structures can be readily determined therefrom. In some cases, the enantiomers or diastereomers are identified by their respective properties, such as their retention time on chiral HPLC or their biological activity (e.g., as further described in the Examples), and the absolute configuration of one or more chiral centers is arbitrarily assigned (e.g., the stereochemistry of all chiral centers is arbitrarily assigned, or the stereochemistry of one chiral center is known and the remaining chiral centers are arbitrarily assigned, etc.).

[0077] In some embodiments of the invention, only one of the possible enantiomers is used, while in other embodiments, a mixture of the possible enantiomers is used, having different percentages of each component.

[0078] In some embodiments, the compounds of the present invention are isotopically labeled by replacing one or more atoms therein with atoms having different atomic masses or mass numbers. Such isotopically labeled (e.g., radiolabeled) compounds of formula (I') or (I), or solvates or pharmaceutically acceptable salts thereof, are considered to be within the scope of the present disclosure. Examples of isotopes that can be incorporated into the compounds of the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, and iodine, for example, but not limited to, 2 H, 3 H, 11 C. 13 C. 14 C. 13 N,15 N, 15 O. 17 O. 18 O. 31 P, 32 P, 35 S, 18 F, 36 Cl, 123 I, and 125 Certain isotopically labeled compounds of the invention, for example, those incorporating a radioactive isotope, are useful in drug and / or substrate tissue distribution studies. The radioactive isotope tritium, i.e., 3 H and carbon-14, i.e., 14 C are particularly useful for this purpose given their ease of incorporation and ready means of detection. For example, compounds of the invention can be enriched with 1, 2, 5, 10, 25, 50, 75, 90, 95, or 99% of a given isotope.

[0079] In some embodiments, the compound of formula (I') or (I) or a solvate or pharmaceutically acceptable salt thereof is 2 H (deuterium), 3 H (tritium), preferably 2 It is specifically envisioned to have one or more hydrogen atoms in the structure replaced with H (deuterium). Any of the hydrogen atoms in the structure may be so replaced, but in some cases, R 2 and R 8 In particular, one or both of the hydrogen atoms present in 2 H (deuterium), 3 H (tritium), preferably 2 H (deuterium) is preferred. 2 and R 8 Both 2 H (deuterium).

[0080] 3 H, 11 C. 18 F, 15 O and 13Substitution with positron emitting isotopes, such as N, can be useful in positron emission tomography (PET) studies for examining substrate receptor occupancy. Isotopically labeled compounds of the invention can generally be prepared by conventional techniques known to those skilled in the art, or by methods analogous to those described in the Examples set forth below, substituting appropriate isotopically labeled reagents for previously employed non-isotopically labeled reagents.

[0081] In one embodiment, the present invention provides a pharmaceutically acceptable salt of a compound of the present invention, particularly a pharmaceutically acceptable salt selected from hydrochloride, fumarate, lactate (particularly derived from L-(+)-lactic acid), tartrate (particularly derived from L-(+)-tartaric acid), and trifluoroacetate. In yet a further particular embodiment, the present invention provides a compound of formula (I') or (I) as described herein, or a solvate or pharmaceutically acceptable salt thereof (i.e., as the "free base" or "free acid," respectively).

[0082] When a bond in a compound of the present invention is drawn non-stereochemically (e.g., planar), the atom to which the bond is attached includes all stereochemical possibilities. When a bond in a compound formula herein is drawn in a defined stereochemical manner (e.g., bold, bold wedge, dashed line, or dashed wedge), it is to be understood that the atom to which the stereochemical bond is attached is enriched in the depicted absolute stereoisomer unless otherwise stated. In one embodiment, the compound may be at least 51% of the depicted absolute stereoisomer. In another embodiment, the compound may be at least 80% of the depicted absolute stereoisomer. In another embodiment, the compound may be at least 90% of the depicted absolute stereoisomer. In another embodiment, the compound may be at least 95% of the depicted absolute stereoisomer. In another embodiment, the compound may be at least 97% of the depicted absolute stereoisomer. In another embodiment, the compound may be at least 98% of the depicted absolute stereoisomer. In another embodiment, the compound may be at least 99% of the depicted absolute stereoisomer.

[0083] The term "alkyl" refers to a monovalent or polyvalent, e.g., monovalent or divalent, straight-chain or branched saturated hydrocarbon group, particularly a hydrocarbon group of 1 to 6 carbon atoms ("Ci-6 alkyl"), e.g., 1, 2, 3, 4, 5, or 6 carbon atoms. In some embodiments, an alkyl group contains 1 to 3 carbon atoms, e.g., 1, 2, or 3 carbon atoms. Some non-limiting examples are methyl (CH3-), ethyl (CH3CH2-), n-propyl (CH3CH2CH2-), 2-propyl (isopropyl, (CH3)2CH2-), n-butyl (CH3CH2CH2CH2-), iso-butyl ((CH3)2CH2CH2-), sec-butyl (CH3CH(CH3)CH2-), and tert-butyl ((CH3)3C-). A preferred, but non-limiting, example of alkyl is tert-butyl ((CH3)3C-) or methyl (CH3-). A preferred, but non-limiting example of alkyl is methyl (CH3-). Another preferred, but non-limiting example of alkyl is tert-butyl ((CH3)3C-).

[0084] The term "alkoxy" refers to an alkyl group, as defined previously, attached to the parent molecular moiety through an oxygen atom. An alkoxy group preferably contains 1 to 6 carbon atoms ("C1-6 alkoxy"), e.g., 1, 2, 3, 4, 5, or 6 carbon atoms. In other embodiments, alkoxy groups contain 1 to 4 carbon atoms. In yet other embodiments, alkoxy groups contain 1 to 3 carbon atoms. Some non-limiting examples of alkoxy groups include CHO-(methoxy), CHCHO-(ethoxy), CHCHCHO-(n-propoxy), and (CH)CO-(tert-butoxy). A particularly preferred, but non-limiting example of alkoxy is methoxy (CHO-).

[0085] The term "halogen" or "halo" refers to fluoro (F), chloro (Cl), bromo (Br), or iodo (I). Preferably, the term "halogen" or "halo" refers to fluoro (F), chloro (Cl), or bromo (Br). Particularly preferred, but non-limiting, examples of "halogen" or "halo" are fluoro (F) and chloro (Cl).

[0086] As used herein, "heteroaryl" refers to a 5- or 6-membered monocyclic aromatic group containing at least one ring heteroatom. In some embodiments, the heteroatom is independently selected from the group consisting of N, O, and S atoms. The number of ring atoms refers to the total number of carbon atoms and heteroatoms in a ring. In some embodiments, the heteroaryl is a 5- or 6-membered monocyclic aromatic group having two N atoms. In some embodiments, the heteroaryl is a 5- or 6-membered monocyclic aromatic group containing one N atom. In some embodiments, the heteroaryl is a 5- or 6-membered monocyclic aromatic group containing one O atom and one S atom. In some embodiments, the heteroaryl is a 5- or 6-membered monocyclic aromatic group containing one N atom and one O atom. Examples of 5-membered heteroaryl groups include, but are not limited to, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, or furanyl. In some preferred embodiments, the 5-membered heteroaryl is pyrazolyl, imidazolyl, oxazolyl, or thiazolyl. Examples of 6-membered heteroaryl groups include, but are not limited to, pyrimidinyl, pyridinyl, pyrazinyl, or pyridazinyl. In some more preferred embodiments, the 6-membered heteroaryl is pyrazinyl, pyridinyl, or pyrimidinyl.

[0087] The term "cyano" refers to a -CN (nitrile) group.

[0088] The terms "hydroxy" or "hydroxyl" refer to an OH group.

[0089] The term "haloalkyl" refers to an alkyl group in which at least one hydrogen atom of the alkyl group is replaced by one or more halogen atoms. Preferably, a "haloalkyl" refers to a C alkyl group in which one, two, or three hydrogen atoms of the alkyl group are replaced by halogen atoms. 1~6 The term "haloalkyl" refers to an alkyl group, i.e., includes monohaloalkyl, dihaloalkyl, trihaloalkyl, perhaloalkyl, etc. The halogen atom may be fluoro (F), chloro (Cl), or bromo (Br). Particularly preferred, but non-limiting examples of "halogen" within haloalkyl are fluoro (F) and chloro (Cl). More preferably, the haloalkyl is substituted with fluoro (F). Preferred, but non-limiting examples of haloalkyl are (CH3)2FC-(1-fluoro-isopropyl), CF3CH2-(2,2,2-trifluoroethyl), CH3CF2-(1,1-difluoroethyl), CF3-(trifluoromethyl), CH2F-(fluoromethyl), or CHF2-(difluoromethyl). CH3CF2- and CF3- are particularly preferred.

[0090] As used herein, "haloalkoxy" refers to an alkoxy group in which at least one hydrogen atom is replaced by a halogen atom. Preferably, "haloalkoxy" refers to an alkoxy group in which one, two, or three hydrogen atoms of the alkyl group are replaced by halogen atoms, preferably C 1~6"Haloalkoxy" refers to an alkoxy group, i.e., haloalkoxy includes monohaloalkoxy, dihaloalkoxy, trihaloalkoxy, perhaloalkoxy, etc. The halogen atom can be fluoro (F), chloro (Cl), or bromo (Br). Particularly preferred, but non-limiting, examples of "halogen" are fluoro (F) and chloro (Cl). More preferably, the haloalkoxy is substituted with fluoro (F). Preferred, but non-limiting, examples of haloalkoxy are CHF2O-, CH2FO-, CF3CHO-, CF2HCHO-, CH3CF2CHO-, and CH3CFHCHO-. Similarly preferred, but non-limiting, examples of haloalkoxy are haloC groups selected from CHF2O-, CH2FO-, CF3O-, FCH2CFHCHO-, CH2FCHO-, and CF3CHO-. 1~6 Particularly preferred are CHF2O-, CF3CH2O-, CF3O-, CH2FO-, or FCH2CFHCH2O-. Haloalkoxy is C 1~6 It may be optionally substituted with alkoxy, for example CF3CH(CH2OCH3)O-.

[0091] The term "hydroxyalkyl" refers to an alkyl group, preferably having 1 to 6 C atoms, in which at least one hydrogen atom of the alkyl group is replaced by one or more hydroxy. Preferably, "hydroxyalkyl" refers to an alkyl group in which 1, 2 or 3 hydrogen atoms of the alkyl group are replaced by hydroxy, preferably C 1~6 It refers to alkyl, i.e., hydroxyalkyl includes monohydroxyalkyl, dihydroxyalkyl, trihydroxyalkyl, perhydroxyalkyl, etc. More preferably, "hydroxyalkyl" refers to an alkyl group in which one hydrogen atom is replaced by hydroxy. Particularly preferred, but non-limiting, examples of hydroxyalkyl are HOCH2-(hydroxymethyl), HOCH2CH2-(hydroxyethyl).

[0092] As used herein, "4- to 6-membered heterocycloalkyl C 0~6 "Alkoxy" is C0~6 It refers to a 4- to 6-membered heterocycloalkyl group bonded to an alkoxy group. C0 is a 4- to 6-membered heterocycloalkyl group. 0~6 The alkoxy group has a "4- to 6-membered heterocycloalkyl-O-" structure. In some embodiments, the heterocycloalkyl ring contains one or more O or S atoms. In some preferred embodiments, the heterocycloalkyl ring contains one O atom. Heterocycloalkyl C according to the present invention 0~6 Non-limiting examples of alkoxy are: [ka]

[0093] As used herein, "3- to 6-membered cycloalkyl C 0~6 "Alkoxy" is C 0~6 It refers to a 3- to 6-membered saturated monocyclic cycloalkyl group bonded to an alkoxy group. C0 is a 3- to 6-membered cycloalkyl C 0~6 The alkoxy group has a "3- to 6-membered cycloalkyl-O-" structure. 0~6 Non-limiting examples of alkoxy are: [ka]

[0094] The term "saturated monocyclic 3- to 6-membered cycloalkyl" refers to a saturated monovalent monocyclic hydrocarbon group of 3 to 6 ring carbon atoms. Examples of such monocyclic cycloalkyls are cyclopropyl, cyclobutanyl, cyclopentyl, or cyclohexyl. Preferred, but non-limiting, examples are cyclopropyl, cyclobutyl, or cyclohexyl. A particularly preferred cycloalkyl is cyclohexyl. Cycloalkyls may be substituted as described herein. Cycloalkyls are preferably unsubstituted.

[0095] The term "4- to 6-membered heterocycloalkyl" refers to a monovalent saturated or partially unsaturated monocyclic or bicyclic ring system of 4 to 6 ring atoms containing 1, 2, or 3 ring heteroatoms independently selected from N, O, and S, with the remaining ring atoms being carbon. A non-limiting example is oxeantyl.

[0096] As used herein, "phenoxy" refers to a phenyl group attached to -O- to form an alkoxy group having the structure "phenyl-O-", optionally substituted as described herein.

[0097] As used herein, the term "mood disorder" refers to a mental health problem that primarily affects a person's emotional state. This is a disorder in which a person experiences prolonged periods of extreme happiness, extreme sadness, or both. Two of the most common mood disorders are depression and bipolar disorder.

[0098] The term "depression" as used herein relates to a mood disorder that causes persistent feelings of sadness and loss of interest, also known as major depressive disorder (MDD).

[0099] The term "behavioral disorder" relates to a disorder that involves a pattern of disruptive behavior in children that lasts for at least six months and causes problems at school, at home and in social situations. "Behavioral disorder" involves a pattern of disruptive behavior in children that lasts for at least six months and causes problems at school, at home and in social situations. The most important behavioral disorder is attention deficit hyperactivity disorder (ADHD).

[0100] As used herein, the term "attention deficit hyperactivity disorder" (ADHD) refers to a behavioral disorder characterized by inattention or hyperactivity and impulsivity. ADHD occurs more frequently in people with epilepsy than in the general population. Children with ADHD are at increased risk of seizures, with approximately 14% of children with ADHD developing seizures.

[0101] As used herein, the term "developmental disorder" or "neurodevelopmental disorder" refers to a group of symptoms caused by impairments in the physical, learning, language, or behavioral domains. These symptoms begin during development, affect daily functioning, and can persist throughout a person's life. Examples of neurodevelopmental disorders include autism spectrum disorders ("ASD") and syndromic developmental disorders.

[0102] As used herein, the term "autism spectrum disorder (ASD)" refers to a range of developmental disorders characterized by difficulties in social interaction and communication, and restricted or repetitive patterns of thought and behavior. ASD is primarily idiopathic, but also encompasses symptomatic forms, and is currently diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Version 5 (DSM V).

[0103] As used herein, the term "symptomatic developmental disorder" refers to a developmental disorder with a clinically defined somatic abnormality pattern and neurobehavioral phenotype, which may include ASD. Diagnosis is typically confirmed by targeted genetic testing. Examples of syndromic developmental disorders include Dup15q syndrome (Dup15q), fragile X syndrome (FXS) and Angelman syndrome.

[0104] As used herein, the term "Dup15q syndrome" or "Duq15q" refers to the common name for chromosome 15q11.2-q13.1 duplication syndrome, a syndromic developmental disorder caused by a partial duplication of chromosome 15 that confers a high risk for autism spectrum disorder, epilepsy, and intellectual disability.

[0105] As used herein, the term "Fragile X Syndrome" (FXS) relates to a genetic disorder characterized by mild to moderate intellectual disability. The disorder is typically caused by an expansion of a CGG triplet repeat in the FMR1 (Fragile X Mental Retardation 1) gene on the X chromosome.

[0106] As used herein, the term "Angelman syndrome" refers to a genetic disorder that primarily affects the nervous system, due to the lack of function of a portion of chromosome 15 inherited from a person's mother. Characteristic features of this condition include developmental delay, intellectual disability, severe speech impairment, and movement and balance problems (ataxia). Most affected children also have recurrent seizures (epilepsy).

[0107] The term "intellectual disability" (ID), as used herein, refers to a generalized neurodevelopmental disorder characterized by significantly impaired intellectual and adaptive functioning. It is defined by an IQ below 70 in addition to two or more adaptive behavioral deficits that affect daily life. ID is also known as general learning disability and was formerly known as mental retardation (MR).

[0108] The term "epilepsy" as used herein refers to a neurological disorder characterized by sudden recurrent episodes of sensory disturbances, loss of consciousness, or convulsions associated with abnormal electrical activity in the brain. Examples of epilepsy include diffuse childhood epilepsy, West syndrome, Ohtahara syndrome, and epileptic encephalopathy.

[0109] The term "neurodegenerative disease" as used herein refers to a disease associated with the progressive loss of neuronal structure or function, including neuronal death. Examples of neurodegenerative diseases include, but are not limited to, Alzheimer's disease and motor neuron disease.

[0110] As used herein, the term "motor neuron disease" refers to a group of rare neurodegenerative disorders that selectively affect motor neurons. Examples of motor neuron diseases include, but are not limited to, amyotrophic lateral sclerosis (ALS).

[0111] The term "pain" as used herein refers to an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Examples of pain include, but are not limited to, nociceptive pain, chronic pain (including idiopathic pain), neuropathic pain, including chemotherapy-induced neuropathy, phantom limb pain, and psychogenic pain.

[0112] The term "migraine" as used herein relates to a moderate to severe headache disorder that causes throbbing or throbbing pain for hours or days.

[0113] The term "tinnitus" as used herein relates to a condition characterized by the perception of sound in the absence of a corresponding external sound.

[0114] Any disease, disorder or disability referred to herein also includes any condition or symptom associated with such disease, disorder or disability.

[0115] Compounds of the Invention All compound names for compound structures were generated using OpenEye Lexichem, version 1.2.0, OpenEye Scientific Software, Santa Fe, NM, USA; www.eyesopen.com .

[0116] It should be understood that any feature, integer, characteristic, compound, chemical moiety, or group described in connection with a particular aspect, embodiment, or example of the invention is applicable to any other aspect, embodiment, or example described herein, except where inconsistent therewith. All features disclosed herein (including any accompanying claims, abstract, and drawings), and / or all steps of any method or process so disclosed, may be combined in any combination, except combinations in which at least some of such features and / or steps are mutually exclusive. The invention is not limited to the details of any embodiment described herein. Any embodiment described in this application may be combined with any other embodiment. For example, any embodiment herein relating to a compound of the invention may be combined with any embodiment of a pharmaceutical composition, kit, medical use, or method of treatment. The invention extends to any novel one or any novel combination of features disclosed herein (including any accompanying claims, abstract, and drawings), or any novel one or any novel combination of steps of any method or process so disclosed.

[0117] In some embodiments of the present invention, the compound of formula (I') or (I) has a structure as shown in any of formulas (II'), (I*), (II**), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), or (XI). The present invention relates to a compound of formula (I') [ka] (In the formula, A 1 is N or CH, A 2 is N or CH, A 3 is N or CH, provided that A 1 , A 2 , or A 3 at least one of is N, R1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, and heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkyloxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 Optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy and haloC 1~6 Alkoxy is C 1~6 optionally substituted with alkoxy; R 2 H, D, and C 1~6 alkyl, R 3 is H, C 1~6 is alkyl, R 4 is H or a halogen, R 5 is H or a halogen, R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen; R 8 H, D, and C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0118] In one embodiment, the present invention provides a compound of formula (I) [ka] (In the formula, A 1 is N or CH, A 2 is N or CH, A 3 is N or CH, provided that A 1 , A 2 , or A 3 at least one of is N, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 Optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy and haloC 1~6 Alkoxy is C 1~6 optionally substituted with alkoxy; R 2 is H or C 1~6 is alkyl, R 3 is H or C 1~6 is alkyl, R 4 is H or a halogen, R 5 is H or a halogen, R 6is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0119] In one embodiment, the present invention provides a compound of formula (I) [ka] (In the formula, A 1 is N or CH, A 2 is N or CH, A 3 is N or CH, provided that A 1 , A 2 , or A 3 at least one of is N, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 2 is H or C 1~6 is alkyl, R 3 is H or C 1~6 is alkyl, R 4 is H or a halogen, R 5 is H or a halogen, R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0120] In one embodiment, the present invention provides a compound of formula (II) [ka] (In the formula, A 1 is N or CH, A 2 is N or CH, A 3 is N or CH, provided that A 1 , A 2 , or A 3 at least one of is N, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, and heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkyloxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0121] In one embodiment, the present invention provides a compound of formula (II') [ka] (In the formula, A 1 is N or CH, A 2 is N or CH, A 3 is N or CH, provided that A 1 , A 2 , or A 3 at least one of is N, R1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, and heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkyloxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 Optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy and haloC 1~6 Alkoxy is C 1~6 optionally substituted with alkoxy; R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0122] All of the features disclosed in this specification (including any accompanying claims, abstracts, and drawings) for any embodiment so disclosed may be combined in any combination, except combinations in which at least some of such features and / or steps are mutually exclusive. The present invention is not limited to the details of any embodiment described herein. Any embodiment described in this application may be combined with any other embodiment.

[0123] In one embodiment, the present invention provides a compound of formula (I') [ka] (In the formula, A 1 is N or CH, A 2 is N or CH, A 3 is N or CH, provided that A 1 , A 2 , or A 3 at least one of is N), or a solvate or pharmaceutically acceptable salt thereof.

[0124] In one embodiment, the present invention provides a compound of formula (I) [ka] (In the formula, A 1 is N or CH, A 2 is N or CH, A 3 is N or CH, provided that A 1 , A 2 , or A 3 at least one of is N), or a solvate or pharmaceutically acceptable salt thereof.

[0125] In the present invention, A in the compound of formula (I') or (I), or a solvate or pharmaceutically acceptable salt thereof 1 , A 2 , A 3 cannot be a CH at the same time.

[0126] In one embodiment, the present invention provides a 1 , A 2 , or A 3wherein one, two or three of are N, or a solvate or pharmaceutically acceptable salt thereof.

[0127] In one embodiment, the present invention provides a 1 , A 2 , or A 3 is N. In this embodiment, the other is CH.

[0128] In one preferred embodiment, the present invention provides a 1 In this embodiment, the compound of formula (I') or (I), or a solvate or pharmaceutically acceptable salt thereof, is provided, wherein only A is N. 2 and A 3 is CH.

[0129] In one embodiment, the present invention provides a 2 In this embodiment, the compound of formula (I') or (I), or a solvate or pharmaceutically acceptable salt thereof, is provided, wherein only A is N. 1 and A 3 is CH.

[0130] In one embodiment, the present invention provides a 3 In this embodiment, the compound of formula (I') or (I), or a solvate or pharmaceutically acceptable salt thereof, is provided, wherein only A is N. 1 and A 2 is CH.

[0131] In one embodiment, the present invention provides a 1 , A 2 , or A 3 and n is 0, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 39, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,

[0132] In one embodiment, the present invention provides a 1and A 2 In this embodiment, the compound of formula (I') or (I), or a solvate or pharmaceutically acceptable salt thereof, is provided, wherein only A is N. 3 is CH.

[0133] In one embodiment, the present invention provides a 1 and A 3 In this embodiment, the compound of formula (I') or (I), or a solvate or pharmaceutically acceptable salt thereof, is provided, wherein only A is N. 2 is CH.

[0134] In one embodiment, the present invention provides a 2 and A 3 In this embodiment, the compound of formula (I') or (I), or a solvate or pharmaceutically acceptable salt thereof, is provided, wherein only A is N. 1 is CH.

[0135] In one embodiment, the present invention provides a 1 , A 2 , and A 3 is N, or a solvate or pharmaceutically acceptable salt thereof.

[0136] In the present invention, the compound of formula (I') or (I), or a solvate or a pharmaceutically acceptable salt thereof, 1 , A 2 , or A 3 at least one of which is N, and the others are CH, CR as described herein; * , C.R. ** , and C.R. *** are independently selected from

[0137] In some embodiments, the present invention provides a method for treating a cancer comprising administering to a patient a cancer-containing compound comprising: * , R ** , or R *** are all halogens, haloC 1~6 Alkyl and halo 1~6The present invention provides a compound of formula (I') or (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0138] In some embodiments, the present invention provides a compound of formula (I') [ka] (In the formula, A 1 is N, CH, or CR * and A 2 is N, CH, or CR ** and A 3 is N, CH, or CR *** However, A 1 , A 2 , or A 3 at least one of is N, R * , R ** , or R *** is halogen, halo C 1~6 Alkyl and haloC 1~6 independently selected from alkoxy; R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, and heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkyloxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 Optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy and haloC 1~6 Alkoxy is C 1~6 optionally substituted with alkoxy; R2 H, D, and C 1~6 alkyl, R 3 is H or C 1~6 is alkyl, R 4 is H or a halogen, R 5 is H or a halogen, R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen; R 8 H, D, and C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0139] In some embodiments, the present invention provides a compound of formula (I) [ka] (In the formula, A 1 is N, CH, or CR * and A 2 is N, CH, or CR ** and A 3 is N, CH, or CR *** However, A 1 , A 2 , or A 3 at least one of is N, R* , R ** , or R *** is halogen, halo C 1~6 Alkyl and haloC 1~6 independently selected from alkoxy; R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, and heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkyloxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 Optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy and haloC 1~6 Alkoxy is C 1~6 optionally substituted with alkoxy; R 2 is H or C 1~6 is alkyl, R 3 is H or C 1~6 is alkyl, R 4 is H or a halogen, R 5 is H or a halogen, R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0140] In some embodiments, the present invention provides a compound of formula (I) [ka] (In the formula, A 1 is N, CH, or CR * and A 2 is N, CH, or CR ** and A 3 is N, CH, or CR *** However, A 1 , A 2 , or A 3 at least one of is N, R * , R ** , or R *** is halogen, halo C 1~6 Alkyl and haloC 1~6 independently selected from alkoxy; R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, and heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkyloxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 2 is H or C 1~6 is alkyl, R 3 is H or C 1~6 is alkyl, R 4 is H or a halogen, R 5 is H or a halogen, R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0141] In one embodiment, the present invention provides a compound comprising R 1 But, Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 4-6 membered cycloalkylC 0~6 Alkoxy, phenoxy, 4- to 6-membered heterocycloalkyl, and 4- to 6-membered heterocycloalkylC 0~6 alkoxy, heteroaryl, heterocycloalkyl, heterocycloalkylalkoxy, cycloalkylalkoxy or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 Provided are compounds of formula (I), or solvates or pharmaceutically acceptable salts thereof, optionally substituted with one, two or three substituents independently selected from alkoxy.

[0142] In one embodiment, the present invention provides a compound comprising R1 cyano, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, 4-6 membered cycloalkylC 0~6 Alkoxy, phenoxy, 4- to 6-membered heterocycloalkyl, and 4- to 6-membered heterocycloalkylC 0~6 alkoxy, heteroaryl, heterocycloalkyl, heterocycloalkylalkoxy, cycloalkylalkoxy or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 Provided are compounds of formula (I), or solvates or pharmaceutically acceptable salts thereof, optionally substituted with one, two or three substituents independently selected from alkoxy.

[0143] In one embodiment, the present invention provides a compound comprising R 1 cyano, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, 4-6 membered cycloalkylC 0~6 Alkoxy, phenoxy, 4- to 6-membered heterocycloalkyl, and 4- to 6-membered heterocycloalkylC 0~6 alkoxy, heteroaryl, heterocycloalkyl, heterocycloalkylalkoxy, cycloalkylalkoxy, or phenoxy, selected from one haloC 1~6 Provided are compounds of formula (I), or solvates or pharmaceutically acceptable salts thereof, optionally substituted with alkyl.

[0144] In one embodiment, the present invention provides a compound comprising R 1 But one halo C 1~6 5-membered heteroaryl, 4- to 6-membered cycloalkyl optionally substituted with alkyl 0~6 Alkoxy, phenoxy, 4- to 6-membered heterocycloalkyl, and 4- to 6-membered heterocycloalkylC 0~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0145] In one embodiment, the present invention provides a compound comprising R1 is one haloC selected from (CH3)2CF-, CH3CF2-, CF3-, CH2F-, and CHF2- 1~6 5-membered heteroaryl, 4- to 6-membered cycloalkyl optionally substituted with alkyl 0~6 Alkoxy, phenoxy, 4- to 6-membered heterocycloalkyl, and 4- to 6-membered heterocycloalkylC 0~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0146] In one embodiment, the present invention provides a compound comprising R 1 5-membered heteroaryl optionally substituted with one CF3-, 4- to 6-membered cycloalkylC 0~6 Alkoxy, phenoxy, 4- to 6-membered heterocycloalkyl, and 4- to 6-membered heterocycloalkylC 0~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0147] In one preferred embodiment, the present invention provides a compound comprising R 1 is cyano, or a solvate or pharmaceutically acceptable salt thereof.

[0148] In one preferred embodiment, the present invention provides a compound comprising R 1 is a halogen selected from F-, Cl-, or Br-, or a solvate or pharmaceutically acceptable salt thereof.

[0149] In one preferred embodiment, the present invention provides a compound comprising R 1 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0150] In one more preferred embodiment, the present invention provides a compound comprising R 1 is Cl-, or a solvate or pharmaceutically acceptable salt thereof.

[0151] In one preferred embodiment, the present invention provides a compound comprising R 1 is a 5-membered heteroaryl which is a 5-membered monocyclic aromatic group having two N atoms, such as pyrazolyl or imidazolyl, or a solvate or pharmaceutically acceptable salt thereof.

[0152] In one preferred embodiment, the present invention provides a compound comprising R 1 is a 5-membered heteroaryl, which is a 5-membered monocyclic aromatic group containing one N atom and one O atom, e.g., oxazolyl, or a solvate or pharmaceutically acceptable salt thereof.

[0153] In one preferred embodiment, the present invention provides a compound comprising R 1 is a 5-membered heteroaryl, e.g., thiazolyl, which is a 5-membered monocyclic aromatic group containing one N atom and one S atom, or a solvate or pharmaceutically acceptable salt thereof.

[0154] In one preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein the 5-membered heteroaryl is selected from pyrazolyl, imidazolyl, oxazolyl, and thiazolyl, optionally substituted as described herein.

[0155] In one preferred embodiment, the present invention provides a 5-membered heteroaryl selected from pyrazolyl, imidazolyl, oxazolyl, and thiazolyl, wherein the pyrazolyl, imidazolyl, oxazolyl, or thiazolyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 Provided are compounds of formula (I), or solvates or pharmaceutically acceptable salts thereof, optionally substituted with one, two, or three substituents independently selected from alkoxy.

[0156] In one preferred embodiment, the present invention provides a 5-membered heteroaryl selected from pyrazolyl, imidazolyl, oxazolyl, and thiazolyl, wherein the pyrazolyl, imidazolyl, oxazolyl, or thiazolyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, optionally substituted with one substituent selected from alkoxy.

[0157] In one preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein the 5-membered heteroaryl is selected from pyrazolyl, imidazolyl, oxazolyl, and thiazolyl, and the pyrazolyl, imidazolyl, oxazolyl, or thiazolyl is unsubstituted.

[0158] In some embodiments, the halogens in the substituents are selected from F − , Cl − , and Br − .

[0159] In some embodiments, the halogen in the substituent is F— or Cl—.

[0160] In some preferred embodiments, the halogen in the substituent is Cl-.

[0161] In some embodiments, the halo C 1~6 Alkyl is selected from (CH3)2CF-, CH3CF2-, CF3-, CH2F-, and CHF2-.

[0162] In some embodiments, the halo C 1~6 The alkyl is CF3-.

[0163] In some embodiments, the halo C 1~6 Alkoxy is selected from CHF2O-, CH2FO-, CF3CH2O-, CF2HCH2O-, CH3CF2CH2O-, and CH3CFHCH2O.

[0164] In some embodiments, the halo C 1~6 Alkoxy is CHF2O- or CF3CH2O-.

[0165] In some preferred embodiments, the halo C 1~6 The alkoxy is CHF2O-.

[0166] In one preferred embodiment, the present invention provides a compound comprising R 1 is unsubstituted pyrazolyl, or a solvate or pharmaceutically acceptable salt thereof.

[0167] In one embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, which is pyrazolyl substituted with 1, 2, or 3 substituents independently selected from alkoxy.

[0168] In one embodiment, the present invention provides a compound comprising R 1 is pyrazolyl substituted with one halogen selected from F-, Cl-, and Br-, or a solvate or pharmaceutically acceptable salt thereof.

[0169] In one embodiment, the present invention provides a compound comprising R 1 is pyrazolyl substituted with one F-, or a solvate or pharmaceutically acceptable salt thereof.

[0170] In one preferred embodiment, the present invention provides a compound comprising R 1 is pyrazolyl substituted with one Cl-, or a solvate or pharmaceutically acceptable salt thereof.

[0171] In one embodiment, the present invention provides a compound comprising R 1 is one haloC selected from (CH3)2CF-, CH3CF2-, CF3-, CH2F-, and CHF2-1~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, which is alkyl-substituted pyrazolyl.

[0172] In one preferred embodiment, the present invention provides a compound comprising R 1 is pyrazolyl substituted with one CF3-, or a solvate or pharmaceutically acceptable salt thereof.

[0173] In one embodiment, the present invention provides a compound comprising R 1 is one haloC selected from CHF2O-, CH2FO-, CF3CH2O-, CF2HCH2O-, CH3CF2CH2O-, and CH3CFHCH2O 1~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, which is pyrazolyl substituted with alkoxy.

[0174] In one preferred embodiment, the present invention provides a compound comprising R 1 is unsubstituted imidazolyl, or a solvate or pharmaceutically acceptable salt thereof.

[0175] In one embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, which is imidazolyl substituted with one, two, or three substituents independently selected from alkoxy.

[0176] In one embodiment, the present invention provides a compound comprising R 1 is imidazolyl substituted with one halogen selected from F-, Cl-, and Br-, or a solvate or pharmaceutically acceptable salt thereof.

[0177] In one embodiment, the present invention provides a compound comprising R 1is imidazolyl substituted with one F-, or a solvate or pharmaceutically acceptable salt thereof.

[0178] In one preferred embodiment, the present invention provides a compound comprising R 1 is imidazolyl substituted with one Cl-, or a solvate or pharmaceutically acceptable salt thereof.

[0179] In one embodiment, the present invention provides a compound comprising R 1 is one haloC selected from (CH3)2CF-, CH3CF2-, CF3-, CH2F-, and CHF2- 1~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, which is an alkyl-substituted imidazolyl.

[0180] In one preferred embodiment, the present invention provides a compound comprising R 1 is imidazolyl substituted with one CF3-, or a solvate or pharmaceutically acceptable salt thereof.

[0181] In one embodiment, the present invention provides a compound comprising R 1 is one haloC selected from CHF2O-, CH2FO-, CF3CH2O-, CF2HCH2O-, CH3CF2CH2O-, and CH3CFHCH2O 1~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, which is an imidazolyl substituted with alkoxy.

[0182] In one preferred embodiment, the present invention provides a compound comprising R 1 is unsubstituted oxazolyl, or a solvate or pharmaceutically acceptable salt thereof.

[0183] In one embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, which is oxazolyl substituted with one, two, or three substituents independently selected from alkoxy.

[0184] In one embodiment, the present invention provides a compound comprising R 1 is oxazolyl substituted with one halogen selected from F-, Cl-, and Br-, or a solvate or pharmaceutically acceptable salt thereof.

[0185] In one embodiment, the present invention provides a compound comprising R 1 is oxazolyl substituted with one F-, or a solvate or pharmaceutically acceptable salt thereof.

[0186] In one preferred embodiment, the present invention provides a compound comprising R 1 is oxazolyl substituted with one Cl-, or a solvate or pharmaceutically acceptable salt thereof.

[0187] In one embodiment, the present invention provides a compound comprising R 1 is one haloC selected from (CH3)2CF-, CH3CF2-, CF3-, CH2F-, and CHF2- 1~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, which is an alkyl-substituted oxazolyl.

[0188] In one preferred embodiment, the present invention provides a compound comprising R 1 is oxazolyl substituted with one CF3-, or a solvate or pharmaceutically acceptable salt thereof.

[0189] In one embodiment, the present invention provides a compound comprising R 1 is one haloC selected from CHF2O-, CH2FO-, CF3CH2O-, CF2HCH2O-, CH3CF2CH2O-, and CH3CFHCH2O 1~6Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, which is an oxazolyl substituted with alkoxy.

[0190] In one preferred embodiment, the present invention provides a compound comprising R 1 is unsubstituted thiazolyl, or a solvate or pharmaceutically acceptable salt thereof.

[0191] In one embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, which is thiazolyl substituted with 1, 2, or 3 substituents independently selected from alkoxy.

[0192] In one embodiment, the present invention provides a compound comprising R 1 is thiazolyl substituted with one halogen selected from F-, Cl-, and Br-, or a solvate or pharmaceutically acceptable salt thereof.

[0193] In one embodiment, the present invention provides a compound comprising R 1 is thiazolyl substituted with one F-, or a solvate or pharmaceutically acceptable salt thereof.

[0194] In one preferred embodiment, the present invention provides a compound comprising R 1 is thiazolyl substituted with one Cl-, or a solvate or pharmaceutically acceptable salt thereof.

[0195] In one embodiment, the present invention provides a compound comprising R 1 is one haloC selected from (CH3)2CF-, CH3CF2-, CF3-, CH2F-, and CHF2- 1~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, which is an alkyl-substituted thiazolyl.

[0196] In one preferred embodiment, the present invention provides a compound comprising R 1 is thiazolyl substituted with one CF3-, or a solvate or pharmaceutically acceptable salt thereof.

[0197] In one embodiment, the present invention provides a compound comprising R 1 is one haloC selected from CHF2O-, CH2FO-, CF3CH2O-, CF2HCH2O-, CH3CF2CH2O-, and CH3CFHCH2O 1~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, which is thiazolyl substituted with alkoxy.

[0198] In one embodiment, the present invention provides a compound comprising R 1 C 1~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein: R is alkoxy;

[0199] In one embodiment, the present invention provides a compound comprising R 1 is selected from CHO-, CHCHO-, CHCHCHO-, (CH)CHO-, and (CH)CO- 1~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein: R is alkoxy;

[0200] In one embodiment, the present invention provides a compound comprising R 1 is CH3O- or (CH3)2CHO-, or a solvate or pharmaceutically acceptable salt thereof.

[0201] In one embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 3- to 6-membered cycloalkylC optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy 0~6Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein: R is alkoxy; In one embodiment, the present invention provides a compound comprising R 1 is a 3- to 6-membered cycloalkyl C selected from the following 0~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein: R is alkoxy; [ka]

[0202] In one embodiment, the present invention provides a compound comprising R 1 is a 3- to 6-membered cycloalkyl C having the following structure: 0~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein: R is alkoxy; [ka]

[0203] In one embodiment, the present invention provides a compound comprising R 1 is a 3- to 6-membered cycloalkyl C having the following structure: 0~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein: R is alkoxy; [ka]

[0204] In one embodiment, the present invention provides a compound comprising R 1 is a 4- to 6-membered heterocycloalkylC optionally substituted as described herein 0~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein: R is alkoxy;

[0205] In one embodiment, the present invention provides a compound comprising R 1 is an unsubstituted 4- to 6-membered heterocycloalkylC 0~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein: R is alkoxy;

[0206] In one embodiment, the present invention provides a compound comprising R 1 is a 4- to 6-membered heterocycloalkyl selected from the following: 0~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein: R is alkoxy; [ka]

[0207] In one embodiment, the present invention provides a compound comprising R 1 is a 4- to 6-membered heterocycloalkyl selected from the following: 0~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein: R is alkoxy; [ka]

[0208] In one embodiment, the present invention provides a compound comprising R 1 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, having the structure: [ka]

[0209] In one embodiment, the present invention provides a compound comprising R 1 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, having the structure: [ka]

[0210] In one embodiment, the present invention provides a compound comprising R 1 is phenoxy, or a solvate or pharmaceutically acceptable salt thereof.

[0211] In one embodiment, the present invention provides a compound comprising R 1 But halogen, halo C1~6 Alkyl and haloC 1~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, which is phenoxy optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy.

[0212] In one embodiment, the present invention provides a compound comprising R 1 is phenoxy optionally substituted as described herein, and halogen is selected from F— and Cl—, or a solvate or pharmaceutically acceptable salt thereof.

[0213] In one embodiment, the present invention provides a compound comprising R 1 is phenoxy optionally substituted as described herein, and haloC 1~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein alkyl is selected from (CH3)2FC-, CF3CH2-, CH3CF2-, CF3-, CH2F-, and CHF2-.

[0214] In one embodiment, the present invention provides a compound comprising R 1 is phenoxy optionally substituted as described herein, and haloC 1~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein alkoxy is selected from CHF2O-, CF3O-, FCH2CFHCH2O-, and CF3CH2O-.

[0215] In one embodiment, the present invention provides a compound comprising R 1 is phenoxy optionally substituted with one CF3-, Cl-, or F-, or a solvate or pharmaceutically acceptable salt thereof.

[0216] In one embodiment, the present invention provides a compound comprising R 1 is unsubstituted phenoxy, or a solvate or pharmaceutically acceptable salt thereof.

[0217] In one embodiment, the present invention provides a compound comprising R 1 is unsubstituted phenoxy having the following structure: or a solvate or pharmaceutically acceptable salt thereof. [ka]

[0218] In one preferred embodiment, the present invention provides a compound comprising R 1 Halo C 1~6 Alkoxy or HaloC 1~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0219] In one preferred embodiment, the present invention provides a compound comprising R 1 is a haloC selected from CHF2O-, CH2FO-, CF3O-, FCH2CFHCH2O-, CH2FCH2O-, CH2FCH2O-, and CF3CH2O- 1~6 The compound of formula (I) is provided, wherein the compound is alkoxy.

[0220] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is CH2FO-.

[0221] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is CF3O-.

[0222] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is FCH2CFHCH2O-.

[0223] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is CF3CH2O-.

[0224] In one particularly preferred embodiment, the present invention provides a compound comprising R 1is CHF2O-.

[0225] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is CH2FCH2O-.

[0226] In one embodiment, the present invention provides a compound comprising R 1 is C as defined herein 1~6 haloC as defined herein optionally substituted with alkoxy 1~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein: R is alkoxy;

[0227] In one embodiment, the present invention provides a compound comprising R 1 is C as defined herein 1~6 haloC as defined herein substituted with alkoxy 1~6 Provided is a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein: R is alkoxy;

[0228] In one embodiment, the present invention provides a compound comprising R 1 But C 1~6 Alkoxy-substituted haloC 1~6 The present invention provides a compound of formula (I) wherein R is alkoxy and has the following structure: or a solvate or pharmaceutically acceptable salt thereof. [ka]

[0229] In one preferred embodiment, the present invention provides a compound comprising R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0230] In one preferred embodiment, the present invention provides a compound comprising R 2 C 1~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0231] In the present invention, R in the compound of formula (I) 2 But H or C 1~6 If it is alkyl, the other substituent at this C atom is H.

[0232] In one preferred embodiment, the present invention provides a compound comprising R 2 is selected from CH3-, CH3CH2-, CH3CH2CH2-, (CH3)2CH2-, (CH3CH2CH2CH2-), (CH3)2CH2CH2-, CH3CH(CH3)CH2-, and (CH3)3C- 1~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0233] In one preferred embodiment, the present invention provides a compound comprising R 2 is CH3-, or a solvate or pharmaceutically acceptable salt thereof.

[0234] In one embodiment, the present invention provides a compound comprising R 1 But, Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with one, two, or three substituents independently selected from alkoxy; 2 is H or C as described herein 1~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0235] In one preferred embodiment, the present invention provides a compound comprising R 1 But, Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with one, two, or three substituents independently selected from alkoxy; 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0236] In one preferred embodiment, the present invention provides a compound comprising R 1 But, Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is unsubstituted; R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0237] In one preferred embodiment, the present invention provides a compound comprising R 1 is a halogen and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0238] In one preferred embodiment, the present invention provides a compound comprising R 1 is Cl- and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0239] In one preferred embodiment, the present invention provides a compound comprising R 1 is cyano and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0240] In one preferred embodiment, the present invention provides a compound comprising R 1 is a 5-membered heteroaryl optionally substituted as described herein, and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0241] In one preferred embodiment, the present invention provides a compound comprising R 1 is a 5-membered heteroaryl selected from pyrazolyl, imidazolyl, oxazolyl, and thiazolyl, optionally substituted as described herein; R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0242] In one preferred embodiment, the present invention provides a compound comprising R 1 is a 5-membered heteroaryl selected from pyrazolyl, imidazolyl, oxazolyl, and thiazolyl, wherein the pyrazolyl, imidazolyl, oxazolyl, or thiazolyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 Optionally substituted with one substituent selected from alkoxy, R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0243] In some embodiments of the above, the halogen in the substituent is selected from F, Cl, and Br; and R 2 is H.

[0244] In some of the above embodiments, the halogen in the substituent is F— or Cl—, and R 2 is H.

[0245] In some of the above embodiments, the halogen in the substituent is Cl— and R 2 is H.

[0246] In some embodiments of the above, halo C 1~6 alkyl is selected from (CH3)2CF—, CH3CF2—, CF3—, CH2F—, and CHF2—; R 2 is H.

[0247] In some embodiments of the above, halo C 1~6 alkyl is CF3-, and R 2 is H.

[0248] In some embodiments, the halo C 1~6 alkoxy is selected from CHF2O-, CH2FO-, CF3O-, FCH2CFHCH2O-, CH2FCH2O-, and CF3CH2O-; R 2 is H.

[0249] In some embodiments of the above, halo C 1~6 Alkoxy is CHF2O- or CF3CH2O-, and R 2 is H.

[0250] In some preferred embodiments of the above, halo C 1~6 Alkoxy is CHF2O-, CH2FO-, CF3O-, FCH2CFHCH2O-, CH2FCH2O-, and R 2 is H.

[0251] In some preferred embodiments of the above, halo C 1~6 Alkoxy is CHF2O-, and R 2 is H.

[0252] In some preferred embodiments of the above, halo C 1~6 Alkoxy is CH2FO-, and R 2 is H.

[0253] In some preferred embodiments of the above, halo C 1~6 Alkoxy is CF3O-, and R 2 is H.

[0254] In some preferred embodiments of the above, halo C 1~6 Alkoxy is FCHCFHCHO-, and R 2 is H.

[0255] In some preferred embodiments of the above, halo C 1~6 Alkoxy is CH2FCH2O-, and R 2 is H.

[0256] In one preferred embodiment, the present invention provides a compound comprising R 1 is an unsubstituted 5-membered heteroaryl selected from pyrazolyl, imidazolyl, oxazolyl, and thiazolyl; R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0257] In one preferred embodiment, the present invention provides a compound comprising R 1 is unsubstituted pyrazolyl, and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0258] In one preferred embodiment, the present invention provides a compound comprising R 1 is unsubstituted imidazolyl, and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0259] In one preferred embodiment, the present invention provides a compound comprising R 1is unsubstituted oxazolyl, and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0260] In one preferred embodiment, the present invention provides a compound comprising R 1 is unsubstituted thiazolyl, and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0261] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 Halo C 1~6 is alkoxy, and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0262] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is a halo group selected from CHF2O-, CH2FO-, CF3O-, FCH2CFHCH2O-, and CH2FCH2O- 1~6 is alkoxy, and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0263] In some embodiments, halo C 1~6 Alkoxy is C as described herein 1~6 It is substituted with alkoxy.

[0264] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is CHF2O- and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0265] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is CH2FO- and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0266] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is CF3O- and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0267] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is FCH2CFHCH2O- and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0268] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is CH2FCH2O-, and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0269] In one preferred embodiment, the present invention provides a compound comprising R 1 Halo C 1~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0270] In one preferred embodiment, the present invention provides a compound comprising R 1 is a haloC selected from (CH3)2FC-, CF3CH2-, CH3CF2-, CF3-, CH2F-, and CHF2- 1~6 alkyl, and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0271] In one preferred embodiment, the present invention provides a compound comprising R 1 is (CH3)2FC- and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0272] In one preferred embodiment, the present invention provides a compound comprising R 1is CF3CH2- and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0273] In one preferred embodiment, the present invention provides a compound comprising R 1 is CH3CF2- and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0274] In one preferred embodiment, the present invention provides a compound comprising R 1 is CF3- and CHF2-, and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0275] In one preferred embodiment, the present invention provides a compound comprising R 1 is CHF2- and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0276] In one preferred embodiment, the present invention provides a compound comprising R 1 4-6 membered heterocycloalkylC 0~6 is alkoxy, and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0277] In one preferred embodiment, the present invention provides a compound comprising R 1 is a 4- to 6-membered heterocycloalkylC selected from the following: 0~6 Alkoxy [ka] and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0278] In one preferred embodiment, the present invention provides a compound comprising R1 but [ka] and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0279] In one preferred embodiment, the present invention provides a compound comprising R 1 but [ka] and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0280] In one preferred embodiment, the present invention provides a compound comprising R 1 but [ka] and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0281] In one embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 phenoxy optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0282] In one embodiment, the present invention provides a compound comprising R 1 is unsubstituted phenoxy, and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0283] In one embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 3- to 6-membered cycloalkylC optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy 0~6 is alkoxy, and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0284] In one embodiment, the present invention provides a compound comprising R 1 is a 3- to 6-membered cycloalkyl C selected from the following 0~6 Alkoxy [ka] and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0285] In one embodiment, the present invention provides a compound comprising R 1 is a 3- to 6-membered cycloalkyl C having the following structure: 0~6 Alkoxy [ka] and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0286] In one embodiment, the present invention provides a compound comprising R 1 is a 3- to 6-membered cycloalkyl C having the following structure: 0~6 Alkoxy [ka] and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0287] In one embodiment, the present invention provides a compound comprising R 1 is a 4-6 membered heterocycloalkyl optionally substituted as described herein; R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0288] In one embodiment, the present invention provides a compound comprising R 1 is an unsubstituted 4- to 6-membered heterocycloalkyl, and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0289] In one embodiment, the present invention provides a compound comprising R 1 is a 4- to 6-membered heterocycloalkyl selected from the following: [ka] and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0290] In one embodiment, the present invention provides a compound comprising R 1 but [ka] and R 2 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0291] In one embodiment, the present invention provides a compound comprising R 1 Both are described herein. 1~6 Alkyl or haloC 1~6 is alkoxy, and R 2 C as described herein 1~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0292] In one embodiment, the present invention provides a compound comprising R1 Both are described herein. 1~6 Alkyl or haloC 1~6 is alkoxy, and R 2 is CH3-, or a solvate or pharmaceutically acceptable salt thereof.

[0293] In one embodiment, the present invention provides a compound comprising R 3 is H or C 1~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0294] In one preferred embodiment, the present invention provides a compound comprising R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0295] In one embodiment, the present invention provides a compound comprising R 3 C 1~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0296] In one embodiment, the present invention provides a compound comprising R 3 is CH3-, or a solvate or pharmaceutically acceptable salt thereof.

[0297] In one embodiment, the present invention provides a compound comprising R 1 But, Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6optionally substituted with one, two, or three substituents independently selected from alkoxy; 2 is H and R 3 is selected from CH3-, CH3CH2-, CH3CH2CH2-, (CH3)2CH2-, (CH3CH2CH2CH2-), (CH3)2CH2CH2-, CH3CH(CH3)CH2-, and (CH3)3C- 1~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0298] In one embodiment, the present invention provides a compound comprising R 1 But, Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with one, two, or three substituents independently selected from alkoxy; 2 is H and R 3 is CH3-, or a solvate or pharmaceutically acceptable salt thereof.

[0299] In one embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 is alkoxy, and R 2 is H and R 3 is CH3-, or a solvate or pharmaceutically acceptable salt thereof.

[0300] In one preferred embodiment, the present invention provides a compound comprising R 1 But, Cyano, Halo C 1~6Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with one, two, or three substituents independently selected from alkoxy; 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0301] In one embodiment, the present invention provides a compound comprising R 1 is cyano and R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0302] In one preferred embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 alkyl, and R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0303] In one preferred embodiment, the present invention provides a compound comprising R 1 is a halogen as described herein, and R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0304] In one preferred embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6Alkyl and haloC 1~6 5-membered heteroaryl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0305] In one preferred embodiment, the present invention provides a compound comprising R 1 C as described herein 1~6 alkyl, and R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0306] In one preferred embodiment, the present invention provides a compound comprising R 1 C as described herein 1~6 is alkoxy, and R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0307] In one preferred embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 3- to 6-membered cycloalkylC optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy 0~6 is alkoxy, and R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0308] In one preferred embodiment, the present invention provides a compound comprising R 1 is unsubstituted 3- to 6-membered cycloalkyl C 0~6 is alkoxy, and R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0309] In one preferred embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 R is a 4- to 6-membered heterocycloalkyl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0310] In one preferred embodiment, the present invention provides a compound comprising R 1 is an unsubstituted 4- to 6-membered heterocycloalkyl, and R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0311] In one preferred embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 4- to 6-membered heterocycloalkyl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; 0~6 is alkoxy, and R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0312] In one preferred embodiment, the present invention provides a compound comprising R 1 is unsubstituted 4-6 membered heterocycloalkyl C 0~6 is alkoxy, and R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0313] In one preferred embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6Alkyl and haloC 1~6 phenoxy optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0314] In one preferred embodiment, the present invention provides a compound comprising R 1 is unsubstituted phenoxy, and R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0315] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 is alkoxy, and R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0316] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is a haloC selected from CHF2O-, CH2FO-, CF3O-, FCH2CFHCH2O-, CH2FCH2O-, and CF3CH2O- 1~6 is alkoxy, and R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0317] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 HaloC is CHF2O- 1~6 is alkoxy, and R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0318] In one particularly preferred embodiment, the present invention provides a compound comprising R1 is CH2FO- and R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0319] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is CF3O- and R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0320] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is FCH2CFHCH2O- and R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0321] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is CH2FCH2O-, and R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0322] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is CF3CH2O-, and R 2 is H and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0323] In one embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 is alkoxy, and R 2 C 1~6 alkyl, and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0324] In one embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 is alkoxy, and R 2 is CH3- and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0325] In one embodiment, the present invention provides a compound comprising R 1 is a haloC selected from CHF2O-, CH2FO-, CF3O-, FCH2CFHCH2O-, CH2FCH2O-, and CF3CH2O- 1~6 is alkoxy, and R 2 is CH3- and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0326] In one embodiment, the present invention provides a compound comprising R 1 is CHF2O- and R 2 is CH3- and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0327] In one embodiment, the present invention provides a compound comprising R 1 is CH2FO- and R 2 is CH3- and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0328] In one embodiment, the present invention provides a compound comprising R 1 is CF3O- and R 2 is CH3- and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0329] In one embodiment, the present invention provides a compound comprising R 1 is FCH2CFHCH2O- and R 2 is CH3- and R 3is H, or a solvate or pharmaceutically acceptable salt thereof.

[0330] In one embodiment, the present invention provides a compound comprising R 1 is CH2FCH2O-, and R 2 is CH3- and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0331] In one embodiment, the present invention provides a compound comprising R 1 is CF3CH2O-, and R 2 is CH3- and R 3 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0332] In one embodiment, the present invention provides a method for producing a compound comprising: (i) R 4 and R 5 one of which is H and the other is halogen, or (ii) R 4 and R 5 are both H, or (iii) R 4 and R 5 is halogen, or a solvate or pharmaceutically acceptable salt thereof.

[0333] In one embodiment, the present invention provides a compound comprising R 4 and R 5 are both H or both are halogen, or a solvate or pharmaceutically acceptable salt thereof.

[0334] In one preferred embodiment, the present invention provides a compound comprising R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0335] In one embodiment, the present invention provides a compound comprising R 4 and R 5and R are both halogen, or a solvate or pharmaceutically acceptable salt thereof.

[0336] In one embodiment, the present invention provides a compound comprising R 4 and R 5 are halogens selected from F- and Cl-, or a solvate or pharmaceutically acceptable salt thereof.

[0337] In one embodiment, the present invention provides a compound comprising R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0338] In one embodiment, the present invention provides a compound comprising R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0339] In one preferred embodiment, the present invention provides a compound comprising R 1 But, Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with one, two, or three substituents independently selected from alkoxy; 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0340] In one preferred embodiment, the present invention provides a compound comprising R 1 is cyano and R 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0341] In one preferred embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 alkyl, and R 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0342] In one preferred embodiment, the present invention provides a compound comprising R 1 is a halogen as described herein, and R 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0343] In one preferred embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 a 5-membered heteroaryl as described herein optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0344] In one preferred embodiment, the present invention provides a compound comprising R1 C as described herein 1~6 alkyl, and R 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0345] In one preferred embodiment, the present invention provides a compound comprising R 1 C as described herein 1~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0346] In one preferred embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 3- to 6-membered cycloalkylC optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy 0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0347] In one preferred embodiment, the present invention provides a compound comprising R 1 is unsubstituted 3- to 6-membered cycloalkyl C 0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0348] In one preferred embodiment, the present invention provides a compound comprising R1 But halogen, halo C 1~6 Alkyl and haloC 1~6 R is a 4- to 6-membered heterocycloalkyl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0349] In one preferred embodiment, the present invention provides a compound comprising R 1 is an unsubstituted 4- to 6-membered heterocycloalkyl, and R 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0350] In one preferred embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 4- to 6-membered heterocycloalkyl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; 0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0351] In one embodiment, the present invention provides a compound comprising R 1 is unsubstituted 4-6 membered heterocycloalkyl C 0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0352] In one preferred embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 phenoxy optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0353] In one preferred embodiment, the present invention provides a compound comprising R 1 is unsubstituted phenoxy, and R 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0354] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0355] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is a haloC selected from CHF2O-, CH2FO-, CF3O-, FCH2CFHCH2O-, CH2FCH2O-, and CF3CH2O- 1~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0356] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 HaloC is CHF2O- 1~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0357] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is CH2FO- and R 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0358] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is CF3O- and R 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0359] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is FCH2CFHCH2O- and R 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0360] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is CH2FCH2O-, and R 2is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0361] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 is CF3CH2O-, and R 2 is H and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0362] In one embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 is alkoxy, and R 2 C 1~6 alkyl, and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0363] In one embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 is alkoxy, and R 2 is CH3- and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0364] In one embodiment, the present invention provides a compound comprising R 1 is a haloC selected from CHF2O-, CH2FO-, CF3O-, FCH2CFHCH2O-, CH2FCH2O-, and CF3CH2O- 1~6 is alkoxy, and R 2 is CH3- and R 3 is H and R 4 and R 5are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0365] In one embodiment, the present invention provides a compound comprising R 1 is CHF2O- and R 2 is CH3- and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0366] In one embodiment, the present invention provides a compound comprising R 1 is CH2FO- and R 2 is CH3- and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0367] In one embodiment, the present invention provides a compound comprising R 1 is CF3O- and R 2 is CH3- and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0368] In one embodiment, the present invention provides a compound comprising R 1 is FCH2CFHCH2O- and R 2 is CH3- and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0369] In one embodiment, the present invention provides a compound comprising R 1 is CH2FCH2O-, and R 2 is CH3- and R 3 is H and R 4 and R 5are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0370] In one embodiment, the present invention provides a compound comprising R 1 is CF3CH2O-, and R 2 is CH3- and R 3 is H and R 4 and R 5 are both H, or a solvate or pharmaceutically acceptable salt thereof.

[0371] In one embodiment, the present invention provides a compound comprising R 1 But, Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with one, two, or three substituents independently selected from alkoxy; 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0372] In one embodiment, the present invention provides a compound comprising R 1 is cyano and R 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0373] In one embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 alkyl, and R 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0374] In one embodiment, the present invention provides a compound comprising R 1 is a halogen as described herein, and R 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0375] In one embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 a 5-membered heteroaryl as described herein optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0376] In one embodiment, the present invention provides a compound comprising R 1 C as described herein 1~6 alkyl, and R 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0377] In one embodiment, the present invention provides a compound comprising R 1 C as described herein1~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0378] In one embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 3- to 6-membered cycloalkylC optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy 0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0379] In one embodiment, the present invention provides a compound comprising R 1 is unsubstituted 3- to 6-membered cycloalkyl C 0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0380] In one embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 R is a 4- to 6-membered heterocycloalkyl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0381] In one embodiment, the present invention provides a compound comprising R 1 is an unsubstituted 4- to 6-membered heterocycloalkyl, and R 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0382] In one embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 4- to 6-membered heterocycloalkyl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; 0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0383] In one embodiment, the present invention provides a compound comprising R 1 is unsubstituted 4-6 membered heterocycloalkyl C 0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0384] In one embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 phenoxy optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 2 is H and R 3 is H and R 4 and R 5and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0385] In one embodiment, the present invention provides a compound comprising R 1 is unsubstituted phenoxy, and R 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0386] In one embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0387] In one embodiment, the present invention provides a compound comprising R 1 is a haloC selected from CHF2O-, CH2FO-, CF3O-, FCH2CFHCH2O-, CH2FCH2O-, and CF3CH2O- 1~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0388] In one embodiment, the present invention provides a compound comprising R 1 is CHF2O- and R 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0389] In one embodiment, the present invention provides a compound comprising R1 is CH2FO- and R 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0390] In one embodiment, the present invention provides a compound comprising R 1 is CF3O- and R 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0391] In one embodiment, the present invention provides a compound comprising R 1 is FCH2CFHCH2O- and R 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0392] In one embodiment, the present invention provides a compound comprising R 1 is CH2FCH2O-, and R 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0393] In one embodiment, the present invention provides a compound comprising R 1 is CF3CH2O-, and R 2 is H and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0394] In one embodiment, the present invention provides a compound comprising R1 is a haloC as described herein 1~6 is alkoxy, and R 2 C 1~6 alkyl, and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0395] In one embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 is alkoxy, and R 2 is CH3- and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0396] In one embodiment, the present invention provides a compound comprising R 1 is a haloC selected from CHF2O-, CH2FO-, CF3O-, FCH2CFHCH2O-, CH2FCH2O-, and CF3CH2O- 1~6 is alkoxy, and R 2 is CH3- and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0397] In one embodiment, the present invention provides a compound comprising R 1 is CHF2O- and R 2 is CH3- and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0398] In one embodiment, the present invention provides a compound comprising R 1 is CH2FO- and R 2 is CH3- and R 3is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0399] In one embodiment, the present invention provides a compound comprising R 1 is CF3O- and R 2 is CH3- and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0400] In one embodiment, the present invention provides a compound comprising R 1 is FCH2CFHCH2O- and R 2 is CH3- and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0401] In one embodiment, the present invention provides a compound comprising R 1 is CH2FCH2O-, and R 2 is CH3- and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0402] In one embodiment, the present invention provides a compound comprising R 1 is CF3CH2O-, and R 2 is CH3- and R 3 is H and R 4 and R 5 and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and R are each independently 0 or 1; and

[0403] In one embodiment, the present invention provides a compound comprising R 1 But, Cyano, Halo C 1~6Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with one, two, or three substituents independently selected from alkoxy; 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0404] In one embodiment, the present invention provides a compound comprising R 1 is cyano and R 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0405] In one embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 alkyl, and R 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0406] In one embodiment, the present invention provides a compound comprising R 1 is a halogen as described herein, and R 2 is H and R 3 is H and R 4 is H and R5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0407] In one embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 5-membered heteroaryl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0408] In one embodiment, the present invention provides a compound comprising R 1 C as described herein 1~6 alkyl, and R 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0409] In one embodiment, the present invention provides a compound comprising R 1 C as described herein 1~6 is alkoxy, and R 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0410] In one embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 3- to 6-membered cycloalkylC optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy 0~6 is alkoxy, and R 2 is H and R3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0411] In one embodiment, the present invention provides a compound comprising R 1 is unsubstituted 3- to 6-membered cycloalkyl C 0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0412] In one embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 R is a 4- to 6-membered heterocycloalkyl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0413] In one embodiment, the present invention provides a compound comprising R 1 is an unsubstituted 4- to 6-membered heterocycloalkyl, and R 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0414] In one embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 4- to 6-membered heterocycloalkyl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy;0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0415] In one embodiment, the present invention provides a compound comprising R 1 is unsubstituted 4-6 membered heterocycloalkyl C 0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0416] In one embodiment, the present invention provides a compound comprising R 1 But halogen, halo C 1~6 Alkyl and haloC 1~6 phenoxy optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0417] In one embodiment, the present invention provides a compound comprising R 1 is unsubstituted phenoxy, and R 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0418] In one embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 is alkoxy, and R 2 is H and R 3 is H and R4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0419] In one embodiment, the present invention provides a compound comprising R 1 is a haloC selected from CHF2O-, CH2FO-, CF3O-, FCH2CFHCH2O-, CH2FCH2O-, and CF3CH2O- 1~6 is alkoxy, and R 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0420] In one embodiment, the present invention provides a compound comprising R 1 is CHF2O- and R 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0421] In one embodiment, the present invention provides a compound comprising R 1 is CH2FO- and R 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0422] In one embodiment, the present invention provides a compound comprising R 1 is CF3O- and R 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0423] In one embodiment, the present invention provides a compound comprising R1 is FCH2CFHCH2O- and R 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0424] In one embodiment, the present invention provides a compound comprising R 1 is CH2FCH2O-, and R 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0425] In one embodiment, the present invention provides a compound comprising R 1 is CF3CH2O-, and R 2 is H and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0426] In one embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 is alkoxy, and R 2 C 1~6 alkyl, and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0427] In one embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 is alkoxy, and R 2 is CH3- and R 3 is H and R 4 is H and R 5is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0428] In one embodiment, the present invention provides a compound comprising R 1 is a haloC selected from CHF2O-, CH2FO-, CF3O-, FCH2CFHCH2O-, CH2FCH2O-, and CF3CH2O- 1~6 is alkoxy, and R 2 is CH3- and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0429] In one embodiment, the present invention provides a compound comprising R 1 is CHF2O- and R 2 is CH3- and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0430] In one embodiment, the present invention provides a compound comprising R 1 is CH2FO- and R 2 is CH3- and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0431] In one embodiment, the present invention provides a compound comprising R 1 is CF3O- and R 2 is CH3- and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0432] In one embodiment, the present invention provides a compound comprising R 1is FCH2CFHCH2O- and R 2 is CH3- and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0433] In one embodiment, the present invention provides a compound comprising R 1 is CH2FCH2O-, and R 2 is CH3- and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0434] In one embodiment, the present invention provides a compound comprising R 1 is CF3CH2O-, and R 2 is CH3- and R 3 is H and R 4 is H and R 5 is F-, or a solvate or pharmaceutically acceptable salt thereof.

[0435] In one preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 , R 6 and R 7 are as described herein), or a solvate or pharmaceutically acceptable salt thereof.

[0436] In one particularly preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 , R 6 and R7 are as described herein), or a solvate or pharmaceutically acceptable salt thereof.

[0437] In one particularly preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 , R 6 and R 7 are as described herein), or a solvate or pharmaceutically acceptable salt thereof.

[0438] In one embodiment, the present invention provides a compound comprising R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 Provided are compounds of formula (I), or solvates or pharmaceutically acceptable salts thereof, optionally substituted with one, two, or three substituents independently selected from alkoxy.

[0439] In one preferred embodiment, the present invention provides a compound comprising R 6 is phenyl optionally substituted as described herein, or a solvate or pharmaceutically acceptable salt thereof.

[0440] In one preferred embodiment, the present invention provides a compound comprising R 6 is unsubstituted phenyl, or a solvate or pharmaceutically acceptable salt thereof.

[0441] In one preferred embodiment, the present invention provides a compound comprising R 6is a saturated monocyclic 3- to 6-membered saturated monocyclic cycloalkyl optionally substituted as described herein, or a solvate or pharmaceutically acceptable salt thereof.

[0442] In one preferred embodiment, the present invention provides a compound comprising R 6 is a saturated monocyclic 3- to 6-membered cycloalkyl selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, optionally substituted as described herein, or a solvate or pharmaceutically acceptable salt thereof.

[0443] In one more preferred embodiment, the present invention provides a compound comprising R 6 is a saturated monocyclic 3- to 6-membered cycloalkyl selected from unsubstituted cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, or a solvate or pharmaceutically acceptable salt thereof.

[0444] In one more preferred embodiment, the present invention provides a compound comprising R 6 is unsubstituted cyclohexyl, or a solvate or pharmaceutically acceptable salt thereof.

[0445] In one embodiment, the present invention provides a compound comprising R 6 C 1~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0446] In one embodiment, the present invention provides a compound comprising R 6 is selected from CH3-, CH3CH2-, CH3CH2CH2-, (CH3)2CH2-, (CH3CH2CH2CH2-), (CH3)2CH2CH2-, CH3CH(CH3)CH2-, and (CH3)3C- 1~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0447] In one embodiment, the present invention provides a compound comprising R 6 is CH3-, or a solvate or pharmaceutically acceptable salt thereof.

[0448] In one embodiment, the present invention provides a compound comprising R 6 is a 4- to 6-membered heterocycloalkyl, or a solvate or pharmaceutically acceptable salt thereof.

[0449] In one embodiment, the present invention provides a compound comprising R 6 But halogen, halo C 1~6 Alkyl and haloC 1~6 Provided are compounds of formula (I), or solvates or pharmaceutically acceptable salts thereof, which are 4-6 membered heterocycloalkyl as described herein, optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy.

[0450] In one embodiment, the present invention provides a compound comprising R 6 is an unsubstituted 4-6 membered heterocycloalkyl as described herein, or a solvate or pharmaceutically acceptable salt thereof.

[0451] In one embodiment, the present invention provides a compound comprising R 6 is a 4- to 6-membered heterocycloalkyl selected from the following: [ka] or a solvate or pharmaceutically acceptable salt thereof.

[0452] In one embodiment, the present invention provides a compound comprising R 6 but [ka] or a solvate or pharmaceutically acceptable salt thereof. In one embodiment, the present invention provides a compound comprising R6 but

[0453] [ka] or a solvate or pharmaceutically acceptable salt thereof.

[0454] In one embodiment, the present invention provides a compound comprising R 6 but [ka] or a solvate or pharmaceutically acceptable salt thereof.

[0455] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 Halo C 1~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0456] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is a haloC selected from (CH3)2FC-, CF3CH2-, CH3CF2-, CF3-, CH2F-, and CHF2- 1~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0457] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3-, or a solvate or pharmaceutically acceptable salt thereof.

[0458] In one preferred embodiment, the present invention provides a compound comprising R 6 is (CH3)2FC-, or a solvate or pharmaceutically acceptable salt thereof.

[0459] In one preferred embodiment, the present invention provides a compound comprising R 6is CF3CH2-, or a solvate or pharmaceutically acceptable salt thereof.

[0460] In one preferred embodiment, the present invention provides a compound comprising R 6 is CH3CF2-, or a solvate or pharmaceutically acceptable salt thereof.

[0461] In one preferred embodiment, the present invention provides a compound comprising R 6 is CH2F-, or a solvate or pharmaceutically acceptable salt thereof.

[0462] In one preferred embodiment, the present invention provides a compound comprising R 6 is CH3CF2-, or a solvate or pharmaceutically acceptable salt thereof.

[0463] In one preferred embodiment, the present invention provides a compound comprising R 6 is CH3CF2-, having a structure selected from the following, or a solvate or pharmaceutically acceptable salt thereof: [ka]

[0464] In one preferred embodiment, the present invention provides a compound comprising R 6 is CH3CF2-, having the following structure: [ka]

[0465] In one preferred embodiment, the present invention provides a compound comprising R 6 is CH3CF2-, having the following structure: [ka]

[0466] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3- selected from the following structures, or a solvate or pharmaceutically acceptable salt thereof: [ka]

[0467] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3-, having the following structure: [ka]

[0468] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3-, having the following structure: [ka]

[0469] In one preferred embodiment, the present invention provides a compound comprising R 1 But, Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6optionally substituted with one, two, or three substituents independently selected from alkoxy; 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is phenyl, as described herein, or a solvate or pharmaceutically acceptable salt thereof.

[0470] In one more preferred embodiment, the present invention provides a compound comprising R 1 But, Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with one, two, or three substituents independently selected from alkoxy; 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is phenyl, as described herein, or a solvate or pharmaceutically acceptable salt thereof.

[0471] In one more preferred embodiment, the present invention provides a compound comprising R 1 But, Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with one, two, or three substituents independently selected from alkoxy; 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is a saturated monocyclic 3- to 6-membered cycloalkyl as described herein, or a solvate or pharmaceutically acceptable salt thereof.

[0472] In one preferred embodiment, the present invention provides a compound comprising R 1 But, Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with one, two, or three substituents independently selected from alkoxy; 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 C as described herein 1~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0473] In one preferred embodiment, the present invention provides a compound comprising R 1 But, Cyano, Halo C1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with one, two, or three substituents independently selected from alkoxy; 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is a 4- to 6-membered heterocycloalkyl as described herein, or a solvate or pharmaceutically acceptable salt thereof.

[0474] In one particularly preferred embodiment, the present invention provides a compound comprising R 1 But, Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with one, two, or three substituents independently selected from alkoxy; 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6is a haloC as described herein 1~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0475] In one preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0476] In one particularly preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0477] In one particularly preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0478] In one preferred embodiment, the present invention provides a compound comprising R 7 is H or C 1~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0479] In one more preferred embodiment, the present invention provides a compound comprising R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0480] In one preferred embodiment, the present invention provides a compound comprising R 7 C 1~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0481] In one preferred embodiment, the present invention provides a compound comprising R 7 is selected from CH3-, CH3CH2-, CH3CH2CH2-, (CH3)2CH2-, (CH3CH2CH2CH2-), (CH3)2CH2CH2-, CH3CH(CH3)CH2-, and (CH3)3C- 1~6 The present invention provides a compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0482] In one preferred embodiment, the present invention provides a compound comprising R 7 is CH3-, or a solvate or pharmaceutically acceptable salt thereof.

[0483] In one preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0484] In one preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6 phenyl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H and C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0485] In one more preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6 phenyl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H), or a solvate or pharmaceutically acceptable salt thereof.

[0486] In one preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6 phenyl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0487] In one more preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6 saturated monocyclic 3- to 6-membered cycloalkyl as described herein optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0488] In one more preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6saturated monocyclic 3- to 6-membered cycloalkyl as described herein optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H and C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0489] In one more preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6 saturated monocyclic 3- to 6-membered cycloalkyl as described herein optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H), or a solvate or pharmaceutically acceptable salt thereof.

[0490] In one more preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 alkoxy, 3- to 6-membered cycloalkylalkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC0-6alkoxy, and phenoxy; heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6 saturated monocyclic 3- to 6-membered cycloalkyl as described herein optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0491] In one preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is C 1~6 is alkyl, R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0492] In one preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is C 1~6 is alkyl, R 7 is H and C1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0493] In one preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is C 1~6 is alkyl, R 7 is H), or a solvate or pharmaceutically acceptable salt thereof.

[0494] In one preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is C 1~6 is alkyl, R 7 is C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0495] In one preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a 4-6 membered heterocycloalkyl as described herein; R 7 is H, C1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0496] In one preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a 4-6 membered heterocycloalkyl as described herein; R 7 is H and C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0497] In one preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a 4-6 membered heterocycloalkyl as described herein; R 7 is H), or a solvate or pharmaceutically acceptable salt thereof.

[0498] In one preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6is a 4-6 membered heterocycloalkyl as described herein; R 7 is C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0499] In one preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a haloC as described herein 1~6 is alkyl, R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0500] In one more preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a haloC as described herein 1~6 is alkyl, R 7 is H and C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0501] In one more preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a haloC as described herein 1~6 is alkyl, R 7 is H), or a solvate or pharmaceutically acceptable salt thereof.

[0502] In one more preferred embodiment, the present invention provides a compound of formula (III) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a haloC as described herein 1~6 is alkyl, R 7 is C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0503] In one preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0504] In one preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6 phenyl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H and C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0505] In one preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6 phenyl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H), or a solvate or pharmaceutically acceptable salt thereof.

[0506] In one preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6 phenyl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0507] In one preferred embodiment, the present invention provides a compound of formula (IV): [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6 saturated monocyclic 3- to 6-membered cycloalkyl as described herein optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0508] In one preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6 saturated monocyclic 3- to 6-membered cycloalkyl as described herein optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H and C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0509] In one preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6 saturated monocyclic 3- to 6-membered cycloalkyl as described herein optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H), or a solvate or pharmaceutically acceptable salt thereof.

[0510] In one preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6saturated monocyclic 3- to 6-membered cycloalkyl as described herein optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0511] In one preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is C 1~6 is alkyl, R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0512] In one preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is C 1~6 is alkyl, R 7 is H and C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0513] In one preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is C 1~6 is alkyl, R 7 is H), or a solvate or pharmaceutically acceptable salt thereof.

[0514] In one preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is C 1~6 is alkyl, R 7 is C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0515] In one preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a 4-6 membered heterocycloalkyl as described herein; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0516] In one preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a 4-6 membered heterocycloalkyl as described herein; R 7 is H and C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0517] In one preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a 4-6 membered heterocycloalkyl as described herein; R 7 is H), or a solvate or pharmaceutically acceptable salt thereof.

[0518] In one preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a 4-6 membered heterocycloalkyl as described herein; R 7 is C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0519] In one preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a haloC as described herein 1~6 is alkyl, R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0520] In one preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a haloC as described herein 1~6 is alkyl, R 7 is H and C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0521] In one particularly preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a haloC as described herein 1~6 is alkyl, R 7 is H), or a solvate or pharmaceutically acceptable salt thereof.

[0522] In one particularly preferred embodiment, the present invention provides a compound of formula (IV) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a haloC as described herein 1~6 is alkyl, R 7 is C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0523] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0524] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6 phenyl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H and C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0525] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6 phenyl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H), or a solvate or pharmaceutically acceptable salt thereof.

[0526] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6 phenyl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0527] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6Alkyl and haloC 1~6 saturated monocyclic 3- to 6-membered cycloalkyl as described herein optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0528] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6 saturated monocyclic 3- to 6-membered cycloalkyl as described herein optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H and C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0529] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6 saturated monocyclic 3- to 6-membered cycloalkyl as described herein optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H), or a solvate or pharmaceutically acceptable salt thereof.

[0530] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is halogen, halo C 1~6 Alkyl and haloC 1~6 saturated monocyclic 3- to 6-membered cycloalkyl as described herein optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0531] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is C 1~6 is alkyl, R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0532] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is C 1~6 is alkyl, R 7 is H and C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0533] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is C 1~6 is alkyl, R 7 is H), or a solvate or pharmaceutically acceptable salt thereof.

[0534] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is C 1~6 is alkyl, R 7 is C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0535] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy; heteroaryl, heterocycloalkyl, Heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is not a halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a 4-6 membered heterocycloalkyl as described herein; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0536] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a 4-6 membered heterocycloalkyl as described herein; R 7 is H and C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0537] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a 4-6 membered heterocycloalkyl as described herein; R 7 is H), or a solvate or pharmaceutically acceptable salt thereof.

[0538] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a 4-6 membered heterocycloalkyl as described herein; R 7 is C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0539] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a haloC as described herein 1~6 is alkyl, R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0540] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a haloC as described herein 1~6 is alkyl, R 7 is H and C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0541] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a haloC as described herein 1~6 is alkyl, R 7 is H), or a solvate or pharmaceutically acceptable salt thereof.

[0542] In one preferred embodiment, the present invention provides a compound of formula (V) [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is a haloC as described herein 1~6 is alkyl, R 7 is C 1~6 alkyl), or a solvate or pharmaceutically acceptable salt thereof.

[0543] In one preferred embodiment, the present invention provides a compound comprising R 1 are cyano, halogen, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 5-membered heteroaryl, 4-6-membered heterocycloalkylC 0~6 Alkoxy, HaloC 1~6 Alkyl, 3-6 membered cycloalkylC 0~6 alkoxy, and phenoxy, and R 2 is H and R 3 is H and R 4and R 5 Both are H and R 6 is unsubstituted phenyl, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0544] In one preferred embodiment, the present invention provides a compound comprising R 1 is cyano and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is unsubstituted phenyl, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0545] In one preferred embodiment, the present invention provides a compound comprising R 1 is a halogen as described herein, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is unsubstituted phenyl, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0546] In one preferred embodiment, the present invention provides a compound comprising R 1 C as described herein 1~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is unsubstituted phenyl, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0547] In one more preferred embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 is alkoxy, and R2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is unsubstituted phenyl, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0548] In one preferred embodiment, the present invention provides a compound comprising R 1 is a 5-membered heteroaryl as described herein, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is unsubstituted phenyl, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0549] In one preferred embodiment, the present invention provides a compound comprising R 1 is a 4- to 6-membered heterocycloalkyl C 0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is unsubstituted phenyl, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0550] In one preferred embodiment, the present invention provides a compound comprising R 1 is a 3- to 6-membered cycloalkyl C 0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is unsubstituted phenyl, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0551] In one preferred embodiment, the present invention provides a compound comprising R 1 is phenoxy as described herein, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is unsubstituted phenyl, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0552] In one preferred embodiment, the present invention provides a compound comprising R 1 are cyano, halogen, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 5-membered heteroaryl, 4-6-membered heterocycloalkylC 0~6 Alkoxy, HaloC 1~6 Alkyl, 3-6 membered cycloalkylC 0~6 alkoxy, and phenoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl as described herein, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0553] In one preferred embodiment, the present invention provides a compound comprising R 1 is cyano and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl as described herein, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0554] In one preferred embodiment, the present invention provides a compound comprising R 1 is a halogen as described herein, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl as described herein, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0555] In one preferred embodiment, the present invention provides a compound comprising R 1 C as described herein 1~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl as described herein, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0556] In one preferred embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl as described herein, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0557] In one preferred embodiment, the present invention provides a compound comprising R 1 is a 5-membered heteroaryl as described herein, and R 2 is H and R 3 is H and R 4 and R 5Both are H and R 6 is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl as described herein, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0558] In one preferred embodiment, the present invention provides a compound comprising R 1 is a 4- to 6-membered heterocycloalkyl C 0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl as described herein, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0559] In one preferred embodiment, the present invention provides a compound comprising R 1 is a 3- to 6-membered cycloalkyl C 0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl as described herein, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0560] In one preferred embodiment, the present invention provides a compound comprising R 1 is phenoxy as described herein, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl as described herein, and R 7is H, or a solvate or pharmaceutically acceptable salt thereof.

[0561] In one embodiment, the present invention provides a compound comprising R 1 are cyano, halogen, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 5-membered heteroaryl, 4-6-membered heterocycloalkylC 0~6 Alkoxy, HaloC 1~6 Alkyl, 3-6 membered cycloalkylC 0~6 alkoxy, and phenoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl as described herein; R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0562] In one preferred embodiment, the present invention provides a compound comprising R 1 is cyano and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl as described herein; R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0563] In one embodiment, the present invention provides a compound comprising R 1 is a halogen as described herein, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl as described herein; R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0564] In one embodiment, the present invention provides a compound comprising R 1 C as described herein 1~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl as described herein; R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0565] In one more preferred embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl as described herein; R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0566] In one preferred embodiment, the present invention provides a compound comprising R 1 is a 5-membered heteroaryl as described herein, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl as described herein; R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0567] In one embodiment, the present invention provides a compound comprising R 1 is a 4- to 6-membered heterocycloalkyl C 0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl as described herein; R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0568] In one preferred embodiment, the present invention provides a compound comprising R 1 is a 3- to 6-membered cycloalkyl C 0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl as described herein; R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0569] In one embodiment, the present invention provides a compound comprising R 1 is phenoxy as described herein, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl as described herein; R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0570] In some embodiments described herein, the unsubstituted saturated monocyclic 3-6 membered cycloalkyl is unsubstituted cyclohexyl.

[0571] In one preferred embodiment, the present invention provides a compound comprising R 1 are cyano, halogen, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 5-membered heteroaryl, 4-6-membered heterocycloalkylC 0~6 Alkoxy, HaloC 1~6 Alkyl, 3-6 membered cycloalkylC 0~6 alkoxy, and phenoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is a haloC as described herein 1~6 alkyl, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0572] In one preferred embodiment, the present invention provides a compound comprising R 1 is cyano and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is a haloC as described herein 1~6 alkyl, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0573] In one preferred embodiment, the present invention provides a compound comprising R 1is a halogen as described herein, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is a haloC as described herein 1~6 alkyl, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0574] In one more preferred embodiment, the present invention provides a compound comprising R 1 C as described herein 1~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is a haloC as described herein 1~6 alkyl, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0575] In one more preferred embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is a haloC as described herein 1~6 alkyl, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0576] In one more preferred embodiment, the present invention provides a compound comprising R 1 is a 5-membered heteroaryl as described herein, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6is a haloC as described herein 1~6 alkyl, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0577] In one more preferred embodiment, the present invention provides a compound comprising R 1 is a 4- to 6-membered heterocycloalkyl C 0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is a haloC as described herein 1~6 alkyl, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0578] In one more preferred embodiment, the present invention provides a compound comprising R 1 is a 3- to 6-membered cycloalkylalkoxy as described herein, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is a haloC as described herein 1~6 alkyl, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0579] In one more preferred embodiment, the present invention provides a compound comprising R 1 is phenoxy as described herein, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is a haloC as described herein 1~6 alkyl, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0580] In some of the above embodiments, R 6 is a haloC selected from (CH3)2FC-, CF3CH2-, CH3CF2-, CF3-, CH2F-, and CHF2- 1~6 It is alkyl.

[0581] In one preferred embodiment, the present invention provides a compound comprising R 6 is CH3CF2-, or a solvate or pharmaceutically acceptable salt thereof.

[0582] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CH3CF2-, having a structure selected from the following, or a solvate or pharmaceutically acceptable salt thereof: [ka]

[0583] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CH3CF2-, having the following structure: [ka]

[0584] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CH3CF2-, having the following structure: [ka]

[0585] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3-, or a solvate or pharmaceutically acceptable salt thereof.

[0586] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3-, having the following structure: [ka]

[0587] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3-, having the following structure: [ka]

[0588] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3-, having the following structure: [ka]

[0589] In one embodiment, the present invention provides a compound comprising R 1 are cyano, halogen, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 5-membered heteroaryl, 4-6-membered heterocycloalkylC 0~6 Alkoxy, HaloC 1~6 Alkyl, 3-6 membered cycloalkylC 0~6 alkoxy, and phenoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is a haloC as described herein 1~6 is alkoxy, and R 7is H, or a solvate or pharmaceutically acceptable salt thereof.

[0590] In one preferred embodiment, the present invention provides a compound comprising R 1 is cyano and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is a haloC as described herein 1~6 is alkoxy, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0591] In one embodiment, the present invention provides a compound comprising R 1 is a halogen as described herein, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is a haloC as described herein 1~6 is alkoxy, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0592] In one embodiment, the present invention provides a compound comprising R 1 C as described herein 1~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is a haloC as described herein 1~6 is alkoxy, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0593] In one preferred embodiment, the present invention provides a compound comprising R 1 is a haloC as described herein 1~6 is alkoxy, and R 2is H and R 3 is H and R 4 and R 5 Both are H and R 6 is a haloC as described herein 1~6 is alkoxy, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0594] In one preferred embodiment, the present invention provides a compound comprising R 1 is a 5-membered heteroaryl as described herein, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is a haloC as described herein 1~6 is alkoxy, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0595] In one embodiment, the present invention provides a compound comprising R 1 is a 4- to 6-membered heterocycloalkyl C 0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is a haloC as described herein 1~6 is alkoxy, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0596] In one preferred embodiment, the present invention provides a compound comprising R 1 is a 3- to 6-membered cycloalkyl C 0~6 is alkoxy, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is a haloC as described herein 1~6alkyl, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0597] In one embodiment, the present invention provides a compound comprising R 1 is phenoxy as described herein, and R 2 is H and R 3 is H and R 4 and R 5 Both are H and R 6 is a haloC as described herein 1~6 is alkoxy, and R 7 is H, or a solvate or pharmaceutically acceptable salt thereof.

[0598] In some of the above embodiments, R 6 is CHF2O-, and haloC selected from CH2FO-, CF3O-, FCH2CFHCH2O-, CH2FCH2O-, and CF3CH2O- 1~6 It is an alkoxy.

[0599] In one more preferred embodiment, the present invention provides a compound of formula (VI) [ka] (In the formula, R 1 and R 6 are as described herein), or a solvate or pharmaceutically acceptable salt thereof.

[0600] In one more preferred embodiment, the present invention provides a compound of formula (VII) [ka] (In the formula, R 1 and R 6 are as described herein), or a solvate or pharmaceutically acceptable salt thereof.

[0601] In one more preferred embodiment, the present invention provides a compound of formula (VIII) [ka] (In the formula, R 1 and R 6 are as described herein), or a solvate or pharmaceutically acceptable salt thereof.

[0602] Exemplary compounds of formula (I) in Table 1 were used to inhibit Kv7.2 (EC 50 It was prepared, characterized, and tested for <10 micromolar (μM) and % maximum activation of Kv7.2 activation and has the following structure and corresponding name (OpenEye Lexichem, version 1.2.0, OpenEye Scientific Software, Santa Fe, NM, USA; https: / / www.eyesopen.com / lexichem-tk).

[0603] In some embodiments, the compound is selected from Table 1, or a solvate or pharmaceutically acceptable salt thereof. [Table 1] TIFF2025502712000122.tif235170 TIFF2025502712000123.tif240170 TIFF2025502712000124.tif227170 TIFF2025502712000125.tif231170 TIFF2025502712000126.tif242170 TIFF2025502712000127.tif236170 TIFF2025502712000128.tif86170

[0604] The compounds of the present invention have been shown to be agents acting on Kv7.2 and are therefore useful for the treatment and / or prevention of any of the diseases, disorders, or disability disorders described herein. They are particularly useful for the therapeutic and / or prophylactic treatment of Kv7.2-related disorders, diseases, or disability disorders. More particularly, they are useful for the therapeutic and / or prophylactic treatment of Kv7.2-related disorders, diseases, or disability disorders selected from behavioral disorders, mood disorders, neurodevelopmental disorders, intellectual disabilities, epilepsy, neurodegenerative diseases, pain, migraine, and tinnitus. Behavioral disorders include attention deficit hyperactivity disorder (ADHD). Mood disorders include depression. Neurodevelopmental disorders include autism spectrum disorders (ASD) or symptomatic developmental disorders. Symptomatic developmental disorders include Dup15q syndrome (Dup15q), fragile X syndrome (FXS), and Angelman syndrome. Epilepsy is, for example, widespread childhood epilepsy, West syndrome, Ohtahara syndrome and epileptic encephalopathy. Neurodegenerative diseases are, for example, Alzheimer's disease or motor neuron disease.

[0605] Thus, the compounds of the present invention are useful Kv7.2 modulators that offer favorable pharmacological properties such as potency, selectivity and metabolic stability.

[0606] Compounds having one or more of the following combinations of characteristics have particularly beneficial Kv7.2 EC values ​​in the following ranges: 50 These antibodies have been found to exhibit the following selectivity ratios: (i) EC 50 <3 μM, selectivity ratio >10-fold, or (ii) EC 50 <1 μM, selectivity ratio >30-fold.

[0607] Compounds of the present invention, particularly those having a human hepatic microsomal clearance rate of less than 20 μl / min / mg, have been found to exhibit beneficial metabolic stability.

[0608] In one more preferred embodiment of the invention, the compound of the invention has the formula [ka] (In the formula, A 1 and A 3 is N and A 2 is CH, or A 1 is N and A 2 and A 3 is CH, R 1 Halo C 1~6 is an alkoxy; R 2 is hydrogen, R 3 is hydrogen, R 4 and R 5 is hydrogen, R 6 Halo C 1~6 is alkyl, R 7 is hydrogen) It has.

[0609] In another more preferred embodiment of the present invention, the compound of the present invention has the formula [ka] (In the formula, A 1 and A 3 is N and A 2 is CH, or A 1 is N and A 2 and A 3 is CH, R 1 is a haloC selected from CHF2O-, CFH2O-, CF3O-, CHF2CH2O-, FCH2CFHCH2O-, and CF3CH2O- 1~6 is an alkoxy; R 2 is hydrogen, R 3 is hydrogen, R4 and R 5 is hydrogen, R 6 is a halo group selected from CF3-, CHF2-, CH3CF2-, and CFH2- 1~6 is alkyl, R 7 is hydrogen) It has.

[0610] In another more preferred embodiment of the present invention, the compound of the present invention has the formula [ka] (In the formula, A 1 and A 3 is N and A 2 is CH, or A 1 is N and A 2 and A 3 is CH, R 1 is a halo group selected from CHF2O- and CF3CH2O- 1~6 is an alkoxy; R 2 is hydrogen, R 3 is hydrogen, R 4 and R 5 is hydrogen, R 6 is a halo group selected from CF3 and CH3CF2- 1~6 is alkyl, R 7 is hydrogen) It has.

[0611] In one more preferred embodiment of the present invention, the compound of the present invention is of formula (IX) [ka] (In the formula, R 6is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); It has.

[0612] In one particularly preferred embodiment of the present invention, the compound of the present invention has the formula (X) [ka] (In the formula, R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, and haloC, all as described herein. 1~6 alkyl, and R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen) It has.

[0613] In some preferred embodiments where the compound has formula (X), R 6 is unsubstituted phenyl, and R 7 is H or C 1~6 It is alkyl.

[0614] In some preferred embodiments where the compound has formula (X), R 6 is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl, and R 7 is H or C 1~6 It is alkyl.

[0615] In some preferred embodiments where the compound has formula (X), R 6is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl; R 7 is H or C 1~6 It is alkyl.

[0616] In some preferred embodiments where the compound has formula (X), R 6 is a haloC selected from (CH3)2FC-, CF3CH2-, CH3CF2-, CF3-, CH2F-, and CHF2- 1~6 alkyl, and R 7 is H or C 1~6 It is alkyl.

[0617] In some preferred embodiments where the compound has formula (X), R 6 is CH3CF2- and R 7 is H or C 1~6 It is alkyl. In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CH3CF2- and has a structure selected from: [ka] R 7 is H or C 1~6 The present invention provides a compound of formula (X), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0618] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CH3CF2- and has the structure [ka]

[0619] R 7 is H or C 1~6 The present invention provides a compound of formula (X), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0620] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CH3CF2- and has the structure [ka] R 7 is H or C 1~6 The present invention provides a compound of formula (X), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0621] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3-, or a solvate or pharmaceutically acceptable salt thereof.

[0622] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3- and has the structure [ka] R 7 is H or C 1~6 The present invention provides a compound of formula (X), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0623] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3- and has the structure [ka]

[0624] R 7 is H or C 1~6 The present invention provides a compound of formula (X), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0625] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3- and has the structure [ka] R 7 is H or C 1~6 The present invention provides a compound of formula (X), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0626] In one preferred embodiment of the present invention, the compound of the present invention is of formula (XI) [ka] (In the formula, R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with one, two, or three substituents independently selected from alkoxy; 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen) It has.

[0627] In some preferred embodiments where the compound has formula (XI), R 6 is unsubstituted phenyl, and R 7 is H or C 1~6 It is alkyl.

[0628] In some preferred embodiments where the compound has formula (XI), R 6 is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl, and R 7 is H or C 1~6 It is alkyl.

[0629] In some preferred embodiments where the compound has formula (XI), R 6is an unsubstituted saturated monocyclic 3- to 6-membered cycloalkyl selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl; R 7 is H or C 1~6 It is alkyl.

[0630] In some preferred embodiments where the compound has formula (XI), R 6 is a haloC selected from (CH3)2FC-, CF3CH2-, CH3CF2-, CF3-, CH2F-, and CHF2- 1~6 alkyl and R7 is H or C 1~6 It is alkyl.

[0631] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3CH2- and R 7 is H or C 1~6 The present invention provides a compound of formula (XI), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0632] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3CH2- and has a structure selected from: [ka] R 7 is H or C 1~6 The present invention provides a compound of formula (XI), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0633] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3CH2- and has the structure [ka] R7 is H or C 1~6 The present invention provides a compound of formula (XI), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0634] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3CH2- and has the structure [ka] R 7 is H or C 1~6 The present invention provides a compound of formula (XI), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0635] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3- and R7 is H or C 1~6 The present invention provides a compound of formula (XI), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0636] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3- and has the structure [ka] R 7 is H or C 1~6 The present invention provides a compound of formula (XI), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0637] In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3- and has the structure [ka] R7 is H or C 1~6 The present invention provides a compound of formula (XI), or a solvate or pharmaceutically acceptable salt thereof, wherein: In one particularly preferred embodiment, the present invention provides a compound comprising R 6 is CF3- and has the structure [ka] R 7 is H or C 1~6 The present invention provides a compound of formula (XI), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0638] In some preferred embodiments, the compound of formula (I), or a solvate or pharmaceutically acceptable salt thereof, is selected from Table 2 (Kv7.2 EC 50 <3 μM and; selectivity (Kv7.5_7.3 / Kv7.2) >10-fold. [Table 2] TIFF2025502712000148.tif246161 TIFF2025502712000149.tif30161

[0639] Compounds of formula (I) or (I') having one or more of the following combinations of features have particularly beneficial Kv7.2 EC values ​​in the following ranges: 50 and / or Kv7.5_7.3 / Kv7.2 selectivity ratio: EC 50 <3 μM, selectivity ratio >10-fold, EC 50 <1 μM, selectivity ratio >30-fold or EC 50 <1 μM, selectivity ratio >30-fold, and favorable metabolic stability.

[0640] The measurement is carried out by measuring whether a compound of formula (I) or formula (I'), or a solvate or pharmaceutical salt thereof, has a Kv7.2 EC 50 <3 μM and a selectivity ratio of Kv7.5_7.3 / Kv7.2 >10-fold were shown to have the favorable pharmacological properties described herein.

[0641] Measurements have also shown that compounds of formula (I) or (I'), or solvates or pharmaceutical salts thereof, have the favorable pharmacological properties described herein and are therefore preferred if they exhibit one or more of the following properties: a Kv7.5_7.3 / Kv7.2 selectivity ratio of >10-fold, and / or a human hepatic microsomal clearance rate of <20 μl / min / mg, and / or Kv7.4 / Kv7.2 selectivity >10-fold

[0642] In some embodiments of the present invention, in the compounds of the present invention, one or more hydrogen atoms are replaced by deuterium.Surprisingly, it has been found that deuteration of the compounds of the present invention provides the advantage of maintaining the pharmacological profile of their hydrogen counterparts, while positively affecting their metabolic results.The selective replacement of one or more hydrogen atoms in the compounds of the present invention with deuterium improves the pharmaceutical profile of the compounds of the present invention, for example, by reducing the amount of undesired metabolites when compared with their all-hydrogen counterparts, and by reducing metabolic rate, thus increasing half-life.

[0643] The method of incorporating deuterium into a compound is well established.The compounds of the present invention can be tested using metabolic studies established in the art to identify the site for selective placement of deuterium isotopes that are not metabolized or are metabolized at a lower rate.Furthermore, these studies identify metabolic sites as the positions where deuterium atoms are placed.

[0644] In one embodiment, the present invention provides a compound of the present invention wherein one or more hydrogen atoms have been replaced with deuterium.

[0645] In one embodiment, the present invention provides a compound of the present invention, a compound of formula (I*) [ka] (In the formula, A 1is N or CH, A 2 is N or CH, A 3 is N or CH, provided that A 1 , A 2 , or A 3 at least one of is N, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 2 is H, D, or C 1~6 alkyl, R 3 is H or C 1~6 is alkyl, R 4 is H, D, or a halogen, R 5 is H, D, or a halogen, R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0646] In one preferred embodiment, the present invention provides a compound of the present invention, a compound of formula (II*) [ka] (In the formula, A 1 is N or CH, A 2 is N or CH, A 3 is N or CH, provided that A 1 , A 2 , or A 3 at least one of is N, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0647] In some preferred embodiments of compounds of formula (I*), R 2 is deuterium.

[0648] In some preferred embodiments of compounds of formula (I*) or (II*), R 1 is a haloC as described herein 1~6 is alkoxy, and R 2 is deuterium, and R 3 is H and R 4 and R 5 is H and R 6 phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, and haloC 1~6 alkyl, and R 7 is H or C 1~6 It is alkyl.

[0649] In some preferred embodiments of compounds of formula (II*), R 1 is a haloC as described herein 1~6 alkoxy, and R6 are phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, and haloC 1~6 alkyl, and R 7 is H or C 1~6 It is alkyl.

[0650] In some more preferred embodiments of compounds of formula (II*), R 1 is a haloC as described herein 1~6 is alkoxy, and R 6 all of which are described herein. 1~6 alkyl, and R 7 is H.

[0651] In one embodiment, the present invention provides a compound comprising R 2 H, D, and C 1~6 alkyl, and R 8 H, D, and C 1~6 The present invention provides a compound of formula (I'), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0652] In one embodiment, the present invention provides a compound comprising R 2 is H or D, and R 8 is H or D, or a solvate or pharmaceutically acceptable salt thereof.

[0653] In one embodiment, the present invention provides a compound comprising R 2 or R 8 is selected from CH3-, CH3CH2-, CH3CH2CH2-, (CH3)2CH2-, (CH3CH2CH2CH2-), (CH3)2CH2CH2-, CH3CH(CH3)CH2-, and (CH3)3C- 1~6 The present invention provides a compound of formula (I'), or a solvate or pharmaceutically acceptable salt thereof, wherein:

[0654] In one embodiment, the present invention provides a compound comprising R 2 or R 8 is D, or a solvate or pharmaceutically acceptable salt thereof.

[0655] Additional options for variables In all aspects, embodiments, claims and formulas described herein, the variable R 1 and R 2 In additional different aspects, embodiments and formulas, R 1 and R 2These lists of options for may each be independently expanded to include additional options from one or more of the lists associated with a given aspect, embodiment, or formula provided below. These additional options may be included independently of additional options for other variables in the formula, e.g., R 1 Additional options for a variable, such as may be independently included in a given formula without the need to include additional options for any of the other variables in the molecule, and similarly for each and every other variable.

[0656] Throughout this specification, this refers to one or more variables R 1 and R 2 has the effect of providing additional aspects, embodiments, claims and formulae in which the definition of is expanded to encompass the following additional options:

[0657] In particular, these additional options are applicable to each of formulas (I'), (I), (II'), (I*), (II**), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), etc.

[0658] Similarly, the variable R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 All of the options, groups, subgroups and combinations provided for R are also included within the scope of the R groups already described with respect to formula (I'). 8 may be applicable to either of formulas (I' and (II'), along with options for

[0659] Throughout this specification, this will be referred to as the variable R as already described with respect to formula (I'). 1 , R 2 , R3 , R 4 , R 5 , R 6 and R 7 One or more definitions of R 8 has the effect of providing additional aspects, embodiments, claims and formulae that apply to either formula (I') or (II') along with options for:

[0660] R 1 Additional options for R in any of a variety of lists, including general and narrower lists, e.g., preferred, more preferred, and most preferred lists. 1 In addition to the options defined herein for 1 Options for may also include: C 1~6 HaloC optionally substituted with alkoxy 1~6 Alkoxy. HaloC as referred to elsewhere in this specification 1~6 The options and preferences for alkoxy apply equally. 1~6 The alkoxy substituent is preferably C 1~3 Alkoxy, more preferably methoxy.

[0661] R 1 Specific additional options for are: [ka]

[0662] R 2 Additional options for R in any of a variety of lists, including general and narrower lists, e.g., preferred, more preferred, and most preferred lists. 2 In addition to the options defined herein for 2 Options for may also include: D.

[0663] Formula (I`) All options, groups, subgroups and combinations provided in relation to formula (I) herein include R 8 The same applies to compounds of formula (I') together with the options mentioned for R. 8 H, D and C 1~6 alkyl. Preferably, R 8 is D. Preferably, R 2 In combination with D, R 8 is D.

[0664] In some embodiments, when falling within the scope of the present claims, the compounds of the present invention do not include: [ka]

[0665] In one embodiment, the present invention provides a compound of formula (I) [ka] (In the formula, A 1 is N or CH, A 2 is N or CH, A 3 is N or CH, provided that A 1 , A 2 , or A 3 at least one of is N, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyloxy, heterocycloalkyl, cycloalkyloxy, or phenoxy is selected from halogen, haloC1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 2 is H or C 1~6 is alkyl, R 3 is H or C 1~6 is alkyl, R 4 is H or a halogen, R 5 is H or a halogen, R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof, [ka] Provides exclusion of:

[0666] Pharmaceutical Compositions and Administration In one embodiment, the present invention provides a pharmaceutical composition comprising a compound of the invention described herein.

[0667] In one embodiment, the present invention provides a pharmaceutical composition comprising a compound of the invention described herein and one or more pharmaceutically acceptable excipients.

[0668] In one embodiment, the present invention provides a pharmaceutical composition further comprising one or more pharmaceutical excipients selected from diluents, fillers, bulking agents, binders, disintegrants, glidants, wetting agents, coatings, emulsifiers or dispersing agents, compression / encapsulation aids, creams or lotions, lubricants, solutions for parenteral administration, materials for chewable tablets, sweeteners or flavoring agents, suspending / gelling agents, and wet granulation agents.

[0669] In certain embodiments, the present invention provides pharmaceutical compositions as described above that are particularly useful for the therapeutic and / or prophylactic treatment of Kv7.2-related disorders, diseases, or disabilities.

[0670] More particularly, the pharmaceutical compositions described herein are useful for the therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease, or disability selected from behavioral disorders, mood disorders, neurodevelopmental disorders, intellectual disabilities, epilepsy, neurodegenerative diseases, pain, migraine, and tinnitus.

[0671] The compound of the present invention can be used as a medicine (for example, in the form of a pharmaceutical preparation).The pharmaceutical preparation can be administered to the body orally (for example, in the form of tablets, coated tablets, sugar-coated tablets, hard gelatin capsules and soft gelatin capsules, solutions, emulsions or suspensions), nasally (for example, in the form of nasal sprays), or rectally (for example, in the form of suppositories).However, administration can also be carried out parenterally, such as intramuscularly or intravenously (for example, in the form of injections).

[0672] The compounds of the present invention can be processed with pharmaceutically inert inorganic or organic adjuvants for the preparation of tablets, coated tablets, sugar-coated tablets, and hard gelatin capsules.Lactose, corn starch or its derivatives, talc, stearic acid or its salts, etc. can be used as adjuvants for tablets, sugar-coated tablets, or hard gelatin capsules, for example.

[0673] Suitable adjuvants for soft gelatin capsules are, for example, vegetable oils, waxes, fats, semisolid substances, or liquid polyols etc.

[0674] Suitable adjuvants for the production of solutions and syrups are, for example, water, polyols, saccharose, invert sugar or glucose etc.

[0675] Suitable adjuvants for injection solutions are, for example, water, alcohols, polyols, glycerol, vegetable oils, etc.

[0676] Suitable adjuvants for suppositories are, for example, natural or hardened oils, waxes, fats, semi-solid or liquid polyols etc.

[0677] In addition, pharmaceutical preparations may contain preservatives, solubilizers, viscosity-increasing substances, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavorings, salts for varying the osmotic pressure, buffers, masking agents or antioxidants, which may also contain other therapeutically valuable substances.

[0678] Dosage can vary within a wide range and will of course be adapted to the individual requirements in each particular case.Generally, for oral administration, the daily dose is about 0.1 mg to 20 mg per kg of body weight, preferably about 0.5 mg to 4 mg per kg of body weight (for example, about 300 mg per person), preferably divided into 1 to 3 individual doses, which, if appropriate, can be, for example, composed of the same amount.However, it is clear that the upper limit given herein can be exceeded if indicated.

[0679] Provided herein is a pharmaceutical composition comprising the compound of the present invention.In some embodiments, pharmaceutical composition comprises one or more pharmaceutically acceptable excipients.The conventional procedure for selecting and preparing suitable pharmaceutical composition is described in, for example, "Pharmaceuticals-The Science of Dosage Form Designs", MEAulton, Churchill Livingstone, 1988, which is incorporated herein by reference in its entirety.

[0680] Further provided is a method for preparing a pharmaceutical composition comprising combining one or more compounds of the invention.

[0681] Further provided is a method for preparing a pharmaceutical composition, comprising combining one or more compounds of the present invention with one or more pharmaceutically acceptable excipients.The pharmaceutical composition can be prepared, for example, by conventional dissolving, mixing, granulating, or coating methods, or combinations thereof. Such pharmaceutically acceptable excipients may include, for example, sugars (e.g., lactose, glucose, sucrose), starches (e.g., corn starch, potato starch), cellulose and its derivatives (e.g., sodium carboxymethylcellulose, ethyl cellulose, cellulose acetate), powdered tragacanth, malt, gelatin, talc, cocoa butter and suppository wax, oils (e.g., peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, soybean oil), glycols (e.g., propylene glycol), polyethylene glycol (PEG), esters (e.g., ethyl oleate, ethyl laurate), agar, buffers (e.g., magnesium hydroxide, aluminum hydroxide), alginic acid, pyrogen-free water, isotonic saline, Ringer's solution, ethyl alcohol, phosphate buffer, non-toxic compatible lubricants (e.g., sodium lauryl sulfate, magnesium stearate), coloring agents, release agents, coating agents, sweeteners, flavoring agents, and fragrances. Preservatives and antioxidants can also be present in the pharmaceutical composition, according to the judgment of the formulator.

[0682] Depending on the intended method of administration, the disclosed pharmaceutical compositions can be in solid, semi-solid, or liquid dosage forms, such as injections, tablets, suppositories, pills, sustained-release capsules, elixirs, tinctures, emulsions, syrups, powders, liquids, suspensions, and the like, and in some cases can be in unit doses consistent with conventional pharmaceutical practice. These methods can include systemic or local administration, such as oral, nasal, parenteral (by intravenous (both bolus and infusion), intramuscular, or subcutaneous injection), transdermal, intravaginal, buccal, rectal, or topical (by powder, ointment, or drops) routes of administration. These methods can also include intracisternal, intraperitoneal, as an oral or nasal spray, or as a liquid aerosol or dry powder pharmaceutical composition for inhalation. In some embodiments, the pharmaceutical compositions provided herein comprise one or more disclosed compounds, their tautomers, and / or pharmaceutically acceptable salts thereof and are for oral administration. In other embodiments, the pharmaceutical compositions are for intravenous administration.

[0683] Oral administration solid dosage forms may include capsules (for example, soft and hard-filled gelatin capsules), tablets, pills, powders and granules.In some embodiments, solid dosage forms may be prepared with one or more coatings and / or shells, such as release-controlling coatings, for example, enteric coatings.Solid dosage forms may be formulated to release one or more disclosed compounds (or their solvates, tautomers or pharmaceutically acceptable salts) solely, or primarily, or preferentially, in a certain part of the digestive tract, optionally in a delayed manner.Solid dosage forms may also include, for example, microencapsulated forms.

[0684] Oral administration liquid dosage forms can include, for example, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs.Such liquid compositions can include, for example, pharmaceutically acceptable excipients, such as water or other solvents, solubilizers, emulsifiers, oils, polyethylene glycols and fatty acid esters, adjuvants, sweeteners, flavorings, or aromatics, or any combination thereof.Injectable pharmaceutical compositions can include, for example, sterile injectable aqueous compositions (for example, solutions, suspensions or emulsions) or oily suspensions.

[0685] Injectable pharmaceutical compositions, in some embodiments, may contain one or more solvents and / or diluents, such as water, Ringer's solution, USP and isotonic sodium chloride solution, sterile fixed oils, fatty acids, or any combination thereof. In some embodiments, injectable pharmaceutical compositions may be prepared as lyophilized powders, for example, lyophilized powders that are mixed with a liquid diluent prior to injection.

[0686] In some embodiments, it may be desirable to prolong the effect of one or more of the compounds disclosed herein or its pharmaceutically acceptable salts from subcutaneous injection or intramuscular injection administration.This delay can be achieved, for example, by using the liquid suspension of crystalline or amorphous material with poor water solubility, or by dissolving or suspending the compound or its solvate, tautomer or pharmaceutically acceptable salts in oily vehicle, or by using the injectable depot form that comprises a microencapsulation matrix that comprises one or more biodegradable polymers.

[0687] Pharmaceutical compositions for rectal or vaginal administration may include suppositories, which may be prepared using suitable non-irritating excipients such as cocoa butter, polyethylene glycol, or a suppository wax, or using fatty emulsions or suspensions.

[0688] Dosage forms for topical or transdermal administration may include, for example, ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. Ophthalmic pharmaceutical compositions and ear drops may also be prepared.

[0689] The pharmaceutical compositions provided herein may be packaged in unit-dose or multi-dose containers, such as sealed ampoules or vials, and may be stored in a freeze-dried (lyophilized) state requiring only the addition of a sterile liquid excipient for injection (e.g., a diluent, carrier, e.g., water) immediately prior to use. Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules, or tablets of the type described herein. Unit-dosage formulations include those containing a daily dose or daily unit sub-dose, or an appropriate fraction thereof, of the active ingredient.

[0690] The subject matter further provides veterinary compositions comprising at least one active ingredient as defined herein together with a veterinary excipient or carrier for the active ingredient. The veterinary excipient or carrier is a substance useful for the purpose of administering the composition and may be a solid, liquid, or gaseous substance that is otherwise inert or acceptable in the veterinary arts and compatible with the active ingredient. These veterinary compositions may be administered parenterally, orally, or by any other desired route.

[0691] medical use The compounds of the present invention described herein or pharmaceutical compositions comprising the same may be useful as medicaments for the therapeutic and / or prophylactic treatment of Kv7.2-associated disorders, diseases or disabilities in subjects in need thereof.

[0692] In one embodiment, the present invention provides a method for therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease, or disability in a subject in need thereof, comprising administering an effective amount of a compound of the present invention described herein or a pharmaceutical composition thereof.

[0693] In one embodiment, the present invention provides a method for therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease, or disability in a subject in need thereof, comprising administering an effective amount of a compound of the present invention described herein or a pharmaceutical composition comprising the same, wherein the pharmaceutical composition further comprises one or more pharmaceutically acceptable excipients.

[0694] In one embodiment, the present invention provides a method for the therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease or disability in a subject in need thereof, comprising administering to a subject a compound of formula (I) [ka] (In the formula, A 1 is N or CH, A 2 is N or CH, A 3 is N or CH, provided that A 1 , A 2 , or A 3 at least one of is N, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 2 is H or C 1~6 is alkyl, R 3 is H or C 1~6 is alkyl, R 4 is H or a halogen, R 5 is H or a halogen, R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0695] In one embodiment, the present invention provides a method for therapeutic and / or prophylactic treatment of a disorder, disease, or disability associated with Kv7.2 in a subject in need thereof, the method comprising a compound of the invention described herein, particularly a compound of formula (I)-(XI), or a solvate or pharmaceutically acceptable salt thereof, any exemplified compound, any embodiment, or a combination of embodiments.

[0696] In one embodiment, the present invention provides a method for therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease, or disability in a subject in need thereof, comprising a compound selected from any of the list of compounds described herein, or a solvate or pharmaceutically acceptable salt thereof.

[0697] In one embodiment, the present invention provides a method for therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease, or disability in a subject in need thereof, comprising a compound selected from Tables 1 and 2, or a solvate or pharmaceutically acceptable salt thereof.

[0698] In one embodiment, the present invention provides a method for therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease, or disability in a subject in need thereof, comprising a compound of Formulae (I) to (XI), or a solvate or pharmaceutically acceptable salt thereof, wherein the Kv7.2-associated disorder, disease, or disability is selected from behavioral disorders, mood disorders, neurodevelopmental disorders, intellectual disabilities, epilepsy, neurodegenerative diseases, pain, migraine, and tinnitus.

[0699] In one embodiment, the present invention provides the above-mentioned method for therapeutic and / or prophylactic treatment of a disorder, disease or disability associated with Kv7.2 in a subject in need thereof, wherein the behavioral disorder is attention deficit hyperactivity disorder (ADHD).

[0700] In one embodiment, the present invention provides a method for therapeutic and / or prophylactic treatment of a disorder, disease or disability associated with Kv7.2 in a subject in need thereof, wherein the mood disorder is depression.

[0701] In one embodiment, the present invention provides a method for therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease or disability in a subject in need thereof, wherein the neurodevelopmental disorder is selected from autism spectrum disorder (ASD) and syndromic developmental disorder.

[0702] In one embodiment, the present invention provides a method for therapeutic and / or prophylactic treatment of a disorder, disease or disability associated with Kv7.2 in a subject in need thereof, wherein the syndromic developmental disorder is selected from Dup15q syndrome (Dup15q), fragile X syndrome (FXS) and Angelman syndrome.

[0703] In one embodiment, the present invention provides a method for therapeutic and / or prophylactic treatment of a disorder, disease, or disability associated with Kv7.2 in a subject in need thereof, wherein the epilepsy is selected from diffuse childhood epilepsy, West syndrome, Ohtahara syndrome, and epileptic encephalopathy.

[0704] In one embodiment, the present invention provides a method for therapeutic and / or prophylactic treatment of a disorder, disease or disability associated with Kv7.2 in a subject in need thereof, wherein the neurodegenerative disease is selected from Alzheimer's disease and motor neuron disease.

[0705] In one embodiment, the present invention provides a method for therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease, or disability in a subject in need thereof, comprising administering an effective amount of a pharmaceutical composition described herein.

[0706] Further provided herein is a compound, solvate, pharmaceutically acceptable salt, or pharmaceutical composition thereof described herein for use as a therapeutically active substance. In one embodiment, the present invention provides a compound of formula (I) as a therapeutically active substance [ka] (In the formula, A 1 is N or CH, A 2 is N or CH, A 3 is N or CH, provided that A 1 , A 2 , or A 3 at least one of is N, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 2 is H or C 1~6 is alkyl, R 3 is H or C 1~6 is alkyl, R 4 is H or a halogen, R 5 is H or a halogen, R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0707] In one embodiment, the present invention provides the use of a compound of the invention described herein, particularly a compound of Formulas (I)-(XI), or a solvate or pharmaceutically acceptable salt thereof, any exemplified compound, any embodiment, or combination of embodiments, as a therapeutically active substance.

[0708] In one embodiment, the present invention provides the use of a compound selected from Tables 1 and 2, or a solvate or pharmaceutically acceptable salt thereof, as a therapeutically active substance.

[0709] In one embodiment, the present invention provides the use of a compound selected from any of the list of compounds described herein, or a solvate or pharmaceutically acceptable salt thereof, as a therapeutically active substance.

[0710] Further provided herein is a compound, solvate, pharmaceutically acceptable salt, or pharmaceutical composition thereof for use in the therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease, or disability in a subject in need thereof.

[0711] In one embodiment, the present invention provides a compound of formula (I) for use in the therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease or disability in a subject in need thereof. [ka] (In the formula, A 1 is N or CH, A 2 is N or CH, A 3 is N or CH, provided that A 1 , A 2 , or A 3 at least one of is N, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 2 is H or C 1~6 is alkyl, R 3 is H or C 1~6 is alkyl, R 4 is H or a halogen, R 5 is H or a halogen, R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C 1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0712] In one embodiment, the present invention provides a compound of the invention as described herein, particularly a compound of formula (I)-(XI), or a solvate or pharmaceutically acceptable salt thereof, any exemplified compound, any embodiment, or combination of embodiments, for use in the therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease, or disability in a subject in need thereof.

[0713] In one embodiment, the present invention provides a compound selected from Tables 1 and 2, or a solvate or pharmaceutically acceptable salt thereof, for use in the therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease, or disability in a subject in need thereof.

[0714] In one embodiment, the present invention provides a compound selected from any of the list of compounds of the present invention for use in the therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease, or disability in a subject in need thereof.

[0715] In one embodiment, the present invention provides a compound of the present invention for use in the therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease, or disability in a subject in need thereof, wherein such disorder, disease, or disability is selected from a behavioral disorder, a mood disorder, a neurodevelopmental disorder, an intellectual disability, epilepsy, a neurodegenerative disease, pain, migraine, and tinnitus.

[0716] In one embodiment, the present invention provides a compound of the present invention for use in the therapeutic and / or prophylactic treatment of a disorder, disease or disability associated with Kv7.2 in a subject in need thereof, wherein the behavioral disorder is attention deficit hyperactivity disorder (ADHD).

[0717] In one embodiment, the present invention provides a compound of the present invention for use in the therapeutic and / or prophylactic treatment of a disorder, disease or disability associated with Kv7.2 in a subject in need thereof, wherein the mood disorder is depression.

[0718] In one embodiment, the present invention provides a compound of the invention for use in the therapeutic and / or prophylactic treatment of a disorder, disease or disability associated with Kv7.2 in a subject in need thereof, wherein the neurodevelopmental disorder is selected from autism spectrum disorder (ASD) and a syndromic developmental disorder.

[0719] In one embodiment, the present invention provides a compound of the invention for use in the therapeutic and / or prophylactic treatment of a disorder, disease or disability associated with Kv7.2 in a subject in need thereof, wherein the syndromic developmental disorder is selected from Dup15q syndrome (Dup15q), Fragile X syndrome (FXS) and Angelman syndrome.

[0720] In one embodiment, the present invention provides a compound of the present invention for use in the therapeutic and / or prophylactic treatment of a disorder, disease or disability associated with Kv7.2 in a subject in need thereof, wherein the epilepsy is selected from diffuse childhood epilepsy, West syndrome, Ohtahara syndrome, and epileptic encephalopathy.

[0721] In one embodiment, the present invention provides a compound of the present invention for use in the therapeutic and / or prophylactic treatment of a disorder, disease, or disability associated with Kv7.2 in a subject in need thereof, wherein the neurodegenerative disease is selected from Alzheimer's disease and motor neuron disease.

[0722] Further provided herein is the use of the compounds of the present invention in the therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease, or disability in a subject in need thereof.

[0723] In one embodiment, the present invention provides a compound of formula (I) for the therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease or disability in a subject in need thereof: [ka] (In the formula, A 1 is N or CH, A 2 is N or CH, A 3 is N or CH, provided that A 1 , A 2 , or A 3 at least one of is N, R 1 Cyano, Halo C 1~6 Alkyl, halogen, 5-membered heteroaryl, C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, 3-6 membered cycloalkylC 0~6 Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC 0~6 alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkylalkoxy, or phenoxy is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 2 is H or C 1~6 is alkyl, R 3 is H or C 1~6 is alkyl, R 4 is H or a halogen, R 5 is H or a halogen, R 6 is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C1~6 Alkyl, 4-6 membered heterocycloalkyl, and haloC 1~6 alkyl, phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R 7 is H, C 1~6 Alkyl, HaloC 1~6 alkyl, and halogen); or a solvate or pharmaceutically acceptable salt thereof.

[0724] In one embodiment, the present invention provides the use of a compound of the invention described herein, particularly a compound of formula (I)-(XI), or a solvate or pharmaceutically acceptable salt thereof, any exemplified compound, any embodiment, or combination of embodiments, for the therapeutic and / or prophylactic treatment of a disorder, disease, or disability associated with Kv7.2 in a subject in need thereof.

[0725] In one embodiment, the present invention provides the use of a compound selected from Tables 1 and 2, or a solvate or pharmaceutically acceptable salt thereof, for the therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease, or disability in a subject in need thereof.

[0726] In one embodiment, the present invention provides the use of a compound selected from any list of compounds described herein, or a solvate or pharmaceutically acceptable salt thereof, for the therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease, or disability in a subject in need thereof.

[0727] In one embodiment, the present invention provides use of a compound of the present invention in the therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease or disability in a subject in need thereof, wherein the Kv7.2-associated disorder, disease or disability is selected from a behavioral disorder, a mood disorder, a neurodevelopmental disorder, an intellectual disability, epilepsy, a neurodegenerative disease, pain, migraine, and tinnitus.

[0728] In one embodiment, the present invention provides the use of a compound of the present invention in the therapeutic and / or prophylactic treatment of a disorder, disease or disability associated with Kv7.2 in a subject in need thereof, wherein the behavioral disorder is attention deficit hyperactivity disorder (ADHD).

[0729] In one embodiment, the present invention provides the use of a compound of the present invention in the therapeutic and / or prophylactic treatment of a disorder, disease or disability associated with Kv7.2 in a subject in need thereof, wherein the mood disorder is depression.

[0730] In one embodiment, the present invention provides use of a compound of the invention in the therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease or disability in a subject in need thereof, wherein the neurodevelopmental disorder is selected from autism spectrum disorder (ASD) and syndromic developmental disorder.

[0731] In one embodiment, the present invention provides use of a compound of the invention in the therapeutic and / or prophylactic treatment of a disorder, disease or disability associated with Kv7.2 in a subject in need thereof, wherein the syndromic developmental disorder is selected from Dup15q syndrome (Dup15q), Fragile X syndrome (FXS) and Angelman syndrome.

[0732] In one embodiment, the present invention provides use of a compound of the present invention in the therapeutic and / or prophylactic treatment of a disorder, disease or disability associated with Kv7.2 in a subject in need thereof, wherein the epilepsy is selected from diffuse childhood epilepsy, West syndrome, Ohtahara syndrome, and epileptic encephalopathy.

[0733] In one embodiment, the present invention provides the use of a compound of the present invention in the therapeutic and / or prophylactic treatment of a disorder, disease, or disability associated with Kv7.2 in a subject in need thereof, wherein the neurodegenerative disease is selected from Alzheimer's disease and motor neuron disease.

[0734] Further provided herein is the use of a compound of the present invention or a pharmaceutical composition comprising the same for ...

Claims

1. Compound of formula (I'): 【Chemistry 1】 (In the formula, A １ is N or CH, A ２ is N or CH, A ３ is N or CH, provided that A １ , A ２ , or A ３ at least one of is N; R １ Cyano, Halo C １～６ Alkyl, halogen, 5-membered heteroaryl, C １～６ Alkyl, C １～６ Alkoxy, HaloC １～６ Alkoxy, 3- to 6-membered cycloalkyl C ０～６ Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC ０～６ alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkyloxy, or phenoxy is selected from halogen, haloC １～６ Alkyl, and haloC １～６ Optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy, haloC １～６ Alkoxy is C １～６ optionally substituted with alkoxy; R ２ H, D, and C １～６ alkyl, R ３ is H or C １～６ is alkyl, R ４ is H or a halogen, R ５ is H or a halogen, R ６ is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C １～６ Alkyl, 4- to 6-membered heterocycloalkyl, and haloC １～６ alkyl, wherein phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC １～６ Alkyl, and haloC １～６ optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R ７ is H, C １～６ Alkyl, haloC １～６ alkyl, and halogen; R ８ H, D, and C １～６ alkyl) or a solvate or pharmaceutically acceptable salt thereof.

2. Compounds of formula (I) 【Chemistry 2】 (In the formula, A １ is N or CH, A ２ is N or CH, A ３ is N or CH, provided that A １ , A ２ , or A ３ at least one of is N; R １ Cyano, Halo C １～６ Alkyl, halogen, 5-membered heteroaryl, C １～６ Alkyl, C １～６ Alkoxy, HaloC １～６ Alkoxy, 3- to 6-membered cycloalkyl C ０～６ Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered heterocycloalkylC ０～６ alkoxy, and phenoxy, wherein heteroaryl, heterocycloalkyl, heterocycloalkyloxy, cycloalkyloxy, or phenoxy is selected from halogen, haloC １～６ Alkyl, and haloC １～６ optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R ２ is H or C １～６ is alkyl, R ３ is H or C １～６ alkyl, R ４ is H or a halogen, R ５ is H or a halogen, R ６ is phenyl, saturated monocyclic 3- to 6-membered cycloalkyl, C １～６ Alkyl, 4- to 6-membered heterocycloalkyl, and haloC １～６ alkyl, wherein phenyl, cycloalkyl, or heterocycloalkyl is selected from halogen, haloC １～６ Alkyl, and haloC １～６ optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy; R ７ is H, C １～６ Alkyl, haloC １～６ alkyl, and halogen) 10. The compound of claim 1, which is: or a solvate or pharmaceutically acceptable salt thereof.

3. (i) A １ (ii) only N, or A ２ (iii) only N is A ３ (iv) only N is A １ and A ２ are both N, or (v) A １ and A ３ and both are N.

4. R １ But, cyano, halo C １～６ Alkyl, halogen, 5-membered heteroaryl, haloC １～６ Alkoxy, 4- to 6-membered heterocycloalkyl, 4- to 6-membered cycloalkylC ０～６ Oxy, and 4- to 6-membered heterocycloalkylC ０～６ 2. The compound of claim 1, wherein the alkoxy group is selected from the group consisting of:

5. R ２ The compound of claim 1 , wherein R 3 is H or D and / or R 3 is H.

6. (i) R ４ and R ５ are both H, or (ii) R ４ and R ５ one of which is H and the other is halogen, or (iii) R ４ and R ５ The compound of claim 1 , wherein both of are halogen.

7. R ６ But, Haro C １～６ Alkyl, phenyl and C ３～６ saturated monocyclic cycloalkyl, wherein the phenyl and C ３～６ saturated monocyclic cycloalkyl is halogen, haloC １～６ Alkoxy, C １～６ Alkyl, and C １～６ 10. The compound of claim 1, optionally substituted with one, two, or three substituents independently selected from alkoxy.

8. R ７ The compound of claim 1 , wherein R 1 is H and / or R 8 is D.

9. (a) A １ is N and A ２ is CH, and A ３ is CH and R １ Halo C １～６ is alkoxy, and R ２ is H and R ３ is H and R ４ and R ５ are both H and R ６ But, Haro C １～６ Alkyl, unsubstituted phenyl, and unsubstituted C ３～６ saturated monocyclic cycloalkyl; R ７ is H and R ８ is H, or (b) A １ is N and A ２ is CH, and A ３ is CH and R １ Halo C １～６ is alkoxy, and R ２ is D and R ３ is H and R ４ and R ５ are both H and R ６ But, Haro C １～６ Alkyl, unsubstituted phenyl, and unsubstituted C ３～６ saturated monocyclic cycloalkyl; R ７ is H and R ８ is D, The compound of claim 1.

10. 10. The compound of claim 1, which is a compound selected from the group consisting of: Table 1

11. The compound of formula (I') is (i) EC ５０ <3 μM, selectivity ratio >10-fold, or (ii) EC ５０ Kv7.2 EC<1 μM, selectivity ratio >30-fold range ５０ 2. A compound of formula (I') according to claim 1, or a solvate or pharmaceutically acceptable salt thereof, which exhibits a Kv7.5_7.3 / Kv7.2 selectivity ratio and / or Kv7.5_7.3 / Kv7.2 selectivity ratio.

12. 10. A compound of formula (I') according to claim 1, or a solvate or pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising said compound, for use in the therapeutic and / or prophylactic treatment of a disorder, disease, or disability associated with Kv7.2 in a subject in need thereof, wherein the disorder, disease, or disability is selected from behavioral disorders, mood disorders, neurodevelopmental disorders, intellectual disabilities, epilepsy, neurodegenerative diseases, pain, migraine, and tinnitus.

13. the disorder, disease, or disability is a behavioral disorder that is attention deficit hyperactivity disorder (ADHD); or the disorder, disease, or disability is a mood disorder that is depression; or the disorder, disease, or disability is a neurodevelopmental disorder selected from autism spectrum disorder (ASD) and a syndromic developmental disorder; or the disorder, disease, or disability is a syndromic developmental disorder selected from Dup15q syndrome (Dup15q), Fragile X syndrome (FXS), and Angelman syndrome; or the disorder, disease, or disability is epilepsy selected from diffuse childhood epilepsy, West syndrome, Ohtahara syndrome, and epileptic encephalopathy; or the disorder, disease, or disability is a neurodegenerative disease selected from Alzheimer's disease and motor neuron disease; 13. A compound or pharmaceutical composition for use according to claim 12.

14. 13. The compound or pharmaceutical composition for use according to claim 12, for systemic or local administration, such as oral, nasal, parenteral (as by intravenous (both bolus and infusion), intramuscular, or subcutaneous injection), transdermal, vaginal, buccal, rectal, or topical modes of administration, as an intracisternal, intraperitoneal, oral or nasal spray, or as a liquid aerosol or dry powder for inhalation.

15. 10. A compound according to claim 1 or a pharmaceutical composition comprising a compound according to claim 1 for use in therapy.

16. 1. A kit for use in the therapeutic and / or prophylactic treatment of a Kv7.2-associated disorder, disease, or disability, comprising: a) a compound according to claim 1 or a pharmaceutical composition comprising a compound according to claim 1; b) Instructions for use and wherein the disorder, disease, or disability associated with Kv7.2 is selected from behavioral disorders, mood disorders, neurodevelopmental disorders, intellectual disabilities, epilepsy, neurodegenerative diseases, pain, migraine, and tinnitus. Includes a kit.

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